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Introduction: High sensitivity troponin T (hsTnT) is a strong predictor of adverse outcome during SARS-CoV-2 infection. However, its determinants remain partially unknown. We aimed to assess the relationship between severity of inflammatory response/coagulation abnormalities and hsTnT in Coronavirus Disease 2019 (COVID-19). We then explored the relevance of these pathways in defining mortality and complications risk and the potential effects of the treatments to attenuate such risk.Methods: In this single-center, prospective, observational study we enrolled 266 consecutive patients hospitalized for SARS-CoV-2 pneumonia. Primary endpoint was in-hospital COVID-19 mortality. Results: hsTnT, even after adjustment for confounders, was associated with mortality. D-dimer and CRP presented stronger associations with hsTnT than PaO2. Changes of hsTnT, D-dimer and CRP were related but only D-dimer was associated with mortality. Moreover, low molecular weight heparin showed attenuation of the mortality in the whole population, particularly in subjects with higher hsTnT.Conclusions: D-dimer possessed a strong relationship with hsTnT and mortality. Anticoagulation treatment showed greater benefits with regard to mortality. These findings suggest a major role of SARS-CoV-2 coagulopathy in hsTnT elevation and its related mortality in COVID-19. A better understanding of the mechanisms related to COVID-19 might pave the way to therapy tailoring in these high-risk individuals.

Exercise Doppler echocardiography (EDE) is a well-validated tool in ischemic and valvular heart diseases. However, its use in the assessment of the right heart and pulmonary circulation unit (RH-PCU) is limited. The aim of this study is to assess the semi-recumbent bicycle EDE feasibility for the evaluation of RH-PCU in a large multi-center population, from healthy individuals and elite athletes to patients with overt or at risk of developing pulmonary hypertension (PH). From January 2019 to July 2019, 954 subjects [mean age 54.2 ± 16.4years, range 16–96, 430 women] underwent standardized semi-recumbent bicycle EDE with an incremental workload of 25 watts every 2min, were prospectively enrolled among 7 centers participating to the RIGHT Heart International NETwork (RIGHT-NET). EDE parameters of right heart structure, function and pressures were obtained according to current recommendations. Right ventricular (RV) function at peak exercise was feasible in 903/940 (96%) by tricuspid annular plane systolic excursion (TAPSE), 667/751 (89%) by tissue Doppler-derived tricuspid lateral annular systolic velocity (S′) and 445/672 (66.2%) by right ventricular fractional area change (RVFAC). RV—right atrial pressure gradient [RV–RA gradient = 4 × tricuspid regurgitation velocity2 (TRV)] was feasible in 894/954 patients (93.7%) at rest and in 816/954 (85.5%) at peak exercise. The feasibility rate in estimating pulmonary artery pressure improved to more than 95%, if both TRV and/or right ventricular outflow tract acceleration time (RVOT AcT) were considered. In high specialized echocardiography laboratories semi-recumbent bicycle EDE is a feasible tool for the assessment of the RH-PCU pressure and function.

ObjectiveTo investigate the role of alcohol as a causal factor for intracerebral hemorrhage (ICH) and whether its effects might vary according to the pathogenic mechanisms underlying cerebral bleeding.MethodsWe performed a case-control analysis, comparing a cohort of consecutive white patients with ICH aged 55 years and older with a group of age- and sex-matched stroke-free controls, enrolled in the setting of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) between 2002 and 2014. Participants were dichotomized into excessive drinkers (>45 g of alcohol) and light to moderate drinkers or nondrinkers. To isolate the unconfounded effect of alcohol on ICH, we used causal directed acyclic graphs and the back-door criterion to select a minimal sufficient adjustment set(s) of variables for multivariable analyses. Analyses were performed on the whole group as well as separately for lobar and deep ICH.ResultsWe analyzed 3,173 patients (1,471 lobar ICH and 1,702 deep ICH) and 3,155 controls. After adjusting for the preselected variables in the minimal sufficient adjustments, heavy alcohol intake was associated with deep ICH risk (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.36–2.09) as well as with the overall risk of ICH (OR, 1.38; 95% CI, 1.17–1.63), whereas no effect was found for lobar ICH (OR, 1.01; 95% CI, 0.77–1.32).ConclusionsIn white people aged 55 years and older, high alcohol intake might exert a causal effect on ICH, with a prominent role in the vascular pathologies underlying deep ICH.

