Rye: genetic ancestry inference at biobank scale.

Biobank projects are generating genomic data for many thousands of individuals. Computational methods are needed to handle these massive data sets, including genetic ancestry (GA) inference tools. Current methods for GA inference do not scale to biobank-size genomic datasets. We present Rye-a new algorithm for GA inference at biobank scale. We compared the accuracy and runtime performance of Rye to the widely used RFMix, ADMIXTURE and iAdmix programs and applied it to a dataset of 488221 genome-wide variant samples from the UK Biobank. Rye infers GA based on principal component analysis of genomic variant samples from ancestral reference populations and query individuals. The algorithm's accuracy is powered by Metropolis-Hastings optimization and its speed is provided by non-negative least squares regression. Rye produces highly accurate GA estimates for three-way admixed populations-African, European and Native American-compared to RFMix and ADMIXTURE (${R}^2 = \ 0.998 - 1.00$), and shows 50× runtime improvement compared to ADMIXTURE on the UK Biobank dataset. Rye analysis of UK Biobank samples demonstrates how it can be used to infer GA at both continental and subcontinental levels. We discuss user consideration and options for the use of Rye; the program and its documentation are distributed on the GitHub repository: https://github.com/healthdisparities/rye.

Optimal Surgical Extent for Memory and Seizure Outcome in Temporal Lobe Epilepsy.

OBJECTIVE: Postoperative memory decline is an important consequence of anterior temporal lobe resection (ATLR) for temporal lobe epilepsy (TLE), and the extent of resection may be a modifiable factor. This study aimed to define optimal resection margins for cognitive outcome while maintaining a high rate of postoperative seizure freedom. METHODS: This cohort study evaluated the resection extent on postoperative structural MRI using automated voxel-based methods and manual measurements in 142 consecutive patients with unilateral drug refractory TLE (74 left, 68 right TLE) who underwent standard ATLR. RESULTS: Voxel-wise analyses revealed that postsurgical verbal memory decline correlated with resections of the posterior hippocampus and inferior temporal gyrus, whereas larger resections of the fusiform gyrus were associated with worsening of visual memory in left TLE. Limiting the posterior extent of left hippocampal resection to 55% reduced the odds of significant postoperative verbal memory decline by a factor of 8.1 (95% CI 1.5-44.4, p = 0.02). Seizure freedom was not related to posterior resection extent, but to the piriform cortex removal after left ATLR. In right TLE, variability of the posterior extent of resection was not associated with verbal and visual memory decline or seizures after surgery. INTERPRETATION: The extent of surgical resection is an independent and modifiable risk factor for cognitive decline and seizures after left ATLR. Adapting the posterior extent of left ATLR might optimize postoperative outcome, with reduced risk of memory impairment while maintaining comparable seizure-freedom rates. The current, more lenient, approach might be appropriate for right ATLR. ANN NEUROL 2022;91:131-144.

ProteoVision: web server for advanced visualization of ribosomal proteins.

ProteoVision is a web server designed to explore protein structure and evolution through simultaneous visualization of multiple sequence alignments, topology diagrams and 3D structures. Starting with a multiple sequence alignment, ProteoVision computes conservation scores and a variety of physicochemical properties and simultaneously maps and visualizes alignments and other data on multiple levels of representation. The web server calculates and displays frequencies of amino acids. ProteoVision is optimized for ribosomal proteins but is applicable to analysis of any protein. ProteoVision handles internally generated and user uploaded alignments and connects them with a selected structure, found in the PDB or uploaded by the user. It can generate de novo topology diagrams from three-dimensional structures. All displayed data is interactive and can be saved in various formats as publication quality images or external datasets or PyMol Scripts. ProteoVision enables detailed study of protein fragments defined by Evolutionary Classification of protein Domains (ECOD) classification. ProteoVision is available at http://proteovision.chemistry.gatech.edu/.

What is simulation-based medical education (SBME) debriefing in prehospital medicine? A qualitative, ethnographic study exploring SBME debriefing in prehospital medical education.

