Incidence and Mortality of Emergency General Surgery Conditions Among Solid Organ Transplant Recipients in Ontario, Canada: A Population-based Analysis.

BACKGROUND: Emergency general surgery (EGS) conditions and their outcomes are perceived to be disproportionately high among solid organ transplant recipients (SOTRs). However, this has not been adequately investigated at a population level. We characterized the incidence and mortality of EGS conditions among SOTRs compared with nontransplant patients. METHODS: Data were collected through linked administrative population-based databases in Ontario, Canada. We included all adult SOTRs (kidney, liver, heart, and lung) who underwent transplantation between 2002 and 2017. We then identified posttransplantation emergency department visits for EGS conditions (appendicitis, cholecystitis, choledocolithiasis, perforated diverticulitis, incarcerated/strangulated hernias, small bowel obstruction, and perforated peptic ulcer). Age-, sex-, and year-standardized incidence rate ratios (SIRRs) were generated. Logistic regression models were used to evaluate association between transplantation status and 30 d mortality after adjusting for demographics, year, and comorbidities. RESULTS: Ten thousand seventy-three SOTRs and 12 608 135 persons were analyzed. SOTRs developed 881 EGS conditions (non-SOTRs: 552 194 events). The incidence of all EGS conditions among SOTR was significantly higher compared with the nontransplant patients [SIRR 3.56 (95% confidence interval [CI] 3.32-3.82)], even among those with high Aggregated Diagnosis Groups scores ( > 10) [SIRR 2.76 (95% CI 2.53-3.00)]. SOTRs were 1.4 times more likely to die at 30 d [adjusted odds ratio 1.44 (95% CI 1.08-1.91)] after an EGS event compared with nontransplant patients, predominantly amongst lung transplant recipients [adjusted odds ratio 3.28 (95% CI 1.72-6.24)]. CONCLUSIONS: The incidence of EGS conditions is significantly higher in SOTRs even after stratifying by comorbidity burden. This is of particular importance as SOTRs also have a higher likelihood of death after an EGS condition, especially lung transplant recipients.

Hybrid and vaccine-induced immunity against SARS-CoV-2 in MS patients on different disease-modifying therapies

ObjectiveTo compare hybrid immunity (prior COVID-19 infection plus vaccination) and post-vaccination immunity to SARS CoV-2 in MS patients on different disease-modifying therapies (DMTs) and to assess the impact of vaccine product and race/ethnicity on post-vaccination immune responses. MethodsConsecutive MS patients from NYU MS Care Center (New York, NY), aged 18-60, who completed COVID-19 vaccination series [≥]6 weeks previously were evaluated for SARS CoV-2-specific antibody responses with electro-chemiluminescence and multiepitope bead-based immunoassays and, in a subset, live virus immunofluorescence-based microneutralization assay. SARS CoV-2-specific cellular responses were assessed with cellular stimulation TruCulture IFN{gamma} and IL-2 assay and, in a subset, with IFN{gamma} and IL-2 ELISpot assays. Multivariate analyses examined associations between immunologic responses and prior COVID-19 infection while controlling for age, sex, DMT at vaccination, time-to-vaccine, and vaccine product. ResultsBetween 6/01/2021-11/11/2021, 370 MS patients were recruited (mean age 40.6 years; 76% female; 53% non-White; 22% with prior infection; common DMT classes: ocrelizumab 40%; natalizumab 15%, sphingosine-1-phosphate receptor modulators 13%; and no DMT 8%). Vaccine-to-collection time was 18.7 ({+/-}7.7) weeks and 95% of patients received mRNA vaccines. In multivariate analyses, patients with laboratory-confirmed prior COVID-19 infection had significantly increased antibody and cellular post-vaccination responses compared to those without prior infection. Vaccine product and DMT class were independent predictors of antibody and cellular responses, while race/ethnicity was not. InterpretationPrior COVID-19 infection is associated with enhanced antibody and cellular post-vaccine responses independent of DMT class and vaccine type. There were no differences in immune responses across race/ethnic groups.

