Impact of Gene-Gender Effects of Adrenergic Polymorphisms on Hypothalamic-Pituitary-Adrenal Axis Activity in Depressed Patients

Objective: There is overwhelming evidence that activation of the hypothalamic-pituitary-adrenal (HPA) system plays a major role in depression and cardiovascular disease in genetically susceptible individuals. We hypothesized that due to the multiple interactions between the sympathetic and the HPA systems via adrenoceptors, polymorphisms in these genes could have an impact on HPA axis activity in major depression. Methods: Using the dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test, we investigated the association of alpha 2-adrenoceptor (ADRA2A -1291C -> G) and the beta 2-adrenoceptor gene (ADRB2 Arg16Gly) in 189 patients with major depression during the acute state of the disease and after remission. Results: Male ADRA2A -1291G allele homozygotes showed significant pretreatment HPA axis hyperactivity, with increased adrenocorticotropin (ACTH; F = 4.9, d.f. = 2, p = 0.009) and cortisol responses (F = 6.4, d.f. = 2, p = 0.003). In contrast, female ADRB2 Arg/Arg homozygotes had increased pretreatment ACTH (F = 7.17, d.f. = 2, p = 0.001) and cortisol (F = 8.95, d.f. = 2, p = 0.000) levels. Interestingly, in the respective genotypes, the stress hormones remained elevated in the second DEX/CRH test, despite a reduction in depressive symptoms. Conclusions: This study provides evidence that, depending on gender and polymorphisms, there is continuous HPA axis overdrive in a proportion of patients irrespective of the status of depression. Considering the importance of stress hormones for cardiovascular disorders, our data might suggest that these patients are at high risk of comorbidity between depression and cardiovascular disorders. Copyright (c) 2008 S. Karger AG, Base

Clinical outcomes after implantation of a sutureless aortic bioprosthesis with concomitant mitral valve surgery: the SURE-AVR registry

Background: Early treatment of aortic valve stenosis is recommended in eligible symptomatic patients with severe aortic valve stenosis who would otherwise have a poor prognosis. The sutureless aortic valve bioprosthesis offers an alternative to standard aortic valve replacement with a sutured valve, but limited data are available in patients who have undergone multiple valve procedures involving the new, sutureless technology. We sought to investigate outcomes in high operative risk patients with previous or concomitant valve surgery who were implanted with a sutureless valve. Methods: SURE-AVR is an ongoing, prospective, multinational registry of patients undergoing aortic valve replacement. In-hospital and post-discharge outcomes up to 5 years were collected. Results: The study population comprised 78 patients (mean \ub1 SD: age 73.6 \ub1 7.6 years, logistic EuroSCORE 18.0 \ub1 17.5) enrolled at 13 sites who presented for concomitant or previous mitral valve repair (n\ua0= 45) or replacement (n\ua0= 33), with or without additional concomitant procedures, and were implanted with a sutureless valve. Mean \ub1 SD overall aortic cross-clamp time was 109 \ub1 41 min and cardiopulmonary bypass time was 152 \ub1 49 min. Mean \ub1 SD aortic pressure gradients decreased from 37.6 \ub1 17.7 mmHg preoperatively to 13.0 \ub1 5.7 mmHg at hospital discharge, and peak aortic pressure gradient from 61.5 \ub1 28.7 to 23.4 \ub1 10.6 mmHg. Early events included 1 death, 1 transient ischaemic attack, and 1 bleed (all 1.3%); a permanent pacemaker implantation was required in 6 patients (7.7%), and 2 reoperations (not valve related) (2.6%) took place. Over a median follow-up of 55.5 months (Q1 13.4, Q3 68.6), 12 patients died (6 cardiovascular and 6 non-cardiovascular, both 2.1% per patient-year). Five-year survival was 81.3%. Late paravalvular leak occurred in 2 patients (0.7% per patient-year) and permanent pacemaker implantation was required in 3 patients (0.1% per patient-year). There was no apparent rise in mean or peak aortic pressure gradient over the study. Conclusions: These results suggest that the sutureless implant is a technically feasible procedure during mitral surgery and is associated with good clinical outcomes

