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Objective Genetically engineered pigs are thought to be an alternative organ source for patients in end-stage heart failure unable to receive a timely allograft. However, cardiac xenografts exhibit growth and diastolic heart failure within 1 month after transplantation. Grafts function for up to 6 months, but only after administration of temsirolimus and afterload-reducing agents to reduce this growth. In this study we investigated the growth and hemodynamics of growth hormone receptor (GHR) knockout xenografts, without the use of adjuncts to prevent intrinsic graft growth after transplantation. Methods Genetically engineered pig hearts were transplanted orthotopically into weight-matched baboons between 15 and 30 kg, using continuous perfusion preservation before implantation (n = 5). Xenografts included knockout of carbohydrate antigens and knockin of human transgenes for thromboregulation, complement regulation, and inflammation reduction (grafts with intact growth hormone, n = 2). Three grafts contained the additional knockout of GHR (GHR knockout grafts; n = 3). Transthoracic echocardiograms were obtained twice monthly and comprehensively analyzed by a blinded cardiologist. Hemodynamics were measured longitudinally after transplantation. Results All xenografts demonstrated life-supporting function after transplantation. There was no difference in intrinsic growth, measured using septal and posterior wall thickness and left ventricular mass, on transthoracic echocardiogram out to 1 month in either GHR knockout or GHR intact grafts. However, hypertrophy of the septal and posterior wall was markedly elevated by 2 months post transplantation. There was minimal hypertrophy out to 6 months in GHR knockout grafts. Physiologic mismatch was present in all grafts after transplantation, which is largely independent of growth. Conclusions Xenografts with GHR knockout show reduced post-transplantation xenograft growth using echocardiography >6 months after transplantation, without the need for other adjuncts.

Background:Evidence from pandemics suggests that influenza is often associated with bacterial coinfection. Among patients hospitalized for influenza pneumonia, we report the rate of coinfection and distribution of pathogens, and we compare outcomes of patients with and without bacterial coinfection.Methods:We included adults admitted with community-acquired pneumonia (CAP) and tested for influenza from 2010 to 2015 at 179 US hospitals participating in the Premier database. Pneumonia was identified using an International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) algorithm. We used multiple logistic and gamma-generalized linear mixed models to assess the relationships between coinfection and inpatient mortality, intensive care unit (ICU) admission, length of stay, and cost.Results:Among 38,665 patients hospitalized with CAP and tested for influenza, 4,313 (11.2%) were positive. In the first 3 hospital days, patients with influenza were less likely than those without to have a positive culture (10.3% vs 16.2%; P < .001), and cultures were more likely to contain Staphylococcus aureus (34.2% vs 28.2%; P = .007) and less likely to contain Streptococcus pneumoniae (24.9% vs 31.0%; P = .008). Of S. aureus isolates, 42.8% were methicillin resistant among influenza patients versus 53.2% among those without influenza (P = .01). After hospital day 3, pathogens for both groups were similar. Bacterial coinfection was associated with increased odds of in-hospital mortality (aOR, 3.00; 95% CI, 2.17–4.16), late ICU transfer (aOR, 2.83; 95% CI, 1.98–4.04), and higher cost (risk-adjusted mean multiplier, 1.77; 95% CI, 1.59–1.96).Conclusions:In a large US inpatient sample hospitalized with influenza and CAP, S. aureus was the most frequent cause of bacterial coinfection. Coinfection was associated with worse outcomes and higher costs.

On a population basis multiple nutrient deficiencies are common in developing countries, whereas in developed countries obesity and vitamin D deficiency are important health issues. While nutrient deficiencies can lead to disease, the results of clinical trials investigating the influence of supplementing various nutrients such as essential fatty acids, iron, and vitamin A on upper respiratory disease have been mixed. Probiotics may have a role in the treatment of upper respiratory disease, but appropriate probiotic strain/strains, supplement timing, as well as the dosage and method of administration continue to be debated. In clinical practice, many patients report that a milk exclusion diet is beneficial in reducing respiratory mucus production; however, the scientific basis for this remains controversial. Increasing evidence indicates that zinc supplementation is beneficial in the management of upper respiratory infections. A number of clinical trials also indicate that vitamin D supplementation has a potential role in the prevention of upper respiratory disease. Optimal vitamin D levels and dosages remain to be determined.

This study assessed the psychological predictors of preferences for return of comprehensive tumor genomic profiling (CTGP) results in patients with advanced cancers, enrolled in the Molecular Screening and Therapeutics Program. Patients completed a questionnaire prior to undergoing CTGP. Of the 1434 who completed a questionnaire, 96% would like to receive results that can guide treatment for their cancer, and preference for receiving this type of result was associated with lower tolerance of uncertainty. Sixty-four percent would like to receive results that cannot guide treatment, and lower tolerance of uncertainty, self-efficacy, and perceived importance were associated with this preference. Fifty-nine percent would like to receive variants of unknown significance, which was associated with lower tolerance of uncertainty, higher self-efficacy, and perceived importance. Eighty-six percent wanted to receive germline results that could inform family risk. This was associated with higher self-efficacy, perceived importance, and perceived susceptibility. Although most patients wanted to receive all types of results, given the differing patient preferences regarding the return of results depending on the utility of the different types of results, it appears critical to safeguard patient understanding of result utility to achieve informed patient choices. This should be accompanied by appropriate consent processes.

Objectives The COMMENCE trial was conducted to evaluate the safety and effectiveness of an aortic bioprosthesis with novel RESILIA tissue (Edwards Lifesciences, Irvine, Calif). Reports of early noncalcific valve failure resulting from thrombosis or leaflet tears in other valves warrant careful evaluation of early valve performance. Methods Patients underwent clinically indicated surgical aortic valve replacement with the Edwards Pericardial Aortic Bioprosthesis, Model 11000A (Edwards Lifesciences) in a prospective, multinational, multicenter (n = 27), single-arm, Food and Drug Administration Investigational Device Exemption trial. Events were adjudicated by an independent clinical events committee; echocardiograms were analyzed by an independent core laboratory. Results Between January 2013 and March 2016, 689 patients received the study valve. Mean age was 67.0 ± 11.6 years. Mean Society of Thoracic Surgeons predicted risk of mortality was 2.0% ± 1.8%. Follow-up duration was 3.7 ± 1.2 years, with a total of 2533 patient years of follow-up and a median follow-up of 4 years. Early all-cause mortality was 1.2%, thromboembolism 2.3%, all bleeding 1.0%, and major paravalvular leak 0.1%. One- and 4-year actuarial freedom from all-cause mortality was 97.7% (95% confidence interval, 96.5%-98.8%) and 91.9% (95% confidence interval, 89.7%-94.1%), respectively. At 4 years, New York Heart Association functional class improved compared with baseline in 63.0%, effective orifice area was 1.5 ± 0.5 cm2, and mean gradient was 11.0 ± 5.6 mm Hg. Freedom from moderate or greater transvalvular insufficiency was 99.7%. There were no events of structural valve deterioration. Conclusions Safety and hemodynamic performance of this aortic bioprosthesis with RESILIA tissue at 4 years are favorable. This novel tissue does not appear to result in unexpected early thrombosis events or noncalcific structural valve deterioration.

The COVID-19 pandemic of 2020 imposed significant strain on critical care services worldwide. The South London region experienced the largest numbers of critical care admissions in the United Kingdom with King’s College Hospital one of the busiest centres. This article outlines, using a descriptive narrative, the significant changes that occurred within King’s Critical Care as a result of the pandemic and the decisions that were taken to provide effective co-ordination and control to the expanded service, in part drawing on the military experience of two of the authors. The wider context of crisis and major incident leadership and management is also discussed contrasting different approaches used in civilian and military settings.

