Effect of Remotely Supervised Weight Loss and Exercise Training Versus Lifestyle Counseling on Cardiovascular Risk and Clinical Outcomes in Older Adults With Rheumatoid Arthritis: A Randomized Controlled Trial.

OBJECTIVE: To compare a remotely supervised weight loss and exercise intervention to lifestyle counseling for effects on cardiovascular disease risk, disease activity, and patient-reported outcomes in older patients with rheumatoid arthritis (RA) and overweight/obesity. METHODS: Twenty older (60-80 years), previously sedentary participants with seropositive RA and overweight/obesity were randomized to 16 weeks of either Supervised Weight loss and Exercise Training (SWET) or Counseling Health As Treatment (CHAT). The SWET group completed aerobic training (150 minutes/week moderate-to-vigorous intensity), resistance training (two days/week), and a hypocaloric diet (7% weight loss goal). The CHAT control group completed two lifestyle counseling sessions followed by monthly check-ins. The primary outcome was a composite metabolic syndrome z-score (MSSc) derived from fasting glucose, triglycerides, high density lipoprotein-cholesterol, minimal waist circumference, and mean arterial pressure. Secondary outcomes included RA disease activity and patient-reported outcomes. RESULTS: Both groups improved MSSc (absolute change -1.67 ± 0.64 in SWET; -1.34 ± 1.30 in CHAT; P < 0.01 for both groups) with no between-group difference. Compared with CHAT, SWET significantly improved body weight, fat mass, Disease Activity Score-28 C-reactive protein, and patient-reported physical health, physical function, mental health, and fatigue (P < 0.04 for all between-group comparisons). Based on canonical correlations for fat mass, cardiorespiratory fitness, and leg strength, component-specific effects were strongest for (1) weight loss improving MSSc, physical health, and mental health; (2) aerobic training improving physical function and fatigue; and (3) resistance training improving Disease Activity Score-28 C-reactive protein. CONCLUSION: In older patients with RA and overweight/obesity, 16 weeks of remotely supervised weight loss, aerobic training, and resistance training improve cardiometabolic health, patient-reported outcomes, and disease activity. Less intensive lifestyle counseling similarly improves cardiovascular disease risk profiles, suggesting an important role for integrative interventions in the routine clinical care of this at-risk RA population.

Effects of exercise amount and intensity versus a combined exercise and lifestyle intervention on metabolic syndrome in adults with prediabetes: a STRRIDE-PD randomized trial.

The purpose of this secondary analysis was to determine what portion of the effects of a Diabetes Prevention Program-like intervention on metabolic syndrome (MetS) could be achieved with exercise alone, as well as to determine the relative importance of exercise intensity and amount to the total exercise effect on MetS. Sedentary, overweight adults with prediabetes were randomly assigned to one of four 6-month interventions: 1) low-amount/moderate-intensity (10 kcal/kg/week at 50% peak V˙O2); 2) high-amount/moderate-intensity (16 kcal/kg/week at 50% peak V˙O2); 3) high-amount/vigorous-intensity (16 kcal/kg/week at 75% peak V˙O2); or 4) diet (7% weight loss) plus low-amount/moderate-intensity (10 kcal/kg/week at 50% peak V˙O2). The primary outcome of this secondary analysis was change in the MetS z-score. A total of 130 participants had complete data for all five Adult Treatment Panel (ATP) III MetS criteria. The diet-and-exercise group statistically outperformed the MetS z-score and the ATP III score compared to the exercise alone group. Aerobic exercise alone achieved 24%-50% of the total effect of the combined diet-and-exercise intervention on the MetS score. Low-amount moderate-intensity exercise quantitatively performed equal to or better than the interventions of high-amount moderate-intensity or high-amount vigorous-intensity exercise in improving the MetS score. The combined diet-and-exercise intervention remains more efficacious in improving the MetS z-score. However, all three exercise interventions alone showed improvements in the MetS z-score, suggesting that a modest amount of moderate-intensity exercise is all that is required to achieve approximately half the effect of a diet-and-exercise intervention on the MetS. Clinical Trial Registration: clinicaltrials.gov, identifier NCT00962962.

