Angiopoietin-2, vascular endothelial growth factor family, and heparin binding endothelial growth factor are associated with subclinical atherosclerosis in rheumatoid arthritis.

Introduction: Patients with RA are at a higher risk of developing CV diseases than the general population. The precise mechanisms are still unknown. We evaluated the associations between 8 plasma growth factors (GFs) (angiopoietin-2, EGF, HB-EGF, PLGF, TGF-α, VEGFa, VEGFc, and VEGFd) and subclinical arteriosclerosis in RA patients. Materials and methods: A total of 199 patients with RA treated at the Hospital Universitari Sant Joan de Reus (Spain) between 2011 and 2015 were included in this cross-sectional study. Carotid intima media thickness (cIMT), carotid plaque presence (cPP) and pulse wave velocity (PWV) were measured. GFs were measured with Bio-Plex Pro Human Cancer Biomarker Panel 2 (Bio-Rad). Multivariate models and partial least square discriminant analysis (PLS-DA) were used for analysis (RStudio, version 4.0.1). Results: Multivariate models showed that angiopoietin-2 was associated with cPP and PWV in the overall cohort (OR = 1.53 and ß = 0.20, respectively). VEGFc (ß = 0.29), VEGFa (ß = 0.26) and HB-EGF (ß = 0.22) were also associated with PWV. VEGFa (OR = 2.36), VEGFd (OR = 2.29), EGF (OR = 2.62), PLGF (OR = 2.54), and HB-EGF (OR = 2.24) were associated with cPP in men. According to PLS-DA, GFs were able to distinguish between patients with and without cPP in the overall cohort, male cohort, and female cohort. In women, angiopoietin-2 was associated with PWV (ß = 0.18). Conclusions: The selected GFs were closely related to atherosclerosis in patients with RA and are potential predictors of CV disease in patients with RA.

Plasma Expression of Carotid Plaque Presence-Related MicroRNAs Is Associated with Inflammation in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is associated with problems beyond the joints such as cardiovascular (CV) disease. MicroRNA-24, -146 and -Let7a are associated with carotid plaque presence in RA patients. We evaluated whether these microRNAs were involved in the inflammatory state of RA, and we studied their gene targets to understand their role in inflammation and atherosclerosis. A total of 199 patients with RA were included. Inflammatory variables such as disease activity score 28 (DAS28) and erythrocyte sedimentation rate (ESR) were quantified. MicroRNAs were extracted from plasma and quantified with qPCR. Multivariate models and classification methods were used for analysis. The multivariate models showed that diminished expression of microRNA-146 was associated with inferior levels of DAS28-ESR, and the decreased expression of microRNA-24, -146 and -Let7a were associated with lowered ESR in the overall cohort. When microRNAs were evaluated globally, a global increase was associated with increased DAS28-ESR and ESR in the overall cohort. Sex-stratified analyses showed different associations of these microRNAs with the inflammatory variables. Finally, random forest models showed that microRNAs have a pivotal role in classifying patients with high and low inflammation. Plasmatic expressions of microRNA-24, -146 and -Let7a were associated with inflammatory markers of RA. These microRNAs are associated with both inflammation and atherosclerosis and are potential therapeutic targets for RA.

Maternal height as a predictor of glucose intolerance in the postpartum and its relationship with maternal pre-gestational weight.

