Arginine or Hypertonic Saline-Stimulated Copeptin to Diagnose AVP Deficiency.

BACKGROUND: Distinguishing between arginine vasopressin (AVP) deficiency and primary polydipsia is challenging. Hypertonic saline-stimulated copeptin has been used to diagnose AVP deficiency with high accuracy but requires close sodium monitoring. Arginine-stimulated copeptin has shown similar diagnostic accuracy but with a simpler test protocol. However, data are lacking from a head-to-head comparison between arginine-stimulated copeptin and hypertonic saline-stimulated copeptin in the diagnosis of AVP deficiency. METHODS: In this international, noninferiority trial, we assigned adult patients with polydipsia and hypotonic polyuria or a known diagnosis of AVP deficiency to undergo diagnostic evaluation with hypertonic-saline stimulation on one day and with arginine stimulation on another day. Two endocrinologists independently made the final diagnosis of AVP deficiency or primary polydipsia with use of clinical information, treatment response, and the hypertonic-saline test results. The primary outcome was the overall diagnostic accuracy according to prespecified copeptin cutoff values of 3.8 pmol per liter after 60 minutes for arginine and 4.9 pmol per liter once the sodium level was more than 149 mmol per liter for hypertonic saline. RESULTS: Of the 158 patients who underwent the two tests, 69 (44%) received the diagnosis of AVP deficiency and 89 (56%) received the diagnosis of primary polydipsia. The diagnostic accuracy was 74.4% (95% confidence interval [CI], 67.0 to 80.6) for arginine-stimulated copeptin and 95.6% (95% CI, 91.1 to 97.8) for hypertonic saline-stimulated copeptin (estimated difference, -21.2 percentage points; 95% CI, -28.7 to -14.3). Adverse events were generally mild with the two tests. A total of 72% of the patients preferred testing with arginine as compared with hypertonic saline. Arginine-stimulated copeptin at a value of 3.0 pmol per liter or less led to a diagnosis of AVP deficiency with a specificity of 90.9% (95% CI, 81.7 to 95.7), whereas levels of more than 5.2 pmol per liter led to a diagnosis of primary polydipsia with a specificity of 91.4% (95% CI, 83.7 to 95.6). CONCLUSIONS: Among adult patients with polyuria polydipsia syndrome, AVP deficiency was more accurately diagnosed with hypertonic saline-stimulated copeptin than with arginine-stimulated copeptin. (Funded by the Swiss National Science Foundation; CARGOx ClinicalTrials.gov number, NCT03572166.).

Remote Emotion Recognition Using Continuous-Wave Bio-Radar System.

The Bio-Radar is herein presented as a non-contact radar system able to capture vital signs remotely without requiring any physical contact with the subject. In this work, the ability to use the proposed system for emotion recognition is verified by comparing its performance on identifying fear, happiness and a neutral condition, with certified measuring equipment. For this purpose, machine learning algorithms were applied to the respiratory and cardiac signals captured simultaneously by the radar and the referenced contact-based system. Following a multiclass identification strategy, one could conclude that both systems present a comparable performance, where the radar might even outperform under specific conditions. Emotion recognition is possible using a radar system, with an accuracy equal to 99.7% and an F1-score of 99.9%. Thus, we demonstrated that it is perfectly possible to use the Bio-Radar system for this purpose, which is able to be operated remotely, avoiding the subject awareness of being monitored and thus providing more authentic reactions.

Evaluation of a new treadmill exercise protocol to unmask type 1 Brugada electrocardiographic pattern: can we improve diagnostic yield?

