Development of a portable abdominal normothermic regional perfusion (A-NRP) program in the United States.

In situ abdominal normothermic regional perfusion (A-NRP) has been used for liver transplantation (LT) with donation after circulatory death (DCD) liver grafts in Europe with excellent results; however, adoption of A-NRP in the United States has been lacking. The current report describes the implementation and results of a portable, self-reliant A-NRP program in the United States. Isolated abdominal in situ perfusion with an extracorporeal circuit was achieved through cannulation in the abdomen or femoral vessels and inflation of a supraceliac aortic balloon and cross-clamp. The Quantum Transport System by Spectrum was used. The decision to use livers for LT was made through an assessment of perfusate lactate (q15min). From May to November 2022, 14 A-NRP donation after circulatory death procurements were performed by our abdominal transplant team (N = 11 LT, N = 20 kidney transplants, and 1 kidney-pancreas transplant). The median A-NRP run time was 68 minutes. None of the LT recipients had post-reperfusion syndrome, nor were there any cases of primary nonfunction. All livers were functioning well at the time of maximal follow-up with zero cases of ischemic cholangiopathy. The current report describes the feasibility of a portable A-NRP program that can be used in the United States. Excellent short-term post-transplant results were achieved with both livers and kidneys procured from A-NRP.

RECURRENT FLOATERS AFTER LIMITED VITRECTOMY FOR VISION DEGRADING MYODESOPSIA.

PURPOSE: Limited vitrectomy improves vision degrading myodesopsia, but the incidence of recurrent floaters postoperatively is not known. We studied patients with recurrent central floaters using ultrasonography and contrast sensitivity (CS) testing to characterize this subgroup and identify the clinical profile of patients at risk of recurrent floaters. METHODS: A total of 286 eyes (203 patients, 60.6 ± 12.9 years) undergoing limited vitrectomy for vision degrading myodesopsia were studied retrospectively. Sutureless 25G vitrectomy was performed without intentional surgical posterior vitreous detachment (PVD) induction. CS (Freiburg Acuity Contrast test: Weber index, %W) and vitreous echodensity (quantitative ultrasonography) were assessed prospectively. RESULTS: No eyes (0/179) with preoperative PVD experienced new floaters. Recurrent central floaters occurred in 14/99 eyes (14.1%) without complete preoperative PVD (mean follow-up = 39 months vs. 31 months in 85 eyes without recurrent floaters). Ultrasonography identified new-onset PVD in all 14 (100%) recurrent cases. Young (younger than 52 years; 71.4%), myopic (≥-3D; 85.7%), phakic (100%) men (92.9%) predominated. Reoperation was elected by 11 patients, who had partial PVD preoperatively in 5/11 (45.5%). At study entry, CS was degraded (3.55 ± 1.79 %W) but improved postoperatively by 45.6% (1.93 ± 0.86 %W, P = 0.033), while vitreous echodensity reduced by 86.6% ( P = 0.016). New-onset PVD postoperatively degraded CS anew, by 49.4% (3.28 ± 0.96 %W; P = 0.009) in patients electing reoperation. Repeat vitrectomy normalized CS to 2.00 ± 0.74%W ( P = 0.018). CONCLUSION: Recurrent floaters after limited vitrectomy for vision degrading myodesopsia are caused by new-onset PVD, with younger age, male sex, myopia, and phakic status as risk factors. Inducing surgical PVD at the primary operation should be considered in these select patients to mitigate recurrent floaters.

Percutaneous direct pancreatic duct intervention in management of pancreatic fistulas: a primary treatment or temporizing therapy to prepare for elective surgery.

