Serum-neuroproteins, near-infrared spectroscopy, and cognitive outcome after beach-chair shoulder surgery: Observational cohort study analyses.

BACKGROUND: Cerebral hypoxia may occur during surgery but currently used cerebral oxygenation saturation (rSO2) monitors remain controversial with respect to improving clinical outcome. Novel neuroprotein biomarkers are potentially released into systemic circulation and combined with near-infrared spectroscopy (NIRS) could clarify the presence of per-operative cerebral hypoxia. We investigated changes to serum-neuroprotein concentrations post-surgically, paired with NIRS and cognitive outcome, in patients operated in the beach chair position (BCP). METHODS: A prospective cohort in 28 shoulder surgery patients placed in the BCP. Blood samples were collected before induction of anaesthesia, and 2 hours and 3-5 days post-operatively. We analysed blood levels of biomarkers including tau and neurofilament light (NFL). We post hoc assessed the cross-wise relationship between biomarker levels and post-surgical changes in cognitive function and intraoperatively monitored rSO2 from NIRS. RESULTS: Serum-NFL decreased from 24.2 pg/mL to 21.5 (P = .02) 2 hours post-operatively, then increased to 27.7 pg/mL on day 3-5 (P = .03). Conversely, s-tau increased from 0.77 pg/mL to 0.98 (2 h), then decreased to 0.81 on day 3-5 (P = .08). In 14/28 patients, episodic rSO2 below 55% occurred, and the duration < 55% was correlated to change in s-tau (P < .05). The cognitive function z-score at 1 week and 3 mo. correlated to the change in tau (P = .01), but not to NFL. CONCLUSION: Some biomarkers were significantly changed with surgery in the beach chair position. The change was at some points associated to post-operative cognitive decline, and to intraoperative low rSO2. (237).

An Obturator Nerve Block does not Alleviate Postoperative Pain after Total Hip Arthroplasty: a Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: A substantial group of patients suffer from moderate to severe pain following elective total hip arthroplasty (THA). Due to the complex innervation of the hip, peripheral nerve block techniques can be challenging and are not widely used. Since the obturator nerve innervates both the anteromedial part of the joint capsule as well as intra-articular nociceptors, we hypothesized that an obturator nerve block (ONB) would decrease the opioid consumption after THA. METHODS: Sixty-two patients were randomized to receive ONB or placebo (PCB) after primary THA in spinal anesthesia. Primary outcome measure was opioid consumption during the first 12 postoperative hours. Secondary outcome measures included postoperative pain score, nausea score and ability to ambulate. RESULTS: Sixty patients were included in the analysis. Mean (SD) opioid consumption during the first 12 postoperative hours was 39.9 (22.3) mg peroral morphine equivalents (PME) in the ONB group and 40.5 (30.5) mg PME in the PCB group (p=0.93). No difference in level of pain or nausea was found between the groups. Paralysis of the hip adductor muscles in the ONB group reduced the control of the operated lower extremity compared with the PCB group (p=0.026). This did, however, not affect the subjects' ability to ambulate. CONCLUSIONS: A significant reduction in postoperative opioid consumption was not found for active versus PCB ONB after THA. TRIAL REGISTRATION NUMBER: NCT03064165 and 2017-000068-14.

Diet-Induced Abdominal Obesity, Metabolic Changes, and Atherosclerosis in Hypercholesterolemic Minipigs.

BACKGROUND: Obesity and metabolic syndrome (MetS) are major risk factors for atherosclerotic diseases; however, a causal link remains elusive. Animal models resembling human MetS and its complications, while important, are scarce. We aimed at developing a porcine model of human MetS. METHODS: Forty pigs with familial hypercholesterolemia were fed a high fat + fructose diet for 30 weeks. Metabolic assessments and subcutaneous fat biopsies were obtained at 18 and 30 weeks, and fat distribution was assessed by CT-scans. Postmortem, macrophage density, and phenotype in fat tissues were quantified along with atherosclerotic burden. RESULTS: During the experiment, we observed a >4-fold in body weight, a significant but small increase in fasting glucose (4.1 mmol/L), insulin (3.1 mU/L), triglycerides (0.5 mmol/L), and HDL cholesterol (2.6 mmol/L). Subcutaneous fat correlated with insulin resistance, but intra-abdominal fat correlated inversely with insulin resistance and LDL cholesterol. More inflammatory macrophages were found in visceral versus subcutaneous fat, and inflammation decreased in subcutaneous fat over time. CONCLUSIONS: MetS based on human criteria was not achieved. Surprisingly, visceral fat seemed part of a healthier metabolic and inflammatory profile. These results differ from human findings, and further research is needed to understand the relationship between obesity and MetS in porcine models.

