Association of Emotional Self-Regulation with Psychological Distress and Positive Functioning Dimensions in Brazilian University Students during the COVID-19 Pandemic.

Emotional self-regulation is a relevant factor for human development capable of minimizing emotional difficulties in the face of adverse events, as was particularly useful during the COVID-19 pandemic. The present study aimed to evaluate emotional self-regulation in Brazilian health science university students and its relationship with positive psychology constructs (subjective well-being, hope, optimism, spirituality, self-compassion, and self-efficacy) and psychological distress (depression, anxiety, and stress). This was a prospective, cross-sectional, observational, analytic study of 1062 Brazilian undergraduate students with data collected using self-administered online questionnaires. Students in the first years of their undergraduate degree programs had significantly higher dysregulation scores than those in the final years. Multiple linear regression yielded a model that explained 71.8% of the variation in emotion dysregulation. The correlations of emotion dysregulation were significant and strong, scoring negatively with self-compassion, optimism, and subjective well-being and positively with psychological distress.

Machine Learning-based Prediction Model for Treatment of Acromegaly With First-generation Somatostatin Receptor Ligands.

CONTEXT: Artificial intelligence (AI), in particular machine learning (ML), may be used to deeply analyze biomarkers of response to first-generation somatostatin receptor ligands (fg-SRLs) in the treatment of acromegaly. OBJECTIVE: To develop a prediction model of therapeutic response of acromegaly to fg-SRL. METHODS: Patients with acromegaly not cured by primary surgical treatment and who had adjuvant therapy with fg-SRL for at least 6 months after surgery were included. Patients were considered controlled if they presented growth hormone (GH) <1.0 ng/mL and normal age-adjusted insulin-like growth factor (IGF)-I levels. Six AI models were evaluated: logistic regression, k-nearest neighbor classifier, support vector machine, gradient-boosted classifier, random forest, and multilayer perceptron. The features included in the analysis were age at diagnosis, sex, GH, and IGF-I levels at diagnosis and at pretreatment, somatostatin receptor subtype 2 and 5 (SST2 and SST5) protein expression and cytokeratin granulation pattern (GP). RESULTS: A total of 153 patients were analyzed. Controlled patients were older (P = .002), had lower GH at diagnosis (P = .01), had lower pretreatment GH and IGF-I (P < .001), and more frequently harbored tumors that were densely granulated (P = .014) or highly expressed SST2 (P < .001). The model that performed best was the support vector machine with the features SST2, SST5, GP, sex, age, and pretreatment GH and IGF-I levels. It had an accuracy of 86.3%, positive predictive value of 83.3% and negative predictive value of 87.5%. CONCLUSION: We developed a ML-based prediction model with high accuracy that has the potential to improve medical management of acromegaly, optimize biochemical control, decrease long-term morbidities and mortality, and reduce health services costs.

Lipid profile and response to statin therapy in patients with hypopituitarism.

OBJECTIVE: Dyslipidemia is prevalent among patients with hypopituitarism, especially in those with growth hormone (GH) deficiency. This study aimed to evaluate the response to statin therapy among adult patients with dyslipidemia and hypopituitarism. METHODS: A total of 113 patients with hypopituitarism following up at a neuroendocrinology unit were evaluated for serum lipid levels. Dyslipidemia was diagnosed in 72 (63.7%) of these patients. A control group included 57 patients with dyslipidemia and normal pituitary function. The distribution of gender, age, weight, and dyslipidemia type was well balanced across both groups, and all participants were treated with simvastatin at doses adjusted to obtain normal lipid levels. RESULTS: Patients with hypopituitarism and dyslipidemia presented deficiency of TSH (69%), gonadotropins (69%), ACTH (64%), and GH (55%) and had a similar number of deficient pituitary axes compared with patients with hypopituitarism but without dyslipidemia. All patients with dyslipidemia (with and without hypopituitarism) had lipid levels well controlled with doses of simvastatin ranging from 20-40 mg/day. The mean daily dose of simvastatin was not significantly different between patients with and without hypopituitarism (26.7 versus 23.5 mg, p = 0.10). Similarly, no significant variation in simvastatin dose was observed between patients with different causes of hypopituitarism, presence or absence of GH deficiency, number of deficient pituitary axes, prior pituitary radiation therapy or not, and presence or absence of obesity. CONCLUSION: Patients with GH deficiency without GH replacement showed good response to simvastatin at a mean dose equivalent to that used in individuals with dyslipidemia and normal pituitary function.

