scholarly journals Plasma Biomarkers of Risk of Tuberculosis Recurrence in HIV Co-Infected Patients From South Africa

2021 ◽  
Vol 12 ◽  
Author(s):  
Kimesha Pillay ◽  
Lara Lewis ◽  
Santhuri Rambaran ◽  
Nonhlanhla Yende-Zuma ◽  
Derseree Archary ◽  
...  

There is an urgent need to identify immunological markers of tuberculosis (TB) risk in HIV co-infected individuals. Previously we have shown that TB recurrence in HIV co-infected individuals on ART was associated with markers of systemic inflammation (IL-6, IL1β and IL-1Rα). Here we examined the effect of additional acute inflammation and microbial translocation marker expression on risk of TB recurrence. Stored plasma samples were drawn from the TB Recurrence upon Treatment with HAART (TRuTH) study, in which individuals with previously treated pulmonary TB were screened for recurrence quarterly for up to 4 years. Recurrent TB cases (n = 37) were matched to controls (n = 102) by original trial study arm assignment and ART start date. Additional subsets of HIV infected (n = 41) and HIV uninfected (n = 37) individuals from Improving Recurrence Success (IMPRESS) study were sampled at active TB and post successful treatment completion. Plasma concentrations of soluble adhesion molecules (sMAdCAM, sICAM and sVCAM), lipopolysaccharide binding protein (LBP) and transforming growth factor-beta (TGF-β1, TGF-β2, TGF-β3) were measured by multiplex immunoassays and ELISA. Cytokine data was square root transformed in order to reduce variability. Multivariable analysis adjusted for a number of potential confounders measured at sample time-point: age, BMI, CD4 count, viral load (VL) and measured at baseline: presence or absence of lung cavities, previous history of TB, and WHO disease stage (4 vs 3). The following analytes were associated with increased risk of TB recurrence in the multivariable model: sICAM (aOR 1.06, 95% CI: 1.02-1.12, p = 0.009), LBP (aOR 8.78, 95% CI: 1.23-62.66, p = 0.030) and TGF-β3 (aOR 1.44, 95% CI 1.01-2.05, p = 0.044). Additionally, we observed a positive correlation between LBP and sICAM (r= 0.347, p<0.0001), and LBP and IL-6, identified to be one of the strongest predictors of TB risk in our previous study (r=0.623, p=0.03). These data show that increased risk of TB recurrence in HIV infected individuals on ART is likely associated with HIV mediated translocation of microbial products and the resulting chronic immune activation.

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Mazzanti ◽  
D Guz ◽  
A Trancuccio ◽  
E Pagan ◽  
T Chargeishvili ◽  
...  

Abstract Background Andersen-Tawil Syndrome type 1 (ATS1) in a rare arrhythmogenic disease caused by loss-of-function mutations in the KCNJ2 gene and characterized by ventricular arrhythmias, dysmorphic features and episodes of periodic paralysis. Although the prognosis of ATS1 patients is typically considered benign, definitive outcome data are lacking. Purpose We aimed to: 1) define the risk of life-threatening arrhythmic events (LAEs); 2) identify risk factors for such events; 3) assess the efficacy of anti-arrhythmic drugs in preventing LAEs. Methods We included 118 ATS1 patients from 57 families with confirmed pathogenic or likely pathogenic KCNJ2 mutations. Clinical and genetical data were acquired by investigators from 23 centers in 9 countries. Results Baseline characteristics of the population are presented in the Table. Over a follow-up of 6.2 years, 17/118 (14%) patients experienced a first LAE, with a 5-year cumulative probability of 7.9% (Figure). Cox multivariable analysis demonstrated that a previous history of syncope (HR 4.5, p=0.02), the documentation of sustained VT (HR 9.3, p=0.001) and the administration of amiodarone (HR 268, p<0.001) were associated with an increased risk of LAE. The baseline rate of LAE was not reduced by beta-blockers alone (1.37 per 100 py; p=1), or in combination with class Ic antiarrhythmic drugs (1.46 per 100 py, p=1). Conclusions Our data demonstrate that the clinical course of patients with ATS1 is characterized by a high rate of LAE. A history of unexplained syncope, and documentation of sustained ventricular tachycardia are independently associated with a higher risk of LAE. Amiodarone is proarrhythmic and should be avoided in ATS1 patients. ATS1: Diagnosis, Outcome, Risk Factors Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): ERN Guard-Heart European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Lee ◽  
E K Choi ◽  
K D Han ◽  
S Oh

