P. D. Hinduja Hospital and Medical Research Centre

Low or abnormal plasma concentrations of anti-tuberculosis drugs can be a major reason for treatment failure or the emergence of drug resistance. Acetylator status, which affects drug metabolism, plays a key role in determining drug bioavailability. This study aimed to perform therapeutic drug monitoring (TDM) of rifampicin and isoniazid and to evaluate the correlation between plasma drug concentrations and acetylator status among Indian patients receiving first-line antituberculosis therapy. Plasma concentrations of rifampicin and isoniazid were measured using in-house standardized high-performance liquid chromatography methods, while acetylator status was determined by conventional PCR of NAT2 gene. Peak concentrations were estimated from 125 patients on first-line tuberculosis (TB) treatment. Among these, 56% exhibited subtherapeutic rifampicin concentrations and 28% had subtherapeutic isoniazid concentrations. Conversely, above normal (potentially toxic) concentrations were seen in 2% and 21% for rifampicin and isoniazid, respectively. Despite receiving the standard TB treatment regimen, only 62% of patients improved clinically, while 38% of patients continued harboring TB signs and symptoms, among which 6 patients (5%) developed rifampicin resistance during the treatment course. About 44% were slow acetylators, followed by 40% intermediate and 16% rapid acetylators. The acetylator status significantly influenced the plasma concentrations of both drugs. Slow acetylators had significantly higher isoniazid concentrations (p = 0.004) and lower rifampicin concentrations (p = 0.01) as compared to rapid acetylators. Abnormal concentrations of rifampicin and isoniazid are prevalent and a major concern. Acetylator status influences plasma concentrations of rifampicin and isoniazid. Hence, determining acetylator status and performing TDM could be instrumental in optimizing and improving TB outcomes.

Background:Heart failure (HF) remains a major public health challenge in India, with a need for effective and well-tolerated therapeutic strategies.Objective:The RESTORE-HF study evaluated the real-world effectiveness and safety of torsemide-spironolactone fixed-dose combination (FDC) in Indian patients with HF.Design:Prospective, multicenter, observational study.Methods:This study was conducted across 101 sites in India. Patients aged 18–75 years with HF with reduced ejection fraction and signs of congestion were enrolled and initiated on the torsemide-spironolactone FDC. Participants were followed over 3 weeks from baseline. The primary objective was the change in body weight. Secondary endpoints included changes in New York Heart Association (NYHA) functional class, edema, occurrence of adverse events (AEs), and physician and patient assessments of efficacy and tolerability.Results:Of the 1841 patients screened, 1752 were enrolled, and 1520 completed the study. The mean (SD) age of participants was 58.61 (9.45) years, of whom 61.05% were male. The study showed a significant reduction in mean body weight was observed from 75.54 kg at baseline to 73.13 kg at week 3 (mean difference: 2.41 kg; p < 0.0001). Additionally, an improvement in NYHA functional class and edema was observed over 3 weeks from baseline. Overall, 22.11% patients achieved no-edema stage. Only three mild AEs related to loose stools were reported, and no serious AEs or deaths occurred. Over 98% of physicians and patients rated the therapy favorably.Conclusion:The RESTORE-HF study demonstrated that the torsemide-spironolactone FDC may be associated with a mean body weight reduction of 2.41 kg and may be generally well-tolerated in Indian heart failure patients. Furthermore, the FDC may be linked to significant symptomatic improvement over 3 weeks in real-world clinical practice.

Ovarian cancer (OC) is a complex disease with challenges such as delayed diagnosis and development of chemoresistance. Exosomes play a crucial role in intercellular communication within the tumor microenvironment and have been reported to transmit drug-resistant traits and promote proliferation and metastasis. We aimed to investigate the role of exosomal miRNAs in OC, focusing on their involvement in chemoresistance, immune evasion, and metastasis. We investigated the expression levels of miR-182, miR-9, miR-130a, miR-20a, and miR-23b, which are implicated in chemoresistance, immune evasion, and metastasis in OC. We used real-time PCR to assess the expression of these miRNAs in different exosomal and non-exosomal fractions isolated from the serum of 20 chemo naive, 20 chemotreated, and 20 healthy women. Our results revealed that ovarian tumors release higher levels of EpCAM-positive exosomes, which carry specific miRNAs that reflect the tumor's influence on the exosomal cargo. Elevated levels of miR-182, and miR-9 were found in EpCAM-positive exosomes from OC patients, with miR-182 being associated with disease relapse and the FIGO stage. In addition, miR-20a was found to be elevated in exosomes from chemotherapy-treated OC patients, indicating chemotherapy's impact on the exosomal miRNA profile. Notably, the miRNA expression in EpCAM-negative exosomes remained unchanged, highlighting the selective loading of miRNAs in EpCAM-positive exosomes. Overall, the study highlights a probable mechanism for miRNA packaging and release in OC through EpCAM-positive exosomes, offering potential biomarkers for monitoring disease progression and relapse.

