Biomarkers in diagnosing and therapeutic monitoring of tuberculosis: a review.

Tuberculosis (TB) continues to pose a significant health challenge worldwide, emphasizing the importance of prompt diagnosis and efficient monitoring of treatment outcomes for effective disease control. Biomarkers have become increasingly important in the realm of TB diagnoses and treatment. The objective of this comprehensive review is to examine the present state of biomarkers employed in the diagnosis of TB, monitoring the response to treatment, and predicting treatment outcomes. In this study, we undertake a comprehensive examination of the diverse biomarkers utilized in TB diagnoses, spanning molecular, immunological, and other novel methodologies. Furthermore, we examine the potential of biomarkers in the context of therapeutic monitoring, assessment of treatment effectiveness, and anticipation of drug resistance. Additionally, this paper presents future prospects regarding the utilization of biomarkers in the therapy of tuberculosis.

Efficacy and tolerability of a 4-month ofloxacin-containing regimen compared to a 6-month regimen in the treatment of patients with superficial lymph node tuberculosis: a randomized trial.

BACKGROUND: Tuberculosis (TB) lymphadenitis is the most common form of extra-pulmonary TB, and the treatment duration is six months. This non-inferiority based randomized clinical trial in South India evaluated the efficacy and safety of a four-month ofloxacin containing regimen in tuberculosis lymphadenitis (TBL) patients. METHODS: New, adult, HIV-negative, microbiologically and or histopathologically confirmed superficial lymph node TB patients were randomized to either four-month oflaxacin containing test regimen [ofloxacin (O), isoniazid (H), rifampicin (R), pyrazinamide (Z) -2RHZO daily/ 2RHO thrice-weekly] or a six-month thrice-weekly control regimen (2HRZ, ethambutol/4RH). The treatment was directly observed. Clinical progress was monitored monthly during and up to 12 months post-treatment, and thereafter every three months up to 24 months. The primary outcome was determined by response at the end of treatment and TB recurrence during the 24 months post-treatment. RESULTS: Of the 302 patients randomized, 298 (98.7%) were eligible for modified intention-to-treat (ITT) analysis and 294 (97%) for per-protocol (PP) analysis. The TB recurrence-free favourable response in the PP analysis was 94.0% (95% CI: 90.1-97.8) and 94.5% (95% CI: 90.8-98.2) in the test and control regimen respectively, while in the ITT analysis, it was 92.7% and 93.2%. The TB recurrence-free favourable response in the test regimen was non-inferior to the control regimen 0.5% (95% CI: -4.8-5.9) in the PP analysis based on the 6% non-inferiority margin. Treatment was modified for drug toxicity in two patients in the test regimen, while one patient had a paradoxical reaction. CONCLUSION: The 4-month ofloxacin containing regimen was found to be non-inferior and as safe as the 6-month thrice-weekly control regimen.

Barriers to research progress for perioperative care practitioners working in cardiothoracic surgery.

Policy and research literature worldwide support the need to build research capacity and capability among non-medical practitioners within healthcare systems. However, there exists a paucity of evidence on whether practitioners in cardiothoracic surgery are attuned to this and on what barriers or enablers exist. A survey was carried out with non-medical practitioners working in cardiothoracic surgery in the United Kingdom to explore attitudes towards health research and audit, and to identify current challenges and barriers to surgical research and audit as perceived by cardiothoracic nurses and allied health professionals. A total of 160 completed questionnaires were returned. 99% of respondents supported the need for research and believed that evidence-based surgical care improves outcomes for patients. Seventy-two percent reported that their employer motivates them to take part in national research or audit but, only 22% were allocated time to do so within their role; 96% reported their interest in being involved in research and audit, yet only 30% believed they had the skills to undertake research, and 96% reported needing additional training. More work is needed to increase awareness, capacity and capability among cardiothoracic surgery care practitioners, and indeed other specialities to achieve research progress.

Resistance Profiles to Second-Line Anti-Tuberculosis Drugs and Their Treatment Outcomes: A Three-Year Retrospective Analysis from South India.

