BACKGROUND AND OBJECTIVES: Patients with multiple sclerosis (MS) may demonstrate better disease control when treatment is initiated on high-efficacy disease-modifying therapies (DMTs) from onset. This subgroup analysis assessed the long-term efficacy and safety profile of the high-efficacy DMT ocrelizumab (OCR) as first-line therapy for early-stage relapsing MS (RMS). METHODS: Post hoc exploratory analyses of efficacy and safety were performed in a subgroup of treatment-naive patients with RMS who received ≥1 dose of OCR in the multicenter OPERA I/II (NCT01247324/NCT01412333) studies. Patients were randomized to OCR or interferon β-1a for 96 weeks (double-blind controlled treatment period [DBP]), before switching to OCR in the open-label extension (OLE). Efficacy assessments included no evidence of disease activity (NEDA-3), 24-week confirmed disability progression (CDP), MRI lesion activity, change in whole-brain volume; with safety outcomes assessed over a 9-year treatment period. RESULTS: Overall, 757 patients were included (interferon-treated n = 382, mean age 36.3 years, 65.7% female; OCR-treated n = 375, mean age 35.5 years, 64.0% female); 505 of 757 (66.7%) completed 9 years of follow-up. The difference in NEDA status between OCR-treated and interferon-treated patients achieved during the DBP (72.5% and 43.8%, respectively, odds ratio 3.48, 95% CI 2.52-4.81) was maintained throughout the 7-year OLE (48.2% vs 25.7%; odds ratio 2.72, 95% CI 1.94-3.82). No 24-week CDP was observed in 78.7% of OCR-treated patients over 9 years. Brain volume loss over the entire study period remained numerically higher among patients starting OCR later (p = 0.09 at OLE at week 336). During the DBP, safety profiles in both groups were similar; no new safety signals were observed during the OLE. Over >9 years of continuous OCR treatment, the rate of infections remained low and stable over time. DISCUSSION: A higher proportion of OCR-treated patients achieved NEDA status compared with interferon-treated patients during the DBP, which was maintained throughout the OLE. After switching to OCR, disability accrual and brain volume loss among interferon-treated patients became similar to the OCR-OCR group, but disability and brain volume loss accrued during interferon treatment were not recovered. Possible study limitations include assessment bias due to unmaintained blinding during the OLE. These data support OCR as first-line therapy for these patients. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that OCR delays disease progression in treatment-naïve patients with early-stage RMS.

• MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Antibodies, Monoclonal, Humanized * adverse effects   therapeutic use   administration & dosage   MeSH
• Immunologic Factors * adverse effects   administration & dosage   therapeutic use   MeSH
• Interferon beta-1a therapeutic use   administration & dosage   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Disease Progression MeSH
• Multiple Sclerosis, Relapsing-Remitting * drug therapy   diagnostic imaging   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH

BACKGROUND AND OBJECTIVES: Early treatment of multiple sclerosis (MS) reduces disease activity and the risk of long-term disease progression. Effectiveness of ocrelizumab is established in relapsing MS (RMS); however, data in early RMS are lacking. We evaluated the 4-year effectiveness and safety of ocrelizumab as a first-line therapy in treatment-naive patients with recently diagnosed relapsing-remitting MS (RRMS). METHODS: ENSEMBLE was a prospective, 4-year, international, multicenter, single-arm, open-label, phase IIIb study. Patients were treatment naive, aged 18-55 years, had early-stage RRMS with a disease duration ≤3 years, Expanded Disability Status Scale (EDSS) score ≤3.5, and ≥1 clinically reported relapse(s) or ≥1 signs of brain inflammatory activity on MRI in the prior 12 months. Patients received IV ocrelizumab 600 mg every 24 weeks. Effectiveness endpoints over 192 weeks were proportion of patients with no evidence of disease activity (NEDA-3; defined as absence of relapses, 24-week confirmed disability progression [CDP], and MRI measures, with prespecified MRI rebaselining at week 8), 24-week/48-week CDP and 24-week confirmed disability improvement, annualized relapse rate (ARR), mean change in EDSS score from baseline, and safety. Cognitive status, patient-reported outcomes, and serum neurofilament light chain (NfL) were assessed. Descriptive analysis was performed on the intention-to-treat population. RESULTS: Baseline characteristics (N = 678) were consistent with early-stage RRMS (n = 539 patients, 64.6% female, age 40 years and younger; median age: 31.0 years; duration since: MS symptom onset 0.78 years, RRMS diagnosis 0.24 years; mean baseline EDSS score [SD] 1.71 [0.95]). At week 192, most of the patients had NEDA-3 (n = 394/593, 66.4%), 85.0% had no MRI activity, 90.9% had no relapses, and 81.8% had no 24-week CDP over the study duration. Adjusted ARR at week 192 was low (0.020, 95% CI 0.015-0.027). NfL levels were reduced to and remained within the healthy donor range, by week 48 and week 192, respectively. No new or unexpected safety signals were observed. DISCUSSION: Disease activity based on clinical and MRI measures was absent in most of the patients treated with ocrelizumab over 4 years in the ENSEMBLE study. Safety was consistent with the known profile of ocrelizumab. Although this single-arm study was limited by lack of a parallel group for comparison of outcome measures, the positive benefit-risk profile observed may provide confidence to adopt ocrelizumab as a first-line treatment in newly diagnosed patients with early RMS. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that adult patients with early-stage MS who were treatment naive maintained low disease activity (NEDA-3) over 4 years with ocrelizumab treatment; no new safety signals were detected. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier NCT03085810; first submitted March 16, 2017; first patient enrolled: March 27, 2017; available at clinicaltrials.gov/ct2/show/NCT03085810.

• MeSH
• Adult MeSH
• Antibodies, Monoclonal, Humanized * therapeutic use   adverse effects   administration & dosage   MeSH
• Immunologic Factors * therapeutic use   adverse effects   administration & dosage   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Adolescent MeSH
• Young Adult MeSH
• Disability Evaluation MeSH
• Disease Progression MeSH
• Prospective Studies MeSH
• Multiple Sclerosis, Relapsing-Remitting * drug therapy   diagnostic imaging   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH

BACKGROUND: Ublituximab is a novel anti-CD20 monoclonal antibody glycoengineered for enhanced antibody-dependent cellular cytotoxicity. The phase 3 ULTIMATE I and II studies showed significant improvements in annualized relapse rate, total number of gadolinium-enhancing (Gd+) T1 lesions, and total number of new or enlarging T2 at Week 96, as well as improvement in the proportion of participants with no evidence of disease activity (NEDA) from Weeks 24-96 with ublituximab vs. teriflunomide. METHODS: In ULTIMATE I (NCT03277261; www.clinicaltrials.gov) (N = 549) and II (NCT03277248; www.clinicaltrials.gov) (N = 545), participants with relapsing multiple sclerosis received ublituximab 450 mg intravenous infusion every 24 weeks (following Day 1 infusion of 150 mg and Day 15 infusion of 450 mg) or teriflunomide 14 mg oral once daily for 96 weeks. Pooled post hoc analyses evaluated NEDA by treatment epoch and participant subtype: age ( ≤ 38 or >38 years), early or later disease (<3 or ≥3 years following diagnosis), treatment history (treatment naïve or previously treated), 0 or ≥1 Gd+ T1 lesions at baseline, and Expanded Disability Status Scale score ≤ 3.5 or >3.5 at baseline. NEDA was defined as no confirmed relapses, no Gd+ T1 lesions, no new or enlarging T2 lesions, and no disability progression confirmed for ≥12 weeks. RESULTS: NEDA rates in the ublituximab vs. teriflunomide cohorts by treatment epoch were: Weeks 0-96, 44.6% vs. 12.4% (3.6 × improvement); Weeks 24-96 (re-baselined), 82.1% vs. 22.5% (3.6 × improvement); and Weeks 48-96 (re-baselined), 88.2% vs. 30.4% (2.9 × improvement) (all p < 0.0001). The primary driver of disease activity in ublituximab-treated participants was new or enlarging T2 lesions during Weeks 0-24. 41.8% of ublituximab-treated participants who had evidence of disease activity in the first year (Weeks 0-48) experienced NEDA in the second year of treatment (Weeks 48-96) compared with 17.3% of teriflunomide-treated participants. At Weeks 24-96 (re-baselined), rates of NEDA were significantly higher with ublituximab than teriflunomide in all participant subtypes (all p < 0.0001). CONCLUSIONS: ULTIMATE I and II pooled post hoc analyses demonstrated a consistent NEDA benefit among ublituximab-treated participants across treatment epochs and key participant subpopulations.

