[Patient concerns and palliative psychology interventions within an inpatient palliative care service]. / Patientenseitige Anliegen und palliativpsychologische Interventionen im Rahmen eines stationären Palliativdienstes.

BACKGROUND: Multi-professional inpatient palliative care services are increasingly complementing palliative care in hospitals alongside palliative care units. The present study aims to investigate the nature and frequency of patient concerns and palliative psychological interventions in the context of palliative psychological work, as well as the perceived quality of outcomes in an inpatient palliative service. METHODS: Palliative psychological interventions for terminally ill patients at the inpatient palliative care service at Leipzig University Hospital were investigated in a prospective follow-up evaluation study. Psychological distress (distress thermometer) as well as the perceived quality of the results of the palliative psychological support (from the therapist`s perspective) were recorded. Patient concerns and psychological conversation topics and interventions were recorded. Descriptive and regression analytic procedures were used. RESULTS: Over a year, 355 patients in the inpatient palliative care service received psychological support, 304 participated in the study (mean age 63.8 years, 55% male, 89% oncological disease). An average of 3 palliative psychological interviews were conducted; 64% of patients reported high psychological distress (M=6.5). The most common patient concerns and topics within the interviews were dealing with emotions (87%), resources (83%), conflicting care and autonomy issues (77%) and hope (76%); significantly less common were spiritual concerns (2%) or the patient's legacy (9%). The most frequently used palliative psychological interventions included: support in illness processing and acceptance (74%) or in emotional-relieving interventions (98%) as in normalisation (75%), active listening (97%) or emotional containment (95%). Regression analysis showed that an oncological (vs. non-oncological) disease, a high number of palliative psychological interviews and interventions, comprehensive information regarding the palliative dimension of the diagnosis as well as undisturbed contact in the initial interview had a positive effect on the perceived outcome quality. CONCLUSION: The study results show that palliative psychologists play an important role in inpatient palliative care teams and should be involved as early as possible in the course of the disease. There is a need for improvement, especially in the palliative psychological care of non-oncological patients.

[Measures and Recommendations for Ensuring Adequate Inpatient Care Capacities for Pandemic Management within a Region: Results of a Hybrid Delphi Method]. / Maßnahmen und Empfehlungen für die Sicherstellung adäquater stationärer Versorgungskapazitäten für das Pandemiemanagement innerhalb einer Region ­ Ergebnisse eines hybriden Delphi-Verfahrens.

INTRODUCTION: Since the beginning of the pandemic in spring 2020, inpatient healthcare has been under enormous burden, which is reflected especially in overworked staff, imprecise bed planning and/or data transfer. According to the recommendation of the Science Council, university clinics should play a controlling role in regional healthcare and act in conjunction with surrounding hospitals and practices. METHODS: In September 2021, 31 representatives from 18 university hospitals were invited to a hybrid Delphi study with a total of 4 survey rounds to discuss criteria for effective inpatient care in a pandemic situation, which were extracted from previous expert interviews. Criteria that were classified as very important/relevant by≥75% of the participants in the first round of the survey (consensus definition) were then further summarized in 4 different small groups. In a third Delphi round, all participants came together again to discuss the results of the small group discussions. Subsequently, these were prioritized as Optional ("can"), Desirable ("should") or Necessary ("must") recommendations. RESULTS: Of the invited clinical experts, 21 (67.7%) participated in at least one Delphi round. In an online survey (1st Delphi round), 233 criteria were agreed upon and reduced to 84 criteria for future pandemic management in four thematic small group discussions (2nd Delphi round) and divided into the small groups as follows: "Crisis Management and Crisis Plans" (n=20), "Human Resources Management and Internal Communication" (n=16), "Regional Integration and External Communication" (n=24) and "Capacity Management and Case & Care" (n=24). In the following group discussion (3rd Delphi round), the criteria were further modified and agreed upon by the experts, so that in the end result, there were 23 essential requirements and recommendations for effective inpatient care in a pandemic situation. CONCLUSION: The results draw attention to key demands of clinical representatives, for example, comprehensive digitization, standardization of processes and better (supra) regional networking in order to be able to guarantee needs-based care even under pandemic conditions. The present consensus recommendations can serve as guidelines for future pandemic management in the inpatient care sector.

