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Antimicrobial resistance (AMR) has emerged as one of the leading public health threats of the 21st century. New evidence underscores its significance in patients' morbidity and mortality, length of stay, as well as healthcare costs. Globally, the factors that contribute to antimicrobial resistance include social and economic determinants, healthcare governance, and environmental interactions with impact on humans, plants, and animals. Antimicrobial stewardship (AS) programs have historically overlooked surgical teams as they considered them more difficult to engage. This review aims to summarize the evolution and significance of AS in surgical wards, including the surgical intensive care unit (SICU) and the role of diagnostic stewardship (DS). The contribution of AS team members is presented. The new diagnostic modalities and the new technologies including artificial intelligence (AI) are also reviewed.
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ABSTRACT: We aimed to evaluate heparin-binding protein (HBP) as a marker of prognosis of unfavorable outcome in COVID-19 pneumonia. This was a post hoc analysis of the SAVE clinical trial investigating anakinra treatment, guided by suPAR (soluble urokinase plasminogen activator receptor) levels ≥6 ng/mL, for the prevention of severe respiratory failure in hospitalized patients with COVID-19 pneumonia. Baseline HBP plasma levels were measured in 534 patients by fluorescence dry quantitative immunoassay using the Jet-iStar 800 analyzer. Concentrations higher than 35 ng/mL predicted 30-day mortality with a moderate specificity of 53.3% and negative predictive value 78.1%; sensitivity was low (29.0%). After multivariate Cox analysis, HBP higher than 35 ng/mL was an independent predictor of 30-day unfavorable outcome (adjusted hazard ratio, 1.77; 95% CI, 1.06-2.94; P = 0.028) and these patients were also at greater risk of death after 90 days (hazard ratio, 1.85; 95% CI, 1.25-2.74; P = 0.002). The cutoff was not predictive of development of severe respiratory failure, septic shock or acute kidney injury. Among patients with baseline HBP levels higher than 35 ng/mL, anakinra treatment was associated with decreased mortality (7.2%) versus comparators (18.1%; P < 0.001). Results confirm that HBP may be an early biomarker of poor outcome among preselected patients at risk from COVID-19 pneumonia.ClinicalTrials.gov registration NCT04357366.
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Peptídeos Catiônicos Antimicrobianos , Proteínas Sanguíneas , COVID-19 , Insuficiência Respiratória , Humanos , Biomarcadores , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , PrognósticoRESUMO
BACKGROUND: Endotype classification may guide immunomodulatory management of patients with bacterial and viral sepsis. We aimed to identify immune endotypes and transitions associated with response to anakinra (human interleukin 1 receptor antagonist) in participants in the SAVE-MORE trial. METHODS: Adult patients hospitalized with radiological findings of PCR-confirmed severe pneumonia caused by SARS-CoV-2 and plasma-soluble urokinase plasminogen activator receptor levels of ≥ 6 ng/ml in the SAVE-MORE trial (NCT04680949) were characterized at baseline and days 4 and 7 of treatment using a previously defined 33-messenger RNA classifier to assign an immunological endotype in blood. Endpoints were changes in endotypes and progression to severe respiratory failure (SRF) associated with anakinra treatment. RESULTS: At baseline, 23.2% of 393 patients were designated as inflammopathic, 41.1% as adaptive, and 35.7% as coagulopathic. Only 23.9% were designated as the same endotype at days 4 and 7 compared to baseline, while all other patients transitioned between endotypes. Anakinra-treated patients were more likely to remain in the adaptive endotype during 7-day treatment (24.4% vs. 9.9%; p < 0.001). Anakinra also protected patients with coagulopathic endotype at day 7 against SRF compared to placebo (27.8% vs. 55.9%; p = 0.013). CONCLUSION: We identify an association between endotypes defined using blood transcriptome and anakinra therapy for COVID-19 pneumonia, with anakinra-treated patients shifting toward endotypes associated with a better outcome, mainly the adaptive endotype. Trial registration ClinicalTrials.gov, NCT04680949, December 23, 2020.
