Teleguidance for Patient Self-Imaging of Hemophilic Joints Using Mobile Ultrasound Devices: A Pilot Study.

BACKGROUND: Teleguidance on portable devices opens the possibility of joint self-imaging in persons with hemophilia (PWH). AIMS: Determine the feasibility of patient self-imaging with/without teleguidance. METHODS: Adult PWH received ultrasound teaching including 11 views for hemarthrosis detection in ankles, elbows, and knees. The patients acquired five randomly selected views with the Butterfly/IQ probe without assistance at 2, 6-8 weeks, and 3-4 months later, followed by teleguidance. Image acquisition was timed, patients identified anatomic landmarks, and image quality was graded. Questionnaires assessed the imaging experience. Hemophilia Joint Health Score (HJHS) indicated arthropathy status. RESULTS: Of 132 PWH, 10 (median age 52 years) opted for study inclusion. Most had severe Hemophilia A, were white/non-Hispanic, with at least a high school degree and, overall, similar to the other 122 PWH. At 2 and 6 weeks after training, ~80% images were acquired correctly compared with 53% at 12 weeks. Accuracy of landmark recognition was ~55%. With teleguidance, all images were acquired correctly, with near-perfect image quality (P ≤ .01 compared with the 3-4 month time point). Median HJHS of scanned joints was 11.5 at each time point, demonstrating a similar spectrum of arthropathic changes. Median time of image acquisition was fast, and similar with or without teleguidance (median 01:04 [mm:ss] vs median 01:02), but differed slightly between arthropathic and non-arthropathic joints. Study participants and the imaging facilitator rated that it was easy to navigate mobile technology and acquire images with teleguidance. CONCLUSION: Mobile ultrasound with teleguidance for joint self-imaging is feasible and warrants further exploration.

Consistency of serial ultrasonographic joint tissue measurements by the Joint tissueActivity and Damage Exam (JADE) protocol in relation to hemophilic joint health parameters.

OBJECTIVES: The Joint tissueActivity and Damage Exam (JADE) is a point-of-care (POC) musculoskeletal ultrasound (MSKUS) protocol for non-radiologists to evaluate hemophilic arthopathy. Our aim was to determine the consistency of cross-sectional analyses of direct tissue measurements (JADE protocol) and clinical Hemophilia Joint Health Score [HJHS] and functional joint assessments (arc) at three clinic visits. METHODS: We prospectively studied adults (n = 44) with hemophilia (A or B) of any severity and arthropathy at 3 North American sites. We assessed HJHS, total arc, and JADE parameters (bilateral elbows, ankles, and knees) at study entry, at ≈12-18 months, and at ≈24-36 months, and used MSKUS to evaluate painful episodes between study visits. JADE measurements included osteochondral alterations, cartilage thickness, and soft tissue expansion at sentinel positions. Associations between joint HJHS and total arc with each JADE variable were examined with random intercept models. RESULTS: At each visit increasing HJHS and decreasing total arc were associated in the expected direction with increasing length of OAs and soft tissue expansion in all joints, and decreasing cartilage thickness in the knee. However, HJHS associations with cartilage thickness were U-shaped for elbow and ankle (i.e. cartilage thinning and thickening). Associations between total arc and cartilage thickness followed a similar curve. (Near) normal levels of both joint parameters (HJHS and total arc) were associated with normal ranges of cartilage thickness. JADE views were also helpful to detect hemarthrosis in association with joint pains. CONCLUSIONS: POC MSKUS applying direct tissue measurements using the JADE protocol provided reproducible cross-sectional associations with joint health outcomes on three visits. These findings advance protocol validation and enable iterative adaptations resulting in JADE protocol version 2.

Fuzzy Control Application to an Irrigation System of Hydroponic Crops under Greenhouse: Case Cultivation of Strawberries (Fragaria Vesca).

