Do Patients with Penetrating Abdominal Stab Wounds Require Laparotomy?

Background: The optimal management of hemodynamically stable asymptomatic patients with anterior abdominal stab wounds (AASWs) remains controversial. The goal is to identify and treat injuries in a safe cost-effective manner. Common evaluation strategies are local wound exploration (LWE), diagnostic peritoneal lavage (DPL), serial clinical assessment (SCAs) and computed tomography (CT) imaging. Making a decision about the right time to operate on a patient with a penetrating abdominal stab wound, especially those who have visceral evisceration, is a continuing challenge. Objectives: Until the year 2010, our strategy was emergency laparotomy in patients with penetrating anterior fascia and those with visceral evisceration. This survey was conducted towards evaluating the results of emergency laparotomy. So, better management can be done in patients with penetrating abdominal stab wounds. Patients and Methods: This retrospective cross-sectional study was performed on patients with abdominal penetrating trauma who referred to Al- Zahra hospital in Isfahan, Iran from October 2000 to October 2010. It should be noted that patients with abdominal blunt trauma, patients under 14 years old, those with lateral abdomen penetrating trauma and patients who had unstable hemodynamic status were excluded from the study. Medical records of patients were reviewed and demographic and clinical data were collected for all patients including: age, sex, mechanism of trauma and the results of LWE and laparotomy. Data were analyzed with PASW v.20 software. All data were expressed as mean ± SD. The distribution of nominal variables was compared using the Chi-squared test. Also diagnostic index for LWE were calculated. A two-sided P value less than 0.05 was considered to be statistically significant. Results: During the 10 year period of the study, 1100 consecutive patients with stab wounds were admitted to Al-Zahra hospital Isfahan, Iran. In total, about 150 cases had penetrating traumas in the anterior abdomen area. Sixty-three (42%) patients were operated immediately due to shock, visceral evisceration or aspiration of blood via a nasogastric tube on admission. Organ injury was seen in 78% of patients with visceral evisceration. Among these 87 cases, 29 patients’ (33.3%) anterior fascia was not penetrated in LWE. So, they were observed for several hours and discharged from the hospital without surgery. While for the remaining 58 patients (66.6%), whose LWE detected penetration of anterior abdominal fascia, laparotomy was performed which showed visceral injuries in 11 (18%) cases. Conclusions: All in all, 82 percent of laparotomies in patients with penetrated anterior abdominal fascia without visceral evisceration, who had no signs of peritoneal irritation, were negative. So, we recommended further evaluation in these patients. However, visceral evisceration is an indication for exploratory laparotomy, since in our study; the majority of patients had organ damages

Hypoxia Inducible Factor 1: A Urinary Biomarker of Kidney Disease.

Identifying noninvasive biomarkers of kidney disease is valuable for diagnostic and therapeutic purposes. Hypoxia inducible factor 1 (HIF-1) expression is known to be elevated in the kidneys in several renal disease pathologies. We hypothesized that the urinary HIF-1a mRNA level may be a suitable biomarker for expression of this protein in chronic kidney disease (CKD). We compared HIF-1a mRNA levels from urine pellets of CKD and healthy subjects. To ensure that urinary HIF-1a mRNA is of kidney origin, we examined colocalization of HIF-1a mRNA with two kidney specific markers in urine cells. We found that HIF-1a mRNA is readily quantifiable in urine pellets and its expression was significantly higher in CKD patients compared with healthy adults. We also showed that the urinary HIF-1a mRNA comes primarily from cells of renal origin. Our data suggest that urinary HIF-1a mRNA is a potential biomarker in CKD and can be noninvasively assessed in patients

Novel Structurally Designed Vaccine for S. aureus α-Hemolysin: Protection against Bacteremia and Pneumonia

Staphylococcus aureus (S. aureus) is a human pathogen associated with skin and soft tissue infections (SSTI) and life threatening sepsis and pneumonia. Efforts to develop effective vaccines against S. aureus have been largely unsuccessful, in part due to the variety of virulence factors produced by this organism. S. aureus alpha-hemolysin (Hla) is a pore-forming toxin expressed by most S. aureus strains and reported to play a key role in the pathogenesis of SSTI and pneumonia. Here we report a novel recombinant subunit vaccine candidate for Hla, rationally designed based on the heptameric crystal structure. This vaccine candidate, denoted AT-62aa, was tested in pneumonia and bacteremia infection models using S. aureus strain Newman and the pandemic strain USA300 (LAC). Significant protection from lethal bacteremia/sepsis and pneumonia was observed upon vaccination with AT-62aa along with a Glucopyranosyl Lipid Adjuvant-Stable Emulsion (GLA-SE) that is currently in clinical trials. Passive transfer of rabbit immunoglobulin against AT-62aa (AT62-IgG) protected mice against intraperitoneal and intranasal challenge with USA300 and produced significant reduction in bacterial burden in blood, spleen, kidney, and lungs. Our Hla-based vaccine is the first to be reported to reduce bacterial dissemination and to provide protection in a sepsis model of S. aureus infection. AT62-IgG and sera from vaccinated mice effectively neutralized the toxin in vitro and AT62-IgG inhibited the formation of Hla heptamers, suggesting antibody-mediated neutralization as the primary mechanism of action. This remarkable efficacy makes this Hla-based vaccine a prime candidate for inclusion in future multivalent S. aureus vaccine. Furthermore, identification of protective epitopes within AT-62aa could lead to novel immunotherapy for S. aureus infection

30-day morbidity and mortality of sleeve gastrectomy, Roux-en-Y gastric bypass and one anastomosis gastric bypass: a propensity score-matched analysis of the GENEVA data

