A 3-year-old child with alternate convergent squint and abnormal movements of eyes since 1 year

ONE MINUTE OPHTHALMOLOGY

Year : 2019  |  Volume : 67  |  Issue : 1  |  Page : 7

Hypopigmented fundus in a young male

Nawazish Fatma Shaikh, Vinod Kumar
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication

21-Dec-2018

Correspondence Address:
Dr. Vinod Kumar
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi - 110 029 
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/ijo.IJO_1834_18

 

How to cite this article: Shaikh NF, Kumar V. Hypopigmented fundus in a young male. Indian J Ophthalmol 2019;67:7

How to cite this URL: Shaikh NF, Kumar V. Hypopigmented fundus in a young male. Indian J Ophthalmol [serial online] 2019 [cited 2018 Dec 22];67:7. Available from: http://www.ijo.in/text.asp?2019/67/1/7/248137

Case

A 3-year-old boy presented with alternate convergent squint and abnormal movements of eyes since 1 year. Family and systemic history was unremarkable. The child had a best-corrected visual acuity of 20/100 in both eyes (OU). Ocular examination revealed pendular nystagmus and normal anterior segments in OU. Iris OU was brown-colored. Dilated fundus examination revealed a hypopigmented fundus with prominent choroidal vessels [Figure 1]a, [Figure 1]b. Macular pigments and foveal avascular zone (FAZ) were lacking in OU.

Figure 1: Dilated fundus examination revealed a hypopigmented fundus with prominent choroidal vessels (a and b). Macular pigments and foveal avascular zone (FAZ) were lacking in OU. Swept-source optical coherence tomography revealed an absent foveal contour and preservation of retinal layers in the foveal area (c and d) Click here to view

What is Your Next Step?

1. Refraction and optical coherence tomography (OCT)
2. Magnetic resonance imaging
3. Genetic analysis
4. Visual evoked potentials and electroretinogram

Findings

The child had a refractive error of + 3D in OU. Color vision was found to be normal for the child. Swept-source OCT revealed an absent foveal contour and preservation of retinal layers in the foveal area [Figure 1]c, [Figure 1]d. A diagnosis of ocular albinism and foveal hypoplasia was made, and the parents were explained about the prognosis. The child was prescribed glasses and was advised regular follow-up in addition to a strabismic evaluation.

Diagnosis

Ocular albinism with foveal hypoplasia

Correct Answer: A.

Discussion

Ocular albinism is an X-linked disorder in contrast to oculocutaneous albinism, which is inherited in a autosomal recessive manner.^[1],[2] Patients usually present with a variable decrease in visual acuity (visual acuity ranging from 20/60 to 20/400), nystagmus, strabismus, and photophobia. While oculocutaneous albinism is an easy diagnosis, ocular albinism may pose a diagnostic challenge as iris may not be hypopigmented.^[1],[2] The patients are frequently mistaken as having myopia as the fundus is lightly pigmented. Foveal hypoplasia is a frequent association and can be easily missed. Absent foveal reflex, FAZ, and macular pigments indicate foveal hypoplasia, which can be confirmed on OCT (preservation of retinal layers at fovea) or fundus fluorescein angiography (absent FAZ).

Ocular albinism is characterized by mutation in the GPR143 gene leading to dysfunctional melanosome ultimately resulting in macromelanosomes.^[1],[2] Melanin acts as an inducer and organizer of the formation of the fovea, optic nerves, optic tracts, and visual cortex. Absence or deficiency of melanin leads to ocular structure malformation and optic tract misrouting.

To conclude, high index of suspicion is required to diagnose ocular albinism as the fundus in these cases is easily confused with myopia.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 

References

1.	Federico JR, Krishnamurthy K. Albinism. [Updated 2018 Jul 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018.
2.	De Filippo E, Schiedel AC, Manga P. Interaction between G protein-coupled receptor 143 and tyrosinase: Implications for understanding ocular albinism type 1.J InvestDermatol2017;137:457-65.

The Scientific Journal of Al-Azhar Medical Faculty, Girls : Subarachnoid versus intravenous dexmedetomidine and fentanyl for minimizing stress response in laparoscopic cholecystectomy Mofeed Abdalla The Scientific Journal of Al-Azhar Medical Faculty, Girls 2018 2(3):137-143 Background The magnitude of stress response depends on several factors such as duration and intensity of surgical trauma, patient’s age, surgical method, anesthetic technique, blood loss, and postoperative pain. Aim of the work The aim of this work was to study the effect of intravenous versus intrathecal dexmedetomidine and fentanyl on stress response during laparoscopic cholecystectomy. Patients and methods Sixty patients fulfilling the inclusion criteria who were undergoing laparoscopic cholecystectomies were randomly assigned to receive either intravenous fentanyl and dexmedetomidine (group I) or intrathecal fentanyl and dexmedetomidine (group II). Mean arterial blood pressure and heart rate were recor

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Subarachnoid versus intravenous dexmedetomidine and fentanyl for minimizing stress response in laparoscopic cholecystectomy Mofeed Abdalla The Scientific Journal of Al-Azhar Medical Faculty, Girls 2018 2(3):137-143 Background The magnitude of stress response depends on several factors such as duration and intensity of surgical trauma, patient’s age, surgical method, anesthetic technique, blood loss, and postoperative pain. Aim of the work The aim of this work was to study the effect of intravenous versus intrathecal dexmedetomidine and fentanyl on stress response during laparoscopic cholecystectomy. Patients and methods Sixty patients fulfilling the inclusion criteria who were undergoing laparoscopic cholecystectomies were randomly assigned to receive either intravenous fentanyl and dexmedetomidine (group I) or intrathecal fentanyl and dexmedetomidine (group II). Mean arterial blood pressure and heart rate were recorded before induction of anesthesia (T0), 5 min after intubation (T1), 30 min after start of surgery (T2), at skin closure (T3), 6 h postoperatively (T4), and 24 h postoperatively (T5). The number of patients who required intraoperative intravenous fentanyl and total intraoperative fentanyl consumption (µg), and the number of patients who required intravenous morphine at the end of surgery were recorded. Visual analogue scale and total postoperative morphine consumption (mg) at the end of surgery (M0), and at 6, 12, 18, and 24 h (M1, M2, M3, and M4, respectively) were recorded. Blood interleukin-6, cortisol, and glucose were measured before anesthesia (F0) and after recovery (F1). Postoperative complications were recorded. Results Heart rate and mean arterial blood pressure were statistically lower in group II at T2 and T3. The number of patients requiring intraoperative intravenous fentanyl and total intraoperative fentanyl consumption (µg), and the number of patients requiring intravenous morphine at the end of surgery were statistically lower in group II. Visual analogue scale and postoperative morphine consumption (mg) were statistically lower in group II at M0 and M1. Blood cortisol and blood glucose level were statistically lower in group II at F1. There were no statistical differences as regards complications. Conclusion Apart from lowering heart rate and BP, intrathecal dexmedetomidine and fentanyl was superior to intravenous dexmedetomidine and fentanyl, wherein it lowered pain score and analgesic consumption with attenuation of stress response.

