Clinical characteristics and factors associated with ICU mortality during the first year of the SARS-Cov-2 pandemic in Romania: A prospective, cohort, multicentre study of 9000 patients.

BACKGROUND: The epidemiology of critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be different worldwide. Despite similarities in medicine quality and formation, there are also significant differences concerning healthcare and ICU organisation, staffing, financial resources and population compliance and adherence. Large cohort data of critically ill patients from Central and Eastern Europe are also lacking. OBJECTIVES: The study objectives were to describe the clinical characteristics of patients admitted to Romanian ICUs with SARS-CoV-2 infection and to identify the factors associated with ICU mortality. DESIGN: Prospective, cohort, observational study. SETTING: National recruitment, multicentre study, between March 2020 to March 2021. PATIENTS: All patients with SARS-CoV-2 infection admitted to Romanian ICUs were eligible. There were no exclusion criteria. INTERVENTION: None. MAIN OUTCOME MEASURE: ICU mortality. RESULTS: The statistical analysis included 9058 patients with definitive ICU outcome. The multivariable mixed effects logistic regression model found that age [odds ratio (OR) 1.27; 95% confidence interval (CI), 1.23 to 1.31], male gender (OR 1.21; 95% CI 1.05 to 1.4), medical history of neoplasia (OR 1.74; 95% CI, 1.36 to 2.22), chronic kidney disease (OR 1.54; 95% CI, 1.27 to 1.88), type II diabetes (OR 1.23; 95% CI, 1.06 to 1.43), chronic heart failure (OR 1.24; 95% CI, 1.03 to 1.49), dyspnoea (OR 1.3; 95% CI, 1.1 to 1.5), SpO2 less than 90% (OR 3; 95% CI, 2.5 to 3.5), admission SOFA score (OR 1.07; 95% CI, 1.05 to 1.09), acute respiratory distress syndrome (ARDS) on ICU admission (OR 1.35; 95% CI, 1.1 to 1.63) and the need for noninvasive (OR 1.8, 95% CI, 1.5 to 1.22) or invasive ventilation (OR 28; 95% CI, 22 to 35) and neuromuscular blockade (OR 3.5; 95% CI, 2.6 to 4.8), were associated with larger ICU mortality.Higher GCS on admission (OR 0.81; 95% CI, 0.79 to 0.83), treatment with hydroxychloroquine (OR 0.78; 95% CI, 0.64 to 0.95) and tocilizumab (OR 0.58; 95% CI, 0.48 to 0.71) were inversely associated with ICU mortality. CONCLUSION: The SARS-CoV-2 critically ill Romanian patients share common personal and clinical characteristics with published European cohorts. Public health measures and vaccination campaign should focus on patients at risk.

Perioperative trajectory of plasma viscosity: A prospective, observational, exploratory study in cardiac surgery.

OBJECTIVE: Plasma viscosity is one of the critical factors that regulate microcirculatory flow but has received scant research attention. The main objective of this study was to evaluate plasma viscosity in cardiac surgery with respect to perioperative trajectory, main determinants, and impact on outcome. METHODS: Prospective, single center, observational study, including 50 adult patients undergoing cardiac surgery with cardiopulmonary bypass between February 1, 2020 and May 31, 2021. Clinical perioperative characteristics, short term outcome, standard blood analysis, plasma viscosity, total proteins, and fibrinogen concentrations were recorded at 10 distinct time points during the first perioperative week. RESULTS: The longitudinal analysis showed that plasma viscosity is strongly influenced by proteins and measurement time points. Plasma viscosity showed a coefficient of variation of 11.3 ± 1.08 for EDTA and 12.1 ± 2.1 for citrate, similarly to total proteins and hemoglobin, but significantly lower than fibrinogen (p < .001). Plasma viscosity had lower percentage changes compared to hemoglobin (RANOVA, p < .001), fibrinogen (RANOVA, p < .001), and total proteins (RANOVA, p < .001). The main determinant of plasma viscosity was protein concentrations. No association with outcome was found, but the study may have been underpowered to detect it. CONCLUSION: Plasma viscosity had a low coefficient of variation and low perioperative changes, suggesting tight regulation. Studies linking plasma viscosity with outcome would require large patient cohorts.

