AIMS: The aim of this study was to evaluate the association of serum neurofilament heavy chain (sNfH) and chitinase 3-like 1 (sCHI3L1) with treatment response and disease activity in multiple sclerosis (MS). METHODS: This single-center, prospective, observational cohort study was conducted at the MS Centre, University Hospital Ostrava, Czech Republic, from May 2020 to August 2023. sNfH and sCHI3L1 were determined using ELISA. A mixed-effects linear model with a log-transformed outcome variable was applied. RESULTS: We analyzed 459 samples from 57 people with MS. Patients were sampled an average of 8.05 times during 21.9 months of follow-up. Those experiencing a relapse at sampling had a sNfH concentration 50 % higher than those in remission (exp(β) 1.5, 95 % CI 1.15-1.96). A longer duration of treatment was associated with lower sNfH (exp(β) 0.95, 95 % CI 0.94-0.96). Patients switched from low- to high-efficacy disease-modifying therapies (DMTs) had higher sNfH than patients treated with low-efficacy DMTs only (exp(β) 1.95, 95 % CI 1.35-2.81). Higher sCHI3L1 was associated with older age (exp(β) 1.01, 95 % CI 1.00-1.02) and longer DMT use (exp(β) 1.01, 95 % CI 1.00-1.02). sCHI3L1 values were not associated with relapse at the time of sampling, renal function, sex, or type of DMT. CONCLUSION: In contrast to sCHI3L1, sNfH may be a potential biomarker for monitoring treatment response and confirming clinical relapse in MS. Further research is needed to determine the long-term dynamics of sNfH and develop related treatment strategies.

• Klíčová slova
• Chitinase 3-like 1, ELISA, Multiple sclerosis, Neurofilament heavy chain,
• MeSH
• biologické markery * krev   MeSH
• dospělí MeSH
• hodnocení výsledků zdravotní péče MeSH
• imunologické faktory aplikace a dávkování   farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• neurofilamentové proteiny * krev   MeSH
• prospektivní studie MeSH
• protein CHI3L1 * krev   MeSH
• roztroušená skleróza krev   farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• biologické markery * MeSH
• CHI3L1 protein, human MeSH Prohlížeč
• imunologické faktory MeSH
• neurofilament protein H MeSH Prohlížeč
• neurofilamentové proteiny * MeSH
• protein CHI3L1 * MeSH

BACKGROUND: Waldenström macroglobulinemia (WM) is a lymphoplasmocytic lymphoma with immunoglobulin M monoclonal protein. The incidence of this disease is very low (0.4/100,000), so that this disease can be regarded as an orphan's disease. It means that new drugs are often tested and registered for more frequent diseases. PURPOSE: In this review we will focus on the efficacy of the new drugs for WM. RESULTS: The current treatment options for symptomatic WM patients include alkylating agent cyclophosphamide and anti-CD20 monoclonal antibodies. Therapy with rituximab and bendamustin resulted in longer therapeutic response then therapy with rituximab, cyclophosphamide and dexamethasone. Many drugs, used in multiple myeloma (MM), shoved promising results in WM patients. Bortezomib is effective in WM, but its neurotoxicity is higher in WM than in MM patients. Therefore, new proteasome inhibitors, carfilzomib and ixazomib, are better tolerated as documented in several studies. New types of antiCD20 antibody (obinutuzumab) can be used in patients with rituximab intolerance. in five of our patients with WM, obinutuzumab and bendamustin reached deeper responses than therapies administered in previous lines of therapy. Oral Bruton tyrosine kinase (BTK) inhibitor ibrutinib alone and in combination with rituximab have extended the treatment options for WM patients. New BTK inhibitors (e. g. acalabrutinib, zanubrutinib, and vecabrutinib) were tested and their lower toxicity (atrial fibrillation) was documented. Moreover, the BCL2 inhibitor venetoclax is newly tested. CONCLUSION: New antiCD20 antibody (obinutuzumab) is of advantage in patients with WM with rituximab intolerance as well as bendamustin and new proteasome inhibitors (ixazomib and carfilzomib) or new BTK inhibitors with lower cardiotoxicity. Many of the abovementioned drugs do not have official registration for WM and can be administrated with the consent of the health care provider only. Thus, this work brings evidence of their efficacy.

