Non-resistant Patients Research Articles

Predicting monotherapy resistance risk in patients with low-risk gestational trophoblastic neoplasia: integration of the systemic immune-inflammation index and the prognostic nutritional index.

Currently, there are no reliable indicators for the early identification of patients with low-risk gestational trophoblastic neoplasia (GTN) who develop resistance to monotherapy. This study aimed to evaluate the effectiveness of combining the Systemic Immune-Inflammation Index (SII) and Prognostic Nutritional Index (PNI) in detecting early resistance to monotherapy in patients with low-risk GTN. This retrospective study included 91 patients with low-risk GTN who received initial monotherapy at Fujian Maternal and Child Health Hospital between 2013 and 2021. The SII and PNI before chemotherapy were calculated from prechemotherapy peripheral blood samples, with cut-off values determined by receiver operating characteristic (ROC) curves. The SII-PNI score ranged from 0 to 2 points and was categorized as follows: a score of 2 points indicated a high SII (≥467.02) and a low PNI (≤51.35); a score of 1 point indicated either a high SII or a low PNI; and a score of 0 points indicated neither a high SII nor a low PNI. Ninety-one patients with low-risk GTN underwent monotherapy, 19 of whom developed resistance, whereas the remaining 72 did not. The SII was significantly greater in chemotherapy-resistant patients than in non-resistant patients (P=0.04), whereas the PNI was markedly lower in chemotherapy-resistant patients (P=0.002). Univariate analysis revealed that cut-off values of 467.02 for the SII (P=0.04) and 51.35 for the PNI (P=0.024) were associated with chemotherapy resistance in patients with low-risk GTN. As the SII-PNI score increased, the proportion of chemotherapy-resistant patients increased (P<0.001), and the time for human chorionic gonadotropin (hCG) normalization correspondingly increased (P<0.001). Multivariate logistic regression analysis indicated that a high SII-PNI score is an independent risk factor for chemotherapy resistance in patients with low-risk GTN (P=0.001). A high SII and low PNI are linked to chemotherapy resistance in patients with low-risk GTN. The pretreatment SII-PNI score is a key indicator for predicting the sensitivity of patients with low-risk GTN to single-agent chemotherapy, aiding in the early identification of individuals at high risk of resistance.

Assessment of Changes in Functional Brain Connectivity During Depression Treatment with TMS Using Granger Causality Based Methods

Directed transfer function (DTF) method was used to assess brain connectivity disturbances in depression. The results were depicted as a brain model with the electroencephalographic (EEG) registration points, through which the directions of bioelectric activity transfer are defined. Transcranial magnetic stimulation (TMS) is used as an alternative treatment for drug-resistant depression and is considered to restore impaired connections. The combination of TMS and EEG allows to study changes of functional brain connectivity (FBC) in a non-invasive way. It was found that the FBC of resistant patients differed more from that of healthy subjects than in non-resistant patients. The largest changes in connectivity were identified in theta frequency.

Effectiveness of atorvastatin on the levels of nitric oxide and serum lipids in coronary artery disease patients: Response to clopidogrel resistance

Introduction and aim: Lipid lower drugs have been widely used to prevent atherosclerosis in patients with heart disease. This study aims to compare the findings between the efficacy of 20 mg/day and 40 mg/day atorvastatin supplementation for 16 weeks, on nitric oxide level and lipid profile in clopidogrel resistant and non-resistant patients with coronary heart disease (CAD). Methods: This retrospective study included two hundred and eighty-four participants with CAD. Patients were subjected to platelets function to determine the clopidogrel resistance. 88 patients were included into the clopidogrel resistant group, and 196 patients were included into the clopidogrel non-resistant group. Each group was subdivided into two subgroups depending on the daily dose of atorvastatin therapy (daily intake of 20 mg and 40 mg, orally). Results: Irrelevant to the study group, there was significant increase in serum levels of NO following 40 mg/day clopidogrel supplementation for 16 weeks as compared to 20 mg/day clopidogrel supplementation, P ≤ 0.05. This was associated with a significant reduction in serum lipids (total cholesterol and LDL-C), P ≤ 0.05. Conclusion: Atorvastatin supplementation improves serum nitric oxide level, and serum lipid profile in patients with CAD with and without clopidogrel resistance.

