The Association between Frailty and Short-Term Outcomes in an Intensive Care Unit Rehabilitation Trial: An Exploratory Analysis.

BACKGROUND: Physical therapy initiated early in an ICU stay may reduce functional deficits in critically ill patients; however, the association of frailty with outcomes in those receiving early in-ICU rehabilitation is unknown. OBJECTIVE: To estimate the association between frailty and 3 outcomes in patients enrolled in an ICU randomized clinical trial (RCT). DESIGN: Exploratory secondary analyses of the CYCLE pilot RCT (NCT02377830). SETTING: 7 Canadian ICUs. PARTICIPANTS: Previously ambulatory critically ill adults. INTERVENTION: Participants were randomized to early in-bed cycling plus routine physiotherapy versus early routine physiotherapy alone. MEASUREMENTS: Using regression analyses, we modelled the association between pre-hospital Clinical Frailty Scale (CFS) scores, Physical Function in ICU Test-scored (PFIT-s), muscle strength, and mortality at hospital discharge, adjusting for illness severity (APACHE II) and the randomized intervention. We explored the influence of imputing mean PFIT-s and strength scores for decedents, and with listwise deletion of decedents in a sensitivity analysis. RESULTS: Of 66 patients, 2 had missing data, 2 had incomplete data, and 21 died by hospital discharge. At hospital discharge for 66 patients, frailty was not associated with PFIT-s (mean difference (MD) [95% CI]=0.20, [-2.08, 2.74]) or muscle strength (1.96, [-12.6, 16.6]). A sensitivity analysis yielded consistent results. Frailty was also not associated with hospital mortality (odds ratio 0.91, [0.28 to 2.93]). CONCLUSION: We found no association between pre-hospital frailty, physical function, strength, or mortality at hospital discharge in critically ill patients enrolled in an early rehabilitation trial. Larger sample sizes are needed to further explore the association of frailty with these outcomes at hospital discharge.

Protocol adherence for continuously titrated interventions in randomized trials: an overview of the current methodology and case study.

BACKGROUND: The standard definition for protocol adherence is the proportion of all scheduled doses that are delivered. In clinical research, this definition has several limitations when evaluating protocol adherence in trials that study interventions requiring continuous titration. DISCUSSION: Building upon a specific case study, we analyzed a recent trial of a continuously titrated intervention to assess the impact of different definitions of protocol deviations on the interpretation of protocol adherence. The OVATION pilot trial was an open-label randomized controlled trial of higher (75-80 mmHg) versus lower (60-65 mmHg) mean arterial pressure (MAP) targets for vasopressor therapy in shock. In this trial, potential protocol deviations were defined as MAP values outside the targeted range for >4 consecutive hours during vasopressor therapy without synchronous and consistent adjustments of vasopressor doses. An adjudication committee reviewed each potential deviation to determine if it was clinically-justified or not. There are four reasons for this contextual measurement and reporting of protocol adherence. First, between-arm separation is a robust measure of adherence to complex protocols. Second, adherence assessed by protocol deviations varies in function of the definition of deviations and the frequency of measurements. Third, distinguishing clinically-justified vs. not clinically-justified protocol deviations acknowledges clinically sensible bedside decision-making and offers a clear terminology before the trial begins. Finally, multiple metrics exist to report protocol deviations, which provides different information but complementary information on protocol adherence. CONCLUSIONS: In trials of interventions requiring continuous titration, metrics used for defining protocol deviations have a considerable impact on the interpretation of protocol adherence. Definitions for protocol deviations should be prespecified and correlated with between-arm separation, if it can be measured.

The monitoring of activity at home after total hip arthroplasty.