Prime-boost vaccination regimens with INO-4800 and INO-4802 augment and broaden immune responses against SARS-CoV-2 in nonhuman primates.

The enhanced transmissibility and immune evasion associated with emerging SARS-CoV-2 variants demands the development of next-generation vaccines capable of inducing superior protection amid a shifting pandemic landscape. Since a portion of the global population harbors some level of immunity from vaccines based on the original Wuhan-Hu-1 SARS-CoV-2 sequence or natural infection, an important question going forward is whether this immunity can be boosted by next-generation vaccines that target emerging variants while simultaneously maintaining long-term protection against existing strains. Here, we evaluated the immunogenicity of INO-4800, our synthetic DNA vaccine candidate for COVID-19 currently in clinical evaluation, and INO-4802, a next-generation DNA vaccine designed to broadly target emerging SARS-CoV-2 variants, as booster vaccines in nonhuman primates. Rhesus macaques primed over one year prior with the first-generation INO-4800 vaccine were boosted with either INO-4800 or INO-4802 in homologous or heterologous prime-boost regimens. Both boosting schedules led to an expansion of T cells and antibody responses which were characterized by improved neutralizing and ACE2 blocking activity across wild-type SARS-CoV-2 as well as multiple variants of concern. These data illustrate the durability of immunity following vaccination with INO-4800 and additionally support the use of either INO-4800 or INO-4802 in prime-boost regimens.

Cellular and humoral immunity to SARS-CoV-2 infection in multiple sclerosis patients on ocrelizumab and other disease-modifying therapies: a multi-ethnic observational study

ObjectiveTo determine the impact of MS disease-modifying therapies (DMTs) on the development of cellular and humoral immunity to SARS-CoV-2 infection. MethodsMS patients aged 18-60 were evaluated for anti-nucleocapsid and anti-Spike RBD antibody with electro-chemiluminescence immunoassay; antibody responses to Spike protein, RBD, N-terminal domain with multiepitope bead-based immunoassays (MBI); live virus immunofluorescence-based microneutralization assay; T-cell responses to SARS-CoV-2 Spike using TruCulture ELISA; and IL-2 and IFN{gamma} ELISpot assays. Assay results were compared by DMT class. Spearman correlation and multivariate analyses were performed to examine associations between immunologic responses and infection severity. ResultsBetween 1/6/2021 and 7/21/2021, 389 MS patients were recruited (mean age 40.3 years; 74% female; 62% non-White). Most common DMTs were ocrelizumab (OCR) - 40%; natalizumab - 17%, Sphingosine 1-phosphate receptor (S1P) modulators -12%; and 15% untreated. 177 patients (46%) had laboratory evidence of SARS-CoV-2 infection; 130 had symptomatic infection, 47 - asymptomatic. Antibody responses were markedly attenuated in OCR compared to other groups (p[≤] 0001). T-cell responses (IFN{gamma} were decreased in S1P (p=0.03), increased in natalizumab (p<0.001), and similar in other DMTs, including OCR. Cellular and humoral responses were moderately correlated in both OCR (r=0.45, p=0.0002) and non-OCR (r=0.64, p<0.0001). Immune responses did not differ by race/ethnicity. COVID-19 clinical course was mostly non-severe and similar across DMTs; 7% (9/130) were hospitalized. InterpretationDMTs had differential effects on humoral and cellular immune responses to SARS-CoV-2 infection. Immune responses did not correlate with COVID-19 clinical severity in this relatively young and non-disabled group of MS patients.

