Metabolic switching and cell wall remodelling of Mycobacterium tuberculosis during bone tuberculosis

Bone tuberculosis is widely characterized by irreversible bone destruction caused by Mycobacterium tuberculosis . Mycobacterium has the ability to adapt to various environmental stresses by altering its transcriptome in order to establish infection in the host. Thus, it is of critical importance to understand the transcriptional profile of M. tuberculosis during infection in the bone environment compared to axenic cultures of exponentially growing M.tb. In the current study, we characterized the in vivo transcriptome of M. tuberculosis within abscesses or necrotic specimens obtained from patients with bone TB using whole genome microarrays in order to gain insight into the M. tuberculosis adaptive response within this host microenvironment. A total of 914 mycobacterial genes were found to be significantly over-expressed and 1688 were repressed (fold change>2; p-value ≤ 0.05) in human bone TB specimens. Overall, the mycobacteria displayed a hypometabolic state with significant (p ≤ 0.05) downregulation of major pathways involved in translational machinery, cellular and protein metabolism and response to hypoxia. However, significant enrichment (p ≤ 0.05) of amino-sugar metabolic processes, membrane glycolipid biosynthesis, amino acid biosynthesis (serine, glycine, arginine and cysteine) and accumulation of mycolyl-arabinogalactan-peptidoglycan complex suggests possible mycobacterial survival strategies within the bone lesions by strengthening its cell wall and cellular integrity. Data were also screened for M.tb virulence proteins using Virulent-Pred and VICM-Pred tools, which revealed five genes (Rv1046c, Rv1230c, DppD, PE_PGRS26 and PE_PGRS43) with a possible role in the pathogenesis of bone TB. Next, an osteoblast cell line model for bone TB was developed allowing for significant intracellular multiplication of M.tb. Interestingly, three virulence genes (Rv1046c, DppD and PE_PGRS26) identified from human bone TB microarray data were also found to be overexpressed by intracellular M. tuberculosis in osteoblast cell lines. Overall, these data demonstrate that M. tuberculosis alters its transcriptome as an adaptive strategy to survive in the host and establish infection in bone. Additionally, the in vitro osteoblast model we describe may facilitate our understanding of the pathogenesis of bone TB.

[18F]FDG Positron Emission Tomography for Initial Staging and Healing Assessment at the End of Therapy in Lymph Nodes and Bone Tuberculosis

Objective: In extra-pulmonary tuberculosis, therapeutic management is difficult in the absence of reliable tool to affirm healing at the end of treatment. In this prospective multicenter study, we evaluated [18F]FDG-PET for this purpose.Methods: Forty-two patients out of 55 included patients could be analyzed. Additionally to usual biological, histological and morphological explorations, [18F]FDG-PET was performed at diagnosis (PET1), at the end of treatment (PET2), indeed 6 months later. Then patients were followed until 12 months after end of prescribed treatment.Results: PET1 was positive in 97.6% of patients and discovered unknown injured sites in 52.7% of cases. PET2 was positive in 83.3% of uncured patients, and in 82.3% of cured patients. The sum and mean value of SUVmax measured in PET/CT lesions decreased between PET1 and PET2 in all patients. Mean value of SUVmax (MSUV) and sum value of SUVmax on PET2 showed the highest AUC on ROC curves for the diagnosis of healing at the end of prescribed treatment; MSUV 3.5 on PET2 had a sensitivity of 76.5% and a specificity of 80.0% to affirm healing at the end of prescribed treatment.Conclusions: [18F]FDG-PET/CT was useful at diagnosis, discovering unknown lesions in 52.7% of cases. MSUV on PET2 was the best criteria to affirm healing at the end of prescribed treatment.

Operative method of treatment of tuberculous spondylitis

After in the 90s of the XVIII century. the pathology of bone tuberculosis became known, it was found that the rest of the diseased joint is an essential factor in the fight against tuberculosis.

Tuberculous spondylitis

Tuberculous spondylitis in the Orthopedic Department of the Charit Surgical Polyclinic in Berlin, according to the study of Bergmann'a (Arch. F. Orthop. U. Unf-Chir., 1923, XXII), during the time from 1912 to 1922 was established 342 times, which is 23% in relation to all bone-tuberculosis patients.

On organizational forms of bone tuberculosis control in Tatarstan

We can note with great satisfaction the major achievements that our health organs have by this moment. Hundreds of new hospitals, many thousands of health centers, tens of thousands of nurseries and many different research institutions - these are the assets of Soviet health care. The question of the fight against tuberculosis also gained a lot of momentum. But we have one area which is not yet given full attention by the medical workers. This sphere is bone tuberculosis. A related and related to pulmonary tuberculosis disease, unfortunately, does not get the attention it deserves.

AB0780 GENDER FEATURES OF VERIFICATION OF DIAGNOSIS UNDIFFERENTIATED ARTHRITIS

Background:Undifferentiated arthritis (UDA) is an inflammatory arthritis that does not meet the criteria for any rheumatologic disease. Early verification of UDA is currently one of the main goals of modern rheumatology, since a diagnosis established at an early date allows determining a therapeutic strategy. The high social significance of arthritis lies in the predominant lesion of people of working age, the steady progression of the disease, early disability and a reduction in life expectancy.Objectives:To study the gender characteristics of verification of the diagnosis of undifferentiated arthritis.Methods:A retrospective analysis of 74 case histories of patients diagnosed with UDA was carried out. The study group consisted of 26 men and 48 women, mean age 50.6 ± 4.3 years. All patients underwent a comprehensive laboratory and instrumental examination according to the standard of an articular syndrome of unclear genesis.Results:According to the data obtained, the duration of the articular syndrome averaged 2.53 ± 1.2 years. In 29 patients (21.6% of women and 17.6% of men), on average, after 1.72 ± 0.9 years, the diagnosis of NDA was clarified. Taking into account modern diagnostic criteria, the following diseases were verified: rheumatoid arthritis in 13.5% (12.2% in women and 1.3% in men), ankylosing spondylitis in 10.8% (2.7% in women and 8.1% in men). Osteoarthritis, psoriatic arthritis and APS were diagnosed in 5.4%, 1.4% and 1.4% of women, and gouty arthritis, bone tuberculosis and HIV in 4.1%, 1.4% and 1.4% of men respectively. In 60.8% (43.2% in women and 17.6% in men), the etiology of arthritis was not verified.Conclusion:In a third of patients with UDA, diagnosis verification takes about 2 years on average. In more than half of patients, the diagnosis remains the same. According to the data obtained, rheumatoid arthritis was more often verified in women, while ankylosing spondylitis in men, which is consistent with statistical data.Disclosure of Interests:None declared