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The metachronic onset of diffuse large B-cell lymphoma (DLBCL) after classic Hodgkin lymphoma (cHL) is a rare event affecting patients’ outcomes. However, although several studies have investigated the prognostic role of this event, little is known about a hypothetical common origin of the two different neoplastic cells. Aims: To investigate a possible relationship between DLBCL and cHL, in this retrospective study of 269 patients with newly diagnosed cHL treated at Bari University Hospital (Italy) between 2007 and 2020, we analyzed data from 4 patients (3 male and 1 female) with cHL who subsequently developed DLBCL. Methods: Gene expression profile analysis, assessed by NanoString Lymphoma Subtype Assay, was performed to identify the cell of origin in the DLBCL cases, in addition to Hans’s algorithm. Results: Using Hans’s algorithm, all DLBCL cases showed a germinal center-B-Cell subtype. The gene expression profile evaluated by the NanoString Lymphoma Subtype Assay revealed two cases of the GCB molecular subtype, while the others were unclassified. After first-line chemotherapy, 1 patient achieved complete remission, 3 were non-responders (2 died of lymphoma within 6 months, whereas the other achieved complete remission after autologous and allogeneic stem cell transplantation and is still alive). Conclusions: The origin of the second neoplastic cell in patients with DLBCL with a previous history of cHL remains controversial, although the different immunophenotypic characteristics suggest that it may mainly arise de novo in a subject with a possible individual predisposition to develop lymphoid neoplasms.

The present study aimed at giving voice to students from disadvantaged socio-economic backgrounds using a co-participatory approach. Participants were 59 adolescents (52.5% males) aged between 14 and 16 from five European countries who created ten comics to illustrate cyberbullying for a broader audience of peers. We analyzed texts and images according to four primary themes: cyberbullying episodes (types, platforms, co-occurrence with bullying), coping strategies, characters (roles, gender, and group membership), and emotions. The content analysis showed that online denigration on social media platforms was widely represented and that cyberbullying co-existed with bullying. Social strategies were frequently combined with passive and confrontational coping, up to suicide. All roles (cyberbully, cybervictim, bystander, reinforcer, defender) were portrayed among the 154 characters identified, even if victims and defenders appeared in the vignettes more often. Males, females, peers, and adults were represented in all roles. Among the 87 emotions detected, sadness was the most frequently expressed, followed by joy, surprise, anger, and fear. Emotions, mainly represented by drawings or drawings with text, were most often represented in association with cybervictims. The results are discussed in terms of their methodological and practical implications, as they emphasize the importance of valorizing young peoples’ voices in research and interventions against cyberbullying.

Human epidermal growth factor receptor 2 (HER2) positive cancers account for 15–20% of all breast tumors. Several drugs have been approved in the metastatic setting, including monoclonal antibodies, tyrosine kinase inhibitors (TKI) and, more recently, antibody-drug conjugates. Neratinib is a pan-HER, irreversible TKI with potent preclinical activity against trastuzumab-resistant breast cancer models. Based on Phase I and II clinical trials, the combination of neratinib plus capecitabine was compared to lapatinib and capecitabine, an established regimen for trastuzumab-resistant disease, in the randomized, Phase III NALA trial. In this trial, neratinib yielded increased progression-free survival, response duration and a benefit in time to intervention for CNS progression. However, there was no overall survival benefit, no increase in overall response rate and no improvement in QoL. The most frequent adverse event in the neratinib arm was diarrhea, which was manageable with prophylactic treatment with loperamide. Conclusion: Neratinib is a valuable addition to the therapeutic armamentarium to treat metastatic, HER2-positive breast cancer. The current positioning of the combination of neratinib and capecitabine based on the results of the NALA trial needs to consider the rapidly evolving scenario due to the recent introduction of new drugs, like the pure-HER2 TKI tucatinib and the antibody drug-conjugate trastuzumab-deruxtecan.

Parent-implemented language interventions have been used for children with expressive language delays, but no study has yet been carried out using this intervention for low-risk preterm children. The current study examined the effect of a parent-implemented dialogic book reading intervention, determining also whether the intervention differently impacted low-risk preterm and full-term children. Fifty 31-month-old late talkers with their parents participated, 27 late talkers constituted the intervention group, and 23 constituted the control group. The overall results indicated that more children in the intervention group showed partial or full recovery of their lexical expressive delay and acquired the ability to produce complete sentences relative to the control group. Concerning full-term late talkers, those in the intervention group showed a higher daily growth rate of total words, nouns, function words, and complete sentences, and more children began to produce complete sentences relative to those in the control group. Concerning low-risk preterm late talkers, children in the intervention group increased their ability to produce complete sentences more than those in the control group. We conclude that a parent-focused intervention may be an effective, ecological, and cost-effective program for improving expressive lexical and syntactic skills of full-term and low-risk preterm late talkers, calling for further studies in late talkers with biological vulnerabilities.

Aims To evaluate the impact of the COVID-19 pandemic on patient admissions to Italian cardiac care units (CCUs). Methods and Results We conducted a multicentre, observational, nationwide survey to collect data on admissions for acute myocardial infarction (AMI) at Italian CCUs throughout a 1 week period during the COVID-19 outbreak, compared with the equivalent week in 2019. We observed a 48.4% reduction in admissions for AMI compared with the equivalent week in 2019 (P < 0.001). The reduction was significant for both ST-segment elevation myocardial infarction [STEMI; 26.5%, 95% confidence interval (CI) 21.7–32.3; P = 0.009] and non-STEMI (NSTEMI; 65.1%, 95% CI 60.3–70.3; P < 0.001). Among STEMIs, the reduction was higher for women (41.2%; P = 0.011) than men (17.8%; P = 0.191). A similar reduction in AMI admissions was registered in North Italy (52.1%), Central Italy (59.3%), and South Italy (52.1%). The STEMI case fatality rate during the pandemic was substantially increased compared with 2019 [risk ratio (RR) = 3.3, 95% CI 1.7–6.6; P < 0.001]. A parallel increase in complications was also registered (RR = 1.8, 95% CI 1.1–2.8; P = 0.009). Conclusion Admissions for AMI were significantly reduced during the COVID-19 pandemic across Italy, with a parallel increase in fatality and complication rates. This constitutes a serious social issue, demanding attention by the scientific and healthcare communities and public regulatory agencies.

