Background: Contemporary guidelines recommend rapid initiation of four classes of guideline-directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction (HFrEF); however, real-world persistence, adherence, and dose optimization remain suboptimal. Methods: We analysed a predefined subregistry within the prospective Cardiology Research Dubrava (CaRD) registry, a real-world HF registry at a tertiary centre that includes patients across the ejection-fraction spectrum in whom contemporary HF therapy, including sodium-glucose cotransporter 2 inhibitors (SGLT2i), is introduced or optimised in routine practice. For this analysis, we included patients with newly diagnosed HFrEF (left ventricular ejection fraction (LVEF) ≤ 40%) who were discharged on all four GDMT classes; 167 of 179 patients with newly diagnosed HFrEF during the study period had an available 6-month medication assessment and comprised the final analytic cohort. The four GDMT pillars (beta-blocker; angiotensin-converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB), or angiotensin receptor-neprilysin inhibitor (ARNI); mineralocorticoid receptor antagonist (MRA); and SGLT2i) were initiated within 4 days when clinically feasible. Medication adherence and target-dose attainment were assessed at 6, 12, and 24 months using a structured self-report questionnaire. Major adverse events (MAE) and all-cause mortality were recorded over 24 months. Patients were classified as adherent if they reported regular intake (≥80% of prescribed doses) of all four drug classes at 6 months; otherwise, they were classified as nonadherent. Results: Among the 167 analysed patients (median age 64 years, 74% men, median LVEF 30%), regular adherence at 6, 12, and 24 months was 65%, 55%, and 59% for beta-blockers; 66%, 50%, and 49% for ACEi/ARB/ARNI; 62%, 52%, and 49% for MRAs; and 84%, 57%, and 68% for SGLT2i. Target doses were achieved in 25-33% for beta-blockers, 42-50% for ACEi/ARB/ARNI, and 73-78% for MRAs. At 24 months, 56 survivors (37%) were adherent to all four drug classes. Over 24 months, all-cause mortality was 9.0% and MAE 18.6%, occurring less frequently in adherent vs. nonadherent patients (mortality 0% vs. 13.5%; MAE 8.9% vs. 23.4%). Conclusions: In this real-world, non-randomized HFrEF subregistry, in-hospital initiation of quadruple GDMT was feasible, yet maintaining long-term adherence and achieving target doses remained challenging. These data underscore the gap between guideline recommendations and routine practice and support structured follow-up and protocol-driven titration to optimize implementation.

Background: Intravascular hemolysis is a common complication in patients undergoing extracorporeal membrane oxygenation (ECMO), with plasma free hemoglobin (pfHb) serving as a biomarker for detection. Without standardized protocols, laboratories face challenges in interpreting and reporting results. Hemolysis indices may enhance reporting accuracy. Methods: This retrospective observational study at University Hospital Center Zagreb included 61 lithium heparin plasma samples from ECMO patients. pfHb was measured using the Harboe method (fHb) and estimated from hemolysis indices on Abbott Alinity c analyzer (efHb). Total and conjugated bilirubin, hemolysis, icterus, and lipemia indices (HIL) were recorded. Method comparison used Passing-Bablok regression and Bland-Altman analysis. An algorithm for pfHb reporting accounting for HIL interferences was developed. Results: Significant differences were observed between methods, with Harboe yielding higher median fHb (261 mg/L) versus efHb (58 mg/L). Regression analysis showed constant negative bias of -91 mg/L (95% CI: -143 to -16) for efHb relative to fHb. Bland-Altman analysis demonstrated wide limits of agreement. Correlation between fHb and efHb was moderate (Spearman's rho = 0.618, p < 0.001). The delta between methods increased with higher bilirubin concentrations. An algorithm integrating HIL indices with the Harboe method was developed to guide result validation and reporting. Conclusions: Accurate hemolysis assessment in ECMO patients requires careful interpretation, appropriate method selection, and laboratory-clinician collaboration. The proposed algorithm improves the clinical utility of pfHb testing by accounting for analytical interferences and supporting informed decision-making.

