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1.
N Am Spine Soc J ; 17: 100308, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38264152

RESUMEN

Background: Spinal epidural abscesses (SEAs) are a devastating condition with high levels of associated morbidity and mortality. Hounsfield units (HUs), a marker of radiodensity on CT scans, have previously been correlated with adverse events following spinal interventions. We evaluated whether HUs might also be associated with all-cause complications and/or mortality in this high-risk population. Methods: This retrospective cohort study was carried out within an academic health system in the United States. Adults diagnosed with a SEA between 2006 and 2021 and who also had a CT scan characterizing their SEA within 6 months of diagnosis were considered. HUs were abstracted from the 4 vertebral bodies nearest to, but not including, the infected levels. Our primary outcome was the presence of composite 90-day complications and HUs represented the primary predictor. A multivariable logistic regression analysis was conducted adjusting for demographic and disease-specific confounders. In sensitivity testing, separate logistic regression analyses were conducted (1) in patients aged 65 and older and (2) with mortality as the primary outcome. Results: Our cohort consisted of 399 patients. The overall incidence of 90-day complications was 61.2% (n=244), with a 7.8% (n=31) 90-day mortality rate. Those experiencing complications were more likely to have undergone surgery to treat their SEA (58.6% vs. 46.5%; p=.018) but otherwise the cohorts were similar. HUs were not associated with composite 90-day complications (Odds ratio [OR] 1.00 [95% CI 1.00-1.00]; p=.842). Similar findings were noted in sensitivity testing. Conclusions: While HUs have previously been correlated with adverse events in certain clinical contexts, we found no evidence to suggest that HUs are associated with all-cause complications or mortality in patients with SEAs. Future research hoping to leverage 3-dimensional imaging as a prognostic measure in this patient population should focus on alternative targets. Level of Evidence: Level III; Observational Cohort study.

2.
Sci Rep ; 14(1): 1432, 2024 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-38228721

RESUMEN

Over the last decade, various efforts have been made to curtail the opioid crisis. The impact of these efforts, since the onset of the COVID-19 pandemic, has not been well characterized. We sought to develop national estimates of the prevalence of sustained prescription opioid use for a time period spanning the COVID-19 pandemic (2017-2021). We used TRICARE claims data (fiscal year 2017-2021) to identify patients who were prescription opioid non-users prior to receipt of a new opioid medication. We evaluated eligible patients for subsequent sustained prescription opioid use. The prevalence of sustained prescription opioid use during 2020-2021 was compared to 2017-2019. We performed multivariable logistic regression analyses to adjust for confounding. We performed secondary analyses that accounted for interactions between the time period and age, as well as a proxy for socioeconomic status. We determined there was a 68% reduction in the odds of sustained prescription opioid use (OR 0.32; 95% CI 0.27, 0.38; p < 0.001) in 2020-2021 as compared to 2017-2019. Significant reductions were identified across all US census divisions and all patient age groups. In both time periods, the plurality of encounters associated with initial receipt of an opioid that culminated in sustained prescription opioid use were associated with non-specific primary diagnoses. We found significant reductions in sustained prescription opioid use in 2020-2021 as compared to 2017-2019. The persistence of prescribing behaviors that result in issue of opioids for poorly characterized conditions remains an area of concern.


Asunto(s)
COVID-19 , Trastornos Relacionados con Opioides , Femenino , Humanos , Analgésicos Opioides/uso terapéutico , Pandemias , Trastornos Relacionados con Opioides/epidemiología , Trastornos Relacionados con Opioides/tratamiento farmacológico , Prescripciones de Medicamentos , COVID-19/epidemiología , Pautas de la Práctica en Medicina
3.
Am J Emerg Med ; 76: 273.e5-273.e7, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38097490

