Acute kidney injury after colorectal surgery with prophylactic ureteral stents.

BACKGROUND: After colorectal surgery, acute kidney injury (AKI) results from a complex interplay of multiple independent causes and preventive measures that occur during the hospitalization. Prophylactic stenting for ureter identification has been identified as a potential cause, but the evidence is conflicting, possibly because of differing baseline characteristics and procedure-related approaches. OBJECTIVE: This retrospective cohort study assesses the role of stents in the etiology of AKI after determining the independent predictors of AKI. METHODS: From a population of 1224 consecutive colorectal patients (from 8/1/2016 through 12/31/2021), 382 (31.2%) received ureteral stents, and propensity score matching was used to create stented and control groups. Emergent cases and patients with sepsis were excluded from the analysis. Previously identified independent predictors of AKI, minimally invasive procedures, and a history of diabetes mellitus were used as criteria to create two balanced groups. RESULTS: Baseline demographic characteristics and procedure-related factors baseline factors were similar between the groups. There was no difference in the rate of AKI between stented patients and controls (P = 0.82), nor was there any difference in postoperative complications, such as chronic renal insufficiency (CRI, P = 0.49), average postoperative creatinine (P = 0.67), urinary tract infections (UTI, P = 0.82), any postoperative infection (P = 0.48), in-hospital complications (P = 1.00), length of stay (LOS, P = 0.15), and 30-day readmissions (P = 0.79). CONCLUSIONS: In a population of patients where stenting was frequently employed, ureter stents placed for identification did not appear to cause AKI or AKI-related complications.

Systemic inflammation and acute kidney injury after colorectal surgery.

BACKGROUND: In this retrospective review, the relative importance of systemic inflammation among other causes of acute kidney injury (AKI) was investigated in 1224 consecutive colorectal surgery patients. A potential benefit from reducing excessive postoperative inflammation on AKI might then be estimated. METHODS: AKI was determined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The entire population (mixed group), composed of patients with or without sepsis, and a subpopulation of patients without sepsis (aseptic group) were examined. Markers indicative of inflammation were procedure duration, the first postoperative white blood cell (POD # 1 WBC) for the mixed population, and the neutrophil-to-lymphocyte ratio (POD #1 NLR) for the aseptic population. Multivariable logistic regression was then performed using significant (P < 0.05) predictors. The importance of inflammation among independent predictors of AKI and AKI-related complications was then assessed. RESULTS: AKI occurred in 24.6% of the total population. For the mixed population, there was a link between inflammation (POD # 1 WBC) and AKI (P = 0.0001), on univariate regression. Medications with anti-inflammatory properties reduced AKI: ketorolac (P = 0.047) and steroids (P = 0.038). Similarly, in an aseptic population, inflammation (POD # 1 NLR) contributed significantly to AKI (P = 0.000). On multivariable analysis for the mixed and aseptic population, the POD #1 WBC and the POD #1 NLR were independently associated with AKI (P = 0.000, P = 0.022), as was procedure duration (P < 0.0001, P < 0.0001). Inflammation-related parameters were the most significant contributors to AKI. AKI correlated with complications: postoperative infections (P = 0.016), chronic renal insufficiency (CRI, P < 0.0001), non-infectious complications (P = 0.010), 30-day readmissions (P = 0.001), and length of stay (LOS, P < 0.0001). Inflammation, in patients with or without sepsis, was similarly a predictor of complications: postoperative infections (P = 0.002, P = 0.008), in-hospital complications (P = 0.000, P = 0.002), 30-day readmissions (P = 0.012, P = 0.371), and LOS (P < 0.0001, P = 0.006), respectively. CONCLUSIONS: Systemic inflammation is an important cause of AKI. Limiting early postsurgical inflammation has the potential to improve postoperative outcomes.

Treatment of Severe Hyperglycemia in Patients Without Diabetes After Colorectal Surgery.

