DPP-4 inhibitor sitagliptin treatment results in altered myocardial metabolic proteome and oxidative phosphorylation in a swine model of chronic myocardial ischemia.

Small animal models have shown improved cardiac function with DPP-4 inhibition, but many human studies have shown worse outcomes or no benefit. We seek to bridge the gap by studying the DPP-4 inhibitor sitagliptin in a swine model of chronic myocardial ischemia using proteomic analysis. Thirteen Yorkshire swine underwent the placement of an ameroid constrictor on the left coronary circumflex artery to model chronic myocardial ischemia. Two weeks post-op, swine received either sitagliptin 100 mg daily (SIT, n = 5) or no drug (CON, n = 8). After 5 weeks of treatment, swine underwent functional measurements and tissue harvest. In the SIT group compared to CON, there was a trend towards decreased cardiac index (p = 0.06). The non-ischemic and ischemic myocardium had 396 and 166 significantly decreased proteins, respectively, in the SIT group compared to CON (all p < 0.01). This included proteins involved in fatty acid oxidation (FAO), myocardial contraction, and oxidative phosphorylation (OXPHOS). Sitagliptin treatment resulted in a trend towards decreased cardiac index and decreased expression of proteins involved in OXPHOS, FAO, and myocardial contraction in both ischemic and non-ischemic swine myocardium. These metabolic and functional changes may provide some mechanistic evidence for outcomes seen in clinical studies.

Association Between Marijuana Use and Clinical Outcomes After Coronary Artery Bypass Grafting.

INTRODUCTION: Though marijuana use has been linked to an increase in heart failure admissions, no prior study has explored the association between its use and outcomes after coronary artery bypass grafting (CABG). This study examines the relationship between marijuana use and postoperative outcomes in CABG patients. METHODS: We utilized data from the National Inpatient Sample database from 2008 to 2018 for CABG patients ≥18 y old. Patients were divided into two groups based on marijuana use (abuse/dependency versus nonuse). Primary outcomes include in-hospital mortality, favorable discharge, and length of stay (LOS). Secondary outcomes include acute kidney injury (AKI), acute myocardial infarction (AMI), and transient ischemic attack (TIA)/stroke. A multivariable model, adjusted for confounding variables, was utilized for each outcome. RESULTS: A total of 343,796 patients met inclusion criteria for the study, 590 of which were marijuana users. In both marijuana user and nonuser groups, most patients were male and White with an average age of 56.0 and 66.3 y, respectively. There was a nonsignificant decreased odds of in-hospital mortality among marijuana users (odds ratio [OR] = 0.41, [0.141-1.124]). Marijuana users exhibited significantly decreased odds of home discharge (OR = 1.50, [1.24-1.81]), and increased odds of longer LOS (mean 10.4 d versus 9.8 d; OR = 1.14, [1.09-1.20]), AKI (OR = 1.40, [1.11-1.78]), AMI (OR = 1.56, [1.32-1.84]), and TIA/stroke (OR = 1.64, [1.21-2.22]). CONCLUSIONS: Marijuana use and dependency are associated with increased nonhome discharge, AKI, AMI, TIA/stroke, and longer LOS. Further studies are needed to delineate the pathophysiologic derangements that contribute to these unfavorable post-CABG outcomes.

Orthopedic Surgery Residencies: The Leap to Social Media.

Social media has been previously shown to influence applicants' perception of plastic surgery residencies and increase their likelihood to apply, interview, and rank the program. We wanted to analyze this hypothesized trend in the context of orthopedic surgery residency while also characterizing the content of orthopedic surgery residency program accounts. A current list of US orthopedic residency programs was acquired from the American Orthopaedic Association and cross-referenced with the Accreditation Council for Graduate Medical Education webpage of all orthopedic surgery residencies. Forty-five of 185 (24%) residencies had residency-specific Instagram accounts. We analyzed the number of followers, the number of posts, and the date of the first post for each account. We characterized content by categories including science education, recruitment or hospital promotion, resident highlight, news coverage, events, and community building posts. We analyzed the "social currency" of each post and program, tracking the number of likes, comments, and followers. Twenty-seven of 45 (60%) active residency Instagram pages were created in 2020, with 13 of 45 (29%) pages created in June 2020 alone. Residency programs are increasingly turning to Instagram to showcase the residents at their programs, their lifestyles, and program strengths. Sixty percent of all orthopedic residency Instagram accounts were created in 2020 alone, likely precipitated by travel concerns from COVID-19 forcing programs to conduct online interviews and cancel away rotations this application cycle. Going forward, residency programs will continue using Instagram to recruit potential residents, leaving programs without social media accounts at a relative disadvantage in terms of visibility and their ability to recruit qualified applicants. [Orthopedics. 2023;46(5):e281-e286.].

Perioperative management of acetabular and pelvic fractures: evidence-based recommendations.