• Klíčová slova
• Waldenström macroglobulinemia, bendamustin, carfilzomib, ibrutinib, ixazomib, obinutuzumab,
• MeSH
• bendamustin hydrochlorid terapeutické užití   MeSH
• cyklofosfamid terapeutické užití   MeSH
• inhibitory proteasomu terapeutické užití   MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• protinádorové látky * terapeutické užití   MeSH
• rituximab terapeutické užití   MeSH
• Waldenströmova makroglobulinemie * diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• bendamustin hydrochlorid MeSH
• cyklofosfamid MeSH
• inhibitory proteasomu MeSH
• ixazomib MeSH Prohlížeč
• monoklonální protilátky MeSH
• protinádorové látky * MeSH
• rituximab MeSH

BACKGROUND: Idiopathic multicentric Castleman disease (iMCD) is characterized by constitutional symptoms, enlarged lymph nodes and laboratory test abnormalities, which are primarily related to the overproduction of interleukin-6 (IL-6). This form (iMCD) was treated earlier with cytostatics used for lymphoma, later with bio-logic therapy as rituximab, immunodulatory drugs and proteasome inhibitors, and in the last years with an anti-IL-6 antibody, siltuximab. Siltuximab is a human-mouse chimeric immunoglobulin G1k monoclonal antibody against human IL-6 approved in the European Union for the treatment of iMCD. In view of the limited treatment options for iMCD, this case report aimed to evaluate the efficacy and safety of siltuximab in the management of this condition. CASE: We describe a young woman with iMCD diagnosed at the age of 25 years. For first line treatment, rituximab and dexamethasone were used without any cytostatic because the patient wished to give birth to a healthy child in the future. However, the response after this first line therapy was short. In addition, after 3 years from the start of rituximab + dexamethasone therapy, it was necessary to administer treatment for the relapse of iMCD. We decided for siltuximab in this young woman, still aged < 30 years, and started administration of siltuximab in 3-week intervals. RESULTS: After administration of first two infusions of siltuximab, all inflammatory markers returned to normal value. Moreover, serum hemoglobin and albumin levels as well as C-reactive protein normalized after the first two administrations of siltuximab. The clinical response continue, siltuximab is still administered in 3-week intervals. PET/CT with fluorodeoxyglucose confirmed a very good anatomic and metabolic response to the treatment. Siltuximab demonstrated a favorable safety profile, and the prolonged treatment was well tolerated. CONCLUSION: This result is encouraging and demonstrates the potential of siltuximab as treatment of CD. As earlier published, this case confirms that significantly elevated inflammatory markers in a patient with CD predict a good response to siltuximab.

• Klíčová slova
• idiopathic multicentric Castleman‘s disease, interindividual biological variation, interleukin-6, siltuximab,
• MeSH
• cytostatické látky * MeSH
• dexamethason MeSH
• dospělí MeSH
• hyperplazie velkých lymfatických uzlin * farmakoterapie   MeSH
• imunosupresiva MeSH
• interleukin-6 MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• PET/CT MeSH
• rituximab terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH
• Názvy látek
• cytostatické látky * MeSH
• dexamethason MeSH
• imunosupresiva MeSH
• interleukin-6 MeSH
• monoklonální protilátky MeSH
• rituximab MeSH
• siltuximab MeSH Prohlížeč

BACKGROUND: Serum neurofilaments (sNfs), especially the most investigated serum neurofilament light chain (sNfL), are promising biomarkers in multiple sclerosis (MS). However, their clinical utility is still limited, given the availability and costs of accessible analytical methods. The gold standard for the detection of sNfs is represented by the single molecule arrays (SIMOA). Recently, a high sensitivity enzyme-linked immunosorbent assay (hsELISA) has also been introduced. The objective of the study was to compare both assays for the determination of sNfL and neurofilament heavy chain (sNfH) concentrations in a defined MS cohort. The second objective was to identify contributing factors to sNfs concentrations determined by hsELISA. METHODS: Serum samples were collected from MS patients attending the MS Centre, University Hospital Ostrava, Czech Republic. The levels of sNfs were detected using SIMOA and hsELISA assays. RESULTS: The Spearman's rank correlation coefficient between the sNfL SIMOA and sNfL hsELISA and between the sNfH SIMOA and sNfH hsELISA was moderate rs= 0.543 (p = 0.001) and rs= 0.583 (p = 0.001), respectively. The Passing-Bablok regression analysis demonstrated bias between both methods. Equally significant bias between the methods was confirmed by the Bland-Altman plots. Furthermore, confounding factors affecting the sNfL levels were glomerular filtration rate (eGFR; 95% CI -2.34 to -0.04) and sex (95% CI -2.38 to -0.10). The sNfH levels were affected by age (95% CI 0.01 to 0.07), eGFR (95% CI -2.45 to -0.02), body mass index (BMI; 95% CI -0.31 to -0.05), and blood volume (95% CI 0.69 to 3.35). CONCLUSION: This analytical study showed significant differences between hsELISA and SIMOA methods, especially for the sNfH concentrations. We identified confounding factors for sNfs levels determined by hsELISA. The sNfs levels were influenced by renal function and sex, whilst sNfH levels were affected by age, BMI, and total blood volume.

