Purpose: To assess retinal function in young patients with X-linked juvenile retinoschisis (XLRS), a disorder that is known to alter ERG postreceptor retinal components and also possibly photoreceptor components. Methods: ERG responses to full-field stimuli were recorded under scotopic and photopic conditions in 12 XLRS patients aged 1 to 15 (median 8) years. A- and b-wave amplitudes and implicit times were examined over a range of stimulus intensities. Rod and cone photoreceptor (SROD, RROD, SCONE, RCONE) and rod-driven postreceptor (log σ, VMAX) response parameters were calculated from the a- and b-waves. Data from XLRS patients were evaluated for significant change with age. Results: A- and b-wave amplitudes were smaller in XLRS patients compared with controls under both scotopic and photopic conditions. Saturated photoresponse amplitude (RROD), postreceptor b-wave (log σ), and saturated b-wave amplitude (VMAX) were significantly lower in XLRS patients than in controls; SROD did not differ between the two groups. SCONE and RCONE values were normal. In XLRS patients, neither a- and b-wave amplitudes nor calculated parameters (SROD, RROD, log σ, VMAX,SCONE, and RCONE) changed with age. Conclusions: In these young XLRS patients, RROD and a-wave amplitudes were significantly smaller than in controls. Thus, in addition to XLRS causing postreceptor dysfunction, an effect of XLRS on rod photoreceptors cannot be ignored.
PURPOSE OF REVIEW: In recent years, literature on neuroinflammatory disorders has dramatically expanded, as have options for treatment. However, few reviews have focused on skull-based manifestations of inflammatory disorders. RECENT FINDINGS: Here, we review the clinical manifestations, etiologies, diagnostic workup, and treatment of both systemic and localized inflammatory diseases of the skull base with a focus on recent updates to the literature. This review aims to guide the workup and management of this complex set of diseases.
PRéCIS:: Neuroretinal rim minimum distance band (MDB) thickness is significantly lower in older subjects and African Americans compared with whites. It is similar in both sexes. PURPOSE: To evaluate the relationship between age, race, and sex with the neuroretinal rim using high-density spectral-domain optical coherence tomography optic nerve volume scans of normal eyes. METHODS: A total of 256 normal subjects underwent Spectralis spectral-domain optical coherence tomography optic nerve head volume scans. One eye was randomly selected and analyzed for each subject. Using custom-designed software, the neuroretinal rim MDB thickness was calculated from volume scans, and global and quadrant neuroretinal rim thickness values were determined. The MDB is a 3-dimensional neuroretinal rim band comprised of the shortest distance between the internal limiting membrane and the termination of the retinal pigment epithelium/Bruch's membrane complex. Multiple linear regression analysis was performed to determine the associations of age, race, and sex with neuroretinal rim MDB measurements. RESULTS: The population was 57% female and 69% white with a mean age of 58.4±15.3 years. The mean MDB thickness in the normal population was 278.4±47.5 µm. For this normal population, MDB thickness decreased by 0.84 µm annually (P<0.001). African Americans had thinner MDBs compared with whites (P=0.003). Males and females had similar MDB thickness values (P=0.349). CONCLUSION: Neuroretinal rim MDB thickness measurements decreased significantly with age. African Americans had thinner MDB neuroretinal rims than whites.
Arboleda-Velasquez JF, Lopera F, O'Hare M, Delgado-Tirado S, Marino C, Chmielewska N, Saez-Torres KL, Amarnani D, Schultz AP, Sperling RA, Leyton-Cifuentes D, Chen K, Baena A, Aguillon D, Rios-Romenets S, Giraldo M, Guzmán-Vélez E, Norton DJ, Pardilla-Delgado E, Artola A, Sanchez JS, Acosta-Uribe J, Lalli M, Kosik KS, Huentelman MJ, Zetterberg H, Blennow K, Reiman RA, Luo J, Chen Y, Thiyyagura P, Su Y, Jun GR, Naymik M, Gai X, Bootwalla M, Ji J, Shen L, Miller JB, Kim LA, Tariot PN, Johnson KA, Reiman EM, Quiroz YT. Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report. Nat Med 2019;25(11):1680-1683.Abstract
We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease.
