Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma.

BACKGROUND: Belantamab mafodotin had single-agent activity in patients with relapsed or refractory multiple myeloma, a finding that supports further evaluation of the agent in combination with standard-care therapies. METHODS: In this phase 3, open-label, randomized trial, we evaluated belantamab mafodotin, bortezomib, and dexamethasone (BVd), as compared with daratumumab, bortezomib, and dexamethasone (DVd), in patients who had progression of multiple myeloma after at least one line of therapy. The primary end point was progression-free survival. Key secondary end points were overall survival, response duration, and minimal residual disease (MRD)-negative status. RESULTS: In total, 494 patients were randomly assigned to receive BVd (243 patients) or DVd (251 patients). At a median follow-up of 28.2 months (range, 0.1 to 40.0), median progression-free survival was 36.6 months (95% confidence interval [CI], 28.4 to not reached) in the BVd group and 13.4 months (95% CI, 11.1 to 17.5) in the DVd group (hazard ratio for disease progression or death, 0.41; 95% CI, 0.31 to 0.53; P<0.001). Overall survival at 18 months was 84% in the BVd group and 73% in the DVd group. An analysis of the restricted mean response duration favored BVd over DVd (P<0.001). A complete response or better plus MRD-negative status occurred in 25% of the patients in the BVd group and 10% of those in the DVd group. Grade 3 or higher adverse events occurred in 95% of the patients in the BVd group and 78% of those in the DVd group. Ocular events were more common in the BVd group than in the DVd group (79% vs. 29%); such events were managed with dose modifications, and events of worsening visual acuity mostly resolved. CONCLUSIONS: As compared with DVd therapy, BVd therapy conferred a significant benefit with respect to progression-free survival among patients who had relapsed or refractory multiple myeloma after at least one line of therapy. Most patients had grade 3 or higher adverse events. (Funded by GSK; DREAMM-7 ClinicalTrials.gov number, NCT04246047; EudraCT number, 2018-003993-29.).

Predicting chemotherapy toxicity in multiple myeloma: the prognostic value of pre-treatment serum cytokine levels of interleukin-6, interleukin-8, monocyte chemoattractant protein-1, and vascular endothelial growth factor.

Introduction: Multiple Myeloma (MM), a prevalent hematological malignancy, poses significant treatment challenges due to varied patient responses and toxicities to chemotherapy. This study investigates the predictive value of pretreatment serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF) for chemotherapy-induced toxicities in newly diagnosed MM patients. We hypothesized that these cytokines, pivotal in the tumor microenvironment, might correlate with the incidence and severity of treatment-related adverse events. Methods: We conducted a prospective observational study with 81 newly diagnosed MM patients, analyzing serum cytokine levels using the multiplex cytometric bead assay (CBA) flow cytometry method. The study used non-parametric and multivariate analysis to compare cytokine levels with treatment-induced toxicities, including lymphopenia, infections, polyneuropathy, and neutropenia. Results: Our findings revealed significant associations between cytokine levels and specific toxicities. IL-8 levels were lower in patients with lymphopenia (p=0.0454) and higher in patients with infections (p=0.0009) or polyneuropathy (p=0.0333). VEGF concentrations were notably lower in patients with neutropenia (p=0.0343). IL-8 demonstrated an 81% sensitivity (AUC=0.69; p=0.0015) in identifying infection risk. IL-8 was an independent predictor of lymphopenia (Odds Ratio [OR]=0.26; 95% Confidence Interval [CI]=0.07-0.78; p=0.0167) and infection (OR=4.76; 95% CI=0.07-0.62; p=0.0049). High VEGF levels correlated with a 4-fold increased risk of anemia (OR=4.13; p=0.0414). Conclusions: Pre-treatment concentrations of IL-8 and VEGF in serum can predict hematological complications, infections, and polyneuropathy in patients with newly diagnosed MM undergoing chemotherapy. They may serve as simple yet effective biomarkers for detecting infections, lymphopenia, neutropenia, and treatment-related polyneuropathy, aiding in the personalization of chemotherapy regimens and the mitigation of treatment-related risks.

Selected structures of middle ear relevant to cochlear implantation on the basis of computer tomography.

