Characteristics, predictors and consequences of tuberculosis treatment interruption: A multicentre retrospective cohort study.

OBJECTIVES: Treatment interruption is associated with poor tuberculosis (TB) treatment outcomes and increased drug resistance. To address the issue, we aimed to investigate the characteristics, predictors and consequences of treatment interruption. METHODS: We conducted a retrospective cohort study by retrieving 4 years (2018-2021) of TB patients' records at 10 public health clinics in Sarawak, Malaysia. Adult patients (≥18 years) with drug-susceptible TB were selected. Treatment interruption was defined as ≥2 weeks of cumulative interruption during treatment. The Chi-square test, Mann-Whitney U test, Kaplan-Meier and Cox proportional hazards regression were used to analyse the data, with p < 0.05 being considered statistically significant. RESULTS: Out of 2953 eligible patients, 475 (16.1%) experienced TB treatment interruption. Interruptions were most frequent during the intensive phase (46.9%, n = 223), with the greatest risk within the first 4 weeks of treatment. The median time to interruption was 2 weeks in the intensive phase and the cumulative interruption probability at the end of the intensive phase was 12.9%. Notably, treatment interruption occurred during both intensive and continuation phases for 144 patients (30.3%), while the remaining 108 (22.7%) experienced interruptions only during the continuation phase with a median time to interruption of 16 weeks. Three predictors were identified to increase the risk of treatment interruption: adverse drug reaction (aHR = 8.53, 95% Cl: 6.73-10.82), smoking (aHR = 2.67, 95% Cl: 2.03-3.53) and illicit drug use (aHR = 1.88, 95% Cl: 1.03-3.45). Conversely, underlying diabetes was associated with a reduced likelihood of treatment interruption (aHR = 0.72, 95% Cl: 0.58-0.90). Treatment interruption led to significant differences in treatment restarts (62.3% vs. 0.7%), changes in medications (47.8% vs. 4.9%), prolonged treatment duration (247 days [IQR = 105] vs. 194 days [IQR = 44.3]) and lower successful outcomes (86.5% vs. 99.9%). CONCLUSION: Understanding the temporal characteristics, predictors and negative consequences of treatment interruption can guide the development of time-relevant approaches to mitigate the problem.

Combination of 1.1 mm flexible cryoprobe with conventional guide sheath and therapeutic bronchoscope in biopsy of apical upper lobe solitary pulmonary nodule.

BACKGROUND: Lung cancer is frequently situated peripherally in the upper lobes of the lung. Acquiring adequate tissue from this difficult-to-reach area remains a challenge. Transbronchial cryobiopsy (TBCB) has the ability to acquire larger specimens, but the rigidity of the standard 1.9 mm and 2.4 mm cryoprobes frequently poses challenges when used with a guide sheath (GS). The novel 1.1 mm cryoprobe, being both smaller and more flexible, may address this limitation. We describe the usage of this 1.1 mm flexible cryoprobe with GS in the biopsy of solitary pulmonary nodules (SPN) in the apical segment of the upper lobe in two cases. CASE REPORT: Both procedures were conducted with advanced airway under total intravenous anaesthesia. 2.6 mm GS was used in combination with a 2.2 mm rEBUS probe, using a therapeutic bronchoscope. Case 1 describes a SPN in the apical segment of the right upper lobe that was inconclusive by forceps biopsy due to GS displacement and inadequate biopsy depth. A steerable GS combined with the novel cryoprobe subsequently overcame this issue. Case 2 describes a SPN in the apical segment of the left upper lobe in which the standard cryoprobe failed to advance through the GS due to steep angulation. It also highlights with shorter activation time, the novel cryoprobe enable biopsied tissue to be retrieved through the GS while the bronchoscope-GS remains wedgend in the airway segment. There were no bleeding or pneumothorax complications in both cases, and histopathological examination confirmed adenocarcinoma of the lung. CONCLUSION: The 1.1 mm flexible cryoprobe in combination with GS and therapeutic bronchoscope offers an option to acquire adequate tissue in difficult-to-reach regions in the lung such as the apical segment of upper lobes. Further prospective series to evaluate its performance and safety in SPN biopsy is highly anticipated.

