Influence of Aortic Arch Morphology on Renal Perfusion in Patients with Coarctation of the Aorta: An Exploratory Study.

Objectives: The configuration of the aortic arch, particularly a Gothic arch shape, in individuals with corrected coarctation of the aorta (CoA) has been associated with a decreased systolic wave amplitude across the arch, which could potentially impair renal perfusion and elevate the risk of arterial hypertension. This study aims to explore the relationship between the morphological characteristics of the aortic arch and their impact on renal perfusion in patients with CoA. Methods: Seventy-one subjects with corrected CoA underwent continuous 24 h ambulatory blood pressure monitoring, computed tomography to assess the aortic arch, and renal perfusion scanning. Subjects were stratified into three groups based on the height-to-width (H/W) ratio of their aortic arch: Group 1 with a H/W ratio of <0.65, Group 2 with a H/W ratio between 0.65 and 0.85, and Group 3 with a H/W ratio of >0.85. Results: Groups 1 and 2 (53,78% and 62.63%) presented with a higher hypertension prevalence of elevated blood pressure than Group 3 (38.89%). Notable variations were observed among the subjects in the time to peak perfusion (Tmax) in the left kidney across the groups. Group 1 showed a median Tmax at 0.27, Group 2 at 0.13, and Group 3 at -0.38 (p-value = 0.079). The differences in Tmax for the right kidney followed a similar trend but were not statistically significant (Group 1 at 0.61, Group 2 at 0.22, and Group 3 at 0.11; p-value = 0.229). Conclusions: This study suggests that variations in the aortic arch morphology might not significantly influence renal perfusion in CoA patients. This indicates the potential adaptability of the renal blood flow, which appears to compensate for reduced perfusion, thus minimizing adverse effects on the kidney function. This adaptability suggests an inherent physiological resilience, emphasizing the need for further targeted research to understand the specific interactions and impacts on treatment strategies for CoA.

Observation Safely Reduces the Use of the Computerized Tomography in Medium-to-Low-Risk Patients with Suspected Acute Appendicitis: Results of a Randomized Controlled Trial.

Objectives-The objective was to compare the effectiveness of observation in standard-of-care computed tomography (CT) in adult patients with suspected acute appendicitis (AA). Methods-Patients with clinically suspected AA and inconclusive diagnosis after primary clinical examination, laboratory examination, and transabdominal ultrasound (TUS) were eligible for the study, and they were randomized (1:1) to parallel groups: observation-group patients were observed for 8-12 h and then, repeated clinical and laboratory examinations and TUS were performed; CT group (control group) patients underwent abdominopelvic CT scan. The study utilized Statistical Analysis System 9.2 for data analysis, including tests, logistic regression, ROC analysis, and significance evaluation. Patients were enrolled in the study at Vilnius University Hospital Santaros Klinikos in Lithuania between December 2018 and June 2021. Results-A total of 160 patients (59 men, 101 women), with a mean age of 33.7 ± 14.71, were included, with 80 patients in each group. Observation resulted in a reduced likelihood of a CT scan compared with the CT group (36.3% vs. 100% p < 0.05). One diagnostic laparoscopy was performed in the observation group; there were no cases of negative appendectomy (NA) in the CT group. Both conditional CT and observation pathways resulted in high sensitivity and specificity (97.7% and 94.6% vs. 96.7% and 95.8%). Conclusions-Observation including the repeated evaluation of laboratory results and TUS significantly reduces the number of CT scans without increasing NA numbers or the number of complicated cases.

Reduced human leukocyte antigen mismatching is associated with more favourable outcomes after unrelated donor haematopoietic stem cell transplantation.

The patient-donor human leukocyte antigen (HLA) match remains the most important prognostic factor for successful unrelated donor haematopoietic stem cell transplantation (UD-HSCT). This single-centre study comprised 125 adult patients with malignant haematological diseases undergoing their first UD-HSCT. The primary goal of this study was to validate the impact of HLA matching on HSCT outcomes, specifically at the HLA-DPB1 and HLA-DRB3/4/5 loci. A multivariable Cox regression analysis with a backward selection algorithm was employed to assess the associations of selected prognostic factors with outcomes after UD-HSCT. Any HLA locus mismatch was found to be associated with an increased incidence of grade II-IV acute graft versus host disease (aGvHD) at 100 days (p = .031; hazard ratio [HR] 1.935) and 6 months (p = .004; HR 2.284) after HSCT. The results of the following analyses also confirmed the strong impact of HLA-DPB1-only mismatch on the incidence of grade II-IV aGvHD at 100-day (p = .006; HR 2.642) as well as at 6-month (p = .007; HR 2.401) time periods. The HLA-DPB1-only mismatch was also shown to be statistically significantly associated with lower relapse incidence (p = .034; HR 0.333). The impact of the HLA-DRB3/4/5 mismatch on outcomes was inconclusive, though the two and more HLA-DPB1 + DRB3/4/5-only mismatches showed a trend towards worse outcomes than a single mismatch. Based on our findings and those of more comprehensive studies, the extended HLA loci typing of patients and donors is suggested to avoid unexpected HLA mismatches during the UD selection.