BISMICS consensus statement: implementing a safe minimally invasive mitral programme in the UK healthcare setting

Disseminating the practice of minimally invasive mitral surgery (mini-MVS) can be challenging, despite its original case reports a few decades ago. The penetration of this technology into clinical practice has been limited to centres of excellence and mitral surgery in most general cardiothoracic centres remains to be conducted via sternotomy access as a first line. The process for the uptake of mini-MVS requires clearer guidance and standardisation for the processes involved in its implementation. In this statement, a consensus agreement is outlined that describes the benefits of mini-MVS, including reduced post-operative bleeding, reduced wound infection, enhanced recovery and patient satisfaction. Technical considerations require specific attention and can introduced through simulation and/or use in conventional cases. Either endoballoon or aortic cross clamping are both recommended as well as femoral or central aortic cannulation, with the use of appropriate adjuncts and instruments. A coordinated team-based approach that encourages ownership of the programme by the team members is critical. A designated proctor is also recommended. The organisation of structured training and simulation, as well as planning the initial cases are important steps to consider. The importance of pre-empting complications and dealing with adverse events are described, including re-exploration, conversion to sternotomy, uni-lateral pulmonary oedema and phrenic nerve injury. Accounting for both institutional and team considerations can effectively facilitate the introduction of a mini-MVS service. This involves simulation, team-based training, visits to specialist centres and involvement of a designated proctor to oversee the initial cases

Sutureless Valve in Repeated Aortic Valve Replacement: Results from an International Prospective Registry

Objective: To report early and midterm results registry of patients undergoing repeated aortic valve replacement (RAVR) with sutureless prostheses from an international prospective registry (SURE-AVR). Methods: Between March 2011 and June 2019, 69 patients underwent RAVR with self-expandable sutureless aortic bioprostheses at 22 international cardiac centers.Results: Overall mortality was 2.9% with a predicted logistic EuroSCORE 11 of 10.7%. Indications for RAVR were structural valve dysfunction (84.1%) and infective prosthetic endocarditis (15.9%) and were performed in patients with previously implanted bioprostheses (79.7%), mechanical valves (15.9%), and transcatheter valves (4.3%). Minimally invasive approach was performed in 15.9% of patients. Rate of stroke was 1.4% and rate of early valve-related reintervention was 1.4%. Overall survival rate at 1 and 5 years was 97% and 91%, respectively. No major paravalvular leak occurred. Rate of pacemaker implantation was 5.8% and 0.9% per patient-year early and at follow-up, respectively. The mean transvalvular gradient at 1-year and 5-year follow-up was 10.5 mmHg and 11.5 mmHg with a median effective orifice area of 1.8 cm 2 and 1.8 cm 2 , respectively. Conclusions: RAVR with sutureless valves is a safe and effective approach and provides excellent clinical and hemodynamic results up to 5 years

Neuroactive steroids in depression and anxiety disorders: Clinical studies

Certain neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially 3 alpha-reduced pregnane steroids are potent positive allosteric modulators of the gamma-aminobutyric acid type A (GABA(A)) receptor. During major depression, there is a disequilibrium of 3 alpha-reduced neuroactive steroids, which is corrected by clinically effective pharmacological treatment. To investigate whether these alterations are a general principle of successful antidepressant treatment, we studied the impact of nonpharmacological treatment options on neuroactive steroid concentrations during major depression. Neither partial sleep deprivation, transcranial magnetic stimulation, nor electroconvulsive therapy affected neuroactive steroid levels irrespectively of the response to these treatments. These studies suggest that the changes in neuroactive steroid concentrations observed after antidepressant pharmacotherapy more likely reflect distinct pharmacological properties of antidepressants rather than the clinical response. In patients with panic disorder, changes in neuroactive steroid composition have been observed opposite to those seen in depression. However, during experimentally induced panic induction either with cholecystokinine-tetrapeptide or sodium lactate, there was a pronounced decline in the concentrations of 3 alpha-reduced neuroactive steroids in patients with panic disorder, which might result in a decreased GABAergic tone. In contrast, no changes in neuroactive steroid concentrations could be observed in healthy controls with the exception of 3 alpha,5 alpha-tetrahydrodeoxycorticosterone. The modulation of GABA(A) receptors by neuroactive steroids might contribute to the pathophysiology of depression and anxiety disorders and might offer new targets for the development of novel anxiolytic compounds. Copyright (c) 2006 S. Karger AG, Basel

