Marc L. Melcher

All Publications

• Prehabilitation in our most frail surgical patients: are wearable fitness devices the next frontier? CURRENT OPINION IN ORGAN TRANSPLANTATION Rumer, K. K., Saraswathula, A., Melcher, M. L. 2016; 21 (2): 188-193

  Abstract

  Frailty is the concept of accumulating physiologic declines that make people less able to deal with stressors, including surgery. Prehabilitation is intervention to enhance functional capacity before surgery. Frailty and prehabilitation among transplant populations and the role of wearable fitness tracking devices (WFTs) in delivering fitness-based interventions will be discussed.Frailty is associated with increased complications, longer length of hospital stay and increased mortality after surgery. Frail kidney transplant patients have increased delayed graft function, mortality and early hospital readmission. Frail lung or liver transplant patients are more likely to delist or die on the waitlist. Prehabilitation can mitigate frailty and has resulted in decreased length of hospital stay and fewer postsurgical complications among a variety of surgical populations. Increasingly, WFTs are used to monitor patient activity and improve patient health. Interventions using WFTs have resulted in improved activity, weight loss and blood pressure.Frailty is a measurable parameter that identifies patients at risk for worse health outcomes and can be mitigated through intervention. Prehabilitation to reduce frailty has been shown to improve postsurgical outcomes in a variety of populations. WFTs are being integrated in healthcare delivery for monitoring and changing health behavior with promising results.

  View details for DOI 10.1097/MOT.0000000000000295

  View details for Web of Science ID 000371883900018

  View details for PubMedID 26859220

• Survival Benefit with Kidney Transplants from HLA-Incompatible Live Donors NEW ENGLAND JOURNAL OF MEDICINE Orandi, B. J., Luo, X., Massie, A. B., Garonzik-Wang, J. M., Lonze, B. E., Ahmed, R., Van Arendonk, K. J., Stegall, M. D., Jordan, S. C., Oberholzer, J., Dunn, T. B., Ratner, L. E., Kapur, S., Pelletier, R. P., Roberts, J. P., Melcher, M. L., Singh, P., Sudan, D. L., Posner, M. P., El-Amm, J. M., Shapiro, R., Cooper, M., Lipkowitz, G. S., Rees, M. A., Marsh, C. L., Sankari, B. R., Gerber, D. A., Nelson, P. W., Wellen, J., Bozorgzadeh, A., Gaber, A. O., Montgomery, R. A., Segev, D. L. 2016; 374 (10): 940-950

  Abstract

  A report from a high-volume single center indicated a survival benefit of receiving a kidney transplant from an HLA-incompatible live donor as compared with remaining on the waiting list, whether or not a kidney from a deceased donor was received. The generalizability of that finding is unclear.In a 22-center study, we estimated the survival benefit for 1025 recipients of kidney transplants from HLA-incompatible live donors who were matched with controls who remained on the waiting list or received a transplant from a deceased donor (waiting-list-or-transplant control group) and controls who remained on the waiting list but did not receive a transplant (waiting-list-only control group). We analyzed the data with and without patients from the highest-volume center in the study.Recipients of kidney transplants from incompatible live donors had a higher survival rate than either control group at 1 year (95.0%, vs. 94.0% for the waiting-list-or-transplant control group and 89.6% for the waiting-list-only control group), 3 years (91.7% vs. 83.6% and 72.7%, respectively), 5 years (86.0% vs. 74.4% and 59.2%), and 8 years (76.5% vs. 62.9% and 43.9%) (P<0.001 for all comparisons with the two control groups). The survival benefit was significant at 8 years across all levels of donor-specific antibody: 89.2% for recipients of kidney transplants from incompatible live donors who had a positive Luminex assay for anti-HLA antibody but a negative flow-cytometric cross-match versus 65.0% for the waiting-list-or-transplant control group and 47.1% for the waiting-list-only control group; 76.3% for recipients with a positive flow-cytometric cross-match but a negative cytotoxic cross-match versus 63.3% and 43.0% in the two control groups, respectively; and 71.0% for recipients with a positive cytotoxic cross-match versus 61.5% and 43.7%, respectively. The findings did not change when patients from the highest-volume center were excluded.This multicenter study validated single-center evidence that patients who received kidney transplants from HLA-incompatible live donors had a substantial survival benefit as compared with patients who did not undergo transplantation and those who waited for transplants from deceased donors. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.).

  View details for DOI 10.1056/NEJMoa1508380

  View details for Web of Science ID 000371660000007

  View details for PubMedID 26962729

• Program Factors That Influence American Board of Surgery In-Training Examination Performance: A Multi-Institutional Study. Journal of surgical education Kim, J. J., Gifford, E. D., Moazzez, A., Sidwell, R. A., Reeves, M. E., Hartranft, T. H., Inaba, K., Jarman, B. T., Are, C., Galante, J. M., Amersi, F., Smith, B. R., Melcher, M. L., Nelson, M. T., Donahue, T., Jacobsen, G., Arnell, T. D., Lee, S., Neville, A., De Virgilio, C. 2015; 72 (6): e236-42

  Abstract

  To determine the influence of program strategies, such as program directors' (PD) attitudes about the American Board of Surgery In-Training Examination (ABSITE) and approach to ABSITE preparation, on residents' ABSITE performance.A 17-item questionnaire was sent to PDs at surgical residency programs. The questions were designed to elicit information regarding the educational curriculum, remediation protocols, and opinions relating to the ABSITE. Main outcome measure was categorical resident ABSITE percentile scores from the January 2014 examination. Statistical analysis was performed using the Student t-test, analysis of variance, and linear regression as appropriate.The study was carried out at general surgery residency programs across the country.In total, 15 general surgery residency PDs participated in the study.The PD response rate was 100%. All 460 resident ABSITE scores from the 15 programs were obtained. In total, 10 programs (67%) identified as university affiliated, 4 programs (27%) as independent academic, and 1 program (7%) as hybrid. The mean number of residents per program was 30.7 (range: 15-57). In total, 14 PDs (93%) indicated that an ABSITE review curriculum was in place and 13 PDs (87%) indicated they had a remediation protocol for residents with low ABSITE scores (with differing thresholds of <30th, <35th, and <40th percentile). The median overall ABSITE score for all residents was 61st percentile (interquartile range = 39.5). The mean ABSITE score for each program ranged from 39th to 75th percentile. Program factors associated with higher ABSITE scores included tracking resident reading throughout the year (median 63rd percentile with tracking vs 59th percentile without, p = 0.040) and the type of remediation (by PD: 77th percentile, by PD and faculty: 57th percentile, faculty only: 64th percentile, with Surgical Education and Self-Assessment Program (SESAP): 63rd percentile, outside review course: 43rd percentile; p < 0.001). Programs with a remediation protocol trended toward higher ABSITE scores compared with programs without remediation protocols (median 61st percentile vs 53rd percentile, p = 0.098). Factors not significantly associated with ABSITE performance included number of structured educational hours per week and frequency of ABSITE review sessions.Program factors appear to significantly influence ABSITE performance. Programs where the PD was actively involved in remediation mentorship and the tracking of resident reading achieved higher ABSITE percentile scores on the January 2014 examination. Counterintuitively, residents from programs with a lower ABSITE threshold for remediation performed better on the examination.

  View details for DOI 10.1016/j.jsurg.2015.06.014

  View details for PubMedID 26319103

• Saving Supersick Patients Undergoing Liver Transplant. JAMA surgery Melcher, M. L. 2015; 150 (11): 1073-?