Summary Background Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19. Methods This multicentre, retrospective, cohort study included adult patients (aged ≥18 years) with diagnosis of a WHO-defined haematological malignancy admitted to 66 Italian hospitals between Feb 25 and May 18, 2020, with laboratory-confirmed and symptomatic COVID-19. Data cutoff for this analysis was June 22, 2020. The primary outcome was mortality and evaluation of potential predictive parameters of mortality. We calculated standardised mortality ratios between observed death in the study cohort and expected death by applying stratum-specific mortality rates of the Italian population with COVID-19 and an Italian cohort of 31 993 patients with haematological malignancies without COVID-19 (data up to March 1, 2019). Multivariable Cox proportional hazards model was used to identify factors associated with overall survival. This study is registered with ClinicalTrials.gov , NCT04352556 , and the prospective part of the study is ongoing. Findings We enrolled 536 patients with a median follow-up of 20 days (IQR 10–34) at data cutoff, 85 (16%) of whom were managed as outpatients. 440 (98%) of 451 hospitalised patients completed their hospital course (were either discharged alive or died). 198 (37%) of 536 patients died. When compared with the general Italian population with COVID-19, the standardised mortality ratio was 2·04 (95% CI 1·77–2·34) in our whole study cohort and 3·72 (2·86–4·64) in individuals younger than 70 years. When compared with the non-COVID-19 cohort with haematological malignancies, the standardised mortality ratio was 41·3 (38·1–44·9). Older age (hazard ratio 1·03, 95% CI 1·01–1·05); progressive disease status (2·10, 1·41–3·12); diagnosis of acute myeloid leukaemia (3·49, 1·56–7·81), indolent non-Hodgin lymphoma (2·19, 1·07–4·48), aggressive non-Hodgkin lymphoma (2·56, 1·34–4·89), or plasma cell neoplasms (2·48, 1·31–4·69), and severe or critical COVID-19 (4·08, 2·73–6·09) were associated with worse overall survival. Interpretation This study adds to the evidence that patients with haematological malignancies have worse outcomes than both the general population with COVID-19 and patients with haematological malignancies without COVID-19. The high mortality among patients with haematological malignancies hospitalised with COVID-19 highlights the need for aggressive infection prevention strategies, at least until effective vaccination or treatment strategies are available. Funding Associazione italiana contro le leucemie, linfomi e mieloma–Varese Onlus.

Background: Mitral valve prolapse (MVP) is characterized by an abnormal movement of the valvular apparatus which may affect the papillary muscles (PMs) function and structure. Aim of the study was to investigate abnormal PM signal in MVP by using cardiac magnetic resonance imaging (MRI). Methods and Results: We enrolled 47 consecutive patients with MVP evaluated by cardiac MRI. Additional groups included healthy volunteers, patients with moderate-to-severe mitral regurgitation (not caused by MVP) and patients with hypertrophic cardiomyopathy. Visual assessment of the PM signals was carried out and the signal intensity (SI) of both the antero-lateral and postero-medial PMs was normalized by that of the left ventricular (LV) parietal myocardium. Our results show that in the MVP group only, the PM signal intensity was significantly lower compared to the one of the LV parietal myocardium. This sign did not correlate with either LV late gadolinium enhancement or positive anamnesis for significant arrhythmias. Conclusions: In MVP patients only, PM signal is significantly reduced compared to LV parietal myocardium (“darker appearance”). The described findings are not clearly related to evidence of myocardial fibrosis, as assessed by MRI, and to previous occurrence of complex ventricular arrhythmias.

As indicated by the World Health Organization, preterm birth is a relevant public health issue, being one of the leading causes of death in children under five years of age. Its incidence has been increasing in most countries, with inequalities in terms of survival rates and negative outcomes around the world. Preterm birth is a critical event that affects not only child development, but also families and societies, particularly in the care and educational settings. The articles included in this Special Issue will add new considerations on prematurity, focusing on: (a) the effect of preterm birth on developmental outcomes from early life to adulthood, taking into account risk and protective factors; (b) the role of parenting and social environment; and (c) interventions that can promote the well-being of preterm children and their families.

Background: Primary refractory (PREF) follicular lymphoma (FL) has a completely different clinical course from that of FL that responds to front-line treatments. In addition to having poor responses to salvage therapies, it seems that patients with PREF are at increased risk of histological transformation (HT). The Aristotle consortium presented the opportunity of investigating the risk of HT in a very large series of cases. Thus, we investigated the risk of HT in patients with PREF FL compared with that of responding patients or in stable disease and ultimately their outcome. Methods: Six thousand three hundred thirty-nine patients from the Aristotle database were included in the analysis. These patients had a histologically confirmed grade 1, 2 or 3a FL diagnosed between 1997 and 2013. The primary end-points were the cumulative incidence (CI) of HT at the first progression or relapse and the survival after transformation. Findings.: The 5-year CI of HT among patients with PREF was 34% (95% confidence interval (CI): 27–43), whilst it was 7.1% (95% CI: 6.0–8.5) in the group of patients with partial response (PR) or stable disease (SD) (PR + SD) and 3.5% (95% CI: 3.0–4.2) in the group of patients achieving complete response (CR). The 5-year survival after relapse (SAR) was 33% (95% CI: 28–39) for the PREF group, 57% (95% CI 54–61) in patients with PR, 51% (95% CI 43–58) in the SD group after first-line therapy and 63% (95% CI: 66–72) in patients with CR after initial treatment (p-value

Polycythemia vera (PV) is a BCR-ABL1-negative myeloproliferative neoplasm (MPN) characterized by excessive proliferation of erythroid, myeloid, and megakaryocytic components in the bone marrow, mainly due to a Janus kinase 2 gene mutation (JAK2V617F). Givinostat, a histone-deacetylase inhibitor that selectively targets JAK2V617F cell growth, has demonstrated good efficacy and safety in three phase 1/2 studies in patients with PV. This manuscript focuses on the 4-year mean (2.8 year median) follow-up of an open-label, long-term study that enrolled 51 patients with PV (out of a total of 54 with MPN) who received clinical benefit from givinostat in these previous studies or on compassionate use, and who continued to receive givinostat at the last effective and tolerated dose. The primary objectives are to determine givinostat’s long-term safety and tolerability, and efficacy evaluated by the investigators according to internationally recognized response criteria. During follow-up, only 10% of PV patients reported Grade 3 treatment-related adverse events (AEs), while none had Grade 4 or 5 treatment-related AEs. The overall response rate for the duration of follow-up was always greater than 80% in patients with PV. In conclusion, givinostat demonstrated a good safety and efficacy profile in patients with PV, data supporting long-term use in this population.

Among children in the third year of life, late talkers comprise from 9% to 20%. This range seems to increase when addressing preterm children. This study examined video-recorded child spontaneous speech during parent&ndash, child book sharing as well as linguistic skills reported through the MacArthur Bates Communicative Development Inventories (MB-CDI) Short Form in 61 late talkers aged 30 months old (26 low-risk preterm, 8 females, 35 full-term, 12 females). Differences between low-risk preterm and full-term late talkers in child language measures and parental speech input were tested, as were the roles of child and parent factors on child language. Low-risk preterm and full-term late talkers showed similar speech and language skills. Similarly, no differences were found in measures of parental speech between groups. Child cognitive score, chronological age, and low-risk preterm status were positively associated with lexical diversity, rate, and composition of child speech production, whereas family history for language and/or learning disorders as well as parent measures of lexical diversity, rate, and grammatical complexity were negatively associated with the above child variables. In addition, child cognitive score and low-risk preterm status were positively associated with the MB-CDI measures of word and sentence production. Findings are discussed in terms of the need of good practices when following up on low-risk preterm children and of interventions targeting parents&rsquo, input to preterm and full-term late talkers.