RESUMEN

Consumption of alkaline electrolyzed water (AEW) has become increasingly popular for consumer use. Although these alkaline water products are now commonly used, they are of questionable health benefit. Some individuals believe that it may help their dyspepsia. Furthermore, there is a paucity of evidence on its toxicologic profile and adverse effects. This is a single case report of a 42-year-old female with a past medical history of gestational diabetes, necrotizing pancreatitis, presented to the Emergency Department for 3 weeks of lethargy, weakness, difficulty walking, and vomiting. She endorsed consuming 5  liters (L) of alkaline water daily for the past month. Initial labs showed pH 7.69, potassium 1.6meQ/L, sodium 133 meQ/L, chloride 65 mmol/L, magnesium 0.9 meQ/L, and bicarbonate 46 mmol/L, and lactate of 13.2 mmol/L. EKG showed sinus tachycardia with QTc of 630 milliseconds. Patient was treated supportively with intravenous fluids and electrolyte replacement. The potassium rose to 6.6 meQ/L, which then the patient was treated for hyperkalemia. After four days of intravenous fluid and electrolyte replacement, the patient's electrolytes and acid-base status normalized, and she was transferred to the medical floors for further management. This case report illustrates severe metabolic alkalosis and hypokalemia in the setting of chronic alkaline water exposure. It also is an example of alkalemia with hyperlactatemia, or "lactic alkalosis". To our knowledge, there is no previous literature reporting serious adverse effects of alkaline bottled water products.


Asunto(s)
Alcalosis , Hipopotasemia , Femenino , Humanos , Adulto , Hipopotasemia/etiología , Hipopotasemia/terapia , Alcalosis/complicaciones , Electrólitos , Potasio , Agua
4.
J Bone Joint Surg Am ; 105(18): 1403-1409, 2023 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-37410854

RESUMEN

BACKGROUND: The Stopping Opioids after Surgery (SOS) score was developed to identify patients at risk for sustained opioid use following surgery. The SOS score has not been specifically validated for patients in a general orthopaedic context. Our primary objective was to validate the SOS score within this context. METHODS: In this retrospective cohort study, we considered a broad array of representative orthopaedic procedures performed between January 1, 2018, and March 31, 2022. These procedures included rotator cuff repair, lumbar discectomy, lumbar fusion, total knee and total hip arthroplasty, open reduction and internal fixation (ORIF) of ankle fracture, ORIF of distal radial fracture, and anterior cruciate ligament reconstruction. The performance of the SOS score was evaluated by calculating the c-statistic, receiver operating characteristic curve, and the observed rates of sustained prescription opioid use (defined as uninterrupted prescriptions of opioids for ≥90 days) following surgery. For our sensitivity analysis, we compared these metrics among various time epochs related to the COVID-19 pandemic. RESULTS: A total of 26,114 patients were included, of whom 51.6% were female and 78.1% were White. The median age was 63 years. The observed prevalence of sustained opioid use was 1.3% (95% confidence interval [CI], 1.2% to 1.5%) in the low-risk group (SOS score of <30), 7.4% (95% CI, 6.9% to 8.0%) in the medium-risk group (SOS score of 30 to 60), and 20.8% (95% CI, 17.7% to 24.2%) in the high-risk group (SOS score of >60). The performance of the SOS score in the overall group was strong, with a c-statistic of 0.82. The performance of the SOS score showed no evidence of worsening over time. The c-statistic was 0.79 before the COVID-19 pandemic and ranged from 0.77 to 0.80 throughout the waves of the pandemic. CONCLUSIONS: We validated the use of the SOS score for sustained prescription opioid use following a diverse array of orthopaedic procedures across subspecialties. This tool is easy to implement for the purpose of prospectively identifying patients in musculoskeletal service lines who are at higher risk for sustained opioid use, thereby enabling the future implementation of upstream interventions and modifications to avert opioid abuse and to combat the opioid epidemic. LEVEL OF EVIDENCE: Diagnostic Level III . See Instructions for Authors for a complete description of levels of evidence.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , COVID-19 , Trastornos Relacionados con Opioides , Ortopedia , Humanos , Femenino , Persona de Mediana Edad , Masculino , Analgésicos Opioides/uso terapéutico , Estudios Retrospectivos , Pandemias , Dolor Postoperatorio/etiología , COVID-19/epidemiología , Trastornos Relacionados con Opioides/epidemiología , Trastornos Relacionados con Opioides/prevención & control , Prescripciones , Discectomía/efectos adversos
5.
West J Emerg Med ; 24(3): 405-415, 2023 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-37278789

