Unveiling the Role of Endothelial Dysfunction: A Possible Key to Enhancing Catheter Ablation Success in Atrial Fibrillation.

Atrial fibrillation, a prevalent type of arrhythmia, is increasingly contributing to the economic burden on healthcare systems. The development of innovative treatments, notably catheter ablation, has demonstrated both impressive and promising outcomes. However, these treatments have not yet fully replaced pharmaceutical approaches, primarily due to the relatively high incidence of atrial fibrillation recurrence post-procedure. Recent insights into endothelial dysfunction have shed light on its role in both the onset and progression of atrial fibrillation. This emerging understanding suggests that endothelial function might significantly influence the effectiveness of catheter ablation. Consequently, a deeper exploration into endothelial dynamics could potentially elevate the status of catheter ablation, positioning it as a primary treatment option for atrial fibrillation.

From flatline to lifeline: A scoping review of the Lazarus phenomenon.

BACKGROUND: The Lazarus phenomenon or autoresuscitation (autoROSC) is the return of spontaneous circulation (ROSC) after the termination of the cardiopulmonary resuscitation (CPR) efforts. PURPOSE: The purpose of the current scoping review is to present the available data in the literature regarding autoROSC. METHODS: We reviewed four scientific databases to identify all studies which reported autoROSC cases in patients who underwent CPR. We then extracted all information relevant to CPR and autoROSC. The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. RESULTS: We identified 66 studies describing 76 autoROSC cases. The majority of cardiac arrests were in-hospital (44, 57.89%). Median time from termination of CPR to autoROSC was 5 min. Regarding the outcome, 52 (77.61%) patients died and 11 (14.47%) patients had intact neurological outcome. A higher mortality rate was identified in patients with respiratory comorbidities. Overall, 24 (31.58%) patients survived. CONCLUSION: AutoROSC is probably an under-reported event in the medical community. Healthcare professionals should be aware of the phenomenon and actively monitor for it, when appropriate.

Hemin accumulation and identification of a heme-binding protein clan in K562 cells by proteomic and computational analysis.

Heme (iron protoporphyrin IX) is an essential regulator conserved in all known organisms. We investigated the kinetics of intracellular accumulation of hemin (oxidized form) in human transformed proerythroid K562 cells using [14 C]-hemin and observed that it is time and temperature-dependent, affected by the presence of serum proteins, as well as the amphipathic/hydrophobic properties of hemin. Hemin-uptake exhibited saturation kinetics as a function of the concentration added, suggesting the involvement of a carrier-cell surface receptor-mediated process. The majority of intracellular hemin accumulated in the cytoplasm, while a substantial portion entered the nucleus. Cytosolic proteins isolated by hemin-agarose affinity column chromatography (HACC) were found to form stable complexes with [59 Fe]-hemin. The HACC fractionation and Liquid chromatography-mass spectrometry analysis of cytosolic, mitochondrial, and nuclear protein isolates from K562 cell extracts revealed the presence of a large number of hemin-binding proteins (HeBPs) of diverse ontologies, including heat shock proteins, cytoskeletal proteins, enzymes, and signaling proteins such as actinin a4, mitogen-activated protein kinase 1 as well as several others. The subsequent computational analysis of the identified HeBPs using HemoQuest confirmed the presence of various hemin/heme-binding motifs [C(X)nC, H, Y] in their primary structures and conformations. The possibility that these HeBPs contribute to a heme intracellular trafficking protein network involved in the homeostatic regulation of the pool and overall functions of heme is discussed.

Rapidly improving acute respiratory distress syndrome in COVID-19: a multi-centre observational study.

