Prognostic Impact of Serum ß2-Microglobulin Levels in Hodgkin Lymphoma Treated with ABVD or Equivalent Regimens: A Comprehensive Analysis of 915 Patients.

The significance of serum beta-2 microglobulin (sß2m) in Hodgkin lymphoma (HL) is controversial. We analyzed 915 patients with HL, who were treated with ABVD or equivalent regimens with or without radiotherapy. Sß2m levels were measured by a radioimmunoassay (upper normal limit 2.4 mg/L). Sequential cutoffs (1.8-3.0 by 0.1 mg/L increments, 3.5 and 4.0 mg/L) were tested along with ROC analysis. The median sß2m levels were 2.20 mg/L and were elevated (>2.4 mg/L) in 383/915 patients (41.9%). Higher sß2m was associated with inferior freedom from progression (FFP) at all tested cutoffs. The best cutoff was 2.0 mg/L (10-year FFP 83% vs. 70%, p = 0.001), which performed better than the 2.4 mg/L cutoff ("normal versus high"). In multivariate analysis, sß2m > 2.0 mg/L was an independent adverse prognostic factor in the whole patient population. In multivariate overall survival analysis, sß2m levels were predictive at 2.0 mg/L cutoff in the whole patient population and in advanced stages. Similarly, sß2m > 2.0 mg/L independently predicted inferior HL-specific survival in the whole patient population. Our data suggest that higher sß2m is an independent predictor of outcome in HL but the optimal cutoff lies within the normal limits (i.e., at 2.0 mg/L) in this predominantly young patient population, performing much better than a "normal versus high" cutoff set at 2.4 mg/L.

Cognitive flexibility in autism: Evidence from young autistic children.

We examined the cognitive flexibility performance of young autistic children and a group of neurotypical peers. Thirty-six autistic children (72-83 months) and 200 age-matched typically-developing children were assessed on the Children's Color Trails Test (CCTT), a semantic and a phonemic verbal fluency task. The results showed that the autistic children performed worse than their neurotypical peers in the switching component of the CCTT. In the fluency tests, the autistic group generated overall fewer word items than their neurotypical peers, however, their poorer performance was driven by specific linguistic stimuli in the fluency tasks. The findings suggest that cognitive flexibility for the autistic children was affected in the nonverbal CCTT only, while poor performance in semantic and phonemic fluency seemed to be inherent to the language properties of the verbal fluency tasks.

Real-life Experience With Rituximab-CHOP Every 21 or 14 Days in Primary Mediastinal Large B-cell Lymphoma.

BACKGROUND/AIM: Primary mediastinal large B-cell lymphoma (PMLBCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL), whose prognosis has greatly improved since the incorporation of the anti-CD20 monoclonal antibody rituximab into current therapeutic regimens. Evidence, however, on the optimal time interval between consecutive chemoimmunotherapy (CIT) cycles is still scarce. This study aimed to evaluate the efficacy outcomes of the more commonly administered 3-weekly regimens to the biweekly ones in a PMLBCL patients' population, who were mostly treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone every 21 days (R-CHOP-21) or R-CHOP-14. PATIENTS AND METHODS: We retrospectively studied our cohort of consecutively treated PMLBCL patients, focusing on their treatment density, in order to determine possible differences in treatment outcomes. RESULTS: CIT, in the form of both R-CHOP-21 as well as R-CHOP-14 (or similar regimens), is highly active in PMLBCL, with low rates of early treatment failure. In our cohort of patients, R-CHOP-14 did not result in a meaningful improvement of freedom from progression (FFP) or overall survival (OS). CONCLUSION: Both R-CHOP-14 and R-CHOP-21 are probably equally effective in PMLBCL, yet further, prospective, randomized studies are warranted to clarify whether dose-dense regimens can be associated with better disease control and long-term results.

Serum ferritin levels in previously untreated classical Hodgkin lymphoma: correlations and prognostic significance.

Serum ferritin (SF) is frequently elevated in classical Hodgkin lymphoma (cHL). We report on its prognostic significance in an unselected series of 529 cHL patients treated with state-of-the-art therapy. Higher baseline levels correlated with markers of advanced/aggressive disease. SF levels were significantly higher in male and older patients, those with high body mass index and mixed cellularity histology. The strongest correlation was recorded between SF and complement reactive protein (CRP) levels. Gender-specific SF cutoffs which provided the best discrimination in terms of freedom from progression (FFP) were identified. In multivariate analysis elevated SF levels, advanced stage and high lactate dehydrogenase (LDH) were independent prognostic factors of inferior FFP. SF also appears to retain independent prognostic significance for progression-free survival (PFS) but not for overall survival (OS). In conclusion, SF levels in cHL reflect disease activity and are associated with adverse patient outcomes.

