RESUMEN
Coronary artery disease (CAD), particularly three-vessel coronary disease (3VD), is the main cause of death in industrialized countries. Chronic kidney disease is an independent risk factor for CAD. The CHA2DS2-VASc score shows a good ability to predict CV events in high-risk population independently from atrial fibrillation. The aim of the present study was to evaluate the association between the R2CHA2DS2-VASc score and 3VD in a population of patients at high cardiovascular risk. Monocentric prospective study evaluated 1017 patients undergoing coronary angiography. The R2CHA2DS2-VASc score was obtained by adding 2 points to the CHA2DS2-VASc score in case of eGFR < 60 ml/min/1.73m2. Coronary lesions causing ≥ 50% reduction of a major epicardial vessel diameter were considered significant. Patients were grouped based on R2CHA2DS2-VASc tertiles and according to the severity of CAD: 3VD vs No-3VD. The 3VD group showed significantly higher R2CHA2DS2-VASc score than the No-3VD group (4.20 ± 2.18 vs 3.36 ± 2.06, p < 0.001). The risk of 3VD increased by 21% for every 1-point increase in the score (OR 1.21; 95% CI 1.13-1.28, p < 0.001). The prevalence of 3VD was higher among patients belonging to higher tertiles of R2CHA2DS2-VASc (17.2% vs 26.7% vs 33.6% for first, second, and third tertile respectively, p < 0.001) with a risk more than doubled for the third tertile compared to the first one (OR 2.45; 95% CI 1.71-3.49, p < 0.001). The R2CHA2DS2-VASc score is independently associated with 3VD in patients at high cardiovascular risk. The score could be considered a useful tool for clinicians to identify patients who are at high risk of 3VD.
RESUMEN
Emerging treatments for alcohol dependence reveal an intricate interplay of neurobiological, psychological, and circumstantial factors that contribute to Alcohol Use Disorder (AUD). The approved strategies balancing these factors involve extensive manipulations of neurotransmitter systems such as GABA, Glutamate, Dopamine, Serotonin, and Acetylcholine. Innovative developments are engaging mechanisms such as GABA reuptake inhibition and allosteric modulation. Closer scrutiny is placed on the role of Glutamate in chronic alcohol consumption, with treatments like NMDA receptor antagonists and antiglutamatergic medications showing significant promise. Complementing these neurobiological approaches is the progressive shift towards Personalized Medicine. This strategy emphasizes unique genetic, epigenetic and physiological factors, employing pharmacogenomic principles to optimize treatment response. Concurrently, psychological therapies have become an integral part of the treatment landscape, tackling the cognitive-behavioral dimension of addiction. In instances of AUD comorbidity with other psychiatric disorders, Personalized Medicine becomes pivotal, ensuring treatment and prognosis are closely defined by individual characteristics, as exemplified by Lesch Typology models. Given the high global prevalence and wide distribution of AUD, a persistent necessity exists for development and improvement of treatments. Current research efforts are steadily paving paths towards more sophisticated, effective typology-based treatments: a testament to the recognized imperative for enhanced treatment strategies. The potential encapsulated within the ongoing research suggests a promising future where the clinical relevance of current strategies is not just maintained but significantly improved to effectively counter alcohol dependence.
