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Unhealthy dietary habits can contribute to the development of colorectal cancer (CRC). Such habits may also be associated with post-treatment symptoms experienced by CRC survivors. Therefore, we aimed to assess longitudinal associations of post-treatment unhealthy dietary habits, i.e. intake of ultra-processed foods (UPF), red and processed meat, alcohol and sugar-sweetened drinks, with health-related quality of life (HRQoL), fatigue and chemotherapy-induced peripheral neuropathy (CIPN) in CRC survivors from 6 weeks up to 24 months post-treatment. In a prospective cohort among stage I-III CRC survivors (n 396), five repeated home visits from diagnosis up to 24 months post-treatment were executed. Dietary intake was measured by 7-d dietary records to quantify consumption of UPF, red and processed meat, alcohol and sugar-sweetened drinks. HRQoL, fatigue and CIPN were measured by validated questionnaires. We applied confounder-adjusted linear mixed models to analyse longitudinal associations from 6 weeks until 24 months post-treatment. We applied a post hoc time-lag analysis for alcohol to explore the directionality. Results showed that higher post-treatment intake of UPF and sugar-sweetened drinks was longitudinally associated with worsened HRQoL and more fatigue, while higher intake of UPF and processed meat was associated with increased CIPN symptoms. In contrast, post-treatment increases in alcohol intake were longitudinally associated with better HRQoL and less fatigue; however, time-lag analysis attenuated these associations. In conclusion, unhealthy dietary habits are longitudinally associated with lower HRQoL and more symptoms, except for alcohol. Results from time-lag analysis suggest no biological effect of alcohol; hence, the longitudinal association for alcohol should be interpreted with caution.

Item does not contain fulltext OBJECTIVE: To establish an evidence-based cutoff and predictors for early recurrence in patients with resected locally advanced pancreatic cancer (LAPC). BACKGROUND: It is unclear how many and which patients develop early recurrence after LAPC resection. Surgery in these patients is probably of little benefit. METHODS: We analyzed all consecutive patients undergoing resection of LAPC after induction chemotherapy who were included in prospective databases in The Netherlands (2015-2019) and the Johns Hopkins Hospital (2016-2018). The optimal definition for "early recurrence" was determined by the post-recurrence survival (PRS). Patients were compared for overall survival (OS). Predictors for early recurrence were evaluated using logistic regression analysis. RESULTS: Overall, 168 patients were included. After a median follow-up of 28 months, recurrence was observed in 118 patients (70.2%). The optimal cutoff for recurrence-free survival to differentiate between early (n=52) and late recurrence (n=66) was 6 months ( P

BackgroundPatients often need admission at an Intensive Care Unit (ICU), immediately after complex abdominal wall reconstruction (CAWR). Lack of ICU resources requires adequate patient selection for a planned postoperative ICU admission. Risk stratification tools like Fischer score and Hernia Patient Wound (HPW) classification may improve patient selection. This study evaluates the decision-making process in a multidisciplinary team (MDT) on justified ICU admissions for patients after CAWR.MethodsA pre-Covid-19 pandemic cohort of patients, discussed in a MDT and subsequently underwent CAWR between 2016 and 2019, was analyzed. A justified ICU admission was defined by any intervention within the first 24 h postoperatively, considered not suitable for a nursing ward. The Fischer score predicts postoperative respiratory failure by eight parameters and a high score (> 2) warrants ICU admission. The HPW classification ranks complexity of hernia (size), patient (comorbidities) and wound (infected surgical field) in four stages, with increasing risk for postoperative complications. Stages II-IV point to ICU admission. Accuracy of the MDT decision and (modifications of) risk-stratification tools on justified ICU admissions were analyzed by backward stepwise multivariate logistic regression analysis.ResultsPre-operatively, the MDT decided a planned ICU admission in 38% of all 232 CAWR patients. Intra-operative events changed the MDT decision in 15% of all CAWR patients. MDT overestimated ICU need in 45% of ICU planned patients and underestimated in 10% of nursing ward planned patients. Ultimately, 42% went to the ICU and 27% of all 232 CAWR patients were justified ICU patients. MDT accuracy was higher than the Fischer score, HPW classification or any modification of these risk stratification tools.ConclusionA MDT's decision for a planned ICU admission after complex abdominal wall reconstruction was more accurate than any of the other risk-stratifying tools. Fifteen percent of the patients experienced unexpected operative events that changed the MDT decision. This study demonstrated the added value of a MDT in the care pathway of patients with complex abdominal wall hernias.

Background & Aims: The role of nutrition in modulating the inflammatory response is increasingly recognized. The phytonutrient sulforaphane shows promise for clinical use due to its effect on inflammatory pathways, favorable pharmacokinetic profile, and high bioavailability. The inflammatory status has been linked to autonomic activity, which can be assessed by the study of heart rate variability (HRV). However, monitoring of HRV for assessment of inflammation in humans has hardly been used. We investigated the potential of HRV as a non-invasive tool to monitor inflammation induced by the caloric load and assessed the effects of sulforaphane on caloric load-induced inflammation in healthy participants. Methods: In this double-blind, crossover, randomized, placebo-controlled trial twelve healthy participants (26.9 (3.6) years) were administered 25 mg of sulforaphane, or placebo followed over 90 min by the standardized high-calorie drink PhenFlex given to induce an inflammatory response. Levels of high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 were measured in plasma before and two hours after the PhenFlex challenge. Changes in the autonomic function were assessed by HRV on four timepoints. Results: The caloric challenge triggered a significant increase in total power (TP) (P = 0.028) and very low frequency (VLF) component (P = 0.013) 30 min after its administration. Those changes were followed by reduction of TP (P = 0.028) and low frequency (LF) component (P = 0.005), suggesting marked decrease in the sympathetic activity two hours after the caloric load. When sulforaphane was given prior to the caloric challenge, decreased parasympathetic activity was observed via a reduction of RMSSD (P = 0.007), pNN50 (P = 0.013) and HF (P = 0.047). In addition, sulforaphane elicited a pro-inflammatory response as measured by the change of hs-CRP with caloric exposure (sulforaphane 2.7 (4.2) vs. placebo -1.8 (3.1) ng/mL, P = 0.048). The pro-inflammatory effect of sulforaphane was associated with vagal withdrawal and sympathetic dominance as suggested by correlations between the changes in hs-CRP and HF (rs = -0.68, P = 0.029) as well as LF/HF (rs = 0.56, P = 0.093) components assessed before and two hours after the PhenFlex challenge. Conclusions: Monitoring of HRV might be a sensitive tool to follow activity of the inflammatory response in various clinical conditions. The standardized caloric PhenFlex challenge induced significant changes in the autonomic regulation in healthy young individuals. Administration of sulforaphane prior to the caloric challenge caused a pro-inflammatory effect which was accompanied by vagal withdrawal and sympathetic dominance. Trial registration number: NCT05146804 at www.clinicaltrials.gov.

Aim: To assess the added value of Near InfraRed Fluorescence (NIRF) imaging during laparoscopic cholecystectomy. Methods: This international multicentre randomized controlled trial included participants with an indication for elective laparoscopic cholecystectomy. Participants were randomised into a NIRF imaging assisted laparoscopic cholecystectomy (NIRF-LC) group and a conventional laparoscopic cholecystectomy (CLC) group. Primary end point was time to ‘Critical View of Safety’ (CVS). The follow-up period of this study was 90 postoperative days. An expert panel analysed the video recordings after surgery to confirm designated surgical time points. Results: A total of 294 patients were included, of which 143 were randomized in the NIRF-LC and 151 in the CLC group. Baseline characteristics were equally distributed. Time to CVS was on average 19 min and 14 s for the NIRF-LC group and 23 min and 9 s for the CLC group (p 0.032). Time to identification of the CD was 6 min and 47 s and 13 min for NIRF-LC and CLC respectively (p < 0.001). Transition of the CD in the gallbladder was identified after an average of 9 min and 39 s with NIRF-LC, compared to 18 min and 7 s with CLC (p < 0.001). No difference in postoperative length of hospital stay nor occurrence of postoperative complications was found. ICG related complications were limited to one patient who developed a rash after injection of ICG. Conclusion: Use of NIRF imaging in laparoscopic cholecystectomy provides earlier identification of relevant extrahepatic biliary anatomy: earlier achievement of CVS, cystic duct visualisation and visualisation of both cystic duct and cystic artery transition into the gallbladder.

