Schistosomal appendicitis: Case series and systematic literature review

Background Globally, schistosomiasis affects at least 240 million people each year with a high proportion of cases in sub-Saharan Africa. The infection presents a wide range of symptoms mainly at the gastrointestinal and urogenital level. Cases of schistosomiasis-related appendicitis are seldom reported. The aim of the present study is to identify the prevalence of schistosomiasis-related appendicitis in Beira, Mozambique and compare to global prevalence. Methods We retrospectively reviewed all cases of appendicitis recorded from January 2017 to March 2020 at a single pathology department located in Beira in order to assess the prevalence of schistosomiasis. Moreover, we performed a systematic review on the prevalence of schistosomiasis-related appendicitis in all countries. Findings A total of 145 appendicitis cases in Beira showed a 13.1% prevalence of schistosomal-related appendicitis. The mean age of patients was 29.1 years, and 14 (73.7%) were male. The systematic review identified 20 studies with 34,790 inpatientsAUwith: schistosomiasis-related appendicitis with a global prevalence of 1.31% (95% confidence interval (CI): 0.72 to PerPLOSstyle; sufferingfrom2.06); a high heterogeneity (I2 = 96.0%) was observed. Studies carried out in Africa reported a significantly higher prevalence of schistosomiasis-related appendicitis (2.75%; 95% CI: 1.28 to 4.68) than those in Middle East (0.49%; 95% CI: 0.18 to 0.95) (p for interaction < 0.0001). Conclusions Schistosomiasis infection should be considered as possible cause of appendicitis not only in endemic areas but also in developed countries. Considering that prevention is the best way to control the infection, more efforts should be put in place in order to increase the prevention coverage and avoid the cascading implications for health. This is even more so important in this Coronavirus Disease 2019AU(COVID-19): PleasenotethatCOVIDera where the majority19hasbeendefinedasCoof attention and funds are used to fight the pandemic

Empagliflozin Use and Fournier’s Gangrene: Case Report and Systematic Literature Review

Background: Fournier’s gangrene (FG) is a rare necrotising soft tissue infection localised in the genital areas with possible dramatic outcomes. Recently, sodium glucose co-transporter-2 (SGLT2) inhibitors were identified as a risk factor. Methods: We present a case report of a 57-year-old female patient with type 2 diabetes mellitus (T2DM) in treatment with empagliflozin which led to the development of FG. Moreover, we performed a systematic review assessing the association between empagliflozin use and FG. Results: The female patient with 15-years treated diabetes presented a massive FG after 6 months from starting empagliflozin. Over the period of two months, she was successfully treated in a low-income setting. The systematic review included two studies with a total of 9915 participants. Although no participant had FG, there was an increased rate of urinary and genital infection in patients treated with empagliflozin compared to those treated with other antidiabetics or placebo. Conclusions: FG should be considered as a possible complication in patients using SGLT2. Patients should be educated to report early signs of genital infection and healthy behaviours as well as a balanced diet should be promoted to aid in the prevention of FG

A Multicenter Phase 2 Randomized Controlled Study on the Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients with COVID-19 Pneumonia

Introduction Acute lung injury and acute respiratory distress syndrome are common complications in patients with coronavirus disease 2019 (COVID-19). Poor outcomes in patients with COVID-19 are associated with cytokine release syndrome. Binding of interleukin-8 (CXCL8/IL-8) to its chemokine receptors, CXCR1/2, may mediate this inflammatory process. The aim of this clinical trial was to determine if CXCR1/2 blockade with reparixin can improve clinical outcomes in hospitalized patients with severe COVID-19 pneumonia. The dose and safety of reparixin have been investigated in clinical trials of patients with metastatic breast cancer. Methods This was a phase 2, open-label, multicenter, randomized study in hospitalized adult patients with severe COVID-19 pneumonia from May 5, 2020 until November 27, 2020. Patients were randomized 2:1 to receive 1200 mg reparixin orally three times daily or standard of care (SOC) for up to 21 days. The primary endpoint was defined as a composite of clinical events: use of supplemental oxygen, need for mechanical ventilation, intensive care unit admission, and/or use of rescue medication. Results Fifty-five patients were enrolled between reparixin (n = 36) and SOC (n = 19). The rate of clinical events was statistically significantly lower in the reparixin group compared with the SOC group (16.7% [95% CI 6.4-32.8%] vs. 42.1% [95% CI 20.3-66.5%], P = 0.02). The sensitivity analysis based on the Cox regression model provided an adjusted hazard ratio of 0.33 with statistical significance lower than 0.05 (95% CI 0.11-0.99; P = 0.047). Reparixin treatment appeared to be well tolerated. Conclusion In patients with severe COVID-19, reparixin led to an improvement in clinical outcomes when compared with the SOC. A larger phase 3 clinical study is needed to confirm these results

Mitochondria dysfunction is associated with long-term cognitive impairment in an animal sepsis mode

