Study of the Risk Factors for Cesarean Delivery in Induced Labors at Term.

BACKGROUND: Induction of labor has become one of the most common interventions in obstetrics. Induction is indicated when the benefits to either mother or fetus outweigh those of continuing the pregnancy. Maternal complication rates that are increased in association with labor induction include cesarean delivery, chorioamnionitis, abruptio placentae, and uterine atony. So identifying those pregnancies that can be induced with low risk of cesarean delivery is important. The aim of this study was to identify those factors which influence the risk of emergency cesarean delivery in induced labors at term. METHODS: It is a case-control study conducted at Tertiary care center and affiliated hospitals. In this study, odds ratio with 95 % confidence interval is taken as a measure of relative risk. Patients were evaluated for risk factors for cesarean section using logistic regression. Cases include all women who were induced at term and delivered by emergency cesarean section. Controls include all women who were induced at term and delivered vaginally. RESULTS: The risk factors for cesarean delivery are advanced maternal age at delivery (≥35 years), high early pregnancy body mass index (≥30 kg/m(2)), nulliparity, low preinduction Bishops score (<5), gestational diabetes mellitus, and intrauterine growth restriction. CONCLUSION: Women with multiple risk factors for cesarean can be taken up for elective cesarean section rather than inducing them at term.

Ramucirumab for the treatment of gastroesophageal cancers.

INTRODUCTION: In 2014, the U.S. Food and Drug Administration (FDA) approved ramucirumab for use in the second line setting of advanced or metastatic, gastric or gastroesophageal adenocarcinoma (GEAC) based on the result of Phase III clinical trials; REGARD and RAINBOW. AREAS COVERED: We briefly review the mechanisms of angiogenesis, anti-angiogenic therapy, and current status of advanced GEAC treatment then highlight the challenges and future prospects of novel molecular targeted agents. EXPERT OPINION: Although both the REGARD and RAINBOW trials met their primary endpoints of significantly prolonged overall survival (OS) and progression-free survival (PFS), the magnitude of the difference is still relatively modest. Given that ramucirumab alone has a marginal effect, a combination of paclitaxel and ramucirumab is strongly preferred as a second line therapy. To maximize the impact of ramucirumab in patients with GEAC, we can leverage the recent pharmacokinetics (PK) data of ramucirumab from the REGARD and RAINBOW trials. In addition, the quest for identifying biomarkers to select patients who are likely to benefit the most should continue. It is our firm belief that taxanes should no longer be added to the frontline regimens in most cases, given the success of the taxane/ramucirumab in the second line setting.

Problem-based learning research in anesthesia teaching: current status and future perspective.

The teaching curriculum in anesthesia involves traditional teaching methods like topic-based didactic lectures, seminars, and journal clubs; intraoperative apprenticeship; and problem-based learning (PBL) and simulation. The advantages of incorporating PBL in anesthesia teaching include development of skills like clinical reasoning, critical thinking, and self-directed learning; in addition it also helps in developing a broader perspective of case scenarios. The present paper discusses the characteristics, key elements, and goals of PBL; various PBL methods available; lacunae in the existing knowledge of PBL research; its current status and future perspectives in anesthesia teaching.

Complete congenital foetal heart block: a case report.

Congenital heart block (CHB) is the most severe manifestation of neonatal lupus which can develop into a lethal atrioventricular (AV) block. Complete congenital foetal heart block related to maternal anti-Ro/SSA autoanti-bodies typically develops between 20 and 24 weeks of gestation. CHB with a structurally normal heart is frequently associated with maternal autoantibodies to Ro/SSA and La/SSB. We are presenting a case of foetal complete CHB with high maternal Ro/SSA and La/SSB titre with favourable outcome.

ALDH-1 expression levels predict response or resistance to preoperative chemoradiation in resectable esophageal cancer patients.

PURPOSE: Operable thoracic esophageal/gastroesophageal junction carcinoma (EC) is often treated with chemoradiation and surgery but tumor responses are unpredictable and heterogeneous. We hypothesized that aldehyde dehydrogenase-1 (ALDH-1) could be associated with response. METHODS: The labeling indices (LIs) of ALDH-1 by immunohistochemistry in untreated tumor specimens were established in EC patients who had chemoradiation and surgery. Univariate logistic regression and 3-fold cross validation were carried out for the training (67% of patients) and validation (33%) sets. Non-clinical experiments in EC cells were performed to generate complimentary data. RESULTS: Of 167 EC patients analyzed, 40 (24%) had a pathologic complete response (pathCR) and 27 (16%) had an extremely resistant (exCRTR) cancer. The median ALDH-1 LI was 0.2 (range, 0.01-0.85). There was a significant association between pathCR and low ALDH-1 LI (p ≤ 0.001; odds-ratio [OR] = 0.432). The 3-fold cross validation led to a concordance index (C-index) of 0.798 for the fitted model. There was a significant association between exCRTR and high ALDH-1 LI (p ≤ 0.001; OR = 3.782). The 3-fold cross validation led to the C-index of 0.960 for the fitted model. In several cell lines, higher ALDH-1 LIs correlated with resistant/aggressive phenotype. Cells with induced chemotherapy resistance upregulated ALDH-1 and resistance conferring genes (SOX9 and YAP1). Sorted ALDH-1+ cells were more resistant and had an aggressive phenotype in tumor spheres than ALDH-1- cells. CONCLUSIONS: Our clinical and non-clinical data demonstrate that ALDH-1 LIs are predictive of response to therapy and further research could lead to individualized therapeutic strategies and novel therapeutic targets for EC patients.