Comparison between subtenon block and extraconal block during cataract surgery Ahmed M Abd El-Galeel, Osama I.A Badr, Khaled G Mohamed The Scientific Journal of Al-Azhar Medical Faculty, Girls 2018 2(3):144-149 Background Most ophthalmic procedures are performed under local anesthesia, and cataract extraction is the most frequently performed surgery in elderly patients. The aim of this study is to compare the intraoperative hemodynamic variables, efficacy, and efficiency of extraconal block versus subtenon block with low concentration of local anesthetic during cataract surgery. Patients and methods This prospective, randomized, and single-blind study was done on 80 patients American Society of anesthesiologists status I–III undergoing cataract surgery, of which 40 patients underwent subtenon block (group S) and 40 patients underwent extraconal block (group E). Five minutes after the start of anesthetic monitoring care, 5-ml mixture of lidocaine 1% and bupivacaine 0.25% containing 100 IU hyalorunidase, in a mixture ratio of 1 : 1, was injected intraocular slowly. Patients were monitored for intraoperative hemodynamics, ocular movement during surgery, and intraoperative pain sensation as primary outcome, and onset of blockade, pain assessment within 30 min postoperatively, number of patients need rescue dose, surgeon discomfort, and postoperative complications as secondary outcomes. Results Mean arterial blood pressure and heart rate in group S were significantly lower than those in group E but within safety margin. No significant difference was found between the two groups regarding full range of eye movement, surgeon’s discomfort grade during cataract surgery, and also, intraoperative pain sensation. The onset of blockade was significantly faster in group S than group E. Although group S had better postoperative analgesic effect than group E, postoperative rescue dose was of insignificant value. Conclusion Subtenon block seems to be a better local anesthetic technique than extraconal for cataract surgery, as it is faster, has less surgeon discomfort grading, and better postoperative analgesia. However, on the contrary, both subtenon and extraconal blocks are equally effective in pain control during surgery and also have good ocular akinesia during operation.

Endometrial hyperplasia versus carcinoma: does phosphatase and tensin homolog immunohistochemical expression differentiate between them Marwa A El Kholy, Eman A El Kholy The Scientific Journal of Al-Azhar Medical Faculty, Girls 2018 2(3):150-155 Context Phosphatase and tensin homolog (PTEN) is a protein that acts as a tumor suppressor by dephosphorylating the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. Loss of PTEN function and mutation in PTEN gene have been implicated in the pathogenesis of endometrial carcinoma (EC). Objective The aim was to evaluate the immunohistochemical expression of PTEN in endometrial hyperplasia and EC and to evaluate the relationship between its expression and tumor grade in EC. Materials and methods Specimens included 16 cases of endometrial hyperplasia without atypia, six cases of atypical endometrial hyperplasia, and 18 EC specimens. Immunohistochemical staining for PTEN was performed using diaminobenzidine detection kit on formalin-fixed and paraffin-embedded tissue samples. Tumor tissue blocks and clinical data were collected from the files of the Pathology Department of Al-Zahraa University Hospital during the period 2010–2014. Results Immunohistochemistry showed that PTEN was positive for nuclei and cytoplasm of glandular endometrial cells. The PTEN expression was decreased significantly in atypical hyperplasia or EC compared with simple or complex hyperplasia (P0.041). In EC, we proved that PTEN expression is downregulated in high-grade tumors. Conclusion A positive PTEN expression correlates significantly with hyperplasia without atypia and well-differentiated tumors. The downregulation of PTEN indicates a more malignant phenotype.

Brain natriuretic peptide for prediction of mortality in patients with sepsis Amani K Mohamed, Nagwa Abd El-Ghaffar Mohamed, Nalgaa Abou-Elfattah Tawfik, Marwa Yahia Mohamed The Scientific Journal of Al-Azhar Medical Faculty, Girls 2018 2(3):156-162 Introduction Worldwide, sepsis is one of the leading causes of morbidity and mortality. Patients are at high risk for irreversible organ failure and a lethal course. About 60 000 individuals die from sepsis annually, and survivors have a reduced quality of life. In addition, sepsis places a considerable economic burden on the society. Early and comprehensive treatment improves outcome significantly. Brain natriuretic peptides (BNPs) are powerful predictors of death and major events in patients with stable coronary disease and pulmonary embolism. Several prospective studies have been carried out to investigate the potential role of BNPs in predicting mortality in septic patients in ICUs. The aim of this prospective study was to evaluate BNP for the prediction of mortality and myocardial dysfunction in severe sepsis and septic shock. Patients and methods This prospective study was carried out on 50 patients including group I, patients with sepsis, group (II), patients with severe sepsis, and group III, patients with septic shock. This study was carried out in the ICU of the Internal Medicine Department, Al-Zahraa University Hospital, in the period between January 2013 and March 2014 with written consents from our patients according to the ethical committee of the university. BNPs were determined by enzyme-linked immunosorbent assay. Results There was a highly statistical difference in the mean±SD of the BNP levels in group III (901.77±259.6) compared with group II (610.84±102.46), P value less than 0.01; also, there was a statistical difference in the BNP levels in group III (901.77±259.6) compared with group I (217.4±81.16), P value less than 0.01, whereas there was a statistically significant difference in group II (610.84±102.46) compared with group I (217.4±81.16), P value less than 0.05. In terms of the correlation between the BNP levels and other parameters of the patient groups, there was a highly positive significant correlation between BNP levels and the acute physiology and chronic health evaluation (APACHE II) score, the Sequential Organ Failure Assessment score, and white blood cells count. A significant positive correlation was found between BNP levels and prothrombin concentration (PC). There was a nonsignificant correlation between BNP and age, creatine phosphokinase, creatine kinase-MB, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, prothrombin time, international normalized ratio, and length of stay. Conclusion Our results suggested that an elevated BNP level may prove to be a powerful predictor of mortality in patients with sepsis. Future larger and more adequately powered prospective studies are warranted to clarify the prognostic value of BNPs in conjunction with other biomarkers.

Expression of TWIST1 and CD44 as diagnostic and prognostic biomarkers in patients with gastric cancer Marwa A El Kholy, Hala A El Sayed, Eman M Ahmed The Scientific Journal of Al-Azhar Medical Faculty, Girls 2018 2(3):163-170 Objective The aim of this study was to investigate the association of TWIST1 and CD44 in gastric cancer (GC) with clinical parameters and their relation to prognosis, which may be beneficial for targeted therapeutic strategies in the future. Materials and methods The material of this work consisted of 40 primary GC specimens from patients who underwent radical gastrectomy. Patients who received neoadjuvant chemotherapy or chemoradiotherapy, those who presented with other cancers at the same time, or the patients with incomplete clinical data were excluded from the study. Hematoxylin and eosin-stained sections from all cases were re-evaluated and further stained immunohistochemically using antibodies against TWIST1 and CD44. Results TWIST1 and CD44-positive expressions were significantly increased in GC cases of diffuse type (P=0.019 and 0.002, respectively). Moreover, there was a statistically significant correlation between both markers and tumor grade, stage, and lymphovascular invasion (P=0.027 and 0.010, P=0.002 and 0.012, and P=0.001 and 0.005, respectively). A statistically significant correlation was found between TWIST1 and CD44 expressions in GCs (P=0.000). Conclusion The presence of TWIST1-positive carcinoma cells and CD44-positive cancer stem-like cells in GC tissue can be used as a diagnostic tool for GC and regarded as a marker of poor prognosis in patients with GC, which may provide potential targets for GC therapy.

