Citations

Introduction Lateral or posteriolateral coronary vein has been considered the optimal location of left ventricular (LV) lead placement for cardiac resynchronisation therapy (CRT). However, the long-term clinical outcomes of CRT based on LV lead location have not been sufficiently addressed. Methods Seven hundred and eighteen CRT-P/CRT-D recipients from Jan 2002 to Dec 2008 were studied. At the CRT implant, the LV lead placement was prioritised as posterolateral/lateral (PL, 50%), anterior lateral (AL, 31%), anterior interventricular (AI, 12%) or middle cardiac veins (MC, 7%). NYHA class and echocardiography were assessed before and after CRT. Clinical outcomes of CRT were compared among 4 LV lead locations. Results Patient baseline demographics, except the gender (P=0.03), were similar among four groups. After CRT, the improvement in NYHA class, LV ejection fraction (EF), and LV diastolic diameter were significantly improved comparably across four LV lead locations (table). The increase in LVEF by >5% were 46%, 47%, 41% and 42% in PL, AL, AI and MC groups (p=0.87). Conclusion The present study suggests that LV lead positioned in the alternative coronary veins, other than posteriolateral or lateral location, achieve comparable benefit in improvement of HF symptoms, and LV function after CRT. Table Comparison of clinic outcomes before and after CRT in different LV lead locations Lateral vein (N=359) Anterolateral vein (N=226) middle cardiac vein (N=49) anterior interventricular vein (N=84) Pre-CRT Post-CRT Pre-CRT Post-CRT Pre-CRT Post-CRT Pre-CRT Post-CRT NYHA 3.02±0.46 2.34±0.81* 2.92±0.53 2.34±0.89* 3.10±0.45 2.70±0.85* 2.98±0.52 2.43±0.86* LVEF (%) 23.57±7.28 30.82±11.67* 24.19±7.96 30.44±12.06* 24.97±7.62 30.72±11.43* 22.45±7.25 28.40±11.73* LVEDD (mm) 65.71±9.12 63.00±9.73* 65.79±8.87 63.88±9.88* 65.39±9.32 62.61±10.25* 68.48±8.92 64.86±9.67* LVESD (mm) 57.91±9.89 52.83±11.68* 56.69±10.23 53.03±12.01* 56.18±11.56 52.24±13.11* 59.09±10.04 55.32±13.30 RVD (mm) 0.90±0.86 0.82±0.85 0.85±0.92 0.82±0.85 0.86±0.83 1.01±0.84 0.56±0.77 0.78±0.91 RV dysfunction 1.05±0.92 0.88±0.92* 1.03±0.93 0.93±0.91 1.06±0.97 1.06±0.90 0.74±0.86 0.79±0.96 MR (m/s) 1.54±0.78 1.30±0.75* 1.57±0.83 1.35±0.75* 1.53±0.71 1.15±0.70* 1.36±0.69 1.19±0.68 * P<0.05 compared to pre-CRT.

Abstract BACKGROUND: Medically intractable epilepsy involving drop attacks can be difficult to manage and negatively affect quality of life. Most studies investigating the effect of corpus callosotomy (CC) on seizures have been limited, focusing on the pediatric population or drop seizures alone, with little attention to other factors influencing seizure outcome. OBJECTIVE: To assess seizure outcomes after CC in adults and children. METHODS: Retrospective analysis was performed on all patients who underwent CC (anterior two thirds, 1- or 2-stage complete) at our institution between 1990 and 2011. Change in frequency after CC was assessed for drop seizures and other seizure types. Multiple factors were evaluated for impact on seizure outcome. RESULTS: Fifty patients met inclusion criteria. The median age was 1.5 years at seizure onset and 17 years at time of surgery. Anterior two-thirds CC was performed in 28 patients, 1-stage complete in 17, and 2-stage complete in 5. All 3 groups experienced a significant decrease in drop seizures (P &lt; .001, P &lt; .001, and P = .020, respectively), with 40% experiencing complete resolution, and 64% dropping at least 1 frequency category. Other seizure types significantly decreased in anterior two-thirds CC and 1-stage complete (P = .0035, P = .001, respectively). Younger age at surgery correlated with better seizure outcomes (P = .043). CONCLUSION: CC for medically refractory generalizing epilepsy is effective for both drop seizures and other seizure types. CC should be considered soon after a patient has been deemed medically refractory because earlier age at surgery results in lower risk and better outcome.

