Clinical Validation of Calf Circumference with DEXA Scans as a Measure of Muscle Mass to Assess Sarcopenia in Community Settings in Indian Postmenopausal Women.

Aims and Objective: To validate calf circumference as a reliable clinical tool for measuring muscle mass in postmenopausal women. Materials and Methods: A cross sectional study done at Ram Manohar Lohia Hospital, New Delhi from February 2023 to September 2023. Thirty postmenopausal women were enrolled for this study. Women with surgical menopause, premature ovarian failure, chronic debilitating illness and morbid obesity were excluded. In these women, muscle mass was measured using calf circumference. Also, Appendicular skeletal muscle index (ASMI), a measure of muscle mass was calculated using DEXA scan (Gold standard). The muscle mass was taken as a parameter by both methods to detect sarcopenia. The collected data was analysed and statistically evaluated to clinically validate calf circumference as a reliable tool for measuring muscle mass in Indian postmenopausal women. Results: In our study, the values at different cut offs of calf circumference was compared to ASMI scoring using gold standard investigation DEXA Scan. The better accuracy was found for the cut off point 32 cm of calf circumference with sensitivity of 100%, specificity of 60%, positive predictive value of 71.4%, negative predictive value of 100% and accuracy of 80%. The prevalence of sarcopenia was found to be 70%. Conclusion: Calf circumference can be used as reliable clinical tool to assess sarcopenia as a measure of muscle mass in Indian postmenopausal women.

STK11 Inactivation Predicts Rapid Recurrence in Inoperable Early-Stage Non-Small-Cell Lung Cancer.

PURPOSE: Molecular factors predicting relapse in early-stage non-small-cell lung cancer (ES-NSCLC) are poorly understood, especially in inoperable patients receiving radiotherapy (RT). In this study, we compared the genomic profiles of inoperable and operable ES-NSCLC. MATERIALS AND METHODS: This retrospective study included 53 patients with nonsquamous ES-NSCLC (stage I-II) treated at a single institution (University of Chicago) with surgery (ie, operable; n = 30) or RT (ie, inoperable; n = 23) who underwent tumor genomic profiling. A second cohort of ES-NSCLC treated with RT (Stanford, n = 39) was included to power clinical analyses. Prognostic gene alterations were identified and correlated with clinical variables. The primary clinical end point was the correlation of prognostic genes with the cumulative incidence of relapse, disease-free survival, and overall survival (OS) in a pooled RT cohort from the two institutions (N = 62). RESULTS: Although the surgery cohort exhibited lower rates of relapse, the RT cohort was highly enriched for somatic STK11 mutations (43% v 6.7%). Receiving supplemental oxygen (odds ratio [OR] = 5.5), 20+ pack-years of tobacco smoking (OR = 6.1), and Black race (OR = 4.3) were associated with increased frequency of STK11 mutations. In the pooled RT cohort (N = 62), STK11 mutation was strongly associated with inferior oncologic outcomes: 2-year incidence of relapse was 62% versus 20% and 2-year OS was 52% versus 85%, remaining independently prognostic on multivariable analyses (relapse: subdistribution hazard ratio = 4.0, P = .0041; disease-free survival: hazard ratio, 6.8, P = .0002; OS: hazard ratio, 6.0, P = .022). STK11 mutations were predominantly associated with distant failure, rather than local. CONCLUSION: In this cohort of ES-NSCLC, STK11 inactivation was associated with poor oncologic outcomes after RT and demonstrated a novel association with clinical hypoxia, which may underlie its correlation with medical inoperability. Further validation in larger cohorts and investigation of effective adjuvant systemic therapies may be warranted.

Effectiveness of Tibolone in Relieving Postmenopausal Symptoms for a Short-Term Period in Indian Women.

Background: Tibolone is an alternative to conventional estrogen and progesterone in relieving post-menopausal symptoms in Indian women. Material and Methods: A prospective short-term observational study was done at a tertiary care teaching hospital in New Delhi from November 2019 to September 2021. Fifty-three women, less than 60 years of age, presenting with moderate to severe intensity of menopausal symptoms as assessed by measuring menopausal rating score (MRS > 8) were enrolled and given Tibolone 2.5 mg daily for 3 months. Improvements in symptoms were seen at 1 month and 3 months. Side effects were also noted. Results: Marked improvement was seen as reduction in scores of psychological, somatic and genitourinary symptoms was noted. The psychological symptoms reduced from 8.92 ± 1.959 to 2.905 ± 1.042, the somatic symptoms decreased from 8.33 ± 2.299 to 3.4 ± 1.167, and genitourinary symptoms decreased from 3.64 ± 1.42 to 2.150 ± 0.948 after 3 months of treatment with Tibolone. Only 3 patients (5.6%) experienced vaginal spotting with no major side effects. Conclusions: Tibolone is a highly effective and well accepted drug to reduce moderate to severe menopausal symptoms, especially psychological symptoms including depression.

Correlation of Menopausal Symptoms with Serum Estradiol: A Study in Urban Indian Postmenopausal Women.

