Combination of Proactive Molecular Risk Classifier for Endometrial cancer (ProMisE) with sonographic and demographic characteristics in preoperative prediction of recurrence or progression of endometrial cancer.

OBJECTIVE: To evaluate the ability of demographic and sonographic variables and the Proactive Molecular Risk Classifier for Endometrial cancer (ProMisE) classification to predict preoperatively tumor recurrence or progression in women with endometrial cancer. METHODS: The study included 339 women with histologically confirmed endometrial cancer who underwent expert transvaginal ultrasound in a single center before surgery as part of the prospective International Endometrial Tumor Analysis 4 study or who were evaluated using the same protocol. The tumors were classified according to histotype, FIGO (International Federation of Gynecology and Obstetrics) grade and FIGO stage. In addition, molecular analysis was performed for classification into the four ProMisE subtypes: polymerase-ϵ exonuclease domain mutations (POLE EDM), mismatch repair proteins deficiency (MMR-D), protein 53 wild type (p53 wt) and protein 53 abnormal (p53 abn). Demographic and preoperative sonographic characteristics, tumor recurrence or progression and survival were compared between the ProMisE subgroups. Cox regression analysis was used to identify prognostic factors associated with recurrence or progression, using univariable models to study crude associations and multivariable models to study adjusted associations. Logistic regression and receiver-operating-characteristics (ROC)-curve analysis were used to assess the predictive ability of the preoperative prognostic factors regarding recurrence or progression of cancer within 3 years after surgery, and to compare their predictive ability to that of the European Society for Medical Oncology (ESMO) preoperative (based on depth of myometrial invasion, histotype and grade) and postoperative (based on histotype, grade, surgical stage and lymphovascular space invasion) risk classifications. In a separate subanalysis, cases were stratified according to ProMisE p53 abn status (present vs absent) and sonographic tumor size (anteroposterior (AP) diameter < 2 cm vs ≥ 2 cm). RESULTS: Median follow-up time from surgery was 58 months (interquartile range, 48-71 months; range, 0-102 months). Recurrence or progression of cancer occurred in 51/339 (15%) women, comprising 14% of those with MMR-D, 8% of those with POLE EDM, 9% of those with p53 wt and 45% of those with p53 abn ProMisE subtype. On multivariable analysis, age, waist circumference, ProMisE subtype and tumor extension and AP diameter on ultrasound were associated with tumor recurrence or progression. A multivariable model comprising ProMisE subtype, age, waist circumference and sonographic tumor extension and size (area under the ROC curve (AUC), 0.89 (95% CI, 0.85-0.93)) had comparable ability to predict tumor recurrence/progression to that of a multivariable model comprising histotype, grade, age, waist circumference and sonographic tumor extension and size (AUC, 0.88 (95% CI, 0.83-0.92)), and better predictive ability than both the preoperative (AUC, 0.74 (95% CI, 0.67-0.82); P < 0.01) and postoperative (AUC, 0.79 (95% CI, 0.72-0.86); P < 0.01) ESMO risk classifications. Women with a combination of non-p53 abn subtype and tumor size < 2 cm (164/339 (48%)) had a very low risk (1.8%) of tumor recurrence or progression. CONCLUSIONS: The combination of demographic characteristics, sonographic findings and ProMisE subtype had better preoperative predictive ability for tumor recurrence or progression than did the ESMO classification, supporting their use in the preoperative risk stratification of women with endometrial cancer. The combination of p53 status with ultrasound tumor size has the potential to identify preoperatively a large group of women with a very low risk of recurrence or progression. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. - Legal Statement: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Is out-of-hours cholecystectomy for acute cholecystitis associated with complications?

