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Background: Intracranial bleeding (ICB) is a serious complication during veno-venous extracorporeal membrane oxygenation (V-V ECMO), with potentially fatal consequences. Purpose: This study aimed to evaluate the incidence, time of detection of ICB among patients treated with V-V ECMO and potential risk factors for developing ICB during V-V ECMO. Methods: Five hundred fifty six patients were included in this retrospective single center analysis. Results: Median time on V-V ECMO was 9 (IQR 6-15) days. Intracranial bleeding during V-V ECMO was detected in 10.9% of all patients (61 patients with ICB). Only 17 patients with ICB presented obvious clinical symptoms. Intracranial bleeding was detected on cerebral imaging in median after 5 days (IQR 1-14) after starting V-V ECMO. Overall survival to hospital discharge was 63.7% (ICB: 29.5%). Risk factors of ICB before starting V-V ECMO in univariable analysis were platelets <100/nl (OR: 3.82), creatinine >1.5mg/dl (OR: 1.98), norepinephrine >2.5mg/h (OR: 2.5), ASAT >80U/L (OR: 1.86), blood-urea >100mg/dl (OR: 1.81) and LDH >550u/L (OR: 2.07). Factors associated with cannulation were rapid decrease in paCO2 >35mmHg (OR: 2.56) and rapid decrease in norepinephrine >1mg/h (OR: 2.53). Multivariable analysis revealed low platelets, high paCO2 before ECMO, and rapid drop in paCO2 after V-V ECMO initiation as significant risk factors for ICB. Conclusion: The results emphasize that ICB is a frequent complication during V-V ECMO. Many bleedings were incidental findings, therefore screening for ICB is advisable. The univariate risk factors reflect the underlying disease severity, coagulation disorders and peri-cannulation factors, and may help to identify patients at risk. [ABSTRACT FROM AUTHOR]

Background: Infantile nephropathic cystinosis (INC) is a rare lysosomal storage disorder, mostly and often firstly affecting the kidneys, together with impaired disharmonious growth and rickets, eventually resulting in progressive chronic kidney disease (CKD). With the introduction of cysteamine therapy, most pediatric patients reach adulthood with no need for kidney replacement therapy. Still, detailed changes in INC patients' clinical and morphological presentation over the past decades have not yet been thoroughly investigated. Methods: Two groups with a respective total of 64 children with INC and 302 children with CKD, both treated conservatively and aged 2 to 18 years, were prospectively observed in the time span from 1998 to 2022 with 1186 combined annual clinical and morphological examinations clustered into two measurement periods (1998 to 2015 and ≥ 2016). Results: In INC patients, thoracic proportion indices remained markedly increased, whereas body fat stores remained decreased over the past 25 years (+ 1 vs. below ± 0 z-score, respectively). Their CKD peers presented with overall improved growth, general harmonization of body proportions, and improved body fat stores, while INC patients only presented with an isolated significant increase in leg length over time (∆0.36 z-score). eGFR adjusted for age did not significantly change over the past 25 years in both groups. Alkaline phosphatase (ALP) showed a significant decrease in CKD patients over time, while remaining above normal levels in INC patients. Conclusions: Disproportionate thoracic shape and impaired body fat stores remain the most characteristic morphological traits in INC patients over the past 25 years, while causal mechanisms remain unclear. [ABSTRACT FROM AUTHOR]

Background: The treatment results of the Ponseti method for arthrogrypotic clubfoot have been described in only a few case series. Further evaluations are necessary. Methods: Children from two German paediatric orthopaedic hospitals with arthrogryposis-associated clubfoot treated with the Ponseti method between 2004 and 2011 and who were at least five years of age at their last follow-up were retrospectively evaluated. The endpoints were the clinical foot position, necessary surgeries during the follow-up period and radiological constellations. A comprehensive literature review was conducted after a systematic literature search. Results: Seventeen patients (47% with amyoplasia [AP] and 53% with distal arthrogryposis [DA]) met the inclusion criteria. Thirty-one feet were evaluated. The period between the treatment start and the last follow-up examination covered 8.9 ± 2.5 years. After the last cast removal within the initial Ponseti cast series, 74% of the clinical results were good to excellent. However, the clinical outcomes in the patients with AP were significantly worse. Overall, in 23 feet (74%), at least one major surgery at the age of 2.9 ± 2.2 years was necessary during the clinical course. Major surgeries were much more frequent on the feet of the patients with AP than with DA. Lateral X-rays showed normal age-appropriate radiological angles in 4% of the feet, hindfoot equinus in 19%, under-corrected hindfoot in 44%, under-corrected clubfoot in 26% and rocker bottom deformity in 7%. The radiological residual deformities in AP were much more severe than in DA (p = 0.042). Most of the studies reviewed (11 case series, 144 patients) reported high initial clinical correction rates, followed by high recurrence rates and the need for further surgeries. Conclusion: About a quarter of the arthrogrypotic patients benefited from the Ponseti therapy without further major surgery. However, the clinically observed high initial correction rate after Ponseti therapy of arthrogrypotic clubfoot was not accompanied by a correction of the bony foot position in the X-rays. The feet of the patients with DA had better outcomes than those of the patients with AP. Therefore, in outcome studies, a clear distinction between patients with AP and those with DA is necessary. [ABSTRACT FROM AUTHOR]

Objectives: The LYMQOL is the most frequently translated, validated, objective tool for assessing Health-Related Quality of Life (HRQoL) in individuals with upper limb lymphedema (ULL). There have been adaptations and validations in a number of different countries. While a German version of LYMQOL Leg for lower limb lymphedema is available, a validated translation of LYMQOL Arm to German is lacking. We aimed to perform a cross-cultural adaption and translation according to ISPOR principles. Methods: Patients suffering from ULL from Germany, Austria, and Switzerland (n = 52) were questioned twice using the translated LYMQOL Arm, SF-36, and an evaluation questionnaire. The assessment of the content validity and face validity proved this version of LYMQOL Arm to be acceptable for interviewing German-speaking patients with ULL in Germany. Results: Comparison of LYMQOL Arm and SF-36 demonstrated good construct validity. Test–retest reliability was moderate to good (intraclass correlation coefficients 0.66–0.73). Cronbach's alpha values varied between 0.79 and 0.89 in both interviews, indicating good internal consistency. Factor analysis revealed a cumulative variance of 59.5% for the four domains of the questionnaire. Conclusion: There was no significant association between lymphedema stage and LYMQOL Arm score. This trial tested the appropriateness of the German version of the LYMQOL Arm for measuring HRQoL in German-speaking individuals with ULL. [ABSTRACT FROM AUTHOR]

AbstractPurposeMethodResultConclusionThe purpose of this study was to assess the long-term stability of objective and subjective psychosocial improvements and fluency more than 10 years after participation in an intensive stuttering therapy camp.Ten former participants in intensive stuttering therapy (IST; mean age at time of intervention 14; 2 years) participated in this study. Outcomes of the IST at that time were assessed with the Stuttering Severity Instrument (SSI-3; Riley, 1994) and a questionnaire to measure the psychosocial impact of stuttering. A semi-structured video call and a general questionnaire for the long-term evaluation were used to gauge the participants’ perceptions of the IST. These follow-up data were compared to the therapy outcomes reported by Cook (2011, 2013).Therapy effects on the severity of stuttering and psychosocial impact were stable over the follow-up period of more than 10 years. Moreover, scores for psychosocial impact and severity of stuttering further decreased from the end of the IST to the long-term evaluation. The intensive time and the periodically offered follow-up treatments were described as particularly positive by the participants.Intensive stuttering therapy in childhood or adolescence can have a long-term positive effect on both internal and external stuttering symptoms. [ABSTRACT FROM AUTHOR]

Purpose: Whole-body computer tomographic examinations (WBCT) are essential in diagnosing the severely injured. The structured clinical evaluation in the emergency trauma room, according to ATLS® and guidelines, helps to indicate the correct radiological imaging to avoid overtriage and undertriage. This retrospective, single-center study aimed to evaluate the value of WBCT in patients with an inconspicuous primary survey and whether there is any evidence for this investigation in this group of patients. Methods: This retrospective, single-center study was conducted with patients admitted to a maximum-care hospital and supraregional trauma center in Germany and part of the TraumaNetwork DGU® in southwest Germany between January 2012 and November 2017. Hospital files were used for evaluation, and WBCT was carried out using a 32-row MSCT device from Siemens Healthineers, Volume Zoom, Erlangen, Germany. For evaluation, non-parametric procedures such as the chi-square test, U test, Fisher test, and Wilcoxon rank sum test were used to test for significance (p < 0.05). Results: From 3976 patients treated with WBCT, 120 patients (3.02%) showed an inconspicuous primary survey. This examination did not reveal any trauma sequelae in any of this group. Additionally, 198 patients (4.98%) showed minor clinical symptoms in the primary survey, but no morphological trauma sequence could be diagnosed in WBCT diagnostics. Three hundred forty-two patients were not admitted as inpatients after WBCT and discharged to further outpatient treatment because there were no objectifiable reasons for inpatient treatment. Four hundred fifteen patients did not receive WBCT for, e.g., isolated extremity trauma, child, pregnancy, or death. Conclusion: Not one of the clinically asymptomatic patients had an imageable injury after WBCT diagnostics in this study. WBCT should only be performed in severely injured patients after clinical assessment regardless of "trauma mechanism." According to guidelines and ATLS®, the clinical examination seems to be a safe and reliable method for reasonable and responsible decision-making regarding the realization of WBCT with all well-known risk factors. [ABSTRACT FROM AUTHOR]