COVID-19 Pandemic Was Associated with Lower Activity but Not Higher Perioperative Mortality in a Large Eastern European Center.

BACKGROUND Surges of critically ill patients can overwhelm hospitals during pandemic waves and disrupt essential surgical activity. This study aimed to determine whether hospital mortality increased during the COVID-19 pandemic and during pandemic waves. MATERIAL AND METHODS This was a retrospective analysis of a prospective, observational, epidemiological database. All patients who underwent surgery from January 1 to December 31, 2020, were included in the analysis. The setting was a large Eastern European Surgical Center referral center of liver transplant and liver surgery, a major center of abdominal surgery. RESULTS A total of 1078 patients were analyzed, and this number corresponded to a reduction of surgical activity by 30% during the year 2020 compared with 2019. Despite an increase in surgery complexity during the pandemic, perioperative mortality was not different, and this was maintained during the pandemic wave. The pandemic (OR 1.45 [0.65-3.22], P=0.365) and the wave period (OR 0.897 [0.4-2], P=0.79) were not associated with hospital mortality in univariate analysis. In the multivariate model analysis, only the American Society of Anesthesiology (ASA) score (OR 5.815 [2.9-11.67], P<0.0001), emergency surgery (OR 5.066 [2.24-11.48], P<0.0001), and need for surgical reintervention (OR 5.195 [1.78-15.16], P=0.003) were associated with hospital mortality. CONCLUSIONS Despite considerable challenges, in this large retrospective cohort, perioperative mortality was similar to that of pre-pandemic practice. Efforts should be made to optimize personnel issues, while maintaining COVID-19-free surgical pathways, to adequately address patients' surgical needs during the following waves of the pandemic.

Perioperative management of antiplatelet therapy in noncardiac surgery.

PURPOSE OF REVIEW: Perioperative management of antiplatelet agents (APAs) in the setting of noncardiac surgery is a controversial topic of balancing bleeding versus thrombotic risks. RECENT FINDINGS: Recent data do not support a clear association between continuation or discontinuation of APAs and rates of ischemic events, bleeding complications, and mortality up to 6 months after surgery. Clinical factors, such as indication and urgency of the operation, time since stent placement, invasiveness of the procedure, preoperative cardiac optimization, underlying functional status, as well as perioperative control of supply-demand mismatch and bleeding may be more responsible for adverse outcome than antiplatelet management. SUMMARY: Perioperative management of antiplatelet therapy (APT) should be individually tailored based on consensus among the anesthesiologist, cardiologist, surgeon, and patient to minimize both ischemic/thrombotic and bleeding risks. Where possible, surgery should be delayed for a minimum of 1 month but ideally for 3-6 months from the index cardiac event. If bleeding risk is acceptable, dual APT (DAPT) should be continued perioperatively; otherwise P2Y12 inhibitor therapy should be discontinued for the minimum amount of time possible and aspirin monotherapy continued. If bleeding risk is prohibitive, both aspirin and P2Y12 inhibitor therapy should be interrupted and bridging therapy may be considered in patients with high thrombotic risk.

Mitral Valve Replacement with Thymectomy in a Patient with Ocular Myasthenia Gravis: Case Report.

Patients diagnosed with ocular myasthenia gravis (MG) and mitral valve disease represent a significant perioperative management problem, especially for the anaesthesiologist, due to complex inter-actions between the disease, drugs to treat the disease, and anaesthetic agents, such as neuromuscu-lar blocking agents (NMBAs). This paper describes the successful management of a 31-year-old female with mitral valve stenosis and ocular MG who was diagnosed with MG 4 years prior to the indication for cardiac surgery. Preoperatively, the patient was under treatment with Pyridostigmine and Prednisone. Mitral valve replacement and full thymectomy were performed, under general anaesthesia, using Fentanyl, Sevoflurane and low doses of non-depolarising NMBAs. The postoperative course was uneventful, the patient was extubated at 6 hours postoperatively, in-tensive care unit stay was 48 hours, and the patient was discharged after 6 days without any compli-cations. After 3 months, at the follow-up examination, the patient's ocular symptoms (eyelid ptosis) disappeared.

