BACKGROUND: Cell subsets differentially modulate host immune responses to Mycobacterium tuberculosis (MTB) infection. However, the nature and functions of these subsets against osteoarticular tuberculosis (OTB) are unclear. Here, we aimed to understand the phenotypes and functions of immune cell subsets in patients with OTB using single-cell RNA sequencing (scRNA-Seq).
METHODS: Pathological and healthy adjacent tissues were isolated from patients with OTB and subjected to scRNA-Seq. Unsupervised clustering of cells was performed based on gene expression profiles, and uniform manifold approximation and projection was used for clustering visualization.
RESULTS: Thirteen cell subsets were identified in OTB tissues. scRNA-seq datasets of patients and healthy controls (HCs) showed that infection changed the frequency of immune cell subsets in OTB tissues. Myeloid cell examination revealed nine subsets. The frequency of macrophage-RGS1high subsets decreased in OTB tissues; this increased MTB susceptibility in an SLC7A11/ferroptosis-dependent manner. Immunohistochemistry assays and flow cytometry for patients with OTB and osteoarticular bacterial infection (OBI) and HCs verified that the frequency of macrophage-RGS1high subset decreased in OTB tissues and blood samples, thereby distinguishing patients with OTB from HCs and patients with OBI.
CONCLUSIONS: The macrophage-RGS1high subset levels were decreased in patients with OTB, and would be up-regulated after effective treatment. Therefore, the clinical significance of this study is to discover that macrophage-RGS1high subset may serve as a potential biomarker for OTB diagnosis and treatment efficacy monitoring.

UNASSIGNED: Tuberculosis (TB) is one of the most prevalent infectious diseases globally, often presenting with nonspecific symptoms that can obscure diagnosis, especially when it manifests in uncommon sites such as osteoarticular tuberculosis (OA-TB).
UNASSIGNED: We report a rare case of a 9-year-old male diagnosed with right knee tuberculosis after enduring severe symptoms for several months. Despite multiple negative biopsies and aspirates during initial debridement surgeries, a biopsy taken 6 months later confirmed the presence of Mycobacterium tuberculosis (MTB). The patient was subsequently treated with debridement and anti-tubercular therapy.
UNASSIGNED: This case underscores the critical need to consider tuberculosis in patients presenting with chronic bone pain to avoid misdiagnosis, particularly in the developing world. The atypical presentation of osteoarticular tuberculosis in this young patient emphasizes the need for healthcare professionals to recognize subtle symptoms. Advanced imaging studies like MRI and microbiological evaluations, including site biopsies, are essential for accurate diagnosis. Increased awareness and collaborative research are crucial to improving the understanding and management of pediatric osteoarticular tuberculosis and extrapulmonary tuberculosis.

UNASSIGNED: Osteoarticular tuberculosis (OATB) contributes to around 10% of extrapulmonary tuberculosis of which the spine is the most common site. Isolated involvement of ulna diaphysis is extremely rare. We present a case of unifocal tuberculous osteomyelitis of ulna diaphysis in a 3 -year-old male child and highlight its resemblance with musculoskeletal tumors and stress the importance of GeneXpert mycobacterium tuberculosis (MTB)/resistance to rifampicin (RIF) in the diagnosis of OATB.
UNASSIGNED: A mother of a 2-year-old male child incidentally noticed that her son complained of left forearm pain. She was not sure of any fall or trauma to the forearm. No history of fever or other constitutional symptoms was present. Clinical examination was uneventful except for local tenderness in over the dorsomedial aspect of the left mid forearm. A plain radiograph revealed an oval solitary lytic lesion over distal one-third ulna diaphysis. A needle biopsy was done after clinical, hematological, and radiological evaluation, and finally, GeneXpert detected tuberculosis without RIF. No further tests were required and the child was started on antitubercular therapy (ATT) which resulted in complete healing without any symptoms.
UNASSIGNED: The authors conclude that it is therefore essential to consider tuberculosis in the differential diagnosis while evaluating a lytic bone lesion. Where possible, all patients should have a biopsy of the lesion and provide a specimen for GeneXpert MTB/RIF to confirm the diagnosis and drug susceptibility testing.

