Real-world prevalence of adverse events with first-line systemic therapies among patients with metastatic castration-sensitive prostate cancer.

BACKGROUND: The current guidelines for treating metastatic castration-sensitive prostate cancer (mCSPC) recommend treatment intensification of androgen deprivation therapy (ADT) with the addition of an androgen receptor pathway inhibitor (ARPI), with or without docetaxel. However, the adoption of these treatment options has been slow, leading to therapeutic inertia. This real-world study was conducted to investigate the occurrence of adverse events (AEs) among treated patients diagnosed with mCSPC in the United States. METHODS: This retrospective claim review estimated the occurrence of AEs among patients with mCSPC from January 2014 to June 2021 in the PharMetrics® Plus data set. The study focused on 10 common AEs (fatigue/asthenia, gastrointestinal [GI] AEs, skin/nail/hair AEs, immunodeficiency/thrombocytopenia, hot flash, sexual function AEs, anemia, hypertension, pain, and edema) known to occur in ≥10% of patients and ≥2% more prevalent than those treated with ADT alone as selected from the US Food and Drug Administration prescribing information and published results from clinical trials. Proportions of patients experiencing these AEs at Day 90, 180, and then every 180 days until month 30 during the follow-up period were estimated using cumulative hazard plots. Results were adjusted using inverse probability of treatment weighting (IPTW) across four treatment groups: ADT alone, ADT + nonsteroidal anti-androgen (NSAA) (bicalutamide, nilutamide, or flutamide), ADT + docetaxel, and ADT + ARPIs (abiraterone, apalutamide, or enzalutamide). ADT-alone cohort was the reference group for all comparisons. RESULTS: A total of 4145 patients were included (ADT alone: 2318, ADT + NSAA: 632, ADT + docetaxel: 471, ADT + ARPIs: 724). At baseline, median (interquartile range [IQR]) age was 64.3 (60.1-73.1) years; most common sites of metastasis were bone only (n = 1886, 45.5%) and node only (n = 1237, 29.8%); most used medications were pain medications (n = 2182, 52.6%) and corticosteroids (n = 1213, 29.3%). Median (IQR) duration of follow-up 10.2 (6.1-16.6) months in ADT alone, 6.7 (4.1-11.5) months in ADT + NSAA, 5.1 (4.3-5.9) months in ADT + docetaxel, and 11.0 (6.6-17.0) months in ADT + ARPI cohort. The reported AEs increased over time for all assessed AEs, across all treatment groups. Compared with ADT alone, no statistically significant difference in the proportion of patients with AEs was seen in the ADT + ARPI or ADT + NSAA cohorts at months 3 and 12; a significantly higher proportion of patients in the ADT + docetaxel cohort experienced 6 of the 10 assessed AEs at month 3 (fatigue/asthenia, GI AEs, skin/nail/hair AEs, immunodeficiency/thrombocytopenia, hot flash, anemia). During the follow-up period, on IPTW analysis, compared with ADT alone, a significantly higher proportion of patients experienced AEs with seven AEs in the ADT + docetaxel group (fatigue/asthenia, GI AEs, skin/nail/hair AEs, immunodeficiency/thrombocytopenia, hot flash, anemia, edema; p < 0.001 for all seven), three AEs in the ADT + ARPI group (hot flash, p = 0.05; anemia, p = 0.01; edema, p = 0.019), and one AE in the ADT + NSAA group (anemia, p = 0.029). The proportion of patients with sexual function AE did not significantly differ between the treatment groups and ADT alone. CONCLUSION: Results of this large, real-world study demonstrated that all treatment groups experienced an increase in the rates of AEs over time, including ADT alone. Most AE rates with ADT + ARPIs were comparable with ADT + NSAA and not significantly different from ADT alone. ADT + docetaxel cohort was associated with significantly higher rates for all AEs over time except hypertension, sexual dysfunction, and pain. This study provides real-world evidence on AEs, beyond controlled clinical trials, and may assist healthcare providers to make better-informed decisions about disease management among patients with mCSPC.

Endovascular surgical neuro-oncology: advancing a new subspecialty.

Endovascular surgical neuro-oncology is a relatively new subspecialty which uses endovascular neuro-interventional techniques for the management of nervous system tumors and tumor-related vascular conditions. Although there are several endovascular procedures that are widely available as standard-of-care diagnostic and treatment adjuncts, there has been a renewed interest to explore endovascular approaches as a means for selective intra-arterial delivery of therapeutic agents to nervous system tumors, including methods for opening the blood brain and blood tumor barriers. In this review, we discuss the historical development of various forms of endovascular intra-arterial treatment for tumors over the past 40 years, summarize endovascular approaches that are currently being employed, and highlight current clinical trials.

