Hypoxia modulates the barrier and coagulant function of cultured bovine endothelium. Increased monolayer permeability and induction of procoagulant properties.

Exposure of cultured endothelium to environments with low concentrations of oxygen, in the range of those observed in pathophysiologic hypoxemic states in vivo, compromises cellular barrier and coagulant function. An atmosphere with PO2 approximately 14 mm Hg was not lethally toxic to endothelial cultures, but cells became larger and exhibited small intercellular gaps. At low oxygen concentrations, passage of macromolecular tracers through hypoxic endothelial monolayers was accelerated in a time- and dose-dependent manner, presumably by a paracellular pathway via the gaps. Cell surface coagulant properties of the endothelium were also perturbed. At PO2 approximately 14 mm Hg thrombomodulin antigen and functional activity on the cell surface were diminished by 80-90%, and Northern blots demonstrated suppression of thrombomodulin mRNA. The decrease in thrombomodulin was twice as great compared with the general decline in total protein synthesis in hypoxia. In addition, expression of a direct Factor X activator developed under hypoxic conditions; the activator was membrane-associated and expressed on the surface of intact cultures, Ca-dependent, inhibited by HgCl2 but not PMSF, and had Km approximately 25 micrograms/ml for the substrate at pH 7.4. Synthesis of the activator was blocked by inclusion of cycloheximide, but not warfarin, in the culture medium. These results demonstrate that endothelial function is perturbed in a selective manner in the presence of low concentrations of oxygen, providing insights into mechanisms which may contribute to vascular dysfunction in hypoxemic states.     

Clinician vs mathematical statistical models: which is better at predicting an abnormal chest radiograph finding in injured patients?

Objective

The purpose of this study was to determine if statistical models for prediction of chest injuries would outperform the clinician's (MD) ability to identify injured patients at risk for a thoracic injury diagnosed by chest radiograph (CXR).

Design

A prospective observational study was done during a 12-month period.

Setting

The study was conducted in a level I trauma center.

Patients

Injured patients meeting trauma team activation criteria were enrolled to the study.

Interventions

Physical examination findings by a clinician were interpreted and CXR was performed.

Outcome measures

The accuracy of 2 mathematical models is compared against the accuracy of clinician's clinical judgment in predicting an injury by CXR. Two newly constructed multivariate models, binary logistic regression (LR) and classification and regression tree (CaRT) analysis, are compared to previously published data of clinician clinical assessment of probability of thoracic injury identified by CXR.

Results

Data for 757 patients were analyzed. Classification and regression tree analysis developed a stepwise decision tree to determine which signs/symptoms were indicative of an abnormal CXR finding.The sensitivity (CaRT, 36.6%; LR, 36.3%; MD, 58.7%), specificity (CaRT, 98.3%; LR, 98.2%; MD, 96.4%), and error rates (CaRT, 0.93; LR, 0.94; MD, 0.82) show that the mathematical decision aids are less sensitive and risk more misclassification compared to clinician judgment in predicting an injury by CXR.

Conclusion

Clinician judgment was superior to mathematical decision aids for predicting an abnormal CXR finding in injured patients with chest trauma.     

Liver Perfusion Changes Occurring During Pancreatic Islet Engraftment: A Dynamic Contrast‐Enhanced Magnetic Resonance Study

The aim of this study was to investigate liver microvascular adaptation following the intraportal infusion of pancreatic islets (pancreatic islet transplantation [islet‐tx]) in diabetic patients using dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI). DCE‐MRI was performed before and 7 days after islet‐tx in six diabetic patients. Initial area under curve (AUC60) and volume transfer coefficient (Ktrans) were assessed as markers of liver perfusion. Clinical and metabolic monthly follow‐up was performed in all patients, considering fasting C‐peptide and β‐score as main indices of graft function. High variability in the response of liver microvasculature to islet infusion was observed: two patients showed a significant reduction in liver perfusion after transplantation (pt.2: AUC60 = ?23.4%, Ktrans = ?31.7%; pt.4: AUC60 = ?23.7%, Ktrans = ?27.9%); three patients did not show any significant variation of liver perfusion and one patient showed a significant increase (pt.3: AUC60 = +31%, Ktrans = +42.8%). Interestingly, a correlation between DCE‐MRI parameters and indices of graft function was observed and, in particular, both patients with DCE‐MRI evidence of posttransplantation liver perfusion reduction experienced premature graft failure. Our preliminary study demonstrated that DCE‐MRI may identify different adaptive responses of liver microvasculature in patients submitted to islet‐tx. These different responses could have an impact on islet engraftment, although reported findings need confirmation from larger studies.