Prognostic value of circulating T-lymphocyte subsets in advanced pancreatic cancer patients treated with mFOLFIRINOX or gemcitabine.

Advanced pancreatic ductal adenocarcinoma (PDAC) is commonly treated with a chemotherapy combination of mFOLFIRINOX or gemcitabine. However, predictive and prognostic factors for choosing a more appropriate treatment strategy are still lacking. This study aimed to evaluate how chemotherapy changes immune system parameters and whether these changes influence survival outcomes. We sought to identify an easily accessible marker to help choose the appropriate treatment. Patients with PDAC who were suitable for systemic chemotherapy were eligible for the study. Peripheral blood samples were obtained at baseline and after two months of treatment. Lymphocyte subsets were measured using flow cytometry. Correlation with clinical features and survival analyses were performed. In total, 124 patients were enrolled in this study. Seventy patients were treated with mFOLFIRINOX and 50 with gemcitabine monotherapy. Four patients could not be treated because of rapid deterioration. During overall survival analysis (OS), significant factors included age, Eastern Cooperative Oncology Group (ECOG) performance status, differentiation grade G3, carcinoma antigen (CA) 19-9 more than 100 kU/L, absolute white blood cell count, CD3 + CD8+, and CD8 + CD57-T lymphocytes. Natural killer CD3-CD56 + CD16 + and CD3-CD56 + CD16- and T regulatory CD4 + FOXP3 + and CD3 + CD56 + cells differed during treatment, but these differences did not influence the survival results. At baseline, CD8 + CD57- T lymphocyte count demonstrated a clear independent impact on progression-free survival and OS. Gemcitabine showed better survival in patients with extremely low baseline CD8 + CD57- levels. Therefore, circulating CD3 + CD8 + and CD8 + CD57- cells measured before treatment in PDAC may be considered prognostic and predictive biomarkers.

The Effects of Treatment on Peripheral Blood Immune Cell Profile in Pancreatic Ductal Adenocarcinoma (PDAC).

BACKGROUND/AIM: This study evaluated whether circulating lymphocytes, assessed by flow cytometry, is a prognostic biomarker in pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: We studied T cell subsets in blood samples from a cohort of 41 patients diagnosed with PDAC. Patients underwent surgery of the primary site and adjuvant chemotherapy or were treated with 1st line chemotherapy (mFOLFIRINOX regimen or gemcitabine alone). The changes in T cell subpopulations during treatment were evaluated at the initial diagnosis before surgery, and after 2 and 4 months. Friedman test was used for statistical analysis. RESULTS: A decline in CD19+ B lymphocytes, natural killer (NK) cells CD3-CD56+CD16+, and T regulatory cells CD4+FOXP3+ during treatment was observed. NKT-like cells CD3+CD56+ and cytotoxic T cells CD3+CD8+ tended to increase after two months and decrease after that. CONCLUSION: Statistically significant changes in lymphocyte counts in peripheral blood were detected in patients with PDAC during treatment.

Development of a Cardio-Oncology Service in Lithuania: Prediction, Prevention, Monitoring and Treatment of Cancer Treatment-Induced Cardiotoxicity.

