Πέμπτη 14 Ιανουαρίου 2021

Aggressive Treatment Including Endonasal Surgical Sequestrectomy with Vascularized Nasoseptal Flap Can Improve Outcomes of Skull Base Osteoradionecrosis

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J Neurol Surg B Skull Base
DOI: 10.1055/s-0040-1722669

Objective Skull base osteoradionecrosis (SB-ORN) is a serious, potentially lethal complication of radiation therapy. We aimed to review the clinical characteristics and outcomes of SB-ORN according to the extent of treatment. Design Retrospective analysis design was used for this study. Setting The study was conducted in two tertiary care hospitals. Participants Patients included who had been clinically diagnosed with SB-ORN from January 2006 to 2017. Main Outcome Measures Clinical characteristics, including demographics, predisposing factors, presenting symptoms, radiological findings, treatment modalities, and treatment outcomes, were reviewed. Treatment was classified into conservative and aggressive types. Aggressive treatment included radical surgical removal of soft tissue and bony sequestrum with the placement of vascularized tissue. Treatment outcome was analyzed in terms of clinical control, survival, and carotid artery blow out. Results Fifteen patients (11 males and 4 females) were identified during the study period. Eight patients were managed conservatively, whereas seven patients were managed with aggressive treatment. The 2-year survival was 75% in the aggressive treatment group and 15% in the conservative group (log-rank, p = 0.049). The estimated 2-year blow out free rate was 46.7% for the conservative group and 100% for the aggressive group (log-rank, p = 0.100). Conclusion In patients with SB-ORN, aggressive management, including surgical removal of sequestrum and coverage with a pedicled flap, is associated with increased survival.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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Cognitive Pathways to Belief in Karma and Belief in God

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Abstract

Supernatural beliefs are ubiquitous around the world, and mounting evidence indicates that these beliefs partly rely on intuitive, cross‐culturally recurrent cognitive processes. Specifically, past research has focused on humans' intuitive tendency to perceive minds as part of the cognitive foundations of belief in a personified God—an agentic, morally concerned supernatural entity. However, much less is known about belief in karma—another culturally widespread but ostensibly non‐agentic supernatural entity reflecting ethical causation across reincarnations. In two studies and four high‐powered samples, including mostly Christian Canadians and mostly Hindu Indians (Study 1, N = 2,006) and mostly Christian Americans and Singaporean Buddhists (Study 2, N = 1,752), we provide the first systematic empirical investigation of the cognitive intuitions underlying various forms of belief in karma. We used path analyses to (a) replicate tests of t he previously documented cognitive predictors of belief in God, (b) test whether this same network of variables predicts belief in karma, and (c) examine the relative contributions of cognitive and cultural variables to both sets of beliefs. We found that cognitive tendencies toward intuitive thinking, mentalizing, dualism, and teleological thinking predicted a variety of beliefs about karma—including morally laden, non‐agentic, and agentic conceptualizations—above and beyond the variability explained by cultural learning about karma across cultures. These results provide further evidence for an independent role for both culture and cognition in supporting diverse types of supernatural beliefs in distinct cultural contexts.

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Automation of Quantifying Axonal Loss in Patients with Peripheral Neuropathies through Deep Learning Derived Muscle Fat Fraction

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Background

Axonal loss denervates muscle, leading to an increase of fat accumulation in the muscle. Therefore, fat fraction (FF) in whole limb muscle using MRI has emerged as a monitoring biomarker for axonal loss in patients with peripheral neuropathies. In this study, we are testing whether deep learning‐based model can automate quantification of the FF in individual muscles. While individual muscle is smaller with irregular shape, manually segmented muscle MRI images have been accumulated in this lab; and make the deep learning feasible.

Purpose

To automate segmentation on muscle MRI images through deep learning for quantifying individual muscle FF in patients with peripheral neuropathies.

Study Type

Retrospective.

Subjects

24 patients and 19 healthy controls.

Field Strength/Sequences

3T; Interleaved 3D GRE.

Assessment

A 3D U‐Net model was implemented in segmenting muscle MRI images. This was enabled by leveraging a large set of manually segmented muscle MRI images. B1 + and B1 maps were used to correct image inhomogeneity. Accuracy of the automation was evaluated using Pixel Accuracy (PA), Dice Coefficient (DC) in binary masks; and Bland‐Altman and Pearson correlation by comparing FF values between manual and automated methods.

Statistical Tests

PA and DC were reported with their median value and standard deviation. Two methods were compared using the ± 95% confidence intervals (CI) of Bland‐Altman analysis and the Pearson's coefficient (r 2).