Walking is a common activity among older adults. However, the effects of walking on health-related outcomes in people with low bone mineral density (BMD) are unknown. The authors included randomized controlled trials comparing walking to control in individuals aged ≥50 years with low BMD and at risk of fractures. The authors identified 13 randomized controlled trials: nine multicomponent interventions including walking, one that was walking only, and three Nordic walking trials. Most studies had a high risk of bias. Nordic walking may improve the Timed Up-and-Go values (1.39 s, 95% CI [1.00, 1.78], very low certainty). Multicomponent interventions including walking improved the 6-min walk test (39.37 m, 95% CI [21.83, 56.91], very low certainty) and lumbar spine BMD (0.01 g/cm2, 95% CI [0.00, 0.03], low certainty evidence). The effects on quality of life or femoral neck BMD were not significant. There were insufficient data on fractures, falls, or mortality. Nordic walking may improve physical functioning. The effects on other outcomes are less certain; one may need to combine walking with other exercises to be of benefit.

Left ventricular assist devices (LVADs) have been increasingly used as a therapy for patients with end-stage heart failure. However, a growing number of clinical observations have shown that LVADs are associated with thromboembolic events, which are potentially related to the changes in intraventricular flow. Particularly, the flow fields around the inflow cannula (IC) of the LVAD. In this study, a fluid structure interaction (FSI) simulation was conducted to evaluate the hemodynamics of a patient specific left ventricle (LV) with varying LVAD IC orientations. The LV model was obtained from computed tomography scans and modeled to have contraction and relaxation during cardiac cycles following available experimental data of LV volume changes. The LV of the patient was assumed to have an end systolic volume of 223.7 mL and a stroke volume of 46.4 mL. Four different IC positions were considered: towards the (1) septum; (2) aortic valve (AV); (3) mitral valve (MV) and (4) inferior wall (IW). The potential thrombus growth around the IC was assumed to be caused by blood stagnation regions with low velocity (

Blood pumps have been increasingly used in mechanically assisted circulation for ventricular assistance and extracorporeal membrane oxygenation support or during cardiopulmonary bypass for cardiac surgery. However, there have always been common complications such as thrombosis, hemolysis, bleeding, and infection associated with current blood pumps in patients. The development of more biocompatible blood pumps still prevails during the past decades. As one of those newly developed pumps, the Breethe pump is a novel extracorporeal centrifugal blood pump with a hybrid magnetic and mechanical bearing with attempt to reduce device-induced blood trauma. To characterize the hydrodynamic and hemolytic performances of this novel pump and demonstrate its superior biocompatibility, we use a combined computational and experimental approach to compare the Breethe pump with the CentriMag and Rotaflow pumps in terms of flow features and hemolysis under an operating condition relevant to ECMO support (flow: 5 L/min, pressure head: ~350 mmHg). The computational results showed that the Breethe pump has a smaller area-averaged wall shear stress (WSS), a smaller volume with a scalar shear stress (SSS) level greater than 100 Pa and a lower device-generated hemolysis index compared to the CentriMag and Rotaflow pumps. The comparison of the calculated residence times among the three pumps indicated that the Breethe pump might have better washout. The experimental data from the in vitro hemolysis testing demonstrated that the Breethe pump has the lowest normalized hemolysis index (NIH) than the CentriMag and Rotaflow pumps. It can be concluded based on both the computational and experimental data that the Breethe pump is a viable pump for clinical use and it has better biocompatibility compared to the clinically accepted pumps.

BACKGROUND: Surgical resection is an integral component of the curative-intent treatment for most patients with non-metastatic rectal cancer. However, some patients refuse surgery for a number of reasons. Utilizing the National Cancer Database (NCDB), we investigated the sociodemographic and clinical factors associated with patients who were coded as having been offered but refused surgery, and the factors affecting overall survival (OS) in these patients. METHODS: Adult patients with adenocarcinoma of the rectum (excluding T1N0M0 and M1 disease) diagnosed from 2004 to 2015 were analyzed in this retrospective cohort study. Logistic regression was performed to identify factors associated with refusal of surgery. OS of patients refusing surgery was compared using Kaplan-Meier estimate, log-rank test, propensity score matching, and proportional hazards regression. RESULTS: A total of 55,704 patients were identified: 54,266 received definitive surgery (97.4%) and 1,438 refused (2.6%). Of patients refusing surgery, 135 (9.4%) were stage I, 709 (49.3%) were stage II, and 594 (41.3%) were stage III. Patients were more likely to refuse surgery as the study period progressed (P

Background and aims Extrahepatic portal vein occlusion (EHPVO) from portal vein thrombosis is a rare condition associated with substantial morbidity and mortality. The purpose of this study is to investigate the efficacy of transjugular intrahepatic portosystemic shunts (TIPS) for the treatment of chronic EHPVO, cavernomatosis, and mesenteric venous thrombosis in adults without cirrhosis who are refractory to standard-of-care therapy. Approach and results Thirty-nine patients with chronic EHPVO received TIPS. Laboratory parameters and follow-up were assessed at 1, 3, 6, 12, and 24 months, and every 6 months thereafter. Two hepatologists adjudicated symptom improvement attributable to mesenteric thrombosis and EHPVO before/after TIPS. Kaplan-Meier was used to assess primary and overall TIPS patency, assessing procedural success. Adverse events, radiation exposure, hospital length-of-stay and patency were recorded. Cavernoma was present in 100%, with TIPS being successful in all cases using splenic, mesenteric, and transhepatic approaches. Symptom improvement was noted in 26 of 30 (87%) at 6-month follow-up. Twelve patients (31%) experienced TIPS thrombosis. There were no significant long-term laboratory adverse events or deaths. At 36 months, freedom from primary TIPS thrombosis was 63%; following secondary interventions, overall patency was increased to 81%. Conclusions TIPS in chronic, noncirrhotic EHPVO with cavernomas and mesenteric venous thrombosis is technically feasible and does not adversely affect liver function. Most patients demonstrate subjective and objective benefit from TIPS. Improvement in patency rates are needed with proper timing of adjuvant anticoagulation.

BACKGROUND The purpose of the present study was to evaluate associations between changes in segmental vertebral coronal angulation (screw angulation) and overall height after anterior spinal growth tethering for the treatment of idiopathic scoliosis and to compare the rates of coronal angulation change using the preoperative Sanders stage. METHODS Patients with idiopathic scoliosis who underwent anterior spinal growth tethering between 2012 and 2016 and had ≥2 years of follow-up were retrospectively studied. We calculated each segment's screw angulation rate of change (degrees/month) and each patient's height velocity (cm/month) between each of the visits (3 to 12 visits/patient) and divided the visits into 4 groups by postoperative duration ( 2 to 3 years, >3 years). Patients were divided into 2 groups according to the preoperative Sanders stage. Generalized estimating equations and repeated-measures correlation were utilized for analyses with non-independent samples. RESULTS We analyzed 23 patients (16 female, 7 male) with a mean age (and standard deviation) of 12.2 ± 1.6 years who had right thoracic idiopathic scoliosis (mean, 53° ± 8°). All patients were immature at the time of surgery (Risser stage 0 or 1, Sanders stage 2 or 3). The mean duration of follow-up was 3.4 ± 1.1 years (range, 2 to 5 years). The rate of change for each segment's screw angulation after anterior spinal growth tethering was -0.16°, -0.14°, -0.05°, and 0.03° per month (with negative values indicating a reduction in scoliosis) for 2 to 3 years, and >3 years, respectively (p ≤ 0.001), and the mean height velocity was 0.65, 0.57, 0.30, and 0.19 cm per month for 2 to 3 years, and >3 years, respectively (p < 0.001). Changes in screw angulation correlated with height increases after anterior spinal growth tethering (r = -0.46, p < 0.001). Scoliosis correction for patients in the Sanders stage-2 group continued for 3 years (0.23°, 0.23°, and 0.09° per level per month for the first 3 years, respectively) and occurred at more than twice the rate for patients in the Sanders stage-3 group, for whom scoliosis correction ceased 2 years postoperatively (0.11° and 0.09° per level per month for the first 2 years, respectively). CONCLUSIONS Scoliosis correction was associated with overall height changes and occurred primarily within 2 to 3 years after surgery in this cohort of largely Risser stage-0 patients. The correction rate was 2.8° per segment per year for the first 2 years in the Sanders stage-2 group, compared with 1.2° per segment per year for the Sanders stage-3 group. Surgical timing that considers the patient's skeletal maturity is an important factor in generating proper postoperative correction after anterior spinal growth tethering. LEVEL OF EVIDENCE Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Introduction Advances in transjugular intrahepatic portosystemic shunt (TIPS) technology have led to expanded use. We sought to characterize contemporary outcomes of TIPS by common indications. Methods This was a multicenter, retrospective cohort study using data from the Advancing Liver Therapeutic Approaches study group among adults with cirrhosis who underwent TIPS for ascites/hepatic hydrothorax (ascites/HH) or variceal bleeding (2010-2015). Adjusted competing risk analysis was used to assess post-TIPS mortality or liver transplantation (LT). Results Among 1,129 TIPS recipients, 58% received TIPS for ascites/HH and 42% for variceal bleeding. In patients who underwent TIPS for ascites/HH, the subdistribution hazard ratio (sHR) for death was similar across all Model for End-Stage Liver Disease Sodium (MELD-Na) categories with an increasing sHR with rising MELD-Na. In patients with TIPS for variceal bleeding, MELD-Na ≥20 was associated with increased hazard for death, whereas MELD-Na ≥22 was associated with LT. In a multivariate analysis, serum creatinine was most significantly associated with death (sHR 1.2 per mg/dL, 95% confidence interval [CI] 1.04-1.4 and 1.37, 95% CI 1.08-1.73 in ascites/HH and variceal bleeding, respectively). Bilirubin and international normalized ratio were most associated with LT in ascites/HH (sHR 1.23, 95% CI 1.15-1.3; sHR 2.99, 95% CI 1.76-5.1, respectively) compared with only bilirubin in variceal bleeding (sHR 1.06, 95% CI 1.00-1.13). Discussion MELD-Na has differing relationships with patient outcomes dependent on TIPS indication. These data provide new insights into contemporary predictors of outcomes after TIPS.

