The Fournier's gangrene severity index remains an objective and simple method to quantify the extent of metabolic aberration at presentation in patients with Fournier's gangrene. A Fournier's gangrene severity index threshold value of 9 is sensitive and specific for predicting mortality in this patient population.

Key Points Question Does COVID-19 convalescent plasma (CCP), compared with placebo, improve the clinical status of hospitalized patients with COVID-19 requiring noninvasive supplemental oxygen? Findings In this randomized clinical trial including 941 patients, based on the World Health Organization 11-point Ordinal Scale for Clinical Improvement, CCP did not benefit 468 participants randomized to CCP compared with 473 randomized to placebo from April 2020 to March 2021. However, in exploratory analyses, CCP appeared to benefit those enrolled from April to June 2020, the period when most participants received high-titer CCP and were not receiving remdesivir and corticosteroids at randomization. Meaning In this trial, CCP did not meet prespecified outcomes for efficacy, but high-titer CCP may have benefited hospitalized patients with COVID-19 early in the pandemic when other treatments were not in use, suggesting a heterogenous treatment effect over time.

Background:The Akt/mammalian target of rapamycin (mTOR) signalling pathway serves as a critical regulator of cellular growth, proliferation and survival. Akt aberrant activation has been implicated in carcinogenesis and anticancer therapy resistance. Piperlongumine (PL), a natural alkaloid present in the fruit of the Long pepper, is known to exhibit notable anticancer effects. Here we investigate the impact of PL on Akt/mTOR signalling.Methods:We examined Akt/mTOR signalling in cancer cells of various origins including prostate, kidney and breast after PL treatment. Furthermore, cell viability after concomitant treatment with PL and the autophagy inhibitor, Chloroquine (CQ) was assessed. We then examined the efficacy of in vivo combination treatment using a mouse xenograft tumour model.Results:We demonstrate for the first time that PL effectively inhibits phosphorylation of Akt target proteins in all tested cells. Furthermore, the downregulation of Akt downstream signalling resulted in decrease of mTORC1 activity and autophagy stimulation. Using the autophagy inhibitor, CQ, the level of PL-induced cellular death was significantly increased. Moreover, concomitant treatment with PL and CQ demonstrated notable antitumour effect in a xenograft mouse model.Conclusions:Our data provide novel therapeutic opportunities to mediate cancer cellular death using PL. As such, PL may afford a novel paradigm for both prevention and treatment of malignancy.

Purpose This study investigated the cytokine profile in bladder tissue and urine of painful bladder syndrome/interstitial cystitis (PBS/IC) patients. Methods Multiplex analysis of 23 cytokines was performed with a multiple antigen bead assay (Luminex 100 IS) on cold cup bladder biopsy and urine specimens collected during cystoscopy with hydrodistention (HD) under general anesthesia from 10 PBS/IC patients (ICS definition). Collected tissue specimens and urine from pre-HD and post-HD (mean 27 days) were compared to banked urine and tissue specimens (n = 10) collected from control subjects without PBS/IC symptoms. Results Univariate comparison of bladder tissue levels found significant elevation of IL-16, IL-18, CTACK, ICAM-1, MCP-3, SCGFβ, TRAIL, and VCAM-1 in PBS/IC relative to controls. Multivariate analysis revealed VCAM-1 and ICAM-1 were responsible for the discrimination of both tissue and urine of PBS/IC from controls. Urine levels of MCP-3 and TRAIL were significantly reduced a month after HD in concert with improvement in standardized measures of clinical symptoms (pain, urgency, and frequency (PUF) overall score [mean 25.8 ± 5.5 vs. 20.3 ± 7, p = 0.04] and symptom score [mean 18.2 ± 3.2 vs. 12.2 ± 5.9; p = 0.009]). Post-HD urine levels of MCSF(r = 0.88; p = 0.003), MCP-3 (r = 0.81; p = 0.01), SDF1α (r = 0.82; p = 0.01), and IL-18 (r = 0.64; p = 0.08) positively correlated with improved symptom scores. Conclusions These results indicate significant elevation of cytokines in PBS/IC bladder tissue relative to controls. Significant reduction in post-HD urine levels of MCP-3 and TRAIL relative to pre-HD in PBS/IC was associated with clinical improvement (as measured by PBS/IC symptom scores) to qualify them as biomarker candidates.