Factors associated with resistance to SARS-CoV-2 infection discovered using large-scale medical record data and machine learning.

There have been over 621 million cases of COVID-19 worldwide with over 6.5 million deaths. Despite the high secondary attack rate of COVID-19 in shared households, some exposed individuals do not contract the virus. In addition, little is known about whether the occurrence of COVID-19 resistance differs among people by health characteristics as stored in the electronic health records (EHR). In this retrospective analysis, we develop a statistical model to predict COVID-19 resistance in 8,536 individuals with prior COVID-19 exposure using demographics, diagnostic codes, outpatient medication orders, and count of Elixhauser comorbidities in EHR data from the COVID-19 Precision Medicine Platform Registry. Cluster analyses identified 5 patterns of diagnostic codes that distinguished resistant from non-resistant patients in our study population. In addition, our models showed modest performance in predicting COVID-19 resistance (best performing model AUROC = 0.61). Monte Carlo simulations conducted indicated that the AUROC results are statistically significant (p < 0.001) for the testing set. We hope to validate the features found to be associated with resistance/non-resistance through more advanced association studies.

PS-C33-1: CIRCADIAN RHYTHM DISTURBANCES AND BLOOD PRESSURE LEVELS IN OBESE PATIENTS WITH TRUE AND PSEUDO-RESISTANT HYPERTENSION

Background: The aim was to conduct a comparative assessment of the circadian rhythm (CR) abnormalities and blood pressure (BP) levels between pseudo- and true resistant hypertension (RH) in obesity. Methods: The study included 302 patients with uncontrolled hypertension and obesity. Initial treatment efficacy was assessed 3 months after dual therapy was administered. Those patients who did not reach target BP in dual therapy were transferred to triple therapy. Among patients who received triple therapy, 69 people did not reach target BP. All patients were additionally examined 6 months after the therapy initiation. Results: In the absence of a difference in BP levels, patients who subsequently become resistant, already at the stage of inclusion, significantly more often had a violation of CR with a predominance of the non-dipper rhythm. After 3 months of follow-up, there was a significant difference in the indicators of both office and out-of-office BP in resistant and non-resistant patients; however, the distribution of CR remained the same as at the stage of inclusion in the study. Despite the achievement of target BP after 6 months of therapy, in the majority (91.42%) of patients without resistance, the circadian rhythm normalized, while resistant patients had a normal CR only in 60.87%. At the stage of enrolling patients into the study and 3 months after the start of therapy there was no significant difference in BP levels between true and pseudo-resistance, then after 6 months of therapy, patients with true resistance had significantly higher office SBP (p &lt; 0.01) and 24 h average SBP according to ABPM data (p &lt; 0.05) compared with pseudo-resistant patients. Already at the stage of inclusion in the study, the normal CR in patients with true resistance was significantly less common than in patients with pseudo-resistance, and during the prescribed therapy, a similar trend persisted: after 6 months of antihypertensive therapy, 71.05% of pseudo-resistant patients had a normal CR, while with true resistance only about half of the patients had a normal CR. Conclusions: Even when target BP levels in antihypertensive therapy are achieved, obese patients with resistant hypertension are characterized by more pronounced disturbances of CR (most often in the form of non-dipper) and higher levels of office and out-of-office BP, compared with non-resistant patients. Compared with pseudo-resistant patients, the presence of true resistance in obesity is associated with higher SBP levels and a higher incidence of CR disturbances.

CUL4B increases platinum-based drug resistance in colorectal cancer through EMT: A study in its mechanism.

Platinum-based chemotherapy drugs play a very important role in the treatment of patients with advanced colorectal cancer, but the drug resistance of platinum-based chemotherapy drugs is an important topic that puzzles us. If we can find mechanisms of resistance, it will be revolutionary for us. We analysed the differential genes, core genes and their enrichment pathways in platinum-resistant and non-resistant patients through a public database. Platinum-resistant cell lines were cultured in vitro for in vitro colony and Transwell analysis. Tumorigenesis analysis of nude mice in vivo. Verify the function of core genes. Through differential gene and enrichment analysis, we found that CUL4B was the main factor affecting platinum drug resistance and EMT. Our hypothesis was further verified by in vitro drug-resistant and wild-type cell lines and in vivo tumorigenesis analysis of nude mice. CUL4B leads to platinum drug resistance in colorectal cancer by affecting tumour EMT.