Noninvasive ventilation (NIV) has become a key method in emergency medicine for the management of acute respiratory failure (ARF) and is often one of the most critical scenarios in emergency settings. This paper reviews the latest noninvasive ventilation strategies, including high-flow nasal cannula (HFNC) and noninvasive positive airway pressure (CPAP, BiPAP), and their effectiveness in emergency medical settings. It also discusses the use of NIV in various emergencies including cardiogenic pulmonary edema, acute exacerbation of chronic obstructive pulmonary disease (COPD), and hypoxemic respiratory failure. Finally, this paper reviews the challenges in implementing noninvasive ventilation in emergencies and its advantages compared to invasive approaches.

Objective:Ceftazidime/avibactam (CZA) is an essential treatment option for managing infections caused by multidrug-resistant (MDR) Gram-negative (G-) bacteria, including Klebsiella pneumoniae OXA-48 and carbapenem-resistant Pseudomonas aeruginosa. Growing evidence indicates that critically ill intensive care unit (ICU) patients often exhibit altered pharmacokinetics (PK) of CZA, which may compromise the achievement of optimal PK/pharmacodynamic (PD) targets with standard dosing regimens. The primary hypothesis of this study is that continuous infusion (CI) of CZA improves microbiological success compared to intermittent dosing (ID) in critically ill ICU patients with severe infections caused by K. pneumoniae OXA-48 or P. aeruginosa. Methods:This is a single-center, randomized, open-label trial with a 1:1 allocation ratio, conducted at the University Hospital Centre Zagreb, a tertiary care hospital in Croatia. A total of 140 critically ill ICU patients with severe infections due to K. pneumoniae OXA-48 or P. aeruginosa requiring CZA treatment will be randomized to receive either ID of CZA (2 g/0.5 g/8 h over 2 h) or the same total daily dose in CI (6 g/1.5 g over 24 h). The study is powered to demonstrate the superiority of CI over ID of CZA in terms of microbiological success. Outcomes:The primary outcome will be microbiological success rate, chosen as a key indicator of pathogen eradication that is directly influenced by PK/PD target attainment. Secondary outcomes will include clinical success rate, time to symptoms improvement, length of ICU stay, length of hospital stay, all-cause 28-day mortality, pathogen recurrence rate on day 28, time to weaning from mechanical ventilation, cumulative vasoactive-inotropic score, adverse events, and the ratio of ceftazidime plasma concentration to the pathogen's minimum inhibitory concentration (C/MIC). Conclusion:This trial will provide evidence on optimal CZA administration regimen in critically ill ICU patients with severe infections due to MDR G-pathogens. Clinica Trial Registration:clinicaltrials.gov, identifier NCT06811727.

Introduction Nosocomial infections in patients undergoing extracorporeal membrane oxygenation (ECMO) are common and associated with poorer outcomes. This study aimed to analyze the efficacy of the Seraph filter in reducing circuit-related infections and improving clinical outcomes in COVID-19 patients treated with ECMO. Methods In 13 patients who required ECMO support, circuit-related infections were diagnosed based on either local signs of infection accompanied by positive microbiological samples taken locally or positive blood cultures. Hemoadsorption was performed using Seraph 100 in series with the dialyzer for 4-6 h. Blood cultures were also sampled both before and 24 h after treatment with Seraph 100. Results Sterile blood cultures were achieved in 53.8% of all patients. Blood cultures were found to be sterile from fungi (Candida parapsilosis/glabrata) and Stenotrophomonas malthophilia in all patients. In addition, the blood cultures were sterile from Klebsiella pneumoniae in 60%, Staphylococcus epidermidis in 75%, and Acinetobacter baumanii in 50% of all patients. We observed a significant reduction in vasopressor doses, an improvement in respiratory parameters, and a significant decrease in the sequential organ failure assessment (SOFA) score on the first day after treatment with Seraph 100. Conclusion This is the first study on ECMO patients treated with Seraph 100 for circuit-related infections. It shows a significant percentage of negative blood cultures after hemadsorption, particularly for fungal infections. These findings should be validated in multicenter prospective studies.

