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1.
Acta Anaesthesiol Scand ; 66(3): 326-336, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34870851

ABSTRACT

BACKGROUND: Perioperative dysglycaemias are a risk for harm but guidelines to improve glucose management are poorly adhered to. AIM: To determine whether a specialized team and diabetes education improves the implementation of guidelines and glucose values. METHODS: We conducted a prospective study of 611 nonselected, consecutive patients attending for elective hip or knee arthroplasty. The first 209 patients received conventional care and the following 402 patients received intervention (Acute Glucose Service, AGS) in two chronological groups; either perioperatively (AGS1) or also preoperatively (AGS2). The AGS-team provided diabetes education, identified the patients with diabetes risk and adjusted the medication when needed. Capillary plasma glucose (CPG) was repeatedly measured and glycated haemoglobin (HbA1c) obtained before and after the surgery. The study objectives were to evaluate the staff actions when hyperglycaemia was severe (CPG >10 mmol/L), and to assess improvement of the glycaemic values and the complication rate within 3 months. RESULTS: None of the severely hyperglycaemic events in the reference group were treated according to guidelines. In the AGS 1 group, 50% and in the AGS2 group, 53% were appropriately managed (p < .001). The events of hyperglycaemia (CPG >7.8 mmol/L at least twice) and of severe hyperglycaemia (CPG >10 mmol/L) decreased in all patient groups. The medians of the highest, mean and variability of CPG values improved. The mean HbA1c improved significantly within AGS 2. There was no association between improved glycaemic care and early complications. CONCLUSIONS: AGS intervention significantly improves adherence to guidelines and glucose values.


Subject(s)
Blood Glucose , Glucose , Glycated Hemoglobin/analysis , Hospitals , Humans , Hypoglycemic Agents , Prospective Studies
3.
Acta Anaesthesiol Scand ; 64(9): 1253-1261, 2020 10.
Article in English | MEDLINE | ID: mdl-32615649

ABSTRACT

BACKGROUND: Perioperative dysglycaemia is associated with deleterious outcomes but guidelines to improve glucose management are poorly or inconsistently adhered to. We evaluated glucose management among diabetic and non-diabetic patients undergoing elective hip or knee arthroplasty. METHODS: Capillary plasma glucose (CPG) was measured prospectively four times daily of 209 patients undergoing elective hip or knee surgery. Actions of the attending teams to CPG values and detection of patients at risk were analysed. RESULTS: A total of 209 patients were enrolled. All diabetic patients on insulin (6/6) had hyperglycaemia (≥7.8 mmol/l) more than twice and severe hyperglycaemia (>10 mmol/l) at least once. Of the 27 diabetic patients not on insulin 26 (96.3%) had CPG ≥ 7.8 mmol/l ≥ 2 times and 17 (63%) >10 mmol/l. The corresponding figures of the 176 non-diabetic patients were 137 (77.8%) and 61 (34.7%). Severe hyperglycaemia occurred in 54/176 (30.1%) of the non-diabetic patients with pre-operative HbA1c < 42 mmol/mol and random plasma glucose < 7.8 mmol/l. Of the 84 hyperglycaemic episodes > 10 mmol/l, none was treated. Patients with a FINDRISC score ≥ 12 (corresponding to moderate to high risk of diabetes) and hyperglycaemia went unnoticed. CONCLUSIONS: Hyperglycaemia is common among elective orthopaedic surgery patients with or without diabetes. More than 80% of the 209 patients had hyperglycaemia and 40% had severe hyperglycaemia. None of the patients was treated according to guidelines and none of the patients at risk of hyperglycaemia or diabetes was noticed. There is an obvious need for further education and support by diabetes specialists. CLINICAL TRIAL REGISTRATION: Clinical trials, gov. NCT03306810.


Subject(s)
Diabetes Mellitus , Hyperglycemia , Arthroplasty , Blood Glucose , Diabetes Mellitus/epidemiology , Glycated Hemoglobin/analysis , Humans
4.
Circulation ; 140(8): 627-640, 2019 08 20.
Article in English | MEDLINE | ID: mdl-31352795