PURPOSE: Obstructive sleep apnea (OSA) is highly prevalent but mostly undiagnosed in obese patients scheduled for bariatric surgery. To prevent cardiopulmonary complications, many clinics perform preoperative OSA screening. Consequently, adequate adherence to continuous positive airway pressure (CPAP) therapy is essential but challenging. We aimed to evaluate CPAP adherence and its influence on postoperative outcomes.METHODS: In a prospective multicenter cohort study, we compared different perioperative strategies for handling undiagnosed OSA in bariatric patients. In this subgroup analysis, patients newly diagnosed with OSA were compared to those with pre-existing OSA. We assessed inadequate CPAP adherence, defined as RESULTS: In total, 272 patients with newly diagnosed OSA (67.4%) and 132 patients with pre-existing OSA (32.6%) were included. Before surgery, 41 newly diagnosed patients used CPAP inadequately, compared to 5 patients with pre-existing OSA (15% vs. 4%, p = 0.049). Six months after surgery, inadequate CPAP use increased to 73% for newly diagnosed patients and 39% for patients with pre-existing OSA, respectively (p CONCLUSION: Inadequate CPAP adherence is higher in bariatric patients newly diagnosed with OSA when compared to patients with pre-existing OSA. Strategies to increase CPAP adherence may be valuable when considering routine OSA screening and CPAP therapy in patients undergoing bariatric surgery. Further studies are needed to improve current guidelines on perioperative OSA management of obese patients.TRIAL REGISTRATION: POPCORN study, registered at Netherlands Trial Register, https://www.trialregister.nl/trial/6805 . ID no: 6805.

Background Autologous fat transfer (AFT) seems to be a new minimal invasive method for total breast reconstruction, yet how patients, surgeons, and laymen evaluate cosmesis is lacking. The aim of this study was to evaluate the aesthetic outcome of AFT (intervention group) for total breast reconstruction post-mastectomy, as compared to implant-based reconstruction (IBR) (control group). Methods A random and blinded 3D photographic aesthetic outcome study was performed on a selection of 50 patients, scored by three panels: plastic surgeons, breast cancer patients, and laymen. Secondary outcomes included agreement within groups and possible patient characteristics influencing scoring. Results Breast cancer patients and plastic surgeons did not differ in the aesthetic scores between the treatment groups. In contrast, the laymen group scored AFT patients lower than IBR patients (− 1.04, p Conclusion Evaluation of aesthetic outcomes varies greatly. Hence, aesthetic outcome remains a very personal measure and this emphasizes the importance of thorough patient counseling including information on achievable aesthetic results before starting a reconstructive procedure. Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Background Disseminated disease (DD) is often found at (re-)exploration in gallbladder cancer (GBC) patients. We aimed to assess the yield of staging laparoscopy (SL) and identify predictors for DD. Methods This retrospective study included patients from all Dutch academic centres with primary GBC (pGBC) and incidentally diagnosed GBC (iGBC) planned for (re-)resection. The yield of SL was determined. In iGBC, predictive factors for DD were assessed. Results In total, 290 patients were included. Of 183 included pGBC patients, 143 underwent laparotomy without SL, and 42 (29%) showed DD perioperatively. SL, conducted in 40 patients, identified DD in eight. DD was found in nine of 32 patients who underwent laparotomy after SL. Of 107 included iGBC patients, 100 underwent laparotomy without SL, and 19 showed DD perioperatively. SL, conducted in seven patients, identified DD in one. Cholecystitis (OR = 4.25; 95% CI 1.51–11.91) and primary R1/R2 resection (OR = 3.94; 95% CI 1.39–11.19) were independent predictive factors for DD. Conclusions In pGBC patients, SL may identify DD in up to 20% of patients and should be part of standard management. In iGBC patients, SL is indicated after primary resection for cholecystitis and after initial R1/R2 resection due to the association of these factors with DD.

Background/ObjectiveCompelling evidence indicates that myokines act in an autocrine, paracrine and endocrine manner to alter metabolic homeostasis. The mechanisms underlying exercise-induced changes in myokine secretion remain to be elucidated. Since exercise acutely decreases oxygen partial pressure (pO(2)) in skeletal muscle (SM), the present study was designed to test the hypothesis that (1) hypoxia exposure impacts myokine secretion in primary human myotubes and (2) exposure to mild hypoxia in vivo alters fasting and postprandial plasma myokine concentrations in humans.MethodsDifferentiated primary human myotubes were exposed to different physiological pO(2) levels for 24 h, and cell culture medium was harvested to determine myokine secretion. Furthermore, we performed a randomized single-blind crossover trial to investigate the impact of mild intermittent hypoxia exposure (MIH: 7-day exposure to 15% O-2, 3x2h/day vs. normoxia: 21% O-2) on in vivo SM pO(2) and plasma myokine concentrations in 12 individuals with overweight and obesity (body-mass index >= 28 kg/m(2)).ResultsHypoxia exposure (1% O-2) increased secreted protein acidic and rich in cysteine (SPARC, p = 0.043) and follistatin like 1 (FSTL1, p = 0.021), and reduced leukemia inhibitory factor (LIF) secretion (p = 0.009) compared to 3% O-2 in primary human myotubes. In addition, 1% O-2 exposure increased interleukin-6 (IL-6, p = 0.004) and SPARC secretion (p = 0.021), whilst reducing fatty acid binding protein 3 (FABP3) secretion (p = 0.021) compared to 21% O-2. MIH exposure in vivo markedly decreased SM pO(2) (approximate to 40%, p = 0.002) but did not alter plasma myokine concentrations.ConclusionsHypoxia exposure altered the secretion of several myokines in primary human myotubes, revealing hypoxia as a novel modulator of myokine secretion. However, both acute and 7-day MIH exposure did not induce alterations in plasma myokine concentrations in individuals with overweight and obesity.

Contains fulltext : 293034.pdf (Publisher’s version ) (Open Access) OBJECTIVE: It is unknown whether ustekinumab (UST) levels can predict clinical outcomes in Crohn's disease (CD) patients. We assessed the exposure-response relationship of UST trough concentrations with biochemical outcomes at week 24 in a prospective, real-world setting. METHODS: We performed a prospective study in patients with CD starting UST in four academic centres in the Netherlands. All patients received a weight-adjusted intravenous (IV) UST induction dose, followed by one subcutaneous (SC) dose of 90 mg UST at 8 weeks. Maintenance therapy consisted of 90 mg subcutaneous UST every 8 or 12 weeks. Individual UST concentration time course during treatment were estimated using a population pharmacokinetic (PK) model. Quartile analysis and logistic regression were performed to analyse if UST concentrations at week 8 were associated with biochemical remission rates at week 24 (C-reactive protein (CRP) ≤ 5 mg/L and / or faecal calprotectin (FC) ≤ 250 mg/kg). RESULTS: In total, 124 patients with CD were included. Patients achieving biochemical remission at week 12 and 24 had significantly higher UST levels at week 8 compared to patients without biochemical remission (6.6 µg/mL versus 3.9 µg/mL, P

BACKGROUND: Risk-prediction tools can support doctor-patient (shared) decision making in clinical practice by providing information on complication risks for different types of bariatric surgery. However, external validation is imperative to ensure the generalizability of predictions in a new patient population.OBJECTIVE: To perform an external validation of the risk-prediction model for serious complications from the Michigan Bariatric Surgery Collaborative (MBSC) for Dutch bariatric patients using the nationwide Dutch Audit for Treatment of Obesity (DATO).SETTING: Population-based study, including all 18 hospitals performing bariatric surgery in the Netherlands.METHODS: All patients registered in the DATO undergoing bariatric surgery between 2015 and 2020 were included as the validation cohort. Serious complications included, among others, abdominal abscess, bowel obstruction, leak, and bleeding. Three risk-prediction models were validated: (1) the original MBSC model from 2011, (2) the original MBSC model including the same variables but updated to more recent patients (2015-2020), and (3) the current MBSC model. The following predictors from the MBSC model were available in the DATO: age, sex, procedure type, cardiovascular disease, and pulmonary disease. Model performance was determined using the area under the curve (AUC) to assess discrimination (i.e., the ability to distinguish patients with events from those without events) and a graphical plot to assess calibration (i.e., whether the predicted absolute risk for patients was similar to the observed prevalence of the outcome).RESULTS: The DATO validation cohort included 51,291 patients. Overall, 986 patients (1.92%) experienced serious complications. The original MBSC model, which was extended with the predictors "GERD (yes/no)," "OSAS (yes/no)," "hypertension (yes/no)," and "renal disease (yes/no)," showed the best validation results. This model had a good calibration and an AUC of .602 compared with an AUC of .65 and moderate to good calibration in the Michigan model.CONCLUSION: The DATO prediction model has good calibration but moderate discrimination. To be used in clinical practice, good calibration is essential to accurately predict individual risks in a real-world setting. Therefore, this model could provide valuable information for bariatric surgeons as part of shared decision making in daily practice.

BACKGROUND: Several pivotal studies and international guidelines on the perioperative management of rectal cancer have been published. However, little is known about the current state of perioperative management of rectal cancer patients in clinical practice worldwide.METHODS: An online survey including 13 questions focusing on key topics related to the perioperative management of patients with rectal cancer was conducted among colorectal surgeons registered within the database of the Research Institute Against Digestive Cancer (IRCAD).RESULTS: A total of 535 respondents from 89 countries participated in the survey. Most surgeons worked in the European region (40.9%). Two hundred and fifty-four respondents (47.5%) performed less than 25% of surgical procedures laparoscopically. The most commonly used definition of the upper limit of the rectum was a fixed distance from the anal verge (23.4%). Magnetic resonance imaging was used to define the upper limit of the rectum by 258 respondents (48.2%). During total mesorectal excision (TME), 301 respondents (56.3%) used a high-tie technique. The most commonly constructed anastomosis was an end-to-end anastomosis (68.2%) with the majority of surgeons performing a leak test intraoperatively (88.9%). A total of 355 respondents (66.4%) constructed a diverting ostomy, and the majority of these surgeons constructed an enterostomy (82%). A total of 208 respondents (39.3%) closed a stoma within 8 weeks. Lastly, 135 respondents (25.2%) introduced a solid diet on postoperative day 1.CONCLUSION: There is considerable heterogeneity in the perioperative management of rectal cancer patients worldwide with several discrepancies between current international practice and recommendations from international guidelines. To achieve worldwide standardization in rectal cancer care, further research is needed to elucidate the cause of this heterogeneity and find ways of improved implementation of best practice recommendations.

