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Objectives Suicide is a leading cause of death in the United States, and rates vary by race and ethnicity. An analysis of suicide across large US cities is absent from the literature. The objective of this study was to examine suicide rates among the total population, non-Hispanic Black population, and non-Hispanic White population in the United States and in the 30 largest US cities. Methods We used data from the National Vital Statistics System to calculate non-Hispanic White, non-Hispanic Black, and total age-adjusted suicide rates for the 30 largest US cities and for the entire nation during 2 periods: 2008-2012 and 2013-2017. We also examined absolute and relative differences in suicide rates among non-Hispanic White populations and non-Hispanic Black populations in each city. Results The overall age-adjusted suicide rate per 100 000 population in the United States increased significantly from 12.3 in 2008-2012 to 13.5 in 2013-2017. Total suicide rates were stable in most cities; rates increased significantly in only 1 city (Louisville), and rates decreased significantly in 2 cities (Boston and Memphis). The non-Hispanic White suicide rate was significantly higher—1.3 to 4.3 times higher—than the non-Hispanic Black suicide rate in 24 of 26 study cities during 2013-2017. From 2008-2012 to 2013-2017, non-Hispanic White suicide rates decreased significantly in 3 cities and increased significantly in 3 cities; non-Hispanic Black suicide rates increased significantly in 5 cities and decreased in none. Absolute differences in suicide rates among non-Hispanic White populations and non-Hispanic Black populations increased significantly in 1 city (Louisville) and decreased significantly in 2 cities (Memphis and Boston). Conclusions Our study may inform the use of evidence-based programs and practices to address population-level risk factors for suicide.

Acquired von Willebrand syndrome (aVWS) has been reported in patients with congenital heart diseases associated with shear stress caused by significant blood flow gradients. Its etiology and impact on intraoperative bleeding during pediatric cardiac surgery have not been systematically studied. This single-center, prospective, observational study investigated appropriate diagnostic tools of aVWS compared with multimer analysis as diagnostic criterion standard and aimed to clarify the role of aVWS in intraoperative hemorrhage. A total of 65 newborns and infants aged 0 to 12 months scheduled for cardiac surgery at our tertiary referral center from March 2018 to July 2019 were included in the analysis. The glycoprotein Ib M assay (GPIbM)/von Willebrand factor antigen (VWF:Ag) ratio provided the best predictability of aVWS (area under the receiver operating characteristic curve [AUC], 0.81 [95% CI, 0.75-0.86]), followed by VWF collagen binding assay/VWF:Ag ratio (AUC, 0.70 [0.63-0.77]) and peak systolic echocardiographic gradients (AUC, 0.69 [0.62-0.76]). A cutoff value of 0.83 was proposed for the GPIbM/VWF:Ag ratio. Intraoperative high-molecular-weight multimer ratios were inversely correlated with cardiopulmonary bypass (CPB) time (r = −0.57) and aortic cross-clamp time (r = −0.54). Patients with intraoperative aVWS received significantly more fresh frozen plasma (P = .016) and fibrinogen concentrate (P = .011) than those without. The amounts of other administered blood components and chest closure times did not differ significantly. CPB appears to trigger aVWS in pediatric cardiac surgery. The GPIbM/VWF:Ag ratio is a reliable test that can be included in routine intraoperative laboratory workup. Our data provide the basis for further studies in larger patient cohorts to achieve definitive clarification of the effects of aVWS and its potential treatment on intraoperative bleeding.

Purpose: Surgical interventions tend to have an effect on the generation of recurrences in tumor patients due to the anesthesia involved as well as tissue damage and subsequent inflammation. This can also be found in patients with breast cancer. Methods: In this multicenter study, we investigated data of 632 patients with breast cancer and the subsequent diagnosis of a recurrence. The patient data were acquired from 1 January 2006 to 31 December 2019 in eight different centers in Germany. The data sets were separated into those with primary surgery, primary systemic therapy with subsequent surgery, and reconstructive surgery. Three different starting points for observation were defined: the date of diagnosis, the date of first surgery, and the date of reconstructive surgery, if applicable. The observational period was divided into steps of six months and maxima of recurrences were compared. Furthermore, the variance was calculated using the difference of the distribution in percent. Results: The descriptive analysis showed no resemblance between the groups. The variance of the difference of the recurrence rates analysis using the surgical date as the starting point showed similarities in the age subgroup. Conclusion: Our clinical analysis shows different metastatic behavior in different analysis and treatment regimes. These findings justify further investigations on a larger database. These results may possibly identify an improved follow-up setting depending on tumor stage, biology, treatment, and patient factors (i.e., age, …).

Background: Oral activated factor XI (FXIa) inhibitors may modulate coagulation to prevent thromboembolic events without substantially increasing bleeding. We explored the pharmacodynamics, safety, and efficacy of the oral FXIa inhibitor asundexian for secondary prevention after acute myocardial infarction (MI). Methods: We randomized 1601 patients with recent acute MI to oral asundexian 10, 20, or 50 mg or placebo once daily for 6 to 12 months in a double-blind, placebo-controlled, phase 2, dose-ranging trial. Patients were randomized within 5 days of their qualifying MI and received dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor. The effect of asundexian on FXIa inhibition was assessed at 4 weeks. The prespecified main safety outcome was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding comparing all pooled asundexian doses with placebo. The prespecified efficacy outcome was a composite of cardiovascular death, MI, stroke, or stent thrombosis comparing pooled asundexian 20 and 50 mg doses with placebo. Results: The median age was 68 years, 23% of participants were women, 51% had ST-segment–elevation MI, 80% were treated with aspirin plus ticagrelor or prasugrel, and 99% underwent percutaneous coronary intervention before randomization. Asundexian caused dose-related inhibition of FXIa activity, with 50 mg resulting in >90% inhibition. Over a median follow-up of 368 days, the main safety outcome occurred in 30 (7.6%), 32 (8.1%), 42 (10.5%), and 36 (9.0%) patients receiving asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian versus placebo: hazard ratio, 0.98 [90% CI, 0.71–1.35]). The efficacy outcome occurred in 27 (6.8%), 24 (6.0%), 22 (5.5%), and 22 (5.5%) patients assigned asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian 20 and 50 mg versus placebo: hazard ratio, 1.05 [90% CI, 0.69–1.61]). Conclusions: In patients with recent acute MI, 3 doses of asundexian, when added to aspirin plus a P2Y12 inhibitor, resulted in dose-dependent, near-complete inhibition of FXIa activity without a significant increase in bleeding and a low rate of ischemic events. These data support the investigation of asundexian at a dose of 50 mg daily in an adequately powered clinical trial of patients who experienced acute MI. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04304534; URL: https://www.clinicaltrialsregister.eu/ctr-search/search ; Unique identifier: 2019-003244-79.