Multimodality annotated hepatocellular carcinoma data set including pre- and post-TACE with imaging segmentation.

Hepatocellular carcinoma (HCC) is the most common primary liver neoplasm, and its incidence has doubled over the past two decades owing to increasing risk factors. Despite surveillance, most HCC cases are diagnosed at advanced stages and can only be treated using transarterial chemo-embolization (TACE) or systemic therapy. TACE failure may occur with incidence reaching up to 60% of cases, leaving patients with a financial and emotional burden. Radiomics has emerged as a new tool capable of predicting tumor response to TACE from pre-procedural computed tomography (CT) studies. This data report defines the HCC-TACE data collection of confirmed HCC patients who underwent TACE and have pre- and post-procedure CT imaging studies and available treatment outcomes (time-to-progression and overall survival). Clinically curated segmentation of pre-procedural CT studies was done for the purpose of algorithm training for prediction and automatic liver tumor segmentation.

Comparison of early post-operative complications in primary and revisional laparoscopic sleeve gastrectomy, gastric bypass, and duodenal switch MBSAQIP-reported cases from 2015 to 2019.

BACKGROUND: Sleeve gastrectomy (SG) is now the most performed bariatric surgery, though gastric bypass (GB) and duodenal switch (DS) remain common, especially as conversion/revision (C/R) procedures. This analysis compared early postoperative outcomes of primary and C/R laparoscopic SG to DS and GB; and primary procedures of each vs C/R counterparts. METHODS: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) dataset was queried for SG, GB, and DS cases from 2015 to 2019. Multivariable logistic regression calculated crude and adjusted odds ratios for surgical site infection (SSI), reoperation, and readmission at 30 days in two initial comparisons: (1) primary SG vs DS or GB and (2) C/R SG vs DS or GB. A secondary analysis compared primary GS, GB, or DS with C/R counterparts. Models were adjusted for confounding demographics and comorbidities. RESULTS: Of 755,968 primary cases, most were SG (72.8%), followed by GB (26.3%), then DS (0.9%). Compared to SG, GB and DS demonstrated higher odds of SSI (aOR 3.02 [2.84, 3.2]), readmission (aOR 1.97 [1.92, 2.03]), and reoperation (aOR 2.74 [2.62, 2.86]), respectively. Of 68,716 C/R cases, SG was most common (43.2%), followed by GB (37.5%), then DS (19.2%). C/R GB and DS demonstrated greater risk of SSI (aOR 2.28 [1.98, 2.62]), readmission (aOR 2.10 [1.94, 2.27]), and reoperation (aOR 2.3 [2.04, 2.59]) vs SG, respectively. C/R SG and DS demonstrated greater risk of SSI (OR 2.09 [1.66, 2.63]; 1.63 [1.24, 2.14), readmission (OR 1.13 [1.02, 1.26]), and reoperation (OR 1.27 [1.06, 1.52]; 1.58 [1.24, 2.0]), vs primary procedures. C/R DS demonstrated greater risk of SSI (OR 1.23 [1.66, 2.63]). CONCLUSIONS: Early complications are comparable between GB and DS, and greater than SG. In C/R procedures, GB and DS demonstrate greater risk than SG. Overall, C/R procedures demonstrate greater risk of most, but not all, early postoperative complications.

Comparison of robot-assisted sleeve gastrectomy outcomes in multiple staple line treatment modalities from 2015 to 2019: a 5-year propensity score-adjusted MBSAQIP® analysis.

