Moderate Elevation Research Articles

A-50 A Comprehensive Neuropsychological Case Study of a Child with Perinatal Hyperbilirubinemia

Abstract Objective Neonatal jaundice (hyperbilirubinemia) remains present in 60% of births in the United States1. Current literature links hyperbilirubinemia with neurodevelopmental problems, particularly with attention deficit hyperactivity disorder (ADHD), general learning difficulties, and non-progressive developmental delays. Moderate elevations in bilirubin are also suggested to increase the risk for cognitive, perceptual, motor, and auditory disorders. Imaging studies have shown selective patterns of injury to specific brain regions associated with deficits in executive function, including impulse control and working memory as well as different subtypes of attention problems grounded in reward circuitry system dysfunction in children with bilirubin encephalopathy. Method Neuropsychological functioning of a 12-year old Hispanic female with a history of high levels of perinatal bilirubin, and subsequent developmental and cognitive difficulties in speech, learning, attention and memory as well as problems with socialization and anxiety is presented with the purpose of adding to existing literature. Comprehensive neuropsychiatric interview and neuropsychological testing was completed. Results Results revealed several areas of neurocognitive weaknesses with deficits in areas of intellectual functioning, learning (reading and mathematics), expressive language, visual memory, attention, and auditory processing. Emotional and behavioral measures evidenced significant deficits in social-emotional functioning, particularly with interpersonal skills, sense of adequacy, and self-reliance, which resulted in increased anxiety contributing to cognitive and academic deficits. Conclusions Neuropsychological profile was consistent with cognitive, academic, behavioral and emotional manifestations theoretically associated with neuropathological findings in hyperbilirubinemia. Furthermore, similar to existing literature, cognitive deficits were observed in the absence of a clear cause of neonatal jaundice following a full-term, uncomplicated pregnancy.

Shifting Spatial and Temporal Patterns in the Onset of Seasonally Snow-Dominated Conditions in the Northern Hemisphere, 1972–2017

ABSTRACTThe potential for anthropogenic climate change to impact patterns of seasonal snow cover has motivated numerous studies seeking trends in its extent and duration. Many have been based on the NOAA-Rutgers record of Northern Hemisphere snow cover. Several studies have found augmented early-season snow identified from this archive to be anomalous, and related it to the introduction of higher-resolution imagery and a more automated interpretation process in 1999. This study contributes to the discussion by describing in greater detail the spatial and temporal distributions of trends in the onset of seasonally snow-dominated conditions between 1972 and 2017, and relationships to their physiographic and climatological contexts. It also identifies changepoints between negative and positive onset-date anomalies, and relates these to corresponding meteorological patterns. Most trends identified indicated earlier onset, and were associated with midlatitudes, low to moderate elevations, and colder, drier climates. These were situated largely northeast of major topographic chains, southwest of increasingly ice-free Arctic waters, and to the east of areas associated with blocking systems. Onset-date anomalies switched from positive to negative in approximately 70% of the affected points before 1997. These changepoints generally occurred earlier at higher elevations to the south and west, and later at lower elevations to the north and east. Overall temporal trajectories correspond broadly to shifts in temperature and precipitation over the same areas. In contrast, positive (later) onset trends were found over much smaller areas, associated with warmer, wetter climates and higher elevations, particularly on west-facing slopes; temporal variations in anomalies of their onset dates and associated meteorological conditions were distinct from those having negative trends.

Liver enzyme profile and progression in association with thyroid autoimmunity in Graves' disease.

ObjectiveTo investigate the associations of Graves' disease (GD) severity, autoimmunity and longitudinal liver enzyme changes with time in a cohort with well‐characterized GD.DesignRetrospective cohort study.PatientsPatients diagnosed with Graves' disease, treated at Royal Prince Alfred Hospital Sydney, Adult Thyroid Clinic from 2000 to 2012 inclusive.MeasurementsInclusion criteria were patients with a complete set of TSH, FT4, FT3, liver enzymes and TSH receptor antibody (TRAb) results prior to commencement of thionamide therapy.ResultsOf the 146 patients who had complete results, 69 (47%) had at least one abnormal liver enzyme. Gamma glutamyltransferase (GGT) was most frequently abnormal (74%), followed by alanine aminotransferase (ALT) (57%), alkaline phosphatase (ALP) (39%) and then aspartate aminotransferase (AST) (29%). Subsequent to thyroid function normalization, 78% of the liver enzymes were normalized, 10% were persistently abnormal and 12% were lost to follow‐up. Circulating TRAb, FT3 and FT4 results were categorized into mild, moderate and severe elevations. At univariate regression analyses, TRAb, FT3 and FT4 levels were each significantly associated with abnormal liver enzyme profile. Multivariate regression including TRAB, FT3 and FT4 as independent variables demonstrated FT3 and FT4 were more strongly associated with abnormal liver profile than TRAb. However, the initial FT3 and FT4 levels were not associated with abnormal liver profile in the subgroup with persistently abnormal liver profile.ConclusionGraves' disease is commonly associated with abnormal liver enzymes, and most commonly with abnormal levels of GGT, and that an abnormal liver enzyme profile is more directly linked to the degree of thyrotoxicosis than levels of TRAB.

