Infections after chimeric antigen receptor (CAR)-T-cell therapy for hematologic malignancies.

Chimeric antigen receptor (CAR)-T-cell therapies have revolutionized the management of acute lymphoblastic leukemia, non-Hodgkin lymphoma, and multiple myeloma but come at the price of unique toxicities, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and long-term "on-target off-tumor" effects. All of these factors increase infection risk in an already highly immunocompromised patient population. Indeed, infectious complications represent the key determinant of non-relapse mortality after CAR-T cells. The temporal distribution of these risk factors shapes different infection patterns early versus late post-CAR-T-cell infusion. Furthermore, due to the expression of their targets on B lineage cells at different stages of differentiation, CD19, and B-cell maturation antigen (BCMA) CAR-T cells induce distinct immune deficits that could require different prevention strategies. Infection incidence is the highest during the first month post-infusion and subsequently decreases thereafter. However, infections remain relatively common even a year after infusion. Bacterial infections predominate early after CD19, while a more equal distribution between bacterial and viral causes is seen after BCMA CAR-T-cell therapy, and fungal infections are universally rare. Cytomegalovirus (CMV) and other herpesviruses are increasingly breported, but whether routine monitoring is warranted for all, or a subgroup of patients, remains to be determined. Clinical practices vary substantially between centers, and many areas of uncertainty remain, including CMV monitoring, antibacterial and antifungal prophylaxis and duration, use of immunoglobulin replacement therapy, and timing of vaccination. Risk stratification tools are available and may help distinguish between infectious and non-infectious causes of fever post-infusion and predict severe infections. These tools need prospective validation, and their integration in clinical practice needs to be systematically studied

Prevalence of disordered eating in elite female athletes in team sports in Greece

The purpose of the study was to assess a) the prevalence of disordered eating (DE) in elite female team sports players compared to non-athletes and b) to compare DE prevalence in elite female players in basketball, volleyball and water polo. One hundred and seventy-five females were recruited (age 23.10 ± 5.4, BMI 21.85 ± 2.3 kg/m2), 53 were elite basketball players, 42 were elite volleyball players, 34 were elite water polo players and 46 were non-athletes. Participants completed the Eating Disorders Questionnaire (EDE-Q) and a physical activity questionnaire. The EDE-Q incorporates 36 statements which relate to the occurrence and frequency of key behaviours of eating disorders, under the following four subscales: Restraint, eating concern, shape concern and weight concern and a global score of disordered eating. No differences were found in the EDE-Q subscale score and global score between athletes and non-athletes. Only 6.2% of the total number of participants exhibited DE using the global score >2.3. Water polo players had significantly higher scores in the ‘eating concern’ subscale and in the frequency of key behavioural features of DE such as binge eating episodes and objective and subjective bulimic episodes, compared to volleyball and basketball players. In conclusion, team sport elite female players do not exhibit greater prevalence of DE compared to non-athletes. Water polo, a sport that emphasizes leanness and control of body weight for international distinctions, is associated with a higher tendency to exhibit DE, when compared to other team sports

Prevalence of HIV-related stigma among people with HIV in Switzerland: addressing the elephant in the room

Objectives: We aimed to determine the prevalence of HIV-related stigma among people with HIV (PWH) in Switzerland Design: A cross-sectional multicentre study nested within the Swiss HIV Cohort Study (SHCS). Methods: We included adult PWH enrolled in the SHCS, attending follow-up between March 1st, 2020, and January 31st, 2021. Inability to speak English, French, German, or Italian was the only exclusion criterion. Participants were invited to complete a validated 12-item HIV-stigma questionnaire comprising four stigma subscales (negative self-image, personalised stigma, disclosure concerns, and concerns regarding public attitudes), plus two healthcare-related stigma items. Questionnaire responses were graded using a four-point Likert-type scale, higher scores indicating higher stigma. “Non-applicable”, inferring HIV-status non-disclosure, was possible for personalised stigma; stigma scores from participants answering “non-applicable” to ≥1 items were analysed separately. Factors associated with HIV-stigma were identified through multivariable linear models. Results: Of 9643 PWH with a SHCS visit, 5563 participated in the study: 26% were female, 13% Black and 37% heterosexual; median age was 53 years (interquartile range 44–59); 2067 participants (37%) gave ≥1 “non-applicable” responses. Disclosure concerns had the highest stigma scores and were reported by 4656/5563 (84%). HIV-stigma was reported across all demographic groups. However, being female, Black, and heterosexual were independently associated with higher scores. Higher education and longer follow-up duration were associated with lower scores. Healthcare-related stigma was reported in 37% of participants. Conclusions: HIV-stigma was prevalent across all demographic groups. The association with being female and Black suggests that HIV-stigma accentuates pre-existing gender and race inequalities

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

Association between loop diuretic dose changes and outcomes in chronic heart failure: observations from the ESC-EORP Heart Failure Long-Term Registry

