RESUMEN
COVID-19 disease has been a challenge for health systems worldwide due to its high transmissibility, morbidity, and mortality. Severe COVID-19 is associated with an imbalance in the immune response, resulting in a cytokine storm and a hyperinflammation state. While hematological parameters correlate with prognosis in COVID patients, their predictive value has not been evaluated specifically among those severely ill. Therefore, we aim to evaluate the role of hematological and immune response biomarkers as a prognostic factor in critically ill patients with COVID-19 admitted to the intensive care unit. From May 2020 to July 2021, a retrospective cohort study was conducted in a reference hospital in Manaus, which belongs to the Brazilian public health system. This study was carried out as single-center research. Clinical and laboratory parameters were analyzed to evaluate the association with mortality. We also evaluated the role of neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein-to-lymphocyte ratio (CLR). We gathered information from medical records, as well as from prescriptions and forms authorizing the use of antimicrobial medications. During the study period, 177 patients were included, with a mean age of 62.58 ± 14.39 years. The overall mortality rate was 61.6%. Age, mechanical ventilation (MV) requirement, leukocytosis, neutrophilia, high c-reactive protein level, NLR, and CLR showed a statistically significant association with mortality in the univariate analysis. In the multivariate logistic regression analysis, only MV (OR 35.687, 95% CI: 11.084-114.898, p< 0.001) and NLR (OR 1.026, 95% CI: 1.003-1.050, p = 0.028) remained statistically associated with the outcome of death (AUC = 0.8096). While the need for mechanical ventilation is a parameter observed throughout the hospital stay, the initial NLR can be a primary risk stratification tool to establish priorities and timely clinical intervention in patients with severe COVID-19 admitted to the ICU.
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Proteína C-Reactiva , COVID-19 , Humanos , Persona de Mediana Edad , Anciano , Pronóstico , Estudios Retrospectivos , Biomarcadores , LeucocitosisRESUMEN
COVID-19 is a contagious infection caused by the SARS-CoV-2 virus, responsible for more than 5 million deaths worldwide, and has been a significant challenge for healthcare systems worldwide. Characterized by multiple manifestations, the most common symptoms are fever, cough, anosmia, ageusia, and myalgia. However, several organs can be affected in more severe cases, causing encephalitis, myocarditis, respiratory distress, hypercoagulable state, pulmonary embolism, and stroke. Despite efforts to identify appropriate clinical protocols for its management, there are still no fully effective therapies to prevent patient death. The objective of this study was to describe the demographic, clinical, and pharmacotherapeutic management characteristics employed in patients hospitalized for diagnosis of COVID-19, in addition to identifying predictive factors for mortality. This is a single-center, retrospective cohort study carried out in a reference hospital belonging to the Brazilian public health system, in Manaus, from March 2020 to July 2021. Data were obtained from analyzing medical records, physical and electronic forms, medical prescriptions, and antimicrobial use authorization forms. During the study period, 530 patients were included, 51.70% male, with a mean age of 58.74 ± 15.91 years. The overall mortality rate was 23.58%. The variables age, number of comorbidities, admission to the ICU, length of stay, oxygen saturation, serum aspartate transaminase, and use of mechanical ventilation showed a positive correlation with the mortality rate. Regarding pharmacological management, 88.49% of patients used corticosteroids, 86.79% used antimicrobials, 94.15% used anticoagulant therapy, and 3.77% used immunotherapy. Interestingly, two specific classes of antibiotics showed a positive correlation with the mortality rate: penicillins and glycopeptides. After multivariate logistic regression analysis, age, number of comorbidities, need for mechanical ventilation, length of hospital stay, and penicillin or glycopeptide antibiotics use were associated with mortality (AUC = 0.958).
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COVID-19 , Humanos , Masculino , Adulto , Persona de Mediana Edad , Anciano , Femenino , Estudios Retrospectivos , SARS-CoV-2 , Respiración Artificial , Hospitales , Antibacterianos/uso terapéutico , Mortalidad HospitalariaRESUMEN
Therapeutic hypothermia has been shown to improve neurological outcomes in patients who remain comatose following resuscitation from cardiac arrest. While there are numerous reports of patients who have had a successful course after induction of therapeutic hypothermia, such therapeutic intervention has not been described in patients with congenital long QT syndrome (LQTS). We report outcomes in two patients with LQTS who had therapeutic hypothermia following a ventricular fibrillation arrest. Careful and routine monitoring of the QT interval in this patient population is necessary due to the potential for worsening electrical instability during induced hypothermia.