PURPOSE: Short stature predicts higher risk of developing type 2 diabetes. We studied the association between height and glucose intolerance in women with gestational diabetes mellitus (GDM) and whether this association differed according to body mass index (BMI). METHODS: Retrospective study of the Portuguese GDM registry. EXCLUSION CRITERIA: missing data on postpartum oral glucose tolerance test (OGTT) or BMI. ENDPOINT: postpartum glucose intolerance (diabetes mellitus or prediabetes on the 6-8 weeks postpartum OGTT). Women were divided by mean height and compared. A multivariate logistic regression was used, and the analysis was stratified by BMI (cut-off: 30 kg/m2) and interaction was tested. RESULTS: We included 7402 women; mean height was 161.9 ± 6.2 cm. Taller women had lower BMI and lower rates of glucose intolerance (6.8 vs. 8.8%, p = 0.002). Women with BMI < 30 kg/m2 were taller than those with obesity. Height associated with glucose intolerance. The multivariate adjusted OR of glucose intolerance was 0.98 (95% CI 0.96-0.99), p = 0.001, per 1 cm increase in height. This association was only observed in women with BMI < 30 kg/m2: OR 0.97 (95% CI 0.95-0.99), < 0.001. There was no such association in women with BMI ≥ 30 kg/m2: OR 0.99 (95% CI 0.97-1.02), p = 0.65. P for interaction between BMI and height was 0.09. CONCLUSIONS: In non-obese pre-gestational women, height is inversely associated with postpartum glucose intolerance. Per 1 cm increase in height, women present a 3% decrease in the risk of developing diabetes mellitus or prediabetes.

A panel of plasma microRNAs improves the assessment of surrogate markers of cardiovascular disease in rheumatoid arthritis patients.

OBJECTIVE: Patients with RA present increased risk of cardiovascular (CV) disease compared with the general population. Moreover, CV risk factors that have a causal relationship with atherosclerosis do not seem to fully explain the accelerated process that they exhibit. We evaluated the association of a 10 microRNAs panel with surrogate markers of subclinical arteriosclerosis [carotid intima-media thickness (cIMT), carotid plaque presence (cPP), pulse wave velocity (PWV) and distensibility] in a cohort of RA patients. MATERIAL AND METHODS: A total of 199 patients with RA were included. Surrogate markers of arteriosclerosis were measured with My Lab 60 X-Vision sonographer. MicroRNAs were extracted from plasma and quantified with qPCR. Multivariate models and classification methods were performed. RESULTS: Multivariate models showed that microRNAs-24 (ß = 15.48), 125a (ß = 9.93), 132 (ß = 11.52), 146 (ß = 15.12), 191 (ß = 13.25) and 223 (ß = 13.30) were associated with cIMT globally. MicroRNA-24 [odds ratio (OR) = 0.41], 146 (OR = 0.36) and Let7a (OR = 0.23) were associated with cPP in men. Including the microRNAs in a partial least square discriminant analysis model properly classified men with and without cPP. MicroRNA-96 (ß = -0.28) was associated with PWV in male patients. Finally, several miRNAs were also associated with cIMT, cPP and arterial stiffness in the high DAS28 group and in the earlier tertile groups of disease duration. CONCLUSION: Plasmatic expression of microRNA-24, 96, 103, 125a, 132, 146, 191, 223 and Let7a were associated with surrogate markers of CV disease and could be predictors of CV risk in patients with RA.

Severity of influenza illness by seasonal influenza vaccination status among hospitalised patients in four South American countries, 2013-19: a surveillance-based cohort study.