Fear of cancer recurrence/occurrence (FCR/O) is prevalent and associated with poorer psychological outcomes but can also motivate individuals to pursue genomic information about cancer risk. Guided by Protection Motivation Theory, this study investigated FCR/O prevalence and associated factors among probands previously diagnosed with a cancer of likely heritable origin, and their relatives, who had agreed to have germline genome sequencing. Three hundred and forty-eight probands and 167 relatives completed the Concerns about Recurrence Questionnaire (adapted for occurrence for some relatives) within 1 month of agreeing to undertake genome sequencing. Linear regressions investigated demographic, disease, attitude and behavioral associations with FCR/O. Probands demonstrated greater FCR compared to relatives. In probands, greater FCR was associated with being female, non-English speaking at home, less time since diagnosis, greater intention to change behavior if gene variant found, lower perceived ability to cope with results, higher perceived susceptibility to having a recurrence, and more negative attitudes towards uncertainty. For relatives with cancer, greater FCR was associated with being male, greater intention to change behavior if a gene variant found, and higher perceived susceptibility to recurrence. In relatives without cancer, greater FCO was associated with not having had genetic testing prior to this study, lower perceived ability to cope with results, and higher perceived susceptibility to developing cancer. Current findings on FCR/O prevalence and associated demographic and attitudinal variables in those who pursue genomic risk information might be used to target interventions that can prevent adverse psychological outcomes in vulnerable patients.

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) for refractory cardiac arrest has improved mortality in post-cardiac surgery patients; however, loss of neurologic function remains one of the main and devastating complications. We reviewed our experience with ECPR and investigated the effect of cannulation strategy on neurologic outcome in adult patients who experienced cardiac arrest following cardiac surgery that was managed with ECPR. Methods: Patients were categorized by central versus percutaneous peripheral VA-extracorporeal membrane oxygenation (ECMO) cannulation strategy. We reviewed patient records and evaluated in-hospital mortality, cause of death, and neurologic status 72 hours after cannulation. Results: From January 2010 to September 2019, 44 patients underwent post-cardiac surgery ECPR for cardiac arrest. Twenty-six patients received central cannulation; 18 patients received peripheral cannulation. Mean post-operative day of the cardiac arrest was 3 and 9 days (p = 0.006), and mean time between initiation of CPR and ECMO was 40 ± 24 and 28 ± 22 minutes for central and peripheral cannulation, respectively. After 72 hours of VA-ECMO support, 30% of centrally cannulated patients versus 72% of peripherally cannulated patients attained cerebral performance status 1–2 (p = 0.01). Anoxic brain injury was the cause of death in 26.9% of centrally cannulated and 11.1% of peripherally cannulated patients. Survival to discharge was 31% and 39% for central and peripheral cannulation, respectively. Conclusions: Peripheral VA-ECMO allows for continuous CPR and systemic perfusion while obtaining vascular access. Compared to central cannulation, a peripheral cannulation strategy is associated with improved neurologic outcomes and decreased likelihood of anoxic brain death.

For patients diagnosed with a rare musculoskeletal or neuromuscular disease, pain may transition from acute to chronic; the latter yielding additional challenges for both patients and care providers. We assessed the present understanding of pain across a set of ten rare, noninfectious, noncancerous disorders; Osteogenesis Imperfecta, Ehlers-Danlos Syndrome, Achondroplasia, Fibrodysplasia Ossificans Progressiva, Fibrous Dysplasia/McCune-Albright Syndrome, Complex Regional Pain Syndrome, Duchenne Muscular Dystrophy, Infantile- and Late-Onset Pompe disease, Charcot-Marie-Tooth Disease, and Amyotrophic Lateral Sclerosis. Through the integration of natural history, cross-sectional, retrospective, clinical trials, & case studies we described pathologic and genetic factors, pain sources, phenotypes, and lastly, existing therapeutic approaches. We highlight that while rare diseases possess distinct core pathologic features, there are a number of shared pain phenotypes and mechanisms that may be prospectively examined and therapeutically targeted in a parallel manner. Finally, we describe clinical and research approaches that may facilitate more accurate diagnosis, monitoring, and treatment of pain as well as elucidation of the evolving nature of pain phenotypes in rare musculoskeletal or neuromuscular illnesses.

Background This study compares outcomes of conventional and less-invasive (LI) approaches for aortic valve replacement (AVR) using The Society of Thoracic Surgeons database. Methods Between 2011 and 2017, we identified 122,474 patients undergoing isolated primary AVR. Patients were categorized into 3 groups: (1) full sternotomy (FS) (n = 98,549; 78%), (2) partial sternotomy (PS) (n = 17,306; 15%), and (3) right thoracotomy (RT) (n = 6619; 7%). Results The rate of LI-AVR increased from 17% in 2011 to 23% in 2016 (P Conclusions Less-invasive AVR is associated with an operative mortality and postoperative stroke rate similar to that of FS. Less-invasive AVRs should serve as a benchmark for comparison between transcatheter aortic valve replacement and surgical AVR in low-risk patients.

Currarino syndrome (CS) is an autosomal dominant syndrome caused by mutations in MNX1 and characterized by anorectal abnormalities, partial sacral agenesis, and presacral masses. The presacral masses are typically benign; however, malignant degeneration can occur, and presacral neuroendocrine tumors (NETs) have been reported in six cases. We report three individuals from two families affected by CS in which multiple individuals developed presacral NETs. The first family, 491, had six members with features of CS, including two siblings who presented with presacral, Grade 2 NETs, one of which had metastasized to bone and lymph nodes. A germline c.874C>T (p.Arg292Trp) mutation was found in a highly conserved region of MNX1 in three affected members who underwent sequencing. A second somatic variant/deletion in MNX1 was not detected in either patient's tumor. In the second family, 342, the proband presented with an incidentally discovered presacral NET. The proband's father had previously undergone resection of a presacral NET, and so genetic testing was performed, which did not reveal an MNX1 mutation or copy number variants. The lack of a second, somatic mutation in the tumors from family 491 argues against MNX1 acting as a tumor suppressor, and the absence of a germline MNX1 mutation in family 342 suggests that other genetic and anatomic factors contribute to the development of presacral NETs. These cases highlight the variable presentation of CS, and the potential for malignancy in these patients.