• Klíčová slova
• High sensitivity ELISA, Multiple sclerosis, Neurofilament heavy chain, Neurofilament light chain, SIMOA,
• MeSH
• biologické markery MeSH
• ELISA MeSH
• intermediární filamenta * MeSH
• lidé MeSH
• roztroušená skleróza * diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• biologické markery MeSH

BACKGROUND: Gamma-heavy chain disease is a rare disease, described so far in approximately 150 cases. The aim of this work was laboratory dia-gnostics of immunoglobulin heavy chain disease. MATERIALS AND METHODS: A 60-year-old patient was referred to the University Hospital in Ostrava for suspected marginal zone lymphoma from gastric bio-psy. Staging examinations including bone marrow trepanobio-psy and PET/CT were added; special examinations required serum protein electrophoresis, immunofixation electrophoresis, determination of polyclonal immunoglobulins, free light chains, and immunoglobulin heavy/light chain pairs. Isoelectric focusing in agarose gel followed by affinity immunoblotting and SDS electrophoresis was added due to unclear findings. RESULTS: 0.1 % of plasma cells were found in the bone marrow, of which 87 % were clonal (pathological) plasma cells, followed by the cyt cytotype LAMBDA + CD38 + CD138 + CD45 + CD19 + CD56- CD27 + CD81- CD117-. Monoclonal heavy chains were found in the patients serum. No monoclonal immunoglobulin heavy or light chains were detected in urine. The PET/CT examination showed generalized lymphadenopathy, splenomegaly and inhomogeneous accumulation of fluorodeoxyglucose in axillary and appendicular skeleton, but without the presence of typical osteolytic lesions. CONCLUSION: Monoclonal heavy chains of immunoglobulins are a rare disease. In contrast to the detection of a complete paraprotein molecule, additional methods must be used to confirm them. The finding of monoclonal heavy chain gamma in the serum of the study patient is related to the presence of marginal zone lymphoma, which was proven from a gastric bio-psy. The study was supported by the project of MH CZ - DRO - FNOs /2017 (Biobank in Teaching Hospital Ostrava) The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

• Klíčová slova
• SDS electrophoresis, electrophoresis, heavy chain disease, immunofixation electrophoresis, isoelectric focusing,
• MeSH
• imunoglobuliny - gama-řetězce krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoc z těžkých řetězců krev   diagnóza   MeSH
• prognóza MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• imunoglobuliny - gama-řetězce MeSH

• MeSH
• alemtuzumab škodlivé účinky   MeSH
• dospělí MeSH
• elektromyografie MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• nemoci periferního nervového systému chemicky indukované   diagnostické zobrazování   MeSH
• nervové vedení účinky léků   fyziologie   MeSH
• protinádorové látky imunologicky aktivní škodlivé účinky   MeSH
• roztroušená skleróza diagnostické zobrazování   farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• kazuistiky MeSH
• Názvy látek
• alemtuzumab MeSH
• protinádorové látky imunologicky aktivní MeSH

OBJECTIVE: To compare cytologic findings in cerebrospinal fluid (CSF) in various subgroups of multiple sclerosis (MS) patients. STUDY DESIGN: CSF from 77 patients with clinically definitive or probable MS was examined by means of qualitative cytology. After the cell count was determined in a Fuchs-Rosenthal chamber, slides were prepared by the cytosedimentation method and stained with May-Grünwald-Giemsa stain and oil red O and, whenever possible, with Papanicolaou stain and toluidine blue. In addition to the differential cell count, the lymphocyte/monocyte ratio, percentage of activated forms in the lymphocytic and monocytic series, presence and percentage of lymphoplasmacytes and mature plasma cells, presence of lipophages, lymphophages and presence of mitotic figures were evaluated. RESULTS: The following statistically significant differences were found between the various MS subgroups: (1) higher prevalence of mitotic figures in the primary progressive MS subgroup; (2) higher prevalence of foam cells and lymphophages and lower prevalence of CSF pleocytosis in more severely disabled patients; (3) lower cell count, lower prevalence of CSF pleocytosis, lower lymphocyte/monocyte ratio and lower prevalence of lymphoplasmacytes in treated patients; and (4) higher prevalence of mature plasma cells and lipophages in MS patients with disease of longer duration. CONCLUSION: The differences observed in the various MS subgroups may reflect certain aspects of MS pathogenesis. Qualitative CSF cytology may therefore be useful for both clinicians and neuroimmunologists. Qualitative cytology of CSF is an important diagnostic method that should never be omitted from an examination of CSF from patients with MS.

