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BACKGROUND Low anterior resection syndrome has a significant impact on the quality of life in rectal cancer survivors. Previous studies comparing laparoscopic to open rectal resection have neglected bowel function outcomes. OBJECTIVE To assess if there is a difference in the functional outcome between patients undergoing laparoscopic versus open resection for rectal adenocarcinoma. DESIGN Cross-sectional prevalence of low anterior resection syndrome was assessed in a secondary analysis of the multi-center phase 3 randomized clinical trial, Australasian Laparoscopic Cancer of the Rectum Trial (ACTRN12609000663257). SETTING Seven study subsites across New Zealand and Australia. PATIENTS Participants were adults with rectal cancer who underwent anterior resection and had bowel continuity. MAIN OUTCOME MEASURES Postoperative bowel function was evaluated using the validated LARS score and Bowel Function Instrument. RESULTS The Australasian Laparoscopic Cancer of the Rectum Trial randomized 475 patients with T1-T3 rectal adenocarcinoma less than 15cm from the anal verge. 257 participants were eligible for, and invited to, participate in additional follow-up. 163 (63%) completed functional follow-up. Overall cross-sectional prevalence of major LARS was 49% (minor LARS 27%). There were no differences in median overall Bowel Function Instrument score nor LARS score between participants undergoing laparoscopic vs. open surgery (66 vs 67, p = 0.52; 31 vs 27, p = 0.24) at a median follow-up of 69 months. LIMITATIONS The major limitations are a result of conducting a secondary analysis; the likelihood of an insufficient sample size to detect a difference in prevalence between the groups and the possibility of selection bias as a subset of the randomized population was analyzed. CONCLUSIONS Bowel dysfunction affects a majority of rectal cancer patients for a significant time after the operation. In this secondary analysis of a randomized trial, surgical approach does not appear to influence the likelihood or severity of low anterior resection syndrome. See Video Abstract at http://links.lww.com/DCR/B794.

Background: The association between intraoperative estimated blood loss and outcomes after pancreatoduodenectomy has, thus far, been rarely explored. Methods: In total, 7,706 pancreatoduodenectomies performed at 18 international institutions composing the Pancreas Fistula Study Group were examined (2003-2020). High estimated blood loss (>700 mL) was defined as twice the median. Propensity score matching (1:1 exact-match) was employed to adjust for variables associated with high estimated blood loss and clinically relevant pancreatic fistula occurrence. The study was powered to detect a 33% clinically relevant pancreatic fistula increase in the high estimated blood loss group, with a = 0.05 and b = 0.2. Results: The propensity score model included 966 patients with high estimated blood loss and 966 patients with lower estimated blood loss; all covariate imbalantces were solved. Patients with high estimated blood loss patients experienced higher clinically relevant pancreatic fistula rates (19.4 vs 12.6%, odds ratio 1.66; P < .001), as well as higher severe complication rates (27.8 vs 15.6%), transfusions (50.1 vs 14.3%), reoperations (9.2 vs 4.0%), intensive care unit transfers (9.9 vs 4.8%) and 90-day mortality (4.7 vs 2.0%, all P < .001). High estimated blood loss was an independent predictor for clinically relevant pancreatic fistula (odds ratio 1.78, 95% confidence interval 1.37-2.32), as were prophylactic Octreotide administration (odds ratio 1.95, 95% confidence interval 1.46-2.61) and soft pancreatic texture (odds ratio 5.32, 95% confidence interval 3.74-5.57; all P < .001). Moreover, a second model including 1,126 pancreatoduodenectomies was derived including vascular resections as additional confounder (14.0% vascular resections performed in each group). On multivariable regression, high estimated blood loss was confirmed an independent predictor for clinically relevant pancreatic fistula reduction (odds ratio 1.80, 95% confidence interval 1.32-2.4 4; P < .001), whereas vascular resection was not (odds ratio 0.64, 95% confidence interval 0.34-1.88; P 1/4 .156). Conclusion: This study better establishes the relationship between estimated blood loss and outcomes after pancreatoduodenectomy. Despite inherent contributions to blood loss, its minimization is an actionable opportunity for clinically relevant pancreatic fistula reduction and performance optimization in pancreatoduodenectomy. Accordingly, practical insights are offered to achieve this goal. (c) 2021 Elsevier Inc. All rights reserved.

Intraperitoneal drain placement decreases morbidity and mortality in patients who develop a clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). It is unknown whether multiple drains mitigate CR-POPF better than a single drain. We hypothesized that multiple drains decrease the complication burden more than a single drain in cases at greater risk for CR-POPF.The Fistula Risk Score (FRS), mitigation strategies (including number of drains placed), and clinical outcomes were obtained from a multi-institutional database of PDs performed from 2003 to 2020. Outcomes were compared between cases utilizing 0, 1, or 2 intraperitoneal drains. Multivariable regression analysis was used to evaluate the optimal drainage approach.A total of 4,292 PDs used 0 (7.3%), 1 (45.2%), or 2 (47.5%) drains with an observed CR-POPF rate of 9.6%, which was higher in intermediate/high FRS zone cases compared with negligible/low FRS zone cases (13% vs 2.4%, P.001). The number of drains placed also correlated with FRS zone (median of 2 in intermediate/high vs 1 in negligible/low risk cases). In intermediate/high risk cases, the use of 2 drains instead of 1 was not associated with a reduced rate of CR-POPF, average complication burden attributed to a CR-POPF, reoperations, or mortality. Obviation of drains was associated with significant increases in complication burden and mortality - regardless of the FRS zone.In intermediate/high risk zone cases, placement of a single drain or multiple drains appears to mitigate the complication burden while use of no drains is associated with inferior outcomes.