BACKGROUND: Although several studies have reported attenuated influenza illness following influenza vaccination, results have been inconsistent and have focused predominantly on adults in the USA. This study aimed to evaluate the severity of influenza illness by vaccination status in a broad range of influenza vaccine target groups across multiple South American countries. METHODS: We analysed data from four South American countries (Argentina, Brazil, Chile, and Paraguay) participating in REVELAC-i, a multicentre, test-negative design, vaccine effectiveness network including 41 sentinel hospitals. Individuals hospitalised at one of these centres with severe acute respiratory infection were tested for influenza by real-time RT-PCR, and were included in the analysis if they had complete information about their vaccination status and outcomes of their hospital stay. We used multivariable logistic regression weighted by inverse probability of vaccination and adjusted for antiviral use, duration of illness before admission, and calendar week, to calculate the adjusted odds ratios (aORs) of intensive care unit (ICU) admission and in-hospital death (and combinations of these outcomes) among influenza-positive patients by vaccination status for three target groups: young children (aged 6-24 months), adults (aged 18-64 years) with pre-existing health conditions, and older adults (aged ≥65 years). Survival curves were used to compare length of hospital stay by vaccination status in each target group. FINDINGS: 2747 patients hospitalised with PCR-confirmed influenza virus infection between Jan 1, 2013, and Dec 8, 2019, were included in the study: 649 children (70 [10·8%] fully vaccinated, 193 [29·7%] partially vaccinated) of whom 87 (13·4%) were admitted to ICU and 12 (1·8%) died in hospital; 520 adults with pre-existing medical conditions (118 [22·7%] vaccinated), of whom 139 (26·7%) were admitted to ICU and 55 (10·6%) died in hospital; and 1578 older adults (609 [38·6%] vaccinated), of whom 271 (17·2%) were admitted to ICU and 220 (13·9%) died in hospital. We observed earlier discharge among partially vaccinated children (adjusted hazard ratio 1·14 [95% CI 1·01-1·29]), fully vaccinated children (1·24 [1·04-1·47]), and vaccinated adults with pre-existing medical conditions (1·78 [1·18-2·69]) compared with their unvaccinated counterparts, but not among vaccinated older adults (0·82 [0·65-1·04]). Compared with unvaccinated individuals, lower odds of ICU admission were found for partially vaccinated children (aOR 0·64 [95% CI 0·44-0·92]) and fully vaccinated children (0·52 [0·28-0·98]), but not for adults with pre-existing conditions (1·25 [0·93-1·67]) or older adults (0·88 [0·72-1·08]). Lower odds of in-hospital death (0·62 [0·50-0·78]) were found in vaccinated versus unvaccinated older adults, with or without ICU admission, but did not differ significantly in partially vaccinated (1·35 [0·57-3·20]) or fully vaccinated young children (0·88 [0·16-4·82]) or adults with pre-existing medical conditions (1·09 [0·73-1·63]) compared with the respective unvaccinated patient groups. INTERPRETATION: Influenza vaccination was associated with illness attenuation among those hospitalised with influenza, although results differed by vaccine target group. These findings might suggest that attenuation of disease severity might be specific to certain target groups, seasons, or settings. FUNDING: US Centers for Disease Control and Prevention. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.

First insights in terrestrial mammals monitoring in the Candelaria and Machay Reserves in the Ecuadorian Tropical Andes.

Habitat disturbance leads to biodiversity decline and modifications in the landscape structure and composition, affecting both dispersal movements and ecological processes at different temporal and spatial scales. The Ecuadorian Tropical Andes harbour suitable habitats for the distribution of a wide variety of species; however, there is a lack of studies focused on mammal diversity and its association with the habitat attributes in the central-eastern slopes. Here, we reported the diversity of terrestrial mammals recorded between 2019 and 2021 in a camera-trap monitoring study in the Candelaria and Machay reserves in the upper basin of the Pastaza River, Ecuador. We performed site-occupancy probability analysis to assess the influence of spatial variables in the species' occurrence and also, based on natural marks, we reported preliminary findings in Andean bear individual identification. We detected 22 species of terrestrial mammals. Alpha diversity was similar between reserves with slightly higher species richness in Machay. Evenness indices showed unequal species distribution, with the Andean bear and domestic dogs exhibiting greater dominance. In addition, species composition was dissimilar between reserves, where the species turnover mostly explained the beta diversity. We observed that Andean bear and puma detections increased according to the natural vegetation cover. Conversely, domestic dogs were frequently detected in cells with an increasing proportion of pastures and crops. Additionally, we identified 26 Andean bears and six individuals recaptured during our study. Our results caution about the disturbance derived from human activities since we recorded unprecedented detections of domestic dogs in wild habitats. Nonetheless, it highlights the importance of private conservation areas (e.g. Candelaria, Machay and others) for supporting the occurrence and dispersal of terrestrial mammal species between larger areas in the upper basin of the Pastaza River.

Dietary parameters in patients with drug allergy: Assessing dietary inflammatory index.

