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Our objective was to analyze the prevalence of lymph node metastasis in early-stage ovarian carcinoma after systematic lymph node dissection and its impact on indication of adjuvant chemotherapy.We evaluated a series of 765 patients diagnosed with ovarian carcinoma who underwent surgical treatment from February 2007 to December 2019. Patients with peritoneal disease and incomplete surgical staging were excluded. All cases underwent systematic pelvic and para-aortic lymphadenectomy up to the renal vessels.A total of 142 cases were analyzed. Median pelvic and para-aortic lymph node dissected were 30 (range, 6-81) and 21 (range, 3-86), respectively. Twelve (8.4%) patients had metastatic lymph nodes - high-grade serous, 10.4% (5/48); clear cell, 17.2% (5/29) and endometrioid, 5.7% (2/35). Any other histology (low grade serous, mucinous, carcinosarcoma or mixed) had lymph node metastasis. Notably, 50% of patients with positive lymph nodes had preoperative suspicious lymph nodes in imaging. The median hospital stay length was 6 days (range, 2-33) and 4.2% cases had grade ≥ 3 complications. A total of 110 (77.6%) patients underwent adjuvant chemotherapy and all cases had indication of adjuvant chemotherapy after histological type, despite the lymph node status. After a median follow-up of 52.5 months, we noted 24 (16.9%) recurrences. The 5-year recurrence-free survival and overall survival were 86.4% and 98.1%, respectively. High grade histology was the only variable that negatively impacted disease-free survival in univariate analysis [HR 4.70 (95%CI: 1.09-20); p = 0.037].We found a positive lymph node rate of less than 10% after lymphadenectomy in presumed early-stage ovarian carcinoma. Lymph node status was not determinant for adjuvant chemotherapy.

Psychosis presentation can be affected by genetic and environmental factors. Differentiating between affective and non-affective psychosis (A-FEP and NA-FEP, respectively) may influence treatment decisions and clinical outcomes. The objective of this paper is to examine differences between patients with A-FEP or NA-FEP in a Latin American sample.Patients from two cohorts of patients with a FEP recruited from Brazil and Chile. Subjects included were aged between 15 and 30 years, with an A-FEP or NA-FEP (schizophrenia-spectrum disorders) according to DSM-IV-TR. Sociodemographic data, duration of untreated psychosis and psychotic/mood symptoms were assessed. Generalized estimating equation models were used to assess clinical changes between baseline-follow-up according to diagnosis status.A total of 265 subjects were included. Most of the subjects were male (70.9 %), mean age was 21.36 years. A-FEP and NA-FEP groups were similar in almost all sociodemographic variables, but A-FEP patients had a higher probability of being female. At baseline, the A-FEP group had more manic symptoms and a steeper reduction in manic symptoms scores during the follow- up. The NA-FEP group had more negative symptoms at baseline and a higher improvement during follow-up. All domains of The Positive and Negative Syndrome Scale improved for both groups. No difference for DUP and depression z-scores at baseline and follow-up.The sample was recruited at tertiary hospitals, which may bias the sample towards more severe cases.This is the largest cohort comparing A-FEP and NA-FEP in Latin America. We found that features in FEP patients could be used to improve diagnosis and support treatment decisions.

To analyze the expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in somatotropinomas specimens and compare clinical, biochemical, radiological, therapeutic, molecular, and pathological data among those who overexpressed (GIPR +) and those who did not overexpress (GIPR - ) GIPR.Clinical, biochemical, radiological, molecular, and pathological data were collected. GNAS1 sequencing was performed with the Sanger method. Protein expression of somatostatin receptor subtypes 2 and 5 and CAM 5.2 were analyzed by immunohistochemistry. Quantitative real-time PCR was performed to analyze the mRNA expression of GIPR with the TaqMan® method. Positive expression was considered when the fold change (FC) was above 17.2 (GIPR +).A total of 74 patients (54% female) were included. Eighteen tumors (24%) were GIPR + . Gsp mutation was detected in 30 tumors (40%). GIPR + tumors were more frequently densely granulated adenomas (83% vs 47%, p = 0.028). There was no difference in clinical, biochemical, radiological, therapeutic (surgical cure or response to medical therapy), or other pathological features between GIPR + and GIPR - tumors. Twenty-eight out of 56 (50%) GIPR - tumors harbored a gsp mutation, whereas two out of 18 (11%) GIPR + tumors harbored a gsp mutation (p = 0.005).We described, for the first time, that GIPR + and gsp mutations are not mutually exclusive, but gsp mutations are less common in GIPR + tumors. GIPR + and GIPR - tumors have similar clinical, biochemical, radiological, therapeutic, and pathological features, with the exception of a high frequency of densely granulated adenomas among GIPR + tumors.

Parkinson's disease (PD) patients may be categorized into tremor-dominant (TD) and postural-instability and gait disorder (PIGD) motor phenotypes, but the dynamical aspects of subthalamic nucleus local field potentials (STN-LFP) and the neural correlates of this phenotypical classification remain unclear.35 STN-LFP (20 PIGD and 15 TD) were investigated through continuous wavelet transform and machine-learning-based methods. The beta oscillation - the main band associated with motor impairment in PD - dynamics was characterized through beta burst parameters across phenotypes and burst intervals under specific proposed criteria for optimal burst threshold definition.Low-frequency (13-22 Hz) beta burst probability was the best predictor for PD phenotypes (75% accuracy). PIGD patients presented higher average burst duration (p = 0.018), while TD patients exhibited higher burst probability (p = 0.014). Categorization into shorter and longer than 400 ms bursts led to significant interaction between burst length categories and the phenotypes (p 0.050) as revealed by mixed-effects models. Long burst durations and short bursts probability positively correlated, respectively, with rigidity-bradykinesia (p = 0.029) and tremor (p = 0.038) scores.Subthalamic low-frequency beta bursts differed between TD and PIGD phenotypes and correlated with motor symptoms.These findings improve the PD phenotypes' electrophysiological characterization and may define new criteria for adaptive deep brain stimulation.

Objectives To evaluate how telomere length behaves in adamantinomtous craniopharyngioma (aCP) and if it contributes to the pathogenesis of aCPs with and without CTNNB1 mutations. Design Retrospective cross-sectional study enrolling 42 aCP patients from 2 tertiary institutions. Methods Clinicopathological features were retrieved from the patient's charts. Fresh frozen tumors were used for RNA and DNA analyses. Telomere length was evaluated by qPCR (T/S ratio). Somatic mutations in TERT promoter (TERTp) and CTNNB1 were detected by Sanger and/or whole-exome sequencing. We performed RNA-Seq to identify differentially expressed genes in aCPs presenting with shorter or longer telomere lengths. Results Mutations in CTNNB1 were detected in 29 (69%) tumors. There was higher frequency of CTNNB1 mutations in aCPs from patients diagnosed under the age of 15 years (85% vs 15%; P = 0.04) and a trend to recurrent disease (76% vs 24%; P = 0.1). No mutation was detected in the TERTp region. The telomeres were shorter in CTNNB1-mutated aCPs (0.441, IQR: 0.297–0.597vs 0.607, IQR: 0.445–0.778; P = 0.04), but it was neither associated with clinicopathological features nor with recurrence. RNAseq identified a total of 387 differentially expressed genes, generating two clusters, being one enriched for short telomeres and CTNNB1-mutated aCPs. Conclusions CTNNB1 mutations are more frequent in children and adolescents and appear to associate with progressive disease. CTNNB1-mutated aCPs have shorter telomeres, demonstrating a relationship between the Wnt/β-catenin pathway and telomere biology in the pathogenesis of aCPs.

Introduction: Radiological indicators in head computed tomography (CT) scan have emerged as tools to evaluate sarcopenia using the sectional area and thickness of the temporal muscle. They can be obtained by standardized measurements in preoperative image assessment of patients with brain aneurysms. We aimed to evaluate the association between functional outcomes after interventions for intracranial aneurysms (IAs) and temporal muscle thickness (TMT) and area (TMA), as surrogates of sarcopenia. Methods: This is a prospective observational cohort study in patients who underwent microsurgery or embolization for ruptured or unruptured IA between January 2018 and December 2019, with a 6-month follow-up. Preoperative CT scans were analyzed to measure TMT and TMA. The functional outcome was assessed by the modified Rankin Scale (mRS). The main outcome was the relationship between sarcopenia and the postoperative functional outcome. Results: A total of 361 patients were included, of whom 199 (55.1%) had ruptured and 162 (44.9%) had unruptured lesions. Larger TMA significantly predicted better functional outcomes at discharge. TMT was associated with functional outcomes at both discharge and 6 months, adjusted for rupture and hypertension. Maximizing the sum sensitivity-specificity, an optimal TMT cutoff of 6.25 mm can predict unfavorable outcomes. Maximizing the positive predictive value × negative predictive value of a product, the cutpoint was 3.55 mm. Conclusions: Sarcopenia, represented by TMT and TMA, is associated with poorer functional results at discharge and 6-month follow-up in IA surgery. TMT below 6.25 mm was associated with unfavorable functional outcomes. These easily obtainable measurements may improve the decision-making process for patients with IAs.

