Axial functionalisation of photoactive diazido platinum(iv) anticancer complexes

Mono-axial functionalised octahedral diazido Pt(IV) complexes trans,trans,trans-[Pt(py)2(N3)2(OR1)(OR2)] (OR1 = OH and OR2 = anticancer agent coumarin-3 carboxylate (cou, 2a), pyruvate dehydrogenase kinase (PDK) inhibitors 4-phenylbutyrate (PhB, 2b) or dichloroacetate (DCA, 2c)), and their di-axial functionalised analogues with OR1 = DCA and OR2 = cou (3a), PhB (3b), or DCA (3c) have been synthesised and characterised, including the X-ray crystal structures of complexes 2a, 3a, 3b and 3c. These complexes exhibit dark stability and have the potential to generate cytotoxic Pt(II) species and free radicals selectively in cancer cells when irradiated. Mono-functionalised complexes 2a–2c showed higher aqueous solubility and more negative reduction potentials. Mono- and di-functionalised complexes displayed higher photocytotoxicity with blue light (1 h, 465 nm, 4.8 mW cm−2) than the parent dihydroxido complex 1 (OR1 = OR2 = OH) in A2780 human ovarian (IC50 0.9–2.9 μM for 2a–2c; 0.11–0.39 μM for 3a–3c) and A549 human lung cancer cells (5.4–7.8 μM for 2a–2c; 1.2–2.6 μM for 3a–3c) with satisfactory dark stability. Notably, no apparent dark cytotoxicity was observed in healthy lung MRC-5 fibroblasts for all complexes (IC50 > 20 μM). Significantly higher platinum cellular accumulation and photo-generated ROS levels were observed for the di-functionalised complexes compared with their mono-functionalised analogues when cancer cells were treated under the same concentrations

Remote monitoring and telemedicine in heart failure: implementation and benefits

Purpose of review: Remote monitoring (RM) of cardiac implantable electronic devices (CIEDs) is recommended as part of the individualized multidisciplinary follow-up of heart failure (HF) patients. Aim of this article is to critically review recent findings on RM, highlighting potential benefits and barriers to its implementation. Recent findings: Device-based RM is useful in the early detection of CIEDs technical issues and cardiac arrhythmias. Moreover, RM allows the continuous monitoring of several patients' clinical parameters associated with impending HF decompensation, but there is still uncertainty regarding its effectiveness in reducing mortality and hospitalizations. Summary: Implementation of RM strategies, together with a proactive physicians' attitude towards clinical actions in response to RM data reception, will make RM a more valuable tool, potentially leading to better outcomes

Biotinylated photoactive Pt(IV) anticancer complexes

Novel biotinylated diazido-Pt(IV) complexes exhibit high visible light photocytotoxicity while being stable in the dark. Photocytotoxicity and cellular accumulation of all-trans-[Pt(py)2(N3)2(biotin)(OH)] (2a) were enhanced significantly when bound to avidin; irradiation induced dramatic cellular morphological changes in human ovarian cancer cells treated with 2a

Low Occurrence of Infections and Death in a Real-World Cohort of Patients with Cardiac Implantable Electronic Devices

Background. The incidence of infections and death in patients implanted with cardiac implantable electronic devices (CIEDs) is not fully known yet. Aim. To describe the incidence of CIED-related infection and death, and their potential predictors in a contemporary cohort of CIED patients. Methods. All consecutive patients implanted with a CIED at our institution were prospectively enrolled. Follow-up visits were performed 2 weeks after CIED implantation for all patients, and then every 6 months for implantable cardioverter defibrillator (ICD)/cardiac resynchronization therapy (CRT) patients and every 12 months for pacemaker (PM) patients. The adjudication of CIED-related infections was performed by two independent investigators and potential disagreement was resolved by a senior investigator. Results. Between September 2016 and August 2020, a total of 838 patients were enrolled (34.6% female; median age 77 (69.6–83.6); median PADIT score 2 (2–4)). PMs were implanted in 569 (68%) patients and ICD/CRT in 269 (32%) patients. All patients had pre-implant antibiotic prophylaxis and 5.5% had an antibiotic-eluting envelope. Follow-up data were available for 832 (99.2%) patients. After a median follow-up of 42.3 (30.2–56.4) months, five (0.6%) patients had a CIED-related infection and 212 (25.5%) patients died. Using multivariate Cox regression analysis, end-stage chronic kidney disease (CKD) requiring dialysis and therapy with corticosteroids was independently associated with a higher risk of infection (hazard ratio (HR): 14.20; 95% confidence interval (CI) 1.48–136.62 and HR: 14.71; 95% CI 1.53–141.53, respectively). Age (HR: 1.07; 95% CI 1.05–1.09), end-stage CKD requiring dialysis (HR: 6.13; 95% CI 3.38–11.13) and history of atrial fibrillation (HR: 1.47; 95% CI 1.12–1.94) were independently associated with all-cause death. Conclusions. In a contemporary cohort of CIED patients, mortality was substantially high and associated with clinical factors depicting a population at risk. On the other hand, the incidence of CIED-related infections was low