RESUMEN

INTRODUCTION: Limited information exists on patients with suspected coronavirus disease 2019 (COVID-19) who return to the emergency department (ED) during the first wave. In this study we aimed to identify predictors of ED return within 72 hours for patients with suspected COVID-19. METHODS: Incorporating data from 14 EDs within an integrated healthcare network in the New York metropolitan region from March 2-April 27, 2020, we analyzed this data on predictors for a return ED visit-including demographics, comorbidities, vital signs, and laboratory results. RESULTS: In total, 18,599 patients were included in the study. The median age was 46 years old [interquartile range 34-58]), 50.74% were female, and 49.26% were male. Overall, 532 (2.86%) returned to the ED within 72 hours, and 95.49% were admitted at the return visit. Of those tested for COVID-19, 59.24% (4704/7941) tested positive. Patients with chief complaints of "fever" or "flu" or a history of diabetes or renal disease were more likely to return at 72 hours. Risk of return increased with persistently abnormal temperature (odds ratio [OR] 2.43, 95% CI 1.8-3.2), respiratory rate (2.17, 95% CI 1.6-3.0), and chest radiograph (OR 2.54, 95% CI 2.0-3.2). Abnormally high neutrophil counts, low platelet counts, high bicarbonate values, and high aspartate aminotransferase levels were associated with a higher rate of return. Risk of return decreased when discharged on antibiotics (OR 0.12, 95% CI 0.0-0.3) or corticosteroids (OR 0.12, 95% CI 0.0-0.9). CONCLUSION: The low overall return rate of patients during the first COVID-19 wave indicates that physicians' clinical decision-making successfully identified those acceptable for discharge.


Asunto(s)
COVID-19 , Alta del Paciente , Humanos , Masculino , Femenino , Persona de Mediana Edad , Readmisión del Paciente , COVID-19/epidemiología , Hospitalización , Servicio de Urgencia en Hospital , Estudios Retrospectivos
6.
Am J Respir Crit Care Med ; 208(5): 570-578, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37364280

RESUMEN

Rationale: Kidney injury is common and associated with worse outcomes in patients with septic shock. Mitochondrial resuscitation with thiamine (vitamin B1) may attenuate septic kidney injury. Objectives: To assess whether thiamine supplementation attenuates kidney injury in septic shock. Methods: The TRPSS (Thiamine for Renal Protection in Septic Shock) trial was a multicenter, randomized, placebo-controlled trial of thiamine versus placebo in septic shock. The primary outcome was change in serum creatinine between enrollment and 72 hours after enrollment. Measurements and Main Results: Eighty-eight patients were enrolled (42 patients received the intervention, and 46 received placebo). There was no significant between-groups difference in creatinine at 72 hours (mean difference, -0.57 mg/dl; 95% confidence interval, -1.18, 0.04; P = 0.07). There was no difference in receipt of kidney replacement therapy (14.3% vs. 21.7%, P = 0.34), acute kidney injury (as defined by stage 3 of the Kidney Disease: Improving Global Outcomes acute kidney injury scale; 54.7% vs. 73.9%, P = 0.07), or mortality (35.7% vs. 54.3%, P = 0.14) between the thiamine and placebo groups. Patients who received thiamine had more ICU-free days (median [interquartile range]: 22.5 [0.0-25.0] vs. 0.0 [0.0-23.0], P < 0.01). In the thiamine-deficient cohort (27.4% of patients), there was no difference in rates of kidney failure (57.1% thiamine vs. 81.5% placebo) or in-hospital mortality (28.6% vs. 68.8%) between groups. Conclusions: In the TRPSS trial, there was no statistically significant difference in the primary outcome of change in creatinine over time. Patients who received thiamine had more ICU-free days, but there was no difference in other secondary outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT03550794).


