Study of maternal and perinatal outcome in case of premature rupture of membrane at term

Background: Premature rupture of membranes is characterized by the rupture of membranes before the onset of true labour. PROM is associated with a high risk of maternal morbidity and also perinatal morbidity and mortality. The objective of this study was the evaluation of various risk factors and maternal and perinatal outcomes for a better understanding of this oracular condition for its better understanding and timely management.Methods: This study was carried out on 75 cases of PROM fulfilling set criteria over one year at a tertiary care hospital of western India. Demographic details, risk factors and outcomes were studied.Results: Present study found the highest number of cases among the age group 21-24 years. 70% of patients were primigravida and almost 75% were un-booked. Around 2/3rd of cases were delivered vaginally, having the highest no of maternal and perinatal morbidity and mortality when the duration of PROM increased to more than 24 hours.Conclusions: In our study, it was seen that PROM is more commonly seen in younger primigravida having certain risk factors. Many delivered vaginally. Complications increased with increasing duration of PROM. Early recognition of premature rupture of membranes and their associated complications and appropriate management of the situation helps in reducing the problems due to PROM to a great extent

A prospective study on causality, severity and preventability assessment of adverse drug reactions in a tertiary care hospital in India

Background: The present study was undertaken to evaluate the incidence and pattern of adverse drug reaction (ADRs), causality, severity and preventability of ADRs.Methods: Data was collected and analyzed with the information such as patients’ demographic details, associated co-morbid conditions and detailed drug related information gathered from ADR reporting forms. World Health Organization (WHO) scale was used for assessing causality, modified Hartwig scale was used for assessing severity and modified Schumock and Thorntons scale were used for assessing preventability of ADRs. Data was analyzed using descriptive statistics.Results: Total 154 ADRs were reported in a period of one year (August 2016- July 2017). Out of 154 ADRs analyzed, 120 (77.9%) were in adults, 33 (21.4%) pediatric and 01 (0.7%) in geriatric patients. The most common ADR recorded was cutaneous reactions (43.5%) and the most common causative class of drugs for the same was found to be antimicrobials (46.7%) followed by non-steroidal anti-inflammatory drugs (15.6%). Causality assessment scale indicated 68.8% ADRs possible and 24% ADRs as probable. Severity assessment revealed that 45.5 % were mild, 50.6% moderate and 3.9% ADRs severe. Preventability assessment showed 84.4% of the cases were probably non-preventable.Conclusions: In this study it was found that, most of the ADRs were of possible category with mild to moderate severity and majority being non-preventable. Antimicrobial drugs being the most common offending drug class causing ADRs. Strategies targeting appropriate and cautious use of this class of drugs may benefit in reducing the number of ADRs and therefore the cost involved in the treatment

Pyrroline-5-Carboxylate Reductase-2 Promotes Colorectal Carcinogenesis by Modulating Microtubule-Associated Serine/Threonine Kinase-like/Wnt/β-Catenin Signaling

Background: Despite significant progress in clinical management, colorectal cancer (CRC) remains the third most common cause of cancer-related deaths. A positive association between PYCR2 (pyrroline-5-carboxylate reductase-2), a terminal enzyme of proline metabolism, and CRC aggressiveness was recently reported. However, how PYCR2 promotes colon carcinogenesis remains ill understood. Methods: A comprehensive analysis was performed using publicly available cancer databases and CRC patient cohorts. Proteomics and biochemical evaluations were performed along with genetic manipulations and in vivo tumor growth assays to gain a mechanistic understanding. Results: PYCR2 expression was significantly upregulated in CRC and associated with poor patient survival, specifically among PYCR isoforms (PYCR1, 2, and 3). The genetic inhibition of PYCR2 inhibited the tumorigenic abilities of CRC cells and in vivo tumor growth. Coinciding with these observations was a significant decrease in cellular proline content. PYCR2 overexpression promoted the tumorigenic abilities of CRC cells. Proteomics (LC-MS/MS) analysis further demonstrated that PYCR2 loss of expression in CRC cells inhibits survival and cell cycle pathways. A subsequent biochemical analysis supported the causal role of PYCR2 in regulating CRC cell survival and the cell cycle, potentially by regulating the expression of MASTL, a cell-cycle-regulating protein upregulated in CRC. Further studies revealed that PYCR2 regulates Wnt/β-catenin-signaling in manners dependent on the expression of MASTL and the cancer stem cell niche. Conclusions: PYCR2 promotes MASTL/Wnt/β-catenin signaling that, in turn, promotes cancer stem cell populations and, thus, colon carcinogenesis. Taken together, our data highlight the significance of PYCR2 as a novel therapeutic target for effectively treating aggressive colon cancer

Genomic context and TP53 allele frequency define clinical outcomes in TP53-mutated myelodysplastic syndromes