To evaluate associations between vertebrae and disc shape asymmetry and adolescent idiopathic scoliosis (AIS) curve severity. Analysis included normal screening referrals and patients with right, main thoracic AIS who underwent upright, biplanar radiographs with 3D reconstruction at a single institution from 2010 to 2015. Peri-apical anterior, posterior, right, and left vertebral body heights (aVBH, pVBH, rVBH, lVBH) and intervertebral disc heights (DH) were measured, and ratios of these measurements were calculated in sagittal and coronal planes. Correlations were performed between curve severity and height measurements. Sagittal and coronal plane components of these measurements were compared between normal controls with coronal curve measurements

BACKGROUND Anorectal melanoma (ARM) is a rare disease with a poor prognosis. Evidence on optimal treatment is limited and surgical management varies widely. We hypothesized that the frequency of abdominoperineal resection used as primary treatment of ARM has decreased over the past several decades. AIM To update our understanding of outcomes for patients with ARM and analyze management trends around the world. METHODS This is a multi-institutional, retrospective study of patients treated for ARM at 7 hospitals. Hospitals included both large, academic, tertiary care centers and smaller, general community hospitals. Using prospectively maintained institutional tumor registries, we identified 24 patients diagnosed with ARM between January 2000 and May 2019. We analyzed factors prognostic for recurrence and survival. We then used Cox regression to measure overall survival (OS) and melanoma-specific survival. We also performed a literature review to assess trends in surgical management and outcomes. RESULTS Of the 24 patients diagnosed with ARM, 12 (50.0%) had local, 8 (33.3%) regional, and 4 (16.7%) distant disease at diagnosis. Median time to recurrence was 10.4 mo [interquartile range (IQR) 7.5-17.2] with only 2 patients (9.3%) not developing recurrence following surgical resection. Median OS was 18.8 mo (IQR 13.5-33.9). One patient is still alive without recurrence at 21.4 mo from diagnosis; no other patient survived 5 years. Primary surgical management with abdominoperineal resection (APR) vs wide excision (WE) did not lead to differences in OS [hazard ratio = 1.4 (95%CI: 0.3-6.8)]. Review of the literature revealed geographic differences in surgical management of ARM, with increased use of WE in the United States and Europe over time and more frequent use of APR in Asia and India. There was no significant improvement in survival over time. CONCLUSION There is wide variation in the management of ARM and survival outcomes remain poor regardless of approach. Surgical management should aim to minimize morbidity.

A beneficial cocktail Since the start of the coronavirus disease 2019 (COVID-19) pandemic, considerable effort has gone into generating and characterizing neutralizing antibodies that could be used as therapeutics. Studies in humanized mice and convalescent humans led to the development of a cocktail of two potent antibodies that simultaneously bind to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and prevent the virus from entering host cells. Baum et al. evaluated the efficacy of this cocktail, REGN-COV2, in rhesus macaques, which may model mild disease, and in golden hamsters, which present more severe symptoms. The antibody cocktail provided benefits in both models when administered either prophylactically or therapeutically and is currently in clinical trials. Science, this issue p. 1110, In vivo efficacy of the REGN-COV2 antibody cocktail is evaluated in the rhesus macaque and golden hamster models of SARS-CoV-2 infection., An urgent global quest for effective therapies to prevent and treat coronavirus disease 2019 (COVID-19) is ongoing. We previously described REGN-COV2, a cocktail of two potent neutralizing antibodies (REGN10987 and REGN10933) that targets nonoverlapping epitopes on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. In this report, we evaluate the in vivo efficacy of this antibody cocktail in both rhesus macaques, which may model mild disease, and golden hamsters, which may model more severe disease. We demonstrate that REGN-COV-2 can greatly reduce virus load in the lower and upper airways and decrease virus-induced pathological sequelae when administered prophylactically or therapeutically in rhesus macaques. Similarly, administration in hamsters limits weight loss and decreases lung titers and evidence of pneumonia in the lungs. Our results provide evidence of the therapeutic potential of this antibody cocktail.

To evaluate how 3D parameters of the instrumented thoracic spine relate to the uninstrumented lumbar spine following thoracic-only fusion (TOF) for adolescent idiopathic scoliosis (AIS) and determine the factors predictive of lumbar correction. A multi-center retrospective review was conducted of AIS patients with Lenke 1–4 B or C curves undergoing fusion of their thoracic spine only with minimum 2-year follow-up and 3D spine reconstructions from biplanar radiography. Pre-operative to 2-year post-operative differences were evaluated. Pearson’s correlations were used to identify 3D coronal, sagittal and axial relationships at 2 years post-operative. Multivariate linear regression was used to identify variables most predictive of lumbar curve correction. Eighty-four AIS patients met inclusion (54 B modifiers, 30 C modifiers). Average pre-operative thoracic and lumbar curves were 54 ± 9° and 41 ± 7° and corrected to 19 ± 7° and 21 ± 7°, respectively. 3D T5-T12 thoracic kyphosis increased from 6 ± 13° to 26 ± 8°. Thoracic and lumbar apical rotation decreased from − 14 ± 6° to -5 ± 6° and 13 ± 5° to 11 ± 6°, respectively. Thoracic curve correction correlated with lumbar curve correction (r = 0.67, p = 0.001) and decreased LIV tilt correlated with smaller residual lumbar curve magnitude (r = 0.63, p

BACKGROUND AND AIMS Radioembolization (yttrium-90 [Y90]) is used in hepatocellular carcinoma (HCC) as a bridging as well as downstaging liver-directed therapy to curative liver transplantation (LT). In this study, we report long-term outcomes of LT for patients with HCC who were bridged/downstaged by Y90. APPROACH AND RESULTS Patients undergoing LT following Y90 between 2004 and 2018 were included, with staging by United Network for Organ Sharing (UNOS) tumor-node-metastasis criteria at baseline pre-Y90 and pre-LT. Post-Y90 toxicities were recorded. Histopathological data of HCC at explant were recorded. Long-term outcomes, including overall survival (OS), recurrence-free survival (RFS), disease-specific mortality (DSM), and time-to-recurrence, were reported. Time-to-endpoint analyses were estimated using Kaplan-Meier. Univariate and multivariate analyses were performed using a log-rank test and Cox proportional-hazards model, respectively. During the 15-year period, 207 patients underwent LT after Y90. OS from LT was 12.5 years, with a median time to LT of 7.5 months [interquartile range, 4.4-10.3]. A total of 169 patients were bridged, whereas 38 were downstaged to LT. Respectively, 94 (45%), 60 (29%), and 53 (26%) patients showed complete, extensive, and partial tumor necrosis on histopathology. Three-year, 5-year, and 10-year OS rates were 84%, 77%, and 60%, respectively. Twenty-four patients developed recurrence, with a median RFS of 120 (95% confidence interval, 69-150) months. DSM at 3, 5, and 10 years was 6%, 11%, and 16%, respectively. There were no differences in OS/RFS for patients who were bridged or downstaged. RFS was higher in patients with complete/extensive versus partial tumor necrosis (P

Objective To describe the technique and outcomes of mesenteric access under ultrasound guidance to perform portal vein recanalization–transjugular intrahepatic portosystemic shunt (PVR-TIPS). Methods Four patients (3 male: 1 female, mean age: 46.2 years; range 38–64 years) with portal vein thrombosis (PVT) and cavernous transformation were eligible for PVR-TIPS. Due to inaccessible splenic vein (one patient with history of splenectomy and 3 patients with unavailable splenic vein during the procedure), noninvasive direct puncture of superior (n = 3) and inferior (n = 1) mesenteric vein was conducted under ultrasound guidance to obtain access for PVR-TIPS. Results Trans-mesenteric access and PVR-TIPS were successful in all patients at first attempt. No immediate complication was observed following the procedures. Follow-up imaging with computed tomography (CT) scan and Doppler ultrasound revealed patent TIPS and portal venous vasculature in all patients. Conclusion Percutaneous noninvasive transmesenteric access is a feasible approach for PVR-TIPS in patients with inaccessible splenic veins. Level of evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. Electronic supplementary material The online version of this article (10.1007/s00270-020-02713-0) contains supplementary material, which is available to authorized users.