Reported COVID-19 Vaccination Coverage and Associated Factors among Members of Athens Medical Association: Results from a Cross-Sectional Study.

There are limited data on the prevalence and determinants of COVID-19 vaccination coverage among physicians. A cross-sectional, questionnaire-based, online study was conducted among the members of the Athens Medical Association (I.S.A.) over the period 25 February to 13 March 2021. All members of I.S.A. were invited to participate in the anonymous online survey. A structured, anonymous questionnaire was used. Overall, 1993 physicians participated in the survey. The reported vaccination coverage was 85.3%. The main reasons of no vaccination were pending vaccination appointment followed by safety concerns. Participants being informed about the COVID-19 vaccines by social media resulted in lower COVID-19 vaccination coverage than health workers being informed by other sources. Logistic regression analysis demonstrated that no fear over COVID-19 vaccination-related side effects, history of influenza vaccination for flu season 2020-2021, and the perception that the information on COVID-19 vaccination from the national public health authorities is reliable, were independent factors of reported COVID-19 vaccination coverage. Our results demonstrate a considerable improvement of the COVID-19 vaccination uptake among Greek physicians. The finding that participants reported high reliability of the information related to COVID-19 vaccination provided by the Greek public health authorities is an opportunity which should be broadly exploited by policymakers in order to combat vaccination hesitancy, and further improve COVID-19 vaccination uptake and coverage among physicians/HCWs, and the general population.

Maximum Phonation Time as a Predictor of Lactate Threshold during Intermittent Incremental Endurance Test.

The aim of the present study was to examine whether the exercise intensity corresponding to the lactate threshold may be predicted by the Maximum Phonation Time task (MPT). Ten Greek amateur football players (age: 18.4 ± 1.0 years), performed a graded cycling exercise test to exhaustion in order to determine lactate threshold. A number of physiological variables were measured including perceived exertion, cardiopulmonary values and blood lactate. The MPT variable was correlated with all of the physiological variables. Also, a binary logistic regression analysis was used to investigate whether MPT could predict lactate threshold. The ROC analysis showed specificity to be 0.90 and sensitivity to be 0.70 (optimal screening cutoff point for MPT 9.5 seconds). The results showed an odds ratio of 1.45 indicating a 45% increase in the probability of passing the threshold for every second there was a reduction in voice duration. MPT may be used as a simple, non-invasive, inexpensive method for monitoring exercise intensity during physical exercise. Further research is needed to measure its efficacy in bigger samples and in different sports.

Effectiveness of Aural-Oral Approach Based on Volubility of a Deaf Child with Late-Mapping Bilateral Cochlear Implants.

BACKGROUND: The purpose of this study was to investigate the effectiveness of aural-oral habilitation (AO) over the traditional speech-language therapy, based on the number of vocalization-volubility of a deaf child with late-mapping bilateral cochlear implants using sequential measurements. METHODS: The spontaneous productions during child interactions were analyzed. The child (CY, 7;0 years old) with a mean unaided pure-tone average (PTA) hearing loss >80 dB HL was assessed by using an assessment battery. Study design consisted of two phases: (a) baseline (end of speech therapy) and (b) end of AO treatment. Protophones were analyzed via acoustical analysis using PRAAT software. RESULTS: One-way repeated-measure ANOVAs were conducted within and between phases. The analyses revealed significant differences between the 'phase' and the vocalization outcome (F = 9.4, df = 1, p = 0.035). Post hoc analyses revealed the significant difference between the mean number of disyllable vocalizations of AO approach (p = 0.05). The mean number of vocalizations was calculated for each protophone type, but no other significant difference was measured. CONCLUSIONS: AO approach proved effective as measured through volubility. The outcome of this study is indicative and is a starting point for broader research.

The effect of endothelial Nitric Oxide Synthase G894T and T786C polymorphisms on Hypoxia-Inducible Factor-1 alpha expression in Sickle Cell Disease.