Generation of Astrocyte-Specific MAOB Conditional Knockout Mouse with Minimal Tonic GABA Inhibition

Monoamine oxidase B (MAOB) is a key enzyme for GABA production in astrocytes in several brain regions. To date, the role of astrocytic MAOB has been studied in MAOB null knockout (KO) mice, although MAOB is expressed throughout the body. Therefore, there has been a need for genetically engineered mice in which only astrocytic MAOB is targeted. Here, we generated an astrocyte-specific MAOB conditional KO (cKO) mouse line and characterized it in the cerebellar and striatal regions of the brain. Using the CRISPR-Cas9 gene-editing technique, we generated Maob floxed mice (B6-Maob em1Cjl /Ibs) which have floxed exons 2 and 3 of Maob with two loxP sites. By crossing these mice with hGFAP-CreER T2 , we obtained Maob floxed::hGFAP-CreER T2 mice which have a property of tamoxifen-inducible ablation of Maob under the human GFAP (hGFAP) promoter. When we treated Maob floxed::hGFAP-CreER T2 mice with tamoxifen for 5 consecutive days, MAOB and GABA immunoreactivity were significantly reduced in striatal astrocytes as well as in Bergmann glia and lamellar astrocytes in the cerebellum, compared to sunflower oil-injected control mice. Moreover, astrocyte-specific MAOB cKO led to a 74.6% reduction in tonic GABA currents from granule cells and a 76.8% reduction from medium spiny neurons. Our results validate that astrocytic MAOB is a critical enzyme for the synthesis of GABA in astrocytes. We propose that this new mouse line could be widely used in studies of various brain diseases to elucidate the pathological role of astrocytic MAOB in the future.

Unaltered Tonic Inhibition in the Arcuate Nucleus of Diet-induced Obese Mice

The principal inhibitory transmitter, γ-aminobutyric acid (GABA), is critical for maintaining hypothalamic homeostasis and released from neurons phasically, as well as from astrocytes tonically. Although astrocytes in the arcuate nucleus (ARC) of the hypothalamus are shown to transform into reactive astrocytes, the tonic inhibition by astrocytic GABA has not been adequately investigated in diet-induced obesity (DIO). Here, we investigated the expression of monoamine oxidase- B (MAOB), a GABA-synthesizing enzyme, in reactive astrocytes in obese mice. We observed that a chronic high-fat diet (HFD) significantly increased astrocytic MAOB and cellular GABA content, along with enhanced hypertrophy of astrocytes in the ARC. Unexpectedly, we found that the level of tonic GABA was unaltered in chronic HFD mice using whole-cell patch-clamp recordings in the ARC. Furthermore, the GABA-induced current was increased with elevated GABA A receptor α5 (GABRA5) expression. Surprisingly, we found that a nonselective GABA transporter (GAT) inhibitor, nipecotic acid (NPA)-induced current was significantly increased in chronic HFD mice. We observed that GAT1 inhibitor, NO711-induced current was significantly increased, whereas GAT3 inhibitor, SNAP5114-induced current was not altered. The unexpected unaltered tonic inhibition was due to an increase of GABA clearance in the ARC by neuronal GAT1 rather than astrocytic GAT3. These results imply that increased astrocytic GABA synthesis and neuronal GABA A receptor were compensated by GABA clearance, resulting in unaltered tonic GABA inhibition in the ARC of the hypothalamus in obese mice. Taken together, GABA-related molecular pathways in the ARC dynamically regulate the tonic inhibition to maintain hypothalamic homeostasis against the HFD challenge.

Time-Varying Proteinuria and the Risk of Cardiovascular Disease and Graft Failure in Kidney Transplant Recipients.

Introduction: Proteinuria is recognized as an independent risk factor for cardiovascular disease in kidney transplant recipients, but previous studies have not considered the impact of changes in urine protein over time. Research Question and Design: We used time-dependent, multivariable Cox proportional hazards models in this observational cohort study of adult kidney transplant recipients to evaluate whether proteinuria measured by dipstick on random spot urine samples starting from 1-month post-transplant was associated with the risk of major adverse cardiac events and graft loss. Results: A total of 144 major adverse cardiac events, defined as acute myocardial infarction, cerebrovascular accident, revascularization, or all-cause mortality, were observed in 1106 patients over 5728.7 person-years. Any level of proteinuria greater or equal to trace resulted in a two-fold increase in the risk of major adverse cardiac events (hazard ratio 2.00 [95% confidence interval 1.41, 2.84]). This relationship was not found to be dose-dependent (hazard ratios of 2.98, 1.76, 1.63, and 1.54 for trace, 1+, 2+, and 3+ urine protein, respectively). There was an increased risk of graft failure with greater urine protein concentration (hazard ratios 2.22, 2.85, 6.41, and 19.71 for trace, 1+, 2+, and 3+, respectively). Conclusion: Urine protein is associated with major adverse cardiac events and graft loss in kidney transplant recipients. The role of interventions to reduce proteinuria on decreasing the risk of adverse cardiovascular and graft outcomes in kidney transplant recipients requires further study.

