Stable Disease Course Research Articles

Therapy Response and Survival among Patients with Gynecologic Tumors Treated with Transarterial Chemoperfusion and Transarterial Chemoembolization.

Background and Objectives: This study aimed to evaluate the tumor response relating to and survival benefit of transarterial chemoperfusion (TACP) and transarterial chemoembolization (TACE) in the treatment of patients with unresectable gynecologic tumors who are intolerant of or have a suboptimal response to chemotherapy and radiotherapy. Materials and Methods: Between January 2000 and October 2023, 75 patients diagnosed with gynecologic tumors underwent 213 TACP and 154 TACE procedures. Of these, 33 patients were treated with TACP, 20 were treated with TACE, and 22 received a combination of both therapies. A retrospective evaluation of local tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST) was conducted, and survival rates were determined using the Kaplan-Meier estimator. Results: Of the total 75 patients, 50 (67%) maintained a stable course of disease until the completion of therapy, 10 (13%) had a partial response, 2 (3%) had a complete response following thermal ablation, and 13 (17%) experienced progression. Furthermore, a 6% reduction in the sum of the longest diameters and an 8% reduction in tumor volume were observed. The median overall survival was 16.15 months, while the median progression-free survival was 13.19 months. Conclusions: TACP and TACE are potential treatment options for local tumor control in patients with unresectable gynecologic tumors who are intolerant of or show a poor response to chemotherapy and radiotherapy. However, further investigation and adjustment of treatment protocols are required to improve therapy response and survival outcomes.

Natural disease course of chronic visceral acid sphingomyelinase deficiency in adults: A first step toward treatment criteria.

Acid sphingomyelinase deficiency (ASMD) is an ultra-rare lysosomal storage disease with a broad spectrum of manifestations ranging from severe neuropathic forms to attenuated, chronic visceral forms. Manifestations of the chronic visceral subtype are variable and encompass different degrees of hepatosplenomegaly, pulmonary disease and dyslipidemia. The aim of this study was to provide insights into the natural course of adult patients with the chronic visceral subtype. Based on these insights, we proposed tentative criteria for initiation and follow-up of enzyme replacement therapy (ERT). The data of 23 adult patients were collected in a prospective study. Clinical, genetic and demographic data, plasma measurements, abdominal imaging, pulmonary imaging, pulmonary function tests and quality of life questionnaires were collected. Stability of disease based on several clinical, biochemical and radiological markers (i.e., spleen volume, platelet levels, liver volume, alanine aminotransferase [ALT] levels, diffusion capacity of the lungs for carbon monoxide [DLCO] chitotriosidase activity and lysosphingomyelin [LSM]) was assessed. Cardiovascular risk was estimated based on sex, age, smoking, systolic blood pressure and lipid profile. Quality of life was evaluated with the 36-Item Short Form Health Survey and the Health Assessment Questionnaire. Median follow-up was 6.1 years (range 1.3-19.5 years). The most common manifestations were splenomegaly (100%), decreased high-density lipoprotein cholesterol (HDL-C) plasma levels (83%), (signs of) steatosis measured with transient elastography (82%), thrombocytopenia (64%), hepatomegaly (52%) and decreased diffusion capacity (45%). The majority of markers remained stable during follow-up. Twelve patients showed progression of disease: four for spleen volume, two for liver volume, three for DLCO, seven for chitotriosidase activity and three for LSM. One patient showed progression of disease based on four markers, although this patient did not report any problems at the last visit. Cardiovascular risk was estimated and was increased in half of the patients older than 40 years. Patient-reported quality of life did not differ from the general population, but differences in median 36-Item Short Form Health Survey (SF-36) scores of patients with severe pulmonary involvement and those of patients without pulmonary involvement were observed. Tentative criteria for initiation and effect of therapy were proposed. In conclusion, the chronic visceral subtype of ASMD showed a predominantly stable disease course in this cohort. We propose that ERT should be initiated on an individual basis and only in case of progression or symptomatic disease. Collection and analysis of real world data are necessary to refine start, stop and follow-up criteria in the future.

MS treatment de-escalation: review and commentary.

