Characterizing the risk of human leukocyte antigen-incompatible living donor kidney transplantation in older recipients.

Older compatible living donor kidney transplant (CLDKT) recipients have higher mortality and death-censored graft failure (DCGF) compared to younger recipients. These risks may be amplified in older incompatible living donor kidney transplant (ILDKT) recipients who undergo desensitization and intense immunosuppression. In a 25-center cohort of ILDKT recipients transplanted between September 24, 1997, and December 15, 2016, we compared mortality, DCGF, delayed graft function (DGF), acute rejection (AR), and length of stay (LOS) between 234 older (age ≥60 years) and 1172 younger (age 18-59 years) recipients. To investigate whether the impact of age was different for ILDKT recipients compared to 17 542 CLDKT recipients, we used an interaction term to determine whether the relationship between posttransplant outcomes and transplant type (ILDKT vs CLDKT) was modified by age. Overall, older recipients had higher mortality (hazard ratio: 1.632.072.65, P < .001), lower DCGF (hazard ratio: 0.360.530.77, P = .001), and AR (odds ratio: 0.390.540.74, P < .001), and similar DGF (odds ratio: 0.461.032.33, P = .9) and LOS (incidence rate ratio: 0.880.981.10, P = 0.8) compared to younger recipients. The impact of age on mortality (interaction P = .052), DCGF (interaction P = .7), AR interaction P = .2), DGF (interaction P = .9), and LOS (interaction P = .5) were similar in ILDKT and CLDKT recipients. Age alone should not preclude eligibility for ILDKT.

The demise of islet allotransplantation in the United States: A call for an urgent regulatory update.

Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state-of-the-art in clinical or technical practices. In the US, islets are considered biologic drugs and "more than minimally manipulated" human cell and tissue products (HCT/Ps). In contrast, across the world, human islets are appropriately defined as "minimally manipulated tissue" and not regulated as a drug, which has led to islet allotransplantation (allo-ITx) becoming a standard-of-care procedure for selected patients with type 1 diabetes mellitus. This regulatory distinction impedes patient access to islets for transplantation in the US. As a result only 11 patients underwent allo-ITx in the US between 2016 and 2019, and all as investigational procedures in the settings of a clinical trials. Herein, we describe the current regulations pertaining to islet transplantation in the United States. We explore the progress which has been made in the field and demonstrate why the regulatory framework must be updated to both better reflect our current clinical practice and to deal with upcoming challenges. We propose specific updates to current regulations which are required for the renaissance of ethical, safe, effective, and affordable allo-ITx in the United States.

Delayed graft function and acute rejection following HLA-incompatible living donor kidney transplantation.

Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR = 1.03 1.682.72 ). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction > .1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF = 1.45 2.093.02 ; PFNC = 1.67 2.403.46 ; PCC = 1.48 2.243.37 ). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction = .1), its impact on DCGF risk was less consequential for ILDKT (aHR = 1.34 1.621.95 ) than CLDKT (aHR = 1.96 2.292.67 ) (p interaction = .004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.

Visualization of adult fish lens fiber cells.

The crystalline lens of a vertebrate eye is a gradient-index lens and grows throughout life by addition of new lens fiber cells in the periphery. In fish, the growing ball-shaped lens maintains sophisticated optical properties throughout life by maintaining the distribution of refractive index relative to the increasing radius of the lens. During this process, the central fibers must increase refractive index by increasing the cytosolic concentration of crystallin proteins. However, only the youngest, most peripheral lens fiber cells have the ability to synthesize proteins. Unfortunately, the hardness of fish lenses makes investigation of the cellular anatomy impossible with traditional histological methods. We have developed a method for visualizing lens fiber cells across the diameter of the lens in adult fish. The method relies on sectioning embedded lenses with a high-speed power saw and observing the cut surface with a scanning electron microscope (SEM). The combination of SEM and image analysis allowed for precise tracking of the positions of individual cell fiber cells. As an application of the method, we present a cell thickness profile, i.e. the distribution of cells thicknesses and their relative positions along the lens's radius. Combined with detailed optical studies, which by mathematical reasons only are possible on ball-shaped lenses, our method can lead to new insights into the mechanism governing the functional and cellular development of vertebrate lenses.

