Critical features of acute stress induced cross-sensitization identified through the hypothalamic-pituitary-adrenal axis output

Stress-induced sensitization represents a process whereby prior exposure to severe stressors leaves animals or humans in a hyper-responsive state to further stressors. Indeed, this phenomenon is assumed to be the basis of certain stress-associated pathologies, including post-traumatic stress disorder and psychosis. One biological system particularly prone to sensitization is the hypothalamic-pituitary-adrenal (HPA) axis, the prototypic stress system. It is well established that under certain conditions, prior exposure of animals to acute and chronic (triggering) stressors enhances HPA responses to novel (heterotypic) stressors on subsequent days (e.g. raised plasma ACTH and corticosterone levels). However, such changes remain somewhat controversial and thus, the present study aimed to identify the critical characteristics of the triggering and challenging stressors that affect acute stress-induced HPA cross-sensitization in adult rats. We found that HPA cross-sensitization is markedly influenced by the intensity of the triggering stressor, whereas the length of exposure mainly affects its persistence. Importantly, HPA sensitization is more evident with mild than strong challenging stressors, and it may remain unnoticed if exposure to the challenging stressor is prolonged beyond 15 min. We speculate that heterotypic HPA sensitization might have developed to optimize biologically adaptive responses to further brief stressors

Individual differences in the neuroendocrine response of male rats to emotional stressors are not trait-like and strongly depend on the intensity of the stressors

Altres ajuts: Acord transformatiu CRUE-CSICBiological response to stressors is critical to understand stress-related pathologies and vulnerability to psychiatric diseases. It is assumed that we can identify trait-like characteristics in biological responsiveness by testing subjects in a particular stressful situation, but there is scarce information on this issue. We then studied, in a normal outbred population of adult male rats (n = 32), the response of well-characterized stress markers (ACTH, corticosterone and prolactin) to different types of stressors: two novel environments (open-field, OF1 and OF2), an elevated platform (EP), forced swim (SWIM) and immobilization (IMO). Based on both plasma ACTH and prolactin levels, the OF1 was the lowest intensity situation, followed by the OF2 and the EP, then SWIM and finally IMO. When correlations between the individual responses to the different stressors were studied, the magnitude of the correlations was most dependent on the similarities in intensity rather than on other characteristics of stressors, with good correlations between similar intensity stressors and no correlations at all were found between stressors markedly differing in intensity. In two additional confirmatory experiments (n = 37 and n = 20) with HPA hormones, we observed good correlation between the response to restraint and IMO, which were close in intensity, and no correlation between OF1 and SWIM. The present results suggest that individual neuroendocrine response to a particular stressor does not predict the response to another stressor greatly differing in intensity, thus precluding characterization of low or high responsive individuals to any stressor in a normal population. The present data have important implications for human studies

Stress-induced sensitization: the hypothalamic-pituitary-adrenal axis and beyond

Exposure to certain acute and chronic stressors results in an immediate behavioral and physiological response to the situation followed by a period of days when cross-sensitization to further novel stressors is observed. Cross-sensitization affects to different behavioral and physiological systems, more particularly to the hypothalamus-pituitary-adrenal (HPA) axis. It appears that the nature of the initial (triggering) stressor plays a major role, HPA cross-sensitization being more widely observed with systemic or high-intensity emotional stressors. Less important appears to be the nature of the novel (challenging) stressor, although HPA cross-sensitization is better observed with short duration (5-15 min) challenging stressors. In some studies with acute immune stressors, HPA sensitization appears to develop over time (incubation), but most results indicate a strong initial sensitization that progressively declines over the days. Sensitization can affect other physiological system (i.e. plasma catecholamines, brain monoamines), but it is not a general phenomenon. When studied concurrently, behavioral sensitization appears to persist longer than that of the HPA axis, a finding of interest regarding long-term consequences of traumatic stress. In many cases, behavioral and physiological consequences of prior stress can only be observed following imposition of a new stressor, suggesting long-term latent effects of the initial exposure