  View details for DOI 10.1001/jamasurg.2015.1881

  View details for PubMedID 26309213

• Identifying Opportunities to Increase the Throughput of Kidney Paired Donation. Transplantation Liu, W., Treat, E., Veale, J. L., Milner, J., Melcher, M. L. 2015; 99 (7): 1410-1415

  Abstract

  Although kidney paired donation (KPD) has led to thousands of transplants, the 2012 KPD Consensus Conference concluded that more could be done. Perceptions are that a large number of match offers never resulted in transplantations, and unfruitful matches have both financial and emotional costs.To describe, quantify, and analyze the unrealized match offers, we studied the matching process from registration to transplantation in the National Kidney Registry, a large KPD registry, over a 25-month period.Of the 3,180 match offers, 454 were turned down. The most common reasons were the donor was not acceptable (50%) and their recipient had unacceptably high donor-specific antibodies (28%). Of the 2,228 accepted offers, 1,335 advanced to the cell-based cross-match stage because 893 of these were part of chains that fell through. Fifty-five of 887 recorded cell-based cross-matches were positive, 20 donors were unacceptable, and 22 recipients had unacceptably high donor-specific antibodies. Six hundred ninety transplantations were performed.Despite the success of KPD, by analyzing the matching process, we identify several strategies to increase the number of KPD transplantations, including recruiting more participants, processing the match offers more quickly at the transplant center level, enhancing the donor preselection tools, improving communication between centers and the registries, and combining desensitization with KPD.

  View details for DOI 10.1097/TP.0000000000000527

  View details for PubMedID 25606799

• Recurrent Hepatocellular Carcinoma and Poorer Overall Survival in Patients Undergoing Left-sided Compared With Right-sided Partial Hepatectomy JOURNAL OF CLINICAL GASTROENTEROLOGY Valenzuela, A., Ha, N. B., Gallo, A., Bonham, C., Ahmed, A., Melcher, M., Kim, L. H., Esquivel, C., Concepcion, W., Ayoub, W. S., Lutchman, G. A., Daugherty, T., Nguyen, M. H. 2015; 49 (2): 158-164

  Abstract

  We aimed to determine the incidence and predictors of recurrent hepatocellular carcinoma (HCC) after partial hepatectomy.Liver transplantation is the preferred treatment for selected patients with HCC, but access to donor organs is limited. Partial hepatectomy is another accepted treatment option; however, postoperative recurrence is frequently observed.This is a retrospective cohort study of 107 consecutive patients who underwent partial hepatectomy for HCC between January 1993 and February 2011 at a US University Medical Center. Study endpoints were recurrent HCC, death, loss to follow-up, or last visit without HCC.The study cohort was 78% male with a median age of 61 years and 59% Asians. A total of 50 patients developed recurrent HCC (46.7%) after a median follow-up of 12 (1 to 69) months postresection. Recurrent HCC was significantly higher in patients with left-sided resection (41% at year 1, 54% at year 2, 62% at year 3, 81% at year 4, and 90% at year 5) compared with right-sided resection (18% at year 1, 34% at year 2, 36% at year 3, 44% at year 4, and 72% at year 5). In multivariate Cox proportional hazards model also inclusive of anatomic resection and TNM stage 3/4, left-sided resection was significantly associated with increased HCC recurrence (hazard ratio, 2.13; P=0.02; 95% confidence interval, 1.08-4.2) compared with right-sided resection.HCC recurrence rate is higher among those undergoing left-sided resection: 54% at year 2 and 81% at year 4. Liver transplantation should be considered in patients who are at high risk for recurrence.

  View details for Web of Science ID 000347720300014

  View details for PubMedID 24804988

• Is Informed Consent Enough? American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Liu, W., Krawiec, K. D., Melcher, M. L. 2015

  Abstract

  As illustrated by Flechner et al (1), patients with renal failure continue to benefit from rapid innovations within multiple Kidney Paired Donation (KPD) registries. The development of the Advanced Donation Program (ADP) facilitates transplants by enabling the donors to donate even when their intended recipients (IR) are not matched yet. However, as with any innovation, ADP introduces new challenges including risks to the IRs and registries, vagueness in the definition of priority granted to the IR, and concerns about fairness to the donor should the IR become untransplantable. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/ajt.13615

  View details for PubMedID 26603607

• Factors Associated With General Surgery Residents' Desire to Leave Residency Programs A Multi-institutional Study JAMA SURGERY Gifford, E., Galante, J., Kaji, A. H., Nguyen, V., Nelson, M. T., Sidwell, R. A., Hartranft, T., Jarman, B., Melcher, M., Reeves, M., Reid, C., Jacobsen, G. R., Thompson, J., Are, C., Smith, B., Arnell, T., Hines, O. J., de Virgilio, C. 2014; 149 (9): 948-953

  View details for DOI 10.1001/jamasurg.2014.935

  View details for Web of Science ID 000342389000020

• Center-Defined Unacceptable HLA Antigens Facilitate Transplants for Sensitized Patients in a Multi-Center Kidney Exchange Program AMERICAN JOURNAL OF TRANSPLANTATION Baxter-Lowe, L. A., Cecka, M., Kamoun, M., Sinacore, J., Melcher, M. L. 2014; 14 (7): 1592-1598

  View details for DOI 10.1111/ajt.12734

  View details for Web of Science ID 000338024700019

• Quantifying the Risk of Incompatible Kidney Transplantation: A Multicenter Study AMERICAN JOURNAL OF TRANSPLANTATION Orandi, B. J., Garonzik-Wang, J. M., Massie, A. B., Zachary, A. A., Montgomery, J. R., Van Arendonk, K. J., Stegall, M. D., Jordan, S. C., Oberholzer, J., Dunn, T. B., Ratner, L. E., Kapur, S., Pelletier, R. P., Roberts, J. P., Melcher, M. L., Singh, P., Sudan, D. L., Posner, M. P., El-Amm, J. M., Shapiro, R., Cooper, M., Lipkowitz, G. S., Rees, M. A., Marsh, C. L., Sankari, B. R., Gerber, D. A., Nelson, P. W., Wellen, J., Bozorgzadeh, A., Gaber, A. O., Montgomery, R. A., Segev, D. L. 2014; 14 (7): 1573-1580

  View details for DOI 10.1111/ajt.12786

  View details for Web of Science ID 000338024700017

• PREDICT: Instituting an Educational Time Out in the Operating Room. Journal of graduate medical education Yang, R. L., Esquivel, M., Erdrich, J., Lau, J., Melcher, M. L., Wapnir, I. L. 2014; 6 (2): 382-383

  View details for DOI 10.4300/JGME-D-14-00086.1

  View details for PubMedID 24949168

• Primary Surgical Resection Versus Liver Transplantation for Transplant-Eligible Hepatocellular Carcinoma Patients DIGESTIVE DISEASES AND SCIENCES Wong, R. J., Wantuck, J., Valenzuela, A., Ahmed, A., Bonham, C., Gallo, A., Melcher, M. L., Lutchman, G., Concepcion, W., Esquivel, C., Garcia, G., Daugherty, T., Nguyen, M. H. 2014; 59 (1): 183-191

  Abstract

  Hepatocellular carcinoma (HCC) is a leading cause of mortality worldwide. Existing studies comparing outcomes after liver transplantation (LT) versus surgical resection among transplant-eligible patients are conflicting.The purpose of this study was to compare long-term survival between consecutive transplant-eligible HCC patients treated with resection versus LT.The present retrospective matched case cohort study compares long-term survival outcomes between consecutive transplant-eligible HCC patients treated with resection versus LT using intention-to-treat (ITT) and as-treated models. Resection patients were matched to LT patients by age, sex, and etiology of HCC in a 1:2 ratio.The study included 171 patients (57 resection and 114 LT). Resection patients had greater post-treatment tumor recurrence (43.9 vs. 12.9 %, p < 0.001) compared to LT patients. In the as-treated model of the pre-model for end stage liver disease (MELD) era, LT patients had significantly better 5-year survival compared to resection patients (100 vs. 69.5 %, p = 0.04), but no difference was seen in the ITT model. In the multivariate Cox proportional hazards model, inclusive of age, sex, ethnicity, tumor stage, and MELD era (pre-MELD vs. post-MELD), treatment with resection was an independent predictor of poorer survival (HR 2.72; 95 % CI, 1.08-6.86).Transplant-eligible HCC patients who received LT had significantly better survival than those treated with resection, suggesting that patients who can successfully remain on LT listing and actually undergo LT have better outcomes.