Background: Several studies have suggested that intravenous insulin therapy for post-operative hyperglycemia improves outcomes after colorectal surgery. Despite the potential benefit, there is a reluctance to use this approach in patients without diabetes mellitus because of an unproven benefit and the potential for hypoglycemia. In this study, we examined whether sliding-scale insulin is sufficient to improve outcomes or if stricter glucose control is necessary. Patients and Methods: Of 1,064 consecutive colorectal surgery patients between August 2016 and December 2021, 478 patients without diabetes mellitus had an average of 6.4 ± 3.1 glucose samples taken within 48 hours after surgery. Sixty-six percent of patients with severe hyperglycemia (glucose ≥180 mg/dL) received sliding-scale insulin. Complication rates and effects of insulin were examined. Results: Severe hyperglycemia was associated with a higher total infection rate (p < 0.002), National Healthcare Safety Network-reported infections (NHSN; p < 0.026), total complications (p < 0.001), and length of stay (LOS; p < 0.000). Sliding-scale insulin did not lower the risk of infection or other complications. Hypoglycemia (glucose <70 mg/dL) occurred in 3.5% of patients, but was not related to insulin use, and was predictable with clinical variables: albumin (p < 0.032), operative duration (p < 0.012), and average post-operative glucose (p < 0.002; area under the curve [AUC], 0.86). Conclusions: Our data confirm that severe post-operative hyperglycemia in patients without diabetes mellitus after colorectal surgery is associated with complications. Sliding-scale insulin was safe but not effective. Treatment before severe hyperglycemia is reached, not after its occurrence, may be beneficial.

Closed Incisional Negative Pressure Therapy Reduces Perineal Wound Complications After Abdominoperineal Resection.

BACKGROUND: Perineal wound complications after abdominoperineal resection continue to be a significant challenge. Complications, ranging from 14% up to 60%, prolong hospitalization, increase risk of readmission and reoperation, delay the start of adjuvant therapy, and place psychological stress on the patient and family. OBJECTIVE: This study aimed to evaluate the impact of closed incision negative pressure therapy on perineal wound healing. DESIGN: This was a retrospective study. SETTINGS: The study was conducted in an academic community hospital. PATIENTS: Patients who underwent abdominoperineal resection from 2012 to 2020 were included. MAIN OUTCOME MEASURES: Perineal wound complications within 30 and 180 days were the primary outcome measures. RESULTS: A total of 45 patients were included in the study. Of these, 31 patients were managed with closed incision negative pressure therapy. The overall perineal wound complications were less frequent in the closed incision negative pressure therapy group (10/31; 32.2%) compared to the control group (10/14; 71.4%; = 5.99 [ p = 0.01]). In the closed incision negative pressure therapy group, 2 patients (20%) did not heal within 180 days and no patient required reoperation or readmission. In the control group, 4 patients (44%) had not healed at 180 days and 1 patient required flap reconstruction. When the effect of other variables was controlled, closed incision negative pressure therapy resulted in an 85% decrease in the odds of wound complications (adjusted OR 0.15 [95% CI, 0.03-0.60]; p = 0.01). LIMITATIONS: The nonrandomized nature and use of historical controls in this study are its limitations. CONCLUSIONS: The ease of application and the overall reduction in the incidence and severity of complications may offer an option for perineal wound management and possibly obviate the need for more expensive therapies. Further prospective controlled trials are required to effectively study its efficacy. See Video Abstract at http://links.lww.com/DCR/B895 . LA TERAPIA POR PRESIN NEGATIVA INCISIONAL CERRADA, REDUCE LAS COMPLICACIONES DE LA HERIDA PERINEAL DESPUS DE LA RESECCIN ABDOMINOPERINEAL: ANTECEDENTES:Las complicaciones de la herida perineal, después de la resección abdominoperineal, continúan siendo un desafío importante. Las complicaciones, que van desde el 14% hasta el 60%, prolongan la hospitalización, aumentan el riesgo de reingreso y reintervención, retrasan el inicio de la terapia adyuvante y generan estrés psicológico en el paciente y su familia.OBJETIVO:Evaluar el impacto de la terapia de presión negativa con incisión cerrada en la cicatrización de heridas perineales.DISEÑO:Estudio retrospectivo.ENTORNO CLINICO:Hospital comunitario académico.PACIENTES:Se incluyeron pacientes sometidos a resección abdominoperineal entre 2012 y 2020.PRINCIPALES MEDIDAS DE VALORACION:Las complicaciones de la herida perineal dentro de los 30 y 180 días fueron las principales medidas de valoración.RESULTADOS:Se incluyeron en el estudio a un total de 45 pacientes. De estos, 31 pacientes fueron tratados con terapia de presión negativa con incisión cerrada. Las complicaciones generales de la herida perineal fueron menos frecuentes en el grupo de terapia de presión negativa con incisión cerrada (10/31, 32,2%) en comparación con el grupo de control (10/14, 71,4%) (X_1 ^ 2 = 5,99 [ p = 0,01]). En el grupo de terapia de presión negativa con incisión cerrada, dos pacientes (20%) no cicatrizaron en 180 días y ningún paciente requirió reintervención o readmisión. En el grupo de control, cuatro pacientes (44%) no habían cicatrizado a los 180 días y un paciente requirió reconstrucción con colgajo. Cuando se controló el efecto de otras variables, la terapia de presión negativa con incisión cerrada resultó con una disminución del 85% en las probabilidades de complicaciones de la herida (OR ajustado, 0.15 [IC 95%, 0,03-0,60]; p = 0,01).LIMITACIONES:La naturaleza no aleatoria y el uso de controles históricos en este estudio, son limitaciones.CONCLUSIÓNES:La facilidad de aplicación, reducción general de la incidencia y gravedad de las complicaciones, pueden ofrecer una opción para el manejo de las heridas perineales y posiblemente obviar la necesidad de tratamientos más costosos. Se necesitan más ensayos controlados prospectivos para efectivamente estudiar la eficacia. Consulte Video Resumen en http://links.lww.com/DCR/B895 . (Traducción-Dr. Fidel Ruiz Healy ).

