NLM-Chem-BC7: manually annotated full-text resources for chemical entity annotation and indexing in biomedical articles.

The automatic recognition of chemical names and their corresponding database identifiers in biomedical text is an important first step for many downstream text-mining applications. The task is even more challenging when considering the identification of these entities in the article's full text and, furthermore, the identification of candidate substances for that article's metadata [Medical Subject Heading (MeSH) article indexing]. The National Library of Medicine (NLM)-Chem track at BioCreative VII aimed to foster the development of algorithms that can predict with high quality the chemical entities in the biomedical literature and further identify the chemical substances that are candidates for article indexing. As a result of this challenge, the NLM-Chem track produced two comprehensive, manually curated corpora annotated with chemical entities and indexed with chemical substances: the chemical identification corpus and the chemical indexing corpus. The NLM-Chem BioCreative VII (NLM-Chem-BC7) Chemical Identification corpus consists of 204 full-text PubMed Central (PMC) articles, fully annotated for chemical entities by 12 NLM indexers for both span (i.e. named entity recognition) and normalization (i.e. entity linking) using MeSH. This resource was used for the training and testing of the Chemical Identification task to evaluate the accuracy of algorithms in predicting chemicals mentioned in recently published full-text articles. The NLM-Chem-BC7 Chemical Indexing corpus consists of 1333 recently published PMC articles, equipped with chemical substance indexing by manual experts at the NLM. This resource was used for the evaluation of the Chemical Indexing task, which evaluated the accuracy of algorithms in predicting the chemicals that should be indexed, i.e. appear in the listing of MeSH terms for the document. This set was further enriched after the challenge in two ways: (i) 11 NLM indexers manually verified each of the candidate terms appearing in the prediction results of the challenge participants, but not in the MeSH indexing, and the chemical indexing terms appearing in the MeSH indexing list, but not in the prediction results, and (ii) the challenge organizers algorithmically merged the chemical entity annotations in the full text for all predicted chemical entities and used a statistical approach to keep those with the highest degree of confidence. As a result, the NLM-Chem-BC7 Chemical Indexing corpus is a gold-standard corpus for chemical indexing of journal articles and a silver-standard corpus for chemical entity identification in full-text journal articles. Together, these resources are currently the most comprehensive resources for chemical entity recognition, and we demonstrate improvements in the chemical entity recognition algorithms. We detail the characteristics of these novel resources and make them available for the community. Database URL: https://ftp.ncbi.nlm.nih.gov/pub/lu/NLM-Chem-BC7-corpus/.

NLM-Chem, a new resource for chemical entity recognition in PubMed full text literature.

Automatically identifying chemical and drug names in scientific publications advances information access for this important class of entities in a variety of biomedical disciplines by enabling improved retrieval and linkage to related concepts. While current methods for tagging chemical entities were developed for the article title and abstract, their performance in the full article text is substantially lower. However, the full text frequently contains more detailed chemical information, such as the properties of chemical compounds, their biological effects and interactions with diseases, genes and other chemicals. We therefore present the NLM-Chem corpus, a full-text resource to support the development and evaluation of automated chemical entity taggers. The NLM-Chem corpus consists of 150 full-text articles, doubly annotated by ten expert NLM indexers, with ~5000 unique chemical name annotations, mapped to ~2000 MeSH identifiers. We also describe a substantially improved chemical entity tagger, with automated annotations for all of PubMed and PMC freely accessible through the PubTator web-based interface and API. The NLM-Chem corpus is freely available.

Follow-up after asymptomatic penetrating thoracic injury: 3 hours is enough.