Background Very preterm (VPT) children showed delays in reading, spelling and maths, but their academic achievement profile is not clearly understood. Aims VPT children were compared with children with specific learning disorders (SLD) and typically developing (TD) children on academic achievement, considering cognitive and linguistic phenotypic markers. A learning profile analysis was also performed. Methods We included 170 10-year old monolingual Italian-speaking children (37 VPT, 28 SLD, 105 TD) assessing cognitive, linguistic and academic skills. Results On academic achievements VPT children fell behind TD peers in some reading (text speed, comprehension), spelling (non-word), and math (number knowledge, written calculations and problem-solving) tasks. SLD children underperformed in all academic tasks with respect to VPT and TD peers. Concerning cognitive and linguistic phenotypic markers, compared to TD peers, VPT children showed lower scores in verbal IQ and phonological fluency, SLD children in phonological processing and rapid automatized naming. VPT children showed a higher rate of at-risk performance in reading compared to TD group, but a minor percentage of impaired profiles and comorbidity among learning areas compared to SLD group. Conclusions and implications The academic achievement profile of VPT children shows persistent delays, but it differs to that of SLD children, since delays are less widespread and severe, and differences were found in phenotypic markers and comorbidity. Follow-up programs and effective interventions are needed for VPT children.

The psychological status of cancer outpatients receiving anti-neoplastic treatment during the lockdown in a Italian non-COVID Cancer Center, was been investigated with the following aims: to measure the levels of post-traumatic stress symptoms, depression and anxiety; to compare patients with different cancer sites; to compare the anxiety and depression levels measured in this emergency period between cancer and non-cancer patients and between cancer patients before and after the emergency.The following questionnaires were used: The Hospital Anxiety and Depression Scale (HADs) and the Impact of Event Scale-Revised (IES-R).Worries regarding the COVID-19 on patients' lives, socio-demographic and clinical details were collected using a brief structured questionnaire.One-hundred seventy-eight outpatients were enrolled. We found that 55% of patients were above the cut-off for HADS general scale and 23.7% had severe level of PTSD. The 68% of patients declared that their worries have increased during the pandemic especially for women. Patients with lung cancer have higher general distress compared with patients with breast cancer and lymphoma. The non cancer sample had values significantly higher both for the IES-R scales and for HADS Depression subscale. Finally, cancer patients who experienced the health emergency showed higher levels of anxiety than those measured 2 years ago.Cancer out-patients of the present sample have severe post-traumatic stress symptoms and psychological distress, those with lung cancer are at higher risk and may need special attention. Non-oncological subjects have higher depression levels than cancer patients.

Since 2000, we have investigated 67 consecutive patients with stage I/II follicular lymphoma (FL) for the presence of BCL2/IGH rearrangements by polymerase chain reaction (PCR), real time quantitative PCR (RQ-PCR) and digital droplet PCR (ddPCR). All patients were treated with involved-field radiotherapy (IF-RT) (24-30 Gy). From 2005, patients with minimal residual disease (MRD) after IF-RT received rituximab (R) (375 mg/m2 , 4 weekly administrations). The median follow-up is 82 months (17-196). At diagnosis, 72% of patients were BCL2/IGH+. Progression-free survival (PFS) was significantly better in patients with undetectable/low levels (

The European regulatory authority has approved the combination of POM + LoDEX for patients with relapsed and refractory multiple myeloma (RRMM) who have undergone at least two prior therapies inclu...

Background Complex karyotype (CK) is a heterogeneous category with a negative impact in chronic lymphocytic leukaemia (CLL). Our group has recently reported that CK patients with major structural abnormalities (i.e. CK2) are characterised by a worse prognosis, as compared to other lesions within CK(CK1). Methods We performed a multicentre retrospective study to test whether the combination of CK subtypes with IGHV status could be a relevant prognostic and predictive tool. Results Among 522 patients 13% harboured CK2, 41% CK1 and/or U-IGHV (U-CK1) and 46% M-IGHV without any CK subtypes (M-noCK). After a median follow-up of 5.8 years, CK2 patients had the shortest TTFT (5-year TTFT 31%, 39 and 81%, p

In Canada, reproductive disorders known to affect the profitability of dairy cattle herds have been recorded by producers on a voluntary basis since 2007. Previous studies have shown the feasibility of using producer-recorded health data for genetic evaluations. Despite low heritability estimates and limited availability of phenotypic information, sufficient genetic variation has been observed for those traits to indicate that genetic progress, although slow, can be achieved. Pedigree- and genomic-based analyses were performed on producer-recorded health data of reproductive disorders, including retained placenta (RETP), metritis (METR), and cystic ovaries (CYST) using traditional BLUP and single-step genomic BLUP. Genome-wide association studies and functional analyses were carried out to unravel significant genomic regions and biological pathways, and to better understand the genetic mechanisms underlying RETP, METR, and CYST. Heritability estimates (posterior standard deviation in parentheses) were 0.02 (0.003), 0.01 (0.004), and 0.02 (0.003) for CYST, METR, and RETP, respectively. A moderate to strong genetic correlation of 0.69 (0.102) was found between METR and RETP. Averaged over all traits, sire proof reliabilities increased by approximately 11 percentage points with the incorporation of genomic data using a multiple-trait linear model. Biological pathways and associated genes underlying the studied traits were identified and will contribute to a better understanding of the biology of these 3 health disorders in dairy cattle.

To shed light onto the molecular basis of Philadelphia chromosome-positive acute lymphoblastic leukemia and to investigate the prognostic role of additional genomic lesions, we analyzed copy number aberrations using the Cytoscan HD Array in 116 newly diagnosed adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia enrolled in four different GIMEMA protocols, all based on a chemotherapy-free induction strategy. This analysis showed that patients with Philadelphia chromosome-positive acute lymphoblastic leukemia carry an average of 7.8 lesions/case, with deletions outnumbering gains (88% versus 12%). The most common deletions were those targeting IKZF1, PAX5 and CDKN2A/B, which were detected in 84%, 36% and 32% of cases, respectively. Patients carrying simultaneous deletions of IKZF1 plus CDKN2A/B and/or PAX5 had a significantly lower disease-free survival rate (24.9% versus 43.3%; P=0.026). The only IKZF1 isoform affecting prognosis was the dominant negative one (P=0.003). Analysis of copy number aberrations showed that 18% of patients harbored MEF2C deletions, which were of two types, differing in size: the longer deletions were associated with the achievement of a complete molecular remission (P=0.05) and had a favorable impact on disease-free survival (64.3% versus 32.1% at 36 months; P=0.031). These findings retained statistical significance also in multivariate analysis (P=0.057). KRAS deletions, detected in 6% of cases, were associated with the achievement of a complete molecular remission (P=0.009). These results indicate that in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia a detailed evaluation of additional deletions - including CDKN2A/B, PAX5, IKZF1, MEF2C and KRAS - has prognostic implications and should be incorporated in the design of more personalized treatment strategies.