BACKGROUND: Research on the increasing incidence of allergic diseases evidenced the role of diet as a potential key factor. Diet can modulate the low-grade systemic inflammation related to obesity and several diseases. There are no published data on drug allergy. AIM: To investigate a potential association between diet, including dietary inflammatory index (DII), and drug allergy. Also, to evaluate correlations between diet and obesity, inflammatory and metabolic parameters in patients with drug allergy. METHODS: Ninety consecutive patients studied for suspected drug allergy were evaluated in terms of dietary parameters, anthropometric measurements, bioimpedance and biochemical analysis. DII was calculated based on information collected from a food frequency questionnaire. RESULTS: After diagnostic work-up, 39 patients had confirmed drug allergy and 45 excluded, representing the study group and the control group, respectively. The majority (79%) were female, with mean age of 39.58±13.3 years. The 84 subjects revealed an anti-inflammatory diet pattern. No significative difference was found in DII scores between drug allergic patients and controls (-3.37±0.95 vs -3.39±0.86, p = 0.985). However, the patients with drug allergy revealed higher obesity and inflammatory parameters. A significative negative correlation was found between DII and adiponectin levels, in the control group (r = -0.311, p = 0.040). In the patient group, a significative positive correlation was observed between DII and triglycerides (r = 0.359, p = 0.032). No other correlations were found between DII and the assessed parameters. Patients with drug allergy presented a significative higher intake of mono-unsaturated fatty-acids comparing to controls (19.8±3.7 vs 17.8 ± 4.0, p = 0.021). No other statistically significant differences were achieved in dietary parameters, between patients and controls. CONCLUSION: The population assessed in this study revealed an anti-inflammatory diet profile. Although we have found in a previous work that the same patients with drug allergy revealed higher obesity and inflammatory parameters, the DII did not allow to distinguish between patients with drug allergy or controls. The DII scores correlated with triglycerides levels in the drug allergy patients and inversely with adiponectin levels in the control group. Larger studies are needed to clarify the potential role of the diet in drug allergy and its outcomes.

Male gender as a poor prognostic factor in Medullary Thyroid Carcinoma: behaviour or biological difference?

PURPOSE: Due to the low incidence and heterogeneous behaviour of medullary thyroid carcinoma (MTC), its prognostic factors are still not well stablished. While several large studies have investigated the impact of gender in differentiated thyroid cancer (DTC), its role in MTC outcomes remains controversial. We aim to identify MTC prognostic features, specially focusing on the role of gender. METHODS: Retrospective analysis of 76 patients diagnosed with MTC between 1984 and 2018 at a Portuguese Comprehensive Cancer Center. RESULTS: Patients presented a median age at diagnosis of 49 years and multiple endocrine neoplasia type 2 (MEN2) was identified in 27.6% of them, with those individuals being significantly younger (P<0.001). Most cases were diagnosed as stage IV disease (46.9%), except for the subgroup detected through pre-symptomatic genetic screening (55.6% at stage I). The 5- and 10-year survival rates were 87.6% and 75.6%, respectively. Univariate analysis identified male gender (P=0.010), age ≥45 years (P=0.007), presence of distant metastasis at diagnosis (P<0.01), capsule invasion (P=0.004), extrathyroidal invasion (P=0.003) and absence of biochemical cure after surgery (P=0.042) as having a negative impact on prognosis. On multivariate analysis, male gender (P=0.046) remained an independent predictor of mortality, as well as an older age (P<0.001) and the presence of distant metastases (P=0.012). CONCLUSIONS: Male gender independently predicted worse survival in MTC patients even after adjusting for age and disease stage. The few older studies on the topic pointed to a behavioural explanation regarding medical care seeking patterns by men, but our study and newer genetic and basic-science oriented publications raise the possibility of a true biological difference between genders in the tumourigenesis of MTC that should me further investigated.

Comment on Aaseth et al. Circulating Lipoproteins in Subjects with Morbid Obesity Undergoing Bariatric Surgery with Gastric Bypass or Sleeve Gastrectomy. Nutrients 2022, 14, 2381.

We read with great interest the paper by Jan O. Aaseth et al. entitled "Circulating Lipoproteins in Subjects with Morbid Obesity Undergoing Bariatric Surgery with Gastric Bypass or Sleeve Gastrectomy" where changes in lipid profile after bariatric surgery were reported [...].

Plasma expression of microRNA-425-5p and microRNA-451a as biomarkers of cardiovascular disease in rheumatoid arthritis patients.

