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BACKGROUND Pectus excavatum and pectus carinatum are the most common chest wall deformities. Although minimally invasive correction (MIPC) has become common practice, it remains associated with severe postoperative pain. Preoperative psychosocial factors such as anxiety and low self-esteem can increase postsurgical pain. Early detection of psychological symptoms, effective biopsychosocial perioperative management of patients and prevention of pain chronification using an enhanced recovery pathway (ERP) may improve outcomes. The incidence of the latter is poorly described in adolescents undergoing MIPC. OBJECTIVE To evaluate whether an ERP after surgery facilitated early recovery and to assess persistent postsurgical pain three months after surgery in pediatric patients undergoing MIPC using m-Health technology. METHODS A population-based cohort study was conducted with prospectively collected data from patients undergoing pectus surgery between June 2017 and December 2017. An ERP was initiated preoperatively and included patient education, eHealth-based psychological screening, multimodal preemptive analgesia, nausea prophylaxis as well as early Foley catheter removal and respiratory exercises. After hospital discharge, patients were assessed for up to ten weeks by evaluating pain and underwent rehabilitation using online diary and Bluetooth-connected telemonitoring devices. Retrospectively derived control patients in our hospital who were undergoing the same procedure without an ERP were matched by age (≤ 18 years). RESULTS Twenty-nine adolescents were enrolled using the developed ERP. Preemptive multimodal analgesia pain rating scores were low during hospital admission and were comparable between the groups. Optimal epidural placement occurred in 26 of the 29 participants (90%), hereby no motor block or Horner syndrome occurred. Bladder and epidural catheters were removed after 3.41 ± 1.50 and 5.76 ± 1.02 days, respectively. Low numeric pain rating scores (NRSs) and decreased incidence of nausea contributed to improved early rehabilitation. Telemonitoring at home was feasible in adolescents after hospital discharge despite adherence difficulties. Although pain scores at the final interview were low (0.81 ± 1.33), 9 out of 27 long-term follow up ERP patients (33%) still experienced frequent disturbing thoracic pain requiring analgesic administration, school absenteeism and multiple doctor (re)visits. CONCLUSIONS Allocating patients to the appropriate level of care preoperatively and immediately after surgery may improve long-term outcome variables. Using internet-based technologies and feasible, objective monitoring tools can help clinicians screen surgical patients for risk factors and initiate early treatment if necessary. Future research should focus on improving risk stratification and including a psychological assessment and evaluation of the effect of perioperative care pathways in children undergoing major surgery. CLINICALTRIAL ClinicalTrials.gov, NCT03100669, https://clinicaltrials.gov/ct2/show/NCT03100669

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease. The presence of portal hypertension has been demonstrated in NAFLD prior to development of inflammation or fibrosis, and is a result of extrahepatic and intrahepatic factors, principally driven by vascular dysfunction. An increased intrahepatic vascular resistance potentially contributes to progression of NAFLD via intralobular hypoxia. However, the exact mechanisms underlying vascular dysfunction in NAFLD remain unknown. This study investigates systemic hemodynamics and both aortic and intrahepatic vascular reactivity in a rat model of severe steatosis. Wistar rats were fed a methionine-choline-deficient diet, inducing steatosis, or control diet for 4 weeks. In vivo hemodynamic measurements, aortic contractility studies, and in situ liver perfusion experiments were performed. The mean arterial blood pressure was lower and portal blood pressure was higher in steatosis compared to controls. The maximal contraction force in aortic rings from steatotic rats was markedly reduced compared to controls. While blockade of nitric oxide (NO) production did not reveal any differences, cyclooxygenase (COX) blockade reduced aortic reactivity in both controls and steatosis, whereas effects were more pronounced in controls. Effects could be attributed to COX-2 iso-enzyme activity. In in situ liver perfusion experiments, exogenous NO donation or endogenous NO stimulation reduced the transhepatic pressure gradient (THPG), whereas NO synthase blockade increased the THPG only in steatosis, but not in controls. Alpha-1-adrenergic stimulation and endothelin-1 induced a significantly more pronounced increase in THPG in steatosis compared to controls. Our results demonstrate that severe steatosis, without inflammation or fibrosis, induces portal hypertension and signs of a hyperdynamic circulation, accompanied by extrahepatic arterial hyporeactivity and intrahepatic vascular hyperreactivity. The arterial hyporeactivity seems to be NO-independent, but appears to be mediated by specific COX-2-related mechanisms. Besides, the increased intrahepatic vascular resistance in steatosis appears not to be NO-related but rather to vasoconstrictor hyperreactivity.

Non-alcoholic fatty liver disease can progress to steatohepatitis and fibrosis, and is also associated with impaired liver regeneration. The pathophysiology remains elusive. We recently showed that severe steatosis is associated with an increase in portal pressure, suggesting liver flow impairment. The objective of this study is to directly assess total intrahepatic resistance and its potential functional and structural determinants in an in situ perfusion model. Male Wistar rats fed a control (n=30) or a methionine choline-deficient (MCD) diet (n=30) for 4 weeks were compared. Liver tissue and serum analysis, in vivo haemodynamic measurements, in situ perfusion experiments and vascular corrosion casts were performed. The MCD group showed severe steatosis without inflammation or fibrosis on histology. Serum levels and liver tissue gene expression of interleukin (IL)-6, tumour necrosis factor-alpha IL-1 beta and interferon-gamma, liver tissue myeloperoxidase activity and liver immunohistochemistry with anti-CD68 and anti-alpha smooth muscle actin were comparable between groups, excluding significant inflammation. Flow-pressure curves were significantly different between groups for all flows (slope values: 0.1636 +/- 0.0605 mm Hg/ml/min in controls vs 0.7270 +/- 0.0408 mm Hg/ml/min in MCD-fed rats, P