Aspek Patobiologis Pada Penyakit Trofoblas Gestasional

Penyakit trofoblas gestasional (PTG) mencakup mola hidatidosa (komplit dan parsial) dan tumor trofoblas gestasional (mola invasif, koriokarsinoma, placental site trophoblastic tumor, dan epithelioid trophoblastic tumour). Para ahli mempelajari kelainan perkembangan sel-sel trofoblas pada berbagai lesi trofoblastik PTG termasuk exaggerated placental site dan placental site nodule melalui gambaran morfologis, sitogenetik, imunofenotip, dan profil ekspresi gen. Upaya tersebut dilakukan untuk memahami patogenesis tumor trofoblas gestasional yang belum dipahami secara jelas, serta pengembangan diagnosis patologis dan molekuler dari berbagai tipe tumor trofoblas, pencarian petanda-petanda genetik untuk prognosis, dan penentuan target-target terapi potensial bagi bentuk metastatis dari PTG yang resisten terhadap pengobatan konvensional. Ketertarikan yang besar untuk mengetahui patogenesis PTG belumlah cukup bagi kemajuan penanganan PTG tanpa disertai ketekunan untuk mendapatkan petanda kanker yang tidak hanya diduga berperan dalam penyakit ini, namun dibutuhkan tahapan panjang dalam pencarian dan validasi petanda-petanda kanker untuk diagnostik, prognostik, dan target terapi

Improving Diagnostic of Pulmonary Tuberculosis in HIV Patients by Bronchoscopy: A Cross Sectional Study

Background: diagnostic of pulmonary TB in HIV patients is a problem due to non specific clinical features, or radiological appearance. HIV patients with CD4≤200 cells/mL infected with M. tuberculosis have less capacity in containing M. tuberculosis, developing granulomas, casseous necrosis, or cavities. This condition is caused by weakend inflammatory which later reduced sputum production and may cause false negative result. This study aimed to assess differences in the positivity level of acid fast bacilli (AFB) and cultures of M. tuberculosis from non-bronchoscopic sputum (spontaneous and induced sputum) compared to bronchoscopic sputum (bronchoalveolar lavage) in HIV positive patients suspected pulmonary tuberculosis with CD4<200 cells/μL.Methods: this cross sectional study was conducted in adult HIV patients treated in Hasan Sadikin Hospital with CD4≤200 cells/μL suspected with pulmonary tuberculosis by using paired comparative analytic test. All patients expelled sputum spontaneously or with sputum induction on the first day. On the next day, bronchoalveolar lavage (BAL) was performed. The two samples obtained from two methods were examined by AFB examination with staining Ziehl Neelsen (ZN) and cultured of M. tuberculosis on solid media Ogawa on all patients. Positivity, sensitivity and increased sensitivity of AFB and culture of M. tuberculosis in the non bronchoscopic and bronchoscopic groups were compared.Results: there were differences in the positivity level of AFB with ZN staining between non-bronchoscopic and bronchoscopic groups which were 7/40 (17.5%) vs 20/40 (50.0%) (p<0.001). The differences between the cultures of non-bronchoscopic and bronchoscopic groups were 16/40 (40.0%) vs 23/40 (57.5%) (p=0.039). Bronchoscopic sputum increased the positivity level of the ZN AFB examination by 32.5% (from 17.5% to 50.0%) as well as on culture examination by 17.5% (from 40.0% to 57.5%).Conclusion: Bronchoalveolar lavage can improve the positivity level of smears and cultures in patients suspected of pulmonary TB in HIV patients with CD4<200 cells/μL

Pharmacokinetics and safety/tolerability of isoniazid, rifampicin and pyrazinamide in children and adolescents treated for tuberculous meningitis

