Neuromodulation in Psychiatric disorders: Experimental and Clinical evidence for reward and motivation network Deep Brain Stimulation: Focus on the medial forebrain bundle

Deep brain stimulation (DBS) in psychiatric illnesses has been clinically tested over the past 20 years. The clinical application of DBS to the superolateral branch of the medial forebrain bundle in treatment‐resistant depressed patients—one of several targets under investigation—has shown to be promising in a number of uncontrolled open label trials. However, there are remain numerous questions that need to be investigated to understand and optimize the clinical use of DBS in depression, including, for example, the relationship between the symptoms, the biological substrates/projections and the stimulation itself. In the context of precision and customized medicine, the current paper focuses on clinical and experimental research of medial forebrain bundle DBS in depression or in animal models of depression, demonstrating how clinical and scientific progress can work in tandem to test the therapeutic value and investigate the mechanisms of this experimental treatment. As one of the hypotheses is that depression engenders changes in the reward and motivational networks, the review looks at how stimulation of the medial forebrain bundle impacts the dopaminergic system.     

Association Between Patient and Physician Sex and Physician-Estimated Stroke and Bleeding Risks in Atrial Fibrillation

Background

Physicians treating nonvalvular atrial fibrillation (AF) assess stroke and bleeding risks when deciding on anticoagulation. The agreement between empirical and physician-estimated risks is unclear. Furthermore, the association between patient and physician sex and anticoagulation decision-making is uncertain.

Erythropoietin deficiency and relative resistance cause anaemia in post-renal transplant recipients with normal renal function

BACKGROUND: Following successful renal transplantation, blood erythropoietin(Epo) levels peak in two phases during the first 2–3 months,and blood haemoglobin/haematocrit (Hb/Hct) levels are restoredto normal in a period of 2–6 months. However, some transplantrecipients continue to remain anaemic in spite of normal graftfunction and in the absence of recognizable causes. The roleof endogenous Epo production in the causation of anaemia insuch patients is poorly understood and has been investigatedin this study. METHODS: Twenty-three post-renal transplant recipients with stable normalrenal function were studied. Eleven of these patients had normalHb/Hct levels (group 1) and served as control for the rest 12patients with anaemia (group 2). Patients included in group2 had no readily recognizable cause for their anaemia. Otherlaboratory and clinical findings were similar in both groups.Patients with erythrocytosis were excluded. Serum Epo levelswere measured in all patients. Five patients in group 2 weretreated with recombinant human erythropoietin (rHuEpo) and theirerythropoietic response was assessed. rHuEpo was discontinuedwhen the target Hb/Hct levels (lowest normal range) were achievedand the patients were followed up for a further period of 9–12months. RESULTS: Five patients in group 1 had normal expected serum Epo levelswhereas the other six patients had inappropriately high serumEpo levels with respect to their Hb/Hct status suggestive ofrelative ‘Epo resistance’. Serum Epo levels in allpatients except two in group 2 were low indicative of ‘Epodeficiency’. The two exceptional patients in group 2 hadhigher serum Epo levels in the presence of anaemia suggestiveof relative ‘Epo resistance’. All five patients treated with rHuEpo responded adequately byachieving normal Hb/Hct levels. Three of them were originally‘Epo deficient’ and they reached target Hb/Hct levelsin a mean period of 4 weeks, requiring a mean cumulative rHuEpodose of 428.3 units/kg. The other two patients with higher initialserum Epo levels, and considered to be ‘Epo resistant’,required an average of 11 weeks of treatment and a mean cumulativerHuEpo dose of 1582.5 units/ kg, indicating an increased Epodemand. On cessation of therapy the Hb/Hct levels fell in allfive patients to pretreatment values in 6 months. CONCLUSIONS: There are important variations in the endogenous Epo productionin renal transplant patients with normal renal function, thecause of which is not clear. Epo deficiency and relative Eporesistance play a causative role for anaemia in some post-renaltransplant recipients with stable normal renal function. Theyrespond adequately to rHuEpo administration.     

