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Tuberculosis and Increased Incidence of Cardiovascular Disease: Cohort Study Using United States and United Kingdom Health Records.
Get PDFBACKGROUND: Limited evidence suggests elevated risks of cardiovascular disease (CVD) among people diagnosed with tuberculosis (TB) disease, though studies have not adjusted for preexisting CVD risk. We carried out a cohort study using 2 separate datasets, estimating CVD incidence in people with TB versus those without. METHODS: Using data from the United States (Veterans Health Administration) and the United Kingdom (Clinical Practice Research Datalink) for 2000-2020, we matched adults with incident TB disease and no CVD history 2 years before TB diagnosis (US, n = 2121; UK, n = 15 820) with up to 10 people without TB on the basis of age, sex, race/ethnicity and healthcare practice. Participants were followed beginning 2 years before TB diagnosis and for 2 years subsequently. The acute period was defined as 3 months before/after TB diagnosis. TB, CVD, and covariates were identified from electronic routinely collected data (primary and secondary care; mortality). Poisson models estimated incident rate ratios for CVD events in people with TB compared to those without. RESULTS: CVD incidence was consistently higher in people with TB, including during the baseline period (pre-TB) and particularly in the acute period: incident rate ratios were US, 3.5 (95% confidence interval, 2.7-4.4), and UK, 2.7 (2.2-3.3). Rate ratios remained high after adjusting for differences in preexisting CVD risk: US, 3.2 (2.2-4.4); UK, 1.6 (1.2-2.1). CONCLUSIONS: Increased CVD incidence was observed in people with TB versus those without, especially within months of TB diagnosis, persistent after adjustment for differences in preexisting risk. Enhancing CVD screening and risk management may improve long-term outcomes in people with TB
Impact of HIV Status on Group B Streptococcus Colonization and Antibody Responses in Serum and Vaginal Mucosa
No full textBackground:
Group B streptococcus (GBS) is a commensal bacterium of the digestive and genital tracts that can occasionally cause maternal and neonatal disease. GBS is particularly a burden in low-resource settings, where infections with HIV are also highly prevalent. This study investigates the impact of HIV status on GBS colonization and antibody levels.
Methods:
In Uganda, 90 nonpregnant women of childbearing age were followed for 3 months. Every 2 weeks, rectal and vaginal swabs were tested for GBS, and vaginal cups and blood were collected for measurement of GBS capsular polysaccharides (CPS) IgG using standardized assays.
Results:
Twenty-six of 90 women were living with HIV. Almost 51/90 women were GBS colonized at 1 or several visits. GBS colonization fluctuated in the rectal and vaginal sites. Most prevalent serotypes were Ia and III, with 33 individuals carrying different serotypes over time. Serum and vaginal CPS-IgG levels were stable over 12 weeks. In serum, for serotypes Ib–V, the geometric mean concentration (GMC) of CPS-IgG did not differ between HIV+ and HIV− participants. However, the GMC for serum CPS-Ia-IgG in the HIV+ group was 2.5 times lower than in the HIV− group (P = 0.038). Vaginal CPS-IgG was measurable in 5/26 (19%) HIV+ participants, and 32/64 (50%) HIV− participants.
Conclusions:
Despite fluctuating GBS colonization, antibody levels remained stable over 12 weeks. The level of CPS-Ia-specific IgG in serum was lower in women with HIV than in those without HIV. Vaginal CPS-specific IgG was not measurable in 81% of individuals with HIV
Research exposure in UK paediatric training: how do we address the gaps-experience from the London REACH network.
Get PDFTrainee-led Research Networks (TRNs) can mitigate against the lack of in-training academic opportunities by offering research experience, support and shared learning for paediatricians. The London Research, Evaluation and Audit for Child Health (REACH) Network, founded in 2021, has grown to involve a diverse group of 190 volunteer members at 28 London hospitals. Planning and delivery of a range of multisite projects bring not only many challenges but also a wealth of learning opportunities relating to research and quality improvement as well as leadership, management, education and fostering an accessible and equitable research culture. TRNs are an effective and valuable tool in improving the experience of trainees
Single-cycle parainfluenza virus type 5 vectors for producing recombinant proteins, including a humanized anti-V5 tag antibody.