The gene is the first described human tumor suppressor gene and plays an integral role in the development of retinoblastoma, a pediatric malignancy of the eye. Since its discovery, the stepwise characterization and cloning of have laid the foundation for numerous advances in the understanding of tumor suppressor genes, retinoblastoma tumorigenesis, and inheritance. Knowledge of led to a paradigm shift in the field of cancer genetics, including widespread acceptance of the concept of tumor suppressor genes, and has provided crucial diagnostic and prognostic information through genetic testing for patients affected by retinoblastoma. This article reviews the long history of gene research, characterization, and cloning, and also discusses recent advances in retinoblastoma genetics that have grown out of this foundational work.
PURPOSE: To evaluate the defocus curves of 4 presbyopia-correcting intraocular lenses (IOLs). SETTING: Department of Ophthalmology, Goethe University, Frankfurt, Germany. DESIGN: Prospective case series. METHODS: Patients included in the study had bilateral surgery with implantation of diffractive panfocal, diffractive trifocal, segmental refractive (SegRef), or extended-depth-of-focus (EDOF) presbyopia-correcting IOLs. The uncorrected (UDVA) and corrected (CDVA) distance visual acuities, uncorrected intermediate and near visual acuities, distance-corrected intermediate (DCIVA) and near (DCNVA) visual acuities, defocus curve, and spectacle independence were measured. RESULTS: The UDVA and CDVA were not significantly different between groups (P > .05); however, the EDOF group had worse near CDVA (P < .001). The trifocal and EDOF groups showed better DCIVA than the panfocal and SegRef group at 80 cm (P < .001); the EDOF and panfocal groups had comparable DCIVA at 60 cm (P > .05). Defocus curves showed no significant between-group differences from 4 m to 2 m (P > .05). The EDOF group had better visual acuity from 1 m to 67 cm than the trifocal and SegRef groups and better visual acuity than the panfocal group at 1 m (P > .05). Compared with the other IOLs, the panfocal IOL yielded significantly better visual acuity at 50 cm (P < .001) and the EDOF IOL worse visual acuity at 40 cm (P < .01). There was a significant difference in spectacle independence between the panfocal group and EDOF group (P < .05) but no difference between the other groups. CONCLUSIONS: The 4 IOLs provided equally good CDVA. The EDOF IOL yielded slightly better DCIVA but worse DCNVA than the other IOLs. Only the panfocal IOL gave better DCIVA at 50 cm.
PURPOSE OF REVIEW: Optic neuritis is an autoimmune optic neuropathy that has been associated with multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and more recently antimyelin oligodendrocyte glycoprotein (anti-MOG)-positive disorder. At initial presentation, it is often difficult to differentiate these entities given their significant overlap in clinical presentation and MRI findings. This review summarizes the distinguishing clinical and radiological features of MS, NMOSD, and anti-MOG disorders to help clinicians accurately diagnose and manage patients affected by these conditions. RECENT FINDINGS: Antiaquaporin-4 (AQP4) and more recently anti-MOG antibodies are both associated with central nervous system demyelinating diseases that often initially present with optic neuritis. Serologic testing now allows for a new classification of these overlapping conditions that can help to differentiate 'typical' optic neuritis that is often associated with MS from 'atypical' optic neuritis associated with NMOSD and anti-MOG-positive disorder. SUMMARY: Optic neuritis associated with MS, NMOSD, and anti-MOG-positive disease can have a similar clinical presentation. However, some clinical and radiologic findings can help clinicians to differentiate these entities so that they can be properly managed to optimize visual prognosis.