BACKGROUND: This study evaluates preliminary results of image-guided percutaneous direct pancreatic duct intervention in the management of pancreatic fistula after surgery or pancreatitis when initially ineligible for surgical or endoscopic therapy. METHODS: Between 2001 and 2018 the medical records of all patients that underwent percutaneous pancreatic duct intervention for radiographically confirmed pancreatic fistula initially ineligible for surgical or endoscopic repair were reviewed for demographics, clinical history, procedure details, adverse events, procedure related imaging and laboratory results, ability to directly catheterized the main pancreatic duct, and whether desired clinical objectives were met. RESULTS: In 10 of 11patients (6 male and 5 female with mean age 60.5, range 39-89) percutaneous pancreatic duct cannulation was possible. The 10 duct interventions included direct ductal suction drainage in 7, percutaneous duct closure in 3 and stent placement in 1. Pancreatic fistulas closed in 7 of 10, 2 were temporized until elective surgery, and 1 palliated until death from malignancy. The single patient with failed duct cannulation resolved the fistula with prolonged catheter drainage of the peri-pancreatic cavity. There were no major adverse events related to intervention. CONCLUSION: In patients with pancreatic fistulas initially ineligible for endoscopic therapy or elective surgery, direct percutaneous pancreatic duct interventions are possible, can achieve improvement without major morbidity or mortality, and can improve and maintain the medical condition of patients in preparation for definitive surgery.

Enhanced and controlled chromatin extraction from FFPE tissues and the application to ChIP-seq.

BACKGROUND: Epigenetic dysregulation is involved in the etiology and progression of various human diseases. Formalin-fixed paraffin-embedded (FFPE) samples represent the gold standard for archiving pathology samples, and thus FFPE samples are a major resource of samples in clinical research. However, chromatin-based epigenetic assays in the clinical settings are limited to fresh or frozen samples, and are hampered by low chromatin yield in FFPE samples due to the lack of a reliable and efficient chromatin preparation method. Here, we introduce a new chromatin extraction method from FFPE tissues (Chrom-EX PE) for chromatin-based epigenetic assays. RESULTS: During rehydration of FFPE tissues, applying a tissue-level cross-link reversal into the deparaffinized tissue at 65 °C dramatically increased chromatin yield in the soluble fraction. The resulting chromatin is compatible with targeted ChIP-qPCR and genome-wide ChIP-seq approaches. The chromatin prepared by Chrom-EX PE showed a gradual fragmentation pattern with varying incubation temperature. At temperatures below 37 °C, the majority of soluble chromatin is over 1 kb. The soluble chromatin prepared in the range of 45-60 °C showed a typical nucleosomal pattern. And the majority of chromatin prepared at 65 °C is close to mononucleosomal size. These observations indicate that chromatin preparation from FFPE samples can be controlled for downstream chromatin-based epigenetic assays. CONCLUSIONS: This study provided a new method that achieves efficient extraction of high-quality chromatin suitable for chromatin-based epigenetic assays with less damage on chromatin. This approach may provide a way to circumvent the over-fixed nature of FFPE tissues for future technology development.

Evolving Role of Liver Transplantation in Elderly Recipients.

The need for liver transplantation (LT) among older patients is increasing, but the role of LT in the elderly (≥70 years) is not well defined. We retrospectively reviewed all primary LTs from 1998 through 2016 at our center. Survival and associated risk factors were analyzed with Cox regression and Kaplan-Meier methods for LT recipients in 3 age groups: <60, 60-69, and ≥70 years. Among 2281 LT recipients, the median age was 56 years (range, 15-80 years), and 162 were aged ≥70 years. The estimated 5- and 10-year patient survival probabilities for elderly LT recipients were lower (70.8% and 43.6%) than for recipients aged 60-69 years (77.2% and 64.6%) and <60 years (80.7% and 67.6%). Patient and graft survival rates associated with LT improved over time from the pre-Model for End-Stage Liver Disease era to Share 15, pre-Share 35, and Share 35 for the cohort overall (P < 0.001), but rates remained relatively stable in septuagenarians throughout the study periods (all P > 0.45). There was no incremental negative effect of age at LT among elderly patients aged 70-75 years (log-rank P = 0.32). Among elderly LT recipients, greater requirement for packed red blood cells and longer warm ischemia times were significantly associated with decreased survival (P < 0.05). Survival of LT recipients, regardless of age, markedly surpassed that of patients who were denied LT, but it was persistently 20%-30% lower than the expected survival of the general US population (P < 0.001). With the aging of the population, select older patients with end-stage liver diseases can benefit from LT, which largely restores their expected life spans.

Assessment of Vitreous Structure and Visual Function after Neodymium:Yttrium-Aluminum-Garnet Laser Vitreolysis.

