Prognostic role of soluble ST2 in acute coronary syndrome with diabetes.

BACKGROUND: Acute coronary syndrome (ACS) patients are at an increased risk of major adverse cardiovascular events (MACE). The objective of our study was to assess whether cardiac biomarker like soluble ST2 (sST2) can predict MACE among ACS patients with diabetes. MATERIALS AND METHODS: A total of 122 patients with ACS were included in the study. sST2 level in blood plasma samples was quantified using enzyme-linked immunosorbent assay (ELISA). Prognostic utility of sST2 for the primary outcome of MACE which included mortality, rehospitalization due to chest pain, unstable angina, recurrent myocardial infarction (MI) and stroke, was assessed during follow-up. RESULTS: The median follow-up period was of 180 days. ROC (receiver operating characteristic) curve demonstrated that elevated levels of sST2 were able to predict mortality, and MACE in ACS patients, along with increased risk of occurrence of MACE and mortality in ACS patients having diabetes. Kaplan-Meier plots revealed a significant increase in the occurrence of MACE in diabetic ACS patients (P = 0.006; by log-rank test). Cox regression analysis revealed that sST2 is not an independent predictor of mortality and MACE in ACS patients having diabetes; however, high sST2 level was found to be a predictor of MACE in all ACS subjects in the fully adjusted model with a hazard ratio (HR) of 5.8 (P = 0.032). CONCLUSION: The current study indicates that elevated levels of sST2 might be a suitable biomarker to evaluate the risk of future adverse cardiovascular events in ACS patients with diabetes.

End points in heart failure-are we doing it right?

PURPOSE: Heart Failure (HF) continues to be associated with high mortality and morbidity. We attempted to identify the most common end points used in phase 3 clinical trials of heart failure and discuss their merits and demerits. METHODS: Literature evaluation was done using the databases PubMed and Clinicaltrials.gov from January 2010 to December 2016 to identify randomised clinical trials (RCTs) evaluating the effect of therapeutic drugs on heart failure. Following the literature search, the data on the primary end points were extracted from each of the selected trials. The most recurrent and important end points of Phase III clinical trials for HF over the last six years were identified for further discussion. RESULTS: From our search, it was observed that the most common end points used in trials with acute heart failure (AHF) were composite end point, dyspnea, CV death and most common end points used in trials with chronic heart failure (CHF) were composite end point, 6 minute walk test (6MWT), CV death or HFH, Vo2 max, all cause mortality, left ventricular ejection fraction (LVEF), and dyspnea. CONCLUSION: Choosing the appropriate end points is a critical step in the study design that could turn the tide in the beleaguered drug development pipeline of HF, resulting in the right molecule reaching the HF community.

Prognostic Factors and Outcomes of Early-Stage Hodgkin's Lymphoma: Multi-Institutional Data From South India.

Early-stage Hodgkin's lymphoma (ESHL) is highly curable, usually with a combination of chemotherapy and radiation. Real-world data may show differences in survival and prognostic factors when compared to clinical trials. There is limited published literature on ESHL from India. The data on the baseline characters, treatment, and outcomes of patients with ESHL (stage IA, IB, and IIA) were obtained from five institutions' medical records and entered in a common database. Event-free survival (EFS) and overall survival (OS) were estimated using the Kaplan Meier method, and cox-regression analysis was used to identify prognostic factors. There were 258 patients [median age was 37 (18-75) years; [males:160 (62%); stage I: 41%; B symptoms: 17 (6%); bulky disease:19 (15%)] treated between 2000 and 2020 who were evaluable. The common chemotherapies used were ABVD [N = 180 (70%)], COPP-ABVD hybrid [N = 52 (21%)], and COPP [N = 14 (5%)]. Median number of cycles were 4 (2-8) and 93 (47%) received radiation at end of treatment. After a median follow-up of 60 months, the 5 years EFS was 87% and OS was 92%. On multivariate analysis, the following factors adversely affected the EFS: Male gender [hazard ratio (HR) = 2.23, P = 0.02] and Hemoglobin < 10.5g/dL [hazard ration (HR) = 2.20, P = 0.02], and the following adversely affected the OS: Hemoglobin < 10.5g/dL [hazard ratio (HR) = 4.05, P = 0.001], Male gender [hazard ratio (HR) = 3.59, P = 0.004], Stage 2 [hazard ratio (HR) = 2.65, P = 0.002] and ECOG PS (2-3) [hazard ratio (HR) = 3.35, P = 0.01]. Using the hemoglobin, stage and gender a 3-item prognostic score could identify patients with very good outcomes (score 0; 5 years OS:100%) and poor outcomes (score 3; 5 years OS; 49%). This is one of the first multi-center real-world data exclusively focusing on ESHL from India. Though the survival of the entire population was good, there are subsets of patients who have poor outcomes, which may be identified using simple parameters. These parameters need validation in a larger dataset. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01692-9.

