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1.
J Intensive Care Med ; : 8850666241265671, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39043370

RESUMEN

BACKGROUND: Propofol, a commonly used agent for short- and long-term sedation, is associated with acute pancreatitis. The main indirect mechanism of propofol-associated acute pancreatitis is by inducing hypertriglyceridemia. Patients with severe coronavirus disease 2019 (COVID-19) pneumonia often require prolonged mechanical ventilation and sedation. We examined the incidence rate of acute pancreatitis among critically ill adults with COVID-19 pneumonia on mechanical ventilation receiving propofol. In addition, we attempted to determine cutoff levels of serum triglycerides and doses of propofol that are predictive of propofol-associated acute pancreatitis. METHODS: This was a multicenter retrospective cohort study using a large dataset of hospitalized patients with COVID-19. The collected data included the number of days on propofol, cumulative doses of propofol, peak levels of serum triglycerides, serum lipase levels, and abdominal imaging findings. We used receiver-operating characteristic analysis in conjunction with Youden's index to identify the optimal thresholds for propofol administration parameters and levels of triglycerides that would provide maximal sensitivity and specificity for predicting acute pancreatitis. RESULTS: Out of 499 critically ill patients with COVID-19 pneumonia, 154 met the inclusion criteria. Six (4%) patients had suspected acute pancreatitis based on elevated serum lipase levels. Cutoff values greater than 688 mg/dL for peak level of triglycerides, 4.5 days on propofol, 3007 mg/day for average daily propofol dose, and 24 113 mg for cumulative propofol dose were associated with high risk of suspected acute pancreatitis. The negative predictive values for suspected acute pancreatitis using these cutoffs ranged from 98% to 100%. CONCLUSIONS: Propofol use in critically ill COVID-19 patients is associated with a low incidence rate of acute pancreatitis. We identified cutoff values for serum triglycerides and cumulative propofol dose that are linked to higher risk of propofol-associated pancreatitis. More research is needed to examine the true incidence of propofol-associated pancreatitis and help develop optimal cutoff values for certain parameters to help guide safe propofol administration.

2.
J Intensive Care Med ; 39(8): 768-777, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38343031

RESUMEN

Purpose: This study examines whether excessive adipose tissue, as measured by the body mass index (BMI), is associated with higher systemic markers of inflammation and higher risk of severe acute organ failure among patients with coronavirus disease 2019 (COVID-19). Methods: This was a multicenter retrospective cohort study of 1370 hospitalized adults (18 years or older) with COVID-19 during the first wave of the pandemic. Patient-level variables were extracted from the electronic medical record. The primary predictor variable was the BMI at time of hospital admission, in accordance with the World Health Organization classification. Multivariable logistic regression analyses examined the association of BMI with the composite of acute respiratory distress syndrome (ARDS), as defined by the use of high-flow nasal canula, non-invasive ventilation, or mechanical ventilation, severe acute kidney injury (AKI), as defined by acute dialysis requirement, or in-hospital death. Results: After adjustment for important cofounders, the BMI stratum of > 40 kg/m2 (compared to the BMI < 25 kg/m2 reference group) was associated with higher odds for the composite of ARDS, severe AKI, or in-hospital death (adjusted odds ratio [ORadj] 1.69; 95% confidence interval [CI]1.03, 2.78). As a continuous variable, BMI (per 5-kg/m2 increase) remained independently associated with the composite outcome (ORadj 1.13; 95% CI 1.03, 1.23); patients in higher BMI categories exhibited significantly higher peak levels of C-reactive protein (CRP), a systemic marker of inflammation (P = .01). In a sub-cohort of 889 patients, the association of BMI with the composite outcome was no longer significant after adjustment for the peak level of CRP. Conclusions: Among hospitalized patients with COVID-19, a higher BMI is associated with higher risk of severe organ failure or in-hospital death, which dissipates after adjustment for CRP level. This supports the hypothesis that inflammation is a downstream mediator of adipose tissue on acute organ dysfunction.


Asunto(s)
Índice de Masa Corporal , COVID-19 , Mortalidad Hospitalaria , Insuficiencia Multiorgánica , SARS-CoV-2 , Humanos , COVID-19/complicaciones , COVID-19/mortalidad , COVID-19/terapia , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Insuficiencia Multiorgánica/mortalidad , Insuficiencia Multiorgánica/etiología , Anciano , Hospitalización/estadística & datos numéricos , Síndrome de Dificultad Respiratoria/mortalidad , Síndrome de Dificultad Respiratoria/terapia , Síndrome de Dificultad Respiratoria/etiología , Lesión Renal Aguda/terapia , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/etiología , Adulto , Factores de Riesgo , Obesidad/complicaciones , Proteína C-Reactiva/análisis
3.
Nephron ; 146(6): 584-592, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35675790

