BACKGROUND: Auer rods (AuRs) are prominent intracellular structures found almost exclusively in myeloid cell malignancies, such as acute myeloid leukemia (AML), chronic and juvenile myelomonocytic leukemia and myelodysplastic syndrome. Extremely rare AuRs have been reported in patients with acute lymphoblastic leukemia (ALL) or among ambiguous lineage leukemia patients with a dominantly lymphoblastic immunophenotype. PROCEDURE: We report diagnostic and follow-up data of an international cohort of 11 children suffering from leukemias with AuRs and with significant presence of T and myeloid markers, majority of whom categorized as early T-cell precursor (ETP, n = 7); or T-ALL (ETP status unknown, n = 2), ALAL (acute leukemia of ambiguous lineage, n = 1), and AML reclassified from ALAL (n = 1). We described other diagnostic details and treatment types and responses. Moreover, we summarize previously published data. RESULTS: Among the four patients who started and remained on ALL-type therapy, all were in the first complete remission, whereas both patients who started and remained on AML-type therapy relapsed and died. Of the patients who followed either a combined ALL/AML protocol (Interfant 06) or who switched from one of the two types of therapy to the other, one patient died, and the remaining four were in first complete remission at the most recent follow-up. We also searched for similar cases in the literature and found only three additional children with nonmyeloid leukemia and AuRs and 10 adults with this type of leukemia. CONCLUSIONS: Briefly, ALL- or combined ALL/AML-type therapy may be effective for treating AuR-positive leukemia patients with a lymphoid immunophenotype.

• MeSH
• akutní lymfatická leukemie patologie   terapie   imunologie   MeSH
• akutní myeloidní leukemie patologie   terapie   imunologie   MeSH
• dítě MeSH
• imunofenotypizace * MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• následné studie MeSH
• předškolní dítě MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Up to 65% of patients with chronic myeloid leukemia (CML) who are treated with imatinib do not achieve sustained deep molecular response, which is required to attempt treatment-free remission. Asciminib is the only approved BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket. This unique mechanism of action allows asciminib to be combined with adenosine triphosphate-competitive tyrosine kinase inhibitors to prevent resistance and enhance efficacy. The phase II ASC4MORE trial investigated the strategy of adding asciminib to imatinib in patients who have not achieved deep molecular response with imatinib. METHODS: In ASC4MORE, 84 patients with CML in chronic phase not achieving deep molecular response after ≥ 1 year of imatinib therapy were randomized to asciminib 40 or 60 mg once daily (QD) add-on to imatinib 400 mg QD, continued imatinib 400 mg QD, or switch to nilotinib 300 mg twice daily. RESULTS: More patients in the asciminib 40- and 60-mg QD add-on arms (19.0% and 28.6%, respectively) achieved MR4.5 (BCR::ABL1 ≤ 0.0032% on the International Scale) at week 48 (primary endpoint) than patients in the continued imatinib (0.0%) and switch to nilotinib (4.8%) arms. Fewer patients discontinued asciminib 40- and 60-mg QD add-on treatment (14.3% and 23.8%, respectively) than imatinib (76.2%, including crossover patients) and nilotinib (47.6%). Asciminib add-on was tolerable, with rates of AEs and AEs leading to discontinuation less than those with nilotinib, although higher than those with continued imatinib (as expected in these patients who had already been tolerating imatinib for ≥ 1 year). No new or worsening safety signals were observed with asciminib add-on vs the known asciminib monotherapy safety profile. CONCLUSIONS: Overall, these results support asciminib add-on as a treatment strategy to help patients with CML in chronic phase stay on therapy to safely achieve rapid and deep response, although further investigation is needed before this strategy is incorporated into clinical practice. TRIAL REGISTRATION: NCT03578367.

• MeSH
• bcr-abl fúzové proteiny antagonisté a inhibitory   MeSH
• chronická myeloidní leukemie * farmakoterapie   MeSH
• dospělí MeSH
• imatinib mesylát * terapeutické užití   MeSH
• inhibitory proteinkinas terapeutické užití   aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• niacinamid analogy a deriváty   MeSH
• protokoly antitumorózní kombinované chemoterapie * terapeutické užití   MeSH
• pyrazoly MeSH
• pyrimidiny terapeutické užití   aplikace a dávkování   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

