Studying moral distress (MD) and moral injury (MI) among inpatient and outpatient healthcare professionals during the COVID-19 pandemic.

BACKGROUND: COVID-19 increased moral distress (MD) and moral injury (MI) among healthcare professionals (HCPs). MD and MI were studied among inpatient and outpatient HCPs during March 2022. OBJECTIVES: We sought to examine (1) the relationship between MD and MI; (2) the relationship between MD/MI and pandemic-related burnout and resilience; and (3) the degree to which HCPs experienced pandemic-related MD and MI based on their background. METHODS: A survey was conducted to measure MD, MI, burnout, resilience, and intent to leave healthcare at 2 academic medical centers during a 4-week period. A convenience sample of 184 participants (physicians, nurses, residents, respiratory therapists, advanced practice providers) completed the survey. In this mixed-methods approach, researchers analyzed both quantitative and qualitative survey data and triangulated the findings. RESULTS: There was a moderate association between MD and MI (r = .47, P < .001). Regression results indicated that burnout was significantly associated with both MD and MI (P = .02 and P < .001, respectively), while intent to leave was associated only with MD (P < .001). Qualitative results yielded 8 sources of MD and MI: workload, distrust, lack of teamwork/collaboration, loss of connection, lack of leadership, futile care, outside stressors, and vulnerability. CONCLUSIONS: While interrelated conceptually, MD and MI should be viewed as distinct constructs. HCPs were significantly impacted by the COVID-19 pandemic, with MD and MI being experienced by all HCP categories. Understanding the sources of MD and MI among HCPs could help to improve well-being and work satisfaction.

Racial differences in incident de novo donor-specific anti-HLA antibody among primary renal allograft recipients: results from a single center cohort study.

Controversy exists as to whether African American (AA) transplant recipients are at risk for developing de novo donor-specific anti-human leucocyte antigen (HLA) antibody (dnDSA). We studied 341 HLA-mismatched, primary renal allograft recipients who were consecutively transplanted between 3/1999 and 12/2010. Sera were collected sequentially pre- and post-transplant and tested for anti-HLA immunoglobulin G (IgG) via single antigen bead assay. Of the 341 transplant patients (225 AA and 116 non-AA), 107 developed dnDSA at a median of 9.2 months post-transplant. AA patients had a 5-year dnDSA incidence of 35%. This was significantly higher than the 5-year dnDSA incidence for non-AA patients (21%). DQ mismatch (risk) and receiving a living-related donor (LRD) transplant (protective) were transplant factors associated with dnDSA. Within the AA patient cohort, HLA-DQ mismatch, not-receiving a LRD transplant, nonadherence and BK viraemia were the most common factors associated with early dnDSA (occurring <24 months post-transplant). Nonadherence and pretransplant diabetes history were the strong precursors to late dnDSA. Despite the higher rates of dnDSA in the AA cohort, post-dnDSA survival was the same in AA and non-AA patients. This study suggests that DQ matching, increasing LRD transplantation in AA patients and minimizing under-immunosuppression will be key to preventing dnDSA.

Incidence and impact of anti-HLA-DP antibodies in renal transplantation.

BACKGROUND: The role of anti-HLA-DP antibodies in renal transplantation is poorly defined. This study describes the impact of donor (donor-specific antibody [DSA]) and non-donor-specific antibodies against HLA-DP antigens in renal transplant patients. METHODS: Of 195 consecutive patients transplanted between September 2009 and December 2011, 166 primary kidney recipients and their donors were typed (high-resolution) for DP antigens. Sera taken pre-transplant and at 1, 3, 6, 9, and 12 months, and annually post-transplant were retrospectively tested for anti-DP antibodies using single-antigen beads. RESULTS: In 81 (49%) patients, anti-DP antibodies were found; 64% (n=52) of patients were positive in the pre-transplant samples and 36% (n=29) were positive exclusively post-transplant. The median time from transplantation to antibody was 20.9 months. Fifty-five percent (n=16) of the de novo anti-DP antibodies were accompanied by another de novo DSA. Anti-DP antibody-positive patients had a higher rate of rejection (compared with anti-DP antibody-negative patients, P=.01). The estimated glomerular filtration rate declined more with anti-DP antibodies (-5.5% vs +26%). CONCLUSIONS: Antibodies against HLA-DP antigens are common. De novo anti-DP antibodies commonly appear after acute rejection and accompany DSA, which makes it difficult to determine whether anti-DP antibodies are the cause or the consequence of graft injury.