Asunto(s)
Alcoholismo , Humanos , Alcoholismo/terapia , Alcoholismo/epidemiología , Comorbilidad , Consumo de Bebidas Alcohólicas , Glutamatos , Ácido gamma-AminobutíricoRESUMEN
Objectives: We validated a screening protocol in which thoracic ultrasound (TUS) acts as a first-line complementary imaging technique in selecting patients which may deserve a second-line low-dose high resolution computed tomography (HRCT) scan among a population of asymptomatic high-risk subjects for interstitial lung abnormalities (ILA) and lung cancer. Due to heavy environmental pollution burden, the district Tamburi of Taranto has been chosen as "case study" for this purpose. Methods: From July 2018 to October 2020, 677 patients aged between 45 and 65 year and who had been living in the Tamburi district of Taranto for at least 10 years were included in the study. After demographic, clinical and risk factor exposition data were collected, each participant underwent a complete TUS examination. These subjects were then asked to know if they agreed to perform a second-level examination by low-dose HRCT scan. Results: On a total of 167 subjects (24.7%) who agreed to undergo a second-level HRCT, 85 patients (50.9%) actually showed pleuro-pulmonary abnormalities. Interstitial abnormalities were detected in a total of 36 patients on HRCT scan. In particular, 34 participants presented subpleural ILAs, that were classified in the fibrotic subtype in 7 cases. The remaining 2 patients showed non-subpleural interstitial abnormalities. Subpleural nodules were observed in 46 patients. TUS showed an overall diagnostic accuracy of 88.6% in detecting pleuro-pulmonary abnormalities in comparison with HRCT scan, with a sensitivity of 95.3%, a specificity of 81.7%, a positive predictive value of 84.4% and a negative predictive value of 94.4%. The matched evaluation of specific pulmonary abnormalities on HRTC scan (i.e., interstitial abnormalities or pulmonary nodules) with determinate sonographic findings revealed a reduction in both TUS sensibility and specificity. Focusing TUS evaluation on the assessment of interstitial abnormalities, a thickened pleural line showed a sensitivity of 63.9% and a specificity of 69.5%, hypoechoic striae showed a sensitivity of 38.9% and a specificity of 90.1% and subpleural nodules showed a sensitivity of 58.3% and a specificity of 77.1%. Regarding to the assessment of subpleural nodules, TUS showed a sensitivity of 60.9% and a specificity of 81.0%. However, the combined employment of TUS examination and HRCT scans allowed to identify 34 patients with early subpleural ILA and to detect three suspicious pulmonary nodules (of which two were intraparenchymal and one was a large subpleural mass), which revealed to be lung cancers on further investigations. Conclusion: A first-line TUS examination might aid the identification of subjects highly exposed to environmental pollution, who could benefit of a second-line low-dose HRCT scan to find early interstitial lung diseases as well as lung cancer. Protocol registration code: PLEURO-SCREENING-V1.0_15 Feb, 17.
RESUMEN
BACKGROUND AND AIMS: The CHA2DS2-VASc score estimates the risk of cardioembolism in patients with atrial fibrillation (AF). It also predicts vascular events and death in different clinical settings, even in the absence of AF. The R2CHA2DS2-VASc score, obtained by adding the glomerular filtration rate to CHA2DS2-VASc, shows a higher prediction ability for new events and all-cause mortality. The present study aims to assess whether the addition of albuminuria to R2CHA2DS2-VASc score further improves its discrimination ability in predicting all-cause mortality in a sample of high cardiovascular risk population. METHODS AND RESULTS: Prospective, monocentric, observational study, evaluating a subset of 737 subjects consecutively undergoing to coronary angiography at Coronary Unit of Scientific Institute "Casa Sollievo della Sofferenza" from June 2016 to December 2018. The presence of albuminuria was significantly associated with all-cause mortality (p < 0.0001). Any one-point increase of Alb-R2CHA2DS2-VASc score increased mortality of about 1.5-fold (adjusted HR 1.49; 95%CI: 1.37-1.63; p < 0.0001). Considering tertiles of Alb-R2CHA2DS2-VASc, the third tertile showed a 9.5-fold increased risk of mortality (HR 9.52; 95% CI: 5.15-17.60, p < 0.001). Comparing the two scores, the Alb-R2CHA2DS2-VASc score (C-statistic = 0.751; 95%CI: 0.69-0.81) outperformed the R2-CHA2DS2-VASc score (C-statistic = 0.736; 95%CI: 0.68-0.961) in predicting mortality (delta C-statistic = 0.015; 95%CI: 0.001-0.029). The better prediction ability of the Alb-R2CHA2DS2-VASc score was also proven by an IDI of 0.024 (p < 0.0001) and a relative IDI of 24.11% (p < 0.0001), with an NRI = 0.608 (p < 0.00001). CONCLUSIONS: The addition of albuminuria to R2CHA2DS2-VASc significantly and independently predicts the risk of all-cause mortality in a sample of high CV risk patients. Moreover, Alb-R2CHA2DS2-VASc outperforms R2CHA2DS2-VASc.