The availability of population-based epidemiological data on the incident risk of stroke is very scarce in Argentina and other Latin American countries. In response to the priorities established by the World Health Organization and the United Nations, PREVISTA was envisaged as a population-based program to determine the risk of first-ever and recurrent stroke and transient ischemic attack incidence and mortality in Tandil, Buenos Aires, Argentina. The study will be conducted according to Standardized Tools for Stroke Surveillance (STEPS Stroke) methodology and will enroll all new (incident) and recurrent consecutive cases of stroke and transient ischemic attack in the City of Tandil between May 1st, 2013 and April 30, 2015. The study will include patients with ischemic stroke, non-traumatic primary intracerebral hemorrhage, subarachnoid hemorrhage, and transient ischemic attack. To ensure the inclusion of every cerebrovascular event during an observation period of two years, we will instrument an ‘intensive screening program’, consisting of a comprehensive daily tracking of every potential event of stroke or transient ischemic attack using multiple overlapping sources. Mortality would be determined during follow-up for every enrolled patient. Also, fatal community events would be screened daily through revision of death certificates at funeral homes and local offices of vital statistics. All causes of death will be adjudicated by an ad-hoc committee. The close population of Tandil is representative of a large proportion of Latin-American countries with low- and middle-income economies. The findings and conclusions of PREVISTA may provide data that could support future health policy decision-making in the region.

Background— Complex antithrombotic therapy (CAT) prescribed to elderly patients increases the risk of gastrointestinal bleeding. We quantified upper (UGIE) and lower gastrointestinal (LGIE) events, transfusions, and hospitalizations in a national cohort of elderly veterans prescribed CAT. Methods and Results— Veterans ≥60 years of age prescribed anticoagulant-antiplatelet, aspirin (ASA)-antiplatelet, ASA-anticoagulant, or triple therapy (ie, TRIP, anticoagulant-antiplatelet-ASA) were identified from the national pharmacy database (October 1, 2002 to September 30, 2008). Prescription-fill data were linked to Veteran Affairs and Medicare encounter files, each person-day of follow-up was assessed for CAT exposure, and outcomes were defined by using diagnostic code algorithms derived following chart abstraction. Incidence density ratios (compared with the reference category of no CAT) and survival analysis was conducted. Among 78 133 veterans (98.6% white; mean age, 72.3 [standard deviation 7.7]), 64% were prescribed ASA-antiplatelet and anticoagulant-antiplatelet and 6% were prescribed TRIP. The incidence of UGIE was 20.1/1000 patient-years, and the incidence of LGIE was 70.1/1000 patient-years. ASA-anticoagulant and TRIP were associated with the highest incidence of transfusion and hospitalization. A 40% to 60% increased risk of UGIE was observed with all strategies. LGIE was 30% higher with anticoagulant-antiplatelet, and transfusion increased with ASA-anticoagulant (hazard ratio, 6.1; 95% confidence interval, 5.2–7.1) and TRIP (hazard ratio, 5.0; 95% confidence interval, 4.2–5.8). Increased risk of hospitalization was noted with all strategies. The number needed to harm for UGIE or LGIE ranged from 52 to 65 and 15 to 23, respectively. The number needed to harm for hospitalization was 39 (anticoagulant-antiplatelet), 34 (ASA-anticoagulant), 67 (ASA-antiplatelet), and 45 (TRIP) patients. Conclusions— Among elderly patients, CAT-related LGIE and UGIE are clinically relevant risks resulting in increased hospitalizations and transfusions.

