Abstract Methods The American Society of Anesthesiologists Physical Status classification system (ASA PS) is a method of characterizing patient operative risk on a scale of 1–5, where 1 is normal ...health and 5 is moribund. Every anesthesiologist is trained in this measure, and it is performed before every procedure in which a patient undergoes anesthesia. We measured the independent predictive value of ASA-PS for complications and mortality in the ACS-NSQIP database by multivariate regression. We conducted analogous regressions after standardizing ASA-PS to control for interprocedural variations in risk in the overall model and sub-analyses by surgical specialty and the most common procedures. Results For 2,297,629 cases (2005–2012; median age 55, min = 16, max>90 90 and above are coded as 90+), at increasing levels of ASA-PS (2–5), odds ratios (OR's) from 2.05 to 63.25 (complications, p < 0.001) and 5.77–2011.92 (mortality, p < 0.001) were observed, with non-overlapping 95% confidence intervals. Standardization of ASA-PS (OR = 1.426 per standard deviation above the mean ASA-PS per procedure, p < .001) and subgroup analyses yielded similar results. Discussion ASA PS was not only found to be associated with increased morbidity and mortality, but independently predictive when controlling for other comorbidities. Even after standardization based on procedure type, increases in ASA predicted significant increases in complication rates for morbidity and mortality post-operatively. Conclusions ASA PS has strong, independent associations with post-operative medical complications and mortality across procedures. This capability, along with its simplicity, makes it a valuable prognostic metric.
The microbiota is known to modulate the host response to influenza infection through as-yet-unclear mechanisms. We hypothesized that components of the microbiota exert effects through type I ...interferon (IFN), a hypothesis supported by analysis of influenza in a gain-of-function genetic mouse model. Here we show that a microbially associated metabolite, desaminotyrosine (DAT), protects from influenza through augmentation of type I IFN signaling and diminution of lung immunopathology. A specific human-associated gut microbe, Clostridium orbiscindens, produced DAT and rescued antibiotic-treated influenza-infected mice. DAT protected the host by priming the amplification loop of type I IFN signaling. These findings show that specific components of the enteric microbiota have distal effects on responses to lethal infections through modulation of type I IFN.
Colonic wound repair is an orchestrated process, beginning with barrier re-establishment and followed by wound channel formation and crypt regeneration. Elevated levels of prostaglandin E2 (PGE2) ...promote barrier re-establishment; however, we found that persistently elevated PGE2 hinders subsequent repair phases. The bacterial metabolite deoxycholate (DCA) promotes transition through repair phases via PGE2 regulation. During barrier re-establishment, DCA levels are locally diminished in the wound, allowing enhanced PGE2 production and barrier re-establishment. However, during transition to the wound channel formation phase, DCA levels increase to inhibit PGE2 production and promote crypt regeneration. Altering DCA levels via antibiotic treatment enhances PGE2 levels but impairs wound repair, which is rescued with DCA treatment. DCA acts via its receptor, farnesoid X receptor, to inhibit the enzyme cPLA2 required for PGE2 synthesis. Thus, colonic wound repair requires temporally regulated signals from microbial metabolites to coordinate host-associated signaling cascades.
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•PGE2 promotes barrier re-establishment but inhibits crypt regeneration in the colon•DCA and PGE2 levels are temporally and reciprocally regulated during colonic repair•DCA acts via its receptor FXR to inhibit PGE2 production and promote crypt regeneration•DCA/FXR inhibits cPLA2 involved in PGE2 synthesis to suppress PGE2 production
Jain et al. discover that temporal regulation of a bacterial metabolite, deoxycholate, orchestrates phases of colonic repair. In the first phase, deoxycholate is depleted to allow for barrier re-establishment; it re-emerges in the second phase to promote crypt regeneration. Mechanistically, deoxycholate promotes these transitions by modulating PGE2 levels.
