Few data are available regarding the adherence to treatment guidelines in individuals with type 2 diabetes mellitus (T2DM) admitted to Internal Medicine Wards (IMW) while no information is available concerning the possible efficacy of an educational intervention aimed at improving adherence in this setting. To explore guidelines adherence and the associated impact on glycemic control in subjects with T2DM hospitalized in IMW before and after an educational intervention, we conducted a 3-phase, cluster-randomized, multicenter study. During Phase 1, we retrospectively collected data from patients with T2DM hospitalized for any cause in IMW for ≥5 days. In Phase 2, an educational training, based on the method of the educational outreach visits (EOV), was developed in 36 out of the 54 centers involved. In Phase 3, conducted 6 months after the training, we replicated the collection of data performed in Phase 1. Overall, we analyzed data from 1909 and 1662 individuals with T2DM during Phase 1 and Phase 3 of the study, respectively. No changes were observed in the difference between mean fasting glycemia levels at discharge vs at admission in Phase 3 comparing EOV vs NO EOV groups. A statistically significant increase in adherence to guidelines was observed from Phase 1 to Phase 3 and a trend toward higher adherence was detected when comparing the EOV and the no EOV groups. A structured educational intervention improves adherence to guidelines for managing T2DM in individuals admitted to IMW but has no effect on short-term glycemic control.
Stepwise layered provisional stenting (PS) is the most commonly used strategy to treat coronary bifurcation lesions (CBL). The term 'stepwise layered' emphasises the versatility of this approach that allows the adjustment of the procedure plan according to the CBL complexity, starting with stent implantation in one branch and implantation of a second stent in the other branch only when required. A series of refinements have been implemented over the years to facilitate the achievement of predictable procedural results using this approach. However, despite its simplicity and versatility, operators using this technique require full knowledge of the pitfalls of each procedural step. Part I of this 16th European Bifurcation Club consensus paper provides a detailed step-by-step overview of the pitfalls and technical troubleshooting during the implantation of the first stent using the PS strategy for the treatment of CBL.
The heart is commonly involved in maternally inherited mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome caused by the MT-TL1 m.3243A>G mutation of the mitochondrial DNA. Heart transplantation (HTx) is controversial and has rarely been performed with conflicting results.We analyzed factors preventing HTx in consecutive adult patients with MELASMT-TL1:m.3243A>G cardiomyopathy diagnosed and followed during the last 23 years in our HTx referral center.The series consists of 14 unrelated adult probands who were referred for evaluation of cardiomyopathy from 1998 to 2021. None had a suspected diagnosis of MELAS before referral. All patients underwent clinical and genetic visit and counseling, mitochondrial DNA sequencing, cardiovascular investigation (including right heart catheterization and endomyocardial biopsy in 10), multidisciplinary assessment, and biochemical tests. Family screening identified 2 affected relatives.The cardiac phenotype was characterized by hypertrophic, concentric, nonobstructive cardiomyopathy that often evolved into a dilated cardiomyopathy-like phenotype. Of the 14 probands, 7 were potential candidates for HTx, 2 for heart and kidney Tx, and 1 was on the active HTx list for 3 years. None of the 10 probands underwent HTx. One is currently being evaluated for HTx. All had diabetes, hearing loss, and myopathy, and 10 had chronic kidney disease and progressive encephalomyopathy. During follow-up, 10 died from heart failure associated with multiorgan failure within 5 years of the genetic diagnosis.High risk of stroke-like episodes, chronic kidney disease, and wasting myopathy in MELASMT-TL1:m.3243A>G patients prevents activation of plans for HTx. As a result, the management of their cardiomyopathy in this syndromic context remains an unmet clinical need.
