Evolution of interconsultal activity to endocrinology and nutrition in hospitalization floor in a third level hospital.

INTRODUCTION: Endocrinology and Nutrition (EyN) is an outpatient and hospital medical specialty. This study aims to understand the evolution of the activity of interdepartmental consultation (IC) carried out by EyN in hospitalization floor of a third level hospital, comparing its evolution with other medical specialties, and comparing endocrine IC with nutritional IC. MATERIAL AND METHODS: Longitudinal and retrospective study which analyzes IC notes of EyN and other medical specialties between 01-01-2013 and 31-12-2022. RESULTS: A total of 76093 IC notes (12623 patients) were performed by the EyN service (average age 65.4 years; 59% male) with an average of 4.8 notes per patient. Average annual growth was 7% in notes and 4% in patients (versus 6% and 3% of all other medical services, differences statistically significant). Of all patients hospitalized for 4 or more days, EyN went from attending 7.9% (2013) to 12.3% (2022). 66% of the IC performed by EyN was for nutritional cause and 34% for other pathologies. CONCLUSIONS: The EyN service is the one that most patients attend in hospital IC activity, with growth over the last few years greater than other medical specialties. Nutritional pathology is the main reason for IC.

Changes in glucometric parameters in people living with diabetes users of the free-style libre 2 system before and after the update possibility to real-time glucose readings in real world practice.

In Spain, from October 10th, 2023, the FreeStyle Libre 2 system offers the possibility to automatically changed from isCGM to rtCGM with a system update. Our study aimed to evaluate the glucometric before and after that date. We didn't find significant changes in TIR, however time of use increased and TBR decreased.

Extensive colitis associated with ixekizumab.

We present the clinical case of a 56-year-old former smoker female, with a family history of maternal ulcerative colitis and personal history of ankylosing spondylitis treated with Ixekizumab for 3 months, who was admitted for fever, left iliac fossa pain and diarrhea without pathological products of 2 weeks of evolution. Abdominopelvic computed tomography scan identified pancolitis. Complete colonoscopy revealed continuous involvement of the proximal colon (right and transverse colon presented deep ulcerations and mucosal friability) with preservation of the terminal ileum. After many complementary tests and according to the clinical context, the diagnosis of extensive colitis associated with IL-17 inhibitor was established.

Extraosseous Ewing's sarcoma of the pancreas.

We present the clinical case of a 21-year-old male with abdominal pain in the left hypochondrium radiating to the ipsilateral lumbar area and a weight loss of 2kg over a month, secondary to a large palpable intra-abdominal mass in the examination. TAC revealed a large solid mass with necrotic-cystic component which depended of the pancreas, infiltrated the spleen, enveloped the celiac trunk and affected to the splenic vases. Inmunohistochemical and molecular study confirmed the diagnosis extraosseus Ewing sarcoma (EES).

Dysphagia secondary to neuroendocrine carcinoma: a rare esophageal tumor.

We present two clinical cases, a 68-year-old male and a 55-year-old female, who are being studied for progressive solid food dysphagia. The initial gastroscopy revealed a polypoid lesion in the first case and a partially stenosing lesion in the second case. Both lesions were located in the mid-esophagus and presented a normal mucosa. Histological diagnosis confirmed an esophageal neuroendocrine carcinoma (NEC) of large cell and small cell types, respectively.

Risk factors for intraoperative hypertensive crisis in patients with pheochromocytomas and sympathetic paragangliomas.

