Admix-kit: an integrated toolkit and pipeline for genetic analyses of admixed populations.

SUMMARY: Admixed populations, with their unique and diverse genetic backgrounds, are often underrepresented in genetic studies. This oversight not only limits our understanding but also exacerbates existing health disparities. One major barrier has been the lack of efficient tools tailored for the special challenges of genetic studies of admixed populations. Here, we present admix-kit, an integrated toolkit and pipeline for genetic analyses of admixed populations. Admix-kit implements a suite of methods to facilitate genotype and phenotype simulation, association testing, genetic architecture inference, and polygenic scoring in admixed populations. AVAILABILITY AND IMPLEMENTATION: Admix-kit package is open-source and available at https://github.com/KangchengHou/admix-kit. Additionally, users can use the pipeline designed for admixed genotype simulation available at https://github.com/UW-GAC/admix-kit_workflow.

Assessing the degree of hepatic ischemia-reperfusion injury using physiologically based pharmacokinetic modeling of sodium fluorescein disposition in ex vivo machine-perfused livers.

Ischemia-reperfusion injury (IRI) is an intrinsic risk associated with liver transplantation. Ex vivo hepatic machine perfusion (MP) is an emerging organ preservation technique that can mitigate IRI, especially in livers subjected to prolonged warm ischemia time (WIT). However, a method to quantify the biological response to WIT during MP has not been established. Previous studies used physiologically based pharmacokinetic (PBPK) modeling to demonstrate that a decrease in hepatic transport and biliary excretion of the tracer molecule sodium fluorescein (SF) could correlate with increasing WIT in situ. Furthermore, these studies proposed intracellular sequestration of the hepatocyte canalicular membrane transporter multidrug resistance-associated protein 2 (MRP2) leading to decreased MRP2 activity (maximal transport velocity; Vmax) as the potential mechanism for decreased biliary SF excretion. We adapted an extant PBPK model to account for ex vivo hepatic MP and fit a six-parameter version of this model to control time-course measurements of SF in MP perfusate and bile. We then identified parameters whose values were likely insensitive to changes in WIT and fixed them to generate a reduced model with only three unknown parameters. Finally, we fit the reduced model to each individual biological replicate SF time course with differing WIT, found the mean estimated value for each parameter, and compared them using a one-way ANOVA. We demonstrated that there was a significant decrease in the estimated value of Vmax for MRP2 at the 30-min WIT. These studies provide the foundation for future studies investigating real-time assessment of liver viability during ex vivo MP.NEW & NOTEWORTHY We developed a computational model of sodium fluorescein (SF) biliary excretion in ex vivo machine perfusion and used this model to assess changes in model parameters associated with the activity of MRP2, a hepatocyte membrane transporter, in response to increasing warm ischemia time. We found a significant decrease in the parameter value describing MRP2 activity, consistent with a role of decreased MRP2 function in ischemia-reperfusion injury leading to decreased secretion of SF into bile.

The power of TOPMed imputation for the discovery of Latino-enriched rare variants associated with type 2 diabetes.

AIMS/HYPOTHESIS: The Latino population has been systematically underrepresented in large-scale genetic analyses, and previous studies have relied on the imputation of ungenotyped variants based on the 1000 Genomes (1000G) imputation panel, which results in suboptimal capture of low-frequency or Latino-enriched variants. The National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) released the largest multi-ancestry genotype reference panel representing a unique opportunity to analyse rare genetic variations in the Latino population. We hypothesise that a more comprehensive analysis of low/rare variation using the TOPMed panel would improve our knowledge of the genetics of type 2 diabetes in the Latino population. METHODS: We evaluated the TOPMed imputation performance using genotyping array and whole-exome sequence data in six Latino cohorts. To evaluate the ability of TOPMed imputation to increase the number of identified loci, we performed a Latino type 2 diabetes genome-wide association study (GWAS) meta-analysis in 8150 individuals with type 2 diabetes and 10,735 control individuals and replicated the results in six additional cohorts including whole-genome sequence data from the All of Us cohort. RESULTS: Compared with imputation with 1000G, the TOPMed panel improved the identification of rare and low-frequency variants. We identified 26 genome-wide significant signals including a novel variant (minor allele frequency 1.7%; OR 1.37, p=3.4 × 10-9). A Latino-tailored polygenic score constructed from our data and GWAS data from East Asian and European populations improved the prediction accuracy in a Latino target dataset, explaining up to 7.6% of the type 2 diabetes risk variance. CONCLUSIONS/INTERPRETATION: Our results demonstrate the utility of TOPMed imputation for identifying low-frequency variants in understudied populations, leading to the discovery of novel disease associations and the improvement of polygenic scores. DATA AVAILABILITY: Full summary statistics are available through the Common Metabolic Diseases Knowledge Portal ( https://t2d.hugeamp.org/downloads.html ) and through the GWAS catalog ( https://www.ebi.ac.uk/gwas/ , accession ID: GCST90255648). Polygenic score (PS) weights for each ancestry are available via the PGS catalog ( https://www.pgscatalog.org , publication ID: PGP000445, scores IDs: PGS003443, PGS003444 and PGS003445).