Lipid profile and response to statin therapy in patients with hypopituitarism

ABSTRACT Objective: Dyslipidemia is prevalent among patients with hypopituitarism, especially in those with growth hormone (GH) deficiency. This study aimed to evaluate the response to statin therapy among adult patients with dyslipidemia and hypopituitarism. Subjects and methods: A total of 113 patients with hypopituitarism following up at a neuroendocrinology unit were evaluated for serum lipid levels. Dyslipidemia was diagnosed in 72 (63.7%) of these patients. A control group included 57 patients with dyslipidemia and normal pituitary function. The distribution of gender, age, weight, and dyslipidemia type was well balanced across both groups, and all participants were treated with simvastatin at doses adjusted to obtain normal lipid levels. Results: Patients with hypopituitarism and dyslipidemia presented deficiency of TSH (69%), gonadotropins (69%), ACTH (64%), and GH (55%) and had a similar number of deficient pituitary axes compared with patients with hypopituitarism but without dyslipidemia. All patients with dyslipidemia (with and without hypopituitarism) had lipid levels well controlled with doses of simvastatin ranging from 20-40 mg/day. The mean daily dose of simvastatin was not significantly different between patients with and without hypopituitarism (26.7 versus 23.5 mg, p = 0.10). Similarly, no significant variation in simvastatin dose was observed between patients with different causes of hypopituitarism, presence or absence of GH deficiency, number of deficient pituitary axes, prior pituitary radiation therapy or not, and presence or absence of obesity. Conclusions: Patients with GH deficiency without GH replacement showed good response to simvastatin at a mean dose equivalent to that used in individuals with dyslipidemia and normal pituitary function.

DNA repair and cell synthesis proteins: immunohistochemical expression and correlation with recurrence-regrowth in meningiomas.

Meningiomas are considered the second most common neoplasm of the central nervous system in adults. Most of them are benign with slow growth, frequent in women and with a high recurrence rate. In tumors, DNA error repair processes lose efficacy, providing mutagenesis and genomic instability. This work evaluated the expression of proteins involved in cell synthesis (cyclin D1) and DNA errors repair (MUTYH, XPF, XPG) in meningiomas, relating them to clinical, tumor and survival variables. The study included 85 patients, with a mean age of 52 ± 13.3 years and most of them women (2:1 ratio). Sixty-seven cases were grade I (79%). Grade II tumors were independent predictors of recurrence-regrowth (HR: 2.8; p = 0.038). The high expression of cyclin D1 was associated with grade II (p = 0.001) and low MUTYH expression with grade I (p = 0.04). Strong expression of XPF and XPG was associated with grade II (p = 0.002; p < 0.001) and with recurrence-regrowth (p = 0.04; p = 0.003). Strong XPF expression was significantly related to large tumors (p = 0.03). An association of cyclin D1, MUTYH and XPF were found. Survival was not associated with the expression of any of the proteins studied. To know the role of DNA repair proteins and cell synthesis is important for understanding the processes of origin and tumor development. Grade II meningiomas and strong expression of XPF and XPG were predictors of recurrence or regrowth and may assist in clinical management, considering the high recurrence of meningiomas and the absence of consensus regarding treatment.

Resolution of headache after reduction of prolactin levels in hyperprolactinemic patients.