Temporary arterial occlusion (TAO) is a technique widely used in cerebrovascular surgery. However, few studies have evaluated the independent long-term effects of TAO or given detailed information about the complications during in-hospital stay.This study aims to investigate the independent impact of TAO during unruptured intracranial aneurysm surgery on short and long-term outcomes.The study included surgical elective patients diagnosed with unruptured aneurysm and indication of microsurgical treatment. Outcome assessment included occurrence of intra-operative (IOC) and post-operative (POC) complications, as well as Glasgow Outcome Scale (GOS) score 6 months after discharge.114 patients were included and 36 were followed. TAO was associated with POC (OR = 2.08; CI 95% 1.12-3.96; p = 0.01). The group with TAO and intraoperative rupture (IOR) did not differ from the group with TAO without IOR in terms of POC (p = 0.65) and IOC (p = 0.78). IOR (p = 0.16) and number of occlusions (p = 0.23) did not change GOS, but the total time of occlusion was associated with neurologic worsening (p = 0.034) during follow-up. The TAO group had larger aneurysm size and higher frequency of irregular lesions, when compared to the entire study group. Aneurysm location was not associated with POC (p = 0.25), IOC (0.17) or GOS (p = 0.75).The location of temporary clip placement and the number of clips did not influence the short- and long-term outcomes of patients with unruptured intracranial aneurysms. However, presence of temporary clips was associated with POC regardless of IOR occurrence and increased total time of occlusion was associated with poor outcomes after 6 months.

Background Dimensional approaches can decompose a construct in a set of continuous variables, improving the characterization of complex phenotypes, such as schizophrenia. However, the five-factor model of the Positive and Negative Syndrome Scale (PANSS), the most used instrument in schizophrenia research, yielded poor fits in most confirmatory factor analysis (CFA) studies, raising concerns about its applications. Thus, we aimed to identify dimensional PANSS CFA models with good psychometric properties by comparing the traditional CFA with three methodological approaches: Bayesian CFA, multilevel modeling, and Multiple Indicators Multiple Causes (MIMIC) modeling. Methods Clinical data of 700 schizophrenia patients from four centers were analyzed. We first performed a traditional CFA. Next, we tested the three techniques: 1) a Bayesian CFA; 2) a multilevel analysis using the centers as level; and 3) a MIMIC modeling to evaluate the impact of clinical staging on PANSS factors and items. Results CFA and Bayesian CFA produced poor fit models. However, when adding a multilevel structure to the CFA model, a good fit model emerged. MIMIC modeling yielded significant differences in the factor structure between the clinical stages of schizophrenia. Sex, age, age of onset, and duration of illness did not significantly affect the model fit. Conclusion Our comparison of different CFA methods highlights the need for multilevel structure to achieve a good fit model and the potential utility of staging models (rather than the duration of illness) to deal with clinical heterogeneity in schizophrenia. Large prospective samples with biological data should help to understand the interplay between psychometrics concerns and neurobiology research.

To compare the area of exposure to the cisternal thalamus associated with four surgical techniques: supracerebellar-infratentorial (SCIT), occipital interhemispheric (OI), transchoroidal (TC) and subtemporal before and after parahippocampal resection (ST and STh, respectively).All approaches were performed on both sides of three heads. Qualitative anatomical analyses were performed to understand anatomical limits, advantages, and flaws of each technique. Quantitative analyses for multiple repeated dependent variables assessed significant differences between areas of exposure.Exposure area was significantly more extensive using TC and STh approaches compared to ST, OI, and SCIT. STh achieved a significantly wider exposure compared to ST. Regarding dissection angle, surrounding structures and limitations, ST approaches do not provide adequate exposure, nor alignment with the thalamic axis. The OI and STh may provide a better field of exposure, but without adequate alignment and challenging deeper dissections. TC provides better exposure of the cisternal pulvinar with access to lateral pulvinar at the atrium's anterior wall but is a transcortical route that disrupts non-pathological tissue. SCIT provides an adequate area of exposure with the possibility of alignment with the thalamus axis, thus allowing an easier dissection of deeper lesions.For lesions at the pulvinar surface, OI and STh are adequate. For lesions restricted to medial pulvinar and deep along the thalamus axis, SCIT approaches are recommended. Lesions extending to the lateral pulvinar and ventricular atrium are best removed through TC approaches. The ST approach was not suitable to the cisternal pulvinar due to its limited angular exposure.

Context Cushing disease, a chronic hypercortisolism disorder, is associated with considerable morbidity and mortality. Normalizing cortisol production is the primary treatment goal. Objective We aimed to evaluate the safety and efficacy of osilodrostat, a potent, orally available 11βhydroxylase inhibitor, compared with placebo in patients with Cushing disease. Methods LINC 4 was a phase III, multicenter trial comprising an initial 12-week, randomized, double-blind, placebo-controlled (osilodrostat:placebo, 2:1) period followed by a 36-week, open-label treatment period (NCT02697734). Adult patients (aged 18-75 years) with confirmed Cushing disease and mean urinary free cortisol (mUFC) excretion ≥ 1.3 times the upper limit of normal (ULN) were eligible. The primary endpoint was the proportion of randomized patients with mUFC ≤ ULN at week 12. The key secondary endpoint was the proportion achieving mUFC ≤ ULN at week 36 (after 24 weeks’ open-label osilodrostat). Results Seventy-three patients (median age, 39 years [range, 19-67]; mean/median mUFC, 3.1 × ULN/2.5 × ULN) received randomized treatment with osilodrostat (n = 48) or placebo (n = 25). At week 12, significantly more osilodrostat (77%) than placebo (8%) patients achieved mUFC ≤ ULN (odds ratio 43.4; 95% CI 7.1, 343.2; P Conclusion Osilodrostat rapidly normalized mUFC excretion in most patients with Cushing disease and maintained this effect throughout the study. The safety profile was favorable.

ObjectiveTo evaluate the prognostic impact of clinical and pathological variables and patterns of recurrence in patients with locally advanced cervical cancer with pelvic lymph node involvement (stage IIIC1 according to the 2018 FIGO Staging System).MethodsWe retrospectively analyzed 62 patients with locally advanced cervical cancer treated with curative intent with radiotherapy associated with chemotherapy in AC Camargo Cancer Center from January 2007 to December 2018.ResultsLymph node involvement was assessed by CT, MRI and positron emission tomography (PET)/CT in 28 (45.2%), 20 (32.3%) and 14 (22.6%) patients, respectively. The median tumor size was 5.0 cm and 72.6% of cases were squamous cell carcinomas. The median number of positive pelvic lymph nodes was three, and the median size of lymph nodes was 24 mm. Twenty-two (35.5%) patients had recurrence and 50% had only one site of recurrence. The sites of recurrence were pelvic, para-aortic and distant in 12 (19.4%), 6 (9.7%) and 16 (25.8%) patients, respectively. The 3 year overall and disease-free survival were 70.8% and 64.6%, respectively. Patients with adenocarcinoma had worse disease-free survival (HR 2.38; 95% CI 1.01 to 5.60; p=0.047) and overall survival (HR 2.99; 95% CI 1.14 to 7.75; p=0.025) compared with squamous cell carcinoma. In multivariate analysis, metastatic pelvic lymph node size of >2.5 cm (HR 4.38; 95% CI 1.65 to 11.6; p=0.003) and incomplete response to radiotherapy (HR 5.14; 95% CI 1.60 to 16.4; p=0.006) maintained the negative impact for overall survival.ConclusionsWe found that pelvic lymph node size and incomplete response to radiotherapy negatively impact overall survival in patients with advanced cervical cancer with pelvic lymph node involvement. This finding may help to stratify risk in this group of patients.