INTRODUCTION: Simulation-based medical education (SBME) debriefing - a construct distinct from clinical debriefing - is used following simulated scenarios and is central to learning and development in fields ranging from aviation to emergency medicine. However, little research into SBME debriefing in prehospital medicine exists. This qualitative study explored the facilitation and effects of prehospital SBME debriefing, and identified obstacles to debriefing, using the London's Air Ambulance Pre-Hospital Care Course (PHCC) as a model. METHOD: Ethnographic observations of moulages and debriefs were conducted over two consecutive days of the PHCC in October 2019. Detailed contemporaneous field notes were made and analysed thematically. Subsequently, seven one-to-one, semi-structured interviews were conducted with four PHCC debrief facilitators and three course participants to explore their experiences of prehospital SBME debriefing. Interview data were transcribed and analysed thematically. RESULTS: Four overarching themes were identified: approach to facilitation of debriefs, effects of debriefing, facilitator development, and obstacles to debriefing. The unpredictable debriefing environment was seen as both hindering and, paradoxically, benefitting SBME debriefing. Despite using varied debriefing structures, facilitators emphasised similar key debriefing components including exploring participants' reasoning and sharing experiences to improve learning and prevent future errors. Debriefing was associated with three effects: releasing emotion; learning and improving, particularly compound learning as participants progressed through sequential scenarios; and the application of learning to clinical practice. Facilitator training and feedback were central to facilitator learning and development. Several obstacles to debriefing were identified, including mismatch of participant and facilitator agendas, pressure and time. CONCLUSIONS: SBME debriefing in prehospital medicine is complex, requiring an understanding of participant agendas and facilitator experience to maximise participant learning. Aspects unique to prehospital SBME debriefing were identified, notably, the unpredictable debriefing environment, and the paradoxical benefit of educational obstacles for learning. Aspects of SBME debriefing not extensively detailed in the literature were also highlighted, such as compound participant learning, facilitator candour, and facilitator learning, which require further exploration.

Triacontanol priming as a smart strategy to attenuate lead toxicity in Brassica oleracea L.

The most prevalent heavy metal pollutant in the environment is lead (Pb). Lead potentially contribute 10% of overall heavy metal contamination. Lead uptake by plants has been found to have an impact on their metabolic functions, photosynthetic activity, growth, and productivity. The current experiment was conducted to investigate the impact of triacontanol (Tria) for attenuating Pb stress in Brassica oleracea var. italic (broccoli). Three different Tria concentrations (10, 20 and 30 µmol L-1) were used to prime broccoli seeds. Growth of broccoli was reduced when exposed to Pb-driven toxicity. Additionally, Pb had a deleterious impact on the protein quantity, stomatal conductance, transpiration and photosynthetic rate. Nevertheless, plants grown from seeds primed with Tria2 (20 µmol L-1 Tria) exhibited improved morphological characteristics, uptake of mineral content (Mn+2, Zn+2, K+1, Na+1) along with biomass production. There was 1.6-fold increase in photosynthetic rate, the phenol (1.3 folds), and DPPH activity (1.2 folds) in seed primed with Tria2. Additionally, plants treated with Tria2 demonstrated enhanced MTI and gas exchange characteristics that improves plant stress tolerance under Pb stress. Seed priming with Tria can be used to increase plant tolerance to Pb stress as evidenced by the improved growth and biochemical characteristics of broccoli seedlings.

A number of studies emphasize the beneficial effects of plant growth regulators on the growth and yield of agricultural crops. The priming of seeds with triacontanol in vegetable crops, however, is a concern about which we know remarkably little. In addition, the effects of triacontanol on Brassica oleracea L var. italica under lead stress on growth, biomass, and nutrient content are largely unknown. Thus, the objective of this study was to evaluate the effects of seed priming with triacontanol on the agronomic traits, physiochemical traits, and nutrient content of Brassica oleracea L. var. italica under lead stress.

Exogenous application of glutathione enhanced growth, nutritional orchestration and physiochemical characteristics of Brassica oleracea L. under lead stress.

A major obstacle to agricultural production and yield quality is heavy metal contamination of the soil and water, which leads to lower productivity and quality of crops. The situation has significantly worsened as a result of the growing population and subsequent rise in food consumption. The growth of nutrient-rich plants is hampered by lead (Pb) toxicity in the soil. Brassica oleracea L. (broccoli) is a prominent vegetable crop in the Brassicaceae family subjected to a number of biotic and abiotic stresses that dramatically lower crop yields. Seed priming is a novel, practicable, and cost-effective method that can improve various abiotic stress tolerances. Many plant metabolic activities depend on the antioxidant enzyme glutathione (GSH), which also chelates heavy metals. Keeping in view the stress mitigation potential of GSH, current research work was designed to inspect the beneficial role of seed priming with GSH on the growth, morphological and gas exchange attributes of broccoli seedlings under Pb stress. For this purpose, broccoli seeds were primed with 25, 50, and 75 µM L-1 GSH. Plant growth and photosynthetic activity were adversely affected by Pb stress. Furthermore, Pb stress enhanced proline levels along with reduced protein and phenol content. The application of GSH improved growth traits, total soluble proteins, chlorophyll content, mineral content, and gas exchange parameters. The involvement of GSH in reducing Pb concentrations was demonstrated by an improved metal tolerance index and lower Pb levels in broccoli plants. The results of the current study suggest that GSH can be used as a strategy to increase broccoli tolerance to Pb by enhancing nutrient uptake, growth and proline.