Background:The coronavirus disease 2019 (COVID-19) patients with hypogammaglobulinemia who are sick enough to require intensive care unit (ICU) admission exhibit high mortality rates. This study investigates whether the use of rescue hemoadsorption is associated with increased survival and/or improved clinical and biological parameters.Methods:In this prospective study, critically ill COVID-19 patients were consecutively enrolled, and serum protein electrophoresis was used to screen for hypogammaglobulinemia (defined as a gamma-globulin fraction below the 10th percentile and confirmed by a serum IgG level below 700 mg/dL). Twelve patients received hemoadsorption for immunomodulation. The same laboratory parameters were collected from 24 propensity-matched control patients who did not receive hemoadsorption.Results:There was no significant survival difference between patients treated with hemoadsorption and control patients. There was also no significant post-treatment improvement in the clinical parameters or sequential organ failure assessment (SOFA) scores for patients who received hemoadsorption compared to those who did not. Notably, 90% of all patients (32/36) died before day 28, regardless of whether they received hemoadsorption. An independent association between hypogammaglobulinemia and death within 28 days was found for all patients: Hazard ratio (HR) 0.32 (0.15, 0.66), P < 0.001.Conclusion:Hemoadsorption was not associated with increased survival in COVID-19 ICU patients with hypogammaglobulinemia. Our study highlights that a diagnosis of impaired humoral immunity could be a useful clinical predictor of high mortality and of non-response to hemoadsorption for patients with severe COVID-19.

OBJECTIVE:To present a case of encephalopathy after the administration of an iodinated contrast medium in a coronary angiography procedure. CASE SUMMARY:A 75-year-old male heart transplant recipient with cardiac allograft vasculopathy underwent coronary angiography followed by percutaneous coronary intervention. An iodinated contrast medium, ioversol, was used. Two hours later, the patient had focal impaired awareness seizure (unresponsive, head and gaze deviated to the left, with oroalimentary and gestural automatisms). Brain imaging showed no acute lesions or perfusion deficits. Electroencephalography revealed the focal slowing on the right fronto-temporal and left fronto-centro-temporal region, as well as paroxysmal discharges of high voltage delta activity (encephalopathic pattern). The patient was treated with intravenous levetiracetam. The symptoms completely resolved the next day, and the patient was discharged after 5 days of hospitalization. DISCUSSION:Contrast-induced encephalopathy (CIE) is an extremely rare complication of cardiac catheterization, with an incidence of 0.06%. Although the exact pathophysiology of this disorder is still not completely understood, it has been hypothesized that hyperosmolar contrast agent causes the shrinkage of endothelial cells, followed by the opening of tight junctions and the disruption of the blood-brain barrier resulting in direct neurotoxicity of the iodinated contrast medium. CONCLUSION:CIE is a rare complication of cardiac catheterization, likely under-recognized and under-diagnosed due to its variable clinical features, unremarkable or nonspecific radiological findings, and a lack of well-defined diagnostic criteria. Despite the challenging diagnosis and a lack of evidence for treatment strategies, the prognosis is good with supportive therapy.

Background: Patients undergoing prolonged mechanical ventilation commonly require tracheotomy. The main aim of this study was to evaluate the outcomes of tracheotomy for patients with acute respiratory distress syndrome (ARDS) associated with COVID-19 in low-resource settings. Methods: A retrospective, single-center, observational cohort study was performed on patients with ARDS associated with COVID-19. Patients who underwent intubation alone were compared with those who received both intubation and subsequent tracheotomy. The analysis included patient demographics, comorbidities, and outcomes. Results: Patients undergoing tracheotomy (n = 89) were compared with intubated patients (n = 622). The median time from intubation to tracheotomy was 10 days (IQR: 6–15 days). Overall, 608 patients (85.5%) died in the hospital. Thirty-seven patients (35.9%) in the survival group had tracheostomy compared with fifty-two patients (8.5%) in the non-survival group (p < 0.001). The Kaplan–Meier curve shows a higher probability of survival in the tracheotomy group compared with the non-tracheotomy group (log-rank test: p < 0.001). Tracheotomy was found to be independently associated with lower in-hospital mortality (HR = 0.16 [95% CI: 0.11–0.23], p < 0.001) in the multivariable Cox proportional hazards regression analysis after adjusting for potential confounding factors. Furthermore, tracheotomy was associated with a higher cumulative incidence of being alive and off the ventilator at day 28 (SHR = 2.87 [95% CI: 1.88–4.38], p < 0.001). Conclusions: Tracheotomy was associated with reduced in-hospital mortality and longer ventilator-free days.

