Association of multiple sclerosis and sudden sensorineural hearing loss

Peer reviewe

Deriving modified rankin scores from medical records

<p><b>Background and Purpose:</b> Modified Rankin score (mRS) is traditionally graded using a face-to-face or telephone interview. Certain stroke assessment scales can be derived from a review of a patient’s case-record alone. We hypothesized that mRS could be successfully derived from the narrative within patient case-records.</p> <p><b>Methods:</b> Sequential patients attending our cerebrovascular outpatient clinic were included. Two independent, blinded clinicians, trained in mRS, assessed case-records to derive mRS. They scored “certainty” of their grading on a 5-point Likert scale. Agreement between derived and traditional face-to-face mRS was calculated using attribute agreement analysis.</p> <p><b>Results:</b> Fifty patients with a range of disabilities were included. Case-record appraisers were poor at deriving mRS (k=0.34 against standard). Derived mRS grades showed poor agreement between observers (k=0.33). There was no relationship between certainty of derived mRS and proportion of correct grades (P=0.727).</p> <p><b>Conclusion:</b> Accurate mRS cannot be derived from standard hospital records. Direct mRS interview is still required for clinical trials.</p&gt

Stroke outcome in clinical trial patients deriving from different countries

<p><b>Background and Purpose:</b> Stroke incidence and outcome vary widely within and across geographical locations. We examined whether differences in index stroke severity, stroke risk factors, mortality, and stroke outcome across geographical locations remain after adjusting for case mix.</p> <p><b>Methods:</b> We analyzed 3284 patients from the Virtual International Stroke Trials Archive (VISTA). We used logistic regression to examine the incidence of mild index stroke, functional, and neurological outcomes after accounting for age, medical history, year of trial recruitment, and initial stroke severity in the functional and neurological outcome analyses. We examined mortality between geographical regions using a Cox proportional hazards model, accounting for age, initial stroke severity, medical history, and year of trial recruitment.</p> <p><b>Results</b> Patients enrolled in the USA and Canada had the most severe index strokes. Those recruited in Austria and Switzerland had the best functional and neurological outcomes at 90 days (P<0.05), whereas those enrolled in Germany had the worst functional outcome at 90 days (P=0.013). Patients enrolled in Austria, Switzerland, Belgium, Netherlands, Finland, Germany, Greece, Israel, Spain, and Portugal had a significantly better survival rate when compared with those enrolled in USA and Canada. Patients enrolled in trials after 1998 had more severe index strokes, with no significant difference in outcome compared with those enrolled before 1998.</p> <p><b>Conclusion:</b> We identified regional variations in index stroke severity, outcome, and mortality for patients enrolled in ischemic stroke clinical trials over the past 13 years that were not fully explained by case mix. Index stroke severity was greater in patients enrolled after 1998, with no significant improvement in outcomes compared to those enrolled before 1998.</p&gt

Expression of CXCL10 is associated with response to radiotherapy and overall survival in squamous cell carcinoma of the tongue

Five-year survival for patients with oral cancer has been disappointingly stable during the last decades, creating a demand for new biomarkers and treatment targets. Lately, much focus has been set on immunomodulation as a possible treatment or an adjuvant increasing sensitivity to conventional treatments. The objective of this study was to evaluate the prognostic importance of response to radiotherapy in tongue carcinoma patients as well as the expression of the CXC-chemokines in correlation to radiation response in the same group of tumours. Thirty-eight patients with tongue carcinoma that had received radiotherapy followed by surgery were included. The prognostic impact of pathological response to radiotherapy, N-status, T-stage, age and gender was evaluated using Cox's regression models, Kaplan-Meier survival curves and chi-square test. The expression of 23 CXC-chemokine ligands and their receptors were evaluated in all patients using microarray and qPCR and correlated with response to treatment using logistic regression. Pathological response to radiotherapy was independently associated to overall survival with a 2-year survival probability of 81 % for patients showing a complete pathological response, while patients with a non-complete response only had a probability of 42 % to survive for 2 years (p = 0.016). The expression of one CXC-chemokine, CXCL10, was significantly associated with response to radiotherapy and the group of patients with the highest CXCL10 expression responded, especially poorly (p = 0.01). CXCL10 is a potential marker for response to radiotherapy and overall survival in patients with squamous cell carcinoma of the tongue