Homocysteinemia in relation to anemia in hypothyroid patients Samia Souka, Hanaa Kandil, Soheir Korraa, Aida A Abdel Hameed, Marwa Hassan The Scientific Journal of Al-Azhar Medical Faculty, Girls 2018 2(3):171-180 Background Anemia and hypothyroidism are both common diseases in the community. Homocysteine (HCY) levels are increased in patients with hypothyroidism and methylenetetrahydrofolate reductase (MTHFR) deficiency is the most common genetic cause of hyperhomocysteinemia. The aim of the present study was to evaluate the level of serum HCY in patients with hypothyroidism and to study the relation of associated anemia with the serum level of HCY and MTHFR gene in patients with hypothyroidism. Patients and methods The study was conducted on 60 adult women attending the Endocrinology Outpatient Clinic of Al-Zahraa Hospital between September 2014 and June 2015 for proper diagnosis and management. Individuals of the study were divided into two main groups: group I (GI) with 30 hypothyroid patients, where 13 of them were postsurgical cases, and group II (GII) with 30 euthyroid individuals as a control group. Diagnosis was based on thyroid-stimulating hormone level reference values. Patients in GI were further classified into two subgroups: mild hypothyroid (subgroup I) and overt hypothyroid (subgroup II). Patient and control groups also were classified into anemic and nonanemic subgroups according to hemoglobin levels. The selected hypothyroid patients were women under thyroid hormone replacement therapy. Blood sample was obtained for proper investigations. Complete blood count, routine blood chemistry, serum iron level, thyroid function tests, vitamin B12 level, serum homocysteine (HCY), and MTHFR were performed. We performed a pilot study on MTHFR gene polymorphism. The C677T MTHFR gene mutation was detected in three of 10 patients and in two of 10 controls. No evidence of TT MTHFR gene mutation was observed in both patient and control groups. IBM SPSS statistics (version 23.0, USA, 2015) was used for data analysis. Results revealed the presence of anemia according to hemoglobin level (<12 g/dl). In patients group (GI), 50% (15/30) as compared with 13.3% (4/30) in the control group (GII) had anemia. Serum iron level in patients group (GI) was deficient in 40% (11/30), whereas deficient in 16.7% (5/30) in control group (GII). Vitamin B12 deficiency was found to be 44% (11/25) in patients group (GI), whereas in the control group (GII) was 6.7% (2/30). Analysis by Wilcoxon’s rank sum test, homocysteine (HCY) serum level showed a highly significant increase among patients (GI) as compared with control (GII). Ranked Spearman’s correlation test for the patients (GI) and control (GII) showed a significant negative correlation between homocysteine (HCY) and MTHFR serum levels, whereas the correlation with red cell indices parameters was insignificant. Serum iron and B12 levels were significantly correlated in patient group (GI). Pearson χ2 tests were done between both patients and control groups for the presence of anemia, iron deficiency, and elevated serum homocysteine (HCY) level and all revealed statistically significant results. Conclusion There is no significant correlation between homocysteinemia and anemia. However, the strong association between anemia and hypothyroidism is attributed mainly owing to combined iron and vitamin B12 deficiencies. This might explain the decreased response to treatment among the selected hypothyroid patients.

Impact of direct-acting antiviral therapy in Egyptian patients with chronic hepatitis C and liver cirrhosis Mohammed H Elnadry, Sherif A Abdel-Aziz, Mohammed Ghareb, Ali A Ahamad, Nagah M Abu-Mohammed, Marwan M Tayel The Scientific Journal of Al-Azhar Medical Faculty, Girls 2018 2(3):181-188 Background and aims In Egypt, ∼14.7% of the population has hepatitis C infection and genotype 4 infection accounts for more than 90% of the hepatitis C virus infections. Available data with newer all-oral regimens in the treatment of genotype 4 infection suggest that sustained virological response (SVR) 12 rates in treatment-naïve cirrhotic and noncirrhotic patients are greater than 95%. The study aimed to evaluate the virological response 12 weeks after treatment (SVR12), change in the model for end-stage liver disease score, and adverse clinical events during the study period. Patients and methods This prospective study included 451 patients with chronic hepatitis C and liver cirrhosis over a 3-month period started at January 2017. And the study was ethically approved by the Medical Research Ethics Committee, Faculty of Medicine, Al-Azhar University. The enrolled patients were classified into three groups: group I included 162 patients with chronic hepatitis C and liver cirrhosis subjected to direct-acting antivirals (DAAs) therapy (100/162 compensated cirrhosis and 62/162 decompensated cirrhosis), group II included 234 patients known to have chronic hepatitis C without liver cirrhosis subjected to DAAs therapy, and group III included 55 patients with chronic hepatitis C and liver cirrhosis not subjected to DAAs therapy according to the national protocol of therapy (as a control group). Treatment was administered for 12 weeks that included variable regimens of DAAs according to the Egyptian Ministry of Health protocol. Results We included 451 patients with chronic hepatitis C infection and liver cirrhosis; 47.8% of the patients were male, 84.4% were treatment naive, and 54.9% had cirrhosis. Of the study participants, 150 patients in group I and 53 patients in group II received sofosbuvir+daclatasvir+ribavirin, 183 patients received daclatasvir+sofosbuvir (group II), seven patients in group II received sofosbuvir+ledipasvir, five patients received sofosbuvir+ledipasvir+ribavirin (in group I), and seven patients in group I and nine patients in group II received ombitasvir/paritaprevir/ritonavir+ribavirin. Twelve weeks after end of treatment (SVR12) were 91.3% and 96.5% observed in group I and group II, respectively irrespective of the regimen of therapy. Treated patients in group I had a mean negative change in model for end-stage liver disease (−0.722; SD, 2.603) representing an improvement in liver function, whereas untreated patients in group III showed a minimal mean positive change (0.00; SD, 2.92) representing a deterioration in liver function (P<0.001). Improvements were observed in the Child-score (Child–Pugh–Turcotte) in group I versus untreated patients in group III. Hepatic encephalopathy was evident in 6.1% of patients in group I after treatment versus 38.1% in untreated patients (group III), and ascites developed in 30.2% of patients after treatment (group I) versus 65.4% in untreated patients (group III). Conclusion Oral regimens of DAAs are effective in the treatment of hepatitis C virus infection even in patients with liver cirrhosis, leading to improvements in liver functions.