  View details for DOI 10.1007/s10620-013-2947-8

  View details for Web of Science ID 000330585500029

• Effect of the 16-Hour Work Limit on General Surgery Intern Operative Case Volume A Multi-institutional Study JAMA SURGERY Schwartz, S. I., Galante, J., Kaji, A., Dolich, M., Easter, D., Melcher, M. L., Patel, K., Reeves, M. E., Salim, A., Senagore, A. J., Takanishi, D. M., de Virgilio, C. 2013; 148 (9): 829-833

  Abstract

  IMPORTANCE The 80-hour work-week limit for all residents was instituted in 2003 and studies looking at its effect have been mixed. Since the advent of the 16-hour mandate for postgraduate year 1 residents in July 2011, no data have been published regarding the effect of this additional work-hour restriction. OBJECTIVE To determine whether the 16-hour intern work limit, implemented in July 2011, has adversely affected operative experience. DESIGN, SETTING, AND PARTICIPANTS A retrospective review of categorical postgraduate year 1 Accreditation Council for Graduate Medical Education case logs from the intern class (N = 52) (with 16-hour work limit) compared with the 4 preceding years (2007-2010; N = 197) (without 16-hour work limit). A total of 249 categorical general surgery interns from 10 general surgery residency programs in the western United States were included. MAIN OUTCOMES AND MEASURES Total, major, first-assistant, and defined-category case totals. RESULTS As compared with the preceding 4 years, the 2011-2012 interns recorded a 25.8% decrease in total operative cases (65.9 vs 88.8, P = .005), a 31.8% decrease in major cases (54.9 vs 80.5, P < .001), and a 46.3% decrease in first-assistant cases (11.1 vs 20.7, P = .008). There were statistically significant decreases in cases within the defined categories of abdomen, endocrine, head and neck, basic laparoscopy, complex laparoscopy, pediatrics, thoracic, and soft tissue/breast surgery in the 16-hour shift intern era, whereas there was no decrease in trauma, vascular, alimentary, endoscopy, liver, and pancreas cases. CONCLUSIONS AND RELEVANCE The 16-hour work limit for interns, implemented in July 2011, is associated with a significant decrease in categorical intern operative experience. If the 16-hour shift were to be extended to all postgraduate year levels, one can anticipate that additional years of training will be needed to maintain the same operative volume.

  View details for DOI 10.1001/jamasurg.2013.2677

  View details for Web of Science ID 000325212300009

  View details for PubMedID 23843028

• Kidney failure in a transplant from an identical twin. American journal of kidney diseases Lum, E. L., Morton, J. M., Melcher, M. L. 2013; 62 (2): xxi-xxiii

  View details for DOI 10.1053/j.ajkd.2013.03.046

  View details for PubMedID 23883662

• Dynamic Challenges Inhibiting Optimal Adoption of Kidney Paired Donation: Findings of a Consensus Conference AMERICAN JOURNAL OF TRANSPLANTATION Melcher, M. L., Blosser, C. D., Baxter-Lowe, L. A., Delmonico, F. L., Gentry, S. E., Leishman, R., Knoll, G. A., Leffell, M. S., Leichtman, A. B., Mast, D. A., Nickerson, P. W., Reed, E. F., Rees, M. A., Rodrigue, J. R., Segev, D. L., Serur, D., Tullius, S. G., Zavala, E. Y., Feng, S. 2013; 13 (4): 851-860

  Abstract

  While kidney paired donation (KPD) enables the utilization of living donor kidneys from healthy and willing donors incompatible with their intended recipients, the strategy poses complex challenges that have limited its adoption in United States and Canada. A consensus conference was convened March 29-30, 2012 to address the dynamic challenges and complexities of KPD that inhibit optimal implementation. Stakeholders considered donor evaluation and care, histocompatibility testing, allocation algorithms, financing, geographic challenges and implementation strategies with the goal to safely maximize KPD at every transplant center. Best practices, knowledge gaps and research goals were identified and summarized in this document.

  View details for DOI 10.1111/ajt.12140

  View details for Web of Science ID 000316911900008

  View details for PubMedID 23398969

• The Influence of Intern Home Call on Objectively Measured Perioperative Outcomes JAMA SURGERY Kastenberg, Z. J., Rhoads, K. F., Melcher, M. L., Wren, S. M. 2013; 148 (4): 347-351

  Abstract

  HYPOTHESIS In July 2011, surgical interns were prohibited from being on call from home by the new residency review committee guidelines on work hours. In support of the new Accreditation Council for Graduate Medical Education work-hour restrictions, we expected that a period of intern home call would correlate with increased rates of postoperative morbidity and mortality. DESIGN Prospective cohort. SETTING University-affiliated tertiary Veterans Affairs Medical Center. PATIENTS All patients identified in the Veterans Affairs National Surgical Quality Improvement Program database who underwent an operation performed by general, vascular, urologic, or cardiac surgery services between fiscal years (FYs) 1999 and 2010 were included. MAIN OUTCOME MEASURES During FYs 1999-2003, the first call for all patients went to an in-hospital intern. In the subsequent period (FYs 2004-2010), the first call went to an intern on home call. Thirty-day unadjusted morbidity and mortality rates and risk-adjusted observed to expected ratios were analyzed by univariate analysis and joinpoint regression, respectively. RESULTS Unadjusted overall morbidity rates decreased between 1999-2003 and 2004-2010 (12.14% to 10.19%, P =  .003). The risk-adjusted morbidity observed to expected ratios decreased at a uniform annual percentage change of -6.03% (P < .001). Unadjusted overall mortality rates also decreased between the 2 periods (1.76% to 1.26%; P =  .05). There was no significant change in the risk-adjusted mortality observed to expected ratios during the study. CONCLUSIONS The institution of an intern home call schedule was not associated with increased rates of postoperative morbidity or mortality.

  View details for DOI 10.1001/jamasurg.2013.1063

  View details for Web of Science ID 000320134900010

  View details for PubMedID 23715944

• Evaluating Deceased Donor Registries: Identifying Predictive Factors of Donor Designation AMERICAN SURGEON Hajhosseini, B., Stewart, B., Tan, J. C., Busque, S., Melcher, M. L. 2013; 79 (3): 235-241

  Abstract

  The objectives of this study were to evaluate and compare the performance of the deceased donor registries of the 50 states and the District of Columbia and to identify possible predictive factors of donor designation. Data were collected retrospectively by Donate Life America using a questionnaire sent to Donor Designation Collaborative state teams between 2007 and 2010. By the end of 2010, there were 94,669,081 designated donors nationwide. This accounted for 39.8 per cent of the U.S. population aged 18 years and over. The number of designated organ donors and registry-authorized recovered donors increased each year; however, the total number of recovered donors in 2010 was the lowest since 2004. Donor designation rate was significantly higher when license applicants were verbally questioned at the Department of Motor Vehicles (DMV) regarding their willingness to register as a donor and when DMV applicants were not given an option on DMV application forms to contribute money to support organ donation, compared with not being questioned verbally, and being offered an option to contribute money. State registries continue to increase the total number of designated organ donors; however, the current availability of organs remains insufficient to meet the demand. These data suggest that DMV applicants who are approached verbally regarding their willingness to register as a donor and not given an option on DMV application forms to contribute money to support organ donation might be more likely to designate themselves to be a donor.