Background: Patients with first-line drug resistance (DR) to rifampicin (RIF) or isoniazid (INH) as a first-line (FL) line probe assay (LPA) were subjected to genotypic DST using second-line (SL) LPA to identify SL-DR (including pre-XDR) under the National TB Elimination Program (NTEP), India. SL-DR patients were initiated on different DR-TB treatment regimens and monitored for their outcomes. The objective of this retrospective analysis was to understand the mutation profile and treatment outcomes of SL-DR patients. Materials and Methods: A retrospective analysis of mutation profile, treatment regimen, and treatment outcome was performed for SL-DR patients who were tested at ICMR-NIRT, Supra-National Reference Laboratory, Chennai between the years 2018 and 2020. All information, including patient demographics and treatment outcomes, was extracted from the NTEP Ni-kshay database. Results: Between 2018 and 2020, 217 patients out of 2557 samples tested were identified with SL-DR by SL-LPA. Among them, 158/217 were FQ-resistant, 34/217 were SLID-resistant, and 25/217 were resistant to both. D94G (Mut3C) of gyrA and a1401g of rrs were the most predominant mutations in the FQ and SLID resistance types, respectively. Favorable (cured and treatment complete) and unfavorable outcomes (died, lost to follow up, treatment failed, and treatment regimen changed) were recorded in a total of 82/217 and 68/217 patients in the NTEP Ni-kshay database. Conclusions: As per the testing algorithm, SL- LPA is used for genotypic DST following identification of first-line resistance, for early detection of SL-DR in India. The fluoroquinolone resistance pattern seen in this study population corelates with the global trend. Early detection of fluoroquinolone resistance and monitoring of treatment outcome can help achieve better patient management.

Lung volume reduction surgery versus endobronchial valves: a randomised controlled trial.

BACKGROUND: Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (BLVR) with endobronchial valves can improve outcomes in appropriately selected patients with emphysema. However, no direct comparison data exist to inform clinical decision making in people who appear suitable for both procedures. Our aim was to investigate whether LVRS produces superior health outcomes when compared with BLVR at 12 months. METHODS: This multicentre, single-blind, parallel-group trial randomised patients from five UK hospitals, who were suitable for a targeted lung volume reduction procedure, to either LVRS or BLVR and compared outcomes at 1 year using the i-BODE score. This composite disease severity measure includes body mass index, airflow obstruction, dyspnoea and exercise capacity (incremental shuttle walk test). The researchers responsible for collecting outcomes were masked to treatment allocation. All outcomes were assessed in the intention-to-treat population. RESULTS: 88 participants (48% female, mean±sd age 64.6±7.7 years, forced expiratory volume in 1 s percent predicted 31.0±7.9%) were recruited at five specialist centres across the UK and randomised to either LVRS (n=41) or BLVR (n=47). At 12 months follow-up, the complete i-BODE was available in 49 participants (21 LVRS/28 BLVR). Neither improvement in the i-BODE score (LVRS -1.10±1.44 versus BLVR -0.82±1.61; p=0.54) nor in its individual components differed between groups. Both treatments produced similar improvements in gas trapping (residual volume percent predicted: LVRS -36.1% (95% CI -54.6- -10%) versus BLVR -30.1% (95% CI -53.7- -9%); p=0.81). There was one death in each treatment arm. CONCLUSION: Our findings do not support the hypothesis that LVRS is a substantially superior treatment to BLVR in individuals who are suitable for both treatments.

True thymic hyperplasia causing pure red cell aplasia: a case report.

Pure red cell aplasia caused by true thymic hyperplasia is extremely rare. We report the case of a 25-year-old female diagnosed with pure red cell aplasia. Following a thymectomy confirming true thymic hyperplasia and corticosteroid therapy, complete response was achieved. Patients diagnosed with pure red cell aplasia should be investigated with a computerized tomographic scan to assess for thymic pathology and if present, this should be resected. Follow-up is essential to monitor for recurrence.

Utilization of High-pressure Suction for EBUS-TBNA Sampling in Suspected Lung Cancer.

