Real world study of sacituzumab govitecan in metastatic triple-negative breast cancer in the United Kingdom.

BACKGROUND: Treatment options for pre-treated patients with metastatic triple-negative breast cancer (mTNBC) remain limited. This is the first study to assess the real-world safety and efficacy of sacituzumab govitecan (SG) in the UK. METHODS: Data was retrospectively collected from 16 tertiary UK cancer centres. Pts had a diagnosis of mTNBC, received at least two prior lines of treatment (with at least one being in the metastatic setting) and received at least one dose of SG. RESULTS: 132 pts were included. Median age was 56 years (28-91). All patients were ECOG performance status (PS) 0-3 (PS0; 39, PS1; 76, PS2; 16, PS3;1). 75% (99/132) of pts had visceral metastases including 18% (24/132) of pts with CNS disease. Median PFS (mPFS) was 5.2 months (95% CI 4.5-6.6) with a median OS (mOS) of 8.7 months (95% CI 6.8-NA). The most common adverse events (AEs) were fatigue (all grade; 82%, G3/4; 14%), neutropenia (all grade; 55%, G3/4; 29%), diarrhoea (all grade; 58%, G3/4, 15%), and nausea (all grade; 38%, G3/4; 3%). SG dose reduction was required in 54% of pts. CONCLUSION: This study supports significant anti-tumour activity in heavily pre-treated pts with mTNBC. Toxicity data aligns with clinical trial experience.

A Prospective Study of Sentinel Node Biopsy Omission in Women Age ≥ 65 Years with ER+ Breast Cancer.

BACKGROUND: National guidelines recommend omitting SNB in older patients with favorable invasive breast cancer. However, there is a lack of prospective data specifically addressing this issue. This study evaluates recurrence and survival in estrogen receptor-positive/Her2- (ER+) breast cancer patients, aged ≥ 65 years who have breast-conserving surgery (BCS) without SNB. METHODS: This is a prospective, observational study at a single institution where 125 patients aged ≥ 65 years with clinical T1-2N0 ER+ invasive breast cancer undergoing BCS were enrolled. Patients were treated with BCS without SNB. Primary outcome measure was axillary recurrence. Secondary outcome measures include recurrence-free survival (RFS), disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS). RESULTS: From January 2016 to July 2022, 125 patients were enrolled with median follow-up of 36.7 months [95% confidence interval (CI) 35.0-38.0]. Median age was 77.0 years (range 65-93). Median tumor size was 1 cm (range 0.1-5.0). Most tumors were ductal (95/124, 77.0%), intermediate grade (60/116, 51.7%), and PR-positive (117/123, 91.7%). Radiation therapy was performed in 37 of 125 (29.6%). Only 60 of 125 (48.0%) who were recommended hormonal therapy were compliant at 2 years. Chemotherapy was administered to six of 125 (4.8%) patients. There were two of 125 (1.6%) axillary recurrences. Estimated 3-years rates of regional RFS, DFS, and OS were 98.2%, 91.2%, and 94.8%, respectively. Univariate Cox regression identified hormonal therapy noncompliance to be significantly associated with recurrence (p = 0.02). CONCLUSIONS: Axillary recurrence rates were extremely low in this cohort. These results provide prospective data to support omission of SNB in this patient population TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02564848.

Implementation of Exercise Management Services Among Sports Medicine Physicians in the United States.

