Survival outcomes of postchemotherapy retroperitoneal lymph node dissection for nonseminomatous germ cell tumors: A retrospective cohort study from a single tertiary center in South India.

Introduction: Chemotherapy, postchemotherapy retroperitoneal lymph node dissection (pcRPLND), and metastasectomy remain the standard of care for the management of advanced nonseminomatous germ cell tumor (NSGCT). Methods: We retrospectively studied 73 patients who had pcRPLND at a single tertiary-care center (2003-2022). Surgical and clinicopathological features and oncological outcomes are presented. Results: The mean age was 28.27 years (15-48). Three-fourths had Stage III disease at diagnosis. International Germ Cell Cancer Collaborative Group risk stratification was 54.54% and 21.21% in intermediate risk, and poor risk, respectively. Sixty-two patients had Standard, 7 had Salvage and 4 underwent Desperation pcRPLND. Eleven patients (15.06%) required adjunctive procedures. Thirteen patients (17.8%) had ≥ class 3 Clavien-Dindo complications and postoperative mortality occurred in 5 (6.8%) patients. The histopathologies (HPE) of the pcRPLNDs were necrosis, teratoma, and viable tumor in 39.7%, 45.2%, and 15.1%, respectively. Seven patients underwent metastasectomy. An 85% size reduction in the size of RPLN predicted necrosis. There was 71.4% concordance between pcRPLND and metastasectomy HPEs. The median follow-up was 26.72 months (inter-quartile range - 13.25-47.84). The 2-year recurrence-free survival (RFS) rate was 93% (95% confidence interval [CI]-83%-97%) and the overall survival (OS) rate was 90% (95% CI-80%-95%). This is the largest series of pcRPLND for NSGCT in India to our knowledge. Conclusion: Although most of the cohort belonged to stage III, an RFS and OS rate of >90% at 2 years was achieved. We believe that successful management of postchemotherapy residual masses in NSGCT is contingent on the availability of multidisciplinary expertise and is therefore best done at tertiary-care referral centers.

Role of squamous cell carcinoma antigen in prognostication, monitoring of treatment response, and surveillance of locally advanced cervical carcinoma.

Introduction: Squamous cell carcinoma antigen (SCC Ag) is a sub-fraction of the tumor antigen TA-4, first isolated by Kato and Torigoe, the most commonly used tumor marker in cervical cancer. It can be used as a serum marker to detect residual disease, early local recurrence, or distant metastasis in locally advanced cervical cancer even before the clinical symptoms of recurrence or metastasis. Methods and Materials: Between January 2018 and August 2018, 30 patients with squamous cell carcinoma cervix (FIGO) stages IB2-IVA, who received concurrent chemoradiation, followed by brachytherapy, were included in the study. Serum SCC Ag levels were collected at four time points during the course of the treatment, and their correlation with tumor and treatment factors were analyzed. Results: As the FIGO stage increases, mean pre-treatment SCC Ag also increases. Node-positive patients had higher pre-treatment SCC Ag as compared to those who were negative (P = 0.05). There was a statistically significant decreasing trend in the mean SCC Ag at the end of EBRT (P = 0.015). After completion of treatment, 78% had a complete response, 8% had a partial response, and 14% had progressive disease with statistically significant elevation of SCC Ag at 6 weeks of follow-up (P = 0.01). Patients who progressed or had the residual disease at follow-up were found to have high pre-treatment SCC Ag values. Conclusion: SCC Ag can be potentially used as a reference indicator of biological behavior of cervical cancer, to monitor the treatment response, and as a prognostic marker, especially in those with node-positive disease.

Randomized, Double-Blind, Active Comparator Pharmacodynamic Study of Platelet Inhibition with Crushed and Integral Formulations of Clopidogrel and Ticagrelor in Acute Coronary Syndrome.