Studying the changes of ocular wavefront aberrations after neodymium : yttrium aluminum garnet laser capsulotomy Nermeen M Badawi The Scientific Journal of Al-Azhar Medical Faculty, Girls 2018 2(3):189-193 Aimof the study The aim of this study is to evaluate the changes of wavefront aberrations after performing neodymium : yttrium aluminum garnet (Nd : YAG) laser posterior capsulotomy for the management of posterior capsular opacifications. Patients and methods This study is a prospective study that was performed on 100 eyes of 87 patients with posterior capsule opacification following phacoemulsification, in the period from March 2017 to October 2017. A complete ophthalmic examination and optical wavefront imaging were performed to every patient. Patients underwent posterior capsulotomy using Nd : YAG laser with a follow-up period of 6 months. Results There were no significant changes in postoperative refraction at P value more than 0.05 still the best-corrected visual acuity showed a clinically significant at P value less than 0.05. The intraocular pressure was statistically significantly increased on the first postoperative day (P<0.05) but not in other postoperative visits. Regarding higher order aberrations there was a statistically significant improvement in total third-order aberrations (P<0.05), coma aberration (P<0.05), total fourth-order aberrations (P<0.05), spherical aberration (P<0.05), and total higher order aberrations (P<0.05) while quadrafoil and fifth-order aberrations showed no statistically significant changes. Conclusion Nd : YAG laser posterior capsulotomy causes a significantly decrease in wavefront aberrations in patients with posterior capsule opacification.

Bone mineral density in relation to polycystic ovary syndrome: an insight into irisin and insulin Olfat Fawzy, Nagwa A Elghaffar, Eman Mahmoud, Abeer Helmy The Scientific Journal of Al-Azhar Medical Faculty, Girls 2018 2(3):194-204 Background and aim Polycystic ovary syndrome (PCOS) is a complex metabolic and endocrine disorder. The influence of different metabolic and endocrine changes in women with PCOS and their relevance to bone status remains to be documented. Irisin is a newly identified adipo-myokine, which may play a role in the etiopathogenesis of PCOS as well as bone metabolism. The aim of the study was to assess bone mineral density (BMD) and serum irisin level in women with PCOS and to determine BMD relationship with irisin and other hormonal parameters. Patients and methods The study enrolled 80 women of reproductive age having PCOS and 15 age-matched and BMI-matched healthy women to serve as controls. A metabolic panel, reproductive hormones, and serum irisin level were measured. In addition, BMD of the spine and femur was also assessed using dual-energy X-ray absorptiometry. Results Serum irisin level, fasting insulin, and homeostatic model assessment of insulin resistance were significantly higher in the PCOS group compared with the control group. Receiver operating characteristic curve for serum irisin was done for the PCOS group and the control group and demonstrated that the cut-off value for serum irisin was 0.161 μg /dl. There was also a statistically significant difference between the PCOS group and the control group in BMD of spine and femur, being higher in the PCOS group. Logistic regression analysis has shown that serum irisin level, waist circumference, and fasting serum insulin were predictors for the z-score of spine in the PCOS group. Conclusion Serum irisin level may be considered as a novel biomarker for PCOS diagnosis. Circulating irisin in PCOS is strongly related to BMD. This suggests that irisin as an adipo-myokine may also be associated with bone metabolism.

Occult hepatitis B virus among patients with chronic hepatitis and hepatocellular carcinoma Khodeir A Naeima, Abd-El-Samae M Eman, Aly R Dina, El-Moatassem M Ola The Scientific Journal of Al-Azhar Medical Faculty, Girls 2018 2(3):205-211 Background Hepatitis B virus (HBV) infection is diagnosed when the circulating HBV surface antigen (HBsAg) is serologically detected. Occult HBV infection is defined as the infection state negative for HBsAg serology, but it has shown viral genome persistence in infected individuals. The aim of the study is to determine the prevalence of occult HBV among patients with chronic hepatitis negative to HBsAg in the presence or absence of hepatitis C virus (HCV) infection. Patients and methods This study was conducted on a total number of 55 patients with chronic hepatitis (liver cirrhosis in 44 cases, nonalcoholic fatty liver in six cases) and hepatocellular carcinoma in five cases. All studied cases were subjected to routine liver function tests, HBsAg, HBsAb, hepatitis c virus immunoglobulin G (HbcIgG), α-fetoprotein, HCV RNA, and HBV DNA detection. Result All cases were negative to HBsAg and HBsAb in the presence or absence of HCV infection. HBV DNA detection by real-time RT-PCR confirmed the positivity of HBV infection [occult hepatitis b infection (OBI)] in two (4.5%) out of 44 cases of cirrhotic liver and represented 3.6% of the total cases studied with a viral DNA of 116 and 159 copies/ml, respectively. One case of OBI had a high level of α-fetoprotein (392 Iu/ml) and the second case had high copies of HCV RNA 127 000 copies/ml, that is coinfection. HbcIgG was positive in 31.8% in cirrhotic patients (including one out of the two positive OBI). HCV RNA was negative in 100.0% of nonalcoholic fatty liver, positive in 39 (one was positive OBI) cases with cirrhosis with a median value of 45 000 copies and in four out of the five hepatocellular carcinoma cases with a median value of 1.85E+08. This is statistically significant (P=0.01). We come to the conclusion that occult HBV do exist in our community. The diagnosis of OBI should be based on high sensitivity of HBsAg and HBV DNA testing.

A method for the quantitative determination of glycerophospholipid regioisomers by UPLC-ESI-MS/MS

Abstract

Diacyl glycerophospholipids (GPs) belong to the most abundant lipid species in living organisms and consist of a glycerol backbone with fatty acyl groups in sn-1 and sn-2 and a polar head group in the sn-3 position. Regioisomeric mixed diacyl GPs have the same fatty acyl composition but differ in their allocation to sn-1 or sn-2 of the glycerol unit. In-depth analysis of regioisomeric mixed diacyl GP species composed of fatty acyl moieties that are similar in length and degree of saturation typically requires either chemical derivatization or sophisticated analytical instrumentation, since these types of regioisomers are not well resolved under standard ultra-performance liquid chromatography (UPLC) conditions. Here, we introduce a simple and fast method for diacyl GP regioisomer analysis employing UPLC tandem mass spectrometry (MS/MS). This GP regioisomer analysis is based both on minor chromatographic retention time shifts and on major differences in relative abundances of the two fatty acyl anion fragments observed in MS/MS. To monitor these differences with optimal precision, MS/MS spectra are recorded continuously over the UPLC elution profile of the lipid species of interest. Quantification of relative abundances of the regioisomers was performed by algorithms that we have developed for this purpose. The method was applied to commercially available mixed diacyl GP standards and to total lipid extracts of Escherichia coli (E. coli) and bovine liver. To validate our results, we determined regioisomeric ratios of phosphatidylcholine (PC) standards using phospholipase A₂-specific release of fatty acids from the sn-2 position of the glycerol backbone. Our results show that most analyzed mixed diacyl GPs of biological origin exhibit significantly higher regioisomeric purity than synthetic lipid standards. In summary, this method can be implemented in routine LC-MS/MS-based lipidomics workflows without the necessity for additional chemical additives, derivatizations, or instrumentation.