We present a case report of a 66-year-old male patient with a known history of leprosy who presented with pain and swelling in his right foot for the past 1.5 years. Fine needle aspiration cytology (FNAC) revealed non-inflammatory exudate, and Mycobacterium tuberculosis (MTB) was identified in the sample by the cartridge-based nucleic acid amplification test (CBNAAT). The patient was managed conservatively with anti-Koch\'s treatment (AKT), and a follow-up was conducted for 12 months to monitor the treatment response and overall progress. This highlights the importance of early diagnosis and appropriate medical management, along with a long-term follow-up, among patients with ankle tuberculosis, to reduce the need for surgical intervention.

In this case report, a 29-year-old man underwent surgery to treat a fracture to the left distal end of his radius using closed reduction and K-wire fixation. The patient was advised to follow up in the outpatient department after six weeks for cast and K-wire removal. Still, the patient failed to do so and was doing alternate day dressing of the K-wires. After six months he slipped and fell from his cot while sleeping, sustaining an injury to the left wrist. Initially, he developed a swelling over the wrist, which suddenly increased in size and ruptured. Thick white caseous material was leaking out from the wounds. The patient underwent debridement and K-wire removal. An intraoperative sample was sent for a bacterial culture sensitivity test, histological analysis, and cartridge-based nucleic acid amplification test (CB-NAAT/GeneXpert). Postoperatively, anti-tuberculous treatment was started. The patient fully recovered from tuberculosis and had a complete range of movements after treatment.

This case report describes the unusual presentation of tuberculosis (TB) affecting the cuboid bone in a 16-year-old male patient. The patient presented with a one-year history of progressive foot pain, a discharging sinus, evening rise of temperature, weight loss, and loss of appetite. Clinical examination revealed soft tissue swelling and the presence of caseous material oozing from the sinus. Emergency debridement and curettage were performed, and bone cementing was carried out. An intraoperative sample was sent for a culture sensitivity test, histological analysis, and cartridge-based nucleic acid amplification test (CBNAAT). Histopathological examination, CBNAAT, and culture and sensitivity tests confirmed the diagnosis of Mycobacterium tuberculosis infection. Post-operatively, anti-tuberculous treatment was started. The patient fully recovered from TB of the cuboid.

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BACKGROUND: The present study was undertaken to determine the incidence of drug resistance against anti-tubercular drugs among patients from an endemic zone.  Methodology: Forty consecutive clinico-radiologically diagnosed patients of osteoarticular tuberculosis (29: spine, 11: extraspinal) were enrolled. Pus from needle aspiration was taken in 31 cases, tissue following spinal decompression in seven, synovial in one, and sinus edge biopsy in one. The pus/tissue was subjected to acid-fast bacilli (AFB) staining and liquid culture, sensitivity to 13 anti-tubercular drugs (Isoniazid (INH), rifampicin (RIF), kanamycin (KAN), amikacin (AMK,) capreomycin (CAP), ethionamide (ETH), levofloxacin (LEV), moxifloxacin (MOX), linezolid (LNZ), para-amino-salicylic acid (PAS), bedaquiline (BDQ), delamanid (DLM), and clofazimine (CFO)) were checked, and histopathological/cytopathological examination and molecular tests were performed.   Results: The mean age of patients was 29.07(9-65) years; 21 were female and 19 were male. The diagnostic accuracy for tuberculosis was 20% by AFB smear, 65% by liquid culture, 82.5% by histopathology, and 90% by cartridge-based nucleic acid amplification testing (CBNAAT). All culture-positive isolates were identified as Mycobacterium tuberculosis with no non-tubercular Mycobacterium. The drug resistance detected on CBNAAT was 11.1%, line probe assay (LPA) first line was 15.4%, LPA second line was 4%, and liquid drug susceptibility testing (DST) 11.5%. We detected 15.4% INH resistance, 11.1% RIF, 7.6% LEV, 3.8% MOX and PAS. No resistance was detected against second-line injectable drugs (SLID), ETH, LNZ, BDQ, DLM, and CFO.    Conclusions: No single laboratory modality can ascertain the diagnosis in all cases; hence, samples should be sent for all tests in tandem. In the presence of insufficient samples, tissue may be subjected to CBNAAT and histopathology to arrive at tissue diagnosis. In this subset, overall drug resistance incidence was 12.5% (5/40) with one patient each of isolated INH and RIF resistance, one of multidrug-resistance (MDR), and two of pre-extensively drug-resistant (pre-XDR). Primary drug resistance came out to be 11.1% (4/36) with one patient each of isolated INH and RIF resistance, one of MDR, and one Pre-XDR.