PURPOSE: The American Academy of Orthopaedic Surgeons does not currently provide clinical practice guidelines for management of PAF. Accordingly, this article aims to review and consolidate the relevant historical and recent literature in important topics pertaining to perioperative management of PAF. METHODS: A thorough literature review using PubMed, Cochrane and Embase databases was performed to assess preoperative, intraoperative and postoperative management of PAF fracture. Topics reviewed included: time from injury to definitive fixation, the role of inferior vena cava filters (IVCF), tranexamic acid (TXA) use, intraopoperative cell salvage, incisional negative pressure wound therapy (NPWT), intraoperative antibiotic powder use, heterotopic ossification prophylaxis, and pre- and postoperative venous thromboembolism (VTE) prophylaxis. RESULTS: A total of 126 articles pertaining to the preoperative, intraoperative and postoperative management of PAF were reviewed. Articles reviewed by topic include 13 articles pertaining to time to fixation, 23 on IVCF use, 14 on VTE prophylaxis, 20 on TXA use, 10 on cell salvage, 10 on iNPWT 14 on intraoperative antibiotic powder and 20 on HO prophylaxis. An additional eight articles were reviewed to describe background information. Five articles provided information for two or more treatment modalities and were therefore included in multiple categories when tabulating the number of articles reviewed per topic. CONCLUSION: The literature supports the use of radiation therapy for HO prophylaxis, early (< 5 days from injury) surgical intervention and the routine use of intraoperative TXA. The literature does not support the routine use of iNPWT or IVCF. There is inadequate information to make a recommendation regarding the use of cell salvage and wound infiltration with antibiotic powder. While the routine use of chemical VTE prophylaxis is recommended, there is insufficient evidence to recommend the optimal agent and duration of therapy.

Poorly controlled hypertension is associated with increased coronary myogenic tone in patients undergoing cardiac surgery with cardiopulmonary bypass.

OBJECTIVE: Cardioplegia and cardiopulmonary bypass dysregulate coronary vasomotor tone, which can be further affected by common comorbidities in patients undergoing cardiac surgery. This study investigates differences in coronary myogenic tone and vasomotor responses to phenylephrine before and after cardioplegia and cardiopulmonary bypass based on hypertension history. METHODS: Coronary arterioles before and after cardioplegia and cardiopulmonary bypass were dissected from atrial tissue samples in patients with no hypertension, well-controlled hypertension, or uncontrolled hypertension, as determined by documented history of hypertension, antihypertensive agent use, and clinical blood pressure measurements averaged over 1 year. Myogenic tone in response to stepwise increases in intraluminal pressure was studied between pressure steps. Microvascular reactivity in response to phenylephrine was assessed via vessel myography. Protein expression was measured with immunoblotting. RESULTS: Coronary myogenic tone was significantly increased in the uncontrolled hypertension group compared with the no hypertension and well-controlled hypertension groups before cardioplegia and cardiopulmonary bypass at higher intraluminal pressures, and after cardioplegia and cardiopulmonary bypass across all intraluminal pressures (P < .05). Contractile responses to phenylephrine were significantly enhanced in patients in the uncontrolled hypertension group compared with the well-controlled hypertension group before cardioplegia and cardiopulmonary bypass, and in the uncontrolled hypertension group compared with the no hypertension and well-controlled hyertension groups after cardioplegia and cardiopulmonary bypass (P < .05). There were no differences in myogenic tone or phenylephrine-induced reactivity between the no hypertension and well-controlled hypertension groups (P > .05). There was increased expression of phosphorylated protein kinase C alpha in the uncontrolled hypertension group after cardiopulmonary bypass compared with before cardiopulmonary bypass and increased phosphorylated extracellular signal-regulated kinase 1/2 in the uncontrolled hypertension compared with the no hypertension group after cardiopulmonary bypass (P < .05). CONCLUSIONS: Uncontrolled hypertension is associated with increased coronary myogenic tone and vasoconstrictive response to phenylephrine that persists after cardioplegia and cardiopulmonary bypass.

Effects of canagliflozin on myocardial microvascular density, oxidative stress, and proteomic profile☆.

Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are cardioprotective, and canagliflozin (CANA), an SGLT2i, has been shown to improve perfusion, AMPK signaling, and oxidative stress in chronically ischemic myocardium. The aim of this study is to determine the effects of CANA in nonischemic myocardium on coronary collateralization, oxidative stress, and other molecular pathways determined by proteomic profiling. Methods: Yorkshire swine underwent placement of an ameroid constrictor to the left circumflex artery. Two weeks later, pigs received no drug (CON, n = 8) or 300 mg CANA daily (n = 8). Treatment continued for five weeks, followed by tissue harvest of nonischemic myocardium. Results: CANA was associated with decreased capillary density (p = 0.05) compared to CON, without changes in arteriolar density. Reduced capillary density did not correlate with reduced perfusion. Oxidative stress was reduced with CANA (22 % decrease). In the CANA group, there was a trend towards increased p-eNOS and eNOS, without a change in p-eNOS/eNOS ratio, p-Akt, Akt, and p-Akt/Akt ratio. There was no change in p-ERK1/2, but a decrease in total ERK1/2 and increase in p-ERK1/2/ERK1/2 ratio. There were no changes in expression of p-AMPK, AMPK, with a trend towards increased ratio of p-AMPK/AMPK. Proteomics analysis identified 2819 common proteins, of which 120 were upregulated and 425 were downregulated with CANA. Pathway analysis demonstrated wide regulation of metabolic proteins. Conclusions: The effects of CANA on myocardial perfusion and AMPK signaling in chronically ischemic myocardium are not found in nonischemic territory, despite attenuation of oxidative stress. Metabolic proteins are widely regulated in nonischemic myocardium with CANA.