Development and consensus of entrustable professional activities for final-year medical students in anaesthesiology.

BACKGROUND: The transfer of classic concepts of competency-based medical education into clinical practice has been proven to be difficult in the past, being described as partially fragmented, misleading and inadequate. At the beginning of training, novice doctors commonly feel overwhelmed, overloaded and exposed to extreme time pressure. The discrepancy between expected and actual clinical competence of doctors at the start of their speciality training jeopardizes patient safety. The framework of Entrustable Professional Activities (EPAs) is a promising instrument to effectively integrate competency-based training into clinical practice and may help to close this gap and consequently to improve patient safety. METHODS: For anaesthesiology, we developed 5 EPAs for final-year medical students. The EPAs comprised the following seven categories: 1. Title, 2. Specifications, 3. Limitations, 4. Competency domains, 5. Knowledge, abilities and skills, professional attitudes, 6. Assessment and 7. Entrustment. Based on a modified, online-based Delphi study, we further developed and refined these EPAs. Education experts were recruited from the alumni network of the Master of Medical Education (MME) degree course from the University of Heidelberg, Germany. RESULTS: 28 data sets were evaluated in three Delphi rounds. 82% of study participants had previous experience with EPAs. Qualitative and quantitative data formed the basis during the iterative process and resulted in complete descriptions of 5 EPAs for final-year medical students in anaesthesiology. CONCLUSIONS: Our study including the associated description of 5 EPAs represent a further step and starting point for EPA-based curricula in medical training in Germany linking undergraduate training, to residency training and continuous medical education.

[The cross-sectional field "pain medicine" in medical studies at the University of Leipzig-What has been achieved? : An analysis of self-estimation of students before, during and 5 years after establishment of the cross-sectional field]. / Der Querschnittsbereich 14 "Schmerzmedizin" an der Universität Leipzig ­ was wurde erreicht? : Eine Analyse der Selbsteinschätzung der Studierenden vor, während und fünf Jahre nach Etablierung des Querschnittsbereichs.

BACKGROUND: The field of pain medicine was established as an obligatory subject area of medical schools in Germany in 2016. No prior study has evaluated the effects of this curricular change on students' competences in the field of pain medicine. OBJECTIVE: The aim of this study was to find out to what extent the introduction of the additional subject "pain medicine" positively influenced the students' acquisition of competences measured via a self-assessment. MATERIAL AND METHODS: A longitudinal and interdisciplinary curriculum for pain medicine was developed according to the current recommendations for curriculum development for medical education. In parallel, a questionnaire was created for the students' self-assessment of their own level of knowledge and the importance of pain medicine teaching content on a 5-stage Likert scale. The surveys were conducted before the implementation of the curriculum (2014), directly after the first cohort finished (2016) and 5 years after the implementation (2019) and compared by Kruskal-Wallis test. RESULTS: The implementation of the curriculum has led to significant improvement in relevant aspects. For example, students now feel better prepared overall for the treatment of pain patients (2.67 in 2014 vs. 3.18 in 2019). Individual sub-aspects such as taking a pain history (3.63 vs. 4.10) or drawing up an analgesia scheme (3.56 vs. 4.14) are now also subjectively better mastered. CONCLUSION: Even though the results are encouraging, there is further potential for improvement in some sub-areas. For example, the students' rating regarding the question about their preparation for treating patients in pain is not yet satisfactory. Therefore, the curriculum should be developed further with a focus on competence orientation. Digital teaching formats can be integrated as well as interprofessional units and simulated patients. Additionally, the examination formats should be further developed towards standardized practical examinations.

