Search

Septic shock is associated with a mortality of 20-40%. The white blood cell count (WBC) at hospital admission correlates with prognosis in septic shock. Here, we explore whether the trajectory of WBC after admission provides further information about outcomes. We aimed to identify groups of patients with different WBC trajectories and the association of WBC trajectory with mortality.We included adult patients with septic shock in two academic intensive care units (ICU) in Winnipeg, MB, Canada between 2006 and 2012. We used group-based trajectory analysis to group patients according to their WBC patterns over the first seven days in the ICU. Our primary analysis was the association of WBC trajectory group on 30-day mortality using multivariable Cox proportional hazards regression.We included 917 patients with septic shock. The final model identified seven distinct WBC trajectories. The rising WBC trajectory was independently associated with increased mortality (hazard ratio, 3.41; 95% confidence interval, 1.86 to 6.26; P0.001) compared with the stable WBC trajectory.In patients with septic shock, distinct and clinically relevant groups can be identified by analyzing WBC trajectories. A rising WBC trajectory was associated with higher mortality.RéSUMé: OBJECTIF: Le choc septique est associé à une mortalité de 20 à 40 %. La numération leucocytaire à l’admission à l’hôpital est corrélée au pronostic en cas de choc septique. Dans ce manuscrit, nous tentons de déterminer si l’évolution de la numération leucocytaire après l’admission fournit plus d’informations sur les devenirs. Nous avons cherché à identifier des groupes de patients présentant différentes trajectoires d’évolution de numération leucocytaire et l’association entre l’évolution de la numération et la mortalité. MéTHODE: Nous avons inclus des patients adultes atteints d’un choc septique dans deux unités de soins intensifs (USI) universitaires à Winnipeg, Manitoba, Canada entre 2006 et 2012. Nous avons utilisé une analyse de l’évolution basée sur le groupe pour regrouper les patients en fonction du type d’évolution de la numération leucocytaire au cours des sept premiers jours à l’USI. Notre analyse principale consistait à déterminer l’association entre le groupe d’évolution de numération leucocytaire et la mortalité à 30 jours en utilisant une régression multivariable à risque proportionnel de Cox. RéSULTATS: Nous avons inclus 917 patients atteints de choc septique. Le modèle final a identifié sept types de trajectoire d’évolution de numération leucocytaire distincts. Une évolution ascendante de la numération leucocytaire était indépendamment associée à une augmentation de la mortalité (rapport de risque, 3,41; intervalle de confiance à 95 %, 1,86 à 6,26; P0,001) par rapport à une évolution de numération leucocytaire stable. CONCLUSION: Chez les patients atteints de choc septique, des groupes distincts et cliniquement pertinents peuvent être identifiés en analysant les trajectoires d’évolution de la numération leucocytaire. Une évolution ascendante de la numération leucocytaire était associée à une mortalité plus élevée.

Background: Major societal guidelines recommend a 5-day stop interval before cardiac surgery for patients with acute coronary syndrome receiving clopidogrel. Yet, many such patients present with high acuity, generating surgeon inclination toward use of shorter stop intervals. Thus, this study aimed to determine the impact of the duration and timing of the interval of clopidogrel cessation on adverse bleeding events. Methods: Patients who underwent cardiac surgery between 2009 and 2016 at a tertiary-care centre were included in this retrospective cohort study. Multivariable logistic regression models adjusted for clopidogrel stop interval, age, urgency of procedure, and procedure type were used to quantify the effect of clinically relevant baseline demographic characteristics on incidence of massive transfusion as well as hemorrhagic complication outcomes. Results: A total of 5748 patients underwent cardiac surgery. In this cohort, 1743 patients (30.3%) received clopidogrel preoperatively, and 884 (50.7%) of these patients discontinued clopidogrel 5 days before presenting to the operating room. The administration of clopidogrel 1-2 days before surgery (odds ratio 1.97; 95% confidence interval: 1.18 to 3.29) was an independent predictor for massive transfusions and hemorrhagic complications (odds ratio 1.85; 95% confidence interval: 1.01 to 3.37). The 3-4 day group did not have an increased risk of major bleeding complications. The risk for both massive transfusions and hemorrhagic complications also increased with the urgency and complexity of surgery. Conclusion: A clopidogrel stop interval of 3-4 days preoperatively was not associated with an increased risk for major bleeding complications. Résumé: Introduction: Les grandes lignes directrices sociétales recommandent une interruption de cinq jours avant l’intervention chirurgicale du cœur des patients atteints d’un syndrome coronarien aigu qui prennent du clopidogrel. Toutefois, comme il s’agit pour plusieurs d’entre eux de patients de haute acuité, le chirurgien penche vers l’utilisation d’une interruption plus courte. Par conséquent, la présente étude avait pour objectif de déterminer les conséquences de la durée et du moment de la cessation du clopidogrel sur les événements hémorragiques indésirables. Méthodes: La présente étude de cohorte rétrospective portait sur les patients qui avaient subi une intervention chirurgicale au cœur entre 2009 et 2016 dans un centre de soins tertiaires. Nous avons utilisé les modèles multivariés de régression logistique ajustés à l’interruption du clopidogrel, à l’âge, à l’urgence de l’intervention chirurgicale et au type d’intervention chirurgicale pour quantifier les effets des caractéristiques démographiques initiales cliniquement pertinentes sur la fréquence des transfusions massives ainsi que sur les issues des complications hémorragiques. Résultats: Un total de 5 748 patients ont subi une intervention chirurgicale au cœur. Dans cette cohorte, parmi les 1 743 patients (30,3 %) qui avaient reçu du clopidogrel avant l’opération, 884 (50,7 %) avaient cessé le clopidogrel cinq jours avant leur admission à la salle d’opération. L’administration du clopidogrel un à deux jours avant l’intervention chirurgicale (ratio d’incidence approché 1,97; intervalle de confiance [IC] à 95 % : de 1,18 à 3,29) était un prédicteur indépendant des transfusions massives et des complications hémorragiques (ratio d’incidence approché 1,85; [IC] à 95 % : de 1,01 à 3,37). Le groupe de l’interruption de trois à quatre jours n’a pas montré de risque accru de complications hémorragiques graves. Le risque de transfusions massives et de complications hémorragiques a aussi contribué à l’augmentation de l’urgence et de la complexité de l’intervention chirurgicale. Conclusion: Une interruption du clopidogrel de trois à quatre jours avant l’opération n’a pas été associée à un risque accru de complications hémorragiques graves.