Results

DC values were from 0.83 ± 0.17 to 0.98 ± 0.02 in thigh and from 0.63 ± 0.18 to 0.96 ± 0.02 in calf muscles. For FF values, the overall ± 95% CI and r 2 were [0.49, –0.56] and 0.989 in thigh and [0.84, –0.71] and 0.971 in the calf.

Data Conclusion

Automated results well agreed with the manual results in quantifying FF for individual muscles. This method mitigates the formidable time consumption and intense labor in manual segmentations; and enables the use of individual muscle FF as outcome measures in upcoming longitudinal studies.

Level of Evidence

3

Technical Efficacy Stage

1

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Delivery of Anti‐microRNA‐712 to Inflamed Endothelial Cells Using Poly(β‐amino ester) Nanoparticles Conjugated with VCAM‐1 Targeting Peptide

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Delivery of Anti‐microRNA‐712 to Inflamed Endothelial Cells Using Poly(β‐amino ester) Nanoparticles Conjugated with VCAM‐1 Targeting Peptide

In this study, novel poly(β‐amino ester) (pBAE) nanoparticles (NPs) conjugated with VHPK peptides that target vascular cell adhesion molecule 1 are developed and used to deliver RNA interference drugs to inflamed endothelial cells (ECs). Specifically, these VHPK‐conjugated pBAE NPs successfully deliver anti‐microRNA‐712 to inflamed ECs both in vitro and in vivo and reduce expression of the pro‐atherogenic microRNA‐712.


Abstract

Endothelial cells (ECs) are an important target for therapy in a wide range of diseases, most notably atherosclerosis. Developing efficient nanoparticle (NP) systems that deliver RNA interference (RNAi) drugs specifically to dysfunctional ECs in vivo to modulate their gene expression remains a challenge. To date, several lipid‐based NPs are developed and shown to deliver RNAi to ECs, but few of them are optimized to specifically target dysfunctional endothelium. Here, a novel, targeted poly(β‐amino ester) (pBAE) NP is demonstrated. This pBAE NP is conjugated with VHPK peptides that target vascular cell adhesion molecule 1 protein, overexpressed on inflamed EC membranes. To test this approach, the novel NPs are used to deliver anti‐microRNA‐712 (anti‐miR‐712) specifically to inflamed ECs both in vitro and in vivo, reducing the high expression of pro‐atherogenic miR‐712. A single administration of anti‐miR‐712 using the VHPK‐conjugated‐pBAE NPs in mic e significantly reduce miR‐712 expression, while preventing the loss of its target gene, tissue inhibitor of metalloproteinase 3 (TIMP3) in inflamed endothelium. miR‐712 and TIMP3 expression are unchanged in non‐inflamed endothelium. This novel, targeted‐delivery platform may be used to deliver RNA therapeutics specifically to dysfunctional endothelium for the treatment of vascular disease.

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A Colon‐Targeted Oral Probiotics Delivery System Using an Enzyme‐Triggered Fuse‐Like Microcapsule

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A Colon‐Targeted Oral Probiotics Delivery System Using an Enzyme‐Triggered Fuse‐Like Microcapsule

In the present work, an enzyme‐triggered fuse‐like microcapsule is constructed for the colon‐targeted oral probiotics delivery. By overcoming a series of physiological barriers, the microcapsule is detonated with the help of trypsin, which results in that the encapsulated probiotics can be released, then adhere, and colonize in the colon.


Abstract

Probiotics are closely related to human health. However, it is hard to find an appropriate disintegration mode for encapsulation to balance the survival, release, and adhesion of probiotics simultaneously during the current colon‐targeted oral delivery, which leads to limited colonization. In this study, an enzyme‐triggered fuse‐like microcapsule is constructed using alginate and protamine via the electrostatic droplet combined with the layer by layer self‐assembly. The multilayer microcapsule can protect the probiotics in the stomach and disintegrate layer by layer under the catalysis of trypsin in the intestine. The formulation with two protamine layers showed the best protection for Escherichia coli MG1655 (EM) during the oral delivery; as well the minimal release at the gastric pH value but a burst release after 1 h at the intestinal pH value. In particular, the adhesion strength of EM is improved with the increase of the layer number. In vivo experiments demons trate that the EM enters into the stationary phase within 12 h in the colon. Moreover, the blood biochemistry and histological analysis demonstrates the safety of the microcapsule formulation. It can be concluded that this microcapsule can help the probiotics survive during the delivery, then release and colonize in the colon.

