Assessment of anti-PD-(L)1 for patients with coexisting malignant tumor and tuberculosis classified by active, latent, and obsolete stage

Background It is not a rare clinical scenario to have patients presenting with coexisting malignant tumor and tuberculosis. Whether it is feasible to conduct programmed death-(ligand) 1 [PD-(L)1] inhibitors to these patients, especially those with active tuberculosis treated with concurrent anti-tuberculosis, is still unknown. Methods This study enrolled patients with coexisting malignancy and tuberculosis and treated with anti-PD-(L)1 from Jan 2018 to July 2021 in 2 institutions. The progression-free survival (PFS), objective response rate (ORR), and safety of anti-PD-(L)1 therapy, as well as response to anti-tuberculosis treatment, were evaluated. Results A total of 98 patients were screened from this cohort study, with 45 (45.9%), 21 (21.4%), and 32 (32.7%) patients diagnosed with active, latent, and obsolete tuberculosis, respectively. The overall ORR was 36.0% for anti-PD-(L)1 therapy, with 34.2%, 35.5%, and 41.2% for each subgroup. Median PFS was 8.0 vs 6.0 vs 6.0 months (P=0.685) for each subgroup at the time of this analysis. For patients with active tuberculosis treated with concurrent anti-tuberculosis, median duration of anti-tuberculosis therapy was 10.0 (95% CI, 8.01–11.99) months. There were 83.3% (20/24) and 93.3% (42/45) patients showing sputum conversion and radiographic response, respectively, after anti-tuberculosis therapy, and two patients experienced tuberculosis relapse. Notably, none of the patients in latent and only one patient in obsolete subgroups showed tuberculosis induction or relapse after anti-PD-(L)1 therapy. Treatment-related adverse events (TRAEs) occurred in 33 patients (73.3%) when treated with concurrent anti-PD-(L)1 and anti-tuberculosis. Grade 3 or higher TRAEs were hematotoxicity (n = 5, 11.1%), and one patient suffered grade 3 pneumonitis leading to the discontinuation of immunotherapy. Conclusions This study demonstrated that patients with coexisting malignant tumor and tuberculosis benefited equally from anti-PD-(L)1 therapy, and anti-tuberculosis response was unimpaired for those with active tuberculosis. Notably, the combination of anti-PD-(L)1 and anti-tuberculosis therapy was well-tolerated without significant unexpected toxic effects.

Development of pulmonary tuberculosis in the patient with systemic sarcoidosis and brain involvement

The article presents a clinical case of pulmonary tuberculosis with destruction and bacterial excretion in the patient with systemic sarcoidosis and cerebral lesions. Tuberculosis was characterized by the infiltrate and cavity in S1+2 of the left lung, tuberculous mycobacteria were detected by microscopy, GeneXpertMBT/Rif, and culture. Systemic sarcoidosis with brain involvement was diagnosed based on intrathoracic lymphadenopathy in 2015, development of dissemination in the lungs and neurological symptoms by 2018, deterioration of changes by 2019, rapid partial resolution of foci in the lungs, and moderate regression of neurological disorders during the treatment with prednisolone. A full course of anti-tuberculosis chemotherapy (316 doses) resulted in persistent sputum conversion, resolution of the infiltrate and cavity healing. Prednisolone was administered simultaneously for 318 days with increased doses (45-35 mg) for the first 2 months, then titrated down to 15 mg and remained so until the end of the treatment with gradual reduction and discontinuation. Changes in the lungs and improvement of clinical and radiological manifestations of neurosarcoidosis were documented.

Factors Associated with Acid Fast Bacilli and Sputum Culture Conversion in Patients with Multidrug-Resistant Tuberculosis in Surabaya

Introduction: Indonesia is a high incidence country of multidrug-resistant tuberculosis. There are approximately 11,000 MDR TB cases, 2.8% of them are new cases and 16% of them are relapse cases. Although guidelines for MDR-TB are frequently designed, medication freely provided, and centers for treatment duly expanded, studies on time to sputum culture conversion have been very limited in Indonesia. Therefore the aim of the study is to identify risk factors that effect on sputum and culture conversion.Methods: Data on short-term regimen for MDR TB in Dr. Soetomo General Hospital from January 1st – December 31st, 2018 were collected with a total sampling approach, and fulfill the inclusion and exclusion. Data were analyzed by computer software IBM SPSS Statistic 24 for windows. Results: Male is more likely to have delayed sputum conversion and culture conversion but no statistical difference is observed (p>0.05). Smoking history is more likely to have delayed sputum and culture conversion but only in sputum smear test shows a significant difference (p≤ 0.05). Alcohol consumption has delay effect on sputum and culture conversion but there is statistically difference in only culture conversion (p<0.05). The high baseline smear test also affects delay the sputum and culture conversion but only in sputum smear reveals a significant effect (p<0.05).Conclusion: In this present study, we identified sex, smoking history, high bacillary loads as significant factors on sputum conversion. In addition, we revealed that alcohol-consumption history is a significant factor affecting on culture conversion.

