Publications by authors named "David A Miller"

163 Publications

Expanding access to HIV services during the COVID-19 pandemic-Nigeria, 2020.

AIDS Res Ther 2021 09 19;18(1):62. Epub 2021 Sep 19.

Centers for Disease Control and Prevention, Division of Global HIV and TB, Center for Global Health, 1600 Clifton Road NE, Atlanta, GA, 30329, USA.

Background: To accelerate progress toward the UNAIDS 90-90-90 targets, US Centers for Disease Control and Prevention Nigeria country office (CDC Nigeria) initiated an Antiretroviral Treatment (ART) Surge in 2019 to identify and link 340,000 people living with HIV/AIDS (PLHIV) to ART. Coronavirus disease 2019 (COVID-19) threatened to interrupt ART Surge progress following the detection of the first case in Nigeria in February 2020. To overcome this disruption, CDC Nigeria designed and implemented adapted ART Surge strategies during February-September 2020.

Methods: Adapted ART Surge strategies focused on continuing expansion of HIV services while mitigating COVID-19 transmission. Key strategies included an intensified focus on community-based, rather than facility-based, HIV case-finding; immediate initiation of newly-diagnosed PLHIV on 3-month ART starter packs (first ART dispense of 3 months of ART); expansion of ART distribution through community refill sites; and broadened access to multi-month dispensing (MMD) (3-6 months ART) among PLHIV established in care. State-level weekly data reporting through an Excel-based dashboard and individual PLHIV-level data from the Nigeria National Data Repository facilitated program monitoring.

Results: During February-September 2020, the reported number of PLHIV initiating ART per month increased from 11,407 to 25,560, with the proportion found in the community increasing from 59 to 75%. The percentage of newly-identified PLHIV initiating ART with a 3-month ART starter pack increased from 60 to 98%. The percentage of on-time ART refill pick-ups increased from 89 to 100%. The percentage of PLHIV established in care receiving at least 3-month MMD increased from 77 to 93%. Among PLHIV initiating ART, 6-month retention increased from 74 to 92%.

Conclusions: A rapid and flexible HIV program response, focused on reducing facility-based interactions while ensuring delivery of lifesaving ART, was critical in overcoming COVID-19-related service disruptions to expand access to HIV services in Nigeria during the first eight months of the pandemic. High retention on ART among PLHIV initiating treatment indicates immediate MMD in this population may be a sustainable practice. HIV program infrastructure can be leveraged and adapted to respond to the COVID-19 pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12981-021-00385-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449993PMC
September 2021

In vivo imaging of the inner retinal layer structure in mice after eye-opening using visible-light optical coherence tomography.

Exp Eye Res 2021 Sep 4;211:108756. Epub 2021 Sep 4.

Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA. Electronic address:

The growth of the mouse eye and retina after birth is a dynamic, highly regulated process. In this study, we applied visible-light optical coherence tomography (vis-OCT), a non-invasive imaging technique, to examine developing retinal layer structures after eye-opening. We introduced a resampled circumpapillary B-scan averaging technique to improve the inter-layer contrast, enabling retinal layer thickness measurements as early as postnatal day 13 (P13) - right after eye-opening. We confirmed vis-OCT measurements using ex vivo confocal microscopy of retinal sections at different ages. Our results demonstrate that vis-OCT can visualize the developmental murine retinal layer structure in vivo, which offers us new opportunities to better characterize the pathological alterations in mouse models of developmental eye diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.exer.2021.108756DOI Listing
September 2021

Using interview surveys and multispecies occupancy models to inform vertebrate conservation.

Conserv Biol 2021 Sep 7. Epub 2021 Sep 7.

Nature Conservation Foundation, 3076/5, 4th Cross, Gokulam Park, Mysore, 570002, India.

Species distribution data are an essential biodiversity variable requiring robust monitoring to inform wildlife conservation. Yet, such data remain inherently sparse because of the logistical challenges of monitoring biodiversity across broad geographic extents. Surveys of knowledgeable members of the public (e.g., people from forest-dwelling communities) provide an opportunity to evaluate species distributions and the ecology of wildlife communities across large spatial scales. However, such data can be prone to both false negative (non-detection) and false positive (misidentification) errors, which may bias assessments of species distributions if uncorrected. Here we analyse detection histories from a large-scale interview survey for 30 vertebrate species across the Western Ghats biodiversity hotspot in India with a multispecies occupancy model that simultaneously corrects for non-detection and misidentification errors. Using this model, we integrate data across species for composite analyses on the responses of functional species groups (based on disturbance tolerance, diet and body mass traits) to spatial variation in environmental gradients, protection, and anthropogenic pressures. Our results highlight the importance of forest cover for species with low tolerance to human disturbance and the association of protected areas with higher occurrence for species across functional groups when compared with unprotected lands. Furthermore, we found the occurrence of species with low disturbance tolerance, herbivores and large-bodied species was limited by developmental pressures such as human settlements, and energy production and mining as well as demographic pressures such as biological resource extraction. Our work underscores the importance of maintaining forest cover and reducing deforestation within and outside protected areas for the conservation of threatened forest-dependent vertebrates. However, mitigating a suite of anthropogenic pressures is also critical for nature conservation in one of the world's most densely populated biodiversity hotspots. This article is protected by copyright. All rights reserved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cobi.13822DOI Listing
September 2021

Using interview surveys and multispecies occupancy models to inform vertebrate conservation.

Conserv Biol 2021 Sep 3. Epub 2021 Sep 3.

Nature Conservation Foundation, 3076/5, 4th Cross, Gokulam Park, 570002, India.

