Endometriosis and adverse maternal, fetal and neonatal outcomes, a systematic review and meta-analysis.

STUDY QUESTION: How is endometriosis associated with adverse maternal, fetal and neonatal outcomes of pregnancy? SUMMARY ANSWER: Women with endometriosis are at elevated risk for serious and important adverse maternal (pre-eclampsia, gestational diabetes, placenta praevia and Cesarean section) and fetal or neonatal outcomes (preterm birth, PPROM, small for gestational age, stillbirth and neonatal death). WHAT IS KNOWN ALREADY: A number of studies have shown an association between endometriosis and certain adverse maternal and fetal outcomes, but the results have been conflicting with potential for confounding by the use of assisted reproductive technology. STUDY DESIGN, SIZE, DURATION: A systematic review and meta-analysis of observational studies (1 January 1990-31 December 2017) that evaluated the effect of endometriosis on maternal, fetal and neonatal outcomes was conducted. PARTICIPANTS/MATERIALS, SETTING, METHODS: Studies were considered for inclusion if they were prospective or retrospective cohort or case-control studies; included women greater than 20 weeks gestational age with endometriosis; included a control group of gravid women without endometriosis; and, reported at least one of the outcomes of interest. Each study was reviewed for inclusion, data were extracted and risk of bias was assessed by two independent reviewers. MAIN RESULTS AND THE ROLE OF CHANCE: The search strategy identified 33 studies (sample size, n = 3 280 488) for inclusion. Compared with women without endometriosis, women with endometriosis had higher odds of pre-eclampsia (odds ratio [OR] = 1.18 [1.01-1.39]), gestational hypertension and/or pre-eclampsia (OR = 1.21 [1.05-1.39]), gestational diabetes (OR = 1.26 [1.03-1.55]), gestational cholestasis (OR = 4.87 [1.85-12.83]), placenta praevia (OR = 3.31 [2.37, 4.63]), antepartum hemorrhage (OR = 1.69 [1.38-2.07]), antepartum hospital admissions (OR = 3.18 [2.60-3.87]), malpresentation (OR = 1.71 [1.34, 2.18]), labor dystocia (OR = 1.45 [1.04-2.01]) and cesarean section (OR = 1.86 [1.51-2.29]). Fetuses and neonates of women with endometriosis were also more likely to have preterm premature rupture of membranes (OR = 2.33 [1.39-3.90]), preterm birth (OR = 1.70 [1.40-2.06]), small for gestational age <10th% (OR = 1.28 [1.11-1.49]), NICU admission (OR = 1.39 [1.08-1.78]), stillbirth (OR = 1.29 [1.10, 1.52]) and neonatal death (MOR = 1.78 [1.46-2.16]). Among the subgroup of women who conceived spontaneously, endometriosis was found to be associated with placenta praevia, cesarean section, preterm birth and low birth weight. Among the subgroup of women who conceived with the use of assisted reproductive technology, endometriosis was found to be associated with placenta praevia and preterm birth. LIMITATIONS, REASONS FOR CAUTION: As with any systematic review, the review is limited by the quality of the included studies. The diagnosis for endometriosis and the selection of comparison groups were not uniform across studies. However, the effect of potential misclassification would be bias towards the null hypothesis. WIDER IMPLICATIONS OF THE FINDINGS: The association between endometriosis with the important and serious pregnancy outcomes observed in our meta-analysis, in particular stillbirth and neonatal death, is concerning and warrants further studies to elucidate the mechanisms for the observed findings. STUDY FUNDING/COMPETING INTEREST(S): Dr Shifana Lalani is supported by a Physicians' Services Incorporated Foundation Research Grant, and Dr Innie Chen is supported by a University of Ottawa Clinical Research Chair in Reproductive Population Health and Health Services. Dr Singh declares conflicts of interests with Bayer, Abvie, Allergan and Cooper Surgical. All other authors have no conflicts of interests to declare. REGISTRATION NUMBER: PROSPERO CRD42015013911.

Inotuzumab ozogamicin for the treatment of patients with acute lymphocytic leukemia.

Inotuzumab ozogamicin is an antibody-drug conjugate comprised of a humanized anti-CD22 monoclonal antibody conjugated to calicheamicin, a cytotoxic antibiotic agent. Inotuzumab ozogamicin binds to CD22-expressing tumor cells, resulting in apoptotic cell death. Based on the results of the pivotal, phase III INO-VATE trial in acute lymphoblastic leukemia (ALL), approval of inotuzumab ozogamicin was recently granted for the treatment of patients with relapsed or refractory ALL, a group that otherwise has a poor prognosis with standard chemotherapy. Several ongoing clinical trials are now testing whether outcomes can be further improved by combining inotuzumab ozogamicin with low-dose chemotherapy or by including inotuzumab ozogamicin in the front-line setting. In this article we discuss the preclinical, clinical and safety data of inotuzumab ozogamicin.