Hypoxia-Inducible Factor-1α (HIF-1α) expression is upregulated in Sickle Cell Disease (SCD) and correlates with various laboratory markers of disease severity. Nitric Oxide plays a pivotal role in SCD pathophysiology and endothelial Nitric Oxide Synthase (NOS3) polymorphisms affect prognosis and laboratory parameters. This study questions the effect of NOS3 G894T and T786C polymorphisms on HIF-1α expression in SCD. We show that G894T polymorphism is a significant predictor of HIF-1α expression. Its effect is exerted independently of hemolysis/hemoglobin fragment concentrations, as shown in multiple regression analysis. Our results establish a novel modulator of HIF-1α expression on the mRNA level and indirectly support the role of nitric oxide in the pathophysiology of SCD.

Real-life experience with the combination of polatuzumab vedotin, rituximab, and bendamustine in aggressive B-cell lymphomas.

Transplant-ineligible relapsed/refractory (rr) diffuse large B-cell lymphoma (DLBCL) patients represent an unmet medical need. Polatuzumab vedotin (Pola), an anti-CD79b antibody-drug-conjugate (ADG), with bendamustine- rituximab(BR) has recently gained approval for these patients, both in the USA and Europe, based on the GO29365 phase IIb trial. Real-life data with Pola are extremely limited. We report the outcomes of 61 Greek patients, who received Pola-(B)R mainly within a compassionate use program. Treatment was given for up to six 21-day cycles. Bendamustine was omitted in three cases due to previous short-lived responses. Fourty-nine rrDLBCL(efficacy cohort-EC) and 58 rr aggressive B-NHL (safety cohort-SC) patients received at least 1 Pola-BR cycle. Twenty-one (43%) patients of the EC responded with 12/49 (25%) CR and 9/49 (18%) PR as best response. Median progression-free survival, overall survival and duration of response were 4.0, 8.5, and 8.5 months respectively, while 55% of patients experienced a grade ≥3 adverse event, mainly hematologic. Treatment discontinuations and death during treatment were mainly due to disease progression. Twenty-two (41%) patients received further treatment; 11/22 are still alive, including one after CAR-T cells, and two after stem cell transplantation. Our data confirm that Pola-BR is a promising treatment for rrDLBCL patients, inducing an adequate response rate with acceptable toxicity. Pola-BR could be used as bridging therapy before further consolidative treatments.

Positron emission tomography after response to rituximab-CHOP in primary mediastinal large B-cell lymphoma: impact on outcomes and radiotherapy strategies.

End-of-treatment (EoT) PET/CT is used as a guide to omit radiotherapy (RT) patients with primary mediastinal large B-cell lymphoma (PMBCL). We present the mature and extended results of a retrospective study evaluating the prognostic significance of EoT-PET/CT after adequate response to R-CHOP. Among 231 consecutive PMLBCL patients, 182 underwent EoT-PET/CT and were evaluated according to the Deauville 5-point scale (D5PS) criteria. Freedom from progression (FFP) was measured from the time of PET/CT examination. Among 182 patients, 72 (40%) had D5PS score 1 (D5PSS-1), 33 (18%) had 2, 28 (15%) had 3, 29 (16%) had 4, and 20 (11%) had 5. The 5-year FFP was 97, 94, 92, 82, and 44% for D5PSS-1, D5PSS-2, D5PSS-3, D5PSS-4, and D5PSS-5, respectively. Among 105 patients with unequivocally negative PET/CT (D5PSS-1/D5PSS-2), 49 (47%) received RT (median dose 3420 cGy) and 56 (53%) did not with relapses in 0/49 vs. 4/56 patients (2 mediastinum and 2 isolated CNS relapses).The 5-year FFP for those who received RT or not was 100% versus 96%, when isolated CNS relapses were censored (p = 0.159). Among D5PSS-3 patients (27/28 irradiated-median dose 3600 cGy), the 5-year FFP was 92%. The 5-year FFP for D5PSS-4 and D5PSS-5 was 82 and 44%; 44/49 patients received RT (median dose 4000 and 4400 cGy for D5PSS-4 and D5PSS-5). Our study supports the omission of RT in a sizeable fraction of PET/CT-negative patients and definitely discourages salvage chemotherapy and ASCT in patients with PMLBCL who conventionally respond to R-CHOP, solely based on PET/CT positivity in the absence of documented progressive or multifocal disease. The persistence of positive PET/CT with D5PSS < 5 after consolidative RT should not trigger the initiation of further salvage chemotherapy in the absence of conventionally defined PD.

