Beta blockers (BBs) are a cornerstone for patients with heart failure (HF) and ventricular dysfunction. However, their use in patients recovering from a cardiogenic shock (CS) remains a bone of contention, especially regarding whether and when to reintroduce this class of drugs. FRENSHOCK is a prospective multicenter registry including 772 CS patients from 49 centers. Our aim was to compare outcomes (1-month and 1-year all-cause mortality) between CS patients taking and those not taking BBs in three scenarios: (1) at 24 h after CS; (2) patients who did or did not discontinue BBs within 24 h; and (3) patients who did or did not undergo the early introduction of BBs. Among the 693 CS included, at 24 h after the CS event, 95 patients (13.7%) were taking BB, while 598 (86.3%) were not. Between the groups, there were no differences in terms of major comorbidities or initial CS triggers. Patients receiving BBs at 24 h presented a trend toward reduced all-cause mortality both at 1 month (aHR = 0.61, 95% CI 0.34 to 1.1, p = 0.10) and 1 year, which was, in both cases, not significant. Compared with patients who discontinued BBs at 24 h, patients who did not discontinue BBs showed lower 1-month mortality (aHR = 0.43, 95% CI 0.2 to 0.92, p = 0.03) and a trend to lower 1-year mortality. No reduction in outcomes was observed in patients who underwent an early introduction of BB therapy. BBs are drugs of first choice in patients with HF and should also be considered early in patients with CS. In contrast, the discontinuation of BB therapy resulted in increased 1-month all-cause mortality and a trend toward increased 1-year all-cause mortality.

Lymphoma is the most frequent hematological malignancy with wide disease spectrum of watchful waiting period, active treatment, survivorship, and palliative care. All these steps impose unmet needs in terms of prevention, symptom alleviation, or prognosis. Complementary and integrative medicine (CIM) is widely used by patients with lymphoma to cope with such issues. Here, we describe the different CIM modalities that may be effective and safe for the management of patients with lymphoma. Low inflammatory diet and ginseng seem effective for lymphoma prevention. Pain and neuropathy may be improved using acupuncture, touch therapy and specific dietary supplements. Nausea/vomiting, fatigue, and insomnia may be relieved by acupuncture, mind-body, touch therapy, and certain dietary supplements. Vitamin D, curcumin, and some traditional medicine herbs may positively impact lymphoma prognosis. Finally, safety issues should be considered especially for the concomitant use of dietary supplements and lymphoma-directed therapies. CIM may be beneficial along the continuum of lymphoma management although safety concerns should be considered when used concomitantly with conventional therapy.

Introduction: Based on the results of the phase 1b (NCT02203773) and phase 3 (VIALE-A; NCT02993523) studies, venetoclax (VEN) in combination with hypomethylating agents (HMAs) was approved by FDA and EMA for the treatment of patients (pts) with newly diagnosed (ND) acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy (IC) or whose age is 75 years or more. In particular, in the VIALE-A trial the association Ven+Azacitidine (AZA) has proven to induce rapid and durable remissions, with a median overall survival (OS) of 14.7 vs 9.6 months of pts enrolled in the placebo+Aza arm. The GIMEMA 2320 Trial (NCT04589728) is a prospective, observational study intended to investigate the outcome of pts treated with the combination Ven+HMA, in a real-world setting. Methods: Pts not candidate to IC because of age (≥75 years), performance status (PS) or comorbidities according to the SIE/SIES/GITMO (Ferrara) criteria, were eligible to the AML2320 trial and to receive the combination HMA plus venetoclax. VEN (400 mg a day, orally, day 1-28), AZA (75 mg/m 2 a day, day 1-7) and Decitabine (DEC) (20 mg/m 2 a day, day 1-5) were given at conventional doses during a 28-day cycle. Evaluation of OS was the primary end-point of the trial; response rate, time to response, event free survival (EFS), disease free survival (DFS), cumulative incidence of relapse (CIR), and safety profile were secondary end-points. Results: From November 2020 to December 2021, 188 pts were enrolled to the observational trial with 178 being evaluable at the time of this analysis. Ninety-six (54%) males and 82 (46%) females; median age 74 years (49-85) with 74 (42%) pts being 75 years old or more. One-hundred and 20 (68%) pts had “ de novo” AML and 58 (32%) secondary AML. In pts below the age of 75 years, reasons that contraindicated exposure to IC were: pulmonary diseases (6%), active infections poorly controlled with antibiotic therapy (5%); cardiac ejection fraction < 50% (4.5%), ECOG PS ≥ 3 not related to the underlying AML (4%); psychiatric illnesses requiring specific therapy (3%). In 54% of the pts below the age of 75, there was also a miscellanea of other conditions which physicians recognized as incompatible with IC. ELN2017 risk-category assignment was feasible in 151 pts with 34 (23%), 69 (46%) and 48 (32%) belonging to the favorable, intermediate and adverse category, respectively. One-hundred and 34 (75%) pts received VEN+AZA and 44 (25%) VEN+DEC. The median no. of delivered courses was 5 (1-27). Eleven (6%) pts were submitted to an allogeneic stem cell transplant after having received 4 courses of VEN+HMA and being in CR/CRi. After the first course, response assessment was evaluated in 123/178 (69%) pts with 70 (57%) being in CR/CRi. One-hundred and 53 pts were given a second course, and response assessment was available in 73; at this stage, 47/73 (64%) were in CR/CRi. With a median follow-up of 19.9 months, the median OS for the whole population is 14.2 months (12.4-18.4) (Figure 1A) and the median DFS 13.7 months (10-NR) (Figure 1B). One- and 2-year OS is 58% (51%-67%) and 33% (26%-43%), respectively; 1- and 2-year DFS is 53% (42%-67%) and 44% (33%-59%), respectively. No significant differences were found in OS and DFS when the survival analysis was split by age (< or ≥ 75 years). Median OS for favorable-, intermediate- and adverse-risk category was 24.5 months (14.2-NR), 15.4 months (11.9-NR) and 8.9 months (6.8-13.4), respectively. Median DFS for favorable-, intermediate- and adverse-risk category was NR (10.8-NR), 14.1 months (8-NR) and 9.9 months (3.2-NR), respectively. Conclusions: To our knowledge this is one of the largest series of pts with AML treated with VEN+HMA in a real-world setting. With all the limitations of a data collection still to implement, we reported for this Italian cohort of pts a median OS that is similar to that observed in the VIALE-A study (14.2 vs 14.7 months); also, our median follow-up is similar to the one of the VIALE-A study, at the time of its publication (19.9 vs 20.5 months). This real-life experience confirms that the combination VEN+HMA is an effective treatment for a very difficult to treat population of pts. This analysis also denotes the need for educational activities intended to sensitize physicians towards a more appropriate and timely evaluation of response; indeed, a sizeable proportion of Italian hematologists still approach assessment of response to VEN+HMA the same way they did when using HMA alone.