Asunto(s)
Lesión Renal Aguda , Choque Séptico , Humanos , Tiamina/uso terapéutico , Choque Séptico/complicaciones , Choque Séptico/tratamiento farmacológico , Creatinina , Riñón , Lesión Renal Aguda/prevención & control , Lesión Renal Aguda/complicaciones
7.
Clin Orthop Relat Res ; 481(12): 2343-2351, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37159263

RESUMEN

BACKGROUND: The Stopping Opioids After Surgery (SOS) score is a validated tool that was developed to determine the risk of sustained opioid use after surgical interventions, including orthopaedic procedures. Despite prior investigations validating the SOS score in diverse contexts, its performance across racial, ethnic, and socioeconomic subgroups has not been assessed. QUESTIONS/PURPOSES: In a large, urban, academic health network, did the performance of the SOS score differ depending on (1) race and ethnicity or (2) socioeconomic status? METHODS: This retrospective investigation was conducted using data from an internal, longitudinally maintained registry of a large, urban, academic health system in the Northeastern United States. Between January 1, 2018, and March 31, 2022, we treated 26,732 adult patients via rotator cuff repair, lumbar discectomy, lumbar fusion, TKA, THA, ankle or distal radius open reduction and internal fixation, or ACL reconstruction. We excluded 1% of patients (274 of 26,732) because of missing length of stay information, 0.06% (15) for missing discharge information, 1% (310) for missing medication information related to loss to follow-up, and 0.07% (19) who died during their hospital stay. Based on these inclusion and exclusion criteria, 26,114 adult patients were left for analysis. The median age in our cohort was 63 years (IQR 52 to 71), and most patients were women (52% [13,462 of 26,114]). Most patients self-reported their race and ethnicity as non-Hispanic White (78% [20,408 of 26,114]), but the cohort also included non-Hispanic Black (4% [939]), non-Hispanic Asian (2% [638]), and Hispanic (1% [365]) patients. Five percent (1295) of patients were of low socioeconomic status, defined by prior SOS score investigations as patients with Medicaid insurance. Components of the SOS score and the observed frequency of sustained postoperative opioid prescriptions were abstracted. The performance of the SOS score was compared across racial, ethnic, and socioeconomic subgroups using the c-statistic, which measures the capacity of the model to differentiate between patients with and without sustained opioid use. This measure should be interpreted on a scale between 0 and 1, where 0 represents a model that perfectly predicts the wrong classification, 0.5 represents performance no better than chance, and 1.0 represents perfect discrimination. Scores less than 0.7 are generally considered poor. The baseline performance of the SOS score in past investigations has ranged from 0.76 to 0.80. RESULTS: The c-statistic for non-Hispanic White patients was 0.79 (95% CI 0.78 to 0.81), which fell within the range of past investigations. The SOS score performed worse for Hispanic patients (c-statistic 0.66 [95% CI 0.52 to 0.79]; p < 0.001), where it tended to overestimate patients' risks of sustained opioid use. The SOS score for non-Hispanic Asian patients did not perform worse than in the White patient population (c-statistic 0.79 [95% CI 0.67 to 0.90]; p = 0.65). Similarly, the degree of overlapping CIs suggests that the SOS score did not perform worse in the non-Hispanic Black population (c-statistic 0.75 [95% CI 0.69 to 0.81]; p = 0.003). There was no difference in score performance among socioeconomic groups (c-statistic 0.79 [95% CI 0.74 to 0.83] for socioeconomically disadvantaged patients; 0.78 [95% CI 0.77 to 0.80] for patients who were not socioeconomically disadvantaged; p = 0.92). CONCLUSION: The SOS score performed adequately for non-Hispanic White patients but performed worse for Hispanic patients, where the 95% CI nearly included an area under the curve value of 0.5, suggesting that the tool is no better than chance at predicting sustained opioid use for Hispanic patients. In the Hispanic population, it commonly overestimated the risk of opioid dependence. Its performance did not differ among patients of different sociodemographic backgrounds. Future studies might seek to contextualize why the SOS score overestimates expected opioid prescriptions for Hispanic patients and how the utility performs among more specific Hispanic subgroups. CLINICAL RELEVANCE: The SOS score is a valuable tool in ongoing efforts to combat the opioid epidemic; however, disparities exist in terms of its clinical applicability. Based on this analysis, the SOS score should not be used for Hispanic patients. Additionally, we provide a framework for how other predictive models should be tested in various lesser-represented populations before implementation.


