ZZN Pelhřimov (Czechia)

Until recently, a combination of anti-CD20 antibody plus less intensive chemotherapy was a standard of care in elderly population with previously untreated chronic lymphocytic leukemia (CLL). The aim of this observational study was to retrospectively assess efficacy and safety of obinutuzumab + chlorambucil (G-Clb), rituximab + chlorambucil (R-Clb), and bendamustine + rituximab (BR) given as the frontline therapy within routine practice. The final analyzed dataset included 398 consecutive CLL patients from 10 hematology centers cooperating within the Czech CLL Study Group: 63 treated with G-Clb, 78 with R-Clb, and 257 with BR. There were no significant differences in prognostic and predictive markers among the groups. On the contrary, median age at the start of therapy and cumulative illness rating scale (CIRS) score was significantly higher in R-Clb group. Obinutuzumab plus chlorambucil regimen was preferably offered to elderly patients (compared to BR) with less severe comorbidities and lower CIRS score (compared to R-Clb). A time period when a treatment was indicated had also a strong impact on the choice of the regimen. The overall response rate reached 76% (30% complete remissions, CRs) in G-Clb, 75% (22% CRs) in R-Clb, and 85% (47% CRs) in BR group. Median event-free survival was 49.0 months for G-Clb, 20.3 months for R-Clb, and 37.0 months for BR group. Neutropenia grade ≥ 3 developed in 43% of G-Clb, 31% of R-Clb and in 49% of BR patients, grade ≥ 3 infections were recorded in 17% of G-Clb, 6.4% of R-Clb, and 17% of BR patients. In conclusion, real-world therapeutic activity of G-Clb appears to be at least comparable to prospective clinical trial data. R-Clb yields relatively good results in very old and severely comorbid patients.

Objectives: We conducted an adjusted comparison of progression-free survival (PFS) and overall survival (OS) for daratumumab monotherapy versus standard of care, as observed in a real-world historical cohort of heavily pretreated multiple myeloma patients from Czech Republic.Methods: Using longitudinal chart data from the Registry of Monoclonal Gammopathies (RMG) of the Czech Myeloma Group, patient-level data from the RMG was pooled with pivotal daratumumab monotherapy studies (GEN501 and SIRIUS; 16 mg/kg).Results: From the RMG database, we identified 972 treatment lines in 463 patients previously treated with both a proteasome inhibitor and an immunomodulatory drug. Treatment initiation dates for RMG patients were between March 2006 and March 2015. The most frequently used treatment regimens were lenalidomide-based regimens (33.4%), chemotherapy (18.1%), bortezomib-based regimens (13.6%), thalidomide-based regimens (8.0%), and bortezomib plus thalidomide (5.3%). Few patients were treated with carfilzomib-based regimens (2.5%) and pomalidomide-based regimens (2.4%). Median observed PFS for daratumumab and the RMG cohort was 4.0 and 5.8 months (unadjusted hazard ratio [HR], 1.14; 95% confidence interval [CI], 0.94–1.39), respectively, and unadjusted median OS was 20.1 and 11.9 months (unadjusted HR, 0.61; 95% CI, 0.48–0.78), respectively. Statistical adjustments for differences in baseline characteristics were made using patient-level data. The adjusted HRs (95% CI) for PFS and OS for daratumumab versus the RMG cohort were 0.79 (0.56–1.12; p = .192) and 0.33 (0.21–0.52; p < .001), respectively.Conclusions: Adjusted comparisons between trial data and historical cohorts can provide useful insights to clinicians and reimbursement decision makers on relative treatment efficacies in the absence of head-to-head comparison studies for daratumumab monotherapy.

The study was aimed at the clinical and biomechanical analyses of the sliding hip screw breakage with the use of finite element method. We have identified two patients with the sliding screw breakage. In the first patient, the biomechanical analysis revealed the reduced stress values σHMH not exceeding the yield limit or strength limit of the implant. The yield limit was exceeded in second one. Clinical and biomechanical analyses have demonstrated that adherence to technical requirements of the appropriate osteosynthesis implementation is the principal condition of timely healing since it prevents the material failure.

Hybrid pulmonary imaging in the present day has seen a fusion of various uses of CT scans, including angiography (CTAG), diagnostic CT, low dose CT (LDCT), and perfusion or ventilation scintigraphy in tomographic or planar imaging. Determining the most effective individualized test for the complete diagnostics of patients with pulmonary symptoms for various groups of patients is a major issue. The aim of the present study was to assess the effectiveness of the implementation of hybrid imaging in current methods of nuclear medicine in differential diagnostics of pulmonary embolism (PE). 326 patients were examined for symptomatology of PE. Patients were initially examined with SPECT perfusion scintigraphy. SPECT finding without sub-segmental or segmental defects was considered unproven PE but the finding of more segments or sub-segments in various lung parts was considered nearly proven PE. In the case of unclear findings, LDCT was added and in the case of a higher suspicion of PE, a ventilation examination was applied. It was possible to determine 83% of patients with the occurrence or exclusion of PE only on the basis of the perfusion SPECT examination and an X-ray or LDCT. LDCT was determined with 26% of the patients. With 41% of them, the use of LDCT resulted in an alternative diagnosis, explaining perfusion abnormalities. The research proved that use of SPECT/LDCT for differential diagnosis of lung symptoms brings about improvement in the diagnosis of pulmonary embolism or the identification of other lung diseases when lung perfusion abnormalities are recorded.

Monoclonal gammopathy of undetermined significance (MGUS) is a benign condition with an approximate 1% annual risk of symptomatic plasma cell disorder development, mostly to multiple myeloma (MM). We performed genomewide screening of copy-number alterations (CNAs) in 90 MGUS and 33 MM patients using high-density DNA microarrays. We identified CNAs in a smaller proportion of MGUS (65.6%) than in MM (100.0%, P = 1.31 × 10-5 ) and showed median number of CNAs is lower in MGUS (3, range 0-22) than in MM (13, range 4-38, P = 1.82 × 10-10 ). In the MGUS cohort, the most frequent losses were located at 1p (5.6%), 6q (6.7%), 13q (30.0%), 14q (14.4%), 16q (8.9%), 21q (5.6%), and gains at 1q (23.3%), 2p (6.7%), 6p (13.3%), and Xq (7.8%). Hyperdiploidy was detected in 38.9% of MGUS cases, and the most frequent whole chromosome gains were 3 (25.6%), 5 (23.3%), 9 (37.8%), 15 (23.3%), and 19 (32.2%). We also identified CNAs such as 1p, 6q, 8p, 12p, 13q, 16q losses, 1q gain and hypodiploidy, which are potentially associated with an adverse prognosis in MGUS. In summary, we showed that MGUS is similar to MM in that it is a genetically heterogeneous disorder, but overall cytogenetic instability is lower than in MM, which confirms that genetic abnormalities play important role in monoclonal gammopathies.