Near-pair patch generative adversarial network for data augmentation of focal pathology object detection models.

Purpose: The limited volume of medical training data remains one of the leading challenges for machine learning for diagnostic applications. Object detectors that identify and localize pathologies require training with a large volume of labeled images, which are often expensive and time-consuming to curate. To reduce this challenge, we present a method to support distant supervision of object detectors through generation of synthetic pathology-present labeled images. Approach: Our method employs the previously proposed cyclic generative adversarial network (cycleGAN) with two key innovations: (1) use of "near-pair" pathology-present regions and pathology-absent regions from similar locations in the same subject for training and (2) the addition of a realism metric (Fréchet inception distance) to the generator loss term. We trained and tested this method with 2800 fracture-present and 2800 fracture-absent image patches from 704 unique pediatric chest radiographs. The trained model was then used to generate synthetic pathology-present images with exact knowledge of location (labels) of the pathology. These synthetic images provided an augmented training set for an object detector. Results: In an observer study, four pediatric radiologists used a five-point Likert scale indicating the likelihood of a real fracture (1 = definitely not a fracture and 5 = definitely a fracture) to grade a set of real fracture-absent, real fracture-present, and synthetic fracture-present images. The real fracture-absent images scored 1.7±1.0, real fracture-present images 4.1±1.2, and synthetic fracture-present images 2.5±1.2. An object detector model (YOLOv5) trained on a mix of 500 real and 500 synthetic radiographs performed with a recall of 0.57±0.05 and an F2 score of 0.59±0.05. In comparison, when trained on only 500 real radiographs, the recall and F2 score were 0.49±0.06 and 0.53±0.06, respectively. Conclusions: Our proposed method generates visually realistic pathology and that provided improved object detector performance for the task of rib fracture detection.

PAI-1 Regulates the Cytoskeleton and Intrinsic Stiffness of Vascular Smooth Muscle Cells.

BACKGROUND: Plasma concentration of PAI-1 (plasminogen activator inhibitor-1) correlates with arterial stiffness. Vascular smooth muscle cells (SMCs) express PAI-1, and the intrinsic stiffness of SMCs is a major determinant of total arterial stiffness. We hypothesized that PAI-1 promotes SMC stiffness by regulating the cytoskeleton and that pharmacological inhibition of PAI-1 decreases SMC and aortic stiffness. METHODS: PAI-039, a specific inhibitor of PAI-1, and small interfering RNA were used to inhibit PAI-1 expression in cultured human SMCs. Effects of PAI-1 inhibition on SMC stiffness, F-actin (filamentous actin) content, and cytoskeleton-modulating enzymes were assessed. WT (wild-type) and PAI-1-deficient murine SMCs were used to determine PAI-039 specificity. RNA sequencing was performed to determine the effects of PAI-039 on SMC gene expression. In vivo effects of PAI-039 were assessed by aortic pulse wave velocity. RESULTS: PAI-039 significantly reduced intrinsic stiffness of human SMCs, which was accompanied by a significant decrease in cytoplasmic F-actin content. PAI-1 gene knockdown also decreased cytoplasmic F-actin. PAI-1 inhibition significantly increased the activity of cofilin, an F-actin depolymerase, in WT murine SMCs, but not in PAI-1-deficient SMCs. RNA-sequencing analysis suggested that PAI-039 upregulates AMPK (AMP-activated protein kinase) signaling in SMCs, which was confirmed by Western blotting. Inhibition of AMPK prevented activation of cofilin by PAI-039. In mice, PAI-039 significantly decreased aortic stiffness and tunica media F-actin content without altering the elastin or collagen content. CONCLUSIONS: PAI-039 decreases intrinsic SMC stiffness and cytoplasmic stress fiber content. These effects are mediated by AMPK-dependent activation of cofilin. PAI-039 also decreases aortic stiffness in vivo. These findings suggest that PAI-1 is an important regulator of the SMC cytoskeleton and that pharmacological inhibition of PAI-1 has the potential to prevent and treat cardiovascular diseases involving arterial stiffening.

