Complement Blockade in Recipients Prevents Delayed Graft Function and Delays Antibody-mediated Rejection in a Nonhuman Primate Model of Kidney Transplantation.

BACKGROUND: Complement activation in kidney transplantation is implicated in the pathogenesis of delayed graft function (DGF). This study evaluated the therapeutic efficacy of high-dose recombinant human C1 esterase inhibitor (rhC1INH) to prevent DGF in a nonhuman primate model of kidney transplantation after brain death and prolonged cold ischemia. METHODS: Brain death donors underwent 20 h of conventional management. Procured kidneys were stored on ice for 44-48 h, then transplanted into ABO-compatible major histocompatibility complex-mismatched recipients. Recipients were treated with vehicle (n = 5) or rhC1INH 500 U/kg plus heparin 40 U/kg (n = 8) before reperfusion, 12 h, and 24 h posttransplant. Recipients were followed up for 120 d. RESULTS: Of vehicle-treated recipients, 80% (4 of 5) developed DGF versus 12.5% (1 of 8) rhC1INH-treated recipients (P = 0.015). rhC1INH-treated recipients had faster creatinine recovery, superior urinary output, and reduced urinary neutrophil gelatinase-associated lipocalin and tissue inhibitor of metalloproteinases 2-insulin-like growth factor-binding protein 7 throughout the first week, indicating reduced allograft injury. Treated recipients presented lower postreperfusion plasma interleukin (IL)-6, IL-8, tumor necrosis factor-alpha, and IL-18, lower day 4 monocyte chemoattractant protein 1, and trended toward lower C5. Treated recipients exhibited less C3b/C5b-9 deposition on day 7 biopsies. rhC1INH-treated animals also trended toward prolonged mediated rejection-free survival. CONCLUSIONS: Our results recommend high-dose C1INH complement blockade in transplant recipients as an effective strategy to reduce kidney injury and inflammation, prevent DGF, delay antibody-mediated rejection development, and improve transplant outcomes.

Kidney After Liver Transplantation Matched-pair Analysis: Are Kidneys Allocated to Appropriate Patients to Maximize Their Survival?

BACKGROUND: Kidney after liver transplantation (KALT) is the best therapeutic option for patients with end-stage renal disease after orthotopic liver transplantation (OLT). New allocation policies prioritize kidneys to patients in renal failure within the first year following OLT. There is little data on how kidney quality, measured by kidney donor profile index (KDPI), impacts KALT survival outcomes. METHODS: The United Network for Organ Sharing database was queried for adult KALT recipients from 1988 to 2015 and compared to their paired kidney transplant alone (KTA) recipients. Seven hundred forty-five pairs were stratified into 3 KDPI subgroups and compared patient survival, graft survival, and death-censored graft survival among matched-paired recipients. RESULTS: Overall, KTA recipients had superior patient and graft survival compared with the KALT group. KTA patient survival was superior for all 3 KDPI subgroups analysis. KTA graft survival was superior compared with KALT recipients of KDPI 21%-85% kidneys. Inferior graft half-life was observed in KALT versus KTA recipients with KDPI 21%-85% and >85%. CONCLUSIONS: From a utilitarian perspective, it is important that kidneys are allocated to recipients that are able to maximize their benefit from the full life of the organ. In KTA recipients, graft quality correlates directly to graft survival. However, in KALT patients receiving the matched-pair kidneys of the KTA recipients, patient mortality, rather than kidney quality, dictates graft survival significantly. As allocation practices continue developing, utilization of expanded criteria kidneys that better match anticipated patient and graft survival should be strongly considered to maximize the benefits of limited resources for the greatest number of patients.

The Role of PhD Faculty in Advancing Research in Departments of Surgery.

OBJECTIVE: To determine the academic contribution as measured by number of publications, citations, and National Institutes of Health (NIH) funding from PhD scientists in US departments of surgery. SUMMARY BACKGROUND DATA: The number of PhD faculty working in US medical school clinical departments now exceeds the number working in basic science departments. The academic impact of PhDs in surgery has not been previously evaluated. METHODS: Academic metrics for 3850 faculties at the top 55 NIH-funded university and hospital-based departments of surgery were collected using NIH RePORTER, Scopus, and departmental websites. RESULTS: MD/PhDs and PhDs had significantly higher numbers of publications and citations than MDs, regardless of academic or institutional rank. PhDs had the greatest proportion of NIH funding compared to both MDs and MD/PhDs. Across all academic ranks, 50.2% of PhDs had received NIH funding compared with 15.2% of MDs and 33.9% of MD/PhDs (P < 0.001). The proportion of PhDs with NIH funding in the top 10 departments did not differ from those working in departments ranked 11 to 50 (P = 0.456). A greater percentage of departmental PhD faculty was associated with increased rates of MD funding. CONCLUSIONS: The presence of dedicated research faculty with PhDs supports the academic mission of surgery departments by increasing both NIH funding and scholarly productivity. In contrast to MDs and MD/PhDs, PhDs seem to have similar levels of academic output and funding independent of the overall NIH funding environment of their department. This suggests that research programs in departments with limited resources may be enhanced by the recruitment of PhD faculty.

