Iron Status Predicts Treatment Failure and Mortality in Tuberculosis Patients: A Prospective Cohort Study from Dar es Salaam, Tanzania

Experimental data suggest a role for iron in the course of tuberculosis (TB) infection, but there is limited evidence on the potential effects of iron deficiency or iron overload on the progression of TB disease in humans. The aim of the present analysis was to examine the association of iron status with the risk of TB progression and death.\ud We analyzed plasma samples and data collected as part a randomized micronutrient supplementation trial (not including iron) among HIV-infected and HIV-uninfected TB patients in Dar es Salaam, Tanzania. We prospectively related baseline plasma ferritin concentrations from 705 subjects (362 HIV-infected and 343 HIV-uninfected) to the risk of treatment failure at one month after initiation, TB recurrence and death using binomial and Cox regression analyses. Overall, low (plasma ferritin<30 µg/L) and high (plasma ferritin>150 µg/L for women and>200 µg/L for men) iron status were seen in 9% and 48% of patients, respectively. Compared with normal levels, low plasma ferritin predicted an independent increased risk of treatment failure overall (adjusted RR = 1.95, 95% CI: 1.07 to 3.52) and of TB recurrence among HIV-infected patients (adjusted RR = 4.21, 95% CI: 1.22 to 14.55). High plasma ferritin, independent of C-reactive protein concentrations, was associated with an increased risk of overall mortality (adjusted RR = 3.02, 95% CI: 1.95 to 4.67). Both iron deficiency and overload exist in TB patients and may contribute to disease progression and poor clinical outcomes. Strategies to maintain normal iron status in TB patients could be helpful to reduce TB morbidity and mortality

Prevalence of multimorbidity and its impact on survival in people with motor neuron disease

Background and purpose: This study was undertaken to determine the prevalence of multimorbidity in people with motor neuron disease (MND) and to identify whether specific patterns of multimorbidity impact survival beyond age alone.Methods: We performed a retrospective analysis of the Scottish national MND register from 1 January 2015 to 29 October 2019. People with amyotrophic lateral sclerosis, primary lateral sclerosis, progressive muscular atrophy, or progressive bulbar palsy were included. We fitted latent class regression models incorporating comorbidities (class indicators), age, sex, and bulbar onset (covariates), and survival (distal outcome) with multimorbidity as a hypothesised latent variable. We also investigated the association between the Charlson Comorbidity Index and survival in Cox regression and compared its discrimination and calibration to age alone.Results: A total of 937 people with MND were identified (median age = 67 years, 60.2% male); 64.8% (n = 515) had two or more comorbidities. We identified a subpopulation with high prevalence of cardiovascular disease, but when accounting for the relationship between age and individual comorbidities, there was no difference in survival. Both Charlson Comorbidity Index (hazard ratio [HR] per unit increase = 1.11, 95% confidence interval [CI] = 1.07-1.15, p &lt; 0.0001) and age (HR per year increase = 1.04, 95% CI = 1.03-1.05, p &lt; 0.0001) were significantly associated with survival, but discrimination was higher for age compared to Charlson Comorbidity Index (C-index = 0.63 vs. 0.59).Conclusions: Multimorbidity is common in MND, necessitating holistic interdisciplinary management, but age is the dominant predictor of prognosis in people with MND. Excluding people with MND and multimorbidity from trial participation may do little to homogenise the cohort in terms of survival potential and could harm generalisability.</p

Cleavage of E-Cadherin Contributes to Defective Barrier Function in Neosquamous Epithelium

BACKGROUND: After ablation of Barrett’s esophagus (BE), the esophagus heals with neosquamous epithelium (NSE). Despite normal endoscopic appearance, NSE exhibits defective barrier function with similarities to defects noted in the distal esophageal epithelium in patients with gas-troesophageal reflux disease (GERD). AIM: To determine whether patients with NSE, unlike patients with healthy esophageal epithelium, have C-terminal fragments (CTFs) of e-cad detectable on tissue biopsy. Secondly, to determine whether patients with NSE have elevated levels of N-terminal fragments (NTFs) of e-cad in the serum. METHODS: Fifteen patients with ablated long-segment BE, who had healing with formation of NSE, were enrolled in this pilot study. Western blots for CTFs and NTFs were performed on biopsies of NSE. Venous blood was obtained to assess levels of NTFs. Endoscopic distal esophageal biopsies from patients without esophageal disease served as tissue controls. Control blood samples were obtained from healthy subjects. RESULTS: Blots of NSE were successful in 14/15 patients, and all 14 (100 %) had a 35-kD CTF of e-cad, while CTFs were absent in healthy control tissues. Despite CTFs in NSE, serum NTFs of e-cad in NSE were similar to controls, p > 0.05. However, unlike healthy controls, blots of NSE also showed NTFs with molecular weights of 70–90 kD. CONCLUSIONS: Cleavage of e-cad, as evidenced by the presence of CTFs and NTFs on biopsy, contributes to defective barrier function in NSE. However, unlike findings reported in GERD patients, serum NTFs are not elevated in NSE patients. This difference may reflect poor absorption with tissue entrapment of NTFs in previously ablated areas with poorly perfused NSE