Chimney Stenting During Transcatheter Aortic Valve Implantation

Acute coronary artery obstruction is a rare but life-threatening complication of transcatheter aortic valve implantation. In patients at risk of coronary artery obstruction, pre-emptive coronary artery protection with a coronary wire, balloon or stent provides a bailout treatment option. The authors describe the steps involved in performing chimney stenting and summarise the short- and long-term outcome data associated with this technique

Validation of the long-term assessment of hypothalamic-pituitary-adrenal activity in rats using hair corticosterone as a biomarker

The evaluation of chronic activity of the hypothalamic-pituitary-adrenal (HPA) axis is critical for determining the impact of chronic stressful situations. However, current methods have important limitations. The potential use of hair glucocorticoids as a noninvasive retrospective biomarker of long-term HPA activity is gaining acceptance in humans and wild animals. However, there is no study examining hair corticosterone (HC) in laboratory animals. The present study validates a method for measuring HC in rats and demonstrates that it properly reflects chronic HPA activity. The HC concentration was similar in male and female rats, despite higher total plasma corticosterone levels in females, tentatively suggesting that it reflects free rather than total plasma corticosterone. Exposure of male rats to 2 different chronic stress protocols (chronic immobilization and chronic unpredictable stress) resulted in similarly higher HC levels compared to controls (1.8-fold). HC also increased after a mild chronic stressor (30 min daily restraint). Chronic administration of 2 different doses of a long-acting ACTH preparation dramatically increased HC (3.1- and 21.5-fold, respectively), demonstrating that a ceiling effect in HC accumulation is unlikely under other more natural conditions. Finally, adrenalectomy significantly reduced HC. In conclusion, HC measurement in rats appears appropriate to evaluate integrated chronic changes in circulating corticosterone

Emotional responses to a negative emotion induction procedure in Borderline Personality Disorder

The aim of this study was to determine if patients with Borderline Personality Disorder (BPD) present higher emotional response than healthy controls in a laboratory setting. Fifty participants (35 patients with BPD and 15 healthy controls) underwent a negative emotion induction procedure (presentation of standardized unpleasant images). Subjective emotional responses were assessed by means of self-reported questionnaires while biological reactivity during the procedure was measured through levels of salivary cortisol (sCORT) and alpha-amylase (sAA). Patients with BPD exhibited significant lower cortisol levels and higher sAA levels compared to controls. Self-reported emotional reactivity did not give rise to differences between groups but participants with BPD did present higher levels of negative emotional intensity at baseline and during the entire procedure. The findings do not give support to the emotional hyperreactivity hypothesis in BPD. However, BPD patients presented heightened negative mood intensity at baseline, which should be considered a hallmark of the disorder. Further studies using more BPD-specific emotion inductions are needed to confirm the trends observed in this studyEl presente estudio pretende determinar si existe o no una mayor reactividad emocional en el Trastorno Límite de la Personalidad (TLP) en un contexto de laboratorio. Se realizó una inducción emocional negativa (presentación de imágenes estandarizadas con contenido negativo) a cincuenta participantes (35 pacientes con TLP y 15 controles sanos). Para evaluar la respuesta emocional subjetiva se utilizaron cuestionarios auto-informados; los niveles de cortisol (sCORT) y alfa-amilasa (sAA) salivares se utilizaron para medir la reactividad biológica al procedimiento. En el grupo de TLP, se observaron niveles de sCORT más bajos y niveles de sAA más elevados en comparación al grupo control. No se observaron diferencias significativas en relación a la reactividad emocional auto-informada, pero los pacientes con TLP reportaron mayor intensidad de emociones negativas a nivel basal así como también durante todo el procedimiento. Los resultados no apoyan la hipótesis de hiperreactividad emocional en el TLP. Sin embargo, los pacientes con TLP presentaron mayor intensidad de emociones negativas a nivel basal, característica que debería ser considerada como esencial en el trastorno. Futuros estudios deberán incorporar otros paradigmas de inducción emocional más específicos para TLP con el fin de confirmar las tendencias observadas en el presente estudi