TP53 mutations are associated with adverse outcomes and shorter response to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS). Limited data have evaluated the impact of the type, number, and patterns of TP53 mutations in response outcomes and prognosis of MDS. We evaluated the clinicopathologic characteristics, outcomes, and response to therapy of 261 patients with MDS and TP53 mutations. Median age was 68 years (range, 18-80 years). A total of 217 patients (83%) had a complex karyotype. TP53 mutations were detected at a median variant allele frequency (VAF) of 0.39 (range, 0.01-0.94). TP53 deletion was associated with lower overall response rate (ORR) (odds ratio, 0.3; P = .021), and lower TP53 VAF correlated with higher ORR to HMAs. Increase in TP53 VAF at the time of transformation was observed in 13 patients (61%), and previously undetectable mutations were observed in 15 patients (65%). TP53 VAF was associated with worse prognosis (hazard ratio, 1.02 per 1% VAF increase; 95% confidence interval, 1.01-1.03; P \u3c .001). Integration of TP53 VAF and karyotypic complexity identified prognostic subgroups within TP53-mutant MDS. We developed a multivariable model for overall survival that included the revised International Prognostic Scoring System (IPSS-R) categories and TP53 VAF. Total score for each patient was calculated as follows: VAF TP53 + 13 × IPSS-R blast score + 16 × IPSS-R cytogenetic score + 28 × IPSS-R hemoglobin score + 46 × IPSS-R platelet score. Use of this model identified 4 prognostic subgroups with median survival times of not reached, 42.2, 21.9, and 9.2 months. These data suggest that outcomes of patients with TP53-mutated MDS are heterogeneous and that transformation may be driven not only by TP53 but also by other factors

Gastrointestinal stromal tumour in Meckel's diverticulum

<p>Abstract</p> <p>Background</p> <p>Meckel's Diverticulum is the most commonly encountered congenital anomaly of the small intestine, occurring in approximately 2% of the population. Occasionally Meckel's diverticulum harbors neoplasms.</p> <p>Case presentation</p> <p>A 65 year old gentleman, presented with a pelvic mass. On exploratory laparotomy, it turned out to be gastrointestinal stromal tumour (GIST) arising from Meckel's diverticulum. Short history and review of literature are discussed.</p> <p>Conclusion</p> <p>Neoplasms occurring from Meckel's diverticulum, even though rare, should be considered as differential diagnosis of pelvic masses arising from bowel, wherever imaging modalities fail to give a definitive diagnosis.</p

Activating the knowledge-to-action cycle for geriatric care in India

Despite a rapidly aging population, geriatrics - the branch of medicine that focuses on healthcare of the elderly - is relatively new in India, with many practicing physicians having little knowledge of the clinical and functional implications of aging. Negative attitudes and limited awareness, knowledge or acceptance of geriatrics as a legitimate discipline contribute to inaccessible and poor quality care for India's old. The aim of this paper is to argue that knowledge translation is a potentially effective tool for engaging Indian healthcare providers in the delivery of high quality geriatric care. The paper describes India's context, including demographics, challenges and current policies, summarizes evidence on provider behaviour change, and integrates the two in order to propose an action plan for promoting improvements in geriatric care

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Somatic mutational landscape of hereditary hematopoietic malignancies caused by germline variants in <i>RUNX1</i>, <i>GATA2</i>, and <i>DDX41</i>

Individuals with germ line variants associated with hereditary hematopoietic malignancies (HHMs) have a highly variable risk for leukemogenesis. Gaps in our understanding of premalignant states in HHMs have hampered efforts to design effective clinical surveillance programs, provide personalized preemptive treatments, and inform appropriate counseling for patients. We used the largest known comparative international cohort of germline RUNX1, GATA2, or DDX41 variant carriers without and with hematopoietic malignancies (HMs) to identify patterns of genetic drivers that are unique to each HHM syndrome before and after leukemogenesis. These patterns included striking heterogeneity in rates of early-onset clonal hematopoiesis (CH), with a high prevalence of CH in RUNX1 and GATA2 variant carriers who did not have malignancies (carriers-without HM). We observed a paucity of CH in DDX41 carriers-without HM. In RUNX1 carriers-without HM with CH, we detected variants in TET2, PHF6, and, most frequently, BCOR. These genes were recurrently mutated in RUNX1-driven malignancies, suggesting CH is a direct precursor to malignancy in RUNX1-driven HHMs. Leukemogenesis in RUNX1 and DDX41 carriers was often driven by second hits in RUNX1 and DDX41, respectively. This study may inform the development of HHM-specific clinical trials and gene-specific approaches to clinical monitoring. For example, trials investigating the potential benefits of monitoring DDX41 carriers-without HM for low-frequency second hits in DDX41 may now be beneficial. Similarly, trials monitoring carriers-without HM with RUNX1 germ line variants for the acquisition of somatic variants in BCOR, PHF6, and TET2 and second hits in RUNX1 are warranted