Aims Orthopaedic surgeries are complex, frequently performed procedures associated with significant haemorrhage and perioperative blood transfusion. Given refinements in surgical techniques and changes to transfusion practices, we aim to describe contemporary transfusion practices in orthopaedic surgery in order to inform perioperative planning and blood banking requirements. Methods We performed a retrospective cohort study of adult patients who underwent orthopaedic surgery at four Canadian hospitals between 2014 and 2016. We studied all patients admitted to hospital for nonarthroscopic joint surgeries, amputations, and fracture surgeries. For each surgery and surgical subgroup, we characterized the proportion of patients who received red blood cell (RBC) transfusion, the mean/median number of RBC units transfused, and exposure to platelets and plasma. Results Of the 14,584 included patients, the most commonly performed surgeries were knee arthroplasty (24.8%), hip arthroplasty (24.6%), and hip fracture surgery (17.4%). A total of 10.3% of patients received RBC transfusion; the proportion of patients receiving RBC transfusions varied widely based on the surgical subgroup (0.0% to 33.1%). Primary knee arthroplasty and hip arthroplasty, the two most common surgeries, were associated with in-hospital transfusion frequencies of 2.8% and 4.5%, respectively. RBC transfusion occurred in 25.0% of hip fracture surgeries, accounting for the greatest total number of RBC units transfused in our cohort (38.0% of all transfused RBC units). Platelet and plasma transfusions were uncommon. Conclusion Orthopaedic surgeries were associated with variable rates of transfusion. The rate of RBC transfusion is highly dependent on the surgery type. Identifying surgeries with the highest transfusion rates, and further evaluation of factors that contribute to transfusion in identified at-risk populations, can serve to inform perioperative planning and blood bank requirements, and facilitate pre-emptive transfusion mitigation strategies. Cite this article: Bone Jt Open 2021;2(10):850–857.

Objective Exercise is recommended for polycystic ovary syndrome (PCOS), but the most effective exercise prescription is unclear. This trial compared effects of high‐intensity interval training (HIIT), continuous aerobic exercise training (CAET) and no‐exercise control on reproductive, anthropometric and cardiometabolic outcomes in PCOS. Design Pilot randomized controlled trial. Participants Previously inactive women aged 18–40 years with PCOS. Measurements Feasibility outcomes included recruitment, retention, adherence to exercise and daily ovulation prediction kit (OPK) testing. Preliminary efficacy outcomes included reproductive, anthropometric and cardiometabolic health markers. Results Forty‐seven women were randomized to no‐exercise control (n = 17), HIIT (n = 16), or CAET (n = 14). Forty (85%) participants completed the trial. Median exercise adherence was 68% (IQR 53%, 86%). Median daily OPK‐testing adherence in the first half of the intervention was 87% (IQR 61%, 97%) compared with 65% (IQR 0%, 96%) in the second half. Body mass index decreased significantly in CAET compared with control (−1.0 kg/m2, p = .01) and HIIT (−0.9 kg/m2, p = .04). Mean waist circumference decreased in all groups (−7.3 cm, −6.9 cm, −4.5 cm in HIIT, CAET and control) with no significant between‐group differences. Mean LDL‐C was significantly reduced for HIIT compared to CAET (−0.33 mmol/L, p = .03). HDL‐C increased in HIIT compared with control (0.18 mmol/L, p = .04). Conclusions There were feasibility challenges with adherence to daily ovulation assessment limiting the ability to analyse the effect of the exercise interventions on ovulation. CAET and HIIT were both effective at improving anthropometrics and some cardiometabolic health markers. Further studies need to determine optimal and acceptable exercise prescriptions for this population.

OBJECTIVE To determine the predictors of postoperative acute kidney injury (AKI) following nonemergent cardiac surgery among patients with variable preoperative estimated glomerular filtration rate (eGFR) levels. METHODS A retrospective study of patients who underwent elective or in-hospital cardiac surgical procedures was performed between January 2006 and November 2015. The procedures included isolated coronary artery bypass grafting (CABG), isolated aortic valve replacement (AVR), or combined CABG and AVR. The primary outcome AKI (any stage) following nonemergent cardiac surgery utilizing the 2012 Kidney Disease-Improving Global Outcomes (KDIGO) criteria. Patients were categorized based on the following renal outcomes: mild AKI, severe AKI (KDIGO stage 2 or 3), and postoperative dialysis. Patients with G5 preoperative kidney function (including dialysis patients) were excluded. RESULTS A total of 6675 patients were included in our study. The mean age was 66.8 years (SD ± 10.4), with 76.3% being males. A total of 4487 patients had normal or mildly decreased eGFR (G1 or G2) preoperatively (67.2%), while 1960 patients were in the G3 category (29.4%). Only 228 patients (3.4%) had G4 renal function. A total of 1453 (21.7%) patients experienced postoperative AKI. The need for postoperative dialysis occurred in 3.2% of the AKI subgroup. In-hospital mortality was higher among the AKI subgroup (7.2% vs. 0.5%; p

To evaluate the incremental impact of resistance training on HbA1c, fitness, body composition and cardiometabolic risk factors in aerobically-active people with type 1 diabetes.The Resistance Exercise in Already-active Diabetic Individuals (READI) trial (NCT00410436) was a four-centre randomized parallel-group trial. After a 5-week run-in period with diabetes management optimization, 131 aerobically-active individuals with type 1 diabetes were randomized to resistance exercise (n = 71, intervention - INT) or control (n = 60, CON) for 22 additional weeks. Both groups maintained their aerobic activities and were provided dietary counselling throughout. Exercise training was three times per week at community-based facilities. The primary outcome was HbA1c, and secondary outcomes included fitness (peak oxygen consumption, muscle strength), body composition (anthropometrics, dual-energy X-ray absorptiometry, computed tomography) and cardiometabolic risk markers (lipids, apolipoproteins). Assessors were blinded to group allocation.There were no significant differences in HbA1c change between INT and CON. Declines in HbA1c [INT: 7.75 ± 0.10% (61.2 ± 1.1 mmol/mol) to 7.55 ± 0.10% (59 ± 1.1 mmol/mol); CON: 7.70 ± 0.11% (60.7 ± 1.2 mmol/mol) to 7.57 ± 0.11% (59.6 ± 1.3 mmol/mol); intergroup difference in change -0.07 [95% CI -0.31, 0.18]. Waist circumference decreased more in INT than CON after six months (p = 0.02). Muscular strength increased more in INT than in CON (p 0.001). There were no intergroup differences in hypoglycemia or any other variables.Adding resistance training did not impact glycemia, but it increased strength and reduced waist circumference, in aerobically active individuals with type 1 diabetes.

