Clinical and serological studies of tuberculosis patients in Argentina receiving immunotherapy with Mycobacterium vaccae (SRL 172)

AbstractTwo small, placebo-controlled studies of immunotherapy with heat killed Mycobacterium vaccae added to routine chemotherapy for pulmonary tuberculosis, together involving 40 HIV seronegative patients, were carried out in Argentina. The immunotherapy was associated with reduced sputum smear positivity of AFB at 1 month and a greater reduction in ESR at 2 months. In the first study radiological improvement was better (P < 0·05) among immunotherapy recipients. In the second study, weight regain and time to become apyrexial were measured and were found to be improved amongst immunotherapy recipients (P < 0·05).In the first month of treatment the levels of IgG to the 65 kDa and 70 kDa heat-shock proteins showed greater falls following immunotherapy (P < 0·05 and P < 0·001, respectively). On admission serum cytokine levels of interleukins 4 and 10 (IL-4, IL-10), interferon gamma (IFN-γ) and tumour necrosis factor alpha (TNF-α) were grossly raised in comparison with a matched control group (P < 0·001). After 1 month. Levels of IL-4, IL-10 and TNF-α fell (P < 0·001, P < 0·01 and P < 0·01, respectively) and levels of IFN-γ rose more (P = 0·005) in immunotherapy recipients than in those receiving chemotherapy alone. The results are in accord with a switch towards a TH1 immunological status and clinical benefit for immunotherapy recipients

Deaths in people from Black, Asian and minority ethnic communities from both COVID-19 and non-COVID causes in the first weeks of the pandemic in London: a hospital case note review

Objective To undertake a case review of deaths in a 6-week period during the COVID-19 pandemic commencing with the first death in the hospital from COVID-19 on 12th of March 2020 and contrast this with the same period in 2019. Setting A large London teaching hospital. Participants Three groups were compared: group 1—COVID-19-associated deaths in the 6-week period (n=243), group 2—non-COVID deaths in the same period (n=136) and group 3—all deaths in a comparison period of the same 6 weeks in 2019 (n=194). Primary and secondary outcome measures This was a descriptive analysis of death case series review and as such no primary or secondary outcomes were pre-stipulated. Results Deaths in patients from the Black, Asian and minority ethnic (BAME) communities in the pandemic period significantly increased both in the COVID-19 group (OR=2.43, 95% CI=1.60–3.68, p<0.001) and the non-COVID group (OR=1.76, 95% CI=1.09–2.83, p=0.02) during this time period and the increase was independent of differences in comorbidities, sex, age or deprivation. While the absolute number of deaths increased in 2020 compared with 2019, across all three groups the distribution of deaths by age was very similar. Our analyses confirm major risk factors for COVID-19 mortality including male sex, diabetes, having multiple comorbidities and background from the BAME communities. Conclusions There was no evidence of COVID-19 deaths occurring disproportionately in the elderly compared with non-COVID deaths in this period in 2020 and 2019. Deaths in the BAME communities were over-represented in both COVID-19 and non-COVID groups, highlighting the need for detailed research in order to fully understand the influence of ethnicity on susceptibility to illness, mortality and health-seeking behaviour during the pandemic

Identification of ER-000444793, a Cyclophilin D-independent inhibitor of mitochondrial permeability transition, using a high-throughput screen in cryopreserved mitochondria

Growing evidence suggests persistent mitochondrial permeability transition pore (mPTP) opening is a key pathophysiological event in cell death underlying a variety of diseases. While it has long been clear the mPTP is a druggable target, current agents are limited by off-target effects and low therapeutic efficacy. Therefore identification and development of novel inhibitors is necessary. To rapidly screen large compound libraries for novel mPTP modulators, a method was exploited to cryopreserve large batches of functionally active mitochondria from cells and tissues. The cryopreserved mitochondria maintained respiratory coupling and ATP synthesis, Ca(2+) uptake and transmembrane potential. A high-throughput screen (HTS), using an assay of Ca(2+)-induced mitochondrial swelling in the cryopreserved mitochondria identified ER-000444793, a potent inhibitor of mPTP opening. Further evaluation using assays of Ca(2+)-induced membrane depolarisation and Ca(2+) retention capacity also indicated that ER-000444793 acted as an inhibitor of the mPTP. ER-000444793 neither affected cyclophilin D (CypD) enzymatic activity, nor displaced of CsA from CypD protein, suggesting a mechanism independent of CypD inhibition. Here we identified a novel, CypD-independent inhibitor of the mPTP. The screening approach and compound described provides a workflow and additional tool to aid the search for novel mPTP modulators and to help understand its molecular nature

General anaesthetic and airway management practice for obstetric surgery in England: a prospective, multi-centre observational study

There are no current descriptions of general anaesthesia characteristics for obstetric surgery, despite recent changes to patient baseline characteristics and airway management guidelines. This analysis of data from the direct reporting of awareness in maternity patients' (DREAMY) study of accidental awareness during obstetric anaesthesia aimed to describe practice for obstetric general anaesthesia in England and compare with earlier surveys and best-practice recommendations. Consenting patients who received general anaesthesia for obstetric surgery in 72 hospitals from May 2017 to August 2018 were included. Baseline characteristics, airway management, anaesthetic techniques and major complications were collected. Descriptive analysis, binary logistic regression modelling and comparisons with earlier data were conducted. Data were collected from 3117 procedures, including 2554 (81.9%) caesarean deliveries. Thiopental was the induction drug in 1649 (52.9%) patients, compared with propofol in 1419 (45.5%). Suxamethonium was the neuromuscular blocking drug for tracheal intubation in 2631 (86.1%), compared with rocuronium in 367 (11.8%). Difficult tracheal intubation was reported in 1 in 19 (95%CI 1 in 16-22) and failed intubation in 1 in 312 (95%CI 1 in 169-667). Obese patients were over-represented compared with national baselines and associated with difficult, but not failed intubation. There was more evidence of change in practice for induction drugs (increased use of propofol) than neuromuscular blocking drugs (suxamethonium remains the most popular). There was evidence of improvement in practice, with increased monitoring and reversal of neuromuscular blockade (although this remains suboptimal). Despite a high risk of difficult intubation in this population, videolaryngoscopy was rarely used (1.9%)

Outcomes of the first 50 patients with abnormally invasive placenta managed using the "Triple P Procedure" conservative surgical approach.

OBJECTIVE: To determine maternal outcomes for women with abnormally invasive placenta (AIP) managed using the Triple P Procedure and establish its safety as a conservative surgical management option. METHODS: A retrospective study of the outcomes of the first 50 patients who underwent the Triple P Procedure for AIP from September 2010 to May 2017 at St George's Maternity Unit. Maternity case notes and the database were reviewed to determine the volume of bleeding, procedure-related complications, hysterectomy rate, and postoperative hospitalization. RESULTS: Mean operative blood loss was 2318 mL (range, 400-7300 mL and the incidence of bladder and ureteric injuries was 2% (n=1) and 0%, respectively. Median length of hospital stay was 4 days (range, 2-8 days). Three women (6.0%) developed arterial thrombosis without any long-term complications and none of the patients required peripartum hysterectomy. CONCLUSION: The Triple P Procedure should be considered as a conservative, less risky alternative to a peripartum hysterectomy during counselling prior to surgery for women with AIP