Abstract Background Bodyweight fluctuation is a risk factor for cardiovascular events and death. We investigated whether bodyweight variability is also a risk factor for atrial fibrillation (AF) development. Methods A nationwide population-based cohort of 8,091,401 adults from the Korean National Health Insurance Service database without previous history of AF and with at least 3 measurements of bodyweight over a 5-year period was followed up for incident AF. Intra-individual bodyweight variability was calculated using variability independent of mean, and high bodyweight variability was defined as the quartile with highest bodyweight variability (Q4) with Q1–3 as reference. Results During median 8.1 years of follow-up, AF was newly diagnosed in 158,347 (2.0%). Increasing bodyweight variability was associated with AF development after adjustment for baseline bodyweight, height, age, sex, lifestyle factors and comorbidities: each increase of 1-SD in bodyweight variability was associated with 5% increased risk of AF development (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.04–1.05), and subjects with highest bodyweight variability (Q4) showed 14% increased risk of AF development compared to those in the quartile with lowest bodyweight variability (HR 1.14, 95% CI 1.12–1.15). When the cohort was grouped by body mass index (BMI) into underweight, normal weight, overweight, obese (Figure 1A), subjects with high bodyweight variability showed a shallow U-shaped relationship of BMI with AF incidence, with the highest incidence rate of AF in the underweight group. On the other hand, subjects with reference bodyweight variability showed a proportional increase of AF incidence with BMI, with the highest AF incidence in the obese group. High bodyweight variability was significantly associated with AF development in all BMI groups except in the very obese (BMI≥30) in multivariable analysis, and this association was stronger in subjects with lower bodyweight. In underweight subjects, high bodyweight variability was associated with 16% increased risk of AF development (HR 1.16, 95% CI 1.08–1.24). Obese subjects with high bodyweight variability compared to those with reference variability showed lower crude AF incidence rates, but after multivariable analysis, AF risk was increased (obese stage I) or comparable (obese stage II). When the cohort was grouped by total bodyweight change (Figure 1B), subjects with high bodyweight variability showed higher AF incidence and elevated AF risk on multivariable analysis in all weight change groups. Subjects with overall weight loss (≥-5%) and high bodyweight variability showed the highest AF incidence and AF risk (HR 1.12, 95% CI 1.09–1.15). Figure 1 Conclusions Fluctuation in bodyweight was independently associated with higher risk of AF development. The association of high bodyweight variability with AF development was especially stronger in subjects with lower bodyweight, and in subjects with overall weight loss (≥-5%)


2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Rayra P. Santiago ◽  
Camylla V. B. Figueiredo ◽  
Luciana M. Fiuza ◽  
Sètondji C. M. A. Yahouédéhou ◽  
Rodrigo M. Oliveira ◽  
...  

Individuals with sickle cell disease (SCD) present both chronic and acute inflammatory events. The TGF-β pathway is known to play a role in immune response, angiogenesis, inflammation, hematopoiesis, vascular inflammation, and cell proliferation. Polymorphisms in the transforming growth factor-beta receptor 3 (TGFBR3) gene have been linked to several inflammatory diseases. This study investigated associations between two TGFBR3 haplotypes and classical laboratory parameters, as well as clinical manifestations, in SCD. We found that individuals with the GG haplotype presented higher levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides, non-HDL cholesterol, total proteins, and globulin than individuals with non-GG haplotypes. In addition, the GG haplotype was associated with a previous history of pneumonia. Individuals with the CGG haplotype presented increased plateletcrit, TC, LDL-C levels, and non-HDL cholesterol. The CCG haplotype was also associated with a previous history of pneumonia. Our findings suggest that individuals with the GG and CGG haplotypes of TGFBR3 present important alterations in lipid profile.


2022 ◽  
Vol 24 (1) ◽  
Author(s):  
Tal Gazitt ◽  
Jacob Pesachov ◽  
Idit Lavi ◽  
Muna Elias ◽  
Amir Haddad ◽  
...  