Treatment patterns and outcomes in patients with nonmetastatic castration-resistant prostate cancer in the United States.

Aim: Androgen receptor pathway inhibitors (ARPIs) prolong metastasis-free survival and overall survival in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). This study aimed to evaluate real-world treatment patterns, utilization and survival outcomes in patients with nmCRPC. Patients & methods: This retrospective cohort study used Optum database electronic health records of patients with nmCRPC from 1 January 2007 to 31 December 2020 in the US. Results: Of 1955 patients, >80% received androgen-deprivation therapy (ADT) alone or ADT + first-generation nonsteroidal antiandrogen (NSAA) as first-line treatment, while only 8.24% received ADT + ARPI. ADT + ARPI remained underutilized even among those with high-risk nmCRPC. Further, ADT + NSAA had no survival benefit compared with ADT alone. Conclusion: Practice-improvement strategies are needed for treatment intensification with ARPIs for patients with nmCRPC.

Prostate cancer cells often use hormones called androgens to grow and survive. Hormone therapy is a treatment that lowers the amount of these hormones in the body to slow down the cancer's growth. It includes androgen-deprivation therapy (ADT), which can either be used alone or along with nonsteroidal antiandrogens (NSAAs) or with androgen receptor pathway inhibitors (ARPIs). Nonmetastatic castration-resistant prostate cancer (nmCRPC) is defined as prostate cancer that has not spread to other parts of the body but exhibits rising levels of serum prostate-specific antigen despite surgery or ADT to reduce androgens. Research shows that ARPIs can improve survival in patients with nmCRPC, but more data on its use are needed. This study looked at the electronic health records of patients with nmCRPC to review the treatment they had received and their survival. Between 2008 and 2020, most patients received ADT alone or with NSAA. Even though the number of patients receiving ADT with ARPI increased during this period, it remained underused, even in patients with a high risk of cancer spreading to other body parts. Post-2018, even after 2 years of these drugs being available, only about one in five patients received ADT with ARPI. Also, people who received ADT with NSAA did not have a longer survival than patients treated with ADT alone. The study indicates that ARPIs, which could improve survival of patients with nmCRPC, are not being utilized optimally. Strategies that promote early use of ARPIs are needed to improve survival of patients with nmCRPC.

Guidelines to the Practice of Anesthesia-Revised Edition 2024.

OVERVIEW: The Guidelines to the Practice of Anesthesia-Revised Edition 2024 (the Guidelines) were prepared by the Canadian Anesthesiologists' Society (CAS), which reserves the right to determine their publication and distribution. The Guidelines are subject to revision and updated versions are published annually. The Guidelines to the Practice of Anesthesia-Revised Edition 2024 supersede all previously published versions of this document. Although the CAS encourages Canadian anesthesiologists to adhere to its practice guidelines to ensure high-quality patient care, the CAS cannot guarantee any specific patient outcome. Anesthesiologists should exercise their own professional judgement in determining the proper course of action for any patient's circumstances. The CAS assumes no responsibility or liability for any error or omission arising from the use of any information contained in its Guidelines to the Practice of Anesthesia.

RéSUMé: Le Guide d'exercice de l'anesthésie, version révisée 2024 (le Guide), a été préparé par la Société canadienne des anesthésiologistes (SCA), qui se réserve le droit de décider des termes de sa publication et de sa diffusion. Le Guide est soumis à révision et des versions mises à jour sont publiées chaque année. Le Guide d'exercice de l'anesthésie, version révisée 2024, remplace toutes les versions précédemment publiées de ce document. Bien que la SCA incite les anesthésiologistes du Canada à se conformer à son guide d'exercice pour assurer une grande qualité des soins dispensés aux patient·es, elle ne peut garantir les résultats d'une intervention spécifique. Les anesthésiologistes doivent exercer leur jugement professionnel pour déterminer la méthode d'intervention la mieux adaptée à l'état de leur patient·e. La SCA n'accepte aucune responsabilité ou imputabilité de quelque nature que ce soit découlant d'erreurs ou d'omissions ou de l'utilisation des renseignements contenus dans son Guide d'exercice de l'anesthésie.

Fevers and the social costs of acute infection in wild vervet monkeys.