Background: Tularaemia is a zoonotic disease caused by Francisella tularensis, a highly virulent bacterium that affects humans and small wild animals. It is transmitted through direct contact with infected animals or indirectly through contaminated soil, water or arthropod bites (e.g. ticks). Primary thoracic manifestations of tularaemia are infrequent and, therefore, a diagnostic challenge for clinicians. Methods: We report six tularaemia cases with exclusively thoracic involvement diagnosed in a clinic for pulmonary diseases in Bavaria between 10/2020 and 02/2022. Results: All patients lived or were active in rural areas, four reported a recent tick bite. All patients presented with thoracic lymphadenopathy and pulmonary tumours or consolidations; all underwent bronchoscopy with EBUS-TBNA of lymph nodes, three lung biopsies as well. Five patients showed inflammatory changes in the endobronchial mucosa. The main histological findings were necrotic epithelioid granulomas with remarkable granulocyte infiltration. All cases were identified by positive serology, five by PCR (here identification of F.t. ssp. Holarctica) from biopsy as well. As first-line therapy, oral ciprofloxacin was given (5/6); in 2/6 cases, a combination of quinolone–rifampicin was given. Conclusions: Pulmonary tularaemia may occur after tick bites and without extrathoracic manifestations. In patients who present with thoracic lymphadenopathy and pulmonary consolidations and who are exposed to increased outdoor activities, tularaemia should be included in the diagnostic pathway. Histologically, the presence of neutrophil–granulocyte infiltrations might help to distinguish tularaemia from other granulomatous infections, e.g. tuberculosis. The combination of quinolone–rifampicin rather than i.v. gentamicin reduced length of hospital stay in two patients. [ABSTRACT FROM AUTHOR]

Background: Mental health and health-related quality of life (HRQoL) in children and adolescents deteriorated during the COVID-19 pandemic. The aim of this population-based longitudinal study was to explore whether distinct mental health trajectories in youths can be identified over the course of the pandemic. Methods: Mental health problems (MHP), psychosomatic symptoms and HRQoL were assessed at five time points between May 2020 and October 2022 in 744 children and adolescents aged 7 to 20 years using established instruments. We used generalized mixture modeling to identify distinct mental health trajectories and fixed-effects regressions to analyse covariates of the identified profiles of change. Results: We found five distinct linear latent trajectory classes each for externalising MHP and psychosomatic symptoms and four trajectory classes for internalising MHP. For HRQoL, a single-class solution that indicates a common development process proved to be optimal. The largest groups remained almost stable at a low internalising and externalising symptom level (64 to 74%) and consistently showed moderate psychosomatic symptoms (79%), while 2 to 18% showed improvements across the pandemic. About 10% of the youths had consistently high internalising problems, while externalising problems deteriorated in 18% of youths. Class membership was significantly associated with initial HRQoL, parental and child burden, personal resources, family climate and social support. Conclusions: The mental health of most children and adolescents remained resilient throughout the pandemic. However, a sizeable number of youths had consistently poor or deteriorating mental health. Those children and adolescents need special attention in schools and mental health care. [ABSTRACT FROM AUTHOR]

Simple Summary: This study analyzes 61 rare tumors and lesions mimicking peripheral nerve tumors using data from the German Peripheral Nerve Tumor Registry. These cases exhibit significant heterogeneity with various morphological features and biological potentials, including malignant peripheral nerve tumors, perineuriomas, and hybrid nerve sheath tumors. This study underscores the challenges in preoperatively differentiating these rare entities from benign tumors using clinical and radiological methods alone. It highlights the importance of a multidisciplinary approach involving radiologists, neurologists, neuropathologists, and neurosurgeons for accurate diagnosis and effective treatment. The supplementary material offers valuable insights to help clinicians recognize these rare tumors early, improving patient outcomes. The most common peripheral nerve tumors are of a benign nature and include schwannoma or neurofibroma. In rare cases, other tumors or non-tumorous lesions can mimic peripheral nerve tumors clinically or radiologically. Based on data from the multicentric German Peripheral Nerve Tumor Registry (PNTR), which encompasses current information on 315 surgically treated patients from three high-volume centers, we present 61 cases of rare tumors and lesions that mimic tumors associated with peripheral nerves. This cohort displays considerable heterogeneity, featuring a broad spectrum of morphological features and biological potentials. Histopathological diagnoses include various intrinsic peripheral nerve tumors such as malignant peripheral nerve tumors (MPNSTs) (n = 13), perineurioma (n = 17), and hybrid nerve sheath tumors (HPNSTs, comprising schwannoma/perineurioma and schwannoma/neurofibroma) (n = 14), as well as atypical neurofibromatous neoplasm with unknown biological potential (ANNUBP) (n = 1). Additionally, the cohort encompasses extrinsic tumorous lesions like lymphoma (n = 3), lymphangioma (n = 2), hemangioma (n = 2), solitary fibrous tumor (n = 2), metastatic disease (n = 1), and single cases of other rare tumor entities (n = 6). An overview of the underlying pathology, imaging features, and clinical presentation is provided, with a brief description of each entity. A definitive preoperative differentiation between benign peripheral nerve tumors and rare intrinsic and extrinsic tumors is often not possible. Clinical examination and subtle imaging clues can at least indicate the possibility of a rare entity. The basic requirement is close cooperation between radiologists, neurologists, neuropathologists, and neurosurgeons at a specialized center to develop a multidisciplinary concept and offer the patient the best therapeutic approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: Taste and smell alterations (TSAs) are a distressing yet underdiagnosed side effect in cancer patients undergoing chemotherapy. However, long-term investigations using both questionnaires and chemosensory tests are scarce. We examined the prevalence of quantitative and qualitative TSAs, as well as their connection with clinical characteristics such as age, sex, anorexia, and neuropathy. We also compared patients receiving perpetual or temporary chemotherapy. All patients were examined up to five times within 12 to 24 months, commencing before the beginning of chemotherapy. We found TSAs in approximately 4 out of 5 patients during chemotherapy. The highest prevalence was documented among patients above 60 years of age as well as among those reporting anorexia or presenting signs of neuropathy. Post-therapy, taste and smell function recovered; however, scores did not reach baseline levels within 6 to 12 months. Future investigations will assess potential interventions to prevent or reduce TSAs. Previous data regarding chemotherapy-induced olfactory and gustatory dysfunction (CIOGD) are heterogeneous due to inconsistent study designs and small numbers of patients. To provide consistent, reliable data, we conducted a cohort study using standardized testing. Patients diagnosed with lymphoma, leukemia, or gastrointestinal malignancies were examined up to five times (T1 to T5), beginning prior to chemotherapy. We examined patients receiving temporary treatment up to 12 months post-therapy. Clinical assessment included extensive questionnaires, psychophysical tests of olfactory and gustatory function, and measurement of peripheral neuropathy. Statistical analysis included non-parametric tests to evaluate the longitudinal development of CIOGD. Our data (n = 108) showed a significant decline in olfactory and gustatory testing during chemotherapy (p-values < 0.001). CIOGD appeared stronger among patients above 60 years, while sex did not matter significantly. However, we identified distinct associations between CIOGD and reported anorexia as well as with higher neuropathy scores. Self-assessment appeared less sensitive to chemosensory dysfunction than psychophysical testing. Post-therapy, olfactory and gustatory function regenerated, though baseline levels were not attained within 6 to 12 months. In conclusion, our data highlight the wide prevalence and slow recovery of CIOGD. Understanding CIOGD as a potential neurotoxic effect may disclose new therapeutic prospects. [ABSTRACT FROM AUTHOR]

Background: Symptom validity tests (SVTs) and performance validity tests (PVTs) are important tools in sociomedical assessments, especially in the psychosomatic context where diagnoses mainly depend on clinical observation and self-report measures. This study examined the relationship between reaction times (RTs) and scores on the Structured Inventory of Malingered Symptomatology (SIMS). It was proposed that slower RTs and larger standard deviations of reaction times (RTSDs) would be observed in participants who scored above the SIMS cut-off (>16). Methods: Direct surface electromyography (EMG) was used to capture RTs during a computer-based RT test in 152 inpatients from a psychosomatic rehabilitation clinic in Germany. Correlation analyses and Mann-Whitney U were used to examine the relationship between RTs and SIMS scores and to assess the potential impact of covariates such as demographics, medical history, and vocational challenges on RTs. Therefore, dichotomized groups based on each potential covariate were compared. Results: Significantly longer RTs and larger RTSDs were found in participants who scored above the SIMS cut-off. Current treatment with psychopharmacological medication, diagnosis of depression, and age had no significant influence on the RT measures. However, work-related problems had a significant impact on RTSDs. Conclusion: There was a significant relationship between longer and more inconsistent RTs and indicators of exaggerated or feigned symptom report on the SIMS in psychosomatic rehabilitation inpatients. Findings from this study provide a basis for future research developing a new RT-based PVT. [ABSTRACT FROM AUTHOR]

