Autoantibodies Targeting Nephrin in Podocytopathies.

BACKGROUND: Minimal change disease and primary focal segmental glomerulosclerosis in adults, along with idiopathic nephrotic syndrome in children, are immune-mediated podocytopathies that lead to nephrotic syndrome. Autoantibodies targeting nephrin have been found in patients with minimal change disease, but their clinical and pathophysiological roles are unclear. METHODS: We conducted a multicenter study to analyze antinephrin autoantibodies in adults with glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, IgA nephropathy, antineutrophil cytoplasmic antibody-associated glomerulonephritis, and lupus nephritis, as well as in children with idiopathic nephrotic syndrome and in controls. We also created an experimental mouse model through active immunization with recombinant murine nephrin. RESULTS: The study included 539 patients (357 adults and 182 children) and 117 controls. Among the adults, antinephrin autoantibodies were found in 46 of the 105 patients (44%) with minimal change disease, 7 of 74 (9%) with primary focal segmental glomerulosclerosis, and only in rare cases among the patients with other conditions. Of the 182 children with idiopathic nephrotic syndrome, 94 (52%) had detectable antinephrin autoantibodies. In the subgroup of patients with active minimal change disease or idiopathic nephrotic syndrome who were not receiving immunosuppressive treatment, the prevalence of antinephrin autoantibodies was as high as 69% and 90%, respectively. At study inclusion and during follow-up, antinephrin autoantibody levels were correlated with disease activity. Experimental immunization induced a nephrotic syndrome, a minimal change disease-like phenotype, IgG localization to the podocyte slit diaphragm, nephrin phosphorylation, and severe cytoskeletal changes in mice. CONCLUSIONS: In this study, circulating antinephrin autoantibodies were common in patients with minimal change disease or idiopathic nephrotic syndrome and appeared to be markers of disease activity. Their binding at the slit diaphragm induced podocyte dysfunction and nephrotic syndrome, which highlights their pathophysiological significance. (Funded by Deutsche Forschungsgemeinschaft and others.).

Goal-directed colloid versus crystalloid therapy and microcirculatory blood flow following ischemia/reperfusion.

OBJECTIVE: Ischemia/reperfusion can impair microcirculatory blood flow. It remains unknown whether colloids are superior to crystalloids for restoration of microcirculatory blood flow during ischemia/reperfusion injury. We tested the hypothesis that goal-directed colloid - compared to crystalloid - therapy improves small intestinal, renal, and hepatic microcirculatory blood flow in pigs with ischemia/reperfusion injury. METHODS: This was a randomized trial in 32 pigs. We induced ischemia/reperfusion by supra-celiac aortic-cross-clamping. Pigs were randomized to receive either goal-directed isooncotic hydroxyethyl-starch colloid or balanced isotonic crystalloid therapy. Microcirculatory blood flow was measured using Laser-Speckle-Contrast-Imaging. The primary outcome was small intestinal, renal, and hepatic microcirculatory blood flow 4.5 h after ischemia/reperfusion. Secondary outcomes included small intestinal, renal, and hepatic histopathological damage, macrohemodynamic and metabolic variables, as well as specific biomarkers of tissue injury, renal, and hepatic function and injury, and endothelial barrier function. RESULTS: Small intestinal microcirculatory blood flow was higher in pigs assigned to isooncotic hydroxyethyl-starch colloid therapy than in pigs assigned to balanced isotonic crystalloid therapy (768.7 (677.2-860.1) vs. 595.6 (496.3-694.8) arbitrary units, p = .007). There were no important differences in renal (509.7 (427.2-592.1) vs. 442.1 (361.2-523.0) arbitrary units, p = .286) and hepatic (604.7 (507.7-701.8) vs. 548.7 (444.0-653.3) arbitrary units, p = .376) microcirculatory blood flow between groups. Pigs assigned to colloid - compared to crystalloid - therapy also had less small intestinal, but not renal and hepatic, histopathological damage. CONCLUSIONS: Goal-directed isooncotic hydroxyethyl-starch colloid - compared to balanced isotonic crystalloid - therapy improved small intestinal, but not renal and hepatic, microcirculatory blood flow in pigs with ischemia/reperfusion injury. Whether colloid therapy improves small intestinal microcirculatory blood flow in patients with ischemia/reperfusion needs to be investigated in clinical trials.

Anterior Vertebral Body Tethering for Skeletally Immature Patients with AIS: Indication for Spinal Fusion at Skeletal Maturity Is Not Obviated in 60% of Cases.