Giant Aortic Syphilitic Aneurysm of The Ascending Aorta with Erosion in the Chest Wall: Case Report.

Since the discovery of penicillin, the incidence of tertiary syphilis dramatically has decreased. However, cases of cardiovascular complications of syphilis still are present. Ascending aortic aneurysms are some of the most devastating complications. Nonetheless, syphilitic aortitis (SA) can appear and should be suspected in patients with syphilis and aortic aneurysm. We report a case of a 57-year-old patient with a large ascending aortic aneurysm with cartilage and rib erosion. The purpose of this article is to discuss the particular surgical aspects of this unusual case.

Successful Management of Unremitting Spasm after Myocardial Revascularization Exclusively with Bilateral Internal Thoracic Arteries in Y-graft Configuration: A Case Report.

Coronary artery spasm (CAS) after coronary artery bypass grafting (CABG) is rare, and in time may be fatal for the patient if undiagnosed. The purpose of the present study is to report the case of a patient who survived after experiencing a persistent spasm of all native coronary arteries following successful arterial myocardial revascularization. Furthermore, we aimed to discuss the therapeutic strategies which may prevent the occurrence of a coronary artery spasm in settings of myocardial revascularization, in the context of reviewed specific literature evidences.

Options in Targeted Therapy for Advanced Cholangiocarcinoma: A 2024 Update.

Bile duct carcinomas have a different prognosis and genetic profile depending on their location; intrahepatic/extrahepatic or at the level of the gallbladder. Although in recent years there have been important advances in first-line therapy, second-line therapy in cholangiocarcinoma does not currently have a standard. Therefore at this level, there is an acute need for personalized treatment. The present article is a narrative review that aims to list the newest targeted therapeutic options for this type of cancer, based on identified genetic alterations. The literature selected for analysis includes phase 2 or 3 studies with targeted therapy in this disease and original articles no older than three years that describe the prevalence of the most common gene alterations in this type of cancer. PubMed/Medline, Scopus, and Clarivate-Web of Science databases were searched and keywords such as "cholangiocarcinoma," "biliary cancer," "targeted therapy," "gene amplifications," and "mutations" were used. This narrative review was designed taking into account the SANRA (Scale for the Assessment of Narrative Review Articles) criteria. The conclusions lead to the fact that next-generation sequencing testing is of particular usefulness in cholangiocarcinoma. Bile duct cancers are rich in targetable genetic alterations, and their treatment is in constant change, although much of the current data comes from phase II studies. There is a great need for the current options to be analyzed in phase III studies. Hence, the need of the oncological community to stay informed about targeted treatment options for cholangiocarcinoma is supported by the present article.

Acute Promyelocytic Leukemia and Severe Differentiation Syndrome in Pregnancy-A Management Challenge.

Acute promyelocytic leukemia (APL) is generated by the PML-RARA fusion gene. In patients suffering from APL, the early diagnosis and treatment are essential in the successful management. We reported a case of a 27-year-old 17th-week pregnant patient diagnosed with APL. After an extensive hematological diagnostic panel, the acute promyelocytic leukemia was confirmed, and the patient received all-trans retinoic acid (ATRA), idarubicin (IDA), and dexamethasone, following national guidelines. Due to ATRA-related differentiation syndrome, the therapy was adjusted, and hydroxycarbamide was added with a good outcome. The patient was admitted to the ICU secondary to hypoxemic respiratory failure on the 2nd day after hospital admission. Our patient received an individualized drug combination, adjusted by the clinical response. Furthermore, the drugs used in APL treatment are all teratogenic. Despite various major complications, including severe acute respiratory distress syndrome (ARDS), which needed mechanical ventilation; ICU-acquired myopathy; and spontaneous abortion, the patient had a good outcome and was transferred from the ICU after a total stay of 40 days. APL during pregnancy is a rare entity of intermediate-risk APL. Our study emphasized the need for individualized therapy in a rare case of a pregnant woman diagnosed with a potentially fatal hematologic disease.