Background: Child ADHD symptoms are highly prevalent in middle childhood, alongside impairment in social functioning. The parent–child relationship has been shown to play an important role; however, studies investigating specific facets of the parent–child relationship in ADHD symptomatology in middle childhood have been neglected. We assumed that higher ADHD symptoms were associated with both (1) lower maternal emotional availability (EA) and (2) lower child attachment security. Moreover, (3) we aimed to explore which specific EA dimensions were associated with ADHD symptoms. Methods: In a socio-pediatric clinic in Germany, 71 inpatient mother–child dyads (child age: M = 7.70, SD = 1.06; n = 54 boys) were assessed. Clinical data about child ADHD symptoms (Child Behavior Checklist 6–18 subscale "attention deficit/hyperactivity problems"), maternal EA (free play), and child attachment representation (Attachment Story Completion Task, GEV-B) were analyzed cross-sectionally. Results: Controlling for child oppositional behavior and sex, child ADHD symptoms were associated with overall maternal EA, and more specifically non-hostility, but not with child attachment representation. Conclusions: Our results imply that the role of parent–child interaction quality should be considered in the treatment of ADHD. Bidirectional effects cannot be ruled out. [ABSTRACT FROM AUTHOR]

Objectives To analyse genetic mechanisms triggering familial sarcoidosis, whole exome screening of a family of six persons with four cases of sarcoidosis and two healthy controls was performed integrating progressive and spontaneous remission cases and evaluating involved genetic alterations that could potentially determine the individual course of the disease. Methods Clinical diagnostic criteria in patients of the selected sarcoidosis family were according to American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and other Granulomatous Disorders guidelines. Exome screening of four patients and the two intrafamilial healthy relatives was performed by paired-end (2 × 100 bp) sequencing. We then selected the gene variants considered pathogenic on the basis of a series of prediction software applications and presence only in members of the family affected by sarcoidosis, after subtracting the common variations observed in healthy subjects. Results Four persons out of six family members were affected by sarcoidosis. Fifty genes with uncommon in silico pathogenic variants could be identified that differentiated affected and healthy family members. One patient with sarcoidosis showed spontaneous remission whereas the remaining three patients required immunosuppressive treatment. Subtraction analysis revealed 18 genes that distinguished the three progressive cases from the patient with spontaneous remission. Conclusion The genetic analysis of these cases with familial sarcoidosis identified several involved genes and functional pathways that could help in understanding the basic mechanisms that determine the development of the disease and that discriminate spontaneously regressive and progressive forms. [ABSTRACT FROM AUTHOR]

Background: To clinically evaluate how dry eye symptoms in preoperatively diagnosed dry eye patients change with the use of sodium hyaluronate- and dexpanthenol-containing eye drops (HYLO CARE (HC), URSAPHARM Arzneimittel GmbH, Saarbruecken, Germany) after cataract surgery. The aim of the study was not to compare different eye drops but to implement standard treatment in patients with dry eye undergoing cataract surgery. The impact of treatment was evaluated using Symptom Assessment Tools for Dry Eye. Methods: In this prospective, single-center, open-label clinical trial, 49 patients undergoing cataract surgery were included who showed signs and symptoms of dry eye disease assessed by the Symptom Assessment in Dry Eye (Visual Analogue Scale (VAS)) questionnaire, Ocular Surface Disease Index (OSDI), and fluorescein tear break-up Time (TBUT). Patients were instructed to apply HC three to four times a day for 5 weeks in the operated eye in addition to the standard postoperative topical anti-inflammatory regimen. The primary endpoint was the change in TBUT. Secondary endpoints were the assessment of the subjective symptoms (VAS), corrected distance visual acuity (CDVA), and slit-lamp examination including the corneal staining score, Schirmer test, and intraocular pressure. Results: At 5 weeks after operation, the mean TBUT increased from 6.42 ± 1.57 s (s) to 7.81 ± 1.83 s in the per-protocol (PP) population (p > 0.001) and from 6.33 ± 1.64 s to 7.71 ± 2.05 s in the intention-to-treat (ITT) population (p < 0.001). There was a statistically significant decrease in all scores (p < 0.05) from the VAS questionnaire except for the tearing score (p = 0.062) at 5 weeks after operation. The mean total corneal staining score also decreased statistically significantly from 8.85 ± 2.49 before operation to 5.61 ± 3.37 at 5 weeks after operation on a 15-point scale. Conclusions: Controlled standardized dry eye treatment (with HC) improved tear film stability, ocular surface defects, and subjective symptoms of dry eye disease in patients 5 weeks after undergoing cataract surgery. Both the patient and physician assessments indicated high efficacy, tolerability, and a reliable safety profile, as indicated by the low number of at least possibly related adverse events (AE), suggesting its beneficial role in the postoperative management of the ocular surface (OS) in patients with dry eye symptoms prior to and after cataract surgery. [ABSTRACT FROM AUTHOR]

Abstract: The legal neuropsychological assessment of individuals following infection with the Coronavirus disease 2019 (COVID-19) who exhibit potential symptoms of the Post-COVID-Syndrome (PCS) not only requires adherence to local regulations but also consideration of general professional guidelines. The assessment of PCS proves challenging both for the individual and the evaluator in the presence of ambiguous functional deficits or causal relationships. This article offers an overview of pathogenetic findings relevant to legal assessment and reflects on current German regulations and frameworks. In Germany, the legal neuropsychological assessment of PCS should align with guidelines of the Gesellschaft für Neuropsychologie (GNP) and integrate published neurological criteria. As PCS research rapidly advances, an interdisciplinary professional exchange is vital for further refining the legal neuropsychological assessment of PCS. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to describe clinical, virological and radiological characteristics as well as treatment strategies and outcomes of immunocompromised patients with persistent SARS-CoV-2 replication. Methods: We performed a retrospective cohort study of immunocompromised patients at the University Medical Center Freiburg between 01/2022 and 05/2023. Patients with substantial immunosuppression and persistent SARS-CoV-2 detection (Ct-value < 30 after 14 days) were included. Results: 36 patients in our cohort reported mainly fever, dyspnoea or continuous cough. Viral load was significantly higher in concurrent samples taken from the lower respiratory tract (Ct-value = 26) than from the upper respiratory tract (Ct-value = 34). Time of detectable viral RNA after start of antiviral treatment was shorter in patients receiving two antivirals (median 15 days vs. 31 days with one antiviral agent). Short-course antiviral therapy (≤ 5 days) was less efficient in reduction of symptoms and viral load than prolonged therapy > 10 days. In 30% (8/27) of patients with repeated CT scans, we found the emergence of chronic pulmonary changes, which were more frequently in patients with B cell depletion (37%, 7/19) compared to patients with organ transplantation (12%, 2/17). Conclusion: Ongoing SARS-CoV-2 replication in the lower respiratory tract is a relevant differential diagnosis in patients with severe immunosuppression and continuous cough, fever or dyspnoea even if nasopharyngeal swabs test negative for SARS-CoV-2. Especially in B cell-depleted patients, this may lead to inflammatory or fibrotic-like pulmonary changes, which are partially reversible after inhibition of viral replication. Antiviral therapy seems to be most effective in combination and over a prolonged period of time of > 10 days. Trial registration number: DRKS 00027299. [ABSTRACT FROM AUTHOR]

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Purpose: To describe the clinical characteristics of refugees with HIV from Ukraine that seek continuation of medical care in Germany. Methods: Fourty‐six refugees with HIV that had left Ukraine between 24 February and 30 December 2022 were examined. Information on patients' history was obtained using a standardized questionnaire for clinical care. Interviews were conducted in Russian during their first clinical presentation. Results: Fourty‐six persons (41 females and 5 males) were included and their mean age was 39.6 (±8.4) years. The mean time since HIV diagnosis was 8.0 (median, IQR 7.15) years and 70.3% of participants currently received tenfofovir‐DF, lamividine and dolutegravir. Most refugees had an undetectable HIV viral load and their current mean CD4 T cell count was 702 (SD ± 289) per μL. Serology revealed previous hepatitis B infection in 50.4% without evidence for replication, with undetectable anti‐hepatitis B surface antigen in the remaining refugees. Antibodies against hepatitis C were present in 23 refugees (50%), but only 10 patients had been diagnosed with hepatitis C previously. Five refugees had undergone successful antiviral treatment for hepatitis C. Detectable HCV‐RNA was evident in nine patients (19.6%). Sixteen (38.6%) refugees had a positive tuberculosis (TB) interferon gamma release assay, and four were on TB treatment for previously diagnosed infection. One had been diagnosed with multidrug‐resistant (MDR) TB, two with pre‐extensively drug‐resistant (pre‐XDR) TB and two with XDR TB and were treated with combinations of second‐line and novel agents according to WHO guidelines. Conclusions: Based on this preliminary analysis of a not fully representative cohort, refugees with HIV from Ukraine were young, mostly healthy females highly adherent to antiretroviral therapy. The rate of transmittable co‐infections urges early diagnostic evaluation and treatment. [ABSTRACT FROM AUTHOR]