The effects of delayed auditory and visual feedback on speech production

Monitoring the sensory consequences of articulatory movements supports speaking. For example, delaying auditory feedback of a speaker's voice disrupts speech production. Also, there is evidence that this disruption may be decreased by immediate visual feedback, i.e., seeing one's own articulatory movements. It is, however, unknown whether delayed visual feedback affects speech production in fluent speakers. Here, the effects of delayed auditory and visual feedback on speech fluency (i.e., speech rate and errors), vocal control (i.e., intensity and pitch), and speech rhythm were investigated. Participants received delayed (by 200 ms) or immediate auditory feedback, while repeating sentences. Moreover, they received either no visual feedback, immediate visual feedback, or delayed visual feedback (by 200, 400, and 600 ms). Delayed auditory feedback affected fluency, vocal control, and rhythm. Immediate visual feedback had no effect on any of the speech measures when it was combined with delayed auditory feedback. Delayed visual feedback did, however, affect speech fluency when it was combined with delayed auditory feedback. In sum, the findings show that delayed auditory feedback disrupts fluency, vocal control, and rhythm and that delayed visual feedback can strengthen the disruptive effect of delayed auditory feedback on fluency

Inflammatory myofibroblastic tumor of head of pancreas in a 5 Year-Old child

Inflammatory myofibroblastic tumor (IMT) is assumed as a rare benign tumor that can appear in various organs. Since Umiker et al. introduced inflammatory pseudotumors for the first time in 1954, it was found that occurrence in the head of pancreas is very rare (Baião et al., 2019) 1. Differentiating non-neoplastic lesions of pancreas from adenocarcinoma remains a challenge despite advances in diagnostic modalities whereas cystic and solid lesions and some normal anatomic variants can mimic malignancy (Okun and Lewin, 2016 Jan 1) 2. Histologic patterns of IMT can be identified as fibroblastic and myofibroblastic proliferation with inflammatory infiltrate. They are more common in Women and peak of occurrence is between 2 and 16 years of age (Mirshemirani et al., 2011) 3. In head of pancreas the disease can present with obstructive jaundice and the key for diagnosis is having a tissue specimen by means of needle biopsy. Though in all reported cases surgery is suggested as the lone treatment option, its natural history is obscure still and there can be a challenge in its treatment and also the extent of surgery. Here a new case of IMT of head of pancreas is reported. © 202

Major Depressive Disorder is Associated with Impaired Mitochondrial Function in Skin Fibroblasts

Mitochondrial malfunction is supposed to be involved in the etiology and pathology of major depressive disorder (MDD). Here, we aimed to identify and characterize the molecular pathomechanisms related to mitochondrial dysfunction in adult human skin fibroblasts, which were derived from MDD patients or non-depressive control subjects. We found that MDD fibroblasts showed significantly impaired mitochondrial functioning: basal and maximal respiration, spare respiratory capacity, non-mitochondrial respiration and adenosine triphosphate (ATP)-related oxygen consumption was lower. Moreover, MDD fibroblasts harbor lower ATP levels and showed hyperpolarized mitochondrial membrane potential. To investigate cellular resilience, we challenged both groups of fibroblasts with hormonal (dexamethasone) or metabolic (galactose) stress for one week, and found that both stressors increased oxygen consumption but lowered ATP content in MDD as well as in non-depressive control fibroblasts. Interestingly, the bioenergetic differences between fibroblasts from MDD or non-depressed subjects, which were observed under non-treated conditions, could not be detected after stress. Our findings support the hypothesis that altered mitochondrial function causes a bioenergetic imbalance, which is associated with the molecular pathophysiology of MDD. The observed alterations in the oxidative phosphorylation system (OXPHOS) and other mitochondria-related properties represent a basis for further investigations of pathophysiological mechanisms and might open new ways to gain insight into antidepressant signaling pathways