Characteristics, risk factors, and treatment practices of known adult hypertensive patients in saudi arabia.

Objective. To determine the prevalence, risk factors, characteristics, and treatment practices of known adult hypertensives in Saudi Arabia. Methods. Cross-sectional community-based study using the WHO stepwise approach. Saudi adults were randomly chosen from Primary Health Care Centers catchment areas. Data was collected using a questionnaire which included sociodemographic data, history of hypertension, risk factors, treatment practices, biochemical and anthropometric measurements. Collected data was cheeked, computer fed, and analysed using SPSS V17. Results. Out of 4719 subjects (99.2% response), 542 (11.5%) subjects were known hypertensives or detected by health workers in the past 12 months. Hypertension was significantly associated with age, gender, geographical location, education, employment, diabetes, physical inactivity, excess body weight, and ever smoking. Multiple logistic analysis controlling for age showed that significant predictors of hypertension were diabetes mellitus, ever smoking, obesity, and hypercholesteremia. Several treatment modalities and practices were significantly associated with gender, age, education, and occupation. About 74% were under prescribed treatment by physicians, 62% on dietary modification, 37% attempted weight reduction, 27% performed physical exercise, and less than 7% used herbs, consulted traditional healers or quitted smoking. Income was not significantly associated with any treatment modality or patient practices. Conclusion. Hypertension (known and undetected) is a major chronic health problem among adults in Saudi Arabia. Many patients' practices need changes. A comprehensive approach is needed to prevent, early detect, and control the disease targeting, the risk factors, and predictors identified.

Neoadjuvant and adjuvant therapy with imatinib for locally advanced gastrointestinal stromal tumors in eastern Indian patients.

BACKGROUND: Imatinib mesylate is able to at least modify the course of gastrointestinal stromal tumours (GISTs). Neoadjuvant use for locally advanced lesions is evolving as a new treatment paradigm in this hitherto universally fatal disease. METHODS AND RESULTS: The study patients with locally advanced GIST received neoadjuvant and adjuvant imatinib mesylate. Response was noted as per the RECIST protocol and overall progression free survival was reported. Of 19 patients (mean age 38.5 years, range 26 yrs to 64 yrs) studied, 13 achieved partial response (PR) and 6 a stationary disease (SD) on preoperative imatinib. Histopathological evaluation and grading of responses revealed only moderate and low grade pathological response after imatinib. R0 resection was possible in 13/19 and R1 in 6/19. Imatinib was well tolerated and adverse reactions were minimal. Post operative complications of surgery were not out of the ordinary for a surgical series featuring extensive abdominal surgery. CONCLUSION: Preoperative imatinib in locally advanced GIST seems to be a reasonable option for locally advanced GIST patients and enough downstaging to allow a resection with microscopically negative margins can be expected in a fairly good proportion of patients.

Hajj-associated acute respiratory infection among hajjis from Riyadh.

A prospective cohort study was conducted to estimate the incidence of acute respiratory infections (ARI) among hajjis registered at primary health care centres of Riyadh. Out of 1027 hajjis, 39.8% developed symptoms of ARI. The incidence of ARI was not statistically significantly associated with age, sex, educational status or smoking. The risk of illness was significantly higher among diabetics, hajjis who stayed longer in the hajj area and who prayed at Namera mosque. Use of a facemask by men, but not use of a facecover by women, was a significant protective factor against ARI.

Delay in the diagnosis and prognosis of caecal carcinoma--a study of 20 cases.

