Seven- and thirty-day mortality in digoxin poisoning: Results from the DIGITOX study.

BACKGROUND: Digoxin poisonings are relatively common and potentially fatal, requiring immediate therapeutic intervention, with special attention to the patient's hemodynamic status and the presence of electrocardiographic and electrolytic disturbances. OBJECTIVE: To identify factors associated with seven-day and thirty-day mortality in digoxin poisoning. DESIGN, SETTINGS AND PARTICIPANTS: A retrospective, observational, multicenter study was conducted across 15 Hospital Emergency Departments (HED) in Spain. All patients over 18 years of age who presented to participating HEDs from 2015 to 2021 were included. The inclusion criteria encompassed individuals meeting the criteria for digoxin poisoning, whether acute or chronic. OUTCOMES MEASURE AND ANALYSIS: To identify independent factors associated with 7-day and 30-day mortality, a multivariate analysis was conducted. This analysis included variables of clinical significance, as well as those exhibiting a trend (p < 0.1) or significance in the bivariate analysis. MAIN FINDINGS: A total of 658 cases of digoxin poisoning were identified. Mortality rates were 4.5% (30 patients) at seven days and 11.1% (73 patients) at thirty days. Regarding 7-day mortality, the mean age of deceased patients was comparable to survivors (84.7 (8.9) vs 83.9 (7.9) years; p = ns). The multivariate analysis revealed that factors independently associated with 7-day mortality encompassed the extent of dependence assessed by the Barthel Index (BI 60-89 OR 0.28; 95% CI 0.10-0.77; p = 0.014 and BI>90 OR 0.22; 95% CI 0.08-0.63; p = 0.005), the identification of ventricular arrhythmias (OR 1.34; 95% CI 1.34-25.21; p = 0.019), and the presence of circulatory (OR 2.84; 95% CI 1.19-6.27; p = 0.019) and neurological manifestations (OR 2.67; 95% CI 1.13-6.27; p = 0.025). Factors independently associated with 30-day mortality encompassed extent of dependence (BI 60-89 OR 0.37; 95% CI 0.20-0.71; p = 0.003 and BI>90 OR 0.18; 95% CI 0.09-0.39; p < 0.001) and the identification of circulatory (OR 2.13; 95% CI 1.10-4.15; p = 0.025) and neurological manifestations (OR 2.39; 95% CI 1.25-3.89; p = 0.006). CONCLUSIONS: The study identifies the degree of dependency assessed by the Barthel Index and the presence of cardiovascular and neurological symptoms as independent predictors of both 7-day and 30-day mortality. Additionally, the detection of ventricular arrhythmia is also an independent factor for 7-day mortality.

Accuracy of International Classification of Diseases Codes for Identifying Acute Optic Neuritis.

BACKGROUND: The accuracy of International Classification of Diseases (ICD) codes for identifying cases of acute optic neuritis (aON) is not known. A prior study reported 61% accuracy for ICD code plus MRI consistent with aON within 2 months. This study determined accuracy for ICD code plus MRI within 2 months regardless of results. METHODS: Retrospective chart review was conducted using a medical record research repository of a tertiary care institution from 1998 to 2019. Subjects with ICD-9/10 codes for ON and an MRI brain and/or orbits within 2 months of earliest (initial) ICD code were included. MRI was classified as positive or negative for aON based on report noting gadolinium-contrast enhancement. Clinical diagnosis at the time of initial code was classified as aON, prior ON, considered ON, alternative diagnosis, or unknown based on review of physician authored clinical notes within 7 days of the initial code. Accuracy of ICD code for aON, acute or prior ON, and acute, prior, or considered ON were calculated for all subjects and stratified based on MRI result. RESULTS: Two hundred fifty-one subjects had MRI results within 2 months of their initial ON ICD code (49 positive MRI [previously reported]; 202 negative MRI). Among those with negative MRI, 32 (16%) had aON, 40 (20%) had prior ON, 19 (9%) considered ON as a diagnosis, 92 (46%) had other confirmed diagnoses, and 19 (9%) had unknown diagnosis at time of code. Considering all subjects, accuracy for ICD code was 25% for acute ON, 41% for acute or prior ON, and 48% for acute, prior, or considered ON. Positive MRI, increased number of ON ICD codes, a code given by an ophthalmologist or neurologist within 2 months, and the presence of a neurology encounter within 2 months were associated with an increased accuracy for clinical aON diagnosis. CONCLUSIONS: In the setting of an MRI within 2 months, ICD codes for ON have low accuracy for acute ON and only slightly better accuracy for acute or prior ON. Accuracy is higher for cases with a positive MRI than those with a negative MRI, suggesting positive MRI in conjunction with ICD codes may help more accurately identify cases. Reliance on ICD and Current Procedural Terminology codes alone to identify aON cases may introduce substantial misclassification bias in claims-based research.

Diagnostic Error in Neuro-ophthalmology: Avenues to Improve.