The objective of this study was to verify the adherence of Italian family physicians and neurologists to the Guidelines on Diagnosis of Dementia of the Italian Society of Neurology. A multicentre survey was carried out, in 72 neurological centres. The centres included at least 15 consecutive subjects suspected of having a dementia. The adherence of family physicians to the guidelines was poor. Neurologists performed a complete neuropsychological evaluation in a minority of the cases. Patients who had a decrease of Mini Mental Status Examination scores after six months higher than or equal to 4 were more represented among those patients for whom one or more recommendations were not respected. In Italy the adherence to the Guidelines on Diagnosis of Dementia and AlzheimerValidation studys Disease of the Italian Society of Neurology is very poor for family physicians (GPs) and satisfactory, albeit improvable, on the part of neurologists. Respect for the guidelines might improve the outcome of patients with dementia.

Non-alcoholic fatty liver disease (NAFLD) is a growing epidemic that encompasses three distinct clinical phenotypes: uncomplicated fatty liver, non-alcoholic steato-hepatitis (NASH) and NASH-related cirrhosis with its complications, including hepatocellular carcinoma. To date, no pharmacological treatments have been approved and lifestyle modifications including reduced caloric intake targeting a 7-10% weight loss from baseline assessment represent the standard approach. Mediterranean Diet has been recommended as the best dietary pattern since it is easy to follow and, independently of caloric intake its nutritional components have beneficial metabolic effects that not only improve steatosis but also risk factors for cardio-vascular events, the leading cause of morbidity/mortality in individuals with NAFLD. Other dietary patterns such as low carbohydrates ketogenic diet and Dietary Approach to Stop Hypertension (DASH) diet can be used in patients with NAFLD. Recently, intermittent fasting diets have gained popularity among healthy individuals and have been proposed as a safe and effective treatment for the metabolic syndrome in experimental and in a few human studies. In this narrative review, we aim to summarize the evidence for the available dietary approaches for patients with NAFLD.

Background Ruxolitinib (Ruxo), an orally bioavailable and selective inhibitor of JAK1 and JAK2, significantly reduces splenomegaly and disease-related symptoms in patients with myelofibrosis (MF). However, no clear survival benefit has been demonstrated, which may in part reflect suboptimal drug exposure related to lower dosages needed to minimize hematological toxicity, specifically cytopenias. Furthermore, the optimal management of specific conditions such as leukocytosis or thrombocytosis in patients under ruxolitinib therapy is still undefined. In these cases, combining ruxolitinib with a cytoreductive agent like hydroxyurea (HU) might improve hematological response. Aims: To evaluate the efficacy and safety of Ruxo and HU combination. Methods This observational multicenter study, conducted from April 2012 to April 2017, enrolled 20 adult patients with a confirmed diagnosis of primary myelofibrosis (PMF), post-polycythemia vera (PPV-MF), or post-essential thrombocythemia (PET-MF) with hyperproliferative manifestations of the disease not controlled by Ruxo therapy. All patients we enrolled into the study had received Ruxo at a starting dose based on baseline platelet count. Patients were included into the study when Ruxo proved to be unable to reduce WBC and/or platelet count to within normal range (WBC Results The addition of HU was started after a median time of ruxolitinib monotherapy of 6.5 months (range 1-49.6 months): 17 patients (85%) started HU treatment due to lack of WBC control, whereas the remaining 3 patients (15%) started for the lack of platelet control. While on Ruxo monotherapy, ten patients (50%) needed a dose reduction due to hematological toxicity and three patients temporarily discontinued Ruxo due to severe thrombocytopenia (15%). After 14.5 months (range 2-195) median time of combination therapy in 8 patients the Ruxo daily doses increased (mean increase = 5.1 mg BID), in 9 the dose was unchanged despite the addition of HU, and only in three cases the ruxolitinib dose had to be reduced (mean reduction = 3.4 mg BID). Overall, the mean daily dose of Ruxo administered to the whole cohort of patients increased by 1.8 mg BID (P=.013), and only one patient had to discontinue Ruxo, due to severe thrombocytopenia. Non-hematological adverse events were not observed. Among the 17 patients who started combination therapy to control WBC count, 14 (82.3%) obtained a WBC response, whereas, among the three patients who started HU in association with Ruxo in order to reduce platelets count, two (66.6%) achieved a platelet response. In addition, 12 patients of the whole study cohort had clinical improvement in MF-associated symptomatic burden, with 9 of them showing spleen and symptoms response and the remaining three only spleen response. Thus, a clinical response of any type was obtained in 8 patients (40%) during Ruxo monotherapy and in 17 patients (85%) during Ruxo-HU combination (P=.003). Of note, all 8 patients in which Ruxo dose was increased during combination had at least one type of drug-related clinical response. Conclusion In conclusion, the combination of HU with Ruxo yielded a high clinical response rate and increased Ruxo exposure in patients with hyperproliferative forms of MF. The association was very well tolerated, and the hematological toxicities mostly and were generally manageable with dose reductions and/or supportive treatment. Disclosures Pane: AMGEN: Speakers Bureau; Novartis: Research Funding, Speakers Bureau; BMS: Speakers Bureau.

