Limited Relationship between Cervico-Vaginal Fluid Cytokine Profiles and Cervical Shortening in Women at High Risk of Spontaneous Preterm Birth

Objective: to determine the relationship between high vaginal pro-inflammatory cytokines and cervical shortening in women at high risk of spontaneous preterm labor and to assess the influence of cervical cerclage and vaginal progesterone on this relationship. Methods: this prospective longitudinal observational study assessed 112 women with at least one previous preterm delivery between 16 and 34 weeks’ gestation. Transvaginal cervical length was measured and cervico-vaginal fluid sampled every two weeks until 28 weeks. If the cervix shortened (<25 mm) before 24 weeks’ gestation, women (cases) were randomly assigned to cerclage or progesterone and sampled weekly. Cytokine concentrations were measured in a subset of cervico-vaginal fluid samples (n = 477 from 78 women) by 11-plex fluid-phase immunoassay. Results: all 11 inflammatory cytokines investigated were detected in cervico-vaginal fluid from women at high risk of preterm birth, irrespective of later cervical shortening. At less than 24 weeks’ gestation and prior to intervention, women destined to develop a short cervix (n = 36) exhibited higher cervico-vaginal concentrations than controls (n = 42) of granulocyte-macrophage colony-stimulating factor [(GM-CSF) 16.2 fold increase, confidence interval (CI) 1.8–147; p = 0.01] and monocyte chemotactic protein-1 [(MCP-1) 4.8, CI 1.0–23.0; p = 0.05]. Other cytokines were similar between cases and controls. Progesterone treatment did not suppress cytokine concentrations. Interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor (G-CSF), interferon (IFN)-γ and tumour necrosis factor (TNF)-α concentrations were higher following randomization to cerclage versus progesterone (p<0.05). Cerclage, but not progesterone treatment, was followed by a significant increase in cervical length [mean 11.4 mm, CI 5.0–17.7; p<0.001]. Conclusions: although GM-CSF and MCP-1 cervico-vaginal fluid concentrations were raised, the majority of cervico-vaginal cytokines did not increase in association with cervical shortening. Progesterone treatment showed no significant anti-inflammation action on cytokine concentrations. Cerclage insertion was associated with an increase in the majority of inflammatory markers and cervical length

A study of drug-drug interactions in cancer patients of a south Indian tertiary care teaching hospital

Background : Drug interactions in oncology are of particular importance owing to the narrow therapeutic index and the inherent toxicity of anticancer agents. Interactions with other medications can cause small change in pharmacokinetics or pharmacodynamics of chemotherapeutic agents that could significantly alter their safety and efficacy. Aim : To identify and document the potential drug-drug interactions in prescriptions of patients receiving cancer chemotherapy. Settings and Design : A tertiary care teaching hospital based prospective study. Materials and Methods : Patients admitted in the medical oncology wards with different types of malignancies and receiving cancer chemotherapy during the period of June 2009 to November 2009 were included in the study. A detailed data collection was done in a specially designed proforma with ethical approval and consent of patients and their prescriptions were subjected to drug-drug interaction screening using Drug Interaction Fact Software Version-4 and standard references. Incidence of drug-drug interactions, their types, correlation between age, cancer type, number of drugs prescribed and incidence of drug interactions were analyzed. Statistical Analysis : Logistic regression analysis and Odds ratio were performed to identify the incidence of drug-drug interactions and their correlation with the factors above mentioned. Results : A total of 75 patients (32 males and 43 females; median age 56 years, age range 23-74) were enrolled in the study and their prescriptions were screened. 213 interactions were identified of which, 21 were major, 121 were moderate and 71 were minor. There were 13 (6.1%) clinically significant interactions between anticancer drugs and 14 (6.5%) drug-drug interactions between anticancer drugs and other drugs prescribed for co-morbidities. There was a positive correlation between number of drugs prescribed and drug interactions (P=0.011; OR 0.903). Conclusion : Though there was not any life threatening interactions, the potential interactions were brought to the oncologist purview for ensuring patients safety and to avoid undesirable effects

A study of drug-drug interactions in cancer patients of a south Indian tertiary care teaching hospital