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Cascade Catalytic Nanoplatform Based on “Butterfly Effect” for Enhanced Immunotherapy

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Cascade Catalytic Nanoplatform Based on

The GOD‐catalyzed glucose oxidation not only realizes tumor starvation therapy, but also provides H2O2 for IONP mediated Fenton reaction. In addition, the iron ions released from mesoporous IONP catalyzes Artemisinin for reactive oxygen species (ROS) generation. Therefore, the cascade catalytic nanoplatform generates ROS based on "the butterfly effect", enhancing immunotherapy.


Abstract

The unique tumor microenvironment (TME) characteristics such as immunosuppression impeded traditional cancer treatments. In contrast, developing cascade catalytic nanoplatforms by fully making use of substances in TME for cancer therapy may deserve full credit. Herein, a cascade catalytic nanoplatform based on glucose oxidase (GOD) modified mesoporous iron oxide nanoparticles (IONP) loaded with Artemisinin (ART) is developed, which is designed as IONP‐GOD@ART. GOD can catalyze the oxidization of glucose into gluconic acid and H2O2, which not only realizes tumor starvation therapy, but also provides H2O2 for IONP mediated Fenton reaction. Simultaneously, mesoporous IONP releases Fe2+ and Fe3+ ions in acidic TME. On the one hand, iron ions undergo Fenton reaction to generate hydroxyl radicals for chemodynamic therapy. On the other hand, the endoperoxide bridge in ART is broken in presence of Fe2+ and furt her generates reactive oxygen species (ROS) to achieve therapeutic purpose. In this sense, IONP‐GOD@ART manipulates TME characteristics and leads to "butterfly effect", which brings out a large amount of ROS for eliciting immunogenic cell death, inducing M1‐TAMs polarization, and further reprogramming immunosuppressive TME for enhanced immunotherapy. By this delicate design, the cascade catalytic nanoplatform of IONP‐GOD@ART realizes potent cancer immunotherapy for tumor regression and metastasis prevention.

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Multifocal glioblastoma—two case reports and literature review

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Abstract

Background

Multifocal glioblastoma is a rare type of glioblastoma with worse prognosis. In this article, we aimed to report two cases of classical multifocal glioblastoma.

Case presentation

In case 1, a 47-year-old male presented with dizziness, and once had a sudden loss of consciousness accompanied by convulsion of limbs. Contrast-enhanced MRI showed multiple lesions with heterogeneously ring-enhanced characters in the left hemisphere, diagnosed as multifocal glioblastoma. He underwent a craniotomy of all lesions, concurrent radiotherapy and chemotherapy as well as additional chemotherapy of temozolomide. After 2 cycles, repeat MRI showed that the new lesions already occurred and progressed. Eventually, he abandoned the chemotherapy after the 2 cycles and died 1 year later. In case 2, a 71-year-old male presented with a history of headache, left limb weakness, and numbness. Discontinuous convulsion of limbs once occurred. Contrast-enhanced MRI showed multiple lesions located in the right hemisphere, diagnosed as multifocal glioblastoma. He underwent a right frontoparietal craniotomy of the main lesion. Hemorrhage of the residual tumor an d pulmonary artery embolism occurred synchronously. Eventually, his family decided not to pursue any further treatment and opted for hospice care and he passed away within 11 days of surgery.

Conclusions

We reported two cases of typical multifocal glioblastoma. Valid diagnosis is crucial; then, resection of multiple lesions and canonical radio-chemotherapy probably bring survival benefits.

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Rheumatology-led pregnancy clinic: men perspective

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Abstract

The birth of reproductive rheumatology as a subject of interest in rheumatology has led to improvement of clinical care for patients living with autoimmune rheumatic diseases and paved the way towards setting a specialized pregnancy service within the standard rheumatology practice. In contrast to women, where there has been wealth of literature regarding pregnancy, lactation, and birth outcomes, there is not as much focusing on male sexual health and outcomes among inflammatory arthritis patients. Challenges such as decrease ability to conceive, impaired fertility, erectile dysfunction, and other sexual problems have been raised by male patients living with autoimmune rheumatic diseases. This broad scope gives the reproductive health concept in men another expansion with views to include sexual health problems screening among men attending the standard outpatient rheumatology clinics. This article adds to the paucity of real-life experience and aims at discussin g the sexual health from the men perspective and provides a practical approach towards screening, and assessment of men living with autoimmune diseases in standard day to day practice.