Species distribution data are an essential biodiversity variable requiring robust monitoring to inform wildlife conservation. Yet, such data remain inherently sparse because of the logistical challenges of monitoring biodiversity across broad geographic extents. Surveys of knowledgeable members of the public (e.g., people from forest-dwelling communities) provide an opportunity to evaluate species distributions and the ecology of wildlife communities across large spatial scales. However, such data can be prone to both false negative (non-detection) and false positive (misidentification) errors, which may bias assessments of species distributions if uncorrected. Here we analyse detection histories from a large-scale interview survey for 30 vertebrate species across the Western Ghats biodiversity hotspot in India with a multispecies occupancy model that simultaneously corrects for non-detection and misidentification errors. Using this model, we integrate data across species for composite analyses on the responses of functional species groups (based on disturbance tolerance, diet and body mass traits) to spatial variation in environmental gradients, protection, and anthropogenic pressures. Our results highlight the importance of forest cover for species with low tolerance to human disturbance and the association of protected areas with higher occurrence for species across functional groups when compared with unprotected lands. Furthermore, we found the occurrence of species with low disturbance tolerance, herbivores and large-bodied species was limited by developmental pressures such as human settlements, and energy production and mining as well as demographic pressures such as biological resource extraction. Our work underscores the importance of maintaining forest cover and reducing deforestation within and outside protected areas for the conservation of threatened forest-dependent vertebrates. However, mitigating a suite of anthropogenic pressures is also critical for nature conservation in one of the world's most densely populated biodiversity hotspots. This article is protected by copyright. All rights reserved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cobi.13832DOI Listing
September 2021

Myelopathy after traumatic lumbar vertebral intraosseous arteriovenous fistula with epidural venous drainage treated with transvenous embolization.

Clin Imaging 2021 Nov 8;79:341-344. Epub 2021 Aug 8.

Department of Diagnostic Radiology, Mayo Clinic, Jacksonville, FL, USA. Electronic address:

Spinal epidural arteriovenous fistulas are an uncommon entity. The authors present an interesting case of a 48-year-old man involved in a MVC five months prior to presenting with bilateral lower extremity weakness and hypoesthesia below the knees. MRI demonstrated a flow void in the L1 vertebral body burst fracture along with a dilated basivertebral vein draining in to engorged epidural venous plexus. Angiography confirmed an intraosseous arteriovenous fistula fed by T12 and L1arteries and epidural venous drainage. Complete obliteration by arterial embolization was precluded by origin of the artery of Adamkiewicz from the feeding L1 lumbar artery. Embolization using a transvenous approach allowed for successful obliteration of the fistula. Following the procedure, the patient had significant immediate improvement in the lower extremity symptoms. This is the first report of a posttraumatic spinal epidural arteriovenous fistula secondary to a vertebral burst fracture successfully treated by transvenous embolization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinimag.2021.08.001DOI Listing
November 2021

Outcomes and Surgical Considerations for Neurosurgical Patients Hospitalized with COVID-19-A Multicenter Case Series.

World Neurosurg 2021 Jul 6. Epub 2021 Jul 6.

Department of Neurological Surgery, Mayo Clinic, Jacksonville, Florida. Electronic address:

Objective: Neurosurgical patients are at a higher risk of having a severe course of coronavirus disease 2019 (COVID-19). The objective of this study was to determine morbidity, hospital course, and mortality of neurosurgical patients during the coronavirus disease 2019 (COVID-19) pandemic in a multicenter health care system.

Methods: A retrospective observational study was conducted to identify all hospitalized neurosurgical patients positive for COVID-19 from March 11, 2020 to November 2, 2020 at Mayo Clinic and the Mayo Clinic Health System.

Results: Eleven hospitalized neurosurgical patients (0.68%) were positive for COVID-19. Four patients (36.6%) were men and 7 (63.3%) were women. The mean age was 65.7 years (range, 35-81 years). All patients had comorbidities. The mean length of stay was 13.4 days (range, 4-30 days). Seven patients had a central nervous system malignancy (4 metastases, 1 meningioma, 1 glioblastoma, and 1 schwannoma). Three patients presented with cerebrovascular complications, comprising 2 spontaneous intraparenchymal hemorrhages and 1 ischemic large-vessel stroke. One patient presented with an unstable traumatic spinal burst fracture. Four patients underwent neurosurgical/neuroendovascular interventions. Discharge disposition was to home in 5 patients, rehabilitation facility in 3, and hospice in 3. Five patients had died at follow-up, 3 within 30 days from COVID-19 complications and 2 from progression of their metastatic cancer.

Conclusions: COVID-19 is rare among the inpatient neurosurgical population. In all cases, patients had multiple comorbidities. All symptomatic patients from the respiratory standpoint had complications during their hospitalization. Deaths of 3 patients who died within 30 days of hospitalization were all related to COVID-19 complications. Neurosurgical procedures were performed only if deemed emergent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2021.06.147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257398PMC
July 2021

Initial Results of Precision Treatment of Postoperative Cerebrospinal Fluid Leak with Ultrasound-Guided Epidural Blood Patch.

World Neurosurg 2021 Sep 25;153:e204-e212. Epub 2021 Jun 25.

Department of Anesthesiology, Mayo Clinic, Jacksonville, Florida, USA.

Background: Incidental durotomy, a known complication of spinal surgery, can lead to persistent cerebrospinal fluid leak and pseudomeningocele if unrecognized or incompletely repaired. We describe the use of ultrasound to visualize the site of durotomy, observe the aspiration of the pseudomeningocele, and guide the precise application of an ultrasound-guided epidural blood patch (US-EBP), under direct visualization in real time.

Methods: A retrospective review was performed to determine demographic, procedural, and outcome characteristics for patients who underwent US-EBP for symptomatic postoperative pseudomeningocele.

Results: Overall, 48 patients who underwent 49 unique episodes of care were included. The average age and body mass index were 60.5 (±12.6) years and 27.8 (±4.50) kg/m, respectively. The most frequent index operation was laminectomy (24.5%), and 36.7% of surgeries were revision operations. Durotomy was intended or recognized in 73.4% of cases, and the median time from surgery to symptom development was 7 (interquartile range 4-16) days. A total of 61 US-EBPs were performed, with 51.0% of patients experiencing resolution of their symptoms after the first US-EBP. An additional 20.4% were successful with multiple US-EBP attempts. Complications occurred in 14.3% of cases, and the median clinical follow-up was 4.3 (interquartile range 2.4-14.5) months.

