Antiviral activity of gliotoxin, gentian violet and brilliant green against Nipah and Hendra virus in vitro

Background: Using a recently described monolayer assay amenable to high throughput screening format for the identification of potential Nipah virus and Hendra virus antivirals, we have partially screened a low molecular weight compound library (8,000 compounds) directly against live virus infection and identified twenty eight promising lead molecules. Initial single blind screens were conducted with 10 M compound in triplicate with a minimum efficacy of 90% required for lead selection. Lead compounds were then further characterised to determine the median efficacy (IC), cytotoxicity (CC) and the in vitro therapeutic index in live virus and pseudotype assay formats. Results: While a number of leads were identified, the current work describes three commercially available compounds: brilliant green, gentian violet and gliotoxin, identified as having potent antiviral activity against Nipah and Hendra virus. Similar efficacy was observed against pseudotyped Nipah and Hendra virus, vesicular stomatitis virus and human parainfluenza virus type 3 while only gliotoxin inhibited an influenza A virus suggesting a non-specific, broad spectrum activity for this compound. Conclusion: All three of these compounds have been used previously for various aspects of anti-bacterial and anti-fungal therapy and the current results suggest that while unsuitable for internal administration, they may be amenable to topical antiviral applications, or as disinfectants and provide excellent positive controls for future studies

Consensus document on controversial issues in the treatment of complicated skin and skin-structure infections

Summary Background Complicated skin and skin-structure infections (cSSSI), including surgical site infections (SSI), cellulitis, and abscesses, have been extensively studied, but controversial issues still exist. Controversial issues The aim of this GISIG (Gruppo Italiano di Studio sulle Infezioni Gravi) working group – a panel of multidisciplinary experts – was to define recommendations for the following controversial issues: (1) What is the efficacy of topical negative pressure wound treatment as compared to standard of care in the treatment of severe surgical site infections, i.e., deep infections, caused by Gram-positive microorganisms? (2) Which are the most effective antibiotic therapies in the treatment of cSSSI, including SSI, due to methicillin-resistant staphylococci? Results are presented and discussed. Methods A systematic literature search using the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and www.clinicaltrials.gov databases of randomized controlled trials and/or non-randomized studies was performed. A matrix was created to extract evidence from original studies using the CONSORT method to evaluate randomized clinical trials and the Newcastle–Ottawa Quality Assessment Scale for case–control studies, longitudinal cohorts, and retrospective studies. The GRADE method was used for grading quality of evidence. An analysis of the studies published between 1990 and 2008 is presented and discussed in detail

Perforated peptic ulcer (PPU) treatment: an Italian nationwide propensity score-matched cohort study investigating laparoscopic vs open approach

BackgroundPerforated peptic ulcer (PPU) remain a surgical emergency accounting for 37% of all peptic ulcer-related deaths. Surgery remains the standard of care. The benefits of laparoscopic approach have been well-established even in the elderly. However, because of inconsistent results with specific regard to some technical aspects of such technique surgeons questioned the adoption of laparoscopic approach. This leads to choose the type of approach based on personal experience. The aim of our study was to critically appraise the use of the laparoscopic approach in PPU treatment comparing it with open procedure.MethodsA retrospective study with propensity score matching analysis of patients underwent surgical procedure for PPU was performed. Patients undergoing PPU repair were divided into: Laparoscopic approach (LapA) and Open approach (OpenA) groups and clinical-pathological features of patients in the both groups were compared.ResultsA total of 453 patients underwent PPU simple repair. Among these, a LapA was adopted in 49% (222/453 patients). After propensity score matching, 172 patients were included in each group (the LapA and the OpenA). Analysis demonstrated increased operative times in the OpenA [OpenA: 96.4 +/- 37.2 vs LapA 88.47 +/- 33 min, p = 0.035], with shorter overall length of stay in the LapA group [OpenA 13 +/- 12 vs LapA 10.3 +/- 11.4 days p = 0.038]. There was no statistically significant difference in mortality [OpenA 26 (15.1%) vs LapA 18 (10.5%), p = 0.258]. Focusing on morbidity, the overall rate of 30-day postoperative morbidity was significantly lower in the LapA group [OpenA 67 patients (39.0%) vs LapA 37 patients (21.5%) p = 0.002]. When stratified using the Clavien-Dindo classification, the severity of postoperative complications was statistically different only for C-D 1-2.ConclusionsBased on the present study, we can support that laparoscopic suturing of perforated peptic ulcers, apart from being a safe technique, could provide significant advantages in terms of postoperative complications and hospital stay

