SurLym trial: study protocol for a multicentre pragmatic randomised controlled trial on the added value of reconstructive lymphatic surgery to decongestive lymphatic therapy for the treatment of lymphoedema.

INTRODUCTION: Lymphoedema is a chronic condition caused by lymphatic insufficiency. It leads to swelling of the limb/midline region and an increased risk of infection. Lymphoedema is often associated with mental and physical problems limiting quality of life. The first choice of treatment is a conservative treatment, consisting of exercises, skin care, lymph drainage and compression. Reconstructive lymphatic surgery is also often performed, that is, lymphovenous anastomoses, lymph node transfer or a combination. However, robust evidence on the effectiveness of reconstructive lymphatic surgery is missing. Therefore, the objective of this trial is to investigate the added value of reconstructive lymphatic surgery to the conservative treatment in patients with lymphoedema. METHODS AND ANALYSIS: A multicentre randomised controlled and pragmatic trial was started in March 2022 in three Belgian university hospitals. 90 patients with arm lymphoedema and 90 patients with leg lymphoedema will be included. All patients are randomised between conservative treatment alone (control group) or conservative treatment with reconstructive lymphatic surgery (intervention group). Assessments are performed at baseline and at 1, 3, 6, 12, 18, 24 and 36 months. The primary outcome is lymphoedema-specific quality of life at 18 months. Key secondary outcomes are limb volume and duration of wearing the compression garment at 18 months. The approach of reconstructive lymphatic surgery is based on presurgical investigations including clinical examination, lymphofluoroscopy, lymphoscintigraphy, lymph MRI or CT angiography (if needed). All patients receive conservative treatment during 36 months, which is applied by the patient's own physical therapist and by the patient self. From months 7 to 12, the hours a day of wearing the compression garment are gradually decreased. ETHICS AND DISSEMINATION: The study has been approved by the ethical committees of University Hospitals Leuven, Ghent University Hospital and CHU UCL Namur. Results will be disseminated via peer-reviewed journals and presentations. TRIAL REGISTRATION NUMBER: NCT05064176.

Multicentre retrospective analysis on pulmonary metastasectomy: an European perspective.

OBJECTIVES: To assess the current practice of pulmonary metastasectomy at 15 European Centres. Short- and long-term outcomes were analysed. METHODS: Retrospective analysis on patients ≥18 years who underwent curative-intent pulmonary metastasectomy (January 2010 to December 2018). Data were collected on a purpose-built database (REDCap). Exclusion criteria were: previous lung/extrapulmonary metastasectomy, pneumonectomy, non-curative intent and evidence of extrapulmonary recurrence at the time of lung surgery. RESULTS: A total of 1647 patients [mean age 59.5 (standard deviation; SD = 13.1) years; 56.8% males] were included. The most common primary tumour was colorectal adenocarcinoma. The mean disease-free interval was 3.4 (SD = 3.9) years. Relevant comorbidities were observed in 53.8% patients, with a higher prevalence of metabolic disorders (32.3%). Video-assisted thoracic surgery was the chosen approach in 54.9% cases. Wedge resections were the most common operation (67.1%). Lymph node dissection was carried out in 41.4% cases. The median number of resected lesions was 1 (interquartile range 25-75% = 1-2), ranging from 1 to 57. The mean size of the metastases was 18.2 (SD = 14.1) mm, with a mean negative resection margin of 8.9 (SD = 9.4) mm. A R0 resection of all lung metastases was achieved in 95.7% cases. Thirty-day postoperative morbidity was 14.5%, with the most frequent complication being respiratory failure (5.6%). Thirty-day mortality was 0.4%. Five-year overall survival and recurrence-free survival were 62.0% and 29.6%, respectively. CONCLUSIONS: Pulmonary metastasectomy is a low-risk procedure that provides satisfactory oncological outcomes and patient survival. Further research should aim at clarifying the many controversial aspects of its daily clinical practice.

Evaluation of Glucose Metrics in Adults with Type 1 Diabetes Switching to Insulin Glargine 300 U/mL: A Retrospective, Propensity-Score Matched Study.

Objectives: To study real-world effect of switching to Insulin Glargine 300 U/mL (Gla-300) on glucose metrics in people with type 1 diabetes. Methods: This retrospective secondary-use study compared 151 adults who switched to Gla-300 from first-generation long-acting insulins (Switchers) to 281 propensity-score matched controls (Non-switchers) who continued first-generation long-acting insulins. Primary endpoint was difference in time in range (TIR) evolution. A fictive "switching" date was assigned to Non-switchers to facilitate between-group comparisons. Results: In the period before switching, TIR decreased numerically for people in whom Gla-300 was eventually initiated (-0.05%/month [-0.16 to 0.07]), while it increased for matched controls (0.08%/month [0.02 to 0.015]; between-group difference P = 0.047). After Gla-300-initiation, Switchers had similar TIR increase compared to Non-switchers (P = 0.531). Switchers used higher basal dose than before switch (Δ0.012 U/[kg·d] [0.006 to 0.018]; P < 0.0001). Conclusion: In real-life, Gla-300 was typically initiated in people where TIR was decreasing, which was reversed after switch using slightly higher basal insulin dose. ClinicalTrials: ClinicalTrials.gov number NCT05109520.