Fevers are considered an adaptive response by the host to infection. For gregarious animals, however, fever and the associated sickness behaviors may signal a temporary loss of capacity, offering other group members competitive opportunities. We implanted wild vervet monkeys (Chlorocebus pygerythrus) with miniature data loggers to obtain continuous measurements of core body temperature. We detected 128 fevers in 43 monkeys, totaling 776 fever-days over a 6-year period. Fevers were characterized by a persistent elevation in mean and minimum 24-h body temperature of at least 0.5 °C. Corresponding behavioral data indicated that febrile monkeys spent more time resting and less time feeding, consistent with the known sickness behaviors of lethargy and anorexia, respectively. We found no evidence that fevers influenced the time individuals spent socializing with conspecifics, suggesting social transmission of infection within a group is likely. Notably, febrile monkeys were targeted with twice as much aggression from their conspecifics and were six times more likely to become injured compared to afebrile monkeys. Our results suggest that sickness behavior, together with its agonistic consequences, can carry meaningful costs for highly gregarious mammals. The degree to which social factors modulate the welfare of infected animals is an important aspect to consider when attempting to understand the ecological implications of disease.

Guidelines to the Practice of Anesthesia: Revised Edition 2023.

OVERVIEW: The Guidelines to the Practice of Anesthesia Revised Edition 2023 (the Guidelines) were prepared by the Canadian Anesthesiologists' Society (CAS), which reserves the right to determine their publication and distribution. The Guidelines are subject to revision and updated versions are published annually. The Guidelines to the Practice of Anesthesia Revised Edition 2023 supersede all previously published versions of this document. Although the CAS encourages Canadian anesthesiologists to adhere to its practice guidelines to ensure high-quality patient care, the CAS cannot guarantee any specific patient outcome. Anesthesiologists should exercise their own professional judgment in determining the proper course of action for any patient's circumstances. The CAS assumes no responsibility or liability for any error or omission arising from the use of any information contained in its Guidelines to the Practice of Anesthesia.

RéSUMé: Le Guide d'exercice de l'anesthésie, version révisée 2023 (le Guide), a été préparé par la Société canadienne des anesthésiologistes (SCA), qui se réserve le droit de décider des termes de sa publication et de sa diffusion. Le Guide est soumis à révision et des versions mises à jour sont publiées chaque année. Le Guide d'exercice de l'anesthésie, version révisée 2023, remplace toutes les versions précédemment publiées de ce document. Bien que la SCA incite les anesthésiologistes du Canada à se conformer à son guide d'exercice pour assurer une grande qualité des soins dispensés aux patients, elle ne peut garantir les résultats d'une intervention spécifique. Les anesthésiologistes doivent exercer leur jugement professionnel pour déterminer la méthode d'intervention la mieux adaptée à l'état de leur patient. La SCA n'accepte aucune responsabilité ou imputabilité de quelque nature que ce soit découlant d'erreurs ou d'omissions ou de l'utilisation des renseignements contenus dans son Guide d'exercice de l'anesthésie.

Understanding passing network characteristics and their link to match outcome in elite Netball.

Player interactions in Netball are critical during attacking phases of play to ensure possession is maintained and scoring opportunities are created. This study aims to analyse the characteristics of the passing networks of elite Netball teams and their association with performance outcomes (i.e., win/loss and final margin). Five network metrics used to represent the characteristics of teamwork were calculated for all team performances (n = 112) from one season of professional Netball in Australia. A two-way ANOVA and multiple linear modelling were used to compare characteristics between teams and match outcomes and to predict score margin, respectively. Pass density (F = 65.09, df = 102, p < .001) and pass centrality (F = 7.61, df = 102, p < .01) differed (were higher) in wins/losses. They were also statistically significant contributors (p ≤ .005) to the linear model that predicted a score margin (R2 = .731). Key player centrality and mutual connectedness were different between teams but did not differ by match outcome. The results suggest that, ideally, Netball teams should maximise the number of connections between player pairings, while also relying on a subset of players to be heavily involved in passing sequences. Team cohesion (via passing) therefore appears to be an important measure of team success in elite Netball.

Incidence of Infections, Explantations, and Displacements/Mechanical Complications of Spinal Cord Stimulation During the Past Eight Years.