PURPOSE: Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser treatment is performed on vitreous floaters, but studies of structural and functional effects with objective outcome measures are lacking. This study evaluated Nd:YAG laser effects by comparing participants with vitreous floaters who previously underwent laser treatment with untreated control participants and healthy persons without vitreous floaters using quantitative ultrasonography to evaluate vitreous structure and by measuring visual acuity and contrast sensitivity function to assess vision. DESIGN: Retrospective, comparative study. PARTICIPANTS: One eye was enrolled for each of 132 participants: 35 control participants without vitreous floaters, 59 participants with untreated vitreous floaters, and 38 participants with vitreous floaters previously Nd:YAG-treated. Of these, 25 were dissatisfied and sought vitrectomy; 13 were satisfied with observation. METHODS: The 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-39) to assess participant visual well-being, quantitative ultrasonography (QUS) to measure vitreous echodensity, and best-corrected visual acuity (BCVA) and contrast sensitivity function (CSF) to evaluate vision. MAIN OUTCOME MEASURES: Results of NEI-VFQ-39, QUS, BCVA, and CSF. RESULTS: Compared with control participants without vitreous floaters, participants with untreated vitreous floaters showed worse NEI-VFQ-39 results, 57% greater vitreous echodensity, and significant (130%) CSF degradation (P < 0.001 for each). Compared with untreated eyes with vitreous floaters, Nd:YAG-treated eyes had 23% less vitreous echodensity (P < 0.001), but no differences in NEI-VFQ-39 (P = 0.51), BCVA (P = 0.42), and CSF (P = 0.17) results. Of 38 participants with vitreous floaters who previously were treated with Nd:YAG, 25 were dissatisfied and seeking vitrectomy, whereas 13 were satisfied with observation. Participants seeking vitrectomy showed 24% greater vitreous echodensity (P = 0.018) and 52% worse CSF (P = 0.006). Multivariate linear regression models confirmed these findings. CONCLUSIONS: As a group, participants previously treated with Nd:YAG laser for bothersome vitreous floaters showed less dense vitreous, but similar visual function as untreated control participants with vitreous floaters. Because some treated eyes showed less dense vitreous and better visual function than those of untreated control participants, a prospective randomized study of Nd:YAG laser treatment of vitreous is warranted, using uniform laser treatment parameters and objective quantitative outcome measures.

Sexual dimorphism in the incidence of human cancers.

BACKGROUND: Sex differences in the incidences of cancers become a critical issue in both cancer research and the development of precision medicine. However, details in these differences have not been well reported. We provide a comprehensive analysis of sexual dimorphism in human cancers. METHODS: We analyzed four sets of cancer incidence data from the SEER (USA, 1975-2015), from the Cancer Registry at Mayo Clinic (1970-2015), from Sweden (1970-2015), and from the World Cancer Report in 2012. RESULTS: We found that all human cancers had statistically significant sexual dimorphism with male dominance in the United States and mostly significant in the Mayo Clinic, Sweden, and the world data, except for thyroid cancer, which is female-dominant. CONCLUSIONS: Sexual dimorphism is a clear but mostly neglected phenotype for most human cancers regarding the clinical practice of cancer. We expect that our study will facilitate the mechanistic studies of sexual dimorphism in human cancers. We believe that fully addressing the mechanisms of sexual dimorphism in human cancers will greatly benefit current development of individualized precision medicine beginning from the sex-specific diagnosis, prognosis, and treatment.

GABA, γ-Aminobutyric Acid, Protects Against Severe Liver Injury.

BACKGROUND: Acute liver failure (ALF) from severe acute liver injury is a critical condition associated with high mortality. The purpose of this study was to investigate the impact of preemptive administration of γ-aminobutyric acid (GABA) on hepatic injury and survival outcomes in mice with experimentally induced ALF. MATERIALS AND METHODS: To induce ALF, C57BL/6NHsd mice were administered GABA, saline, or nothing for 7 d, followed by intraperitoneal administration of 500 µg of tumor necrosis factor α and 20 mg of D-galactosamine. The study mice were humanely euthanized 4-5 h after ALF was induced or observed for survival. Proteins present in the blood samples and liver tissue from the euthanized mice were analyzed using Western blot and immunohistochemical and histopathologic analyses. For inhibition studies, we administered the STAT3-specific inhibitor, NSC74859, 90 min before ALF induction. RESULTS: We found that GABA-treated mice had substantial attenuation of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive hepatocytes and hepatocellular necrosis, decreased caspase-3, H2AX, and p38 MAPK protein levels and increased expressions of Jak2, STAT3, Bcl-2, and Mn-SOD, with improved mitochondrial integrity. The reduced apoptotic proteins led to a significantly prolonged survival after ALF induction in GABA-treated mice. The STAT3-specific inhibitor NSC74859 eliminated the survival advantage in GABA-treated mice with ALF, indicating the involvement of the STAT3 pathway in GABA-induced reduction in apoptosis. CONCLUSIONS: Our results showed that preemptive treatment with GABA protected against severe acute liver injury in mice via GABA-mediated STAT3 signaling. Preemptive administration of GABA may be a useful approach to optimize marginal donor livers before transplantation.

