Risk-adjusted procedure tailoring leads to uniformly low complication rates in ventral and incisional hernia repair: a propensity score analysis and internal validation of classification criteria.

BACKGROUND: The usual approach in hernia surgery is to select the ideal repair method independent of the patient's characteristics. In the present study, we change the approach to ask which technique is best for the individual patient`s risk profile. For this, two criteria are important: does the patient need reconstruction of the abdominal wall? or does he or she need treatment of symptoms without being exposed to unnecessarily high perioperative risks? METHODS: In a heuristic selection procedure, 486 consecutive patients were classified according to their characteristics as low-risk or high-risk for postoperative complications. Low-risk patients preferentially underwent open abdominal wall reconstruction with mesh (MFR + mesh), high-risk patients mainly a bridging-mesh procedure, either by laparoscopic (Lap.-IPOM) or open approach (Open-IPOM). Primary outcome was the incidence of postoperative complications. Secondary outcome was the recurrence-free interval. The propensity score was used for covariate adjustment analyzing recurrence rate as well as postoperative complications using Cox regression and logistic regression, respectively. RESULTS: Comparison of all surgical procedures showed risk factors had no independent influence on occurrence of complications (p = 0.110). Hernial gap width was an independent factor for occurrence of complications (p = 0.002). Propensity score adjustment revealed Lap.-IPOM to have a significantly higher recurrence rate than MFR + mesh (HR 2.367, 95% CI 1.123-4.957, p = 0.024). Three or more risk factors were protective against recurrence (HR 0.454, 95% CI 0.221-0.924, p = 0.030). In the univariate Cox regression analysis for recurrence, age >50 years was a protective prognostic factor (HR 0.412, 95% CI 0.245-0.702, p = 0.002). CONCLUSIONS: The classification criteria applied were internally validated. The heuristic algorithm ensured that patients at high-risk of complications did not have a higher perioperative complication rate than patients at low-risk.

Importance of recurrence rating, morphology, hernial gap size, and risk factors in ventral and incisional hernia classification.

BACKGROUND: There is limited evidence on the natural course of ventral and incisional hernias and the results of hernia repair, what might partially be explained by the lack of an accepted classification system. The aim of the present study is to investigate the association of the criteria included in the Wuerzburg classification system of ventral and incisional hernias with postoperative complications and long-term recurrence. METHODS: In a retrospective cohort study, the data on 330 consecutive patients who underwent surgery to repair ventral and incisional hernias were analyzed. The following four classification criteria were applied: (a) recurrence rating (ventral, incisional or incisional recurrent); (b) morphology (location); (c) size of the hernial gap; and (d) risk factors. The primary endpoint was the occurrence of a recurrence during follow-up. Secondary endpoints were incidence of postoperative complications. Independent association between classification criteria, type of surgical procedures and postoperative complications was calculated by multivariate logistic regression analysis and between classification criteria, type of surgical procedures and risk of long-term recurrence by Cox regression analysis. RESULTS: Follow-up lasted a mean 47.7 ± 23.53 months (median 45 months) or 3.9 ± 1.96 years. The criterion "recurrence rating" was found as predictive factor for postoperative complications in the multivariate analysis (OR 2.04; 95 % CI 1.09-3.84; incisional vs. ventral hernia). The criterion "morphology" had influence neither on the incidence of the critical event "recurrence during follow-up" nor on the incidence of postoperative complications. Hernial gap "width" predicted postoperative complications in the multivariate analysis (OR 1.98; 95 % CI 1.19-3.29; ≤5 vs. >5 cm). Length of the hernial gap was found to be an independent prognostic factor for the critical event "recurrence during follow-up" (HR 2.05; 95 % CI 1.25-3.37; ≤5 vs. >5 cm). The presence of 3 or more risk factors was a consistent predictor for "recurrence during follow-up" (HR 2.25; 95 % CI 1.28-9.92). Mesh repair was an independent protective factor for "recurrence during follow-up" compared to suture (HR 0.53; 95 % CI 0.32-0.86). CONCLUSIONS: The ventral and incisional hernia classification of Dietz et al. employs a clinically proven terminology and has an open classification structure. Hernial gap size and the number of risk factors are independent predictors for "recurrence during follow-up", whereas recurrence rating and hernial gap size correlated significantly with the incidence of postoperative complications. We propose the application of these criteria for future clinical research, as larger patient numbers will be needed to refine the results.