Hydroponics refers to a modern set of agricultural techniques that do not require the use of natural soil for plant germination and development. These types of crops use artificial irrigation systems that, together with fuzzy control methods, allow plants to be provided with the exact amount of nutrients for optimal growth. The diffuse control begins with the sensorization of the agricultural variables that intervene in the hydroponic ecosystem, such as the environmental temperature, electrical conductivity of the nutrient solution and the temperature, humidity, and pH of the substrate. Based on this knowledge, these variables can be controlled to be within the ranges required for optimal plant growth, reducing the risk of a negative impact on the crop. This research takes, as a case study, the application of fuzzy control methods to hydroponic strawberry crops (Fragaria vesca). It is shown that, under this scheme, a greater foliage of the plants and a larger size of the fruits are obtained in comparison with natural cultivation systems in which irrigation and fertilization are carried out by default, without considering the alterations in the aforementioned variables. It is concluded that the combination of modern agricultural techniques such as hydroponics and diffuse control allow us to improve the quality of the crops and the optimization of the required resources.

Reliability and Agreement of Ultrasonographic Measures of the Ovarian Stroma: Impact of Methodology.

OBJECTIVES: Increased ovarian stromal area (SA), stromal-to-ovarian area ratio (S/A), and echogenicity (SEcho) on ultrasonography have been proposed as diagnostic markers for polycystic ovary syndrome. Although several methods to evaluate the stroma exist, their reproducibility has not been defined which limits clinical utility. This study aimed to determine the interrater reliability and agreement of methods to evaluate SA, S/A, and SEcho. METHODS: Five raters tested 3 methods to obtain SA and S/A, and one to obtain SEcho on 30 ovarian cineloops under two imaging conditions, simulating real-time (free-choice) or offline (fixed-frame) imaging. For SA, Method 1 subtracted follicular area from the ovarian area, Method 2 involved outlining the periphery of the stroma, and Method 3 represented a hybrid approach in which central follicles were subtracted from the outlined stroma. SEcho was scored on a subjective 3-tiered scale. Intraclass correlation coefficients (ICCs) and the coefficient of variation were determined for SA and S/A, and Fleiss' kappa agreement statistics (κ) were determined for SEcho. RESULTS: Interrater reliability of SA was superior using Method 1 (ICC = 0.558 and ICC = 0.705) versus Method 2 (ICC = 0.522 and ICC = 0.230) or Method 3 (ICC = 0.429 and ICC = 0.305) under free-choice and fixed-frame imaging conditions, respectively. Interrater reliability of S/A was also moderate to poor across methods. SEcho was also not reliably assessed across raters (κ = <0.500). CONCLUSIONS: Ultrasonographic assessments of the ovarian stroma were associated with moderate to poor reproducibility. Indirect estimates of the ovarian stroma (Method 1) could be optimized to yield a reproducible approach, clarifying the clinical relevance of the stroma.

Glycan moieties in Entamoeba histolytica ubiquitin are immunodominant.

The ubiquitin-proteasome system plays a central role performing several functions to maintain parasite homeostasis. We have reported the partial characterization of N-linked glycosylation profile in E. histolytica ubiquitin (EhUb). Here we examined the immunogenicity and antigenicity of carbohydrates in EhUbiquitin. Rabbits were immunized with purified EhUbiquitin or purified recombinant rUb expressed by E. coli. Using Western Blot, we explored the immunogenicity and antigenicity of protein portion and carbohydrates moiety. Interestingly, immunized rabbits produced antibodies to both Ub glycoprotein and rUb; but antibodies against carbohydrates were immunodominant, rather than antibodies to the protein moiety of EhUbiquitin. In addition, we observed that antibodies to protein moiety are not conserved in serum unless antigen is continually administrated. Conversely, anti-Ub glycoprotein antibodies are well maintained in circulation. In humans, infection with Entamoeba histolytica induces strong IgG anti-Ub response. The human antibodies recognize both, the protein moieties and the glycosylated structure. Entamoeba histolytica ubiquitin is immunogenic and antigenic. The glycan moieties are immunodominant and induces IgG. These data open the door to use carbohydrates as potential targets for diagnose tests, drugs and vaccine to prevent this parasitic disease.

Reproductive biology and population structure of white warehou Seriolella caerulea and silver warehou Seriolella punctata in the austral zone off Chile.