BACKGROUND: Crushed formulations of specific antiplatelet agents produce earlier and stronger platelet inhibition. We studied the platelet inhibitory effect of crushed clopidogrel in patients with acute coronary syndrome (ACS) and its relative efficacy compared with integral clopidogrel, crushed and integral ticagrelor. OBJECTIVES: We aimed to compare the platelet inhibitory effect of crushed and integral formulations of clopidogrel and ticagrelor in patients with acute coronary syndrome (ACS). METHODS: Overall, 142 patients with suspected ACS were randomly assigned to receive crushed or integral formulations of clopidogrel or ticagrelor. Platelet inhibition at baseline and 1 and 8 h was assessed using the VerifyNow assay. High on-treatment platelet reactivity (HTPR) ≥ 235 P2Y12 reaction units (PRUs) 1 h after the medication loading dose was also determined. RESULTS: The PRU and percentage inhibition median (interquartile range) at 1 h for the different formulations were as follows: crushed clopidogrel: 196.50 (155.50, 246.50), 9.36 (- 1.79, 25.10); integral clopidogrel: 189.50 (159.00, 214.00), 2.32 (- 2.67, 19.89); crushed ticagrelor: 59.00 (10.00, 96.00), 75.53 (49.12, 95.18); and integral ticagrelor: 126.50 (50.00, 168.00), 40.56 (25.59, 78.69). There was no significant difference in PRU or percentage platelet inhibition between the crushed and integral formulations of clopidogrel (p = 0.990, p = 0.479); both formulations of ticagrelor were superior to the clopidogrel formulations (p < 0.05). On paired comparison, crushed ticagrelor showed robust early inhibition of platelets compared with the integral formulation (p = 0.03). Crushed clopidogrel exhibited the maximal HTPR of 34.3%, but was < 3% for both formulations of ticagrelor. CONCLUSIONS: The platelet inhibitory effect of crushed clopidogrel is not superior to integral preparation in patients with ACS. Crushed ticagrelor produced maximal platelet inhibition acutely. HTPR rates in ACS are similar and very low with both formulations of ticagrelor, and maximal with crushed clopidogrel. Clinical Trials Registry of India identifier number CTRI/2020/06/025647.

Distinct opposing associations of upper and lower body fat depots with metabolic and cardiovascular disease risk markers.

BACKGROUND: To examine the associations of total and regional adiposity with metabolic and cardiovascular disease (CVD) risk markers. METHODS: This cross-sectional study included 1080 (53.8% men, aged 39-44 years) individuals from South India. Anthropometry (height, weight, waist and hip circumference), body composition assessment using dual-energy X-ray absorptiometry (DXA), blood pressure (BP), and plasma glucose, insulin and lipids were measured. Regression analysis was used to examine associations of standardized fat measurements with type 2 diabetes (T2D), insulin resistance (IR), hypertension and hypertriglyceridemia and continuous measurements of BP, glucose, insulin, HOMA-IR and lipids. Contour plots were constructed to visualize the differential effect of upper and lower fat depots. RESULTS: DXA-measured fat depots were positively associated with metabolic and CVD risk markers. After adjusting for fat mass index, upper body fat remained positively, while lower body fat was negatively associated with risk markers. A one standard deviation (SD) increase in android fat showed higher odds ratios (ORs) for T2D (6.59; 95% CI 3.17, 13.70), IR (4.68; 95% CI 2.31, 9.50), hypertension (2.57; 95% CI 1.56, 4.25) and hypertriglyceridemia (6.39; 95% CI 3.46, 11.90) in men. A 1 SD increase in leg fat showed a protective effect with ORs for T2D (0.42; 95% CI 0.24, 0.74), IR (0.31; 95% CI 0.17, 0.57) and hypertriglyceridemia (0.61; 95% CI 0.38, 0.98). The magnitude of the effect was greater with DXA-measured fat compared with anthropometry. CONCLUSION: At any level of total body fat, upper and lower body fat depots demonstrate opposite risk associations with metabolic and CVD risk markers in Asian Indians.

MODELLING THE RISK FACTORS FOR BIRTH WEIGHT IN TWIN GESTATIONS: A QUANTILE REGRESSION APPROACH.