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Unsteadiness in gait, profuse sweating, exanthematous vesicular rash.Acute cerebellar ataxia due to varicella zoster virus

A rare neurological sequelae of chicken pox in an adult p. 268
Kandan Balamurugesan, Prem Davis, Rajangam Ponprabha, Malaimala Sarasveni
DOI:10.4103/2221-6189.248032  
Chicken pox is a disease of childhood caused by varicella zoster virus belonging to the α-herpesvirus-3 family. But the clinical presentation in adults is uncommon and is usually associated with complications. The complications are more commonly seen in immunocompromised individuals and in people who get infected at the later age group. Since the varicella zoster virus rarely causes cerebellar disease in adults, hence here we report a non-immunized, immune-competent adult patient presented to the emergency department with unsteadiness in gait, profuse sweating, exanthematous vesicular rash. We made a diagnosis of acute cerebellar ataxia due to varicella zoster virus and treated accordingly.
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Atypical case of severe preeclampsia complicated by generalized convulsions (eclampsia) and hemolysis, elevated liver enzymes, and low platelet count syndrome in an 18 weeks pregnant patient with chronic hypertension

Severe eclampsia and HELLP syndrome at 18 weeks of pregnancy in a patient with chronic hypertension p. 265
Tomasz Wojewoda, Edyta Unkiewicz, Ewa Wojewoda-Chmiel, Piotr Bijak, Michal Bogusiewicz
DOI:10.4103/2221-6189.248031  
Preeclampsia is a pregnancy specific disease characterized by hypertension and proteinuria, by definition, developing after 20 weeks of pregnancy. Here we present an atypical case of severe preeclampsia complicated by generalized convulsions (eclampsia) and hemolysis, elevated liver enzymes, and low platelet count syndrome in an 18 weeks pregnant patient with chronic hypertension. Occurrence of these complications was preceded by upper right quadrant abdominal pain and severe hypertension. In this case no evidence of autoimmunity disorders or molar pregnancy was found.
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Acute dengue hypokalemic paralysis complicated by hypomagensemia

 p. 262
Durgesh Pushkar, Bidyut Roy, Hirdesh Chawla, Tauhid Ahmad
DOI:10.4103/2221-6189.248030  
Endemic to over 100 countries dengue virus infection has now become the most rapidly spreading mosquito-borne disease in the world. Dengue symptoms range from minor flu-like symptoms to major complications like bleeding, shock, and rarely death due to organ failure. Atypical manifestations of neurological, cardiovascular, gastrointestinal origin are collectively grouped into the expanded dengue syndrome. Acute motor quadriparesis have been reported in several cases of dengue infection. We report a rare and non-fatal case of motor quadriparesis due to hypokalemia complicated by associated hypomagnesemia in a dengue positive patient.
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The changes of cognitive function after brain-blast injury

Changes of inflammatory factors, reactive oxygen species and cognitive function in mice after brain-blast injury p. 258
Ying Liu, Yun-En Liu, Chang-Ci Tong, Hong-Xu Jin
DOI:10.4103/2221-6189.248025  
Objective: To study the changes of cognitive function in mouse after brain-blast injury. Methods: Fourty healthy male C57BL/6 mice were randomly divided into model group and control group. After 24 h of injury, histopathological changesc and reactive oxygen species changes were observed under microscope; while changes of inflammatory cytokines content were determined by Western-blot. Four weeks later, Morris water maze method was used to detect the cognition impairment. Results: HE staining showed blast induced brain injury in C57BL/6 mice. Compared with normal control group, the expression of IL-1β,IL-4, IL-6 were significantly increased in brain tissue of model group whereas IL-10 was significantly decreased (P<0.05); ROS expression in the hippocampus of model group mice was significantly increased compared with that in the control group. Morris water maze showed cognition impairment in mice after brain-blast injury. Conclusions: Brain-blast injury causes cognition impairment in mice, which may be related to the occur of inflammatory change and oxidative stress in the early stage.
http://www.jadweb.org/currentissue.asp?sabs=y

The role of regulatory T cells (Tregs) at late stages of stroke

Effect of partial depletion of CD25+ T cells on neurological deficit and tissue damage in acute cerebral ischemia rat models p. 247
Ana L Rodriguez-Perea, Johanna Gutierrez-Vargas, Mauricio Rojas, Gloria P Cardona-Gomez, Paula A Velilla
DOI:10.4103/2221-6189.248029  
Objective: To evaluate the role of regulatory T cells (Tregs) at late stages of stroke. Methods: Anti-CD25 antibody (or PBS as a control) was injected to reduce the pool of Tregs in Wistar rats; then, ischemia was induced transiently by middle cerebral artery occlusion during 60 min and reperfusion was allowed for 7 d. Then, Treg frequency was analyzed in peripheral blood, spleen and lymph nodes. Neurological score (0-6) and infarct volume were also determined. Results: Nine days after injection, the CD4+CD25+ T cells were reduced by 70.4%, 44.8% and 57.9% in peripheral blood, spleen and lymph nodes, respectively compared to PBS-treated rats. In contrast, the reduction of CD4+FOXP3+ T cells was lower in the same compartments (38.6%, 12.5%, and 29.5%, respectively). The strongest reduction of CD25+CD4+ T cells was observed in those FOXP3-negative cells in blood, spleen and lymph nodes (77.8%, 52.8%, and 60.7%, respectively), most likely corresponding to activated T cells. Anti-CD25-treated transient middle cerebral artery occlusion rats had a lower neurological deficit and did not develop tissue damage compared with PBS-treated animals. Conclusions: These findings suggest that treatment with anti-CD25 in our model preferentially reduce the T cell population with an activated phenotype, rather than the Treg population, leading to neuroprotection by suppressing the pathogenic response of effector T cells.
http://www.jadweb.org/currentissue.asp?sabs=y

Intranasal ketamine as an analgesic agent for acute pain management in emergency department

: A literature review p. 241
Abdolghader Pakniyat, Morteza Qaribi, Dorin Rahnama Hezaveh, Ali Abdolrazaghnejad
DOI:10.4103/2221-6189.248028  
Ketamine is a well-known dissociative anesthetic agent, and has been used over 50 years. Intranasal pathway is a mucosal way for absorbing agents to directly affect in brain via olfactory sheets, bypassing first pass metabolism and the blood brain barrier. The current uses of intranasal ketamine as an analgesic agent for acute pain management in emergency department are discussed in this review article. Using "ketamine", "pain or analgesia", and "intranasal" as keywords, a search of google scholar, Pubmed, web of science, and Medline database from 1970 until 2017 was performed. Finally, from 1 204 papers extracted via primary search, 1 088 papers were omitted and finally 10 studies were considered for further assessment. There were four observational studies, one case series and report and 5 clinical trials. Ketamine was used for acute pain control due to musculoskeletal trauma, burns, and painful procedures. A total of 390 cases were included in these studies. The studies used ketamine with doses ranging 0.45-1.25 mg/kg via intranasal pathway. Intranasal ketamine provides relatively rapid, well tolerated, and clinically significant analgesia for emergency department patients. Considering the lack of adequate studies and undetermined intranasal dose, it is better to conduct further high quality investigation in both adults and pediatrics.
http://www.jadweb.org/currentissue.asp?sabs=y