Cost-effectiveness of response-adapted therapy (RAT) for advanced Hodgkin's Lymphoma compared with conventional treatment in India: a Markov-model based analysis.

Cost effectiveness analysis of interim positron emission tomography (PET-2, done after 2 cycles of chemotherapy) based response adaptive therapy (RAT) approaches in advanced Hodgkin lymphoma (aHL) are not available from an Indian perspective. We used a five-year decision analytics model to assess the cost-effectiveness of the two RAT approaches [(escalation (RAT-1) or de-escalation (RAT-2)] compared with standard care (SOC) in aHL (mean age:35 years). Modelling data was derived from secondary sources and sensitivity analyses were performed to assess the robustness of the model. Net monetary benefit (NMB) gained from RAT2 in Indian rupees (INR) (INR 2,26,896) was higher than the RAT1 (INR 1,83,138) when compared with SOC. Proportion achieving the complete response after initial treatment (CR1) was the key determining factor for the RAT1/2 dominance over SOC. Despite higher initial input costs, response-adapted therapy of aHL was cost-effective by minimizing the cost incurred and disutility experienced during relapse and salvage.

Despite higher initial costs, response-adapted therapy based on the interim PET scan after 2 cycles of chemotherapy was more cost-effective when compared to standard therapy with 6 cycles of ABVD in patients with advanced Hodgkin's lymphoma. Among the RAT approaches, de-escalation (RAT-2) had better cost-effectiveness than the escalation approach (RAT-1).

Randomized Double-Blind Placebo-Controlled Study of Olanzapine for Chemotherapy-Related Anorexia in Patients With Locally Advanced or Metastatic Gastric, Hepatopancreaticobiliary, and Lung Cancer.

PURPOSE: Anorexia occurs in 30%-80% of patients with advanced malignancies, which may be worsened with chemotherapy. This trial assessed the efficacy of olanzapine in stimulating appetite and improving weight gain in patients receiving chemotherapy. METHODS: Adults (≥18 years) with untreated, locally advanced, or metastatic gastric, hepatopancreaticobiliary (HPB), and lung cancers were randomly assigned (double-blind) to receive olanzapine (2.5 mg once a day for 12 weeks) or placebo along with chemotherapy. Both groups received standard nutritional assessment and dietary advice. The primary outcomes were the proportion of patients with weight gain > 5% and the improvement in appetite (assessed by the visual analog scale [VAS] and the Functional Assessment of Chronic Illness Therapy system of Quality-of-Life questionnaires Anorexia Cachexia subscale [FAACT ACS]). Secondary end points were change in nutritional status, quality of life (QOL), and chemotherapy toxicity. RESULTS: We enrolled 124 patients (olanzapine, 63 and placebo, 61) with a median age of 55 years (18-78 years), of whom 112 (olanzapine, 58 and placebo, 54) were analyzable. The majority (n = 99, 80%) had metastatic cancer (gastric [n = 68, 55%] > lung [n = 43, 35%] > HPB [n = 13, 10%]). The olanzapine arm had a greater proportion of patients with a weight gain of > 5% (35 of 58 [60%] v 5 of 54 [9%], P < .001) and improvement in appetite by VAS (25 of 58 [43%] v 7 of 54 [13%], P < .001) and by FAACT ACS (scores ≥37:13 of 58 [22%] v 2 of 54 [4%], P = .004). Patients on olanzapine had better QOL, nutritional status, and lesser chemotoxicity. Side effects attributable to olanzapine were minimal. CONCLUSION: Low-dose, daily olanzapine is a simple, inexpensive, well-tolerated intervention that significantly improves appetite and weight gain in newly diagnosed patients on chemotherapy.

