The prevalence of immunoglobulin E (IgE)-mediated allergic diseases is currently experiencing an epidemic trend characterized by an increase in both the number of affected individuals and the proportion of patients with multiple sensitizations. The majority of these multiple sensitizations are attributed to IgE reactions to genuine allergenic proteins from unrelated species. However, there is a growing trend of patients becoming sensitized to highly cross-reactive molecules, such as profilins, polcalcins, lipocalins, serum albumins, tropomyosins, and non-specific lipid transfer proteins (nsLTPs). In addition, allergen families that were previously considered of minimal importance are now gaining recognition for their role in the pathogenesis of IgE-mediated allergic diseases. Consequently, these allergen families are increasingly being considered in the diagnostic process. In this review, we aim to provide a comprehensive summary of the biochemical and allergological information about two of these “new” allergen families: cyclophilins (Cyp) and gibberellin-regulated proteins (GRP).

Background: Nurses working in long-term care facilities were vaccinated first before residents as a matter of priority to protect the latter. Although the vaccination rate of nursing staff eventually rose due to a facility-based vaccination requirement, studies on associated factors of vaccination status are currently not available for the long-term care setting in Germany.Objective: Associated factors of COVID-19 vaccination status among nursing staff in long-term care facilities were explored.Methods: An online survey was conducted between October 26th 2021 and January 31st 2022. A total of 1546 nurses working in long-term care in Germany responded to questions concerning the Covid-19 vaccination campaign. Logistic regression analyses were performed.Results: In this study 8 out of 10 nurses were vaccinated against COVID-19 (80.6%). Approximately 7 out of 10 nurses thought at least a few times about quitting their job since the pandemic began (71.4%). A positive COVID-19 vaccination status was associated with older age, full-time employment, COVID-19 deaths at the facility and working in northern or western Germany. Frequent thoughts of quitting their job were associated with negative COVID-19 vaccination status.Conclusion: The present findings provide evidence on factors associated with the COVID-19 vaccination status of nurses in long-term care facilities in Germany for the first time. Further quantitative as well as qualitative studies are necessary for a more comprehensive understanding of the COVID-19 vaccination decision-making among nurses in long-term care, in order to implement target-oriented future vaccination campaigns in this care setting.

Introduction While large progress has been achieved in identifying and treating the most common pathogens involved in periprosthetic joint infections (PJI), there remains limited knowledge on atypical pathogens such as Corynebacterium. For that reason, we analyzed infection and diagnostical characteristics, as well as treatment outcome in Corynebacterium PJI.Methods A systematic review was performed based on a structured PubMed and Cochrane Library analysis using the PRISMA algorithm. The search was performed by 2 independent reviewers, and articles from 1960 to 2022 considered eligible for inclusion. Out of 370 search results, 12 studies were included for study synthesis.Results In total, 52 cases of Corynebacterium PJI were identified (31 knees, 16 hips, 4 elbows, 1 shoulder). Mean age was 65 years, with 53% females, and a mean Charlson Comorbidity Index of 3.9. The most common species was Corynebacterium striatum in 37 cases (71%). Most patients were treated with two-stage exchange (40%), isolated irrigation and debridement (21%), and resection arthroplasty (19%). Mean duration of antibiotic treatment was 8.5 weeks. At a mean follow-up of 2.5 years, there were 18 reinfections (33%), and 39% were for Corynebacterium. Initial infection by Corynebacterium striatum species was predictive of reoperation (p = 0.035) and reinfection (p = 0.07).Conclusion Corynebacterium PJI affects multimorbid and elderly patients, with one in three developing a reinfection at short term. Importantly, the relative majority of reinfections was for persistent Corynebacterium PJI.