OBJECTIVE: Evidence is lacking to guide the management of infective native aortic aneurysm (INAA). The aim of this study was to establish expert consensus on surgical and antimicrobial treatment and follow up, and to define when an INAA is considered cured. METHODS: Delphi methodology was used. The principal investigators invited 47 international experts (specialists in infectious diseases, radiology, nuclear medicine, and vascular and cardiothoracic surgery) via email. Four Delphi rounds were performed, three weeks each, using an online questionnaire with initially 28 statements. The panellists rated the statements on a five point Likert scale. Comments on statements were analysed, statements were revised and added or deleted, and the results were presented in the iterative rounds. Consensus was defined as ≥ 75% of the panel rating a statement as strongly agree or agree on the Likert scale, and consensus on the final assessment was defined as Cronbach's alpha > 0.80. RESULTS: All 49 panellists completed all four rounds, resulting in 100% participation. One statement was added based on the results and comments of the panel, resulting in 29 final statements: three on need for consensus, 20 on treatment, five on follow up, and one on definition of cure. All 29 statements reached agreement of ≥ 86%. Cronbach's alpha increased for each consecutive round; round 1, 0.85; round 2, 0.90; round 3, 0.91; and round 4, 0.94. Thus, consensus was reached for all statements. CONCLUSION: INAAs are rare, and high level evidence to guide optimal management is lacking. This consensus document was established with the aim of helping clinicians manage these challenging patients, as a supplement to current guidelines. The presented consensus will need future amendments in accordance with newly acquired knowledge.

• MeSH
• aortální aneurysma * MeSH
• delfská metoda MeSH
• konsensus MeSH
• lidé MeSH
• následné studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: A higher risk of secondary brain tumor, carotid stenosis, and stroke has been reported after conventional sella irradiation for pituitary neuroendocrine tumors (PitNET). Stereotactic radiosurgery (SRS), which is a more focused approach, is now increasingly used instead. The aim was to assess the risk of secondary brain tumor, carotid stenosis/occlusion, and stroke after SRS. METHODS: In this multicentric retrospective study, 2254 patients with PitNET were studied, 1377 in the exposed group, and 877 in the control group. RESULTS: There were 9840.1 patient-years at risk for the SRS and 5266.5 for the control group. The 15-year cumulative probability of secondary intracranial tumor was 2.3% (95% CI: 0.5%, 4.1%) for SRS and 3.7% (95% CI: 0%, 8.7%) for the control group (P = .6), with an incidence rate of 1.32 per 1000 and 0.95 per 1000, respectively. SRS was not associated with an increased risk of tumorigenesis when stratified by age (HR: 1.59 [95% CI: 0.57, 4.47], Pp = .38). The 15-year probability of new carotid stenosis/occlusion was 0.9% (95% CI: 0.2, 1.6) in the SRS and 2% (95% CI: 0, 4.4) in the control group (P = .8). The 15-year probability of stroke was 2.6% (95% CI: 0.6%, 4.6%) in the SRS and 11.1% (95% CI: 6%, 15.9%) in the control group (P < .001). In Cox multivariate analysis stratified by age, SRS (HR 1.85 [95% CI:0.64, 5.35], P = .26) was not associated with risk of new stroke. CONCLUSIONS: No increased risk of long-term secondary brain tumor, new stenosis or occlusion, and stroke was demonstrated in the SRS group compared to the control in this study with imaging surveillance.

• MeSH
• cévní mozková příhoda * etiologie   epidemiologie   MeSH
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory hypofýzy * epidemiologie   MeSH
• nádory mozku epidemiologie   etiologie   MeSH
• následné studie MeSH
• prognóza MeSH
• radiochirurgie * škodlivé účinky   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• sekundární malignity etiologie   epidemiologie   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stenóza arteria carotis * etiologie   epidemiologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND AND AIMS: The question of when and how to treat truly asymptomatic patients with severe aortic stenosis (AS) and normal left ventricular (LV) systolic function is still subject to debate and ongoing research. Here, the results of extended follow-up of the AVATAR trial are reported (NCT02436655, ClinicalTrials.gov). METHODS: The AVATAR trial randomly assigned patients with severe, asymptomatic AS and LV ejection fraction ≥ 50% to undergo either early surgical aortic valve replacement (AVR) or conservative treatment with watchful waiting strategy. All patients had negative exercise stress testing. The primary hypothesis was that early AVR will reduce a primary composite endpoint comprising all-cause death, acute myocardial infarction, stroke, or unplanned hospitalization for heart failure (HF), as compared with conservative treatment strategy. RESULTS: A total of 157 low-risk patients (mean age 67 years, 57% men, mean Society of Thoracic Surgeons score 1.7%) were randomly allocated to either the early AVR group (n = 78) or the conservative treatment group (n = 79). In an intention-to-treat analysis, after a median follow-up of 63 months, the primary composite endpoint outcome event occurred in 18/78 patients (23.1%) in the early surgery group and in 37/79 patients (46.8%) in the conservative treatment group [hazard ratio (HR) early surgery vs. conservative treatment 0.42; 95% confidence interval (CI) 0.24-0.73, P = .002]. The Kaplan-Meier estimates for individual endpoints of all-cause death and HF hospitalization were significantly lower in the early surgery compared with the conservative group (HR 0.44; 95% CI 0.23-0.85, P = .012, for all-cause death and HR 0.21; 95% CI 0.06-0.73, P = .007, for HF hospitalizations). CONCLUSIONS: The extended follow-up of the AVATAR trial demonstrates better clinical outcomes with early surgical AVR in truly asymptomatic patients with severe AS and normal LV ejection fraction compared with patients treated with conservative management on watchful waiting.