Examining Hemodialysis Reliable Outflow catheter performance and cost in hemodialysis access.

BACKGROUND: The Hemodialysis Reliable Outflow (HeRO) vascular access device is a hybrid polytetrafluoroethylene graft-stent construct designed to address central venous occlusive disease. Although initial experience has demonstrated excellent mid-term patency rates, subsequent studies have led to external validity questions. The purpose of this study was to examine a single center experience with this vascular access device in challenging access cases with associated costs. METHODS: A retrospective study representing the authors' cumulative HeRO vascular access device experience was undertaken. The primary endpoint was graft failure or death, with secondary endpoints including secondary intervention rates and cost. RESULTS: Forty-one patients with 15,579 HeRO days and a mean of 12.7 ± 1.5 mo with the vascular access device were available for analysis. Secondary patency was 81.6% at 6 mo and 53.7% at 12 mo. The reintervention rate was 2.84 procedures per HeRO vascular access device year. Associated HeRO costs related to subsequent procedures were estimated at $34,713.63 per patient/y. CONCLUSIONS: These data on the patency and primary outcome data diverge significantly from initial multicenter studies and represent a real-world application of this technology. It is costly to maintain patency. Use of HeRO vascular access devices should be judicious with outcome expectations reduced.

The Resource Costs of Maintaining Learner Utilization of a Simulation Center During the COVID-19 Pandemic.

BACKGROUND: Despite advances in online education during the COVID-19 pandemic, its impact on surgical simulation remains unclear. The aim of this study was to compare the costs and resources required to maintain simulation training in the pandemic and to evaluate how it affected exposure of medical students to simulation during their surgical clerkship. METHODS: The number of learners, contact hours, staff hours, and costs were collected from a multi-departmental simulation center of a single academic institution in a retrospective fashion. Utilization and expenditure metrics were compared between the first quarter of academic years 2018-2020. Statistical analysis was performed to evaluate potential differences between overall resource utilization before and during the pandemic, and subgroup analysis was performed for the resources required for the training of the third-year medical students. RESULTS: The overall number of learners and contact hours decreased during the first quarter of the academic year 2020 in comparison with 2019 and 2018. However, the staff hours increased. In addition, the costs for PPE increased for the same periods of time. In the subgroup analysis of the third-year medical students, there was an increase in the number of learners, as well as in the staff hours and in the space required to perform the simulation training. DISCUSSION: Despite an increase in costs and resources spent on surgical simulation during the pandemic, the utilization by academic entities has remained unaffected. Further studies are required to identify potential solutions to lower simulation resources without a negative impact on the quality of surgical simulation.

Is it possible to train surgeons for rural Africa? A report of a successful international program.

BACKGROUND: The critical shortage of surgeons and access to surgical care in Africa is increasingly being recognized as a global health crisis. Across Africa, there is only one surgeon for every 250,000 people and only one for every 2.5 million of those living in rural areas. Surgical diseases are responsible for approximately 11.2% of the total global burden of disease. Even as the importance of treating surgical disease is being recognized, surgeons in sub-Saharan Africa are leaving rural areas and their countries altogether to practice in more desirable locations. METHODS: The Pan-African Academy of Christian Surgeons (PAACS) was formed in 1997 as a strategic response to this profound need for surgical manpower. It is training surgical residents through a 5-year American competency-based model. Trainees are required to be of African origin and a graduate of a recognized medical school. RESULTS: To date, PAACS has established six training programs in four countries. During the 2009-2010 academic year, there were 35 residents in training. A total of 18 general surgeons and one pediatric surgeon have been trained. Two more general surgeons are scheduled to finish training in 2011. Four graduates have gone on to subspecialty training, and the remaining graduates are practicing general surgery in rural and underserved urban centers in Angola, Guinea-Conakry, Ghana, Cameroon, Republic of Congo, Kenya, Ethiopia, and Madagascar. CONCLUSIONS: The PAACS has provided rigorous training for 18 African general surgeons, one of whom has also completed pediatric surgery training. To our knowledge, this is the only international rural-based surgical training program in Africa.