Background: Menopause is a hypoestrogenic state. Menopausal symptoms like hot flushes, depression, joint pains and urinary symptoms all correlate with falling estrogen levels. Material and Methods: Four hundred postmenopausal women who underwent natural menopause were included in the study conducted from Nov 2018 to March 2020. Surgical menopause, premature menopause and those on hormone replacement were excluded. Serum estradiol was measured and assessment of severity of menopausal symptoms was done using MRS questionnaire. MRS score of 0-4, 5-8, 9-15 and more than 16 were taken as none/minimal, mild, moderate and severe postmenopausal symptoms, respectively. Correlation between serum estradiol and symptoms was analyzed statistically. Results: Mean age of menopause in our study population was found to be 47.2 ± 3.96 years. Somatic symptoms were found maximum out of all 3 subscales in study population. Psychological subscale which included depression and mood changes was found to have the strongest correlation with serum estradiol level compared to other two subscales (somatic and genito-urinary). Discussion: Psychological symptoms, somatic symptoms and genitor urinary symptoms at menopause show correlation with falling estrogen levels. We found maximum correlation of psychological symptoms with low serum estradiol level. Conclusion: There is an inverse correlation of serum estradiol value with menopausal symptoms, with psychological symptoms (depression, anxiety, mood changes) showing highest correlation with low estrogen levels.

CDKN2A loss-of-function predicts immunotherapy resistance in non-small cell lung cancer.

Immune checkpoint blockade (ICB) improves outcomes in non-small cell lung cancer (NSCLC) though most patients progress. There are limited data regarding molecular predictors of progression. In particular, there is controversy regarding the role of CDKN2A loss-of-function (LOF) in ICB resistance. We analyzed 139 consecutive patients with advanced NSCLC who underwent NGS prior to ICB initiation to explore the association of CDKN2A LOF with clinical outcomes. 73% were PD-L1 positive (≥ 1%). 48% exhibited high TMB (≥ 10 mutations/megabase). CDKN2A LOF was present in 26% of patients and was associated with inferior PFS (multivariate hazard ratio [MVA-HR] 1.66, 95% CI 1.02-2.63, p = 0.041) and OS (MVA-HR 2.08, 95% CI 1.21-3.49, p = 0.0087) when compared to wild-type (WT) patients. These findings held in patients with high TMB (median OS, LOF vs. WT 10.5 vs. 22.3 months; p = 0.069) and PD-L1 ≥ 50% (median OS, LOF vs. WT 11.1 vs. 24.2 months; p = 0.020), as well as in an independent dataset. CDKN2A LOF vs. WT tumors were twice as likely to experience disease progression following ICB (46% vs. 21%; p = 0.021). CDKN2A LOF negatively impacts clinical outcomes in advanced NSCLC treated with ICB, even in high PD-L1 and high TMB tumors. This novel finding should be prospectively validated and presents a potential therapeutic target.

Role of Dienogest in Endometriosis in Young Women.

INTRODUCTION: Endometriosis associated pelvic pain (EAPP) is the most common complaint of patients with endometriosis. Nearly, 70% of females with endometriosis present with EAPP while endometriomas are found in 17-44% of patients. MATERIAL AND METHODS: A short-term single centre study was carried out in 56 patients in the age group of 15-35 years with complaints of pain and diagnosed as endometriosis either by imaging studies and/or by laparoscopy was given dienogest 2 mg OD, and effect of treatment was seen as improvement of pain score over a period of 3 months. The effect of dienogest was also seen on size of endometrioma. Patients were followed up at 1 and 3 months. RESULTS AND DISCUSSION: Out of 56 patients, 38 (67.8%) patients reported their pain relief within 2-5 days after starting dienogest. Out of 41 patients (73%) who had severe pain at enrollment, only 1 patient (1.79%) complained of severe pain at the end of 1 month with dienogest. Successful reduction in endometriotic cyst size (>50%) was seen in 3 patients (5.3%) at the end of 1 month with dienogest. Out of 56 patients, 41 patients (73.2%) had significant pain relief (>30%) at three months of treatment. At the end of 3 months, seven patients (12.5%) had significant cyst size reduction (>50%) with dienogest. No major side effects were noted. CONCLUSION: Dienogest is well tolerated drug for endometriosis showing significant relief of pain. However, it was seen that though endometriomas did not grow during treatment, significant regression was uncommon.

Measurement of Angle of Descent (AOD) by Transperineal Ultrasound in Labour to Predict Successful Vaginal Delivery.