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COVID-19 , Pneumonia , Adulto , Humanos , SARS-CoV-2 , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Pneumonia/tratamento farmacológico , TranscriptomaRESUMO
BACKGROUND: Pneumonia and bloodstream infections (BSI) due to extensively drug-resistant (XDR) Acinetobacter baumannii, XDR Pseudomonas aeruginosa, and carbapenem-resistant Enterobacterales (CRE) are associated with high mortality rates, and therapeutic options remain limited. This trial assessed whether combination therapy with colistin and meropenem was superior to colistin monotherapy for the treatment of these infections. METHODS: The OVERCOME (Colistin Monotherapy versus Combination Therapy) trial was an international, randomized, double-blind, placebo-controlled trial. We randomly assigned participants to receive colistin (5 mg/kg once followed by 1.67 mg/kg every 8 hours) in combination with either meropenem (1000 mg every 8 hours) or matching placebo for the treatment of pneumonia and/or BSI caused by XDR A. baumannii, XDR P. aeruginosa, or CRE. The primary outcome was 28-day mortality, and secondary outcomes included clinical failure and microbiologic cure. RESULTS: Between 2012 and 2020, a total of 464 participants were randomly assigned to treatment, and 423 eligible patients comprised the modified intention-to-treat population. A. baumannii was the predominant trial pathogen (78%) and pneumonia the most common index infection (70%). Most patients were in the intensive care unit at the time of enrollment (69%). There was no difference in mortality (43 vs. 37%; P=0.17), clinical failure (65 vs. 58%; difference, 6.8 percentage points; 95% confidence interval [CI], -3.1 to 16.6), microbiologic cure (65 vs. 60%; difference, 4.8 percentage points; 95% CI, -5.6 to 15.2), or adverse events (acute kidney injury, 52 vs. 49% [P=0.55]; hypersensitivity reaction, 1 vs. 3% [P=0.22]; and neurotoxicity, 5 vs. 2% [P=0.29]) between patients receiving monotherapy and combination therapy, respectively. CONCLUSIONS: Combination therapy with colistin and meropenem was not superior to colistin monotherapy for the treatment of pneumonia or BSI caused by these pathogens. (Funded by the National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases protocol 10-0065; ClinicalTrials.gov number, NCT01597973.).
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In our hospital, adherence to the guidelines for peri-operative antimicrobial prophylaxis (PAP) is suboptimal, with overly long courses being common. This practice does not offer any incremental benefit, and it only adds to the burden of antimicrobial consumption, promotes the emergence of antimicrobial resistance, and it is associated with adverse events. Our objective was to study the effect of an electronic reminder on the adherence to each element of PAP after cardiac surgery. We conducted a single center, before and after intervention, prospective cohort study from 1 June 2014 to 30 September 2017. The intervention consisted of a reminder of the hospital guidelines when ordering PAP through the hospital information system. The primary outcome was adherence to the suggested duration of PAP, while secondary outcomes included adherence to the other elements of PAP and incidence of surgical site infections (SSI). We have studied 1080 operations (400 pre-intervention and 680 post-intervention). Adherence to the appropriate duration of PAP increased significantly after the intervention [PRE 4.0% (16/399) vs. POST 15.4% (105/680), chi-square p < 0.001]; however, it remained inappropriately low. Factors associated with inappropriate duration of PAP were pre-operative hospitalization for <3 days, and duration of operation >4 h, while there were significant differences between the chief surgeons. Unexpectedly, the rate of SSIs increased significantly during the study (PRE 2.8% (11/400) vs. POST 5.9% (40/680), chi-square p < 0.019). The implemented intervention achieved a relative increase in adherence to the guideline-recommended PAP duration; however, adherence was still unacceptably low and further efforts to improve adherence are needed.