Predictive factors for tuberculous peripheral pulmonary lesions during radial endobronchial ultrasound.

BACKGROUND: Tuberculosis frequently poses diagnostic challenge when it presents as a peripheral pulmonary lesion (TB-PPL). The growing use of radial endobronchial ultrasound (rEBUS) for PPL biopsy highlights the need to identify predictive factors for TB-PPL, which is crucial for procedure safety. METHODS: A six-year retrospective review at our institution on adult patients with TB and malignant-PPL diagnosed from rEBUS procedure from October 1, 2016, to December 31, 2022. Clinical, radiological, procedural, histological and microbiological data were extracted and analysed. RESULTS: 387 PPLs were included in our cohort, 32 % were TB-PPL and 68 % were malignant-PPL. The median age was 63 (IQR 55-70) years, with the TB-PPL group significantly younger. The median size of the target lesion was 2.90 (IQR 2.26-4.00) cm. The overall rEBUS diagnostic yield was 85.3 %, with a 1.3 % pneumothorax risk. Multivariate analysis identified independent predictors for TB-PPL, including age <60 years (adj OR 2.635), target lesion size <2 cm (adj OR 2.385), upper lobe location (adj OR 2.020), presence of a cavity on pre-procedural CT (adj OR 4.186), and presence of rEBUS bronchogram (adj OR 2.722). These variables achieved an area under the curve of 0.729 (95 % CI 0.673-0.795) with a diagnostic accuracy of 75.49 % (95 % CI 70.68-79.88). CONCLUSIONS: Despite non-specific radiological findings in TB-PPL, our study identifies younger age, target lesion size less than 2 cm, upper lobe location, the presence of cavitation, and rEBUS bronchogram were independent clinical predictors for TB-PPL. This prediction model potentially helps mitigate the risk of accidental TB exposure during bronchoscopic procedures. A future prospective cohort study to validate these findings is essential to allow proper triaging of patient planning for rEBUS procedure.

Exploring the optimal freeze time and passes of the ultrathin cryoprobe in transbronchial cryobiopsy of peripheral pulmonary lesions.

In PPL-TBLC, quality of tissue matters more than quantity for accurate diagnosis. Comparable diagnostic yield with 1.1-mm cryoprobe can potentially be achieved in 6 s of freezing and three or more passes. https://bit.ly/49cbmbW.

Development and validation of a predictive scoring model for risk stratification of tuberculosis treatment interruption.

BACKGROUND: Tuberculosis (TB) treatment interruption poses risks of antimicrobial resistance, potentially leading to treatment failure and mortality. Addressing the risk of early treatment interruption is crucial in tuberculosis care and management to improve treatment outcomes and curb disease transmission. OBJECTIVES: This study aimed to identify risk factors of TB treatment interruption and construct a predictive scoring model that enables objective risk stratification for better prediction of treatment interruption. METHODS: A multicentre retrospective cohort study was conducted at public health clinics in Sarawak, Malaysia over 11 months from March 2022 to January 2023, involving adult patients aged ≥18 years with drug-susceptible TB diagnosed between 2018 and 2021. Cumulative missed doses or discontinuation of TB medications for ≥2 weeks, either consecutive or non-consecutive, was considered as treatment interruption. The model was developed and internally validated using the split-sample method. Multiple logistic regression analysed 18 pre-defined variables to identify the predictors of TB treatment interruption. The Hosmer-Lemeshow test and area under the receiver operating characteristic curve (AUC) were employed to evaluate model performance. RESULTS: Of 2953 cases, two-thirds (1969) were assigned to the derivation cohort, and one-third (984) formed the validation cohort. Positive predictors included smoking, previously treated cases, and adverse drug reactions, while concurrent diabetes was protective. Based on the validation dataset, the model demonstrated good calibration (P = 0.143) with acceptable discriminative ability (AUC = 0.775). A cutoff score of 2.5 out of 11 achieved a sensitivity of 81 % and a specificity of 64.4 %. Risk stratification into low (0-2), medium (3-5), and high-risk (≥6) categories showed ascending interruption rates of 5.3 %, 18.1 %, and 41.3 %, respectively (P < 0.001). CONCLUSION: The predictive scoring model aids in risk assessment for TB treatment interruption, enabling focused monitoring and personalized intervention plans for higher-risk groups in the early treatment phase.