Get PDFParainfluenza virus type 5 (PIV5) can cause either persistent or acute/lytic infections in a wide range of mammalian tissue culture cells. Here, we have generated PIV5 fusion (F)-expressing helper cell lines that support the replication of F-deleted viruses. As proof of the principle that F-deleted single-cycle infectious viruses can be used as safe and efficient expression vectors, we have cloned and expressed a humanized (Hu) version of the mouse anti-V5 tag antibody (clone SV5-Pk1). We show that multiple different cell lines can be infected and express high levels of the Hu anti-V5 antibody, with Chinese hamster ovary cells expressing 20-50 mg l-1 after 5 days when cells were grown to a density of ~1×106 cells per millilitre at the time of infection. We suggest that PIV5-based vectors may be further developed to produce recombinant proteins both in vitro and in vivo
Clinical derivation and data simulated validation of rule-out and rule-in algorithms for the Siemens Atellica IM high-sensitivity cardiac troponin I assay.
Get PDFBACKGROUND: This prospective, two-centre study derived and validated predictive algorithms for the Siemens Atellica IM high-sensitivity cardiac troponin I (hs-cTnI) assay in the emergency department (ED). METHODS: Algorithms for predicting 30-day myocardial infarction type 1 and 2 (MI) and death or non-ST-elevation myocardial infarction (NSTEMI, type 1 and 2) at index admission were developed from a derivation cohort of 1896 patients and validated using a synthetic dataset with nearly 1 million patient cases. Performance was compared to the European Society of Cardiology algorithms for hs-cTnT (Roche Diagnostics) and hs-cTnI (Abbott Diagnostics). RESULTS: An admission hs-cTnI concentration 96% for 30-day MI or death and index NSTEMI. The results were comparable to established hs-cTn algorithms. CONCLUSIONS: This study presents Siemens Atellica hs-cTnI algorithms for diagnosis and risk-prediction in the ED with performance comparable to established hs-cTnT (Roche) and hs-cTnI (Abbott) algorithms
Ischemic Stroke Prevention in Patients Atrial Fibrillation and a Recent Ischemic Stroke, TIA, or Intracranial Hemorrhage; a World Stroke Organisation (WSO) Scientific Statement.
Get PDFBACKGROUND: Secondary stroke prevention in patients with atrial fibrillation (AF) is one of the fastest growing areas in the field of cerebrovascular diseases. This Scientific statement from the World Stroke Organization Brain & Heart Task Force provides a critical analysis of the strength of current evidence this topic, highlights areas of current controversy, identifies knowledge gaps, and proposes priorities for future research. METHODS: We select topics with the highest clinical relevance and perform a systematic search to answer specific practical questions. Based on the strength of available evidence and knowledge gaps, we identify topics that need to be prioritized in future research. For this purpose, we adopt a novel classification of evidence strength based on the availability of publications in which the primary population is patients with recent (<6 months) cerebrovascular events, whether the primary study endpoint is a recurrent ischemic stroke, and the quality of the studies (e.g., observational vs. randomized controlled trial). SUMMARY: Priority areas include AF screening, molecular biomarkers, AF subtype classification, anticoagulation in device-detected AF, timing of anticoagulation initiation, effective management of breakthrough strokes on existing anticoagulant therapy, the role of left atrial appendage closure, novel approaches, and antithrombotic therapy post-intracranial hemorrhage. Strength of currently available evidence varies across the selected topics, with early anticoagulation being the one showing more consistent data. CONCLUSION: Several knowledge gaps persist in most areas related to secondary stroke prevention in AF. Prioritizing research in this field is crucial to advance current knowledge and improve clinical care
Reassessing the need for primary prevention implantable cardioverter-defibrillators in contemporary patients with heart failure.