Serum Vitamin D is Differentially Associated with Socioemotional Adjustment in Early School-Aged Ugandan Children According to Perinatal HIV Status and In Utero/Peripartum Antiretroviral Exposure History.

An impact of vitamin D in neurocognitive function has been theorized but it remains unknown whether vitamin-D insufficiency (VDI) is associated with worse socio-emotional adjustment (SEA) in vulnerable early school-aged children. This study examines the thesis that deficits in SEA are related to VDI using longitudinal data from 254 children that are perinatally HIV-infected (PHIV), exposed-uninfected (HEU), or unexposed-uninfected (HUU). In utero/peripartum antiretroviral (IPA) exposure was established per medical record documentation of biological mother’s ART regimen in pregnancy. Four caregiver-reported age- and sex-standardized measures of SEA were obtained at months 0, 6, and 12 for dependent children aged 6–10 years: externalizing problems (EPC), internalizing problems (IPC), behavioral symptoms index (BSI), and adaptive skills index (ASI). VDI was highly prevalent (74%, n = 188), and its association with change in SEA measures over 12 months varied by HIV-status (VDI*HIV, all p-values < 0.03). There was further variation in relationship of vitamin-D to SEA by IPA among PHIV (for ASI, BSI, and EPC, vitamin-D*IPA, p-value ≤ 0.01) and HEU (for BSI and EPC, vitamin-D*IPA, p-value ≤ 0.04). Among HUU, BSI (β = −0.32, 95% CI: −0.50, −0.13), IPC (β = −0.28, 95% CI: −0.47, −0.09), and EPC (β = −0.20, 95% CI: −0.37, −0.02) all declined moderately per quartile increment in VD. Among PHIV, on the one hand higher vitamin D predicted ASI gains (moderate vs. low VD, β = 0.52, p = 0.002), but this protective association was absent for BSI, EPC, and IPC (β = 0.36–0.77, p < 0.05). In absence of IPA-exposure, increasing vitamin-D predicted declines in BSI and EPC (moderate vs. low Vitamin D, β = −0.56 to −0.71, p ≤ 0.02) among HEU. However, given IPA exposure among HEU, higher VDI predicted moderate elevation in BSI (β = 0.39, 95% CI: 0.00, 0.78) and IPC (β = 0.48, 95% CI: 0.05, 0.92). Interaction between VD and IPA exposure for SEA outcomes among HEU and PHIV children warrants further investigation. The vitamin-D associated SEA improvement among HUU and HEU without IPA exposure suggests vitamin-D supplementation may remediate behavioral and adaptive deficits in this groups.

Long-term isotretinoin use does not cause parenchymal liver change: Ultrasonographic study in 50 patients.

The effect of isotretinoin on liver enzymes and lipid profile is reported as rare and reversible. However, possible parenchymal liver changes have not been demonstrated so far. The aim of this study was to evaluate the ultrasonography findings of the liver in patients receiving long-term isotretinoin therapy. We examined ultrasonographic findings of the liver together with serum alanin aminotransferase (ALT), aspartate aminotransferase (AST), and total cholesterol and triglyceride levels in 50 consecutive patients who have taken isotretinoin 10-40 mg daily for at least 6 months between January and December 2017. Of 50 patients examined, 40 were female, 10 were male. Mean age of the patients was 24.8 years. Five patients aged between 42 and 62 were found to have Grade 1 hepatosteatosis. Despite a moderate elevation, serum ALT, AST, and total cholesterol and triglyceride levels were in normal range in these five patients. Moreover, one patient had elevated ALT, and one another patient had elevated triglyceride level although both have normal liver ultrasonographic findings. Isotretinoin did not cause parenchymal liver changes as well as serum ALT, AST, and total cholesterol and triglyceride levels in patients who take it 10-40 mg daily for at least 6 months.