BACKGROUND: Before the pandemic of coronavirus disease (COVID-19), rapidly improving acute respiratory distress syndrome (ARDS), mostly defined by early extubation, had been recognized as an increasingly prevalent subphenotype (making up 15-24% of all ARDS cases), associated with good prognosis (10% mortality in ARDSNet trials). We attempted to determine the prevalence and prognosis of rapidly improving ARDS and of persistent severe ARDS related to COVID-19. METHODS: We included consecutive patients with COVID-19 receiving invasive mechanical ventilation in three intensive care units (ICU) during the second pandemic wave in Greece. We defined rapidly improving ARDS as extubation or a partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2:FiO2) greater than 300 on the first day following intubation. We defined persistent severe ARDS as PaO2:FiO2 of equal to or less than 100 on the second day following intubation. RESULTS: A total of 280 intubated patients met criteria of ARDS with a median PaO2:FiO2 of 125.0 (interquartile range 93.0-161.0) on day of intubation, and overall ICU-mortality of 52.5% (ranging from 24.3 to 66.9% across the three participating sites). Prevalence of rapidly improving ARDS was 3.9% (11 of 280 patients); no extubation occurred on the first day following intubation. ICU-mortality of patients with rapidly improving ARDS was 54.5%. This low prevalence and high mortality rate of rapidly improving ARDS were consistent across participating sites. Prevalence of persistent severe ARDS was 12.1% and corresponding mortality was 82.4%. CONCLUSIONS: Rapidly improving ARDS was not prevalent and was not associated with good prognosis among patients with COVID-19. This is starkly different from what has been previously reported for patients with ARDS not related to COVID-19. Our results on both rapidly improving ARDS and persistent severe ARDS may contribute to our understanding of trajectory of ARDS and its association with prognosis in patients with COVID-19.

Simulation to minimise patient self-inflicted lung injury: are we almost there?

Computational modelling has been used to enlighten pathophysiological issues in patients with acute respiratory distress syndrome (ARDS) using a sophisticated, integrated cardiopulmonary model. COVID-19 ARDS is a pathophysiologically distinct entity characterised by dissociation between impairment in gas exchange and respiratory system mechanics, especially in the early stages of ARDS. Weaver and colleagues used computational modelling to elucidate factors contributing to generation of patient self-inflicted lung injury, and evaluated the effects of various spontaneous respiratory efforts with different oxygenation and ventilatory support modes. Their findings indicate that mechanical forces generated in the lung parenchyma are only counterbalanced when the respiratory support mode reduces the intensity of respiratory efforts.

COVID-19 related peripheral arterial thrombotic events in intensive care unit and non-intensive care unit patients: A retrospective case series.

OBJECTIVES: COVID-19 associated arterial thrombosis has been attributed to multiple inflammation and coagulation mechanisms. The aim of this study was to report the experience of a tertiary center on COVID-19 patients managed for acute peripheral arterial thrombosis. METHODS: A single-center case series was conducted, including retrospectively collected data from all COVID-19 patients presenting arterial thrombosis, from March 2020 to February 2022. Intensive care unit (ICU) and non-ICU cases were included. The primary outcomes were mortality, successful revascularization, and amputation at 30 days. RESULTS: Twenty patients presented peripheral arterial thrombosis (90% males, mean age 65 years (16-82 years)). Eighteen were diagnosed with the Delta variant and none was previously vaccinated. All cases presented acute lower limb ischemia; in 20% with bilateral involvement. Nine patients were hospitalized in the ward while 11 in the ICU. From the non-ICU cases, five presented Rutherford IIb and four cases, Rutherford's IIa ischemia. Six cases underwent revascularization (67%). Two of them were finally amputated (33%) and two died during hospitalization (33%). Two revascularizations were considered successful (33%). The ICU group presented mainly with Rutherford's III ischemia (54.5%). The mortality in the ICU cohort was 72.7%. Only one patient underwent successful revascularization and two were amputated in this subgroup. Early mortality was 50% for the total cohort while the type of management was not related to mortality. CONCLUSIONS: Covid-19 related arterial thrombosis in non-vaccinated population is associated with 50% early mortality; increased up to 72% in the ICU patients. The amputation rate was 20% while only 40% of the revascularizations were considered successful.

The role of antimicrobial resistance on long-term mortality and quality of life in critically ill patients: a prospective longitudinal 2-year study.