Purpose. To describe the reliability and the limits of bursa premacularis (BPM) evaluation using a swept source optical coherence tomography (SS-OCT) device with enface and 16 mm-high definition (HD) longitudinal scans. Methods. 60 eyes of 60 subjects were enrolled and imaged with SS-OCT system (PLEX Elite 9000, Carl Zeiss Meditec Inc., Dublin, CA, USA). BPM area was measured using enface scans imported to ImageJ. HD horizontal and vertical longitudinal scans centered at the fovea were used to detect width (W) and central thickness (CT) of BPM at baseline (T0) and after 30 minutes (T30) performed by two different observers. An enhanced vitreous visualization software provided by the manufacturer of the device was used to highlight vitreous structures. Results. BPM was identifiable in 100% of eyes using both horizontal and vertical longitudinal scans. On horizontal scan, BPM was not entirely measurable in 21.7% and in 18.3% of cases at T0 and T30, respectively. On vertical scan, BPM was not entirely measurable in 75.0% and in 81.7% at T0 and T30, respectively. No statistically significant differences were found between the two different time measurements with an intraclass correlation coefficient above 70%. Median BPM area was 26.9 (Q1-Q3: 19.5-40.5) mm2. In en face imaging, the most frequent BPM shape was the boat one. Conclusion. SS-OCT is a reliable tool for a detailed quantification and mapping of BPM, and it is able to add useful details about the morphological BPM features in youth population. However, the enhanced visualization of the vitreous structures is still a challenge, also with the most forefront devices.

Although early object exploration is considered a key ability for subsequent achievements, very few studies have analyzed its development in extremely low gestational age infants (ELGA- GA

Purpose To assess the predictive value of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for disease recurrence after immunochemotherapy (R-CHT) and mediastinal irradiation (RT), using the recently published criteria of the Lugano classification to predict outcomes for patients with primary mediastinal large B-cell lymphoma. Methods and Materials Among 125 patients prospectively enrolled in the IELSG-26 study, 88 were eligible for central review of PET/CT scans after completion of RT. Responses were evaluated using the 5-point Deauville scale at the end of induction R-CHT and after consolidation RT. According to the Lugano classification, a complete metabolic response (CMR) was defined by a Deauville score (DS) ≤3. Results The CMR (DS1, -2, or -3) rate increased from 74% (65 patients) after R-CHT to 89% (78 patients) after consolidation RT. Among the 10 patients (11%) with persistently positive scans, the residual uptake after RT was slightly higher than the liver uptake in 6 patients (DS4; 7%) and markedly higher in 4 patients (DS5; 4%): these patients had a significantly poorer 5-year progression-free survival and overall survival. At a median follow-up of 60 months (range, 35-107 months), no patients with a CMR after RT have relapsed. Among the 10 patients who did not reach a CMR, 3 of the 4 patients (positive predictive value, 75%) with DS5 after RT had subsequent disease progression (within the RT volume in all cases) and died. All patients with DS4 had good outcomes without recurrence. Conclusions All the patients obtaining a CMR defined as DS ≤3 remained progression-free at 5 years, confirming the excellent negative predictive value of the Lugano classification criteria in primary mediastinal large B-cell lymphoma patients. The few patients with DS4 also had an excellent outcome, suggesting that they do not necessarily require additional therapy, because the residual 18 F-fluorodeoxyglucose uptake may not reflect persistent lymphoma.

Background. Recent studies have consistently identified the negative consequences of cyberbullying on adolescent mental health. Nevertheless, not all cybervictims are alike, and in the last few years some evidence has appeared indicating that faced with cyberbullying, victims may manifest different emotional outcomes. In this study, we explored whether cybervictim resilience fully or partially mediates the effects of cybervictimization and whether a confrontational coping strategy impacts emotional symptoms. Methods. The study was carried out with a sample of 474 high school students equally distributed between males and females. Data were collected using a questionnaire comprising four measures assessing cybervictimization, direct confrontation coping strategy, resilience and emotional symptoms. Results. Structural equation modelling indicated that the effects of cybervictimization and confrontational coping strategy on emotional symptoms were mediated by resilience, with cybervictimization showing a positive effect while direct confrontation a negative effect. Cybervictimization also showed a positive direct effect on emotional symptoms. Conclusions. These results are presented in light of their implications for designing effective interventions able to protect and promote adolescents&rsquo, psychological wellbeing.

Adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) represent a unique patient population with specific characteristics and needs. Growing evidences suggest that pediatric-inspired approaches improve the outcome in AYA. These results prompted the design of a pediatric AIEOP-BFM ALL 2000-based regimen - the GIMEMA LAL-1308 protocol - for newly diagnosed AYA (range 18-35 years) with Philadelphia negative (Ph-) ALL. The protocol included minimal residual disease (MRD) analysis at two different time-points (TP), that is, at the end of induction IA and consolidation IB, and a modulation in post-consolidation intensity according to MRD. Seventy-six patients were eligible between September 2010 and October 2014. The regimen was well tolerated, with 2.7% induction deaths and no deaths in the post-consolidation phase. The complete response (CR) rate was 92%; the 48-month overall survival (OS) and disease-free survival (DFS) were 60.3% and 60.4%. Both OS and DFS were significantly better in T-ALL than B-ALL. A molecular MRD

AIMS: To assess changes in glucose metrics and their association with psychological distress and lifestyle changes in patients with type 1 diabetes (T1D) using flash glucose monitoring (FGM) during lockdown following severe acute respiratory syndrome coronavirus 2 outbreak. MATERIALS AND METHODS: Single-centre, observational, retrospective study enrolling T1D patients who attended a remote visit on April 2020 at the Endocrinology division of the University Hospital Policlinico Consorziale, Bari, Italy. Lockdown-related changes in physical activity level and dietary habits were assessed on a semi-quantitative basis. Changes in general well-being were assessed by the General Health Questionnaire-12 items with a binary scoring system. Glucose metrics were obtained from the Libreview platform for the first 2 weeks of February 2020 (T0) and the last 2 weeks before the phone visit (T1). RESULTS: Out of 84 patients assessed for eligibility, 48 had sufficient FGM data to be included in the analysis. FGM data analysis revealed significant reductions in coefficient of variation, number of hypoglycaemic events, and time below range, while no changes were found in time in range, time above range, mean sensor glucose, and glucose management indicator. Moreover, the frequency of sweets consumption was inversely related to the occurrence of hypoglycaemic events during lockdown. CONCLUSIONS: Lockdown-related lifestyle changes, albeit unhealthy, may lead to reduction in FGM-derived measures of hypoglycaemia and glycaemic variability in patients with T1D.

The topic of fertility preservation in patients with a lymphoproliferative disease offers new aspects of debate, due to the introduction of novel chemotherapeutic regimens and small molecules in the clinical landscape. Cancer related infertility is mostly dependent on gonadotoxic treatments and fertile female patients are today addressed to the oocyte cryopreservation or to ovarian cortex fragment cryopreservation. These methods present advantages and disadvantages, which will be discussed in the present review, together with the options for male patients. The recent discovery of functional ovarian stem cells (OCSs) in woman ovarian cortex, opens new avenues offering a innovative procedure for fertility preservation through as model of regenerative medicine. Here, we review the gonadotoxic potential of “classical” chemotherapeutic treatments as well as of “novel” targeted therapies actually employed for lymphoproliferative neoplasms in young patients and revisit both the today available and future chances to preserve and restore fertility after the cancer healing.