The eighth edition of the American Joint Committee on Cancer classifies nonmetastatic, node-negative colorectal cancers invading the submucosa (T1) and muscularis propria (T2) as stage I tumors without additional subclassification.The aim of the study was to compare survival of T1N0M0 versus T2N0M0 colorectal cancers and to investigate factors associated with decreased survival.This was an analysis of 2 large population-based data sets.The study was conducted analyzing data from the Surveillance Epidemiology and End Result program and the National Cancer Database.Adult patients undergoing major resection without additional therapy for stage I colorectal cancer were included.Overall and disease-specific survival for T1 versus T2 cancers were measured. Subgroup analyses by tumor location (colon versus rectum) were performed.A total of 30,228 (36.4% T1 and 63.6% T2) and 41,670 (41.1% T1 and 58.9% T2) patients were identified in the Surveillance Epidemiology and End Result database and the National Cancer Database. The 5-year overall survival rates were 87.1% and 86.2% for patients with T1 versus 82.7% and 80.7% for patients with T2 (p0.001) in the Surveillance Epidemiology and End Result database and the National Cancer Database. The 10-year overall survival rates were 71.3% and 66.3% for patients with T1 versus 62.2% and 57.2% for patients with T2 tumors (p0.001) in the Surveillance Epidemiology and End Result database and the National Cancer Database. The 5- and 10-year disease-specific survival for colorectal cancer in the Surveillance Epidemiology and End Result database was 97.0% (T1) versus 95.2% (T2) and 94.1% (T1) versus 90.3% (T2). Black race (HR = 1.26 and 1.65 for overall survival and disease-specific survival in the Surveillance Epidemiology and End Result database; HR = 1.20 for overall survival in the National Cancer Database) was associated with worse survival.The study was limited by intrinsic biases related to large administrative data sets.Within stage I colorectal cancer, T2 tumors have decreased overall survival and disease-specific survival as compared with T1 cancers. This survival difference may justify revising the American Joint Committee on Cancer staging system to include the subclassification of stage Ia (T1N0M0) and stage Ib (T2N0M0). See Video Abstract at http://links.lww.com/DCR/B659.ANTECEDENTES:La octava edición del American Joint Committee on Cancer, clasifica los cánceres colorrectales no metastásicos con ganglios negativos, que invaden la submucosa (T1) y la muscularis propia (T2) como tumores en estadio I sin subclasificación adicional.OBJETIVO:El objetivo del estudio fue comparar la sobrevida de los cánceres colorrectales T1N0M0 versus T2N0M0 e investigar los factores asociados con la disminución de la sobrevida.DISEÑO:Análisis de dos grandes conjuntos de datos poblacionales.MARCO:El estudio se realizó analizando datos del Programa de Epidemiología de Vigilancia y Resultados Finales (SEER) y la Base de Datos Nacional del Cáncer.PACIENTES:Pacientes adultos en los cuales se realizó una resección mayor sin terapia adicional por cáncer colorrectal en estadio I.PRINCIPALES VARIABLES ANALIZADAS:Sobrevida global y específica de la enfermedad para los cánceres T1 versus T2. Se realizó un análisis de subgrupos según la ubicación del tumor (colon versus recto).RESULTADOS:Se incluyeron un total de 30.228 (36,4% T1 y 63,6% T2) y 41.670 (41,1% T1 y 58,9% T2) pacientes en las bases de datos SEER y la Base de Datos Nacional del Cáncer, respectivamente. La sobrevida global a 5 años fue del 87,1% y el 86,2% para los pacientes con T1 frente al 82,7% y el 80,7% de los pacientes con T2 (p0,001) en el SEER y la Base de Datos Nacional del Cáncer, respectivamente. La sobrevida global a 10 años fue del 71,3% y el 66,3% para los pacientes con T1 frente al 62,2% y el 57,2% de los pacientes con tumores T2 (p0,001) en el SEER y la Base de Datos Nacional del Cáncer, respectivamente. La sobrevida específica de la enfermedad a 5 y 10 años para el cáncer colorrectal en el SEER fue del 97,0% (T1) frente al 95,2% (T2) y del 94,1% (T1) frente al 90,3% (T2), respectivamente. La grupo étnico afroamericano se asoció con una sobrevida menor (Hazard Ratio -HR 1,26 y 1,65 para la sobrevida general y sobrevida específica de la enfermedad-SEER; HR 1,20 para la sobrevida general-Base de de Datos Nacional del Cáncer).LIMITACIONES:Sesgos intrínsecos relacionados con el análisis de grandes conjuntos de datos.CONCLUSIONES:Dentro del cáncer colorrectal en estadio I, los tumores T2 han disminuido la sobrevida general y la sobrevida específica de la enfermedad, en comparación con los cánceres T1. Esta diferencia de sobrevida puede justificar la revisión del sistema de estadificación del American Joint Committee on Cancer para incluir la subclasificación del estadio Ia (T1N0M0) y el estadio Ib (T2N0M0). Consulte Video Resumen en http://links.lww.com/DCR/B659.

Pulmonary CTA is a ubiquitous study interpreted by radiologists with different levels of experience in a variety of practice settings. Pulmonary embolism (PE) can range from an incidental and clinically insignificant finding to a clinically significant thrombus that can be managed on an outpatient basis to a potentially fatal condition requiring immediate medical or invasive management. Accordingly, a clear and concise pulmonary CTA report should effectively communicate the most pertinent findings to help the treating medical team diagnose or exclude the diagnosis of PE and provide information to guide appropriate management. In this expert panel narrative review, we discuss the purpose of the radiology report for pulmonary CTA, the optimal report format, the relevant findings that need to be addressed and their clinical significance.

Background The Nuss procedure for pectus excavatum has historically been associated with significant postoperative pain, which has been the major factor contributing to hospital length of stay (LOS). Methods A single-institution, prospective study of 40 consecutive patients undergoing Nuss bar placement for pectus excavatum between November 2019 and January 2021 was conducted to assess the effectiveness of a multimodality pain management protocol. All patients received T3-T8 intercostal nerve cryoablation (INC), T3-T8 bupivacaine intercostal nerve blocks, Exparel at the skin incisions, and management with a perioperative analgesia regimen that minimized narcotic usage. The primary outcome was LOS. Secondary outcomes included opioid use, pain scores, and time to sensory recovery. Results 37/40 patients (92.5%) were discharged home on postoperative day (POD) 1, and 3/40 (7.5%) were discharged on POD 2 (mean LOS = 1.1 days). The median average postoperative pain score was 2/10. After eliminating IVPCA from our protocol, total oral morphine equivalent (OME) decreased by 73% (55.5 mg to 15 mg) with no change in pain scores or discharge timing. Conclusions INC combined with bupivacaine intercostal nerve blocks and a pre- and post-hospital analgesia protocol facilitated discharge one day after the Nuss procedure, achieved excellent pain control, and eliminated the need for intravenous opioids.

Background Although hidradenitis suppurativa (HS) shares some transcriptomic and cellular infiltrate features with psoriasis, their skin proteome remains unknown. Objective To define and compare inflammatory protein biomarkers of HS and psoriasis skin. Methods We assessed 92 inflammatory biomarkers in HS (n = 13), psoriasis (n = 11), and control skin (n = 11) using Olink high-throughput proteomics. We also correlated HS skin and blood biomarkers using proteomics and RNA sequencing. Results We identified 57 differentially expressed proteins (DEPs) in lesional psoriasis and 64 DEPs in lesional HS skin, compared to healthy controls. Both HS and psoriasis lesional skin demonstrated a significant upregulation of T helper 1 and T helper 17 proteins. Healthy-appearing perilesional HS skin had 63 DEPs compared to healthy controls. Nonlesional HS and psoriasis skin had 24 and 7 DEPs, respectively, compared to healthy controls. Tumor necrosis factor and 8 other proteins were significantly correlated with clinical severity in perilesional HS skin (2 cm from a nodule). Limitations Inclusion of only moderate-to-severe patients and the cohort size. Conclusion HS has a greater inflammatory profile and is more diffusely distributed compared with psoriasis. Proteins correlated with disease severity are potential disease mediators. Perilesional skin is comparably inflamed to lesional skin, suggesting the need to treat beyond skin nodules.

Background and aims Recent evidence links trimethylamine oxide (TMAO) to endothelial dysfunction, an early indicator of cardiovascular disease. We aimed to determine whether short-term consumption of a diet patterned after the 2010 Dietary Guidelines for Americans (DGA) would affect endothelial function, plasma TMAO concentrations, and cardiovascular disease risk, differently than a typical American Diet (TAD). Methods and results An 8-wk controlled feeding trial was conducted in overweight/obese women pre-screened for insulin resistance and/or dyslipidemia. Women were randomized to a DGA or TAD group (n = 22/group). At wk0 (pre-intervention) and wk8 (post-intervention) vascular age was calculated; endothelial function (reactive hyperemia index (RHI)) and augmentation index (AI@75) were measured using EndoPAT, and plasma TMAO was measured by LC-MS/MS. Vascular age was reduced in DGA at wk8 compared to wk0 but TAD wk8 was not different from wk0 (DGA wk0: 54.2 ± 4.0 vs. wk8: 50.5 ± 3.1 (p = 0.05), vs. TAD wk8: 47.7 ± 2.3). Plasma TMAO concentrations, RHI, and AI@75 were not different between groups or weeks. Conclusion Consumption of a diet based on the 2010 Dietary Guidelines for Americans for 8 weeks did not improve endothelial function or reduce plasma TMAO. ClinicalTrials.gov NCT02298725.