Use of "Repurposed" Drugs in the Treatment of Epithelial Ovarian Cancer: A Systematic Review.

Epithelial ovarian cancer has poor outcomes with standard therapy and limited options for treatment of recurrent disease. This systematic review summarizes the data on the clinical use of repurposed drugs. We searched for clinical studies using "repurposed" agents for the treatment of ovarian cancer in the following databases: PubMed, clinicaltrials.gov, Clinical Trial Registry of India, European Clinical Trials Registry, and Chinese Clinical Trial Registry. We excluded reviews, preclinical studies, and non-English language studies. We assessed the quality of included studies. The following agents/class of agents were included: statins, hydroxychloroquine, metformin, itraconazole, nonsteroidal anti-inflammatory drugs, vitamin D, proton pump inhibitors, beta-blockers, and sodium valproate. Only one randomized controlled trial investigated metformin, which found no benefit of metformin. However, this had a high risk of bias (no details of randomization). Among the observational studies, 70% were of high quality (Newcastle-Ottawa scale ≥7). Clinical benefit was seen for itraconazole, beta-blockers, metformin, statins, and proton pump inhibitors. Though multiple studies aim to repurpose agents in epithelial ovarian cancer, the most published literature is observational, and none are practice-changing. Given the solid preclinical data regarding the anticancer efficacy of these agents, well-designed clinical trials are urgently required.

Phase II study of sodium valproate in combination with oral etoposide in platinum-resistant ovarian cancer.

Patients with platinum-resistant ovarian cancer (PROC) have limited therapeutic options and poor survival. There is a need for the development of newer therapies. Sodium valproic acid (VPA) is a short-chain fatty acid histone deacetylase (HDAC) inhibitor with antitumor activity in preclinical models of PROC. Synergism with conventional cytotoxic agents like etoposide has been demonstrated. In this prospective, single-arm, open-label, phase 2 study, we included patients ≥ 18 years with histologically or cytologically confirmed PROC and Eastern Cooperative Oncology Group performance status (ECOG-PS) 0-3. Patients received oral VPA 60 mg/kg/day in three divided doses for 3 days (D1-D3), followed by oral etoposide 50 mg once daily for two consecutive weeks (D4-D17). Serum samples were collected to assess peak VPA drug levels. The primary endpoint was the overall response rate (ORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. We sought to show an improvement in response rate from 25% (historically with oral etoposide) to 40% with the addition of VPA. 27 patients were enrolled in the study, and 18 [median age: 52 (45-59) years; serous histology:17 (94%); ECOG-PS 2 or 3: 14 (78%)] were evaluable for the response after 4 months. Nine patients were lost from follow-up before achieving the primary endpoint (mainly due to Covid-related lockdown issues). The median number of prior lines of treatment was 2 (1-3). ORR was 0% according to GCIG criteria. The disease was stable in two patients [clinical benefit rate (CBR) of 11%]. The median OS and PFS were 7 months and 2 months, respectively. Grade ≥ 3 adverse events were reported in 6 (33%) patients. The addition of valproic acid to oral etoposide in patients with PROC and poor general condition was not helpful and failed to improve responses compared to those historically achieved with single-agent etoposide. However, further phase 2 randomized controlled trials with larger sample size can be done to confirm the findings.

Long Term Prognostic Utility of Matrix Metalloproteinase-9 in Patients with Acute Coronary Syndrome - A Systematic Review.