INTRODUCTION: Non-progress of labour forms the largest indication caesarean section. The diagnosis of failure of descent using serial digital examination is objective, poor reproducibility, carries the risk of infection and is painful to the labouring patient. There is a need if not an alternative, adjunctive to digital vaginal examination. Measuring angle of descent (AOD) to predict vaginal birth in late labour by transperineal ultrasound provides an alternative without any of the above-mentioned drawbacks. MATERIALS AND METHODS: A prospective observational study in 64 patients in the late first stage and second stage of labour with cephalic presentation was carried out, from September 2017 to December 2018, in PGIMER and DR. RML Hospital. Angle of descent was measured by transperineal ultrasound. Angle of descent is the angle between the longitudinal axis of pubic bone and a line joining the lowest edge of the pubis to the lowest convexity of the foetal skull. Time of assessment of AOD1 was noted, and if patient did not deliver within 2 h, another AOD2 was recorded. Eighty-five readings were obtained, and AOD predicting successful vaginal delivery was calculated. RESULTS AND DISCUSSION: AOD of 116° and more resulted in vaginal delivery, spontaneous or instrumental. As the angle of descent increased, there was a decrease in time interval to vaginal delivery with correlation coefficient of - 0.939. CONCLUSION: The use of intrapartum transperineal ultrasound and measurement of angle of descent can prove to be a valuable adjunct in management of labour, especially in cases of prolonged first and second stages of labour in predicting successful vaginal delivery. AOD of 116° or more can predict successful vaginal delivery within 2 h. AOD can be used in centres having facilities of intrapartum ultrasound. The authors recommend the use of ultrasound in labour room as it is non-invasive and can provide a lot of information. This method is currently useful for tertiary centres or medical colleges.

Heart V5 predicts cardiac events in unresectable lung cancer patients undergoing chemoradiation.

BACKGROUND: Recent studies incorporating dose escalated radiation identified heart dose as a predictor of cardiac toxicity in unresectable lung cancer patients. Whether conventionally dosed radiation impacts cardiac events remains unclear. METHODS: Stage III lung cancer patients undergoing definitive chemoradiation to 60-70 Gy were analyzed. Clinical and dosimetric factors (mean heart dose, heart V5-60 in 5 Gy increments) were analyzed against freedom from ≥ grade 3 cardiac events and overall survival (OS) by log-rank test. Multivariable analysis (MVA) for factors significant on univariate analysis was performed by Cox proportional hazards. RESULTS: A total of 108 patients were identified. Median follow-up was 18.0 months. One- and two-year OS were 79% and 61%, respectively. On MVA, gross tumor volume (GTV) ≥98.6 cm3 [hazard ratio (HR): 2.11, 95% confidence interval (CI): 1.15-3.93, P=0.02] and female gender (HR: 2.01, 95% CI: 1.09-3.73, P=0.03) predicted for worse survival. Twelve patients (11%) developed ≥ grade 3 cardiac events. One- and two-year freedom from cardiac events (FFCE) was 94% and 84% respectively. On MVA, heart V5 ≥49% predicted for cardiac events (HR: 11.44, 95% CI: 1.31-111.60, P=0.03) while female gender was nearly significant (HR: 3.49, 95% CI: 0.97-16.80, P=0.06). Females presented with similar comorbidity scores, GTVs, and relapse rates but experienced higher heart doses than their male counterparts. CONCLUSIONS: Heart V5 ≥49% predicted for cardiac events after chemoradiation. However, cardiac dosimetry was not associated with survival. Rather, female gender and GTV ≥98.6 cm3 led to worse survival. This study corroborates emerging data that low-dose radiation to the heart impacts cardiac toxicity.

Effect of Endoscopic Bronchial Ultrasound on Outcomes for Stage I Non-Small-Cell Lung Cancer Patients Receiving Hypofractionated Radiotherapy.

BACKGROUND: In this study we sought to determine if staging endoscopic bronchial ultrasound (EBUS) improves outcomes in stage I non-small-cell lung cancer (NSCLC) patients who received hypofractionated radiation therapy (HFRT). PATIENTS AND METHODS: Patients with stage I NSCLC treated with HFRT from 2008 to 2015 were retrospectively identified from 3 affiliated institutions. All patients underwent positron emission tomography/computed tomography staging and a subset of patients received pretreatment EBUS. Patients with and without pre-radiation therapy EBUS were compared for baseline characteristics. The log rank test was used to compare Kaplan-Meier estimates. Univariate analysis (UVA) and multivariable analysis (MVA) were used to analyze the effect of factors on disease-free survival (DFS) and overall survival (OS). RESULTS: Ninety-two patients met study criteria. Median follow-up for the entire cohort was 21 months. Two-year DFS and OS were 63% and 81%, respectively. Two-year freedom from local, regional, and distant failure were 93%, 87%, and 87%, respectively. Thirty-seven of 92 patients (40%) received pretreatment EBUS. There were no statistically significant differences in 2-year freedom from regional failure rates, DFS, or OS for EBUS-staged versus non-EBUS-staged patients. On UVA, smaller tumor size (P = .03) and higher performance status (P = .05) were associated with improved OS. On MVA, tumor size retained significance for improved OS (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.19-0.97; P = .04) and higher performance status showed a trend toward improved OS (HR, 0.51; 95% CI, 0.23-1.11; P = .09). CONCLUSION: In this retrospective series, we did not detect a difference in regional failure or survival outcomes among stage I NSCLC patients who received invasive staging with EBUS before HFRT.