neuroGPT-X: toward a clinic-ready large language model.

OBJECTIVE: The objective was to assess the performance of a context-enriched large language model (LLM) compared with international neurosurgical experts on questions related to the management of vestibular schwannoma. Furthermore, another objective was to develop a chat-based platform incorporating in-text citations, references, and memory to enable accurate, relevant, and reliable information in real time. METHODS: The analysis involved 1) creating a data set through web scraping, 2) developing a chat-based platform called neuroGPT-X, 3) enlisting 8 expert neurosurgeons across international centers to independently create questions (n = 1) and to answer (n = 4) and evaluate responses (n = 3) while blinded, and 4) analyzing the evaluation results on the management of vestibular schwannoma. In the blinded phase, all answers were assessed for accuracy, coherence, relevance, thoroughness, speed, and overall rating. All experts were unblinded and provided their thoughts on the utility and limitations of the tool. In the unblinded phase, all neurosurgeons provided answers to a Likert scale survey and long-answer questions regarding the clinical utility, likelihood of use, and limitations of the tool. The tool was then evaluated on the basis of a set of 103 consensus statements on vestibular schwannoma care from the 8th Quadrennial International Conference on Vestibular Schwannoma. RESULTS: Responses from the naive and context-enriched Generative Pretrained Transformer (GPT) models were consistently rated not significantly different in terms of accuracy, coherence, relevance, thoroughness, and overall performance, and they were often rated significantly higher than expert responses. Both the naive and content-enriched GPT models provided faster responses to the standardized question set than expert neurosurgeon respondents (p < 0.01). The context-enriched GPT model agreed with 98 of the 103 (95%) consensus statements. Of interest, all expert surgeons expressed concerns about the reliability of GPT in accurately addressing the nuances and controversies surrounding the management of vestibular schwannoma. Furthermore, the authors developed neuroGPT-X, a chat-based platform designed to provide point-of-care clinical support and mitigate the limitations of human memory. neuroGPT-X incorporates features such as in-text citations and references to enable accurate, relevant, and reliable information in real time. CONCLUSIONS: The present study, with its subspecialist-level performance in generating written responses to complex neurosurgical problems for which evidence-based consensus for management is lacking, suggests that context-enriched LLMs show promise as a point-of-care medical resource. The authors anticipate that this work will be a springboard for expansion into more medical specialties, incorporating evidence-based clinical information and developing expert-level dialogue surrounding LLMs in healthcare.

Assessing the research landscape and clinical utility of large language models: a scoping review.

IMPORTANCE: Large language models (LLMs) like OpenAI's ChatGPT are powerful generative systems that rapidly synthesize natural language responses. Research on LLMs has revealed their potential and pitfalls, especially in clinical settings. However, the evolving landscape of LLM research in medicine has left several gaps regarding their evaluation, application, and evidence base. OBJECTIVE: This scoping review aims to (1) summarize current research evidence on the accuracy and efficacy of LLMs in medical applications, (2) discuss the ethical, legal, logistical, and socioeconomic implications of LLM use in clinical settings, (3) explore barriers and facilitators to LLM implementation in healthcare, (4) propose a standardized evaluation framework for assessing LLMs' clinical utility, and (5) identify evidence gaps and propose future research directions for LLMs in clinical applications. EVIDENCE REVIEW: We screened 4,036 records from MEDLINE, EMBASE, CINAHL, medRxiv, bioRxiv, and arXiv from January 2023 (inception of the search) to June 26, 2023 for English-language papers and analyzed findings from 55 worldwide studies. Quality of evidence was reported based on the Oxford Centre for Evidence-based Medicine recommendations. FINDINGS: Our results demonstrate that LLMs show promise in compiling patient notes, assisting patients in navigating the healthcare system, and to some extent, supporting clinical decision-making when combined with human oversight. However, their utilization is limited by biases in training data that may harm patients, the generation of inaccurate but convincing information, and ethical, legal, socioeconomic, and privacy concerns. We also identified a lack of standardized methods for evaluating LLMs' effectiveness and feasibility. CONCLUSIONS AND RELEVANCE: This review thus highlights potential future directions and questions to address these limitations and to further explore LLMs' potential in enhancing healthcare delivery.

Automated Paper Screening for Clinical Reviews Using Large Language Models: Data Analysis Study.