Initial treatment strategy and clinical outcomes in Finnish MS patients : a propensity-matched study

Background The optimal treatment strategy with disease-modifying therapies (DMTs) in relapsing-remitting multiple sclerosis (RRMS) remains uncertain. Objective To compare outcomes of initial treatment with infusion therapies and starting therapy with medium efficacy therapy in a propensity-matched cohort of Finnish RRMS patients. Methods A total of 154 RRMS patients initiating natalizumab, alemtuzumab, ocrelizumab or rituximab as first DMT (high efficacy DMT, heDMT group) and 1771 patients initially treated with injectable therapies, teriflunomide or dimethylfumarate and escalated based on disease activity (moderate efficacy DMT, meDMT group) were identified from the Finnish MS registry. Nearest neighbor propensity matching (1:1, caliper 0.1) was performed for age, sex, baseline Expanded Disability Status Scale (EDSS), annual relapse rate (ARR) one year prior DMT and time since MS symptom onset. Primary outcome was time to 6-month confirmed EDSS progression and the secondary outcome time to first relapse. Results In the propensity-matched group comparisons, the probability of 6-month confirmed disability progression (CDP) at 5 years after DMT start was 28.4% (95% CI 15.7-39.3) in the heDMT group (n = 66) and 47.0% (95% CI 33.1-58.1) in meDMT group (n = 66), p = 0.013. Probability of relapse at 5 years was 34.6% (95% CI 24.1-43.6) for heDMT (n = 105) and 47.2% (95% CI 36.6-56.1) for meDMT (n = 105), p = 0.019. Conclusions Initiating MS-therapy with heDMT significantly reduced the risk of 5-year disability progression and relapse compared to using meDMT as first DMT choice in propensity-matched groups of Finnish MS-patients.Peer reviewe

Common origin of the gelsolin gene variant in 62 Finnish AGel amyloidosis families

Finnish gelsolin amyloidosis (AGel amyloidosis) is an autosomal dominantly inherited systemic disorder with ophthalmologic, neurologic and dermatologic symptoms. Only the gelsolin (GSN) c.640G>A variant has been found in the Finnish patients thus far. The purpose of this study was to examine whether the Finnish patients have a common ancestor or whether multiple mutation events have occurred at c.640G, which is a known mutational hot spot. A total of 79 Finnish AGel amyloidosis families including 707 patients were first discovered by means of patient interviews, genealogic studies and civil and parish registers. From each family 1-2 index patients were chosen. Blood samples were available from 71 index patients representing 64 families. After quality control, SNP array genotype data were available from 68 patients from 62 nuclear families. All the index patients had the same c.640G>A variant (rs121909715). Genotyping was performed using the Illumina CoreExome SNP array. The homozygosity haplotype method was used to analyse shared haplotypes. Haplotype analysis identified a shared haplotype, common to all studied patients. This shared haplotype included 17 markers and was 361 kb in length (GRCh37 coordinates 9:124003326–124364349) and this level of haplotype sharing was found to occur highly unlikely by chance. This GSN haplotype ranked as the largest shared haplotype in the 68 patients in a genome-wide analysis of haplotype block lengths. These results provide strong evidence that although there is a known mutational hot spot at GSN c.640G, all of the studied 62 Finnish AGel amyloidosis families are genetically linked to a common ancestor.Peer reviewe