Montreal Cognitive Assessment in a Greek sample of patients with multiple sclerosis: A validation study.

The Montreal Cognitive Assessment (MoCA) is a brief cognitive instrument for the measurement of dementia. The aim of the present study was to measure the sensitivity of this test in a group of Greek speaking participants diagnosed with multiple sclerosis. 40 MS participants complaining for cognitive dysfunction were matched in age and education to 490 healthy participants. The MoCA test and a neuropsychological test battery were administered to both groups. The MoCA test was found to differentiate the MS from the controls (U = 3761.00, p < .001) and it was correlated with all neuropsychological tests (digit span: r = 0.454, p < .0001; phonemic verbal fluency: r = 0.390, p < .0001; semantic verbal fluency: r = 0.319, p < .0001; Color Trails Test 1 (CTT1): r = -.256, p < .0001; Color Trails Test 2 (CTT2): r = -.321, p < .0001). Multiple regression analysis showed that 10.3% of the variation in the MoCA score was accounted for by the Expanded Disability Status Scale (EDSS) total score. Also, the test showed high discriminant validity (optimal screening cut off point 25, sensitivity 0.68, specificity 0.89). MoCA is a sensitive test to differentiate cognitive impairment in Greek speaking MS participants from healthy controls. Further research is needed to use it in larger clinical samples and in different subtypes of the disease.

Evaluation of automated capillary complete blood counts for routine clinical decision making in a large cohort of hematological patients, using Mindray BC-3000 Plus Auto and Sysmex XE-5000 hematology analyzers.

INTRODUCTION: Venous blood (VB) sampling for complete blood count (CBC) via venipuncture is the basic method for the daily evaluation of hematological patients. However, several issues during this process, such as venipuncture difficulty and repetitive attempts, may cause pain, phlebitis, hematomas, inadequate sampling, and patient discomfort. Capillary blood (CB) sampling could be an alternative and less painful solution for the patient. The purpose of this study was the comparative evaluation of basic CBC parameters, as counted from venous and capillary blood samples. METHODS: During the period 06/2016-06/2019 in which the study was conducted, 1634 automated counts of VB or CB were performed, derived from 425 hematological hospitalized patients. Bland-Altman plots were performed to show the agreement of VB and CB counts of common hematological parameters (Hb, Hct, WBC, absolute neutrophil count-[ANC], RBC, Plt, MCV, MCH), using two different hematology analyzers (Mindray BC-3000 Plus Auto and Sysmex XE-5000). Clinical significance of CB sampling was assessed by applying specific clinically significant cutoffs for Hb, ANC, and Plt. RESULTS: All measured parameters revealed a significant correlation (r > .9) between CB and VB samples, irrelatively of the hematology analyzer used. CB measurements of Hb, ANC, and Plt, at different clinically important cutoff levels, showed excellent sensitivity (87%-100%), specificity (95%-100%), positive predictive value, and negative predictive value (87%-100% and 90%-100%, respectively). CONCLUSION: Capillary blood and VB counts in hematological patients were equivalent for most basic hematological parameters. Hb, ANC, and Plt CB counts revealed clinically significant performance, indicating that they can reliably substitute VB sampling in the day work.

Optimizing outcomes in relapsed/refractory Hodgkin lymphoma: a review of current and forthcoming therapeutic strategies.

The outcome of patients with relapsed/refractory classical Hodgkin lymphoma (rr-cHL) has improved considerably in recent years owing to the approval of highly active novel agents such as brentuximab vedotin and Programmed Death-1 (PD-1) inhibitors. Although no randomized trials have been conducted to provide formal proof, it is almost undisputable that the survival of these patients has been prolonged. As autologous stem-cell transplantation (SCT) remains the standard of care for second-line therapy of most patients with rr-cHL, optimization of second-line regimens with the use of brentuximab vedotin, or, in the future, checkpoint inhibitors, is promising to increase both the eligibility rate for transplant and the final outcome. The need for subsequent therapy, and especially allogeneic SCT, can be reduced with brentuximab vedotin consolidation for 1 year, while pembrolizumab is also being tested in this setting. Several other drug categories appear to be active in rr-cHL, but their development has been delayed by the appearance of brentuximab vedotin, nivolumab and pembrolizumab, which have dominated the field of rr-cHL treatment in the last 5 years. Combinations of active drugs in chemo-free approaches may further increase efficacy and hopefully reduce toxicity in rr-cHL, but are still under development.