The role of anterior vertebral body tethering (aVBT) in obviating the need for spinal fusion in patients with AIS remains unclear, and a large amount of variation exists in the data among different studies. The present study aims to investigate and analyze what factors have a potential influence on aVBT outcome. Skeletally immature patients with AIS who underwent aVBT for scoliosis correction were followed up until skeletal maturity. The mean age at the time of surgery was 13.4 ± 1.1, and the mean follow-up time was 2.5 ± 0.5 years. The Cobb angle of the main curve was 46.6 ± 9° at the time of surgery and was significantly corrected to 17.7 ± 10.4° (p < 0.001) immediately postoperatively. A significant loss of correction was observed during the latest follow-up (Cobb angle 33.8 ± 18.7°; p < 0.001). An indication for spinal fusion at skeletal maturity was not obviated in 60% of the patients. The factors identified as having an influence on the outcome were preoperative bone age and the magnitude of the major curve. Patients with advanced bone age and larger curves were more likely to reach an indication for spinal fusion at skeletal maturity. In conclusion, no general recommendation for aVBT can be made for AIS patients. The method can be discussed as a treatment option in skeletally very immature preadolescent patients (Sanders Stadium ≤ 2) with a moderate Cobb angle (≤50°) who failed previous brace therapy.

Impact of COVID-19 on Sedation Requirements during Veno-Venous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome.

COVID-19-associated ARDS (C-ARDS) is mentioned to express higher analgosedation needs, in comparison to ARDS of other etiologies. The objective of this monocentric retrospective cohort study was to compare the analgosedation needs between C-ARDS and non-COVID-19 ARDS (non-C-ARDS) on veno-venous extracorporeal membrane oxygenation (VV-ECMO). Data were collected from the electronic medical records of all adult patients treated with C-ARDS in our Department of Intensive Care Medicine between March 2020 and April 2022. The control group included patients treated with non-C-ARDS between the years 2009 and 2020. A sedation sum score was created in order to describe the overall analgosedation needs. A total of 115 (31.5%) patients with C-ARDS and 250 (68.5%) with non-C-ARDS requiring VV-ECMO therapy were included in the study. The sedation sum score was significantly higher in the C-ARDS group (p < 0.001). COVID-19 was significantly associated with analgosedation in the univariable analysis. By contrast, the multivariable model did not show a significant association between COVID-19 and the sum score. The year of VV-ECMO support, BMI, SAPS II and prone positioning were significantly associated with sedation needs. The potential impact of COVID-19 remains unclear, and further studies are warranted in order to evaluate specific disease characteristics linked with analgesia and sedation.

Effect of thoracic epidural anesthesia on postoperative outcome in major liver surgery: a retrospective cohort study.

PURPOSE: Postoperative complications after major liver surgery are common. Thoracic epidural anesthesia may provide beneficial effects on postoperative outcome. We strove to compare postoperative outcomes in major liver surgery patients with and without thoracic epidural anesthesia. METHODS: This was a retrospective cohort study in a single university medical center. Patients undergoing elective major liver surgery between April 2012 and December 2016 were eligible for inclusion. We divided patients into two groups according to whether or not they had thoracic epidural anesthesia for major liver surgery. The primary outcome was postoperative hospital length of stay, i.e., from day of surgery until hospital discharge. Secondary outcomes included 30-day postoperative mortality and major postoperative complications. Additionally, we investigated the effect of thoracic epidural anesthesia on perioperative analgesia doses and the safety of thoracic epidural anesthesia. RESULTS: Of 328 patients included in this study, 177 (54.3%) received thoracic epidural anesthesia. There were no clinically important differences in postoperative hospital length of stay (11.0 [7.00-17.0] vs. 9.00 [7.00-14.0] days, p = 0.316, primary outcome), death (0.0 vs. 2.7%, p = 0.995), or the incidence of postoperative renal failure (0.6 vs. 0.0%, p = 0.99), sepsis (0.0 vs. 1.3%, p = 0.21), or pulmonary embolism (0.6 vs. 1.4%, p = 0.59) between patients with or without thoracic epidural anesthesia. Perioperative analgesia doses - including the intraoperative sufentanil dose (0.228 [0.170-0.332] vs. 0.405 [0.315-0.565] µg·kg-1·h-1, p < 0.0001) - were lower in patients with thoracic epidural anesthesia. No major thoracic epidural anesthesia-associated infections or bleedings occurred. CONCLUSION: This retrospective analysis suggests that thoracic epidural anesthesia does not reduce postoperative hospital length of stay in patients undergoing major liver surgery - but it may reduce perioperative analgesia doses. Thoracic epidural anesthesia was safe in this cohort of patients undergoing major liver surgery. These findings need to be confirmed in robust clinical trials.

Subthalamic and nigral neurons are differentially modulated during parkinsonian gait.