Postoperative Hyperglycemia in Patients with and without Diabetes After Major Joint Replacement: The Impact of an Enhanced Glucose Management Program.

BACKGROUND: Perioperative hyperglycemia can have an even more detrimental effect on postoperative outcomes in patients without diabetes than in patients with diabetes, but it has not been established if the treatment of patients without diabetes is safe and effective. We hypothesized that sliding-scale insulin for severe postoperative hyperglycemia (glucose ≥180 mg/dL) could lower mean postoperative glucose levels and minimize short-term complications in patients without diabetes undergoing major joint replacement. METHODS: In a prospective study group, 1,398 consecutive patients, with and without diabetes, undergoing joint replacement were monitored and treated for hyperglycemia and were compared with 886 historical, less frequently monitored controls. The primary outcome was the mean glucose level in patients with and without diabetes within 48 hours after the surgical procedure. Two secondary outcomes could be examined only in the prospective study group, which, by design, had much more frequent glucose sampling and insulin use than the historical controls. First, the contribution of comorbidities and procedural factors to postoperative hyperglycemia in patients without diabetes was assessed with multivariable linear regression. Second, the ability of insulin treatment to reduce complications in patients without diabetes who developed hyperglycemia was evaluated. RESULTS: In comparison with 886 historical controls, enhanced glucose management lowered the mean glucose (and standard deviation) from 129 ± 28 mg/dL to 123 ± 23 mg/dL for patients without diabetes (p = 0.041). Multivariable linear regression revealed factors that contributed to elevated mean glucose in patients without diabetes: preoperative fasting glucose (p < 0.001), perioperative steroid use (p < 0.001), general anesthesia (p < 0.001), procedure duration (p = 0.003), and transfusion (p 0.008). Of 968 patients without diabetes, 203 developed severe hyperglycemia. The recommended insulin coverage was given to 129 of these patients, and 74 patients did not receive it for various clinical reasons. Insulin treatment reduced the frequency of positive cultures from any site (p = 0.025) and a composite of positive cultures and readmissions (p = 0.006) in comparison with no insulin treatment. No patient without diabetes who received insulin experienced mild or severe hypoglycemia. CONCLUSIONS: Postoperative hyperglycemia is frequent in patients without diabetes after orthopaedic surgery, but an enhanced glucose management program can lower mean postoperative glucose levels. The treatment of hyperglycemia in patients without diabetes reduced short-term complications and was associated with minimal side effects. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

The no-touch saphenous vein is an excellent alternative conduit to the radial artery 8 years after coronary artery bypass grafting: A randomized trial.