Conclusions: This manuscript represents the largest series in the literature describing US-EBP for the treatment of postoperative pseudomeningocele. The success rate suggests that routine utilization of US-guided EBP may allow for targeted treatment of pseudomeningoceles, without the prolonged hospitalization associated with lumbar drains or the risks of general anesthesia and impaired wound healing associated with surgical revision.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2021.06.090DOI Listing
September 2021

Migratory strategy drives species-level variation in bird sensitivity to vegetation green-up.

Nat Ecol Evol 2021 07 29;5(7):987-994. Epub 2021 Apr 29.

Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA, USA.

Animals and plants are shifting the timing of key life events in response to climate change, yet despite recent documentation of escalating phenological change, scientists lack a full understanding of how and why phenological responses vary across space and among species. Here, we used over 7 million community-contributed bird observations to derive species-specific, spatially explicit estimates of annual spring migration phenology for 56 bird species across eastern North America. We show that changes in the spring arrival of migratory birds are coarsely synchronized with fluctuations in vegetation green-up and that the sensitivity of birds to plant phenology varied extensively. Bird arrival responded more synchronously with vegetation green-up at higher latitudes, where phenological shifts over time are also greater. Critically, species' migratory traits explained variation in sensitivity to green-up, with species that migrate more slowly, arrive earlier and overwinter further north showing greater responsiveness to earlier springs. Identifying how and why species vary in their ability to shift phenological events is fundamental to predicting species' vulnerability to climate change. Such variation in sensitivity across taxa, with long-distance neotropical migrants exhibiting reduced synchrony, may help to explain substantial declines in these species over the last several decades.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41559-021-01442-yDOI Listing
July 2021

Current and time-lagged effects of climate on innate immunity in two sympatric snake species.

Ecol Evol 2021 Apr 16;11(7):3239-3250. Epub 2021 Feb 16.

Westmont College Santa Barbara CA USA.

Changing environments result in alterations at all levels of biological organization, from genetics to physiology to demography. The increasing frequency of droughts worldwide is associated with higher temperatures and reduced precipitation that can impact population persistence via effects on individual immune function and survival.We examined the effects of annual climate variation on immunity in two sympatric species of garter snakes from four populations in California over a seven-year period that included the record-breaking drought.We examined three indices of innate immunity: bactericidal competence (BC), natural antibodies (NABs), and complement-mediated lysis (CL).Precipitation was the only climatic variable explaining variation in immune function: spring precipitation of the current year was positively correlated to BC and NABs, whereas spring precipitation of the previous year was positively correlated to BC and NABs. This suggests that experiences a physiological time-lag in response to reduced precipitation, which may reflect lack of capital for investment in immunity in the year following a dry year.In general, our findings demonstrate compelling evidence that climate can influence wild populations through effects on physiological processes, suggesting that physiological indices such as these may offer valuable opportunities for monitoring the effects of climate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ece3.7273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019058PMC
April 2021

Accommodating the role of site memory in dynamic species distribution models.

Ecology 2021 05 22;102(5):e03315. Epub 2021 Apr 22.

U.S. Geological Survey, Patuxent Wildlife Research Center, 1 Migratory Way, Turners Falls, Massachusetts, 01376, USA.

First-order dynamic occupancy models (FODOMs) are a class of state-space model in which the true state (occurrence) is observed imperfectly. An important assumption of FODOMs is that site dynamics only depend on the current state and that variations in dynamic processes are adequately captured with covariates or random effects. However, it is often difficult to understand and/or measure the covariates that generate ecological data, which are typically spatiotemporally correlated. Consequently, the non-independent error structure of correlated data causes underestimation of parameter uncertainty and poor ecological inference. Here, we extend the FODOM framework with a second-order Markov process to accommodate site memory when covariates are not available. Our modeling framework can be used to make reliable inference about site occupancy, colonization, extinction, turnover, and detection probabilities. We present a series of simulations to illustrate the data requirements and model performance. We then applied our modeling framework to 13 yr of data from an amphibian community in southern Arizona, USA. In this analysis, we found residual temporal autocorrelation of population processes for most species, even after accounting for long-term drought dynamics. Our approach represents a valuable advance in obtaining inference on population dynamics, especially as they relate to metapopulations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ecy.3315DOI Listing
May 2021

The Impact of Demographic, Clinical, and Institutional Factors on Psychiatric Inpatient Length-of-Stay.

Adm Policy Ment Health 2021 07 1;48(4):683-694. Epub 2021 Jan 1.

BC Centre for Disease Control, 655 W 12th Ave, Vancouver, BC, V5Z 4R4, Canada.

The average length of inpatient stay (LOS) for psychiatric care has declined substantially across Canada and the United States during the past two decades. Although LOS is based presumably on patient, hospital, and community factors, there is little understanding of how such factors are linked with LOS. The purpose of this study was to explore potential individual and systemic factors associated with LOS in a large-scale, longitudinal dataset. Study participants consisted of individuals 11 years of age and older admitted for psychiatric conditions to a New Brunswick hospital between April 1, 2003 and March 31, 2014 (N = 51,865). The study used a retrospective cohort design examining data from the New Brunswick Discharge Abstract Database, administrative data comprised of all inpatient admissions across provincial hospitals. Hierarchical regression analysis was used to estimate the association of individual, facility, and system-level factors with psychiatric LOS. Results indicated that hospital-level factors and individual-level characteristics (i.e., discharge disposition, aftercare referral, socioeconomic status (SES)) account for significant variability in LOS. Consistent with extant literature, our results found that hospital, clinical, and individual factors together are associated with LOS. Furthermore, our results highlight demographic factors surrounding living situation and available financial supports, as well as the match or mismatch between preferred language and language in which services are offered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10488-020-01104-4DOI Listing
July 2021

Timely intervention and control of a novel coronavirus (COVID-19) outbreak at a large skilled nursing facility-San Francisco, California, 2020.