PSUN115 Features of Metabolic and Hemodynamic Parameters in Obese Patients with True and Pseudo-Resistant Hypertension

Abstract Given the negative contribution of obesity-associated metabolic disorders to the formation of cardiovascular complications, adequate blood pressure (BP) control is very important in patients with arterial hypertension (AH) and obesity comorbidity. Objective to conduct a comparative assessment between metabolic and hemodynamic parametersinobese patients with true and pseudo-resistant AH. Methods The study included 302 patients with uncontrolled AH and obesity. Initial treatment efficacy was assessed 3 months after dual therapy was administered. Those patients who did not reach target BP in dual therapy were transferred to triple therapy. Among patients who received triple therapy, 69 people did not reach target BP (they received the fourth drug spironolactone). All patients were additionally examined 6 months after the initiation of antihypertensive therapy. Results A comparative assessment of BP levels was carried out between non-resistant and resistant patients: at the initial stage of enrolling patients, there was no significant difference in BP between non-resistant and subsequently resistant patients; after 3 months of follow-up (after prescribing double fixed combinations), there was a significant difference in the indicators of both office and out-of-office BP in resistance and non-resistance; despite the achievement of target BP levels after 6 months of therapy, in the presence of resistance, both office, home and most ABPM indicators were significantly higher than in non-resistance. An assessment of the possible causes of pseudo-resistance showed that most often, pseudo-resistance was observed in patients with non-compliance with recommendations to increase physical activity (55.26%) and reduce the calorie intake of food consumed (44.77%), as well as with poor compliance to the prescribed therapy (42.11%). At the same time, high salt intake, chronic kidney disease, obstructive sleep apnoea, and the white-coat phenomenon also contributed to the formation of pseudo-resistance. More than half of the patients (63.16%) had a combination of several factors that could contribute to the formation of pseudo-resistance. If at the stage of enrolling patients into the study and 3 months after the start of therapy there was no significant difference in BP levels between true and pseudo-resistant patients, then after 6 months of antihypertensive therapy, patients with true resistance had significantly higher levels of office SBP (p&amp;lt;0.01) and 24 h average SBP according to ABPM data (p&amp;lt;0.05) compared with pseudo-resistant patients. Obese patients with true resistance had also significantly lower BMI and LDL-cholesterol (p&amp;lt;0.05) as well as higher levels of aldosterone and SBP (p&amp;lt;0.05) compared with pseudo-resistance. Conclusions Even when target BP levels in antihypertensive therapy are achieved, obese resistant patients are characterized by higher levels of office and out-of-office BP, compared with non-resistance. Compared with pseudo-resistance, the presence of true resistance in obesity is associated with higher SBP and aldosteron levels, as well as lower BMI and LDL-cholesterol. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Importance of immunometabolic markers for the classification of patients with major depressive disorder using machine learning