BACKGROUND: Acute Coronary Syndrome (ACS) is the leading cause of morbidity and mortality in developed countries. Numerous groups have explored single and multiple biomarker strategies to identify diagnostic prognosticators of ACS, which will improve our ability to identify high-risk individuals. Matrix Metalloproteinase (MMP-9) is one potential biomarker, which has been widely studied in ACS. Recent reports have showed the prognostic utility of MMP-9, but due to inconsistent results, it has not been possible to draw firm conclusions. OBJECTIVE: This review aims to explore the ability of MMP-9 to predict the long-term prognosis of ACS. To clarify this issue, we conducted a literature review to provide a comprehensive assessment of MMP-9 levels in ACS patients. METHODS: We retrieved a total of 1501 articles from PubMed and Google Scholar. After thorough scrutiny, 12 original research articles were found fulfilling the inclusion-exclusion criteria. MMP-9's ability as a biomarker of prognostication post ACS was reviewed. PRISMA guidelines were used for reporting. RESULTS: The results revealed that MMP-9, apart from being an efficient diagnostic biomarker for ACS, helps in predicting the future risk of ACS with disease outcome. A positive correlation was found between plasma MMP-9 and left ventricular remodeling. A positive association was also found between cardiovascular death and higher MMP-9 levels. CONCLUSION: MMP-9 can be a potential prognostic marker for ACS and aids in identifying high-risk patients for intensive management during follow -up.

A Simple, Novel Prognostic Score in Platinum Sensitive Relapsed Ovarian Cancer.

OBJECTIVES: Epithelial ovarian cancer is one of the commonest gynecologic cancers and one with the highest mortality. This retrospective cohort study was done to identify predictors of outcomes in platinum-sensitive relapsed ovarian cancer patients (PS-ROC). METHODS: Data regarding baseline characters, laboratory findings, therapeutic details and survival outcomes was obtained from the medical records of PS-ROC patients presented between January 2015 and December 2019. Prognostic score was constructed using factors which were significant on multivariate analysis to predict survival outcomes. RESULTS: A total of 71 (PS-ROC) patients were included in the study with a median age of 50 years. Relapse treatment was either chemotherapy alone (n=53, 75%) or chemotherapy plus surgery (n=18, 25%). The estimated progression-free survival (PFS) and overall survival were 10 and 29 months, respectively. The overall response rate after treatment of relapse was 59%. Prognostic score was created with the 3 factors (each scoring 1 point) which were predictive of PFS (higher lymphocyte-monocyte ratio, longer platinum-free interval and secondary cytoreduction). Patients with low score (0,1) had better PFS than those with higher score (2,3) (13 vs. 7 mo [P=0.0001]). CONCLUSIONS: A composite prognostic score could predict outcomes in PS-ROC and potentially identify a subgroup with very poor prognosis. Future studies with a greater number of patients are needed to validate these findings. This information could help tailor more intense therapies to the high-risk patients and attempt to improve outcomes and serve as stratification factors for prospective trials.

The "collateral damage" of the war on COVID-19: impact of the pandemic on the care of epithelial ovarian cancer.

The covid-19 pandemic has impacted the management of non-covid-19 illnesses. Epithelial ovarian cancer (EOC) requires long-duration multidisciplinary treatment. Teleconsultation and shared care are suggested solutions to mitigate the consequences of the pandemic. However, these may be challenging to implement among patients who come from the lower economic strata. We report the disastrous impact of the pandemic on the care of EOC by comparing patients who were treated during the pandemic with those treated in the previous year. We collected the following data from newly diagnosed patients with EOC: time from diagnosis to treatment, time for completion of planned chemotherapy, and proportion of patients completing various components of therapy (surgery and chemotherapy). Patients treated between January 2019 and September 2019 (Group 1: Pre-covid) were compared with those treated between January 2020 and December 2020 (Group 2: During covid pandemic). A total of 82 patients were registered [Group 1: 43(51%) Group 2: 39(49)]. The median time from diagnosis to start of treatment was longer in group 2 when compared to group 1 [31(23-58) days versus 17(11-30) days (p = 0.03)]. The proportion of patients who had surgery in group 2 was lower in comparison to group 1 [33(77%) versus 21(54%) (p = 0.02)]. Proportion of patients who underwent neoadjuvant (NACT) and surgery were fewer in group 2 in comparison to group 1 [9(33%) versus 18(64%) p = 0.002]. Among patients planned for adjuvant chemotherapy, the median time from diagnosis to treatment was longer in group 2 [28(17-45) days, group 1 versus 49(26-78) days, group 2 (p = 0.04)]. The treatment of patients with EOC was adversely impacted due to the COVID-19 pandemic. There was a compromise in the proportion of patients completing planned therapy. Even among those who completed the treatment, there were considerable delays when compared with the pre-covid period. The impact of these compromises on the outcomes will be known with longer follow-up.