Infect Control Hosp Epidemiol 2020 Dec 14:1-8. Epub 2020 Dec 14.

California Department of Public Health, Richmond, California.

Objective: To describe epidemiologic and genomic characteristics of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in a large skilled-nursing facility (SNF), and the strategies that controlled transmission.

Design, Setting, And Participants: This cohort study was conducted during March 22-May 4, 2020, among all staff and residents at a 780-bed SNF in San Francisco, California.

Methods: Contact tracing and symptom screening guided targeted testing of staff and residents; respiratory specimens were also collected through serial point prevalence surveys (PPSs) in units with confirmed cases. Cases were confirmed by real-time reverse transcription-polymerase chain reaction testing for SARS-CoV-2, and whole-genome sequencing (WGS) was used to characterize viral isolate lineages and relatedness. Infection prevention and control (IPC) interventions included restricting from work any staff who had close contact with a confirmed case; restricting movement between units; implementing surgical face masking facility-wide; and the use of recommended PPE (ie, isolation gown, gloves, N95 respirator and eye protection) for clinical interactions in units with confirmed cases.

Results: Of 725 staff and residents tested through targeted testing and serial PPSs, 21 (3%) were SARS-CoV-2 positive: 16 (76%) staff and 5 (24%) residents. Fifteen cases (71%) were linked to a single unit. Targeted testing identified 17 cases (81%), and PPSs identified 4 cases (19%). Most cases (71%) were identified before IPC interventions could be implemented. WGS was performed on SARS-CoV-2 isolates from 4 staff and 4 residents: 5 were of Santa Clara County lineage and the 3 others were distinct lineages.

Conclusions: Early implementation of targeted testing, serial PPSs, and multimodal IPC interventions limited SARS-CoV-2 transmission within the SNF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/ice.2020.1375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144818PMC
December 2020

The influence of species life history and distribution characteristics on species responses to habitat fragmentation in an urban landscape.

J Anim Ecol 2021 03 1;90(3):685-697. Epub 2021 Feb 1.

U.S. Geological Survey, Western Ecological Research Center, San Diego, CA, USA.

Fragmentation within urbanized environments often leads to a loss of native species diversity; however, variation exists in responses among-species and among-populations within species. We aimed to identify patterns in species biogeography in an urbanized landscape to understand anthropogenic effects on vertebrate communities and identify species that are more sensitive or resilient to landscape change. We investigated patterns in species richness and species responses to fragmentation in southern Californian small vertebrate communities using multispecies occupancy models and determined factors associated with overall commonness and sensitivity to patch size for 45 small vertebrate species both among and within remaining non-developed patches. In general, smaller patches had fewer species, with amphibian species richness being particularly sensitive to patch size effects. Mammals were generally more common, occurring both in a greater proportion of patches and a higher proportion of the sites within occupied patches. Alternatively, amphibians were generally restricted to larger patches but were more ubiquitous within smaller patches when occupied. Species range size was positively correlated with how common a species was across and within patches, even when controlling for only patches that fell within a species' range. We found sensitivity to patch size was greater for more fecund species and depended on where the patch occurred within a species' range. While all taxa were more likely to occur in patches in the warmer portions of their ranges, amphibians and mammals were more sensitive to fragmentation in these warmer areas as compared to the rest of their ranges. Similarly, amphibians occurred at a smaller proportion of sites within patches in drier portions of their ranges. Mammals occurred at a higher proportion of sites that were also in drier portions of their range while reptiles did not differ in their sensitivity to patch size by range position. We demonstrate that taxonomy, life history, range size and range position can predict commonness and sensitivity of species across this highly fragmented yet biodiverse landscape. The impacts of fragmentation on species communities within an urban landscape depend on scale, with differences emerging among and within species and populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1365-2656.13403DOI Listing
March 2021

Identification of Presymptomatic and Asymptomatic Cases Using Cohort-Based Testing Approaches at a Large Correctional Facility-Chicago, Illinois, USA, May 2020.

Clin Infect Dis 2021 03;72(5):e128-e135

Cermak Health Services, Chicago, Illinois, USA.

Background: Coronavirus disease 2019 (COVID-19) continues to cause significant morbidity and mortality worldwide. Correctional and detention facilities are at high risk of experiencing outbreaks. We aimed to evaluate cohort-based testing among detained persons exposed to laboratory-confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in order to identify presymptomatic and asymptomatic cases.

Methods: During 1-19 May 2020, 2 testing strategies were implemented in 12 tiers or housing units of the Cook County Jail, Chicago, Illinois. Detained persons were approached to participate in serial testing (n = 137) and offered tests at 3 time points over 14 days (day 1, days 3-5, and days 13-14). The second group was offered a single test and interview at the end of a 14-day quarantine period (day 14 group) (n = 87).

Results: 224 detained persons were approached for participation and, of these, 194 (87%) participated in ≥1 interview and 172 (77%) had ≥1 test. Of the 172 tested, 19 were positive for SARS-CoV-2. In the serial testing group, 17 (89%) new cases were detected, 16 (84%) on day 1, 1 (5%) on days 3-5, and none on days 13-14; in the day 14 group, 2 (11%) cases were identified. More than half (12/19; 63%) of the newly identified cases were presymptomatic or asymptomatic.

Conclusions: Our findings highlight the utility of cohort-based testing promptly after initiating quarantine within a housing tier. Cohort-based testing efforts identified new SARS-CoV-2 asymptomatic and presymptomatic infections that may have been missed by symptom screening alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciaa1802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799274PMC
March 2021

Prevalence of Intracranial Aneurysms in Patients with Infrarenal Abdominal Aortic Aneurysms: A Multicenter Experience.

Int J Angiol 2020 Dec 27;29(4):229-236. Epub 2020 Jun 27.