BackgroundAlthough there is scientific evidence of the presence of immunometabolic alterations in major depression, not all patients present them. Recent studies point to the association between an inflammatory phenotype and certain clinical symptoms in patients with depression.The objective of our study was to classify major depression disorder patients using supervised learning algorithms or machine learning, based on immunometabolic and oxidative stress biomarkers and lifestyle habits. MethodsTaking into account a series of inflammatory and oxidative stress biomarkers (C-reactive protein (CRP), tumor necrosis factor (TNF), 4-hydroxynonenal (HNE) and glutathione), metabolic risk markers (blood pressure, waist circumference and glucose, triglyceride and cholesterol levels) and lifestyle habits of the participants (physical activity, smoking and alcohol consumption), a study was carried out using machine learning in a sample of 171 participants, 91 patients with depression (71.42% women, mean age = 50.64) and 80 healthy subjects (67.50% women, mean age = 49.12).The algorithm used was the support vector machine, performing cross validation, by which the subdivision of the sample in training (70%) and test (30%) was carried out in order to estimate the precision of the model.The prediction of belonging to the patient group (MDD patients versus control subjects), melancholic type (melancholic versus non-melancholic patients) or resistant depression group (treatment-resistant versus non-treatment-resistant) was based on the importance of each of the immunometabolic and lifestyle variables. ResultsWith the application of the algorithm, controls versus patients, such as patients with melancholic symptoms versus non-melancholic symptoms, and resistant versus non-resistant symptoms in the test phase were optimally classified.The variables that showed greater importance, according to the results of the area under the ROC curve, for the discrimination between healthy subjects and patients with depression were current alcohol consumption (AUC = 0.62), TNF-α levels (AUC = 0.61), glutathione redox status (AUC = 0.60) and the performance of both moderate (AUC = 0.59) and vigorous physical exercise (AUC = 0.58). On the other hand, the most important variables for classifying melancholic patients in relation to lifestyle habits were past (AUC = 0.65) and current (AUC = 0.60) tobacco habit, as well as walking routinely (AUC = 0.59) and in relation to immunometabolic markers were the levels of CRP (AUC = 0.62) and glucose (AUC = 0.58).In the analysis of the importance of the variables for the classification of treatment-resistant patients versus non-resistant patients, the systolic blood pressure (SBP) variable was shown to be the most relevant (AUC = 0.67). Other immunometabolic variables were also among the most important such as TNF-α (AUC = 0.65) and waist circumference (AUC = 0.64). In this case, sex (AUC = 0.59) was also relevant along with alcohol (AUC = 0.58) and tobacco (AUC = 0.56) consumption. ConclusionsThe results obtained in our study show that it is possible to predict the diagnosis of depression and its clinical typology from immunometabolic markers and lifestyle habits, using machine learning techniques. The use of this type of methodology could facilitate the identification of patients at risk of presenting depression and could be very useful for managing clinical heterogeneity.

Colchicine resistance: Associated factors and its effect on health-related quality of life in patients with familial Mediterranean fever.

To determine the factors associated with colchicine resistance and the effect of colchicine resistance on health-related quality of life (QoL) in patients with familial Mediterranean fever (FMF). Demographic and clinical features, MEFV gene mutations, and Pras disease severity scores were recorded. QoL was assessed using the Short Form-36 (SF-36) and FMF-QoL scales. Colchicine resistance was defined as at least 1 attack per month for 6months at the maximum tolerated dose of colchicine in fully compliant patients. The mean age of 118 patients (90 female, 28 male) with FMF was 38.4 ± 12.5 years. The percentage of colchicine-resistant patients was 19.5%. In univariable analysis, smoking (odds ratio [OR]=2.885; 95% confidence interval [CI]=1.104-7.539; P=0.031), attack duration (OR=1.955; 95% CI=1.137-3.360; P=0.015), presence of arthritis (OR=5.235; 95% CI=1.508-18.179; P=0.009), and disease severity score (OR=1.790; 95% CI=1.334-2.402; P < 0.001) were associated with colchicine resistance. The FMF-QoL and subscales of SF-36 except for role emotional and vitality, were different between colchicine-resistant and non-resistant patients (P < 0.05). Smoking, attack duration, presence of arthritis, and disease severity were associated with colchicine resistance in fully compliant FMF patients. Colchicine-resistant patients had poorer health-related QoL.

Different faces of resistant hypertension in obesity

Background: The aim was to conduct a comparative assessment between pseudo-resistant (due to different causes) and true resistant hypertension (RH) in obesity. Material and methods: The study included 302 patients with uncontrolled hypertension and obesity. Initial treatment efficacy was assessed 3 months after dual therapy was administered. Those patients who did not reach target blood pressure (BP) with dual therapy were switched to triple therapy. Among patients who received triple therapy, 69 people did not reach target BP (they received the fourth drug, spironolactone). All patients were additionally examined 6 months after the initiation of antihypertensive therapy. Results: Despite the achievement of target BP after 6 months of therapy, patients with resistant hypertension had significantly higher BP and more pronounced disturbances of the circadian rhythm compared with non-resistant patients. After 6 months of therapy, patients with true resistance had significantly higher SBP compared with pseudo-resistant patients. The normal circadian rhythm in patients with true resistance was significantly less common than in patients with pseudo-resistance. Compared with pseudo-resistance, the presence of true resistance in obesity was associated with higher SBP and aldosterone levels, as well as lower body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C). Conclusions: Even when target BP levels in antihypertensive therapy are achieved, obese resistant patients are characterized by more pronounced disturbances of the circadian rhythm and higher levels of office and out-of-office BP, compared with non-resistant patients. New data were obtained in the difference in the systolic blood pressure (SBP) levels (significantly higher with true resistance) and LDL-C (significantly lower with true resistance).

