Physical activity decreases in patients on the liver transplant waiting list and influences postoperative outcome-a prospective cohort study.

Background: Physical deconditioning affects patients suffering from end-stage liver disease (ESLD). Liver transplantation (LT) is the only curative option for ESLD. Growing evidence suggests that pre-habilitation is beneficial in reducing post-surgical morbidity and mortality. We investigated physical activity (PA) in patients awaiting LT in a country with long waiting times. Methods: Prospective, single center, longitudinal study in Bern, Switzerland between June 2019 and February 2020 (halted due to SARS-CoV-2 pandemic), with follow-up data up to six months post-transplant. Patients were instructed to use a wrist tracker (FitBit) to monitor PA, which was assessed using mixed-effects generalized linear models. The study was approved by the local ethics committee (BASEC ID 2019-00606). Results: Thirty-five patients were included [71% male, median 59 years, body mass index (BMI) 28 kg/m2, lab Model End-Stage Liver Disease (MELD) 11], 17 (49%) pre-frail and 5 (14%) frail according to the Liver Frailty Index (LFI). Twenty-eight patients underwent transplantation with 0 ninety-day mortality and 15 (53.6%) composite adverse clinical outcome. Median daily steps were 4,661 [interquartile range (IQR), 1,685-8,609] and weekly moderate PA (MPA) was 41 min (IQR, 0-127 min). Longitudinal analysis showed that female patients and patients on nutritional support had an increase in MPA between weeks 20 and 40. A significant decrease was seen in MPA after week 40, whilst no significant association was seen with age, Child-Pugh Score, LFI or quality of life at time of inclusion. MPA was significantly associated with the occurrence of the composite clinical endpoint after week 30 of waiting time (odds ratio 0.882, P=0.026). World Health Organization (WHO)-recommended MPA was significantly associated with less adverse composite clinical outcomes (P<0.001). Conclusions: In patients listed for LT, MPA decreased over time, showing a significant association with adverse outcome, specifically after week 30 on the waiting list. Our data support the implementation of routine pre-habilitation in patients awaiting LT.

Infectious Disease in the Workplace: Quantifying Uncertainty in Transmission.

Understanding disease transmission in the workplace is essential for protecting workers. To model disease outbreaks, the small populations in many workplaces require that stochastic effects are considered, which results in higher uncertainty. The aim of this study was to quantify and interpret the uncertainty inherent in such circumstances. We assessed how uncertainty of an outbreak in workplaces depends on i) the infection dynamics in the community, ii) the workforce size, iii) spatial structure in the workplace, iv) heterogeneity in susceptibility of workers, and v) heterogeneity in infectiousness of workers. To address these questions, we developed a multiscale model: A deterministic model to predict community transmission, and a stochastic model to predict workplace transmission. We extended this basic workplace model to allow for spatial structure, and heterogeneity in susceptibility and infectiousness in workers. We found a non-monotonic relationship between the workplace transmission rate and the coefficient of variation (CV), which we use as a measure of uncertainty. Increasing community transmission, workforce size and heterogeneity in susceptibility decreased the CV. Conversely, increasing the level of spatial structure and heterogeneity in infectiousness increased the CV. However, when the model predicts bimodal distributions, for example when community transmission is low and workplace transmission is high, the CV fails to capture this uncertainty. Overall, our work informs modellers and policy makers on how model complexity impacts outbreak uncertainty. In particular: workforce size, community and workplace transmission, spatial structure and individual heterogeneity contribute in a specific and individual manner to the predicted workplace outbreak size distribution.

The trajectory of anti-recEm18 antibody levels determines follow-up after curative resection of hepatic alveolar echinococcosis.

INTRODUCTION: Recurrence after curative resection of hepatic alveolar echinococcosis remains a clinical challenge. The current study tested if assessment of anti-recEm18 allows for postsurgical patient surveillance. METHODS: A retrospective study with patients undergoing liver resection for alveolar echinococcosis (n = 88) at the University Hospital Bern from 2002 to 2020 and at the University Hospital and Medical Center Ulm from 2011 to 2017 was performed. Analysis was directed to determine a potential association of pre- and postoperative values of anti-recEm18 with clinical outcomes. RESULTS: Anti-recEm18 had a linear correlation to the maximum lesion diameter (R2 = 0.558). Three trajectories of anti-recEm18 were identified based on a threshold of 10 AU/ml: "Em18-low" (n = 31), "responders" (n = 53) and "residual disease" (n = 4). The decline of anti-recEm18 in "responders" reached a plateau after 10.9 months at which levels decreased by 90%. The only patient with recurrence in the entire population was also the only patient with a secondary increase of anti-recEm18. CONCLUSION: In patients with preoperative elevated values, anti-recEm18 confirms curative surgery at 12 months follow-up and allows for long-term surveillance.