Asunto(s)
Fibrilación Atrial , Enfermedades Cardiovasculares , Accidente Cerebrovascular , Humanos , Factores de Riesgo , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/complicaciones , Estudios Prospectivos , Albuminuria/diagnóstico , Fibrilación Atrial/epidemiología , Factores de Riesgo de Enfermedad Cardiaca , Medición de Riesgo , Accidente Cerebrovascular/epidemiologíaRESUMEN
Background: Sepsis is a time-dependent disease: the early recognition of patients at risk for poor outcome is mandatory. Aim: To identify prognostic predictors of the risk of death or admission to intensive care units in a consecutive sample of septic patients, comparing different statistical models and machine learning algorithms. Methods: Retrospective study including 148 patients discharged from an Italian internal medicine unit with a diagnosis of sepsis/septic shock and microbiological identification. Results: Of the total, 37 (25.0%) patients reached the composite outcome. The sequential organ failure assessment (SOFA) score at admission (odds ratio (OR): 1.83; 95% confidence interval (CI): 1.41-2.39; p < 0.001), delta SOFA (OR: 1.64; 95% CI: 1.28-2.10; p < 0.001), and the alert, verbal, pain, unresponsive (AVPU) status (OR: 5.96; 95% CI: 2.13-16.67; p < 0.001) were identified through the multivariable logistic model as independent predictors of the composite outcome. The area under the receiver operating characteristic curve (AUC) was 0.894; 95% CI: 0.840-0.948. In addition, different statistical models and machine learning algorithms identified further predictive variables: delta quick-SOFA, delta-procalcitonin, mortality in emergency department sepsis, mean arterial pressure, and the Glasgow Coma Scale. The cross-validated multivariable logistic model with the least absolute shrinkage and selection operator (LASSO) penalty identified 5 predictors; and recursive partitioning and regression tree (RPART) identified 4 predictors with higher AUC (0.915 and 0.917, respectively); the random forest (RF) approach, including all evaluated variables, obtained the highest AUC (0.978). All models' results were well calibrated. Conclusions: Although structurally different, each model identified similar predictive covariates. The classical multivariable logistic regression model was the most parsimonious and calibrated one, while RPART was the easiest to interpret clinically. Finally, LASSO and RF were the costliest in terms of number of variables identified.
RESUMEN
Ultrasound (US) is acoustic energy that interacts with human tissues, thus, producing bioeffects that may be hazardous, especially in sensitive organs (i.e., brain, eye, heart, lung, and digestive tract) and embryos/fetuses. Two basic mechanisms of US interaction with biological systems have been identified: thermal and non-thermal. As a result, thermal and mechanical indexes have been developed to provide a means of assessing the potential for biological effects from exposure to diagnostic US. The main aims of this paper were to describe the models and assumptions used to estimate the "safety" of acoustic outputs and indices and to summarize the current state of knowledge about US-induced effects on living systems deriving from in vitro models and in vivo experiments on animals. This review work has made it possible to highlight the limits associated with the use of the estimated safety values of thermal and mechanical indices relating above all to the use of new US technologies, such as contrast-enhanced ultrasound (CEUS) and acoustic radiation force impulse (ARFI) shear wave elastography (SWE). US for diagnostic and research purposes has been officially declared safe, and no harmful biological effects in humans have yet been demonstrated with new imaging modalities; however, physicians should be adequately informed on the potential risks of biological effects. US exposure, according to the ALARA (As Low As Reasonably Achievable) principle, should be as low as reasonably possible.
RESUMEN
Abdominal pain represents a frequent symptom for referral to emergency departments and/or internal medicine outpatient setting. Similarly, fever, fatigue and weight loss are non-specific manifestations of disease. The present case describes the diagnostic process in a patient with abdominal pain and a palpable abdominal mass. Abdominal ultrasonography confirmed the presence of a mass in the mesogastrium. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) scans oriented toward calcific lymphadenopathies with increased metabolism in the positron emission tomography-computed tomography (PET-CT) scan. Laboratory examinations were inconclusive, although serology for Brucella and the Quantiferon test were positive. After multidisciplinary discussion, the patient underwent surgical excision of the abdominal mass. Histological examination excluded malignancies and oriented toward brucellosis in a patient with latent tuberculosis. The patient was treated with rifampin 600 mg qd and doxycycline 100 mg bid for 6 weeks with resolution of the symptoms. In addition, rifampin was continued for a total of 6 months in order to treat latent tuberculosis. This case underlines the need for a multidisciplinary approach in the diagnostic approach to abdominal lymphadenopathies.