The parkinsonian gait disorder and freezing of gait are therapeutically demanding symptoms with considerable impact on quality of life. The aim of this study was to assess the role of subthalamic and nigral neurons in the parkinsonian gait control using intraoperative microelectrode recordings of basal ganglia neurons during a supine stepping task. Twelve male patients (56 ± 7 years) suffering from moderate idiopathic Parkinson's disease (disease duration 10 ± 3 years, Hoehn and Yahr stage 2), undergoing awake neurosurgery for deep brain stimulation, participated in the study. After 10 s resting, stepping at self-paced speed for 35 s was followed by short intervals of stepping in response to random 'start' and 'stop' cues. Single- and multi-unit activity was analysed offline in relation to different aspects of the stepping task (attentional 'start' and 'stop' cues, heel strikes, stepping irregularities) in terms of firing frequency, firing pattern and oscillatory activity. Subthalamic nucleus and substantia nigra neurons responded to different aspects of the stepping task. Of the subthalamic nucleus neurons, 24% exhibited movement-related activity modulation as an increase of the firing rate, suggesting a predominant role of the subthalamic nucleus in motor aspects of the task, while 8% of subthalamic nucleus neurons showed a modulation in response to the attentional cues. In contrast, responsive substantia nigra neurons showed activity changes exclusively associated with attentional aspects of the stepping task (15%). The firing pattern of subthalamic nucleus neurons revealed gait-related firing regularization and a drop of beta oscillations during the stepping performance. During freezing episodes instead, there was a rise of beta oscillatory activity. This study shows for the first time specific, task-related subthalamic nucleus and substantia nigra single-unit activity changes during gait-like movements in humans with differential roles in motor and attentional control of gait. The emergence of perturbed firing patterns in the subthalamic nucleus indicates a disrupted information transfer within the gait network, resulting in freezing of gait.

Validation of three nociception indices to predict immediate postoperative pain before emergence from general anaesthesia: a prospective double-blind, observational study.

BACKGROUND: Nociception monitoring devices are designed to estimate nociception during general anaesthesia. We evaluated the predictive accuracy of heart rate and three nociception indices to predict postoperative pain before emergence from general anaesthesia. METHODS: In patients undergoing trauma or orthopaedic surgery, HR, Surgical Pleth Index® (SPI), Pupillary Pain Index® (PPI), and Nociception Level® (NOL) were simultaneously recorded for 5 min after the end of surgery but before return of consciousness. After admission to the recovery room, pain scores were assessed regularly for 2 h. HR, SPI, PPI, and NOL were analysed for their predictive accuracy of postoperative pain and opioid consumption with assessment of area under the receiver operating characteristic (AUC) curves, Spearman rank-correlation coefficient, and regression modelling. RESULTS: Data for 60 subjects were analysed. The AUC (95% confidence interval [95% CI]) of the predictive accuracy for moderate-to-severe postoperative pain differed between nociception indices (HR=0.46 [0.29-0.64], P=0.671; SPI=0.46 [0.31-0.61], P=0.621; PPI=0.52 [0.36-0.68], P=0.770; NOL=0.66 [0.51-0.81], P=0.038). In a multivariable logistic regression model, a higher predictive accuracy was found for a multivariable predictor combining NOL values with ASA physical status and information about use of regional anaesthesia (AUC=0.83 [0.72-0.94], P<0.001). CONCLUSIONS: Heart rate, Surgical Pleth Index, Pupillary Pain Index, and Nociception Level measured before emergence from general anaesthesia do not yet have sufficient diagnostic accuracy for prediction of postoperative pain. CLINICAL TRIAL REGISTRATION: NCT05063227.

The impact of nitroglycerine and volume on gastric tube microperfusion assessed by indocyanine green fluorescence imaging.

The influence of hypervolemia and intraoperative administration of nitroglycerine on gastric tube microperfusion remains unclear The present study aimed to investigate the impact of different hemodynamic settings on gastric tube microperfusion quantified by fluorescence imaging with Indocyanine green (ICG-FI) as a promising tool for perfusion evaluation. Three groups with seven pigs each were formed using noradrenaline, nitroglycerin, and hypervolemia for hemodynamic management, respectively. ICG-FI, hemodynamic parameters, and transit-time flow measurement (TTFM) in the right gastroepiploic artery were continuously assessed. Fluorescent microspheres (FM) were administered, and the partial pressure of tissue oxygen was quantified. The administration of nitroglycerine and hypervolemia were both associated with significantly impaired microperfusion compared to the noradrenaline group quantified by ICG-FI. Even the most minor differences in microperfusion could be sufficiently predicted which, however, could not be represented by the mean arterial pressure measurement. Histopathological findings supported these results with a higher degree of epithelial damage in areas with impaired perfusion. The values measured by ICG-FI significantly correlated with the FM measurement. Using tissue oxygenation and TTFM for perfusion measurement, changes in microperfusion could not be comprehended. Our results support current clinical practice with restrictive volume and catecholamine administration in major surgery. Hypervolemia and continuous administration of nitroglycerine should be avoided.