  View details for Web of Science ID 000315606500003

  View details for PubMedID 23461946

• Kidney Transplant Chains Amplify Benefit of Nondirected Donors JAMA SURGERY Melcher, M. L., Veale, J. L., Javaid, B., Leeser, D. B., Davis, C. L., Hil, G., Milner, J. E. 2013; 148 (2): 165-169

  Abstract

  Despite the potential for altruistic nondirected donors (NDDs) to trigger multiple transplants through nonsimultaneous transplant chains, concerns exist that these chains siphon NDDs from the deceased donor wait list and that donors within chains might not donate after their partner receives a transplant.To determine the number of transplantations NDDs trigger through chains.Retrospective review of large, multicenter living donor-recipient database.Fifty-seven US transplant centers contributing donor-recipient pairs to the database.The NDDs initiating chain transplantation.Number of transplants per NDD.Seventy-seven NDDs enabled 373 transplantations during 46 months starting February 2008. Mean chain length initiated by NDDs was 4.8 transplants (median, 3; range, 1-30). The 40 blood type O NDDs triggered a mean chain length of 6.0 (median, 4; range, 2-30). During the interval, 66 of 77 chains were closed to the wait list, 4 of 77 were ongoing, and 7 of 77 were broken because bridge donors became unavailable. No chains were broken in the last 15 months, and every recipient whose incompatible donor donated received a kidney. One hundred thirty-three blood type O recipients were transplanted. CONCLUSION AND RELEVANCE: This large series demonstrates that NDDs trigger almost 5 transplants on average, more if the NDD is blood type O. There were more blood type O recipients than blood type O NDDs participating. The benefits of transplanting 373 patients and enabling others without living donors to advance outweigh the risk of broken chains that is decreasing with experience. Even 66 patients on the wait list without living donors underwent transplantation with living-donor grafts at the end of these chains.

  View details for Web of Science ID 000316681300011

  View details for PubMedID 23426593

• Desensitization Combined With Paired Exchange Leads to Successful Transplantation in Highly Sensitized Kidney Transplant Recipients: Strategy and Report of Five Cases TRANSPLANTATION PROCEEDINGS Yabu, J. M., Pando, M. J., Busque, S., Melcher, M. L. 2013; 45 (1): 82-87

  Abstract

  Sensitization remains a major barrier to kidney transplantation. Sensitized patients comprise 30% of the kidney transplant waiting list but fewer than 15% of highly sensitized patients are transplanted each year. Options for highly sensitized patients with an immunologically incompatible living donor include desensitization or kidney paired donation (KPD). However, these options when used alone may still not be sufficient to allow a compatible transplant for recipients who are broadly sensitized with cumulative calculated panel-reactive antibody (cPRA) > 95%. We describe in this report the combined use of both desensitization and KPD to maximize the likelihood of finding a compatible match with a more immunologically favorable donor through a kidney exchange program. This combined approach was used in five very highly sensitized patients, all with cPRA 100%, who ultimately received compatible living and deceased donor kidney transplants. We conclude that early enrollment in paired kidney donor exchange and tailored desensitization protocols are key strategies to improve care and rates of kidney transplantation in highly sensitized patients.

  View details for DOI 10.1016/j.transproceed.2012.08.007

  View details for Web of Science ID 000315007200013

• Symbiotic or Parasitic? A Review of the Literature on the Impact of Fellowships on Surgical Residents ANNALS OF SURGERY Plerhoples, T. A., Greco, R. S., Krummel, T. M., Melcher, M. L. 2012; 256 (6): 904-908

  Abstract

  We conducted a systematic review of published literature to gain a better understanding of the impact of advanced fellowships on surgical resident training and education.As fellowship opportunities rise, resident training may be adversely impacted.PubMed, MEDLINE, Scopus, BIOSIS, Web of Science, and a manual search of article bibliographies. Of the 139 citations identified through the initial electronic search and screened for possible inclusion, 23 articles were retained and accepted for this review. Data were extracted regarding surgical specialty, methodology, sample population, outcomes measured, and results.Eight studies retrospectively compared the eras before and after the introduction of a fellowship or trended data over time. Approximately half used data from a single institution, whereas the other half used some form of national data or survey. Only 3 studies used national case data. Fourteen studies looked at general surgery, 6 at obstetrics-gynecology, 2 at urology, and 1 at otolaryngology. Only one study concluded that fellowships have a generally positive impact on resident education, whereas 9 others found a negative impact. The remaining 13 studies found mixed results (n = 6) or minimal to no impact (n = 7).The overall impact of advanced surgical fellowships on surgical resident education and training remains unclear, as most studies rely on limited data of questionable generalizability. A careful study of the national database of surgery resident case logs is essential to better understand how early surgical specialization and fellowships will impact the future of general surgery education.

  View details for DOI 10.1097/SLA.0b013e318262edd5

  View details for Web of Science ID 000312261000012

  View details for PubMedID 22968071

• General Surgery Resident Remediation and Attrition A Multi-institutional Study ARCHIVES OF SURGERY Yaghoubian, A., Galante, J., Kaji, A., Reeves, M., Melcher, M., Salim, A., Dolich, M., de Virgilio, C. 2012; 147 (9): 829-833

  Abstract

  To determine the rates and predictors of remediation and attrition among general surgery residents.Eleven-year retrospective analysis of 348 categorical general surgery residents at 6 West Coast programs.Rates and predictors of remediation and attrition.Three hundred forty-eight categorical general surgery residents were included. One hundred seven residents (31%) required remediation, of which 27 were remediated more than once. Fifty-five residents (15.8%) left their programs, although only 2 were owing to failed remediation. Remediation was not a predictor of attrition (20% attrition for those remediated vs 15% who were not [P = .40]). Remediation was most frequently initiated owing to a deficiency in medical knowledge (74%). Remediation consisted of monthly meetings with faculty (79%), reading assignments (72%), required conferences (27%), therapy (12%), and repeating a clinical year (6.5%). On univariate analysis, predictors of remediation included receiving honors in the third-year surgery clerkship, United States Medical Licensing Examination (USMLE) step 1 and/or step 2, and American Board of Surgery In-Training Examination scores at postgraduate years 1 through 4. On multivariable regression analysis, remediation was associated with receiving honors in surgery (odds ratio, 1.9; P = .01) and USMLE step 1 score (odds ratio, 0.9; P = .02). On univariate analysis, the only predictor of attrition was the American Board of Surgery In-Training Examination score at the postgraduate year 3 level (P = .04).Almost one third of categorical general surgery residents required remediation during residency, which was most often owing to medical knowledge deficits. Lower USMLE step 1 scores were predictors of the need for remediation. Most remediated residents successfully completed the program. Given the high rates of remediation and the increased educational burden on clinical faculty, medical schools need to focus on better preparing students to enter surgical residency.