Assessment of Peripheral Blood Mononuclear Cells Senescence and Endothelial Dysfunction among Adults with High Cardiovascular Risk. / Avaliação da Senescência de Células Sanguíneas Mononucleares Periféricas e na Disfunção Endotelial entre Adultos com Alto Risco Cardiovascular.

BACKGROUND: Cardiovascular diseases (CVD) are one of the leading causes of mortality and morbidity worldwide. Biological aging has been associated with the occurrence of adverse cardiovascular outcomes; however, the underlying mechanism of this process remains unknown. OBJECTIVES: This study sought to evaluate if peripheral blood mononuclear cell (PBMC) senescence and endothelial biomarkers could influence cardiovascular (CV) risk and be suitable markers for the early detection of cardiovascular diseases in adults. METHODS: In this cross-sectional study patients free of CVD were classified as lower (n=32) and higher Interheart Risk (IHR) scores (n=28). PBMC senescence was assessed by estimating the telomerase activity (TA) and detecting the presence of senescent cells and endothelial dysfunction by estimating the concentration of nitrite and nitrate and of total antioxidant capacity (TAC). Statistical analysis was performed with SPSS version 16.0 (SPSS Inc., Chicago, IL). All p-values <0.05 were considered statistically significant. RESULTS: PBMC senescence 0.95 [p-value = 0.0001; 95% CI (0.874-1.026)] was a significant predictor of patients with higher IHR scores with a cut-off value of 21.65 with a sensitivity and specificity of 92% and 88% respectively. PBMC senescence, nitrite and nitrate and TA were found to be independently associated with high IHR scores. CONCLUSION: PBMC senescence, TA and nitrite, and nitrate status are suitable measures to predict high cardiovascular risk in adults with CV risk. Nevertheless, long-term follow-up studies are needed to confirm these findings. (Arq Bras Cardiol. 2021; 116(1):37-47).

FUNDAMENTO: Doenças cardiovasculares (DCV) são uma das principais causas de mortalidade e morbidade em todo o mundo. O envelhecimento biológico tem sido associado à ocorrência de resultados cardiovasculares. Entretanto, o mecanismo subjacente desse processo ainda é desconhecido. OBJETIVOS: Buscamos avaliar se a senescência das células sanguíneas mononucleares periféricas (CSMP) e biomarcadores endoteliais poderiam influenciar o risco cardiovascular (CV) e ser marcadores adequados para a detecção precoce de doenças cardiovasculares em adultos. MÉTODOS: Neste estudo transversal, pacientes livres de DCV foram classificados como baixo (n=32) e alto (n=28) escore de risco intracardaco (IHR) A senescência das CSMP foi avaliada estimando-se a atividade de telomerase (AT) e detectando-se a presença de células senescentes e disfunção endotelial, estimando-se a concentração de nitrito e nitrato e a capacidade antioxidante total (CAT). A análise estatística foi realizada com o software SPSS, versão 16.0 (SPSS Inc., Chicago, IL). Todos os p-valores <0,05 foram considerados estatisticamente significativos. RESULTADOS: A senescência de CSMP de 0,95 [p-valor = 0,0001; 95% IC (0,874-1,026)] foi um indicador significativo de pacientes com escore de IHR mais alto, com um valor de corte de 21,65, com sensibilidade e especificidade de 92% e 88% respectivamente. Identificou-se que a senescência de CSMP, nitrito e nitrato, e AT eram independentemente associadas a um escore de IHR alto. CONCLUSÃO: Os status de nitrito e nitrato e AT, e a senescência de CSMP são medidas adequadas para prever o alto risco cardiovascular em adultos com risco CV. Entretanto devem ser realizados estudos de acompanhamento de longo prazo para confirmar esses achados. (Arq Bras Cardiol. 2021; 116(1):37-47).