Baseline ECG and prognosis after transcatheter aortic valve implantation: the role of interatrial block

Background: The clinical significance of conduction disturbances after transcatheter aortic valve implantation has been described; however, little is known about the influence of baseline ECGs in the prognosis of these patients. Our aim was to study the influence of baseline ECG parameters, including interatrial block (IAB), in the prognosis of patients treated with transcatheter aortic valve implantation. Methods and Results: The BIT (Baseline Interatrial Block and Transcatheter Aortic Valve Implantation) registry included 2527 patients with aortic stenosis treated with transcatheter aortic valve implantation. A centralized analysis of baseline ECGs was performed. Patients were divided into 4 groups: normal P wave duration (<120 ms); partial IAB (P wave duration ≥120 ms, positive in the inferior leads); advanced IAB (P wave duration ≥120 ms, biphasic [+/-] morphology in the inferior leads); and nonsinus rhythm (atrial fibrillation/flutter and paced rhythm). The mean age of patients was 82.6±9.8 years and 1397 (55.3%) were women. A total of 960 patients (38.0%) had a normal P wave, 582 (23.0%) had partial IAB, 300 (11.9%) had advanced IAB, and 685 (27.1%) presented with nonsinus rhythm. Mean follow‐up duration was 465±171 days. Advanced IAB was the only independent predictor of all‐cause mortality (hazard ratio [HR], 1.48; 95% CI, 1.10-1.98 [P=0.010]) and of the composite end point (death/stroke/new atrial fibrillation) (HR, 1.51; 95% CI, 1.17-1.94 [P=0.001]). Conclusions: Baseline ECG characteristics influence the prognosis of patients with aortic stenosis treated with transcatheter aortic valve implantation. Advanced IAB is present in about an eighth of patients and is associated with all‐cause death and the composite end point of death, stroke, and new atrial fibrillation during follow‐up

Impact of COVID-19 Pandemic on TAVR Activity: A Worldwide Registry

Background: The COVID-19 pandemic had a considerable impact on the provision of structural heart intervention worldwide. Our objectives were: 1) to assess the impact of the COVID-19 pandemic on transcatheter aortic valve replacement (TAVR) activity globally; and 2) to determine the differences in the impact according to geographic region and the demographic, development, and economic status of diverse international health care systems. Methods: We developed a multinational registry of global TAVR activity and invited individual TAVR sites to submit TAVR implant data before and during the COVID-19 pandemic. Specifically, the number of TAVR procedures performed monthly from January 2019 to December 2021 was collected. The adaptive measures to maintain TAVR activity by each site were recorded, as was a variety of indices relating to type of health care system and national economic indices. The primary subject of interest was the impact on TAVR activity during each of the pandemic waves (2020 and 2021) compared with the same period pre–COVID-19 (2019). Results: Data were received from 130 centers from 61 countries, with 14 subcontinents and 5 continents participating in the study. Overall, TAVR activity increased by 16.7% (2,337 procedures) between 2018 and 2019 (ie, before the pandemic), but between 2019 and 2020 (ie, first year of the pandemic), there was no significant growth (–0.1%; –10 procedures). In contrast, activity again increased by 18.9% (3,085 procedures) between 2020 and 2021 (ie, second year of the pandemic). During the first pandemic wave, there was a reduction of 18.9% (945 procedures) in TAVR activity among participating sites, while during the second and third waves, there was an increase of 6.7% (489 procedures) and 15.9% (1,042 procedures), respectively. Further analysis and results of this study are ongoing and will be available at the time of the congress. Conclusion: The COVID-19 pandemic initially led to a reduction in the number of patients undergoing TAVR worldwide, although health care systems subsequently adapted, and the number of TAVR recipients continued to grow in subsequent COVID-19 pandemic waves. Categories: STRUCTURAL: Valvular Disease: Aorti