BACKGROUND: Patients with asymptomatic penetrating thoracic injuries routinely undergo chest radiographs (CXRs) upon emergency department (ED) arrival, and then 6 hours later to exclude delayed pneumothorax (PTX) or hemothorax (HTX). Although previous reports indicate that up to 12% (mean, 3%) of asymptomatic penetrating thoracic injuries are complicated by delayed PTX or HTX, we hypothesized that these events would be detectable after only 3 hours of observation. The purpose of this study was to compare the incidence of delayed thoracic injury at 3 hours and 6 hours using standard CXR. METHODS: A prospective trial of asymptomatic patients with penetrating thoracic injuries was conducted during 36 months. CXRs were performed upon arrival (supine, AP), and at 3 hours (upright, PA/lateral) and 6 hours (upright, PA/lateral). Patients with either injuries detected on initial CXR or cardiopulmonary symptoms were excluded. Findings from 3 hour and 6 hour CXRs were compared. Assuming a delayed PTX or HTX rate of 3%, the probability of detecting at least one delayed event between 3 hours and 6 hours in 100 patients is 95.25%. RESULTS: Of 648 patients with penetrating thoracic injuries, 100 patients both met inclusion criteria and completed the study. Patients were predominantly young (32.5 years +/- 13.3 years [mean +/- SD]) men (75% men) with stab wounds (75% stab wounds, 25% gunshot wounds). The mean length of stay for patients discharged from the ED was 8.8 hours +/- 2.6 hours. Although two patients developed a PTX between arrival and 3 hours, none developed after 3 hours. Patient charges, hospital costs, and radiation exposure were calculated for patients in our proposed study protocol, totaling $2802, $189, and 0.08 mSv, respectively. CONCLUSIONS: No patient in our study population developed a delayed PTX or HTX after 3 hours. Our results suggest that shortening the observation period after asymptomatic penetrating thoracic injuries to 3 hours is safe, cost-effective, minimizes radiation exposure, and may help relieve congested urban EDs.

Emergency department thoracotomy: still useful after abdominal exsanguination?

BACKGROUND: Although literature regarding emergency department thoracotomy (EDT) outcome after abdominal exsanguination is limited, numerous reports have documented poor EDT survival in patients with anatomic injuries other than cardiac wounds. As a result, many trauma surgeons consider prelaparotomy EDT futile for patients dying from intra-abdominal hemorrhage. Our primary study objective was to prove that prelaparotomy EDT is beneficial to patients with exsanguinating abdominal hemorrhage. METHODS: A retrospective review of 237 consecutive EDTs for penetrating injury (2000-2006) revealed 50 patients who underwent EDT for abdominal exsanguination. Age, gender, injury mechanism and location, field and emergency department (ED) signs of life, prehospital time, initial ED cardiac rhythm, vital signs, Glasgow Coma Score, blood transfusion requirements, predicted mortality, primary abdominal injuries, and the need for temporary abdominal closure were analyzed. The primary study endpoint was neurologically intact hospital survival. RESULTS: The 50 patients who underwent prelaparotomy EDT for abdominal exsanguination were largely young (mean, 27.3 +/- 8.2 years) males (94%) suffering firearm injuries (98%). Patients presented with field (84%) and ED signs of life (78%) after a mean prehospital time of 21.2 +/- 9.8 minutes. Initial ED cardiac rhythms were variable and Glasgow Coma Score was depressed (mean, 4.2 +/- 3.2). Eight (16%) patients survived hospitalization, neurologically intact. Of these eight, all were in hemorrhagic shock because of major abdominal vascular (75%) or severe liver injuries (25%) and all required massive blood transfusion (mean, 28.6 +/- 17.3 units) and extended intensive care unit length of stay (mean, 36.3 +/- 25.7 days). CONCLUSIONS: Despite critical injuries, 16% survived hospitalization, neurologically intact, after EDT for abdominal exsanguination. Our results suggest that prelaparotomy EDT provides survival benefit to penetrating trauma victims dying from intra-abdominal hemorrhage.

Emergency department thoracotomy: survival of the least expected.

Although emergency department thoracotomy (EDT) is often considered a controversial "last chance" method of resuscitation, we hypothesized that EDT performed in a busy urban Level I trauma center has significant salvage rates despite the absence of traditional survival predictors. A retrospective review revealed that 180 patients underwent EDT after traumatic arrest for penetrating injury between 2000 and 2005. All were deemed nonsalvageable by other resuscitation methods. Injury mechanism and location, signs of life (SOLs), initial cardiac rhythm, and presence of vital signs were analyzed. In total, 23 patients survived hospitalization neurologically intact. Compared to nonsurvivors, survivors more often suffered multiple stab wounds (21.7% vs. 1.9%, p = 0.001), presented with field (95.7% vs. 72.6%, p = 0.016) and ED (87.0% vs. 60.5%, p = 0.014) SOLs, had sustainable cardiac rhythms (sinus tachycardia, 43.5% vs. 10.2%, p = 0.001; normal sinus rhythm, 17.4% vs. 4.5%, p = 0.037), and had measurable vital signs (65.2% vs. 25.5%; p = 0.001). However, only 3 of 23 (13.0%) survivors had all survival predictors, and one survivor had none. Frequent predictors in survivors were field SOLs (95.7%), ED SOLs (87.0%), salvageable initial cardiac rhythms (78.3%), and obtainable vital signs (65.2%). Stabbing mechanism (30.4%) and cardiac injury location (30.4%) were least common. Had a strict policy of EDT performance based solely on the presence of survival predictors been followed and EDT withheld, several patients who ultimately survived would have died. Our study suggests that EDT is a technique that should be utilized for patients with critical penetrating injuries even in the absence of many traditional survival predictors.