METHODS: Prolactin (PRL) secreting adenomas are associated with high incidence of headache. The role of hyperprolactinemia in the headache context is not clear, nor is the effect of its treatment on headache. The present longitudinal study evaluated hyperprolactinemic patients (69), in terms of presence and characteristics of headache before and after hyperprolactinemia treatment. RESULTS: Headache was reported by 45 (65.2%) patients, independent of the etiology of hyperprolactinemia. The migraine phenotype was the most prevalent (66.6%). Medications used in the treatment of headache not changed during the study. The first line of treatment of hyperprolactinemia was dopaminergic agonists. In the last reevaluation, PRL level under treatment was within the reference range in 54.7% of the cases, and it was observed complete or partial resolution of the headache in 75% of the cases. The median PRL at this time in patients with complete headache resolution was 17 ng/mL, in those who reported partial recovery was 21 ng/mL, and in those in whom the headache did not change was 66 ng/mL, with a significant difference between the group with complete headache resolution vs. the group with unchanged headache (p=0.022). In the cases with complete headache resolution, the median fall on PRL levels was 89% and in those cases with partial headache resolution 86%, both significantly different (p<0.001) from the fall in the cases with an unchanged headache. CONCLUSION: Data allow us to conclude that, in this series, in the majority of cases the reduction in the level of PRL was followe3d by cessation or relief of the pain.

Resolution of headache after reduction of prolactin levels in hyperprolactinemic patients / Resolução de cefaleia após redução dos níveis de prolactina em pacientes com hiperprolactinemia

Abstract Prolactin (PRL) secreting adenomas are associated with high incidence of headache. The role of hyperprolactinemia in the headache context is not clear, nor is the effect of its treatment on headache. Methods: The present longitudinal study evaluated hyperprolactinemic patients (69), in terms of presence and characteristics of headache before and after hyperprolactinemia treatment. Results: Headache was reported by 45 (65.2%) patients, independent of the etiology of hyperprolactinemia. The migraine phenotype was the most prevalent (66.6%). Medications used in the treatment of headache not changed during the study. The first line of treatment of hyperprolactinemia was dopaminergic agonists. In the last reevaluation, PRL level under treatment was within the reference range in 54.7% of the cases, and it was observed complete or partial resolution of the headache in 75% of the cases. The median PRL at this time in patients with complete headache resolution was 17 ng/mL, in those who reported partial recovery was 21 ng/mL, and in those in whom the headache did not change was 66 ng/mL, with a significant difference between the group with complete headache resolution vs. the group with unchanged headache (p=0.022). In the cases with complete headache resolution, the median fall on PRL levels was 89% and in those cases with partial headache resolution 86%, both significantly different (p<0.001) from the fall in the cases with an unchanged headache. Conclusion: Data allow us to conclude that, in this series, in the majority of cases the reduction in the level of PRL was followe3d by cessation or relief of the pain.

Resumo Os adenomas secretores de prolactina (PRL) estão associados à alta incidência de cefaleia. O papel da hiperprolactinemia no contexto da dor de cabeça não está claro, nem o efeito da redução dos níveis da PRL na cefaleia. Métodos: O presente estudo longitudinal avaliou pacientes hiperprolactinêmicos (69), quanto à presença e às características da cefaleia antes e após o tratamento da hiperprolactinemia. Resultados: Cefaleia foi relatada por 45 (65,2%) pacientes, independente da etiologia da hiperprolactinemia. O fenótipo de enxaqueca foi mais prevalente (66,6%). Os medicamentos usados ​​no tratamento da cefaleia não foram alterados durante o estudo. A primeira linha de tratamento da hiperprolactinemia foram os agonistas dopaminérgicos. Na última reavaliação, o nível de PRL sob tratamento estava dentro da faixa de referência em 54,7% dos casos, observando-se resolução completa ou parcial da cefaleia em 75% dos casos. A mediana de PRL neste momento em pacientes com resolução completa da cefaleia foi de 17 ng/mL, nos que relataram recuperação parcial foi de 21 ng/mL, e naqueles em que a cefaleia não se alterou foi de 66 ng/mL, com uma diferença significativa entre o grupo com resolução completa da cefaleia versus o grupo com cefaleia inalterada (p=0,022). Nos casos com resolução completa da cefaleia, a queda mediana nos níveis de PRL foi de 89% e nos casos com resolução parcial de cefaleia de 86%, ambos significativamente diferentes (p<0,001) da queda nos casos com cefaleia inalterada. Conclusão: Os dados permitem concluir que, nesta série, na maioria dos casos, a redução do nível de PRL foi seguida pela cessação ou alívio da dor.

