Antituberculosis Chemotherapy Research Articles

Spinal tuberculosis - Current management approach

Broad narrative review. To review and summarise the current literature on the management of tuberculosis (TB) spine. A thorough review of literature was performed on the epidemiology, aetiology, pathophysiology, pathology, clinical features and management of TB spine. Spinal TB accounts for half of skeletal TB and remains a common cause of public health concern in the developing world. The thoracic spine segment is the most affected. Patient commonly present with back pain and gibbus. The diagnosis involves demonstrating Mycobacterium tuberculosis on microscopy or culture as well as characteristic histology findings. Magnetic resonance imaging is the gold standard imaging modality. Medical therapy with anti-TB agents is the mainstay of treatment. Surgery is supplementary and indicated in selected cases. Spinal TB carries a good prognosis when detected and treated early. Delays can be associated with the development of complications including difficult-to-manage deformities. Multi-drug anti TB chemotherapy remains the bedrock of treatment. Surgery is supplementary and when indicated, takes the form of abscess drainage, debridement and fusion with or without instrumentation.

КОМПЛЕКСНОЕ ИССЛЕДОВАНИЕ МОКРОТЫ ВПЕРВЫЕ ВЫЯВЛЕННЫХ БОЛЬНЫХ ТУБЕРКУЛЁЗОМ ЛЁГКИХ С ИСПОЛЬЗОВАНИЕМ ПОЛИМЕРАЗНОЙ ЦЕПНОЙ РЕАКЦИИ И МИКРОБИОЛОГИЧЕСКОГО КОНТРОЛЯ ЖИЗНЕСПОСОБНОСТИ МИКОБАКТЕРИЙ ТУБЕРКУЛЁЗА

Objective: The use of polymerase chain reaction (PCR) in a comprehensive study of sputum in newly diagnosed patients with pulmonary tuberculosis (PTB) in the control of mycobacterium tuberculosis (MTB) viability by the microbiological method. Methods: The object of the study – 59 newly diagnosed patients with PTB in admission for treatment and 28 patients with PTB two months after the start of anti-tuberculosis chemotherapy. The study material is the sputum of PTB patients. Identification of the dead and persistent MTB was noted with the positive result of PCR (PCR+) and the absence of growth of MTB on the dense of nutritional environment of Levenstein-Jensen. The DNASorb-B and Litekh sets were used for DNA extraction of Mycobacterium tuberculosis complex. For amplification, Politub and AmpliSens MBT kits were used. Detection of amplification products was carried out with electrophoresis in 1.7% agarose gel in the presence of bromide ethidium Results: Before treatment, PCR was detected in 52 (88.1%) of the 59 PTB patients examined, 34 (57.6%) tested positive for inoculation (culture+). 25 (42.4%) of patients, lack of growth of MTB out of 59 PTB patients. After 2 months of chemotherapy, PCR+ was detected in 23 (82.1%) out of 28 patients with PTB, culture+ – in 13 (46.4%), no growth of MTB was revealed in 15 (53.6%). Conclusion: Before treatment, PCR was detected in 52 (88.1%) of the 59 PTB patients examined, 34 (57.6%) tested positive for inoculation (culture+). 25 (42.4%) of patients, lack of growth of MTB out of 59 PTB patients. After 2 months of chemotherapy, PCR+ was detected in 23 (82.1%) out of 28 patients with PTB, culture+ – in 13 (46.4%), no growth of MTB was revealed in 15 (53.6%). Keywords: Pulmonary tuberculosis, polymerase chain reaction, microbiological method, mycobacterium tuberculosis viability, chemotherapy.

ХИРУРГИЧЕСКАЯ ТАКТИКА ПРИ ОЧАГОВЫХ ОБРАЗОВАНИЯХ ЛЕГКОГО В ПРОТИВОТУБЕРКУЛЕЗНОМ СТАЦИОНАРЕ

The objective of the study : to determine the efficacy of surgery for diagnosis of pulmonary nodules in patients of a TB hospital. Subjects and methods . 220 surgeries performed due to pulmonary nodules in 2015-2017 were analyzed, all surgeries were carried out in Primorsky Regional Clinical TB Dispensary of the city of Vladivostok. Results. To determine the etiology of pulmonary nodules, resection was performed in 89 (40.5%) patients, video-assisted thoracoscopic resection in 68 (30.9%), atypical resection in 43 (19.5%), and 20 (9.1 %) patients underwent extended resection of the lung. A histological test of surgical specimens confirmed pulmonary tuberculosis in 179/220 (81.4%; 95% CI 75.7-86.0%) patients. Microbiological tests detected multiple drug resistance in 39/179 (21.8%) cases; this fact was taken into account when prescribing subsequent anti-tuberculosis chemotherapy. Peripheral lung cancer was detected in 19/220 (8.6%; 95% CI 5.6-13.1%) patients, metastatic lesions – in 2/220 (0.9%), benign tumor (chondroma) – in 17/220 (7.7%), and lung cyst in 3/220 (1.4%). Thus, non-tuberculous etiology of pulmonary nodules was present in 41/220 (18.6%; 95% CI (14.1-24.3%) patients referred to TB hospital for diagnostic purposes.