Using an extensive database compiled by scientific observers aboard commercial fishing operations between 1984 and 2014, we describe the maturity and size structures of white warehou Seriolella caerulea and silver warehou Seriolella punctata from by-catch of the trawling industrial fisheries operating in the austral zone off Chile. Macroscopic maturity stages and gonadosomatic (IGS ) index show mature females throughout the year and a pronounced spawning period in both austral autumn and winter seasons, with an IGS peak in July for S. punctata and August for S. caerulea. Reproductive patterns in both species show an extended spawning season (July to September) across the area between 43 and 47° S. Length-mass relationships showed significant differences between sexes in both species, where females reach a larger size. Fork length at 50% maturity was 43.5 cm for S. caerulea and 37.2 cm for S. punctata. Female catch composition is dominated by adult fish (96% for S. caerulea and 86% for S. punctata). Currently, both species are exploited with no assessment and management-decision framework. Therefore, information regarding reproductive biology and demographic traits becomes an important baseline to ensure adequate fisheries management for both species.

Certified testosterone immunoassays for hyperandrogenaemia.

BACKGROUND: Testosterone (T) measurement in women is problematic leading to initiatives aiming to improve laboratory standardization of commercial assays. We assessed the impact on the clinical diagnosis of functional hyperandrogenic disorders of a total T immunoassay recently certified by the Centers for Diseases Control and Prevention (CDC). METHODS: We conducted a cross-sectional study including 263 consecutive adult premenopausal women presenting with functional ovarian hyperandrogenism-including polycystic ovary syndrome (PCOS)-and 73 nonhyperandrogenic female volunteers who served to define reference ranges. Total T was measured by a local routine direct radioimmunoassay and by a CDC-certified immunochemiluminescence assay. The main outcome measures were total and calculated free T concentrations and percentage of patients with hyperandrogenaemia. RESULTS: Both assays showed a poor concordance for total and calculated free T measurements. Hence, 147 (56%) and 109 (41%) of women had hyperandrogenaemia with the routine and CDC-certified assays, respectively [κ (95%CI): 0.538 (0.441-0.634)]. Free T levels calculated from total T using both assays showed similar correlations with metabolic variables. Women showing hyperandrogenaemia by both methods had the worst metabolic profiles, yet women presenting with hyperandrogenaemia only when using the CDC-certified assay did not show any significant difference compared to nonhyperandrogenic women in anthropometric or metabolic variables. Those women with hyperandrogenaemia only when using the routine assay were more obese and insulin resistant than normoandrogenaemic hirsute patients. CONCLUSIONS: An isolated androgen measurement, even a very specific one, is unlikely to identify the hyperandrogenic milieu that characterizes patients with functional ovarian hyperandrogenism and PCOS.

A Suitable HPLC-MS/MS Methodology for the Detection of Oxytetracycline, Enrofloxacin, and Sulfachloropyridazine Residues in Lettuce Plants.

Oxytetracycline (OTC), enrofloxacin (EFX), and sulfachloropyridazine (SCP) are critically important antimicrobials (AMs) in both human and veterinary medicine, where they are widely used in farm animals. Lettuce has become a matrix of choice for studying the presence of residues of these AMs in plants, as the concentrations of residues detected in lettuce can range from ng to mg. While several analytical methodologies have been developed for the purpose of detecting AMs in lettuce, these currently do not detect both the parent compound and its active metabolites or epimers, such as in the case of ciprofloxacin (CFX) and 4-epi-oxitetracycline (4-epi-OTC), which also pose a risk to public health and the environment due to their AM activity. In light of this situation, this work proposes an analytical method that was developed specifically to allow for the detection of OTC, 4-epi-OTC, EFX, CFX, and SCP in a lettuce matrix. This method uses acetonitrile, methanol, 0.5% formic acid, and McIlvaine-EDTA buffer as extraction solvents, and dispersive solid-phase extraction (dSPE) for the clean-up. The analytes were detected using a liquid chromatography technique coupled to mass spectrometry (HPLC-MS/MS). Parameters such as the specificity, linearity, recovery, precision, limit of detection, and limit (LOD) of quantification (LOQ) were calculated according to the recommendations established in the European Union decision 2021/808/EC and VICH GL2: Validation of analytical procedures. The LOQ for the analytes OTC, 4-epi-OTC, CFX, and SCP was 1 µg·kg-1, whereas for EFX, it was 5 µg·kg-1 dry weight. All calibration curves showed a coefficient of determination (R2) of >0.99. The recovery levels ranged from 93.0 to 110.5% and the precision met the acceptance criteria, with a coefficient of variation of ≤14.02%. Therefore, this methodology allows for the precise and reliable detection and quantification of these analytes. The analysis of commercial samples confirmed the suitability of this method.