PURPOSE OF REVIEW: To highlight potential avenues to reduce preventable diagnostic error of neuro-ophthalmic conditions and avoid patient harm. RECENT FINDINGS: Recent prospective studies and studies of patient harm have advanced our understanding. Additionally, recent studies of fundus photography, telemedicine, and artificial intelligence highlight potential avenues for diagnostic improvement. Diagnostic error of neuro-ophthalmic conditions can often be traced to failure to gather an adequate history, perform a complete physical exam, obtain adequate/appropriate neuroimaging, and generate a complete, appropriate differential diagnosis. Improving triage and identification of neuro-ophthalmic conditions by other providers and increasing access to subspecialty neuro-ophthalmology evaluation are essential avenues to reduce diagnostic error. Further research should evaluate the relationship between misdiagnosis and patient harm, and help identify the most impactful potential targets for improvement.

Craniopharyngioma in the Elderly: A Multicenter and Nationwide Study in Spain.

BACKGROUND: Craniopharyngioma (CP) is a rare tumor in the elderly whose clinical features and prognosis are not well known in this population. AIM: To evaluate the clinicopathological features and therapeutic outcomes of CP diagnosed in the elderly. PATIENTS AND METHODS: This was a retrospective, multicenter, national study of CP patients diagnosed over the age of 65 years and surgically treated. RESULTS: From a total of 384 adult CP patients, we selected 53 (13.8%) patients (27 women [50.9%], mean age 72.3 ± 5.1 years [range 65-83 years]) diagnosed after the age of 65 years. The most common clinical symptoms were visual field defects (71.2%) followed by headache (45.3%). The maximum tumor diameter was 2.9 ± 1.1 cm. In most patients, the tumor was suprasellar (96.2%) and mixed (solid-cystic) (58.5%). The surgical approach most commonly used was transcranial surgery (52.8%), and more than half of the patients (54.7%) underwent subtotal resection (STR). Adamantinomatous CP and papillary CP were present in 51 and 45.1%, respectively, with mixed forms in the remaining. Surgery was accompanied by an improvement in visual field defects and in headaches; however, pituitary hormonal hypofunction increased, mainly at the expense of an increase in the prevalence of diabetes insipidus (DI) (from 3.9 to 69.2%). Near-total resection (NTR) was associated with a higher prevalence of DI compared with subtotal resection (87.5 vs. 53.6%, p = 0.008). Patients were followed for 46.7 ± 40.8 months. The mortality rate was 39.6% with a median survival time of 88 (95% CI: 57-118) months. DI at last visit was associated with a lower survival. CONCLUSION: CP diagnosed in the elderly shows a similar distribution by sex and histologic forms than that diagnosed at younger ages. At presentation, visual field alterations and headaches are the main clinical symptoms which improve substantially with surgery. However, surgery, mainly NTR, is accompanied by worsening of pituitary function, especially DI, which seems to be a predictor of mortality in this population.

Factors Associated With Increased Emergency Department Utilization in Patients With Acute Optic Neuritis.

BACKGROUND: Symptoms of acute vision loss and eye pain may lead patients with optic neuritis to seek care in the emergency department (ED). Given the availability of lower cost alternatives for providing medical care for optic neuritis, this study aimed to identify factors associated with higher ED utilization. METHODS: Subjects with acute optic neuritis were identified through a chart review of adults with International Classification of Diseases-9 (ICD-9) or ICD-10 codes for optic neuritis with corresponding gadolinium contrast enhancement of the optic nerve on MRI in the medical record research repository of a tertiary care institution. Subjects were grouped based on the number of ED visits (0-1 and 2-3) within 2 months of either ICD code or MRI. Demographics, characteristics of disease presentation, type and location of medical care, testing (chest imaging, lumbar puncture, optical coherence tomography, spine MRI, visual field, and laboratory tests), treatment, provider specialty of follow-up visits, and duration of care were extracted from the medical record. RESULTS: Of 30 acute optic neuritis subjects (age 41 ± 16 years, range 18-76, 53% [16/30] female), 19 had 0-1 ED visit and 11 had 2-3 ED visits. Most subjects were Caucasian, non-Hispanic (47%), followed by Asian (23%), Hispanic/Latino (17%), Black (10%), and others (3%). Subjects had an initial clinical encounter primarily in the outpatient setting (63%) as compared with the ED (37%). The median time from symptom onset to initial clinical encounter was 4 days with a range of 0-13. Subjects were mostly insured through a private insurance (60%), followed by Medicare/Medicaid (23%) and uninsured (17%). Fewer ED visits were associated with an initial clinical encounter in an outpatient setting (P = 0.02, chi-square), but not residential distance from the hospital or insurance type. Subjects with a higher number of ED visits were more likely to be of Hispanic/Latino ethnicity (P = 0.047, Fisher exact). There was no significant difference in the ophthalmic, radiologic, or laboratory testing performed in both groups. Both groups presented in a similar time frame with similar symptoms and clinical signs. Treatment was similar in both groups. CONCLUSIONS: Subjects with their first clinical encounter for optic neuritis in the ED had more visits to the ED overall when compared with those first seen in an outpatient setting and thus strategies aimed at facilitating outpatient care may help reduce unnecessary ED visits, although some, such as insurance status, may be difficult to modify. Further study in a larger sample is needed to refine these observations.

Trace analysis of UV filters and musks in living fish by in vivo SPME-GC-MS.