Background: Advances in cancer therapy have dramatically improved outcomes for cancer pa-tients. However, cancer treatment can cause several cardiovascular (CV) complications, increasing cardiac mortality and morbidity in cancer patients and survivors. As a result, a new cardiology subspecialty­cardio-oncology (CO)­has been developed. The goals of CO are to understand the mechanism of the cardiotoxicity (CTX) of cancer therapies and invent the best monitoring and treatment strategies to improve the survival of cancer patients. Methods: We performed a retro-spective observational study reporting on the 6-year experience of the first CO service in Vilnius, Lithuania. Cancer patients were consulted by a single part-time specialist at Vilnius University Hospital. All new patients underwent blood tests, including cardiac biomarkers and advanced transthoracic echocardiogram (TTE) with stress protocol if indicated. During a follow-up, we evaluated the association of patient survival with such variables as age, gender, reasons for re-ferral, cancer location and stage, cardiovascular (CV) risk factors (RF), and rates and stage of CTX and treatment strategies. Results: 447 patients were consulted (70% females), and the median age was 64 years. Cardiovascular (CV) RF was common: 38.5% of patients had hypertension, almost 38% had dyslipidemia, 29% were obese, 10% were smokers, and 9% had diabetes. Nearly 26% of patients had a history of HF. Early biochemical cardiotoxicity was determined in 27%, early functional cardiotoxicity was seen in 17%, and early mixed cardiotoxicity­in 45% of referred patients treated with cardiotoxic cancer therapies. In addition, reduced left ventricular ejection fraction (LVEF) was found in 7% of patients. Beta-blockers (BB) were administered to 61.1% of patients, while angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) to 54.1% of patients. In addition, 18.3% of patients received loop diuretics and almost 12% mineralocorticoid receptor antagonists (MRA), respectively. A total of 143 patients died during the 6-year follow-up period. The leading cause of death was primarily cancer (92.3%). Only in 5.6% of patients, cardiovascular complications were reported as the cause of death, and 2.1% of deaths were due to the COVID−19 infection. We found that age (HR 1.020 [95% CI: (1.005−1.036)] p = 0.009); LV diastolic dysfunction (HR 1.731 [95% CI: 1.115−2.689] p = 0.015; NYHA stage II (HR 2.016 [95% CI: 1.242−3.272] p = 0.005; NYHA stage III (HR 3.545 [95% CI: 1.948−6.450] p < 0.001; kidney dysfunction (HR 2.085 [95% CI: 1.377−3.159] p = 0.001; previous cancer (HR 2.004 [95% CI: 1.219−3.295] p = 0.006); tumor progression (HR 1.853 [95% CI: 1.217−2.823] p = 0.004) and lung cancer (HR 2.907 [95%CI: 1.826−4.627] p < 0.001) were statistically significantly associated with the increased risk of all-cause death. Conclusions: CO is a rapidly growing subspecialty of cardiology that aims to remove cardiac disease as a barrier to effective cancer treatment by preventing and reversing cardiac damage caused by cancer therapies. Establishing a CO service requires a cardiologist with an interest in oncology. Continuous education, medical training, and clinical research are crucial to success. Age, previous cancer, tumor progression, kidney dysfunction, left ventricular diastolic dysfunction, and NYHA stages were associated with increased mortality.

Impact of Medical Treatment of Hemodynamically Significant Patent Ductus Arteriosus on Cerebral and Renal Tissue Oxygenation Measured by Near-Infrared Spectroscopy in Very Low-Birth-Weight Infants.

Background and objective: Hemodynamically significant patent ductus arteriosus (hsPDA) can cause ductal steal and contribute to poor outcomes in preterm infants. Near-infrared spectroscopy (NIRS) allows us to continuously evaluate regional tissue oxygenation (rSpO2) and perfusion changes in underlying organs. The aim of this study was to evaluate the effect of medical treatment for hsPDA on cerebral and renal rSpO2 in infants less than 32 weeks of gestational age, and older than 72 h of life. Materials and methods: Infants with a gestational age of <32 weeks with hsPDA were prospectively studied before and during medical treatment. Two-site (cerebral and renal) rSpO2 monitoring by NIRS was performed 1 h before treatment (T0) and 24 h (T1), 24−48 h (T2), 48−72 h (T3) after the infusion of the first drug dose. Results: A total of 21 infants were studied. The mean day of life at treatment initiation was 8.2 (SD, 2.75). The DA diameter, LA/Ao ratio, and resistive index in the anterior cerebral artery (RI ACA) were significantly lower after treatment (p < 0.05). There were no significant differences in cerebral rSpO2, cerebral fractional tissue oxygen extraction (FTOE), and SpO2 comparing different time points. A significantly higher renal SpO2 value was recorded at T2 as compared with T0 (75.0%, SD 4.9%, vs. 69.4%, SD 7.6%; p < 0.013), while for renal FTOE, a tendency to lower values at T2 was observed (0.18, SD 0.05, vs. 0.24, SD 0.09; p = 0.068). Conclusions: Late (later than 7 days postpartum) hsPDA medical treatment with paracetamol or ibuprofen completely closed the duct only in a small proportion of preterm infants, despite a statistically significant reduction in the DA diameter, LA/Ao ratio, and RI ACA. Continuous renal, not cerebral, NIRS measurements can help to anticipate the efficacy of medical treatment of hsPDA in preterm infants. Large-scale prospective studies are needed to ascertain that renal and cerebral NIRS can be used as a reliable tool for evaluating the effectiveness of medical treatment for hsPDA.