Complications in lymph node excision in the head and neck area

Background Although needle biopsy is widely used in work-up of lymphadenopathy, lymph node excision (LNE) is often required especially in lymphoma diagnostics. LNE is an invasive procedure, which carries a potential risk of complications. However, comprehensive studies evaluating the spectrum and occurrence of complications are lacking. Aims/Objectives This study addresses the role of preoperative needle biopsies in patients who underwent LNE. Furthermore, surgical complications related to LNE are analyzed. Materials and methods Altogether 321 patients, who underwent LNE in two-year period in 2018-19, and fulfilled our study criteria, were included. Patients' data were retrieved from the electronic patient records. Results The surgical complication rate was 5.9%. Most of the complications (n = 16; 84.2%) were categorized as minor (I-II) according to the Clavien-Dindo scale. The remaining three (15.8%), all hemorrhages, were categorized as major complications and required intervention. Preoperative needle biopsy might have avoided the need for LNE in some patients, which we discuss in this study. Conclusions and significance Surgical complications after LNE in the head and neck area are rare and mostly minor. Needle biopsy is often recommended preoperatively to avoid unnecessary operations and to refrain performing LNE for patients with non-lymphatic malignancy.Peer reviewe

Initial treatment strategy and clinical outcomes in Finnish MS patients: a propensity-matched study

BackgroundThe optimal treatment strategy with disease-modifying therapies (DMTs) in relapsing–remitting multiple sclerosis (RRMS) remains uncertain.ObjectiveTo compare outcomes of initial treatment with infusion therapies and starting therapy with medium efficacy therapy in a propensity-matched cohort of Finnish RRMS patients.MethodsA total of 154 RRMS patients initiating natalizumab, alemtuzumab, ocrelizumab or rituximab as first DMT (high efficacy DMT, heDMT group) and 1771 patients initially treated with injectable therapies, teriflunomide or dimethylfumarate and escalated based on disease activity (moderate efficacy DMT, meDMT group) were identified from the Finnish MS registry. Nearest neighbor propensity matching (1:1, caliper 0.1) was performed for age, sex, baseline Expanded Disability Status Scale (EDSS), annual relapse rate (ARR) one year prior DMT and time since MS symptom onset. Primary outcome was time to 6-month confirmed EDSS progression and the secondary outcome time to first relapse.ResultsIn the propensity-matched group comparisons, the probability of 6-month confirmed disability progression (CDP) at 5 years after DMT start was 28.4% (95% CI 15.7–39.3) in the heDMT group (n = 66) and 47.0% (95% CI 33.1–58.1) in meDMT group (n = 66), p = 0.013. Probability of relapse at 5 years was 34.6% (95% CI 24.1–43.6) for heDMT (n = 105) and 47.2% (95% CI 36.6–56.1) for meDMT (n = 105), p = 0.019.ConclusionsInitiating MS-therapy with heDMT significantly reduced the risk of 5-year disability progression and relapse compared to using meDMT as first DMT choice in propensity-matched groups of Finnish MS-patients.</p

A Rigid Multiple Resonance Thermally Activated Delayed Fluorescence Core Toward Stable Electroluminescence and Lasing

The investigation of organic light-emitting diodes (OLEDs) and organic laser devices with thermally activated delayed fluorescence (TADF) molecules is emerging due to the potential of harnessing triplets. In this work, a boron/nitrogen multiple-resonance TADF polycyclic framework fusing carbazole units (CzBNPh) was proposed. CzBNPh exhibited a narrowband emission (<30 nm), a unity photoluminescence quantum yield, and a fast radiative rate. Consequently, CzBNPh demonstrated a low distributed feedback (DFB) lasing threshold of 0.68 μJ cm−2. Furthermore, the stimulated emission zone of CzBNPh was effectively separated from its singlet and triplet absorption, thereby minimizing the singlet-triplet annihilation under long-pulsed excitation ranging from 20 μs to 2.5 ms. Significantly, the enhanced rigid molecular conformation, thermal stability, and photo-stability resulted in improved lasing and electroluminescence stability compared to that of 5,9-diphenyl-5,9-diaza-13b-boranaphtho[3,2,1-de]anthracene (DABNA)-core. These findings indicate the potential of CzBN-core as a promising framework for achieving long-pulsed wave and electrically-pumped lasing in the future.journal articl

Humoral response to John Cunningham virus during pregnancy in multiple sclerosis

ConclusionsJCV-Ab levels remain unaltered during MS pregnancy, while the total IgG concentration is reduced/diluted due to increasing plasma volumes during the course of pregnancy. This may imply a biologically significant alteration in the immune response to JCV during MS pregnancy.</p