Department of Neurology, Mayo Clinic, Jacksonville, Florida.

Prior studies suggest high prevalence of intracranial aneurysms (IA) in patients with infrarenal abdominal aortic aneurysms (AAA). We reviewed our multicenter experience in clinical detection/treatment of IAs in AAA patients and estimated the risk of IA in patients with AAA relative to patients without AAA. We reviewed cases of vascular surgery infrarenal AAA repairs at three Mayo Clinic sites from January 1998 to December 2018. Concurrent controls were randomly matched in a 1:1 ratio by age, sex, smoking history, and head imaging characteristics. Conditional logistic regression was used to calculate odds ratios. We reviewed 2,300 infrarenal AAA repairs. Mean size of AAA at repair was 56.9 ± 11.4 mm; mean age at repair, 75.8 ± 8.0 years. 87.5% of the cases (  = 2014) were men. Head imaging was available in 421 patients. Thirty-seven patients were found to have 45 IAs for a prevalence of 8.8%. Mean size of IA was 4.6 ± 3.5 mm; mean age at IA detection, 72.0 ± 10.8 years. Thirty (81%) out of 37 patients were men. Six patients underwent treatment for IA: four for ruptured IAs and two for unruptured IAs. All were diagnosed before AAA repair. Treatment included five clippings and one coil-assisted stenting. Time from IA diagnosis to AAA repair was 16.4 ± 11.0 years. Two of these patients presented with ruptured AAA, one with successful repair and a second one that resulted in death. Odds of IA were higher for patients with AAA versus those without AAA (8.8% [37/421] vs. 3.1% [13/421]; OR 3.18; 95% confidence interval, 1.62-6.27,  < 0.001). Co-prevalence of IA among patients with AAA was 8.8% and is more than three times the rate seen in patients without AAA. All IAs were diagnosed prior to AAA repair. Surveillance for AAA after IA treatment could have prevented two AAA ruptures and one death.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0040-1713139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690990PMC
December 2020

Inference in artificial intelligence with deep optics and photonics.

Nature 2020 12 2;588(7836):39-47. Epub 2020 Dec 2.

École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

Artificial intelligence tasks across numerous applications require accelerators for fast and low-power execution. Optical computing systems may be able to meet these domain-specific needs but, despite half a century of research, general-purpose optical computing systems have yet to mature into a practical technology. Artificial intelligence inference, however, especially for visual computing applications, may offer opportunities for inference based on optical and photonic systems. In this Perspective, we review recent work on optical computing for artificial intelligence applications and discuss its promise and challenges.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-020-2973-6DOI Listing
December 2020

Visible-Light Optical Coherence Tomography Fibergraphy for Quantitative Imaging of Retinal Ganglion Cell Axon Bundles.

Transl Vis Sci Technol 2020 10 9;9(11):11. Epub 2020 Oct 9.

Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.

Purpose: To develop a practical technique for visualizing and quantifying retinal ganglion cell (RGC) axon bundles .

Methods: We applied visible-light optical coherence tomography (vis-OCT) to image the RGC axon bundles, referred to as vis-OCT fibergraphy, of healthy wild-type C57BL/6 mice. After vis-OCT imaging, retinas were flat-mounted, immunostained with anti-beta-III tubulin (Tuj1) antibody for RGC axons, and imaged with confocal microscopy. We quantitatively compared the RGC axon bundle networks imaged by vis-OCT and confocal microscopy using semi-log Sholl analysis.

Results: Side-by-side comparison of confocal microscopy and vis-OCT confirmed that vis-OCT fibergraphy captures true RGC axon bundle networks. The semi-log Sholl regression coefficients extracted from vis-OCT fibergrams (3.7 ± 0.8 mm) and confocal microscopy (3.6 ± 0.3 mm) images also showed good agreement with each other ( = 6).

Conclusions: We demonstrated the feasibility of using vis-OCT fibergraphy to visualize RGC axon bundles. Further applying Sholl analysis has the potential to identify biomarkers for non-invasively assessing RGC health.

Translational Relevance: Our novel technique for visualizing and quantifying RGC axon bundles provides a potential measurement tool for diagnosing and tracking the progression of optic neuropathies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/tvst.9.11.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552935PMC
October 2020

Programmable photonic circuits.

Nature 2020 10 7;586(7828):207-216. Epub 2020 Oct 7.

Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy.

The growing maturity of integrated photonic technology makes it possible to build increasingly large and complex photonic circuits on the surface of a chip. Today, most of these circuits are designed for a specific application, but the increase in complexity has introduced a generation of photonic circuits that can be programmed using software for a wide variety of functions through a mesh of on-chip waveguides, tunable beam couplers and optical phase shifters. Here we discuss the state of this emerging technology, including recent developments in photonic building blocks and circuit architectures, as well as electronic control and programming strategies. We cover possible applications in linear matrix operations, quantum information processing and microwave photonics, and examine how these generic chips can accelerate the development of future photonic circuits by providing a higher-level platform for prototyping novel optical functionalities without the need for custom chip fabrication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-020-2764-0DOI Listing
October 2020

Mapping angiography and transarterial technetium macroaggregated albumin particle simulation of recurrent atypical intracranial meningioma: feasibility for potential vascular brachytherapy.

Radiol Case Rep 2020 Nov 11;15(11):2278-2281. Epub 2020 Sep 11.

Department of Neurological Surgery, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224, USA.