BACKGROUND: In 2004, a prospective randomized trial demonstrated that after 3 years, saphenous veins (SVs) harvested with a no touch (NT) technique had a greater patency than radial grafts for coronary bypass surgery. Here we report the 8-year follow-up data of this trial. METHODS: The trial included 108 patients undergoing coronary artery bypass grafting (CABG). Each patient was assigned to receive 1 NT SV and 1 radial artery (RA) graft to either the left or right coronary territory to complement the left internal thoracic artery (LITA). Sequential grafting was common, so overall graft patency as well as the patency of each anastomosis were assessed. RESULTS: Angiography was performed in 84 patients (78%) at mean of 97 months postoperatively. Graft patency were high and similar for both NT and RA: 86% for NT versus 79% for RA (P = .22). The patency of coronary anastomoses was significantly higher with the NT SV grafts (91% vs 81%; P = .046). The NT grafts also had excellent patency in coronary arteries with <90% stenosis (93% patency) and in coronary arteries of small diameter (87% patency) or with mild calcification (88% patency). Patency for the LITA was 92%. CONCLUSIONS: NT SV grafts have excellent patency similar to that of RA grafts after 8 years. In addition, NT SV grafts can be used in situations that are not ideal for RA grafts.

The no-touch saphenous vein graft in elderly coronary bypass patients with multiple comorbidities is a promising conduit to substitute the left internal thoracic artery.

OBJECTIVES: We investigated the patency rates of no-touch saphenous vein grafts anastomosed to the left anterior descending artery compared with the left internal thoracic artery. Further, we compared the patency of no-touch vein grafts to the left anterior descending artery with the patency of no-touch vein grafts to other coronary arteries. METHODS: Of 2635 consecutive patients undergoing coronary artery bypass grafting between 2003 and 2008, 168 (6.3%) were given at least a saphenous vein graft to the left anterior descending artery to avoid harvesting complications in high-risk patients or in response to a left internal thoracic artery injury. A total of 97 patients were consecutively included after informed consent. A clinical examination and computed tomography angiography were performed on 91 patients at a mean of 6 (4-9) years. RESULTS: The mean age of patients was 75.6 ± 8.5 years. Postoperatively, 88.7% of patients (86/97) were free of angina. The 91 examined patients had 163 grafts with 286 distal anastomoses. Crude patency, according to distal anastomoses, was 94.4% (270/286). The patency of single versus sequential no-touch vein grafts to the left anterior descending artery was 98% (50/51) versus 92.5% (37/40). The total patency rate was 95.6% (87/91), similar to the reported patency rate for the left internal thoracic artery. The no-touch grafts to the left anterior descending artery versus other coronaries had a patency of 95.6% (87/91) versus 93.8% (183/195), a high similarity confirmed by an equivalence analysis. CONCLUSIONS: In elderly coronary bypass patients with multiple comorbidities, a no-touch saphenous vein graft is a promising substitute for the left internal thoracic artery.

Development of a new statewide eating disorder service: The role of evidence in a real world setting.

