Risk Factors for End‐Stage Kidney Disease After Pediatric Liver Transplantation

Adult liver transplant (LT) recipients commonly develop advanced kidney disease. However, burden of end‐stage kidney disease (ESKD) after pediatric LT has not been well‐described. We performed a retrospective cohort study of pediatric LTs in the United States from 1990 to 2010. Multivariable Cox regression models were fit to determine risk factors for ESKD and death. Eight thousand nine hundred seventy six children received LTs. During median follow‐up of 7.8 years, 2005 (22%) subjects died (mortality rate 26.1 cases/1000 person‐years); 167 (2%) developed ESKD (incidence rate 2.2 cases/1000 person‐years). Risk factors for ESKD included older age at LT (highest risk age >15 vs. < 5 years, HR = 4.94, p < 0.001), hepatitis C (HR 2.79, p = 0.004), liver re‐transplant (HR 2.67, p < 0.001), eGFR pre‐LT < 60 versus ≥ 60 (HR 2.37, p < 0.001), hepatitis B (HR 2.25, p = 0.027), black race (HR 1.46, p = 0.046), and male sex (HR 1.44, p = 0.022). LT recipients with ESKD had increased risk of mortality (HR 2.37, p < 0.001). Among pediatric LT recipients, rate of ESKD was lower than among adults and far exceeded by rate of death, however follow‐up time in this study may underestimate lifetime burden of ESKD. Although uncommon, ESKD was highly associated with mortality. Pediatric LT recipients should be routinely monitored for kidney disease, particularly those at highest risk of ESKD.     

Industry payments to spine surgeons from 2014 to 2019: trends and comparison of payments to spine surgeons versus all physicians

BACKGROUND CONTEXTThe ethics of industry payments to physicians and the potential impact on healthcare costs and research outcomes have long been topics of debate. Industry payments to spine surgeons are frequently scrutinized. Transparency of industry relationships with physicians provides insight into their possible impact on clinical decision-making and utilization of care.PURPOSE: To analyze trends in medical industry payments to spine surgeons and all physicians from 2014 to 2019, and further evaluate whether specific payments to spine surgeons vary based on company size.STUDY DESIGN/SETTINGCross-sectional investigation of publicly reported Center for Medicare and Medicaid Services (CMS) Open Payments Database (OPD)POPULATION SAMPLEAll US providers listed as receiving industry payments with further evaluation of payments to neurosurgeons and orthopedic spine surgeons.OUTCOME MEASURESMain measures were the magnitude and trends of industry general and research payments and subcategories of general payments, such as royalty/license and consulting fees, to spine surgeons and comparison to all physicians over the six-year period. Variations in payment patterns among spine device manufacturers with the highest reported level of spine surgeon payments in 2019.METHODSFrom 2014 to 2019 publicly reported general and research industry payments in the CMS OPD were analyzed. Trends in payments to all physicians were compared to trends in payments to neurosurgeons and orthopedic spine surgeons. Trends in payment patterns among spine device manufacturers with the highest payments in 2019 were determined. Linear regression analysis was completed to find statistically significant outcomes.RESULTSOur investigation found an aggregate of $42,710,365,196 general and research payments reported to all physicians over the 6-year period, 2.6% ($1,112,936,203) of which went to spine surgeons. Industry general and research payments to spine surgeons decreased by 17.5% ($195,571,109, 2014; $161,283,683, 2019), while increasing by 8.7% ($6,706,208,391, 2014; $7,288,003,832, 2019) to all physicians. Industry research payments to spine surgeons were notably low each year and decreased to only 0.5% of research payments made to all physicians in 2019. Median payment received by spine surgeons as well as the overall distribution of payments to the 75th and 95th percentile significantly increased over the six-year period in comparison to the stable distribution of payments to all physicians. Top eight spine device manufactures with the highest level of spine surgeon payments accounted for 72.9% payments in 2014 but decreased payments by 17.6% to 2019 ($120,409,083.75, 2014; $99,283,264.49, 2019).CONCLUSIONSIndustry general and research payments to all physicians increased from 2014 to 2019 but decreased to spine surgeons, largely due to decreasing payments from eight device manufacturers with the highest level of surgeon payments. A small subset of spine surgeons continues to receive increasing payments. The implications of decreasing investments in research by industry and of large payments made to a small group of spine surgeons bears cautious oversight, both for the future of the specialty and any impact on patient care outcomes.     

Conflict of interest disclosure in orthopaedic and general surgical trauma literature

SignificanceFinancial relationships between industry and physicians are a key aspect for the advancement of surgical practice and training, but these relationships also result in a conflict of interest with respect to research. Financial payments to physicians are public within the United States in the Open Payments Database, but the rate of accurate financial disclosure of payments has not previously been studied in trauma surgery publications.ObjectiveTo determine the rate of accurate financial disclosure in major surgical trauma journals compared with the Open Payments Database.Materials and MethodsThe names of all authors publishing in The Journal of Orthopaedic Trauma, Injury, and The Journal of Trauma and Acute Care Surgery between 2015 and 2018 were obtained from MEDLINE. Non-physicians, physicians outside of the United States, physicians without payments in the Open Payments Database, and physicians with payments types of only “Food and Drink” were excluded. Financial disclosure statements were obtained from the journal websites and manually compared against Open Payments Database entries the year prior to submission and during the year of submission up until 3 months prior to publication for each individual physician. Main outcomes were accuracy of disclosure published with each article, total amount of payments received (disclosure or undisclosed), surgical subspecialty of the reporting physician. Statistical comparisons were made using Chi-square testing with significance defined as p<0.05.ResultsBetween 2015 and 2018, 5070 articles were published involving 28,948 authors. 2945 authors met inclusion criteria. 490 authors accurately disclosed their financial relationships with industry (16.6%). The median value of undisclosed payments was $22,140 [IQR $6465, $77,221] which was significantly less than the medial value of disclosed payment of $66,433 [IQR $24,624, $161,886], p<0.001 Orthopaedic surgeons disclosed at a higher rate (26.3%, 479/1818) than general surgeons (4.8%, 47/971), p<0.001.ConclusionsPhysician-industry relationships are key for advancing surgical practice and providing training to physicians. These relationships are not inherently unethical, but there is consistently high inaccuracy of financial disclosure across multiple trauma surgery journals which may indicate the need for further education on financial disclosures during surgical training or active obtainment of publicly available financial disclosures by journals.     

Discrepancies in spine surgeon conflict of interest disclosures between a national meeting and physician payment listings on device manufacturer web sites

Background contextPrevious studies have identified inconsistencies in physician conflict-of-interest disclosures at academic meetings. The Physician Payment Sunshine Act (PPSA) will require industry to disclose anything of value given to physicians by 2014. In preparation, some spine device companies have begun reporting payments online.PurposeTo evaluate potential inconsistencies between physician disclosures and payments reported by industry before the PPSA implementation.Study designComparison of publically available disclosure/payment data.Patient samplePhysicians participating in the 2011 North American Spine Society (NASS) annual meeting and physicians listed on the 2010 physician payment web sites of Medtronic and Depuy Spine.MethodsDisclosures of participants at NASS were compared with the published Medtronic and Depuy Spine physician payments. The periods reflected by the disclosures compared should have coincided (except the Depuy site, which was only listed for one quarter of the NASS disclosure period). Discrepancies were noted whenever participant disclosures and company listings did not match as well as whenever payment ranges did not overlap. Fisher's exact test was used to compare disclosure discrepancy rates based on Medtronic payment size. No funding was received for this work. The authors report no conflicts of interest directly related to this study; however, one of the authors does do consulting unrelated to this study.ResultsMedtronic and Depuy Spine were disclosed by 12.1% and 8.75% of NASS participants, respectively. Based on NASS disclosures, 52.4% of NASS participants affiliated with Medtronic had their disclosures inaccurately reflected on the Medtronic web site. Based on Medtronic payment postings, 45.7% of NASS participants listed on Medtronic's webpage had discrepancies in their NASS disclosures. Those who received payments <$100,000 from Medtronic were more likely to have discrepancies in their disclosures than those who received payments >$100,000 (p=.009). Based on Depuy Spine payment postings, 30% of NASS participants listed on Depuy Spine's site had discrepancies in their NASS disclosures.ConclusionsDiscrepancy rates between what spine surgeons disclosed at NASS 2011 and what companies reported for their consultants were high. This is concerning given the passage of the PPSA as well as the increased public visibility of potential discrepancies. More uniform practices will certainly be necessary.     