BACKGROUND: The primary objective of this study was to analyze middle ear structures critical for cochlear implantation using computed tomography. MATERIALS AND METHODS: Patients who underwent cochlear implantation at the Department of Otolaryngology in Szczecin between 2015 and 2022 were eligible for the study. We analyzed computed tomography images of 57 ears in 52 patients. The following parameters were assessed: mastoid aeration, tegmen tympani height, sigmoid sinus position, posterior tympanotomy width, the distance between the facial nerve and chorda tympani, modified facial recess distance, and the prediction line described by other authors. RESULTS: In 69% of patients, after the removal of the round window bony overhang, the round window membrane became fully visible. There were no statistically significant correlations found for parameters describing mastoid process anatomy or those rating the width of the posterior tympanotomy concerning round window access. The prediction lines, according to Kashio and Jwair, were found to be relevant. In cases where patients' access to the niche and membrane of the window was rated as good or very good during clinical evaluation, they were more likely to describe the window as being located posteriorly or medially in the radiological evaluation. Using a binary Jwair scale provided a better correlation with the clinical assessment. In cases where the windows were graded as posterior, the clinical assessment indicated better surgical access, especially to the RWM (Round Window Membrane). CONCLUSIONS: Evaluating middle ear anatomy on a computed tomography scan is useful for preparing for middle ear surgery but does not significantly affect the ability to access the round window. For such access, the position of the window in relation to the facial nerve is the most relevant factor, and measurements based on this relationship hold the highest clinical value.

The Clinical Relevance of Selected Cytokines in Newly Diagnosed Multiple Myeloma Patients.

Multiple myeloma (MM) is the second most common hematological neoplasm. Cytokines, chemokines, and their receptors, induced by the microenvironment of MM, participate in tumor growth, the attraction of leukocytes, cell homing, and bone destruction. This study aimed to assess the correlation between the pretreatment serum concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), angiogenic chemokine monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF) and the clinical outcomes and survival of patients newly diagnosed with MM. The study group consisted of 82 individuals. The IL-8 concentration was significantly positively correlated with the age of onset (p = 0.007), the International Staging System (ISS) stage (p = 0.03), the Eastern Cooperative Oncology Group (ECOG) performance status (p < 0.001), the degree of anemia before treatment (p < 0.0001), the degree of kidney disease (p < 0.001), and VEGF (p = 0.0364). Chemotherapy responders had significantly lower concentrations of IL-8 (p < 0.001), IL-6 (p < 0.001), and VEGF (p = 0.04) compared with non-responders. Patients with treatment-induced polyneuropathy had significantly higher levels of IL-8 (p = 0.033). Patients with a high level of IL-6 had a 2-fold higher risk of progression-free survival (PFS) reduction (17 vs. 35 months; HR = 1.89; p = 0.0078), and a more than 2.5-fold higher risk of overall survival (OS) reduction (28 vs. 78 months; HR = 2.62; p < 0.001). High levels of IL-6, IL-8, and VEGF demonstrated significant predictive values for some clinical conditions or outcomes of newly diagnosed MM patients. Patients with an early response to chemotherapy had a significantly lower concentration of these cytokines. A high pretreatment IL-6 concentration was an independent negative prognostic marker for newly diagnosed MM patients.

Circulating Serum MiRNA-8074 as a Novel Prognostic Biomarker for Multiple Myeloma.

MiRNA-8074 is a molecule with the potential to regulate the expression of key genes related to the pathogenesis of multiple myeloma (MM), i.e., TP53, MYC, MAPK1, and KIAA. We analyzed the predictive and prognostic value of miRNA-8074 expression in MM patients. In total, 105 newly diagnosed MM patients treated with thalidomide (n = 27), bortezomib (n = 41) and bortezomib with thalidomide (n = 37) were studied. For miRNA analysis, the column method and the Real-Time PCR technique with specific TaqMan Fast Advanced Master Mix and TaqMan probes were used. Factors that were associated with a significant reduction in progression-free survival (PFS) included: ECOG > 1, ISS stage III, low hemoglobin, thrombocytopenia, hypoalbuminemia, abnormal renal function, elevated creatinine, GFR < 60 mL/min/1.73 m2, elevated LDH, del(17p), t(11;14), the use of a single drug regimen (thalidomide or bortezomib) and high miRNA-8074 expression (HR = 2.01, 95% CI: 1.16-3.49; p = 0.0233). In addition to the known prognostic factors, such as ECOG > 1, Durie-Salmon stage III, diagnosis of light chain disease or non-secreting MM, renal failure, hypoalbuminemia, hypercalcemia, high ß2-microglobulin, elevated LDH, and t(14;16), a high expression of miRNA-8074 was significantly associated with a higher risk of death (HR = 4.12, 95% CI: 2.20-7.70; p = 0.0009). In summary, miRNA-8074 may be a useful diagnostic tool to assess the prognosis in MM patients.