Background: Since the poor response to existing anti-tuberculosis drugs and low drug concentration in local bone tissues, the traditional drug therapy does not result in satisfactory treatment of osteoarticular tuberculosis. Thus, we report a rifapentine release system with imparted bone targeting potential using tetracycline (TC) -modified nanoparticles (NPs). Methods: TC was conjugated to PLGA-PEG copolymer via a DCC/NHS technique. Rifapentine-loaded NPs were prepared by premix membrane emulsification technique. The resulting NPs were characterized in terms of physicochemical characterization, hemolytic study, cytotoxicity, bone mineral binding ability, in vitro drug release, stability test and antitubercular activity. The pharmacokinetic and biodistribution studies were also performed in mice. Results: Rifapentine loaded TC-PLGA-PEG NPs were proved to be 48.8 nm in size with encapsulation efficiency and drug loading of 83.3% ± 5.5% and 8.1% ± 0.4%, respectively. The release of rifapentine from NPs could be maintained for more than 60 h. Most (68.0%) TC-PLGA-PEG NPs could bind to HAp powder in vitro. The cellular studies revealed that NPs were safe for intravenous administration. In vivo evaluations also revealed that the drug concentration of bone tissue in TC-PLGA-PEG group was significantly higher than that in other groups at all time (p < 0.05). Both NPs could improve pharmacokinetic parameters without evident organ toxicity. The minimal inhibitory concentration of NPs was 0.094 μg/mL, whereas this of free rifapentine was 0.25 μg/mL. Conclusion: Rifapentine loaded TC-PLGA-PEG NPs could increase the amount of rifapentine in bone tissue, prolong drug release in systemic circulation, enhance anti-tuberculosis activity, and thereby reducing dose and frequency of drug therapy for osteoarticular tuberculosis.

UNASSIGNED: Tuberculosis of the Temporomandibular joint (TMJ) in a neonate is a rare entity. Undiagnosed/mismanaged tuberculosis can disseminate and be life-threatening to the patient. The purpose is to present a case of tubercular osteomyelitis of TMJ in a neonate with eleven years of follow-up.
UNASSIGNED: A one-and-a-half-month-old male neonate presented with a firm swelling in front of the left ear for the past 20 days. Ultrasound presented an avascular, hypoechoic lesion of 34*25*25mm. Irregular margins of underlying bone could suggest erosion. Aspiration revealed pus. ZN staining of pus revealed Mycobacterium tuberculosis. After draining the pus, the patient underwent antitubercular therapy. He revisited at ten years of age with a complaint of asymmetry. Although the patient got cured of his tuberculosis, investigations rose to a diagnosis of condylar hypoplasia with ipsilateral coronoid enlargement. A distraction of the mandible improved facial symmetry.
UNASSIGNED: Although pus revealed the presence of Acid-fast bacilli, it is not evident until there is a significant bacterial load. Escalation of tests with higher sensitivity is needed to diagnose tubercular osteomyelitis of TMJ. Patients must be made aware of possible sequelae of tubercular osteomyelitis of TMJ and need appropriate management. Oblique osteotomy at the angle and distraction improves both horizontal and vertical components of the mandible and thus improves symmetry. To the best of the author\'s knowledge, the following is the first case of primary tuberculosis of TMJ in a neonate and with such an extended follow-up.