Interaction analysis of subgroup effects in randomized trials: the essential methodological points.

Subgroup analysis aims to identify subgroups (usually defined by baseline/demographic characteristics), who would (or not) benefit from an intervention under specific conditions. Often performed post hoc (not pre-specified in the protocol), subgroup analyses are prone to elevated type I error due to multiple testing, inadequate power, and inappropriate statistical interpretation. Aside from the well-known Bonferroni correction, subgroup treatment interaction tests can provide useful information to support the hypothesis. Using data from a previously published randomized trial where a p value of 0.015 was found for the comparison between standard and Hemopatch® groups in (the subgroup of) 135 patients who had hand-sewn pancreatic stump closure we first sought to determine whether there was interaction between the number and proportion of the dependent event of interest (POPF) among the subgroup population (patients with hand-sewn stump closure and use of Hemopatch®), Next, we calculated the relative excess risk due to interaction (RERI) and the "attributable proportion" (AP). The p value of the interaction was p = 0.034, the RERI was - 0.77 (p = 0.0204) (the probability of POPF was 0.77 because of the interaction), the RERI was 13% (patients are 13% less likely to sustain POPF because of the interaction), and the AP was - 0.616 (61.6% of patients who did not develop POPF did so because of the interaction). Although no causality can be implied, Hemopatch® may potentially decrease the POPF after distal pancreatectomy when the stump is closed hand-sewn. The hypothesis generated by our subgroup analysis requires confirmation by a specific, randomized trial, including only patients undergoing hand-sewn closure of the pancreatic stump after distal pancreatectomy.Trial registration: INS-621000-0760.

Practical approach to acute pancreatitis: from diagnosis to the management of complications.

The purpose of this review is to provide a practical guide for the clinical care of patients with acute pancreatitis (AP) from the management of the early phases of disease to the treatment of local complications. AP is one of the most frequent causes of gastroenterological admission in emergency departments. It is characterized by a dynamic and unpredictable course and in its most severe forms, is associated with organ dysfunction and/or local complications, requiring intensive care with significant morbidity and mortality. Initial therapy includes adequate fluid resuscitation, nutrition, analgesia, and when necessary critical care support. In recent years, the development of minimally invasive tailored treatments for local complications, such as endoscopic drainage, has improved patients' acceptance and outcomes. Despite this, the management of AP remains a challenge for clinicians. The present review was conducted by the authors, who formulated specific questions addressing the most critical and current aspects of the clinical course of AP with the aim of providing key messages.

European society for trauma and emergency surgery member-identified research priorities in emergency surgery: a roadmap for future clinical research opportunities.

BACKGROUND: European Society for Trauma and Emergency Surgery (ESTES) is the European community of clinicians providing care to the injured and critically ill surgical patient. ESTES has several interlinked missions - (1) the promotion of optimal emergency surgical care through networked advocacy, (2) promulgation of relevant clinical cognitive and technical skills, and (3) the advancement of scientific inquiry that closes knowledge gaps, iteratively improves upon surgical and perioperative practice, and guides decision-making rooted in scientific evidence. Faced with multitudinous opportunities for clinical research, ESTES undertook an exercise to determine member priorities for surgical research in the short-to-medium term; these research priorities were presented to a panel of experts to inform a 'road map' narrative review which anchored these research priorities in the contemporary surgical literature. METHODS: Individual ESTES members in active emergency surgery practice were polled as a representative sample of end-users and were asked to rank potential areas of future research according to their personal perceptions of priority. Using the modified eDelphi method, an invited panel of ESTES-associated experts in academic emergency surgery then crafted a narrative review highlighting potential research priorities for the Society. RESULTS: Seventy-two responding ESTES members from 23 countries provided feedback to guide the modified eDelphi expert consensus narrative review. Experts then crafted evidence-based mini-reviews highlighting knowledge gaps and areas of interest for future clinical research in emergency surgery: timing of surgery, inter-hospital transfer, diagnostic imaging in emergency surgery, the role of minimally-invasive surgical techniques and Enhanced Recovery After Surgery (ERAS) protocols, patient-reported outcome measures, risk-stratification methods, disparities in access to care, geriatric outcomes, data registry and snapshot audit evaluations, emerging technologies interrogation, and the delivery and benchmarking of emergency surgical training. CONCLUSIONS: This manuscript presents the priorities for future clinical research in academic emergency surgery as determined by a sample of the membership of ESTES. While the precise basis for prioritization was not evident, it may be anchored in disease prevalence, controversy around aspects of current patient care, or indeed the identification of a knowledge gap. These expert-crafted evidence-based mini-reviews provide useful insights that may guide the direction of future academic emergency surgery research efforts.