Development and Assessment of a Systematic Approach for Detecting Disparities in Surgical Access.

Importance: Although optimal access is accepted as the key to quality care, an accepted methodology to ascertain potential disparities in surgical access has not been defined. Objective: To develop a systematic approach to detect surgical access disparities. Design, Setting, and Participants: This cross-sectional study used publicly available data from the Health Cost and Utilization Project State Inpatient Database from 2016. Using the surgical rate observed in the 5 highest-ranked counties (HRCs), the expected surgical rate in the 5 lowest-ranked counties (LRCs) in North Carolina were calculated. Patients 18 years and older who underwent an inpatient general surgery procedure and patients who underwent emergency inpatient cholecystectomy, herniorrhaphy, or bariatric surgery in 2016 were included. Data were collected from January to December 2016, and data were analyzed from March to July 2020. Exposures: Health outcome county rank as defined by the Robert Wood Johnson Foundation. Main Outcomes and Measures: The primary outcome was the proportional surgical ratio (PSR), which was the disparity in surgical access defined as the observed number of surgical procedures in the 5 LRCs relative to the expected number of procedures using the 5 HRCs as the standardized reference population. Results: In 2016, approximately 1.9 million adults lived in the 5 HRCs, while approximately 246 854 lived in the 5 LRCs. A total of 28 924 inpatient general surgical procedures were performed, with 4521 being performed in those living in the 5 LRCs and 24 403 in those living in the 5 HRCs. The rate of general surgery in the 5 HRCs was 13.09 procedures per 1000 population. Using the 5 HRCs as the reference, the PSR for the 5 LRCs was 1.40 (95% CI, 1.35-1.44). For emergent/urgent cholecystectomy, the PSR for the 5 LRCs was 2.26 (95% CI, 2.02-2.51), and the PSR for emergent/urgent herniorrhaphy was 1.83 (95% CI, 1.33-2.45). Age-adjusted rate of obesity (body mass index [calculated as weight in kilograms divided by height in meters squared] greater than 30), on average, was 36.6% (SD, 3.4) in the 5 LRCs vs 25.4% (SD, 4.6) in the 5 HRCs (P = .002). The rate of bariatric surgery in the 5 HRCs was 33.07 per 10 000 population with obesity. For the 5 LRCs, the PSR was 0.60 (95% CI, 0.51-0.69). Conclusions and Relevance: The PSR is a systematic approach to define potential disparities in surgical access and should be useful for identifying, investigating, and monitoring interventions intended to mitigate disparities in surgical access that effects the health of vulnerable populations.

Aortoiliac intervention with distal protection to salvage a heterotopic renal transplant.

A case of substantial debris captured by an embolic protection device placed in a patient's transplanted renal artery during common iliac artery angioplasty and stent placement is presented. To the authors knowledge, no previous literature exists pertaining to renal artery protection in patients with a history of a heterotopic renal transplant undergoing aortoiliac endovascular interventions.

Real-time PCR to determine transgene copy number and to quantitate the biolocalization of adoptively transferred cells from EGFP-transgenic mice.

Quantitative real-time PCR (qPCR) is a sensitive technique for the detection and quantitation of specific DNA sequences. Here we describe a Taqman qPCR assay for quantification of tissue-localized, adoptively transferred enhanced green fluorescent protein (EGFP)-transgenic cells. A standard curve constructed from serial dilutions of a plasmid containing the EGFP transgene was (i) highly reproducible, (ii) detected as few as two copies, and (iii) was included in each qPCR assay. qPCR analysis of genomic DNA was used to determine transgene copy number in several mouse strains. Fluorescent microscopy of tissue sections showed that adoptively transferred vascular endothelial cells (VEC) from EGFP-transgenic mice specifically localized to tissue with metastatic tumors in syngeneic recipients. VEC microscopic enumeration of liver metastases strongly correlated with qPCR analysis of identical sections (Pearson correlation 0.81). EGFP was undetectable in tissue from control mice by qPCR. In another study using intra-tumor EGFP-VEC delivery to subcutaneous tumors, manual cell count and qPCR analysis of alternating sections also strongly correlated (Pearson correlation 0.82). Confocal microscopy of the subcutaneous tumor sections determined that visual fluorescent signals were frequently tissue artifacts. This qPCR methodology offers specific, objective, and rapid quantitation, uncomplicated by tissue autofluorescence, and should be readily transferable to other in vivo models to quantitate the biolocalization of transplanted cells.

