The aim of this study was to explore the utility of inflammatory biomarkers in the peripheral blood to predict response to treatment in extrapulmonary tuberculosis (EPTB). A Luminex xMAP-based multiplex immunoassay was used to measure 40 inflammatory biomarkers in un-stimulated plasma of 91 EPTB patients (48 lymphadenitis, and 43 pleuritis) before and at 2 and 6 months of treatment. Overall a significant change was observed in 28 inflammatory biomarkers with treatment in EPTB patients. However, MIG/CXCL9, IP-10/CXCL10, and CCL23 decreased in all patients' groups with successful treatment at both time points. At 2 months, 29/64 (45%) patients responded partially while 35/64 (55%) showed complete regress. Among good responders, a higher number of biomarkers (16/40) reduced significantly as compared to partial responders (1/40). Almost half (14/29) of partial responders required longer treatment than 6 months to achieve satisfactory response. The levels of MIG, IP-10, MIF, CCL22 and CCL23 reduced significantly among 80, 74, 60, 71, 51% good responders, as compared to 52, 52, 52, 59, 52% partial responders, respectively. A biosignature, defined by a significant decrease in any one of these five biomarkers, corresponded with satisfactory response to treatment in 97% patients at 2 month and 99% patients at 6 months of treatment. Change in inflammatory biomarkers correlates with treatment success. A five biomarker biosignature (MIG, IP-10, MIF, CCL22 and CCL23) could be used as an indicator of treatment success.

Individuals with newly diagnosed tuberculosis (TB) were screened for diabetes (DM) with fasting plasma glucose (FPG) in Pakistan. A significant decrease in FPG was observed when TB was treated. Of those with newly diagnosed DM, 46% and 62% no longer had hyperglycemia after 3 and 6 months, respectively. Individuals with known DM also showed a significant decrease in fasting plasma levels when treated for TB, but after 3 months none had normoglycemia, and after 6 months 9.2% were normoglycemic. Thus, TB-related DM may abate when the stress terminates, as is the case in gestational DM. However, because stress hyperglycemia may be associated with subsequent risk of developing DM, follow-up is recommended.

Extrapulmonary tuberculosis (EPTB) remains diagnostically challenging due to its paucibacillary nature and variable presentation. Xpert and culture are limited in EPTB diagnosis due to sampling challenges, low sensitivity, and long turnaround times. This study evaluated the performance of the MPT64 antigen detection test for diagnosing EPTB, particularly tuberculous lymphadenitis (TBLN) and tuberculous pleuritis (TBP), in a high-TB, low-HIV setting. Conducted at Gulab-Devi Hospital, Lahore, Pakistan, this study evaluated the MPT64 test’s performance against conventional diagnostic methods, including culture, histopathology, and the Xpert MTB/RIF assay. Lymph node biopsies were collected, and cell blocks were made from aspirated pleural fluid from patients clinically presumed to have EPTB. Of 338 patients, 318 (94%) were diagnosed with EPTB. For TBLN, MPT64 demonstrated higher sensitivity (84%) than Xpert (48%); for TBP, the sensitivity was 51% versus 7%, respectively. Among histopathology-confirmed TBLN cases, MPT64 outperformed both culture and Xpert (85% vs. 58% and 47%). Due to the low number of non-TB cases, specificity could not be reliably assessed. The MPT64 test shows promise as a rapid, sensitive diagnostic tool for EPTB, particularly TBLN, in routine settings. While sensitivity is notably superior to Xpert, further studies are needed to evaluate its specificity and broader diagnostic utility.

Background: The World Health Organization (WHO) recommends stool as an alternative respiratory sample (RS) for diagnosing pulmonary tuberculosis (PTB) in children <10 years. This study assessed stool-Xpert-Ultra diagnostic performance against microbiologically confirmed (MC-PTB) cases identified based on the composite reference standard (CRS) in children <15 years, stratified by age and nutritional status. Methods: Children <15 years with presumptive PTB were assessed at 2 tertiary-care hospitals in Pakistan. Stools and RS were tested using Xpert MTB/RIF-Ultra (Xpert-Ultra) and culture. Using the CRS, PTB cases were MC-PTB or clinically confirmed. Nutritional status was classified using WHO criteria. Stool-Xpert-Ultra diagnostic performance was assessed against MC-PTB or positive RS-Xpert-Ultra. Logistic regression identified predictors of microbiological yields. Results: Among 650 children, we obtained 587 RS, 258 stool and 195 both stool and RS. Of 650, 264 (41%) had MC and 136 (21%) had clinically confirmed PTB. Stool-Xpert-Ultra had sensitivity, specificity, and accuracy of 47%, 88%, 77%, and 72%, 73%, 72% against MC-PTB in children <10 and ≥10, respectively. Stool-Xpert-Ultra performed similarly against RS-Xpert-Ultra in each age group. Stool-Xpert-Ultra detected 11% additional MC-PTB cases when RS was negative or unavailable. Stool-Xpert-Ultra had high sensitivity (64%) in severely acute malnourished (SAM) children. Age ≥10, female, SAM and TB-consistent chest X-rays were strongly associated with stool and RS microbiological positivity. Conclusions: Stool-Xpert-Ultra demonstrated moderate sensitivity against MC-PTB in <10. It identified additional MC-PTB cases when RS was unavailable or/negative, making it a valuable noninvasive alternative, especially in children ≥10 and with SAM, where it missed fewer cases.

Background: This study aimed to identify factors influencing non-invasive ventilation (NIV) outcomes in patients with hypercapnic respiratory failure due to various respiratory conditions in a resource-limited intensive care unit (ICU) setting. These predictors can guide us in the prompt decision of ventilation, resulting in better outcomes. Methods: Patients requiring NIV for hypercapnic respiratory failure of any cause were included. Arterial blood gases were measured at 1 and 24 h, and an improvement in pH ≥ 7.35 was taken as a cut-off for early and late physiological responses, respectively. Binary regression analysis was used to identify predictors of physiological response, need for mechanical ventilation, and mortality. Results: Among 226 patients (139 males), the underlying causes were obstructive (71%), restrictive (25%), and infective disorders (4%). Older age, higher one-hour PCO₂, FiO_2, and respiratory rate were associated with increased mortality. Late physiological response correlated with higher IPAP and WBC counts, while higher WBC counts also predicted need for mechanical ventilation on binary logistic regression. Conclusions: Higher one-hour PCO₂, older age, higher FiO₂, respiratory rate, WBC count, and IPAP predicted an unfavorable outcome of NIV in acute hypercapnoic respiratory failure. Locally generated data can support timely escalation to mechanical ventilation and inform patient selection for initial NIV therapy in resource-limited settings.