The impact of minimally invasive surgery and frailty on post-hepatectomy outcomes.

BACKGROUND: The impact of patient frailty on post-hepatectomy outcomes is not well studied. We hypothesized that patient frailty is a strong predictor of 30-day post-hepatectomy complications. METHODS: The liver-targeted National Surgical Quality Improvement Program (NSQIP) database for 2014-2019 was reviewed. A validated modified frailty index (mFI) was used. RESULTS: A total of 24,150 hepatectomies were reviewed. Worsening frailty was associated with increased incidence of Clavien-Dindo grade IV complications (mFI 0, 1, 2, 3, 4 was 3.9%, 6.3%, 10%, 8.1%, 50% respectively; p < 0.001). Minimally invasive hepatectomies had a lower rate of Clavien-Dindo grade IV complications for non-frail (Laparoscopic: 1%, Robotic: 2.6%, Open: 4.6%; p < 0.001) and frail patients (Laparoscopic: 3%, Robotic: 2.3%, Open: 7.7%; p < 0.001). Frail patients experienced higher incidence of post-hepatectomy liver failure (5.4% vs 4.1% for non-frail; p < 0.001) and grade C liver failure (28% vs 21.1% for non-frail; p = 0.03). Incorporating mFI to Albumin-Bilirubin score (ALBI) improved its ability to predict Clavien-Dindo grade IV complications (AUC improved from 0.609 to 0.647; p < 0.001) and 30-day mortality (AUC improved from 0.663 to 0.72; p < 0.001). CONCLUSION: Worsening frailty correlates with increased incidence of Clavien-Dindo grade IV complications post-hepatectomy, whereas minimally invasive approaches decrease this risk. Incorporating frailty assessment to ALBI improves its ability to predict major postoperative complications and 30-day mortality.

Awareness about sexually transmitted diseases in women related to their age, education and income.

This study was conducted to assess the level of awareness about sexually transmitted diseases in females of different age groups and to investigate the role that education and social status may play in their knowledge. It was a cross-sectional study, conducted at the CMH Lahore's Gynaecology and Obstetrics out-patient department, from June 2019 till July 2019. Three hundred and thirty-seven participants were interviewed, after obtaining a written informed consent. These participants were females who presented at the CMH Gynaecology & Obstetrics OPD, with any particular complaint. Those who did not give consent were not included in the study. The participants were given a hard copy of the questionnaire to fill and any queries that they had were answered on the spot. Data was analysed using SPSS version 23. Of the 337 participants interviewed, 158 were aged 26-35 years; 71 were undergraduates and 99 had completed post graduate studies. To determine their socioeconomic status, they were asked about their family income; 205 participants belonged to families with an income of less than Rs50,000. Most participants (229) had presented to the OPD for a routine pregnancy check-up. Of the 337 participants, 244 attested to know about STD's and the most common source of their knowledge was through TV (142), followed by the internet (137); 251 participants were familiar with limited STDs such as AIDS and Hepatitis B. The study showed that age, level of education, and income have a profound effect on the knowledge regarding sexually transmitted diseases amongst the women in Pakistan.

Phase I trial of low-dose interleukin 2 therapy in patients with Wiskott-Aldrich syndrome.

BACKGROUND: Low dose IL-2 can restore the function of T and NK cells from Wiskott-Aldrich (WAS) patients. However, the safety of in vivo IL-2 in WAS is unknown. OBJECTIVES: A phase-I study to assess safety of low dose IL-2 in WAS. METHODS: Patients received 5 daily subcutaneous IL-2 injections, every 2months, for three courses. A "3+3" dose escalation method was used. RESULTS: 6 patients received the 0.5millionunits/m2/day dose without serious adverse events. However, 2 of 3 patients receiving the 1millionunits/m2/day dose developed thrombocytopenia requiring platelet transfusions. A statistically significant platelet increase occurred in patients receiving the 0.5millionunits/m2/day dose. A trend toward higher T, B and NK cell numbers and higher T regulatory cell percentages was observed. CONCLUSION: We have identified a safe IL-2 dose for WAS patients. Additional trials are indicated to study the efficacy of this immunostimulant as a therapy for WAS.