18F-PI2620 TAU-PET IN PROGRESSIVE SUPRANUCLEAR PALSY: A MULTI-CENTER EVALUATION

Progressive supranuclear palsy (PSP) is a 4-repeat (4R) tauopathy and region-specific tau deposits establish the neuropathological diagnosis of “definite PSP” post mortem. Future interventional trials against tau in PSP would strongly benefit from biomarkers to validate the specific presence of the target before therapy initiation. The novel second generation tau-PET ligand 18F-PI2620 proved absent off-target binding to monoamine oxidases and high affinity to 3/4R tau in Alzheimer's disease (AD). The aim of this multicenter-evaluation was to investigate 18F-PI2620 in patients with suspected 4R tau pathology in clinically diagnosed PSP. Eighteen patients (70±6y, n=9 female) with probable or possible PSP Richardson syndrome according to MDS-PSP criteria underwent 18F-PI2620 PET at four different centers together with ten healthy controls and ten disease controls (Multi-system atrophy, Parkinson's disease, and AD). Standardized uptake value ratios (SUVr, 30-60min) of predefined subcortical brain regions were generated using cerebellar scaling. SUVr data were compared between PSP, HC, and disease controls. Statistical parametric mapping (SPM, V12) was performed between PSP and HC. SUVr and SPM data were corrected for different centers. An in vitro pilot autoradiography using 18F-PI2620 incubation of brain slices was performed. Elevated 18F-PI2620 SUVr was observed in PSP patients (PSP rating scale: 40±17; range 13-71) in the globus pallidus (1.34±0.16; p=0.001; d=1.72) and the substantia nigra (1.33±0.13; p=0.002; d=1.52) when compared to HC (1.12±0.09/1.15±0.08). Disease controls showed a similar signal in the globus pallidus (1.12±0.08; p=n.s.) and a moderate elevation in the substantia nigra (1.25±0.10; p=n.s.) when compared to HC. SPM revealed elevated 18F-PI2620 uptake in the globus pallidus, in the substantia nigra, and frontal and parietal cortices (all p<0.001, uncorrected) as compared to HC. Subjects with low disease severity (PSP rating scale ≤30; n=4) already had a significantly elevated 18F-PI2620 uptake in the globus pallidus when compared to HC (1.38±0.13; p=0.001; d=2.32). Preliminary in vitro autoradiography showed distinguishable 18F-PI2620 binding in the globus pallidus of a PSP patient which was however lower when compared to cortical binding in AD.

Cross-border acquisitions and family businesses

Purpose The purpose of this paper is to shed light on the propensity of family firms to join a cross-border acquisition as acquirers. Design/methodology/approach The present study analyzes a sample of 270 acquisitions in the period 2015–2017 whose acquiring firms are represented by family and nonfamily listed European firms. Findings The results point out that family firms are less likely to make a cross-border acquisition than nonfamily counterparts. Research limitations/implications Mergers and acquisitions (M&amp;A) activity is cyclical by nature, represented by waves of concentrated intensity rather than necessarily by constant activity over time. Therefore, the main limitation is represented by the period analyzed (2015–2017), which restricts the possibility of seizing a greater number of transactions. Practical implications If careful evaluation leads to the consideration of M&amp;A as the optimal mode of entry into a certain foreign market, family firms should broaden the pool from which managers are selected in order to access more qualified staff, who are able to face international M&amp;As. Originality/value In recent years, a growing body of literature has focused on the effects of family ownership on the propensity of making an M&amp;A, on the method of payment chosen by an acquired family firm, and on the reaction of the market at the announcement of a family business’ M&amp;A. However, despite of the relevance of the entry modes of firms’ internationalization strategies, scant attention has been devoted to cross-border M&amp;As conducted by family firms, which occur when a family firm acquires a firm located in a foreign country. In order to fill the research gap, this work investigates the likelihood of a family firm’s acquisition of a foreign target.