Purpose: This study examined the characteristics, incidence and prognostic factors of the first AIDS-defining condition developed after more than one year of continuous antiretroviral therapy (ART) among people living with HIV (PLHIV). Methods: We used data from two multicentre observational cohorts of PLHIV in Germany between 1999 and 2018. Our outcome was the first AIDS-defining event that occurred during follow-up after more than one year of continuous ART. Descriptive analyses at ART initiation, at the time of the AIDS event and of the most frequently observed types of AIDS-defining illnesses were performed. We calculated the incidence rate (IR) per 1000 person-years (PY) and used a bootstrap stepwise selection procedure to identify predictors of the outcome. Results: A total of 12,466 PLHIV were included in the analyses. 378 developed the outcome, constituting an overall IR of 5.6 (95% CI 5.1–6.2) AIDS events per 1000 PY. The majority of PLHIV was virally suppressed at the time of the event. Oesophageal candidiasis and wasting syndrome were the most frequently diagnosed AIDS-defining illnesses. We found a low CD4 count at ART initiation, a previous AIDS-defining condition and transmission through intravenous drug use to be meaningful prognostic factors of the outcome. Conclusion: The overall rate of AIDS-defining events among PLHIV under long-term ART was low, highlighting the importance of continuous treatment. PLHIV who started ART with indicators of impaired immune functioning were more susceptible to disease progression, suggesting that the public health response should continue to focus on early and sustained treatment for all PLHIV. [ABSTRACT FROM AUTHOR]

The Omicron variants BA.1, BA.2, and BA.5 caused several waves of SARS-CoV-2 in Germany in 2022. In this comparative study, public health data on SARS-CoV-2 infections from Mecklenburg-Western Pomerania, Germany, between January and October 2022 were examined retrospectively using Pearson's chi-squared tests and Fisher's exact tests for testing for statistical significance. Compared to BA.5 infections, BA.1 and BA.2 infections affected younger individuals aged up to 19 years significantly more often, whereas BA.5 infections occurred significantly more frequently in patients between 40 and 59 years of age when compared to BA.1 and BA.2. Infections with all three variants predominantly caused flu-like symptoms; nevertheless, there were significant differences between the reported symptoms of BA.1, BA.2, and BA.5 infections. Especially, the symptoms of 'fever', 'severe feeling of sickness', 'loss of taste', and 'loss of smell' were significantly more often present in patients with BA.5 infections compared to BA.1 and BA.2 cases. Additionally, BA.2 and BA.5 cases reported significantly more often the symptoms of 'runny nose' and 'cough' than BA.1-infected cases. Our findings indicate remarkable differences in the clinical presentations among the sub-lineages, especially in BA.5 infections. Furthermore, the study demonstrates a powerful tool to link epidemiological data with genetic data in order to investigate their potential impact on public health. [ABSTRACT FROM AUTHOR]

Background and purpose: Spinal cerebrospinal fluid (CSF) leaks may cause a myriad of symptoms, most common being orthostatic headache. In addition, ventral spinal CSF leaks are a possible etiology of superficial siderosis (SS), a rare condition characterized by hemosiderin deposits in the central nervous system (CNS). The classical presentation of SS involves ataxia, bilateral hearing loss, and myelopathy. Unfortunately, treatment options are scarce. This study was undertaken to evaluate whether microsurgical closure of CSF leaks can prevent further clinical deterioration or improve symptoms of SS. Methods: This cohort study was conducted using data from a prospectively maintained database in two large spontaneous intracranial hypotension (SIH) referral centers in Germany and Switzerland of patients who meet the modified International Classification of Headache Disorders, 3rd edition criteria for SIH. Patients with spinal CSF leaks were screened for the presence of idiopathic infratentorial symmetric SS of the CNS. Results: Twelve patients were included. The median latency between the onset of orthostatic headaches and symptoms attributed to SS was 9.5 years. After surgical closure of the underlying spinal CSF leak, symptoms attributed to SS improved in seven patients and remained stable in three. Patients who presented within 1 year after the onset of SS symptoms improved, but those who presented in 8–12 years did not improve. We could show a significant association between patients with spinal longitudinal extrathecal collections and SS. Conclusions: Long‐standing untreated ventral spinal CSF leaks can lead to SS of the CNS, and microsurgical sealing of spinal CSF leaks might stop progression and improve symptoms in patients with SS in a time‐dependent manner. [ABSTRACT FROM AUTHOR]

Background and Objective Occupations involving repetitive movements of the wrists, activities that require a lot of force, and hand-arm swinging are particularly likely to contribute to the development of hand and wrist complaints. The daily setup and dismantling of dialysis machines as part of the dialysis treatment process can strain the wrists and fingers of nurses. However, evidence regarding the relationship between the work activities of dialysis nurses and the incidence of hand and wrist complaints is limited. This study aimed to investigate the prevalence and severity of hand and wrist complaints among dialysis nurses in Germany and to relate these to their work activities. Methods An online survey was created and sent to 836 dialysis centres in Germany. The Nordic Musculoskeletal Questionnaire was used in an online survey to assess the prevalence of musculoskeletal complaints in the hands and wrists. The Boston Carpal Tunnel Questionnaire (BCTQ) was used to assess symptom severity. Dialysis nurses rated the effort required to set up dialysis machines using the BORG-CR10 scale. The analysis was descriptive. Results A total of 122 dialysis nurses (18 male, 104 female; mean age 45 ± 12 years) participated in the survey, and 59% of them reported developing hands or wrist complaints in the last 12 months. According to BCTQ, the average severity of these complaints is 2.0 ± 0.8 (N = 72). The severity of symptoms increased significantly with the number of setups performed by a dialysis nurse per day (r s = 0.35, P  = 0.003, N = 72). The nurses rated the effort required to set up the dialysis machines as 2.8 ± 1.8 on the BORG-CR10 scale (N = 101). Discussion The results of the online survey showed that dialysis nurses were more likely than the general population to experience hand and wrist complaints. The repetitive activities of the hands and wrists while setting up a dialysis machine are thought to be the cause. Conclusions Preventive measures are needed to reduce hand and wrist strain in dialysis nurses. [ABSTRACT FROM AUTHOR]

Introduction: The German Registry of central serous chorioretinopathy (CSC) collects data on CSC patients in a nationwide multicenter approach to analyze epidemiology, risk factors, clinical presentations, as well as diagnosis and treatment patterns. Methods: In this multicenter cohort study, patients with CSC were enrolled in nine tertiary referral centers in Germany between January 2022 and June 2023. After consenting to the study, demographic data, risk factors, reported symptoms, best-corrected visual acuity (BCVA), funduscopic findings, disease severity, and diagnostic and treatment decisions were recorded and analyzed. Results: A total of 539 eyes of 411 CSC patients were enrolled in this study including 308 males (75%) and 103 females (25%). Patients were predominantly of Caucasian origin and had a mean age of 55.5 years (IQR 41.0–70.0). 28% of eyes were classified as acute (<4 months duration) CSC, 28% as chronic (>4 months duration) CSC, 21% as inactive CSC, 11% as chronic atrophic CSC, and 12% as CSC with secondary CNV. 128 patients (31%) demonstrated bilateral CSC. The most common risk factors reported were psychological stress (52%), smoking (38%), arterial hypertension (38%), and a history of or current use of steroids (30%). Most frequently encountered symptoms included decreased visual acuity (76%), metamorphopsia (49%), relative scotoma (47%), blurred vision (19%), and dyschromatopsia (9%). The mean logMAR BCVA on initial examination was 0.2 (≈20/30, IQR 0.2–0.4) but showed significant variation with a tendency of lower BCVA in chronic cases. At the baseline visit, 74% of the overall cohort received no treatment, while 19% underwent local treatment and only 2% underwent systemic treatment. Of the local therapies, anti-VEGF injections were the most frequently performed procedure (33%, mainly for secondary CNV), followed by micropulse laser (28%), focal nonpulsed laser (23%), verteporfin photodynamic therapy (14%), and nonsteroidal anti-inflammatory eye drops (2%). Among intravitreal anti-VEGF agents, aflibercept was used most frequently, followed by bevacizumab and ranibizumab. Conclusion: This registry represents one of the largest cohorts of European patients with CSC to date. Patient age and the proportion of women were higher than expected and bilateral active disease was lower than anticipated, highlighting that neither age nor gender should be overemphasized when diagnosing CSC. Therapeutic interventions are heterogeneous and include verteporfin photodynamic therapy, micropulse laser, and anti-VEGF injections in case of secondary CNV. [ABSTRACT FROM AUTHOR]

This article discusses a rare case of influenza and rapid progressive neurotuberculosis coinfection in a 22-year-old Indian woman living in Germany. The patient initially presented with high fever, joint pain, and headache, and was diagnosed with Influenza B. However, she was readmitted a few days later with worsening symptoms, including seizures and neurological deficits. Further testing revealed a Mycobacterium tuberculosis infection in the brain and spine. The article emphasizes the importance of interdisciplinary diagnostics, especially in migrants from low- and middle-income countries, and highlights the increasing prevalence of complex infections like tuberculosis in low-incidence countries. [Extracted from the article]

Somatic symptoms are common in a wide range of medical conditions. In severe cases, they are associated with high individual and economic burden. To explore social inequalities in somatic symptom severity (SSS) and to identify social groups with highest SSS, we applied an intersectional research approach. Analyses are based on cross-sectional data of the adult population living in Germany (N = 2413). SSS was assessed with the Somatic Symptom Scale-8. A multiple linear regression model with three-way interaction of gender, income and history of migration and post-hoc pairwise comparison of estimated marginal means was conducted. Analyses revealed intersectional inequalities in SSS along the axis of gender, income, and history of migration. Highest SSS was found in males with low income whose parent(s) immigrated, females with low income who immigrated themselves, and females with low income and no history of migration. Intersectional approaches contribute to a more comprehensive understanding of health disparities. To reduce disparities in SSS, proportionate universal interventions combining universal screening and targeted treatment seem promising. [ABSTRACT FROM AUTHOR]

