Epidermolysis bullosa acquisita (EBA) and acquired hemophilia A (AHA) are two rare autoimmune disorders. Respectively, EBA is an autoimmune blistering disease (AIBD) of the skin and mucous membranes, elicited by IgG autoantibodies against the collagen VII protein, a constituent of the dermal-epidermal junction (DEJ).1,2 Acquired hemophilia A instead is caused by circulating IgG antibodies against factor V and represents a potentially lethal disease because of the elevated risk of hemorrhages.

Introduction : Cytomegalovirus (CMV)-infection and reactivation remain a relevant complication after liver transplantation (LT). The recipient and donor serum CMV-IgG-status has been established for risk stratification when choosing various pharmaceutical regimens for CMV-prophylaxis in the last two decades. However, factors influencing course of CMV-infection in LT remain largely unknown. In this study, the impact of immunosuppressive regimen was examined in a large cohort of patients. Methods: All patients that underwent primary LT between 2006 and 2018 at the Charite-Universitaetsmedizin, Berlin, were included. Clinical course as well as histological and laboratory findings of patients were analyzed our prospectively maintained database. Univariate and multivariate regression analysis for impact of variables on CMV-occurrence was conducted, and survival was examined using Kaplan-Meier analysis. Results: Overall, 867 patients were included in the final analysis. CMV-infection was diagnosed in 325 (37.5%) patients after transplantation. Significantly improved overall survival was observed in these patients (Log rank = 0.03). As shown by correlation and regression tree classification and regression tree analysis, the recipient/donor CMV-IgG-status with either positivity had the largest influence on CMV-occurrence. Analysis of immunosuppressive burden did not reveal statistical impact on CMV-infection, but statistically significant inverse correlation of cumulative tacrolimus trough levels and survival was found (Log rank < .001). Multivariate analysis confirmed these findings (p = .02). Discussion; CMV-infection remains of clinical importance after LT. Undergone CMV-infection of either recipient or donor requires prophylactic treatment. Additionally, we found a highly significant, dosage-dependent impact of immunosuppression (IS) on long-term outcomes for these patients, underlying the importance of minimization of IS in liver transplant recipients.

Heart failure (HF) is a major disease in our society that often presents with multiple comorbidities with mutual interaction and aggravation. The comorbidity of HF and stroke is a high risk condition that requires particular attention to ensure early detection of complications, efficient diagnostic workup, close monitoring, and consequent treatment of the patient. The bi-directional interaction between the heart and the brain is inherent in the pathophysiology of HF where HF may be causal for acute cerebral injury, and - in turn - acute cerebral injury may induce or aggravate HF via imbalanced neural and neurovegetative control of cardiovascular regulation. The present document represents the consensus view of the ESC Council on Stroke, the Heart Failure Association and the ESC Working Group on Thrombosis to summarize current insights on pathophysiological interactions of the heart and the brain in the comorbidity of HF and stroke. Principal aspects of diagnostic workup, pathophysiological mechanisms, complications, clinical management in acute conditions and in long-term care of patients with the comorbidity are presented and state-of-the-art clinical management and current evidence from clinical trials is discussed. Beside the physicians perspective, also the patients values and preferences are taken into account. Interdisciplinary cooperation of cardiologists, stroke specialists, other specialists and primary care physicians is pivotal to ensure optimal treatment in acute events and in continued long-term treatment of these patients. Key consensus statements are presented in a concise overview on mechanistic insights, diagnostic workup, prevention and treatment to inform clinical acute and continued care of patients with the comorbidity of HF and stroke.

