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1.
J Am Coll Surg ; 236(6): 1155, 2023 06 01.
Article in English | MEDLINE | ID: mdl-36927818
2.
J Am Coll Surg ; 234(6): 1064-1072, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35703798

ABSTRACT

BACKGROUND: Exploring the lived experiences of surgeons is necessary to understand the changing culture of surgery and the unique challenges of being a woman in surgery. Surgeons have significant experiences and observations best discovered through qualitative study. The purpose of this study is to identify the similarities and differences between the experiences of men and women surgeons after initiation of mandatory microaggression training. STUDY DESIGN: Qualitative semi-structured interviews with female and male surgeons and residents were done following a year-long series of training sessions on the detrimental effects of microaggression. Participants were selected using a convenience sampling method. MAXQDA coding software (Verbi) was used to evaluate interview transcripts with thematic analysis. RESULTS: Nineteen surgeons and surgical residents were interviewed. The participants were of equal gender identification, with the majority being attending surgeons. Multiple themes highlighted similarities and differences between male and female participants. Differences were noted in identification of a sensitive personality, family planning considerations, and experiences of bias. Similarities were related to the personality traits required to be successful in surgery, the sacrifice inherent to a surgical career, and the war rhetoric used to describe the comradery of residency. CONCLUSION: The challenges and rewards of surgery are similar for women and men, but women have additional stressors, including gender-based bias, microaggression, and family planning. These stressors take up energy, decreasing the mental space available for additional roles and affecting the work environment. Microaggression education can incite necessary discussions of bias and provide women with an opportunity to reflect on and share their experiences.


Subject(s)
Internship and Residency , Physicians, Women , Surgeons , Female , Humans , Male , Qualitative Research , Sexism
3.
J Am Coll Surg ; 235(3): 510-518, 2022 09 01.
Article in English | MEDLINE | ID: mdl-35588528

ABSTRACT

BACKGROUND: Surgical culture has shifted to recognize the importance of resident well-being. This is the first study to longitudinally track regional surgical resident well-being over 5 years. STUDY DESIGN: An anonymous cross-sectional, multi-institutional survey of New England general surgery residents using novel and published instruments to create three domains: health maintenance, burnout, and work environment. RESULTS: Overall, 75% (15 of 20) of programs participated. The response rate was 44% (250 of 570), and 53% (133 of 250) were women, 94% (234 of 250) were 25 to 34 years old, and 71% (178 of 250) were in a relationship. For health maintenance, 57% (143 of 250) reported having a primary care provider, 26% (64 of 250) had not seen a primary care provider in 2 years, and 59% (147 of 250) endorsed being up to date with age-appropriate health screening, but only 44% (109 of 250) were found to actually be up to date. Only 14% (35 of 250) reported exercising more than 150 minutes/week. The burnout rate was 19% (47 of 250), with 32% (81 of 250) and 25% (63 of 250) reporting high levels of emotional exhaustion and depersonalization, respectively. For program directors and attendings, 90% of residents reported that they cared about resident well-being. Eighty-seven percent of residents believed that it was acceptable to take time off during the workday for a personal appointment, but only 49% reported that they would personally take the time. CONCLUSIONS: The personal health maintenance of general surgery residents has changed little over the past five years, despite an overwhelming majority of residents reporting that attendings and program directors care about their well-being. Further study is needed to understand the barriers to improvement of resident wellbeing.


Subject(s)
Burnout, Professional , Internship and Residency , Adult , Burnout, Professional/epidemiology , Burnout, Professional/psychology , Cross-Sectional Studies , Female , Humans , Male , New England , Surveys and Questionnaires
4.
J Surg Educ ; 78(2): 400-404, 2021.
Article in English | MEDLINE | ID: mdl-32771279