Extracolonic manifestations of Gardner syndrome: A case report.

Gardner syndrome has head and neck manifestations that may be recognized during dental visits. Features such as multiple gnathic osteomas, impacted supernumerary teeth, and multiple foci of idiopathic osteosclerosis can be easily identified on dental radiographs, prompting the clinician to refer the patient for further investigation. A dental examination and routine radiographs play a vital role in revealing the extracolonic presentation of Gardner syndrome, which facilitates timely screening and detection of colorectal cancer and other malignancies associated with this condition. This report discusses the case of a 50-year-old Caucasian man who presented with a hard swelling of the left angle of the mandible and was diagnosed with Gardner syndrome based on abnormal findings from an oral examination, dental imaging, and medical and family history.

Data-Driven Personalized Care in Lung Cancer: Scoping Review and Clinical Recommendations on Performance Status and Activity Level of Patients With Lung Cancer Using Wearable Devices.

PURPOSE: Performance status (PS) is a crucial assessment for research and clinical practice in lung cancer (LC), including its usage for the assessment of the suitability and toxicity of treatment or eligibility for clinical trials of patients with LC. These PS assessments are subjective and lead to substantial discrepancies between observers. To improve the objectivity of PS assessments, Electronic Activity Monitoring devices (EAMs) are increasingly used in oncology, but how these devices are used for PS assessments in LC is an issue that remains unclear. The goal of this study is to address the challenges and opportunities of the use of digital tools to support PS assessments in patients with LC. METHODS: The literature review followed PRISMA-ScR methodology. Searches were performed in the ScienceDirect, PsycInfo, ACM, IEEE Xplore, and PubMed databases. Furthermore, a panel discussion was performed to address the clinical use cases. RESULTS: Thirty-two publications were found. Most of the studies used wrist accelerometry-based wearables (59%) and monitored sleep activity (SA; 28%) or physical activity (PA; 72%). Critical findings include positive usefulness of the use of wearables to categorize moderate-to-vigorous/light PA, which was associated with better sleep and health. In addition, steps and time awake immobile were found to be associated with risk of hospitalization and survival. Use cases identified included the health assessment of patients and clinical research. CONCLUSION: There are positive experiences in the use of EAM to complement PS assessment in LC. However, there is a need for adapting thresholds to the particularities of patients with LC, for example, differentiating moderate-to-vigorous and light. Moreover, developing methodologies combining PS assessments and the use of EAM adapted to clinical and research practice is needed.

Textural, Microstructural and Chemical Characterization of Ferritic Stainless Steel Affected by the Gold Dust Defect.

The "gold dust defect" (GDD) appears at the surface of ferritic stainless steels (FSS) and degrades their appearance. Previous research showed that this defect might be related to intergranular corrosion and that the addition of aluminium improves surface quality. However, the nature and origin of this defect are not properly understood yet. In this study, we performed detailed electron backscatter diffraction analyses and advanced monochromated electron energy-loss spectroscopy experiments combined with machine-learning analyses in order to extract a wealth of information on the GDD. Our results show that the GDD leads to strong textural, chemical, and microstructural heterogeneities. In particular, the surface of affected samples presents an α-fibre texture which is characteristic of poorly recrystallised FSS. It is associated with a specific microstructure in which elongated grains are separated from the matrix by cracks. The edges of the cracks are rich in chromium oxides and MnCr2O4 spinel. In addition, the surface of the affected samples presents a heterogeneous passive layer, in contrast with the surface of unaffected samples, which shows a thicker and continuous passive layer. The quality of the passive layer is improved with the addition of aluminium, explaining the better resistance to the GDD.