DISTURBANCES OF THE CIRCADIAN RHYTHM AND BLOOD PRESSURE LEVELS IN OBESE PATIENTS WITH TRUE AND PSEUDO-RESISTANT HYPERTENSION

Objective: The aim was to conduct a comparative assessment of the circadian rhythm abnormalities and blood pressure (BP) levels between pseudo-resistant and true resistant hypertension (RH) in obesity. Design and method: The study included 302 patients with uncontrolled hypertension and obesity. Initial treatment efficacy was assessed 3 months after dual therapy was administered. Those patients who did not reach target BP in dual therapy were transferred to triple therapy. Among patients who received triple therapy, 69 people did not reach target BP. All patients were additionally examined 6 months after the initiation of antihypertensive therapy. Results: In the absence of a difference in BP, patients who subsequently become resistant, already at the stage of inclusion, significantly more often had a violation of the circadian rhythm with a predominance of the non-dipper rhythm. Despite the achievement of target BP after 6 months of therapy, in the majority (91.42%) of patients without resistance, the circadian rhythm normalized, while resistant patients had a normal circadian rhythm only in 60.87%. At the stage of enrolling patients into the study and 3 months of therapy there was no significant difference in BP between true and pseudo-resistance, then after 6 months of therapy, patients with true resistance had significantly higher office SBP (p &lt; 0.01) and 24 h average SBP according to ABPM data (p &lt; 0.05) compared with pseudo-resistant patients. Already at the stage of inclusion in the study, the normal circadian rhythm in true resistance was significantly less common than in pseudo-resistance; during the prescribed therapy, a similar trend persisted: after 6 months of therapy, 71.05% of pseudo-resistant patients had a normal circadian rhythm, while with true resistance only about half of the patients had a normal circadian rhythm. Conclusions: Even when target BP levels in antihypertensive therapy are achieved, obese patients with RH are characterized by more pronounced disturbances of the circadian rhythm (most often non-dipper) and higher levels of office and out-of-office BP, compared with non-resistant patients. Compared with pseudo-resistant patients, the presence of true resistance in obesity is associated with higher SBP levels and a higher incidence of circadian rhythm disturbances.

The relationship between visual dysfunction and cognitive deficit in schizophrenia

To investigate whether visual processing abnormalities are the result of visual dysfunction involving cognitive impairment or independent abnormalities and to identify the relationship of visual impairments with cognitive functions and severity of psychopathological symptoms. We compared results of visual size perception and actions on objects (motor assessment) in patients with schizophrenia (n=37), including patients with non-resistant schizophrenia (n=19) and healthy individuals (n=20). Cognitive impairments were assessed with BACS. Severity of schizophrenia symptoms was assessed with PANSS. The error in the visual size perception test was smaller in healthy controls compared with non-resistant patients (p<0.03). There are no significant differences between non-resistant patients and other groups. Also, there are no significant differences in motor assessment between healthy controls and patients with schizophrenia. In the visual size perception test, the amount of error correlates with cognitive impairments (r= -0.84, p<0.001), and the severity of psychotic symptoms on PANSS (r=0.55, p<0.05). Changes in visual threshold in patients with schizophrenia are correlated with cognitive dysfunction and reflect dysfunction in the parvocellular system.

Biochemical aspirin resistance in acute stroke patients and its association with clinical factors: aprospective pilot study.