AIMS: Total hip arthroplasty (THA) has well known subjective benefits, but little is known objectively about the recovery of mobility in the early post-operative period. PATIENTS AND METHODS: A total of 33 patients aged > 60 years who underwent elective primary THA had their activity monitored for 30 days post-operatively using an at-home (Fitbit) ankle accelerometer. Their mean age was 70.7 years (61 to 86); 15 (45.5%) were female. The rate of compliance and the mean level of activity were determined. Comparisons between subgroups based on age, body mass index (BMI), surgical approach, and the destination of the patients when discharged were also performed. RESULTS: The mean compliance over the 30 days was 26.7 days (16 to 30; 89%) of use. The mean number of steps increased from 235 (5 to 1152) to 2563 (87 to 7280) (p < 0.001) between the first and the 30th post-operative day. Age < 70 years and an anterior surgical approach were significantly associated with higher levels of activity (1600 to 2400 (p = 0.016 to 0.031) and 1000 to 1800 (p = 0.017 to 0.037) more steps per day, respectively) between the second and the fourth week post-operatively. There was also a trend towards higher levels of activity in those who were discharged to their home rather than to a nursing facility (a mean of 1500 more steps per day, p = 0.02). BMI greater or less than 30 kg/m2 was not predictive of activity (p = 0.45 to 0.98). CONCLUSION: At-home remote mobility monitoring using existing commercially available technology is feasible in patients who have undergone THA. It showed a clear trend towards increased activity with the passage of time. Additionally, the remote device was able to detect differences in levels of activity clearly between patients in relation to variables of interest including age, BMI, surgical approach, and the destination of the patient at the time of discharge from hospital. Such monitoring may allow for the early identification and targeted intervention in patients who recover slowly. Cite this article: Bone Joint J 2016;98-B:1450-4.

Cytochromes P450: History, Classes, Catalytic Mechanism, and Industrial Application.

Cytochromes P450, a family of heme-containing monooxygenases that catalyze a diverse range of oxidative reactions, are so-called due to their maximum absorbance at 450nm, ie, "Pigment-450nm," when bound to carbon monoxide. They have appeal both academically and commercially due to their high degree of regio- and stereoselectivity, for example, in the area of active pharmaceutical ingredient synthesis. Despite this potential, they often exhibit poor stability, low turnover numbers and typically require electron transport protein(s) for catalysis. P450 systems exist in a variety of functional domain architectures, organized into 10 classes. P450s are also divided into families, each of which is based solely on amino acid sequence homology. Their catalytic mechanism employs a very complex, multistep catalytic cycle involving a range of transient intermediates. Mutagenesis is a powerful tool for the development of improved biocatalysts and has been used extensively with the archetypal Class VIII P450, BM3, from Bacillus megaterium, but with the increasing scale of genomic sequencing, a huge resource is now available for the discovery of novel P450s.

Fluid type and the use of renal replacement therapy in sepsis: a systematic review and network meta-analysis.

Fluid resuscitation, along with the early administration of antibiotics, is the cornerstone of treatment for patients with sepsis. However, whether differences in resuscitation fluids impact on the requirements for renal replacement therapy (RRT) remains unclear. To examine this issue, we performed a network meta-analysis (NMA), including direct and indirect comparisons, that addressed the effect of different resuscitation fluids on the use of RRT in patients with sepsis. The data sources MEDLINE, EMBASE, ACPJC, CINAHL and Cochrane Central Register were searched up to March 2014. Eligible studies included randomized trials reported in any language that enrolled adult patients with sepsis or septic shock and addressed the use of RRT associated with alternative resuscitation fluids. The risk of bias for individual studies and the overall certainty of the evidence were assessed. Ten studies (6664 patients) that included a total of nine direct comparisons were assessed. NMA at the four-node level showed that an increased risk of receiving RRT was associated with fluid resuscitation with starch versus crystalloid [odds ratio (OR) 1.39, 95% credibility interval (CrI) 1.17-1.66, high certainty]. The data suggested no difference between fluid resuscitation with albumin and crystalloid (OR 1.04, 95% CrI 0.78-1.38, moderate certainty) or starch (OR 0.74, 95% CrI 0.53-1.04, low certainty). NMA at the six-node level showed a decreased risk of receiving RRT with balanced crystalloid compared to heavy starch (OR 0.50, 95% CrI 0.34-0.74, moderate certainty) or light starch (OR 0.70, 95% CrI 0.49-0.99, high certainty). There was no significant difference between balanced crystalloid and saline (OR 0.85, 95% CrI 0.56-1.30, low certainty) or albumin (OR 0.82, 95% CrI 0.49-1.37, low certainty). Of note, these trials vary in terms of case mix, fluids evaluated, duration of fluid exposure and risk of bias. Imprecise estimates contributed to low confidence in most estimates of effect. Among the patients with sepsis, fluid resuscitation with crystalloids compared to starch resulted in reduced use of RRT; the same may be true for albumin versus starch.

The prevalence and impact of Fusarium head blight pathogens and mycotoxins on malting barley quality in UK.