Factors which Influence the Levels of ST-2, Galectin-3 and MMP-9 in Acute Coronary Syndrome.

BACKGROUND: Several cardiac biomarkers are being studied to explore their potential in the prognostication of Acute Coronary Syndrome (ACS). However, there are limited studies exploring the relationship between these biomarkers and clinical, laboratory and demographic characteristics. OBJECTIVE: We sought to determine the factors which influence the concentration of novel cardiac biomarkers such as Galectin-3, suppression of tumorigenicity-2 (ST-2) and Matrix Metallopeptidase-9 (MMP-9) in patients with ACS. METHODS: A total of 122 patients with ACS were enrolled in the study. The study patients were categorized into two groups namely: STEMI (n=58) and NSTEMI/UA (n=64). Plasma samples were used to determine the level of biomarkers, Galectin-3 and ST-2, and serum samples were used to determine the levels of MMP-9 using the Enzyme-linked immunosorbent assay (ELISA). The association between the plasma and serum levels of biomarkers and, demographic, clinical and laboratory variables were determined. Statistical analyses for the study were performed using SPSS 16.0 software (SPSS Inc., Chicago, IL, USA). RESULTS: Elderly aged [0.107 (0.012-0.969); p=0.047] patients had higher ST-2. Galectin-3 was higher among female patients [3.693(1.253-10.887); p=0.018] and patients with low left ventricular ejection fraction [2.882 (1.041-7.978); p=0.042]. Patients with lower body mass index [3.385 (1.241-9.231); p=0.017], diabetes [3.650 (1.302-10.237); p=0.014] and high total leukocyte count [2.900 (1.114-7.551; p=0.029] had higher MMP-9 levels. CONCLUSION: The concentration of galectin-3, ST-2 and MMP-9 are independently influenced by demographic, clinical and laboratory characteristics. It is estimated that these factors should be accounted for when interpreting the results of the biomarker assays.

The Ascent of Mineralocorticoid Receptor Antagonists in Diabetic Nephropathy.

Diabetic nephropathy is defined as a decline in the renal function and an increase in the amount of albuminuria (>300 mg/day). The interruption of the renin-angiotensin-aldosterone system (RAAS) by well-established therapies such as angiotensin-converting enzyme inhibitor, angiotensin receptor blockers, calcium channel blockers or diuretics has been beneficial in reducing the progression of renal diseases; however, there is an increase in the levels of aldosterone due to the aldosterone escape phenomenon. Newer and novel approaches to counteract this aldosterone breakthrough while accentuating the anti-hypertensive and anti-proteinuric effects of these agents would be ideal and mineralocorticoid receptor antagonists fit in this slot perfectly. This review attempted to evaluate the safety and efficacy of and mineralocorticoid receptor antagonists for diabetic nephropathy. Presently mineralocorticoid receptor antagonists such as spironolactone, eplerenone and finerenone are being investigated as both monotherapies and as additional therapies. Clinical studies have shown that these drugs have been effective in the reduction of blood pressure, urinaryalbumin- excretion and estimated glomerular filtration rate. The commonly observed adverse effects are hyperkalemia, gynaecomastia and vaginal bleeding, that are bothersome with spironolactone seems to be avoidable if these patients are switched to non-steroidal and mineralocorticoid receptor antagonists such as finerenone and eplerenone. Most of the studies have only evaluated the shortterm effects of mineralocorticoid receptor antagonists on diabetic nephropathy. Hard outcomes such as cardiovascular events, creatinine doubling, progression to end-stage renal disease, mortality and the need for temporary or permanent dialysis need to be studied with these molecules.

The assessment of the quality of randomized controlled trials published in Indian medical journals.