Journal of nephrology JN (2022). doi:10.1007/s40620-022-01454-2, Published by Springer, Milano

BACKGROUND AND AIMS: The DRAINAGE trial was a randomized controlled trial comparing preoperative endoscopic (EBD) and percutaneous biliary drainage (PTBD) in patients with potentially resectable, perihilar cholangiocarcinoma (pCCA). The aim of this study was to compare the long-term outcomes.METHODS: Patients were randomized in four tertiary referral centers. Follow-up data were available for all included patients. Primary outcome was overall survival (OS). Secondary outcomes were readmissions, and re-interventions not including in-trial interventions.RESULTS: A total of 54 patients were randomized; 27 in both groups. Median follow-up for both groups was 62 months (95% CI 54-70). The median OS was 13 months (95% CI 7.9-18.1) in the EBD and 7 months (95% CI 0.0-17.2) in the PTBD group (P = 0.28). Twenty (37%, n = 8 EBD vs n = 12 PTBD, P = 0.43) of 54 patients were readmitted at least once, mostly due to drainage-related complications (n = 13, 24%). Of note, 14 out of the 54 patients died within the trial. A total of 76 drainage procedures (32 EBD and 44 PTBD) were performed in 28 patients. The median number of stent or drain placements was 2 (2-4) for the EBD group and 2 (1-3) for the PTBD group (P = 0.77).DISCUSSION: Although this follow-up study represented a small cohort, no long-term differences in survival, readmissions, and drainage procedures for EBD and PTBD were found, even when comparing the resected and unresected group. However, this study demonstrates the complexity of biliary drainage for patients with potentially resectable pCCA, even in tertiary referral centers.

PURPOSE: To determine whether levels of pre-operative pain as recalled by a patient in the post-operative phase are possibly overestimated or underestimated compared to prospectively scored pain levels. If so, a subsequent misclassification may induce recall bias that may lead to an erroneous effect outcome.METHODS: Data of seven retrospective cohort studies on surgery for chronic abdominal wall and groin pain using three different pain scores were systematically analyzed. First, it was assessed whether retrospectively acquired pre-operative pain levels, as scored by the patient in the post-operative phase, differed from prospectively obtained pre-operative pain scores. Second, it was determined if errors associated with retrospectively obtained pain scores potentially lead to a misclassification of treatment outcome. Third, a meta-analysis established whether recall misclassifications, if present, affected overall study conclusions.RESULTS: Pain data of 313 patients undergoing remedial surgery were evaluated. The overall prevalence of misclassification due to a recall error was 13.7%. Patients not benefitting from surgery ('failures') judged their pre-operative pain level as more severe than it actually was. In contrast, patients who were pain free after remedial surgery ('successes') underestimated pre-operative pain scores. Recall misclassifications were significantly more present in failures than in successful patients (odds ratio 2.4 [95% CI 1.2-4.8]).CONCLUSION: One in seven patients undergoing remedial groin surgery is misclassified on the basis of retrospectively obtained pre-operative pain scores (success instead of failure, or vice versa). Misclassifications are relatively more present in failures after surgery. Therefore, the effect size of a therapy erroneously depends on its success rate.

Objective Although increasing evidence suggests a central mechanism of action for sacral neuromodulation, the exact mechanism remains unclear. We set up a scanning paradigm to measure brain activation related to various stages of rectal filling using rectal balloon distention. Materials and Methods Six healthy volunteers underwent rectal balloon distention during MRI scanning at a 1.5T scanner with a Tx/Rx head coil. MR images were collected at four levels of distention: empty balloon (EB), first sensation volume (FSV), desire to defecate volume (DDV), maximum tolerable volume (MTV). Data were analyzed using BrainVoyager 20.4. Whole brain and ROI-based fixed-effects general linear model analyses were performed on the fMRI time-course data from all participants. Results Rectal filling until FSV evoked the most blood-oxygen-level-dependent responses in several clusters throughout the cortex, followed by the responses evoked by rectal filling until DDV. Interestingly, rectal filling until MTV evoked negative responses compared to baseline throughout the cortex. No negative side effects were found. Discussion This study shows that a standardized paradigm for functional MRI combined with rectal filling is feasible and safe in healthy volunteers and is ready to be used in fecal incontinent patients to assess whether their brain activity differs from healthy controls.

Background: Perioperative music can have beneficial effects on postoperative pain and perioperative opioid requirement. This study aims to assess the implementation feasibility of music in day care surgery through adherence to implementation, as well as its effects. Methods: This implementation study employed a prospective single-center study design. Perioperative music was implemented as part of standard surgical care during day care surgery procedures. The music intervention consisted of preselected playlists. Primary outcome was adherence to implementation. Barriers and attitudes towards music of patients and perioperative care providers were evaluated. Furthermore, the effects of music were assessed through a matched cohort analysis. This study was registered with the Netherlands Trial Register (NL8213). Results: From January to April 2020, a total of 109 patients received the music intervention and 97 were analyzed after matching to retrospective controls. Adherence rate to the music intervention was 92% preoperatively, 81% intraoperatively, and 86% postoperatively, with 83% of patients satisfied with the preselected music, and 93% finding music to be beneficial to surgical care. All health care providers believed perioperative music to be beneficial (63%) or were neutral (37%) towards its use. Postoperative pain was not significantly different (mean numeric rating scale 0.74; the music intervention group versus 0.68; control group, p =.363). Although not statistically significant, postoperative opioid requirement in the music group was lower (30% versus 40%, p =.132). Conclusion: Perioperative music implementation in day care surgery is feasible with high adherence rates, patient satisfaction levels, and positive attitudes of health care providers towards its use.

Contains fulltext : 292877.pdf (Publisher’s version ) (Open Access)

Frans Houwen,1 Johannes Stemkens,2 Don van Sonsbeek,3 Robby van Sonsbeek,3 René van der Hulst,4 Herman van Langen5 1Peracutus B.V., Kronenberg, the Netherlands; 2Stemkens.Com B.V., Roggel, the Netherlands; 3D-Sight B.V., Maastricht, the Netherlands; 4Department of Plastic and Reconstructive Surgery, Maastricht University Medical Center+, Maastricht, the Netherlands; 5Department of Medical Physics and Devices, VieCuri Medical Centre, Venlo, the NetherlandsCorrespondence: Frans Houwen, Peracutus B.V., Peelstraat 4a, Kronenberg, 5976 NL, the Netherlands, Tel +31-650234240, Email frans.houwen@peracutus.comPurpose: High accuracy volume measurements have important implications in different medical and non-medical situations. All methods used to date have challenges to achieve a usable clinical accuracy. Moreover, current methods have limitations to measure segmental volumes. We developed a new device that is able to measure a continuous profile of the cross-sectional areas along an object. Herewith the total volume of an object or any part of it are correspondingly determined.Methods: The Peracutus Aqua Meth (PAM) generates continuous profiles of cross-sectional areas. Water is pumped in or out of a measuring unit at a nearly fixed flow rate and the speed of the water level (dh/dt) is measured continuously using a pressure sensor at the bottom. The change of the water level is a measure for the cross-sectional area of an object at any height. Signal processing is required to obtain valuable measurements. Three static objects and an arm of a test object were measured to demonstrate the accuracy and repeatability of the new device.Results: Cross-sectional areas of a PVC pipe obtained with the PAM and with a caliper were compared. The differences between the two methods were less than 1.3%. Volume measurements of two mannequin arms show standard deviations of 0.37% and 0.34%, respectively, whereas the standard deviation of the volume measurement of a genuine arm was only 1.07%. These figures surpass reported clinical accuracy.Conclusion: The new device demonstrates that determining the cross-section and its volumes of objects is possible in an accurate, reliable, and objective way. The results show that segmental volume measurements of human limbs are possible. Application in clinical and non-clinical situations seems meaningful.Keywords: volumetric, continuous profile, local volume, usable accuracy, objective

Pulmonary edema is a central hallmark of acute respiratory distress syndrome (ARDS). Endothelial dysfunction and epithelial injury contribute to alveolar-capillary permeability but their differential contribution to pulmonary edema development remains understudied. Plasma levels of surfactant protein-D (SP-D), soluble receptor for advanced glycation end products (sRAGE), and angiopoietin-2 (Ang-2) were measured in a prospective, multicenter cohort of invasively ventilated patients. Pulmonary edema was quantified using the radiographic assessment of lung edema (RALE) and global lung ultrasound (LUS) score. Variables were collected within 48 h after intubation. Linear regression was used to examine the association of the biomarkers with pulmonary edema. In 362 patients, higher SP-D, sRAGE, and Ang-2 concentrations were significantly associated with higher RALE and global LUS scores. After stratification by ARDS subgroups (pulmonary, nonpulmonary, COVID, non-COVID), the positive association of SP-D levels with pulmonary edema remained, whereas sRAGE and Ang-2 showed less consistent associations throughout the subgroups. In a multivariable analysis, SP-D levels were most strongly associated with pulmonary edema when combined with sRAGE (RALE score: βSP-D = 6.79 units/log10 pg/mL, βsRAGE = 3.84 units/log10 pg/mL, R2 = 0.23; global LUS score: βSP-D = 3.28 units/log10 pg/mL, βsRAGE = 2.06 units/log10 pg/mL, R2 = 0.086), whereas Ang-2 did not further improve the model. Biomarkers of epithelial injury and endothelial dysfunction were associated with pulmonary edema in invasively ventilated patients. SP-D and sRAGE showed the strongest association, suggesting that epithelial injury may form a final common pathway in the alveolar-capillary barrier dysfunction underlying pulmonary edema.

