Targeting the Dopaminergic System in Autoimmunity

Abstract

Dopamine has emerged as a fundamental regulator of inflammation. In this regard, it has been shown that dopaminergic signalling pathways are key players promoting homeostasis between the central nervous system and the immune system. Dysregulation in the dopaminergic system affects both innate and adaptive immunity, contributing to the development of numerous autoimmune and inflammatory pathologies. This makes dopamine receptors interesting therapeutic targets for either the development of new treatments or repurposing of already available pharmacological drugs. Dopamine receptors are broadly expressed on different immune cells with multifunctional effects depending on the dopamine concentration available and the pattern of expression of five dopamine receptors displaying different affinities for dopamine. Thus, impaired dopaminergic signalling through different dopamine receptors may result in altered behaviour of immunity, contributing to the development and progression of autoimmune pathologies. In this review we discuss the current evidence involving the dopaminergic system in inflammatory bowel disease, multiple sclerosis and Parkinson's disease. In addition, we summarise and analyse the therapeutic approaches designed to attenuate disease development and progression by targeting the dopaminergic system.

Graphical Abstract

Targetting the dopaminergic system in autoimmunity.

Effector T-cells (Teff) orchestrate inflamamtion involved in autoimmunity, whilst regulatory T-cells (Tregs) suppress Teff activity promoting tolerance to self-constituents. Dopamine has emerged as a key regulator of Teff and Tregs function, thereby dopamine receptors have becoming important therapeutic targets in autoimmune disorders, especially in those affecting the brain and the gut, where dopamine levels strongly change with inflammation.

http://bit.ly/2T37TVV

Utilization of venous thromboembolism prophylaxis in American hospitalized pregnant women undergoing cesarean section

Abstract

Background Pregnancy-related venous thromboembolism (VTE) is a leading preventable cause of maternal mortality in the United States; however, American guidelines for pharmacologic VTE prophylaxis remain less aggressive than other developed countries. The Safe Motherhood Initiative (SMI) combines aspects of American and international guidelines to increase utilization of prophylaxis and thereby decrease incidence of pregnancy-related VTE. Objectives To evaluate the prescribing and administration rates of pharmacologic VTE prophylaxis for women undergoing cesarean section (c-section) when retrospectively applying the SMI recommendations. Setting Large academic medical center in Sacramento, California, USA. Method This was a single-center retrospective cohort study of pregnant women undergoing c-section who would have met criteria for pharmacologic prophylaxis according to the SMI. Main outcome measures Prescribing and administration rates of mechanical and pharmacologic VTE prophylaxis. Secondary outcomes included incidence of thromboembolism within 6 weeks after c-section and thromboembolic associated mortality. Results A total of 616 charts were analyzed. When applying the SMI guidelines for VTE prophylaxis, the prescribing rates for mechanical and pharmacologic prophylaxis were 94.3% and 4.71% of patients, respectively, and 94.9% of ordered pharmacologic prophylaxis doses were administered. The incidence of 6-week post-partum VTE was 0.49%. There were no cases of VTE-associated mortality. Conclusion This study demonstrated that a large population of c-section patients fit the SMI criteria for pharmacologic VTE prophylaxis but did not receive it. We observed a 0.49% rate of VTE, which was slightly higher than the nationally reported average rate of 0.3%. With growing rates of pregnancy-associated VTE in the United States, perhaps a more aggressive guideline is warranted.

http://bit.ly/2QYy5ig

Cost-effective analysis of low- versus high-dose colistin in the treatment of multi-drug resistant pneumonia in Saudi Arabia

http://bit.ly/2W6gSXY

Adaptation of a Guide to Equip Employers to Manage the Gradual Return to Work of Individuals with a Musculoskeletal Disorder

Abstract

Purpose The gradual return to work (GRTW) of injured workers poses numerous challenges for workplaces. The aim of this study was to provide employers with an adapted tool to support them in managing GRTWs following a musculoskeletal disorder (MSD), by adapting the Guide for estimation of margin of manoeuvre (Durand et al. in 7th international scientific conference on prevention of work-related musculoskeletal disorders, 2010) and then evaluating the acceptability of the adapted version. Methods A mixed methods design was used. Content experts were surveyed about the content and form of a first version of the adapted tool. Proposed modifications were then discussed in a group meeting until consensus was reached on the changes to be made. The acceptability of the new version was determined by conducting semi-structured interviews of potential users. A thematic analysis of the verbatim transcript was performed. Results Nine experts reached a consensus on 20 modifications, which yielded a tool comprising an instruction guide and a planning worksheet. The eight companies consulted found the tool acceptable, useful, and pertinent, but also identified a few changes to be made. Conclusion The use of original methods made it possible to adapt the content of the tool while taking evidence-based data and user needs into account, all of which contributed to its acceptance. The tool will support employers and standardize management of GRTWs following MSD-related sick leaves. Possible avenues for future research emerged from this study: evaluate the acceptability of new formats and a transdiagnostic version of the tool, and consult workers.

http://bit.ly/2CtXBqF

Site-based adaptation reduces the negative effects of weather upon a southern range margin Welsh black grouse Tetrao tetrix population that is vulnerable to climate change

Abstract

Climate change is an increasing threat to global biodiversity. Whilst there is growing evidence about the potential effectiveness of some aspects of climate change adaptation, the role for site-based management to increase the resilience of vulnerable populations to climate change has been little studied. Here, we test whether such management may reduce the negative effects of unfavourable weather upon a southern range margin Welsh black grouse Tetrao tetrix population that is vulnerable to climate change. The Welsh black grouse recovery programme funded a range of interventions that contributed to a 39% population increase over 10 years. One likely mechanism linking black grouse populations to climate change is the sensitivity of chicks to high June rainfall. We modelled the relationship between June rainfall and management interventions which aimed to increase breeding success (habitat management and lethal predator control) to test whether management could increase the resilience of black grouse populations to such unfavourable weather. Importantly, we found that the negative effect of June rainfall upon productivity was eliminated at sites where predator control occurred, and that productivity was maximised when predator and habitat management were combined. Active management therefore reduced the negative effects of June rainfall upon this vulnerable southern range margin black grouse population, although further work is required to quantify any limits to the success of such management. Active management should be considered as a tool for climate change adaptation in other vulnerable populations, particularly where there is limited potential for species to undergo climate-driven range changes.

http://bit.ly/2W3yTGE

Correction to: Real-World Safety of Intravitreal Bevacizumab and Ranibizumab Treatments for Retinal Diseases in Thailand: A Prospective Observational Study

The Open Access license, which previously read.

http://bit.ly/2W30847

Differential Effects of the Antioxidants N -Acetylcysteine and Pyrrolidine Dithiocarbamate on Mesenchymal Stem Cell Chondrogenesis

Abstract

Introduction

Mesenchymal stem cell (MSC) chondrogenesis is associated with increases in intracellular reactive oxygen species (ROS), which may result in oxidative stress that is detrimental to cartilage regeneration. This study evaluated the ability of the antioxidants N-acetylcysteine (NAC) or pyrrolidine dithiocarbamate (PDTC) to reduce intracellular ROS, and their effect on MSC chondrogenesis and maturation of cartilage-like extracellular matrix.

Methods

Equine bone marrow MSCs were cultured in serum-supplemented chondrogenic medium with or without NAC or PDTC. ROS was quantified in monolayer after 8 and 72 h of culture. MSCs were seeded into agarose, cultured for 15 days, and analyzed for viable cell density, glycosaminoglycan (GAG) and hydroxyproline accumulation, and collagen gene expression. PDTC cultures were evaluated for oxidative damage by protein carbonylation, and mechanical properties via compressive testing.

Results

NAC significantly lowered levels of ROS after 8 but not 72 h, and suppressed GAG accumulation (70%). In secondary experiments using serum-free medium, NAC significantly increased levels of ROS at 72 h, and lowered cell viability and extracellular matrix accumulation. PDTC significantly reduced levels of ROS (~ 30%) and protein carbonylation (27%), and enhanced GAG accumulation (20%). However, the compressive modulus for PDTC-treated samples was significantly lower (40%) than controls. Gene expression was largely unaffected by the antioxidants.

Conclusions

NAC demonstrated a limited ability to reduce intracellular ROS in chondrogenic culture, and generally suppressed accumulation of extracellular matrix. Conversely, PDTC was an effective antioxidant that enhanced GAG accumulation, although the concomitant reduction in compressive properties is a significant limitation for cartilage repair.

http://bit.ly/2RDs1Ru

Editorial Board of Biological Cybernetics: Advances in Computational Neuroscience

http://bit.ly/2MpXfWN

Frailty and Drug Safety at Older Ages

http://bit.ly/2RAaZ6Y

Predicting cerebral edema in ischemic stroke patients

Abstract

Objectives

To produce a scoring system for predicting the development of edema in ischemic stroke patients without edema on admission.

Methods

This retrospective study included 572 ischemic stroke patients (73.3 ± 13.0 years, 300 male) without signs of cerebral edema on the first CT scan, which was performed on admission. Another scan was normally performed 3 days later, and subsequently whenever needed. Edema was defined as cerebral hypodensity with compression of lateral ventricles. The main clinical, laboratory, and instrumental variables obtained during the first 24 h were related to the appearance of edema on the CT scans performed after the first one.

Results

Cerebral edema occurred in 158 patients (27.6%) after a median time of 4 days. The variables independently associated with edema development were (odds ratio, 95% CI) the following: (1) total anterior circulation syndrome (4.20, 2.55–6.93; P < 0.0001), (2) hyperdense appearance of middle cerebral artery (4.12, 2.03–8.36; P = 0.0001), (3) closed eyes (2.53, 1.39–4.60; P = 0.002), (4) vomiting (3.53, 1.45–8.60; P = 0.006), (5) lacunar cerebral syndrome (0.36, 0.17–0.77; P = 0.008); and (6) white matter lesions (0.53, 0.33–0.86; P = 0.01). Counting one positive point for the first four variables and one negative point for the last two variables, a scoring system (E-score) was built. Cerebral edema could be predicted when the score was ≥ 1 (positive predictive value 61.6%, specificity 85.3%, sensitivity 62.0%). The area under the receiver operating characteristic curve was 0.78.

Conclusions

In ischemic stroke patients, six variables obtained during the first 24 h of hospitalization were predictive of subsequent cerebral edema development.

http://bit.ly/2RFHrVL

Association of Bariatric Surgery Status with Reduced HER2+ Breast Cancers: a Retrospective Cohort Study

Abstract

Background

Bariatric surgery is associated with a reduced risk of developing certain malignancies, particularly in women. However, the impact of bariatric surgery on tumor characteristics, cancer treatment, and oncologic outcomes is unknown.

Method

In a retrospective cohort study, 42 subjects diagnosed with breast cancer after bariatric surgery (1989–2014) were matched to 84 subjects with breast cancer (1984–2012) who did not undergo bariatric surgery, based on age, body mass index (BMI), and menopausal status at the time of breast cancer diagnosis, as well as the date of cancer diagnosis. Medical records were reviewed for cancer and bariatric endpoints. Statistical analysis was performed using mixed effects regression models, generalized estimating equation, conditional logistic regression, and Fisher's exact tests.