OBJECTIVE: There are three aims of this report. First, to describe how research evidence informed a service development rationale for a new statewide eating disorder service (SEDS) for people aged 15 years and older. Second, to examine the profile of people accessing SEDS in the first 2 years of its operation with respect to the three broad dimensions: illness stage, illness severity, and previous history of treatment. Finally, to examine which patient characteristics resulted in the recommendation of ongoing treatment contact with SEDS. METHOD: Over a 2-year period (July 2014 to July 2016) 292 people were referred to the service, 171 (59%) who consented to have their data used in research. RESULTS: Half of the referrals related to anorexia nervosa (AN; 51.2%), with the remainder split between bulimia nervosa (25.3%) and other specified feeding and eating disorders (23.5%); 65.9% had previously received treatment for an eating disorder. The initial information about the service was typically provided by the general practitioner/primary care physician. Compared with any other eating disorder diagnosis, people with AN were three times more likely to be recommended to retain treatment contact with SEDS. DISCUSSION: Service development informed by research evidence, clinical expertise, and consideration of patients' characteristics, values, and circumstances, allows for a flexible but accountable development strategy.

The no-touch vein graft for coronary artery bypass surgery preserves the left ventricular ejection fraction at 16†years postoperatively: long-term data from a longitudinal randomised trial.

OBJECTIVES: To assess the left ventricular heart function and the clinical outcome 16 years after coronary artery bypass surgery. DESIGN: In a randomised trial, the no-touch (NT) vein graft in coronary artery bypass surgery has shown a superior patency rate, a slower progression of atherosclerosis and better clinical outcome compared to the conventional (C) vein graft at 8.5 years. All patients at mean time 16 years were offered an echocardiographic and clinical examination. RESULTS: In the NT-group 34 patients and in the C-group 31 patients underwent an echocardiography examination. A significantly better left ventricle ejection fraction was seen in the NT-group compared to the C-group (57.9% vs 49.4%; p=0.011). The size of the left atrium in NT was 21.7 cm(2) compared to 23.9 cm(2) in C; p=0.034. No patient in NT had atrial fibrillation compared to five patients in C (p=0.021). Patients with a brain natriuretic peptide value (BNP) ≥150 was 30% in NT compared to 38% in C. Total mortality was 25% in NT vs 27% in C. Cardiac-related deaths were 8% and 12% in NT and C respectively. CONCLUSIONS: The NT vein graft preserves the left ventricular ejection fraction after 16 years. A smaller left atrium, a lower BNP and no atrial fibrillation indicates an improved diastolic left ventricular function in the NT-group. TRIAL REGISTRATION: The study is registered with clinicaltrials.gov (NCT01686100) and The Research and Development registry in Sweden (no. 102841).

"No-touch" versus "endo" vein harvest: early patency on symptom-directed catheterization and harvest site complications.

OBJECTIVE: "No-touch" (NT) saphenous vein harvesting preserves the adventitial vasa vasorum, prevents medial ischemia, and is associated with an improved short-term and long-term vein graft patency. It may also be associated with a higher rate of harvest site complications. Endovascular vein harvesting (endo-vein) has a low rate of harvest site complications but also a tendency toward a lower patency rate. METHODS: During a 2-year period (2011-2012), we compared the vein graft patency at symptom-directed cardiac catheterization as well as wound complication rates in 210 patients who received either NT (87 patients) or endo-vein (123 patients). RESULTS: The recatheterization rate for the two groups was similar: 9 (10.3%) of 87 of the NT patients versus 11 (9.0%) of 123 of the endo-vein patients. There was a significant difference in vein graft patency between the groups: 15 (94%) of 16 NT vein grafts were patent versus 6 (27%) of 22 of endo-veins (P < 0.02). The endo-vein graft patency during this 2-year period was similar to the total endo-vein patency (37%) during a 4-year period. A comparison between a more experienced and a less experienced harvester revealed no difference in patency rate. Harvest site complications were significantly higher with the NT harvest: 18% of the NT patients requiring vacuum-assisted wound closure or intravenous antibiotics versus 2% of the endo-vein patients (P < 0.0001). The application of platelet-rich plasma did not significantly lower wound complication rates (P = 0.27). CONCLUSIONS: These results suggest that NT vein harvesting may be associated with improved graft patency, but methods should be developed to lower wound complication rates.

Adding an endovascular aortic surgery program to a rural regional medical centre.