Clinical Frailty Score is a good predictor of postoperative mortality in patients undergoing open abdomen surgery: a multicenter retrospective cohort study.

BACKGROUND: Open Abdomen (OA) is gaining popularity in damage control surgery (DCS) but there is not an absolute prognostic score to identify patients that may benefit from it. Our study investigates the correlation between the clinical frailty scale score (CFSS) and postoperative morbidity and mortality in patients undergoing OA. METHODS: Patients ≥65 yo undergoing OA in two referral centres between 2015 and 2020 were included and stratified according to CFSS in non-frail (NF), frail (F) and highly-frail (HF). The primary endpoint was 30-day mortality. Secondary endpoints were postoperative morbidity and 1- year survival. RESULTS: One hundred and thirty-six patients were included: 35 NF (25.7%), 56 F (41.2%), 45 HF (33.1%). Average age 76.8. The 73.5% of cases were non-traumatic diseases with no difference in preoperative characteristics. 95 (71.4%) had one complication, 26 NF (74.3%), 34 F (63.2%), 35 HF (77.8%) (P=0.301) and 59.4% had a complication with a CD≥3, 57.1% NF, 56.6% F and 64.4 HF. The 30-day mortality was 32.4%, higher in HF (46.7%) and F (30.4%) compared to NF (17.1%, P=0.018). The Overall 1-year survival was 41% (SE ±4) with statistically significant difference between HF vs. NF and HF vs. F (P=0.009 and P=0.029, respectively). In the univariate analysis, the only significant prognostic factor impacting mortality was CFSS, with HF having an HR of 1.948 (95% CI 1.097-3.460, P=0.023). CONCLUSIONS: When OA is a surgical option, frail patients should not be precluded, while HF should be carefully evaluated. The CFSS might be a good prognostic score for patients that may safely benefit from OA.

Spread and feasibility of non-operative management (NOM) of traumatic splenic injuries in adults: a national survey.

In hemodynamically stable adults sustaining a splenic trauma, non-operative management (NOM) represents the standard approach even in high-severity injuries. However, knowledge, structural, and logistic limitations still reduce its wider diffusion. This study aims to identify such issues to promote the safe and effective management of these injuries.A survey was developed using the SurveyMonkey® software and spread nationally in Italy. The survey was structured into: (1) Knowledge of classification systems; (2) Availability to refer patients; (3) Patients monitoring and follow-up; (4) Center-related.The survey was filled in by 327 surgeons, with a completeness rate of 63%. Three responders out of four are used to manage trauma patients. Despite most responders knowing the existing classifications, their use is still limited in daily practice. If a patient needs to be centralized, the concern about possible clinical deterioration represent the main obstacle to achieving a NOM. The lack of protocols does not allow standardization of patient surveillance according to the degree of injury. The imaging follow-up is not standardized as well, varying between computed tomography, ultrasound, and contrast-enhanced ultrasound.The classification systems need to be spread to all the trauma-dedicated physicians, to speak a common language. A more rational centralization of patients should be promoted, ideally through agreements between peripheral and reference centers, both at regional and local level. Standardized protocols need to be shared nationally, as well as the clinical and imaging follow-up criteria should be adapted to the local features.

Identification of the ideal weight-based indocyanine green dose for fluorescent cholangiography.