  View details for Web of Science ID 000308883700013

  View details for PubMedID 22987173

• Chain Transplantation: Initial Experience of a Large Multicenter Program AMERICAN JOURNAL OF TRANSPLANTATION Melcher, M. L., Leeser, D. B., Gritsch, H. A., Milner, J., Kapur, S., Busque, S., Roberts, J. P., Katznelson, S., Bry, W., Yang, H., Lu, A., Mulgaonkar, S., Danovitch, G. M., Hil, G., VEALE, J. L. 2012; 12 (9): 2429-2436

  Abstract

  We report the results of a large series of chain transplantations that were facilitated by a multicenter US database in which 57 centers pooled incompatible donor/recipient pairs. Chains, initiated by nondirected donors, were identified using a computer algorithm incorporating virtual cross-matches and potential to extend chains. The first 54 chains facilitated 272 kidney transplants (mean chain length = 5.0). Seven chains ended because potential donors became unavailable to donate after their recipient received a kidney; however, every recipient whose intended donor donated was transplanted. The remaining 47 chains were eventually closed by having the last donor donate to the waiting list. Of the 272 chain recipients 46% were ethnic minorities and 63% of grafts were shipped from other centers. The number of blood type O-patients receiving a transplant (n = 90) was greater than the number of blood type O-non-directed donors (n = 32) initiating chains. We have 1-year follow up on the first 100 transplants. The mean 1-year creatinine of the first 100 transplants from this series was 1.3 mg/dL. Chain transplantation enables many recipients with immunologically incompatible donors to be transplanted with high quality grafts.

  View details for DOI 10.1111/j.1600-6143.2012.04156.x

  View details for Web of Science ID 000307945000021

  View details for PubMedID 22812922

• Incidental kidney stones: a single center experience with kidney donor selection CLINICAL TRANSPLANTATION Kim, I. K., Tan, J. C., Lapasia, J., Elihu, A., Busque, S., Melcher, M. L. 2012; 26 (4): 558-563

  Abstract

  The presence of kidney stones has been a relative contraindication for living donation. With the widespread use of more sensitive imaging techniques as part of the routine living donor workup, kidney stones are more frequently detected, and their clinical significance in this setting is largely unknown. Records from 325 potential kidney donors who underwent MRA or CT-angiography were reviewed; 294 proceeded to donation. The prevalence of kidney stones found incidentally during donor evaluation was 7.4% (24 of 325). Sixteen donors with stones proceeded with kidney donation. All incidental calculi were nonobstructing and small (median 2 mm; range 1-9 mm). Eleven recipients were transplanted with allografts containing stones. One recipient developed symptomatic nephrolithasis after transplantation. This recipient was found to have newly formed stones secondary to hyperoxaluria, suggesting a recipient-driven propensity for stone formation. The remaining ten recipients have stable graft function, postoperative ultrasound negative for nephrolithiasis, and no sequelae from stones. No donor developed symptomatic nephrolithiasis following donation. Judicious use of allografts with small stones in donors with normal metabolic studies may be acceptable, and careful follow-up in recipients of such allografts is warranted.

  View details for DOI 10.1111/j.1399-0012.2011.01567.x

  View details for Web of Science ID 000307344400024

  View details for PubMedID 22168332

• Multiple renal arteries and non-contrast magnetic resonance angiography in transplant renal artery stenosis. Clinical kidney journal Munoz Mendoza, J., Melcher, M. L., Daniel, B., Tan, J. C. 2012; 5 (3): 272-275

  View details for DOI 10.1093/ckj/sfs027

  View details for PubMedID 26069784

• Potential Nutritional Conflicts in Bariatric and Renal Transplant Patients OBESITY SURGERY Lightner, A. L., Lau, J., Obayashi, P., Birge, K., Melcher, M. L. 2011; 21 (12): 1965-1970

  Abstract

  An increasing number of morbidly obese patients with end stage renal disease (ESRD) are sequentially undergoing bariatric surgery followed by renal transplantation. Discrepancies between the nutritional recommendations for obesity and chronic kidney disease (CKD) are often confusing for the obese patient in renal failure. However, when recommendations are structured according to stage and treatment of disease, a consistent plan can be clearly communicated to the patient. Therefore, to optimize patient and graft outcomes we present nutritional recommendations tailored to three patient populations: obese patients with ESRD, patients post Roux-en-Y gastric bypass (RYGBP) with ESRD, and patients post RYGBP and post renal transplantation.

  View details for DOI 10.1007/s11695-011-0423-0

  View details for Web of Science ID 000297201700023

  View details for PubMedID 21526378

• Cytomegalovirus in the transplanted kidney: a report of two cases and review of prophylaxis. NDT plus Anand, S., Yabu, J. M., Melcher, M. L., Kambham, N., Laszik, Z., Tan, J. C. 2011; 4 (5): 342-345

  View details for DOI 10.1093/ndtplus/sfr074

  View details for PubMedID 25984184

• Managing Finances of Shipping Living Donor Kidneys for Donor Exchanges AMERICAN JOURNAL OF TRANSPLANTATION Mast, D. A., Vaughan, W., Busque, S., VEALE, J. L., Roberts, J. P., Straube, B. M., Flores, N., Canari, C., Levy, E., Tietjen, A., Hil, G., Melcher, M. L. 2011; 11 (9): 1810-1814

  Abstract

  Kidney donor exchanges enable recipients with immunologically incompatible donors to receive compatible living donor grafts; however, the financial management of these exchanges, especially when an organ is shipped, is complex and thus has the potential to impede the broader implementation of donor exchange programs. Representatives from transplant centers that utilize the National Kidney Registry database to facilitate donor exchange transplants developed a financial model applicable to paired donor exchanges and donor chain transplants. The first tenet of the model is to eliminate financial liability to the donor. Thereafter, it accounts for the donor evaluation, donor nephrectomy hospital costs, donor nephrectomy physician fees, organ transport, donor complications and recipient inpatient services. Billing between hospitals is based on Medicare cost report defined costs rather than charges. We believe that this model complies with current federal regulations and effectively captures costs of the donor and recipient services. It could be considered as a financial paradigm for the United Network for Organ Sharing managed donor exchange program.

  View details for DOI 10.1111/j.1600-6143.2011.03690.x

  View details for Web of Science ID 000294360400009

  View details for PubMedID 21831153

• Transporting Live Donor Kidneys for Kidney Paired Donation: Initial National Results AMERICAN JOURNAL OF TRANSPLANTATION Segev, D. L., VEALE, J. L., Berger, J. C., Hiller, J. M., Hanto, R. L., Leeser, D. B., GEFFNER, S. R., Shenoy, S., BRY, W. I., Katznelson, S., Melcher, M. L., Rees, M. A., Samara, E. N., Israni, A. K., Cooper, M., Montgomery, R. J., Malinzak, L., Whiting, J., Baran, D., Tchervenkov, J. I., Roberts, J. P., Rogers, J., Axelrod, D. A., Simpkins, C. E., Montgomery, R. A. 2011; 11 (2): 356-360

  Abstract

  Optimizing the possibilities for kidney-paired donation (KPD) requires the participation of donor-recipient pairs from wide geographic regions. Initially it was envisaged that donors would travel to the recipient center; however, to minimize barriers to participation and simplify logistics, recent trends have involved transporting the kidneys rather than the donors. The goal of this study was to review outcomes of this practice. KPD programs throughout the United States were directly queried about all transplants involving live donor kidney transport. Early graft function was assessed by urine output in the first 8 h, postoperative serum creatinine trend, and incidence of delayed graft function. Between April 27, 2007 and April 29, 2010, 56 live donor kidneys were transported among 30 transplant centers. Median CIT was 7.2 h (IQR 5.5-9.7, range 2.5-14.5). Early urine output was robust (>100 cc/h) in all but four patients. Creatinine nadir was <2.0 mg/dL in all (including the four with lower urine output) but one patient, occurring at a median of 3 days (IQR 2-5, range 1-49). No patients experienced delayed graft function as defined by the need for dialysis in the first week. Current evidence suggests that live donor kidney transport is safe and feasible.