ABSTRACT

OBJECTIVE: The interview process for applying to general surgery residency is burdened by a high volume of applicants, resulting in unprofessional behavior by both applicants and programs. Sharing more information regarding interview scheduling with applicants may limit fourth year medical student educational disruptions, minimized late cancellations to interview, and improve overall satisfaction with the process. Thus, we set out to determine what information is currently available to applicants. DESIGN: We used publicly accessible sources to determine what information was shared by US general surgery residency programs with applicants. Specifically, we looked at the deadline for applications, United States Medical Licensing Examination Step 1 and 2 score cutoffs, number of interview dates available, specific interview dates, a stated policy to not offering more interviews than slots, dates when applicants can expect to be notified of interview offers, notification of decision to decline, and International Medical Graduate and visa policies. SETTING: This study took place at Maine Medical Center in Portland, Maine, an academic medical center with a general surgery residency program. PARTICIPANTS: Not applicable. RESULTS: Three hundred seventeen programs were examined. Seventy-six percent of programs specified an application deadline, 65% of programs specified a Step 1 cut-off score, 50% of programs specified a Step 2 cut-off score, 61% of programs stated a visa policy, and 50% of programs stated an International Medical Graduate policy. Twenty-five percent of programs disclosed the number of interview dates, 23% disclosed what those interview dates were. About 3.4% of programs gave interview release dates, 2.8% of programs notify applicants of decline to interview, and 0.63% of programs explicitly describe a policy of offering only as many interviews as slots available. Thirty-two percent of programs provided conflicting information. CONCLUSIONS: The information available to applicants from public access sources regarding interview scheduling is minimal, unstandardized, and unreliable. Notably lacking were policies that only offer as many interviews as slots available, dates when applicants can expect to be notified of interview offers, and notification of declines. Providing such information to applicants in a standardized way may improve satisfaction with the interview scheduling process.


Subject(s)
Internship and Residency , Personnel Selection , Humans , United States
5.
J Surg Educ ; 76(1): 25-35, 2019.
Article in English | MEDLINE | ID: mdl-30195662

ABSTRACT

BACKGROUND: Curricular changes at a mid-sized surgical training program were developed to rebalance clinical rotations, optimize education over service, decrease the size of service teams, and integrate apprenticeship-type experiences. This study quantifies the operative experience before and after implementation as part of a mixed-methods program evaluation. STUDY DESIGN: Retrospective review of case-log data and data from the Accreditation Council for Graduate Medical Education (ACGME) and the American College of Surgeons National Surgical Quality Improvement Program: quality in-training initiative to evaluate case volume pre- and postintervention. RESULTS: 11,365 cases, excluding "first-assistant" and "endoscopic" cases, were logged for an average of 291 and 263 cases/resident pre- and postintervention, respectively. Average case volume increased significantly for postgraduate year (PGY) 3 residents and decreased significantly for PGY 4 residents between the two time periods. Variability was observed among residents at the same PGY level both pre- and postintervention, with coefficients of variation of 6.0% to 34.1% in 2014 to 2015 and 11.2% to 66.8% in 2015 to 2016. Inter-resident variability persisted when comparing a specific procedure between ACGME case-log and quality in-training initiative data sets. CONCLUSION: The data suggest that inter-resident variability in case load is not an artifact of case logging behavior alone, but may reflect personal preferences and choices in case selection that are not impacted by curriculum change. Logging behavior and accuracy of case-logs may contribute to variability. The shift in case load from PGY 4 to PGY 3 after curriculum implementation requires validation by ongoing analysis of ACGME case-log data.


Subject(s)
Curriculum , Internship and Residency/methods , Medical Records , Specialties, Surgical/education , Evaluation Studies as Topic , Program Evaluation , Retrospective Studies
6.
J Am Coll Surg ; 224(6): 1020, 2017 06.
Article in English | MEDLINE | ID: mdl-28550881
7.
J Am Coll Surg ; 222(6): 1096-7, 2016 06.
Article in English | MEDLINE | ID: mdl-27234631
9.
Am Surg ; 76(11): 1185-8, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21140682

ABSTRACT

The surgical residency at Maine Medical Center is the only surgical residency in Maine. Established in 1947, it presently graduates four categorical residents/year. The residency is a classic example of a "hybrid" residency, retaining the benefits of a community program in terms of large operative experience in a wide variety of procedures, while at the same time allowing for academic exposure through a university affiliation.