BACKGROUND The Carpentier-Edwards Perimount valves have a proven track record in aortic valve replacement: good durability, hemodynamic performance, rates of survival, and low rates of valve-related complications and prosthesis-patient mismatch. The St. Jude Medical Trifecta is a newer valve that has shown comparable early and midterm outcomes. Studies show reoperation rates of Trifecta are comparable with Perimount valves, with a few recent studies bringing into focus early structural valve deterioration (SVD), and increased midterm SVD in younger patients. Given that midterm data for Trifecta is still sparse, we wanted to confirm the early low reoperation rates of Trifecta persist over time compared with Perimount. METHODS The Maritime Heart Centre Database was searched for AVR between 2011 and 2016, inclusive. The primary endpoint of the study was all-cause reoperation rate. RESULTS In total, 711 Perimount and 453 Trifecta implantations were included. The reoperation hazards were determined for age: 0.96 (0.92-0.99; p = .02), female (vs. male): 0.35 (0.08-1.53; p = .16), smoker (vs. nonsmoker): 2.44 (0.85-7.02; p = .1), and Trifecta (vs. Perimount): 2.68 (0.97-7.39; p = .06). Kaplan-Meier survival analysis in subgroups-age

Patients with sellar masses (SM) frequently have secondary hormonal deficiency (SHD) at initial presentation. While larger SM are more likely to present with SHD, it is unclear whether SHD at presentation is influenced by the type of SM.We conducted a retrospective analysis of patients with SM prospectively enrolled in our comprehensive provincial neuropituitary registry between November 2005 and December 2018. SM were subdivided based on size: 1 cm, 1-1.9 cm, 2-2.9 cm, and 3 cm.A total of 914 patients met the inclusion criteria, including: 346 nonfunctioning adenomas (NFA), 261 prolactinomas (PRLoma), 51 growth hormone adenomas, 36 adrenocorticotropic adenomas, 93 Rathke's cleft cysts, 70 craniopharyngiomas and 57 meningiomas. The overall rate of SHD at presentation was highest in PRLoma (62.8%) and craniopharyngiomas (64.3%) and lowest in meningiomas (14%). While larger SM were significantly more likely to have SHD, the rate of SHD within each group was significantly different despite similar size (p 0.001). Of the two largest groups of SM (NFA and PRLoma), NFA had significantly higher odds ratio (3.34, CI 1.89-5.89) of having multiple SHDs when compare with PRLoma, even when corrected for age, gender and size of tumor (p 0.001).Our study shows that the rate and distribution of SHD in SM vary dependent upon the size of the tumor and specific pathology; in particular, NFA are more likely to present with multiple SHDs. Our data will help clinicians in determining adequate hormonal testing strategy for different SM.

The aim of this study was to test the hypotheses that, during manual-wheelchair foot propulsion backward on a soft surface, lowering the seat height increases speed, push frequency and push effectiveness, and decreases perceived difficulty.In a repeated-measures crossover study, 50 able-bodied participants used one foot to propel a manual wheelchair 5 m backward on a soft surface at 5 seat heights, ranging from 5.08 cm below to about 5.08 cm above lower-leg length, in random order. We recorded Wheelchair Skills Test (WST) capacity scores and used the Wheelchair Propulsion Test (WPT) to calculate speed (m/s), push frequency (cycles/s) and push effectiveness (m/cycle). We also recorded the participants' perceived difficulty (0-4) and video-recorded each trial.WST capacity scores were reduced at the higher seat heights. Using repeated-measures models (adjusted for age, sex and order), there were negative relationships between seat height and speed (During manual-wheelchair foot propulsion backward on a soft surface, lowering the seat height increases speed and push effectiveness, and decreases perceived difficulty.IMPLICATIONS FOR REHABILITATIONBackward wheelchair foot propulsion on soft surfaces is affected by seat height.Speed (m/s) is improved if the seat height is lowered.Push effectiveness (m/gait cycle) is improved if the seat height is lowered.Perceived difficulty of propulsion is lower if the seat height is lowered.

The study's objective was to examine Canadian and Australian community pharmacists' experiences with people at risk of suicide.A survey was developed and administered online. Countries were compared by Fisher's exact and t tests. Multivariable logistic-regression analysis was used to identify variables associated with preparedness to help someone in a suicidal crisis.The survey was completed by 235 Canadian and 161 Australian pharmacists. Most (85%) interacted with someone at risk of suicide at least once, and 66% experienced voluntary patient disclosure of suicidal thoughts. More Australians than Canadians had mental health crisis training (p0.001). Preparedness to help in a suicidal crisis was negatively associated with being Canadian, having a patient who died by suicide, lacking training and confidence, and permissive attitudes toward suicide.Several perceived barriers impede pharmacists' abilities to help patients who voluntarily disclose suicidal thoughts. Gatekeeper and related suicide prevention strategy training for community pharmacists is warranted.

This study investigated the impact of exercise training on interindividual variability and response rates in body composition and cardiometabolic outcomes in adolescents with obesity. Postpubertal males and females (n = 143) were randomly assigned to 6 months of a diet-only control or aerobic, resistance, or combined exercise training. Body composition indices were percentages of body fat mass and lean body mass and waist circumference. Biomarkers of cardiometabolic health were systolic blood pressure and plasma fasting glucose, triglycerides, and high-density lipoprotein cholesterol. Interindividual variability was examined by comparing the standard deviation of individual responses (SDIR) to a smallest robust change (SRC). The typical error of measurement was used to classify responses. SDIR exceeded the SRC for percent body fat mass in all exercise groups (SRC = 1.04%; aerobic SDIR = 1.50%; resistance SDIR = 1.22%; combined SDIR = 2.29%), percent lean body mass (SRC = 1.38%; SDIR = 3.2%,), systolic blood pressure (SRC = 2.06 mm Hg; SDIR = 4.92 mm Hg) in the resistance group, and waist circumference (SRC = 2.33 cm; SDIR = 4.09 cm), and fasting glucose (SRC = 0.08 mmol/L; SDIR = 0.28 mmol/L) in the combined group. However, half of the reported variables (11/21) did not have a positive SDIR. Importantly, adverse response rates were significantly lower in all 3 exercise groups compared with control for body composition. Although exercise had a small influence on interindividual variability for indices of body composition, the rate of adverse responses did not increase for any outcome. Novelty Interindividual variability and individual responses to exercise training have not been investigated in adolescents with obesity. Six months of exercise training does not increase interindividual variability in adolescents with obesity. Exercise created a positive, uniform shift in responses.

Vasovagal syncope (VVS) occurs in40% of individuals at least once in their lifetime. Sex-dependent differences in presentation and outcomes are not understood. We sought to determine differences in clinical presentation, treatment modalities, and outcomes of VVS between men and women.Data were collected as part of the Prevention of Syncope Trials (POST) I and II, 2 multicenter, placebo-controlled, randomized trials testing the effectiveness of metoprolol and fludrocortisone, respectively. Data regarding clinical presentation, outcomes, and time to first syncope event after randomization were compared.Of the 418 patients (280 women and 138 men), women were younger at the time of first syncope event (21 vs 26 years P = 0.002) and had a lower baseline systolic blood pressure (117 vs 124 mm Hg, P0.001). Response to heat as a trigger for syncope was more common in women (68% vs 48%, P = 0.011). Clinical presentation in women consisted more commonly of feeling warm, having seizures, and experiencing more postsyncope fatigue (68% vs 54%, P = 0.048; 10% vs 2.7%, P = 0.045; 75% vs 59%, P = 0.017, respectively). Women were more likely to experience recurrent syncope after adjustment for prerandomization syncope burden and randomization assignment (hazard ratio, 1.56; 95% confidence interval, 1.10-2.22; P = 0.012).Clinical presentation and provocative factors of VVS differ between men and women, as do recurrent events. Recognition of these differences may help target therapy specifically in men and women.