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.

A synchronized, large-scale field experiment using Arabidopsis thaliana reveals the significance of the UV-B photoreceptor UVR8 under natural conditions.

This study determines the functional role of the plant ultraviolet-B radiation (UV-B) photoreceptor, UV RESISTANCE LOCUS 8 (UVR8) under natural conditions using a large-scale 'synchronized-genetic-perturbation-field-experiment'. Laboratory experiments have demonstrated a role for UVR8 in UV-B responses but do not reflect the complexity of outdoor conditions where 'genotype × environment' interactions can mask laboratory-observed responses. Arabidopsis thaliana knockout mutant, uvr8-7, and the corresponding Wassilewskija wild type, were sown outdoors on the same date at 21 locations across Europe, ranging from 39°N to 67°N latitude. Growth and climatic data were monitored until bolting. At the onset of bolting, rosette size, dry weight, and phenolics and glucosinolates were quantified. The uvr8-7 mutant developed a larger rosette and contained less kaempferol glycosides, quercetin glycosides and hydroxycinnamic acid derivatives than the wild type across all locations, demonstrating a role for UVR8 under field conditions. UV effects on rosette size and kaempferol glycoside content were UVR8 dependent, but independent of latitude. In contrast, differences between wild type and uvr8-7 in total quercetin glycosides, and the quercetin-to-kaempferol ratio decreased with increasing latitude, that is, a more variable UV response. Thus, the large-scale synchronized approach applied demonstrates a location-dependent functional role of UVR8 under natural conditions.

Bifocal diffractive lenses based on the aperiodic Kolakoski sequence.

In this work, we present a new family of Zone Plates (ZPs) designed using the self-generating Kolakoski sequence. The focusing and imaging properties of these aperiodic diffractive lenses coined Kolakoski Zone Plates (KZPs) are extensively studied. It is shown that under monochromatic plane-wave illumination, a KZP produces two main foci of the same intensity along the axial axis. Moreover, one of the corresponding focal lengths is double the other, property correlated with the involved aperiodic sequence. This distinctive optical characteristic is experimentally confirmed. We have also obtained the first images provided by these bifocal new diffractive lenses.

Granulocyte and monocyte adsorptive apheresis (GMA) in patients with inflammatory bowel disease: A useful therapeutic tool not just in ulcerative colitis but also in Crohn's disease.

INTRODUCTION: Granulocyte and monocyte adsorptive apheresis (GMA) removes neutrophils and monocytes from peripheral blood, preventing their incorporation into the inflamed tissue also influencing cytokine balance. Published therapeutic efficacy in ulcerative colitis (UC) is more consistent than in Crohn's disease (CD). We assessed clinical efficacy of GMA in UC and CD 4 weeks after last induction session, at 3 and 12 months, sustained remission and corticosteroid-free remission. PATIENTS AND METHOD: Retrospective observational study of UC and CD patients treated with GMA. Partial Disease Activity Index-DAIp in UC and Harvey-Bradshaw Index-HBI in CD assessed efficacy of Adacolumn® with induction and optional maintenance sessions. RESULTS: We treated 87 patients (CD-25, UC-62), 87.3% corticosteroid-dependent (CSD), 42.5% refractory/intolerant to immunomodulators. In UC, remission and response were 32.2% and 19.3% after induction, 35.5% and 6.5% at 12 weeks and 29% and 6.5% at 52 weeks. In CD, remission rates were 60%, 52% and 40% respectively. In corticosteroid-dependent and refractory or intolerant to INM patients (UC-41, CD-14), 68.3% of UC achieved remission or response after induction, 51.2% at 12 weeks and 46.3% at 52 weeks, and 62.3%, 64.3% and 42.9% in CD. Maintained remission was achieved by 66.6% in CD and 53.1% in UC. Up to 74.5% of patients required corticosteroids at some timepoint. Corticosteroid-free response/remission was 17.7% in UC and 24% in CD. CONCLUSIONS: GMA is a good therapeutic tool for both in UC and CD patients. In corticosteroid-dependent and refractory or intolerant to INM patients it avoids biological therapy or surgery in up to 40% of them in one year.