Purpose of reviewTraumatic brain injury (TBI) is a leading cause of trauma-related deaths, and pharmacologic interventions to limit intracranial bleeding should improve outcomes. Tranexamic acid reduces mortality in injured patients with major systemic bleeding, but the effects of antifibrinolytic drugs on outcomes after TBI are less clear. We therefore summarize recent evidence to guide clinicians on when (not) to use antifibrinolytic drugs in TBI patients.Recent findingsTranexamic acid is the only antifibrinolytic drug that has been studied in patients with TBI. Several recent studies failed to conclusively demonstrate a benefit on survival or neurologic outcome. A large trial with more than 12 000 patients found no significant effect of tranexamic acid on head-injury related death, all-cause mortality or disability across the overall study population, but observed benefit in patients with mild to moderate TBI. Observational evidence signals potential harm in patients with isolated severe TBI.SummaryGiven that the effect of tranexamic acid likely depends on a variety of factors, it is unlikely that a 'one size fits all' approach of administering antifibrinolytics to all patients will be helpful. Tranexamic acid should be strongly considered in patients with mild to moderate TBI and should be avoided in isolated severe TBI.

Since the establishment of neoadjuvant chemotherapy as the standard of care for patients with muscle invasive bladder cancer, the pathologic absence of disease, denoted pT0, was found to be predictive of improved overall survival. Accordingly, it has been used in clinical trials as an optimal surrogate outcome measure, even in contemporary nonchemotherapeutic interventions. We review the role of pT0 as a catalyst for change in trial design and its suitability to facilitate more efficient and timely results. In addition, we explore the present and future of cT0, the clinical absence of disease, in defining treatment response and enabling bladder-sparing management options.The use of pT0 as a surrogate has provided initial results for the efficacy of immunotherapy in the neoadjuvant space. In combination with molecular markers, pT0 has improved our ability to identify treatment responders and its clinical counterpart, cT0, has been integrated into multiple trials to redefine postneoadjuvant chemotherapy management algorithms.The use of pT0 as a surrogate endpoint in bladder cancer trials has improved clinical trial design, defined efficacy of emerging therapeutics, and has the potential to redefine the postneoadjuvant treatment management for patients seeking bladder-sparing options.

Aggressive pheochromocytomas and paragangliomas (PPGLs) are difficult to treat, and molecular targeting is being increasingly considered, but with variable results. This study investigates established and novel molecular-targeted drugs and chemotherapeutic agents for the treatment of PPGLs in human primary cultures and murine cell line spheroids. In PPGLs from 33 patients, including 7 metastatic PPGLs, we identified germline or somatic driver mutations in 79% of cases, allowing us to assess potential differences in drug responsivity between pseudohypoxia-associated cluster 1-related (n = 10) and kinase signaling-associated cluster 2-related (n = 14) PPGL primary cultures. Single anti-cancer drugs were either more effective in cluster 1 (cabozantinib, selpercatinib, and 5-FU) or similarly effective in both clusters (everolimus, sunitinib, alpelisib, trametinib, niraparib, entinostat, gemcitabine, AR-A014418, and high-dose zoledronic acid). High-dose estrogen and low-dose zoledronic acid were the only single substances more effective in cluster 2. Neither cluster 1- nor cluster 2-related patient primary cultures responded to HIF-2a inhibitors, temozolomide, dabrafenib, or octreotide. We showed particular efficacy of targeted combination treatments (cabozantinib/everolimus, alpelisib/everolimus, alpelisib/trametinib) in both clusters, with higher efficacy of some targeted combinations in cluster 2 and overall synergistic effects (cabozantinib/everolimus, alpelisib/trametinib) or synergistic effects in cluster 2 (alpelisib/everolimus). Cabozantinib/everolimus combination therapy, gemcitabine, and high-dose zoledronic acid appear to be promising treatment options with particularly high efficacy in SDHB-mutant and metastatic tumors. In conclusion, only minor differences regarding drug responsivity were found between cluster 1 and cluster 2: some single anti-cancer drugs were more effective in cluster 1 and some targeted combination treatments were more effective in cluster 2.

Purpose The current study investigated whether the changes in patient care in times of the COVID-19 pandemic, especially the reduction of in-person visits, would result in a deterioration of the arrhythmic and clinical condition of patients with an implantable cardioverter defibrillator (ICD) and remote patient monitoring. Methods Data were obtained from a local ICD registry. 140 patients who received ICD implantation at our department and had remote patient monitoring were included. The number of patients with ventricular arrhythmias, appropriate ICD therapy, the number of visits to our outpatient clinic and hospitalization due to acute coronary syndrome, stroke or heart failure were compared during three time intervals of the COVID-19 pandemic (first (LD1) and second (LD2) national lockdown in Germany and the time after the first lockdown (postLD1)) and a time interval 1 year before the pandemic began (preCOV). Each time interval was 49 days long. Results Patients had significantly fewer visits to our outpatient clinic during LD1 (n = 13), postLD1 (n = 22) and LD2 (n = 23) compared to the time interval before the pandemic (n = 43, each p ≤ 0.05). The number of patients with sustained ventricular arrhythmias, appropriate ICD therapy and clinical events showed no significant difference during the time intervals of the COVID-19 pandemic and the time interval 1 year prior. Conclusions The lockdown measures necessary to reduce the risk of infection during the COVID-19 pandemic, led to a reduction of in-person patient visits, but did not result in a deterioration of the arrhythmic and clinical condition of ICD patients with remote patient monitoring.

The various psychological dimensions of professional identity formation (PIF) are an important aspect of the study course for undergraduate medical students. Anatomical learning environments have been repeatedly shown to play a critical role in forming such an identity; however, relevance of PIF during sonoanatomical training remains underexplored. At the end of their basic anatomy studies, third-semester medical students took part in a four-day block course on anatomy and imaging. Anatomical content was revised in small groups using peer teaching and imaging methods, including one hour of hands-on sonoanatomy sessions each day. On-site sonoanatomy was identified as an excellent format to support students' transition from the pre-clinical to clinical phase as medical experts-to-be. Students enjoyed practical exercises and the clinical input, which increased their interest in the medical profession and their academic studies. This study further examined the effects of the transition into an online-only format, necessitated by the current Covid-19 pandemic. A comparison was made between the quantitative and qualitative evaluation data, and the written results of examinations of several on-site (n = 1096, mean age = 22.4 years ± 2.18), and online-only cohorts (n = 230, mean age = 22.6 years ± 2.21). The online-only transition led to a reduction of all PIF-related variables measured, losing identity-related variables, increasing students' stress levels, and reducing their long-term academic performance. Together, this study demonstrates presence of PIF in undergraduate sonoanatomy teaching, and cautions against the uncritical online-only substitution of hands-on learning environments.

There is agreement among health economists that on the whole medical innovation causes health care expenditures (HCE) to rise. This paper analyzes for which diagnoses HCE per patient have grown significantly faster than average HCE. We distinguish decedents (patients in their last 4 years of life) from survivors and use a unique dataset comprising detailed HCE of all members of a regional health insurance fund in Upper Austria for the period 2005–2018. Our results indicate that among decedents in particular, the expenditures for treatment of neoplasms have exceeded the general trend in HCE. This confirms that medical innovation for this group of diseases has been particularly strong over the last 15 years. For survivors, we find a noticeable growth in cases and cost per case for pregnancies and childbirth, and also for treatment of mental and behavioral disorders. We discuss whether these findings contradict the widespread interpretation of cost-increasing innovations as “medical progress” and offer some policy recommendations.