Almost all currently licensed disease-modifying therapies (DMTs) for MS treatment require prolonged if not lifelong administration. Yet, as people age, the immune system has increasingly reduced responsiveness, known as immunosenescence. Many MS DMTs reduce the responsiveness of the immune system, increasing the risks for infections and possibly cancers. As people with MS (pwMS) age, it is recognized that inflammatory MS activity declines. Several studies have addressed de-escalation of DMTs for relapsing MS under special circumstances. Here, we review evidence for de-escalating DMTs as a strategy that is particularly relevant to pwMS of older age. Treatment de-escalation can involve various strategies, such as extended or reduced dosing, switching from high-efficacy DMTs having higher risks to moderately effective DMTs with lesser risks, or treatment discontinuation. Studies have suggested that for natalizumab extended dosing maintained clinical efficacy while reducing the risk of PML. Extended interval dosing of ocrelizumab mitigated the decline of Ig levels. Retrospective and observational discontinuation studies demonstrate that age is an essential modifier of drug efficacy. Discontinuation of MS treatment in older patients has been associated with a stable disease course, while younger patients who discontinued treatment were more likely to experience new clinical activity. A recently completed 2-year randomized-controlled discontinuation study in 260 stable pwMS > 55years found stable clinical multiple sclerosis with only a small increased risk of new MRI activity upon discontinuation. DMT de-escalation or discontinuation in MS patients older than 55years may be non-inferior to continued treatment with immunosuppressive agents having higher health risks. However, despite several small studies, a definite conclusion about treatment de-escalation in older pwMS will require larger and longer studies. Ideally, comparison of de-escalation versus continuation versus discontinuation of DMTs should be done by prospective randomized-controlled trials enrolling sufficient numbers of subjects to allow comparisons for MS patients of both sexes within age groups, such as 55-59, 60-65, 66-69, etc. Optimally, such studies should be 3years or longer and should incorporate testing for specific markers of immunosenescence (such as T-cell receptor excision circles) to account for differential aging of individuals.

Very-long T2-weighted imaging of the non-lesional brain tissue in multiple sclerosis patients.

The purpose of this study is to demonstrate that T2-weighted imaging with very long echo time (TE > 300 ms) can provide relevant information in neurodegenerative/inflammatory disorder. Twenty patients affected by relapsing-remitting multiple sclerosis with stable disease course underwent 1.5T 3D FLAIR, 3D T1-weighted, and a multi-echo sequence with 32 echoes (TE = 10-320 ms). Focal lesions (FL) were identified on FLAIR. T1-images were processed to segment deep gray matter (dGM), white matter (WM), FL sub-volumes with T1 hypo-intensity (T1FL), and dGM volumes (atrophy). Clinical-radiological parameters included Expanded Disability Status Scale (EDSS), disease duration, patient age, T1FL, and dGM atrophy. Correlation analysis was performed between the mean signal intensity (SI) computed on the non-lesional dGM and WM at different TE versus the clinical-radiological parameters. Multivariable linear regressions were fitted to the data to assess the association between the dependent variable EDSS and the independent variables obtained by T1FL lesion load and the mean SI of dGM and WM at the different TE. A clear trend is observed, with a systematic strengthening of the significance of the correlation at longer TE for all the relationships with the clinical-radiological parameters, becoming significant (p < 0.05) for EDSS, T1FL volumes, and dGM atrophy. Multivariable linear regressions show that at shorter TE, the SI of the T2-weighted sequences is not relevant for describing the EDSS variability while the T1FL volumes are relevant, and vice versa, at very-long TEs (around 300 ms); the SI of the T2-weighted sequences significantly (p < 0.05) describes the EDSS variability. By very long TE, the SI primarily originates from water with a T2 longer than 250 ms and/or free water, which may be arising from the perivascular space (PVS). Very-long T2-weighting might detect dilated PVS and represent an unexplored MR approach in neurofluid imaging of neurodegenerative/inflammatory diseases.

Non-syndromic OTX2-associated pattern dystrophy: a 10-year multimodal imaging study