OBJECTIVES: The overall awareness and potential of real-world data have drastically increased in the medical field, with potential implications for postmarket medical device surveillance. The goal of this study was to evaluate real-world data on incidence of infections, explantations, and displacements/mechanical complications of spinal cord stimulation (SCS) during the past eight years and to forecast point estimates for the upcoming three years on the basis of the identified patterns. MATERIALS AND METHODS: Based on electronic health records from 80 healthcare organizations within the TriNetX data base in the USA, data of 11,934 patients who received SCS as treatment for persistent spinal pain syndrome type 2 (PSPS T2) were extracted. Events of interest were explantations and displacements/mechanical complications of both the lead and implanted pulse generator (IPG), in addition to infection rates from 2015 to 2022. Mann-Kendall tests were performed to detect monotonic trends in the time series. Forecasts were conducted for the upcoming three years for every event of interest. RESULTS: Statistically significant increasing time trends were revealed for the annual incidence of IPG and lead displacements/mechanical complications in patients with PSPS T2 over the past eight years. These time trends were visible in both male and female patients and in smokers and nonsmokers. For annual incidence of explantations and infections, no significant time effect was observed. In 2025, the incidence of displacements/mechanical complications of the lead (3.07%) is predicted to be the highest, followed by explantations of the IPG (2.67%) and lead (2.02%). CONCLUSIONS: Based on real world data, device explantation was the most frequent event of interest, with negative peaks in the time series in 2016 and 2020, presumably due to the introduction of rechargeable pulse generators and to the COVID-19 pandemic, respectively.

Benchmarks in colorectal surgery: multinational study to define quality thresholds in high and low anterior resection.

BACKGROUND: Benchmark comparisons in surgery allow identification of gaps in the quality of care provided. The aim of this study was to determine quality thresholds for high (HAR) and low (LAR) anterior resections in colorectal cancer surgery by applying the concept of benchmarking. METHODS: This 5-year multinational retrospective study included patients who underwent anterior resection for cancer in 19 high-volume centres on five continents. Benchmarks were defined for 11 relevant postoperative variables at discharge, 3 months, and 6 months (for LAR). Benchmarks were calculated for two separate cohorts: patients without (ideal) and those with (non-ideal) outcome-relevant co-morbidities. Benchmark cut-offs were defined as the 75th percentile of each centre's median value. RESULTS: A total of 3903 patients who underwent HAR and 3726 who had LAR for cancer were analysed. After 3 months' follow-up, the mortality benchmark in HAR for ideal and non-ideal patients was 0.0 versus 3.0 per cent, and in LAR it was 0.0 versus 2.2 per cent. Benchmark results for anastomotic leakage were 5.0 versus 6.9 per cent for HAR, and 13.6 versus 11.8 per cent for LAR. The overall morbidity benchmark in HAR was a Comprehensive Complication Index (CCI®) score of 8.6 versus 14.7, and that for LAR was CCI® score 11.9 versus 18.3. CONCLUSION: Regular comparison of individual-surgeon or -unit outcome data against benchmark thresholds may identify gaps in care quality that can improve patient outcome.

The thermal consequences of primate birth hour and its evolutionary implications.

Most primates, including humans, give birth during the inactive phase of the daily cycle. Practical constraints therefore limit our knowledge of the precise timing of nocturnal birth in wild diurnal primates and so limit our understanding of selective pressures and consequences. We measured maternal core body temperature (Tb) across 24 births in a population of wild vervet monkeys using biologgers. We identified distinct perturbations in Tb during the birth period, including declining Tb during labour and the rapid recovery of Tb post-parturition. Vervet monkeys typically gave birth during their inactive phase in synchrony with the nadir of the maternal nychthemeral Tb rhythm but also showed remarkable inter-individual variability in their absolute Tb during birth. Our findings support the view that selection may have favoured a nocturnal timing of primate birth to coincide with lower night-time Tb and environmental temperatures, which improve thermal efficiency during birth.

Hand-assisted versus straight laparoscopy for colorectal surgery - a systematic review and meta-analysis.

