Clinical Features and Voxel-Based-Symptom-Lesion Mapping of Silent Aspiration in Acute Infratentorial Stroke.

Post-stroke dysphagia (PSD) is a severe and common complication after ischemic stroke. The role of silent aspiration as an important contributing factor in the development of a dysphagia-associated complications, in particular aspiration-associated pneumonia has been insufficiently understood. The aim of this study was to investigate the characteristics and risk factors of silent aspiration in patients with acute infratentorial stroke by FEES and to identify culprit lesions in stroke patient with a high risk of silent aspiration via voxel-based-symptom-lesion mapping (VBS/ML). This study is a retrospective observational study based on a prospectively collected FEES and stroke database. Consecutive patient cases with acute ischemic infratentorial stroke and FEES examination between 2017 and 2022 were identified. Group allocation was performed based on PAS scores. Imaging analysis was performed by manual assignment and by VBS/ML. Group comparisons were performed to assess silent aspiration characteristics. Binary logistic regression analysis was performed to determine if baseline clinical, demographic, and imaging parameters were helpful in predicting silent aspiration in patients. In this study 84 patient cases with acute infratentorial stroke who underwent FEES examination were included. Patients were moderately affected at admission (mean NIH-SS score at admission 5.7 SD ± 4.7). Most lesions were found pontine. Overall 40.5% of patients suffered from silent aspiration, most frequently in case of bilateral lesions. Patients with silent aspiration had higher NIH-SS scores at admission (p < 0.05), had a more severe swallowing disorder (p < 0.05) and were 4.7 times more likely to develop post-stroke pneumonia. Patients who underwent FEES examination later than 72 h after symptom onset were significantly more likely to suffer from silent aspiration and to develop pneumonia compared to patients who underwent FEES examination within the first 72 h (p < 0.05). A binary logistic regression model identified NIH-SS at admission as a weak predictor of silent aspiration. Neither in manual assignment of the lesions to brain regions nor in voxel-wise statistic regression any specific region was useful in prediction of silent aspiration. Silent aspiration is common in patients with infratentorial stroke and contributes to the risk for pneumonia. Patients with silent aspiration are more severely affected by stroke, but cannot reliably be identified by NIH-SS at admission or lesion location. Patients suffering from acute infratentorial stroke should been screened and examined for PSD and silent aspiration.

Shedding light on the clinical recognition process of transient global amnesia.

BACKGROUND AND PURPOSE: Diagnostic uncertainty is common in the emergency evaluation of neurological conditions such as acute confusional states, particularly for non-neurologists. We aimed to investigate the clinical recognition process of transient global amnesia (TGA) before arrival at the hospital and in the emergency department (ED). METHODS: In this retrospective observational study, medical records of 365 patients with TGA were analysed concerning mode of arrival, symptoms and suspected diagnosis made by pre-hospital medical care providers and the ED neurologist. RESULTS: More than half of the 248 patients who were evaluated before arrival at the hospital (N = 157, 63.3%) received a diagnosis of suspected stroke, whereas TGA was considered in only 16 patients (6.5%), with recognition of acute amnesia in 150 patients (60.5%) and disturbed orientation in 86 patients (34.7%). Repetitive questions by the patient were noted in 28 patients (11.3%). In contrast, in 355 patients (97.3%), TGA was considered the primary diagnosis by the ED neurologist. Diagnosis in the ED was achieved by documenting ongoing impairment of episodic verbal memory (100.0%), repetitive questions as a prominent ancillary finding (95.5%) and the lack of focal neurological symptoms (100.0%) or by carefully obtaining collateral history suggestive of anterograde memory disturbance (89.9%) and/or repetitive questions (85.7%). CONCLUSION: Recognizing TGA crucially depends on identifying isolated anterograde episodic long-term memory disturbance or its observable effects such as repetitive questions and actions.

Use of analgesics in acute stroke patients with inability to self-report pain: a retrospective cohort study.

