Choice of Vein‐Harvest Technique for Coronary Artery Bypass Grafting: Rationale and Design of the REGROUP Trial

The Randomized Endo‐vein Graft Prospective (REGROUP) trial ( ClinicalTrials.gov  NCT01850082) is a randomized, intent‐to‐treat, 2‐arm, parallel‐design, multicenter study funded by the Cooperative Studies Program (CSP No. 588) of the US Department of Veterans Affairs. Cardiac surgeons at 16 Veterans Affairs (VA) medical centers with technical expertise in performing both endoscopic vein harvesting (EVH) and open vein harvesting (OVH) were recruited as the REGROUP surgeon participants. Subjects requiring elective or urgent coronary artery bypass grafting using cardiopulmonary bypass with use of ≥1 saphenous vein graft will be screened for enrollment using pre‐established inclusion/exclusion criteria. Enrolled subjects (planned N = 1150) will be randomized to 1 of the 2 arms (EVH or OVH) after an experienced vein harvester has been assigned. The primary outcomes measure is the rate of major adverse cardiac events (MACE), including death, myocardial infarction, or revascularization. Subject assessments will be performed at multiple times, including at baseline, intraoperatively, postoperatively, and at discharge (or 30 days after surgery, if still hospitalized). Assessment of leg‐wound complications will be completed at 6 weeks after surgery. Telephone follow‐ups will occur at 3‐month intervals after surgery until the participating sites are decommissioned after the trial's completion (approximately 4.5 years after the full study startup). To assess long‐term outcomes, centralized follow‐up of MACE for 2 additional years will be centrally performed using VA and non‐VA clinical and administrative databases. The primary MACE outcome will be compared between the 2 arms, EVH and OVH, at the end of the trial duration.     

Taking a Better History for Behavioral Issues Pre‐ and Post‐Deep Brain Stimulation: Issues Missed by Standardized Scales

Objectives: To screen for potentially underreported behavioral changes in patients with idiopathic Parkinson's disease (PD) pre‐ and post‐deep brain stimulation (DBS), a retrospective data base review was performed. Methods: In total, 113 patients who underwent unilateral or bilateral DBS at the University of Florida in either subthalamic nucleus or globus pallidus internus for PD were screened for behavioral issues by asking about the presence or absence of seven neuropsychiatric symptoms (panic, fear, paranoia, anger, suicidal flashes, crying, and laughing). Results: There was a high prevalence of fear (16.3%), panic (14.0%), and anger (11.6%) at baseline in this cohort. In the first six months following DBS implantation, anger (32.6%), fear (26.7%), and uncontrollable crying (26.7%) were the most frequent symptoms reported. Those symptoms also were present following six months of DBS surgery (30.2%, 29.1%, and 19.8%, respectively). New uncontrollable crying occurred more in the acute postoperative stage (less than or equal to six months) (p= 0.033), while new anger occurred more in the chronic postoperative stage (greater than six months) (p= 0.017). The frequency of uncontrollable laughing significantly increased with bilateral DBS (p= 0.033). Conclusions: Many of the neuropsychiatric issues were identified at preoperative baseline and their overall occurrence was more than expected. There was a potential for worsening of these issues post‐DBS. There were subtle differences in time course, and in unilateral vs. bilateral implantations. Clinicians should be aware of these potential behavioral issues that may emerge following DBS therapy, and should consider including screening questions in preoperative and postoperative interviews. Standardized scales may miss the presence or absence of these clinically relevant issues.     

Coenzyme Q supports distinct developmental processes in Caenorhabditis elegans

Coenzyme Q (Q) regulates aging in Caenorhabditis elegans, and its deficiency leads to a variety of pathologies in humans. We used a coq-8 deleted strain to study the role of Q in C. elegans development and how it influences life span. Endogenous Q₉ content of coq-8(ok840) knockouts was demonstrated to be about 7% of that found in the wild-type, indicating the basal biosynthesis rate is reduced in this strain. Knockouts abnormally developed both gonads and hypodermis, showed reduced fertility and shortened life span, and this was partially recovered by ingestion of exogenous Q. Knockouts produced embryos that showed arrested development at the time of initial expression of coq-8 in embryo. Uridine, whose biosynthesis depends on mitochondrial Q, improved both egg production and progeny under Q-rich dietary conditions. COQ-8 is a candidate protein for post-translational regulation of Q biosynthesis rate and its expression correlates with Q content during the life cycle in C. elegans. We show for the first time that a critical level of Q is necessary to support embryo development and fertility in C. elegans. These results suggest that extra-mitochondrial function of Q is a key factor linking development and bioenergetics in C. elegans.     