INO-4800 DNA vaccine induces neutralizing antibodies and T cell activity against global SARS-CoV-2 variants.

Global surveillance has identified emerging SARS-CoV-2 variants of concern (VOC) associated with broadened host specificity, pathogenicity, and immune evasion to vaccine-induced immunity. Here we compared humoral and cellular responses against SARS-CoV-2 VOC in subjects immunized with the DNA vaccine, INO-4800. INO-4800 vaccination induced neutralizing antibodies against all variants tested, with reduced levels detected against B.1.351. IFNγ T cell responses were fully maintained against all variants tested.

Prime-boost vaccination regimens with INO-4800 and INO-4802 augment and broaden immune responses against SARS-CoV-2 in nonhuman primates

The enhanced transmissibility and immune evasion associated with emerging SARS-CoV-2 variants demands the development of next-generation vaccines capable of inducing superior protection amid a shifting pandemic landscape. Since a portion of the global population harbors some level of immunity from vaccines based on the original Wuhan-Hu-1 SARS-CoV-2 sequence or natural infection, an important question going forward is whether this immunity can be boosted by next-generation vaccines that target emerging variants while simultaneously maintaining long-term protection against existing strains. Here, we evaluated the immunogenicity of INO-4800, our synthetic DNA vaccine candidate for COVID-19 currently in clinical evaluation, and INO-4802, a next-generation DNA vaccine designed to broadly target emerging SARS-CoV-2 variants, as booster vaccines in nonhuman primates. Rhesus macaques primed over one year prior with the first-generation INO-4800 vaccine were boosted with either INO-4800 or INO-4802 in homologous or heterologous prime-boost regimens. Both boosting schedules led to an expansion of antibody responses which were characterized by improved neutralizing and ACE2 blocking activity across wild-type SARS-CoV-2 as well as multiple variants of concern. These data illustrate the durability of immunity following vaccination with INO-4800 and additionally support the use of either INO-4800 or INO-4802 in prime-boost regimens.

SARS-CoV-2 DNA Vaccine INO-4800 Induces Durable Immune Responses Capable of Being Boosted in a Phase 1 Open-Label Trial

BackgroundAdditional SARS-CoV-2 vaccines that are safe and effective as primary vaccines and boosters remain urgently needed to combat the COVID-19 pandemic. We describe the safety and durability of the immune responses following two primary doses and a homologous booster dose of an investigational DNA vaccine (INO-4800) targeting the full-length spike antigen. MethodsThree dosage strengths of INO-4800 (0.5 mg, 1.0 mg, and 2.0 mg) were evaluated in 120 age-stratified healthy adults. Intradermal injection of INO-4800 followed by electroporation at 0 and 4 weeks preceded an optional booster 6-10.5 months after the second dose. ResultsINO-4800 appeared well tolerated, with no treatment-related serious adverse events. Most adverse events were mild and did not increase in frequency with age and subsequent dosing. A durable antibody response was observed 6 months following the second dose; a homologous booster dose significantly increased immune responses. Cytokine producing T cells and activated CD8+ T cells with lytic potential were significantly increased in the 2.0 mg dose group. ConclusionINO-4800 was well tolerated in a 2-dose primary series and as a homologous booster in all adults, including the elderly. These results support further development of INO-4800 for use as a primary vaccine and as a booster. Trial Registration: ClinicalTrials.gov NCT04336410 SummaryTwo-milligram dose of INO-4800, a DNA-based vaccine encoding the SARS-CoV-2 spike protein, appears safe and well-tolerated and elicits humoral and cell-mediated immunity persisting to 6 months after a second dose. A third dose 6-10.5 months later significantly boosts immune responses.