BACKGROUND: Robot-assisted sleeve gastrectomy (RSG) is an increasingly common approach to sleeve gastrectomy (SG). Staple line reinforcement (SLR) is well-discussed in laparoscopic SG literature, but not RSG- likely due to the absence of dedicated robotic SLR devices. However, most RSG cases report SLR. This retrospective analysis compares outcomes in RSG cases reporting (1) any staple line treatment (SLT) vs none and (2) SLR vs oversewing. METHODS: MBSAQIP was queried for adults who underwent RSG from 2015 to 2019. Open procedures, Natural Orifice Transluminal Endoscopic Surgery, hand-assisted, single-incision, concurrent procedures, and illogical BMIs were excluded (n = 3444). Final sample included 52,354 patients. Two comparisons were made: SLT (n = 34,886) vs none (n = 17,468) and SLR (n = 22,217) vs oversew (n = 5620). We fitted multivariable regression models to estimate risk ratios (RR) and 95% confidence intervals (CI) and performed propensity score analysis with inverse probability of treatment weight based on patient factors. RESULTS: Most RSG cases utilized SLT (66.6%). Cases with SLT had a reduced risk of organ space SSI (RR 0.68 [0.49, 0.94]), 30-day reoperation (RR 0.77 [0.64, 0.93]), 30-day re-intervention (RR 0.80 [0.67, 0.96]), sepsis (RR 0.58 [0.35, 0.96]), unplanned intubation (RR 0.59 [0.37, 0.93]), extended ventilator use (RR 0.46 [0.23, 0.91]), and renal failure (RR 0.40 [0.19, 0.82]) compared to no-treatment cases. In single-treatment cases (n = 27,837), most utilized SLR (79.8%). Cases with oversew had a higher risk of any SSI (RR 1.70 [1.19, 2.42]), superficial incisional SSI (RR 1.71 [1.06, 2.76]), septic shock (RR 6.47 [2.11, 19.87]), unplanned intubation (RR 2.18 [1.06, 4.47]), and extended ventilator use (> 48 h) (RR 4.55 [1.63, 12.71]) than SLR. CONCLUSIONS: Our data suggest SLT in RSG is associated with reduced risk of some adverse outcomes vs no-treatment. Among SLT, SLR demonstrated lower risk than oversewing. However, risk of all-cause mortality, cardiac arrest, and unplanned ICU admission were not significant.

Infective Endocarditis-Associated Pauci-Immune Glomerulonephritis in a Patient With Cryoglobulinemia.

Small-vessel vasculitis has a broad differential with similar clinical presentation and laboratory abnormalities, including petechial rashes, neurologic symptoms, glomerulonephritis, and abnormal inflammatory markers. Biopsy-based diagnosis is critical as the treatment varies by etiology. We report a case of a 41-year-old man with diagnosed cryoglobulinemia and hepatitis C presenting with a petechial rash, altered mental status, and acute kidney injury and ultimately found to have proteinase 3 (PR3)-antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis secondary to infective endocarditis. Skin biopsy was consistent with resolving, but nonspecific vasculitis and MRI showed foci of hemosiderin deposition concerning vasculitic lesions. Blood cultures grew Enterococcus faecalis, and he was treated with IV antibiotics. Kidney biopsy showed pauci-immune necrotizing focal segmental glomerulonephritis (GN) and diffuse acute tubular necrosis (ATN). After blood cultures cleared, he was initially treated with mycophenolate for worsening renal function. When the patient stopped antibiotics unexpectedly, his kidney function worsened and improved only after immunosuppression was stopped and antibiotics were restarted. This case highlights the importance of renal biopsy in patients with multiple potential etiologies of GN. The case resolution also reinforces that patients with infective endocarditis causing ANCA-associated GN should be treated with antibiotics in addition to, and possibly instead of, immunosuppression.

Identification of an ATP/P2X7/mast cell pathway mediating ozone-induced bronchial hyperresponsiveness.

Ozone is a highly reactive environmental pollutant with well-recognized adverse effects on lung health. Bronchial hyperresponsiveness (BHR) is one consequence of ozone exposure, particularly for individuals with underlying lung disease. Our data demonstrated that ozone induced substantial ATP release from human airway epithelia in vitro and into the airways of mice in vivo and that ATP served as a potent inducer of mast cell degranulation and BHR, acting through P2X7 receptors on mast cells. Both mast cell-deficient and P2X7 receptor-deficient (P2X7-/-) mice demonstrated markedly attenuated BHR to ozone. Reconstitution of mast cell-deficient mice with WT mast cells and P2X7-/- mast cells restored ozone-induced BHR. Despite equal numbers of mast cells in reconstituted mouse lungs, mice reconstituted with P2X7-/- mast cells demonstrated significantly less robust BHR than mice reconstituted with WT mast cells. These results support a model where P2X7 on mast cells and other cell types contribute to ozone-induced BHR.