Fusarium head blight (FHB) caused by Fusarium and Microdochium species can significantly affect the yield of barley grain as well as the quality and safety of malt and beer. The present study provides new knowledge on the impacts of the FHB pathogen complex on the malting and brewing quality parameters of naturally infected barley. Quantitative real-time PCR and liquid chromatography double mass spectrometry were used to quantify the predominant FHB pathogens and Fusarium mycotoxins, respectively, in commercially grown UK malting barley samples collected between 2007 and 2011. The predominant Fusarium species identified across the years were F. poae, F. tricinctum and F. avenaceum. Microdochium majus was the predominant Microdochium species in 2007, 2008, 2010 and 2011 whilst Microdochium nivale predominated in 2009. Deoxynivalenol and zearalenone quantified in samples collected between 2007 and 2009 were associated with F. graminearum and F. culmorum, whilst HT-2 and T-2, and nivalenol in samples collected between 2010 and 2011 correlated positively with F. langsethiae and F. poae, respectively. Analysis of the regional distribution and yearly variation in samples from 2010 to 2011 showed significant differences in the composition of the FHB species complex. In most regions (Scotland, the South and North of England) the harvest in 2010 had higher concentrations of Fusarium spp. than in 2011, although no significant difference was observed in the Midlands between the two years. Microdochium DNA was significantly higher in 2011 and in the North of England and Scotland compared to the South or Midlands regions. Pathogens of the FHB complex impacted negatively on grain yield and quality parameters. Thousand grain weight of malting barley was affected significantly by M. nivale and M. majus whilst specific weight correlated negatively with F. avenaceum and F. graminearum. To determine the impact of sub-acute infections of the identified Fusarium and Microdochium species on malting and brewing quality of naturally infected samples, selected malting barley cultivars (Optic, Quench and Tipple) were micromalted and subjected to malt and wort analysis of key quality parameters. F. poae and M. nivale decreased germinative energy and increased water sensitivity of barley. The fungal biomass of F. poae and F. langsethiae correlated with increased wort free amino nitrogen and with decreased extract of malt. DNA of M. nivale correlated with increased malt friability as well as decreased wort filtration volume. The findings of this study indicate that the impact of species such as the newly emerging F. langsethiae, as well as F. poae and the two non-toxigenic Microdochium species should be considered when evaluating the quality of malting barley.

Methodology for the development of antithrombotic therapy and prevention of thrombosis guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

BACKGROUND: To develop the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: ACCP Evidence-Based Clinical Practice Guidelines (AT9), the American College of Chest Physicians (ACCP) assembled a panel of clinical experts, information scientists, decision scientists, and systematic review and guideline methodologists. METHODS: Clinical areas were designated as articles, and a methodologist without important intellectual or financial conflicts of interest led a panel for each article. Only panel members without significant conflicts of interest participated in making recommendations. Panelists specified the population, intervention and alternative, and outcomes for each clinical question and defined criteria for eligible studies. Panelists and an independent evidence-based practice center executed systematic searches for relevant studies and evaluated the evidence, and where resources and evidence permitted, they created standardized tables that present the quality of the evidence and key results in a transparent fashion. RESULTS: One or more recommendations relate to each specific clinical question, and each recommendation is clearly linked to the underlying body of evidence. Judgments regarding the quality of evidence and strength of recommendations were based on approaches developed by the Grades of Recommendations, Assessment, Development, and Evaluation Working Group. Panel members constructed scenarios describing relevant health states and rated the disutility associated with these states based on an additional systematic review of evidence regarding patient values and preferences for antithrombotic therapy. These ratings guided value and preference decisions underlying the recommendations. Each topic panel identified questions in which resource allocation issues were particularly important and, for these issues, experts in economic analysis provided additional searches and guidance. CONCLUSIONS: AT9 methodology reflects the current science of evidence-based clinical practice guideline development, with reliance on high-quality systematic reviews, a standardized process for quality assessment of individual studies and the body of evidence, an explicit process for translating the evidence into recommendations, disclosure of financial as well as intellectual conflicts of interest followed by management of disclosed conflicts, and extensive peer review.(AU)

Substance P and vasoactive intestinal peptide are reduced in right transverse colon in pediatric slow-transit constipation.