Case Reporting, Competence, and Confidence: A Discrepancy in the Numbers.

PURPOSE: The Accreditation Council for Graduate Medical Education (ACGME) continues to play an integral role in accreditation of surgical programs. The institution of case logs to demonstrate competency of graduating residents is a key component of evaluation. This study compared the number of vascular cases a surgical resident has completed according to the ACGME operative log to their operative proficiency, quality of anastomosis, operative experience, and confidence in both a simulation and operative setting. MATERIALS AND METHODS: General surgery residents ranging from PGY 1 to 5 participated in a simulation laboratory in which they completed an end-to-side vascular anastomosis. Each participant was given a weighted score based on technical proficiency and anastomosis quality using a previously validated Global Rating Scale (Duran et al, 2014). These scores were correlated to the General Surgery Milestones. Participants completed preoperative and postoperative surveys assessing resident operative experience using the 4-level Zwisch scale (DaRosa et al., 2013), confidence with vascular procedures and confidence performing simulated anastomoses. Confidence was assessed on a scale from 1 to 9 (not confident to extremely confident). Case logs were recorded for each participant. An IRB approved questionnaire was distributed to assess preoperative and postoperative roles of both the resident physician and faculty, with a defined goal. Univariate and multivariate analysis was performed. RESULTS: Twenty-one general surgery residents were evaluated in the simulation laboratory and 8 residents were assessed intraoperatively. The residents were evenly distributed throughout clinical years. Groups of residents were divided into quartiles based upon the number of vascular cases recorded in the ACGME database. No correlation was found between number of cases, Milestones score and the weighted score (p = 0.94). No statistical significance was found between confidence and quality of anastomosis (p = 0.1). Resident operative experience per the Zwisch scale was categorized most commonly as "Smart Help" by both the trainee and attending surgeon, despite mean resident confidence ratings of 6.67 (± 1.61) with vascular procedures. CONCLUSIONS: ACGME case logs, which are utilized to assess readiness for completion of general surgery residency, may not be indicative of a resident's operative competency and technical proficiency. Confidence is not correlated with technical ability. Faculty and resident insight as to their role in a procedure differ, as faculty feel that they are providing less help than the resident perceives. Careful examination of resident operative technique is the best measure of competency.

Duty-hour restrictions and the work of surgical faculty: results of a multi-institutional study.

PURPOSE: To examine whether duty-hour restrictions have been consequential for various aspects of the work of surgical faculty and if those consequences differ for faculty in academic and nonacademic general surgery residency programs. METHOD: Questionnaires were distributed in 2004 to 233 faculty members in five academic and four nonacademic U.S. residency programs in general surgery. Participation was restricted to those who had been faculty for at least one year. Ten items on the questionnaire probed faculty work experiences. Results include means, percentages, and t-tests on mean differences. Of the 146 faculty members (63%) who completed the questionnaire, 101 volunteered to be interviewed. Of these, 28 were randomly chosen for follow-up interviews that probed experiences and rationales underlying items on the questionnaire. Interview transcripts (187 single-spaced pages) were analyzed for main themes. RESULTS: Questionnaire respondents and interviewees associated duty-hour restrictions with lowered faculty expectations and standards for residents, little change in the supervision of residents, a loss of time for teaching, increased work and stress, and less satisfaction. No significant differences in these perceptions (p < or = .05) were found for faculty in academic and nonacademic programs. Main themes from the interviews included a shift of routine work from residents to faculty, a transfer of responsibility to faculty, more frequent skill gaps at night, a loss of time for research, and the challenges of controlling residents' hours. CONCLUSIONS: Duty-hour restrictions have been consequential for the work of surgical faculty. Faculty should not be overlooked in future studies of duty-hour restrictions.

How surgical faculty and residents assess the first year of the Accreditation Council for Graduate Medical Education duty-hour restrictions: results of a multi-institutional study.