Aspirin is still widely used in treatment and prevention of cardiovascular diseases. To predict which patients cannot benefit from aspirin due to aspirin resistance remains agreat clinical challenge. Fifty one acute stroke/transient ischemic attack (TIA) patients (ASG) with ahistory of regular aspirin intake for the previous 7 days or more were included to the study within 24 hours of symptoms onset. Twenty nine patients admitted to our department for other reasons were the controls (CG). Each patient underwent routine blood tests (white blood cells, platelets, total cholesterol, C-reactive protein) and additional blood test: glycated haemoglobin (HbA1c), insulin, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP). Biochemical aspirin resistance was measured using the VerifyNow Aspirin platelet function analyzer. There were 9 aspirin resistance patients in ASG (17.5%) and 3 in CG (10.3%) (p = 0.38). There were no differences in either age or gender between those groups. Twelve aspirin-resistant patients differed from aspirin nonresistant patients in age, NT-proBNP and total cholesterol levels (univariate model, p = 0.004, 0.04, 0.02, respectively). In amultivariate model patients aged 76 years and more would likely to be aspirin resistant with odds ratio = 9 (95% confidence interval: 1-78). Patients aged 76 and more can be more likely aspirin resistant than younger patients. We believe that especially in the elderly with congestive heart failure there is astrong need for further investigations in this field, including searching for alternative antiplatelet therapies.

Comparison of risk scores for predicting intravenous immunoglobulin resistance in Taiwanese patients with Kawasaki disease

Kawasaki disease (KD) is the most common type of acquired heart disease in children, and intravenous immunoglobulin (IVIG) therapy is the preferred treatment. Several risk scoring systems have been developed to predict IVIG resistance, which is important in KD management, including the Kobayashi, Egami, and Formosa scores. We evaluated the performance of these scoring systems with a KD patient cohort from Taiwan. We retrospectively analyzed the medical records of all KD patients admitted to our institution from 2012 to 2017. We compared the characteristics of IVIG-resistant and non-resistant patients and evaluated the predictive ability of the scoring systems for IVIG resistance. We included 84 patients, with 73 receiving IVIG therapy. Eight patients were unresponsive to the first IVIG course. Compared to those with good response to therapy or spontaneous improvement, IVIG-resistant patients had a higher C-reactive protein level (16.1mg/dL vs. 8.6mg/dL, p<0.001), higher percentage of segmented leukocytes (75.7% vs. 61.7%, p=0.008), and lower albumin level (2.98mg/dL vs. 3.78mg/dL, p=0.001). In determining IVIG resistance, the sensitivity and specificity varied among scoring systems (Kobayashi, 37.5% and 86.8%; Egami, 37.5% and 84.2%; and Formosa, 87.5% and 73.7%, respectively). The positive and negative predictive values of the Formosa score were 25.9% and 98.2%, respectively. The Formosa score had the highest sensitivity in determining IVIG resistance. Although the positive predictive value was low, the negative predictive value could reach 98.2%. The Formosa score was superior to other scoring systems in predicting IVIG resistance in Taiwanese KD patients.

Circulating Exosomal CircMYC Is Associated with Recurrence and Bortezomib Resistance in Patients with Multiple Myeloma

Objective:Studies have shown that serum circRNA can be used as a biomarker for many tumors. However, the role of exosomal circRNA in prognostic evaluation in patients with multiple myeloma (MM) remains unclear. In this study, we aimed to analyze the role of circulating exosomal circMYC in the relapse and prognosis of patients with MM.Materials and Methods:Circulating exosomes from 122 patients with MM and 54 healthy people were isolated. Quantitative polymerase chain reaction was performed to measure circMYC exosomal expression. Kaplan-Meier survival curves with log-rank testing were used for estimating significance in survival rates. A Cox regression model was used for univariate and multivariate analysis.Results:Compared with healthy people, the expression level of serum exosomal circMYC was significantly increased in patients with MM. In addition, the expression of circMYC in circulating exosomes in bortezomib-resistant patients was significantly higher than that in non-resistant patients. The expression level of exosomal circMYC was correlated with deletion 17p, t(4;14), Durie-Salmon staging, and the International Staging System. Univariate and multivariate Cox regression analysis found that a high exosomal circMYC level was an independent predictor of poor prognosis in patients with MM. The patients with high exosome circMYC expression had higher relapse rates and higher mortality rates. The overall survival rate and progression-free survival rate of MM patients with high exosomal circMYC expression were lower than those of patients with low exosomal circMYC expression.Conclusion:These findings suggest that circulating exosomal circMYC has great potential as a biomarker for the diagnosis and prognosis of MM.