ABSTRACT

BACKGROUND: Ischemia-reperfusion injury may compromise the short-term and long-term prognosis after heart transplantation. Experimental studies show that simvastatin administered to the organ donor is vasculoprotective and inhibits cardiac allograft ischemia-reperfusion injury. METHODS: Eighty-four multiorgan donors were randomly assigned to receive 80 mg of simvastatin (42 donors) via nasogastric tube after declaration of brain death and upon acceptance as a cardiac donor, or to receive no simvastatin (42 donors). The primary efficacy end point was postoperative plasma troponin T and I levels during the first 24 hours after heart transplantation. Secondary end points included postoperative hemodynamics, inflammation, allograft function, rejections and rejection treatments, and mortality. Results: Organ donor simvastatin treatment significantly reduced the heart recipient plasma levels of troponin T by 34% (14 900 ± 12 100 ng/L to 9800 ± 7900 ng/L, P=0.047), and troponin I by 40% (171 000 ± 151 000 ng/L to 103 000 ± 109 000 ng/L, P=0.023) at 6 hours after reperfusion, the levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) by 36% (32 800 ± 24 300 ng/L to 20 900 ± 15 900 ng/L; P=0.011) at 1 week, and the number of rejection treatments with hemodynamic compromise by 53% within the first 30 days (P=0.046). Donor simvastatin treatment did not affect donor lipid levels but was associated with a specific transplant myocardial biopsy gene expression profile, and a decrease in recipient postoperative plasma levels of CXCL10 (C-X-C motif chemokine 10), interleukin-1α, placental growth factor, and platelet-derived growth factor-BB. Postoperative hemodynamics, biopsy-proven acute rejections, and mortality were similar. No adverse effects were seen in recipients receiving noncardiac solid organ transplants from simvastatin-treated donors. CONCLUSIONS: Donor simvastatin treatment reduces biomarkers of myocardial injury after heart transplantation, and-also considering its documented general safety profile-may be used as a novel, safe, and inexpensive adjunct therapy in multiorgan donation. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01160978.


Subject(s)
Allografts/drug effects , Graft Rejection/drug therapy , Heart Transplantation , Inflammation/drug therapy , Reperfusion Injury/drug therapy , Simvastatin/therapeutic use , Adolescent , Adult , Aged , Chemokine CXCL10/blood , Double-Blind Method , Female , Graft Rejection/mortality , Hemodynamics/drug effects , Humans , Male , Middle Aged , Reperfusion Injury/mortality , Tissue Donors , Transplantation, Homologous , Troponin T/blood , Young Adult
5.
Perfusion ; 34(8): 705-713, 2019 11.
Article in English | MEDLINE | ID: mdl-31090485

ABSTRACT

INTRODUCTION: A minimal volume ventilation method for robotically assisted mitral valve surgery is described in this study. In an attempt to reduce postoperative pulmonary dysfunction, 40 of 174 patients undergoing robotically assisted mitral valve surgery were ventilated with a small tidal volume during cardiopulmonary bypass. METHODS: After propensity score matching, 31 patients with minimal volume ventilation were compared with 54 patients with no ventilation. Total ventilation time, PaO2/FiO2 ratio, arterial lactate concentration, and the rate of unilateral pulmonary edema in the matched minimal ventilation and standard treatment groups were evaluated. RESULTS: Patients in the minimal ventilation group had shorter ventilation times, 12.0 (interquartile range: 9.9-15.0) versus 14.0 (interquartile range: 12.0-16.3) hours (p = 0.036), and lower postoperative arterial lactate levels, 0.99 (interquartile range: 0.81-1.39) versus 1.28 (interquartile range: 0.99-1.86) mmol/L (p = 0.01), in comparison to patients in the standard treatment group. There was no difference in postoperative PaO2/FiO2 ratio levels or in the rate of unilateral pulmonary edema between the groups. CONCLUSION: Minimal ventilation appeared beneficial in terms of total ventilation time and blood lactatemia, while there was no improvement in arterial blood gas measurements or in the rate of unilateral pulmonary edema. The lower postoperative arterial lactate levels may suggest improved lung perfusion among patients in the minimal volume ventilation group. The differences in the ventilation times were in fact small, and further studies are required to confirm the possible advantages of the minimal volume ventilation method in robotically assisted cardiac surgery.