BACKGROUND: Slow-transit constipation (STC) is recognized in children but the etiology is unknown. Abnormalities in substance P (SP), vasoactive intestinal peptide (VIP) and nitric oxide (NO) have been implicated. The density of nerve fibers in circular muscle containing these transmitters was examined in colon from children with STC and compared to other pediatric and adult samples. METHODS: Fluorescence immunohistochemistry using antibodies to NO synthase (NOS), VIP and SP was performed on colonic biopsies (transverse and sigmoid colon) from 33 adults with colorectal cancer, 11 children with normal colonic transit and anorectal retention (NAR) and 51 with chronic constipation and slow motility in the proximal colon (STC). The percentage area of nerve fibers in circular muscle containing each transmitter was quantified in confocal images. KEY RESULTS: In colon circular muscle, the percentage area of nerve fibers containing NOS > VIP > SP (6 : 2 : 1). Pediatric groups had a higher density of nerve fibers than adults. In pediatric samples, there were no regional differences in NOS and VIP, while SP nerve fiber density was higher in sigmoid than proximal colon. STC children had lower SP and VIP nerve fiber density in the proximal colon than NAR children. Twenty-three percent of STC children had low SP nerve fiber density. CONCLUSIONS & INFERENCES: There are age-related reductions in nerve fiber density in human colon circular muscle. NOS and VIP do not show regional variations, while SP nerve fiber density is higher in distal colon. 1/3 of pediatric STC patients have low SP or VIP nerve fiber density in proximal colon.

Decrease in nerve fibre density in human sigmoid colon circular muscle occurs with growth but not aging.

BACKGROUND: Studies in animals suggest that enteric neurons decrease in density or number with increasing age. Neurons containing nitric oxide (NO), vasoactive intestinal peptide (VIP) and Substance P (SP) have been implicated. In human large intestine, NO-utilizing neurons decrease during childhood or early adulthood but it is not known if the innervation of the muscle changes. This study examined the density of nerve fibres containing these transmitters in sigmoid colon circular muscle from children and adults. METHODS: Fluorescence immunohistochemistry using antibodies to neuronal NO synthase (nNOS), VIP and SP was performed on sigmoid colon from 18 adults with colorectal cancer, two children with familial adenomatous polyposis, and normal colon from nine children with Hirschsprung's disease. The percentage area of immunoreactive (IR) nerve fibres containing each transmitter in circular muscle was quantified in confocal images. KEY RESULTS: In the adult sigmoid colon circular muscle, the percentage area of nerve fibres containing nNOS>VIP>SP (6 : 2 : 1). Paediatric groups had significantly higher percentage area of nerve fibres containing nNOS, VIP or SP-IR than adults, with the decrease in nerve fibre density occurring from birth to 30 years. Circular muscle thickness increased between 12 and 30 years. Total nerve fibre area remained constant, while the muscle increased in thickness. CONCLUSIONS & INFERENCES: In human sigmoid colon circular muscle, there are reductions in nNOS-, VIP- and SP-IR nerve fibre density with growth from newborn to late adolescence but little further change with aging. The reduction in nerve density is due to an increase in circular muscle thickness rather than a loss of nerve fibres.

Anomaly detection using temporal data mining in a smart home environment.

OBJECTIVES: To many people, home is a sanctuary. With the maturing of smart home technologies, many people with cognitive and physical disabilities can lead independent lives in their own homes for extended periods of time. In this paper, we investigate the design of machine learning algorithms that support this goal. We hypothesize that machine learning algorithms can be designed to automatically learn models of resident behavior in a smart home, and that the results can be used to perform automated health monitoring and to detect anomalies. METHODS: Specifically, our algorithms draw upon the temporal nature of sensor data collected in a smart home to build a model of expected activities and to detect unexpected, and possibly health-critical, events in the home. RESULTS: We validate our algorithms using synthetic data and real activity data collected from volunteers in an automated smart environment. CONCLUSIONS: The results from our experiments support our hypothesis that a model can be learned from observed smart home data and used to report anomalies, as they occur, in a smart home.

Attrition from heart transplant waiting list for patients on ventricular assist devices is not affected by desensitization strategies.

BACKGROUND: Ventricular assist device (VAD) patients, who are commonly sensitized, can be successfully transplanted using strategies aimed at diminishing antibody burden. However, the impact of these therapies on outcomes for VAD patients on the waiting list is ill-defined. The following study was conducted to ascertain the relationship between desensitization therapies and attrition rate from the waiting list for VAD patients. METHODS: The VAD patients listed between July 1996 and June 2002 were used for this report. Transplant and inpatient pharmacy databases were queried for demographics, date of transplantation, degree of allosensitization, use of desensitization therapy, immunosuppressive strategies, and specific causes of death. RESULTS: Among 232 patients listed for heart transplantation who required bridging to transplantation with a VAD, 79 (34%) died while on the waiting list. Common causes of death included multisystem organ failure in 32 (40.5%), sepsis in 19 (24.0%), and stroke in 10 (12.6%) patients. While nearly 50% of these patients were sensitized at listing, only 5 (6.3%) patients received desensitization therapy following VAD implantation. Therapies included mycophenolate mofetil in 3 (3.7%) and IVIG in 2 (2.5%) patients. Not a single patient underwent plasmapheresis or OKT3 therapy. CONCLUSION: For patients bridged to heart transplantation with a VAD, attrition from the waiting list was associated with factors other than desensitization or induction regimens.