Objective: Bilaterally absent cortical somatosensory evoked potentials (SSEPs) reliably predict poor outcome in comatose cardiac arrest (CA) patients. Cortical SSEP amplitudes are a recent prognostic extension; however, amplitude thresholds, inter-recording, and inter-rater agreement remain uncertain.Methods: In a retrospective multicenter cohort study, we determined cortical SSEP amplitudes of comatose CA patients using a standardized evaluation pathway. We studied inter-recording agreement in repeated SSEPs and inter-rater agreement by four raters independently determining 100 cortical SSEP amplitudes. Primary outcome was assessed using the cerebral performance category (CPC) upon intensive care unit discharge dichotomized into good (CPC 1-3) and poor outcome (CPC 4-5).Results: Of 706 patients with SSEPs with median 3 days after CA, 277 (39.2%) had good and 429 (60.8%) poor outcome. Of patients with bilaterally absent cortical SSEPs, one (0.8%) survived with CPC 3 and 130 (99.2%) had poor outcome. Otherwise, the lowest cortical SSEP amplitude in good outcome patients was 0.5 & mu;V. 184 (42.9%) of 429 poor outcome patients had lower cortical SSEP amplitudes. In 106 repeated SSEPs, there were 6 (5.7%) with prognostication-relevant changes in SSEP categories. Following a standardized evaluation pathway, inter-rater agreement was almost perfect with a Fleiss' kappa of 0.88.Interpretation: Bilaterally absent and cortical SSEP amplitudes below 0.5 & mu;V predicted poor outcome with high specificity. A standardized evaluation pathway provided high inter-rater and inter-recording agreement. Regain of consciousness in patients with bilaterally absent cortical SSEPs rarely occurs. High-amplitude cortical SSEP amplitudes likely indicate the absence of severe brain injury.

Early research suggested that compulsive sexual behavior (CSB) and paraphilic interests (PI) are more prevalent in adults with primary tic disorders compared to the general population. However, recent data on this topic remain scarce. We conducted an anonymous online survey capturing data on CSB and PI in adult patients with primary tic disorders. We also explored the role of antipsychotic tic medication and the impact of neuropsychiatric comorbidities like attention-deficit hyperactivity disorder and depression. In total, 62 participants (26 females/36 males) completed the survey. The prevalence of CSB and PI were 12.9% and 19.4%, respectively. There was no association with antipsychotic medication nor with symptoms of depression. However, the presence of attention-deficit hyperactivity disorder was associated with a higher prevalence of both CSB and PI. The current results contrast with earlier reports and show that in adults with primary tic disorders, the prevalence of CSB and PI is not overly prominent.

Introduction Reversible cerebral vasoconstriction syndrome (RCVS) has a heterogenous clinical and radiological presentation. We investigated whether RCVS complications vary according to age.Patients and methods In a pooled French cohort of 345 patients with RCVS, we assessed (1) rates of clinical and radiological complications, and (2) the functional outcome at 3 months according to age as a continuous variable, and in young patients aged <= 49 years versus those aged >= 50 years. The Commission Nationale Informatique et Liberte and the local ethics committee approved this study (registration number: 202100733).Results The risk for any focal deficit and for any brain lesion were independently associated with increasing age (OR 1.4, 95% CI 1.1-1.8; p = 0.014, and OR 1.6, 95% CI 1.2-2.1; p < 0.001, respectively). Subtypes of brain lesions independently associated with increasing age were subarachnoid haemorrhage (OR 1.7, 95% CI 1.3-2.3; p < 0.001) and intracerebral haemorrhage (OR 1.5, 95% CI 1.1-2.2; p = 0.023). Frequency of cervical artery dissections peaked at age 30-39, and young age was independently associated with cervical artery dissections (OR 13.6, 95% CI 2.4-76.6; p = 0.003). Age had no impact on the functional outcome, with a modified Rankin scale score of 0-1 in > 96% of patients.Conclusion Age seems to influence rates and types of complications of RCVS, with young age being associated with cervical artery dissections, and increasing age with haemorrhagic complications. If confirmed in larger prospective studies, recognition of age-specific patterns might help to guide clinical management and to identify complications in cases of RCVS and vice versa.