Simple Summary: This longitudinal cohort study investigates the role of soluble Tumor Necrosis Factor Receptor 1 (sTNF-R1) in non-small-cell lung cancer (NSCLC) patients. Serum sTNF-R1 levels were measured in 134 NSCLC patients before, during, and after treatment at the Medical Faculty of Martin Luther University Halle-Wittenberg between 2017 and 2019. This study reveals that baseline sTNF-R1 levels were higher in NSCLC patients compared to the general population, and they exhibited a linear increase over time. Importantly, individual changes in sTNF-R1 levels during and after treatment were found to be strongly associated with the risk of mortality, highlighting the potential of the sTNF-R1 trajectory as a valuable prognostic marker in NSCLC. Background: Tumor necrosis factor (TNF) is a multipotent cytokine involved in inflammation and anti-tumor activity. TNF- α exerts its function upon binding to TNF-receptor 1 (TNF-R1) and TNF-receptor 2 (TNF-R2). This study investigates the relationship of soluble (s) TNF-R1 levels in non-small-cell lung cancer (NSCLC) patients with treatment and overall survival. Methods: In total, 134 NSCLC patients treated at the Medical Faculty of Martin Luther University Halle-Wittenberg between 2017 and 2019 were included in this study. Serum levels of sTNF-R1 were measured via ELISA at baseline and during and after treatment. A linear mixed-effects model was used to assess sTNF-R1 changes over time. Linear regression was applied to investigate the association between clinical characteristics and changes in sTNF-R1. Cox regression models were used to estimate associations with overall mortality. Results: The estimated average sTNFR-1 at baseline was 2091.71 pg/mL, with a change of 6.19 pg/mL per day. Cox models revealed that the individual change in sTNF-R1 was more strongly associated with mortality than its baseline value, especially after adjusting for covariates. Conclusions: This study provides evidence that the individual change in sTNF-R1 levels during and after treatment were associated with the risk of mortality, suggesting the use of the sTNF-R1 trajectory as a prognostic marker. [ABSTRACT FROM AUTHOR]

Purpose: The primary aim was to compare the prevalence of acute and delayed intracranial haemorrhage (ICH) following mild traumatic brain injury (mTBI) in patients on antithrombotic medication referred to a clinic for oral and plastic maxillofacial surgery. The secondary aim was to evaluate the need for short-term hospitalisation based on initial radiological and clinical findings. Methods: This was an observational retrospective single-centre study of all patients on antithrombotic medication who were admitted to our department of oral and plastic maxillofacial surgery with mTBI over a 5 year period. Demographic and anamnesis data, injury characteristics, antithrombotic medication, radiological findings, treatment, and outcome were analysed. Patients were divided into the following four groups based on their antithrombotic medication: (1) single antiplatelet users, (2) vitamin K antagonist users, (3) direct oral anticoagulant users, and (4) double antithrombotic users. All patients underwent an emergency cranial CT (CT0) at admission. Based on clinical and radiological evaluation, different treatment protocols were applied. Patients with positive CT0 findings and patients with secondary neurological deterioration received a control CT (CT1) before discharge. Acute and delayed ICH and patient's outcome during hospitalisation were evaluated using descriptive statistical analysis. Results: A total of 696 patients (mean age, 71.6 years) on antithrombotic medication who presented at our department with mTBI were included in the analysis. Most injuries were caused by a ground-level fall (76.9%). Thirty-six patients (5.1%) developed an acute traumatic ICH, and 47 intracerebral lesions were detected by radiology—most of these in patients taking acetylsalicylic acid. No association was detected between ICH and antithrombotic medication (p = 0.4353). In total, 258 (37.1%) patients were admitted for 48 h in-hospital observation. The prevalence of delayed ICH was 0.1%, and the mortality rate was 0.1%. Multivariable analysis identified a Glasgow Coma Scale (GCS) of < 15, loss of consciousness, amnesia, headache, dizziness, and nausea as clinical characteristics significantly associated with an increased risk of acute ICH, whereas age, sex, and trauma mechanism were not associated with ICH prevalence. Of the 39 patients who underwent a control CT1, most had a decreasing or at least constant intracranial lesion; in three patients, intracranial bleeding increased but was not clinically relevant. Conclusion: According to our experience, antithrombotic therapy does not increase the rate of ICH after mTBI. A GCS of < 15, loss of consciousness, amnesia, headache, dizziness, and nausea are indicators of higher ICH risk. A second CT scan is more effective in patients with secondary neurological deterioration. Initial CT findings were not clinically relevant and should not indicate in-hospital observation. [ABSTRACT FROM AUTHOR]

Background: Chronic spontaneous urticaria (CSU) is unpredictable and can severely impair patients' quality of life. Patients with CSU need a convenient, user‐friendly platform to complete patient‐reported outcome measures (PROMs) on their mobile devices. CRUSE®, the Chronic Urticaria Self Evaluation app, aims to address this unmet need. Methods: CRUSE® was developed by an international steering committee of urticaria specialists. Priorities for the app based on recent findings in CSU were defined to allow patients to track and record their symptoms and medication use over time and send photographs. The CRUSE® app collects patient data such as age, sex, disease onset, triggers, medication, and CSU characteristics that can be sent securely to physicians, providing real‐time insights. Additionally, CRUSE® contains PROMs to assess disease activity and control, which are individualised to patient profiles and clinical manifestations. Results: CRUSE® was launched in Germany in March 2022 and is now available for free in 17 countries. It is adapted to the local language and displays a country‐specific list of available urticaria medications. English and Ukrainian versions are available worldwide. From July 2022 to June 2023, 25,710 observations were documented by 2540 users; 72.7% were females, with a mean age of 39.6 years. At baseline, 93.7% and 51.3% of users had wheals and angioedema, respectively. Second‐generation antihistamines were used in 74.0% of days. Conclusions: The initial data from CRUSE® show the wide use and utility of effectively tracking patients' disease activity and control, paving the way for personalised CSU management. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate long-term outcomes in patients who underwent carotid artery stenting (CAS) for symptomatic or asymptomatic high-grade stenosis. Methods: A total of 1158 patients (asymptomatic, n = 636; symptomatic, n = 522) underwent CAS at our center between 2009 and 2020. A total of 560 patients or contacts (asymptomatic, n = 316; symptomatic, n = 244) were interviewed by telephone to evaluate long-term outcomes with a mean follow-up of 5 years. Mortality from all causes, myocardial infarction, and stroke, as well as comorbidities influencing their occurrence, including overall survival and stroke-free survival, were examined. Results: The overall survival rate for all-cause mortality was 91.6% at 1 year, 77.1% at 5 years, and 55.7% at 10 years. A total of 39 (6.9%) patients had an ischemic stroke during long-term follow-up. The stroke-free survival rates at 1 year, 5 years, and 10 years were 97.9%, 92.7%, and 86.6%, respectively. Stroke-free survival and overall survival did not differ significantly between the symptomatic and asymptomatic groups (overall survival, p = 0.304; stroke-free survival, p = 0.336). Regular physical activity reduced the risk of stroke and death and was associated with better long-term clinical outcomes. Age at treatment and diabetes mellitus were statistically significantly associated with death during follow-up. Conclusion: Long-term follow-up data confirmed the effectiveness and durability of CAS as a therapy option for both symptomatic and asymptomatic patients. In patient selection for CAS, special consideration should be paid to patient age, ability to engage in physical activity, and diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: The German S2k guideline is the first to include a checklist that captures atopic dermatitis (AD) signs and symptoms as well as the lack of treatment response to identify patients eligible for systemic therapy. Objectives: Identifying candidates for a start/switch of systemic therapy in adult AD patients in Germany by applying the S2k guideline's checklist. Methods: In this German multicentre, cross‐sectional, non‐interventional study (German Clinical Trials Register number: DRKS00023296), adult patients with mild to severe AD were enrolled at dermatological outpatient clinics and offices between April and October 2021. Demographics, clinical characteristics and quality of life were collected using questionnaires during one single visit. Eligibility for a start/switch of systemic AD therapy was evaluated according to the criteria of the German S2k guideline's checklist. Results: Atopic dermatitis patients (575) were included in the analysis. One hundred and sixty‐four patients (28.5%) received systemic (SYS) AD therapy and 411 patients (71.5%) did not (TOP). Of the TOP therapy patients, 38.7% were eligible to start systemic AD therapy, and about half of those (49.1%), were scheduled to start systemic AD therapy. The most frequent reason deciding against a systemic therapy was the patient's wish. Although 29.3% of SYS patients were eligible for a switch according to the criteria of the German S2k guideline's checklist, the majority (81.3%) did not switch AD therapy. Conclusions: This is the first study on the implementation of the German S2k guideline's checklist in everyday care of AD patients in Germany. More than one‐third of the TOP patients were identified as eligible for systemic treatment. By applying the guideline's checklist criteria, another one‐third of SYS patients may have benefited from a change of current systemic therapy. The use of the German S2k guideline's checklist in routine care represents an important tool to ensure effective patient care and identify inadequately treated patients. [ABSTRACT FROM AUTHOR]