Adaptation and Validation of the Lithuanian Version of the Pediatric Voice Handicap Index.

OBJECTIVES: The aim of this study was to develop the Lithuanian version of the Pediatric Voice Handicap Index (pVHI) and to assess its psychometric characteristics. METHODS: The Lithuanian version of the pVHI was prepared according to the standard requirements for the questionnaire translation and adaptation procedure. It also included forward and backward translations of the original questionnaire, as well as a committee review and psychometric testing of the final version of the pVHI. A total of 126 children between 4 and 13 years of age were included in the study. Two study groups were formed: a group consisting of children with dysphonia (n = 70) and a control group of children without any alterations in their voice (n = 56). The questionnaire was always completed by their parents. The results were statistically analysed to assess the reliability, validity, sensitivity and specificity of the Lithuanian version of the pVHI. RESULTS: High internal consistency of the Lithuanian version of the pVHI was determined (Cronbach's α = 0.938). The test-retest analysis also showed a high correlation between the two tests (r = 0.949) for both the dysphonic and control groups. The mean overall pVHI score was significantly higher (P < 0.001) in the dysphonic group than in the control group: 26.16 ± 11.84 and 2.43 ± 2.61, respectively. Similar results were obtained for all domains of pVHI. The most sensitive and specific limiting value for discrimination between the clinical and control groups was the sum of 8 points. CONCLUSIONS: The Lithuanian version of the pVHI is a reliable and valid instrument for the evaluation of the Voice Handicap Index in the pediatric population and can be easily applied in daily clinical practice.

Connective tissue graft vs porcine collagen matrix after immediate implant placement in esthetic area: A randomized clinical trial.

BACKGROUND: The use of connective tissue graft (CTG) with immediate implant placement and provisionalisation have shown promising results. It is not clear if the same outcome could be achieved using porcine-derived collagen matrix (PDCM) as grafting material. OBJECTIVES: This study aimed to assess the esthetic and functional outcomes of immediate temporization of immediately placed fully tapered implants combined with bone and soft tissue augmentation, using either a CTG or a PDCM, in fresh extraction sockets of the anterior sites. MATERIALS AND METHODS: Patients with a failing anterior tooth were included in this study. After extraction, they received an immediate implant with simultaneous hard and soft tissue augmentation and immediate provisional restoration. Patients were randomly assigned to one of the group. Soft tissue augmentation in the control group (CTG) consisted of a CTG, whereas PDCM was used in the test group. After 4 months, definitive restorations were delivered, and pink esthetic score (PES) was evaluated at T1, prosthetic delivery, and at 12-month follow-up (T2). In addition, crestal bone change, probing depth, bleeding on probing, plaque index, bleeding on provisional removal, and implant stability quotient were also recorded. RESULTS: A total of 45 patients received the intended treatment (22 controls and 23 tests) 45 implants totally, with no implant failures at T2. PES mean ± SD after 1 year was noted to be 12.9 ± 1.2 for the CTG group and 12.1 ± 1.3 for the PDCM group (p = 0.507). CONCLUSION: Within the limits of this trial, both treatment protocols resulted in comparable esthetic outcomes, with results showing PES >12 and stable clinical parameters after 1 year of follow-up.

Outcomes and Risk Factors of Critically Ill Patients with Hematological Malignancy. Prospective Single-Centre Observational Study.