PURPOSE: To identify presurgical and surgical risk factors for intraoperative hypertensive crisis in patients with pheochromocytomas and sympathetic paragangliomas (PGLs) (PPGLs). METHODS: Retrospective multicenter cohort study of patients with PPGLs from 18 tertiary hospitals. Intraoperative hypertensive crisis was defined as systolic blood pressure (SBP) greater than 200 mmHg lasting more than 1 min and postoperative hypertensive crisis as SBP greater than 180 mmHg or diastolic blood pressure (DBP) greater than 110 mmHg. RESULTS: A total of 296 surgeries were included. Alpha presurgical blockade was employed in 93.2% of the cases and beta-adrenergic in 53.4%. Hypertensive crisis occurred in 20.3% ( n  = 60) of the surgeries: intraoperative crisis in 56 and postoperative crisis in 6 cases (2 cases had both types of crises). We identified as risk factors of intraoperative hypertensive crisis, absence of presurgical glucocorticoid therapy (odds ratio [OR] 3.48; 95% confidence interval [CI] 1.19-10.12) higher presurgical SBP (OR 1.22 per each 10 mmHg, 95% CI 1.03-1.45), a larger tumor size (OR 1.09 per each 10 mm, 95% CI 1.00-1.19) and absence of oral sodium repletion (OR 2.59, 95% CI 1.25-5.35). Patients with hypertensive crisis had a higher rate of intraoperative bleeding ( P  < 0.001), of intraoperative hemodynamic instability ( P  < 0.001) and of intraoperative hypotensive episodes ( P  < 0.001) than those without hypertensive crisis. CONCLUSION: Intraoperative hypertensive crisis occurs in up to 20% of the PPGL resections. Patients not pretreated with glucocorticoid therapy before surgery, with larger tumors and higher presurgical SBP and who do not receive oral sodium repletion have a higher risk for developing hypertensive crisis during and after PPGL surgery.

Local recurrence and metastatic disease in pheochromocytomas and sympathetic paragangliomas.

Purpose: To evaluate the rate of recurrence among patients with pheochromocytomas and sympathetic paragangliomas (PGLs; together PPGLs) and to identify predictors of recurrence (local recurrence and/or metastatic disease). Methods: This retrospective multicenter study included information of 303 patients with PPGLs in follow-up in 19 Spanish tertiary hospitals. Recurrent disease was defined by the development of local recurrence and/or metastatic disease after initial complete surgical resection. Results: A total of 303 patients with PPGLs that underwent 311 resections were included (288 pheochromocytomas and 15 sympathetic PGLs). After a median follow-up of 4.8 years (range 1-19), 24 patients (7.9%) had recurrent disease (3 local recurrence, 17 metastatic disease and 4 local recurrence followed by metastatic disease). The median time from the diagnosis of the PPGL to the recurrence was of 11.2 months (range 0.5-174) and recurrent disease cases distributed uniformly during the follow-up period. The presence of a pathogenic variant in SDHB gene (hazard ratio [HR] 13.3, 95% CI 4.20-41.92), higher urinary normetanephrine levels (HR 1.02 per each increase in standard deviation, 95% CI 1.01-1.03) and a larger tumor size (HR 1.01 per each increase in mm, 95% CI 1.00-1.02) were independently associated with disease recurrence. Conclusion: The recurrence of PPGLs occurred more frequently in patients with SDHB mutations, with larger tumors and with higher urinary normetanephrine levels. Since PPGL recurrence may occur at any time after the initial PPGL diagnosis is performed, we recommend performing a strict follow-up in all patients with PPGLs, especially in those patients with a higher risk of recurrent disease.

An Integrated CT and MRI Imaging Model to Differentiate between Adrenal Adenomas and Pheochromocytomas.

PURPOSE: to perform an external validation of our predictive model to rule out pheochromocytoma (PHEO) based on unenhanced CT in a cohort of patients with PHEOs and adenomas who underwent adrenalectomy. METHODS: The predictive model was previously developed in a retrospective cohort of 1131 patients presenting with adrenal lesions. In the present study, we performed an external validation of the model in another cohort of 214 patients with available histopathological results. RESULTS: For the external validation, 115 patients with PHEOs and 99 with adenomas were included. Our previously described predictive model combining the variables of high lipid content and tumor size in unenhanced CT (AUC-ROC: 0.961) had a lower diagnostic accuracy in our current study population for the prediction of PHEO (AUC: 0.750). However, when we excluded atypical adenomas (with Hounsfield units (HU) > 10, n = 39), the diagnostic accuracy increased to 87.4%. In addition, in the whole cohort (including atypical adenomas), when MRI information was included in the model, the diagnostic accuracy increased to up to 85% when the variables tumor size, high lipid content in an unenhanced CT scan, and hyperintensity in the T2 sequence in MRI were included. The probability of PHEO was <0.3% for adrenal lesions <20 mm with >10 HU and without hyperintensity in T2. CONCLUSION: Our study confirms that our predictive model combining tumor size and lipid content has high reliability for the prediction of PHEO when atypical adrenal lesions are excluded. However, for atypical adrenal lesions with >10 HU in an unenhanced CT scan, MRI information is necessary for a proper exclusion of the PHEO diagnosis.