Health-related Quality of Life in Acromegaly Patients: Results from Generic and Disease-specific Questionnaires.

INTRODUCTION: Acromegaly is associated with high morbidity, but still controversial impact on the overall quality of life (QoL). MATERIAL AND METHODS: We evaluated QoL using a generic (SF-36) and a disease-specific questionnaire (AcroQoL) in an acromegalic cohort. RESULTS: Sixty-nine patients answered the questionnaires and had their records reviewed. In the SF-36 questionnaire, except for the Social Aspects domain, all others revealed a reduction in scores from 9.7 to 38.9%, when compared to the non-acromegalics. The cure was positively correlated with mental health (P = 0.023) and drug control was correlated with mental health (P = 0.023) and functional capacity (P = 0.013). In the AcroQoL questionnaire, the mean scores ranged from 54.7% to 72.8%. The use of antidepressants correlated with lower scores on the total AcroQoL (P = 0.039) and physical complaints (P = 0.003). The growth hormone value at diagnosis showed an inverse correlation with the total AcroQoL score (P = 0.014), Appearance Issues subscale (P = 0.081), and Personal Relations (P = 0.002). IGF-1 values at diagnosis and at the last visit showed no statistical correlation with any of the questionnaires. CONCLUSION: The finding of a reduction in QoL scores with both SF-36 and AcroQoL allows us to suggest this evaluation as part of the initial assessment and follow-up in acromegaly, to act globally on the individual's health condition.

Risk factors related to seropositivity for Leptospira spp. in horses in the Serra Catarinense region / Fatores de risco relacionados a soropositividade para Leptospira spp. em equinos na região da Serra Catarinense

ABSTRACT: Leptospirosis is a zoonotic infectious disease caused by the bacterium Leptospira spp. The consequences of infection in horses are unclear, and the serogroups involved vary depending on the region. This study aimed to evaluate the seropositivity of unvaccinated horses in the Serra Catarinense region and the possible risk factors associated with the infection. We used 207 horses from 26 properties, with no clinical history of infection and unvaccinated for leptospirosis. We submitted serum samples to the microscopic agglutination serum (SAM) to obtain the main reference serogroups. We considered animals with titre ≥100 as infected. The results of the serology revealed seropositivity in 45.4% (94/207) of the animals studied. The most frequent antibodies reportedwere those against the serogroups Australis 16.9% (35/207), Ichterhaemorrhagiae 14.4% (30/207), and Grippotyphosa 5.31% (11/207). Among the primary risk factors associated with the infection we reported extensive rearing system (OR = 1.27; P<0.05) and the presence of other animal species such as cattle (OR = 3.85; P<0.01) and capybaras (OR = 2.07; P=0.06). The findings presented in this study showed that leptospirosis is endemic in horses in the Serra Catarinense region, and revealed the need for emergency surveillance and control measures specific to this important zoonosis.

RESUMO: A leptospirose é uma doença infecciosa zoonótica, causada pela bactéria Leptospira spp. Em equinos, as consequências da infecção não são claras e os sorogrupos envolvidos variam dependendo da região. Sendo assim, este trabalho objetivou avaliar a soropositividade de Leptospira spp. em equinos não vacinados na região serrana Catarinense e estimar os possíveis fatores de risco associados à infecção. Para tal, foram estudados 207 equinos, de 26 propriedades, sem histórico clínico da infecção e não vacinados para leptospirose. As amostras de soro foram submetidas ao ensaio de soro aglutinação microscópica (SAM) para os principais sorogrupos de referência. Animais com título ≥100 foram considerados reagentes. Os resultados da sorologia revelaram uma soropositividade de 45,4% (94/207) para os animais estudados. Com maior frequência foram observados anticorpos contra os sorogrupos Australis 16,9% (35/207), Icterohaemorrhagiae 14,4% (30/207), e Grippotyphosa 5,31% (11/207). Dentre os principais fatores de risco associados à infecção observados, foram o sistema de criação extensivo (OR=1,27; P<0,05) e a presença de outras espécies animais como bovinos (OR=3,85; P<0,01) e capivaras (OR=2,07; P=0,06). Os achados apresentados neste estudo mostraram que a leptospirose em equinos é endêmica na região da serra Catarinense, e revelam a necessidade de medidas emergenciais de vigilância e controle específicas para esta importante zoonose.

