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Chrysanthemum white rust (CWR), caused by Puccinia horiana, is pathogenic on many Chrysanthemum spp. and close relatives, and infects commercially important florist chrysanthemum cultivars (Chrysanthemum × morifolium) throughout the world. Due to regulations, most research and observations with CWR are done in vitro with symptomatic plants. In contrast, research presented herein is based on microscopic examination of symptomatic and asymptomatic plants collected from natural outbreaks in the field. We observed scattered (not in a linear pattern) telial sori on infected chrysanthemum leaves, stems, and flowers that coalesced at high infection levels. Teliospores were mainly two-celled but occasionally one- or three-celled. Promycelia arose from the apical teliospore cell, the basal cell, or both. The number of basidiospores on promycelia varied from one to four. Germ tubes, arising from P. horiana basidiospores, penetrated the host epidermis directly without appressoria. A mucilaginous exudate formed at the site of attachment and penetration of leaf and stem tissue, as well as on internal cell walls. P. horiana colonization was systemic, with intercellular mycelium and intracellular M-haustoria in both symptomatic and asymptomatic infected host tissue. Hyphal anastomosis was observed within infected plants, suggesting that asexual fusion between different P. horiana pathotypes or genotypes might occur. [ABSTRACT FROM AUTHOR]

Our aim is to report methodology that has been developed to calibrate and verify PET and SPECT quantitative image accuracy and quality assurance for use with nonstandard radionuclides, especially with longer half-lives, in clinical imaging trials. Methods: Procedures have been developed for quantitative PET and SPECT image calibration for use in clinical trials. The protocol uses a 3-step approach: check quantitative accuracy with a previously calibrated radionuclide in a simple geometry, check the novel trial radionuclide in the same geometry, and check the novel radionuclide in a more challenging, complex geometry (the National Electrical Manufacturers Association [NEMA] NU-2 International Electrotechnical Commission [IEC] image-quality phantom). The radionuclides used in the trial as an example are 124 I (PET) and 131 I (SPECT). In both cases, whole-body tomographic SPECT and PET imaging with accompanying low-dose CT are required. PET accuracy is based on calibrating the dose calibrator to produce quantitative images for radionuclides other than 18 F, with all images reconstructed on each individual site's PET systems. For SPECT, an independent sensitivity measurement is made and then used to calibrate the SPECT images reconstructed at the core laboratory. After calibration, the final testing for both PET and SPECT uses the NEMA NU-2 IEC image-quality phantom to derive several metrics including quantitative accuracy based on an average SUV (SUV avg ). Results: Using the method described, 7 sites in Australia have been qualified for 10 PET/CT scanners using 124 I imaging and 8 SPECT/CT systems for 131 I. One PET/CT system was found to give a result outside the specification of an SUV avg of 1.0 ± 0.05. All SPECT/CT systems gave an SUV avg accurate to within ±10% (SUV mean , 1.0 ± 0.1) of the true value for reconstructed radioactivity concentration in Bq/cm 3 Conclusion: A general methodology has been developed to calibrate and validate PET and SPECT systems for quantitative imaging in clinical trials. The preparation of the test objects and the procedures is relatively simple and can generally be implemented by the staff at the site of the imaging center with the equipment supplied by the clinical trials organization., (© 2025 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: The introduction of therapeutics for Alzheimer's disease has led to increased interest in precisely quantifying amyloid-β (Aβ) burden for diagnosis, treatment monitoring, and further clinical research. Recent positron emission tomography (PET) hardware innovations including digital detectors have led to superior resolution and sensitivity, improving quantitative accuracy. However, the effect of PET scanner on Centiloid remains relatively unexplored and is assumed to be minimized by harmonizing PET resolutions., Objective: To quantify the differences in Centiloid between scanners in a paired cohort., Methods: 36 participants from the Australian Imaging, Biomarker and Lifestyle study (AIBL) cohort were scanned within a year on two scanners. Each participant underwent 18 F-NAV4694 imaging on two of the three scanners investigated, the Siemens Vision, the Siemens mCT and the Philips Gemini. We compared Aβ Centiloid quantification between scanners and assessed the effectiveness of post-reconstruction PET resolution harmonization. We further compared the scanner differences in target sub-regions and with different reference regions to assess spatial variability., Results: Centiloid from the Vision camera was found to be significantly higher compared to the Gemini and mCT; the difference was greater at high-Centiloid levels. Post-reconstruction resolution harmonization only accounted for and corrected ∼20% of the Centiloid (CL) difference between scanners. We further demonstrated that residual differences have effects that vary spatially between different subregions of the Centiloid mask., Conclusions: We have demonstrated that the type of PET scanner that a participant is scanned on affects Centiloid quantification, even when scanner resolution is harmonized. We conclude by highlighting the need for further investigation into harmonization techniques that consider scanner differences., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Numerous feeding strategies have been used to mitigate the catabolism of major burn injury. Whether higher energy and/or protein delivery results in better long-term outcomes is unknown., Methods: We performed a secondary analysis of data from adults with major burn injuries enrolled in the Randomized Trial of Enteral Glutamine to Minimize the Effects of Burn Injury at 54 burn centers in 18 countries. The sample was restricted to those who were mechanically ventilated within 72 hours of injury and for ≥7 days. Our key exposure was adequacy of energy, and protein ([Delivered i /Prescribed i ] × 100) was categorized into three groups each: low, 0% to 50%; moderate, ≥50% to 79%; and high, ≥80%. We also analyzed adequacy using restricted cubic splines. Primary and secondary outcomes included 6-month mortality and functional outcomes (i.e., 36-Item Short-Form Health Survey, Katz Index of Independence in Activities of Daily Living, Lawton Activities of Daily Living scores), respectively. Regression models were adjusted for age, body mass index, Charlson Comorbidity Index, baseline Acute Physiology and Chronic Health Evaluation II and modified Sequential Organ Failure Assessment scores, burn size, energy/protein adequacy, and study site., Results: A total of 493 participants met the cohort restriction criteria; 336 participants were alive at 6 months. 36-Item Short-Form Health Survey, Katz Index of Independence in Activities of Daily Living, and Lawton Instrumental Activities of Daily Living Scale were completed by 218, 216, and 215 participants, respectively. The mean ± SD age was 48 ± 17 years, and 74% were male. The mean ± SD burn size was 41% ± 18% total body surface area. Participants who received 25% of recommended calories had nearly four times the hazard of death during the 6-month follow-up period than participants who received 100% of prescribed calories (adjusted hazard ratio, 3.89; 95% confidence interval, 1.35-11.20) ( p = 0.02). There was no significant association between protein and 6-month mortality or energy/protein delivery and 6-month functional outcomes., Conclusion: There was a positive association between higher doses of energy and 6-month survival. This relationship conflicts somewhat with several energy studies among critically ill and non-burn-injured patients. The lack of consistent evidence on optimal nutrition for critically injured patients, a fundamental component of burn care, suggests potential for a randomized trial of lower versus higher energy to improve long-term outcomes after burn injury., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To compare visual outcomes, ocular complications and therapies for patients with scleritis-associated intraocular inflammation (SAI) and patients with isolated scleritis (IS)., Results: A total of 52 patients (36 with SAI and 16 with IS) were reviewed. Mean age (standard deviation) at presentation was 48.4 years old (± 15.4) in the SAI group and 53 years old (± 17.1) in the IS group (p = .37). Visual acuity was worse at presentation and last visit for patients with SAI compared to IS (p = .04). Patients in the SAI group developed greater posterior segment complications than in the IS group (p = .002)., Conclusions: Scleritis with intraocular inflammation was associated with a higher rate of visual morbidity compared to isolated scleritis. More aggressive management strategies may be needed for patients who present with scleritis associated with inflammation.