Subject(s)
Education, Medical, Graduate/organization & administration , General Surgery/education , Internship and Residency/organization & administration , Hospital Design and Construction , Humans , Maine
11.
N Engl J Med ; 360(21): 2191-201, 2009 May 21.
Article in English | MEDLINE | ID: mdl-19458364

ABSTRACT

BACKGROUND: Arteriovenous graft stenosis leading to thrombosis is a major cause of complications in patients undergoing hemodialysis. Procedural interventions may restore patency but are costly. Although there is no proven pharmacologic therapy, dipyridamole may be promising because of its known vascular antiproliferative activity. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of extended-release dipyridamole, at a dose of 200 mg, and aspirin, at a dose of 25 mg, given twice daily after the placement of a new arteriovenous graft until the primary outcome, loss of primary unassisted patency (i.e., patency without thrombosis or requirement for intervention), was reached. Secondary outcomes were cumulative graft failure and death. Primary and secondary outcomes were analyzed with the use of a Cox proportional-hazards regression with adjustment for prespecified covariates. RESULTS: At 13 centers in the United States, 649 patients were randomly assigned to receive dipyridamole plus aspirin (321 patients) or placebo (328 patients) over a period of 4.5 years, with 6 additional months of follow-up. The incidence of primary unassisted patency at 1 year was 23% (95% confidence interval [CI], 18 to 28) in the placebo group and 28% (95% CI, 23 to 34) in the dipyridamole-aspirin group, an absolute difference of 5 percentage points. Treatment with dipyridamole plus aspirin significantly prolonged the duration of primary unassisted patency (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P=0.03) and inhibited stenosis. The incidences of cumulative graft failure, death, the composite of graft failure or death, and serious adverse events (including bleeding) did not differ significantly between study groups. CONCLUSIONS: Treatment with dipyridamole plus aspirin had a significant but modest effect in reducing the risk of stenosis and improving the duration of primary unassisted patency of newly created grafts. (ClinicalTrials.gov number, NCT00067119.)


Subject(s)
Aspirin/therapeutic use , Dipyridamole/therapeutic use , Graft Occlusion, Vascular/prevention & control , Platelet Aggregation Inhibitors/therapeutic use , Renal Dialysis , Thrombosis/prevention & control , Aspirin/adverse effects , Delayed-Action Preparations , Dipyridamole/adverse effects , Double-Blind Method , Drug Therapy, Combination , Female , Graft Occlusion, Vascular/epidemiology , Humans , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Proportional Hazards Models , Renal Dialysis/adverse effects , Thrombosis/epidemiology
12.
Transplantation ; 85(11): 1588-94, 2008 Jun 15.
Article in English | MEDLINE | ID: mdl-18551064

ABSTRACT

BACKGROUND: Compared with standard donors, kidneys recovered from donors after cardiac death (DCD) exhibit higher rates of delayed graft function (DGF), and DCD livers demonstrate higher rates of biliary ischemia, graft loss, and worse patient survival. Current practice limits the use of these organs based on time from donor extubation to asystole, but data to support this is incomplete. We hypothesized that donor postextubation parameters, including duration and severity of hemodynamic instability or hypoxia might be a better predictor of subsequent graft function. METHODS: We performed a retrospective examination of the New England Organ Bank DCD database, concentrating on donor factors including vital signs after withdrawal of support. RESULTS: Prolonged, severe hypotension in the postextubation period was a better predictor of subsequent organ function that time from extubation to asystole. For DCD kidneys, this manifested as a trend toward increased DGF. For DCD livers, this manifested as increased rates of poor outcomes. Maximizing the predictive value of this test in the liver cohort suggested that greater than 15 min between the time when the donor systolic blood pressure drops below 50 mm Hg and flush correlates with increased rates of diffuse biliary ischemia, graft loss, or death. Donor age also correlated with worse outcome. CONCLUSIONS: Time between profound instability and cold perfusion is a better predictor of outcome than time from extubation to asystole. If validated, this information could be used to predict DGF after DCD renal transplant and improve outcomes after DCD liver transplant.