TNFSF/TNFRSF cytokine gene expression in sickle cell anemia: Up-regulated TNF-like cytokine 1A (TL1A) and its decoy receptor (DcR3) in peripheral blood mononuclear cells and plasma

BackgroundSickle cell anemia (SCA), a disorder with an important inflammatory component, where vasoocclusion is major contributor to the disease pathophysiology. Pro-inflammatory cytokines play an important regulatory role in the process of inflammation. We investigated the expression TL1A/DR3/DcR3 cytokine signaling pathway in peripheral blood mononuclear cells (PBMC) and their corresponding plasma levels in SCA subjects who presented with acute painful episodes. Materials and methodsPBMC were isolated from the blood of SCA subjects and normal healthy controls. RNA isolated from PBMC was used for real time gene expression of TL1A/DR3/DcR3. Gene expression was compared in subgroups within SCA subjects with co-inherited fetal hemoglobin (HbF) or alpha-globin gene deletions. Plasma prepared from blood was used for determination of TL1A/DR3/DcR3 proteins by ELISA assays. ResultsIn the PBMC of SCA subjects, expression of TL1A and DcR3 is elevated, while DR3 expression is lowered in comparison to normal control PBMC. In SCA subjects with HbF > 10%, TL1A/DcR3 expression is lower, while HbF < 10% is associated with increased TL1A/DcR3 expression. Moreover, subjects with HbF > 10% appear to have significantly fewer pain episodes in comparison to those with HbF < 10%. Deletion of alpha-globin genes appears to have no significant effect on TL1A/DR3/DcR3 expression. Circulating levels of TL1A, DR3 and DcR3 in plasma were significantly elevated in SCA subjects. ConclusionsElevated TL1A and DcR3 expression in PBMC of SCA subjects during painful vasoocclusive crisis, suggest an altered TL1A expression may contribute to the pathophysiology of vasoocclusive crisis in SCA. HbF > 10% appears to moderate TL1A elevation, while HbF < 10% exacerbates TL1A/DcR3 responses. Furthermore, subjects with HbF > 10% have significantly lower pain episodes reported as compared to subjects with HbF < 10%.

Beauveria species diversity in the Gaoligong Mountains of China

The Gaoligong Mountains accommodate diverse ecosystems and biological resources. Beauveria species diversity is inventoried in seven vegetation types of the Gaoligong Mountains along an elevation gradient from 600 to 3800 m. Strains were isolated from soil by using Tenebrio molitor larvae as baits and from naturally occurring insect cadavers carrying anamorphic or teleomorphic fruiting structures of Beauveria spp. The 231 isolated Beauveria strains were identified based on molecular phylogenetic analyses inferred from Bloc, nrSSU, nrLSU, TEF, RPB1, and RPB2 sequences. Eleven species were identified as Beauveria asiatica, B. bassiana, B. brongniartii, B. caledonica, B. medogensis, B. pseudobassiana, and B. sinensis, previously recorded in other Chinese environments, and B. baoshanensis sp. nov., B. malawiensis, B. rudraprayagi, and B. yunnanensis sp. nov., encountered in China for the first time. Species phylogenies are presented and morphological characters of the new species are described. Most isolates were identified as B. bassiana and B. pseudobassiana (86.1%), while the other nine species were isolated rarely. Beauveria was widely distributed in six vegetation types, but not in the vegetation type of the highest altitude. More than four species were encountered in vegetation types with moderate elevation, and these environments also showed highest diversity of plants and insects.

Changes in vessel density of the patients with narrow antenior chamber after an acute intraocular pressure elevation observed by OCT angiography

BackgroundAlthough the pathogenesis of glaucoma is not fully understood,an elevated intraocular pressure (IOP) is a major factor contributing to its development and progression. The aim of this study was to investigate the changes in the vessel densities of the macula and optic nerve head (ONH) after an acute elevation in the intraocular pressure (IOP) observed using optical coherence tomography angiography (OCTA).MethodsThis was a prospective comparative study of subjects with narrow anterior chamber angles who underwent laser peripheral iridotomies (LPIs). The IOP was measured before and one hour after the LPI. The retinal vessel densities of the macula and ONH were measured using OCTA at the baseline and one hour after the LPI.ResultsA total of 64 eyes of 51 individuals were enrolled in this study, and 58 eyes of 43 individuals finally completed the study with a mean IOP rise of 10.5 ± 7.6 mmHg after the LPI. Based on the magnitude of the rise in the IOP, we divided the subjects into three groups: group A = IOP rise ≤10 mmHg, group B = 10 mmHg < IOP rise ≤20 mmHg, and group C = IOP rise > 20 mmHg. The vessel density did not differ after the acute IOP elevation in either the macular region or papillary region in group A or group B (p > 0.05), but there was a significant difference in group C (p < 0.05). However, when the subjects were not separated into groups, the vessel densities of the ONH and macular region did not differ between the measurements obtained at the baseline and one hour after the LPI (p > 0.05). The correlation existed in peripapillary and macular vessel density (p < 0.05).ConclusionIn these subjects with narrow antenior chamber, an acute mild or moderate IOP elevation for one hour after the LPI did not affect the vessel density in the macula or ONH, as examined using OCTA. However, when the IOP rise was greater than 20 mmHg, the macular and papillary vessel density decreased significantly.