Identifying the mechanisms through which genetic risk causes dementia is an imperative for new therapeutic development. Here, we apply a multistage, systems biology approach to elucidate the disease mechanisms in frontotemporal dementia. We identify two gene coexpression modules that are preserved in mice harboring mutations in MAPT, GRN and other dementia mutations on diverse genetic backgrounds. We bridge the species divide via integration with proteomic and transcriptomic data from the human brain to identify evolutionarily conserved, disease-relevant networks. We find that overexpression of miR-203, a hub of a putative regulatory microRNA (miRNA) module, recapitulates mRNA coexpression patterns associated with disease state and induces neuronal cell death, establishing this miRNA as a regulator of neurodegeneration. Using a database of drug-mediated gene expression changes, we identify small molecules that can normalize the disease-associated modules and validate this experimentally. Our results highlight the utility of an integrative, cross-species network approach to drug discovery.

To characterize the relationship between objective tympanogram values and patient-reported symptoms and associations with common comorbid conditions.Cross-sectional study with prospective data collection.Tertiary medical center.Patients undergoing routine audiometric evaluation between October 2018 and June 2019 were included. Participants with temporomandibular joint dysfunction, inner ear hydrops, and similar conditions were excluded. Symptoms were assessed with the 7-item Eustachian Tube Dysfunction Questionnaire. Demographics and medical comorbidities were recorded from the medical record. Analysis of tympanometric peak pressure (TPP), demographics, and comorbidities was performed to determine associations with clinically significant eustachian tube dysfunction (ETD) symptoms.A total of 250 patients were included with similar demographics: 101 (40.4%) in the asymptomatic group and 149 (59.6%) in the symptomatic group. The median (interquartile range) TPP was -10 (20) daPa and -25 (100) daPa in the asymptomatic and symptomatic groups, respectively. A diagnosis of rhinitis was more likely to be associated with significant ETD symptoms (adjusted odds ratio, 2.61; 95% CI, 1.23-5.63). A subgroup analysis revealed that symptomatic patients with normal TPP values were negatively skewed as compared with asymptomatic patients. This symptomatic group had a higher prevalence of rhinitis and chronic rhinosinusitis than the asymptomatic group.Patients with symptoms of ETD may have a TPP within a range typically considered normal per conventional standards. This suggests that the currently accepted interpretation of tympanometry findings may be insensitive for the diagnosis of less severe cases of ETD.

In this article, we present a variety of measures that quantify equity in cancer mortality outcomes, demonstrate how the measures perform with various cancer types, and identify counties, or “bright spots,” that meet the criteria of those measures. Using county-level age-adjusted mortality rates for 2007–2016 from the National Center for Health Statistics, we identified counties that had both equitable and optimal outcomes for Black and White death rates across 5 types of cancer: cancers of the lung/bronchus, prostate, female breast, colorectum, and liver. The number of counties that met the criteria ranged from 0 to 442, depending on cancer type and measure used. Prostate cancer and male liver cancer consistently had the lowest number of “bright spots,” with a maximum of 3 counties meeting the most lenient criteria. This paper presents several ways to examine equity, using rate ratios and standard error measures, in cancer mortality outcomes. It highlights areas with positive progress toward equity and areas with a potential need for equity-focused cancer-control planning. Examining local areas of positive deviance can inform cancer-control programming and planning around health equity.

Lyme disease (LD) is the most common tick-borne illness in Europe. Population-based studies in European children are few. This study aimed to assess the incidence, clinical presentation, treatment and outcome of serologically confirmed paediatric LD in the Republic of Ireland over a 5-year period. A retrospective review of records from accredited laboratories performing Borrelia burgdorferi serological testing was undertaken. Proformas were distributed to clinicians of children and adolescents with positive Lyme serology. Data were requested regarding clinical presentation, treatment and outcome. Updated NICE guidelines were used to classify clinical cases. Serology testing for B. burgdorferi was performed on 2908 samples. Sixty-three (2.2%) children were two-tier positive, generating a crude annual incidence rate of 1.15/100,000. Proformas were returned for 55 (87%) and 47 met clinical and laboratory criteria for LD. Twenty-seven (57%) presented with non-focal symptoms (erythema migrans and/or influenza-like symptoms), and 20 (43%) with focal symptoms (cranial nerve involvement, 11; CNS involvement, 8; arthritis, 1). Median age at presentation was 8.2 (2.5-17.9) years. Seventeen (36%) acquired LD overseas. Twenty-five (83%) of the remaining 30 children acquired infection in the West/Northwest of Ireland. Full resolution of symptoms was reported in 97% of those with available data. Serologically confirmed LD in children is relatively rare in the Republic of Ireland. Ninety-eight percent of children tested were seronegative. Of the seropositive cases, 40% could have been diagnosed based on clinical findings alone. Neurological presentations (40%) were common. Full resolution of symptoms occurred in almost all (97%) where data were available.

Objective To perform a pilot study of short-term safety, tolerability, and impact on urinary stone risk parameters of the vasopressin V2-receptor antagonist tolvaptan (which increases urinary excretion of free water) among adolescents and young adults with cystinuria. Materials and Methods We enrolled cystinuria patients age 12-25 years. Subjects were treated for 4 days at low-dose tolvaptan (0.3 mg/kg/day, maximum 30 mg) and 4 days at high dose (0.6 mg/kg/day, maximum 60 mg). Twenty-four-hour urine collections were done at baseline, day 3-4 of the dosing period, day 7-8 of the dosing period, and 3-6 days after washout. Primary outcome was cystine capacity (mg/L, target capacity > 0). Secondary outcomes included other urinary/serum parameters, tolerability, and thirst response. Results Two females (17, 23 years) and 2 males (13, 24 years) were enrolled. Cystine capacity respectively went from baseline of −312, −82, −353, and −628 mg/L to 97, 111, 75, and −3 mg/L on high dose (Figure 1). Twenty-four-hour volume went from 1.96, 3.0, 2.1, and 0.91 L to 11.74, 6.5, 9.9, and 2.8 L on high dose (Figure 2). There were no abnormalities in serum electrolytes or liver enzymes. Subjects did experience extreme thirst (9/10 on visual scale), but none discontinued treatment or reduced dose. Conclusion Dilutional therapy with tolvaptan increased both cystine capacity and urinary volumes. This treatment approach has the potential to reduce recurrence of stones in this population. Further investigation should study longer term effects and safety, and determine optimal dosing to improve tolerability.

Resectional and artificial cordal repair techniques are effective strategies for degenerative mitral valve (MV) repair. However, resectional repair requires a tailored approach using various techniques, whereas cordal repair offers a simpler, easily reproducible repair. The approach described in this study approach has evolved from resectional to cordal over time, and outcomes are compared between the eras.Clinical and echocardiographic outcomes of all patients undergoing MV repair for degenerative mitral regurgitation (MR) from January 2004 to September 2017 were reviewed. Patients were stratified by era: from January 2004 to June 2011 (era 1; n = 405), resectional techniques were used in 62% and artificial cordal techniques were used in 38%. From July 2011 to September 2017 (era 2; n = 438), artificial cordal repair was used in 98% of patients. The primary outcome was repair failure, defined as greater than moderate MR or MV reoperation.Of 847 patients with degenerative MR, successful repair was achieved in 843 patients (99.5% repair rate). Leaflet prolapse was posterior in 66%, anterior in 8%, and bileaflet in 26%. Cardiopulmonary bypass time and cross-clamp times were shorter in era 2 (CPB: 109 [IQR, 92-128] minutes vs 97 [IQR, 76-121] minutes; P.001; cross-clamp: 88 [IQR, 73-106] minutes vs. 79 [IQR, 61-99] minutes; P.001). Predismissal echocardiography demonstrated no MR or trace MR in 95%, mild MR in 4.7%, and moderate MR in 0.3% of patients. Operative mortality was similar in the eras (0.5% vs 0.5%; P.999). The rates of 5-year freedom from repair failure (95.1% vs 95.5%; P = .707), stroke (96.8% vs 95.3%; P = .538), and endocarditis (99.3% vs 99.7%; P = .604) were similar between the eras.Artificial cordal repair for all patients with degenerative MR simplifies MV repair and yields equivalent, excellent outcomes compared with a tailored resectional approach.

