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Introduction Drug-induced thrombotic microangiopathy (DITMA) is an acquired condition resulting from exposure to a drug that induces the formation of platelet-rich thrombi in small arterioles or capillaries secondary to drug-dependent antibodies or direct tissue toxicity. Carfilzomib is a selective proteasome inhibitor approved to treat selected patients with Multiple Myeloma (MM). It is one of the drugs with the strongest evidence for a causal association with non-antibody-mediated DITMA. Case Report A 75-year-old man presented to the emergency department for the outbreak of vomit, asthenia, oliguria and dark stool emission. He was recently diagnosed with multiple myeloma, treated with lenalidomide, dexamethasone and carfilzomib. Laboratory exams were significant for microangiopathic haemolytic anaemia, thrombocytopenia and new-onset renal failure. ADAMTS-13 levels were in range, and no infectious signs were found both in blood nor in stool test. Management & Outcome A carfilzomib induced thrombotic microangiopathy was soon suspected. Thus, since daily haemodialysis and supportive care did not seem to get a fast enough recovery, the patient was treated with eculizumab with a good general outcome. Discussion Drug-induced thrombotic microangiopathy is a rare and often life-threatening acquired condition whose diagnosis can be challenging and whose therapy is not always limited to supportive treatment and drug avoidance. Carfilzomib, along with other proteasome inhibitors, is one of the described potential drugs which can trigger such a manifestation.

Introduction Injection drug use (IDU) is a known risk factor for infective endocarditis (IE) and is associated with frequent recurrences, but its prognostic impact is still debated. Moreover, the potential futility of surgery in this population is an unsolved matter. Purpose We aimed to determine the clinical characteristics, the therapeutic strategy, and the prognostic impact of injection drug use IE (IDUIE). Method We retrospectively included in the analysis 454 consecutive episodes of definite active IE admitted in a single surgical centre from January 2012 to December 2020; 14 out of them where a subsequent infective episode of the same patient. Results IDUIE cases were 63 (13.8%), without significant proportional differences over time. IDUIE patients were significantly younger (43.95±10.12 vs 67.84±13.33, p 0.00) and presented fewer comorbidities (p Conclusions IDUIE represents a considerable proportion of overall cases of IE, mainly affecting young people. Staphylococcus aureus is the most common microbiologic agent. IDUIE is not associated with higher mortality but drug abuse is an independent predictor of mortality. Considering that patient with uncomplicated IE treated medically have a better prognosis, we should reserve surgery to patients with a strict indication for it. On the other hand, since there are no predictors of futility of surgery, all patients with a complicated IE should undergo surgery without delay. The main determinant of prognosis in these patients is not IE but drug abuse itself. For this reason, increased focus on addiction treatment following hospital discharge is mandatory to improve long term prognosis. Funding Acknowledgement Type of funding sources: None.

Introduction Most cases of infective endocarditis (IE) involve a single valve, and little is known concerning IE that simultaneously affects two valves. The involvement of more than one valve may imply more severe and extensive cardiac lesions. In these patients, surgery may be challenging. Purpose We aimed to determine the clinical characteristics, the therapeutic strategy, and the prognostic impact of double-valve IE (DVIE). Method We retrospectively included in the analysis 380 consecutive patients with definite active IE in a single surgical centre. The univariate and multivariate long-term survival was analysed by the Kaplan-Meier method and by stepwise Cox proportional hazards models, respectively. We repeated the mortality analysis using the propensity score matching technique, to adjust for baseline differences between SVIE and DVIE groups. Results DVIE occurred in 60 of the total enrolled 380 patients (15.8%) and involved mostly the combination of mitral and aortic valves (N=52, 87%). Most patients had double-native IE (N=38, 63%). Staphylococci were significantly less frequent in patients with double-valve than single-valve IE (SVIE). The proportion of patients undergoing valve repair among those treated surgically was higher for patients with DVIE than for SVIE (p Conclusions DVIE represents a considerable proportion of overall cases of IE, mainly involving aortic and mitral valves, with a jet lesion on the mitral valve; Staphylococcus is significantly less frequent than in SVIE; DVIE is independently associated with higher mortality; finally, mitral valve repair is feasible in a considerable proportion of surgical cases. Funding Acknowledgement Type of funding sources: None. Propensity score matchingKaplan-Meier analysis: survival of DVIE