Aims: To explore international undergraduate pharmacy students' views on integrating artificial intelligence (AI) into pharmacy education and practice. Methods: This cross-sectional institutional review board-approved multinational, multicentre study comprised an anonymous online survey of 14 multiple-choice items to assess pharmacy students' preferences for AI events in the pharmacy curriculum, the current state of AI education, and students' AI knowledge and attitudes towards using AI in the pharmacy profession, supplemented by 8 demographic queries. Subgroup analyses were performed considering sex, study year, tech-savviness, and prior AI knowledge and AI events in the curriculum using the Mann-Whitney U-test. Variances were reported for responses in Likert scale format. Results: The survey gathered 387 pharmacy student opinions across 16 faculties and 12 countries. Students showed predominantly positive attitudes towards AI in medicine (58%, n = 225) and expressed a strong desire for more AI education (72%, n = 276). However, they reported limited general knowledge of AI (63%, n = 242) and felt inadequately prepared to use AI in their future careers (51%, n = 197). Male students showed more positive attitudes towards increasing efficiency through AI (P = .011), while tech-savvy and advanced-year students expressed heightened concerns about potential legal and ethical issues related to AI (P < .001/P = .025, respectively). Students who had AI courses as part of their studies reported better AI knowledge (P < .001) and felt more prepared to apply it professionally (P < .001). Conclusions: Our findings underline the generally positive attitude of international pharmacy students towards AI application in medicine and highlight the necessity for a greater emphasis on AI education within pharmacy curricula.

Non-biologic immunosuppressive drugs, such as azathioprine, dapsone or methotrexate are fundamental treatment options for a wide range of autoimmune and chronic inflammatory skin diseases. Some of these drugs were initially used for malignancies (e.g., azathioprine or methotrexate) or infectious diseases (e.g., hydroxychloroquine or dapsone) but are nowadays mostly used for their immunosuppressive/immunomodulating action. Although dermatologists have years of clinical experience with these drugs, some of the mechanisms of action are not fully understood and are the subject of research. Although these drugs are commonly used, lack of experience or knowledge regarding their safety profiles and management leads to skepticism among physicians. Here, we summarize the mechanism of action and detailed management of adverse effects of the most commonly used immunosuppressive drugs for skin diseases. Furthermore, we discuss the management of these drugs during pregnancy and breastfeeding, as well as their interaction and handling during vaccination.

Objective: Levetiracetam is increasingly used in pregnant women with epilepsy. Although teratogenic effects have not been observed so far, data on the risks of spontaneous abortion and major birth defects are still limited, especially for the frequently used dual therapy of levetiracetam and lamotrigine. Our primary aim was to analyze rates of major birth defects and spontaneous abortion after maternal levetiracetam treatment.Methods: This was a cohort study based on pregnancies recorded by the Embryotox Center from 2000 to 2017. Outcomes of prospectively ascertained pregnancies with first trimester levetiracetam monotherapy (n = 221) were compared to pregnancies with lamotrigine monotherapy for epilepsy (n = 469). In addition, all pregnancies with levetiracetam (n = 364) exposure during the first trimester were analyzed in comparison to a nonexposed cohort (n = 729). Pregnancies with the most frequently used combination therapy comprising levetiracetam and lamotrigine (n = 80) were evaluated separately.Results: There was no significantly increased risk of major birth defects or of spontaneous abortions after first trimester exposure to levetiracetam. Birth weight of male neonates was significantly lower after levetiracetam monotherapy compared to lamotrigine monotherapy. Dual therapy with levetiracetam and lamotrigine resulted in a significantly increased risk of spontaneous abortion (adjusted hazard ratio = 3.01, 95% confidence interval [CI] = 1.43-6.33) and a nonsignificant effect estimate for major birth defects (7.7%, n = 5/65, adjusted odds ratio = 1.47, 95% CI = .48-4.47) compared to a nonexposed cohort.Significance: Our study confirms the use of levetiracetam as a suitable antiepileptic drug in pregnancy. The lower birth weight of male neonates after maternal levetiracetam monotherapy and the unexpectedly high risk of spontaneous abortion and birth defects after dual therapy with levetiracetam and lamotrigine require further investigation.