BACKGROUND: After ruxolitinib discontinuation, the outcome of patients with myelofibrosis (MF) is poor with scarce therapeutic possibilities. METHODS: The authors performed a subanalysis of an observational, retrospective study (RUX-MF) that included 703 MF patients treated with ruxolitinib to investigate 1) the frequency and reasons for ruxolitinib rechallenge, 2) its therapeutic effects, and 3) its impact on overall survival. RESULTS: A total of 219 patients (31.2%) discontinued ruxolitinib for ≥14 days and survived for ≥30 days. In 60 patients (27.4%), ruxolitinib was rechallenged for ≥14 days (RUX-again patients), whereas 159 patients (72.6%) discontinued it permanently (RUX-stop patients). The baseline characteristics of the 2 cohorts were comparable, but discontinuation due to a lack/loss of spleen response was lower in RUX-again patients (P =.004). In comparison with the disease status at the first ruxolitinib stop, at its restart, there was a significant increase in patients with large splenomegaly (P 10 mg twice daily predicted better spleen (P =.05) and symptom improvements (P =.02), the reasons for/duration of ruxolitinib discontinuation and the use of other therapies before rechallenge were not associated with rechallenge efficacy. At 1 and 2 years, 33.3% and 48.3% of RUX-again patients, respectively, had permanently discontinued ruxolitinib. The median overall survival was 27.9 months, and it was significantly longer for RUX-again patients (P =.004). CONCLUSIONS: Ruxolitinib rechallenge was mainly used in intolerant patients; there were clinical improvements and a possible survival advantage in many cases, but there was a substantial rate of permanent discontinuation. Ruxolitinib rechallenge should be balanced against newer therapeutic possibilities.

PurposeThis study was a quality-control study of resting and exercise Doppler echocardiography (EDE) variables measured by 19 echocardiography laboratories with proven experience participating in the RIGHT Heart International NETwork.MethodsAll participating investigators reported the requested variables from ten randomly selected exercise stress tests. Intraclass correlation coefficients (ICC) were calculated to evaluate the inter-observer agreement with the core laboratory. Inter-observer variability of resting and peak exercise tricuspid regurgitation velocity (TRV), right ventricular outflow tract acceleration time (RVOT Act), tricuspid annular plane systolic excursion (TAPSE), tissue Doppler tricuspid lateral annular systolic velocity (S’), right ventricular fractional area change (RV FAC), left ventricular outflow tract velocity time integral (LVOT VTI), mitral inflow pulsed wave Doppler velocity (E), diastolic mitral annular velocity by TDI (e’) and left ventricular ejection fraction (LVEF) were measured.ResultsThe accuracy of 19 investigators for all variables ranged from 99.7 to 100%. ICC was > 0.90 for all observers. Inter-observer variability for resting and exercise variables was for TRV = 3.8 to 2.4%, E = 5.7 to 8.3%, e’ = 6 to 6.5%, RVOT Act = 9.7 to 12, LVOT VTI = 7.4 to 9.6%, S’ = 2.9 to 2.9% and TAPSE = 5.3 to 8%. Moderate inter-observer variability was found for resting and peak exercise RV FAC (15 to 16%). LVEF revealed lower resting and peak exercise variability of 7.6 and 9%.ConclusionsWhen performed in expert centers EDE is a reproducible tool for the assessment of the right heart and the pulmonary circulation.

