De novo accelerated phase of chronic myeloid leukemia should be recognized even in the era of tyrosine kinase inhibitors.

Overall survival of patients classified according to the European LeukemiaNet 2020 classification. Chronic phase (CP), accelerated phase (AP), blast crisis (BC), low risk (LR), intermediate risk (IR), high risk (HR).

Perceptions of healthcare providers on benefits, risks and barriers regarding intradialytic exercise among haemodialysis patients.

PURPOSE: Clinical guidelines call for the inclusion of exercise interventions in every patient's dialysis session, but these recommendations are rarely adopted. Healthcare providers play a key role in this. Therefore, the aim of this study was to explore how healthcare providers perceive the benefits, risks and barriers of intradialytic exercise (IDE). METHODS: We conducted 21 individual, semi-structured interviews with 11 nurses, 5 nephrologists, 3 training assistants and 2 managers from two dialysis centres in Slovakia. Verbatim transcripts of digitally recorded interviews were thematically analysed using MAXQDA®. RESULTS: Participants reported the benefits of IDE as improvements in patients' physical and psychosocial functioning, independence and self-efficacy, clinical profile and quality of therapy. As risks of IDE, they most frequently reported exercise-related damage to vascular access, insufficient individualization of training and musculoskeletal injuries. The presence of psychological problems among patients was reported as a major barrier for initiating and maintaining patients' exercise. Other reported barriers included limitations in financial and personnel resources of haemodialysis care. CONCLUSIONS: Safe and sustainable implementation of IDE, which might improve a patient's well-being, need to be prescribed in alignment with the patient's clinical profile, be delivered individually according to the patient's characteristics and requires adjustments in the available resources.

Low Health Literacy Is Associated with Poorer Physical and Mental Health-Related Quality of Life in Dialysed Patients.

Health-related quality of life (HRQoL) is an important health indicator in chronic diseases like kidney diseases. Health literacy (HL) may strongly affect HRQoL, but evidence is scarce. Therefore, we assessed the associations of HL with HRQoL in dialysed patients. We performed a cross-sectional study in 20 dialysis clinics across Slovakia (n = 542 patients, mean age = 63.6 years, males = 60.7%). We assessed the association of categorised HL (low, moderate, high) with the SF36 physical component score (PCS) and mental component score (MCS) using generalised linear models adjusted for age, gender, education, and comorbidity (Charlson Comorbidity Index, CCI). We found significant associations of HL with PCS and MCS in dialysed patients, adjusted for age, gender, education, and CCI. Low-HL patients had a lower PCS (B = -3.27, 95%-confidence interval, CI: -5.76/-0.79) and MCS (B = -6.05, 95%-CI: -8.82/-3.29) than high-HL patients. Moderate-HL patients had a lower MCS (B = -4.26, 95%-CI: -6.83/-1.69) than high-HL patients. HL is associated with physical and mental HRQoL; this indicates that dialysed patients with lower HL deserve specific attention and tailored care to have their HRQoL increased.

Strategies for the Psychological Support of the Healthcare Workforce during the COVID-19 Pandemic: The ERNST Study.

The COVID-19 pandemic led to the implementation of interventions to provide emotional and psychological support to healthcare workers in many countries. This ecological study aims to describe the strategies implemented in different countries to support healthcare professionals during the outbreak. Data were collected through an online survey about the measures to address the impact of the pandemic on the mental health of healthcare workers. Healthcare professionals, researchers, and academics were invited to respond to the survey. Fifty-six professionals from 35 countries contributed data to this study. Ten countries (28.6%) reported that they did not launch any national interventions. Both developed and developing countries launched similar initiatives. There was no relationship between the existence of any type of initiative in a country with the incidence, lethality, and mortality rates of the country due to COVID-19, and per capita income in 2020. The 24 h hotline for psychological support was the most frequent intervention. Tools for self-rescue by using apps or websites were extensively used, too. Other common interventions were the development of action protocols, availability of regular and updated information, implantation of distance learning systems, early detection of infection programs for professionals, economic reinforcements, hiring of staff reinforcement, and modification of leave and vacation dates.

Health Literacy and Change in Health-Related Quality of Life in Dialysed Patients.