In pectus excavatum, three-dimensional (3D) surface imaging provides an accurate and radiation-free alternative to computed tomography (CT) to determine severity. Yet, it does not allow for cardiac evaluation since 3D imaging solely captures the chest wall surface. The objective was to develop a 3D image-based prediction model for cardiac compression in patients evaluated for pectus excavatum. A prospective cohort study was conducted including consecutive patients referred for pectus excavatum who received a thoracic CT. Additionally, 3D images were acquired. The external pectus depth, its length, craniocaudal position, cranial slope, asymmetry, anteroposterior distance and chest width were calculated from 3D images. Together with baseline patient characteristics they were submitted to forward multivariable logistic regression to identify predictors for cardiac compression. Cardiac compression on CT was used as reference. The model's performance was depicted by the area under the receiver operating characteristic (AUROC) curve. Internal validation was performed using bootstrapping. Sixty-one patients were included of whom 41 had cardiac compression on CT. A combination of the 3D image derived external pectus depth and external anteroposterior distance was identified as predictive for cardiac compression, yielding an AUROC of 0.935 (95% confidence interval [CI]: 0.878-0.992) with an optimism of 0.006. In a second model for males alone, solely the external pectus depth was identified as predictor, yielding an AUROC of 0.947 (95% CI: 0.892-1.000) with an optimism of 0.0002. We have developed two 3D image-based prediction models for cardiac compression in patients evaluated for pectus excavatum which provide an outstanding discriminatory performance between the presence and absence of cardiac compression with negligible optimism.

BACKGROUND AND AIMS: Autoimmune liver diseases (AILDs) are associated with impaired health-related quality of life (HrQoL). The aim of this project was to identify potentially modifiable factors related to HrQoL in a large transnational cohort of patients with AILDs.METHODS: A cross-sectional online survey was conducted on patients with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) or primary sclerosing cholangitis from 15 European countries. HrQoL was measured with EQ-5D-5L and EQ visual analogue scale (EQ-VAS) and analysed in relation to demographic, psychosocial, disease- and treatment-related factors. A Patient Health Questionnaire-2 score >3 indicated relevant depression. Multivariable linear regression analyses were used to identify potentially modifiable factors associated with HrQoL and confidence in treatment whilst adjusting for known confounders.RESULTS: A group of 1178 European patients (79% female, mean age 48 ± 14 years) participated in the study. HrQoL was impaired in all three diseases (mean EQ-5D-5L = 0.75, mean EQ VAS = 68.9), most markedly in PBC (mean EQ-5D-5L = 0.73, mean EQ-VAS = 66.2). Relevant depression, which was detected in 17% of patients, was prominently associated with impaired HrQoL. In the regression analysis, treatment confidence was identified as an important modifiable factor positively contributing to HrQoL. This influence was observable even after adjusting for other covariates including depression. Management in a transplant centre, treatment with azathioprine in AIH, and with ursodeoxycholic acid in PBC, was associated with increased treatment confidence. Finally, improved patient-physician relationships contributed to treatment confidence.CONCLUSION: Treatment confidence is a relevant modifiable determinant of HrQoL and should be further investigated to improve the standards of care for patients with AILDs.

Not available.

Background: The use and effect of most infection control measures (ICMs) in breast implant surgery are still debated, likely resulting in undesired variation in current practices. Objectives: This study investigated the relationship between the number and combinations of ICMs used and the infection-related revision incidence after breast implant surgery. Additionally, national variation between Dutch healthcare institutions in ICM use was evaluated. Methods: For this multicentre, population-based study, all patients who received a primary breast implant or tissue expander for breast augmentation or reconstruction between 2015 and 2019 were identified from the Dutch Breast Implant Registry. Seven prospectively collected ICMs were investigated: preoperative antibiotics, implant and/or pocket irrigation, glove change, nipple guards, insertion sleeve, postoperative drains, and postoperative antibiotics. Results: This study included 52,415 implants (85% augmentation, 15% reconstruction).The median (IQR) number of ICMs used was 3 (3-4) for augmentation and 4 (4-5) for reconstruction. Median follow-up was 30 months for augmentation and 34 months for reconstruction. Infection-related revision incidence was 0.1% for augmentation and 2.1% for reconstruction. Most infection-related revisions occurred within 2 months for augmentation and 2.5 months for reconstruction. The impact of ICM use on infection-related revision incidence remained unclear, given its low incidence. A significant variation was observed between institutions in the use of postoperative antibiotics and drains. Conclusions: Although the use of different ICMs varied considerably between institutions, the infection-related revision incidence after breast implant surgery was generally low. Most surgeons used four ICMs for breast reconstruction and three ICMs for breast augmentation. Further studies on the causes and effects of the observed variation are needed. (c) 2022The Author(s). Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons.

BACKGROUND: Published empirical data have increasingly suggested that using near-infrared fluorescence cholangiography during laparoscopic cholecystectomy markedly increases biliary anatomy visualization. The technology is rapidly evolving, and different equipment and doses may be used. We aimed to identify areas of consensus and nonconsensus in the use of incisionless near-infrared fluorescent cholangiography during laparoscopic cholecystectomy.METHODS: A 2-round Delphi survey was conducted among 28 international experts in minimally invasive surgery and near-infrared fluorescent cholangiography in 2020, during which respondents voted on 62 statements on patient preparation and contraindications (n = 12); on indocyanine green administration (n = 14); on potential advantages and uses of near-infrared fluorescent cholangiography (n = 18); comparing near-infrared fluorescent cholangiography with intraoperative x-ray cholangiography (n = 7); and on potential disadvantages of and required training for near-infrared fluorescent cholangiography (n = 11).RESULTS: Expert consensus strongly supports near-infrared fluorescent cholangiography superiority over white light for the visualization of biliary structures and reduction of laparoscopic cholecystectomy risks. It also offers other advantages like enhancing anatomic visualization in obese patients and those with moderate to severe inflammation. Regarding indocyanine green administration, consensus was reached that dosing should be on a milligrams/kilogram basis, rather than as an absolute dose, and that doses >0.05 mg/kg are necessary. Although there is no consensus on the optimum preoperative timing of indocyanine green injections, the majority of participants consider it important to administer indocyanine green at least 45 minutes before the procedure to decrease the light intensity of the liver.CONCLUSION: Near-infrared fluorescent cholangiography experts strongly agree on its effectiveness and safety during laparoscopic cholecystectomy and that it should be used routinely, but further research is necessary to establish optimum timing and doses for indocyanine green.

The surgical treatment of parastomal hernias is considered complex and is known to be prone to complications. Traditionally, this condition was treated using relocation techniques or local suture repairs. Since then, several mesh-based techniques have been proposed and are nowadays used in minimally invasive surgery. Since the introduction of robot-assisted surgery to the field of abdominal wall surgery, several adaptations to these techniques have been made, which may significantly improve patient outcomes. In this contribution, we provide an overview of available techniques in robot-assisted parastomal hernia repair. Technical considerations and preliminary results of robot-assisted modified Sugarbaker repair, robot-assisted Pauli technique, and minimally invasive use of a funnel-shaped mesh in the treatment of parastomal hernias are presented. Furthermore, challenges in robot-assisted ileal conduit parastomal hernia repair are discussed. These techniques are illustrated by photographic and video material. Besides providing a comprehensive overview of robot-assisted parastomal hernia repair, this article focuses on the specific advantages of robot-assisted techniques in the treatment of this condition.Die chirurgische Behandlung parastomaler Hernien gilt als komplex und ist bekanntermaßen komplikationsträchtig. In der Vergangenheit wurden diese Hernien durch die Relokation des Stomas oder Nahtverfahren der Austrittstelle versorgt. In den letzten Jahren wurden verschiedene netzbasierte Techniken vorgeschlagen, die heute in der minimal-invasiven Chirurgie eingesetzt werden. Mit der Verbreitung der roboterassistierten Hernienchirurgie wurden die Netzverfahren weiterentwickelt und die Ergebnisse für die Patienten erheblich verbessert. In diesem Beitrag wird ein Überblick über die verfügbaren Techniken der roboterassistierten Versorgung parastomaler Hernien präsentiert. Es werden technische Überlegungen und erste Ergebnisse des roboterassistierten modifizierten Sugarbaker-Verfahrens, der roboterassistierten Pauli-Technik und der Verwendung des trichterförmigen Netzes IPST vorgestellt. Darüber hinaus werden die Herausforderungen bei der roboterassistierten Versorgung parastomaler Hernien am Ileum-Conduit diskutiert. Die Operationstechniken werden durch Foto- und Videomaterial veranschaulicht.