Results from recently completed clinical studies suggest the dopamine D1 receptor positive allosteric modulator (PAM) mevidalen (

Viral infections cause life-threatening disease in immunocompromised patients and especially following transplantation. T cell receptor (TCR) engineering redirects specificity and can bring significant progress to emerging adoptive T cell transfer (ACT) approaches. T cell epitopes are well described, although knowledge is limited on which TCRs mediate protective immunity. In this study, refractory adenovirus (AdV) infection after hematopoietic stem cell transplantation (HSCT) was treated with ACT of highly purified Hexon5-specific T cells using peptide major histocompatibility complex (pMHC)-Streptamers against the immunodominant human leukocyte antigen (HLA)-A∗0101-restricted peptide LTDLGQNLLY. AdV was successfully controlled through this oligoclonal ACT. Novel protective TCRs were isolated ex vivo and preclinically engineered into the TCR locus of allogeneic third-party primary T cells by CRISPR-Cas9-mediated orthotopic TCR replacement. Both TCR knockout and targeted integration of the new TCR in one single engineering step led to physiological expression of the transgenic TCR. Reprogrammed TCR-edited T cells showed strong virus-specific functionality such as cytokine release, effector marker upregulation, and proliferation capacity, as well as cytotoxicity against LTDLGQNLLY-presenting and AdV-infected targets. In conclusion, ex vivo isolated TCRs with clinical proven protection through ACT could be redirected into T cells from naive third-party donors. This approach ensures that transgenic TCRs are protective with potential off-the-shelf use and widened applicability of ACT to various refractory emerging viral infections.

REM sleep without atonia (RSWA) is a key feature for the diagnosis of rapid eye movement (REM) sleep behaviour disorder (RBD). We introduce RBDtector, a novel open-source software to score RSWA according to established SINBAR visual scoring criteria. We assessed muscle activity of the mentalis, flexor digitorum superficialis (FDS), and anterior tibialis (AT) muscles. RSWA was scored manually as tonic, phasic, and any activity by human scorers as well as using RBDtector in 20 subjects. Subsequently, 174 subjects (72 without RBD and 102 with RBD) were analysed with RBDtector to show the algorithm’s applicability. We additionally compared RBDtector estimates to a previously published dataset. RBDtector showed robust conformity with human scorings. The highest congruency was achieved for phasic and any activity of the FDS. Combining mentalis any and FDS any, RBDtector identified RBD subjects with 100% specificity and 96% sensitivity applying a cut-off of 20.6%. Comparable performance was obtained without manual artefact removal. RBD subjects also showed muscle bouts of higher amplitude and longer duration. RBDtector provides estimates of tonic, phasic, and any activity comparable to human scorings. RBDtector, which is freely available, can help identify RBD subjects and provides reliable RSWA metrics.

Contains fulltext : 243898.pdf (Publisher’s version ) (Open Access) OBJECTIVE: There is generally limited but conflicting literature on the incidence, causes, and outcomes of pediatric out-of-hospital cardiac arrest. This study was performed to determine the incidence and outcome of pediatric out-of-hospital cardiac arrest reported by all helicopter emergency medical services in the Netherlands and to provide a description of causes and treatments and, in particular, a description of the specific interventions that can be performed by a physician-staffed helicopter emergency medical service. METHODS: A retrospective analysis was performed of all documented pediatric (0 < 18 years of age) out-of-hospital cardiac arrests from July 2015 to July 2017, attended by all 4 Dutch helicopter emergency medical service teams. RESULTS: Two hundred two out-of-hospital cardiac arrests were identified. The overall incidence in the Netherlands is 3.5 out-of-hospital cardiac arrests in children per 100,000 pediatric inhabitants. The overall survival rate for out-of-hospital cardiac arrest was 11.4%. Eleven (52%) of the survivors were in the drowning group and between 12 and 96 months of age. CONCLUSION: Helicopter emergency medical services are frequently called to pediatric out-of-hospital cardiac arrests in the Netherlands. The survival rate is normal to high compared with other countries. The 12- to 96-month age group and drowning seem to have a relatively favorable outcome.

Purpose of review Acute central and peripheral nervous system injury may occur in association with coronavirus disease 2019 (COVID-19) caused by infection with the severe acute respiratory syndrome coronavirus 2 virus. This review will assist readers to recognize neurologic manifestations associated with COVID-19 including common and life-threatening symptoms and diagnostic testing. We will also review current recommendations for treatment of neurologic injury associated with COVID-19 infection in children. Recent findings Data from systematic reviews and prospectively collected cohorts of children with COVID-19 are beginning to characterize the breadth of neurologic manifestations associated with COVID-19 in the acute infectious and postinfectious periods. Among hospitalized children in particular, neurologic symptoms are common. Life threatening conditions including encephalitis, myelitis, stroke, and demyelinating syndromes have been reported. Within the pediatric population, age, and preexisting neurologic conditions appear to be important factors in determining likely phenotypes. Treatment at this time is based on careful neuromonitoring, supportive care, and neuromodulatory therapies as indicated. Summary Neurologic symptoms are common in children with COVID-19 and may be life threatening. The pathophysiology, therapeutic options, and long-term outcomes from COVID-19 associated neurologic injury are currently being investigated.

Nutrition education through school-based garden programs is a promising intervention to promote youth health and development. Gardeneers is a Chicago-based nonprofit, leading garden programming across area schools. To better understanding their impact on youth health, Gardeneers aimed to define their model more clearly. Using a collective case study design, this mixed-method, formative program evaluation focused on describing program implementation variation across schools. General program design included nutrition education through hands-on garden-based learning. Stakeholder engagement was a strength for some schools and a challenge for others. Sustainability was an ongoing challenge for all schools, particularly funding. Priority student outcomes also varied between schools. Adaptability is core to Gardeneers' approach-the challenge lies in replicable program design and manageable growth, but the strength lies in the ability to meet specific school and student needs. Using these findings, Gardeneers refined their program model and identified program improvements opportunities.

Hematopoietic stem cell (HSC) transplantation is successfully applied since the late 1950s. However, its efficacy can be impaired by insufficient numbers of donor HSCs. A promising strategy to overcome this hurdle is the use of an advanced ex vivo culture system that supports the proliferation and, at the same time, maintains the pluripotency of HSCs. Therefore, we have developed artificial 3D bone marrow-like scaffolds made of polydimethylsiloxane (PDMS) that model the natural HSC niche in vitro. These 3D PDMS scaffolds in combination with an optimized HSC culture medium allow the amplification of high numbers of undifferentiated HSCs. After 14 days in vitro cell culture, we performed transcriptome and proteome analysis. Ingenuity pathway analysis indicated that the 3D PDMS cell culture scaffolds altered PI3K/AKT/mTOR pathways and activated SREBP, HIF1α and FOXO signaling, leading to metabolic adaptations, as judged by ELISA, Western blot and metabolic flux analysis. These molecular signaling pathways can promote the expansion of HSCs and are involved in the maintenance of their pluripotency. Thus, we have shown that the 3D PDMS scaffolds activate key molecular signaling pathways to amplify the numbers of undifferentiated HSCs ex vivo effectively.

A skilled public health workforce is critical to assure the public's health. Recent scholarship has highlighted the benefits of practice-based fieldwork to train the public health workforce. This scholarship has highlighted these benefits primarily through quantitative evaluation. DePaul University's Master of Public Health (MPH) Program provides practice-based education and training to enable students to develop key competencies in public and community health. A key component of the MPH Program is a 9-month practicum experience. This practicum experience requires students to (1) Complete at least 250 h of fieldwork at a local health organization and (2) write a capstone thesis about their practicum project. In this themed issue, seven MPH Program students provide empirical papers, describing their practicum project and the competencies they gained. These empirical papers build upon existing scholarship on practice-based fieldwork and aim to advance academic and community efforts to assure a skilled public and community health workforce.

