Therapeutic benefits of distal ventricular pacing in mid-cavity obstructive hypertrophic cardiomyopathy.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) patients with left ventricular (LV) mid-cavity obstruction (LVMCO) often experience severe drug-refractory symptoms thought to be related to intraventricular obstruction. We tested whether ventricular pacing, guided by invasive haemodynamic assessment, reduced LVMCO and improved refractory symptoms. METHODS: Between December 2008 and December 2017, 16 HCM patients with severe refractory symptoms and LVMCO underwent device implantation with haemodynamic pacing study to assess the effect on invasively defined LVMCO gradients. The effect on the gradient of atrioventricular (AV) synchronous pacing from sites including right ventricular (RV) apex and middle cardiac vein (MCV) was retrospectively assessed. RESULTS: Invasive haemodynamic data were available in 14 of 16 patients. Mean pre-treatment intracavitary gradient was 77 ± 22 mmHg (in sinus rhythm) versus 21 ± 21 mmHg during pacing from optimal ventricular site (95% CI: -70.86 to -40.57, p < 0.0001). Optimal pacing site was distal MCV in 12/16 (86%), RV apex in 1/16 and via epicardial LV lead in 1/16. Pre-pacing Doppler-derived gradients were significantly higher than at follow-up (47 ± 15 versus 24 ± 16 mmHg, 95% CI: -37.19 to -13.73, p < 0.001). Median baseline NYHA class was 3, which had improved by ⩾1 NYHA class in 13 of 16 patients at 1-year post-procedure (p < 0.001). The mean follow-up duration was 4.6 ± 2.7 years with the following outcomes: 8/16 (50%) had continued symptomatic improvement, 4/16 had symptomatic decline and 4/16 died. Contributors to symptomatic decline included chronic atrial fibrillation (AF) (n = 5), phrenic nerve stimulation (n = 3) and ventricular ectopy (n = 1). CONCLUSION: In drug-refractory symptomatic LVMCO, distal ventricular pacing can reduce intracavitary obstruction and may provide long-term symptomatic relief in patients with limited treatment options. A haemodynamic pacing study is an effective strategy for identifying optimal pacing site and configuration

FCET2EC (From controlled experimental trial to = 2 everyday communication): How effective is intensive integrative therapy for stroke-induced chronic aphasia under routine clinical conditions? A study protocol for a randomized controlled trial

Background: Therapy guidelines recommend speech and language therapy (SLT) as the “gold standard” for aphasia treatment. Treatment intensity (i.e., ≥5 hours of SLT per week) is a key predictor of SLT outcome. The scientific evidence to support the efficacy of SLT is unsatisfactory to date given the lack of randomized controlled trials (RCT), particularly with respect to chronic aphasia (lasting for >6 months after initial stroke). This randomized waiting list-controlled multi-centre trial examines whether intensive integrative language therapy provided in routine in- and outpatient clinical settings is effective in improving everyday communication in chronic post-stroke aphasia. Methods/Design: Participants are men and women aged 18 to 70 years, at least 6 months post an ischemic or haemorrhagic stroke resulting in persisting language impairment (i.e., chronic aphasia); 220 patients will be screened for participation, with the goal of including at least 126 patients during the 26-month recruitment period. Basic language production and comprehension abilities need to be preserved (as assessed by the Aachen Aphasia Test).Therapy consists of language-systematic and communicative-pragmatic exercises for at least 2 hours/day and at least 10 hours/week, plus at least 1 hour self-administered training per day, for at least three weeks. Contents of therapy are adapted to patients’ individual impairment profiles.Prior to and immediately following the therapy/waiting period, patients’ individual language abilities are assessed via primary and secondary outcome measures. The primary (blinded) outcome measure is the A-scale (informational content, or 'understandability’, of the message) of the Amsterdam-Nijmegen Everyday Language Test (ANELT), a standardized measure of functional communication ability. Secondary (unblinded) outcome measures are language-systematic and communicative-pragmatic language screenings and questionnaires assessing life quality as viewed by the patient as well as a relative.The primary analysis tests for differences between the therapy group and an untreated (waiting list) control group with respect to pre- versus post 3-week-therapy (or waiting period, respectively) scores on the ANELT A-scale. Statistical between-group comparisons of primary and secondary outcome measures will be conducted in intention-to-treat analyses. Long-term stability of treatment effects will be assessed six months post intensive SLT (primary and secondary endpoints)

Extended lymph node resection versus standard resection for pancreatic and periampullary adenocarcinoma

