Rituximab followed by cladribine in the treatment of heavily pretreated patients with indolent lymphoid malignancies

The purpose of this study was to determine the efficacy and toxicity of combined therapy consisting of rituximab (RIT), an anti-CD20 monoclonal antibody, and cladribine (2-chlorodeoxyadenosine, 2-CdA) (RC regimen) in patients with refractory or relapsed indolent lymphoproliferative disorders. Twenty six CD20 antigen positive patients, 15 with B-cell chronic lymphocytic leukemia (B-CLL) and 11 with low grade non-Hodgin's lymphoma (LG-NHL) were enrolled to the study. Fourteen patients (53.8%) had refractory disease, the other 12 (46.2%) were recurrent after prior chemotherapy. RC regimen consisted of RIT at a dose of 375 mg/m² in 6 h infusion on day 1 and 2-CdA at a dose of 0.12 mg/kg, in 2 h infusion, given on days 2 - 6. The RC courses were repeated at 4 week intervals or longer if severe myelosuppression occurred. Seventy eight cycles of RC with median of 3 cycles per patient were administered (range 1 - 5 cycles). Four patients (15.4%) (95% CI 1.5 - 29.3% ), 1 with B-CLL and 3 with LG-NHL, achieved a complete response (CR). Fourteen patients (53,8%) (95%CI 34.6 - 72.9%), including 10 with B-CLL and 4 with LG-NHL, had a partial response (PR). Overall response rate (OR) was 69.2% (95%CI 51.4 - 86.9 %) in the whole group, from 63.6% (95% CI 35.2 - 92.0%) in LG-NHL to 73.3% (95%CI 50.1 - 95.7%) in B-CLL patients. Twelve of 18 patients with CR/PR are still in remission, with the median follow up 10 (7 - 28 months). The median failure-free survival (FFS) of responders was 6.5 months. Hypersensitivity to RIT was the major toxicity of RC regimen, and occurred in 9 patients (34.6%), mostly only during the first infusion of RIT. Severe neutropenia (grade III) was seen in 3 patients (11.5%). Anemia and thrombocytopenia associated with RC treatment were observed in 5 (19.2%) and 2 patients (7.7%), respectively. Four episodes (15.4%) of grade III - IV infections were observed. There was no treatment related mortality. During the follow-up six patients (23.1%) died from the disease progression. In conclusion, the combination of RIT and 2-CdA is an effective and well tolerated treatment, even for heavily pre-treated patients, and the results seem to be better than in patients previously treated in our institution with 2-CdA alone. This regimen can be considered as an alternative treatment of CD-20 positive indolent lymphoproliferative disorders.     

A Top-Down Approach and Thermal Characterization of Luminescent Hybrid BPA.DA-MMA@Ln2L3 Materials Based on Lanthanide(III) 1H-Pyrazole-3,5-Dicarboxylates

In this study, novel hybrid materials exhibiting luminescent properties were prepared and characterized. A top-down approach obtained a series of polymeric materials with incorporated different amounts (0.1; 0.2; 0.5; 1, and 2 wt.%) of dopants, i.e., europium(III) and terbium(III) 1H-pyrazole-3,5-dicarboxylates, as luminescent sources. Methyl methacrylate and bisphenol A diacrylate monomers were applied for matrix formation. The resulting materials were characterized using Fourier transform infrared spectroscopy (FTIR) and thermal analysis methods (TG-DTG-DSC, TG-FTIR) in air and nitrogen atmosphere, as well as by luminescence spectroscopy. The homogeneity of the resulting materials was investigated by means of optical microscopy. All obtained materials exhibited good thermal stability in both oxidizing and inert atmospheres. The addition of lanthanide(III) complexes slightly changed the thermal decomposition pathways. The main volatile products of materials pyrolysis are carbon oxides, water, methyl methacrylic acid and its derivatives, bisphenol A, 4-propylphenol, and methane. The luminescence properties of the lanthanide complexes and the prepared hybrid materials were investigated in detail.     

Serum inflammatory markers in the diagnosis and assessment of Crohn’s disease activity

IntroductionThe aim of our study was to evaluate the diagnostic characteristics of selected inflammatory markers and the results of multiplication of their concentrations in the diagnosis and assessment of Crohn’s disease (CD) activity.MethodsWe studied 49 patients with CD and 31 healthy controls. The CD patients were assigned to subgroups with active and inactive disease based on the Crohn’s Disease Activity Index score. Serum interleukins and C-reactive protein (CRP) were measured using immunoassays.ResultsSerum CRP and interleukins: IL-6, IL-17A, IL-23 were significantly higher in the CD group than in controls, with the best diagnostic performance for IL-23. Only serum IL-6 and CRP were significantly higher in active than in inactive disease, with the better performance of CRP. Multiplication results did not perform better than individual multipliers.ConclusionsSerum CRP may be useful in the assessment of CD activity and there is a need for introduction of IL-23 for the CD diagnosis.     

Liver injury in the era of COVID-19

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has undoubtedly revolutionized the whole globe and given a new point of view on respiratory tract infections. Nevertheless, coronavirus disease 2019 (COVID-19) cannot be perceived as a disease limited only to pneumonia with diverse severity. More and more reports have demonstrated a wide range of possible systemic symptoms, including hepatic complications. Liver injury has been observed in a significant proportion of patients, especially in those with a severe or critical illness. COVID-19 might provoke a deterioration of liver function in patients with already diagnosed chronic liver diseases and without pre-existing liver disorders. The deterioration of liver function worsens the prognosis, increases the risk of a severe course of SARS-CoV-2 infection and prolongs the hospital stay. In general, patients who develop liver dysfunction in COVID-19 are mainly males, elderly people, and those with higher body mass index. The underlying mechanisms for hepatic failure in patients infected with SARS-CoV-2 are still unclear, nevertheless liver damage appears to be directly connected with virus-induced cytopathic effects. A liver injury observed during hospitalization might be simultaneously caused by the use of potentially hepatotoxic drugs, mainly antiviral agents. This minireview focuses on a possible relationship between COVID-19 and the liver, potential molecular mechanisms of liver damage, the characteristics of liver injury and suggested factors predisposing to hepatic manifestations in COVID-19 patients.     

Root and canal morphology of the maxillary second premolars as indicated by cone beam computed tomography

The aim was to evaluate the morphology of maxillary second premolars. The root canal configurations were classified according to Vertucci and a new system by Ahmed et al. based on CBCT images. In addition, the number of roots and the level where they bifurcated were identified, and morphological measurements were performed based on anatomical landmarks. Single-rooted forms were most common. Bifurcation occurred most often in the middle part of the root. The most common canal configuration was type I according to Vertucci and code ¹SP¹ according to the new classification. The measurements showing the results were as follows (mm): palatal cusp/buccal cusp/the lowest point of the occlusal surface to pulp chamber ceiling 6.18/6.54/4.77; the ceiling of the pulp chamber was found at the CEJ in 92.28% of the specimens. The maxillary second premolars tended to be single-rooted and with one root canal.