BACKGROUND: The systematic review of clinical research papers is a labor-intensive and time-consuming process that often involves the screening of thousands of titles and abstracts. The accuracy and efficiency of this process are critical for the quality of the review and subsequent health care decisions. Traditional methods rely heavily on human reviewers, often requiring a significant investment of time and resources. OBJECTIVE: This study aims to assess the performance of the OpenAI generative pretrained transformer (GPT) and GPT-4 application programming interfaces (APIs) in accurately and efficiently identifying relevant titles and abstracts from real-world clinical review data sets and comparing their performance against ground truth labeling by 2 independent human reviewers. METHODS: We introduce a novel workflow using the Chat GPT and GPT-4 APIs for screening titles and abstracts in clinical reviews. A Python script was created to make calls to the API with the screening criteria in natural language and a corpus of title and abstract data sets filtered by a minimum of 2 human reviewers. We compared the performance of our model against human-reviewed papers across 6 review papers, screening over 24,000 titles and abstracts. RESULTS: Our results show an accuracy of 0.91, a macro F1-score of 0.60, a sensitivity of excluded papers of 0.91, and a sensitivity of included papers of 0.76. The interrater variability between 2 independent human screeners was κ=0.46, and the prevalence and bias-adjusted κ between our proposed methods and the consensus-based human decisions was κ=0.96. On a randomly selected subset of papers, the GPT models demonstrated the ability to provide reasoning for their decisions and corrected their initial decisions upon being asked to explain their reasoning for incorrect classifications. CONCLUSIONS: Large language models have the potential to streamline the clinical review process, save valuable time and effort for researchers, and contribute to the overall quality of clinical reviews. By prioritizing the workflow and acting as an aid rather than a replacement for researchers and reviewers, models such as GPT-4 can enhance efficiency and lead to more accurate and reliable conclusions in medical research.

Outcomes of Laparoscopic Sleeve Gastrectomy (LSG) vs One-Anastomosis Gastric Bypass (OAGB) in Patients with Super-Super Obesity (BMI ≥ 60 kg/m2).

INTRODUCTION: The data comparing laparoscopic sleeve gastrectomy (LSG) and one-anastomosis gastric bypass (OAGB) in patients with BMI ≥ 60 kg/m2 is scarce. METHODS: Prospectively collected data of patients with BMI ≥ 60 kg/m2 undergoing LSG or OAGB from January 2008 until June 2022 was analyzed retrospectively. Weight loss outcomes, impact on comorbidities, and complications were compared in both groups. RESULTS: Fifty-six patients underwent LSG and 13 patients underwent OAGB. The median age and BMI were 37 (34-44) years and 63 (61.3-64.6) kg/m2 respectively. Both the groups had similar baseline demographic parameters. The percentage excess BMI loss (%EBMIL) was statistically similar in LSG and OAGB groups at 1 year (46.2% vs 46.1%), 3 years (52.9% vs 56.7%), and 5 years (51.1% vs 62.3%). The percentage excess BMI regain was lower (although statistically similar) following OAGB at 3 years (5.3% vs 0.1%) and 5 years (12.9% vs 4.4%). OAGB was found to correlate positively with weight loss and negatively with weight regain (p > 0.05). There was one 30-day mortality due to postoperative lower respiratory infection in the LSG group. CONCLUSION: OAGB has a trend towards better weight loss outcomes as compared to LSG in patients with a BMI ≥ 60 kg/m2 with lesser complication rates and might be a preferred option. LSG also has acceptable weight loss and should be considered a standalone procedure if OAGB is not feasible technically.

Development and validation of a 21-gene prognostic signature in neuroblastoma.

Survival outcomes for patients with neuroblastoma vary markedly and reliable prognostic markers and risk stratification tools are lacking. We sought to identify and validate a transcriptomic signature capable of predicting risk of mortality in patients with neuroblastoma. The TARGET NBL dataset (n = 243) was used to develop the model and two independent cohorts, E-MTAB-179 (n = 478) and GSE85047 (n = 240) were used as validation sets. EFS was the primary outcome and OS was the secondary outcome of interest for all analysis. We identified a 21-gene signature capable of stratifying neuroblastoma patients into high and low risk groups in the E-MTAB-179 (HR 5.87 [3.83-9.01], p < 0.0001, 5 year AUC 0.827) and GSE85047 (HR 3.74 [2.36-5.92], p < 0.0001, 5 year AUC 0.815) validation cohorts. Moreover, the signature remained independent of known clinicopathological variables, and remained prognostic within clinically important subgroups. Further, the signature was effectively incorporated into a risk model with clinicopathological variables to improve prognostic performance across validation cohorts (Pooled Validation HR 6.93 [4.89-9.83], p < 0.0001, 5 year AUC 0.839). Similar prognostic utility was also demonstrated with OS. The identified signature is a robust independent predictor of EFS and OS outcomes in neuroblastoma patients and can be combined with clinically utilized clinicopathological variables to improve prognostic performance.