Activation of CB1 receptors by 2-arachidonoylglycerol attenuates vasoconstriction induced by U46619 and angiotensin II in human and rat pulmonary arteries.

Recent evidence suggests that endocannabinoids acting via cannabinoid CB1 receptors may modulate vascular responses of various vasoconstrictors in the rodent systemic vasculature. The aim of the study was to investigate whether endocannabinoids modulate the contractile responses evoked by a thromboxane A2 analog (U46619), angiotensin II (ANG II), serotonin (5-HT), and phenylephrine, which stimulate distinct Gq/11 protein-coupled receptors (thromboxane, ANG II type 1, 5-HT2, and α1-adrenergic receptors) in isolated endothelium-intact human and rat pulmonary arteries (hPAs and rPAs, respectively). The CB1 receptor antagonist AM251 (1 µM) and diacylglycerol lipase (2-arachidonoylglycerol synthesis enzyme) inhibitor RHC80267 (40 µM) enhanced contractions induced by U46619 in hPAs and rPAs and by ANG II in rPAs in an endothelium-dependent manner. AM251 did not influence vasoconstrictions induced by 5-HT or phenylephrine in rPAs. The monoacylglycerol lipase (2-arachidonoylglycerol degradation enzyme) inhibitor JZL184 (1 µM), but not the fatty acid amide hydrolase (anandamide degradation enzyme) inhibitor URB597 (1 µM), attenuated contractions evoked by U46619 in hPAs and rPAs and ANG II in rPAs. 2-Arachidonoylglycerol concentration-dependently induced relaxation of hPAs, which was inhibited by endothelium denudation or AM251 and enhanced by JZL184. Expression of CB1 receptors was confirmed in hPAs and rPAs using Western blotting and immunohistochemistry. The present study shows the protective interaction between the endocannabinoid system and vasoconstriction in response to U46619 and ANG II in the human and rat pulmonary circulation. U46619 and ANG II may stimulate rapid endothelial release of endocannabinoids (mainly 2-arachidonoylglycerol), leading to CB1 receptor-dependent and/or CB1 receptor-independent vasorelaxation, which in the negative feedback mechanism reduces later agonist-induced vasoconstriction.

C4d-expressing glomerulopathy and proteinuria post transplantation of a too-big-for-size mismatched kidney allograft: An unusual case with good outcome
.

A 5-year-old severely growth-retarded child with tubulointerstitial, oliguric end-stage renal disease received an adult-size kidney transplant. Three years post grafting under standard triple immunosuppression (mycophenolate mofetil, tacrolimus, and prednisone) de novo nephrotic range proteinuria without the nephrotic syndrome developed. Graft function was normal (serum creatinine: 0.2 - 0.3 mg/dL), there were no donor-specific HLA antibodies (DSA), and the urine sediment was inactive. Two biopsies collected 3 and 4 years post-transplantation showed severe glomerular capillary wall remodeling and associated pseudolinear C4d staining as morphologic correlates for the proteinuria. Changes resembled those seen in so-called "size-mismatch transplant glomerulopathies". There was no evidence of a glomerulonephritis, acute or chronic rejection including transplant glomerulopathy, interstitial fibrosis, peritubular capillary C4d deposits, or multilamination of peritubular capillary basement membranes. The glomerular changes were not detected in the implantation zero-hour biopsy or the recipient's native renal biopsy. At the end of follow-up 64 months post transplantation, proteinuria persisted at subnephrotic levels in the setting of stable graft function and undetectable DSAs. This unique case adds to the list of causes of nonrejection-associated post-transplant proteinuria. It demonstrates for the first time that a too-large-for-body-size mismatched graft is associated with a presumably sheer stress-induced C4d expressing glomerulopathy, severe proteinuria, and favorable outcome.
.

