Screening for Lung Cancer in India: Expert Opinion Statement.

Lung cancer (LC) has the highest rate of disability-adjusted life years (DALY) of all cancers in India. A large majority of patients with LC present with advanced disease, resulting in poor survival rates. Early diagnosis can improve survival outcomes as the patients can be treated with curative intent. The National Lung Screening Trial (NLST), in 53,454 persons at high risk for LC in the US, showed a 20% (95% confidence interval of 6.8-26.7; p = 0.004) relative reduction in LC-specific mortality in the patients screened with low-dose computed tomography (LDCT) compared with chest X-ray. To date, India does not have a formal LC screening (LCS) program. As a panel of experts, we reviewed a synthesis of a targeted literature search on the burden of LC, the current status of diagnosis of LC, barriers to early diagnosis, current referral pathways, LC risk patterns, use of artificial intelligence (AI) and risk calculators for risk assessment, and a multidisciplinary team (MDT) approach to diagnosis LC. We used the existing international LCS guidelines, data from published literature, and clinical experience to depict the characteristics of the population at risk of LC in India-young age (<40 years), smoking, especially the predominance of bidi smoking (an indigenous form of tobacco smoking), exposure to biomass fuel smoke, especially in rural women, and air pollution being the prominent features. LC in India is characterized by a higher rate of driver mutations and adenocarcinomatous histology. Here, we present the expert opinion on risk-based LCS in India and discuss the challenges, facilitators, and research priorities for the effective rollout of LCS in India.

Low-dose CT with metal artifact reduction in arthroplasty imaging: a cadaveric and clinical study.

OBJECTIVE: To determine whether a simulated low-dose metal artifact reduction (MAR) CT technique is comparable with a clinical dose MAR technique for shoulder arthroplasty evaluation. MATERIALS AND METHODS: Two shoulder arthroplasties in cadavers and 25 shoulder arthroplasties in patients were scanned using a clinical dose (140 kVp, 300 qrmAs); cadavers were also scanned at half dose (140 kVp, 150 qrmAs). Images were reconstructed using a MAR CT algorithm at full dose and a noise-insertion algorithm simulating 50% dose reduction. For the actual and simulated half-dose cadaver scans, differences in SD for regions of interest were assessed, and streak artifact near the arthroplasty was graded by 3 blinded readers. Simulated half-dose scans were compared with full-dose scans in patients by measuring differences in implant position and by comparing readers' grades of periprosthetic osteolysis and muscle atrophy. RESULTS: The mean difference in SD between actual and simulated half-dose methods was 2.42 HU (95% CI [1.4, 3.4]). No differences in streak artifact grades were seen in 13/18 (72.2%) comparisons in cadavers. In patients, differences in implant position measurements were within 1° or 1 mm in 149/150 (99.3%) measurements. The inter-reader agreement rates were nearly identical when readers were using full-dose (77.3% [232/300] for osteolysis and 76.9% [173/225] for muscle atrophy) and simulated half-dose (76.7% [920/1200] for osteolysis and 74.0% [666/900] for muscle atrophy) scans. CONCLUSION: A simulated half-dose MAR CT technique is comparable both quantitatively and qualitatively with a standard-dose technique for shoulder arthroplasty evaluation, demonstrating that this technique could be used to reduce dose in arthroplasty imaging.

A randomized, double-blind, placebo-controlled, Phase 2b study to evaluate the safety and efficacy of recombinant human soluble thrombomodulin, ART-123, in patients with sepsis and suspected disseminated intravascular coagulation.

OBJECTIVES: To determine the safety and efficacy of recombinant thrombomodulin (ART-123) in patients with suspected sepsis-associated disseminated intravascular coagulation. DESIGN: Phase 2b, international, multicenter, double-blind, randomized, placebo-controlled, parallel group, screening trial. SETTING: Two hundred and thirty-three ICUs in 17 countries. PATIENTS: All adult patients admitted with sepsis and suspected disseminated intravascular coagulation as assessed using a modified International Society on Thrombosis and Hemostasis score. INTERVENTIONS: Patients were randomized to receive IV ART-123 (0.06 mg/kg/d) for 6 days or placebo, in addition to standard of care. The primary endpoint was reduction in mortality. Secondary endpoints included reversal of overt disseminated intravascular coagulation and reduction in disease severity. MEASUREMENTS AND MAIN RESULTS: A total of 750 patients were randomized, nine of whom did not receive the allocated treatment so that 371 patients received ART-123 and 370 received placebo. There were no meaningful differences between the two groups in any of the baseline variables. Twenty-eight-day mortality was 17.8% in the ART-123 group and 21.6% in the placebo group (Cochran-Mantel-Haenszel two-sided p value of 0.273 in favor of ART-123, which met the predefined statistical test for evidence suggestive of efficacy). There were no statistically significant differences in event-free and alive days between the two groups. d-dimer, prothrombin fragment F1.2 and TATc concentrations were lower in the ART-123 group than in the placebo group. There were no differences between the two groups in organ function, inflammatory markers, bleeding or thrombotic events or in the development of new infections. In post hoc analyses, greatest benefit from ART-123 was seen in patients with at least one organ system dysfunction and an international normalized ratio greater than 1.4 at baseline. CONCLUSIONS: ART-123 is a safe intervention in critically ill patients with sepsis and suspected disseminated intravascular coagulation. The study provided evidence suggestive of efficacy supporting further development of this drug in sepsis-associated coagulopathy including disseminated intravascular coagulation. Future study should focus on using ART-123 in the subgroup of patients most likely to respond to this agent.