Objectives: Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) are spreading globally. However, respective data from African communities including livestock and environmental specimens are rare. In a rural community of southern Rwanda, we assessed intestinal carriage of ESBL-PE among residents and livestock as well as presence in household specimens and examined associated factors. Methods: Samples of humans and livestock (both rectal swabs), soil, water, vegetables and animal products were collected within 312 community households in Sovu, Southern Rwanda. Specimens were screened for ESBL-PE on chromogenic agar, and susceptibility to common antibiotics was determined by disc diffusion assays. Socio-demographic information was collected with questionnaires focusing on the socio-economic background, alimentation, living conditions, hygiene measures and medical history of the participants. Results: Data and specimens from 312 randomly selected households including 617 human beings, 620 livestock and of approximately each 300 kitchen vegetables, animal products, soil and drinking water were analysed. Overall, 14.8% of 2508 collected samples were positive for ESBL-PE; figures were highest for humans (37.9%) and livestock (15.6%), lower for vegetables (3.8%) and animal products (3.3%), and lowest for soil (1.6%) and water (0.6%). Most detected ESBL-PE were Escherichia coli (93.5%) in addition to Klebsiella pneumoniae (6.5%). Cross-resistance to ampicillin-sulbactam, ciprofloxacin and co-trimoxazole was common. Logistic regression identified increasing age, another ESBL-PE positive household member, prolonged time for fetching water, current diarrhoea and the ability to pay school fees as independent predictors of intestinal ESBL-PE carriage among community members. Conclusions: ESBL-PE carriage is common in a rural Rwandan farming community. Carriage in livestock is not associated with human carriage. Associated factors suggest few addressable risk factors. The data indicate that in southern Rwanda, ESBL-PE are no longer primarily hospital-based but circulate in the community.

Aims Small studies and observations suggested that exercise training may improve peak oxygen consumption (peakVO(2)) in patients with advanced heart failure and left ventricular assist device (LVAD). We investigated whether in this patient group a supervised exercise training can improve exercise capacity.Methods and results In this multicentre, prospective, randomized, controlled trial, patients with stable heart failure and LVAD were randomly assigned (2:1) to 12 weeks of supervised exercise training or usual care, with 12 weeks of follow-up. The primary endpoint was the change in peakVO(2) after 12 weeks (51 patients provided a power of 90% with an expected group difference in peakVO(2) of 3 ml/kg/min). Secondary endpoints included changes in submaximal exercise capacity and quality of life. Among 64 patients enrolled (97% male, mean age 56 years), 54 were included in the analysis. Mean difference in the change of peakVO(2) after 12 weeks was 0.826 ml/min/kg (95% confidence interval [CI] -0.37, 2.03; p = 0.183). There was a positive effect of exercise training on 6-min walk distance with a mean increase in the intervention group by 43.4 m (95% CI 16.9, 69.9; p = 0.0024), and on the Kansas City Cardiomyopathy Questionnaire physical domain score (mean 14.3, 95% CI 3.7, 24.9; p = 0.0124), both after 12 weeks. The overall adherence was high (71%), and there were no differences in adverse events between groups.Conclusion In patients with advanced heart failure and LVAD, 12 weeks of exercise training did not improve peakVO(2) but demonstrated positive effects on submaximal exercise capacity and physical quality of life.