Feasibility of Cryobiopsy Specimen Retrieval Through Standard Guide Sheath for Peripheral Pulmonary Lesions Without Bronchoscope Removal.

BACKGROUND: Transbronchial cryobiopsy is a promising technique for biopsy of peripheral pulmonary lesions (PPL). However, cryobiopsy specimen retrieval can pose problems due to the risk of bleeding during the blind period when the bronchoscope and cryoprobe are removed en bloc. Artificial airways and prophylactic balloon placement are risk-reducing measures, but the latter is challenging in upper lobe PPL. Specimen retrieval through standard guide sheath (GS) system without the need for bronchoscope removal may now be feasible with the ultrathin cryoprobe. METHODS: Retrospective review of radial endobronchial ultrasound (rEBUS)-guided transbronchial cryobiopsy for PPL cases in which cryobiopsy specimen was retrieved through the GS over a 6-month period. RESULTS: Twenty patients were included with an overall median age of 66.50 (IQR: 53.0 to 76.7). The median procedural time was 30 (IQR: 25.0 to 33.7) minutes. Median target size was 3.20 (IQR: 2.17 to 4.84) cm with 85% of lesions demonstrated "within" rEBUS orientation. Overall technical feasibility was 85% with median cryoactivation of 4.0 (IQR: 3.0 to 4.0) seconds. No specimen was retrieved in 3 patients. The diagnostic yield for forceps and cryobiopsy was 70% and 60%, respectively, and the combined diagnostic yield was 85% (P<0.01 vs. forceps biopsy). Median aggregate size for forceps and cryobiopsy was 8.0 (IQR: 5.3 to 10.0) and 4.5 (IQR: 2.3 to 7.0) mm respectively (P<0.01). No pneumothorax was reported and mild self-limiting bleeding was encountered in 30% of cases. CONCLUSION: Retrieval of cryoprobe through standard GS appears to be a safe and feasible method that can simplify the transbronchial cryobiopsy procedure and complement forceps biopsy in specific cases.

An explorative analysis on the optimal cryo-passes and freezing time of the ultrathin cryoprobe in endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy.

EBUS-guided transbronchial mediastinal cryobiopsy (TBMC) has emerged as a promising biopsy tool for diagnosing hilar and mediastinal pathologies. However, several fundamental technical aspects of TBMC remain unexplored. This study aims to determine the optimal number of cryo-passes and freezing time of the ultrathin cryoprobe in EBUS-TBMC concerning specimen size and procedural diagnostic yield. We conducted a retrospective chart review of patients with mediastinal and hilar lesions who underwent EBUS-TBMC between January 2021 and April 2023 across three hospitals in Malaysia. A total of 129 EBUS-TBMC procedures were successfully completed, achieving an overall diagnostic yield of 88.4%. Conclusive TBMC procedures were associated with larger specimen sizes (7.0 vs. 5.0 mm, p < 0.01). Specimen size demonstrated a positive correlation with diagnostic yield (p < 0.01), plateauing at specimen size of 4.1-6.0 mm. A significant positive correlation was also observed between the number of cryo-passes and both specimen size (p < 0.01) and diagnostic yield (p < 0.05). Diagnostic yield plateaued after 2-3 cryo-passes. In contrast, longer freezing times trended towards smaller specimens and lower diagnostic yield, though not reaching statistical significance. The highest diagnostic yield was recorded at the 3.1-4.0 s freezing time. The safety profile of TBMC remains favourable, with one case (0.8%) of pneumothorax and nine cases (7%) of self-limiting bleeding. In our cohort, TBMC performance with 2-3 cryo-passes and a 3.1-4.0 s freezing time to achieve a total aggregate specimen size of 4.1-6.0 mm appeared optimal. Further prospective studies are needed to validate these findings.

A multiple comorbidities mouse lung infection model in ApoE­deficient mice.