Introduction Serum uric acid (SUA) has been depicted as a contributory causal factor in metabolic syndrome (MS), which in turn, portends unfavourable prognosis. Aim We assessed the prognostic role of SUA in patients with and without MS. Methods We used data from the multicentre Uric Acid Right for Heart Health study and considered cardiovascular mortality (CVM) as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. Results A total of 9589 subjects (median age 58.5 years, 45% males) were included in the analysis, and 5100 (53%) patients had a final diagnosis of MS. After a median follow-up of 142 months, we observed 558 events. Using a previously validated cardiovascular SUA cut-off to predict CVM (> 5.1 mg/dL in women and 5.6 mg/dL in men), elevated SUA levels were significantly associated to a worse outcome in patients with and without MS (all p p = 0.004). Cox regression analyses identified an independent association between SUA and CVM (Hazard Ratio: 1.79 [95% CI, 1.15–2.79]; p p Conclusion Increasing SUA levels are associated with a higher CVM risk irrespective of the presence of MS: a cardiovascular SUA threshold may improve risk stratification. Graphic abstract

Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare variant of HL that accounts for 5% of all HL cases. The expression of CD20 on neoplastic lymphocytes provides a suitable target for novel treatments based on Rituximab. Due to its rarity, consolidated and widely accepted treatment guidelines are still lacking for this disease. Methods: Between 1 December 2007 and 28 February 2018, sixteen consecutive newly diagnosed adult patients with NLPHL received Rituximab (induction ± maintenance)-based therapy, according to the baseline risk of German Hodgkin Study Group prognostic score system. The treatment efficacy and safety of the Rituximab-group were compared to those of a historical cohort of 12 patients with NLPHL who received Doxorubicin, Bleomycin, Vinblastine, Dacarbazine (ABVD) chemotherapy followed by radiotherapy (RT), if needed, according to a similar baseline risk. The primary outcome was progression-free survival (PFS) and secondary outcomes were overall survival (OS) and side-effects (according to the Common Terminology Criteria for Adverse Events, v4.03). Results: After a 7-year follow-up (range, 1–11 years), PFS was 100% for patients treated with the Rituximab-containing regimen versus 66% for patients of the historical cohort (p = 0.036). Four patients in the latter group showed insufficient response to therapy. The PFS for early favorable and early unfavorable NLPHLs was similar between treatment groups, while a better PFS was recorded for advanced-stages treated with the Rituximab-containing regimen. The OS was similar for the two treatment groups. Short- and long-term side-effects were more frequently observed in the historical cohort. Grade ≥3 neutropenia was more frequent in the historical cohort compared with the Rituximab-group (58.3% vs. 18.7%, respectively, p = 0.03). Long-term non-hematological toxicities were observed more frequently in the historical cohort. Conclusion: Our results confirm the value of Rituximab in NLPHL therapy and show that Rituximab (single-agent) induction and maintenance in a limited-stage, or Rituximab with ABVD only in the presence of risk factors, give excellent results while sparing cytotoxic agent- and/or RT-related damage. Furthermore, Rituximab inclusion in advanced-stage therapeutic strategy seems to improve PFS compared to conventional chemo-radiotherapy.