Results

Women who developed breast cancer after bariatric surgery presented at an earlier stage compared to non-operated, obese controls. In the bariatric surgery group, there were fewer tumors with human epidermal growth factor receptor 2 overexpression (HER2+) (OR 0.16 (0.03–0.76); p = 0.02), with no significant differences seen in estrogen and progesterone receptor positivity. No HER2+ cancers were found in patients who underwent Roux-en-Y gastric bypass (OR 0.00 (0.00–0.43); p = 0.002). On multivariate analysis, bariatric surgery status remained associated with reduced HER2+ breast cancers (OR 0.18 (0.03–0.99); p < 0.05). At a mean follow-up of 5 years, bariatric surgery was associated with trends toward reduced cancer-specific and all-cause mortality.

Conclusions

Bariatric surgery is associated with reduced HER2+ breast cancers, suggesting that bariatric surgery can influence breast cancer characteristics and, potentially, tumor biology.

http://bit.ly/2R0TN5s

Transfer of a minimally invasive mitral valve repair program from a high-volume center to a very low volume center: how many cases are necessary to maintain acceptable results?

Abstract

Objective

To investigate whether minimally invasive mitral valve repair (MIMVR) can be transferred from a high-volume center into a very small volume center and to clarify how many cases are necessary for maintenance of this program, early outcomes of MIMVR in Asahikawa Medical University were compared with those results in patients operated by a single surgeon in Duesseldorf University Hospital.

Methods

Sixty-five patients who underwent MIMVR in Asahikawa Medical University (group A) between May 2014 and July 2018 and 134 patients who underwent MIMVR in Duesseldorf University Hospital (group D) between September 2009 and January 2014 by a surgeon who started MIMVS later in Asahikawa were retrospectively analyzed.

Results

In group D, there were more patients with ischemic mitral valve regurgitation and with annular calcification than in group A. Survival rate at 6 months and 1 year was 98.5% and 98.5% in group A and 92.9% and 91.3% in group D, respectively. EuroSCORE II was significantly higher in patients dead within 30 days and within the first year.

Conclusions

The present study demonstrated that MIMVR programs can be transferred with acceptable early results into very low volume centers, if the team is developed by surgeons who are well trained and experienced in MIMVR. Moreover, the present study suggested that case number for maintenance of acceptable results may be obviously less than the previous recognition that this kind of specialized surgery could be maintained with at least 50 cases annually. However, meticulous preparations for surgery are essential for satisfactory surgical outcomes.

http://bit.ly/2CxObuj

Preoperative biopsy does not affect postoperative outcomes of resectable non-small cell lung cancer

Abstract

Objectives

Preoperative diagnostic interventions such as transbronchial biopsy and/or computed tomography-guided biopsy inevitably disrupt the lung structures and may disseminate tumour cells into the airway, vessels, or pleural cavity. Therefore, these procedures may affect the postoperative outcomes. Thus, we aimed to compare the survival outcomes in patients diagnosed by transbronchial biopsy vs computed tomography-guided biopsy vs lung resection.

Methods

In a single-institution retrospective analysis, data from consecutive patients with cTanyN0M0 lung cancer, who underwent surgery between January 2006 and December 2012, were extracted by chart review. The overall and recurrence-free survivals of patients diagnosed by transbronchial biopsy, computed tomography-guided biopsy, and lung resection were compared using the univariate and multivariate Cox proportional hazard models. A stepwise backward elimination method, with a probability level of 0.15, was used to select the most powerful sets of outcome predictors.

Results

Transbronchial biopsy and/or computed tomography-guided biopsy were performed for larger and more advanced tumours, than lung resection (intra- or postoperative-diagnosis group). At crude analysis, transbronchial biopsy group and computed tomography-guided biopsy group showed higher probability of pleural dissemination, and worse prognosis than the lung resection group. At multivariate analysis, the diagnostic methods were not identified as independent risk factors of pleural dissemination, overall survival, or recurrence-free survival.

Conclusions

Preoperative diagnostic interventions did not affect the relapse risk and prognosis, in this study cohort. Thus, preoperative diagnostic intervention is recommended if deemed necessary.

http://bit.ly/2CrUJum

Lung transplantation via cardiopulmonary bypass: excellent survival outcomes from extended criteria donors

Abstract

Objectives

The role of intraoperative cardiopulmonary bypass (CPB) in lung transplant (LTx) surgery is controversial. CPB enables slow pulmonary reperfusion and initial ventilation with low oxygen concentrations, both theoretically protective of transplanted lungs. In this study, we explored clinical outcomes following extended criteria donor LTx surgery implementing a thoroughly protective allograft reperfusion strategy using CPB.

Methods

Thirty-nine consecutive adult patients who underwent bilateral LTx with elective CPB and protective allograft reperfusion were reviewed. Bilaterally implanted lungs were reperfused simultaneously, via slow CPB flow reduction and initial ventilation with 21% oxygen and nitric oxide, followed by a brief modified ultrafiltration. During weaning from CPB, mean pulmonary arterial pressure was strictly maintained at 10–15 mmHg by controlling CPB and pulmonary flow. The clinical outcomes in 23 patients who received lungs from extended criteria donors (ECD group) were elucidated and compared to 16 patients undergoing LTx from standard criteria donors (SCD group).

Results

No life-threatening deterioration was observed to graft functionality during the first 72 h after LTx in the ECD group; however, only one patient required post-transplant extracorporeal membrane oxygenation. In three of 23 ECD LTx patients (12%), surgical revision for bleeding was required. Survival outcomes for the ECD group were favorable, with 100% survival at 6-months, 87.0% at 1-year, and 80.7% at 5-years. Outcomes in the ECD group were comparable to those in the SCD group.

Conclusions

Despite a certain extent of risk associated with full-dose heparinization, use of CPB does not undermine survival outcomes after ECD LTx surgery if protective allograft reperfusion is securely performed.

http://bit.ly/2RDPy52

Reoperation for postoperative bleeding following pulmonary resection: a report of a single-center experience

Abstract

Objective

The variety and incidence of postoperative complications seem to have changed with recent progress in thoracic surgery. This study attempted to improve our recognition of postoperative bleeding.

Methods

Among 1143 patients undergoing pulmonary resection for pulmonary nodules, ten underwent surgical treatment for postoperative bleeding. Clinical and pathologic data were analyzed. Additionally, the relationship between the bleeding point and an increased amount of drained bloody effusion before the second operation was analyzed.

Results

The bleeding point was recognized in eight cases: the intercostal artery (n = 4), the lung (n = 2), aberrant vessel of the apex of the lung (n = 1) and the bronchial artery (n = 1). The bleeding points were unknown in two cases in whom the decision to perform a second operation was delayed. Potential reasons or influential factors for bleeding were stapling complications (n = 4), low coagulation ability (n = 2) and intraoperative injury (n = 1). We experienced two cases in which intercostal arterial bleeding was induced by scratching the thoracic wall or the vertebra with the edge of the reinforced stapling line or the sharp edge of a broken staple at the first operation. We divided patients into three groups based on the interval between operations. Bleeding from the arteries seemed to show a higher rate of bleeding per hour than that from the lung parenchyma.

Conclusion

The bleeding points and speculated reasons for bleeding varied among patients. We were able to cure all ten cases. It might be dependent on the rapid decision of reoperation in cases with arterial bleeding was suspected.

http://bit.ly/2RDhlCo

Return to work after surgical treatment for malignant pleural mesothelioma: report of a case

Abstract

We report the case of a 56-year-old woman who underwent pleural biopsy to identify the cause of the right pleural effusion. The pathological diagnosis was epithelial malignant pleural mesothelioma. The patient worked as a junior high school teacher and strongly hoped for continuing work. Thus, we performed pleurectomy/decortication (P/D) as a curative surgery. The operative findings showed pleural thickening that in the lower lobe of the lung. Thus, peeling of the lower lobe was performed. Pleural biopsy was only performed on the upper and middle lobes. As a result, the operation was limited P/D. The pathological findings showed a small number of mesothelioma cells in the upper and middle lobes. The patient received four courses of cisplatin plus pemetrexed systemic chemotherapy after surgery. Continuous maintenance chemotherapy using pemetrexed has been performed until the time of writing. At present, she has continued her work for 6 years after the operation and has extended her retirement age without recurrence.

http://bit.ly/2CxzCqv

Total surgical repair for secondary aortoesophageal fistula: two case reports

Abstract

We present two consecutive patients with secondary aortoesophageal fistula (AEF) who successfully underwent total repair including partial esophagectomy, removal of infected vascular prosthesis, graft replacement, and esophageal reconstruction using gastric tube concomitant to omental wrapping for staged operation in short phase. One 81-year-old male who had undergone thoracic endovascular aortic repair and another 69-year-old male who had undergone graft replacement of the descending thoracic aorta were referred to our hospital for treatment of AEF. In the first operation, partial esophagectomy, removal of infected vascular prosthesis, and graft replacement were performed via left rib-cross thoracotomy. About half a day after the operation when the patients became hemodynamically stable, esophageal reconstruction was started. The gastric tube was prepared via median laparotomy and introduced to the left thoracic cavity with the omentum through the enlarged hiatus. Thereafter, the gastric tube was anastomosed to the oral side of the esophageal stump via left thoracotomy with the same wound similar to the first operation. Finally, the graft positioned parallel to the gastric tube was completely wrapped by the omentum. Both patients could ingest orally 4 weeks after surgery and maintained no recurrence of infection.

http://bit.ly/2RDpuXM

Outcomes and predictive factors for pathological node-positive in radiographically pure-solid, small-sized lung adenocarcinoma

Abstract

Objectives

The indication of limited resection for radiographically pure-solid, small-sized lung adenocarcinoma is controversial. This study aimed to reveal the long-term outcome of standard surgical treatment and determine the predictive factors for pathological lymph node metastasis in optimal candidates undergoing limited surgical resection for pure-solid, small-sized lung adenocarcinoma.

Methods

The medical records of 107 consecutive patients were retrospectively reviewed at our hospital between December 2002 and December 2013. Inclusion criteria were histopathological diagnosis of lung adenocarcinoma, radiographically pure-solid tumor, ≤ 2 cm tumor size measured using thin-section computed tomography, clinical N0M0, patients who underwent lobectomy with systematic or lobe-specific lymph node dissection, and R0 resection. Overall and disease-free survival curves were calculated using the Kaplan–Meier method. Clinicopathological factors predicting pathological node-positive metastasis were identified by univariate and multivariate analysis.

Results

The 5-year overall and disease-free survival rates were 91.4% and 87.3%, respectively. Multivariate analysis demonstrated maximum standardized uptake value > 5 as the independent predictor of pathological node-positive metastasis (odds ratio 3.81; 95% confidence interval 1.25–12.3; p = 0.02). In all patients, the pathological node-positive rate was 16.7%; in patients who had a maximum standardized uptake value of ≤ 5, the rate was 7.9%.

