The role of mesothelial cells in the host defence against bacteria : in vitro studies of peritonitis

The peritoneum is a serous membrane that lines both the intra-abdominal wall and the viscera contained wilhin the peritoneal cavity. Etymologically, 'peritoneum' means 'wrapped tightly around." The first description of the structure and function of the human peritoneum was given by James Doughlas in 1730. He observed that it was everywhere smooth and even and lubricated by a fiuid in order to preserve it from those inconveniences which otherwise would have followed from its continual attrilion wilh olher viscera. Human periloneum covers roughly the same surface area as the skin, approximately 2 m' in the adult. The parietal peritoneum covering the abdominal wall conslitutes about 10%, while the peritoneum covering the visceral organs, constitutes about 90% of this surface area. In males the peritoneum is completely closed, but in females it is open at the site of the uterine tubes, where the tubal peritoneum meets the non-peritonized fimbriated mucosa of the Fallopian tube. The peritoneum is a derivative of the embryological mesoderm and belongs to a distinct family of body tissues that share the same cellular composition and exhibit an identical histological architecture known as the serosa. The basic structure of the peritoneum appears to be rather simple; it is composed of a monolayer of mesothelial cells separated from the capillaries by a thin layer of loose conneclive interstilial tissue

Health care professionals overestimate the risk for locoregional recurrences after breast cancer treatment depending on their specialty

Purpose: For the implementation of personalised surveillance, it is important to create more awareness among HCPs with regard to the risk for locoregional recurrences (LRRs). The aim of this study is to evaluate the current awareness and estimations of individual risks for LRRs after completion of primary treatment for breast cancer among health care professionals (HCPs) in the Netherlands, without using any prediction tools.Methods: A cross-sectional survey was performed among 60 HCPs working in breast cancer care in seven Dutch hospitals and 25 general practitioners (GPs). The survey consisted of eleven realistic surgically treated breast cancer cases. HCPs were asked to estimate the 5-year risk for LRRs for each case, which was compared to the estimations by the INFLUENCE-nomogram using one-sample Wilcoxon tests. Differences in estimations between HCPs with different specialities were determined using Kruskal–Wallis tests and Dunn tests.Results: HCPs tended to structurally overestimate the 5-year risk for LRR on each case. Average overestimations ranged from 4.8 to 26.1%. Groups of HCPs with varying specialities differed significantly in risk estimations. GPs tended to overestimate the risk for LRRs on average the most (15.0%) and medical oncologists had the lowest average overestimation (2.7%).Conclusions: It is important to create more awareness of the risk for LRRs, which is a pre-requisite for the implementation of personalised surveillance after breast cancer. Besides education for HCPs, the use of prediction models such as the INFLUENCE-nomogram can support in estimating an objective estimate of each individual patient’s risk.</p

Anesthesia for combined liver-thoracic transplantation

The combined transplantation of a thoracic organ and the liver is performed in patients with dual-organ failure in whom survival is not expected with single-organ transplantation alone. Although uncommonly performed, the number of combined liver-lung and liver-heart transplants is increasing. Anesthetic management of this complex procedure is challenging. Major blood loss, prolonged operation time, difficult weaning of cardiopulmonary bypass and coagulation disturbances are common. Despite the complexity of surgery, the outcome is comparable to single-organ transplant

The effectiveness of personalised surveillance and aftercare in breast cancer follow-up: a systematic review

Purpose: Breast cancer follow-up (surveillance and aftercare) varies from one-size-fits-all to more personalised approaches. A systematic review was performed to get insight in existing evidence on (cost-)effectiveness of personalised follow-up.Methods: PubMed, Scopus and Cochrane were searched between 01–01-2010 and 10–10-2022 (review registered in PROSPERO:CRD42022375770). The inclusion population comprised nonmetastatic breast cancer patients ≥ 18 years, after completing curative treatment. All intervention-control studies studying personalised surveillance and/or aftercare designed for use during the entire follow-up period were included. All review processes including risk of bias assessment were performed by two reviewers. Characteristics of included studies were described.Results: Overall, 3708 publications were identified, 64 full-text publications were read and 16 were included for data extraction. One study evaluated personalised surveillance. Various personalised aftercare interventions and outcomes were studied. Most common elements included in personalised aftercare plans were treatment summaries (75%), follow-up guidelines (56%), lists of available supportive care resources (38%) and PROs (25%). Control conditions mostly comprised usual care. Four out of seven (57%) studies reported improvements in quality of life following personalisation. Six studies (38%) found no personalisation effect, for multiple outcomes assessed (e.g. distress, satisfaction). One (6.3%) study was judged as low, four (25%) as high risk of bias and 11 (68.8%) as with concerns.Conclusion: The included studies varied in interventions, measurement instruments and outcomes, making it impossible to draw conclusions on the effectiveness of personalised follow-up. There is a need for a definition of both personalised surveillance and aftercare, whereafter outcomes can be measured according to uniform standards.</p