Introduction: Extracorporeal membrane oxygenation circuit performance can be compromised by oxygenator thrombosis. Stagnant blood flow in the oxygenator can increase the risk of thrombus formation. To minimize thrombogenic potential, computational fluid dynamics is frequently applied for identification of stagnant flow conditions. We investigate the use of computed tomography angiography to identify flow patterns associated with thrombus formation. Methods: A computed tomography angiography was performed on a Quadrox D oxygenator, and video densitometric parameters associated with flow stagnation were measured from the acquired videos. Computational fluid dynamics analysis of the same oxygenator was performed to establish computational fluid dynamics–based flow characteristics. Forty-one Quadrox D oxygenators were sectioned following completion of clinical use. Section images were analyzed with software to determine oxygenator clot burden. Linear regression was used to correlate clot burden to computed tomography angiography and computational fluid dynamics–based flow characteristics. Results: Clot burden from the explanted oxygenators demonstrated a well-defined pattern, with the largest clot burden at the corner opposite the blood inlet and outlet. The regression model predicted clot burden by region of interest as a function of time to first opacification on computed tomography angiography (R2 = 0.55). The explanted oxygenator clot burden map agreed well with the computed tomography angiography predicted clot burden map. The computational fluid dynamics parameter of residence time, when summed in the Z-direction, was partially predictive of clot burden (R2 = 0.35). Conclusion: In the studied oxygenator, clot burden follows a pattern consistent with clinical observations. Computed tomography angiography–based flow analysis provides a useful adjunct to computational fluid dynamics–based flow analysis in understanding oxygenator thrombus formation.

Study design Observational. Objectives To report on the rate of major complications following spinal fusion and instrumentation to treat spinal deformity in patients with cerebral palsy (CP). Summary of background data Understanding the risk of major complications following the surgical treatment of spine deformities in patients with CP is critical. Methods A prospectively collected, multicenter database of patients with CP who had surgical correction of their spinal deformity (scoliosis or kyphosis) was reviewed for all major complications. Patients with ≥ 2 year follow-up or who died ≤ 2 years of surgery were included. A complication was defined as major if it resulted in reoperation, re-admission to the hospital, prolongation of the hospital stay, was considered life-threatening, or resulted in residual disability. Overall complication and revision rates were calculated for the perioperative (Peri-op; occurring ≤ 90 days postoperative) and delayed postoperative (Delayed; > 90 days) time periods. Results Two hundred and fifty-seven patients met inclusion. Seventy-eight (30%) patients had a major complication, 18 (7%) had > 1. There were 92 (36%) major complications; 64 (24.9%) occurred Peri-op. The most common Peri-op complications were wound (n = 16, 6.2%) and pulmonary issues (n = 28, 10.9%), specifically deep infections (n = 12, 4.7%) and prolonged ventilator support (n = 21, 8.2%). Delayed complications (n = 28, 10.9%) were primarily deep infections (n = 8, 3.1%) and instrumentation-related (n = 6, 2.3%). There were 42 additional surgeries for an overall unplanned return to the operating room rate of 16% (Peri-op: 8.6%, Delayed: 7.8%). Thirty-six (14.0%) reoperations were spine related surgeries (wound or instrumentation-related). Eleven (4.3%) patients died between 3 months to 5.6 years postoperatively; 4 occurred ≤ 1 year of surgery. Two deaths were directly related to the spinal deformity surgery. Conclusion Spinal deformity surgery in CP patients with greater than 2 years of follow-up have a postoperative major complication rate of 36% with a spine-related reoperation rate of 14.0%. Level of evidence Therapeutic-IV.

Background Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has emerged as a promising initial support strategy for acute massive pulmonary embolism. However, it remains unclear which patients will ultimately require surgical pulmonary embolectomy (SPE) vs anticoagulation alone. Methods All consecutive patients (2015-2018) with confirmed massive PE, placed on VA-ECMO utilizing a protocolized approach, were reviewed. Per protocol, patients were supported for 3 to 5 days before reevaluation of right ventricular (RV) function via echocardiography. If RV function recovered, VA-ECMO was discontinued with no further intervention (no-SPE group). In patients with persistent RV dysfunction, SPE was performed. Results Forty-five patients were identified, and 41 patients were treated per protocol. Seventy-three percent responded to anticoagulation alone, and 27% required SPE. Factors associated with SPE rather than decannulation with anticoagulation alone included prolonged shortness of breath, elevated N-terminal prohormone of brain natriuretic peptide, enlarged pulmonary artery diameter, and history of venous thromboembolism. A predictive algorithm was developed with a negative predictive value of 97% and a specificity of 97% for a low-risk score, and a positive predictive value of 100% and sensitivity of 67% for a high-risk score. Overall, 90-day survival was 97% in the no-SPE group and 100% in the SPE group. Conclusions In this cohort, greater than 70% of patients who presented with massive PE and supported with VA-ECMO ultimately recovered with anticoagulation alone. Specific risk factors, likely related to thrombus chronicity, may be associated with lack of RV recovery, and can be utilized for consideration of early surgical intervention to minimize VA-ECMO duration.

Background. Individuals with cystic fibrosis (CF) have persistent lung infections, necessitating the frequent use of antibiotics for pulmonary exacerbations. Some respiratory pathogens have intrinsic resistance to the currently available antibiotics, and any pathogen may acquire resistance over time, posing a challenge to CF care. Gaseous nitric oxide has been shown to have antimicrobial activity against a wide variety of microorganisms, including common CF pathogens, and offers a potential inhaled antimicrobial therapy. Case Presentation. Here, we present the case of a 16-year-old female with CF who experienced a precipitous decline in lung function over the prior year in conjunction with worsening antibiotic resistance of her primary pathogen, Burkholderia multivorans. She received 46 intermittent inhalations of 160 parts-per-million nitric oxide over a 28-day period. The gas was administered via a mechanical ventilator fitted with nitrogen dioxide scavenging chambers. Conclusions. High-dose inhaled nitric oxide was safe, well tolerated, and showed clinical benefit in an adolescent with cystic fibrosis and pulmonary colonization with Burkholderia multivorans.

Background Despite improved survival and morbidity after durable left ventricular assist device (dLVAD), outcomes for cardiogenic shock patients are suboptimal. Temporary mechanical circulatory support (tMCS) can permit optimization before dLVAD. Excellent outcomes have been observed using minimally-invasive dLVAD implantation. However, some feel tMCS contraindicates this approach. To evaluate whether left thoracotomy/hemisternotomy (LTHS) dLVAD placement is safe in this setting, we compared patients who did and did not require tMCS. Methods Outcomes for patients receiving dLVADs via LTHS were compared among those bridged with extracorporeal membrane oxygenation (ECMO), intra-aortic balloon pump (IABP), or no tMCS. We evaluated demographics, comorbidities, laboratory and hemodynamic data, and intraoperative and postoperative outcomes. Results Eighty-three patients underwent LTHS dLVAD placement. Fifty did not require tMCS, while 22 (26%) required IABP, and 11 (13%) ECMO. Non-tMCS patients were primarily Intermacs 3 (56%), while IABP recipients were mainly Intermacs 2 (45%). All patients with ECMO were Intermacs 1. Patients with tMCS had worse end-organ function. Operative outcomes were similar except more concomitant procedures and red-cell transfusions in patients with ECMO. Intensive care unit and hospital length of stay and inotrope duration were also similar. There were no differences in bleeding, stroke, and infection rates. Three- and 12-month survival were: no tMCS: 94%, 86%; IABP: 100%, 88%; and ECMO: 81%, 81% (P = .45). Conclusions Patients with cardiogenic shock can safely undergo LTHS dLVAD implantation after stabilization with ECMO or IABP. Outcomes and complications in these patients were comparable to a less severely ill cohort without tMCS.