Conclusion

The long-term outcome of standard surgical treatment was favorable. Maximum standardized uptake value was a significant predictor of pathological node-positive metastasis; however, diagnostic accuracy was not favorable. Therefore, the selection of optimal candidates is difficult, and limited surgical resection may not be applicable in pure-solid, small-sized lung adenocarcinoma.

http://bit.ly/2Ctbeqa

Correction to: Positive correlation between sarcopenia and elevation of neutrophil/lymphocyte ratio in pathological stage IIIA (N2-positive) non-small cell lung cancer patients

In the original publication of the article, the title was incorrectly published as "Positive correlation between sarcopenia and elevation of neutrophil/lymphocyte ratio in pathological stage.

http://bit.ly/2RFwnHV

Our tips for bronchoplasty using suture holder and tourniquet

Abstract

Bronchial anastomosis is an important part of successful bronchoplasty, but it takes time to achieve stable results because of few opportunities to do it. To ensure a stable outcome, we have applied some tips for bronchial anastomosis. One of the tips is the use of a suture holder to obtain appropriate suture pitches, adjusting the discrepancy of the bronchial diameter, and another one is the use of a tourniquet to obtain an adequate tension upon tying the knots, ensuring good operative view.

http://bit.ly/2CtM2Qi

Pulmonary artery reconstruction using an autologous pulmonary vein patch in pulmonary resection

Abstract

Pulmonary artery (PA) reconstruction has been accepted to avoid pneumonectomy in locally advanced lung cancer surgery because of its satisfactory outcomes with regard to long-term survival and its low postoperative morbidity and mortality rates. Several techniques of PA reconstruction have been documented. However, the availability of PA reconstruction using an autologous pulmonary vein (PV) patch is unclear. Here, we present a patient who successfully underwent PA reconstruction using an autologous PV patch during resection of a lung adenocarcinoma (cT2aN1M0: stage IIB) in the left upper lobe with hilar extension and left main PA invasion.

http://bit.ly/2RDYAPx

Clinical analysis of pneumonectomy for destroyed lung: a retrospective study of 32 patients

Abstract

Objective

Destroyed lung is whole lung destruction secondary to chronic or recurrent lung infections. This clinical condition can result in irreversible changes in the lung parenchyma. In this study, we aimed to evaluate patients undergoing pneumonectomy with a diagnosis of lung destruction in terms of surgical technique, post-operative morbidity and mortality, and long-term outcomes.

Methods

A total of 32 patients that underwent pneumonectomy due to a destroyed lung between 2005 and 2017 were retrospectively reviewed. Age, gender, presenting symptoms, etiologies, localization of the destruction, pre-operative medical history, pre- and post-operative respiratory function tests, intraoperative complications and bleeding volume, morbidity and mortality, length of hospital stay, and long-term follow-up outcomes were reviewed for each patient.

Results

The study included 32 patients with a mean age of 31.7 ± 10.8 years. All the patients presented with persistent cough, whereas sputum production was presented by 25, hemoptysis by 18, and chest pain by 11 patients. The underlying primary diseases included nonspecific bronchiectasis in 20 (62.5%), tuberculosis in 9 (28.1%), left pulmonary hypoplasia accompanied by Bochdalek hernia in 2 (6.2%), and aspiration of a foreign body lodged in the left main bronchus in 1 (3.1%) patient. Mean operative time was 220.6 ± 40.2 min and mean perioperative bleeding was 450.9 ± 225.7 ml. Post-operative complications occurred in 14.2% of the patients, most commonly including atelectasis associated with stasis of secretions and wound site infection. Mean post-operative hospital stay was 11.8 ± 2.8 days and mean follow-up period was 35.5 ± 28.3 months. A significant clinical improvement was observed in 81.2% of the patients post-operatively.

Conclusions

Favorable long-term outcomes were obtained in our patients through careful patient selection and appropriate pre-operative work-up and surgical technique.

http://bit.ly/2CFOfZ9

Two cases of air leak syndrome after bone marrow transplantation successfully treated by the pleural covering technique

Abstract

Air leak syndrome (ALS) is a rare complication after bone marrow transplantation (BMT) and usually has a fatal outcome because of the high recurrence rate and treatment-refractory nature. A 32-year-old man with a history of BMT for acute lymphoblastic leukemia suffered from metachronous bilateral ALS. Bullectomy and the pleural covering procedure (PLC) were successfully performed for each side of the thorax. After surgery, no relapse of pneumothorax was seen for 2 years on the right side and for 1 year on the left side. A 38-year-old man with a history of BMT for acute myelogenous leukemia (AML) suffered from ALS at the thorax on the left side. Bullectomy and the PLC were successfully performed. After that no recurrence of left pneumothorax for 7 years. We experienced two cases of ALS after BMT successfully treated by the PLC. This technique may be a viable treatment option for future lung transplantation.

http://bit.ly/2Ry4UrL

Comparative efficacy of ivabradine versus beta-blockers in patients with mitral stenosis in sinus rhythm: systematic review and meta-analysis

Abstract

Background Patients with mitral valve stenosis have increased heart rate. HR reduction is known as an important treatment and therapy strategy for patients with mitral valve stenosis. Aim of the review The aim of this systematic review and meta-analysis was to compare the efficacy of ivabradine versus beta-blockers in patients with mitral stenosis in sinus rhythm. Methods Randomized controlled trials were searched in Cochrane Library, PubMed, Web of Science, CRD, Scopus, and Google Scholar with no start time limitation and ending June 2018. Risk of bias across was assessed by the Cochrane Risk of Bias Assessment tool. Fixed effects models were used to combine the results and the mean difference with a 95% confidence interval. This meta-analysis was performed using Meta Package in R software. Results Five studies entered meta-analysis. The total number of patients treated with ivabradine and beta-blockers was 178 and 178 respectively. The results showed that the mean of maximum HR and HR at rest was lower at about 5.03 units and upper 4.32 units respectively with use of ivabradine compared with the use of beta-blockers. These values were statistically significant. Conclusion It seems that the efficacy of ivabradine is good in comparison with betablockers, but it still requires more clinical trials.

http://bit.ly/2T3QhZJ

Evaluation of anxiety and depression scales and quality of LIFE in cervical dystonia patients on botulinum toxin therapy and their relatives

Abstract

Objective

In this study, quality of life and psychiatric comorbid disorders were investigated in patients with cervical dystonia and their spouses and we also investigated the effect of botulinum toxin (BTX) treatment on these parameters.

Material and method

Thirty patients with cervical dystonia (CD) on BTX treatment and their spouses (n = 30) were included. Beck Depression Scale (BDS), State-Trait Anxiety Inventory I and II (STAI-I, STAI-II), Hospital Anxiety Scale (HAS), Hospital Depression Scale (HDS) for psychiatric comorbid disease assessment, Toronto Western Spasmodic Torticollis Scale (TWSTRS) for disease activity assessment, and Craniocervical Dystonia Questionnaire (CDQ-24), Cervical Dystonia Impact Profile (CDIP-58), and Short Form 36 (SF-36) questionnaires for quality of life assessment were used. BDS, STAI-I and STAI-II, HAS, HDS, and SF-36 scales were also obtained from the spouses. The same tests were applied both before and 8 weeks after the BTX treatment.

Conclusion

In our study, an increase in psychiatric comorbid disorders such as depression and anxiety was observed and the quality of life was adversely affected in all areas in patients. In the spouses of the patients, the rates of psychiatric comorbid disorders such as depression and anxiety were found to be increased when compared to healthy subjects while vitality, mental health, and general health perception were found to be negatively affected.

Patients showed improvements in anxiety level, disease activity, and overall quality of life scales after BTX treatment.

http://bit.ly/2DkoJdn

Follow-up score, change score or percentage change score for determining clinical important outcome following surgery? An observational study from the Norwegian registry for Spine surgery evaluating patient reported outcome measures in lumbar spinal stenosis and lumbar degenerative spondylolisthesis

Abstract

Background

Assessment of outcomes for spinal surgeries is challenging, and an ideal measurement that reflects all aspects of importance for the patients does not exist. Oswestry Disability Index (ODI), EuroQol (EQ-5D) and Numeric Rating Scales (NRS) for leg pain and for back pain are commonly used patients reported outcome measurements (PROMs). Reporting the proportion of individuals with an outcome of clinical importance is recommended. Knowledge of the ability of PROMs to identify clearly improved patients is essential. The purpose of this study was to search cut-off criteria for PROMs that best reflect an improvement considered by the patients to be of clinical importance.

Methods

The Global Perceived Effect scale was utilized to evaluate a clinically important outcome 12 months after surgery. The cut-offs for the PROMs that most accurately distinguish those who reported 'completely recovered' or 'much improved' from those who reported 'slightly improved', unchanged', 'slightly worse', 'much worse', or 'worse than ever' were estimated. For each PROM, we evaluated three candidate response parameters: the (raw) follow-up score, the (numerical) change score, and the percentage change score.

Results

We analysed 3859 patients with Lumbar Spinal Stenosis [(LSS); mean age 66; female gender 50%] and 617 patients with Lumbar Degenerative Spondylolisthesis [(LDS); mean age 67; 72% female gender]. The accuracy of identifying 'completely recovered' and 'much better' patients was generally high, but lower for EQ-5D than for the other PROMs. For all PROMs the accuracy was lower for the change score than for the follow-up score and the percentage change score, especially among patients with low and high PROM scores at baseline.

The optimal threshold for a clinically important outcome was ≤24 for ODI, ≥0.69 for EQ-5D, ≤3 for NRS leg pain, and ≤ 4 for NRS back pain, and, for the percentage change score, ≥30% for ODI, ≥40% for NRS leg pain, and ≥ 33% for NRS back pain. The estimated cut-offs were similar for LSS and for LDS.

Conclusion

For estimating a 'success' rate assessed by a PROM, we recommend using the follow-up score or the percentage change score. These scores reflected a clinically important outcome better than the change score.

http://bit.ly/2MhIJAc

Effects of spinal manipulative therapy biomechanical parameters on clinical and biomechanical outcomes of participants with chronic thoracic pain: a randomized controlled experimental trial

Abstract

Background

Spinal manipulative therapy (SMT) includes biomechanical parameters that vary between clinicians, but for which the influence on the therapy clinical effects is unknown. This parallel-randomized controlled trial aimed to investigate the effect of SMT biomechanical parameters on the outcomes of participants with chronic thoracic pain (CTP) following three treatment sessions (follow-up at one week).

Methods

Adults reporting CTP (pain within the evaluated region [T6 to T8] for ≥3 months) were asked to participate in a four-session trial. At the first session, participants were randomly assigned to one of three experimental groups (different SMT doses) or the control group (no SMT). During the first three sessions, one SMT was executed at T7 for the experimental groups, while a 5-min rest was provided to the control group. SMT were delivered through an apparatus using a servo-controlled linear actuator motor and doses consisted of peak forces, impulse durations, and rates of force application set at 135 N, 125 ms and 920 N/s (group 1), at 250 N, 125 ms and 1840 N/s (group 2), and at 250 N, 250 ms, 920 N/s (group 3). Disability and pain intensity were evaluated at each session (primary outcomes). Spinal stiffness was assessed before-and-after each SMT/rest and at follow-up. Tenderness and muscle activity were evaluated during each spinal stiffness trial. Improvement was evaluated at follow-up. Differences in outcomes between groups and sessions were evaluated as well as factors associated with clinical improvement.

Results

Eighty-one participants were recruited and 17, 20, 20 participants of the three experimental groups and 18 of the control group completed the protocol. In exception of higher pain intensity at baseline in the control group, no between-group differences were found for any of the outcomes. A decrease in pain intensity, disability, spinal stiffness, and tenderness during spinal stiffness were observed (p-values< 0.05). At follow-up, 24% of participants were classified as 'improved'. Predictors of improvement were a greater decrease in pain intensity and in tenderness (p-values< 0.05).