Human health risk assessment of potentially toxic elements and microplastics accumulation in products from the Danube River Basin fish market.

The present study aimed to quantify the concentration levels of potentially toxic elements (PTEs) such as aluminum, arsenic, cadmium, chromium, copper, nickel, lead, zinc, and mercury, as well as microplastics occurrence in various tissues of fish and seafood species, commercialized in the Lower Danube River Basin. A health risk assessment analysis was performed based on the PTEs concentration levels in the muscle tissue. Estimated daily intake (EDI), target hazard quotient (THQ), hazard index (HI), and target cancer risk (TR) of PTEs were calculated. It was observed that the species within the seafood category registered the highest levels of PTEs. For instance, in the muscle tissue of bivalve Mytilus galloprovincialis (from the Black Sea), the highest value was observed in the case of Zn (37.693 mg/kg), and the presence of polystyrene polymer was identified. The values associated with EDI, THQ, HI, and TR of PTE exposure were significantly lower than 1.

ICU-Associated Costs during the Fourth Wave of the COVID-19 Pandemic in a Tertiary Hospital in a Low-Vaccinated Eastern European Country.

The COVID-19 pandemic has been associated with a tremendous financial and social impact. The pressure on healthcare systems worldwide has increased with each pandemic wave. The present study assesses the impact of the COVID-19 pandemic on healthcare-derived costs of critically ill patients during the fourth wave of the COVID-19 pandemic in a tertiary hospital in Romania. We prospectively included patients admitted to a single-centre intensive care unit (ICU) during the fourth wave of the COVID-19 pandemic. Median daily costs were calculated from financial records and divided in three groups: administrative costs, treatment costs and investigation costs. These were then compared to two retrospective cohorts of non-COVID-19 patients admitted to the same ICU during the same time interval in 2020 and 2019. Demographic data and the management of SARS-CoV-2 infection and of associated organ dysfunctions were recorded to identify risk factors for higher costs. Our results show that the COVID-19 pandemic has been associated with a 70.8% increase in total costs compared to previous years. This increase was mainly determined by an increase in medication and medical-device-related costs. We identified the following as risk factors for increased costs: higher degrees of lung involvement, severity of respiratory dysfunction, need for renal replacement therapy and the use of antiviral or immunomodulatory therapy. Costs were higher in patients who had a shorter duration of hospitalization. In conclusion, the COVID-19 pandemic is associated with increased costs for patients, and rapid measures need to be taken to ensure adequate financial support during future pandemic waves, especially in developing countries.

Outcomes of COVID-19 Critically Ill Extremely Elderly Patients: Analysis of a Large, National, Observational Cohort.

BACKGROUND: During the COVID-19 pandemic, resource allocation became a major problem in globally overwhelmed ICUs. The main goal of this study was to describe the clinical characteristics of the very elderly patients (aged ≥ 80 years) with COVID-19 admitted in Romanian ICUs. The study objectives were to evaluate and determine the factors associated with ICU mortality. METHODS: We designed a national, multicentric, observational platform with prospective enrolment. This study included patients aged ≥ 80 years admitted in Romanian ICUs with SARS-CoV-2 infection from March 2020 to December 2021. RESULTS: We included 1666 patients with a median age of 83 years and 78% ICU mortality. Male sex, dyspnoea, lower Glasgow Coma Scale and lower SpO2 at ICU admission, the need for mechanical ventilation (MV), and corticosteroid use were independently associated with mortality. A total of 886/1666 (53%) elderly patients underwent invasive mechanical ventilation, with a mortality of 97%. The age impact on mortality was confirmed by a 1:1 propensity matching with less elderly ICU patients. CONCLUSION: In extremely elderly patients with COVID-19 admitted in the ICU, mortality is high, particularly when requiring MV. Therapy should be directed towards the optimization of less invasive ventilatory methods and the use of MV and corticosteroids only in highly selected patients.

