Vlastimil Scudla

N?pln? sd?len? je problematika diferenci?ln? diagnostiky urychlen? sedimentace erytrocyt? (SE) z pohledu intern? medic?ny. Vedle vymezen? pojmu jsou pops?ny technika vy?et?en?, chyby v preanalytick? i analytick? f?zi, referen?n? hodnoty klasic... N?pln? sd?len? je problematika diferenci?ln? diagnostiky urychlen? sedimentace erytrocyt? (SE) z pohledu intern? medic?ny. Vedle vymezen? pojmu jsou pops?ny technika vy?et?en?, chyby v preanalytick? i analytick? f?zi, referen?n? hodnoty klasic...

FN a LF UP v Olomouci Monoklonální gamapatie (MG) jsou vysoce heterogenní skupinou zhoubných, většinou ale nezhoubných stavů, jejichž společným jmenovatelem je přítomnost monoklonálního imunoglobulinu (MIg, "paraproteinu") nebo jeho strukturálních komponent v séru a/nebo v moči. Náplní sdělení je podání přehledu současného spektra nezhoubných MG, jejich účelné diagnostiky a diferenciální diagnostiky z pohledu primární lékařské praxe. Součástí textu jsou rovněž současná diagnostická kritéria vybraných nosologických jednotek, především monoklonální gamapatie nejistého významu (MGUS) včetně jejich podtypů, "monoclonal gammopathy of renal significance" (MGRS), AL-systémové amyloidózy a nemoci z depozice lehkých řetězců imunoglobulinu (LCDD), včetně zhodnocení jejich významu z pohledu běžné klinické praxe. Klíčová slova: monoklonální gamapatie, monoklonální gamapatie nejistého významu, "monoclonal gammopathy of renal significance", Al-systémová amyloidóza, nemoc z depozice lehkých řetězců imunoglobulinu, diferenciální diagnóza. Differential diagnosis of monoclonal gammopathies from the point of clinical practice II. Monoclonal gammopathy of undetermined significance and other monoclonal gammopathies of the "non-malignant" origin Monoclonal gammopathies (MG) are a very heterogeneous group of both malignant and dominantly non-malignant conditions that are characterized by the presence of monoclonal immunoglobulin (MIg, "paraprotein") or its structural components in serum and/or urine. The aim of this paper is to present the spectrum of "non-malignant" MG, their diagnostics and differential diagnostics from the point of primary health care. The paper includes diagnostic criteria of selected nosologocal units, especially monoclonal gammopathy of undetermined significance (MGUS) and its subtypes, monoclonal gammopathy of renal significance (MGRS), AL-amyloidosis and light chain deposition disease (LCDD), including their position in routine clinical practice.

Advances in the diagnosis and treatment of multiple myeloma (MM), place increasing demands on accurate stratification of patients as the starting point for optimal individualized therapy. The present study focused on assessing the association between HLC levels and the HLC-r to parameters of MM activity, prognosis and tumor mass volume.The objective was to assess the correlation of immunoglobulin (Ig), heavy/light chain (HLC) pairs (IgG-κ and-λ, IgA-κ and -λ HLC) and the ratio of monoclonal involved-HLC (i-HLC) to polyclonal uninvolved (u-HLC) Ig concentrations assessed by the Hevylite(TM) method with the free light chain κ/λ ratio (FLC-r), selected prognostic laboratory parameters i.e. Hb, platelets, albumin, β2-microglobulin (β2-M), Ca, lactate dehydrogenase (LDH), creatinine and the Durie-Salmon (D-S) and International Staging System (ISS), stages (1-3) for MM. Hevylite assays were done on the sera of 132 MM patients at the time of diagnosis (IgG 94, IgA 38). HLC-r was calculated in the case of i-HLC-κ from the i-HLC-κ/u-HLC-λ ratio and for i-HLC-λ from the i-HLC-λ/u-HLC-κ ratio. D-S and ISS stages were evenly distributed. Md IgG-κ HLC-r was 64.8 (2.7-2222) and of IgG-λ HLC-r 49.6 (0.7-465.1), in the case of IgA-κ, Md HLC-r was 408.9 (3.4-3966) and for IgA-λ HLC-r the Md was 180.0 (0.1-3110). Normal levels of HLC pairs and HLC-r did not always rule out the diagnosis of MM. HLC-r correlated with FLC-r in IgG (r = 0.244, P = 0.018), but not in the IgA type. For IgG, HLC-r values were significantly different in patients with abnormal vs normal levels of Hb (P < 0.0001), albumin (P < 0.043), β2-M (P < 0.0001) and creatinine (P = 0.034) but not thrombocyte count, Ca or LDH. For the IgA isotype, we found a significant difference in HLC-r values only for thrombocyte count (P = 0.026) and β2-M (P = 0.016) but not for Hb, albumin, Ca, LDH or creatinine. For the IgG isotype there was a significant relationship of HLC-r index to stages 1-3 (P = 0.038) and substage A vs B (P = 0.048) according to D-S, and with high significance to stages 1-3 according to ISS (P = 0.005) and between stages 1 vs 3 (P = 0.001). For the IgA isotype, we found significant differences in HLC-r only between stages 1-3 (P = 0.025) according to D-S but not in the case of ISS. There were no significant correlations between i-HLC Ig levels and D-S or ISS stages in both IgG-κ and λ and IgA-κ and λ. Exceptions were significant differences for stages 1 vs 3 (P = 0.012) and 2 vs 3 (P = 0.017) for the IgG-λ isotype. There were no correlations of the HLC-r and u-HLC levels for either D-S or ISS stratifications in all HLC isotypes. We found a significant positive contribution of HLC-r using the i-HLC/u-HLC ratio even in the case of i-HLC-λ i.e. i-HLC-λ/u-HLC-κ. Variable results for the relationship of important laboratory parameters and D-S and ISS stratifications (stage 1-3) to HLC-r values in IgG and IgA isotypes make separate interpretation of the Hevylite method results necessary in clinical practice.