The European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010-241909 (EUGEI); The Spanish sample was supported by the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024) (...), Velthorst, E., Mollon, J., Murray, R.M., de Haan, L., Germeys, I.M., Glahn, D.C., Arango, C., van der Ven, E., Di Forti, M., Bernardo, M., Guloksuz, S., Delespaul, P., Mezquida, G., Amoretti, S., Bobes, J., Saiz, P.A., García-Portilla, M.P., Santos, J.L., Jiménez-López, E., Sanjuan, J., Aguilar, E.J., Arrojo, M., Carracedo, A., López, G., González-Peñas, J., Parellada, M., Atbaşoğlu, C., Saka, M.C., Üçok, A., Alptekin, K., Akdede, B., Binbay, T., Altınyazar, V., Ulaş, H., Yalınçetin, B., Gümüş-Akay, G., Beyaz, B.C., Soygür, H., Cankurtaran, E.Ş., Kaymak, S.U., Maric, N.P., Mihaljevic, M.M., Petrovic, S.A., Mirjanic, T., Del-Ben, C.M., Ferraro, L., Gayer-Anderson, C., Jones, P.B., Jongsma, H.E., Kirkbride, J.B., La Cascia, C., Lasalvia, A., Tosato, S., Llorca, P.-M., Menezes, P.R., Morgan, C., Quattrone, D., Menchetti, M., Selten, J.-P., Szöke, A., Tarricone, I., Tortelli, A., McGuire, P., Valmaggia, L., Kempton, M.J., van der Gaag, M., Riecher-Rössler, A., Bressan, R.A., Barrantes-Vidal, N., Nelson, B., McGorry, P., Pantelis, C., Krebs, M.-O., Ruhrmann, S., Sachs, G., Rutten, B.P.F., van Os, J., Alizadeh, B.Z., van Amelsvoort, T., Bartels-Velthuis, A.A., Bruggeman, R., van Beveren, N.J., Luykx, J.J., Cahn, W., Simons, C.J.P., Kahn, R.S., Schirmbeck, F., van Winkel, R., Calem, M., Tognin, S., Modinos, G., Pisani, S., Kraan, T.C., van Dam, D.S., Burger, N., Amminger, G.P., Politis, A., Goodall, J., Borgwardt, S., Studerus, E., Gadelha, A., Brietzke, E., Asevedo, G., Asevedo, E., Zugman, A., Domínguez-Martínez, T., Monsonet, M., Cristóbal-Narváez, P., Racioppi, A., Kwapil, T.R., Kazes, M., Daban, C., Bourgin, J., Gay, O., Mam-Lam-Fook, C., Nordholm, D., Rander, L., Krakauer, K., Glenthøj, L.B., Glenthøj, B., Gebhard, D., Arnhold, J., Klosterkötter, J., Lasser, I., Winklbaur, B., Reichenberg, A., EU-GEI High Risk Study

Background The high prevalence of obsessive-compulsive symptoms (OCS) among subjects at Ultra-High Risk (UHR) for psychosis is well documented. However, the network structure spanning the relations between OCS and symptoms of the at risk mental state for psychosis as assessed with the Comprehensive Assessment of At Risk Mental States (CAARMS) has not yet been investigated. This article aimed to use a network approach to investigate the associations between OCS and CAARMS symptoms in a large sample of individuals with different levels of risk for psychosis. Method Three hundred and forty-one UHR and 66 healthy participants were included, who participated in the EU-GEI study. Data analysis consisted of constructing a network of CAARMS symptoms, investigating central items in the network, and identifying the shortest pathways between OCS and positive symptoms. Results Strong associations between OCS and anxiety, social isolation and blunted affect were identified. Depression was the most central symptom in terms of the number of connections, and anxiety was a key item in bridging OCS to other symptoms. Shortest paths between OCS and positive symptoms revealed that unusual thought content and perceptual abnormalities were connected mainly via anxiety, while disorganized speech was connected via blunted affect and cognitive change. Conclusions Findings provide valuable insight into the central role of depression and the potential connective component of anxiety between OCS and other symptoms of the network. Interventions specifically aimed to reduce affective symptoms might be crucial for the development and prospective course of symptom co-occurrence.

Background Lesbian, Gay, Bisexual, Transgender, Queer, and Asexual (LGBTQA+) youth have a greater chance of experiencing stressful life events when compared to cisgender heterosexual peers, which can lead to mental health problems. We aimed to estimate the prevalence of mental disorders among LGBTQA+ youths from two large cities in Brazil. Methods Participants were 13–22 years old youths from the 3rd wave of the Brazilian High-Risk Cohort for Psychiatric Disorders (n = 1475). Mental disorders were assessed using the Development and Well-Being Behavior Assessment. Sexual orientation and gender identity were assessed using a self-report confidential questionnaire. Data were analyzed through logistic regressions (adjusting for sociodemographic) using sampling weights to account for attrition and our oversampling high-risk design. Results 15.18% of the sample described themselves as LGBTQA+. The LGBTQA+ group presented higher rates of anxiety disorders (30.14% vs. 13.37%; OR = 3.37; 95%CI:2.51–4.50), depressive disorders (27.75% vs. 15.34%; OR = 2.17; 95%CI:1.60–2.93) and post-traumatic stress disorder (4.98% vs. 2.25%; OR = 4.20; 95%CI:2.24–7.82), if compared with the cisgender heterosexual group. No difference was found for conduct disorders (2.97% vs. 5.21%; OR = 0.82; 95%CI:0.35–1.65) or attention deficit hyperactivity disorder (5.92% vs. 3.28%; OR = 1.56; 95%CI:0.83–2.79). Limitations Although recruitment was performed at 57 schools in the two cities, sampling was non-probabilistic and included only urban areas, which might bias prevalence estimates and group comparisons. Conclusions Our results elucidate the mental health disparities between LGBTQA+ people and cisgender heterosexuals in Brazil. It highlights the need to promote the inclusion of this population in policy formulation and support actions to mitigate the suffering related to sexual orientation and gender identity.

Cystic lesions arising in the sellar region are not uncommon and encompass cystic pituitary adenomas, Rathke cleft cysts, craniopharyngiomas, and arachnoid cysts. Their clinical presentation may be similar, including headache, visual field defects, and anterior pituitary hormone deficits, which makes differential diagnosis challenging. On the other hand, imaging features may indicate certain pathologies. In this approach to the patient, we describe the case of a patient who presented with right temporal hemianopsia and a sellar/suprasellar cystic lesion, which was determined to be Rathke cleft cyst. We discuss the imaging characteristics that may suggest a particular diagnosis between Rathke cleft cyst, cystic pituitary adenoma, craniopharyngioma, and arachnoid cyst and propose a flowchart for aiding in the imaging differential diagnosis.

Opioids are highly addictive potent analgesics and anti-allodynics whose use has dramatically increased in recent decades. The precipitous rise in opioid dependency and opioid use disorder is an important public health challenge given the risks for severely adverse health outcomes. The long-term opioid impact on hypothalamic-pituitary axes is particularly underappreciated among both endocrinologists and primary care physicians. We review the effects of opioids on hypothalamic-pituitary-target gland function and their implications for clinical practice.Experts in hypothalamic-pituitary disorders and opioid pharmacology reviewed recently published literature and considered strategies for diagnosing and managing these opioid-induced endocrine effects.Opioid suppression of hypothalamic-pituitary axes can lead to hypogonadotropic hypogonadism, central adrenal insufficiency, and hyperprolactinemia. These important clinical manifestations are often under-estimated, poorly evaluated, and typically either untreated or not optimally managed. Data on biochemical testing for diagnosis and on the effect of hormone replacement in these patients is limited and prospective randomized controlled studies for guiding clinical practice are lacking.Patients should be informed about risks for hypogonadism, adrenal insufficiency, and hyperprolactinemia, and encouraged to report associated symptoms. Based on currently available evidence, we recommend clinical and biochemical evaluation for potential central adrenal insufficiency, central hypogonadism, and/or hyperprolactinemia in patients chronically treated with opioids as well as the use of current expert guidelines for the diagnosis and treatment of these conditions.

Introduction Non-functioning pituitary adenomas (NFPAs) are clinically silent tumors and the second most common pituitary adenoma. Surgery is the mainstay of treatment as there is, as yet, no effective medical treatment. Areas covered We present current knowledge on the clinical diagnosis, histopathological classification, molecular data, and management strategies in NFPA. Expert opinion NFPA is a heterogeneous group of tumors, in respect to their origin and clinical course. In recent years, research on pathology and molecular biology have advanced our knowledge of NFPA pathogenesis. NFPA exhibit, in the majority of cases, an indolent behavior, with satisfactory response to treatment. In aggressive cases, multimodal management is needed; however, even this approach may be insufficient, so the development of new treatments is warranted for better management. In this setting, the understanding of the mechanisms involved in the genesis and progression of NFPA is crucial for the identification and development of directed treatments with higher chances of response.