Abstract Background Although the risk of cardiovascular disease has been discussed extensively in both psoriasis (PsO) and psoriatic arthritis (PsA), very few studies have addressed the occurrence of venous thromboembolic (VTE) events among PsO patients, and even fewer in PsA. Thus, our goal was to assess the association between PsA and VTE events using a large population-based database. Methods This retrospective cohort study includes all 5,275 patients with newly diagnosed PsA from the largest health care provider in Israel between January 2003 and December 2018. Identified PsA patients were matched by age, sex, ethnicity, and index date with 21,011 controls without PsA from the same database. Both groups were followed through June 30, 2019 for the occurrence of VTE event. Cox proportional hazard regression models were used to assess the association between PsA and VTE. Results PsA cohort consisted of 53.2% females with mean age of 51.7±15.4 Sixty-two patients (1.2%) were diagnosed with VTE in the PsA group and 176 patients (0.8%) in the control group (p=0.023, HR=1.40, 95% CI 1.05-1.87). However, there was no increased risk of VTE among PsA patients on multivariable analysis (p=0.16, HR=1.27, 95% CI 0.91-1.80). Within the PsA group, patients with VTE were more often of older age and with history of VTE. Conclusions This study suggests that the increased risk of VTE in PsA patients appears to be related to the underlying comorbidities and not independently associated with PsA. Age and previous history of VTE were the only risk factors associated with increased risk of VTE in patients with PsA. Addressing VTE risk is recommended especially in the era of Janus kinase inhibitors.


2021 ◽  
Vol 11 (3) ◽  
pp. 178
Author(s):  
Noah R. Delapaz ◽  
William K. Hor ◽  
Michael Gilbert ◽  
Andrew D. La ◽  
Feiran Liang ◽  
...  

Post-traumatic stress disorder (PTSD) is a prevalent mental disorder marked by psychological and behavioral changes. Currently, there is no consensus of preferred antipsychotics to be used for the treatment of PTSD. We aim to discover whether certain antipsychotics have decreased suicide risk in the PTSD population, as these patients may be at higher risk. A total of 38,807 patients were identified with a diagnosis of PTSD through the ICD9 or ICD10 codes from January 2004 to October 2019. An emulation of randomized clinical trials was conducted to compare the outcomes of suicide-related events (SREs) among PTSD patients who ever used one of eight individual antipsychotics after the diagnosis of PTSD. Exclusion criteria included patients with a history of SREs and a previous history of antipsychotic use within one year before enrollment. Eligible individuals were assigned to a treatment group according to the antipsychotic initiated and followed until stopping current treatment, switching to another same class of drugs, death, or loss to follow up. The primary outcome was to identify the frequency of SREs associated with each antipsychotic. SREs were defined as ideation, attempts, and death by suicide. Pooled logistic regression methods with the Firth option were conducted to compare two drugs for their outcomes using SAS version 9.4 (SAS Institute, Cary, NC, USA). The results were adjusted for baseline characteristics and post-baseline, time-varying confounders. A total of 5294 patients were eligible for enrollment with an average follow up of 7.86 months. A total of 157 SREs were recorded throughout this study. Lurasidone showed a statistically significant decrease in SREs when compared head to head to almost all the other antipsychotics: aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone (p < 0.0001 and false discovery rate-adjusted p value < 0.0004). In addition, olanzapine was associated with higher SREs than quetiapine and risperidone, and ziprasidone was associated with higher SREs than risperidone. The results of this study suggest that certain antipsychotics may put individuals within the PTSD population at an increased risk of SREs, and that careful consideration may need to be taken when prescribed.


2021 ◽  
Vol 6 (1) ◽  
pp. e000639
Author(s):  
Danielle Ní Chróinín ◽  
Nevenka Francis ◽  
Pearl Wong ◽  
Yewon David Kim ◽  
Susan Nham ◽  
...  

BackgroundGiven the increasing numbers of older patients presenting with trauma, and the potential influence of delirium on outcomes, we sought to investigate the proportion of such patients who were diagnosed with delirium during their stay—and patient factors associated therewith—and the potential associations between delirium and hospital length of stay (LOS). We hypothesized that delirium would be common, associated with certain patient characteristics, and associated with long hospital LOS (highest quartile).MethodsWe conducted a retrospective observational cohort study of all trauma patients aged ≥65 years presenting in September to October 2019, interrogating medical records and the institutional trauma database. The primary outcome measure was occurrence of delirium.ResultsAmong 99 eligible patients, delirium was common, documented in 23% (23 of 99). On multivariable analysis, adjusting for age, frailty and history of dementia, frailty (OR 4.09, 95% CI 1.08 to 15.53, p=0.04) and dementia (OR 5.23, 95% CI 1.38 to 19.90, p=0.02) were independently associated with likelihood of delirium. Standardized assessment tools were underused, with only 34% (34 of 99) screened within 4 hours of arrival. On univariate logistic regression analysis, having an episode of delirium was associated with long LOS (highest quartile), OR of 5.29 (95% CI 1.92 to 14.56, p<0.001). In the final multivariable model, adjusting for any (non-delirium) in-hospital complication, delirium was independently associated with long LOS (≥16 days; OR 4.81, p=0.005).DiscussionIn this study, delirium was common. History of dementia and baseline frailty were associated with increased risk. Delirium was independently associated with long LOS. However, many patients did not undergo standardized screening at admission. Early identification and targeted management of older patients at risk of delirium may reduce incidence and improve care of this vulnerable cohort. These data are hypothesis generating, but support the need for initiatives which improve delirium care, acknowledging the complex interplay between frailty and other geriatric syndromes in the older trauma patients.Level of evidenceIII.


Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Yu Kang ◽  
Srinivas Denduluri ◽  
Bruna M Assuncao ◽  
Marielle Scherrer-Crosbie

Introduction: The incidence of acute leukemia has been increasing by about 1.6% per year in the last decade. Anthracyclines remain a standard of care for patients with acute leukemia; survival is increasing at about 1.0% per year. However, little is known about the incidence and risk of major adverse cardiovascular events (MACE) in patients with acute leukemia. Hypothesis: To investigate the incidence of MACE and the risk factors for MACE in patients with acute leukemia treated with anthracyclines. Methods: All adult patients with acute leukemia treated with anthracyclines between January 2005 and April 2018 at the hospital of University of Pennsylvania were studied. MACE were defined as cardiovascular death, symptomatic heart failure, non-fatal acute coronary syndrome, non-fatal ventricular arrhythmia and non-fatal ischemic stroke. Differences between patients with or without MACE were compared by Student’s t test or the Wilcoxon rank comparison. Cox proportional hazard analysis was used to determine significant clinical and echocardiographic parameters associated with MACE. Results: Six hundred and seventy-four patients (234 acute lymphoblastic leukemia (ALL), 440 acute myeloid leukemia (AML), age range: 22 to 93 years) were studied. Seventy-one patients (10.5%) experienced MACEs during a median follow-up period of 16 months (4 to 146 months) after the initiation of chemotherapy. The median time to MACE was 13 months (5 to 107 months). In the patients with MACE,59 (8.8%) developed symptomatic heart failure, 7 (1.0%) died of cardiovascular causes, 3 (0.4%) experienced non-fatal acute myocardial syndrome and 2 (0.3%) had an ischemic stroke. The Table summarizes the characteristics of patients with and without MACE. In a multivariable analysis, a previous history of heart failure (HR: 4.632, P=0.000, 95% CI: 2.572-8.341), leukemia type (HR: 3.155, P=0.002, 95% CI: 1.544-6.446) and baseline LVEF (HR: 0.973, P=0.000, 95% CI: 0.955-0.991) remained associated with MACE. Conclusion: Patients with acute leukemia treated with anthracyclines have a high rate of MACE after chemotherapy. A previous history of heart failure, baseline LVEF and type of leukemia may help to stratify acute leukemia patients at highest risk for MACEs after anthracycline therapy.