Objective and methods In order to assess the efficacy of brentuximab vedotin (Bv) in combination with bendamustine (B) in multiple relapsed or refractory (RR) classic Hodgkin lymphoma (cHL), medical records of 47 patients treated with BvB in second relapse or beyond were reviewed. Results The median number of previous treatments was 2 (1-4). Bv was given at 1.8 mg/kg on day 1 and bendamustine at 90 mg/m2 on days 1 and 2 of a 21-day cycle. The median number of BvB cycles was 4 (2-7), and all patients were evaluable for efficacy. The CR and OR rates were 49% and 79%, respectively; 67% of responding patients and 2 in stable disease proceeded to a SCT procedure. After a median follow-up of 19 months (5-47), median PFS was 18 months (95%CI: 23-29), and the 2-year OS was 72%. Significantly longer PFS and OS were observed in patients attaining a major clinical response to treatment and in those who received consolidation with SCT. Fifteen (32%) patients experienced severe (G > 2) toxicity. The main toxicities were neutropenia (23%), gastrointestinal (10%), peripheral sensory neuropathy (11%), and infection (4%). Conclusion Our real-world results suggest that BvB is an effective third-line rescue and bridge-to-transplant regimen for RR-cHL patients.

Carfilzomib, lenalidomide, and dexamethasone (KRd) have been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) based on ASPIRE clinical trial. However, its effectiveness and safety profile in real clinical practice should be further assessed. We retrospectively evaluated 130 consecutive RRMM patients treated with KRd between December 2015 and August 2018, in 9 Hematology Departments of Rete Ematologica Pugliese (REP). The overall response rate (ORR) was 79%, with 37% complete response (CR). Treatment with KRd led to an improvement in response regardless of age, refractory disease, and number and type of previous therapies. After a median follow-up of 18 months, median PFS was 24 months and 2y-PFS was 54%. PFS was longer in patients achieving a very good partial response (VGPR) with median PFS of 32.4 months. The relapses after prior autologous transplant (ASCT) positively impact median PFS. Several baseline disease characteristics, such as III ISS scoring or elevated LDH, and prior exposure to lenalidomide were found to negatively impact PFS. Primary refractory or relapsed myeloma patients have been treated with KRd as bridge to ASCT with a great benefit. Thirty-four (83%) reached at least a partial response after KRd and 21 (61%) performed ASCT. In transplanted patients, median PFS was not reached and 2y-PFS was 100%. The treatment discontinuation rate due to adverse events (AEs) was 18%, most commonly for lenalidomide (11%). Overall, in 10% of patients, a KRd dose reduction was necessary at least once (2.5% for carfilzomib and 8% for lenalidomide). The most frequent AE was neutropenia (44%) and anemia (41%). Infections occurred in 14% of patients. Cardiovascular events occurred in 11% of patients. Elderly patients have tolerated therapy very well, without additional side effects compared to younger patients, except for cardiac impairment. Our analysis confirmed that KRd is effective in RRMM patients. It is well tolerated and applicable to the majority of patients outside clinical trials. A longer PFS was shown in patients achieving VGPR, in those lenalidomide naive and in patients relapsing after previous ASCT. Previous ASCT should not hamper the option for KRd therapy. Accordingly, KRd should be used as bridge regimen to ASCT with remarkable improvement in response and PFS rates. Further clinical studies are needed.

Background Immune-inflammatory biomarkers (IIBs) showed a prognostic relevance in patients with metastatic CRC (mCRC). We aimed at evaluating the prognostic power of a new comprehensive biomarker, the Pan-Immune-Inflammation Value (PIV), in patients with mCRC receiving first-line therapy. Methods In the present pooled-analysis, we included patients enrolled in the Valentino and TRIBE trials. PIV was calculated as: (neutrophil count × platelet count × monocyte count)/lymphocyte count. A cut-off was determined using the maximally selected rank statistics method. Generalised boosted regression (GBR), the Kaplan–Meier method and Cox hazards regression models were used for survival analyses. Results A total of 438 patients were included. Overall, 208 patients (47%) had a low-baseline PIV and 230 (53%) had a high-baseline PIV. Patients with high PIV experienced a worse PFS (HR, 1.66; 95% CI, 1.36–2.03, P P Conclusion PIV is a strong predictor of survival outcomes with better performance than other well-known IIBs in patients with mCRC treated with first-line therapy. PIV should be prospectively validated to better stratify mCRC patients undergoing first-line therapy.

Background Outcomes in patients with Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL) have improved with the use of tyrosine kinase inhibitors. Molecular remission ...

Background and Objectives: the aim of the study was to evaluate the repeatability and reproducibility of optical microangiography (OMAG)-based optical coherence tomography angiography (OCTA) in the optic nerve head (ONH) and radial peripapillary capillary (RPC) perfusion assessment of healthy eyes. Materials and Methods: in this observational study, a total of 40 healthy subjects underwent ONH evaluation, using an OMAG-based OCTA system at baseline (T0), after 30 min (T1), and after 7 days (T2). The main outcome measures were the vessel density (VD) and flux index (FI) of the RPCs, as well as peri-papillary retinal nerve fibre layer (pRNFL) thickness. The analysis was performed by two observers independently. The coefficient of repeatability (CR), within the subject coefficient of variation (CVw) and intrasession correlation coefficient (ICC), to evaluate intrasession repeatability of measurements was calculated for each observer. Results: the high intrasession and intersession repeatability and reproducibility were assessed in the two observers for all three outcome measures. Of note, the CRs for the first and the second observer were 0.011 (95% confidence interval (CI) 0.009&ndash, 0.014) and 0.016 (95% CI 0.013&ndash, 0.020) for FI, 0.016 (95% CI 0.013&ndash, 0.021) and 0.017 (95% CI 0.014&ndash, 0.021) for VD, and 2.400 (95% CI 1.948&ndash, 3.092) and 3.732 (95% CI 3.064&ndash, 4.775) for pRNFL thickness, respectively. The agreement between them was excellent for pRNFL assessment and very good for FI and VD. Conclusion: OCTA has a great potential in the accurate assessment of ONH and peri-papillary microcirculation. It allows for repeated and reproducible measurements without multiple scans-related bias, thus guaranteeing an independent operator analysis with good reproducibility and repeatability.