ArcA and AppY antagonize IscR repression of hydrogenase-1 expression under anaerobic conditions, revealing a novel mode of O2 regulation of gene expression in Escherichia coli.

Transcription of the Escherichia coli hydrogenase-1 operon (hyaABCDEF) is increased by the transcription factors ArcA and AppY under anaerobic growth conditions. However, IscR, which represses transcription of the hyaA promoter (P(hyaA)) under aerobic conditions, was not known to repress transcription of this promoter under anaerobic conditions. Here, we report that ArcA and AppY increase P(hyaA) expression under anaerobic conditions by antagonizing IscR binding at P(hyaA), since IscR repression is observed when either ArcA or AppY is eliminated. The ability of ArcA and AppY to act as antirepressors of IscR repression of P(hyaA) depended on IscR levels, suggesting that IscR competes with ArcA and/or AppY for binding. In support of this competition model, electrophoretic mobility shift assays and DNase I footprinting showed that the ArcA and IscR binding sites overlap and that binding of ArcA and IscR is mutually exclusive. Unexpectedly, IscR with a C92A mutation (IscR-C92A), which mimics the clusterless form of the protein that is present predominantly under aerobic conditions, was a better repressor under anaerobic conditions of both P(hyaA) and a constitutive promoter containing the IscR binding site from P(hyaA) than wild-type IscR, which is predominantly in the [2Fe-2S] form under anaerobic conditions. This observation could not be explained by differences in DNA binding affinities or IscR levels, so we conclude that [2Fe-2S]-IscR is a weaker repressor of P(hyaA) than clusterless IscR. In sum, a combination of ArcA and AppY antirepression of IscR function, lower levels of IscR, and weak repression by [2Fe-2S]-IscR leads to increased P(hyaA) expression under anaerobic conditions.

Potassium channels and modulating factors of channel functions in the human myometrium.

Hexoprenaline, a beta-adrenergic agonist of clinical importance in preventing preterm labor, and the calcitonin gene-related peptide (CGRP) that is known to have receptors in the plasmalemma of myometrial cells were investigated to ascertain whether in human myometrium K+(Ca++)channels are involved in the relaxant mechanism. Small sections from the fundus and the corpus of vaginal-dissected uteri were isolated under limitation of the operation collective (age of women 35-50 years). Strips of 1-cm length were cut for isometric measurement of contraction. After an equilibration of 60 min under 10 mN tension at 37 degrees C, spontaneous activity occurred and experiments were performed. By enzymatic disaggregation with papain and collagenase single cells were isolated. Electrophysiological experiments were performed using the patch-clamp technique in the cell-attached and excised inside-out configurations. We observed K+ channels with a conductance of 158 pS between -20 and 20 mV in [K+]o/[K+]i of 5.4/140 mM with a reversal potential at about -70 mV. The channel was sensitive to the free calcium concentration on the cytoplasmic side and open probability (Po) increased with membrane depolarization. 0.5 mM ATP facing the cytoplasmic side of the patches (at 40 mV depolarization and pCa of 6) showed no inhibition. Hexoprenaline and CGRP both increased the Po of the K+ (Ca++)channels in the cell-attached mode at steady-state kinetics. Forskolin failed to be an activator of K+ (Ca++)channels. In isometric measurements of human myometrial strips spontaneous activity is suppressed by hexoprenaline 10(-5) M and CGRP 10(-7) M, but these effects are antagonized by 2 mM TEA.(ABSTRACT TRUNCATED AT 250 WORDS)