OBJECTIVE: Assessment of physical activity and exercise prescription has been widely supported by many organizations, yet provision of such services remains limited in the United States. We sought to uncover why such services have not been widely adopted. DESIGN: The American Medical Society for Sports Medicine organized a task force to canvas physicians and survey the American Medical Society for Sports Medicine membership. SETTING: Peer-to-peer and telecommunication discussions and web-based questionnaires. PARTICIPANTS: Sports medicine physicians in the United States. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Percentage of sports medicine physicians who provide exercise management services and mechanisms of billing for exercise management, identify barriers to such services, and identify industry collaborations for promoting physical activity through physicians. RESULTS: Three of 4 sports medicine physicians spend at least 1 min encouraging exercise with patients, using Evaluation and Management codes to bill or receive credit. Exercise counseling is often bundled within other patient care. Few health plans leverage the patient's relationship with a primary care physician to promote exercise. Most employed sports medicine physicians do not receive incentives to incorporate exercise counseling into practice, and only 1 in 6 have decision-making authority to hire an exercise professional. Major obstacles are the lack of a business model and knowledge about exercise prescription. CONCLUSION: The existing E&M codes adequately characterize the work, but physicians desire greater payment or credit for providing exercise management services. Physicians desire to do more exercise prescription, but health system bureaucracy, inadequate support, and economic disincentives are barriers to the provision of exercise management services.

Different-sized extracellular vesicles derived from stored red blood cells package diverse cargoes and cause distinct cellular effects.

BACKGROUND: The formation of extracellular vesicles (EVs) occurs during cold storage of RBCs. Transfusion of EVs may contribute to adverse responses in recipients receiving RBCs. However, EVs are poorly characterized with limited data on whether distinct vesicles are formed, their composition, and potential biological effects. STUDY DESIGN AND METHODS: Stored RBC-derived EVs were purified using protocols that separate larger microvesicle-like EVs (LEVs) from smaller exosome-like vesicles (SEVs). Vesicles were analyzed by electron microscopy, content of hemoglobin, heme, and proteins (by mass spectrometry), and the potential to mediate lipid peroxidation and endothelial cell permeability in vitro. RESULTS: SEVs were characterized by having an electron-dense double membrane whereas LEVs had more uniform electron density across the particles. No differences in hemoglobin nor heme levels per particle were observed, however, due to smaller volumes, SEVs had higher concentrations of oxyHb and heme. Both particles contained antioxidant proteins peroxiredoxin-2 and copper/zinc superoxide dismutase, these were present in higher molecular weight fractions in SEVs suggesting either oxidized proteins are preferentially packaged into smaller vesicles and/or that the environment associated with SEVs is more pro-oxidative. Furthermore, total glutathione (GSH + GSSG) levels were lower in SEVs. Both EVs mediated oxidation of liposomes that were prevented by hemopexin, identifying heme as the pro-oxidant effector. Addition of SEVs, but not LEVs, induced endothelial permeability in a process also prevented by hemopexin. CONCLUSION: These data show that distinct EVs are formed during cold storage of RBCs with smaller particles being more likely to mediate pro-oxidant and inflammatory effects associated with heme.

Adrenocortical Carcinoma: The Value of Lymphadenectomy.

BACKGROUND: Adrenocortical carcinoma (ACC) staging does not account for the number of positive nodes. The prognostic value of quantitative metastatic nodal burden is unknown. METHODS: The National Cancer Database was retrospectively queried from 2004-2016 to identify patients with Stage I-III ACC undergoing adrenalectomy. Patients who underwent lymphadenectomy (LAD) were further studied. Demographics, TNM staging, tumor characteristics, and surgical approach were analyzed. RESULTS: 386 LADs were identified. The median number of nodes examined was 2 (IQR 2-6), with no difference by surgical approach '[laparoscopic, 3 (1-3); robotic, 1.5 (1-4.5); open, 2 (1-7), p = 0.493]. In LADs with cN0 disease, positive nodes were seen in 17.5% of patients; an average of 6 (1-12) nodes were examined in patients who upstaged to pN1 disease compared with an average of 2 (1-6) nodes in those who remained pN0. Median survival was incrementally worse for patients with more positive nodes (62.8 vs. 21.9 vs. 13.7 vs. 11.3 vs. 10.7 months for 0, 1, 2, 3, and ≥ 4 positive nodes, respectively, p < 0.01). On multivariate analysis, significant prognostic factors for poor survival included older age, ≥ 2 comorbidities, pT3, and pT4. The strongest prognostic factor for poor survival was the number of positive nodes (1 node, hazards ratio [HR] 2.3, 95% confidence interval [CI] 1.5-3.6; 2 nodes, HR 1.3, 95% CI 0.6-3.0; 3 nodes, HR 3.0, 95% CI 1.1-8.0; ≥ 4 nodes, HR 4.0, 95% CI 2.5-6.2). Lymphadenectomy was associated with improved survival (HR 0.82, 95% CI 0.67-0.99). CONCLUSIONS: Higher quantitative metastatic nodal burden is a robust prognostic factor for worse survival in ACC.