A Double-Blind, Randomized, Placebo-Controlled, Phase II Clinical Study To Evaluate the Efficacy and Safety of Camostat Mesylate (DWJ1248) in Adult Patients with Mild to Moderate COVID-19.

Although several antiviral agents have become available for coronavirus disease 2019 (COVID-19) treatment, oral drugs are still limited. Camostat mesylate, an orally bioavailable serine protease inhibitor, has been used to treat chronic pancreatitis in South Korea, and it has an in vitro inhibitory potential against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study was a double-blind, randomized, placebo-controlled, multicenter, phase 2 clinical trial in mild to moderate COVID-19 patients. We randomly assigned patients to receive either camostat mesylate (DWJ1248) or placebo orally for 14 days. The primary endpoint was time to clinical improvement of subject symptoms within 14 days, measured using a subjective 4-point Likert scale. Three hundred forty-two patients were randomized. The primary endpoint was nonsignificant, where the median times to clinical improvement were 7 and 8 days in the camostat mesylate group and the placebo group, respectively (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 0.84 to 1.43; P = 0.50). A post hoc analysis showed that the difference was greatest at day 7, without reaching significance. In the high-risk group, the proportions of patients with clinical improvement up to 7 days were 45.8% (50/109) in the camostat group and 38.4% (40/104) in the placebo group (odds ratio [OR] = 1.33; 95% CI, 0.77 to 2.31; P = 0.31); the ordinal scale score at day 7 improved in 20.0% (18/90) of the camostat group and 13.3% (12/90) of the placebo group (OR = 1.68; 95% CI, 0.75 to 3.78; P = 0.21). Adverse events were similar in the two groups. Camostat mesylate was safe in the treatment of COVID-19. Although this study did not show clinical benefit in patients with mild to moderate COVID-19, further clinical studies for high-risk patients are needed. (This trial was registered with ClinicalTrials.gov under registration no. NCT04521296).

Effects of Subnormothermic Regulated Hepatic Reperfusion on Mitochondrial and Transcriptomic Profiles in a Porcine Model.

OBJECTIVE: We sought to investigate the biological effects of pre-reperfusion treatments of the liver after warm and cold ischemic injuries in a porcine donation after circulatory death model. SUMMARY OF BACKGROUND DATA: Donation after circulatory death represents a severe form of liver ischemia and reperfusion injury that has a profound impact on graft function after liver transplantation. METHODS: Twenty donor pig livers underwent 60 minutes of in situ warm ischemia after circulatory arrest and 120 minutes of cold static preservation prior to simulated transplantation using an ex vivo perfusion machine. Four reperfusion treatments were compared: Control-Normothermic (N), Control- Subnormothermic (S), regulated hepatic reperfusion (RHR)-N, and RHR-S (n = 5 each). The biochemical, metabolic, and transcriptomic profiles, as well as mitochondrial function were analyzed. RESULTS: Compared to the other groups, RHR-S treated group showed significantly lower post-reperfusion aspartate aminotransferase levels in the reperfusion effluent and histologic findings of hepatocyte viability and lesser degree of congestion and necrosis. RHR-S resulted in a significantly higher mitochondrial respiratory control index and calcium retention capacity. Transcriptomic profile analysis showed that treatment with RHR-S activated cell survival and viability, cellular homeostasis as well as other biological functions involved in tissue repair such as cytoskeleton or cytoplasm organization, cell migration, transcription, and microtubule dynamics. Furthermore, RHR-S inhibited organismal death, morbidity and mortality, necrosis, and apoptosis. CONCLUSION: Subnormothermic RHR mitigates IRI and preserves hepatic mitochondrial function after warm and cold hepatic ischemia. This organ resuscitative therapy may also trigger the activation of protective genes against IRI. Sub- normothermic RHR has potential applicability to clinical liver transplantation.