PurposeTo report novel multimodal imaging features and long-term follow-up of Orthodenticle Homeobox 2 (OTX2)-associated pattern Gdystrophy.MethodsA 14-year-old boy referred with glaucoma suspect and macular pigmentation underwent fundus autofluorescence imaging, optical coherence tomography, fluorescein and indocyanine green angiography, visual field test, microperimetry and electrophysiology over a ten-year period. Next-generation sequencing panel identified a de novo heterozygous likely pathogenic OTX2 variant, c.259G>A, [p.(Glu87Lys)].ResultsVisual acuity was 20/40 OD and 20/30 OS. Examination showed bilateral enlarged optic nerve heads and increased disc cupping, multiple cilioretinal arteries, a pigmentary maculopathy with stellate-shaped region of hypoautofluorescence, shallow serous macular detachment, subretinal deposits and temporal avascular retina. Angiography showed no source of leakage and absence of retinal neovascularisation despite extensive peripheral non perfusion. Electrophysiological assessments demonstrated mild progressive rod and cone pathway abnormalities, reduced light-adapted b:a ratio, and reduced Arden ratio on electro-oculogram. Ten-year follow-up confirmed a stable disease course despite persistent submacular fluid. There was no associated pituitary structural abnormality or dysfunction.ConclusionsThis case study contributes to further understanding of OTX2-associated pattern dystrophy, highlighting its stability over 10 years. Further investigation into inter-individual and intrafamilial variability is warranted.

Target area treatment ratio of varied lesions in the cultured pure melanocyte transplantation repigmentation of vitiligo: Aretrospective study.

Autologous cultured pure melanocyte transplantation (CMT) can be utilized to treat stable vitiligo cases, but clinical data are insufficient to improve its efficacy. To evaluate the influence of various factors on the therapeutic effect of CMT, this single-center retrospective study enrolled stable vitiligo patients who underwent CMT between 2009 and2020. Univariate and multivariable analysis were used to determine the factors affecting the outcome of repigmentation. The study included 491 patients with long-term follow-up data (6-120 months). It was found that 69.7% of patients achieved an excellent re-color effect and 18.4% achieved a good re-color effect. There were statistically significant differences in pigmentation between patients with stable disease course, vitiligo type, and lesion site. Overall, a significant positive correlation between the target area treatment ratio of varied lesions and the percentage of repigmentation was found. CMT is effective and well tolerated in the treatment of stable vitiligo. Various factors, especially the target area treatment ratio of varied lesions, should be carefully assessed before using CMT. As the target area treatment ratio of varied lesions could further improve the post-operative repigmentation other than type of vitiligo. This clinic trial was approved by Hangzhou Third People's Hospital (number 2023KA015, national clinical record number MR-33-23-034502).

A single arm Phase I/II trial on the combination of carboplatin, nab-paclitaxel and avastin as first-line treatment for advanced non-squamous non-small cell lung cancer (TORG1424/OLCSG1402: CARNAVAL).

Bevacizumab with platinum doublet therapy including paclitaxel+carboplatin improves the survival of patients with non-squamous non-small cell lung cancer. However, in a previous trial (CA031), paclitaxel+carboplatin led to Grade>3 neutropenia in a Japanese population. Nanoparticle albumin-bound paclitaxel exhibits an improved toxicity profile. We evaluated the safety, dosage and response rate of the nanoparticle albumin-bound paclitaxel+carboplatin + bevacizumab combination in a Japanese population. Chemotherapy-naive patients with advanced non-squamous non-small cell lung cancer were included. The dosage schedule was established in the Phase I trial as follows: 4-6cycles of carboplatin (area under the concentration-time curve=6 on Day 1)+nanoparticle albumin-bound paclitaxel (100mg/m2 on Days 1, 8 and 15)+bevacizumab (15mg/kg on Day 1), followed by maintenance therapy (nanoparticle albumin-bound paclitaxel+bevacizumab). The response rate and presence of adverse effects were evaluated in the Phase II trial. The overall response rate was 56.5% (90% confidence interval: 44.5-68.5), and 93% of patients (43/46) showed tumor shrinkage or maintained a stable disease course. The primary endpoint was achieved. At the median follow-up duration of 42months, the median overall survival was 18.9 (range: 10.5-32.4) months. The most frequently observed Grade≥3 adverse effects were neutropenia (72%), leukopenia (50%) and anemia (30%). All adverse effects were manageable and none resulted in patient death. In conclusion, the nanoparticle albumin-bound paclitaxel + carboplatin + bevacizumab combination is favorable and well tolerated in Japanese patients as first-line treatment for advanced non-squamous non-small cell lung cancer.

