Genomic revolution: Transforming tuberculosis diagnosis and treatment with the use of Whole Genome Sequencing - A consensus statement.

Tuberculosis (TB) is a preventable, treatable, and curable disease. However, in 2020, 9∙9 million people were estimated to have developed tuberculosis, and 1.5 million people were estimated to have died from it. Whereas in India, 2.6 million were diagnosed with TB and 436,000 succumbed to TB in 2019. India (26%) is the major contributor to the global drop in TB cases. The COVID-19 pandemic has substantially reduced access to services for the diagnosis and treatment of TB, resulting in an increase in deaths and a reversal in global progress. [1] Presently, TB incidence is falling at a rate of 2% per year, obstructed mainly by the rearing pandemic of drug-resistant tuberculosis (DRTB). Particularly concerning is multi-drug resistant TB (MDRTB), defined as resistance towards isoniazid (INH) and rifampicin (RIF). [2] The World Health Organization (WHO) targeted to reduce worldwide TB incidence by 90% until 2035. (1) Early initiation of effective treatment based on susceptibility patterns of the Mycobacterium tuberculosis complex (MTBC) is considered key to successful TB control in countries with high DRTB incidence. Worldwide MDRTB treatment outcomes are poor, with cure rates less than 60% (2) due to the lack of comprehensive Drug Susceptibility Testing (DST) in most high MDRTB burden countries. This is leading to the inadequate anti-TB activity of the provided regimens (3-5), unlike regimens advised for DST assure optimal results. (6) In addition to resistances to the established regimens, the resistance to the newer DRTB drugs is increasing. On World TB Day 2022, Academy of Advanced Medical Education, Thyrocare Technologies Limited and HyastackAnalytics - IITB along with expert pulmonologist and renowned physicians from India convened for an advisory board meeting in Delhi on 20th March 2022 to discuss the role of Whole Genome Sequencing (WGS) in the diagnosis and management of TB. Objectives and specific topics relating to WGS in MDRTB were discussed, each expert shared their views, which led to a group discussion with a commitment to putting the patient first, and increasing their collective efforts, the organizations recognized that it is possible to make this goal a reality. The organizations involved in the discussion have declared their commitment to engaging in collaborative efforts to tackle DRTB detection efficiently. They advocate for strengthening access to WGS TB services, controlling and preventing TB, improving surveillance and drug resistance management, and investing in research and development. This Round Table serves as a framework to build on and ensure that the goal of ending TB is achievable with WGS services wherever needed. Post discussion, a uniform consensus was said to be arrived if more than 80% board members agreed to the statement. The present paper is the outcome of aspects presented and discussed in the advisory board meeting.

Imaging-based stratification of adult gliomas prognosticates survival and correlates with the 2021 WHO classification.

BACKGROUND: Because of the lack of global accessibility, delay, and cost-effectiveness of genetic testing, there is a clinical need for an imaging-based stratification of gliomas that can prognosticate survival and correlate with the 2021-WHO classification. METHODS: In this retrospective study, adult primary glioma patients with pre-surgery/pre-treatment MRI brain images having T2, FLAIR, T1, T1 post-contrast, DWI sequences, and survival information were included in TCIA training-dataset (n = 275) and independent validation-dataset (n = 200). A flowchart for imaging-based stratification of adult gliomas(IBGS) was created in consensus by three authors to encompass all adult glioma types. Diagnostic features used were T2-FLAIR mismatch sign, central necrosis with peripheral enhancement, diffusion restriction, and continuous cortex sign. Roman numerals (I, II, and III) denote IBGS types. Two independent teams of three and two radiologists, blinded to genetic, histology, and survival information, manually read MRI into three types based on the flowchart. Overall survival-analysis was done using age-adjusted Cox-regression analysis, which provided both hazard-ratio (HR) and area-under-curve (AUC) for each stratification system(IBGS and 2021-WHO). The sensitivity and specificity of each IBSG type were analyzed with cross-table to identify the corresponding 2021-WHO genotype. RESULTS: Imaging-based stratification was statistically significant in predicting survival in both datasets with good inter-observer agreement (age-adjusted Cox-regression, AUC > 0.5, k > 0.6, p < 0.001). IBGS type-I, type-II, and type-III gliomas had good specificity in identifying IDHmut 1p19q-codel oligodendroglioma (training - 97%, validation - 85%); IDHmut 1p19q non-codel astrocytoma (training - 80%, validation - 85.9%); and IDHwt glioblastoma (training - 76.5%, validation- 87.3%) respectively (p-value < 0.01). CONCLUSIONS: Imaging-based stratification of adult diffuse gliomas predicted patient survival and correlated well with 2021-WHO glioma classification.

A review of the Yasui operation with long-term follow-up of a case.

Yasui operation combines Norwood arch reconstruction with Rastelli operation for interrupted or hypoplastic aorta with aortic valvar atresia or hypoplasia with ventricular septal and two adequately sized ventricles, establishing biventricular repair. We present a case of aortic atresia, mitral hypoplasia, and ventricular septal defect (VSD) treated by Yasui procedure, and its long-term (108 months) follow-up and brief review of literature. Review of literature was done using keywords to search on "PubMed" and "Google Scholar." SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12055-021-01174-5.

