Early diagnosis, a step towards reducing mortality in placenta accreta spectrum: a case series

The worldwide incidence of placenta accrete spectrum (PAS) is increasing day by day, mostly due to the increasing trends in caesarean section (CS) rates. PAS is accountable for high maternal morbidity and mortality as it is associated with extensive haemorrhage, which often requires hysterectomy, multiple blood and blood product transfusions, ureteric and bladder injuries and prolonged ICU stay. The aim of this case series is to highlight the importance of early diagnosis and high degree of suspicion of PAS for a planned management in decreasing maternal morbidity and mortality. Antenatal patients who were associated with PAS and managed in obstetrics and gynaecology department, Kalinga institute of medical sciences, Bhubaneswar during the time period of 2 years were critically reviewed and are being presented as case series. High degree of suspicion, pre operative radiological diagnosis, well preparedness and multidisciplinary approach help us in reducing the maternal mortality and morbidity significantly. Conservative management of PAS can preserve future fertility but should only be done in hospitals with 24 hour emergency care and enough expertise as it carries high chances of maternal complications

Immunosuppressive drugs in renal transplantation

A kidney transplant, sometimes known as a renal transplant, is the treatment of choice for kidney failure at end stage renal disease (ESRD). The renal transplant surgery is followed by a lifetime course of immunosuppressive agents, divided into initial induction phase and later maintenance phase. It is seen that the risk of acute rejection is maximum in the initial months after transplantation (induction phase) and then reduces later (maintenance phase). In induction phase there is use of high-intensity immunosuppression immediately after transplantation, when the risk of rejection is maximum and then the dose reduced for long- term therapy. The main challenge in the renal transplantation community is long- term transplant survival. Long-term graft loss is mainly due to acute and chronic graft rejection, and also due to complications of immunosuppressive therapy. Currently, there is triple therapy as conventional immunosuppressive protocol: a calcineurin inhibitor, an antimetabolite agent, and a corticosteroid. The main aim of development of new immunosuppressive agents is not only improvement of short- term outcomes but also to increase the long- term graft survival by less nephrotoxicity, and minimal side-effects

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Intranasal curcumin ameliorates lipopolysaccharide-induced acute lung injury in mice

Lipopolysaccharide (LPS) is one of the most powerful proinflammatory factor and can induce acute pulmonary inflammation even lung injury after inhalation or systemic administration. LPS induces sepsis and multiple organ damage. Curcumin (diferuloylmethane), a major component of turmeric, exhibits protection against LPS-induced acute lung injury (ALI). We aimed to investigate effects of intranasal curcumin on LPS-induced ALI in mice where curcumin (10 mg/kg, intranasal (i.n.) was given an hour before LPS exposure. After 24 h of intranasal LPS instillation, a marked increase in neutrophil recruitment and myeloperoxidase (MPO) activity was noted which were significantly ameliorated in curcumin treatment group. Oxidative stress markers like nitric oxide (NO), malondialdehyde (MDA) level and evans blue capillary leakage assay also revealed suppression after curcumin treatment; interestingly, levels of anti-oxidative enzymes such as superoxide dismutase (SOD) and catalase were upregulated. Inflammatory cytokine, tumour necrosis factor alpha (TNF-α) level was significantly attenuated by curcumin. Hence, intranasal curcumin could be a novel therapeutic strategy for LPS-induced ALI by directly targeting the lungs and enhancing anti-oxidant levels

Protective effects of intranasal curcumin on paraquot induced acute lung injury (ALI) in mice

Paraquot (PQ) is widely and commonly used as herbicide and has been reported to be hazardous as it causes lung injury. However, molecular mechanism underlying lung toxicity caused by PQ has not been elucidated. Curcumin, a known anti-inflammatory molecule derived from rhizomes of Curcuma longa has variety of pharmacological activities including free-radical scavenging properties but the protective effects of curcumin on PQ-induced acute lung injury (ALI) have not been studied. In this study, we aimed to study the effects of curcumin on ALI caused by PQ in male parke's strain mice which were challenged acutely by PQ (50 mg/kg, i.p.) with or without curcumin an hour before (5 mg/kg, i.n.) PQ intoxication. Lung specimens and the bronchoalveolar lavage fluid (BALF) were isolated for pathological and biochemical analysis after 48 h of PQ exposure. Curcumin administration has significantly enhanced superoxide dismutase (SOD) and catalase activities. Lung wet/dry weight ratio, malondialdehyde (MDA) and lactate dehydrogenase (LDH) content, total cell number and myeloperoxidase (MPO) levels in BALF as well as neutrophil infiltration were attenuated by curcumin. Pathological studies also revealed that intranasal curcumin alleviate PQ-induced pulmonary damage and pro-inflammatory cytokine levels like tumor necrosis factor-α (TNF-α) and nitric oxide (NO). These results suggest that intranasal curcumin may directly target lungs and curcumin inhalers may prove to be effective in PQ-induced ALI treatment in near future