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.

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.

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.

Images of the month: Pulmonary cement embolism.

Percutaneous vertebroplasty (PV) involves injection of polymethylmethacrylate bone cement into vertebral body for relief of pain and strengthening of bone in symptomatic vertebral compression fractures.Passage of bone cement into vertebral venous plexus and then into the lungs is a rare and serious complication of PV. The reported incidence up to 26%.We present an incidental finding of pulmonary cement embolism (PCE) after PV. A 68-year-old woman with history of PV 3 years previously for T11 osteoporotic fracture presented to us with cough for 3 weeks following choking on a fish bone.Chest X-ray showed left lower zone consolidation and a high-density opacity in a tubular branching pattern, corresponding to pulmonary arterial distribution. Contrasted computed tomography of the thorax showed segmental pulmonary cement embolism of both lungs and left lower lobe consolidation.She underwent bronchoscopy with findings of a purulent secretion from the left lower lobe. Her symptoms resolved after 2 weeks of antibiotics. She was managed conservatively for the PCE as she remained asymptomatic.This case highlights the need for a standard post-PV chest X-ray, as patients with cement embolisms can be completely asymptomatic. Measures to minimise the risk of pulmonary cement embolisms during PV need to be taken.

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.

Pleural fluid lactate as a point-of-care adjunct diagnostic aid to distinguish tuberculous and complicated parapneumonic pleural effusions during initial thoracentesis: Potential use in a tuberculosis endemic setting.

BACKGROUND: Tuberculous pleural effusions (TBEs) and parapneumonic pleural effusion (PPEs) have similar clinical presentations and fluid biochemistry. A pleural biopsy is usually required to diagnose TBE but complete fluid evacuation may not be necessary, contrasting with complicated PPE (CPPE). A point-of-care test that distinguishes between TBE and CPPE enables the appropriate procedures to be performed during the initial diagnostic thoracentesis. Lactate is a metabolic product measurable by a blood-gas analyzer. This study measured pleural fluid (Pf) lactate levels in TBE and compared them with those in PPE/CPPE. We hypothesized that Pf lactate would be significantly higher in PPE because of active metabolic activities than in TBE which is driven by delayed hypersensitivity. METHODS: All patients undergoing an initial diagnostic thoracentesis over 18 months with Pf lactate measured using a calibrated point-of-care blood gas analyzer were assessed. RESULTS: The diagnoses of the enrolled patients (n = 170) included TBE (n = 49), PPE (n = 47), malignancy (n = 63), and transudate (n = 11). Pf lactate level in TBE, median 3.70 (inter-quartile range 2.65-4.90) mmol/l, was significantly lower than in PPE and CPPE. In the subgroup of TBE and CPPE patients whose initial Pf pH and glucose could suggest either condition, Pf lactate was significantly higher in those with CPPE. Pf lactate (cutoff ≥7.25 mmol/l) had a sensitivity of 79.3%, specificity 100%, positive predictive value 100%, and negative predictive value 89.1% for discriminating CPPE from TBE (area under the curve 0.947, p < 0.001, 95% confidence interval 0.89-0.99). CONCLUSIONS: Point-of-care Pf lactate measurements may have practical value in early separation of TBE or CPPE during initial thoracentesis, and warrants further investigation.

Successful treatment of pyopneumothorax with bronchopleural fistula using endobronchial Watanabe spigots.

Bronchopleural fistula (BPF) can complicate necrotizing pneumonia. Surgery would be indicated in patients who fail conservative management, yet this group is often of poor pulmonary function and general condition. Bronchial occlusion with endobronchial Watanabe spigots (EWS) can be a potential alternative treatment when the culprit bronchi can be isolated. In this case report, we describe a middle-aged gentleman who presented with necrotizing pneumonia complicated with pyopneumothorax with right upper lobe BPF, and who had failed to respond to chest drainage and antibiotics. EWS bronchial occlusion finally led to cessation of air leak, allowing removal of chest tube. EWS were removed uneventfully six months later. This case highlights the role of EWS in the management of BPF in patients with high surgical risk.

Novel Management of Peri-Aortitis after Endovascular Repair of Abdominal Aortic Aneurysm.

INTRODUCTION: The management of peri-aortitis, a rare complication after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAA), is described in a patient with a solitary kidney. REPORT: A 64 year old man who developed peri-aortitis after elective EVAR for a 6.6 cm infrarenal AAA is reported. Peri-aortitis was diagnosed two months after the procedure and was successfully treated with corticosteroids. CONCLUSION: There is no clear consensus on the best medical therapy for peri-aortitis secondary to EVAR. Peri-aortitis must be considered in patients with ongoing systemic symptoms of inflammation after EVAR, and early management is crucial to the early resolution of symptoms.