Purpose: To explore characteristic imaging features of nonparaneoplastic autoimmune retinopathy (npAIR) to augment diagnostic criteria., Methods: This is a retrospective cohort study of patients with npAIR evaluated at the Emory Eye Center between 2013 and 2019. Multimodal fundus images were evaluated to characterize the evolution of the disease., Results: Twenty-one eyes of 12 patients were classified as having npAIR. Five patients (42%) were female, with median (range) age of 59 years (45-85 years). Median baseline visual acuity was 20/30 (20/20 to hand motions). Disease was asymmetric in 11 patients (92%). Common imaging findings included absence of bone spicules (86% of affected eyes), presence of attenuated vessels (86%), and speckled hypoautofluorescence in perimacular and perivenular regions. Three eyes were noted to present early with subtle splotchy fundus autofluorescence abnormality, ultimately developing characteristic speckled perimacular hypoautofluorescence. On optical coherence tomography, 18 eyes (86%) had loss of outer retinal bands with relative foveal sparing and a tapered transition zone., Conclusion: Many eyes with npAIR exhibit a subacute, asymmetric, generalized photoreceptor degeneration featuring outer retinal atrophy with relative foveal sparing, retinal vascular attenuation, absence of bone spicules, and speckled hypoautofluorescence often in a perimacular and perivenular distribution. Findings of this study augment diagnostic criteria to improve specificity and accessibility of testing for npAIR.