Background Brain magnetic resonance imaging studies have not investigated the cortical surface comprehensively in schizophrenia subjects by assessing thickness, surface area and gyrification separately during the first-episode of psychosis (FEP) or chronic schizophrenia (ChSch). Methods We investigated cortical surface abnormalities in 137 FEP patients and 240 ChSch subjects compared to 297 Healthy Controls (HC) contributed by five cohorts. Maps showing results of vertexwise between-group comparisons of cortical thickness, area, and gyrification were produced using T1-weighted datasets processed using FreeSurfer 5.3, followed by validated quality control protocols. Results FEP subjects showed large clusters of increased area and gyrification relative to HC in prefrontal and insuli cortices (Cohen's d: 0.049 to 0.28). These between-group differences occurred partially beyond the effect of sample. ChSch subjects displayed reduced cortical thickness relative to HC in smaller fronto-temporal foci (d: −0.73 to −0.35), but not beyond the effect of sample. Differences between FEP and HC subjects were associated with male gender, younger age, and earlier illness onset, while differences between ChSch and HC were associated with treatment-resistance and first-generation antipsychotic (FGA) intake independently of sample effect. Conclusions Separate assessments of FEP and ChSch revealed abnormalities that differed in regional distribution, phenotypes affected and effect size. In FEP, associations of greater cortical area and gyrification abnormalities with earlier age of onset suggest an origin on anomalous neurodevelopment, while thickness reductions in ChSch are at least partially explained by treatment-resistance and FGA intake. Associations of between-group differences with clinical variables retained statistical significance beyond the effect of sample.

The aim of this study was to compare the effect of dynamic (DRT) and isometric (IRT) resistance training on glycemic homeostasis, lipid profile, and nitric oxide (NO) in hemodialysis (HD) patients. Patients were randomly distributed into 3 groups: control (n = 65), DRT (n = 65), and IRT (n = 67). Patients assessed before and after the intervention period were tested for fasting blood glucose, glycated hemoglobin, oral glucose tolerance test, insulin resistance, lipid profile, leptin, insulin, adiponectin, C-reactive protein, and NO . Patients underwent to strength and body composition assessments. Subjects allocated in both DRT and IRT groups took part in a 24-week resistance training program, 3 times per week. Each training session was approximately 1 hour before dialysis and consisted of 3 sets of 8–12 repetitions at low intensity. Total workload was higher in the DRT as compared with the IRT. This heightened workload related to better glycemic homeostasis in HD patients as measured by regulation of insulin, adiponectin, and leptin, while improveing triglycerides, free-fat mass, and muscle strength. Additionally, NO levels were increased in the DRT group. NO was significantly correlated with glucose intolerance (r = −0.42, p = 0.0155) and workload (r = 0.46, p = 0.0022). The IRT group only improved strength (p < 0.05). Twenty-four weeks of DRT improved glycemic homeostasis, lipid profile, and NO in HD patients. Although IRT seems to play an important role in increasing strength, DRT might be a better choice to promote metabolic adjustments in HD patients. Clinical trial: http://www.ensaiosclinicos.gov.br/rg/RBR-3gpg5w . Novelty: DRT might be a better choice for metabolic improvements in patients with chronic kidney disease (CKD). Exercise-training might treat metabolic imbalance in CKD patients.

There is compelling evidence showing that between-subject variability in several functional and structural brain features is sufficient for unique identification in adults. However, individuation of brain functional connectomes depends on the stabilization of neurodevelopmental processes during childhood and adolescence. Here, we aimed to (1) evaluate the intra-subject functional connectome stability over time for the whole brain and for large scale functional networks and (2) determine the long-term identification accuracy or 'fingerprinting' for the cortical volumetric profile and the functional connectome. For these purposes, we analysed a longitudinal cohort of 239 children and adolescents scanned in two sessions with an interval of approximately 3 years (age range 6-15 years at baseline and 9-18 years at follow-up). Corroborating previous results using short between-scan intervals in children and adolescents, we observed a moderate identification accuracy (38%) for the whole functional profile. In contrast, identification accuracy using cortical volumetric profile was 95%. Among the large-scale networks, the default-mode (26.8%), the frontoparietal (23.4%) and the dorsal-attention (27.6%) networks were the most discriminative. Our results provide further evidence for a protracted development of specific individual structural and functional connectivity profiles.

Brain-derived neurotrophic factor (BDNF) and the immune-inflammatory response system (IRS) have been implicated in the pathophysiology of schizophrenia. However, no research examined the associations between BDNF and immune activation both before and after treatment in antipsychotic-naïve first episode psychosis (AN-FEP). This study aims to examine serum BDNF levels and their association with IRS and the compensatory immune-regulatory reflex system (CIRS) in AN-FEP before and after risperidone treatment. We included 31 AN-FEP and 22 healthy controls. AN-FEP showed reduced levels of BDNF as compared to controls, and BDNF levels normalized after treatment with risperidone. BDNF levels were inversely correlated with a greater IRS response. Higher levels of IRS/CIRS biomarkers were associated with lower levels of BDNF including M1 macrophage, T-helper (Th)-1, Th-2, and Th-17, and T-regulatory (Treg) cell responses. Our findings indicate that AN-FEP is characterized by decreased levels of BDNF, which are normalized after treatment with risperidone. BDNF levels were inversely associated with activated immune-inflammatory pathways. The findings support the hypothesis that, increased IRS is linked to neurotoxicity, and that a decrease in BDNF may be part of the IRS/CIRS responses in FEP and, thus, be involved in the development of psychosis.

Purpose: To evaluate the risk factors for poor outcomes after surgical and endovascular treatment of aneurysmal subarachnoid hemorrhage (aSAH). Methods: Patients with ≥ 18-years of age and aSAH were included, while patients who died within 12 h of admission or lost follow-up were excluded. All participants underwent standardized clinical and radiological assessment on admission and were reassessed at discharge and at 6-months follow-up using the Glasgow Outcome Scale (GOS). Results: Death at discharge was associated with female gender, anterior communication artery (ACoA) aneurysm location and presence of atherosclerotic plaque in the surgical group, and with age in the endovascular group. Both groups had clinical condition on follow-up associated with mFisher score on admission and hypertension. GOS on follow-up was also associated with presence of atherosclerotic plaque and multiple aneurysms in surgical group, and with age in endovascular group. Conclusions: Subjects treated surgically are prone to unfavorable outcomes if atherosclerotic plaques and multiple aneurysms are present. In patients with endovascular treatment, age was the main predictor of clinical outcome.

IntroductionWith the COVID-19 pandemic, hospitals in low-income countries were faced with a triple challenge. First, a large number of patients required hospitalization because of the infection’s more severe symptoms. Second, there was a lack of systematic and broad testing policies for early identification of cases. Third, there were weaknesses in the integration of information systems, which led to the need to search for available information from the hospital information systems. Accordingly, it is also important to state that relevant aspects of COVID-19’s natural history had not yet been fully clarified. The aim of this research protocol is to present the strategies of a Brazilian network of hospitals to perform systematized data collection on COVID-19 through the World Health Organization (WHO) Platform.Methods and AnalysisThis is a multicenter project among Brazilian hospitals to provide data on COVID-19 through the WHO global platform, which integrates patient care information from different countries. From October 2020 to March 2021, a committee worked on defining a flowchart for this platform, specifying the variables of interest, data extraction standardization and analysis.Ethics and DisseminationThis protocol was approved by the Research Ethics Committee (CEP) of the Research Coordinating Center of Brazil (CEP of the Hospital Nossa Senhora da Conceição), on January 29, 2021, under approval No. 4.515.519 and by the National Research Ethics Commission (CONEP), on February 5, 2021, under approval No. 4.526.456. The project results will be explained in WHO reports and published in international peer-reviewed journals, and summaries will be provided to the funders of the study.Strengths and limitations of this studyAs the study involves a convenience and non-probabilistic sample of patients hospitalized in health units, it may not represent the population of patients with COVID-19 hospitalized in the country. However, the information generated by this research can serve as a basis for the development of maps of the evolution of SARS-CoV-2 infection and public policies to face pandemics. It is a study that uses secondary data, and therefore, information bias may occur, but on the other hand, it has a low cost and facilitates a population-based study with national coverage.Article SummaryThis is a multicenter project among Brazilian hospitals to provide data on COVID-19 through the WHO global platform.It is expected to deepen knowledge about the pandemic scenario and help hospital institutions to develop preventive measures, health service protocols and strengthen the training of teams in the existing complications.