Mechanisms and clinical implications in renal carcinoma resistance: narrative review of immune checkpoint inhibitors.

Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of renal cell carcinoma. The prognosis for patients with ccRCC has improved over recent years with the use of combination therapies with an anti-programmed death-1 (PD-1) backbone. This has enhanced the quality of life and life expectancy of patients with this disease. Unfortunately, not all patients benefit; eventually, most patients will develop resistance to therapy and progress. Recent molecular, biochemical, and immunological research has extensively researched anti-angiogenic and immune-based treatment resistance mechanisms. This analysis offers an overview of the principles underpinning the resistance pathways related to immune checkpoint inhibitors (ICIs). Additionally, novel approaches to overcome resistance that may be considered for the trial context are discussed.

Treatment-Free Survival After Nivolumab vs Pembrolizumab vs Nivolumab-Ipilimumab for Advanced Melanoma.

Importance: Treatment-free survival (TFS) represents an alternative time-to-event end point, accurately characterizing time spent free of systemic therapy, providing a more patient-centric view of immune checkpoint inhibitor (ICI) therapy regimens. There remains a lack of studies evaluating TFS outcomes among patients with advanced melanoma who are receiving immunotherapy, especially outside of the clinical trial setting. Objective: To evaluate TFS outcomes for patients with advanced melanoma receiving first-line ICI therapy outside of a clinical trial setting. Design, Setting, and Participants: This multicenter cohort study of patients with advanced melanoma receiving first-line ICI therapy between August 1, 2013, and May 31, 2020, was conducted in Alberta, Canada. Data analysis was performed in August 2022. Exposures: Patients received standard-of-care, first-line ICI therapy treatment regimens including single-agent nivolumab, single-agent pembrolizumab, or ipilimumab-nivolumab. Main Outcomes and Measures: Treatment-free survival was defined as the difference in the 36-month restricted mean survival time between 2 conventional survival end points: (1) time from treatment initiation to ICI cessation, death, or censoring at last follow-up and (2) time from treatment initiation to subsequent systemic anticancer therapy, death, or censoring at last follow-up. Results: A total of 316 patients with advanced melanoma receiving first-line nivolumab (n = 51; median age, 66 years [IQR, 56-78 years]; 31 men [60.8%]), pembrolizumab (n = 158; median age, 69 years [IQR, 60-78 years]; 112 men [70.9%]), or combination nivolumab-ipilimumab (n = 107; median age, 53 years [IQR, 42-60 years]; 72 men [67.3%]) were included. Treatment groups were similar with regard to sex, primary tumor location, and presence of metastasis, although patients receiving combination nivolumab-ipilimumab had a lower Eastern Cooperative Oncology Group status, were younger, and were more likely to be BRAF V600E positive than those receiving anti-programmed cell death protein 1 (anti-PD-1) monotherapy. The restricted mean TFS was longer for nivolumab-ipilimumab (12.4 months [95% CI, 8.8-16.0 months]) compared with nivolumab (8.9 months [95% CI, 4.4-13.5 months]) and pembrolizumab (11.1 months [95% CI, 8.5-13.8 months]). During the 36-month follow-up interval, patients treated with nivolumab-ipilimumab spent 34.4% of their time (12.4 of 36 months) not receiving systemic anticancer treatments compared with 30.8% (11.1 of 36 months) and 24.7% (8.9 of 36 months) of the time for the pembrolizumab and nivolumab treatment groups, respectively. Conclusions and Relevance: This cohort study of patients with advanced melanoma receiving first-line ICI therapy suggests that TFS represents a patient-centric, informative end point. Patients treated with combination nivolumab-ipilimumab spent more time alive and free from systemic anticancer therapy than those treated with anti-PD-1 monotherapy alone.

Development and Validation of a Prognostic Risk Model for Patients with Advanced Melanoma Treated with Immune Checkpoint Inhibitors.