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Cytomegalovirus (CMV) infection/disease has been repeatedly reported in patients treated with immune-checkpoint inhibitors (ICIs) and most commonly involves patients with relapsed/refractory (R/R) immune-related adverse events (irAEs). In the current study, we present a patient with melanoma who developed CMV gastritis during treatment with pembrolizumab in the absence of irAEs and without previous or current immunosuppression. Moreover, we review the literature regarding CMV infection/disease in patients treated with ICIs for solid malignancies. We present the currently available data on the pathogenesis, clinical characteristics, endoscopic findings, and histologic features and highlight the potential differences among cases complicating R/R irAEs versus those occurring in patients who are immunosuppression naive. Finally, we discuss the currently available data regarding potential useful diagnostic tools as well as the management of these patients.
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Background: The SAVE-MORE trial demonstrated that anakinra treatment in COVID-19 pneumonia with plasma soluble urokinase plasminogen activator (suPAR) levels of 6 ng/mL or more was associated with 0.36 odds for a worse outcome compared to placebo when expressed by the WHO-Clinical Progression Scale (CPS) at day 28. Herein, we report the results of subgroup analyses and long-term outcomes. Methods: This prospective, double-blind, randomised clinical trial, recruited patients with a confirmed SARS-CoV-2 infection, in need of hospitalisation, lower respiratory tract infection and plasma suPAR ≥6 ng/mL from 37 academic and community hospitals in Greece and Italy. Patients were 1:2 randomised to subcutaneous treatment with placebo or anakinra (100 mg) once daily for 10 days. Pre-defined subgroups of Charlson's comorbidity index (CCI), sex, age, level of suPAR, and time from symptom onset were analysed for the primary endpoint (overall comparison of distribution of frequencies of the scores from the WHO-CPS between treatments on day 28), by multivariable ordinal regression analysis in the intention to treat (ITT) population. This trial is registered with the EU Clinical Trials Register (2020-005828-11) and ClinicalTrials.gov (NCT04680949). Findings: Patients were enrolled between 23 December 2020 and 31 March 2021; 189 patients in the placebo arm and 405 patients in the anakinra arm were the ITT population. Multivariable analysis showed that anakinra treatment was accompanied by significantly lower odds for worse outcome compared to placebo at day 28 for all studied subgroups (CCI ≥ 2, OR: 0.34, 95% confidence intervals [CI] 0.22-0.50; CCI < 2, OR: 0.38, 95% CI 0.21-0.68; suPAR > 9 ng/mL, OR: 0.35, 95% CI 0.19-0.66; suPAR 6-9 ng/mL, OR: 0.35, 95% CI 0.24-0.52; patients ≥65 years, OR: 0.41, 95% CI 0.25-0.66; and patients <65 years, OR: 0.29, 95% CI 0.19-0.45). The benefit was uniform, irrespective of the time from start of symptoms until the start of the study drug. At days 60 and 90, anakinra treatment had odds of 0.40 (95% CI 0.28-0.57) and 0.46 (95% CI 0.32-0.67) respectively, for a worse outcome compared to placebo. The costs of general ward stay, ICU stay, and drugs were lower with anakinra treatment. Interpretation: Anakinra represents an important therapeutic tool in the management of COVID-19 that may be administered in all subgroups of patients; benefits are maintained until day 90. Funding: Hellenic Institute for the Study of Sepsis; Swedish Orphan Biovitrum AB.
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OBJECTIVES: Elevated concentrations of soluble urokinase plasminogen activator receptor (suPAR) predict progression to severe respiratory failure (SRF) or death among patients with COVID-19 pneumonia and guide early anakinra treatment. As suPAR testing may not be routinely available in every health-care setting, alternative biomarkers are needed. We investigated the performance of C-reactive protein (CRP), interferon gamma-induced protein-10 (IP-10) and TNF-related apoptosis-inducing ligand (TRAIL) for predicting SRF or death in COVID-19. METHODS: Two cohorts were studied; one discovery cohort with 534 patients from the SAVE-MORE clinical trial; and one validation cohort with 364 patients from the SAVE trial including also 145 comparators. CRP, IP-10 and TRAIL were measured by the MeMed Key® platform in order to select the biomarker with the best prognostic performance for the early prediction of progression into SRF or death. RESULTS: IP-10 had the best prognostic performance: baseline concentrations 2000 pg/ml or higher predicted equally well to suPAR (sensitivity 85.0 %; negative predictive value 96.6 %). Odds ratio for poor outcome among anakinra-treated participants of the SAVE-MORE trial was 0.35 compared to placebo when IP-10 was 2,000 pg/ml or more. IP-10 could divide different strata of severity for SRF/death by day 14 in the validation cohort. Anakinra treatment decreased this risk irrespective the IP-10 concentrations. CONCLUSIONS: IP-10 concentrations of 2,000 pg/ml or higher are a valid alternative to suPAR for the early prediction of progression into SRF or death the first 14 days from hospital admission for COVID-19 and they may guide anakinra treatment. CLINICALTRIALS: gov, NCT04680949 and NCT04357366.