Background Driveline infections (DLI) are a serious complication in patients with left ventricular assist devices (LVAD). Apart from the differentiation between superficial and deep DLI, there is no consensus on the classification of the severity of DLI. Little is known about risk factors and typical bacteria causing DLI in centrifugal-flow LVADs.Methods In this single-center study with 245 patients, DLI were classified by their local appearance using a modification of a score suggested by the Sharp Memorial group. The driveline exit site was inspected routinely every 6 months.Results Severe DLI were detected in 34 patients (15%) after 6 months and in 24 patients (22%) after 24 months. The proportion of patients with DLI increased significantly during the follow-up (p = 0.0096). The most common bacteria in local smears were Corynebacterium, coagulase-negative Staphylococcus, and Staphylococcus aureus. Fifty-nine patients were hospitalized more than once for DLI. In these patients, S. aureus was the most common bacterium. It was also the most common bacterium in blood cultures. Higher BMI, no partnership, and a HeartMate 3 device were identified as risk factors for DLI in a multivariable cause-specific Cox regression.ConclusionThis study is a standardized analysis of DLI in a large cohort with centrifugal-flow LVADs. In this single-center study with 245 patients with left ventricular assist devices, driveline infections (DLI) were classified by their local appearance using a modification of a score suggested by the Sharp Memorial group. The proportion of patients with DLI increased significantly during the follow-up (p = 0.0096). Higher BMI, no partnership, and a HeartMate 3 device were identified as risk factors for DLI in a multivariable cause-specific Cox regression. Conclusion This study is a standardized analysis of DLI in a large cohort with centrifugal-flow LVADs.

Background: Chronic inducible urticaria (CIndU) is a subtype of chronic urticaria (CU) which require specific physical or non-physical triggers to occur. They may be isolated or may coexist with chronic spontaneous urticaria (CSU). Despite their frequent appearance in dermatology clinics, there is scarce information on the distinguishing features among the most common subtypes of CIndU as well as isolated CIndU versus CSU plus CIndU. Objectives: To compare clinical and laboratory characteristics, and comorbid conditions among the most common CIndU types and isolated CIndU versus CSU plus CIndU. Methods: We retrospectively analysed CIndU patients and compared patients' demographic, clinical and laboratory characteristics across isolated CIndU, CSU plus CIndU, symptomatic dermographism (SD), cold urticaria (ColdU) and cholinergic urticaria (ChoU). Results: A total of 423 patients (similar to 70% isolated CIndU, similar to 30% CSU plus CIndU, similar to 5% mixed CIndU subtypes) were included in the study. The most frequent CIndU subtypes were SD (68.6%; 290/423), ColdU (11.4%; 48/423) and ChoU (10.9%; 46/423). Isolated CIndU patients were younger than CSU plus CIndU (33.74 +/- 12.72 vs. 37.06 +/- 11.84, p = 0.010). Angioedema, emergency referrals, need for systemic steroids, comorbid systemic disorders were more frequent and baseline urticaria control test scores were lower in CSU plus CIndU patients (vs. CIndU, p < 0.001, p = 0.008, p < 0.001, p = 0.031, p = 0.036, respectively). Among CIndU subtypes, ChoU patients were younger (24.9 +/- 12.2 vs. 34.47 +/- 12.12 vs. 31.38 +/- 14.95; p < 0.001) and had male predominance (p < 0.001) while SD patients had no angioedema (p < 0.001) and had higher frequency of increased total IgE levels (p = 0.006). Conclusions: Isolated CIndU and CSU plus CIndU seems to be different endotypes of CU where CSU plus CIndU presents a more severe and refractory course. There are distinctive features of each CIndU subtype. These suggest involvement of different pathomechanistic pathways in these subtypes that need to be clarified in future studies.

