Aspirin for evidence-based preeclampsia prevention trial: effect of aspirin in prevention of preterm preeclampsia in subgroups of women according to their characteristics and medical and obstetrical history.

Objective: To examine whether there are differences in the effect of aspirin on the incidence of preterm-PE in the ASPRE trial in subgroups defined according to maternal characteristics and medical and obstetrical history. Study design: This was a secondary analysis of data from the ASPRE trial. In ASPRE women with singleton pregnancies had screening by means of an algorithm that combines maternal factors and biomarkers at 11-13 weeks’ gestation. Those with an estimated risk for preterm-PE of >1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg/day) vs. placebo from 11 to 14 until 36 weeks’ gestation. Aspirin was associated with a significant reduction in the incidence of preterm-PE with delivery at 90% of the prescribed medication. Results are presented as forest plot with P values for the interaction effects, group sizes, event counts and estimated odds ratios. We examined whether the test of interaction was significant at the 5% level with a Bonferroni adjustment for multiple comparisons. Results: There was no evidence of heterogeneity in the aspirin effect in subgroups defined according to maternal characteristics and obstetrical history. In participants with chronic hypertension preterm-PE occurred in 10.2% (5/49) in the aspirin group and in 8.2% (5/61) in the placebo group (adjusted odds ratio 1.29, 95% confidence interval, 0.33 to 5.12); the respective values in those without chronic hypertension were 1.1% (8/749) in the aspirin group and 3.9% (30/761) in the placebo group (adjusted odds ratio 0.27, 95% confidence interval, 0.12 to 0.60). In all participants with adherence of >90% the adjusted odds ratio in the aspirin group was 0.24 (95% CI 0.09 to 0.65), in the subgroup with chronic hypertension it was 2.06 (95% CI 0.40 to 10.71) and in those without chronic hypertension it was 0.05 (95% CI 0.01 to 0.41). For the complete data set the test of interaction was not significant at the 5% level (p=0.055), but in those with adherence >90%, after adjustment for multiple comparisons, the interaction was significant at the 5% level (p=0.0019). Conclusions: The beneficial effect of aspirin in the prevention of preterm preeclampsia may not apply in pregnancies with chronic hypertension. There was no evidence of heterogeneity in the aspirin effect in subgroups defined according to maternal characteristics and obstetrical history

Screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation

Objective: To examine the performance of screening for early-, preterm- and term-preeclampsia (PE) at 11 13 weeks’ gestation by maternal factors and combinations of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PLGF) and serum pregnancy associated plasma protein A (PAPP A). Methods The data for this study were derived from three previously reported prospective non intervention screening studies at 11+0 – 13+6 weeks’ gestation in a combined total of 61,174 singleton pregnancies, including 1,770 (2.9%) that developed PE. Bayes theorem was used to combine the prior distribution of the gestational age at delivery with PE, obtained from maternal characteristics, with various combinations of biomarker multiple of the median (MoM) values to derive the p patient specific risks of delivery with PE at <37 weeks’ gestation. The performance of such screening was estimated. Results In pregnancies that develop ed PE , compared to those without PE, the MoM values of UtA-PI and MAP were increased and PAPP A and PLGF were decreased and the deviation from normal was greater for early than late PE for all four biomarkers. Combined screening by maternal factors, UtA-PI, MAP and PLGF predicted 90% of early PE, 75% of preterm PE and 4 1 % of term PE, at screen positive rate of 10%; inclusion of PAPP A did not improve the performance of screening The performance of screening depended on the racial origin of the women; in screening by a combination of maternal factors, MAP, UtA-PI and PLGF and use of the risk cut off of 1 in 10 0 for PE at <37 weeks in Caucasian women, the screen positive rate was 10% and detection rates for early --, preterm and term PE were 88%, 69% and 40%, respectively. With the same method of screening and risk cut off in women of Afro Caribbean racial origin, the screen positive rate was 34% and detection rates for early --, preterm and term PE were 100%, 92% and 75%, respectively. Conclusion Screening by maternal factors and biomarkers at 11-13 weeks’ gestation can identify a high proportion of pregnancies that develop early- and preterm-PE