BACKGROUND: Pain is a common and burdensome complication in patients with acute stroke. We assessed the impact of impaired communication in stroke patients on pain assessment and treatment. METHODS: We included 909 (507 male, mean age 71.8 years) patients admitted to our stroke unit from 01/2015 to 12/2015 in the analysis. Patients were assigned to four groups: able to communicate (AC), not able to communicate prior to index stroke (P-NAC), due to focal symptoms of index stroke (S-NAC), due to a reduced level of consciousness (C-NAC). Pain prevalence, documentation of pain and use of analgesics were evaluated. C-NAC patients were excluded from analyses regarding analgesic treatment due to relevant differences in patient characteristics. RESULTS: 746 patients (82.1%) were classified as AC, 25 (2.8%) as P-NAC, 90 (9.9%) as S-NAC and 48 (5.3%) as C-NAC. Pain was documented on the Numeric Rating Scale and in form of free text by nurses and physicians. Nurses documented pain more frequently than physicians (p < 0.001). Pain prevalence was 47.0% (n.s. between groups). The use of analgesic medication increased from 48.7% in the AC group, to 76.0% in the P-NAC group, and 77.8% in the S-NAC group (p < 0.001). Opioid use was significantly more frequent in NAC patients (p < 0.001). The response to the treatment was poorly documented with significantly lowest rates in S-NAC patients (p < 0.001). CONCLUSIONS: Our study suggests that post-stroke pain in patients with inability to communicate is not attended enough, not systematically assessed and therefore not sufficiently treated.

Drp1/Fis1-mediated mitochondrial fragmentation leads to lysosomal dysfunction in cardiac models of Huntington's disease.

Huntington's disease (HD) is a fatal hereditary neurodegenerative disorder, best known for its clinical triad of progressive motor impairment, cognitive deficits and psychiatric disturbances, is caused by CAG-repeat expansion in exon 1 of Huntingtin (HTT). However, in addition to the neurological disease, mutant HTT (mHTT), which is ubiquitously expressed in all tissues, impairs other organ systems. Not surprisingly, cardiovascular dysautonomia as well as the deterioration of circadian rhythms are among the earliest detectable pathophysiological changes in individuals with HD. Mitochondrial dysfunction in the brain and skeletal muscle in HD has been well documented, as the disease progresses. However, not much is known about mitochondrial abnormalities in the heart. In this study, we describe a role for Drp1/Fis1-mediated excessive mitochondrial fission and dysfunction, associated with lysosomal dysfunction in H9C2 expressing long polyglutamine repeat (Q73) and in human iPSC-derived cardiomyocytes transfected with Q77. Expression of long polyglutamine repeat led to reduced ATP production and mitochondrial fragmentation. We observed an increased accumulation of damaged mitochondria in the lysosome that was coupled with lysosomal dysfunction. Importantly, reducing Drp1/Fis1-mediated mitochondrial damage significantly improved mitochondrial function and cell survival. Finally, reducing Fis1-mediated Drp1 recruitment to the mitochondria, using the selective inhibitor of this interaction, P110, improved mitochondrial structure in the cardiac tissue of R6/2 mice. We suggest that drugs focusing on the central nervous system will not address mitochondrial function across all organs, and therefore will not be a sufficient strategy to treat or slow down HD disease progression.

[Pilot study on drinking and voiding management in child day-care facilities in the district of Garmisch-Partenkirchen]. / Pilotstudie zum Trink- und Entleerungsmanagement in Kindertagesbetreuungseinrichtungen im Landkreis Garmisch-Partenkirchen.

BACKGROUND AND OBJECTIVES: The development of child day care is currently the focus of a public discussion. More and more very young children are cared for in a day-care facility rather than by the family. Therefore, key aspects of education are shifted into these institutions. The aim of this survey was to inquire about the current situation of drinking and voiding management in day-care facilities in the district of Garmisch-Partenkirchen. MATERIALS AND METHODS: In all, 322 questionnaires were sent to employees of 40 child day-care facilities. Organization of drinking and voiding behavior advices and personal assessments of continence education were queried. The evaluation was carried out anonymously. RESULTS: A total of 29 facilities (73%) replied. The average fluid intake was 260 ml (50-750 ml) at 12 o'clock in all day-care facilities included. The possibility to decide when to have breakfast and when to drink according to the individual thirst is practised in 43% (62/143) of the facilities. A fixed amount of fluid intake was offered by 11% (16/150) of the institutions. Of those responding, 92% (139/151) specifically send the children to the toilet, while 85% of the participants consider a continence education concept would be useful. CONCLUSION: According to a general trend, children attend day-care facilities earlier and spend more time there. This means that educational staff are taking care of children who are not yet continent. A verifiable continence educational concept does not exist in any of the institutions surveyed; however, most participants would favor such a concept. It would be desirable to establish an interprofessional health education program in which drinking and voiding training is integrated according to national recommendations.