Background and Objectives: Oncohematological patients have a high risk of mortality when they need treatment in an intensive care unit (ICU). The aim of our study is to analyze the outcomes of oncohemathological patients admitted to the ICU and their risk factors. Materials and Methods: A prospective single-center observational study was performed with 114 patients from July 2017 to December 2019. Inclusion criteria were transfer to an ICU, hematological malignancy, age >18 years, a central line or arterial line inserted or planned to be inserted, and a signed informed consent form. Univariate and multivariable logistic regression models were used to evaluate the potential risk factors for ICU mortality. Results: ICU mortality was 44.74%. Invasive mechanical ventilation in ICU was used for 55.26% of the patients, and vasoactive drugs were used for 77.19% of patients. Factors independently associated with it were qSOFA score ≥2, increase of SOFA score over the first 48 h, mechanical ventilation on the first day in ICU, need for colistin therapy, lower arterial pH on arrival to ICU. Cut-off value of the noradrenaline dose associated with ICU mortality was 0.21 µg/kg/min with a ROC of 0.9686 (95% CI 0.93-1.00, p < 0.0001). Conclusions: Mortality of oncohematological patients in the ICU is high and it is associated with progression of organ dysfunction over the first 48 h in ICU, invasive mechanical ventilation and need for relatively low dose of noradrenaline. Despite our findings, we do not recommend making decisions regarding treatment limitations for patients who have reached cut-off dose of noradrenaline.

Venetoclax-based salvage therapy followed by Venetoclax and DLI maintenance vs. FLAG-Ida for relapsed or refractory acute myeloid leukemia after allogeneic stem cell transplantation.

We retrospectively compared the outcomes of 20 patients receiving Venetoclax + low-dose Cytarabine + Actinomycin D (ACTIVE) with 29 patients receiving FLAG-Ida as salvage therapy for relapsed or refractory AML (R/R AML) after alloSCT. The groups were statistically balanced according to age, performance status, cytogenetics, and previous treatment. The overall response rate (CR + CRp + MLFS) of ACTIVE was 75% (15/20) in comparison to 66% (19/29) in the FLAG-Ida group (p = 0.542). The cumulative CR + CRp rate was significantly higher in the ACTIVE group compared to FLAG-Ida (70% (14/20) vs. 34% (10/29), respectively, p = 0.02). All three patients failing previous Venetoclax therapy and five out of seven patients with previous FLAG-Ida exposure achieved a CR/CRp after ACTIVE induction. ACTIVE patients survived longer compared to FLAG-Ida patients (13.1 vs. 5.1 months, respectively, p = 0.032). The treatment-related mortality was 0% in the ACTIVE group and 34% (10/29) in the FLAG-Ida patients (p = 0.003). The cumulative incidence of relapse did not differ between the two treatment groups. ACTIVE appears to have comparable antileukemic activity and lower toxicity compared to FLAG-Ida resulting in improved survival. Patients with Venetoclax or FLAG-Ida exposure responded to ACTIVE.

Follow-Up Analysis of Pulmonary Function, Exercise Capacity, Radiological Changes, and Quality of Life Two Months after Recovery from SARS-CoV-2 Pneumonia.

Background and objective: According to the World Health Organization (WHO), more than 100 million people have already recovered from SARS-CoV-2 infection. Therefore, it is imperative to understand the possible outcomes of COVID-19. The aim of our study was to evaluate pulmonary function, exercise capacity, residual radiological changes, and health-related quality of life (HRQoL) at follow-up in a cohort of SARS-CoV-2 pneumonia survivors. Materials and Methods: Patients with SARS-CoV-2 infection and radiologically confirmed lung injury, with no chronic lung disease prior to this infection, were included in the study. Patients' evaluation 2 months after their discharge from hospital included spirometry (FVC, FEV1, FEV1/FVC), determination of lung volume (TLC, VC, RV) and diffusing capacity of lung for carbon monoxide (DLCO, adjusted for hemoglobin), 6-Minute Walk Test (6MWT), chest CT scan, and 36-Item Short Form General Health Survey (SF-36). Results: Fifty-one patients (25 men, 26 women) were included. The mean age was 56 years (SD-11,72). Eighteen patients (35.3%) had experienced moderate COVID-19, 21 (41.2%) severe COVID-19, and 12 (23.5%) were critically ill. The mean follow-up visit time after the discharge from hospital was 60 days (SD-17). Pulmonary function at follow-up was impaired in 24 (47.2%) patients. Reduced lung volume was observed in 15 (29.4%) patients, DLCO reduction in 15 (29.4%) patients, and only one patient displayed obstruction. Twelve patients out of 51 (12/51, 27.3%) showed reduced physical capacity in the 6 MWT, and 3/51 (9.1%) showed desaturation, with SO2 < 90%. Different levels of abnormality were found in 49/51 (96,1%) patients on follow-up chest CT; the median radiological score was 10.9 (SD ± 8.87, possible maximal score, 25). Ground-glass opacity was the most common radiological feature, found in 45 (88.2%) patients. The SF-36 scores demonstrated a reduction in health status across all domains, with the lowest scores for limitations in social activities because of physical problems, vitality, and general health. Conclusion: In the group of COVID-19 pneumonia survivors 2 months after hospital discharge, residual changes in the lungs on chest CT and in lung function and reduced physical and HRQoL status were found in a significant number of patients. To evaluate COVID-19 long-term consequences, a longer follow-up period is needed.