Design and immunogenicity of a Pan-SARS-CoV-2 synthetic DNA vaccine

Here we have employed SynCon(R) design technology to construct a DNA vaccine expressing a pan-Spike immunogen (INO-4802) to induce broad immunity across SARS-CoV-2 variants of concern (VOC). Compared to WT and VOC-matched vaccines which showed reduced cross-neutralizing activity, INO-4802 induced potent neutralizing antibodies and T cell responses against WT as well as B.1.1.7, P.1, and B.1.351 VOCs in a murine model. In addition, a hamster challenge model demonstrated that INO-4802 conferred superior protection following intranasal B.1.351 challenge. Protection against weight loss associated with WT, B.1.1.7, P.1 and B.1.617.2 challenge was also demonstrated. Vaccinated hamsters showed enhanced humoral responses against VOC in a heterologous WT vaccine prime and INO-4802 boost setting. These results demonstrate the potential of the pan-SARS-CoV-2 vaccine, INO-4802 to induce cross-reactive immune responses against emerging VOC as either a standalone vaccine, or as a potential boost for individuals previously immunized with WT-matched vaccines.

Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2: a preliminary report of a randomized, blinded, placebo-controlled, Phase 2 clinical trial in adults at high risk of viral exposure

BackgroundVaccines against SARS-CoV-2 are still urgently needed as only 5% of the global population has been vaccinated. Here we report the safety and immunogenicity of a DNA vaccine (INO-4800) targeting the full-length Spike antigen of SARS-CoV-2 when given to adults at high-risk of exposure. MethodsINO-4800 was evaluated in 401 participants randomized at a 3:3:1:1 ratio to receive either INO-4800 (1 mg or 2 mg dose) or placebo (1 or 2 injections) intradermally (ID) followed by electroporation (EP) using CELLECTRA(R) 2000 at Days 0 and 28. ClinicalTrials.gov Identifier: NCT04642638 FindingsThe majority of adverse events (AEs) were of Grade 1 and 2 in severity and did not appear to increase in frequency with the second dose. The number of participants experiencing each of the most common AEs did not differ appreciably between the two dosing groups. The geometric mean fold rise (GMFR) of binding and neutralizing antibody levels were statistically significantly greater in the 2.0 mg dose group versus the 1.0 mg dose group. The T cell immune responses measured by the ELISpot assay were also higher in the 2.0 mg dose group compared to the 1.0 mg dose group. InterpretationINO-4800 at both the 1.0 mg and 2.0 mg doses when administered in a 2-dose regimen appeared to be safe and well-tolerated in all adult ages. However, the comparative immunogenicity analysis favored selection of INO-4800 2.0 mg dose for advancement into a Phase 3 efficacy evaluation. FundingThe trial was funded by the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense, (JPEO-CBRND) in coordination with the Office of the Assistant Secretary of Defense for Health Affairs (OASD(HA)) and the Defense Health Agency. Research in contextINO-4800 is among several vaccines being tested against SARS-CoV-2, the virus that causes COVID-19 with the goal of inducing a protective immune response. The DNA vaccine, INO-4800, administered by ID injection followed by electroporation (EP) using the CELLECTRA(R) 2000 device, induces a balanced immune response that includes engagement of both T cells and B 1-5. Added value of this studyThis is the first report of a randomized, blinded, placebo-controlled clinical trial of INO-4800, a DNA vaccine targeting the SARS-CoV-2 Spike antigen delivered ID followed by EP, in adults at high risk of SARS-CoV-2 exposure.