Innovation in Resident Selection: Life Without Step 1.

INTRODUCTION: The announcement of Step 1 shifting to a Pass/Fail metric has prompted resident selection committees (RSCs) to pursue objective methods of evaluating prospective residents. Regardless of the program's specialty or affiliated hospital/school, RSCs universally aim to recognize and choose applicants who are an "optimal fit" to their programs.1 An optimal fit can be defined as a candidate who thrives in the clinical and academic setting, both contributing to and benefiting from their respective training environments. OBJECTIVE: The objective of this scoping review is to evaluate alternative, innovative methods by which RSCs can evaluate applicants and predict success during residency. Objective methods include: Step 2 scores, Traditionally Used Metrics (core clerkship scores), interview performance, musical talent, sports involvement, AOA membership, research publications, unprofessional behavior, Dean's letters, Rank list, judgement testing, and specialty-specific shelf exams.13-15. METHODS: A scoping review was performed in compliance with the guidelines indicated by the PRISMA Protocol for scoping review.18 9308 results were identified in the original PubMed search for articles with the key words "Resident Success". Abstract screening and application of inclusion and exclusion criteria yielded 97 articles that were critically appraised via review of full manuscript. RESULTS: Of the articles that focused on personality traits, situational judgement testing, and specialty specific pre-assessment, all of them demonstrated some level of predictability for resident success. Standardized Letter of Recommendations, Traditionally Used Metrics, and STEP 2 did not show a unanimous consensus in demonstrating predictability of a resident's success, this is because some articles suggested predictability and some articles disputed predictability. CONCLUSION: The authors found personality traits, situational judgement testing, and specialty specific assessments to be predictive in selecting successful residents. Further research should aim to analyze exactly how RSCs utilize these assessment tools to aid in screening their large and competitive applicant pools to find residents that will be successful in their program.

Technique, Efficiency and Safety of Different Nerve Blocks for Analgesia in Laser Ablation and Sclerotherapy for Lower Limb Superficial Venous Insufficiency - A Multicentre Experience.

INTRODUCTION: Laser ablation and sclerotherapy, as minimally invasive alternatives to surgery for varicose veins, have good efficacy, safety and cosmetic result. Some form of anaesthesia is generally used for pain control. AIM: To describe the technique and evaluate the efficacy and safety of femoral, saphenous and sciatic nerve blocks in isolation or in combination for analgesia during laser ablation and sclerotherapy for lower limb varicose veins. MATERIALS AND METHODS: In this prospective observational study, over a period of 33 months, in 856 limbs of 681 patients with varicose veins, ultrasound guided femoral, saphenous and sciatic nerve blocks for analgesia were performed in 769, 808 and 52 instances respectively; following which, endovenous laser ablation, sclerotherapy or combination of both were carried out using standard practice. After completion of the procedure, Visual Analogue Pain Scale (VAS) was used for pain assessment, and muscle weakness was assessed clinically. RESULTS: Nerve blocks could be successfully performed in all patients. Observed pain scores were 0 or 1 in 591 (69%), 2 or 3 in 214 (25%) and 4 in 51 (9%) legs with no score more than 4. Higher grades of pain were noted in femoral blocks during early stages of our learning curve. Mild to moderate muscle weakness was observed in 163 (2%) and 7 (13%) patients who underwent femoral and sciatic block respectively, which persisted for an average of two and a half hours and none beyond four and a half hours; saphenous nerve being a pure sensory nerve, did not cause motor weakness. CONCLUSION: For analgesia during laser ablation and/or sclerotherapy of varicose veins, ultrasound guided nerve blocks can be easily and quickly performed. They provide excellent pain relief and comfort to the patient and to the operator; and they do not cause any additional complication.

A rare case of male primary breast lymphoma.

Primary lymphoma of the breast is a rare occurrence because of the paucity of lymphoid tissue in the breast and is an even rarer entity in the male breast. Imaging, along with tissue diagnosis goes a long way in diagnosing breast lymphoma which has a significantly different management scheme than other breast neoplasms with respect to radio-chemotherapy rather than surgical resection. We present a case of primary male breast lymphoma which was evaluated with magnetic resonance imaging as well as other conventional imaging modalities and was treated by chemotherapy with a 7-month follow-up.