Subject(s)
Death , Hypotension/etiology , Kidney Transplantation/physiology , Liver Transplantation/physiology , Tissue Donors , Tissue and Organ Procurement/methods , Ventilator Weaning/adverse effects , Adult , Age Factors , Blood Pressure/physiology , Female , Follow-Up Studies , Humans , Hypotension/epidemiology , Hypotension/physiopathology , Incidence , Intubation, Intratracheal , Kidney Transplantation/methods , Liver Transplantation/methods , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Survival Rate/trends , United States/epidemiology
13.
Transplantation ; 81(10): 1368-71, 2006 May 27.
Article in English | MEDLINE | ID: mdl-16732170

ABSTRACT

BACKGROUND: To stimulate organ donation, an organ procurement organization (OPO)-wide effort was undertaken to increase donors after cardiac death (DCD) over a 5-year period. This included commonality of protocols, pulsatile perfusion of kidneys, centralization of data and a regional allocation variance designed to minimize cold ischemia times and encourage adoption of DCD protocols at transplant centers. RESULTS: In one OPO, eight centers initiated DCD programs in 11 hospitals. A total of 52 DCD donors were procured, increasing from four in 1999 to 21 in 2003. Eleven donors had care withdrawn in the operating room, whereas 41 had care withdrawn in the ICU. In all, 91 patients received renal transplants from these 52 donors (12 kidneys discarded, one double transplant), whereas 5 patients received liver transplants. One-, two-, and three-year kidney graft survival rates were 90%, 90%, and 82%, respectively. Fifty-five percent of patients needed at least one session of hemodialysis postoperatively. Mean recipient hospital length of stay was 11.1+/-6 days. Mean creatinine levels at 3, 6, 12, and 24 months were 1.65, 1.40, 1.41, and 1.40, respectively. CONCLUSIONS: DCD donors can be an important source of donor organs and provide excellent overall outcomes. Regional cooperation and a prospectively considered allocation and distribution system are important considerations in stimulating DCD programs.


Subject(s)
Death , Tissue Donors/supply & distribution , Tissue and Organ Harvesting/statistics & numerical data , Tissue and Organ Procurement/standards , Adult , Humans , Kidney Transplantation/statistics & numerical data , Middle Aged , Tissue and Organ Harvesting/methods , Tissue and Organ Harvesting/standards , Tissue and Organ Procurement/methods , Tissue and Organ Procurement/statistics & numerical data
14.
Clin Trials ; 2(5): 400-12, 2005.
Article in English | MEDLINE | ID: mdl-16317809

ABSTRACT

BACKGROUND: Surgically created arteriovenous (AV) grafts are the most common type of hemodialysis vascular access in the United States, but fail frequently due to the development of venous stenosis. The Dialysis Access Consortium (DAC) Aggrenox Prevention of Access Stenosis Trial tests the hypothesis that Aggrenox (containing dipyridamole and aspirin) can prevent stenosis and prolong survival of arteriovenous grafts. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled trial that will enroll 1056 subjects over four years with one-half year follow-up. Subjects undergoing placement of a new AV graft for hemodialysis are randomized to treatment with Aggrenox or placebo immediately following access surgery. The primary outcome is primary unassisted patency defined as the time from access placement until thrombosis or an access procedure carried out to maintain or restore patency. The major secondary outcome is cumulative access patency. Monthly access flow monitoring is incorporated in the study design to enhance detection of a hemodynamically significant access stenosis before it leads to thrombosis. RESULTS: This paper describes the key issues in trial design, broadly including: 1) ethical issues surrounding the study of a clinical procedure that, although common, is no longer the clinical intervention of choice; 2) acceptable risk (bleeding) from the primary intervention; 3) inclusion of subjects already receiving a portion of the study intervention; 4) inclusion of subjects with incident rather than prevalent qualifying clinical conditions; 5) timing of the study intervention to balance safety and efficacy concerns; and 6) the selection of primary and secondary study endpoints. CONCLUSIONS: This is the first, large, multicenter trial evaluating a pharmacologic approach to prevent AV graft stenosis and failure, an important and costly problem in this patient population. Numerous design issues were addressed in implementing the trial and these will form a roadmap for future trials in this area.