PURPOSE: Hand-assisted laparoscopic surgery (HALS) is an alternative to straight laparoscopy (LAP) in colorectal surgery. Many studies have compared the two in terms of efficacy, complications, and outcomes. This meta-analysis aims to uncover if there are any significant differences in conversion rates, operative times, body mass index (BMI), incision lengths, intraoperative and postoperative complications, and length of stay. METHODS: Comprehensive searches were performed on databases from their respective inceptions to 16 December 2021, with a manual search performed through Scopus. Randomized controlled trials (RCTs), cohort studies, and case series involving more than 10 patients were included. RESULTS: A total of 47 studies were found fitting the inclusion criteria, with 5 RCTs, 41 cohort studies, and 1 case series. Hand-assisted laparoscopic surgery was associated with lower conversion rates (odds ratio [OR] 0.41, 95%CI 0.28-0.60, p < 0.00001), shorter operative times (Mean Difference [MD] - 8.32 min, 95%CI - 14.05- - 2.59, p = 0.004), and higher BMI (MD 0.79, 95%CI 0.46-1.13, p < 0.00001), but it was also associated with longer incision lengths (MD 2.19 cm, 95%CI 1.66-2.73 cm, p < 0.00001), and higher postoperative complication rates (OR 1.15, 95%CI 1.06-1.24, p = 0.0004). Length of stay was not different in HALS as compared to Lap (MD 0.16 days, 95%CI - 0.06-0.38 days, p = 0.16, and intraoperative complications were the same between both techniques. CONCLUSIONS: Hand-assisted laparoscopy is a suitable alternative to straight laparoscopy with benefits and risks. While there are many cohort studies comparing HALS and LAP, more RCTs would be needed for a better quality of evidence.

Guidelines to the Practice of Anesthesia - Revised Edition 2022.

OVERVIEW: The Guidelines to the Practice of Anesthesia Revised Edition 2022 (the Guidelines) were prepared by the Canadian Anesthesiologists' Society (CAS), which reserves the right to determine their publication and distribution. The Guidelines are subject to revision and updated versions are published annually. The Guidelines to the Practice of Anesthesia Revised Edition 2022 supersedes all previously published versions of this document. Although the CAS encourages Canadian anesthesiologists to adhere to its practice guidelines to ensure high-quality patient care, the CAS cannot guarantee any specific patient outcome. Anesthesiologists should exercise their own professional judgement in determining the proper course of action for any patient's circumstances. The CAS assumes no responsibility or liability for any error or omission arising from the use of any information contained in its Guidelines to the Practice of Anesthesia.

RéSUMé: Le Guide d'exercice de l'anesthésie, version révisée 2022 (le Guide), a été préparé par la Société canadienne des anesthésiologistes (SCA), qui se réserve le droit de décider des termes de sa publication et de sa diffusion. Le Guide est soumis à révision et des versions mises à jour sont publiées chaque année. Le Guide d'exercice de l'anesthésie, version révisée 2022, remplace toutes les versions précédemment publiées de ce document. Bien que la SCA incite les anesthésiologistes du Canada à se conformer à son guide d'exercice pour assurer une grande qualité des soins dispensés aux patients, elle ne peut garantir les résultats d'une intervention spécifique. Les anesthésiologistes doivent exercer leur jugement professionnel pour déterminer la méthode d'intervention la mieux adaptée à l'état de leur patient. La SCA n'accepte aucune responsabilité ou imputabilité de quelque nature que ce soit découlant d'erreurs ou d'omissions ou de l'utilisation des renseignements contenus dans son Guide d'exercice de l'anesthésie.

Effect of Transcatheter Aortic Valve Implantation vs Surgical Aortic Valve Replacement on All-Cause Mortality in Patients With Aortic Stenosis: A Randomized Clinical Trial.