Withdrawal of drug therapy in responders to cardiac resynchronization therapy: rationale and design of the REMOVE trial.

INTRODUCTION AND OBJECTIVES: Cardiac resynchronization therapy (CRT) is an effective treatment for patients with nonischemic dilated cardiomyopathy associated with left bundle branch block (LBBB). In these patients, the device can normalize left ventricular ejection fraction (LVEF). Nevertheless, it remains unclear whether CRT responders still require neurohormonal blockers. The aim of this study is to determine the long-term safety of withdrawing drug therapy in these patients. METHODS: The REMOVE trial is a prospective, multicenter, open-label and randomized 1:1 study designed to assess the effect of withdrawing neurohormonal blockers in patients with nonischemic dilated cardiomyopathy associated with left bundle branch block who recovered LVEF after CRT. The study will include a 12-month follow-up with the option to continue into the follow-up extension phase for up to 24 months. The primary endpoint is the recurrence of cardiomyopathy defined as any of the following criteria: a) a reduction in LVEF >10% (provided the LVEF is <50%); b) a reduction in LVEF >10% accompanied by an increase >15% in the indexed end-systolic volume relative to the previous value and in a range higher than the normal values, or c) decompensated heart failure requiring intravenous diuretic administration. In patients meeting the primary endpoint, drug therapy will be restarted. CONCLUSIONS: The results of this study will help to enhance our understanding of CRT superresponders, a specific group of patients. Registred at ClinicalTrials.gov (Identifier: NCT05151861).

Small angle scattering reveals the orientation of cytochrome P450 19A1 in lipoprotein nanodiscs.

Human aromatase (CYP19A1), the cytochrome P450 enzyme responsible for conversion of androgens to estrogens, was incorporated into lipoprotein nanodiscs (NDs) and interrogated by small angle X-ray and neutron scattering (SAXS/SANS). CYP19A1 was associated with the surface and centered at the edge of the long axis of the ND membrane. In the absence of the N-terminal anchor, the amphipathic A'- and G'-helices were predominately buried in the lipid head groups, with the possibly that their hydrophobic side chains protrude into the hydrophobic, aliphatic tails. The prediction is like that for CYP3A4 based on SAXS employing a similar modeling approach. The orientation of CYP19A1 in a ND is consistent with our previous predictions based on molecular dynamics simulations and lends additional credibility to the notion that CYP19A1 captures substrates from the membrane.

N-terminal pro-B-type natriuretic peptide post-discharge monitoring in the management of patients with heart failure and preserved ejection fraction - a randomized trial: The NICE study.

AIMS: There is a lack of specific studies assessing the impact of natriuretic peptide monitoring in the post-discharge management of patients with heart failure (HF) and preserved ejection fraction (HFpEF), throughout the vulnerable phase following acute HF hospitalization. The NICE study aims to assess the clinical benefit of incorporating N-terminal pro-B-type natriuretic peptide (NT-proBNP) into the post-discharge management of HFpEF patients. METHODS AND RESULTS: Individuals admitted with HFpEF (left ventricular ejection fraction >50%) were included in a multicentre randomized controlled study employing an open-label design with event blinding (NCT02807168). Upon discharge, 157 patients were randomly allocated to either NT-proBNP monitoring (n = 79) or no access to NT-proBNP (control group, n = 78) during pre-scheduled visits at 2, 4 and 12 weeks. Clinical endpoints were evaluated at 6 months. The primary endpoint of HF rehospitalizations occurred in 12.1% patients, without significant differences observed between the NT-proBNP monitoring group (12.8%) and the control group (11.4%) (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.47-2.81, p = 0.760). Regarding secondary endpoints, the NT-proBNP monitoring group demonstrated a significantly lower risk of death (1.3% vs. 10.1%; HR 0.12, 95% CI 0.02-0.98; p = 0.048), whereas non-HF hospitalizations (12.8% vs. 19.0%, p = 0.171) and any adverse clinical event (26.9% vs. 36.7%, p = 0.17) did not reach statistical significance [Correction added on 29 April 2024, after first online publication: In the preceding sentence, "95% CI 0.02 - 0.09" has been corrected to "95% CI 0.02 - 0.98; p = 0.048" in this version.]. Awareness of NT-proBNP levels were associated with higher doses of diuretics and renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers) in the NT-proBNP monitoring group. CONCLUSIONS: Post-discharge monitoring of NT-proBNP in HFpEF patients did not exhibit an association with reduced rates of HF hospitalization in this study. Nonetheless, it appears to enhance global clinical management by optimizing medical therapies and contributing to improved overall survival.