  View details for DOI 10.1111/j.1600-6143.2010.03386.x

  View details for Web of Science ID 000286626700023

  View details for PubMedID 21272238

• Sclerosing Peritonitis After Kidney Transplantation: A Not-So-Silky Cocoon DIGESTIVE DISEASES AND SCIENCES Morrow, E. H., Gallo, A. E., Melcher, M. L. 2011; 56 (2): 307-310

  View details for DOI 10.1007/s10620-010-1471-3

  View details for Web of Science ID 000286664900007

  View details for PubMedID 21063775

• Donors with Kidney Stones: Should We Pass? Kim, I. K., Lapasia, J., Elihu, A., Tan, J., Scandling, J., Busque, S., Melcher, M. WILEY-BLACKWELL PUBLISHING, INC. 2011: 66-66

  View details for Web of Science ID 000286406500042

• Cytomegalovirus in the transplanted kidney: a report of two cases and review of prophylaxis Nephrology Dialysis Transplantation Anand S, Yabu JM, Melcher ML, Kambham N, Laszik Z, Tan JC. 2011; 4 (5): 342-345
• Population Pharmacokinetic Analysis of Mycophenolic Acid Coadministered With Either Tasocitinib (CP-690,550) or Tacrolimus in Adult Renal Allograft Recipients THERAPEUTIC DRUG MONITORING Lamba, M., Tafti, B., Melcher, M., Chan, G., Krishnaswami, S., Busque, S. 2010; 32 (6): 778-781

  Abstract

  Tasocitinib (CP-690,550) is an orally active Janus kinase inhibitor that is in development for prophylaxis of acute rejection after kidney transplantation and for the treatment of select autoimmune diseases. The current study was conducted to evaluate the systemic exposure of mycophenolic acid (MPA) in de novo kidney transplant patients when coadministered with tasocitinib compared with exposure in patients receiving tacrolimus, which has no effect on MPA pharmacokinetics. Plasma MPA concentrations were obtained from 17 adult patients who received either 15 mg or 30 mg tasocitinib twice daily (eight patients) or tacrolimus (nine patients) after kidney transplantation. All patients also received concomitant mycophenolate mofetil, prednisone, and basiliximab induction. The median mycophenolate mofetil dose was 1000 mg twice daily. A two-compartment population pharmacokinetic model estimating oral clearance, between-patient variability in oral clearance, central volume of distribution, and residual variability in combination with historical estimates of first-order absorption rate constant, intercompartmental clearance, and peripheral volume of distribution adequately described the sparse MPA data. Based on individual estimates oral clearance from the population pharmacokinetic model, mean steady-state area under the concentration-time curve values for a mycophenolate mofetil dose of 1000 mg twice daily were 63 mg·hr/L (22%) and 59 mg·hr/L (36%) for the tasocitinib and tacrolimus groups, respectively. These results indicate that tasocitinib does not influence systemic MPA exposure.

  View details for DOI 10.1097/FTD.0b013e3181f361c9

  View details for Web of Science ID 000284103400017

  View details for PubMedID 20926996

• Outcomes of surgical repair of bile leaks and strictures after adult-to-adult living donor liver transplant CLINICAL TRANSPLANTATION Melcher, M. L., Freise, C. E., Ascher, N. L., Roberts, J. P. 2010; 24 (6): E230-E235

  Abstract

  We sought to determine factors that predict the successful surgical repair of biliary complications after adult living donor liver transplantation (ALDLT).Records of 82 consecutive ALDLT right lobe recipients were reviewed. Operations were performed on 19 recipients for biliary complications. Post-operative biliary complications were analyzed. Fisher's exact test was used to identify variables that correlated with successful surgical repair.A total of 29 recipients had biliary complications, of which 19 had a surgical repair. The five recipients, operated on for a stricture without history of leaks, did not develop further complications. However, nine of 14 with a history of a leak developed further complications after surgical repair (p-value = 0.044). All five who presented with a biliary complication more than 100 d after transplant had successful surgical repair; however, nine out of 13 who presented within 57 d had additional complications after repair.Operations for strictures after ALDLT are more successful than operations for leaks. Recipients with isolated biliary strictures after ALDLT can be managed surgically; however, recipients with history of a leak often require additional interventions after surgical repair.

  View details for DOI 10.1111/j.1399-0012.2010.01289.x

  View details for Web of Science ID 000284894800004

  View details for PubMedID 20529098

• Comparison of biliary complications in adult living-donor liver transplants performed at two busy transplant centers CLINICAL TRANSPLANTATION Melcher, M. L., Pomposelli, J. J., Verbesey, J. E., McTaggart, R. A., Freise, C. E., Ascher, N. L., Roberts, J. P., Pomfret, E. A. 2010; 24 (5): E137-E144

  Abstract

  Adult living-donor liver transplantation (ALDLT) has a high rate of biliary complications. We identified risk factors that correlate with biliary leaks and strictures by combining data from two centers. Records of ALDLT right lobe recipients (n = 156) at two centers between December 1998 and February 2005 were reviewed. Leak rate was analyzed in 144 recipients after we excluded those with hepatic artery thrombosis or death within 30 d of transplant. Stricture rate was also analyzed in 132 recipients after we excluded those with graft survival or follow-up <180 d. Biliary reconstructions were performed using either duct-to-duct (DD) or Roux-en-Y hepaticojejunostomy and were subclassified by anatomic type, number of anastomoses performed, and stent use. Prevalence of a leak and/or a stricture was 39%; 11% of recipients developed both. Single DD anastomoses between the graft right hepatic duct to the recipient common duct had significantly lower incidence of leaks compared to all other anastomotic types. Early leak was predictive of late stricture development (p = 0.006), but recipient demographics, diagnosis, warm ischemia time, anastomosis type, duct number, year of transplant, stent use, and transplant center were not. The results suggest donors with a single right hepatic duct reconstructed to the recipient common bile duct are the most likely to avoid biliary problems after ALDLT.

  View details for DOI 10.1111/j.1399-0012.2009.01189.x

  View details for Web of Science ID 000282570300002

  View details for PubMedID 20047615

• Predicting Performance on the American Board of Surgery Qualifying and Certifying Examinations A Multi-institutional Study ARCHIVES OF SURGERY de Virgilio, C., Yaghoubian, A., Kaji, A., Collins, J. C., Deveney, K., Dolich, M., Easter, D., Hines, O. J., Katz, S., Liu, T., Mahmoud, A., Melcher, M. L., Parks, S., Reeves, M., Salim, A., Scherer, L., Takanishi, D., Waxman, K. 2010; 145 (9): 852-856

  Abstract

  We sought to determine whether US Medical Licensing Examination (USMLE) Step 1 score, American Board of Surgery (ABS) In-Training Examination (ABSITE) score, and other variables are associated with failing the ABS qualifying and certifying examinations. Identifying such factors may assist in the early implementation of an academic intervention for at-risk residents.Retrospective review.Seventeen general surgery training programs in the western United States.Six hundred seven residents who graduated in 2000-2007.First-time pass rates on the qualifying and certifying examinations, US vs non-US medical school graduation, USMLE Steps 1 and 2 scores, ABSITE scores, operative case volume, fellowship training, residency program type, and mandatory research.The first-time qualifying and certifying examination pass rates for the 607 graduating residents were 78% and 74%, respectively. On multivariable analysis, scoring below the 35th percentile on the ABSITE at any time during residency was associated with an increased risk of failing both examinations (odds ratio, 0.23 [95% confidence interval, 0.08-0.68] for the qualifying examination and 0.35 [0.20-0.61] for the certifying examination), as was scoring less than 200 on the USMLE Step 1 (0.36 [0.21-0.62] for the qualifying examination and 0.62 [0.42-0.93] for the certifying examination). A mandatory research year was associated with an increased likelihood of passing the certifying examination (odds ratio, 3.3 [95% confidence interval, 1.6-6.8]).Residents who are more likely to fail the ABS qualifying and certifying examinations can be identified by a low USMLE Step 1 score and by poor performance on the ABSITE at any time during residency. These findings support the use of the USMLE Step 1 score in the surgical residency selection process and a formal academic intervention for residents who perform poorly on the ABSITE.