The role of genetic factors in pediatric myelodysplastic syndromes with different outcomes

BackgroundPediatric myelodysplastic syndromes (MDS) are rare disorders with an unrevealed pathogenesis. Our aim is to explore the role of genetic factors in the pathogenesis of MDS in children with different outcomes and to discover the correlation between genetic features and clinical outcomes as well as disease characteristics.MethodsWe conducted an analysis of archived genetic data from 26 patients diagnosed with pediatric MDS at our institution between 2015 and 2021, examining the association between different genetic characteristics and clinical manifestations as well as prognosis. Additionally, We presented three cases with distinct genetic background and outcomes as examples to elaborate the role of genetic factors in pediatric MDS with different prognoses.ResultsGenetic variations were detected in 13 out of the 26 patients, including 8 patients with co-occurrence of somatic and germline mutations (CSGMs) and 5 patients with somatic mutations alone. Our analysis revealed that advanced MDS (4/8, 50% vs. 1/5, 20% and 4/11, 36.4%), PD (3/8, 37.5% vs. 1/5, 20% and 1/11 9.1%), and TD (6/8, 75% vs. 2/5, 40% and 2/11, 18.2%) were more common in patients with CSGMs than those with somatic mutations alone or without any mutations. We also found out in our study that 8 patients with CSGMs had evidently different clinical outcomes, and we presented 3 of them as examples for elaboration. Case 1 with germline and somatic mutations of unknown significance had a relatively slow disease course and a good prognosis. Case 2 with compound heterozygous germline SBDS variants and somatic mutations like del20q had a stable disease course and a reversed outcome. Case 3 with a germline GATA2 variant and somatic mutations including − 7 had a rapidly progressive disease course and a worst prognosis.ConclusionOur findings indicate that genetic background of pediatric MDS is closely linked with disease characteristics as well as outcomes and that CSGMs may lead to disease progression. It should be emphasized that the interaction between certain germline variants and somatic mutations, such as SBDS and del20q, may result in hematopoietic stem cell adaptation (improved hematopoiesis) and reversed clinical outcomes, which can facilitate the development of targeted therapy.

Восстановительная терапия больных бронхиальной астмой: в фокусе дыхательная гимнастика с экспираторным сопротивлением

Aim: to evaluate the effectiveness of high-resistance breathing exercises using flutter as a method of rehabilitation therapy for asthma. Patients and Methods: the patients with asthma were divided into two groups. Group 1 (n=40) received breathing exercises as part of their treatment, which consisted of quiet inhalation through the nose and exhalation into the flutter for 3–5 minutes daily, for a total of 14 procedures per course, in addition to their baseline therapy. In group 2 (n=40), patients received similar drug therapy without performing breathing exercises. The control group (n=40) consisted of healthy volunteers who performed breathing exercises as in group 1. We analyzed changes in clinical and functional parameters over time after a single application of the rehabilitation technique, as well as at baseline and after completing treatment (after 14 days). Results: showed a significant increase (p&lt;0.05) in external respiration indices, specifically forced expiratory volume in the 1st second, forced vital capacity (FVC), and expiratory reserve volume in groups 1 and 2. Furthermore, group 1 reported a significant increase (p&lt;0.05) in the time to hold breath, as well as an increase in peak expiratory flow, peak expiratory flow rate (PEFR), and a decrease in the daily variation of PEFR and minute ventilation. After two weeks of treatment, group 1 showed significant improvement. The study showed a decrease in choking incidents, reduced need for bronchodilators, and improvement in symptoms such as cough, dyspnea, expectoration of sputum, its character, and wheezing. Additionally, there was an improvement in disease control and exercise tolerance as demonstrated by the results of the 6-minute walk test. Group 2 showed a stable disease course during the follow-up, but no significant changes in clinical manifestations or pharmacological therapy were reported. In this study, it was found that flutter therapy had a significant and moderate favorable effect on 80% and 20% of patients with asthma, respectively. However, this effect was only maintained in patients who regularly practiced high-resistance breathing exercises. No adverse events were reported. Conclusion: high-resistance breathing exercises can reduce hyperventilation and improve bronchial patency in patients with asthma. Additionally, flutter therapy can decrease the doses of bronchodilators, improve FVC, and positively impact the disease course. KEYWORDS: asthma, breathing exercises, expiratory resistance, flutter therapy. FOR CITATION: Alekseenko S.N., Churyukina E.V., Ukhanova O.P., Kas'yanova T.R., Kotieva I.M., Kokova L.N., Dodokhova M.A., AndreevaV.O., Puzikova O.Z., Popova V.A., Sozaeva D.I. Rehabilitation therapy in asthma: focus on high-resistance breathing exercises. Russian Medical Inquiry. 2024;8(3):143–149 (in Russ.). DOI: 10.32364/2587-6821-2024-8-3-4.