Industry Payments and Their Association With Academic Influence in Total Joint Arthroplasty

BackgroundThe relationship between industry payments and academic influence, as measured by the Hirsch index (h-index) and number of publications, among adult reconstruction surgeons is not well characterized. The aims of the present study are to determine the relationship between an adult reconstruction surgeons’ academic influence and their relevant industry payments and National Institutes of Health (NIH) funding.MethodsAdult reconstruction surgeons were identified through the websites for the orthopedic surgery residency programs in the United States during the 2019-2020 academic year.Academic influence was approximated by each physician’s h-index and total number of publications. Industry payment data were obtained through the Open Payments Database, and NIH funding was determined through the NIH website. Mann-Whitney U testing and Spearman correlations were performed to examine relevant associations.ResultsSurgeons who received industry research payments had a higher mean h-index (16.1 vs 10.2, P < .001) and mean number of publications (79.1 vs 35.9, P < .001) than physicians who received no industry research payments. Surgeons receiving NIH funding had a higher mean h-index (48.1 vs 10.4, P < .001) and mean number of publications (294.5 vs 36.8, P < .001) than surgeons who did not receive NIH funding. There was no association between the average h-index (P = .668) and number of publications (P = .387) among adult reconstruction surgeons receiving industry nonresearch funding.Conclusionh-index and total publications do not seem to be associated with industry nonresearch payments in the field of total joint arthroplasty. Altogether, these data suggest that industry bias may not play a strong role in total joint arthroplasty.     

Risk Factors for Infection With Carbapenem‐Resistant Klebsiella pneumoniae After Liver Transplantation: The Importance of Pre‐ and Posttransplant Colonization

Improved understanding of risk factors associated with carbapenem‐resistant‐Klebsiella pneumoniae (CR‐KP) infection after liver transplantation (LT) can aid development of effective preventive strategies. We performed a prospective cohort study of all adult patients undergoing LT at our hospital during 30‐month period to define risk factors associated with CR‐KP infection. All patients were screened for CR‐KP carriage by rectal swabs before and after LT. No therapy was administered to decolonize or treat asymptomatic CR‐KP carriers. All patients were monitored up to 180 days after LT. Of 237 transplant patients screened, 41 were identified as CR‐KP carriers (11 at LT, 30 after LT), and 20 developed CR‐KP infection (18 bloodstream‐infection, 2 pneumonia) a median of 41.5 days after LT. CR‐KP infection rates among patients non‐colonized, colonized at LT, and colonized after LT were 2%, 18.2% and 46.7% (p < 0.001). Independent risk factors for CR‐KP infection identified by multivariate analysis, included: renal‐replacement‐therapy; mechanical ventilation > 48 h; HCV recurrence, and colonization at any time with CR‐KP. Based on these four variables, we developed a risk score that effectively discriminated patients at low versus higher risk for CR‐KP infection (AUC 0.93, 95% CI 0.86–1.00, p < 0.001). Our results may help to design preventive strategies for LT recipients in CR‐KP endemic areas.     

Industry Payments to Adult Reconstruction-Trained Orthopedic Surgeons: An Analysis of the Open Payments Database From 2014 to 2019

BackgroundIn recent time, there has been an increased push toward transparency in industry funding toward physicians. The Physician Payments Sunshine Act called for the creation of the Open Payments Database managed by the Centers for Medicare & Medicaid Services. To our knowledge, there have been no studies evaluating the trends in payments among adult reconstruction fellowship-trained orthopedic surgeons. The purpose of this study is to investigate trends in all payments to adult reconstruction-trained orthopedic surgeons from 2014 to 2019. Secondary outcomes included evaluating trends in yearly subpayment categories, regional variations, as well as characterizing the top 5 industry companies.MethodsA review of the Centers for Medicare & Medicaid Services Open Payments Database was performed to identify all payments to adult reconstruction-trained orthopedic surgeons. A total of 94,265 payments were made to 4911 surgeons accounting for a total of $258,865,231.20 during the study period. Our primary outcome was to assess the trend in median payment per year to individual surgeons. Secondary outcomes included evaluating payment trends with respect to subtype, location as defined by United States Census regions, as well as specifics concerning the top 5 companies.ResultsOver the study period, there was a nonsignificant increasing trend in median payment per surgeon (r = 0.49, P = .096). However, there was also a significantly increasing trend in the number of payments per year (r = 0.83, P = .014), as well as the number of surgeons receiving payments (r = 0.88, P = .019). With respect to subcategory payments, there were significantly increasing trends in the median payment per surgeon for education (1054%, r = 0.942, P < .001) and entertainment/food and beverage expenses (20.2%, r = 0.49, P = .020), as well as a significantly decreasing trend for median honoraria payments per surgeon (20.2%, r = −0.04, P = .005). No significant regional trends were identified. Of the top 5 companies, one demonstrated a significantly decreasing trend in median payment per surgeon (21.6%, r = −0.109, P < .001), whereas the others remained unchanged.ConclusionIn this study, we found a nonsignificant increasing trend in payments to adult reconstruction-trained surgeons as well as an increasing number of surgeons receiving payments. There were increasing trends in median payment per surgeon for education and entertainment expenses, but a decreasing trend for honoraria payments. No significant regional trends were identified. The majority of the top 5 companies had nonsignificant trends in their payments. Further studies are needed to characterize the disclosure of payments and the impact of industry payments on clinical outcomes.Level of EvidenceIV.     