Cash flow management and its effect on firm performance: Empirical evidence on non-financial firms of China.

The main purpose of this research is to investigate the impact of changes in cash flow measures and metrics on firm financial performance. The study uses generalized estimating equations (GEEs) methodology to analyze longitudinal data for sample of 20288 listed Chinese non-financial firms from the period 2018:q2-2020:q1. The main advantage of GEEs method over other estimation techniques is its ability to robustly estimate the variances of regression coefficients for data samples that display high correlation between repeated measurements. The findings of study show that the decline in cash flow measures and metrics bring significant positive improvements in the financial performance of firms. The empirical evidence suggests that performance improvement levers (i.e. cash flow measures and metrics) are more pronounced in low leverage firms, suggesting that changes in cash flow measures and metrics bring more positive changes in low leverage firms' financial performance relatively to high leveraged firms. The results hold after mitigating endogeneity based on dynamic panel system generalized method of moments (GMM) and sensitivity analysis considering the robustness of main findings. The paper makes significant contribution to the literature related to cash flow management and working capital management. Since, this paper is among few to empirically study, how cash flow measures and metrics are related to firm performance from dynamic stand point especially from the context of Chinese non-financial firms.

Caracterización de madres de pacientes con exposición perinatal al Virus de Inmunodeficiencia Humana

La mayor incidencia de la infección por el virus de inmunodeficiencia humana (VIH) en mujeres ha tenido un impacto directo en la transmisión vertical, situación que puede ser evitada con un adecuado control prenatal. Objetivo: Determinar características demográficas, epidemiológicas y obstétricas de madres de pacientes con exposición perinatal al VIH. Métodos: Se realizó un estudio retrospectivo, observacional, transversal y analítico. Se incluyeron madres con infección por VIH de transmisión horizontal, cuyos hijos con exposición perinatal, nacidos entre 2001 y 2020, fueron atendidos en la Unidad VIH del Hospital de Niños "J.M. de los Ríos" (Caracas-Venezuela). La información fue obtenida de la Base de Datos Interna. Las madres fueron agrupadas según la década de nacimiento del hijo (2001-2010 o 2011-2020). El análisis estadístico incluyó la prueba de Chi cuadrado. Resultados: Se estudiaron 805 madres. La edad promedio al nacer fue 26,4 años; el 8,6 % (n=69/803) era adolescente. El control prenatal fue inadecuado o inexistente en 59,7 % (n=463/776). La identificación de la infección materna fue obtenida durante o después del nacimiento en 36,4 % (n=280/769), con diferencias entre décadas: 26,7 % en la primera y 42,5 % en la segunda (p<0,01). En el 90,4 % (n=253/280) de este grupo el diagnóstico se obtuvo posterior al nacimiento. Conclusiones: La edad promedio de las madres fue 26,4 años. Aproximadamente 50 % tuvo control prenatal inadecuado o inexistente. Alrededor de un tercio obtuvo el diagnóstico después del embarazo, con significativo mayor porcentaje en la segunda década. Sólo en 1/10 madres de este grupo, la infección fue identificada al nacimiento.

The higher incidence of human immunodeficiency virus (HIV) infection in women has had a direct impact on vertical transmission, situation that can be avoided with an adequate prenatal control. Objective: To determine demographic, epidemiological, and obstetric characteristics of mothers of children with perinatal exposure to HIV. Methods: A retrospective, observational, cross-sectional and analytical study was carried out. It was included mothers, with horizontally transmitted HIV infection, whose children with perinatal exposure, born between 2001 and 2020, were treated at the HIV Unit of the Children's Hospital "J.M. de los Ríos" (Caracas-Venezuela). The information was obtained from the Unit Internal Database. The mothers were grouped according to the decade of her child's birth (2001-2010 or 2011-2020). Chi square test was performed for statistical analysis. Results: A total of 805 mothers were studied. The average age at birth was 26.4 years; 8.6 % (n=69/803) were adolescents. Prenatal care was inadequate or non-existent in 59.7 % (n=463/776). Identification of maternal infection was obtained during or after birth in 36.4 % (n=280/769), with differences between decades: 26.7 % in the first and 42.5 % in the second (p<0.01). In 90.4 % (n=253/280) of this group, the diagnosis was obtained after birth. Conclusions: The average age of the mothers was 26.4 years. Approximately 50 % had inadequate or nonexistent prenatal care. About a third were diagnosed after pregnancy, with a significantly higher percentage in the second decade. In only 1/10 mothers of this group the infection was identified at birth.