Introduction: Fatty liver disease (FLD) is associated with systemic inflammation, metabolic disease, and socioeconomic risk factors for poor health outcomes. Little is known on how adults with FLD recover from traumatic injury., Methods: We studied adults admitted to the intensive care unit of a level 1 trauma center (2016-2020), excluding severe head injury/cirrhosis (N = 510). We measured the liver-spleen attenuation difference in Hounsfield units (HU L-S ) using virtual noncontrast computerized tomography scans: none (HU L-S >1), mild (-10≤HU L-S <1), moderate/severe (HU L-S  < -10). We used Cox models to examine the "hazard" of recovery from systemic inflammatory response (SIRS score 2 or higher) organ dysfunction, defined as sequential organ failure assessment score 2 or higher, and lactate clearance (<2 mmol/L) in relation to FLD., Results: Fifty-one participants had mild and 29 had moderate/severe FLD. The association of FLD with recovery from SIRS differed according to whether an individual had shock on admission (hazard ratio [HR] = 0.76; 95% confidence interval [CI] 0.55-1.05 with shock; HR = 1.81; 95% CI 1.43-2.28 without shock). Compared to patients with no FLD, the hazard of lactate clearance was similar for mild FLD (HR = 1.04; 95% CI 0.63-1.70) and lower for moderate/severe FLD (HR = 0.40; 95% CI 0.18-0.89)., Conclusions: FLD is common among injured adults. Associations of FLD with outcomes after shock and critical illness warrant further study., (Published by Elsevier Inc.)

Purpose: To describe a unique indocyanine green angiography (ICGA) feature in sarcoidosis-associated choroidal vasculitis in a 33-year-old woman., Methods: Case report., Results: A 33-year-old woman with sarcoidosis was referred for the evaluation of blurry vision in both eyes. On ocular examination of both eyes, slit-lamp biomicroscopy and ophthalmoscopy revealed 0.5+ anterior chamber cell, 1+ vitreous cell, and no vitreous haze. Also noted were areas of venous perivascular sheathing and multiple (3-5) inferior snowballs. Fluorescein angiography showed optic disk hyperfluorescence, retinal phlebitis, and hyperfluorescence with late leakage in the periphery (Figure 1). Indocyanine green angiography showed small hypofluorescent spots. Also noted on the ICGA images were multiple, sharp, linear hyperfluorescent areas signifying areas of choroidal vasculitis (Figure 2). The patient was referred to rheumatology for the initiation of immunomodulatory therapy., Conclusion: To the best of our knowledge, this ICGA pattern of multiple, sharp, linear hyperfluorescent areas has not been previously described in patients with sarcoidosis. This ICGA pattern represents areas of sarcoidosis associated choroidal vasculitis.

Importance: Multiple classification methods are used to identify sepsis from existing data. In the trauma population, it is unknown how administrative methods compare with clinical criteria for sepsis classification., Objectives: To characterize the agreement between 3 approaches to sepsis classification among critically ill patients with trauma and compare the sepsis-associated risk of adverse outcomes when each method was used to define sepsis., Design, Setting, and Participants: This retrospective cohort study used data collected between January 1, 2012, and December 31, 2020, from patients aged 16 years or older with traumatic injury, admitted to the intensive care unit of a single-institution level 1 trauma center and requiring invasive mechanical ventilation for at least 3 days. Statistical analysis was conducted from August 1, 2021, to March 31, 2022., Exposure: Hospital-acquired sepsis, as classified by 3 methods: a novel automated clinical method based on data from the electronic health record, the National Trauma Data Bank (NTDB), and explicit and implicit medical billing codes., Main Outcomes and Measures: The primary outcomes were chronic critical illness and in-hospital mortality. Secondary outcomes included number of days in an intensive care unit, number of days receiving mechanical ventilation, discharge to a skilled nursing or long-term care facility, and discharge to home without assistance., Results: Of 3194 patients meeting inclusion criteria, the median age was 49 years (IQR, 31-64 years), 2380 (74%) were male, and 2826 (88%) sustained severe blunt injury (median Injury Severity Score, 29 [IQR, 21-38]). Sepsis was identified in 747 patients (23%) meeting automated clinical criteria, 118 (4%) meeting NTDB criteria, and 529 (17%) using medical billing codes. The Light κ value for 3-way agreement was 0.16 (95% CI, 0.14-0.19). The adjusted relative risk of chronic critical illness was 9.9 (95% CI, 8.0-12.3) for sepsis identified by automated clinical criteria, 5.0 (95% CI, 3.4-7.3) for sepsis identified by the NTDB, and 4.5 (95% CI, 3.6-5.6) for sepsis identified using medical billing codes. The adjusted relative risk for in-hospital mortality was 1.3 (95% CI, 1.0-1.6) for sepsis identified by automated clinical criteria, 2.7 (95% CI, 1.7-4.3) for sepsis identified by the NTDB, and 1.0 (95% CI, 0.7-1.2) for sepsis identified using medical billing codes., Conclusions and Relevance: In this cohort study of critically ill patients with trauma, administrative methods misclassified sepsis and underestimated the incidence and severity of sepsis compared with an automated clinical method using data from the electronic health record. This study suggests that an automated approach to sepsis classification consistent with Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) clinical criteria is feasible and may improve existing approaches to health services and population-based research in this population.