RESUMEN

BACKGROUND: Acute kidney injury (AKI) is a well-recognized complication of coronavirus disease 2019 (COVID-19). The short and long-term outcomes of patients who develop AKI have not been well characterized. METHODS: In this multicenter retrospective cohort study, we describe the clinical characteristics and outcomes of critically ill adults with severe COVID-19 and AKI. Patient-level variables were extracted from the electronic medical record. Using nadir-to-peak serum creatinine, AKI was defined using the KDIGO definition. Multivariable logistic regression analyses examined factors associated with development of moderate-to-severe (stage 2-3) AKI, severe (stage-3) AKI, and the composite of renal replacement therapy (RRT) or in-hospital death. RESULTS: Among 459 critically ill adults with COVID-19, 371 (80.1%) developed AKI, with 179 (37.9%) developing stage-3 AKI. Male gender, black and Asian/Native American race, lower baseline estimated glomerular filtration rate (eGFR), higher body mass index (BMI), and higher Acute Physiology and Chronic Health Evaluation (APACHE) IV score were more prevalent among patients with severe AKI, as were systemic markers of inflammation. On multivariable analysis, male gender, black and Asian/Native American race, higher APACHE IV score, lower baseline eGFR, and higher BMI (mainly the highest BMI stratum ≥35 kg/m2) were independently associated with higher stages of AKI severity. Male gender, lower baseline eGFR, and higher APACHE IV score were also independently associated with the composite of RRT or in-hospital death. Moderate-to-severe AKI and severe AKI were independently associated with in-hospital death, and there was a significant interaction between BMI and moderate-to-severe AKI for the outcome of in-hospital death. Among 83 (18.1%) patients who required RRT, 27 (32.5%) survived, and 12 (44.4%) remained dialysis-dependent at discharge. At 3 and 6 months, 5 (41.7%) and 4 (33.3%) remained dialysis-dependent, respectively. CONCLUSIONS: AKI is common in critically ill adults with COVID-19. Several patient-level risk factors are associated with higher stages of AKI severity. BMI might be an effect modifier of AKI severity for in-hospital death. Among AKI survivors, there is a high rate of short- and long-term dialysis dependence.


Asunto(s)
Lesión Renal Aguda , COVID-19 , Humanos , Masculino , COVID-19/complicaciones , Mortalidad Hospitalaria , Estudios Retrospectivos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia
4.
Res Pract Thromb Haemost ; 6(2): e12669, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35341072

RESUMEN

Background: Few therapies exist to treat severe COVID-19 respiratory failure once it develops. Given known diffuse pulmonary microthrombi on autopsy studies of COVID-19 patients, we hypothesized that tissue plasminogen activator (tPA) may improve pulmonary function in COVID-19 respiratory failure. Methods: A multicenter, retrospective, observational study of patients with confirmed COVID-19 and severe respiratory failure who received systemic tPA (alteplase) was performed. Seventy-nine adults from seven medical centers were included in the final analysis after institutional review boards' approval; 23 were excluded from analysis because tPA was administered for pulmonary macroembolism or deep venous thrombosis. The primary outcome was improvement in the PaO2/FiO2 ratio from baseline to 48 h after tPA. Linear mixed modeling was used for analysis. Results: tPA was associated with significant PaO2/FiO2 improvement at 48 h (estimated paired difference = 23.1 ± 6.7), which was sustained at 72 h (interaction term p < 0.00). tPA administration was also associated with improved National Early Warning Score 2 scores at 24, 48, and 72 h after receiving tPA (interaction term p = 0.00). D-dimer was significantly elevated immediately after tPA, consistent with lysis of formed clot. Patients with declining respiratory status preceding tPA administration had more marked improvement in PaO2/FiO2 ratios than those who had poor but stable (not declining) respiratory status. There was one intracranial hemorrhage, which occurred within 24 h following tPA administration. Conclusions: These data suggest tPA is associated with significant improvement in pulmonary function in severe COVID-19 respiratory failure, especially in patients whose pulmonary function is in decline, and has an acceptable safety profile in this patient population.

5.
J Trauma Acute Care Surg ; 89(3): 453-457, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32427773

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented stresses on modern medical systems, overwhelming the resource infrastructure in numerous countries while presenting a unique series of pathophysiologic clinical findings. Thrombotic coagulopathy is common in critically ill patients suffering from COVID-19, with associated high rates of respiratory failure requiring prolonged periods of mechanical ventilation. Here, we report a case series of five patients suffering from profound, medically refractory COVID-19-associated respiratory failure who were treated with fibrinolytic therapy using tissue plasminogen activator (tPA; alteplase). All five patients appeared to have an improved respiratory status following tPA administration: one patient had an initial marked improvement that partially regressed after several hours, one patient had transient improvements that were not sustained, and three patients had sustained clinical improvements following tPA administration. LEVEL OF EVIDENCE: Therapeutic, Level V.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/complicaciones , Enfermedad Crítica/terapia , Neumonía Viral/complicaciones , Respiración Artificial/métodos , Insuficiencia Respiratoria/terapia , Terapia Trombolítica/métodos , Activador de Tejido Plasminógeno/uso terapéutico , Adulto , Anciano , COVID-19 , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/terapia , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/terapia , Insuficiencia Respiratoria/etiología , SARS-CoV-2
6.
IDCases ; 17: e00539, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31384556

