Medically Unexplained Oropharyngeal Dysphagia at the University Hospital ENT Outpatient Clinic for Dysphagia: A Cross-Sectional Cohort Study

Medically unexplained oropharyngeal dysphagia (MUNOD) is a rare condition. It presents without demonstrable abnormalities in the anatomy of the upper aero-digestive tract and/or swallowing physiology. This study investigates whether MUNOD is related to affective or other psychiatric conditions. The study included patients with dysphagic complaints who had no detectible structural or physiological abnormalities upon swallowing examination. Patients with any underlying disease or disorder that could explain the oropharyngeal dysphagia were excluded. All patients underwent a standardized examination protocol, with FEES examination, the Hospital Anxiety and Depression Scale (HADS), and the Dysphagia Severity Scale (DSS). Two blinded judges scored five different FEES variables. None of the 14 patients included in this study showed any structural or physiological abnormalities during FEES examination. However, the majority did show abnormal piecemeal deglutition, which could be a symptom of MUNOD. Six patients (42.8%) had clinically relevant symptoms of anxiety and/or depression. The DSS scores did not differ significantly between patients with and without affective symptoms. Affective symptoms are common in patients with MUNOD, and their psychiatric conditions could possibly be related to their swallowing problems

Predictors of gallstone composition in 1025 symptomatic gallstones from Northern Germany

BACKGROUND: Gallstones represent a prevalent and costly health problem. The changing epidemiology and the emerging non-surgical interventions for gallstone disease necessitate the definition of target populations for future therapies. This study aimed to define patterns of gallstone composition and identify demographic predictors of gallstone composition in a large sample of symptomatic gallstones from Northern Germany. METHODS: One thousand and seventy-four post-cholecystectomy gallstone specimens were obtained. Demographic and clinical information was provided by questionnaire (N = 1025 independent individuals with complete information). Two samples from each gallstone were analyzed using Fourier transformed infrared spectrometry. RESULTS: The most prevalent substance was cholesterol, which was detected in 95.0% of gallstone specimens. Bilirubin and bilirubinate were present in 30.0% and calcium was detected in 10.0% of the spectra. Ninety-two percent of measurements from the same stone yielded the same "main" substances, indicating a homogenous stone composition in most cases. Female sex and higher body mass index (BMI) were associated with the presence of cholesterol as a main substance in the gallstones (p < 0.001). CONCLUSION: The changing epidemiology of gallstone disease is reflected by a marked shift in stone composition: Only two percent of stones in this study were pigment stones as compared to 91% percent of stones containing cholesterol as a main substance. Obese individuals from Germany with a BMI > 30 kg/m(2 )have in 95% cholesterol-dominant gallstones and represent a potential target population for non-surgical interventions for the prevention or treatment of cholesterol stones

Whole genome sequencing for USH2A-associated disease reveals several pathogenic deep-intronic variants that are amenable to splice correction

A significant number of individuals with a rare disorder such as Usher syndrome (USH) and (non-)syndromic autosomal recessive retinitis pigmentosa (arRP) remain genetically unexplained. Therefore, we assessed subjects suspected of USH2A-associated disease and no or mono-allelic USH2A variants using whole genome sequencing (WGS) followed by an improved pipeline for variant interpretation to provide a conclusive diagnosis. One hundred subjects were screened using WGS to identify causative variants in USH2A or other USH/arRP-associated genes. In addition to the existing variant interpretation pipeline, a particular focus was put on assessing splice-affecting properties of variants, both in silico and in vitro. Also structural variants were extensively addressed. For variants resulting in pseudoexon inclusion, we designed and evaluated antisense oligonucleotides (AONs) using minigene splice assays and patient-derived photoreceptor precursor cells. Biallelic variants were identified in 49 of 100 subjects, including novel splice-affecting variants and structural variants, in USH2A or arRP/USH-associated genes. Thirteen variants were shown to affect USH2A pre-mRNA splicing, including four deep-intronic USH2A variants resulting in pseudoexon inclusion, which could be corrected upon AON treatment. We have shown that WGS, combined with a thorough variant interpretation pipeline focused on assessing pre-mRNA splicing defects and structural variants, is a powerful method to provide subjects with a rare genetic condition, a (likely) conclusive genetic diagnosis. This is essential for the development of future personalized treatments and for patients to be eligible for such treatments.</p

The relationship between fiberoptic endoscopic evaluation of swallowing outcome and symptoms of anxiety and depression in dysphagic patients

Objectives/HypothesisAffective complaints are involved in bothersome oropharyngeal dysphagia (OD). The aim was to determine the relationship between the severity of OD and affective symptoms. Study DesignProspective cohort study. MethodsOne hundred seven patients underwent a standardized examination protocol including the Hospital Anxiety and Depression Scale and fiberoptic endoscopic evaluation of swallowing (FEES). Two observers independently assessed patient performance on four ordinal FEES-variables (for thin and thick liquid consistency, blindly assessed). The relationship between FEES outcome and the presence of clinically relevant symptoms of anxiety and depression was analyzed using binary logistic regression. ResultsSignificant associations were found between clinically relevant symptoms of anxiety and two variables: piecemeal deglutition (thin liquid consistency only) (P = .026) and postswallow vallecular pooling (thick liquid consistency only) (P = .015). The probability of presenting with anxiety symptoms decreased as the severity of piecemeal deglutition and postswallow vallecular pooling increased. No significant association was found between clinically relevant symptoms of depression and any specific FEES variable. ConclusionsThese data revealed few associations between anxiety symptoms and the measured FEES variables. However, the more severe the score on FEES variables, the less important the affective complaints were. Anxiety seems to play a role in OD, but no causal relationship was found, commensurate with a cross-sectional study design. The contribution of affective symptoms to the development and treatment of OD warrants longitudinal research. Level of Evidence2b Laryngoscope, 126:E199-E207, 201