Background: Alaskan Native/American Indian (AI/AN) participation in biomedical sciences is often hindered by cultural miscommunication regarding concepts and definitions of health. Identifying culturally contextualized health priorities is crucial to building research collaborations between academic institutions and AI/AN consortia., Methods: This article describes pilot data from the development of a culture and wellness questionnaire deployed by the Great Lakes Native American Research Center for Health at cultural events and community engagement meetings. The questionnaire was designed in collaboration with AI/AN members to assess performance indicators of public health promotion in AI/AN populations who are culturally inclined to interpret health holistically., Results: There were 25 completed questionnaires. Connection to the land (88%) and "giving thanks" (96%) were the most prominently affirmed health and wellness concepts. Participants were least confident (33%) in the ability to support the next generation culturally (language, stories, etc). These results comport with anecdotal data that AI/AN concepts of health and wellness should be co-developed with AI/AN cultural leaders and community members. Future implications for academic partnerships are discussed., (Copyright© Board of Regents of the University of Wisconsin System and The Medical College of Wisconsin, Inc.)

Positron emission tomography is the imaging modality of choice when it comes to the high sensitivity detection of key markers of thrombosis and inflammation, such as activated platelets. We, previously, generated a fluorine-18 labelled single-chain antibody (scFv) against ligand-induced binding sites (LIBS) on activated platelets, binding it to the highly abundant platelet glycoprotein integrin receptor IIb/IIIa. We used a non-site-specific bio conjugation approach with N -succinimidyl-4-[ 18 F]fluorobenzoate (S[ 18 F]FB), leading to a mixture of products with reduced antigen binding. In the present study, we have developed and characterised a novel fluorine-18 PET radiotracer, based on this antibody, using site-specific bio conjugation to engineer cysteine residues with N -[2-(4-[ 18 F]fluorobenzamido)ethyl]maleimide ([ 18 F]FBEM). ScFv anti-LIBS and control antibody mut-scFv, with engineered C-terminal cysteine, were reduced, and then, they reacted with N -[2-(4-[ 18 F]fluorobenzamido)ethyl]maleimide ([ 18 F]FBEM). Radiolabelled scFv was injected into mice with FeCl 3 -induced thrombus in the left carotid artery. Clots were imaged in a PET MR imaging system, and the amount of radioactivity in major organs was measured using an ionisation chamber and image analysis. Assessment of vessel injury, as well as the biodistribution of the radiolabelled scFv, was studied. In the in vivo experiments, we found uptake of the targeted tracer in the injured vessel, compared with the non-injured vessel, as well as a high uptake of both tracers in the kidney, lung, and muscle. As expected, both tracers cleared rapidly via the kidney. Surprisingly, a large quantity of both tracers was taken up by organs with a high glutathione content, such as the muscle and lung, due to the instability of the maleimide cysteine bond in vivo, which warrants further investigations. This limits the ability of the novel antibody radiotracer 18 F-scFv anti-LIBS to bind to the target in vivo and, therefore, as a useful agent for the sensitive detection of activated platelets. We describe the first fluorine-18 variant of the scFv anti-LIBS against activated platelets using site-specific bio conjugation.

Purpose: Longitudinal evaluation of acute exudative polymorphous paraneoplastic vitelliform maculopathy (AEPPVM) following diagnosis and treatment of metastatic melanoma., Methods: Case report of a 47-year-old male with unknown primary metastatic melanoma and AEPPVM monitored before and during melanoma treatment using clinical exam, retinal imaging, and electroretinograms (ERG). Genetic testing and autoantibody panels were performed., Results: He presented within a month of metastatic melanoma diagnosis with numerous bilateral vitelliform lesions in the posterior pole, consistent with AEPPVM. Metastatic disease was treated with immunotherapy, radiosurgery, and radiation over 48 months. Maculopathy and metastatic disease improved and worsened in parallel. Genetic testing was negative for bestrophin-1. An autoantibody panel was positive for anti-recoverin and transducin-α., Conclusion: AEPPVM is an uncommon paraneoplastic retinopathy found in patients with metastatic malignancy. To our knowledge, this is the first report demonstrating a temporal association between metastatic disease activity and quantifiable changes in retinal imaging over a 4-year period.