Conclusions

In an experimental setting, the delivery of a SMT does not lead to significantly different outcomes in participants with CTP than a control condition (spinal stiffness assessment). Studies are still required to explore the mechanisms underlying SMT effects.

Trial registration

ClinicalTrials.gov NCT03063177, registered 24 February 2017).

http://bit.ly/2RAZiNl

Influence of seasonal changes on disease activity and distribution of affected joints in rheumatoid arthritis

Abstract

Background

Previous studies suggest that RA activity is sensitive to seasonal changes. This study explored the influence of season on RA activity, particularly the distribution of affected joints, using a nationwide database in Japan.

Methods

We investigated 12,839 patients whose RA activity was recorded in spring (n = 3250), summer (n = 916), fall (n = 1021), and winter (n = 7652). Disease activity score (DAS) 28-CRP, simplified disease activity index (SDAI), and clinical disease activity index (CDAI) were used as indices of disease activity. Disease activity was also assessed according to DAS28-CRP scores (remission, low, moderate, or high). The affected joint distribution was investigated using novel joint indices (x, y, z), where x and y are indices for the upper and lower joints, respectively, and z is the index for large joint predominance.

Results

Mean DAS28-CRP and median SDAI and CDAI scores were highest in spring and lowest in fall. There was a significant difference in the DAS28-CRP for fall versus spring and winter. Fall was associated with a higher remission rate, and spring and winter with high and moderate RA activity, respectively. Significant differences in x, y, SDAI, and CDAI scores were found for spring versus summer, fall, and winter, in addition to fall versus winter (except in y). There was no seasonal difference in the z index.

Conclusions

RA activity in the upper and lower extremities may be highest in spring, followed by winter. Seasonal changes should be considered in patients with RA to better understand their symptoms.

http://bit.ly/2CvxAXU

Subcostal approach to anterior quadratus lumborum block for pain control following open urological procedures

Abstract

In the case of open urological surgeries, analgesic coverage at mid thoracic dermatomal levels is required. As shown in cadaveric studies, the site of QL block injection is an important determinant of the extent of dye spread and presumably local anesthetic dermatomal coverage. In this case series, we evaluated dermatomal blockade and analgesic efficacy of a subcostal approach to anterior QL block following open urological surgeries. Twenty-two adult patients undergoing renal transplant surgery (60%) and open nephrectomy (40%) received unilateral ultrasound-guided subcostal anterior QL block with catheter insertion. Sensory level, pain score (numeric rating scale, NRS), local anesthetic consumption, and opioid consumption (morphine equivalent dose, MED) were assessed daily for 3 days. The block achieved sensory blockade between T6-7 and L1-2. The most frequently affected dermatomes were T8 -T12 and the number of blocked segments was 3 (mean 2.8). The median (interquartile range Q1, Q3) of NRS pain score was 3.7 (2.8–5.5), 3.3 (2.4–4.7), 2.9 (1.9–3.6), and 2.3 (1.0–4.2) on POD0, POD1, POD2, and POD3, respectively. Our preliminary data showed that the subcostal approach to anterior QL block provides appropriate thoracic dermatome level needed for analgesia following open urological surgical procedures between T6-7 and L1-2.

http://bit.ly/2CrDaKW

Fabrication of mesoporous SiO 2 @SLS composite to remove organic pollutants: hydrogen bond-induced intriguing changes of solubility

Abstract

Because biomass lignin shows good adsorption activity, its derivatives such as alkali lignin and kraft lignin have been applied in water treatment; however, sodium lignosulfonate (SLS), mainly limited by its high water solubility, is not applicable in this respect. In this work, we fabricated SiO₂@SLS mesoporous adsorbent using a facile solution coating method by one step. SLS coating SiO₂ enables the former to be "separated" from water, accomplishing the soluble to insoluble conversion. This change makes the composite more suitable and efficient to remove organic pollutants from water than the SLS precursor. It is found that interfacial hydrogen bonds play a significant role in the conversion, which is further corroborated by density functional theory calculations. Various characterizations show that SiO₂@SLS is composed of uniform particles around 80 nm in size. Abundant mesopores with diameters ranging from 2 to 3 nm are found on the surface of SiO₂@SLS nanoparticles. The specific surface areas of SiO₂@SLS were measured between 293.4 and 33.2 m² g⁻¹, depending on the SLS amount used in the preparing process. Originating from the bio-adsorbent lignin precursor, the SiO₂@SLS composite shows excellent adsorption property. Representatively, SiO₂@SLS-0.6 is able to efficiently remove methylene blue (MB), almost twice as much as SiO₂-0 does; its adsorption capacity (Q_m) reaches 206.2 mg g⁻¹ according to the Langmuir model fitting; notably, SiO₂@SLS-0.6 works very well even in a high-concentration MB solution (50 mg L⁻¹), showing removal efficiencies at 90.0% (within 1 h) and 99.9% (720 h, i.e., 30 days). Plus having remarkable adsorption stability, our composite SiO₂@SLS is anticipated to be promising in application of polluted water treatment.

Graphical abstract

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http://bit.ly/2HfDjGW

Tuberous Breast Deformity Correction: 12-Years Experience

http://bit.ly/2Cvu1kF

Prediction of Long Term Restenosis Risk After Surgery in the Carotid Bifurcation by Hemodynamic and Geometric Analysis

Abstract

This study explored the potential of hemodynamic disturbances and geometric features to predict long-term carotid restenosis after carotid endarterectomy (CEA). Thirteen CEA for carotid diameter stenosis > 70% were performed with patch graft (PG) angioplasty in nine cases, and primary closure (PC) in four cases. MRI acquisitions within one month after CEA were used for hemodynamic and geometric characterization. Personalized computational hemodynamic simulations quantified the exposure to low and oscillatory wall shear stress (WSS). Geometry was characterized in terms of flare (the expansion at the bulb) and tortuosity. At 60 months after CEA, Doppler ultrasound (DUS) was applied for restenosis detection and intima-media thickness determination. Larger flares were associated to larger exposure to low WSS (Pearson R² values up to 0.38, P < 0.05). The two cases characterized by the highest flare and the largest low WSS exposure developed restenosis > 50% at 60 months. Linear regressions revealed associations of DUS observations of thickening with flare variables (up to R²= 0.84, P < 0.001), and the exposure to low (but not oscillatory) WSS (R²= 0.58, P < 0.05). Our findings suggest that arteriotomy repair should avoid a large widening of the carotid bulb, which is linked to restenosis via the generation of flow disturbances. Hemodynamics and geometry-based analyses hold potential for (1) preoperative planning, guiding the PG vs. PC clinical decision, and (2) stratifying long-term restenosis risk after CEA.

http://bit.ly/2HmMy8j

A Mechanistic Analysis of Possible Blood Transfusion Failure to Increase Circulatory Oxygen Delivery in Anemic Patients

Abstract

The effects of changing hematocrit (Hct) on the rate of circulatory oxygen ( \(\hbox {O}_2\) ) delivery were modeled analytically to describe transfusion of 0.5–3.0 units of packed red blood cells (pRBC, 300 mL/unit, 60% Hct) to anemic patients. In our model, Hct affects \(\hbox {O}_2\) delivery to the microcirculation by changing blood \(\hbox {O}_2\) carrying capacity and blood viscosity, which in turn affects blood flow velocity and, therefore, \(\hbox {O}_2\) delivery. Changing blood velocity impacts the \(\hbox {O}_2\) delivery by affecting the oxygen diffusive losses as blood transits through the arteriolar vasculature. An increase in Hct has two opposite effects: it increases the blood \(\hbox {O}_2\) carrying capacity and decreases the flow velocity. This suggests the existence of an optimal Hct that maximizes \(\hbox {O}_2\) delivery. Our results show that maximal \(\hbox {O}_2\) delivery occurs in the anemic range, where \(\text {Hct} < 39\) %. Optimal blood management is associated with transfusing enough units up to reaching maximal \(\hbox {O}_2\) delivery. Although somewhat complex to implement, this practice would result in both substantial blood savings and improved \(\hbox {O}_2\) delivery.

http://bit.ly/2RTdu3K

Does movement matter in people with back pain? Investigating ‘atypical’ lumbo-pelvic kinematics in people with and without back pain using wireless movement sensors

Abstract

Background

Interventions for low back pain (LBP) commonly target 'dysfunctional' or atypical lumbo-pelvic kinematics in the belief that correcting aberrant movement improves patients' pain and activity outcomes. If atypical kinematic parameters and postures have a relationship to LBP, they could be expected to more prevalent in people with LBP compared to people without LBP (NoLBP). This exploratory study measured, defined and compared atypical kinematic parameters in people with and without LBP.

Methods

Wireless inertial motion and EMG sensors were used to measure lumbo-pelvic kinematics during standing trunk flexion (range of motion (ROM), timing, sequence coordination, and extensor muscle activation) and in sitting (relative sitting position, pelvic tilt range) in a sample of 126 of adults without LBP and 140 chronic LBP subjects. Atypical movement was defined using the 10th/90th centiles of the NoLBP group. Mean differences and prevalence rates for atypical movement were calculated. Dichotomised pain scores for 'high-pain-on-bending' and 'high-pain-on-sitting' were tested for their association with atypical kinematic variables.

Results

For standing flexion, significant mean differences, after adjusting for age and gender factors, were seen for the LBP group with (i) reduced ROM (trunk flexion (NoLBP 111^o, LBP 93^o, p < .0001), lumbar flexion (NoLBP 52^o, LBP 46^o, p < .0001), pelvic flexion (NoLBP 59^o, LBP 48^o, p < .0001), (ii) greater extensor muscle activation for the LBP group (NoLBP 0.012, LBP 0.25 p < .0001), (iii) a greater delay in pelvic motion at the onset of flexion (NoLBP − 0.21 s; LBP − 0.36 s, p = 0.023), (iv) and longer movement duration for the LBP group (NoLBP 2.28 s; LBP 3.18 s, p < .0001). Atypical movement was significantly more prevalent in the LBP group for small trunk (× 5.4), lumbar (× 3.0) and pelvic ROM (× 3.9), low FRR (× 4.9), delayed pelvic motion at 20^o flexion (× 2.9), and longer movement duration (× 4.7). No differences between groups were seen for any sitting parameters. High pain intensity was significantly associated with small lumbar ROM and pelvic ROM.