Effectiveness of pain neuroscience education on somatosensory functioning after surgery for breast cancer: A double-blinded randomized controlled trial.

Pain is one of the most prevalent and long-term adverse effects described by people who have undergone breast cancer surgery. Non-helpful perceptions and thoughts about pain may contribute to the transition of acute to persistent pain. Adding educational interventions to the current physical therapy program in this population may help to improve or prevent persistent pain. Pain neuroscience education (PNE) is a type of educational intervention that addresses the experience of pain in a broader sense by explaining pain not only from a biomedical perspective, but also from a psychological and social perspective. A double-blinded randomized controlled trial (EduCan trial) investigated whether PNE, in addition to a standard physiotherapy program immediately after surgery for breast cancer, was more effective on somatosensory functioning in the short (4 months postoperatively) and long term (18 months postoperatively), than providing a biomedical explanation for pain. Somatosensory functioning was evaluated using a self-reported questionnaire as well as a comprehensive quantitative sensory testing evaluation. The findings of this study revealed that adding six sessions of PNE to a standard physical therapy program (n = 184) did not result in a significantly different course of somatosensory functioning up to 18 months postoperatively as compared to biomedical pain education. These findings provide an interesting basis for future research into who should receive PNE after surgery for breast cancer (e.g., patient profiling or phenotyping) and how we can tailor it to the individual to increase its effectiveness.

Incidence and risk factors of metachronous contralateral inguinal hernia development up to 25 years after unilateral inguinal hernia repair: a single-centre retrospective cohort study.

BACKGROUND: Patients undergoing unilateral inguinal hernia repair (IHR) are at risk of metachronous contralateral inguinal hernia (MCIH) development. We evaluated incidence and risk factors of MCIH development up to 25 years after unilateral IHR to determine possible indications for concomitant prophylactic surgery of the contralateral groin at the time of primary surgery. METHODS: Patients between 18 and 70 years of age undergoing elective unilateral IHR in the University Hospital of Leuven from 1995 to 1999 were studied retrospectively using the electronic health records and prospectively via phone calls. Study aims were MCIH incidence and risk factor determination. Kaplan-Meier curves were constructed and univariable and multivariable Cox regressions were performed. RESULTS: 758 patients were included (91% male, median age 53 years). Median follow-up time was 21.75 years. The incidence of operated MCIH after 5 years was 5.6%, after 15 years 16.1%, and after 25 years 24.7%. The incidence of both operated and non-operated MCIH after 5 years was 5.9%, after 15 years 16.7%, and after 25 years 29.0%. MCIH risk increased with older age and decreased in primary right-sided IHR and higher BMI at primary surgery. CONCLUSION: The overall incidence of MCIH after 25-year follow-up is 29.0%. Potential risk factors for the development of a MCIH are primary left-sided inguinal hernia repair, lower BMI, and older age. When considering prophylactic repair, we suggest a patient-specific approach taking into account these risk factors, the surgical approach and the risk factors for chronic postoperative inguinal pain.

Simultaneous Lung-abdominal Organ Procurement From Donation After Circulatory Death Donors Reduces Donor Hepatectomy Time.

BACKGROUND: Prolonged organ procurement time impairs the outcome of donation after circulatory death (DCD) and liver transplantation (LiT). Our transplant team developed a simultaneous, rather than sequential, lung-abdominal organ explantation strategy for DCD donation to prioritize liver procurement. We evaluated whether this change in strategy effectively reduced donor hepatectomy time (dHT), without affecting donor pneumonectomy time (dPT), and influenced LiT and lung transplantation outcome. METHODS: All lung-abdominal and abdominal-only transplant procedures between 2010 and 2020 were analyzed in this retrospective cohort study. Relationships were assessed between the year of transplant and dHT and dPT (univariate linear regression), 1-y patient and graft survival, primary graft dysfunction, and nonanastomotic biliary strictures (univariate logistic regression). RESULTS: Fifty-two lung-abdominal and 110 abdominal-only DCD procedures were analyzed. A significant decrease in dHT was noted in lung-abdominal (slope -1.14 [-2.14; -0.15], P = 0.026) but not in abdominal-only procedures; dPT did not increase. There were no significant associations between the year of transplant and nonanastomotic biliary strictures frequency, primary graft dysfunction incidence, 1-y patient, and graft survival. CONCLUSIONS: Simultaneous organ procurement in multiorgan lung-abdominal DCD procedures is feasible, and effectively shortened dHT without affecting lung transplantation outcome. No impact on LiT outcome was observed; however, larger multicenter studies are needed.

Appearance of the Bowel and Mesentery During Surgery Is Not Predictive of Postoperative Recurrence After Ileocecal Resection for Crohn's Disease: A Prospective Monocentric Study.