BACKGROUND: Ideal visualization of fluorescent cholangiography during laparoscopic cholecystectomy is when maximum fluorescence into biliary ducts and absent signal into liver parenchyma, defined as "signal to background ratio" (SBR), is obtained. Such condition is mainly dependent by indocyanine green (ICG) dose and timing. The aim of this study was to identify the ideal ICG dose to obtain the best possible intraoperative visualization of the extra-hepatic biliary tree. METHODS: The first part of the study was used to define a range of small weight-based ICG dosages using the mathematical function bisection method. During the second part of the study, the midpoint dose of the identified range, was tested in 50 consecutive cholecystectomies using a laser-based fluorescence laparoscopic camera (SynergyID system by Arthrex, Naples, FL, USA). Timing administration was set at 1 h before surgery, since this is the most common situation in clinical practice. Fluorescence intensity of bile ducts and liver parenchyma were assessed both subjectively, by blinded operative surgeon, as well as objectively, using an image analysis software (Fiji plugin), before and after Calot's triangle dissection. RESULTS: Fourteen patients were included in the first part of the study and ICG dose between 0.01191406 and 0.0119873 mg/kg was identified. The second part confirmed previous results after testing the dosage equal to 0.0119 mg/kg (midpoint of the defined range) in 50 consecutive cholecystectomies. Cystic duct was identified in 66 and 100% of cases before and after dissection of Calot's triangle respectively. On the other hand, common bile duct was identified in 82 and 92% before and after dissection respectively. Subjective and objective SBRs confirmed the benefit of the identified ICG dose. CONCLUSION: ICG dose calculated by 0.0119 mg/kg administered one hour before surgery allows an ideal intraoperative visualization of the extra-hepatic biliary tree. REGISTRATION NUMBER: ISRCTN10190039.

Acute cholecystitis: Which flow-chart for the most appropriate management?

Acute cholecystitis (AC) is a very common disease in clinical practice. Laparoscopic cholecystectomy remains the gold standard treatment for AC, however due to aging population, the increased prevalence of multiple comorbidities and the extensive use of anticoagulants, surgical procedures may be too risky when dealing with patients in emergency settings. In these subsets of patients, a mini-invasive management may be an effective option, both as a definitive treatment or as bridge-to-surgery. In this paper, several non-operative treatments are described and their benefits and drawbacks are highlighted. Percutaneous gallbladder drainage (PT-GBD) is one of the most common and widespread techniques. It is easy to perform and has a good cost/benefit ratio. Endoscopic transpapillary gallbladder drainage (ETGBD) is a challenging procedure that is usually performed in high volume centers by expert endoscopists, and it has a specific indication for selected cases. EUS-guided drainage (EUS-GBD) is still not widely available, but it is an effective procedure that could have several advantages, especially in rate of reinterventions. All these treatment options should be considered together in a stepwise approach and addressed to patients after an accurate case-by-case evaluation in a multidisciplinary discussion. In this review, we provide a possible flowchart in order to optimize treatments, resource and provide to patients a tailored approach.

Three-Dimensional Transperineal Ultrasound Guiding Early Secondary Repair of Obstetric Anal Sphincter Injury in an Incontinent Patient without Suture Dehiscence.

We present the case of a 36-year-old primigravida who gave birth to a 3200 g baby by vacuum-assisted (Kiwi OmniCup™) operative vaginal delivery with mediolateral episiotomy. A "y"-shaped perineal tear with a grade IIIC obstetric anal sphincter injury (OASI) was diagnosed and repaired. Two days after delivery, in the absence of suture dehiscence, she started experiencing complete anal incontinence. A decision was made in association with a proctologic surgeon for an early secondary repair. Before surgery, a Three-dimensional transperineal ultrasound (TPUS) was performed. The exam revealed a major defect of the external anal sphincter at the 11 o'clock position. This allowed for the reopening of only a circumscribed area of the perineal suture and repair of the sphincters using the end-to-end technique. The symptoms regressed completely, and follow-up TPUS demonstrated the gradual wound healing process. Anal incontinence, secondary to obstetric anal sphincter injury (OASI), has a severe negative impact on women's quality of life. TPUS is an effective method to detect sphincter defects and monitor the healing process. This report investigates the feasibility of identifying the sphincter tear in an incontinent puerperal patient without suture dehiscence in order to target early secondary repair while minimizing its extent. TPUS has proven a safe and effective tool to guide early secondary repair of symptomatic OASI complications while minimizing the invasiveness of the procedure. Multidisciplinary management is crucial to ensure the adequate standard of care.