To compare FDG-PET/unenhanced MRI and FDG-PET/diagnostic CT in detecting infiltration in patients with newly diagnosed Hodgkin lymphoma (HL). The endpoint was equivalence between PET/MRI and PET/CT in correctly defining the revised Ann Arbor staging system. Seventy consecutive patients with classical-HL were prospectively investigated for nodal and extra-nodal involvement during pretreatment staging with same-day PET/CT and PET/MRI. Findings indicative of malignancy with the imaging procedures were regarded as lymphoma infiltration; in case of discrepancy, positive-biopsy and/or response to treatment were evidenced as lymphoma. Sixty of the 70 (86%) patients were evaluable having completed the staging program. Disease staging based on either PET/MRI or PET/CT was correct for 54 of the 60 patients (90% vs. 90%), with difference between proportions of 0.0 (95% CI, −9 to 9%; P=0.034 for the equivalence test). As compared with reference standard, invasion of lymph nodes was identified with PET/MRI in 100% and with PET/CT in 100%, of the spleen with PET/MRI in 66% and PET/CT in 55%, of the lung with PET/MRI in 60% and PET/CT in 100%, of the liver with PET/MRI in 67% and PET/CT in 100%, and of the bone with PET/MRI in 100% and PET/CT in 50%. The only statistically significant difference between PET/MRI and PET/CT was observed in bony infiltration detection rates. For PET/CT, iodinate contrast medium infusions’ average was 86 mL, and exposure to ionizing radiation was estimated to be 4-fold higher than PET/MRI. PET/MRI is a promising safe new alternative in the care of patients with HL. Supplementary Information The online version contains supplementary material available at 10.1007/s00277-021-04537-5.

No abstract available

Background and aims Coronavirus disease (COVID-19) is a major worldwide threat for healthy individuals as well as for patients with comorbidities, but its impact on patients with cirrhosis is currently unknown. This study aimed at evaluating the impact of COVID-19 on the clinical outcome of these patients. Methods In this multicenter retrospective study, cirrhotic patients with confirmed Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection were enrolled between 1st and 31th March 2020. Clinical and biochemical data at COVID-19 and at the last outpatient visit were obtained through review of medical records. Results Fifty cirrhotic patients with confirmed SARS-CoV-2 infection were enrolled (age 67 years, 70% men, 38% virus-related, 52% previously compensated cirrhosis). At diagnosis, 64% of patients presented fever, 42% shortness of breath/polypnea, 22% encephalopathy, 96% needed hospitalization or prolonged an ongoing one. Respiratory-support was necessary in 71%, 52% received antivirals, 80% heparin. Serum albumin significantly decreased, while bilirubin, creatinine and prothrombin time significantly increased at COVID-19 diagnosis compared to last available data. The proportion of patients with MELD≥15 increased from 13% to 26% (p=0.037), acute-on-chronic liver failure and and de novo acute liver injury occurred in 14 (28%) and 10 patients, respectively. Seventeen patients died after a median of 10 (4-13) days from COVID-19 diagnosis, with a 30-day-mortality rate of 34%. Severity of lung and liver (according to CLIF-C, CLIF-OF and MELD scores) diseases independently predicted mortality. Mortality was significantly higher in hospitalized cirrhotics with COVID-19 than in those hospitalized for bacterial infections. Conclusion COVID-19 is associated with liver function deterioration and elevated mortality in cirrhotic patients., Graphical abstract, Highlights − Fifty cirrhotic patients with SARS-CoV-2 infection were studied: 64% presented with fever, 42% shortness of breath/polypnea, 22% encephalopathy; respiratory-support was necessary in 71%. − The 30-day mortality was 34% (95% CI 23-49), higher in those patients with moderate/severe respiratory failure and in those who had a more deteriorated liver function, as indicated by the increased MELD and CLIF-OF scores at COVID-19 diagnosis. − The 30-days mortality rate was higher in cirrhotics with COVID-19 than in cirrhotics with bacterial infection and in COVID-19 patients without cirrhosis − No major adverse events related to the thromboprophylaxis with heparin given to 80% of patients and treatments used to tackle the coronavirus infection.