Atrial fibrillation (AF) is an increasingly recognized comorbidity in patients with cancer. Indeed, cancer patients have a significantly higher incidence of AF than that observed in the general population. A reciprocal relationship between these two diseases has been observed, as much as some assume AF to be a marker for occult cancer screening, especially in older adults. The pathophysiological mechanisms are many and varied, including the underlying pro-inflammatory state, specific treatments (chemo- and radiotherapy), and surgery. The therapeutic management of patients with cancer and AF involves the same rhythm and frequency control strategies as the general population; however, the numerous interactions with chemotherapeutics, which lead to a significant increase in side effects, as well as the extreme fragility of the patient, should be considered. Anticoagulant therapy is also a complex challenge to address, as bleeding and stroke risk scores have not been fully assessed in this subpopulation. Furthermore, in large studies establishing the efficacy of direct oral anticoagulants (DOACs), cancer patients have been underrepresented. In this review, we elaborate on the mechanisms linking AF to cancer patients with a particular focus on the therapeutic challenges in this population.

This study aims to describe the functional status of a cohort of subacute COVID-19 patients treated in a dedicated rehabilitation unit and to compare functional outcomes between patients previously hospitalized in the intensive care unit (ICU group) and patients assisted in the medical care unit (MCU group). Clinical and functional evaluations were performed at admission and discharge. The functional status was assessed using Barthel index (BI), functional ambulation categories (FAC), trunk control test (TCT), and dysphagia outcome and severity score (DOSS). All patients received multidisciplinary tailored rehabilitation. We evaluated 171 patients (with a mean age of 67.7 ± 11.9 years, 117 were males), 110 coming from the ICU (with a mean age of 63.24 ± 10.9 years), and 61 coming from the MCU (with a mean age of 75.75 ± 9.09 years). The ICU group showed a worse functional status at admission compared with the MCU group [BI 2.5 (0-20) vs. 20 (10-60), FAC 0 (0-0) vs. 0 (0-2), TCT 61 (42-100) vs. 100 (61-100), DOSS 5 (1-7) vs. 7 (7-7)] and had significantly longer hospital stay. At discharge, all functional scales were improved with no statistically significant differences between the two groups. Early rehabilitation of COVID-19 survivors improves functional recovery closing the initial gap between the ICU and MCU groups. In addition, it is effective to improve the functional outcome reducing the costs for longer-term assistance of COVID-19 patients.