Neuro-endocrine prostate cancer (NEPC) accounts for about 20% of lethal metastatic castration-resistant prostate cancer (CRPC). NEPC has the most aggressive biologic behavior of all prostate cancers and is associated with poor patient outcome. Effective treatment for NEPC is not available because NEPC exhibit distinct cell-surface expression profiles compared to other types of prostate cancer. Recently, the carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) (known as CEA or CD66e) was suggested to be a specific surface protein marker for NEPC. Therefore, we identified a new, fully-human anti-CEACAM5 monoclonal antibody, 1G9, which bound to the most proximal membrane domains, A3 and B3, of CEACAM5 with high affinity and specificity. It shows no off-target binding to other CEACAM family members, membrane distal domains of CEACAM5, or 5800 human membrane proteins. IgG1 1G9 exhibited CEACAM5-specific ADCC activity toward CEACAM5-positive prostate cancer cells in vitro and in vivo. Chimeric antigen receptor T cells (CAR-T) based on scFv 1G9 induced specific and strong antitumor activity in a mouse model of prostate cancer. Our results suggest that IgG1 and CAR-T cells based on 1G9 are promising candidate therapeutics for CEACAM5-positive NEPC and other cancers.

Facial paralysis may result in significant functional, esthetic, and psychological morbidity. Mobius syndrome is a form of bilateral congenital facial paralysis that is particularly difficult to treat owing to the lack of readily available donor nerves, particularly in the upper face. In this study, we evaluate the feasibility of using the deep temporal nerves as donors for the innervation of free muscle grafts in the periorbital region. Preserved and fresh cadaver facial halves are dissected, and the course of the deep temporal nerves delineated. We find the middle branch of the deep temporal nerve to be located consistently 4.6 cm from the posterior edge of the tragus along the zygomatic arch, giving an easily identifiable surface landmark for our donor. Finally, we outline a proposed surgical approach for using the middle deep temporal nerve to innervate a free muscle graft to the eyelids through an interpositional nerve graft.

BACKGROUND The 2020 European Society of Cardiology (ESC) guidelines recommend using the 0/1-hour and 0/2-hour algorithms over the 0/3-hour algorithm as the first and second choices of high-sensitivity cardiac troponin (hs-cTn)-based strategies for triage of patients with suspected acute myocardial infarction (AMI). PURPOSE To evaluate the diagnostic accuracies of the ESC 0/1-hour, 0/2-hour, and 0/3-hour algorithms. DATA SOURCES PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from 1 January 2011 to 31 December 2020. (PROSPERO: CRD42020216479). STUDY SELECTION Prospective studies that evaluated the ESC 0/1-hour, 0/2-hour, or 0/3-hour algorithms in adult patients presenting with suspected AMI. DATA EXTRACTION The primary outcome was index AMI. Twenty unique cohorts were identified. Primary data were obtained from investigators of 16 cohorts and aggregate data were extracted from 4 cohorts. Two independent authors assessed each study for methodological quality. DATA SYNTHESIS A total of 32 studies (20 cohorts) with 30 066 patients were analyzed. The 0/1-hour algorithm had a pooled sensitivity of 99.1% (95% CI, 98.5% to 99.5%) and negative predictive value (NPV) of 99.8% (CI, 99.6% to 99.9%) for ruling out AMI. The 0/2-hour algorithm had a pooled sensitivity of 98.6% (CI, 97.2% to 99.3%) and NPV of 99.6% (CI, 99.4% to 99.8%). The 0/3-hour algorithm had a pooled sensitivity of 93.7% (CI, 87.4% to 97.0%) and NPV of 98.7% (CI, 97.7% to 99.3%). Sensitivity of the 0/3-hour algorithm was attenuated in studies that did not use clinical criteria (GRACE score

Despite significant improvements in reperfusion strategies, acute coronary syndromes all too often culminate in a myocardial infarction (MI). The consequent MI can, in turn, lead to remodeling of the left ventricle (LV), the development of LV dysfunction, and ultimately progression to heart failure (HF). Accordingly, an improved understanding of the underlying mechanisms of MI remodeling and progression to HF is necessary. One common approach to examine MI pathology is with murine models that recapitulate components of the clinical context of acute coronary syndrome and subsequent MI. We evaluated the different approaches used to produce MI in mouse models and identified opportunities to consolidate methods, recognizing that reperfused and nonreperfused MI yield different responses. The overall goal in compiling this consensus statement is to unify best practices regarding mouse MI models to improve interpretation and allow comparative examination across studies and laboratories. These guidelines will help to establish rigor and reproducibility and provide increased potential for clinical translation. Listen to another corresponding podcast at https://ajpheart.podbean.com/e/guidelines-for-in-vivo-mouse-models-of-myocardial-infarction/ .

Hidradenitis Suppurativa (HS) is a chronic inflammatory disease of the skin with a predilection for women. The role of sex hormones, including estrogen and progesterone, is incompletely understood, but alterations in hormone levels may play a role in disease activity for many patients. Specific clinical considerations should be made for women with HS, particularly in the setting of pregnancy, childbirth, breastfeeding, and menopause. Current knowledge gaps regarding HS include the cumulative impact of disease across an individual's lifespan, as well as the mechanistic role of sex hormones in the disease. An improved understanding of the pathophysiologic role of hormones in HS would optimize our ability to utilize targeted therapies for hormonally driven disease. Psychological and psychosexual support for women with HS is an important facet of any holistic management strategy for the disease. This article integrates up to date pathogenic and mechanistic insights with evidence based clinical management to optimize care for women with HS.

Achalasia is a rare chronic esophageal motility disorder characterized by incomplete relaxation of the lower esophageal sphincter and abnormal peristalsis. This abnormal motor function leads to impaired bolus emptying and symptoms of dysphagia, regurgitation, chest pain, or heartburn. After an upper endoscopy to exclude structural causes of symptoms, the gold standard for diagnosis is high-resolution esophageal manometry. However, complementary diagnostic tools include barium esophagram and functional luminal impedance planimetry. Definitive treatments include pneumatic dilation, Heller myotomy with fundoplication, and peroral endoscopic myotomy.

Background Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatologic disease that occurs in the pediatric population. Often, JIA continues throughout life leading to progressive polyarticular arthritis and significant joint destruction and disability, oftentimes requiring replacement surgery. This study aimed to determine the outcomes of primary shoulder arthroplasty (SA) in patients with JIA. Methods Over a 42-year time period (1977 - 2019), 67 primary SA (20 hemiarthroplasty (HA), 38 anatomic total shoulder arthroplasty (TSA), and 9 reverse shoulder arthroplasty (RSA)) with a prior diagnosis of JIA formally established in a multi-disciplinary rheumatologic clinic met inclusion criteria. Further assessment was performed with inclusion of the visual analog scale (VAS) pain score, active shoulder range of motion (ROM), imaging studies, complications, and implant survivorship free from reoperation and revision. Results SA led to substantial improvements in pain and ROM across the entire cohort at an average follow-up period of 12.2 years (range, 2- 34 years). TSA was associated with the lowest pain scores (0.8; p = 0.02) and the highest ASES scores (77.4; p = 0.04) at most recent follow-up when compared to HA and RSA. There were 14 (21%) complications across the cohort with rotator cuff failure (n=4; 5.9%) as the most common complication followed by infection (n=3; 4.5%). Revision surgery was performed in 5 shoulders (7.5%), with five-year implant survival rates of 95.1% at five years, 93% at ten years, 89.4% at twenty years, and 79.5% at thirty years. At 30 years, TSA was associated with better survival (90.1%) when compared with HA (71.8%). Conclusions Primary shoulder arthroplasty in the form of HA, TSA, and RSA offers a reliable surgical option for JIA patients with respect to pain reduction and ROM improvements. Unique challenges still exist in this cohort, in particular younger patients with an elevated propensity for glenoid bone erosion and a complication rate of 20.9%. As such, HA may not be ideal in this patient population. However, despite rotator cuff and glenoid concerns, TSA seems to be associated with better pain relief and patient reported outcomes with the most durability in the long term when compared to HA. Level of evidence Level III; Retrospective Cohort Comparison; Treatment Study.

