Effect of malnutrition on tuberculosis microbiologic severity in India

The relationship between malnutrition and tuberculosis disease (TB) severity is understudied. This study analyzed data collected by a large cohort study to investigate the effect malnutrition, measured by BMI, had on TB mycobacterial burden. A study population of 538 subjects was utilized for this secondary data analysis. Multivariate negative binomial regression was used to evaluate relationships between body mass index (BMI) categories and mycobacterial growth indicator tube (MGIT) days to positive. Of the 538 subjects, 79% were male and 21% were female. The median age was 45 years of age. One subject was HIV seropositive and was excluded from the final analysis. There were incomplete outcome data for 63 subjects, who were excluded from the final analysis. BMI was categorized as severe malnutrition (BMI<16.5 kg/m2), malnutrition (16.5≤BMI<18.5), normal (18.5≤BMI<25), and overweight/obese (BMI≥25), with 27%, 32%, 36%, and 5% of the population comprising these categories, respectively. The median MGIT days to positive was 8 days. After adjusting for confounders, individuals who had severe malnutrition or malnutrition had an adjusted RR of 1.05 (95% CI, 0.90–1.23) and 1.08 (95% CI, 0.94, 1.24), neither measure was significant for the association between TB disease burden and MGIT. Overweight/obese individuals had an 8% decreased risk (RR=0.92, 95% CI, 0.79–1.19) of shorter time to result compared to those with normal BMI, after adjusting for confounders. The results of this study indicate that there is no significant association between BMI and MGIT in an adjusted model. However, there are several limitations to this result including, lack of cavitation data and failure to account for collinearity in the final model

Disordered T cell-B cell interactions in autoantibody-positive inflammatory arthritis

T peripheral helper (Tph) cells, identified in the synovium of adults with seropositive rheumatoid arthritis, drive B cell maturation and antibody production in non-lymphoid tissues. We sought to determine if similarly dysregulated T cell-B cell interactions underlie another form of inflammatory arthritis, juvenile oligoarthritis (oligo JIA). Clonally expanded Tph cells able to promote B cell antibody production preferentially accumulated in the synovial fluid (SF) of oligo JIA patients with antinuclear antibodies (ANA) compared to autoantibody-negative patients. Single-cell transcriptomics enabled further definition of the Tph gene signature in inflamed tissues and showed that Tph cells from ANA-positive patients upregulated genes associated with B cell help to a greater extent than patients without autoantibodies. T cells that co-expressed regulatory T and B cell-help factors were identified. The phenotype of these Tph-like Treg cells suggests an ability to restrain T cell-B cell interactions in tissues. Our findings support the central role of disordered T cell-help to B cells in autoantibody-positive arthritides

Effect of malnutrition on radiographic findings and mycobacterial burden in pulmonary tuberculosis.

BACKGROUND:The relationship between malnutrition and tuberculosis (TB) severity is understudied. We investigated the effect of malnutrition on radiographic findings and mycobacterial burden. METHODS:Subjects included newly diagnosed, smear-positive, culture-confirmed, pulmonary TB cases enrolled in the Regional Prospective Observational Research for TB (RePORT) cohort. Multivariate regression models were used to evaluate the relationship at start of treatment between body mass index (BMI) and chest radiograph (CXR) findings of cavitation and percentage of lung affected and mycobacterial growth indicator tube (MGIT) time to positive (TTP). Severe malnutrition was defined as BMI<16 kg/m2, moderate malnutrition as 16-18.4kg/m2, and "normal"/overweight as ≥18.5 kg/m2. RESULTS:Of 173 TB cases with chest x-ray data, 131 (76%) were male. The median age was 45 years (range 16-82); 42 (24%) had severe malnutrition and 58 (34%) moderate malnutrition. Median percentage of lung affected was 32% (range 0-95), and 132 (76%) had cavitation. Individuals with severe malnutrition had, on average, 11.1% [95% CI: 4.0-13.3] more lung affected, compared to those with normal BMI, controlling for diabetes and cavitation. In multivariable analyses, cases with severe malnutrition had a 4.6-fold [95% CI, 1.5-14.1] increased odds of cavitation compared to those with normal BMI, controlling for smoking. Median MGIT TTP was 194.5 hours. Neither severe (aRR 0.99; 95% CI, 0.9-1.2) nor moderate (aRR 0.97; 95% CI, 0.8-1.1) malnutrition was associated with MGIT TTP. CONCLUSION:We found that malnutrition was associated with increased extent of disease and cavitation on CXR. These findings may reflect the immunomodulatory effect of malnutrition on pulmonary pathology

A multidisciplinary assessment of pain in juvenile idiopathic arthritis

INTRODUCTION: Pain is prevalent in juvenile idiopathic arthritis (JIA). Unknowns regarding the biological drivers of pain complicate therapeutic targeting. We employed neuroimaging to define pain-related neurobiological features altered in JIA. METHODS: 16 male and female JIA patients (12.7 ± 2.8 years of age) on active treatment were enrolled, together with age- and sex-matched controls. Patients were assessed using physical examination, clinical questionnaires, musculoskeletal MRI, and structural neuroimaging. In addition, functional magnetic resonance imaging (fMRI) data were collected during the resting-state, hand-motor task performance, and cold stimulation of the hand and knee. RESULTS: Patients with and without pain and with and without inflammation (joint and systemic) were evaluated. Pain severity was associated with more physical stress and poorer cognitive function. Corrected for multiple comparisons, morphological analysis revealed decreased cortical thickness within the insula cortex and a negative correlation between caudate nucleus volume and pain severity. Functional neuroimaging findings suggested alteration within neurocircuitry structures regulating emotional pain processing (anterior insula) in addition to the default-mode and sensorimotor networks. CONCLUSIONS: Patients with JIA may exhibit changes in neurobiological circuits related to pain. These preliminary findings suggest mechanisms by which pain could potentially become dissociated from detectable joint pathology and persist independently of inflammation or treatment status

Proteomics based markers of clinical pain severity in juvenile idiopathic arthritis

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is a cluster of autoimmune rheumatic diseases occurring in children 16 years of age or less. While it is well-known that pain may be experienced during inflammatory and non-inflammatory states, much remains ambiguous regarding the molecular mechanisms that may drive JIA pain. Thus, in this pilot study, we explored the variability of the serum proteomes in relation to pain severity in a cohort of JIA patients. METHODS: Serum samples from 15 JIA patients (male and female, 12.7 ± 2.8 years of age) were assessed using liquid chromatography/mass spectrometry (LC/MS). Correlation analyses were performed to determine the relationships among protein levels and self-reported clinical pain severity. Additionally, how the expression of pain-associated proteins related to markers of inflammation (Erythrocyte Sedimentation Rate (ESR)) or morphological properties of the central nervous system (subcortical volume and cortical thickness) implicated in JIA were also evaluated. RESULTS: 306 proteins were identified in the JIA cohort of which 14 were significantly (p < 0.05) associated with clinical pain severity. Functional properties of the identified pain-associated proteins included but were not limited to humoral immunity (IGLV3.9), inflammatory response (PRG4) and angiogenesis (ANG). Associations among pain-associated proteins and ESR (IGHV3.9, PRG4, CST3, VWF, ALB), as well as caudate nucleus volume (BTD, AGT, IGHV3.74) and insular cortex thickness (BTD, LGALS3BP) were also observed. CONCLUSIONS: The current proteomic findings suggest both inflammatory- and non-inflammatory mediated mechanisms as potential factors associated with JIA pain. Validation of these preliminary observations using larger patient cohorts and a longitudinal study design may further point to novel serologic markers of pain in JIA. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12969-022-00662-1