BACKGROUND: Very few risk factors for postoperative recurrence (POR) of Crohn's Disease (CD) after ileocecal resection have been identified. The aim of the present study was to verify the association between an a priori defined list of intraoperative macroscopic findings and POR. METHODS: This was a prospective observational study including patients undergoing primary ileocecal resection for CD. Four intraoperative factors were independently evaluated by 2 surgeons: length of resected ileum, mesentery thickness, presence of areas of serosal fat infiltration, or abnormal serosal vasodilation on normal bowel proximal to the resected bowel. The primary end point was early endoscopic POR at month 6 and defined as modified Rutgeerts score ≥i2b. Secondary end points were clinical and surgical recurrence. RESULTS: Between September 2020 and November 2022, 83 consecutive patients were included. Early endoscopic recurrence occurred in 45 of 76 patients (59.2%). Clinical and biochemical recurrence occurred in 17.3% (95% confidence interval, [CI], 10.4%-28.0%) and 14.6% of the patients after 12 months. The risk of developing endoscopic and clinical recurrence was 1.127 (95% CI, 0.448;2.834, P = .799) and 0.896 (95% CI, 0.324-2.478, P = .832) when serosal fat infiltration was observed, and 1.388 (95% CI, 0.554-3.476, P = .484), and 1.153 (95% CI, 0.417;3.187, P = .783) when abnormal serosal vasodilation was observed. Similarly, length of the resected bowel and mesentery thickness showed no association with POR. A subgroup analysis on patients who received no postoperative medical prophylaxis did not identify any risk factor for endoscopic POR. CONCLUSIONS: The macroscopic appearance of the bowel and associated mesentery during surgery does not seem to be predictive of POR after ileocecal resection for CD.

Prospective studies investigating risk factors for Crohn's disease recurrence after surgery are scarce. In a prospective cohort of 83 patients undergoing primary ileocecal resection, no association between few intraoperative macroscopic findings and postoperative endoscopic/clinical recurrence was observed.

The Effect of Continuous Liver Normothermic Machine Perfusion on the Severity of Histological Bile Duct Injury.

Static Cold Storage (SCS) injures the bile duct, while the effect of Normothermic Machine Perfusion (NMP) is unknown. In a sub-study of the COPE trial on liver NMP, we investigated the impact of preservation type on histological bile duct injury score (BDIS). Transplants with at least one bile duct biopsy, either at end of preservation or 1 h post-reperfusion, were considered. BDIS was determined by assessing peribiliary glands injury, stromal and mural loss, haemorrhage, and thrombosis. A bivariate linear model compared BDIS (estimate, CI) between groups. Sixty-five transplants and 85 biopsies were analysed. Twenty-three grafts were preserved with SCS and 42 with NMP, with comparable baseline characteristics except for a shorter cold ischemic time in NMP. The BDIS increased over time regardless of preservation type (p = 0.04). The BDIS estimate was higher in NMP [8.02 (7.40-8.65)] than in SCS [5.39 (4.52-6.26), p < 0.0001] regardless of time. One patient in each group developed ischemic cholangiopathy, with a BDIS of 6 for the NMP-preserved liver. In six other NMP grafts, BDIS ranged 7-12 without development of ischemic cholangiopathy. In conclusion, BDIS increases over time, and the higher BDIS in NMP did not increase ischemic cholangiopathy. Thus, BDIS may overestimate this risk after liver NMP.

Risk factors for forced expiratory volume in 1 s decline in European patients with cystic fibrosis: data from the European Cystic Fibrosis Society Patient Registry.

Aim: To examine the trajectory of forced expiratory volume in 1 s (FEV1) using data from the European Cystic Fibrosis Society patient registry (ECFPR) collected from 2008 to 2016, i.e. the era before highly effective modulator therapy (HEMT). We evaluated risk factors for FEV1 decline. Methods: The study population included patients with a confirmed diagnosis of cystic fibrosis recorded in the ECFPR (2008-2016). The evolution of FEV1 % predicted (%FEV1) with age, and the yearly change in %FEV1 were evaluated. Risk factors considered were cystic fibrosis transmembrane conductance regulator (-CFTR) mutation class, gender, age at diagnosis, neonatal screening, meconium ileus, sweat chloride concentration at diagnosis and country's income level. Results: We used 199 604 FEV1 recordings from 38 734 patients. The fastest decline was seen during puberty and in patients diagnosed before the age of 10 years. Males had a higher %FEV1, but a higher yearly %FEV1 loss between the ages of 15 and 25 years. We showed stabilisation and even improvement in %FEV1 over age in adults with a class III CFTR mutation, but a steady decline in patients homozygous for F508del or with both mutations of classes I/II. A faster decline in %FEV1 was found in patients from low-income countries compared to a similar %FEV1 evolution in patients from middle- and high-income countries. Conclusions: These longitudinal FEV1 data reflect the reality of cystic fibrosis across Europe in the era pre-HEMT, and can serve as baseline for comparison with the post-HEMT era. The similar evolution in middle- and high-income countries underlines opportunities for low-income countries.

Effect of anastomotic configuration on Crohn's disease recurrence after primary ileocolic resection: a comparative monocentric study of end-to-end versus side-to-side anastomosis.