A new species of Micryletta frog (Microhylidae) from Northeast India.

We describe a new species of frog in the microhylid genus Micryletta Dubois, 1987 from Northeast India based on molecular and morphological evidence. The new species, formally described as Micryletta aishani sp. nov., is phenotypically distinct from other congeners by a suite of morphological characters such as brown to reddish-brown dorsum; dorsal skin shagreened with minute spinules; snout shape nearly truncate in dorsal and ventral view; a prominent dark streak extending from tip of the snout up to the lower abdomen; ash-grey mottling along the margins of upper and lower lip extending up to the flanks, limb margins and dorsal surfaces of hand and foot; tibiotarsal articulation reaching up to the level of armpits; absence of outer metatarsal tubercles; and absence of webbing between toes. Phylogenetic relationships within the genus are inferred based on mitochondrial data and the new taxon is found to differ from all the recognised Micryletta species by 3.5–5.9% divergence in the mitochondrial 16S rRNA. The new species was found in the states of Assam, Manipur, and Tripura, from low to moderate elevation (30–800 m asl) regions lying south of River Brahmaputra and encompassing the Indo-Burma Biodiversity Hotspot. The discovery validates the presence of genus Micryletta in Northeast India based on genetic evidence, consequently confirming the extension of its geographical range, westwards from Southeast Asia up to Northeast India. Further, for nomenclatural stability of two previously known species, Microhyla inornata (= Micryletta inornata) and Microhyla steinegeri (= Micryletta steinegeri), lectotypes are designated along with detailed descriptions.

Intracameral injection of a chemically cross-linked hydrogel to study chronic neurodegeneration in glaucoma

Investigation of neurodegeneration in glaucoma, a leading cause of irreversible blindness worldwide, has been obfuscated by the lack of an efficient model that provides chronic, mild to moderate elevation of intraocular pressure (IOP) with preservation of optical media clarity for long term, in vivo interrogation of the structural and functional integrity of the retinal ganglion cells (RGCs). Here, we designed and formulated an injectable hydrogel based on in situ cross-linking of hyaluronic acid functionalized with vinyl sulfone (HA-VS) and thiol groups (HA-SH). Intracameral injection of HA-VS and HA-SH in C57BL/6J mice exhibited mild to moderate elevation of IOP with daily mean IOP ranged between 14 ± 3 and 24 ± 3 mmHg, which led to progressive, regional loss of RGCs evaluated with in vivo, time-lapse confocal scanning laser ophthalmoscopy; a reduction in fractional anisotropy in the optic nerve and the optic tract projected from the eye with increased IOP in diffusion tensor magnetic resonance imaging; a decrease in positive scotopic threshold response in electroretinography; and a decline in visual acuity measured with an optokinetic virtual reality system. The proportion of RGC loss was positively associated with the age of the animals, and the levels and the duration of IOP elevation. The new glaucoma model recapitulates key characteristics of human glaucoma which is pertinent to the development and pre-clinical testing of neuroprotective and neuroregenerative therapies. Statement of SignificanceA new model to study chronic neurodegeneration in glaucoma has been developed via intracameral injection of a specifically designed hyaluronic acid functionalized with vinyl sulfone and thiol groups for cross-linking. Intracameral injection of the chemically cross-linked hydrogel generates mild to moderate IOP elevation, resulting in progressive degeneration of the retinal ganglion cells, optic nerve, and optic tract, and a decline in visual function. The model recapitulates the key features of neurodegeneration in human glaucoma, which will facilitate and expedite the development of neuroprotective and neuroregenerative therapies.