Results of the baseline positron emission tomography can customize therapy of localized esophageal adenocarcinoma patients who achieve a clinical complete response after chemoradiation.

BACKGROUND: Patients with localized esophageal adenocarcinoma (EAC) who achieve a clinical complete response (clinCR) after preoperative chemoradiation (trimodality therapy; TMT) or definitive chemoradiation (bimodality therapy; BMT) live longer than those who achieve a

Mortalin-p53 interaction in cancer cells is stress dependent and constitutes a selective target for cancer therapy.

Stress protein mortalin is a multifunctional protein and is highly expressed in cancers. It has been shown to interact with tumor suppressor protein-p53 (both wild and mutant types) and inactivates its transcriptional activation and apoptotic functions in cancer cells. In the present study, we found that, unlike most of the cancer cells, HepG2 hepatoma lacked mortalin-p53 interaction. We demonstrate that the mortalin-p53 interaction exists in cancer cells that are either physiologically stressed (frequently associated with p53 mutations) or treated with stress-inducing chemicals. Targeting mortalin-p53 interaction with either mortalin small hairpin RNA or a chemical or peptide inhibitor could induce p53-mediated tumor cell-specific apoptosis in hepatocellular carcinoma; p53-null hepatoma or normal hepatocytes remain unaffected.

Molecular characterization of apoptosis induced by CARF silencing in human cancer cells.

Collaborator of ARF (CARF) was cloned as an ARF-interacting protein and shown to regulate the p53-p21(WAF1)-HDM2 pathway, which is central to tumor suppression via senescence and apoptosis. We had previously reported that CARF inhibition in cancer cells led to polyploidy and caspase-dependent apoptosis, however, the mechanisms governing this phenomenon remained unknown. Thus, we examined various cell death and survival pathways including the mitochondrial stress, ataxia telangiectasia mutated (ATM)-ATR, Ras-MAP kinase and retinoblastoma cascades. We found that CARF is a pleiotropic regulator with widespread effects; its suppression affected all investigated pathways. Most remarkably, it protected the cells against genotoxicity; CARF knockdown elicited DNA damage response as evidenced by increased levels of phosphorylated ATM and γH2AX, leading to induction of mitotic arrest and eventual apoptosis. We also show that the CARF-silencing-induced apoptosis in vitro translates to in vivo. In a human tumor xenograft mouse model, treatment of developing tumors with short hairpin RNA (shRNA) against CARF via an adenovirus carrier induced complete suppression of tumor growth, suggesting that CARF shRNA is a strong candidate for an anticancer reagent. We demonstrate that CARF has a vital role in genome preservation and tumor suppression and CARF siRNA is an effective novel cancer therapeutic agent.

Evaluation of the anti-genotoxicity of leaf extract of Ashwagandha.

We have undertaken the studies to investigate the presence of various activities of the leaf extract of Ashwagandha (Lash), a commonly used shrub in Indian traditional medicine, Ayurveda. In the present study, we studied the effect of Lash against MNNG-induced genotoxicity in onion root tip cells. We report that Lash offered substantial protection against the mutagenic effects of MNNG.

Evaluation of the anti-proliferative and anti-oxidative activities of leaf extract from in vivo and in vitro raised Ashwagandha.

Withania somnifera (Ashwagandha) is used in Indian traditional medicine, Ayurveda and is believed to have a variety of health promoting effects. Molecular mechanisms and pathways underlying these effects have not been studied. We tried to characterize various activities of leaf extract of Ashwagandha (Lash) raised in the field and in the laboratory. We found that the Lash from field-raised plants has a significant anti-proliferative activity in human tumorigenic cells. However, it did not impart any protection against the oxidative damage caused by high glucose and hydrogen peroxide to human tumor cells suggesting that it can be used as an anti-tumor, but not as an anti-oxidant, substance.

The ARF-p53 senescence pathway in mouse and human cells.