Asunto(s)
Brucelosis , Tuberculosis Latente , Linfadenopatía , Linfoma , Tuberculosis , Humanos , Rifampin , Tomografía Computarizada por Tomografía de Emisión de Positrones , Brucelosis/diagnóstico , Dolor AbdominalRESUMEN
Background. Limited studies and observations conducted on a too small number of patients prevent determining the actual clinical utility of pulmonary contrast-enhanced ultrasound (CEUS). The aim of the present study was to examine the efficacy of contrast enhancement (CE) arrival time (AT) and other dynamic CEUS findings for differentiating between malignant and benign peripheral lung lesions. Methods. 317 inpatients and outpatients (215 men, 102 women; mean age: 52 years) with peripheral pulmonary lesions were included in the study and underwent pulmonary CEUS. Patients were examined in a sitting position after receiving an intravenous injection of 4.8 mL of sulfur hexafluoride microbubbles stabilized by a phospholipid shell as ultrasound contrast agent (SonoVue-Bracco; Milan, Italy). Each lesion was observed for at least 5 min in real-time and the following temporal characteristics of enhancement were detected: the arrival time (AT) of microbubbles in the target lesion; the enhancement pattern; the wash-out time (WOT) of microbubbles. Results were then compared in light of the definitive diagnosis of community acquired pneumonia (CAP) or malignancies, which was not known at the time of CEUS examination. All malignant cases were diagnosed by histological results, while pneumonia was diagnosed on the basis of clinical and radiological follow-up, laboratory findings and, in some cases, histology. Results. CE AT has not been shown to differ between benign and malignant peripheral pulmonary lesions. The overall diagnostic accuracy and sensibility of a CE AT cut-off value < 10 s in discriminating benign lesions were low (diagnostic accuracy: 47.6%; sensibility: 5.3%). Poor results were also obtained in the sub-analysis of small (mean diameter < 3 cm) and large (mean diameter > 3 cm) lesions. No differences were recorded in the type of CE pattern showed between benign and malignant peripheral pulmonary lesions. In benign lesions we observed a higher frequency of delayed CE wash-out time (WOT) > 300 s. Anyhow, a CE WOT cut-off value > 300 s showed low diagnostic accuracy (53.6%) and sensibility (16.5%) in discriminating between pneumonias and malignancies. Similar results were also obtained in the sub-analysis by lesion size. Squamous cell carcinomas showed a more delayed CE AT compared to other histopathology subtypes. However, such a difference was statistically significant with undifferentiated lung carcinomas. Conclusions. Due to an overlap of CEUS timings and patterns, dynamic CEUS parameters cannot effectively differentiate between benign and malignant peripheral pulmonary lesions. Chest CT remains the gold standard for lesion characterization and the eventual identification of other pneumonic non-subpleural localizations. Furthermore, in the case of malignancy, a chest CT is always needed for staging purposes.
RESUMEN
Acute alcohol intoxication (AAI) is a harmful clinical condition, potentially life-threatening, secondary to the intake of large amounts of alcohol. Clinical manifestations of AAI are characterized by behavioural and neurological symptoms, even if its effects involve several organs and apparatus. Moreover, severe alcohol intoxication can produce a global neurological impairment leading to autonomic dysfunction, respiratory depression, coma and cardiac arrest. The evaluation of blood alcohol concentrations (BAC) is useful to confirm the suspicion of intoxication, both for clinical and legal reasons. Most of patients with AAI are referred to Emergency Departments due to behavioural, social, traumatic or clinical complications. Patient's stabilization is the first step in the management of AAI, in order to support vital functions and to prevent complications. Metadoxine represents a useful drug to increase ethanol metabolism and elimination. Given that AAI could represent a sentinel event of chronic alcohol abuse, patients presenting with acute intoxication should be screened for the presence of an underlying alcohol use disorder and referred to and an alcohol addiction unit to start a multidisciplinary treatment to achieve long term alcohol abstinence. The present review will focus on clinical features, diagnostic criteria and treatment strategies of AAI.