Background The neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte ratio (PLR), and red blood cell distribution width (RDW) have been previously studied as predictors of survival in different malignancies. Objective The aim of this study was to evaluate the predictive value of these hematologic inflammatory biomarkers for patients with brain metastases (BM). Methods We reviewed a consecutive cohort of patients at Instituto do Cancer do Estado de São Paulo (ICESP-FMUSP) from 2011 to 2016 with ≥ 1 BM treated primarily by surgical resection. The primary outcome was 1-year survival. We optimized the NLR, MLR, PLR, and RDW cutoff values, preserving robustness and avoiding overestimation of effect size. Results A total of 200 patients (mean age 56.1 years; 55.0% female) met inclusion criteria. Gross-total resection was achieved in 89.0%. The median (quartiles) preoperative and postoperative KPS scores were 60 (50-80) and 80 (60-90), respectively. Preoperative NLR was significantly associated with survival (HR 2.66, 95% CI: 1.17-6.01, p = 0.019). A NLR cutoff value of 3.83 displayed the most significant survival curve split. Conclusions Preoperative NLR is an independent predictor of survival in newly diagnosed BM. We propose a cutoff value of 3.83 for preoperative NLR testing may be clinically useful as predictor of poor survival in this population. The wide accessibility of the NLR favors its inclusion in clinical decision-making processes for BM management. Resumo Antecedentes Os neutrófilos para linfócitos (NLR), monócitos para linfócitos (MLR), proporção de plaquetas para linfócitos (PLR) e largura de distribuição de glóbulos vermelhos (RDW) foram previamente estudados como preditores de sobrevivência em diferentes malignidades. Objetivo O objetivo deste estudo foi avaliar o valor preditivo desses biomarcadores inflamatórios hematológicos para pacientes com metástases cerebrais (MB). Métodos Nós revisamos uma coorte consecutiva de pacientes no Instituto do Câncer do Estado de São Paulo (ICESP-FMUSP) de 2011 a 2016 com ≥ 1 MB tratados principalmente por ressecção cirúrgica. O desfecho primário foi a sobrevida em 1 ano. Otimizamos os valores de corte de NLR, MLR, PLR e RDW, preservando a robustez e evitando superestimação do tamanho do efeito. Resultados Um total de 200 pacientes (idade média de 56,1 anos; 55,0% mulheres) preencheram os critérios de inclusão. A ressecção grosseira total foi obtida em 89,0%. A mediana (quartis) dos escores KPS pré-operatório e pós-operatório foram 60 (50–80) e 80 (60–90), respectivamente. O NLR pré-operatório foi significativamente associado à sobrevida (HR 2,66, IC 95%: 1,17–6,01, p = 0,019). Um valor de corte de NLR de 3,83 exibiu a divisão da curva de sobrevivência mais significativa. Conclusões O NLR pré-operatório é um preditor independente de sobrevida em MBs recém-diagnosticados. Propomos que um valor de corte de 3,83 para o teste de NLR pré-operatório pode ser clinicamente útil como preditor de baixa sobrevida nesta população. A ampla acessibilidade do NLR favorece sua inclusão nos processos de tomada de decisão clínica para o gerenciamento de BM.

BackgroundThe global burden of persistent COVID-19 in hemodialysis (HD) patients is a worrisome scenario worth of investigation for the critical care of chronic kidney disease (CKD). We performed an exploratory post-hoc study from the trial U1111-1237-8231 with two specific aims: i) to investigate the prevalence of COVID-19 infection and long COVID symptoms from our Cohort of 178 Brazilians HD patients. ii) to identify whether baseline characteristics should predict long COVID in this sample.Methods247 community-dwelling older (>60 years) patients (Men and women) undergoing HD (glomerular filtration rate < 15 mL/min/1.73m2) with arteriovenous fistula volunteered for this study. All patients presented hypertension and diabetes. Patients were divided in two groups: without long-COVID and with long-COVID. Body composition, handgrip strength, functional performance, iron metabolism, phosphate, and inflammatory profile were assessed. Patients were screened for 11-months after COVID-19 infection. Results were considered significant at P < 0.05.ResultsWe found that more than 85% of the COVID-19 infected patients presented a severe condition during the infection. In our sample, the mortality rate over 11-month follow was relatively low (8.4%) when compared to worldwide (approximately 36%). Long COVID was highly prevalent in COVID-19 survivors representing more than 80% of all cases. Phosphate and IL-10 were higher in the long COVID group, but only phosphate higher than 5.35 mg/dL appears to present an increased prevalence of long COVID, dyspnea, and fatigue.ConclusionThere was a high prevalence of COVID-19 infection and long COVID in HD patients from the Brazilian trial ‘U1111-1237-8231’. HD clinics should be aware with phosphate range in HD patients as a possible target for adverse post-COVID events.

BACKGROUND: . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. METHODS: . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/regions, endorsed by national/international professional associations. COH-FIT is a multi-wave, on-line anonymous, cross-sectional survey [wave 1: 04/2020 until the end of the pandemic, 12 months waves 2/3 starting 6/24 months threreafter] for adults, adolescents (14-17), and children (6-13), utilizing non-probability/snowball and representative sampling. COH-FIT aims to identify non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to improve social/health outcomes in the general population/vulnerable subgrous during/after COVID-19. In adults, co-primary outcomes are change from pre-COVID-19 to intra-COVID-19 in well-being (WHO-5) and a composite psychopathology P-Score. Key secondary outcomes are a P-extended score, global mental and physical health. Secondary outcomes include health-service utilization/functioning, treatment adherence, functioning, symptoms/behaviors/emotions, substance use, violence, among others. RESULTS: . Starting 04/26/2020, up to 14/07/2021 >151,000 people from 155 countries/territories/regions and six continents have participated. Representative samples of ≥1,000 adults have been collected in 15 countries. Overall, 43.0% had prior physical disorders, 16.3% had prior mental disorders, 26.5% were health care workers, 8.2% were aged ≥65 years, 19.3% were exposed to someone infected with COVID-19, 76.1% had been in quarantine, and 2.1% had been COVID 19-positive. LIMITATIONS: . Cross-sectional survey, preponderance of non-representative participants. CONCLUSIONS: . Results from COH-FIT will comprehensively quantify the impact of COVID-19, seeking to identify high-risk groups in need for acute and long-term intervention, and inform evidence-based health policies/strategies during this/future pandemics. ispartof: JOURNAL OF AFFECTIVE DISORDERS vol:299 pages:393-407 ispartof: location:Netherlands status: published

BACKGROUND: The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial. METHODS: The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT - www.coh-fit.com) is an on-line anonymous survey, available in 30 languages, involving >230 investigators from 49 countries supported by national/international professional associations. COH-FIT has thee waves (until the pandemic is declared over by the WHO, and 6-18 months plus 24-36 months after its end). In addition to adults, COH-FIT also includes adolescents (age 14-17 years), and children (age 6-13 years), recruited via non-probability/snowball and representative sampling and assessed via self-rating and parental rating. Non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to promote health and prevent mental and physical illness in children and adolescents will be generated by COH-FIT. Co-primary outcomes are changes in well-being (WHO-5) and a composite psychopathology P-Score. Multiple behavioral, family, coping strategy and service utilization factors are also assessed, including functioning and quality of life. RESULTS: Up to June 2021, over 13,000 children and adolescents from 59 countries have participated in the COH-FIT project, with representative samples from eleven countries. LIMITATIONS: Cross-sectional and anonymous design. CONCLUSIONS: Evidence generated by COH-FIT will provide an international estimate of the COVID-19 effect on children's, adolescents' and families', mental and physical health, well-being, functioning and quality of life, informing the formulation of present and future evidence-based interventions and policies to minimize adverse effects of the present and future pandemics on youth. ispartof: JOURNAL OF AFFECTIVE DISORDERS vol:299 pages:367-376 ispartof: location:Netherlands status: published

Correa, HdL, Deus, LA, Neves, RVP, Reis, AL, de Freitas, GS, de Araujo, TB, da Silva Barbosa, JM, Prestes, J, Simoes, HG, Amorim, CE, dos Santos, MAP, Haro, A, de Melo, GF, Gadelha, AB, Neto, LS, and Rosa, TdS. Influence of angiotensin converting enzyme I/D polymorphism on hemodynamic and antioxidant response to long-term intradialytic resistance training in patients with chronic kidney disease: a randomized controlled trial. J Strength Cond Res 35(10): 2902-2909, 2021-The aim of the study was to verify the influence of Angiotensin-converting enzyme (ACE) I/D genotype on blood pressure, muscle mass, and redox balance response to long-term resistance training (RT) in end-stage renal disease patients. Three hundred and twenty subjects were randomized into 4 groups: II + ID control (II + ID CTL, n = 80), II + ID RT (II + ID RT, n = 79), DD control (DD CTL n = 83), and DD RT (DD RT, n = 78). The RT lasted 24 weeks with a frequency of 3 times per week, on alternative days. Each section consisted of 3 sets of 8-12 repetitions in 11 exercises, with training loads at 6 point (somewhat hard) to 8 point (hard) based on OMNI-RES scale and was prescribed during dialysis (intradialytic). Statistical significance was accepted with p < 0.05. The most relevant benefits in blood pressure were found for DD homozygotes (p < 0.0001), whereas allele I carriers displayed a higher increase in muscle mass (p < 0.0001). Hemodialysis clinics that already use RT for their patients could include the genotyping of ACE to identify the predisposal of the patients to respond to RT and to counteract kidney disease-related comorbidities.