A cost-effective approach to establishing a surgical skills laboratory.

BACKGROUND: Recent studies comparing inexpensive low-fidelity box trainers to expensive computer-based virtual reality systems demonstrate similar acquisition of surgical skills and transferability to the clinical setting. With new mandates emerging that all surgical residency programs have access to a surgical skills laboratory, we describe our cost-effective approach to teaching basic and advanced open and laparoscopic skills utilizing inexpensive bench models, box trainers, and animate models. METHODS: Open models (basic skills, bowel anastomosis, vascular anastomosis, trauma skills) and laparoscopic models (basic skills, cholecystectomy, Nissen fundoplication, suturing and knot tying, advanced in vivo skills) are constructed using a combination of materials found in our surgical research laboratories, retail stores, or donated by industry. Expired surgical materials are obtained from our hospital operating room and animal organs from food-processing plants. In vivo models are performed in an approved research facility. Operation, maintenance, and administration of the surgical skills laboratory are coordinated by a salaried manager, and instruction is the responsibility of all surgical faculty from our institution. RESULTS: Overall, the cost analyses of our initial startup costs and operational expenditures over a 3-year period revealed a progressive decrease in yearly cost per resident (2002-2003, $1,151; 2003-2004, $1,049; and 2004-2005, $982). CONCLUSIONS: Our approach to surgical skills education can serve as a template for any surgery program with limited financial resources.

Prehospital procedures before emergency department thoracotomy: "scoop and run" saves lives.

BACKGROUND: The role of prehospital healthcare personnel in the management of acutely injured patients is rapidly evolving. However, the performance of prehospital procedures on unstable, penetrating trauma patients remains controversial. The objective of this study is to test the hypothesis that survival of most critically injured penetrating trauma patients requiring emergency department thoracotomy (EDT) would be improved if procedures were restricted until arrival to the trauma bay. METHODS: A retrospective chart review on 180 consecutive penetrating trauma patients (2000-2005) who underwent EDT was performed. Patients were divided into two groups by mode of transportation and compared on the basis of demographics, clinical and physiologic parameters, prehospital procedures, and survival. RESULTS: Eighty-eight patients arrived by emergency medical services (EMS), and 92 were brought by police or private vehicle. Groups were similar with respect to demographics. Seven of 88 (8.0%) EMS-transported patients survived until hospital discharge, and 16 of 92 (17.4%) survived after police or private transportation. Overall, 137 prehospital procedures were performed in 78 of 88 (88.6%) EMS-transported patients, but no police- or private-transported patient underwent field procedures. Multivariate logistic regression analyses identified prehospital procedures as the sole independent predictor of mortality. For each procedure, patients were 2.63 times more likely to die before hospital discharge (OR = 0.38, 95% CI = 0.18-0.79, p = 0.0096). CONCLUSIONS: The performance of prehospital procedures in critical, penetrating trauma victims had a negative impact on survival after EDT in our study population. Paramedics should adhere to a minimal or "scoop and run" approach to prehospital transportation in this setting.

A ten-year retrospective review: does pyloric exclusion improve clinical outcome after penetrating duodenal and combined pancreaticoduodenal injuries?

