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Among the 138 adult patients with ALCL, 64 (46%) were ALK positive, and 74 (54%) were ALK negative. Median follow-up was 8 years. At diagnosis, significantly more patients younger than 40 years old were ALK positive than ALK negative (66% v 23%, respectively; P < .001). Comparing patients with ALK-positive and ALK-negative ALCL, β(2)-microglobulin was ≥ 3 mg/L in 12% and 33% (P = .017); International Prognostic Index was high (score, 3 to 5) in 23% and 48% (P = .03); complete response rates to first-line treatment were 86% and 68% (P = .01); and 8-year overall survival (OS) rates were 82% (95% CI, 69% to 89%) and 49% (95% CI, 37% to 61%), respectively (P < .001). The survival difference mostly affected patients age ≥ 40 years. Multivariate analysis identified β(2)-microglobulin ≥ 3 mg/L (P < .001) and age ≥ 40 years (P = .029), but not ALK status, as prognostic for OS. These two variables distinguished four survival risk groups, with 8-year OS ranging from 84% to 22%. CONCLUSION Results of this long-term study enabled refinement of the prognosis of adult systemic ALCL, with ALK prognostic value dependent on age, and could provide guidance for eventual treatment adjustment.

Background Concomitant seasonal influenza vaccination with a COVID-19 vaccine booster could help to minimise potential disruption to the seasonal influenza vaccination campaign and maximise protection against both diseases among individuals at risk of severe disease and hospitalisation. This study aimed to assess the safety and immunogenicity of concomitant administration of high-dose quadrivalent influenza vaccine (QIV-HD) and a mRNA-1273 vaccine booster dose in older adults. Methods This study is an ongoing, phase 2, multicentre, open-label, descriptive trial at six clinical research sites in the USA. We describe the interim results up to 21 days after vaccination (July–August, 2021). Community-dwelling adults aged 65 years and older, who were previously vaccinated with a two-dose primary schedule of the mRNA-1273 SARS-CoV-2 vaccine, were eligible for inclusion. The second dose of the primary mRNA-1273 vaccination series was required to have been received at least 5 months before enrolment in the study. Participants were randomly assigned (1:1:1) using a permuted block method stratified by site and by age group (<75 years vs ≥75 years), to receive concomitant administration of QIV-HD and mRNA-1273 vaccine, QIV-HD alone, or mRNA-1273 vaccine alone. Randomisation lists, generated by Sanofi Pasteur biostatistics platform, were provided to study investigators for study group allocation. Unsolicited adverse events occurring immediately, solicited local and systemic reactions up to day 8, and unsolicited adverse events, serious adverse events, adverse events of special interest, and medically attended adverse events up to day 22 were reported. Haemagglutination inhibition antibody responses to influenza A/H1N1, A/H3N2, B/Yamagata, and B/Victoria strains and SARS CoV-2 binding antibody responses (SARS-CoV-2 pre-spike IgG ELISA) were assessed at day 1 and day 22. All analyses were descriptive. The study is registered with ClinicalTrials.gov , NCT04969276 . Findings Between July 16 and Aug 31, 2021, 306 participants were enrolled and randomly assigned, of whom 296 received at least one vaccine dose (100 in the coadministration group, 92 in the QIV-HD, and 104 in the mRNA-1273 group). Reactogenicity profiles were similar between the coadministration and mRNA-1273 groups, with lower reactogenicity rates in the QIV-HD group (frequency of solicited injection site reactions 86·0% [95% CI 77·6–92·1], 91·3% [84·2–96·0], and 61·8% [50·9–71·9]; frequency of solicited systemic reactions 80·0%, [70·8–87·3], 83·7% [75·1–90·2], and 49·4% [38·7–60·2], respectively). Up to day 22, unsolicited adverse events were reported for 17·0% (95% CI 10·2–25·8) of participants in the coadministration group and 14·4% (8·3–22·7) of participants in the mRNA-1273 group, and tended to be reported at a slightly lower rate (10·9% [5·3–19·1]) in participants in the QIV-HD group. Seven participants e...