Levosimendán ambulatorio repetitivo como puente al trasplante cardiaco / Repetitive ambulatory levosimendan as a bridge to heart transplantation

Introducción y objetivos:El levosimendán ambulatorio repetitivo es una opción como puente al trasplante cardiaco (TxC), aunque la evidencia sobre su eficacia y su seguridad es escasa. El objetivo del registro LEVO-T es describir a los pacientes en lista de TxC que reciben levosimendán, sus pautas y los eventos clínicos durante el seguimiento, en comparación con los que no lo reciben. Métodos: Se revisó en retrospectiva a los pacientes en lista de espera para TxC electivo de 14 centros españoles desde 2015 hasta 2020. Resultados: Se incluyó a 1.015 pacientes consecutivos; los 238 (23,4%) que recibieron levosimendán mostraron más ingresos por insuficiencia cardiaca (IC) el año anterior y peor perfil clínico. Las dosis fijas por necesidades clínicas fueron la pauta más frecuente. Dos pacientes (0,8%) presentaron arritmias ventriculares no mortales. No hubo diferencias en hospitalizaciones por IC entre los que comenzaron levosimendán en los primeros 30 días después de inclusión y los que no (el 33,6 frente al 34,5%; p=0,848). De estos últimos, 102 (32,9%) pasaron a levosimendán después de un ingreso por IC, y la tasa de ingresos por IC/mes varió de 0,57 antes del levosimendán a 0,21 después. El análisis mediante emparejamiento por puntuación de propensión no mostró diferencias entre los pacientes con y sin levosimendán en la supervivencia a 1 año tras la inclusión en lista (HR=1,03; IC95%, 0,36-2,97; p=0,958) ni en la supervivencia tras el TxC (HR=0,97; IC95%, 0,60-1,56; p=0,958). Conclusiones: El levosimendán ambulatorio repetitivo como puente al trasplante cardiaco es un tratamiento frecuente y seguro que podría reducir ingresos por IC. (AU)

Introduction and objectives: Repetitive ambulatory doses of levosimendan are an option as a bridge to heart transplantation (HT), but evidence regarding the safety and efficacy of this treatment is scarce. The objective of the LEVO-T Registry is to describe the profile of patients on the HT list receiving levosimendan, prescription patterns, and clinical outcomes compared with patients not on levosimendan. Methods: We retrospectively reviewed all patients listed for elective HT from 2015 to 2020 from 14 centers in Spain. Results: A total of 1015 consecutive patients were included, of whom 238 patients (23.4%) received levosimendan. Patients treated with levosimendan had more heart failure (HF) admissions in the previous year and a worse clinical profile. The most frequent prescription pattern were fixed doses triggered by the patients’ clinical needs. Nonfatal ventricular arrhythmias occurred in 2 patients (0.8%). No differences in HF hospitalizations were found between patients who started levosimendan in the first 30 days after listing and those who did not (33.6% vs 34.5%; P=.848). Among those who did not, 102 patients (32.9%) crossed over to levosimendan after an HF admission. These patients had a rate of 0.57 HF admissions per month before starting levosimendan and 0.21 afterwards. Propensity score matching analysis showed no differences in survival at 1 year after listing between patients receiving levosimendan and those who did not (HR, 1.03; 95%CI, 0.36-2.97; P=.958) or in survival after HT (HR, 0.97; 95%CI, 0.60-1.56; P=.958). Conclusions: Repetitive levosimendan in an ambulatory setting as a bridge to heart transplantation is commonly used, is safe, and may reduce HF hospitalizations. (AU)