  View details for Web of Science ID 000281764400010

  View details for PubMedID 20855755

• Asynchronous, Out-of-Sequence, Transcontinental Chain Kidney Transplantation: A Novel Concept AMERICAN JOURNAL OF TRANSPLANTATION Butt, F. K., Gritsch, H. A., Schulam, P., Danovitch, G. M., Wilkinson, A., Del Pizzo, J., Kapur, S., Serur, D., Katznelson, S., Busque, S., Melcher, M. L., McGuire, S., Charlton, M., Hil, G., Veale, J. L. 2009; 9 (9): 2180-2185

  Abstract

  The organ donor shortage has been the most important hindrance in getting listed patients transplanted. Living kidney donors who are incompatible with their intended recipients are an untapped resource for expanding the donor pool through participation in transplant exchanges. Chain transplantation takes this concept further, with the potential to benefit even more recipients. We describe the first asynchronous, out of sequence transplant chain that was initiated by transcontinental shipment of an altruistic donor kidney 1 week after that recipient's incompatible donor had already donated his kidney to the next recipient in the chain. The altruistic donor kidney was transported from New York to Los Angeles and functioned immediately after transplantation. Our modified-sequence asynchronous transplant chain (MATCH) enabled eight recipients, at four different institutions, to benefit from the generosity of one altruistic donor and warrants further exploration as a promising step toward addressing the organ donor shortage.

  View details for DOI 10.1111/j.1600-6143.2009.02730.x

  View details for Web of Science ID 000269180500027

  View details for PubMedID 19563335

• Recovery of Renal Function in a Dialysis-Dependent Patient Following Gastric Bypass Surgery OBESITY SURGERY Tafti, B. A., Haghdoost, M., ALVAREZ, L., Curet, M., Melcher, M. L. 2009; 19 (9): 1335-1339

  Abstract

  There is increasing evidence that obesity, independently from other comorbidities such as diabetes and hypertension, can cause renal dysfunction. While this indolent dysfunction may be asymptomatic, it can render patients more susceptible to renal insufficiency when the kidneys are further injured by other pathological processes. Here, we present a morbidly obese patient whose type-A aortic dissection was complicated by acute renal failure that subsequently progressed into end-stage renal disease. However, his renal function improved dramatically following substantial weight reduction after gastric bypass surgery obviating the need for dialysis and transplantation. The potential mechanisms by which a patient's obesity may lead to renal dysfunction are discussed. This case and other similar reports suggest that obese patients with renal failure can safely undergo bariatric surgery and that bariatric surgery may have a role in treating chronic kidney disease in select morbidly obese patients.

  View details for DOI 10.1007/s11695-009-9907-6

  View details for Web of Science ID 000269153200022

  View details for PubMedID 19693639

• Postoperative infectious complications of abdominal solid organ transplantation. Journal of intensive care medicine Hlava, N., Niemann, C. U., Gropper, M. A., Melcher, M. L. 2009; 24 (1): 3-17

  Abstract

  There is a rapidly growing population of immunocompromised organ transplant recipients. These patients are at risk of a large variety of infections that have significant consequences on mortality, graft dysfunction, and graft loss. The diagnosis and treatment of these infections are facilitated by an understanding of the preoperative, perioperative, and postoperative risk factors; the typical pathogens; and their characteristic time of presentation. On the basis of these factors, we put forth an algorithm for diagnosing and treating suspected infections in solid organ transplant recipients.

  View details for DOI 10.1177/0885066608327127

  View details for PubMedID 19017663

• "Something Special in the Air": Transcontinental Shipments of Living Donor Kidneys for Transplantation. Veale, J. L., Butt, F. K., Gritsch, H. A., Danovitch, G., Wilkinson, A., Schulam, P., Del Pizzo, J., Kapur, S., Leeser, D., Serur, D., Katznelson, S., Busque, S., Melcher, M. L., McGuire, S., Charlton, M., Hil, G., Cecka, J. M. WILEY-BLACKWELL. 2009: 435-435

  View details for Web of Science ID 000265068800855

• Overcoming Immunological Barriers to Living Donor Kidney Transplantation At Stanford University Medical Center SGH Proceedings Ladner DP, Busque S, Melcher ML 2008; 17 (1): 5-19
• Thymoglobulin-associated Cd4+ T-cell depletion and infection risk in HIV-infected renal transplant recipients AMERICAN JOURNAL OF TRANSPLANTATION Carter, J. T., Melcher, M. L., Carlson, L. L., Roland, M. E., Stock, P. G. 2006; 6 (4): 753-760

  Abstract

  HIV-infected patients are increasingly referred for kidney transplantation, and may be at an increased risk for rejection. Treatment for rejection frequently includes thymoglobulin. We studied thymoglobulin's effect on CD4+ T-cell count, risk of infection and rejection reversal in 20 consecutive HIV-infected kidney recipients. All patients used antiretroviral therapy and opportunistic infection prophylaxis. Maintenance immunosuppression consisted of prednisone, mycophenolate mofetil and cyclosporine. Eleven patients received thymoglobulin (7 for rejection and 4 for delayed/slow graft function) while 9 did not. These two groups were similar in age, gender, race, donor characteristics and immunosuppression. Mean CD4+ T-cell counts remained stable in patients who did not receive thymoglobulin, but became profoundly suppressed in those who did, decreasing from 475 +/- 192 to 9 +/- 10 cells/microL (p < 0.001). Recovery time ranged from 3 weeks to 2 years despite effective HIV suppression. Although opportunistic infections were successfully suppressed, low CD4+ T-cell count was associated with increased risk of serious infections requiring hospitalization. Rejection reversed in 6 of 7 patients receiving thymoglobulin. We conclude that thymoglobulin reverses acute rejection in HIV-infected kidney recipients, but produces profound and long-lasting suppression of the CD4+ T-cell count associated with increased risk of infections requiring hospitalization.

  View details for DOI 10.1111/j.1600-6143.2006.01238.x

  View details for Web of Science ID 000235839900015

  View details for PubMedID 16539632

• Antibody-mediated rejection of a pancreas allograft AMERICAN JOURNAL OF TRANSPLANTATION Melcher, M. L., Olson, J. L., Baxter-Lowe, L. A., Stock, P. G., Posselt, A. M. 2006; 6 (2): 423-428

  Abstract

  The role of antibody-mediated rejection (AMR) in pancreas transplantation is poorly understood. Here, we report on a patient who developed AMR of his pancreas allograft after receiving a simultaneous pancreas-kidney transplant. Pre-operative enhanced cytotoxicity and flow cytometry T-cell crossmatches were negative; B-cell crossmatches were not performed as per institutional protocol. The patient's post-operative course was significant for elevated serum amylase levels and development of hyperglycemia approximately 1 month after transplantation. A pancreatic biopsy at this time showed no cellular infiltrate but strong immunofluorescent staining for C4d in the interacinar capillaries. Analysis of the patient's serum identified donor-specific HLA-DR alloantibodies. He received intravenous immunoglobulin (IVIg), rituximab and plasmapheresis, and his pancreatic function normalized. We conclude that clinically significant AMR can develop in a pancreas allograft and recommend that pancreatic biopsies be assessed for C4d deposition if the patient has risk factors for AMR and/or the pathologic evidence for cell-mediated rejection is underwhelming.