Purpose/aims The aim of this study was to explore the perceptions that experienced and highly specialized nurses have of the clinical nurse specialist (CNS) role through description of the registered nurses' (RNs') experiences. Design This study used a qualitative descriptive design. Methods Interviews were conducted with 6 RNs (2 managers, 1 chief nursing officer, 2 educators, and 1 clinician) and 32 RNs who participated in 5 focus groups. Participants were purposively sampled from intensive care units and emergency departments from 4 public and private hospitals. The analysis of the narratives and field notes used thematic content analysis. Results Common aspects of the CNS competencies and the experienced RN were recognized. These included direct patient care, assessment, and mentoring, with important differences in management, research, and coaching competencies. Conclusion The findings could facilitate the development of a master's program for the CNS in Chile. Formally recognizing the skills and clinical experiences of expert RNs may motivate nurses to pursue a master's degree that prepares them for advanced practice.

Working in the field of endoscopy is associated with physical and psychological challenges, but we lack data as to whether it influences the health status of endoscopy personnel. The aim of the present survey was to evaluate the health status of endoscopy personnel in Austria and draw comparisons.In 2019, a standardized questionnaire of Hogrefe Publishers and a self-designed SurveyMonkey questionnaire were sent online to doctors (n=326) and nursing staff (n=234) working in the field of gastrointestinal endoscopy in Austria. The response rate was 17.9%. The data were compared with those of a standard population, a similar previous survey from 2004, and national sick leave data.Compared to a standard population of identical age and gender distribution, endoscopy personnel in Austria have more health-related complaints. Compared to doctors, nursing staff experience greater adverse effects; foremost among these are fatigue and an excessive need for sleep (p=0.001), a heavy sensation in the legs (p=0.001), hypersensitivity to warmth (p0.001) and cold (p=0.002). Nursing staff are somewhat more frequently on sick leave than doctors. The days of sick leave were higher than those in 2004, but markedly below the average figures in Austria. Lifestyle had little influence on the respondents' symptoms.The results of the survey showed that persons working in endoscopy have slightly greater health problems than the standard population. Nursing staff are affected more severely than doctors. These data may serve as a basis for targeted preventive measures.Die Arbeit in der Endoskopie ist mit physischen und psychischen Herausforderungen verbunden, es gibt jedoch kaum Daten, ob dadurch die Gesundheit der Betroffenen beeinflusst wird. Ziel der Erhebung war, den Gesundheitszustand von Österreichs Endoskopie-Personal zu evaluieren und Vergleiche anzustellen.2019 wurde an Ärzt*innen (n=236) und Pflegepersonen (n=324) in österreichischen gastrointestinalen Endoskopien ein standardisierter Fragebogen des Hogrefe Verlags und ein selbst entworfener SurveyMonkey Fragebogen online versendet. Die Rücklaufquote betrug 17,9%. Die Daten wurden mit einer Normbevölkerung, mit einer ähnlichen älteren Erhebung aus 2004 und nationalen Krankenstandsdaten verglichen.Im Vergleich mit einer Normbevölkerung gleichen Alters und Geschlechtsverteilung hat österreichisches Endoskopiepersonal mehr gesundheitliche Beschwerden. Im Vergleich mit den Ärzt*innen geben Pflegepersonen mehr Beeinträchtigungen an, am deutlichsten Müdigkeit und übermäßiges Schlafbedürfnis (p=0,001), Schweregefühl in den Beinen (p=0,001) sowie Wärme- (p0,001) und Kälte-Überempfindlichkeit (p=0,002). Pflegepersonen sind etwas häufiger im Krankenstand als Ärzt*innen, die Krankenstandstage haben sich gegenüber 2004 vermehrt, liegen aber deutlich niedriger als im österreichischen Durchschnitt. Lebensstil übt wenig Einfluss auf die Symptome aus.Die Umfrageergebnisse zeigen, dass Arbeiten in der Endoskopie im Vergleich mit der Normbevölkerung mit gering stärkeren gesundheitlichen Problemen einhergeht. Pflegepersonen sind stärker belastet als Ärzt*innen. Diese Daten können Grundlage für gezielte Maßnahmen zur Prävention darstellen.

OBJECTIVES The aim of this study was to explore sex and gender differences regarding aortic events in Marfan patients. METHODS We analysed all data from our connective tissue disorder database. Only patients with Marfan syndrome were included. For analysis, patients were divided by sex. Female patients were further divided into 2 subgroups: with versus without children. Aortic events were defined as Stanford type A aortic dissection (TAAD) or type B aortic dissection (TBAD) or any aortic intervention. RESULTS A population of 183 Marfan patients was analysed for the purpose of this study. One hundred four (57%) were male and 79 (43%) were female patients. Thirty-seven (47%) of the 79 female patients had at least 1 child. Male patients had a significantly higher probability of experiencing an aortic event (P = 0.015) compared to female patients. However, there was no increased probability for recurrent events in male patients compared to female patients (P = 0.063). Follow-up revealed no sex and gender differences in the occurrence of Stanford TAAD or TBAD between male and female patients (P = 0.324/P = 0.534). While 11% of women with children suffered from peripartum aortic events, 24% experienced Stanford TAAD unrelated to pregnancy. CONCLUSIONS Male patients have a higher risk of aortic events than female patients. The majority of women were not aware of their Marfan syndrome diagnosis before conceiving. One out of 10 women suffered from peripartum Stanford TAAD or TBAD. Twice as many female patients with children suffered from aortic dissection unrelated to childbirth. There were no sex and gender differences affecting mortality in Marfan patients.

Despite multiple treatment options, multiple myeloma (MM) remains an incurable disease with poor outcome.We retrospectively analyzed the outcome of MM patients undergoing an allogeneic (allo-SCT; n=34) or autologous stem cell transplantation (auto-SCT; n=41) as salvage treatment for relapsed/refractory (r/r) disease.After a median observation period of 79.9 months in the auto group and 15.7 months in the allo group, the 5- and 10-year OS rates were 54% and 44% in the auto group and 17% and 4% in the allo group (p=0.0002), respectively. The 5- and 10-year disease-free survival in the auto group was 21% and 8%, and 14% and 5% in the allo group (p=0.0142), respectively. The 5- and 10-year cumulative incidence of relapse/progression in the auto group was 69% and 82%, and 64% and 69% in the allo group (p=0.0759), respectively. The 5- and 10-year non-relapse mortality in the auto group was significantly lower than that in the allo group [5% versus 45% (p=0.0001)].A second autotransplant in selected r/r patients offers an acceptable long-term outcome partly because of the significantly lower treatment-related morbidity and mortality.