The aims of this study were to analyze proton pump inhibitor (PPI) users in Germany, defining and classifying them in terms of treatment appropriateness, and to analyze the PPI prescription practices of healthcare providers. The updated DGVS (Deutsche Gesellschaft für Gastroenterologie, Verdauungs-und Stoffwechselkrankheiten) gastroesophageal reflux disease (GERD) treatment guideline (published March 2023) for mild heartburn symptoms recommends carrying out a probatory treatment of mild symptoms via other medication such as antacids, alginates, and H2 blockers before escalating to PPI treatments, if the patient profile allows. This retrospective cross-sectional study was based on data from the IQVIA™ Disease Analyzer database (DA) and included adult patients (18 years or older) in 1006 general and 39 gastroenterological practices in Germany who received at least 1 PPI prescription or alginate between September 2019 and September 2021 (hereinafter referred to as the index period). Analyses included indications associated with PPI prescription, co-diagnoses, co-therapies of PPI patients, duration of PPI therapy, dosages of PPI prescriptions, and proportions of practices prescribing PPIs and alginates. A total of 472 146 patients taking PPIs and 9101 patients taking alginates were available for analysis. Very few patients (4.5%) of the total cohort were treated in complete adherence to treatment guidelines. Conditions such as gastritis and duodenitis (47.2%) and reflux diseases (38.4%) were more frequently associated with PPI prescriptions. The average PPI treatment period lasted 141 days, and 36.6% of patients were treated for >6 months. High doses were prescribed relatively often (ie, 42.8% of esomeprazole prescriptions were 40 mg, 59.1% of lansoprazole prescriptions 30 mg, 28.6% of omeprazole prescriptions 40 mg). With each practice prescribing PPIs to at least 10% of their patients; 72% of general practitioners (GPs) and 8% of GENTS (Gastroenterologists) prescribed alginates. This study highlights that discrepancies exist between clinical guidelines and real-life prescribing practices of PPIs in Germany. Particular attention should be given to the incidence of patients being prescribed high-dose or long-duration PPI with mild indications. These findings are particularly apt considering the publication (March 2023) of new guidelines on the "management of gastroesophageal reflux disease and eosinophilic esophagitis," by the DGVS. [ABSTRACT FROM AUTHOR]

Copyright of Ergoscience is the property of Schulz-Kirchner Verlag Gmbh and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Signs and symptoms attributed to adverse reactions to foodstuffs (ARFS) need tools for research and evaluation in clinical practice. The objectives of this study were (a) to evaluate the most frequent self-reported signs and symptoms attributed to ARFS in Spanish adults, (b) to determine the prevalence of food-specific IgG4 antibody reactions (AbRs), and (c) to investigate the association between self-reported ARFS symptomatology and food-specific IgG4 AbRs. Food-specific IgG4 AbRs against 57 common food and beverages (AESKUCARE-T2FA® in vitro point-of-care test kit, Aesku.Diagnostics GmbH, Germany) were determined in capillary blood samples of 205 volunteers living in the Region of Madrid (Spain). The most frequent self-reported signs and symptoms were related to skin (43%), digestive (41%), and nervous system (NS, 33%) problems. The prevalence of food-specific IgG4 AbRs was cow's milk (73%), sheep's milk (70%), casein (66%), and goat's milk (56.10%). Positive IgG4 AbRs against tomato had a profile consisting of 3/4 of skin problems, more than half of digestive, and 2/5 of NS self-reported signs and symptoms. In conclusion, at least 1/3 of the studied sample reported skin, digestive, and NS signs and symptoms. The most frequent food-specific IgG4 AbRs were related to dairy. Skin problems were more frequent in positive tomato IgG4 AbRs. [ABSTRACT FROM AUTHOR]

Background: To assess quality of life and unmet needs after stroke, patient-reported outcome measures (PROMs) have gained increasing attention. However, patients' perspectives on assessing PROMs remain unclear, potentially hindering implementation into clinical practice. Therefore, this study explored patients' preferences on assessing PROMs after ischemic stroke. Methods: A paper-based questionnaire was sent to stroke survivors treated at the Department of Neurology, University of Leipzig, Germany. Health-related quality of life (HRQoL, EQ-5D-5L) and preferences regarding different aspects of data collection to assess PROMs were investigated and linked to socio-demographic and medical characteristics. Results: 158 persons were contacted and 80 replies were subsequently analyzed. Mean age was 70.16 years and mean HRQoL was 68.79 (visual analogue scale with a theoretical maximum of 100). Participants showed positive attitudes towards PROMs as they saw potential to improve care of other patients (n = 66/79; 83.54%) or to improve their own situation (n = 53/74; 71.62%). Participants preferred an annual interview after stroke (n = 39/80; 48.75%) and would preferably spend 15–30 min (n = 41/79; 51.90%) to answer a written survey (n = 69/80; 86.25%). The initially treating clinic was preferred as initiator of such surveys (n = 43/79; 54.43%). Stratification revealed that participants with more than 1 h of daily digital media usage preferred email as way of communication. Conclusions: For the first time, this study showed individual preferences on assessing PROMs after ischemic stroke, focusing on the way, time interval, duration, and initiation site of surveys. These insights might help to successfully implement PROMs after stroke and subsequently detect unmet needs and deficits in stroke care. [ABSTRACT FROM AUTHOR]

Background: Anaplasma phagocytophilum is a Gram-negative obligate intracellular bacterium that replicates in neutrophil granulocytes. It is transmitted by ticks of the Ixodes ricinus complex and causes febrile illness called granulocytic anaplasmosis primarily in humans, horses, dogs, sheep, cattle and goats. In comparison, clinically apparent disease has been described rarely in cats especially compared to dogs and horses. It is currently unknown whether cats are less susceptible to A. phagocytophilum or whether granulocytic anaplasmosis might be underdiagnosed in cats. Methods: To address this question, we examined clinical signs and laboratory findings in seven A. phagocytophilum infected cats from Germany and Switzerland. We then genetically characterized feline A. phagocytophilum strains and compared them to those from other hosts showing clinically apparent disease. For this purpose, ankA-based, groEL-based and multilocus sequence typing (MLST) were applied. Furthermore, the concordance between these typing methods was assessed. Results: Fever, lethargy and anorexia were the most common clinical signs in cats suffering from granulocytic anaplasmosis. The most frequent laboratory finding was thrombocytopenia. All three typing methods consistently indicated that the A. phagocytophilum strains found infecting cats are the same as those that cause disease in humans, dogs and horses. In general, the three typing methods applied exhibited high concordance. Conclusions: The genetic characterization of the feline A. phagocytophilum strains indicates that strain divergence is not the explanation for the fact that granulocytic anaplasmosis is much less frequently diagnosed in cats than in dogs and horses. Otherwise, it may be possible that cats are less susceptible to the same strains than dogs and horse are. However, due to the unspecific clinical signs, it should be considered that granulocytic anaplasmosis may be under-diagnosed in cats. [ABSTRACT FROM AUTHOR]

SEIR (Susceptible–Exposed–Infected–Recovered) approach is a classic modeling method that is frequently used to study infectious diseases. However, in the vast majority of such models transitions from one population group to another are described using the mass-action law. That causes inability to reproduce observable dynamics of an infection such as the incubation period or progression of the disease's symptoms. In this paper, we propose a new approach to simulate the epidemic dynamics based on a system of differential equations with time delays and instant transitions to approximate durations of transition processes more correctly and make model parameters more clear. The suggested approach can be applied not only to Covid-19 but also to the study of other infectious diseases. We utilized it in the development of the delay-based model of the COVID-19 pandemic in Germany and France. The model takes into account testing of different population groups, symptoms progression from mild to critical, vaccination, duration of protective immunity and new virus strains. The stringency index was used as a generalized characteristic of the non-pharmaceutical government interventions in corresponding countries to contain the virus spread. The parameter identifiability analysis demonstrated that the presented modeling approach enables to significantly reduce the number of parameters and make them more identifiable. Both models are publicly available. [ABSTRACT FROM AUTHOR]

Background: Specialist palliative home care (SPHC) aims to maintain and improve patients' quality of life in the community setting. Symptom burden may differ between oncological and non-oncological patients. However, little is known about diagnosis-related differences of SPHC patients. This study aims to describe the prevalence of physical symptom burden and psychosocial problems of adult patients in SPHC, and to evaluate diagnosis-related symptom clusters. Methods: Secondary analysis of data from a prospective, cross-sectional, multi-centre study on complexity of patients, registered at the German Register for Clinical Studies (DRKS trial registration number: DRKS00020517, 12/10/2020). Descriptive statistics on physical symptom burden and psychosocial problems at the beginning of care episodes. Exploratory and confirmatory factor analyses to identify symptom and problem clusters. Results: Seven hundred seventy-eight episodes from nine SPHC teams were included, average age was 75 years, mean duration of episode 18.6 days (SD 19.4). 212/778 (27.2%) had a non-oncological diagnosis. Main burden in non-oncological episodes was due to poor mobility (194/211; 91.9%) with significant diagnosis-related differences (χ² = 8.145, df = 1, p =.004; oncological: 472/562; 84.0%), and due to weakness (522/565; 92.4%) in oncological episodes. Two symptom clusters (psychosocial and physical) for non-oncological and three clusters (psychosocial, physical and communicational/practical) for oncological groups were identified. More patients in the non-oncological group compared to the oncological group showed at least one symptom cluster (83/212; 39.2% vs. 172/566; 30.4%). Conclusion: Patients with non-oncological diseases had shorter episode durations and were more affected by symptom clusters, whereas patients with oncological diseases showed an additional communicational/practical cluster. Our findings indicate the high relevance of care planning as an important part of SPHC to facilitate anticipatory symptom control in both groups. [ABSTRACT FROM AUTHOR]