Health-related quality of life (HRQoL) is likely to deteriorate with the progression of chronic kidney disease (CKD). This change may be worsened by low health literacy (HL). We performed a longitudinal study at over 20 dialysis clinics in Slovakia (n = 413; mean age = 64.8 years; males = 58.4%). We assessed the association of three HL groups with a change in HRQoL over two years using binary logistic regression adjusted for type of vascular access, dialysis effectiveness, comorbidity, age and gender. We found that patients with low HL had poorer HRQoL at baseline in comparison to high-HL patients. We did not find significant associations of lower HL with the deterioration of mental or physical HRQoL after two years. In the adjusted model, patients with lower HL were not more likely to have deteriorated physical (low-HL patients: odds ratio/95% confidence interval: 0.99/0.53-1.84; moderate-HL patients: 0.97/0.55-1.73) or mental HRQoL (low-HL patients: 1.00/0.53-1.87; moderate-HL patients: 0.95/0.53-1.70) in comparison to high-HL patients. The HRQoL of lower-HL patients is worse at baseline but develops similarly to that of high-HL patients during dialysis treatment. Their relative HRQoL, thus, does not worsen further, but it does not improve either. Tailoring care to their needs may help to decrease the burden of low HL in dialysed patients.

The effects of an intradialytic resistance training on lower extremity muscle functions.

PURPOSE: The loss of muscle functions is a significant health issue among dialysis patients. Poor muscle strength negatively affects a patient's mobility, independence and quality of life. The aim of the study was to assess the effects of an intradialytic resistance training (IRT) on lower extremity muscle functions among dialysed patients. MATERIALS AND METHODS: Ninety patients were allocated into an experimental group (n = 57) or control group (CNG) (n = 33) according to the location of the dialysis service center. Fifty-eight patients completed the study follow-up. The intervention regarded 12-week IRT, while the controls remained physically inactive during hemodialysis. In both groups of patients, we assessed lower extremity muscle functions by a diagnostics of maximal isometric force generated during hip flexion (HF), hip extension (HE), and knee extension (KE) contractions at baseline, after the 12-weeks intervention and after a further 12-weeks follow up. RESULTS: We found that improvements in HE between baseline and post-intervention were significantly larger for the experimental than the CNG (difference 32.0, 95% CI = 12.3-51.8, p = 0.002). For the other primary outcomes, we found no differences between the groups, and neither for the two other indices of muscle strength (HF and KE). At 12-weeks follow-up, we found no statistically significant differences between the two groups. CONCLUSIONS: Our findings indicate that exercise during dialysis not just suppresses adverse effects in muscle strength and functioning, but effectively and safely increases lower extremities muscle function in a relatively short time.Implications for RehabilitationRegular, progressive, resistance training realized during dialysis is well tolerated and safe for exercise interventions in hemodialysis patients.A 12-weeks intradialytic resistance training is effective in the prevention and clinical management of muscle function loss among hemodialysis patients.The range of improvements in muscle functions, demonstrated by the assessment of maximal isometric force, varied severely during different lower extremity movements of hemodialysis patients.

Health-Related Quality of Life Profiles in Dialyzed Patients With Varying Health Literacy. A Cross-Sectional Study on Slovak Haemodialyzed Population.

Objectives: Chronic kidney disease (CKD) strongly affects patients' health-related quality of life (HRQoL), mostly in the advanced stages of CKD. Health literacy (HL) may affect this association, in particular for some aspects of HRQoL. The aim of this study is to compare the profiles of HRQoL in dialyzed patients with varying HL. Methods: We obtained data on HL using the Health Literacy Questionnaire (HLQ) and on HRQoL using the Kidney Disease Quality of Life - Short Form (KDQoL-SF 1.3) in a multicentre cross-sectional study in 20 dialysis clinics in Slovakia (n = 542; mean age = 63.6 years; males: 60.7%). We compared HRQoL for three HL groups using ANOVA and the Kruskal-Wallis test. Results: Patients with low HL reported worse HRQoL than patients with moderate and high HL. The greatest differences between HL groups were found in the scales Effect of kidney disease, Cognitive function, Quality of social interaction, Social support, Dialysis staff encouragement, Patient satisfaction, Physical functioning, Pain, Emotional well-being and Social function. p-values in all cases were <0.001. Conclusion: Patients with low HL have a worse HRQoL in several domains than patients with a higher HL. Increasing HL capacities and better supporting patients with low HL should thus be given priority to support their HRQoL and at least maintain its level.

Does Depression and Anxiety Mediate the Relation between Limited Health Literacy and Diet Non-Adherence?