Variation in Biliary Complication Rates Following Liver Transplantation: Implications for Cost and Outcome

Although biliary complications (BCs) have a significant impact on the outcome of liver transplantation (LT), variation in BC rates among transplant centers has not been previously analyzed. BC rate, LT outcome and spending were assessed using linked Scientific Registry of Transplant Recipients and Medicare claims (n = 16 286 LTs). Transplant centers were assigned to BC quartiles based upon risk‐adjusted observed to expected (O:E) ratio of BC separately for donation after brain death (DBD) and donation after cardiac death (DCD) donors. The median incidence of BC was 300% greater in the highest versus lowest DBD quartiles (19.0% vs. 5.9%) and varied 250% between DCD quartiles (20.3%–8.4%). Donor and recipient characteristics suggest that high BC centers actually used lower donor risk index organs, fewer split livers and fewer imports (p < 0.001 for all). Transplant at a center in the highest O:E quartile was associated with increased posttransplant mortality (adjusted hazard ratio [aHR] 2.53, p = 0.007) in DCD transplant and increased graft loss (aHR 1.21, p = 0.02) in DBD transplant. Medicare spending was $22 895 (p < 0.0001) higher at centers in highest versus lowest BC quartile. In summary, BC rates vary widely among transplant centers and higher rates are a marker for an increased risk of death, graft failure and health‐care spending.     

Economic Impacts of ABO‐Incompatible Live Donor Kidney Transplantation: A National Study of Medicare‐Insured Recipients

The infrequent use of ABO‐incompatible (ABOi) kidney transplantation in the United States may reflect concern about the costs of necessary preconditioning and posttransplant care. Medicare data for 26 500 live donor kidney transplant recipients (2000 to March 2011), including 271 ABOi and 62 A2‐incompatible (A2i) recipients, were analyzed to assess the impact of pretransplant, transplant episode and 3‐year posttransplant costs. The marginal costs of ABOi and A2i versus ABO‐compatible (ABOc) transplants were quantified by multivariate linear regression including adjustment for recipient, donor and transplant factors. Compared with ABOc transplantation, patient survival (93.2% vs. 88.15%, p = 0.0009) and death‐censored graft survival (85.4% vs. 76.1%, p < 0.05) at 3 years were lower after ABOi transplant. The average overall cost of the transplant episode was significantly higher for ABOi ($65 080) compared with A2i ($36 752) and ABOc ($32 039) transplantation (p < 0.001), excluding organ acquisition. ABOi transplant was associated with high adjusted posttransplant spending (marginal costs compared to ABOc ‐ year 1: $25 044; year 2: $10 496; year 3: $7307; p < 0.01). ABOi transplantation provides a clinically effective method to expand access to transplantation. Although more expensive, the modest increases in total spending are easily justified by avoiding long‐term dialysis and its associated morbidity and cost.     