Cardiopulmonary Exercise Testing in the Coronavirus Disease - 2019 Era: Safety and Protocol Considerations.

ABSTRACT: Cardiopulmonary exercise testing (CPX) is a valuable tool in both clinical practice and research settings. Therefore, it is advantageous for human performance laboratories to continue operating during the coronavirus disease 2019 (COVID-19) pandemic. All institutions should adhere to general COVID-19 guidelines provided by the Centers for Disease Control. Because of the testing environment, CPX laboratories must consider additional precautionary safety measures. This article provides recommendations for modifying the CPX protocol to ensure safety for all stakeholders during the pandemic. These modifications are universal across all populations, types of institutions and testing modalities. Preliminary measures include careful review of federal, local, and institutional mandates. The description outlines how to evaluate a testing environment and alter workflow. Guidelines are provided on what specific personal protective equipment should be acquired; as well as necessary actions before, during, and after the CPX test. These precautions will limit the possibility of both clients and staff from contracting or spreading the disease while maintaining testing volume in the laboratory.

Recent Trends in Cardiothoracic Surgery Training: Data from the National Resident Matching Program.

OBJECTIVE: In 2008, integrated thoracic residency programs (IP) for cardiothoracic (CT) training were created in response to a decline in CT trainees. However, few studies have reported on trends in the CT training pathway since the inception of IPs. This manuscript examines the current trends related to the overall number of surgical trainees entering CT surgery training following the introduction of IPs into the National Resident Match Program (NRMP). DESIGN: Main and specialty match data were gathered from NRMP annual reports between 2008 and 2018. Descriptive statistics were used to analyze program size, applications, and filled and unfilled positions for IPs and traditional CT residency programs. Pearson's correlation coefficient was used to determine associations between program variables. SETTING: NRMP main and specialty match in 2008 to 2018. PARTICIPANTS: Participants of the NRMP main and specialty match in 2008 to 2018. RESULTS: IPs increased from 2 programs offering 3 positions in 2008 to 28 programs offering 36 positions in 2018. However, during the same time period, the number of available traditional CT residency positions have decreased by 29% (130 to 92). As the number of IPs increased, there was a significant decrease in the number of traditional CT residency positions (ρ = -0.95, p < 0.001). Although, the overall number of CT residency programs (traditional and IP) remained largely unchanged, the proportion of filled CT residency positions increased from 67.7% in 2008 up to 97.7% in 2018. CONCLUSION: The IP training format has shown success in increasing the number of trainees entering into CT training programs. Consideration should be given to increasing the number of IP positions or increase interest in CT among general surgery residents to increase the number of CT surgery trainees with the goal of increasing the size of the future CT workforce.

Pain Agreements and Time-to-Event Analysis of Substance Misuse in a Primary Care Chronic Pain Program.

BACKGROUND: Types and correlates of pain medication agreement (PMA) violations in the primary care setting have not been analyzed. METHODS: A retrospective analysis was completed to examine patient characteristics and correlates of PMA violations, a proxy for substance misuse, over a 15-year period in an outpatient General Medicine Pain Service within the Division of General Medicine and Clinical Epidemiology, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill. Patients who signed the PMA were managed for chronic pain from 2002 through 2017 (N = 1,210). The incidence of PMA violations was measured over a 15-year span. Substance misuse was defined a priori in the study as urine toxicology screen positive for illicit or nonprescribed controlled substances, patient engagement in prescription alteration, doctor-shopping, or diversion. RESULTS: Most patients received a prescription for a controlled substance (77.4%). During enrollment, 488 (40.3%) patients had one or more violations of their PMA. One-third (33.4%) of pain service patients had a violation within 365 days of signing the agreement. Active tobacco smokers had double the incidence of agreement violation within the first 30 days of enrollment. Almost one-half (49.8%) of violations were due to inconsistent use of controlled substances. Patients with any prior DWI/DUI or drug-related offense had a significantly increased rate of substance misuse (P < 0.0001). CONCLUSIONS: PMA violations were common among a population of patients managed for chronic nonmalignant pain. Universal opioid prescribing precautions, including PMAs, require further investigation to assess their roles in mitigating the potential patient and societal harms associated with opioid prescribing.