In vitro differentiation of progenitor cells isolated from juvenile pig hearts - expression of relevant gene and protein markers.

OBJECTIVES: Heart failure is a significant cause of mortality worldwide, and most current therapies treat only its symptoms. The results of cardiac stem cell research suggest a promising treatment option for heart failure, but there is currently an unmet demand for better research models. We have therefore, for the first time, isolated, expanded and differentiated progenitor cells obtained from juvenile pig hearts to use as a platform for cardiac stem cell research. DESIGN: Progenitor cells were isolated from the left ventricles of porcine hearts using collagenase enzymatic digestion and Percoll®-gradient centrifugation. Cells were proliferated in Matrigel®-coated wells. Cell differentiation was initiated by applying 5-azacytidine and subsequently controlled by modifying the serum concentration. Western blotting and qPCR were used to determine protein and gene expression, respectively. RESULTS: Cardiac-specific genes, from the following proteins: troponin I-3, and myosin-heavy-chain 7 were stably expressed during proliferation and differentiation. Connexin-43 was upregulated and Actinin alfa 2 was downregulated during differentiation. The immature-cardiomyocyte marker GATA binding protein 4 was stably expressed but with a decrease in expression at day 4 of differentiation. Smooth muscle actin decreased in expression and Von Willebrand factor were stably expressed during differentiation. Smooth muscle protein expression was documented but no expression of cardiac-specific proteins after differentiation was found. CONCLUSION: The isolated progenitor cells had key cardiac-lineage gene expression characteristics but they did not express cardiac-specific proteins. Smooth muscle protein was expressed confirming commitment to the smooth muscle lineage.

Feasibility of day-case total hip arthroplasty: a single-centre observational study.

INTRODUCTION: Recent reports indicate that total hip arthroplasty (THA) can be further accelerated and might be managed as day-case. This could provide benefits to health care expenditure, lower patient risks and change patient satisfaction. We evaluated the feasibility, efficacy, safety and patient satisfaction of same-day (<12 hours) THA operation and discharge. METHODS: Consecutive patients were screened for eligibility (primary THA, ASA 1 or 2 physical status) and the presence of a support person to follow the patient for 48 hours postoperatively in an observational study. THA was managed as day-case (<12 hours) through patient selection, preoperative patient education programme, light spinal anaesthesia, low opioid usage, and early mobilisation. Efficacy and logistics were analysed and compared to current accelerated practice. Patient satisfaction was compared to existing fast-track THA and elective surgery cohorts. RESULTS: 29 consecutive patients were screened and 20 participated (69%). 17/20 patients (85%) were released on the day of surgery. There were no serious adverse events or complications, and no infections or readmission at 6-week follow-up. Patient overall satisfaction rating (1-5) was high (4.75), higher than in a 301-patient cohort (4.53) (THA and total knee arthroplasty) from the same centre (p = 0.23), and higher than in a national, elective surgery cohort (4.3) (p = 0.04). CONCLUSIONS: We report the feasibility of day-case THA. Safety, complications and overall patient acceptance were satisfactory. Light spinal anaesthesia facilitated quick transit through postanaesthesia care unit to early mobilisation. Support persons and patient education may play a part in high patient acceptance of day-case surgery.

Treatment with a human recombinant monoclonal IgG antibody against oxidized LDL in atherosclerosis-prone pigs reduces cathepsin S in coronary lesions.