WSES-AAST guidelines: management of inflammatory bowel disease in the emergency setting

Background Despite the current therapeutic options for the treatment of inflammatory bowel disease, surgery is still frequently required in the emergency setting, although the number of cases performed seems to have decreased in recent years. The World Society of Emergency Surgery decided to debate in a consensus conference of experts, the main pertinent issues around the management of inflammatory bowel disease in the emergent situation, with the need to provide focused guidelines for acute care and emergency surgeons. Method A group of experienced surgeons and gastroenterologists were nominated to develop the topics assigned and answer the questions addressed by the Steering Committee of the project. Each expert followed a precise analysis and grading of the studies selected for review. Statements and recommendations were discussed and voted at the Consensus Conference of the 6th World Society of Emergency Surgery held in Nijmegen (The Netherlands) in June 2019. Conclusions Complicated inflammatory bowel disease requires a multidisciplinary approach because of the complexity of this patient group and disease spectrum in the emergency setting, with the aim of obtaining safe surgery with good functional outcomes and a decreasing stoma rate where appropriate.Peer reviewe

Operative management of acute abdomen after bariatric surgery in the emergency setting: the OBA guidelines

Background: Patients presenting with acute abdominal pain that occurs after months or years following bariatric surgery may present for assessment and management in the local emergency units. Due to the large variety of surgical bariatric techniques, emergency surgeons have to be aware of the main functional outcomes and long-term surgical complications following the most performed bariatric surgical procedures. The purpose of these evidence-based guidelines is to present a consensus position from members of the WSES in collaboration with IFSO bariatric experienced surgeons, on the management of acute abdomen after bariatric surgery focusing on long-term complications in patients who have undergone laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass. Method: A working group of experienced general, acute care, and bariatric surgeons was created to carry out a systematic review of the literature following the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) and to answer the PICO questions formulated after the Operative management in bariatric acute abdomen survey. The literature search was limited to late/long-term complications following laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass. Conclusions: The acute abdomen after bariatric surgery is a common cause of admission in emergency departments. Knowledge of the most common late/long-term complications (> 4 weeks after surgical procedure) following sleeve gastrectomy and Roux-en-Y gastric bypass and their anatomy leads to a focused management in the emergency setting with good outcomes and decreased morbidity and mortality rates. A close collaboration between emergency surgeons, radiologists, endoscopists, and anesthesiologists is mandatory in the management of this group of patients in the emergency setting

Gastro-intestinal emergency surgery: Evaluation of morbidity and mortality. Protocol of a prospective, multicenter study in Italy for evaluating the burden of abdominal emergency surgery in different age groups. (The GESEMM study)

Gastrointestinal emergencies (GE) are frequently encountered in emergency department (ED), and patients can present with wide-ranging symptoms. more than 3 million patients admitted to US hospitals each year for EGS diagnoses, more than the sum of all new cancer diagnoses. In addition to the complexity of the urgent surgical patient (often suffering from multiple co-morbidities), there is the unpredictability and the severity of the event. In the light of this, these patients need a rapid decision-making process that allows a correct diagnosis and an adequate and timely treatment. The primary endpoint of this Italian nationwide study is to analyze the clinicopathological findings, management strategies and short-term outcomes of gastrointestinal emergency procedures performed in patients over 18. Secondary endpoints will be to evaluate to analyze the prognostic role of existing risk-scores to define the most suitable scoring system for gastro-intestinal surgical emergency. The primary outcomes are 30-day overall postoperative morbidity and mortality rates. Secondary outcomes are 30-day postoperative morbidity and mortality rates, stratified for each procedure or cause of intervention, length of hospital stay, admission and length of stay in ICU, and place of discharge (home or rehabilitation or care facility). In conclusion, to improve the level of care that should be reserved for these patients, we aim to analyze the clinicopathological findings, management strategies and short-term outcomes of gastrointestinal emergency procedures performed in patients over 18, to analyze the prognostic role of existing risk-scores and to define new tools suitable for EGS. This process could ameliorate outcomes and avoid futile treatments. These results may potentially influence the survival of many high-risk EGS procedure

