Prospective Study Examining Clinical Outcomes Associated with a Negative Pressure Wound Therapy System and Barker’s Vacuum Packing Technique

Background The open abdomen has become a common procedure in the management of complex abdominal problems and has improved patient survival. The method of temporary abdominal closure (TAC) may play a role in patient outcome. Methods A prospective, observational, open-label study was performed to evaluate two TAC techniques in surgical and trauma patients requiring open abdomen management: Barker’s vacuum-packing technique (BVPT) and the ABTheraTM open abdomen negative pressure therapy system (NPWT). Study endpoints were days to and rate of 30-day primary fascial closure (PFC) and 30-day all-cause mortality. Results Altogether, 280 patients were enrolled from 20 study sites. Among them, 168 patients underwent at least 48 hours of consistent TAC therapy (111 NPWT, 57 BVPT). The two study groups were well matched demographically. Median days to PFC were 9 days for NPWT versus 12 days for BVPT (p = 0.12). The 30-day PFC rate was 69 % for NPWT and 51 % for BVPT (p = 0.03). The 30-day all-cause mortality was 14 % for NPWT and 30 % for BVPT (p = 0.01). Multivariate logistic regression analysis identified that patients treated with NPWT were significantly more likely to survive than the BVPT patients [odds ratio 3.17 (95 % confidence interval 1.22–8.26); p = 0.02] after controlling for age, severity of illness, and cumulative fluid administration. Conclusions Active NPWT is associated with significantly higher 30-day PFC rates and lower 30-day all-cause mortality among patients who require an open abdomen for at least 48 h during treatment for critical illness

Modulation of hepatic PPAR expression during Ft LVS LPS-induced protection from Francisella tularensis LVS infection

<p>Abstract</p> <p>Background</p> <p>It has been shown previously that administration of <it>Francisella tularensis </it>(<it>Ft</it>) Live Vaccine Strain (LVS) lipopolysaccharide (LPS) protects mice against subsequent challenge with <it>Ft </it>LVS and blunts the pro-inflammatory cytokine response.</p> <p>Methods</p> <p>To further investigate the molecular mechanisms that underlie <it>Ft </it>LVS LPS-mediated protection, we profiled global hepatic gene expression following <it>Ft </it>LVS LPS or saline pre-treatment and subsequent <it>Ft </it>LVS challenge using Affymetrix arrays.</p> <p>Results</p> <p>A large number of genes (> 3,000) were differentially expressed at 48 hours post-infection. The degree of modulation of inflammatory genes by infection was clearly attenuated by pre-treatment with <it>Ft </it>LVS LPS in the surviving mice. However, <it>Ft </it>LVS LPS alone had a subtle effect on the gene expression profile of the uninfected mice. By employing gene set enrichment analysis, we discovered significant up-regulation of the fatty acid metabolism pathway, which is regulated by peroxisome proliferator activated receptors (PPARs).</p> <p>Conclusions</p> <p>We hypothesize that the LPS-induced blunting of pro-inflammatory response in mouse is, in part, mediated by PPARs (α and γ).</p

Inhibition of Lassa Virus Glycoprotein Cleavage and Multicycle Replication by Site 1 Protease-Adapted α1-Antitrypsin Variants

The virus family Arenaviridae includes several hemorrhagic fever causing agents such as Lassa, Guanarito, Junin, Machupo, and Sabia virus that pose a major public health concern to the human population in West African and South American countries. Current treatment options to control fatal outcome of disease are limited to the ribonucleoside analogue ribavirin, although its use has some significant limitations. The lack of effective treatment alternatives emphasizes the need for novel antiviral therapeutics to counteract these life-threatening infections. Maturation cleavage of the viral envelope glycoprotein by the host cell proprotein convertase site 1 protease (S1P) is critical for infectious virion production of several pathogenic arenaviruses. This finding makes this protease an attractive target for the development of novel anti-arenaviral therapeutics. We demonstrate here that highly selective S1P-adapted α1-antitrypsins have the potential to efficiently inhibit glycoprotein processing, which resulted in reduced Lassa virus replication. Our findings suggest that S1P should be considered as an antiviral target and that further optimization of modified α1-antitrypsins could lead to potent and specific S1P inhibitors with the potential for treatment of certain viral hemorrhagic fevers