• MeSH
• aktivace lymfocytů MeSH
• aktivace makrofágů MeSH
• dospělí MeSH
• leukocytóza imunologie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrofágy imunologie   ultrastruktura   MeSH
• mitóza MeSH
• monocyty imunologie   MeSH
• mozkomíšní mok cytologie   imunologie   MeSH
• pěnové buňky ultrastruktura   MeSH
• plazmatické buňky imunologie   ultrastruktura   MeSH
• počet leukocytů MeSH
• roztroušená skleróza mozkomíšní mok   imunologie   patologie   terapie   MeSH
• senzitivita a specificita MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

OBJECTIVES: To compare cerebrospinal fluid (CSF) and serum transferrin (Tf) concentrations, transferrin quotient and index in various subgroups of MS patients. MATERIAL AND METHODS: CSF and serum transferrin concentrations, transferrin quotient QTf (i.e. CSF transferrin/serum transferrin x 10(3)) and index (QTf/Qalbumin) were determined in a group of 51 patients with clinically definite or probable multiple sclerosis (MS). Patients were subdivided according to the disease form (relapsing-remitting = RR, secondary progressive = SP, primary progressive = PP; patients with RR form were further subdivided into those in the attack and those in remission), disease severity (EDSS 0-5.5, EDSS 6.0-10.0), its treatment (non-treated - including patients treated with vitamins and/ or vasodilators only, treated - i.e. glucocorticoids and/or immunosuppressants and/or (exceptionally) beta-interferon), disease duration (0-2 years, >2-10 years, > 10 years) and sex. Correlation of transferrin values with age was also performed. RESULTS: Serum transferrin was somewhat lower and significantly more frequently subnormal in PP patients in comparison with the SP form and the RR form in remission. Transferrin index was significantly higher in the PP form than in the RR as well as the SP form. Transferrin quotient was significantly more frequently subnormal in patients in remission compared to those in the attack of the RR disease. CSF transferrin as well as transferrin quotient were more frequently subnormal in patients with short disease duration (0-2 years) than in patients with longer disease duration; these parameters, however, correlated also significantly with age. CSF transferrin and transferrin quotient were higher in male than in female patients. CONCLUSION: The authors conclude that evaluation of transferrin in MS patients - along with albumin - may help to differentiate among various MS subgroups, since there are significant differences among RR, SP and PP forms. For this purpose, however, other CSF protein fractions should be evaluated in parallel in order to obtain more complex information and to establish a panel of examinations enabling multiple statistical analyses. Transferrin evaluation in MS may also be of significant theoretical interest, since transferrin is known to be involved in the regulation of iron metabolism and it may have a protective role against the oxidative stress. Moreover, transferrin is a growth factor important for proliferation of activated T lymphocytes. By means of the use of transferrin quotient and especially transferrin index, it may be possible to estimate the proportion of intra-CNS-synthesized transferrin and/or rate of specific transferrin transport across the blood-CSF barrier. Further studies are, however, needed for such an evaluation.

• MeSH
• analýza rozptylu MeSH
• antioxidancia metabolismus   MeSH
• chronicko-progresivní roztroušená skleróza krev   mozkomíšní mok   metabolismus   MeSH
• hematoencefalická bariéra MeSH
• lidé MeSH
• relabující-remitující roztroušená skleróza krev   mozkomíšní mok   metabolismus   MeSH
• roztroušená skleróza krev   mozkomíšní mok   klasifikace   metabolismus   MeSH
• stupeň závažnosti nemoci MeSH
• transferin * analýza   mozkomíšní mok   metabolismus   MeSH
• věkové faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• antioxidancia MeSH
• transferin * MeSH

The authors describe an uncommon and severe intoxication with the mushroom Lepiota Helveolla Bres. which manifested itself by fulminant hepatic failure. The possibility of urgent transplantation of the liver was considered. After conservative treatment the patient recovered, however, completely. In the conclusion the authors' view is discussed as regards indications of urgent transplantation of the liver in intoxications with mushrooms which may cause fulminant hepatic failure.

• MeSH
• dospělí MeSH
• jaterní encefalopatie etiologie   terapie   MeSH
• lidé MeSH
• otrava houbami komplikace   terapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• kazuistiky MeSH