There is ongoing debate whether the type of anastomosis following intestinal resection for Crohn's disease (CD) can impact on complications and postoperative recurrence. The aim of the present study is to describe the outcomes of side-to-side (S-S) vs end-to-end (E-E) anastomosis after ileocecal resection for CD. A retrospective comparative study was conducted in consecutive CD patients who underwent primary ileocecal resection between 2005 and 2013. All patients underwent colonoscopy 6 months postoperatively to assess endoscopic recurrence, defined as Rutgeerts' score (RS) ≥ i2. Surgical recurrence implied reoperation due to CD activity at the anastomotic site. Modified surgical recurrence was defined as the need for reoperation or balloon-dilation. Perioperative factors related to recurrence were evaluated. Of the 127 patients included, 51 (40.2%) received an E-E anastomosis. Median follow-up was longer in the E-E group (8.62 vs 13.68 years). Apart from the microscopic resection margins, patient, disease and surgical characteristics were similar between both groups. Anastomotic complications were comparable (S-S 5.3% vs E-E 5.8%, p = 1.00)0. Postoperatively, biologicals were used in 55.3% and 62.7% (p = 0.47) in S-S and E-E patients, respectively. Endoscopic recurrence did not differ between S-S and E-E patients (78.9 vs 72.9%, p = 0.37), with no significant difference in RS values between both groups (p = 0.87). Throughout follow-up, a higher surgical (p = 0.04) and modified surgical recurrence (p = 0.002) rate was observed in the E-E anastomosis group. Type of anastomosis was an independent risk factor for modified surgical recurrence. The type of anastomosis did not influence endoscopic recurrence and immediate postoperative disease complications. However, the wide diameter and the morphologic characteristic of the stapled S-S anastomosis resulted in a significant reduced risk for surgical and endoscopic reintervention on the long term.

The perioperative use of inhaled prostacyclins in cardiac surgery: a systematic review and meta-analysis.

PURPOSE: Perioperative pulmonary hypertension (PH) is an independent risk factor for morbidity and mortality in cardiac surgery. While inhaled prostacyclins (iPGI2s) are an established treatment of chronic PH, data on the efficacy of iPGI2s in perioperative PH are scarce. METHODS: We searched PubMed, Embase, the Web of Science, CENTRAL, and the grey literature from inception until April 2021. We included randomized controlled trials investigating the use of iPGI2s in adult and pediatric patients undergoing cardiac surgery with an increased risk of perioperative right ventricle failure. We assessed the efficacy and safety of iPGI2s compared with placebo and other inhaled or intravenous vasodilators with random-effect meta-analyses. The primary outcome was mean pulmonary artery pressure (MPAP). Secondary outcomes included other hemodynamic parameters and mortality. RESULTS: Thirteen studies were included, comprising 734 patients. Inhaled prostacyclins significantly decreased MPAP compared with placebo (standardized effect size, 0.46; 95% confidence interval [CI], 0.11 to 0.87; P = 0.01) and to intravenous vasodilators (1.26; 95% CI, 0.03 to 2.49; P = 0.045). Inhaled prostacyclins significantly improved the cardiac index compared with intravenous vasodilators (1.53; 95% CI, 0.50 to 2.57; P = 0.004). In contrast, mean arterial pressure was significantly lower in patients treated with iPGI2s vs placebo (-0.39; 95% CI, -0.62 to 0.16; P = 0.001), but higher than in patients treated with intravenous vasodilators (0.81; 95% CI, 0.29 to 1.33; P = 0.002). With respect to hemodynamics, iPGI2s had similar effects as other inhaled vasodilators. Mortality was not affected by iPGI2s. CONCLUSION: The results of this systematic review and meta-analysis show that iPGI2s improved pulmonary hemodynamics with similar efficacy as other inhaled vasodilators, but caused a significant small decrease in arterial pressure when compared with placebo, indicating spill-over into the systemic circulation. These effects did not affect clinical outcomes. STUDY REGISTRATION DATE: PROSPERO (CRD42021237991); registered 26 May 2021.

RéSUMé: OBJECTIF: L'hypertension pulmonaire (HTAP) périopératoire est un facteur de risque indépendant de morbidité et de mortalité en chirurgie cardiaque. Bien que l'inhalation de prostacyclines (iPGI2) constitue un traitement établi de l'HTAP chronique, les données sur l'efficacité de ce traitement en cas d'HTAP périopératoire sont rares. MéTHODE: Nous avons effectué des recherches dans les bases de données PubMed, Embase, Web of Science, CENTRAL et dans la littérature grise depuis leur création jusqu'en avril 2021. Nous avons inclus des études randomisées contrôlées portant sur l'utilisation de l'iPGI2 chez la patientèle adulte et pédiatrique bénéficiant d'une chirurgie cardiaque avec un risque accru d'insuffisance ventriculaire droite périopératoire. Nous avons évalué l'efficacité et l'innocuité des iPGI2 par rapport à un placebo et à d'autres vasodilatateurs inhalés ou intraveineux avec des méta-analyses à effets aléatoires. Le critère d'évaluation principal était la pression artérielle pulmonaire moyenne (PAPm). Les critères d'évaluation secondaires incluaient d'autres paramètres hémodynamiques et la mortalité. RéSULTATS: Treize études portant sur 734 patient·es ont été incluses. Les prostacyclines inhalées ont diminué de manière significative la PAPm par rapport au placebo (taille d'effet standardisée, 0,46; intervalle de confiance [IC] à 95 %, 0,11 à 0,87; P = 0,01) et aux vasodilatateurs intraveineux (1,26; IC 95 %, 0,03 à 2,49; P = 0,045). Les prostacyclines inhalées ont significativement amélioré l'index cardiaque par rapport aux vasodilatateurs intraveineux (1,53; IC 95 %, 0,50 à 2,57; P = 0,004). En revanche, la pression artérielle moyenne était significativement plus faible chez les patient·es traité·es par iPGI2 vs placebo (−0,39; IC 95 %, −0,62 à 0,16; P = 0,001), mais plus élevée que chez les personnes traitées par vasodilatateurs intraveineux (0,81; IC 95 %, 0,29 à 1,33; P = 0,002). En ce qui concerne l'hémodynamie, les iPGI2 ont eu des effets similaires à ceux des autres vasodilatateurs inhalés. La mortalité n'a pas été affectée par les iPGI2. CONCLUSION: Les résultats de cette revue systématique et méta-analyse montrent que les iPGI2 ont amélioré l'hémodynamie pulmonaire avec une efficacité similaire à celle des autres vasodilatateurs inhalés, mais ont entraîné une diminution légère mais significative de la pression artérielle par rapport au placebo, indiquant un débordement dans la circulation systémique. Ces effets n'ont pas affecté les résultats cliniques. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021237991); enregistrée le 26 mai 2021.