Impact of COVID-19 on abdominal organ transplantation: A bibliometric analysis.

BACKGROUND: Abdominal solid organ transplant (SOT) programs have been hit hard by the COVID-19 pandemic, which was officially declared as such on March 11, 2020. Over two years, the tightening and softening of limitations in response to the "waves" of infection and COVID-19 fluctuations have provided distinct issues for waitlisted patients, transplant recipients, and transplant organizations. METHOD: We searched Scopus using the terms "transplant" and "transplantation," and organ-related phrases like "intestin*," "liver," "kidney," "hepatic," "renal," and "pancrea*," as well as COVID-19 terms such as "COVID-19," "coronavirus," and "SARS-CoV-2." We included articles, reviews, conference papers, letters, notes, editorials, brief surveys, book chapters, and errata and studied nations, institutions, authors, journals, keywords, and articles. VOSviewer 1.6.18 and Excel were used to create tables and figures. RESULTS: We included 1,251 of 1,256 studies. Among them, 289 (23.1%), 489 (39.1%), and 473 (37.8%) papers were published in 2020, 2021, and 2022, with mean (SD) citations of 30.3 (53.3), 14.3 (26.8), and 4.79 (6.38), respectively. Compared to other abdominal organs, the field of kidney transplants had the highest number of articles describing the impact of COVID-19. The United States contributed the most articles, and the American Journal of Transplantation published the most articles. CONCLUSION: To our knowledge, this is the first bibliometric investigation of the impact of COVID-19 on SOT. This report provides an overview of the research conducted on SOT and COVID-19. There is potential for this bibliometric analysis to serve as a beneficial and practical resource for ongoing and future research.

The Impact of SRT2104 on Skeletal Muscle Mitochondrial Function, Redox Biology, and Loss of Muscle Mass in Hindlimb Unloaded Rats.

Mechanical unloading during microgravity causes skeletal muscle atrophy and impairs mitochondrial energetics. The elevated production of reactive oxygen species (ROS) by mitochondria and Nox2, coupled with impairment of stress protection (e.g., SIRT1, antioxidant enzymes), contribute to atrophy. We tested the hypothesis that the SIRT1 activator, SRT2104 would rescue unloading-induced mitochondrial dysfunction. Mitochondrial function in rat gastrocnemius and soleus muscles were evaluated under three conditions (10 days): ambulatory control (CON), hindlimb unloaded (HU), and hindlimb-unloaded-treated with SRT2104 (SIRT). Oxidative phosphorylation, electron transfer capacities, H2O2 production, and oxidative and antioxidant enzymes were quantified using high-resolution respirometry and colorimetry. In the gastrocnemius, (1) integrative (per mg tissue) proton LEAK was lesser in SIRT than in HU or CON; (2) intrinsic (relative to citrate synthase) maximal noncoupled electron transfer capacity (ECI+II) was lesser, while complex I-supported oxidative phosphorylation to ECI+II was greater in HU than CON; (3) the contribution of LEAK to ECI+II was greatest, but cytochrome c oxidase activity was lowest in HU. In both muscles, H2O2 production and concentration was greatest in SIRT, as was gastrocnemius superoxide dismutase activity. In the soleus, H2O2 concentration was greater in HU compared to CON. These results indicate that SRT2104 preserves mitochondrial function in unloaded skeletal muscle, suggesting its potential to support healthy muscle cells in microgravity by promoting necessary energy production in mitochondria.

Fluorescein clearance kinetics in blood and bile indicates hepatic ischemia-reperfusion injury in rats.