BACKGROUND: Sample adequacy for immediate molecular testing is paramount in lung cancer. To date, several endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) sampling setups have been evaluated, however, the utilization of high-pressure suction (HPS) has not yet been reported.The aim of this study was to evaluate the utilization of HPS onto the needle and its effect on sample volume and adequacy for molecular testing in patients with suspected lung cancer. METHODS: We retrospectively analyzed 128 consecutive EBUS-TBNA performed for suspected lung cancer. This was confirmed in 109 patients. Other diagnoses confirmed in 12, and 7 referred for surgery. Sixty-three patients (89 targets) had HPS (May to September 2020), and compared with 46 (72 targets) who had standard vacuum syringe suction (October 2019 to March 2020). Several parameters and outcomes evaluated, such as number of needle passes, needle strokes, needle size, target size, positron emission tomography avidity, procedure time, blood content score, sample volume, adequacy for molecular testing, as well as baseline patient characteristics and complication rate. RESULTS: There was no difference between the 2 groups in all baseline parameters and characteristics. In multivariable analysis, HPS was associated with significantly higher sample volume (11.2 vs. 9.1 mm3, P=0.036) and less additional procedures to achieve full molecular profiling (2/52 vs. 7/40, P=0.042), in necrotic targets of non-small cell lung cancer. Diagnostic yields were comparable. CONCLUSION: HPS appears to be simple, no-cost, and safe, promising higher sample volume compared with vacuum syringe suction, and also appears to be associated with higher success of full molecular testing with less additional procedures, in non-small cell lung cancer necrotic targets.

Predictors of unfavorable responses to therapy in rifampicin-sensitive pulmonary tuberculosis using an integrated approach of radiological presentation and sputum mycobacterial burden.

INTRODUCTION: Despite the exalted status of sputum mycobacterial load for gauging pulmonary tuberculosis treatment and progress, Chest X-rays supplement valuable information for taking instantaneous therapeutic decisions, especially during the COVID-19 pandemic. Even though literature on individual parameters is overwhelming, few studies have explored the interaction between radiographic parameters denoting severity with mycobacterial burden signifying infectivity. By using a sophisticated approach of integrating Chest X-ray parameters with sputum mycobacterial characteristics, evaluated at all the three crucial time points of TB treatment namely pre-treatment, end of intensive phase and completion of treatment, utilizing the interactive Cox Proportional Hazards model, we aimed to precisely deduce predictors of unfavorable response to TB treatment. MATERIALS AND METHOD: We extracted de-identified data from well characterized clinical trial cohorts that recruited rifampicin-sensitive Pulmonary TB patients without any comorbidities, taking their first spell of anti-tuberculosis therapy under supervision and meticulous follow up for 24 months post treatment completion, to accurately predict TB outcomes. Radiographic data independently obtained, interpreted by two experienced pulmonologists was collated with demographic details and, sputum smear and culture grades of participants by an independent statistician and analyzed using the Cox Proportional Hazards model, to not only adjust for confounding factors including treatment effect, but also explore the interaction between radiological and bacteriological parameters for better therapeutic application. RESULTS: Of 667 TB patients with data available, cavitation, extent of involvement, lower zone involvement, smear and culture grade at baseline were significant parameters predisposing to an unfavorable TB treatment outcome in the univariate analysis. Reduction in radiological lesions in Chest X-ray by at least 50% at 2 months and 75% at the end of treatment helped in averting unfavorable responses. Smear and Culture conversion at the end of 2 months was highly significant as a predictor (p<0.001). In the multivariate analysis, the adjusted hazards ratios (HR) for an unfavorable response to TB therapy for extent of involvement, baseline cavitation and persistence (post treatment) were 1.21 (95% CI: 1.01-1.44), 1.73 (95% CI: 1.05-2.84) and 2.68 (95% CI: 1.4-5.12) respectively. A 3+ smear had an HR of 1.94 (95% CI: 0.81-4.64). Further probing into the interaction, among patients with 3+ and 2+ smears, HRs for cavitation were 3.26 (95% CI: 1.33-8.00) and 1.92 (95% CI: 0.80-4.60) while for >2 zones, were 3.05 (95% CI: 1.12-8.23) and 1.92 (95% CI: 0.72-5.08) respectively. Patients without cavitation, zonal involvement <2, and a smear grade less than 2+ had a better prognosis and constituted minimal disease. CONCLUSION: Baseline Cavitation, Opacities occupying >2 zones and 3+ smear grade individually and independently forecasted a poorer TB outcome. The interaction model revealed that Zonal involvement confined to 2 zones, without a cavity and smear grade up to 2+, constituting "minimal disease", had a better prognosis. Radiological clearance >50% along with smear conversion at the end of intensive phase of treatment, observed to be a reasonable alternative to culture conversion in predicting a successful outcome. These parameters may potentially take up key positions as stratification factors for future trials contemplating on shorter TB regimens.