Assessment of Anthropometric and Physical Health Indicators before and after Pituitary Surgery in Patients with Nonfunctioning Pituitary Adenomas, Acromegaly, and Cushing Disease.

INTRODUCTION: Individuals with pituitary adenomas may have organic consequences of their disease or therapy, and psychological changes can compromise their quality of life (QoL). This study aimed to determine the anthropometric profile and health indicators of patients with pituitary adenoma before and after pituitary surgery. METHODS: Forty-four patients were included in this study. Out of these, 22 patients had nonfunctioning adenomas (50%), 17 acromegaly (38.6%), and 5 patients with Cushing's disease (11.4%). Anthropometric measurements included body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR). Health indicators included body fat percentage (BF%), basal metabolic rate (BMR), maximal oxygen uptake (VO2 max), and hand grip strength. Physical activity level (the International Physical Activity Questionnaire [IPAQ]), subjective perception of health, body image (Body Shape Questionnaire), body satisfaction (Stunkard Figure Rating Scale) were used. RESULTS: The mean patient age was 47.2 ± 14.6 years; of which 25 were women (56.8%). Before surgery, 75.0% were overweight or obese, 84.1% had WC with risk of metabolic complications, and 90.0% had WHR with cardiovascular risk. There was a high BF% in 56.4% of cases, low BMR in 65.1%, lower VO2 max in 16.2%, and below-average grip strength in 88.6%. Hypopituitary patients had poorer cardiorespiratory fitness. The IPAQ showed reduction in physical activity, and 79.5% of patients were dissatisfied with their body image. Patients with nonfunctioning adenomas had better perception of their health while those with Cushing's disease had more distorted body image. Postoperatively, patients with acromegaly showed improvement in WHR and physical activity level, and patients with Cushing's disease showed improvement in anthropometric variables. CONCLUSIONS: These findings emphasize the need for continuous monitoring of this population for anthropometric indicators associated with metabolic and cardiovascular comorbidities as well as body satisfaction.

The acromegalic spine: fractures, deformities and spinopelvic balance.

INTRODUCTION: Axial skeleton arthropathy and osteoporotic vertebral fractures are common findings in acromegalic patients and can result in severe spinal deformity. OBJECTIVE: To investigate the presence of spinal fractures and deformities, sagittal imbalances, and spinopelvic compensatory mechanisms in acromegalics. PATIENTS AND METHODS: 58 patients with acromegaly from a referral neuroendocrinology center were prospectively evaluated by panoramic spine radiographs to detect the presence of fractures and scoliosis, to measure thoracic kyphosis, lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT) and sagittal vertical axis (SVA). Sagittal imbalance criteria were considered: thoracic kyphosis > 50°, PI-LL > 10°, PT > 20° and SVA > 5 cm. Their medical records were analyzed for clinical and laboratorial data. RESULTS: The prevalence of fractures was 13.8%, predominantly in the thoracic spine, with mild and anterior wedge compressions. Scoliosis was present in 34.5% of the cases, all with degenerative lumbar curve apex. Thoracic kyphosis > 50º occurred in 36.8% of patients, PI-LL > 10° in 48.3%, PT > 20° in 41.4% and SVA > 5 cm in 12.1%. CONCLUSION: Increased number of vertebral fractures and high prevalence of spinal deformities related to sagittal imbalance were detected, indicating the importance of monitoring bone comorbidities in acromegaly, with radiological evaluation of the spine as part of the follow up.

PTTG overexpression in non-functioning pituitary adenomas: Correlation with invasiveness, female gender and younger age.