Tuberculosis among prisoners & health care workers.

TB in prisons and among HCW is a major public health concern in countries having high burden of disease. Prompt detection of TB is must in prisons by screening on entry, passive screening, mass screening and contact screening via clinical evaluation, smear microscopy and chest X-rays. The new rapid diagnostic methods - True-NAAT, CBNAAT and Line Probe Assay are important tools in the diagnosis. Implementation of effective preventive measures at every steps in various settings, along with airborne infection control and protective measures for staff must be ensured.

An interesting case summary of tubercular pneumonia masquerading as viral pneumonia kept on extra-corporeal membrane oxygenation.

Mortality in patients with pulmonary tuberculosis remains high, especially in those who develop acute respiratory distress syndrome (ARDS). We herein, report a case of 40 year old female, with ARDS due to severe pulmonary tuberculosis. She was admitted in the intensive care unit of a tertiary care centre. Owing to very poor ABG report, she was intubated and put on Mechanical ventilator support. Bronchoscopy was performed and BAL was extracted, which showed no growth. Further deterioration of gas exchange prompted the decision to put her on ECMO. During her stay on ECMO, she developed massive inta-alveolar hemorrhage following which repeated bronchoscopic interventions were done to remove blood clots. BAL extracted on day 4 and day 8 showed growth of A. baumannii and K. pneumoniae respectively. But BALGeneXpert on day 8 came out to be positive for Mycobacterium Tuberculosis and subsequently ATT was added to her treatment regimen. Her alveolar hemorrhage continued to worsen and subsequently ECMO was removed. After 12 days of hospitalization, she went on to develop bradycardia and could not be rescued. Though the patient's life was lost, this case provided many insights on the use of ECMO in the management of ARDS due to Pulmonary tuberculosis and it should be considered as one of the treatment options.

Quality improvement can revolutionize tuberculosis care in India: A review.

BACKGROUND/PURPOSE: Access, cost and quality are limiting parameters of any healthcare delivery system. RNTCP (Revised National Tuberculosis Control Program) has largely addressed the access and cost issues, however the quality of care is a major hurdle in TB care today. METHODS: We propose using an evidence based method of quality improvement principles to address many quality issues ranging from delayed turnaround time in testing, to low patient satisfaction, and slow private sector engagement. RESULTS: We propose a 5 step approach to learning and conducting quality improvement at the district level. Step 1: Form a team and define the problem Step 2: Develop baseline data Step 3: Create a process map Step 4: Bring a change through a PDSA Plan-Do-Study-Act cycle Step 5: Prepare run charts. CONCLUSION: We cannot expect a different result by doing the same thing over and over again. This holds particularly true for the TB program in India. A major paradigm shift is necessary if we wish to achieve TB Free within our lifetimes. A shift from quality assurance to quality improvement offers this hope for change and TB elimination.

Contrast-enhanced Computed Tomography Imaging of Splenic Artery Aneurysms and Pseudoaneurysms: A Single-center Experience.

AIM: The aim of our study was to evaluate the computed tomography (CT) imaging features of splenic artery aneurysm and pseudoaneurysm and to identify the disease conditions related to the same. We also wanted to ascertain any relationship between these associated disease conditions and the imaging features of the aneurysms. MATERIALS AND METHODS: This retrospective study included patients diagnosed to have splenic artery aneurysms on contrast-enhanced CT examination between January 2001 and January 2016. Data were obtained from the picture archiving and communication system. The size, number, location, morphology, the presence of thrombosis, calcification, and rupture of the aneurysms were evaluated. RESULTS: A total of 45 patients were identified with a mean age of 45 years. Splenic artery aneurysms were idiopathic in 12 (26.6%) patients. In the remaining patients, the main associated disease conditions included pancreatitis 15 (33%), chronic liver disease with portal hypertension 8 (18%), and extrahepatic portal vein obstruction (EHPVO) 6 (13%). Statistically significant findings included the relationship between EHPVO and multiple aneurysms (P = 0.002), chronic liver disease and fusiform aneurysm (P = 0.008), and smaller size of idiopathic aneurysms (P < 0.001). CONCLUSION: Based on this study, splenic artery aneurysms were associated with a variety of etiologies. The characteristics of the aneurysms such as size, location, and morphology vary with the associated disease conditions. These variations may have implications for the management.

Collateral or fistula? Coronary artery as the primary source of pulmonary blood flow in a patient with pulmonary atresia and ventricular septal defect.

In patients with pulmonary atresia and ventricular septal defect (PA/VSD), a coronary artery being the primary source of pulmonary blood flow is a rare entity. We describe two cases of PA/VSD with coronary-to-pulmonary artery fistula with emphasis on the role of Computed Tomographic Angiography (CTA) in depicting all the sources of pulmonary blood supply, to predict surgical management and need for unifocalization of Major Aortopulmonary Collateral Arteries (MAPCA's).