Aims Catheter ablation is superior to escalated antiarrhythmic drugs among patients with ventricular tachycardia (VT) and prior myocardial infarction (MI). However, it is uncertain whether clinical VT characteristics, should influence choice of therapy. The purpose of this study was to evaluate whether presentation with electrical storm and the clinical VT cycle length predicted response to ablation vs. escalated antiarrhythmic therapy. Methods and results All patients enrolled in the Ventricular Tachycardia Ablation vs. Escalated Antiarrhythmic Drug Therapy in Ischaemic Heart Disease (VANISH) trial were included. The association between VT cycle length and presentation with electrical storm and the primary outcome of death, subsequent VT storm or appropriate ICD shock was evaluated. Among the study population of 259 patients, escalated antiarrhythmic drug therapy had worse outcomes for those presenting with a VT cycle length >400 ms [ Conclusion The VT cycle length can influence response to either ablation or escalated drug therapy in patients with VT and prior MI. Those with slow VT had improved outcomes with ablation. Patients presenting with electrical storm demonstrated similar outcomes to the overall trial population, with a trend to benefit of catheter ablation, particularly in those on amiodarone.

We examined the characteristics and outcomes in a contemporary ambulatory population of patients with atrial fibrillation (AF), comparing rate control with rhythm control.This is a post hoc analysis of a cluster-randomized trial (A total of 870 patients were included in this analysis, 99 (11.4%) in the rhythm-control group, and 40% women. In the rhythm-control group, the mean age was younger (70 ± 11.4 vs 72.7 ± 9.5 years,Both rate- and rhythm-control patients have recurrent ED visits, with a higher rate in patients treated with rhythm control. These findings are observational, but taken in the context of current guidelines could help develop further therapies aimed at improving symptom burden in both rhythm- and rate-control patients to broadly improve healthcare utilization in the AF population.Nous avons examiné les caractéristiques et le devenir de patients ambulatoires contemporains atteints de fibrillation auriculaire (FA) dans le cadre d’une comparaison entre la maîtrise de la fréquence cardiaque et la maîtrise du rythme cardiaque.Nous avons effectué une analyseAu total, 870 patients ont été inclus dans cette analyse; 99 (11,4 %) faisaient partie du groupe pris en charge par une maîtrise du rythme cardiaque, et 40 % étaient de femmes. Dans le groupe pris en charge par une maîtrise du rythme cardiaque, l’âge moyen était moindre (70 ± 11,4 ans vs 72,7 ± 9,5 ans,Des consultations répétées aux urgences ont été notées tant chez les patients pris en charge par une maîtrise de la fréquence cardiaque que chez ceux pris en charge par une maîtrise du rythme cardiaque quoique plus fréquemment chez ces derniers. Nos constats sont de type observationnel. Néanmoins, dans le contexte des lignes directrices actuelles, ils pourraient contribuer à la mise au point d’autres traitements visant à atténuer le fardeau des symptômes tant chez les patients pris en charge par une maîtrise du rythme cardiaque que chez ceux pris en charge par une maîtrise de la fréquence cardiaque et ainsi permettre globalement une meilleure utilisation des soins de santé chez les patients atteints de FA.

We previously studied the genetic and immunohistochemical profiles of subsets of Merkel cell carcinoma (MCC) stratified by morphology and Merkel cell polyomavirus (MCPyV) status. Recent advances in the immunotherapy of this disease prompted us to examine markers of immunogenicity [PD-L1 expression and tumor-infiltrating lymphocytes (TILS) in these subsets]. The observed clinical responses to checkpoint inhibition of the PD-1/PD-L1 pathway have not correlated with PD-L1 expression by MCC cells, and recent evidence suggests that functions of this pathway within the immune tumor microenvironment may be relevant. We conducted a semiquantitative (high, moderate, and minimal) immunohistochemical evaluation of the global PD-L1 signal in 52 cases of MCC, segregated in 3 subsets [pure MCPyV-positive (n = 28), pure MCPyV-negative (n = 9), and combined MCPyV-negative (n = 15)]. TILS were categorized as brisk, nonbrisk, or absent. Intersubset comparisons revealed that high global PD-L1 signals were exclusively associated with pure MCPyV-positive MCCs contrasted with virus-negative cases (P = 0.0003). Moderate signals were seen across all 3 groups. Brisk TILS were significantly associated with MCPyV-positive MCCs compared with MCPyV-negative cases (P = 0.029). Neither parameter (PD-L1 or TILS) was significantly different between the MCPyV-negative groups. Of potential clinical relevance, MCPyV seems to convey greater immunogenicity to MCCs than the high mutational burden/greater neoantigen load of MCPyV-negative cases. Interesting too is the fact that subset-related profiles of these markers mirrored those noted at genetic and immunohistochemical levels, separating pure MCPyV-positive MCCs from the virus-negative subsets.

Summary Introduction Despite efforts to improve adherence to physical activity interventions in youth with obesity, low adherence and attrition remain areas of great concern. Objective The study was designed to determine which physiological and/or psychological factors predicted low adherence in adolescents with obesity enrolled in a 6‐month exercise intervention study aimed to improve body composition. Methods Three hundred four adolescents with obesity aged 14–18 years who volunteered for the HEARTY (Healthy Eating Aerobic and Resistance Training in Youth) randomized controlled trial completed physiological (body mass index, waist circumference, per cent body fat, resting metabolic rate and aerobic fitness) and psychological (body image, mood, self‐esteem and self‐efficacy) measures. Results One hundred forty‐one out of 228 (62%) randomized to exercise groups had low adherence (completed

BACKGROUND Phlebotomy for diagnostic testing is among the commonest hospital procedures, but hospital-wide surveys of all inpatients characterizing blood draw volumes have not been published. The objectives were to characterize the daily blood volumes drawn for diagnostic testing from patients discharged from a Canadian tertiary care center, describe the daily distributions of phlebotomy volumes across service locations, and describe changes in hemoglobin (Hb) and transfusion across service locations. STUDY DESIGN AND METHODS Data were obtained on all patients discharged between 2012 and 2014 using linked discharge abstract and laboratory data. Cumulative daily blood volume and draw frequency were reported by service and days since admission. Changes in Hb and red blood cell (RBC) transfusion rates were reported for nontransfused and transfused patients. RESULTS Data were included on 59,715 subjects. Mean daily estimated blood loss varied from 8.5 ± 6.5 mL/day onward to 27.2 ± 20.0 mL/day in the intensive care unit (ICU; p