• MeSH
• aortální chlopeň chirurgie   MeSH
• aortální stenóza * chirurgie   mortalita   terapie   MeSH
• asymptomatické nemoci terapie   MeSH
• avatar MeSH
• cévní mozková příhoda MeSH
• chirurgická náhrada chlopně * metody   MeSH
• hospitalizace statistika a číselné údaje   MeSH
• konzervativní terapie * metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• pozorné vyčkávání MeSH
• senioři MeSH
• tepový objem fyziologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

OBJECTIVE: Sparse data exist on the impact of upper urinary tract (UUT) decompression on the risk of UUT recurrence in patients with bladder cancer (BCa). This study aims to evaluate whether Double J stenting (DJS) can increase the risk of UUT recurrence compared to percutaneous nephrostomy (PCN) placement. MATERIALS AND METHODS: We retrospectively analyzed data from 1550 patients with cTa-T3NanyM0 BCa who underwent radical cystectomy (RC) between at 12 tertiary care centers (1990-2020). Patients with complete follow-up, no prior history of UUT cancer, and who required UUT decompression for preoperative hydronephrosis were selected. Hydronephrosis grade was defined according to established scoring systems. UUT recurrence was diagnosed through imaging, urinary cytology, and confirmed by selective cytology and ureteroscopy when possible. Propensity scores were computed to determine overlap weights and balance groups. Kaplan-Meier analyses estimated UUT recurrence-free survival (RFS), cancer-specific (CSS), and overall survival (OS) before and after weighting. Cox regression analyses before and after weighting were fitted to predict UUT recurrence. RESULTS: Of 524 included patients, 132 (25%) and 392 (75%) patients were managed with DJS and PCN placement, respectively. Patients who received PCN had higher grade (≥ 3) of obstruction (34% vs. 14%) and pT3-4 tumors (70% vs. 36%) than patients with DJS. During a median follow-up of 19 months, 2-years UUT-RFS did not differ between groups (95% for PCN vs 92% for DJS, weighted HR 1.41, 95% CI, 0.55-3.59). There was no difference in 2-years weighted CSS (74% vs. 74%) and OS (67% vs 69%). Main limitations were the short follow-up and inclusion of patients uniquely undergoing RC. CONCLUSIONS: These results suggest that ureteral DJS does not increase the risk of developing UUT recurrence in BCa patients with hydronephrosis requiring UUT decompression. However, UUT recurrence was rare, and associations were weak, with findings susceptible to bias. Randomized trials are needed to validate these results.

• MeSH
• cystektomie MeSH
• hydronefróza etiologie   MeSH
• karcinom z přechodných buněk chirurgie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory močového měchýře * chirurgie   patologie   MeSH
• nádory močovodu chirurgie   patologie   MeSH
• následné studie MeSH
• perkutánní nefrostomie MeSH
• retrospektivní studie MeSH
• sekundární malignity chirurgie   patologie   MeSH
• senioři MeSH
• stenty * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: We recently described magnetic resonance imaging (MRI) features of children with transverse myelitis (TM) at first event with important and unique differences depending on the underlying disease entity. OBJECTIVE: To study the resolution of lesions over time in children with TM due to MOG-antibody associated disorders (MOGAD), multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) or double seronegative TM. PATIENTS AND METHODS: In this prospective study, 78 children from 29 different medical centres with TM as part of MOGAD (n = 34), MS (n = 20), NMOSD (n = 5) and in double seronegative children (n = 19) were included. A grading system consisting of 4 grades (grade 0 = complete resolution; grade 3 = no resolution at all) was used to compare the degree of lesion resolution over time in the different disease entities. Time to lesion resolution was evaluated by Kaplan-Meier statistics and log-rank test. RESULTS: Significant differences of the interval between first MRI until resolution of lesions were observed between the four disease entities. The most rapid and complete resolution was seen in MOGAD, followed by double seronegative, MS and NMOSD. Median periods until total resolution (grade 0) were 191 days (MOGAD), 750 days (double seronegative), 1117 days (MS), while none of the patients with NMOSD reached a complete resolution during the observation period. The better prognosis of MOGAD compared to MS was independent of sex, age, oligoclonal bands and cell count in the multivariate Cox analysis (P < 0.001). CONCLUSION: Children with TM and antibodies to MOG show a faster resolution of radiological lesions compared to children with MS and NMOSD.