Importance: Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical aortic valve replacement and is the treatment of choice for patients at high operative risk. The role of TAVI in patients at lower risk is unclear. Objective: To determine whether TAVI is noninferior to surgery in patients at moderately increased operative risk. Design, Setting, and Participants: In this randomized clinical trial conducted at 34 UK centers, 913 patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk due to age or comorbidity were enrolled between April 2014 and April 2018 and followed up through April 2019. Interventions: TAVI using any valve with a CE mark (indicating conformity of the valve with all legal and safety requirements for sale throughout the European Economic Area) and any access route (n = 458) or surgical aortic valve replacement (surgery; n = 455). Main Outcomes and Measures: The primary outcome was all-cause mortality at 1 year. The primary hypothesis was that TAVI was noninferior to surgery, with a noninferiority margin of 5% for the upper limit of the 1-sided 97.5% CI for the absolute between-group difference in mortality. There were 36 secondary outcomes (30 reported herein), including duration of hospital stay, major bleeding events, vascular complications, conduction disturbance requiring pacemaker implantation, and aortic regurgitation. Results: Among 913 patients randomized (median age, 81 years [IQR, 78 to 84 years]; 424 [46%] were female; median Society of Thoracic Surgeons mortality risk score, 2.6% [IQR, 2.0% to 3.4%]), 912 (99.9%) completed follow-up and were included in the noninferiority analysis. At 1 year, there were 21 deaths (4.6%) in the TAVI group and 30 deaths (6.6%) in the surgery group, with an adjusted absolute risk difference of -2.0% (1-sided 97.5% CI, -∞ to 1.2%; P < .001 for noninferiority). Of 30 prespecified secondary outcomes reported herein, 24 showed no significant difference at 1 year. TAVI was associated with significantly shorter postprocedural hospitalization (median of 3 days [IQR, 2 to 5 days] vs 8 days [IQR, 6 to 13 days] in the surgery group). At 1 year, there were significantly fewer major bleeding events after TAVI compared with surgery (7.2% vs 20.2%, respectively; adjusted hazard ratio [HR], 0.33 [95% CI, 0.24 to 0.45]) but significantly more vascular complications (10.3% vs 2.4%; adjusted HR, 4.42 [95% CI, 2.54 to 7.71]), conduction disturbances requiring pacemaker implantation (14.2% vs 7.3%; adjusted HR, 2.05 [95% CI, 1.43 to 2.94]), and mild (38.3% vs 11.7%) or moderate (2.3% vs 0.6%) aortic regurgitation (adjusted odds ratio for mild, moderate, or severe [no instance of severe reported] aortic regurgitation combined vs none, 4.89 [95% CI, 3.08 to 7.75]). Conclusions and Relevance: Among patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk, TAVI was noninferior to surgery with respect to all-cause mortality at 1 year. Trial Registration: isrctn.com Identifier: ISRCTN57819173.

Peristomal Necrosis Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Case Report.

BACKGROUND: Peristomal necrosis is a rare but challenging condition requiring multidisciplinary management involving surgical debridement and intensive WOC nurse management. CASE: Mr T was a 56-year-old man who underwent cytoreductive surgery with intraperitoneal chemotherapy for a high-grade appendiceal neoplasm. As part of the procedure, an Abcarian stoma (end-ileostomy with a distal lumen from the transverse colon brought out flush with skin beside the proximal stoma) was created. Postoperatively there was leakage of effluent under the subcutaneous skin resulting in full-thickness necrosis of the peristomal area requiring surgical debridement. Consequently, a large peristomal skin defect occurred, resulting in difficulty achieving a good seal of the ostomy pouching system. To overcome these challenges, a multidisciplinary approach with WOC nurses, colorectal surgeons, and plastic surgeons was implemented. Initially, the defect was managed with a negative pressure wound therapy system, followed by a primary closure of the peristomal skin by the plastic surgeons. Mr T was discharged to home 58 days after his initial surgery; by that time, the peristomal skin was healed and he was able to manage ostomy pouching changes independently. Eight months later his ileostomy was successfully reversed. CONCLUSIONS: Large peristomal defects are challenging but can be managed successfully via a multidisciplinary approach including WOC nurses, colorectal surgeons, and plastic surgeons.

Total Absence of Dystrophin Expression Exacerbates Ectopic Myofiber Calcification and Fibrosis and Alters Macrophage Infiltration Patterns.

Duchenne muscular dystrophy (DMD) causes severe disability and death of young men because of progressive muscle degeneration aggravated by sterile inflammation. DMD is also associated with cognitive and bone-function impairments. This complex phenotype results from the cumulative loss of a spectrum of dystrophin isoforms expressed from the largest human gene. Although there is evidence for the loss of shorter isoforms having impact in the central nervous system, their role in muscle is unclear. We found that at 8 weeks, the active phase of pathology in dystrophic mice, dystrophin-null mice (mdxßgeo) presented with a mildly exacerbated phenotype but without an earlier onset, increased serum creatine kinase levels, or decreased muscle strength. However, at 12 months, mdxßgeo diaphragm strength was lower, whereas fibrosis increased, compared with mdx. The most striking features of the dystrophin-null phenotype were increased ectopic myofiber calcification and altered macrophage infiltration patterns, particularly the close association of macrophages with calcified fibers. Ectopic calcification had the same temporal pattern of presentation and resolution in mdxßgeo and mdx muscles, despite significant intensity differences across muscle groups. Comparison of the rare dystrophin-null patients against those with mutations affecting full-length dystrophins may provide mechanistic insights for developing more effective treatments for DMD.

Can MRI pelvimetry predict the technical difficulty of laparoscopic rectal cancer surgery?