Use of pedicled latissimus dorsi flap in anterior chest wall reconstruction.

Successful surgical management of chest wall tumours relies on extensive chest wall resection with adequate margins. In large complex tumours, return to form and function is determined by appropriate skeletal and soft tissue reconstruction of the chest wall defect. We report an original case of a large 11×16×3 cm ulcerative basosquamous carcinoma of the anterior chest wall. Soft tissue reconstruction was performed with a unilateral pedicled latissimus dorsi flap. A multidisciplinary approach between thoracic and plastic surgeons was used in the planning, intraoperative and follow-up periods. This case highlights a good long-term functional and cosmetic outcome in complex chest wall reconstruction as a result of successful cross-specialty collaboration.

Uniportal VATS retrieval of an endobronchial coil migrated through pericardium.

Endobronchial insertion of nitinol coils is a minimally invasive treatment strategy for selected patients with advanced emphysema. Although coil migration into the pleural space has been described by Marchetti et al. (Endobronchial coil penetration into the pleural space. Thorax 2018;73:890-1) [ 1], breach through the pericardium has not been reported to date.

Impact of coronavirus 2019 (COVID-19) on training and well-being in subspecialty surgery: A national survey of cardiothoracic trainees in the United Kingdom.

OBJECTIVES: The coronavirus 2019 (COVID-19) pandemic has overwhelmed health care systems and disrupted routine care internationally. Health care workers face disruption to their work routines and professional development, as well as an elevated risk of infection and morbidity. We sought to establish the impact of the COVID-19 pandemic on the well-being, practice, and progression of all trainees in cardiothoracic surgery in the United Kingdom. METHODS: A 31-item questionnaire was designed, validated, and disseminated via e-mail and an instant-messaging platform. RESULTS: In total, 76 (of 118, 64%) cardiothoracic surgical trainees responded, representing all training grades and programs nationally; 48 (63%) and 24 (32%) were concerned about their physical and mental health, respectively, 25 (33%) had taken time off work due to COVID-19, 65 (86%) had treated patients with COVID-19, 36 of whom (55%) were wearing satisfactory personal protective equipment at the time, 41 (54%) remain concerned about personal protective equipment provision at their institution, 42 (55%) had been redeployed to cover other specialties, and 23 (30%) had encountered ethical dilemmas related to care of patients. There was a significant impact on time spent in outpatient clinics (44% reduction), multidisciplinary team meetings (79% reduction), and operating theaters (78% reduction). In total, 67 (88%) of respondents were concerned about the impact on their training, and 54 (71%) felt that the deviation may require an extension in their planned training time. CONCLUSIONS: The duration and impact of the current pandemic is, as yet, uncertain. Timely sharing of experiences, concerns, and expectations will inform health care and education policy and influence practice in the pandemic era and beyond.

Training cardiothoracic surgeons of the future: The UK experience.

OBJECTIVE: The study aimed to assess targeted simulation courses, including live animal operating, as complementary training tools with regard to 2 key surgical skills in early cardiothoracic surgeon training. METHODS: Twenty UK surgical trainees (equivalent to cardiothoracic surgery resident physicians in the United States) in their first year of residency training were evaluated. Assessment of skills in pulmonary wedge resection and cardiopulmonary bypass were undertaken before and after 2 boot camp-style courses, including live animal operating (boot camp 1 and boot camp 2). Resident performance was evaluated by surgical trainers using objective structured assessment of technical skills matrices. Trainers completed a survey on skill development and trainer confidence in the trainee precourse and postcourse. RESULTS: Trainee assessment scores pre- and postcourses were analyzed using a 2-tailed Wilcoxon signed-rank test demonstrating a significant improvement in trainee performance in boot camp 1 in performing cardiopulmonary bypass (median score, 21 precourse and 28 postcourse; P = .001) and pulmonary wedge resection (median score, 25 precourse and 32 postcourse; P = .012), and in boot camp 2, in performing cardiopulmonary bypass (median score, 28 precourse and 30.5 postcourse; P = .018) and pulmonary wedge resection (median score, 31.5 precourse and 37 postcourse; P = .018). Trainers reported increased confidence and decision-making competency of residents and increased confidence of trainers to allow more participation in management. It was found that 83.3% of trainers would support trainee attendance in subsequent years. CONCLUSIONS: Live animal operating as a component of targeted cardiothoracic surgery skill training courses significantly improves technical skills, builds confidence of surgical trainers in resident physicians' practice, and should be supported by the surgery community.