Abstract Purpose: Here, we describe a novel interplay between NAD synthesis and degradation involved in pancreatic tumor growth. Experimental Design: We used human pancreatic cancer cells, both in vitro (cell culture experiments) and in vivo (xenograft experiments), to demonstrate the role of NAD synthesis and degradation in tumor cell metabolism and growth. Results: We demonstrated that pharmacologic and genetic targeting of Nampt, the key enzyme in the NAD salvage synthesis pathway, inhibits cell growth and survival of pancreatic cancer cells. These changes were accompanied by a reduction of NAD levels, glycolytic flux, lactate production, mitochondrial function, and levels of ATP. The massive reduction in overall metabolic activity induced by Nampt inhibition was accompanied by a dramatic decrease in pancreatic tumor growth. The results of the mechanistic experiments showed that neither the NAD-dependent enzymes PARP-1 nor SIRT1 play a significant role on the effect of Nampt inhibition on pancreatic cancer cells. However, we identified a role for the NAD degradation pathway mediated by the NADase CD38 on the sensitivity to Nampt inhibition. The responsiveness to Nampt inhibition is modulated by the expression of CD38; low levels of this enzyme decrease the sensitivity to Nampt inhibition. In contrast, its overexpression decreased cell growth in vitro and in vivo, and further increased the sensitivity to Nampt inhibition. Conclusions: Our study demonstrates that NAD metabolism is essential for pancreatic cancer cell survival and proliferation and that targeting NAD synthesis via the Nampt pathway could lead to novel therapeutic treatments for pancreatic cancer. Clin Cancer Res; 20(1); 120–30. ©2013 AACR.

Background and Objectives. While excisional biopsy is recommended to diagnose cutaneous melanoma, various biopsy techniques are used in practice. We undertook this study to identify how frequently final tumor stage and treatment recommendations changed from diagnostic biopsy to final histopathology after wide local excision (WLE).Methods. We compared the histopathology of the dermatopathologist-reviewed diagnostic biopsy and final WLE in 332 cutaneous melanoma patients.Results. Tumor sites were extremity (51%), trunk (33%), and head/neck (16%). Initial biopsy types were excisional (56%), punch (21%), shave (18%), and incisional (5%). Most diagnostic biopsies were margin positive regardless of technique, and 36% of patients had residual melanoma on WLE. T-stage changed in 8% of patients, of whom 59% were diagnosed by punch biopsy, 15% by incisional biopsy, 15% by shave biopsy, and 11% by excisional biopsy (P<0.0001). Treatment recommendations changed in 6%: 2% after excisional biopsy, 5% after shave biopsy, 18% after punch biopsy, and 18% after incisional biopsy (P<0.0001).Conclusions. Although most biopsy margins were positive, T-stage and treatment changed for only a minority of melanoma patients. Our data provide valuable information to inform patient discussion regarding the likelihood of a change in prognosis and the need for secondary procedures after WLE. These data support the superiority of dermatopathologist-reviewed excisional biopsy when feasible.

Background and Purpose— Meta-analyses of extant genome-wide data illustrate the need to focus on subtypes of ischemic stroke for gene discovery. The National Institute of Neurological Disorders and Stroke SiGN (Stroke Genetics Network) contributes substantially to meta-analyses that focus on specific subtypes of stroke. Methods— The National Institute of Neurological Disorders and Stroke SiGN includes ischemic stroke cases from 24 genetic research centers: 13 from the United States and 11 from Europe. Investigators harmonize ischemic stroke phenotyping using the Web-based causative classification of stroke system, with data entered by trained and certified adjudicators at participating genetic research centers. Through the Center for Inherited Diseases Research, the Network plans to genotype 10 296 carefully phenotyped stroke cases using genome-wide single nucleotide polymorphism arrays and adds to these another 4253 previously genotyped cases, for a total of 14 549 cases. To maximize power for subtype analyses, the study allocates genotyping resources almost exclusively to cases. Publicly available studies provide most of the control genotypes. Center for Inherited Diseases Research–generated genotypes and corresponding phenotypes will be shared with the scientific community through the US National Center for Biotechnology Information database of Genotypes and Phenotypes, and brain MRI studies will be centrally archived. Conclusions— The Stroke Genetics Network, with its emphasis on careful and standardized phenotyping of ischemic stroke and stroke subtypes, provides an unprecedented opportunity to uncover genetic determinants of ischemic stroke.