Conclusion

Significant movement differences during flexion were seen in people with LBP, with a higher prevalence of small ROM, slower movement, delayed pelvic movement and greater lumbar extensor muscle activation but without differences for any sitting parameter.

http://bit.ly/2Hsxvu2

Predictors of Steroid Hormone Concentrations in Early Pregnancy: Results from a Multi-Center Cohort

Abstract

Objectives To identify factors predicting maternal sex steroid hormone concentrations in early pregnancy. Methods The Infant Development and the Environment Study recruited healthy pregnant women from academic medical centers in four US cities. Gold standard liquid chromatography–tandem mass spectrometry was used to measure maternal sex steroids concentrations (total testosterone [TT], free testosterone [FT], estrone [E1], estradiol [E2], and estriol [E3] concentrations) in serum samples from 548 women carrying singletons (median = 11.7 weeks gestation). Women completed questionnaires on demographic and lifestyle characteristics. Results In multivariable linear regression analyses, hormone concentrations varied in relation to maternal age, body mass index (BMI), race, and parity. Older mothers had significantly lower levels of most hormones; for every year increase in maternal age, there was a 1–2% decrease in E1, E2, TT, and FT. By contrast, each unit increase in maternal BMI was associated 1–2% lower estrogen (E1, E2, E3) levels, but 1–2% higher androgen (TT, FT) concentrations. Hormone concentrations were 4–18% lower among parous women, and for each year elapsed since last birth, TT and FT were 1–2% higher (no difference in estrogens). Androgen concentrations were 18–30% higher among Black women compared to women of other races. Fetal sex, maternal stress, and lifestyle factors (including alcohol and tobacco use) were not related to maternal steroid concentrations. Conclusions for Practice Maternal demographic factors predict sex steroid hormone concentrations during pregnancy, which is important given increasing evidence that the prenatal endocrine environment shapes future risk of chronic disease for both mother and offspring.

http://bit.ly/2T0MqwL

Predictors of Steroid Hormone Concentrations in Early Pregnancy: Results from a Multi-Center Cohort

Abstract

Objectives To identify factors predicting maternal sex steroid hormone concentrations in early pregnancy. Methods The Infant Development and the Environment Study recruited healthy pregnant women from academic medical centers in four US cities. Gold standard liquid chromatography–tandem mass spectrometry was used to measure maternal sex steroids concentrations (total testosterone [TT], free testosterone [FT], estrone [E1], estradiol [E2], and estriol [E3] concentrations) in serum samples from 548 women carrying singletons (median = 11.7 weeks gestation). Women completed questionnaires on demographic and lifestyle characteristics. Results In multivariable linear regression analyses, hormone concentrations varied in relation to maternal age, body mass index (BMI), race, and parity. Older mothers had significantly lower levels of most hormones; for every year increase in maternal age, there was a 1–2% decrease in E1, E2, TT, and FT. By contrast, each unit increase in maternal BMI was associated 1–2% lower estrogen (E1, E2, E3) levels, but 1–2% higher androgen (TT, FT) concentrations. Hormone concentrations were 4–18% lower among parous women, and for each year elapsed since last birth, TT and FT were 1–2% higher (no difference in estrogens). Androgen concentrations were 18–30% higher among Black women compared to women of other races. Fetal sex, maternal stress, and lifestyle factors (including alcohol and tobacco use) were not related to maternal steroid concentrations. Conclusions for Practice Maternal demographic factors predict sex steroid hormone concentrations during pregnancy, which is important given increasing evidence that the prenatal endocrine environment shapes future risk of chronic disease for both mother and offspring.

http://bit.ly/2T0MqwL

Learned Helplessness After Anterior Cruciate Ligament Reconstruction: An Altered Neurocognitive State?

Abstract

Traumatic knee injuries, such as anterior cruciate ligament (ACL) sprains, have detrimental effects on long-term health as they initiate a cycle of chronic pain, physical inactivity, and disability. Alterations in strength and neural activity are factors that contribute to rehabilitation failure after ACL reconstruction (ACLR); however, psychological deficits also hinder rehabilitative success. Neural impairments observed following injury and ACLR may be associated with psychological dysfunction, a phenomenon defined as learned helplessness (LH). The proposed framework establishes the link between depressed neural activity and psychological dysfunction after ACL injury using foundational evidence from neuroscience and psychology to support the integration of LH into recovery.

http://bit.ly/2S0gyew

Impact of Ad Libitum Versus Programmed Drinking on Endurance Performance: A Systematic Review with Meta-Analysis

Abstract

Background

Debate continues on how athletes should hydrate during exercise. Several studies have recently been published comparing the effect of ad libitum (ALD) and programmed drinking (PD) on endurance performance (EP).

Objective

This work examined whether one drinking strategy offers an EP advantage over the other.

Design

Systematic review and meta-analysis of crossover controlled trials.

Data Sources

PubMed and SPORTDiscus database searches.

Eligibility Criteria for Selecting Studies

Key criteria were (1) experiments performed under controlled settings; (2) exercise lasting ≥ 1 h; (3) exercise initiated in an euhydrated state; (4) fluid intake during PD > ALD; (5) fluid composition matched for electrolytes; and (6) carbohydrate intake varied by > 25% between conditions when the exercise was 1 h and matched for exercise > 1 h.

Results

Seven publications, producing eight effect estimates, including cycling and running exercises and representing 82 subjects, were included. Mean (± standard deviation) ambient temperature, exercise intensity and duration of the experiments were 28 ± 6 °C, 81 ± 12% of maximal heart rate and 96 ± 25 min, respectively. Mean rate of fluid consumption for the PD and ALD conditions was 1073 ± 247 mL/h and 505 ± 156 mL/h, respectively. Mean change in body mass for the PD and ALD conditions was − 1.0 ± 0.5% and − 2.1 ± 0.7%, respectively. Compared with PD, ALD improved EP by 0.98 ± 0.44% (95% confidence interval 0.11–1.84%). The greater EP conferred by ALD is likely trivial.

Conclusions

Despite ALD being associated with an hourly rate of fluid consumption half as much as PD, and resulting in a dehydration level considered sufficient to impair EP, both strategies were found to similarly impact 1–2 h cycling or running performances conducted at moderate to high intensity and under temperate to warm ambient conditions.

http://bit.ly/2HkgMca

Revised Approach to the Role of Fatigue in Anterior Cruciate Ligament Injury Prevention: A Systematic Review with Meta-Analyses

Abstract

Background

Causes of anterior cruciate ligament (ACL) injuries are multifactorial. Anterior cruciate ligament injury prevention should thus be approached from a multifactorial perspective as well. Training to resist fatigue is an underestimated aspect of prevention programs given that the presence of fatigue may play a crucial role in sustaining an ACL injury.

Objectives

The primary objective of this literature review was to summarize research findings relating to the kinematic and kinetic effects of fatigue on single-leg landing tasks through a systematic review and meta-analysis. Other objectives were to critically appraise current approaches to examine the effects of fatigue together with elucidating and proposing an optimized approach for measuring the role of fatigue in ACL injury prevention.

Methods

A systematic literature search was conducted in the databases PubMed (1978–November 2017), CINAHL (1992–November 2017), and EMBASE (1973–November 2017). The inclusion criteria were: (1) full text, (2) published in English, German, or Dutch, (3) healthy subjects, (4) average age ≥ 18 years, (5) single-leg jump landing task, (6) evaluation of the kinematics and/or kinetics of the lower extremities before and after a fatigue protocol, and (7) presentation of numerical kinematic and/or kinetic data. Participants included healthy subjects who underwent a fatigue protocol and in whom the effects of pre- and post-fatigue on three-dimensional lower extremity kinematic and kinetics were compared. Methods of data collection, patient selection, blinding, prevention of verification bias, and study design were independently assessed.

Results

Twenty studies were included, in which four types of single-leg tasks were examined: the single-leg drop vertical jump, the single-leg drop landing, the single-leg hop for distance, and sidestep cutting. Fatigue seemed to mostly affect initial contact (decreased angles post-fatigue) and peak (increased angles post-fatigue) hip and knee flexion. Sagittal plane variables at initial contact were mostly affected under the single-leg hop for distance and sidestep cutting conditions whilst peak angles were affected during the single-leg drop jump.

Conclusions

Training to resist fatigue is an underestimated aspect of prevention programs given that the presence of fatigue may play a crucial role in sustaining an ACL injury. Considering the small number of variables affected after fatigue, the question arises whether the same fatigue pathways are affected by the fatigue protocols used in the included laboratory studies as are experienced on the sports field.

http://bit.ly/2RWtAJN

The Muscle Protein Synthetic Response to Meal Ingestion Following Resistance-Type Exercise

Abstract

Protein ingestion following resistance-type exercise stimulates muscle protein synthesis rates and consequently enhances the skeletal muscle adaptive response to prolonged training. Ingestion of ~ 20 g of quickly digestible protein isolate optimizes muscle protein synthesis rates during the first few hours of post-exercise recovery. However, the majority of daily protein intake is consumed as slower digestible, nutrient-rich, whole-food protein sources as part of mixed meals. Therefore, the muscle protein synthetic response to the ingestion of protein supplements and typical foods or mixed meals may differ substantially. In addition, the muscle protein synthetic response to feeding is not only determined by acute nutrient intake but is also likely modulated by habitual energy and nutrient intake and nondietary factors such as habitual physical activity, body composition, age, and/or sex. Therefore, nutritional recommendations to maximize the muscle protein synthetic response to exercise depend on the type of meal (e.g., protein supplements vs. mixed meals) and the time until the next feeding opportunity (e.g., feeding before overnight sleep) and, therefore, need to be personalized to the individual athlete.

http://bit.ly/2HkCZXo

DEFEAT-polypharmacy: deprescribing anticholinergic and sedative medicines feasibility trial in residential aged care facilities

Abstract

Background Prolonged use of anticholinergic and sedative medicines is correlated with worsening cognition and physical function decline. Deprescribing is a proposed intervention that can help to minimise polypharmacy whilst potentially improving several health outcomes in older people. Objective This study aimed to examine the feasibility of implementing a deprescribing intervention that utilises a patient-centred pharmacist-led intervention model; in order to address major deprescribing challenges such as general practitioner time constraints and lack of accessible deprescribing guidelines and processes. Setting Three residential care facilities. Methods The intervention involved a New Zealand registered pharmacist utilising peer-reviewed deprescribing guidelines to recommend targeted deprescribing of anticholinergic and sedative medicines to GPs. Main outcome measure The change in the participants' Drug Burden Index (DBI) total and DBI 'as required' (PRN) was assessed 3 and 6 months after implementing the deprescribing intervention. Results Seventy percent of potential participants were recruited for the study (n = 46), and 72% of deprescribing recommendations suggested by the pharmacist were implemented by General Pratitioners (p = 0.01; Fisher's exact test). Ninety-six percent of the residents agreed to the deprescribing recommendations, emphasising the importance of patient centred approach. Deprescribing resulted in a significant reduction in participants' DBI scores by 0.34, number of falls and adverse drug reactions, 6 months post deprescribing. Moreover, participants reported lower depression scores and scored lower frailty scores 6 months after deprescribing. However, cognition did not improve; nor did participants' reported quality of life. Conclusion This patient-centred deprescribing approach, demonstrated a high uptake of deprescribing recommendations and success rate. After 6 months, significant benefits were noted across a range of important health measures including mood, frailty, falls and reduced adverse reactions. This further supports deprescribing as a possible imperative to improve health outcomes in older adults.

http://bit.ly/2AU4uBt

Sarecycline: First Global Approval

Abstract

Sarecycline (Seysara™) is an oral, once-daily, tetracycline-class drug for which a tablet formulation is approved in the USA for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients aged ≥ 9 years. The drug was developed by Paratek and Allergen and later acquired by Almirall S.A. (a Barcelona-based pharmaceutical company focused on medical dermatology). Sarceycline tablets were approved in early October 2018 and are planned to be available for patients in January 2019. Sarecycline capsules have also been studied in the USA, but no recent reports of development have been identified for this formulation. There are currently no clinical trials underway assessing sarecycline in rosacea. This article summarizes the milestones in the development of sarecycline leading to this first approval for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris.