A method was developed for the simultaneous determination of two groups of personal care products, namely UV filters (oxybenzone, 3-(4-methylbenzylidene)camphor, padimate-O, 2-ethylhexyl-4-methoxycinnamate, and octocrylene) and polycyclic aromatic musks (galaxolide and tonalide), in fish by in vivo solid-phase microextraction followed by gas chromatography-mass spectrometry. The in vivo method was validated by carrying out in vitro experiments; the method validation parameters were linearity (r2 > 0.98), interday precision (relative standard deviations < 35.50%), limits of detection and quantification ranging from 2 to 25 ng g-1 and 5 to 70 ng g-1, respectively. The calibrations in vivo and in vitro were determined using a pre-equilibrium sampling rate calibration method. In vivo sampling rate (Rs) was greater than that in vitro; therefore in vivo Rs was applied to the uptake and elimination tracing under controlled laboratory conditions to avoid quantitation error. All analytes were bioaccumulated in muscle tissue over the 5-day exposure in different grades depending on their molecular structure and physicochemical properties; the most absorbed compound was tonalide and the least absorbed compound was padimate-O. The elimination rate was initially high with a rapid decrease of the analyte concentrations for the first 24 h; thereafter, the rate of elimination tended to decrease which indicated that the target analytes were bioaccumulated. To our knowledge, this is the first time that UV filters have been analyzed with in vivo SPME-GC-MS. The proposed method is a simple, miniaturized, and non-lethal alternative for the determination of personal care products in living organisms. Graphical abstract.

Altered S-nitrosothiol homeostasis provides a survival advantage to breast cancer cells in HER2 tumors and reduces their sensitivity to trastuzumab.

The monoclonal antibody trastuzumab against HER2/neu, which is overexpressed in 15-20% of breast cancers, has clinical efficacy but many patients do not respond to initial treatment or develop resistance during treatment. Nitric oxide (NO) regulates cell signaling by targeting specific cysteine residues in proteins, forming S-nitrosothiols (SNO) in a process known as S-nitrosylation. We previously reported that molecular characteristics in breast cancer may dictate the tumor response to impaired SNO homeostasis. In the present study, we explored the role of SNO homeostasis in HER2 breast tumors. The antiproliferative action of trastuzumab in HER2-overexpressing BT-474 and SKBR-3 cells was suppressed when S-nitrosoglutathione reductase (GSNOR/ADH5) activity, which plays a key role in SNO homeostasis, was specifically inhibited with the pyrrole derivative compound N6022. Moreover, GSNOR inhibition restored the activation of survival signaling pathways involved in the resistance to anti-HER2 therapies (AKT, Src and c-Abl kinases and TrkA/NRTK1, TrkB/NRTK2, EphA1 and EphA3 receptors) and reduced the apoptotic effect of trastuzumab. Accordingly, GSNOR inhibition augmented the S-nitrosylation of apoptosis-related proteins, including Apaf-1, pSer73/63 c-Jun, calcineurin subunit α and HSF1. In agreement with in vitro data, immunohistochemical analyses of 51 breast tumors showed that HER2 expression was associated with lower expression of GSNOR protein. Moreover, gene expression analysis confirmed that high ADH5/GSNOR gene expression was associated with high patient survival rates in HER2 tumors. In conclusion, our data provide evidence of molecular mechanisms contributing to the progression of HER2+ breast cancers and could facilitate the development of therapeutic options to counteract resistance to anti-HER2 therapies.

Use of diagnostic tests in elderly patients consulting the emergency department. Analysis of the emergency department and elder needs cohort (EDEN-8).

OBJECTIVE: Analyse the association between the use of diagnostic tests and the characteristics of older patients 65 years of age or more who consult the emergency department (ED). METHODS: We performed an analysis of the EDEN cohort that includes patients who consulted 52 Spanish EDs. The association of age, sex, and ageing characteristics with the use of diagnostic tests (blood tests, electrocardiogram (ECG), microbiological cultures, X-ray, computed tomography, ultrasound, invasive techniques) was studied. The association was analysed by calculating the adjusted odds ratios (aOR) and their 95 % confidence intervals (CI) using a logistic regression model. RESULTS: A total of 25,557 patients were analysed. There was an increase in the use of diagnostic tests based on age, with an aOR for blood test of 1.805 (95 %CI 1.671 - 1.950), ECG 1.793 (95 %CI 1.664 - 1.932) and X-ray 1.707 (95 %CI 1.583 - 1.840) in the group of 85 years or more. The use of diagnostic tests is lower in the female population. Most ageing characteristics (cognitive impairment, previous falls, polypharmacy, dependence, and comorbidity) were independently associated with increased use of diagnostic tests. CONCLUSIONS: Age, and the characteristics of ageing itself are generally associated with a greater use of diagnostic tests in the ED.

Use of resources in elderly patients consulting the emergency department: analysis of the Emergency Department and Elder Needs Cohort (EDEN-21).