A decision-making model for prediction of a stable disease course in chronic hepatitis B patients

Patients with chronic hepatitis B (CHB) are regularly monitored for HBV DNA and liver enzymes in order to assess disease progression and the need for antiviral therapy. Identifying patients with a stable course of disease can potentially prolong the intervals between visits, withhold unnecessary tests and save money. Accordingly, we aimed to find predictors for a stable disease course in patients with CHB. 579 patients with CHB, who were followed in a tertiary referral center between January 2004–December 2018, were retrospectively analyzed. Patients with low and steady viral load titer (< 2000 IU/ml) and normal ALT levels (< 40 IU/ml) in 6 consecutive clinic encounters were considered to have a stable course of CHB. A stepwise multivariate logistic regression analysis and a decision tree model were used to identify predictors of a stable disease course. Following exclusion of ineligible patients, a total of 220 patients were included in the final analysis. 64/220 patients had a stable disease course. Patients with a stable disease were older (62.99 ± 12.36 Vs. 54.07 ± 13.64, p < 0.001) with a higher percentage of women (53% vs. 38%) and had lower baseline levels of AST, ALT and viral load (VL). In a multivariate analysis, age (OR 0.94, 95% CI 0.91–0.98), baseline ALT (OR 1.06, 95% CI 1.01–1.1) and VL (OR 1.05 95% CI 1.02–1.08), were significantly associated with a stable disease. In a decision tree model, patients 46–67 years old, with baseline VL < 149 IU/mL and ALT < 40 IU/mL had the best probability (91%) for a stable disease course over 4.4 ± 2.2 years. We conclude that integrating patients’ age with baseline VL and ALT can predict a stable disease course in patients with CHB off treatment.

A biopsy-based pilot clinical study: monitoring the effectiveness of tafamidis treatment of patients with transthyretin amyloid cardiomyopathy

Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is a rare and progressive disease associated with high mortality. It is caused by the accumulation of TTR amyloid protein in various tissues, including the myocardium. Tafamidis is currently the only approved therapy for ATTR-CM. The results of the phase III ATTR-ACT trial showed lower rates of mortality and hospitalization, besides lower rate of decline for both quality of life (QoL), and 6-minute walk test (6mwt) distance [1]. Whether the reported clinical outcomes represent a change in myocardial ATTR-accumulation and remodeling remains unclear. Here we monitor the clinical outcome and the corresponding myocardial histological changes of tafamidis-treated patients using endomyocardial biopsy (EMB). Methods Eleven patients with EMB-proven ATTR-CM, 10 wild type, 1 hereditary, 9 males, 2 females age= 77±9 years, were prescribed with 61 mg tafamidis once daily indefinitely. The course of the disease was evaluated via EMB, 99mTc-DPD scintigraphy, cardiac magnetic resonance imaging (cMRI), echocardiography, 6mwt, Minnesota QoL questionnaire and serum N-terminal pro brain natriuretic peptide (NT-proBNP) analysis, at baseline and after 321±72 days of treatment (ethics application number EA2/140/16). EMBs were examined via immunohistochemistry and Imaging mass spectrometry. All patients received standard heart failure medications. Paired clinical measurements were compared via paired t test for parametric data or Wilcoxon rank test for non-parametric data. Results Following the course of treatment, EMB ATTR-positive area measured via immunohistochemistry increased by 7.7±9.5% (p&amp;lt;0.05). Myocardial CD3+ and CD68+ cell counts remained within normal limits. The EMB peak intensities of ATTR, collagen and macrophage migration inhibitory factor, measured via imaging mass spectrometry were increased by 23% (AUC= 0.677, p&amp;lt;0.001), 25% (AUC= 0.620, p&amp;lt;0.001) and 18% (AUC= 0.609, p&amp;lt;0.001), respectively. Echocardiography measured left ventricular (LV) ejection fraction and LV end-diastolic diameter, as well as 6mwt distance, QoL and serum NT-proBNP showed no significant changes. cMRI did not show any significant changes in fibrosis/amyloidosis markers (N=9). 99mTc-DPD scintigraphy-derived Perugini score (N=10) improved by one-point in two patients and remained stable in the rest. The New York Heart Association (NYHA) functional class improved in one patient and remained stable in 10/11 patients. Conclusion Our findings demonstrate, for the first time, the persistence of myocardial ATTR-accumulation and remodeling despite a clinically stable disease course. Whether this finding is relevant in terms of disease-progression or indicate a need for more intensive treatment warrants further investigation.