Objectives The analysis of myocardial deformation using feature tracking in cardiovascular MR allows for the assessment of global and segmental strain values. The aim of this study was to compare strain values derived from artificial intelligence (AI)-based contours with manually derived strain values in healthy volunteers and patients with cardiac pathologies.Materials and methods A cohort of 136 subjects (60 healthy volunteers and 76 patients; of those including 46 cases with left ventricular hypertrophy (LVH) of varying etiology and 30 cases with chronic myocardial infarction) was analyzed. Comparisons were based on quantitative strain analysis and on a geometric level by the Dice similarity coefficient (DSC) of the segmentations. Strain quantification was performed in 3 long-axis slices and short-axis (SAX) stack with epi- and endocardial contours in end-diastole. AI contours were checked for plausibility and potential errors in the tracking algorithm.Results AI-derived strain values overestimated radial strain (+ 1.8 & PLUSMN; 1.7% (mean difference & PLUSMN; standard deviation); p = 0.03) and underestimated circumferential (- 0.8 & PLUSMN; 0.8%; p = 0.02) and longitudinal strain (- 0.1 & PLUSMN; 0.8%; p = 0.54). Pairwise group comparisons revealed no significant differences for global strain. The DSC showed good agreement for healthy volunteers (85.3 & PLUSMN; 10.3% for SAX) and patients (80.8 & PLUSMN; 9.6% for SAX). In 27 cases (27/76; 35.5%), a tracking error was found, predominantly (24/27; 88.9%) in the LVH group and 22 of those (22/27; 81.5%) at the insertion of the papillary muscle in lateral segments.Conclusions Strain analysis based on AI-segmented images shows good results in healthy volunteers and in most of the patient groups. Hypertrophied ventricles remain a challenge for contouring and feature tracking.

Objectives Coronary computed tomography angiography (CCTA) has higher diagnostic accuracy than coronary artery calcium (CAC) score for detecting obstructive coronary artery disease (CAD) in patients with stable chest pain, while the added diagnostic value of combining CCTA with CAC is unknown. We investigated whether combining coronary CCTA with CAC score can improve the diagnosis of obstructive CAD compared with CCTA alone. Methods A total of 2315 patients (858 women, 37%) aged 61.110.2 from 29 original studies were included to build two CAD prediction models based on either CCTA alone or CCTA combined with the CAC score. CAD was defined as at least 50% coronary diameter stenosis on invasive coronary angiography. Models were built by using generalized linear mixed-effects models with a random intercept set for the original study. The two CAD prediction models were compared by the likelihood ratio test, while their diagnostic performance was compared using the area under the receiver-operating-characteristic curve (AUC). Net benefit (benefit of true positive versus harm of false positive) was assessed by decision curve analysis. Results CAD prevalence was 43.5% (1007/2315). Combining CCTA with CAC improved CAD diagnosis compared with CCTA alone (AUC: 87% [95% CI: 86 to 89%] vs. 80% [95% CI: 78 to 82%]; p<0.001), likelihood ratio test 236.3, df: 1, p<0.001, showing a higher net benefit across almost all threshold probabilities. Conclusion Adding the CAC score to CCTA findings in patients with stable chest pain improves the diagnostic performance in detecting CAD and the net benefit compared with CCTA alone.

Primary Immune thrombocytopenia (ITP) is an autoimmune disease. Secondary ITP occurs in patients with underlying diseases such as common variable immunodeficiency (CVID). CVID is one of the most common symptomatic primary immunodeficiencies in adults, characterised by infectious and non-infectious symptoms. Amongst CVID patients, ITP is the most frequent autoimmune manifestation. In this single-centre study, we performed a clinical and immunological characterisation of 20 patients with CVID-related ITP and 20 ITP patients without CVID to compare severity and remission rates. We found that patients with CVID-related ITP had a higher WHO Bleeding Scale at initial diagnosis yet showed higher remission rates and required less treatment. Patients with ITP needed up to seven therapy options and were often treated with second-line drug therapy, whilst only one CVID-related ITP patient required second-line drug therapy. Therefore, we show that the course of thrombocytopenia in patients with CVID-related ITP is milder. Furthermore, we show that soluble interleukin-2 receptor (sIL-2R, CD25) was higher in CVID-related ITP compared to ITP patients and could accurately classify patient cohorts with an Area Under the Receiver Operating Characteristic of 0.92. Whilst none of the ITP patients had a history of immunodeficiency, we found immunological abnormalities in 12 out of 18 patients. Therefore, we recommend screening ITP patients for CVID and other immunodeficiencies to detect immune abnormalities early, as we found patients with reduced immunoglobulin levels as well as severe lymphocytopenia in our ITP cohort.