Endogenous endophthalmitis secondary to melioidosis in paediatric patients

Endogenous endophthalmitis secondary to melioidosis in paediatric patients: Case series and review article p. 234
Wendy Ong Chin Feng, Wee Min Teh, Wan-Hazabbah Wan Hitam, Haslina Mohammad Ali
DOI:10.4103/2221-6189.248027  
Endogenous endophthalmitis is a devastating infection of the eye which can lead to permanent blindness. We report two rare cases of paediatric endogenous endophthalmitis secondary to melioidosis with contrasting visual outcomes. Both patients presented with acute painful visual loss with poor vision on presentation after exposure to open water sources (swimming at two separate locations with waterfalls). Both were diagnosed to have melioidosis endogenous endophthalmitis based on the ocular features clinically and via positive melioidosis serology. They otherwise did not exhibit any symptoms and signs suggestive of systemic melioidosis infection. Even though the two children demonstrated severe ocular involvement, ocular culture from vitreous and aqueous sampling taken from one of the patients did not yield any positive results. No ocular sampling was taken from the other patient. After standard antimicrobial treatment, the first patient responded well with good visual recovery without requiring any surgical intervention for the endophthalmitis. In contrast, our second patient ended up with poor visual outcome despite undergoing multiple intravitreal antibiotic injections and early pars plana vitrectomy. This is because he developed extensive retinal detachment due to the aggressive ocular infection. The diagnosis of endogenous endophthalmitis due to ocular melioidosis remains challenging and requires a high index of suspicion in areas endemic for the causative organism. Early empirical antibiotic treatment should be initiated in suspicious cases, even though the treatment outcomes may vary greatly
http://www.jadweb.org/currentissue.asp?sabs=y

Fast quantitative urinary proteomic profiling workflow for biomarker discovery in kidney cancer

Abstract

Background

Urine has evolved as a promising body fluids in clinical proteomics because it can be easily and noninvasively obtained and can reflect physiological and pathological status of the human body. Many efforts have been made to characterize more urinary proteins in recent years, but few have focused on the analysis throughput and detection reproducibility. Increasing the urine proteomic profiling throughput and reproducibility is urgently needed for discovering potential biomarker in large cohorts.

Methods

In this study, we developed a fast and robust workflow for streamlined urinary proteome analysis. The workflow integrate highly efficient sample preparation technique and urinary specific data-independent acquisition (DIA) approach. The performance of the workflow was systematically evaluated and the workflow was subsequently applied in a proof-of-concept urine proteome study of 21 kidney cancer (KC) patients and 22 healthy controls.

Results

With this workflow, the entire sample preparation process takes less than 3 h and allows multiplexing on standard centrifuges. Without pre-fractionation, our newly developed DIA method allows quantitative analysis of ~ 1000 proteins within 80 min of MS time (~ 15 samples/day). The quantitation accuracy of the whole workflow was excellent with median CV of 9.1%. The preliminary study on KC identified 125 significantly changed proteins.

Conclusions

The result suggested the feasibility of applying the high throughput workflow in extensive urinary proteome profiling and clinical relevant biomarker discovery.

http://bit.ly/2GJFQZY

Sex differences in mandibular repositioning device therapy effectiveness in patients with obstructive sleep apnea syndrome

Abstract

Purpose

Mandibular repositioning devices (MRDs) are an effective treatment option for obstructive sleep apnea syndrome (OSAS), particularly in patients who refuse or cannot tolerate continuous positive airway pressure (CPAP). However, sex differences in the response to therapy and predictors of response are not clearly defined. This analysis of data from the long-term prospective ORCADES trial compared MRD efficacy in men and women with OSAS.

Methods

The ORCADES study included patients with newly diagnosed mild-to-moderate or severe OSAS who refused or were non-compliant with CPAP. MRD therapy was titrated over 3–6 months. The primary endpoint was treatment success (≥ 50% decrease in apnea-hypopnea index (AHI)). Complete response was defined using a range of AHI cut-off values (< 5/h, < 10/h, < 15/h).

Results

Overall treatment success rates were 89% in women and 76% in men (p = 0.019); corresponding rates in those with severe OSAS (AHI > 30/h) were 100% and 68% (p = 0.0015). In women vs. men, overall complete response rates at AHI cut-off values of < 5/h, <10/h, and < 15/h were 49 vs. 34% (p = 0.0052), 78 vs. 62% (p = 0.016), and 92 vs. 76% (p = 0.0032). On multivariate analysis, significant predictors of MRD treatment success were overbite and baseline apnea index in men, and neck circumference and no previous CPAP therapy in women. There were sex differences in the occurrence of side effects. Temporomandibular joint pain was the most common reason for stopping MRD therapy.

Conclusions

MRD therapy was effective in women with OSA of any severity, with significantly higher response rates compared with men especially in severe OSAS.

Trial registration

www.clinicaltrials.gov (NCT01326143).

http://bit.ly/2EHr0RL

A quantitative model of relation between respiratory-related blood pressure fluctuations and the respiratory sinus arrhythmia

Abstract

In order to propose an interpretation of recent experimental findings concerning short-term variability of arterial blood pressure (ABP), heart rate variability (HRV), and their dependence on body posture, we develop a qualitative dynamical model of the short-term cardiovascular variability at respiratory frequency (HF). It shows the respiratory-related blood pressure fluctuations in relation to the respiratory sinus arrhythmia (RSA). Results of the model-based analysis show that the observed phenomena may be interpreted as buffering of the respiratory-related ABP fluctuations by heart rate (HR) fluctuations, i.e., the respiratory sinus arrhythmia. A paradoxical enhancement (PE) of the fluctuations of the ABP in supine position, that was found in experiment, is explained on the ground of the model, as an ineffectiveness of control caused by the prolonged phase shift between the the peak of modulation of the pulmonary flow and the onset of stimulation of the heart. Such phasic changes were indeed observed in some other experimental conditions. Up to now, no other theoretical or physiological explanation of the PE effect exists, whereas further experiments were not performed due to technical problems. Better understanding of the short-term dynamics of blood pressure may improve medical diagnosis in cardiology and diseases which alter the functional state of the autonomous nervous system.

Graphical Abstract

A simple mathematical model of cardiorespiratory dynamics. A novel class of mathematical models of blood pressure dynamics in humans allows to represent respiratory modulation of Arterial Blood Pressure. The model shows how the phase shift in neural control of the heart rate may produce Paradoxic Enhancement of respiratory Blood Pressure fluctuations. Observed in experiment. The model has many options for further development.

http://bit.ly/2EG8rxr

Can effusion-synovitis measured on ultrasound or MRI predict response to intra-articular steroid injection in hip osteoarthritis?

Abstract

Objectives

Intra-articular steroid injection (IASI) is an effective therapy for hip osteoarthritis (OA), but carries risks and provides significant pain relief to only two thirds of patients. We attempted to predict response to IASI in hip OA patients using baseline clinical, ultrasound, and MRI data.

Methods

Observational study of 97 subjects with symptomatic hip OA presenting for IASI. At baseline and 8 weeks we obtained hip MRI, grayscale and Doppler ultrasound, clinical range of motion (ROM), timed-up and go test (TUG) scores, and self-reported Western Ontario and McMaster Universities Osteoarthritis (WOMAC) pain, stiffness, and function scores. Bone-capsule distance (BCD) measurements of inflammation on hip ultrasound and MRI were measured at three locations: the proximal-most uncovered portion of the femoral head, the superficial-most (apex) portion of the femoral head, and the largest fluid pocket at the femoral neck.