Swallowing assessment in myotonic dystrophy type 1 using fiberoptic endoscopic evaluation of swallowing (FEES)

This study describes the swallowing function of patients with myotonic dystrophy type 1 (DM1) and the effect of bolus consistency on swallowing in this group. The aim of the study is twofold: (a) to identify which (and to what extent) swallowing variables change for DM1 patients relative to healthy control subjects and (b) to examine whether the degree of oropharyngeal dysphagia is associated with disease severity. Forty-five consecutive DM1 patients and ten healthy subjects underwent a swallowing assessment, at Maastricht University medical Center in the Netherlands. The assessment included a standardized fiberoptic endoscopic evaluation of swallowing (FEES) protocol using different bolus consistencies. Clinical severity of the disease was assessed using the muscular impairment rating scale (MIRS). Significant differences were found between patients and controls for all FEES variables. The magnitude of these differences depended on the bolus consistency. The odds of a more pathological swallowing outcome increased significantly with higher MIRS levels. In conclusion, swallowing function is found to be significantly altered in DM1 patients. The results emphasize the importance of conducting a detailed swallowing assessment in all patients, even those with mild muscle weakness. (C) 2014 Elsevier B.V. All rights reserved

Medically Unexplained Otorhinolaryngological Symptoms: Towards Integrated Psychiatric Care

Objective: To evaluate the presence of medically unexplained otorhinolaryngological symptoms in a patient cohort and propose an interdisciplinary approach for their care. Study Design: Prospective cohort study. Methods: The study describes the population of patients presenting consecutively at the Department of Otorhinolaryngology at the Maastricht University Medical Center. Patients with symptoms who did not meet clear "medical" criteria and were associated with psychological distress and high health care utilization were enrolled in the study by two experienced otorhinolaryngologists following informed consent. The aim of the study is 1) to specify the presence of medically unexplained otorhinolaryngological symptoms and 2) to evaluate the integration of otorhinolaryngological and psychiatric treatment in an interdisciplinary approach in order to help otorhinolaryngologists improve patient care. Results: Of the 102 patients included, 41% (N=42) did not have a proven somatic otorhinolaryngological diagnosis. For only 10.8% (N=4) of the latter, no psychiatric diagnosis had been established. Overall, 78% of the study population (N=80) was diagnosed with psychiatric morbidity/comorbidity, as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Conclusion: The preliminary data suggest that the majority of patients with these unexplained complaints may suffer from under-or undiagnosed psychiatric morbidity. Therefore, easy access to integrated interdisciplinary care (otorhinolaryngology and psychiatry) should be offered to patients with medically unexplained otorhinolaryngological symptoms after detailed information is made available to them about the pathogenesis of the complaints and the foreseen psychosomatic approach

Endovascular thrombectomy in patients with anterior circulation stroke: an emulated real-world comparison

Abstract Background Endovascular thrombectomy (EVT) has been proven effective in anterior circulation stroke due to large vessel occlusion (LVO). However, translation from randomized clinical trials (RCTs) with highly selected patients to real-world requires confirmation, particularly to identify associations outside of strict selection criteria. Aims This study aims to compare functional outcomes after EVT in real-world with those reported in RCTs, and to identify associations with functional outcome after EVT outside RCT-criteria. Methods This study analyzed longitudinal German real-world data from the Stroke Research Consortium in Northern Bavaria (STAMINA) cohort from January, 2015 to June, 2019. We conducted a trial emulation, comparing patients with anterior circulation stroke and LVO meeting selection criteria for RCTs investigating EVT (1) predominantly within 6 hours with those from HERMES meta-analysis, and (2) within 6-24 hours with those from AURORA meta-analysis. We (3) analyzed treatment effects of EVT and association with functional outcome in patients treated outside RCT criteria. Results Of 598 patients, 281 (47.0%) met RCT-criteria for treatment within 6 hours (hereinafter STAMINA-HERMES), 74 (12.4%) met RCT-criteria for treatment within 6–24 hours (STAMINA-AURORA), and 277 (46.3%) patients received EVT outside RCT-criteria. We observed no difference in rates of functional independence or mortality, comparing STAMINA-HERMES with HERMES meta-analysis (mRS 0-1: n=120/281 [43%] vs. 291/633 [46%], p=0.36; mortality: n=34/281 [12%] vs. 97/633 [15%], p=0.20), and STAMINA-AURORA with AURORA meta-analysis (mRS 0-1: n=26/74 [35%] vs. 122/266 [46%], p=0.10, mortality: n=10/74 [14%] vs. 45/266 [17%], p=0.48). Patients treated outside RCT-criteria had worse outcome (mRS 0-1: n=38/277 [14%], mortality: n=90/277 [32%], both p<0.001); possibly driven by pre-existing functional dependence (n=172/277 [62%]). Compared to matched controls, EVT outside of RCT-criteria was associated with lower mortality (absolute treatment effect: -14%, 95% Confidence Interval [CI] -23 to -5, p<0.01), but not with recovery to functional independence or premorbid functional status (treatment effect: 4%, CI -4 to 11, p=0.34), which was associated with lower NIHSS (Odds ratio [OR] 0.86, CI 0.80-0.92, p<0.001) and age (OR 0.95, CI 0.93-0.98, p=0.002). Conclusions Translation of EVT outcomes reported in RCTs into real-world is possible, however, almost half of patients did not meet trial criteria. Identification of patients who functionally benefit from frequently performed EVT outside RCT-criteria requires further investigation. Trial registration Clinicaltrials.gov, NCT04357899