The impact of spinal anaesthesia on perioperative opioid consumption, postoperative pain and oncological outcome in radical retropubic prostatectomy-a retrospective before-and-after effectiveness study.

BACKGROUND: Spinal anaesthesia preceding general anaesthesia has been conducted for open radical retropubic prostatectomy (RRP) to decrease immediate postoperative pain for many years. Nevertheless, the effectiveness of spinal anaesthesia to reduce postoperative opioid requirements remains unknown. The aim of the present study was to determine the effect of spinal anaesthesia preceding general anaesthesia on opioid requirements, postoperative pain and biochemical cancer-free survival. METHODS: This before-and-after effectiveness study investigated effects of two different anaesthesia techniques in 636 patients with RRP. Three hundred eighteen consecutive patients in the SPA group (spinal anaesthesia preceding general anaesthesia) were compared with 318 patients in the GA group (general anaesthesia alone). The primary endpoint of the study was opioid consumption in the post-anaesthesia care unit. Secondary endpoints were intraoperative opioid consumption, postoperative pain, postoperative recovery time, the length of hospital-stay, persistence of pain 1 year after surgery and cancer-free survival. Differences between the groups were analysed by a two-sided t-test, χ2-test, Fisher's exact test and Mann-Whitney U test and the influence of possible confounders on opioid consumption with a general linear model. Cancer-free survival was determined by Kaplan-Meier curves and group differences by log-rank tests and multivariable Cox regression analyses. RESULTS: The total amount of morphine equivalent administered postoperatively was 7.5 [6.9; 8.1] mg in the SPA group and 6.0 [5.5; 6.5] mg in the GA group (mean [95% CI], p < 0.001). The amount of intraoperative sufentanil was 56.9 [55.1; 58.7] µg in the SPA group and 84.5 [82.5; 86.5] µg in the GA group (mean [95% CI], p < 0.001). There was no difference found in the postoperative pain level, length of hospital-stay and pain level 1 year after surgery. Biochemical cancer-free survival was highly related to TNM stage (p < 0.001, pT3 vs. pT2 hazard ratio 5.4 [95%CI 3.3; 9.2]) but not to the type of anaesthesia (p = 0.29). CONCLUSIONS: Spinal anaesthesia preceding general anaesthesia for RRP is associated with increased postoperative opioid consumption compared to general anaesthesia alone. Postoperative pain level and the oncological outcome are not affected by the adjunctive use of spinal anaesthesia. Thus, the addition of spinal anaesthesia to general anaesthesia has no advantage in RRP. TRIAL REGISTRATION: ClinicalTrial.gov, NCT03565705.

Ablation of Outflow Tract Arrhythmias in Patients With and Without Structural Heart Disease-A Comparative Analysis.

Introduction: Catheter ablation of ventricular arrhythmias emerging from the ventricular outflow tracts and adjacent structures is very effective and considered almost curative in patients without structural heart disease (SHD). Outcomes of patients with SHD undergoing ablation of outflow tract arrhythmias are not known. Methods: Consecutive patients (2019-2021) undergoing catheter ablation of ventricular arrhythmias in a single high-volume center were retrospectively analyzed. Patients with ablation of outflow tract arrhythmias were identified and divided in individuals with and without SHD. Procedural parameters and acute outcome were compared. Results: We identified 215 patients with outflow tract arrhythmias (35.3% female, mean age 58.3 ± 16.0 years). Of those, 93 (43.3%) had SHD. Patients with SHD and outflow tract arrhythmias were older (65.0 ± 12.8 vs. 53.3 ± 16.3 years; p < 0.001), more often male (82.8 vs. 50.0%; p < 0.001) and had more comorbidities than patients without SHD (arterial hypertension: 62.4 vs. 34.4%, p < 0.001; diabetes: 22.6 vs. 8.2%, p = 0.005; chronic lung disease: 20.4 vs. 7.4%, p = 0.007). Outflow tract arrhythmias in patients with SHD had their origin more often in the left ventricle (68.8 vs. 53.3%, p = 0.025). The acute success rate was similar in both patient groups (93.4 vs. 94.2%, p = 0.781). Patients with SHD were discharged later {median length of hospital stay with SHD 5 [6 (interquartile range)] days, without SHD 2 [4] days, p < 0.001}. Periprocedural complications were numerically more frequent in patients with SHD [with SHD 12 (12.9%), without SHD 8 (6.6%), p = 0.154]. Conclusion: Outflow tract arrhythmia ablation has a high success rate irrespective of the presence of SHD. Longer hospital stay and potentially a higher risk of periprocedural complications should be considered when discussing this treatment option with patients.