Percutaneous Cholecystostomy Tube for Acute Cholecystitis: Quantifying Outcomes and Prognosis.

BACKGROUND: Percutaneous cholecystostomy tubes (PCT) are utilized in the management of acute cholecystitis in patients deemed unsuitable for surgery. However, the drive for these decisions and the outcomes remain understudied. We sought to characterize the practices and utilization of PCT and evaluate associated outcomes at an urban medical center. METHODS: Patients undergoing PCT placement over a 12-y study period ending May 2019 were reviewed. Demographics, clinical presentation, labs, imaging studies, and outcomes were abstracted. The primary and secondary outcomes were 30-d mortality and interval cholecystectomy, respectively. RESULTS: Two hundred and four patients met inclusion criteria: 59.3% were male with a median age of 67.5 y and a National Surgical Quality Improvement Program (NSQIP) risk of serious complication of 8.0%. Overall, 57.8% of patients were located in an intensive care unit setting. The majority (80.9%) had an ultrasound and 48.5% had a hepatobiliary iminodiacetic acid scan. The overall 30-d mortality was 31.9%: 41.5% for intensive care unit and 18.6% for ward patients (P < 0.01). Of patients surviving beyond 30 d (n = 139), the PCT was removed from 106 (76.3%), and a cholecystectomy was performed in 55 (39.6%) at a median interval of 58.0 d. A forward logistic regression identified total bilirubin (Adjusted Odds Ratio: 1.12, adjusted P < 0.01) and NSQIP risk of serious complication (Adjusted Odds Ratio: 1.16, adjusted P < 0.01) as the only predictors for 30-d mortality. CONCLUSIONS: Patients selected for PCT placement have a high mortality risk. Despite subsequent removal of the PCT, the majority of surviving patients did not undergo an interval cholecystectomy. Total bilirubin and NSQIP risk of serious complication are useful adjuncts in predicting 30-d mortality in these patients.

Operative approach and case volume are associated with negative resection margins for adrenocortical carcinoma.

BACKGROUND: Surgical resection with negative margins is the treatment of choice for adrenocortical carcinoma (ACC). This study was undertaken to determine factors associated with negative resection margins. METHODS: National Cancer Database was queried from 2010 to 2016 to identify patients with AJCC/ENSAT Stage I-III ACC who underwent adrenalectomy. Patient, tumor, facility, and operative characteristics were compared by margin status (positive-PM or negative-NM) and operative approach (open-OA, laparoscopic-LA, or robotic-RA). Multivariable logistic regression was used to identify factors associated with PM. RESULTS: Eight hundred and eighty-one patients were identified, of which 18.4% had PM and 81.6% had NM. Patients with advanced pathologic T stage and pathologic N1 stage were more likely to have PM (vs. NM) (T3, 49.7% vs. 24.8%, p < 0.01; T4, 26.2% vs. 10.0%, p < 0.01; N1, 6.7% vs. 3.5%, p < 0.01). Patients undergoing OA (vs. LA and RA) were more likely to have advanced clinical T stage (T4, 16.6% vs. 5.7% vs. 7.8%, p < 0.01) and larger tumors (> 6 cm, 84.6% vs. 64.1% vs. 62.3%, p < 0.01). High-volume centers (≥ 5 cases) were more likely to utilize OA. Patients undergoing LA (vs. RA) were more likely to require conversion to open (20.3% vs. 7.8%, p = 0.011). On multivariable analysis, factors associated with higher odds of PM included T3 disease (OR 7.02, 95% CI 2.66-18.55), T4 disease (OR 10.22, 95% CI 3.66-28.53), and LA (OR 1.99, 95% CI 1.28-3.09). High-volume centers were associated with lower odds of PM (OR 0.67, 95% CI 0.45-0.98). There was no significant difference in margin status between OA and RA (OR 1.44, 95% CI 0.71-2.90). CONCLUSION: Centers with higher ACC case volumes have lower odds of PM and utilize OA more often. LA is associated with higher odds of PM, whereas RA is not. These factors should be considered when planning the operative approach for ACC.

