Clinical Outcomes of Immune Checkpoint Inhibitors in Unique Cohorts Underrepresented in Clinical Trials.

Regulatory approval of immune checkpoint inhibitors (ICIs) was based on results of large, randomized clinical trials, resulting in limited outcomes data in patient cohorts typically underrepresented in such trials. The objective of this study was to evaluate the efficacy and safety of ICIs in these unique patient cohorts. This is a multicenter, retrospective analysis of real-world data at six academic and community clinics in the United States from 1 January 2011 to 1 April 2018. Patients were included if they had received at least one cycle of ICI treatment. Unique patient cohorts included age > 75 years, non-White race, positive smoking history, ECOG performance status (PS) ≥ 2, BMI ≥ 30 kg/m2, autoimmune diseases (AIDs), chronic viral infections (CVI), extensive prior lines of therapy (LOTs), or >three metastatic sites. Immune-related adverse events (irAEs), overall survival (OS), and time to treatment failure were evaluated in the entire cohort and in NSCLC patients treated with PD-(L)1 monotherapy. Outcomes and their association with unique patient cohorts were compared on univariate analysis and multivariate analysis to those without a particular characteristic in the entire NSCLC PD-(L)1 monotherapy cohorts. In total, 1453 patients were included: 56.5%-smokers, 30.4%-non-White, 22.8%-elderly, 20.8%-ECOG PS ≥ 2, 15.7%-history of AIDs, and 4.7%-history of CVI. The common ICIs were nivolumab (37.1%) and pembrolizumab (22.2%). Black patients, compared to White patients, experienced fewer irAEs (OR 0.54, p < 0.001). An ECOG PS of ≥2 (HR = 2.01, p < 0.001) and an increased number of previous LOTs were associated with poor OS (the median OS of 26.2 vs. 16.2 vs. 9.6 months for one vs. two vs. three prior LOTs, p < 0.001). The above results were confirmed in anti-PD-(L)1 monotherapy non-small cell lung cancer patients (n = 384). Overall, ICIs were safe and efficacious in these typically underrepresented patient cohorts. We noted ECOG PS ≥ 2 and an increased prior LOTs were associated with poor ICI efficacy, and Black patients, compared to White patients, experienced fewer irAEs.

Transnasal endoscopic drainage of neonatal orbital abscess.

Neonatal orbital complications are rare and potentially fatal, demanding prompt diagnosis and adequate treatment. A 25-day-old neonate presented with rapidly progressive orbital complications as evidenced by proptosis, chemosis, lid oedema and restricted eye movements, developing within 3 days. There was no significant medical history or risk factors for developing infection. An initial conservative approach with antimicrobial therapy failed to show any resolve. An MRI brain, orbits and paranasal sinuses demonstrated that there were features suggestive of right orbital cellulitis with possibility of abscess formation with right ethmoidal mucoinflammatory disease and mass effect on the optic nerve causing stretching and compression by the surrounding inflammation.The patient was treated successfully with transnasal endoscopic drainage and decompression. Endoscopic access was challenging owing to the restrictive anatomy. Postoperatively, the patient showed improvement, with gradual decrease in proptosis and resolve in eye movements.

Analysis of Postural Risk and Pain Assessment in Bharatanatyam Dancers.

BACKGROUND: Bharatanatyam dance form is an amalgamation of emotion, rhythm, expression, and sculpturesque poses that demand high levels of physical and psychological power during a performance. OBJECTIVES: To explore musculoskeletal pain and analyze risk factors in Bharatanatyam dancers. The level of injury risk for the "Natyarambham" posture adopted by dancers was also assessed. MATERIALS AND METHODS: A cross-sectional study was conducted in forty female Bharatanatyam dancers who received a minimum of 5 consecutive years of formal dance training from a recognized dance institute. A self-designed questionnaire comprising of demographic profile, dancing characteristics, presence of musculoskeletal pain, and specific area of pain according to the body region was administered. The injury risk of the "Natyarambham" posture was evaluated using a rapid entire body assessment tool (REBA). RESULTS: Among 40 female dancers, 75% dancers (n = 30/40, 75% [95% CI 0.61, 0.89] reported pain. The most common site of pain was the low back (n = 22/40, 55% [95% CI 0.39, 0.71]). Using Bonferroni correction for multiple independent comparisons, a significant difference was identified between dancers with and without pain for average performances per year (P = 0.028). As per REBA risk level scoring for Natyarambham posture, 62.5% (n = 25/40, 62.5% [95% CI 0.22, 0.53]) dancers were in the category of high-risk level. CONCLUSION: The findings of this study indicated that the point prevalence of pain in Bharatanatyam dancers is high. Natyarambham posture is considered high risk based on postural assessment.

Molecular profiling of multidrug-resistant river water isolates: insights into resistance mechanism and potential inhibitors.

Polluted waters are an important reservoir for antibiotic resistance genes and multidrug-resistant bacteria. This report describes the microbial community, antibiotic resistance genes, and the genetic profile of extended spectrum ß-lactamase strains isolated from rivers at, Pune, India. ESBL-producing bacteria isolated from diverse river water catchments running through Pune City were characterized for their antibiotic resistance. The microbial community and types of genes which confer antibiotic resistance were identified followed by the isolation of antibiotic-resistant bacteria on selective media and their genome analysis. Four representative isolates were sequenced using next generation sequencing for genomic analysis. They were identified as Pseudomonas aeruginosa, Escherichia coli, and two isolates were Enterobacter cloacae. The genes associated with the multidrug efflux pumps, such as tolC, macA, macB, adeL, and rosB, were detected in the isolates. As MacAB-TolC is an ABC type efflux pump responsible for conferring resistance in bacteria to several antibiotics, potential efflux pump inhibitors were identified by molecular docking. The homology model of their MacB protein with that from Escherichia coli K12 demonstrated structural changes in different motifs of MacB. Molecular docking of reported efflux pump inhibitors revealed the highest binding affinity of compound MC207-110 against MacB. It also details the potential efflux pump inhibitors that can serve as possible drug targets in drug development and discovery.

Screening Mammography: A Pilot Study on Its Pertinence in Indian Population by Means of a Camp.

INTRODUCTION: Breast cancer incidence and related mortality is increasing in Indian women. Indian ladies hesitate to seek medical care for breast related issues. Screening mammography, proved to effectively reduce mortality, has been deemed not feasible in Indian context due to cost considerations. The suggested alternatives have not been proven to improve mortality rates. AIM: To find the relevance of screening mammography camp among Indian women. MATERIALS AND METHODS: A week long screening mammography camp was organized in a tertiary care hospital. Clinical examination was done followed by bilateral mammography. Mammograms were reported as per American College of Radiology-Breast Imaging Reporting and Data Systems (ACR-BIRADS) 5th edition specifications. Lesions deemed BIRADS 4 and 5 were biopsied. BIRADS 3 category findings were suggested short interval follow up. RESULTS: A total of 118 women, ranging from 35 to 64 years of age with mean age of 49.6 years underwent mammography. Thirty ladies with dense breast compositions further underwent sono-mammography. Six (5.1%) new cases of breast carcinomas were detected during this study and 28 (23.7%) cases with probably benign findings were advised short interval follow up. CONCLUSION: Mammography, being a proven screening modality effective in reducing mortality, needs incorporation into the nationwide program for breast cancer detection, inspite of financial considerations. Organizing mammography camps will help create awareness and encourage public to utilize services.