Acute pneumonia is characterised by a period of intense inflammation. Inflammation is now considered to be a key step in atherosclerosis progression. In addition, pre-existing atherosclerotic inflammation is considered to play a role in pneumonia progression and risk. In the present study, a multiple comorbidities murine model was used to study respiratory and systemic inflammation that results from pneumonia in the setting of atherosclerosis. Firstly, a minimal infectious dose of Streptococcus pneumoniae (TIGR4 strain) to produce clinical pneumonia with a low mortality rate (20%) was established. C57Bl/6 ApoE -/- mice were fed a high-fat diet prior to administering intranasally 105 colony forming units of TIGR4 or phosphate-buffered saline (PBS). At days 2, 7 and 28 post inoculation (PI), the lungs of mice were imaged by magnetic resonance imaging (MRI) and positron emission tomography (PET). Mice were euthanised and investigated for changes in lung morphology and changes in systemic inflammation using ELISA, Luminex assay and real-time PCR. TIGR4-inoculated mice presented with varying degrees of lung infiltrate, pleural effusion and consolidation on MRI at all time points up to 28 days PI. Moreover, PET scans identified significantly higher FDG uptake in the lungs of TIGR4-inoculated mice up to 28 days PI. The majority (90%) TIGR4-inoculated mice developed pneumococcal-specific IgG antibody response at 28 days PI. Consistent with these observations, TIGR4-inoculated mice displayed significantly increased inflammatory gene expression [interleukin (IL)-1ß and IL-6] in the lungs and significantly increased levels of circulating inflammatory protein (CCL3) at 7 and 28 days PI respectively. The mouse model developed by the authors presents a discovery tool to understand the link between inflammation related to acute infection such as pneumonia and increased risk of cardiovascular disease observed in humans.

Peripheral transbronchial needle aspiration-guided pinpoint cryobiopsy of lung nodule without bronchus sign: A case report.

Peripheral transbronchial needle aspiration (pTBNA) allows the access of pulmonary nodules without bronchus sign but is limited to cytological examination. A 39-year-old man with left parotid carcinoma presented with an incidental lung nodule. Target localisation was performed with manual airway mapping, virtual bronchoscopic navigation, and pTBNA. Direct target validation using radial endobronchial ultrasound (rEBUS) was performed through the puncture defect. Targeted pinpoint biopsy with a 1.1 mm cryoprobe through the pTBNA puncture defect confirmed metastatic adenoid cystic carcinoma. Guided pTBNA with rEBUS validation followed by cryobiopsy of lung nodules without bronchus sign is potentially feasible for histological and molecular analyses.

Performance of radial endobronchial ultrasound for peripheral pulmonary lesions without automation technology in tuberculous endemic region: real-world experience in a single institution over 6 years.

Background: Peripheral pulmonary lesions (PPLs) in tuberculous endemic regions present a unique diagnostic challenge, as tuberculous PPL can mimic malignancy and potentially delay diagnosis for both conditions without a confirmatory investigation. While bronchoscopic biopsy using radial endobronchial ultrasound (rEBUS) guidance is becoming more common among pulmonologists, it is often performed with additional automation technology such as virtual bronchoscopic and electromagnetic navigation. This study aimed to evaluate the performance of rEBUS without such automation technology over a 6-year period in our institution. Methods: Retrospective chart review of all adult patients undergoing rEBUS-guided transbronchial biopsy for PPL in our institution over 6 years duration (October 2016 to December 2022). Results: A total of 551 PPLs were included with median target lesion size of 2.70 (interquartile range, 2.10-3.70) cm. In total, 84.2% of lesion demonstrated direct bronchus sign with 46.3% demonstrating concentric rEBUS orientation. The overall diagnostic yield was 78.8% [95% confidence interval (CI): 75.1-82.1%], with 1.1% rate of pneumothorax. Among the conclusive cases, 62.7% were malignant while 37.3% were tuberculous. Bronchus sign [adjusted odds ratio (adj. OR): 2.268] and concentric rEBUS orientation (adj. OR: 3.426) are independent predictors for conclusive procedure. The sensitivity of rEBUS for malignant and tuberculous disease was 85.27% (95% CI: 80.89-88.97%) and 71.77% (95% CI: 62.99-79.49%) respectively. A significant improving trend of diagnostic yield over time with reduction of median PPL size was observed with introduction of cryobiopsy and thin bronchoscopy into rEBUS service. Conclusions: rEBUS without automation technology remains relevant and useful in this era. rEBUS provides a rapid and safe diagnosis of PPL which may translate into better patient care.