SARS-CoV-2 Seroprevalence in Healthcare Workers before the Vaccination in Poland: Evolution from the First to the Second Pandemic Outbreak.

Healthcare workers (HCWs) are on the frontline, struggling with the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To describe recent or past infections, the serological assays enabled the assessment of the immune response developed in coronavirus disease (COVID-19) in the period when testing was hardly available. In this study, we investigated SARS-CoV-2 seroprevalence in HCWs in a Polish teaching hospital and the Regional Occupational Medicine Center after both the first and the second waves. ELISA-based tests for anti-SARS-CoV-2 IgA and IgG were used to determine immune response to SARS-CoV-2 in volunteer HCWs who worked in those institutions in May 2020 (208 participants aged 47.1 ± 12.5, 88% women) and in December 2020 (179 participants aged 45.2 ± 12.4, 86% woman). Risk factors for seropositivity were also assessed using a questionnaire filled out by all participants. We reported a significant increase in seroprevalence after the second wave (22.9%) compared with the first outbreak (2.4%) (OR 12.1; 95%CI 4.6-31.3; p < 0.0001). An association between IgG seroprevalence and severity of infections was noted. Furthermore, we demonstrated that amongst medical personnel, nurses exhibited a proportionally higher SARS-CoV-2 seroprevalence. Moreover, given the high seroprevalence in non-clinical group of HCWs, we suggest that community transmission can play a superior role to workplace exposure.

Expression of CTLA-4 and CD86 Antigens and Epstein-Barr Virus Reactivation in Chronic Lymphocytic Leukemia-Any Link with Known Prognostic Factors?

Infection with Epstein-Barr virus (EBV) worsens the prognosis in chronic lymphocytic leukemia (CLL), but the underlying mechanisms are not yet established. We intended to assess whether EBV affects the course of CLL by the deregulation of the CTLA-4/CD86 signaling pathway. We used polymerase chain reaction to measure the load of EBV DNA in the blood of 110 newly diagnosed patients with CLL. The expression of CTLA-4 and CD86 antigen on lymphocytes was assessed with flow cytometry. Additionally, CTLA-4 and CD86 serum concentrations were measured through enzyme-linked immunosorbent assays. Fifty-four percent of the patients had detectable EBV DNA [EBV(+)]. In EBV(+) patients the CTLA-4 and CD86 serum concentrations and their expressions on investigated cell populations were significantly higher than in EBV(-) patients. EBV load correlated positively with unfavorable prognostic markers of CLL and the expression of CTLA-4 on CD3+ lymphocytes (r = 0.5339; p = 0.027) and CD86 on CD19+ cells (r = 0.6950; p < 0.001). During a median follow-up period of 32 months EBV(+) patients were more likely to require treatment or have lymphocyte doubling (p < 0.001). Among EBV(+) but not EBV(-) patients, increased expressions of CTLA-4 lymphocytes were associated with elevated risks of progression. We propose that EBV coinfection may worsen prognosis in CLL patients, partly due to EBV-induced up-regulation of CTLA-4 expression.

Influence of Radiographic Bone Quality on the Type of Proximal Humerus Fracture.