Remote multiparametric monitoring and management of heart failure patients through cardiac implantable electronic devices

In this review we focus on heart failure (HF) which, as known, is associated with a substantial risk of hospitalizations and adverse cardiovascular outcomes, including death. In recent years, systems to monitor cardiac function and patient parameters have been developed with the aim to detect subclinical pathophysiological changes that precede worsening HF. Several patient-specific parameters can be remotely monitored through cardiac implantable electronic devices (CIED) and can be combined in multiparametric scores predicting patients’ risk of worsening HF with good sensitivity and moderate specificity. Early patient management at the time of pre-clinical alerts remotely transmitted by CIEDs to physicians might prevent hospitalizations. However, it is not clear yet which is the best diagnostic pathway for HF patients after a CIED alert, which kind of medications should be changed or escalated, and in which case in-hospital visits or in-hospital admissions are required. Finally, the specific role of healthcare professionals involved in HF patient management under remote monitoring is still matter of definition. We analyzed recent data on multiparametric monitoring of patients with HF through CIEDs. We provided practical insights on how to timely manage CIED alarms with the aim to prevent worsening HF. We also discussed the role of biomarkers and thoracic echo in this context, and potential organizational models including multidisciplinary teams for remote care of HF patients with CIEDs

Length of hospital stay for elective electrophysiological procedures: a survey from the European Heart Rhythm Association

AIMS: Electrophysiological (EP) operations that have traditionally involved long hospital lengths of stay (LOS) are now being undertaken as day case procedures. The coronavirus disease-19 pandemic served as an impetus for many centres to shorten LOS for EP procedures. This survey explores LOS for elective EP procedures in the modern era. METHODS AND RESULTS: An online survey consisting of 27 multiple-choice questions was completed by 245 respondents from 35 countries. With respect to de novo cardiac implantable electronic device (CIED) implantations, day case procedures were reported for 79.5% of implantable loop recorders, 13.3% of pacemakers (PMs), 10.4% of implantable cardioverter defibrillators (ICDs), and 10.2% of cardiac resynchronization therapy (CRT) devices. With respect to CIED generator replacements, day case procedures were reported for 61.7% of PMs, 49.2% of ICDs, and 48.2% of CRT devices. With regard to ablations, day case procedures were reported for 5.7% of atrial fibrillation (AF) ablations, 10.7% of left-sided ablations, and 17.5% of right-sided ablations. A LOS ≥ 2 days for CIED implantation was reported for 47.7% of PM, 54.5% of ICDs, and 56.9% of CRT devices and for 54.5% of AF ablations, 42.2% of right-sided ablations, and 46.1% of left-sided ablations. Reimbursement (43-56%) and bed availability (20-47%) were reported to have no consistent impact on the organization of elective procedures. CONCLUSION: There is a wide variation in the LOS for elective EP procedures. The LOS for some procedures appears disproportionate to their complexity. Neither reimbursement nor bed availability consistently influenced LOS

Cardiac Surgery in Jehovah's Witnesses Patients and Association With Peri-Operative Outcomes: A Systematic Review and Meta-Analysis

Background: Strategies for blood conservation, coupled with a careful preoperative assessment, may be applied to Jehovah's Witnesses (JW) patients who are candidates for cardiac surgery interventions. There is a need to assess clinical outcomes and safety of bloodless surgery in JW patients undergoing cardiac surgery. Methods: We performed a systematic review and meta-analysis of studies comparing JW patients with controls undergoing cardiac surgery. The primary endpoint was short-term mortality (in-hospital or 30-day mortality). Peri-procedural myocardial infarction, re-exploration for bleeding, pre-and postoperative Hb levels and cardiopulmonary bypass (CPB) time were also analyzed. Results: A total of 10 studies including 2,302 patients were included. The pooled analysis showed no substantial differences in terms of short-term mortality among the two groups (OR 1.13, 95% CI 0.74-1.73, I2=0%). There were no differences in peri-operative outcomes among JW patients and controls (OR 0.97, 95% CI 0.39-2.41, I2=18% for myocardial infarction; OR 0.80, 95% CI 0.51-1.25, I2=0% for re-exploration for bleeding). JW patients had a higher level of preoperative Hb (Standardized Mean Difference [SMD] 0.32, 95% CI 0.06-0.57) and a trend toward a higher level of postoperative Hb (SMD 0.44, 95% CI -0.01-0.90). A slightly lower CPB time emerged in JWs compared with controls (SMD -0.11, 95% CI -0.30-0.07). Conclusions: JW patients undergoing cardiac surgery, with avoidance of blood transfusions, did not have substantially different peri-operative outcomes compared with controls, with specific reference to mortality, myocardial infarction, and re-exploration for bleeding. Our results support the safety and feasibility of bloodless cardiac surgery, applying patient blood management strategies