Anti-glomerular basement membrane (anti-GBM) glomerulonephritis is a rare cause of rapidly progressive glomerulonephritis in children. The disease is characterized by the formation of antibodies against the glomerular basement membrane, leading to diffuse glomerular injury and rapid deterioration of renal function if not diagnosed and treated promptly. We report the case of a 14 year-old girl who was admitted with acute-onset edema and hypertension. Initial investigations revealed hematuria, proteinuria, hypoalbuminemia, progressive renal impairment, and positive anti-GBM antibodies. Kidney biopsy confirmed the diagnosis, demonstrating diffuse crescentic glomerulonephritis with linear IgG deposition along the glomerular basement membrane. The patient was treated with high-dose corticosteroids, plasmapheresis, and mycophenolate mofetil. After three months of treatment, both clinical and laboratory parameters improved, with partial recovery of renal function. This case highlights the importance of early recognition and prompt treatment of pediatric anti-GBM disease and suggests that an MMF-containing combination regimen may be a feasible alternative to cyclophosphamide-based therapy in selected patients.

Mycobacterial-derived lipid-linked galactan (LLG) is an essential component of the Mycobacterial tuberculosis (Mtb) cell wall core arabinogalactan (AG), a well-established virulence factor and target of anti-tubercular drugs. Cross-membrane translocation of LLG is energetically unfavorable and is therefore catalyzed by WzmWzt, a prominent member of the polysaccharide ABC transporter sub-family. Here we present cryo-EM structures of WzmWztMtb to uncover critical steps of Mtb LLG translocation. Notably, densities suggestive of the mycobacterial-derived LLG substrates were observed in the structure of WzmWztMtb, indicating that the substrate may bind through two Wzm and two Wzt subunits. This proposed LLG binding is fulfilled by a fully upward extension of the Wzt gate helix, which serves as a critical step to prime Wzt for dimerization. The ATP-bound structure revealed a remarkable downward movement of the gate helix, together with the Wzt dimerization. The third, DDM/ATP-bound structure captured WztWzmMtb in an intermediate state with two DDM molecules in the Wzm central cavity. Using two conditional mycobacterial mutants for functional analyses, we have identified residues on the Wzm N-terminal interface helix (IFN) and on the Wzt helical domain are essential for LLG recognition and translocation in vivo. These data provide a clear structural basis for the development of Mtb cell wall targeted therapeutics for global tuberculosis treatment.

Tubercular uveitis (TBU) remains difficult to diagnose and monitor because microbiologic confirmation is uncommon and clinical phenotypes overlap with other inflammatory chorioretinal disorders. This narrative review integrates evidence from multimodal imaging, immune testing, systemic tuberculosis evaluation, molecular diagnostics, biomarkers, treatment response, and monitoring to support a practical probability-based approach to suspected TBU. A targeted search of PubMed, Embase, Web of Science, the Cochrane Library, and Google Scholar was conducted for English-language literature through May 10, 2026, prioritizing consensus statements, systematic reviews, multicenter studies, and clinically relevant imaging, biomarker, and treatment reports. Enhanced-depth and swept-source optical coherence tomography, optical coherence tomography angiography, fundus autofluorescence, indocyanine green angiography, and ultra-widefield fluorescein angiography provide complementary information on choroidal granulomas, serpiginous-like choroiditis, retinal vasculitis, ischemia, and paradoxical worsening. Tuberculin skin testing and interferon-gamma release assays support tuberculosis attribution but do not prove ocular causality, while polymerase chain reaction and emerging molecular assays increase specificity when positive. Cytokine profiles, type I interferon signatures, complement C1q, and cell-free DNA remain investigational. TBU should be managed as a clinicoradiologic and immunologic probability diagnosis that links phenotype, imaging, tuberculosis exposure evidence, mimic exclusion, antitubercular therapy decisions, anti-inflammatory timing, and longitudinal monitoring to reduce both missed TBU and unnecessary treatment.