[COVID-19: a chance for digitalization of teaching? : Report of experiences and results of a survey on digitalized teaching in the fields of anesthesiology, intensive care, emergency, pain and palliative medicine at the University of Leipzig]. / COVID-19: eine Chance zur Digitalisierung der Lehre? : Erfahrungsbericht und Ergebnisse einer Umfrage zur digitalen Lehre im Bereich Anästhesiologie, Intensiv-, Notfall-, Schmerz- und Palliativmedizin an der Universität Leipzig.

BACKGROUND: The SARS-CoV­2 pandemic has been a major challenge for graduate education. Teaching had to be digitalized within a very short time. This also affected the areas of anesthesiology, intensive care, emergency, pain and palliative care at the Department of Anesthesiology and Intensive Care Medicine at the University of Leipzig. OBJECTIVE: The aim of this questionnaire-based survey was to find out which courses can be digitalized from the students' point of view and which forms of teaching are associated with obstacles. In addition, we examined which technical infrastructure supports digitalization best. MATERIAL AND METHODS: In the course of digitalization the lecture series in the areas of palliative care and pain medicine had to be revised but also digital alternatives for seminars, simulation courses and bedside teaching had to be created. Video podcasts, digital learning material, educational films and video conferences were used for the digital implementation of the courses. Depending on the course, different digital methods were combined. In addition, a discussion forum for the exchange between faculty and students was established. An online evaluation was then carried out to assess the content. RESULTS: A total of 82 4th and 5th year medical students took part in the survey. More than 60% of students rated the learning effect of digital courses as "high" or "very high". Video podcasts of the lectures (45.1%) and digital bedside teaching (34.1%) were rated as the most effective ways of imparting knowledge. In particular, 92.7% of the surveyed students believed that the lectures could be replaced digitally on a permanent basis. For bedside teaching (3.7%) and emergency simulation course (1.2%) this is far less the case. In the majority of cases (56.1%), students needed 30-90 min daily for the preparation and post-processing of the contents. Just under 90% gave the digital courses offered by the hospital an overall grade of 1 or 2 (on a scale from 1 = best to 6 = worst). CONCLUSION: The SARS-CoV­2 pandemic posed major challenges for graduate teaching. At the same time, however, it also helped to overcome often long-standing hurdles to the digitalization of teaching. In the course of the digital semester, different teaching formats could be digitalized to varying degrees: Lectures can be digitally reproduced particularly well from the students' perspective, whereas the digitalization of bedside teaching has not been possible in most cases.

HIF-driven SF3B1 induces KHK-C to enforce fructolysis and heart disease.

Fructose is a major component of dietary sugar and its overconsumption exacerbates key pathological features of metabolic syndrome. The central fructose-metabolising enzyme is ketohexokinase (KHK), which exists in two isoforms: KHK-A and KHK-C, generated through mutually exclusive alternative splicing of KHK pre-mRNAs. KHK-C displays superior affinity for fructose compared with KHK-A and is produced primarily in the liver, thus restricting fructose metabolism almost exclusively to this organ. Here we show that myocardial hypoxia actuates fructose metabolism in human and mouse models of pathological cardiac hypertrophy through hypoxia-inducible factor 1α (HIF1α) activation of SF3B1 and SF3B1-mediated splice switching of KHK-A to KHK-C. Heart-specific depletion of SF3B1 or genetic ablation of Khk, but not Khk-A alone, in mice, suppresses pathological stress-induced fructose metabolism, growth and contractile dysfunction, thus defining signalling components and molecular underpinnings of a fructose metabolism regulatory system crucial for pathological growth.

Non-medical risk factors associated with postponing elective surgery: a prospective observational study.