Background Infection by SARS‐CoV‐2 produces significant pulmonary pathology including endothelial damage with resultant thrombotic events. While pathologic features were described, there are limited data on the relationship of these changes to the inflammatory response and the production of thromboses. Objective To investigate pathology of COVID‐19‐related immunothrombosis. Patients/Methods Tissue samples from lung, kidney, brain and heart that were collected from 45 patients who died of COVID‐19. Histopathological examination was performed after H&E and Picro‐Mallory staining in combination with (immuno)fluorescence to visualize neutrophil extracellular traps. Ultrastructural alterations in lungs were studied with scanning and transmission electron microscopy. Results Inflammatory changes and thrombosis were substantially more pronounced in the lung than in the kidney, heart, and brain. The most common pathologic finding was diffuse alveolar damage. In addition, most lung samples showed thrombi in vessels. The cause of death in single cases was massive pulmonary embolism. Ultrastructural examination revealed neutrophils attached to endothelium, perhaps as a step towards transendothelial migration. In addition, platelets were identified in the midst of fibrin as individual procoagulant balloon‐like cells. Ultrastructural examination demonstrated numerous virion‐like particles. Conclusions Studying (ultra)structural features of the autopsy lung samples from patients with COVID‐19 has provided evidence for a pathogenic link between inflammation and thrombosis. The major features in the lungs of COVID‐19 patients comprised primary inflammatory thrombosis associated with diffuse alveolar damage. The lungs had pronounced circulatory changes with inflammation‐dependent intravascular blood clotting, whereas heart, brain, and kidneys had predominantly degenerative changes that were distinct from the lung pathology.

Globally, ruminant production contributes immensely to the supply of the highest quality and quantity of proteins for human consumption, sustenance of livelihoods, and attainment of food security. Nevertheless, the phasing out of antibiotics in animal production has posed a myriad of challenges, including poor growth, performance and nutrient utilization, pathogen colonization, dysbiosis, and food safety issues in ruminants. Probiotics (direct-fed microbials), comprising live microbial strains that confer health and nutritional benefits to the host when administered in appropriate quantities, are emerging as a viable, safe, natural and sustainable alternative to antibiotics. Although the mechanisms of action exerted by probiotics on ruminants are not well elucidated, dietary probiotic dosage to ruminants enhances development and maturation, growth and performance, milk production and composition, nutrient digestibility, feed efficiency, pathogen reduction, and mitigation of gastrointestinal diseases. However, the beneficial response to probiotic supplementation in ruminants is not consistent, being dependent on the microbial strain selected, combination of strains, dose, time and frequency of supplementation, diet, animal breed, physiological stage, husbandry practice, and farm management. Nonetheless, several studies have recently reported beneficial effects of probiotics on ruminant performance, health and production. This review conclusively re-iterates the need for probiotics inclusion for the sustainability of ruminant production. Considering the role that ruminants play in food production and employment, global acceptance of sustainable ruminant production through supplementation with probiotics will undoubtedly ensure food security and food safety for the world. © 2021 Society of Chemical Industry.

Combined heart-liver transplant is an emerging option for patients with indications for heart transplantation and otherwise prohibitive hepatic dysfunction. Heart-liver transplantation is particularly relevant for patients with single ventricle physiology who often develop Fontan-associated liver disease and fibrosis. While only performed at a limited number of centers, several approaches to combined heart-liver transplantation have been described. The en bloc technique offers several potential advantages over the traditional sequential technique. Specifically, en bloc heart-liver transplantation may allow improved hemodynamics, decreased bleeding, reduced liver allograft ischemic time, and may result in reduced rates of graft dysfunction. Here we describe our center's en bloc heart-liver procurement technique in detail, with the aim of allowing broader use and standardization of this technique. Supplemental Visual Abstract; http://links.lww.com/TP/C147.

Background Erythrocyte transfusions are independently associated with acute kidney injury. Kidney injury may be consequent to the progressive hematologic changes that develop during storage. This study therefore tested the hypothesis that prolonged erythrocyte storage increases posttransfusion acute kidney injury. Methods The Informing Fresh versus Old Red Cell Management (INFORM) trial randomized 31,497 patients to receive either the freshest or oldest available matching erythrocyte units and showed comparable mortality with both. This a priori substudy compared the incidence of posttransfusion acute kidney injury in the randomized groups. Acute kidney injury was defined by the creatinine component of the Kidney Disease: Improving Global Outcomes criteria. Results The 14,461 patients included in this substudy received 40,077 erythrocyte units. For patients who received more than one unit, the mean age of the blood units was used as the exposure. The median of the mean age of blood units transfused per patient was 11 days [interquartile range, 8, 15] in the freshest available blood group and 23 days [interquartile range, 17, 30] in the oldest available blood group. In the primary analysis, posttransfusion acute kidney injury was observed in 688 of 4,777 (14.4%) patients given the freshest available blood and 1,487 of 9,684 (15.4%) patients given the oldest available blood, with an estimated relative risk (95% CI) of 0.94 (0.86 to 1.02; P = 0.132). The secondary analysis treated blood age as a continuous variable (defined as duration of storage in days), with an estimated relative risk (95% CI) of 1.00 (0.96 to 1.04; P = 0.978) for a 10-day increase in the mean age of erythrocyte units. Conclusions In a population of patients without severely impaired baseline renal function receiving fewer than 10 erythrocyte units, duration of blood storage had no effect on the incidence of posttransfusion acute kidney injury. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

BACKGROUND Tomatoes contain carotenoids that have the potential to alter the effects of external beam radiation therapy (EBRT). OBJECTIVES We hypothesized that dietary lyophilized tomato paste (TP) would reduce apoptosis within carotenoid-containing nonneoplastic tissues in EBRT-treated TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice. METHODS Male TRAMP mice (n = 73) were provided an AIN-93G diet or a modified AIN-93G diet containing 10% TP (wt:wt) at 4 wk of age. Prostate tumor growth was monitored by ultrasound. The caudal half of the mouse was irradiated with 7.5 Gy (Rad) or 0 Gy (sham) at 24 wk of age or after the tumor volume exceeded 1000 mm3 with a Cobalt-60 source. Mice were euthanized 24 h postradiation. Carotenoids and α-tocopherol were measured by HPLC and compared by a t test. Tissues were assessed for radiation-induced changes (hematoxylin and eosin) and apoptosis [cleaved caspase-3 (CC3)] and compared by Kruskal-Wallis test or Freedman-Lane's permutation test. RESULTS Serum concentrations of lycopene (52% lower), phytoene (26% lower), and α-tocopherol (22% lower) were decreased in TP-fed irradiated mice (TP-Rad) compared with TP-fed sham mice (P

BACKGROUND/PURPOSE To identify geographic and socioeconomic variables predictive of residential proximity to retinopathy of prematurity (ROP) clinical trial locations. METHODS This cross-sectional epidemiological study used census tract-level data from three national public data sets and trial-level data from ClinicalTrials.gov. Socioeconomic predictors of driving distance and time to the nearest ROP clinical trial location were identified. Primary outcomes were time >60 minutes and distance >60 miles traveled to the nearest ROP clinical trial site. RESULTS Multivariate analysis showed that residents were more likely to travel >60 minutes to the nearest ROP clinical trial site if they lived in census tracts that were rural (adjusted odds ratio 1.20, P = 0.0002), had higher percentages of the population living ≤ federal poverty level (fourth quartile vs. first quartile, adjusted odds ratio 1.19, P 60 minutes. Similar variables predicted travel distance. CONCLUSION Although counties with higher incidences of very low-birth-weight infants were closer to ROP clinical trial sites, residents living in rural and low-income census tracts had significantly greater travel burdens.