The clinical and molecular spectrum of the KDM6B-related neurodevelopmental disorder.

De novo variants are a leading cause of neurodevelopmental disorders (NDDs), but because every monogenic NDD is different and usually extremely rare, it remains a major challenge to understand the complete phenotype and genotype spectrum of any morbid gene. According to OMIM, heterozygous variants in KDM6B cause "neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities." Here, by examining the molecular and clinical spectrum of 85 reported individuals with mostly de novo (likely) pathogenic KDM6B variants, we demonstrate that this description is inaccurate and potentially misleading. Cognitive deficits are seen consistently in all individuals, but the overall phenotype is highly variable. Notably, coarse facies and distal skeletal anomalies, as defined by OMIM, are rare in this expanded cohort while other features are unexpectedly common (e.g., hypotonia, psychosis, etc.). Using 3D protein structure analysis and an innovative dual Drosophila gain-of-function assay, we demonstrated a disruptive effect of 11 missense/in-frame indels located in or near the enzymatic JmJC or Zn-containing domain of KDM6B. Consistent with the role of KDM6B in human cognition, we demonstrated a role for the Drosophila KDM6B ortholog in memory and behavior. Taken together, we accurately define the broad clinical spectrum of the KDM6B-related NDD, introduce an innovative functional testing paradigm for the assessment of KDM6B variants, and demonstrate a conserved role for KDM6B in cognition and behavior. Our study demonstrates the critical importance of international collaboration, sharing of clinical data, and rigorous functional analysis of genetic variants to ensure correct disease diagnosis for rare disorders.

Evolution of the choice of places in Endocrinology and Nutrition in the Spanish exam for accessing to the resident physicians training program 2001-2022 measured with the quotation index.

INTRODUCTION: The comparison between specialties or the analysis of evolution over time of a speciality in the Spanish exam for accessing to the resident physicians training programme (RPTP) is difficult due to the changing of the number of places offered. In this paper we describe two parameters (quotation index and quotation order) that objectify the relationship between supply and demand for places in a given medical speciality in a RPTP call and analyse the evolution of the speciality of Endocrinology and Nutrition (E&N). MATERIAL AND METHODS: We analysed the evolution of the supply/demand ratio for the speciality of E&N in the 2001-2022 RPTP calls using the quotation index and quotation order. An increase in the quotation order implies a worsening of the supply/demand ratio. Robust correlation analysis between year and quoatation orden is used. RESULTS: E&N shows a worsening in the RPTP choice, both in relation to all specialties offered and in relation to specialties of medical area (robust correlation coefficient year-quotation order 0.72 (p=0.0002) if all specialties are considered and 0.80 (p<0.0001) if only medical area specialties are considered). CONCLUSIONS: The specialty E&N has shown a negative evolution in the choice of RPTP, objectified through the quotation index and the quotation order, both in relation to all the specialties offered and in relation to all the specialties of the medical area, although it is still among the most sought-after medical specialties in the medical area.

Genetic Study in Pheochromocytoma: Is It Possible to Stratify the Risk of Hereditary Pheochromocytoma?