AIM Construct stability over time is required for reliable inference, but evidence regarding the longitudinal invariance of negative symptoms is still limited. Thus, we examined the longitudinal invariance of the negative dimension using the positive and negative syndrome scale (PANSS) in an antipsychotic-naive first-episode schizophrenia sample at baseline and after 10 weeks. METHODS Our study was conducted at a specialized early intervention service. PANSS ratings were analysed for 138 patients, and two different models were specified and tested: a unidimensional and a two-correlated factor solution. RESULTS The unidimensional model fulfilled criteria for longitudinal invariance, whilst the two-correlated did not. CONCLUSION Our study provides support for the PANSS negative unidimensional model use to evaluate negative symptoms' longitudinal change following first-episode schizophrenia.

Hepatitis B virus (HBV) infection is a concern for public health due to its high prevalence, high infectivity, morbidity, and mortality worldwide. Brazil presents a low HBV prevalence, but has considerable heterogeneity among its geographic regions. Here, we describe the epidemiological profile of HBV infection in different regions of Brazil during 2007–2018, as well as the historical trends associated with the infection. We conducted an observational, ecological time-series study using secondary data collected from the National Notifiable Diseases Information System (SINAN). Our findings suggest that HBV infection was more likely to occur in young, sexually active adults. Individuals from Northeast and Midwest regions were more likely to present acute HBV infection, while individuals from South region were more likely to present chronic HBV infection, reinforcing that specific strategies are required for each particular region. Additionally, we observed a general decreasing trend of infection starting in 2014, however there was an increasing trend of infection in men and in individuals over 40 years old. Although we observed a decreasing trend in HBV infection, active surveillance is needed to prevent HBV spread and possible epidemics, as well as encouraging the vaccination of adults, especially young adult males. Our findings can inform the conduct of large-scale observational studies to evaluate clinical, economical, and social impacts of HBV infections, leading to improved social policies. Finally, our results highlight the need to improve data quality and completeness of epidemiological data, minimizing eventual errors that can make prevention and control strategies difficult.

SUMMARY OBJECTIVE: Decompressive craniectomy may be a life-saving measure in ischemic stroke patients, who still have several associated complications. The objective of this study is to evaluate a novel decompressive surgery technique for severe hemispheric ischemic stroke. METHODS: For the hinge decompressive craniectomy (HDC), linear durotomies were performed. Vertical (one or two frontal and two parietal), and two horizontal (temporal), with approximately 5 cm long, linear durotomies were carried out. Duroplasty was performed using an autologous subgaleal tissue graft fixed with separate sutures to avoid CSF leak and direct contact of the cortex with the bone flap. The bone flap was fixed in three parietal locations. We compared 10 patients who underwent our modified HDC with 9 patients submitted to classical decompressive craniectomy (CDC). The primary outcome of this study was mortality. RESULTS: Nineteen patients were included, with a mean age of 52.3 years (±8.2). Four (44%) patients from the HDC group had to be reoperated to remove the bone flap because of brain swelling worsening, but none of them died. The average time of HDC was 90 minutes. Overall 14-days mortality was 21.1% (n=4), and cumulative six-months mortality was 42.1% (n=8). Five (50%) patients submitted to CDC died, while 3 (33.3%) submitted to HDC died (χ2=0.07, p=0.79). The mean length of stay was 46.7 days (±32.1) for HDC and 38.7 (±27.1) for CDC (p=0.60). CONCLUSIONS: We present a modified technique of hinge craniectomy with linear vertical and horizontal durotomies, which seems to have reduced operative time and mortality compared to classical decompressive craniotomy, although the difference was not statistically significant.

COVID-19, the illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus belonging to the Coronaviridade family, a single-strand positive-sense RNA genome, has been spreading around the world and has been declared a pandemic by the World Health Organization. On 17 January 2022, there were more than 329 million cases, with more than 5.5 million deaths. Although COVID-19 has a low mortality rate, its high capacities for contamination, spread, and mutation worry the authorities, especially after the emergence of the Omicron variant, which has a high transmission capacity and can more easily contaminate even vaccinated people. Such outbreaks require elucidation of the taxonomic classification and origin of the virus (SARS-CoV-2) from the genomic sequence for strategic planning, containment, and treatment of the disease. Thus, this work proposes a high-accuracy technique to classify viruses and other organisms from a genome sequence using a deep learning convolutional neural network (CNN). Unlike the other literature, the proposed approach does not limit the length of the genome sequence. The results show that the novel proposal accurately distinguishes SARS-CoV-2 from the sequences of other viruses. The results were obtained from 1557 instances of SARS-CoV-2 from the National Center for Biotechnology Information (NCBI) and 14,684 different viruses from the Virus-Host DB. As a CNN has several changeable parameters, the tests were performed with forty-eight different architectures; the best of these had an accuracy of 91.94 +/- 2.62% in classifying viruses into their realms correctly, in addition to 100% accuracy in classifying SARS-CoV-2 into its respective realm, Riboviria. For the subsequent classifications (family, genera, and subgenus), this accuracy increased, which shows that the proposed architecture may be viable in the classification of the virus that causes COVID-19., Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), High-Performance Computing Center at UFRN(NPAD/UFRN)

Human spermatozoa must swim through the female reproductive tract, where they undergo a series of biochemical and biophysical reactions called capacitation, a necessary step to fertilize the egg. Capacitation promotes changes in the motility pattern. Historically, a two-dimensional analysis has been used to classify sperm motility and clinical fertilization studies. Nevertheless, in a natural environment sperm motility is three-dimensional (3D). Imaging flagella of freely swimming sperm is a difficult task due to their high beating frequency of up to 25 Hz. Very recent studies have described several sperm flagellum 3D beating features (curvature, torsion, asymmetries, etc.). However, up to date, the 3D motility pattern of hyperactivated spermatozoa has not been characterized. The main difficulty in classifying these patterns in 3D is the lack of a ground truth reference since differences in flagellar beat patterns are very difficult to assess visually. Moreover, only around 10-20% of induced to capacitate spermatozoa are truly capacitated, i.e., hyperactivated. We used an image acquisition system that can acquire, segment, and track spermatozoa flagella in 3D+t. In this work, we propose an original three-dimensional feature vector formed by ellipses describing the envelope of the 3D+t spatio-temporal flagellar sperm motility patterns. These features allowed compressing an unlabeled 3D+t dataset to separate hyperactivated cells from others (capacitated from non-capacitated cells) using unsupervised hierarchical clustering. Preliminary results show three main clusters of flagellar motility patterns. The first principal component of these 3D flagella measurements correlated with 2D OpenCASA head determinations as a first approach to validate the unsupervised classification, showing a reasonable correlation coefficient near to 0.7. Clinical relevance- The novelty of this work is defining a 3D+t feature-based descriptor consisting of a set of ellipses enveloping the flagellar motion of human sperm for its unsu-pervised classification. This is a new promising tool to determine the viability of human sperm to fertilize the egg.

Corticotroph macroadenomas are rare but difficult to manage intracranial neoplasms. Mutations in the two Cushing’s disease mutational hotspots USP8 and USP48 are less frequent in corticotroph macroadenomas and invasive tumors. There is evidence that TP53 mutations are not as rare as previously thought in these tumors. The aim of this study was to determine the prevalence of TP53 mutations in corticotroph tumors, with emphasis on macroadenomas, and their possible association with clinical and tumor characteristics. To this end, the entire TP53 coding region was sequenced in 86 functional corticotroph tumors (61 USP8 wild type; 66 macroadenomas) and the clinical characteristics of patients with TP53 mutant tumors were compared with TP53/USP8 wild type and USP8 mutant tumors. We found pathogenic TP53 variants in 9 corticotroph tumors (all macroadenomas and USP8 wild type). TP53 mutant tumors represented 14% of all functional corticotroph macroadenomas and 24% of all invasive tumors, were significantly larger and invasive, and had higher Ki67 indices and Knosp grades compared to wild type tumors. Patients with TP53 mutant tumors had undergone more therapeutic interventions, including radiation and bilateral adrenalectomy. In conclusion, pathogenic TP53 variants are more frequent than expected, representing a relevant amount of functional corticotroph macroadenomas and invasive tumors. TP53 mutations associated with more aggressive tumor features and difficult to manage disease.

The COVID-19 pandemic has profoundly disrupted health care worldwide. We aimed to evaluate the impact of the first COVID-19 wave on the treatment of our patients with acromegaly.A standard questionnaire was systematically applied to all patients and included questions on general health status, whether all laboratory workup had been done, common signs and symptoms of acromegaly, treatment adherence, and previous COVID-19 symptoms and diagnosis.We attempted to contact 136 patients with acromegaly at regular follow-up at our institution and contacted 101 of them successfully. In all, 37% of the patients reported symptoms of acromegaly, which was more common among women. A total of 27 patients were lost to follow-up (including 19 who interrupted treatment during the pandemic) mainly for fear of becoming infected by the SARS-CoV-2. Of these, 24 resumed follow-up after our contact.The current COVID-19 pandemic has strongly impacted the follow-up of patients with acromegaly. Telemedicine can be an important tool to maintain regular treatment in the current or future pandemics.