Resourcing the arts for youth well-being: challenges in Aotearoa New Zealand.

BACKGROUND: This paper synthesises findings from two research projects with organisations involved in arts for youth well-being. Since 2017, Aotearoa New Zealand's government has recognised the importance of the arts for well-being. However, the sector in Aotearoa has historically lacked recognition and support and this paper identifies a number of challenges that remain entrenched in the funding system. METHODS: Study One used an online survey to understand the approaches, aspirations and challenges of 19 organisations involved in youth arts for well-being. Study Two used ethnographic methods with three youth arts organisations to explore their experiences of the funding and policy context. RESULTS: Specific aspects of the funding system in Tamaki Makaurau, Auckland, hinder the sustainable development of creatively rich, culturally responsive, inclusive and strengths-based practice that takes youth participation seriously. CONCLUSIONS: New approaches to resourcing youth arts for well-being are needed to better support good practice and sector development.

One- versus two-stage conversions of adjustable gastric bands: an analysis of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database.

BACKGROUND: Laparoscopic adjustable gastric bands (AGB) are converted at high rates to secondary bariatric procedures. The available literature on the safety of converting in 1- versus 2-stage processes has not included large databases. OBJECTIVE: To evaluate the safety of a 1- versus 2-stage conversion of AGB. SETTING: Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP), United States. METHODS: The MBSAQIP database for the years 2020 and 2021 was evaluated. One-stage AGB conversions were identified using Current Procedural Terminology codes and database variables. Multivariable analysis was performed to determine whether 1- or 2-stage conversions were associated with 30-day serious complications. RESULTS: There were 12,085 patients who underwent conversion from previous AGB to sleeve gastrectomy (SG) (63.0%) or Roux-en-Y gastric bypass (RYGB) (37.0%), of whom 41.0% underwent conversion in 1 stage and 59.0% in 2 stages. Patients who underwent 2-stage conversions had higher body mass indexes. Rates of serious complications were higher for patients undergoing RYGB compared with SG (5.2% versus 3.3%, P < .001) but were similar between 1-stage and 2-stage conversions in both cohorts. In both cohorts, there were similar rates of anastomotic leaks, postoperative bleeding, reoperation, and readmissions. Mortality was rare and similar between conversion groups. CONCLUSIONS: There was no difference in outcomes or complications in 30 days between 1- and 2-stage conversions of AGB to RYGB or SG. Conversions to RYGB have higher complication and mortality rates than to SG, but there was no statistically significant difference between staged procedures. One- and 2-stage conversions from AGB are equivalent in safety.

When do leaks occur? An analysis of the metabolic and bariatric surgery accreditation and quality improvement program.

BACKGROUND: Leak is a feared complication of bariatric surgeries. Time to presentation is important in their management. We used the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) to evaluate the rate and timing of leaks. OBJECTIVES: To determine when leaks present after bariatric surgery. SETTING: MBSAQIP database. METHODS: The MBSAQIP Participant Use Files (PUF) for the years 2015-2020 were evaluated. Outcomes of interest were "organ space infection" and "leak." We evaluated the time to presentation for these variables as well as patient characteristics, operative time, complication rates and 30-day outcomes. RESULTS: There were 370,369 sleeve gastrectomies (SG) and 159,280 Roux-en-Y gastric bypasses (RYGB). We identified 598 (.16%) SG leaks with an average time to presentation of 13.2 ± 7.8 days. For RYGB, there were 520 leaks (.32%) with an average time to presentation of 9.5 ± 7.4 days. Both procedures had longer operative times for the patients with leak; RYGB was 115 minutes versus 131 minutes and SG was 67 minutes versus 77 minutes (both P < .01). SG and RYGB patients with a leak had a higher relative risk (RR) of grade 4 and 5 Clavien-Dindo complication rates. RR of mortality rates in SG patients with leak was 35.2 (confidence interval (CI): 20-61) and in RYGB with leak was 31.4 (CI: 19-50). CONCLUSIONS: The length of time for SG leak presentation was more delayed than RYGB leak presentation. Surgeons should be vigilant for leaks for at least 3 weeks after surgery. Leaks increase the mortality rate and overall serious complications.