OBJECTIVE: To assess the pharmacokinetics and safety/tolerability of isoniazid, rifampicin and pyrazinamide in children and adolescents with tuberculous meningitis (TBM). DESIGN: Prospective observational pharmacokinetic study with an exploratory pharmacokinetic/pharmacodynamic analysis. SETTING: Hasan Sadikin Hospital, Bandung, Indonesia. PATIENTS: Individuals aged 0–18 years clinically diagnosed with TBM and receiving first-line anti-tuberculosis drug dosages according to revised WHO-recommended treatment guidelines. INTERVENTIONS: Plasma and cerebrospinal fluid (CSF) concentrations of isoniazid, rifampicin and pyrazinamide were assessed on days 2 and 10 of treatment. MAIN OUTCOME MEASURES: Plasma exposures during the daily dosing interval (AUC(0–24)), peak plasma concentrations (C (max)) and CSF concentrations. RESULTS: Among 20 eligible patients, geometric mean AUC(0–24) of isoniazid, rifampicin and pyrazinamide was 18.5, 66.9 and 315.5 hour∙mg/L on day 2; and 14.5, 71.8 and 328.4 hour∙mg/L on day 10, respectively. Large interindividual variabilities were observed in AUC(0–24) and C (max) of all drugs. All patients had suboptimal rifampicin AUC(0–24) for TBM treatment indication and very low rifampicin CSF concentrations. Four patients developed grade 2–3 drug-induced liver injury (DILI) within the first 4 weeks of treatment, in whom anti-tuberculosis drugs were temporarily stopped, and no DILI recurred after reintroduction of rifampicin and isoniazid. AUC(0–24) of isoniazid, rifampicin and pyrazinamide along with C (max) of isoniazid and pyrazinamide on day 10 were higher in patients who developed DILI than those without DILI (p<0.05). CONCLUSION: Higher rifampicin doses are strongly warranted in treatment of children and adolescents with TBM. The association between higher plasma concentrations of isoniazid, rifampicin and pyrazinamide and the development of DILI needs confirmatory studies

Treatment Outcomes of Childhood Tuberculous Meningitis in a Real-World Retrospective Cohort, Bandung, Indonesia

We retrospectively evaluated clinical features and outcomes in children treated for tuberculous meningitis (TBM) at Hasan Sadikin Hospital, Bandung, Indonesia, during 2011–2020. Among 283 patients, 153 (54.1%) were 38°C, stage III TBM, and baseline motor deficit. Despite treatment, childhood TBM in Indonesia causes substantial neurologic sequelae and death, highlighting the importance of improved early diagnosis, better tuberculosis prevention, and optimized TBM management strategies

Comparison between the Interferon γ Release Assay—QuantiFERON Gold Plus (QFT-Plus)—and Tuberculin Skin Test (TST) in the Detection of Tuberculosis Infection in Immunocompromised Children

Background. Immunocompromised patients are at a higher risk of having latent tuberculosis infection (LTBI). QuantiFERON-TB Gold Plus (QFT-Plus) has been proven to perform effectively in LTBI detection among immunocompromised adults and can overcome the limitations of the tuberculin skin test (TST). However, the role of QFT-Plus in detecting LTBI in immunocompromised paediatric patients has not been well established. Therefore, the aim of this study was to assess the test agreement between QFT-Plus and the TST in LTBI detection among immunocompromised children. Method. In this cross-sectional study, we enrolled immunocompromised paediatric patients, aged between 5 and 18 years, who were treated with corticosteroids and/or chemotherapy from June to November 2019. We categorized them into three groups based on the following diseases: hematologic malignancies and nephrological and immunological diseases. We recorded the patient characteristics and QFT-Plus and TST results, in which the positive result of the TST was induration≥5 mm. Within the same group, comparisons between the two tests were performed using the McNemar test, and results were statistically significant for p values of <0.05. The kappa index was used to assess the agreement between the two test results. Results. Among 71 patients (median age: 11.8 years) who underwent TST and QFT-Plus testing, 52% were females, and 69% had a normal nutritional status. Chemotherapy was the most common treatment modality for hematologic malignancy compared to other immunosuppressive treatments. The total number of patients with positive QFT-Plus and TST results was 11/71 (15.5%) and 4/71 (5.6%), respectively, among whom 3/11 patients had positive results in both tests, and one patient with positive TST results exhibited a discrepancy, as this was not followed by positive QFT-Plus results. QFT-Plus generated more positive results than the TST in immunocompromised children (McNemar, p=0.039 (p<0.05)). The diagnostic agreement between the tests was fair (K=0.345, 95% CI: 0.05–0.745). Conclusion. QFT-Plus detected LTBI more effectively than the TST in immunocompromised children