BACKGROUND: Risk stratification tools for patients with advanced melanoma (AM) treated with immune checkpoint inhibitors (ICI) are lacking. We identified a new prognostic model associated with overall survival (OS). PATIENTS AND METHODS: A total of 318 treatment naïve patients with AM receiving ICI were collected from a multi-centre retrospective cohort study. LASSO Cox regression identified independent prognostic factors associated with OS. Model validation was carried out on 500 iterations of bootstrapped samples. Harrel's C-index was calculated and internally validated to outline the model's discriminatory performance. External validation was carried out in 142 advanced melanoma patients receiving ICI in later lines. RESULTS: High white blood cell count (WBC), high lactate dehydrogenase (LDH), low albumin, Eastern Cooperative Oncology Group (ECOG) performance status ≥1, and the presence of liver metastases were included in the model. Patients were parsed into 3 risk groups: favorable (0-1 factors) OS of 52.9 months, intermediate (2-3 factors) OS 13.0 months, and poor (≥4 factors) OS 2.7 months. The C-index of the model from the discovery cohort was 0.69. External validation in later-lines (N = 142) of therapy demonstrated a c-index of 0.65. CONCLUSIONS: Liver metastases, low albumin, high LDH, high WBC, and ECOG≥1 can be combined into a prognostic model for AM patients treated with ICI.

Trends in health care spending on kidney cancer in the United States, 1996-2016.

BACKGROUND: Paradigm shifts in kidney cancer management have led to higher health care spending. Here, total and per capita health care spending and primary drivers of change in health expenditures for kidney cancer in the United States between 1996 and 2016 are estimated. METHODS: Public databases developed by the Institute for Health Metrics and Evaluation for the Disease Expenditure Project were used. The prevalence of kidney cancer was estimated from the Global Burden of Disease Study. Changes in health care spending on kidney cancer were assessed by joinpoint regression and expressed as annual percent changes (APCs). RESULTS: In 2016, total health care spending on kidney cancer was $3.42 billion (95% CI, $2.91 billion to $3.89 billion) compared with $1.18 billion (95% CI, $1.07 billion to $1.31 billion) in 1996. Per capita spending had two inflection points in 2005 and 2008, close to the approval years of targeted therapies, which corresponded to APCs of +2.9% (95% CI, +2.3% to +3.6%; p < .001) per year, 1996-2005; +9.2% (95% CI, +3.4% to +15.2%; p = .004) per year, 2005-2008; and +3.1% (95% CI, +2.2% to +3.9%; p < .001) per year, 2008-2016. Inpatient care was the largest contributor to health expenditures, which accounted for $1.56 billion (95% CI, $1.19 billion to $1.95 billion) in 2016. Price and intensity of care was the primary driver of increased health expenditures, whereas service utilization was the primary driver of reduced health expenditures. CONCLUSIONS: Prevalence-adjusted health care spending on kidney cancer continues to rise in the United States, which is primarily attributable to inpatient care and driven by the price and intensity of care over time.

Banded Sleeve Gastrectomy vs Non-banded Sleeve Gastrectomy: a Systematic review and Meta-analysis.

Banded sleeve gastrectomy (BSG) was developed to restrict progressive dilation of the gastric sleeve, which remains a commonly implicated reason for weight regain following SG. The present study attempted to perform a systematic review and meta-analysis comparing the two procedures. Literature search was performed across PubMed and Google Scholar, using the keywords "Banded Sleeve Gastrectomy", "Sleeve gastrectomy", "Banded", "BSG" and "LSG". It yielded 4267 articles, six of which have been included in this review. Better weight loss outcomes at 3 and 5 years are noted following BSG, with a margin of 6.39% and 9.97% in %TWL at respective time points. No difference in impact on co-morbidities was noted. A revision rate of 7.1% was seen after BSG, with increased regurgitation as the most common indication.

Gastrointestinal Quality of Life in Morbidly Obese Patients Undergoing One Anastomosis Gastric Bypass (OAGB): Derivation of a "Mini GIQLI" Score.