Increased Patient-Level Payment After Removal of Total Knee Arthroplasty From the Inpatient-Only List

BackgroundIn January 2018, the Centers for Medicare and Medicaid Services removed total knee arthroplasty (TKA) from the Inpatient Only (IPO) list. This study aimed to compare patient-level payments in TKA cases with a length of stay (LOS) <2 midnights before and after removal of TKA from IPO list.MethodsIn this retrospective cohort study, all Medicare patients who received a primary elective TKA from 2016-2019 with a LOS <2 midnights at an academic tertiary center were identified. Total and itemized charges and patient-level payments were compared between eligible TKA cases performed in 2016-2017 and those in 2018-2019. There were 351 eligible TKA cases identified: 151 in 2016-2017 and 200 in 2018-2019.ResultsThe percentage of patients making any out-of-pocket payment increased in 2018-2019 from 2016-2017 (51.0% versus 10.6%), as did median patient-level payment ($7.30 [range, $0.00-$3,389] versus $0.00 [range, $0.00-$1,248], P < .001 for both). A greater proportion of patients in 2018-2019 paid $1-$50 than in 2016-2017 (37.5% versus 1.3%, P < .001) with no change in the proportion of patients who made payments >$50. Total charges were less in 2018-2019 than in 2016-2017 (P = .001). Charges for drugs, laboratory tests, admissions/floor, and therapies decreased in 2018-2019, whereas charges for the operating room and radiology increased (P < .001 for all).ConclusionPatients receiving outpatient TKA in 2018-2019 were more likely to have out-of-pocket payments than patients with comparable hospital stay who were designated as inpatients, although most of these payments were less than $50.     

Donation after Cardiac Death Liver Transplantation: Predictors of Outcome

We aimed to identify recipient, donor and transplant risk factors associated with graft failure and patient mortality following donation after cardiac death (DCD) liver transplantation. These estimates were derived from Scientific Registry of Transplant Recipients data from all US liver‐only DCD recipients between September 1, 2001 and April 30, 2009 (n = 1567) and Cox regression techniques. Three years post‐DCD liver transplant, 64.9% of recipients were alive with functioning grafts, 13.6% required retransplant and 21.6% died. Significant recipient factors predictive of graft failure included: age ≥ 55 years, male sex, African–American race, HCV positivity, metabolic liver disorder, transplant MELD ≥ 35, hospitalization at transplant and the need for life support at transplant (all, p ≤ 0.05). Donor characteristics included age ≥ 50 years and weight >100 kg (all, p ≤ 0.005). Each hour increase in cold ischemia time (CIT) was associated with 6% higher graft failure rate (HR 1.06, p < 0.001). Donor warm ischemia time ≥ 35 min significantly increased graft failure rates (HR 1.84, p = 0.002). Recipient predictors of mortality were age ≥ 55 years, hospitalization at transplant and retransplantation (all, p ≤ 0.006). Donor weight >100 kg and CIT also increased patient mortality (all, p ≤ 0.035). These findings are useful for transplant surgeons creating DCD liver acceptance protocols.     

Survival Advantage of Pediatric Recipients of a First Kidney Transplant Among Children Awaiting Kidney Transplantation

The mortality rate in children with ESRD is substantially lower than the rate experienced by adults. However, the risk of death while awaiting kidney transplantation and the impact of transplantation on long‐term survival has not been well characterized in the pediatric population. We performed a longitudinal study of 5961 patients under age 19 who were placed on the kidney transplant waiting list in the United States. Of these, 5270 received their first kidney transplant between 1990 and 2003. Survival was assessed via a time‐varying nonproportional hazards model adjusted for potential confounders. Transplanted children had a lower mortality rate (13.1 deaths/1000 patient‐years) compared to patients on the waiting list (17.6 deaths/1000 patient‐years). Within the first 6 months of transplant, there was no significant excess in mortality compared to patients remaining on the waiting list (adjusted Relative Risk (aRR) = 1.01; p = 0.93). After 6 months, the risk of death was significantly lower: at 6–12 months (aRR = 0.37; p < 0.001) and at 30 months (aRR 0.26; p < 0.001). Compared to children who remain on the kidney transplant waiting list, those who receive a transplant have a long‐term survival advantage. With the potential for unmeasured bias in this observational data, the results of the analysis should be interpreted conservatively.     