Background: Prior studies have demonstrated an association between appropriate implantable cardioverter defibrillator (ICD) shocks and mortality in clinical trials. The effect of shock burden on heart failure and mortality has not been previously studied in a large population-based cohort. Methods: The cohort was derived using a comprehensive prospective ICD registry in the province of Nova Scotia with a mean follow-up of 4 ± 2.3 years. With the use of time-varying analysis, the relationship among shock burden, mortality, and heart failure hospitalization was determined. Results: A total of 776 patients (mean age of 64.8 years) were included in the study, of whom 37% received appropriate therapy during follow-up. A single ICD shock did not confer an increased mortality risk compared with no therapy (hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.84-1.79; P = 0.3), but mortality risk was significantly increased with ≥ 2 shocks (HR, 3.23; 95% CI, 2.04-5.09; P < 0.0001). There was a significant increase in heart failure hospitalization associated with receiving 1 ICD shock (HR, 2.05; 95% CI, 1.46-2.89; P < 0.0001) or more than 1 ICD shock (HR, 4.36; CI, 2.53-7.52; P < 0.0001) compared with patients receiving no ICD therapy. Patients who received antitachycardia pacing alone showed no difference in heart failure hospitalization (HR, 0.93; CI, 0.67-1.29; P = 0.7) and improved survival (HR, 0.69; CI, 0.5-0.96; P = 0.03) compared with those receiving no ICD therapy. Conclusion: Ventricular arrhythmia treated with appropriate ICD shocks is associated with an increased risk of heart failure hospitalization, whereas recurrent episodes of ventricular arrhythmia requiring shocks are associated with both higher mortality and higher heart failure hospitalization rates. Résumé: Contexte: Des études menées antérieurement ont révélé l’existence d’un lien entre l’administration appropriée de décharges électriques au moyen d’un défibrillateur cardioverteur implantable (DCI) et la mortalité au cours des essais cliniques. L’effet de telles décharges sur l’insuffisance cardiaque et la mortalité n’avait encore jamais été étudié au sein d’une cohorte d’envergure représentative de la population. Méthodologie: La cohorte a été établie au moyen d’un registre prospectif exhaustif des DCI implantés chez des patients de la Nouvelle-Écosse ayant fait l’objet d’un suivi moyen de 4 ± 2,3 ans. La relation entre le fardeau imposé par les décharges, la mortalité et l’hospitalisation pour insuffisance cardiaque a été déterminée au moyen d’une analyse en fonction du temps. Résultats: Au total, 776 patients (âge moyen : 64,8 ans) ont été admis dans l’étude; 37 % d’entre eux avaient reçu un traitement approprié au cours de la période de suivi. Une seule décharge délivrée par un DCI n’augmentait pas le risque de mortalité par rapport à l’absence de traitement (rapport des risques instantanés [RRI] de 1,23; intervalle de confiance [IC] à 95 %, de 0,84 à 1,79; p = 0,3), mais le risque de mortalité était significativement accru chez les patients ayant reçu ≥ 2 décharges (RRI de 3,23; IC à 95 %, de 2,04 à 5,09; p < 0,0001). Le risque d’hospitalisation pour insuffisance cardiaque s’est révélé significativement supérieur chez les sujets ayant reçu 1 décharge par DCI (RRI de 2,05; IC à 95 %, de 1,46 à 2,89; p < 0,0001) ou plus de 1 décharge par DCI (RRI de 4,36; IC à 95 %, de 2,53-7,52; p < 0,0001), comparativement à ceux n’ayant reçu aucun traitement par DCI. On n’a observé aucune différence quant à l’hospitalisation pour insuffisance cardiaque (RRI de 0,93; IC à 95 %, de 0,67 à 1,29; p = 0,7) et à l’amélioration de la survie (RRI de 0,69; IC à 95 %, de 0,5 à 0,96; p = 0,03) chez les patients qui ont reçu uniquement une stimulation antitachycardie comparativement à ceux qui n’ont reçu aucun traitement par DCI. Conclusion: L’arythmie ventriculaire traitée de façon appropriée au moyen de décharges électriques délivrées par un DCI est associée à un risque accru d’hospitalisation pour insuffisance cardiaque, tandis que des épisodes récurrents d’arythmie ventriculaire exigeant un traitement par décharge électrique sont associés à des taux supérieurs de mortalité et d’hospitalisation pour insuffisance cardiaque.

The literature records many examples of Merkel cell carcinoma (MCC) exhibiting aberrant immunohistochemical profiles. These can lead to diagnostic difficulty. The objectives of the current study were (1) to examine the immunohistochemical profile of different subsets of MCC to determine whether predictable subset-specific patterns exist and (2) to establish whether shared immunophenotypic patterns might reveal links between individual subsets, as demonstrated previously at a genetic level. In 52 cases of MCC, stratified by viral status and morphology, we studied 5 markers commonly used in the diagnostic evaluation of these tumors (CK20, CK7, chromogranin, neurofilament and TTF-1). Expression of these proteins was recorded as quantitative (H-scores) and absolute (positive vs negative) variables. In general, our data indicate that the "classical" or expected panel (CK20+, NF+, Chromo+, TTF-1, CK7-) is observed significantly more often in pure Merkel cell polyomavirus (MCPyV)-positive than in MCPyV-negative cases (78% vs 25%; P = .002). Neurofilament was less frequently encountered in MCPyV-negative than in MCPyV-positive tumors (66.7% vs 100%; P = .001) and expression of TTF-1 (37.5% vs 3.6%; P = .003) and CK7 (45.8 vs 14.3; P = .02) was more frequent. No significant immonophenotypic differences were observed between pure and combined MCPyV-negative tumors. Recognition of the more aberrant immunohistochemical profile of MCPyV-negative MCC should inform the diagnostic approach to this tumor. Moreover, the shared aberrant immunophenotype in pure and combined MCPyV-negative tumors supports a link between these entities and serves to separate them from MCPyV-positive tumors.

Background Comparisons between frailty assessment tools for waitlist candidates are a recognized priority area for kidney transplantation. We compared the prevalence of frailty using three established tools in a cohort of waitlist candidates. Methods Waitlist candidates were prospectively enrolled from 2016 to 2020 across five centers. Frailty was measured using the Frailty Phenotype (FP), a 37-variable frailty index (FI), and the Clinical Frailty Scale (CFS). The FI and CFS were dichotomized using established cutoffs. Agreement was compared using κ coefficients. Area under the receiver operating characteristic (ROC) curves were generated to compare the FI and CFS (treated as continuous measures) with the FP. Unadjusted associations between each frailty measure and time to death or waitlist withdrawal were determined using an unadjusted Cox proportional hazards model. Results Of 542 enrolled patients, 64% were male, 80% were White, and the mean age was 54±14 years. The prevalence of frailty by the FP was 16%. The mean FI score was 0.23±0.14, and the prevalence of frailty was 38% (score of ≥0.25). The median CFS score was three (IQR, 2–3), and the prevalence was 15% (score of ≥4). The κ values comparing the FP with the FI (0.44) and CFS (0.27) showed fair to moderate agreement. The area under the ROC curves for the FP and FI/CFS were 0.86 (good) and 0.69 (poor), respectively. Frailty by the CFS (HR, 2.10; 95% CI, 1.04 to 4.24) and FI (HR, 1.79; 95% CI, 1.00 to 3.21) was associated with death or permanent withdrawal. The association between frailty by the FP and death/withdrawal was not statistically significant (HR, 1.78; 95% CI, 0.79 to 3.71). Conclusion Frailty prevalence varies by the measurement tool used, and agreement between these measurements is fair to moderate. This has implications for determining the optimal frailty screening tool for use in those being evaluated for kidney transplant.