Stapler Malfunctions in Bariatric Surgery: An Analysis of the MAUDE Database.

Background: Staple line leaks are a serious problem in bariatric surgery and a major cause of serious morbidity and mortality. Adverse events caused by medical devices are reported to the Food and Drug Administration which maintains the Manufacturer and User Facility Device Experience (MAUDE) database. We examined adverse stapler events reported to the MAUDE database, specifically with regards to bariatric surgery. Methods: The MAUDE database was queried for adverse events caused by staplers between January 1, 2018 - December 31, 2020; events reported by Intuitive, Ethicon, and Medtronic/Covidien; and limited our search to "gastric bypass", "sleeve gastrectomy", "stapler malfunction" combined with each company. Results: There were 883 adverse events reported for Medtronic, 353 for Ethicon, and 35 for Intuitive. Approximately 3.5 million staple reloads sold in the study period. The reported misfire rate for Medtronic was 0.04% and for Ethicon was 0.02%. Data for Intuitive was unavailable. The most common reported event for Medtronic was failure to fire (n = 349), followed by misfire (n = 186). For Ethicon, the most common event was failure to fire (n = 146), followed by mechanical problems (n = 27). The most common event with the Intuitive stapler was leak (n = 10) and bleeding from staple line (n = 8). Conclusions: Stapler malfunction is a very rare event in metabolic and bariatric surgery. All of the major stapler producers have transitioned to powered staplers with excellent safety profiles. Open and honest reporting about stapler malfunction is essential to determine the true safety of these ubiquitous devices.

Facility Type Affects Treatment Outcomes for Patients With Mucinous Cystic Neoplasms and Intraductal Papillary Mucinous Neoplasms of the Pancreas.

OBJECTIVE: Academic centers report better outcomes for pancreatic ductal adenocarcinoma. We hypothesized that treatment outcomes for mucinous cysts differ according to institution type. METHODS: Using the National Cancer Data Base, we analyzed data on patients with mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs). RESULTS: Of 3278 identified patients, 2622 (80%) had IPMNs and 656 (20%) had MCNs. While most academic/research programs (ARCPs, 84.9%) treated more than 10 patients/year, this was true for only 59% of integrated network cancer programs, 37.3% of comprehensive community cancer programs, and 0% of community cancer programs (P < 0.001). Surgery was used more often in ARCPs and for smaller tumors. The ARCPs had higher rates of margin negative resections with retrieval of 15 or more nodes with the lowest 30- and 90-day mortality rates. The median overall survival was better in ARCPs (110.3 months) than comprehensive community cancer programs (75.1 mo), community cancer programs (75.1 mo), or integrated network cancer programs (100.8 mo, P < 0.001). CONCLUSIONS: Treatment of MCNs and IPMNs of the pancreas at academic centers is associated with a higher probability of pancreatectomy, disease identification in a noninvasive stage, and better overall survival. Centralization of care for mucinous pancreatic cysts will lead to improved outcomes.

Vitamin D and socioeconomic deprivation mediate COVID-19 ethnic health disparities.

Ethnic minorities in developed countries suffer a disproportionately high burden of COVID-19 morbidity and mortality, and COVID-19 ethnic disparities have been attributed to social determinants of health. Vitamin D has been proposed as a modifiable risk factor that could mitigate COVID-19 health disparities. We investigated the relationship between vitamin D and COVID-19 susceptibility and severity using the UK Biobank, a large progressive cohort study of the United Kingdom population. Structural equation modelling was used to evaluate the ability of vitamin D, socioeconomic deprivation, and other known risk factors to mediate COVID-19 ethnic health disparities. Asian ethnicity is associated with higher COVID-19 susceptibility, compared to the majority White population, and Asian and Black ethnicity are both associated with higher COVID-19 severity. Socioeconomic deprivation mediates all three ethnic disparities and shows the highest overall signal of mediation for any COVID-19 risk factor. Vitamin supplements, including vitamin D, mediate the Asian disparity in COVID-19 susceptibility, and serum 25-hydroxyvitamin D (calcifediol) levels mediate Asian and Black COVID-19 severity disparities. Several measures of overall health also mediate COVID-19 ethnic disparities, underscoring the importance of comorbidities. Our results support ethnic minorities' use of vitamin D as both a prophylactic and a supplemental therapeutic for COVID-19.