Background: Elderly patients in complete remission (CR) after first-line therapy for acute myeloid leukemia (AML) relapse within months unless additional therapy is given. In elderly patients with AML in CR after intensive chemotherapy, the HOVON 97 study reported on the efficacy and safety of azacitidine (5-Aza) post-remission therapy and the randomized QUAZAR trial showed that CC-486 as maintenance therapy was associated with significantly longer overall and relapse-free survival than placebo. We report final results of the QoLESS AZA-AMLE Phase III, randomized, open label, Italian multicentre, trial to evaluate the efficacy of 5-Aza for post-remission therapy of elderly AML patients compared to best supportive care (BSC). Aims: The primary endpoint is disease-free survival (DFS, from CR to relapse/death at 2 and 5 years. Secondary endpoints are post-remission hospitalizations, overall survival (OS) at 2 and 5 years and changes in quality of life (QoL). Methods: Patients aged ≥ 61 years with untreated AML, “de novo” or evolving from MDS, fit for intensive chemotherapy but ineligible for stem cell transplantation received induction chemotherapy consisting of 2 courses of 3 + 7 (Daunorubicin 40 mg/m2 daily days 1-3 and cytarabine 100 mg/m2 intravenous infusion days 1-7. Cases in CR received cytarabine 800 mg/m2 3-hour infusion twice daily for 3 days. Patients in CR were randomized to receive BSC or 5-Aza 50 mg/m2 for 7 days every 28 days and dose increase after 1st cycle to 75 mg/m2 for further 5 cycles, followed by cycles every 56 days for 4.5 years. QoL was assessed with QOL-E version 3 and EORTC QLQ-C30 version 3.0. Results: 149 patients were enrolled to finally randomize 54 patients alive and in CR (Table 1). After randomization, no patients died before relapse, 7 cases completed the study while 43 subjects relapsed: at 2 years, 22 cases in BSC (median DFS: 6.0 months, 95% CI: 0.2–11.7) versus 18 in the 5-Aza arm (median DFS: 10.8 months, 95% CI: 1.9-19.6; p=0.20); at 5 years, 1 subject on BSC withdrew consent and 23 subjects relapsed (median DFS: 6.0 months, 95% CI: 0.2–11.7) while 2 subjects on 5-Aza withdrew consent, 1 discontinued for bladder cancer and 20 relapsed (median DFS: 10.8 months, 95% CI: 1.9-19.6; p=0.23). Age modified the effect of the allocation arm on DFS. Data adjustment for cytogenetic risk further amplified the efficacy of 5-Aza in patients aged >68 years, both at 2 (HR: 0.24, 95% CI: 0.08-0.69, P=0.008) and 5 years (HR: 0.28, 95% CI: 0.10-0.76, P=0.012). The effect of 5-Aza versus BSC tended to be statistically significant on DFS at 2 (P=0.053) and 5 years (P=0.068) in Cox models including cytogenetic risk and MRD as covariates. Kaplan-Meier analyses of the effect of 5-Aza on DFS (at 2 and 5 years) showed that patients aged >68 years and positive MRD tended to have a benefit in terms of DFS at both 2 and 5 years (P=0.056). In the 5-Aza arm, 5 subjects out of 27 (19%) were hospitalised whereas no patient was hospitalised in the BSC arm (P=0.023). QoL was similar in both arms after randomization. Twenty grade 3-4 adverse events, mainly neutropenia, occurred in 5-Aza versus 1 in BSC arm (p=0.002). Image:Summary/Conclusion: 5-Aza is well tolerated in elderly patients with AML who have achieved CR following standard chemotherapy. MRD remains an important predictor of DFS in the long-term, independent of 5-Aza maintenance. No statistically significant differences were observed between the two arms in terms of DFS, but after data adjustment it is suggested that patients aged >68 years and positive MRD may benefit from 5-Aza maintenance.
Background: No data are available regarding long-term survival of out-of-hospital cardiac arrest (OHCA) patients based on different Utstein subgroups, which are expected to significantly differ in terms of survival. We aimed to provide the first long-term survival analysis of OHCA patients divided according to Utstein categories. Methods: We analyzed all the 4,924 OHCA cases prospectively enrolled in the Lombardia Cardiac Arrest Registry (Lombardia CARe) from 2015 to 2019. Pre-hospital data, survival, and cerebral performance category score (CPC) at 1, 6, and 12 months and then every year up to 5 years after the event were analyzed for each patient. Results: A decrease in survival was observed during the follow-up in all the Utstein categories. The risk of death of the "all-EMS treated" group exceeded the general population for all the years of follow-up with standardized mortality ratios (SMRs) of 23 (95%CI, 16.8-30.2), 6.8 (95%CI, 3.8-10.7), 3.8 (95%CI, 1.7-6.7), 4.05 (95%CI, 1.9-6.9), and 2.6 (95%CI, 1.03-4.8) from the first to the fifth year of follow-up. The risk of death was higher also for the Utstein categories "shockable bystander witnessed" and "shockable bystander CPR": SMRs of 19.4 (95%CI, 11.3-29.8) and 19.4 (95%CI, 10.8-30.6) for the first year and of 6.8 (95%CI, 6.6-13) and 8.1 (95%CI, 3.1-15.3) for the second one, respectively. Similar results were observed considering the patients discharged with a CPC of 1-2. Conclusions: The mortality of OHCA patients discharged alive from the hospital is higher than the Italian standard population, also considering those with the most favorable OHCA characteristics and those discharged with good neurological outcome. Long-term follow-up should be included in the next Utstein-style revision.