Introduction. Ceftazidime/avibactam, a novel beta-lactam antibiotic, demonstrates time-dependent bacterial killing; thus, new reports advocate its administration as a continuous infusion, as opposed to bolus or prolonged infusion application. Methods. Critically ill COVID-19 patients (n=10) superinfected with OXA-48-producing Klebsiella pneumoniae susceptible to ceftazidime/avibactam were treated with ceftazidime/avibactam as a continuous infusion for an average of 10 days. The treatment regimen included an initial loading dose, followed by a continuous infusion of ceftazidime/avibactam. These patients were immunocompromised because of severe COVID-19, treatment with corticosteroids, and some solid organ transplant recipients (n=2), all with high disease severity scores. Discussion. Considering the published literature to this date, this is the one of first reports describing the real-life results of using a continuous infusion of ceftazidime/avibactam in the treatment of OXA-48-producing K. pneumoniae superinfection in critically ill COVID-19 patients. Microbiological effectiveness of treatment, evidenced by negativization of microbiological samples, was achieved in eight cases (80%) overall, but in patients with sepsis and urinary tract infection, the cure rate was 100%. Conclusion. The reasons for the low treatment success rates in pneumonia caused by OXA-48-producing K. pneumoniae could be explained by the concurrent severe COVID-19 pneumonia.

U razdoblju pandemije koronavirusne bolesti 2019. (COVID-19) mnogi bolesnici kojima je bila potrebna invazivna mehanička ventilacija, primljeni su u jedinice intenzivnog liječenja (JIL) zbog teškog respiratornog zatajenja povezanog s bolešću COVID-19. Prijam u JIL i invazivna mehanička ventilacija neovisni su rizici za pneumoniju povezanu s ventilatorom (engl . ventilator associated pneumonia; VAP ) , kod koje je zabilježena visoka stopa smrtnosti i dulji boravak u JIL-u te je produljeno bolničko liječenje. Ako govorimo o uzročnicima VAP-a, Pseudomonas aeruginosa bio je jedan od glavnih gram-negativnih nefermentirajućih uzročnika ove patologije, zajedno s Burkholderia cepacia i Stenotrophomonas maltophilia u manjoj mjeri. Protiv gram-negativnih mikroorganizama otpornih na karbapeneme, ceftazidim/avibaktam (CZA) jedan je od najčešće korištenih antimikrobnih lijekova. Cilj ovog preglednog članka bio je opisati korištenje CZA u liječenju bolesnika s infekcijom COVID-19 koji su razvili VAP uzrokovan P. aeruginosa , B. cepacia i S. maltophilia , usporediti to s podatcima objavljenim u literaturi te skrenuti pozornost na kontinuiranu primjenu lijeka kao drugačijeg modaliteta u odnosu na standardni način primjene u bolusu. Unatoč visokoj smrtnosti kritično oboljelih bolesnika s COVID-om, CZA predstavlja valjanu opciju liječenja VAP-a uzrokovanog nefermentirajućim gram-negativnim mikroorganizmima.

As patients with congenital heart disease (CHD) continue to enjoy longer lives, non-congenital cardiologists and other healthcare professionals are increasingly encountering them in their practice and are challenged by their specific needs. Most under- and post-graduate medical training tends to overlook this common pathology, resulting in insufficient awareness of post-repair or post-palliation residual lesions and sequelae from previous interventions. In a strive towards improving the quality of care for this ever-growing cardiovascular patient cohort, it is prudent to outline the areas of concern and specific management needs pertaining to adult patients with CHD and share it with non-CHD professionals. The purpose of this paper is to offer essential guidance to physicians, including cardiologists, when they encounter a patient with CHD in a non-congenital healthcare setting.