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Background The financial implications of central nervous system (CNS) cancers are substantial, not only for the healthcare service and payers, but also for the patients who bear the brunt of direct, indirect, and intangible costs. This study sought to investigate the impact of healthcare spending on CNS cancer survival using recent US data. Methods This study used public data from the Disease Expenditure Project 2016 and the Global Burden of Disease Study 2019. The primary outcome was the annual healthcare spending trend from 1996 and 2016 on CNS tumors adjusted for disease prevalence, alongside morbidity and mortality. Secondary outcomes included drivers of change in healthcare expenditures for CNS cancers. Subgroup analysis was performed stratified by age group, expenditure type, and care type provided. Results There was a significant increase in total healthcare spending on CNS cancers from $2.72 billion (95% CI: $2.47B to $2.97B) in 1996 to $6.85 billion (95% CI: $5.98B to $7.57B) in 2016. Despite the spending increase, the mortality rate per 100 000 people increased, with 5.30 ± 0.47 in 1996 and 7.02 ± 0.47 in 2016, with an average of 5.78 ± 0.47 deaths per 100 000 over the period. The subgroups with the highest expenditure included patients aged 45 to 64, those with private insurance, and those receiving inpatient care. Conclusions This study highlights a significant rise in healthcare costs for CNS cancers without corresponding improvements in mortality rate, indicating a mismatch of healthcare spending, contemporary advances, and patient outcomes as it relates to mortality. [ABSTRACT FROM AUTHOR]

Introduction: Laparoscopic sleeve gastrectomy (SG) is the most common bariatric surgical procedure worldwide. Approximately 20%–30% of patients present with weight loss failure or reflux following SG, which might require reoperative surgery. We present the surgical outcomes and complications following reoperative bariatric surgery at a tertiary care centre. Patients and Methods: Prospectively collected data of all patients undergoing reoperative bariatric surgery from 2008 to 2021 were analysed retrospectively. Weight loss, resolution of comorbidities and complications following reoperative surgery were evaluated. Results: Twenty-six patients were included in the study. The mean age was 38.8 (10.8) years. The primary procedure performed was laparoscopic SG in all cases. Nine patients underwent Roux en Y gastric bypass(RYGB) (one banded RYGB) and 14 underwent one anastomosis gastric bypass(OAGB) (three-banded OAGB). Three patients underwent resleeve. The most common indication was weight loss failure (65.3%). Fifteen patients were diagnosed to have hiatal hernia intraoperatively and concomitant repair was performed. The mean body mass index before revision surgery was 42.7 (9.8). It was 32.6 (5.7) kg/m² and 33.0 (6.1) kg/m² at 1 and 3 years, respectively. Age and pre-revision surgery excess weight correlated with weight loss (r = −0.79 and r = 0.99, respectively). Leak and bleeding occurred in one and two patients, respectively. There were two band-related complications and one 30-day mortality. Conclusion: Re-operative bariatric surgery following SG has adequate weight loss with acceptable complication rates. Band placement in re-operative surgery might lead to a higher complication rate. [ABSTRACT FROM AUTHOR]