The objective of the present study on patients with fragility fractures of the sacrum (FFS) was to assess existing risk factors and clinical outcomes after cement sacroplasty (CSP).68 patients (64 women, 4 men) with previous FFS were followed up retrospectively. CT and MRI images were used to classify fractures according to Denis et al. and Rommens and Hofmann. Bone mineral content was determined by QCT in all patients. Concomitant diseases as well as central and peripheral fractures were recorded, considering the patient's medical history and X‑ray images. Vitamin D levels were also determined. If conservative therapy was unsuccessful, CSP was performed. The results were documented on the basis of pain development, physical independence, patient satisfaction, complication rate and mortality.The age of the women in the study was Ø 83.2 (72-99) and that of the men Ø 77.8 (76-85) years. 42.4% had a Denis type 1, 4.2% a Denis type 2, 0% a Denis type 3, 43.3% a Denis type 1-2 and 10.1% a Denis type 1-2-3 fracture zone. FFP type II a to II c fractures were found in 88.2%, FFP type III c in 7.4% and FFP type IV b in 4.4%. Bilateral FFS were found in 68.8%. The average bone mineral content (BMC) was 35.4 (2-74) mg/ml, and the average vitamin D value was 8.8 (0-28) nmol/l. Other osteoporosis-associated fractures were found in around 50% of the patients. After CSP, patients showed a rapid and significant (p 0.001) reduction in pain and sustained clinical improvement.FFS fracture risk factors were found to be female gender, advanced age, existing osteoporosis and severe vitamin‑D deficiency. Patients with non-displaced FFS who could not be mobilised due to pain experienced sustained benefit from CSP.HINTERGRUND: Ziel der Untersuchung bei PatientInnen mit Fragilitätsfrakturen des Os sacrum (FFS) war die Erfassung von vorhandenen Risikofaktoren sowie der klinischen Ergebnisse nach Zementsakroplastie (ZSP).Retrospektiv wurden 68 PatientInnen (64 Frauen, 4 Männer) mit stattgehabten FFS nachuntersucht. Anhand von CT- und MRT-Schnittbildern erfolgte eine Fraktureinteilung nach Denis et al. sowie Rommens und Hofmann. Bei allen PatientInnen wurde eine Knochenmineralgehaltsbestimmung mittels QCT durchgeführt. Unter Berücksichtigung von Anamnese und Röntgenaufnahmen wurden Begleiterkrankungen sowie zentrale und periphere Frakturen miterfasst. Vitamin-D-Werte wurden zusätzlich bestimmt. Nach einem frustranen konservativen Therapieversuch erfolgte eine ZSP. Anhand der Schmerzentwicklung, der körperlichen Selbstständigkeit, der PatientInnen-Zufriedenheit, der Komplikationsrate und der Mortalität wurden die Ergebnisse dokumentiert.Das Alter der Frauen betrugt Ø 83,2 (72–99), dass der Männer Ø 77,8 (76–85) Jahre. Zu 42,4 % fand sich eine Denis-Typ-1-, zu 4,2 % eine Denis-Typ-2-, zu 0 % eine Denis-Typ-3-, zu 43,3 % eine Denis-Typ-1–2- und zu 10,1 % eine Denis-Typ-1–2–3-Frakturzone. Es fand sich ein FFP-Typ-II a-bis -II c-Frakturgeschehen zu 88,2 %, ein FFP-Typ III c zu 7,4 % sowie ein FFP-Typ IV b zu 4,4 %. Bei 68,8 % fanden sich bilaterale FFS. Der Knochenmineralgehalt (KMG) betrug im Ø 35,4 (2–74) mg/ml, der Vitamin-D-Wert im Ø 8,8 (0–28) nmol/l. Weitere osteoporoseassoziierte Frakturen fanden sich in circa 50 %. Nach der ZSP zeigten die PatientInnen eine schnelle und signifikante (p 0,001) Schmerzreduktion sowie nachhaltige klinische Verbesserung.Als Frakturrisikofaktoren von FFS fanden sich das weibliche Geschlecht, das hohe Alter, eine vorhandene Osteoporose und ein schwerer Vitamin-D-Mangel. PatientInnen mit nichtdislozierten FFS, welche schmerzbedingt nicht zu mobilisieren waren, profitierten von einer ZSP nachhaltig.

Purpose: Domestic violence contributes to poor health including sleep disruptions, which has been associated with risk for chronic conditions and ultimately, premature mortality. The present study examined the effects of ever witnessing domestic violence on sleep among urban neighborhoods of color. Design: Cross-sectional. Setting: Ten of Chicago’s 77 community areas. Participants: Adults, aged 18 years and older (N = 1,543, Response Rate = 28.4%). Over 49% of participants reported a Hispanic ethnicity, 34.8 percent reported being non-Hispanic Black and 14.2 percent reported being White. Measures: We used the Sinai Community Health Survey, 2.0, to examine: average hours of sleep in a 24-hour period, ever witnessing domestic violence, ever being emotionally or physically abused, frequent stress in the past 12 months, and other key covariates (race and ethnicity, annual household income, sex, and health status). Analysis: Multivariate logistic regression. Results: In the full model, participants who reported witnessing domestic violence were significantly less likely to report meeting sleep recommendations even after controlling for ever being emotionally or physically abused, frequently feeling stress, demographic factors, and health status. Non-Hispanic Blacks were most likely to report not meeting sleep recommendations (OR = .54, 95% CI = .30-.96, P = .036). Conclusion: Witnessing domestic violence contributes to not meeting sleep recommendations and this appears to be most salient for Non-Hispanic Blacks. These point-in-time findings document an important potential contributor to racial health disparities.

Objectives:Differentiation between post-operative inflammation and bacterial infection remains an important issue in infants following congenital heart surgery. We primarily assessed kinetics and predictive value of C-reactive protein for bacterial infection in the early (days 0–4) and late (days 5–28) period after cardiopulmonary bypass surgery. Secondary objectives were frequency, type, and timing of post-operative infection related to the risk adjustment for congenital heart surgery score.Methods:This 3-year single-centre retrospective cohort study in a paediatric cardiac ICU analysed 191 infants accounting for 235 episodes of CPBP surgery. Primary outcome was kinetics of CRP in the first 28 days after CPBP surgery in infected and non-infected patients.Results:We observed 22 infectious episodes in the early and 34 in the late post-operative period. CRP kinetics in the early post-operative period did not accurately differentiate between infected and non-infected patients. In the late post-operative period, infected infants displayed significantly higher CRP values with a median of 7.91 (1.64–22.02) and 6.92 mg/dl (1.92–19.65) on days 2 and 3 compared to 4.02 (1.99–15.9) and 3.72 mg/dl (1.08–9.72) in the non-infection group. Combining CRP on days 2 and 3 after suspicion of infection revealed a cut-off of 9.47 mg/L with an acceptable predictive accuracy of 76%.Conclusions:In neonates and infants, CRP kinetics is not useful to predict infection in the first 72 hours after CPBP surgery due to the inflammatory response. However, in the late post-operative period, CRP is a valuable adjunctive diagnostic test in conjunction with clinical presentation and microbiological diagnostics.

We investigated severe acute respiratory syndrome coronavirus 2 infections in primary schools, kindergartens, and nurseries in Germany. Of 3,169 oropharyngeal swab specimens, only 2 were positive by real-time reverse transcription PCR. Asymptomatic children attending these institutions do not appear to be driving the pandemic when appropriate infection control measures are used.