Analysis of medieval mtDNA from Napole cemetery provides new insights into the early history of Polish state.

Contemporary historical anthropology and classical archaeology are concerned not only with such fundamental issues as the origins of ancient human populations and migration routes, but also with the formation and development of inter-population relations and the mixing of gene pools as a result of inter-breeding between individuals representing different cultural units. The contribution of immigrants to the analysed autochthonous population and their effect on the gene pool of that population has proven difficult to evaluate with classical morphological methods. The burial of one individual in the studied Napole cemetery located in central Poland had the form of a chamber grave, which is typical of Scandinavian culture from that period. However, this fact cannot be interpreted as absolute proof that the individual (in the biological sense) was allochtonous. This gives rise to the question as to who was actually buried in that cemetery. The ancient DNA results indicate that one of the individuals had an mtDNA haplotype typical of Iron Age northern Europe, which suggests that he could have arrived from that area at a later period. This seems to indirectly confirm the claims of many anthropologists that the development of the early medieval Polish state was significantly and directly influenced by the Scandinavians.

Differences in lens optical plasticity in two gadoid fishes meeting in the Arctic.

Arctic and boreal/temperate species are likely to be evolutionary adapted to different light regimes. Currently, the boreal/temperate Atlantic cod (Gadus morhua) is coexisting with the native polar cod (Boreogadus saida) in the Arctic waters around Svalbard, Norway. Here, we studied light/dark adaptative optical plasticity of their eye lenses by exposing fish to bright light during the polar night. Schlieren photography, high-definition laser scanning and ray tracing were used to determine the optical properties of excised crystalline lenses. Both species have multifocal lenses, an optical adaptation for improved color vision. In polar cod, the optical properties of the lens were independent of light exposure. In the more southern Atlantic cod, the optical properties of the lens changed within hours upon exposure to light, even after months of darkness. Such fast optical adjustment has previously only been shown in a tropical cichlid. During the polar night the Atlantic cod lens seems to be unregulated and dysfunctional since it had an unsuitable focal length and severe spherical aberration. We present a system, to our knowledge unique, for studying visual plasticity on different timescales in relation to evolutionary history and present the first study on the polar cod visual system.

Using expert-reviewed CSAM to train CNNs and its anthropological analysis.

Machine learning methods for the identification of child sexual abuse materials (CSAM) have been previously studied, however, they have serious limitations. Firstly, the training sets used to train the appropriate machine learning algorithms were not previously annotated by a forensic expert in anthropology. Secondly, previously presented solutions have rarely used models trained using real pornographic content involving children. Thirdly, previous studies have not presented a detailed justification for the classification decisions made, which is important due to the recent guidelines of the European Commission (Artificial Intelligence Act). The aim of the study was to train convolution neural networks (CNNs) using expert-labelled CSAM images and thereby identify the elements of the body and/or the environment that are critical for classifications by the neural network. To train and evaluate machine learning models, we used 60,000 images equally divided into four classes (CSAM images, images displaying sexual activity involving adults, images of people without sexual activity, and images not containing people). We used four neural network architectures: MobileNet, ResNet152, xResNet152 and its modification ResNet-s, designed for the purpose of research. The trained models provided high accuracy of classifying CSAM images: xResNet152 (F1 = 0.93, 92,8%), xResNet-s (F1 = 0.93, 93,1%), ResNet152 (F1 = 0.90, 91,39%), MobileNet (F1 ranged from 0.85 to 0.87, accuracy ranged from 86% to 87%). The results of the conducted research suggest that using expert knowledge (in sexology and anthropology) significantly improved the accuracy of the models. In regard to further anthropological analysis, the results indicate that the breasts, face and torso are crucial areas for the classification of pornographic content with children's participation. Results suggests that the ResNet-s neural network may be a reliable tool for clinical work and to support the work of experts witnesses in the field of anthropology. The study design received a positive opinion of the Ethics Committee of the Faculty of Mathematics, Informatics and Mechanics of the University of Warsaw. The clinical material was used for research purposes with the consent of the relevant prosecutor's offices. Authors provided free version of Windows application to classify CSAM for forensic experts, policemen and prosecutors at the OSF repository (DOI: 10.17605/OSF.IO/RU7JX).