The clinical significance of intrapulmonary vascular dilations in liver transplant candidates

Intrapulmonary vascular dilations (IPVD) are common in patients with cirrhosis, but the majority do not have hepatopulmonary syndrome (HPS). The clinical significance of IPVD is unknown. Our aim was to determine the clinical impact due to the entire spectrum of IPVD in liver transplant (LT) candidates. A total of 122 evaluees for LT underwent contrast transthoracic echocardiography (cTTE). The degree of shunting was graded 1–3 (severe). HPS was defined as PaO₂ < 70 mmHg in the presence of IPVD and exclusion of other causes of hypoxemia. IPVD were detected in 57/122 (47%), and of these HPS was found in 5. IPVD were associated with higher Alveolar‐arterial (A‐a) gradients, with the highest occurring in patients with HPS (IPVD vs. no IPVD: p = 0.003; HPS vs. no IPVD: p = 0.004). All patients with HPS had grade 3 shunting, and had significantly widened A‐a gradient and lower PaO₂ compared with grade 1 or 2 IPVDs. Presence of IPVD did not affect survival measured from evaluation or after LT. Other clinical outcomes were also similar among patients with and without IPVD. IPVD are common among LT candidates. HPS is unlikely in presence of only mild to moderate shunting. Clinical outcomes are similar among patients with and without IPVD.     

Transplant physician and surgeon compensation: A sample framework accounting for nonbillable and value‐based work

Work relative value unit (wRVU)–based fee schedules are predominantly used by both the Centers for Medicare & Medicaid Services (CMS) and private payers to determine the payments for physicians' clinical productivity. However, under the Affordable Care Act, CMS is transitioning into a value‐based payment structure that rewards patient‐oriented outcomes and cost savings. Moreover, in the context of solid organ transplantation, physicians and surgeons conduct many activities that are neither billable nor accounted for in the wRVU models. New compensation models for transplant professionals must (1) justify payments for nonbillable work related to transplant activity/procedures; (2) capture the entire academic, clinical, and relationship‐building work effort as part of RVU determination; and (3) move toward a value‐based compensation scheme that aligns the incentives for physicians, surgeons, transplant center, payers, and patients. In this review, we provide an example of redesigning RVUs to address these challenges in compensating transplant physicians and surgeons. We define a customized RVU (cRVU) for activities that typically do not generate wRVUs and create an outcome value unit (OVU) measure that incorporates outcomes and cost savings into RVUs to include value‐based compensation.     

The Long‐Term Benefit of Liver Transplantation for Hepatic Metastases From Neuroendocrine Tumors

Selection criteria and benefit of liver transplantation for hepatic metastases from neuroendocrine tumors (NETs) remain uncertain. Eighty‐eight consecutive patients with metastatic NETs eligible for liver transplantation according to Milan‐NET criteria were offered transplant (n = 42) versus nontransplant options (n = 46) depending on list dynamics, patient disposition, and age. Tumor burden between groups did not differ. Transplant patients were younger (40.5 vs. 55.5 years; p < 0.001). Long‐term outcomes were compared after matching between groups made on multiple Cox models adjusted for propensity score built on logistic models. Survival benefit was the difference in mean survival between transplant versus nontransplant options. No patients were lost or died without recurrence. Median follow‐up was 122 months. The transplant group showed a significant advantage over nontransplant strategies at 5 and 10 years in survival (97.2% and 88.8% vs. 50.9% and 22.4%, respectively; p < 0.001) and time‐to‐progression (13.1% and 13.1% vs. 83.5% and 89%; p < 0.001). After adjustment for propensity score, survival advantage of the transplant group was significant (hazard ratio = 7.4; 95% confidence interval (CI): 2.4–23.0; p = 0.001). Adjusted transplant‐related survival benefit was 6.82 months (95% CI: 1.10–12.54; p = 0.019) and 38.43 months (95% CI: 21.41–55.45; p < 0.001) at 5 and 10 years, respectively. Liver transplantation for metastatic NETs under restrictive criteria provides excellent long‐term outcome. Transplant‐related survival benefit increases over time and maximizes after 10 years.     