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COVID-19 , Insuficiência Respiratória , Humanos , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Interferon gama , Quimiocina CXCL10 , Proteína Antagonista do Receptor de Interleucina 1 , Prognóstico , Biomarcadores , Proteína C-ReativaRESUMO
We conducted a single-center, non-interventional retrospective study of melanoma patients with COVID-19 (1 March 2020 until 17 March 2023). The cohort was further divided into three groups according to the periods of SARS-CoV-2 variant dominance in Greece. We recorded demographics, comorbidities, vaccination data, cancer diagnosis/stage, types of systemic melanoma treatments, date of COVID-19 diagnosis and survival. We identified 121 patients. The vast majority (87.6%) had advanced disease (stages III or IV). A total of 80.1% of the patients were receiving immune checkpoint inhibitor-based therapies, 92.5% had asymptomatic/mild COVID-19 and 7.4% had moderate/severe/critical disease, while 83.5% contracted COVID-19 during the third period of the pandemic. Sixteen patients (13.2%) were hospitalized for COVID-19 with a median length of stay of 12 days (range: 1-55 days). Advanced age, heart failure, number of comorbidities (≤1 vs. >1), vaccination status and the time period of the infection correlated with more severe COVID-19, whereas only heart failure and time period were independently correlated with severity. The 30-day mortality rate after COVID-19 was 4.2%. With a median follow-up of 340 days post-COVID-19, 17.4% of patients were deceased. In this cohort of melanoma patients with COVID-19, the 30-day mortality rate was low. There was no association between melanoma stage, treatment receipt and type of treatment with COVID-19 severity.
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OBJECTIVES: Carbapenemase-producing Enterobacterales (CPE) comprise important nosocomial pathogens worldwide. Colonized patients are the source of further dissemination in healthcare settings. Considering that timely detection of CPE carriers is pivotal but universal screening is unfeasible, we aimed to develop and validate a prediction score to detect patients harbouring CPE on hospital admission. METHODS: The study was conducted in a tertiary care hospital located in a CPE endemic area. Rectal swabs were obtained from 2303 patients, screened shortly after hospital admission. The Enterobacterales isolated in cultures were examined for the presence of blaVIM, KPC, NDM, OXA-48 by PCR. Demographic data and patient history of the previous 6 months were recorded. Risk factors for CPE carriage were identified using a multivariable logistic regression model and a points-system risk score was developed. The discriminative ability of the risk score was assessed using the AUC and its predictive performance was validated in a second dataset of 1391 patients in a different time period. RESULTS: Seven predictors were identified: previous CPE colonization or infection, prior hospitalization, stay in a long-term health care facility, history of ≥2 interventions, renal replacement therapy, diabetes with end-organ damage and Karnofsky score. The developed risk score in the derivation dataset ranged between 0 and 79 points, with an AUC of 0.84 in the derivation and 0.85 in the validation dataset. CONCLUSIONS: This prediction tool may assist in identifying patients who are at risk of harbouring CPE on hospital admission in an endemic area and guide clinicians to implement prompt and appropriate infection control measures.