Intestinal dysbiosis as an intraoperative predictor of septic complications: evidence from human surgical cohorts and preclinical models of peritoneal sepsis.

Major surgery exposes the intestinal microbiota to inflammatory and antibiotic stressors, which alter the microbiota composition of the intestinal lumen and fecal contents. However, it is not sufficiently understood, if such dysbiosis develops already during surgery and if alterations in microbiota may be the cause of surgical complications. End-of-surgery composition of the microbiota in the rectum was assessed in 41 patients undergoing either rectal or duodenopancreatic resection and was compared to baseline before surgery using 16S-rRNA sequencing. A subset of patients developed severe dysbiosis at the end of surgery, which was characterized by an overgrowth of the Proteobacteria phylum that includes the facultative pathogen E. coli. To test if dysbiosis impacts on surgical outcomes, dysbiosis was modeled in mice by a single oral administration of vancomycin prior to cecal ligation and puncture. Dysbiosis was associated with impaired post-surgical survival, dysregulation of the host's immune response, elevated bacterial virulence and reduced bacterial metabolism of carbon sources. In conclusion, dysbiosis can be detected already at the end of surgery in a fraction of patients undergoing major surgery. Modelling surgery-associated dysbiosis in mice using single-shot administration of vancomycin induced dysbiosis and resulted in elevated mortality.

An APRI+ALBI Based Multivariable Model as Preoperative Predictor for Posthepatectomy Liver Failure.

OBJECTIVE AND BACKGROUND: Clinically significant posthepatectomy liver failure (PHLF B+C) remains the main cause of mortality after major hepatic resection. This study aimed to establish an APRI+ALBI, aspartate aminotransferase to platelet ratio (APRI) combined with albumin-bilirubin grade (ALBI), based multivariable model (MVM) to predict PHLF and compare its performance to indocyanine green clearance (ICG-R15 or ICG-PDR) and albumin-ICG evaluation (ALICE). METHODS: 12,056 patients from the National Surgical Quality Improvement Program (NSQIP) database were used to generate a MVM to predict PHLF B+C. The model was determined using stepwise backwards elimination. Performance of the model was tested using receiver operating characteristic curve analysis and validated in an international cohort of 2,525 patients. In 620 patients, the APRI+ALBI MVM, trained in the NSQIP cohort, was compared with MVM's based on other liver function tests (ICG clearance, ALICE) by comparing the areas under the curve (AUC). RESULTS: A MVM including APRI+ALBI, age, sex, tumor type and extent of resection was found to predict PHLF B+C with an AUC of 0.77, with comparable performance in the validation cohort (AUC 0.74). In direct comparison with other MVM's based on more expensive and time-consuming liver function tests (ICG clearance, ALICE), the APRI+ALBI MVM demonstrated equal predictive potential for PHLF B+C. A smartphone application for calculation of the APRI+ALBI MVM was designed. CONCLUSION: Risk assessment via the APRI+ALBI MVM for PHLF B+C increases preoperative predictive accuracy and represents an universally available and cost-effective risk assessment prior to hepatectomy, facilitated by a freely available smartphone app.

Alone Together: Is Strain Experienced Concurrently by Members of Operating Room Teams?: An Event-based Study.