BACKGROUND: Caecum is the dilated part of the right colon situated in the right iliac fossa, therefore the etiology of this cancer is similar to those of the rest of the colon. Caecal carcinoma is more common in developed countries but it is not a rare disease in underdeveloped countries. This is more common in high socio-economic people who use less fibrous and purified diet. With improvement in health education and social status of the people of Pakistan, there is an emerging trend of Westernization in our society. This may increase the incidence of cancer in Pakistan. Carcinoma of caecum is curable disease is diagnosed early and treated. If we are aware of the pathogenesis, etiology, clinical presentation and management of the disease, we can offer a lot to these patients by diagnosing the caecal carcinoma at an earlier stage, this was the aim of this study. METHODS: 20 cases (15 males and 5 females) of Carcinoma of Caecum were studied from January 1997 to December 1999. Out of these six patients presented in emergency ward, 2 as acute appendicitis and 4 as intestinal obstruction. After routine non-specific investigations, our specific investigations included USG abdomen, barium contrast studies and colonoscopy, Barium study and USG remained of primary importance. RESULTS: Most of the patients were between age 45-65 years, oldest patient being 80 years old and the youngest was of only 30 years. Most of the patients presented as mass in the right iliac fossa and only some patients as intestinal obstruction. Right hemicolectomy with primary ileo-transverse anastomosis was our standard surgical procedure and was done in about 14 cases. But in some cases ileo-transverse by-pass operation was done as the growth was locally advanced. However, only the omental biopsy was taken in the cases where carcinoma was too advanced. CONCLUSIONS: We think that our sociodemographic factors put a hindrance in detection of this carcinoma at early stages and therefore curative procedures are difficult to bear good results.

Typing of eight short tandem repeat (STR) loci in a Saudi Arabian population.

Allele frequency data for eight short tandem repeat (STR) loci, HUMF13A01, HUMFESFPS, HUMF13B, HUMLPL, HUMCSF1PO, HUMTPOX, HUMTHO1 and HUMvWA, were obtained for unrelated individuals in a Saudi Arabian population. All loci, except F13B (P = 0.037) and LPL (P = 0.035), meet Hardy-Weinberg expectations, based on the exact test. The most informative locus is HUMvWA (PD = 0.936) and the least discriminating is the HUMTPOX locus (PD = 0.820). There was only one observation of a departure from expectation from pairwise locus comparisons. These data can be used for estimating the frequency of STR profiles in a Saudi Arabian population.

Impaired interleukin-12 production in multiple sclerosis patients.

Multiple Sclerosis (MS), a disease of the human central nervous system, is believed to be a T cell mediated autoimmune disorder with genetic and environmental influences. Interleukin-12 (IL-12), a proinflammatory cytokine produced primarily by antigen presenting cells is a potent inducer of interferon-gamma (IFN-gamma) and other Th1 cytokines that may play an important role in MS pathogenesis. We have investigated IL-12 production induced by the T cell independent pathway in untreated and IFN-beta treated MS patients, healthy individuals and other neurological disease (OND) patients in response to the human pathogen Staphylococcus aureus. We report that peripheral blood mononuclear cells (PBMC) from untreated MS patients produce normal amounts of the biologically active IL-12 p70 heterodimer but significantly less free IL-12 p40 heavy chain than PBMC from both healthy and disease controls when challenged in vitro with Staphylococcus aureus. Both mRNA expression of the inducible IL-12 p40 chain and protein levels were found to be reduced in untreated MS patients. No decrease in the production of the IL-12 p40 was seen in MS patients on IFN-beta therapy. The decreased production of IL-12 p40 heavy chain is not attributed to increased IL-10 secretion, a defect in the production of cytokines by macrophages or the number of cytokine producing cells. The factor(s) responsible for the decrease in p40 remain to be determined. Since IL-12 p40 antagonizes the biological activity of IL-12 in vitro and in vivo, identification of a defect in the 'natural' antagonist of IL-12, may provide the basis for immune therapy.

Knowledge, attitude and behaviour towards AIDS among educated youth in Lahore, Pakistan.

OBJECTIVE: To assess the knowledge, attitude and behaviour regarding AIDS among educated young people in Lahore, Pakistan. METHODS: An anonymous survey of 733 males and 355 females was carried out using structured questionnaire among educated youth, selected randomly from non-medical educational institutions and work places. RESULTS: Knowledge on exsistance of AIDS in Pakistan was expressed by 698 (95.2%) males and 273 (76.9%) females, in, while only 189 (25.7%) males and 76 (21.4%) females knew its cause. Knowledge of the different modes of transmission was good, however 59%, 48%, 68% and 43% males; 28%, 45%, 59% and 35% females believed that it could be transmitted through sharing of utensils, mouth kissing, casual contact and mosquito bite, respectively. Ninety one percent males and 86% females believed that AIDS sufferers should be isolated. Extra marital sex was experienced by 6% subjects and only 5% used condoms. Generally, males had better knowledge than females except in attitudes towards monogamy and having sex with someone known. CONCLUSIONS: The study revealed gaps in the knowledge of females regarding AIDS and its transmission. The results indicates an urgent need to include health education syllabi emphasising AIDS and other Sexually Transmitted Diseases in the Curriculum of schools/colleges to convey the message adequately to the youth.

Developmental remodeling and shortening of the cardiac outflow tract involves myocyte programmed cell death.