• Publication type
• Journal Article MeSH

V programu surveillance byl v roce 2023 zjištěn v České republice pokles počtu invazivních meningokokových onemocnění oproti předchozímu roku: celkem 16 (nemocnost 0,15/100 000 obyv.) proti 25 v roce 2022 (nemocnost 0,24/100000 obyv.). Z 16 onemocnění v roce 2023 jedno skončilo úmrtím – celková smrtnost 6,25 %. Toto úmrtí způsobila séroskupina Y ve věkové skupině nad 65 let věku. Podobně jako v předchozím roce převažovala i v roce 2023 onemocnění způsobená Neisseria meningitidis B (8 ze 16), čtyři onemocnění byla způsobená séroskupinou C a po jednom onemocnění způsobily séroskupiny A aY. U dvou případů nebyla séroskupina určena: N. meningitidis ND. V roce 2023 došlo ve srovnání s předchozím rokem k výraznému poklesu nemocnosti v nejmladší věkové skupině 0–11měsíčních (na 1,96/100 000 z 5,37/100000 obyv.). Nemocnost v nejmladší věkové skupině klesla u onemocnění způsobeného séroskupinou B (na 0,98/100 000 z 3,58/100000 obyv.) i u séroskupin preventabilních konjugovanou tetravakcínou A, C, W, Y (na 0,98/100 000 z 1,79/100000 obyv.). Ve věkové skupině 1–4letých nemocnost v roce 2023 mírně klesla oproti předchozímu roku (na 0,43/100 000 z 0,67/100000 obyv.) a byla způsobena pouze séroskupinou B. Ve věkové skupině 15–19 letých v roce 2023 nemocnost poklesla oproti předchozímu roku (na 0,18/100 000 z 0,79/100 000 obyv.) a byla rovněž způsobena pouze séroskupinou B. Z 16 invazivních meningokokových onemocnění v roce 2023 bylo 9 prokázáno pouze kultivačně, 2 kultivačně a metodou PCR, 5 pouze metodou PCR. V roce 2023 byla v Národní referenční laboratoři provedena multilokusová sekvenční typizace (MLST) u všech 9 kmenů z invazivního meningokokového onemocnění, které byly do NRL pro meningokokové nákazy poslány. MLST prokázala heterogenitu izolátů způsobujících IMO: celkem bylo zjištěno 5 hypervirulentních klonálních komplexů, z nich nejčastější byl cc103 (3 izoláty), následovaný cc11, cc213, cc23 a cc41/44 (vždy po jednom izolátu). MLST analýze byl podroben také jeden izolát od kontaktu s IMO s výsledkem cc103.