Quantitative measurement of the degree of hepatic ischemia-reperfusion injury (IRI) is crucial for developing therapeutic strategies for its treatment. We hypothesized that clearance of fluorescent dye through bile metabolism may reflect the degree of hepatic IRI. In this study, we investigated sodium fluorescein clearance kinetics in blood and bile for quantifying the degree of hepatic IRI. Warm ischemia times (WITs) of 0, 30, or 60 min followed by 1 h or 4 h of reperfusion, were applied to the median and lateral lobes of the liver in Sprague-Dawley rats. Subsequently, 2 mg/kg of sodium fluorescein was injected intravenously, and blood and bile samples were collected over 60 min to measure fluorescence intensities. The bile-to-plasma fluorescence ratios demonstrated an inverse correlation with WIT and were distinctly lower in the 60-min WIT group than in the control or 30-min WIT groups. Bile-to-plasma fluorescence ratios displayed superior discriminability for short versus long WITs when measured 1 h after reperfusion versus 4 h. We conclude that the bile-to-blood ratio of fluorescence after sodium fluorescein injection has the potential to enable the quantification of hepatic IRI severity.NEW & NOTEWORTHY Previous attempts to use fluorophore clearance to test liver function have relied on a single source of data. However, the kinetics of substrate processing via bile metabolism include decreasing levels in blood and increasing levels in bile. Thus, we analyzed data from blood and bile to better reflect fluorescein clearance kinetics.

The Efficacy of Orbital Septal Flap in the Treatment of Moderate and Severe Upper Eyelid Retraction.

PURPOSE: To assess the long-term effectiveness of the orbital septal flap to lengthen the levator muscle in management of moderate and severe upper eyelid retraction. METHODS: This study reports 46 eyes of 43 consecutive patients with moderate or severe upper eyelid retraction who were recommended for surgery. The period of the study was between October 2016 and October 2019. All cases were evaluated for eyelid position before and at 3, 6, and 12 months after the operation. Successful outcome was defined as "perfect," "acceptable," and "failure". RESULTS: The average age was 33.3 years (range, 16-59 years). The average orbital septal flap height was 5.28 ± 0.77 mm. Before surgery, 78.3% had 1 of 3 central upper eyelid retraction (group 1), and 21.7% had 1 of 3 lateral upper eyelid retraction (group 2). During follow-up postoperatively, all eyelid parameters of upper marginal reflex distance, upper scleral show, and palpebral fissure height significantly decreased compared with preoperative values in both groups. The result was considered "perfect" or "acceptable" in 42 eyes (91.3%). However, at 12 months after surgery, of the 36 middle eyelid retraction cases (group 1), 35 (97.2%) showed a successful outcome (perfect or acceptable results), while the success rate in group 2 was 70% (7 of 10 cases), a significant difference (p = 0.008). No severe complications were seen during follow up. CONCLUSIONS: Orbital septal flap is a safe and reliable procedure for management of upper eyelid retraction of moderate and severe degree.

Orbital Metastasis From Gastric Cancer Presenting as Orbital Cellulitis With Ptosis.

ABSTRACT: We report a rare case of orbital metastasis that originated from gastric carcinoma, which presented as orbital cellulitis with ptosis. Orbital metastasis accounts for about only 1% to 13% of orbital tumors. Orbital metastasis in orbital soft tissue or bony structures is very uncommon.A female patient with advanced gastric cancer with multiple metastases was referred to our clinic. She showed mild swelling and ptosis in her left eye. Contrast enhanced computed tomography imaging suggested orbital metastasis from gastric cancer in the superolateral aspect of the orbit. Based on her general condition and after consulting with an oncologist, we determined that fine needle biopsy and excisional biopsy for pathological diagnosis should not be performed as a therapeutic treatment.It is important to distinguish orbital metastasis from orbital cellulitis with ptosis especially for patients with family or personal history of cancer. Clinicians should collect a through medical history from patients and suggest contrast enhanced computed tomography for appropriate diagnosis. Assessing quality of life and aggressive treatment options is crucial for determining the best treatment for orbital metastasis.

Blowout Fracture Assessment Based on Computed Tomography and Endoscopy: The Effectiveness of Endoscopy for Fracture Repair.

ABSTRACT: The purpose of this study was to compare the configuration of blowout fracture observed through orbital computed tomography (CT) and endoscopy, then present the effectiveness of using an endoscope in reconstruction surgery of blowout fracture. We retrospectively reviewed the clinical records of 337 patients who underwent reconstruction surgery of blowout fracture between January 2017 and December 2020 in the Department of Ophthalmology at Korea University Guro Hospital. The patients were categorized into 3 groups based on preoperative CT findings as follows: combined orbital medial and floor wall fractures, trapdoor fractures, and large blowout fractures. The images obtained through CT and endoscopy were compared among the 3 groups. Endoscopy helped identify herniated soft tissue and posterior fracture margins, and it also provides better magnification and a brighter view of the posterior aspects of the fracture site. Furthermore, endoscopy can also provide educational opportunities to visualize the fracture site and help trainees understand the surgical procedure approach or orbital anatomy. Based on our results, we suggest using an endoscope during blowout fracture surgery as an effective approach to reduce postoperative complications due to endoscopy's advantages in clear visualization of the fracture site during operation.