ТУБЕРКУЛЕЗ КАК РЕЗУЛЬТАТ СИНДРОМА ВОССТАНОВЕНИЯ ИММУННОЙ СИСТЕМЫ ПОСЛЕ НАЧАЛА АНТИРЕТРОВИРУСНОЙ ТЕРАПИИ

Начало антиретровирусной терапии у ВИЧ-инфицированных лиц несет в себе высокий риск развития синдрома восстановления иммунной системы с проявлением ранее не диагностированных инфекций, в том числе туберкулеза.Целью исследования было оценить клинико-рентгенологические особенности и эффективность лечения туберкулеза, развившегося в результате СВИС после начала АРТ у ВИЧ-инфицированных пациентов. Материал и методы. Изучены 24 медицинские карты стационарных больных ко-инфекцией туберкулез/ВИЧ, находившихся на лечении в Республиканской клинической туберкулезной больнице г. Донецка, у которых туберкулез развился в течение первых трех месяцев после начала антиретровирусной терапии. На догоспитальном этапе всем пациентам перед началом противовирусного лечения проводили объективный осмотр, рентгенографию органов грудной клетки, определяли содержание CD4-лимоцитов крови. Результаты и обсуждение. Перед началом антиретровирусной терапии медианы содержания CD4 в крови пациентов составляли 35 кл/мкл и 4,7%, не имели жалоб 7 человек (29,2%)%, 13 (54,2%) отмечали повышение температуры тела, 12 (50,0%) – слабость, 8 (33,3%) – кашель с мокротой, 4 (16,7%) – снижение массы тела, и у 2 лиц (8,3%) имелась неврологическая симптоматика. Рентгенологически нормальная картина органов грудной клетки определялась у 11 больных (45,8%), у 13 (54,2%) имелось усиление легочного рисунка, у 6 (25,0%) – увеличение внутригрудных лимфатических узлов. Первые симптомы туберкулеза появлялись в сроки от 3 до 60 дней, медиана – 19 дней, все больные отмечали лихорадку и слабость, у 9 (37,5%) наблюдались признаки туберкулезного менингита, у 17 (70,8%) – генерализованного туберкулеза. За стационарный период лечения умерло 14 человек (58,3%). Из 9 больных туберкулезным менингитом погибло семеро (77,8%). Успешно закончили стационарный этап противотуберкулезной химиотерапии и были выписаны для продолжения лечения в амбулаторных условиях 8 человек (33,3%). Выводы. Туберкулез, развивающийся в результате синдрома восстановления иммунной системы, возникает у ВИЧ-инфицированных лиц с глубокой иммуносупрессией при назначении антиретровирусной терапии без антимикобактериальных препаратов, характеризуется быстрым развитием, склонностью к генерализации и неблагоприятным прогнозом. Особо злокачественным течением отличается туберкулезный менингит, при котором летальность достигает 77,8%. У 54,2% больных перед началом противовирусного лечения отмечались лихорадка, у такого же количества – усиление легочного рисунка, у 25,0% – увеличение внутригрудных лимфатических узлов. Наличие указанных симптомов является основанием для отсрочки антиретровирусной терапии и детального обследования пациентов. При невозможности верифицировать причину патологии целесообразно начинать противовирусное лечение под прикрытием противотуберкулезной химиотерапии, однако ее схема и продолжительность нуждаются в четкой регламентации.

Preliminary experience in treating thoracic spinal tuberculosis via a posterior modified transfacet debridement, instrumentation, and interbody fusion

BackgroundPosterior transfacet approach has been proved to be a safe and effective access to treat thoracic disc herniation. However, the therapeutic effect and safety of modified transfacet approach for treating thoracic spinal tuberculosis (TST) has not been reported in the clinical literature. In this study, the clinical efficacy and safety of a single-stage posterior modified transfacet debridement, posterior instrumentation, and interbody fusion for treating TST were retrospectively evaluated.Patients and methodsFrom 2009 to 2014, 37 patients with TST underwent a posterior modified transfacet debridement, interbody fusion following posterior instrumentation, under the cover of 18 months of antituberculosis chemotherapy. The patients were evaluated preoperatively and postoperatively in terms of Frankel Grade, visual analog scale (VAS) pain score, kyphotic Cobb angle, and bony fusion.ResultsThe follow-up time was 39.8 ± 5.1 months (29–50 months). No postoperative complication or recurrence of spinal tuberculosis was observed. Definitive bony fusion was achieved in all patients. At the final follow-up, 2 cases were rated as Frankel grade D, 35 as grade E. VAS was recovered from 8.4 ± 1.0 cm to 0.4 ± 0.8 cm. The kyphotic angles were corrected from 29.4 ± 10.9° to 17.6 ± 6.3°. Using the Kirkaldy-Willis criteria, functional outcome was excellent in 29 patients, good in 7, and fair in 1.ConclusionsOur preliminary results showed that single-stage posterior modified transfacet debridement, posterior instrumentation, and interbody fusion are effective and safe surgical options for treating TST.