BACKGROUND: Approximately 25% of patients with inflammatory bowel disease (IBD) discontinue azathioprine (AZA) or mercaptopurine (MP) therapy within 3 months of treatment initiation due to adverse drug reactions. Of these side-effects, about half are due to hepatotoxicity.The aim of this study was to validate and (subsequently) optimize a previously reported predictive algorithm for thiopurine-associated hepatotoxicity by increasing the number of patients with IBD benefitting from conventional thiopurine therapy.METHODS: This multicenter observational study included consecutive thiopurine-naive patients with IBD who received AZA or MP treatment. The primary outcome was hepatotoxicity within 12 weeks. The patients with and without hepatotoxicity were compared. Four determinants, namely, age, sex, body mass index (BMI), and 6-methylmercaptopurine ribonucleotide (6-MMPR) concentrations 1 week after treatment initiation (T = 1) were used to validate and optimize two (one dichotomous and one continuous) algorithms using multivariable logistic regression analysis.RESULTS: Of 229 patients, 21 (9%) developed hepatotoxicity and 93% of the patients received MP with a median dose of 0.7 mg/kg (95% CI 0.3-1.4 mg/kg). A difference in BMI was found between with and without hepatotoxicity groups (median 27.6 versus 24.2, p = 0.022). Specificities of 68% (Algorithm 1) and 77% (Algorithm 2) and sensitivities of 56% (Algorithm 1) and 50% (Algorithm 2) were obtained.CONCLUSION: Both algorithms demonstrated limited predictive accuracy for thiopurine-induced hepatotoxicity in the validation cohort. Relevant factors contributing to this outcome were changes in thiopurine prescription behavior over time, with more MP prescriptions at relatively lower dosages of MP.

BACKGROUND: In recent years, indocyanine green angiography (ICG-A) has been used increasingly to assist tissue perfusion assessments during plastic and reconstructive surgery procedures, but no guidelines exist regarding its use. We sought to identify areas of consensus and non-consensus among international experts on the use of ICG-A for tissue-perfusion assessments during plastic and reconstructive surgery.METHODS: A two-round, online Delphi survey was conducted of 22 international experts from four continents asking them to vote on 79 statements divided into five modules: module 1 = patient preparation and contraindications (n = 11 statements); module 2 = ICG administration and camera settings (n = 17); module 3 = other factors impacting perfusion assessments (n = 10); module 4 = specific indications, including trauma debridement (n = 9), mastectomy skin flaps (n = 6), and free flap reconstruction (n = 8); and module 5 = general advantages and disadvantages, training, insurance coverage issues, and future directions (n = 18). Consensus was defined as ≥70% inter-voter agreement.RESULTS: Consensus was reached on 73/79 statements, including the overall value, advantages, and limitations of ICG-A in numerous surgical settings; also, on the dose (0.05 mg/kg) and timing of ICG administration (∼20-60 seconds preassessment) and best camera angle (61-90o) and target-to-tissue distance (20-30 cm). However, consensus also was reached that camera angle and distance can vary, depending on the make of camera, and that further research is necessary to technically optimize this imaging tool. The experts also agreed that ambient light, patient body temperature, and vasopressor use impact perfusion assessments.CONCLUSION: ICG-A aids perfusion assessments during plastic and reconstructive surgery and should no longer be considered experimental. It has become an important surgical tool.

During the COVID-19 pandemic, a 13.6 per cent reduction in the number of surgical procedures performed was observed in 2020. Despite great pressure on healthcare, the COVID-19 pandemic did not cause an increase in adverse surgical outcomes, and oncological surgery-related duration of hospital and ICU stay were significantly shorter.Background The COVID-19 pandemic caused disruption of regular healthcare leading to reduced hospital attendances, repurposing of surgical facilities, and cancellation of cancer screening programmes. This study aimed to determine the impact of COVID-19 on surgical care in the Netherlands. Methods A nationwide study was conducted in collaboration with the Dutch Institute for Clinical Auditing. Eight surgical audits were expanded with items regarding alterations in scheduling and treatment plans. Data on procedures performed in 2020 were compared with those from a historical cohort (2018-2019). Endpoints included total numbers of procedures performed and altered treatment plans. Secondary endpoints included complication, readmission, and mortality rates. Results Some 12 154 procedures were performed in participating hospitals in 2020, representing a decrease of 13.6 per cent compared with 2018-2019. The largest reduction (29.2 per cent) was for non-cancer procedures during the first COVID-19 wave. Surgical treatment was postponed for 9.6 per cent of patients. Alterations in surgical treatment plans were observed in 1.7 per cent. Time from diagnosis to surgery decreased (to 28 days in 2020, from 34 days in 2019 and 36 days in 2018; P < 0.001). For cancer-related procedures, duration of hospital stay decreased (5 versus 6 days; P < 0.001). Audit-specific complications, readmission, and mortality rates were unchanged, but ICU admissions decreased (16.5 versus 16.8 per cent; P < 0.001). Conclusion The reduction in the number of surgical operations was greatest for those without cancer. Where surgery was undertaken, it appeared to be delivered safely, with similar complication and mortality rates, fewer admissions to ICU, and a shorter hospital stay.Lay Summary COVID-19 has had a significant impact on healthcare worldwide. Hospital visits were reduced, operating facilities were used for COVID-19 care, and cancer screening programmes were cancelled. This study describes the impact of the COVID-19 pandemic on Dutch surgical healthcare in 2020. Patterns of care in terms of changed or delayed treatment are described for patients who had surgery in 2020, compared with those who had surgery in 2018-2019. The study found that mainly non-cancer surgical treatments were cancelled during months with high COVID-19 rates. Outcomes for patients undergoing surgery were similar but with fewer ICU admissions and shorter hospital stay. These data provide no insight into the burden endured by patients who had postponed or cancelled operations.

BACKGROUND: Despite exponentially growing evidence supporting the use of intraoperative fluorescence imaging + indocyanine green dye, considerable variability exists in how and when it is used, and no published consensus guidelines exist. We have conducted Delphi surveys of international experts in the use of intraoperative fluorescence imaging covering 6 distinct surgical scenarios: laparoscopic cholecystectomy; colorectal, lymphedema, gastric cancer, and plastic surgery; and thyroid and parathyroid resections. Although each survey asked experts to vote on field-specific consensus statements, they also had 29 shared statements to permit some analysis spanning the 6 specialties. This article summarizes these results.METHODS: Data on the 29 shared statements from 6 two-round Delphi consensus surveys were compiled to identify areas of overall consensus and compare the different specialties. As with the individual surveys, consensus was defined as ≥70% intervoter agreement.RESULTS: Among 140 participating experts, overall consensus was achieved on 16 statements, including strong agreement that using indocyanine green is extremely safe, that it can be used even when informed written consent cannot be provided, that it significantly enhances anatomical visualization and impacts how procedures are performed, and that it significantly reduces overall procedural risk. However, indocyanine green dosing and timing are procedure-specific, with considerable variability persisting for some applications, and the overall consensus is that further research is necessary to optimize this facet of intraoperative fluorescence imaging.CONCLUSION: Fluorescence imaging is gaining traction across multiple surgical specialties as an invaluable intraoperative tool. Its use in clinical practice and research seems destined to increase.