BACKGROUND: This study examined how surgical residents and faculty assessed the first year of the Accreditation Council for Graduate Medical Education duty-hour restrictions. METHODS: Questionnaires were administered in 9 general-surgery programs during the summer of 2004; response rates were 63% for faculty and 58% for residents (N = 259). Questions probed patient care, the residency program, quality of life, and overall assessments of the duty-hour restrictions. Results include the means, mean deviations, percentage who agree or strongly agree with the hour restrictions, and significance tests. RESULTS: Although most support the restrictions, few maintain that they improved surgical training or patient care. Faculty and residents differed (P < or = .05) on 16 of 21 items. Every difference shows that residents view the restrictions more favorably than faculty. The sex of the resident shaped the magnitude of the gap for 11 of 21 items. CONCLUSIONS: Few believe that duty-hour restrictions improve patient care or resident training. Residents, especially female residents, view the restrictions more favorably than faculty.

Milestones: The Road to Faculty Development.

PURPOSE: Milestones for the assessment of residents in graduate medical education mark a change in our evaluation paradigms. The Accreditation Council for Graduate Medical Education has created milestones and defined them as significant points in development of a resident based on the 6 competencies. We propose that a similar approach be taken for resident assessment of teaching faculty. We believe this will establish parity and objectivity for faculty evaluation, provide improved data about attending surgeons' teaching, and standardize faculty evaluations by residents. METHODS: A small group of advanced surgery educators determined appropriate educational characteristics, resulting in creation of 11 milestones (Fig. 2) that were reviewed by faculty and residents. The residents have historically answered 16 questions, developed by our surgical education committee (Fig. 3), on a 5-point Likert score (never to very often). Three weeks after completing this Likert-type evaluation, the residents were asked to again evaluate attending faculty using the Faculty Milestones evaluation. The residents then completed a survey of 7 questions (scale of 1-9-disagree to strongly agree, neutral = 5), assessing the new milestones and compared with the previous Likert evaluation system. RESULTS: Of 32 surgery residents, 13 completed the Likert evaluations (3760 data points) and 13 completed the milestones evaluations (1800 data points). The number completing both or neither is not known, as the responses are anonymous when used for faculty feedback. The Faculty Milestones attending physicians' scores have far fewer top of range scores (21% vs 42%) and have a wider spread of data giving better indication of areas for improvement in teaching skills. The residents completed 17 surveys (116 responses) to evaluate the new milestones system. Surveys indicated that milestones were easier to use (average rating 6.13 ± 0.42 Standard Error (SE)), effective (6.82 ± 0.39) and efficient (6.11 ± 0.53), and more objective (6.69 ± 0.39/6.75 ± 0.38) than the Likert evaluations are. Average response was 6.47 ± 0.46 for overall satisfaction with the Faculty Milestones evaluation. More surveys were completed than evaluations, as all residents had an opportunity to review both evaluation systems. CONCLUSIONS: Faculty Milestones are more objective in evaluating surgical faculty and mirror the new paradigm in resident evaluations. Residents found this was an easier, more effective, efficient, and objective evaluation of our faculty. Although our Faculty Milestones are designed for surgical educators, they are likely to be applicable with appropriate modifications to other medical educators as well.

Risk Stratification of Human Leukocyte Antigen Class II Donor Specific Antibody Positive Patients by Immunoglobulin G Subclasses.

BACKGROUND: Human leukocyte antigen (HLA) antibodies are a major cause of graft loss in mismatched transplant recipients. However, the time to graft loss resulting from antibody induced injury is unpredictable. The unpredictable nature of antibodies may be related to the subclass of antibodies. In this study, HLA immunoglobulin G (IgG) subclasses were investigated to determine whether a unique IgG subclass composition could better identify those patients at eminent risk for graft loss. METHODS: The serial serum samples from the 57 patients with post-transplant HLA class II donor specific antibodies (DSA) were tested for the three IgG subclasses (IgG1, IgG3, and IgG4). RESULTS: IgG3 and IgG4 were highly prevalent in failed patients compared to functioning patients (82 % vs. 34%, 45% vs. 20%, respectively). IgG3 development showed a distinct subclass trend between failed and functioning patients with poor graft survival (log rank p=0.0006). IgG1 was almost equally abundant in both groups (100% and 97%, respectively). Of the 5 patterns of IgG subclass combinations observed, IgG1+3+ showed the strongest association with graft failure (hazard ratio 3.14, p=0.007). CONCLUSION: Patients with IgG3 subclass HLA DSA showed lower graft survival. Post-transplant monitoring for IgG subclasses rather than total IgG monitoring may identify patients at risk for graft failure.