Methacholine challenge test as an adjunctive investigative tool in patients with asthma-like symptoms: the Sabah experience.

INTRODUCTION: Patients with asthma-like symptoms pose a diagnostic dilemma when physical examination is normal. The usual practice in Malaysia would be to give empirical asthma treatment. Bronchial challenge test (BCT) is widely used in many countries to diagnose asthma objectively but it is not widely available in Malaysia. OBJECTIVE: To describe our experience with BCT using methacholine at Queen Elizabeth Hospital as a supporting tool in the investigation of patients with asthma-like symptoms. METHODOLOGY: Review of case notes of patients who underwent BCT from July 2008 till April 2009. BCT was performed via dosimeter technique. Results were classified as high hyper responsiveness if the provocative dose of methacholine required to achieve 20% fall in FEV1 (PD20) was less than or equal to 0.125 micromol, moderate hyper responsiveness if PD20 was between 0.125 to 1.99 micromol or mild hyper responsiveness if PD20 was between 2.00 to 6.6 micromol. PD20 of more than 6.6 micromol constitutes a negative MCT. RESULTS: 29 patients had BCT during the study period. 19 cases were included in this review. The age ranged from 13 to 70 years old. There were 12 males and 7 females. Duration of symptoms ranged from 2 weeks to 23 years. BCT was positive (mild or moderate hyper responsiveness) in 10 out of 19 patients. No patient had high bronchial hyper responsiveness. CONCLUSIONS: BCT is a useful adjunctive tool in the investigation of patients presenting with asthma-like symptoms. This test obviates empirical asthma treatment. BCT should be made available in all major hospitals in Malaysia.

Echographic septation: A potentially useful indicator discriminating tuberculous from malignant pleural effusion.

BACKGROUND: Tuberculous (TBE) and malignant (MPE) pleural effusions present with similar lymphocytic exudates. As TBE is an inflammatory and hypersensitivity process, we hypothesized that echographic septation may be more prevalent in TBE than in MPE, potentially serving as a good clinical predictor for TBE. METHODS: A total of 183 TBE and 266 MPE patients were recruited retrospectively. Multivariate logistic regression was performed to determine significant predictors for TBE. RESULTS: TBE diagnosis was confirmed histologically (caseating granuloma) in 84.7% of the cases, while MPE was biopsy-proven in 63.9% of the cases. Echographic septation was more evident in TBE than in MPE (46.5% vs. 8.2%, p < 0.001). Multivariate logistic regression analysis showed that male sex, serum leucocyte count ≤9 × 109/L or pleural fluid protein ≥50 g/L, and echographic septation (aOR: 9.28, p < 0.001) were independent predictors for TBE. These parameters collectively provided a diagnostic accuracy of 79.61% (95% CI 74.13-84.38). CONCLUSIONS: Echographic septation may potentially facilitate discrimination between TBE and MPE as part of a clinical prediction model. Prospective validation of this prediction model in an external cohort is anticipated.

A young lady with prolonged menstruation and a large lung mass.

Clinicians should maintain a high level of clinical suspicion for invasive aspergillosis in patients receiving immunosuppression, as early diagnosis and treatment are essential to prevent significant morbidity and mortality https://bit.ly/3qLG9Yx.

Point-of-care ultrasound in pre-bronchoscopy assessment of acute dyspnea: A case of concurrent massive pulmonary embolism and deep vein thrombosis.

Point-of-care ultrasound (POCUS) leads to efficient real-time diagnosis in a wide range of medical specialties. We describe the use of cardiac, lung and lower limb POCUS to rapidly diagnose massive pulmonary embolism and deep vein thrombosis in a 64-year-old patient presenting with acute dyspnea prior to elective bronchoscopy. Left femoral vein thrombus and features of increased right heart pressure on POCUS led to the decision to administer fibrinolytic therapy, with subsequent CT pulmonary angiogram confirming bilateral PE. The use of POCUS allowed for rapid imaging and interpretation leading to a rapid diagnosis of PE, thus fast-tracking lifesaving anticoagulation, especially in an outpatient setting.