Trends in the epidemiology of catheter-related bloodstream infections; towards a paradigm shift, Spain, 2007 to 2019

Altres ajuts: Departament de Salut. Generalitat de Catalunya ("Pla estratègic de recerca i innovació en salut (PERIS) 2019-2021"); Ministerio de Asuntos Económicos y Transformación Digital; Red Española de Investigación en Patología Infecciosa (REIPI).Background: Catheter-related bloodstream infections (CRBSI) are frequent healthcare-associated infections and an important cause of death. Aim: To analyse changes in CRBSI epidemiology observed by the Infection Control Catalan Programme (VINCat). Methods: A cohort study including all hospital-acquired CRBSI episodes diagnosed at 55 hospitals (2007-2019) in Catalonia, Spain, was prospectively conducted. CRBSI incidence rates were adjusted per 1,000patientdays. To assess the CRBSI rate trend per year, negative binomial models were used, with the number of events as the dependent variable, and the year as the main independent variable. From each model, the annual rate of CRBSI diagnosed per 1,000patientdays and the incidence rate ratio (IRR) with its 95% confidence intervals (CI) were reported. Results: During the study, 9,290 CRBSI episodes were diagnosed (mean annual incidence rate:0.20episodes/1,000patientdays). Patients' median age was 64.1years; 36.6% (3,403/9,290) were female. In total, 73.7% (n=6,845) of CRBSI occurred in non-intensive care unit (ICU) wards, 62.7% (n=5,822) were related to central venous catheter (CVC), 24.1% (n=2,236) to peripheral venous catheters (PVC) and 13.3% (n=1,232) to peripherally-inserted central venous catheters (PICVC). Incidence rate fell over the study period (IRR:0.94;95%CI:0.93-0.96), especially in the ICU (IRR:0.88;95%CI:0.87-0.89). As a whole, while episodes of CVC CRBSI fell significantly (IRR:0.88;95%CI:0.87-0.91), peripherally-inserted catheter CRBSI (PVC and PICVC) rose, especially in medical wards (IRR PICVC:1.08;95%CI:1.05-1.11; IRR PVC: 1.03; 95% 1.00-1.05). Conclusions: Over the study, CRBSIs associated with CVC and diagnosed in ICUs decreased while episodes in conventional wards involving peripherally-inserted catheters increased. Hospitals should implement preventive measures in conventional wards

Critical features of acute stress induced cross-sensitization identified through the hypothalamic-pituitary-adrenal axis output

Stress-induced sensitization represents a process whereby prior exposure to severe stressors leaves animals or humans in a hyper-responsive state to further stressors. Indeed, this phenomenon is assumed to be the basis of certain stress-associated pathologies, including post-traumatic stress disorder and psychosis. One biological system particularly prone to sensitization is the hypothalamic-pituitary-adrenal (HPA) axis, the prototypic stress system. It is well established that under certain conditions, prior exposure of animals to acute and chronic (triggering) stressors enhances HPA responses to novel (heterotypic) stressors on subsequent days (e.g. raised plasma ACTH and corticosterone levels). However, such changes remain somewhat controversial and thus, the present study aimed to identify the critical characteristics of the triggering and challenging stressors that affect acute stress-induced HPA cross-sensitization in adult rats. We found that HPA cross-sensitization is markedly influenced by the intensity of the triggering stressor, whereas the length of exposure mainly affects its persistence. Importantly, HPA sensitization is more evident with mild than strong challenging stressors, and it may remain unnoticed if exposure to the challenging stressor is prolonged beyond 15 min. We speculate that heterotypic HPA sensitization might have developed to optimize biologically adaptive responses to further brief stressors