In helicopter emergency medical services, HEMS, coagulopathy presents both in trauma (e.g. consumption of coagulation factors) and non-trauma cases (e.g. anticoagulant use). Therefore, in HEMS coagulation measurements appear promising and Prothrombin Time (PT) and derived INR are attractive variables herein. We tested the feasibility of prehospital PT/INR coagulation measurements in HEMS. This study was performed at the Dutch HEMS, using a portable blood analyzer (i-Stat®1, Abbott). PT/INR measurements were performed on (hemodiluted) author's blood, and both trauma- and non-trauma HEMS patients. Device-related benefits of the i-Stat PT/INR system were portability, speed and ease of handling. Limitations included a rather narrow operational temperature range (16–30 °C). PT/INR measurements (n = 15) were performed on hemodiluted blood, and both trauma and non-trauma patients. The PT/INR results confirmed effects of hemodilution and anticoagulation, however, most measurement results were in the normal INR-range (0.9–1.2). We conclude that prehospital PT/INR measurements, although with limitations, are feasible in HEMS operations.

Background: Prompt and precise detection of an infection in the blood is of great clinical importance in terms of early therapy initiation and the patient's prognosis. Infection-triggered inflammatory cellular and humoral signal-ing cascades offer great opportunities to redefine standard tests. However, while inexpensive and easy-to-use bio-markers for the detection of infections and the concomitant inflammatory processes exist, they are rarely used in clinical practice. We aimed to investigate the correlation of Granularity Index (GI) and Delta-hemoglobin equiva-lent (Delta-He) as inexpensive and easy-to-use cell-derived infection markers with established acute-phase param-eters in a randomly selected patient. Methods: We analyzed plasma concentrations of the established C-reactive protein (CRP) and procalcitonin (PCT) and leukocyte and thrombocyte counts in blood samples of 1,787 patients undergoing routine laboratory in-flammation diagnostics. We also measured the Granularity Index (GI) and Delta-hemoglobin equivalent (Delta-He) in this cohort between February 2019 and February 2020. Results: Delta-He and GI Index significantly correlated with CRP concentration (AUC 0.72, 95% CI 0.71 - 0.74; p < 0.001 for both analytes) and thrombocyte count (p < 0.001 for both analytes) but not with leukocyte count (AUC 0.54, 95% CI 0.50 - 0.59, p < 0.67). Furthermore, Delta-He significantly correlated with PCT (AUC 0.65, 95% CI 0.63 - 0.68, p < 0.001) while GI Index did not. Additionally, thrombocyte count significantly correlated with CRP (p < 0.001) and with PCT concentrations (p < 0.001). Conclusions: Delta-He and GI are two novel, inexpensive and easy-to-use cell-derived hematological biomarkers with the potential to be used as fully automated and highly standardized parameters. These biomarkers would be available on a 24 hours basis in the routine laboratory for the detection of bacterial infections by measuring a complete blood count (CBC) with differential and reticulocyte counts.

The coronavirus disease 2019 (COVID-19) pandemic has affected mortality and morbidity across all ages, including children. It is now known that neurological manifestations of COVID-19, ranging from headaches to stroke, may involve the central and/or peripheral nervous system at any age. Neurologic involvement is also noted in the multisystem inflammatory syndrome in children, a pediatric condition that occurs weeks after infection with the causative virus of COVID-19, severe acute respiratory syndrome coronavirus 2. Knowledge about mechanisms of neurologic disease is scarce but rapidly growing. COVID-19 neurologic manifestations may have particularly adverse impacts on the developing brain. Emerging data suggest a cohort of patients with COVID-19 will have longitudinal illness affecting their cognitive, physical, and emotional health, but little is known about the long-term impact on affected children and their families. Pediatric collaboratives have begun to provide important initial information on neuroimaging manifestations and the incidence of ischemic stroke in children with COVID 19. The Global Consortium Study of Neurologic Dysfunction in COVID-19-Pediatrics, a multinational collaborative, is working to improve understanding of the epidemiology, mechanisms of neurological manifestations, and the long-term implications of COVID-19 in children and their families.

T cell receptor (TCR) avidity is assumed to be a major determinant of the spatiotemporal fate and protective capacity of tumor-specific T cells. However, monitoring polyclonal T cell responses with known TCR avidities in vivo over space and time remains challenging. Here, we investigated the fate and functionality of tumor neoantigen–specific T cells with TCRs of distinct avidities in a well-established, reductionist preclinical tumor model and human patients with melanoma. To this end, we used polyclonal T cell transfers with in-depth characterized TCRs together with flow cytometric phenotyping in mice inoculated with MC38 OVA tumors. Transfer of T cells from retrogenic mice harboring TCRs with high avidity resulted in best tumor protection. Unexpectedly, we found that both high- and low-avidity T cells are similarly abundant within the tumor and adopt concordant phenotypic signs of exhaustion. Outside the tumor, high-avidity TCR T cells were not generally overrepresented but, instead, selectively enriched in T cell populations with intermediate PD-1 protein expression. Single-cell sequencing of neoantigen-specific T cells from two patients with melanoma—combined with transgenic reexpression of identified TCRs by CRISPR-Cas9–mediated orthotopic TCR replacement—revealed high-functionality TCRs to be enriched in T cells with RNA signatures of recent activation. Furthermore, of 130 surface protein candidates, PD-1 surface expression was most consistently enriched in functional TCRs. Together, our findings show that tumor-reactive TCRs with high protective capacity circulating in peripheral blood are characterized by a signature of recent activation.

CDK4/6 inhibitors (CDK4/6i) and oncolytic viruses are promising therapeutic agents for the treatment of various cancers. As single agents, CDK4/6 inhibitors that are approved for the treatment of breast cancer in combination with endocrine therapy cause G1 cell cycle arrest, whereas adenoviruses induce progression into S-phase in infected cells as an integral part of the their life cycle. Both CDK4/6 inhibitors and adenovirus replication target the Retinoblastoma protein albeit for different purposes. Here we show that in combination CDK4/6 inhibitors potentiate the anti-tumor effect of the oncolytic adenovirus XVir-N-31 in bladder cancer and murine Ewing sarcoma xenograft models. This increase in oncolytic potency correlates with an increase in virus-producing cancer cells, enhanced viral genome replication, particle formation and consequently cancer cell killing. The molecular mechanism that regulates this response is fundamentally based on the reduction of Retinoblastoma protein expression levels by CDK4/6 inhibitors.

Numerous patient-related clinical parameters and treatment-specific variables have been identified as causing or contributing to the severity of peritonitis. We postulated that a combination of clinical and surgical markers and scoring systems would outperform each of these predictors in isolation. To investigate this hypothesis, we developed a multivariable model to examine whether survival outcome can reliably be predicted in peritonitis patients treated with open abdomen. This single-center retrospective analysis used univariable and multivariable logistic regression modeling in combination with repeated random sub-sampling validation to examine the predictive capabilities of domain-specific predictors (i.e., demography, physiology, surgery). We analyzed data of 1,351 consecutive adult patients (55.7% male) who underwent open abdominal surgery in the study period (January 1998 to December 2018). Core variables included demographics, clinical scores, surgical indices and indicators of organ dysfunction, peritonitis index, incision type, fascia closure, wound healing, and fascial dehiscence. Postoperative complications were also added when available. A multidomain peritonitis prediction model (MPPM) was constructed to bridge the mortality predictions from individual domains (demographic, physiological and surgical). The MPPM is based on data of n = 597 patients, features high predictive capabilities (area under the receiver operating curve: 0.87 (0.85 to 0.90, 95% CI)) and is well calibrated. The surgical predictor “skin closure” was found to be the most important predictor of survival in our cohort, closely followed by the two physiological predictors SAPS-II and MPI. Marginal effects plots highlight the effect of individual outcomes on the prediction of survival outcome in patients undergoing staged laparotomies for treatment of peritonitis. Although most single indices exhibited moderate performance, we observed that the predictive performance was markedly increased when an integrative prediction model was applied. Our proposed MPPM integrative prediction model may outperform the predictive power of current models.