The elderly population frequently consults the emergency department (ED). This population could have greater use of EDs and hospital health resources. The EDEN cohort of patients aged 65 years or older visiting the ED allowed this association to be investigated. To analyse the association between healthcare resource use and the characteristics of patients over 65 years of age who consult hospital EDs. We performed an analysis of the EDEN cohort, a retrospective, analytical, and multipurpose registry that includes patients over 65 years of age who consulted in 52 Spanish EDs. The impact of age, sex, and characteristics of ageing on the following outcomes was studied: need for hospital admission (primary outcome) and need for observation, stay in the ED > 12 h, prolonged hospital stay > 7 days, need for intensive care unit (ICU) and return to the ED at 30 days related to the index visit (secondary outcomes). The association was analysed by calculating the adjusted odds ratios (aOR) and their 95% confidence intervals (CI), using a logistic regression model. A total of 25,557 patients with a mean age of 78.3 years were analysed, 45% were males. Of note was the presence of comorbidity, a Charlson index ≥ 3 (33%), and polypharmacy (66%). Observation in the ED was required by 26%, 25.4% were admitted to the hospital, and 0.9% were admitted to the ICU. The ED stay was > 12 h in 12.5% and hospital stay > 7 days in 13.5% of cases. There was a progressive increase in healthcare resource use based on age, with an aOR for the need for observation of 2.189 (95% CI 2.038-2.352), ED stay > 12 h 2.136 (95% CI 1.942-2.349) and hospital admission 2.579 (95% CI 2.399-2.772) in the group ≥ 85 years old. Most of the characteristics inherent to ageing (cognitive impairment, falls in the previous 6 months, polypharmacy, functional dependence, and comorbidity) were associated with significant increases in the use of healthcare resources, except for ICU admission, which was less in all the variables studied. Age and the characteristics inherent to ageing are associated with greater use of structural healthcare resources.

Maternal-fetal outcomes of pregnancies in women treated at an inborn errors of metabolism unit.

INTRODUCTION: Intermediate Inborn Errors of Metabolism (IEM) are a group of inherited diseases that include phenylketonuria (PKU), tyrosinemia II (TSII), organic acidaemias and ornithine transcarbamylase deficiency (OTCD), among others. They are increasingly more common in adults due to improved management. This has allowed more affected women to consider having children with good prospects. However, pregnancy may worsen metabolic control and/or increase maternal-fetal complications. The objective is to analyse the characteristics and outcomes of pregnancies of our patients with IEM. METHODS: Retrospective descriptive study. Pregnancies of women with IEM attended to at the adult IEM referral unit of the Hospital Universitario Virgen del Rocío were included. The qualitative variables were described as n(%) and the quantitative as P50 (P25-P75). RESULTS: 24 pregnancies were recorded: 12 newborns were healthy, 1 inherited their mother's disease, 2 had maternal phenylketonuria syndrome, 1 was stillborn (gestational week 31 + 5), 5 were spontaneous abortions and 3 were voluntarily terminated. The gestations were divided into metabolically controlled and uncontrolled. CONCLUSIONS: Pregnancy planning and multidisciplinary management through to postpartum is essential to ensure maternal and fetal health. The basis of treatment in PKU and TSII is a strict protein-limited diet. Events that increase protein catabolism in organic acidaemias and DOTC should be avoided. Further investigation of pregnancy outcomes in women with IEM is needed.

Hyperhomocysteinemia in Adult Patients: A Treatable Metabolic Condition.

Hyperhomocysteinemia (HHcy) is recognized as an independent risk factor for various significant medical conditions, yet controversy persists around its assessment and management. The diagnosis of disorders afffecting homocysteine (Hcy) metabolism faces delays due to insufficient awareness of its clinical presentation and unique biochemical characteristics. In cases of arterial or venous thrombotic vascular events, particularly with other comorbidities, it is crucial to consider moderate to severe HHcy. A nutritional approach to HHcy management involves implementing dietary strategies and targeted supplementation, emphasizing key nutrients like vitamin B6, B12, and folate that are crucial for Hcy conversion. Adequate intake of these vitamins, along with betaine supplementation, supports Hcy remethylation. Lifestyle modifications, such as smoking cessation and regular physical activity, complement the nutritional approach to enhance Hcy metabolism. For individuals with HHcy, maintaining a plasma Hcy concentration below 50 µmol/L consistently is vital to lowering the risk of vascular events. Collaboration with healthcare professionals and dietitians is essential for developing personalized dietary plans addressing the specific needs and underlying health conditions. This integrated approach aims to optimize metabolic processes and reduce the associated health risks.

Evaluating Adherence to Diabetic Retinopathy Care in an Urban Ophthalmology Clinic Utilizing the Compliance With Annual Diabetic Eye Exams Survey.

Introduction The objective of this study was to identify barriers that affect adherence to the management of diabetic retinopathy (DR) in an urban ophthalmology clinic. Patient beliefs regarding diabetic eye care, transportation to the eye clinic, the COVID-19 pandemic, and treatment with panretinal photocoagulation (PRP) or anti-vascular endothelial growth factor (anti-VEGF) injections were investigated. Materials and methods The original Compliance with Annual Diabetic Eye Exams Survey (CADEES) included 44 statements designed with a 5-point Likert scale to assess patients' beliefs and understanding of their eye health and the importance of diabetic eye examinations. This survey was modified to include additional statements regarding the COVID-19 pandemic and free-response questions about transportation barriers and patients' subjective experiences with PRP or anti-VEGF injections. A total of 365 patients with a diagnosis of any stage of DR from SLUCare Ophthalmology were identified as potential participants to complete the telephone survey. Patients were classified as non-adherent if they did not have a dilated eye examination within the past year, missed a scheduled follow-up appointment for DR care within the past year, or missed an appointment for anti-VEGF injections or PRP. The mean Likert scores for each CADEES statement were compared between the adherent and non-adherent groups using independent samples t-tests. Demographics and clinical indicators were also reported and compared between the two groups. Results Out of 365 patients, 68 completed the modified CADEES. Twenty-nine patients were adherent, and 39 patients were non-adherent. Results from six of the 54 CADEES statements were significantly different between the adherent and non-adherent groups. These statements addressed patients' perception of their eye health, self-confidence in making an eye appointment, knowing someone with diabetic eye complications, self-confidence in controlling blood sugar, ability to use public transportation during the COVID-19 pandemic, and prioritizing eye health during the pandemic. There were no significant differences in clinical indicators or demographics between the adherent and non-adherent groups. Of the participants, 39.7% offered reasons for why transportation to the eye clinic was difficult. Patients suggested three novel reasons for missing eye appointments that were not specifically addressed in the CADEES. Fourteen unique barriers were reported for non-adherence with PRP or anti-VEGF injections. Conclusions The CADEES is a thorough tool for evaluating social barriers impacting adherence with DR appointments in an urban ophthalmology clinic. The survey did not identify any clinical or demographic risk factors for non-adherence in this patient population. Decreased patient self-efficacy may lead to non-adherence with the management of DR. The COVID-19 pandemic impacted the adherence of a small percentage of patients.