To validate in a cohort of 214 rheumatoid arthritis patients a panel of 10 plasmatic microRNAs, which we previously identified and that can facilitate earlier diagnosis of cardiovascular disease in rheumatoid arthritis patients. We identified 10 plasma miRs that were downregulated in male rheumatoid arthritis patients and in patients with acute myocardial infarction compared to controls suggesting that these microRNAs could be epigenetic biomarkers for cardiovascular disease in rheumatoid arthritis patients. Six of those microRNAs were validated in independent plasma samples from 214 rheumatoid arthritis patients and levels of expression were associated with surrogate markers of cardiovascular disease (carotid intima-media thickness, plaque formation, pulse wave velocity and distensibility) and with prior cardiovascular disease. Multivariate analyses adjusted for traditional confounders and treatments showed that decreased expression of microRNA-425-5p in men and decreased expression of microRNA-451 in women were significantly associated with increased (ß = 0.072; p = 0.017) and decreased carotid intima-media thickness (ß = -0.05; p = 0.013), respectively. MicroRNA-425-5p and microRNA-451 also increased the accuracy to discriminate patients with pathological carotid intima-media thickness by 1.8% (p = 0.036) in men and 3.5% (p = 0.027) in women, respectively. In addition, microRNA-425-5p increased the accuracy to discriminate male patients with prior cardiovascular disease by 3% (p = 0.008). Additionally, decreased expression of microRNA-451 was significantly associated with decreased pulse wave velocity (ß = -0.72; p = 0.035) in overall rheumatoid arthritis population. Distensibility showed no significant association with expression levels of the microRNAs studied. We provide evidence of a possible role of microRNA-425-5p and microRNA-451 as useful epigenetic biomarkers to assess cardiovascular disease risk in patients with rheumatoid arthritis.

Third trimester HbA1c and the association with large-for-gestational-age neonates in women with gestational diabetes

ABSTRACT Objective: To evaluate the association between HbA1c levels measured in the third trimester and the risk for large for gestational age (LGA) in neonates of mothers affected by gestational diabetes mellitus (GDM). Secondarily, we aimed to identify an ideal cut-off for increased risk of LGA amongst pregnant women with GDM. Materials and methods: Observational retrospective review of singleton pregnant women with GDM evaluated in a diabetes and pregnancy clinic of a tertiary and academic hospital. From January/2011 to December/2017, 1,085 pregnant women underwent evaluation due to GDM, of which 665 had an HbA1c test in the third trimester. A logistic regression model was performed to evaluate predictors of LGA. A receiver-operating-characteristic (ROC) curve was used to evaluate the predictive ability of third trimester HbA1c for LGA identification. Results: A total of 1,085 singleton pregnant women were evaluated during the study period, with a mean age of 32.9 ± 5.3 years. In the multivariate analysis, OGTT at 0 minutes (OR: 1.040; CI 95% 1.006-1.076, p = 0.022) and third trimester HbA1c (OR: 4.680; CI 95% 1.210-18.107, p = 0.025) were associated with LGA newborns. Using a ROC curve to evaluate the predictive ability of third trimester HbA1c for LGA identification, the optimal HbA1c cut-off point was 5.4% where the sensitivity was 77.4% and the specificity was 71.7% (AUC 0.782; p < 0.001). Conclusions: Few studies in the Mediterranean population have evaluated the role of HbA1c in predicting neonatal complications in women with GDM. A third trimester HbA1c > 5.4% was found to have good sensitivity and specificity for identifying the risk of LGA.

Third trimester HbA1c and the association with large-for-gestational-age neonates in women with gestational diabetes.