180-OR: Tissue-Specific Functions of PPARα Overexpression in Liver, Adipose, and Pancreatic ß Cells

Peroxisome proliferator-activated receptor (PPAR) α is one of the master regulators of lipid metabolism and the major target of fibrates, a class of drugs improving dyslipidemia in metabolic syndromes. To understand the tissue-specific roles of PPARα and the coordination among multiple organs, we employed newly generated mouse models enabling doxycycline-inducible overexpression of PPARα specifically in liver, adipose or the insulin-producing pancreatic β-cells. Titrated by doxycycline dose, a moderate elevation of PPARα proteins in liver activated the transcription of its target genes. In mice with diet-induced obesity, hepatic overexpression of PPARα significantly reduced steatosis and improved systemic insulin sensitivity. Surprisingly, systemic triglyceride clearance was dramatically impaired, associated with a trend towards faster VLDL secretion. PPARα overexpression in adipose tissues had a marginal effect on systemic insulin sensitivity. However, inflammation was markedly ameliorated in white but not brown fat pads. Pancreatic β-cell-specific overexpression of PPARα resulted in a significant decrease in glucose-stimulated insulin secretion, suggesting a negative impact of PPARα induction on β-cell function. Taken together, our findings reveal the differential actions of enhanced PPARα on local tissues and whole-body metabolism and call for caution to the potential adverse effects from fibrate treatment. Further dissection of PPARα signaling with our mouse models may facilitate the discovery of novel therapeutic targets with high efficacy and specificity. Disclosure R. Ye: None. P.E. Scherer: None. Funding National Institutes of Health (R01DK55758, R01DK099110, P01-DK088761-01); JDRF (17-2012-36); Novo Nordisk Foundation (to P.E.S.)

Relevance of the assessment mode in the digital assessment of processing speed

ABSTRACTIntroduction: Many medical facilities and research institutes start using digital assessment methods to assess cognitive abilities, such as processing speed, instead of the traditional pen and paper versions. Even though many of the new digital assessment methods have shown to have a stable internal validity, the comparability of results across assessment modes is unclear. The study investigated whether results for assessing processing speed via (i) the traditional pen and paper version, (ii) a tablet and pen version, and (iii) a tablet and finger version are comparable.Methods: In a within-subject design, each participant (N= 30) completed the 90-number version by Oswald and Roth (1987) of the trail-making test (TMT) in three different assessment modes in randomized order. Each participant completed four TMT versions in each assessment mode (3 × 4 within-subject design).Results: Repeated measures ANOVA and mixed-effects analyses adjusted for age, gender, mode order, and trial number reveal significantly faster test TMT completion times (about 5 s) for the tablet and pen version compared to the pen and paper and the tablet and finger version.Conclusions: Our findings indicate that assessing processing speed can lead to different results with different digital versions depending on their setup, especially different input devices. Medical professionals and researchers who use digital assessment methods to assess cognitive abilities need to be aware of mode effects, even within the digital assessment domain, because the results may not be comparable and the available norms may not be applicable.

Predictors of neoadjuvant chemotherapy efficacy in localized pancreatic head cancer: A 15-year experience at a high volume pancreatic cancer center.

e15724 Background: Surgery followed by adjuvant chemotherapy (SF) is the standard approach for localized pancreatic adenocarcinoma (PC). Although neoadjuvant chemotherapy (NC) is being increasingly used, its efficacy remains debatable. This study aims to identify baseline factors associated with benefit from NC as compared to SF for PC. Methods: Review of a prospectively maintained database of resected localized head PC undergoing NC or SF at a tertiary referral hospital from 2002 to 2018. Baseline factors investigated included clinical stage by EUS (7th edition AJCC), CT vessel involvement, and serum CA19-9. Baseline CA19-9 levels were grouped into mild (37-200), moderate (200-900), and marked elevations (≥ 900). Patients with baseline serum CA19-9 &lt; 37 IU/dL were excluded from the analysis. Results: In total, 269 patients were evaluated: 165 (61%) received NC and 104 (39%) had SF. Mean patient age was 68.3 years and 50% were females. Of these, 42% had stage IIB, 44% had N1 disease, and 38% had vascular involvement. Compared to SF approach, NC was associated with improved median survival for CA19-9 of &lt; 200 IU/dL (30 vs 21 months, p = 0.08), 200-900 IU/dL (32 vs 17 months, p &lt; 0.01), and the ≥900 IU/dL (33 vs 12 months, p &lt; 0.01) groups. On Cox regression, NC was the only baseline factor predictive of improved survival in the groups with moderate (HR:0.35,[95% CI:0.20-0.62];p &lt; 0.01) and marked (HR:0.36,[95% CI:0.18-0.71];p &lt; 0.01) pretreatment CA19-9 elevation. Notably, NC was not predictive of improved survival in the cohort with mild CA19-9 elevation. Conclusions: This study identifies a cohort of patients that benefits from neoadjuvant chemotherapy over a surgery first approach for localized pancreatic head cancer. Elevation in baseline CA19-9 may serve as the strongest indicator for chemotherapy before resection.