http://bit.ly/2W14GrD

Current and Emerging Treatment Strategies for Graves’ Orbitopathy

Abstract

Graves' orbitopathy is a debilitating disorder which occurs in patients with autoimmune thyroid disease, mainly Graves' disease, and adds layers of complexity to management of both conditions. We conducted a comprehensive review of literature for publications relating to established and new management options for Graves' orbitopathy and have summarized key articles in this review. Initial evaluation of patients with Graves' disease should also include clinical evaluation for orbitopathy. If eye disease is present, patients are best managed by a multi-specialty team including an endocrinologist and ophthalmologist. All patients with Graves' orbitopathy benefit from risk factor modification and normalization of thyroid function tests. Patients with active, mild disease generally benefit from local therapies and selenium, while patients with moderate-to-severe disease usually require the addition of intravenous glucocorticoid therapy. If there is an inadequate response to glucocorticoid therapy, several second-line therapies have been investigated for use, including orbital radiotherapy (with additional glucocorticoids), rituximab, cyclosporine, mycophenolate mofetil, and methotrexate. Use of new biologic agents, mainly teprotumumab and tocilizumab, have demonstrated impressive reductions in disease activity and severity. If these results are confirmed, the treatment paradigm is likely to change in the future. Finally, there are several novel immunotherapies being investigated for Graves' disease, which may have treatment implications for Graves' orbitopathy as well. Overall, there are many encouraging advances in the therapy of Graves' orbitopathy that are making the future more promising for patients suffering from this disease.

http://bit.ly/2QWhAU3

Hydrochlorothiazid und nichtmelanozytärer Hautkrebs

http://bit.ly/2FI3943

Psychoonkologie in dermatologischen Praxen

Zusammenfassung

Hintergrund

Im nationalen Krebsplan ist eine psychoonkologische Betreuung fester Bestandteil einer umfassenden Betreuung von Krebspatienten. Dieses Ziel ist auch im Strategiepapier der Nationalen Versorgungskonferenz Hautkrebs enthalten. In zertifizierten Hautkrebszentren konnten die wesentlichen Voraussetzungen für eine psychoonkologische Versorgung geschaffen werden. Ein großer Anteil von Hautkrebspatienten wird jedoch in dermatologischen Praxen versorgt. Für dieses Versorgungssegment liegen bisher keine Daten zur psychoonkologischen Versorgung vor.

Material und Methoden

In einer deskriptiven Querschnittstudie in Form eines schriftlichen Surveys wurden niedergelassene Dermatologen zur psychoonkologischen Versorgung von Hautkrebspatienten im Erhebungszeitraum Oktober 2016 bis Februar 2017 befragt.

Ergebnisse

Den psychoonkologischen Fragebogen haben 171 Praxen beantwortet; 19,4 % der Praxen gaben einen onkologischen Schwerpunkt an. Die mittlere Anzahl jährlich betreuter Hautkrebspatienten wurde mit 554,3 ± 659,1 und die der Melanompatienten mit 62,4 ± 73,6 angegeben. Ein Großteil der Praxiskollegen schätzt den Anteil psychoonkologisch betreuungsbedürftiger Patienten gering ein (≤5 %). In 21,9 % der Praxen wird über psychoonkologische Unterstützungsangebote aktiv informiert; 26,1 % der Praxen kooperieren bezüglich psychoonkologischer Unterstützungsangebote mit anderen Einrichtungen; 29,3 % der Praxen haben Interesse an einem psychoonkologischen Versorgungskonzept.

Diskussion

In dermatologischen Praxen ist nur von gelegentlicher und teils defizitärer psychoonkologischer Versorgung und einer Zuweisung zu psychoonkologischen Einrichtungen auszugehen. Dies zeigt die Notwendigkeit einer Sensibilisierung für das Thema, um eine Integration der psychoonkologischen Beratung auch in der dermatologischen Routineversorgung zu ermöglichen.

http://bit.ly/2FyObOv

Luftverschmutzung und atopisches Ekzem

Zusammenfassung

Hintergrund

Unter zahlreichen Risikofaktoren für die Entstehung eines atopischen Ekzems (AE) wird neuerdings der Einfluss von Luftverschmutzung vermehrt diskutiert. Ein systematisches Review hierzu liegt aber bisher nicht vor.

Fragestellung

Welche Effekte von Außenluftverschmutzung (Partikel, Stickstoffoxide, Schwefeldioxid, Ozon oder allgemeine Straßenverkehrsemissionen) auf AE zeigen sich in einer systematischen Analyse verfügbarer umweltepidemiologischer Studien?

Methodik

Alle umweltepidemiologischen Studien zu AE und Luftverschmutzung aus der Literaturdatenbank PubMed wurden identifiziert, ihre wichtigsten Kenngrößen tabellarisch zusammengefasst, qualitativ nach Evidenzgraden beurteilt und beschrieben.

Ergebnisse

Es wurden 57 entsprechende Studien identifiziert. Nur in einer der 15 Querschnittstudien, bei denen die Exposition großräumig erfasst wurde, zeigte sich ein signifikanter Zusammenhang zwischen AE und Luftverschmutzung. Dagegen fanden sich signifikante positive Assoziationen von AE mit straßenverkehrsbedingten Emissionen – insbesondere aus LKWs – in 23 von 30 Studien mit kleinräumiger Expositionserfassung. Von diesen 30 Studien waren 14 Kohortenstudien (1-mal Erwachsene, 13-mal Geburtskohorten). Die einzige Kohortenstudie bei Erwachsenen zeigte eine Assoziation insbesondere mit einem intrinsischen AE. In ostasiatischen Geburtskohorten (alle in den letzten 3 Jahren veröffentlicht) war eine Verkehrsbelastung der Mutter während der Schwangerschaft mit einer erhöhten Inzidenz von AE beim Kind assoziiert. In den älteren Kohortenstudien aus Europa/USA war dies nicht so klar oder wurde nicht untersucht. In 5/5 Panelstudien (alle aus Korea) fand sich ein positiver Zusammenhang zwischen dem Schweregrad von Ekzem und der Außenluftbelastung.

Schlussfolgerung

In der systematischen Analyse umweltepidemiologischer Studien zeigte sich eine eher gute Evidenz dafür, dass Belastungen mit Straßenverkehrsemissionen, die kleinräumig variieren, die Prävalenz von AE erhöhen, während großräumige Belastung mit groben Partikeln (PM10) oder SO₂ keinen Einfluss zeigte. Unter pathophysiologischen Aspekten scheinen Verkehrsemissionen sowohl über Einflüsse auf die Hautbarriere als auch auf die Aktivierung von Immunreaktionen zu wirken.

http://bit.ly/2FJ5UlO

Continuous Glucose Monitoring: A Brief Review for Primary Care Practitioners

Abstract

Glycated hemoglobin A1c (HbA1c) is routinely used as a marker of average glycemic control, but it fails to provide data on hypoglycemia and glycemic variability, both of which are associated with adverse clinical outcomes. Self-monitoring of blood glucose (SMBG), particularly in insulin-treated patients, is a cornerstone in the management of patients with diabetes. SMBG helps with treatment decisions that aim to reduce high glucose levels while avoiding hypoglycemia and limiting glucose variability. However, repeated SMBG can be inconvenient to patients and difficult to maintain in the long term. By contrast, continuous glucose monitoring (CGM) provides a convenient, comprehensive assessment of blood glucose levels, allowing the identification of high and low glucose levels, in addition to evaluating glycemic variability. CGM using newer detection and visualization systems can overcome many of the limitations of an HbA1c-based approach while addressing the inconvenience and fragmented glucose data associated with SMBG. When used together with HbA1c monitoring, CGM provides complementary information on glucose levels, thus facilitating the optimization of diabetes therapy while reducing the fear and risk of hypoglycemia. Here we review the capabilities and benefits of CGM, including cost-effectiveness data, and discuss the potential limitations of this glucose-monitoring strategy for the management of patients with diabetes.

Funding

Sanofi US, Inc.

http://bit.ly/2RyAN3x

Development of a novel model for predicting survival of patients with spine metastasis from colorectal cancer

Abstract

Objective

To develop a novel nomogram for predicting survival of patients with spine metastasis from colorectal cancer (SMCRC) based on the clinical characteristics and prognostic factors.

Methods

Included in this study were 93 SMCRC patients who received treatments in our institute between 2006 and 2017, whose clinical data were analyzed retrospectively by univariate and multivariate analysis to identify independent variables that could predict prognosis. A nomogram for survival prediction was established on the basis of preoperative independent factors, and then subjected to bootstrap re-samples for internal validation. The discrimination was measured by concordance index (C-index). We used ROC analysis with the corresponding AUROC to compare the prediction accuracy of Changzheng Nomogram with three existing prognostic systems (Tomita, Tokuhashi and Bauer).

Results

The high and median degrees of primary tumor differentiation, primary tumor surgery, carcinoembryonic antigen ≤ 5 ng/ml, no visceral metastases and ECOG-PS (0–2) were favorable prognostic factors for CRC metastases in the spine. These five preoperative independent factors were identified and entered into the nomogram with the C-index of 0.786 (0.739–0.833). The calibration curves for probability of 12- and 24-month overall survival (OS) showed good agreement between the predictive risk and the actual risk, and calibration was assessed. Compared with the previous prognostic systems, Changzheng Nomogram reported in this study showed higher accuracy in predicting OS of patients with SMCRC spinal metastases (p < 0.05).

Conclusion

By using this novel predictive model, clinicians could more precisely estimate the survival outcome of individual patients by evaluating clinical characteristics and identify subgroups of patients who are in need of a specific individual treatment strategy.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

http://bit.ly/2FIOhm3

Management des lokal fortgeschrittenen Zervixkarzinoms

Zusammenfassung

Das lokal fortgeschrittene Zervixkarzinom erfordert eine besonders intensive interdisziplinäre Absprache. In der Definition des Stadiums spielen neben der klassischen FIGO-Einteilung (FIGO: „Fédération Internationale de Gynécologie et d'Obstétrique") Risikofaktoren eine wichtige Rolle. Dabei ist der Lymphknotenstatus entscheidend. In frühen Stadien wird operativ vorgegangen, bei weiter fortgeschrittener Erkrankung bis hin zum Stadium IVA wird die Radiochemotherapie präferiert. In jedem Fall ist eine frühzeitige Besprechung innerhalb eines Tumorboards erforderlich. Kontroversen betreffen z. B. den Einsatz moderner bildgebender Verfahren, die Therapie bei befallenen paraaortalen Lymphknoten, den Stellenwert einer neoadjuvanten Chemotherapie und die Versuche, die klassische Radiochemotherapie mit Cisplatin zu intensivieren. Der Artikel gibt dazu einen Überblick, unter besonderer Berücksichtigung aktueller Studiendaten und unter Bezugnahme auf die derzeit gültigen Leitlinien.

http://bit.ly/2QXptZf

Tailoring the Microstructure in Polycrystalline Co–Ni–Ga High-Temperature Shape Memory Alloys by Hot Extrusion