Results

Ultrasound and MRI BCD correlated with each other significantly and strongly at the apex and neck. Power Doppler findings did not correlate significantly with any other imaging indices. Eight weeks post-injection, WOMAC pain, function, and stiffness scores significantly improved and TUG time improved nearly to the level of significance, but there were no significant changes in ultrasound, MRI, or Doppler indices. Baseline variables were not significantly different between responder and nonresponder WOMAC pain or TUG time cohorts.

Conclusion

Basic measures of inflammation on ultrasound and MRI are highly related to each other, but provide little insight into patient function and pain after IASI. Other mechanisms to explain improvement in patient status after IASI are likely at work.

http://bit.ly/2T2QUlW

Correction to: MRI assessment of the thigh musculature in dermatomyositis and healthy subjects using diffusion tensor imaging, intravoxel incoherent motion and dynamic DTI

The original version of this article, published on 04 June 2018, unfortunately contained a mistake.

http://bit.ly/2Aa3k4F

Highlights of the 22nd Annual Scientific Meeting of the Australasian Musculoskeletal Imaging Group [AMSIG] 2018, Gold Coast, Queensland, Australia

http://bit.ly/2EIeKAp

Intracardiac cement embolism during percutaneous vertebroplasty: incidence, risk factors and clinical management

Abstract

Objective

To evaluate the incidence and risk factors for ICE during a PV.

Materials and methods

Single-center retrospective analysis of 1512 consecutive patients who underwent 1854 PV procedures for osteoporotic (34 %), malignant (39.9 %) or other cause (26.1 %) of vertebral compression fractures (VCFs)/spine tumor lesions. Only thoracic or lumbar PVs were included. PVs were performed with polymethylmethacrylate (PMMA) low-viscosity bone cement under fluoroscopic guidance. Chest imaging (X-ray or CT) was performed the same day after PV in patients with high clinical suspicion of ICE. All post-procedural chest-imaging examinations were reviewed, and all ICEs were agreed upon in consensus by two radiologists.

Results

ICEs were detected in 72 patients (92 cement embolisms). In 86.1 % of the cases, concomitant pulmonary artery cement leakage was detected. Symptomatic ICEs were observed in six cases (8.3% of all ICEs; 0.32% of all PV procedures). No ICE led to death or permanent sequelae. Multiple levels treated during the same PV session were associated with a higher ICE rate [OR: 3.59, 95% CI: (1.98-6.51); p < 0.001]; the use of flat panel technology with a lower ICE occurrence [OR: 0.51, 95% CI: (0.32-0.83); p = 0.007].

Conclusion

Intracardiac cement embolism after PV has a low incidence (3.9 % in our study). Symptomatic complications related to ICE are rare (0.3%); none was responsible for clinical sequelae in our series.

Key Points

• The incidence of intracardiac cement embolism (ICE) during PVP is low (3.9%).

• Having a high number of treated vertebrae during the same session is a significant risk factor for ICE.

• Symptomatic intracardiac cement embolisms have a low incidence (8.3% of patients with ICE).

http://bit.ly/2CsiKCS

Incorporating musculoskeletal ultrasound into your radiology practice: patients, patience, and why your department cannot do without it

http://bit.ly/2T7I06V

A multicentre observational study of the effectiveness, safety and economic impact of nivolumab on non-small-cell lung cancer in real clinical practice

Abstract

Background Immunotherapy has become a standard treatment for lung cancer; however, the high cost makes it necessary to assess health outcomes. Objective The aim of this study was to evaluate the effectiveness, safety and economic cost of nivolumab in real-world clinical practice. Setting Fifteen regional and academic hospitals from Spain participated in this study. Methods This study was a retrospective, multicentre and observational study involving patients who experienced progression after first-line therapy for non-small-cell lung cancer and were treated with nivolumab between January 2016 and July 2017. Effectiveness and safety were evaluated by the oncologist, and the data from the electronic clinical records of the patients were collected by the research team. Economic cost was calculated using the cost of acquiring nivolumab for the public health system. Main outcome measures Effectiveness variables were overall survival (OS) and progression-free survival (PFS). The safety variable was the incidence of adverse events (AEs), and the cost per life-year gained (LYG) was the economic variable. Results A total of 221 patients were enrolled (83.7% men). The mean age was 64.5 years, and 84.6% of the patients had an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0–1. Squamous tumours accounted for 59.7% of the total, and 78.7% of the patients presented a time since platinum therapy (TPT) > 6 months. The mean nivolumab dose was 216 mg (SD 211), and the treatment duration was 7.0 months (95% CI 5.8–8.1). The median PFS was 5.3 months (95% CI 3.2–7.3), and OS was 9.7 months (95% CI 7.6–11.8). The median PFS and OS values were statistically significantly superior for patients with an ECOG score of 0–1 and for patients with a TPT > 6 months. The median OS was also statistically significantly superior for patients with non-squamous histology. Regarding safety, 71% of the patients presented AEs of any grade, and in 18.6%, the nivolumab treatment had to be delayed or discontinued. The cost of nivolumab per patient was €19,910.00 (SD 19,369), and the cost per LYG was €110,026.00 (€77,557.00–€231,171.00). Conclusions This study confirms that the efficacy and safety of nivolumab treatment in a real population are comparable to the results obtained in clinical trials. A greater clinical benefit of nivolumab therapy was observed in patients with an ECOG score of 0–1, a TPT > 6 months or non-squamous histology. Despite the benefit observed, the cost per LYG is above the threshold of efficiency established by public health institutes.

http://bit.ly/2GBSl9T

Hassles with medication management perceived by caregivers of adults who have intellectual or developmental disabilities

Abstract

Background Medication management is undertaken by caregivers of people who have intellectual or developmental disabilities. Objective The objectives were to measure the medication management hassles reported by caregivers of adults who have intellectual or developmental disabilities and to describe associations between characteristics of caregivers, medication regimens, and the person with intellectual or developmental disability and the scale score. Setting Web-based survey conducted in the United States. Method A newsletter announcement with a link to the survey was sent to members of a disability advocacy organization. Caregivers were age 18 years and older who manage medications for adults with intellectual or developmental disabilities. The survey questions were used to obtain characteristics of the caregiver, the medication regimen they managed, and the care-recipient. The study was approved by the Institutional Review Board of Michigan Medicine (HUM00091002). Main outcome measure The Family Caregiver Medication Administration Hassles Scale (caregiver scale). Results Forty-two caregivers responded, with 41 being female with a mean age of 56.7 years. The mean caregiver scale score was 28.9 (possible range 0–120). Highest scores (greatest hassles) were significantly associated with a greater level of support required by the care-recipient, stronger caregiver beliefs of the necessity of medication and concern about using medications, lack of previous caregiver health-care training, and being an employed caregiver rather than family member. Conclusion Medication management can contribute to caregiver stress. Pharmacists should ensure that caregivers are counseled about medication that they manage, be accessible for questions, and examine medication regimens to reduce polypharmacy and complexity of regimens.

http://bit.ly/2Rd7uT1

Exploring influences on pharmacists’ and students’ ethical reasoning in a changing practice landscape in Australia