BACKGROUND: Abdominal aortic aneurysms requiring surgical intervention are generally treated by endovascular means. Such procedures are not always offered in rural hospitals, possibly leaving patients underserved. We reviewed our experience initiating an endoaortic surgery program. METHODS: A surgeon in a rural centre was credentialed to perform endovascular aortic aneurysm repair through collaboration with a university centre and was proctored locally for the first 5 abdominal aneurysm repairs. Web-based image storage was used to review complex cases as part of an ongoing partnership. Referred patients were screened for multiple aneurysms and underwent long-term monitoring. RESULTS: In all, 160 patients were evaluated for 176 aortic pathologies. Twenty-five patients (17 men) aged 55-89 years underwent 26 endovascular abdominal (n = 23) or thoracic (n = 3) aortic procedures. Emergent endovascular procedures were not performed. There were no operative deaths, requirements for dialysis or conversions to open repair. Two endoleaks required early reintervention. The median length of stay in hospital for endovascular procedures was 2.5 days. Chronic endoleaks were observed in 7 patients. An additional 8 patients underwent open abdominal aneurysm repair locally and 15 patients were referred to the university program. CONCLUSION: Creation of an endovascular aortic surgery program in a rural hospital is feasible through collaboration with a high-volume centre. Patient safety is enhanced by obtaining second opinions using web-based image review. Most interventions are for abdominal aortic aneurysms, but planning for a comprehensive aortic clinic is preferable.

CONTEXTE: Les anévrismes de l'aorte abdominale justiciables d'une intervention chirurgicale sont généralement traités par voie endovasculaire. Ce type d'intervention n'est toutefois pas toujours pratiqué dans les hôpitaux ruraux. Les patients peuvent donc s'en trouver moins bien desservis. Nous avons passé en revu notre expérience après la mise sur pied d'un programme de chirurgie endoaortique. MÉTHODES: Grâce à une collaboration avec un centre universitaire, un chirurgien d'un centre rural a reçu l'agrément nécessaire pour effectuer la réparation endovasculaire des anévrismes de l'aorte et il a été supervisé localement pour les 5 premières réparations d'anévrisme de l'aorte abdominale. Une banque d'images sur le Web a permis de passer en revue des cas complexes dans le cadre d'un partenariat continu. On a fait subir aux patients adressés en consultation un dépistage d'anévrismes multiples et ils ont fait l'objet d'un suivi à long terme. RÉSULTATS: En tout, 160 patients ont été examinés pour 176 anomalies aortiques. Vingt-cinq patients (17 hommes) âgés de 55 à 89 ans ont subi 26 interventions endovasculaires de l'aorte abdominale (n = 23) ou thoracique (n = 3). Aucune autre intervention endovasculaire n'a été effectuée. On n'a eu à déplorer aucun décès en lien avec les interventions, aucun recours à la dialyse ni conversion vers une chirurgie ouverte. Deux endofuites ont nécessité une réintervention précoce. La durée médiane du séjour hospitalier dans les cas d'intervention endovasculaire a été de 2,5 jours. Des endofuites chroniques ont été observées chez 7 patients. Huit autres patients ont subi une réparation ouverte d'anévrisme abdominal localement et 15 patients ont été référés au programme universitaire. CONCLUSION: La création d'un programme de chirurgie de l'aorte endovasculaire dans un hôpital rural est réalisable grâce à une collaboration avec un centre dont le volume d'interventions est élevé. La sécurité des patients est renforcée par l'obtention de secondes opinions facilitées par une banque d'images sur le Web. La plupart des interventions concernent des anévrismes de l'aorte abdominale, mais il est préférable de planifier la mise en place d'une clinique où on pourrait intervenir sur toutes les portions de l'aorte.

The no-touch saphenous vein as the preferred second conduit for coronary artery bypass grafting.