Background Primary care physicians (PCP) play a key role in the care of people living with dementia. However, the implementation and practicability of the German S3 Dementia Guideline in primary care remain unclear. The main objective of the present study was to evaluate an intervention for improving guideline-based dementia care in primary care.DesignA two-arm, 9-month follow-up cluster-randomized controlled trial with two parallel groups.Setting28 primary care practices in Berlin and the surrounding area in Germany.ParticipantsA total of N = 28 PCP, N = 91 people living with dementia, and N = 88 informal caregivers participated in the trial.InterventionA tablet-based intervention to improve adherence to the German S3 Dementia Guideline in primary care was compared to a control group (care as usual plus a handbook on dementia). MeasurementsAdherence to dementia guideline (primary outcome) was measured on PCP' (23 items) and informal caregivers' level (19 items) with a self-developed checklist. Secondary outcomes (quality of life, neuropsychiatric symptoms, activities of daily living, general health status, depression, and caregiver burden) were measured with standardized assessments. Also, post-hoc per-protocol analyses were conducted.ResultsNo differences in guideline adherence between the intervention and the control group were observed. Further, no significant impact of the intervention on secondary outcomes was detected.ConclusionThe DemTab Study did not improve self-reported guideline adherence in PCP. However, important implementation barriers such as lack of interoperability and low applicability of existing German S3 Dementia Guideline in the primary care setting were identified and are being discussed.Trial registration: The DemTab trial was prospectively registered with the ISRCTN registry (Trial registration number: ISRCTN15854413). Registered 01 April 2019, .ConclusionThe DemTab Study did not improve self-reported guideline adherence in PCP. However, important implementation barriers such as lack of interoperability and low applicability of existing German S3 Dementia Guideline in the primary care setting were identified and are being discussed.Trial registration: The DemTab trial was prospectively registered with the ISRCTN registry (Trial registration number: ISRCTN15854413).

Objective: Family-based treatment (FBT) for youth with anorexia nervosa (AN), has not been compared to inpatient, multimodal treatment (IMT). Method: Prospective, non-randomized pilot feasibility study of adolescents with AN receiving FBT (n = 31), and as a reference point for exploratory outcome comparisons IMT (n = 31), matched for baseline age and percent median BMI (%mBMI). Feasibility of FBT in youth fulfilling criteria for IMT was assessed via study recruitment and retention rates; acceptability via drop-out and caregiver strain; safety via adverse events; preliminary treatment effectiveness between groups was assessed via a change in %mBMI, AN psychopathology (Eating Disorder Examination-Questionnaire, EDE-Q), and hospital days, over 12 months with intent-to-treat, mixed models repeated measures analyses covering post-intervention usual care until 12 months.<br Results: Taking into account that 8 FBT patients (25.8%) crossed over to IMT due to lack of weight gain or psychiatric concerns, FBT and IMT were similarly feasible, acceptable, and safe, apart from more physical antagonism toward others in FBT (p = .010). FBT lasted longer (median [interquartile range, IQR]; 33.6 [17.4, 49.9] vs. 17.3 [14.4, 24] weeks, p < .001), but required fewer hospital days than IMT (median, [IQR], FBT = 1 [0, 16] vs. IMT = 123 [101, 180], p < .001). Baseline comorbidity-adjusted changes over 12 months did not differ between groups in %mBMI (FBT = 12.6 +/- 11.9 vs. IMT = 13.7 +/- 9.1; p = .702) and EDE-Q global score (median, [IQR]; FBT = -1.2 [-2.3, 0.2] vs. IMT = -1.3 [-2.8, -0.4]; p = .733). Discussion: Implementing FBT in this pilot study was feasible, acceptable, and safe for youth eligible for IMT according to German S3 guidelines. Non-inferiority of FBT versus IMT requires confirmation in a sufficiently large multicenter RCT. Public Significance: This pilot study with 62 adolescent patients with anorexia ner vosa demonstrated that for 2/3rd of patients eligible for a long hospitalization in the German health care system, outpatient, Family-based treatment (FBT) was a safe and feasible treatment alternative. Over 12 months, FBT lead to similar weight gain and reduction in eating disorder cognitions as inpatient treatment with fewer hospital days. This pilot study needs to be followed up by a larger, multicenter trial.