PURPOSE: Selection of an open or minimally invasive approach to total mesorectal excision (TME) is generally based on surgeon preference and an intuitive assessment of patient characteristics but there consensus on criteria to predict surgical difficulty. Pelvimetry has been used to predict the difficult surgical pelvis, typically using only bony landmarks. This study aimed to assess the relationship between pelvic soft tissue measurements on preoperative MRI and surgical difficulty. METHODS: Preoperative MRIs for patients undergoing laparoscopic rectal resection in the Australasian Laparoscopic Cancer of the Rectum Trial (ALaCaRT) were retrospectively reviewed by two blinded surgeons and pelvimetric variables measured. Pelvimetric variables were analyzed for predictors of successful resection of the rectal cancer, defined by clear circumferential and distal resection margins and completeness of TME. RESULTS: There was no association between successful surgery and any measurement of distance, area, or ratio. However, the was a strong association between the primary outcome and the estimated total pelvic volume on adjusted logistic regression analysis (OR = 0.99, P = 0.01). For each cubic centimeter increase in the pelvic volume, there was a 1% decrease in the odds of successful laparoscopic rectal cancer surgery. Intuitive prediction of unsuccessful surgery was correct in 43% of cases, and correlation between surgeons was poor (ICC = 0.18). CONCLUSIONS: A surgeon's intuitive assessment of the difficult pelvis, based on visible MRI assessment, is not a reliable predictor of successful laparoscopic surgery. Further assessment of pelvic volume may provide an objective method of defining the difficult surgical pelvis.

Pediatric hemispherectomy outcome: Adaptive functioning, intelligence, and memory.

OBJECTIVE: Our purpose was to characterize neuropsychological evaluation (NP) outcome following functional hemispherectomy in a large, representative cohort of pediatric patients. METHODS: We evaluated seizure and NP outcomes and medical variables for all post-hemispherectomy patients from Seattle Children's Hospital epilepsy surgery program between 1996 and 2020. Neuropsychological evaluation outcome tests used were not available on all patients due to the diversity of patient ages and competency that is typical of a representative pediatric cohort; all patients had at least an adaptive functioning or intelligence measure, and a subgroup had memory testing. RESULTS: A total of 71 hemispherectomy patients (37 right; 34 females) yielded 66 with both preoperative (PREOP) plus postoperative (POSTOP) NPs and 5 with POSTOP only. Median surgery age was 5.7 (IQR 2-9.9) years. Engel classification indicated excellent seizure outcomes: 59 (84%) Class I, 6 (8%) Class II, 5 (7%) Class III, and 1 (1%) Class IV. Medical variables - including seizure etiology, surgery age, side, presurgical seizure duration, unilateral or bilateral structural abnormalities, secondarily generalized motor seizures - were not associated with either Engel class or POSTOP NP scores, though considerable heterogeneity was evident. Median PREOP and POSTOP adaptive functioning (PREOP n = 45, POSTOP n = 48) and intelligence (PREOP n = 29, POSTOP n = 36) summary scores were exceptionally low and did not reveal group decline from PREOP to POSTOP. Fifty-five of 66 (85%) cases showed stability or improvement. Specifically, 5 (8%) improved; 50 (76%) showed stability; and 11 (16%) declined. Improve and decline groups showed clinically interesting, but not statistical, differences in seizure control and age. Median memory summary scores were low and also showed considerable heterogeneity. Overall median PREOP to POSTOP memory scores (PREOP n = 16, POSTOP n = 24) did not reveal declines, and verbal memory scores improved. Twenty six percent of intelligence and 33% of memory tests had verbal versus visual-spatial discrepancies; all but one favored verbal, regardless of hemispherectomy side. SIGNIFICANCE: This large, single institution study revealed excellent seizure outcome in 91% of all 71 patients plus stability and/or improvement of intelligence and adaptive functioning in 85% of 66 patients who had PREOP plus POSTOP NPs. Memory was similarly stable overall, and verbal memory improved. Medical variables did not predict group NP outcomes though heterogeneity argues for further research. This study is unique for cohort size, intelligence plus memory testing, and evidence of primacy of verbal over visual-spatial development, despite hemispherectomy side. This study reinforces the role of hemispherectomy in achieving good seizure outcome while preserving functioning.

Pelvic exenteration combined with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for advanced primary or recurrent colorectal cancer with peritoneal metastases.