Background: Drug interactions in oncology are of particular importance owing to the narrow therapeutic index and the inherent toxicity of anticancer agents. Interactions with other medications can cause small change in pharmacokinetics or pharmacodynamics of chemotherapeutic agents that could significantly alter their safety and efficacy. Aim: To identify and document the potential drug-drug interactions in prescriptions of patients receiving cancer chemotherapy. Settings and Design: A tertiary care teaching hospital based prospective study. Materials and Methods: Patients admitted in the medical oncology wards with different types of malignancies and receiving cancer chemotherapy during the period of June 2009 to November 2009 were included in the study. A detailed data collection was done in a specially designed proforma with ethical approval and consent of patients and their prescriptions were subjected to drug-drug interaction screening using Drug Interaction Fact Software Version-4 and standard references. Incidence of drug-drug interactions, their types, correlation between age, cancer type, number of drugs prescribed and incidence of drug interactions were analyzed. Statistical Analysis: Logistic regression analysis and Odds ratio were performed to identify the incidence of drug-drug interactions and their correlation with the factors above mentioned. Results: A total of 75 patients (32 males and 43 females; median age 56 years, age range 23-74) were enrolled in the study and their prescriptions were screened. 213 interactions were identified of which, 21 were major, 121 were moderate and 71 were minor. There were 13 (6.1%) clinically significant interactions between anticancer drugs and 14 (6.5%) drug-drug interactions between anticancer drugs and other drugs prescribed for co-morbidities. There was a positive correlation between number of drugs prescribed and drug interactions (P=0.011; OR 0.903). Conclusion: Though there was not any life threatening interactions, the potential interactions were brought to the oncologist purview for ensuring patients safety and to avoid undesirable effects

Radiographic Cortical Thickness Index Predicts Fragility Fracture in Gaucher Disease.

Background Patients with Gaucher disease (GD) have a high risk of fragility fractures. Routine evaluation of bone involvement in these patients includes radiography and repeated dual-energy x-ray absorptiometry (DXA). However, osteonecrosis and bone fracture may affect the accuracy of DXA. Purpose To assess the utility of DXA and radiographic femoral cortical thickness measurements as predictors of fragility fracture in patients with GD with long-term follow-up (up to 30 years). Materials and Methods Patients with GD age 16 years and older with a detailed medical history, at least one bone image (DXA and/or radiographs), and minimum 2 years follow-up were retrospectively identified using three merged UK-based registries (Gaucherite study, enrollment 2015-2017; Clinical Bone Registry, enrollment 2003-2006; and Mortality Registry, enrollment 1993-2019). Cortical thickness index (CTI) and canal-to-calcar ratio (CCR) were measured by two independent observers, and inter- and intraobserver reliability was calculated. The fracture-predictive value of DXA, CTI, CCR, and cutoff values were calculated using receiver operating characteristic curves. Statistical differences were assessed using univariable and multivariable analysis. Results Bone imaging in 247 patients (123 men, 124 women; baseline median age, 39 years; IQR, 27-50 years) was reviewed. The median follow-up period was 11 years (IQR, 7-19 years; range, 2-30 years). Thirty-five patients had fractures before or at first bone imaging, 23 patients had fractures after first bone imaging, and 189 patients remained fracture-free. Inter- and intraobserver reproducibility for CTI/CCR measurements was substantial (range, 0.96-0.98). In the 212 patients with no baseline fracture, CTI (cutoff, ≤0.50) predicted future fractures with higher sensitivity and specificity (area under the receiver operating characteristic curve [AUC], 0.96; 95% CI: 0.84, 0.99; sensitivity, 92%; specificity, 96%) than DXA T-score at total hip (AUC, 0.78; 95% CI: 0.51, 0.91; sensitivity, 64%; specificity, 93%), femoral neck (AUC, 0.73; 95% CI: 0.50, 0.86; sensitivity, 64%; specificity, 73%), lumbar spine (AUC, 0.69; 95% CI: 0.49, 0.82; sensitivity, 57%; specificity, 63%), and forearm (AUC, 0.78; 95% CI: 0.59, 0.89; sensitivity, 70%; specificity, 70%). Conclusion Radiographic cortical thickness index of 0.50 or less was a reliable independent predictor of fracture risk in Gaucher disease. Clinical trial registration no. NCT03240653 © RSNA, 2022 Supplemental material is available for this article.This work was supported by a Stratified Medicine Program award, Gaucherite: MR/K015338/1 from the UKRI Medical Research Council (2013-2019) and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (grant number IS-BRC-1215-20014) that in part supported SD and KP. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR or the Department of Health and Social Care