Improved Survival After Liver Transplantation in Patients with Hepatopulmonary Syndrome

Hepatopulmonary syndrome (HPS) is present in 10–32% of chronic liver disease patients, carries a poor prognosis and is treatable by liver transplantation (LT). Previous reports have shown high LT mortality in HPS and severe HPS (arterial oxygen (PaO₂) ≤50 mmHg). We reviewed outcomes in HPS patients who received LT between 2002 and 2008 at two transplant centers supported by a dedicated HPS clinic. We assessed mortality, complications and gas exchange in 21 HPS patients (mean age 51 years, MELD score 14), including 11/21 (52%) with severe HPS and 5/21 (24%) with living donor LT (median follow‐up 20.2 months after LT). Overall mortality was 1/21 (5%); mortality in severe HPS was 1/11 (9%). Peritransplant hypoxemic respiratory failure occurred in 5/21 (24%), biliary complications in 8/21 (38%) and bleeding or vascular complications in 6/21 (29%). Oxygenation improved in all 19 patients in whom PaO₂ or SaO₂ were recorded. PaO₂ increased from 52.2 ± 13.2 to 90.3 ± 11.5 mmHg (room air) (p < 0.0001) (12 patients); a higher baseline macroaggregated albumin shunt fraction predicted a lower rate of postoperative improvement (p = 0.045) (7 patients). Liver transplant survival in HPS and severe HPS was higher than previously demonstrated. Severity of HPS should not be the basis for transplant refusal.     

Donor and Recipient IL28B Polymorphisms in HCV‐Infected Patients Undergoing Antiviral Therapy before and after Liver Transplantation

IL28B gene polymorphisms are associated with the response to antiviral therapy in hepatitis C patients. We investigated the influence of IL28B polymorphisms on the response to therapy before and after liver transplantation (LT). Genotyping of SNPs rs8099917 and rs12979860 was performed in 128 HCV‐infected liver transplant recipients and in their donors; all patients underwent antiviral treatment after LT. The prevalence of genotypes rs12979860CC and rs8099917TT was higher in donors than in recipients (50% vs.19%, p < 0.001 and 67% vs. 38%, p < 0.001, respectively). Response to antiviral therapy was significantly higher for recipient genotype rs12979860CC as compared to rs12979860CT/TT both before (100% vs. 48% p = 0.013) and after LT (59% vs. 25% p = 0.002). The figures were almost identical for SNP rs8099917. Sustained virological response after LT was particularly high in patients with favorable recipient and donor genotypes (p < 0.01 for both SNPs). In a subgroup of 34 patients treated while awaiting LT, a favorable donor IL28B genotype was associated with an improved virological response after LT. Our results support a major role of recipient IL28B genotype in the response to antiviral treatment for hepatitis C recurrence. Interestingly, donor genotype also seems to influence the response pattern, especially in recipients who have a favorable IL28B genotype.     

Decreasing plasma soluble IL‐1 receptor antagonist and increasing monocyte activation early post‐transplant may be involved in pathogenesis of delayed graft function in renal transplant recipients

Sadeghi M, Daniel V, Naujokat C, Schmidt J, Mehrabi A, Zeier M, Opelz G. Decreasing plasma soluble IL‐1 receptor antagonist and increasing monocyte activation early post‐transplant may be involved in pathogenesis of delayed graft function in renal transplant recipients
Clin Transplant 2010: 24: 415–423. © 2009 John Wiley & Sons A/S. Abstract: Delayed graft function (DGF) increases the risk of acute allograft rejection and may affect long‐term graft survival. We compared pre‐transplant, early post‐transplant, and late post‐transplant serum creatinine (Cr) and plasma levels of neopterin, cytokines, and cytokine receptors/antagonists in patients with DGF (n = 39), slow graft function (SGF) (n = 43), or immediate graft function (IGF) (n = 30). Three and eight days post‐transplant, plasma neopterin (p < 0.001; p < 0.001), Soluble Interleukin‐6 (IL‐6) receptor (R) (p = 0.002; p = 0.001), and IL‐10 (p = 0.003; p = 0.001) were higher in DGF than IGF patients. One month post‐transplant, plasma neopterin (p < 0.001) and IL‐10 (p < 0.001) were higher in DGF than IGF patients. Three days post‐transplant, the results indicated reduced sIL‐1 receptor antognist (RA) production in DGF patients (p = 0.001). Simultaneously, plasma sIL‐6R and IL‐10 increased in DGF (p < 0.001; p = 0.003) and SGF (p = 0.007; p = 0.030) patients, indicating increased production of sIL‐6R and IL‐10. Lower sIL‐1 production in DGF than IGF patients early post‐transplant might promote the increased production of monocyte‐derived neopterin, sIL‐6R, and IL‐10. This monocyte/macrophage activation might induce inflammation in the graft and subsequently cause an impairment of graft function. Blocking of monocyte activity after renal transplantation may be considered a potential approach for improving graft outcome.