     

Pancreatic surgery is a safe teaching model for tutoring residents in the setting of a high-volume academic hospital: a retrospective analysis of surgical and pathological outcomes

BackgroundAcademic hospitals must train future surgeons, but whether residents could negatively affect the outcomes of major procedures is a matter of concern. The aim of this study is to assess if pancreatic surgery is a safe teaching model.MethodsOutcomes of 1230 major pancreatic resections performed at a high-volume pancreatic teaching hospital between 2015 and 2018 were compared according to the first surgeon type, attending vs resident.ResultsResidents performed a selection of 132 (16%) pancreaticoduodenectomies (PD) and 46 (11%) distal pancreatectomies (DP). For PD, pancreatic fistula (25% vs 0, p < 0.001), biliary fistula (7.1% vs 3.5%, p = 0.04) and operative time (400 vs 390 min, p < 0.001) were lower for residents but post-pancreatectomy hemorrhage was higher (20.5% vs 13% p = 0.024). For DP, pancreatic fistula rate was lower for residents (31.7% vs 17.5% p = 0.046). There was no difference in terms of lymph nodes retrieval both for PDs and DPs, while the R1 resections were more frequent among PDs performed by attending surgeons (31.5% vs 15.7%, p = 0.023).ConclusionThe active participation of residents does not negatively affect outcomes of major pancreatic resections in a high-volume center. By means of case selection and continuous tutoring, pancreatic surgery represents a safe and valid teaching model.     

US and MR imaging findings to detect placental adhesion spectrum (PAS) in patients with placenta previa: a comparative systematic study

Purpose

To compare the performance US and MR in identifying placental adhesion spectrum (PAS) in placenta previa (PP) and to establish a potential method of image interpretation.

Methods

US and MR examinations of 51 patients with PP were selected. The presence of imaging signs commonly used to detect PAS was assessed. Penalized logistic regression was performed considering histology as standard of reference; only signs statistically significant (p < 0.05) were considered for ROC and multivariate analysis. The probability of PAS according to the presence of US and/or MR signs was then assessed.

Results

At univariate analysis, loss of retroplacental clear space, myometrial thinning (MT) and placenta lacunar spaces on US, intraplacental dark bands (IDBs), focal interruption of myometrial border (FIMB) and abnormal vascularity (AV) on MR were statistically significant (p < 0.01). Three diagnostic methods for PAS were then developed for both US and MR when at least one (Method 1), two (Method 2) or three (Method 3) imaging signs occurred, respectively. Method 2 for MR showed a significantly (p < 0.05) higher accuracy (91%) compared to the other methods. When MR IDBs and AV as well as IDBs and FIMB were present in combination with US MT the probability of PAS increased from 75 to 90% and from 80 to 91%, respectively.

Conclusion

MR demonstrated a higher diagnostic accuracy than US to detect PAS. However, since the combination of MR and US signs could improve the probability to detect PAS, a complementary diagnostic role of these techniques could be considered.

     

Mice reconstituted with DNA polymerase beta-deficient fetal liver cells are able to mount a T cell-dependent immune response and mutate their Ig genes normally

The ubiquitously expressed, error-prone DNA polymerase beta (polbeta) plays a role in base excision repair, and the involvement of this molecule in the nonhomologous end joining (NHEJ) process of DNA repair has recently been demonstrated in yeast. Polbeta-deficient mice are not viable, and studies on conditional mutants revealed a competitive disadvantage of polbeta(-/-) vs. wild-type cells. We show here that polbeta-deficient mice survive up to day 18.5 postcoitum, but die perinatally; a circumstance that allowed the investigation of a potential role of polbeta in lymphocyte development by transfer of fetal liver cells (FLC) derived from polbeta(-/-) embryos into lethally irradiated hosts. FLC transfers using mutant cells lead to an almost normal reconstitution of the lymphocyte compartment, indicating that polbeta-deficiency does not prevent V(D)J recombination, which is known to employ factors of the NHEJ pathway. Mice reconstituted with polbeta(-/-) FLC mount a normal T cell-dependent immune response against the hapten (4-hydroxy-3-nitrophenyl) acetyl (NP). Moreover, germinal center B cells from NP-immunized reconstituted mice show normal levels and patterns of somatic point mutations in their rearranged antibody genes, demonstrating that polbeta is not critically involved in somatic hypermutation.