PURPOSE: To investigate the association between choroidal thickness and persistent subretinal fluid (PSF) after surgery for recent-onset rhegmatogenous retinal detachment (RRD). DESIGN: Case-control study. PARTICIPANTS: Fourteen eyes with macula-off RRD (with fovea on and off) that achieved retinal reattachment on funduscopy and demonstrated PSF after surgery (PSF group) were compared with 62 eyes with macula-off RRD (with fovea on and off) that did not demonstrate PSF after surgery (non-PSF group). METHODS: The diagnosis of PSF was made by the detection of subretinal fluid pockets on OCT beyond 6 weeks after surgery. Covariates included baseline demographics, duration of RRD, area of RRD, foveal status, method of subretinal fluid drainage, retinal pigment epithelium (RPE) changes, and choroidal thickness in both eyes. Multivariate regression analysis was performed by adding gender, age, and pathologic myopia into the model. The secondary outcomes included postoperative vision and time to resolution of PSF. MAIN OUTCOME MEASURES: Subfoveal choroidal thickness in affected eyes, measured by enhanced depth imaging OCT images. RESULTS: The percentage of eyes that underwent vitrectomy, scleral buckle surgery, and pneumatic retinopexy were 71.4%, 14.3%, and 14.3% in the PSF group, respectively, and 87.1%, 11.3%, and 1.6% in the non-PSF group, respectively. Eyes with PSF showed significantly thicker subfoveal choroid than eyes without PSF (305±61 μm vs. 200±70 μm, respectively; adjusted difference, 78.6±19.1 μm; 95% confidence interval [CI], 40.3-116.8 μm; P < 0.001). The PSF group demonstrated a greater proportion of RPE changes in fellow eyes (30.8% vs. 1.7%; P = 0.03) and significantly worse best-corrected visual acuity at the 12-month follow-up (P = 0.03). Multiple logistic regression analysis revealed that choroidal thickness of 280 μm or more was a significant factor associated with the presence of PSF (adjusted odds ratio [AOR], 13.4; 95% CI, 3.1-34.7 [P = 0.001]. CONCLUSIONS: Persistent subretinal fluid is associated with increased subfoveal choroidal thickness in surgical and fellow eyes and with RPE changes in the fellow eye. This indicates that PSF likely belongs to the pachychoroid spectrum. In affected eyes, PSF tends to persist for more than 1 year and results in delayed visual recovery.
of in of Consortium GGPAD (GGLAD), Hauser MA, Allingham RR, Aung T, Van Der Heide CJ, Taylor KD, Rotter JI, Wang S-HJ, Bonnemaijer PWM, Williams SE, Abdullahi SM, Abu-Amero KK, Anderson MG, Akafo S, Alhassan MB, Asimadu I, Ayyagari R, Bakayoko S, Nyamsi PB, Bowden DW, Bromley WC, Budenz DL, Carmichael TR, Challa P, Chen Y-DI, Chuka-Okosa CM, Cooke Bailey JN, Costa VP, Cruz DA, DuBiner H, Ervin JF, Feldman RM, Flamme-Wiese M, Gaasterland DE, Garnai SJ, Girkin CA, Guirou N, Guo X, Haines JL, Hammond CJ, Herndon L, Hoffmann TJ, Hulette CM, Hydara A, Igo RP, Jorgenson E, Kabwe J, Kilangalanga NJ, Kizor-Akaraiwe N, Kuchtey RW, Lamari H, Li Z, Liebmann JM, Liu Y, Loos RJF, Melo MB, Moroi SE, Msosa JM, Mullins RF, Nadkarni G, Napo A, Ng MCY, Nunes HF, Obeng-Nyarkoh E, Okeke A, Okeke S, Olaniyi O, Olawoye O, Oliveira MB, Pasquale LR, Perez-Grossmann RA, Pericak-Vance MA, Qin X, Ramsay M, Resnikoff S, Richards JE, Schimiti RB, Sim KS, Sponsel WE, Svidnicki PV, Thiadens AAHJ, Uche NJ, van Duijn CM, de Vasconcellos JPC, Wiggs JL, Zangwill LM, Risch N, Milea D, Ashaye A, Klaver CCW, Weinreb RN, Ashley Koch AE, Fingert JH, Khor CC. Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry. JAMA 2019;322(17):1682-1691.Abstract
Importance: Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives: To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants: A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures: Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures: Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results: A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance: In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies.
PURPOSE OF REVIEW: Impaired eye movements are frequently seen in ophthalmic and neurologic clinical practice, especially in individuals with movement disorders. Identification of the abnormal movement can aid initial diagnosis and improve understanding of the underlying disease pathophysiology. The present article reviews the ocular motor manifestations and recent research on them in common movement disorders. RECENT FINDINGS: Ocular motor manifestations and their pathophysiologic correlates are being defined. In particular, study of eye movements can help clarify the changing clinicopathologic spectrum of atypical parkinsonian disorders. The pathophysiology and natural history of blepharospasm are being elucidated. Recent research focuses on high-resolution imaging and other technological advances to improve the sensitivity of the ocular motility exam. Eye movements are being studied as biomarkers for diagnosis and progression in clinical care and trials. SUMMARY: The current review summarizes ocular motor manifestations in common movement disorders, and presents recent research investigating their cause and treatment.