We report the case of a young male with gradually worsening knee pain and terminal restriction of flexion which on magnetic resonance imaging (MRI) showed features suggesting a diagnosis of synovial haemangioma in the posterior intercondylar region. The mass was excised, and the histopathology confirmed the diagnosis post-operatively. After excision, the patient was pain free with full range of movements at 2-year follow-up.

Anti-neurofascin (Nf) -associated neuropathies represent a distinct subset of immune neuropathies. While literature on this entity is evolving, there is currently no published data on these disorders from India. The study aims to characterize Indian patients presenting with anti-Nf-associated neuropathies. A retrospective chart review (January 2019-April 2024) of patients who had tested positive for one or more anti-Nf antibodies in a tertiary university teaching hospital was carried out. Their clinical, investigative, and therapeutic data were documented and analyzed. 38 patients with varied clinical presentations were studied. Acute and chronic forms were equally common. Sensorimotor weakness, sensory ataxia, tremors, and fluctuating course were common in the chronic group. Acute presentations were typically motor predominant, severe at onset, with rapid progression to nadir. Four patients with recurrent acute presentations were noted. A demyelinating predominant pattern was seen in 19, axonal predominant pattern in 16, and features of chronic immune radiculopathy in 3 patients. Nodal antibodies were more frequent than paranodal antibodies. About two-thirds of patients required more than two immunotherapeutic agents. A favorable response to rituximab was observed in 16/21 patients. Patients with both nodal and paranodal antibodies (Pan Nf neuropathies) were more severe and resistant to therapy. Anti-Nf-associated neuropathies in this Indian cohort were clinically heterogeneous, spanning acute, chronic, and recurrent phenotypes. Tremors, sensory ataxia, pain, and fulminant onset are valuable diagnostic clues. Pan-Nf-associated neuropathies were consistently severe and treatment-resistant. Rituximab demonstrated significant benefit in most cases, supporting its use in refractory and relapsing disease.

Introduction:The goal of femoral component positioning in cementless total hip arthroplasty (THA) is accurate restoration of joint biomechanics and a press fit between the implant and the endosteal surface of the proximal femur. We present a case detailing an intraoperative broach fracture during THA and introduce a minimally invasive technique for broach removal.Case Report:A 45-year-old male with left hip osteoarthritis underwent left THA, and the final broach fractured during the extraction attempt. Given the hole in the proximal part of the broach’s shoulder, we created a cortical window near the proximal femur to expose the defect. The successful extraction was accomplished using a Kuntscher nail extractor.Conclusion:Notably, this technique resulted in no morbidity and eliminated the necessity for extending the approach or additional soft-tissue dissection.Surgeons performing THA must be prepared for unexpected challenges and possess the necessary skills to address complications. This report presents a case of femoral broach fracture during THA and describes an effective, economical, and safe solution to resolve the issue.

Immunoglobulin G4-related disease (IgG4-RD) is a rare autoimmune fibroinflammatory condition that can affect multiple organs. Central nervous system (CNS) involvement is seen in only 2-4% of cases. Due to its rarity and heterogeneous presentation, it often mimics malignancies, infections, or other inflammatory conditions, leading to delayed diagnosis. We report two cases illustrating the spectrum of CNS IgG4-RD and highlight diagnostic and therapeutic considerations. Case 1: A 29-year-old male presented with new-onset generalized tonic-clonic seizures. Brain magnetic resonance imaging (MRI) revealed a left-sided, extra-axial dural-based enhancing lesion with vasogenic edema. Serum IgG4 was elevated (3.25 gm/dL), but whole body positron emission tomography-computed tomography (PET-CT) ruled out systemic involvement. Surgical resection of the lesion was performed. Histopathology revealed a lymphoplasmacytic infiltrate with fibrosis and an IgG4:IgG plasma cell ratio of 20%. The patient was treated with tapering corticosteroids and methotrexate, leading to complete radiological resolution and seizure control. Case 2: A 44-year-old woman with longstanding hypothyroidism presented with headache, tinnitus, polydipsia, and polyuria. Laboratory investigations revealed panhypopituitarism. Imaging revealed an enlarged pituitary with systemic fluorodeoxyglucose (FDG)-avid lesions on PET-CT. Serum IgG4 was elevated (3.01 gm/L). A diagnosis of probable IgG4-related hypophysitis with multisystem involvement was made. She was managed with pulse methylprednisolone followed by oral steroids, methotrexate, and desmopressin. Follow-up showed clinical and radiological improvement, and serum IgG4 levels normalized. These cases demonstrate the clinical heterogeneity of CNS IgG4-RD, ranging from isolated pachymeningitis mimicking neoplasia to multisystem hypophysitis with systemic uptake. While the 2020 diagnostic criteria emphasize an IgG4:IgG ratio ≥40%, case 1 underscores that lower ratios (e.g., 20%) may still be diagnostically relevant, particularly in meningeal disease. Both patients responded well to corticosteroids and methotrexate, supporting their role as effective first-line treatment. These cases add to the growing evidence base for CNS-specific IgG4-RD and emphasize the need for organ-specific diagnostic flexibility and long-term immunosuppressive strategies.