Mobility of Zn and Cu in Bentonites: Implications for Environmental Remediation.

The aim of this study was to evaluate the mobility of copper (Cu) and zinc (Zn) and their impact on the properties of bentonites and unfrozen water content. Limited research in this area necessitates further analysis to prevent the negative effects of metal interactions on bentonite effectiveness. Tests involved American (SWy-3, Stx-1b) and Slovak (BSvk) bentonite samples with Zn or Cu ion exchange. Sequential extraction was performed using the Community Bureau of Reference (BCR) method. Elemental content was analyzed via inductively coupled plasma optical emission spectrometry (ICP-OES). Unfrozen water content was measured using nuclear magnetic resonance (1H-NMR) and differential scanning calorimetry (DSC). Results showed a significant influence of the main cation (Zn or Cu) on ion mobility, with toxic metal concentrations increasing mobility and decreasing residual fractions. Mobile Zn fractions increased with larger particle diameters, lower clay content, and shorter interplanar spacing, while the opposite was observed for Cu. Zn likely accumulated in larger clay pores, while Cu was immobilized in the bentonite complex. The stability of Zn or Cu ions increased with higher clay content or specific surface area. Residual Zn or Cu fractions were highest in uncontaminated bentonites with higher unfrozen water content, suggesting the potential formation of concentrated solutions in sub-zero temperatures, posing a threat to the clay-water environment, especially in cold regions.

Peripheral Brain-Derived Neurotrophic Factor (BDNF) and Its Regulatory miRNAs as Biological Correlates of Impulsivity in Young Adults.

Background: Impulsivity assessment may serve as a valuable clinical tool in the stratification of suicide risk. Acting without forethought is a crucial feature in the psychopathology of many psychiatric disturbances and corresponds with suicidal ideations, behaviors, and attempts. Methods: We present data on biological and psychological correlates of impulsivity among young adults (n = 47). Psychological analysis included both the self-description questionnaire-Barratt Impulsiveness Scale (BIS-11)-and neuropsychological behavioral tests, including the Iowa Gambling Task (IGT), the Simple Response Time task (SRT), and the Continuous Performance Test (CPT). mRNA and micro-RNA were isolated from peripheral blood mononuclear cells (PBMC). Expression levels of Brain-Derived Neurotrophic Factor (BDNF) mRNA and its regulatory micro RNAs, mir-1-3p, mir-15a-5p, mir-26a-5p, mir-26b-5p, and mir-195-5p, were analyzed using the quantitative reverse transcription polymerase chain reaction (RT-qPCR) method. proBDNF and BDNF plasma protein levels were quantified using enzyme-linked immunosorbent assay (ELISA). Results: Significant correlations between BDNF mRNA and mir-15a-5p as well as proBDNF levels and mir-1-3p were detected. proBDNF protein levels correlated with motor and perseverance, while mir-26b correlated with cognitive complexity subdimensions of the BIS-11 scale. Correlations between BDNF, miRNAs, and the results of neuropsychological tests were also detected. Conclusions: The BDNF pathway shows a clinical potential in searching for biomarkers of impulse-control impairment. BDNF-regulatory micro-RNAs are detectable and related to clinical parameters in the studied population, which needs further research.

The Potential Environmental and Social Influence of the Inorganic Salt Hydrates Used as a Phase Change Material for Thermal Energy Storage in Solar Installations.