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Hipotermia Inducida , Síndrome de QT Prolongado/terapia , Adulto , Niño , Electrocardiografía , Femenino , Humanos , Síndrome de QT Prolongado/congénito , Masculino , Paro Cardíaco Extrahospitalario/etiología , Paro Cardíaco Extrahospitalario/terapia , Trastornos Puerperales/terapia , Fibrilación Ventricular/complicacionesRESUMEN
INTRODUCTION: Therapeutic hypothermia has been shown to provide neuroprotection and improved survival in patients suffering a cardiac arrest. We report outcomes of consecutive patients receiving therapeutic hypothermia for cardiac arrest and describe predictors of short and long-term survival. METHODS: Eighty patients receiving therapeutic hypothermia between January 2005 and December 2008 were identified and categorized as those who survived and died. Outcomes and predictors of survival were determined. RESULTS: Forty-five patients (56%) survived to hospital discharge and were alive at 30 days and among survivors 41 (91%) were alive 1 year after discharge. Survivors were younger, were more likely to present with VF, required less epinephrine during resuscitation, were more likely to have preserved renal function, and were less likely to be taking beta-blockers and ACE inhibitors. Predictors of survival included VF on presentation (OR 14.9, CI 2.7-83.2, p=0.002), pre-cardiac arrest aspirin use (OR 9.7, CI 1.6-61.1, p=0.02), return of spontaneous circulation <20 min (OR 9.4, CI 2.2-41.1, p=0.003), absence of coronary artery disease (OR 5.3, CI 1.1-24.7, p=0.002) and preserved renal function. CONCLUSION: Therapeutic hypothermia is useful in the treatment of patients suffering a cardiac arrest. Several clinical factors may aid in predicting patients who are likely to survive after a cardiac arrest.
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Paro Cardíaco/mortalidad , Paro Cardíaco/terapia , Hipotermia Inducida , Factores de Edad , Circulación Sanguínea , Femenino , Paro Cardíaco/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Resultado del Tratamiento , Fibrilación Ventricular/complicacionesRESUMEN
The Medtronic Sprint Fidelis leads (models 6930, 6931, 6948, 6949) are 6.6-F bipolar high-voltage implantable cardioverter-defibrillator electrodes that were first introduced in September 2004. In October 2007, Fidelis leads were removed from the market. We sought to determine the time-dependent hazard of the Fidelis failure rate to date. A retrospective chart review was conducted in all patients who underwent implantation of a Sprint Fidelis lead (426 leads) at our center. We primarily implanted models 6931 and 6949. With 1,056 years of combined follow-up (average 2.3 +/- 1), 38 of 426 (8.92%) Sprint Fidelis leads failed (3.6%/year). The hazard of fracture increased exponentially over time by a power of 2.13 (95% confidence interval [CI] 1.98 to 2.27, p <0.001) and the 3-year survival was 90.8% (95% CI 87.4 to 94.3). If a Fidelis lead was functioning normally at 1 year, the chance it would survive another year was 97.4% (95% CI 95.7 to 99.1); if functioning at 2 years, the chance of surviving another year was 94.7% (95% CI 91.8 to 97.7); and if functioning at 3 years, the chance of surviving 1 more year was 86.7% (95% CI 78.8 to 95.5). Other commonly used implantable cardioverter-defibrillator leads showed no evidence of increased failure rates. In conclusion, to date, the hazard of Fidelis lead fracture is increasing exponentially with time and, based on our data, occurring at a higher rate than the latest manufacturer's performance update. Further accumulative data are needed because it remains unknown if the fracture rate will level off or continue to increase.