Summary Background: The aim of the study was the comparison of two novel stratification models in multiple myeloma (MM), ie. according to Avet-Loiseau (A-L) and according to Ludwig (L), based on the HLC-r index (ratio of serum levels of involved- HLC/ uninvolved-HLC, ie. HLC-κ/ HLC-_λ assessed using ie. nephelometric/turbidimetric technique using specific polyclonal antibodies on a...

N?pln? p?edlo?en?ho sd?len? je klasifikace amyloid?z, p?edstaven? klinick?ch projev?, p?ehled vy?et?ovac?ch metod a ??eln? diagnostick? algoritmus syst?mov? AL amyloid?zy. Hlub?? pozornost je v?nov?na recentn?m vy?et?ovac?m technik?m a jejich ... N?pln? p?edlo?en?ho sd?len? je klasifikace amyloid?z, p?edstaven? klinick?ch projev?, p?ehled vy?et?ovac?ch metod a ??eln? diagnostick? algoritmus syst?mov? AL amyloid?zy. Hlub?? pozornost je v?nov?na recentn?m vy?et?ovac?m technik?m a jejich ...

Cardiac involvement is a dominant prognostic factor in AL amyloidosis patients. A detailed assessment of the presence and degree of cardiac involvement utilizes an array of noninvasive investigation methods, particularly echocardiography and MRI; laboratory parameters include troponins and natriuretic peptides. Cardiac involvement detection aside, cardiac bio-markers are used as a relatively strong stratification and prognostic factor. The presentation of cardiac bio-markers assay applications in AL amyloidosis patients at an individual treatment center. The monitored patient set consisted of 22 patients with histologically confirmed AL amyloidosis, of whom 18 met the criteria for cardiac involvement. Levels of cardiac bio-markers troponin T (TnT) and Nterminal probrain natriuretic peptide (NT ProBNP) were determined in all patients. Risk stratification of the patients utilized the Mayo staging system which is based on both bio-markers assays; Log Rank Test was applied to survival evaluation. Median survival of patients with cardiac involvement stigmata was 10 months vs 60 months survival of patients without signs of cardiac involvement (p = 0.133). Of the 4 patients without cardiac involvement, 1 has shown positive levels of TnT and 2 positive levels of NT ProBNP. All cardiac involvement patients exhibited abnormal levels of NT ProBNP (median 4,752 ng/ l; 415.7- 35,000) as well as positive levels of TnT (median 0.0815 μg/ l; 0.02- 0.986). The application of the Mayo stratification system to the set had determined 2 patients at stage I, 5 patients at stage II and 15 patients at stage III. The median survival of the Mayo I + II group vs the Mayo III group was 60 vs 6 months (p = 0.015), revealing extremely limited survival of stage III patients. Assessment of TnT and NT ProBNP levels relative to treatment response shows that the degree of decrease in both markers depends on maximum treatment response - respectively the attainment of a complete hematological remission. The results, although obtained from a limited set of patients, confirm a definitive benefit of the application of cardiac bio-markers assay in the diagnostic and therapeutic algorithm of AL amyloidosis patients. The Mayo stratification system utilizing the cardiac indicator values represents a robust tool for risk stratification of AL amyloidosis patients.