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Infecções por Enterobacteriaceae , Humanos , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/diagnóstico , Centros de Atenção Terciária , beta-Lactamases/análise , Proteínas de Bactérias/genética , Proteínas de Bactérias/análise , HospitalizaçãoRESUMO
Coronavirus disease 2019 (COVID-19) is a systemic illness with an increased host inflammatory response that affects multiple extra-pulmonary organs, including the gastrointestinal tract. Abnormalities in liver biochemistry have been observed in a significant proportion of patients with COVID-19 upon admission, and this proportion increases with hospitalization. These abnormalities are typically manifested as elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, with less frequently detected elevations in the levels of cholestatic enzymes. Elevated aminotransaminase levels have been linked to an increased risk of mortality and complications, indicating the severity of COVID-19 infection. The present study evaluated the prevalence and the baseline factors associated with the development of acute hepatitis (ΑΗ), liver injury (LI) and associated patterns, as well as the presence of abnormalities in the levels of aminotransferases at discharge in the same cohort. For this purpose, 1,304 patients with confirmed COVID-19 infection were enrolled in the study. According to the results obtained, AST levels at baseline were the only independent factor for AH during hospital stay, while AST, alkaline phosphatase and ferritin levels were independent baseline factors for the development of LI. The patients with hepatocellular, compared to those with cholestatic LI, exhibited similar survival rates, as well as similarities in the development of acute kidney injury and the need for oxygen via high-flow nasal cannula and/or mechanical ventilation. In addition, age and ALT were independent risk factors for persistent abnormal values of AST and ALT at discharge.
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BACKGROUND: Although several liver- and inflammation-based scores to predict the clinical course of patients with coronavirus disease 2019 (COVID-19) have been evaluated, no direct comparison regarding their predictive ability has been performed. METHODS: 1038 patients (608 males, age 63.5 ± 17 years) hospitalized with documented COVID-19 infection to the non-ICU ward, were included retrospectively. Clinical and laboratory characteristics on admission including evaluation of Fibrosis-4 (FIB-4) score and C-Reactive Protein (CRP) to albumin ratio (CAR) were recorded. RESULTS: One hundred and twenty-four patients (11.9%) died during hospitalization after 8 (3-72) days. In multivariate analysis, FIB-4 (hazard ratio, 1.11; 95% confidence interval (CI), 1.034-1.19; P = 0.004), was independently associated with mortality, with very good discriminative ability (area under the receiver operating characteristic curve curve, 0.76). The patients with FIB-4 >2.67 (n = 377), compared to those with ≤2.67 (n = 661), had worse survival (log-rank 32.6; P < 0.001). Twenty-four (6.8%) of 352 patients with possible nonalcoholic fatty liver disease (NAFLD) (defined as Hepatic Steatosis Index >36) died during hospitalization. In multivariate analysis, CAR was an independent risk factor (1) for mortality (hazard ratio, 1.014; 95% CI, 1.002-1.025; P = 0.021), (2) the need for high-flow nasal cannula with or without intubation (hazard ratio, 1.016; 95% CI, 1.004-1.027; P = 0.007) and (3) development of acute kidney injury (hazard ratio, 1.017; 95% CI, 1.006-1.028; P = 0.002). In addition, the patients with possible NAFLD and CAR >12 (n = 154), compared to those with CAR ≤12 (n = 198), had worse survival (log-rank 5.1; P = 0.024). CONCLUSIONS: FIB-4 was an independent factor for mortality with better performance compared to other liver function test- and inflammation-based scores in patients with COVID-19, while CAR was the only score independently associated with the clinical course in COVID-19 patients with possible NAFLD.