Evaluation of affective temperaments and arterial stiffness in different hypertension phenotypes.

Affective temperaments (depressive, anxious, irritable, hyperthymic, and cyclothymic) are stable parts of personality and describe emotional reactivity to external stimuli. Their relation to psychopathological conditions is obvious, but less data are available on their relationship with cardiovascular disorders. The aim of this study was to evaluate affective temperaments and hemodynamic and arterial stiffness parameters in healthy subjects (Cont), in white-coat hypertensive (WhHT) patients, and in non-resistant (non-ResHT) and resistant hypertensive (ResHT) patients. In this cross-sectional study, 363 patients were included: 82 Cont, 44 WhHT, 200 non-ResHT, and 37 ResHT. The patients completed the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A), and arterial stiffness was examined with tonometry (PulsePen). Significant differences were found between the Cont, WhHT, non-ResHT and ResHT groups in pulse wave velocity (7.76 ± 0.96, 8.13 ± 1.39, 8.98 ± 1.25, and 10.18 ± 1.18 m/s, respectively, p < 0.05 between Cont and non-ResHT/ResHT; p < 0.05 between non-ResHT and ResHT). Cyclothymic affective temperament points (4 (2.25-8)) were higher (p < 0.05) in the ResHT group than in the Cont (2 (0-5)) and non-ResHT (3 (1-5)) groups. The cyclothymic temperament points of the WhHT group (4 (2-7)) were also higher than those in the Cont group. ResHT was independently associated with a cyclothymic scale score above 6 (beta = 2.59 (95% CI: 1.16-5.77)), an irritable scale score above 7 (beta = 3.17 (95% CI: 1.3-7.69)) and an anxious scale score above 9 (beta = 2.57 (95% CI: 1.08-6.13)) points. WhHT was also independently associated with cyclothymic scale scores above 6 points (beta = 2.378, 95% CI: 1.178-4.802). In conclusion, white-coat and ResHT patients have specific affective temperament patterns, and the evaluation of these patterns can help to understand the psychopathological background of these conditions.

Dealing with heterogeneity of cognitive dysfunction in acute depression: a clustering approach.

Heterogeneity in cognitive functioning among major depressive disorder (MDD) patients could have been the reason for the small-to-moderate differences reported so far when it is compared to other psychiatric conditions or to healthy controls. Additionally, most of these studies did not take into account clinical and sociodemographic characteristics that could have played a relevant role in cognitive variability. This study aims to identify empirical clusters based on cognitive, clinical and sociodemographic variables in a sample of acute MDD patients. In a sample of 174 patients with an acute depressive episode, a two-step clustering analysis was applied considering potentially relevant cognitive, clinical and sociodemographic variables as indicators for grouping. Treatment resistance was the most important factor for clustering, closely followed by cognitive performance. Three empirical subgroups were obtained: cluster 1 was characterized by a sample of non-resistant patients with preserved cognitive functioning (n = 68, 39%); cluster 2 was formed by treatment-resistant patients with selective cognitive deficits (n = 66, 38%) and cluster 3 consisted of resistant (n = 23, 58%) and non-resistant (n = 17, 42%) acute patients with significant deficits in all neurocognitive domains (n = 40, 23%). The findings provide evidence upon the existence of cognitive heterogeneity across patients in an acute depressive episode. Therefore, assessing cognition becomes an evident necessity for all patients diagnosed with MDD, and although treatment resistant is associated with greater cognitive dysfunction, non-resistant patients can also show significant cognitive deficits. By targeting not only mood but also cognition, patients are more likely to achieve full recovery and prevent new relapses.