Background Refugees in Malaysia, who are afflicted by poverty, conflict and poor health, are vulnerable to a range of zoonotic infections in the deprived environmental and social conditions under which they live. Exposure to infections such as leptospirosis, for which rodents are primary hosts, is of particular concern. Methods A wellness program was conducted to determine the presence of antibodies against Leptospira (seroprevalence) in 11 refugee community schools and centers in the Klang Valley, Malaysia. A total of 433 samples were assessed for IgG and IgM antibodies against Leptospira, using enzyme-linked immunosorbent assays (ELISA). Results Overall Leptospira seroprevalence was 24.7%, with 3.0% being seropositive for anti-Leptospira IgG and 21.7% for anti-Leptospira IgM. Factors significantly associated with overall Leptospira seroprevalence included: age, ethnicity, pet ownership, knowledge of disease and awareness of disease fatality. For IgM seroprevalence, significant risk factors included sex, ethnicity, eating habits with hands, pet ownership, the presence of rats, walking in bare feet and water recreation visits. Conclusions These findings highlight the need for improvements in health and well-being among the refugee community through disease awareness programs and provision of healthy behavior programs, particularly in hygiene and sanitation through community engagement activities.

Importance Arthroscopic suprapectoral biceps tenodesis (ABT) and open subpectoral biceps tenodesis (OBT) are two surgical treatment options for relief of long head of the biceps tendon (LHBT) pathology and superior labrum anterior to posterior (SLAP) tears. There is insufficient knowledge regarding the clinical superiority of one technique over the other. Objective To systematically review the literature in order to compare the clinical outcomes and safety of ABT and OBT for treatment of LHBT or SLAP pathology. Evidence review A systematic review was performed by searching PubMed, the Cochrane Library and Embase to identify studies that compared the clinical efficacy of ABT versus OBT. The search phrase used was: (bicep OR biceps OR biceps brachii OR long head of biceps brachii OR biceps tendinopathy) AND (tenodesis). Patients were assessed based on the American Shoulder and Elbow Surgeons Score, the visual analogue scale, the Single Assessment Numeric Evaluation, Constant-Murley Score, clinical failure, range of motion, bicipital groove pain and strength. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and both the Cochrane Collaboration’s and Risk of Bias in Non-randomised Studies - of Interventions (ROBINS-I) risk of bias tools were used to evaluate risk of bias. Findings Eight studies (one level I, seven level III) met inclusion criteria, including 326 patients undergoing ABT and 381 patients undergoing OBT. No differences were found in treatment failure rates or patient-reported outcome scores between groups in any study. One study found OBT patients to experience significantly increased range of shoulder forward flexion when compared with ABT patients (p=0.049). Two studies found ABT patients to experience significantly more postoperative stiffness when compared with OBT patients (p Conclusions Patients undergoing ABT and OBT can be expected to experience similar improvements in clinical outcomes at latest follow-up without differences treatment failure or functional performance. ABT patients may experience an increased incidence of stiffness in the early postoperative period. Level of evidence III.

Background Pulmonary hypertension is a progressive medical condition that has been identified as a risk factor for perioperative morbidity and mortality in both cardiac and non-cardiac surgery, including hip arthroplasty. Currently, there is very limited information on the impact of pulmonary hypertension (PHTN) on patients undergoing shoulder arthroplasty. This investigation analyzed the mortality, perioperative medical complications, implant survivorship, and clinical outcomes in this medically complex cohort. Methods Between January 2000 and July 2018, 380 primary and 59 revision shoulder arthroplasties were performed at a single institution in patients with a diagnosis of pulmonary hypertension prior surgery. Average age was 72.8 ± 11.0 and 72.1 ± 9.5 years for the primary and revision SA groups, respectively (P= .65). The median American Society of Anesthesiologists (ASA) scores were predominantly class 3 in both cohorts. Descriptions of group characteristics were calculated with student tests for numerical values. Mortality after primary and revision shoulder arthroplasties were individually calculated through a cumulative incidence analysis. Implant survivorship was analyzed with a competing risk model selecting death as the competing risk. Results The 90-day mortality was 1.6% for primary and 3.4% for revision SA, respectively. The cumulative incidences of death at 2, 5, 10, and 15 years were 16.5%, 43.3%, 80.8%, and 88.5% for primary and 12.1%, 44.7%, 64.4%, and 100% for revision arthroplasties, respectively. Medical complications were observed in 13.4% of primary and 42.4% of revision shoulder arthroplasties. These included respiratory failure and/or acute respiratory distress syndrome (3.2%), arrhythmia (2.7%), deep vein thrombosis (1.8%), and pulmonary embolism (1.6%). The 10-year cumulative incidences of revision for any reason were 4.5% in primary and 10.4% in revision shoulder arthroplasties. At final follow-up, the mean VAS and ASES scores were 2.3 ± 2.5 and 72.0 ± 18.5 in primary SA and 4.1 ± 2.9 and 51.8 ± 21.8 in revision SA. Conclusions A concomitant diagnosis of PHTN in patients undergoing primary or revision shoulder arthroplasty was associated with a high rate of perioperative medical complications and mortality rates at 90 days and at 10 years in both cohorts. This information should be considered to counsel patients, optimize their perioperative management, and anticipate a more complicated and costly postoperative recovery. Level of Evidence Level IV; Case Series with no Comparison Group

Cold injury can result from exercising at low temperatures and can impair exercise performance or cause lifelong debility or death. This consensus statement provides up-to-date information on the pathogenesis, nature, impacts, prevention, and treatment of the most common cold injuries.

Patients with Ehlers-Danlos syndrome (EDS) have high rates of shoulder instability, which place them at increased risk for instability-related arthropathy. Many studies have assessed outcomes for both primary and revision shoulder instability procedures in this patient population, but there is a paucity of data regarding the outcome of shoulder arthroplasty in EDS patients. The purpose of this study is to evaluate the results and complications of shoulder arthroplasty (SA) performed in a cohort of patients with EDS and compare them to a matched cohort of patients with no EDS.Over an 11-year period, 10 patients with EDS were identified at a single institution who underwent primary SA (6 anatomic total shoulder arthroplasties [aTSAs], 4 reverse shoulder arthroplasties [RTSAs]). Shoulders were evaluated at a mean follow-up of 60 months (range 25-97 months). This cohort was matched 1:2 based on age, sex, and year of surgery, with patients who underwent SA for either primary osteoarthritis (OA) for aTSA or cuff tear arthropathy for RTSA. EDS patients had a mean age of 55 years, mean body mass index of 26.1, and were all female. The primary outcome measures were postoperative pain, range of motion, complications, and reoperations.SA produced similar postoperative pain, range of motion, complications, and reoperations in patients with EDS vs. controls. EDS patients improved pre- to postoperative visual analog scale (VAS) pain score (6.5 to 1.7, P.001), elevation (96° to 138°, P = .04), and external rotation (36° to 57°, P = .16). Three EDS patients sustained postoperative complications (2 instability and 1 acromial fracture); however, no shoulder was reoperated.EDS patients undergoing SA can expect outcomes comparable to patients with primary OA or cuff tear arthropathy, with clinically meaningful improvements in pain and range of motion. Although EDS patients had no statistically significant increase in complications when compared to controls, their absolute rate of overall complications (3/10 patients; 30%) and postoperative instability (2/10 patients; 20%) in this small case series was relatively high and should be considered when performing SA.

Background: Anatomic total shoulder arthroplasty with a nonspherical humeral head and inlay glenoid replacement has been introduced in the past; however, clinical evidence remains limited. We hypothesized that patients with advanced glenohumeral arthritis demonstrate significant improvements in pain and function. Methods: Prospective patient-reported outcomes (PROs) included the American Shoulder and Elbow Surgeons score, a pain visual analog scale, and satisfaction. Range of motion was compared to the preoperative status. A sensitivity analysis examined responder rates and compared them to literature thresholds using the minimal clinically important difference and substantial clinical benefit. The preoperative glenoid morphology was determined using the Walsh classification. Zone-specific periprosthetic radiolucent lines were quantified at the last follow-up. Results: Thirty-nine shoulders in 36 patients (3 bilateral) with a mean age of 65.9 years (26 males, 13 females) and a mean follow-up of 41.0 months were included. Ninety-three percent had grade III osteoarthritis, and 7% grade II. The glenoid Walsh classification included A1 (25%), A2 (25%), B1 (22%), B2 (25%), and C (3%). All PROs improved significantly (P

Case We report the case of a 40-year-old woman with left shoulder pain and associated partial thickness rotator cuff disruption, biceps tendonitis, and subacromial bursitis. After primary rotator cuff repair with a bio-inductive implant, revision arthroscopy revealed a loose body and deltoid fascia impingement from a PEEK bone staple placed at the initial surgery, which resolved upon removal of the loose body and staple. Conclusion Proper insertion/utilization of the PEEK bone staples to ensure that they are inserted down to the bone and not proud is a simple solution that can be directly influenced by the treating surgeon.