  View details for DOI 10.1111/j.1600-6143.2005.01185.x

  View details for Web of Science ID 000234735200025

  View details for PubMedID 16426331

• Spontaneous splenic rupture: The masquerade of minor trauma JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE Tataria, M., Dicker, R. A., Melcher, M., Spain, D. A., Brundage, S. I. 2005; 59 (5): 1228-1230

  View details for DOI 10.1097/01.ta.0000196439.77828.9d

  View details for Web of Science ID 000234514000043

  View details for PubMedID 16385305

• More than 500 consecutive laparoscopic donor nephrectomies without conversion or repeated surgery ARCHIVES OF SURGERY Melcher, M. L., Carter, J. T., Posselt, A., Duh, Q. Y., Stoller, M., Freise, C. E., Kang, S. M. 2005; 140 (9): 835-839

  Abstract

  Concern exists as to the safety of laparoscopic donor nephrectomy (LDN) compared with open donor nephrectomy. Reported complications of LDN include emergent conversion to an open procedure, repeated surgery for postoperative bleeding, and even death. We hypothesize that LDNs can be performed safely, with a complication rate comparable with that of open donor nephrectomies.Case series and review of the literature.Tertiary care university hospital.Five hundred thirty kidney donors.An LDN performed without hand assistance, with the kidney extracted through a low transverse incision.Mean operative time, requirement for transfusion, intraoperative complications, and postoperative complications.This series includes 84 right-sided donor nephrectomies, 86 donors with a body mass index greater than 30 (calculated as weight in kilograms divided by the square of height in meters), and 91 donors with complex vascular anatomy. Mean donor age was 40 years (range, 18-73 years), and mean +/- SD operative time was 196 +/- 43 minutes. The only conversion occurred early in the series, and there have been 525 subsequent cases without the need for conversion or repeated surgery. There were no donor deaths. Five donors (0.9%) required perioperative blood transfusions. Overall complication rate was 6.4%, including 14 minor wound infections, 2 bowel injuries, 1 case of prolonged ileus, 3 splenic injuries, 2 bladder infections, 1 bladder injury, 1 case of rhabdomyolysis, 1 case of pneumonia, and 2 thromboembolic events.This series demonstrates that LDN can be performed at least as safely as open donor nephrectomy, with minimal bleeding and few postoperative complications.

  View details for Web of Science ID 000231641400004

  View details for PubMedID 16172291

• Gastric carcinoid tumors in multiple endocrine neoplasia-1 patients with Zollinger-Ellison syndrome can be symptomatic, demonstrate aggressive growth, and require surgical treatment SURGERY NORTON, J. A., Melcher, M. L., Gibril, F., Jensen, R. T. 2004; 136 (6): 1267-1273

  Abstract

  Gastric carcinoid tumors occur in 15% to 50% of patients with multiple endocrine neoplasia-1/Zollinger-Ellison syndrome (MEN-1/ZES) but are thought to be benign. We report 5 patients with MEN-1/ZES with symptomatic, aggressive gastric carcinoid tumors that required surgical procedures.This was a retrospective chart review.Each patient had MEN-1/ZES. Each patient had innumerable gastric carcinoid tumors with symptoms. The fasting gastrin level was 47,000 pg/mL (normal, <200 pg/mL); the basal acid output was 79 mEq/hr (n = 3), and the age at surgical exploration was 47 +/- 6 years, with a duration of MEN-1 of 21 +/- 3 years and of ZES of 15 +/- 2 years. All patients had elevated 5-HIAA or serotonin levels. Somatostatin receptor scintigraphy showed increased stomach uptake in 4 patients (80%). Four patients had a total gastrectomy; 4 patients had lymph node metastases removed, and 3 patients had liver metastases resected. One patient who did not have a total gastrectomy had liver carcinoid metastases.These results demonstrate that gastric carcinoid tumors in patients with longstanding MEN-1/ZES may be symptomatic, aggressive, and metastasize to the liver. With increased long-term medical treatment and life expectancy, these tumors will become an important determinant of survival.

  View details for DOI 10.1016/j.surg.2004.06.057

  View details for Web of Science ID 000225874800046

  View details for PubMedID 15657586

• A novel technique to treat ruptured umbilical hernias in patients with liver cirrhosis and severe ascites JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES-PART A Melcher, M. L., Lobato, R. L., Wren, S. M. 2003; 13 (5): 331-332

  Abstract

  The full-thickness skin erosion (rupture) of an umbilical hernia in a patient with end-stage liver disease can lead to significant morbidity and mortality. Here, we present a case report of the use of a novel technique to treat a patient with this condition. The use of a fibrin-based tissue adhesive provides a means of managing such patients medically.

  View details for Web of Science ID 000185762400011

  View details for PubMedID 14617394

• Ileocolic intussusception in an adult JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Melcher, M. L., Safadi, B. 2003; 197 (3): 518-518

  View details for DOI 10.1016/S1072-7515(03)00589-1

  View details for Web of Science ID 000185124800025

  View details for PubMedID 12946809

• Identification and characterization of the CLK1 gene product, a novel CaM kinase-like protein kinase from the yeast Saccharomyces cerevisiae JOURNAL OF BIOLOGICAL CHEMISTRY Melcher, M. L., Thorner, J. 1996; 271 (47): 29958-29968

  Abstract

  The CLK1 gene of Saccharomyces cerevisiae encodes a 610-residue protein kinase that resembles known type II Ca2+/calmodulin-dependent protein kinases (CaM kinases), including the CMK1 and CMK2 gene products from the same yeast. The Clk1 kinase domain is preceded by a 162-residue N-terminal extension, followed by a 132-residue C-terminal extension (which contains a basic segment resembling known calmodulin-binding sites) and is as similar to mammalian CaM kinase (38% identity to rat CaM kinase alpha) as it is to yeast CaM kinase (37% identity to Cmk2). However, Clk1 shares 52% identity with Rck1, another putative protein kinase encoded in the S. cerevisiae genome. Clk1 tagged with a c-myc epitope (expressed in yeast) and a GST-Clk1 fusion (expressed in bacteria) underwent autophosphorylation and phosphorylated an exogenous substrate (yeast protein synthesis elongation factor 2), primarily on Ser. Neither Clk1 activity was stimulated by purified yeast calmodulin (CMD1 gene product), with or without Ca2+; no association of Clk1 with Cmd1 was detectable by other methods. C-terminally truncated Clk1(Delta487-610) was growth-inhibitory when overexpressed, whereas catalytically inactive Clk1(K201R Delta487-610) was not, suggesting that the C terminus is a negative regulatory domain. Using immunofluorescence, Clk1 was localized to the cytosol and excluded from the nucleus. A clk1Delta mutant, a clk1Delta rck1Delta double mutant, a clk1Delta cmk1Delta cmk2Delta triple mutant, and a clk1Delta rck1Delta cmk1Delta cmk2Delta quadruple mutant were all viable and manifested no other overt growth phenotype.

  View details for Web of Science ID A1996VU52500069

  View details for PubMedID 8939941