Abstract

Background Practising pharmacists continuously develop their ethical reasoning skills, which evolve with practice experience and exposure to challenging scenarios. Considering the recent expansion of the roles of pharmacists and the paradigm shift in pharmacy practice, it is timely to explore community pharmacists' attitudes regarding the importance of ethics and their ethical reasoning. Objective To explore underlying factors influencing community pharmacists' and pharmacy students' ethical reasoning and attitudes towards pharmacy ethics, ethical reasoning processes and perceived current dilemmas. Setting Practising registered community pharmacists, pharmacists with provisional registration (interns) and final year pharmacy students in Australia. Method Two focus group discussions and two interviews were conducted with 16 Western Australian community pharmacists, interns and students. Participants were purposively selected for gender, background, practice setting, and practice experience. Main outcome measure Emerging themes embracing important influences on community pharmacists', interns' and students' ethical reasoning and perceived current ethical dilemmas and challenges. Results Two major themes embraced participants' ethical reasoning processes and conduct: (1) fundamental underpinning, from personal values and practice exposure, and (2) paradigm influenced, such as the changing healthcare landscape, expansion of roles, management of dilemmas, and competence. Increased frequency and complexity of ethical dilemmas related to role expansion. Rural pharmacists experienced unique ethical dilemmas in relation to practice isolation, privacy and confidentiality. Conclusion Changes in the community pharmacy practice environment has increasingly exposed pharmacists to more complex ethical dilemmas. Pharmacists practising in rural communities experience unique challenges. Structured and sound ethical reasoning skills are essential as pharmacists are faced with contemporary challenges.

http://bit.ly/2GzxEet

A curative-intent endoscopic surgery for postradiation nasopharyngeal necrosis in patients with nasopharyngeal carcinoma

Abstract

Background

Postradiation nasopharyngeal necrosis (PRNN) is a severe complication after radiotherapy in patients with nasopharyngeal carcinoma (NPC), which can severely affect the quality of life and threaten the patient's life. Only 13.4%–28.6% of patients can be cured by traditional repeated endoscopic debridement. Here, we introduced an innovative curative-intent endoscopic surgery for PRNN patients and evaluated its clinical efficacy.

Methods

Clinical data of 72 PRNN patients who underwent radical endoscopic necrectomy, followed by reconstruction using a posterior pedicle nasal septum and floor mucoperiosteum flap were analyzed to determine the efficacy of this surgery. The endpoints were complete re-epithelialization of the nasopharyngeal defect, relief of headache, and overall survival (OS).

Results

All surgeries were successfully performed without any severe postoperative complications or death. The median value of numeric rating scales of pain decreased from 8 before surgery to 0 after surgery (P < 0.001). Fifty-one patients (70.8%) achieved complete re-epithelialization of the nasopharyngeal defect. The number of cycles of radiotherapy (odds ratio [OR], 7.254; 95% confidence interval [CI] 1.035–50.821; P = 0.046), postoperative pathological result (OR, 34.087; 95% CI 3.168–366.746; P = 0.004), and survival status of flap (OR, 261.179; 95% CI 17.176–3971.599; P < 0.001) were independent risk factors of re-epithelialization of the nasopharyngeal defects. Postoperative pathological result (hazard ratio [HR], 5.018; 95% CI 1.970–12.782; P = 0.001) was an independent prognostic factor for OS. The 2-year OS rate of the entire cohort was 77.9%.

Conclusion

Curative-intent endoscopic necrectomy followed by construction using the posterior pedicle nasal septum and floor mucoperiosteum flap is a novel, safe, and effective treatment of PRNN in patients with NPC.

http://bit.ly/2PSf8xq

Infliximab for treatment-refractory transverse myelitis following immune therapy and radiation

Abstract

Background

Neurologic toxicities with immune therapy are rare, but can cause devastating and often permanent injury when they occur. Although there is increasing interest in the potential synergism between immune therapy and radiation, it is possible that such combinations may lead to a greater number or increased severity of immune-related adverse events. We present here a case of extensive and progressive transverse myelitis following combined therapy, which did not improve until treatment with infliximab. This case highlights the unmet need for treatment of adverse events that are refractory to consensus recommendations, and may ultimately require further study and incorporation into future published guidelines.

Case presentation

We report a case of a 68-year-old with metastatic melanoma, who developed transverse myelitis in the setting of immune checkpoint blockade and spinal irradiation for vertebral metastases. Despite management according to published consensus guidelines: cessation of immune therapy, high-dose steroids, and plasmapheresis, he continued to deteriorate neurologically, and imaging revealed a progressive and ascending transverse myelitis. The patient was then treated with infliximab, and demonstrated dramatic imaging and modest clinical improvement following the first treatment cycle.

Conclusions

This is the first report describing the successful use of infliximab in immune therapy and radiation-related transverse myelitis that was not responding to recommended therapy. Evaluation of additional treatment options such as infliximab for high-grade immune-related neurologic toxicities is warranted, and may be needed earlier in the disease process to prevent significant morbidity. The adverse effects of immune therapy when used in combination with radiation also require further investigation.

http://bit.ly/2QIGMlM

Immune-checkpoint inhibitor plus chemotherapy versus conventional chemotherapy for first-line treatment in advanced non-small cell lung carcinoma: a systematic review and meta-analysis

Abstract

Background

Immune-checkpoint inhibitors plus chemotherapy are emerging as effective first-line treatment in advanced non-small-cell lung carcinoma (NSCLC), but little is known about the magnitude of benefits and potential clinical predictors.

Methods

We performed a meta-analysis of randomized trials that compared PD-1/PD-L1 inhibitor plus chemotherapy with chemotherapy in first line of treatment for advanced NSCLC. The outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and treatment-related adverse events (AEs). A fixed-effect or random-effects model was adopted depending on between-study heterogeneity.

Results

Six trials involving 3144 patients were included. PD-1/PD-L1 inhibitor plus chemotherapy was significantly associated with improvement of PFS (hazards ratio [HR], 0.62; 95% CI 0.57–0.67; P < .001), OS (HR, 0.68; 95% CI 0.53–0.87; P = .002) and ORR (relative ratio [RR], 1.56; 95% CI 1.29–1.89; P < .001), irrespective of PD-L1 expression level. The significant predictor(s) for treatment benefit with combination therapy versus chemotherapy alone were PD-L1 expression level for PFS (P < .001); types of checkpoint inhibitor for ORR (P < .001); histology (P = .025), age (P = .038), gender (P < .001), and types of checkpoint inhibitor (P < .001) for OS. In safety analyses, PD-1/PD-L1 inhibitor plus chemotherapy had significantly higher incidence of adverse events (AEs) of grade 3 or higher (RR, 1.14; P = .007), AEs leading to treatment discontinuation (RR, 1.29; P = .022), serious AEs (RR 1.70; P = .006), immune mediated AEs of any grade (RR, 2.37; P < .001), and immune mediated AEs of grade 3 or higher (RR, 3.71; P < .001).

Conclusions

PD-1/PD-L1 inhibitor plus chemotherapy, compared with chemotherapy, is associated with significantly improved PFS, ORR, and OS in first-line therapy in NSCLC, at the expense of increased treatment-related AEs.

http://bit.ly/2ByLYhO