AIMS: High precordial leads (HPL) on the resting electrocardiogram (ECG) are widely used to improve diagnostic detection of type 1 Brugada ECG pattern (Br1ECGp). A parasympathetic activation marks the initial recovery phase of treadmill stress testing (TET), and this can be useful for detecting the typical ECG pattern. Our study aimed to evaluate the role of a new HPL-treadmill exercise testing (TET) protocol in detecting Br1ECGp fluctuation compared to resting HPL-ECG. METHODS AND RESULTS: 74 out of 163 patients of a Brugada syndrome (BrS) Brazilian cohort (GenBra Registry) underwent exercise testing with HPL-TET protocol. Precordial leads were displayed in strategic positions in the right and left parasternal spaces. The step-by-step analysis included ECG classification (as presence or absence of Br1ECGp) in standard vs. HPL leads placement in the following sequences: resting phase, maximal exercise, and the passive recovery phase (including 'quick lay down'). For heart rate recovery (HRR) measurements and comparisons, a Student's t-test was applied. McNemar tests compared the detection of Br1ECGp. The significance level was defined as P < 0.05. Fifty-seven patients (57/74; 77%) were male, the mean age was 49.0 ± 14, 78.4% had spontaneous BrS, and the mean Shanghai score was 4.5. The HPL-TET protocol increased Br1ECGp detection by 32.4% against resting HPL-ECG (52.7% vs. 20.3%, P = 0.001) alone. CONCLUSION: Stress testing using HPL with the passive recovery phase in the supine position offers an opportunity to unmask the type 1 Br1ECGp, which could increase the diagnostic yield in this population.

Fiber Loop Mirror Based on Optical Fiber Circulator for Sensing Applications.

In this paper, a different Fiber Loop Mirror (FLM) configuration with two circulators is presented. This configuration is demonstrated and characterized for sensing applications. This new design concept was used for strain and torsion discrimination. For strain measurement, the interference fringe displacement has a sensitivity of (0.576 ± 0.009) pm‧µÎµ-1. When the FFT (Fast Fourier Transformer) is calculated and the frequency shift and signal amplitude are monitored, the sensitivities are (-2.1 ± 0.3) × 10-4 nm-1 µÎµ-1 and (4.9 ± 0.3) × 10-7 µÎµ-1, respectively. For the characterization in torsion, an FFT peaks variation of (-2.177 ± 0.002) × 10-12 nm-1/° and an amplitude variation of (1.02 ± 0.06) × 10-3/° are achieved. This configuration allows the use of a wide range of fiber lengths and with different refractive indices for controlling the free spectral range (FSR) and achieving refractive index differences, i.e., birefringence, higher than 10-2, which is essential for the development of high sensitivity physical parameter sensors, such as operating on the Vernier effect. Furthermore, this FLM configuration allows the system to be balanced, which is not possible with traditional FLMs.

Social isolation due to COVID-19: impact on loneliness, sedentary behavior, and falls in older adults.

OBJECTIVES: The World Health Organization has recommended social isolation to prevent the transmission of COVID-19. Thus, feelings of loneliness, sedentary behavior, and predisposition to falls have been reported more often due to the adoption of social isolation, especially for older adults. The objective of this study was to compare older adults' loneliness, sedentary behavior, and occurrence of falls before and during social isolation due to the pandemic as well as to analyze the association of loneliness with sedentary lifestyle and falls in older adults. METHOD: Retrospective analytical study conducted through an online survey with older adults from Brazilian states in social isolation, approved by the Research Ethics Committee (number 32168920.0.0000.0068). RESULTS: There was a significant increase in loneliness and sedentary behavior during social isolation (p-value < 0.05 for both), but no increase was observed for falls (p-value = 0.615). There was no correlation between the outcomes, nor was there a correlation between the outcomes and the number of days in social isolation. CONCLUSION: The results of this research show that adoption of social isolation due to the COVID-19 pandemic brought an increase in sedentary behavior and loneliness for older adults but had no effect on the number of falls.

Functional and joint evaluation in a prospective cohort of patients with severe haemophilia.

INTRODUCTION: Arthropathy is the main morbidity of haemophilia. Periodic joint health assessment enables a better understanding of the limitations of these patients. OBJECTIVE: To evaluate the functional and joint performance in patients with haemophilia at one-year follow-up, as well as its association with prophylactic treatment and attendance at scheduled consultations at a haemophilia treatment centre. METHODS: This prospective cohort study included patients with severe haemophilia aged 7 years or more and treated at Fundação Hemocentro de Brasília, Brazil, from January 2014 to December 2018. The Hemophilia Joint Health Score and Functional Independence Score in Hemophilia were assessed at the first consultation and after a one-year follow-up. RESULTS: The study included 69 patients. The mean age at study recruitment was 22.5 ± 4.5 years, 62.3% of patients aged 18 years or older, and 29 patients were receiving primary prophylaxis (38.0%). There was a positive correlation between HJHS and age and a negative correlation between FISH and age. The worsening HJHS was associated with non-primary prophylaxis and non-attendance at scheduled multidisciplinary consultations. The worsening FISH was associated with non-primary prophylaxis. The correlation between FISH and treatment adherence was significant for the delta. CONCLUSION: The older the patient with haemophilia, the higher the probability of a worsening of the HJHS. In the presence of more arthropathies, the older the patient, the worse the FISH. Patients receiving primary prophylaxis show better results in the HJHS and FISH when compared to patients receiving secondary prophylaxis and/or on-demand treatment.