Diffuse Large B-Cell Lymphoma Arising in the Lacrimal Sac.

ABSTRACT: The authors report a single case of diffuse large B-cell lymphoma arising in the lacrimal sac. Diffuse large B-cell lymphoma is a third most common primary ocular adnexal lymphoma, which is the most common primary ocular malignant disease in adults. A patient came to our clinic with epiphora and a growing mass in the lacrimal sac. Enhanced computed tomography imaging suggested the presence of a malignant tumor and surgical excision and biopsy were performed. A final diagnosis of diffuse large B-cell lymphoma was reached by immunohistological and immunochemical staining. Two months after surgery, diffuse large B-cell lymphoma relapse occurred in the lacrimal sac and the patient underwent 6 cycles of chemotherapy. Diffuse large B-cell lymphoma is a curable disease when diagnosed early, and aggressive biopsy during surgery of the lacrimal sac is necessary to diagnose diffuse large B-cell lymphoma in the early stage. It is important to distinguish diffuse large B-cell lymphoma from other lacrimal system diseases.

Changes in Direction of Eyelashes After Epiblepharon Surgery Using the Hotz Procedure.

PURPOSE: To analyze the change of direction of eyelashes after epiblepharon surgery using the Hotz procedure and to propose the appropriate correction amount to reduce the risk of undercorrection or overcorrection. METHODS: Surgical correction using the Hotz procedure was performed in 60 patients who then were followed for 3 months in Korea University Anam Hospital. Clinical photographs were collected before and after the correction to measure the angle of the lower eyelashes. RESULT: The average angle before and after correction was 38.5° and -24.1°, respectively. The lower eyelashes gradually became introverted, and the amount of angle change was 9.3° at postoperative 1 month ( P < 0.001). These lashes become slightly extroverted to -15.0° at 3 months after the correction. CONCLUSIONS: Lower eyelashes become introverted to about 9 degrees after surgical correction. They become more introverted after operation when the epiblepharon is more severe and when they are more reconditioned to extroversion immediately after the operation.

Comparison of Blowout Fracture Sites Observed in Young and Elderly East Asians.

ABSTRACT: The purpose of this study was to investigate the distribution of blowout fracture sites among age groups and compare clinical factors that can affect the fracture site. The authors reviewed 330 cases of blowout fracture surgeries and included 226 eyes of 226 patients aged between 20 and 29 years and between 50 and 59 years who underwent blowout fracture reconstruction between January 2017 and December 2020, in the Department of Ophthalmology at Korea University Hospital.Medical records including patient demography, trauma etiology, and preoperative computed tomography image were evaluated. Ethmoidal cell septa and fracture site position were compared between the 2 age groups. The causes of injury were categorized into 3 groups: focal trauma, gross trauma, and other causes. Orbital floor fracture was the most common type (40.00%) in the young group, followed by medial wall fracture (25.33%). in contrast, medial wall fracture accounted for the largest proportion (42.11%) in the older group, and orbital floor fracture accounted for only 26.67%. The major cause of blowout fracture in young patients was focal trauma, whereas gross trauma was the most common cause in the older group. The number of ethmoidal cells was 4.19 ±â€Š0.831 (2-6) in the young group and 3.91 ±â€Š1.022 (2-6) in the old group (P  < 0.05). Distribution of blowout fracture site differed between age groups, and these differences can be explained by cause of injury and number of ethmoidal cells.

Analysis of Patients With Blowout Fracture Caused by Baseball Trauma.