Returning to Work After Breast Cancer Surgery: A Randomised Controlled Trial on the Effect of Pain Neuroscience Education.

PURPOSE: The aim of this study was to investigate the effect of pain neuroscience education compared to biomedical pain education after breast cancer surgery on (1) work status, (2) time until work resumption, and (3) change in return-to-work expectations up to 18 months post-surgery. METHODS: Participants were randomly assigned to either pain neuroscience education (intervention group) or biomedical pain education (control group) in addition to a standard physical therapy program after surgery for breast cancer. The first four months following surgery, one to two physiotherapy sessions and three educational sessions were scheduled. After, two educational sessions and two physiotherapy sessions were held at six and eight months postoperatively. All outcomes were assessed at four, six, eight, 12 and 18 months postoperatively. RESULTS: At 12 months, in the intervention group, 71% of the women returned to work compared to 53% in the control group (18% points difference, 95%CI:-0.1 to 35;p = 0.07). At 18 months, the differences decreased to 9% points, 95%CI:-26 to 7;p = 0.35). Neither time until work resumption (p = 0.46) nor change in estimation of own ability to return to work up to 18 months postoperatively (p = 0.21) significantly differed between both groups. CONCLUSION: No significant differences were found regarding return to work outcomes between women receiving pain neuroscience education versus biomedical pain education after breast cancer surgery. Further research is warranted to explore the potential role of pain neuroscience education in return-to-work interventions following breast cancer surgery.

Erector spinae plane block for postoperative analgesia in robotically-assisted coronary artery bypass surgery: Results of a randomized placebo-controlled trial.

STUDY OBJECTIVE: To investigate if an erector spinae plane (ESP) block decreases postoperative opioid consumption, pain and postoperative nausea and vomiting in patients undergoing robotically-assisted minimally invasive direct coronary artery bypass surgery (RAMIDCAB). DESIGN: A single-center, double-blind, prospective, randomized, placebo-controlled trial. SETTING: Postoperative period; operating room, post-anesthesia care unit (PACU) and hospital ward in a university hospital. PATIENTS: Sixty-four patients undergoing RAMIDCAB surgery via left-sided mini-thoracotomy and enrolled in the institutional enhanced recovery after cardiac surgery program. INTERVENTIONS: At the end of surgery, patients received an ESP catheter at vertebra T5 under ultrasound guidance and were randomized to the administration of either ropivacaine 0.5% (loading dose of 30 ml and three additional doses of 20 ml each, interspersed with a 6 h interval) or normal saline 0.9% (with an identical administration scheme). In addition, patients received multimodal analgesia including acetaminophen, dexamethasone and patient-controlled analgesia with morphine. Following the final ESP bolus and before catheter removal, the position of the catheter was re-evaluated by ultrasound. Patients, investigators and medical personnel were blinded for the group allocation during the entire trial. MEASUREMENTS: Primary outcome was cumulative morphine consumption during the first 24 h after extubation. Secondary outcomes included location and severity of pain, presence/extent of sensory block, duration of postoperative ventilation and hospital length of stay. Safety outcomes comprised the incidence of adverse events. MAIN RESULTS: Median (IQR) 24-h morphine consumption was not different between the intervention- and control-groups, 67 mg (35-84) versus 71 mg (52-90) (p = 0.25), respectively. Likewise, no differences were detected in secondary and safety endpoints. CONCLUSIONS: Following RAMIDCAB surgery, adding an ESP block to a standard multimodal analgesia regimen did not reduce opioid consumption and pain scores.

Effect of a Combined Drug Approach on the Severity of Ischemia-Reperfusion Injury During Liver Transplant: A Randomized Clinical Trial.