BACKGROUND: Immunization with oxidized LDL (oxLDL) reduces atherosclerosis in rodents. We tested the hypothesis that treatment with a human recombinant monoclonal antibody against oxLDL will reduce the burden or composition of atherosclerotic lesions in hypercholesterolemic minipigs. METHODS AND RESULTS: Thirty-eight hypercholesterolemic minipigs with defective LDL receptors were injected with an oxLDL antibody or placebo weekly for 12weeks. An 18F-fluorodeoxyglucose positron emission tomography (FDG PET) scan (n=9) was performed before inclusion and after 3months of treatment. Blood samples were obtained prior to each injection. Following the last injection all animals were sacrificed, and the heart, aorta, and iliac arteries were removed. The left anterior descending coronary artery was sectioned at 5mm intervals for quantitative and qualitative assessments of atherosclerosis, including immunohistochemical phenotyping of macrophages using a pan-macrophage marker (CD68) and markers for putative pro-atherogenic (cathepsin S) and atheroprotective (CD163) macrophages. Aorta, right coronary artery, and left iliac artery were stained en face with Sudan IV and the amount of atherosclerosis quantified. There was no effect of treatment on plasma lipid profile, vascular FDG-PET signal or the amount of atherosclerosis in any of the examined arteries. However, immunostaining of coronary lesions revealed reduced cathepsin S positivity in the treated group compared with placebo (4.8% versus 8.2% of intima area, p=0.03) with no difference in CD68 or CD163 positivity. CONCLUSIONS: In hypercholesterolemic minipigs, treatment with a human recombinant monoclonal antibody against oxLDL reduced cathepsin S in coronary lesions without any effect on the burden of atherosclerosis or aortic FDG-PET signal.

Increased N-terminal CgA in circulation associated with cardiac reperfusion in pigs.

AIM: Acute myocardial infarction causes neurohumoral activation characterized by increased sympathetic activity. CgA is a protein released during sympathoadrenal stress from neuroendocrine tissue. Recently, increased CgA concentrations in circulation have been reported and suggested to be an independent predictor of mortality after acute myocardial infarction. MATERIALS & METHODS: Eighteen pigs underwent 1 h of regional myocardial ischemia followed by 3 h of reperfusion. Blood samples were collected every hour and plasma CgA was measured with two radioimmunoassays. RESULTS: We found a 30% increase in plasma N-terminal CgA 1 h after re-establishment of coronary blood supply. On the other hand, plasma pancreastatin did not change in response to ischemia or reperfusion but decreased during the entire experiment. CONCLUSION: Our results suggest a differentiated CgA response in myocardial reperfusion after local cardiac anoxia that may reflect tissue-specific post-translational processing and release.

The ICP-lowering effect of 10 degrees reverse Trendelenburg position during craniotomy is stable during a 10-minute period.

Recently we studied the effect of 10 degrees reverse Trendelenburg position on subdural pressure and cerebral perfusion pressure (CPP) during craniotomy. Within 1 minute we found a significant decrease in subdural pressure while CPP was unchanged. A longer time span, however, is necessary to exclude a temporary effect. In the present investigation we studied subdural pressure, CPP, and jugular bulb pressure (JBP) before and during a 10-minute period after change in position. Fifteen patients with supratentorial cerebral tumors were anesthetized with propofol/fentanyl in the supine position. Mean arterial blood pressure and JBP were measured invasively, and subdural pressure was measured after removal of the bone flap. End-tidal CO2, PaCO2, PaO2, heart rate, jugular venous oxygen saturation (SjO2), and arteriovenous oxygen difference (AVDO2) were also measured. Dural tension was estimated by the surgeon. The measurements were performed with the patients in a neutral position and during a 10-minute period after positioning the patient in a 10 degrees reverse Trendelenburg position. After 1 minute in the reverse Trendelenburg position, the mean value of subdural pressure decreased from 10.9 +/- 5.7 to 7.3 +/- 5.2 mm Hg (P<0.05) and remained unchanged for the following 9 minutes. Correspondingly, dural tension was lessened significantly. Jugular pressure and mean arterial blood pressure decreased significantly as well (P<0.05), but the CPP was unaffected. No significant changes in PaCO2, PaO2, end-tidal CO2, heart rate, SjO2, or AVDO2 were disclosed. During craniotomy 10 degrees reverse Trendelenburg position reduces subdural pressure and dural tension within 1 minute without reducing CPP. During the following 9 minutes the levels of subdural pressure and CPP are unchanged.