Efficacy and safety of cryotherapy combined with balloon dilatation through electronic bronchoscope in the management of airway occlusion caused by scar stenosis type of tracheobronchial tuberculosis

Objective: To investigate the efficacy and safety of cryotherapy combined with balloon dilatation through electronic bronchoscope in the management of airway occlusion caused by scar stenosis type of tracheobronchial tuberculosis (TBTB). Methods: From December 2008 to May 2016, 98 cases of airway occlusion caused by scar stenosis of TBTB were diagnosed by microbiology, histopathology, CT (computer tomography), bronchial reconstructions and bronchoscopy. All patients underwent routine anti-tuberculosis chemotherapy and cryotherapy through bronchoscope. The patients whose airways were reopened successfully received balloon dilatation through bronchoscope subsequently. The treatment effects were estimated by indexes including clinical efficacy, modified medical research council (mMRC) dyspnea scale and complications. Results: Among the 98 patients, airway occlusion in 87 cases were reopened successfully by cryotherapy for (10±4) times, and then these patients received balloon dilatation through bronchoscope for (7±3) times subsequently. The total effective rates were 76.53% and 72.45% after 3 and 12 months after the treatments respectively. Analysis of the disease courses of patients with different therapeutic efficacy showed that the median disease course was 3 months in healed cases, 5 months in effective cases and 9 months in ineffective cases. There was a significant difference between the ineffective and the total effective cases in disease courses (t=-15.012, P<0.01). The average of mMRC score changed from (3.8±0.5) before the procedure, to (1.1±0.7), (1.2±0.7) and (1.2±0.7) immediately, 3 and 12 months after the treatments. The difference was significant between the scores before and after therapy (t=30.398-31.058, P<0.01), but not among the 3 scores after treatments. No serious complications were observed in all cases. Conclusions: Cryotherapy combined with balloon dilatation through electronic bronchoscope was a very safe and effective method in the management of airway occlusion caused by scar stenosis of tracheobronchial tuberculosis. A shorter course of disease indicated more benefits for patients.

Efficacy and safety of concurrent anti-Cancer and anti-tuberculosis chemotherapy in Cancer patients with active Mycobacterium tuberculosis: a retrospective study

BackgroundIn our previous study, colorectal cancer (CRC) patients with active Mycobacterium tuberculosis (MTB) tolerated concurrent anti-cancer chemotherapy (anti-CCT) and anti-MTB chemotherapy. In this study, we retrospectively confirmed the efficacy and safety of concurrent chemotherapy in a greater number of patients with different types of malignancies.MethodsWe enrolled 30 patients who were treated concurrently with anti-CCT and anti-MTB regimens between January 2006 and February 2016. Cancer and MTB treatments were administered according to the approved guidelines.ResultsPatient demographics included: men/woman: 24/6; median age: 66.5 years; Eastern Cooperative Oncology Group performance status 0–1/2/3–4: 24/4/2; Stage IIB–IIIC/IV/recurrence: 6/22/2; lung cancer (LC)/CRC/other: 15/10/5; and MTB diagnosis (before or during anti-CCT): 20/10 (LC: 8/7; CRC: 8/2; other: 4/1). For anti-CCT, 23 patients received two cytotoxic agents with or without targeted agents and 7 patients received a single cytotoxic or targeted agent. The overall response rate was 36.7%. Regarding anti-MTB chemotherapy, 22 patients received a daily drug combination containing isoniazid, rifampicin, and ethambutol, plus pyrazinamide in 15 of the 22 patients, followed by daily isoniazid and rifampicin; the remaining 8 patients received other combinations. Hematological adverse events of Grade ≥ 3 were observed in 19 (67.9%) of 28 patients; laboratory data were lost for the remaining 2. Grade 3 lymphopenia and higher were significantly more frequent in LC compared to other malignancies (P < 0.005). Non-hematological adverse events of Grade ≥ 3 were observed in 5 (16.7%) of 30 patients. One CRC patient experienced Grade 3 hemoptysis and another 2 experienced Grade 3 anaphylaxis. One patient with cholangiocellular carcinoma and gastric cancer experienced Grade 3 pseudomembranous colitis as a result of a Clostridium difficile infection. One patient (3.3%) died of pemetrexed-induced pneumonitis. The success of the anti-MTB chemotherapy was 70.0%. There were no MTB-related treatment failures. The median overall survival (months, 95.0% confidence interval) was 10.5 (8.7–36.7), 8.7 (4.7–10.0), 36.7 (minimum 2.2), and 14.4 (minimum 9.6) for all patients combined, LC, CRC, and Other malignancies, respectively. LC patients experienced delayed MTB diagnosis and shorter overall survival.ConclusionsConcurrent chemotherapy is effective and safe for treating cancer patients with active MTB.