INO-4800 DNA Vaccine Induces Neutralizing Antibodies and T cell Activity Against Global SARS-CoV-2 Variants

Global surveillance has identified emerging SARS-CoV-2 variants of concern (VOC) associated with broadened host specificity, pathogenicity, and immune evasion to vaccine induced immunity. Here we compared humoral and cellular responses against SARS-CoV-2 VOC in subjects immunized with the DNA vaccine, INO-4800. INO-4800 vaccination induced neutralizing antibodies against all variants tested, with reduced levels detected against B.1.351. IFN{gamma} T cell responses were fully maintained against all variants tested.

Early postoperative acute myocardial infarction in kidney transplant recipients: A nested case-control study.

INTRODUCTION: The epidemiology of early acute myocardial infarctions after kidney transplantation has not been well characterized. This study sought to examine the incidence, risk factors, and clinical outcomes of early acute myocardial infarctions or EAMI in kidney transplant recipients. METHODS: A total of 1976 patients who underwent kidney transplantation at our center from Jan 1, 2000, to Sept 30, 2016, were included. A nested case-control design was used to study EAMI risk factors using a conditional logistic regression model. A Cox proportional hazards model was used to assess the association of EAMI with death-censored graft failure, death with graft function, and total graft failure. RESULTS: Seventy four patients had an EAMI within 3 months post-transplant. Based on univariable analyses, risk factors for EAMI included age and recipient history of diabetes mellitus or coronary artery disease. After adjustment, recipient history of coronary artery disease was the only independent predictor for EAMI (OR 3.76, p < .001). Patients who experienced EAMI were more likely to experience death-censored graft failure, death with graft function, and total graft failure. CONCLUSION: While the incidence of EAMI in kidney transplant recipients is relatively low, these data show that EAMI has profound long-term effects on morbidity and mortality.

Prediction of the Expected Extent of Surgical Difficulty When Removing an Idiopathic Epiretinal Membrane

Purpose@#We sought to predict how difficult surgical removal of an epiretinal membrane (ERM) might be by analyzing the preoperative characteristics of the ERM. @*Methods@#From 2016 to 2020, 75 patients diagnosed with idiopathic ERMs who underwent ERM removal were evaluated in terms of surgical time (via video analysis); associations between that time and preoperative color fundus photographs and optical coherence tomography findings were sought. @*Results@#The surgical time was associated with the vascular tortuosity grade, the ERM stage, and fibrillary changes (p = 0.024, p = 0.020, and p = 0.018). Dummy regression analysis showed that EMR stage 4, and vascular tortuosity grades of 2 or 3, increased the surgical time (p = 0.036, p = 0.049). @*Conclusions@#Surgery may be difficult if the ERM is of stage 4 or the vascular tortuosity grade 2 or more. A retinal surgery novice should consider these factors when contemplating surgery.

Prediction of the Expected Extent of Surgical Difficulty When Removing an Idiopathic Epiretinal Membrane

Purpose@#We sought to predict how difficult surgical removal of an epiretinal membrane (ERM) might be by analyzing the preoperative characteristics of the ERM. @*Methods@#From 2016 to 2020, 75 patients diagnosed with idiopathic ERMs who underwent ERM removal were evaluated in terms of surgical time (via video analysis); associations between that time and preoperative color fundus photographs and optical coherence tomography findings were sought. @*Results@#The surgical time was associated with the vascular tortuosity grade, the ERM stage, and fibrillary changes (p = 0.024, p = 0.020, and p = 0.018). Dummy regression analysis showed that EMR stage 4, and vascular tortuosity grades of 2 or 3, increased the surgical time (p = 0.036, p = 0.049). @*Conclusions@#Surgery may be difficult if the ERM is of stage 4 or the vascular tortuosity grade 2 or more. A retinal surgery novice should consider these factors when contemplating surgery.