Real-life effectiveness of budesonide/formoterol maintenance and reliever therapy in asthma patients across Asia: SMARTASIA study.

BACKGROUND: The use of budesonide/formoterol in a single inhaler for both maintenance and reliever therapy is a recommended option for treatment of persistent asthma not responding well to inhaled corticosteroid (ICS) alone. METHODS: This was a multi-centre open-label study on patients whose asthma condition remained inadequately controlled by various asthma treatments other than budesonide/formoterol. After a 2-week run-in period, eligible patients underwent a 12-week treatment period with budesonide/formoterol (Symbicort SMART(®), 160/4.5 µg) twice daily plus as needed. Patient's asthma control and quality of life were assessed using the 5-item Asthma Control Questionnaire (ACQ-5) and the standardized Asthma Quality of Life Questionnaire (AQLQ-S), respectively. RESULTS: A total of 862 eligible asthma patients who have had asthma for a mean duration of 10.73 ± 12.03 years entered a 12-week treatment with budesonide/formoterol maintenance and reliever therapy. During treatment, ACQ-5 score improved significantly by 0.58 ± 0.93 (95% CI, 0.51 to 0.64, P < 0.0001) from the baseline level of 1.62 ± 1.00. AQLQ(S) score improved by 0.70 ± 0.89 (95% CI, 0.64 to 0.76, P < 0.0001) from baseline. Asthma symptom score was also reduced significantly (P < 0.0001); between run-in and treatment periods, night- and day-time symptom scores were reduced by 0.32 ± 0.54 (95% CI, 0.28 to 0.35) and 0.30 ± 0.52 (95% CI, 0.27 to 0.34), respectively. The percentage of nights with awakenings due to asthma symptoms was reduced by 11.09 ± 26.13% (95% CI, 9.34 to 12.85%), while the percentage of asthma-control and symptom-free days increased by 20.90 ± 34.40% (95% CI, 18.59 to 23.21%) and 23.89 ± 34.62% (95% CI, 21.56 to 26.21%), respectively (P < 0.0001). Together with the improvement in asthma control, the number of night- and day-time inhalations of as-needed reliever medication decreased by 0.30 ± 0.82 (95% CI, 0.24 to 0.35) inhalations and 0.30 ± 0.97 (95% CI, 0.23 to 0.36) inhalations, respectively (P < 0.0001). No unexpected adverse events were reported. CONCLUSION: During treatment of inadequately controlled asthmatic patients with budesonide/formoterol maintenance and reliever therapy, significant improvement in patients' asthma control and reductions in asthma symptoms and as-needed medication use was observed. Patients' quality of life was improved and the treatment was well tolerated. TRIAL REGISTRATION: ClinicalTrial.gov: (NCT00939341).

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.

Pidotimod: In-depth review of current evidence.

Pidotimod, an immunostimulant, is researched for over two decades. Current evidence indicates its utility in a variety of indications in children as well as in adults. Its immunostimulant activity has been firmly established in the management of recurrent respiratory infections in children with or without asthma. Compared to standard of care alone, addition of pidotimod to standard of care significantly prevents the recurrences and reduces the severity and duration of acute episodes, ultimately resulting in reduced visits to pediatric clinics and lower absenteeism at school. In adults, pidotimod is effective in the prevention and treatment of acute infectious exacerbations of chronic bronchitis and chronic obstructive pulmonary disease (COPD). Further, it has been evaluated in indications such as pneumonia, hand-food-mouth disease, bronchiectasis, and chronic idiopathic urticaria. From a total of 32 studies conducted in child (24 studies) and adult (8 studies) population, this in-depth review discusses the current evidence of pidotimod. With further exploration, the immunostimulant activity of pidotimod might be extended to different immunological disorders.