Background Valve repair is considered the treatment of choice for native mitral and tricuspid valve regurgitation but the rate of feasibility when the defect is caused by acute infective endocarditis (IE) is debated. We report the experience of valve repair versus replacement following IE in a high-volume surgical center. Methods We retrospectively analyzed 351 consecutive patients (123 women) admitted to our department with definite diagnosis of IE. IE occurred on native valves in 219 patients (62%) and on prosthetic valves in 132 (38%). Among native valves, IE involved the aortic valve in 105 cases (48%), mitral valve in 97 cases (44%) and tricuspid valve in 17 (8%). Since only native mitral and tricuspid valves are elegible for surgical repair, we limited the analysis to this subset (114 patients); of them, 92 (80.7%) underwent surgery (the final cohort) and 22 were treated conservatively, 13 due to absence of surgical indication and 9 due to prohibitive surgical risk. Long-term follow-up was obtained by structured telephone interviews. Primary endpoints were mortality and freedom from recurrent endocarditis. Secondary endpoints were the postoperative incidence of major adverse events (hospitalization for any cause, pace-maker implantation, new onset of atrial fibrillation, sternal dehiscence). Results Mean age at surgery was 61.9 years (SD 14.5). Mean vegetation length was 11.6 mm (SD 8.8). Endocarditis was left-sided in 80 (87%). Among the 92 surgical patients, 58 (63%) underwent valve replacement and 34 valve repair (37%). Mortality was similar between valve repair and replacement (15 vs 12%). Adverse events rate (19% vs 16%) and relapse were not statistically different between repair and replacement procedures. Conclusions The present study shows that a sizeable subgroup of consecutive patients with native mitral or tricuspid IE are amenable to valve repair in expert hands. Outcome of repair in IE is comparable to valve replacement mid-term, and should be considered whenever possible, as in degenerative valve disease. Funding Acknowledgement Type of funding source: None

Background Despite optimal medical and surgical treatment, mortality in infective endocarditis (IE) remains high. Aim of this study was to identify predictors of long term mortality for any cause, adverse event rate, relapse rate and valvular dysfunction at follow-up, in a high-volume surgical center. Methods We retrospectively analyzed 358 consecutive patients (127 women) admitted to our department with definite diagnosis of IE not device-related. IE occurred on native valves in 224 patients (63%); the infection involved the aortic valve in 192 (54%), mitral valve in 139 (39%) and tricuspid valve in 26 (7%). Overall 285 (80%) patients underwent surgery and 73 (20%) were treated conservatively, 38 due to absence of surgical indication and 35 due to refusal or prohibitive surgical risk. Long-term follow-up was obtained by structured telephone interviews. Primary endpoints were all-cause mortality, freedom from recurrent endocarditis, postoperative incidence of major adverse events (hospitalization for any cause, pace-maker implantation, new onset of atrial fibrillation, sternal dehiscence), worsening of left ventricular ejection fraction (LVEF) and valvular dysfunction. Results Mean age was 65 years (SD 15.2). Mean vegetation length was 8.9 mm (SD 7.6). Endocarditis was left-sided in 332 (93%). Average follow-up was 6 months. At univariable analysis, mortality was associated with female gender (p=0.031), age (p Conclusions The present study shows that low EF, EuroSCORE2, procalcitonin levels and diabetes are independent predictors of death in patients with IE. Non-fatal adverse events are more frequent in patients with renal failure. Relapse rate is higher in drug abusers. These informations may help personalize follow-up strategies after acute admission for IE. Funding Acknowledgement Type of funding source: None

Objectives. Valve repair is considered the treatment of choice for native mitral valve regurgitation, although the rate of feasibility when the defect is caused by acute infective endocarditis (IE) is debated. We report the experience of valve repair versus replacement following IE in a high-volume surgical center. Methods. We retrospectively analyzed 363 consecutive patients (123 women) admitted with a diagnosis of definite IE. We selected 108 patients with native mitral IE, potentially eligible for surgical repair. Of these 108, 90 (83%) underwent surgery and 18 were treated conservatively. The two primary endpoints were all-cause mortality and freedom from recurrent endocarditis. Results. Mean age at surgery was 63.6 years (SD 13.5). Mean vegetation length was 11.6 mm (SD 7.7). Among the 90 surgical patients, 57 (63%) underwent valve replacement and 33 valve repair (37%). Mean follow-up duration was three years. All-cause short-term (30 days: 3±3 vs 4±2% for repair and replacement respectively) and long-term (3 years: 26±9 vs. 36±11%) mortality was lower, although not-significantly, for valve repair (figure 1), as well as nonfatal adverse events (15±4 vs. 20±2%) and relapse rate (1±1% vs. 3±1%) at three years. At echocardiographic follow-up, no differences were reported between the two groups in terms of left ventricular systolic function and valvular continence. Conclusions. In our experience, over one-third of consecutive patients with native mitral are amenable to valve repair in expert hands. Mid-term outcome of repair in IE is comparable to valve replacement, and should be considered whenever possible, as in degenerative valve disease.