OBJECTIVES: We sought to determine whether the performance of pyloric exclusion during repair of penetrating advanced duodenal injuries prevents postoperative duodenal fistulas and improves clinical outcome. METHODS: A retrospective chart review of patients from 1995 to 2004 with penetrating duodenal injuries >or=grade II and all combined pancreaticoduodenal injuries was performed. Patients managed either without or with pyloric exclusion were compared on the basis of age, sex, mechanism, injury grade, Injury Severity Score (ISS), hemodynamic stability, the presence of vascular injury or associated injuries, postoperative complications, length of hospital stay, and mortality. RESULTS: Fifteen of 29 patients were managed without pyloric exclusion and 14 with exclusion. Both groups were similar with respect to age, sex, mechanism, injury grade, ISS, hemodynamic stability, the presence of vascular injury, associated abdominal injuries, and mortality rates. A trend toward a higher overall complication rate (71% vs. 33%), pancreatic fistula rate (40% vs. 0%), and length of hospital stay (24.3 days vs. 13.5 days) was evident in the pyloric exclusion group. No duodenal fistula was detected in either patient group. CONCLUSION: In our study population, the performance of pyloric exclusion for penetrating advanced duodenal injury and combined pancreatic and duodenal injuries did not improve clinical outcome. The trend toward a greater overall complication rate, pancreatic fistula rate, and increased length of hospital stay in the pyloric exclusion group suggests that simple repair without pyloric exclusion is both adequate and safe for most penetrating duodenal injuries.

Immediate postoperative complications of combined penetrating rectal and bladder injuries.

BACKGROUND: Combined penetrating trauma involving the rectum and bladder has been associated with increased postoperative morbidity. Specific complications resulting from these injuries include colovesical fistula, urinoma, and abscess formation. METHODS: A retrospective review of Temple University Hospital trauma database was performed. Patients were categorized by having an isolated rectal (n = 29), isolated bladder (n = 16), or combined injury (n = 24). Records were reviewed for sex, age, site of injury, location of rectal and bladder injuries, operative intervention, fistula formation, urinoma formation, abscess formation, time to urinary catheter removal, length of intensive care unit stay, and length of hospital stay. RESULTS: Patient sex and age did not differ significantly between groups, nor was there a significant difference in location of rectal injury between groups. Presacral drainage was utilized in all patients with extraperitoneal injuries. Fecal diversion was performed in all patients, except two with intraperitoneal rectal injuries. Omental flap interposition between rectal and bladder injuries was utilized in one patient. No significant difference was noted in immediate postoperative complications between groups including fistula, urinoma, and abscess formation. However, all cases of colovesical fistula (n = 2) and urinoma (n = 2) formation were noted in those patients with rectal and posterior bladder injuries. CONCLUSIONS: Combined rectal and bladder injuries were not associated with an increase in immediate postoperative complications compared with isolated rectal and bladder injuries. However, postoperative fistula and urinoma formation occurred only in patients with a combined rectal and posterior bladder injury. Consequently, these patients may benefit from omental flap interposition between injuries to decrease fistula and urinoma formation.

WITHDRAWN BY THE AUTHORS: Molecular mechanism of extracellular nucleotide-induced degranulation from human polymorphonuclear leukocytes: Role of leukotriene B4 and p38 MAP kinase as essential intermediates.

WITHDRAWN BY THE AUTHORS.

Effects of aldosterone receptor blockade in patients with mild-moderate heart failure taking a beta-blocker.

AIMS: Spironolactone improves prognosis in severe heart failure (HF). We investigated its effects in patients with mild-moderate HF treated with an ACE inhibitor and beta-blocker. METHODS AND RESULTS: Randomised, double-blind, parallel-group, 3-month comparison of placebo and spironolactone (25 mg daily) in 40 patients in New York Heart Association (NYHA) class I (20%), II (70%) or III (10%), with a left ventricular ejection fraction of <40%. The mean (standard error) changes from baseline in the spironolactone and placebo groups were, respectively: i) B-type natriuretic peptide (BNP) -53.4(22.2) pg/mL and +3.3(12.1) pg/mL, P=0.04, ii) pro-collagen type III N-terminal amino peptide (PIIINP) -0.6(0.2) micromol/L and +0.02(0.2) micromol/L, P=0.02 and iii) creatinine +10.7(3.2) micromol/L and -0.3(2.6) micromol/L, P=0.01. Compared with placebo, spironolactone therapy was associated with a reduction in self-reported health-related quality of life: change in visual analog score: -6 (3) vs. +6 (4); P=0.01. No differences were observed on other biochemical, neurohumoral, exercise and autonomic function assessments. CONCLUSION: In patients with mild-moderate HF, spironolactone reduced neurohumoral activation (BNP) and a marker of collagen turnover (PIIINP) but impaired renal function and quality of life. The benefit-risk ratio of aldosterone blockade in mild HF is uncertain and requires clarification in a large randomised trial.

Gastrostomy tube placement outcomes: comparison of surgical, endoscopic, and laparoscopic methods.