Effects of oral macimorelin on copeptin and anterior pituitary hormones in healthy volunteers.

PURPOSE: The test with the highest diagnostic accuracy for diabetes insipidus is copeptin measurement after hypertonic saline infusion. However, the procedure is cumbersome and unpleasant due to rapid sodium increase. An oral stimulation test would be highly desirable. Macimorelin, an oral ghrelin agonist, is a newly approved diagnostic test for growth hormone (GH) deficiency, but its effects on copeptin/vasopressin are unknown and the effects on other pituitary hormones only scarcely investigated. METHODS: In this prospective, interventional, proof-of-concept study Copeptin and anterior pituitary hormones were measured in 28 healthy volunteers on two test days at baseline, 30, 45, 60, 90 and 120 min after a single dose of macimorelin (first visit: 0.5 mg/kg, second visit: 0.75 mg/kg). RESULTS: Baseline copeptin levels were 5.26 pmol/L [1.57, 6.81] and did not change after macimorelin intake (0.5 mg/kg: maximal median change 0.40 [- 0.49, 0.65] pmol/L, p = 0.442; 0.75 mg/kg: - 0.13 [- 0.45, 0.17] pmol/L, p = 0.442. Median GH levels increased from 3.67 mU/L with a maximal median change of 94.66 [IQR 56.5; 110.96] mU/L, p < 0.001. No effect was seen on cortisol, ACTH, LH and FSH levels. Prolactin (max. median change 100 [2.5; 146.5] mU/L, p = 0.004) and free thyroxine (fT4) (0.5 [0.2; 0.8] pmol/L, p < 0.001) increased, whereas TSH decreased (- 0.18 [- 0.22, - 0.09] mU/L, p < 0.001). CONCLUSION: We confirm an increase of GH upon macimorelin in healthy volunteers. However, macimorelin did not stimulate copeptin and therefore does not provide an oral test alternative for the diagnosis of diabetes insipidus. Additionally, a stimulatory effect was seen for prolactin and fT4, but not for ACTH and gonadotropic hormones. REGISTRATION: The trial was registered on ClinicalTrials.gov (NCT03844217) on February 18, 2019.

Immersive Virtual Tasks With Motor and Cognitive Components: A Feasibility Study With Young and Older Adults.

OBJECTIVE: To analyze the feasibility, safety, and acceptability of immersive virtual tasks. METHODS: The authors recruited 11 young adults and 10 older adults. The participants performed three virtual reaching tasks while walking on a virtual path. The descriptive analysis and comparison between participants were performed using the Mann-Whitney U test and chi-square test for nonparametric and nominal variables, respectively. The authors also used analysis of variance for a between-groups comparison for normal variables. RESULTS: Twenty percent of older adults and 81.8% of young adults completed all three tasks (chi-square test; p = .005). Both groups reported minor symptoms, with no significant differences. The older adults were more motivated to practice the tasks (Mann-Whitney U test; p = .015) and would be more likely to suggest them to others (chi-square test; p = .034). CONCLUSION: All three tasks were feasible for young adults. All participants, except for one, had cybersickness. The symptoms were mostly mild and subsided once the interaction was complete.

Copeptin response to hypoglycemic stress is linked to prolactin activation in children.