Purpose: The mainstay empiric treatments of bacterial endophthalmitis are intravitreal vancomycin and ceftazidime. In the United States, up to 10% of the general population has a reported penicillin (PCN) allergy. Despite low cross-reactivity between PCN and later-generation cephalosporins, some providers alter the intravitreal antibiotic choice for endophthalmitis because of concern for allergic reactions. We evaluated the management strategies of infectious endophthalmitis in the setting of self-reported systemic antibiotic allergies and the association with adverse reactions after standard intravitreal antibiotic administration., Design: Single-center, retrospective cohort study., Participants: All patients with endophthalmitis between 2005 and 2019 and documented PCN, PCN-analog, cephalosporin, or vancomycin allergy who received intravitreal antibiotics on the basis of International Classification of Diseases 9th and 10th Revisions, and Current Procedural Terminology codes., Methods: Retrospective chart review., Main Outcome Measures: Any allergic reaction after intravitreal injection, additional surgical interventions required for treatment, and visual function at last recorded visit., Results: Of the 65 patients included in this cohort, the most common causes of endophthalmitis were postcataract extraction surgery (n = 23, 35.4%) and postintravitreal injection (n = 11, 16.9%). All patients (65/65) received intravitreal vancomycin, and 81.5% (53/65) received intravitreal ceftazidime. Of the 53 patients who received intravitreal ceftazidime, 46 (86.8%) had allergies to PCNs alone, 5 (9.4%) had a cephalosporin allergy alone, and 2 (3.8%) had reported allergies to both PCN and cephalosporin antibiotics. Two patients (3.1%) with a documented vancomycin allergy received intravitreal vancomycin without complication. No patients exhibited any systemic or local allergic reactions or complications after intravitreal injection., Conclusions: There were no documented allergic reactions in this cohort of patients with systemic antibiotic allergies who were treated for infectious endophthalmitis. Our findings are consistent with previous reports of a low allergic cross-reactivity between PCN and later-generation cephalosporins. Ophthalmologists should use evidence-based practices and a careful informed consent process when choosing intravitreal antibiotics for patients with specific antibiotic allergies. In the routine patient with suspected bacterial endophthalmitis, PCN allergy may not be an absolute contraindication to intravitreal cephalosporin use., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objectives: Chronic critical illness (CCI) is a phenotype that occurs frequently in patients with severe injury. Previous work has suggested that inflammatory changes leading to CCI occur early following injury. However, the modifiable factors associated with CCI are unknown. We hypothesized that hypothermia, an early modifiable factor, is associated with CCI., Methods: To determine the association of hypothermia and CCI, a secondary analysis of the Inflammation and Host Response to Injury database was performed, and subsequently validated on a similar cohort of patients from a single level 1 trauma center from January 2015 to December 2019. Hypothermia was defined as initial body temperature ≤34.5°C. CCI was defined as death or sustained multiorgan failure ≥14 days after injury. Data were analyzed using univariable analyses with Student's t-test and Pearson's χ 2 test, and logistic regression. An arrayed genomic analysis of the transcriptome of circulating immune cells was performed in these patients., Results: Of the initial 1675 patients, 254 had hypothermia and 1421 did not. On univariable analysis, 120/254 (47.2%) of patients with hypothermia had CCI, compared with 520/1421 (36.6%) without hypothermia who had CCI, p<0.001. On multivariable logistic regression, hypothermia was independently associated with CCI, OR 1.61 (95% CI 1.17 to 2.21) but not mortality. Subsequent validation in 1264 patients of which 172 (13.6%) were hypothermic, verified that hypothermia was independently associated with CCI on multivariable logistic regression, OR 1.84 (95% CI 1.21 to 2.41). Transcriptomic analysis in hypothermic and non-hypothermic patients revealed unique cellular-specific genomic changes to only circulating monocytes, without any distinct effect on neutrophils or lymphocytes., Conclusions: Hypothermia is associated with the development of CCI in severely injured patients. There are transcriptomic changes which indicate that the changes induced by hypothermia may be associated with persistent CCI. Thus, early reversal of hypothermia following injury may prevent the CCI., Level of Evidence: III., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine clinical course and outcomes in rheumatic disease patients with coronavirus disease 2019 (COVID-19) and compare results to uninfected patients., Methods: We conducted a case cohort study of autoimmune disease patients with COVID-19 (confirmed by severe acute respiratory syndrome coronavirus 2 PCR) from February 1, 2020, to July 31, 2020, and compared them in a 1:3 ratio with uninfected patients who were matched based on race, age, sex, and comorbidity index. Patient demographics, clinical course, and outcomes were compared among these patient groups., Results: A total of 70 rheumatic disease patients with COVID-19 (mean age, 56.6 years; 64% African American) were identified. The 34 (49%) patients who were hospitalized used oral glucocorticoids more frequently than those treated as outpatients (p < 0.01). All 10 patients using anti-TNFα medications were treated as outpatients (p < 0.01). Those hospitalized with COVID-19 more often required ICU admission (17 (50%) vs 27 (26%), p = 0.01) and intubation (10 (29%) vs 6 (6%), p < 0.01) than uninfected patients and had higher mortality rates (6 (18%) vs 3 (3%), p < 0.01). Of the six COVID-19 patients who died, only one was of African ancestry (p = 0.03)., Conclusion: Rheumatic disease patients infected with COVID-19 were more likely to require ICU admission, ventilation, and died more frequently versus uninfected patients with autoimmune disease. Patients on anti-TNFα medications were hospitalized less frequently, while those on chronic glucocorticoids were hospitalized more frequently. These findings have important implications for medication choice in rheumatic disease patients during the ongoing spread of COVID-19. Key Points • We show that hospitalized rheumatic disease patients with COVID-19 have poorer outcomes including ICU admission, ventilation, and death compared to hospitalized rheumatic disease patients not infected with COVID-19. • This study adds further support regarding protective effects of anti-TNFα medications in COVID-19 disease course, with 0 of 10 of these patients required hospitalization.