AIM: The aim was to report early outcomes of six patients who underwent combined pelvic exenteration (PE), cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced or recurrent colorectal cancer with colorectal peritoneal metastases at a single centre. The literature contains limited data on the safety and oncological outcomes of patients who undergo this combined procedure. METHODS: Six patients who underwent combined PE, CRS and HIPEC at Royal Prince Alfred Hospital, Sydney, between January 2017 and February 2020 were identified and included. Data were extracted from prospectively maintained databases. RESULTS: Three patients underwent surgery for advanced primary rectal cancer, while two patients had recurrent sigmoid cancer and one had recurrent rectal cancer. All patients had synchronous peritoneal metastases. Two patients required total PE and two patients had a central (bladder-sparing) PE. The median peritoneal carcinomatosis index was 6 (range 3-12) and all patients underwent a complete cytoreduction. The median operating time was 702 min (range 485-900) and the median blood loss was 1650 ml (range 700-12,000). The median length of intensive care unit and hospital stay was 4.5 and 25 days, respectively. There was no inpatient, 30-day or 90-day mortality. Three patients (50%) experienced a major (Clavien-Dindo III/IV) complication. At a median follow-up of 11.5 months (range 2-18 months), two patients died with recurrent disease, one patient was alive with recurrence, while three patients remain alive and disease-free. Of the three patients who developed recurrent disease, one had isolated pelvic recurrence, one had pelvic and peritoneal recurrences and one had bone metastases. CONCLUSION: Early results from this initial experience with simultaneous PE, CRS and HIPEC suggest that this combined procedure is safe and feasible; however, the long-term oncological and quality of life outcomes require further investigation.

Effects of scent enrichment on behavioral and physiological indicators of stress in zoo primates.

Captive breeding is vital for primate conservation, with modern zoos serving a crucial role in breeding populations of threatened species and educating the general public. However, captive populations can experience welfare issues that may also undermine their reproductive success. To enhance the wellbeing of endangered zoo primates, we conducted a study to assess the effects of a new scent enrichment program on captive red-ruffed lemurs (Varecia rubra), black howler monkeys (Alouatta caraya), siamangs (Symphalangus syndactylus), lar gibbons (Hylobates lar) and orangutans (Pongo pygmaeus pygmaeus). We combined behavioral observations and fecal endocrinology analyses to evaluate the effects of a series of essential oils (benzoin, lavender, lemongrass) on five captive troops (N = 19) housed at Dudley Zoo & Castle and Twycross Zoo (UK). We recorded observations of natural species-specific and abnormal stress-related behaviors for 480 h using instantaneous scan sampling. We collected 189 fecal samples and measured the fecal cortisol concentrations using radioimmunoassay. We found a significant effect of the scent enrichment on behaviors, with red-ruffed lemurs and black howler monkeys reducing their social interactions, as well as red-ruffed lemurs and lar gibbons decreasing their stress-related behaviors after they were exposed to the series of essential oils. We also found that red-ruffed lemurs displayed a significant increase in fecal glucocorticoids following exposure to essential oils. Our contradictory findings suggest that the effects of this series of essential oils may change depending on the species-specific social lives and olfactory repertoires of primates. In conclusion, we cannot recommend using these essential oils widely with zoo primates without additional evaluation.

Prognostic significance of subdural hygroma for post-traumatic hydrocephalus after decompressive craniectomy in the traumatic brain injury setting: a systematic review and meta-analysis.

Post-traumatic hydrocephalus (PTH) is a potentially morbid sequela of decompressive craniectomy for traumatic brain injury (TBI). Subdural hygromas are commonly identified following decompressive craniectomy, but the clinical relevance and predictive relationship with PTH in this patient cohort is not completely understood. Survey of seven electronic databases from inception to June 2019 was conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. Multivariate hazard ratios (HRs) for PTH by the presence of subdural hygroma were extracted and pooled by meta-analysis of proportions with random effects modeling. We systematically identified nine pertinent studies describing outcomes of 1010 TBI patients managed by decompressive craniectomy. Of the overall cohort, there were 211 (21%) females and median age was 37.5 years (range 33-53). On presentation, median Glasgow Coma Scale was 7 (range, 5-8). In sum, PTH was reported in 228/840 (27%) cases, and subdural hygroma was reported in 449/1010 (44%) cases across all studies. Pooling multivariate-derived HRs indicated that subdural hygroma was a significant, independent predictor of PTH (HR, 7.1; 95% CI, 3.3-15.1). The certainty of this association was deemed low due to heterogeneity concerns. The presence of subdural hygroma is associated with increased risk of PTH after decompressive craniectomy among TBI patients based on the current literature and may mandate closer clinical surveillance when detected. Prospective studies, including those of intracranial hydrodynamics following decompressive craniectomy in the setting of TBI, will better validate the certainty of these findings.