BACKGROUND Cardiac magnetic resonance imaging (MRI) is becoming an alternative to right heart catheterization (RHC) for evaluating pulmonary hypertension (PH). A need exists to further evaluate cardiac MRI's ability to characterize PH. PURPOSE To evaluate the potential for four-dimensional (4D) flow MRI-derived pulmonary artery velocities to characterize PH. STUDY TYPE Prospective case-control. POPULATION Fifty-four PH patients (56% female); 25 controls (36% female). FIELD STRENGTH/SEQUENCE 1.5 T; gradient recalled echo 4D flow and balanced steady-state free precession cardiac cine. ASSESSMENT RHC was used to derive patients' pulmonary vascular resistance (PVR). 4D flow measured blood velocities at the main, left, and right pulmonary arteries (MPA, LPA, and RPA); cine measured ejection fraction, end diastolic, and end systolic volumes (EF, EDV, and ESV). EDV and ESV were normalized (indexed) to body surface area (ESVI and EDVI). Parameters were evaluated between, and within, PH subgroups: pulmonary arterial hypertension (PAH); PH due to left heart disease (PH-LHD)/chronic lung disease (PH-CLD)/or chronic thrombo-emboli (CTE-PH). STATISTICAL TESTS Analysis of variance and Kruskal-Wallis tests compared parameters between subgroups. Pearson's r assessed velocity, PVR, and volume correlations. Significance definition: P

AimTo develop a machine learning model to predict the diagnosis of pulmonary embolism (PE).Methods and resultsWe undertook a derivation and internal validation study to develop a risk prediction model for use in patients being investigated for possible PE. The machine learning technique, generalized logistic regression using elastic net, was chosen following an assessment of seven machine learning techniques and on the basis that it optimized the area under the receiver operator characteristic curve (AUC) and Brier score. Models were developed both with and without the addition of D-dimer. A total of 3347 patients were included in the study of whom, 219 (6.5%) had PE. Four clinical variables (O2 saturation, previous deep venous thrombosis or PE, immobilization or surgery, and alternative diagnosis equal or more likely than PE) plus D-dimer contributed to the machine learning models. The addition of D-dimer improved the AUC by 0.16 (95% confidence interval 0.13–0.19), from 0.73 to 0.89 (0.87–0.91) and decreased the Brier score by 14% (10–18%). More could be ruled out with a higher positive likelihood ratio than by the Wells score combined with D-dimer, revised Geneva score combined with D-dimer, or the Pulmonary Embolism Rule-out Criteria score. Machine learning with D-dimer maintained a low-false-negative rate at a true-negative rate of nearly 53%, which was better performance than any of the other alternatives.ConclusionA machine learning model outperformed traditional risk scores for the risk stratification of PE in the emergency department. However, external validation is needed.

Introduction: The large numbers of torture survivors suffering from post-traumatic stress disorder and other psychological trauma in the United States suggests pharmacists should be aware of, and attentive to possible drug therapies for this population. Method: To this end, we systematically review the literature on pharmacotherapy for survivors of torture. Published literature that assessed use of pharmacotherapy in torture victims were searched from MEDLINE, Cochrane Library, PsychInfo and CINAHL. Search terms “torture,” “pharmacotherapy,” “depression OR PTSD,” “refugee OR asylum seekers” and “treatment or rehabilitation” were utilized. Results: Review of controlled and uncontrolled studies reveal that antidepressants are the most widely studied medications, particularly sertraline, a selective-serotonin reuptake inhibitor, in the torture survivor population expanding to refugees and asylum seekers. Anti-adrenergic medications were used as adjunctive treatment in some uncontrolled studies. In randomized controlled trials, pharmacotherapy did not differentiate from placebo in reducing symptoms. Uncontrolled trials had yielded variable outcomes from pharmacotherapy. Discussion: There is lack of strong evidence in supporting the use of pharmacotherapy for the treatment of post-traumatic stress disorder and major depressive disorder. Heterogeneity in the study design, patient ethnicity and the social and political status at the time of the study may have contributed in the variable clinical responses to pharmacotherapy.

Objective To determine the prevalence and risk factors for inappropriate discharge on proton pump inhibitor (PPI) therapy started in the intensive care unit (ICU) for stress ulcer prophylaxis. Patients and Methods This was a retrospective cohort study of adults initiated on treatment with a PPI in any of 9 affiliated ICUs from January 1, 2014, to December 31, 2018. Patients were excluded if they had an appropriate long-term PPI indication. Logistic regression modeling was used to identify characteristics associated with discharge on treatment with an inappropriate PPI. Results Of 24,751 patients admitted to an ICU, 4127 were initiated on treatment with a new PPI, with 2467 (60%) lacking a long-term PPI indication. Of these 2467, a total of 1122 (45%) were continued on PPI therapy after transfer to the floor and 668 (27%) were discharged on PPI therapy. On multivariable analysis, risk factors for inappropriate discharge on PPI therapy included having an upper endoscopy (adjusted odds ratio [aOR], 1.70; 95% CI, 1.08-2.66), admission to the surgical compared with medical ICU (aOR, 2.03; 95% CI, 1.32-3.10), and discharge to a nursing home or rehabilitation facility (aOR, 1.43; 95% CI, 1.04-1.96; and aOR, 2.29; 95% CI, 1.62-3.24, respectively). Conclusion Among patients started on treatment with a PPI in the ICU without an indication for outpatient PPI use, 27% (668 of 2467) were nonetheless discharged on PPI therapy. Medically complex and surgical ICU patients are at increased risk for receiving PPIs without appropriate documented indications, and careful review of medication lists at discharge should occur in these high-risk groups.

Background: Earlier preclinical and phase II research showed enhanced effect of docetaxel plus intercalated erlotinib. The NVALT-18 phase III study was designed to compare docetaxel with docetaxel plus intercalated erlotinib in relapsed metastasized non-squamous (NSQ) non-small cell lung cancer (NSCLC).Methods: Patients with relapsed Epidermal Growth Factor Receptor (EGFR) wild type (WT) NSQ-NSCLC were randomized 1:1 to docetaxel 75 mg/m(2) intravenously on day 1 every 21 days (control), or docetaxel 75 mg/m(2) intravenously on day 1 plus erlotinib 150 mg/day orally on day 2-16 every 21 days (experimental arm). Progression free survival (PFS) was the primary endpoint, secondary objectives were duration of response, overall survival (OS) and toxicity.Results: Between October 2016 and April 2018 a total of 45 patients were randomized and received treatment in the control (N = 23) or experimental arm (N = 22), the study was stopped due to slow accrual. Median PFS was 4.0 months (95% CI: 1.5-7.1) versus 1.9 months (95% CI 1.4-3.5), p = 0.01 respectively; adjusted hazard ratio (HR) 2.51 (95% CI: 1.16-5.43). Corresponding median OS was 10.6 months (95% CI: 7.0-8.6) versus 4.7 months (95% CI: 3.2-8.6), p = 0.004, with an adjusted HR of 3.67 (95% CI: 1.46-9.27). Toxicity was higher with combination therapy, with toxicity >= CTCAE grade 3 in N = 6 (26%) in the control arm and N = 17 (77%) in the experimental arm (p < 0.001), mainly consisting of gastrointestinal symptoms and leukopenia.Conclusions: Our study shows detrimental effects of docetaxel plus intercalated erlotinib, and strongly discourages further exploration of this combination in clinical practice.