Atypical meningioma (AM) (WHO-II) has a recurrence rate of 28% after gross total resection (GTR) with limited salvage options. Transarterial therapies may provide treatment opportunities in AM patients who exhausted standard-of-care therapy. In cases where favorable tumor vasculature and particle simulation demonstrate acceptable target dose, Yttrium-90 trans-arterial radioemobilization (TARE) could theoretically provide salvage therapy. A 67-year-old man presented with recurrent AM post gross total resection with adjuvant radiotherapy in 2012, 2014, and 2016. The patient was deemed a poor candidate for additional therapies. Tumor vasculature mapping was performed to determine TARE candidacy. Super-selective angiography and contrast-enhanced cone-beam computed tomography angiosomes demonstrated predominant pial collaterals and minor supply from a middle meningeal artery branch. Particle simulation was performed by infusing 0.3 mCi of 99mTc-macroaggregated albumin (99mTc-MAA). SPECT/CT-MRI fusion demonstrated conformal activity solely within the tumor volume perfused by the middle meningeal artery branch with a lung shunt fraction of 54.7%. The patient subsequently received off-label Nivolumab (PD-1 inhibitor). Mapping angiography for AM using 99mTc-MAA is feasible. It may identify candidates for TARE and potential AM patients with favorable blood supply. The potential for conformal intracranial vascular brachytherapy is intriguing, however, altered arterial supply in recurrent tumors is challenging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radcr.2020.07.051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494606PMC
November 2020

The untapped potential of reptile biodiversity for understanding how and why animals age.

Funct Ecol 2020 Jan 9;34(1):38-54. Epub 2019 Sep 9.

Department of Ecology, Evolution, and Organismal Biology, Iowa State University, Ames, Iowa, 50010, USA.

1. The field of comparative aging biology has greatly expanded in the past 20 years. Longitudinal studies of populations of reptiles with a range of maximum lifespans have accumulated and been analyzed for evidence of mortality senescence and reproductive decline. While not as well represented in studies of amniote senescence, reptiles have been the subjects of many recent demographic and mechanistic studies of the biology of aging. 2. We review recent literature on reptile demographic senescence, mechanisms of senescence, and identify unanswered questions. Given the ecophysiological and demographic diversity of reptiles, what is the expected range of reptile senescence rates? Are known mechanisms of aging in reptiles consistent with canonical hallmarks of aging in model systems? What are the knowledge gaps in our understanding of reptile aging? 3. We find ample evidence of increasing mortality with advancing age in many reptiles. Testudines stand out as slower aging than other orders, but data on crocodilians and tuatara are sparse. Sex-specific analyses are generally not available. Studies of female reproduction suggest that reptiles are less likely to have reproductive decline with advancing age than mammals. 4. Reptiles share many physiological and molecular pathways of aging with mammals, birds, and laboratory model organisms. Adaptations related to stress physiology coupled with reptilian ectothermy suggest novel comparisons and contrasts that can be made with canonical aging phenotypes in mammals. These include stem cell and regeneration biology, homeostatic mechanisms, IIS/TOR signaling, and DNA repair. 5. To overcome challenges to the study of reptile aging, we recommend extending and expanding long-term monitoring of reptile populations, developing reptile cell lines to aid cellular biology, conducting more comparative studies of reptile morphology and physiology sampled along relevant life-history axes, and sequencing more reptile genomes for comparative genomics. Given the diversity of reptile life histories and adaptations, achieving these directives will likely greatly benefit all aging biology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1365-2435.13450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480806PMC
January 2020

Safety, Tolerability, and Efficacy of Pain Reduction by Gabapentin for Acute Headache and Meningismus After Aneurysmal Subarachnoid Hemorrhage: A Pilot Study.

Front Neurol 2020 28;11:744. Epub 2020 Jul 28.

Department of Neurology, Mayo Clinic, Jacksonville, FL, United States.

Severe, often sudden-onset headache is the principal presenting symptoms of aneurysmal subarachnoid hemorrhage (aSAH). We hypothesized that gabapentin would be safe and tolerable for aSAH-induced headaches and would reduce concurrent opioid use. We performed a single-center, double-blind, randomized, placebo-controlled trial (registered at ClinicalTrials.gov; NCT02330094) from November 24, 2014, to June 24, 2017, where aSAH patients received either dose-escalating gabapentin or oral placebo, both alongside a standard of care pain regimen. After 7 days, patients had the option to continue in an open-label period until 14 days after enrollment or until discharge from the intensive care unit. Our primary endpoint was the efficacy of gabapentin in reducing headache numeric pain scores and opioid usage in patients with aSAH compared to the placebo group. We identified 63 potential patients with aSAH for the study. After applying stringent exclusion criteria, 16 eligible patients were enrolled into one of two arms. The study ended prematurely after reaching a pre-specified funding period and an unexpected drop in aSAH cases. There was a trend toward lower headache numeric pain scores and opioid use in the gabapentin treated arm; however this was not significantly different. Gabapentin was well tolerated by participants and no adverse effects were reported. While there was a trend toward lower pain scores and opioid requirement in the gabapentin group, the study was underpowered to detect a difference. Larger multicenter trials are required to evaluate the efficacy of gabapentin to reduce opioid requirements after aSAH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2020.00744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399216PMC
July 2020

Survival Outcomes by Fetal Weight Discordance after Laser Surgery for Twin-Twin Transfusion Syndrome Complicated by Donor Fetal Growth Restriction.

Fetal Diagn Ther 2020 Jul 31:1-10. Epub 2020 Jul 31.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA,

Introduction: Management options for treatment of twin-twin transfusion syndrome (TTTS) with severe donor intrauterine growth restriction (IUGR) include fetoscopic laser surgery and umbilical cord occlusion (UCO). We studied perinatal survival outcomes in this select group after laser surgery, stratifying patients by preoperative estimated fetal weight (EFW) discordance.

Methods: In this retrospective study of monochorionic diamniotic twin gestations with TTTS and selective donor IUGR who underwent laser surgery (2006-2017), preoperative EFW discordance was calculated ([(larger twin - smaller twin)/(larger twin)] × 100) and cases were divided into discordance strata. Severe EFW discordance was defined as >35%. The primary outcome was 30-day donor twin neonatal survival.