BACKGROUND: Operation room (OR) planning is a complex process, especially in large hospitals with high rates of unplanned emergency procedures. Postponing elective surgery in order to provide capacity for emergency operations is inevitable at times. Elderly patients, residents of nursing homes, women, patients with low socioeconomic status and ethnic minorities are at risk for undertreatment in other contexts, as suggested by reports in the medical literature. We hypothesized that specific patient groups could be at higher risk for having their elective surgery rescheduled for non-medical reasons. METHODS: In this single center, prospective observational trial, we analysed 2519 patients undergoing elective surgery from October 2018 to May 2019. A 14-item questionnaire was handed out to illicit patient details. Additional characteristics were collected using electronic patient records. Information on the timely performance of the scheduled surgery was obtained using the OR's patient data management system. 6.45% of all planned procedures analysed were postponed. Association of specific variables with postponement rates were analysed using the Mann-Whitney U test and Fisher's exact test/χ2-test. RESULTS: Significantly higher rates of postponing elective surgery were found in elderly patients. No significant differences in postponing rates were found for the variables gender, nationality (Germany, EU, non-EU), native language, professional medical background and level of education. Significantly lower rescheduling rates were found in patients with ties to hospital staff and in patients with a private health insurer. CONCLUSIONS: Elderly patients, retirees and nursing home residents seem to be at higher risk for having their elective surgery rescheduled. However, owing to the study design, causality could not be proven. Our findings raise concern about possible undertreatment of these patient groups and provide data on short-term postponement of elective surgery. Trial registration DRKS00015836. Retrospectively registered.

Inhibition of the Hypoxia-Inducible Factor 1α-Induced Cardiospecific HERNA1 Enhance-Templated RNA Protects From Heart Disease.

BACKGROUND: Enhancers are genomic regulatory elements conferring spatiotemporal and signal-dependent control of gene expression. Recent evidence suggests that enhancers can generate noncoding enhancer RNAs, but their (patho)biological functions remain largely elusive. METHODS: We performed chromatin immunoprecipitation-coupled sequencing of histone marks combined with RNA sequencing of left ventricular biopsies from experimental and genetic mouse models of human cardiac hypertrophy to identify transcripts revealing enhancer localization, conservation with the human genome, and hypoxia-inducible factor 1α dependence. The most promising candidate, hypoxia-inducible enhancer RNA ( HERNA)1, was further examined by investigating its capacity to modulate neighboring coding gene expression by binding to their gene promoters by using chromatin isolation by RNA purification and λN-BoxB tethering-based reporter assays. The role of HERNA1 and its neighboring genes for pathological stress-induced growth and contractile dysfunction, and the therapeutic potential of HERNA1 inhibition was studied in gapmer-mediated loss-of-function studies in vitro using human induced pluripotent stem cell-derived cardiomyocytes and various in vivo models of human pathological cardiac hypertrophy. RESULTS: HERNA1 is robustly induced on pathological stress. Production of HERNA1 is initiated by direct hypoxia-inducible factor 1α binding to a hypoxia-response element in the histoneH3-lysine27acetylation marks-enriched promoter of the enhancer and confers hypoxia responsiveness to nearby genes including synaptotagmin XVII, a member of the family of membrane-trafficking and Ca2+-sensing proteins and SMG1, encoding a phosphatidylinositol 3-kinase-related kinase. Consequently, a substrate of SMG1, ATP-dependent RNA helicase upframeshift 1, is hyperphoshorylated in a HERNA1- and SMG1-dependent manner. In vitro and in vivo inactivation of SMG1 and SYT17 revealed overlapping and distinct roles in modulating cardiac hypertrophy. Finally, in vivo administration of antisense oligonucleotides targeting HERNA1 protected mice from stress-induced pathological hypertrophy. The inhibition of HERNA1 postdisease development reversed left ventricular growth and dysfunction, resulting in increased overall survival. CONCLUSIONS: HERNA1 is a novel heart-specific noncoding RNA with key regulatory functions in modulating the growth, metabolic, and contractile gene program in disease, and reveals a molecular target amenable to therapeutic exploitation.

Genome-wide association study of myocardial infarction, atrial fibrillation, acute stroke, acute kidney injury and delirium after cardiac surgery - a sub-analysis of the RIPHeart-Study.