Mouse and human cells have most frequently been used for studies that have led to the elucidation of various molecular pathways involved in senescence. The ARF-p53 pathway has been assigned as one of the major protagonists in these phenomena. ARF is an alternative reading frame protein encoded along with p16INK4A by the INK4a locus on human chromosome 9p21 and the corresponding locus on mouse chromosome 4. Whereas the mouse ARF (p19ARF) consists of 169 amino acids, the human ARF (p14ARF) consists of 132 amino acids, truncated at the C-terminus. Molecular studies on the regulation of ARF activity by its binding partners have revealed that mouse ARF protein, but not human ARF protein, interacts with a cytoplasmic protein, Pex19p. This interaction of mouse ARF with Pex19p results in its milder p53 activation function in mouse cells as compared to human cells and thus accounts, at least in part, for the weaker tumor surveillance and frequent immortalization of mouse cells.

Laparoscopic Management of Adnexal Masses.

Retrospective study of 121 cases of adnexal masses which were managed laparoscopically was carried out. The aim of study was to evaluate the safety and effectiveness of laparoscopic management of adnexal masses. In 120 cases, procedure was completed safely with minimum morbidity. In one case laparotomy had to be done to complete the procedure. In 76 cases cystectomy was done, 26 required salpingo-oophorectomy and 19 required only salpingectomy. Histologic evaluation revealed 30 functional cysts, 36 endometriotic cysts, 11 dermoids, 9 serous cystadenomas, 3 mucinous cystadenomas, 11 parovarian cysts, 19 cases of hydrosalpinx and 2 cases of tuberculosis.

Laparoscopic Management of Ectopic Pregnancies.

To compare the laparoscopic approach with laparotomy in the treatment of ectopic pregnancy, a retrospective analysis involving 52 patients with ectopic pregnancies was done. The aim of this study was to evaluate the safety and efficacy of laparoscopic surgery for ectopic pregnancies. 30 patients underwent laparoscopic management while 22 patients were managed by conventional laparotomy. In the laparoscopic group, the postoperative morbidity and post-hospital stay were significantly less. Although laparoscopic surgery for ectopic pregnancies is a new approach and it is not widely practised in service hospitals, it has more advantages than open surgery and it has been well accepted by the surgeons and patients. It is a safe and feasible approach.

Fertility Enhancing Hysteroscopic Surgery: Our Experience.

690 hysteroscopies done over a period of four and a half years for infertility were evaluated. 85 therapeutic hysteroscopic procedures like hysterscopic metroplasty, lysis of intrauterine adhesions, electroresection of fibroids, removal of foreign bodies and cornual cannulation were carried out. These minimally invasive procedures were associated with satisfying results, least morbidity, shorter hospital stay and high patient satisfaction.

Transcervical Resection of Endometrium - Will it edge out Hysterectomy.

The most frequent indication for hysterectomy is menorrhagia, even though the uterus is normal in a large number of patients. Transcervical resection of the endometrium (TCRE) is a less drastic alternative, but success rates have varied and menorrhagia can recur. 60 patients with menorrhagia due to various causes who failed to respond to medical therapy and did not desire pregnancy and hysterectomy underwent TCRE with hysteroscope. 56 cases have been followed up postoperatively for 3 years. The primary endpoints were women's satisfaction and need for further surgery. The proportion of patients who attained amennorhea 24 months after the procedure was 44.4% and the percentage of patients who attained hypomennorhea was 44.4%. The patients satisfaction rate after 24 months of follow up was 88.8%. Failure of TCRE procedure was encountered in 6.6% of patients. Randomized comparison with hysterectomy has shown short-term benefits in the form of shorter operating time, fewer complications and faster rates of recovery and almost as high satisfaction levels. TCRE is an effective procedure in treating menorrhagia and is an acceptable alternative to medical management and hysterectomy in the treatment of menorrhagia for many women with no other serious disorders.

Mortalin: a potential candidate for biotechnology and biomedicine.

Mortalin is a novel member of the hsp70 family of proteins that exhibits a different staining pattern in normal and immortal cells. It was also cloned as glucose regulated protein, GRP75 and peptidebinding protein, PBP74. It has been assigned multiple functions ranging from stress response, intracellular trafficking, antigen processing, control of cell proliferation, differentiation and tumorigenesis. The present article compiles and reviews information on multiple sites and functions of mortalin. In view of its upregulation in many tumors and transcriptional inactivation function of p53, its potential use in biotechnology and biomedicine is discussed.

Office Hysteroscopy: An Insight.

In clinical gynaecology, one comes across a large number of patients with intra-uterine pathology. Various investigations have been devised to evaluate these disorders. Hysteroscopy, since its advent has progressed a long way to be recognized as the gold standard in diagnosing intra-uterine pathologies. An attempt to make it an OPD procedure was encouraging. 100 cases of office hysteroscopy were performed at our centre. Pain, patient comfort and acceptability were studied. A favourable outcome was achieved and wider application is recommended.