Tuberculosis and Diabetes Mellitus Co-morbidity

: Tuberculosis (TB) and diabetes mellitus (DM) association poses the re-emerging problem nowadays and challenge on the way towards a tuberculosis-free world. There are some peculiarities in immune function of DM patients which make them more susceptible to infections, including TB. This results in higher prevalence of TB among DM patients (OR=1.15 according to the last meta-analysis). Clinical manifestations of DM/TB often differ from classical course of the disease – these patients are more frequently symptomatic, more inclined to cavitary disease and, according to some data, to lower lobe involvement. Data on multi-drug resistance prevalence among DM/TB patients are controversial and need further research, especially in terms of primary resistance. Higher frequency of adverse reactions, slower sputum conversion and foci regression make treatment in this population more difficult and worsen outcomes. Potential measures to lower the burden of co-morbidity are: new treatment regimens, bi-directional screening, proper DM managing and controlling, testing for latent tuberculosis infection and its treatment, and new vaccines development. Feasibility and efficacy of these measures are to be investigated in the context of settings with different DM and TB prevalence and available resources.

Socio-clinico-radiological profile of smear-positive pulmonary tuberculosis patients in association with sputum conversion and baseline hsCRP levels

Our was an observational follow-up study where the aim was to assess the baseline high-sensitivity C-reactive protein levels in 50 smear-positive pulmonary tuberculosis patients in association with socio-clinico-radiological profile and microbiological conversion. Smear and culture conversion of sputum samples at the end of intensive phase of anti-tubercular treatment were recorded. Baseline serum high-sensitivity C-reactive protein estimation was done by ELISA. Mean high-sensitivity C-reactive protein levels at baseline, smear/culture converted and delayed converters were 68.1 ± 22.2 mg/l, 66.7 ± 22.0 mg/l and 91.6 ± 6.7 mg/l, respectively; high-sensitivity C-reactive protein levels were significantly higher in delayed converters as compared to sputum converters. Significantly higher baseline high-sensitivity C-reactive protein levels were seen in patients with bilateral chest X-ray lesions, cavitations, evening rise of temperature, haemoptysis and dyspnoea as compared to those without these features. high-sensitivity C-reactive protein, being a non-specific inflammatory marker could be an adjunct tool for TB prognosis.

Determining the risk factors associated with delayed sputum conversion at the end of the intensive phase among tuberculosis patients

Background: In pulmonary tuberculosis (PTB), the sputum conversion rate at 2 months is frequently used to evaluate treatment outcomes and effectiveness of a TB control programme. Aims: The study aimed to estimate the rate of delayed sputum conversion and explore its predicting factors at the end of the intensive phase among smear-positive PTB (PTB +ve) patients. Methods: A 3-year retrospective study was conducted in the government hospital in Pulau Pinang from 2016 to 2018. During the study, a standardized, data collection form was used to collect data from the patient record. Patients aged over 18 years were recruited. Multivariable logistic regression analysis was used to identify significant independent variables associated with delayed sputum conversion. Results: A total 1128 of PTB patients were recorded visiting the TB clinic, 736 (65.2%) were diagnosed as PTB +ve; of these, 606 (82.3%) PTB +ve had a record of sputum conversion at the end of the intensive phase. Age ≥ 50 years, blue-collar jobs, smoking, heavy bacillary load, relapsed and treatment interrupted were significantly (P < 0.05) associated with delayed sputum conversion. Delayed sputum conversion rate at the end of the intensive phase was 30.5%. Conclusion: The rate of sputum smear conversion in the intensive phase of treatment was independently associated with high sputum smear grading at diagnosis, relapsed and treatment interrupted categories, old age and blue-collar occupations.

Respiratory Tuberculosis in Those over 70 Years of Age: Specific Course of the Disease and Diagnostic Difficulties

The objective: to study specific features of the course and diagnosis of respiratory tuberculosis in persons aged 70 years and older.Subjects and methods. Medical records of 93 patients aged 70 years and older who were hospitalized due to respiratory tuberculosis in 2000-2019 were retrospectively analyzed. Men made 60.2%, and women – 39.8%.Results. Often tuberculosis was detected late when referring for medical care (68.8%). In 59.4% of patients, tuberculosis was detected later than in 2 months after the onset of the first symptoms. 89.2% had multiple co-morbidities. Destruction was detected in 52.7% of patients, bacterial excretion – in 69.9%, and remaining post-tuberculosis changes – in 34.4%. Sputum conversion was achieved in 81.5% of patients and cavities were healed in 53.1%.