Background The genetics of binge-eating disorder (BED) is an emerging topic, with dopaminergic genes being implicated in its etiology due to the role that dopamine (DA) plays in food reward sensitivity and self-regulation of eating behavior. However, no study to date has examined if DA genes influence response to behavioral treatment of BED. Objective The primary objective of this study was to examine the ability of DA-associated polymorphisms to predict BED treatment response measured using binge frequency over 12 months. As secondary objectives, this study examined cross-sectional relationships between these polymorphisms and anthropometrics in women living with and without BED and obesity. Methods Women aged 18–64 years old were genotyped for the DA-related SNPs DRD2/ANKK1 Taq1A (rs1800497) and COMT (rs4680), as well as the DA-related uVNTRs DAT-1 (SLC6A3) and MAO-A. A multi-locus DA composite score was formed from these 4 polymorphisms using genotypes known to have a functional impact resulting in modified DA signaling. Binge frequency (Eating Disorder Examination – Interview) and body composition (Tanita BC-418) were assessed in a pre-post analysis to examine genetic predictors of treatment response in women living with obesity and BED. Secondary data analysis was conducted on a cross-sectional comparison of three groups of women enrolled in trial group treatment for BED: women living with obesity and BED (n = 72), obesity without BED (n = 27), and normal-weight without BED (n = 45). Results There were no significant genotype × time interactions related to anthropometrics or binge frequency for any individual DA genotypes, or to the composite score reflecting DA availability. At baseline, there were no significant between-group differences in frequencies of DA-related alleles, nor were there associations between genotypes and anthropometrics. Conclusions Our study found no evidence to suggest that the DRD2/ANKK1 Taq1A, COMT, MAO-A, or DAT-1 polymorphisms are associated with response to behavioral intervention for BED as measured by changes in binge frequency. Future studies should examine a greater variety of dopaminergic polymorphisms, other candidate genes that target other neurotransmitter systems, as well as examine their impact on both behavioral and pharmacological-based treatment for BED.

Background: Remote monitoring is used to supplement in-clinic follow-up for patients with cardiac implantable electronic devices (CIEDs) every 6-12 months. There is a need to optimize remote management for CIEDs because of the consistent increases in CIED implants over the past decade. The objective of this study was to investigate real and perceived barriers to the use of remote patient management strategies in Canada and to better understand how remote models of care can be optimized. Methods: We surveyed 512 CIED patients and practitioners in 22 device clinics in Canada. Results: Device clinic surveys highlighted significant variation and inconsistency in follow-up care for in-clinic and remote visits across and within clinics. This survey showed that funding policies and management of additional workflow are barriers to optimal use and uptake. Despite this, device clinics perceive remote follow-up as a valuable resource and an efficient way to manage patient follow-up. Patients were broadly satisfied with their CIED follow-up care but identified barriers related to coordination of care, visit logistics, and information needs. Views varied as a function of clinical or sociodemographic characteristics. Most patients (n = 228; 91%) expressed a desire to receive a phone call from their device clinic after a remote transmission has been received. Conclusions: Lack of a unified, guideline-supported approach to follow-up after CIED implant, and discrepant funding policies across jurisdictions, are significant barriers to the use of remote patient management strategies in Canada. Efforts to increase or expand use of remote follow-up must recognize these barriers and the needs of specific subgroups of patients. Résumé: Introduction: La télésurveillance sert de complément à la consultation en clinique des patients porteurs d’un dispositif cardiaque électronique implantable (DCEI) tous les 6 à 12 mois. Il est nécessaire d’optimiser la prise en charge à distance des patients porteurs de DCEI en raison de la constante augmentation des implantations de DCEI au cours de la dernière décennie. L’objectif de la présente étude était d’examiner les obstacles réels et perçus à l’utilisation des stratégies de prise en charge à distance des patients du Canada et de mieux comprendre la façon d’optimiser les modèles de soins à distance. Méthodes: Nous avons interrogé 512 patients porteurs de DCEI et praticiens de 22 cliniques spécialisées en DCEI du Canada. Résultats: Les enquêtes des cliniques spécialisées en DCEI ont fait ressortir la variation importante et le manque d’uniformité dans les soins de suivi lors des consultations en clinique et à distance au sein de toutes les cliniques et entre elles. Cette enquête a montré que les politiques de financement et la gestion du flux de travail supplémentaire sont les obstacles qui empêchent l’utilisation optimale et l’adoption. Malgré cela, les cliniques spécialisées en DCEI perçoivent le suivi à distance comme une ressource très utile et un moyen efficace de prendre en charge le suivi du patient. Les patients étaient dans l’ensemble satisfaits de leurs soins de suivi relatifs à leur DCEI, mais relevaient des obstacles liés à la coordination des soins, à la logistique des consultations et à leurs besoins d’information. Les points de vue variaient en fonction des caractéristiques cliniques et sociodémographiques. La plupart des patients (n = 228 ; 91 %) ont fait part de leur souhait de recevoir un appel téléphonique de leur clinique spécialisée en DCEI après la réception de la transmission à distance. Conclusions: L’absence d’une approche unifiée et fondée sur les lignes directrices qui porte sur le suivi après l’implantation de DCEI, et la divergence des politiques de financement des provinces et territoires sont des obstacles importants à l’utilisation de stratégies de prise en charge à distance des patients au Canada. Les efforts visant à accroître ou à étendre l’utilisation du suivi à distance doivent tenir compte de ces obstacles et des besoins des sous-groupes particuliers de patients.