Mitigating arrhythmia risk in Hydroxychloroquine and Azithromycin treated COVID-19 patients using arrhythmia risk management plan.

AIMS: To assess cardiac safety in COVID-19 patients treated with the combination of Hydroxychloroquine and Azithromycin using arrhythmia risk management plan. METHODS AND RESULTS: We retrospectively examined arrhythmia safety of treatment with Hydroxychloroquine and Azithromycin in the setting of pre-defined arrhythmia risk management plan. The data was analyzed using R statistical package version 4.0.0. A two-tailed p-value<0.05 was considered significant. 81 patients were included from March 23rd to May 10th 2020. The median age was 59 years, 58.0% were female. The majority of the study population (82.7%) had comorbidities, 98.8% had radiological signs of pneumonia. Fourteen patients (17.3%) experienced QTc ≥ 480 ms and 16 patients (19.8%) had an increase of QTc ≥ 60 ms. Seven patients (8.6%) had QTc prolongation of ≥ 500 ms. The treatment was discontinued in 4 patients (4.9%). None of the patients developed ventricular tachycardia. The risk factors significantly associated with QTc ≥ 500 ms were hypokalemia (p = 0.032) and use of diuretics during the treatment (p = 0.020). Three patients (3.7%) died, the cause of death was bacterial superinfection with septic shock in two patients, and disseminated intravascular coagulation with multiple organ failure in one patient. None of these deaths were associated with cardiac arrhythmias. CONCLUSION: We recorded a low incidence of QTc prolongation ≥ 500 ms and no ventricular tachycardia events in COVID-19 patients treated with Hydroxychloroquine and Azithromycin using cardiac arrhythmia risk management plan.

Outcomes of relapsed or refractory acute myeloid leukemia patients failing venetoclax-based salvage therapies.

OBJECTIVES AND METHODS: We conducted a retrospective analysis to evaluate the outcomes of 28 heavily pretreated (median 3 (2-6) treatment lines, sixteen (57%) allotransplanted) relapsed/refractory acute myeloid leukemia patients who had failed salvage venetoclax-based therapies. RESULTS: The median age was 59 years (20-80), 20 patients (71%) had ECOG 2-4 status, and 18 patients (64%) were stratified to European Leukemia Network 2017 adverse risk group. The most common mutations were ASXL1 (21%), RUNX1 (18%), FLT3 ITD/TKD (18%), PTPN11 (15%), NRAS/KRAS (15%), and WT1 (15%). Twenty-two patients (79%) received different post-venetoclax salvage therapies with the overall response rate of 23% (complete remission + morphological leukemia-free state). Three of six (50%) patients achieved complete remissions after therapy with venetoclax + actinomycin D ± low-dose cytarabine. The remaining 6 patients did not receive any further salvage treatment mainly due to poor general condition. The median overall survival was 3.9 months for all patients (4.3 for those receiving post-venetoclax salvage vs 1.3 months receiving palliative care alone, P < .001). CONCLUSIONS: Though the remission rate and survival of patients failing venetoclax are poor, a small proportion of these R/R AML patients may still respond to cautious intensification of chemotherapy with venetoclax.

Dose Intensive Rituximab and High-Dose Methylprednisolone in Elderly or Unfit Patients with Relapsed Chronic Lymphocytic Leukemia.