Retrospective study. To analyze the relationships between three-dimensional (3D) measurements of spinal deformity and Scoliosis Research Society-22 (SRS-22) scores in preoperative patients with major thoracic adolescent idiopathic scoliosis (AIS). Previous studies reported 2D measurements were not or only weakly correlated with preoperative SRS-22 scores. However, 2D measures do not always accurately represent the 3D deformity. A multicenter prospective registry of surgically treated AIS patients was reviewed for patients with right major thoracic AIS (Lenke type 1–4) who underwent biplanar radiography and completed the SRS-22 questionnaire preoperatively. For the 3D measurements, two reference frames were utilized: global (gravity/patient-based) and local (vertebra/disc-based). To obtain regional measurements, the individual segments in the appropriate reference plane were summed between the levels of interest. Patients were divided into two groups for each SRS-22 domain according to their scores: low (

Retrospective. Utilize three-dimensional (3D) measurements to assess the relationship between thoracic scoliosis severity and thoracic kyphosis in a large, multicenter cohort, and determine impact of 3D measurements on adolescent idiopathic scoliosis (AIS) curve classification. Research has demonstrated differences in two-dimensional (2D) and 3D assessment of the sagittal plane deformity in AIS. A prior smaller, single-institution study demonstrated an association between scoliosis severity and loss of 3D thoracic kyphosis. Data included retrospective compilation of prospectively enrolled bracing candidates and prospectively enrolled surgical candidates with thoracic AIS. Analysis included two groups based on thoracic curve magnitude: moderate (20–45°) and severe (> 45°). Imaging was performed using 2D radiographs. 3D thoracic kyphosis was calculated using a 2D to 3D conversion formula. Kyphosis was categorized according to the Lenke classification sagittal plane modifier. Analysis included 3032 patients. 2D kyphosis was significantly less in the moderate group (21 ± 12 vs 23 ± 14, p = 0.028). However, estimated 3D kyphosis was significantly greater in the moderate group (13 ± 10 vs 5 ± 12, p

Background and study aims Endoscopic resection is recommended as initial treatment for early-stage gastric and duodenal neuroendocrine tumors (G-NETs and D-NETs). However, it can cause serious adverse events. We aimed to evaluate the efficacy and safety of the band and slough (BAS) technique as a novel and less aggressive endoscopic therapy for management of such tumors.Four patients, three diagnosed with The BAS technique may prove to be a safe and effective endoscopic therapy for diminutive, non-metastatic type 1 G-NETs and D-NETs. Studies of larger scale and longer follow-up periods are needed to corroborate these findings.

STUDY DESIGN Retrospective. OBJECTIVE To evaluate the effect of preoperative rod shape on 3D spinal deformity correction. SUMMARY OF BACKGROUND DATA Differential rod contouring is a surgeon-dependent process based on an estimate of 3D deformity correction sought and the flexibility of the spine. An objective measure to this otherwise subjective scoliosis correction technique is lacking. METHODS A series of adolescent idiopathic scoliosis (AIS) patients with right, thoracic major curves, preoperative rod contour tracings, and EOS imaging was evaluated. All patients underwent posterior spinal fusion with 5.5 mm steel rods contoured prior to insertion. 3D reconstructions were generated pre- and postoperatively using sterEOS software (EOS Imaging) and imported into MATLAB (Mathworks) for analysis. A new measurement of the maximum perpendicular distance from the preinsertion concave rod contour to the preoperative 3D sagittal spinal reconstruction was defined as rod to 3D spine distance (RSD). Linear regressions were used to identify relationships between pre and postoperative parameters, including RSD and 3D thoracic kyphosis. RESULTS Ninety-nine patients were included. Average preoperative concave rod angle decreased from (48 ± 10°) preoperatively to 26 ± 6° postoperatively (P

Objective Chronological age is a risk factor in chronic pain; however, aging research supports the premise that physical and psychological health may better predict perceived age. Given the lack of evidence on perceived age in the context of chronic pain, the current study presents novel findings about the relationship between perceived age, chronic pain impact, and psychological function in adults with and without knee osteoarthritis. Methods This secondary analysis was part of an ongoing multisite observational cohort study to understand the progression of knee pain and disability. Community-dwelling adults (N=227) ages 45+ completed measures of trait resilience, trait positive and negative affect, pain catastrophizing, subjective perceptions of age, and the Graded Chronic Pain Scale. Results On average, participants reported feeling 10 years younger than their chronological age; however, this effect was attenuated in individuals reporting high-impact pain. Lower perceived age was associated with lower pain impact (low pain/low disability), while higher perceived age correlated with higher pain impact (high pain/high disability) and more adverse psychological effects. Using hierarchical linear regression, high-impact pain and positive affect emerged as statistically significant predictors of perceived age, whereas no differences were observed among trait resilience, negative affect, or pain catastrophizing. Discussion These findings highlight the importance of a biopsychosocial approach in understanding the intersection between psychological and physical factors associated with chronic pain. Addressing negative self-perceptions of aging, while simultaneously augmenting positive affect, through psychological therapies may mitigate pain and disability.

Patients supported with venovenous extracorporeal membrane oxygenation are at risk for intra-abdominal hypertension and abdominal compartment syndrome. Flow through the return cannula may be compromised in these patients, resulting in inadequate support and end-organ malperfusion. Early decompressive laparotomy can mitigate these complications and potentially improve outcomes. Here we review a series of nine patients undergoing early decompressive laparotomy for abdominal compartment syndrome at a single institution and propose an algorithmic approach to the management of these patients.

Purpose Research indicates pain-related disparities in the impact of knee osteoarthritis (OA) across both sex and ethnicity/race. While several factors likely contribute to these disparities, experiences of discrimination are associated with poor OA-related pain, disability, and functional performance. However, the mechanisms that mediate experiences of discrimination and OA-related outcomes are unclear. The current cross-sectional study examined the associations between everyday experiences of discrimination and clinical pain, disability and functional performance among non-Hispanic Black (NHB) and non-Hispanic White (NHW) persons with or at risk of knee OA and assessed the serial mediated model of perceived stress and pain catastrophizing on these relationships in women only. Patients and Methods Participants were 188 community-dwelling adults who presented with unilateral or bilateral knee pain and screened positive for clinical knee pain. Participants completed several measures including experiences of discrimination, Perceived Stress Scale, Coping Strategies Questionnaire-Revised (CSQ-R): Pain Catastrophizing subscale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Graded Chronic Pain Scale (GCPS), and Short Physical Performance Battery (SPPB). Results As compared to NHW participants, NHB individuals reported experiencing significantly higher levels of discrimination (F(1, 175)=26.660, p

Background Many individuals with cystic fibrosis (CF) die from respiratory failure without referral for lung transplant. Physician practices that may expedite, delay, or preclude referral, are poorly understood. Methods Two parallel, web-based surveys focusing on lung transplant referral triggers and barriers, as well as pre-referral evaluation, were emailed to pulmonologists practicing in the New England region. One questionnaire was sent to CF providers (n = 61), and the second to general pulmonary providers practicing at the same institutions (n = 61). Results There were 43 (70%) responses to the CF provider survey, and 25 (41%) responses to the general pulmonary (‘non-CF’) provider survey. Primary reasons for CF providers to refer their patients included: rapidly declining lung function (91%) and a forced expiratory volume in 1 s (FEV1) below 30% predicted (74%). The greatest barriers to referral for both CF and non-CF providers included active tobacco use (65 and 96%, respectively, would not refer), and active alcohol or other substance use or dependence (63 and 80%). Furthermore, up to 42% of CF providers would potentially delay their referral if triple-combination therapy or other promising new, disease-specific therapy were anticipated. In general, non-CF providers perform a more robust pre-referral medical work-up, while CF providers complete a psychosocial evaluation in higher numbers. Across both groups, communication with lung transplant programs was reported to be inadequate. Conclusions Physician-level barriers to timely lung transplant referral exist and need to be addressed. Enhanced communication between lung transplant programs and pulmonary providers may reduce these barriers.