Objective: To determine the predictors of postoperative AKI following non-emergent cardiac surgery among patients with variable preoperative eGFR levels. Methods: Retrospective study of patients who underwent elective or in-hospital cardiac surgical procedures performed between January 2006 and November 2015. The procedures included isolated CABG, isolated AVR or combined CABG and AVR. The primary outcome AKI (any stage) following non-emergent cardiac surgery utilizing the 2012 KDIGO criteria. Patients were categorized based the following renal outcomes: mild AKI, severe AKI (KDIGO stage 2 or 3) and post-operative dialysis.. Results: A total of 6713 patients were included in our study. The mean age was 66.8 years (SD ± 10.3), with 76.2% being males. A total of 4487 patients had normal or mildly decreased eGFR (G1 or G2) preoperatively (66.8%), while 1960 patients were in the G3 category (29.1%). Only 266 patients (3.9%) had G4 or worse renal function. A total of 1489 (28.5%) patients experienced post-operative AKI. The need for postoperative dialysis occurred in 4.2% of the AKI subgroup. In-hospital mortality was higher among the AKI subgroup (7.3% vs 0.5%, p

INTRODUCTION: With the shift to competency-based training, surgical skills lab training (SSLT) may become a mandatory part of Canadian urology residency programs (CURPs). This study aims to identify: 1) the status of SSLT in CURP; 2) stakeholder perspectives on the utility of SSLT; 3) barriers to developing and implementing SSLT; and 4) how to address these barriers. METHODS: Surveys were developed and issued to three groups of stakeholders: 1) SSLT directors at all 13 CURPs (response rate 100%); 2) teaching faculty (response rate 33%); and 3) urology residents (response rate 24%). Surveys 2 and 3 were sent to 10 English CURPs. Results were collected through email and SurveyMonkey(®). RESULTS: Nine of 13 CURPs have a dedicated SSLT; 46% of CURP have 1–3 sessions per year, 8% have 5–7, and 30% >7. Most residents have independent lab access, but 80% do so less than once monthly. Over 90% of stakeholders find SSLT useful, of which high-fidelity models are most preferred (faculty rated 3.66/4, residents 3.18/4). Program directors (PDs) identified lack of protected faculty time, funding, and infrastructure as the top three barriers to SSLT implementation. Residents found lack of faculty time, protected academic time, and infrastructure as barriers. PDs viewed protecting faculty time and more funding as potential solutions, while residents suggested protected faculty and academic time, and after-hours lab access. CONCLUSIONS: Residents, faculty, and PDs in CURPs view SSLT as useful. Most CURPs have defined SSLT; programs without this have labs for resident use but are underused. To continue to develop and progress SSLT, more time, participation, and funding must be made available.

Purpose: To determine the extent to which Occupational Therapists (OTs) in Nova Scotia (NS) conduct wheelchair skills training, the nature of training and the OTs’ perceptions on training. Materials and methods: Anonymous online survey. Results: We received 110 responses from OTs living in NS and involved in direct patient care, 96 (93%) of whom reported helping clients obtain manual wheelchairs. Of the OTs who responded to the question “…do you typically provide wheelchair-skills training…?”, 40 (43.5%) answered “Yes, usually” for clients and 40 (46.0%) for caregivers. The median duration of training sessions for clients and caregivers was 30 and 20 min; the median number of sessions was 2 and 1. Regarding the importance of training, 65 (73.9%) OTs answered “Very important” and 22 (25%) “Somewhat important” for clients and 55 (64.0%) answered “Very important” and 29 (33.7%) “Somewhat important” for caregivers. About one-third of OTs considered themselves adequately prepared for the trainer role. A variety of barriers and facilitators to training were identified. Trainers were significantly more likely than non-trainers to consider wheelchair skills training as important (p = .0003 for clients and p = .0039 for caregivers) and to consider themselves adequately prepared for the trainer role (p = .002 for clients and .003 for caregivers). Conclusions: Only a minority of NS OTs usually provide wheelchair-skills training for clients or their caregivers and the training provided is minimal, despite a majority who consider such training to be important. Only about one-third of OTs feel prepared for the training role.Implications for rehabilitationOnly a minority of Occupational Therapists (OTs) in Nova Scotia, Canada usually provide wheelchair-skills training for clients or their caregivers.The training that is provided is minimal.A majority of OTs consider such training to be important.Only about one-third of OTs feel prepared for the training role. Only a minority of Occupational Therapists (OTs) in Nova Scotia, Canada usually provide wheelchair-skills training for clients or their caregivers. The training that is provided is minimal. A majority of OTs consider such training to be important. Only about one-third of OTs feel prepared for the training role.

Exercise may improve cardiometabolic, reproductive and psychological outcomes in women with Polycystic Ovary Syndrome (PCOS). Clinical Practice Guidelines recommend exercise to treat PCOS, but the most effective exercise prescription is unclear. The aim of this randomized controlled trial was to evaluate the effects of six months of thrice weekly high-intensity interval training (HIIT) and continuous aerobic exercise training (CAET) programs compared with no exercise in previously-inactive women aged 18–40 years with PCOS. The primary outcome was change in ovulation rate. Ovulation was assessed with daily at home ovulation prediction kits, and confirmed with serum progesterone levels. Fisher’s exact test was used to compare groups. Secondary outcomes included change in BMI, waist circumference, blood pressure, A1C, fasting glucose, fasting insulin, and lipids and were analyzed using repeated measures mixed models. 47 women were randomly assigned to no exercise control (n=17), HIIT (n=16), or CAET (n=14). 22/33 (66.7%) women ovulated during the intervention period: no exercise: 8/12 (66.7%), HIIT: 8/11 (72.7%), and CAET: 6/10 (60%); NS between groups. BMI decreased significantly in the CAET group compared with control (-1 kg/m2, p=0.01) and compared with HIIT (-0.9 kg/m2, p=0.04). Mean waist circumference decreased significantly in all groups with no significant difference between groups. There were no significant within- or between- group changes for body weight. No within- or between group differences were identified for mean blood pressure, A1C, fasting glucose, fasting insulin, or triglycerides. Mean LDL-C was significantly different between the HIIT and CAET groups (-0.33 mmol/L, p=0.03), as LDL-C decreased in the HIIT group but not in the CAET group. HDL-C increased in the HIIT group compared with the no exercise group (0.18 mmol/L, p=0.04), with no significant difference between the CAET and no exercise groups (p=0.47). In conclusion, CAET and HIIT interventions in women with PCOS did not affect ovulation rates. CAET and HIIT both were effective at improving anthropometrics and some cardiometabolic health markers in women with PCOS. Further studies are needed to determine optimal exercise prescriptions for reproductive, anthropometric and cardiometabolic outcomes in women with PCOS.

Introduction The Diabetes Aerobic and Resistance Exercise trial found that aerobic training and resistance training alone each reduced hemoglobin A1c (HbA1c) compared with nonexercising controls, and combined aerobic and resistance training caused greater HbA1c reduction than either training type alone. Our objective was to determine whether a dose-response relationship existed between frequency of exercise training and HbA1c change, and whether this varied by exercise modality or participant characteristics. Methods Post hoc analysis of data from 185 Diabetes Aerobic and Resistance Exercise trial participants with type 2 diabetes randomized to aerobic, resistance or combined training thrice weekly. Dose-response relationships between adherence (percent of prescribed training sessions completed) and HbA1c change were assessed with linear regression. Results Median overall adherence was 84.9% (interquartile range, 74.4%-93.6%). Higher exercise adherence was associated with greater HbA1c reduction; a 20% increase in adherence (e.g., an additional two sessions per month) was associated with a 0.15% (2 mmol·mol) decrease in HbA1c (β = -0.0076, R = -0.170, P = 0.021). Significant dose-response relationships were identified for aerobic (β = -0.0142, R = -0.313, P = 0.016) and combined training (β = -0.0109, R = -0.259, P = 0.041), but not resistance training (β = 0.0068, R = 0.153, P = 0.233). Dose-response relationships in all training groups combined were significant in subgroups younger than 55 yr (β = -0.0113, R = -0.286, P = 0.005), males (β = -0.0123, R = -0.234, P = 0.010), and baseline HbA1c ≥7.5% (58 mmol·mol) (β = -0.013, R = -0.263, P = 0.011). Conclusions There was a dose-response relationship between adherence to prescribed exercise and HbA1c reduction suggesting that glycemic control is improved more in individuals with type 2 diabetes with a higher training volume. Dose-response relationships existed for aerobic and combined training but not resistance training. These findings support aerobic and combined exercise prescriptions outlined in clinical practice guidelines.