Background and Objectives: BTK and BCL2 inhibitors have changed the treatment paradigms of high-risk and elderly patients with chronic lymphocytic leukemia (CLL), but their long-term efficacy and toxicity are still unknown and the costs are considerable. Our previous data showed that Rituximab (Rtx) and high-dose methylprednisolone (HDMP) can be an effective and safe treatment option for relapsed high-risk CLL patients. Materials and Methods: We explored the efficacy and safety of a higher Rtx dose in combination with a shorter (3-day) schedule of HDMP in relapsed elderly or unfit CLL patients. Results: Twenty-five patients were included in the phase-two, single-arm trial. The median progression free survival (PFS) was 11 months (range 10-12). Median OS was 68 (range 47-89) months. Adverse events (AE) were mainly grade I-II° (77%) and no deaths occurred during the treatment period. Conclusions: 3-day HDMP and Rtx was associated with clinically meaningful improvement in most patients. The median PFS in 3-day and 5-day HDMP studies was similar and the toxicity of the 3-day HDMP schedule proved to be lower. The HDMP and Rtx combination can still be applied in some relapsed high-risk and elderly or unfit CLL patients if new targeted therapies are contraindicated or unavailable. (ClinicalTrials.gov identifier: NCT01576588).

Down-regulation of miRNA-148a and miRNA-625-3p in colorectal cancer is associated with tumor budding.

BACKGROUND: MiRNAs are often deregulated in colorectal cancer and might function as tumor suppressors or as oncogenes. They participate in controlling key signaling pathways involved in proliferation, invasion and apoptosis and may serve as prognostic and predictive markers. In this study we aimed to evaluate the role of miRNA-148a and miRNA-625-3p in metastatic colorectal cancer. METHODS: Fifty-four patients with a first-time diagnosed CRC receiving FOLFOX ± Bevacizumab were involved in the study. Tumor samples underwent routine pathology examination including evaluation for tumor budding and KRAS. MiRNA-148a and miRNA-625-3p expression analysis was done by RT-PCR. Associations between expression of both miRNAs and clinico-pathological factors, treatment outcomes and survival were analyzed. RESULTS: Both miRNA-148a and miRNA-625-3p were down-regulated in the tumors compared to normal colonic mucosa. Significantly lower expression of both miRNAs was noticed in tumors with budding phenomenon compared to tumors without it (median values of miRNA-148a were 0.314 and 0.753 respectively, p = 0.011, and 0.404 and 0.620 respectively for miRNA-625-3p, p = 0.036). Significantly lower expression of miRNA-625-3p was detected in rectal tumors, compared to tumors in the colon (median 0.390 and 0.665 respectively, p = 0.037). Progression free survival was significantly lower in patients with high miRNA-148a expression (6 and 9 months respectively, p = 0.033), but there were no significant differences in PFS for miRNA-625-3p and in overall survival for both miRNAs. CONCLUSIONS: There was a significant relationship between low miRNA-148a and miRNA-625-3p expression and tumor budding, which is thought to represent epithelial-mesenchymal transition. Both studied miRNAs may be associated with a more aggressive phenotype and could be the potential prognostic and predictive biomarkers in CRC. Further investigation is needed to confirm miRNAs involvement in EMT, and their prognostic and predictive value.

Preoperative long-course chemoradiotherapy plus adjuvant chemotherapy versus short-course radiotherapy without adjuvant chemotherapy both with delayed surgery for stage II-III resectable rectal cancer: 5-Year survival data of a randomized controlled trial.

BACKGROUND AND OBJECTIVE: At present, there are common recommendations for treatment for stage II-III resectable rectal cancer patients: preoperative conventional chemoradiotherapy (CRT) with delayed surgery in 6-8 weeks or preoperative short-course radiotherapy (SCRT) followed by immediate surgery. The aim of this study was to compare overall survival (OS) and disease-free survival (DFS) in two treatment groups: preoperative SCRT and CRT both with delayed surgery plus adjuvant chemotherapy in CRT arm. MATERIALS AND METHODS: A total of 150 patients were randomly assigned to two groups: 75 to CRT (preoperative conventional CRT, 50Gy/25 fr with fluorouracil and leucovorin on the 1st and the 5th week of RT followed by TME surgery in 6-8 weeks and 4 cycles of adjuvant fluorouracil/leucovorin every 4 weeks; then follow-up) and 75 to SCRT (preoperative short-course RT, 25Gy/5 fr followed by TME surgery in 6-8 weeks; then follow-up). The data of 140 patients (72 in CRT and 68 in SCRT group) were included in statistical analysis. Primary end points were OS and DFS. RESULTS: Median follow-up was 60.5 (range, 5-108) months. The 5-year DFS was 67% in the CRT group (n=72) and 45% in the SCRT group (n=68) (P=0.013; HR=1.88; 95% CI, 1.13-3.12; P=0.015). The 5-year OS was 79% and 62% in the CRT and SCRT groups, respectively (P=0.015; HR=2.05; 95% CI, 1.13-3.70; P=0.017). The 5-year OS for intent-to-treat (ITT) population (n=150) was 78% in the CRT and 58% in the SCRT group (P=0.003; HR=2.28; 95% CI, 1.30-4.00; P=0.004). CONCLUSIONS: The 5-year DFS and OS were significantly better in the CRT than the SCRT group. For ITT population, OS was also significantly better after CRT versus SCRT.