Subject(s)
Cardiopulmonary Bypass/methods , Mitral Valve/surgery , Robotic Surgical Procedures/methods , Adult , Cardiopulmonary Bypass/adverse effects , Female , Heart Valve Diseases/blood , Heart Valve Diseases/surgery , Humans , Lactic Acid/blood , Male , Middle Aged , Pulmonary Edema/blood , Pulmonary Edema/etiology , Pulmonary Ventilation , Robotic Surgical Procedures/adverse effects
6.
Eur J Cardiothorac Surg ; 55(4): 780-787, 2019 Apr 01.
Article in English | MEDLINE | ID: mdl-30534984

ABSTRACT

OBJECTIVES: Our goal was to study the outcome of patients with cardiogenic shock who were treated with venoarterial extracorporeal membrane oxygenation (VA ECMO), including the subsequent long-term health-related quality of life (HRQoL). METHODS: We conducted a retrospective study of 133 consecutive patients treated in a single centre from 2007 to 2016. The HRQoL was studied using the EuroQuol-5 dimensions-3 level questionnaire and the RAND 36-Item Short Form Health Survey at a minimum of 1 year after VA ECMO. RESULTS: Of all patients, 66 (49.6%) were weaned from VA ECMO and 16 (12.0%) patients were bridged directly to a transplant, 15 (11.3%) to a ventricular assist device and 1 (0.8%) to a total artificial heart. Survival to discharge was 63.9% and to 1 year, 60.9%. A higher in-hospital mortality rate was independently associated with lower HCO3 at VA ECMO implantation [odds ratio (OR) 1.2/decrease of 1 mmol/l in HCO3 (95% confidence interval 1.1-1.3, P < 0.001)] and with increased need of red blood cells transfused during intensive care [OR 1.9/unit of red blood cells needed/day (95% confidence interval 1.4-2.6, P < 0.001)]. HRQoL measured with the EuroQuol-5 dimensions-3 level questionnaire was equal to the HRQoL of the general population. In the 36-Item Short Form questionnaire, patients reported better emotional well-being and equal energy, pain and general health perception compared to the general population. Limitations were experienced only in physical health. In total, 56% of the patients ≤ 60 years had returned to work. CONCLUSIONS: VA ECMO can provide acceptable long-term survival with good HRQoL for selected patients with refractory cardiogenic shock. Timing of patient assessment and of VA ECMO implantation is essential because deeper acidosis is associated with a higher in-hospital mortality rate.


Subject(s)
Extracorporeal Membrane Oxygenation , Quality of Life , Shock, Cardiogenic/therapy , Extracorporeal Membrane Oxygenation/mortality , Female , Humans , Male , Middle Aged , Retrospective Studies , Shock, Cardiogenic/mortality , Surveys and Questionnaires , Survival Analysis
7.
Transpl Infect Dis ; 20(3): e12868, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29512249

ABSTRACT

BACKGROUND: Cytomegalovirus (CMV) remains an important pathogen in solid organ transplant patients. OBJECTIVE: We executed a hybrid prophylactic and pre-emptive valganciclovir (VGCV) prophylaxis to prevent CMV infection in heart transplant patients with anti-thymocyte globulin (ATG) induction and retrospectively evaluated the efficacy and safety of this regimen. METHODS: Hundred adult heart transplant patients between 2004 and 2010 were included. Recipients with CMV serostatus D+/R- received VGCV 900 mg OD for 6 months and 94.2% (81/86) of R+ recipients received a low-dose 450 mg OD for 3 months. Blood CMV was monitored until 3 months after cessation of the prophylaxis. RESULTS: All patients accomplished the prophylaxis. The overall incidence of CMV disease was 4% (4/100) and it was more frequent in D+/R- patients (P = .001). Three of eighty-six (3.5%) of R+ patients had CMV infection (one CMV disease) while on prophylaxis, 2/3 were still on the original significantly reduced renal dose though. There was one late CMV disease in both D+/R- and R+ groups. Ganciclovir/VGCV treatment was successful in all patients. CONCLUSIONS: The hybrid strategy with low-dose VGCV in R+ patients with ATG was efficient and safe. The good treatment results indicate that the regimen did not lead to a clinically relevant resistance. Optimal renal dosage is essential throughout prophylaxis.


Subject(s)
Antilymphocyte Serum/therapeutic use , Antiviral Agents/administration & dosage , Cytomegalovirus Infections/prevention & control , Ganciclovir/analogs & derivatives , Heart Transplantation/adverse effects , Adult , Aged , Cytomegalovirus/drug effects , Cytomegalovirus/immunology , Cytomegalovirus Infections/virology , Female , Ganciclovir/administration & dosage , Ganciclovir/adverse effects , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/therapeutic use , Incidence , Male , Medical Records , Middle Aged , Pre-Exposure Prophylaxis , Retrospective Studies , Treatment Outcome , Valganciclovir , Young Adult
8.
J Thorac Cardiovasc Surg ; 155(4): 1463-1471, 2018 04.
Article in English | MEDLINE | ID: mdl-29221742