Computed Tomography Angiography of the Extremities in Emergencies.

Computed tomography angiography (CTA) of the extremities offers a noninvasive, rapid means of evaluation of the extremities in vascular emergencies. CTA is now the first-line investigation for this purpose, offering high sensitivity and specificity in diagnosis. The learning objectives of this review article include reviewing normal arterial anatomy and variants of the upper and lower extremity, illustrating CTA findings in traumatic vascular injuries, and exploring the range of vascular pathologies that may cause acute ischemic symptoms in the extremities.

Magnetic Resonance Imaging of Musculoskeletal Emergencies.

Musculoskeletal trauma and infections are commonly encountered in the emergency department. Magnetic resonance imaging (MRI) is rarely employed in true emergencies and most musculoskeletal studies can be deferred to the outpatient setting. This article seeks to address the urgent conditions in which MRI can play a role in diagnosis, management, and treatment. This article outlines MRI's role in the evaluation of posterolateral corner injuries and other soft-tissue pathologies such as rhabdomyolysis, diabetic myonecrosis, septic arthritis, cellulitis, necrotizing fasciitis, and compartment syndrome.

Clinical Outcome of Novel H1N1 (Swine Flu)-Infected Patients During 2009 Pandemic at Tertiary Referral Hospital in Western India.

BACKGROUND: The first case of 2009 pandemic influenza A (H1N1) virus in Gujarat, India, was reported in August 2009. Oseltamivir was used for treatment of pandemic influenza in India. We discuss the clinical characteristics and outcome of the hospitalized patients with H1N1 infection during 2009 pandemic influenza season. MATERIALS AND METHODS: Hospitalized patient with laboratory-confirmed H1N1 flu during August 2009 to February 2010 were included in this retrospective study. Data were collected from hospital ICU charts. Patients discharged from hospital were considered cured from swine flu. Data analysis was performed using CDC software EPI Info v3.5.3. Both univariate and multivariate analyses were conducted. RESULTS: A total of 63 patients were included in the study, of them 41 (65%) males and 22 (35%) females. Median age was 34 (3-69) years and median duration of symptoms before hospitalization was 5 (2-20) days. Common presenting symptoms include fever 58 (92.06%), cough 58 (92.06%), breathlessness 38 (60.31%), common cold 14 (22.22%), vomiting 12 (19.04%), weakness 9 (14.28%), throat pain 7 (11.11%), body ache 5 (7.93%), and chest pain 4 (6.34%). Co-morbidities were seen in 13 (20.63%) patients. Steroids were used in 39 (61.90%) patients, and ventilatory support was required in 17 (26.98%) patients. On presentation chest x-ray was normal in 20 (31.74%) patients, while pulmonary opacities were seen in 43 (68.26%) patients. Forty-seven (74.60%) patients were cured and discharged from hospital, 14 (22.22%) patients died, and 2 (3.17%) patients were shifted to other hospital. Ventilatory requirement, pneumonia, and co-morbidities were the independent predictors of mortality, while age, sex, and steroid use were not associated with increased mortality. CONCLUSION: 2009 pandemic influenza A had the same clinical features as seasonal influenza except vomiting. Mortality rate was high in 2009 H1N1-infected patients with pneumonia, co-morbid conditions, and patients who required ventilatory support.

Evaluation of four volume-based image registration algorithms.

We evaluated 4 volume-based automatic image registration algorithms from 2 commercially available treatment planning systems (Philips Syntegra and BrainScan). The algorithms based on cross correlation (CC), local correlation (LC), normalized mutual information (NMI), and BrainScan mutual information (BSMI) were evaluated with: (1) the synthetic computed tomography (CT) images, (2) the CT and magnetic resonance (MR) phantom images, and (3) the CT and MR head image pairs from 12 patients with brain tumors. For the synthetic images, the registration results were compared with known transformation parameters, and all algorithms achieved accuracy of submillimeter in translation and subdegree in rotation. For the phantom images, the registration results were compared with those provided by frame and marker-based manual registration. For the patient images, the results were compared with anatomical landmark-based manual registration to qualitatively determine how the results were close to a clinically acceptable registration. NMI and LC outperformed CC and BSMI, with the sense of being closer to a clinically acceptable result. As for the robustness, NMI and BSMI outperformed CC and LC. A guideline of image registration in our institution was given, and final visual assessment is necessary to guarantee reasonable results.