Subject(s)
Arteriovenous Shunt, Surgical , Graft Occlusion, Vascular/prevention & control , Randomized Controlled Trials as Topic , Renal Dialysis , Algorithms , Aspirin/pharmacology , Aspirin/therapeutic use , Aspirin, Dipyridamole Drug Combination , Delayed-Action Preparations/therapeutic use , Dipyridamole/pharmacology , Dipyridamole/therapeutic use , Drug Combinations , Humans , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation Inhibitors/therapeutic use , Research Design , Sample Size , Vascular Patency/drug effects
15.
Clin Trials ; 2(5): 413-22, 2005.
Article in English | MEDLINE | ID: mdl-16317810

ABSTRACT

BACKGROUND: The Dialysis Access Consortium (DAC) was developed to investigate interventions to improve hemodialysis vascular access outcomes. The autogenous arteriovenous fistula created by direct connection of native artery to vein is the recommended vascular access for hemodialysis. However, it fails frequently due to clotting after surgery. PURPOSE: The DAC Early AV Fistula Thrombosis Trial tests the hypothesis that clopidogrel can prevent early fistula failure and increase the number of fistulas that ultimately become usable for hemodialysis access. This is one of two initial and concurrent trials being performed by the DAC. The companion trial investigates pharmacologic approaches to prevent venous stenosis leading to AV graft failure. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled trial that will enroll 1,284 patients over four years. Patients undergoing creation of a new native arteriovenous (AV) fistula are randomized to treatment with clopidogrel or placebo for six weeks following fistula creation surgery. The primary outcome is fistula patency at six weeks. The major secondary outcome is fistula suitability for dialysis. RESULTS: This paper examines key aspects of this study that have broad relevance to trial design including: 1) the selection of an intermediate event as the primary outcome, 2) timing of the intervention to balance efficacy and safety concerns, 3) ethical considerations arising from required modifications of concomitant drug therapy, and 4) choosing an efficacy or effectiveness evaluation of the intervention. CONCLUSIONS: This is the first, large, multicenter trial evaluating a pharmacologic approach to prevent early AV fistula failure and promote more usable fistulas for hemodialysis. The methodologic challenges identified and addressed during the development of this trial should help to inform the design of future vascular access trials, and are relevant to clinical trials addressing a wide range of questions.


Subject(s)
Arteriovenous Shunt, Surgical , Graft Occlusion, Vascular/prevention & control , Randomized Controlled Trials as Topic , Renal Dialysis , Aspirin/therapeutic use , Clopidogrel , Drug Therapy, Combination , Humans , Multicenter Studies as Topic , Platelet Aggregation Inhibitors/therapeutic use , Research Design , Ticlopidine/analogs & derivatives , Ticlopidine/therapeutic use , Treatment Outcome
16.
Am J Transplant ; 5(9): 2289-96, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16095511

ABSTRACT

Understanding the additional life-years given to patients by deceased organ donors is necessary as substantial investments are being proposed to increase organ donation. Data were drawn from the Scientific Registry of Transplant Recipients. All patients placed on the wait-list as eligible to receive or receiving a deceased donor solid organ transplant between 1995 and 2002 were studied. The benefit of transplant was determined by the difference in the expected survival experiences of transplant recipients and candidates expecting transplant soon. An average organ donor provides 30.8 additional life-years distributed over an average 2.9 different solid organ transplant recipients, whereas utilization of all solid organs from a single donor provides 55.8 additional life-years spread over six organ transplant recipients. The relative contribution of the different organs to the overall life-year benefit is higher for liver, heart and kidney, and lowest for lung and pancreas. The life-year losses from unprocured and unused organs are comparable to suicide, congenital anomalies, homicide or perinatal conditions and half that of HIV. Approximately 250,000 additional life-years could be saved annually if consent for potential deceased donors could be increased to 100%. Therefore, increasing organ donation should be considered among our most important public health concerns.