Chronic myeloid leukemia incidence, survival and accessibility of tyrosine kinase inhibitors: a report from population-based Lithuanian haematological disease registry 2000-2013.

BACKGROUND: Currently available chronic myeloid leukaemia (CML) survival reports have originated from more affluent countries. Herein we report the entire country data on incidence and survival of CML, as well as penetrance of tyrosine kinase inhibitors (TKIs) in Lithuania. METHODS: We analyzed all patients (N = 601) from the national haematological disease monitoring system who were diagnosed with CML between 2000 and 2013. Crude (CR) and age-standardized (weighted) (ASW(R)) incidence and mortality rates, as well as 1-, 5-, and 10-year relative survival rates (RSR) were calculated. Information on TKI penetration is also reported. RESULTS: Throughout the entire 2000-2013 period the median age at diagnosis of CML patients was 62 years. The respective incidence and mortality CRs were 1.28 and 0.78, both characterized by decreasing trends over the observation period. A 5-year RSR increased from 0.33 [95 % CI, 0.27-0.40] in 2000-2004 to 0.55 [95 % CI, 0.47-0.63] in 2005-2009. However, the respective 5-year RSRs for patients aged 65-74 and ≥75 were only 0.33 [95 % CI, 0.24-0.42] and 0.18 [95 % CI 0.07-0.23] during the entire study period. TKI penetrance for CML patients grew from 1.5 % in 2000-2004 to 30.6 % in 2005-2009 and 69.1 % in 2010-2013. TKI penetrance was low in the older age groups (60 % for the 65-74 and 19 % for the ≥75 patient group, in 2010-2013). CONCLUSION: Relative CML survival in Lithuania steadily improved and paralleled the increase in TKI treatment availability. Patients above 64 years rarely received TKIs and their relative survival remained low throughout the observation period. The latency of TKI availability may have influenced the survival trends.

Malnutrition assessed by phase angle determines outcomes in low-risk cardiac surgery patients.

BACKGROUND & AIMS: Phase angle (PA), which is obtained from bioelectrical impedance analysis (BIA), is a non-invasive method for measuring altered electrical properties of biological tissues. It has been recognised as an objective prognostic marker of disease severity and frailty. The aim of this study is to determine whether PA is a marker of malnutrition and postoperative morbidity in low operative risk patients undergoing cardiac surgery. METHODS: A prospective study was conducted in a tertiary hospital. The nutritional state of the cardiac surgery patients was evaluated using BIA the day before the scheduled surgery. After applying selection criteria, 342 low operative risk patients were selected and classified into two groups in accordance with the PA value: a low PA group and a normal PA group. The correlation between low PA and low fat-free mass index (FFMI), a marker of malnutrition, was assessed. Associations between low PA and adverse postoperative outcomes, defined by the Society of Thoracic Surgeons postoperative risk evaluation model, were analysed. The impact of low PA on length of stay in an ICU and hospital was evaluated. RESULTS: Low PA was detected in 61 (17.8%) patients in the selected group, which consisted of low operative risk patients with a median Euroscore II value of 1.46 (IQR: 0.97-2.03) and was associated with FFMI with Pearson's R of 0.515 (p < 0.001). Low PA was associated with higher rates (13 [21.3%] vs. 30 [10.7%] p = 0.023) and risk of postoperative morbidity in univariate regression analysis (OR = 2.27, Cl 95% = 1.10-4.66, p = 0.026). Furthermore, low PA persisted as an independent factor in multivariate regression analysis (OR = 2.50, CI 95% 1.18-5.29, p = 0.016) adjusted for preoperative risk factors of postoperative morbidity. Evaluation of hospitalisation length revealed a tendency of a prolonged hospitalisation (>14 days) rate (31 [50.8%] vs. 105 [37.8%], p = 0.063) in the group with low PA. CONCLUSION: A low preoperative PA is an indicator of malnutrition and determines adverse outcomes after cardiac surgery. Further research is needed to evaluate clinical applications of the PA, such as a more accurate identification of malnourished cardiac surgery patients.