Sex and gender differences in anesthesia: Relevant also for perioperative safety?

Sex (a biological determination) and gender (a social construct) are not interchangeable terms and both impact perioperative management and patient safety. Sex and gender differences in clinical phenotypes of chronic illnesses and risk factors for perioperative morbidity and mortality are relevant for preoperative evaluation and optimization. Sex-related differences in physiology, as well as in pharmacokinetics and pharmacodynamics of anesthetic drugs may influence the anesthesia plan, the management of pain, postoperative recovery, adverse effects, patient satisfaction, and outcomes. Further studies are needed to characterize outcome differences between men and women in non-cardiac, cardiac, and transplantation surgery in order to individualize perioperative management and improve patient safety. Transgender patients represent a vulnerable population who need special perioperative care. Gender balance increases team performance and may improve perioperative outcomes.

Preliminary investigation of lower Danube pollution caused by potentially toxic metals.

The current study aims to assess the pollution status of the European river-sea system lower Danube River-Danube Delta-North West Black Sea, through an integrated analysis of metal concentrations in water, sediments and fish community. The Danube flows through numerous industrial cities and receives a significant amount of pollutants due to the reception of urban and industrial emissaries, as well as agricultural land runoff. Samples of water, sediments and fish (10 species) were collected from 7 representative sites along Danube River, Danube Delta and Black Sea shore. For the analysed fish species, potentially toxic and essential elements (Pb, Cd, As, Cu, Fe, Zn, Mg, Ca, Na, K) from muscle and liver samples were measured and discussed. Measurement of elements and other environmental quality parameters were determined for water and sediments. The Black Sea area, represented by S6 and S7, received sediments from Danube with the lowest concentrations of Cd (0.05 ± 0.01 µg g-1, respectively 0.01 ± 0.001 µg g-1), Pb (3 ± 0.03 µg g-1, respectively 2 ± 0.03 µg g-1), As (2 ± 0.02 µg g-1, respectively 1.4 ± 0.3 µg g-1), Ni (8.9 ± 0.1 µg g-1, respectively 5.2 ± 0.2 µg g-1), Cr (8 ± 0.7 µg g-1, respectively 5 ± 0.2 µg g-1), Cu (3 ± 0.1 µg g-1, respectively 2 ± 0.04 µg g-1), Fe(6 ± 0.3 µg g-1, respectively 3 ± 0.1 µg g-1) and Zn (0.03 ± 0.003 µg g-1, respectively 0.017 ± 0.001 µg g-1). These results suggest that the Danube Delta system plays an important role in filtering the pollutants. Based on the biota and water analysis, there was no correlation observed between Cd, respectively Pb concentration in the environment and fish body (Person Coef. = -0.02 in muscle tissue and -0.01 in liver tissue, respectively Pearson Coeff. = -0.06 in muscle tissue and 0.1 in liver tissue). Cadmium remained an active element in the pollution of the Danube area (S1 and S2), with high concentration in the water matrix (0.14 ± 0.02 µg L-1, respectively 0.05 ± 0.01 µg L-1) and fish muscle (0.15 ± 0.03 µg g-1f.w. in C. carpio - S2). This fact was confirmed by several other studies.

Role of Anaesthetic Choice in Improving Outcome after Cardiac Surgery.

CLINICAL BACKGROUND: Volatile anaesthetics (VAs) have been shown to protect cardiomyocytes against ischaemia and reperfusion injury in cardiac surgery. CLINICAL PROBLEMS: VAs have been shown in multiple trials and meta-analyses to be associated with better outcomes when compared to intravenous anaesthesia in cardiac surgery. However, recent data from a large randomised controlled trial do not confirm the superiority of VA as compared to total intravenous anaesthesia in this population. REVIEW OBJECTIVES: This mini review presents the VA cardioprotective effects, their clinical use in cardiac surgery and the most recent evidence that compares VA to intravenous anaesthesia for reducing perioperative morbidity. At present, there is no clear superiority of VA over intravenous anaesthesia in improving the outcome after cardiac surgery.