Endosonography-Guided Versus Percutaneous Gallbladder Drainage Versus Cholecystectomy in Fragile Patients with Acute Cholecystitis-A High-Volume Center Study.

Background and Objectives: Acute cholecystitis is a frequent cause of admission to the emergency department, especially in old and frail patients. Percutaneous drainage (PT-GBD) and endosonographic guided drainage (EUS-GBD) could be an alternative option for relieving symptoms or act as a definitive treatment instead of a laparoscopic or open cholecystectomy (LC, OC). The aim of the present study was to compare different treatment groups. Materials and Methods: This is a five-year monocentric retrospective study including patients ≥65 years old who underwent an urgent operative procedure. A descriptive analysis was conducted comparing all treatment groups. A propensity score was estimated based on the ACS score, incorporated into a predictive model, and tested by recursive partitioning analysis. Results: 163 patients were included: 106 underwent a cholecystectomy (81 laparoscopic (LC) and 25 Open (OC)), 33 a PT-GBD and 21 EUS-GBD. The sample was categorized into three prognostic groups according to the adverse event occurrence rate. All patients treated with EUS-GBD or LC resulted in the low risk group, and the adverse event rate (AE) was 10/96 (10.4%). The AE was 4/28 (14.2%) and 21/36 (58.3%) in the middle- and high-risk groups respectively (p < 0.001). These groups included all the patients who underwent an OC or a PT-GBD. The PT-GBD group had a lower clinical success rate (55.5%) and higher RR (16,6%) when compared with other groups. Conclusions: Surgery still represents the gold standard for AC treatment. Nevertheless, EUS-GBD is a good alternative to PT-GBD in terms of clinical success, RR and AEs in all kinds of patients.

Emergency General Surgery: Predicting Morbidity and Mortality in the Geriatric Population.

Introduction Numerous scoring systems have been created to predict the risk of morbidity and mortality in patients undergoing emergency general surgery (EGS). In this article, we compared the different scoring systems utilized at Humanitas Research Hospital and analyzed which one performed the best when assessing geriatric patients (>65 years of age). The scoring systems that were utilized were the APACHE II (Acute Physiology and Chronic Health Evaluation II), ASA (American Society of Anesthesiologists), ACS-NSQIP (American College of Surgeons-National Surgical Quality Improvement Program), Clinical Frailty Score, and the Clavien-Dindo classification as control. Materials and Methods We compiled a database consisting of all patients over the age of 65 who underwent EGS in a consecutive 24-month period between January 1, 2017 and December 31, 2018. We used the biostatistical program "Stata Version 15" to analyze our results. Results We found 213 patients who matched our inclusion criteria. Regarding death, we found that the ACS-NSQIP death calculator performed the best with an area under the curve of 0.9017 (odds ratio: 1.09; 95% confidence interval: 1.06-1.12). The APACHE II score had the lowest discriminator when predicting death. Considering short-term complications, the Clavien-Dindo classification scored highly, while both the APACHE II score and Clinical Frailty Score produced the lowest results. Conclusion The results obtained from our research showed that scoring systems and classifications produced different results depending on whether they were used to predict deaths or short-term complications among geriatric patients undergoing EGS.

Postoperative pain management in non-traumatic emergency general surgery: WSES-GAIS-SIAARTI-AAST guidelines.