ABSTRACT

OBJECTIVE: To report the learning curve and early results of robotic mitral valve repairs in comparison with propensity score-matched sternotomy controls after the adoption of a robotic mitral valve surgery program in a university teaching hospital. METHODS: A total of 142 patients underwent robotic mitral valve repair due to degenerative mitral regurgitation between May 2011 and December 2015. Control patients operated on via the conventional sternotomy approach were selected by the use of propensity score analysis resulting in 2 well-matched study groups. RESULTS: Valve repair rate was 98.6% and 97.9% in the robotic and sternotomy groups, respectively. Operation length, cardiopulmonary bypass, aortic crossclamp, and ventilation times were shorter in the sternotomy group. All of these times were statistically significantly reduced within the robotic group during the learning curve. Even though there was no statistically significant difference in the rate of perioperative complications between the groups, 3 patients in the robotic group required postoperative extracorporeal membrane oxygenation due to low cardiac output, and 1 patient in the robotic group died. In the robotic and sternotomy groups, 86.3% versus 84.7% of patients had grade ≤1+ mitral valve regurgitation at the latest follow-up visit, and there was no statistically significant difference in survival or reoperation rate between the 2 study groups during follow-up. CONCLUSIONS: The present series reports the entire early learning curve related to the introduction of robotic mitral valve repair in our institution. In all, repair rate and early durability were acceptable, but more patients in the robotic group had serious complications. Early major robotic complications that occurred may have been related to the simultaneous use of intra-aortic occlusion.


Subject(s)
Cardiac Surgical Procedures , Mitral Valve Insufficiency , Robotic Surgical Procedures , Humans , Mitral Valve , Retrospective Studies
9.
Adv Wound Care (New Rochelle) ; 5(5): 198-207, 2016 May 01.
Article in English | MEDLINE | ID: mdl-27134764

ABSTRACT

Significance: The treatment of chronic wounds results in an enormous drain on healthcare resources in terms of workload, costs, frustration, and impaired quality of life, and it presents a clinical challenge for physicians worldwide. Effective local treatment of a chronic wound has an important role, particularly in patients who are-because of their poor general condition, diminished life expectancy, or unacceptable operative risk-outside of surgical treatment. Recent Advances: Since 2002, our multidisciplinary research group has investigated the properties of Norway spruce (Picea abies) resin in wound healing and its therapeutic applications in wound care. Resin is a complex mixture of resin acids (e.g., abietic, neoabietic, dehydroabietic, pimaric, isopimaric, levopimaric, sandrakopimaric, and palustric acids) and lignans (e.g., pino-, larici-, matairesinol, and p-hydroxycinnamic acid) having substantial antimicrobial, wound-healing, and skin regeneration enhancing properties. Critical Issues: The cornerstone in successful wound care is an efficient causal treatment of the underlying co-morbidities, for example, diabetes, malnutrition, vascular- or certain systemic diseases. However, definitive diagnosis and specific therapy of a chronic wound is often difficult, because the etiology is practically always multi-factorial, and in the chronic phase, confounding factors such as infections invariably impede wound healing. Future Directions: To study the exact molecular mechanism of actions by which resin promotes cellular regeneration and epithelialization during the wound-healing process. To investigate potential antimicrobial properties of resin against the most ominous multidrug-resistant beta-lactamase (including carbapenemases and metallo-ß-lactamases) producing bacteria, and to individualize those pharmacologically active compounds which are responsible for the antimicrobial activity of resin.

10.
Interact Cardiovasc Thorac Surg ; 23(1): 133-41, 2016 07.
Article in English | MEDLINE | ID: mdl-26984965

ABSTRACT

OBJECTIVES: Plasma troponins, measured by fourth-generation assays, are associated with increased mortality and morbidity after cardiac surgery. They also offer predictive information in addition to EuroSCORE, a widely used risk model after cardiac surgery. However, preoperatively measured troponin has provided no additional information to postoperative values. Whether these facts hold true also for the high-sensitivity fifth-generation troponin assay and the better calibrated risk model, EuroSCORE II, is unknown. We hypothesized that preoperative and/or postoperative high-sensitivity troponin T (hs-TnT) would increase the predictive value of EuroSCORE II. METHODS: Consecutive coronary artery bypass grafting (CABG) and other cardiac surgical patients were prospectively enrolled in a university hospital. Plasma samples and EuroSCORE II variables were collected. The primary and secondary end-points were 180-day mortality and any major adverse event within 30 days, and 961-day mortality. The data were analysed by Kaplan-Meier survival curves, regression analyses, receiver operator characteristic curves and decision curve analysis. RESULTS: Mortality rates in 180 days were 3.5% (15/428) in CABG and 6.4% (14/220) in other cardiac surgical patients. Survival curves differed only in patients with not only high postoperative hs-TnT value (>500 ng/l), but also high preoperative hs-TnT value (>14 ng/l), compared with patients with both hs-TnT values low. Adding hs-TnT to EuroSCORE II improved the prediction of 180-day mortality in other cardiac surgical patients (maximum net benefit of 1.5%), but not in CABG patients. Regarding major adverse events, adding hs-TnT to EuroSCORE II improved the prediction in both CABG patients and other cardiac surgical patients (maximum net benefits of 3 and 7%). CONCLUSIONS: Elevated postoperative hs-TnT was predictive of mortality only when combined with elevated preoperative hs-TnT. Hs-TnT measurements added information to the EuroSCORE II regarding major adverse events in all cardiac surgical patients and regarding 180-day mortality in non-CABG patients.