Effects of fluids vs. vasopressors on spinal cord microperfusion in hemorrhagic shock induced ischemia/reperfusion.

OBJECTIVE: Spinal cord injury induced by ischemia/reperfusion is a devastating complication of aortic repair. Despite developments for prevention and treatment of spinal cord injury, incidence is still considerably high majorly impacting patient outcome. Microcirculation is paramount for tissue perfusion and oxygen supply and often dissociated from macrohemodynamic parameters used to guide resuscitation. Effects of fluids vs. vasopressors in the setting of hemodynamic resuscitation on spinal cord microperfusion are unknown. Aim of this study was to compare the effects of vasopressor and fluid resuscitation on spinal cord microperfusion in a translational acute pig model of hemorrhagic shock induced ischemia/reperfusion injury. METHODS: We designed this study as prospective randomized explorative large animal study. We induced hemorrhagic shock in 20 pigs as a model of global ischemia/reperfusion injury. We randomized animals to receive either fluid or vasopressor resuscitation. We measured spinal cord microperfusion using fluorescent microspheres as well as laser-Doppler probes. We monitored and analyzed macrohemodynamic parameters and cerebrospinal fluid pressure. RESULTS: Spinal cord microperfusion decreased following hemorrhagic shock induced ischemia/reperfusion injury. Both fluids and vasopressors sufficiently restored spinal cord microperfusion. There were no important changes between groups (percentage changes compared to baseline: fluids 14.0 (0.31-27.6) vs. vasopressors 24.3 (8.12-40.4), p = .340). However, cerebrospinal fluid pressure was higher in animals receiving fluid resuscitation (percentage changes compared to baseline: fluids 27.7 (12.6-42.8) vs. vasopressors -5.56 ((-19.8)-8.72), p = .003). Microcirculatory resuscitation was in line with improvements of macrohemodynamic parameters. CONCLUSIONS: Both, fluids and vasopressors, equally restored spinal cord microperfusion in a porcine acute model of hemorrhagic shock induced ischemia/reperfusion injury. However, significant differences in cerebrospinal fluid pressure following resuscitation were present. Future studies should evaluate these effects in perfusion disruption induced ischemia/reperfusion conditions of microcirculatory deterioration.

Subthalamic Deep Brain Stimulation Lead Asymmetry Impacts the Parkinsonian Gait Disorder.

Background: The preferable position of Deep Brain Stimulation (DBS) electrodes is proposed to be located in the dorsolateral subthalamic nucleus (STN) to improve general motor performance. The optimal DBS electrode localization for the post-operative improvement of balance and gait is unknown. Methods: In this single-center, retrospective analyses, 66 Parkinson's disease (PD) patients (24 female, age 63 ± 7 years) were assessed pre- and post-operatively (8.45 ± 4.2 months after surgery) by using MDS-UPDRS, freezing of gait (FoG) score, Giladi's gait and falls questionnaire and Berg balance scale. The clinical outcome was related to the DBS electrode coordinates in x, y, z plane as revealed by image-based reconstruction (SureTune™). Binomial generalized linear mixed models with fixed-effect variables electrode asymmetry, parkinsonian subtype, medication, age class and clinical DBS induced changes were analyzed. Results: Subthalamic nucleus-deep brain stimulation improved all motor, balance and FoG scores in MED OFF condition, however there were heterogeneous results in MED ON condition. DBS electrode reconstructed coordinates impacted the responsiveness of axial symptoms. FoG and balance responders showed slightly more medially located STN electrode coordinates and less medio-lateral asymmetry of the electrode reconstructed coordinates across hemispheres compared to non-responders. Conclusion: Deep brain stimulation electrode reconstructed coordinates, particularly electrode asymmetry on the medio-lateral axis affected the post-operative responsiveness of balance and FoG symptoms in PD patients.

Effectiveness of preoxygenation by conventional face mask versus non-invasive ventilation in morbidly obese patients: measurable by the oxygen-reserve index?