The aim of this article is to assess the potential impact of inorganic salt hydrates used as PCM material in solar installations on the environment and human health and to assess the society's approach to this technology. The properties of salt are discussed in two ways: first, by analyzing the environmental and health problems caused by chemical hazards on the basis of the available material safety data sheets. Secondly, by analyzing the potential disadvantages of salt hydrates in terms of environmental hazards based on the results of experimental studies available in the literature. Then, using questionnaires, the public approach to solar installations with a built-in converter containing salt hydrates is assessed. Disodium hydrogen phosphate dodecahydrate turned out to be the most prospective salt in terms of environmental, thermophysical, and economic properties for use in solar installations. Understanding the attitudes of the local community toward technologies using inorganic salt hydrates will enable appropriate action to be taken in the future to promote their development. Surveys have shown great public concern about their impact on the environment and human health. In this regard, it is necessary to implement information and promotion activities.

Peripheral S100B Protein Levels in Five Major Psychiatric Disorders: A Systematic Review.

Five major psychiatric disorders: schizophrenia, major depressive disorder, bipolar disorder, autistic spectrum disorder, and attention-deficit/hyperactivity disorder, show a shared genetic background and probably share common pathobiological mechanisms. S100B is a calcium-binding protein widely studied in psychiatric disorders as a potential biomarker. Our systematic review aimed to compare studies on peripheral S100B levels in five major psychiatric disorders with shared genetic backgrounds to reveal whether S100B alterations are disease-specific. EMBASE, Web of Science, and PubMed databases were searched for relevant studies published until the end of July 2023. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA) guidelines. Overall, 1215 publications were identified, of which 111 full-text articles were included in the systematic review. Study designs are very heterogeneous, performed mostly on small groups of participants at different stages of the disease (first-episode or chronic, drug-free or medicated, in the exacerbation of symptoms or in remission), and various clinical variables are analyzed. Published results are inconsistent; most reported elevated S100B levels across disorders included in the review. Alterations in S100B peripheral levels do not seem to be disease-specific.

Sinusoidal C4d deposits in liver allografts indicate an antibody-mediated response: diagnostic considerations in the evaluation of liver allografts.

There is a paucity of data concerning the correlation of complement component 4d (C4d) staining in liver allografts and antibody-mediated rejection. Data about the location and character of C4d deposits in native and allograft liver tissues are inconsistent. We performed C4d immunofluorescence (IF) on 141 fresh-frozen liver allograft biopsy samples and native livers, documented the pattern of C4d IF staining, and correlated the findings with the presence of donor-specific alloantibodies (DSAs). A linear/granular sinusoidal pattern of C4d IF was noted in 18 of 28 biopsy samples obtained after transplantation from patients with positive crossmatch and detectable donor-specific alloantibody (pos-XM/DSA) findings. None of the 59 tested biopsy samples from patients with negative crossmatch and detectable donor-specific alloantibody (neg-XM/DSA) findings were C4d-positive (P < 0.001). No significant association was found between pos-XM/DSA and C4d IF staining in other nonsinusoidal liver compartments. To compare the results of sinusoidal C4d staining with IF and 2 immunohistochemistry (IHC) techniques, C4d IHC was performed on 19 liver allograft biopsy samples in which a sinusoidal pattern of C4d IF had been noted. Sinusoidal C4d IHC findings were negative for 17 of the 19 biopsy samples; 2 showed weak and focal staining, and both patients had pos-XM/DSA findings. Portal vein endothelium staining was present in only 1 IF-stained biopsy sample (pos-XM/DSA) but in 11 IHC-stained biopsy samples (2 of the 11 samples had neg-XM/DSA findings). We conclude that sinusoidal C4d deposits detected by IF in frozen tissue samples from liver allograft recipients correlate with the presence of DSAs and an antibody-mediated alloresponse. These observations are similar to findings reported for other solid organ transplants and can provide relevant information for patient management. Further validation of IHC techniques for C4d detection in liver allograft tissue is required.

Innovative diagnostic device for thickness measurement of conveyor belts in horizontal transport.