Subject(s)
Cardiac Surgical Procedures/adverse effects , Cardiovascular Diseases/blood , Cardiovascular Diseases/surgery , Postoperative Complications/blood , Troponin T/blood , Aged , Biomarkers/blood , Cardiovascular Diseases/mortality , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Morbidity , Postoperative Complications/etiology , Postoperative Complications/mortality , Predictive Value of Tests , Prognosis , Prospective Studies , ROC Curve , Severity of Illness Index
11.
Transplantation ; 100(2): 303-13, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26371596

ABSTRACT

BACKGROUND: Microvascular dysfunction and cardiomyocyte injury are hallmarks of ischemia-reperfusion injury (IRI) after heart transplantation. Platelet-derived growth factors (PDGF) have an ambiguous role in this deleterious cascade. On one hand, PDGF may exert vascular stabilizing and antiapoptotic actions through endothelial-pericyte and endothelial-cardiomyocyte crosstalk in the heart; and on the other hand, PDGF signaling mediates neointimal formation and exacerbates chronic rejection in cardiac allografts. The balance between these potentially harmful and beneficial actions determines the final outcome of cardiac allografts. METHODS AND RESULTS: We transplanted cardiac allografts from Dark Agouti rat and Balb mouse donors to fully major histocompatibility complex-mismatched Wistar Furth rat or C57 mouse recipients with a clinically relevant 2-hour cold ischemia and 1-hour warm ischemia. Ex vivo intracoronary delivery of adenovirus-mediated gene transfer of recombinant human PDGF-BB upregulated messenger RNA expression of anti-mesenchymal transition and survival factors BMP-7 and Bcl-2 and preserved capillary density in rat cardiac allografts at day 10. In mouse cardiac allografts PDGF receptor-ß, but not -α intragraft messenger RNA levels were reduced and capillary protein localization was lost during IRI. The PDGF receptor tyrosine kinase inhibitor imatinib mesylate and a monoclonal antibody against PDGF receptor-α enhanced myocardial damage evidenced by serum cardiac troponin T release in the rat and mouse cardiac allografts 6 hours after reperfusion, respectively. Moreover, imatinib mesylate enhanced rat cardiac allograft vasculopathy, cardiac fibrosis, and late allograft loss at day 56. CONCLUSIONS: Our results suggest that PDGF-B signaling may play a role in endothelial and cardiomyocyte recovery from IRI after heart transplantation.


Subject(s)
Genetic Therapy/methods , Heart Transplantation/adverse effects , Myocardial Reperfusion Injury/prevention & control , Myocytes, Cardiac/metabolism , Proto-Oncogene Proteins c-sis/biosynthesis , Adenoviridae/genetics , Allografts , Animals , Becaplermin , Bone Morphogenetic Protein 7/genetics , Bone Morphogenetic Protein 7/metabolism , Disease Models, Animal , Endothelial Cells/metabolism , Genetic Vectors , Imatinib Mesylate/pharmacology , Male , Mice, Inbred BALB C , Mice, Inbred C57BL , Myocardial Reperfusion Injury/genetics , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Myocytes, Cardiac/pathology , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Proto-Oncogene Proteins c-sis/genetics , Rats, Wistar , Receptors, Platelet-Derived Growth Factor/antagonists & inhibitors , Receptors, Platelet-Derived Growth Factor/genetics , Receptors, Platelet-Derived Growth Factor/metabolism , Time Factors
12.
ASAIO J ; 62(2): 139-42, 2016.
Article in English | MEDLINE | ID: mdl-26579977