Using Patient-Derived Induced Pluripotent Stem Cells to Identify Parkinson's Disease-Relevant Phenotypes.

PURPOSE OF REVIEW: Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting older individuals. The specific cause underlying dopaminergic (DA) neuron loss in the substantia nigra, a pathological hallmark of PD, remains elusive. Here, we highlight peer-reviewed reports using induced pluripotent stem cells (iPSCs) to model PD in vitro and discuss the potential disease-relevant phenotypes that may lead to a better understanding of PD etiology. Benefits of iPSCs are that they retain the genetic background of the donor individual and can be differentiated into specialized neurons to facilitate disease modeling. RECENT FINDINGS: Mitochondrial dysfunction, oxidative stress, ER stress, and alpha-synuclein accumulation are common phenotypes observed in PD iPSC-derived neurons. New culturing technologies, such as directed reprogramming and midbrain organoids, offer innovative ways of investigating intraneuronal mechanisms of PD pathology. PD patient-derived iPSCs are an evolving resource to understand PD pathology and identify therapeutic targets.

CyberKnife® fixed cone and Iris™ defined small radiation fields: Assessment with a high-resolution solid-state detector array.

PURPOSE: The challenges of accurate dosimetry for stereotactic radiotherapy (SRT) with small unflattened radiation fields have been widely reported in the literature. In this case, suitable dosimeters would have to offer a submillimeter spatial resolution. The CyberKnife® (Accuray Inc., Sunnyvale, CA, USA) is an SRT-dedicated linear accelerator (linac), which can deliver treatments with submillimeter positional accuracy using circular fields. Beams are delivered with the desired field size using fixed cones, the InCise™ multileaf collimator or a dynamic variable-aperture Iris™ collimator. The latter, allowing for field sizes to be varied during treatment delivery, has the potential to decrease treatment time, but its reproducibility in terms of output factors (OFs) and dose profiles (DPs) needs to be verified. METHODS: A 2D monolithic silicon array detector, the "Octa", was evaluated for dosimetric quality assurance (QA) for a CyberKnife system. OFs, DPs, percentage depth-dose (PDD) and tissue maximum ratio (TMR) were investigated, and results were benchmarked against the PTW SRS diode. Cross-plane, in-plane and 2 diagonal dose profiles were measured simultaneously with high spatial resolution (0.3 mm). Monte Carlo (MC) simulations with a GEANT4 (GEometry ANd Tracking 4) tool-kit were added to the study to support the experimental characterization of the detector response. RESULTS: For fixed cones and the Iris, for all field sizes investigated in the range between 5 and 60 mm diameter, OFs, PDDs, TMRs, and DPs in terms of FWHM measured by the Octa were accurate within 3% when benchmarked against the SRS diode and MC calculations. CONCLUSIONS: The Octa was shown to be an accurate dosimeter for measurements with a 6 MV FFF beam delivered with a CyberKnife system. The detector enabled real-time dosimetric verification for the variable aperture Iris collimator, yielding OFs and DPs consistent with those obtained with alternative methods.

[The German research network CURE-Net : A benefit for patients with rare diseases]. / Das deutsche Forschungsnetzwerk CURE-Net : Ein Gewinn für Patienten mit seltenen Erkrankungen.