Objective: To identify which strain episodes are concurrently reported by several team members; to identify triggers of strain experienced by operating room (OR) team members during the intraoperative phase. Summary: OR teams are confronted with many sources of strain. However, most studies investigate strain on a general, rather than an event-based level, which does not allow to determine if strain episodes are experienced concurrently by different team members. Methods: We conducted an event-based, observational study, at an academic medical center in North America and included 113 operations performed in 5 surgical departments (general, vascular, pediatric, gynecology, and trauma/acute care). Strain episodes were assessed with a guided-recall method. Immediately after operations, participants mentally recalled the operation, described the strain episodes experienced and their content. Results: Based on 731 guided recalls, 461 strain episodes were reported; these refer to 312 unique strain episodes. Overall, 75% of strain episodes were experienced by a single team member only. Among different categories of unique strain episodes, those triggered by task complexity, issues with material, or others' behaviors were typically experienced by 1 team member only. However, acute patient issues (n = 167) and observations of others' strain (n = 12) (respectively, 58.5%; P < 0.001 and 83.3%; P < 0.001) were often experienced by 2 or more team members. Conclusions and relevance: OR team members are likely to experience strain alone, unless patient safety is at stake. This may jeopardize the building of a shared understanding among OR team members.

Technical skill assessment in minimally invasive surgery using artificial intelligence: a systematic review.

BACKGROUND: Technical skill assessment in surgery relies on expert opinion. Therefore, it is time-consuming, costly, and often lacks objectivity. Analysis of intraoperative data by artificial intelligence (AI) has the potential for automated technical skill assessment. The aim of this systematic review was to analyze the performance, external validity, and generalizability of AI models for technical skill assessment in minimally invasive surgery. METHODS: A systematic search of Medline, Embase, Web of Science, and IEEE Xplore was performed to identify original articles reporting the use of AI in the assessment of technical skill in minimally invasive surgery. Risk of bias (RoB) and quality of the included studies were analyzed according to Quality Assessment of Diagnostic Accuracy Studies criteria and the modified Joanna Briggs Institute checklists, respectively. Findings were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS: In total, 1958 articles were identified, 50 articles met eligibility criteria and were analyzed. Motion data extracted from surgical videos (n = 25) or kinematic data from robotic systems or sensors (n = 22) were the most frequent input data for AI. Most studies used deep learning (n = 34) and predicted technical skills using an ordinal assessment scale (n = 36) with good accuracies in simulated settings. However, all proposed models were in development stage, only 4 studies were externally validated and 8 showed a low RoB. CONCLUSION: AI showed good performance in technical skill assessment in minimally invasive surgery. However, models often lacked external validity and generalizability. Therefore, models should be benchmarked using predefined performance metrics and tested in clinical implementation studies.

No signs of check-list fatigue - introducing the StOP? intra-operative briefing enhances the quality of an established pre-operative briefing in a pre-post intervention study.

Background: The team timeout (TTO) is a safety checklist to be performed by the surgical team prior to incision. Exchange of critical information is, however, important not only before but also during an operation and members of surgical teams frequently feel insufficiently informed by the operating surgeon about the ongoing procedure. To improve the exchange of critical information during surgery, the StOP?-protocol was developed: At appropriate moments during the procedure, the leading surgeon briefly interrupts the operation and informs the team about the current Status (St) and next steps/objectives (O) of the operation, as well as possible Problems (P), and encourages questions of other team members (?). The StOP?-protocol draws attention to the team. Anticipating the occurrence of StOP?-protocols may support awareness of team processes and quality issues from the beginning and thus support other interventions such as the TTO; however, it also may signal an additional demand and contribute to a phenomenon akin to "checklist fatigue." We investigated if, and how, the introduction of the StOP?-protocol influenced TTO quality. Methods: This was a prospective intervention study employing a pre-post design. In the visceral surgical departments of two university hospitals and one urban hospital the quality of 356 timeouts (out of 371 included operation) was assessed by external observers before (154) and after (202) the introduction of the StOP?-briefing. Timeout quality was rated in terms of timeout completeness (number of checklist items mentioned) and timeout quality (engagement, pace, social atmosphere, noise). Results: As compared to the baseline, after the implementation of the StOP?-protocol, observed timeouts had higher completeness ratings (F = 8.69, p = 0.003) and were rated by observers as higher in engagement (F = 13.48, p < 0.001), less rushed (F = 14.85, p < 0.001), in a better social atmosphere (F = 5.83, p < 0.016) and less noisy (F = 5.35, p < 0.022). Conclusion: Aspects of TTO are affected by the anticipation of StOP?-protocols. However, rather than harming the timeout goals by inducing "checklist fatigue," it increases completeness and quality of the team timeout.

Predictors for surgical site infection in patients undergoing therapeutic or prophylactic intra-abdominal onlay mesh (IPOM) implantation in clean and contaminated surgical fields.