18F]Atorvastatin: synthesis of a potential molecular imaging tool for the assessment of statin-related mechanisms of action

BackgroundStatins are lipid-lowering agents that inhibit cholesterol synthesis and are clinically used in the primary and secondary prevention of cardiovascular diseases. However, a considerable group of patients does not respond to statin treatment, and the reason for this is still not completely understood. [18F]Atorvastatin, the 18F-labeled version of one of the most widely prescribed statins, may be a useful tool for statin-related research.Results[18F]Atorvastatin was synthesized via an optimized ruthenium-mediated late-stage 18F-deoxyfluorination. The defluoro-hydroxy precursor was produced via Paal-Knorr pyrrole synthesis and was followed by coordination of the phenol to a ruthenium complex, affording the labeling precursor in approximately 10% overall yield. Optimization and automation of the labeling procedure reliably yielded an injectable solution of [18F]atorvastatin in 19% ± 6% (d.c.) with a molar activity of 65 ± 32 GBq·μmol−1. Incubation of [18F]atorvastatin in human serum did not lead to decomposition. Furthermore, we have shown the ability of [18F]atorvastatin to cross the hepatic cell membrane to the cytosolic and microsomal fractions where HMG-CoA reductase is known to be highly expressed. Blocking assays using rat liver sections confirmed the specific binding to HMG-CoA reductase. Autoradiography on rat aorta stimulated to develop atherosclerotic plaques revealed that [18F]atorvastatin significantly accumulates in this tissue when compared to the healthy model.ConclusionsThe improved ruthenium-mediated 18F-deoxyfluorination procedure overcomes previous hurdles such as the addition of salt additives, the drying steps, or the use of different solvent mixtures at different phases of the process, which increases its practical use, and may allow faster translation to clinical settings. Based on tissue uptake evaluations, [18F]atorvastatin showed the potential to be used as a tool for the understanding of the mechanism of action of statins. Further knowledge of the in vivo biodistribution of [18F]atorvastatin may help to better understand the origin of off-target effects and potentially allow to distinguish between statin-resistant and non-resistant patients.

Association of the genetic ancestry with resistant hypertension in the ReHOT (Resistant Hypertension Optimal Treatment) randomized study

Resistant hypertension (RH) is defined as uncontrolled blood pressure despite treatment with three or more antihypertensive medications, including, if tolerated, a diuretic in adequate doses. It has been widely known that race is associated with blood pressure control. However, intense debate persists as to whether this is solely explained by unadjusted socioeconomical variables or genetic variation. In this scenario, the main aim was to evaluate the association between genetic ancestry and resistant hypertension in a large sample from a multicenter trial of stage II hypertension, the ReHOT study. Samples from 1,358 patients were analyzed, of which 167 were defined as resistant hypertensive. Genetic ancestry was defined using a panel of 192 polymorphic markers. The genetic ancestry was similar in resistant (52.0% European, 36.7% African and 11.3% Amerindian) and nonresistant hypertensive patients (54.0% European, 34.4% African and 11.6% Amerindian) (p > 0.05). However, we observed a statistically suggestive association of African ancestry with resistant hypertension in brown patient group. In conclusion, increased African genetic ancestry was not associated with RH in Brazilian patients from a prospective randomized hypertension clinical trial.

The effect of single nucleotide polymorphisms of STAT3 on epilepsy in children.

To investigate the effect of single nucleotide polymorphisms (SNPs) of signal transducer and activator of transcription 3 (STAT3) on epilepsy in children. A total of 169 children suffering from epilepsy admitted in No. 1 People's Hospital of Jining from July 2015 to December 2016 were enrolled as the research subjects. Immunohistochemistry and real time-PCR were used for analysis of the expression of STAT3 and p-STAT3 in epilepsy patients. The genotypes and alleles of rs1053005 and re744166 were analyzed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Statistical analysis was conducted to explore the correlation between the polymorphism of STAT3 and the incidence of epilepsy in children, and the polymorphism of STAT3 in the drug-resistant and non-resistant patients was compared. Both the STAT3 and p-STAT3 were over-expressed in epilepsy patients. The GG genotype of rs1053005 was significantly lower in epilepsy patients than that of health control, p<0.05. By contrast, no significant difference was found in genotypes of rs744166 between epilepsy and healthy children. When comparing the genotypes of drug-resistant patients and that of non-resistant patients, the distribution of rs1053005 genotypes in the two groups showed a significant difference, p<0.05. No statistical difference was observed in rs744166 genotypes. STAT3 polymorphism was associated with the risk of epilepsy and drug resistance to epilepsy. This study may provide a better understanding of STAT3 in epilepsy patients and provide new targets for the treatment of epilepsy patients.