OBJECTIVE: To evaluate the association between HbA1c levels measured in the third trimester and the risk for large for gestational age (LGA) in neonates of mothers affected by gestational diabetes mellitus (GDM). Secondarily, we aimed to identify an ideal cut-off for increased risk of LGA amongst pregnant women with GDM. METHODS: Observational retrospective review of singleton pregnant women with GDM evaluated in a diabetes and pregnancy clinic of a tertiary and academic hospital. From January/2011 to December/2017, 1,085 pregnant women underwent evaluation due to GDM, of which 665 had an HbA1c test in the third trimester. A logistic regression model was performed to evaluate predictors of LGA. A receiver-operating-characteristic (ROC) curve was used to evaluate the predictive ability of third trimester HbA1c for LGA identification. RESULTS: A total of 1,085 singleton pregnant women were evaluated during the study period, with a mean age of 32.9 ± 5.3 years. In the multivariate analysis, OGTT at 0 minutes (OR: 1.040; CI 95% 1.006-1.076, p = 0.022) and third trimester HbA1c (OR: 4.680; CI 95% 1.210-18.107, p = 0.025) were associated with LGA newborns. Using a ROC curve to evaluate the predictive ability of third trimester HbA1c for LGA identification, the optimal HbA1c cut-off point was 5.4% where the sensitivity was 77.4% and the specificity was 71.7% (AUC 0.782; p < 0.001). CONCLUSION: Few studies in the Mediterranean population have evaluated the role of HbA1c in predicting neonatal complications in women with GDM. A third trimester HbA1c > 5.4% was found to have good sensitivity and specificity for identifying the risk of LGA.

Obesity markers in patients with drug allergy and body fat as a predictor.

BACKGROUND: Obesity is a chronic low-grade inflammation state associated with several diseases. OBJECTIVE: To investigate a potential link between drug allergy and obesity, exploring whether the association depends on the type (immediate vs nonimmediate) or the severity of the reaction. METHODS: Anthropometric measurements, bioimpedance, and biochemical analysis, including serum adipokines, were performed in 90 consecutive adult patients studied for suspected drug allergy. Logistic regression models were developed to identify predictors of drug allergy. RESULTS: A total of 84 patients completed the diagnostic workup (78.6% women; mean age 39.58 ± 13.3 years). Drug allergy was confirmed in 39 patients and excluded in 45 (controls). Regarding body mass index, 42.2% had normal weight and 55.3% were overweight/obese. A total of 58% of women and 41% of men fulfilled the criteria for central obesity. Patients with drug allergy exhibited considerably higher body mass index, waist and hip circumferences, waist-hip ratio, fat mass, body fat percentage (BFP), trunk fat mass, leptin levels, and leptin-adiponectin ratio than controls. Similar results were obtained in the subgroup with immediate reactions, compared with the nonimmediate or unknown reactions. The higher the BFP and the number of reactions, the greater the odds of drug allergy (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.01-1.14 and OR, 2.82; 95% CI, 1.31-6.10, respectively). An immediate reaction was also a predictor of drug allergy (OR, 3.81; 95% CI, 1.30-11.14, P = .02), compared with nonimmediate or unknown reactions. In patients with drug allergy, BFP was a predictor of having an immediate reaction (OR, 1.12; 95% CI, 1.02-1.24, P = .02). CONCLUSION: Our study illustrates, for the first time, evidence of a link between obesity and drug allergy, particularly immediate reactions. The BFP emerged as a potential predictor of drug allergy.

Exuberant hypercementosis mimicking cementoblastoma / Hipercementose exuberante simulando cementoblastoma

RESUMEN La hipercementosis se clasifica como una proliferación no neoplásica que implica un depósito excesivo de cemento a lo largo del cemento radicular normal. Presentamos el caso de un paciente masculino de 77 años que acude al dentista por una lesión supurativa en la encía que evoluciona desde hace varios meses. El examen radiográfico mostró una gran área radiopaca involucrando la raíz del diente 46, que estaba completamente rodeada por un área radiolúcida, sugiriendo un cementoblastoma asociado con el proceso infeccioso. El examen histopatológico del diente afectado reveló hipercementosis extensa asociada con inflamación supurativa crónica, además de osteomielitis crónica localizada. Esta presentación es infrecuente y, debido a los hallazgos clínico-patológicos, se propone el término "hipercementitis crónica". Los dentistas, especialmente los patólogos orales y endodoncistas, deben estar tener conocimiento de esta inusual presentación para establecer el diagnóstico correcto.