BACKGROUND: The risk of proximal humerus fractures increases with age and deterioration of bone quality over time, and the treatment of these injuries may be clinically challenging.The aim of this study was to analyse the relationship between local bone quality and the morphology of proximal humerus fractures. MATERIAL AND METHODS: We conducted a retrospective study of 187 patients diagnosed with proximal humerus fractures. X-ray images of all patients were analysed, and on this basis, bone quality was assessed, using the Deltoid Tuberosity Index (DTI), average cortical bone thickness (CBTavg) and the Tingart measurement. The type of fracture was classified according to Neer's and Association for Osteosynthesis (AO) classifications. Moreover, the caput-collum-diaphyseal (CCD) angle was measured and the relationships between valgus or varus fractures and the DTI, CBTAVG and Tingart parameters were investigated in all patients. RESULTS: Using the Neer classification, the most common fracture type was type 3, found in 90 patients (48.1%). A total of 51 patients (27.3%) sustained an AO B1 fracture. Significantly lower mean DTI values were noted in patients with a Neer 4 fracture compared to those with Neer 3 (p = 0.02) and Neer 2 fractures (p = 0.03). Moreover, significantly higher mean DTI (p <0.00) and CBTAVG (p <0.025) values were noted in the group of patients with valgus fractures (CCD> 140º). CONCLUSIONS: 1. In the group of patients diagnosed with a four-part fracture according to Neer, bone quality assessed using the Deltoid Tuberosity Index was significantly worse than in two- and three-part fractures. 2. Significantly higher bone quality, assessed on the basis of the DTI and CBTAVG indices, was observed among patients with valgus fractures compared to those with varus fractures.

Quality of Life of Men after Cementless Hip Replacement - a Pilot Study.

BACKGROUND: Hip osteoarthritis is a significant health, social and economic problem. The associated pain and pathological and pathological proliferative joint lesions significantly reduce patients' quality of life. MATERIAL AND METHODS: The study involved 61 male patients aged 30 to 75 years qualified for hip arthroplasty due to osteoarthritis. A short version of the WHOQoL-BREF and EQ-5D-5L questionnaires were used to assess the quality of life. The questionnaires were administered before surgery, during the first outpatient visit (6 weeks after the surgery) and 6 months after the surgery. RESULTS: The WHOQoL-BREF questionnaire showed that the quality of life had improved significantly after just 6 weeks by 5% and 19% (p <0.01). After 6 months, there was also an improvement, of 13% and 42% (p <0.001). The most marked statistical improvement was found in the somatic domain after 6 weeks (8%) and after 6 months (11%) (p <0.001). The quality of life according to the EQ-5D-5L questionnaire showed statistically significant improvement of 13-23% after 6 weeks and of 32-42% after 6 months (p <0.001). The most marked improvement was achieved in terms of pain relief (p <0.001). CONCLUSIONS: 1. The quality of life improved significantly after just six weeks following hip arthroplasty. 2. The results were significantly higher also after 6 months. 3. The functional status of the patients improved significantly at both 6 weeks and 6 months after hip arthroplasty, especially in terms of pain reduction.

Serum brain-derived neurotrophic factor (BDNF) concentration predicts polyneuropathy and overall survival in multiple myeloma patients.

Brain-derived neurotrophic factor (BDNF) is a protein with a potent influence on several aspects of neuronal and blood vessel functions. However, its prognostic potential and functional role in multiple myeloma (MM) remain largely unknown. In this study, we investigated the influence of BDNF on the risk of chemotherapy-induced peripheral neuropathy (CIPN) and clinical outcome. Study group consisted of 91 newly-diagnosed MM patients treated with bortezomib and/or thalidomide-based chemotherapy. Detection of BDNF in serum was performed using ELISA. Polyneuropathy was assessed according to the CTCAE Criteria v5. We observed that BDNF concentration correlated with the severity of polyneuropathy (P = 0·0463). Higher BDNF values were noted in patients who responded to treatment (P = 0·0326), and BDNF proved to be a useful marker to predict lack of response after eight cycles of treatment (sensitivity - 100%, specificity - 61·5%, P = 0·0142). Moreover this marker showed significant diagnostic usefulness in diagnosis of CIPN (sensitivity - 76%, specificity - 71·43%; area under the curve (AUC)= 0·77, 95%, confidence interval (CI): 0·64-0·88; P < 0·0001). Low BDNF was an independent, unfavourable prognostic factor associated with reduced overall survival (OS) (hazard ratio (HR) = 2·79, P = 0·0470). In conclusion, BDNF level may play a prognostic role and constitute a useful biomarker in predicting CIPN in MM patients.