PURPOSE: The physiological role of arginine vasopressin (AVP) in the acute stress response in humans and especially in children is unclear. The aim of this study was to explore the interaction between copeptin, a well-established surrogate marker of AVP release, and anterior pituitary hormone activation in response to acute hypoglycemic stress in children and adolescents. METHODS: We conducted an exploratory single center study involving 77 children and adolescents undergoing insulin-induced hypoglycemia. Blood levels of copeptin, ACTH, cortisol, GH, prolactin, interleukin-6 (IL-6), adrenaline and noradrenaline were determined at baseline and after insulin-induced hypoglycemia. RESULTS: Basal plasma levels of copeptin (median: 5.2 pmol/L) increased significantly after hypoglycemia (median 9.7 pmol/L; P < 0.0001). Subjects with insufficient HPA axis response or severe GH deficiency had lower hypoglycemia-induced copeptin increase (median: 2.3 pmol/L) compared with individuals with intact pituitary response (median: 5.2 pmol/L, P = 0.02). Copeptin increase correlated significantly with the maximal increase of ACTH (rs = 0.30; P = 0.010), cortisol (rs = 0.33; P = 0.003), prolactin (rs = 0.25; P = 0.03), IL-6 (rs = 0.35; P = 0.008) and with BMI-SDS (rs = - 0.28, P = 0.01). In multivariate regression analysis, prolactin increase was the only independent variable associated with copeptin increase (P = 0.0004). CONCLUSION: Our data indicate that: (1) hypoglycemic stress elicits a marked copeptin response in children and adolescents, pointing out its role as an acute stress marker in this population; (2) stress-induced AVP/copeptin release is associated with anterior pituitary activation, mainly a prolactin response.

Pasireotide treatment does not modify hyperglycemic and corticosterone acute restraint stress responses in rats.

Pasireotide is a new-generation somatostatin analog that acts through binding to multiple somatostatin receptor subtypes. Studies have shown that pasireotide induces hyperglycemia, reduces glucocorticoid secretion, alters neurotransmission, and potentially affects stress responses typically manifested as hyperglycemia and increased corticosterone secretion. This study specifically aimed to evaluate whether pasireotide treatment modifies glucose and costicosterone secretion in response to acute restraint stress. Male Holtzman rats of 150-200 g were treated with pasireotide (10 µg/kg/day) twice-daily for two weeks or vehicle for the same period. Blood samples were collected at baseline and after 5, 10, 30, and 60 min of restraint stress. The three experimental groups comprised of vehicle + restraint (VEHR), pasireotide + restraint (PASR), and pasireotide + saline (PASNR). Following pasireotide treatment, no significant differences in baseline glucose and corticosterone levels were observed among the three groups. During restraint, hyperglycemia was observed at 10 min (p < .01 for both comparisons), peaked at 30 min (p < .01 for both comparisons) and showed higher 60 min areas under glucose curves in the VEHR and PASR stressed groups when compared to the non-stressed PASNR group (p < .05 for both comparisons). Restraint also increased corticosterone secretion in the VEHR and PASR stressed groups at 5 min (p < .01 for both comparisons), and peaked at 30 min (p < .01 for both comparisons) with corresponding higher 60 min areas under corticosterone curves when compared to the non-stressed PASNR group (p < .01 for both comparisons). In conclusion, pasireotide treatment does not modify hyperglycemic- and corticosterone-restraint stress responses, thus preserving acute stress regulation.

A COMBINED OUTPATIENT AND INPATIENT OVERNIGHT WATER DEPRIVATION TEST IS EFFECTIVE AND SAFE IN DIAGNOSING PATIENTS WITH POLYURIA-POLYDIPSIA SYNDROME.

OBJECTIVE: The water deprivation test (WDT) is widely used for the differential diagnosis of the polyuria-polydipsia syndrome (PPS). However, it is inconvenient and may not always be precise in differentiating partial forms of diabetes insipidus (DI) from primary polydipsia (PP). The aim of this study was to evaluate the results of a combined outpatient and inpatient overnight WDT protocol that included an overnight unsupervised period concerning its feasibility and safety. METHODS: We performed a retrospective analysis of clinical data and laboratory results of 52 patients with PPS undergoing WDT at a single center. RESULTS: PP was the most frequent diagnosis, followed by complete central DI (cCDI), partial central DI (pCDI), and nephrogenic DI (NDI). Over 90% of the patients showed an expected increase in serum osmolality at the end of the dehydration period. There were no reports of complications during the overnight deprivation period. Post-dehydration urine osmolality and urine-to-serum osmolality ratio significantly differentiated all the groups ( P<.05), except for cCDI and NDI, which could be differentiated by basal and post-dehydration vasopressin (AVP) levels ( P<.05 for both). Although these measurements were useful for differentiating patients according to their allocation groups, results from WDT and direct AVP levels may often require a comprehensive diagnostic approach, particularly in the challenging groups of PP and pCDI. CONCLUSION: A combined outpatient and inpatient overnight WDT protocol is safe and feasible when the test is performed with special care at experienced centers. Newer diagnostic tools are expected to improve the accuracy of PPS diagnosis. ABBREVIATIONS: AQP2 = aquaporin-2; AVP = vasopressin; CDI = central diabetes insipidus; cCDI = complete central diabetes insipidus; DDAVP = desmopressin; DI = diabetes insipidus; IQR = interquartile range; MRI = magnetic resonance imaging; Na+ = sodium; NDI = nephrogenic diabetes insipidus; pCDI = partial central diabetes insipidus; PP = primary polydipsia; PPS = polyuria-polydipsia syndrome; S_osm = serum osmolality; U_osm = urine osmolality; WDT = water deprivation test.