Safety and pharmacokinetics of BXQ-350 in a phase 1a and 1b trial of solid tumors and high-grade glioma.

e13531 Background: BXQ-350 is composed of the multifunctional, lysosomal-activator protein Saposin C and phosphatidylserine lipid with demonstrated antitumor effects in vitro and in vivo. In this abstract we update the safety and pharmacokinetic (PK) profile based on an ongoing Phase 1 trial. Methods: BXQ-350 was administered in a Phase 1a dose-escalation trial (NCT02859857), and an ongoing Phase 1b trial (data cut off at max of 6 cycles, 01DEC2018) to refractory solid tumor/high-grade glioma patients (pts). In Phase 1a, pts received escalating IV BXQ-350 doses of 0.7, 1.1, 1.4, 1.8, or 2.4 mg/kg on days 1, 2, 3, 4, 5, 8, 10, 12, 15, 22 (cycle 1), 29 (cycle 2), and thereafter 28-day cycles. PK was assessed over a 24-hr period following the first dose. The Saposin C level was analyzed by ELISA and PK parameters were calculated using noncompartmental methods. Results: The 1a cohort of 18 pts (age 24-69) had a median of 3 cycles and 1b cohort of 20 pts (age 31-80) had median of 2 cycles with no treatment-related serious adverse events to date. Moderately severe related adverse events (AEs, n case, n events) are reported with serious non-related events. The most common treatment-related AE was fatigue (2 at dose 1.1, 2 at 1.8, 1 at 2.4mg/kg and 3 in 1b), at 2.4 mg/kg, 1 pt had moderate blood pressure elevation. Exposures in the 1.4 and 1.8 mg/kg cohorts were less than dose-proportional, likely due to higher clearance in those groups. The overall mean clearance and half-live values were 66.8 (mL/kg/h) and 4.03 h, respectively. Conclusions: BXQ-350 has had no serious related AEs during dose-escalation or in the on-going trial supporting a tolerable safety profile at 2.4 mg/kg. Clinical trial information: NCT02859857. [Table: see text]

Minimize the regular laboratory monitoring during the systemic isotretinoin treatment: data of 704 patients with acne vulgaris

Backround: Despite extensive usage of systemic isotretinoin in patients with acne for many years, laboratory monitoring protocols for adverse effects depend on the centers and there is no standardized practice for frequency and type of laboratory testing. We aimed to decrease unnecessary monitoring and to standardize our general clinical practice of our department as well as to provide patient comfort and cost saving.Materials and methods: The medical charts of 704 acne patients treated with systemic isotretinoin were reviewed retrospectively. The National Cancer Institute common terminology criteria for adverse events v3.0 grading system was used in order to categorize the laboratory abnormalities of liver functions and lipid levels.Results: All laboratory abnormalities were grade I. Abnormal liver function was seen in 7.2% of the patients (n = 51), maximum values were ALT: 87 IU/L, AST: 97 IU/L (normal values, ALT: 5–41 IU/L, AST: 5–40 IU/L) and median time of the abnormalities in liver function tests was in the second month. Lipid profile abnormalities were detected in 58% of the patients (n = 401). Maximum values during the laboratory monitoring were Tg: 481 mg/dL CHOL: 314 mg/dL, LDL: 259 mg/dL (normal values, Tg: 0–200 mg/dL, CHOL.: 0–200 mg/dL, LDL: 0–100 mg/dL). The median time of lipid abnormalities was in the first month (1–3 months). Abnormalities related to CBC were seen in 8.2% of the patients (n = 58). The median time of CBC abnormality was the second month of treatment. Anemia, leukopenia and thrombocytopenia were seen in 3.4%, 3.7%, and 1.6% of the patients respectively.Conclusion: Clinically insignificant and reversible CBC abnormalities, mild to moderate elevation of liver transaminases and serum lipids are the most common laboratory abnormalities in patients with acne treated with oral isotretinoin. Due to these abnormalities are reversible even the isotretinoin therapy continued, and generally there is no need to discontinuation of treatment due to laboratory abnormalities, frequent biochemical monitoring is not recommended.