Prognostic value of pretreatment neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in multiple myeloma patients treated with thalidomide-based regimen.

Neutrophils to lymphocytes ratio (NLR) and platelets to lymphocytes ratio (PLR) are considered as laboratory markers of inflammation. They can be potentially useful in predicting the course of multiple neoplasms including selected hematological cancers. The aim of the study was to assess the value of NLR and PLR in predicting the effects of therapy and prognosis in multiple myeloma patients treated with thalidomide-based regimen. The study group consisted of 100 patients treated with the first line CTD (cyclophosphamide, thalidomide, and dexamethasone) chemotherapy. The NLR and PLR were calculated before treatment. High NLR was observed in patients with higher stage of the disease, with poor performance status, hypercalcemia, and high CRP. High PLR was associated with low BMI and high CRP. In patients with high NLR, significantly shorter PFS was observed (17 vs. 26 months, p = 0.0405). In addition, high values of NLR and PLR were associated with significantly shorter OS (38 vs. 79 months, p = 0.0010; 40 vs. 78 months, p = 0.0058). Summarizing, NLR and PLR have a significant independent prognostic value for multiple myeloma patients. Furthermore, the NLR can be a predictive marker for the outcome of thalidomide-based chemotherapy.

Can atopy have a protective effect against cancer?

BACKGROUND: An increased prevalence of allergies and an increased incidence of breast cancer have been observed. The hypothesis that atopy may have a protective effect against the risk of different types of breast cancer was evaluated. METHODS: In this study, 11,101 patients (11,101 women with a mean age of 55.2±14.7 years) with different types of breast cancer were tested for allergies. Allergies were confirmed based on the retrospective analysis of allergy diagnostic procedures in patients who had been previously diagnosed with breast cancer. The retrospective prevalence rates of active allergic diseases, including allergic rhinitis, bronchial asthma and atopic dermatitis, were assessed. All patients were also analyzed for bronchial asthma and allergic rhinitis according to the relevant guidelines. A group of healthy control patients was used for the comparisons. RESULTS: The women with breast cancer had a significantly lower incidence of IgE-mediated allergic diseases than the controls. The odds ratios (ORs) for allergic rhinitis, atopic dermatitis, and bronchial asthma were 0.61 (95% CI: 0.57-0.73), 0.17 (95% CI: 0.11-0.44), and 0.73 (95% CI: 0.65-0.83), respectively. The mean serum concentrations of total IgE were significantly lower in the study population of women with breast cancer than in the patients of the control group (39.2 ± 26.2 kU/L vs. 108.5 ± 38.5 kU/L; p = 0.002). CONCLUSION: Our results suggest that the overall incidence of allergies, especially allergic rhinitis, is lower in patients with certain types of cancer than in individuals who did not have cancer. Further studies are needed to confirm our findings.

THE INFLUENCE OF HIP ARTHROPLASTY ON HEALTH RELATED QUALITY OF LIFE IN MALE POPULATION WITH OSTEOARTHRITIS HIP DISEASE.

OBJECTIVE: Introduction: Hip osteoarthritis is a disabling disease which become substantial health-related, social, and economic issue. The aim: To assess short term quality of life in male population with hip ostheoarthritis, after total hip arthroplasty. PATIENTS AND METHODS: Material and methods: 118 male patients were included in the study, age range from 31 to 79 year-old, who underwent total hip arthroplasty. Patients quality of life was assessed using questioners: abbreviated version of WHOQoL-BREF, as well as EQ-5D-5L, and SF-36 scale. Patients condition was investigated before surgery, 6 weeks and 6 months after the surgery. RESULTS: Results: The results from WHOQoL-BREF questionnaire demonstrated a statistically significant improvement of quality of life after the surgery - 6 weeks after the procedure by 4% and 21% (p<0.001), after 6 months by 13% and 42% (p<0.001), respectively. The most significant improvement was found in the somatic domain - by 5% after 6 weeks, and by 6% after 6 months (p<0.001). The quality of life according to the EQ-5D-5L questionnaire revealed statistically significant improvement after 6 weeks, by 18-24% (p<0.001), after 6 months by 41-48% (p<0.001). Substantial improvement was achieved in reducing pain and improving mobility. SF-36 questionnaire showed statistically significant improvement after 6 months from the surgery in both physical (by 44%), and mental condition (by 54%) (p<0.001). CONCLUSION: Conclusions: Improvement of the quality of life - mainly less severe pain and better mobility after total hip arthroplasty in the investigated group of men was proven in 6 weeks after the procedure, while the further progress was more noticeable 6 months after the procedure.