Asunto(s)
Intoxicación Alcohólica , Alcoholismo , Humanos , Intoxicación Alcohólica/diagnóstico , Intoxicación Alcohólica/terapia , Alcoholismo/complicaciones , Alcoholismo/diagnóstico , Alcoholismo/terapia , Etanol , Nivel de Alcohol en Sangre , Consumo de Bebidas AlcohólicasRESUMEN
BACKGROUND: The CHA2 DS2 -VASc score, widely used to estimate cardioembolic risk in patients with atrial fibrillation (AF), appears to be useful also in predicting vascular adverse events and death in different sets of patients without AF. The R2 CHA2 DS2 -VASc score, which includes renal impairment, allows a better prediction of death and thromboembolism in patients without AF. The aims of our study were to assess, in a large sample of patients at high cardiovascular (CV) risk, (i) the correlation between CHA2 DS2 -VASc and R2 CHA2 DS2 -VASc with all-cause mortality, and (ii) to compare the performances of CHA2 DS2 -VASc and R2 CHA2 DS2 -VASc in predicting all-cause mortality. METHODS: In this single-centre prospective observational study, conducted at the Research Hospital 'Casa Sollievo della Sofferenza' between June 2016 and December 2018, 1017 CV patients at high risk of undergoing coronary angiography were enrolled. RESULTS: CHA2DS2-VASc and R2 CHA2 DS2 -VASc scores significantly associated with all-cause mortality. For each one-point increase in CHA2 DS2 -VASc or R2 CHA2 DS2 -VASc scores, mortality increased by almost 1.5-fold. The R2 CHA2 DS2 -VASc score (C-statistic = 0.71; 95% CI = 0.65-76) outperformed the CHA2 DS2 -VASc score (C-statistic = 0.66; 95% CI = 0.61-0.71) in predicting 4-year mortality (delta C-statistic = 0.05; 95% CI = 0.02-0.07). The better predictive ability of the R-CHA2 DS2 -VASc score was also demonstrated by an IDI = 0.027 (95% CI = 0.021-0.034, p < .00001) and a relative IDI = 62.8% (95% CI = 47.9%-81.3%, p < .00001). The R2 CHA2 DS2 -VASc score correctly reclassified the patients with a NRI = 0.715 (95% = 0.544-0.940, p < .00001). CONCLUSIONS: The CHA2DS2-VASc and R2 CHA2 DS2 -VASc scores are useful predictors of all-cause mortality in subjects at high CV risk, with the R2 CHA2 DS2 -VASc score being the best performer.
Asunto(s)
Fibrilación Atrial , Enfermedades Cardiovasculares , Accidente Cerebrovascular , Fibrilación Atrial/complicaciones , Enfermedades Cardiovasculares/epidemiología , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/etiologíaRESUMEN
BACKGROUND: Sodium oxybate (SMO) has been shown to be effective in the maintenance of abstinence (MoA) in alcohol-dependent patients in a series of small randomized controlled trials (RCTs). These results needed to be confirmed by a large trial investigating the treatment effect and its sustainability after medication discontinuation. AIMS: To confirm the SMO effect on (sustained) MoA in detoxified alcohol-dependent patients. METHODS: Large double-blind, randomized, placebo-controlled trial in detoxified adult alcohol-dependent outpatients (80% men) from 11 sites in four European countries. Patients were randomized to 6 months SMO (3.3-3.9 g/day) or placebo followed by a 6-month medication-free period. Primary outcome was the cumulative abstinence duration (CAD) during the 6-month treatment period defined as the number of days with no alcohol use. Secondary outcomes included CAD during the 12-month study period. RESULTS: Of the 314 alcohol-dependent patients randomized, 154 received SMO and 160 received placebo. Based on the pre-specified fixed-effect two-way analysis of variance including the treatment-by-site interaction, SMO showed efficacy in CAD during the 6-month treatment period: mean difference +43.1 days, 95% confidence interval (17.6-68.5; p = 0.001). Since significant heterogeneity of effect across sites and unequal sample sizes among sites (n = 3-66) were identified, a site-level random meta-analysis was performed with results supporting the pre-specified analysis: mean difference +32.4 days, p = 0.014. The SMO effect was sustained during the medication-free follow-up period. SMO was well-tolerated. CONCLUSIONS: Results of this large RCT in alcohol-dependent patients demonstrated a significant and clinically relevant sustained effect of SMO on CAD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04648423.