Immunohistochemical characterization of immune cell infiltration in paediatric and adult Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia commonly affecting children with frequent somatic mutations in MAPK pathway genes including BRAFV600E and MAP2K1. Some studies suggest that LCH cells can recruit and modulate inflammatory cells, which could provide reciprocal survival signals. To characterize the immune profile of infiltrating inflammatory cells, and to clarify their participation in LCH pathogenesis, a detailed immunohistochemical analysis was performed. Fifteen (10 children, 5 adults) LCH cases were assessed through macrophage (CD68 and CD163), mature dendritic cell (mDC; CD83 and CD208), regulatory T cell (Treg; CD4, CD25 and FOXP3) and cytotoxic lymphocyte (CL; CD56, CD57, perforin and granzyme B) immunomarkers. Moreover, lymphocytic and LCH markers were also analysed. All cases were S100, CD1a, CD207 and CD4-positive. Bcl-2 and cyclin D1 expression was observed in 13 of 15 cases. In the immune microenvironment, M2-polarized macrophages and Tregs were the predominant cell populations, followed by significantly (P < .005) smaller levels of mDCs and CLs. Additionally, the number of CD3 + cells was significantly higher than that of CD20 + cells. In the CD3 + cell population, there were a significantly higher number of CD4 + cells than CD8 + cells. While there were no differences when comparing the paediatric and adult populations, FOXP3 + cells were significantly higher in patients with multisystem involvement and treated with chemotherapy, than single-site cases and those without chemotherapy. Our results suggest that M2-polarized macrophages and Treg infiltration can promote LCH development and survival, probably through pro-tumoral, immunosuppressive and/or cytokine-mediated mechanisms. This work highlights the need for further exploration of immune-targeted therapy for LCH.

Prevalence of nutritional deficiencies in bariatric surgery candidates and its effect on metabolic status.

BACKGROUND: Nutritional deficiencies are common among obese individuals and constitute one of the main concerns in the bariatric field. The aim of this study was to investigate nutritional status in bariatric surgery candidates, comparing individuals with and without metabolic syndrome (MetS) and to explore possible associations between nutritional and metabolic status. METHODS: Patients accepted for gastric sleeve surgery between 2010 and 2015 were included and anthropometric and metabolic parameters were recorded before surgery. Univariate and multivariate analyses were applied in order to find possible associations between MetS, nutritional, anthropometric, and metabolic parameters. RESULTS: A total of 330 patients were evaluated (285 females, mean age of 41.88 ± 10.4 years old, mean body mass index 43.91 ± 6.2 kg/m2) and MetS was present in 47% of them. Patients without MetS presented a higher prevalence of folate deficiency (12 vs. 2%, p < 0.001). Male gender, older age, lower magnesium levels, and higher BMI and calcium levels were predictors of a greater number of MetS components. Male gender, a greater number of MetS components, and lower magnesium were predictors of higher homeostatic model assessment for insulin resistance (HOMA-IR). CONCLUSIONS: The rising prevalence of obesity is causing a parallel increase in the use of bariatric surgery. The high occurrence of preoperative nutritional deficiencies can impair metabolic status and contribute to a worse outcome after surgery. Nutritional assessment and improvement before surgery may be crucial to optimize patient status, and future studies should explore the effect of the correction of these deficiencies in the metabolic status of these patients.

Pheochromocytoma Due to TMEM127 Mutation - The Importance of Genetic Testing for Clinical Decision.

Apreviously healthy 53-year-old woman presented with new onset arterial hypertension diagnosed during workup for daily pulsatile bilateral frontal headaches and paroxysmal episodes of fatigue, palpitations and sweating. High urinary metanephrines were detected and an abdominal magnetic resonance image evidenced two nodular bilateral adrenal lesions and a left iliac focal lesion. 18F-FDG-PET/CT (fluorodeoxyglucose-positron emission tomography/computed tomography) scanning revealed mild-to-moderate uptake in both adrenal lesions and mild uptake in the iliac bone, whereas 123I-metaiodobenzylguanide scintigraphy revealed uptake only in the right adrenal. CT-scan confirmed the heterogeneous nodular lesion on the right adrenal gland as suspicious for pheochromocytoma and a non-specific sclerotic lesion in the iliac. A right adrenalectomy was performed with posterior resolution of symptoms and normalisation of urinary metanephrines. Histology confirmed a pheochromocytoma and later a mutation of the TMEM127 gene was detected. The present case highlights the importance of genetic testing for pheochromocytoma in order to better guide the management of these patients.