Extended trans-septal approach for mitral valve surgery: Our early experience

Background Extended trans septal (ETS) approach for mitral valve surgery often divides the artery to the Sino-Atrial node. The clinical implication of this is contentious. We analyzed our early results with ETS approach. Methods Between June 1998 and September 2003 eleven patients underwent mitral valve surgery by ETS approach. Six were females. Age ranged from 19 years to 67 years (median 40 years). Six underwent mitral valve replacement (MVR). Four underwent aortic and mitral (double) valve replacement (DVR). One had mitral valve repair. Three had additional procedures (tricuspid valve repair=1, Coronary artery bypass=1, Aorto bifemoral graft=1). Cardiopulmonary bypass ranged from 64 minutes to 77 minutes (median 72 minutes) for MVR and 112 minutes to 178 minutes (median 140 minutes) for DVR. Aortic cross clamp times ranged from 39 minutes to 52 minutes (median 47 minutes) for MVR and 74 minutes to 120 minutes (median 95 minutes) for DVR. Results There was no mortality or morbidity attributed to the ETS approach. One early death in emergency DVR was due to heart failure. Three patients needed seqeuntial pacing in the immediate post-operative period. Nine out of ten survivors were back to their preoperative rhythms on hospital discharge (6 sinus rhythm; 3 atrial fibrillation). One patient with preoperative trifascicular block who underwent reoperation to fix a paravalvular mitral leak needed a permanent pacemaker (VVI). The follow-up ranged from 1 month to 64 months (median 6 months) and is 100% complete. There was no late death or new arrhythmia. Conclusions Extended trans septal approach is safe. It gives excellent exposure of the mitral valve. division of the sinus node artery is not deleterious in the short to intermediate term. Presented at the 50th Annual Meeting of IACTS. New Delhi, Feb. 2004.     

The index manic episode in juvenile-onset bipolar disorder: the pattern of recovery.

OBJECTIVE: Recent studies of patients with juvenile bipolar disorder report low rates of recovery and high rates of chronicity. However, we lack data on the short-term outcome. This study examines the pattern of recovery from the index episode in an aggressively treated juvenile sample. METHOD: We assessed 25 subjects (< 16 years) with a diagnosis of mania, using the Diagnostic Interview for Children and Adolescents-Revised) (DICA-R), Young Mania Rating Scale (YMRS), and Children's Global Assessment Scale (CGAS) at intake and at 3 and 6 months. We studied the time taken to recover from the index episode, the level of functioning, and the factors predicting them. RESULTS: After 6 months, 24 (96%) subjects had recovered from the index manic episode. The median time to recovery was 27 days. Total episode length was significantly longer among those with previous affective episodes. CONCLUSIONS: The findings suggest that juvenile-onset mania has high rates of recovery and low rates of chronicity. These differences from the existing literature need further exploration.     

Bariatric surgery improves cardiac function in morbidly obese patients with severe cardiomyopathy.

BACKGROUND: Longstanding morbid obesity can be associated with severe cardiomyopathy. However, the safety and efficacy of bariatric surgery in patients with severe cardiomyopathy has not been studied, and the effect of surgical weight loss on postoperative cardiac function is also unknown. In addition, morbidly obese patients have significantly increased mortality associated with cardiac transplantation, often precluding them from becoming recipients. METHODS: A retrospective study of patients with a left ventricular ejection fraction < or =35% who underwent bariatric surgery (1998-2005) was performed. Short-term morbidity/mortality, length of stay, excess weight loss, pre- and postoperative left ventricular ejection fraction, and New York Heart Association (NYHA) functional class were assessed. RESULTS: A total of 14 patients (10 men and 4 women) with a mean preoperative body mass index of 50.8 +/- 2.04 kg/m(2) underwent bariatric surgery (10 underwent laparoscopic Roux-en-Y gastric bypass, 1 open Roux-en-Y gastric bypass, 2 sleeve gastrectomy, and 1 laparoscopic gastric banding). The complications were pulmonary edema in 1, hypotension in 1, and transient renal insufficiency in 2. The median length of stay was 3.0 days (range 2-9). The mean excess weight loss at 6 months was 50.4%, with a decrease in the mean body mass index from 50.8 +/- 2.04 kg/m(2) to 36.8 +/- 1.72 kg/m(2). The mean left ventricular ejection fraction at 6 months had significantly improved from 23% +/- 2% to 32% +/- 4% (P = .04), correlating with improved functional capacity, as measured by the NYHA classification. Preoperatively, 2 patients (14%) had an NYHA classification of IV, 6 (43%) a classification of III, and 6 (43%) a classification of II. At 6 months postoperatively, no patient had an NYHA classification of IV, 2 (14%) had a classification of III, and 12 (86%) an NYHA classification of II. Two patients had undergone cardiac transplant evaluations preoperatively and underwent successful transplantation after weight loss. CONCLUSION: The results of our study have shown that bariatric surgery for patients with cardiomyopathy is feasible and effective. Surgically induced weight loss results in both subjective and objective improvement in cardiac function. In addition, surgical weight loss can provide a bridge to transplantation in patients who were prohibited secondary to their morbid obesity.