Background: The association between objective imaging response and first line immune checkpoint inhibitor (ICI) therapy regimes in advanced melanoma remains uncharacterized in routine practice. Methods: We conducted a multi-center retrospective cohort analysis of advanced melanoma patients receiving first line ICI therapy from August 2013-May 2020 in Alberta, Canada. The primary outcome was likelihood of RECIST v1.1 assessed objective imaging response between patients receiving anti-programmed cell death protein 1 (anti-PD1) monotherapy and those receiving combination ipilimumab-nivolumab. Secondary outcomes were identification of baseline characteristics associated with non-response and the association of imaging response with overall survival (OS) and time to next treatment (TTNT). Results: 198 patients were included, 41/198 (20.7%) had complete response, 86/198 (43.4%) had partial response, 23/198 (11.6%) had stable disease, and 48/198 (24.2%) had progressive disease. Median OS was not reached (NR) (95% CI 49.0-NR) months for complete responders, NR (95%CI 52.9-NR) months for partial responders, 33.7 (95%CI 15.8-NR) months for stable disease, and 6.4 (95%CI 5.2–10.1) months for progressive disease (log-rank p<0.001). Likelihood of objective imaging response remained similar between anti-PD1 monotherapy and ipilimumab-nivolumab groups (OR 1.95 95%CI 0.85–4.63, p=0.121). Elevated LDH level (OR 0.46; 95%CI 0.21–0.98, p=0.043), mucosal primary site (OR 0.14; 95%CI 0.03–0.48, p=0.003), and BRAF V600E mutation status (OR 0.31; 95%CI 0.13–0.72, p=0.007) were associated with decreased likelihood of response. Conclusion: No significant difference in likelihood of imaging response between anti-PD1 monotherapy and combination ipilimumab-nivolumab was observed. Elevated LDH level, mucosal primary site, and BRAF V600E mutation status were associated with decreased likelihood of response. Given that pivotal clinical trials of ipilimumab-nivolumab did not formally compare ipilimumab-nivolumab with nivolumab monotherapy, this work adds context to differences in outcomes when these agents are used. These results may inform treatment selection, and aid in counseling of patients treated with first-line ICI therapy in routine clinical practice settings. [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

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. Risk stratification tools for patients with advanced melanoma treated with immune checkpoint inhibitors (ICI) are lacking. This article reports a new prognostic model associated with overall survival, with a focus on clinically accessible parameters available at the start of ICI therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Temporal trends in total and per capita health care spending on kidney cancer stratified by type of care are presented and the primary drivers of change in health expenditures have been determined. Prevalence‐adjusted health care spending steadily increased from $1.18 billion in 1996 to $3.42 billion in 2016 in the United States, which was significantly attributable to inpatient care and driven by the price and intensity of care. There was a substantial increase in prescribed pharmaceutical care to over $360 million in 2007 from less than $2 million in 2006. This period coincided with the years of approval of targeted therapy prescription. [ABSTRACT FROM AUTHOR]

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 underlyingmechanismof 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Citizen science provides an opportunity for the public to contribute to, engage in and learn about science in the context of researchers' construction of scientific knowledge. The following paper explores four undergraduate students' understanding of science inquiry in relation to a citizen science project they developed for high school participants. The findings show that through their involvement in the study and the production of this article, which included a reflective writing and discursive component, the undergraduate students were able to broaden and deepen their notions of science inquiry. The students' development suggests that conceptualizing and implementing a citizen science project with high school students provides a unique platform not just for students' but also for teachers' development in the understanding of science inquiry. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Colchicine is a medication most commonly used in the treatment of gout and familial mediterannean fever. A rare complication of therapy is toxicity causing proximal myopathy and polyneuropathy. Colchicine myopathy has been associated with the coadministration of other medications with colchicine, such as statins or tacrolimus, and is more common in patients with renal impairment. Otherwise, it is unclear which patients are at greatest risk of developing this adverse drug reaction. ABCB1 is important to the metabolism of colchicine, so we speculated that it was possible that colchicine myopathy patients may have a particular genotype that is associated with this side effect. We describe two cases of colchicine myopathy which occurred with co-administration of rosuvastatin. From one case, we present the first published data on muscle MRI in this condition. We additionally present an analysis of four genetic polymorphisms in ABCB1 and transcript levels in muscle tissue, and demonstrate the descriptive finding of reduced ABCB1 transcript levels in the colchicine myopathy patients. [ABSTRACT FROM AUTHOR]

This would help our readers interpret prediction intervals for the effects shown in the forest plot in proper context, as clinicians are more familiar with I I i SP 2 sp . Consequently, the meta-analysis done in the current review [[1]] involves the studies by Fink et al. [[5]] and Bhandari et al. [[7]], both of which have reported weight loss outcomes at 5 years following BSG and SG. [Extracted from the article]