BACKGROUND: One anastomosis gastric bypass (OAGB) is now one of the mainstream bariatric surgical procedures with proven safety and efficacy. However, data on the gastrointestinal quality of life following OAGB is lacking. METHODS: This is a retrospective analysis of a prospectively collected database, performed at a single tertiary care teaching hospital from January 2016 until March 2021. All patients undertook the Gastrointestinal Quality of Life Index (GIQLI) questionnaire. GIQLI was correlated with various parameters. Principal component analysis (PCA) was used to assess the importance of each question in the questionnaire and devise a "Mini GIQLI score". RESULTS: A total of 60 patients were included. The %TWL at 3 and 5 years was 26.2 ± 11.9%, 31.7 ± 11 respectively. The mean weight regain was 5.6 ± 8.5 kg. The mean GIQLI score was 125 ± 13.1. The mean scores for questions pertaining to gastrointestinal, social, psychological, and physical domains were 3.49, 3.7, 3.45, and 3.27 respectively. Scree plot of principal component analysis showed that a new score ("Mini GIQLI") combining only 5 questions had good correlation with the overall GIQOL score (r = 0.842). The five questions related to anxiety, fatigue, feeling unwell, loss of endurance, and feeling unfit. CONCLUSIONS: Patients report a good score on GIQLI assessment following OAGB. The Mini GIQLI score is a quicker tool with good correlation to the full-length GIQLI score.

Expression of risk genes linked to vitamin D receptor super-enhancer regions and their association with phenotype severity in multiple sclerosis.

Multiple sclerosis (MS) is a chronic debilitating neurological condition with a wide range of phenotype variability. A complex interplay of genetic and environmental factors contributes to disease onset and progression in MS patients. Vitamin D deficiency is a known susceptibility factor for MS, however the underlying mechanism of vitamin D-gene interactions in MS etiology is still poorly understood. Vitamin D receptor super-enhancers (VSEs) are enriched in MS risk variants and may modulate these environment-gene interactions. mRNA expression in total of 64 patients with contrasting MS severity was quantified in select genes. First, RNA-seq was performed on a discovery cohort (10 mild, 10 severe MS phenotype) and ten genes regulated by VSEs that have been linked to MS risk were analyzed. Four candidates showed a significant positive association (GRINA, PLEC, PARP10, and LRG1) in the discovery cohort and were then quantified using digital droplet PCR (ddPCR) in a validation cohort (33 mild, 11 severe MS phenotype). A significant differential expression persisted in the validation cohort for three of the VSE-MS genes: GRINA (p = 0.0138), LRG1 (p = 0.0157), and PLEC (p = 0.0391). In summary, genes regulated by VSE regions that contain known MS risk variants were shown to have differential expression based on disease severity (p<0.05). The findings implicate a role for vitamin D super-enhancers in modulating disease activity. In addition, expression levels may have some utility as prognostic biomarkers in the future.

Phylogenetic and Ancestral Sequence Reconstruction of SARS-CoV-2 Reveals Latent Capacity to Bind Human ACE2 Receptor.

SARS-CoV-2 is a unique event, having emerged suddenly as a highly infectious viral pathogen for human populations. Previous phylogenetic analyses show its closest known evolutionary relative to be a virus detected in bats (RaTG13), with a common assumption that SARS-CoV-2 evolved from a zoonotic ancestor via recent genetic changes (likely in the Spike protein receptor-binding domain or RBD) that enabled it to infect humans. We used detailed phylogenetic analysis, ancestral sequence reconstruction, and in situ molecular dynamics simulations to examine the Spike-RBD's functional evolution, finding that the common ancestral virus with RaTG13, dating to no later than 2013, possessed high binding affinity to the human ACE2 receptor. This suggests that SARS-CoV-2 likely possessed a latent capacity to bind to human cellular targets (though this may not have been sufficient for successful infection) and emphasizes the importance of expanding efforts to catalog and monitor viruses circulating in both human and non-human populations.

Correlation between pre-operative endoscopic findings with reflux symptom score for gastro-oesophageal reflux disease in bariatric patients.