Despite a number of randomized trials, there is clinical equipoise whether de-escalation with the omission of radiotherapy (RT) in positron emission tomography (PET) responders is safe in early-stage Hodgkin lymphoma (HL). A comprehensive Medline and conference abstracts search was performed to identify prospective studies with the following criteria: early-stage (stage I/II) HL treated with anthracycline-based chemotherapy with PET-directed randomization to ± consolidation RT. Four studies were meta-analyzed with a total of 2267 patients (RT: n = 1136, no RT: n = 1131). Pooled analysis showed a significant progression-free survival (PFS) benefit with RT (HR = 2.08, 95% CI 1.27– 3.43 p =.004, RE). There was no statistically significant overall survival (OS) benefit with RT for all patients (HR = 0.92, 95% CI 0.37–2.30, p = 0.85), nor in favorable (HR = 0.90, p =.89) or unfavorable risk (HR = 1.01, p =.99). In early-stage PET-negative HL, consolidative RT consistently improves PFS across risk stratifications over PET-directed omission of RT, with no significant impact on OS.

Background The clinical impact of the positivity of the Deauville scale (DS) of positron emission tomography (PET) performed at the end of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) in patients with advanced Hodgkin lymphoma (HL), in terms of providing rationale to shift poor responders onto a more intensive regimen, remain to be validated by histopathology. Patients and methods This prospective trial involved patients with stage IIB/IV HL who after six ABVD cycles underwent PET (PET6) and core-needle cutting biopsy (CNCB) of 2-deoxy-2[F-18] fluoro- d -glucose (FDG)-avid lymph nodes. Patients received high-dose chemotherapy/autologous haematopoietic stem cell rescue (HDCT/AHSCR) if CNCB was positive for HL, alternatively, if CNCB or PET was negative, received observation or consolidation radiotherapy (cRT) on residual nodal masses, as initially planned. The end-point was 5-year progression-free survival (PFS). Results In all, 43 of the 169 (25%) evaluable patients were PET6 positive (DS 4, 32; DS 5, 11). Among them, histology showed malignancy (HL) in 100% of DS 5 scores and in 12.5% of DS 4 scores. Fifteen patients with positive biopsy received HDCT/AHSCR, whereas 28 patients with negative biopsy, as well as 126 patients with negative PET6, continued the original plan (cRT, 78 patients; observation, 76 patients). The 5-year PFS in the negative PET6 group, negative biopsy group and positive biopsy group was 95.4%, 100% and 52.5%, respectively. Conclusion DS positivity of end-of-ABVD PET in advanced HL carried a certain number of CNCB-proven non-malignant FDG-uptakes. The DS 4 scores which were found to have negative histology appeared to benefit from continuing the original non-intensive therapeutic plane as indicated by the successful outcome in more than 95% of them by obtaining similar 5-year PFS to the PET6-negative group. By contrast, the DS 5 score had consistently positive histology and was associated with unsuccessful conventional therapy, promptly requiring treatment intensification or innovative therapeutic approaches.

Ruxolitinib (RUX), the first JAK1/JAK2 inhibitor approved for myelofibrosis (MF) therapy, has recently been associated with the occurrence of second primary malignancies (SPMs), mainly lymphomas and non-melanoma skin cancers (NMSCs). We analyzed the incidence, risk factors and outcome of SPMs in 700 MF patients treated with RUX in a real-world context. Median follow-up from starting RUX was 2·9years. Overall, 80 (11·4%) patients developed 87 SPMs after RUX start. NMSCs were the most common SPMs (50·6% of the cases). Multivariate analysis demonstrated that male sex [hazard ratio (HR): 2·37, 95% confidence interval (95%CI): 1·22–4·60, P=0·01] and thrombocytosis>400×109/l at RUX start (HR:1·98, 95%CI: 1·10–4·60, P=0·02) were associated with increased risk for SPMs. Risk factors for NMSC alone were male sex (HR: 3·14, 95%CI: 1·24–7·92, P=0·02) and duration of hydroxycarbamide and RUX therapy>5years (HR: 3·20, 95%CI: 1·17–8·75, P=0·02 and HR: 2·93, 95%CI: 1·39–6·17, P=0·005 respectively). In SPMs excluding NMSCs, male sex (HR: 2·41, 95%CI: 1·11–5·25, P=0·03), platelet>400×109/l (HR: 3·30, 95%CI: 1·67–6·50, P=0·001) and previous arterial thromboses (HR: 3·47, 95%CI: 1·48–8·14, P=0·004) were shown to be associated with higher risk of SPMs. While it is reassuring that no aggressive lymphoma was documented, active skin surveillance is recommended in all patients and particularly after prolonged hydroxycaramide therapy; oncological screening should be triggered by thrombocytosis and arterial thrombosis, particularly in males.