Preoxygenation is a crucial manoeuvre for patients' safety, particularly for morbidly obese patients due to their reduced pulmonary reserve and increased risk for difficult airway situations. The oxygen reserve index (ORI™) was recently introduced as a new parameter of multiple wavelength pulse oximetry and has been advocated to allow assessment of hyperoxia [quantified by the resulting arterial oxygen partial pressure (PaO2)]. This study investigates if ORI can be used to evaluate the impact of two different preoxygenation manoeuvres on the grade of hyperoxia. Two preoxygenation manoeuvres were sequentially evaluated in 41 morbidly obese patients: First, breathing 100% oxygen for 5 min via standard face mask. Second, after achieving a second baseline, 5 min of non-invasive ventilation (NIV) with 100% oxygen. The effect of preoxygenation on ORI compared to PaO2 was evaluated and whether differences in the two preoxygenation manoeuvres can be monitored by ORI. Overall correlation of PaO2 and ORI was significant (Spearman-Rho coefficient of correlation 0.818, p < 0.001). However, ORI could not differentiate between the two preoxygenation manoeuvres although the PaO2 values for NIV preoxygenation were significantly higher compared to standard preoxygenation (median 505 mmHg (M1) vs. 550 mmHg (M3); p < 0.0001). In contrast, ORI values did not differ significantly (median 0.39 (M1) vs. 0.38 (M3); p = 0.758). Absolute values of ORI cannot be used to assess effectiveness of a preoxygenation procedure in bariatric patients, mainly because its range of discrimination is considerably lower than the high ranges of PaO2 attained by adequate preoxygenation. Trial registration German Clinical Trials Register: DRKS00025023 (retrospectively registered on April 16th, 2021).

Intraoperative impaired cerebrovascular autoregulation and delayed neurocognitive recovery after major oncologic surgery: a secondary analysis of pooled data.

Cerebral blood flow is tightly regulated by cerebrovascular autoregulation (CVA), and intraoperative impairment of CVA has been linked with perioperative neurocognitive disorders. We aim to assess whether impairment of CVA during major oncologic surgery is associated with delayed neurocognitive recovery (DNCR) postoperatively. We performed a secondary analysis of prospectively collected data. Patients were included if they had undergone complete pre- and postoperative neuropsychological assessments, continuous intraoperative measurement of CVA, and major oncologic surgery for visceral, urological, or gynecological cancer. Intraoperative CVA was measured using the time-correlation method based on near-infrared-spectroscopy, and DNCR was assessed with a neuropsychological test battery. A decline in cognitive function before hospital discharge compared with a preoperative baseline assessment was defined as DNCR. One hundred ninety-five patients were included in the analysis. The median age of the study population was 65 years (IQR: 60-68); 11 patients (5.6%) were female. Forty-one patients (21.0%) fulfilled the criteria for DNCR in the early postoperative period. We found a significant association between impaired intraoperative CVA and DNCR before hospital discharge (OR = 1.042 [95% CI: 1.005; 1.080], p = 0.028). The type of surgery (radical prostatectomy vs. other major oncologic surgery; OR = 0.269 [95% CI: 0.099; 0.728], p = 0.010) and premedication with midazolam (OR = 3.360 [95% CI: 1.039; 10.870], p = 0.043) were significantly associated with the occurrence of DNCR in the early postoperative period. Intraoperative impairment of CVA is associated with postoperative neurocognitive function early after oncologic surgery. Therefore, intraoperative monitoring of CVA may be a target for neuroprotective interventions. The initial studies were retrospectively registered with primary clinical trial registries recognized by the World Health Organization (ClinicalTrials.gov Identifiers: DRKS00010014, 21.03.2016 and NCT04101006, 24.07.2019).

Neurological symptoms and complications in predominantly hospitalized COVID-19 patients: Results of the European multinational Lean European Open Survey on SARS-Infected Patients (LEOSS).

BACKGROUND AND PURPOSE: During acute coronavirus disease 2019 (COVID-19) infection, neurological signs, symptoms and complications occur. We aimed to assess their clinical relevance by evaluating real-world data from a multinational registry. METHODS: We analyzed COVID-19 patients from 127 centers, diagnosed between January 2020 and February 2021, and registered in the European multinational LEOSS (Lean European Open Survey on SARS-Infected Patients) registry. The effects of prior neurological diseases and the effect of neurological symptoms on outcome were studied using multivariate logistic regression. RESULTS: A total of 6537 COVID-19 patients (97.7% PCR-confirmed) were analyzed, of whom 92.1% were hospitalized and 14.7% died. Commonly, excessive tiredness (28.0%), headache (18.5%), nausea/emesis (16.6%), muscular weakness (17.0%), impaired sense of smell (9.0%) and taste (12.8%), and delirium (6.7%) were reported. In patients with a complicated or critical disease course (53%) the most frequent neurological complications were ischemic stroke (1.0%) and intracerebral bleeding (ICB; 2.2%). ICB peaked in the critical disease phase (5%) and was associated with the administration of anticoagulation and extracorporeal membrane oxygenation (ECMO). Excessive tiredness (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.20-1.68) and prior neurodegenerative diseases (OR 1.32, 95% CI 1.07-1.63) were associated with an increased risk of an unfavorable outcome. Prior cerebrovascular and neuroimmunological diseases were not associated with an unfavorable short-term outcome of COVID-19. CONCLUSION: Our data on mostly hospitalized COVID-19 patients show that excessive tiredness or prior neurodegenerative disease at first presentation increase the risk of an unfavorable short-term outcome. ICB in critical COVID-19 was associated with therapeutic interventions, such as anticoagulation and ECMO, and thus may be an indirect complication of a life-threatening systemic viral infection.