BACKGROUND: Prophylactic intra-abdominal onlay mesh (IPOM) implantation has been shown to reduce the rate of fascial dehiscence and incisional hernia. However, surgical site infection (SSI) in presence of an IPOM remains a concern. The aim of this study was to assess predictors for SSI following IPOM placement in hernia and non-hernia abdominal surgery in clean and contaminated surgical fields. METHODS: Observational study including patients undergoing IPOM placement at a Swiss tertiary care hospital 2007-2016. IPOM implantation was performed in hernia and non-hernia elective and emergency abdominal surgery, including contaminated and infected surgical fields. The incidence of SSI was prospectively assessed by Swissnoso according to CDC criteria. The effect of disease- and procedure-related factors on SSI was assessed in multivariable regression analysis, adjusting for patient-related factors. RESULTS: A total of 1072 IPOM implantations were performed. Laparoscopy was performed in 415 patients (38.7%), laparotomy in 657 patients (61.3%). SSI occurred in 172 patients (16.0%). Superficial, deep, and organ space SSI were found in 77 (7.2%), 26 (2.4%), and 69 (6.4%) patients, respectively. Multivariable analysis revealed emergency hospitalization (OR 1.787, p = 0.006), previous laparotomy (1.745, p = 0.029), duration of operation (OR 1.193, p < 0.001), laparotomy (OR 6.167, p < 0.001), bariatric (OR 4.641, p < 0.001), colorectal (OR 1.941, p = 0.001), and emergency (OR 2.510, p < 0.001) surgery, wound class ≥ 3 (OR 3.878, p < 0.001), and non-polypropylene mesh (OR 1.818, p = 0.003) as independent predictors for SSI. Hernia surgery was independently associated with a lower risk for SSI (OR 0.165, p < 0.001). CONCLUSION: This study revealed emergency hospitalization, previous laparotomy, duration of operation, laparotomy, as well as bariatric, colorectal, and emergency surgery, abdominal contamination or infection, and usage of non-polypropylene mesh as independent predictors for SSI. In contrast, hernia surgery was associated with a lower risk for SSI. The knowledge of these predictors will help to balance benefits of IPOM implantation against the risk for SSI.

ILC3s restrict the dissemination of intestinal bacteria to safeguard liver regeneration after surgery.

It is generally believed that environmental or cutaneous bacteria are the main origin of surgical infections. Therefore, measures to prevent postoperative infections focus on optimizing hygiene and improving asepsis and antisepsis. In a large cohort of patients with infections following major surgery, we identified that the causative bacteria are mainly of intestinal origin. Postoperative infections of intestinal origin were also found in mice undergoing partial hepatectomy. CCR6+ group 3 innate lymphoid cells (ILC3s) limited systemic bacterial spread. Such bulwark function against host invasion required the production of interleukin-22 (IL-22), which controlled the expression of antimicrobial peptides in hepatocytes, thereby limiting bacterial spread. Using genetic loss-of-function experiments and punctual depletion of ILCs, we demonstrate that the failure to restrict intestinal commensals by ILC3s results in impaired liver regeneration. Our data emphasize the importance of endogenous intestinal bacteria as a source for postoperative infection and indicate ILC3s as potential new targets.

Plasticity of the adult human small intestinal stoma microbiota.

The human distal small intestine (ileum) has a distinct microbiota, but human studies investigating its composition and function have been limited by the inaccessibility of the ileum without purging and/or deep intubation. We investigated inherent instability, temporal dynamics, and the contribution of fed and fasted states using stoma samples from cured colorectal cancer patients as a non-invasive access route to the otherwise inaccessible small and large intestines. Sequential sampling of the ileum before and after stoma formation indicated that ileostoma microbiotas represented that of the intact small intestine. Ileal and colonic stoma microbiotas were confirmed as distinct, and two types of instability in ileal host-microbial relationships were observed: inter-digestive purging followed by the rapid postprandial blooming of bacterial biomass and sub-strain appearance and disappearance within individual taxa after feeding. In contrast to the relative stability of colonic microbiota, the human small intestinal microbiota biomass and its sub-strain composition can be highly dynamic.

Risk factors for chronic postsurgical pain in visceral surgery: a matched case-control analysis.