Macozinone (MCZ, PBTZ169) is a potent clinical-stage benzothiazinone antitubercular agent that covalently inhibits the essential mycobacterial flavoenzyme DprE1. In some mammals, MCZ undergoes reductive dearomatization to H2MCZ, a Hydride Meisenheimer Complex, identified as the major circulating metabolite in humans. We demonstrate for the first time that the NADPH-dependent human prostaglandin reductases PTGR1 and PTGR2 catalyze MCZ dearomatization into H2MCZ, resulting in loss of antimycobacterial activity. This reaction represents a heretofore undescribed host-mediated metabolic inactivation pathway for a therapeutic agent. Although H2MCZ may constitute a transient reactive intermediate, ex vivo and cellular data indicate that it does not contribute to antimycobacterial activity in vivo. Pharmacological inhibition of PTGR1 and PTGR2 using diclofenac, indomethacin, dicumarol, or the selective inhibitor PTGR2-IN-1 suppresses H2MCZ formation and partially restores MCZ antimycobacterial activity in vitro. Together, these findings uncover a previously unrecognized noncanonical enzymatic mechanism of drug metabolism involving dearomatization in humans. Targeting prostaglandin reductases may represent a strategy to enhance benzothiazinone exposure and efficacy.

BACKGROUND Tuberculosis is a chronic granulomatous infection caused by Mycobacterium tuberculosis, which can affect multiple organs in the human body. Lupus vulgaris is the most common clinical type of cutaneous tuberculosis in China. It typically follows a chronic course, with skin lesions that are difficult to heal, making it prone to misdiagnosis and missed diagnosis. This report presents a case of chronic lupus vulgaris that remained untreated over an exceptionally long duration, demonstrating that lupus vulgaris can manifest as a chronic inflammatory focus. CASE REPORT This article reports a case of a 45-year-old woman with a rash on her right earlobe for more than 30 years without pain, with occasionally itching. The rash presents as a red, thickened plaque with yellow papules and pustules on the surface. She sought treatment at hospitals and completed a few examinations. The histopathology revealed multiple epithelioid cell clusters surrounded by dense lymphocytic and histiocytic infiltration in the dermis. The interferon gamma release assay was positive. The Xpert test was positive for Mycobacterium tuberculosis. Mycobacterial culture and acid-fast staining were positive, and the cultured organism was identified as Mycobacterium tuberculosis. The chest computed tomography showed a previous lesion in the right upper lobe. Based on these findings, the diagnosis was confirmed as lupus vulgaris on the right earlobe. After anti-tuberculosis therapy, the skin lesions improved significantly. CONCLUSIONS The case showed that patients with persistent skin lesions, nodules, or ulcers, particularly responding poorly to treatment, should undergo appropriate examinations to rule out cutaneous tuberculosis, including lupus vulgaris.