Helicobacter pylori has been proposed as a possible etiologic factor of ocular adnexa lymphoma (OAL), although with conflicting results. To assess the involvement of H. pylori in OAL, as (1) H. pylori DNA positivity on OAL specimens, and (2) prevalence of H. pylori gastric infection in patients with OAL. A systematic review of studies assessing H. pylori in patients with OAL was conducted by searching electronic databases from their inception to May 2019. Pooled positivity for H. pylori in OAL specimens detected by polymerase chain reaction, and pooled prevalence of H. pylori gastric infection, were calculated with 95% confidence interval (CI). Eleven studies with 308 patients were included. Pooled positivity for H. pylori was 16.8% in all OALs and 22.7% in MALT OAL, with high heterogeneity among studies. Pooled prevalence of H. pylori gastric infection in patients with OAL was 34.7%, with low statistical heterogeneity. In conclusion, H. pylori seems to be involved in a subset of OAL, but the heterogeneity found needs to be investigated in further studies. The prevalence of H. pylori gastric infection in patients with OAL does not seem to differ from that of the general population.

Ruxolitinib is the only commercially available JAK1/2 inhibitor approved for the treatment of myelofibrosis-related splenomegaly and symptoms. During treatment, as rare conditions, leukocytosis and/or thrombocytosis could develop and the management of these situations is not well established. We report here 53 myelofibrosis patients that received a combination of hydroxyurea and ruxolitinib because of uncontrolled myeloproliferation. Both drugs were administered outside clinical trials. At 48weeks, a significant reduction in leucocyte and platelet counts was observed (p= 0.02 and p= 0.04, respectively). Additionally, the spleen volume decreased from a median value of 10cm below the left costal margin (range, 0-10) to 6cm (range, 0-15). The rate of spleen response increased from 14% at the start of the combination to 45% after 48weeks. The safety profile of the combination was consistent with that observed with ruxolitinib single agent. These data require further confirmation in large cohorts of patients prospectively assessed.

We evaluated the impact on progression-free survival (PFS) of achieving a deep metabolic response at 2-deoxy-2[(18)F] fluoro-d-glucose positron emission tomography (FDG-PET) in patients with refractory or relapsed (R/R) classic Hodgkin lymphoma (cHL) following a new salvage regimen named Bv+Bs (brentuximab vedotin + bendamustine supercharge), from 2013 to 2017. In this real-life study, 20 consecutive patients (aged

a b s t r a c t The IC50 of TKIs is significantly increased when BCR-ABL+ K562 cell line is cultured in stroma conditioned media produced by BM mesenchymal cells. In particular, while the Imatinib IC50 in the stromal co- cultures was well above the in vivo through levels of the drug, the IC50s of second generation TKIs were still below their through levels. Moreover, we provide a formal comparison of the synergy between first and second generation TKIs with the JAK inhibitor Ruxolitinib to overcome BM stroma related TKI resistance. Taken together, our data provide a rationale for the therapeutic combination of TKIs and Ruxolitinib with the aim to eradicate primary BCR-ABL+ cells homed in BM niches.

The 1st International Symposium on Ostracoda (ISO) was held in Naples (1963). The philosophy behind this symposium and the logical outcome of what is now known as the International Research Group on Ostracoda (IRGO) are here reviewed, namely ostracodology over the last 50 years is sociologically analysed. Three different and important historic moments for the scientific achievements of this domain are recognised. The first one, between about 1963 and 1983, is related to applied research for the oil industry as well as to the great interest in the better description of the marine environment by both zoologists and palaeontologists. Another important aspect during this period was the work by researchers dealing with Palaeozoic ostracods, who had their own discussion group, IRGPO. Gradually, the merger of this latter group with those dealing with post-Palaeozoic ostracods at various meetings improved the communication between the two groups of specialists. A second period was approximately delineated between 1983 and 2003. During this time-slice, more emphasis was addressed to environmental research with topics such as the study of global events and long-term climate change. Ostracodologists profited also from the research “politics” within national and international programmes. Large international research teams emerged using new research methods. During the third period (2003–2013), communication and collaborative research reached a global dimension. Amongst the topics of research we cite the reconstruction of palaeoclimate using transfer functions, the building of large datasets of ostracod distributions for regional and intercontinental studies, and the implementation of actions that should lead to taxonomic harmonisation. Projects within which molecular biological techniques are routinely used, combined with sophisticated morphological information, expanded now in their importance. The documentation of the ostracod description improved through new techniques to visualise morphological details, which stimulated also communication between ostracodologists. Efforts of making available ostracod information through newsletters and electronic media are evoked.