Outcomes Following Percutaneous Cholecystostomy Tube Placement for Acalculous Versus Calculous Cholecystitis.

BACKGROUND: Acute acalculous cholecystitis (AAC) is often diagnosed in critically ill patients. Percutaneous cholecystostomy tube (PCT) placement facilitates less invasive gallbladder decompression in patients who are poor surgical candidates. Specific guidelines for optimal management of AAC patients following PCT placement remain to be defined. We hypothesize that AAC patients are at lower risk of recurrent cholecystitis than acute calculous cholecystitis (ACC) patients and do not require cholecystectomy after PCT placement. METHODS: A retrospective review of patients who underwent PCT placement for AAC or ACC between 6/1/2007 and 5/31/2019 was performed. Primary outcome was recurrent cholecystitis and interval cholecystectomy for patients surviving 30 days after PCT placement. Secondary outcome was 30 day mortality. A cox regression model calculated the adjusted hazard ratio (AHR) for the outcomes. RESULTS: Eighty-four AAC and 85 ACC patients underwent PCT placement. Compared to ACC patients, more AAC patients were male (72.6 vs. 48.2%; p < 0.01), younger (median age 62 vs. 73 years; p < 0.01), and required intensive care (69.0 vs. 52.9%; p = 0.04), with lower median Charlson Comorbidity Index (4.0 vs. 6.0; p < 0.01). 30 day mortality was higher among AAC patients than ACC patients (45.2 vs. 21.2%; p < 0.01). 2/24 (8.3%) AAC patients and 5/31 (16.1%) ACC patients developed recurrent cholecystitis at a median 208.0 days (IQR:64.0-417.0) after PCT placement and 115.0 days (IQR:7.0-403.0) following PCT removal. Cox regression analysis demonstrated that AAC patients had lower likelihood of interval cholecystectomy compared to ACC patients (AHR 2.35; 95% CI:1.11,4.96). CONCLUSION: Recurrent cholecystitis is rare in patients surviving 30 days following PCT placement. When compared with ACC patients, fewer AAC patients require cholecystectomy.

Factors Associated with Non-Operative Management of Resectable Adrenocortical Carcinoma.

INTRODUCTION: Surgery is the initial treatment of choice for patients with resectable adrenocortical carcinoma (ACC). We sought to determine factors associated with non-operative management of resectable ACC. METHODS: 2004-2016 National Cancer Database (NCDB) was queried to identify patients with AJCC/ENSAT Stage I-III ACC. Patients who underwent surgery (S) were compared to those who did not undergo surgery (NS). Multivariate logistic regression was used to identify factors associated with NS. Kaplan-Meier estimates used to assess survival. RESULTS: Two thousand-seventy patients with Stage I-III ACC were identified, of which 17.5% were NS. 85.9% of NS patients were not offered surgery; 69.9% of NS patients did not receive chemotherapy or radiation therapy. NS were older and less likely to receive care at an Academic center or high volume center (≥5 cases during the study period). NS patients were more likely to have advanced T stage and N1 disease. On multivariate regression, factors associated with lower odds of surgery include older age (OR 1.03, 95% CI 1.02-1.06), T4 disease (OR 3.34, 95% CI 1.05-10.68), and treatment at a community center (OR 2.92, 95% CI 1.58-5.40). Overall median survival was significantly poorer for NS patients (50.4 versus 78.4 months, P < 0.01). CONCLUSION: Patients with locally advanced ACC are less likely to undergo an operation, while those treated at centers with more operative experience or Academic facilities are more likely to undergo an operation. As the surgery-first approach is the current standard of care for resectable ACC, these patients may be best served at high volume Academic facilities.