BACKGROUND: The aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery. METHODS: We conducted a prospective, double-blind, multicenter, randomized trial (RIPHeart). We performed a genome-wide association study (GWAS) in 1170 patients of both genders (871 males, 299 females) from the RIPHeart-Study cohort. Patients undergoing non-emergent cardiac surgery were included. Primary endpoint comprises a binary composite complication rate covering atrial fibrillation, delirium, non-fatal myocardial infarction, acute renal failure and/or any new stroke until hospital discharge with a maximum of fourteen days after surgery. RESULTS: A total of 547,644 genotyped markers were available for analysis. Following quality control and adjustment for clinical covariate, one SNP reached genome-wide significance (PHLPP2, rs78064607, p = 3.77 × 10- 8) and 139 (adjusted for all other outcomes) SNPs showed promising association with p < 1 × 10- 5 from the GWAS. CONCLUSIONS: We identified several potential loci, in particular PHLPP2, BBS9, RyR2, DUSP4 and HSPA8, associated with new-onset of atrial fibrillation, delirium, myocardial infarction, acute kidney injury and stroke after cardiac surgery. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010.

A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery.

BACKGROUND: Remote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery, but uncertainty about clinical outcomes remains. METHODS: We conducted a prospective, double-blind, multicenter, randomized, controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol. The trial compared upper-limb RIPC with a sham intervention. The primary end point was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary end points included the occurrence of any individual component of the primary end point by day 90. RESULTS: A total of 1403 patients underwent randomization. The full analysis set comprised 1385 patients (692 in the RIPC group and 693 in the sham-RIPC group). There was no significant between-group difference in the rate of the composite primary end point (99 patients [14.3%] in the RIPC group and 101 [14.6%] in the sham-RIPC group, P=0.89) or of any of the individual components: death (9 patients [1.3%] and 4 [0.6%], respectively; P=0.21), myocardial infarction (47 [6.8%] and 63 [9.1%], P=0.12), stroke (14 [2.0%] and 15 [2.2%], P=0.79), and acute renal failure (42 [6.1%] and 35 [5.1%], P=0.45). The results were similar in the per-protocol analysis. No treatment effect was found in any subgroup analysis. No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release, the duration of mechanical ventilation, the length of stay in the intensive care unit or the hospital, new onset of atrial fibrillation, and the incidence of postoperative delirium. No RIPC-related adverse events were observed. CONCLUSIONS: Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery. (Funded by the German Research Foundation; RIPHeart ClinicalTrials.gov number, NCT01067703.).

In Vitro Negative Inotropic Effect of Low Concentrations of Bupivacaine Relates to Diminished Ca2+ Sensitivity but Not to Ca2+ Handling or ß-Adrenoceptor Signaling.

BACKGROUND: Systemic toxicity of local anesthetics is predominantly complicated by their myocardial toxicity. Especially long-acting local anesthetics exert a negative inotropic effect that has been described at lower concentrations than defined for blockade of myocardial ion channels. We evaluated the negative inotropic effect of bupivacaine at a concentration described for clinical toxicity testing the hypothesis that negative inotropy is a result of reduced Ca sensitivity rather than blockade of ion channels. METHODS: We simultaneously measured force development and action potentials in guinea pig right papillary muscles (n = 5 to 7). L-type Ca currents (n = 8 to 16) and Ca transients (n = 10 to 11) were measured in isolated cardiomyocytes. Sensitivity of myofilaments to Ca was assessed in skinned fibers (n = 10). Potential effects of bupivacaine on 3',5'-cyclic adenosine monophosphate concentrations were measured using Förster Resonance Energy Transfer (n = 12 to 14) microscopy. RESULTS: Bupivacaine reduced force in a concentration-dependent manner from 173 ± 119 µN at baseline to 28 ± 13 µN at 300 µM (mean ± SD). At concentrations giving half-maximum negative inotropic effects (5 µM), the maximum upstroke velocity of action potentials, as a surrogate of sodium channel activity, was unaffected. Maximum positive inotropic effects of isoprenaline were also reduced to 50%. Neither basal nor isoprenaline-induced 3',5'-cyclic adenosine monophosphate accumulation, L-type Ca currents, or Ca transients were affected by 5 µM bupivacaine, but this concentration significantly decreased Ca sensitivity of myofilaments, changing the negative logarithm of the half-maximum effective Ca concentrations from 5.66 to 5.56 -log[M]. CONCLUSIONS: We provide evidence that the negative inotropic effect of bupivacaine may be caused mainly by a reduction in myofilament sensitivity to Ca.