BACKGROUND: Advances in percutaneous endoscopic gastrostomy (PEG) and laparoscopic (LAP) techniques now allow for less invasive placement of gastrostomy tubes. This study compared morbidities and feeding outcomes of these procedures with standard surgical (OPEN) insertion. METHODS: Gastrostomy tubes placed in the operating room by the PEG, LAP, and OPEN methods were compared for insertion times, tube insertion and maintenance complications, enteral feeding complications, and feeding start days. Patients with concomitant intra-abdominal procedures were excluded. Patients were followed for 6 days after tube placement. RESULTS: A total of 91 catheters (PEG = 23, LAP = 39, OPEN = 29) were inserted in the operating room for indications of ventilator-dependent respiratory failure (45), dysphagia (30), head and neck cancer (9), and decreased mental status (7). No patients were fed on the day of the procedure. Insertion times were significantly longer (p < .05) in the OPEN technique (68 minutes) vs LAP (48 minutes) and PEG (30 minutes). Insertion complications occurred in the LAP and PEG cohorts (3 failed LAP, 1 failed PEG), and maintenance complications were higher in the LAP group, including 1 episode each of cellulitis, bleeding, and serous drainage. Twenty enteral feeding complications in 17 patients occurred in all groups (9 in LAP vs 6 in PEG and 5 in OPEN), and included emesis (6), high residual (5), diarrhea (3), ileus (3), nausea (2), and pain after feeding (1). Overall complications were significantly lower in the PEG (7) and OPEN (5) groups compared with the LAP group (15). Feeding start day was significantly delayed in the OPEN technique (2.1 days vs 1.7 in PEG and 1.5 in LAP); however, no difference was found in days to goal among groups (4.4-4.8 days). CONCLUSIONS: PEG should be the procedure of choice for placement of gastrostomy tubes. If PEG is contraindicated, then OPEN technique may be best due to fewer complications, although insertion time is longer than the LAP technique.

Successful collaborative model for trauma skills training of surgical and emergency medicine residents in a laboratory setting.

OBJECTIVES: To determine whether interdepartmental educational and technical resources could be combined to successfully train surgery and emergency medicine residents in common diagnostic and therapeutic trauma skills outside the traditional hospital setting. DESIGN: Curriculum improvement survey. SETTING: Surgical Skills Laboratory, Temple University School of Medicine, Philadelphia, Pennsylvania. PARTICIPANTS: A total of 35 surgery residents (PGY 1 to 5) and 26 emergency medicine residents (PGY 1 to 3). METHODS: Emergency medicine attendings used human volunteers to train surgery residents in Focused Assessment with Sonography in Trauma (FAST). Trauma surgery attendings used a porcine model to teach emergency medicine residents tracheostomy, peripheral venous cutdown, diagnostic peritoneal lavage, tube thoracostomy, and bilateral thoracotomy. Upon completion of the courses, all residents were surveyed using a 5-point Likert scale to assess this teaching model. RESULTS: The percentage of residents reporting an improvement in knowledge levels after the course increased significantly (p < 0.003) for all skill modules (FAST, 14% vs 73%; tracheostomy, 20% vs 64%; peripheral venous cutdown, 25% vs 71%; diagnostic peritoneal lavage, 16% vs 60%; tube thoracostomy, 42% vs 92%; thoracotomy, 15% vs 42%). A significant (p < 0.05) increase in comfort levels during performance of the procedures in the clinical setting was also anticipated for all skills modules (FAST, 11% vs 60%; tracheostomy, 12% vs 50%; peripheral venous cutdown, 15% vs 31%; diagnostic peritoneal lavage, 12% vs 58%; tube thoracostomy, 35% vs 73%; thoracotomy, 0% vs 15%). PGY 1 to 4 surgery residents and PGY 1 and 2 emergency medicine residents perceived the greatest benefit (p < 0.05) from their respective courses. The overwhelming majority (89% to 100%) of surgery and emergency medicine residents felt the course was valuable and transferable to the clinical trauma setting. CONCLUSIONS: Interdepartmental collaboration between the Department of Surgery and Department of Emergency Medicine offered a unique training relationship that was a positive educational experience for all residents.

Potential suitability for transplantation of hearts from human non-heart-beating donors: data review from the Gift of Life Donor Program.