Comparison between the Interferon <i>γ</i> Release Assay—QuantiFERON Gold Plus (QFT-Plus)—and Tuberculin Skin Test (TST) in the Detection of Tuberculosis Infection in Immunocompromised Children

Background. Immunocompromised patients are at a higher risk of having latent tuberculosis infection (LTBI). QuantiFERON-TB Gold Plus (QFT-Plus) has been proven to perform effectively in LTBI detection among immunocompromised adults and can overcome the limitations of the tuberculin skin test (TST). However, the role of QFT-Plus in detecting LTBI in immunocompromised paediatric patients has not been well established. Therefore, the aim of this study was to assess the test agreement between QFT-Plus and the TST in LTBI detection among immunocompromised children. Method. In this cross-sectional study, we enrolled immunocompromised paediatric patients, aged between 5 and 18 years, who were treated with corticosteroids and/or chemotherapy from June to November 2019. We categorized them into three groups based on the following diseases: hematologic malignancies and nephrological and immunological diseases. We recorded the patient characteristics and QFT-Plus and TST results, in which the positive result of the TST was induration≥5 mm. Within the same group, comparisons between the two tests were performed using the McNemar test, and results were statistically significant for p values of &lt;0.05. The kappa index was used to assess the agreement between the two test results. Results. Among 71 patients (median age: 11.8 years) who underwent TST and QFT-Plus testing, 52% were females, and 69% had a normal nutritional status. Chemotherapy was the most common treatment modality for hematologic malignancy compared to other immunosuppressive treatments. The total number of patients with positive QFT-Plus and TST results was 11/71 (15.5%) and 4/71 (5.6%), respectively, among whom 3/11 patients had positive results in both tests, and one patient with positive TST results exhibited a discrepancy, as this was not followed by positive QFT-Plus results. QFT-Plus generated more positive results than the TST in immunocompromised children (McNemar, p=0.039 (p&lt;0.05)). The diagnostic agreement between the tests was fair (K=0.345, 95% CI: 0.05–0.745). Conclusion. QFT-Plus detected LTBI more effectively than the TST in immunocompromised children.</jats:p

Characteristics and surgical outcomes of tuberculous meningitis and of tuberculous spondylitis in pediatric patients at Dr. Hasan Sadikin Hospital, Bandung: A single center experience

Introduction: Tuberculous meningitis (TBM) and tuberculous spondylitis (TBS) are the form of extra-pulmonary tuberculosis. Material and method: A retrospective cohort study was conducted among children with TBM (2009–2014) and TBS (2004–2014) who were treated in our center; Department of Child Health, Department Neurosurgery and Department Orthopedics. Results: Of 123 children diagnosed with TBM (53) and TBS (70); based on modified British Medical Research Council: Stage I (3 cases), Stage IIa (3 cases), Stage IIb (23 cases), Stage III (24 cases). TBM developed hydrocephalus: 36 cases performed ventriculoperitoneal shunt and 17 cases external ventricular drainage. In TBM: 9.4% (5/53) had vegetative state and mortality rate was 20.8% (11/53). TBM Hospital discharge correlated with Glasgow coma scale preoperation (p<0.001). In TBS: Thoracic spine was involved in 67.1% cases, Lumbar in 28.6% and Cervical in 4.3%. Of 70 cases: 45 cases with neurological deficit and 25 cases without one. Of 24 cases underwent spine surgery: 6 cases performed anterior decompression spinal fusion and 18 cases performed posterior debridement with stabilization. In TBS patients, mortality rate was 1.4% (1/70). Conclusions: The surgical outcomes of both TBM and TBS still poor in many ways. Improving TB outcomes as implementation of the End TB Strategy program at 2030 remain our homework. Keywords: Surgical outcomes, Tuberculous meningitis, Tuberculous spondyliti