[Abstract] Aims. Guidelines recommend down-titration of loop diuretics (LD) once euvolaemia is achieved. In outpatients with heart failure (HF), we investigated LD dose changes in daily cardiology practice, agreement with guideline recommendations, predictors of successful LD down-titration and association between dose changes and outcomes. Methods and results. We included 8130 HF patients from the ESC-EORP Heart Failure Long-Term Registry. Among patients who had dose decreased, successful decrease was defined as the decrease not followed by death, HF hospitalization, New York Heart Association class deterioration, or subsequent increase in LD dose. Mean age was 66±13 years, 71% men, 62% HF with reduced ejection fraction, 19% HF with mid-range ejection fraction, 19% HF with preserved ejection fraction. Median [interquartile range (IQR)] LD dose was 40 (25–80) mg. LD dose was increased in 16%, decreased in 8.3% and unchanged in 76%. Median (IQR) follow-up was 372 (363–419) days. Diuretic dose increase (vs. no change) was associated with HF death [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.12–2.08; P = 0.008] and nominally with cardiovascular death (HR 1.25, 95% CI 0.96–1.63; P = 0.103). Decrease of diuretic dose (vs. no change) was associated with nominally lower HF (HR 0.59, 95% CI 0.33–1.07; P = 0.083) and cardiovascular mortality (HR 0.62 95% CI 0.38–1.00; P = 0.052). Among patients who had LD dose decreased, systolic blood pressure [odds ratio (OR) 1.11 per 10 mmHg increase, 95% CI 1.01–1.22; P = 0.032], and absence of (i) sleep apnoea (OR 0.24, 95% CI 0.09–0.69; P = 0.008), (ii) peripheral congestion (OR 0.48, 95% CI 0.29–0.80; P = 0.005), and (iii) moderate/severe mitral regurgitation (OR 0.57, 95% CI 0.37–0.87; P = 0.008) were independently associated with successful decrease. Conclusion. Diuretic dose was unchanged in 76% and decreased in 8.3% of outpatients with chronic HF. LD dose increase was associated with worse outcomes, while the LD dose decrease group showed a trend for better outcomes compared with the no-change group. Higher systolic blood pressure, and absence of (i) sleep apnoea, (ii) peripheral congestion, and (iii) moderate/severe mitral regurgitation were independently associated with successful dose decrease

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Family Business Internationalisation and Networks: Emerging Pathways

Purpose: The aim of this study is twofold: 1) to provide a meta-synthesis of the current state of knowledge in FB internationalisation research, adopting a network perspective; 2) to highlight emerging themes that may set the stage for future work on FB internationalisation, for the benefit of researchers adopting a network perspective. Methodology: In order to address the twofold purpose of the study, the current paper provides a state-of the art review of 25 peer-reviewed journal articles published from 1993 to 2014. It also presents a meta-synthesis of the theoretical approaches, key findings and concepts that were pinpointed in the review, and proposes emerging key themes that are likely set the stage for future work within this specific field. Findings: The results indicated that since the mid-1990s, research in the field from a network perspective has mainly focused on three aspects, namely: 1) the role of networks and relationships in the internationalisation process, 2) the factors that influence network formation, and 3) strategic/managerial issues in the formation and building of network ties. The current paper pinpoints emerging themes within these three aspects, and proposes future pathways. Research limitations: The review and meta-synthesis are restricted to 25 studies identified in this specific field. Originality: The study comprises an initial attempt to encompass the interface of FB internationalisation and networks

Evaluation of skis of alpine skiing behavior on the snow

Purpose: The purpose of this study was to evaluate the behavior of the skis on snow depending on sex, type of ski and the level of training of the technical skier. Material: in the research participated 57 skiers, generally of age 26 +/- 8.62 years (34 males and 23 females) at the ski center of Parnassos (Greece). The evaluation of the ski behavior on snow came up via the scores on Test 1 to Test 5 in practice, to the rating scale from 0 to 10 respectively. The participants, after performing daily training with their skis completed the questionnaire. The questionnaire included the following elements: sex, height, weight, the type of skis and the type of TEST as: 1-2) behavior of skis in long and short turning radius, respectively, 3) grip of the ski edges in turn, 4) stability of ski riding, 5) usage of general muscle strength (fatigue). Results: The correlation between the first four tests (Test 1-4) was significant at statistical significance level p < 0.05, apart from test 5, which shows reduced physical fitness of the skier. Also the majority of skiers prefer parabolic skis (carving ski), although the racing skis were highly rated. Conclusions: The widespread “carving skis” are skis with medium score in both of all five tests in comparison to the Race ski. Finally, as expected, the highest score was given by the athletes (r = 0.69-0.99). It is recommended for further research of the correct selection of the ski in relation to: the physical fitness of the skier, prevention and injuries