Purpose: To analyze imaging artifacts and segmentation errors with wide-field swept-source optical coherence tomography angiography (SS-OCTA) in diabetic retinopathy (DR). Methods: We conducted a prospective, observational study at Massachusetts Eye and Ear from December 2018 to March 2019. Proliferative diabetic retinopathy (PDR), nonproliferative diabetic retinopathy (NPDR), diabetic patients with no diabetic retinopathy (DR), and healthy control eyes were included. All patients were imaged with a SS-OCTA and the Montage Angio (15 × 9 mm) was used for analysis. Images were independently evaluated by two graders using the motion artifact score (MAS). All statistical analyses were performed using SPSS 25.0 and R software. Results: One hundred thirty-six eyes in 98 participants with the montage image were included in the study. Patients with more severe stages of DR had higher MAS by trend test analysis ( < 0.05). The occurrence of segmentation error was 0% in the healthy group, 10.53% in the no DR group, 10.00% in the NPDR group, and 50% in the PDR group. Multivariate regression analysis showed that the severity of DR and dry eye were the major factors affecting MAS ( < 0.05). There were some modifiable artifacts that could be corrected to improve image quality. Conclusions: Wide field SS-OCTA assesses retinal microvascular changes by noninvasive techniques, yet distinguishing real alterations from artifacts is paramount to accurate interpretations. DR severity and dry eye correlated with MAS. Translational Relevance: Understanding contributing factors and methods to reduce artifacts is critical to routine use and clinical trial with wide-field SS-OCTA.
PURPOSE OF REVIEW: The phakomatoses are a group of inherited disorders with variable clinical manifestations that are characterized by brain, cutaneous, ocular and other distinct lesions in multiple organs. Correctly recognizing the neuro-ophthalmic signs and symptoms can lead to early diagnosis and treatment. The group is composed of neurofibromatosis (type 1 and 2), tuberous sclerosis complex, von Hippel-Lindau, ataxia-telangiectasia and Sturge-Weber syndromes. However, more than 60 syndromes have been described in the medical literature. This review provides an update on the diagnosis and management of phakomatoses with a focus on their clinical neuro-ophthalmic manifestations. RECENT FINDINGS: Phakomatoses are a group of inherited syndromes with variable clinical manifestations that are characterized by brain, cutaneous, ocular and other distinct lesions in multiple organs. Recent advances in diagnostic and treatment options that have contributed to prompt recognition and management of these disorders are discussed with an emphasis on the beneficial effects on vision. SUMMARY: Phakomatoses, also known as neuro-oculo-cutaneous syndromes, are inherited disorders with characteristic lesions in multiple organs. Because of their frequent ocular involvement thorough ophthalmologic and neuro-ophthalmic evaluation is critical in this patient population in order to prevent vision loss and life-threatening complications that are often associated with these disorders.
PURPOSE OF REVIEW: Immune checkpoint inhibitors are currently an exceedingly powerful tool in the management of hitherto incurable malignancies and their use in clinical practice is expected to increase in the near future. The purpose of this review is to discuss the current medical uses of checkpoint inhibitors with a focus on their neuro-ophthalmic side-effects. RECENT FINDINGS: Immune checkpoint inhibitors have emerged as a promising breakthrough in the treatment of several tumor types. However, these targeted therapies can induce a wide range of immune-related ophthalmic and neuro-ophthalmic toxicities. It is important for neuro-ophthamologists to promptly recognize and manage these adverse events that can potentially threaten vision. SUMMARY: There are currently seven FDA-approved immune checkpoint inhibitors and several ones are under investigation. In general, immunotherapy is considered a well tolerated, safe and efficacious treatment option for many cancer patients. Nevertheless, because of their unique mechanism of action, these molecules can alter the immune response and result in immune-related adverse effects in almost every organ with an estimated incidence of ophthalmic side effects in this patient population of less than 1%.
Enterococci are unusually well adapted for survival and persistence in a variety of adverse environments, including on inanimate surfaces in the hospital environment and at sites of infection. This intrinsic ruggedness undoubtedly played a role in providing opportunities for enterococci to interact with other overtly drug-resistant microbes and acquire additional resistances on mobile elements. The rapid rise of antimicrobial resistance among hospital-adapted enterococci has rendered hospital-acquired infections a leading therapeutic challenge. With about a quarter of a genome of additional DNA conveyed by mobile elements, there are undoubtedly many more properties that have been acquired that help enterococci persist and spread in the hospital setting and cause diseases that have yet to be defined. Much remains to be learned about these ancient and rugged microbes, particularly in the area of pathogenic mechanisms involved with human diseases.