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Paniculitis mesentérica: experiencia en nuestro centro Mesenteric panniculitis: Experience in our center

A pesar de que se han reconocido distintos factores precipitantes en la paniculitis mesentérica, su etiología en determinados casos es incierta. Presentamos un análisis retrospectivo de 8 pacientes afectados de paniculitis mesentérica en un periodo comprendido entre mayo 2000 hasta diciembre 2006. En nuestra serie la edad media de presentación fue 63 años, siendo la mayoría de pacientes varones (proporción 3:1). Las manifestaciones clínicas más frecuentes fueron el dolor abdominal (n = 4) y la astenia (n = 4). Tres casos se presentaron como cuadro de obstrucción y tres casos presentaron antecedentes de cirugía abdominal. El antecedente más común fue el tabaquismo (5 casos eran fumadores activos y 2 exfumadores) y hubo un paciente que desarrolló un linfoma folicular en el seguimiento. Revisamos la literatura para analizar nuestros resultados y formular una hipótesis. En nuestra opinión, pensamos que debe ser analizada de forma más exhaustiva la relación entre el tabaco y sus componentes con la aparición de la enfermedad debido a la fuerte asociación encontrada en este estudio.<br>Although several etiological factors have been associated with mesenteric panniculitis, the exact etiology in some cases remains unknown. Herein, we present a retrospective analysis of 8 patients affected with this disorder performed between May 2000 and December 2006. In our series the mean age at which patients presented was 63 years. The majority of the patients were male (with a male: female ratio of 3:1). The most common clinical manifestations were abdominal pain (n = 4) and asthenia (n = 4). Three cases presented with obstructive symptoms and three had a history of abdominal surgery. Notably, seven had a background of tobacco use (five smokers and two ex-smokers) and one patient developed follicular lymphoma. A literature research was carried out to analyze our results and formulate a new hypothesis. In our opinion, we believe that the study of causal factors such as tobacco and its components is required due to the strong association found in this study

Deficiency in STAT1 Signaling Predisposes Gut Inflammation and Prompts Colorectal Cancer Development

Signal transducer and activator of transcription 1 (STAT1) is part of the Janus kinase (JAK/STAT) signaling pathway that controls critical events in intestinal immune function related to innate and adaptive immunity. Recent studies have implicated STAT1 in tumor–stroma interactions, and its expression and activity are perturbed during colon cancer. However, the role of STAT1 during the initiation of inflammation-associated cancer is not clearly understood. To determine the role of STAT1 in colitis-associated colorectal cancer (CAC), we analyzed the tumor development and kinetics of cell recruitment in wild-type WT or STAT1−/− mice treated with azoxymethane (AOM) and dextran sodium sulfate (DSS). Following CAC induction, STAT1−/− mice displayed an accelerated appearance of inflammation and tumor formation, and increased damage and scores on the disease activity index (DAI) as early as 20 days after AOM-DSS exposure compared to their WT counterparts. STAT1−/− mice showed elevated colonic epithelial cell proliferation in early stages of injury-induced tumor formation and decreased apoptosis in advanced tumors with over-expression of the anti-apoptotic protein Bcl2 at the colon. STAT1−/− mice showed increased accumulation of Ly6G+Ly6C−CD11b+ cells in the spleen at 20 days of CAC development with concomitant increases in the production of IL-17A, IL-17F, and IL-22 cytokines compared to WT mice. Our findings suggest that STAT1 plays a role as a tumor suppressor molecule in inflammation-associated carcinogenesis, particularly during the very early stages of CAC initiation, modulating immune responses as well as controlling mechanisms such as apoptosis and cell proliferation