In the surveillance programme, a decrease in the number of invasive meningococcal diseases (IMD) was detected in the Czech Republic in 2023 compared to the previous year: a total of 16 (incidence 0.15/100000) compared to 25 in 2022 (incidence 0.24/100000). Of the 16 cases in 2023, one resulted in death – an overall case fatality rate was 6.25%. This death was caused by serogroup Y in the age group over 65 years. As in the previous year, Neisseria meningitidis B accounted for the majority of cases in 2023 (8 out of 16), four cases were caused by serogroup C and one case each by serogroups A and Y. In two cases, the serogroup was not determined: N. meningitidis ND. In 2023, there was a significant decrease in the morbidity in the youngest age group 0–11 months (to 1.96/100,000 from 5.37/100,000) compared to the previous year. Morbidity in the youngest age group decreased for serogroup B (to 0.98/100,000 from 3.58/100,000) and for serogroups preventable with conjugate tetravaccine A, C, W, Y (to 0.98/100,000 from 1.79/100,000). In the age group 1–4 years old, the morbidity in 2023 decreased slightly compared to the previous year (to 0.43/100,000 from 0.67/100,000) and was caused only by serogroup B. In the age group 15–19 years old, the morbidity in 2023 decreased compared to the previous year (to 0.18/100 000 from 0.79/100000) and was also due to serogroup B only. Of the 16 invasive meningococcal disease cases in 2023, 9 were proven by culture only, 2 by culture and PCR, and 5 by PCR only. In 2023, multilocus sequence typing (MLST) was performed for all the 9 strains from the invasive meningococcal disease cases sent to the National Reference Laboratory for Meningococcal Infections. MLST demonstrated heterogeneity of the isolates causing IMD: a total of 5 hypervirulent clonal complexes were identified, the most common being cc103 (3 isolates), followed by cc11, cc213, cc23 and cc41/44 (one isolate each). One isolate from the IMD contact was also subjected to MLST analysis with the result of cc103.

• MeSH
• Humans MeSH
• Meningococcal Infections * epidemiology   mortality   prevention & control   MeSH
• Meningococcal Vaccines MeSH
• Neisseria meningitidis isolation & purification   classification   MeSH
• Polymerase Chain Reaction MeSH
• Serogroup MeSH
• Population Surveillance MeSH
• Age Distribution MeSH
• Check Tag
• Humans MeSH
• Publication type
• Chart MeSH
• Geographicals
• Czech Republic MeSH

BACKGROUND AND OBJECTIVES: Retinal optical coherence tomography (OCT) provides promising prognostic imaging biomarkers for future disease activity in multiple sclerosis (MS). However, raw OCT-derived measures have multiple dependencies, supporting the need for establishing reference values adjusted for possible confounders. The purpose of this study was to investigate the capacity for age-adjusted z scores of OCT-derived measures to prognosticate future disease activity and disability worsening in people with MS (PwMS). METHODS: We established age-adjusted OCT reference data using generalized additive models for location, scale, and shape for peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GCIP) thicknesses, involving 910 and 423 healthy eyes, respectively. Next, we transformed the retinal layer thickness of PwMS from 3 published studies into age-adjusted z scores (pRNFL-z and GCIP-z) based on the reference data. Finally, we investigated the association of pRNFL-z or GCIP-z as predictors with future confirmed disability worsening (Expanded Disability Status Scale score increase) or disease activity (failing of the no evidence of disease activity [NEDA-3] criteria) as outcomes. Cox proportional hazards models or logistic regression analyses were applied according to the original studies. Optimal cutoffs were identified using the Akaike information criterion as well as location with the log-rank and likelihood-ratio tests. RESULTS: In the first cohort (n = 863), 172 PwMS (24%) had disability worsening over a median observational period of 2.0 (interquartile range [IQR]:1.0-3.0) years. Low pRNFL-z (≤-2.04) were associated with an increased risk of disability worsening (adjusted hazard ratio (aHR) [95% CI] = 2.08 [1.47-2.95], p = 3.82e-5). In the second cohort (n = 170), logistic regression analyses revealed that lower pRNFL-z showed a higher likelihood for disability accumulation at the two-year follow-up (reciprocal odds ratio [95% CI] = 1.51[1.06-2.15], p = 0.03). In the third cohort (n = 78), 46 PwMS (59%) did not maintain the NEDA-3 status over a median follow-up of 2.0 (IQR: 1.9-2.1) years. PwMS with low GCIP-z (≤-1.03) had a higher risk of showing disease activity (aHR [95% CI] = 2.14 [1.03-4.43], p = 0.04). Compared with raw values with arbitrary cutoffs, applying the z score approach with optimal cutoffs showed better performance in discrimination and calibration (higher Harrell's concordance index and lower integrated Brier score). DISCUSSION: In conclusion, our work demonstrated reference cohort-based z scores that account for age, a major driver for disease progression in MS, to be a promising approach for creating OCT-derived measures useable across devices and toward individualized prognostication.

• MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Tomography, Optical Coherence * MeSH
• Prognosis MeSH
• Disease Progression * MeSH
• Retina diagnostic imaging   pathology   physiopathology   MeSH
• Multiple Sclerosis * physiopathology   diagnostic imaging   MeSH
• Severity of Illness Index MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Aktuální platná úhradová kritéria umožňují lékařům zahájit vysoce efektivní imunomodulační terapii, tzv. HET (high‐efficacy treatment), již od první ataky za předpokladu splnění nepříznivých prognostických známek, kterými jsou přítomnost T1 gadolinium enhancující nebo infratentoriální léze a/nebo spinální léze. Tato možnost poskytuje pacientům obrovskou výhodu, která vede prokazatelně k oddálení nebo minimalizaci rizika progrese nezávislé na relapsech, stejně tak významně redukuje i riziko relapsu a v neposlední řadě taktéž i riziko radiologické progrese. Efektivita vysoce účinné terapie je v rámci článku prezentována v kazuistice pacientky, u níž se pomocí HET podařilo dosáhnout klinické i radiologické stability, a tedy i statusu NEDA‐3.

Current reimbursement rules make it possible for physicians to start the highly effective immunomodulatory therapy (so called HET) of multiple sclerosis since the first attack of the disease when unfavorable prognostic traits are present, i.e. gadolinium‐enhancing T1 or infratentorial and/or spinal lesions. This fact represents an enormous advantage for the patients, clearly postponing or minimizing progression independent of relapses and also reducing significantly the risk of relapse or, last but not least, of radiological progression. In this article, the effectiveness of highly effective therapy is demonstrated by a case study of a female patient in whom both clinical and radiological stability, i.e. NEDA‐3 status, were achieved using HET.

• Keywords
• ofatumumab,
• MeSH
• Adult MeSH
• Antibodies, Monoclonal, Humanized administration & dosage   pharmacology   therapeutic use   MeSH
• Injections, Subcutaneous MeSH
• Humans MeSH
• Multiple Sclerosis * diagnosis   drug therapy   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Publikace se zaměřuje na použití mimotělní membránové oxygenace v operační chirurgii. Určeno odborné veřejnosti.; Extrakorporální membránová oxygenace (ECMO) je invazivní terapeutická metoda zachraňující lidské životy. Metoda prošla intenzivním vývojem a s postupem času přibývá pacientů i indikací k jejímu využití v léčbě kriticky nemocných.

• MeSH
• Surgical Procedures, Operative MeSH
• Extracorporeal Membrane Oxygenation MeSH
• Publication type
• Monograph MeSH

• Conspectus
• Ortopedie. Chirurgie. Oftalmologie
• NML Fields
• chirurgie

Extrakorporální membránová oxygenace (ECMO) je invazivní terapeutická metoda zachraňující lidské životy. Metoda prošla intenzivním vývojem a s postupem času přibývá pacientů i indikací k jejímu využití v léčbě kriticky nemocných.

• Keywords
• Anesteziologie, resuscitace, emergency,
• MeSH
• Surgical Procedures, Operative MeSH
• Extracorporeal Membrane Oxygenation MeSH

• NML Fields
• chirurgie

• Keywords
• ofatumumab, studie ALITHIOS, status NEDA-3,
• MeSH
• Data Analysis MeSH
• Antigens, CD20 pharmacology   therapeutic use   MeSH
• Drug Evaluation methods   MeSH
• Antibodies, Monoclonal, Humanized * pharmacology   classification   therapeutic use   MeSH
• Humans MeSH
• Multiple Sclerosis * drug therapy   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Clinical Study MeSH

Vysokoškolská učebnice, která se zaměřuje na oftalmologii.

• MeSH
• Ophthalmology MeSH

• Conspectus
• Ortopedie. Chirurgie. Oftalmologie
• Učební osnovy. Vyučovací předměty. Učebnice
• NML Fields
• oftalmologie
• NML Publication type
• učebnice vysokých škol