Importance: In a porcine model of liver transplant, a combined drug approach that targeted the donor graft and graft recipient reduced ischemia-reperfusion injury, a major hurdle to the success of liver transplant. Objective: To assess the effect of a clinical form of a perioperative combined drug approach delivered immediately before implantation to the procured liver and to the liver recipient on the degree of ischemia-reperfusion injury. Design, Setting, and Participants: This unicentric, investigator-driven, open-label randomized clinical trial with 2 parallel arms was conducted in Belgium from September 2013 through February 2018, with 1-year follow-up. Adults wait-listed for a first solitary full-size liver transplant were screened for eligibility. Exclusion criteria were acute liver failure, kidney failure, contraindication to treatment, participation in another trial, refusal, technical issues, and death while awaiting transplant. Included patients were enrolled and randomized at the time of liver offer. Data were analyzed from May 20, 2019, to May 27, 2020. Interventions: Participants were randomized to a combined drug approach with standard of care (static cold storage) or standard of care only (control group). In the combined drug approach group, following static cold preservation, donor livers were infused with epoprostenol (ex situ, portal vein); recipients were given oral α-tocopherol and melatonin prior to anesthesia and intravenous antithrombin III, infliximab, apotransferrin, recombinant erythropoietin-ß, C1-inhibitor, and glutathione during the anhepatic and reperfusion phase. Main Outcomes and Measures: The primary outcome was the posttransplant peak serum aspartate aminotransferase (AST) level within the first 72 hours. Secondary end points were the frequencies of postreperfusion syndrome, ischemia-reperfusion injury score, early allograft dysfunction, surgical complications, ischemic cholangiopathy, acute kidney injury, acute cellular rejection, and graft and patient survival. Results: Of 93 randomized patients, 21 were excluded, resulting in 72 patients (36 per study arm) in the per protocol analysis (median recipient age, 60 years [IQR, 51.7-66.2 years]; 52 [72.2%] men). Peak AST serum levels were not different in the combined drug approach and control groups (geometric mean, 1262.9 U/L [95% CI, 946.3-1685.4 U/L] vs 1451.2 U/L [95% CI, 1087.4-1936.7 U/L]; geometric mean ratio, 0.87 [95% CI, 0.58-1.31]; P = .49) (to convert AST to µkat/L, multiply by 0.0167). There also were no significant differences in the secondary end points between the groups. Conclusions and Relevance: In this randomized clinical trial, the combined drug approach targeting the post-cold storage graft and the recipient did not decrease ischemic-reperfusion injury. The findings suggest that in addition to a downstream strategy that targets the preimplantation liver graft and the graft recipient, a clinically effective combined drug approach may need to include an upstream strategy that targets the donor graft during preservation. Dynamic preservation strategies may provide an appropriate delivery platform. Trial Registration: ClinicalTrials.gov Identifier: NCT02251041.

Lung Transplant Outcome From Selected Older Donors (≥70 Years) Equals Younger Donors (<70 Years): A Propensity-matched Analysis.

OBJECTIVE: To describe our experience with lung transplantation (LTx) from donors ≥70 years and compare short and long-term outcomes to a propensity-matched cohort of donors <70 years. BACKGROUND: Although extended-criteria donors have been widely used to enlarge the donor pool, the experience with LTx from older donors (≥70 years) remains limited. METHODS: All single-center bilateral LTx between 2010 and 2020 were retrospectively analyzed. Matching (1:1) was performed for the donor (type, sex, smoking history, x-ray abnormalities, partial pressure of oxygen/fraction of inspired oxygen ratio, and time on ventilator) and recipient characteristics (age, sex, LTx indication, perioperative extracorporeal life support, and cytomegalovirus mismatch). Primary graft dysfunction grade-3, 5-year patient, and chronic lung allograft dysfunction-free survival were analyzed. RESULTS: Out of 647 bilateral LTx, 69 were performed from donors ≥70 years. The mean age in the older donor cohort was 74 years (range: 70-84 years) versus 49 years (range: 12-69 years) in the matched younger group. No significant differences were observed in the length of ventilatory support, intensive care unit, or hospital stay. Primary graft dysfunction-3 was 26% in the older group versus 29% in younger donor recipients ( P = 0.85). Reintervention rate was comparable (29% vs 16%; P = 0.10). Follow-up bronchoscopy revealed no difference in bronchial anastomotic complications ( P = 1.00). Five-year patient and chronic lung allograft dysfunction-free survivals were 73.6% versus 73.1% ( P = 0.72) and 51.5% versus 59.2% ( P = 0.41), respectively. CONCLUSIONS: LTx from selected donors ≥70 years is feasible and safe, yielding comparable short and long-term outcomes in a propensity-matched analysis with younger donors (<70 years).

Efficacy of erector spinae plane block for minimally invasive mitral valve surgery: Results of a double-blind, prospective randomized placebo-controlled trial.