Diagnostics of conveyor belts used in horizontal transport without the need to take the belt off the conveyor and test it in laboratory conditions is an important aspect in mining plants (Jurdziak et al., Adv Intell Syst Comput, 835:645-654, 2019). Current testing, and thus obtaining knowledge about the current thickness of the conveyor belt covers, allows for control accelerated changes. It also avoids emergency stoppages in the operation of the conveyor and enables economically justified planning of a break in its operation. The article presents the concept of the first in Poland mobile device for measuring the thickness of conveyor belts in motion, implemented as part of the NCBR project (No. 0227 / L-10/2018 [LIDER program, Transport Przemyslowy i Maszyny Robocze, 1(47)/2020, pp. 60-61]), and also presents the measurement results obtained thanks to the laboratory version of the device.

Antioxidant and antiradical activities depend on adrenal tumor type.

The aim of the study was to assess the total antioxidant/oxidant status in the plasma and urine of patients with adrenal tumors. The study group consisted of 60 patients (31 women and 29 men) with adrenal masses, classified into three subgroups: non-functional incidentaloma, pheochromocytoma and Cushing's/Conn's adenoma. The number of patients was set a priori based on our previous experiment (α = 0.05, test power = 0.9). Antioxidant activity (Total Antioxidant Capacity (TAC), Total Oxidant Status (TOS), Oxidative Stress Index (OSI)) and antiradical activity (Radical-Scavenging Activity Assay (DPPH), Ferric-Reducing Antioxidant Power (FRAP)) were measured using colorimetric methods. FRAP level was decreased in plasma and urine incidentaloma (p<0.0001), pheochromocytoma (p<0.0001) and Cushing's/Conn's adenoma (p<0.0001), while DPPH antiradical activity only in plasma of patients with adrenal masses (p<0.0001). Plasma TAC was increased in incidentaloma patients (p=0.0192), whereas in pheochromocytoma group (p=0.0343) was decreased. Plasma and urine TOS (p<0.0001) and OSI (p<0.01) were significantly higher in patients with adrenal tumors. In pheochromocytoma patients, plasma and urine TAC (p=0.001; p=0.002), as well as plasma plasma DPPH (p=0.007) and urine FRAP (p=0.017) correlated positively with normethanephrine. We are the first who showed reduced radical scavenging capacity in the plasma/urine of patients with adrenal masses. Nevertheless, plasma TAC was significantly higher in the incidentaloma group compared to controls. Therefore, plasma and urinary antioxidant and antiradical activities depend on the presence of the tumor. Lower levels of TAC, DPPH and FRAP clearly indicate a reduced ability to scavenge free radicals and thus a lack of effective protection against oxidative stress in patients with adrenal tumors. Both plasma and urine redox biomarkers can be used to assess systemic antioxidant status in adrenal tumor patients.

Safety and Efficacy of Indocyanine Green in Colorectal Cancer Surgery: A Systematic Review and Meta-Analysis of 11,047 Patients.

Despite the technological advances and improved surgical skills, the incidence of anastomotic leakage following colorectal cancer surgery still ranges from 4% to 19%. Therefore, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of indocyanine green (ICG) use in colorectal cancer surgery. An online search of the Embase, MEDLINE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases (from inception to 10 November 2021) was performed, in addition to manual screening. Thirty-two studies involving 11,047 patients were considered eligible for the meta-analysis. The anastomotic leak rate in the ICG and non-ICG groups varied and amounted to 3.7% vs. 7.6%, respectively (RR = 0.46; 95% CI: 0.39-0.56; p < 0.001). The rate in randomized controlled trials (RCTs) was 8.1% in the ICG group compared with 12.1% in the non-ICG group (RR = 0.67; 95% CI: 0.46-0.98; p = 0.04). In non-RCTs, it equaled 3.1% vs. 7.3%, respectively (RR = 0.43; 95% CI: 0.35-0.52; p < 0.001). Although the publications encompassed in our meta-analysis present different patients, with different factors influencing the results, a pooled analysis revealed a lower incidence of anastomotic leak in cases with ICG use. There are several other convincing advantages: safety, simplicity, and short time of the method adjustment. The presented meta-analysis indicates ICG perfusion assessment as a tool worth considering to decrease the rate of complications following colorectal surgery-valuable in the context of other, well-known risk factors.