INTRODUCTION: There is a strong association between gastro-oesophageal reflux disease and morbid obesity. METHODS: Two hundred and eleven morbidly obese patients operated between September 2007 and June 2017 were retrospectively reviewed. All patients underwent pre-operative upper gastrointestinal endoscopy and assessment by reflux symptomatic score questionnaire. RESULTS: Of the total 211 patients, 156 (73.94%) were females; mean body mass index of the cohort was 46.23 ± 3.1 kg/m2. There was no evidence of Barrett's oesophagus or malignancy on pre-operative endoscopy. 63.04% of the patients (n = 133) in the study cohort had normal endoscopy. Pre-operative evaluation by reflux symptom score (RSS) questionnaire revealed no evidence of gastro-oesophageal reflux disease in 61.13% of patients (n = 129). The total number of patients with symptoms was 82 (38.86%). They were further divided into two categories based on severity of symptoms, namely, mild + moderate 60 (73.17%) and severe + very severe 22 (26.83%). From the cohort of symptomatic patients, the sub-cohort of 60 mild + moderate symptomatic patients had equal number of patients with normal 30 (50%) and abnormal endoscopy 30 (50%). In the sub-cohort of patients with severe + very severe symptoms (n = 22; 26.83%), endoscopy was abnormal in 6 (27.7%) patients. Whereas, out of 129 (61.13%) asymptomatic patients, one-third (n = 42) had abnormal endoscopy. The weighted kappa score was used between pre-operative endoscopic findings and RSS was statistically not significant (k - 0.0986). CONCLUSION: Pre-operative endoscopy is a must in all bariatric patients as significant percentage of asymptomatic patients can have abnormal endoscopy and vice versa.

Impact of bariatric surgery on type 2 diabetes in morbidly obese patients and its correlation with pre-operative prediction scores.

BACKGROUND: Bariatric surgery, besides causing significant weight reduction, leads to improvement in type 2 diabetes mellitus (T2DM). However, there is a scarcity of data on the prediction of diabetes resolution in non-Western population. OBJECTIVE: To evaluate the impact of bariatric surgery on T2DM and to assess the accuracy of pre-operative scoring systems in predicting remission. STUDY SETTING: A tertiary care academic centre, India. METHODOLOGY: We used a retrospective cohort of all diabetic patients (n = 244) who underwent bariatric surgery at our centre in the past 10 years. The cohort was followed up for diabetes remission, and pre-operative scoring systems were analysed against the observed results. RESULTS: Of 244 patients, we were able to contact 156 patients. The median period of follow-up was 38 months. The mean body mass index (BMI) of the study group decreased from 45.4 to 33.4 kg/m2 (%excess BMI loss = 61.2%). The number of patients dependent on oral anti-diabetic pharmacotherapy and on insulin decreased from 133 (85.3%) to 40 (25.6%) and from 31 (19.9%) to 7 (4.5%), respectively. Remission was analysed for 96 patients, who submitted complete biochemical investigations. The median follow-up period for this sub-cohort was 36 months. 38 (39.6%) patients were in complete remission, 15 (15.6%) patients in partial remission and 34 (38.5%) patients showed an improved glycaemic control. The three pre-operative scores, Advanced-DiaRem, DiaRem and ABCD, showed predictive accuracies of 81.1%, 75.6% and 77.8%, respectively. CONCLUSIONS: Besides leading to excess BMI loss of 61.2%, bariatric surgery also resulted in diabetes remission in 55.2% of the patients. Amongst various pre-operative scores, Advanced-DiaRem has the highest predictive accuracy for T2DM remission.

Infant and young child feeding practices among mothers of children aged 6 months -2 years in a rural area of Haryana: A qualitative study.

BACKGROUND: India, a low-middle income and a developing country is combating with a triple burden of malnutrition with a very cost-effective measure, infant and young child feeding (IYCF) practices. But there are a lot of challenges in its implementation which need to be catered. The objective of the present qualitative study was to assess IYCF practices among mothers of children aged 6 months to 2 years in a rural area of Haryana. METHOD: Qualitative study was carried out among mothers of children 6 months-2 years in villages of Ballabgarh block of Haryana using focussed group discussion (FGD) and in-depth interview methods. All recordings of FGDs and IDIs were transcribed into verbatim and codes were generated. Thematic analysis of the transcript of in-depth interview and FGD was performed with the help of Doc Tools in MS Word 2016. RESULTS: The mothers had good knowledge about breastfeeding, importance of colostrum, and weaning practices of infants and children of less than 2 years. Though there is evidence of some cultural misbeliefs, most of the taboos are obsolete now. There was a knowledge gap regarding initiation and composition of complementary feeding practices. The awareness about food diversity, effects of junk food, and recommended complementary feeding practices was less. CONCLUSION: There is need of creating awareness among mothers regarding importance of IYCF practices to reduce infant and under 5 mortality in rural area.

Correlation of weight loss with residual gastric volume on computerized tomography in patients undergoing sleeve gastrectomy: A systematic review.