Subject(s)
Tissue Donors , Tissue and Organ Harvesting/methods , Tissue and Organ Procurement/methods , Adolescent , Adult , Cadaver , Child , Child, Preschool , Female , Graft Survival , Heart Transplantation/methods , Histocompatibility Testing , Humans , Infant , Infant, Newborn , Kidney Transplantation/methods , Liver Transplantation/methods , Living Donors , Lung Transplantation/methods , Male , Middle Aged , Models, Statistical , Organ Transplantation , Pancreas Transplantation/methods , Registries , Sensitivity and Specificity , Statistics as Topic , Time Factors , Treatment Outcome , Waiting Lists
17.
Am J Transplant ; 4(4): 569-73, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15023149

ABSTRACT

Initiatives aimed at increasing organ donation can be considered health care interventions, and will compete with other health care interventions for limited resources. We have developed a model capable of calculating the cost-utility of organ donor initiatives and applied it to Donor Action, a successful international program designed to optimize donor practices. The perspective of the payer in the Canadian health care system was chosen. A Markov model was developed to estimate the net present value incremental lifetime direct medical costs and quality adjusted life years (QALYs) as a consequence of increased kidney transplantation rates. Cost-saving and cost-effectiveness thresholds were calculated. The effects of changing the success rate and time frame of the intervention was examined as a sensitivity analysis. Transplantation results in a gain of 1.99 QALYs and a cost savings of Can$104,000 over the 20-year time frame compared with waiting on dialysis. Implementation of an intervention such as Donor Action, which produced as few as three extra donors per million population, would be cost-effective at a cost of Can$1.0 million per million population. The cost-effectiveness of Donor Action and other organ donor initiatives compare favorably to other health care interventions. Organ donation may be underfunded in North America.


Subject(s)
Tissue and Organ Procurement/economics , Tissue and Organ Procurement/methods , Canada , Cost-Benefit Analysis , Health Care Costs , Humans , Kidney Transplantation/economics , Kidney Transplantation/methods , Markov Chains , Quality-Adjusted Life Years , Sensitivity and Specificity , Time Factors
18.
Transplantation ; 75(12): 1940-5, 2003 Jun 27.
Article in English | MEDLINE | ID: mdl-12829891

ABSTRACT

BACKGROUND: Outcomes of expanded criteria donor (ECD) kidney transplants are known to be superior to dialysis but inferior to transplant with a standard donor. Because of recent policy changes, ECD kidneys will be offered only to patients who have agreed to consider such an organ in advance. There is wide variation in opinion concerning the composition of ECD wait lists. However, the relative benefits of accepting an ECD versus waiting for a standard donor have not been quantified. METHODS: A Markov model was developed to determine when an individual patient should accept or reject an offer of an ECD kidney to optimize their personal expected quality-adjusted life years (QALY). Input variables were estimated from the United States Renal Data System (USRDS) database using a sample of 35,030 recipients. RESULTS: Recipients of ECD kidneys waited 77 days longer for transplant than recipients of standard donors. The average patient could wait 3.2 years longer, in addition to the time they have already waited, for a standard donor than an ECD and expect equivalent QALYs. Selected subsets revealed differences in wait times that equated QALYs for ECD and standard donors: African American, 4.4 years; age under 30, 4.0 years; age over 60, 11 months. CONCLUSIONS: Existing policy is likely to be in the best interests of only certain sets of patients awaiting cadaveric kidney transplantation unless ECDs dramatically reduce expected waiting for transplantation. This is most possible in elderly patients because of the short wait-time reduction required to make ECDs beneficial. Data reported here have been supplied by the USRDS. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US Government. The data and analyses reported in the 2001 Annual Report of the United States Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients have been supplied by the United Network for Organ Sharing and University Renal Research and Education Association under contract with Health and Human Services. The authors alone are responsible for reporting and interpreting of these data.


Subject(s)
Kidney Transplantation/statistics & numerical data , Kidney , Patient Selection , Tissue Donors/supply & distribution , Databases, Factual/statistics & numerical data , Disease-Free Survival , Graft Survival , Humans , Markov Chains , Quality of Life , Time Factors , United States , Waiting Lists
19.
Liver Transpl ; 9(1): 22-30, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12514769