There is a major unmet clinical need to identify pathways in inflammatory bowel disease (IBD) to classify patient disease activity, stratify patients that will benefit from targeted therapies such as ...anti-tumor necrosis factor (TNF), and identify new therapeutic targets. In this study, we conducted global transcriptome analysis to identify IBD-related pathways using colon biopsies, which highlighted the coagulation gene pathway as one of the most enriched gene sets in patients with IBD. Using this gene-network analysis across 14 independent cohorts and 1800 intestinal biopsies, we found that, among the coagulation pathway genes, plasminogen activator inhibitor-1 (PAI-1) expression was highly enriched in active disease and in patients with IBD who did not respond to anti-TNF biologic therapy and that PAI-1 is a key link between the epithelium and inflammation. Functionally, PAI-1 and its direct target, the fibrinolytic protease tissue plasminogen activator (tPA), played an important role in regulating intestinal inflammation. Intestinal epithelial cells produced tPA, which was protective against chemical and mechanical-mediated colonic injury in mice. In contrast, PAI-1 exacerbated mucosal damage by blocking tPA-mediated cleavage and activation of anti-inflammatory TGF-β, whereas the inhibition of PAI-1 reduced both mucosal damage and inflammation. This study identifies an immune-coagulation gene axis in IBD where elevated PAI-1 may contribute to more aggressive disease.
Many American hospitals will soon face readmission penalties deducted from Medicare reimbursements, which will place further scrutiny on techniques that may offer reduced postoperative morbidity. We ...aimed to perform the first multi-institutional study using the National Surgical Quality Improvement Program (NSQIP) database, to compare predictors of readmission within cohorts of open radical retropubic prostatectomy (RRP) and robot-assisted laparoscopic radical prostatectomy (RALRP) in a contemporary nationwide series of radical prostatectomy.
All patients who underwent radical prostatectomy in 2011 were identified in the NSQIP database using procedural codes. As no patients in the analysis underwent LRP, patients were grouped as RRP or RALRP for analysis. Perioperative variables were analyzed using chi-squared and Student's t-tests as appropriate. Multiple logistic regression was used to identify readmission risk factors.
Of 5471 patient cases analyzed, 4374 (79.9%) and 1097 (20.1%) underwent RALRP and RRP, respectively. RRP and RALRP cohorts experienced different readmission rates (5.47% vs 3.48%, respectively; p=0.002). In addition, RRP experienced a higher rate of overall complications than RALRP (23.25% vs 5.62%, respectively; p<0.001), but not higher rates of reoperation (1.09% vs 0.96%, respectively; p=0.689). Overall predictors of readmission included operative time, dyspnea, and RRP or RALRP procedure type. Current smoking and patient age were predictive of readmission for RRP only, while dyspnea was predictive of readmission following RALRP only.
This is the first multi-institutional retrospective study that examines readmission rates and procedural intracohort predictors of readmission for RRP in the contemporary United States. We report a significant difference in postoperative complication and readmission rates in RRP compared with RALRP. Further prospective analysis is warranted.
Summary
Enteropathogenic Escherichia coli (EPEC) use a type 3 secretion system (T3SS) for injection of effectors into host cells and intestinal colonization. Here, we demonstrate that the multicargo ...chaperone CesT has two strictly conserved tyrosine phosphosites, Y152 and Y153 that regulate differential effector secretion in EPEC. Conservative substitution of both tyrosine residues to phenylalanine strongly attenuated EPEC type 3 effector injection into host cells, and limited Tir effector mediated intimate adherence during infection. EPEC expressing a CesT Y152F variant were deficient for NleA effector expression and exhibited significantly reduced translocation of NleA into host cells during infection. Other effectors were observed to be dependent on CesT Y152 for maximal translocation efficiency. Unexpectedly, EPEC expressing a CesT Y153F variant exhibited significantly enhanced effector translocation of many CesT‐interacting effectors, further implicating phosphosites Y152 and Y153 in CesT functionality. A mouse infection model of intestinal disease using Citrobacter rodentium revealed that CesT tyrosine substitution variants displayed delayed colonization and were more rapidly cleared from the intestine. These data demonstrate genetically separable functions for tandem tyrosine phosphosites within CesT. Therefore, CesT via its C‐terminal tyrosine phosphosites, has relevant roles beyond typical type III secretion chaperones that interact and stabilize effector proteins.
Pathogens with type III secretion systems (T3SS) absolutely require dedicated chaperone proteins to mediate efficient effector protein injection into host cells during infection. In this study, we implicate tandem tyrosine phosphosites of CesT in differentially regulating effector secretion and contributing to intestinal disease. These findings expand the functional importance of CesT in context of bacterial pathogenesis, revealing an unexpected phosphosite specificity for a T3SS chaperone.