BACKGROUND: Non-traumatic emergency general surgery involves a heterogeneous population that may present with several underlying diseases. Timeous emergency surgical treatment should be supplemented with high-quality perioperative care, ideally performed by multidisciplinary teams trained to identify and handle complex postoperative courses. Uncontrolled or poorly controlled acute postoperative pain may result in significant complications. While pain management after elective surgery has been standardized in perioperative pathways, the traditional perioperative treatment of patients undergoing emergency surgery is often a haphazard practice. The present recommended pain management guidelines are for pain management after non-traumatic emergency surgical intervention. It is meant to provide clinicians a list of indications to prescribe the optimal analgesics even in the absence of a multidisciplinary pain team. MATERIAL AND METHODS: An international expert panel discussed the different issues in subsequent rounds. Four international recognized scientific societies: World Society of Emergency Surgery (WSES), Global Alliance for Infection in Surgery (GAIS), Italian Society of Anesthesia, Analgesia Intensive Care (SIAARTI), and American Association for the Surgery of Trauma (AAST), endorsed the project and approved the final manuscript. CONCLUSION: Dealing with acute postoperative pain in the emergency abdominal surgery setting is complex, requires special attention, and should be multidisciplinary. Several tools are available, and their combination is mandatory whenever is possible. Analgesic approach to the various situations and conditions should be patient based and tailored according to procedure, pathology, age, response, and available expertise. A better understanding of the patho-mechanisms of postoperative pain for short- and long-term outcomes is necessary to improve prophylactic and treatment strategies.

Common bile duct stones management: A network meta-analysis.

BACKGROUND: Timely management is critical for treating symptomatic common bile duct (CBD) stones; however, a single optimal management strategy has yet to be defined in the acute care setting. Consequently, this systematic review and network meta-analysis, comparing one-stage (CBD exploration or intraoperative endoscopic retrograde cholangiopancreatography [ERCP] with simultaneous cholecystectomy) and two-stage (precholecystectomy or postcholecystectomy ERCP) procedures, was undertaken with the main outcomes of interest being postprocedural complications and hospital length of stay (LOS). METHODS: PubMed, SCOPUS, MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were methodically queried for articles from 2010 to 2021. The search terms were a combination of medical subject headings terms and the subsequent terms: gallstone; common bile duct (stone); choledocholithiasis; cholecystitis; endoscopic retrograde cholangiography/ERCP; common bile duct exploration; intraoperative, preoperative, perioperative, and postoperative endoscopic retrograde cholangiography; stone extraction; and one-stage and two-stage procedure. Studies that compared two procedures or more were included, whereas studies not recording complications (bile leak, hemorrhage, pancreatitis, perforation, intra-abdominal infections, and other infections) or LOS were excluded. A network meta-analysis was conducted to compare the four different approaches for managing CBD stones. RESULTS: A total of 16 studies (8,644 participants) addressing the LOS and 41 studies (19,756 participants) addressing postprocedural complications were included in the analysis. The one-stage approaches were associated with a decrease in LOS compared with the two-stage approaches. Common bile duct exploration demonstrated a lower overall risk of complications compared with preoperative ERCP, but there were no differences in the overall risk of complications in the remaining comparisons. However, differences in specific postprocedural complications were detected between the four different approaches managing CBD stones. CONCLUSION: This network meta-analysis suggests that both laparoscopic CBD exploration and intraoperative ERCP have equally good outcomes and provide a preferable single-anesthesia patient pathway with a shorter overall length of hospital stay compared with the two-stage approaches. LEVEL OF EVIDENCE: Systematic Review/Meta Analysis; Level III.

Open abdomen: is a dedicated emergency surgery team needed? A single center retrospective study on 141 consecutive patients.