PURPOSE: Chronic postsurgical pain (CPSP) after abdominal visceral surgery is an underestimated long-term complication with relevant impact on health-related quality of life and socioeconomic costs. Early identification of affected patients is important. We aim to identify the incidence and risk factors for CPSP in this patient population. METHODS: Retrospective case-control matched analysis including all patients diagnosed with CPSP after visceral surgery in our institution between 2016 and 2019. One-to-two case-control matching was based on operation category (HPB, upper-GI, colorectal, transplantation, bariatric, hernia and others) and date of surgery. Potential risk factors for CPSP were identified using conditional multivariate logistic regression. RESULTS: Among a cohort of 3730 patients, 176 (4.7%) were diagnosed with CPSP during the study period and matched to a sample of 352 control patients. Independent risk factors for CPSP were age under 55 years (OR 2.64, CI 1.51-4.61), preexisting chronic pain of any origin (OR 3.42, CI 1.75-6.67), previous abdominal surgery (OR 1.99, CI 1.11-3.57), acute postoperative pain (OR 1.29, CI 1.16-1.44), postoperative use of non-steroidal anti-inflammatory drugs (OR 3.73, OR 1.61-8.65), opioid use on discharge (OR 3.78, CI 2.10-6.80) and length of stay over 3 days (OR 2.60, CI 1.22-5.53). Preoperative Pregabalin intake was protective (OR 0.02, CI 0.002-0.21). CONCLUSION: The incidence of CPSP is high and associated with specific risk factors, some of them modifiable. Special attention should be given to sufficient treatment of preexisting chronic pain and acute postoperative pain.

Empyema after image-guided percutaneous intercostal drainage of subdiaphragmatic collection: a case series.

Background: Treatment of subdiaphragmatic collection by intercostal image-guided drain placement is associated with a risk of pleural complications including potentially life-threatening pleural empyema. Descriptions of patient characteristics and clinical course of postinterventional pleural empyema are lacking. We aim to present characteristics, clinical course and outcomes of patients with empyema after intercostal approach of drain placement. Methods: Data was collected as a retrospective single center case series and included adult patients with decortication for treatment of pleural empyema after image-guided percutaneous intercostal drainage of a subdiaphragmatic collection between 01.01.2009 and 31.01.2021. Results: We identified ten patients, nine male and one female, all suffering from subdiaphragmatic collection treated with intercostal drain. All patients developed pleural empyema after drain placement and received surgical decortication. Similarities between patients were drain placement under computed tomography (CT)-guidance (eight of ten patients), lateral position of the drain (seven of ten patients), drain insertion in the eighth intercostal space (ICS) (six of ten patients) and existing comorbidities as malnutrition (six of ten patients), diabetes (four of ten patients) and cancer (three of ten patients). The majority of patients had a prolonged length of hospital stay (LOS) with an average duration of 40 days. Nearly half of the patients needed intensive care unit (ICU) treatment and one patient died postoperatively from respiratory exhaustion. Conclusions: In this series, empyema after intercostal drainage was associated with prolonged LOS and was potentially life-threatening. The most commonly shared features in our cohort were the high prevalence of comorbidities, drain insertion above ninth ICS as well as lateral position of the drain. These factors should be addressed in prospective studies to evaluate potential correlation with postinterventional empyema. For optimal management of patients with subdiaphragmatic collection treated by intercostal drainage, awareness of potential associated complications is crucial.

StOP? II trial: cluster randomized clinical trial to test the implementation of a toolbox for structured communication in the operating room-study protocol.