BACKGROUND: Non-functioning pituitary adenomas (NFPA) are prevalent pituitary neoplasms. Because they do not present with hormonal hypersecretion, there is no marker that indicates regrowth or recurrence, as in other adenomas. OBJECTIVES: Evaluate the immunohistochemical expression of PTTG, CD105 and Ki-67 and their relationships with age, gender, invasiveness, hormonal expression and regrowth or recurrence in the follow-up of NFPA operated and not submitted to radiotherapy. METHODS: Included 56 patients submitted to transsphenoidal surgery. Clinical data were obtained from medical records. The invasion degree was obtained by Hardy's classification. RESULTS: Mean age 55 ±â€¯13.6 years, 62.5% men and 68% invasive. Lesion persistence was present in 62.2% and regrowth in 35.7%. The recurrence-free survival rate was 94.5%, 75.4% and 69.1% (1, 2 and 3 years). No patient presented recurrence. The PTTG was positive in 55.3%, with statistically significant relationship with invasiveness, age and female gender, without relation to regrowth. The microvascular density showed statistically significant relationship with male gender, negative correlation with PTTG (r = -0.434, p = 0.001), and no relation with invasiveness and regrowth. The Ki-67 showed statistically significant relationship with age, tendency towards regrowth (p = 0.054) and, with no relation to invasiveness. CONCLUSIONS: It is suggested that PTTG can be used as a prognostic marker in NFPA.

EVALUATION OF TREATMENT OF CENTRAL HYPOTHYROIDISM VERSUS PRIMARY HYPOTHYROIDISM IN RELATION TO LEVOTHYROXINE REPLACEMENT DOSE.

Objective: The aim of this study was to evaluate levothyroxine (LT4) replacement daily doses in patients with central hypothyroidism (CeH) and compare them with those adequate for patients with primary hypothyroidism (P-HYPO). Methods: We included 53 patients with CeH and 57 with P-HYPO, matched by sex, age, weight, and body mass index, in the period of 1 year. At the time of inclusion, all presented a stable and adequate dose of LT4 for at least 3 months, considering as adequate the dose associated with normal thyroid-stimulating hormone (TSH) levels and free thyroxine (T4) in P-HYPO patients, and free T4 levels in CeH patients. Results: The absolute daily dose of LT4 differed significantly between the two groups, 103.0 ± 27.1 µg (CeH) and 89.3 ± 32.0 µg (P-HYPO) (P = .017), even after adjustment for age, gender, and free T4 (P = .04). The LT4 dose adjusted to weight was also higher after adjustment for age, gender and free T4 (P = .04), with an average of 1.3 ± 0.4 µg/kg (CeH) and 1.2 ± 0.4 µg/kg (P-HYPO). Sheehan syndrome patients had a lower absolute daily dose of LT4 (P = .001), and patients who underwent pituitary radiotherapy required higher doses (P = .008). There was no difference in the daily dose of LT4 according to other pituitary hormone deficiencies. Conclusion: The results reinforce the relevance of a careful individualization of LT4 replacement in CeH management and the need for new markers for proper LT4 replacement therapy in such cases. Abbreviations: BMI = body mass index; CeH = central hypothyroidism; GH = growth hormone; LT4 = levothyroxine; P-HYPO = primary hypothyroidism; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone.

Evaluation of the potential of the Ki67 index to predict tumor evolution in patients with pituitary adenoma.

The aggressive course of a number of pituitary adenomas requires the investigation of potential predictors. This study aimed to investigate the proliferation marker Ki67 as a predictor of postoperative outcome in patients with pituitary adenoma regarding recurrence and regrowth of the tumor, using a Ki67 cut-off value of 3%. This retrospective study included 52 patients with pituitary adenoma who had undergone adenomectomy and had a pituitary image taken at least 1 year after surgery. Patients were divided according to Ki67 expression into high (≥3%) vs. low (<3%) levels of Ki67. The two groups were similar regarding the preoperative tumor invasion grade. The Ki67 index ranged from 0 to 30%; in 23 cases, Ki67 was ≥3%. The two groups were similar regarding tumor recurrence and regrowth: 4 cases (28%) of recurrence in the Ki67<3% group vs. none in the Ki67≥3% group (P=0.26); and 2 cases (13%) of regrowth in the Ki67<3% group vs. 7 cases (43%) in the Ki67≥3% group (P=0.11). A subgroup analysis was performed for nonfunctioning adenomas. Recurrence rates remained similar between groups (Ki67<3% group: 1 case [20%]; Ki67≥3% group: none; P>0.99), whereas regrowth rates were higher in the Ki67≥3% group (6 cases [67%] vs. 2 cases [17%] in the Ki67<3% group; P=0.03). The patient with the highest Ki67 index (30%) developed pituitary carcinoma. The results allow us to suggest the adoption of a stricter control of image monitoring in nonfunctioning adenomas with incomplete resection associated with a Ki67 index ≥3%.