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COVID-19 , Hepatopatia Gordurosa não Alcoólica , Idoso , Idoso de 80 Anos ou mais , Albuminas , Proteína C-Reativa , Fibrose , Humanos , Inflamação/complicações , Cirrose Hepática/complicações , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Prognóstico , Estudos RetrospectivosRESUMO
(1) Background: It is not known whether different daily dosing schemes have different effects on colistin nephrotoxicity. We examined the effect of once- versus twice- or thrice-daily doses of colistin on renal function. (2) Methods: We performed a multicenter retrospective cohort study of hospitalized patients with a baseline glomerular filtration rate ≥ 50 mL/min who received intravenously the same colistin dose once (regimen A), twice (regimen B) or thrice daily (regimen C). The primary endpoint was acute kidney injury (AKI), defined as fulfilment of any of the RIFLE (Risk-Injury-Failure-Loss-End stage renal disease) criteria. (3) Results: We included 306 patients; 132 (43.1%) received regimen A, 151 (49.3%) regimen B, and 23 (7.5%) regimen C. Ninety-nine (32.4%) patients developed AKI; there was no difference between regimen A vs. B and C [45 (34.1%) vs. 54 (31.0%), p = 0.57]. In a propensity score−matched cohort, AKI was similar in patients receiving Regimen A, Regimen B, and Regimen C (31.6% vs. 33.3%, p = 0.78). On logistic regression analysis, diabetes was an independent predictor of AKI (OR = 4.59, 95% CI 2.03−10.39, p = 0.001) while eGFR > 80 mL/min (OR = 0.50, 95% CI 0.25−0.99, p = 0.048) was inversely associated with AKI. (4) Conclusions: Colistin once daily is not more nephrotoxic than the standard colistin regimens. The only independent predictor of nephrotoxicity was diabetes mellitus, while eGFR > 80 mL/min had a protective effect.
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The exact impact of immune checkpoint inhibitors in the course and outcome of COVID-19 in cancer patients is currently unclear. Herein, we present the first description of an elderly melanoma patient who developed COVID-19 pneumonia while under treatment with nivolumab and bempegaldesleukin in combination with an investigational PEGylated interleukin (IL-2). We present the clinical characteristics and the laboratory and imaging findings of our patient during the course of COVID-19 pneumonia. Moreover, we discuss the currently available data regarding the mechanism of action of immune checkpoint inhibitors and IL-2 analogs in the treatment of COVID-19. The administration of these agents did not have a negative effect on the outcome of COVID-19 pneumonia in an elderly melanoma patient.
Immune checkpoint inhibitors represent a major advance in the treatment of several solid malignancies, including melanoma. Bempegaldesleukin is an investigational PEGylated IL-2 that is being evaluated, in combination with nivolumab, in the management of a variety of cancers. The immunomodulation caused by these agents may also modify the immune response in COVID-19. Currently available data regarding the impact of immune checkpoint inhibitors in reducing the severity of COVID-19 in patients with cancer are mixed, whereas no clinical data are available for bempegaldesleukin. Herein, we report the case of an elderly female melanoma patient who developed COVID-19 pneumonia while under treatment with nivolumab and bempegaldesleukin. The administration of these agents did not have a negative effect on the outcome of COVID-19 pneumonia in our patient.
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Tratamento Farmacológico da COVID-19 , Melanoma , Idoso , Humanos , Inibidores de Checkpoint Imunológico , Interleucina-2/uso terapêutico , Melanoma/complicações , Melanoma/tratamento farmacológico , Nivolumabe/uso terapêuticoRESUMO
Background: Abnormalities in aminotransferases are frequently observed in hospitalized COVID-19 patients, but their clinical impact is poorly characterized. Methods: A total of 1046 patients hospitalized to the non-intensive care unit ward with documented COVID-19 were included retrospectively. Demographic, clinical and laboratory characteristics on admission and during hospital stay, including the presence of liver injury (LI), defined as aspartate aminotransferase (AST) >200 IU/L, were recorded. Results: On admission, 363 (34.7%) and 269 (25.7%) patients had abnormal AST and ALT values (i.e., >40 IU/L), respectively, while during hospitalization 53 (5%) patients fulfilled the criteria for LI. In multivariate logistic regression analysis, AST (odds ratio [OR] 1.023, 95% confidence interval [CI] 1.016-1.029; P<0.001), and ferritin (OR 1.01, 95%CI 1.001-1.02; P<0.001) were the baseline factors independently associated with the development of LI during hospital stay. One hundred twenty-three (11.7%) patients died during hospitalization. The independent variables associated with mortality were: age (hazard ratio [HR] 1.043, 95%CI 1.029-1.056; P<0.001), ferritin (HR 1.1, 95%CI 1.05-1.2; P<0.001), platelets (HR 0.996, 95%CI 0.994-0.999; P=0.003), and administration of remdesivir (HR 0.50, 95%CI 0.30-0.85; P=0.009). The patients with abnormal baseline AST (i.e., >40 IU/L), compared to those with normal AST values, had worse outcomes (log rank test: 8.8, P=0.003). Conclusions: Elevated aminotransferases are commonly seen in COVID-19 patients. They possibly reflect disease severity and may be associated with in-hospital mortality.