Predictors of choice of initial antifungal treatment in intraabdominal candidiasis

Intraabdominal candidiasis (IAC) is the second most frequent form of invasive candidiasis, and is associated with high mortality rates. This study aims to identify current practices in initial antifungal treatment (IAT) in a real-world scenario and to define the predictors of the choice of echinocandins or azoles in IAC episodes. Secondary analysis was performed of a multinational retrospective cohort at 13 teaching hospitals in four countries (Italy, Greece, Spain and Brazil), over a 3-year period (2011\u20132013). IAC was identified in 481 patients, 323 of whom received antifungal therapy (classified as the treatment group). After excluding 13 patients given amphotericin B, the treatment group was further divided into the echinocandin group (209 patients; 64.7%) and the azole group (101 patients; 32.3%). Median APACHE II scores were significantly higher in the echinocandin group (p 0.013), but IAT did not differ significantly with regard to the Candida species involved. Logistic multivariate stepwise regression analysis, adjusted for centre effect, identified septic shock (adjusted OR (aOR) 1.54), APACHE II > 15 (aOR 1.16) and presence in surgical ward at diagnosis (aOR 1.16) as the top three independent variables associated with an empirical echinocandin regimen. No differences in 30-day mortality were observed between groups. Echinocandin regimen was the first choice for IAT in patients with IAC. No statistical differences in mortality were observed between regimens, but echinocandins were administered to patients with more severe disease. Some disagreements were identified between current clinical guidelines and prescription of antifungals for IAC at the bedside, so further educational measures are required to optimize therapies

Metabolic Syndrome (MetS), Systemic Inflammatory Response Syndrome (SIRS), and Frailty: Is There any Room for Good Outcome in the Elderly Undergoing Emergency Surgery?

Background: Patients with MetS or SIRS experience higher rates of mortality and morbidity, across both cardiac and noncardiac surgery. Frailty assessment has acquired increasing importance in recent years as it predisposes elderly patients to a worse outcome. The aim of our study was to investigate the influence of MetS, SIRS, and with or without frailty on elderly patients undergoing emergency surgical procedures. Methods: We analyzed data of all patients with nonmalignant diseases requiring an emergency surgical procedure from January 2017 to December 2020. The occurrence of MetS was identified using modified definition criteria used by the NCEP-ATP III Expert Panel: obesity, hypertension, diabetes, or if medication for high triglycerides or for low HDL cholesterol was taken. Systemic inflammatory response syndrome (SIRS) was evaluated according to the original consensus study (Sepsis-1). The frailty profile was investigated by the 5-modified Frailty Index (5-mFI) and the Emergency Surgery Frailty Index (EmSFI). Postoperative complications have been reported and categorized according to the Clavien–Dindo (C–D) classification system. Morbidity and mortality have been mainly considered as the 30-day standard period definition. Results: Of the 2,318 patients included in this study, 1,010 (43.6%) fulfilled the criteria for MetS (MetsG group). Both 5-Items score and EmsFI showed greater fragility in patients with MetS. All patients with MetS showed more frequently a CACI index greater than 6. The occurrence of SIRS was higher in MetSG. LOS was longer in patients with MetS (MetSG 11.4 ± 12 days vs. n-MetSG 10.5 ± 10.2 days, p = 0.046). MetSG has a significantly higher rate of morbidity (353 (35.%) vs. 385 (29.4%), p = 0.005). The mortality rate in patients with MetS (98/1010, 10%) was similar to that in patients without it (129/1308, 10%). Considering patients with MetS who developed SIRS and those who had frailty or both, the occurrence of these conditions was associated with a higher rate of morbidity and mortality. Conclusion: Impact of MetS and SIRS on elderly surgical patient outcomes has yet to be fully elucidated. The present study showed a 43.6% incidence of MetS in the elderly population. In conclusion, age per se should be not considered anymore as the main variable to estimate patient outcomes, while MetS and Frailty should have always a pivotal role