BACKGROUND: Existing data on the safety of out-of-hours cholecystectomy are conflicting. The aim of this study was to investigate whether out-of-hours cholecystectomy for acute cholecystitis is associated with a higher risk for complications compared with surgery during office hours. METHODS: This was a population-based cohort study. The Swedish Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography Register (GallRiks) was used to investigate the association between out-of-hours cholecystectomy for acute cholecystitis and complications developing within 30 days. Data from patients who underwent cholecystectomy between 2006 and 2017 were collected. Out-of-hours surgery was defined as surgery commencing between 19.00 and 07.00 hours on weekdays, or any time at weekends (Friday 19.00 hours to Monday 07.00 hours). Multivariable logistic regression analysis was used to assess the risk of complications, with time of procedure as independent variable. The proportion of open procedures and proportion of procedures exceeding 120 min were also analysed. Adjustments were made for sex, age, ASA grade, time between admission and surgery, and hospital-specific features. RESULTS: Of 11 153 procedures included, complications occurred within 30 days in 1573 patients (14·1 per cent). The adjusted odds ratio (OR) for complications for out-of-hours versus office-hours surgery was 1·12 (95 per cent c.i. 0·99 to 1·28). The adjusted OR for procedures completed as open surgery was 1·39 (1·25 to 1·54), and that for operating time exceeding 120 min was 0·63 (0·58 to 0·69). CONCLUSION: Out-of-hours complications may relate to patient factors and the higher proportion of open procedures.

ANTECEDENTES: Los datos existentes sobre la seguridad de la colecistectomía fuera del horario laboral son discordantes. El objetivo de este estudio fue investigar si la colecistectomía para el tratamiento de la colecistitis aguda realizada fuera del horario laboral se asocia con un mayor riesgo de complicaciones en comparación con la cirugía efectuada durante el horario laboral. MÉTODOS: Se trata de un estudio de cohortes de base poblacional. Se utilizó el registro Swedish Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography Register (GallRiks) para examinar la asociación entre la colecistectomía por colecistitis aguda realizada fuera del horario laboral y las complicaciones a los 30 días. Se recogieron los datos de los pacientes en los que se realizó una colecistectomía entre 2006 y 2017. Se definió como cirugía fuera del horario laboral aquella realizada entre las 19:00 y las 07:00 de lunes a viernes y en cualquier momento durante los fines de semana (de viernes 19:00 a lunes 07:00) Se realizó un análisis de regresión logística multivariable para evaluar el riesgo de complicaciones, considerando la hora de la cirugía como variable independiente. También se analizó el porcentaje de intervenciones por vía abierta y el de aquellas cuya duración excedió de los 120 minutos. Se realizaron ajustes por sexo, edad, puntuación ASA, días desde el ingreso hasta la cirugía y características específicas del hospital. RESULTADOS: Se produjeron 1.573 (14,1%) complicaciones en las 11.153 intervenciones incluidas. La razón de oportunidades, odds ratio (OR) ajustada para las complicaciones comparando la cirugía fuera del horario laboral con la cirugía dentro del horario laboral, fue de 1,12 (i.c. del 95% 0,99-1,28). La OR ajustada para los procedimientos realizado por vía abierta fue de 1,39 (1,25-1,54). La OR ajustada para el tiempo operatorio > 120 minutos fue de 0,63 (0,58-0,69). CONCLUSIÓN: Las complicaciones que suceden en la cirugía efectuada fuera del horario laboral es más probable que se deban a factores relacionados con el paciente que con la hora del día en que se practica la cirugía. Debe tenerse en cuenta que las intervenciones realizadas por vía abierta fuera del horario laboral tienen una mayor morbilidad.

Slow-release vaginal insert of misoprostol versus orally administrated solution of misoprostol for the induction of labour in primiparous term pregnant women: a randomised controlled trial.

OBJECTIVE: To compare the World Health Organization (WHO) recommended orally administrated dosage of misoprostol (25 µg) with a vaginal slow-release (7 µg/hour) insert of misoprostol regarding time from induction to delivery and safety of the method. DESIGN: Open label, Randomised controlled trial (RCT). SETTING: Delivery ward at a secondary referral hospital in Stockholm, Sweden, from 1 October 2016 to 21 February 2018. POPULATION: One hundred and ninety-six primiparous women with singletons in cephalic presentation at ≥37 weeks of gestation and with a Bishop score of ≤4. METHODS: Women were randomised to an oral solution of misoprostol (Cytotec® n = 99) or vaginal slow-release misoprostol (Misodel® [MVI] n = 97). MAIN OUTCOME MEASURES: Primary outcome: time from induction to vaginal delivery. SECONDARY OUTCOMES: mode of delivery; proportion of vaginal deliveries within 24 hours (VD24); neonates with an Apgar score of <7 at 5 minutes; pH < 7.10; postpartum haemorrhage (PPH) of >1000 ml; hyperstimulation; and women's delivery experience (VAS). RESULTS: There was no difference in the time to delivery [corrected] (median 21.1 hours in the MVI group and 23.2 hours in the oral group; Kaplan-Mayer log rank P = 0.31). There was no difference regarding the proportion of VD24 (50.5 versus 55.7%, P = 0.16). Hyperstimulation with non-reassuring cardiotocography (CTG) was more common in the MVI group (14.4 versus 3.0%, P < 0.01). Terbutaline (Bricanyl® ) was used more often for hyperstimulation in the MVI group (22.7 versus 4.0%, P < 0.01). There was no difference in the numbers of children admitted to the neonatal intensive care unit (NICU). CONCLUSIONS: Vaginal delivery after induction of labour (IOL) with slow-release misoprostol did not result in a shorter time from induction to vaginal delivery, compared with oral misoprostol solution, but was associated with a higher risk for hyperstimulation and fetal distress. There were no differences in mode of delivery or neonatal outcome. TWEETABLE ABSTRACT: IOL with MVI was similar to oral solution of misoprostol but hyperstimulation and fetal distress were more common.