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We aimed to search for laboratory predictors of critical COVID-19 in consecutive adults admitted in an academic center between 16 September 2020−20 December 2021. Patients were uniformly treated with low-molecular-weight heparin, and dexamethasone plus remdesivir when SpO2 < 94%. Among consecutive unvaccinated patients without underlying medical conditions (n = 241, 49 year-old median, 71% males), 22 (9.1%) developed critical disease and 2 died (0.8%). White-blood-cell counts, neutrophils, neutrophil-to-lymphocyte ratio, CRP, fibrinogen, ferritin, LDH and γ-GT at admission were each univariably associated with critical disease. ROC-defined cutoffs revealed that CRP > 61.8 mg/L, fibrinogen > 616.5 mg/dL and LDH > 380.5 U/L were each associated with critical disease development, independently of age, sex and days from symptom-onset. A score combining higher-than-cutoff CRP (0/2), LDH (0/1) and fibrinogen (0/1) predicted critical disease (AUC: 0.873, 95% CI: 0.820−0.926). This score performed well in an unselected patient cohort (n = 1228, 100% unvaccinated) predominantly infected by the alpha variant (AUC: 0.718, 95% CI: 0.683−0.753), as well as in a mixed cohort (n = 527, 65% unvaccinated) predominantly infected by the delta variant (AUC: 0.708, 95% CI: 0.656−0.760). Therefore, we propose that a combination of standard biomarkers of acute inflammatory response, cell death and hypercoagulability reflects the severity of COVID-19 per se independently of comorbidities, age and sex, being of value for risk stratification in unselected patients.
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The purpose of this study was the molecular detection of Bartonella spp. in fleas and ticks parasitizing cats and dogs from 39 locations in Attica, Greece. One hundred and forty five ectoparasites (104 fleas and 41 ticks) from 92 cats and 53 dogs were investigated individually using PCRs targeting the 16S-23S ribosomal RNA intergenic spacer (ITS) and the citrate synthase (gltA) genetic loci. Bartonella spp. were detected in 14 out of 104 fleas (13.5%) and in none of the ticks examined. Consequent sequence analysis of the amplicons from the two loci identified 3 strains as Bartonella henselae, and 11 as Bartonella clarridgeiae. Οur study demonstrates the presence of B. henselae and B. clarridgeiae in Ctenocephalides felis fleas from cat and dog in Greece. We also report a novel ITS sequence for B. clarridgeiae. Considering that fleas could pose a risk for human bartonellosis from their infected hosts, further studies on the public health risk of Bartonella presence in animal ectoparasites are warranted.
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In the era of precision medicine, antibody-based therapeutics are rapidly enriched with emerging advances and new proof-of-concept formats. In this context, antibody-drug conjugates (ADCs) have evolved to merge the high selectivity and specificity of monoclonal antibodies (mAbs) with the cytotoxic potency of attached payloads. So far, ten ADCs have been approved by FDA for oncological indications and many others are currently being tested in clinical and preclinical level. This paper summarizes the essential components of ADCs, from their functional principles and structure up to their limitations and resistance mechanisms, focusing on all latest bioengineering breakthroughs such as bispecific mAbs, dual-drug platforms as well as novel linkers and conjugation chemistries. In continuation of our recent review on anticancer implication of ADC's technology, further insights regarding their potential usage outside of the oncological spectrum are also presented. Better understanding of immunoconjugates could maximize their efficacy and optimize their safety, extending their use in everyday clinical practice.