Clinical-morphological characteristics of surgical treatment of multidrug-resistant pulmonary tuberculosis in the last 10 years

Objective — to analyze the surgical activity in cases of pulmonary MDR-TB taking into account laboratory parameters over a 10-years period (based on the materials of a highly specialized NIFP clinic).Materials and methods. A retrospective study of surgical activity for pulmonary tuberculosis, in particular multidrug-resistant was performed for a 10-years period. A total of 1.038 operations were carried out, 366 of them (35.3 %) with pulmonary MDR-TB. All cases of multidrug-resistance have been verified microbiologically. During the study period, the dynamics of the annual frequency of operations and their types in pulmonary MDR-TB was analyzed, and also the frequency of different types of operations depending on the clinical and morphological form of MDR-TB, morphological activity in various forms of lung lesions, taking into account histological findings. The results of a microbiological study of the resistance profile of mycobacteria were taken into account.Results and discussion. The annual total number of operations for pulmonary TB has been presented and among them — the percentage of MDR-TB cases over a 10-year follow-up period. It is shown that overall the surgical activity has slightly decreased, while the specific weight of operations at MDR-TB is quite stable. The change in the types of surgical interventions in cases of MDR-TB has been established over time, in particular, the reduction in the number of large operations such as pneumonectomy, which the authors associate with the improvement of both the regimens of anti-tuberculosis chemotherapy, and with the introduction of video-assisted minimally invasive surgical procedures into surgical practice. Dependence of the type of surgical intervention on the clinical-morphological form of pulmonary TB and the degree of morphological activity of a specific inflammatory process at the time of surgery was analyzed.Tuberculomas and fibro-cavernous TB are prevailed among operated patients with MDR-TB, and in most cases of these forms of pulmonary TB the activity of tuberculous inflammation remains, 83 and 97 % respectively, according to morphological features.It was established that the microbiological detection of multidrug-resistant strains of MBT in the NIFP clinic in cases of pulmonary MDR-TB with surgical treatment was effective only in a third of all cases.Conclusions. In the past 10 years, the trend of reducing the number of pneumonectomies and increasing the number of operations of a more radical nature has been observed in surgery of pulmonary MDR-TB. Surgical interventions are indicated mainly in fibro-cavernous TB and pulmonary tu­­berculomas. According to the results of the morphological study, at the time of the operation, the activity of a specific process is retained in more than 80 % of cases, which indicates the need for complex, including surgical, treatment of such patients.

Adjunctive dexamethasone for the treatment of HIV-infected adults with tuberculous meningitis (ACT HIV): Study protocol for a randomised controlled trial.

Background:Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Co-infection with HIV increases the risk of developing TBM, complicates treatment, and substantially worsens outcome. Whether corticosteroids confer a survival benefit in HIV-infected patients with TBM remains uncertain. Hepatitis is the most common drug-induced serious adverse event associated with anti-tuberculosis treatment, occurring in 20% of HIV-infected patients. The suggested concentration thresholds for stopping anti-tuberculosis drugs are not evidence-based. This study aims to determine whether dexamethasone is a safe and effective addition to the first 6-8 weeks of anti-tuberculosis treatment of TBM in patients with HIV, and investigate alternative management strategies in a subset of patients who develop drug induced liver injury (DILI) that will enable the safe continuation of rifampicin and isoniazid therapy. Methods:We will perform a parallel group, randomised (1:1), double blind, placebo-controlled multi-centre Phase III trial, comparing the effect of dexamethasone versus placebo on overall survival in HIV-infected patients with TBM, in addition to standard anti-tuberculosis and antiretroviral treatment. The trial will be set in two hospitals in Ho Chi Minh City, Vietnam, and two hospitals in Jakarta, Indonesia. The trial will enrol 520 HIV-infected adults. An ancillary study will perform a randomised comparison of three DILI management strategies with the aim of demonstrating which strategy results in the least interruption in rifampicin and isoniazid treatment. An identical ancillary study will also be performed in the linked randomised controlled trial of dexamethasone in HIV-uninfected adults with TBM stratified by LTA4H genotype (LAST ACT). Discussion:Whether corticosteroids confer a survival benefit in HIV-infected patients remains uncertain, and the current evidence base for using corticosteroids in this context is limited. Interruptions in anti-tuberculosis chemotherapy is a risk factor for death from TBM. Alternative management strategies in DILI may allow the safe continuation of rifampicin and isoniazid therapy.