STUDY OBJECTIVE: To investigate if an erector spinae plane (ESP) block decreases postoperative opioid consumption, pain and postoperative nausea and vomiting in patients undergoing minimally invasive mitral valve surgery (MIMVS). DESIGN: A single-center, double-blind, prospective, randomized, placebo-controlled trial. SETTING: Postoperative period; operating room, post-anesthesia care unit (PACU) and hospital ward in a university hospital. PATIENTS: Seventy-two patients undergoing video-assisted thoracoscopic MIMVS via right-sided mini-thoracotomy and enrolled in the institutional enhanced recovery after cardiac surgery program. INTERVENTIONS: At the end of surgery, all patients received an ESP catheter at vertebra T5 under ultrasound guidance and were randomized to the administration of either ropivacaine 0.5% (loading of dose 30 ml and three additional doses of 20 ml with a 6 h interval) or normal saline 0.9% (with an identical administration scheme). In addition, patients received multimodal postoperative analgesia including dexamethasone, acetaminophen and patient-controlled intravenous analgesia with morphine. Following the final ESP bolus and before catheter removal, the position of the catheter was re-evaluated by ultrasound. Patients, investigators and medical personnel were blinded for the group allocation during the entire trial. MEASUREMENTS: Primary outcome was cumulative morphine consumption during the first 24 h after extubation. Secondary outcomes included severity of pain, presence/extent of sensory block, duration of postoperative ventilation and hospital length of stay. Safety outcomes comprised the incidence of adverse events. MAIN RESULTS: Median (IQR) 24-h morphine consumption was not different between the intervention- and control-group, 41 mg (30-55) versus 37 mg (29-50) (p = 0.70), respectively. Likewise, no differences were detected for secondary and safety endpoints. CONCLUSIONS: Following MIMVS, adding an ESP block to a standard multimodal analgesia regimen did not reduce opioid consumption and pain scores.

Effect of pain neuroscience education after breast cancer surgery on pain, physical, and emotional functioning: a double-blinded randomized controlled trial (EduCan trial).

ABSTRACT: Pain is one of the most common and long-lasting side effects reported by women surgically treated for breast cancer. Educational interventions may optimize the current physical therapy modalities for pain prevention or relief in this population. Pain neuroscience education (PNE) is an educational intervention that explains the pain experience not only from a biomedical perspective but also the psychological and social factors that contribute to it. Through a double-blinded randomized controlled trial (EduCan trial) it was investigated if PNE, in addition to the standard physiotherapy program immediately after breast cancer surgery, was more effective over the course of 18 months postoperatively than providing a biomedical explanation for pain. Primary outcome was the change in pain-related disability (Pain Disability Index, 0-70) over 12 months. Secondary outcomes included change in pain intensity, upper limb function, physical activity level, and emotional functioning over 4, 6, 8, 12, and 18 months postoperatively. Multivariate linear models for repeated (longitudinal) measures were used to compare changes. Preoperative and postoperative moderators of the change in pain-related disability were also explored. Of 184 participants randomized, the mean (SD) age in the PNE and biomedical education group was 55.4 (11.5) and 55.2 (11.4) years, respectively. The change in pain-related disability from baseline to 12 months postoperatively did not differ between the 2 groups (PNE 4.22 [95% confidence interval [CI]: 1.40-7.03], biomedical 5.53 [95% CI: 2.74-8.32], difference in change -1.31 [95% CI: -5.28 to 2.65], P = 0.516). Similar results were observed for all secondary outcomes. Future research should explore whether a more patient-tailored intervention would yield better results.

Effect of switching from intermittently scanned to real-time continuous glucose monitoring in adults with type 1 diabetes: 24-month results from the randomised ALERTT1 trial.

BACKGROUND: Comparing Continuous With Flash Glucose Monitoring In Adults With Type 1 Diabetes (ALERTT1) examined whether switching from first-generation intermittently scanned continuous glucose monitoring (isCGM) without alerts to real-time continuous glucose monitoring (rtCGM) with alert functionality offers additional benefits to adults with type 1 diabetes. The extension of the randomised ALERTT1 trial assessed the effect of switching from isCGM to rtCGM up to 24 months. METHODS: In this 6-month, double-arm, parallel-group, non-masked, randomised, controlled trial, done across six hospitals in Belgium, 254 adults aged 18 years or older with type 1 diabetes previously using isCGM were randomly assigned (1:1) to rtCGM with alerts (intervention; n=127) or isCGM without alerts (control; n=127). Upon completion of the 6-month trial, the control group switched to rtCGM (is-rtCGM group), and the intervention group continued rtCGM (rt-rtCGM group). The extension focused on within-group changes in time in range (TIR; 3·9-10·0 mmol/L; primary outcome), HbA1c, time in clinically significant hypoglycaemia (<3·0 mmol/L), and Hypoglycaemia Fear Survey worry (HFS-worry) score (all prespecified key secondary outcomes). Mean within-group change versus the start of rtCGM is reported, with a positive value referring to a lower value at start of rtCGM. This trial is registered at ClinicalTrials.gov (NCT03772600). FINDINGS: 119 participants were assigned to the is-rtCGM group of whom 112 (94%) completed the 24-month trial, and 123 participants were assigned to the rt-rtCGM group of whom 117 (95%) completed the 24-month trial. TIR increased from 51·8% (95% CI 49·1-54·5) at start of rtCGM (month 6) to 63·5% (60·7-66·3) at month 12 in the is-rtCGM group, and remained stable up to month 24 (change 11·7 percentage points [pp] [9·4-14·0; p<0·0001). In the rt-rtCGM group, TIR increased from 52·5% (95% CI 49·8-55·1) at start of rtCGM (month 0) to 63·0% (60·3-65·8) at month 12, also remaining stable up to month 24 (change 10·5 pp [8·2-12·8]; p<0·0001). HbA1c decreased from 7·4% (57 mmol/mol; month 6) to 6·9% (52 mmol/mol) at month 24 (change -0·54 pp [95% CI -0·64 to -0·44]; -5 mmol/mol [95% CI -6 to -4]; p<0·0001) in the is-rtCGM group, and from 7·4% (57 mmol/mol; month 0) to 7·0% (53 mmol/mol) at month 24 (change -0·43 pp [95% CI -0·53 to -0·33]; -4 mmol/mol [95% CI -5 to -3]; p<0·0001) in the rt-rtCGM group. The change in HFS-worry score was -2·67 (month 24 vs month 6; p=0·0008) in the is-rtCGM group and -5·17 points (month 24 vs month 0; p<0·0001) in the rt-rtCGM group. Time in clinically significant hypoglycaemia was unchanged in both groups after month 12. Severe hypoglycaemia decreased from 31·0 to 3·3 per 100 patient-years after switching to rtCGM. INTERPRETATION: Glycaemic control and hypoglycaemia worry improved significantly up to 24 months after switching from isCGM without alerts to rtCGM with alerts, supporting the use of rtCGM in the care of adults with type 1 diabetes. FUNDING: Dexcom.