BACKGROUND: In the recent era, antimicrobial resistance has been identified as one of the most important threats to human health worldwide. The rapid emergence of antibiotic-resistant pathogens (ABRP) in the modern intensive care unit (ICU) also represents a "nightmare scenario" with unknown clinical consequences. In the Greek ICU, in particular, gram negative ABRPs are now considered endemic. However, the possible longitudinal impact of ABRPs on long-term outcomes of ICU patients has not yet been determined. METHODS: In this two-year (January 2014-December 2015) single-centre observational longitudinal study, 351 non-neurocritical ICU patients ≥ 18 year-old were enrolled. Patients' demographic, clinical and outcome data were prospectively collected. Quality-adjusted life years (QALY) were calculated at 6, 12, 18 and 24 months after ICU admission. RESULTS: Fifty-eight patients developed infections due to ABRP (ABRP group), 57 due to non-ABRP (non-ABRP group), and 236 demonstrated no infection (no-infection group) while in ICU. Multiple regression analysis revealed that multiple organ dysfunction syndrome score (OR: 0.676, 95%CI 0.584-0.782; P < 0.001) and continuous renal replacement therapy (OR: 4.453, 95%CI 1.805-10.982; P = 0.001) were the only independent determinants for ABRP infections in ICU. Intra-ICU, 90-day and 2-year mortality was 27.9%, 52.4% and 61.5%, respectively. Compared to the non-ABRP and no-infection group, the ABRP group demonstrated increased intra-ICU, 90-day and 2-year mortality (P ≤ 0.022), worse 2-year survival rates in ICU patients overall and ICU survivor subset (Log-rank test, P ≤ 0.046), and poorer progress over time in 2-year QALY kinetics in ICU population overall, ICU survivor and 2-year survivor subgroups (P ≤ 0.013). ABRP group was further divided into multi-drug and extensively-drug resistant subgroups [MDR (n = 34) / XDR (n = 24), respectively]. Compared to MDR subgroup, the XDR subgroup demonstrated increased ICU, 90-day and 2-year mortality (P ≤ 0.031), but similar 90-day and 2-year QALYs (P ≥ 0.549). ABRP infections overall (HR = 1.778, 95% CI 1.166-2.711; P = 0.008), as well as XDR [HR = 1.889, 95% CI 1.075-3.320; P = 0.027) but not MDR pathogens, were independently associated with 2-year mortality, after adjusting for several covariates of critical illness. CONCLUSIONS: The present study may suggest a significant association between ABRP (especially XDR) infections in ICU and increased mortality and inability rates for a prolonged period post-discharge that requires further attention in larger-scale studies.

Video Laryngoscopy Improves Intubation Times With Level C Personal Protective Equipment in Novice Physicians: A Randomized Cross-Over Manikin Study.

BACKGROUND: The use of video laryngoscopes by novice physicians may improve first-pass success rates compared with direct laryngoscopy. OBJECTIVE: The aim of the present study was to assess whether time to intubation, number of laryngoscopy attempts, and first-pass success rate during laryngoscopy with the video laryngoscope or conventional Macintosh laryngoscope are affected by personal protective equipment (PPE) donning. METHODS: Seventy inexperienced physicians were randomly assigned to video laryngoscope or Macintosh groups and were instructed to perform intubation with both devices on a manikin, using PPE or a standard uniform. The primary outcomes were insertion time, number of laryngoscopy attempts, and first-pass success rates for each device with or without donning PPE. RESULTS: In the Macintosh group, significantly less time was needed for the first successful intubation without PPE vs. with PPE (12.17 ± 3.69 s vs. 24.07 ± 5.09 s, respectively; p < 0.0001). On the other hand, such difference was not observed in the video laryngoscope group (14.99 ± 3.01 s vs. 14.01 ± 3.35 s, respectively; p = 0.07). With PPE, the first-pass success rate was significantly higher in the video laryngoscope group [41 (58.6%) vs. 66 (94.3%), p < 0.001]. The use of the video laryngoscope resulted in a significant decrease in insertion time compared with the Macintosh blade (14.01 ± 3.35 s vs. 24.07 ± 5.09 s, respectively; p < 0.0001). CONCLUSION: First-pass success and insertion time with the video laryngoscope were not affected by PPE donning. However, both were negatively affected with the Macintosh laryngoscope.

Ceftazidime-Avibactam To Treat Life-Threatening Infections by Carbapenem-Resistant Pathogens in Critically Ill Mechanically Ventilated Patients.