Intraoperative quality assessment of tissue perfusion with indocyanine green (ICG) in a porcine model of mesenteric ischemia.

BACKGROUND: Mesenteric ischemia is a severe and potentially lethal event. Assessment of intestine perfusion is eminently depending on the skills, and the experience of the surgeon. Thus, the therapy is biased by the right evaluation. Aim of this study is to determine the applicability, and the usefulness of fluorescent-imaging (FI) with indocyanine green (ICG) in a porcine model of mesenteric ischemia. Second end-point is the verification of a visual and quantitative assessment tool of the intestinal perfusion. METHODS: In 18 pigs (54,2 ±2,9kg) an occlusion of a side-branch of the mesenteric artery was performed for 3 (group I, n = 7), 6 (group II, n = 7), and 10 hours (group III, n = 4). After reperfusion a 60 minutes observation period was carried out. 3 regions of interest were defined: ischemic bowel (D1), transitional zone (D2), and non-ischemic bowel (D3). ICG-FI was performed during baseline (T0), occlusion (T1), reperfusion (T2) and after an observation period of 60 minutes (T4). RESULTS: All experiments could be finished successfully. ICG-FI was assessed using assessment of background-subtracted peak fluorescence intensity (BSFI), slope of fluorescence intensity (SFI), and a baseline adjusted ratio of both parameters. ICG-FI confirmed loss of perfusion in D1, decreased perfusion in D2, and increased perfusion in D3. After reperfusion ICG-FI increased in group 2 due to a severe tissue damage resulting in a capillary leakage. In group I ICG-FI was equal to baseline values indicating the totally reversible loss of perfusion. CONCLUSION: Using ICG-FI to estimate intestine perfusion after different durations of ischemia is viable using a porcine model of mesenteric ischemia. Even small differences in perfusion can be reliably determined by ICG-FI. Thus, ICG-FI is an encouraging method to evaluate intestine perfusion intraoperatively.

Sex-specific differences and long-term outcome of patients with coronary artery disease and chronic kidney disease: the Coronary Artery Disease and Renal Failure (CAD-REF) Registry.

BACKGROUND: Cardiovascular morbidity and mortality are closely linked to chronic kidney disease (CKD). Sex-specific long-term outcome data of patients with coronary artery disease (CAD) and CKD are scarce. METHODS: In the prospective observational multicenter Coronary Artery Disease and REnal Failure (CAD-REF) Registry, 773 (23.1%) women and 2,579 (76.9%) men with angiographically documented CAD and different stages of CKD were consecutively enrolled and followed for up to 8 years. Long-term outcome was evaluated using survival analysis and multivariable Cox-regression models. RESULTS: At enrollment, women were significantly older than men, and suffered from more comorbidities like CKD, hypertension, diabetes mellitus, and multivessel coronary disease. Regarding long-term mortality, no sex-specific differences were observed (Kaplan-Meier survival estimates: 69% in women vs. 69% in men, plog-rank = 0.7). Survival rates decreased from 89% for patients without CKD at enrollment to 72% for patients with CKD stages 1-2 at enrollment and 49% for patients with CKD stages 3-5 at enrollment (plog-rank < 0.001). Cox-regression analysis revealed that sex or multivessel coronary disease were no independent predictors of long-term mortality, while age, CKD stages 3-5, albumin/creatinine ratio, diabetes, valvular heart disease, peripheral artery disease, and left-ventricular ejection fraction were predictors of long-term mortality. CONCLUSIONS: Sex differences in CAD patients mainly exist in the cardiovascular risk profile and the extent of CAD. Long-term mortality was not depended on sex or multivessel disease. More attention should be given to treatment of comorbidities such as CKD and peripheral artery disease being independent predictors of death. Clinical Trail Registration ClinicalTrials.gov Identifier: NCT00679419.

Assessing volume responsiveness using right ventricular dynamic indicators of preload.