With the help of the media, there is growing public awareness for the problems associated with rare diseases and their impact on the lives of those affected and their families. Bladder exstrophy-epispadias complex (BEEC) is also a part of the group of rare diseases within the urological field. The German network CURE-Net was founded in 2009 to systematically collect data regarding the epidemiological and molecular causes, and clinical and psychosocial effects of congenital urorectal malformations. With the help of self-help groups a national registry could be established for systematic data retrieval. This research can help to improve existing medical care and follow-up for affected individuals with BEEC.

Blood-CSF-barrier dysfunction is a marker for encephalitic involvement in patients with aseptic meningitis/meningoencephalitis.

BACKGROUND: The term "aseptic meningitis" encompasses cases of meningitis with negative bacterial CSF culture, which predominantly are of viral etiology. While the clinical course is usually benign, complications such as encephalitic involvement resulting in a more severe clinical course may occur. Dysfunction of the blood-brain-barrier (BBB), which is a prerequisite for viral entry into the brain parenchyma, can be approximated using the CSF/serum albumin ratio, readily obtainable in routine CSF analysis. OBJECITVES: Analysis of CSF patterns in patients with aseptic meningitis/meningoencephalitis with a focus on BBB dysfunction as a marker for encephalitic involvement. STUDY DESIGN: Retrospective chart review of patients admitted to our hospital between 2004 and 2016 with a diagnosis of aseptic meningitis/meningoencephalitis. RESULTS: Patients with aseptic meningitis displaying clinical, MR-tomographic or electroencephalographic signs of encephalitic involvement were significantly older than patients without these features (47.4 vs. 35.5 yrs., p=0.002). In patients with meningoencephalitis, CSF analysis revealed a more severe disruption of BBB, approximated by the CSF/serum albumin ratio (p=0.002). Compromised BBB function correlated positively with length of hospitalization (p=0.007), indicative of a more severe clinical course. The number of CSF lymphocytes was found to predict the severity of the BBB disruption, which additionally was more frequently observed when herpesviridae were identified as infectious agents. CONCLUSIONS: We suggest that the CSF/serum albumin ratio as an estimate for BBB function should be attended to in the evaluation of patients with aseptic meningitis. Severe BBB dysfunction, older age and infection with herpesviridae appear to raise the risk for encephalitic involvement.

Anterior Cruciate Ligament Reconstruction - Does the Surgeon Risk Worsening of the Clinical Outcome During the Learning Curve if He Switches from Single Bundle Technique to Double Bundle Technique?

Background: Anatomical reconstruction of the anterior cruciate ligament (ACL) using the double-bundle (DB) technique is becoming increasingly popular. Despite its proved biomechanical and anatomical superiority, clinical studies have found little advantage for the DB technique. The aim of this study was therefore to evaluate whether an experienced surgeon is able to obtain his usual good results with ACL reconstruction with the single-bundle (SB) technique directly after changing to the DB technique. Patients/Material and Methods: In a prospective, non-randomised and controlled interventional study, we compared the first 19 patients in our clinic who had an anterior cruciate ligament reconstruction using the DB technique with 31 patients who underwent a SB ACL reconstruction performed by the same surgeon during the same period of investigation. The visual analog scale (VAS) for pain and function, the Tegner activity score, the International Knee Documentation Committee (IKDC), the Lysholm and the Marshall scores were used as evaluation methods, the anterior stability (KT-1000-arthrometer measurement) and the deficits in muscle strength in extension and flexion of both knees were measured in a standard manner one year after operation. Results: The Lysholm scores in the SB group (93.6 [± 3.8] points) and in the DB group (93.1 [± 4.2] points) were not significantly different (p > 0.05). Neither the VAS for pain (1 [± 2] points for both techniques), nor the VAS for function (8 [± 2] versus 7 [± 2] points) were significantly different (p > 0.05). For the anterior stability under Maximum Measurement Displacement (MMD), the SB group achieved a difference of 1.75 (± 1.94) mm, in comparison with 1.32 (± 1.89) mm for the DB group (p > 0.05). There was a trend to less deficit in muscle strength after DB ACL reconstruction. No complications were recorded in either group. Conclusion: Experienced surgeons in ACL reconstruction can change from the popular SB ACL reconstruction to the DB ACL reconstruction without causing clinical problems or additional complications. The well-known good results of the DB technique were attained in the first operations performed by an experienced surgeon and are compareable to the results of the SB technique.