Despite molecular selection, patients (pts) with RAS wildtype mCRC represent a heterogeneous population including diversity in metastatic spread. We investigated metastatic patterns for their prognostic and predictive impact on maintenance therapy with 5-fluorouracil/folinic acid +/- panitumumab. The study population was stratified according to (1) number of involved metastatic sites (single vs multiple organ metastasis), liver-limited disease vs (2) liver metastasis plus one additional site, and (3) vs liver metastasis plus >= two additional sites. Kaplan-Meier method and Cox regressions were used to correlate efficacy endpoints. Single organ metastasis was observed in 133 pts (53.6%) with 102 pts (41.1%) presenting with liver-limited disease, while multiple organ metastases were reported in 114 pts (46.0). Multiple compared to single organ metastases were associated with less favorable PFS (HR 1.48, 95% CI 1.13-1.93; P = .004) and OS (HR 1.37, 95% CI 0.98-1.93; P = .068) of maintenance therapy. While metastatic spread involving one additional extrahepatic site was not associated with clearly impaired survival compared to liver-limited disease, pts with liver metastasis plus >= two additional sites demonstrated less favorable PFS (HR 1.92, 95% CI 1.30-2.83; P < .001), and OS (HR 2.38, 95% CI 1.51-3.76; P < .001) of maintenance therapy. Pmab-containing maintenance therapy appeared active in both pts with multiple (HR 0.58; 95% CI, 0.39-0.86; P = .006) as well as to a lesser numerical extent in pts with single organ metastasis (HR 0.83; 95% CI, 0.57-1.21; P = .332; Interaction P = .183). These data may support clinical decisions when EGFR-based maintenance therapy is considered.

Purpose: In analyzing pregnancy data concerning drug exposure in the first trimester, the risk of spontaneous abortions is of primary interest. For estimating the cumulative incidence function, the Aalen-Johansen estimator is typically used, and competing risks such as induced abortion and livebirth are considered. However, the delayed study entry can lead to overly small risk sets for the first events. This results in large jumps in the estimated cumulative incidence function of spontaneous abortions or induced abortions using the Aalen-Johansen estimator, and consequently in an overestimation of the probability.Methods: Several approaches account for early overly small risk sets. The first approach is conditioning on the event time being greater than the event time causing the large jump. Second, the events can be ignored by censoring them. Third, the events can be postponed until a large enough number is at risk. These three approaches are compared.Results: All approaches are applied using data of 54 lacosamide-exposed pregnancies. The Aalen-Johansen estimate of the probability of spontaneous abortion is 22.64%, which is relatively large for only three spontaneous abortions in the dataset. The conditional approach and the ignore approach have an estimated probability of 7.17%. In contrast, the estimate of the postpone approach is 16.45%. In this small sample, bootstrapped confidence intervals seem more accurate.Conclusions: In the analyses of pregnancy data with rare events, the postpone approach is favorable as no events are excluded. However, the approach that ignores early events has the narrowest confidence interval.

Background: Omalizumab, an anti-IgE monoclonal antibody, is an effective treatment in chronic spontaneous urticaria (CSU). Predictors of fast and good response for omalizumab treatment have not yet been identified and characterized.Objective: To evaluate whether soluble FceRI (sFceRI), a marker of IgE-mediated mast cell activation, predicts the time of response to omalizumab in CSU.Methods: Sera of 67 CSU patients were obtained before omalizumab treatment and analysed for sFceRI levels by ELISA (2 ng/mL was used as cut-off for elevated sFceRI). Treatment response during the first 4 weeks was assessed with the urticaria activity score (UAS7), urticaria control test (UCT) and the rolling UAS7 (rUAS7).Results: Elevated pre-treatment sFceRI levels were detected in more than 70% of patients with completely controlled disease (UCT = 16) and well-controlled disease (UCT = 12-15) and were significantly associated with disease control (?(2) = 4.94, p < 0.05). More than half of the patients (14/25) with low levels had poor disease control (UCT < 12). Of the patients who achieved complete and marked UAS7 response, respectively, 75% and 63% had elevated baseline sFceRI levels. Post-treatment UAS7 scores were lower in patients with elevated sFceRI levels reaching statistical significance at Week 3 (p < 0.05). Patients with elevated baseline sFceRI levels achieved rUAS7 = 6 and = 0 earlier than those with lower levels (Days 9 vs. 13 and Days 12 vs. 14, respectively).Conclusion: Elevated sFceRI serum levels predict early and good response to treatment with omalizumab, which may help to better design treatment options for CSU patients.