Anesthetic Management of Patients With Morvan Syndrome: A Case Report and Literature Review.

Morvan syndrome is a rare condition distinguished by hyperactivity within the central, autonomic, and peripheral nervous systems. Due to the limited number of cases, this presents clinical challenges stemming from the scarcity of published literature. We present a successful anesthetic approach for a patient diagnosed with Morvan syndrome scheduled for elective major intra-thoracic surgery to remove metastases from a thymoma. The patient had previously undergone thymectomy, with the syndrome being diagnosed only one year after the surgery. Additionally, we conducted a literature review on the anesthetic management of this condition.

Activated AMP-protein kinase (pAMPK) is overexpressed in human somatotroph pituitary adenomas.

INTRODUCTION: AMPK (AMP-activated protein kinase) is an enzyme that acts as a metabolic sensor and regulates multiple pathways via phosphorylating proteins in metabolic and proliferative pathways. The aim of this work was to study the activated cellular AMPK (phosphorylated-AMPK at Thr172, pAMPK) levels in pituitary tumor samples from patients with sporadic and familial acromegaly, as well as in samples from normal human pituitary gland. METHODS: We studied pituitary adenoma tissue from patients with sporadic somatotroph adenomas, familial acromegaly with heterozygote germline variants in the aryl hydrocarbon receptor interacting protein (AIP) gene (p.Q164*, p.R304* and p.F269_H275dup) and autopsy from normal pituitary glands without structural alterations. RESULTS: Cellular levels of pAMPK were significantly higher in patients with sporadic acromegaly compared to normal pituitary glands (p < 0.0001). Tissues samples from patients with germline AIP mutations also showed higher cellular levels of pAMPK compared to normal pituitary glands. We did not observe a significant difference in cellular levels of pAMPK according to the cytokeratin (CAM5.2) pattern (sparsely or densely granulated) for tumor samples of sporadic acromegaly. CONCLUSION: Our data show, for the first time in human cells, an increase of cellular levels of pAMPK in sporadic somatotropinomas, regardless of cytokeratin pattern, as well as in GH-secreting adenomas from patients with germline AIP mutations.

Incomplete recovery of the CD4+/CD8+ ratio is associated with the late introduction of antiretroviral therapy among people living with HIV infection.

Despite being subject to lower AIDS-related mortality rates and having a higher life expectancy, patients with HIV are more prone to develop non-AIDS events. A low CD4+/CD8+ ratio during antiretroviral therapy identifies people with heightened immune senescence and increased risk of mortality. In clinical practice, finding determinants of a low CD4+/CD8+ ratio may be useful for identifying patients who require close monitoring due to an increased risk of comorbidities and death. We performed a prospective study on the evolution of the CD4+/CD8+ ratio in 60 patients infected with HIV (80% males), who were subjected to two different antiretroviral regimens: early and deferred therapy. The initial CD4+/CD8+ ratio was ≤1 for 70% of the patients in both groups. Older age, CD4+ cell count at inclusion, Nadir CD8+T-cell count, and Initial CD4+/CD8+ ratio ≤ 1 were risk factors for lack of ratio recovery. In the multivariate analysis, a CD4+/CD8+ ratio > 1 at the start of the treatment was found to be a determinant factor in maintaining a CD4+/CD8+ ratio > 1. The nadir CD4+T-cell count was lower in the deferred therapy group (p=0.004), and the last CD4+/CD8+ ratio ≤1 was not associated with comorbidities. Ratio recovery was not associated with the duration of HIV infection, time without therapy, or absence of AIDS incidence. A greater improvement was observed in patients treated early (p=0.003). In contrast, the slope of increase was slower in patients who deferred treatment. In conclusion, the increase in the CD4+/CD8+ ratio occurred mostly for patients undergoing early strategy treatment and its extension did not seem to be related to previous HIV-related factors.