Asunto(s)
Alcoholismo , Oxibato de Sodio , Adulto , Consumo de Bebidas Alcohólicas , Alcoholismo/tratamiento farmacológico , Método Doble Ciego , Etanol , Femenino , Humanos , Masculino , Oxibato de Sodio/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: The development of alcoholic cardiomyopathy (ACM) is related to chronic excessive alcohol use. However, features of early-stage ACM are still unclear. We assessed echocardiographic characteristics of patients with alcohol dependence (DSM-IV criteria) during a six-month treatment period. METHODS: Active drinking patients, heavy alcohol users, without heart disease, referred to our Alcohol Addiction Unit were enrolled in the study. After signing informed consent, patients started outpatient treatment program. Echocardiography was performed at enrollment, then three and six months afterwards, by cardiologists blinded to drinking status. RESULTS: Forty-three patients (36 males, 7 females) were enrolled. At six months, 20 patients (46.5%) reduced alcohol consumption below heavy drinking levels. Although within normal range, baseline mean IVS thickness and mean LVDD were significantly higher (p < 0.001) and mean EF significantly reduced (p = 0.009), as compared to age-matched mean references. Mean E/A ratio, DcT and LA diameter were significantly different (p < 0.001) from mean references, but within normal range. Baseline mean E/e' ratio was significantly higher than the mean reference (p < 0.001) and out of the normal range. A significant correlation between the number of drinks per drinking days in the 7 days before baseline assessment and E/e' ratio was observed (p = 0.028). After six months, a trend-level reduction of mean E/e' ratio (p = 0.051) was found in the whole sample; this reduction was statistically significant (p = 0.041) among patients reducing drinking, compared to baseline. CONCLUSIONS: Altered E/e' ratio may characterize early-ACM before the occurrence of relevant echocardiographic alterations. The reduction of alcohol consumption could restore this alteration after six months.
Asunto(s)
Cardiomiopatía Alcohólica , Disfunción Ventricular Izquierda , Biomarcadores , Cardiomiopatía Alcohólica/diagnóstico por imagen , Ecocardiografía , Femenino , Humanos , Estudios Longitudinales , Masculino , Disfunción Ventricular Izquierda/epidemiología , Función Ventricular IzquierdaRESUMEN
Alcohol use disorder (AUD) is one of the main causes of global death and disability. The liver represents the main target of alcohol damage, and alcohol-associated liver disease (ALD) represents the first cause of liver cirrhosis in Western countries. Alcohol abstinence is the main goal of treatment in AUD patients with ALD, as treatments for ALD are less effective when drinking continues. Moreover, the persistence of alcohol consumption is associated with higher mortality, increased need for liver transplantation, and graft loss. The most effective treatment for AUD is the combination of psychosocial interventions, pharmacological therapy, and medical management. However, the effectiveness of these treatments in patients with ALD is doubtful even because AUD patients with ALD are usually excluded from pharmacological trials due to concerns on liver safety. This narrative review will discuss the treatment options for AUD-ALD patients focusing on controversies in pharmacological therapy.
Asunto(s)
Alcoholismo , Hepatopatías Alcohólicas , Trasplante de Hígado , Abstinencia de Alcohol , Consumo de Bebidas Alcohólicas/efectos adversos , Alcoholismo/complicaciones , Alcoholismo/tratamiento farmacológico , Humanos , Hepatopatías Alcohólicas/complicaciones , Hepatopatías Alcohólicas/tratamiento farmacológico , Trasplante de Hígado/efectos adversosRESUMEN
BACKGROUND: A significant proportion of patients with coronavirus disease 2019 (COVID-19) suffer from delirium during hospitalization. This single-center observational study investigates the occurrence of delirium, the associated risk factors and its impact on in-hospital mortality in an Italian cohort of COVID 19 inpatients. METHODS: Data were collected in the COVID units of a general medical hospital in the South of Italy. Socio-demographic, clinical and pharmacological features were collected. Diagnosis of delirium was based on a two-step approach according to 4AT criteria and DSM5 criteria. Outcomes were: dates of hospital discharge, Intensive Care Unit (ICU) admission, or death, whichever came first. Univariable and multivariable proportional hazards Cox regression models were estimated, and risks were reported as hazard ratios (HR) along with their 95% confidence intervals (95% CI). RESULTS: A total of 47/214 patients (22%) were diagnosed with delirium (21 hypoactive, 15 hyperactive, and 11 mixed). In the multivariable model, four independent variables were independently associated with the presence of delirium: dementia, followed by age at admission, C-reactive protein (CRP), and Glasgow Coma Scale. In turn, delirium was the strongest independent predictor of death/admission to ICU (composite outcome), followed by Charlson Index (not including dementia), CRP, and neutrophil-to-lymphocyte ratio. The probability of reaching the composite outcome was higher for patients with the hypoactive subtype than for those with the hyperactive subtype. CONCLUSIONS: Delirium was the strongest predictor of poor outcome in COVID-19 patients, especially in the hypoactive subtype. Several clinical features and inflammatory markers were associated with the increased risk of its occurrence. The early recognition of these factors may help clinicians to select patients who would benefit from both non-pharmacological and pharmacological interventions in order to prevent delirium, and in turn, reduce the risk of admission to ICU or death.