Visualization of Hepatocellular Regeneration in Mice After Partial Hepatectomy.

BACKGROUND: Although hepatocellular regeneration is the cornerstone of liver homeostasis, current techniques for assessing such regeneration are limited. A method for visualizing the regeneration process would provide a means for advanced studies. Therefore, we examined the possibility of using fluorescence ubiquination-based cell cycle indicator (Fucci) mice for direct visualization of hepatocellular regeneration. MATERIALS AND METHODS: We performed a two-thirds partial hepatectomy in conventional and Fucci mice. Fucci animals have orange Cdt1 expressed in the G1 phase and green Geminin expressed in S/G2/M phases. Regenerating livers were procured daily for 7 d. Immunohistochemical staining was performed for proliferative Ki67 and mitotic pHH3 serine 10 (pHH3) markers on formalin-fixed, paraffin-embedded tissue sections from conventional mice. The orange Cdt1 and green Geminin fluorescence indicative of the G1 and S/G2/M phases, respectively, were assessed in liver tissues, in vivo and ex vivo, with two-photon laser scanning microscopy. RESULTS: Immunostaining with Ki67 and pHH3 revealed a typical profile of hepatocellular regeneration after hepatectomy in conventional mice, although immunostaining required more than a week to process. In contrast, hepatocellular regeneration could be visualized with two-photon microscopy within a few hours in regenerating livers of the Fucci mice. Only orange G1 hepatocytes were seen in the baseline liver specimens; however, multiple bright green and yellow hepatocytes were seen 48 h after hepatectomy, indicating active hepatocytes in the S/G2/M phases of the cell cycle. CONCLUSIONS: Hepatocellular regeneration is readily visualized in regenerating livers of Fucci mice. The Fucci model is an exciting tool for advanced studies of hepatocellular and liver regeneration.

STRUCTURAL AND FUNCTIONAL CHARACTERISTICS OF LAMELLAR MACULAR HOLES.

PURPOSE: Lamellar macular holes (LMHs) can been subdivided into tractional and degenerative subtypes. This cross-sectional cohort study compared structural and functional characteristics in these subtypes hypothesizing that tractional LMH has a higher prevalence of vitreopapillary adhesion and tangential traction (macular pucker), whereas degenerative LMH has more ellipsoid zone disruption and worse vision, measured three different ways. METHODS: Tractional LMH (n = 22) and degenerative LMH (n = 15) were distinguished by optical coherence tomography criteria. Separate spectral domain optical coherence tomography scanning of the macula and optic disk was performed. Visual acuity, contrast sensitivity function (Weber Index, %W), and the degree of visual distortions (3-dimensional threshold Amsler grid; % volume lost [%VL]) were quantified. RESULTS: Vitreopapillary adhesion was present in 14/22 (64%) tractional, but in only 3/15 (20%) degenerative LMH (P = 0.006). Macular pucker was present in 19/22 (86%) tractional, but in only 8/15 (53%) degenerative LMH (P = 0.011). Ellipsoid zone disruption was present in 13/15 (87%) degenerative, but in only 2/22 (9%) tractional LMH (P = 0.0001). Visual acuity was better in tractional than degenerative LMH (P = 0.006), as was contrast sensitivity function (tractional = 3.44 ± 1.07 %W, degenerative = 4.66 ± 1.73 %W; P = 0.015). Visual distortions were less in tractional (0.33 ± 0.61 %VL) than in degenerative (0.85 ± 0.68 %VL) LMH (P = 0.014). CONCLUSION: Structure and visual function differ significantly in subtypes of LMH. Tractional LMH has 3-fold higher prevalence of vitreopapillary adhesion and 2-fold higher prevalence of macular pucker. Degenerative LMH has 9-fold more ellipsoid zone disruption, worse visual acuity and contrast sensitivity function, and 3-fold more distortions. Thus, outer retinal integrity seems more closely correlated with vision than anterior structural abnormalities in LMH.