EFFICIENCY AND SAFETY OF ROBOT-ASSISTED THORACOSCOPIC LOBECTOMIES WHEN MANAGING PULMONARYTUBERCULOSIS

Currently, there are no doubts about the relevance of surgery as a part of integral treatment. However, minimally invasive surgeries for treatment of pulmonary tuberculosis are rarely used due to post-inflammatory changes in the pleural space and lung root. And outcomes of robot-assisted lobectomies in pulmonary tuberculosis patients have never been investigated.The objective of the study: to investigate the efficiency and safety of robot-assisted surgeries in pulmonary tuberculosis patients.Subjects and methods.Since May 2013, 56 patients suffering from focal unilateral pulmonary tuberculosis were enrolled into a prospective study, after having an adequate course of anti-tuberculosis chemotherapy. At the moment of surgery, bacillary excretion persisted in 32% of patients, and 90.5% of patients had cavities.Results.All patients had robot-assisted lobectomies using the surgical system of Da Vinci Si. The average time of surgery made 174 minutes (90-380 minutes), the blood loss made 82 ml (10-500 ml). In 2 (3%) patients, a robot-assisted access was converted into lateral thoracotomy. The frequency of post-operative surgical complications made 25% [6].Conclusion.High clinical efficiency and safety are associated with robot-assisted lobectomies as a part of the integral treatment of pulmonary tuberculosis patients.

A bioactive implant in situ and long-term releases combined drugs for treatment of osteoarticular tuberculosis

Anti-tuberculosis chemotherapy with a long duration and adequate dosing is the mainstay for treatment of osteoarticular tuberculosis (TB). However, it is difficult for systemic administration to reach adequate local drug concentrations and achieve effective treatment. Herein, a hydroxyapatite (HA) scaffold implant combined with a drug-releasing system was designed to achieve in situ and long-term anti-TB drug release and highly efficient therapeutic activity in vitro and in vivo. The clinical anti-TB drugs hydrophilic isoniazid (INH) and hydrophobic rifampicin (RFP) were molecularly dispersed into polyvinyl alcohol (PVA) through immersion-curing techniques and were steadily adhered onto the surfaces of HA scaffolds (HA-drug@PVA). The HA-drug@PVA scaffolds showed a long-term, sustained drug release profile and killed proliferating Mycobacterium in vitro. In vivo experimental results revealed that the HA-drug@PVA scaffolds provided over 10- and 100-fold higher concentrations in muscles and bones, respectively, as well as a much lower concentration (<0.025) in blood. Furthermore, the HA-drug@PVA scaffold implanted in an osteoarticular TB rabbit model showed obvious bone regeneration and fusion due to the inhibition of TB-associated inflammatory changes. The excellent therapeutic effects indicate that in situ implant materials combined with a long-term drug release system are promising for the treatment of osteoarticular TB and other osteoarticular infections.

Cytokine profile and efficacy of chemotherapy depending on thyroid state in patients with pulmonary tuberculosis.

Objective of the study is definition of cytokine balance and the outcomes of chemotherapy of tuberculosis patients depending on their thyroid state. Materials and methods: 60 tuberculosis patients with pulmonary: 30 persons with unchanged thyroid gland and 30 persons with autoimmune thyroiditis and followed subclinical hypothyroidism were compared for the structure and the function of thyroid gland, cytokine balance and outcomes of antituberculosis chemotherapy. Thyroid glands of all patients were scanned by ultrasound. The levels of free thyroxine, thyroid stimulating hormone and antibodies to thyroglobulin and thyroid peroxidase in the serum were defined. At the same time the levels of tumor necrosis factor-α, interferon- γ and interleukins-2, -6, and -4 were measured. Outcomes of chemotherapy was estimated on the ground of general cri­terions: term and rate of stopping of bacilli excretion and healing of caverns in lungs. Results and discussion: In a com­parative analysis of the data obtained, it was found that in tuberculosis patients with autoimmune thyroiditis and subclinical hypothyroidism compared with tuberculosis patients without thyroid pathology free thyroxine values in average decrease, the level of thyroid-stimulating hormone increases and levels of antibodies to both thyroglobulin and especially to thyroid peroxidase increase. In patients with concomitant autoimmune thyroiditis with subclinical thy­roiditis, levels of pro-inflammation cytokines TNF-α, INF-γ, IL-2, IL-6 were significantly lower when compared with patients without thyroid pathology, and the level of anti-inflammation cytokine IL IL-4 was higher in a group of patients with autoimmune thyroiditis. Efficacy of chemotherapy was better in tuberculosis patients without thyroid pathology. These changes can be explained by a lower level of T4 in the systemic circulation of people with autoimmune thyroiditis and subclinical hypothyroidism. Conclusion: subclinical hypothyroidism accompanying concomitant autoimmune thyroiditis suppresses cytokine response in tuberculosis patients. That is followed worsening of treatment response during antituberculosis chemotherapy. Screening of thyroid state is recommended for TB patients for timely definition of thyroid pathology and its compensation if needed for improvement of the outcomes of antituberculosis chemotherapy.