Background: Individuals with migraine frequently experience pre- and post-headache symptoms. This analysis aimed to characterize the relative frequency and burden of pre- and post-headache symptoms in people with migraine using data collected through the Chronic Migraine Epidemiology and Outcomes – International Study. Methods: This cross-sectional, observational, web-based survey was conducted in 2021–2022 in Canada, France, Germany, Japan, the United Kingdom, and the United States. Respondents who met modified International Classification of Headache Disorders, 3rd edition, criteria were offered the opportunity to participate. Information collected included migraine-related disability, depression/anxiety symptoms, cutaneous allodynia, activity limitations, and acute treatment optimization. Respondents indicated how often they had pre- or post-headache symptoms using a 5-point scale, ranging from 0 to 4, with a rating of 2 or higher classified as a pre- or post-headache symptom case. Modeling was used to examine relationships with monthly headache days (MHDs) and activity limitations during pre-headache and post-headache phases. Results: Among a total of 14,492 respondents, pre-headache symptoms were reported by 66.9%, while post-headache symptoms were reported by 60.2%. Both pre-headache and post-headache symptoms were reported by 49.5% of respondents, only pre-headache by 17.4%, only post-headache by 10.7%, and neither pre- nor post-headache symptoms by 22.4%. Compared with respondents who experienced only pre- or post-headache symptoms, respondents who experienced both pre- and post-headache symptoms had the highest rates of 4–7, 8–14, and ≥ 15 monthly headache days (23.1%, 14.1%, and 10.9%, respectively). Of respondents with both pre- and post-headache symptoms, 58.5% reported moderate-to-severe disability, 47.7% reported clinically significant symptoms of depression, 49.0% reported clinically significant symptoms of anxiety, and 63.8% reported cutaneous allodynia with headache (ASC-12). Moderate-to-severe activity limitations were reported during the pre-headache (29.5%) and post-headache phases (27.2%). For all outcomes modeled, after controlling for covariates, having pre-headache symptoms, post-headache symptoms, or both were associated with worse outcomes than having neither. Conclusions: Pre- and post-headache phases of migraine are common, carry unrecognized burden, and may be a target for treatment. [ABSTRACT FROM AUTHOR]

Hyperostosis frontalis interna (HFI) is an osseous overgrowth characterized by symmetrical, irregular bone apposition on the internal table of the frontal bone, which preferentially occurs in females. In 1719, Morgagni described the condition as one sign of a triad comprising HFI, hirsutism, and obesity (Morgagni's syndrome). The etiopathogenesis of HFI is largely unresolved, but the condition is frequently associated with metabolic, endocrine, and neuropsychiatric disorders. In archaeological cases, which rely solely on dry bone diagnosis, the cause of HFI generally remains unknown, as is also the case regarding accompanying signs and symptoms. Here, we report a case of pronounced HFI in the skeleton of an old‐adult woman from medieval Hildesheim dating to the 8th to 11th century CE. In addition to HFI, the cranium exhibits resorptive lesions of the sella turcica with dehiscence of the roof of the sphenoid sinus. The co‐occurrence of these lesions suggests an underlying common cause for them. On the basis of differential diagnosis, we consider a functioning pituitary neuroendocrine tumor (PitNET) as the most likely common cause for the two conditions. [ABSTRACT FROM AUTHOR]

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Background: In patients with inflammatory bowel disease (IBD), a symptom with major impact on health-related quality of life is fatigue. To assess fatigue and conduct research regarding fatigue in IBD patients, a validated disease specific assessment tool is required. The aim of this study was to translate the Inflammatory Bowel Disease Fatigue patient self-assessment scale (IBD-F) into Dutch and to validate this translated scale in a Dutch IBD population. Methods: The study comprised three phases. In phase 1, the original IBD-F was translated into Dutch. Phase 2 comprised a pilot-test of the pre-final Dutch IBD-F to assess content validity by applying a semi-structured interview design. In phase 3, construct validity, internal consistency and test-retest reliability were assessed using a cross-sectional design. Results: Phase 1 resulted in the pre-final version of the Dutch IBD-F. After five semi-structured interviews with IBD patients in phase 2, minor adjustments were made which resulted in the final version of the Dutch IBD-F. Evaluation of this final version in 133 IBD patients showed adequate psychometric properties: good convergent validity with the Multidimensional Fatigue Inventory subscales (Spearman's r 0.57–0.86) and excellent internal consistency (Cronbach's alpha 0.94 for Section I and 0.97 for Section II). Test-retest reliability in 102 patients was shown to be good (Section I ICC 0.85 (95% CI 0.79–0.90) and Section II ICC 0.88 (95% CI 0.83–0.92)). Conclusions: The thorough translation process resulted in a comprehensible, valid and reliable version of the Dutch IBD-F. Convergent validity with the MFI-20 appeared to be good. This study found excellent internal consistency and good test-retest reliability. [ABSTRACT FROM AUTHOR]

Infectious diseases and their imperative awareness gain major relevance through global warming and multi-continent refugee crises. Here, we demonstrate the challenges of malaria diagnosis, disease course, and treatment, including post-artesunate hemolysis in a Syrian refugee with severe falciparum malaria, most probably infected during migrant smuggling from Türkiye to Germany. [ABSTRACT FROM AUTHOR]

Purpose: The worldwide mpox outbreak starting in May 2022 marks the occurrence of another previously atypical infectious disease in Europe. This study's objective was to present a comprehensive overview based on the gathered data and to illustrate the approach of the Cologne Health Department to contain the mpox outbreak. Methods: In this retrospective observational study, 368 individuals reported to the Cologne Health Department as PCR-positive for mpox were included. Data were collected in structured telephone interviews and digitally processed. Results: The first mpox case in Cologne was recorded on May 24, 2022. The local outbreak lasted approximately 4 months and reached its peak in July. The last reported case in Cologne occurred on September 17. Transmissions mostly occurred through sexual contacts (67.4%) or other close physical contacts (4.6%) between men, but also through fomites, in the context of events or occasionally in the work environment. In 21.5% of cases, no route of infection could be determined. The mean incubation period was 8.2 days. Clinically, mpox infections usually presented with skin and/or mucosal lesions accompanied by general symptoms. In 74.8% of cases, a prodromal stage was absent. Initially, the rash often had an unspecific appearance, but in the further clinical course, it usually passed through the typical stages. Most infections resolved spontaneously under home care. In 3.5% of cases, however, inpatient hospitalisation was required. Infected persons with a previous smallpox vaccination had 0.43 times the odds of unvaccinated persons to be affected by lesions in 3 or more body regions and 0.30 times the odds to develop lesions in all 5 body regions. Previous vaccination statistically reduced the total duration of symptoms by 2.0 days. Conclusions: The mpox outbreak 2022 in Cologne primarily affected men who have sex with men and have reported recent sexual encounters. The observed average incubation period was shorter than initially assumed. Mucosal involvement and associated symptoms occur in a relevant number of cases and can lead to more severe clinical courses. Previous smallpox vaccination was statistically significantly associated with milder courses of mpox. In the case of an unclear rash or symptoms suggesting mucosal involvement, mpox should be considered as a differential diagnosis. An equally rapid and well-orchestrated public health response are crucial for infection control. [ABSTRACT FROM AUTHOR]