Background: Several different mechanisms have been proposed to explain long-term cognitive impairment in sepsis survivors. The role of persisting mitochondrial dysfunction is not known. We thus sought to determine whether stimulation of mitochondrial dynamics improves mitochondrial function and long-term cognitive impairment in an experimental model of sepsis. Methods: Sepsis was induced in adult Wistar rats by cecal ligation and perforation (CLP). Animals received intracerebroventricular injections of either rosiglitazone (biogenesis activator), rilmenidine, rapamycin (autophagy activators), or n-saline (sham control) once a day on days 7–9 after the septic insult. Cognitive impairment was assessed by inhibitory avoidance and object recognition tests. Animals were killed 24 h, 3 and 10 days after sepsis with the hippocampus and prefrontal cortex removed to determine mitochondrial function. Results: Sepsis was associated with both acute (24 h) and late (10 days) brain mitochondrial dysfunction. Markers of mitochondrial biogenesis, autophagy and mitophagy were not up-regulated during these time points. Activation of biogenesis (rosiglitazone) or autophagy (rapamycin and rilmenidine) improved brain ATP levels and ex vivo oxygen consumption and the long-term cognitive impairment observed in sepsis survivors. Conclusion: Long-term impairment of brain function is temporally related to mitochondrial dysfunction. Activators of autophagy and mitochondrial biogenesis could rescue animals from cognitive impairment

Complex nanoemulsion for vitamin delivery:Droplet organization and interaction with skin membranes

Lipid nanoemulsions are promising nanomaterials for drug delivery applications in food, pharmaceutical and cosmetic industries. Despite the noteworthy commercial interest, little is known about their supramolecular organization, especially about how such multicomponent formulations interact with cell membranes. In the present work, coarse-grained molecular dynamics simulations have been employed to study the self-assembly of a 15-component lipid nanoemulsion droplet containing vitamins A and E for skin delivery. Our results display aspects of the unique "onion-like" agglomeration between the chemical constituents in the different layers of the lipid nanodroplet. Vitamin E molecules are more concentrated in the center of the droplet together with other hydrophobic constituents such as the triglycerides with long tails. On the other hand, vitamin A occupies an intermediate layer between the core and the co-emulsifier surface of the nanodroplet, together with lecithin phospholipids. Coarse-grained molecular dynamics simulations were also performed to provide insight into the first steps involved in absorption and penetration of the nanodroplet through skin membrane models, representing an intracellular (hair follicle infundibulum) and intercellular pathway (stratum corneum) through the skin. Our data provide a first view on the complex organization of commercial nanoemulsion and its interaction with skin membranes. We expect our results to open the way towards the rational design of such nanomaterials

Effects of age, line and diet on the occurrence of white striping lesions in broiler breast muscle.

Abstract: The White Striping (WS) is one of the most prevalent pectoral myopathies in chickens affecting meat quality. Its etiology, as well as the influence of diet, age and line, remains unclear. Therefore, effects of broiler line, nutrition and age were investigated to better understand and identify possible causative mechanisms triggering the onset and the progression of WS myopathy in the breast of broiler chickens. The most relevant macroscopic lesion observed was white striations on the surface of the breasts. For the lesion identified macroscopically, Ross had an odds ratio of 8.43 in relation to TT line, while for the microscopic lesion the odds ratio was 22.52. The high-performance diet had an odds ratio of 1.76 in relation to the regular diet for the macroscopic lesions only. Therefore, we have shown that the presence of WS increases with age even in broiler lines that have slower growth rate than commercial lines

The macrophage tetraspan MS4A4A enhances dectin-1-dependent NK cell-mediated resistance to metastasis

Fondazione Cariplo (grant no. 2015–0564 to A.M.)Cluster Alisei (grant no. MEDINTECH CTN01_00177_962865 to A.M.)European Research Council (grant no. 669415-PHII to A.M.)Italian Association for Cancer Research (AIRC IG-2016 grant no. 19014 to A.M.; AIRC 5 × 1000 grant no. 21147 to A.M.; AIRC IG-2016 grant no. 19213 to M.L.)Medical Research Council (Pathobiology of Early Arthritis Cohort grant no. 36661 to C.P.)Arthritis Research UK Experimental Treatment Centre (grant no. 20022 to C.P.

Pressure-support ventilation or T-piece spontaneous breathing trials for patients with chronic obstructive pulmonary disease : a randomized controlled trial

Background Little is known about the best strategy for weaning patients with chronic obstructive pulmonary disease (COPD) from mechanical ventilation. Spontaneous breathing trials (SBT) using a T-piece or pressure-support ventilation (PSV) have a central role in this process. Our aim was to compare T-piece and PSV SBTs according to the duration of mechanical ventilation (MV) in patients with COPD. Methods Patients with COPD who had at least 48 hours of invasive MV support were randomized to 30 minutes of T-piece or PSV at 10 cm H2O after being considered able to undergo a SBT. All patients were preemptively connected to non-invasive ventilation after extubation. Tracheostomized patients were excluded. The primary outcome was total invasive MV duration. Time to liberation from MV was assessed as secondary outcome. Results Between 2012 and 2016, 190 patients were randomized to T-piece (99) or PSV (91) groups. Extubation at first SBT was achieved in 78% of patients. The mean total MV duration was 10.82 ± 9.1 days for the T-piece group and 7.31 ± 4.9 days for the PSV group (p < 0.001); however, the pre-SBT duration also differed (7.35 ± 3.9 and 5.84 ± 3.3, respectively; p = 0.002). The time to liberation was 8.36 ± 11.04 days for the T-piece group and 4.06 ± 4.94 for the PSV group (univariate mean ratio = 2.06 [1.29±3.27], p = 0.003) for the subgroup of patients with difficult or prolonged weaning. The study group was independently associated with the time to liberation in this subgroup.Conclusions The SBT technique did not influence MV duration for patients with COPD. For the difficult/ prolonged weaning subgroup, the T-piece may be associated with a longer time to liberation, although this should be clarified by further studies