ABSTRACT: The purpose of this study was to investigate the characteristics of blowout fractures caused by baseball trauma. The authors reviewed 337 cases of blowout fracture surgeries and included 330 eyes of 330 patients who underwent blowout fracture reconstruction between January 2017 and December 2020, in the Department of Ophthalmology at Korea university Hospital.Medical records including patient demography, trauma etiology, accompanied ocular disease, and preoperative computed tomography images were evaluated. Patients were categorized into 2 groups: a group with blowout fracture caused by baseball trauma and another group with trauma due to other causes. Two-wall blowout fracture (orbital floor fracture and medial wall fracture) was most common (63.16%) in the baseball group, followed by medial wall fracture (21.05%). In contrast, orbital floor fracture accounted for the largest proportion (42.11%) among other causes, and 2-wall blowout fracture accounted for the second largest proportion (31.83%). The most common accompanied ocular disease was traumatic hyphema and traumatic iridocyclitis (36.84%) in the baseball blowout fracture group. in contrast, subconjunctival hemorrhage was the most common ocular disease in the other-causes group (16.08%). The frequency of traumatic hyphema and irido-cyclitis was significantly different among the 2 groups (P  < 0.05). Distribution of blowout fracture sites and frequent ocular disease differed between baseball blowout fracture patients and other-cause blowout fracture patients.

Changes in Lower Eyelid Positions After Blepharoplasty and Levator Advancement Surgery.

PURPOSE: To investigate changes in the upper and lower eyelid positions using information from before and immediately after surgery in patients who underwent upper blepharoplasty and ptosis surgery. MATERIALS AND METHODS: We retrospectively reviewed the clinical records of patients who underwent upper blepharoplasty with a diagnosis of dermatochalasis and patients who underwent levator advancement or levator resection with a diagnosis of congenital or aponeurotic ptosis. The marginal reflex distance 1 (MRD1), marginal reflex distance 2 (MRD2), palpebral fissure height (PFH), and operation time were also investigated. RESULT: In the dermatochalasis group, the preoperative mean MRD1, MRD2, and PFH were 1.94±1.27, 4.71±0.95, and 6.65±1.65 mm, respectively. Mean MRD1, MRD2, and PFH values immediately after surgery were 1.80±0.79, 4.22±0.90, and 6.02±1.34 mm, respectively. In the ptosis group, the preoperative mean MRD1, MRD2, and PFH values were 0.27±1.34, 5.73±1.13, and 5.99±1.94 mm, respectively. Postoperative mean MRD1, MRD2, and PFH were 1.76±1.13, 4.22±1.01, and 5.98±1.60 mm, respectively. CONCLUSIONS: It is important to remember that MRD2 could decrease during surgery. Therefore, to prevent overcorrection after upper eyelid surgery, MRD1 (not the overall PFH) should be considered to determine the appropriate extent of surgery during the procedure.

Intraoperative Significance of Lower Eyelid Positions in Levator Advancement to Prevent Overcorrection.

PURPOSE: The purpose of this study was to investigate changes in the position of the upper and lower eyelids before and immediately after surgery in patients that underwent ptosis surgery. METHODS: The authors retrospectively reviewed the clinical records of patients diagnosed with congenital or aponeurotic ptosis and that were treated with levator advancement with local anesthesia. The marginal reflex distance 1 (MRD1), marginal reflex distance 2 (MRD2), and palpebral fissure height (PFH) were measured using clinical photographs. RESULT: The preoperative mean MRD1, MRD2, and PFH were 0.27 ± 1.34 mm, 5.73 ± 1.13 mm, and 5.99 ± 1.94 mm, respectively. The postoperative mean MRD1, MRD2, and PFH were 1.76 ± 1.03 mm, 4.22 ± 1.01 mm, and 5.98 ± 1.60 mm, respectively. The postoperative MRD1 was significantly increased and postoperative MRD2 was decreased significantly compared to preoperative values (both, P < 0.001). The preoperative and postoperative PFH values were not significantly different ( P = 0.941). CONCLUSIONS: It is important to assess the degree of reverse ptosis before surgery in patients that undergo ptosis surgery, and to remember that MRD2 and PFH may be reduced during surgery. Therefore, the position of the upper eyelid should be intraoperatively adjusted based on MRD1, not the PFH, to prevent overcorrection after surgery.

Clinical Manifestations in Patients Wearing Ocular Prostheses.