University students occupy a socially marginal position and therefore are often underserved by academic and service institutions. This article analyzes food and housing security among students at The University of Texas at El Paso, a Hispanic-Serving Institution located in the U.S.-Mexico Border region. Findings of a sample of n = 7,633 university students are presented in the first cross-sectional, two-year food and housing security study on campus administered via platform Campus Labs Baseline. The first sample in 2019 consisted of n = 2,615 students representing 10.4% of student enrollment (25,177 total 2019 enrollment), and the second sample in 2020 was n = 5,018 representing 20.2% of student enrollment (24,879 total 2020 enrollment). To measure food security, the six-item short form of the U.S. Department of Agriculture (USDA) Household Food Security Survey Module was used. To document housing security, we created questions informed by student input. In this study, survey results are reported, and tests are conducted to assess the relationships between various student characteristics and food and housing security. Student characteristics significantly impacting food and housing security are probed further using data visualizations and subpopulation analysis with a focus on analyzing factors impacted by the COVID-19 pandemic. Results indicate that employment status, consistent employment status, hours per week, academic level, number of dependents, and gender are all factors associated with food security during the pandemic but not prior to the pandemic. Other factors, including, college affiliation, ethnicity/race, having any dependents and being head of household, living alone, mode of campus transportation and mode of the transportation, household income, and age, all were associated with food security in both academic years. Using these results, a critical analysis of past interventions addressing food and housing security is presented with a focus on changes made during the pandemic. Recommendations are made for further data-driven interventions and future steps.

The aim of this study is to provide a more accurate representation of COVID-19's case fatality rate (CFR) by performing meta-analyses by continents and income, and by comparing the result with pooled estimates. We used multiple worldwide data sources on COVID-19 for every country reporting COVID-19 cases. On the basis of data, we performed random and fixed meta-analyses for CFR of COVID-19 by continents and income according to each individual calendar date. CFR was estimated based on the different geographical regions and levels of income using three models: pooled estimates, fixed- and random-model. In Asia, all three types of CFR initially remained approximately between 2.0% and 3.0%. In the case of pooled estimates and the fixed model results, CFR increased to 4.0%, by then gradually decreasing, while in the case of random-model, CFR remained under 2.0%. Similarly, in Europe, initially, the two types of CFR peaked at 9.0% and 10.0%, respectively. The random-model results showed an increase near 5.0%. In high-income countries, pooled estimates and fixed-model showed gradually increasing trends with a final pooled estimates and random-model reached about 8.0% and 4.0%, respectively. In middle-income, the pooled estimates and fixed-model have gradually increased reaching up to 4.5%. in low-income countries, CFRs remained similar between 1.5% and 3.0%. Our study emphasizes that COVID-19 CFR is not a fixed or static value. Rather, it is a dynamic estimate that changes with time, population, socioeconomic factors, and the mitigatory efforts of individual countries.

OBJECTIVES This study was performed to determine the clinical and haemodynamic variables associated with early adverse outcomes after the neonatal Norwood procedure. METHODS Patients who underwent the neonatal Norwood procedure between 2001 and 2019 were included. The patient diagnosis, morphological characteristics and haemodynamic parameters were analysed to identify factors associated with length of stay (LOS) in the intensive care unit (ICU) and mortality during the stay. RESULTS A total of 322 patients were depicted. The median age and weight at the Norwood procedure were 9 days and 3.2 kg, respectively. Certain morphological and preoperative parameters, such as birth weight below 2.5 kg, restrictive atrial septal defect, extracardiac anomalies and the diameter of the ascending aorta, were found to be associated with the LOS in the ICU. Analysis using early postoperative haemodynamic variables revealed that systolic arterial pressure, diastolic arterial pressure, serum lactate levels and reduced ventricular function at 2 days postoperatively were associated with the LOS in the ICU. Birth weight CONCLUSIONS The LOS in the ICU after the Norwood procedure was predicted by early postoperative haemodynamic variables, suggesting that good early postoperative haemodynamics determine early recovery. A prolonged stay in the ICU after the Norwood procedure was associated with late mortality.

© 2021 The Authors., The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers., Hyun-Dong Chang is supported by the Dr. Rolf M. Schwiete Foundation. Susanne Melzer and Attila Tarnok thank De Novo Software for providing FCS Express. Enrico Lugli is supported by a grant from the Associazione Italiana per la Ricerca sul Cancro (AIRC IG20676). Gabriele De Simone and Giovanni Galletti were supported by Fellowships from the Fondazione Italiana per la Ricerca sul Cancro-Associazione Italiana per la Ricerca sul Cancro (FIRC-AIRC). Jun Dong is supported by Deutsche Forschungsgemeinschft (DFG, German Research Foundation) Projektnummer 389687267 and Chinesisch-Deutsches Zentrum für Wissenschaftsförderung [Sino-German Center for Research Promotion (SGC)] grant C-0072. Nicola Gagliani, Samuel Huber and Franziska Muscate are supported by DFG fundings: SFB841,GA 2441/3-1, HU 1714/10-1. The tetramer APC-conjugated H-2K (d) HIV-1 gag197-205 AMQMLKETI used in TDS assay for mouse blood T cells was obtained through the NIH Tetramer Facility. Larissa Nogueira Almeida was supported by DFG research grant MA 2273/14-1. Supported by the following grants: AIRC 5X1000 2018 id. 21147 (Lorenzo Moretta); AIRC IG 2017 id. 19920 (Lorenzo Moretta); RC-2020 OPBG (Lorenzo Moretta); AIRC and European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 800924 (Linda Quatrini). Dirk Baumjohann was supported by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Emmy Noether Programme BA 5132/1-2 (252623821) and Germany's Excellence Strategy EXC2151 (390873048).

The COVID-19 pandemic has affected mortality and morbidity across all ages, including children. Neurologic manifestations of coronavirus disease 2019, ranging from headaches to cerebrovascular stroke, may involve the CNS or peripheral nervous system. Neurologic involvement is also noted in the multisystem inflammatory syndrome in children, a pediatric condition that occurs weeks after infection with severe acute respiratory syndrome coronavirus 2, the virus that causes COVID-19. Knowledge about mechanisms of neurologic disease and immunologic response to severe acute respiratory syndrome coronavirus 2 is scarce but rapidly growing. Here, we concisely review experimental and clinical data relevant to pathophysiologic hypotheses regarding neurologic manifestations of coronavirus disease 2019. We highlight important knowledge gaps in differences between adults and children in their response to coronavirus disease 2019.