BACKGROUND Pancreatic and periampullary adenocarcinomas account for some of the most aggressive malignancies, and the leading causes of cancer-related mortalities. Partial pancreaticoduodenectomy (PD) with negative resection margins is the only potentially curative therapy. The high prevalence of lymph node metastases has led to the hypothesis that wider excision with the removal of more lymphatic tissue could result in an improvement of survival, and higher rates of negative resection margins. OBJECTIVES To compare overall survival following standard (SLA) versus extended lymph lymphadenectomy (ELA) for pancreatic head and periampullary adenocarcinoma. We also compared secondary outcomes, such as morbidity, mortality, and tumour involvement of the resection margins between the two procedures. SEARCH METHODS We searched CENTRAL, MEDLINE, PubMed, and Embase from 1973 to September 2020; we applied no language restrictions. SELECTION CRITERIA Randomised controlled trials (RCT) comparing PD with SLA versus PD with ELA, including participants with pancreatic head and periampullary adenocarcinoma. DATA COLLECTION AND ANALYSIS Two review authors independently screened references and extracted data from study reports. We calculated pooled risk ratios (RR) for most binary outcomes except for postoperative mortality, for which we estimated a Peto odds ratio (Peto OR), and mean differences (MD) for continuous outcomes. We used a fixed-effect model in the absence of substantial heterogeneity (I² 25%). Two review authors independently assessed risk of bias, and we used GRADE to assess the quality of the evidence for important outcomes. MAIN RESULTS We included seven studies with 843 participants (421 ELA and 422 SLA). All seven studies included Kaplan-Meier curves for overall survival. There was little or no difference in survival between groups (log hazard ratio (log HR) 0.12, 95% confidence interval (CI) -3.06 to 3.31; P = 0.94; seven studies, 843 participants; very low-quality evidence). There was little or no difference in postoperative mortality between the groups (Peto odds ratio (OR) 1.20, 95% CI 0.51 to 2.80; seven studies, 843 participants; low-quality evidence). Operating time was probably longer for ELA (mean difference (MD) 50.13 minutes, 95% CI 19.19 to 81.06 minutes; five studies, 670 participants; moderate-quality evidence). There was substantial heterogeneity between the studies (I² = 88%; P < 0.00001). There may have been more blood loss during ELA (MD 137.43 mL, 95% CI 11.55 to 263.30 mL; two studies, 463 participants; very low-quality evidence). There was substantial heterogeneity between the studies (I² = 81%, P = 0.02). There may have been more lymph nodes retrieved during ELA (MD 11.09 nodes, 95% CI 7.16 to 15.02; five studies, 670 participants; moderate-quality evidence). There was substantial heterogeneity between the studies (I² = 81%, P < 0.00001). There was little or no difference in the incidence of positive resection margins between groups (RR 0.81, 95% CI 0.58 to 1.13; six studies, 783 participants; very low-quality evidence). AUTHORS' CONCLUSIONS There is no evidence of an impact on survival with extended versus standard lymph node resection. However, the operating time may have been longer and blood loss greater in the extended resection group. In conclusion, current evidence neither supports nor refutes the effect of extended lymph lymphadenectomy in people with adenocarcinoma of the head of the pancreas

Selective Intra-arterial Chemotherapy with Floxuridine as Second- or Third-Line Approach in Patients with Unresectable Colorectal Liver Metastases

Background: An outcome assessment was performed of patients with unresectable colorectal liver metastases (CRLM) treated in second or third line with floxuridine (FUDR)-based hepatic artery infusion (HAI). Methods: Twenty-three patients who were pretreated with systemic (immuno)chemotherapy received FUDR-HAI alone or combined with systemic chemotherapy. We reviewed patient charts and our prospective patient database for survival and associated risk factors. Results: Patients received FUDR-HAI for unresectable CRLM from January 2000 to September 2010. Twelve patients (52%) received concurrent systemic chemotherapy. Median overall survival (OS), progression-free survival (PFS), and hepatic PFS were 15.6months (range, 2.5-55.7months), 3.9months (range, 0.7-55.7months), and 5.5months (range, 1.6-55.7months), respectively. The liver resection rate after HAI was 35%. PFS was better in patients undergoing secondary resection than in patients without resection (hazard ratio [HR] 0.21; 95% confidence interval [95% CI] 0.07-0.66; P=0.0034), while OS showed a trend toward improvement (HR 0.4; 95% CI 0.13-1.2; P=0.09). No differences were observed in OS (P=0.69) or PFS (P=0.086) in patients who received FUDR-HAI alone compared with patients treated with combined regional and systemic chemotherapy. No statistically significant differences were seen in patients previously treated with one chemotherapy line compared with patients treated with two lines. Presence of extrahepatic disease was a negative risk factor for PFS (liver-only disease: HR 0.03; 95% CI 0.0032-0.28; P<0.0001). Toxicities were manageable with dose modifications and supportive measures. Conclusions: FUDR-HAI improves PFS and results in a trend toward improved OS in selected patients able to undergo liver resection after tumor is downsize

A Clinical Perspective on the Criteria for Liver Resection and the Use of Liver Function Tests