Systems bioengineering approaches for developmental toxicology.

Developmental toxicology is the field of study that examines the effects of chemical and physical agents on developing organisms. By using principles of systems biology and bioengineering, a systems bioengineering approach could be applied to study the complex interactions between developing organisms, the environment, and toxic agents. This approach would result in a holistic understanding of the effects of toxic agents on organisms, by considering the interactions between different biological systems and the impacts of toxicants on those interactions. It would be useful in identifying key biological pathways and mechanisms affected by toxic agents, as well as in the development of predictive models to assess potential risks of exposure to toxicants during development. In this review, we discuss the relevance of systems bioengineering to the field of developmental toxicity and provide up-to-date examples that illustrate the use of engineering principles for this application.

Removal of Cr(VI) from water by in natura and magnetic nanomodified hydroponic lettuce roots.

Biosorption is a viable and environmentally friendly process to remove pollutants and species of commercial interest. Biological materials are employed as adsorbents for the retention, removal, or recovery of potentially toxic metals from aqueous matrices. Hexavalent chromium is a potential contaminant commonly used in galvanoplasty and exhibits concerning effects on humans and the environment. The present work used in natura lettuce root (LR) and nanomodified lettuce root (LR-NP) for Cr(VI) adsorption from water medium. The nanomodification was performed by coprecipitation of magnetite nanoparticles on LR. All materials were morphologically and chemically characterized. The conditions used in removing Cr(VI) were determined by evaluating the pH at the point of zero charge (pHPZC = 5.96 and 6.50 for LR and LR-NP, respectively), pH, kinetics, and sorption capacity in batch procedures. The maximum sorption capacity of these materials was reached at pH 1.0 and 30 min of adsorbent-adsorbate contact time. The pseudo-second-order kinetic equation provided the best adjustments with r2 0.9982 and 0.9812 for LR and LR-NP, respectively. Experimental sorption capacity (Qexp) results were 4.51 ± 0.04 mg/g, 2.48 ± 0.57 mg/g, and 3.84 ± 0.08 mg/g for LR, NP, and LR-NP, respectively, at a 10 g/L adsorbent dose. Six isothermal models (Langmuir, Freundlich, Sips, Temkin, DR, and Hill) fit the experimental data to describe the adsorption process. Freundlich best fit the experimental data suggesting physisorption. Despite showing slightly lower Qexp than LR, LR-NP provides a feasible manner to remove the Cr(VI)-containing biosorbent from the medium after sorption given its magnetic characteristic.

Evaluation of Functional and Joint Health and Associated Factors in Adults With Hemophilia From a Developing Country With Government-Backed Efforts to Improve Hemophilia Care.

Introduction Hemophilic arthropathy affects people with hemophilia (PwH) and causes joint dysfunction and disability. Brazil has a unique situation and implemented policies to improve health care for PwH. The aim of this study was to evaluate the Functional Independence Score in Hemophilia (FISH), Hemophilia Joint Health Score (HJHS), and associated factors among adult PwH attending a Hemophilia Comprehensive Care Center in Brazil. Methods A post hoc analysis was conducted, including 31 patients who had submitted to a physical evaluation during a previously published cross-sectional study performed from June 2015 to May 2016 at the Brasília Blood Center Foundation, Brazil. Results The mean age was 30.8±9.4 years, and 80.6% had severe hemophilia. FISH was 27.0±3.8, and HJHS 18.0±10.8. The ankle was the most often affected joint (25/31, 80.6%). There were significant correlations between FISH and HJHS scores and the Hemophilia Quality of Life Questionnaire for Adults. Patients with severe hemophilia (P = 0.029) and PwH aged ≥ 30 years (P = 0.049) had lower FISH scores. Monthly household income > 2 Brazilian minimum wages was independently associated with improved HJHS (P = 0.033). The factors simultaneously associated with better HJHS and FISH were age < 30 years (P = 0.021) and monthly household income < 2 minimum wages (P = 0.013). Conclusion FISH and HJHS showed favorable scores despite being performed in a country with unfavorable socioeconomic conditions. In addition to hemophilia severity and age, monthly household income was independently associated with functional and articular state of PwH. The results highlight the importance of the free provision of coagulation factors in Brazil.