ABSTRACT

ABO-incompatible liver transplants (LTX) have been associated with a high risk of antibody-mediated rejection, poor patient and graft survival, and a high risk of vascular thrombosis and ischemic bile duct complications. We used pretransplantation and posttransplantation double-volume total plasma exchange (TPE), splenectomy, and quadruple immunosuppression (cyclophosphamide or mycophenolate mofetil, prednisone, cyclosporine or tacrolimus, and OKT3 induction) in 14 patients receiving ABO-incompatible LTX between June 1992 and February 2001: A(1) to O (seven), B to O (two), B to A (two), A to B (one), AB to A (one), and AB to O (one). Actuarial 1- and 5-year patient and graft survival rates are 71.4% and 61.2 % and 71.4% and 61.2%, respectively, with a mean follow-up of 62.9 +/- 39.4 months. Ten acute cellular rejections occurred, and the mean time to the first episode was 62 +/- 33 days. All were steroid sensitive. No antibody-mediated rejection or vascular thromboses occurred. Pretransplantation pre-TPE immunoglobulin (Ig) G mean isohemagglutinin titers were 262 +/- 326, compared with pretransplantation post-TPE titers of 65 +/- 103 (P =.04). Eight of nine patients with measurable titers before and after TPE achieved a reduction in titers. The mean number of posttransplantation TPE was 5.5 +/- 4.1 (range, 0 to 12), and the last TPE was on postoperative day 9.4 +/- 5.3. IgG isohemagglutinin titers 2 weeks posttransplantation had increased to 153 +/- 309 (P =.03 compared with pretransplantation pre-TPE IgG). ABO-incompatible liver transplantations can be performed with acceptable patient and graft survival rates with a low risk of antibody-mediated rejection with a combination of TPE, splenectomy, and quadruple immunosuppression. Recovery of isohemagglutinin antibody levels without humoral rejection suggests that accommodation may be the protective mechanism preventing late antibody-mediated rejection.


Subject(s)
Liver Transplantation/immunology , ABO Blood-Group System/immunology , Adolescent , Adult , Aged , Antibiotic Prophylaxis , Clinical Protocols , Female , Graft Rejection , Hemagglutinins/immunology , Humans , Immune Tolerance , Immunosuppressive Agents/therapeutic use , Liver Transplantation/methods , Male , Middle Aged , Plasma Exchange , Splenectomy
20.
Kidney Int ; 62(6): 2272-80, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12427156

ABSTRACT

BACKGROUND: Vascular access dysfunction is the most important cause of morbidity and hospitalization in the hemodialysis population in the United States at a cost of well over one billion dollars per annum. Venous neointimal hyperplasia characterized by stenosis and subsequent thrombosis, is the major cause of polytetrafluoroethylene (PTFE) dialysis graft failure. Despite the magnitude of the problem, there are currently no effective therapies for the prevention or treatment of venous neointimal hyperplasia in PTFE dialysis grafts. We believe that this is partly due to the lack of a validated large animal model of arteriovenous stenosis that could be used to test out novel interventions. METHODS: Seven-centimeter PTFE loop grafts were placed between the femoral artery and vein of domestic pigs. The grafts were removed at 2, 4, 7, 14 and 28 days after surgery and subjected to a detailed histological and immunohistochemical examination. RESULTS: Significant neointimal hyperplasia and venous stenosis developed by 28 days at the graft-vein anastomosis. There was minimal neointimal hyperplasia at the graft-artery anastomosis. Venous neointimal hyperplasia (VNH) was characterized by (a) the presence of smooth muscle cells/myofibroblasts; (b) angiogenesis within both the neointima and adventitia; and (c) the presence of an active macrophage cell layer lining the PTFE graft material. These results are very similar to the human lesion previously described by us in dialysis patients. CONCLUSIONS: We have developed and validated a pig model of venous neointimal hyperplasia that is very similar to the human lesion. We believe that this is an ideal model in which to test out novel interventions for the prevention and treatment of clinical hemodialysis vascular access dysfunction.


Subject(s)
Blood Vessel Prosthesis , Graft Occlusion, Vascular/pathology , Animals , Arteriovenous Shunt, Surgical , Cell Division , Constriction, Pathologic , Disease Models, Animal , Dogs , Endothelium, Vascular/pathology , Hyperplasia , Macrophages/pathology , Muscle, Smooth, Vascular/pathology , Polytetrafluoroethylene , Renal Dialysis , Sheep , Sus scrofa , Tunica Intima/pathology
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