Functional Activity of Blood Neutrophils in Patients with Stable Course and Exacerbation of Chronic Obstructive Pulmonary Disease.

We performed a comparative study of the parameters of chemiluminescence of blood neutrophils in patients with different severity of chronic obstructive pulmonary disease in its different periods. The maximum values of induced and spontaneous chemiluminescence were recorded at moderate severity of the disease during exacerbation. Low levels of chemiluminescence indicators were found in severe chronic obstructive pulmonary disease in the stable phase. The values of the induction period of the chemiluminescent response in patients with moderate chronic obstructive pulmonary disease were higher than in the control group. Correlations between the values of induced chemiluminescence of neutrophils and the respiration function parameter FEV1 were established, which may indicate the influence of multidirectional changes in the functional activity of systemic neutrophils on the development and worsening of airway obstruction in chronic obstructive pulmonary disease patients.

Medication persistence among people with multiple sclerosis in Slovenia treated with dimethyl fumarate

Objective Multiple sclerosis is a chronic, demyelinating inflammatory disease of the central nervous system. Medication persistence is defined as an interval between the initiation and last dose of the applied medication and presents a useful surrogate marker of a stable disease course. This observational study aimed to evaluate medication persistence and discontinuation reasons in Slovenian people with multiple sclerosis treated with dimethyl fumarate. Methods Our retrospective cohort study evaluated people with relapsing-remitting multiple sclerosis treated with dimethyl fumarate as an initial monotherapy or switched from injectable disease-modifying therapy medication between 2014 and 2021. Medication dispenses were extracted from the Slovenian National Institute of Public Health Outpatient Medication Database. The medication persistence criterion was based on the treatment gap. Patients exceeding a 60-day gap were considered nonpersistent. The median time to discontinuation was assessed using survival analyses. Considering discontinuation reasons, patients were further divided into safety and inefficacy groups. Due to the high probability of adverse effects, patients exceeding a 60-day gap were included in the safety group, but definite discontinuation reason remains unknown. The impact of covariates was evaluated by Cox regression. Results A total of 269 patients were included (183 women, mean age 37 years). During the 7-year follow-up period, 123 (45.7%) patients discontinued treatment. The median time to discontinuation was 5.6 years. After 1, 2, and 5 years of treatment, 84%, 77%, and 57% of patients were found to be persistent, respectively. All patients older than 30 years (p = 0.0013) and among them, those in the inefficacy group (p = 0.037) were more likely to be persistent. Conclusions The results of our study proved a high persistence rate among our patients. The most frequent discontinuation reason was gastrointestinal adverse effects. Medication persistence requires interventions in younger patients with an unstable disease course.

Delineation of clinical course, outcomes, and prognostic factors in patients with T-cell prolymphocytic leukemia.

T-cell prolymphocytic leukemia (T-PLL) is a rare, post-thymic T-cell neoplasm with a diverse clinical course. T-PLL is typically associated with a poor prognosis; however, a subset of patients have inactive disease on initial presentation. There is a lack of accurate delineation of the disease based on initial clinical presentation and pathological assessment, hindering clinical decision-making. To characterize and delineate disease subtypes based on initial clinical presentation and pathologic assessment, we retrospectively reviewed 81 patients with T-PLL treated at our institution. We compared patients with T-PLL who initially presented with a relatively indolent or stable disease course to those with an aggressive disease course. Clinicopathologic characteristics, overall survival (OS), and prognostic factors were analyzed. Patients with inactive disease had a significantly longer OS than patients with active disease. At diagnosis, presence of B symptoms, low hemoglobin, low platelet count, lymphocyte doubling time of fewer than 3 months, and abnormal cytogenetics were associated with shorter OS. Cell morphology, immunophenotype, absolute lymphocyte count, lactate dehydrogenase levels, involvement of liver, spleen, skin or central nervous system, presence of TCL1 rearrangement or inv (14)/t(14;14), presence of chromosome 8 abnormalities, and presence of deletion of 11q were not associated with significant OS difference among the patients. Receiving alemtuzumab as first-line treatment and consolidation with allogeneic hematopoietic stem cell transplant were associated with better outcomes. T-PLL inactive and active disease subtypes can exhibit overlapping yet different clinical and pathological features. We describe several prognostic factors at diagnosis that can be used for risk stratification and aid in guiding treatment decisions.