Characterization of Lewis lung clonal variants in a model of syngeneic pulmonary murine metastases.

Lung cancer is the leading cause of cancer-related mortality world-wide. Since the majority of cancer deaths result from metastatic complications, understanding cellular alterations contributing to organ specific metastases is a continuing cancer research goal. Desirable models involve easy, efficient methodologies for development of pulmonary metastases utilizing genetically related syngeneic tumor cell lines varying in clonogenic frequency and growth rate for comparative studies. This work focused on development and characterization of primary and metastatic Lewis lung subclones (LLCC3, LLC1, LLCab) in a histocompatible C57B1/6 model. Surgical resection of primary tumors utilizing these cell lines resulted in reliable development of pulmonary metastases (> 90% of injected mice), while tail-vein injection proved sporadic (20% of injected mice). The preliminary analysis of selected cell-surface molecules indicates potential genetic differences that may underlie phenotypic variations. The combination of subcutaneous resection methodology and variant cell lines results in robust metastatic lung cancer for testing potential therapeutic interventions.

HLA matching and the United Network for Organ Sharing Allocation System: impact of HLA matching on African-American recipients of cadaveric kidney transplants.

BACKGROUND: A recent proposal supports the elimination of allocation points for human leukocyte antigen (HLA) mismatches (MM) in cadaveric kidney transplantation. The intent is to increase access for some racial groups that might be disadvantaged by the representation of race-specific HLA in a largely white donor pool. We report our experience from two transplant centers that serve a large African American (AA) patient population. METHODS: All cadaveric transplants into AA recipients from 1994 to 2000 (n=162) were included in a retrospective review. RESULTS: Superior graft survival was observed in AA recipients of 0 MM transplants. When induction therapy was used, the graft survival at 3 years for the human leukocyte antigen (HLA)-BDR MM grades given allocation points (0,1,2 MM) was 82% versus only 49% for BDR MM grades not given points (3,4 MM: =0.0022). CONCLUSIONS: Our collective experience demonstrates that AA patients having HLA-BDR MM grades given allocation points had better graft survival. Removing points for HLA from the national allocation system may result in significantly poorer outcome in AA kidney recipients.

Overcoming severe renal ischemia: the role of ex vivo warm perfusion.

BACKGROUND: The ability to effectively utilize kidneys damaged by severe (2 hr) warm ischemia (WI) could provide increased numbers of kidneys for transplantation. The present study was designed to examine the effect of restoring renal metabolism after severe WI insult during ex vivo warm perfusion using an acellular technology. After warm perfusion for 18 hr, kidneys were reimplanted and evaluated for graft function. METHODS: Using a canine autotransplant model, kidneys were exposed to 120 min of WI. They were then either reimplanted immediately, hypothermically machine perfused (4 degrees C) for 18 hr with Belzer's solution, or transitioned to 18 hr of warm perfusion (32 degrees C) with an acellular perfusate before implantation. RESULTS: Warm perfused kidneys with 120 min of WI provided life-sustaining function after transplantation, whereas the control kidneys immediately reimplanted or with hypothermic machine perfusion did not. The mean peak serum creatinine in the warm perfused kidneys was 3.7 mg/dl, with the mean peak occurring on day 2 and normalizing on day 9 posttransplant. CONCLUSIONS: These results indicate that 18 hr of ex vivo warm perfusion of kidneys is feasible. Furthermore, recovery of renal function during warm perfusion is demonstrated, resulting in immediate function after transplantation. The use of ex vivo warm perfusion to recover function in severe ischemically damaged kidneys could provide the basis for increasing the number of transplantable kidneys.

Suppression of Lewis lung tumor development in alpha 1,3 galactosyltransferase knock-out mice.