AIM: In this retrospective cross-sectional study, we sought to evaluate if the published randomized controlled trials (RCTs) reported in the year 2017 among the Indian medical journals (IMJs) complied with the Consolidated Standards of Reporting Trials (CONSORT) guidelines and identify domains where reporting could be improved. METHODS: A literature search was performed using PubMed and Google Scholar to identify all the IMJs that published RCTs in the year 2017. In the archives of the identified journals, the number of published RCTs was identified and the full text was obtained. We selected articles that stated RCT in abstract and title and that evaluated the safety and efficacy of all therapeutic and preventive interventions. RESULTS: A total of seven IMJs comprising of the Indian Journal of Anesthesia, Indian Journal of Dermatology, Venereology and Leprology, Indian Journal of Pharmacology, Indian Journal of Ophthalmology, Journal of Obstetrics and Gynaecology, Journal of Pharmacology and Pharmacotherapeutics, and Indian Journal of Medical and Pediatric Oncology that published a total of 84 RCTs were included. The mean compliance score of all the RCTs was 13.7 ± 2.66 (57%). Most RCTs had serious reporting deficiencies in the methodology and result sections. DISCUSSION: In spite of journals making it mandatory for prospective authors to comply with the CONSORT guidelines, it is intriguing that there continues to be significant lacunae in reporting RCTs adequately in most IMJs. CONCLUSION: There is an urgent need to impart training to the medical community of our country in clinical research methods and reporting of RCTs.

A peek into the drug development scenario of endometriosis - A systematic review.

PURPOSE AND OBJECTIVE: Endometriosis is a gynaecological disease that is characterised by the presence of endometrium like tissue-epithelium and stroma that develops outside the uterine cavity, which is responsible for pelvic pain and infertility. Even though several medical therapies exist for the treatment of endometriosis, each of the drug class has its own limitations such as cost of treatment, side-effects and its short-term effect on the symptoms of endometriosis. In this review, we have attempted to summarize the current status and challenges of drug development for endometriosis. METHODS: A systematic review was done and all the RCTs were selected from the identified hits. We included studies that explored the usage of therapeutic drugs on endometriosis patients from inception till November 2016. The search term used was 'Endometriosis' using PubMed and Clinicaltrials.gov. For the final analysis, 60 articles were analyzed and we identified the newly emerging drug therapies for endometriosis treatment and have briefed their current status and challenges in drug development for endometriosis. The quality of the selected studies was assessed based on the degree of bias. RESULTS: The current classes of drugs that have shown promising therapeutic results include Gonadotropin- releasing hormone (GnRH) antagonists, aromatase inhibitors (AI), and selective progesterone and estrogen receptor modulators, dopamine receptor-2-agonists and statins. The drugs that failed midway during development include tanezumab, rosiglitazone, infliximab, pentoxifylline, telapristone acetate, asoprisnil and raloxifene. CONCLUSION: From the literature review, it appears that the most promising molecules for the treatment of endometriosis in the near future include elagolix, mifepristone, TAK-385, KLH-2109 and ASP1707 and cabergoline. It remains to be seen if these molecules would succeed large phase 3 clinical trials and overcome the regulatory hurdles to become an essential tool in the gynaecologist's armamentarium against endometriosis.

Do ANGPTL-4 and galectin-3 reflect the severity of coronary artery disease?

BACKGROUND: Coronary artery disease (CAD) is one of the leading causes of mortality and morbidity worldwide. We thereby sought to investigate whether the biomarkers, angiopoietin-like 4 (ANGPTL-4) and galectin-3, reflect the severity of CAD. METHODS: Patients were screened based on inclusion/exclusion criteria and written informed consent was obtained from the patients. Serum ANGPTL-4 and galectin-3 was quantified using enzyme-linked immunosorbent assay (ELISA) and correlated with the Global Registry of Acute Coronary Events (GRACE) and GENSINI score using Spearman's rank correlation coefficient and multivariate analysis. RESULTS: A total of 226 patients consisting of ST-segment elevation myocardial infarction (STEMI), non-STEMI/unstable angina (USA), chronic stable angina (CSA) and normal controls (NCs) participated in the study. ANGPTL-4 and galectin-3 were significantly higher in CAD than the NC group. ANGPTL-4 showed significant negative correlation with GRACE score in acute coronary syndrome (ACS) ( r = -0.211, p = 0.03) patients. ANGPTL-4 showed significant positive correlation with serum creatinine ( r = 0.304, p = 0.056) and body mass index (BMI) ( r = 0.424, p = 0.009) in CSA patients. A modest positive correlation was observed between the serum galectin-3 levels and GRACE score ( r = 0.187, p = 0.055) in ACS patients. However, on multivariate analysis the positive correlation relationship between ANGPTL-4 and galectin-3 with the severity of CAD was not sustained. CONCLUSION: In conclusion, ANGPTL-4 and galectin-3 do not appear to have a promising role for assessing the severity of CAD. Nevertheless these biomarkers do warrant further exploration in improving the management of CAD.