Alemtuzumab induction and sirolimus plus mycophenolate mofetil maintenance for CNI and steroid-free kidney transplant immunosuppression.

We performed a pilot study in which 22 kidney recipients (14 LD: 8 DCD) were given alemtuzumab induction (30 mg day 0 and 1), steroids (500 mg mp day 0 and 1, none thereafter), mycophenolate mofetil (MMF) maintenance (500 mg b.i.d) and sirolimus (concentration controlled 8-12 ng/mL). With a mean follow-up of 15.9 months, patient survival is (21/22) 96% and graft survival (19/22) 87%. Acute rejections occurred in (8) 36.3% (two humoral). Of 19 surviving grafts, 18 (95%) remain steroid and 15 (79%) CNI-free. At 1 year, mean creatinine was 1.43 mg/dL. Overall infection rates were low, but 2 patients developed severe acute respiratory distress syndrome (ARDS) at month 3 and 7, respectively, resulting in mortality in one and a graft loss in the other. No cancer or PTLD was observed. Leukopenia was common and MMF dose was reduced or eliminated in 6/22 (27%) patients. The reported higher than expected rate of acute rejection, leukopenia and possible pulmonary toxicity suggests excessive morbidity. Modifications such as an initial period of CNI use should be considered.

Safety Climate Survey: reliability of results from a multicenter ICU survey.

BACKGROUND: It is important to understand the clinical properties of instruments used to measure patient safety before they are used in the setting of an intensive care unit (ICU). METHODS: The Safety Climate Survey (SCSu), an instrument endorsed by the Institute for Healthcare Improvement, the Safety Culture Scale (SCSc), and the Safety Climate Mean (SCM), a subset of seven items from the SCSu, were administered in four Canadian university affiliated ICUs. All staff including nurses, allied healthcare professionals, non-clinical staff, intensivists, and managers were invited to participate in the cross sectional survey. RESULTS: The response rate was 74% (313/426). The internal consistency of the SCSu and SCSc was 0.86 and 0.80, respectively, while the SCM performed poorly at 0.51. Because of poor internal consistency, no further analysis of the SCM was therefore performed. Test-retest reliability of the SCSu and SCSc was 0.92. Out of a maximum score of 5, the mean (SD) scores of the SCSu and SCSc were 3.4 (0.6) and 3.4 (0.7), respectively. No differences were noted between the three medical-surgical and one cardiovascular ICU. Managers perceived a significantly more positive safety climate than other staff, as measured by the SCSu and SCSc. These results need to be interpreted cautiously because of the small number of management participants. CONCLUSIONS: Of the three instruments, the SCSu and SCSc appear to be measuring one construct and are sufficiently reliable. Future research should examine the properties of patient safety instruments in other ICUs, including responsiveness to change, to ensure that they are valid outcome measures for patient safety initiatives.

Early and late rejection and HLA sensitization at the time of heart transplantation in patients bridged with left ventricular assist devices.

Over the years, the frequency of heart transplant candidates with HLA sensitization has increased as a result of the number of patients bridged to transplant using left ventricular assist devices (LVAD). Here we have examined 119 patients who were bridged to transplant with LVAD for a relationship between HLA antibodies and early (30 days) and late (2 years or more) rejection, as evidenced by endomyocardial biopsies. Both cytotoxic panel-reactive antibody reactions against a panel of T lymphocytes (T-PRA) and the percentage of transplants that occurred across a positive class I flow cross-match were examined. Biopsies were scored using ISHLT criteria. At 30 days, patients who had a biopsy grade of 0 had a mean T-PRA at transplant of 2.2%, while the mean PRAs of the other biopsy grades were significantly higher (P < .001). A similar pattern was seen with the highest biopsy results at 2 years or later (P < .001). None of the patients who had a grade 0 biopsy at 30 days posttransplant had a positive flow cytometry class I cross-match (P = .02), although the same pattern did not occur later due to a small number of patients (n = 3) who had negative biopsies. Thus, when biopsy results were examined early or late posttransplant, patients with negative biopsy results tended to have less HLA sensitization. While the methods of HLA sensitization involve humoral responses, more aggressive immunosuppression might be warranted to attempt to reduce cellular rejection posttransplant if HLA class I antibodies are present at the time of transplant.