Source control in emergency general surgery: WSES, GAIS, SIS-E, SIS-A guidelines

Intra-abdominal infections (IAI) are among the most common global healthcare challenges and they are usually precipitated by disruption to the gastrointestinal (GI) tract. Their successful management typically requires intensive resource utilization, and despite the best therapies, morbidity and mortality remain high. One of the main issues required to appropriately treat IAI that differs from the other etiologies of sepsis is the frequent requirement to provide physical source control. Fortunately, dramatic advances have been made in this aspect of treatment. Historically, source control was left to surgeons only. With new technologies non-surgical less invasive interventional procedures have been introduced. Alternatively, in addition to formal surgery open abdomen techniques have long been proposed as aiding source control in severe intra-abdominal sepsis. It is ironic that while a lack or even delay regarding source control clearly associates with death, it is a concept that remains poorly described. For example, no conclusive definition of source control technique or even adequacy has been universally accepted. Practically, source control involves a complex definition encompassing several factors including the causative event, source of infection bacteria, local bacterial flora, patient condition, and his/her eventual comorbidities. With greater understanding of the systemic pathobiology of sepsis and the profound implications of the human microbiome, adequate source control is no longer only a surgical issue but one that requires a multidisciplinary, multimodality approach. Thus, while any breach in the GI tract must be controlled, source control should also attempt to control the generation and propagation of the systemic biomediators and dysbiotic influences on the microbiome that perpetuate multi-system organ failure and death. Given these increased complexities, the present paper represents the current opinions and recommendations for future research of the World Society of Emergency Surgery, of the Global Alliance for Infections in Surgery of Surgical Infection Society Europe and Surgical Infection Society America regarding the concepts and operational adequacy of source control in intra-abdominal infections

The weekend effect on the provision of Emergency Surgery before and during the COVID-19 pandemic: case–control analysis of a retrospective multicentre database

Introduction: The concept of “weekend effect”, that is, substandard healthcare during weekends, has never been fully demonstrated, and the different outcomes of emergency surgical patients admitted during weekends may be due to different conditions at admission and/or different therapeutic approaches. Aim of this international audit was to identify any change of pattern of emergency surgical admissions and treatments during weekends. Furthermore, we aimed at investigating the impact of the COVID-19 pandemic on the alleged “weekend effect”. Methods: The database of the CovidICE-International Study was interrogated, and 6263 patients were selected for analysis. Non-trauma, 18+ yo patients admitted to 45 emergency surgery units in Europe in the months of March–April 2019 and March–April 2020 were included. Demographic and clinical data were anonymised by the referring centre and centrally collected and analysed with a statistical package. This study was endorsed by the Association of Italian Hospital Surgeons (ACOI) and the World Society of Emergency Surgery (WSES). Results: Three-quarters of patients have been admitted during workdays and only 25.7% during weekends. There was no difference in the distribution of gender, age, ASA class and diagnosis during weekends with respect to workdays. The first wave of the COVID pandemic caused a one-third reduction of emergency surgical admission both during workdays and weekends but did not change the relation between workdays and weekends. The treatment was more often surgical for patients admitted during weekends, with no difference between 2019 and 2020, and procedures were more often performed by open surgery. However, patients admitted during weekends had a threefold increased risk of laparoscopy-to-laparotomy conversion (1% vs. 3.4%). Hospital stay was longer in patients admitted during weekends, but those patients had a lower risk of readmission. There was no difference of the rate of rescue surgery between weekends and workdays. Subgroup analysis revealed that interventional procedures for hot gallbladder were less frequently performed on patients admitted during weekends. Conclusions: Our analysis revealed that demographic and clinical profiles of patients admitted during weekends do not differ significantly from workdays, but the therapeutic strategy may be different probably due to lack of availability of services and skillsets during weekends. The first wave of the COVID-19 pandemic did not impact on this difference