BACKGROUND: Injury incurred while saphenous veins are being obtained results in poor graft patency and impairs the results of coronary artery bypass grafting. A novel method of obtaining veins, the no-touch technique, has shown improved long-term saphenous vein graft patency. METHODS: This randomized trial included 108 patients undergoing coronary artery bypass grafting and compared the patency of no-touch saphenous vein with that of radial artery grafts. Each patient was assigned to receive one no-touch saphenous vein and one radial artery graft to either the left or the right coronary territory to complement the left internal thoracic artery. RESULTS: Angiography was performed in 99 patients (92%) at a mean of 36 months postoperatively. Graft and grafted coronary artery patency was evaluated. The patency of grafts for no-touch saphenous vein and radial artery was 94% versus 82% (p = 0.01), respectively. The patency of coronary arteries grafted with no-touch saphenous vein and radial artery grafts was 95% versus 84% (p = 0.005), respectively. Eighty-nine of 96 (93%) left internal thoracic artery grafts were patent. CONCLUSIONS: No-touch saphenous vein grafts showed a significantly higher patency rate than the radial artery grafts and the patency was comparable to the patency for left internal thoracic artery grafts. This highlights the improvement in saphenous vein graft quality with the no-touch technique and increases the number of situations in which saphenous veins may be preferable to radial artery grafts as conduits in coronary artery bypass grafting.

Entropic unfolding of DNA molecules in nanofluidic channels.

Single DNA molecules confined to nanoscale fluidic channels extend along the channel axis in order to minimize their conformational free energy. When such molecules are forced into a nanoscale fluidic channel under the application of an external electric field, monomers near the middle of the DNA molecule may enter first, resulting in a folded configuration with less entropy than an unfolded molecule. The increased free energy of a folded molecule results in two effects: an increase in extension factor per unit length for each segment of the molecule, and a spatially localized force that causes the molecule to spontaneously unfold. The ratio of this unfolding force to hydrodynamic friction per DNA contour length is measured in nanochannels with two different diameters.

Conformation, length, and speed measurements of electrodynamically stretched DNA in nanochannels.

A method is presented to rapidly and precisely measure the conformation, length, speed, and fluorescence intensity of single DNA molecules constrained by a nanochannel. DNA molecules were driven electrophoretically from a nanoslit into a nanochannel to confine and dynamically elongate them beyond their equilibrium length for repeated detection via laser-induced fluorescence spectroscopy. A single-molecule analysis algorithm was developed to analytically model bursts of fluorescence and determine the folding conformation of each stretched molecule. This technique achieved a molecular length resolution of 114 nm and an analysis time of around 20 ms per molecule, which enabled the sensitive investigation of several aspects of the physical behavior of DNA in a nanochannel. lambda-bacteriophage DNA was used to study the dependence of stretching on the applied device bias, the effect of conformation on speed, and the amount of DNA fragmentation in the device. A mixture of lambda-bacteriophage with the fragments of its own HindIII digest, a standard DNA ladder, was sized by length as well as by fluorescence intensity, which also allowed the characterization of DNA speed in a nanochannel as a function of length over two and a half orders of magnitude.

Activation of the canonical Wnt/beta-catenin pathway enhances monocyte adhesion to endothelial cells.

Monocyte adhesion to vascular endothelium has been reported to be one of the early processes in the development of atherosclerosis. In an attempt to develop strategies to prevent or delay atherosclerosis progression, we analyzed effects of the Wnt/beta-catenin signaling pathway on monocyte adhesion to various human endothelial cells. Adhesion of fluorescein-labeled monocytes to various human endothelial cells was analyzed under a fluorescent microscope. Unlike sodium chloride, lithium chloride enhanced monocyte adhesion to endothelial cells in a dose-dependent manner. We further demonstrated that inhibitors for glycogen synthase kinase (GSK)-3beta or proteosome enhanced monocyte-endothelial cell adhesion. Results of semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) indicated that activation of Wnt/beta-catenin pathway did not change expression levels of mRNA for adhesion molecules. In conclusion, the canonical Wnt/beta-catenin pathway enhanced monocyte-endothelial cell adhesion without changing expression levels of adhesion molecules.