Cost-effectiveness of adjuvant atezolizumab versus best supportive care in the treatment of patients with resectable early-stage non-small cell lung cancer and overexpression of PD-L1.

AIMS: To assess the cost-effectiveness of adjuvant atezolizumab in the treatment of early-stage NSCLC patients (stage II-IIIA) with expression PD-L1 ≥ 50% without mutations in EGFR or ALK rearrangements in Spain. MATERIALS AND METHODS: A 5-states Markov model (DFS, locoregional recurrence, 1 L-metastatic recurrence, 2 L-metastatic recurrence, and death states) was adapted to the Spanish setting. Demographic characteristics of the hypothetical cohort, transition probabilities from the DFS state, and safety parameters were obtained from IMpower010 study (GO29527). Transition probabilities from locoregional and metastatic health states were obtained from the literature. The usual clinical practice in Spain (use of health resources, management of the disease, etc.) was obtained from a previous analysis carried out by the authors of this study. A societal perspective was considered so both direct and indirect costs were included (expressed in € of 2021). A lifetime horizon was used, so costs and health outcomes were discounted at 3% per year. Sensitivity analyses were performed to evaluate uncertainty. RESULTS: Over a lifetime horizon, treatment with adjuvant atezolizumab provided greater effectiveness (+2.61 life years [LY] and +1.95 quality-adjusted life years [QALY]) and higher cost (€+22,538) than BSC. The incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratios (ICUR) of the analysis were €8,625/LY gained and €11,583/QALY gained, respectively. Robustness of these base-case results was confirmed by the sensitivity analyses performed. In the probabilistic sensitivity analysis, 90% of the simulations performed showed that adjuvant atezolizumab is cost-effective versus BSC, considering a threshold of €30,000/QALY. CONCLUSIONS: Our results showed that adjuvant treatment with atezolizumab in patients with early-stage resected NSCLC with overexpression of PD-L1 and without EGFR and ALK mutations is cost-effective versus BSC as the ICERs and ICURs obtained are below the cost-effectiveness thresholds commonly considered in Spain, thus offering a new treatment alternative for these patients.

Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration following peripheral nerve injury.

Following peripheral nerve injury, successful axonal growth and functional recovery require Schwann cell (SC) reprogramming into a reparative phenotype, a process dependent upon c-Jun transcription factor activation. Unfortunately, axonal regeneration is greatly impaired in aged organisms and following chronic denervation, which can lead to poor clinical outcomes. While diminished c-Jun expression in SCs has been associated with regenerative failure, it is unclear whether the inability to maintain a repair state is associated with the transition into an axonal growth inhibition phenotype. We here find that reparative SCs transition into a senescent phenotype, characterized by diminished c-Jun expression and secretion of inhibitory factors for axonal regeneration in aging and chronic denervation. In both conditions, the elimination of senescent SCs by systemic senolytic drug treatment or genetic targeting improved nerve regeneration and functional recovery, increased c-Jun expression and decreased nerve inflammation. This work provides the first characterization of senescent SCs and their influence on axonal regeneration in aging and chronic denervation, opening new avenues for enhancing regeneration and functional recovery after peripheral nerve injuries.

Dummy regression to predict dry fiber in Agave lechuguilla Torr. in two large-scale bioclimatic regions in Mexico.

Agave lechuguilla Torr., of the family Agavaceae, is distributed from southwestern United States to southern Mexico and is one of the most representative species of arid and semiarid regions. Its fiber is extracted for multiple purposes. The objective of this study was to generate a robust model to predict dry fiber yield (Dfw) rapidly, simply, and inexpensively. We used a power model in its linear form and bioclimatic areas as dummy variables. Training, generation (80%) and validation (20%) of the model was performed using machine learning with the package 'caret' of R. Using canonical correlation analysis (CCA), we evaluated the relationship of Dwf to bioclimatic variables. The principal components analysis (PCA) generated two bioclimatic zones, each with different A. lechuguilla productivities. We evaluated 499 individuals in four states of Mexico. The crown diameter (Cd) of this species adequately predicts its fiber dry weight (R2 = 0.6327; p < 0.05). The intercept (ß0), slope [lnCd (ß1)], zone [(ß2)] and interaction [lnCd:Zona (ß3)] of the dummy model was statistically significant (p < 0.05), giving origin to an equation for each bioclimatic zone. The CCA indicates a positive correlation between minimum temperature of the coldest month (Bio 6) and Dwf (r = 0.84 and p < 0.05). In conclusion, because of the decrease in Bio 6 of more than 0.5°C by 2050, the species could be vulnerable to climate change, and A. lechuguilla fiber production could be affected gradually in the coming years.