Introduction: Certain adult conditions treated by paramedics, such as myocardial infarction or stroke, have better outcomes if transported to a specialty centre, bypassing local generalist facilities when necessary. Little evidence exists to inform guidelines to identify pediatric patients who would benefit from direct transport to a pediatric centre. This study describes the characteristics of children brought to community emergency departments (ED) who subsequently required transfer to pediatric specialty care. Methods: A retrospective observational cohort study was performed in a metropolitan area with one tertiary pediatric specialty centre and four community EDs. The patient care record database was queried for patients under 16 years old transported by paramedics to a community ED during a five-year period. Secondary transfer to the pediatric specialty centre within 24 hours was identified. The primary outcome was percentage of transfers to specialty care. Descriptive statistics were used to characterize the whole group as well as stratified by age category, chief complaint and Canadian Triage Acuity Scale (CTAS). Results: A total of 872 pediatric patients were transported to community EDs with 95 (10.9%) requiring secondary transfer to the pediatric specialty centre. CTAS 1 and 2 were associated with increased secondary transfer (p

The literature suggests that p63 expression in Merkel cell carcinoma (MCC) is associated with a poor prognosis. p63 immunohistochemistry marks the 2 main isoforms of this transcriptional protein: TAp63 (tumor suppressor-like properties) and ∆Np63 (oncogenic properties). Little information about the isoform of relevance in MCC exists. p40 immunohistochemistry specifically marks ∆Np63, and using comparative, semiquantitative expression of p63 and p40, we sought to clarify the issue. Our cohort of 53 cases (28 men and 25 women, median age 79 years, interquartile range 71-88) was stratified by morphology and viral status. Immunohistochemistry (p63, p40, and cytokeratin 5/6) was performed, H-scores for nuclear expression of p63 and p40 were derived (2 observers; positivity ≥ 10), and interobserver agreement was evaluated. Clinical, pathological, and outcome data were documented. The results were analyzed statistically. Mortality amounted to 57% (median follow-up 686 days, interquartile range 292-1599). Positivity for Merkel cell polyomavirus was observed in 29 (55%) of cases. Expression of p63 and p40 was present in 36 (69%) and 4 (8%) of cases, respectively. Increased age (P = .0241), negative Merkel cell polyomavirus status (P = .0185), and p63 positivity (P = .0012) were significantly associated with mortality. The latter 2 variables were highly correlated (P = .004). The interclass correlation between the 2 sets of H-scores was 0.95. Our findings support an association between p63 expression and reduced overall survival in MCC and show consistency in scoring this prognostic parameter. TAp63 is the dominant isoform of the protein involved. The paradoxical tumor suppressor-like activity of this isoform in p63-positive MCCs with reduced overall survival requires further study.

Background The combined effect of a low-carbohydrate, high-protein (LCHP) diet and omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation on patients with type 2 diabetes (T2D) is not known. Objective The aim of this study was to evaluate the effect of an LCHP diet combined with ω-3 (LCHP+ω-3) on glycemic control in patients with T2D. Design In this randomized, double-blind, parallel-controlled trial, 122 newly diagnosed participants with T2D were randomly assigned to receive a high-carbohydrate, low-protein diet with low ω-3 PUFAs [control (CON)], an LCHP, ω-3, or LCHP+ω-3 diet for 12 wk. The ratio of carbohydrate to protein was 42:28 in the LCHP and LCHP+ω-3 diet and 54:17 in the CON and ω-3 diet. The participants were given 6 g fish oil/d (containing 3.65 g docosahexaenoic acid, eicosapentaenoic acid, and docosapentaenoic acid/d) in the ω-3 and LCHP+ω-3 diet groups or 6 g corn oil/d (placebo) in the CON and LCHP diet groups. Results Compared with the CON diet group, greater decreases in glycated hemoglobin (HbA1c) and fasting glucose were observed in all of the other 3 diet groups at 12 wk. Of note, HbA1c reduction in the LCHP+ω-3 diet group (-0.51%; 95% CI: -0.64%, -0.37%) was greater than that in the LCHP (P = 0.03) and ω-3 (P = 0.01) diet groups at 12 wk. In terms of fasting glucose, only the LCHP+ω-3 diet group showed a significant decrease at 4 wk (P = 0.03 compared with CON). Moreover, the reduction in fasting glucose in the LCHP+ω-3 diet group (-1.32 mmol/L; 95% CI: -1.72, -0.93 mmol/L) was greater than that in the LCHP (P = 0.04) and ω-3 (P = 0.03) diet groups at 12 wk. Conclusions The LCHP+ω-3 diet provided greater effects on HbA1c and fasting glucose and faster effects on fasting glucose than both the LCHP and ω-3 diets, indicating the potential necessity of combining an LCHP diet with ω-3 PUFAs in T2D control. This trial was registered at chictr.org.cn/ as ChiCTR-TRC-14004704.

Brain derived neurotrophic factor (BDNF) is a protein that plays a critical role in modulating cognition in animals and humans. Aerobic exercise often increases BDNF in adults, but effects of this exercise modality and others among adolescents remain uncertain. This study examined the effects of aerobic training, resistance training, and combined training on resting serum BDNF levels in adolescents with overweight and obesity. After a 4-week pre-randomization treatment, 304 post-pubertal, adolescents with overweight or obesity (70% females) aged 14–18 years were randomized to one of four groups for 22 weeks: aerobic training (N = 75), resistance training (N = 78), combined aerobic and resistance training (N = 75), or non-exercising control (N = 76). All participants received dietary counseling targeting a daily energy deficit of 250 kcal. The exercise prescription was 4 times per week, progressing to 45 min/session for the aerobic and resistance groups and 90 min/session for the combined group. Resting serum BDNF levels were measured at baseline and 6-months. Results showed that in both intention-to-treat (ITT) and per protocol (≥70% adherence to prescribed sessions) analyses, there were no significant within- or between-group changes in BDNF. Findings indicate that aerobic training, resistance training or their combination did change serum BDNF levels in adolescents with overweight and obesity. Trial Registration: ClinicalTrials.Gov NCT00195858 http://clinicaltrials.gov/show/NCT00195858, September 12, 2005 (Funded by the Canadian Institutes of Health Research).