INTRODUCTION: It is estimated that 30-40% of patients with apparently sporadic pheochromocytomas (PHEOs) have an inherited predisposition syndrome. The aim of our study was to develop a predictive model of hereditary PHEO based on the clinical, hormonal, and radiological features present at the diagnosis of patients with PHEOs. METHODS: A retrospective multicenter cohort study of patients with PHEOs with available genetic study from 18 tertiary hospitals. Clinical, biochemical, and radiological features were used to build a multivariate logistic regression model. The estimation of all possible equations was used to select the model with the best diagnostic accuracy (lower Akaike index). RESULTS: A total of 245 patients were included: 169 (69.0%) patients with sporadic PHEOs and 76 (31%) with hereditary PHEOs. The parsimonious predictive model with the highest diagnostic accuracy for the prediction of hereditary PHEO combined the variables age, non-cardiovascular disease, urinary norepinephrine levels, and tumor size. The area under the ROC curve of this model was 0.800 (0.705-0.887). Based on the predictive model, the probability of hereditary PHEO in patients older than 60 years with cardiovascular disease, high levels of urinary norepinephrine and unilateral PHEOs >60 mm was <2%. And if the age was above 80 years, lower than 1%. The probability of sporadic PHEO linearly increased with age (MH Test for linear Trend: χ2 (1) = 30.05; p < 0.001). CONCLUSION: In certain populations such as old patients with cardiovascular disease, with high levels of urinary norepinephrine and large tumors in which the probability of hereditary PHEO is very low, genetic testing could be avoided in the absence of specific suspicion.

Glycemic disorders in patients with pheochromocytomas and sympathetic paragangliomas.

The objective of our study was to determine the prevalence of glycemic disorders (diabetes mellitus and prediabetes) in patients with pheochromocytomas and sympathetic paragangliomas (PPGLs) and identify risk factors for their development and the likelihood of their resolution after surgery. A multicentric retrospective study of patients with PPGLs submitted to surgery between 2000 and 2021 in 17 Spanish hospitals was performed. Diabetes-specific data were collected at diagnosis, in the immediate- and long-term postsurgical follow-up. A total of 229 patients with PPGLs were included (218 with pheochromocytomas and 11 with sympathetic paragangliomas). Before surgery, glycemic disorders were diagnosed in 35.4% of the patients (n = 81): 54 with diabetes and 27 with prediabetes. The variables independently associated with a higher risk of glycemic disorders were sporadic PPGL (odds ratio (OR) = 3.26 (1.14-9.36)) and hypertension (OR = 3.14 (1.09-9.01)). A significant decrease in fasting plasma glucose and HbA1c levels was observed after surgery, in the short-term and long-term follow-up (P < 0.001). After a median follow-up of 48.5 months (range 3.3-168.9), after surgery, 52% of diabetic and 68% of prediabetic patients experienced a complete resolution. Lower body mass index (BMI) (P = 0.001), lower glucose levels (P = 0.047) and shorter duration of diabetes prior to surgery (P = 0.021) were associated with a higher probability of diabetes resolution. In conclusion, glycemic disorders in patients with PPGLs are present in more than a third of them at diagnosis. Sporadic PPGLs and hypertension are risk factors for their development. More than 50% of cases experience a complete resolution of the glycemic disorder after resection of the PPGLs.

The Clonal Relationship Between the Ductal and Lobular Components of Mixed Ductal-Lobular Carcinomas Suggested a Ductal Origin in Most Tumors.

The relationship between the ductal and lobular components of invasive ductolobular carcinomas (IDLC) has not been fully elucidated. In this study, the molecular alterations of both components were analyzed in a series of 20 IDLC that were selected, not only by morphologic criteria, but also by the loss of E-cadherin expression in the lobular component. We found that 80% of tumors shared alterations of driver genes in both components, being PIK3CA the most common alteration. In addition, 45% of IDLC carried CDH1 mutations in their lobular component that were absent in the ductal component. Fluorescent in situ hybridization analysis of the CDH1 gene excluded homozygous CDH1 loss as a frequent cause of E-cadherin loss in tumors without CDH1 mutations. In addition, no pathogenic mutations of catenin genes were detected in this series of tumors. In 25% of tumors, actionable mutations in PIK3CA , AKT1 , and ERBB2 were found in only 1 component. Altogether, our results confirm that most IDLC derive from invasive carcinoma of no special type, in which a population of cells lose E-cadherin and acquire a lobular phenotype. The frequency of CDH1 mutations in IDLC appears to be lower than in conventional invasive lobular carcinomas, suggesting the implication of alternative mechanisms of E-cadherin loss. Moreover, molecular heterogeneity between ductal and lobular areas suggests the need for molecular characterization of both components to guide targeted therapies.