Apolipoprotein B and non-high-density lipoprotein cholesterol reveal a high atherogenicity in individuals with type 2 diabetes and controlled low-density lipoprotein-cholesterol.

BACKGROUND: Lipid-lowering therapy is guided by Low-density-lipoprotein cholesterol (LDL-c) levels, although the cardiovascular disease (CVD) risk could be better reflected by other lipid parameters. This study aimed at comparing a comprehensive lipid profile between patients with type 2 diabetes mellitus (T2DM) with LDL-c concentration within and above target. METHODS: A comprehensive lipid profile was characterized in 96 T2DM patients. The European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) 2016 and 2019 Guidelines for the Management of Dyslipidemias were used to define LDL-c targets. RESULTS: In this population, only 28.1 and 16.7% of patients had mean LDL-c levels within target, as defined by the 2016 and 2019 guidelines, respectively. Applying the 2016 guidelines criteria, in patients with LDL-c within target, 22, 25 and 44% presented non-high-density lipoprotein cholesterol (non-HDL-c), Apolipoprotein B (ApoB) and oxidized LDL-c levels above the recommended range, respectively, whereas according to the 2019 guidelines criteria, 50, 39 and 44% of the patients with LDL-c within target had elevated high-density lipoprotein cholesterol (HDL-c), ApoB and oxidized LDL-c levels, respectively. LDL-c was strongly correlated with non-HDL-c (r = 0.850), ApoB (r = 0.656) and oxidized LDL-c (r = 0.508). Similarly, there was a strong correlation between non-HDL-c with both ApoB (r = 0.808) and oxidized LDL-c (r = 0.588). CONCLUSIONS: These findings emphasize the limitations of only considering LDL-c concentration for cardiovascular (CV) risk assessment. Targeting only LDL-c could result in missed opportunities for CV risk reduction in T2DM patients. These data suggest that non-HDL-c, ApoB and oxidized LDL-c levels could be considered as an important part of these patients' evaluation allowing for a more accurate estimation of CV risk and hopefully better management of these high-risk patients.

Pituitary apoplexy induced by gonadotropin-releasing hormone agonist administration: a rare complication of prostate cancer treatment.

SUMMARY: Gonadotropin-releasing hormone (GnRH) agonists, currently used in the treatment of advanced prostate cancer, have been described as a rare cause of pituitary apoplexy, a potentially life-threatening clinical condition. We report the case of a 69-year-old man with a known pituitary macroadenoma who was diagnosed with prostate cancer and started treatment with GnRH agonist leuprorelin (other hormones were not tested before treatment). Few minutes after drug administration, the patient presented with acute-onset severe headache, followed by left eye ptosis, diplopia and vomiting. Pituitary MRI revealed tumor enlargement and T1-hyperintense signal, compatible with recent bleeding sellar content. Laboratory endocrine workup was significant for low total testosterone. The patient was managed conservatively with high-dose steroids, and symptoms significantly improved. This case describes a rare phenomenon, pituitary apoplexy induced by GnRH agonist. We review the literature regarding this condition: the pathophysiological mechanism involved is not clearly established and several hypotheses have been proposed. Although uncommon, healthcare professionals and patients should be aware of this complication and recognize the signs, preventing a delay in diagnosis and treatment. LEARNING POINTS: Pituitary apoplexy (PA) is a potentially life-threatening complication that can be caused by gonadotropin-releasing hormone agonist (GnRHa) administration for the treatment of advanced prostate cancer. This complication is rare but should be taken into account when using GnRHa, particularly in the setting of a known pre-existing pituitary adenoma. PA presents with classic clinical signs and symptoms that should be promptly recognized. Patients should be instructed to seek medical care if suspicious symptoms occur. Healthcare professionals should be aware of this complication, enabling its early recognition, adequate treatment and favorable outcome.