Comparing clinical outcomes of image-guided percutaneous transperitoneal and transhepatic cholecystostomy for acute cholecystitis.

BACKGROUND: Percutaneous cholecystostomy is performed by interventional radiologists for patients with calculous/acalculous cholecystitis who are poor candidates for cholecystectomy. Two anatomical approaches are widely utilized: transperitoneal and transhepatic. PURPOSE: To compare the clinical outcomes of transperitoneal and transhepatic approaches to cholecystostomy catheter placement. MATERIAL AND METHODS: From December 2007 to August 2015, 165 consecutive patients (97 men, 68 women) underwent either transperitoneal (n = 89) or transhepatic (n = 76) cholecystostomy at a single center. Indications were calculous cholecystitis (n = 21), acalculous cholecystitis (n = 35), hydrops (n = 1), gangrenous cholecystitis (n = 1), and other cholecystitis (n = 107). The most common high-risk co-morbidities were sepsis (n = 53) and cardiac (n = 11). Outcomes were compared using univariate and multivariable analysis. RESULTS: Post-procedure outcomes included tube dislodgement (transperitoneal [n = 6] and transhepatic [n = 3], P = 0.44), bile leak (transperitoneal [n = 5], transhepatic [n = 1], P = 0.14), gallbladder hemorrhage (transperitoneal [n = 2]; transhepatic [n = 3], P = 0.52), duodenal fistula (transperitoneal [n = 0], transhepatic [n = 1], P = 0.27), repeat cholecystostomy (transperitoneal [n = 1], transhepatic [n = 3], P = 0.27), and repeat cholecystitis requiring separate admission (transperitoneal [n = 6], transhepatic [n = 10], P = 0.15). All complications were Common Terminology Criteria for Adverse Events grade <3. Twenty transperitoneal patients underwent post-procedure cholecystectomy: 13 laparoscopic, three open, and four unclear/outside records. The mean time from cholecystostomy to operation was 38 days (range 3-211 days). Twenty-three transhepatic patients underwent cholecystectomy: 14 laparoscopic, eight open, and one unclear/outside records, with the mean time from cholecystostomy being 98 days (range 0-1053 days). One transhepatic and three transperitoneal patients died during admission. CONCLUSION: There were no significant differences in short-term complications after transperitoneal and transhepatic approaches to percutaneous cholecystostomy catheter placement.

SAGES and EAES recommendations for minimally invasive surgery during COVID-19 pandemic.

The unprecedented pandemic of COVID-19 has impacted many lives and affects the whole healthcare systems globally. In addition to the considerable workload challenges, surgeons are faced with a number of uncertainties regarding their own safety, practice, and overall patient care. This guide has been drafted at short notice to advise on specific issues related to surgical service provision and the safety of minimally invasive surgery during the COVID-19 pandemic. Although laparoscopy can theoretically lead to aerosolization of blood borne viruses, there is no evidence available to confirm this is the case with COVID-19. The ultimate decision on the approach should be made after considering the proven benefits of laparoscopic techniques versus the potential theoretical risks of aerosolization. Nevertheless, erring on the side of safety would warrant treating the coronavirus as exhibiting similar aerosolization properties and all members of the OR staff should use personal protective equipment (PPE) in all surgical procedures during the pandemic regardless of known or suspected COVID status. Pneumoperitoneum should be safely evacuated via a filtration system before closure, trocar removal, specimen extraction, or conversion to open. All emergent endoscopic procedures performed during the pandemic should be considered as high risk and PPE must be used by all endoscopy staff.

Randomized Trial of Near-infrared Incisionless Fluorescent Cholangiography.