Limited health literacy (HL), depression and anxiety are common in dialyzed patients and affect health outcomes and self-management. We explored whether depression and anxiety mediate the association of HL with diet non-adherence (DN-A) in dialyzed patients. We performed a cross-sectional study in 20 dialysis clinics in Slovakia (n = 452; mean age: 63.6 years; males: 60.7%). Hierarchical cluster analysis was performed to create three HL groups. Logistic regression adjusted for age, gender and education was used to explore whether depression and anxiety mediate the association of HL with DN-A. Patients in the moderate HL group were more likely to be non-adherent to diet (OR (Odds Ratio)/95% CI: 2.19/1.21-3.99) than patients in the high HL group. Patients in the low HL and moderate HL group more likely reported depression or anxiety. Patients reporting depression (OR/95% CI: 1.94/1.26-2.98) or anxiety (OR/95% CI: 1.81/1.22-2.69) were more likely to be non-adherent with diet. Adjustment for depression reduced the association between moderate HL and DN-A by 19.5%. Adjustment for anxiety reduced the association between moderate HL and DN-A by 11.8%. Anxiety and depression partly mediated the association of HL with DN-A. More attention should be paid to treating patients' psychological distress to ensure adequate adherence with recommended diet.

Does Health Literacy of Hemodialyzed Patients Predict the Type of Their Vascular Access? A Cross-Sectional Study on Slovak Hemodialyzed Population.

Effective vascular access (VA) is an essential condition for providing hemodialysis, affecting patients' health outcomes. We aim to explore how health literacy (HL) as a non-clinical factor is associated with the decision-making process regarding VA type selection. Using data from 20 dialysis centers across Slovakia (n = 542, mean age = 63.6, males = 60.7%), the association of HL with type of VA (arteriovenous fistula (AVF) vs. central venous catheter (CVC)) was analyzed using a logistic regression model adjusted for sociodemographic characteristics and comorbidity. Sociodemographic data and data on nine domains of HL were collected by questionnaire. Data on VA and comorbidity were obtained from a medical records. Patients with a greater ability to engage with healthcare providers (odds ratio (OR): 1.34; 95% confidence interval (CI): 1.00-1.78), those with a better ability to navigate the healthcare system (OR: 1.41; 95% CI: 1.08-1.85), those more able to find good health information (OR: 1.52; 95% CI: 1.15-2.03), and those who understand it well enough to know what to do (OR: 1.52; 95% CI: 1.12-2.06) are more likely to have AVF. Patients' HL is associated with the type of VA; therefore, it should be considered in the decision-making process regarding the selection of the type of VA, thereby informing strategies for improving patients' HL and doctor-patient communication.

Is Health Literacy of Dialyzed Patients Related to Their Adherence to Dietary and Fluid Intake Recommendations?

Non-adherence to dietary and fluid intake recommendations (NADFIR) is an important factor for the effective treatment of dialyzed patients and may be hindered by low health literacy (HL). Therefore, we assessed whether low HL of dialyzed patients is associated with their NADFIR. We performed a multicentric cross-sectional study in 20 dialysis clinics in Slovakia (n = 452; response rate: 70.1%; mean age = 63.6 years; males: 60.7%). We assessed the association between nine domains of HL and non-adherence (high serum potassium, high serum phosphate, relative overhydration, and self-reported NADFIR) using general linear models adjusted for age and gender. Moreover, we assessed the moderation by socioeconomic status (SES). We found higher NADFIR among patients with less sufficient information for health management (high serum phosphate level; odds ratio (OR): 0.77; 95% confidence interval (CI): 0.63-0.94), with a lower ability to actively manage their health (self-reported diet non-adherence; OR: 0.74; 95% CI: 0.62-0.89), and those less able to actively engage with healthcare providers (overhydrated; OR: 0.78; 95% CI: 0.65-0.94). Moreover, SES modified this relation. Low HL affects the adherence of dialyzed patients. This shows a need to support patients with low HL and to train healthcare providers to work with these patients, taking into account their SES.

The effects of intradialytic resistance training on muscle strength, psychological well-being, clinical outcomes and circulatory micro-ribonucleic acid profiles in haemodialysis patients: Protocol for a quasi-experimental study.

BACKGROUND: Intradialytic resistance training (IRT) protects patients' muscle mass and functions against protein-energy wasting, malnutrition and cachexia. However, the evidence of the effects of such an intervention in haemodialysis patients is limited and not conclusive. To improve the applicability of such interventions, we need a better understanding of molecular, functional and psycho-social adaptation in dialysed patients following a physical training. Therefore, the aim of this study is to investigate the effects of IRT on lower extremity muscle functions, quality of life, and anxiety and depression, clinical outcomes and circulatory micro-ribonucleic acid (miRNA) profiles in patients on chronic haemodialysis therapy. METHODS: We will perform a quasi-experimental study in 3 dialysis centres. Patients will be recruited via their nephrologists and will be allocated to an experimental and a control group based on the location of the patients' dialysis centre. Patients allocated to the experimental group will undergo a 12-week IRT, while the control group will remain physically inactive during dialysis. The primary outcome is the change in the maximal force produced during an isometric contraction of lower extremity muscles. Secondary outcomes regard quality of life, anxiety and depression, clinical outcomes and circulatory miRNA profiles. Patients' level of health literacy defined as the ability to get and understand health information will be also measured in the study as a potential modifier of effects. DISCUSSION: This quasi-experimental study can add in an important way to our understanding of the effects of resistance training on dialysis patients' muscle strength, quality of life and disease-specific outcomes.

