Effect of natural genetic variation on enhancer selection and function.

The mechanisms by which genetic variation affects transcription regulation and phenotypes at the nucleotide level are incompletely understood. Here we use natural genetic variation as an in vivo mutagenesis screen to assess the genome-wide effects of sequence variation on lineage-determining and signal-specific transcription factor binding, epigenomics and transcriptional outcomes in primary macrophages from different mouse strains. We find substantial genetic evidence to support the concept that lineage-determining transcription factors define epigenetic and transcriptomic states by selecting enhancer-like regions in the genome in a collaborative fashion and facilitating binding of signal-dependent factors. This hierarchical model of transcription factor function suggests that limited sets of genomic data for lineage-determining transcription factors and informative histone modifications can be used for the prioritization of disease-associated regulatory variants.

Preoperative anemia is a risk factor for poor perioperative outcomes in ventral hernia repair.

PURPOSE: Ventral hernia repairs (VHR) are among the most commonly performed operations by general surgeons. Despite advances in technology there remains high complication and readmission rates. Preoperative anemia has been linked to poor outcomes and readmission across several surgical procedures, however the link to ventral hernia repair outcomes is limited. METHODS: Utilizing the American College of Surgeons National Safety and Quality Improvement Project (NSQIP) database for years 2016-2018, a total of 115,000 patients met inclusion criteria. Using propensity matching we matched two groups of patients who underwent VHR: (1) those with preoperative anemia and (2) those with normal hemoglobin levels. Anemia criteria was set forth by the World Health Organization (WHO). RESULTS: Univariate analysis did demonstrate statistical significance in post-operative outcomes percentage of serious surgical site infection, poor renal outcomes, transfusion, and unplanned remission in those with preoperative anemia who underwent VHR. In a multivariate analysis, patients who underwent ventral hernia repair with pre-operative anemia had significantly greater odds of unplanned readmission (odds ratio 1.35, 95% confidence interval 1.16-1.57) and serious surgical site infection (odds ratio 1.35, 95% confidence interval 1.04-1.74) independent of known risk factors such as smoking, diabetes and obesity. CONCLUSIONS: Preoperative anemia is a risk factor for poor postoperative outcomes in those undergoing ventral hernia repair and should be considered when evaluating a patient for repair.

Blood ethanol and serum osmolality in the trauma patient.

The relationships between blood alcohol concentrations and both "osmolar difference" (measured serum osmolality minus expected serum osmolality calculated from serum sodium, serum potassium, blood urea, and blood glucose concentrations) and total serum osmolality have been investigated in severely traumatized patients. Osmolar difference was found to be more strongly correlated to blood alcohol concentration than serum osmolality; however, the error in the slopes of the regression lines was essentially identical (approximately 17%). Consequently, indirect estimations of blood alcohol concentrations by calculating osmolar difference do not improve the accuracy obtained by the estimation by measurement of serum osmolality alone. It appears that the production of unidentified osmoles in traumatized patients significantly influences all indirect calculation of blood alcohol by osmometry. A direct determination of blood alcohol should be made whenever possible.

Sequential serum complement (C3) and immunoglobulin levels in shock/trauma patients developing acute fulminant systemic sepsis.

The complement system has been implicated in the physiopathology of septic shock. Since infection is a major cause of death in trauma patients, we examined daily serum C3 and immunoglobulin levels in all victims of major trauma during a 3-month interval. Sixteen patients developed acute systemic sepsis 3-15 days after admission. For all variables the lowest values occurred shortly after hospital admission, during or just after fluid resuscitation. Thereafter, the serum C3 and immunoglobulin concentrations gradually returned to the normal ranges, despite the onset of fulminant systemic sepsis. Except for IgM, the occurrence of hypotension during sepsis did not affect the recovery patterns of the measured variables. In the five patients experiencing hypotension, serum IgM dropped transiently but resumed its normalization trend after the restoration of adequate perfusion pressure. In the three nonsurvivors there was no reduction in the serum C3 or immunoglobulin levels prior to death. These data do not support a role for C3 or the immunoglobulins in the pathogenesis of acute fulminant clinical sepsis. On the contrary, the behavior of these substances during severe sepsis is more consistent with protective host defense functions.

Coordinated teamwork in California industrial rehabilitation.

This article describes a case study of an industrially produced hand injury that exemplifies the coordination and teamwork involved in vocational rehabilitation in the California Workers' Compensation system. This patient required multiple tendon and nerve transplant operations done with microsurgical techniques, hand therapy for functional and sensory retraining, job analysis, vocational evaluation, labor market survey, work-hardening experience, and an on-the-job training program to effect a successful outcome. An overview of the current status of the California Workers' Compensation system and current insurance perspectives are discussed.

Alcohol intoxication and serum osmolality.

The relation between serum osmolality and blood-alcohol was studied prospectively in 565 acute trauma patients. The two measurements were closely correlated. It is therefore possible to estimate the blood-alcohol from serum osmolality to assist in the clinical management of acutely injured patients.