A Case of Successful Medical Treatment of Ventricular Tachycardia in a Patient With Ischemic Heart Disease and Heart Failure

The pathogenetic mechanisms of arrhythmias, including high-grade ventricular arrhythmias (including non-sustained ventricular tachycardia), in patients with coronary heart disease may be different. Therefore, the characteristics of ventricular arrhythmias must be considered based on the totality of data, taking into account all the available features. The importance of a personalized approach to the management of a patient with coronary heart disease who had extensive myocardial infarction 18.5 years ago, followed by mammary coronary artery bypass grafting, aneurysmectomy and the development of heart failure with a low ejection fraction, in whom ventricular arrhythmias occurred against the background of a stable course of coronary disease , but after emotional stress, is reflected in this work. An extended examination, as well as a detailed study of the nature of ventricular arrhythmias, made it possible to determine the main provoking factor and select an individualized pathogenetic treatment with a good antiarrhythmic result that persists for several years of observation. Conducting mental tests and psychological questioning can be recommended for patients with coronary heart disease and chronic heart failure as an additional examination to assess the contribution of the psycho-emotional factor to arrhythmogenesis after excluding the ischemic and sympathetic nature of ventricular ectopia. It is incorrect to consider that all ventricular arrhythmias in patients with coronary heart disease are ischemic in nature, and in some clinical situations this statement is even erroneous.

Attenuation of immune activation in patients with multiple sclerosis on a wheat-reduced diet: a pilot crossover trial.

Western lifestyle has been associated with an increase in relapsing-remitting multiple sclerosis (RRMS). In mice, dietary wheat amylase-trypsin inhibitors (ATIs) activate intestinal myeloid cells and augment T cell-mediated systemic inflammation. The aim of this study was to assess whether a wheat- and thus ATI-reduced diet might exert beneficial effects in RRMS patients with modest disease activity. In this 6-month, crossover, open-label, bicentric proof-of-concept trial, 16 RRMS patients with stable disease course were randomized to either 3 months of a standard wheat-containing diet with consecutive switch to a > 90% wheat-reduced diet, or vice versa. The primary endpoint was negative, as the frequency of circulating pro-inflammatory T cells did not decrease during the ATI-reduced diet. We did, however, observe decreased frequencies of CD14+ CD16++ monocytes and a concomitant increase in CD14++ CD16- monocytes during the wheat-reduced diet interval. This was accompanied by an improvement in pain-related quality of life in health-related quality of life assessed (SF-36). Our results suggest that the wheat- and thus ATI-reduced diet was associated with changes in monocyte subsets and improved pain-related quality of life in RRMS patients. Thus, a wheat (ATI)-reduced diet might be a complementary approach accompanying immunotherapy for some patients. German Clinical Trial Register (No. DRKS00027967).

Multiple Sklerose: Änderung im Patientenmanagement während der COVID-19-Pandemie

The coronavirus disease 2019 (COVID-19) pandemic has been a worldwide challenge for the health system. Beside direct effects, it influenced the medical care and treatment of chronic diseases such as multiple sclerosis (MS). During the beginning of the pandemic, the prescription of disease-modifying treatments (DMT) in particular highly effective immunosuppressive drugs was also reduced in Austria and other European countries. Due to increasing evidence, several recommendations were published by national and international societies regarding COVID-19, DMT, and COVID-19 vaccination. In the case of a stable MS disease course, ongoing DMT should be continued. If a new DMT is started or treatment has to be changed, as before the pandemic, the individual risk–benefit has to be evaluated. Furthermore, COVID-19 vaccination is also recommended in untreated and treated patient (currently available vaccine, November 2022). Several healthcare centers have implemented telemedicine during the pandemic and in addition to regular visits, it has been proven to be successful.