CTLA-4 Expression Inversely Correlates with Kidney Function and Serum Immunoglobulin Concentration in Patients with Primary Glomerulonephritides.

Major causes of chronic kidney disease are primary proliferative and nonproliferative glomerulonephritides (PGN and NPGN). However, the pathogenesis of PGN and NPGN is still not fully understood. Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is a T-cell membrane receptor that plays a key role in T-cell inhibition. Despite its role in autoimmunological diseases, little is known about the involvement of CTLA-4 in the pathogenesis of PGN and NPGN. The objective of this study was to determine the role of CTLA-4 in the pathogenesis of PGN and NPGN by evaluating the frequencies of T and B lymphocytes expressing CTLA-4 and the serum concentration of the sCTLA-4 isoform in patients with PGN and NPGN in relation to clinical parameters. The study included peripheral blood (PB) samples from 40 PGN and NPGN patients and 20 healthy age- and sex-matched volunteers (control group). The viable PB lymphocytes were labeled with fluorochrome-conjugated monoclonal anti-CTLA-4 antibodies and analyzed using flow cytometry. The serum concentration of sCTLA-4 was measured using ELISA. The frequencies and absolute counts of CD4+/CTLA-4+ T lymphocytes, CD8+/CTLA-4+ T lymphocytes and CD19+/CTLA-4+ B lymphocytes and the serum sCTLA-4 concentration were lower in PGN and NPGN patients that in the control group. Reduced sCTLA-4 expression was associated with a lower concentration of serum immunoglobulins. Our results indicate that deregulation of CTLA-4 expression may result in continuous activation of T cells and contribute to the pathogenesis of PGN and NPGN.

Polymorphisms in the promotor region of the CRBN gene as a predictive factor for peripheral neuropathy in the course of thalidomide-based chemotherapy in multiple myeloma patients.

Thalidomide is commonly used in treatment of multiple myeloma (MM). This study aimed to analyse the influence of clinical and molecular factors - single nucleotide polymorphisms (SNPs) of the CRBN gene: rs6768972 and rs1672753, on the risk of adverse effects (AEs) of thalidomide-based chemotherapy in patients with MM. The study group included 82 patients receiving CTD (thalidomide, cyclophosphamide, dexamethasone) as first line treatment. The intensity of haematological and non-haematological AEs was assessed according to the Common Terminology Criteria for Adverse Events v4.03. Multivariate analysis showed that patients with the CRBN CC genotype (rs1672753) had more than a 14-fold higher risk of peripheral polyneuropathy compared to patients with other variants of the investigated SNP [odds ratio (OR) = 14·29]. Carriers of this genotype were burdened with significantly (about 17-fold) higher risk of diarrhoea during treatment (OR = 16·67). The presence of CRBN AA (rs6768972) or TT (rs1672753) genotypes was associated with about 333-fold and 250-fold lower risk of constipation in the course of therapy (OR = 0·003; OR = 0·004, respectively). Selected CRBN SNPs may be useful in assessing the probability of AEs in the form of peripheral polyneuropathy and gastrointestinal motility disorders associated with the use of thalidomide in patients with MM.

ACE Insertion/Deletion Polymorphism (rs4646994) Is Associated With the Increased Risk of Multiple Myeloma.