Liver transplantation for intrahepatic cholangiocarcinoma.

Although hepatocellular carcinoma (HCC) has become a common indication for liver transplantation (LT), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) are historically contraindicated due to their aggressive behavior. On the basis of recent experiences, some groups have proposed a clinical trial investigating the role of LT for patients with early cholangiocarcinoma (CCA), defined as a single lesion ≤ 2 cm. The purpose of this study is to assess the clinicopathologic features and outcomes following LT for patients who were initially diagnosed with HCC and subsequently found to have either ICC or cHCC-CCA on explant. Patients with the diagnosis of primary liver cancer (PLC) after LT from a single center were retrospectively reviewed. Outcomes for patients with early CCA were compared with patients with HCC within Milan criteria (MC). Out of 618 patients transplanted with PLC, 44 patients were found to have CCA on explant. On the basis of preoperative imaging, 12 patients met criteria for early CCA and were compared with 319 patients who had HCC within MC. The 1- and 5-year overall survival for early CCA versus HCC was 63.6% versus 90.0% and 63.6% versus 70.3% (log-rank, P = 0.25), respectively. Overall recurrence was 33.3% for early CCA versus 11% for HCC. On explant the patients with CCA were more likely understaged with higher tumor grade and vascular invasion. In conclusion, patients with CCA present a diagnostic challenge, which often leads to the finding of more aggressive lesions on explant after LT, higher recurrence rates, and worse post-LT survival. Careful consideration of this diagnostic conundrum needs to be made before a clinical trial is undertaken. Liver Transplantation 24 634-644 2018 AASLD.

Hepatic artery stenosis after liver transplant: Donation after cardiac death donor vs donation after brain death donor grafts.

BACKGROUND: Hepatic artery stenosis (HAS) after liver transplant (LT) is a source of significant morbidity. Some reports have suggested higher arterial complications in patients who receive donation after cardiac death (DCD) livers. METHODS: A total of 2860 consecutive LT were reviewed from a prospectively collected database. All angiograms performed in LT recipients were reviewed and primary patency rates determined by need for further intervention or graft loss due to HAT. RESULTS: Hepatic artery stenosis was seen in 4.6% of DCD and donation after brain death (DBD) recipients. Recipient male gender, age at transplant, complex donor hepatic artery anatomy, and prolonged operative time were all associated with HAS, but not DCD status. While HAS in recipients of DCD grafts required more stents (1.7% vs 0.6%, P = 0.04) and had worse primary patency rates (logrank, P = 0.02), outcomes as defined by HAT, patient and graft survival were not significantly different between the recipients of DCD or DBD grafts. CONCLUSION: We observed no significant difference in the incidence of hepatic artery complications, patient survival, or graft survival in recipients of DCD or DBD grafts. However, HAS in DCD recipients had worse primary patency and a higher need for stent placement.

The effects of aging vitreous on contrast sensitivity function.

PURPOSE: Contrast sensitivity function (CSF) declines with age. When unassociated with cataracts, this is hypothesized to be due to macular ganglion cell complex (GCC) thinning. However, other studies found associations with increased vitreous echodensity and posterior vitreous detachment (PVD). We investigate the relationship between CSF, vitreous echodensity, PVD, and GCC thickness as related to age in the same subjects. METHODS: Age, CSF (Weber index: %W), vitreous echodensity (quantitative ultrasonography [QUS]), lens status (phakia or pseudophakia), best-corrected visual acuity (BCVA), and GCC thickness (SD-OCT) were evaluated in 57 eyes of 57 subjects with (n = 32, mean age = 62 years) and without (n = 25, mean age = 44 years) PVD (P < 0.001). A multivariate linear regression analysis was performed to assess the effects of independent variables on CSF. RESULTS: CSF was 51.2% worse in eyes with PVD (2.98 ± 0.31 %W) compared to no PVD (1.97 ± 0.24 %W; P < 0.001). QUS was 55.8% greater in eyes with PVD than those without (P < 0.001). Among all subjects, PVD status, vitreous echodensity, and age were the only independent variables demonstrating significant effects on CSF. Lens status, BCVA, and GCC thickness did not demonstrate association with CSF. CONCLUSIONS: PVD, vitreous echodensity, and age are determinants of CSF. PVD and increased vitreous echodensity are each associated with diminished CSF, independent of age. Thus, in the absence of GCC thinning and cataracts, vitreous changes may be a cause of decreased CSF with age.

