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The Wound Healing Society guidelines for the treatment of arterial insufficiency ulcers were originally published in 2006, with the last update in 2014. These guidelines provided recommendations, along with their respective levels of evidence, on seven categories: diagnosis, surgery, infection control, wound bed preparation, dressings, adjuvant therapy and long-term maintenance. Over the last 9 years, additional literature regarding these aspects of arterial ulcer management has been published. An advisory panel comprised of academicians, clinicians and researchers was chosen to update the 2014 guidelines. Members included vascular surgeons, internists, plastic surgeons, anaesthesiologists, emergency medicine physicians and dermatologists, all with expertise in wound healing. The goal of this article is to evaluate relevant new findings upon which an updated version of the guidelines will be based., (© 2024 The Author(s). Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

The mechanisms connecting obesity with type 2 diabetes, insulin resistance, nonalcoholic fatty liver disease, and cardiovascular diseases remain incompletely understood. The function of MAPK phosphatase-2 (MKP-2), a type 1 dual-specific phosphatase (DUSP) in whole-body metabolism, and how this contributes to the development of diet-induced obesity, type 2 diabetes (T2D), and insulin resistance is largely unknown. We investigated the physiological contribution of MKP-2 in whole-body metabolism and whether MKP-2 is altered in obesity and human fatty liver disease using MKP-2 knockout mice models and human liver tissue derived from fatty liver disease patients. We demonstrate that, for the first time, MKP-2 expression was upregulated in liver tissue in humans with obesity and fatty liver disease and in insulin-responsive tissues in mice with obesity. MKP-2-deficient mice have enhanced p38 MAPK, JNK, and ERK activities in insulin-responsive tissues compared with wild-type mice. MKP-2 deficiency in mice protects against diet-induced obesity and hepatic steatosis and was accompanied by improved glucose homeostasis and insulin sensitivity. Mkp-2 -/- mice are resistant to diet-induced obesity owing to reduced food intake and associated lower respiratory exchange ratio. This was associated with enhanced circulating insulin-like growth factor-1 (IGF-1) and stromal cell-derived factor 1 (SDF-1) levels in Mkp-2 -/- mice. PTEN, a negative regulator of Akt, was downregulated in livers of Mkp-2 -/- mice, resulting in enhanced Akt activity consistent with increased insulin sensitivity. These studies identify a novel role for MKP-2 in the regulation of systemic metabolism and pathophysiology of obesity-induced insulin resistance and fatty liver disease.

Background: Mastectomy with immediate reconstruction is a high-risk cohort for postoperative nausea and vomiting (PONV). Known risk factors for PONV include female gender, prior PONV history, nonsmoker, age < 50, and postoperative opioid exposure. The objective of this observational, cohort analysis was to determine whether a standardized preoperative protocol with nonopioid and anti-nausea multimodal medications would reduce the odds of PONV., Methods: After IRB approval, retrospective data were collected for patients undergoing mastectomy with or without a nodal resection, and immediate subpectoral tissue expander or implant reconstruction. Patients were grouped based on treatment: those receiving the protocol - oral acetaminophen, pregabalin, celecoxib, and transdermal scopolamine (APCS); those receiving none (NONE), and those receiving partial protocol (OTHER). Logistic regression models were used to compare PONV among treatment groups, adjusting for patient and procedural variables., Main Findings: Among 305 cases, the mean age was 47 years (21-74), with 64% undergoing a bilateral procedure and 85% having had a concomitant nodal procedure. A total of 44.6% received APCS, 30.8% received OTHER, and 24.6% received NONE. The APCS group had the lowest rate of PONV (40%), followed by OTHER (47%), and NONE (59%). Adjusting for known preoperative variables, the odds of PONV were significantly lower in the APCS group versus the NONE group (OR=0.42, 95% CI: 0.20, 0.88 p = 0.016)., Conclusions: Premedication with a relatively inexpensive combination of oral non-opioids and an anti-nausea medication was associated with a significant reduction in PONV in a high-risk cohort. Use of a standardized protocol can lead to improved care while optimizing the patient experience., (Copyright © 2021 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