Meta-Analysis of Anxiety in Parents of Young People with Chronic Health Conditions.

Chronic health conditions are often associated with uncertainty and threats which may cause anxiety in the family members. The present meta-analysis analyzed whether parents of children with chronic physical diseases and/or sensory/physical disabilities show higher anxiety levels than parents of healthy/nondisabled children or test norms. The databases PSYCINFO, MEDLINE, Google Scholar, CINAHL, and PSYNDEX were searched for relevant studies. In total, 486 studies were identified that fulfilled the inclusion criteria. We found moderate elevations of anxiety symptoms in parents of young people with chronic conditions (g = .54 standard deviation units). About 16% of the parents fulfilled the criteria for an anxiety disorder. Parents of young people with neuromuscular disorders, HIV-infection/AIDS, and cancer during active treatment showed large elevations of anxiety symptoms. Elevations of anxiety symptoms were smaller in the cases of longer lasting chronic conditions, longer time since the end of active treatment, in families of older children, in samples with lower percentages of mothers, and in studies from economically developed countries compared to less developed countries. Measures for preventing and reducing anxiety symptoms in parents of young people with neuromuscular disorders, HIV-infection/AIDS, and those undergoing cancer treatments are particularly needed.

Long-Term Intravitreal Dexamethasone Implant Outcomes in Uveitis

ABSTRACTPurpose: To describe the long-term clinical outcomes in a cohort of uveitic eyes treated with the intravitreal dexamethasone implant (Ozurdex; Allergan, Inc).Methods: Seventy-nine (63 patients) receiving 134 implant injections over 82 months were included. Indication, visual acuity (VA), intraocular pressure (IOP), vitreous haze score (VHS), central retinal thickness (CRT), time to reinjection, systemic treatments, and complications data were recorded.Results: The cumulative probability of VA improvement was 80% at 1 month and 90% at 12 months, and it was maintained until 60 months. Eyes with baseline vitritis (VHS >0.5; 68%) had a probability of VHS improvement of 33% at 1 month, 75% at 12 months, and 85% at 60 months. The probability of CRT improvement was 33% at 1 month, 75% at 12 months, and 85% at 60 months. The most frequent adverse event was moderate IOP elevation (≥25 mmHg) in 30.3%, no cases of retinal detachment or endophthalmitis were observed.Conclusions: The dexamethasone implant provides favorable VA, CRT, and VHS long-term outcomes in uveitis with a reduced rate of severe adverse events.

Twenty-Five Years of Biochemical Diagnosis of Gaucher Disease: The Egyptian Experience

Background: Gaucher disease is a rare multi-systemic metabolic disorder resulting from the deficiency in β-glucocerebrosidase enzyme, with consequent accumulation of glucocerebroside. Less than 15% of mean normal activity β-glucocerebrosidase in leukocytes is the gold standard for the diagnosis of Gaucher disease, which is supplemented by a massive elevation in chitotriosidase enzyme activity. We report here our experience in the biochemical diagnosis of Gaucher disease by showing the variability and the heterogeneity of the activity of enzymes over 25 years from 1993-2017, through referring 5128 clinically suspected Gaucher disease cases to our Biochemical Genetics Department, National Research Centre, as the main reference lab in Egypt for the diagnosis of Inherited Metabolic Disorders. Methods: β-glucosidase enzyme activity and chitotriosidase were done to all referred cases. Sphinogmylinase activity was estimated for all cases with normal activity of β- glucosidase and moderate elevation of chitotriosidase. Results: Out of the 5128 suspected cases, 881 (17%) had deficiency in β-glucocerebrosidase activity, accompanied with high chitotriosidase activity level, ranges (213-66700 μmol/l/h) and mean (7254.8 μmol/l/h). Zero chitotriosidase activity is found in 9 patients (1%) with low β-glucosidase. 451 cases were diagnosed as Niemann Pick patients (8.8%). Discussion and Conclusion: Other biochemical markers are needed in addition to chitotriosidase enzyme for the diagnosis. Molecular testing was done in relatively small numbers and need to be available parallel with biochemical testing.