RESUMEN

Leukocytoclastic vasculitis (LCV) refers to a histopathological pattern of neutrophil predominant inflammatory process of small vessels associated with fibrinoid necrosis. Cutaneous LCV usually presents as symmetrically distributed palpable purpuric nodules of the lower extremities with or without systemic involvement. Although 50% of LCV cases are idiopathic, it can be secondary to identifiable causes such as malignancy, autoimmune conditions, infections, and medications. Medications have been implicated in up to 25% of cases; sulfonamides, NSAIDs, and beta-lactams have the most frequent association. We herein present a 32-year-old female who developed palpable purpura over hands and lower limbs 12 days after exposure to oxacillin administered for infective endocarditis. Punch biopsy from the skin lesions confirmed the diagnosis of LCV. Given the temporal relationship between oxacillin administration and development of skin findings, the diagnosis of oxacillin-associated LCV was suspected. Discontinuation of drug resulted in resolution of the lesions confirming the diagnosis. To our knowledge, this is the second case of oxacillin-induced cutaneous LCV described in literature.

7.
J Intensive Care Med ; 30(8): 518-20, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25680979

RESUMEN

BACKGROUND: Thyroid storm is a rare, life-threatening condition which arises in patients with thyrotoxicosis, with an annual incidence of 2 patients per 1,000,000 and a mortality rate of 11%. CASE: We present the case of a 46-year-old-female with a medical history of controlled mild intermittent asthma, who presented with a severe asthma exacerbation, that triggered thyroid storm after exposure to polyurethane fumes. CONCLUSION: This patient represents, to the best of our knowledge, the first patient in whom the stress related to a severe asthma attack triggered the development of thyroid storm. She also is the first patient with no indication of cardiac dysfunction who developed fatal cardiac arrest after initiation of b-blockade for treatment of thyroid storm.


Asunto(s)
Disnea/inducido químicamente , Paro Cardíaco/inducido químicamente , Exposición por Inhalación/efectos adversos , Insuficiencia Multiorgánica/inducido químicamente , Poliuretanos/efectos adversos , Crisis Tiroidea/inducido químicamente , Antagonistas Adrenérgicos beta/administración & dosificación , Antagonistas Adrenérgicos beta/efectos adversos , Antitiroideos/administración & dosificación , Resultado Fatal , Femenino , Paro Cardíaco/fisiopatología , Paro Cardíaco/terapia , Humanos , Metimazol/administración & dosificación , Persona de Mediana Edad , Insuficiencia Multiorgánica/fisiopatología , Insuficiencia Multiorgánica/terapia , Yoduro de Potasio/administración & dosificación , Propranolol/administración & dosificación , Propranolol/efectos adversos , Resucitación , Crisis Tiroidea/tratamiento farmacológico , Crisis Tiroidea/fisiopatología
8.
Semin Immunol ; 26(6): 497-511, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25453227

RESUMEN

Mycobacterium tuberculosis has succeeded in infecting one-third of the human race though inhibition or evasion of innate and adaptive immunity. The pathogen is a facultative intracellular parasite that uses the niche provided by mononuclear phagocytes for its advantage. Complex interactions determine whether the bacillus will or will not be delivered to acidified lysosomes, whether the host phagocyte will survive infection or die, and whether the timing and mode of cell death works to the advantage of the host or the pathogen. Here we discuss cell death and autophagy in TB. These fundamental processes of cell biology feature in all aspects of TB pathogenesis and may be exploited to the treatment or prevention of TB disease.


Asunto(s)
Apoptosis/inmunología , Autofagia/inmunología , Evasión Inmune , Macrófagos/inmunología , Mycobacterium tuberculosis/inmunología , Tuberculosis Pulmonar/inmunología , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/inmunología , Proteínas Bacterianas/genética , Proteínas Bacterianas/inmunología , Regulación de la Expresión Génica , Humanos , Inmunidad Innata , Macrófagos/microbiología , Macrófagos/patología , Necrosis/genética , Necrosis/inmunología , Necrosis/microbiología , Necrosis/patología , Perforina/genética , Perforina/inmunología , Fagosomas/inmunología , Fagosomas/microbiología , Fagosomas/patología , Transducción de Señal , Tuberculosis Pulmonar/genética , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/patología
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