Abstract

Co–Ni–Ga alloys represent a new class of promising high-temperature shape memory alloys allowing realization of functional components for applications at elevated temperatures. Single crystals show a fully reversible pseudoelastic response at temperatures up to 500 °C. However, for most industrial applications, the application of polycrystalline material is needed. Polycrystalline Co–Ni–Ga alloys suffer from the anisotropic properties inherent to shape memory alloys, i.e., a strong orientation dependence of transformation strains, and therefore, are prone to intergranular fracture. This drawback can be curtailed by using appropriately textured material with a favorable grain-boundary orientation distribution. The current study discusses the impact of a hot-extrusion process on microstructural evolution and functional properties of polycrystalline Co–Ni–Ga high-temperature shape memory alloys paving the way to their robust application.

http://bit.ly/2AQzrXq

A closed-form single-pose calibration method for the camera–projector system

Abstract

To improve the calibration efficiency of the structured light stereo vision system, a closed-form single-pose calibration method is proposed. Previous works calibrate the structured light stereo vision system via the planar-based method since the world coordinates of the projected pixels are easy to find. But the disadvantage of these methods is that multiple poses are required, so that the mechanical movement is necessary in these calibration methods. In this paper, the inherent geometry between the spheres and their image is exploited deeply. Thus, a sphere-based calibration method is proposed. The proposed method first calibrates the camera from the image of the absolute conic through an improved algorithm. Then, the three-dimensional coordinates of the projected pixels are found via the inherent geometrical relation. Next, the projector is calibrated using the direct linear method. Finally, the distortion of the projector is found through the nonlinear optimization method with an improved updating direction. Experiments demonstrate that not only the calibration efficiency is improved, but also the calibration accuracy is improved.

http://bit.ly/2B2e8SX

Classification and comparison of on-line video summarisation methods

Abstract

Many methods exist for generating keyframe summaries of videos. However, relatively few methods consider on-line summarisation, where memory constraints mean it is not practical to wait for the full video to be available for processing. We propose a classification (taxonomy) for on-line video summarisation methods based upon their descriptive and distinguishing properties such as feature space for frame representation, strategies for grouping time-contiguous frames, and techniques for selecting representative frames. Nine existing on-line methods are presented within the terms of our taxonomy and subsequently compared by testing on two synthetic data sets and a collection of short videos. We find that success of the methods is largely independent of techniques for grouping time-contiguous frames and for measuring similarity between frames. On the other hand, decisions about the number of keyframes and the selection mechanism may substantially affect the quality of the summary. Finally, we remark on the difficulty in tuning the parameters of the methods "on-the-fly", without knowledge of the video duration, dynamic or content.

http://bit.ly/2T8NHla

Associations Between Maternity Care Practices and 2-Month Breastfeeding Duration Vary by Race, Ethnicity, and Acculturation

Abstract

Objectives This study examines the associations between specific maternity care practices and breastfeeding duration for Spanish-speaking Hispanic, English-speaking Hispanic, non-Hispanic Native American, and non-Hispanic White women. Methods We analyzed data from the 2012–2014 New Mexico Pregnancy Risk Assessment Monitoring System. We used survey language as a proxy measure of acculturation and categorized women as Spanish-speaking Hispanic, English-speaking Hispanic, non-Hispanic Native American, and non-Hispanic White. We conducted bivariate analyses to compare rates of breastfeeding at 2 months and experiences of maternity care practices and logistic regression analysis to estimate the effects of these practices on breastfeeding duration for each group. Results Hispanic women were less likely than non-Hispanic women to breastfeed for at least 2 months (67.9% vs. 76.6%; p = 0.000); however, this varied significantly by acculturation level: 78.1% of Spanish-speaking Hispanic women compared to 66.1% of English-speaking Hispanic women breastfed for at least 2 months (p = 0.000). The effects of specific maternity care practices on duration varied across groups. Among non-Hispanic White, Native American, and English-speaking Hispanic women, breastfeeding while at the hospital had the strongest effect (AOR 2.09, 95% CI 1.67–2.61; AOR 2.71, 95% CI 2.08–3.52; and AOR 1.99, 95% CI 1.76–2.25, respectively). Among Spanish-speaking Hispanic women, being encouraged to breastfeed on demand had the strongest effect (AOR 5.179, 95% CI 3.86–6.94). Conclusions for Practice The effects of maternity care practices on breastfeeding duration vary by race, ethnicity, and acculturation level. Health care systems must acknowledge the diversity of their patient populations when seeking to develop and implement breastfeeding-friendly practices.

http://bit.ly/2SZRZLS

Associations Between Maternity Care Practices and 2-Month Breastfeeding Duration Vary by Race, Ethnicity, and Acculturation

Abstract

Objectives This study examines the associations between specific maternity care practices and breastfeeding duration for Spanish-speaking Hispanic, English-speaking Hispanic, non-Hispanic Native American, and non-Hispanic White women. Methods We analyzed data from the 2012–2014 New Mexico Pregnancy Risk Assessment Monitoring System. We used survey language as a proxy measure of acculturation and categorized women as Spanish-speaking Hispanic, English-speaking Hispanic, non-Hispanic Native American, and non-Hispanic White. We conducted bivariate analyses to compare rates of breastfeeding at 2 months and experiences of maternity care practices and logistic regression analysis to estimate the effects of these practices on breastfeeding duration for each group. Results Hispanic women were less likely than non-Hispanic women to breastfeed for at least 2 months (67.9% vs. 76.6%; p = 0.000); however, this varied significantly by acculturation level: 78.1% of Spanish-speaking Hispanic women compared to 66.1% of English-speaking Hispanic women breastfed for at least 2 months (p = 0.000). The effects of specific maternity care practices on duration varied across groups. Among non-Hispanic White, Native American, and English-speaking Hispanic women, breastfeeding while at the hospital had the strongest effect (AOR 2.09, 95% CI 1.67–2.61; AOR 2.71, 95% CI 2.08–3.52; and AOR 1.99, 95% CI 1.76–2.25, respectively). Among Spanish-speaking Hispanic women, being encouraged to breastfeed on demand had the strongest effect (AOR 5.179, 95% CI 3.86–6.94). Conclusions for Practice The effects of maternity care practices on breastfeeding duration vary by race, ethnicity, and acculturation level. Health care systems must acknowledge the diversity of their patient populations when seeking to develop and implement breastfeeding-friendly practices.

http://bit.ly/2SZRZLS

Trocar Site Hernias in Bariatric Surgery—an Underestimated Issue: a Qualitative Systematic Review and Meta-Analysis

Abstract

The reported incidence of trocar site hernias in bariatric surgery ranges between 0.5 and 3%. The best available evidence derives from retrospective studies analysing prospective databases, thus including only patients who presented with symptoms or received surgical treatment due to trocar site hernias after a laparoscopic bariatric procedure. A systematic literature research was conducted up until September 2017. Search strategies included proper combinations of the MeSH terms 'laparoscopy' and 'bariatric surgery', 'trocar/port' and 'hernia'. Searches were not limited by publication type or language. The review was registered in PROSPERO (ID 85102) and performed according to the PRISMA guidelines. Sixty-eight publications were included. Pooled hernia incidence was 3.22 (range 0–39.3%). Thirteen trials reported systematic closure of the fascia; 12 trials reported no closure. Data availability did not allow for pooling to calculate relative risk. Higher BMI and specific hernia examination using imaging modalities were associated with a significantly higher incidence of trocar site hernias. Studies dedicated to detection of TsH reported a pooled incidence of 24.5%. Trocar site hernias are an underestimated complication of minimally invasive multiportal bariatric surgery. While high-quality trials are not available allowing for a precise calculation of the incidence, existing data are indicative of very high incidence rates. Risk factors for developing a trocar site hernia in bariatric surgery have not yet been systematically analysed. Prospective studies in this field are necessary.

http://bit.ly/2QWISd9

The Need to Control for Confounding Factors on Analgesic Studies Involving Bariatric Patients

http://bit.ly/2VZh9Mp

Insulin-like growth factor 1 promotes cochlear synapse regeneration after excitotoxic trauma in vitro

Publication date: Available online 17 January 2019

Source: Hearing Research

Author(s): Kohei Yamahara, Nakarin Asaka, Tomoko Kita, Ippei Kishimoto, Mami Matsunaga, Norio Yamamoto, Koichi Omori, Takayuki Nakagawa

Abstract

In the context of acquired sensorineural hearing loss (SNHL), cochlear hair cells have long been thought to be among the most vulnerable elements in mammalian cochleae. However, recent studies have indicated that the synaptic connection between inner hair cells (IHC) and spiral ganglion neurons (SGN) can be an important target for the treatment of SNHL. Our previous studies in patients with sudden SNHL demonstrated delayed and gradual hearing recovery following topical application of insulin-like growth factor 1 (IGF-1), suggesting that not only protective but also regenerative mechanisms may account for hearing recovery after treatment with IGF-1. We then hypothesized that IGF-1 has the potential to drive the regeneration of IHC–SGN synapses. To test this hypothesis, we investigated the effects of IGF-1 on IHC–SGN synapses using cochlear explant cultures from postnatal day 2 mice that had been damaged by exposure to the excitatory amino acids N-methyl-d-aspartate and kainate. Cochlear explants that lost IHC–SGN synapses upon exposure to excitatory amino acids were cultured with exogenous IGF-1 for an additional 48 h. We observed increased numbers of IHC–SGN synapses after exogenous IGF-1 application. Pharmacological inhibition of the IGF-1 receptor attenuated the restoration of IHC–SGN synapses by exogenous IGF-1. These findings indicated that IGF-1 induces regeneration of IHC–SGN synapses in cochlear explant cultures from postnatal day 2 mice. Therefore, in a future study we will perform in vivo experiments using adult mice to ascertain the effects of IGF-1 on the regeneration of IHC–SGN synapses.

from #Audiology via ola Kala on Inoreader http://bit.ly/2DiJYvS

Progressive Hearing Damage after Exposure to Repeated Low-Intensity Blasts in Chinchillas

Publication date: Available online 17 January 2019

Source: Hearing Research

Author(s): Tao Chen, Kyle Smith, Shangyuan Jiang, Tianyu Zhang, Rong Z. Gan

Abstract

Hearing damage caused by blast waves is a frequent and common injury for Service members. However, most studies have focused on high-intensity blast exposures that are known to cause moderate to severe traumatic brain injury (TBI), and fewer studies have investigated the progressive hearing damage caused by low-intensity blast exposures (below mild TBI). In this paper, we report our recent study in chinchillas to investigate the auditory function changes over the time course after repetitive exposures to low-intensity blast. Two groups of chinchillas (N=7 each) were used in this study. Group 1 was for an acute study with 2 blasts and Group 2 for progressive study with 3 blasts on Day 1 and observed for 7 days. Animals in both groups were exposed to blast overpressures of 21-35 kPa (3-5 psi or 180-185 dB SPL) at which the eardrum was usually not ruptured. One ear was left open while another ear was protected with an earplug. Blast overpressures were monitored at the entrance of the ear canal (P0) and near the eardrum in the canal (P1). Auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), and middle latency responses (MLRs) were measured after each blast series in the acute group and on Days 1, 4, and 7 in the progressive group. Results show that hearing damage was induced in both ears after blast exposure on Day 1 and more damage was observed in open ears than plugged ears. Seven days after the three-blast series, the ABR threshold in open ears was still 7-20 dB higher on average than prior to the blasts. The MLR wave amplitude shifts were observed in both open and protected ears, which indicated central auditory damage. With the protection of an earplug, hearing thresholds had recovered to the pre-blast level by Day 7. Using this chinchilla blast model, acute and progressive hearing damages were quantified in both open and protected ears following repeated low-intensity blast exposures.

from #Audiology via ola Kala on Inoreader http://bit.ly/2U0l7Ts

Gap-induced inhibition of the post-auricular muscle response in humans and guinea pigs

Publication date: Available online 17 January 2019

Source: Hearing Research

Author(s): Caroline A. Wilson, Joel I. Berger, Jessica de Boer, Magdalena Sereda, Alan R. Palmer, Deborah A. Hall, Mark N. Wallace

Abstract

A common method for measuring changes in temporal processing sensitivity in both humans and animals makes use of GaP-induced Inhibition of the Acoustic Startle (GPIAS). It is also the basis of a common method for detecting tinnitus in rodents. However, the link to tinnitus has not been properly established because GPIAS has not yet been used to objectively demonstrate tinnitus in humans. In guinea pigs, the Preyer (ear flick) myogenic reflex is an established method for measuring the acoustic startle for the GPIAS test, while in humans, it is the eye-blink reflex. Yet, humans have a vestigial remnant of the Preyer reflex, which can be detected by measuring skin surface potentials associated with the Post-Auricular Muscle Response (PAMR). A similar electrical potential can be measured in guinea pigs and we aimed to show that the PAMR could be used to demonstrate GPIAS in both species.