Is there an impending loss of academically productive trauma surgical faculty? An analysis of 4,015 faculty.

OBJECTIVE: The aim of this work was to compare the academic impact of trauma surgery faculty relative to faculty in general surgery and other surgery subspecialties. METHODS: Scholarly metrics were determined for 4,015 faculty at the top 50 National Institutes of Health (NIH)-funded university-based departments and five hospital-based surgery departments. RESULTS: Overall, 317 trauma surgical faculty (8.2%) were identified. This compared to 703 other general surgical faculty (18.2%) and 2,830 other subspecialty surgical faculty (73.5%). The average size of the trauma surgical division was six faculty. Overall, 43% were assistant professors, 29% were associate professors, and 28% were full professors, while 3.1% had PhD, 2.5% had MD and PhD, and, 16.3% were division chiefs/directors. Compared with general surgery, there were no differences regarding faculty academic levels or leadership positions. Other surgical specialties had more full professors (39% vs. 28%; p < 0.05) and faculty with research degrees (PhD, 7.7%; and MD and PhD, 5.7%). Median publications/citations were lower, especially for junior trauma surgical faculty (T) compared with general surgery (G) and other (O) surgical specialties: assistant professors (T, 9 publications/76 citations vs. G, 13/138, and O, 18/241; p < 0.05), associate professors (T, 22/351 vs. G, 36/700, and O, 47/846; p < 0.05), and professors (T, 88/2,234 vs. G, 93/2193; p = NS [not significant for either publications/citations] and O, 99/2425; p = NS). Publications/Citations for division chiefs/directors were comparable with other specialties: T, 77/1,595 vs. G, 103/2,081 and O, 74/1,738; p = NS, but were lower for all nonchief faculty; T, 23/368 vs. G, 30/528 and O, 37/658; p < 0.05. Trauma surgical faculty were less likely to have current or former NIH funding than other surgical specialties (17 % vs. 27%; p < 0.05), and this included a lower rate of R01/U01/P01 funding (5.5% vs. 10.8%; p < 0.05). CONCLUSIONS: Senior trauma surgical faculty are as academically productive as other general surgical faculty and other surgical specialists. Junior trauma faculty, however, publish at a lower rate than other general surgery or subspecialty faculty. Causes of decreased academic productivity and lower NIH funding must be identified, understood, and addressed.

Determining the Drivers of Academic Success in Surgery: An Analysis of 3,850 Faculty.

OBJECTIVE: Determine drivers of academic productivity within U.S. departments of surgery. METHODS: Eighty academic metrics for 3,850 faculty at the top 50 NIH-funded university- and 5 outstanding hospital-based surgical departments were collected using websites, Scopus, and NIH RePORTER. RESULTS: Mean faculty size was 76. Overall, there were 35.3% assistant, 27.8% associate, and 36.9% full professors. Women comprised 21.8%; 4.9% were MD-PhDs and 6.1% PhDs. By faculty-rank, median publications/citations were: assistant, 14/175, associate, 39/649 and full-professor, 97/2250. General surgery divisions contributed the most publications and citations. Highest performing sub-specialties per faculty member were: research (58/1683), transplantation (51/1067), oncology (41/777), and cardiothoracic surgery (48/860). Overall, 23.5% of faculty were principal investigators for a current or former NIH grant, 9.5% for a current or former R01/U01/P01. The 10 most cited faculty (MCF) within each department contributed to 42% of all publications and 55% of all citations. MCF were most commonly general (25%), oncology (19%), or transplant surgeons (15%). Fifty-one-percent of MCF had current/former NIH funding, compared with 20% of the rest (p<0.05); funding rates for R01/U01/P01 grants was 25.1% vs. 6.8% (p<0.05). Rate of current-NIH MCF funding correlated with higher total departmental NIH rank (p < 0.05). CONCLUSIONS: Departmental academic productivity as defined by citations and NIH funding is highly driven by sections or divisions of research, general and transplantation surgery. MCF, regardless of subspecialty, contribute disproportionally to major grants and publications. Approaches that attract, develop, and retain funded MCF may be associated with dramatic increases in total departmental citations and NIH-funding.