Background Information on cerebrospinal fluid (CSF) findings in patients with neurological manifestations in post-COVID-19 syndrome is scarce.Methods Retrospective evaluation of 84 CSF samples in patients fulfilling post-COVID-19 criteria in two neurological post-COVID-19 outpatient clinics.Results In 68% of samples, all CSF parameters were normal. The most frequent pathological CSF finding was elevation of total protein (median total protein 33.3 mg/dl [total range 18.5-116.2]) in 20 of 83 (24%) samples. The second most prevalent pathological finding was a blood-CSF barrier dysfunction as measured by elevation of QAlb (median QAlb 4.65 [2.4-13.2]) in 11/84 (13%). Pleocytosis was found in only 5/84 (6%) samples and was mild in all of them. CSF-restricted oligoclonal bands were found in 5/83 (6%) samples. Anti-neuronal autoantibodies in CSF were negative in most cases, whilst 12/68 (18%) samples were positive for anti-myelin autoantibodies in serum. PCR for herpesviridae (HSV-1/-2, VZV, EBV, CMV, HHV6) showed, if at all, only weakly positive results in CSF or EDTA whole blood/plasma.Conclusions The majority of samples did not show any pathologies. The most frequent findings were elevation of total protein and blood-CSF barrier dysfunction with no signs of intrathecal inflammation. CSF analysis still keeps its value for exclusion of differential diagnoses.

Purpose: Cardiac radioablation (cRA) using a stereotactic single-session radioablative approach has recently been described as a possible treatment option for patients with otherwise untreatable recurrent ventricular tachycardia (VT). There is very limited experience in cRA for patients undergoing left ventricular assist device (LVAD) therapy. We present clinical experiences of two patients treated with cRA for incessant VT under long-term LVAD therapy.Methods: Two male patients (54 and 61 years old) with terminal heart failure under LVAD therapy (both patients for 8 years) showed incessant VT despite extensive antiarrhythmic drug therapy and repeated catheter ablation. cRA with a single dose of 25 Gy was applied as a last resort strategy under compassionate use in both patients following an electroanatomical mapping procedure.Results: Both patients displayed ongoing VT during and after the cRA procedure. Repeated attempts at post-procedural rhythm conversion failed in both patients; however, one patient was hemodynamically stabilized and could be discharged home for several months before falling prey to a fatal bleeding complication. The second patient initially stabilized for a few days following cRA before renewed acceleration of running VT required bilateral ablation of the stellate ganglion; the patient died 50 days later. No immediate side effects of cRA were detected in either patient.Conclusion: cRA might serve as a last resort strategy for patients with terminal heart failure undergoing LVAD therapy and displaying incessant VT. Intermediate- and long-term outcomes of these seriously ill patients often remain poor; therefore, best supportive care strategies should also be evaluated as long as no clear beneficial effects of cRA procedures can be shown. For patients treated with cRA under running ventricular rhythm abnormality, strategies for post-procedural generation of stabilized rhythm have to be established.