In guinea pigs, we compare the GPIAS measured using the pinna movement of the Preyer reflex and the electrical potential of the PAMR to demonstrate that the two are at least equivalent. In humans, we establish for the first time that the PAMR provides a reliable way of measuring GPIAS that is a pure acoustic alternative to the multimodal eye-blink reflex. Further exploratory tests showed that while eye gaze position influenced the size of the PAMR response, it did not change the degree of GPIAS.

Our findings confirm that the PAMR is a sensitive method for measuring GPIAS and suggest that it may allow direct comparison of temporal processing between humans and animals and may provide a basis for an objective test of tinnitus.

from #Audiology via ola Kala on Inoreader http://bit.ly/2Dijjzz

Insulin-like growth factor 1 promotes cochlear synapse regeneration after excitotoxic trauma in vitro

Publication date: Available online 17 January 2019

Source: Hearing Research

Author(s): Kohei Yamahara, Nakarin Asaka, Tomoko Kita, Ippei Kishimoto, Mami Matsunaga, Norio Yamamoto, Koichi Omori, Takayuki Nakagawa

Abstract

In the context of acquired sensorineural hearing loss (SNHL), cochlear hair cells have long been thought to be among the most vulnerable elements in mammalian cochleae. However, recent studies have indicated that the synaptic connection between inner hair cells (IHC) and spiral ganglion neurons (SGN) can be an important target for the treatment of SNHL. Our previous studies in patients with sudden SNHL demonstrated delayed and gradual hearing recovery following topical application of insulin-like growth factor 1 (IGF-1), suggesting that not only protective but also regenerative mechanisms may account for hearing recovery after treatment with IGF-1. We then hypothesized that IGF-1 has the potential to drive the regeneration of IHC–SGN synapses. To test this hypothesis, we investigated the effects of IGF-1 on IHC–SGN synapses using cochlear explant cultures from postnatal day 2 mice that had been damaged by exposure to the excitatory amino acids N-methyl-d-aspartate and kainate. Cochlear explants that lost IHC–SGN synapses upon exposure to excitatory amino acids were cultured with exogenous IGF-1 for an additional 48 h. We observed increased numbers of IHC–SGN synapses after exogenous IGF-1 application. Pharmacological inhibition of the IGF-1 receptor attenuated the restoration of IHC–SGN synapses by exogenous IGF-1. These findings indicated that IGF-1 induces regeneration of IHC–SGN synapses in cochlear explant cultures from postnatal day 2 mice. Therefore, in a future study we will perform in vivo experiments using adult mice to ascertain the effects of IGF-1 on the regeneration of IHC–SGN synapses.

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Progressive Hearing Damage after Exposure to Repeated Low-Intensity Blasts in Chinchillas

Publication date: Available online 17 January 2019

Source: Hearing Research

Author(s): Tao Chen, Kyle Smith, Shangyuan Jiang, Tianyu Zhang, Rong Z. Gan

Abstract

Hearing damage caused by blast waves is a frequent and common injury for Service members. However, most studies have focused on high-intensity blast exposures that are known to cause moderate to severe traumatic brain injury (TBI), and fewer studies have investigated the progressive hearing damage caused by low-intensity blast exposures (below mild TBI). In this paper, we report our recent study in chinchillas to investigate the auditory function changes over the time course after repetitive exposures to low-intensity blast. Two groups of chinchillas (N=7 each) were used in this study. Group 1 was for an acute study with 2 blasts and Group 2 for progressive study with 3 blasts on Day 1 and observed for 7 days. Animals in both groups were exposed to blast overpressures of 21-35 kPa (3-5 psi or 180-185 dB SPL) at which the eardrum was usually not ruptured. One ear was left open while another ear was protected with an earplug. Blast overpressures were monitored at the entrance of the ear canal (P0) and near the eardrum in the canal (P1). Auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), and middle latency responses (MLRs) were measured after each blast series in the acute group and on Days 1, 4, and 7 in the progressive group. Results show that hearing damage was induced in both ears after blast exposure on Day 1 and more damage was observed in open ears than plugged ears. Seven days after the three-blast series, the ABR threshold in open ears was still 7-20 dB higher on average than prior to the blasts. The MLR wave amplitude shifts were observed in both open and protected ears, which indicated central auditory damage. With the protection of an earplug, hearing thresholds had recovered to the pre-blast level by Day 7. Using this chinchilla blast model, acute and progressive hearing damages were quantified in both open and protected ears following repeated low-intensity blast exposures.

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Gap-induced inhibition of the post-auricular muscle response in humans and guinea pigs

Publication date: Available online 17 January 2019

Source: Hearing Research

Author(s): Caroline A. Wilson, Joel I. Berger, Jessica de Boer, Magdalena Sereda, Alan R. Palmer, Deborah A. Hall, Mark N. Wallace

Abstract

A common method for measuring changes in temporal processing sensitivity in both humans and animals makes use of GaP-induced Inhibition of the Acoustic Startle (GPIAS). It is also the basis of a common method for detecting tinnitus in rodents. However, the link to tinnitus has not been properly established because GPIAS has not yet been used to objectively demonstrate tinnitus in humans. In guinea pigs, the Preyer (ear flick) myogenic reflex is an established method for measuring the acoustic startle for the GPIAS test, while in humans, it is the eye-blink reflex. Yet, humans have a vestigial remnant of the Preyer reflex, which can be detected by measuring skin surface potentials associated with the Post-Auricular Muscle Response (PAMR). A similar electrical potential can be measured in guinea pigs and we aimed to show that the PAMR could be used to demonstrate GPIAS in both species.

In guinea pigs, we compare the GPIAS measured using the pinna movement of the Preyer reflex and the electrical potential of the PAMR to demonstrate that the two are at least equivalent. In humans, we establish for the first time that the PAMR provides a reliable way of measuring GPIAS that is a pure acoustic alternative to the multimodal eye-blink reflex. Further exploratory tests showed that while eye gaze position influenced the size of the PAMR response, it did not change the degree of GPIAS.

Our findings confirm that the PAMR is a sensitive method for measuring GPIAS and suggest that it may allow direct comparison of temporal processing between humans and animals and may provide a basis for an objective test of tinnitus.

from #Audiology via ola Kala on Inoreader http://bit.ly/2Dijjzz
via IFTTT

Insulin-like growth factor 1 promotes cochlear synapse regeneration after excitotoxic trauma in vitro

Publication date: Available online 17 January 2019

Source: Hearing Research

Author(s): Kohei Yamahara, Nakarin Asaka, Tomoko Kita, Ippei Kishimoto, Mami Matsunaga, Norio Yamamoto, Koichi Omori, Takayuki Nakagawa

Abstract

In the context of acquired sensorineural hearing loss (SNHL), cochlear hair cells have long been thought to be among the most vulnerable elements in mammalian cochleae. However, recent studies have indicated that the synaptic connection between inner hair cells (IHC) and spiral ganglion neurons (SGN) can be an important target for the treatment of SNHL. Our previous studies in patients with sudden SNHL demonstrated delayed and gradual hearing recovery following topical application of insulin-like growth factor 1 (IGF-1), suggesting that not only protective but also regenerative mechanisms may account for hearing recovery after treatment with IGF-1. We then hypothesized that IGF-1 has the potential to drive the regeneration of IHC–SGN synapses. To test this hypothesis, we investigated the effects of IGF-1 on IHC–SGN synapses using cochlear explant cultures from postnatal day 2 mice that had been damaged by exposure to the excitatory amino acids N-methyl-d-aspartate and kainate. Cochlear explants that lost IHC–SGN synapses upon exposure to excitatory amino acids were cultured with exogenous IGF-1 for an additional 48 h. We observed increased numbers of IHC–SGN synapses after exogenous IGF-1 application. Pharmacological inhibition of the IGF-1 receptor attenuated the restoration of IHC–SGN synapses by exogenous IGF-1. These findings indicated that IGF-1 induces regeneration of IHC–SGN synapses in cochlear explant cultures from postnatal day 2 mice. Therefore, in a future study we will perform in vivo experiments using adult mice to ascertain the effects of IGF-1 on the regeneration of IHC–SGN synapses.

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via IFTTT

Progressive Hearing Damage after Exposure to Repeated Low-Intensity Blasts in Chinchillas

Publication date: Available online 17 January 2019

Source: Hearing Research

Author(s): Tao Chen, Kyle Smith, Shangyuan Jiang, Tianyu Zhang, Rong Z. Gan

Abstract

Hearing damage caused by blast waves is a frequent and common injury for Service members. However, most studies have focused on high-intensity blast exposures that are known to cause moderate to severe traumatic brain injury (TBI), and fewer studies have investigated the progressive hearing damage caused by low-intensity blast exposures (below mild TBI). In this paper, we report our recent study in chinchillas to investigate the auditory function changes over the time course after repetitive exposures to low-intensity blast. Two groups of chinchillas (N=7 each) were used in this study. Group 1 was for an acute study with 2 blasts and Group 2 for progressive study with 3 blasts on Day 1 and observed for 7 days. Animals in both groups were exposed to blast overpressures of 21-35 kPa (3-5 psi or 180-185 dB SPL) at which the eardrum was usually not ruptured. One ear was left open while another ear was protected with an earplug. Blast overpressures were monitored at the entrance of the ear canal (P0) and near the eardrum in the canal (P1). Auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), and middle latency responses (MLRs) were measured after each blast series in the acute group and on Days 1, 4, and 7 in the progressive group. Results show that hearing damage was induced in both ears after blast exposure on Day 1 and more damage was observed in open ears than plugged ears. Seven days after the three-blast series, the ABR threshold in open ears was still 7-20 dB higher on average than prior to the blasts. The MLR wave amplitude shifts were observed in both open and protected ears, which indicated central auditory damage. With the protection of an earplug, hearing thresholds had recovered to the pre-blast level by Day 7. Using this chinchilla blast model, acute and progressive hearing damages were quantified in both open and protected ears following repeated low-intensity blast exposures.

from #Audiology via ola Kala on Inoreader http://bit.ly/2U0l7Ts
via IFTTT