Asunto(s)
Analgésicos Opioides , Trastornos Relacionados con Opioides , Factores Socioeconómicos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Analgésicos Opioides/uso terapéutico , Etnicidad , Trastornos Relacionados con Opioides/epidemiología , Trastornos Relacionados con Opioides/prevención & control , Estudios Retrospectivos , Estados Unidos , Grupos Raciales
8.
Spine J ; 23(6): 791-798, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36870450

RESUMEN

BACKGROUND CONTEXT: The use of intraoperative CT has continued to grow in recent years, as various techniques leverage the promise of improved instrumentation accuracy and the hope for decreased complications. Nonetheless, the literature regarding the short- and long-term complications associated with such techniques remains scant and/or confounded by indication and selection bias. PURPOSE: To use causal inference techniques to determine whether intraoperative CT use is associated with an improved complication profile as compared to conventional radiography for single-level lumbar fusions, an increasingly commonplace application for this technology. STUDY DESIGN/SETTING: Inverse probability weighted retrospective cohort study carried out within a large integrated health care network. PATIENT SAMPLE: Adult patients who underwent surgical treatment of spondylolisthesis via lumbar fusion from January 2016 to December 2021. OUTCOME MEASURES: Our primary outcome was the incidence rate of revision surgery. Our secondary outcome was the incidence of composite 90-day complications (deep and superficial surgical site infection, venous thromboembolic events, and unplanned readmissions). METHODS: Demographics, intraoperative information, and postoperative complications were abstracted from electronic health records. A propensity score was developed utilizing a parsimonious model to account for covariate interaction with our primary predictor, intraoperative imaging technique. This propensity score was utilized in the creation of inverse probability weights to adjust for indication and selection bias. The rate of revisions within 3 years as well as the rate of revisions at any time-point were compared between cohorts using Cox regression analysis. The incidence of composite 90-day complications were compared using negative binomial regression. RESULTS: Our patient population consisted of 583 patients, with 132 who underwent intraoperative CT and 451 who underwent conventional radiographic techniques. There were no significant differences between cohorts following inverse probability weighting. No significant differences were detected in 3-year revision rates (HR, 0.74 [95% CI 0.29, 1.92]; p=.5), overall revision rates (HR, 0.54 [95% CI 0.20, 1.46]; p=.2), or 90-day complications (RC -0.24 [95% CI -1.35, 0.87]; p=.7). CONCLUSIONS: Intraoperative CT use was not associated with an improved complication profile in either the short- or long-term for patients undergoing single-level instrumented fusion. This observed clinical equipoise should be weighed against resource and radiation-related costs when considering intraoperative CT for low complexity fusions.


Asunto(s)
Vértebras Lumbares , Fusión Vertebral , Adulto , Humanos , Estudios Retrospectivos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Fusión Vertebral/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
9.
Sci Adv ; 9(5): eadf4313, 2023 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-36735789

RESUMEN

Antibody-based strategies have been attempted to antagonize early cytokines of sepsis, but not yet been tried to target inducible late-acting mediators. Here, we report that the expression and secretion of procathepsin-L (pCTS-L) was induced by serum amyloid A (SAA) in innate immune cells, contributing to its late and systemic accumulation in experimental and clinical sepsis. Recombinant pCTS-L induced interleukin-6 (IL-6), IL-8, GRO-α/KC, GRO-ß/MIP-2, and MCP-1 release in innate immune cells and moderately correlated with blood concentrations of these cytokines/chemokines in clinical sepsis. Mechanistically, pCTS-L interacted with Toll-like receptor 4 (TLR4) and the receptor for advanced glycation end products (RAGE) to induce cytokines/chemokines. Pharmacological suppression of pCTS-L with neutralizing polyclonal and monoclonal antibodies attenuated pCTS-L-mediated inflammation by impairing its interaction with TLR4 and RAGE receptors, and consequently rescued animals from lethal sepsis. Our findings have suggested a possibility of developing antibody strategies to prevent dysregulated immune responses mediated by late-acting cytokines.