• MeSH
• autoprotilátky krev   MeSH
• dítě MeSH
• glykoprotein v myelinu oligodendrocytů imunologie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mícha diagnostické zobrazování   patologie   MeSH
• mladiství MeSH
• následné studie MeSH
• neuromyelitis optica * diagnostické zobrazování   MeSH
• předškolní dítě MeSH
• prospektivní studie MeSH
• roztroušená skleróza * diagnostické zobrazování   patologie   MeSH
• transverzální myelitida * diagnostické zobrazování   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND AND OBJECTIVE: Persistent prostatic specific antigen (PSA) represents a poor prognostic factor for recurrence after radical prostatectomy (RP). However, the impact of persistent PSA on oncologic outcomes in patients undergoing salvage RP is unknown. To investigate the impact of persistent PSA after salvage RP on long-term oncologic outcomes. MATERIAL AND METHODS: Patients who underwent salvage RP for recurrent prostate cancer between 2000 and 2021 were identified from twelve high-volume centers. Only patients with available PSA after salvage RP were included. Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of persistent PSA on biochemical recurrence (BCR), metastasis and any death after salvage RP. Persistent PSA was defined as a PSA-value ≥ 0.1 ng/ml, at first PSA-measurement after salvage RP. RESULTS: Overall, 580 patients were identified. Of those, 42% (n = 242) harbored persistent PSA. Median follow-up after salvage RP was 38 months, median time to salvage RP was 64 months and median time to first PSA after salvage RP was 2.2 months. At 84 months after salvage RP, BCR-free, metastasis-free, and overall survival was 6.6 vs. 59%, 71 vs. 88% and 77 vs. 94% for patients with persistent vs. undetectable PSA after salvage RP (all p < 0.01). In multivariable Cox models persistent PSA was an independent predictor for BCR (HR: 5.47, p < 0.001) and death (HR: 3.07, p < 0.01). CONCLUSION: Persistent PSA is common after salvage RP and represents an independent predictor for worse oncologic outcomes. Patients undergoing salvage RP should be closely monitored after surgery to identify those with persistent PSA.

• MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru * patologie   chirurgie   krev   MeSH
• nádorové biomarkery krev   MeSH
• nádory prostaty * chirurgie   patologie   krev   mortalita   MeSH
• následné studie MeSH
• prognóza MeSH
• prostatektomie * metody   MeSH
• prostatický specifický antigen * krev   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• záchranná terapie * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

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.

• 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

BACKGROUND: Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare childhood cancer predisposition syndrome associated with a broad spectrum of malignancies, including non-Hodgkin lymphomas (NHL). Most patients die due to cancer before the age of 20 years. Limited data exist on CMMRD-associated lymphomas and their outcome. METHODS: We conducted a retrospective study including all CMMRD-associated NHL patients registered before 2020 in the European and North American databases or reported by members of the European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL). Events considered to define event-free survival included relapse/progression, second malignancy (SML), or death, whichever occurred first. FINDINGS: The analysis included 74 patients, with 20 having multiple metachronous NHL. The median age at diagnosis was 9.4 years. Previous malignancies were reported in 36% of the patients, café au lait spots in 96%, and consanguinity in 54%. The initial lymphoma subtypes were 53 T-cell lymphoblastic lymphomas (T-LBL), four B-lymphoblastic lymphomas, and 17 mature B-cell non-Hodgkin lymphoma (B-NHL). All patients were treated with curative intent, with current chemotherapy regimens adapted to their subtype. The median follow-up was 8.7 years. After the first lymphoma, the 5-year event-free and overall survival rates were, respectively, 23.5% [95% confidence interval (CI): 14.9-35.1] and 61.5% [95% CI: 49.6-72.1]. The 5-year cumulative risk of progression/relapse, SML or death as a first event was 20.8%, 52.9%, and 2.7%. INTERPRETATION: Standard treatments for sporadic NHL are effective in most CMMRD-associated NHL cases, but multiple malignancies, including lymphomas, impair prognosis. Future strategies should evaluate the potential of less genotoxic therapies, including immunotherapy, in preventing SMLs while maintaining effective control of NHL.

• MeSH
• dědičné nádorové syndromy genetika   mortalita   MeSH
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• kolorektální nádory MeSH
• lidé MeSH
• míra přežití MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory mozku MeSH
• následné studie MeSH
• nehodgkinský lymfom * mortalita   genetika   epidemiologie   MeSH
• předškolní dítě MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH