Morning serum cortisol role in the adrenal insufficiency diagnosis with modern cortisol assays.

PURPOSE: To investigate the accuracy of cutoff values of the morning serum cortisol (MSC) using the cortisol stimulus test (CST) insulin tolerance test (ITT) and 250 mcg short Synacthen test (SST) as the reference standard tests, to better define its clinical role as a tool in the diagnostic investigation of adrenal insufficiency (AI) AI. METHODS: An observational study was conducted with a retrospective analysis of MSC in adult patients who had been submitted to a CST to investigate AI between January 2014 and December 2020. The normal cortisol response (NR) to stimulation was defined based on the cortisol assay. RESULTS: 371 patients underwent CST for suspected AI, 121/371 patients (32.6%) were diagnosed with AI. ROC curve analysis showed an area under the curve (AUC) for MSC of 0.75 (95% CI 0.69 - 0.80). The best MSC cutoff values to confirm AI were < 3.65, < 2.35 and < 1.5 mcg/dL with specificity of 98%, 99%, and 100%, respectively. MSC > 12.35, > 14.2 and > 14.5 mcg/dL had sensitivity of 98%, 99%, and 100%, respectively, being the best cutoff values to exclude AI. Almost 25% of patients undergoing CST for possible AI had MSC values between < 3.65 mcg/dL (6.7% of patients) and > 12.35 mcg/dL (17.5% of patients), making the formal CST testing unnecessary if we consider these cutoff values. CONCLUSION: With the most modern cortisol assays, MSC could be used as a diagnostic tool, with high accuracy to confirm or exclude AI, avoiding unnecessary CST; thus, reducing expenses and safety risks during AI investigation.

Adrenal incidentaloma as a novel independent predictive factor for periodontitis.

PURPOSE: There are no data regarding periodontal derangements in patients with adrenal incidentalomas (AI). We assessed the frequency and severity of periodontitis in patients with AI [non-functioning adrenal incidentaloma (NFAI) and possible autonomous cortisol secretion (ACS)] and compared with individuals with normal adrenal. METHODS: A cross-sectional study evaluated thirty-five individuals with AI and 26 controls. NFAI and possible ACS diagnosis was based on the current guidelines: NFAI [cortisol levels after 1 mg dexamethasone suppression test (1 mg-DST) ≤ 1.8 µg/dL (≤ 50 nmol/L)]; possible ACS [cortisol levels after 1 mg-DST 1.9-5.0 µg/dL (51-138 nmol/L)]. Sociodemographic data were collected, and a full-mouth periodontal evaluation was performed. RESULTS: There was no significant difference between groups regarding age, sex, income, ethnicity, education level, smoking, body mass index, dysglycemia, and arterial hypertension. Patients with AI exhibited worse periodontal conditions than controls for the following periodontal clinical parameters: mean percentage of probing pocket depth (PPD) and clinical attachment level (CAL) ≥ 5 mm (p < 0.001 and p = 0.006, respectively). Patients with NFAI and possible ACS showed higher gingival bleeding index (p = 0.014), bleeding on probing (p < 0.001), and CAL (p < 0.001) means compared to controls. The frequencies of periodontitis were 72.7% in patients with NFAI, 84.6% in possible ACS, and 30.8% in controls (p = 0.001). Periodontitis was more severe in patients with possible ACS than NFAI and controls. Patients with NFAI and possible ACS exhibited odds ratio for periodontitis of 4.9 (p = 0.016) and 8.6 (p = 0.02), respectively. CONCLUSION: Patients with AI have higher frequency and severity of periodontitis than controls. The presence of AI was an independent predictive factor for periodontitis.

Cortisol level after dexamethasone suppression test in patients with non-functioning adrenal incidentaloma is positively associated with the duration of reactive hyperemia response on microvascular bed.

PURPOSE: Data on endothelial derangements in patients with non-functioning adrenal incidentaloma (NFAI) are scarce. METHODS: We investigated if NFAI patients present clinical, biochemical and endothelial alterations compared to individuals without an adrenal lesion and also the associations among these variables. Forty-two NFAI and 40 controls were evaluated. NFAI diagnosis and controls were defined according to the current guidelines and based on a normal adrenal imaging exam, respectively. Body composition was evaluated by dual emission X-ray absorptiometry. Endothelial reactivity was assessed by two methods: tonometry (Endo-PAT®) and laser speckle contrast imaging (LSCI). RESULTS: There were no differences between groups regarding age, gender, ethnicity, smoking status, and statin use. The frequency of metabolic syndrome according to the International Diabetes Federation criteria was 69% and 57.9%, respectively in NFAI and controls (p = 0.36), whereas the atherosclerotic cardiovascular disease (ASCVD) risk was 63.4% and 66.7% (p = 0.81). The clinical, laboratory, and anthropometric characteristics, as well as body composition, were similar between the groups. Additionally, any differences between groups were observed on endothelial reactivity tests. Nevertheless, we noted an association between cortisol levels after 1 mg-dexamethosone suppression test (1 mg-DST) and the duration of post-occlusive reactive hyperemia tested on microcirculation (r = 0.30; p = 0.03). NFAI patients require more antihypertensive drugs to achieve blood pressure control (p = 0.04). The number of antihypertensive drugs used to control blood pressure correlated with cortisol levels after 1 mg-DST (r = 0.29; p = 0.03). CONCLUSIONS: Since both groups herein investigated had a high frequency of metabolic syndrome and ASCVD risk, it might explain similarities observed on endothelial reactivity. Nevertheless, prolonged reactive hyperemia response on microcirculation was correlated with cortisol levels under suppression.

The role of immune checkpoint inhibitor therapy in advanced adrenocortical carcinoma revisited: review of literature.

PURPOSE: Adrenocortical carcinoma (ACC) is a rare disease with few therapeutic options. There is an urgency of new effective therapeutic options for these patients. The role of immune checkpoint inhibitors (ICI) in advanced ACC patients is still unclear. METHODS: We conducted a MEDLINE search using the following string: adrenocortical carcinoma and immunotherapy or checkpoint inhibitors. RESULTS: We found four case series comprising 10 patients, and four prospective studies totaling 115 patients. The response rate (RR) in the group of 10 patients was 1 complete response, 3 partial response (PR), 4 stable disease (SD), and 2 progressive disease (PD). The median progression-free survival (mPFS) ranged from 2 to 31 months and the median overall survival (mOS) ranged from 4.3 to 31 months. The results in the 115 patients from prospective trials was variable, the PR ranged from 6 to 23%, the SD ranged from 18 to 50% and overall disease control rate ranged from 30 to 64%. The mPFS reported varied from 1.8 to 2.6 months while the mOS varied from 10.6 to 24.9 months. There were five patients with sustained response for more than 24 months. The most common treatment-related adverse event (TRAE) was the increase in liver enzymes. No treatment-related deaths were reported. Better results in terms of RR and survival were observed in studies that used pembrolizumab. No predictive biomarker of response was found up to now. CONCLUSION: ICI, mainly pembrolizumab, is a potential therapeutic option, which is safe and associated with prolonged OS benefit, in selected patients with advanced ACC.

Vitamin D deficiency is associated with cortical bone loss and fractures in the elderly.

INTRODUCTION: The role of vitamin D on bone microarchitecture and fragility is not clear. OBJECTIVE: To investigate whether vitamin D deficiency (25(OH)D <20 ng/mL) increases cortical bone loss and the severity of fractures. DESIGN: Cross-sectional study of 287 elderly women with at least one prevalent low-impact fracture. METHODS: Biochemistry, X-rays to identify vertebral fractures (VFs) and to confirm non-vertebral fractures (NonVFs), and high-resolution peripheral quantitative computed tomography (HR-pQCT) to evaluate bone microstructure. RESULTS: Serum 25(OH)D levels were associated with body mass index (BMI: r = -0.161, P = 0.006), PTH (r = -0.165; P = 0.005), CTX (r = -0.119; P = 0.043) and vBMD at cortical bone (Dcomp: r = 0.132; P = 0.033) and entire bone (D100: r = 0.162 P = 0.009) at the distal radius, but not at the tibia. Age and PTH levels were potential confounding variables, but in the multiple linear regressions only BMI (95% CI: 0.11-4.16; P < 0.01), 25(OH)D (95% CI: -0.007 to 1.70; P = 0.05) and CTX (95% CI: -149.04 to 21.80; P < 0.01) predicted Dcomp, while BMI (95% CI: 1.13-4.18; P < 0.01) and 25(OH)D (95% CI: 0.24-1.52; P < 0.01) predicted D100. NonVFs predominated in patients with 25(OH)D <20 ng/mL (P = 0.013). Logistic regression analysis showed a decrease in the likelihood of presenting grade 2-3 VFs/NonVFs for every increase in 25(OH)D (OR = 0.962, 95% CI: 0.940-0.984; P = 0.001), BMI (OR = 0.932, 95% CI: 0.885-0.981; P = 0.007) and D100 at radius (OR = 0.994, 95% CI: 0.990-0.998; P = 0.005). CONCLUSION: In elderly patients with prevalent fractures, vitamin D deficiency was associated with cortical bone loss and severity of fractures.

Evaluation of body composition using dual-energy X-ray absorptiometry in patients with non-functioning adrenal incidentalomas and an intermediate phenotype: Is there an association with metabolic syndrome?

PURPOSE: Metabolic syndrome (MS) and sarcopenia are associated with increased cardiovascular risk. No studies using dual-energy x-ray absorptiometry (DXA) have evaluated association between body composition (BC) changes and MS in adrenal incidentaloma (AI). Our aim was to analyse BC in non-functioning AI (NFAI) and intermediate phenotype (IP) relative to controls and to correlate with cortisol levels. METHODS: Cross-sectional study with 44 NFAI (serum cortisol ≤ 50 nmol/L after the overnight 1 mg dexamethasone suppression test), 27 IP (cortisol 51-138 nmol/L), and 41 controls (normal adrenal on imaging examination) using DXA. Autonomic cortisol secretion (cortisol > 138 nmol/L) was excluded from the study. BC data were compared using criteria for MS (World Health Organization, National Cholesterol Education Program-Adult Treatment Panel-III, American Association of Clinical Endocrinologists (AACE), and International Diabetes Federation). RESULTS: There was no significant difference in clinical data and body mass index (BMI) among the three groups. Waist circumference (WC) was larger in AI vs. controls (p < 0.01). Waist-to-hip ratio was higher in NFAI vs. controls and waist-to-height ratio was higher in IP vs. controls (p = 0.03 and p = 0.02, respectively). The frequency of MS was higher in AI vs. controls. BC was not different among the groups. Patients with AI there was a significant association of MS with both an increase in total fat and body fat index (all criteria), and a significant difference between MS and smaller BMI-adjusted lean mass (AACE, p = 0.036). No correlation of cortisol after 1 mg dexamethasone test with BC or MS. AI and WC were independently associated with MS. CONCLUSIONS: AI presented high frequency of MS and was independently associated with MS. Possible deleterious effects of cortisol secretion seem to initially affect the muscular system.

Apolipoprotein A-I proteolysis in aortic valve stenosis: role of cathepsin S.

Aortic valve stenosis (AVS) is the most common valvular heart disease in the Western world. Therapy based on apolipoprotein A-I (apoA-I), the major protein component of high-density lipoproteins, results in AVS regression in experimental models. Nevertheless, apoA-I degradation by proteases might lead to suboptimal efficacy of such therapy. An activatable probe using a quenched fluorescently labeled full-length apoA-I protein was generated to assess apoA-I-degrading protease activity in plasma derived from 44 men and 20 women with severe AVS (age 65.0 ± 10.4 years) as well as from a rabbit model of AVS. In human and rabbit AVS plasma, apoA-I-degrading protease activity was significantly higher than in controls (humans: 0.038 ± 0.009 vs 0.022 ± 0.005 RFU/s, p < 0.0001; rabbits: 0.033 ± 0.016 vs 0.017 ± 0.005 RFU/s, p = 0.041). Through the use of protease inhibitors, we identified metalloproteinases (MMP) as exerting the most potent proteolytic effect on apoA-I in AVS rabbits (67%, p < 0.05 vs control), while the cysteine protease cathepsin S accounted for 54.2% of apoA-I degradation in human plasma (p < 0.05 vs control) with the maximum effect seen in women (68.8%, p < 0.05 vs men). Accordingly, cathepsin S activity correlated significantly with mean transaortic pressure gradient in women (r = 0.5, p = 0.04) but not in men (r = - 0.09, p = 0.60), and was a significant independent predictor of disease severity in women (standardized beta coefficient 0.832, p < 0.001) when tested in a linear regression analysis. ApoA-I proteolysis is increased in AVS. Targeting circulating cathepsin S may lead to new therapies for human aortic valve disease.

Feelings, perceptions, and expectations of patients during the process of oral cancer diagnosis.

PURPOSE: Communication barriers during the process of cancer diagnosis can adversely affect how patients understand their health, and understanding patient's perceptions and expectations can favor adherence to professional recommendations and their prognosis. This study aimed to describe the sociodemographic characteristics, perceptions, expectations, and psychological symptoms of patients during the process of oral cancer diagnosis. METHODS: Patients were assessed at two time points: pre-biopsy (T0) and post-diagnosis (T1). At T0, 49 patients answered a sociodemographic, perceived social support, lifestyle questionnaire and inventories (anxiety-State-Trait Anxiety Inventory (STAI-S/T), depression-Beck Depression Inventory (BDI), risk drinkers-Alcohol Use Disorders Identification Test (AUDIT)). They also were interviewed concerning their perceptions, feelings, and expectations. At T1, the 29 patients diagnosed with oral cancer were reassessed for anxiety (STAI-E) and depression symptoms. An interview investigated the same aspects at T0. RESULTS: Patient mean age was 59 years old (±13.7) and 73.5 % were men. At T0, depression symptoms were more frequent among cancer patients (83.3 %) than those without the disease (p < 0.05), with a prevalence of 36.7 %. Patients presented anxiety (40.8 %) and alcohol abuse behavior (32.6 %). Associations between characteristics and categories at T0 showed that patients with lower income and living with a partner reported negative feelings (p < 0.05) more frequently, together with negative expectations concerning the diagnosis among older patients (p < 0.05) and those with depressive symptoms (p < 0.05). At T1, negative feelings were more frequently reported among patients with anxiety (p < 0.01) and depression symptoms (p < 0.05). CONCLUSION: Professional support and care regarding the psychological aspects and characteristics of patients is required during the diagnosis process in order to promote patient adhesion and favorable prognosis.

Student self-confidence in coping with uncooperative behaviours in paediatric dentistry.

During paediatric dental treatment, non-collaboration and fearful reactions are frequently observed in the child client. The dentistry student must be prepared to cope with these reactions, particularly considering the importance of the relationship between dentists and patients in the promotion of oral health. The present study aimed to assess undergraduate dentistry students' perceptions of their ability to cope with non-collaboration situations in paediatric dentistry. A Likert-style questionnaire was used to analyse students' self-confidence levels, and proposed solutions to 10 problem situations the students would be likely to encounter were recorded. The questionnaire was administered to two undergraduate dentistry student groups from two different Brazilian Public Faculties, comprising 122 respondents. The self-confidence analysis indicated that it varied according to the extent of the child's reaction and the invasiveness of the procedure. Responses to the open-ended questions were categorised by solution proposed, and the analysis indicated that the most frequent responses were categorised as follows: tranquilising, explanation and restriction. Significant differences were found in tranquilising (with higher values for Faculty 2 than 1, and higher values for female students than male students at Faculty 2) and restriction (with higher values for female students compared with male student at both Faculties). The results and discussion focused on the aspects of training dentistry students' social and behavioural management skills.

Accuracy of telomerase in cervical lesions: a systematic review.

The detection of telomerase activity in cervix may provide information on cervical carcinogenesis and may be a marker to monitor cervical intraepithelial neoplasia transition. A quantitative systematic review was performed to estimate the accuracy of telomerase assay in cervical lesions. Studies that evaluated the telomerase test (telomerase repeated amplification protocol) for the diagnosis of cervix lesions and compared it to paraffin-embedded sections as the diagnostic standard were included. Ten studies were analyzed, which included 1069 women. The diagnostic odds ratio (DOR) for a positive telomerase test for low-grade squamous intraepithelial lesions (Lo-SIL) vs normal or benign lesions was 3.2 (95% CI, 1.9-5.6). The DOR for a positive telomerase test for high-grade squamous intraepithelial lesions (Hi-SIL) vs Lo-SIL, normal or benign lesions was 5.8 (95% CI, 3.1-10). For cervix cancer vs Hi-SIL, the DOR for a positive telomerase test was 8.1 (95% CI, 3.2-20.3) and for cervix cancer vs Lo-SIL, normal or benign lesions, it was 40.9 (95% CI, 18.2-91). Our data support the current hypothesis that telomerase may activate an early event in cervical carcinogenesis that could be associated with the initiation and progression of cervical lesions.

Evaluation of a pregnant guidance program

The aim of the present study was to assess ability of pregnant women (n=82) to acquire guidance on breastfeeding, baby’s sucking habits, and oral hygiene. Subjects were interviewed before and after their enrolment in the pregnancy orientation program at Piracicaba Dental School, University of Campinas (UNICAMP). Results showed that all subjects improved their knowledge on all behavior aspects as well as their ability to follow guidance offered in this study. Information provided during the pre-natal period seems to help reduce incidence of early introduction of foods and weaning. To guarantee the success of programs designed to assist pregnant women, it is wise to use a systematic follow-up to motivate mothers after childbirth to keep up with guidance given in such programs, concerning not only information, but also emotional and instrumental support.

Relation of oral yeast infection in Brazilian infants and use of a pacifier.

The frequency of oral yeast ingestion and its relationship with sucking and feeding habits was described in children from one to 18 months of age. Yeasts were detected in 58.3 percent of children and the most prevalent species were Candida parapsilosis and Candida albicans. The use of a pacifier was positively associated with the frequency of yeast infection and with the levels of these microorganisms in the mouth. No relationship was detected between the prevalence of yeast and breast-feeding or bottle-feeding habits. The results suggest that use of a pacifier is an important local factor in the colonization and proliferation of yeast in the oral cavity.

Cross validation of a Brazilian version of the Dental Fear Survey.

The Dental Fear Survey (DFS), a paper and pencil instrument for assessing dental fear and avoidance, has been widely used and validated in fear studies in the US. However, before such instruments are used in countries and cultures dissimilar to the one in which it was developed, they should be cross-validated in that culture. The present study is an examination of the DFS response characteristics in a group of 374 Brazilian university students. Factor analysis of the DFS revealed three factors essentially identical to those found among university students in the US and in Singapore, as well as among US adult dental patients. Higher DFS scores were significantly associated longer intervals since last dental visit. These results are taken as evidence that the DFS performs in this Brazilian sample very much as it does in other samples; and is thus, a valid indicator of dental fear at least among Brazilian university students.

Shock intensity and signaled avoidance responding.

Five rats were submitted to a signaled free-operant avoidance contingency. Throughout the experiment, shock intensity was varied from 0.1 to 8.0 mA, with shock duration constant at 200 milleseconds. Results indicate: (a) an all-or-none effect of shock intensity on response and shock rates, on percentage of shocks avoided, and on frequency of occurrence of responding during the preshock stimulus; and (b) no systematic effect of shock intensity on stimulus control, measured either by the percentage of stimulus presentations accompanied by a response or by the percentage of responses that occurred during those preshock stimuli. Such results indicate that for each subject there is a minimum shock intensity necessary to establish and maintain avoidance responding; intensities higher than this minimum value have little or no effect on responding (with an upper limit for those strong intensities with a general disruptive effect on behavior).

A doença de Chagas em motoristas de táxi na cidade de Uberlândia / Chagas' disease in taxi drivers in the city of Uberlandia

A prevalencia de sorologia positiva para a doenca de Chagas foi pesquisada em 152 motoristas de taxi de Uberlandia (MG). Houve 21 individuos (13,8%) com diagnostico sorologico de infeccao pelo Trypanosoma cruzi. Destes, 16 casos foram avaliados clinicamente, pelo eletrocardiograma (ECG) convencional e pelo estudo radiologico do torax. Todos eram assintomaticos 9 tinham arritmias cardiacas "benignas" pelo ECG (2 dos quais, com area cardiaca aumentada), 7 mostraram ECG e radiografias do torax normais. Ressalta-se a alta prevalencia da tripanosomiase na amostra. Discute-se a conduta medico-trabalhista a assumir diante dos casos positivos e a necessidade da inclusao de exames laboratoriais para diagnostico da doenca de Chagas, na rotina para a obtencao de carteira de motorista (pelo menos para profissionais) nas areas endemicas

Signalled free-operant avoidance of shock by pigeons pecking a key.

Two pigeons were trained to peck a key under a free-operant avoidance schedule. Then, changes in key color signalled the beginning (safe period) and the end (warning period) of the response-shock interval, with a response required to change the key color. Finally, a change in key color signalled the warning period and either a response or a shock reinstated the safe stimulus. During signalled avoidance, response rate was higher during the warning stimulus than during the safe stimulus. More responding tended to occur in the warning stimulus when it was terminated by either a response or a shock than by only a response. In either procedure, response latency during the warning stimulus was a function of the duration of the warning stimulus. In general, response and shock rate were higher during unsignalled than during signalled avoidance. When the warning stimulus was brief, the results were similar to those of unsignalled avoidance. These results confirm previous findings with pigeons, are in general agreement with data provided by other species in studies of signalled avoidance, and thereby indicate the transituationality of the key-pecking operant.