Results: The 371 cases were distributed by discordance strata: ≤20% (74 [19.9%]), 21-25% (49 [13.2%]), 26-30% (68 [18.3%]), 31-35% (53 [14.3%]), 36-40% (51 [13.7%]), 41-45% (38 [10.2%]), >45% (38 [10.2%]). Donor 30-day survival declined as the discordance strata increased: 86.5, 85.7, 83.8, 75.5, 64.7, 63.2, and 65.8% (p = 0.0046); 30-day survival was inversely associated with severe discordance (>35%) (64.6 vs. 83.2%, p < 0.0001).

Discussion: In TTTS cases complicated by donor IUGR with severe growth discordance, laser surgery was associated with donor survivorship greater than 60% suggesting that, in this setting, laser surgery remains a reasonable alternative treatment to UCO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000509032DOI Listing
July 2020

Contemporary Management of Acute Ischemic Stroke Across the Continuum: From TeleStroke to Intra-Arterial Management.

Mayo Clin Proc 2020 07;95(7):1512-1529

Departments of Neurology and Neurologic Surgery, Mayo Clinic, Jacksonville, FL.

In this comprehensive contemporary review of acute ischemic stroke management, what is new and different will be highlighted beginning with prehospital stroke systems of care, emergency medical systems, and mobile stroke units, followed by hospital stroke teams, emergency evaluation, telemedicine, and brain and vascular imaging, and finishing with emergency treatments including thrombolysis and mechanical thrombectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mayocp.2020.04.002DOI Listing
July 2020

Longitudinal examination of youth readmission to mental health inpatient units.

Child Adolesc Ment Health 2020 11 3;25(4):238-248. Epub 2020 Mar 3.

Sobey School of Business, Saint Mary's University, Halifax, NS, Canada.

Objective: Significant barriers exist for youth in obtaining mental health services. These barriers are exacerbated by growing demand, attributed partially to children and adolescents who have repeat hospital admissions. The purpose of this study was to identify demographic, socioeconomic and clinical predictors of readmission to inpatient psychiatric services in New Brunswick, Canada.

Method: Key demographic, support and clinical predictors of readmission were identified. The New Brunswick Discharge Abstract Database (DAD) was used to compile a cohort of all children and adolescents ages 3-19 years with psychiatric hospital admissions between 1 April 2003 and 31 March 2014 (N = 3825). Primary analyses consisted of Kaplan-Meier survival methods with log-rank tests to assess time-to-readmission variability, and Cox regression to identify significant predictors of readmission.

Results: In total, 27.8% of admitted children and adolescents experienced at least one readmission within the 10-year period, with 57.3% readmitted to hospital within 90 days following discharge. Bivariate results indicated that male, upper-middle socioeconomic status (SES) youths aged 11-15 years from nonrural communities were most likely to be readmitted. Notable predictors of increased readmission likelihood were older age, being male, higher SES, referral to care by medical practitioner, discharge to another health facility, psychosis, and previous psychiatric admission.

Conclusion: A significant portion of the variance in readmission was accounted for by youth demographic characteristics (i.e. age, SES, geographic location) and various support structures, including referrals to inpatient care and aftercare support services.

Key Practitioner Message: Readmission to inpatient psychiatric care among youth is affected by a number of multifaceted risk factors across individual, environmental and clinical domains. This study used provincial population-scale longitudinal administrative data to demonstrate the influence of various individual and demographic factors on likelihood of readmission, which is notably absent from the majority of studies that make use of smaller, short-term data samples. Ensuring that multiple factors outside of the clinical context are considered when examining readmission among youth may contribute to a more thorough understanding of youth hospitalization patterns.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/camh.12371DOI Listing
November 2020

Spectrally dependent roll-off in visible-light optical coherence tomography.

Opt Lett 2020 May;45(9):2680-2683

Recent development of visible-light optical coherence tomography (vis-OCT) has introduced new applications for noninvasive spectroscopic imaging. However, the measured spectra may be altered by spectrally dependent roll-off (SDR). We formulated a mathematical model for SDR that accounted for nonuniform wavenumber spacing, optical aberrations, and misalignments in the spectrometer. We simulated SDR based on this model and found strong agreement with measurements from a vis-OCT system. We verified that SDR altered spectroscopic measurements of fully oxygenated blood. We corrected these alterations by normalizing each spectrally dependent A-line by the measured SDR of the spectrometer. Our investigations of SDR are critical for informing OCT spectrometer design, alignment, and spectroscopic measurements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OL.389240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194246PMC
May 2020

In Vivo Imaging of Schlemm's Canal and Limbal Vascular Network in Mouse Using Visible-Light OCT.

Invest Ophthalmol Vis Sci 2020 02;61(2):23

,.

Purpose: To validate the ability of visible-light optical coherence tomography (vis-OCT) in imaging the full Schlemm's canal (SC) and its surrounding limbal vascular network in mice in vivo through a compound circumlimbal scan.

Methods: We developed an anterior segment vis-OCT system and a compound circumlimbal scanning method, which montages eight rotated raster scans. We calibrated the circumlimbal scan geometry using a three-dimensional printed phantom eyeball before imaging wild-type C57BL/6J mice. We measured SC size by segmenting SC cross sections from vis-OCT B-scan images and imaged the limbal microvascular network using vis-OCT angiography (vis-OCTA). To introduce changes in SC size, we used a manometer to adjust the intraocular pressure (IOP) to different levels. To create additional optical scattering contrast to enhance SC imaging, we surgically increased the episcleral venous pressure (EVP) and caused blood reflux into SC.

Results: Using the compound circumlimbal scan, our anterior segment vis-OCT noninvasively imaged the full SC and limbal microvascular network in mouse for the first time. We observed an average 123% increase in SC volume when we decreased the IOP by 10 mm Hg from the baseline IOP of 7 to 10 mm Hg and an average 72% decrease in SC volume when the IOP level was elevated by 10 mm Hg from the baseline IOP. We also observed location-dependent SC size responses to IOP changes. Blood reflux caused by increased EVP enabled vis-OCTA to directly visualize SC, which matched well with the segmented SC.