Evaluation of isoprinosine to be repurposed as an adjunct anti-tuberculosis chemotherapy

Isoprinosine (Inos) or immunovir is a synthetic purine derivative with immune-modulatory and antiviral properties. The drug shows apparent in vivo enhancement of host immune responses by inducing pro-inflammatory cytokines and rapid proliferation of T-cell subsets. Strikingly, the cytokines induced by Inos also play crucial roles in providing immune resistance against Mycobacterium tuberculosis (Mtb). Inos has been licensed for several antiviral diseases; however, its efficacy against Mtb has not been tested yet. Since Mtb subverts the host immune system to survive within the host. Therefore, we hypothesized that the immune-stimulatory properties of Inos can be explored as an adjunct therapy for the management of tuberculosis. We have also outlined a systematic direction of study to evaluate if Inos could be repurposed for tuberculosis. The in vivo studies for therapeutic evaluation of Inos alone or in combination with the first line anti-TB drugs in a suitable TB disease model would provide a clearer picture of its utility as a host-directed anti-TB drug and may endow us with a new application of an existing drug to combat tuberculosis.

Adjunctive dexamethasone for the treatment of HIV-infected adults with tuberculous meningitis (ACT HIV): Study protocol for a randomised controlled trial

Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Co-infection with HIV increases the risk of developing TBM, complicates treatment, and substantially worsens outcome. Whether corticosteroids confer a survival benefit in HIV-infected patients with TBM remains uncertain. Hepatitis is the most common drug-induced serious adverse event associated with anti-tuberculosis treatment, occurring in 20% of HIV-infected patients. The suggested concentration thresholds for stopping anti-tuberculosis drugs are not evidence-based. This study aims to determine whether dexamethasone is a safe and effective addition to the first 6-8 weeks of anti-tuberculosis treatment of TBM in patients with HIV, and investigate alternative management strategies in a subset of patients who develop drug induced liver injury (DILI) that will enable the safe continuation of rifampicin and isoniazid therapy. Methods: We will perform a parallel group, randomised (1:1), double blind, placebo-controlled multi-centre Phase III trial, comparing the effect of dexamethasone versus placebo on overall survival in HIV-infected patients with TBM, in addition to standard anti-tuberculosis and antiretroviral treatment. The trial will be set in two hospitals in Ho Chi Minh City, Vietnam, and two hospitals in Jakarta, Indonesia. The trial will enrol 520 HIV-infected adults. An ancillary study will perform a randomised comparison of three DILI management strategies with the aim of demonstrating which strategy results in the least interruption in rifampicin and isoniazid treatment. An identical ancillary study will also be performed in the linked randomised controlled trial of dexamethasone in HIV-uninfected adults with TBM stratified by LTA4H genotype (LAST ACT). Discussion: Whether corticosteroids confer a survival benefit in HIV-infected patients remains uncertain, and the current evidence base for using corticosteroids in this context is limited. Interruptions in anti-tuberculosis chemotherapy is a risk factor for death from TBM. Alternative management strategies in DILI may allow the safe continuation of rifampicin and isoniazid therapy.

Adjunctive dexamethasone for the treatment of HIV-infected adults with tuberculous meningitis (ACT HIV): Study protocol for a randomised controlled trial