A sporadic case of holocord tuberculous transverse myelitis with arachnoiditis

Abstract Background Tubercular infection of the brain and spine is relatively common in endemic regions of the world. Central nervous system tuberculosis can have varied manifestations. The familiar imaging findings are hydrocephalus, ring-enhancing tuberculomas, and meningeal enhancement, having a preference for basal regions. Myelitis is the most common imaging manifestation of spine, with holocord involvement being a rare presentation, as seen in our case. Case presentation We present a case of a pediatric patient undergoing treatment for a tubercular infection of the brain. The patient developed acute onset quadriparesis, manifesting as holocord transverse myelitis on imaging. The imaging findings in the brain manifested as basal meningeal enhancement and non-communicating hydrocephalus, managed by shunt placement. As of the latest, the patient is on follow-up and has a stable disease course. Clinical and laboratory investigations excluded other infectious and non-infectious causes of transverse myelitis, including neuromyelitis optica spectrum disorders. Conclusions Longitudinally extensive transverse myelitis is a rare complication of tubercular myelitis seen as a long-segment signal abnormality with swelling of the cord and corresponding post-contrast enhancement. Involvement of the entire cord is rare, with a handful of cases reported in the literature.

FP.04 Three-year natural history study in Becker muscular dystrophy in The Netherlands

The slow and highly variable disease progression observed in BMD stresses the need to develop outcome measures for clinical trials. We evaluated the responsiveness of different assessments in a cohort of adult BMD patients followed for 3 years. We included 36 genetically confirmed BMD patients (median age at baseline 42.3 years, range 18.6-67.3) of whom 28 were ambulant at baseline (78%). We conducted ambulatory assessments (6WMT, NSAA, 10-meter walk velocity (TMWv), time to rise from floor velocity (TRFv)), PUL1.2 and bilateral maximal voluntary isometric contraction (grip, knee/hip/elbow flexion and extension). The median change and the standard response mean (SRM) at 1- and 3-year follow-up were calculated. Sample sizes (SS) were calculated assuming 50% reduction in disease progression over a 3 year clinical trial with 1:1 randomization. We observed a large variability across all measures, for example the median at baseline for the 6MWT was 439.10m (range 84.30 to 650.00), median change at 1 year follow-up -8.15 (-151.90 to 182.22) and at 3-years -14.50(-151.90 to 158.72). After 1-year follow-up, the SRM was below 0.8 for all considered outcomes. At 3-year follow-up, TMWv and TRFv showed a responsiveness with SRM above 0.8 (1.91, SS 17 and -0.90, SS 79 respectively). Three strength measurements showed SRM >0.8: right elbow flexion (SRM = -1.01, SS 62), left elbow flexion (SRM = -0.85, SS 88) and left hip flexion (SRM = -0.81, SS 96). Of the 29 patients who completed the PUL1.2 at 3rd year follow-up visit, 20 (69%) obtained the maximum score of 74 points. Only one patient lost ambulation during the study. BMD is hallmarked by large inter-individual variability at baseline and follow-up. A relatively stable disease course is common even with 3 years. The ceiling effect of the PUL1.2 illustrates the need for adequate outcome measures in non-ambulant patients.

Correlation between patient-reported manual ability and three objective measures of upper limb function in people with multiple sclerosis.

Upper limb (UL) function is often affected in people with multiple sclerosis (PwMS) and is typically assessed through objective measures, including the Nine Hole Peg Test (9-HPT), Box and Block Test (BBT), and Hand Grip Strength (HGS). It is important to include the subjective perspective of PwMS in the assessment. This study aims to evaluate associations between Manual Ability Measure-36 (MAM-36) and 9-HPT, BBT, and HGS in MS. The cross-sectional study included five Italian centers. Inclusion criteria were age ≥ 18 years, MS diagnosis, and stable disease course. Exclusion criteria were bilateral UL paralysis, and concomitant orthopedic or neurological diseases. A total of 199 PwMS were included: 128 female, mean age=50.7± 13.0 years, 119 relapsing-remitting MS (RRMS), 31 primary and 49 secondary progressive MS, mean disease duration=14.0± 10.4, years, mean Expanded Disability Status Scale (EDSS)=4.6± 2.0. The MAM-36 showed small correlations with 9-HPT, BBT, and HGS. Correlations between MAM-36 and 9-HPT and BBT were highest among subjects with EDSS ≥ 6 and progressive MS. MAM-36 and HGS showed the highest correlations in subjects with EDSS ≤ 5 and RRMS. Combining 9-HPT and HGS provided the strongest predictive power over the MAM-36. Correlations between objective measures and MAM-36 were small to moderate, meaning that objective measures do not match subjects' perception of UL function. The combination of 9-HPT and HGS measures can help improve the assessment of UL function in activities of daily living.