Introduction: The insertion (I allele) deletion (D allele) polymorphism of ACE gene (rs4646994) may influence the etiopathogenesis of multiple myeloma (MM). ACE gene is expressed in bone marrow cells and encodes angiotensin converting enzyme (ACE). It converts angiotensin I to active peptide angiotensin II, which stimulates proliferation of hematopoietic stem cells. This suggests possible association of ACE I/D gene polymorphism with MM. The aim of our study was to check possible impact of this polymorphism on risk of development and outcome of MM, as well as, sensitivity to bortezomib in cell cultures derived from MM patients. Objects and Methods: Genomic DNA from 98 newly diagnosed MM patients and 100 healthy blood donors were analyzed by PCR method. Chromosomal aberrations were detected by use of cIg-FISH. In a subgroup of 40 MM patients nucleated bone marrow cells were treated with bortezomib in vitro. Results: The Hardy-Weinberg equilibrium test showed that genotypic frequencies diverged significantly from the equilibrium. The differences between I and D allele frequencies in control and study population were significant (p = 0.046). We observed the association between DD genotype and more than 2-fold risk of MM - OR = 2.69; p < 0.0001. We did not detect any significant differences among studied genotypes regarding clinical and laboratory parameters. Moreover, we did not observe the association between survival of MM patients and I/D genotypes. Bortezomib increased number of apoptotic and necrotic cells, but the only statistically significant differences were observed in the number of viable cells at 1 nM between ID and DD genotypes (p = 0.026). Conclusion: Presented results confirmed the significant relationship between ACE (I/D) polymorphism and risk of MM development. We did not observe the association of ACE I/D polymorphism with disease outcome and bortezomib in vitro sensitivity.

Effectiveness of Haemophilus influenzae type b vaccination after splenectomy - impact on selected immunological parameters.

Splenectomy is a surgery indicated in case of splenic rupture after injury, when there are tumors in the spleen, or as a treatment for certain diseases, such as idiopathic thrombocytopenic purpura and spherocytosis. The aims of the study were to assess the immunological response to the Haemophilus influenzae type b (Hib) vaccine and the post-vaccination changes in lymphocyte subsets and cell activation markers in splenectomized patients and healthy volunteers. Blood samples were collected from 25 patients that had undergone splenectomy and from 15 healthy, non-splenectomized volunteers. All participants received a single dose of Hib vaccine. The concentration of specific Hib antibodies was assessed by an enzyme-linked immunosorbent assay. Selected immune cell populations were evaluated using flow cytometry. The analysis of the antibody titers against Hib showed statistically significant differences in both groups. There was a significantly higher percentage (p = 0.0012) and absolute value (p = 0.0003) of natural killer T (NKT)-like cells (CD3+/CD16+ CD56+) in the study group, compared to the control group. The levels of natural killer (NK) and NKT cells did not change relative to the cause and age of splenectomy. The quantity and percentage of regulatory T (Treg) cells were higher in the study group compared to the control group (p < 0.0001). No significant correlations were found between the time elapsed since splenectomy, the age of the patients, and the Treg levels. Our study showed that spleen resection results in an important deterioration of Treg cells and Th17 cell balance which may contribute to an incomplete immunological response.

Relationship between the expression of CD25 and CD69 on the surface of lymphocytes T and B from peripheral blood and bone marrow of patients with chronic lymphocytic leukemia and established prognostic factors of this disease.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is a condition characterized by the accumulation of morphologically mature monoclonal lymphocytes B with the CD19+/CD5+/CD23+ phenotype in lymphoid tissue, peripheral blood and bone marrow. The clinical course of patients with CLL is heterogeneous, ranging from indolent to aggressive. The role of lymphocyte activation in the natural history of CLL is still a matter of discussion. OBJECTIVES: The aim of this study was to determine the percentages and absolute numbers of lymphocytes B and T in peripheral blood and bone marrow of CLL patients. Moreover, we analyzed the relationship between the number of CD25-positive and CD69-positive lymphocytes and the established prognostic factors in CLL. MATERIAL AND METHODS: The study included 80 untreated patients with CLL and 20 healthy subjects. The immunophenotype of peripheral blood mononuclear cells (in both groups) and bone marrow cells (solely in the CLL group) was determined by means of flow cytometry. RESULTS: Patients with CLL showed a higher absolute number of activated lymphocytes B with phenotypes CD19+CD25+ and CD19+CD69+, as well as a higher absolute number of CD3+CD25+ lymphocytes T than the controls. The enhanced activation of peripheral blood and bone marrow lymphocytes was associated with higher Rai stages, an increased concentration of lactate dehydrogenase and beta-2 microglobulin and the progression of the disease. The number of lymphocytes B CD19+ZAP-70+ correlated positively with the number of CD19+CD25+ B cells and CD3+CD69+ T cells. CONCLUSIONS: The study confirmed the association between an unfavorable prognosis and a high expression of activation markers in CLL patients. The determination of CD25+ and CD69+ lymphocytes T and B constitutes a valuable diagnostic tool, completing the cytometric evaluation of CLL.