BACKGROUND: Incisionless near-infrared fluorescent cholangiography (NIFC) is emerging as a promising tool to enhance the visualization of extrahepatic biliary structures during laparoscopic cholecystectomies. METHODS: We conducted a single-blind, randomized, 2-arm trial comparing the efficacy of NIFC (n = 321) versus white light (WL) alone (n = 318) during laparoscopic cholecystectomy. Using the KARL STORZ Image1 S imaging system with OPAL1 technology for NIR/ICG imaging, we evaluated the detection rate for 7 biliary structures-cystic duct (CD), right hepatic duct (RHD), common hepatic duct, common bile duct, cystic common bile duct junction, cystic gallbladder junction (CGJ), and accessory ducts -before and after surgical dissection. Secondary calculations included multivariable analysis for predictors of structure visualization and comparing intergroup biliary duct injury rates. RESULTS: Predissection detection rates were significantly superior in the NIFC group for all 7 biliary structures, ranging from 9.1% versus 2.9% to 66.6% versus 36.6% for the RHD and CD, respectively, with odds ratios ranging from 2.3 (95% CI 1.6-3.2) for the CGJ to 3.6 (1.6-9.3) for the RHD. After dissection, similar intergroup differences were observed for all structures except CD and CGJ, for which no differences were observed. Significant odds ratios ranged from 2.4 (1.7-3.5) for the common hepatic duct to 3.3 (1.3-10.4) for accessory ducts. Increased body mass index was associated with reduced detection of most structures in both groups, especially before dissection. Only 2 patients, both in the WL group, sustained a biliary duct injury. CONCLUSIONS: In a randomized controlled trial, NIFC was statistically superior to WL alone visualizing extrahepatic biliary structures during laparoscopic cholecystectomy. REGISTRATION NUMBER: NCT02702843.

Passive force and viscoelastic properties of single fibers in human aging muscles.

PURPOSE: Changes in stiffness or extensibility of the muscle or muscle-tendon unit with aging could lead to impaired function and an increased vulnerability to injury. We aimed to investigate the passive force and viscoelastic properties of single muscle fibers in older adults. METHODS: Seven older adults (mean age 79.0 ± 3.8 years) and 10 young control (mean age 25.6 ± 4.5 years) were recruited. Biopsy specimens were obtained percutaneously from m. vastus lateralis and skinned single fibers were used for the experiments. Slack tests were performed to determine maximal force and maximal unloaded shortening velocity. Passive force was measured in pCa 9.0 solution using a stepwise stretch technique with increment of sarcomere length from 2.4 to 4.2 µm. Myosin heavy chain (MHC) isoform was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Specific force was calculated as maximal force divided by cross-sectional area. Passive force, peak passive force, time to half stress relaxation (T1/2) and force decay index (a force time integral under a stress relaxation curve) were measured. RESULTS: No difference between the groups were found in specific force and shortening velocity. Passive force and peak passive force were greater in both MHC I and IIa fibers of older adults (p < 0.001, p = 0.012, respectively, at 4.2 mm SL). Force decay index was higher in older adults. (p = 0.001 at 4.2 µm SL). There were no significant differences in passive force and viscoelastic properties between fiber types. CONCLUSION: We demonstrated greater passive force and viscoelastic properties at the level of single fibers in older adults.

Preventing Type 2 Diabetes with Home Cooking: Current Evidence and Future Potential.

PURPOSE OF REVIEW: Various dietary regimes have proven effective in preventing diabetes, yet its prevalence is growing. This review's goals are to examine the relationship between home cooking and diabetes and to present the literature on home cooking education programs as a novel strategy to improve adherence to healthy nutrition, thus decreasing the risk of diabetes. RECENT FINDINGS: Consumption of home-cooked food is linked to healthier nutrition and decreased risk of diabetes. Further, home cooking interventions have a short-term positive impact on nutritional intake of both children and adults, and on diabetes prevention. Well-designed randomized controlled studies are needed to rigorously evaluate the long-term impact of home cooking interventions on cooking behavior, dietary intake, diabetes, and healthcare costs. Culinary education is an emerging field that aims to change nutrition education paradigms. Clinicians can empower patients to adopt home cooking by role modeling home cooking themselves, including home cooking content in their medical encounters, and through comprehensive lifestyle medicine interventions.

