Direct Oral Anticoagulant Reversal in the Pediatric Emergency Department.

ABSTRACT: Direct oral anticoagulants have been used in the adult population for years and are being used more frequently in pediatrics. Direct oral anticoagulants are chosen preferentially because they do not require close outpatient monitoring, have an equal or better safety profile, and are easy for patients to take. Warfarin is the previous, more commonly used oral anticoagulant and acts as a vitamin K antagonist. Direct oral anticoagulants mechanism of action is different in that they directly inhibit part of the coagulation cascade accomplishing the same end goal. Given their differing mechanisms, they require alternate medications for proper reversal when concerned about overdose of life-threatening bleeds. This review will outline the most commonly used direct oral anticoagulants in pediatric populations and the supporting (mainly adult) data available for proper reversal of these medications in times of need.

A fatal case of bortezomib-induced lung toxicity in a young adult heart transplant recipient.

Bortezomib is approved for the treatment of multiple myeloma but increasingly used in heart transplant (HTx) recipients with antibody-mediated rejection (AMR). Severe pulmonary toxicity is a rare complication in multiple myeloma patients treated with bortezomib, but has not been described in a solid organ transplant recipient. A 20-year-old man 7 years post-HTx presented with acute rejection with hemodynamic compromise. Endomyocardial biopsy showed mixed rejection (ISHLT grade 2R-3R acute cellular rejection (ACR) and pAMR 1 (I+) with diffuse C4d staining). Two new high MFI circulating MHC class-II donor-specific antibodies (DSA) were detected. Treatment included corticosteroids, antithymocyte globulin, plasmapheresis, IVIG, rituximab, and bortezomib (1.3 mg/m2 ). Due to rebound in DSA, a second course of bortezomib was started. Thrombocytopenia and peripheral neuropathy prompted a 50% dose reduction during the 2nd course. Shortly after the 3rd reduced dose, the patient developed hypoxemic respiratory failure. Bronchoscopy revealed pulmonary hemorrhage with negative infectious studies. Chest CT showed bilateral parenchymal disease with bronchiectasis and alveolar bleeding. Despite treatment with high-dose steroids, severe ARDS ensued with multisystem organ failure. The patient expired 23 days after the final dose of bortezomib. Post-mortem lung histology revealed diffuse alveolar damage, pulmonary fibrosis, and hemorrhage. Cardiac histology showed resolving/residual ACR 1R and pAMR 1 (I+). While rare, bortezomib-induced lung toxicity (BILT) can occur in HTx recipients and can carry a high risk of mortality. Drug reaction and immediate drug withdrawal should be considered in patients who develop respiratory symptoms, though optimal management of BILT is unclear.

An ISHLT consensus statement on strategies to prevent and manage hemocompatibility related adverse events in patients with a durable, continuous-flow ventricular assist device.

Life expectancy of patients with a durable, continuous-flow left ventricular assist device (CF-LVAD) continues to increase. Despite significant improvements in the delivery of care for patients with these devices, hemocompatability-related adverse events (HRAEs) are still a concern and contribute to significant morbility and mortality when they occur. As such, dissemination of current best evidence and practices is of critical importance. This ISHLT Consensus Statement is a summative assessment of the current literature on prevention and management of HRAEs through optimal management of oral anticoagulant and antiplatelet medications, parenteral anticoagulant medications, management of patients at high risk for HRAEs and those experiencing thrombotic or bleeding events, and device management outside of antithrombotic medications. This document is intended to assist clinicians caring for patients with a CF-LVAD provide the best care possible with respect to prevention and management of these events.

Genetic interaction in the association between oxidative stress and diabetes in the Spanish population.

Oxidative stress (OS) is a relevant intermediate mechanism involved in Type 2 Diabetes Mellitus (T2D) development. To date, the interaction between OS parameters and variations in genes related to T2D has not been analyzed. AIMS: To study the genetic interaction of genes potentially related to OS levels (redox homeostasis, renin-angiotensin-aldosterone system, endoplasmic stress response, dyslipidemia, obesity and metal transport) and OS and T2D risk in a general population from Spain (the Hortega Study) in relation to the risk of suffering from T2D. MATERIALS AND METHODS: One thousand five hundred and two adults from the University Hospital Rio Hortega area were studied and 900 single nucleotide polymorphisms (SNPs) from 272 candidate genes were analyzed. RESULTS: There were no differences in OS levels between cases and controls. Some polymorphisms were associated with T2D and with OS levels. Significant interactions were observed between OS levels and two polymorphisms in relation to T2D presence: rs196904 (ERN1 gene) and rs2410718 (COX7C gene); and between OS levels and haplotypes of the genes: SP2, HFF1A, ILI8R1, EIF2AK2, TXNRD2, PPARA, NDUFS2 and ERN1. CONCLUSIONS: Our results indicate that genetic variations of the studied genes are associated with OS levels and that their interaction with OS parameters may contribute to the risk of developing T2D in the Spanish general population. These data support the importance of analyzing the influence of OS levels and their interaction with genetic variations in order to establish their real impact in T2D risk. Further studies are required to identify the real relevance of interactions between genetic variations and OS levels and the mechanisms involved in them.

Sample Treatment with Trypsin for RT-LAMP COVID-19 Diagnosis.