Purpose: Depicting the stiffness of biological soft tissues, MR elastography (MRE) has a wide range of diagnostic applications. The purpose of this study was to improve the temporal resolution of 2D hepatic MRE in order to provide more rapid feedback on the quality of the wavefield and ensure better temporal sampling of respiration-induced stiffness changes.Methods: We developed a rapid MRE sequence that uses 2D segmented gradient-echo spiral readout to encode 40 Hz harmonic vibrations and generate stiffness maps within 625 ms. We demonstrate the use of this technique as a rapid test for shear wave amplitudes and overall MRE image quality and as a method for monitoring respiration-induced stiffness changes in the liver in comparison to 3D MRE and ultrasound-based time-harmonic elastography.Results: Subsecond MRE allowed monitoring of increasing shear wave amplitudes in the liver with increasing levels of external stimulation within a single breath-hold. Furthermore, the technique detected respiration-induced changes in liver stiffness with peak values (1.83 +/- 0.22 m/s) at end-inspiration, followed by softer values during forced abdominal pressure (1.60 +/- 0.22 m/s) and end-expiration (1.49 +/- 0.22 m/s). The effects of inspiration and expiration were confirmed by time-harmonic elastography.Conclusion: Our results suggest that subsecond MRE of the liver is useful for checking MRE driver settings and monitoring breathing-induced changes in liver stiffness in near real time.

Background and purpose: Although chronic inflammatory demyelinating polyneuropathy (CIDP) is understood as a disease affecting the peripheral nervous system, mild cognitive dysfunction, particularly in the executive domain, has been described to form part of the condition. Here our interest lay in CIDP-related theory of mind (ToM) capacities as an aspect of social cognition relevant for many aspects of everyday life.Methods: Twenty-nine patients with CIDP and 23 healthy controls participated in this study. They were subjected to overview cognitive testing, different executive function (EF) tasks, as well as to the Faux Pas Recognition Task (FPRT) for assessing cognitive ToM and the Reading the Mind in the Eyes Test (RMET) with respect to affective ToM.Results: Persons with CIDP and controls did not differ with respect to their overall cognitive state. However, in the German verbal fluency standard, the digit span forward and the digit span backward tests used as EF tasks patients performed significantly worse than controls. Further, performance was abnormally low in the FPRT, whilst the groups did not differ with respect to RMET results. The FPRT and digit span backward results correlated with each other.Conclusions: Patients with CIDP showed deficits in cognitive ToM performance together with EF dysfunction, whilst affective ToM was preserved. Altogether, the results suggest that low cognitive ToM capacities in patients with CIDP arise as a particular aspect of disease-related executive dysfunction.

The study objective was to estimate the efficacy and safety of chlormethiazole in older adults experiencing insomnia (sleep disorder). We therefore systematically searched Medline, Scopus, the Cochrane Library, PsycINFO, Ovid, ZB MED and PMC through December 2021 for randomized-controlled trials including patients > 60 years old with insomnia treated with chlormethiazole. Standardized mean differences or odds ratios with 95% confidence intervals were calculated for the main outcome parameters: sleep duration, onset of sleep, quality of sleep, adverse events or drop-out rates compared with placebo and other drugs. Risk of bias was assessed using the Cochrane tool. Eight randomized-controlled trials with 424 patients were included. Chlormethiazole significantly increased the duration of sleep when compared with placebo (standardized mean difference = 0.61; 95% confidence interval = 0.11-1.11; p = 0.02). More patients receiving chlormethiazole had adequate quality of sleep than those receiving other drugs (odds ratio = 1.44; 95% confidence interval = 1.04-1.98; p = 0.03). No differences were found regarding the onset of sleep (standardized mean difference = 1.07; 95% confidence interval = 0.79-1.46; p = 0.65). Drop-out rates were significantly lower under chlormethiazole treatment when compared with other drugs (odds ratio = 0.51; 95% confidence interval = 0.26-0.99; p = 0.05) and did not differ from placebo treatment (odds ratio = 1.37; 95% confidence interval = 0.23-8.21; p = 0.73). Side-effects such as "hangover" and daytime drowsiness occurred less frequently during chlormethiazole treatment compared with other drugs in three out of four studies, but differences were not significant (odds ratio = 0.24; 95% confidence interval = 0.04-1.48; p = 0.12). In conclusion, chlormethiazole showed significant effects on the duration and the quality of sleep with better tolerability if compared with other drugs in older adults with insomnia.