Effect of Iron Depletion by Bloodletting vs. Observation on Oxidative Stress Biomarkers of Women with Functional Hyperandrogenism Taking a Combined Oral Contraceptive: A Randomized Clinical Trial.

Women with functional hyperandrogenism show both increased markers of oxidative stress and a mild iron overload. Combined oral contraceptives (COC) may worsen redox status in the general population. Since iron depletion ameliorates oxidative stress in other iron overload states, we aimed to address the changes in the redox status of these women as a consequence of COC therapy and of bloodletting, conducting a randomized, controlled, parallel, open-label clinical trial in 33 adult women with polycystic ovary syndrome or idiopathic hyperandrogenism. After three months of treatment with a COC, participants were randomized (1:1) to three scheduled bloodlettings or observation for another nine months. After taking a COC, participants showed a mild decrease in their plasma electrochemical antioxidant capacity, considering fast-acting antioxidants [MD: −1.51 (−2.43 to −0.60) µC, p = 0.002], and slow-acting antioxidants [MD: −1.90 (−2.66 to −1.14) µC, p < 0.001]. Women submitted to bloodletting showed a decrease in their non-enzymatic antioxidant capacity levels (NEAC) throughout the trial, whereas those individuals in the control arm showed a mild increase in these levels at the end of the study (Wilks' λ: 0.802, F: 3.572, p = 0.041). Decreasing ferritin and plasma hemoglobin during the trial were associated with worse NEAC levels. COC may impair redox status in women with functional hyperandrogenism. Decreasing iron stores by scheduled bloodletting does not override this impairment.

Iron Overload in Functional Hyperandrogenism: In a Randomized Trial, Bloodletting Does Not Improve Metabolic Outcomes.

CONTEXT: Functional hyperandrogenism may be associated with a mild increase in body iron stores. Iron depletion exerts a beneficial effect on metabolic endpoints in other iron overload states. OBJECTIVES: (i) To determine the effect of iron depletion on the insulin sensitivity and frequency of abnormal glucose tolerance in patients with functional hyperandrogenism submitted to standard therapy with combined oral contraceptives (COC). ii) To assess the overall safety of this intervention. DESIGN: Randomized, parallel, open-label, clinical trial. SETTING: Academic hospital. PATIENTS: Adult women with polycystic ovary syndrome or idiopathic hyperandrogenism. INTERVENTION: After a 3-month run-in period of treatment with 35 µg ethinylestradiol plus 2 mg cyproterone acetate, participants were randomized (1:1) to 3 scheduled bloodlettings or observation for another 9 months. MAIN OUTCOME MEASURES: Changes in insulin sensitivity index and frequency of prediabetes/diabetes, and percentage of women in whom bloodletting resulted in plasma hemoglobin <120 g/L and/or hematocrit <0.36. RESULTS: From 2015 to 2019, 33 women were included by intention-to-treat. During the follow-up, insulin sensitivity did not change in the whole group of women or between study arms [mean of the differences (MD): 0.0 (95%CI: -1.6 to 1.6)]. Women in the experimental arm showed a similar odds of having prediabetes/diabetes than women submitted to observation [odds ratio: 0.981 (95%CI: 0.712 to 1.351)]. After bloodletting, 4 (21.1%) and 2 women (10.5%) in the experimental arm had hemoglobin (Hb) levels <120 g/L and hematocrit (Hct) values <0.36, respectively, but none showed Hb <110 g/L or Hct <0.34. CONCLUSIONS: Scheduled bloodletting does not improve insulin sensitivity in women with functional hyperandrogenism on COC.