Objective: Within the eleventh edition of the International Classification of Diseases (ICD‐11), diagnostic criteria for feeding and eating disorders were revised and new diagnoses including avoidant/restrictive food intake disorder (ARFID) are classifiable; however, nothing is known about how these changes affect the prevalence of feeding and eating disorders. This study compared the distribution and clinical characteristics of restrictive feeding and eating disorders between ICD‐10 and ICD‐11. Method: The Eating Disorder Examination (EDE), its child version, and the EDE ARFID module were administered to N = 82 patients (0–17 years) seeking treatment for restrictive feeding and eating disorders and their parents. Clinical characteristics were derived from medical records, questionnaires, and objective anthropometrics. Results: The number of residual restrictive eating disorders (rrED) significantly decreased from ICD‐10 to ICD‐11 due to a crossover to full‐threshold disorders, especially anorexia nervosa (AN) or ARFID. Patients reclassified to ICD‐11 ARFID were younger, had an earlier age of illness onset, more restrictive eating behaviors, and tended to have more somatic comorbidities compared to those reclassified to ICD‐11 AN. Patients with rrED according to both ICD‐10 and ICD‐11 were younger, had an earlier age of illness onset, less shape concern, and more somatic comorbidities than patients who were reclassified from ICD‐10 rrED to ICD‐11 AN or ARFID. Discussion: This study highlights the inclusive approach of ICD‐11 criteria, paving the way for more targeted treatment, and ARFID's high clinical relevance. Future studies considering nonrestrictive feeding and eating disorders across the life span may allow further analyses on diagnostic crossover. Public Significance: Changes in diagnostic criteria for restrictive eating disorders within the newly published ICD‐11 led to an increase in full‐threshold disorders, while the number of rrED was significantly lowered compared to ICD‐10 criteria. The results thus highlight the diagnostic utility of ICD‐11 criteria and may help providing adequate treatment to children and adolescents with rrED. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies that focused on socioeconomic differences did not comprehensively explain existing inequalities in psychosomatic rehabilitation in Germany. We applied a social milieu approach, which additionally includes sociocultural factors such as lifestyles, attitudes and values, to investigate differences among patients in symptom severity, psychosocial impairment and improvement over the course of the intervention. Methods: As a model for social milieus, the empirical Sinus milieus were used. 2,000 patients of two psychosomatic rehabilitation clinics in Germany were included and their milieu was assessed with the Sinus milieu indicator for Germany 10/2018 questionnaire. BDI-II (N  =  1,832) and HEALTH-49 (N  =  1,829) questionnaires were used to measure depressiveness and psychosocial impairment at admission (T0) and discharge after 5  weeks of treatment (T1). Milieu differences in severity and improvement were analyzed by mixed-model ANOVAs. Results: Milieu distribution was not representative of the overall population of Germany. We found significant differences between patients from different milieus in both BDI-II and HEALTH-49 (p  <  0.001). Patients from the Precarious Milieu had the highest burden of depressive symptoms in BDI-II and the highest impairment on all HEALTH-49 scales at T0 and T1. Over the course of rehabilitation, patients from all milieus improved significantly in all domains (p  <  0.001). Significant interaction effects showed milieu-dependent differences in improvement for depressiveness on the BDI-II [F(9, 1822)  =  2.50, p  =  0.008] and for three HEALTH-49 scales, namely Psychological well-being [F(9, 1819)  =  3.30, padj  =  0.005], Interactional difficulties [F(9, 1819)  =  2.74, padj  =  0.036] and Activity and Participation [F(9, 1819)  =  4.94, padj  <  0.001], while post-hoc tests only revealed two significant group differences for the last scale. In all domains, patients from the Precarious Milieu retained higher symptoms and impairment at T1 than patients from better-off milieus had at T0. Discussion: Social milieu was associated with symptom severity, treatment access and outcome of psychosomatic rehabilitation patients. Milieuspecific sociocultural habits, psychosocial needs and therapeutic demands may help describe differences and should be considered in therapy planning and implementation, to improve equal access, quality and effectiveness of rehabilitation. Therefore, further research on milieu-specific differences and needs is necessary. [ABSTRACT FROM AUTHOR]

Objective: Phenylketonuria (PKU) is a rare inherited metabolic disorder characterised by elevated phenylalanine (Phe) concentrations that can exert neurotoxic effects if untreated or upon treatment discontinuation. This systematic review supported by expert opinion aims to raise awareness among the neurological community on neurological complications experienced by adults with PKU (AwPKU). Methods: The PubMed database was searched for articles on neurological signs and symptoms in AwPKU published before March 2022. In addition, two virtual advisory boards were held with a panel of seven neurologists and two metabolic physicians from Germany and Austria. Findings are supported by three illustrative patient cases. Results: Thirty-nine articles were included. Despite early diagnosis and treatment, neurological signs and symptoms (e.g. ataxia, brisk tendon reflexes, tremor, visual impairment) can emerge in adulthood, especially if treatment has been discontinued after childhood. In PKU, late-onset neurological deficits often co-occur with cognitive impairment and psychiatric symptoms, all of which can be completely or partially reversed through resumption of treatment. Conclusion: Ideally, neurologists should be part of the PKU multidisciplinary team, either to bring lost to follow-up patients back to clinic or to manage symptoms in referred patients, considering that symptoms are often reversible upon regaining metabolic control. The current findings have been combined in a leaflet that will be disseminated among neurologists in Germany and Austria to create awareness. [ABSTRACT FROM AUTHOR]

The long-term outcome of connective tissue diseases is associated with the time from symptom onset to diagnosis. To understand gaps in care, we determine whether the length of time between symptom onset and first presentation to a rheumatologist has changed in Germany in recent decades. We analyzed data on patients diagnosed with connective tissue diseases (n = 19,662) collected from the German National Database of the Regional Cooperative Rheumatology Centers. We reviewed the onset of relevant symptoms listed at first presentations from 1993 to 2018 and performed a quantitative analysis of the intervals until first presentation to a rheumatologist. We compared time intervals and performed a linear mixed regression model with random effects to identify associated factors. Although the interval between the onset of symptoms and first presentation to a rheumatologist has diminished since 1980 for all connective tissue diseases, there has been no relevant improvement during the past 2 decades. The interval between symptoms and presentation increases with patients age for all connective tissue diseases (e.g., Systemic sclerosis; for each 10-year-increment of patients age: β 0.41, CI 0.38; 0.44). Among those diagnosed with systemic sclerosis, the mean interval was 1.5 years (95% CI 1.1; 1.8) for male patients and 2.6 years (95% CI 2.4; 2.8) for females. Patients presenting with different degrees of disease severity on their first visits and with different educational levels had similar mean intervals between symptoms and first presentation regardless of their final diagnoses. Over the past 2 decades, the time to first consultation with a rheumatologist has not continued to improve in Germany, but has stagnated at the same level. Selected patient subgroups, such as older patients with suspected connective tissue diseases and female patients with suspected systemic sclerosis, are at risk to present late and may in particular benefit from an earlier referral to a rheumatologist. [ABSTRACT FROM AUTHOR]

Background: Multisystemic Inflammatory Syndrome in children (MIS-C) is a rare autoimmune disorder occurring after a latency period following acute SARS-CoV-2 infection. The therapeutic regime of MIS-C is adapted to the therapy of the Kawasaki disease, as clinical symptoms are similar. Since the Kawasaki disease can potentially result in severe symptoms, which may even affect long-term health, it is essential to gain further knowledge about MIS-C. Thus, we aimed to investigate the incidence, symptoms, therapeutical procedure and outcome of MIS-C patients in the metropolitan area of Nuremberg-Erlangen during the SARS-CoV2 pandemic. Material and Methods: Retrospective analysis of clinical charts of MIS-C patients was carried out at three children's hospitals covering the medical care of the metropolitan area of Nuremberg-Erlangen in Germany. Demographic characteristics and symptoms at first visit, their clinical course, therapeutic regime and outcome were recorded within the time period January 2021–December 2022. Results: Analysis of 10 patients (5 male, 5 female) with MIS-C resulting in an incidence of 2.14/100.000 children. The median time between COVID-19 infection and admission to hospital was 5 weeks. The median age was 7 years. Symptoms comprised fever (100%), rash (70%), bilateral non-purulent conjunctivitis (70%) and urticaria (20%). At the time of presentation, diagnosis-defining inflammation parameters were increased and the range for C-reactive protein was 4.13 mg/dL to 28 mg/dL, with a median of 24.7 mg/dL. Procalcitonin was initially determined in six patients (1.92 ng/mL to 21.5 ng/mL) with a median value of 5.5 pg/mL. Two patients displayed leukocytosis and two displayed leukopenia. None of the patients presented coronary pathologies. Nine of the ten patients received intravenous immunoglobulin (IVIG) therapy. In addition, patients received intravenous steroids (80%) and acetylsalicylic acid (80%). Conclusion: SARS-CoV virus may rarely exert multiorgan manifestations due to hyperinflammatory immunological processes. Within two years of the COVID-19 pandemic, we identified ten patients with COVID-induced MIS-C in the metropolitan area Nuremberg-Erlangen. In the description of the patient collective, we can confirm that MIS-C is distinguished from the Kawasaki disease by the lack of coronary manifestations. Interestingly, although having monitored all pediatric facilities in the investigated area, we find lower incidences of MIS-C compared to findings in the literature. In conclusion, an overestimation of incidences in the upcoming MIS-C during the pandemic needs to be considered. [ABSTRACT FROM AUTHOR]

Purpose: The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has caused substantial mortality worldwide. We investigated clinical and demographic features of COVID-19-related deaths that occurred between March 2020 and January 2022 in Regensburg, Germany. Methods: We compared data across four consecutive time periods: March 2020 to September 2020 (period 1), October 2020 to February 2021 (period 2), March 2021 to August 2021 (period 3), and September 2021 to January 2022 (period 4). Results: Overall, 405 deaths in relation to COVID-19 were reported. The raw case fatality ratio (CFR) was 0.92. In periods 1 to 4, the CFRs were 1.70%, 2.67%, 1.06%, and 0.36%. The age-specific CFR and mortality were highest in persons aged ≥ 80 years in period 2 while mortality in younger cases increased with time. The median age at death was 84 years and it varied slightly across periods. Around 50% of cases of death were previously hospitalized. In all time periods, the cause of death was mostly attributed to COVID-19. Over the four periods, we did not find significant changes in the distribution of sex and risk factors for severe disease. The most frequent risk factor was cardio-circulatory disease. Conclusion: In conclusion, the CFR decreased over time, most prominently for period 4. Mortality was considerable and younger cases were increasingly at risk. [ABSTRACT FROM AUTHOR]