Data on the effectiveness of ceftazidime-avibactam (CAZ-AVI) in critically ill, mechanically ventilated patients are limited. The present retrospective observational cohort study, which was conducted in two general intensive care units (ICUs) in central Greece, compared critically ill, mechanically ventilated patients suffering from carbapenem-resistant Enterobacteriaceae (CRE) infections receiving CAZ-AVI to patients who received appropriate available antibiotic therapy. Clinical and microbiological outcomes and safety issues were evaluated. A secondary analysis in patients with bloodstream infections (BSIs) was conducted. Forty-one patients that received CAZ-AVI (the CAZ-AVI group) were compared to 36 patients that received antibiotics other than CAZ-AVI (the control group). There was a significant improvement in the Sequential Organ Failure Assessment (SOFA) score on days 4 and 10 in the CAZ-AVI group compared to that in the control group (P = 0.006, and P = 0.003, respectively). Microbiological eradication was accomplished in 33/35 (94.3%) patients in the CAZ-AVI group and 21/31 (67.7%) patients in the control group (P = 0.021), and clinical cure was observed in 33/41 (80.5%) versus 19/36 (52.8%) patients (P = 0.010), respectively. The results were similar in the BSI subgroups for both outcomes (P = 0.038 and P = 0.014, respectively). The 28-day survival was 85.4% in the CAZ-AVI group and 61.1% in the control group (log-rank test = 0.035), while there were 2 and 12 relapses in the CAZ-AVI and control groups, respectively (P = 0.042). A CAZ-AVI-containing regime was an independent predictor of survival and clinical cure (odds ratio [OR] = 5.575 and P = 0.012 and OR = 5.125 and P = 0.004, respectively), as was illness severity. No significant side effects were recorded. In conclusion, a CAZ-AVI-containing regime was more effective than other available antibiotic agents for the treatment of CRE infections in the high-risk, mechanically ventilated ICU population evaluated.

Malignant mesothelioma cells secrete natriuretic peptides: Data and diagnostic clinical implications.

BACKGROUND AND OBJECTIVE: Mesothelial cells and cardiomyocytes have shared embryonic mesodermal origin. Cardiomyocytes release BNP under stretch. We searched whether malignant mesothelioma cells also secrete BNP and if so, this has a meaningful impact. METHODS: Part I: Prospectively, patients with pleural lesions on CT having malignant mesothelioma effusions (MME, n = 13) were compared to patients with malignant effusions with pleural lesions (MEa, n = 14). Age-matched patients with ME without pleural lesions (MEb, n = 16) and non-malignant effusions (NME, n = 25) were analysed. Part II: Retrospectively, samples from patients with mesothelioma (n = 14), lung cancer (n = 8) or heart failure (n = 9) were used. BNP was measured in pleural fluid and blood/plasma. Part III: BNP was assessed in the culture supernatants of benign (MeT-5A) and malignant mesothelioma cell lines (M14K-epithelioid, MSTO-biphasic and ZL34-sarcomatoid) (n = 10 per cell line in three different biological replicates). RESULTS: In vitro, BNP concentration was significantly higher in the supernatant of all malignant cell lines than benign ones (P < 0.01), denoting BNP's production from the former. The pleural fluid to blood BNP ratio in MME was extremely high in Part I and Part II subjects (28.3 ± 12.1 and 25.9 ± 8.6, respectively) versus 1.1 ± 0.3 and 0.4 ± 0.1 in Part I ME and NME, respectively (P < 0.0001), and 0.8 ± 0.1 and 0.4 ± 0.1 in Part II ME and NME, respectively (P < 0.0001). BNP ratio ≥2.11 in Part I had 92% sensitivity and 94.5% specificity for MME (P < 0.0001). CONCLUSION: BNP is secreted from malignant mesothelial cells. In clinical practice, the pleural fluid to blood BNP ratio can help in the diagnosis of malignant mesothelioma.

Post-partum hemorrhage complicated by reverse-Takotsubo cardiogenic shock; a novel therapeutic approach.

Takotsubo Cardiomyopathy (TTC) is a type of transient, yet severe left ventricular systolic dysfunction, rarely complicating extreme emotional stress ("primary" TTC) or critical medical/surgical illness ("secondary" TTC forms). Although usually reversible, TTC may result in cardiogenic shock with dismal prognosis. "Secondary" TTC forms are particularly in danger for this complication, bearing significantly worse short and long-term prognosis. Herein, we report a rare case of a life-threatening "secondary" TTC in a patient with post-cesarean section severe hemorrhage, and we point out that early co-administration of esmolol and levosimendan might be an effective and safe therapeutic approach in "reversing" TTC-induced cardiogenic shock, especially when invasive therapeutic strategies are practically unfeasible.