Post-tuberculosis lung disease (PTLD) is associated with persistent respiratory symptoms, reduced exercise capacity, impaired quality of life, and psychological morbidity despite successful completion of anti-tubercular therapy. Although pulmonary rehabilitation (PR) is an established therapeutic intervention, comparative evidence on home-based PR (HBPR) and hospital-based PR (HPR), particularly beyond 12 weeks, remains limited. So, to compare the effects of HBPR and HPR on clinical, functional, psychological, and pulmonary function outcomes in patients with PTLD, the study was done over a period of 24 weeks. This prospective comparative study included 50 patients with PTLD, of whom 30 underwent structured HBPR with weekly follow-up and 20 underwent supervised HPR. Allocation was based on feasibility and participant preference. Allocation was based on feasibility and participant preference. Participants were assessed at baseline, 12 weeks, and 24 weeks using the modified Medical Research Council (mMRC) dyspnea grade, body mass index (BMI), St. George's Respiratory Questionnaire (SGRQ), Depression Anxiety Stress Scale-21 (DASS-21), spirometry, and six-minute walk distance (6MWD). Changes within groups were analyzed for 0-12 weeks, 12-24 weeks, and 0-24 weeks, and change scores were compared between groups. Both rehabilitation strategies significantly improved dyspnea, nutritional status, quality of life, psychological well-being, pulmonary function, and exercise capacity over 24 weeks. In the HBPR group, mean 6MWD increased from 258.17±82.72 m to 377.00±82.38 m, while in the HPR group it increased from 308.00±118.84 m to 429.00±114.57 m (both p<0.001). Mean SGRQ scores improved from 44.67±9.28 to 29.73±7.00 in the HBPR group and from 38.70±10.35 to 25.10±8.30 in the HPR group (both p<0.001). Significant improvements were also observed in BMI, DASS-21 scores, forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), FEV₁/FVC ratio, and forced expiratory flow between 25% and 75% of vital capacity predicted values. Although the greatest gains occurred during the first 12 weeks, several outcomes continued to improve between 12 and 24 weeks. Change-score analysis demonstrated comparable improvements between HBPR and HPR across most outcomes. This study concluded that both home-based and HPR significantly improved clinical, functional, psychological, and pulmonary outcomes in PTLD. Benefits extended beyond 12 weeks, with comparable improvements observed between rehabilitation strategies.

Emergence of drug-resistant Mycobacterium tuberculosis necessitates the development of new drugs. Here, we studied the activity of new piperazine nitrofuranylamides against a collection of clinical strains from an multidrug-resistant tuberculosis (MDR-TB) high-burden country. A series of nitrofuranylamides 9-15 was synthesized and evaluated using a collection of diverse clinical strains representing globally spread genotypes (Beijing, LAM, and Haarlem; susceptible, MDR, and pre-extensively drug resistant). Minimal inhibitory concentrations (MIC) were determined using a resazurin assay. Whole-genome sequencing was performed on an Illumina HiSeq platform. Although clinical isolates differed in their MICs, some tested compounds-namely 11 and 12-showed higher MICs regardless of the clinical strain. In contrast, compounds 13-15 exhibited promising activity (MIC < 0.1 µg/mL) against the majority of strains. Moreover, 13 and 14 were previously shown to have low toxicity in JCL:ICR mice and low cytotoxicity against human cell lines. A closer look at structural variation indicated that the presence of a pyridine- or quinoline-type aryl substituent leads to a broader spectrum of activity. The additional nitro group in 14 appears to contribute significantly to its activity. A nonsynonymous mutation in the efflux pump gene Rv3728 (372 A > V, GCC → GTC) in one of the Haarlem genotype strains may speculatively correlate with its high-level intrinsic resistance to nitrofurans. Further biological research is warranted to investigate the mechanism of action of the most promising compounds.

A girl in the first decade of life presented with a 1.5 year history of gradually progressive bilateral upper eyelid swelling with bilateral proptosis, more prominent on the right side. She had a partial response to oral prednisolone, but symptoms recurred during tapering. Examination showed firm bilateral upper eyelid masses, preserved vision and mild restriction of upward gaze in the right eye. MRI demonstrated right preseptal/periorbital soft tissue thickening. Further evaluation excluded infection, vasculitis, sarcoidosis and malignancy; serum IgG4 level was normal. Biopsy of the right eyelid lesion showed concentric perivascular fibrosis with eosinophil-rich lymphoplasmacytic infiltrate, consistent with eosinophilic angiocentric fibrosis, supporting a diagnosis of possible organ-limited IgG4-related disease. The patient was treated with oral prednisolone and mycophenolate mofetil, resulting in sustained clinical improvement. This case highlights that paediatric IgG4-related disease may present as isolated orbital swelling with normal serum IgG4, making histopathology crucial for diagnosis.