Purpose To compare performance data of adolescents collected with five different bicycle spiroergometry protocols and to assess the necessity for establishing standard values for each protocol. Methods One-hundred-twenty adolescents completed two bicycle spiroergometries within 14 days. One of the two tests was performed based on our institutional weight-adapted protocol (P0). The other test was performed based on one out of four exercise protocols widely used for children and adolescents (P1, 2, 3 or 4) with 30 persons each. The two tests were performed in a random order. Routine parameters of cardiopulmonary exercise tests (CPET) such as VO2peak, maximum power, O2 pulse, OUES, VE/VCO2 slope as well as ventilatory and lactate thresholds were investigated. Agreement between protocols was evaluated by Bland–Altman analysis, coefficients of variation (CV) and intra-class correlation coefficients (ICC). Results None of the CPET parameters were significantly different between P0 and P1, 2, 3 or 4. For most of the parameters, low biases between P0 and P1–P4 were found and 95% confidence intervalls were narrow. CV and ICC values largely corresponded to well-defined analytical goals (CV 0.9). Only maximal power (Pmax) showed differences in size and drift of the bias depending on the length of the step duration of the protocols. Conclusion Comparability between examination protocols has been shown for CPET parameters independent on step duration. Protocol-dependent standard values do not appear to be necessary. Only Pmax is dependent on the step duration, but in most cases, this has no significant influence on the fitness assessment.

Background Aim of the study was a better characterization of heart failure (HF) with recovered ejection fraction (HFrecEF) and undulating EF (HFuEF) with regard to re-hospitalization due to congestive HF (CHF), adequate electric therapies (AETs) and mortality compared to HF with reduced EF (HFrEF), mid-range EF (HFmrEF) and preserved EF (pEF). Methods Retrospective study of 342 participants with an implantable cardioverter defibrillator (ICD) for primary or secondary prevention. Type of HF was classified according to left ventricular EF with 4.7 ± 3.1 investigations for each patient. Results Re-hospitalization due to CHF was similar in HFrecEF (7 (9.5%)), HFmrEF (2(9.0%)) and pEF (8(12.9%); p = n.s.) and significantly higher in HFrEF (62(38.0%)) and HFuEF (6(28.6%); p < .001 compared to HFrecEF and HFrEF). AETs were significantly lower in HFrecEF (13(17.6%)) compared to HFrEF (57(35.0%)), HFmrEF (7(31.8%)), pEF (18(29.0%)) and HFuEF (6(28.6%); each p < .01 compared to HFrecEF). Mortality was similar in HFrecEF (6(8.1%)) compared to HFuEF (0(0%)), pEF (4(6.5%)) and HFmrEF (2(9.0%), p = n.s.) and significantly lower compared to HFrEF (52(31.9%), p < .001). HFrEF was the strongest predictor for mortality besides age and chronic renal insufficiency according to Cox Regression (each p < .05) opposite to arterial hypertension, diabetes, type of cardiomyopathy and secondary prevention ICD indication (each p = n.s.). Conclusions HFrecEF indicates as a new entity of HF with similar prognosis as pEF and HFmrEF with regard to re-hospitalization due to CHF and mortality and even better prognosis with regard to AETs. HFuEF showed similar rates of re-hospitalization due to CHF and AETs compared to HFrEF, but lower rates of mortality.

Background Fragility fractures of the sacrum (FFS) have been detected more and more frequently in recent times, and the incidence will continue to increase due to increasing life expectancy. The aim of this study was to compare the clinical outcome of conservative, interventional and surgical treatment of FFS. Methods Retrospectively, 292 patients (276 women, 16 men) with confirmed FFS were followed up over a period of 2 years. The age of the women was Ø 81.2 (58 - 99) and that of the men Ø 78.1 (76 - 85) years. The pain was quantified using a VAS. Fractures were classified in accordance with the Rommens and Hofmann and with the Denis classification using conventional X-rays, CT and MRI. A QCT of the lumbar spine was performed to quantify bone mineral density. Concomitant diseases of every patient were recorded. An interdisciplinary case conference determined the individual treatment concept considering the age, type of fracture, pain level and comorbidities with classification into conservative, interventional (any type of sacroplasty) or surgical treatment. Over the course pain and independence were measured, complications and patient satisfaction were documented. A vitamin D determination was done, and existing comorbidities were included. Results Patients with a pain level of ≤5 benefited from the conservative therapy measures, with pain levels > 5 significantly delaying the development of mobility. After sacroplasty, the pain reduced significantly, which caused a rapid improvement in mobility without any significant difference being found between vertebro- (VSP), balloon (BSP), radiofrequency (RFS) and cement sacroplasty (CSP). In terms of pain reduction and mobilization, the surgical treated patients benefited from osteosynthesis, although more complex fracture types with lumbopelvic stabilization took longer. Overall, there were no deaths during the hospital stay. Mortality after 12 months was 21.7% for the conservative, 8.4% for the interventional and 13.6% for the surgical therapy group; the differences are significant. For patients in the conservative therapy group who were difficult to mobilize due to pain, the mortality increased to 24.3%. Over 24 months, patients achieved the best independence after sacroplasty. At 12 and 24 months, subjective satisfaction with the therapies was best after sacroplasty, followed by osteosynthesis and conservative measures. All patients had a pronounced vitamin D deficiency and manifest osteoporosis. Cardiovascular pathologies were the main concomitant diseases. Conclusions Patients with FFS with a low level of pain benefit from conservative therapy measures, whereby complications and mortality increase significantly in the case of persistent immobilizing pain. Patients with an unacceptable level of pain resulting from non-dislocated fractures benefit significantly from sacroplasty. Patients with unstable and displaced fractures (Rommens and Hofmann type III and IV) should be operated on promptly. Different techniques are available for sacroplasty and osteosynthesis, which lead to an improvement of independence and a reduction in mortality.

BACKGROUND: Resistance training and protein supplementation are recommended strategies to combat sarcopenia. AIM: Quantification of muscle thickness (MT) by musculoskeletal ultrasound is a promising method to follow changes in skeletal muscles. The aim of this study was to investigate the effect of six months of resistance training with or without nutritional supplementation on MT of M. quadriceps in institutionalized old adults. DESIGN: This is a prospective, randomized, multi-arm parallel and controlled intervention study. SETTING: This study was conducted in five different retirement care facilities. POPULATION: Institutionalized individuals (mean age 82.6±6.2 years) were randomly assigned to an elastic band resistance training (N.=41), training with nutritional supplementation (N.=36) or control group (N.=40). METHODS: Health status and handgrip strength were investigated at baseline. MT of all parts of M. quadriceps of the left leg was assessed using musculoskeletal ultrasound at baseline and after six months. Linear regression models adjusted for age, BMI and sex were calculated to investigate the influence of baseline characteristics on MT. Multivariable regression analyses were performed for investigation of study intervention on MT. Follow-up examinations were performed after 12 and 18 months. RESULTS: Handgrip strength of both hands was significantly correlated with MT of M. vastus lateralis. Moreover, the sum of regularly taken medication was significantly correlated to MT of all parts of quadriceps. Six months of training or nutritional supplementation was not able to alter MT. However, participants with lower baseline MT values or a higher number of diseases and medications at baseline showed significant higher increases in MT after intervention. CONCLUSIONS: Resistance training using elastic bands with or without nutritional supplementation did not alter MT of M. quadriceps of old institutionalized individuals. However, baseline values and health status had a significant influence on the training effect. CLINICAL REHABILITATION IMPACT: As old individuals are very heterogenic according to their health and muscle status; further studies might focus on individualizing training regimes with particular emphasize on accompanied diseases and medications of this population.