Gene and protein expression of E-cadherin and NCAM markers in non-functioning pituitary adenomas.

Non-functioning pituitary adenomas (NFPA) are classified as benign tumors of slow growth, but 40% of them present local invasion, a characteristic of behavior still unpredictable with the use of current tumor markers. This work aims to evaluate the tissue markers E-cadherin and NCAM, which act on cell adhesion, in tumor tissue samples of NFPA and its relationship with the degree of local invasiveness. Gene expression of E-cadherin (CDH1) and NCAM (NCAM1) was assessed by real-time PCR and tissue expression by immunohistochemistry. Fifty-three patients with macroadenomas were submitted to transsphenoidal surgery, presented grade II invasive adenomas in 16 cases (30.2%), grade III in 7 (13.2%) and grade IV in 30 (56.6%). In the immunohistochemistry, one case was negative for E-cadherin, 7 showed weak immunostaining, 17 moderate and 28 strong, whereas for NCAM, 5 showed negative, 28 weakly, 14 moderate and 6 strong. Regarding gene expression, 43.3% showed expression for CDH1 (mean of 2.12) and 50% for NCAM1 (mean of 1.86). There was no significant correlation between the immunohistochemical expression of the markers, as well as the gene expression, the degree of invasiveness and clinical data. The results suggest that E-cadherin and NCAM markers are not directly related to the invasiveness in NFPA.

Clinical and pathological correlations of C4d immunostaining and its influence on the outcome of kidney transplant recipients.

INTRODUCTION: C4d is a marker of antibody-mediated rejection (ABMR) in kidney allografts, although cellular rejection also have C4d deposits. OBJECTIVE: To correlate C4d expression with clinico-pathological parameters and graft outcomes at three years. METHODS: One hundred forty six renal transplantation recipients with graft biopsies by indication were included. C4d staining was performed by paraffin-immunohistochemistry. Graft function and survival were measured, and predictive variables of the outcome were determined by multivariate Cox regression. RESULTS: C4d staining was detected in 48 (31%) biopsies, of which 23 (14.7%) had diffuse and 25 (16%) focal distribution. Pre-transplantation panel reactive antibodies (%PRA) class I and II were significantly higher in C4d positive patients as compared to those C4d negative. Both glomerulitis and pericapillaritis were associated to C4d (p = 0.002 and p < 0.001, respectively). The presence of C4d in biopsies diagnosed as no rejection (NR), acute cellular rejection (ACR) or interstitial fibrosis/ tubular atrophy (IF/TA) did not impact graft function or survival. Compared to NR, ACR and IF/TA C4d⁻, patients with ABMR C4d⁺ had the worst graft survival over 3 years (p = 0.034), but there was no difference between ABMR versus NR, ACR and IF/TA that were C4d positive (p = 0.10). In Cox regression, graft function at biopsy and high %PRA levels were predictors of graft loss. CONCLUSIONS: This study confirmed that C4d staining in kidney graft biopsies is a clinically useful marker of ABMR, with well defined clinical and pathological correlations. The impact of C4d deposition in other histologic diagnoses deserves further investigation.