Deviations in Peripheral Blood Cell Populations are Associated with the Stage of Primary Biliary Cholangitis and Presence of Itching.

To evaluate the role of Th17, Treg cells, activated T CD3+ and B CD19+ lymphocytes in primary biliary cholangitis (PBC) patients. 40 female patients with PBC and 20 healthy donors were enrolled in this study. The percentages and absolute counts of Th17, Treg, activated T CD3+, B CD19+, NK, NKT-like lymphocytes were measured by flow cytometry. Our research revealed significantly lower frequencies and absolute counts of CD4+CD25+FOXP3+ Treg cells (p < 0.0001), higher percentages and absolute counts of Th17 cells (IL-17A+CD3+CD4+; p < 0.0001 and p = 0.009, respectively), CD3-/CD16+CD56+ NK cells (p < 0.0001 and p = 0.039, respectively), CD3+/CD16+CD56+ NKT-like cells (p < 0.0001 and p = 0.048, respectively). There were also higher percentages and numbers of B CD19+ lymphocytes (p = 0.002 and p = 0.001, respectively) and higher percentages and absolute counts of activated B CD19+CD25+ cells (p = 0.007 and p = 0.002, respectively). Moreover, we observed a statistically significant correlation between the presence of itching and particular peripheral blood subpopulations in PBC patients. Absolute counts of both CD4+CD3+ cells (p = 0.0119) and CD3+CD25+ cells (p = 0.0329) were lower in patients with pruritus. A similar dependency was noted in reference to percentages of NKT-like cells (CD3+/CD16+CD56+; p = 0.0359) and (CD3+) T lymphocytes (p = 0.0302). Th17 and Treg cells are involved in the course of PBC. There is also the association between the pruritus and peripheral blood subpopulations.

Male gender and age range 20-29 years are the most important non-modifiable risk factors for recurrence after primary post-traumatic shoulder dislocation.

PURPOSE: The aim of the study was to identify and analyze non-modifiable risk factors for recurrence after a first-time post-traumatic dislocation of the shoulder in the entire Polish population. METHODS: The entire Polish population was included in a cohort study. Patients diagnosed with primary post-traumatic dislocation of the shoulder between January 1st, 2010 and December 31st, 2011 were identified and followed up from January 1st, 2010 to December 31st, 2014. Incidence and recurrence rates and odds ratios (OR) were calculated. Demographic data were obtained from Poland's Central Statistical Office. Data on the number of patients with primary post-traumatic shoulder dislocation were drawn from the National Health Fund database. RESULTS: A total of 21,739 patients (14,466 males and 7273 females) with a primary shoulder dislocation in Poland were identified in 2010 and 2011. There were 3341 (15.4%) recurrences. Increased risk of recurrence was associated with male gender (OR = 1.92, 95% CI 1.76-2.09, p < 10-10) in the age range of 20-29 years (OR = 2.59, 95% CI 2.38-2.83, p < 10-10). The highest risk of first-time shoulder dislocation was revealed among females in the age group ≥ 80 years (OR = 24.1, 95% CI 22.6-25.7, p < 10-10). The risk of recurrence in the same group was significantly decreased (OR = 0.41, 95% CI 0.32-0.51, p < 10-10). CONCLUSION: Male gender and age range 20-29 years are highest population risk factors for recurrence after primary shoulder dislocation. Female gender and age ≥ 80 years are highest risk factors for the first-time post-traumatic dislocation of the shoulder joint and protective factors for recurrences after the first-time shoulder dislocation. LEVEL OF EVIDENCE: III.