Background: There is a paucity of data comparing 30-day morbidity and mortality of sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and one anastomosis gastric bypass (OAGB). This study aimed to compare the 30-day safety of SG, RYGB, and OAGB in propensity score-matched cohorts. Materials and methods: This analysis utilised data collected from the GENEVA study which was a multicentre observational cohort study of bariatric and metabolic surgery (BMS) in 185 centres across 42 countries between 01/05/2022 and 31/10/2020 during the Coronavirus Disease-2019 (COVID-19) pandemic. 30-day complications were categorised according to the Clavien–Dindo classification. Patients receiving SG, RYGB, or OAGB were propensity-matched according to baseline characteristics and 30-day complications were compared between groups. Results: In total, 6770 patients (SG 3983; OAGB 702; RYGB 2085) were included in this analysis. Prior to matching, RYGB was associated with highest 30-day complication rate (SG 5.8%; OAGB 7.5%; RYGB 8.0% (p = 0.006)). On multivariate regression modelling, Insulin-dependent type 2 diabetes mellitus and hypercholesterolaemia were associated with increased 30-day complications. Being a non-smoker was associated with reduced complication rates. When compared to SG as a reference category, RYGB, but not OAGB, was associated with an increased rate of 30-day complications. A total of 702 pairs of SG and OAGB were propensity score-matched. The complication rate in the SG group was 7.3% (n = 51) as compared to 7.5% (n = 53) in the OAGB group (p = 0.68). Similarly, 2085 pairs of SG and RYGB were propensity score-matched. The complication rate in the SG group was 6.1% (n = 127) as compared to 7.9% (n = 166) in the RYGB group (p = 0.09). And, 702 pairs of OAGB and RYGB were matched. The complication rate in both groups was the same at 7.5 % (n = 53; p = 0.07). Conclusions: This global study found no significant difference in the 30-day morbidity and mortality of SG, RYGB, and OAGB in propensity score-matched cohorts

30-Day morbidity and mortality of bariatric metabolic surgery in adolescence during the COVID-19 pandemic – The GENEVA study

Background: Metabolic and bariatric surgery (MBS) is an effective treatment for adolescents with severe obesity. Objectives: This study examined the safety of MBS in adolescents during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This was a global, multicentre and observational cohort study of MBS performed between May 01, 2020, and October 10,2020, in 68 centres from 24 countries. Data collection included in-hospital and 30-day COVID-19 and surgery-specific morbidity/mortality. Results: One hundred and seventy adolescent patients (mean age: 17.75 ± 1.30 years), mostly females (n = 122, 71.8%), underwent MBS during the study period. The mean pre-operative weight and body mass index were 122.16 ± 15.92 kg and 43.7 ± 7.11 kg/m2, respectively. Although majority of patients had pre-operative testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 146; 85.9%), only 42.4% (n = 72) of the patients were asked to self-isolate pre-operatively. Two patients developed symptomatic SARS-CoV-2 infection post-operatively (1.2%). The overall complication rate was 5.3% (n = 9). There was no mortality in this cohort. Conclusions: MBS in adolescents with obesity is safe during the COVID-19 pandemic when performed within the context of local precautionary procedures (such as pre-operative testing). The 30-day morbidity rates were similar to those reported pre-pandemic. These data will help facilitate the safe re-introduction of MBS services for this group of patients

Structurally designed attenuated subunit vaccines for S. aureus LukS-PV and LukF-PV confer protection in a mouse bacteremia model.

Previous efforts towards S. aureus vaccine development have largely focused on cell surface antigens to induce opsonophagocytic killing aimed at providing sterile immunity, a concept successfully applied to other Gram-positive pathogens such as Streptococcus pneumoniae. However, these approaches have largely failed, possibly in part due to the remarkable diversity of the staphylococcal virulence factors such as secreted immunosuppressive and tissue destructive toxins. S. aureus produces several pore-forming toxins including the single subunit alpha hemolysin as well as bicomponent leukotoxins such as Panton-Valentine leukocidin (PVL), gamma hemolysins (Hlg), and LukED. Here we report the generation of highly attenuated mutants of PVL subunits LukS-PV and LukF-PV that were rationally designed, based on an octameric structural model of the toxin, to be deficient in oligomerization. The attenuated subunit vaccines were highly immunogenic and showed significant protection in a mouse model of S. aureus USA300 sepsis. Protection against sepsis was also demonstrated by passive transfer of rabbit immunoglobulin raised against LukS-PV. Antibodies to LukS-PV inhibited the homologous oligomerization of LukS-PV with LukF-PV as well heterologous oligomerization with HlgB. Importantly, immune sera from mice vaccinated with the LukS mutant not only inhibited the PMN lytic activity produced by the PVL-positive USA300 but also blocked PMN lysis induced by supernatants of PVL-negative strains suggesting a broad protective activity towards other bicomponent toxins. These findings strongly support the novel concept of an anti-virulence, toxin-based vaccine intended for prevention of clinical S. aureus invasive disease, rather than achieving sterile immunity. Such a multivalent vaccine may include attenuated leukotoxins, alpha hemolysin, and superantigens

Structural analysis of Hla.

<p>(<b>A</b>) The relative topology of 1–62 and 1–62(GGG)–(223–236) AT constructs on the protein surface of a subunit from the 7AHL heptameric hemolysin crystal structure. The protein surface for the 1–62 segment is colored green, the 223–236 sequence colored dark green, and the remaining structure colored purple. (<b>B</b>) Topology of the secondary structural elements in α-hemolysin for peptide segments examined in this study.</p

Neutralization of Hla with AT62-IgG.

<p>100 ng of purified alpha toxin was pre-incubated at RT with different concentration of polyclonal antibody ranging from 500 µg/ml to 0.5 µg/ml and then incubated with 2% rabbit blood at 37°C for 30 min. The suspension was centrifuged and hemolysis was measured at OD_{416 nm}.</p