Immune checkpoint inhibitor (ICI)-associated transverse myelitis (TM) is a rare and severe neurological immune-related adverse event (n-irAE) with an incidence of < 0.01%, and the clinical management of steroid-unresponsive cases remains extremely challenging. This article reports the case of a 37-year-old male patient with biphasic pleural mesothelioma who developed ICI-associated TM after treatment with nivolumab combined with ipilimumab. Initial treatment with high-dose glucocorticoids plus intravenous immunoglobulin (IVIg) was ineffective. After mycophenolate mofetil (MMF) was added in combination with steroids for 1 month, the patient's neurological function showed slight improvement, and intramedullary contrast-enhanced signals on spinal MRI showed partial reduction. However, spinal cord cystic or myelomalacic changes suggested potentially irreversible parenchymal injury. Currently, the patient has restarted pemetrexed combined with carboplatin chemotherapy, and the disease status is stable. Based on recently published case series, case reports, and systematic reviews, this article discusses the second-line treatment strategies for steroid-unresponsive ICI-associated TM, aiming to provide a reference for clinical practice in managing such rare cases.

Extrapulmonary tuberculosis (EPTB), including bone and joint involvement, was historically considered an extension of pulmonary disease and managed empirically with uniform treatment protocols. Over the past five decades, this perception has undergone a major transformation with EPTB now recognized as distinct clinical entity accounting for 15-25% of all TB cases, frequently affecting children, women, and immunocompromised individuals, often without pulmonary involvement, and contributing significantly to long-term morbidity. Spinal tuberculosis (STB) represents a unique form of EPTB characterized by a complex interplay of infection, biomechanics, and functional impairment. Unlike pulmonary TB, which is a multibacillary disease occurring in oxygen-rich lung tissue, STB is a paucibacillary disease arising in relatively hypoxic cancellous bone. Its pathology is driven largely by host immune response, leading to vertebral destruction, abscess formation, spinal instability, kyphotic deformity, and neurological deficits. Healing often occurs with fibrosis and bony fusion but may leave permanent structural and functional sequelae. The diagnostic paradigm has shifted from reliance on clinical suspicion and plain radiography to advanced imaging and tissue-based confirmation. MRI has emerged as the gold standard for early detection, assessment of disease extent, neural compression, and treatment monitoring. CT provides detailed evaluation of bony destruction and facilitates image-guided biopsy. Tissue diagnosis, combining histopathology, AFB smear/culture and microbiological techniques including CBNAAT and line probe assays, is now essential to ascertain etiology and detect drug resistance. This integrated diagnostic approach has significantly improved accuracy and enabled individualized management. Therapeutically, STB management has evolved from prolonged empirical regimens and immobilization to evidence-based, multidrug chemotherapy combined with selective surgical intervention. Standard treatment for drug-sensitive STB includes an intensive phase with isoniazid, rifampicin, pyrazinamide, and ethambutol, followed by a continuation phase tailored to disease severity, typically extending to 12 months. STB to be treated till healed status is demonstrated by contrast MRI/PET scan. Molecular diagnostics have facilitated early detection of drug resistance, enabling personalized second-line therapy in drug-resistant STB. Principles of treatment emphasize daily weight-based dosing, strict adherence, and uninterrupted therapy. Surgical management has transitioned from decompression alone to comprehensive strategies integrating decompression, stabilization, and deformity correction, with instrumentation now considered safe in infected bone. A major advancement has been the shift in treatment goals from mere infection control to a composite outcome encompassing clinical recovery, normalization of inflammatory markers, radiological healing, preservation of spinal stability, prevention of deformity, and restoration of function. Early diagnosis and risk stratification are critical, particularly in children, to prevent progressive kyphosis and long-term disability. In summary, STB has evolved from a disease associated with high mortality and disability to a condition with predictable healing and improved outcomes. Advances in imaging, molecular diagnostics, chemotherapy, and surgical techniques have transformed its management into a multidisciplinary, evidence-based approach focused on early diagnosis, individualized therapy, and functional restoration.