Characteristics of digoxin toxicity attended in Spanish emergency departments according to type of poisoning and administration of digoxin antibodies: the DIGITOX study. / Características de las intoxicaciones por digoxina atendidas en diversos servicios de urgencias españoles en función del tipo de intoxicación y de la administración de anticuerpos antidigoxina: estudio DIGITOX.

OBJECTIVES: Digoxin toxicity accounts for a small percentage of poisonings attended by emergency departments. This study aimed to describe differences between acute and chronic digoxin toxicity and assess the use of digoxin-specific antibody fragments (digoxin-Fab) as an antidote. MATERIAL AND METHODS: Retrospective, observational, multicenter study in 15 hospital emergency departments in 8 Spanish autonomous communities in 7 years. We collected patient, clinical and treatment variables, and discharge destination. Patients were classified according to whether toxicity was acute or chronic and whether digoxin-Fab was administered or not. RESULTS: Twenty-seven acute and 631 chronic digoxin poisonings were attended. The mean (SD) patient age was 83.9 (7.9) years, and 76.9% were women. Patients with acute toxicity were younger (80.0 [12] years) than those with chronic toxicity (84.1 [7.7] years) (P .038), and accidental poisoning was less common (in 85.2% vs 100% in chronic toxicity; P .001). Cases of acute toxicity were also more serious (Poison Severity Score (29.6% vs 12.5% in chronic toxicity; P .001). Thirty-four patients were treated with digoxin-Fab (5.4%). These patients were younger (78.7 [11.5] years vs 84.2 (7.6) years), their toxicity was more often acute (in 20.6% vs 3.2% in chronic toxicity), more had attempted suicide (8.8% vs 0.2% with chronic toxicity), and more had severe symptoms (50% vs 11.2%) (P .001, all comparisons). Hospital admission was required for 76.1%. Overall, mortality was 11.4%. CONCLUSION: Chronic toxicity accounts for most digoxin poisoning cases, and most patients are women. Acute toxicity is more serious. Patients who required digoxin-Fab have more severe poisoning. Such patients usually have acute toxicity, and attempted suicide is more often the reason for the emergency.

OBJETIVO: Las intoxicaciones por digoxina representan un pequeño porcentaje de las intoxicaciones atendidas en urgencias. El objetivo de este estudio fue describir las diferencias entre intoxicaciones agudas y crónicas y evaluar la administración de su antídoto específico: los anticuerpos antidigoxina (AcAD). METODO: Estudio retrospectivo, observacional y multicéntrico en 15 servicios de urgencias hospitalarios de 8 comunidades autónomas durante 7 años. Se recogieron datos de filiación, clínica, tratamiento y destino al alta. Los pacientes se dividieron según era la intoxicación aguda o crónica y según recibían o no AcAD. RESULTADOS: Se recogieron 27 intoxicaciones agudas y 631 crónicas. La edad media fue de 83,9 (7,9) años, y el 76,9% eran mujeres. Los pacientes con intoxicación aguda tenían menor edad media (80,0 (12) vs 84,1 (7,7) años; p 0,038), y porcentaje de causa accidental (85,2% vs 100%; p 0,001) y mayor gravedad en la escala Poison Severity Score (29,6% vs 12,5%; p 0,001). Treinta y cuatro pacientes recibieron AcAD (5,4%) y constituyen un grupo de menor edad [78,7 (11,5) vs 84,2 (7,6); p 0,001], con mayor porcentaje de intoxicaciones agudas (20,6% vs 3,2%), intencionalidad suicida (8,8% vs 0,2%) y gravedad (50% vs 11,2%, p 0,001 en todas las comparaciones). El 76,1% precisó ingreso. La mortalidad fue del 11,4%. CONCLUSIONES: Las intoxicaciones por digoxina suelen ser crónicas y predominan en mujeres. Las intoxicaciones agudas son de mayor gravedad. Los pacientes que precisaron administración de AcAD tenían intoxicaciones más graves y mayor porcentaje de intoxicaciones agudas y con intencionalidad suicida.

Maintenance of S-nitrosothiol homeostasis plays an important role in growth suppression of estrogen receptor-positive breast tumors.