Background:Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Co-infection with HIV increases the risk of developing TBM, complicates treatment, and substantially worsens outcome. Whether corticosteroids confer a survival benefit in HIV-infected patients with TBM remains uncertain. Hepatitis is the most common drug-induced serious adverse event associated with anti-tuberculosis treatment, occurring in 20% of HIV-infected patients. The suggested concentration thresholds for stopping anti-tuberculosis drugs are not evidence-based. This study aims to determine whether dexamethasone is a safe and effective addition to the first 6-8 weeks of anti-tuberculosis treatment of TBM in patients with HIV, and investigate alternative management strategies in a subset of patients who develop drug induced liver injury (DILI) that will enable the safe continuation of rifampicin and isoniazid therapy. Methods:We will perform a parallel group, randomised (1:1), double blind, placebo-controlled multi-centre Phase III trial, comparing the effect of dexamethasone versus placebo on overall survival in HIV-infected patients with TBM, in addition to standard anti-tuberculosis and antiretroviral treatment. The trial will be set in two hospitals in Ho Chi Minh City, Vietnam, and two hospitals in Jakarta, Indonesia. The trial will enrol 520 HIV-infected adults. An ancillary study will perform a randomised comparison of three DILI management strategies with the aim of demonstrating which strategy results in the least interruption in rifampicin and isoniazid treatment. An identical ancillary study will also be performed in the linked randomised controlled trial of dexamethasone in HIV-uninfected adults with TBM stratified by LTA4H genotype (LAST ACT). Discussion:Whether corticosteroids confer a survival benefit in HIV-infected patients remains uncertain, and the current evidence base for using corticosteroids in this context is limited. Interruptions in anti-tuberculosis chemotherapy is a risk factor for death from TBM. Alternative management strategies in DILI may allow the safe continuation of rifampicin and isoniazid therapy.

Нефротуберкулез и мочекаменная болезнь

Urolithiasis and nephrotuberculosis, due to the similarity of the radiographic patterns, share the same differential diagnosis list. The study aimed to analyze the incidence of co-occurrence of nephrotuberculosis and urolithiasis and to determine the impact of urolithiasis on the clinical course of renal tuberculosis. This open cohort retrospective study comprised 843 patients with renal tuberculosis and 245 patients with urolithiasis. 1088 medical records were analyzed to identify cases with co-occurrence of these two diseases and determine the clinical presentation of renal tuberculosis, urolithiasis, and the comorbid state. Also, patients with pulmonary tuberculosis (44), urogenital tuberculosis (17), and chronic nonspecific pyelonephritis (12) were tested for serum concentration of total calcium and phosphorus. Of 843 patients with renal tuberculosis, 39 (4.6%), had concomitant nephrolithiasis. The combination of urolithiasis with nephrotuberculosis manifested by more severe symptoms; these patients had a more than two-fold risk of tuberculosis recurrence. Except for the incidence of renal colic and dysuria, the clinical manifestations of urolithiasis and nephrotuberculosis did not differ statistically significantly. Prolonged infectious and inflammatory process in the kidneys resulted in an increase in the excretion of oxalates, which was more pronounced in patients with nonspecific pyelonephritis (p<0.05). A three-month course of antituberculosis chemotherapy resulted in a 36.2% increase in the excretion of oxalates in patients with urotuberculosis (p<0.05). Excretion of uric acid also significantly increased after a three-month intake of antituberculosis drugs. In our study, the incidence of concomitant urolithiasis and urogenital tuberculosis was low (4.6%), but comorbidity significantly complicated the clinical course of the disease and worsened the prognosis of nephrotuberculosis. Antituberculosis polychemotherapy increases the risk for formation of urinary stones. Prevention of urolithiasis in patients with urogenital tuberculosis warrants further investigation.

The state of membranes of mononuclear leukocytes in patients with tuberculosis of lungs.

The sampling of examined patients comprised 308 individuals with medication sensitive (or with absence of data about resistance) tuberculosis of lungs without decay of pulmonary tissue with purpose to detect characteristics of alteration of content and structural organization of monocytic membranes before treatment and also against the background of application of chemotherapy according 1 standard regimen. The data of clinical radiologic examination of patients, bacterioscopy, molecular genetic analysis and analysis of phospholipid spectrum of membranes of mononuclears of peripheral blood were used. To detect particular classes of phospholipids the thin-layer flow chromatography was applied. The following fractions of phospholipids were detected: aggregated lysophospholipids, sphingomyelin, phosphatidylinositol, phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine. To evaluate structurally functional condition of mononuclears of peripheral blood under tuberculosis the coefficients of activity of phospholipase and membrane permeability were applied. It is established that in case of tuberculosis infection an alteration of functional activity and restructuring of membranes of mononuclears of peripheral blood is observed expressed by increasing of content percentage of phosphatidylinositol and phosphatidylethanolamine and in decreasing of level of sphingomyelin, phosphatidylcholine and phosphatidylserine. In patients with tuberculosis prior to treatment decreasing of coefficient of membrane permeability. After application of chemotherapy coefficient of membrane permeability returned to standard. The anti-tuberculosis chemotherapy gives rise to activation of phospholipase A2 that shows membrane destructive effect on mononuclears of peripheral blood and results in disorganization of their membranes manifesting in cumulation of lysophospholipids at simultaneous decreasing of percentage content of phosphatidylserine and phosphatidylcholine. The toxic effect of anti-tuberculosis chemotherapy has no effect on number of monocytes in peripheral blood. At that, disorganization of membrane structures of these cells and possible suppression of their functional activity occur.

Influence of phosphogliv® hepatoprotector on phospholipid spectrum of peripheral blood mononuclears in patients with tuberculosis of lungs.