Asunto(s)
Sepsis , Receptor Toll-Like 4 , Animales , Receptor Toll-Like 4/metabolismo , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Citocinas , Receptor para Productos Finales de Glicación Avanzada , Quimiocinas/metabolismo
10.
Cureus ; 14(11): e31086, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36475114

RESUMEN

Introduction Treatment with dexamethasone reduces mortality in patients with coronavirus disease 2019 (COVID-19) pneumonia requiring supplemental oxygen, but the optimal dose has not been determined. Objective To determine whether weight-based dexamethasone of 0.2 mg/kg is superior to 6 mg daily in reducing 28-day mortality in patients with COVID-19 and hypoxemia. Materials and methods A multicenter, open-label, randomized clinical trial was conducted between March 2021 and December 2021 at seven hospitals within Northwell Health. A total of 142 patients with confirmed COVID-19 and hypoxemia were included. Participants were randomized in a 1:1 ratio to dexamethasone 0.2 mg/kg intravenously daily (n = 70) or 6 mg daily (n = 72) for up to 10 days. Results There was no statistically significant difference in the primary outcome of 28-day all-cause mortality with deaths in 12 of 70 patients (17.14%) in the intervention group and 15 of 72 patients (20.83%) in the control group (p = 0.58). There were no statistically significant differences among the secondary outcomes. Conclusion In patients with COVID-19 and hypoxemia, the use of weight-based dexamethasone dosing was not superior to dexamethasone 6 mg in reducing all-cause mortality at 28 days. Clinical trial registration This study was registered under ClinicalTrials.gov (identifier: NCT04834375).

11.
Ann Am Thorac Soc ; 19(8): 1346-1354, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35213292

RESUMEN

Rationale: During the first wave of the coronavirus disease (COVID-19) pandemic in New York City, the number of mechanically ventilated COVID-19 patients rapidly surpassed the capacity of traditional intensive care units (ICUs), resulting in health systems utilizing other areas as expanded ICUs to provide critical care. Objectives: To evaluate the mortality of patients admitted to expanded ICUs compared with those admitted to traditional ICUs. Methods: Multicenter, retrospective, cohort study of mechanically ventilated patients with COVID-19 admitted to the ICUs at 11 Northwell Health hospitals in the greater New York City area between March 1, 2020 and April 30, 2020. Primary outcome was in-hospital mortality up to 28 days after intubation of COVID-19 patients. Results: Among 1,966 mechanically ventilated patients with COVID-19, 1,198 (61%) died within 28 days after intubation, 46 (2%) were transferred to other hospitals outside of the Northwell Health system, 722 (37%) survived in the hospital until 28 days or were discharged after recovery. The risk of mortality of mechanically ventilated patients admitted to expanded ICUs was not different from those admitted to traditional ICUs (hazard ratio [HR], 1.07; 95% confidence interval [CI], 0.95-1.20; P = 0.28), while hospital occupancy for critically ill patients itself was associated with increased risk of mortality (HR, 1.28; 95% CI, 1.12-1.45; P < 0.001). Conclusions: Although increased hospital occupancy for critically ill patients itself was associated with increased mortality, the risk of 28-day in-hospital mortality of mechanically ventilated patients with COVID-19 who were admitted to expanded ICUs was not different from those admitted to traditional ICUs.


Asunto(s)
COVID-19 , Enfermedad Crítica , COVID-19/terapia , Estudios de Cohortes , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Ciudad de Nueva York/epidemiología , Respiración Artificial , Estudios Retrospectivos
12.
JAMA ; 324(7): 642-650, 2020 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-32809003