HLA-B gene somatic insertion/deletion mutations in patients with acute myelogenous leukaemia.

Loss of heterozygosity is considered to be the most common type of tumour-specific somatic mutation of the human leucocyte antigens (HLA) genes in patients with haematological malignancies. Nevertheless, subtle DNA sequence changes, namely short insertions/deletions, may also abolish the expression of HLA molecules and interfere with routine HLA typing. Two male patients with acute myelogenous leukaemia (AML) were indicated for the search of a suitable donor for allogeneic haematopoietic stem cell transplantation (aHSCT). The patients and their relatives were initially HLA typed by serological and DNA techniques at a low-resolution level. The HLA high-resolution (HR) type was obtained by means of sequencing-based typing (SBT). In both cases, anomalous frameshifts in the sequence were observed in the HLA-B gene, namely in exon 3 (Case 1, heterozygous deletion of two bases) and exon 4 (Case 2, heterozygous insertion of two bases). In the second case, the insertion variant was associated with a loss of HLA-B8 expression. To reveal whether these sequence patterns may be caused by somatic mutations in the malignant cells, blood sample in remission (Case 1) and buccal swab sample (Case 2) were collected from the patients. In an important manner, the SBT in these germline samples revealed common HLA-B*07:02,*15:01 (Case 1) and HLA-B*08:01,*35:02 (Case 2) types with no evidence for the sequence alteration observed in the initial samples. In conclusion, the insertion/deletion sequence variants of the HLA-B gene in two patients were limited to the initial blood samples with a substantial proportion of AML cells and thus may be attributed to the somatic mutation in the malignant cells. HLA somatic mutations should be taken into account in patients with haematological malignancies to prevent HLA mistyping and inappropriate selection of an aHSCT donor.

A lower dosage of imatinib is sufficient to maintain undetectable disease in patients with chronic myeloid leukemia with long-term low-grade toxicity of the treatment.

The information about chronic myeloid leukemia (CML) patients with a deep molecular response of ≥ 4.5 log reduction (MR4.5) in whom the dose of imatinib (IM) had to be reduced to relieve toxicity is insufficient. In 205 CML patients the dose of IM was reduced in 19 (31.2%) out of 61 patients with MR4.5. The patients (12 pretreated with interferon-alpha) achieved MR4.5 after an average of 27.7 months. The duration of MR4.5 before the reduction of the dose was 16-123 (mean = 56.7) months. After the IM reduction (200 mg daily to 400 mg twice weekly for 15-90 (mean = 48) months) MR4.5 or major molecular response (MMR) was maintained in 14 (73.7%) and 2 (10.5%) patients, respectively. Three patients who lost MMR (15.8%) after the discontinuation of IM regained MR4.5 after the reintroduction of a lower dose. A lower dosage of IM should be tested for the management of side effects in patients with MR4.5 in prospective studies.

Comparison of reduced conditionings combining fludarabine with melphalan or 3-day busulfan in patients allografted for myeloid neoplasms.

In the present study we compared outcomes of patients with myeloid neoplasms undergoing allogeneic hematopoietic stem cell transplantation after fludarabine-based regimens with melphalan (FM140) or 3-day busulfan (FB3). The FM140 and FB3 combinations were administered to 21 and 27 patients, respectively. Efforts for early reduction (from day +30 to 60) and discontinuation (until day +100 to 130) of prophylactic immunosuppression were a component of the post-transplant approach. Following FB3 patients suffered from more severe stomatitis (P = 0.013). In contrast, other manifestations of regimen-related toxicity were more frequent in the FM140 group (P = 0.048). There were no statistically significant differences in the development of graft-versus-host disease, non-relapse mortality, post-transplant remission rate, or relapse incidence. Two-year disease-free survival rates were comparable in the two cohorts (66 vs. 55 %; P = 0.751), and so were the overall survival rates (64 vs. 62 %; P = 0.715). The outcomes of allografted patients with myeloid neoplasms were comparable after the FM140 and FB3 regimens. Relatively high therapeutic response in both groups may have been influenced by early reduction and discontinuation of prophylactic immunosuppression followed by effective immunological control of the malignant clone.

