Accelerated diabetic wound healing by topical application of combination oral antidiabetic agents-loaded nanofibrous scaffolds: An in vitro and in vivo evaluation study

The combination of oral antidiabetic drugs, pioglitazone, metformin, and glibenclamide, which also exhibit the strongest anti-inflammatory action among oral antidiabetic drugs, were loaded into chitosan/gelatin/polycaprolactone (PCL) by electrospinning and polyvinyl pyrrolidone (PVP)/PCL composite nanofibrous scaffolds by pressurized gyration to compare the diabetic wound healing effect. The combination therapies significantly accelerated diabetic wound healing in type-1 diabetic rats and organized densely packed collagen fibers in the dermis, it also showed better regeneration of the dermis and epidermis than single drug-loaded scaffolds with less inflammatory cell infiltration and edema. The formation of the hair follicles started in 14 days only in the combination therapy and lower proinflammatory cytokine levels were observed compared to single drug-loaded treatment groups. The combination therapy increased the wettability and hydrophilicity of scaffolds, demonstrated sustained drug release over 14 days, has high tensile strength and suitable cytocompatibility on L929 (mouse fibroblast) cell and created a suitable area for the proliferation of fibroblast cells. Consequently, the application of metformin and pioglitazone-loaded chitosan/gelatin/PCL nanofibrous scaffolds to a diabetic wound area offer high bioavailability, fewer systemic side effects, and reduced frequency of dosage and amount of drug

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Administration of local anesthetic through the epidural needle before catheter insertion improves the quality of anesthesia and reduces catheter-related complications

Epidural catheter placement offers flexibility in block management. However, during epidural catheter insertion, complications such as paresthesia and venous and subarachnoid cannulation may occur, and suboptimal catheter placement can affect the quality of anesthesia. We performed this prospective, randomized, double-blind study to assess the effect of a single-injection dose of local anesthetic (20 mL of 2% lidocaine) through the epidural needle as a priming solution into the epidural space before catheter insertion. We randomized 240 patients into 2 equal groups and measured the quality of anesthesia and the incidence of complications. In the needle group (n = 100), catheters were inserted after injection of a full dose of local anesthetic through the needle. In the catheter group (n = 98), the catheters were inserted immediately after identification of the epidural space. Local anesthetic was then injected via the catheter. We noted the occurrence of paresthesia, inability to advance the catheter, or IV or subarachnoid catheter placement. Sensory and motor block were assessed 20 min after the injection of local anesthetic. Surgery was initiated when adequate sensory loss was confirmed. In the catheter group, the incidence of paresthesia during catheter placement was 31.6% compared with 11% in the needle group (P = 0,00038). IV catheterization occurred in 8.2% versus 2% of patients in the catheter and needle groups, respectively (P = 0.048). More patients in the needle group had excellent surgical conditions than the catheter group (89.6% versus 72.9; P < 0.003). We conclude that giving a single-injection dose via the epidural needle before catheter placement improves the quality of epidural anesthesia and reduces catheter-related complications

Effects of sevoflurane and desflurane in CA1 after incomplete cerebral ischemia in rats

Objectives: We compared the postischemic cerebral protective effects of sevoflurane and desflurane in rats with incomplete cerebral ischemia

The Effect of Hyperbaric Oxygen Therapy on Rhabdomyolysis-Induced Myoglobinuric Acute Renal Failure in Rats

Myoglobinuric acute renal failure (MARF) may develop after severe muscle injury. Heme oxygenase-1 (HO-1), a stress-response protein, has been implicated as a protective agent against MARF. We hypothesized that hyperbaric oxygen therapy (HBOT) may alleviate MARF by inducing renal HO-1 expression. Wistar-Albino rats were randomly assigned into three groups: Control (n=4), MARF (n=8), MARF+HBO (n=8). MARF was induced by intramuscular glycerol (50%, 8mL/kg) injection. Saline (8mL/kg) was injected into the hind limb of the animals in the control group. Animals in the MARF+HBO group received two sessions of HBO therapy (90min at 2.5atm) 2 and 18h after glycerol injection. Serum and tissue samples were taken at 24h. Serum urea and creatinine levels increased in the MARF and MARF+HBO groups confirming the development of MARF. But, serum urea and creatinine levels were similar in MARF and MARF+HBO groups. Oxidative stress parameters were similar among all groups. Histological renal injury score was similar in MARF and MARF+HBO groups. HO-1 level, determined by immunohistochemistry, was significantly higher in MARF and MARF+HBO groups, compared to the control group. Although HO-1 level in MARF+HBO group was higher than MARF group, it was not statistically significant. We found that HBOT did not reduce renal injury in experimental MARF model. HBOT is used to reduce the muscle damage after crush injury, which may be accompanied by MARF. Therefore, more studies are needed to understand the effects of HBO treatment on renal functions after MARF.WoSScopu

Evaluation of children with nutritional rickets

Aim: To evaluate the clinical findings, risk factors, therapy and outcome in 946 children with nutritional rickets