Left ventricular assist devices are routinely used to treat patients with advanced heart failure as a bridge to transplant or a destination therapy. However, non-physiological shear stress generated by left ventricular assist devices damages blood cells. The continued development of novel left ventricular assist devices is essential to improve the left ventricular assist device therapy for heart failure patients. The CH-VAD is a new maglev centrifugal left ventricular assist device. In this study, the CH-VAD pump was numerically analyzed and compared with the HVAD and HeartMate II pumps under two clinically relevant conditions (flow: 4.5 L/min, pressure head: normal ~80 and hypertension ~120 mmHg). The velocity and shear stress fields, washout, and hemolysis index of the three pumps were assessed with computational fluid dynamics analysis. Under the same condition, the CH-VAD hemolysis index was two times lower than the HVAD and HeartMate II pumps; the CH-VAD had the least percentage volume with shear stress larger than 100 Pa (i.e. normal condition: 0.4% vs HVAD 1.0%, and HeartMate II 2.9%). Under the normal condition, more than 98% was washed out of the three pumps within 0.4 s. The washout times were slightly shorter under the hypertension condition for the three pumps. No regions inside the CH-VAD or HVAD had extremely long residential time, while areas near the straightener of the HeartMate II pump had long residential time (>4 s) indicating elevated risks of thrombosis. The computational fluid dynamics results suggested that the CH-VAD pump has a better hemolytic biocompatibility than the HVAD and HeartMate II pumps under the normal and hypertension conditions.

Background Chronic subdural haematoma (CSDH) is a pathology that is frequently encountered by neurosurgeons. Nevertheless, there is a lack of guidelines based on solid evidence. There has been a recent and considerable increase in the interest on management and outcomes for CSDH. Therefore, we systematically reviewed all currently running randomised controlled trials (RCTs) in chronic subdural haematoma to understand the areas under investigation and plan future collaborative trials. Methods Clinical trials databases (Cochrane Controlled Register of Trials, WHO ICTRP and clinical trials.gov) were searched for trials relevant to chronic subdural haematoma. It was then established which trials were currently running and fulfilled robust research methodology for a RCT. Results There are 26 currently running RCTs in CSDH, with the most common topics covering application of steroids (7), surgical techniques (5) and tranexamic acid (5). Further to this, there are trials running on other pharmacological agents (4), middle meningeal artery (MMA) embolisation (2) and peri-operative management (3). Conclusions Pharmacological agents are a particular focus of CSDH management currently, and a wealth of studies on steroids will hopefully lead to more harmonised, evidence-based practice regarding this in the near future. Surgical techniques and new procedures such as MMA embolisation are also important focuses for improving patient outcomes. There is an on-going need for future RCTs and evidence-based guidelines in CSDH, particularly including low- and middle-income countries, and it is hoped that the establishment of the iCORIC (International COllaborative Research Initiative on Chronic Subdural Haematoma) will help address this.

The AP-2γ transcription factor, encoded by the TFAP2C gene, regulates the expression of estrogen receptor-alpha (ERα) and other genes associated with hormone response in luminal breast cancer. Little is known about the role of AP-2γ in other breast cancer subtypes. A subset of HER2+ breast cancers with amplification of the TFAP2C gene locus becomes addicted to AP-2γ. Herein, we sought to define AP-2γ gene targets in HER2+ breast cancer and identify genes accounting for physiologic effects of growth and invasiveness regulated by AP-2γ. Comparing HER2+ cell lines that demonstrated differential response to growth and invasiveness with knockdown of TFAP2C, we identified a set of 68 differentially expressed target genes. CDH5 and CDKN1A were among the genes differentially regulated by AP-2γ and that contributed to growth and invasiveness. Pathway analysis implicated the MAPK13/p38δ and retinoic acid regulatory nodes, which were confirmed to display divergent responses in different HER2+ cancer lines. To confirm the clinical relevance of the genes identified, the AP-2γ gene signature was found to be highly predictive of outcome in patients with HER2+ breast cancer. We conclude that AP-2γ regulates a set of genes in HER2+ breast cancer that drive cancer growth and invasiveness. The AP-2γ gene signature predicts outcome of patients with HER2+ breast cancer and pathway analysis predicts that subsets of patients will respond to drugs that target the MAPK or retinoic acid pathways. Implications: A set of genes regulated by AP-2γ in HER2+ breast cancer that drive proliferation and invasion were identified and provided a gene signature that is predictive of outcome in HER2+ breast cancer.

Background: Structural valve deterioration (SVD) is the Achilles heel of bioprosthetic valves used for aortic valve replacement (AVR). SVD has been traditionally defined based upon the requirement ...

Familial adenomatous polyposis (FAP) patients are at risk for numerous malignancies. Multiple surgeries exist to mitigate the risk of colorectal cancer. Surgeons must weigh future quality of life versus the risk of dysplasia. As FAP patient longevity increases, there remains a risk of other malignancies. This study examines surgical interventions, development of cancers, and causes of mortality in a FAP registry. Patients with FAP or attenuated FAP (aFAP) were identified by linking the Hereditary Gastrointestinal Cancer Registry with University of Utah’s medical records. Patients without sufficient information were excluded. Patient demographics, surgical histories, cancer diagnoses, and causes of death were extracted. Logrank and Fisher’s exact tests were employed to detect significant differences between groups. After exclusion criteria, 140 patients were analyzed. Sixty patients (42.9%) underwent total proctocolectomy with ileal pouch-anal anastomosis (IPAA) followed by 50 (35.7%) having total colectomy with ileorectal anastomosis (IRA). IPAA patients were more likely female (p = 0.01) and have FAP (p

Background Chronic subdural hematomas (cSDH) are one of the most common conditions requiring neurosurgical treatment. The reported recurrence after surgery is 3–21.5% with closed system drainage. In clinical practice, irrigation fluids at body temperature (37 °C) and at room temperature (22 °C) are routinely used in the evacuation of cSDH. Our hypothesis was that irrigation at body temperature might have more beneficial effects on coagulation and solubility of the chronic subdural hematoma than irrigation at room temperature. The aim of this study was to compare the effects of different intraoperative irrigation fluid temperatures on recurrence rates. Methods This was a retrospective study where we included all consecutive patients from a defined geographical area of western Sweden between September 2013 and November 2014. In the course of 6 months, we performed intraoperative irrigation at body temperature (37 °C, BT-group) during burr hole evacuation of chronic subdural hematoma. This was then compared with the previous 6-month period, when irrigation fluid at room temperature (22 °C, RT-group) was used. The primary endpoint was same-sided recurrence in need of reoperation within 6 months. Results Recurrence occurred in 11 of 84 (13.1%) patients in the RT-group compared with 4 of 88 (4.5%) in the BT-group (p = 0.013). There were no significant between-group differences regarding age, sex, duration of surgery, frequency of bilateral hematomas, hematoma density, and use of anticoagulant/antithrombotic therapy. Conclusion Our study demonstrates that intraoperative irrigation fluid at body temperature is associated with lower recurrence rates compared with irrigation fluid at room temperature. To investigate this further, a prospective randomized controlled trial has been initiated (clinicaltrials.gov, NCT0275235). Trial registration ClinicalTrials.gov Identifier: NCT0275235