BACKGROUND: Humans lack the gene alpha 1,3 galactosyltransferase (GalT) and instead produce abundant cytolytic antibodies against cells bearing the antigen [gal alpha1,3 gal] (alphaGal). We have previously studied humoral anti-alphaGal responses in GalT knock-out (GalT KO) mice and shown that murine anti-alphaGal IgM, like human anti-alphaGal IgM, causes extensive complement-mediated cytolysis of GalT+ murine Lewis Lung carcinoma cells (LLCa) in vitro. Here we test the hypothesis that anti-alphaGal immune responses can inhibit the in vivo development of GalT+ tumors. MATERIALS AND METHODS: GalT KO mice orally immunized to produce anti-alphaGal antibodies (n =52) and naïve non-immunized KO mice (n=37) were challenged s.c. with 10(5) LLCa tumor cells. Anti-alphaGal antibody titers were measured before and after LLCa challenge. RESULTS: Anti-alphaGal IgM titers present at challenge correlated with protection from tumor development (p<0.04). Seventy-five percent of mice with titers > or = 1:1280 remained tumor-free versus 43% of naïve mice. Tumor onset was delayed in mice with circulating anti-alphaGal IgM versus naïve animals (p=0.02). LLCa challenge itself induced and augmented anti-alphaGal IgM and post-challenge titers correlated highly with protection from tumor development (p<0.001). No mice with post-challenge anti-alphaGal IgM titers > or = 1:1280 developed tumors, compared to 83% of mice lacking antibody. Inhibition studies showed that 30% of post-challenge IgM recognized LLCa antigens distinct from alphaGal. Anti-alphaGal IgG was low or undetectable both pre- and post challenge and did not affect tumor formation. CONCLUSION: The finding that anti-alphaGal IgM suppresses GaIT+ tumor development in vivo supports the premise that immunotherapy using GalT expression can utilize human anti-alphaGal responses and induce significant anti-tumor effects.

Performance standards improve American Board of Surgery In-Training Examination scores.

PURPOSE: Although several studies have evaluated factors affecting American Board of Surgery In-Training Examination (ABSITE) performance, none has examined the impact of setting a minimally acceptable standard. It was hypothesized that establishing such a criterion would improve ABSITE scores. METHODS: An expectation for residents to score at the 35th percentile or higher was established in 1996. The proportion of test scores above or below the 35th and 50th percentiles for the time periods before and after institution of the standard were compared using Fisher's exact test. The subsequent performance of residents scoring below the 35th percentile was analyzed for the 2 time periods. RESULTS: After the institution of the standard, the proportion of scores below the 35th percentile decreased from 46.7% to 21.9% (p = 0.0005). Similarly, the proportion of scores at or above the national average increased from 42.1% to 65.6% (p = 0.0005). After establishing the standard, fewer residents continued to have scores below the criterion in subsequent years. CONCLUSIONS: Establishing a performance criterion improved ABSITE scores. The decision to institute a standard must be individualized for each program. The rationale for the standard and a plan to assist residents failing to achieve the benchmark must be communicated.

Improved Long-Term Survival in Kidney Transplant Recipients with Donor-Specific HLA Antibodies After Mycophenolic Acid Escalation.

The development of donor specific antibodies (DSA) post transplant has been associated with chronic rejection and graft failure. In a longitudinal study, we have shown that increases in DSA precede rejection by months, thus allowing time for intervention. We hypothesized that mycophenolic acid (MPA) dose increases may reduce and/or stabilize DSA strength and also preserve renal function. Thirty stable DSA positive kidney transplant recipients participated in this Institutional Review Board approved, exploratory, open-label, single center study to assess the efficacy of MPA dose escalation in patients with DSA. MPA escalation was well tolerated and most patients were able to take higher doses for at least two years (duration of the study). In addition, MPA escalation is safe and participants had no significant side effects such as cytomegalovirus and BK infections. Long-term allograft survival of the MPA escalation group was superior when compared with the control group (p = 0.018). This pilot study indicates that escalation of MPA is safe and may stabilize DSA. In addition, five-year follow up demonstrates improved long-term survival with MPA escalation compared with DSA positive recipients receiving the standard of care. Additional studies using larger cohorts are warranted.