The success and sustainability of a breeding program incorporating genomic information is largely dependent on the accuracy of predictions. For low heritability traits, large training populations are required to achieve high accuracies of genomic estimated breeding values (GEBV). By including genotyped and nongenotyped animals simultaneously in the evaluation, the single-step genomic BLUP (ssGBLUP) approach has the potential to deliver more accurate and less biased genomic evaluations. The aim of this study was to compare the accuracy and bias of genomic predictions for various traits in Canadian Holstein cattle using ssGBLUP and multi-step genomic BLUP (msGBLUP) under different strategies, such as (1) adding genomic information of cows in the analysis, (2) testing different adjustments of the genomic relationship matrix, and (3) using a blending approach to obtain GEBV from msGBLUP. The following genomic predictions were evaluated regarding accuracy and bias: (1) GEBV estimated by ssGBLUP; (2) direct genomic value estimated by msGBLUP with polygenic effects of 5 and 20%; and (3) GEBV calculated by a blending approach of direct genomic value with estimated breeding values using polygenic effects of 5 and 20%. The effect of adding genomic information of cows in the evaluation was also assessed for each approach. When genomic information was included in the analyses, the average improvement in observed reliability of predictions was observed to be 7 and 13 percentage points for reproductive and workability traits, respectively, compared with traditional BLUP. Absolute deviation from 1 of the regression coefficient of the linear regression of de-regressed estimated breeding values on genomic predictions went from 0.19 when using traditional BLUP to 0.22 when using the msGBLUP method, and to 0.14 when using the ssGBLUP method. The use of polygenic weight of 20% in the msGBLUP slightly improved the reliability of predictions, while reducing the bias. A similar trend was observed when a blending approach was used. Adding genomic information of cows increased reliabilities, while decreasing bias of genomic predictions when using the ssGBLUP method. Differences between using a training population with cows and bulls or with only bulls for the msGBLUP method were small, likely due to the small number of cows included in the analysis. Predictions for lowly heritable traits benefit greatly from genomic information, especially when all phenotypes, pedigrees, and genotypes are used in a single-step approach.

Brentuximab vedotin (BV) shows a high overall response rate (ORR) in relapsed/refractory (R/R) Hodgkin lymphoma (HL) after autologous transplant (ASCT). The aim of this multicenter study, conducted in nine Hematology Departments of Rete Ematologica Pugliese, was to retrospectively evaluate the efficacy and safety of BV as salvage therapy and as bridge regimen to ASCT or allogeneic transplant (alloSCT) in R/R HL patients. Seventy patients received BV. Forty-five patients (64%) were treated with BV as bridge to transplant:16 (23%) patients as bridge to ASCT and 29 (41%) as bridge to alloSCT. Twenty-five patients (36%), not eligible for transplant, received BV as salvage treatment. The ORR was 59% (CR 26%). The ORR in transplant naive patients was 75% (CR 31%). In patients treated with BV as bridge to alloSCT, the ORR was 62% (CR 24%). In a multivariate analysis, the ORR was lower in refractory patients (p

Outpatient autologous stem cell transplantation (ASCT) has proven to be feasible in terms of physical morbidity and mortality outcomes, but little data exist on the impact of this procedure on quality of life (QoL). The purpose of this prospective, observational, longitudinal cohort study was to compare the effects of inpatient (n = 76) and outpatient (n = 64) modes of care on QoL in patients with multiple myeloma who underwent ASCT. Patients were treated according to their preference for the inpatient or outpatient model. QoL was assessed using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) at baseline (7 days before ASCT; T1) and at days +7 (T2) and +30 (T3) after ASCT. Overall, inpatients achieved higher mean values at each time point (86.05 ± 15.54 at T1, 89.23 ± 19.19 at T2, and 87.96 ± 13.6 at T3) compared with outpatients (85.62 ± 14.51 at T1, 87.42 ± 23.41 at T2, and 83.98 ± 20.2 at T3), although the differences did not reach statistical significance. Inpatients showed higher mean scores than outpatients in physical well-being (7.67 ± 5.7, 15.44 ± 6.34, and 12.96 ± 6.03, respectively, versus 5.89 ± 4.33, 13.92 ± 7.05, and 8.84 ± 6.33, respectively; P .05). Mean scores on social/family well-being were significantly higher in the outpatient group compared with the inpatient group (22.93 ± 13.29, 21.14 ± 5.31, and 21.64 ± 4.58, respectively, versus 20.59 ± 3.79, 19.52 ± 5.12, and 20.01 ± 3.97, respectively; P = .003). There were no significant between-group differences with respect to functional well-being and emotional status. Among adults at a single institution undergoing ASCT for MM, the use of outpatient care compared with standard transplantation care did not result in improved QoL during transplantation. Further research is needed for replication and to assess longer-term outcomes and implications.

Summary We aimed to investigate the performance of three deregression methods (VanRaden, VR; Wiggans, WG; and Garrick, GR) of cows’ and bulls’ breeding values to be used as pseudophenotypes in the genomic evaluation of test-day dairy production traits. Three scenarios were considered within each deregression method: (i) including only animals with reliability of estimated breeding value (RELEBV ) higher than the average of parent reliability (RELPA ) in the training and validation populations; (ii) including only animals with RELEBV higher than 0.50 in the training and RELEBV higher than RELPA in the validation population; and (iii) including only animals with RELEBV higher than 0.50 in both training and validation populations. Individual random regression coefficients of lactation curves were predicted using the genomic best linear unbiased prediction (GBLUP), considering either unweighted or weighted residual variances based on effective records contributions. In summary, VR and WG deregression methods seemed more appropriate for genomic prediction of test-day traits without need for weighting in the genomic analysis, unless large differences in RELEBV between training population animals exist.

Clinical trial results indicate that romidepsin, a histone deacetylase inhibitor, is a promising treatment in relapsed/refractory T-cell lymphomas (TCLs). This retrospective multicenter study was conducted in patients with relapsed/refractory TCL treated with romidepsin monotherapy through a Named Patient Program (NPP) in Italy. Principal endpoints were overall response rate (ORR), safety, and overall survival (OS). The ORR in 33 evaluable patients was 24.2% with an ORR in the cutaneous TCL of 35.7%. Global OS was 39.3% at 30 months. There were not any specific differences on hematological and extrahematological adverse events. Data from patients treated with romidepsin outside a controlled clinical trial give additional information about the clinical use, efficacy, and toxicity of the drug given to relapsed or refractory TCL patients in a real life context as TCLs are rare diseases and more information is needed. These findings suggest that romidepsin is effective and safe for heavily pretreated TCL patients.

Sensory-motor experiences are known to build up concrete and abstract concepts during the lifespan. The present study aimed to test how finger counting habits (right-hand vs. left-hand starters) could influence the spatial-numerical representation in number-to-position (explicit) and digit-string bisection (implicit) tasks. The subjects were Italian primary school children (N= 184, from the first to the fifth year) and adults (N= 42). No general preference for right- or left-starting in the finger counting was found. In the explicit task, right- or left-starting did not affect performance. In the implicit task, the right-hand starters shifted from the left to the right space when bisecting small and large numbers respectively, while the left-hand starters shifted from the right to the left space with higher leftward bias for large numbers. The finger configuration in Italian children and adults influences the spatial-numerical representation, but only when implicit number processing is required by the task.

© 2018 The Authors., [Background]: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. [Patients and Methods]: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months., [Results]: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide., [Conclusion]: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits., Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc.