BACKGROUND & AIMS: Previous single-cell RNA-sequencing analyses have shown that Trem2-expressing macrophages are present in the liver during obesity, non-alcoholic steatohepatitis (NASH) and cirrhosis. Herein, we aimed to functionally characterize the role of bone marrow-derived TREM2-expressing macrophage populations in NASH.METHODS: We used bulk RNA sequencing to assess the hepatic molecular response to lipid-dependent dietary intervention in mice. Spatial mapping, bone marrow transplantation in two complementary murine models and single-cell sequencing were applied to functionally characterize the role of TREM2+ macrophage populations in NASH.RESULTS: We found that the hepatic transcriptomic profile during steatohepatitis mirrors the dynamics of recruited bone marrow-derived monocytes that already acquire increased expression of Trem2 in the circulation. Increased Trem2 expression was reflected by elevated levels of systemic soluble TREM2 in mice and humans with NASH. In addition, soluble TREM2 levels were superior to traditionally used laboratory parameters for distinguishing between different fatty liver disease stages in two separate clinical cohorts. Spatial transcriptomics revealed that TREM2+ macrophages localize to sites of hepatocellular damage, inflammation and fibrosis in the steatotic liver. Finally, using multiple murine models and in vitro experiments, we demonstrate that hematopoietic Trem2 deficiency causes defective lipid handling and extracellular matrix remodeling, resulting in exacerbated steatohepatitis, cell death and fibrosis.CONCLUSIONS: Our study highlights the functional properties of bone marrow-derived TREM2+ macrophages and implies the clinical relevance of systemic soluble TREM2 levels in the context of NASH.LAY SUMMARY: Our study defines the origin and function of macrophages (a type of immune cell) that are present in the liver and express a specific protein called TREM2. We find that these cells have an important role in protecting against non-alcoholic steatohepatitis (a progressive form of fatty liver disease). We also show that the levels of soluble TREM2 in the blood could serve as a circulating marker of non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a highly prevalent, chronic disorder of the gut-brain interaction that significantly affects quality of life. Several treatments, with comparable clinical efficacy, are available. Patient preferences can therefore be an important determinant of an effective management strategy. Treatment preferences of patients regarding decision making remain unclear. We aimed to examine these preferences and estimate trade-offs between different attributes.METHODS: A total of 427 patients from the Maastricht IBS cohort were invited to participate. A labeled discrete choice experiment survey, containing 9 scenarios with each 3 alternatives (medication, diet, psychotherapy), was developed in order to estimate preferences. The treatment scenarios were based on 6 attributes: effectiveness, time to response, time until recurrence, side effects, time required, and frequency of appointments. The preference weights and relative importance were analyzed using a mixed logit model.RESULTS: A total of 185 (43.3%) of 427 potential respondents completed the questionnaire (mean age 49.51 years, 69.2% female). The most preferred treatment was dietary intervention (48.1%), followed by pharmacotherapy (29.2%) and psychotherapy (22.7%). IBS patients preferred a higher effectiveness, shorter time interval to response, longer time interval until recurrence, no severe side effects, and frequent appointments when attending psychotherapy. Younger patients (50 years of age) were more inclined to choose pharmacotherapy and the period until recurrence was not important.CONCLUSIONS: Dietary interventions were the most preferred IBS therapy. Identifying patients' treatment preferences during shared decision making will provide more optimal management strategies and could be the best approach to diminish disease burden.

Background. Diagnosing and discriminating non-cardiogenic interstitial syndrome (NCIS) and cardiogenic pulmonary edema (CPE) is notoriously difficult in a mixed intensive care unit (ICU) population. We hypothesized that a comprehensive lung ultrasound exam can be used to accurately diagnose interstitial syndrome and can discriminate between NCIS and CPE.Methods. A single center prospective diagnostic accuracy study was used as derivation cohort and a post-hoc analysis of a multi-center prospective observational study as validation cohort. Consecutive adult ICU patients that received a lung ultrasound examination for clinical or study purposes were included. The reference standard was the diagnosis interstitial syndrome (NCIS or CPE) or non-interstitial syndromes (other pulmonary diagnoses and no pulmonary diagnoses) at the moment of examination based on full post-hoc clinical chart review except lung ultrasound. The index test was a comprehensive lung ultrasound examination performed and scored by a researcher blinded to clinical information.Results. 101 patients were included in the derivation and 125 in validation cohort. In the derivation cohort, patients with interstitial syndrome (n=56) were reliably discriminated from other patients based on the presence of a B-pattern (defined as ≥3 B-lines in one frame) with an accuracy of 94.7% (sens 90.9%, spec 91.1%), while specificity was higher for a bilateral B-pattern (accuracy 86.0%; sens 74.5%, spec 100%). For the discrimination of NCIS (n=29) from CPE (n=27), the presence of bilateral pleural line abnormalities had the highest diagnostic accuracy (94.6%; sens 89.3%, spec 100%) followed by consolidation (76.8%; sens 69.0%, spec 85.2%) and subtle lung sliding (67.9%; sens 62.1%, spec 74.1%). A diagnostic algorithm (BLUISH protocol) using B-pattern and bilateral pleural abnormalities had an accuracy of 0.86 (95%CI 0.77-0.95) for diagnosis and discrimination of interstitial syndromes. In the validation cohort, which included 125 patients with interstitial syndrome, pleural line abnormalities discriminated NCIS (n=101) from CPE (n=24) with a sensitivity of 30% (95%CI 21-40%) and a specificity of 100% (95%CI: 86-100%). Conclusions. Lung ultrasound can be used to diagnose and discriminate interstitial syndromes in ICU patients with moderate to good accuracy. Pleural line abnormalities are highly specific for NCIS, but sensitivity is limited.

Contains fulltext : 290620.pdf (Publisher’s version ) (Open Access) BACKGROUND: Tofacitinib is an oral Janus kinase (JAK) inhibitor and is registered for the treatment of ulcerative colitis (UC). The effectiveness of tofacitinib has been evaluated up to 12 months of treatment. AIM: The aim of this study was to assess the effectiveness and safety of 24 months of tofacitinib use in UC patients in the Netherlands. METHODS: Patients initiating tofacitinib treatment were included in the ICC Registry, a nationwide, observational registry. Patients were prospectively evaluated for up to 24 months. The primary outcome was corticosteroid-free clinical remission (CSFR, Simple Clinical Colitis Activity Index [SCCAI] ≤2) at week 104. Secondary outcomes included biochemical remission (C-reactive protein (CRP) ≤5 mg/L and faecal calprotectin (FC) ≤250 μg/g), safety, and discontinuation rate. RESULTS: We included 110 patients of whom 104 (94.5%) were anti-TNF experienced. After 104 weeks of tofacitinib, 31.8% (34/107) were in CSFR, 23.4% (25/107) in biochemical remission and 18.7% (20/107) in combined clinical and biochemical remission. Of the patients in CSFR at week 52, 76.5% (26/34) remained so after 104 weeks of treatment. Sixty-one patients (55.5%) discontinued tofacitinib after a median duration of 13 weeks (IQR 7-34). The main reasons for discontinuation were non-response (59%), loss of response (14.8%), and adverse events (18%). There were 33.9 possible tofacitinib-related adverse events per 100 patient-years during follow-up. Adverse events most probably related to tofacitinib were skin reactions and headaches. There were 6.4 herpes zoster infections per 100 patient-years. CONCLUSION: Tofacitinib was effective in 31.8% of patients after 24 months of treatment. 01 januari 2023

Results from high altitude studies in humans and controlled animal experiments suggest that hypoxia exposure induces alterations in gut microbiota composition, which may in turn affect host metabolism. However, well-controlled studies investigating the effects of normobaric hypoxia exposure on gut microbiota composition in humans are lacking. The aim of this study was to explore the impact of mild intermittent hypoxia (MIH) exposure on gut microbiota composition in men with overweight and/or obesity. We performed a randomised, single-blind crossover study, in which participants were exposed to MIH (FiO2: 15%, 3×2 h per day) and normoxia (FiO2: 21%) for seven consecutive days. Following the MIH and normoxia exposure regimens, faecal samples were collected for determination of faecal microbiota composition using 16S rRNA gene-amplicon sequencing in the morning of day 8. Paired faecal samples were available for five individuals. Furthermore, tissue-specific insulin sensitivity was determined using the gold-standard two-step hyperinsulinemic-euglycemic clamp. MIH did not affect microbial alpha and beta-diversity but reduced the relative abundance of Christensenellaceae and Clostridiaceae bacterial families. MIH significantly increased the abundances of obligate anaerobic bacterial genera including Fusicatenibacter, Butyricicoccus and Holdemania, whilst reducing Christensenellaceae R-7 group and Clostridium sensu stricto 1, although these findings were not statistically significant after correction for multiple testing. Furthermore, MIH-induced alterations in abundances of several genera were associated with changes in metabolic parameters such as adipose and peripheral insulin sensitivity, plasma levels of insulin, fatty acids, triacylglycerol and lactate, and substrate oxidation. In conclusion, we demonstrate for the first time that MIH exposure induces modest effects on faecal microbiota composition in humans, shifting several bacterial families and genera towards higher abundances of anaerobic butyrate-producing bacteria. Moreover, MIH-induced effects on faecal microbial composition were associated with parameters related to glucose and lipid homeostasis, supporting a link between MIH-induced alterations in faecal microbiota composition and host metabolism. The study was registered at the Netherlands Trial Register: NL7120/NTR7325.

Background Since the number of breast cancer genetic gene testing is increasing, more women opt for bilateral prophylactic mastectomy (BPM) followed by breast reconstruction. However, little is known about the differences in Quality of Life (QoL) after various reconstructive surgeries in this population. In this study, the long-term breast-related, body-related, and health-related QoL between immediate implant-based breast reconstruction (IBBR) and autologous breast reconstruction (ABR) were compared, in women who underwent BPM. Methods In this cross-sectional study, women who underwent postmastectomy breast reconstruction between January 2015 and December 2018 were invited for an online questionnaire, in which the BREAST-Q, the BODY-Q and the SF-36 were included. Women who underwent BPM and immediate breast reconstruction were included for analysis. Multivariable linear regression analysis was performed to adjust mean differences in patient-reported outcomes between IBBR and ABR for potential confounders. Results Of the included women (n = 47), 33 underwent ABR and 14 women underwent IBBR following BPM. BREAST-Q scores were in favor of the ABR group before and after adjustment, with statistically significance on Satisfaction with breasts (mean difference 15.8, p = 0.019) and Physical well-being (mean difference 13.5, p = 0.033). None of the mean differences in BODY-Q and SF-36 scores between groups, before and after adjustment, were statistically significant. Conclusion This study suggests that there is a higher satisfaction with breasts and better physical well-being in women who underwent immediate ABR compared to those who underwent immediate IBBR after BPM. However, these data should be interpreted carefully as a result of selection bias and a small sample size. Level of Evidence: Level III, risk study.

