Tumour exosome integrins determine organotropic metastasis.

Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6ß4 and α6ß1 were associated with lung metastasis, while exosomal integrin αvß5 was linked to liver metastasis. Targeting the integrins α6ß4 and αvß5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

Implementing a pharmacist-integrated collaborative model of medication treatment for opioid use disorder in primary care: study design and methodological considerations.

BACKGROUND: Pharmacists remain an underutilized resource in the treatment of opioid use disorder (OUD). Although studies have engaged pharmacists in dispensing medications for OUD (MOUD), few studies have evaluated collaborative care models in which pharmacists are an active, integrated part of a primary care team offering OUD care. METHODS: This study seeks to implement a pharmacist integrated MOUD clinical model (called PrIMO) and evaluate its feasibility, acceptability, and impact across four diverse primary care sites. The Consolidated Framework for Implementation Research is used as an organizing framework for study development and interpretation of findings. Implementation Facilitation is used to support PrIMO adoption. We assess the primary outcome, the feasibility of implementing PrIMO, using the Stages of Implementation Completion (SIC). We evaluate the acceptability and impact of the PrIMO model at the sites using mixed-methods and combine survey and interview data from providers, pharmacists, pharmacy technicians, administrators, and patients receiving MOUD at the primary care sites with patient electronic health record data. We hypothesize that it is feasible to launch delivery of the PrIMO model (reach SIC Stage 6), and that it is acceptable, will positively impact patient outcomes 1 year post model launch (e.g., increased MOUD treatment retention, medication regimen adherence, service utilization for co-morbid conditions, and decreased substance use), and will increase each site's capacity to care for patients with MOUD (e.g., increased number of patients, number of prescribers, and rate of patients per prescriber). DISCUSSION: This study will provide data on a pharmacist-integrated collaborative model of care for the treatment of OUD that may be feasible, acceptable to both site staff and patients and may favorably impact patients' access to MOUD and treatment outcomes. TRIAL REGISTRATION: The study was registered on Clinicaltrials.gov (NCT05310786) on April 5, 2022, https://www. CLINICALTRIALS: gov/study/NCT05310786?id=NCT05310786&rank=1.

Surgical Management of Hidradenitis Suppurativa: A Two-Center Retrospective Study.

BACKGROUND: Hidradenitis suppurativa is a chronic inflammatory condition that presents a challenging reconstructive problem for plastic surgeons. METHODS: The authors performed a retrospective chart review of hidradenitis suppurativa patients managed with surgical excision between 2005 and 2020 at Brigham and Women's Hospital and Tulane University Medical Center. Operative cases associated with the same hospitalization were organized into treatment episodes and assessed for patient demographics, operative techniques, and outcomes. RESULTS: A total of 181 patients, 435 cases and 316 treatment episodes (Brigham and Women's Hospital, n = 269; Tulane University Medical Center, n = 47), were identified across two diverse institutions. Their respective series showed comparable patient demographics, and 94 percent of the combined episodes achieved wound closure and healing during the study period. Several techniques of closure were identified, including immediate closure and site-specific methods, such as an expedited staged closure using internal negative-pressure wound therapy as a temporary bridge, "recycled" skin grafting, and repurposing iodoform wicks as an adjunct wound healing therapy to immediate closure. CONCLUSIONS: This large multi-institutional retrospective chart review on the plastic surgical management of hidradenitis suppurativa demonstrates that surgery is an effective therapy for hidradenitis suppurativa and captures a diversity of site-specific techniques that may serve as a foundation for future prospective studies and evidence-based guidelines for the use of various techniques to optimize patients' surgical outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Plastic Surgical Management of Hidradenitis Suppurativa.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Describe the pathogenesis of hidradenitis suppurativa. 2. Discuss perioperative multimodal therapy of hidradenitis suppurativa, including medical optimization. 3. Determine an appropriate surgical plan with excision and reconstruction based on hidradenitis suppurativa severity, size, and anatomical location. SUMMARY: Successful treatment of hidradenitis suppurativa requires a multidisciplinary team approach and multimodal therapy.

Effects of aerobic and resistance training on hemoglobin A1c levels in patients with type 2 diabetes: a randomized controlled trial.