INTRODUCTION: Protein denitrosylation by thioredoxin reductase (TrxR) is key for maintaining S-nitrosothiol (SNO) homeostasis, although its role in tumor progression is unknown. Therefore, the present study aimed to assess the role of altered SNO homeostasis in breast cancer cells. METHODS: The impairment of SNO homeostasis in breast cancer cells was achieved with the highly specific TrxR inhibitor auranofin and/or exposure to S-nitroso-L-cysteine. S-nitrosylated proteins were detected using the biotin switch assay. Estrogen receptor (ER) alpha knockdown was achieved using RNA silencing technologies and subcellular localization of ERα was analyzed by confocal microscopy. The Oncomine database was explored for TrxR1 (TXNRD1) expression in breast tumors and TrxR1, ER and p53 expression was analyzed by immunohistochemistry in a panel of breast tumors. RESULTS: The impairment of SNO homeostasis enhanced cell proliferation and survival of ER+ MCF-7 cells, but not of MDA-MB-231 (ER-, mut p53) or BT-474 (ER+, mut p53) cells. This enhanced cell growth and survival was associated with Akt, Erk1/2 phosphorylation, and augmented cyclin D1 expression and was abolished by the ER antagonist fulvestrant or the p53 specific inhibitor pifithrin-α. The specific silencing of ERα expression in MCF-7 cells also abrogated the growth effect of TrxR inhibition. Estrogenic deprivation in MCF-7 cells potentiated the pro-proliferative effect of impaired SNO homeostasis. Moreover, the subcellular distribution of ERα was altered, with a predominant nuclear localization associated with phosphorylation at Thr311 in those cells with impaired SNO homeostasis. The impairment of SNO homeostasis also expanded a cancer stem cell-like subpopulation in MCF-7 cells, as indicated by the increase of percentage of CD44+ cells and the augmented capability to form mammospheres in vitro. Notably, ER+ status in breast tumors was significantly associated with lower TXNDR1 mRNA expression and immunohistochemical studies confirmed this association, particularly when p53 abnormalities were absent. CONCLUSION: The ER status in breast cancer may dictate tumor response to different nitrosative environments. Impairment of SNO homeostasis confers survival advantages to ER+ breast tumors, and these molecular mechanisms may also participate in the development of resistance against hormonal therapies that arise in this type of mammary tumors.

Predictors of revisits within 1 year by patients after acute COVID-19: the HUBCOVID365 cohort study. / Predictores de revisita en pacientes con infección aguda COVID-19 con seguimiento al año: estudio de cohorte HUBCOVID365.

OBJECTIVES: To analyze the frequencies of 3 types of hospital revisits by patients after treatment for COVID-19 in the emergency department. MATERIAL AND METHODS: Retrospective observational study of consecutive patients who came to the emergency department in March and April 2020 and were discharged alive with a diagnosis of COVID-19. Baseline and acute episode data were collected and the patients were followed for 1 year. We analyzed variables associated with revisits for any reason, revisits related to COVID-19, and early COVID-19-related revisits (within 30 days). RESULTS: A total of 1352 patients with a mean age of 62.1 years (52.9% male) were studied. A total of 553 revisits were made by 342 patients (25.3%) for any reason; 132 (9.8%) revisited in relation to COVID-19 at least once. Of those, 103 (7.6%) revisited within 30 days (early) and 29 (2.2%) came later. COVID-19-related revisits were associated with thrombotic events (odds ratio [OR], 7.58; 95% CI, 1.75-32.81) and pulmonary fibrosis (OR, 4.95; 95% CI, 1.27-19.24); early revisits were inversely associated with follow-up management by a contracted health care support service (OR, 0.18; 95% CI, 0.03-0.92). Hospital admission during the initial visit was significantly associated with fewer revisits for any reason or related to COVID-19 at any time. CONCLUSION: Fewer than half the total number of emergency department revisits after initial care for COVID-19 were related to the novel coronavirus infection. Revisits occurred more often in the first 30 days after discharge. Later COVID-19-related revisits were uncommon, but given the large number of patients with this infection, such visits can be expected.

OBJETIVO: Analizar diferentes categorías de revisita (RV) al año en pacientes con infección COVID-19 que consultan en un servicio de urgencias hospitalario (SUH). METODO: Estudio observacional, retrospectivo, que incluyó pacientes consecutivos que consultaron al SUH en los meses de marzo y abril de 2020 con diagnóstico de COVID-19 y fueron dados de alta vivos del hospital. Se recogieron variables basales y del episodio agudo y se realizó un seguimiento al año. Se hicieron tres comparaciones identificando variables asociadas a la RV total, RV relacionada con COVID-19 (RCovid) y RCovid precoz (# 30 días). RESULTADOS: Se analizaron 1.352 pacientes con edad media de 62,1 años y 52,9% varones. En el seguimiento al año hubo 553 RV en 342 (25,3%) pacientes, 132 (9,8%) con al menos una RCovid, 103 (7,6%) precoz y 29 (2,2%) tardía. La RCovid se relacionó con la presencia de fenómenos trombóticos [OR 7,58 (IC 95%: 1,75-32,81)] y la fibrosis pulmonar [OR 4,95 (IC 95%: 1,27-19,24)]; y la RCovid precoz se relacionó inversamente con alta a dispositivo de soporte sanitario [OR 0,18 (IC 95%: 0,03-0,92)]. El ingreso hospitalario en el evento índice disminuyó la RV total y RCovid y las hospitalizaciones derivadas de esta RV de manera significativa a largo plazo. CONCLUSIONES: Menos de la mitad de la RV total tras una infección COVID-19 está relacionada con la infección, y es más frecuente en los primeros 30 días. La RCovid tardía no es frecuente, pero dado el elevado número de pacientes que han sido infectados por COVID-19 se debe tener en cuenta.