Objectives Knowledge of Candida spondylodiscitis is limited to case reports and smaller case series. Controversy remains on the most effective diagnostical and therapeutical steps once Candida is suspected. This systematic review summarized all cases of Candida spondylodiscitis reported to date concerning baseline demographics, symptoms, treatment, and prognostic factors.Methods A PRISMA-based search of PubMed, Web of Science, Embase, Scopus, and OVID Medline was performed from database inception to November 30, 2022. Reported cases of Candida spondylodiscitis were included regardless of Candida strain or spinal levels involved. Based on these criteria, 656 studies were analyzed and 72 included for analysis. Kaplan-Meier curves, Fisher's exact, and Wilcoxon's rank sum tests were performed.Results In total, 89 patients (67% males) treated for Candida spondylodiscitis were included. Median age was 61 years, 23% were immunocompromised, and 15% IV drug users. Median length of antifungal treatment was six months, and fluconazole (68%) most commonly used. Thirteen percent underwent debridement, 34% discectomy with and 21% without additional instrumentation. Median follow-up was 12 months. The two year survivorship free of death was 80%. The two year survivorship free of revision was 94%. Younger age (p = 0.042) and longer length of antifungal treatment (p = 0.061) were predictive of survival.Conclusion Most patients affected by Candida spondylodiscitis were males in their sixties, with one in four being immunocompromised. While one in five patients died within two years of diagnosis, younger age and prolonged antifungal treatment might play a protective role.

FINCA syndrome [MIM: 618278] is an autosomal recessive multisystem disorder characterized by fibrosis, neurodegeneration and cerebral angiomatosis. To date, 13 patients from nine families with biallelic NHLRC2 variants have been published. In all of them, the recurrent missense variant p.(Asp148Tyr) was detected on at least one allele. Common manifestations included lung or muscle fibrosis, respiratory distress, developmental delay, neuromuscular symptoms and seizures often followed by early death due to rapid disease progression.Here, we present 15 individuals from 12 families with an overlapping phenotype associated with nine novel NHLRC2 variants identified by exome analysis. All patients described here presented with moderate to severe global developmental delay and variable disease progression. Seizures, truncal hypotonia and movement disorders were frequently observed. Notably, we also present the first eight cases in which the recurrent p.(Asp148Tyr) variant was not detected in either homozygous or compound heterozygous state.We cloned and expressed all novel and most previously published non-truncating variants in HEK293-cells. From the results of these functional studies, we propose a potential genotype-phenotype correlation, with a greater reduction in protein expression being associated with a more severe phenotype.Taken together, our findings broaden the known phenotypic and molecular spectrum and emphasize that NHLRC2-related disease should be considered in patients presenting with intellectual disability, movement disorders, neuroregression and epilepsy with or without pulmonary involvement.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy that derives from precursors of plasmacytoid dendritic cells and is characterized by disseminated, erythematous or bluish-livid plaques or nodi. Because of the disease's rarity the diagnosis and treatment still pose a significant challenge. We present a case of a patient with BPDCN and show clinical and diagnostic characteristics as well as potential treatment regimes.

Objectives: The aims are (a) assessment of the prevalence of psychosocial emergencies in the emergency department (ED), (b) determination of the proportion of cases not coded as diagnosis (unreported cases), and (c) characterization of identified patients.Methods: In a retrospective study, psychosocial emergencies in one week were identified from routine documentation of the central ED of the Charite - Universitatsmedizin Berlin, Charite Campus Mitte (CCM). After exclusion of planned admitted cases, 862 patients were included in the study. The identified psychosocial emergencies were descriptively analyzed with regard to their sociodemographic and clinical characteristics and compared with other emergencies.Results: The prevalence of psychosocial emergencies in the reported period was 11.9% (n = 103). A large proportion of psychosocial emergencies were not coded (35.9%) or not fully coded (20.4%) as an ICD diagnosis (unreported cases). There was a statistically relevant difference in gender distribution with a significantly higher proportion of males among psychosocial emergencies (70.9%) compared to other emergencies (50.7%; p < 0.0001). The two most common treatment causes among psychosocial emergencies were substance abuse (66.0%) and homelessness (20.4%).Conclusions: This study shows a relevant proportion of psychosocial emergencies among all treatments in ED routine data and a high proportion of cases not captured in the coded diagnoses. EDs thus represent an important point of contact for vulnerable patient groups but standardized screening and identification are still lacking.