An Acute Infection due to Hepatitis E in the Context of a Patient with Rituximab and Methotrexate Therapy.

Background: This report presents the influence of immunosuppression by new rheumatological therapies on hepatitis E virus infection in a 54-year-old male patient with an anti-synthetase syndrome and treatment with methotrexate and rituximab. Case description: The patient arrived at the Emergency Department with epigastric pain, vomiting and dark urine. Initial examination revealed signs of inflammation and hepatic dysfunction. Subsequent laboratory tests and imaging confirmed acute hepatitis E infection in the context of recent initiation of rituximab therapy. Despite initial suspicion of pancreatitis, subsequent investigations ruled out pancreatic involvement. Treatment with ribavirin, along with supportive measures, led to significant clinical improvement with resolution of jaundice, ascites, and oedema. Conclusions: This case underscores the importance of considering hepatitis E in patients with autoimmune conditions, especially when initiating immunosuppressive therapies, a situation that is not well described in scientific literature and is increasingly common, necessitating proper recognition. LEARNING POINTS: Suspect hepatitis E virus infection in the presence of persistent liver failure of unknown cause.Recognise immunosuppression as a cause of increased risk of hepatitis E infection.Take into account the repercussions of immunosuppressive therapy such as rituximab regarding hepatitis E infections in immunocompromised patients.

High sensitivity methods for automated rib fracture detection in pediatric radiographs.

Rib fractures are highly predictive of non-accidental trauma in children under 3 years old. Rib fracture detection in pediatric radiographs is challenging because fractures can be obliquely oriented to the imaging detector, obfuscated by other structures, incomplete, and non-displaced. Prior studies have shown up to two-thirds of rib fractures may be missed during initial interpretation. In this paper, we implemented methods for improving the sensitivity (i.e. recall) performance for detecting and localizing rib fractures in pediatric chest radiographs to help augment performance of radiology interpretation. These methods adapted two convolutional neural network (CNN) architectures, RetinaNet and YOLOv5, and our previously proposed decision scheme, "avalanche decision", that dynamically reduces the acceptance threshold for proposed regions in each image. Additionally, we present contributions of using multiple image pre-processing and model ensembling techniques. Using a custom dataset of 1109 pediatric chest radiographs manually labeled by seven pediatric radiologists, we performed 10-fold cross-validation and reported detection performance using several metrics, including F2 score which summarizes precision and recall for high-sensitivity tasks. Our best performing model used three ensembled YOLOv5 models with varied input processing and an avalanche decision scheme, achieving an F2 score of 0.725 ± 0.012. Expert inter-reader performance yielded an F2 score of 0.732. Results demonstrate that our combination of sensitivity-driving methods provides object detector performance approaching the capabilities of expert human readers, suggesting that these methods may provide a viable approach to identify all rib fractures.

Complete remission with histamine blocker in a patient with intractable hyperadrenergic postural orthostatic tachycardia syndrome secondary to long coronavirus disease syndrome.

The COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has emerged as a global public health concern and its sequels have barely started to outcrop. A good percentage of patients who suffered from COVID-19 are prone to develop long-COVID or post-COVID condition (PCC), a multisystemic, heterogeneous, chronic disorder. Patients with PCC may experience diverse manifestations, of which cardiovascular and neurological symptoms are among the most frequently reported. Indeed, dysautonomia presented as orthostatic intolerance has gained room following recent reports linking postural orthostatic tachycardia syndrome (POTS) with PCC. Disturbances in heart rate (HR) and blood pressure (BP) during postural changes are the cornerstones of orthostatic intolerance seen in patients suffering from PCC. A subtype of POTS, hyperadrenergic POTS, has been widely studied because of its association with mast cell activation syndrome (MCAS). Although a causative relationship between PCC, hyperadrenergic POTS, and MCAS remains unrevealed, these syndromes can overlap. We want to propose here a correlation produced by a close-loop mechanism with positive feedback established after SARS-CoV-2 infection in a previously healthy young patient.

Generation of synthetic whole-slide image tiles of tumours from RNA-sequencing data via cascaded diffusion models.

Training machine-learning models with synthetically generated data can alleviate the problem of data scarcity when acquiring diverse and sufficiently large datasets is costly and challenging. Here we show that cascaded diffusion models can be used to synthesize realistic whole-slide image tiles from latent representations of RNA-sequencing data from human tumours. Alterations in gene expression affected the composition of cell types in the generated synthetic image tiles, which accurately preserved the distribution of cell types and maintained the cell fraction observed in bulk RNA-sequencing data, as we show for lung adenocarcinoma, kidney renal papillary cell carcinoma, cervical squamous cell carcinoma, colon adenocarcinoma and glioblastoma. Machine-learning models pretrained with the generated synthetic data performed better than models trained from scratch. Synthetic data may accelerate the development of machine-learning models in scarce-data settings and allow for the imputation of missing data modalities.

External validation of the PC-ECMO score in postcardiotomy veno-arterial extracorporeal membrane oxygenation.

Reliable stratification of the risk of early mortality after postcardiotomy veno-arterial extracorporeal membrane oxygenation (V-A-ECMO) remains elusive. In this study, we externally validated the PC-ECMO score, a specific risk scoring method for prediction of in-hospital mortality after postcardiotomy V-A-ECMO. Overall, 614 patients who required V-A-ECMO after adult cardiac surgery were gathered from an individual patient data meta-analysis of nine studies on this topic. The AUC of the logistic PC-ECMO score in predicting in-hospital mortality was 0.678 (95%CI 0.630-0.726; p < 0.0001). The AUC of the logistic PC-ECMO score in predicting on V-A-ECMO mortality was 0.652 (95%CI 0.609-0.695; p < 0.0001). The Brier score of the logistic PC-ECMO score for in-hospital mortality was 0.193, the slope 0.909, the calibration-in-the-large 0.074 and the expected/observed mortality ratio 0.979. 95%CIs of the calibration belt of fit relationship between observed and predicted in-hospital mortality were never above or below the bisector (p = 0.072). The present findings suggest that the PC-ECMO score may be a valuable tool in clinical research for stratification of the risk of patients requiring postcardiotomy V-A-ECMO.

Increase in hospital care at the end of life: Retrospective analysis of the last 20 years of life of a cohort of patients.

BACKGROUND: There is an increasing need for end-of-life care due to society's progressive aging. This study aimed to describe how hospitalizations evolve long-term and in the last months life of a cohort of deceased patients. METHODS: The study population were those who died in one year who lived in a district in southern Spain. The number of hospital stays over the previous 20 years and number of contacts with the emergency department, hospitalization, outpatient clinics, and medical day hospital in the last three months of life were determined. The analyses were stratified by age, sex, and pattern of functional decline. RESULTS: The study population included 1773 patients (82.5% of all who died in the district). The hospital stays during the last 20 years of life were concentrated in the last five years (66%) and specially in the last six months (32%). Eighty percent had contact with the hospital during their last three months of life. The older group had the minimun of stays over the last 20 years and contacts with the hospital in the last months of life. CONCLUSIONS: The majority of hospitalizations occur at the end of life and these admissions represent a significant part of an acute-care hospital's activity. The progressive prolongation of life does not have to go necessarily along with a proportional increase in hospital stays.