PURPOSE OF REVIEW: To summarize recent advances in the diagnosis of giant cell arteritis (GCA). RECENT FINDINGS: Less common manifestations of GCA include corneal edema, proptosis from lacrimal gland ischemia and sensorineuronal hearing loss. Histology studies have suggested that temporal artery biopsies (TAB) with fixed specimen lengths of 15 mm may be adequate to prevent false negative biopsies. In centers with appropriate radiologic expertise, a European rheumatology consensus guideline has proposed Doppler ultrasound as a first-line confirmatory test for GCA in lieu of temporal artery biopsy. Finding extracranial large vessel disease can help to diagnose GCA. Statistical prediction rules can help risk stratify patients with suspected GCA. Age and platelet level when maintained as continuous variables are the strongest predictors for GCA. SUMMARY: GCA can present with diverse ophthalmic and systemic presentations and expedient recognition of same can avoid diagnostic delay and possible vision loss, among other complications. TAB remains the conventional diagnostic standard test for GCA. The use of statistical prediction models and increased expertise in noninvasive imaging techniques such as ultrasound may decrease reliance on TAB, especially in patients determined to be at low risk for GCA.
Importance: The incidence of dry eye disease has increased; the potential for crowdsource data to help identify undiagnosed dry eye in symptomatic individuals remains unknown. Objective: To assess the characteristics and risk factors associated with diagnosed and undiagnosed symptomatic dry eye using the smartphone app DryEyeRhythm. Design, Setting, and Participants: A cross-sectional study using crowdsourced data was conducted including individuals in Japan who downloaded DryEyeRhythm and completed the entire questionnaire; duplicate users were excluded. DryEyeRhythm was released on November 2, 2016; the study was conducted from November 2, 2016, to January 12, 2018. Exposures: DryEyeRhythm data were collected on demographics, medical history, lifestyle, subjective symptoms, and disease-specific symptoms, using the Ocular Surface Disease Index (100-point scale; scores 0-12 indicate normal, healthy eyes; 13-22, mild dry eye; 23-32, moderate dry eye; 33-100, severe dry eye symptoms), and the Zung Self-Rating Depression Scale (total of 20 items, total score ranging from 20-80, with ≥40 highly suggestive of depression). Main Outcomes and Measures: Multivariate-adjusted logistic regression analysis was used to identify risk factors for symptomatic dry eye and to identify risk factors for undiagnosed symptomatic dry eye. Results: A total of 21 394 records were identified in our database; 4454 users, included 899 participants (27.3%) with diagnosed and 2395 participants (72.7%) with undiagnosed symptomatic dry eye, completed all questionnaires and their data were analyzed. A total of 2972 participants (66.7%) were women; mean (SD) age was 27.9 (12.6) years. The identified risk factors for symptomatic vs no symptomatic dry eye included younger age (odds ratio [OR], 0.99; 95% CI, 0.987-0.999, P = .02), female sex (OR, 1.99; 95% CI, 1.61-2.46; P < .001), pollinosis (termed hay fever on the questionnaire) (OR, 1.35; 95% CI, 1.18-1.55; P < .001), depression (OR, 1.78; 95% CI, 1.18-2.69; P = .006), mental illnesses other than depression or schizophrenia (OR, 1.87; 95% CI, 1.24-2.82; P = .003), current contact lens use (OR, 1.27; 95% CI, 1.09-1.48; P = .002), extended screen exposure (OR, 1.55; 95% CI, 1.25-1.91; P < .001), and smoking (OR, 1.65; 95% CI, 1.37-1.98; P < .001). The risk factors for undiagnosed vs diagnosed symptomatic dry eye included younger age (OR, 0.96; 95% CI, 0.95-0.97; P < .001), male sex (OR, 0.55; 95% CI, 0.42-0.72; P < .001), as well as absence of collagen disease (OR, 95% CI, 0.23; 0.09-0.60; P = .003), mental illnesses other than depression or schizophrenia (OR, 0.50; 95% CI, 0.36-0.69; P < .001), ophthalmic surgery other than cataract surgery and laser-assisted in situ keratomileusis (OR, 0.41; 95% CI, 0.27-0.64; P < .001), and current (OR, 0.64; 95% CI, 0.54-0.77; P < .001) or past (OR, 0.45; 95% CI, 0.34-0.58; P < .001) contact lens use. Conclusions and Relevance: This study's findings suggest that crowdsourced research identified individuals with diagnosed and undiagnosed symptomatic dry eye and the associated risk factors. These findings could play a role in earlier prevention or more effective interventions for dry eye disease.