N?pln? sd?len? je pod?n? aktu?ln? informace o v?znamu vy?et?ov?n? ukazatel? kostn?ho metabolismu u mnoho?etn?ho myelomu (MM). Hlub?? pozornost je v?nov?na obecn?mu postaven? marker? kostn? remodelace v hodnocen? myelomov? kostn? nemoci (MKN) a... N?pln? sd?len? je pod?n? aktu?ln? informace o v?znamu vy?et?ov?n? ukazatel? kostn?ho metabolismu u mnoho?etn?ho myelomu (MM). Hlub?? pozornost je v?nov?na obecn?mu postaven? marker? kostn? remodelace v hodnocen? myelomov? kostn? nemoci (MKN) a...

Until 2011, the gold standard of treatment for patients with AL amyloidosis was the combination of alkylating cytostatics (melphalan or cyclophosphamide) and dexamethasone. For a selected group of patients under 65 years of age with only moderate damage to their body caused by amyloid and with good cardiac function (EF> 40%), high-dose chemotherapy with autologous hematopoietic cell transplantation seems to be optimal. Patients with AL amyloidosis and low bone marrow plasma cell count generally undergo the harvest of hematopoietic cells from peripheral blood, followed by high-dose chemotherapy immediately after they are diagnosed. In contrast to multiple myeloma, high-dose chemotherapy is not preceded by several months of conventional treatment. The year 2012 witnessed a release of reports about extensive experience with new drugs that were used in Phase I and Phase II clinical trials, and in isolated cases also in Phase III, for the treatment of patients with AL amyloidosis. Based on these studies it can be concluded that among the new available drugs (bortezomib, thalidomide and lenalidomide) bortezomib is the drug with the greatest curative effect in patients with AL amyloidosis; it achieved 24-37% of complete remissions in monotherapy. The greatest number of treatment responses was reported during the treatment that combined bortezomib, alkylating cytostatics and dexamethasone. This treatment showed significantly more treatment responses during the first-line drug therapy than during therapies that followed. Clinical trials with lenalidomide combined with other drugs saw a lower number of treatment responses than the number described in treatment with bortezomib combined with other drugs. That is the reason why lenalidomide combinations are not considered the optimal first-line therapy, with the exception of AL amyloidosis with bortezomib contraindication (severe neuropathy caused by AL amyloidosis). It was confirmed that lenalidomide combined with other drugs could cause remission in patients whose disease was resistant to the initial bortezomib therapy. Lenalidomide (or alternatively also thalidomide) can therefore be used as second-line therapy if bortezomib therapy proves unsuccessful, with the possibility of achieving a complete remission. The increase in the number of complete remissions brought about by bortezomib therapies in patients with AL amyloidosis poses a question about which treatment should be used for younger patients with only moderate damage to their body, i.e. high-dose chemotherapy with autologous hematopoietic cell transplantation or combined treatment with bortezomib. Additional comparative studies are required to be able to answer that question and determine which of the aforesaid therapy modalities is optimal. A question still remains whether the increase in the number of complete remissions due to bortezomib will also bring about longer survival comparable to the results of high-dose chemotherapy treatment with autologous hematopoietic cell transplantation.

N?pln? sd?len? je, na pozad? rozboru diagnostiky a l??by vlastn?ch t?? nemocn?ch, pod?n? sou?asn?ch poznatk? o pom?rn? vz?cn?m a v b?n? klinick? praxi opom?jen?m onemocn?n?, vyzna?uj?c?m se depozic? lehk?ho ?et?zce imunoglobulinu v tk?n?ch ?i... N?pln? sd?len? je, na pozad? rozboru diagnostiky a l??by vlastn?ch t?? nemocn?ch, pod?n? sou?asn?ch poznatk? o pom?rn? vz?cn?m a v b?n? klinick? praxi opom?jen?m onemocn?n?, vyzna?uj?c?m se depozic? lehk?ho ?et?zce imunoglobulinu v tk?n?ch ?i...