Bloodletting has no effect on the blood pressure abnormalities of hyperandrogenic women taking oral contraceptives in a randomized clinical trial.

Normoferritinemic women with functional hyperandrogenism show a mild iron overload. Iron excess, hyperandrogenism, and cardioautonomic dysfunction contribute to blood pressure (BP) abnormalities in these patients. Furthermore, combined oral contraceptives (COC) prescribed for hyperandrogenic symptoms may worse BP recordings. Iron depletion by phlebotomy appears to lower BP in other acquired iron overload conditions. We aimed to determine the effect of iron depletion on the office BP, ambulatory BP monitoring, and frequency of hypertension in patients with functional hyperandrogenism submitted to standard therapy with COC. We conducted a phase 2 randomized, controlled, parallel, open-label clinical trial (NCT02460445) in adult women with functional hyperandrogenism including hyperandrogenic polycystic ovary syndrome and idiopathic hyperandrogenism. After a 3-month run-in period of treatment with 35 µg ethinylestradiol plus 2 mg cyproterone acetate, participants were randomized (1:1) to three scheduled bloodlettings or observation for another 9 months. Main outcome measures were the changes in office BP, 24-h-ambulatory BP, and frequency of hypertension in both study arms. From June 2015 to June 2019, 33 women were included in the intention-to-treat analyses. We observed an increase in mean office systolic BP [mean of the differences (MD): 2.5 (0.3-4.8) mmHg] and night-time ambulatory systolic BP [MD 4.1 (1.4-6.8) mmHg] after 3 months on COC. The percentage of nocturnal BP non-dippers also increased, from 28.1 to 92.3% (P < 0.001). Office and ambulatory BP did not change throughout the experimental period of the trial, both when considering all women as a whole or as a function of the study arm. The frequency of the non-dipping pattern in BP decreased during the experimental period [OR 0.694 (0.577-0.835), P < 0.001], regardless of the study arm. Decreasing iron stores by scheduled bloodletting does not override the BP abnormalities caused by COC in women with functional hyperandrogenism.

A safety evaluation of current medications for adult women with the polycystic ovarian syndrome not pursuing pregnancy.

INTRODUCTION: The polycystic ovary syndrome (PCOS) is a very prevalent disorder in premenopausal women. Cardiovascular risk factors cluster in these patients, raising concern about the safety of the drugs commonly used to ameliorate symptoms of androgen excess in in this population at risk of cardiovascular morbidity. AREAS COVERED: This review summarizes the clinical efficacy and safety profiles of drugs commonly used for the management of hyperandrogenic symptoms and endometrial protection in adult women with PCOS who do not seek pregnancy. EXPERT OPINION: Antiandrogenic drugs usually used in adult women with PCOS carry a low risk of severe side effects. In spite of the cardiovascular risk profile of women with PCOS, and that individualized risk assessment is of paramount importance, there is no solid evidence supporting that the use of combined oral contraceptives in these women increases the risk of cardiovascular or thromboembolic events compared with the general population. However, virtually all these drugs are used in an off-label fashion. Large, high-quality studies addressing the long-term safety of pharmacological treatments in women with PCOS are definitely needed.

Polycystic ovary syndrome in adult women. / Síndrome de ovario poliquístico en la mujer adulta.

Polycystic ovary syndrome is the most prevalent endocrine-metabolic pathology in pre-menopausal women. Its etiopathogenesis is complex, multifactorial and heterogeneous, including the interaction of genetic, epigenetic and environmental factors. Androgenic excess constitutes the disease's main physiopathological mechanism and results in reproductive, metabolic and cosmetic alterations which negatively impact these patients' quality of life. The criteria established in the Rotterdam consensus and their correct application form the necessary basis for this syndrome's proper diagnosis. In the absence of an aetiological treatment, the aim is to improve the clinical signs and symptoms derived from hyperandrogenism, ovarian dysfunction and existing metabolic complications, and, therefore, they must be chronic and individualised.