Avaliação da Senescência de Células Sanguíneas Mononucleares Periféricas e na Disfunção Endotelial entre Adultos com Alto Risco Cardiovascular / Assessment of Peripheral Blood Mononuclear Cells Senescence and Endothelial Dysfunction among Adults with High Cardiovascular Risk

Resumo Fundamento Doenças cardiovasculares (DCV) são uma das principais causas de mortalidade e morbidade em todo o mundo. O envelhecimento biológico tem sido associado à ocorrência de resultados cardiovasculares. Entretanto, o mecanismo subjacente desse processo ainda é desconhecido. Objetivos Buscamos avaliar se a senescência das células sanguíneas mononucleares periféricas (CSMP) e biomarcadores endoteliais poderiam influenciar o risco cardiovascular (CV) e ser marcadores adequados para a detecção precoce de doenças cardiovasculares em adultos. Métodos Neste estudo transversal, pacientes livres de DCV foram classificados como baixo (n=32) e alto (n=28) escore de risco intracardaco (IHR) A senescência das CSMP foi avaliada estimando-se a atividade de telomerase (AT) e detectando-se a presença de células senescentes e disfunção endotelial, estimando-se a concentração de nitrito e nitrato e a capacidade antioxidante total (CAT). A análise estatística foi realizada com o software SPSS, versão 16.0 (SPSS Inc., Chicago, IL). Todos os p-valores <0,05 foram considerados estatisticamente significativos. Resultados A senescência de CSMP de 0,95 [p-valor = 0,0001; 95% IC (0,874-1,026)] foi um indicador significativo de pacientes com escore de IHR mais alto, com um valor de corte de 21,65, com sensibilidade e especificidade de 92% e 88% respectivamente. Identificou-se que a senescência de CSMP, nitrito e nitrato, e AT eram independentemente associadas a um escore de IHR alto. Conclusão Os status de nitrito e nitrato e AT, e a senescência de CSMP são medidas adequadas para prever o alto risco cardiovascular em adultos com risco CV. Entretanto devem ser realizados estudos de acompanhamento de longo prazo para confirmar esses achados. (Arq Bras Cardiol. 2021; 116(1):37-47)

Abstract Background Cardiovascular diseases (CVD) are one of the leading causes of mortality and morbidity worldwide. Biological aging has been associated with the occurrence of adverse cardiovascular outcomes; however, the underlying mechanism of this process remains unknown. Objectives This study sought to evaluate if peripheral blood mononuclear cell (PBMC) senescence and endothelial biomarkers could influence cardiovascular (CV) risk and be suitable markers for the early detection of cardiovascular diseases in adults. Methods In this cross-sectional study patients free of CVD were classified as lower (n=32) and higher Interheart Risk (IHR) scores (n=28). PBMC senescence was assessed by estimating the telomerase activity (TA) and detecting the presence of senescent cells and endothelial dysfunction by estimating the concentration of nitrite and nitrate and of total antioxidant capacity (TAC). Statistical analysis was performed with SPSS version 16.0 (SPSS Inc., Chicago, IL). All p-values <0.05 were considered statistically significant. Results PBMC senescence 0.95 [p-value = 0.0001; 95% CI (0.874-1.026)] was a significant predictor of patients with higher IHR scores with a cut-off value of 21.65 with a sensitivity and specificity of 92% and 88% respectively. PBMC senescence, nitrite and nitrate and TA were found to be independently associated with high IHR scores. Conclusion PBMC senescence, TA and nitrite, and nitrate status are suitable measures to predict high cardiovascular risk in adults with CV risk. Nevertheless, long-term follow-up studies are needed to confirm these findings. (Arq Bras Cardiol. 2021; 116(1):37-47)