Purpose The purpose of this study is to compare different normal tissue complication probability (NTCP) models for predicting heart valve dysfunction (RVD) following thoracic irradiation. Methods All patients from our institutional Hodgkin lymphoma survivors database with analyzable datasets were included (n = 90). All patients were treated with three-dimensional conformal radiotherapy with a median total dose of 32 Gy. The cardiac toxicity profile was available for each patient. Heart and lung dose-volume histograms (DVHs) were extracted and both organs were considered for Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) NTCP model fitting using maximum likelihood estimation. Bootstrap refitting was used to test the robustness of the model fit. Model performance was estimated using the area under the receiver operating characteristic curve (AUC). Results Using only heart-DVHs, parameter estimates were, for the LKB model: D50 = 32.8 Gy, n = 0.16 and m = 0.67; and for the RS model: D50 = 32.4 Gy, s = 0.99 and γ = 0.42. AUC values were 0.67 for LKB and 0.66 for RS, respectively. Similar performance was obtained for models using only lung-DVHs (LKB: D50 = 33.2 Gy, n = 0.01, m = 0.19, AUC = 0.68; RS: D50 = 24.4 Gy, s = 0.99, γ = 2.12, AUC = 0.66). Bootstrap result showed that the parameter fits for lung-LKB were extremely robust. A combined heart-lung LKB model was also tested and showed a minor improvement (AUC = 0.70). However, the best performance was obtained using the previously determined multivariate regression model including maximum heart dose with increasing risk for larger heart and smaller lung volumes (AUC = 0.82). Conclusions The risk of radiation induced valvular disease cannot be modeled using NTCP models only based on heart dose-volume distribution. A predictive model with an improved performance can be obtained but requires the inclusion of heart and lung volume terms, indicating that heart-lung interactions are apparently important for this endpoint.

Background. Our aim was to define predictors of late radiation-induced lung injury (RILI) in Hodgkin's lymphoma (HL) survivors treated with bleomycin-containing chemotherapy and radiotherapy. Material and methods. Eighty consecutive patients treated with chemotherapy and subsequent supradiaphragmatic radiation therapy for HL were retrospectively reviewed for symptoms and/or radiological signs of RILI. Median patient age was 26 years (range 14–55). Left, right, and total lung dosimetric parameters along with clinical, disease, and treatment-related characteristics were analyzed. Multivariate logistic regression analyses were performed. A receiver operator characteristic (ROC) curve analysis was performed to find possible cutoff values dividing patients into high- and low-risk groups. Results. Seven of 80 (9%) patients had lung disease at baseline. Four of 80 (5%) had toxicity after chemotherapy and before the beginning of radiotherapy. These patients were excluded from further evaluation. At a median time of 10 months (range 9–18), 9/69 patients (13%) developed lung radiological changes on computed tomography (CT) after treatment. Four of nine patients were diagnosed RTOG grade ≥ 2. On multivariate analyses, left-lung V30 (p = 0.004, OR = 1.108 95% CI 1.033–1.189) and total-lung V30 (p = 0.009, OR = 1.146 95% CI 1.035–1.270) resulted to be predictors of lung CT changes with a cutoff value of 16% and 15%, respectively. When only symptomatic RILI was considered a left-lung V30 cutoff value of 32% was estimated. Conclusion. Bleomycin and RT may cause lung injury in a small, but significant fraction of HL patients. Left-lung V30 predicts the risk of developing asymptomatic or symptomatic RILI after sequential chemo-radiotherapy.