Abstract ESC 2022 Guidelines suggest that low-risk patients receiving anthracyclines and/or anti-HER2 therapies can be followed within the oncology program with appropriate referral to cardio-oncology if cancer therapy-related cardiovascular toxicity or new or uncontrolled cardiovascular risks emerges. ACE-I or ARB and beta-blockers should not be considered for primary prevention. Design The SAFE trial is a four-arm, randomized, phase 3, double-blind, placebo-controlled, national multicentric study conducted at eight oncology departments in Italy. Between July 2015 and June 2020 patients with breast cancer were recruited and considered eligible for trial inclusion if they had indicated primary or postoperative systemic therapy using an anthracycline-based regimen. Patients with a prior diagnosis of cardiovascular disease or high-risk features were excluded. Cardioprotective therapy (bisoprolol (B), ramipril (R), or both drugs, as compared to placebo (P)) was administered for 1 year since the initiation of chemotherapy or until the end of trastuzumab therapy in the case of HER2 positive patients. All drugs were systematically titrated, up to the target daily dose of B (5 mg, OD), R (5 mg, OD), and P, if tolerated. The primary endpoint was defined as the detection of any subclinical impairment (worsening ≥10%) in left ventricular ejection fraction measured with 3-dimensional echocardiography (3DLVEF), and in global longitudinal strain (GLS) at the end-of-therapy (EOT) and at 2-year follow-up (EOF). Results 262 women (median age, 48 years; range, 24-75 years) were enrolled and treated. We analyzed 222 patients who had completed the pre-planned cardiological assessment at 24 months. Baseline demographic, tumor and cardiovascular profiles were similar between groups. All patients received anthracyclines, 215 at least three cycles (range 1-6), 217 patients also received taxane, and 77 adjuvant trastuzumab. Forty-nine patients were treated with neoadjuvant chemotherapy, 154 had adjuvant endocrine therapy, and 124 had postoperative radiation therapy. 3DLVEF and GLS data are reported in the Table as means±SE (95% CI). Statistical analysis was performed by ANCOVA. The percent changes from the baseline are reported in the Figure. At EOF GLS worsened by 10% or greater in 65 % of patients enrolled in the P arm, in 13%, 9%, and 10% of patients enrolled in the R, B, and R+B arms, respectively (P < 0.05). A reduction of 10% or greater in 3DLVEF was observed in 49% in the P arm, 4% in the R arm, 2% in the B arm, and 5% in the R+B arm (P < 0.05). Study drugs were well tolerated with no serious adverse events, the R+B arm showed significantly more side effects and had a significantly higher rate of allocated treatment discontinuation/reduction as compared to the other arms. Conclusion The results of the SAFE trial suggest that primary prevention should be considered also in low-risk breast cancer receiving anthracyclines and/or anti-HER2 therapies.TableFigure

Abstract Background Lowering low-density lipoprotein cholesterol (LDL-C) is the cornerstone of cardiovascular disease prevention, especially after the occurrence of a major adverse cardiac and cerebrovascular event (MACCE). Collection of epidemiological data is crucial for monitoring healthcare appropriateness and the fulfillment of guidelines recommendations. Purpose This analysis aimed to evaluate the proportion of high-risk patients who achieved LDL-C goal as suggested by the international guidelines by analyzing regional administrative data and to explore the predictors of therapeutic failure, with a focus on the role of gender. Methods By linking health administrative and laboratory data, we collected data from seven Local Health Districts on residents aged ≥45 years. Inclusion criteria were: 1) at least one LDL-C measurement in the year; 2) a history of MACCE (defined as myocardial infarction and/or stroke and/or revascularization of the coronary, carotid, or peripheral arteries) and/or type 2 diabetes mellitus (T2DM). Cohorts were defined at 1st January 2019 and 1st January 2020. Lipid lowering therapy use (defined as ≥2 prescription fillings or ≥75% coverage of treatment days) over the past 6 months if LDL-C data were available or over the past year if no LDL-C data were available was monitored. The outcome was the number of patients with on-treatment LDL-C optimal levels, as defined by levels <55 mg/dl for patients with MACCE and <70 mg/dl for patients with T2DM without MACCE. Results A cohort of 174,200 individuals was analyzed (55% males). As regards subjects on lipid-lowering therapies, we found that female gender was associated with a significantly lower probability to have LDL-C levels at target (OR: 0.58±0.01; p<0.0001) in patients with MACCE with or without T2DM, in a model adjusted for age, district area, and the presence of cardiovascular risk factors and comorbidities (renal failure, heart failure, atrial fibrillation). This result was confirmed also in the analysis conducted in subjects without lipid-lowering therapies (OR: 0.56±0.01; p<0.0001). No significant differences were documented by stratifying for the presence of clinical pathways aimed to the active call of the patients by clinicians ("Initiative Health"). Conclusions These results demonstrated that females have a significantly lower probability to reach LDL-C levels recommended targets. This datum is confirmed even in the absence of lipid-lowering therapies. These results call for action aimed to: 1) education for general population and for patients with MACCE with a specific target on females; 2) information for clinicians for the need of assessing adequate lipid-lowering therapy prescription and adherence irrespectively of gender; 3) organization of clinical pathways - from admission to recovery and follow-up - with a specific focus on secondary prevention target attainment.