BACKGROUND: Surgical care, which is performed by intensely interacting multidisciplinary teams of surgeons, anesthetists, and nurses, remains associated with significant morbidity and mortality. Intraoperative communication has been shown to be associated with surgical outcomes, but tools ensuring efficient intraoperative communication are lacking. In a previous study, we developed the StOP?-protocol that fosters structured intraoperative communication. Before the critical phases of the operation, the responsible surgeon initiates and leads one or several StOP?s. During a StOP?, the surgeon informs about the progress of the operation (status), next steps and proximal goals (objectives), and possible problems (problems) and encourages all team members to voice their observations and ask questions (?). In a before-after study performed mainly in visceral surgery, we found effects of the StOP?-protocol on mortality, length of hospital stay, and reoperation. We intend to assess the impact of the StOP?-protocol in a cluster randomized trial, in a wider variety of surgical specialties (i.e., general, visceral, thoracic, vascular surgery, surgical urology, and gynecology). The primary hypothesis is that the consistent use of the StOP?-protocol by the main surgeon reduces patient mortality within 30 days after the operation. The secondary hypothesis is that the consistent use of the StOP?-protocol by the main surgeon reduces unplanned reoperations, length of hospital stay, and unplanned hospital readmissions. METHODS: This study is designed as a multicenter, cluster-randomized parallel-group trial. Board-certified surgeons of participating clinical departments will be randomized 1:1 to the StOP? intervention group or to the standard of care (control) group. The intervention group will undergo a training to use the StOP?-protocol and receive regular feedback on their compliance with the protocol. The surgeons in the control group will communicate as usual during their operations. The unit of observation will be operations performed by cluster surgeons. Consecutive patients will be enrolled over 4 months per cluster. A total of 400 surgeons will be recruited, and we expect to collect patient outcome data for 14,000 surgical procedures. DISCUSSION: The StOP?-protocol was designed as a tool to structure communication during surgical procedures. Testing its effects on patient outcomes will contribute to implementing evidenced-based interventions to reduce surgical complications. TRIAL REGISTRATION: ClinicalTrials.gov NCT05356962. Registered on May 2, 2022.

No impact of sex on surgical site infections in abdominal surgery: a multi-center study.

OBJECTIVE: Male sex is controversially discussed as a risk factor for surgical site infections (SSI). The aim of the present study was to evaluate the impact of sex on SSI in abdominal surgery under elimination of relevant confounders. METHODS: Clinicopathological data of 6603 patients undergoing abdominal surgery from a multi-center prospective database of four Swiss hospitals including patients between 2015 and 2018 were assessed. Patients were stratified according to postoperative SSI and risk factors for SSI were identified using univariate and multivariate analysis. RESULTS: In 649 of 6603 patients, SSI was reported (9.8%). SSI was significantly associated with reoperation (22.7% vs. 3.4%, p < 0.001), increased mortality rate (4.6% vs. 0.9%, p < 0.001), and increased rate of length of hospital stay > 75th percentile (57.0% vs. 17.9%, p < 0.001). In univariate analysis, male sex was a significant risk factor for SSI (p = 0.01). In multivariate analysis including multiple confounders' such as comorbidities and perioperative factors, there was no association between male sex and risk of SSI (odds ratio (OR) 1.1 [CI 0.8-1.4]). Independent risk factors for SSI in multivariate analysis were BMI ≥ 30 kg/m2 (OR 1.8 [CI 1.3-2.3]), duration of surgery > 75th percentile (OR 2.3 [1.8-2.9]), high contamination level (OR 1.3 [1.0-1.6]), laparotomy (OR 1.3 [1.0-1.7]), previous laparotomy (OR 1.4 [1.1-1.7]), blood transfusion (OR 1.7 [1.2-2.4]), cancer (OR 1.3 [1.0-1.8] and malnutrition (OR 2.5 [1.8-3.4]). CONCLUSION: Under elimination of relevant confounders, there is no significant correlation between sex and risk of SSI after abdominal surgery.

Laparoscopic resection of hepatic alveolar echinococcosis: A single-center experience.