No full textThe main function of the implantable cardioverter-defibrillator (ICD) is to protect against sudden cardiac death (SCD) due to ventricular tachyarrhythmia (VTA). Current guidelines provide a recommendation to implant a prophylactic ICD for the primary prevention of SCD in individuals having heart failure with reduced ejection fraction (HFrEF) who never experienced a previous sustained VTA. However, these recommendations are based on clinical trials conducted more than 20 years ago and may not be applicable to contemporary patients with HFrEF who have a lower arrhythmic risk as a result of advances in heart failure medical therapies. Thus, there is an unmet need for more appropriate selection of contemporary patients with HFrEF for a primary prevention ICD. In this article, we review data underlying the current clinical equipoise on the need for routine implantation of a primary prevention ICD in patients with HFrEF and the rationale for conducting clinical trials that aim to reassess the role of the ICD in this population
Exploring specific alterations at the explicit and perceptual levels in sense of ownership, agency, and body schema in Functional Motor Disorder: A pilot comparative study with Irritable Bowel Syndrome.
Get PDFFunctional Motor Disorders (FMD) consists in symptoms of altered motor function not attributable to typical neurological and medical conditions. This study aimed to explore explicit and perceptual measures of Sense of Ownership, Agency, and Body Schema in FMD patients, and assess whether these alterations are specific to FMD or shared with other functional disturbances. Twelve FMD patients, ten with Irritable Bowel Syndrome (IBS, a functional gastrointestinal disorder) and fifteen healthy controls (HC) underwent: (i) the Mirror Box Illusion (MBI), requiring participants to perform tapping movements with their dominant hand concealed from sight, while visual feedback was provided by an alien hand under visuo-motor congruency or incongruency conditions; (ii) a Forearm Bisection Task before and after exposure to the MBI, and the Embodiment Questionnaire after the MBI, as perceptual and explicit indices of the embodiment illusion, respectively. At the Embodiment Questionnaire, all groups self-reported embodiment of the alien hand only under visuo-motor congruency; at the perceptual level, HC showed the expected distalized drift (an "elongated" arm in the Body Schema) under visuo-motor congruency, while FMD and IBS patients did not. FMD patients showed a proximalized drift when sensory feedback mismatched, possibly reflecting reliance on altered priors to avoid losing control over their movement. Results in IBS patients suggest Body Schema alterations differ across functional syndromes. In conclusion, we found that explicit Sense of Ownership and Agency are preserved in FMD and IBS patients, but dissociate from their implicit measures, differing in degree according to the specific disturbance
Stanniocalcin-1: A Novel Mediator in Diabetic Kidney Disease and Cardiovascular Disease.
Get PDFDiabetes mellitus represents a group of metabolic diseases characterized by hyperglycemia from defects in insulin secretion, action, or both. The prevalence of type 2 diabetes mellitus, characterized by insulin resistance, has increased over time in the UK, and is the most prevalent cause of chronic kidney disease (CKD). Cardiovascular complications are a major cause of mortality for these patients. Stanniocalcin (STC), originally identified in bony fish as a hormone regulating calcium levels, has since been found in mammals, including humans. In fish, STC functions as an antihypercalcemic factor. Mammals possess 2 STC orthologues, STC-1 and STC-2, with STC-1 demonstrating significant sequence and functional conservation across species. Unlike fish, STC-1 is not normally present in the blood of healthy humans. However, it can be detected in certain conditions such as pregnancy, cancer, and CKD. In humans, STC-1 has diverse roles, including modulation of calcium and phosphate homeostasis, and it is implicated in kidney and cardiovascular protection. It has been reported that STC-1 has antioxidant, anti-inflammatory, and antiapoptotic activities, playing a role in renoprotection in diabetic nephropathy. This review explores the molecular biology of STC-1, its physiological functions, and its emerging role in GKDs, particularly diabetic and cardiovascular diseases. We highlight its potential protective mechanisms against hypercalcemia, its antioxidant and anti-inflammatory properties, and its cardioprotective properties in ischemia-reperfusion. Further research into STC-1 could provide new insights into therapeutic strategies for managing diseases characterized by calcium imbalance and lead to new treatments for the cardiovascular morbidity associated with diabetic kidney disease
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