The administration of the "Phosphogliv®" hepatoprotector in the comprehensive treatment of patients with pulmonary tuberculosis will allow determining its effect on the lipid composition of membranes of mononuclear cells under conditions of etiotropic chemotherapy according to 1 standard regimen. The determination of the ratios of the most important classes of phospholipids in membranes of peripheral blood mononuclear cells will give an idea of the structural-functional state violation of the most important representatives of the cellular immunity in patients with tuberculosis prior to treatment, against the backdrop of the intensive phase of the main course of chemotherapy as well as the change in these indices when the "Phosphogliv®" drug is administered in the comprehensive treatment therapy. The study included 356 patients with pulmonary tuberculosis of young and middle age, out of which 308 patients received etiotropic chemotherapy without the administration of phosphogliv, and 48 patients receiving comprehensive treatment used a combined scheme of oral-parenteral administration of phosphogliv. The administration of the "Phosphogliv®" hepatoprotector in the comprehensive treatment of tuberculosis patients made it possible to reduce the severity of the toxic effect of anti-tuberculosis drugs on peripheral blood mononuclear cells, to reduce the degree of disorganization of their membranes and to bring the phospholipid spectrum closer to the corresponding values of the control group. Direct positive clinical and radiological dynamics in 81.5% of patients in the second group and 87.5% in the third group was noted during the analysis of laboratory data and the X-ray pattern. After 2 months of the intensive phase of anti-tuberculosis chemotherapy, abacilation was achieved in 61% of patients having no phosphogliv administered, and in 81% of patients receiving complex therapy with the administration of "Phosphogliv®" hapatoprotector. More apparent positive X-ray dynamics (infiltration zone and dissemination foci decrease) was observed in patients receiving Phosphogliv®.

Breast tuberculosis: clinical spectrum, diagnostic dilemmas and management

Background: Tuberculosis breast is a less known form of extrapulmonary tuberculosis. It poses diagnostic difficulties and confused with breast carcinoma and pyogenic abscess. Objective of the study was to determine the varied presentations of breast tuberculosis, diagnostic difficulties and surgical treatments.Methods: Study was conducted in Department of Surgery at Shri Guru Ram Rai Institute of Health and Medical Sciences, Dehradun, Uttarakhand, India. 651 patients with breast diseases over two years from September 2015- August 2017 were seen at the institution out of which 31 clinically diagnosed patients of breast tuberculosis, confirmed by laboratory work-up, were included in this study. Information regarding demographic details, clinical presentation, cytology, histopathology and management was noted.Results: All patients were females with mean age of 32.5years and out of them 15(48.38%) patients were having breast abscess, 10(32.25%) presented with lump breast and 6(19.35%) with lump with multiple draining sinuses and scars. 27(87.1%) patients had primary breast tuberculosis. Histopathology and TB-PCR reliably helped in diagnosing the disease.Conclusions: The presentation of breast TB is variable, and diagnosis is usually delayed. It should always be kept in mind as differential diagnosis of breast lump and pyogenic abscess. The disease can be diagnosed through pathological tests and a high suspicion. The definite treatment is adequate anti-tuberculosis chemotherapy and surgical excision or drainage especially in recurrent abscesses.

Retroperitoneal laparoscopic nephroureterectomy with distal and intramural ureter resection for a tuberculous non - functional kidney.

ABSTRACTObjective:To evaluate the safety and feasibility of total retroperitoneal laparoscopic nephroureterectomy with urinary-bladder junction resection for a tuberculous nonfunctional kidney.Materials and Methods:A total of 27 individuals diagnosed with unilateral nonfunctional kidney secondary to tuberculosis were treated between June 2011 and June 2015. All patients had normal renal function on the contralateral side and underwent the standard four-drug anti-tuberculosis treatment for at least four weeks before surgery. Total retroperitoneal laparoscopic nephroureterectomy was performed in all patients, and the urinary-bladder junction of distal ureter was managed using different auto-suture techniques.Results:Nineteen male and 8 female patients with an average age of 47.3 years (range, 36-64 years) underwent surgery. All the operations were successfully performed without conversion. The median operative time was 109.3 min (range, 75-138 min), the median blood loss was 157.5 mL (range, 70-250 mL), and the median hospitalization time was 3.7 days (range, 3-6 days). No serious perioperative complications occurred. Anti-tuberculosis chemotherapy was prescribed to all patients, with the entire course of treatment lasting six months. No recurrence of tuberculosis of the bladder or the contralateral kidney was observed during the median follow-up period of 26.7 months (range, 6-54 months).Conclusion:Retroperitoneal laparoscopic nephroureterectomy with urinary-bladder junction resection is a safe and feasible approach for the treatment of tuberculous non-functional kidneys.