The liver plays a key role in whole-body, glucose and lipid homeostasis. Nutritional signals in response to fasting and refeeding regulate hepatic lipid synthesis. It is established that activation of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) in response to overnutrition regulates MAPK-dependent pathways that control lipid metabolism in the liver. However, the regulatory mechanisms and the impact of the actions of MKP-1 in hepatic response to fasting remains unclear. We investigated the effect of fasting on the expression of MKP-1 and the impact on hepatic response to feeding. In this study, we demonstrate that fasting stress induced upregulation of hepatic MKP-1 protein levels with a corresponding downregulation of p38 MAPK and JNK phosphorylation in mouse livers. We found that MKP-1-deficient livers are resistant to fasting-induced hepatic steatosis. Hepatic MKP-1 deficiency impaired fasting-induced changes in the levels of key transcription factors involved in the regulation of fatty acid and cholesterol metabolism including Srebf2 and Srebf1c . Mechanistically, MKP-1 negatively regulates Srebf2 expression by attenuating p38 MAPK pathway, suggesting its contribution to the metabolic effects of MKP-1 deficiency in the fasting liver. These findings support the hypothesis that upregulation of MKP-1 is a physiological relevant response and might be beneficial in hepatic lipid utilization during fasting in the liver. Collectively, these data unravel some of the complexity and tissue specific interaction of MKP-1 action in response to changes in nutritional cues, including fasting and excess nutrients.

The western diet and overuse of anti-inflammatory medication have caused a great deal of stress on the liver. Obesity and the associated inflammatory state in insulin-responsive tissues result in the release of pro-inflammatory cytokine that activates the stress-responsive MAPKs, p38 MAPK, and JNK. These MAPKs have figured prominently as critical effectors in physiological and pathophysiological hepatic inflammation. In contrast, evidence for a role for ERK1/2 in hepatic inflammation has been less well developed. In this review article, we describe recent insights into the physiology and pathophysiology of the role of stress-responsive MAPKs in hepatic inflammation during obesity and liver injury with a focus on macrophages, hepatocytes and hepatic stellate cells. In response to metabolic stress and liver injury, JNK activation in macrophages and hepatocytes promotes the secretion of inflammatory cytokines and macrophage and neutrophil infiltration. p38 MAPK plays an important role in contributing to the progression of hepatic inflammation in response to various hepatic cellular stresses, although the precise substrates mediating these effects in hepatocytes and hepatic stellate cells remain to be identified. Both JNK and p38 MAPK promotes profibrotic behavior in hepatic stellate cells., Competing Interests: Conflict of Interest No potential conflicts of interest relevant to this article were reported.

Standardized nonopioid preoperative protocol effects perioperative opioids. Combined use of acetaminophen, pregabalin, celecoxib, and transdermal scopolamine (APCS), in mastectomy with immediate subpectoral reconstruction procedures. Retrospective (2014-2017) cohort study (n = 305) examined treatment groups; APCS, no treatment (NONE), and partial combination APCS (OTHER), employing multivariable gamma regression models controlling preoperative and perioperative variables, examining postoperative opioid use (oral morphine equivalents, OME) and hospital stay (hours, LOS). APCS group had a 25% statistical reduction in OME total vs OTHER, a 12% statistical reduction in LOS vs OTHER, and 11% statistical reduction in LOS vs NONE. Standardized nonopioid preoperative protocol provides insight into perioperative opioid use., (© 2020 Wiley Periodicals, Inc.)

Patients belonging to some racial, ethnic, and socioeconomic groups are at risk of receiving suboptimal pain management. This study identifies health care provider attitudes, knowledge, and practices regarding the treatment of chronic pain in vulnerable patient populations and assesses whether a certified continuing medical education (CME) intervention can improve knowledge in this area. Survey responses revealed several knowledge gaps, including a lack of knowledge that the undertreatment of pain is more common in minority patients than others. Respondents identified language barriers, miscommunication, fear of medication diversion, and financial barriers as major obstacles to optimal pain management for this patient population. Participants who completed a CME-certified activity on pain management disparities demonstrated increased confidence in caring for disadvantaged patients, but only 1 of 3 knowledge items improved. Understanding clinician factors that underlie suboptimal pain management is necessary to develop effective strategies to overcome disparities and improve quality of care for patients with chronic pain., (© 2013 by the American College of Medical Quality.)

Timely interventional cancer pain therapies complement conventional pain management by reducing the need for high-dose opioid therapy and its associated toxicity. All patients with upper abdominal visceral pain should be considered for celiac plexus neurolysis soon after diagnosis. Intrathecal therapy should be considered in any patient with moderate-to-severe pain despite a reasonable therapeutic trial of opioid pharmacotherapy or in any patient intolerant of opioid therapy. Specific interventions for vertebral metastases and other sites of metastatic bone pain, including vertebroplasty, kyphoplasty, and image-guided tumor ablation, should be understood and considered. A collaborative model of care, including pain medicine specialists with expertise in interventional therapies, should be standard in all oncologic practices in order to optimize outcomes for patients with cancer throughout the course of their treatment.