Evaluation of Clinical Prognostic Factors and Further Delineation of the Effect of Mesenteric Fibrosis on Survival in Advanced Midgut Neuroendocrine Tumours.

BACKGROUND: Small intestinal neuroendocrine tumours (SI NETs) represent 30-50% of small bowel neoplasms and often present at an advanced stage. To date, there is relatively limited literature regarding prognostic factors affecting overall survival (OS) in stage IV disease. In addition, the prevalence of mesenteric fibrosis (MF) in SI NETs and its effect on OS have not been sufficiently explored in the literature. AIM: The primary aim of this study was to perform a large-scale survival analysis in an institutional cohort of 387 patients with metastatic (stage IV) SI NETs. The secondary aim was to provide epidemiological information regarding the prevalence of MF and to evaluate its effect on OS. RESULTS: The median OS was 101 months (95% CI 84, 118). Age > 65 years, mesenteric metastases with and without desmoplasia, liver metastases, carcinoid heart disease (CHD) and bone metastases were associated with a significantly shorter OS, while primary tumour resection was predictive of a longer OS. The benefit of surgical resection was limited to symptomatic patients. MF was present in approximately 50% of patients with mesenteric lymphadenopathy. Elevated urinary 5-HIAA levels correlated strongly with the presence of CHD (p < 0.001) and to a lesser extent (p = 0.02) with MF. MF and CHD did not usually co-exist, suggesting that different mechanisms are likely to be involved in the development of these fibrotic complications. CONCLUSIONS: This study has identified specific prognostic factors in a large cohort of 387 patients with advanced SI NETs and has provided useful epidemiological data regarding carcinoid-related fibrotic complications.

Motor and Sensory Deficits in the teetering Mice Result from Mutation of the ESCRT Component HGS.

Neurons are particularly vulnerable to perturbations in endo-lysosomal transport, as several neurological disorders are caused by a primary deficit in this pathway. In this report, we used positional cloning to show that the spontaneously occurring neurological mutation teetering (tn) is a single nucleotide substitution in hepatocyte growth factor-regulated tyrosine kinase substrate (Hgs/Hrs), a component of the endosomal sorting complex required for transport (ESCRT). The tn mice exhibit hypokenesis, muscle weakness, reduced muscle size and early perinatal lethality by 5-weeks of age. Although HGS has been suggested to be essential for the sorting of ubiquitinated membrane proteins to the lysosome, there were no alterations in receptor tyrosine kinase levels in the central nervous system, and only a modest decrease in tropomyosin receptor kinase B (TrkB) in the sciatic nerves of the tn mice. Instead, loss of HGS resulted in structural alterations at the neuromuscular junction (NMJ), including swellings and ultra-terminal sprouting at motor axon terminals and an increase in the number of endosomes and multivesicular bodies. These structural changes were accompanied by a reduction in spontaneous and evoked release of acetylcholine, indicating a deficit in neurotransmitter release at the NMJ. These deficits in synaptic transmission were associated with elevated levels of ubiquitinated proteins in the synaptosome fraction. In addition to the deficits in neuronal function, mutation of Hgs resulted in both hypermyelinated and dysmyelinated axons in the tn mice, which supports a growing body of evidence that ESCRTs are required for proper myelination of peripheral nerves. Our results indicate that HGS has multiple roles in the nervous system and demonstrate a previously unanticipated requirement for ESCRTs in the maintenance of synaptic transmission.