Carotenoids enhance phosphorylation of Akt and suppress tissue factor activity in human endothelial cells.

Enhanced production of tissue factor has been linked to development of cardiovascular disease due to endothelial activation, resulting in thrombosis of blood vessels. Epidemiological studies reported that diet-derived antioxidants might suppress and/or delay progression of cardiovascular disease. Detailed molecular level studies are needed to understand this effect with prevention as a goal. Water-dispersible forms of various carotenoids (beta-carotene, lutein and lycopene) from natural sources in microemulsion were used to study effects of carotenoids on tissue factor activity in human endothelial cells. All carotenoids studied suppressed tissue factor activity (P<.01) and gene expression in human endothelial cells. Our study also demonstrated that addition of Akt-specific inhibitor reversed the inhibitory effect of carotenoids on tissue factor activity, indicating that carotenoids enhanced phosphorylation of Akt and suppressed tissue factor activity in endothelial cells by this mechanism.

Compression and free expansion of single DNA molecules in nanochannels.

We investigated compression and ensuing expansion of long DNA molecules confined in nanochannels. Transverse confinement of DNA molecules in the nanofluidic channels leads to elongation of their unconstrained equilibrium configuration. The extended molecules were compressed by electrophoretically driving them into porelike constrictions inside the nanochannels. When the electric field was turned off, the DNA strands expanded. This expansion, the dynamics of which has not previously been observable in artificial systems, is explained by a model that is a variation of de Gennes's polymer model.

Human epicardial adipose tissue is a source of inflammatory mediators.

BACKGROUND: Inflammatory mediators that originate in vascular and extravascular tissues promote coronary lesion formation. Adipose tissue may function as an endocrine organ that contributes to an inflammatory burden in patients at risk of cardiovascular complications. In this study, we sought to compare expression of inflammatory mediators in epicardial and subcutaneous adipose stores in patients with critical CAD. METHODS AND RESULTS: Paired samples of epicardial and subcutaneous adipose tissues were harvested at the outset of elective CABG surgery (n=42; age 65+/-10 years). Local expression of chemokine (monocyte chemotactic protein [MCP]-1) and inflammatory cytokines (interleukin [IL]-1beta, IL-6, and tumor necrosis factor [TNF]-alpha) was analyzed by TaqMan real-time reverse transcription-polymerase chain reaction (mRNA) and by ELISA (protein release over 3 hours). Significantly higher levels of IL-1beta, IL-6, MCP-1, and TNF-alpha mRNA and protein were observed in epicardial adipose stores. Proinflammatory properties of epicardial adipose tissue were noted irrespective of clinical variables (diabetes, body mass index, and chronic use of statins or ACE inhibitors/angiotensin II receptor blockers) or plasma concentrations of circulating biomarkers. In a subset of samples (n=11), global gene expression was explored by DNA microarray hybridization and confirmed the presence of a broad inflammatory reaction in epicardial adipose tissue in patients with coronary artery disease. The above findings were paralleled by the presence of inflammatory cell infiltrates in epicardial adipose stores. CONCLUSIONS: Epicardial adipose tissue is a source of several inflammatory mediators in high-risk cardiac patients. Plasma inflammatory biomarkers may not adequately reflect local tissue inflammation. Current therapies do not appear to eliminate local inflammatory signals in epicardial adipose tissue.

Survival in Infarct Related Intramyocardial Dissection Importance of Early Echocardiography and Prompt Surgery.

Infarct related intramyocardial dissection, an unusual mechanical complication associated with recent inferior/inferoposterior myocardial infarction, is characterized by a septal defect and a dissection tract that originates on the left side of the interventricular septum, extends beyond the septum into the right ventricular free wall, and subsequently re-enters the right ventricle. The utility of echocardiography for diagnosis has been described. Despite aggressive therapy, the prognosis of intramyocardial dissection is reported to be dismal. We describe the use of prompt echocardiography in two patients, which established the diagnosis of infarct related intramyocardial dissection allowing early definitive surgery and long-term survival.