Increased exposure to ultraviolet radiation (UVR) is associated with an increased risk of nonmelanoma skin cancer. Cutaneous surgery can be negatively influenced by UVR, causing delayed wound healing, hyperpigmentation of the scar, and an increased incidence of additional skin cancers. By changing sun protection behavior, these risks can be limited. Therefore, this study evaluates changes in patients' sun protective behavior after Mohs micrographic surgery (MMS). Patients undergoing MMS between December 2017 and November 2019 were included. Patients were asked to complete the FACE-Q Skin Cancer - Sun Protection Behavior checklist before and 3 months and 1 year post-surgery. A total of 125 patients completed the pre-operative and 3-months post-operative checklists, and 89 (71.2%) completed the 1-year post-operative checklist. Reported sun protective behaviors increased post-surgery at all time points (p < 0.001). Patients with a prior history of facial skin cancer demonstrated a larger increase in sun protection behaviors after surgery than patients without a history of facial skin cancer (p = 0.04). Patients with defects located on the ear or scalp demonstrated a lesser increase in sun protection behaviors than patients with defects located in more conspicuous areas as the face (p = 0.02). Our study demonstrates a change in sun protection behavior, with an increase in sun protection behavior over time in patients after MMS. However, more improvement is possible. Targeted counseling can increase sun protection behavior in patients without a history of facial skin cancer and patients with skin cancer located on the ears or scalp.

Purpose Hospitals performing a certain bariatric procedure in high volumes may have better outcomes. However, they could also have worse outcomes for some patients who are better off receiving another procedure. This study evaluates the effect of hospital preference for a specific type of bariatric procedure on their overall weight loss results. Methods All hospitals performing bariatric surgery were included from the nationwide Dutch Audit for Treatment of Obesity. For each hospital, the expected (E) numbers of sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and one-anastomosis gastric bypass (OAGB) were calculated given their patient-mix. These were compared with the observed (O) numbers as the O/E ratio in a funnel plot. The 95% control intervals were used to identify outlier hospitals performing a certain procedure significantly more often than expected given their patient-mix (defined as hospital preference for that procedure). Similarly, funnel plots were created for the outcome of patients achieving ≥ 25% total weight loss (TWL) after 2 years, which was linked to each hospital’s preference. Results A total of 34,558 patients were included, with 23,154 patients completing a 2-year follow-up, of whom 79.6% achieved ≥ 25%TWL. Nine hospitals had a preference for RYGB (range O/E ratio [1.09–1.53]), with 1 having significantly more patients achieving ≥ 25%TWL (O/E ratio [1.06]). Of 6 hospitals with a preference for SG (range O/E ratio [1.10–2.71]), one hospital had significantly fewer patients achieving ≥ 25%TWL (O/E ratio [0.90]), and from two hospitals with a preference for OAGB (range O/E ratio [4.0–6.0]), one had significantly more patients achieving ≥ 25%TWL (O/E ratio [1.07]). One hospital had no preference for any procedure but did have significantly more patients achieving ≥ 25%TWL (O/E ratio [1.10]). Conclusion Hospital preference is not consistently associated with better overall weight loss results. This suggests that even though experience with a procedure may be slightly less in hospitals not having a preference, it is still sufficient to achieve similar weight loss outcomes when surgery is provided in centralized high-volume bariatric institutions. Graphical Abstract

Background A causal relation between systemic symptoms and breast implants has not been established. Psychological factors, such as personality and psychological distress, are strongly associated with the development of medically unexplained symptoms. It can be hypothesized that psychological factors may be related to the development of breast implant illness (BII). Objectives This study was conducted to evaluate the correlation between self-reported health complaints, health- and breast-related quality of life (QoL), and personality, in women with cosmetic breast implants. Methods Women who attended the plastic surgery outpatient clinic of Maastricht University Medical Center between October 2020 and October 2021 for reasons related to their implants and women recruited for a BII study at the Center during this period were invited to participate in this study. Only women who underwent cosmetic breast augmentation were eligible. Participants completed a physical complaints score form and the BREAST-Q, SF-36, and EPQ-RSS questionnaires via an online survey. Results In total, 201 women completed the questionnaires. Extroversion and social desirability were predominant personality traits in women with breast implants, followed by neuroticism. Relatively high levels of neuroticism were found compared with normative data. Neuroticism correlated significantly with health status and breast-related QoL. Physical and mental health–related QoL had the strongest correlations with neuroticism (β = −3.94, β = −4.86, P < 0.001). Conclusions Personality can play a role in the development of complaints. High levels of neuroticism are seen in cosmetic surgery patients and are negatively correlated with subjective health and patient-reported outcomes in women with breast implants. Therefore, neuroticism may be a factor in the development of BII. Level of Evidence: 4

BACKGROUND AND OBJECTIVES: This study aimed to explore colorectal cancer (CRC) patients' perspectives and experiences regarding the preoperative surgical care pathway and their subsequent preparedness for surgery and postoperative recovery.METHODS: CRC patients were recruited using purposive sampling and were interviewed three times (preoperatively, and 6 weeks and 3 months postoperatively) using semistructured telephone interviews. Interviews were audiotaped, transcribed verbatim and analysed independently by two researchers using thematic analysis with open coding.RESULTS: Data saturation was achieved after including 18 patients. Preoperative factors that contributed to a feeling of preparedness for surgery and recovery were patient-centred- and professional healthcare organization, sincere and personal guidance, and thorough information provision. Postoperatively, patients with complications or physical complaints experienced unmet information needs regarding the impact of complications and what to expect from postoperative recovery.CONCLUSIONS: The preoperative period is a vital period to prepare patients for surgery and recovery in which patients most value personalized information, personal guidance and professionalism. According to CRC patients, the feeling of preparedness for surgery and recovery can be improved by continually providing dosed information. This information should provide the patient with patient-tailored perspectives regarding the impact of (potential) complications and what to expect during recovery.

Objectives This study investigates whether a citrus and pomegranate complex (CPC) improves physical fitness, mental well-being, and blood biomarkers for oxidative stress and endothelial function in healthy elderly. Design A randomized placebo-controlled cross-over trial. Participants The study included 36 healthy elderly aged 60–75 years old. Intervention and Measurements Participants received four weeks of CPC supplementation and performed the handgrip strength and senior fitness test. Quality of life (QOL) was assessed and blood samples were analyzed for oxidative stress and endothelial function markers. Results After four weeks of CPC supplementation, handgrip strength significantly improved (p=0.019), compared to placebo. Moreover, the thinking, memory, learning, and concentration facets were improved (p=0.042), compared to placebo, and plasma malondialdehyde decreased, compared to placebo (p=0.033). The intervention did not affect senior fitness and the other QOL domains and blood parameters. Conclusion Four weeks of daily CPC supplementation significantly improves handgrip strength and self-evaluated measures of psychological function in healthy older adults. Further research should focus on mechanisms associated with physical performance.

Bile salt export pump (Bsep) (Abcb11)(-/-) mice are protected from acquired cholestatic injury due to metabolic preconditioning with a hydrophilic bile acid (BA) pool with formation of tetrahydroxylated bile acids (THBAs). We aimed to explore whether loss of Bsep and subsequent elevation of THBA levels may have immunomodulatory effects, thus improving liver injury in the multidrug resistance protein 2 (Mdr2) (Abcb4)(-/-) mouse. Cholestatic liver injury in Mdr2(-/-)Bsep(-/-) double knockout (DKO), Mdr2(-/-), Bsep(-/-), and wild-type mice was studied for comparison. Mdr2(-/-) mice were treated with a THBA (3 alpha,6 alpha,7 alpha,12 alpha-Tetrahydroxycholanoic acid). RNA/protein expression of inflammatory/fibrotic markers were investigated. Serum BA-profiling was assessed by ultra-performance liquid chromatography tandem mass spectrometry. Hepatic immune cell profile was quantified by flow cytometric analysis (FACS). In vitro, the THBA effect on chenodeoxycholic acid (CDCA)-induced inflammatory signaling in hepatocyte and cholangiocytes as well as lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma)-induced macrophage activation was analyzed. In contrast to Mdr2(-/-), DKO mice showed no features of sclerosing cholangitis. Sixty-seven percent of serum BAs in DKO mice were polyhydroxylated (mostly THBAs), whereas Mdr2(-/-) mice did not have these BAs. Compared with Mdr2(-/-), DKO animals were protected from hepatic inflammation/fibrosis. THBA feeding in Mdr2(-/-) mice improved liver injury. FACS analysis in DKO and Mdr2(-/-) THBA-fed mice showed changes of the hepatic immune cell profile towards an anti-inflammatory pattern. Early growth response 1 (EGR1) protein expression was reduced in DKO and in Mdr2(-/-) THBA-fed mice compared with Mdr2(-/-) control mice. In vitro, THBA-reduced CDCA induced EGR1 protein and mRNA expression of inflammatory markers in hepatocytes and cholangiocytes. LPS/IFN-gamma-induced macrophage activation was ameliorated by THBA. THBAs repress EGR1-related key pro-inflammatory pathways. Conclusion: THBA and their downstream targets may represent a potential treatment strategy for cholestatic liver diseases.