Venous thromboembolism in reconstructive pelvic surgery Mueller, Margaret G., MD; Pilecki, Matthew A., BA; Catanzarite, Tatiana, MD ...
American journal of obstetrics and gynecology,
11/2014, Letnik:
211, Številka:
5
Journal Article
Recenzirano
Objective We sought to determine the incidence and risk factors for venous thromboembolism (VTE) in women undergoing reconstructive pelvic surgery (RPS). Study Design Using the American College of ...Surgeons National Surgical Quality Improvement Program registry, we identified patients who underwent RPS from 2006 through 2010 based on Current Procedural Terminology codes. We defined 2 cohorts: women with any RPS performed, with concomitant surgery from other specialties allowed (RPS + other), and women whose only procedure was RPS. VTE was defined as deep vein thrombosis or pulmonary embolism diagnosed within 30 days of surgery. Demographic characteristics, comorbidities, and operative characteristics were extracted from the database. Variables were analyzed using χ2 tests and Student t tests for categorical and continuous variables. We performed a multiple logistic regression to control for confounding variables. Results In all, 20,687 women underwent RPS + other, with 69 cases of VTE for a rate of 0.3%. Multivariate analysis demonstrated predictors for postoperative VTE including inpatient hospital status (odds ratio OR, 7.69; P < .001), higher American Society of Anesthesiology Physical Status classification (OR, 2.70; P < .001), and emergency intervention (OR, 3.65; P = .008). When women undergoing only RPS were analyzed, there were 14 cases of VTE, with an incidence of 0.1% and the only specific predictor for postoperative VTE was length of stay ( P < .037). Conclusion The incidence of VTE following RPS is very low, but it is increased in women undergoing concomitant surgeries. Patients undergoing inpatient surgery with higher American Society of Anesthesiology Physical Status classifications and requiring emergency intervention were at highest risk for VTE.
Citrobacter rodentium is an attaching and effacing mouse pathogen that models enteropathogenic and enterohemorrhagic Escherichia coli in humans. The complement system is an important innate defense ...mechanism; however, only scant information is available about the role of complement proteins during enteric infections. In this study, we examined the impact of the lack of properdin, a positive regulator of complement, in C. rodentium-induced colitis. Following infection, properdin knockout (P(KO)) mice had increased diarrhea and exacerbated inflammation combined with defective epithelial cell-derived IL-6 and greater numbers of colonizing bacteria. The defect in the mucosal response was reversed by administering exogenous properdin to P(KO) mice. Then, using in vitro and in vivo approaches, we show that the mechanism behind the exacerbated inflammation of P(KO) mice is due to a failure to increase local C5a levels. We show that C5a directly stimulates IL-6 production from colonic epithelial cells and that inhibiting C5a in infected wild-type mice resulted in defective epithelial IL-6 production and exacerbated inflammation. These outcomes position properdin early in the response to an infectious challenge in the colon, leading to complement activation and C5a, which in turn provides protection through IL-6 expression by the epithelium. Our results unveil a previously unappreciated mechanism of intestinal homeostasis involving complement, C5a, and IL-6 during bacteria-triggered epithelial injury.
Abstract Introduction Although breast reconstruction following mastectomy plays a role in the psychological impact of breast cancer, only one in three women undergo reconstruction. Few ...multi-institutional studies have compared complication profiles of reconstructive patients to non-reconstructive. Methods Using the National Surgical Quality Improvement database, all patients undergoing mastectomy from 2006 to 2010, with or without reconstruction, were identified and risk-stratified using propensity scored quintiles. The incidence of complications and comorbidities were compared. Results Of 37,723 mastectomies identified, 30% received immediate breast reconstruction. After quintile matching for comorbidities, complications rates between reconstructive and non-reconstructives were similar. This trend was echoed across all quintiles, except in the sub-group with highest comorbidities. Here, the reconstructive patients had significantly more complications than the non-reconstructive (22.8% versus 7.0%, p < 0.001). Conclusion Immediate breast reconstruction is a well-tolerated surgical procedure. However, in patients with high comorbidities, surgeons must carefully counterbalance surgical risks with psychosocial benefits to maximize patient outcomes. Level of evidence Level 3
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