Consensus on Recording Deep Endometriosis Surgery: the CORDES statement.

STUDY QUESTION: Which essential items should be recorded before, during and after endometriosis surgery and in clinical outcome based surgical trials in patients with deep endometriosis (DE)? SUMMARY ANSWER: A DE surgical sheet (DESS) was developed for standardized reporting of the surgical treatment of DE and an international expert consensus proposal on relevant items that should be recorded in surgical outcome trials in women with DE. WHAT IS KNOWN ALREADY: Surgery is an important treatment for symptomatic DE. So far, data have been reported in such a way that comparison of different surgical techniques is impossible. Therefore, we present an international expert proposal for standardized reporting of surgical treatment and surgical outcome trials in women with DE. STUDY DESIGN, SIZE, DURATION: International expert consensus based on a systematic review of literature. PARTICIPANTS/MATERIALS, SETTING, METHODS: Taking into account recommendations from Consolidated Standards of Reporting Trials (CONSORT), the Innovation Development Exploration Assessment and Long-term Study (IDEAL), the Initiative on Methods, Measurement and Pain Assessment in Clinical trials (IMMPACT) and the World Endometriosis Research Foundation Phenome and Biobanking Harmonisation Project (WERF EPHect), a systematic literature review on surgical treatment of DE was performed and resulted in a proposal for standardized reporting, adapted by contributions from eight members of the multidisciplinary Leuven University Hospitals Endometriosis Care Program, from 18 international experts and from audience feedback during three international meetings. MAIN RESULTS AND THE ROLE OF CHANCE: We have developed the DESS to record in detail the surgical procedures for DE, and an international consensus on pre-, intra- and post-operative data that should be recorded in surgical outcome trials on DE. LIMITATIONS, REASONS FOR CAUTION: The recommendations in this paper represent a consensus among international experts based on a systematic review of the literature. For several items and recommendations, high-quality RCTs were not available. Further research is needed to validate and evaluate the recommendations presented here. WIDER IMPLICATIONS OF THE FINDINGS: This international expert consensus for standardized reporting of surgical treatment in women with DE, based on a systematic literature review and international consensus, can be used as a guideline to record and report surgical management of patients with DE and as a guideline to design, execute, interpret and compare clinical trials in this patient population. STUDY FUNDING/COMPETING INTERESTS: None of the authors received funding for the development of this paper. M.A. reports personal fees and non-financial support from Bayer Pharma outside the submitted work; H.T. reports a grant from Pfizer and personal fees for being on the advisory board of Perrigo, Abbvie, Allergan and SPD. TRIAL REGISTRATION NUMBER: N/A.

PU.1 cooperates with IRF4 and IRF8 to suppress pre-B-cell leukemia.

The Ets family transcription factor PU.1 and the interferon regulatory factor (IRF)4 and IRF8 regulate gene expression by binding to composite DNA sequences known as Ets/interferon consensus elements. Although all three factors are expressed from the onset of B-cell development, single deficiency of these factors in B-cell progenitors only mildly impacts on bone marrow B lymphopoiesis. Here we tested whether PU.1 cooperates with IRF factors in regulating early B-cell development. Lack of PU.1 and IRF4 resulted in a partial block in development the pre-B-cell stage. The combined deletion of PU.1 and IRF8 reduced recirculating B-cell numbers. Strikingly, all PU.1/IRF4 and ~50% of PU.1/IRF8 double deficient mice developed pre-B-cell acute lymphoblastic leukemia (B-ALL) associated with reduced expression of the established B-lineage tumor suppressor genes, Ikaros and Spi-B. These genes are directly regulated by PU.1/IRF4/IRF8, and restoration of Ikaros or Spi-B expression inhibited leukemic cell growth. In summary, we demonstrate that PU.1, IRF4 and IRF8 cooperate to regulate early B-cell development and to prevent pre-B-ALL formation.

Gestational and Non-gestational Trophoblastic Disease. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry No. 032/049, December 2015).