L ipoprotein(a) (Lp(a)) is a recognized risk factor for coronary heart disease (CHD).1 Population studies and metaanalyses show association between Lp(a) levels and first-ever CHD events, but there is less evidence in patients with overt CHD and stable clinical symptoms. In a general population cohort (Copenhagen City Heart Study), the hazard ratio (HR) for future CHD reached a significant value of 1.9 between the 67th and 89th percentiles of Lp(a) concentration.2 Furthermore, as reported by Kamstrup et al, 3,4 risk rises most in those patients whose Lp(a) concentration is in the top decile. Causality was predicated on the basis of a strong genetic influence on the Lp(a) level through the kringle IV type 2 size polymorphism which had been shown also to associate with future myocardial infarction.2,4 In a meta-analysis of 36 prospective studies that yielded 9318 cases of nonfatal myocardial infarctions and CHD deaths, the risk ratio became significant above Lp(a) levels of ≈50 mg/dL. 5 For the 22 076 first-ever fatal or nonfatal cardiovascular disease (CVD) outcomes, the association with Lp(a) was broadly continuous but modest.6 These findings were consistent with preceding reports based on fewer studies that showed an average 1.7-fold increased risk for ischemic heart disease between the upper and lower thirds of the Lp(a) distribution. A recent very large 20-year prospective cohort study of 3467 blacks and 9851 whites showed a graded risk between Lp(a) concentration and incident CVD events which was significant only when the highest and lowest quintiles were compared with respective HRs of 1.35 and 1.27 for the 2 populations. 7 The importance of Lp(a) size polymorphisms had been appreciated for some time and summarized in a review of 36 studies that showed a doubling in CHD risk in the presence of the smaller rather than the larger isoforms (risk ratio of 2.08 for the smaller isoforms).8 By contrast, isoform size was not a predictor of future CHD events in a 12.3-year prospective study of the Framingham Offspring Cohort, although elevated Lp(a) levels were found to have independent significant associations with CHD in men but not in women.9 The © 2013 American Heart Association, Inc. Objective-Association between lipoprotein(a) (Lp(a)) level and a first-ever coronary (CHD) event is recognized. Less is evident in patients with overt CHD and stable symptoms in whom we investigated associations between Lp(a) and future events. Approach and Results-Relationships between Lp(a) concentration and CHD and cardiovascular disease outcomes during 6 years' median follow-up were evaluated in the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study. Lp(a) concentrations were measured in plasma from 7863 patients who had sustained a previous coronary event and been randomized to pravastatin or placebo. Lp(a) levels were categorized by lowest half, third quartile, 75th to 90th percentile, and highest decile. The prognostic value of Lp(a) on outcomes was assessed by fitting a Cox proportionalhazards mod...

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Brentuximab vedotin was reported to be effective and safe against refractory/relapsed Hodgkin lymphoma in cohorts of between 12 to 102 patients. Herein we report our retrospective analysis of the French experience with brentuximab vedotin used alone to treat 240 refractory/relapsed Hodgkin lymphoma patients enrolled in a named patient program between 2011 and 2013. All patients had histologically documented CD30+ Hodgkin lymphoma; 74% had refractory disease or early relapses. After a median of 3 lines of chemotherapy, brentuximab vedotin was infused intravenously (1.8 mg/kg every 3 weeks). The primary endpoint was best response. Response at the end of treatment, its duration, survival data and toxicity profile were secondary endpoints. Patients received a median of 6 cycles; 68 underwent a consolidation thereafter. The best response was observed after a median of 4 cycles in 145 (60.4%) patients: 33.8% complete response/unconfirmed complete response, 26.7% partial response. Objective responses were observed as decreased (39.3%) in the 28 patients >60 years. The median response duration was 8.4 months. With median follow-up at 16.1 months, median progression-free survival was 6.8 months and this was significantly longer for patients transplanted after brentuximab vedotin (a median of 18,8 months); median overall survival was not reached. No death has been linked to brentuximab vedotin toxicity. The most common adverse events were peripheral sensory neuropathy (29.3%) and hematological toxicity. The results of this analysis support the previously reported brentuximab vedotin efficacy with manageable toxicity. Because of the short-term responses in most patients, a high-dose therapy with stem cell transplantation for responders should be considered as quickly as possible.

The present findings suggest that the time course of the development of healthy habits depends on the time of the day and that the effect is mediated through diurnal variation in cortisol levels. Future studies are now needed to determine to what extent cortisol rhythmicity can help individuals to adopt new health behaviors. (PsycINFO Database Record