Comparison of longterm outcomes and quality of life in recipients of donation after cardiac death liver grafts with a propensity-matched cohort.

The use of liver grafts from donation after cardiac death (DCD) has been limited due to the increased rate of graft failure, mostly related to ischemic cholangiopathy (IC). It is our hypothesis that longterm outcomes and quality of life (QOL) similar to patients undergoing liver transplantation (LT) with donation after brain death (DBD) can be achieved. Clinical outcomes of all patients undergoing DCD LT (n = 300) between 1998 and 2015 were compared with a propensity score-matched cohort of patients undergoing DBD LT (n = 300). Patients were contacted for a follow-up questionnaire and short-form (SF)-12 QOL Survey administration. Median follow-up was >5 years. Graft survival at 1-, 3-, and 5-years was 83.8%, 75.5%, and 70.1% in the DCD LT group and 88.4%, 80.3%, and 73.9% in the DBD LT group (P = 0.27). Patient survival at 1-, 3-, and 5-years was 92.3%, 86.1%, and 80.3% in the DCD LT group and 92.3%, 85.1%, and 79.5% in the DBD LT group (P = 0.81). IC developed in 11.7% and 2% of patients in the DCD LT group and DBD LT group, respectively (P < 0.001). DCD LT recipients who developed IC had inferior graft survival compared with both the DCD non-IC group (P < 0.001) and the DBD LT group (P < 0.001); no difference in graft survival was observed between the DCD non-IC group and the DBD LT group (P = 0.50). Physical and Mental Composite Scores on the SF-12 QOL questionnaire were similar between the DCD LT and DBD LT groups (44.0 versus 45.4; P = 0.34 and 51.9 versus 52.2; P = 0.83), respectively. Similar longterm survival and QOL scores can be achieved between DCD LT and DBD LT. Prevention of IC in DCD LT yields excellent graft and patient survival with virtually no difference compared with DBD LT. Liver Transplantation 23 342-351 2017 AASLD.

Liver Transplantation for Hepatocellular Carcinoma: Impact of Wait Time at a Single Center.

INTRODUCTION AND AIM: Liver transplantation (LT) provides durable survival for hepatocellular carcinoma (HCC). However, there is continuing debate concerning the impact of wait time and acceptable tumor burden on outcomes after LT. We sought to review outcomes of LT for HCC at a single, large U.S. center, examining the influence of wait time on post-LT outcomes. MATERIAL AND METHODS: We reviewed LT for HCC at Mayo Clinic in Florida from 1/1/2003 until 6/30/2014. Follow up was updated through 8/1/ 2015. RESULTS: From 2003-2014, 978 patients were referred for management of HCC. 376 patients were transplanted for presumed HCC within Milan criteria, and the results of these 376 cases were analyzed. The median diagnosis to LT time was 183 days (8 - 4,337), and median transplant list wait time was 62 days (0 - 1815). There was no statistical difference in recurrence-free or overall survival for those with wait time of less than or greater than 180 days from diagnosis of HCC to LT. The most important predictor of long term survival after LT was HCC recurrence (HR: 18.61, p < 0.001). Recurrences of HCC as well as survival were predicted by factors related to tumor biology, including histopathological grade, vascular invasion, and pre-LT serum alpha-fetoprotein levels. Disease recurrence occurred in 13%. The overall 5-year patient survival was 65.8%, while the probability of 5-year recurrence-free survival was 62.2%. CONCLUSIONS: In this large, single-center experience with long-term data, factors of tumor biology, but not a longer wait time, were associated with recurrence-free and overall survival.

Outcomes of liver transplantation with liver grafts from pediatric donors used in adult recipients.