The SARS-CoV-2 coronavirus is responsible for the COVID-19 pandemic resulting in a global health emergency. Given its rapid spread and high number of infected individuals, a diagnostic tool for a rapid, simple, and cost-effective detection was essential. In this work, we developed a COVID-19 diagnostic test, that incorporates a human internal control, based on the Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP). When working with synthetic SARS-CoV-2 RNA, the optimized RT-LAMP assay has a sensitivity of 10 viral copies and can be detected by fluorescence in less than 15 min or by the naked eye in 25 min using colorimetric RT-LAMP. To avoid the RNA extraction step, a pre-treatment of the sample was optimized. Subsequently, a validation was performed on 268 trypsin treated samples (including nasopharyngeal, buccal, and nasal exudates) and amplified with colorimetric RT-LAMP to evaluate its sensitivity and specificity in comparison with RT-qPCR of extracted samples. The validation results showed a sensitivity and specificity of 100% for samples with Ct ≤ 30. The rapid, simple, and inexpensive RT-LAMP SARS-CoV-2 extraction-free procedure developed may be an alternative test that could be applied for the detection of SARS-CoV-2 or adapted to detect other viruses present in saliva or nasopharyngeal samples with higher sensitivity and specificity of the antibody test.

Substance use screening and rates of treatment referral among justice-involved youth.

BACKGROUND: Justice-involved youth report high rates of substance use and related problems that are associated with treatment needs; however, data on screening and linkage to treatment within the justice system is lacking. To further inform the juvenile justice behavioral health cascade of care, this study examined factors associated with identified problematic substance use and treatment referral using two screening tools. METHOD: As part of a family court intake process, 348 justice-involved youth received two screening measures, the MAYSI-2 alcohol/drug use subscale and the CRAFFT. Both tools are designed to indicate early warning signs of substance use problems and signal referral for further clinical evaluation or treatment. Chart review analysis examined whether demographic variables (sex & race), severity of use, and type of substance used were associated with positive screens on either or both measures and subsequent treatment referral. RESULTS: Half (51.2%) of youth were identified as having problematic substance use (a positive screen) on at least one of the screeners. Overall, 38.5% positively screened on the CRAFFT with only 0.3% positively screening on just the MAYSI-2 alcohol/drug scale. Cannabis only users were less likely to positively screen on the MAYSI-2 compared to youth who reported use of both alcohol and cannabis. Positively screening on one versus both screeners was not associated with referral, yet many (28%) who positively screened were not referred for services. CONCLUSIONS: The CRAFFT may be more accurate at identifying youth specifically at risk for problematic cannabis use compared to the MAYSI-2 alcohol/drug subscale. Regardless of tool used, treatment referral was low, highlighting the need for accurate identification of treatment needs of substance-using, justice-involved youth. Interventions to facilitate referrals for youth with problematic substance use are needed.

The nutritional status of the elderly patient infected with COVID-19: the forgotten risk factor?

BACKGROUND: Since the first cases of COVID-19 were reported in Wuhan, the nutritional status of individuals infected with the virus has not been included in the risk profiles prepared. However, nutritional status, along with other factors, is decisive in the evolution of patients with other infectious diseases. The nutritional status of individuals is considered an indicator of health status. Furthermore, optimal nutritional status transcends the individual, and poor diet in a population can be considered a group risk factor. Evidence exists on the influence that diet has on the immune system and susceptibility to disease. OBJECTIVE: To evaluate the nutritional status of patients older than 65 years who were admitted due to COVID-19 and how this has influenced the evolution of patients. DESIGN: This prospective and observational study was performed in patients with COVID-19 infection confirmed by real-time polymerase chain reaction. Data were collected from the first 24 h of admission. All patients admitted during one month to the wards assigned to COVID-19 infection were included. RESULTS: A total of 83 patients were studied. The statistical study of mortality showed associations with age (p = .005), living in a nursing home (p = .022), a high Charlson Comorbidity Index (p = .039), hypertension (p = .032), comorbidities of dementia (p = .019) and cerebral vascular disease (p = .041), and Barthel Index (p = .010). The analysis of the influence of the nutritional state on mortality revealed a statistical association between malnutrition and mortality in the pooled data analysis (p = .005) and analysis by degrees of malnutrition (p = .27). CONCLUSIONS: Malnutrition was a risk factor as powerful as others such as hypertension, age, and different comorbidities. We must evaluate and treat the nutritional status of elderly patients with COVID-19 infection since it directly affects their evolution.

Iron Laboratory Studies in Pediatric Patients With Heart Failure from Dilated Cardiomyopathy.

Iron deficiency (FeD), with or without anemia, in adults with heart failure (HF) is associated with poor outcomes, which can be improved with replacement therapy. A similar therapeutic opportunity may exist for children; however, iron laboratory measurements and FeD have not been described in pediatric patients with HF. A single-center, retrospective study was conducted on 28 patients <21 years old with a diagnosis of dilated cardiomyopathy and HF who had iron laboratories (serum iron, iron saturation, and ferritin) performed. The mean (standard deviation) age at time of laboratory collection was 10.3 (5.5) years. Twenty-seven patients (96.4%) met the criteria for FeD. Serum iron and iron saturation were significantly associated with inpatient hospitalization, being on inotropic medications, or having stage D HF. Low-serum iron was associated with a higher left ventricular end-diastolic dimension and left ventricular end-systolic dimension z-score by echocardiography ((ß -2.58, 95% confidence interval [CI] -4.76, -0.40, p = 0.02) and (ß -2.43, 95% CI -4.70, -0.17, p = 0.04)), respectively. Low ferritin was associated with higher mortality (relative risk 0.29, 95% CI 0.12, 0.70, p = 0.006). In conclusion, FeD was common in this pediatric cohort with more advanced HF. Iron profile abnormalities were associated with worse HF severity and outcomes including mortality.