ABSTRACT

The durability of CBAS Heparin Surface on EXCOR pumps retrieved after clinical use for varying periods of time was studied by analyzing samples for surface heparin density and bioactivity. The mean time of clinical use of the investigated 14 EXCOR pumps was 178 days (range, 15-461 days). Mean heparin density was 3.1 ± 0.6 µg/cm² (range, 2.2-4.8 µg/cm²), and the measured mean heparin bioactivity was 14 ± 5 ρmol/cm² (range: 7-27 ρmol/cm²). There was no detectable degradation or loss of function of CBAS Heparin Surface over time. Samples from the housing and the membrane of the EXCOR pump showed no significant difference in heparin bioactivity or density. The CBAS Heparin Surface stays on the surface and remains bioactive on the EXCOR pump at least up until 1 year. This is an important demonstration of coating durability and supports the mid-term and long-term clinical use as bridge-to-heart transplantation or to myocardial recovery.


Subject(s)
Drug Stability , Heart-Assist Devices , Heparin/analysis , Humans
13.
J Robot Surg ; 9(3): 235-41, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26531204

ABSTRACT

The aim of this study was to evaluate the clinical outcome after robotically assisted myxoma surgery performed at our institution. Altogether nine patients underwent robotically assisted atrial myxoma excision. A control group was selected from 18 consecutive patients who underwent an isolated atrial myxoma excision via conventional sternotomy. Preoperative patient characteristics were similar between the two study groups. Postoperative health-related quality of life (HRQoL) was also evaluated. All robotic operations were completed successfully using the da Vinci™ telesurgical system. There was no mortality in either of the two study groups. Procedure, cardiopulmonary bypass, aortic occlusion, and ventilation times were shorter in the sternotomy group when compared to the robotic group. Length of stay was statistically significantly shorter in the robotically assisted group. Postoperative quality of life did not differ between the two study groups. We conclude that robotically assisted surgery is a feasible method for treating atrial myxomas.


Subject(s)
Heart Atria/surgery , Heart Neoplasms/surgery , Myxoma/surgery , Quality of Life , Robotic Surgical Procedures/methods , Aged , Female , Humans , Male , Middle Aged , Postoperative Complications
15.
Transpl Int ; 26(11): 1126-37, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24102821

ABSTRACT

Heart transplant gene therapy requires vectors with long-lasting gene expression, high cardiotropism, and minimal pathological effects. Here, we examined transduction properties of ex vivo intracoronary delivery of adeno-associated virus (AAV) serotype 2, 8, and 9 in rat syngenic and allogenic heart transplants. Adult Dark Agouti (DA) rat hearts were intracoronarily perfused ex vivo with AAV2, AAV8, or AAV9 encoding firefly luciferase and transplanted heterotopically into the abdomen of syngenic DA or allogenic Wistar-Furth (WF) recipients. Serial in vivo bioluminescent imaging of syngraft and allograft recipients was performed for 6 months and 4 weeks, respectively. Grafts were removed for PCR-, RT-PCR, and luminometer analysis. In vivo bioluminescent imaging of recipients showed that AAV9 induced a prominent and stable luciferase activity in the abdomen, when compared with AAV2 and AAV8. However, ex vivo analyses revealed that intracoronary perfusion with AAV2 resulted in the highest heart transplant transduction levels in syngrafts and allografts. Ex vivo intracoronary delivery of AAV2 resulted in efficient transgene expression in heart transplants, whereas intracoronary AAV9 escapes into adjacent tissues. In terms of cardiac transduction, these results suggest AAV2 as a potential vector for gene therapy in preclinical heart transplants studies, and highlight the importance of delivery route in gene transfer studies.


Subject(s)
Dependovirus/genetics , Genetic Therapy/methods , Genetic Vectors , Heart Transplantation , Heart/virology , Animals , Dependovirus/classification , Isografts , Luciferases/genetics , Male , Myocardium/metabolism , Rats , Transgenes/genetics
16.
Ann Thorac Surg ; 95(2): 579-85, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23103004