PURPOSE: Dynamic indicators of preload currently only do reflect preload requirements of the left ventricle. To date, no dynamic indicators of right ventricular preload have been established. The aim of this study was to calculate dynamic indicators of right ventricular preload and assess their ability to predict ventricular volume responsiveness. MATERIALS AND METHODS: The study was designed as experimental trial in 20 anaesthetized pigs. Micro-tip catheters and ultrasonic flow probes were used as experimental reference to enable measurement of right ventricular stroke volume and pulse pressure. Hypovolemia was induced (withdrawal of blood 20 ml/kg) and thereafter three volume-loading steps were performed. ROC analysis was performed to assess the ability of dynamic right ventricular parameters to predict volume response. RESULTS: ROC analysis revealed an area under the curve (AUC) of 0.82 (CI 95% 0.73-0.89; p < 0.001) for right ventricular stroke volume variation (SVVRV), an AUC of 0.72 (CI 95% 0.53-0.85; p = 0.02) for pulmonary artery pulse pressure variation (PPVPA) and an AUC of 0.66 (CI 95% 0.51-0.79; p = 0.04) for pulmonary artery systolic pressure variation (SPVPA). CONCLUSIONS: In our experimental animal setting, calculating dynamic indicators of right ventricular preload is possible and appears promising in predicting volume responsiveness.

The use of pulse pressure variation for predicting impairment of microcirculatory blood flow.

Dynamic parameters of preload have been widely recommended to guide fluid therapy based on the principle of fluid responsiveness and with regard to cardiac output. An equally important aspect is however to also avoid volume-overload. This accounts particularly when capillary leakage is present and volume-overload will promote impairment of microcirculatory blood flow. The aim of this study was to evaluate, whether an impairment of intestinal microcirculation caused by volume-load potentially can be predicted using pulse pressure variation in an experimental model of ischemia/reperfusion injury. The study was designed as a prospective explorative large animal pilot study. The study was performed in 8 anesthetized domestic pigs (German landrace). Ischemia/reperfusion was induced during aortic surgery. 6 h after ischemia/reperfusion-injury measurements were performed during 4 consecutive volume-loading-steps, each consisting of 6 ml kg-1 bodyweight-1. Mean microcirculatory blood flow (mean Flux) of the ileum was measured using direct laser-speckle-contrast-imaging. Receiver operating characteristic analysis was performed to determine the ability of pulse pressure variation to predict a decrease in microcirculation. A reduction of ≥ 10% mean Flux was considered a relevant decrease. After ischemia-reperfusion, volume-loading-steps led to a significant increase of cardiac output as well as mean arterial pressure, while pulse pressure variation and mean Flux were significantly reduced (Pairwise comparison ischemia/reperfusion-injury vs. volume loading step no. 4): cardiac output (l min-1) 1.68 (1.02-2.35) versus 2.84 (2.15-3.53), p = 0.002, mean arterial pressure (mmHg) 29.89 (21.65-38.12) versus 52.34 (43.55-61.14), p < 0.001, pulse pressure variation (%) 24.84 (17.45-32.22) versus 9.59 (1.68-17.49), p = 0.004, mean Flux (p.u.) 414.95 (295.18-534.72) versus 327.21 (206.95-447.48), p = 0.006. Receiver operating characteristic analysis revealed an area under the curve of 0.88 (CI 95% 0.73-1.00; p value < 0.001) for pulse pressure variation for predicting a decrease of microcirculatory blood flow. The results of our study show that pulse pressure variation does have the potential to predict decreases of intestinal microcirculatory blood flow due to volume-load after ischemia/reperfusion-injury. This should encourage further translational research and might help to prevent microcirculatory impairment due to excessive fluid resuscitation and to guide fluid therapy in the future.

Virtual reality as a teaching method for resuscitation training in undergraduate first year medical students: a randomized controlled trial.

BACKGROUND: Virtual reality is an innovative technology for medical education associated with high empirical realism. Therefore, this study compares a conventional cardiopulmonary resuscitation (CPR) training with a Virtual Reality (VR) training aiming to demonstrate: (a) non-inferiority of the VR intervention in respect of no flow time and (b) superiority in respect of subjective learning gain. METHODS: In this controlled randomized study first year, undergraduate students were allocated in the intervention group and the control group. Fifty-six participants were randomized to the intervention group and 104 participants to the control group. The intervention group received an individual 35-min VR Basic Life Support (BLS) course and a basic skill training. The control group took part in a "classic" BLS-course with a seminar and a basic skill training. The groups were compared in respect of no flow time in a final 3-min BLS examination (primary outcome) and their learning gain (secondary outcome) assessed with a comparative self-assessment (CSA) using a questionnaire at the beginning and the end of the course. Data analysis was performed with a general linear fixed effects model. RESULTS: The no flow time was significantly shorter in the control group (Mean values: control group 82 s vs. intervention group 93 s; p = 0.000). In the CSA participants of the intervention group had a higher learning gain in 6 out of 11 items of the questionnaire (p < 0.05). CONCLUSION: A "classic" BLS-course with a seminar and training seems superior to VR in teaching technical skills. However, overall learning gain was higher with VR. Future BLS course-formats should consider the integration of VR technique into the classic CPR training or vice versa, to use the advantage of both teaching techniques.