Autoimmune encephalitides are seldom diseases. How rare they actually are, however, is not known. The low incidence combined with the problematic identification may dampen efforts of neurologists, to identify patients with unclear symptoms as suffering from autoimmune encephalitis. Here, we aim to obtain a better estimate, how many patients with autoimmune disorders should be expected among 100 inpatients in a conventional neurological department. From a total number of 2603 non-stroke patients attended in a 2-year period (2018-2019) 460 CSFs were obtained. From this collection 187 samples (40.7%, > 500 sections) could be analyzed with our immunocytochemical technique. Autoreactive antibodies were detected in 102 (55%) of these 187 CSF samples. Certainly, the presence of autoreactive antibodies does not necessarily indicate that the patient suffers from an autoimmune disease. Our data indicate that from roughly 2000 patients during 1 year about 125 patients with autoreactive CSF antibodies should be expected in a conventional neurological department. This represents the about 35-fold value of what is generally expected at present. Being aware of this high incidence may intensify the efforts of neurologist to identify patients with any type of autoimmune encephalitis. This will be beneficial for patients, because they often profit from immunomodulatory therapy. Interestingly, some CFSs from our patients react with the CA2 subdivision of the hippocampus. While long neglected, recent research places this area into an important position to influence hippocampal network physiology. Autoreactive antibodies in the CSF may disturb the function of CA2 neurons, thereby explaining some neuropsychiatric symptoms in patients with autoimmune encephalitides.

Background: Until now the long-term consequences of the medical treatment for bipolar disorder have barely been examined, especially the consequences with respect to cognitive impairment and dementia. Some studies show signs that some treatment options have a better effect on the brain than others. This review summarizes the current state of research. Objective: The effects of long-term consequences of lithium, valproic acid, carbamazepine and antipsychotic agents on the development of dementia or cognitive impairments in patients with bipolar disorder were investigated. Methods: A systematic literature search was carried out in the PubMed data base from May to July 2022. Results: The majority of studies showed that lithium has a neuroprotective effect and can lower the risk of developing dementia, whereas an increased risk was found in patients taking valproic acid. There are only very few studies that deal with antipsychotic medication and the long-term consequences concerning dementia. Conclusion: Lithium should be recommended for the long- term treatment of bipolar disorder. Valproic acid should not or carefully be used as it can affect the risk of developing dementia. With respect to antipsychotics there is no recommendation as more studies are needed to evaluate the long-term consequences.

Background and purpose: C-reactive protein serves as a marker of inflammation and is linked to depression in the general population. We aimed to assess whether elevated baseline levels of high-sensitivity C-reactive protein (hs-CRP) are associated with depressive symptoms over time in a prospective cohort of mild-to-moderate first-ever ischemic stroke patients.Methods: Data were obtained from the Prospective Cohort with Incident Stroke Berlin (NCT01363856). Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D) at three annual follow-up points. We assessed the association of elevated levels of hs-CRP with CES-D scores over time via linear mixed models. In a subgroup analysis, we explored an interaction effect with sex.Results: We included 585 ischemic stroke patients with baseline data on CRP levels. The mean age was 67 (13 SD), 39% (n = 226) were female, and the median National Institutes of Health Stroke Scale (NIHSS) was 3 (IQR 1-4). Twenty percent of survivors showed evidence for depressive symptoms one year after stroke with CES-D >= 16, 21% at year two, and 17% at year three. Higher log-transformed baseline hs-CRP levels were associated with higher CES-D Scores over time in the adjusted linear mixed model (beta = 1.28; (95% CI 0.22-2.34)). The subgroup analysis revealed an interaction effect of hs-CRP on depressive symptoms in women (beta = 2.33; (95% CI 0.71-3.95)).Conclusion: In our cohort with mild-to-moderate first-ever ischemic stroke patients, hs-CRP levels were associated with more depressive symptoms over time, with an interaction effect for the female sex.Study registration: https://clinicaltrials.gov; Unique identifier: NCT01363856.