The purpose of this study was to evaluate potential insights into the pathogenesis of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) using multimodal diagnostic imaging and laboratory evaluation in long-term follow-up. A retrospective, single-center case series was conducted on seven consecutive patients (14 eyes) who were given a diagnosis of APMPPE from March 1, 2011, through June 30, 2019 with at least three months of follow-up. Clinical characteristics (age, symptoms, visual acuity [VA]), laboratory testing including coxsackievirus titers, and multimodal imaging from fundus photography, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), fluorescein angiography (FA), and indocyanine green angiography (ICG) were analyzed for each patient. The initial median VA was 20/71 and final median VA was 20/22. Coxsackievirus B (CVB) titers were elevated (≥ 1:80) in six of seven patients, with a four-fold increase in convalescent titers seen in two patients suggestive of recent infection. All patients were treated with oral corticosteroids, and five patients underwent corticosteroid-sparing immunomodulatory therapy. Initially, multifocal deep choroidal lesions were observed in the posterior pole corresponding to patches of hypocyanescence on ICG. Overlying retinal pigment epithelium (RPE) disease was observed on FAF, although this finding was not universally observed, suggesting that RPE disease may occur as a sequelae to unchecked choroidal inflammation. SD-OCT architectural changes confirmed outer retina and ellipsoid zone disruption. FA of active lesions showed early hypofluorescence and late hyperfluorescence with surrounding leakage while inactive disease showed areas of staining. Long-term follow-up of multimodal diagnostic imaging in APMPPE revealed that choroidal inflammation likely precedes RPE change and photoreceptor damage. Elevation of coxsackievirus titers with seroconversion may be associated with an infectious trigger in concert with immune-mediated disease in this posterior uveitis syndrome., Competing Interests: The authors have declared that no competing interests exist.

Objective: To test the hypothesis that neuroinflammation is a key process in adult Niemann-Pick type C (NPC) disease, we undertook PET scanning utilizing a ligand binding activated microglia on 9 patients and 9 age- and sex-matched controls., Method: We scanned all participants with the PET radioligand 11 C-(R)-PK-11195 and undertook structural MRI to measure gray matter volume and white matter fractional anisotropy (FA)., Results: We found increased binding of 11 C-(R)-PK-11195 in total white matter compared to controls ( p < 0.01), but not in gray matter regions, and this did not correlate with illness severity or duration. Gray matter was reduced in the thalamus ( p < 0.0001) in patients, who also showed widespread reductions in FA across the brain compared to controls ( p < 0.001). A significant correlation between 11 C-(R)-PK11195 binding and FA was shown ( p = 0.002), driven by the NPC patient group., Conclusions: Our findings suggest that neuroinflammation-particularly in white matter-may underpin some structural and degenerative changes in patients with NPC., (© 2020 American Academy of Neurology.)

HIV infection can result in vision loss from different causes, including HIV retinopathy and uveitis secondary to other infections, such as toxoplasmosis and viral retinitis. It is imperative to identify any infectious causes of uveitis to successfully treat the condition and prevent further vision loss. Metagenomic deep sequencing (MDS) is an emerging technology that presents an unbiased approach to the evaluation of clinical syndromes, including uveitis, that have not been diagnosed by pathogen-specific testing. Herein we present a case of a woman living with HIV with 11 years of relapsing bilateral uveitis refractory to systemic corticosteroid therapy who was diagnosed with human T-lymphotropic virus type 1 (HTLV-1)-associated uveitis by this technology. We also briefly review the literature of MDS as a diagnostic tool and the epidemiology, pathogenesis, and diagnosis of HTLV-1-associated uveitis., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is a rare autoimmune condition that typically presents as progressive uveitis and vitreoretinal degeneration between the second and third decades of life. Though traditionally attributed to inherited mutations of the CAPN5 gene, few reports of de novo variants exist. This report of vision and hearing loss in a 3 year-old girl describes the youngest documented case of ADNIV due to a de novo pathogenic c.865C>T (p.Arg289Trp) CAPN5 variant, illustrating the early stages of this enigmatic disease process.

