Involvement of the Macrophage Migration Inhibitory Factor (MIF) in Lipedema

Lipedema is a chronic disorder that mainly affects women. It is often misdiagnosed, and its etiology remains unknown. Recent research indicates an accumulation of macrophages and a shift in macrophage polarization in lipedema. One known protein superfamily that contributes to macrophage accumulation and polarization is the macrophage migration inhibitory factor (MIF) family. MIF-1 and MIF-2 are ubiquitously expressed and also regulate inflammatory processes in adipose tissue. In this study, the expression of MIF-1, MIF-2 and CD74-a common receptor for both cytokines-was analyzed in tissue samples of 11 lipedema and 11 BMI-matched, age-matched and anatomically matched control patients using qPCR and immunohistochemistry (IHC). The mRNA expression of MIF-1 (mean 1.256;SD 0.303;p = 0.0485) and CD74 (mean 1.514;SD 0.397;p = 0.0097) were significantly elevated in lipedema patients, while MIF-2 expression was unaffected (mean 1.004;SD 0.358;p = 0.9718). The IHC analysis corroborated the results for CD74 expression on a cellular level. In conclusion, our results provide first evidence for a potential involvement of the MIF family, presumably via the MIF-1-CD74 axis, in lipedema

Involvement of the Macrophage Migration Inhibitory Factor (MIF) in Lipedema

Lipedema is a chronic disorder that mainly affects women. It is often misdiagnosed, and its etiology remains unknown. Recent research indicates an accumulation of macrophages and a shift in macrophage polarization in lipedema. One known protein superfamily that contributes to macrophage accumulation and polarization is the macrophage migration inhibitory factor (MIF) family. MIF-1 and MIF-2 are ubiquitously expressed and also regulate inflammatory processes in adipose tissue. In this study, the expression of MIF-1, MIF-2 and CD74-a common receptor for both cytokines-was analyzed in tissue samples of 11 lipedema and 11 BMI-matched, age-matched and anatomically matched control patients using qPCR and immunohistochemistry (IHC). The mRNA expression of MIF-1 (mean 1.256; SD 0.303; p = 0.0485) and CD74 (mean 1.514; SD 0.397; p = 0.0097) were significantly elevated in lipedema patients, while MIF-2 expression was unaffected (mean 1.004; SD 0.358; p = 0.9718). The IHC analysis corroborated the results for CD74 expression on a cellular level. In conclusion, our results provide first evidence for a potential involvement of the MIF family, presumably via the MIF-1-CD74 axis, in lipedema

Sketching women in court: The visual construction of co-accused women in court drawings

This paper explores the visual construction and representation of co-accused women offenders in court drawings. It utilises three case studies of female co-defendants who appeared in the England and Wales court system between 2003 and 2013. In doing so this paper falls into three parts. The first part considers the emergence of the sub-discipline, visual criminology and examines what is known about the visual representation of female offenders. The second part presents the findings of an empirical investigation, which involved engaging in a critical, reflexive visual analysis of a selection of court drawings of three female co-offenders. The third part discusses the ways in which the court artists' interpretation, the conventions of court sketching, and motifs of female offenders as secondary actors, drew on existing myths and prejudices by representing the women as listening, remorseless ‘others’

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

ASO Visual Abstract: Vascularized Lymph Node Transfer Improved Outcomes of Elderly Secondary Upper Extremity Lymphedema

The vascularized lymph node transfer in elderly patients was a safe, reliable, and effective procedure with minimal complications. It has significantly decreased the frequency of cellulitis and improved the quality of life without using compression garments postoperatively

Vascularized Lymph Node Transfer Improved Outcomes of Elderly Patients with Secondary Upper Extremity Lymphedema

BACKGROUND: Secondary lymphedema is a debilitating morbidity. This study investigated the outcomes of vascularized lymph node transfer (VLNT) in elderly patients with secondary upper extremity lymphedema. METHODS: Between 2008 and 2018, elderly (≥65 years) patients with secondary upper extremity lymphedema who underwent VLNT were retrospectively reviewed. Cheng's Lymphedema Grading, Taiwan Lymphoscintigraphy Staging, and indocyanine green lymphography were used to select the procedures. Outcome measurements included complications, circumferential difference, episodes of cellulitis, and the Lymphedema-Specific Quality of Life questionnaire (LYMQoL). RESULTS: Eleven patients with a mean age of 70.2 ± 5.3 years (range 65-80 years) who underwent VLNT survived and no major complications were encountered. At a mean follow-up of 6.5 ± 3.6 years (range 2-13 years), the mean limb circumferential difference was significantly improved from 25.6 ± 11.5% to 8.3 ± 4.2% (p = 0.016), and the mean episode of cellulitis was statistically reduced from 2.4 ± 1.3 to 0.4 ± 0.9 times/year (p = 0.007). At a follow-up of 24 months, four domains of Function (from 30.6 ± 2.8 to 14.5 ± 2.5), Appearance (from 18.2 ± 1.9 to 8.5 ± 2.1), Symptoms (from 30.4 ± 5.9 to 10.9 ± 1.0) and Mood (from 29.2 ± 4.4 to 10.7 ± 1.0), as well as overall LYMQoL score (from 3.9 ± 1.1 to 7.4 ± 0.5), showed statistical improvement (all p < 0.05). CONCLUSIONS: VLNT for secondary upper extremity lymphedema in elderly patients significantly decreased the limb circumferential difference and frequency of cellulitis and improved quality of life without using compression garments postoperatively

A rare case of fournier’s gangrene

We report a rare case that highlights acute pancreatitis as the protagonist of Fournier\u27s Gangrene. This patient was treated with a radical debridement of his perineum at presentation and subsequently reconstructed with split thickness skin grafting. This is an unusual aetiology of necrotizing fasciitis with only one other case reported in the literature. This serves to emphasize to physicians that acute pancreatitis is a potential source when investigating and treating patients with Fournier\u27s Gangrene