Purpose: The aim was to establish an official interdisciplinary guideline, published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). The guideline was developed for use in German-speaking countries. In addition to the Germany Society of Gynecology and Obstetrics, the guideline has also been approved by the Swiss Society of Gynecology and Obstetrics (SGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). The aim was to standardize diagnostic procedures and the management of gestational and non-gestational trophoblastic disease in accordance with the principles of evidence-based medicine, drawing on the current literature and the experience of the colleagues involved in compiling the guideline. Methods: This s2k guideline represents the consensus of a representative panel of experts with a range of different professional backgrounds commissioned by the DGGG. Following a review of the international literature and international guidelines on trophoblastic tumors, a structural consensus was achieved in a formalized, multi-step procedure. This was done using uniform definitions, objective assessments, and standardized management protocols. Recommendations: The recommendations of the guideline cover the epidemiology, classification and staging of trophoblastic tumors; the measurement of human chorionic gonadotropin (hCG) levels in serum, and the diagnosis, management, and follow-up of villous trophoblastic tumors (e.g., partial mole, hydatidiform mole, invasive mole) and non-villous trophoblastic tumors (placental site nodule, exaggerated placental site, placental site tumor, epitheloid trophoblastic tumor, and choriocarcinoma).

[Epispadias and urethral duplication]. / Epispadie und Harnröhrenduplikatur.

Epispadias is the mildest form of the exstrophy-epispadias complex and rarely occurs in an isolated form. The characteristic clinical sign is a mucosal strip on the penile dorsum. Clinically, epispadias presents with urinary incontinence. Primary surgical correction is recommended at the age of 12 months and should only be performed at a specialized center. During follow-up, further bladder neck surgery may be necessary. Despite a functional and cosmetically appealing penis, psychosocial and psychosexual development of the affected individuals can severely be affected. The incidence of urethral duplication remains unclear. Several classifications reflect the anatomical variation. The clinical presentation depends on the continuity of the duplicated urethra and its relationship to the sphincteric mechanism. In addition to clinical examination, a voiding cysturethrography is part of the basic diagnostic workup. After endoscopic examination an individual operative approach can be defined.

Whole-body SPECT/CT for bone scintigraphy: diagnostic value and effect on patient management in oncological patients.

PURPOSE: This study was designed to assess the additional value of SPECT/CT of the trunk used in conjunction with conventional nuclear imaging and its effects on patient management in a large patient series. METHODS: In 353 patients, whole-body scintigraphy (WBS), SPECT, and SPECT/CT were prospectively performed for staging and restaging. SPECT/CT of the trunk was performed in all patients. In the 308 evaluable patients (211 with breast cancer, 97 with prostate cancer), clinical follow-up was used as the gold standard. Bone metastases were confirmed in 72 patients and excluded in 236. Multistep analyses per lesion and per patient were performed. Clinical relevance was expressed in terms of downstaging and upstaging rates on a per-patient basis. RESULTS: In the total patient group, sensitivities, specificities, and negative and positive predictive values on a per-patient basis were 93 %, 78 %, 95 % and 59 % for WBS, 94 %, 71 %, 97 % and 53 % for SPECT, and 97 %, 94 %, 97 % and 88 % for SPECT/CT, respectively. In all subgroups, specificity and positive predictive value were significantly (p<0.01) better with SPECT/CT. Downstaging of metastatic disease in the total, breast cancer and prostate cancer groups using SPECT/CT was possible in 32.1 %, 33.8 % and 29.5 % of patients, respectively. Upstaging in previously negative patients by additional SPECT/CT was observed in three breast cancer patients (2.1 %). Further diagnostic imaging procedures for unclear scintigraphic findings were necessary in only 2.5 % of patients. SPECT/CT improved diagnostic accuracy for defining the extent of multifocal metastatic disease in 34.6 % of these patients. CONCLUSIONS: SPECT/CT significantly improved the specificity and positive predictive value of bone scintigraphy in cancer patients. In breast cancer patients, we found a slight increase in sensitivity. SPECT/CT had a significant effect on clinical management because of correct downstaging and upstaging, better definition of the extent of metastases, and a reduction in further diagnostic procedures.