Liver allograft antibody-mediated rejection with demonstration of sinusoidal C4d staining and circulating donor-specific antibodies.

The importance of antibody-mediated rejection (AMR) in ABO-compatible liver transplantation is controversial. Here we report a prospective series of liver recipients with a preoperative positive crossmatch. To establish the diagnosis of AMR in liver recipients, the criteria described for kidney allografts were adopted. In approximately 10% of 197 liver transplants, we observed a positive T and B cell flow crossmatch before transplantation. Fifteen of 19 patients converted to negative crossmatches early after transplantation and displayed normal liver function while they were on routine immunosuppression. Four patients maintained positive crossmatches. Three of the 4 met the criteria for AMR and showed evidence of graft dysfunction, the presence of donor-specific antibodies (DSAs), morphological tissue destruction with positive C4d linear staining on the graft sinusoidal endothelium, and improved function with attempts to eliminate DSAs. A persistently positive crossmatch after liver transplantation may lead to early, severe AMR and liver failure. C4d staining in the liver sinusoidal endothelium should alert one to the possibility of AMR. In our experience, patients with a positive crossmatch should have it repeated at 2 weeks and, if it is positive, again at 3 to 5 weeks. Recipients with an unknown preoperative crossmatch who develop early cholestasis of unclear etiology should be crossmatched or tested for the presence of DSAs to evaluate for AMR.

The influence of nonalcoholic fatty liver disease and its associated comorbidities on liver transplant outcomes.

GOALS: To define the influence of nonalcoholic fatty liver disease (NAFLD) and its associated comorbidities on liver transplant outcomes. BACKGROUND: NAFLD cirrhosis is an increasing indication for transplant. The transplant outcomes of NAFLD patients with metabolic syndrome comorbidities remain unclear. STUDY: We examined a single center, retrospective cohort between 2004 and 2007 to determine transplant mortality for NAFLD and non-NAFLD patients accounting for the possible independent effects of diabetes, hypertension, obesity, and hyperlipidemia. The primary outcomes were 30-day, 1-year, and 3-year all-cause mortality. Cox proportional hazard ratios were determined controlling for various recipient and donor covariates. RESULTS: In our study, of 118 liver transplants, 18% were performed for NAFLD cirrhosis. Adjusted hazard ratios for death for NAFLD compared with non-NAFLD patients at 30 days, 1 year, and 3 years were 8.96 (1.06, 75.8), 1.49 (0.38, 5.81), and 1.05 (0.29, 3.78), respectively. Compared with nondiabetic patients, diabetic patients had hazard ratios at 30 days, 1 year, and 3 years of 2.02 (0.31, 12.9), 2.82 (0.94, 8.47), 3.58 (1.32, 9.71), respectively. Obesity, hypertension, and hyperlipidemia did not have a significant impact on posttransplant mortality. CONCLUSIONS: We conclude that NAFLD increases 30-day transplant mortality whereas diabetes increases 3-year mortality. Future work should determine the strategies to decrease perioperative mortality among NAFLD patients and ways to improve long-term transplant survival among diabetics.

Focal fat masquerading as malignancy in the liver graft of a post-transplant patient.

BACKGROUND AND AIMS: Liver failure from non-alcoholic fatty liver disease (NAFLD) is an increasing indication for liver transplant and recurrence of fatty liver in transplanted grafts has been documented. Herein is described an atypical recurrence of steatosis as a de novo focal fatty lesion that mimicked a more ominous cancerous lesion. This presentation of recurrent NAFLD has not previously been described in the literature. METHODS: Chart review. RESULTS: Biopsy of an atypical lesion was found to be focal fat with surrounding steatohepatitis. CONCLUSIONS: Non-alcoholic fatty liver disease may recur after liver transplant and manifest as a focal fatty lesion. It is important to catalogue the atypical presentations of the increasingly common NAFLD developing in transplanted livers.