BACKGROUND: Organ availability limits use of heart transplantation for treatment for end-stage heart disease. Hearts are currently obtained from donors declared brain dead (heart-beating donors [HBDs]). Although use of hearts from non-heart-beating donors (NHBDs) could reduce the shortage, they are considered unusable because of possible peri-mortem ischemic injury. METHODS: To project how use of NHBD hearts could increase heart donation, we retrospectively reviewed donor databases from the Gift of Life Donor Program (GLDP), our local organ procurement organization, from 2001 through 2003. We screened the NHBD population using conservative donor criteria, assuming an acceptable hypoxic/ischemic time (time from withdrawal of care to cross-clamp) of 30 minutes. RESULTS: During the study period, there were 894 HBDs, 334 heart transplants and 119 NHBDs. NHBDs were similar to HBDs with respect to gender and ethnicity, but NHBDs were proportionately younger. Of 119 NHBDs, 55 did not meet the age criteria (< or =45 years) and 20 were eliminated because of incomplete data. Eighty-two NHBDs were cross-clamped within 30 minutes of care withdrawal. Twenty NHBDs met all cardiac donor criteria, and 14 of these 20 had hypoxic/ischemic times < or =30 minutes. Pro rata estimation for the 20 NHBDs with incomplete data suggested 7 potential additional donors. CONCLUSIONS: Based on our assumptions, 12% to 18% of NHBDs in the study period (14 to 21 of 119 total) were potential heart donors, representing a 4% to 6% increase over of the number of heart transplants performed during the same time interval.

Effects of nutrient and hemoglobin enriched cell free perfusates upon ex vivo isolated rat heart preparation.

We evaluated the effects of nutrient enriched medium and hemoglobin based oxygen carrier (HBOC) upon myocardial functional recovery after 15 minutes of warm ischemia in an isovolumic Langendorff rat heart model. Hearts (n = 8/group) were perfused at constant pressure (90 mm Hg) with Krebs-Henseleit buffer or HEPES modified cell culture medium (M199) in the absence and presence of HBOC. Hearts received 15 minutes of normothermic no flow ischemia followed by 60 minutes reperfusion. Hemodynamics, coronary flow, and tissue water content were measured, and microscopic evidence of injury including TUNEL assay was assessed. Preischemic left ventricular performance (left ventricular developed pressure and maximum rate of positive and negative change in systolic pressure) and coronary flow were similar among groups. At 60 minutes of reperfusion, M199 alone provided more stable and complete left ventricular systolic and diastolic functional recovery than any other perfusate. Coronary flow rates reflected left ventricular function observed under each perfusate condition. TUNEL assay showed arterial endothelial cell death in some hearts perfused with HBOC. Tissue water content did not reflect functional recovery. The combination of M199 and HBOC was associated with poor recovery and elevated perfusate methemoglobin. In this system, postischemic dysfunction is prevented by components in M199. Added HBOC does not improve functional recovery and negates the salutary effects of M199, possibly by augmenting methemoglobin formation.

Successful transplantation of an older donor heart with documented myocardial bridging: a case report.

Myocardial bridging, the overlying of myocardial tissue onto epicardial coronary arteries, is an anatomic variant that is widely present in the general population. This condition can be associated with reduced forward coronary flow. Once these hearts are identified in potential donors by either visual inspection or coronary catheterization, they may no longer be considered suitable for transplantation. We present a case study that successfully utilized such a heart explanted from an older donor with "bench" myotomy repair before implantation.

Effect of adenoviral-mediated transfer of transforming growth factor-beta1 on colonic anastomotic healing.