BACKGROUND: Open Abdomen (OA) is widely used when facing a catastrophic abdomen. Still, no indication is validated by a strong and high quality of evidence. The study reports the 5 year experience of a dedicated emergency general surgery (EGS) team. METHODS: Retrospective observational cohort study. Patients undergoing OA management from 2/01/2015 to 19/07/2020 for trauma, non-traumatic emergencies or rescue surgery. RESULTS: One hundred and forty-one patients. Age 66.9 ± 15.1. Male 58.2%.9.3% OA for trauma, 64.5% for non-traumatic emergencies and 26.2% for rescue surgery. 40.4% performed by the EGS team 52.4% indication for surgery was a severe intra-abdominal infection. TAC device: commercial negative pressure wound therapy (NPWT) (83%), Sandwich VAC (12%), commercial NPWT with polypropylene mesh (5%) for pregressive fascial traction. Enteroatmospheric fistula (EAF) in 3 patients. OA duration 5.3 days (1-25). A 1.8 revision surgeries (0-12) required for definitive closure; ICU stay 9.9 days (0-78). 30-day mortality 23.5%. Overall and 1-year mortality were 47.5% and 43.3%. Overall survival 9.9 months. An increased one-year mortality rate was found in the >65 group (P = 0.01). CONCLUSIONS: We reported a wide use of OA in septic abdomen (90% of cases). We had a low rate of EAF, short ICU stay and OA duration. These results are related to the fact that patients were treated by a dedicated EGS team, suggesting that OA management should be cared for as much as possible by trained and experienced surgeons. Prospective studies with more accurate patient selection are needed to prove our conclusions.

The effect of COVID-19 epidemic on vital signs in hospitalized patients: a pre-post heat-map study from a large teaching hospital.

The Lombardy SARS-CoV-2 outbreak in February 2020 represented the beginning of COVID-19 epidemic in Italy. Hospitals were flooded by thousands of patients with bilateral pneumonia and severe respiratory, and vital sign derangements compared to the standard hospital population. We propose a new visual analysis technique using heat maps to describe the impact of COVID-19 epidemic on vital sign anomalies in hospitalized patients. We conducted an electronic health record study, including all confirmed COVID-19 patients hospitalized from February 21st, 2020 to April 21st, 2020 as cases, and all non-COVID-19 patients hospitalized in the same wards from January 1st, 2018 to December 31st, 2018. All data on temperature, peripheral oxygen saturation, respiratory rate, arterial blood pressure, and heart rate were retrieved. Derangement of vital signs was defined according to predefined thresholds. 470 COVID-19 patients and 9241 controls were included. Cases were older than controls, with a median age of 79 vs 76 years in non survivors (p = < 0.002). Gender was not associated with mortality. Overall mortality in COVID-19 hospitalized patients was 18%, ranging from 1.4% in patients below 65 years to about 30% in patients over 65 years. Heat maps analysis demonstrated that COVID-19 patients had an increased frequency in episodes of compromised respiratory rate, acute desaturation, and fever. COVID-19 epidemic profoundly affected the incidence of severe derangements in vital signs in a large academic hospital. We validated heat maps as a method to analyze the clinical stability of hospitalized patients. This method may help to improve resource allocation according to patient characteristics.

Erratum: Addendum: Emergency General Surgery: Predicting Morbidity and Mortality in the Geriatric Population.

[This corrects the article DOI: 10.1055/s-0042-1756461.].

Management of patients with cervical spine trauma in the emergency department: a systematic critical appraisal of guidelines with a view to developing standardized strategies for clinical practice.

Several guidelines on the evaluation of patients with suspected cervical spine trauma in the Emergency Department (ED) exist. High heterogeneity between different guidelines has been reported. Aim of this study was to find areas of agreement and disagreement between guidelines, to identify topics in which further research is needed and to provide an evidence-based cervical spine trauma algorithm for ED physicians. The three most relevant guidelines published on cervical spine trauma in the last 10 years were selected screening websites of the main scientific societies and through the comparison of a normalized Google Scholar and SCOPUS citation index. We compared the selected guidelines through seven a-priori defined questions. In case of disagreement between the guidelines or if the quality of evidence appeared low, evidence from published systematic reviews on the topic was added to build an evidence-based algorithm for approach to spinal trauma in the ED. The three selected guidelines were: NICE 2016, Eastern Association for the Surgery of Trauma 2009 and American Association of Neurological Surgeons and Congress of Neurological Surgeons 2013. We found complete agreement on one question, partial agreement for one questions, no agreement for two questions, while agreement was not assessable for 3 questions. The agreement between different guidelines and the evidence on which recommendations are based is low. An attempt to build an evidence-based algorithm has been made. More studies are needed on many topics.