Although there is an agreement that liver grafts from pediatric donors (PDs) should ideally be used for pediatric patients, there remain situations when these grafts are turned down for pediatric recipients and are then offered to adult recipients. The present study aimed to investigate the outcomes of using these grafts for liver transplantation (LT) in adult patients. Data from all patients undergoing LT between 2002 and 2014 were obtained from the United Network for Organ Sharing Standard Analysis and Research file. Adult recipients undergoing LT were divided into 2 groups: those receiving a pediatric liver graft (pediatric-to-adult group) and those receiving a liver graft from adult donors (adult-to-adult group). A separate subgroup analysis comparing the PDs used for adult recipients and those used for pediatric recipients was also performed. Patient and graft survival were not significantly different between pediatric-to-adult and adult-to-adult groups (P = 0.08 and P = 0.21, respectively). Hepatic artery thrombosis as the cause for graft loss was higher in the pediatric-to-adult group (3.6%) than the adult-to-adult group (1.9%; P < 0.001). A subanalysis looking at the pediatric-to-adult group found that patients with a predicted graft-to-recipient weight ratio (GRWR) < 0.8 had a higher 90-day graft loss rate than those with a GRWR ≥ 0.8 (39% versus 9%; P < 0.001). PDs used for adult recipients had a higher proportion of donors with elevated aspartate aminotransferase/alanine aminotransferase (20% vs. 12%; P < 0.001), elevated creatinine (11% vs. 4%; P < 0.001), donation after cardiac death donors (12% vs. 0.9%; P < 0.001), and were hepatitis B virus core positive (1% vs. 0.3%; P = 0.002) than PDs used for pediatric recipients. In conclusion, acceptable patient and graft survival can be achieved with the use of pediatric liver grafts in adult recipients, when these grafts have been determined to be inappropriate for usage in the pediatric population. Liver Transplantation 22 1099-1106 2016 AASLD.

Quantifying Visual Dysfunction and the Response to Surgery in Macular Pucker.

PURPOSE: To measure the effects of macular pucker (MP) on macular structure and quantify function by measuring visual acuity (VA), contrast sensitivity (CS), and distortions. The effects of surgery were quantitatively evaluated using these measures. DESIGN: Prospective, comparative case series. PARTICIPANTS: Fifty-three patients with unilateral MP and normal fellow eyes: 24 operated MP subjects, 17 unoperated controls, and 12 reproducibility subjects. METHODS: Posterior vitreous detachment was diagnosed by ultrasound and ellipsoid zone disruption (EZD) was determined by OCT, which also measured macular thickness and volume. Vision was assessed, by measuring VA (logMAR) and CS (Freiburg acuity contrast testing: Weber index, %W). A visual distortions index (%DI) was calculated using 3-dimensional threshold Amsler grid testing. Comparisons to controls were performed before surgery and at 1, 3, 6, and 12 months after vitrectomy/membrane peel without chromodissection. MAIN OUTCOME MEASURES: Posterior vitreous detachment (ultrasound), EZD (OCT), macular thickness and volume (OCT), VA (logMAR), CS (%W), distortions (%DI). RESULTS: Posterior vitreous detachment was present in 90% of MP eyes, but only 50% of fellow eyes (P < 0.001). All structural and functional indices were worse (28% to 5-fold) in the 24 operated MP eyes than the 17 unoperated MP eyes (P < 0.001). Before surgery, EZD was present in 33% of operated MP eyes but none of the unoperated MP eyes (P < 0.02). The macula was thicker (514±85 µm vs. 257±59 µm; P < 0.001) with greater volume (3.22±0.56 µl vs. 2.14±0.22 µl; P < 0.001) in operated MP eyes than normal fellow eyes. Before surgery, MP eyes had VA = 0.53 logMAR (Snellen equivalent, 20/67) vs. controls = 0.21 (20/32); P < 0.001; CS was 8.61±5.36 %W vs. controls = 3.71±1.47 %W (P < 0.001); and distortions were 7.61±12.6 %DI vs. controls = 0.13±0.61 %DI (P < 0.001). EZD was associated with worse VA (P < 0.01) and CS (P < 0.03) before and after surgery. Each outcome measure improved progressively at 1, 3, 6, and 12 months after surgery, but only %DI and macular volume normalized. CONCLUSIONS: These quantitative measures characterize the impact of MP on macular structure and function. All indices improved after surgery, but only distortions and macular volume normalized. Contrast sensitivity measurements and quantification of distortions can objectively assess visual dysfunction in MP and may be useful outcome measures of therapy.