Laparoscopic Sleeve gastrectomy (LSG) is the most commonly performed bariatric surgical procedure worldwide. There is wide variation however in post-operative weight loss on long term follow-up, and residual gastric volume (RGV) is believed to be an important variable. Multiple studies have correlated RGV as assessed by Computerized Tomography volumetry with excess weight loss (EWL%) following LSG, but definite consensus is lacking. This article systematically reviews the published studies in English literature to ascertain whether any correlation exists between the RGV and EWL% following LSG. Ten studies were included in this review, and significant differences were noted in the technique of RGV assessment, and timing of RGV and EWL% assessment. Five studies found a statistically significant correlation between the RGV and EWL%. One study found a correlation which did not reach statistical significance. Two additional studies reported that the resected volume rather than RGV correlated with the EWL%. Meta-analysis of studies reporting correlation between RGV and EWL% showed that up to 26.3% (95% CI: 5.1%-56.1%) of variability in EWL% can be explained by variations in RGV. A lower RGV is likely to result in a better post-operative weight loss following LSG. There is need for standardization of technique and timing of RGV assessment.

In Vitro Investigation Demonstrates IGFR/VEGFR Receptor Cross Talk and Potential of Combined Inhibition in Pediatric Central Nervous System Atypical Teratoid Rhabdoid Tumors.

BACKGROUND: Atypical teratoid rhabdoid tumor of the central nervous system (CNS ATRT) is a malignancy that commonly affects young children. The biological mechanisms contributing to tumor aggressiveness and resistance to conventional therapies in ATRT are unknown. Previous studies have shown the activity of insulin like growth factor-I receptor (IGF-1R) in ATRT tumor specimens and cell lines. IGF-1R has been shown to cross-talk with other receptor tyrosine kinases (RTKs) in a number of cancer types, leading to enhanced cell proliferation. OBJECTIVE: This study aims to evaluate the role of IGF-1 receptor cross-talk in ATRT biology and the potential for therapeutic targeting. METHODS: Cell lines derived from CNS ATRT specimens were analyzed for IGF-1 mediated cell proliferation. A comprehensive receptor tyrosine kinase (RTK) screen was conducted following IGF-1 stimulation. Bioinformatic analysis of publicly available cancer growth inhibition data to identify correlation between IC50 of a VEGFR inhibitor and IGF-1R expression. RESULTS: Comprehensive RTK screen identified VEGFR-2 cross-activation following IGF-1 stimulation. Bioinformatics analysis demonstrated a positive correlation between IC50 values of VEGFR inhibitor Axitinib and IGF-1R expression, supporting the critical influence of IGF-1R in modulating response to anti-angiogenic therapies. CONCLUSION: Overall, our data present a novel experimental framework to evaluate and utilize receptor cross-talk mechanisms to select effective drugs and combinations for future therapeutic trials in ATRT.

Long noncoding RNAs associated with phenotypic severity in multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a disease that causes progressive neurological disability. Treatments are available that are protective against MS relapses and it is thought that reduction of early neuroinflammation may improve long term prognosis. At present there is no biomarker that can predict which patients may have a more severe disease course, and potentially benefit from more aggressive therapy. Long noncoding RNAs (lncRNAs) are emerging as potential disease biomarkers that could be of interest in prognostication of MS. METHODS: We identified a discovery cohort of 20 patients, ten of which had a mild MS phenotype and ten with severe MS phenotype according to the Age-Related MS Severity Scale (ARMSS). RNAseq was performed on RNA extracted from whole blood and bioinformatic analysis restricted to lncRNAs. Our goal was to select the most significant lncRNAs and quantify these using custom digital droplet RT-qPCR assays in a validation cohort of 44 participants (with mild or severe MS). RESULTS: Eight lncRNA candidates were identified from the discovery cohort. Of these, four lncRNAs remained significantly differentially expressed in the validation cohort (ENSG00000260302, ENSG00000270972, ENSG00000272512 and ENSG00000223387). Little is known about the precise roles of these lncRNAs but based on expression data they appear to be important to immune function and are of potential biological significance to MS pathogenesis. CONCLUSIONS: This study is the first to investigate possible lncRNA biomarkers to differentiate phenotypic severity in MS. Although the findings are preliminary based on our small sample size, they are sufficient to identify hypotheses for future investigation, and give guidance regarding the design of future studies.