Adjustment of Dysregulated Ceramide Metabolism in a Murine Model of Sepsis-Induced Cardiac Dysfunction.

Cardiac dysfunction, in particular of the left ventricle, is a common and early event in sepsis, and is strongly associated with an increase in patients' mortality. Acid sphingomyelinase (SMPD1)-the principal regulator for rapid and transient generation of the lipid mediator ceramide-is involved in both the regulation of host response in sepsis as well as in the pathogenesis of chronic heart failure. This study determined the degree and the potential role to which SMPD1 and its modulation affect sepsis-induced cardiomyopathy using both genetically deficient and pharmacologically-treated animals in a polymicrobial sepsis model. As surrogate parameters of sepsis-induced cardiomyopathy, cardiac function, markers of oxidative stress as well as troponin I levels were found to be improved in desipramine-treated animals, desipramine being an inhibitor of ceramide formation. Additionally, ceramide formation in cardiac tissue was dysregulated in SMPD1+/+ as well as SMPD1-/- animals, whereas desipramine pretreatment resulted in stable, but increased ceramide content during host response. This was a result of elevated de novo synthesis. Strikingly, desipramine treatment led to significantly improved levels of surrogate markers. Furthermore, similar results in desipramine-pretreated SMPD1-/- littermates suggest an SMPD1-independent pathway. Finally, a pattern of differentially expressed transcripts important for regulation of apoptosis as well as antioxidative and cytokine response supports the concept that desipramine modulates ceramide formation, resulting in beneficial myocardial effects. We describe a novel, protective role of desipramine during sepsis-induced cardiac dysfunction that controls ceramide content. In addition, it may be possible to modulate cardiac function during host response by pre-conditioning with the Food and Drug Administration (FDA)-approved drug desipramine.

[Perioperative heart failure - preoperative approach]. / Perioperative Herzinsuffizienz - Präoperative Einschätzung.

Heart failure is a common disease which is associated with an increased perioperative risk. In the following, we summarize pathophysiology, momentary treatment options and a preoperative approach to patients with heart failure.

Myocardial accumulation of bupivacaine and ropivacaine is associated with reversible effects on mitochondria and reduced myocardial function.

BACKGROUND: Mechanisms of local anesthetic cardiac toxicity are still not completely understood. In this study, we analyzed whether concentrations of local anesthetics found in clinical toxicity affect myocardial mitochondrial structure and oxygen consumption. METHODS: Guinea pig isolated heart Langendorff preparations were exposed to bupivacaine (3.0 and 7.5 µg/mL) and ropivacaine (3.6 and 9.0 µg/mL) for 10 minutes. Heart rate, systolic blood pressure, the first derivative of left ventricular pressure (+dP/dt), electrocardiogram, and coronary flow were recorded. The local anesthetic tissue concentration was measured either immediately after local anesthetic exposure, or after 20- and 60-minute washout periods. In addition, electron microscopy of myocardial mitochondria was performed using a scoring system for structural damage of mitochondria. Cardiomyocyte cell culture was incubated with bupivacaine, and oxygen consumption ratio, extracellular acidification, and relative amounts of PGC-1α mRNA, a regulator of cellular energy metabolism, were determined. RESULTS: Bupivacaine and ropivacaine induced reversible PR interval and QRS prolongation, and left ventricular pressure and +dP/dt reduction. Myocardial tissue concentration of local anesthetics was 3-fold the arterial concentration. Mitochondria showed a significant concentration-dependent morphological swelling after local anesthetic application. These changes were reversed by a 20-minute washout period for ropivacaine and by a 60-minute washout for bupivacaine. Bupivacaine reduced mitochondrial oxygen consumption and increased PGC-1α expression in neonatal cardiomyocyte cell cultures, whereas fatty acid metabolism remained unaffected. CONCLUSIONS: Bupivacaine and ropivacaine accumulate in the myocardium. Reversible local anesthetic-induced mitochondrial swelling occurs at concentrations that induce a negative inotropic effect. Bupivacaine reduces cellular metabolism, whereas this reduction is reversible by fatty acids. Interaction with mitochondria may contribute to the negative inotropic effect of local anesthetics.