Background Deep brain stimulation (DBS) is an effective treatment option for patients with Parkinson's disease (PD). However, clinical programming remains challenging with segmented electrodes.Objective Using novel sensing-enabled neurostimulators, we investigated local field potentials (LFPs) and their modulation by DBS to assess whether electrophysiological biomarkers may facilitate clinical programming in chronically implanted patients.Methods Sixteen patients (31 hemispheres) with PD implanted with segmented electrodes in the subthalamic nucleus and a sensing-enabled neurostimulator were included in this study. Recordings were conducted 3 months after DBS surgery following overnight withdrawal of dopaminergic medication. LFPs were acquired while stimulation was turned OFF and during a monopolar review of both directional and ring contacts. Directional beta power and stimulation-induced beta power suppression were computed. Motor performance, as assessed by a pronation-supination task, clinical programming and electrode placement were correlated to directional beta power and stimulation-induced beta power suppression.Results Better motor performance was associated with stronger beta power suppression at higher stimulation amplitudes. Across directional contacts, differences in directional beta power and the extent of stimulation-induced beta power suppression predicted motor performance. However, within individual hemispheres, beta power suppression was superior to directional beta power in selecting the contact with the best motor performance. Contacts clinically activated for chronic stimulation were associated with stronger beta power suppression than non-activated contacts.Conclusions Our results suggest that stimulation-induced beta power suppression is superior to directional beta power in selecting the clinically most effective contact. In sum, electrophysiological biomarkers may guide programming of directional DBS systems in PD patients.

Germline pathogenic variants in isocitrate dehydrogenase 1 (IDH1) can lead to a rare neurodevelopmental disorder called metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria, including severe skeletal and cerebral anomalies. To the best of our knowledge, no prenatal case of an IDH1 pathogenic variant has been reported in literature. Somatic sequence variants in IDH1/2 genes are described in distinct cancers, premalignant diseases and rare inherited metabolic disorders. Amniocentesis and further genetic testing including trio exome sequencing were performed due to suspicious findings on a second trimester routine prenatal ultrasound examination. The fetus was found to have growth restriction, cerebral abnormalities (ex vacuo hydrocephalus, cerebellar and vermian hypoplasia, corpus callosum dysgenesis), brachycephaly, narrow chest, persistent left superior vena cava, liver calcifications, hyperechogenic bowel, short tubular bones and joint contractures. A de novo heterozygous variant in the IDH1 gene was detected via trio exome sequencing. The prenatal diagnosis of a de novo pathogenic variant in IDH1 in a fetus with the described phenotype, obtained through trio exome sequencing, helped parents and providers with an informed decision making about pregnancy management. What is already known about this topic? Mutations in the isocitrate dehydrogenase (IDH1) gene are associated with cancers, including glioma and acute myeloid leukemia, premalignant diseases, as well as with rare inborn errors of metabolism.There is currently very little information about the fetal phenotype associated with IDH1 pathogenic variants.What does this study add?We report prenatal findings in the central nervous system, skeletal, hepatic and cardiovascular systems associated with germline pathogenic variants in IDH1.This information can help parents and healthcare providers with an informed decision making regarding affected pregnancies.