ABSTRACT

BACKGROUND: Valve-sparing aortic root reconstruction (VSRR) is an accepted method to treat patients with aortic root dilation. The role of the VSRR is less well defined for patients with bicuspid aortic valve, severe aortic valve insufficiency, congenital heart defects, and type A aortic dissection. We studied the clinical outcome of patients who underwent VSRR for expanded indications. METHODS: Seventy-eight patients underwent VSRR between the 2005 and 2012. Seventy-two patients (92%) underwent reimplantation and 6 patients (8%) were operated on with the remodeling technique. The mean age was 51 ± 12 years (range 24 to 73). For 71 patients (91%), the operation was elective, and for 7 (9%; all with type A aortic dissection), on an emergency basis. Preoperatively, the degree of aortic insufficiency was graded as 2+ or greater for 27 patients (35%). Connective tissue disorder (Marfan or Loeys-Dietz), bicuspid aortic valve, or congenital heart disease was present in 15 (19%), 15 (19%), and 7 patients (9%), respectively. Concomitant aortic valve leaflet repair was performed for 39 patients (50%). The mean follow-up time was 2.4 ± 1.7 years (range, 0.1 to 7.0). RESULTS: Thirty-day mortality was zero. The rate of postoperative complications was low: stroke 3%, renal failure 3%, prosthesis infection 1%, and low cardiac output syndrome 1%. Survival was 100% at 1 year and 97% at 5 years. Freedom from recurrent aortic valve insufficiency (≥2+) during the follow-up was 94%. CONCLUSIONS: The midterm results of VSRR in terms of survival, freedom from recurrent aortic valve insufficiency, and the need for reoperation are excellent, even for high-risk patients.


Subject(s)
Aortic Aneurysm, Thoracic/surgery , Adult , Aged , Cardiac Surgical Procedures/methods , Feasibility Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Time Factors , Treatment Outcome , Vascular Surgical Procedures/methods , Young Adult
17.
Mycoses ; 56(3): 289-96, 2013 May.
Article in English | MEDLINE | ID: mdl-23131104

ABSTRACT

In in vitro tests, natural coniferous resin from the Norway spruce (Picea abies) is strongly antifungal. In this observational study, we tested the clinical effectiveness of a lacquer composed of spruce resin for topical treatment of onychomycosis. Thirty-seven patients with clinical diagnosis of onychomycosis were enrolled into the study. All patients used topical resin lacquer treatment daily for 9 months. A mycological culture and potassium hydroxide (KOH) stain were done from nail samples in the beginning and in the end of the study. Treatment was considered effective, if a mycological culture was negative and there was an apparent clinical cure. At study entry, 20 patients (20/37; 54%; 95% CI: 38-70) had a positive mycological culture and/or positive KOH stain for dermatophytes. At study end, the result of 13 patients was negative (13/19; 68%; 95% CI: 48-89). In one case (1/14; 7%; 95% CI: 0-21) the mycological culture was initially negative, but it turned positive during the study period. By 14 compliant patients (14/32; 44%; 95% CI: 27-61), resin lacquer treatment was considered clinically effective: complete healing took place in three cases (9%) and partial healing in 11 cases (85%). The results indicate some evidence of clinical efficacy of the natural coniferous resin used for topical treatment of onychomycosis.


Subject(s)
Antifungal Agents/therapeutic use , Nails/microbiology , Onychomycosis/drug therapy , Picea/chemistry , Resins, Plant/therapeutic use , Trichophyton/isolation & purification , Adult , Aged , Aged, 80 and over , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Female , Humans , Hydroxides/chemistry , Male , Middle Aged , Onychomycosis/pathology , Potassium Compounds/chemistry , Prospective Studies , Resins, Plant/chemistry , Severity of Illness Index , Time Factors , Treatment Outcome
18.
Am J Pathol ; 181(5): 1607-20, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22959907

ABSTRACT

Chronic inflammation, a hallmark of obliterative bronchiolitis, is known to induce lymphangiogenesis. We therefore studied the role of lymphangiogenic vascular endothelial growth factor C (VEGF-C), its receptor VEGFR-3, and lymphangiogenesis during development of experimental obliterative bronchiolitis [ie, obliterative airway disease (OAD)] in rat tracheal allografts. The functional importance of VEGF-C was investigated by adenovirus-mediated overexpression of VEGF-C (AdVEGF-C), and by inhibition of VEGF-C activity with VEGFR-3-Ig (AdVEGFR-3-Ig). Analyses included histology, immunohistochemistry, and real-time RT-PCR 10 and 30 days after transplantation. In the course of OAD development, lymphangiogenesis was induced in the airway wall during the alloimmune response, which was reversed by cyclosporine A in a dose-dependent fashion. VEGF-C overexpression in tracheal allografts induced epithelial activation, neutrophil chemotaxis, and a shift toward a Th17 adaptive immune response, followed by enhanced lymphangiogenesis and the development of OAD. In contrast, inhibition of VEGF-C activity with VEGFR-3-Ig inhibited lymphangiogenesis and angiogenesis and reduced infiltration of CD4(+) T cells and the development of OAD. Lymphangiogenesis was linked to T-cell responses during the development of OAD, and VEGF-C/VEGFR-3 signaling modulated innate and adaptive immune responses in the development of OAD in rat tracheal allografts. Our results thus suggest VEGFR-3-signaling as a novel strategy to regulate T-cell responses in the development of obliterative bronchiolitis after lung transplantation.