Daily vs Intermittent Antituberculosis Therapy for Pulmonary Tuberculosis in Patients With HIV: A Randomized Clinical Trial.

Importance: The benefit of daily over thrice-weekly antituberculosis therapy among HIV-positive patients with pulmonary tuberculosis (TB) who are receiving antiretroviral therapy remains unproven. Objective: To compare the efficacy and safety of daily, part-daily, and intermittent antituberculosis therapy regimens in the treatment of HIV-associated pulmonary TB. Design, Setting, and Participants: This open-label, randomized clinical trial was conducted by the National Institute for Research in Tuberculosis, south India. Adults infected with HIV with newly diagnosed, culture-positive, pulmonary TB were enrolled between September 14, 2009, and January 18, 2016. Interventions: Patients were randomized to daily, part-daily, and intermittent antituberculosis therapy regimens, stratified by baseline CD4 lymphocyte count and sputum smear grade. Antiretroviral therapy was initiated as per national guidelines. Clinical and sputum microbiological examinations of patients were performed monthly until 18 months after randomization. Adverse events were recorded using standard criteria. Main Outcomes and Measures: The primary outcome was favorable response, defined as treatment completion with all available sputum cultures negative for Mycobacterium tuberculosis during the last 2 months of treatment. Unfavorable responses included treatment failures, dropouts, deaths, and toxic effects among regimens. Results: Of 331 patients (251 [76%] male; mean [SD] age, 39 [9] years; mean [SD] HIV viral load, 4.9 [1.2] log10 copies/mL; and median [interquartile range] CD4 lymphocyte count, 138 [69-248] cells/µL), favorable responses were experienced by 91% (89 of 98), 80% (77 of 96), and 77% (75 of 98) in the daily, part-daily, and intermittent regimens, respectively. With the difference in outcome between daily and intermittent regimens crossing the O'Brien-Fleming group sequential boundaries and acquired rifampicin resistance emergence (n = 4) confined to the intermittent group, the data safety monitoring committee halted the study. A total of 18 patients died and 18 patients dropped out during the treatment period in the 3 regimens. Six, 4, and 6 patients in the daily, part-daily, and intermittent regimens, respectively, had TB recurrence. Conclusions and Relevance: Among HIV-positive patients with pulmonary TB receiving antiretroviral therapy, a daily anti-TB regimen proved superior to a thrice-weekly regimen in terms of efficacy and emergence of rifampicin resistance. Trial Registration: clinicaltrials.gov Identifier: NCT00933790.

Implementation of a novel portfolio of structured, curriculum-aligned, simulation-based, cardiothoracic surgery training courses: Evolving the delivery of surgical education.