RESUMEN
Remdesivir is a broad-spectrum antiviral agent able to inhibit the RNA polymerase of SARS-CoV-2. At present, studies focusing on the effect of remdesivir on viral load (VL) are few and with contrasting results. Aim of the present study was to evaluate the effect of remdesivir on SARS-CoV-2 VL from nasopharyngeal swabs (cycle threshold criterion) in a sample of patients treated with the drug, compared with patients who did not receive the antiviral treatment. This retrospective analysis evaluated patients with (1) real-time polymerase chain reaction (RT-PCR) confirmed COVID-19 diagnosis and (2) availability of at least two positive nasopharyngeal swabs analysed with the same analytic platform (ORF target gene, Ingenius ELITe, ELITechGroup, Puteaux, France). Upper respiratory specimens from nasopharyngeal swabs were collected at admission (T0) and 7-14 days after treatment, upon clinical decision. A total of 27 patients treated with remdesivir (Group A) met the inclusion criteria and were compared with 18 patients (Group B) treated with standard care, matched for baseline clinical characteristics. At baseline, both remdesivir-treated and nontreated patients showed comparable VLs (21.73 ± 6.81 vs. 19.27 ± 5.24, p = 0.348). At the second swab, remdesivir-treated patients showed a steeper VL reduction with respect to controls (34.28 ± 7.73 vs. 27.22 ± 3.92; p < 0.001). Longitudinal linear model estimated a mean decrease in cycle threshold equal to 0.61 (SE: 0.09) per day in remdesivir-treated versus 0.33 (SE: 0.10) per day in remdesivir nontreated patients (p for heterogeneity = 0.045). The present study shows that the administration of remdesivir in hospitalized COVID-19 patients significantly reduces the VL on nasopharyngeal swabs.
Asunto(s)
Tratamiento Farmacológico de COVID-19 , COVID-19 , SARS-CoV-2 , Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , COVID-19/diagnóstico , Prueba de COVID-19 , Estudios de Casos y Controles , Humanos , Nasofaringe , Estudios Retrospectivos , Carga ViralRESUMEN
BACKGROUND AND AIM: Three vessels disease (3VD) has been associated with worse prognosis and higher mortality. Chronic kidney disease (CKD) is an independent risk factor for premature death, mostly due to coronary artery disease (CAD). We aim to examine the prognostic impact of 3VD on all-cause mortality in a cohort of high cardiovascular risk subjects undergoing coronary angiography (CA) and to explore whether low eGFR (<60 ml/min/1.73 m2) modulates the risk of all-cause mortality associated to 3VD. METHODS AND RESULTS: One-thousand-seventeen subjects (759 M, mean age 68.4 ± 11 years) consecutive subjects undergoing CA from 2016 to 2018 were evaluated. Subjects were classified according to the severity of CAD as follows: group "three vessels disease" (3VD), and "no three vessels disease" (No 3VD). Serum creatinine was measured to estimate glomerular filtration rate (eGFR). The whole population was divided into 4 groups (A, B, C, D), according to the presence/absence of low eGFR and/or 3VD. One-hundred-fourteen deaths occurred (median follow-up:44 months). The risk of death in subjects with 3VD was almost 2-time higher than subject without 3VD (adjusted HR = 1.61; 95% CI 1.094-2.373, p = 0.0157). Among 4 subgroups, subjects with low eGFR and 3VD (Group D) had the highest risk of death (adjusted HR = 3.881; 95% CI 2.256-6.676, p < 0.0001). CONCLUSIONS: Low eGFR significantly amplifies the risk of all-cause mortality associated to 3VD. Our results strengthen the role of kidney disease as a risk multiplier for cardiovascular and all-cause mortality and highlight the need to prevent its onset and progression.