OBJECTIVE: Steady state insulin-like growth factor-1 (IGF-1) levels vary significantly during continuous intravenous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) in the first weeks of life in extremely preterm infants. We evaluated interleukin-6 (IL-6) and insulin-like growth factor binding protein-1 (IGFBP-1) levels as predictors of low IGF-1 levels. METHODS: Nineteen extremely preterm infants were enrolled in a trial, 9 received rhIGF-1/rhIGFBP-3 and 10 received standard neonatal care. Blood samples were analyzed daily for IGF-1, IL-6 and IGFBP-1 during intervention with rhIGF-1/rhIGFBP-3. RESULTS: Thirty seven percent of IGF-1 values during active treatment were <20 μg/L. Among treated infants, higher levels of IL-6, one and two days before sampled IGF-1, were associated with IGF-1 < 20 μg/L, gestational age adjusted OR 1.30 (95% CI 1.03-1.63), p = .026, and 1.57 (95% CI 1.26-1.97), p < .001 respectively. Higher levels of IGFBP-1 one day before sampled IGF-1 was also associated with IGF-1 < 20 μg/L, gestational age adjusted OR 1.74 (95% CI 1.19-2.53), p = .004. CONCLUSION: In preterm infants receiving continuous infusion of rhIGF-1/rhIGFBP-3, higher levels of IL-6 and IGFBP-1 preceded lower levels of circulating IGF-1. These findings demonstrate a need to further evaluate if inflammation and/or infection suppress serum IGF-1 levels. The trial is registered at ClinicalTrials.gov (NCT01096784).
Industrial farms are unique, human-created ecosystems that provide the perfect setting for the development and dissemination of antibiotic resistance. Agricultural antibiotic use amplifies naturally occurring resistance mechanisms from soil ecologies, promoting their spread and sharing with other bacteria, including those poised to become endemic within hospital environments. To better understand the role of enterococci in the movement of antibiotic resistance from farm to table to clinic, we characterized over 300 isolates of cultured from raw chicken meat purchased at U.S. supermarkets by the Consumers Union in 2013. and were the predominant species found, and antimicrobial susceptibility testing uncovered striking levels of resistance to medically important antibiotic classes, particularly from classes approved by the FDA for use in animal production. While nearly all isolates were resistant to at least one drug, bacteria from meat labeled as raised without antibiotics had fewer resistances, particularly for Whole-genome sequencing of 92 isolates revealed that both commensal- and clinical-isolate-like enterococcal strains were associated with chicken meat, including isolates bearing important resistance-conferring elements and virulence factors. The ability of enterococci to persist in the food system positions them as vehicles to move resistance genes from the industrial farm ecosystem into more human-proximal ecologies. Bacteria that contaminate food can serve as a conduit for moving drug resistance genes from farm to table to clinic. Our results show that chicken meat-associated isolates of are often multidrug resistant, closely related to pathogenic lineages, and harbor worrisome virulence factors. These drug-resistant agricultural isolates could thus represent important stepping stones in the evolution of enterococci into drug-resistant human pathogens. Although significant efforts have been made over the past few years to reduce the agricultural use of antibiotics, continued assessment of agricultural practices, including the roles of processing plants, shared breeding flocks, and probiotics as sources for resistance spread, is needed in order to slow the evolution of antibiotic resistance. Because antibiotic resistance is a global problem, global policies are needed to address this threat. Additional measures must be taken to mitigate the development and spread of antibiotic resistance elements from farms to clinics throughout the world.
C-fibers are unmyelinated nerve fibers that transmit high threshold mechanical, thermal, and chemical signals that are associated with pain sensations. This review examines current literature on measuring altered peripheral nerve morphology and discusses the most relevant aspects of corneal microscopy, especially whether corneal imaging presents significant method advantages over skin biopsy. Given its relative merits, corneal confocal microscopy would seem to be a more practical and patient-centric approach than utilizing skin biopsies.