Remote ischaemic preconditioning for heart surgery. The study design for a multi-center randomized double-blinded controlled clinical trial--the RIPHeart-Study.

AIMS: Transient ischaemia of non-vital tissue has been shown to enhance the tolerance of remote organs to cope with a subsequent prolonged ischaemic event in a number of clinical conditions, a phenomenon known as remote ischaemic preconditioning (RIPC). However, there remains uncertainty about the efficacy of RIPC in patients undergoing cardiac surgery. The purpose of this report is to describe the design and methods used in the "Remote Ischaemic Preconditioning for Heart Surgery (RIPHeart)-Study". METHODS: We are conducting a prospective, randomized, double-blind, multicentre, controlled trial including 2070 adult cardiac surgical patients. All types of surgery in which cardiopulmonary bypass is used will be included. Patients will be randomized either to the RIPC group receiving four 5 min cycles of transient upper limb ischaemia/reperfusion or to the control group receiving four cycles of blood pressure cuff inflation/deflation at a dummy arm. The primary endpoint is a composite outcome (all-cause mortality, non-fatal myocardial infarction, any new stroke, and/or acute renal failure) until hospital discharge. CONCLUSION: The RIPHeart-Study is a multicentre trial to determine whether RIPC may improve clinical outcome in cardiac surgical patients.

Prognostic Factors for Postoperative Bleeding Complications and Prolonged Intensive Care after Percutaneous Hepatic Chemosaturation Procedures with Melphalan.

Percutaneous hepatic melphalan perfusion (chemosaturation) in patients with liver metastases is known to be associated with procedure-related hemodynamic depression and coagulation impairment, which may cause bleeding complications and/or a prolonged intensive care unit length of stay (ICU LOS). We retrospectively analyzed possible predictive factors for bleeding complications and an ICU LOS > 1 d in a cohort of 31 patients undergoing 90 chemosaturation procedures. Using a multivariable mixed-model approach, we identified the amount of perioperative fluid volume (OR 12.0, 95% CI 2.3-60.0, p = 0.003) and protamine (OR 0.065, 95% CI 0.007-0.55, p = 0.012) to be associated with bleeding complications. Furthermore, the amount of perioperative fluid volume was associated with an ICU LOS > 1 d (OR 5.2, 95% CI 1.4-19.0, p = 0.011). Heparin dosage, melphalan dosage, extracorporeal circulation time, and noradrenaline dosage had no significant effects on outcomes. Protamine use was not associated with anaphylactic or thromboembolic complications. Despite the limited sample size, these results suggest a restrictive perioperative fluid regime to be beneficial, and support the use of protamine for heparin reversal after chemosaturation procedures. Further prospective randomized trials are needed to confirm these findings.

[Anesthesiological and postinterventional management in percutaneous hepatic melphalan perfusion (chemosaturation)]. / Anästhesiologisches und postinterventionelles Management bei perkutaner hepatischer Melphalanperfusion (Chemosaturation).

Percutaneous hepatic melphalan perfusion (PHMP) is a last-line treatment of inoperable primary or secondary liver tumors. Selective perfusion and saturation (chemosaturation) of the liver with the chemotherapeutic agent melphalan is performed via catheterization of the hepatic artery without affecting the rest of the body with its cytotoxic properties. Using an extracorporeal circulation and balloon occlusion of the inferior vena cava, the venous hepatic blood is filtered and returned using a bypass procedure. During the procedure, considerable circulatory depression and coagulopathy are frequent. The purpose of this article is to review the anesthesiological and postprocedural management of patients undergoing PHMP with consideration of the pitfalls and special circumstances.