Impact of facility type on survival after pancreatoduodenectomy for small pancreatic adenocarcinoma (≤ 2 cm).

BACKGROUND: Previous studies have demonstrated that even small pancreatic cancers are associated with poor survival. The role of facility type on survival in this setting is unknown. STUDY DESIGN: The National Cancer Database (NCDB) was utilized. Patients who underwent pancreatoduodenectomy for adenocarcinoma ≤ 2 cm in Academic/Research Cancer Programs (ACPs) were compared to Non-Academic Cancer Programs (NACPs). RESULTS: A total of 4672 patients were identified. Surgery at ACPs was associated with a lower rate of positive margins (14% vs 17%,P < .0001) and a higher rate of lymphadenectomy ≥15 nodes (49.6% vs 36.3%,P < .0001). Over 75% of the ACPs facilities were high volume vs 25.5% among NACPs. There was no difference in the odds of delivering chemotherapy in the neoadjuvant or adjuvant setting between ACPs and NACPs. The median survival at ACPs was 29.4 months vs 25.7 months at NACPs (Log-rank test:P < .0001). ACPs were associated with improved survival, adjusted Hazard Ratio: 0.88, 95%CI:0.81-0.96. CONCLUSION: Pancreatoduodenectomy for small pancreatic cancers at ACPs is associated with improved survival compared to NACPs.

The Impact of the COVID-19 Pandemic on Resident Physicians Well-Being in the Surgical and Primary Care Specialties in the United States and Canada.

PURPOSE:  The COVID-19 pandemic disrupted the professional, social, and spiritual activities of resident physicians around the world, impacting wellness and personal relationships. Moreover, social distancing caused significant limitations or shutdown of places of worship, including churches, synagogues, mosques, etc. Our goal was to survey resident physicians in primary care and surgical subspecialties in the United States (U.S.) and Canada and to examine the effect of the COVID-19 pandemic on their well-being. METHODS:  An international cross-sectional study was performed in November 2020, using an anonymous survey of programs in the U.S. and Canada, containing 20 questions to assess the impact of the pandemic on resident participation in social and spiritual activities and the effects on their wellness, and personal relationships. The emails with survey links attached were sent to individual program coordinators from accredited residency training programs in the United States and Canada. This consisted of programs accredited by the American Osteopathic Association (AOA), The Royal College of Physicians and Surgeons of Canada (RCPSC), and the Accreditation Council of Graduate Medical Education (ACGME). The survey was evenly divided among surgical programs (General Surgery, Neurological Surgery, Orthopedic Surgery, Urological Surgery, and Integrated Surgical Residency Programs such as Plastic Surgery, Cardiothoracic Surgery, Pediatric Surgery, and Vascular Surgery) as well as primary care programs (Internal Medicine and Family Medicine). RESULTS:  A total of 196 residents, 60 primary care residents, and 136 surgery residents participated in the study. Ninety-six participants (49%) were female, and 98 of the participants (50%) were male, with the remainder two residents identifying as "Other." Of the primary care residents, the majority (39, 65%) were female. Conversely, the majority (77, 57%) of surgery residents were male. CONCLUSION:  The COVID-19 pandemic has affected the social lives, relationships, and spiritual well-being of both surgical and primary care resident physicians. However, primary care residents reported significantly greater engagement in personal relationships and were more likely to express feelings of mental and physical exhaustion, prohibiting social attendance.

Mucinous cystic neoplasms of the pancreas in the modern era. Experience with 707 patients.