RESUMEN

IMPORTANCE: The combination of ascorbic acid, corticosteroids, and thiamine has been identified as a potential therapy for septic shock. OBJECTIVE: To determine whether the combination of ascorbic acid, corticosteroids, and thiamine attenuates organ injury in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTS: Randomized, blinded, multicenter clinical trial of ascorbic acid, corticosteroids, and thiamine vs placebo for adult patients with septic shock. Two hundred five patients were enrolled between February 9, 2018, and October 27, 2019, at 14 centers in the United States. Follow-up continued until November 26, 2019. INTERVENTIONS: Patients were randomly assigned to receive parenteral ascorbic acid (1500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days (n = 103) or placebo in matching volumes at the same time points (n = 102). MAIN OUTCOMES AND MEASURES: The primary outcome was change in the Sequential Organ Failure Assessment (SOFA) score (range, 0-24; 0 = best) between enrollment and 72 hours. Key secondary outcomes included kidney failure and 30-day mortality. Patients who received at least 1 dose of study drug were included in analyses. RESULTS: Among 205 randomized patients (mean age, 68 [SD, 15] years; 90 [44%] women), 200 (98%) received at least 1 dose of study drug, completed the trial, and were included in the analyses (101 with intervention and 99 with placebo group). Overall, there was no statistically significant interaction between time and treatment group with regard to SOFA score over the 72 hours after enrollment (mean SOFA score change from 9.1 to 4.4 [-4.7] points with intervention vs 9.2 to 5.1 [-4.1] points with placebo; adjusted mean difference, -0.8; 95% CI, -1.7 to 0.2; P = .12 for interaction). There was no statistically significant difference in the incidence of kidney failure (31.7% with intervention vs 27.3% with placebo; adjusted risk difference, 0.03; 95% CI, -0.1 to 0.2; P = .58) or in 30-day mortality (34.7% vs 29.3%, respectively; hazard ratio, 1.3; 95% CI, 0.8-2.2; P = .26). The most common serious adverse events were hyperglycemia (12 patients with intervention and 7 patients with placebo), hypernatremia (11 and 7 patients, respectively), and new hospital-acquired infection (13 and 12 patients, respectively). CONCLUSIONS AND RELEVANCE: In patients with septic shock, the combination of ascorbic acid, corticosteroids, and thiamine, compared with placebo, did not result in a statistically significant reduction in SOFA score during the first 72 hours after enrollment. These data do not support routine use of this combination therapy for patients with septic shock. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03389555.


Asunto(s)
Corticoesteroides/uso terapéutico , Ácido Ascórbico/uso terapéutico , Insuficiencia Multiorgánica/prevención & control , Choque Séptico/tratamiento farmacológico , Tiamina/uso terapéutico , Corticoesteroides/efectos adversos , Adulto , Anciano , Ácido Ascórbico/efectos adversos , Infección Hospitalaria , Quimioterapia Combinada , Femenino , Humanos , Hiperglucemia/inducido químicamente , Hipernatremia/inducido químicamente , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/etiología , Puntuaciones en la Disfunción de Órganos , Modelos de Riesgos Proporcionales , Choque Séptico/complicaciones , Tiamina/efectos adversos , Insuficiencia del Tratamiento
13.
Sci Transl Med ; 12(539)2020 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-32295901

RESUMEN

For the clinical management of sepsis, antibody-based strategies have only been attempted to antagonize proinflammatory cytokines but not yet been tried to target harmless proteins that may interact with these pathogenic mediators. Here, we report an antibody strategy to intervene in the harmful interaction between tetranectin (TN) and a late-acting sepsis mediator, high-mobility group box 1 (HMGB1), in preclinical settings. We found that TN could bind HMGB1 to reciprocally enhance their endocytosis, thereby inducing macrophage pyroptosis and consequent release of lactate dehydrogenase and apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain. The genetic depletion of TN expression or supplementation of exogenous TN protein at subphysiological doses distinctly affected the outcomes of potentially lethal sepsis, revealing a previously underappreciated beneficial role of TN in sepsis. Furthermore, the administration of domain-specific polyclonal and monoclonal antibodies effectively inhibited TN/HMGB1 interaction and endocytosis and attenuated the sepsis-induced TN depletion and tissue injury, thereby rescuing animals from lethal sepsis. Our findings point to a possibility of developing antibody strategies to prevent harmful interactions between harmless proteins and pathogenic mediators of human diseases.


Asunto(s)
Proteína HMGB1 , Lectinas Tipo C , Sepsis , Animales , Anticuerpos Monoclonales/uso terapéutico , Humanos , Sepsis/tratamiento farmacológico
14.
JMIR Med Inform ; 6(4): e44, 2018 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-30361200