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Arritmias Cardíacas/terapia , Desfibriladores Implantables , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Arritmias Cardíacas/mortalidad , Falla de Equipo , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Factores de Tiempo , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: In Enterobacteriaceae, ß-lactam antibiotic resistance involves murein recycling intermediates. Murein recycling is a complex process with discrete steps taking place in the periplasm and the cytoplasm. The AmpG permease is critical to this process as it transports N-acetylglucosamine anhydrous N-acetylmuramyl peptides across the inner membrane. In Pseudomonadaceae, this intrinsic mechanism remains to be elucidated. Since the mechanism involves two cellular compartments, the characterization of transporters is crucial to establish the link. RESULTS: Pseudomonas aeruginosa PAO1 has two ampG paralogs, PA4218 (ampP) and PA4393 (ampG). Topology analysis using ß-galactosidase and alkaline phosphatase fusions indicates ampP and ampG encode proteins which possess 10 and 14 transmembrane helices, respectively, that could potentially transport substrates. Both ampP and ampG are required for maximum expression of ß-lactamase, but complementation and kinetic experiments suggest they act independently to play different roles. Mutation of ampG affects resistance to a subset of ß-lactam antibiotics. Low-levels of ß-lactamase induction occur independently of either ampP or ampG. Both ampG and ampP are the second members of two independent two-gene operons. Analysis of the ampG and ampP operon expression using ß-galactosidase transcriptional fusions showed that in PAO1, ampG operon expression is ß-lactam and ampR-independent, while ampP operon expression is ß-lactam and ampR-dependent. ß-lactam-dependent expression of the ampP operon and independent expression of the ampG operon is also dependent upon ampP. CONCLUSIONS: In P. aeruginosa, ß-lactamase induction occurs in at least three ways, induction at low ß-lactam concentrations by an as yet uncharacterized pathway, at intermediate concentrations by an ampP and ampG dependent pathway, and at high concentrations where although both ampP and ampG play a role, ampG may be of greater importance. Both ampP and ampG are required for maximum induction. Similar to ampC, ampP expression is inducible in an ampR-dependent manner. Importantly, ampP expression is autoregulated and ampP also regulates expression of ampG. Both AmpG and AmpP have topologies consistent with functions in transport. Together, these data suggest that the mechanism of ß-lactam resistance of P. aeruginosa is distinct from well characterized systems in Enterobacteriaceae and involves a highly complicated interaction between these putative permeases and known Amp proteins.
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Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica , Proteínas de Transporte de Membrana/metabolismo , Pseudomonas aeruginosa/enzimología , beta-Lactamasas/biosíntesis , Activación Transcripcional , Resistencia betalactámica , beta-Lactamas/metabolismoRESUMEN
A major limitation of adenovirus type 5-mediated cancer gene therapy is the inefficient infection of many cancer cells. Previously, we showed that treatment with low doses of the histone deacetylase inhibitor FK228 (FR901228, depsipeptide) increased coxsackie adenovirus receptor (CAR) levels, histone H3 acetylation, and adenovirus infection efficiencies as measured by viral transgene expression in cancer cell lines but not in cultured normal cells. To evaluate FK228 in vivo, the effects of FK228 therapy in athymic mice bearing LOX IMVI or UACC-62 human melanoma xenografts were examined. Groups of mice were treated with FK228 using several dosing schedules and the differences between treated and control animals were determined. In mice with LOX IMVI xenografts (n = 6), maximum CAR induction was observed 24 h following a single FK228 dose of 3.6 mg/kg with a 13.6 +/- 4.3-fold (mean +/- SD) increase in human CAR mRNA as determined by semiquantitative reverse transcription-PCR analysis. By comparison, mouse CAR levels in liver, kidney, and lung from the same animals showed little to no change. Maximum CAR protein induction of 9.2 +/- 4.8-fold was achieved with these treatment conditions and was associated with increased histone H3 acetylation. Adenovirus carrying a green fluorescent protein (GFP) transgene (2 x 10(9) viral particles) was injected into the xenografts and GFP mRNA levels were determined. A 7.4 +/- 5.2-fold increase in GFP mRNA was found 24 h following adenovirus injection into optimally FK228-treated mice (n = 10). A 4-fold increase in GFP protein-positive cells was found following FK228 treatment. These studies suggest that FK228 treatment prior to adenovirus infection could increase the efficiency of adenovirus gene therapy in xenograft model systems.