Postoperative water and electrolyte disturbances after extended endoscopic endonasal transsphenoidal surgery.

Introduction: Water and electrolyte disturbances are common after pituitary surgery and can generally be classified into transient hypotonic polyuria and transient or permanent diabetes insipidus (DI). The prevalence varies in the literature between 31-51% for transient hypotonic polyuria, 5.1-25.2% for transient DI, and 1-8.8% for permanent DI. Objective: The aim of this study was to identify the prevalence of water and electrolyte disturbances with polyuria and the preoperative and postoperative predictive factors in patients undergoing surgery with an extended endoscopic endonasal approach. Material and methods: This retrospective observational descriptive study included 203 patients with a diagnosis of pituitary adenoma who underwent their first transsphenoidal surgery via the extended endoscopic endonasal approach between April 2013 and February 2020. The diagnosis of water and electrolyte disturbances was based on the criterion for polyuria (>4 ml/kg/h). Postoperative polyuria was defined as those cases diagnosed during the immediate postsurgical period that resolved prior to discharge. Transient DI included all cases with a duration of less than 6 months but still present at hospital discharge, and permanent DI included cases lasting more than 6 months. Results: The overall prevalence of water and electrolyte disorders was 30.5% (62), and the prevalence of postoperative polyuria was 23.6% (48). The median number of desmopressin doses administered to patients with postoperative polyuria was one dose (interquartile range [IQR] 1-2), and thus the median duration of treatment was 0 days. The median initiation of desmopressin was the second day after surgery (IQR 1-2). The overall prevalence of DI was 6.89%. Among the patients with transient DI, the duration was less than 3 months in three patients (1.47%), and between 3 and 6 months in two (0.98%). Nine patients had permanent DI (4.43%). (4.43%). Conclusions: The prevalence of electrolyte disturbances in our study was high, although similar to that found in the literature. Most of the cases were transient hypotonic polyuria that resolved within one day. The prevalence of transient DI in our cohort was lower than that described in the literature, while permanent DI was similar.

How the COVID-19 pandemic has affected the training of Endocrinology and Nutrition Residents. Results of a survey by the Spanish Society of Endocrinology and Nutrition.

INTRODUCTION: COVID-19 disease has become a priority for our healthcare system. The resident physicians training in endocrinology and nutrition (E&N residents) have been integrated into the COVID-19 teams. This study has been designed with the aim of analysing the educational, occupational and health impact on E&N residents. MATERIAL AND METHODS: Cross-sectional observational study via a web survey, aimed at E&N residents who are members of the SEEN, carried out in November 2020. The following data were analysed: demographic variables, number of beds in the training hospital, alteration of rotations, integration in COVID-19 teams, participation in telemedicine, scientific activity and impact on physical and emotional health. RESULTS: 87 responses were obtained (27% of all E&N residents), 67.8% women, 28.1 ±â€¯1.8 years, 60% 4th year E&N residents. 84% participated in COVID-19 teams and 93% in the telemedicine consultations of their service. Most have had their rotations interrupted. 97.7% have participated in scientific meetings or virtual congresses and a third of them have collaborated in scientific work on COVID-19 in relation to endocrinology and nutrition. Overall, 75.8% think the pandemic has affected their mood a lot or quite a lot, and 73.8% think that the pandemic has negatively impacted their training. CONCLUSIONS: The SARS-CoV-2 pandemic has compromised the training, work activity and health of E&N residents. They have been integrated both in COVID-19 teams and in the restructured activity of their departments. However, they have managed to continue their training in virtual format and have participated in scientific work.

Cardiometabolic and Nutritional Morbidities of a Large, Adult, PKU Cohort from Andalusia.

The establishment of national neonatal screening systems has resulted in improved quality of life and life expectancy in patients with phenylketonuria (PKU). This has led to the development of multidisciplinary treatment units for adult patients with PKU. We present a retrospective descriptive study of a cohort of 90 adult patients (>16 years) with PKU under active follow-up in two reference centers in Andalusia. We analyzed disease severity, treatment type, demographic variables, cardiovascular risk factors, vitamin and hormone profiles, and bone metabolism. The median (interquartile range)age was 29 (23−38) years, 47 (52.2%) were women and 43 (47.8%) were men. Eighty (88.9%) had classical PKU, five (5.6%) moderate PKU, and five (5.6%) mild PKU. Diagnosis was by neonatal screening in 62 (68.9%) of the patients. The rest had late diagnosis. Treatment with sapropterin was given to 18 (20%) patients and diet and nutrition therapy to 72 (80%). There was adequate metabolic control according to Phe levels in 43 (47.78%) patients. Body mass index was 26.61 (22.7−31.1) kg/m2. Twenty-six (29.2%) patients had obesity, 7 (7.9%) hypertension, 2 (2.2%) type 2 diabetes, 26 (28.89%) dyslipidemia, 14 (15.6%) elevated total cholesterol, 9 (15.8%) decreased high-density lipoprotein cholesterol and 16 (17.8%) hypertriglyceridemia. Seven (10.3%) patients had osteoporosis and 28 (41.17%) osteopenia. Twenty-six (30.6%) had vitamin D (25OH) deficiency and four (4.5%) vitamin B12 deficiency. Although we observed no differences with most vascular risk factors, we found a high prevalence of obesity in relation to the age of the cohort. A continued evaluation of comorbidities in these patients is therefore needed, despite adequate metabolic control.