INTRODUCTION: Alveolar echinococcosis (AE) remains a very rare disease requiring complete radical resection for curative treatment. While open approaches are common, safety and efficacy of laparoscopic resections remain unknown. METHODS: This is a single-center, retrospective cohort study with patients undergoing liver resection for hepatic AE at the Department of Visceral Surgery and Medicine, Bern University Hospital from December 2002 to December 2020. Postoperative outcomes of patients following laparoscopic hepatectomy (LH) for hepatic AE were compared with those of patients undergoing open hepatectomy (OH). RESULTS: A total of 93 patients underwent liver resection for hepatic AE. Laparoscopic hepatectomy was performed in 23 patients and open hepatectomy in 70 patients. While there were no significant differences in terms of gender, age and diagnostic tools, the majority of patients of the LH cohort were PNM stage 1 (78%) in contrast to only 39% in the OH cohort (p = 0.002). Patients undergoing laparoscopic hepatectomy were treated by minor liver resections in 91% and in 9% by major liver resections in comparison to the open hepatectomy cohort with 61% major liver resections and 39% minor resections. Laparoscopic hepatectomy was associated with shorter mean operation time (127 minutes vs. 242 minutes, p <0.001), lower major complication rate (0% vs. 11%, p = 0.322) and shorter mean length of hospital stay (4 days vs. 13 days, p <0.001). Patients with LH had a distinct, but not significant lower recurrence rate (0% vs. 4%, p = 0.210) during a mean follow-up of 55 months compared with a follow-up of 76 months in the OH cohort. After subgroup analysis of PNM stage 1 patients, similar results are seen with persistent shorter mean operation time (120 minutes vs. 223 minutes, p <0.001), lower major complication rate (0% vs. 8%, p = 0.759) and shorter length of hospital stay (4 days vs. 12 days, p <0.001). CONCLUSION: Laparoscopy appears as a feasible and safe approach for patients with PNM stage 1 alveolar echinococcosis without impact on early disease recurrence.

Hepatic blood flow regulation but not oxygen extraction capability is impaired in prolonged experimental abdominal sepsis.

Impaired oxygen utilization has been proposed to play a significant role in sepsis-induced liver dysfunction, but its magnitude and temporal course during prolonged resuscitation is controversial. The aim of this study is to evaluate the capability of the liver to increase oxygen extraction in sepsis during repeated acute portal vein blood flow reduction. Twenty anesthetized and mechanically ventilated pigs with hepatic hemodynamic monitoring were randomized to fecal peritonitis or controls (n = 10, each). After 8-h untreated sepsis, the animals were resuscitated for three days. The ability to increase hepatic O2 extraction was evaluated by repeated, acute decreases in hepatic oxygen delivery (Do2) via reduction of portal flow. Blood samples for liver function and liver biopsies were obtained repeatedly. Although liver function tests, ATP content, and Do2 remained unaltered, there were signs of liver injury in blood samples and overt liver cell necrosis in biopsies. With acute portal vein occlusion, hepatic Do2 decreased more in septic animals compared with controls [max. decrease: 1.66 ± 0.68 mL/min/kg in sepsis vs. 1.19 ± 0.42 mL/min/kg in controls; portal venous flow (Qpv) reduction-sepsis interaction: P = 0.028]. Hepatic arterial buffer response (HABR) was impaired but recovered after 3-day resuscitation, whereas hepatic oxygen extraction increased similarly during the procedures in both groups (max. increase: 0.27 ± 0.13 in sepsis vs. 0.18 ± 0.09 in controls; all P > 0.05). Our data indicate maintained capacity of the liver to acutely increase O2 extraction, whereas blood flow regulation is transiently impaired with the potential to contribute to liver injury in sepsis.NEW & NOTEWORTHY The capacity to acutely increase hepatic O2 extraction with portal flow reduction is maintained in sepsis with accompanying liver injury, but hepatic blood flow regulation is impaired.

Primary Infection by E. multilocularis Induces Distinct Patterns of Cross Talk between Hepatic Natural Killer T Cells and Regulatory T Cells in Mice.

The larval stage of the helminthic cestode Echinococcus multilocularis can inflict tumor-like hepatic lesions that cause the parasitic disease alveolar echinococcosis in humans, with high mortality in untreated patients. Opportunistic properties of the disease have been established based on the increased incidence in immunocompromised patients and mouse models, indicating that an appropriate adaptive immune response is required for the control of the disease. However, cellular interactions and the kinetics of the local hepatic immune responses during the different stages of infection with E. multilocularis remain unknown. In a mouse model of oral infection that mimics the normal infection route in human patients, the networks of the hepatic immune response were assessed using single-cell RNA sequencing (scRNA-seq) of isolated hepatic CD3+ T cells at different infection stages. We observed an early and sustained significant increase in natural killer T (NKT) cells and regulatory T cells (Tregs). Early tumor necrosis factor (TNF)- and integrin-dependent interactions between these two cell types promote the formation of hepatic lesions. At late time points, downregulation of programmed cell death protein 1 (PD-1) and ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1)-dependent signaling suppress the resolution of parasite-induced pathology. The obtained data provide fresh insight into the adaptive immune responses and local regulatory pathways at different infection stages of E. multilocularis in mice.