2020 ◽  
Vol 4 (FI1) ◽  
pp. 1-6 ◽  
Author(s):  
Gianfranco Mitacchione ◽  
Marco Schiavone ◽  
Alessio Gasperetti ◽  
Giovanni B Forleo

Abstract Background Coronavirus disease 2019 (COVID-19) has been associated with myocardial involvement. Among cardiovascular manifestations, cardiac arrhythmias seem to be fairly common, although no specifics are reported in the literature. An increased risk of malignant ventricular arrhythmias and electrical storm (ES) has to be considered. Case summary We describe a 68-year-old patient with a previous history of coronary artery disease and severe left ventricular systolic disfunction, who presented to our emergency department describing cough, dizziness, fever, and shortness of breath. She was diagnosed with COVID-19 pneumonia, confirmed after three nasopharyngeal swabs. Ventricular tachycardia (VT) storm with multiple implantable cardioverter defibrillator (ICD) shocks was the presenting manifestation of cardiac involvement during the COVID-19 clinical course. A substrate-based VT catheter ablation procedure was successfully accomplished using a remote navigation system. The patient recovered from COVID-19 and did not experience further ICD interventions. Discussion To date, COVID-19 pneumonia associated with a VT storm as the main manifestation of cardiac involvement has never been reported. This case highlights the role of COVID-19 in precipitating ventricular arrhythmias in patients with ischaemic cardiomyopathy who were previously stable.


Blood ◽  
2020 ◽  
Author(s):  
Fadi Fakhouri ◽  
Marc Fila ◽  
Aurelie Hummel ◽  
David Ribes ◽  
Anne-Laure Sellier-Leclerc ◽  
...  

The optimal duration of eculizumab treatment in patients with atypical haemolytic uremic syndrome (aHUS) remains poorly defined. We conducted a prospective national multicentric open-label study in order to assess eculizumab discontinuation in children and adults with aHUS. Fifty-five patients (including 19 children) discontinued eculizumab (mean duration of treatment, 16.5 months). Twenty-eight (51%) patients had complement gene rare variants, mostly in MCP (n= 12, 22%), CFH (n= 6, 11%) and CFI (n=6, 10%) genes. At eculizumab discontinuation, 17 (30%) and 4 (7%) patients had chronic kidney disease stage 3 and 4, respectively. During follow-up, 13 (23%) patients (6 children and 7 adults) experienced aHUS relapse. In multivariable analysis, female gender and the presence of a rare complement gene variant were associated with an increased risk of aHUS relapse, whereas requirement for dialysis during previous episodes of acute aHUS was not. In addition, an increased soluble C5b-9 plasma level at eculizumab discontinuation was associated with a higher risk of aHUS relapse in all patients and in the subset of carriers of complement gene rare variants, in log rank test and in multivariable analysis. Among the 13 relapsing patients, who were all restarted on eculizumab, 11 regained their baseline renal function and two had a worsening of their pre-existing chronic kidney disease, including one patient who progressed to end-stage renal disease. A strategy of eculizumab discontinuation in aHUS patients based on complement genetics is reasonable and safe. It improves the management and quality of life of a sizeable proportion of aHUS patients while reducing the cost of treatment. Trail registration number: NCT02574403.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Marina Njelekela ◽  
Alfa Muhihi ◽  
Akum Aveika ◽  
Donna Spiegelman ◽  
Claudia Hawkins ◽  
...  

Background. Elevated blood pressure has been reported among treatment naïve HIV-infected patients. We investigated prevalence of hypertension and its associated risk factors in a HAART naïve HIV-infected population in Dar es Salaam, Tanzania.Methods. A cross-sectional analysis was conducted among HAART naïve HIV-infected patients. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg. Overweight and obesity were defined as body mass index (BMI) between 25.0–29.9 kg/m2and ≥30 kg/m2, respectively. We used relative risks to examine factors associated with hypertension.Results. Prevalence of hypertension was found to be 12.5%. After adjusting for possible confounders, risk of hypertension was 10% more in male than female patients. Patients aged ≥50 years had more than 2-fold increased risk for hypertension compared to 30–39-years-old patients. Overweight and obesity were associated with 51% and 94% increased risk for hypertension compared to normal weight patients. Low CD4+ T-cell count, advanced WHO clinical disease stage, and history of TB were associated with 10%, 42%, and 14% decreased risk for hypertension.Conclusions. Older age, male gender, and overweight/obesity were associated with hypertension. Immune suppression and history of TB were associated with lower risk for hypertension. HIV treatment programs should screen and manage hypertension even in HAART naïve individuals.


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