[How the COVID-19 pandemic has affected the training of Endocrinology and Nutrition Residents. Results of a survey by the Spanish Society of Endocrinology and Nutrition]. / Cómo ha afectado la pandemia COVID-19 en la formación de los MIR de Endocrinología y Nutrición. Resultados de una encuesta de la Sociedad Española de Endocrinología y Nutrición.

INTRODUCTION: COVID-19 disease has become a priority for our healthcare system. The resident physicians training in endocrinology and nutrition (E&N residents) have been integrated into the COVID-19 teams. This study has been designed with the aim of analysing the educational, occupational and health impact on E&N residents. MATERIAL AND METHODS: Cross-sectional observational study via a web survey, aimed at E&N residents who are members of the SEEN, carried out in November 2020. The following data were analysed: demographic variables, number of beds in the training hospital, alteration of rotations, integration in COVID-19 teams, participation in telemedicine, scientific activity and impact on physical and emotional health. RESULTS: 87 responses were obtained (27% of all E&N residents), 67.8% women, 28.1 ± 1.8 years, 60% 4th year E&N residents. 84% participated in COVID-19 teams and 93% in the telemedicine consultations of their service. Most have had their rotations interrupted. 97.7% have participated in scientific meetings or virtual congresses and a third of them have collaborated in scientific work on COVID-19 in relation to endocrinology and nutrition. Overall, 75.8% think the pandemic has affected their mood a lot or quite a lot, and 73.8% think that the pandemic has negatively impacted their training. CONCLUSIONS: The SARS-CoV-2 pandemic has compromised the training, work activity and health of E&N residents. They have been integrated both in COVID-19 teams and in the restructured activity of their departments. However, they have managed to continue their training in virtual format and have participated in scientific work.

Poisoning cases in Catalonia: characteristics according to age groups in the Intox.28 study. / Características de las intoxicaciones agudas atendidas en Cataluña y diferencias según grupos de edad: Estudio Intox-28.

OBJECTIVES: The Toxicology Working Group of the Catalan Society of Emergency Medicine (SoCMUETox) began the Intox-28 study in 2013. The aim was to identify differences in poisoning cases between 3 age groups. MATERIAL AND METHODS: Descriptive observational study of poisoning cases managed in 8 hospital emergency departments on the 28th day of each month from 2013 to 2019. We gathered information on patient particulars, type of poison, clinical data, and discharge destination. The patient sample was distributed into 3 groups for comparison: minors under the age of 17 years, adults aged 17 to 65 years, and adults over the age of 65 years. RESULTS: The hospitals registered 1088 cases: 132, 859, and 97 in each age group. In comparisons between the minors and the adults aged 65 years or younger, the minors had more females (58.3% vs 46.1%), fewer recreational poisonings (22% vs 46.1%) more poisonings inside the home (67.4% vs 51.1%), more medication poisonings (49.2% vs 31.1%), and less often received treatment (43.2% vs 73%) (P .001, all comparisons). The proportion of older adults receiving treatment (73.2%) was similar to that of the younger adults. CONCLUSION: The characteristics of poisonings vary according to age. Differences lie in gender, intentionality, and type of poison.

OBJETIVO: El Grupo de Trabajo de Toxicología de la Societat Catalana de Medicina d'Urgències i Emergències (SoCMUETox) inició en 2013 el estudio Intox-28. El objetivo de este trabajo es evaluar las diferencias existentes en las características de las intoxicaciones según la edad de los pacientes. METODO: Estudio descriptivo observacional de las intoxicaciones atendidas en 8 servicios de urgencias hospitalarios (SUH) el día 28 de cada mes durante el periodo 2013-19. Se recogieron datos demográficos, tipo de tóxico, datos clínicos y destino al alta. Los pacientes se dividieron en 3 grupos: menores de 17 años, adultos (entre 17 y 65 años) y mayores de 65 años. RESULTADOS: Se registraron 1.088 intoxicaciones: 132 (12,1%), 859 (78,9%) y 97 (8,9%) en cada grupo de edad respectivamente. En comparación a los pacientes adultos, en los menores de 17 años hubo más mujeres (58,3% vs 46,1%; p 0,001), menos intoxicaciones de tipo recreativo (22% vs 46,1%; p 0,001) y acontecieron más frecuentemente en el domicilio (67,4% vs 51,1%; p 0,001). El tipo de tóxico más implicado fueron los fármacos (49,2% vs 31,1%; p 0,001) y precisaron tratamiento con menor frecuencia (43,2% vs 73%; p 0,001). Los mayores de 65 años precisaron tratamiento en porcentaje similar a los pacientes de 17 a 65 años (73,2%). CONCLUSIONES: Existen diferencias entre los grupos de edad, entre las que destacan el sexo predominante, la intencionalidad de la intoxicación y el tipo de tóxico implicado.