Conclusions: Vis-OCT and vis-OCTA can accurately image the entire SC and limbal microvascular network in vivo using the compound circumlimbal scan. Vis-OCT is also able to quantitatively measure SC responses to changing IOP levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.61.2.23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326574PMC
February 2020

Endovascular Thrombectomy for Acute Ischemic Stroke.

Curr Cardiol Rep 2019 08 30;21(10):112. Epub 2019 Aug 30.

Department of Neurologic Surgery, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.

Purpose Of Review: To review the current evidence supporting the use of endovascular thrombectomy (EVT) for the treatment of acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion (LVO).

Recent Findings: Recent advances in AIS management by EVT have led to significant reduction in morbidity and mortality in selected patients with LVO within the anterior circulation. Until recently, use of EVT was strictly based on time criteria, within 4.5 to 12 h of symptom onset with many patients presenting with "wake-up" stroke who were not considered for EVT. The positive results of the DAWN and DEFUSE-3 trials have shown benefit in extending the therapeutic window for EVT to 24 and 16 h, respectively, after last known normal (LKN) time in the setting of large ischemic penumbra. These trials represent a paradigm shift in contemporary treatment of AIS, changing from a purely time-based decision to treat to an individualized decision based on clinical and radiographic findings of salvageable tissue. Overall, acute stroke management has evolved considerably over the years from intravenous thrombolysis to include EVT, with paralleled improvements in patient selection and thrombectomy devices. Since the results of the DAWN and DEFUSE-3, EVT is now considered the standard of care in select patients with anterior circulation LVO up to 24 h from LKN time. Despite these developments, post-stroke disability remains pervasive and further studies are warranted in establishing the role of EVT in posterior circulation and distal vessel occlusions, with need for development of new and effective techniques for revascularization of small vessels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11886-019-1217-6DOI Listing
August 2019

Tourist photographs as a scalable framework for wildlife monitoring in protected areas.

Curr Biol 2019 07;29(14):R681-R682

School of Environmental and Life Sciences, University of Newcastle, Newcastle, NSW 2308, Australia; Centre for African Conservation Ecology, Nelson Mandela University, Port Elizabeth, 6031, South Africa.

Protected areas are critical to conservation efforts in the face of rapid biodiversity declines [1]. Yet the resources for conservation are often limited and shared amongst many competing priorities [2]. As a consequence, even basic monitoring surveys are absent within most protected areas [3]. Although a range of wildlife monitoring methods exist, considerable focused survey effort is often required to yield accurate and precise estimates [4]. This makes monitoring difficult to sustain or replicate, limiting access to the data required for evidence-based conservation decisions. Citizen-scientists have been proposed as an important complement to the finite resources available for basic monitoring within protected areas [5]; however, the full potential of this approach has yet to be realised. Wildlife tourists and guides are especially focussed on encountering and photographing fauna and flora, yet the data collected in these efforts is rarely harnessed for conservation monitoring within protected areas. A detailed understanding of photographic tourism's potential role in wildlife monitoring has been lacking, but is essential for the development of new tools to harness the data being collected through tourism. Here, we demonstrate that tourist-contributed data can aid wildlife monitoring in protected areas by providing population estimates of large carnivores comparable to those from traditional survey methods. Our approach could capitalize upon the immense number of wildlife photographs being taken daily as part of the global > 30-billion USD, wildlife-based tourism industry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cub.2019.05.056DOI Listing
July 2019

Experimental band structure spectroscopy along a synthetic dimension.

Nat Commun 2019 Jul 16;10(1):3122. Epub 2019 Jul 16.

Ginzton Laboratory and Department of Electrical Engineering, Stanford University, Stanford, CA, 94305, USA.

There has been significant recent interest in synthetic dimensions, where internal degrees of freedom of a particle are coupled to form higher-dimensional lattices in lower-dimensional physical structures. For these systems, the concept of band structure along the synthetic dimension plays a central role in their theoretical description. Here we provide a direct experimental measurement of the band structure along the synthetic dimension. By dynamically modulating a resonator at frequencies commensurate with its mode spacing, we create a periodically driven lattice of coupled modes in the frequency dimension. The strength and range of couplings can be dynamically reconfigured by changing the modulation amplitude and frequency. We show theoretically and demonstrate experimentally that time-resolved transmission measurements of this system provide a direct readout of its band structure. We also realize long-range coupling, gauge potentials and nonreciprocal bands by simply incorporating additional frequency drives, enabling great flexibility in band structure engineering.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-11117-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635488PMC
July 2019

X-Linked Lymphoproliferative Syndrome Presenting as Adult-Onset Multi-Infarct Dementia.

J Neuropathol Exp Neurol 2019 05;78(5):460-466

Department of Neurology, Mayo Clinic, Jacksonville, Florida.

Pathogenic hemizygous variants in the SH2D1A gene cause X-linked lymphoproliferative (XLP) syndrome, a rare primary immunodeficiency usually associated with fatal Epstein-Barr virus infection. Disease onset is typically in early childhood, and the average life expectancy of affected males is ∼11 years. We describe clinical, radiographic, neuropathologic, and genetic features of a 49-year-old man presenting with central nervous system vasculitis that was reminiscent of adult primary angiitis but which was unresponsive to treatment. The patient had 2 brothers; 1 died of aplastic anemia at age 13 and another died of diffuse large B-cell lymphoma in his sixties. Exome sequencing of the patient and his older brother identified a novel hemizygous variant in SH2D1A (c.35G>T, p.Ser12Ile), which encodes the signaling lymphocyte activation molecule (SLAM)-associated protein (SAP). Molecular modeling and functional analysis showed that this variant had decreased protein stability, similar to other pathogenic missense variants in SH2D1A. The family described in this report highlights the broadly heterogeneous clinical presentations of XLP and the accompanying diagnostic challenges in individuals presenting in adulthood. In addition, this report raises the possibility of a biphasic distribution of XLP cases, some of which may be mistaken for age-related malignancies and autoimmune conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnen/nlz018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467195PMC
May 2019
-->