BACKGROUND: Mucinous Cystic Neoplasms are mucin producing cysts of the pancreas with malignant potential. The existing literature on treatment outcomes is limited to relatively small surgical series. METHODS: We reviewed the National Cancer Database assessing the outcomes of patients with mucinous cystic neoplasms between 2004 and 2016. Kaplan-Meier method and log rank test were used to make survival comparisons. RESULTS: A total of 707 patients were identified; 492(69.6%) underwent pancreatectomies. The majority of patients were women (71.4%), with median age 65 years (range: 22-90). Most common operation was partial pancreatectomy ie distal (48.4%) whereas 21.7% underwent a Whipple. Patients who were not operated were more frequently stage IV (40%) whereas patients who were operated had more frequently invasive adenocarcinoma (74.8%). Patients who underwent pancreatectomy had better survival compared to these who didn't undergo surgery (81.4 vs 6.6 months; p < 0.001). Comparing patients who underwent pancreatectomy and had invasive disease versus patients who had in situ disease the former were older (median age 62 vs 55.5 years p = 0.004) and more frequently men (26.1 vs 16.1%; p = 0.03), however they had similar tumor size (5.5 vs 7 cm respectively; p = 0.14) and similar tumor differentiation (moderately differentiated 50% vs 38.1%; p = 0.49). Patients with non-invasive (in situ) disease had prolonged survival compared to these with invasive disease (median OS not reached vs 50.2months; p < 0.001). After Cox proportional hazard regression nodal positive disease was the most important factor of decreased survival for invasive adenocarcinoma (HR: 2.2; p < 0.001). CONCLUSION: Patients with adenocarcinoma arising from a mucinous cystic neoplasm of the pancreas have excellent survival when they undergo pancreatectomy especially if the disease is still in situ. However, 3/4 of patients who undergo resection have already developed invasive adenocarcinoma and nodal status dominates their prognosis. Advanced age but not the size of the cyst correlate with the presence of invasive disease.

Diagnostic accuracy of a revised computed tomography angiography score for brain death confirmation, combining supra-tentorial arteries and infra-tentorial veins.

PURPOSE: The 4-point score is the corner stone of brain death (BD) confirmation using computed tomography angiography (CTA). We hypothesized that considering the superior petrosal veins (SPVs) may improve CTA diagnosis performance in BD setting. We aimed at comparing the diagnosis performance of three revised CTA scores including SPVs and the 4-point score in the confirmation of BD. METHODS: In this retrospective study, 69 consecutive adult-patients admitted in a French University Hospital meeting clinical brain death criteria and receiving at least one CTA were included. CTA images were reviewed by two blinded neuroradiologists. A first analysis compared the 4-point score, considered as the reference and three non-opacification scores: a "Toulouse score" including SPVs and middle cerebral arteries, a "venous score" including SPVs and internal cerebral veins and a "7-score" including all these vessels and the basilar artery. Psychometric tools, observer agreement and misclassification rates were assessed. A second analysis considered clinical examination as the reference. RESULTS: Brain death was confirmed by the 4-score in 59 cases (89.4 %). When compared to the 4-score, the Toulouse score displayed a 100 % positive predictive value, a substantial observer agreement (0.77 [0.53; 1]) and the least misclassification rate (3.03 %). Results were similar in the craniectomy subgroup. The Toulouse score was the only revised test that combined a sensitivity close to that of the 4-score (86.4 % [75.7; 93.6] and 89.4 % [79.4; 95.6], p-value < 0.001, respectively) and a substantial observer agreement. CONCLUSIONS: A score including SPVs and middle cerebral arteries is a valid method for BD confirmation using CTA even in patients receiving craniectomy.

Development and validation of an HPLC-UV method for accelerated stability study and pharmacokinetic analysis of venlafaxine

A reverse phase high performance liquid chromatography method has been developed and validated for accelerated stability study and determination of pharmacokinetic parameters of venlafaxine HCl. The chromatographic separation was carried out using ODS analytical column (250 × 4.6 mm i.d., 5 µm particle size). The mobile phase included acetonitrile, methanol and potassium dihydrogen phosphate buffer (30:30:40; pH 6.1) at a flow rate 1.5 mL min−1. UV-Visible detector was used at wavelength of 227 nm to monitor elutions. Retention time observed was 2.745 min. The method was validated for linearity, accuracy, precision, sensitivity and robustness. Accelerated stability study of venlafaxine HCl capsules was carried out at 40 and 50 ºC under 75% RH level. Suggested method was successfully applied for the pharmacokinetic analysis of venlafaxine hydrochloride tablets. Each of ten albino rabbits (≈ 1.2 kg each) was orally administered with 5 mg dose of venlafaxine HCl. The method was proved to be linear (R2 >0.998), accurate (98.25-99.27%), sensitive (LOD: 35ngmL−1; LOQ: 105 ng mL−1) and robust (RSD<1%). The drug showed stability at accelerated conditions of temperature and humidity. The main pharmacokinetic parameters of tested products were as follows: tmax was 2.5h, Cmax was 56.5 µg mL−1, t1/2 was 8.2 h, AUC0-36 was 845.9 µg h mL−1. The developed method is suitable to apply for quality control analysis and pharmacokinetic studies.