Clinical and pathological correlations of C4d immunostaining and its infl uence on the outcome of kidney transplant recipients / Correlações clinico-patológicas da marcação de C4d e sua influência na evolução de receptores de transplante renal

INTRODUCTION: C4d is a marker of antibody-mediated rejection (ABMR) in kidney allografts, although cellular rejection also have C4d deposits. OBJECTIVE: To correlate C4d expression with clinico-pathological parameters and graft outcomes at three years. METHODS: One hundred forty six renal transplantation recipients with graft biopsies by indication were included. C4d staining was performed by paraffin-immunohistochemistry. Graft function and survival were measured, and predictive variables of the outcome were determined by multivariate Cox regression. RESULTS: C4d staining was detected in 48 (31 percent) biopsies, of which 23 (14.7 percent) had diffuse and 25 (16 percent) focal distribution. Pre-transplantation panel reactive antibodies ( percentPRA) class I and II were significantly higher in C4d positive patients as compared to those C4d negative. Both glomerulitis and pericapillaritis were associated to C4d (p = 0.002 and p < 0.001, respectively). The presence of C4d in biopsies diagnosed as no rejection (NR), acute cellular rejection (ACR) or interstitial fibrosis/ tubular atrophy (IF/TA) did not impact graft function or survival. Compared to NR, ACR and IF/TA C4d-, patients with ABMR C4d+ had the worst graft survival over 3 years (p = 0.034), but there was no difference between ABMR versus NR, ACR and IF/TA that were C4d positive (p = 0.10). In Cox regression, graft function at biopsy and high percentPRA levels were predictors of graft loss. CONCLUSIONS: This study confirmed that C4d staining in kidney graft biopsies is a clinically useful marker of ABMR, with well defined clinical and pathological correlations. The impact of C4d deposition in other histologic diagnoses deserves further investigation.

INTRODUÇÃO: A fração do complemento C4d é um marcador de rejeição mediada por anticorpos (RMA) em aloenxertos renais, embora na rejeição celular também se observem depósitos de C4d. OBJETIVOS: Correlacionar a expressão de C4d com parâmetros clínicopatológicos e a evolução do enxerto renal em três anos. MÉTODOS: Foram incluídos 146 receptores de transplante renal com biópsias por indicação. A marcação de C4d foi feita por imuno-histoquímica em parafina. Foram medidas a função e a sobrevida do enxerto e determinadas as variáveis preditivas de sua evolução por meio de modelo de regressão de Cox. RESULTADOS: A marcação positiva para C4d foi detectada em 48 (31 por cento) biópsias, das quais 23 (14,7 por cento) tinham marcação difusa e 25 (16 por cento), focal. A reatividade contra painel ( por centoPRA) de classe I e II pré-transplante foi significativamente maior nos pacientes C4d+ quando comparada aos C4d-. Tanto glomerulite quanto pericapilarite foram associadas com C4d (p = 0,002 e p < 0,001, respectivamente). A presença de C4d em biópsias sem rejeição (SR), rejeição celular aguda (RCA) ou fibrose intersticial/atrofia tubular (FI/AT) não teve impacto na função ou na sobrevida do enxerto. Comparados a indivíduos com SR, RCA e FI/AT C4d-, pacientes com RMA C4d+ tiveram pior sobrevida do enxerto em 3 anos (p = 0,034), mas não houve diferença entre RMA versus SR, RCA e FI/AT C4d+ (p = 0,10). Na regressão de Cox, função do enxerto no momento da biópsia e por centoPRA alto foram preditores de perda do enxerto. CONCLUSÕES: A pesquisa de C4d em biópsias do enxerto renal é útil para identificar RMA, com correlações clínicopatológicas bem definidas. O impacto do C4d em outros diagnósticos histológicos necessita de investigação adicional.

Técnica de assinatura digital no câncer de reto / Technique of digital signature in the rectal cancer

A análise das alterações morfométricas e densimétricas nucleares das células neoplásicas malignas tem sido investigada em diferentes tumores. A técnica conhecida como assinatura digital se baseia na obtenção de imagens de núcleos celulares que são computadorizadas e traduzidas graficamente em histogramas representativos do conjunto de características cariométricas e de cromatina da célula investigada. Estudos têm demonstrado o potencial de aplicação da assinatura digital no diagnóstico e definição de prognóstico em diferentes tipos de câncer. Neste artigo, relatamos nossa experiência no emprego da técnica em pacientes com adenocarcinoma primário de reto.