Ó The Author(s) 2009. This article is published with open access at Springerlink.com To the Editor, In a recently published survey of 100 liver centers, Breitenstein et al. [1] reported that on a global scale, (1) the average minimal remnant liver volume for resection is 25% (range = 15-40%) for normal liver parenchyma and 50% (range = 25–90%) for cirrhotic livers, (2) portal vein occlusion is employed in 89 % of the centers for purposes of augmenting liver volume before surgery, and that (3) 38 % of the centers employed liver function tests as part of their clinical routine, of which 76 % used the ICG clearance test. The interesting survey provoked a few issues that we feel obliged to address. The authors contend that ‘‘below a certain volume, a remnant liver cannot sustain metabolic, synthetic, and detoxifying functions’ ’ [1]—a statement that is unequivocal and uncontested. However, it should be born in mind that liver volume is not a directly proportional measure of liver function. We have demonstrated a few fundamental aspects of the volume-function relationship that support this notion: (i) Whereas liver function correlates with volume in uncompromised livers [2], there is significantly less correlation between liver volume an

Effects of stress beliefs on the emotional and biological response to acute psychosocial stress in healthy men

Background Negative beliefs about stress (e.g., “stress is bad”) constitute an independent risk factor for increased morbidity and mortality. One potential underlying mechanism are altered responses to acute psychosocial stress. The aim of this study was to investigate whether beliefs about stress are associated with physiological and endocrine stress response patterns. Methods A total of N = 77 healthy adults were randomised to an experimental and a placebo control group and were subsequently exposed to the Trier Social Stress Test (TSST). Stress beliefs were measured before and after a psychological manipulation aiming at fostering more balanced stress beliefs or a placebo manipulation. Self-reported stress was measured four times before/after the TSST, heart rate was assessed continuously, and cortisol was assessed eight times before/after the TSST. Results There was a significant decrease in negative stress beliefs (p < .001) and increase in positive stress beliefs (p < .001) in participants in the experimental condition, which was absent in participants in the placebo condition. The participants in the experimental group had more pronounced self-reported stress reactions (p = .028) while at the same time also showing more pronounced stress recoveries (p = .036). The findings regarding cortisol were mixed. Conclusions More balanced stress beliefs appeared to be associated with more efficient subjective responses to acute psychosocial stress. These findings attest to a potential mechanism translating negative stress beliefs into ill health while at the same time outlining targets for psychological interventions

Cosmesis and body image after single-port laparoscopic or conventional laparoscopic cholecystectomy: a multicenter double blinded randomised controlled trial (SPOCC-trial)

BACKGROUND: Emerging attempts have been made to reduce operative trauma and improve cosmetic results of laparoscopic cholecystectomy. There is a trend towards minimizing the number of incisions such as natural transluminal endoscopic surgery (NOTES) and single-port laparoscopic cholecystectomy (SPLC). Many retrospective case series propose excellent cosmesis and reduced pain in SPLC. As the latter has been confirmed in a randomized controlled trial, patient's satisfaction on cosmesis is still controversially debated. METHODS/DESIGN: The SPOCC trial is a prospective, multi-center, double blinded, randomized controlled study comparing SPLC with 4-port conventional laparoscopic cholecystectomy (4PLC) in elective surgery. The hypothesis and primary objective is that patients undergoing SPLC will have a better outcome in cosmesis and body image 12 weeks after surgery. This primary endpoint is assessed using a validated 8-item multiple choice type questionnaire on cosmesis and body image. The secondary endpoint has three entities: the quality of life 12 weeks after surgery assessed by the validated Short-Form-36 Health Survey questionnaire, postoperative pain assessed by a visual analogue scale and the use of analgesics. Operative time, surgeon's experience with SPLC and 4PLC, use of additional ports, conversion to 4PLC or open cholecystectomy, length of stay, costs, time of work as well as intra- and postoperative complications are further aspects of the secondary endpoint. Patients are randomly assigned either to SPLC or to 4PLC. Patients as well as treating physicians, nurses and assessors are blinded until the 7th postoperative day. Sample size calculation performed by estimating a difference of cosmesis of 20% (alpha = 0.05 and beta = 0.90, drop out rate of 10%) resulted in a number of 55 randomized patients per arm. DISCUSSION: The SPOCC-trial is a prospective, multi-center, double-blind, randomized controlled study to assess cosmesis and body image after SPLC

Las buenas maneras

Humans differ substantially in their ability to implicitly extract structural regularities from experience, as required for learning the grammar of a language. The mechanisms underlying this fundamental inter-individual difference, which may determine initial success in language learning, are incompletely understood. Here, we use diffusion tensor magnetic resonance imaging (DTI) to determine white matter integrity around Broca's area, which is crucially involved in both natural and artificial language processing. Twelve young, right-handed individuals completed an artificial grammar learning task, and DTI of their brains were acquired. Inter-individual variability in performance correlated with white matter integrity (increasing fractional anisotropy (FA)) in fibres arising from Broca's area (left BA 44/45), but not from its right-hemispheric homologue. Variability in performance based on superficial familiarity did not show this association. Moreover, when Broca's area was used as a seed mask for probabilistic tractography, we found that mean FA values within the generated tracts was higher in subjects with better grammar learning. Our findings provide the first evidence that integrity of white matter fibre tracts arising from Broca's area is intimately linked with the ability to extract grammatical rules. The relevance of these findings for acquisition of a natural language has to be established in future studies