The Effect of Body Mass Index on the Outcome of Critically Ill Surgical Patients

Background: The incidence of obesity is rising, and an increasing number of obese patients are admitted to surgical intensive care units (SICUs). However, it is not clear whether obesity is an independent risk factor for increased morbidity and mortality in SICU patients. We examined the effect of obesity on morbidity and mortality in patients admitted to the SICU in this study. Method: We reviewed prospectively acquired SICU data in normal and obese patients with an SICU length of stay >24 hours. Comparability of the groups was assessed using a χ² test or Fisher exact test, as appropriate, for categorical variables and analysis of variance (ANOVA) or the Kruskal‐Wallis test, as appropriate, for continuous variables. Results: Of the 1792 consecutive patients evaluated, 711 had a normal body mass index (BMI), and 993 were either preobese or obese. There was no statistically significant difference across the 5 BMI groups with respect to any of the 3 comorbidity indices (Acute Physiology and Chronic Health Evaluation III [APACHE III], Simplified Acute Physiology Score, or Multiple Organ Dysfunction Score). There was no statistically significant difference in the intensive care unit (ICU) length of stay and hospital length of stay or time‐to‐ICU mortality (log‐rank test P = .054) among the 5 BMI groups. A Cox regression analysis and backward elimination algorithm selected APACHE III to be the most important explanatory variable for survival time. Conclusion: Obesity does not affect the mortality of patients admitted to the SICU. We conclude that obesity cannot be used as an independent predictive mortality outcome variable in patients admitted to the SICU.     

Evaluation of the anticonvulsant and muscle relaxant effects of the methanol root bark extracts of Annona senegalensis

ObjectiveTo investigate the potentials of the root bark of Annona (A.) senegalensis in the control of seizure and related hypnotic and motor incoordination effects in mice using experimental models.MethodsThe methanol extract (ME) of the root bark of A. senegalensis was studied in mice using pentylenetetrazole (PTZ) induced convulsions, phenobarbitone induced sleeping time and motor coordination test on rota-rod performance. Acute toxicity and lethality (LD₅₀) test as well as phytochemical analysis were also carried out.ResultsThe extract (200, 400, 800 mg/kg) exhibited a non-dose dependent significant (P <0.05) delay in the onset of both tonic and clonic phases of seizure induced by PTZ (60 mg/kg, s.c.) as well as offered a 100% protection (200 mg/kg) in mice from PTZ induced seizures. The extract significantly (P <0.05) decreased the latency and increased the duration of phenobarbitone induced sleeping time. At 200 mg/kg, the extract exhibited a significant (P <0.05) motor incoordination. The acute toxicity test revealed an oral LD₅₀ of 1 296 mg/kg, while the phytochemical studies showed the presence of alkaloids, resins, glycosides, carbohydrate, reducing sugar, flavonoids, terpenoids, saponins and tannins.ConclusionThe extract of A. senegalensis possessed anticonvulsant activity with pronounced hypnotic and muscle relaxant effects.     

Intriguing issues of EGFR targeting in head and neck cancer

We have read the recent comprehensive review by Cruz et al.[1] regarding the targeting of receptor tyrosine kinases andtheir therapeutic perspectives in head and neck squamous cellcarcinomas (HNSCC). The major focus of this report was epidermalgrowth factor receptor (EGFR) biology and targeting. However,we feel     

Atrial natriuretic peptide in the diagnosis of patent ductus arteriosus

The aim of this study was to measure plasma atrial natriuretic peptide in preterm infants with a patent ductus arteriosus before and after closure with indomethacin. Atrial natriuretic peptide was measured in 28 preterm infants with clinical and echocardiographic evidence of a patent ductus arteriosus and in eight preterm infants who did not develop clinical evidence of a patent ductus arteriosus. Plasma concentration of atrial natriuretic peptide was measured by radioimmunoassay. In 18 infants the patent ductus arteriosus closed after one course of indomethacin; atrial natriuretic peptide levels decreased from median 1240 pg/ml (range 201-5483 pg/ml) to 266 pg/ml (range 62-1108 pg/ml). In four infants the patent ductus arteriosus closed after two courses of indomethacin and two infants had surgical ligation after indomethacin treatment failed. The patent ductus arteriosus closed spontaneously in four infants (atrial natriuretic peptide median level 152 pg/ml, range 61-495 pg/ml). In the eight infants without patent ductus arteriosus, atrial natriuretic peptide level was median 224 pg/ml (range 38-876 pg/ml). Measurement of plasma atrial natriuretic peptide concentration has a role in predicting when indomethacin treatment is indicated.