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Body mass index as an independent prognostic factor in glioblastoma

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Abstract

Purpose

Glioblastoma prognosis remains dismal despite gross total removal (GTR) followed by chemoradiotherapy. Other known prognostic factors include functional status, age and IDH mutation status. However, to improve patient outcome, a search for other features with impact on survival is needed. We aimed to analyse the impact of body mass index (BMI) on overall survival (OS) and progression-free survival (PFS) of surgically resected primary glioblastoma and evaluate if BMI constitutes an independent prognostic factor.

Methods

We analysed all adult glioblastoma patients who underwent surgery and chemoradiotherapy between 2011 and 2017 at our institution. Overall survival was the study—primary endpoint, and progression-free survival—the secondary endpoint. We assayed age, gender, histology, extent of resection, IDH, functional and smoking status, cardiovascular risk factors, BMI, OS and PFS. Univariate analysis was conducted followed by multivariate analysis to establish independent prognostic factors. In accordance with the World Health Organization (WHO) BMI stratification, survival curves were obtained for normal-weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2) and obese (≥ 30 kg/m2) patient subgroups in addition to the non-obese (18.5–29.9 kg/m2) population.

Results

193 patients were evaluated, with a median follow-up time of 17.3 months. Median OS was 21.3 months in obese patients vs 16.2 months in the non-obese (p = 0.017) and 16 months in the normal weight (p = 0.007). Higher median OS was also observed in patients under 60 and those in which GTR was obtained. Median PFS in obese individuals was 9 months in comparison to 6 months in the normal-weight subgroup (p = 0.04) and 7 months in the non-obese (p = 0.050). Multivariate analysis identified age < 60 (p = 0.044), GTR (p = 0.004) and BMI ≥ 30 (p = 0.009) as independent prognostic factors for increased overall survival.

Conclusion

Higher BMI was associated with longer OS and PFS. Prospective studies are needed to validate these findings.

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On recent meta-analyses of exposure to glyphosate and risk of non-Hodgkin’s lymphoma in humans

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Abstract

Purpose

A recent meta-analysis of five case–control studies and one cohort study reported that exposure to glyphosate was associated with increased risk of non-Hodgkin's lymphoma (NHL). The meta-analysis was based on estimates of risk from the included studies at the highest reported exposure level obtained from analyses with the longest lag period. The extent to which the summary estimate depends upon the exposure definitions and assumed latency period is uncertain.

Methods

We carried out sensitivity analyses to determine how the definition of exposure and the choice of latency period affect the summary estimate from meta-analyses of the 6 studies included in the recent meta-analysis. We also conducted a meta-analysis of ever-exposure to glyphosate incorporating the most updated results from the case–control studies.

Results

The summary estimates of risk varied considerably depending on both the assumptions about exposure level and latency. Using the highest reported exposure levels, evidence of an association between glyphosate and NHL was strongest when estimates from analyses in the cohort study with a 20-year lag [RR = 1.41 (95% CI 1.13–1.76)] and a 15-year lag [RR = 1.25 (95% CI 1.01–1.25)] were included. In our meta-analysis of ever-exposure with no lag period, the summary relative risk with updated estimates was 1.05 (95% CI 0.87–1.28).

Conclusion

The results of meta-analyses of glyphosate exposure and NHL risk depend on assumptions made about both exposure level and latency period. Our results for ever-exposure are consistent with those of two recent meta-analyses conducted using somewhat different study inclusion criteria.

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Integrating lipidomics and genomics: emerging tools to understand cardiovascular diseases

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Abstract

Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity worldwide leading to 31% of all global deaths. Early prediction and prevention could greatly reduce the enormous socio-economic burden posed by CVDs. Plasma lipids have been at the center stage of the prediction and prevention strategies for CVDs that have mostly relied on traditional lipids (total cholesterol, total triglycerides, HDL-C and LDL-C). The tremendous advancement in the field of lipidomics in last two decades has facilitated the research efforts to unravel the metabolic dysregulation in CVDs and their genetic determinants, enabling the understanding of pathophysiological mechanisms and identification of predictive biomarkers, beyond traditional lipids. This review presents an overview of the application of lipidomics in epidemiological and genetic studies and their contributions to the current understanding of the field. We review findings of these studies and discuss exa mples that demonstrates the potential of lipidomics in revealing new biology not captured by traditional lipids and lipoprotein measurements. The promising findings from these studies have raised new opportunities in the fields of personalized and predictive medicine for CVDs. The review further discusses prospects of integrating emerging genomics tools with the high-dimensional lipidome to move forward from the statistical associations towards biological understanding, therapeutic target development and risk prediction. We believe that integrating genomics with lipidome holds a great potential but further advancements in statistical and computational tools are needed to handle the high-dimensional and correlated lipidome.

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