SARS-CoV-2 Vaccine Breakthrough Infections of Omicron and Delta Variants in Healthcare Workers.

Understanding SARS-CoV-2 breakthrough infections in vaccinated healthcare workers is of key importance in mitigating the effects of the COVID-19 pandemic in healthcare facilities. An observational prospective cohort study was conducted in vaccinated employees with acute SARS-CoV-2 infection between October 2021 and February 2022. Serological and molecular testing was performed to determine SARS-CoV-2 viral load, lineage, antibody levels, and neutralizing antibody titers. A total of 571 (9.7%) employees experienced SARS-CoV-2 breakthrough infections during the enrolment period, of which 81 were included. The majority (n = 79, 97.5%) were symptomatic and most (n = 75, 92.6%) showed Ct values < 30 in RT-PCR assays. Twenty-four (30%) remained PCR-positive for > 15 days. Neutralizing antibody titers were strongest for the wildtype, intermediate for Delta, and lowest for Omicron variants. Omicron infections occurred at higher anti-RBD-IgG serum levels (p = 0.00001) and showed a trend for higher viral loads (p = 0.14, median Ct difference 4.3, 95% CI [-2.5-10.5]). For both variants, viral loads were significantly higher in participants with lower anti-RBD-IgG serum levels (p = 0.02). In conclusion, while the clinical course of infection with both the Omicron and Delta variants was predominantly mild to moderate in our study population, waning immune response over time and prolonged viral shedding were observed.

Burden of hospital admissions and resulting patient interhospital transports during the 2020/2021 SARS-CoV-2 pandemic in Saxony, Germany.

Secondary transports of patients from one hospital to another are indicated for medical reasons or to address local constraints in capacity. In particular, interhospital transports of critically ill infectious patients present a logistical challenge and can be key in the effective management of pandemic situations. The state of Saxony in Germany has two characteristics that allow for an extensive evaluation of secondary transports in the pandemic year 2020/2021. First, all secondary transports are centrally coordinated by a single institution. Second, Saxony had the highest SARS-CoV-2 infection rates and the highest COVID-19 associated mortality in Germany. This study evaluates secondary interhospital transports from March 2019 to February 2021 in Saxony with a detailed analysis of transport behaviour during the pandemic phase March 2020 to February 2021. Our analysis includes secondary transports of SARS-CoV-2 patients and compares them to secondary transports of non-infectious patients. In addition, our data show differences in demographics, SARS-CoV-2- incidences, ICU occupancy of COVID-19 patients, and COVID-19 associated mortality in all three regional health clusters in Saxony. In total, 12,282 secondary transports were analysed between March 1st, 2020 and February 28th, 2021, of which 632 were associated with SARS-CoV-2 (5.1%) The total number of secondary transports changed slightly during the study period March 2020 to February 2021. Transport capacities for non-infectious patients were reduced due to in-hospital and out-of-hospital measures and could be used for transport of SARS-CoV-2 patients. Infectious transfers lasted longer despite shorter distance, occurred more frequently on weekends and transported patients were older. Primary transport vehicles were emergency ambulances, transport ambulances and intensive care transport vehicles. Data analysis based on hospital structures showed that secondary transports in correlation to weekly case numbers depend on the hospital type. Maximum care hospitals and specialized hospitals show a maximum of infectious transports approximately 4 weeks after the highest incidences. In contrast, standard care hospitals transfer their patients at the time of highest SARS-CoV-2 case numbers. Two incidence peaks were accompanied by two peaks of increased secondary transport. Our findings show that interhospital transfers of SARS-CoV-2 and non-SARS-CoV-2 patients differ and that different hospital care levels initiated secondary transports at different times during the pandemic.