Early Thromboembolic Stroke Risk of Postoperative Atrial Fibrillation Following Cardiac Surgery

OBJECTIVE: The authors aimed to study the association between postoperative atrial fibrillation (POAF) and thromboembolic stroke and to determine risk factors for thromboembolic stroke after cardiac surgery. DESIGN: The authors performed a secondary analysis from a randomized controlled trial (GRIP-COMPASS). The patients with thromboembolic stroke were compared with those without thromboembolic stroke, and the difference in the incidence of POAF between these groups was assessed. Odds ratios (OR) were calculated using logistic regression analyses. Brain imaging was studied for the occurrence of thromboembolic stroke during hospital admission, and POAF was monitored for seven days. To assess which characteristics were associated with occurrence of thromboembolic stroke, stepwise backward regression analysis was performed. PARTICIPANTS: All adult consecutive cardiac surgery patients admitted postoperatively to the intensive care unit. SETTING: Academic tertiary care medical center. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 910 patients included in this study, 26 patients (2.9%) had a thromboembolic stroke during hospital admission. The incidence of POAF during the first seven days after cardiac surgery in those with thromboembolic stroke was 65%, compared with 39% in those without thromboembolic stroke: adjusted OR 3.01 (95% confidence interval, 1.13-8.00). POAF, a history of peripheral vascular disease, a higher EuroSCORE, and a longer duration of surgery were associated with thromboembolic stroke. CONCLUSIONS: POAF within seven days after cardiac surgery was associated with a three-fold increased risk for a thromboembolic stroke during hospital admission. Expeditious treatment of POAF may, therefore, reduce early stroke risk after cardiac surgery

Clinical impact of molecular breast imaging as adjunct diagnostic modality in evaluation of indeterminate breast abnormalities and unresolved diagnostic concerns

Purpose Improvements in molecular breast imaging (MBI) have increased the use of MBI as adjunct diagnostic modality and alternative to MRI. We aimed to assess the value of MBI in patients with equivocal breast lesions on conventional imaging, especially in terms of its ability to rule out malignancy. Methods We selected patients who underwent MBI in addition to conventional diagnostics due to equivocal breast lesions between 2012 and 2015. All patients underwent digital mammography, target ultrasound and MBI. MBI was performed using a single-head Dilon 6800 gamma camera after administration of 600 MBq 99mTc-sestamibi. Imaging was reported according to BI-RADS classification and compared with pathology or follow-up of ≥6 months. Results Of 226 women included, pathology was obtained in 106 (47%) and (pre)malignant lesions were found in 25 (11%). Median follow-up was 5.4 years (IQR 3.9-7.1). Sensitivity was higher for MBI compared to conventional diagnostics (84% vs. 32%; P = 0.002), identifying malignancy in 21 and 6 patients, respectively, but specificity did not differ (86% vs. 81%; P = 0.161). Positive and negative predictive value were 43% and 98% for MBI and 17% and 91% for conventional diagnostics. MBI was discordant with conventional diagnostics in 68 (30%) patients and correctly changed diagnosis in 46 (20%) patients, identifying 15 malignant lesions. In subgroups with nipple discharge (N = 42) and BI-RADS 3 lesions (N = 113) MBI detected 7 of 8 occult malignancies. Conclusion MBI correctly adjusted treatment in 20% of patients with diagnostic concerns after conventional work-up, and could rule out malignancy with a high negative predictive value of 98%.</p

Driving pressure during general anesthesia for open abdominal surgery (DESIGNATION) : study protocol of a randomized clinical trial