Objectives: Secondhand smoke (SHS) and other air pollutants adversely affect the health of pregnant women and infants. A feasibility study aimed at reducing air pollution in homes of pregnant women or infants living with a smoker was completed., Methods: In collaboration with the Baltimore City Health Department, women ≥ 18 years of age and either pregnant nonsmokers, or post-partum (any smoking status) with an infant age 0-12 months were recruited. Homes had at least one smoker. Intervention included two air purifiers and secondhand smoke education. Outcomes included feasibility, change in fine particulate matter (PM 2.5 ), air nicotine, and salivary cotinine pre- and post-intervention., Results: Fifty women were enrolled (mean age 27 years, 92% African American, 71% single, 94% Medicaid eligible, 34% reported smoking) and 86% completed the study. Of the 50 women, 32 had infants and 18 were pregnant at time of enrollment. Post- intervention, 70% of participants reported smokers were less likely to smoke indoors, and 77% had at least one air purifier turned on at the final visit. Participant satisfaction was high (91%) and 98% would recommend air purifiers. Indoor PM 2.5 was significantly decreased (P < 0.001). Salivary cotinine was significantly decreased for non-smoking women (P < 0.01) but not infants, and no significant change in air nicotine occurred (P = 0.6)., Conclusions: Air purifiers with SHS education is a feasible intervention in homes of women and infants. These data demonstrate reduction in indoor PM 2.5 and salivary cotinine in non-smoking adults. Air purifiers are not an alternative for smoking cessation and a home/ car smoking ban. Smoking cessation should be strongly encouraged for all pregnant women, and nonsmoking mothers with infants should be counseled to completely avoid SHS exposure. This study provides support for a future intervention evaluating clinical endpoints., (Copyright © 2017. Published by Elsevier Inc.)

Background: We report results of the novel Washout Allometric Reference Method (WARM) that uses estimates of cerebral blood flow and amyloid load from the same [ 11 C]Pittsburgh Compound B ([ 11 C]PiB) retention maps in brain to distinguish between patients with different forms dementia, including Alzheimer's disease, and healthy volunteers. The method introduces two approaches to the identification of brain pathology related to amyloid accumulation, (1) a novel analysis of amyloid binding based on the late washout of the tracer from brain tissue, and (2) the simultaneous estimation of absolute cerebral blood flow indices (sCBF) from the early accumulation of the tracer in brain tissue. Objective: We tested the hypothesis that a change of cerebral blood flow is correlated with the degree of tracer [ 11 C]PiB retention, reflecting dendritic spine pathology and consequent inhibition of brain energy metabolism and reduction of blood flow by neurovascular coupling in neurodegenerative disorders, including Alzheimer's disease. Methods: Previously reported images of [ 11 C]PiB retention in brain of 29 subjects with cognitive impairment or dementia [16 Alzheimer's Disease (AD), eight subjects with dementia with Lewy bodies (DLB), five patients with frontotemporal lobar degeneration (FTLD), five patients with mild cognitive impairment, and 29 age-matched healthy control subjects (HC)], underwent analysis of PiB delivery and retention by means of WARM for quantitation of [ 11 C]PiB's binding potentials ( BP ND ) and correlated surrogate cerebral blood flow (sCBF) estimates, based on the [ 11 C]PiB images, compared to estimates by conventional Standard Uptake Value Ratio (SUVR) of [ 11 C]PiB retention with cerebellum gray matter as reference. Receiver Operating Characteristics (ROC) revealed the power of discrimination among estimates. Results: For AD, the discriminatory power of [ 11 C]PiB binding potential ( BP ND ) by WARM exceeded the power of SUVR that in turn exceeded the power of sCBF estimates. Differences of [ 11 C]PiB binding and sCBF measures between AD and HC both were highly significant ( p < 0.001). For all the dementia groups as a whole, sCBF estimates revealed the greatest discrimination between the patient and HC groups. WARM resolves a major issue of amyloid load quantification with [ 11 C]PiB in human brain by determining absolute sCBF and amyloid load measures from the same images. The two parameter approach provides key discriminary information in AD for which [ 11 C]PiB traditionally is used, as well as for the distinct flow deficits in FTLD, and the marked parietal and occipital lobe flow deficits in DLB. Conclusion: We conclude that WARM yields estimates of two important variables that together discriminate among patients with dementia, including AD, and healthy volunteers, with ROC that are superior to conventional methods of analysis. The distinction between estimates of flow and amyloid load from the same dynamic emission tomograms provides valuable pathogenetic information.