The clinical importance of monitoring intra-abdominal pressure after ruptured abdominal aortic aneurysm repair

Aim: The aim of this paper was to review the literature on the clinical importance of monitoring intra-abdominal pressure (IAP) after ruptured abdominal aortic aneurysm (rAAA) repair. Method: The literature was searched for abdominal compartment syndrome (ACS) or intra-abdominal pressure and aortic aneurysm. Original articles were studied. Personal experiences were reported. Results: The Consensus Documents of the World Society on the Abdominal Compartment Syndrome (wsacs.org), with their definitions and guidelines, constitute an important step forward for the possibilities to study this clinical entity. Few papers were published describing the problem specifically in the patient population operated on for ruptured abdominal aortic aneurysm (rAAA). The incidence was approximately 5% when the patients were not monitored with IAP, and above 10% when IAP was monitored. The incidence seems to be similar irrespective if open or endovascular repair is performed, though comparative prospective studies were not published. Patients with intra-abdominal hypertension (IAH) or ACS have higher mortality and more complications. If IAH is recognized early conservative treatment may be effective to prevent development of ACS. After ACS has developed, surgical decompression is usually required. A proposed algorithm on how to act on different levels of IAH is presented. Conclusions: IAH/ACS is an important complication after operation on patients with rAAA. Monitoring IAP may be associated with improved outcomes

Endovascular Versus Open Repair as Primary Strategy for Ruptured Abdominal Aortic Aneurysm: A National Population-based Study

Objective/BackgroundIn randomized trials, no peri-operative survival benefit has been shown for endovascular (EVAR) repair of ruptured abdominal aortic aneurysm (rAAA) when compared with open repair. The aim of this study was to investigate the effect of primary repair strategy on early and midterm survival in a non-selected population based study.MethodsThe Swedish Vascular Registry was consulted to identify all rAAA repairs performed in Sweden in the period 2008–12. Centers with a primary EVAR strategy (treating > 50% of rAAA with EVAR) were compared with centers with a primary open repair strategy. Peri-operative outcome, midterm survival, and incidence of rAAA repair/100,000 inhabitants aged > 50 years were assessed.ResultsIn total, 1,304 patients were identified. Three primary EVAR centers (pEVARc) operated on 236 patients (74.6% EVAR). Twenty-six primary open repair centers (pORc) operated 1,068 patients (15.6% EVAR). Patients treated at pEVARc were more often referrals (28.0% vs. 5.3%; p < .01), had a higher rate of respiratory comorbidity (36.5% vs. 21.9%; p < .01), and higher pre-operative systolic blood pressure (84.3 vs. 72.3 mmHg; p < .01). There was no difference in mortality based on primary treatment strategy at 30 days (pEVARc 28.0%, n = 66; pORc 27.4%, n = 296 [p = .87]), 1 year (pEVARc 39.9%, n = 93; pORc 34.7%, n = 366 [p = .19]), or 2 years (42.1%, n = 94; 38.3%, n = 394 [p = .28]), either overall or in subgroups based on age or referral status. Overall, patients treated with EVAR were older (mean age 76.4 vs. 74.0 years; p < .01), and had a lower 30 day mortality (EVAR 21.6%, n = 74; odds ratio 29.6%, n = 288 [p = < .01]). Incidence of rAAA repair was lower in pEVARc regions (6.07, 95% confidence interval [CI] 5.01–7.13) when compared with pORc regions (8.15, 95% CI 7.64–8.66).ConclusionThere was no difference in mortality after rAAA repair among centers with a primary EVAR approach when compared with a primary open repair strategy, either peri-operatively or in the midterm. The study supports the early findings of the randomized controlled trials in a national population based setting