Extracorporeal Membrane Oxygenation (ECMO) Rescue Therapy in Post-cardiotomy Cardiogenic Shock: A Case Report.

Cardiogenic shock is a constant challenge for the intensivist when complicating a myocardial infarction, due to the high rate of associated morbidity and mortality, especially in the setting of mechanical complications such as papillary muscle rupture. We present the case of a 49-year-old woman with cardiogenic shock due to acute myocardial infarction (AMI) complicated by severe mitral valve insufficiency due to papillary muscle rupture. She was treated initially by medical optimization, followed by mitral valve replacement and complete surgical revascularization, requiring rescue mechanical circulatory support by extracorporeal membrane oxygenation (ECMO). ECMO proved to be a rescue therapy in a patient with refractory cardiogenic shock after urgent cardiac surgery.

New FDA approved antibacterial drugs: 2015-2017.

Increasing bacterial resistance to antibiotics is a worldwide ongoing issue. Urgent need for new antibacterial agents has resulted in significant research efforts, with new molecules proposed for use in clinical practice. However, as highlighted by many groups this process does not have an optimal rhythm and efficacy, to fully combat highly adaptive germs, particularly in the intensive care units. This review focuses on the last three years of novel FDA approved antibacterial agents (2015-2017): ceftazidime/avibactam, obiltoxaximab, bezlotoxu-mab, delafloxacin, meropenem/vaborbactam, ozenoxacin. Ceftazidime/avibactam and meropenem/ vaborbactam are new players in the field of resistant bacteria treatment. Ceftazidime/avibactam is validated in selected patients with complicated urinary or intra-abdominal infections, hospital and ventilator-associated pneumonia. Meropenem/ vaborbactam gained approval for the cases of complicated urinary tract infections. Other potential indications are under investigation, widened and validated by future studies. Obiltoxaximab is a monoclonal antibody that can be used in the prevention and treatment of inhalational anthrax. Bezlotoxumab monoclonal antibody is an useful and specific tool for the management of recurrent Clostridium difficile infection. Delafloxacin is approved for patients with acute skin or skin structure infections. Despite recent progress, it is imperative to continue the development of new antibiotic drugs and new strategies to counteract resistance to antibiotics.

Anaesthesiology trainees and their needs: a Romanian perspective. Results from a European survey.

Anaesthesiology training is going through continuous transformations worldwide. Recent data from a European Survey on anaesthesiology postgraduate trainees and their concerns have been published for the first time, following an initiative by the European Society of Anaesthesiology. Among the responders of this survey, 10.8% were represented by Romanian trainees. The main needs of the Romanian anaesthesiology trainees who completed the questionnaire were, in descending order educational contents/EDAIC, technical skills, exchange programmes, residency workload, residency costs and autonomy transition. Another observation coming from the analysed data is that Romanian anaesthesiologists in training are highly concerned and interested in the field of intensive care medicine. The results also pinpoint to the high costs associated with continuous medical education, leading to a high incentive for workforce migration.

Perioperative Patient Blood Management Programme. Multidisciplinary recommendations from the Patient Blood Management Initiative Group.

Patients with untreated anaemia or iron deficiency who undergo surgical procedures have an increased risk for mortality and morbidity. Patient Blood Management programmes address this issue worldwide and try to improve patient outcomes through a complex set of measures targeting anaemia correction, minimisation of bleeding and improvement of anaemia tolerance, in all phases of perioperative care. The Patient Blood Management Initiative Group is a multidisciplinary team of physicians from specialties including anaesthesiology, nephrology, surgery, orthopaedics, haematology, gastroenterology and transfusion medicine. The team has elaborated ten recommendations, divided into five categories, in order to implement a Patient Blood Management programme in Romania, using the most recent and relevant evidence. The document was discussed during three meetings which took place during October 2016 and May 2017 and the result was modified and updated via e-mail.