The effect of carbamazepine on warfarin anticoagulation: a register-based nationwide cohort study involving the Swedish population.

BACKGROUND: There are data indicating that the interaction between warfarin and carbamazepine results in decreased warfarin efficacy. However, the evidence on the magnitude of and interindividual differences in susceptibility to this interaction has remained scarce. OBJECTIVES: To investigate the effect of carbamazepine on warfarin anticoagulation and warfarin maintenance doses by the use of data from three nationwide registries. PATIENTS/METHODS: In a retrospective cohort study including 166 patients, warfarin doses were compared 2-4 weeks before and 10-13 weeks after initiation of cotreatment with carbamazepine. In addition, warfarin doses and International Normalized Ratio (INR) values were calculated week-by-week during cotreatment. Data on prescribed warfarin doses and INR measurements were obtained from two large Swedish warfarin registers. Data on carbamazepine use were retrieved from the Swedish Prescribed Drug Register. RESULTS: The average warfarin doses were 49% (95% confidence interval 43-56) higher during carbamazepine treatment. The INR decreased upon carbamazepine initiation, and subtherapeutic INR levels were observed in 79% of all patients during the fifth week of cotreatment. Warfarin maintenance dose increases exceeding 50% and 100% were observed in 59% and 17% of patients, respectively. CONCLUSIONS: Four of five warfarin-treated patients in whom cotreatment with carbamazepine was initiated experienced subtherapeutic anticoagulative effect within 3-5 weeks. The warfarin dose was subsequently increased by 49%, a change that differed widely between patients. In order to avoid thrombosis and ischemic stroke, carbamazepine initiation should be accompanied by close INR monitoring to better meet the anticipated increase in dose demand.

Surgical correction of shoulder rotation deformity in brachial plexus birth palsy: long-term results in 118 patients.

We present the long-term results of open surgery for internal shoulder rotational deformity in brachial plexus birth palsy (BPBP). From 1997 to 2005, 207 patients (107 females, 100 males, mean age 6.2 (0.6 to 34)) were operated on with subscapularis elongation and/or latissimus dorsi to infraspinatus transfer. Incongruent shoulder joints were relocated. The early results of these patients has been reported previously. We analysed 118 (64 females, 54 males, mean age 15.1 (7.6 to 34)) of the original patient cohort at a mean of 10.4 years (7.0 to 15.1) post-operatively. A third of patients with relocated joints had undergone secondary internal rotational osteotomy of the humerus. A mixed effects models approach was used to evaluate the effects of surgery on shoulder rotation, abduction, and the Mallet score. Independent factors were time (pre-and post-surgery), gender, age, joint category (congruent, relocated, relocated plus osteotomy) and whether or not a transfer had been performed. Data from a previously published short-term evaluation were reworked in order to obtain pre-operative values. The mean improvement in external rotation from pre-surgery to the long-term follow-up was 66.5° (95% confidence interval (CI) 61.5 to 71.6). The internal rotation had decreased by a mean of 22.6° (95% CI -18.7 to -26.5). The mean improvement in the three-grade aggregate Mallet score was 3.1 (95% CI 2.7 to 3.4), from 8.7 (95% CI 8.4 to 9.0) to 11.8 (11.5 to 12.1). Our results show that open subscapularis elongation achieves good long-term results for patients with BPBP and an internal rotation contracture, providing lasting joint congruency and resolution of the trumpet sign, but with a moderate mean loss of internal rotation.