The embryonic outflow tract is a simple tubular structure that connects the single primitive ventricle with the aortic sac and aortic arch arteries. This structure undergoes a complex sequence of morphogenetic processes to become the portion of the heart that aligns the right and left ventricles with the pulmonary artery and aorta. Abnormalities of the outflow tract are involved in many clinically significant congenital cardiac defects; however, the cellular and molecular processes governing the development of this important structure are incompletely understood. Histologic and tissue-tagging studies indicate that the outflow tract tissues compact and are incorporated predominantly into a region of the right ventricle. The hypothesis tested in the current study was that cell death or apoptosis in the muscular portion of the outflow tract is an important cellular mechanism for outflow tract shortening. The tubular outflow tract myocardium was specifically marked by infecting myocytes of the chicken embryo heart with a recombinant replication-defective adenovirus expressing beta-galactosidase (beta-gal) under the control of the cytomegalovirus promoter. Histochemical detection of the beta -gal-labeled outflow tract myocytes revealed that the tubular structure shortened to become a compact ring at the level of the pulmonic infundibulum over several days of development (stages 25-32, embryonic days 4-8). The appearance of apoptotic cardiomyocytes was correlated with OFT shortening by two histologic assays, TUNEL labeling of DNA fragments and AnnexinV binding. The rise and fall in the number of apoptotic myocytes detected by histologic analyses paralleled the change in activity levels of Caspase-3, a protease in the apoptotic cascade, measured in outflow tract homogenates. These results suggest that the elimination of myocytes by programmed cell death is one mechanism by which the outflow tract myocardium remodels to form the proper connection between the ventricular chambers and the appropriate arterial trunks.

Factors influencing the prescribing patterns in acute watery diarrhoea.

Two hundred sixty-two randomly sampled general physicians of Lahore were interviewed to study the current practices and factors affecting the management of acute watery diarrhoea (AWD) in children below 5 years of age. Among the physicians, 19% prescribed ORS alone, 61% ORS with some drug, 15% drugs alone and 5% increased fluid intake only. Physicians in government sector, recent graduates and those trained in a paediatrics unit prescribed more on the WHO guidelines (p<0.05). Attending a diarrhoea training unit (DTU) course, reading WHO guidelines for management of diarrhoea and total number of patients seen daily had no significant effect on prescribing practices. Two hundred fifty-five (97%) physicians thought that majority of other physicians prescribed drugs for the management of acute watery diarrhoea to satisfy the mothers of the children, their belief in the effectiveness of drugs and competition in practice.

An indirect fluorescent antibody (IFA) test for the serodiagnosis of Kala-Azar.

The IFA test developed using Leishmania donovani promastigote and amastigote antigens showed very high antibody titre in clinically and parasitologically established cases (30) of kala-azar, the geometrical mean reciprocal titre (GMRT) being 870 +/- 5.4 and 5370 +/- 1.80 respectively with the two antigens. In contrast, the GMRT of normal subjects of endemic area was only 12.44 +/- 6.19 and 80.35 +/- 1.66 respectively with these antigens. None of the subjects from non-endemic area suffering with other parasitic diseases, such as malaria, filaria, amoebiasis, leprosy or tuberculosis (20 cases each) gave a positive response to any of the antigen. The test holds promise in the diagnosis of Kala-azar.

Minitracheotomy Seldinger--assessment of a new technique.

A multicentre, prospective study of 26 patients was undertaken for the assessment of insertion of minitracheotomy tubes by the Seldinger technique. The technique of insertion is described. There were two misplacements, three blockages of the inserting Tuohy needle with fat, and six cases of difficulty in passing the minitracheotomy tube.

Enzyme-linked immunosorbent assay in the diagnosis of kala-azar in Bhadohi (Varanasi), India.

An enzyme-linked immunosorbent assay (ELISA) developed using Leishmania donovani promastigote soluble antigen gave positive responses in practically all the clinically and parasitologically diagnosed patients with kala-azar in a preliminary study. Healthy control subjects from non-endemic and endemic areas gave negative results. No cross-reaction was observed with patients having leprosy, filariasis, malaria, tuberculosis, or amoebiasis. Blood samples collected on filter paper were adequate for the test. The test appears promising in the diagnosis of kala-azar.

Minitracheotomy--a report of a proposed further development.

A simple modification of the method of insertion of a mini-tracheotomy using a Seldinger technique is described.

Anaesthesia for isolated lung transplantation.

The anaesthetic management of a patient undergoing successful, left-sided orthotopic single lung transplantation is presented. Problems, specific to the operation, are featured and discussed.