Efficacy and safety of ipratropium bromide/salbutamol sulphate administered in a hydrofluoroalkane metered-dose inhaler for the treatment of COPD.

BACKGROUND: The use of chlorofluorocarbons (CFCs) has contributed to the depletion of the stratospheric ozone layer resulting in serious health concerns. Ipratropium bromide/salbutamol sulphate CFC-pressurized metered-dose inhalers (IB/SAL-CFC pMDI) have been in widespread use for many years without any apparent ill consequences. This combination has now been reformulated using the hydrofluoroalkane (HFA) propellant. This study sought to establish the clinical noninferiority of a new HFA-containing IB/SAL pMDI to the conventional IB/SAL-CFC pMDI in subjects with mild/moderate COPD. METHODS: This was a randomized, double-blind, parallel-group, multicenter study in two consecutive periods: a 14-day run-in period followed by a 85-day treatment period. Eligible mild-to-moderate stable COPD subjects aged 40-75 years were enrolled into the study and entered the run-in period during which subjects withdrew all the bronchodilators, except for salbutamol as rescue medication. Subjects were randomized to 85 days treatment with either IB/SAL-HFA or IB/SAL-CFC, 20 µg qid. RESULTS: Of the 290 randomized patients, 249 completed the study. The primary efficacy variable was the change in forced expiratory volume in one second from predose to 60 minutes after dosing on day 85. At the end of the treatment period, the adjusted mean change in forced expiratory volume in one second at 60 minutes was 123 mL in the IB/SAL-HFA pMDI group and 115 mL in the IB/SAL-CFC pMDI group. Because the lower limit of the 95% confidence interval for the between-group difference (-62 mL) was well within the noninferiority margin (-100 mL), the HFA formulation was deemed clinically noninferior to the CFC formulation. This finding was supported by secondary efficacy assessments. Both formulations of IB/SAL were well tolerated during the prolonged multiple dosing. CONCLUSION: It is concluded that IB/SAL-HFA pMDI provides effective bronchodilation of similar degree to that achieved with IB/SAL-CFC pMDI. Therefore, IB/SAL-HFA pMDI is a valuable alternative to IB/SAL-CFC pMDI.

Vaccines against tuberculosis: A review.

Tuberculosis (TB) has taken toll of many lives, therefore a need of effective TB vaccine, which can provide sufficient immunity to prevent developing of disease has been felt for a longer time. BCG, the only available vaccine, though prevents against severe form of primary tuberculosis in paediatric population, failed to have its efficacy in pulmonary patients. Few candidates are in the pipeline undergoing clinical trial. An extensive research is needed to ensure their safety and efficacy before their acceptance as a TB vaccine to be incorporated in national immunization programmes.

A randomized, comparative, multicentric clinical trial to assess the efficacy and safety of zileuton extended-release tablets with montelukast sodium tablets in patients suffering from chronic persistent asthma.

Leukotriene (LT) modifiers are anti-inflammatory drugs that are useful as an add-on therapy with first-line asthma-controller medications. This group includes LT synthesis inhibitors (eg, Zileuton) and receptor antagonists (eg, Montelukast), whose direct comparative clinical data are not available. This study was conducted to assess the comparative efficacy and safety of orally administered Zileuton extended-release (ER) with Montelukast sodium in patients suffering from chronic persistent asthma. Patients of 18-65 years of age with mild to moderate chronic stable asthma were randomized to treatment with Zileuton ER 2400 mg/d or Montelukast 10 mg/d for 12 weeks. Peak expiratory flow rate (PEFR) and asthma symptoms (cough, wheeze, chest tightness, and shortness of breath each on a 4-point scale) were assessed on monthly scheduled out-patient visits. Safety assessments by clinical and laboratory parameters were carried out during the course of the study. Among 210 patients eligible for efficacy assessment, PEFR improved by 64.8 ± 52.8 (95% confidence interval: 54.8-74.7) L/min with Zileuton ER (n = 109) and 40.6 ± 47.5 (31.3-49.9) L/min with Montelukast (n = 101; P < 0.001), whereas percent improvements were 27.0% (22.6%-31.5%) versus 18.4% (14.1%-22.7%), respectively (P = 0.006). Zileuton ER lead to ≥12% PEFR improvements in 74 of 109 [67.9% (59.1%-76.7%)] patients, whereas the same was noted in 52 of 101 [51.5% (41.7%-61.2%)] patients receiving Montelukast (P = 0.015). The reduction in the mean overall symptom intensity score was also significantly better with Zileuton ER [-5.0 ± 2.1 (4.6-5.4) versus -4.2 ± 2.3 (3.8-4.7)] (P = 0.018); however, the same was not observed for the decline in the individual symptom scores. A lesser but not significantly different adverse event rate was reported in the Zileuton ER group than the Montelukast group with the commonest events being headache and gastrointestinal effects in both the groups. Thus, Zileuton ER seems to be more efficacious than Montelukast and well tolerated for the treatment of mild to moderate chronic persistent asthma in adult patient population. Further studies can elucidate the comparative treatment benefits of these LT modifiers in asthma management.