Postoperative delirium and quality of life after transcatheter and surgical aortic valve replacement: A prospective observational study.

OBJECTIVE: In older patients, postoperative delirium is a frequently occurring complication after surgical aortic valve replacement, leading to an excess in postoperative morbidity and mortality. It remains controversial whether transcatheter aortic valve implantation and minimally invasive surgical aortic valve replacement can reduce the risk of postoperative delirium. This study aimed to compare the incidence of postoperative delirium after transcatheter aortic valve implantation and surgical aortic valve replacement and the impact on long-term outcomes. METHODS: Between September 2018 and January 2020, we conducted an observational, prospective cohort study in patients aged 70 years or more undergoing transcatheter aortic valve implantation or surgical aortic valve replacement. The primary end point was the incidence of in-hospital postoperative delirium during 5 postoperative days assessed with the Confusion Assessment Method. Secondary end points included perioperative inflammation, postoperative complications, health status (EuroQol 5-dimensional questionnaire 5 levels), and mortality up to 6 months. Transcatheter aortic valve implantation and surgical aortic valve replacement were compared using propensity weighting to account for important baseline differences (European System for Cardiac Operative Risk Evaluation II, age, and frailty). RESULTS: We included 250 patients with a mean (standard deviation) age of 80 (±5.8) years and a European System for Cardiac Operative Risk Evaluation score of 5 (±4.7). In the propensity-weighted analysis, those undergoing surgical aortic valve replacement (N = 166) had a higher incidence of postoperative delirium compared with transcatheter aortic valve implantation (N = 84) (51% vs 15%: P < .0001). Furthermore, patients undergoing surgical aortic valve replacement experienced more inflammation, a greater depth of anesthesia, and more intraoperative hypotension. After surgical aortic valve replacement, 41% of patients experienced an improved health status compared with 12% after transcatheter aortic valve implantation (P < .0001). No outcome differences were noted within the surgical aortic valve replacement groups. CONCLUSIONS: Transcatheter aortic valve implantation is associated with a lower risk for postoperative delirium. Nevertheless, patients undergoing surgical aortic valve replacement experience the greatest improvement in quality of life. Heart teams should consider these outcomes in shared decision-making in the choice of transcatheter aortic valve implantation or surgical aortic valve replacement.

The Impact of Baseline User Characteristics on the Benefits of Real-Time Versus Intermittently Scanned Continuous Glucose Monitoring in Adults With Type 1 Diabetes: Moderator Analyses of the ALERTT1 Trial.

BACKGROUND: ALERTT1 showed that switching from intermittently scanned continuous glucose monitoring (isCGM) without alerts to real-time CGM (rtCGM) with alert functionality improved time in range (TIR; 70-180 mg/dL), glycated hemoglobin (HbA1c), time <54 mg/dL, and Hypoglycemia Fear Survey version II worry subscale (HFS-worry) score after six months in adults with type 1 diabetes (T1D). Moderator analyses aimed to identify certain subgroups that would benefit more from switching to rtCGM than others. METHODS: Post hoc analyses of ALERTT1 evaluated the impact of 14 baseline characteristics on the difference (delta) in mean TIR, HbA1c, time <54 mg/dL, and HFS-worry score at six months between rtCGM and isCGM. Therefore, the delta was allowed to depend on each of these variables by including interactions in the moderator analysis model. Analyses were performed separately for each variable; variables with P < .10 in the univariable analysis were combined into a single model. RESULTS: Univariable analyses showed no dependency of delta TIR, HbA1c, or time <54 mg/dL on variables other than CGM type. Only delta HFS-worry score depended on baseline HbA1c (P = .0059), indicating less worries with rtCGM in people with baseline HbA1c <6.5% or ≥8%. Given P < .10 for dependency of delta TIR on insulin therapy type (favoring multiple daily injections), baseline HbA1c, and baseline TIR, these variables were combined into a multivariable analysis; interactions were not statistically significant. CONCLUSIONS: Except for HFS-worry score, no interactions between 14 baseline characteristics and the six-month intervention effect of rtCGM on TIR, HbA1c, or time <54 mg/dL were observed, supporting the conclusion of ALERTT1 that switching from isCGM without alerts to rtCGM with alert functionality is beneficial for a wide range of people with T1D.