Duchenne muscular dystrophy (DMD) is the second most common fatal genetic disease in humans and is characterized by the absence of a functional copy of the protein dystrophin from skeletal muscle. In dystrophin-negative humans and rodents, regenerated skeletal muscle fibers show abnormal branching. The number of fibers with branches and the complexity of branching increases with each cycle of degeneration/regeneration. Previously, using the mdx mouse model of DMD, we have proposed that once the number and complexity of branched fibers present in dystrophic fast-twitch EDL muscle surpasses a stable level, we term the “tipping point,” the branches, in and of themselves, mechanically weaken the muscle by rupturing when subjected to high forces during eccentric contractions. Here, we use the slow-twitch soleus muscle from the dystrophic mdx mouse to study prediseased “periambulatory” dystrophy at 2–3 wk, the peak regenerative “adult” phase at 6–9 wk, and “old” at 58–112 wk. Using isolated mdx soleus muscles, we examined contractile function and response to eccentric contraction correlated with the amount and complexity of regenerated branched fibers. The intact muscle was enzymatically dispersed into individual fibers in order to count fiber branching and some muscles were optically cleared to allow laser scanning confocal microscopy. We demonstrate throughout the lifespan of the mdx mouse that dystrophic slow-twitch soleus muscle is no more susceptible to eccentric contraction-induced injury than age-matched littermate controls and that this is correlated with a reduction in the number and complexity of branched fibers compared with fast-twitch dystrophic EDL muscles.

Supplemental Digital Content is available in the text., OBJECTIVES: Clinical trials evaluating the safety and effectiveness of sedative medication use in critically ill adults undergoing mechanical ventilation differ considerably in their methodological approach. This heterogeneity impedes the ability to compare results across studies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations convened a meeting of multidisciplinary experts to develop recommendations for key methodologic elements of sedation trials in the ICU to help guide academic and industry clinical investigators. DESIGN: A 2-day in-person meeting was held in Washington, DC, on March 28–29, 2019, followed by a three-round, online modified Delphi consensus process. PARTICIPANTS: Thirty-six participants from academia, industry, and the Food and Drug Administration with expertise in relevant content areas, including two former ICU patients attended the in-person meeting, and the majority completed an online follow-up survey and participated in the modified Delphi process. MEASUREMENTS AND MAIN RESULTS: The final recommendations were iteratively refined based on the survey results, participants’ reactions to those results, summaries written by panel moderators, and a review of the meeting transcripts made from audio recordings. Fifteen recommendations were developed for study design and conduct, subject enrollment, outcomes, and measurement instruments. Consensus recommendations included obtaining input from ICU survivors and/or their families, ensuring adequate training for personnel using validated instruments for assessments of sedation, pain, and delirium in the ICU environment, and the need for methodological standardization. CONCLUSIONS: These recommendations are intended to assist researchers in the design, conduct, selection of endpoints, and reporting of clinical trials involving sedative medications and/or sedation protocols for adult ICU patients who require mechanical ventilation. These recommendations should be viewed as a starting point to improve clinical trials and help reduce methodological heterogeneity in future clinical trials.

Epithelioid hemangioendothelioma is a rare malignant vascular sarcoma. Here we present a patient with a very large tumor arising from the superior vena cava, in whom a resection with negative margins was accomplished using venovenous bypass and bovine pericardial patch reconstruction of the superior vena cava.

OBJECTIVES: The objective of this study was to examine the psychometric properties of the Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL 4.0 GCS) in Duchenne muscular dystrophy (DMD), a rare, severely debilitating, and ultimately fatal neuromuscular disease. METHODS: Patients with DMD were recruited from 20 centres across nine countries as part of the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (NCT00468832). The psychometric properties of the PedsQL 4.0 GCS were examined using Rasch analysis. RESULTS: In total, 329 patients with DMD (mean age: 9 years, range: 3–18 years; 75% ambulatory) completed the PedsQL 4.0 GCS. The most difficult instrument items, expressing the greatest loss in HRQoL, were those associated with emotional well-being (e.g., being teased by other children, feeling sad, and not making friends), as opposed to somatic disability (e.g., lifting heavy objects, participating in sports, and running). The mean item and person fit residuals were estimated at 0.301 (SD: 1.385) and −0.255 (1.504), respectively. In total, 87% (20 of 23) of items displayed disordered thresholds, and many exhibited non-trivial dependency. The overall item-trait interaction [Formula: see text] value was 178 (115 degrees of freedom, p

Lichen planus (LP) is a chronic inflammatory disorder that often affects the skin, hair, nails, and mucus membranes. Although esophageal involvement has traditionally been felt to be rare, recent reports suggest that it is often unrecognized or misdiagnosed. The diagnoses of esophageal lichen planus can be challenging and is suspected based on patients' endoscopic and histologic findings and in the context of their clinical history and physical examination. Physicians must have an index of suspicion, particularly in older white women and in those patients with an atypical esophagitis or stricturing disease, which do not respond to traditional treatment. Currently, there are limited data on esophageal lichen planus patients, and no formal management guidelines for this disease, which all gastroenterologists will see in practice. This article reviews the etiology and histopathology of LP and provides a comprehensive discussion of the clinical features, diagnosis, and management of esophageal disease from the gastroenterologist's perspective. Finally, we address the esophageal complications of LP.

Oral corticosteroids (OCS) are frequently used for asthma treatment. This medication is highly effective for both acute and chronic diseases, but evidence indicates that indiscriminate OCS use is common, posing a risk of serious side effects and irreversible harm. There is now an urgent need to introduce OCS stewardship approaches, akin to successful initiatives that optimized appropriate antibiotic usage. The aim of this TSANZ (Thoracic Society of Australia and New Zealand) position paper is to review current knowledge pertaining to OCS use in asthma and then delineate principles of OCS stewardship. Recent evidence indicates overuse and over-reliance on OCS for asthma and that doses >1000 mg prednisolone-equivalent cumulatively are likely to have serious side effects and adverse outcomes. Patient perspectives emphasize the detrimental impacts of OCS-related side effects such as weight gain, insomnia, mood disturbances and skin changes. Improvements in asthma control and prevention of exacerbations can be achieved by improved inhaler technique, adherence to therapy, asthma education, smoking cessation, multidisciplinary review, optimized medications and other strategies. Recently, add-on therapies including novel biological agents and macrolide antibiotics have demonstrated reductions in OCS requirements. Harm reduction may also be achieved through identification and mitigation of predictable adverse effects. OCS stewardship should entail greater awareness of appropriate indications for OCS prescription, risk–benefits of OCS medications, side effects, effective add-on therapies and multidisciplinary review. If implemented, OCS stewardship can ensure that clinicians and patients with asthma are aware that OCS should not be used lightly, while providing reassurance that asthma can be controlled in most people without frequent use of OCS.

Background Telemedicine consultation can increase patients’ access to subspecialty care and decrease the number of unnecessary hospital transfers. In 2014, the Arkansas Hand Trauma Telemedicine Program (AHTTP) was established to extend specialized hand care throughout Arkansas. The purpose of this study is to assess whether transfers are affected when consultation with a hand specialist is performed by phone compared with using a live audiovisual consultation. Methods We reviewed data from the first year of the AHTTP. Data collection included type of consultation (telephone only or live audiovisual), need for transfer, and type of transfer (general orthopedic or hand specialist). Results In 2014, the first year of AHTTP there were 331 hand injuries identified; of those, 298 used the AHTTP with 195 (65%) using telemedicine and 103 (35%) using phone consultation only. The use of video when compared with phone consultation did not significantly affect the decision to transfer ( P = .42) or alter the rate of transfer for general orthopedic or hand specialist care ( P = .25). Conclusions The assessment of both phone and telemedicine modalities showed that there was no significant difference in transfer rates for either consultation, highlighting that communication with a hand surgeon was the key to accurate assessment of the need for transfer.