Effect of quitting smoking on health outcomes during treatment for tuberculosis: secondary analysis of the TB & Tobacco Trial

BackgroundDespite treatment, patients with tuberculosis (TB) who smoke have poorer outcomes compared with non-smokers. It is unknown, however, if quitting smoking during the 6 months of TB treatment improves TB outcomes.MethodsThe TB & Tobacco Trial was a double-blind, placebo-controlled randomised trial of cytisine for smoking cessation in 2472 patients with pulmonary TB in Bangladesh and Pakistan. In a secondary analysis, we investigated the hypothesis that smoking cessation improves health outcomes in patients during the TB treatment course. The outcomes included an eight-point TB clinical score, sputum conversion rates, chest X-ray grades, quality of life (EQ-5D-5L), TB cure plus treatment completion rates and relapse rates. These were compared between those who stopped smoking and those who did not, using regression analysis.ResultsWe analysed the data of 2273 (92%) trial participants. Overall, 25% (577/2273) of participants stopped smoking. Compared with non-quitters, those who quit had better TB cure plus treatment completion rates (91% vs 80%, p<0.001) and lower TB relapse rates (6% vs 14%, p<0.001). Among quitters, a higher sputum conversion rate at week 9 (91% vs 87%, p=0.036), lower mean TB clinical scores (−0.20 points, 95% CI −0.31 to −0.08, p=0.001) and slightly better quality of life (mean EQ-5D-5L 0.86 vs 0.85, p=0.015) at 6 months were also observed. These differences, except quality of life, remained statistically significant after adjusting for baseline values, trial arm and TB treatment adherence rates.ConclusionPatients with TB who stop smoking may have better outcomes than those who don’t. Health professionals should support patients in stopping smoking.

Effektivitas Suplementasi Vitamin D Dalam Mempercepat Konversi Sputum Pada Pasien Tuberkulosis

Latar Belakang: Tuberculosis merupakan penyakit infeksi oleh Mycobacterium tuberculosis. Tuberculosis merupakan salah satu diantara sepuluh penyebab utama kematian di dunia. Penelitian terdahulu membuktikan bahwa suplementasi vitamin D dapat meningkatkan aktivitas anti-mikrobial, mempercepat konversi sputum dan kultur, mengurangi inflamasi, meningkatkan clinical outcome, serta meningkatkan mediator untuk aktivitas anti-mikrobial. Meskipun demikian, masih terdapat perbedaan pendapat akan manfaat suplementasi vitamin D pada pasien tuberculosis paru.Tujuan: Mengevaluasi bukti yang ada sampai saat ini terkait manfaat suplementasi vitamin D terutama dalam mempercepat konversi sputum. Metode: Pencarian literatur dilakukan pada tiga databases terkemuka yakni PubMed, SCOPUS, dan Cochrane dengan kata kunci berupa “Tuberculosis”, “Vitamin D”, “Suplementation”, dan “Sputum Conversion” dengan seluruh kata yang berhubungan. Dari seleksi artikel berdasarkan kriteria inklusi dan eksklusif didapatkan 1 systematic review oleh Jollifee D et al (2019) dan 1 clinical trial oleh Afzal A et al (2018), yang kemudian ditelaah berdasarkan aspek validity, importance, dan applicability menggunakan form telaah dari Oxford Center for Evidence Based Medicine. Hasil: Kedua artikel memenuhi kriteria validity, importance, dan applicability masing-masing. Dari segi efikasi, penelitian Jollifee D et al membuktikan bahwa pemberian suplementasi vitamin D tidak mempercepat konversi kultur sputum pada populasi umum (aHR 1.06, 95% CI 0.91-1.23; P=0.44; P for heterogeneity=0.84), namun mempercepat konversi kultur sputum pada populasi MDR-TB(aHR 13.44, 95% CI 2.96-60.90). Kedua studi membuktikan bahwa pemberian suplementasi vitamin D mampu mempercepat konversi apusan sputum namun konversi apusan sputum memiliki validitas yang lebih rendah sebagai marker prognosis untuk outcome suatu tatalaksana dibandingkan konversi kultur sputum. Kesimpulan: Pemberian suplementasi vitamin D tidak mempercepat konversi kultur sputum namun mempercepat konversi apusan sputum. Diperlukan penelitian lebih lanjut terkait manfaat suplementasi vitamin D pada percepatan konversi kultur sputum populasi MDR-TB.

Metformin Role in Diabetic Patients with Tuberculosis: a Review

Tuberculosis (TB) epidemic is a global health challenge, and WHO estimated the incidence of the new cases reaching 11.1 million people in 2017. Indonesia is classified as a high TB burden country, with 8% of its population infected by TB and ranks third in the world. Type-2 diabetes mellitus (T2DM) is known comorbidity for TB patients. TB-T2DM patients have a higher chance of morbidity, mortality, relapse, bacterial resistance, treatment failure, and slower sputum conversion than TB patients without T2DM. Recent studies suggest that metformin may have a potential synergistic role for TB-T2DM patients. Metformin has immunomodulator properties that can improve the body's immune response and inflammatory response against TB in individuals with T2-DM.