Rituximab does not adversely affect the stem cell mobilization and engraftment after high-dose therapy and autologous transplantation in patients with diffuse large B-cell lymphoma in first complete or partial remission.

AIMS AND METHODS: The goal was to investigate the effect of prior combined rituximab (R) and intensive chemotherapy on peripheral blood stem cell mobilization and their engraftment after stem cell transplantation (ASCT) in 69 patients with poor-risk, diffuse large B-cell lymphoma (DLBCL). RESULTS: A statistically comparable median number of CD34+ stem cells was collected in both groups (13.80x10(6)/ kg in the non-R group and 7.81x10(6)/kg in the R group; p = 0.110). A trend toward greater number of CFU-GM was found in the non-R group (98.1x10(4)/kg) compared to the R group (76.6x10(4)/kg; p = 0.068). The non-R patients had a much higher median number of BFU-E (90.9x10(4)/kg) than the R patients (31.3x10(4)/kg; p = 0.001). CONCLUSIONS: Hematopoietic engraftment was rapid for both groups and no different between them. The 3-year event-free survival was 90.4 % in the R group and 67.2 % in the non-R group (p = 0.04), but there was no significant difference in the 3-year overall survival (94,7 % vs 83,5 %; p = 0.179).

Salivary neutrophils level as an indicator of bone marrow engraftment.

AIM: The aim of this study was to investigate the neutrophils level in saliva as an adequate alternative to other methods for evaluating the neutrophil engraftment after autologous stem cell transplantation (ASCT) in hemato-oncology. METHOD: A total of 35 patients treated for non-Hodgkin's lymphoma or multiple myeloma were stomatologically examined before planned high-dose chemotherapy with ASCT. After removal of potential foci of odontogenic infection all the patients underwent transplantation and during the treatment they were monitored for the level of neutrophils in saliva as a possible early indicator of the neutrophil engraftment. Neutrophil levels in saliva were compared to the neutrophil level in blood and to the degree of oral mucositis (the nurses study). RESULTS: An increase of salivary neutrophils in the mouth rinse of > 25 x 10/\6/l was identified as an early sign of successful neutrophil engraftment that occurred 1 to 2 days before the rise of neutrophils in peripheral blood (> 0.5- x 10/\9/l). CONCLUSIONS: Follow-up of neutrophil levels in saliva might be an adequate alternative to other methods for evaluating the neutrophil engraftment after ASCT in hemato-oncology.

Successful childbirth in a patient with chronic myelogenous leukemia treated with imatinib mesylate during early pregnancy.

AIMS: To report a case of successful pregnancy in a patient with chronic myelogenous leukemia treated with imatinib mesylate for the first 4 months of pregnancy. RESULTS: Imatinib mesylate is potentially teratogenic and its use during pregnancy in humans can lead to abortion or development of fetal abnormalities in nearly 40% of fully reported cases. We report a case of a 28-year-old woman who delivered a healthy child of normal weight after having been treated with imatinib for Ph1-positive CML during the first four months of her pregnancy. She refused advocated interruption and for the rest of the pregnancy was treated with interferon. The treatment was associated with a rapid 2-log increase in the leukemia clone measured by the real-time polymerase chain reaction. Reintroduction of imatinib after delivery resulted in achievement of the complete cytogenetic response again. CONCLUSIONS: We discuss possible strategies for successful management of pregnancy in CML patients treated with imatinib.

Expression of cytochrome P450 genes in CD34+ hematopoietic stem and progenitor cells.

Expression of major cytochrome P450 forms (P450) was followed in preparation of purified hematopoietic CD34+ stem and progenitor cells. Levels of transcripts as well as mature proteins were traced by quantitative real-time polymerase chain reaction and by Northern and Western blotting. P450 1B1 and P450 2E1 proteins and respective mRNAs were found in all cases. On the other hand, no expression of P450 3A4, P450 3A7, and P450 2C9 was found. The results showed that expression of various P450 enzymes starts at different stages of cell differentiation. Both P450 forms found are known to be connected with cancer cells and with activation of procarcinogens (P450 1B1, polycyclic aromatic hydrocarbons; P450 2E1, nitrosamines, and solvents). Hence, cells at the early stage of differentiation already may be influenced by interaction with xenobiotics. This fact should also be taken into consideration when hematopoietic cell transplant therapy is applied.