Melanocortins are peptides with well-recognized antiinflammatory and neuroprotective activity. No data are currently available on melanocortin receptor-4 (MC4R) gene polymorphisms and tumors, including glioblastomas (GBMs), or their relationship with radiotherapy or chemotherapy. The aim of this study was to evaluate the possible predictive/prognostic role of the MC4R SNPs on GBM patients. Fifty-five patients with a proven diagnosis of GBM, treated with radiotherapy and temozolomide, were consecutively enrolled. MC4R gene SNPs (rs17782313, rs489693, rs8087522, rs17700633) were analyzed by a validated TaqMan® SNP genotyping assays. Univariate and multivariate analyses were performed. A P

While the poor psychosocial outcomes of young people who have experienced bullying are well known, the harm associated with experiences that do not meet the bullying criteria is not well understood. The aim of this study was to examine the level of harm associated with experiences of peer aggression, as well as bullying, by directly measuring the four elements of intent, perceived harm, repetition and power imbalance that comprise the bullying criteria. The purpose of the study was to establish whether bullying was the most harmful form of peer aggression and whether other types of peer aggression that did not comprise all elements of bullying were comparably harmful. Over 6000 students (aged 11-16) from 10 countries completed a student victimization and aggression questionnaire. Data showed that approximately 50% of participants were not intentionally harmed through peer aggression, although this varied across countries, ranging from 10% in India to 87.5% in Taiwan. In all countries, analyses identified a group that had experienced repeated peer aggression, but with no power imbalance, comparable in size to the bullied group, suggesting that bullying is just "the tip of the iceberg". Victims of bullying self-reported the greatest experiences of harm, although victims of repeated aggression reported comparable harm. The findings show that peer aggression experiences that do not meet the bullying criteria are also rated as harmful by victims. More research is needed to fully understand negative peer interactions that include behaviors outside the scope of the bullying definition, particularly with regard to repeated peer aggression. This study suggests that researchers should consider the level of harm experienced by individuals and avoid terminology such as bullying, while policy makers should place a strong and explicit focus on encompassing a broader realm of harmful peer aggression.

Background: An increasing body of research on typically and atypically developing infants has shown that motor skills play an important role in language development. To date, however, the role of specific object exploration skills for early gesture and vocabulary development has not been investigated in extremely low gestational age infants (ELGA, GA < 28 weeks), who are at greater risk for motor and language delays than full-term (FT) infants. Purpose: This longitudinal study examined relations between 6-month active exploratory behaviors and 12- month word comprehension, gestures and vocal production, controlling for cognitive performance and neonatal condition (ELGA vs FT). Methods: Forty infants, 20 ELGA and 20 FT, and their mothers participated in the study. Mother-infant play interaction was video-recorded at 6 and 12 months. Oral and manual object exploration at 6 months and spontaneous gestures and vocal production at 12 months were coded. Word comprehension was evaluated with the Italian version of the MacArthur-Bates CDI parent questionnaire at 12 months. Cognitive performance was examined with the Griffiths Mental Developmental Scales at 6 months and the Bayley-III Scales at 12 months. Results: Regression analyses showed that after accounting for cognitive performance and neonatal condition, oral exploration was related to word comprehension, and manual exploration to gestures and vocal production in the overall sample. Conclusions: Cascading effects of specific object exploration skills on gestures and language comprehension and production in preterm infants and FT infants are discussed. Clinical implications for early assessment of and interventions involving object exploration skills, which may affect language development, are considered for the preterm population.

Refined karyotype-based prognostic stratification of chronic lymphocytic leukemia with a low- and very-low-risk genetic profile

Summary Copy number aberrations (CNAs) represent cooperating events in B-lineage acute lymphoblastic leukaemia (B-ALL); however, their clinical relevance across different age cohorts is unclear. We analysed the recurrent CNAs in 157 age-stratified B-ALL negative cases for recurrent rearrangements (B-NEG ALL), and their association with patients’ clinico-biological features. We found that: (i) CDKN2A/RB1-deleted and EBF1-deleted adults had a shorter disease-free survival than those with wild-type, (ii) among the unfavourable markers, CDKN2A/RB1 deletions and K/NRAS mutations retained their impact in multivariate analysis, encouraging the evaluation of CDKN2A/RB1 deletions and RAS mutations in the diagnostic/prognostic workflow to refine ALL risk assessment.

// Thomas Sau-Yan Chan 1 , Yuh-Shan Lee 2 , Ilaria Del Giudice 3 , Marilisa Marinelli 3 , Caterina Ilari 3 , Luciana Cafforio 3 , Anna Guarini 4 , Daryl Tan 2 , Colin Phipps 2 , Yeow-Tee Goh 2 , William Hwang 2 , Allan Zhi-Kai Goh 2 , Lisa Lai-Ping Siu 5 , Saliangi Wu 6 , Chun-Yin Ha 7 , Shek-Ying Lin 8 , Chi-Hang Kwok 9 , Chi-Kuen Lau 10 , Kit-Fai Wong 5 , Robin Foa 3 , Yok-Lam Kwong 1 , Eric Tse 1 1 Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China 2 Department of Haematology, Singapore General Hospital, Outram, Singapore 3 Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy 4 Department of Molecular Medicine, Sapienza University, Rome, Italy 5 Department of Pathology, Queen Elizabeth Hospital, Hong Kong, China 6 Department of Medicine, Queen Elizabeth Hospital, Hong Kong, China 7 Department of Medicine, Tuen Mun Hospital, Hong Kong, China 8 Department of Medicine, United Christian Hospital, Hong Kong, China 9 Department of Medicine, Princess Margaret Hospital, Hong Kong, China 10 Department of Medicine, Tseung Kwan O Hospital, Hong Kong, China Correspondence to: Eric Tse, email: ewctse@hku.hk Keywords: chronic lymphocytic leukaemia, Chinese, pathological characteristics, clinical outcomes, prognostication Received: November 14, 2016 Accepted: February 13, 2017 Published: March 09, 2017 ABSTRACT Chronic lymphocytic leukaemia (CLL) is uncommon in Chinese population and its biology, genetics and treatment outcome in Chinese patients have not been comprehensively investigated. In this study, we studied the clinicopathological features and outcome of 212 Chinese patients with newly diagnosed CLL in Hong Kong and Singapore. The median age at diagnosis was 64 years. The majority of patients presented with early-stage disease (Binet stage A, 56.1%). Del(13)(q14) was the most frequent abnormality (41.7%) detected by fluorescence in situ hybridization (FISH) analysis. Del(17p) and TP53 gene mutations were detected in 7.8% and 8.2% of patients, respectively. MYD88 mutations were found at a higher frequency (11.5%) than expected. CLL with unmutated variable region of the immunoglobulin heavy chain genes ( IGHV ) occurred in only 31.2% of cases, and was associated with advanced-stage disease (p

During the past three decades, allogeneic stem cell transplant (allo-SCT) has been considered the standard of care for adult patients with high-risk acute lymphoblastic leukemia (ALL) and, given th...

Whole body low dose computed tomography (WBLDCT) is the first-choice imaging modality to identify bone involvement in multiple myeloma (MM). Because the unenhanced LDCT co-registered to positron emission tomography (PET) (LDCT/PET) has similar technical characteristics to WBLDCT, we aimed to assess its reliability in the detection of bone disease, for employing fluorine-18-fluorodeoxyglucose (Thirty three consecutive MM patients were prospectively enrolled and evaluated with WBLDCT to assess bone involvement. In addition, patients underwentThe two imaging modalities resulted highly concordant considering both patient-based (k=0.841) and region-based analysis; some discrepancies were observed in dorsal spine (k=0.809) and thorax (k=0.756). Low dose computed tomography/PET sensitivity, specificity and accuracy were 89.4%, 98.3% and 93.5%, respectively.Low dose computed tomography co-registered PET has comparable performance to WBLDCT. If confirmed on a lager sample, these encouraging results suggest the possibility to use this multimodal hybrid imaging as the only method for MM evaluation, rather than both exams, providing both morphologic and metabolic information in one session with impact on patient compliance, health care spending and especially radiation exposure.