Agreement of aspiration tests using barium videofluoroscopy, salivagram, and milk scan in children with cerebral palsy.

To study the agreement between three tests for aspiration, barium videofluoroscopy, salivagram, and milk scan we studied 63 children with severe non-ambulant spastic quadriplegic cerebral palsy (CP) aged 14 months to 16 years (32 males, 31 females). The salivagram was most frequently positive (56%, 95% confidence interval 43 to 68%); the next most frequently positive was barium videofluoroscopy when aspiration was defined as the presence of either laryngeal penetration of material or frank aspiration (39%, 95% confidence interval 26 to 53%). The milk scan was rarely positive (6%, 95% confidence interval 2 to 16%). Agreement between the tests of aspiration was poor. The maximum agreement (kappa=0.20) was between aspiration as diagnosed with the salivagram and by barium videofluoroscopy. Positive tests for aspiration are frequent in children with severe CP. Frequency varies widely depending on the investigation used. There is poor agreement between tests used for the diagnosis of aspiration. This information is of importance in assessing the significance of test results.

Neither baseline tests of molecular hypercoagulability nor D-dimer levels predict deep venous thrombosis in critically ill medical-surgical patients.

OBJECTIVE: Predicting patients who are harboring asymptomatic deep venous thrombosis (DVT), or who are at particular risk of developing DVT, is a desirable clinical goal since prevention or early treatment of DVT might reduce the risk of fatal pulmonary embolism. Thus validation of simple laboratory tests that reliably predict venous thromboembolism (VTE) would be clinically very important. Tests that might be useful for these applications include markers of hypercoagulability (predicting patients at risk of DVT) and D-dimer (predicting which patients may have acute DVT). METHODS: In a prospective cohort study we measured a panel of hypercoagulability markers at the time of ICU admission, and six commercial D-dimer assays were performed serially during the ICU stay in medical-surgical ICU patients who were screened for DVT with biweekly lower limb compression ultrasonography. Ultrasonography was also performed at the time of any clinically suspected DVT events. We matched cases with DVT with controls without DVT for length of stay in the ICU to generate receiver operating characteristics (ROC) curves. RESULTS: One hundred ninety-seven patients were enrolled. Blood was collected on a total of 763 occasions (median number of occasions per patient: 3, range 1-21). None of the assays predicted DVT, as indicated by the areas under the ROC curves, that did not differ significantly from 50%. CONCLUSION: In critically ill patients, neither tests of hypercoagulability nor D-dimer levels predict patients at risk of DVT and thus they should not be used to guide diagnostic testing for DVT.

Survival beyond 10 years following heart transplantation: The Cleveland Clinic Foundation experience.

BACKGROUND: Long-term survival after heart transplantation is a desirable although challenging goal. METHODS: We analyzed clinical outcomes in the cohort of 170 patients who have undergone heart transplantation at The Cleveland Clinic Foundation and survived >10 years. RESULTS: We found 10-year and 15-year survival rates of 54% and 41%, respectively, in these patients, but there was also a high incidence of complications, such as hypertension, renal dysfunction, transplant vasculopathy, and malignancy. CONCLUSIONS: Long-term survival following cardiac transplantation is possible although complications are frequent. Beyond 10 years, malignancy is a major cause of death.

Donor intracranial bleeding is associated with advanced transplant coronary vasculopathy: evidence from intravascular ultrasound.

OBJECTIVES: We evaluated the impact of spontaneous intracranial bleeding (ICB) in the donor on transplant coronary vasculopathy using serial intravascular ultrasound examinations. MATERIALS AND METHODS: Between January 1995 and December 2000, 72 recipients underwent cardiac transplantation from donors who had experienced spontaneous ICB (ICB group). Their findings using serial intravascular ultrasound analysis at baseline (within 1 month) and 1 year after transplantation were compared with 90 recipients who had undergone transplantation from trauma donors (trauma group). RESULTS: Compared with the Trauma group, the ICB group showed increased coronary intimal thickness (0.55 +/- 0.33 vs 0.39 +/- 0.3 mm; P = .034), plaque volume (3.84 +/- 2.5 vs 2.28 +/- 1.65 mm(3); P = .015) and plaque burden (7.4 vs 2%) at 1 year after transplantation. CONCLUSIONS: Donor spontaneous ICB is associated with significantly increased coronary vasculopathy.