Epidemiological and clinical management aspects of pneumonias diagnosed in the emergency department in elderly patients in Spain: Results of the EDEN-29 study.

OBJECTIVES: To estimate the incidence of pneumonia diagnosis in elderly patients in Spanish emergency departments (ED), need for hospitalization, adverse events and predictive capacity of biomarkers commonly used in the ED. METHODS: Patients ≥65 years with pneumonia seen in 52 Spanish EDs were included. We recorded in-hospitaland 30-day mortality as adverse events, as well as intensive care unit (ICU) admission among hospitalizedpatients. Association of 10 predefined variables with adverse events was calculated and expressed as odds ratio (OR) with 95% confidence interval (CI), as well as predictive capacity of 5 commonly used biomarkers in the ED (leukocytes, hemoglobin, C-reactive protein, glucose, creatinine) was investigated using area under the receiver operating characteristic curve (AUC-ROC). RESULTS: 591 patients with pneumonia attended in the ED were included (annual incidence of 18,4 per 1000 inhabitants). A total of 78.0% were hospitalized. Overall, 30-day mortality was 14.2% and in-hospital mortality was 12.9%. Functional dependency was associated with both events (OR=4.453, 95%CI=2.361-8.400; and OR=3.497, 95%CI=1.578-7.750, respectively) as well as severe comorbidity (2.344, 1.363-4.030, and 2.463, 1.252-4.846, respectively). Admission to the ICU during hospitalization occurred in 3.5%, with no associated factors. The predictive capacity of biomarkers was only moderate for creatinine for ICU admission (AUC-ROC=0.702, 95% CI=0.536-0.869) and for leukocytes for post-discharge adverse event (0.669, 0.540-0.798). CONCLUSIONS: Pneumonia is a frequent diagnosis in elderly patients consulting in the ED. Their functional dependence and comorbidity is the factor most associated with adverse events. The biomarkers analyzed do not have a good predictive capacity for adverse events.

Pituitary Abscess Causing Panhypopituitarism in a Patient With Neurobrucellosis: Case Report.

Background/Objective: Pituitary abscess is an uncommon life-threatening disease that could lead to panhypopituitarism. It is important to suspect its prevalence in regions with endemic infectious diseases. Case Report: A 55-year-old man, a farmer, with a background of consumption of unpasteurized dairy products, presented with headache, impaired consciousness, and fever that started in February 2023. Initial test results were consistent with neuroinfection. Brain MRI showed ventriculitis; the pituitary gland was heterogeneous with the presence of an 8 × 8 mm abscess. The pituitary hormone axis was evaluated, and it showed results compatible with the results of panhypopituitarism with central hypothyroidism, central hypocortisolism, central hypogonadism, and growth hormone deficiency. Hormone replacement treatment with hydrocortisone and levothyroxine was started. The Rose Bengal test for Brucella spp. and 2-mercaptoethanol Brucella agglutination test showed positive results. After neurobrucellosis (NB) was diagnosed, antibiotic treatment was commenced. The patient was discharged 6 weeks later and treatment with prednisone, levothyroxine, recombinant somatropin, testosterone, as well as doxycycline, and rifampin was continued for another 4 months. Discussion: NB and pituitary abscess are rare manifestations of brucellosis and are challenging to diagnose due to their nonspecific clinical presentation and cerebrospinal fluid (CSF) findings. NB diagnosis relies on neurologic symptoms and serological evidence of Brucella infection. Magnetic resonance imaging is the preferred diagnostic tool for pituitary abscesses. Medical management may be sufficient, while transsphenoidal drainage is not always necessary. Hormonal deficits typically remain permanent. Conclusion: Pituitary abscess could be suspected in patients presenting with symptoms of neuroinfection, panhypopituitarism, and heterogenous image in the magnetic resonance imaging differential diagnosis. Opportune management can lead to reduced mortality and improved recovery of the pituitary hormone function.