PURPOSE: Transforming growth factor-beta1 plays a central role in colonic repair. We examined the temporal effect of vector-mediated transfer of transforming growth factor-beta1 on colonic anastomotic healing. METHODS: Male Sprague-Dawley rats (n = 24) underwent transection of the distal colon and single-layer anastomosis. Proximal to the anastomosis, the colon was again transected and a colostomy was matured proximally. The distal colon was intubated with a silicone catheter, tunneled along subcutaneous tissues, and connected to a swivel apparatus for postoperative luminal infusion. Rats were randomized into four groups (n = 6 each). Two control groups received 10(10) plaque-forming units of a Type 5 E1-deleted adenovirus carrying the bacterial beta-galactosidase gene either immediately following surgery or on postoperative Day 3. The treatment groups received transforming growth factor-beta1 with the same viral construct at parallel time points. On postoperative Day 6, anastomotic bursting pressure and site were determined in situ with the anastomotic tissue subsequently harvested and analyzed by enzyme-linked immunosorbent assay for beta-galactosidase and transforming growth factor-beta1. RESULTS: When compared with its corresponding control, the group that received the transforming growth factor-beta1 gene on postoperative day 3 had a significantly higher bursting pressure (mmHg; 119 +/- 16 vs. 160 +/- 12, mean +/- SD; P = 0.001). While the majority of colons (5/6) from the control group burst at the anastomosis, none of the colons in the group that received transforming growth factor-beta1 on day 3 burst at the anastomotic site (P = 0.007). Beta-Galactosidase levels (pg/ml) in anastomotic tissue were significantly increased in both control groups when compared with their respective treatment groups (101 +/- 43 vs. 38 +/- 30, P = 0.01 when infused the day of surgery and 243 +/- 92 vs. 50 +/- 30, P = 0.009 when infused on day 3). Anastomotic levels of transforming growth factor-beta1 were also increased in the group receiving the transforming growth factor-beta1 gene on day 3 (214 +/- 66 vs. 135 +/- 24, P = 0.02). CONCLUSIONS: Gene transfer into the healing colonic anastomosis can be effectively achieved via intraluminal administration of adenoviral vectors. Transfer of transforming growth factor-beta1 increased the strength of colonic anastomoses when given at Day 3 but not at Day 0, demonstrating its diverse effects in the wound healing sequence. Thus, gene transfer of transforming growth factor-beta1 may avoid the need for a diverting stoma in cases of rectal surgery and impaired healing resulting from chemotherapy or radiation.

Effect of older donor age on risk for mortality after heart transplantation.

BACKGROUND: Despite the increasingly common use of donor hearts at least 50 years of age, controversy still remains regarding long-term outcome. Our goal was to determine if older donor age is associated with an increased risk of mortality and specifically if the use of donor hearts at least 50 years of age reduces survival. METHODS: We retrospectively studied records of all primary heart transplants performed between January 1990 and July 2002. Fifty-six patients who had received donor hearts at least 50 years of age were compared with 611 recipients of donor hearts less than 50 years of age. Clinicopathologic parameters were analyzed for their effect on mortality using the Cox proportional hazard model with calculation of hazard ratios (HR). Cut-point analysis of donor age was used to determine which donor age is associated with the greatest risk of mortality after transplant. RESULTS: Recipients of donor hearts at least 50 years of age were older (58.5 years +/- 7.0 vs 53.2 +/- 11.6; mean +/- standard deviation [SD]; p < 0.0001), suffered more often from ischemic cardiomyopathy (69% vs 50%, p = 0.01), and experienced a longer waiting time (192.2 days +/- 301.0 vs 138.6 +/- 190.8, p < 0.0001). Donor hearts at least 50 years of age (age 54.1 +/- 3.5 years) were more often female (50% vs 34%, p = 0.03), died less often of "head trauma" (9% vs 42%, p < 0.0001), and exhibited fewer cytomegalovirus (CMV) mismatches (29% vs 39%, p = 0.04) than donor hearts less than 50 years of age (age 26.8 +/- 12.3 years). Multivariate predictors of mortality were rejection index (HR 1.90 per unit [rejections/100 survival days], p < 0.0001), donor age (HR 1.16 per 10-year increment, p = 0.002), and recipient age (HR 1.24 per 10-year increment, p = 0.04). Recipients of donor hearts at least 50 years of age had reduced 1-year and 5-year survival ([65.7% vs 81.7%, p < 0.05] and [48.3% vs 68.4%, p < 0.05], respectively), as well as a higher proportion of deaths occurring within 1 month of transplant (41% of total deaths vs 23%, p = 0.06). Cut-point analysis indicated the characteristic of donor age of at least 40 years (categorical variable) to predict mortality with the same degree of fit as age used as a continuous variable. CONCLUSIONS: Although we observed a substantial reduction in survival among patients who were allocated donor hearts at least 50 years of age, this difference was not solely attributable to the categorical variable of donor age 50 in this group. Donor age as a continuous variable, however, was determined to be a notable predictor of survival and use of the donor age cut-point of 40 years (categorical variable) allowed risk stratification with similar accuracy. The use of a donor age cut-point of 40 years may be a useful clinical criterion for graft-related risk assessment.