Single-stage revision from gastric band to gastric bypass or sleeve gastrectomy: 6- and 12-month outcomes.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is increasingly requiring revisional surgery for complications and failures. Removal of the band and conversion to either laparoscopic Roux-en-y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) is feasible as a single-stage procedure. The objective of this study is to compare the safety and efficacy of single-stage revision from LAGB to either LRYGB or LSG at 6 and 12 months postoperatively. METHODS: Retrospective analysis was performed on patients undergoing single-stage revision between 2009 and 2014 at a single academic medical center. Patients were reassessed for weight loss and complications at 6 and 12 months postoperatively. RESULTS: Thirty-two patients underwent single-stage revision to LRYGB, and 72 to LSG. Preoperative BMIs were similar between the two groups (p = 0.27). Median length of stay for LRYGB was 3 days versus 2 for LSG (p = 0.14). Four patients in the LRYGB group required reoperation within 30 days, and two patients in the LSG group required reoperation within 30 days (p = 0.15). There was no difference in ER visits (p = 0.24) or readmission rates (p = 0.80) within 30 days of operation. Six delayed complications were seen in the LSG group with three requiring intervention. At 6 months postoperatively, percent excess weight loss (%EWL) was 50.20 for LRYGB and 30.64 for LSG (p = 0.056). At 12 months, %EWL was 51.19 for LRYGB and 34.89 for LSG (p = 0.31). There was no difference in diabetes or hypertension medication reduction at 12 months between LRYGB and LSG (p > 0.07). CONCLUSION: Single-stage revision from LAGB to LRYGB or LSG is technically feasible, but not without complications. The complications in the bypass group were more severe. There was no difference in readmission or reoperation rates, weight loss or comorbidity reduction. Revision to LRYGB trended toward higher rate and greater severity of complications with equivalent weight loss and comorbidity reduction.

Serum Predictors of Percent Lean Mass in Young Adults.

Lustgarten, MS, Price, LL, Phillips, EM, Kirn, DR, Mills, J, and Fielding, RA. Serum predictors of percent lean mass in young adults. J Strength Cond Res 30(8): 2194-2201, 2016-Elevated lean (skeletal muscle) mass is associated with increased muscle strength and anaerobic exercise performance, whereas low levels of lean mass are associated with insulin resistance and sarcopenia. Therefore, studies aimed at obtaining an improved understanding of mechanisms related to the quantity of lean mass are of interest. Percent lean mass (total lean mass/body weight × 100) in 77 young subjects (18-35 years) was measured with dual-energy x-ray absorptiometry. Twenty analytes and 296 metabolites were evaluated with the use of the standard chemistry screen and mass spectrometry-based metabolomic profiling, respectively. Sex-adjusted multivariable linear regression was used to determine serum analytes and metabolites significantly (p ≤ 0.05 and q ≤ 0.30) associated with the percent lean mass. Two enzymes (alkaline phosphatase and serum glutamate oxaloacetate aminotransferase) and 29 metabolites were found to be significantly associated with the percent lean mass, including metabolites related to microbial metabolism, uremia, inflammation, oxidative stress, branched-chain amino acid metabolism, insulin sensitivity, glycerolipid metabolism, and xenobiotics. Use of sex-adjusted stepwise regression to obtain a final covariate predictor model identified the combination of 5 analytes and metabolites as overall predictors of the percent lean mass (model R = 82.5%). Collectively, these data suggest that a complex interplay of various metabolic processes underlies the maintenance of lean mass in young healthy adults.

From a Vital Sign to Vitality: Selling Exercise So Patients Want to Buy It.

Exercise is Medicine (EIM) and physical activity as a vital sign are based on health-focused research and reflect ideal frames and messages for clinicians. However, they are nonoptimal for patients because they do not address what drives patients' decision-making and motivation. With the growing national emphasis on patient-centered and value-based care, it is the perfect time for EIM to evolve and advance a second-level consumer-oriented exercise prescription and communication strategy. Through research on decision-making, motivation, consumer behavior, and meaningful goal pursuit, this article features six evidence-based issues to help clinicians make physical activity more relevant and compelling for patients to sustain in ways that concurrently support patient-centered care. Physical activity prescriptions and counseling can evolve to reflect affective and behavioral science and sell exercise so patients want to buy it.