HPB : official journal of The international Hepato-Pancreato-Biliary Association 24(9), 1492-1500 (2022). doi:10.1016/j.hpb.2022.03.005, Published by Elsevier, [London]

BACKGROUND: Prior research suggested presurgical weight loss is associated with greater total weight loss, resulting in a more effective bariatric intervention. We aimed to assess whether preoperative weight loss is a predictor for total weight loss, and which patient factors are associated with successful weight loss.METHODS: All patients (N = 773) that underwent primary bariatric surgery between June 2017 and August 2019 were included in this single-center retrospective study. Outcome measures were preoperative weight loss (%preopWL) and total weight loss (%TWL) up to 1 year postoperatively. Patients were divided into 4 groups based on quartiles of %preopWL.RESULTS: Total weight loss after 1, 6, and 12 months for the upper quartile was 16.9%, 33.4%, and 37.8%, and for the lower quartile 11.8%, 28.9%, and 35.2%, respectively (p CONCLUSION: Higher preoperative weight loss is associated with persisting greater weight loss up to at least 12 months post-surgery. In order to optimize preoperative weight loss, we recommend extra preoperative support to younger and diabetic patients. We advise nutritional counseling and additional weight measurement in the week before surgery.

Backgrounds: COVID-19 related reduction of surgical procedures jeopardizes learning on the job of surgical residents. Many educators resorted to digital resources in the search for alternatives. However, these resources are often limited to the extent they offer resident-surgeon interaction like a joint surgical performance does. Here we present a roadmap of livestreaming surgical procedures, and evaluate how surgical livestreams on human cadavers address the unmet educational needs of surgical residents in our Dutch nationwide initiative. Methods: Technical and organizational feasibility, and definition of outcome deliverables for the livestream series and per livestream were essential in livestream development. Faculty selected interventions, lecture contents, and participant preparations. Appropriate location, technical setup, and support were imperative for a stable, high-quality stream with integrated interaction, while maintaining digital privacy. A survey was sent to livestream participants to evaluate each livestream, and allow for constant improvement during the broadcasting of the series. Only surveys which were completed by surgical residents were included in the analysis of this study. Results: Each livestream attracted 139–347 unique viewers and a total of 307 surveys were completed by participants (response rate of 23–38% per livestream). Sixty percent of surveys (n = 185) were completed by surgical residents. Livestreams were highly valued (appreciation 7.7 ± 1.1 and recommendation 8.6 ± 1.1), especially the live procedures combined with interaction and theoretical backgrounds. Criticized were technical difficulties and timing of the livestreams between 5 and 7 pm, which interfered with clinical duties. Conclusion: Livestreaming surgical procedures on human cadavers is a valid and valued solution to augment resident education. Digital privacy and a stable, high-quality interactive stream are essential, as are appropriate moderation and relevant lectures. While livestreaming cannot replace hands-on training in the operating room, it enables surgeon-resident interaction which is key in education—and missed in pre-recorded surgical procedures which are currently available online.

Genome-wide association studies in adults have identified variants in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) and mitochondrial amidoxime reducing component 1 (MTARC1) as protective against nonalcoholic fatty liver disease (NAFLD). We aimed to test their association with pediatric NAFLD liver histology and investigate their function using metabolomics. A total of 1450 children (729 with NAFLD, 399 with liver histology) were genotyped for rs72613567T>TA in HSD17B13, rs2642438G>A in MTARC1, and rs738409C>G in patatin-like phospholipase domain-containing protein 3 (PNPLA3). Genotype-histology associations were tested using ordinal regression. Untargeted hepatic proteomics and plasma lipidomics were performed in a subset of children. We found rs72613567T>TA in HSD17B13 to be associated with lower odds of NAFLD diagnosis (odds ratio, 0.7; 95% confidence interval, 0.6-0.9) and a lower grade of portal inflammation (p < 0.001). rs2642438G>A in MTARC1 was associated with a lower grade of hepatic steatosis (p = 0.02). Proteomics found reduced expression of HSD17B13 in carriers of the protective -TA allele. MTARC1 levels were unaffected by genotype. Both variants were associated with down-regulation of fibrogenic pathways. HSD17B13 perturbs plasma phosphatidylcholines and triglycerides. In silico modeling suggested p.Ala165Thr disrupts the stability and metal binding of MTARC1. Conclusion: Both HSD17B13 and MTARC1 variants are associated with less severe pediatric NAFLD. These results provide further evidence for shared genetic mechanisms between pediatric and adult NAFLD.

Background: Fatigue is often reported by colorectal cancer survivors and largely impacts their quality of life. Inflammation has been linked to fatigue mainly in patients with breast cancer. Therefore, we investigated how inflammation is longitudinally associated with fatigue in colorectal cancer survivors, up to 2 years posttreatment. Methods: A total of 257 patients from the ongoing Energy for life after ColoRectal cancer cohort study were included in the analysis. Plasma levels of IL6, IL8, IL10, TNFα, high-sensitivity C-reactive protein (hsCRP), and fatigue were measured at 6 weeks, 6, 12, and 24 months posttreatment. Fatigue was measured through the validated Checklist Individual Strength (CIS; total, 20–140), consisting of four subscales – subjective fatigue (8–56), motivation (4–28), physical activity (3–21), and concentration (5–35), and the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 fatigue subscale (0–100). Linear mixed-models were used to assess the confounder-adjusted longitudinal associations between inflammatory markers and overall fatigue along with the subscales. Results: Mean levels of CIS fatigue decreased from 62.9 at 6 weeks to 53.0 at 24 months. In general, levels of inflammatory markers also decreased over time. No statistically significant longitudinal associations were found between IL6, IL8, IL10, TNFα, and fatigue. Higher levels of hsCRP were associated with more CIS fatigue (β per SD 3.21, 95% confidence interval (CI), 1.42–5.01) and EORTC fatigue (β 2.41, 95% CI, 0.72–4.10). Conclusions: Increased levels of hsCRP are longitudinally associated with more posttreatment fatigue in colorectal cancer survivors. Impact: These findings suggest that low-grade inflammation may play a role in fatigue reported by colorectal cancer survivors up to 2 years posttreatment.

Introduction To assess the current approaches and perioperative treatments of laparoscopic right hemicolectomy (LRHC) and to highlight similarities and differences with international guidelines and scientific evidence, we conducted a survey for surgeons across the globe. Methods All digestive and colorectal surgeons registered with the database of the Research Institute against Digestive Cancer (IRCAD) were invited to take part in the survey via email and through the social media networks of IRCAD. Results There were a total of 440 respondents from 78 countries. Most surgeons worked in the European region (38.6%) followed by the Americas (34.1%), the Eastern Mediterranean region (13.0%), the South-East Asian region (5.9%), the Western Pacific region (4.8%), and Africa (3.2%) respectively. Over half of the respondents performed less than 25% of right hemicolectomies laparoscopically where 4 ports are usually used by 68% of the surgeons. The medial-to-lateral, vessel-first approach is the approach most commonly used (74.1%). The most common extraction site was through a midline incision (53%) and an abdominal drain tube is routinely used by 52% of the surgeons after surgery. A total of 68.6% of the responding surgeons perform the majority of the anastomoses extracorporeally. Finally, we found that the majority of responders (60.7%) routinely used mechanical bowel preparations prior to LRHC. Conclusion Regarding several topics related to LRHC care, a discrepancy was observed between the current medical practice and the recommendations from RCTs and international guidelines and significant regional differences were observed. Supplementary Information The online version contains supplementary material available at 10.1007/s00464-022-09044-w.

Objectives Cross-sectional studies show that endometriosis-related pain is associated with affect. Measuring these symptoms in real-time in a longitudinal perspective yields the ability to analyze the temporal relationship between variables. The aim was to evaluate the association between affect and abdominal pain, using the Experience Sampling Method (ESM) as a real-time, randomly repeated assessment. Methods Thirty-four endometriosis patients and 31 healthy subjects completed up to 10 real-time self-assessments concerning abdominal pain and affective symptoms during seven consecutive days. Results Endometriosis patients experienced more abdominal pain and negative affective symptoms, and scored lower on positive affect compared to healthy controls. A significant association was found between abdominal pain and both positive and negative affect in endometriosis patients. For healthy controls, less strong or non-significant associations were found. When looking at abdominal pain as a predictor for affect and vice versa, we found that only in endometriosis patients, pain was subsequently accompanied by negative affect, and positive affect may alleviate pain in these patients. Conclusions This study confirms a concurrent and temporal relationship between affect and abdominal pain in endometriosis patients and supports the use of real-time symptom assessment to interpret potential influencers of abdominal complaints in patients with endometriosis.

Journal of intensive care medicine 37(7), 970-978 (2022). doi:10.1177/08850666211052460, Published by Wiley-Blackwell, [Erscheinungsort nicht ermittelbar]