Author Correction: Imaging and clinical data archive for head and neck squamous cell carcinoma patients treated with radiotherapy.

In the original version of the Data Descriptor the surname of author Hesham Elhalawani was misspelled. This has now been corrected in the HTML and PDF versions.

Imaging and clinical data archive for head and neck squamous cell carcinoma patients treated with radiotherapy.

Cross sectional imaging is essential for the patient-specific planning and delivery of radiotherapy, a primary determinant of head and neck cancer outcomes. Due to challenges ensuring data quality and patient de-identification, publicly available datasets including diagnostic and radiation treatment planning imaging are scarce. In this data descriptor, we detail the collection and processing of computed tomography based imaging in 215 patients with head and neck squamous cell carcinoma that were treated with radiotherapy. Using cross sectional imaging, we calculated total body skeletal muscle and adipose content before and after treatment. We detail techniques for validating the high quality of these data and describe the processes of data de-identification and transfer. All imaging data are subject- and date-matched to clinical data from each patient, including demographics, risk factors, grade, stage, recurrence, and survival. These data are a valuable resource for studying the association between patient-specific anatomic and metabolic features, treatment planning, and oncologic outcomes, and the first that allows for the integration of body composition as a risk factor or study outcome.

Heparan Sulfate Binding Promotes Accumulation of Intravitreally Delivered Adeno-associated Viral Vectors at the Retina for Enhanced Transduction but Weakly Influences Tropism.

Many adeno-associated virus (AAV) serotypes efficiently transduce the retina when delivered to the subretinal space but show limited success when delivered to the vitreous due to the inner limiting membrane (ILM). Subretinal delivery of AAV serotype 2 (AAV2) and its heparan sulfate (HS)-binding-deficient capsid led to similar expression, indicating transduction of the outer retina occurred by HS-independent mechanisms. However, intravitreal delivery of HS-ablated recombinant AAV2 (rAAV2) led to a 300-fold decrease in transduction compared to AAV2. Fluorescence in situ hybridization of AAV transgenes was used to identify differences in retinal trafficking and revealed that HS binding was responsible for AAV2 accumulation at the ILM. This mechanism was tested on human ex vivo retinas and showed similar accumulation with HS-binding AAV2 capsid only. To evaluate if HS binding could be applied to other AAV serotypes to enhance their transduction, AAV1 and AAV8 were modified to bind HS with a single-amino-acid mutation and tested in mice. Both HS-binding mutants of AAV1 and AAV8 had higher intravitreal transduction than their non-HS-binding parent capsid due to increased retinal accumulation. To understand the influence that HS binding has on tropism, chimeric AAV2 capsids with dual-glycan usage were tested intravitreally in mice. Compared to HS binding alone, these chimeric capsids displayed enhanced transduction that was correlated with a change in tropism. Taken together, these data indicate that HS binding serves to sequester AAV capsids from the vitreous to the ILM but does not influence retinal tropism. The enhanced retinal transduction of HS-binding capsids provides a rational design strategy for engineering capsids for intravitreal delivery. IMPORTANCE: Adeno-associated virus (AAV) has become the vector of choice for viral gene transfer and has shown great promise in clinical trials. The need for development of an easy, less invasive injection route for ocular gene therapy is met by intravitreal delivery, but delivery of AAV by this route results in poor transduction outcomes. The inner limiting membrane (ILM) creates a barrier separating the vitreous and the retina. Binding of AAV to heparan sulfate proteoglycan (HSPG) at the ILM may allow the virus to traverse this barrier for better retinal transduction. We show that HSPG binding is correlated with greater accumulation and penetration of AAV in the retina. We demonstrated that this accumulation is conserved across mouse and human retinas and that the addition of HSPG binding to other AAV capsids can increase the number of vectors accumulating at the ILM without dictating tropism.