RESUMEN

BACKGROUND: Use of computed tomography pulmonary angiography (CTPA) in the assessment of pulmonary embolism (PE) has markedly increased over the past two decades. While this technology has improved the accuracy of radiological testing for PE, CTPA also carries the risk of substantial iatrogenic harm. Each CTPA carries a 14% risk of contrast-induced nephropathy and a lifetime malignancy risk that can be as high as 2.76%. The appropriate use of CTPA can be estimated by monitoring the CTPA yield, the percentage of tests positive for PE. This is the first study to propose and validate a computerized method for measuring the CTPA yield in the emergency department (ED). OBJECTIVE: The objective of our study was to assess the validity of a novel computerized method of calculating the CTPA yield in the ED. METHODS: The electronic health record databases at two tertiary care academic hospitals were queried for CTPA orders completed in the ED over 1-month periods. These visits were linked with an inpatient admission with a discharge diagnosis of PE based on the International Classification of Diseases codes. The computerized the CTPA yield was calculated as the number of CTPA orders with an associated inpatient discharge diagnosis of PE divided by the total number of orders for completed CTPA. This computerized method was then validated by 2 independent reviewers performing a manual chart review, which included reading the free-text radiology reports for each CTPA. RESULTS: A total of 349 CTPA orders were completed during the 1-month periods at the two institutions. Of them, acute PE was diagnosed on CTPA in 28 studies, with a CTPA yield of 7.7%. The computerized method correctly identified 27 of 28 scans positive for PE. The one discordant scan was tied to a patient who was discharged directly from the ED and, as a result, never received an inpatient discharge diagnosis. CONCLUSIONS: This is the first successful validation study of a computerized method for calculating the CTPA yield in the ED. This method for data extraction allows for an accurate determination of the CTPA yield and is more efficient than manual chart review. With this ability, health care systems can monitor the appropriate use of CTPA and the effect of interventions to reduce overuse and decrease preventable iatrogenic harm.

15.
Crit Care ; 22(1): 283, 2018 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-30373647

RESUMEN

The combination of thiamine, ascorbic acid, and hydrocortisone has recently emerged as a potential adjunctive therapy to antibiotics, infectious source control, and supportive care for patients with sepsis and septic shock. In the present manuscript, we provide a comprehensive review of the pathophysiologic basis and supporting research for each element of the thiamine, ascorbic acid, and hydrocortisone drug combination in sepsis. In addition, we describe potential areas of synergy between these therapies and discuss the strengths/weaknesses of the two studies to date which have evaluated the drug combination in patients with severe infection. Finally, we describe the current state of current clinical practice as it relates to the thiamine, ascorbic acid, and hydrocortisone combination and present an overview of the randomized, placebo-controlled, multi-center Ascorbic acid, Corticosteroids, and Thiamine in Sepsis (ACTS) trial and other planned/ongoing randomized clinical trials.


Asunto(s)
Corticoesteroides/uso terapéutico , Ácido Ascórbico/uso terapéutico , Sepsis/tratamiento farmacológico , Tiamina/uso terapéutico , Corticoesteroides/farmacología , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Ácido Ascórbico/farmacología , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Humanos , Hidrocortisona/farmacología , Hidrocortisona/uso terapéutico , Modelos Biológicos , Tiamina/farmacología
16.
Chest ; 154(1): e23-e26, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-30044750

RESUMEN

CASE PRESENTATION: A 61-year-old Caribbean man presented to the ED with dyspnea that had progressed over the previous week with associated cough and high fevers. Four days prior to admission, his primary care physician noted oral thrush and obtained a chest radiograph that revealed a right middle lobe infiltrate. He was prescribed levofloxacin and clotrimazole. Despite therapy, his symptoms progressed. He had an 11 pack-year smoking history and hypertension but had been in good health. He denied recent travel, alcohol or illicit drug use, or high-risk sexual behaviors, and his only previous medicine was amlodipine. Institutional review board approval was not obtained for this case report, as all patient data are anonymous and obtained during routine patient care activities.


Asunto(s)
Anticuerpos Antivirales/análisis , Infecciones por Deltaretrovirus/complicaciones , Leucemia de Células T/complicaciones , Virus Linfotrópico T Tipo 1 de los Primates/inmunología , Insuficiencia Respiratoria/etiología , Infecciones Tumorales por Virus/complicaciones , Biopsia , Broncoscopía , Región del Caribe , Infecciones por Deltaretrovirus/diagnóstico , Infecciones por Deltaretrovirus/virología , Diagnóstico Diferencial , Humanos , Leucemia de Células T/diagnóstico , Leucemia de Células T/virología , Masculino , Persona de Mediana Edad , Insuficiencia Respiratoria/diagnóstico , Tomografía Computarizada por Rayos X , Infecciones Tumorales por Virus/diagnóstico , Infecciones Tumorales por Virus/virología
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