To compare biochemical and tumor response rates between two reference centers for pituitary diseases in Brazil after primary and adjuvant therapy with somatostatin receptor ligands (SRL) in acromegaly. Patients were classified as non-responders (NR), partial responders (PR), and full responders (FR) to 12-month SRL therapy according to: [criteria A] normal IGF-I and random GH (rGH)

BACKGROUND: Musculoskeletal disorders in acromegaly compromise upper and lower limb activity. Corresponding changes can be better assessed by a functional capacity test incorporating multitasking, such as the Glittre Activities of Daily Living Test (GA-T). OBJECTIVES: To evaluate functional capacity in adults with acromegaly using the GA-T and to correlate functional capacity with hand function and health-related quality of life. METHODS: The GA-T was applied to 36 patients with acromegaly and an equal number of healthy individuals. Additionally, participants completed the Acromegaly Quality of Life (AcroQoL) questionnaire and underwent a chronic pain assessment using a map of the human body, a hand function evaluation using the Cochin Hand Functional Scale (CHFS), and a handgrip strength test. RESULTS: Relative to the comparison group, patients with acromegaly required more time to perform the GA-T, showed worse hand function, and reported that squatting to accomplish shelving tasks was the major difficulty. GA-T time was correlated with the AcroQoL global score, handgrip strength, and the CHFS (rs=-0.487, p= 0.002; rs=-0.369, p= 0.026; rs= 0.538, p= 0.0007, respectively). CONCLUSIONS: Patients with acromegaly exhibited a reduced functional capacity as assessed by the GA-T. Additionally, an association was identified between the total GA-T time and both hand function and quality of life.

Sarcopenia and chronic kidney disease (CKD) have been associated with negative outcomes in older people, including inflammatory profile and anemia biomarkers. To investigate the effects of pre-dialysis resistance training (RT) on sarcopenia, inflammatory profile, and anemia biomarkers in older patients with CKD. A total of 107 patients with CKD (65.4 ± 3.7 years) were randomly allocated into four groups: sarcopenic RT (n = 37), non-sarcopenic RT (n = 20), sarcopenic control (n = 28), and non-sarcopenic control (n = 22). DXA and handgrip strength were used to classify sarcopenia according to EWGSOP-2. Treatment groups underwent a 24-week intervention with RT before each dialysis session, three times per week. Blood sample analysis for ferritin, hepcidin, iron availability, and inflammatory profile (TNFα, IL-6, and IL-10) was conducted. All-cause mortality was recorded over 5 years. Sarcopenic RT group increased iron availability after the intervention, while their counterparts decreased. Ferritin and hepcidin significantly decreased in sarcopenic RT group. RT elicited a reduction in both TNFα and IL-6, while increasing IL-10 in both intervention groups. The rate of sarcopenic subjects substantially decreased after the intervention period (from 37 to 17 in the RT group; p = 0.01). The proportion of deaths was higher (P = 0.033) for sarcopenic subjects (Controls 35.7% vs RT 29.7%) when compared to non-sarcopenic subjects (Controls 18% vs RT 10%). The proportion of deaths decreased according to the randomization group (X2 = 8.704; P

Objective To analyze the predictive factors for non-sentinel lymph node (non-SLN) metastasis in early-stage cervical cancer. Methods We analyzed a series of 113 patients who underwent sentinel lymph node (SLN) mapping for cervical cancer. The SLNs were examined by immunohistochemistry (IHC) when the hematoxylin-eosin stain was negative. Results The overall bilateral detection rate was 81.5%, with a median of two SLNs resected. The study ultimately included 92 patients with SLNs that were mapped who had also undergone systematic pelvic lymph node dissection. Thirteen (14.1%) patients had positive SLNs, with a median of one positive SLN. Regarding the size of SLN metastasis, one (1.1%) had isolated tumor cells (ITC), seven (7.6%) had micrometastases, and five (5.4%) had macrometastases. Notably, 46.1% (6/13) had lymph node metastases detected only after IHC. Five (38.5%) cases had positive non-SLNs, with a median count of one positive lymph node. Parametrial invasion was the only risk factor for positive non-SLN (p = .045). Regarding the size of SLN metastasis, non-SLN involvement was present in the only case with ITC (1/1), 42.9% (3/7) of cases with micrometastases, and in 20% (1/5) with macrometastases. Conclusions Our data suggest that parametrial invasion correlates with the risk of non-SLN metastasis in cervical cancer.