Introduction: The concept of the "Golden Hour" has been a time-honored tenet of prehospital trauma care, despite a paucity of data to substantiate its validity. Non-compressible torso hemorrhage has been demonstrated to be a significant cause of mortality in both military and civilian settings. We sought to characterize the impact of prehospital time and torso injury severity on survival. Furthermore, we hypothesized that time would be a significant determinant of mortality in patients with higher Abbreviated Injury Scale (AIS) grades of torso injury (AIS ≥ 4) and field hypotension (prehospital SBP ≤ 110 mmHg) as these injuries are commonly associated with hemorrhage., Methods: Data for this analysis was generated from a registry of 2,523,394 injured patients entered into the National Trauma Data Bank Research Data Set from 2012 to 2014. Patients with torso injury were identified utilizing Abbreviated Injury Scale (AIS) for body regions 4 (Thorax) and 5 (Abdomen). Specific inclusion criteria for this study included pre-hospital time, prehospital SBP ≤110 mmHg, torso injury qualified by AIS and mortality. Patients with non-survivable torso injury (AIS = 6), severe head injuries (AIS ≥ 3), no signs of life in the field (SBP = 0), interfacility transfers, or those with any missing data elements were excluded. This classification methodology identified a composite cohort of 42,135 adult patients for analysis., Results: The overall mortality rate of the study population was 7.9% (3326/42,135); Torso AIS and prehospital time were noted to be strong independent predictors of patient mortality in all population strata of the analysis (P < 0.05). The data demonstrated a profound incremental increase in mortality in the early time course after injury associated with torso AIS ≥4., Conclusion: In patients with high-grade torso injury, AIS grades ≥4, the degree anatomic disruption is associated with significant hemorrhage. In our study, a precipitous rise in patient mortality was exhibited in this high-grade injury group at prehospital times <30 min. Our data highlight the critical nature of prehospital time in patients with non-compressible torso hemorrhage. However, realizing that evacuation times ≤30 min may not be realistic, particularly in rural or austere environments, future efforts should be directed toward the development of therapies to increase the window of survival in the prehospital environment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Multidisciplinary nutrition teams can help guide the use of parenteral nutrition (PN), thereby reducing infectious risk, morbidity, and associated costs. Starting in 2007 at Harborview Medical Center, weekly multidisciplinary meetings were established to review all patients receiving PN. This study reports on observed changes in utilization from 2005-2010., Materials and Methods: All patients who received PN from 2005-2010 were followed prospectively. Clinical data and PN utilization data were recorded. Patients were grouped into cohorts based on exposure to weekly multidisciplinary nutrition team meetings (from 2005-2007 and from 2008-2010). Patients were also stratified by location, primary service, and ultimate disposition., Results: In total, 794 patients were included. After initiation of multidisciplinary nutrition meetings, the rate of patients who started PN decreased by 27% (relative risk [RR], 0.73; 95% confidence interval [CI], 0.63-0.84). A reduction in the number of patients receiving PN was observed in both the intensive care unit (ICU) and on the acute care floor (RR, 0.64; 95% CI, 0.53-0.77 and RR, 0.80; 95% CI, 0.64-0.99, respectively). The rate of patients with short-duration PN use (PN duration of <5 days) declined by 30% in the ICU (RR, 0.70; 95% CI, 0.51-0.97) and by 27% on acute care floors (RR, 0.73; 95% CI, 0.51-1.03)., Conclusions: Weekly multidisciplinary review of patients receiving PN was associated with reductions in the number of patients started on PN, total days that patients received PN, and number of patients who had short-duration (<5 days) PN use., (© 2015 American Society for Parenteral and Enteral Nutrition.)

Angiogenesis and epidermal growth factor receptor (EGFR) inhibition has been shown to have anti-tumour efficacy, and enhance the therapeutic effects of cytotoxic chemotherapy in metastatic colorectal cancer. The interplay of signalling alterations and changes in metabolism and hypoxia in tumours following anti-VEGF and anti-EGFR treatment is not well understood. We aimed to explore the pharmacodynamics of cetuximab and bevacizumab treatment in human colon carcinoma tumour cells in vitro and xenograft models through proteomic profiling, molecular imaging of metabolism and hypoxia, and evaluation of therapy-induced changes in tumour cells and the tumour microenvironment. Both cetuximab and bevacizumab inhibited tumour growth in vivo, and this effect was associated with selectively perturbed glucose metabolism and reduced hypoxic volumes based on PET/MRI imaging. Global proteomic profiling of xenograft tumours (in presence of cetuximab, bevacizumab, and combination treatments) revealed alterations in proteins involved in glucose, lipid and fatty acid metabolism (e.g., GPD2, ATP5B, STAT3, FASN), as well as hypoxic regulators and vasculogenesis (e.g., ATP5B, THBS1, HSPG2). These findings correlated with western immunoblotting (xenograft lysates) and histological examination by immunohistochemistry. These results define important mechanistic insight into the dynamic changes in metabolic and hypoxic response pathways in colorectal tumours following treatment with cetuximab and bevacizumab, and highlight the ability of these therapies to selectively impact on tumour cells and extracellular microenvironment.