Sputum is a surrogate for bronchoalveolar lavage for monitoring Mycobacterium tuberculosis transcriptional profiles in TB patients

SummaryPathogen-targeted transcriptional profiling in human sputum may elucidate the physiologic state of Mycobacterium tuberculosis (M. tuberculosis) during infection and treatment. However, whether M. tuberculosis transcription in sputum recapitulates transcription in the lung is uncertain. We therefore compared M. tuberculosis transcription in human sputum and bronchoalveolar lavage (BAL) samples from 11 HIV-negative South African patients with pulmonary tuberculosis. We additionally compared these clinical samples with in vitro log phase aerobic growth and hypoxic non-replicating persistence (NRP-2). Of 2179 M. tuberculosis transcripts assayed in sputum and BAL via multiplex RT-PCR, 194 (8.9%) had a p-value <0.05, but none were significant after correction for multiple testing. Categorical enrichment analysis indicated that expression of the hypoxia-responsive DosR regulon was higher in BAL than in sputum. M. tuberculosis transcription in BAL and sputum was distinct from both aerobic growth and NRP-2, with a range of 396–1020 transcripts significantly differentially expressed after multiple testing correction. Collectively, our results indicate that M. tuberculosis transcription in sputum approximates M. tuberculosis transcription in the lung. Minor differences between M. tuberculosis transcription in BAL and sputum suggested lower oxygen concentrations or higher nitric oxide concentrations in BAL. M. tuberculosis-targeted transcriptional profiling of sputa may be a powerful tool for understanding M. tuberculosis pathogenesis and monitoring treatment responses in vivo

The Association between the Five-Minute Apgar Score and Neurodevelopmental Outcomes among Children Aged 8−66 Months in Australia

This study aimed to evaluate the association of the five-minute Apgar score and neurodevelopmental outcomes in children by taking the entire range of Apgar scores into account. Data from the Australian Longitudinal Study of Women’s Health (ALSWH) and Mothers and their Children’s Health (MatCH) study were linked with Australian state-based Perinatal Data Collections (PDCs) for 809 children aged 8−66 months old. Generalized estimating equations were used to model the association between the five-minute Apgar scores and neurodevelopmental outcomes, using STATA software V.15. Of the 809 children, 614 (75.3%) had a five-minute Apgar score of 9, and 130 (16.1%) had an Apgar score of 10. Approximately 1.9% and 6.2% had Apgar scores of 0−6 and 7−8, respectively. Sixty-nine (8.5%) of children had a neurodevelopmental delay. Children with an Apgar score of 0−6 (AOR = 5.7; 95% CI: 1.2, 27.8) and 7−8 (AOR = 4.1; 95% CI: 1.2, 14.1) had greater odds of gross-motor neurodevelopment delay compared to children with an Apgar score of 10. Further, when continuously modelled, the five-minute Apgar score was inversely associated with neurodevelopmental delay (AOR = 0.75; 95% CI: 0.60, 0.93). Five-minute Apgar score was independently and inversely associated with a neurodevelopmental delay, and the risks were higher even within an Apgar score of 7−8. Hence, the Apgar score may need to be taken into account when evaluating neurodevelopmental outcomes in children

Patterns of contraceptive use through later reproductive years: A cohort study of Australian women with chronic disease.

BackgroundPregnancies among women with chronic disease are associated with poor maternal and fetal outcomes. There is a need to understand how women use or don't use contraception across their reproductive years to better inform the development of preconception care strategies to reduce high risk unintended pregnancies, including among women of older reproductive age. However, there is a lack of high-quality longitudinal evidence to inform such strategies. We examined patterns of contraceptive use among a population-based cohort of reproductive aged women and investigated how chronic disease influenced contraceptive use over time.Methods and findingsContraceptive patterns from 8,030 women of reproductive age from the Australian Longitudinal Study on Women's Health (1973-78 cohort), who were at potential risk of an unintended pregnancy were identified using latent transition analysis. Multinomial mixed-effect logistic regression models were used to evaluate the relationship between contraceptive combinations and chronic disease. Contraception non-use increased between 2006 and 2018 but was similar between women with and without chronic disease (13.6% vs. 12.7% among women aged 40-45 years in 2018). When specific contraceptive use patterns were examined over time, differences were found for women with autoinflammatory diseases only. These women had increased odds of using condom and natural methods (OR = 1.20, 95% CI = 1.00, 1.44), and sterilisation and other methods (OR = 1.61, 95% CI = 1.08, 2.39) or no contraception (OR = 1.32, 95% CI = 1.04, 1.66), compared to women without chronic disease using short-acting methods and condoms.ConclusionPotential gaps in the provision of appropriate contraceptive access and care exist for women with chronic disease, particularly for women diagnosed with autoinflammatory conditions. Development of national guidelines as well as a clear coordinated contraceptive strategy that begins in adolescence and is regularly reviewed during care management through their main reproductive years and into perimenopause is required to increase support for, and agency among, women with chronic disease

A pilot study of inflammatory mediators in brain extracellular fluid in paediatric TBM.

Tuberculous meningitis (TBM) is the most fatal form of tuberculosis and frequently occurs in children. The inflammatory process initiates secondary brain injury processes that lead to death and disability. Much remains unknown about this cerebral inflammatory process, largely because of the difficulty in studying the brain. To date, studies have typically examined samples from sites distal to the site of disease, such as spinal cerebrospinal fluid (CSF) and blood. In this pilot study, we examined the feasibility of using direct brain microdialysis (MD) to detect inflammatory mediators in brain extracellular fluid (ECF) in TBM. MD was used to help guide neurocritical care in 7 comatose children with TBM by monitoring brain chemistry for up to 4 days. Remnant ECF fluid was stored for offline analysis. Samples of ventricular CSF, lumbar CSF and blood were collected at clinically indicated procedures for comparison. Inflammatory mediators were quantified using multiplex technology. All inflammatory markers, with the exception of interleukin (IL)-10 and IL-12p40, were detected in the ECF. Cytokine concentrations were generally lower in ECF than ventricular CSF in time-linked specimens. Individual cases showed ECF cytokine increases coinciding with marked increases in ECF glycerol or decreases in ECF glucose. Cytokine levels and glycerol were generally higher in patients with more severe disease. This is the first report of inflammatory marker analysis from samples derived directly from the brain and in high temporal resolution, demonstrating feasibility of cerebral MD to explore disease progression and possibly therapy response in TBM

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research