The extended scope and complexity of the United Nations 2030 agenda entail important challenges for the operationalization of the health-related sustainable development goal (SDG) indicators. Divergences in concepts, agendas and implementation strategies among institutions have fostered the parallel development of alternative and concurrent indicators. We aim to determine the convergences and divergences between five key institutions: the Global Burden of Disease Study (GBD), the Pan American Health Organization, the Sustainable Development Solutions Network, the World Bank and the World Health Organization (WHO). Of the 104 health-related indicators listed by these five institutions, 60 are consistent with official Inter-agency and Expert Group SDG indicators. Our analysis considers the indicators included, and the themes these indicators cover, in each institution list and each institution online platform. We quantified convergence in indicators between the institutions themselves, but also between the institutions and the official Inter-agency and Expert Group. Our results indicate important divergences; only 22 of the 60 indicators are included in the lists of all five institutions. The level of adoption of the official metrics varies from 40.5% (15/(47-10)) for the GBD to 86.2% (25/(29-0)) for the World Bank. WHO, the official curator of the Inter-agency and Expert Group SDG indicators, is only convergent with the official metrics by 72.1% (31/(45-2)). Our analysis, and the resulting awareness of the differences, potentialities and limitations of indicators and platforms, provides important contributions to enable the achievement of the health-related SDGs and deliver the promise of the 2030 agenda.La complexité et l'envergure de l'Agenda 2030 des Nations Unies représentent d'importants défis pour la concrétisation des indicateurs régissant l'objectif de développement durable (ODD) visant à assurer la santé et le bien-être de tous. Les divergences de concepts, de programmes et de stratégies de mise en œuvre au sein des institutions ont engendré l'apparition simultanée d'indicateurs alternatifs et concurrents. Nous cherchons à identifier les convergences et divergences entre cinq institutions clés: l'étude sur la charge mondiale de morbidité (GBD), l'Organisation panaméricaine de la Santé, le Réseau des solutions pour le développement durable, la Banque mondiale et l'Organisation mondiale de la Santé (OMS). Sur les 104 indicateurs de santé repris par ces cinq institutions, 60 sont compatibles avec ceux du Groupe d'experts interinstitutionnel sur les indicateurs des ODD. Notre analyse tient compte des indicateurs inclus, ainsi que des domaines dont ils traitent, dans chaque liste institutionnelle et sur chaque plateforme institutionnelle en ligne. Nous avons quantifié la convergence d'indicateurs entre les institutions elles-mêmes, mais aussi entre ces institutions et le Groupe d'experts interinstitutionnel officiel. Nos résultats révèlent d'importantes divergences; seulement 22 des 60 indicateurs figurent dans les listes des cinq institutions. Le niveau d'adoption des paramètres officiels varie de 40,5% (15/(47–10)) pour le GBD à 86,2% (25/(29–0)) pour la Banque mondiale. L'OMS, administratrice officielle du Groupe d'experts interinstitutionnel sur les indicateurs des ODD, ne s'aligne sur les paramètres officiels qu'à 72,1% (31/(45–2)). Notre analyse et sa mise en évidence des différences, des possibilités et des limites des indicateurs et plateformes, contribue grandement à progresser vers la réalisation des ODD en matière de santé, et vers la concrétisation des promesses de l'Agenda 2030.El amplio alcance y la complejidad del programa de las Naciones Unidas para 2030 implica importantes desafíos para la puesta en práctica de los indicadores del objetivo de desarrollo sostenible (ODS) relacionado con la salud. Las divergencias en los conceptos, los programas y las estrategias de aplicación entre las instituciones han fomentado la elaboración paralela de indicadores alternativos y simultáneos. Nos proponemos determinar las convergencias y divergencias entre cinco instituciones clave: el Estudio sobre la Carga Mundial de la Enfermedad (GBD, por sus siglas en inglés), la Organización Panamericana de la Salud, la Red de Soluciones para el Desarrollo Sostenible, el Banco Mundial y la Organización Mundial de la Salud (OMS). De los 104 indicadores relacionados con la salud enumerados por estas cinco instituciones, 60 son coherentes con los indicadores oficiales del ODS del Grupo Interinstitucional y de Expertos. Nuestro análisis tiene en cuenta los indicadores incluidos, y los temas que cubren estos indicadores, en cada lista de instituciones y en la plataforma en línea de cada institución. Cuantificamos la convergencia en los indicadores entre las propias instituciones, pero también entre las instituciones y el Grupo Interinstitucional y de Expertos oficial. Nuestros resultados indican importantes divergencias; solo 22 de los 60 indicadores están incluidos en las listas de las cinco instituciones. En cuanto al nivel de adopción de los indicadores oficiales varía entre el 40,5% (15/(47-10)) en el caso del GBD y el 86,2% (25/(29-0)) en el caso del Banco Mundial. La OMS, la comisaria oficial de los indicadores del ODS del Grupo Interinstitucional de Expertos, solo converge con los parámetros oficiales en un 72,1% (31/(45-2)). Nuestro análisis, y la consiguiente conciencia de las diferencias, potencialidades y limitaciones de los indicadores y plataformas, aporta importantes contribuciones para permitir el logro de los ODS relacionados con la salud y cumplir con el compromiso del programa de 2030.ينطوي كل من النطاق والسياق الموسعين لخطة الأمم المتحدة لعام 2030 على تحديات هامة لتفعيل مؤشرات أهداف التنمية المستدامة (SDG) المتعلقة بالصحة. وقد أدت الاختلافات في المفاهيم، وجداول الأعمال، واستراتيجيات التنفيذ بين المؤسسات، إلى تعزيز التطوير الموازي للمؤشرات البديلة والمتزامنة. نحن نهدف إلى تحديد أوجه التقارب والاختلاف بين خمس مؤسسات رئيسية: دراسة العبء العالمي للأمراض (GBD)، ومنظمة الصحة للبلدان الأمريكية، وشبكة حلول التنمية المستدامة، والبنك الدولي، ومنظمة الصحة العالمية (WHO). من بين 140 من المؤشرات المتعلقة بالصحة المدرجة في هذه المؤسسات الخمس، هناك 60 مؤشرًا تتسق مع مؤشرات أهداف التنمية المستدامة الرسمية المشتركة بين الوكالات ومجموعة الخبراء. يضع تحليلنا في الاعتبار المؤشرات المضمنة، والموضوعات التي تغطيها هذه المؤشرات، في قائمة كل مؤسسة وكل منصة على الإنترنت لكل مؤسسة. قمنا بقياس التقارب في المؤشرات بين المؤسسات نفسها، ولكن أيضًا بين المؤسسات ومجموعة الخبراء الرسمية المشتركة بين الوكالات. تشير نتائجنا إلى اختلافات مهمة؛ تم تضمين 22 مؤشرًا فقط من بين 60 مؤشرًا في قوائم كل المؤسسات الخمس. يختلف مستوى تطبيق المقاييس الرسمية من 40.5% (15/(47-10)) للعبء العالمي للأمراض إلى 86.2% (25/(29–0)) للبنك الدولي. منظمة الصحة العالمية، التي تمثل المنسق الرسمي لمؤشرات أهداف التنمية المستدامة لمجموعة الخبراء المشتركة بين الوكالات، تتقارب فقط مع المقاييس الرسمية بنسبة 72.1% (31/(45-2)). إن تحليلنا، والوعي الناتج عن اختلافات وإمكانيات وقيود المؤشرات والمنصات، يوفر مساهمات مهمة لتمكين تحقيق أهداف التنمية المستدامة المتعلقة بالصحة والوفاء بوعد أجندة العمل لعام 2030.联合国《2030 年可持续发展议程》的范围不断扩大且复杂度越来越高，这给健康相关可持续发展目标 (SDG) 指标的实现带来了重大挑战。各机构在概念、议程和执行战略方面的差异促使各机构同步制定了替代指标和并行指标。我们旨在确定五个关键机构之间的趋同与分化：全球疾病负担研究 (GBD)、泛美卫生组织、可持续发展解决方案网络、世界银行和世界卫生组织 (WHO)。在这五个机构列出的 104 个健康相关指标中，有 60 个与官方的机构间专家组 SDG 指标一致。我们分析时考虑了各机构列表和各机构在线平台中包含的指标以及这些指标涵盖的主题。我们不仅对上述机构之间的指标趋同度进行量化，还对这些机构与官方机构间专家组间的指标趋同度进行了量化。我们的结果显示存在重大分化；这五个机构的列表仅包括了 60 个指标中的 22 个。官方指标的采纳率从 GBD 的 40.5% (15/(47–10)) 至世界银行的 86.2% (25/(29–0)) 不等。世卫组织是机构间专家组 SDG 指标的官方监管组织，与官方指标的趋同率仅为 72.1% (31/(45–2))。我们的分析以及由此产生的对指标和平台的差异、潜力和局限性的认识，为实现健康相关 SDG 和履行《2030 年可持续发展议程》的承诺做出了重要贡献。.Расширенный охват и сложность повестки дня Организации Объединенных Наций на период до 2030 года влечет за собой серьезные проблемы с практическим внедрением показателей состояния здоровья для целей в области устойчивого развития (ЦУР). Расхождения в концепциях, повестках дня и стратегиях реализации между учреждениями способствовали параллельной разработке альтернативных и параллельных показателей. Авторы стремятся определить совпадения и расхождения между пятью ключевыми учреждениями: исследованием глобального бремени заболеваний (ГБЗ), Панамериканской организацией здравоохранения, сетью решений для обеспечения устойчивого развития, Всемирным банком и Всемирной организацией здравоохранения (ВОЗ). Из 104 показателей состояния здоровья, указанных этими пятью учреждениями, 60 соответствуют официальным показателям межучрежденческой и экспертной группы по показателям достижения целей в области устойчивого развития. В нашем анализе рассматриваются включенные показатели и темы, которые охватывают эти показатели, в списке и на онлайн-платформе каждого учреждения. Авторы выполнили количественную оценку сходства показателей как между самими учреждениями, так и между учреждениями и официальной межучрежденческой и экспертной группой. Наши результаты указывают на важные расхождения. Только 22 из 60 показателей включены в списки всех пяти учреждений. Уровень принятия официальных показателей варьируется от 40,5% (15/(47–10)) для ГБЗ до 86,2% (25/(29–0)) для Всемирного банка. Значения ВОЗ, официального куратора показателей межучрежденческой и экспертной группы по показателям достижения целей в области устойчивого развития, совпадают с официальными показателями лишь на 72,1% (31/(45–2)). Наш анализ и вытекающая из этого осведомленность о различиях, возможностях и ограничениях показателей и платформ вносят важный вклад в достижение ЦУР, связанных со здоровьем, и выполнение обещаний повестки дня на период до 2030 года.

Over the last few years, the role of early postoperative computed tomography (EPOCT) after cranial surgery has been repeatedly questioned, but there is yet no consensus on the practice. We conducted a systematic review to address the usefulness of EPOCT in association with neurological examination after elective craniotomies compared to the neurological examination alone. Studies were eligible if they provided information about the number of patients scanned, how many were asymptomatic or presented neurological deterioration before the scan and how many of each of those groups had their management changed due to imaging findings. CTs had to be performed in the first 48 h following surgery to be considered early. Eight studies were included. The retrospective studies enrolled a total of 3639 patients, with 3737 imaging examinations. Out of the 3696 CT scans performed in asymptomatic patients, less than 0.8% prompted an intervention, while 100% of patients with neurological deterioration were submitted to emergency surgery. Positive predictive values of altered scans were 0.584 for symptomatic patients and 0.125 for the asymptomatic. The number of altered scans necessary to predict (NNP) one change in management for the asymptomatic patients was 8, while for the clinically evident cases, it was 1.71. The number of scans needed to diagnose one clinically silent alteration is 134.75, and postoperative imaging of neurologically intact patients is 132 times less likely to issue an emergency intervention than an altered neurological examination alone. EPOCT following elective craniotomy in neurologically preserved patients is not supported by current evidence, and CT scanning should be performed only in particular conditions. The authors have developed an algorithm to help the judgment of each patient by the surgeon in a resource-limited context.

First-line treatment for Cushing´s disease is transsphenoidal surgery. But in cases of persistent or recurrent disease after surgery, contraindications to surgery, severe hypercortisolism control before surgery, or for patients waiting for radiotherapy effects, medical therapy may be indicated. Pituitary-directed agents include cabergoline and pasireotide. Both drugs present similar potential for biochemical control and pasireotide has additionally been proved to reduce tumor volume. Moreover, pasireotide was evaluated in high quality studies. In respect to safety, both drugs are well tolerated and safe, but special attention should be given for cardiac valve disease and psychiatric disorder for cabergoline, and hyperglycemia for pasireotide.