CONTEXT: Exercise guidelines for individuals with diabetes include both aerobic and resistance training although few studies have directly examined this exercise combination. OBJECTIVE: To examine the benefits of aerobic training alone, resistance training alone, and a combination of both on hemoglobin A(1c) (HbA(1c)) in individuals with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: A randomized controlled trial in which 262 sedentary men and women in Louisiana with type 2 diabetes and HbA(1c) levels of 6.5% or higher were enrolled in the 9-month exercise program between April 2007 and August 2009. INTERVENTION: Forty-one participants were assigned to the nonexercise control group, 73 to resistance training 3 days a week, 72 to aerobic exercise in which they expended 12 kcal/kg per week; and 76 to combined aerobic and resistance training in which they expended 10 kcal/kg per week and engaged in resistance training twice a week. Main Outcome Change in HbA(1c) level. Secondary outcomes included measures of anthropometry and fitness. RESULTS: The study included 63.0% women and 47.3% nonwhite participants who were a mean (SD) age of 55.8 years (8.7 years) with a baseline HbA(1c) level of 7.7% (1.0%). Compared with the control group, the absolute mean change in HbA(1c) in the combination training exercise group was -0.34% (95% confidence interval [CI], -0.64% to -0.03%; P = .03). The mean changes in HbA(1c) were not statistically significant in either the resistance training (-0.16%; 95% CI, -0.46% to 0.15%; P = .32) or the aerobic (-0.24%; 95% CI, -0.55% to 0.07%; P = .14) groups compared with the control group. Only the combination exercise group improved maximum oxygen consumption (mean, 1.0 mL/kg per min; 95% CI, 0.5-1.5, P < .05) compared with the control group. All exercise groups reduced waist circumference from -1.9 to -2.8 cm compared with the control group. The resistance training group lost a mean of -1.4 kg fat mass (95% CI, -2.0 to -0.7 kg; P < .05) and combination training group lost a mean of -1.7 (-2.3 to -1.1 kg; P < .05) compared with the control group. CONCLUSIONS: Among patients with type 2 diabetes mellitus, a combination of aerobic and resistance training compared with the nonexercise control group improved HbA(1c) levels. This was not achieved by aerobic or resistance training alone. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00458133.

Aerobic and strength training in concomitant metabolic syndrome and type 2 diabetes.

PURPOSE: Concomitant type 2 diabetes (T2D) and metabolic syndrome exacerbates mortality risk; yet, few studies have examined the effect of combining (AER + RES) aerobic (AER) and resistance (RES) training for individuals with T2D and metabolic syndrome. METHODS: We examined AER, RES, and AER + RES training (9 months) commensurate with physical activity guidelines in individuals with T2D (n = 262; 63% female, 44% black). Primary outcomes were change in, and prevalence of, metabolic syndrome score at follow-up (mean and 95% confidence interval [CI]). Secondary outcomes included maximal cardiorespiratory fitness (VO2peak) and estimated METs from time-to-exhaustion (TTE) and exercise efficiency calculated as the slope of the line between ventilatory threshold, respiratory compensation, and maximal fitness. General linear models and bootstrapped Spearman correlations were used to examine changes in metabolic syndrome associated with training primary and secondary outcome variables. RESULTS: We observed a significant decrease in metabolic syndrome scores (P for trend = 0.003) for AER (-0.59, 95% CI = -1.00 to -0.21) and AER + RES (-0.79, 95% CI = -1.40 to -0.35), both being significant (P ≤ 0.02) versus control (0.26, 95% CI = -0.58 to 0.40) and RES (-0.13, 95% CI = -1.00 to 0.24). This led to a reduction in metabolic syndrome prevalence for the AER (56% vs 43%) and AER + RES (55% vs 46%) groups between baseline and follow-up. The observed decrease in metabolic syndrome was mediated by significant improvements in exercise efficiency for the AER and AER + RES training groups (P < 0.05), which was more strongly related to TTE (25%-30%; r = -0.38, 95% CI = -0.55 to -0.19) than VO2peak (5%-6%; r = -0.24, 95% CI = -0.45 to -0.01). CONCLUSIONS: AER and AER + RES training significantly improved metabolic syndrome scores and prevalence in patients with T2D. These improvements appear to be associated with improved exercise efficiency and are more strongly related to improved TTE versus VO2peak.

Exercise training and quality of life in individuals with type 2 diabetes: a randomized controlled trial.

OBJECTIVE: To establish whether exercise improves quality of life (QOL) in individuals with type 2 diabetes and which exercise modalities are involved. RESEARCH DESIGN AND METHODS: Health Benefits of Aerobic and Resistance Training in individuals with type 2 Diabetes (HART-D; n = 262) was a 9-month exercise study comparing the effects of aerobic training, resistance training, or a combination of resistance and aerobic training versus a nonexercise control group on hemoglobin A1c (HbA1c) in sedentary individuals with type 2 diabetes. This study is an ancillary analysis that examined changes in QOL after exercise training using the Short Form-36 Health Survey questionnaire compared across treatment groups and with U.S. national norms. RESULTS: The ancillary sample (n = 173) had high baseline QOL compared with U.S. national norms. The QOL physical component subscale (PCS) and the general health (GH) subscale were improved by all three exercise training conditions compared with the control group condition (resistance: PCS, P = 0.005; GH, P = 0.003; aerobic: PCS, P = 0.001; GH, P = 0.024; combined: PCS, P = 0.015; GH, P = 0.024). The resistance training group had the most beneficial changes in bodily pain (P = 0.026), whereas physical functioning was most improved in the aerobic and combined condition groups (P = 0.025 and P = 0.03, respectively). The changes in the mental component score did not differ between the control group and any of the exercise groups (all P > 0.05). The combined training condition group had greater gains than the aerobic training condition group in the mental component score (P = 0.004), vitality (P = 0.031), and mental health (P = 0.008) and greater gains in vitality compared with the control group (P = 0.021). CONCLUSIONS: Exercise improves QOL in individuals with type 2 diabetes. Combined aerobic/resistance exercise produces greater benefit in some QOL domains.