¹8F-Fluoromethylcholine (FCH) PET imaging in patients with castration-resistant prostate cancer: prospective comparison with standard imaging.

PURPOSE: The aim of the study was to assess the utility of (18)F-fluorocholine (FCH), compared to standard imaging of bone scan (BS) and contrast-enhanced abdominopelvic computed tomography (CT), in patients with castration-resistant prostate carcinoma. METHODS: FCH has shown promise as a metabolic imaging agent for prostate carcinoma. Twenty-six patients with castration-resistant prostate carcinoma had FCH, BS and CT imaging within a 2-month period. Individual FCH-positive lesions in bone were compared to the BS and soft tissue lesions were compared to CT. The lesions were then classified as concordant or discordant for the presence or absence of prostate cancer metastases. Discordant bone or soft tissue lesions were followed up with BS or CT, respectively, at 6-month intervals for up to 2 years or until a definitive diagnosis of the discordant lesion could be made. RESULTS: In 13 (50%) of the patients, all lesions identified were concordant; this included 5 patients in whom no lesions could be identified with any imaging modality. In 21 patients, 183 lesions were observed with 149 being concordant and 34 (19%) being discordant (13 patients). Based on follow-up, FCH correctly identified the presence or absence of disease in 27 of 34 lesions, and in 14 cases FCH-positive lesions, not identified on initial imaging, were confirmed as disease on follow-up. The sensitivity, specificity, accuracy, positive predictive and negative predictive values for lesion detection by FCH are 96% (92-98%), 96% (81-99%), 96% (93-97%), 99% (96-100%) and 81% (64-88%), respectively, with 95% confidence intervals shown in parentheses. CONCLUSION: In this patient cohort, FCH shows good initial concordance (81%) with BS and CT in the detection of metastatic prostate carcinoma. Follow-up of the cases where FCH was initially discordant with subsequent BS or CT shows that FCH was accurate in determining the presence or absence of prostate metastasis in 79% of lesions. While FCH imaging as compared to BS and CT in this patient group has a good sensitivity and specificity for the detection of lesions representing prostate metastasis, further prospective studies are needed to determine its role.

Feasibility of manual bronchial branch reading technique in navigating conventional rEBUS bronchoscopy in the evaluation of peripheral pulmonary lesion.

BACKGROUND: Although radial endobronchial ultrasound (rEBUS) is an important verification tool in guided bronchoscopy, a navigational route was not provided. Manual airway mapping allows the bronchoscopist to translate the bronchial branching in computed tomography (CT) into a comparable bronchoscopic road map. We aimed to explore the feasibility of this technique in navigating conventional rEBUS bronchoscopy in the localisation of peripheral pulmonary lesion by determining navigation success and diagnostic yield. METHODS: Retrospective review of consecutive rEBUS bronchoscopy performed with a 6.2 mm conventional bronchoscope navigated via manual bronchial branch reading technique over 18 months. RESULTS: Ninety-eight target lesions were included. Median lesion size was 2.67 cm (IQR 2.22-3.38) with 96.9% demonstrating positive CT bronchus sign. Majority (86.7%) of lesions were situated in between the third and fifth airway generations. Procedure was performed with endotracheal intubation in 43.9% and fluoroscopy in 72.4%. 98.9% of lesions were successfully navigated and verified by rEBUS following the pre-planned airway road map. Bidirectional guiding device was employed in 29.6% of cases. Clinical diagnosis was secured in 88.8% of cases, majority of which were malignant disease. The discrepancy between navigation success and diagnostic yield was 10.1%. Target PPL located within five airway generations was associated with better diagnostic yield (95.1% vs. 58.8%, P < 0.001). There was 1 (1.0%) pneumothorax in our cohort. CONCLUSIONS: Manual bronchial branch reading technique in combination with conventional rEBUS is feasible in localisation of PPL, especially for lesions located within the first five airway generations.