PURPOSE To evaluate, using optical coherence tomography-angiography (OCT-A), the vascular features of good bleb function after XEN gel implantation (XGI) for uncontrolled glaucoma. METHODS Forty-three patients (43 eyes), who underwent XGI, were enrolled. According to the intraocular pressure (IOP) reduction, patients were classified into Group 1 (21 eyes; success) and Group 2 (22 eyes; failure). Optical coherence tomography-angiography (OCT-A) was performed to image the vascularization of the conjunctival bleb-wall. The main outcomes were as follows: vessel displacement areas (VDAs), major vessel displacement area (MVDA; mm2 ), non-flow whole area (NFWA; mm2 ) and bleb-wall vessel density (BVD; %). Co-registered B-scans were also considered to evaluate the bleb-wall cyst-like structure density and area (BCSD, cysts/mm2 ; BCSA, mm2 ), and the bleb-wall thickness (BT, µm). RESULTS Mean postoperative follow-up was 7.5 ± 0.14 months; Group 1 and 2 IOP were 14.0 ± 2.5 and 25.3 ± 2.1 mmHg, respectively (p

In chronic lymphocytic leukaemia (CLL), caution is warranted regarding the clinical implications of immunoglobulin variable heavy chain region (IGHV) rearrangements with a 'borderline' (BL) percentage of mutations (i.e. 97-97·9% IGHV identity). We analysed the IGHV mutational status in 759 untreated CLL patients (cohort 1). BL-CLL (n = 36, 5%) showed a time to first treatment (TFT) similar to that of M-CLL (n = 338) and significantly longer than that of UM-CLL (n = 385), despite the enrichment in subset #2 cases. In fact, CLLs belonging to subset #2 (n = 15/759, 2%) were significantly more frequent among BL-CLLs (n = 5/36, 14%), with a brief TFT. TFT of BL-CLL remained comparable to that of M-CLL also considering the 327 CLL patients evaluated at diagnosis. These findings were then validated in an independent cohort 2 of 759 newly diagnosed CLL patients (BL-CLL: n = 11, 1·4%) and in all newly diagnosed patients from cohorts 1 and 2 (n = 1 086, 84% stage A; BL-CLL: n = 47, 4·3%). BL-CLL at diagnosis showed a biological profile comparable to that of M-CLL with a low frequency of unfavourable prognostic markers, except for a significant enrichment in subset #2. Our data suggest that the prognosis of BL-CLL is good and similar to that of M-CLL, with the exception of subset #2 cases.

Background and objectives: Lymphoma patients experience a psychological and physiological decline that could be reversed by exercise. However, little is known about the effects of the exercise on psychological and physical fitness variables. Therefore, the purpose of this longitudinal study was to assess self-efficacy, fatigue and physical fitness before and after an eight-week exercise intervention. Materials and Methods: Thirty-six participants (54.4 &plusmn, 19.1 years) performed a supervised exercise program (~60 min, 2d&middot, wk&minus, 1). Each session included a combined progressive training of cardiorespiratory, resistance, flexibility and postural education exercises. Self-efficacy and fatigue were measured with the Regulatory Emotional Self-Efficacy scale and 0&ndash, 10 rating scale, respectively. Physical fitness was assessed with the body mass index, lower back flexibility, static balance, muscle strength and functional mobility. Results: Adherence to exercise was high (91.2% &plusmn, 4.8%) and no major health problems were noted in the patients over the intervention period. At baseline, significant differences were found between Hodgkin&rsquo, s lymphoma and non-Hodgkin&rsquo, s lymphoma patients by age and all dependent measures (p &lt, 0.05). Fatigue significantly decreased and the perceived capability to regulate negative affect and to express positive emotions improved after exercise (p &lt, 0.001). Significant improvements were found for body mass index, trunk lateral flexibility, monopodalic balance, isometric handgrip force and functional mobility (p &lt, 0.001). Fatigue was significantly correlated with handgrip force (r = &minus, 0.56, p &lt, 0.001) and functional mobility (r = &minus, 0.69, p &lt, 0.001). Conclusions: The supervised exercise program improved psychological and physical fitness without causing adverse effects and health problems. Therefore, exercise to improve fitness levels and reduce perceived fatigue should be considered in the management of lymphoma patients.

AIMS Peak cardiac power output-to-mass (CPOM) represents a measure of the rate at which cardiac work is delivered respect to the potential energy stored in left ventricular (LV) mass. We studied the value of CPOM and cardiopulmonary exercise test (CPET) in risk stratification of patients with heart failure (HF). MATERIALS AND RESULTS We studied 159 patients with chronic HF (mean rest LV ejection fraction 30%) undergoing CPET and exercise stress echocardiography. CPOM was calculated as the product of a constant (K = 2.22 × 10-1) with cardiac output (CO) and the mean blood pressure (MBP), divided by LV mass (M), and expressed in the unit of W/100 g: CPOM = [K × CO (L/min) × MBP (mmHg)]/LVM(g). Patients were followed-up for the primary endpoint, including all-cause death, ventricular assist device implantation, and heart transplantation, and the secondary endpoint that comprised hospitalization for HF. In multivariate Cox regression analyses, peak CPOM was selected as the most powerful independent predictor of both primary and secondary endpoint [hazard ratio (HR) 0.004, 95% confidence interval (CI) 0.004-0.3; P = 0.002 and HR 0.09, 95% CI 0.02-0.55; P = 0.009]. Sixty-month survival free from the combined endpoint was 85% in those exhibiting oxygen consumption (VO2) > 14 mL/min/kg and peak CPOM > 0.6 W/100 g. Peak VO2 ≤ 14 mL/min/kg provided incremental prognostic value over demographic and clinical variables, brain natriuretic peptide, and resting echocardiographic parameters (χ2 from 58 to 64; P = 0.04), that was further increased by peak CPOM ≤ 0.6 W/100 g (χ2 77; P

The activity and safety of a regimen combining lenalidomide with fludarabine and cyclophosphamide (FC) was investigated in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Treatment consisted of six monthly courses of the FC regimen combined with 14 days of lenalidomide given at the starting dose of 2.5 mg during course 1. The maximum tolerated dose of lenalidomide was 5 mg. Forty patients were assessed for response, 66% were IGHV unmutated, 45% showed deletion 11q or 17p. The overall response and complete remission rates were 62.5% and 22.5%, respectively, the median progression-free and overall survival (OS) were 19 and 45 months, respectively. Grade 3–4 granulocytopenia was observed in 65% of cases, severe infections in 7.5%, the lenalidomide-related toxicity was mild. In conclusion, the results of this study demonstrate that low-dose lenalidomide associated with the FC schedule is an effective treatment for R/R patients with CLL, associated with an acceptable safety profile. © 2016 Informa UK Limited, trading as Taylor & Francis Group