Background Intraoperative driving pressure (Delta P) is associated with development of postoperative pulmonary complications (PPC). When tidal volume (V-T) is kept constant, Delta P may change according to positive end-expiratory pressure (PEEP)-induced changes in lung aeration. Delta P may decrease if PEEP leads to a recruitment of collapsed lung tissue but will increase if PEEP mainly causes pulmonary overdistension. This study tests the hypothesis that individualized high PEEP, when compared to fixed low PEEP, protects against PPC in patients undergoing open abdominal surgery. Methods The "Driving prESsure durIng GeNeral AnesThesIa for Open abdomiNal surgery trial" (DESIGNATION) is an international, multicenter, two-group, double-blind randomized clinical superiority trial. A total of 1468 patients will be randomly assigned to one of the two intraoperative ventilation strategies. Investigators screen patients aged >= 18 years and with a body mass index <= 40 kg/m(2), scheduled for open abdominal surgery and at risk for PPC. Patients either receive an intraoperative ventilation strategy with individualized high PEEP with recruitment maneuvers (RM) ("individualized high PEEP") or one in which PEEP of 5 cm H2O without RM is used ("low PEEP"). In the "individualized high PEEP" group, PEEP is set at the level at which Delta P is lowest. In both groups of the trial, V-T is kept at 8 mL/kg predicted body weight. The primary endpoint is the occurrence of PPC, recorded as a collapsed composite of adverse pulmonary events. Discussion DESIGNATION will be the first randomized clinical trial that is adequately powered to compare the effects of individualized high PEEP with RM versus fixed low PEEP without RM on the occurrence of PPC after open abdominal surgery. The results of DESIGNATION will support anesthesiologists in their decisions regarding PEEP settings during open abdominal surgery

Acute appendicitis: transcript profiling of blood identifies promising biomarkers and potential underlying processes

Background The diagnosis of acute appendicitis can be surprisingly difficult without computed tomography, which carries significant radiation exposure. Circulating blood cells may carry informative changes in their RNA expression profile that would signal internal infection or inflammation of the appendix. Methods Genome-wide expression profiling was applied to whole blood RNA of acute appendicitis patients versus patients with other abdominal disorders, in order to identify biomarkers of appendicitis. From a large cohort of emergency patients, a discovery set of patients with surgically confirmed appendicitis, or abdominal pain from other causes, was identified. RNA from whole blood was profiled by microarrays, and RNA levels were filtered by a combined fold-change (\u3e2) and p value (\u3c0.05). A separate set of patients, including patients with respiratory infections, was used to validate a partial least squares discriminant (PLSD) prediction model. Results Transcript profiling identified 37 differentially expressed genes (DEG) in appendicitis versus abdominal pain patients. The DEG list contained 3 major ontologies: infection-related, inflammation-related, and ribosomal processing. Appendicitis patients had lower level of neutrophil defensin mRNA (DEFA1,3), but higher levels of alkaline phosphatase (ALPL) and interleukin-8 receptor-ß (CXCR2/IL8RB), which was confirmed in a larger cohort of 60 patients using droplet digital PCR (ddPCR). Conclusions Patients with acute appendicitis have detectable changes in the mRNA expression levels of factors related to neutrophil innate defense systems. The low defensin mRNA levels suggest that appendicitis patient’s immune cells are not directly activated by pathogens, but are primed by diffusible factors in the microenvironment of the infection. The detected biomarkers are consistent with prior evidence that biofilm-forming bacteria in the appendix may be an important factor in appendicitis

Excision of both pretreatment marked positive nodes and sentinel nodes improves axillary staging after neoadjuvant systemic therapy in breast cancer

Background: Marking the axilla with radioactive iodine seed and sentinel lymph node (SLN) biopsy have been proposed for axillary staging after neoadjuvant systemic therapy in clinically node-positive breast cancer. This study evaluated the identification rate and detection of residual disease with combined excision of pretreatment-positive marked lymph nodes (MLNs) together with SLNs. Methods: This was a multicentre retrospective analysis of patients with clinically node-positive breast cancer undergoing neoadjuvant systemic therapy and the combination procedure (with or without axillary lymph node dissection). The identification rate and detection of axillary residual disease were calculated for the combination procedure, and for MLNs and SLNs separately. Results: At least one MLN and/or SLN(s) were identified by the combination procedure in 138 of 139 patients (identification rate 99·3 per cent). The identification rate was 92·8 per cent for MLNs alone and 87·8 per cent for SLNs alone. In 88 of 139 patients (63·3 per cent) residual axillary disease was detected by the combination procedure. Residual disease was shown only in the MLN in 20 of 88 patients (23 per cent) and only in the SLN in ten of 88 (11 per cent), whereas both the MLN and SLN contained residual disease in the remainder (58 of 88, 66 per cent). Conclusion: Excision of the pretreatment-positive MLN together with SLNs after neoadjuvant systemic therapy in patients with clinically node-positive disease resulted in a higher identification rate and improved detection of residual axillary disease