Greater attention is being paid to performance validity in patients with multiple sclerosis (MS), though limited work has examined symptom validity measures in this population. Extensive previous literature has examined the Structured Inventory of Malingered Symptomatology (SIMS) across diverse populations with variable results. The purpose of the present study was to determine the extent to which the SIMS and/or its associated variables/items are useful in detecting non-credible cognitive performance in patients with MS. Sixty-seven patients with MS (Mage = 48.64; 71.6% women; 83.6% White) were referred for neuropsychological evaluation within a large, Midwestern academic medical center. Participants were categorized into credible (n = 50) and non-credible (n = 17) groups based on standalone performance validity test (PVT) criteria. The non-credible group reported significantly higher SIMS total scores than the credible group (d = 1.69). Results revealed that SIMS total score was broadly elevated across the entire sample (M = 17.55, SD = 8.30) and significantly correlated with depressive (r = .56) and anxiety (r = .38) symptoms. Publisher-recommended cutoffs for SIMS total scores of > 14 (specificity = .50) and > 16 (specificity = .64) yielded unacceptable levels of false positives. A novel subscale (SIMS-MS) was created from six items that were endorsed by ≥ 25% of the non-credible group and ≤ 10% of the credible group. The SIMS-MS demonstrated good differentiability between groups (AUC = .87), with good sensitivity (.53) and excellent specificity (.96) at a cutoff of > 1 (i.e., ≥ 2), and it did not significantly correlate with depressive (r = .21) nor anxiety (r = .23) symptoms, suggesting appropriate discriminant validity from face valid psychiatric symptoms. The SIMS-MS showed preliminary clinical utility at identifying individuals with MS who demonstrate non-credible cognitive performance on standalone PVTs. Implications, limitations, and directions for further inquiry, including validation against other measures of both performance and symptom validity, were discussed.

This study examined the roles of microglia and monocytes in myelin destruction in patients with early multiple sclerosis (MS). Twenty-two cases were studied; the clinical duration was

Wound infections and sepsis are significant causes of morbidity after burn injury and can be alleviated by early excision and grafting. In situations that preclude early surgery, topical agents allow for a safer delay. Cerium nitrate compounded with silver sulfadiazine (Ce-SSD) is a burn cream that provides broad antibacterial activity, forms a temporary barrier, and promotes re-epithelialization. Methemoglobinemia is a rare, but oft-cited, systemic complication of Ce-SSD. In this retrospective review, 157 patients treated with Ce-SSD between July 2014 and July 2018 were identified, and the monitoring protocol for methemoglobinemia during Ce-SSD treatment was evaluated. The median age was 59 years (interquartile range [IQR], 47–70.5 years), with TBSA of 8.5% (IQR, 3–27), adjusted Baux score of 76 (IQR, 59–94), and inhalation injury present in 9.9% of patients. Primary endpoints included incidence of symptomatic and asymptomatic methemoglobinemia. Of the 9.6% (n = 15) of patients with methemoglobinemia, 73.3% (n = 11) had maximum methemoglobin levels ≥72 hours from the time of the first application. One patient developed clinically significant methemoglobinemia. Patients with TBSA ≥20% were more likely to develop methemoglobinemia (odds ratio 9.318, 95% confidence interval 2.078–65.73, P = .0078); however, neither Ce-SSD doses nor days of exposure were significant predictors. Ce-SSD application to temporize burn wounds until excision and grafting is safe, effective, and, in asymptomatic patients with TBSA

Hidradenitis suppurativa (HS) is a chronic, suppurative condition of the pilosebaceous unit. Patients suffering from HS demonstrate a molecular profile in keeping with a state of systemic inflammation and are often found to fit the criteria for a diagnosis of metabolic syndrome (MetS). In this paper, we review the literature with regards to established data on the prevalence of MetS in HS patients and revise the odds ratio of comorbid disease. Furthermore, we attempt to draw parallels between inflammatory pathways in HS and MetS and evaluate how convergences may explain the risk of comorbid disease, necessitating the need for multidisciplinary care.

Background Medication safety issues have detrimental implications on long-term outcomes in the high-risk kidney transplant (KTX) population. Medication errors, adverse drug events, and medication nonadherence are important and modifiable mechanisms of graft loss. Objective To describe the frequency and types of interventions made during a pharmacist-led, mobile health–based intervention in KTX recipients and the impact on patient risk levels. Methods This was a secondary analysis of data collected during a 12-month, parallel-arm, 1:1 randomized clinical controlled trial including 136 KTX recipients. Participants were randomized to receive either usual care or supplemental, pharmacist-driven medication therapy monitoring and management using a smartphone-enabled app integrated with telemonitoring of blood pressure and glucose (when applicable) and risk-based televisits. The primary outcome was pharmacist intervention type. Secondary outcomes included frequency of interventions and changes in risk levels. Results A total of 68 patients were randomized to the intervention and included in this analysis. The mean age at baseline was 50.2 years; 51.5% of participants were male, and 58.8% were black. Primary pharmacist intervention types were medication reconciliation and patient education, followed by medication changes. Medication reconciliation remained high throughout the study period, whereas education and medication changes trended downward. From baseline to month 12, we observed an approximately 15% decrease in high-risk patients and a corresponding 15% increase in medium- or low-risk patients. Conclusion and Relevance A pharmacist-led mHealth intervention may enhance opportunities for pharmacological and nonpharmacological interventions and mitigate risk levels in KTX recipients.

Background Coronary microvascular dysfunction (CMD) is associated with heart failure with preserved ejection fraction (HFpEF); however, pathophysiology is not well described. Hypothesis We hypothesized that CMD in women with suspected ischemia with no obstructive coronary artery disease (INOCA) is associated with cardiomyocyte dysfunction reflected by plasma levels of a cardiomyocyte calcium handling protein, cardiac bridge integrator 1 (cBIN1). Methods Women with suspected INOCA undergoing coronary function testing were included. Coronary flow reserve, vasodilation to nitroglycerin, change in coronary blood flow (ΔCBF), and vasodilation to acetylcholine (ΔAch) were evaluated. cBIN1 score (CS) levels in these women (n = 39) were compared to women with HFpEF (n = 20), heart failure with reduced ejection fraction (HFrEF) (n = 36), and reference controls (RC) (n = 50). Higher CS indicates cardiomyocyte tubule dysfunction. Results INOCA, HFpEF, and HFrEF women were older than RC (p

To analyze the effect on biochemical recurrence (BCR) of omitting PLND in subsequently upgraded/upstaged patients (pNx regret). Using nomograms, patients with low to intermediate-risk prostate cancer can be selected to omit a pelvic lymph node dissection (PLND) at the time of a radical prostatectomy (RP). However, some patients will experience upgraded pathology and/or stage.We searched a prospectively maintained single institution/multi-surgeon cohort of patients treated by RP and5-year follow-up. From 2006-2012, 1026 (521 pNx and 505 pN0/1) eligible patients with biopsy Gleason Score ≤3+4 and cT1c-cT2 undergoing RARP were included in the study.Gleason upgrading from ≤3+4 to3+4 and/or pT3-4 occurred in 17% of pNx and 32% of pN0/N1 (p0.001). BCR occurred in 5% of the pNx, and 7% of the PLND group. Five-year BCR free survival was higher in the pNx group (94.7% vs. 91%, P = .048). BCR occurred in 3% in the non-pNx regret and 18% in the pNx regret patients. However, with propensity score matching with pNx regret and pN0/N1 patients, 5-year BCR free survival rates were similar (81% vs 77%, P = .466).Low to favorable intermediate-risk patients who PLND was omitted and experienced upgrading or upstaging (pNx regret), have a higher predicted BCR. However, when matched to a similar cohort with pN0/N1, the BCR did not differ. Omission of a PLND does not appear to alter the rates of BCR compared to PLND inclusion.