OBJECTIVE: The provision of high-quality cardiothoracic surgical training faces many challenges. This has generated an increased interest in simulation-based learning, which can provide a less stressful environment for deliberate practice. We developed a comprehensive, structured program of knowledge and simulation-based learning aligned to the official cardiothoracic surgery curriculum. METHODS: A portfolio of 10 curriculum-aligned training courses was designed for cardiothoracic surgical trainees during their 6-year training program. The courses were delivered through a multitude of education methods, including live porcine operating simulation models, and were evaluated through a series of quantitative (5-point Likert-scale) and qualitative assessments. The trainees (n = 15-21 per course) also completed pre- and postsession self-confidence and competency levels for each training episode of knowledge and skill, respectively. In addition, board examination pass rates were assessed in the 3-year periods before and after implementation of the courses. RESULTS: Quantitative analysis of the trainees' feedback demonstrated an extremely positive view of the portfolio of the simulation-based training courses with excellent satisfaction scores (out of 5) for teaching sessions (4.44 ± 0.07), faculty (4.64 ± 0.07), content and materials (4.63 ± 0.07), and facilities (4.73 ± 0.05). The courses have shown a significant improvement in the post-self-confidence (7.98 ± 0.13 vs 5.62 ± 0.20, P < .01) and perceived self-competency (8.10 ± 0.10 vs 5.67 ± 0.11, P < .01) scores for all courses. Examination pass rates significantly improved in the 3-year period after attendance at the courses (94.82% ± 2.34% vs 76.26% ± 3.23%, P < .005). CONCLUSIONS: This study has described the implementation of the only extensive program of structured simulation-based courses that has been developed to complement clinical training in cardiothoracic surgery.

VATS and open chest surgery in diagnosis and treatment of benign pleural diseases.

A negative pressure normally exists between the visceral and parietal pleurae in the lungs, which can act as vacuum for fluid, air and small particles from different parts of the body, allowing them to move into the pleural space and be retained in it, thus resulting to different manifestations of pleural disorders. A pleural effusion is the result of fluid collection between the parietal and visceral pleural surfaces. The most common cause in developed countries is congestive heart failure, followed by pneumonia and malignancy. It is highly important that a systematic approach is undertaken during the investigation of pleural effusions. Treatment should be based on the nature of the effusion and underlying condition, while undiagnosed patients should remain under surveillance. Pleural infection is a serious clinical condition which affects approximately 65,000 patients every year in the UK and can result in mortality in rates as high as 20%. The selection of treatment as well as timing of intervention remains a debatable issue among pulmonologists and thoracic surgeons. Surgical intervention aims to control sepsis, by facilitating evacuation of necrotic material from the pleural space, and obliterate the empyema cavity, by allowing the trapped lung to re-expand via peeling of the organised cortex from its visceral pleura. Thoracoscopic surgery offers the advantages of visual assessment of the pleural space and direct tissue sampling and it can be useful for the diagnosis of unknown pleural effusions and in the management of complicated collections. Open thoracotomy remains the gold standard, however with the advancement of thoracoscopic instruments and techniques, minimally invasive approaches provide comparable outcomes and have been taking over the management of benign pleural diseases.

Long-term survival and symptomatic relief in lower lobe lung volume reduction surgery.

OBJECTIVES: Lung volume reduction surgery (LVRS) has been demonstrated to provide symptomatic relief and improve lung function in patients with end-stage emphysema. The National Emphysema Treatment Trial specifically noted functional benefits in patients with predominantly upper lobe emphysema and demonstrated improvement in quality-of-life parameters, in patients with non-upper lobe emphysema and a low-baseline exercise capacity. We aimed to investigate whether physiological and health status benefits correlated with lower lobe LVRS. METHODS: A retrospective analysis was performed from our prospectively collected patient database. A total of 36 patients with severe, non-upper lobe predominant emphysema underwent lower lobe LVRS in our institution, over a 20-year period. The assessments consisted of measurements of body mass index, pulmonary function tests and health-related quality of life using the Short Form 36-item questionnaires. RESULTS: Forced expiratory volume in 1 s was seen to improve 3 months [coefficient of time = 1.55 (0.88, 2.21); P < 0.0001] after the procedure, maintained until the first 6 months [0.48 (0.12, 0.85); P = 0.010], decline over the second half of the first year and gradually return to preoperative levels after 2 years, while residual volume to total lung capacity (%) ratio was seen to follow a similar pattern with significant decrease from baseline after 3 months [coefficient of time = -1.76 (-2.75, -0.76); P = 0.001] and 6 months [-1.05 (-1.51, -0.59); P < 0.0001]. Quality-of-life improvements were mainly noted in physical components. CONCLUSIONS: Contrary to a widely held misconception following the National Emphysema Treatment Trial that lower lobe lung volume reduction does not offer significant benefits to patients with non-upper lobe predominant emphysema, we feel justified in offering lower lobe LVRS in these patients when they meet the same selection criteria as upper lobe LVRS.