Subject(s)
Adaptive Immunity/immunology , Bronchiolitis Obliterans/immunology , Bronchiolitis Obliterans/metabolism , Immunity, Innate/immunology , Signal Transduction/immunology , Vascular Endothelial Growth Factor C/metabolism , Vascular Endothelial Growth Factor Receptor-3/metabolism , Adaptive Immunity/drug effects , Animals , Bronchiolitis Obliterans/pathology , Bronchiolitis Obliterans/physiopathology , Chemotaxis/drug effects , Cyclosporine/pharmacology , Dendritic Cells/drug effects , Dendritic Cells/immunology , Dose-Response Relationship, Drug , Down-Regulation/drug effects , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Epithelial Cells/pathology , Epithelium/drug effects , Epithelium/metabolism , Epithelium/pathology , Graft Rejection/complications , Graft Rejection/immunology , Graft Rejection/pathology , Graft Rejection/physiopathology , Immunity, Innate/drug effects , Immunoglobulins/pharmacology , Inflammation/complications , Inflammation/immunology , Inflammation/pathology , Lymphangiogenesis/drug effects , Macrophages/drug effects , Macrophages/immunology , Neutrophils/drug effects , Rats , Signal Transduction/drug effects , Th17 Cells/drug effects , Th17 Cells/immunology , Trachea/drug effects , Trachea/pathology , Trachea/transplantation , Transplantation, Homologous , Up-Regulation/drug effects , Vascular Endothelial Growth Factor C/antagonists & inhibitors
19.
Int J Dermatol ; 51(6): 726-32, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22607295

ABSTRACT

Resin is a natural product of coniferous trees. Salves manufactured from spruce resin (Picea abies) have been used for centuries to treat wounds and skin infections. We report a pilot clinical trial designed to investigate healing rates, factors that contribute to delayed wound healing, cost-effectiveness, and incidence of allergic reactions when resin salve is used to treat complicated surgical wounds. The trial involved 23 patients in whom wound healing after surgery was delayed. These patients were assigned to resin salve treatment. The primary outcome measure was the number of days to complete wound healing. Secondary objectives included an assessment of factors contributing to delayed wound healing, an estimation of associated costs, and an investigation into the occurrence of allergic reactions related to resin salve therapy. The study achieved a healing rate of 100%. The mean ± SD healing time was 43 ± 24 days. The mean ± SD wound size (length × width × depth) was (29 ± 19) × (12 ± 7) × (4 ± 3) mm. Wound size, use of corticosteroids or other immunosuppressants, and immobilization were statistically significant (P < 0.05) contributors to delayed wound healing and impaired re-epithelialization. The total mean ± SD costs of the resin salve treatment were €45.0 ± 26.0 per patient during the entire treatment period and €1.2 ± 0.5 per treatment day. The rate of allergic reactions was 0%. The results of this pilot trial indicate that complicated surgical wounds may be treated successfully with resin salve. The treatment method is clinically effective and cost-effective, and the rate of allergic reactions is low.


Subject(s)
Phytotherapy , Picea , Postoperative Complications , Resins, Plant/therapeutic use , Wound Healing/drug effects , Adolescent , Adrenal Cortex Hormones/adverse effects , Adult , Aged , Aged, 80 and over , Female , Humans , Immobilization/adverse effects , Immunosuppressive Agents/adverse effects , Male , Middle Aged , Multivariate Analysis , Ointments , Phytotherapy/economics , Pilot Projects , Young Adult
20.
Duodecim ; 127(19): 2045-53, 2011.
Article in Finnish | MEDLINE | ID: mdl-22073536

ABSTRACT

In severe, acute or chronic heart failure, the heart and the circulation can be mechanically supported, if the patient's life is in danger despite maximal drug therapy, and other cardiologic or heart surgery treatment options or a suitable heart transplant are not available. Long-term prognosis of those treated with mechanical support has improved in the 2000's. This is based on technically advanced equipment, improved treatment practices, properly targeted patient selection and more accurate timing of therapy.


Subject(s)
Heart Failure/therapy , Heart-Assist Devices , Adult , Humans , Patient Selection , Prognosis
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