PURPOSE: This study aimed to assess upper and lower eyelid shapes and changes in patients wearing ocular prostheses. METHODS: The authors retrospectively reviewed the clinical records of patients wearing ocular prostheses. Clinical manifestations, including superior sulcus deepening, ptosis, upper and lower eyelid entropion, upper and lower eyelid ectropion, upper and lower eyelid retraction, and upper and lower eyelid socket contracture were investigated. RESULTS: For those patients who underwent evisceration, the most common clinical manifestations of the eyelid were superior sulcus deepening and ptosis (35%, respectively), whereas lower eyelid entropion and lower eyelid retraction were the second most common manifestations (25%, respectively). Among those patients who underwent enucleation, the most common eyelid changes were lower eyelid entropion (45.5%), and ptosis and lower eyelid socket contracture were the second most common alterations (36.4%, respectively). Finally, superior sulcus deepening, upper eyelid entropion, and lower eyelid retraction occurred in 27.3% of patients, respectively. CONCLUSIONS: Upper eyelid ptosis, superior sulcus deepening, and lower eyelid entropion and retraction were the most common clinical manifestations in patients wearing ocular prostheses. When following up with patients with ocular prostheses, it is important to check these eyelid changes and consider making appropriate corrections.

Fabrication of Ag-doped ZnO/PAN composite nanofibers by electrospinning: Photocatalytic and antiviral activities.

Ag-doped ZnO nanoparticles (AZNs) were directly synthesized using sol-gel method to embed into polyacrylonitrile (PAN) nanofibers by electrospinning. The synthesized AZNs were optically and structurally characterized by UV-VIS spectroscopy, photoluminescence spectroscopy, high resolution HR-TEM and XRD. The photocatalytic activity of the AZNs was examined by photocatalytic degradation of methylene blue to correlate with their antiviral efficacy in PAN nanofibers fabricated via electrospinning technique. The PAN nanofibers containing AZNs were characterized using SEM and EDS. Finally, antiviral activity of AZNs/PAN nanofibers was investigated by using virus ϕx174 under visible light irradiation. As a result, the antiviral efficacy of nanofibers increased as the concentration of Ag in AZNs increased. The results show that better antiviral efficacy was obtained in AZNs/PAN nanofibers prepared with AZNs of higher photocatalytic performance.

Liver Transplantation Outcomes in a U.S. Multicenter Cohort of 789 Patients With Hepatocellular Carcinoma Presenting Beyond Milan Criteria.

BACKGROUND AND AIMS: The Organ Procurement and Transplantation Network recently approved liver transplant (LT) prioritization for patients with hepatocellular carcinoma (HCC) beyond Milan Criteria (MC) who are down-staged (DS) with locoregional therapy (LRT). We evaluated post-LT outcomes, predictors of down-staging, and the impact of LRT in patients with beyond-MC HCC from the U.S. Multicenter HCC Transplant Consortium (20 centers, 2002-2013). APPROACH AND RESULTS: Clinicopathologic characteristics, overall survival (OS), recurrence-free survival (RFS), and HCC recurrence (HCC-R) were compared between patients within MC (n = 3,570) and beyond MC (n = 789) who were down-staged (DS, n = 465), treated with LRT and not down-staged (LRT-NoDS, n = 242), or untreated (NoLRT-NoDS, n = 82). Five-year post-LT OS and RFS was higher in MC (71.3% and 68.2%) compared with DS (64.3% and 59.5%) and was lowest in NoDS (n = 324; 60.2% and 53.8%; overall P < 0.001). DS patients had superior RFS (60% vs. 54%, P = 0.043) and lower 5-year HCC-R (18% vs. 32%, P < 0.001) compared with NoDS, with further stratification by maximum radiologic tumor diameter (5-year HCC-R of 15.5% in DS/<5 cm and 39.1% in NoDS/>5 cm, P < 0.001). Multivariate predictors of down-staging included alpha-fetoprotein response to LRT, pathologic tumor number and size, and wait time >12 months. LRT-NoDS had greater HCC-R compared with NoLRT-NoDS (34.1% vs. 26.1%, P < 0.001), even after controlling for clinicopathologic variables (hazard ratio [HR] = 2.33, P < 0.001) and inverse probability of treatment-weighted propensity matching (HR = 1.82, P < 0.001). CONCLUSIONS: In LT recipients with HCC presenting beyond MC, successful down-staging is predicted by wait time, alpha-fetoprotein response to LRT, and tumor burden and results in excellent post-LT outcomes, justifying expansion of LT criteria. In LRT-NoDS patients, higher HCC-R compared with NoLRT-NoDS cannot be explained by clinicopathologic differences, suggesting a potentially aggravating role of LRT in patients with poor tumor biology that warrants further investigation.