Nephrogenic diabetes insipidus: a comprehensive overview.

Nephrogenic diabetes insipidus (NDI) is characterized by the inability to concentrate urine that results in polyuria and polydipsia, despite having normal or elevated plasma concentrations of arginine vasopressin (AVP). In this study, we review the clinical aspects and diagnosis of NDI, the various etiologies, current treatment options and potential future developments. NDI has different clinical manifestations and approaches according to the etiology. Hereditary forms of NDI are mainly caused by mutations in the genes that encode key proteins in the AVP signaling pathway, while acquired causes are normally associated with specific drug exposure, especially lithium, and hydroelectrolytic disorders. Clinical manifestations of the disease vary according to the degree of dehydration and hyperosmolality, being worse when renal water losses cannot be properly compensated by fluid intake. Regarding the diagnosis of NDI, it is important to consider the symptoms of the patient and the diagnostic tests, including the water deprivation test and the baseline plasma copeptin measurement, a stable surrogate biomarker of AVP release. Without proper treatment, patients may developcomplications leading to high morbidity and mortality, such as severe dehydration and hypernatremia. In that sense, the treatment of NDI consists in decreasing the urine output, while allowing appropriate fluid balance, normonatremia, and ensuring an acceptable quality of life. Therefore, therapeutic options include nonpharmacological interventions, including sufficient water intake and a low-sodium diet, and pharmacological treatment. The main medications used for NDI are thiazide diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs), and amiloride, used isolated or in combination.

"Subclinical atherosclerosis in acromegaly: Possible association with cardiovascular risk factors rather than disease activity".

OBJECTIVE: Cardiovascular (CV) disease is still a major cause of excessive morbidity and mortality in patients with active acromegaly, which may be attributed to a high prevalence of associated pro-atherosclerotic risk factors. However, a direct effect of GH/IGF-1 excess on the vasculature has been previously suggested, warranting further investigation. The present study was designed to investigate whether chronic GH/IGF-1 excess is associated with an increased prevalence of subclinical atherosclerosis in patients with acromegaly. DESIGN: We measured carotid intima-media thickness (cIMT) and assessed carotid plaques by ultrasonography along with classical CV risk factors in 54 acromegaly patients (34 females, 50 ± 12 years and compared those with 62 (42 females, 53 ± 13 years) age-, sex- and CV risk factors- matched controls. In order to compare cIMT measurements between patients and controls we analyzed common carotid artery far wall data as well as a combined measurement result, which consisted of the mean value of the six different measurements, three at each side. RESULTS: mean ± SD serum GH and IGF-1 levels were 2.76 ± 4.65 ng/mL and 1.7 ± 1.25 x ULN, respectively, in all acromegaly patients. Age, body mass index, blood pressure, lipid levels, fasting glucose and Framingham's global cardiovascular risk score classification were similar comparing patients and controls. Combined median [IQR] cIMT measurements were similar in acromegaly patients and matched controls (0.59 [0.52-0.66] mm vs. 0.59 [0.52-0.69] mm; P = 0.872) as well as in acromegaly patients with active and controlled disease (0.59 [0.51-0.68] mm vs. 0.60 [0.54-0.68] mm; P = 0.385). No significant correlations were observed between cIMT measurements and GH (Spearman r = 0.1, P = 0.49) or IGF-1 (Spearman r = 0.13, P = 0.37) levels in patients with acromegaly. Carotid atherosclerotic plaques prevalence was similar in patients and controls (26% vs. 32%; P = 0.54) as well as in patients with active and controlled acromegaly (22% vs. 30%; P = 0.537). CONCLUSIONS: Our data suggest that GH/IGF-1 excess itself is not one of the main drivers of subclinical morphological atherosclerosis changes in patients with acromegaly and that optimal control of acromegaly-associated CV risk factors may preserve vasculature structure even when strict biochemical control is not achieved.