Intradermal-delivered DNA vaccine provides anamnestic protection in a rhesus macaque SARS-CoV-2 challenge model

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has had a dramatic global impact on public health, social, and economic infrastructures. Here, we assess immunogenicity and anamnestic protective efficacy in rhesus macaques of the intradermal (ID)-delivered SARS-CoV-2 spike DNA vaccine, INO-4800. INO-4800 is an ID-delivered DNA vaccine currently being evaluated in clinical trials. Vaccination with INO-4800 induced T cell responses and neutralizing antibody responses against both the D614 and G614 SARS-CoV-2 spike proteins. Several months after vaccination, animals were challenged with SARS-CoV-2 resulting in rapid recall of anti-SARS-CoV-2 spike protein T and B cell responses. These responses were associated with lower viral loads in the lung and with faster nasal clearance of virus. These studies support the immune impact of INO-4800 for inducing both humoral and cellular arms of the adaptive immune system which are likely important for providing durable protection against COVID-19 disease.

Elevated Risk of Cancer After Solid Organ Transplant in Childhood: A Population-based Cohort Study.

BACKGROUND: Cancer risk is elevated among adult transplant recipients, but there is limited data regarding long-term cancer risk and mortality in pediatric recipients. METHODS: We conducted a population-based retrospective cohort study in Ontario, Canada. We included pediatric recipients of solid organ transplants at the Hospital for Sick Children, Toronto, from 1991 to 2014, and compared rates of new cancers and cancer-specific mortality to nontransplanted Ontario children born in the same year. We constructed standard and time-dependent Cox proportional hazards models accounting for competing risk of death. RESULTS: A total of 951 recipients (kidney, n = 400; liver, n = 283; heart, n = 218; lung, n = 36; multiorgan/small bowel, n = 14) were compared with 5.3 million general population children. Mean (SD) age was 8.2 (6.4) years; 50% were male. Over a mean (SD) follow-up of 10.8 (7.1) years, cumulative incidence of cancer was 20% in recipients and 1.2% in the general population (incidence rate ratio, 32.9; 95% confidence interval [CI], 26.6-40.8). Risk was highest in the first year posttransplant (adjusted hazard ratio [aHR],176; 95% CI, 117-264), but remained elevated beyond 10 years (aHR, 10.8; 95% CI, 6.3-18.6). Lymphoproliferative disorders were predominant (77%); however, solid cancers (renal, sarcomas, genital, thyroid) were seen. Recipients of lung or multiorgan transplants were at highest risk. Cancer-specific mortality was also higher among recipients (HR, 93.1; 95% CI, 59.6-145.2). CONCLUSIONS: Childhood transplant recipients have a 30 times greater cancer incidence versus the general population. Further investigation is needed to guide screening strategies in this at-risk population.

Atypical Fundus Manifestation of Ocular Toxocariasis

No abstract available.

Factors Affecting Persistent Diplopia after Surgical Repair of Isolated Inferior Orbital Wall Fracture

PURPOSE: To investigate factors affecting persistent diplopia after surgical repair of isolated inferior orbital wall fractures. METHODS: Thirty-three patients who underwent surgical repair of isolated inferior orbital wall fractures in Inha University Hospital Ophthalmology Department from 2014 to 2017 were enrolled in this study. The authors examined facial computed tomography, diplopia, extraocular muscle movement, and Hertel's exophthalmometer before and 6 months after surgery. The diplopia which was not recovered even at 6 months postoperatively was defined as persistent diplopia. Multivariable logistic regression analyses were performed on parameters that were found to be related to persistent diplopia using univariable logistic regression analyses. RESULTS: Univariable regression analysis showed that preoperative ocular motility limitation, preoperative diplopia, the type of fracture, the number of contacts with the fracture site and extraocular muscle (EOM), and EOM tenting were associated with persistent postoperative diplopia. Multivariable regression analysis using the previously mentioned five parameters showed 28.3-fold and 17.4-fold greater probabilities of diplopia after surgery in preoperative diplopia and EOM tenting, respectively (p = 0.023). CONCLUSIONS: Preoperative diplopia and EOM tenting were associated with persistent postoperative diplopia. These parameters were predictors of persistent diplopia in eyes with isolated inferior orbital wall fractures.