Birth weight is used as a proxy for the general health condition of newborns. Low birth weight leads to adverse events and its effects on child growth are both short- and long-term. Low birth weight babies are more common in twin gestations. The aim of this study was to assess the effects of maternal and socio-demographic risk factors at various quantiles of the birth weight distribution for twin gestations using quantile regression, a robust semi-parametric technique. Birth records of multiple pregnancies from between 1991 and 2005 were identified retrospectively from the birth registry of the Christian Medical College and hospitals in Vellore, India. A total of 1304 twin pregnancies were included in the analysis. Demographic and clinical characteristics of the mothers were analysed. The mean gestational age of the twins was 36 weeks with 51% having preterm labour. As expected, the examined risk factors showed different effects at different parts of the birth weight distribution. Gestational age, chroniocity, gravida and child's sex had significant effects in all quantiles. Interestingly, mother's age had no significant effect at any part of the birth weight distribution, but both maternal and paternal education had huge impacts in the lower quantiles (10th and 25th), which were underestimated by the ordinary least squares (OLS) estimates. The study shows that quantile regression is a useful method for risk factor analysis and the exploration of the differential effects of covariates on an outcome, and exposes how OLS estimates underestimate and overestimate the effects of risk factors at different parts of the birth weight distribution.

Predictive Value of Serum Myoglobin and Creatine Phosphokinase for Development of Acute Kidney Injury in Traumatic Rhabdomyolysis.

INTRODUCTION: Rhabdomyolysis (RM) is a condition where there is injury to striated muscle fibers causing release of myoglobin, creatine phosphokinase (CPK), and other intracellular contents into the circulation. High myoglobin levels cause acute kidney injury (AKI). Trauma is the most common cause of RM and development of complications related to the degree of myoglobin released. Currently, the degree of RM is assessed and treatment is instituted based on serum CPK. As myoglobin is the direct cause of AKI, we set out to determine if serum myoglobin is a more reliable predictor than CPK for the development of AKI in traumatic RM. METHODOLOGY: A prospective observational study of 90 patients was admitted to the surgical Intensive Care Unit/high dependency unit of a tertiary hospital with traumatic RM whose serum CPK >5000 U/L. Along with standard treatment including intravascular volume optimization and hemodynamic stabilization, they were treated with "crush protocol." Daily/twice a day, serum CPK and myoglobin were estimated. Categorical data are expressed as frequency and percentage, and the continuous variables are presented as mean (standard deviation) or median (interquartile range) based on normality. Other statistical analyses were done using the Chi-square test, independent t-test, and rank sum test based on normality. RESULTS: Fourteen out of 90 patients developed AKI and one patient required renal replacement therapy. CPK value of >12,000 U/l was identified to have 64% sensitivity and 56% specificity for developing AKI whereas serum myoglobin value of >5000 ng/ml was identified to have 78% sensitivity and 77% specificity for developing AKI. CONCLUSION: Following traumatic RM, in patients on "crush protocol," serum myoglobin is a more sensitive and specific test than serum CPK, for predicting AKI.

The role of vitamin D in post-thyroidectomy hypocalcemia: Still an enigma.

BACKGROUND: There is conflicting evidence regarding the role of vitamin D deficiency in the development of post-thyroidectomy hypocalcemia. Recent reports show postoperative parathormone (PTH) is unreliable in predicting post-thyroidectomy hypocalcemia in vitamin D deficient patients. We conducted this study to analyze the role of vitamin D status in the development of post-thyroidectomy hypocalcemia and to evaluate its effect on the predictability of PTH as a marker for post-thyroidectomy hypocalcemia. METHOD: A retrospective review of prospectively collected data of patients undergoing thyroidectomy between August 2007 to September 2013 (n = 150) was performed. Results of preoperative calcium, albumin, vitamin D, PTH and postoperative calcium, albumin, and PTH were collated. Patients were divided into 2 groups based on their vitamin D status: group A, vitamin D ≥ 20 ng/mL and group B, vitamin D < 20 ng/mL. RESULTS: Vitamin D deficiency was present in 80 (53.3%) patients and post-thyroidectomy hypocalcemia developed in 67 (44.7%). The incidence of postoperative hypocalcemia was similar in both the groups (48.6% and 41.3%, respectively). Vitamin D status was not associated with the development of post-thyroidectomy hypocalcemia (P = .23). Postoperative PTH of <8 pg/mL was strongly associated with the development of hypocalcemia in both the groups (P = .0002 and .0045, respectively). The area under the receiver operator characteristic curve in group B (0.68) was less than in group A (0.76; P = .41). CONCLUSION: The majority of patients were vitamin D deficient in this cohort, but this did not increase the risk of post-thyroidectomy hypocalcemia, nor did it interfere with the predictability of PTH as a marker of post-thyroidectomy hypocalcemia.