Lok Nayak Jai Prakash Narayan Hospital

Tuberculosis remains one of the world's deadliest infectious diseases. The pathophysiology of the two manifestations of Mycobacterium tuberculosis infection, pulmonary TB (PTB) and extrapulmonary TB (EPTB) is still not fully understood. Understanding the metabolic profile of both disease manifestations in patients is important for developing therapeutic approaches and molecular diagnosis. The current study aimed to elucidate differences in the gut metabolic profile of PTB and EPTB patients compared to healthy controls (HCs). We used an untargeted approach through 1H Nuclear Magnetic Resonance (NMR) spectroscopy to perform metabolomic profiling of stool samples from 77TB patients [pulmonary TB (PTB, n = 33), cervical lymph node TB (CrLNTB, n = 30), abdominal TB (ATB, n = 14)], and 30 HCs. Multivariate and univariate analyses were performed to identify the differential gut metabolites associated with TB patients. PTB patients showed greater metabolic perturbation than either EPTB group, with 24 metabolites significantly altered compared to 13 in ATB and 12 in CrLNTB, relative to HCs (adjusted p < 0.05). Each TB subtype displayed distinct metabolic profiles, yet several metabolites were commonly altered across all TB groups, including valine, N-formyl-L-methionine, choline, dimethylsulfone, tryptophan, valerate, N-acetylglutamate, creatine, and malonate. In the combined TB cohort versus controls, the most discriminatory metabolites were valine and N-formyl-L-methionine (AUC ≥ 0.80). Overall, these findings offer insights into the gut metabolome of TB patients in India and characterize for the first time metabolic perturbations in EPTB patients. The study highlights the metabolic disruptions associated with PTB and EPTB patients.

The aim of this study was to determine the prevalence of alloantibodies among transfusion-dependent thalassemia patients at our hospital. The present study is a retrospective study done at a tertiary care hospital in North India. All 92 patients with thalassemia, receiving blood transfusions during the study period were included in the study. The blood samples of these patients were collected immediately prior to transfusion. These samples were subjected to antibody screening by the indirect antiglobulin test utilizing a commercial three cell panel. Plasma samples that showed a positive result with antibody screening underwent antibody identification using an extended commercial eleven-cell panel. The secondary data were obtained from the records of these 92 patients. Four of the 92 patients developed alloantibodies. Among these four patients, one patient showed alloantibodies against E antigen, another against K antigen, while two patients had alloantibodies which did not show clear specificity using the eleven-cell panel. Alloantibodies were noted in two of the six patients having an Rh (D)-negative phenotype. A significant association was noted between Rh-negative blood group and alloimmunization (P = 0.0202). No significant association was observed between alloimmunization and patient age, age at first transfusion, pretransfusion hemoglobin, splenectomy status, serum ferritin level or annual red cell consumption. The prevalence (95% confidence interval) of alloantibodies in transfusion-dependent thalassemia patients in the present study was noted to be 4.3% (1.7%-10.6%). Patients with an Rh (D)-negative phenotype had a significantly higher prevalence of alloimmunization as compared to patients with an Rh (D)-positive phenotype.

Volume disturbances frequently occur after aneurysmal subarachnoid hemorrhage (a-SAH). Both hypovolemia and hypervolemia are associated with poor outcomes. Hence, we planned this study to determine preoperative volume status using echocardiography. The primary objective was to determine the incidence of preoperative hypovolemia in a-SAH patients with echocardiography. The secondary objectives include association between hypovolemia and induction hypotension and relative risk, and relative sensitivity and specificity of echocardiographic indices in predicting induction hypotension. Ninety-eight ASA-I or -II patients, aged 18-65 years, undergoing aneurysmal clipping surgery were included. Hypovolemia was assessed by inferior vena cava (IVC) diameter, IVC collapsibility index in subcostal view, left ventricular end-diastolic area and kissing-papillary sign in parasternal short axis view, and variations in left-ventricular outflow tract velocity-time integral (LVOT-VTI) in apical view. Induction-hypotension was defined as mean arterial pressure <70 mm of Hg until 10 min after induction. Out of 98 patients, 69 (70%) were hypovolemic and 59 (60%) developed induction hypotension with a relative risk of 2.26. The IVC-Cx and LVOT-VTI were the most sensitive parameters for determining induction hypotension (76% and 91%, respectively). A combination of IVC-Cx and kissing-papillary signs were most reliable for determining induction hypotension (P = 0.010). We conclude that the incidence of preoperative hypovolemia was 70%, and 60% of patients had induction hypotension. Dynamic parameters including IVC-Cx and VTI-variations are more reliable in predicting induction hypotension. We emphasize that preoperative screening of patients using ultrasound helps identify the hypovolemic patients in the preoperative area.

Hemophilia, an X-linked genetic bleeding disorder, is caused by the deficiency of coagulation factors VIII (hemophilia A) or IX (hemophilia B). Regular replacement therapy with the missing clotting factor is an effective standard-of-care treatment. However, it comes with a significant fallout of frequent intravenous dosing with poor compliance, the risk of inhibitor development, and a substantial treatment burden. Research has progressed from missing clotting factors and factor VIII mimetics to the most recent rebalancing therapy that suppresses tissue factor pathway inhibitor (TFPI). Thrombin generation is restricted by TFPI, which inhibits the tissue factor-mediated activation of factor VII. This promising therapeutic approach rebalances hemostasis by inhibiting TFPI, a critical regulator of the extrinsic coagulation pathway, thereby increasing thrombin generation. Novel monoclonal antibodies (concizumab and marstacimab) enhance thrombin generation by blocking TFPI to restore hemostasis. Clinical trials have demonstrated good clinical efficacy and safety of these anti-TFPI, besides their convenient subcutaneous administration using pen devices. These innovative therapies have the potential to enhance the quality of life (QoL) of people with hemophilia. This review provides a comprehensive overview of the clinical development, therapeutic potential, challenges, and prospects of anti-TFPI in the management of hemophilia.

Vulvovaginal enterobiasis is underreported and an often-missed diagnosis in prepubertal girls presenting with isolated nocturnal vulvar pruritus. An 8-year-old-girl with intense nocturnal vulvar itching for 4 months was diagnosed with enterobiasis after microscopy of a vaginal swab revealed Enterobius vermicularis (pinworm) ova. The child and her family were treated with two doses of oral albendazole, 2 weeks apart, resulting in symptom resolution. This case highlights the importance of considering enterobiasis as a differential diagnosis for nocturnal vulvar pruritus to prevent delayed treatment.