Treating Chronic Iliac Vein Stent Occlusion in an Office-Based Lab Setting.

Iliac vein stenting is performed when sufficient venous patency is not achieved via angioplasty or lysis. Iliac vein stenting is known to be effective; however, occlusion of the stent occurs occasionally. There is a lack of effective treatment options for those with failed prior venous stents, and traditional methods may involve the removal of the stent and surgical reconstruction. We present a patient with a right leg post-thrombotic syndrome and narcotic abuse after occlusion of a previously placed right common iliac/external iliac vein stent 25 years prior. After transfer to an office-based lab (OBL), femoral vein access was achieved. Then, a second stent was deployed adjacent to the previously chronically thrombosed stent. Imaging confirmed adequate deployment of the new stent and venous flow. Treatment resulted in a significant decrease in patient pain and cessation of narcotics. We demonstrate successful recanalization of a right iliac vein thrombosis via parallel deployment of a stent adjacent to a chronically thrombosed stent.

Modeling the subcutaneous pharmacokinetics of antibodies co-administered with rHuPH20.

Predicting the subcutaneous (SC) pharmacokinetics (PK) of antibodies in humans is challenging, with clinical data currently being the only reliable data source for modeling SC absorption and bioavailability. Recombinant human hyaluronidase PH20 (rHuPH20) is an enzyme that facilitates SC delivery of high-dose, high-volume therapeutics. Numerous monoclonal antibodies have been co-administered SC with rHuPH20 in a clinical setting, establishing an extensive PK database. The goal of this work is to demonstrate how aggregated clinical data can be leveraged in a universal modeling framework for characterizing SC antibody PK, resulting in parameterization that can be used in predictive simulations of new antibodies. Data for 10 individual antibodies co-administered SC with rHuPH20 were obtained from publicly available sources. PK modeling of each antibody was conducted using the same model structure, but uniquely parameterized. The model structure consisted of a two-compartment model to capture linear kinetics, plus a target-binding mechanism to accommodate nonlinear kinetics driven by antibody-target complex formation and elimination. The clinical PK profiles for all antibodies were accurately described using the universal modeling framework. The SC PK parameters of absorption and bioavailability were consistent across the range of antibody and target properties evaluated. SC administration with rHuPH20 yielded a 30% increase in absorption rate on average and similar or better bioavailability. These parameter values can serve as initial conditions for model-based PK predictions for new antibodies co-administered SC with rHuPH20 to enable evaluation of optimal SC dose and schedule regimens prior to and during clinical development.

Primary Canalicular MALT Lymphoma Masquerading as Chronic Canaliculitis.

A 67-year-old female presented with chronic canaliculitis and underwent canalicular marsupialization. During the procedure, a fleshy mass was found in the canaliculus, which was excised completely and sent to pathology. Histology confirmed the diagnosis of extranodal marginal zone mucosa-associated lymphoid tissue lymphoma. The patient underwent staging with positron emission tomography/CT scan, which did not show any hypermetabolic foci elsewhere in the body, so the patient elected to undergo close observation without further treatment. At 12 months of follow-up, the patient has remained disease-free.

A complicated presentation of vertebral coccidioidomycosis dissemination: A case report and discussion.

Coccidioidomycosis, also known as San Joaquin Valley fever, is an illness caused by the dimorphic fungus Coccidioides. Coccidioidomycosis is endemic to desert regions of the Western Hemisphere, including California, Arizona, Utah, Nevada, and New Mexico. We report a case of disseminated coccidioidomycosis in a 42-year-old male. Months after an upper respiratory infection of unidentified origin, the patient began experiencing back pain. The persistence of the back pain prompted MRI and CT imaging, which revealed lytic lesions. His clinical and radiological presentation mimicked, and was originally approached, as if it were a malignancy. Metastasis or multiple myeloma were considered the most likely differential diagnoses. As a result, the patient underwent surgical exploration. Pathology results indicated the presence of a fungal infection, without evidence of malignancy. PCR confirmed the diagnosis of coccidioidomycosis. The patient began treatment with fluconazole 800 mg daily and is anticipated to receive antifungal treatment for an indefinite period.

Heterogeneity in Vaccinal Immunity to SARS-CoV-2 Can Be Addressed by a Personalized Booster Strategy.

SARS-CoV-2 vaccinations were initially shown to substantially reduce risk of severe disease and death. However, pharmacokinetic (PK) waning and rapid viral evolution degrade neutralizing antibody (nAb) binding titers, causing loss of vaccinal protection. Additionally, there is inter-individual heterogeneity in the strength and durability of the vaccinal nAb response. Here, we propose a personalized booster strategy as a potential solution to this problem. Our model-based approach incorporates inter-individual heterogeneity in nAb response to primary SARS-CoV-2 vaccination into a pharmacokinetic/pharmacodynamic (PK/PD) model to project population-level heterogeneity in vaccinal protection. We further examine the impact of evolutionary immune evasion on vaccinal protection over time based on variant fold reduction in nAb potency. Our findings suggest viral evolution will decrease the effectiveness of vaccinal protection against severe disease, especially for individuals with a less durable immune response. More frequent boosting may restore vaccinal protection for individuals with a weaker immune response. Our analysis shows that the ECLIA RBD binding assay strongly predicts neutralization of sequence-matched pseudoviruses. This may be a useful tool for rapidly assessing individual immune protection. Our work suggests vaccinal protection against severe disease is not assured and identifies a potential path forward for reducing risk to immunologically vulnerable individuals.

Evaluation of the Impact of Optical Coherence Tomography on Pediatrician Otologic Examination Judgment.

Accurate diagnosis of otitis media is imperative to judicious antibiotic prescription. Visualization of the tympanic membrane and accurate identification of middle ear effusion with standard otoscopy is inherently challenging in pediatrics, especially in the youngest children who are most at risk for otitis media. With the average diagnostic accuracy among primary care physicians of 50% and accurate identification of normal tympanic membrane versus acute otitis media versus otitis media with effusion ranging from 30% to 84% among pediatricians, there is great opportunity for diagnostic improvement and decreasing unnecessary antibiotic use. In a 96-pediatrician-blinded otoscopy diagnosis quiz, addition of optical coherence tomography, a novel depth-imaging technology, resulted in a 32% improvement in fluid identification, and 21% increase in diagnostic accuracy. This study suggests that the clinical use of this technology promises to improve diagnostic accuracy and antibiotic stewardship in pediatrics.

No magic bullet: Limiting in-school transmission in the face of variable SARS-CoV-2 viral loads.

In the face of a long-running pandemic, understanding the drivers of ongoing SARS-CoV-2 transmission is crucial for the rational management of COVID-19 disease burden. Keeping schools open has emerged as a vital societal imperative during the pandemic, but in-school transmission of SARS-CoV-2 can contribute to further prolonging the pandemic. In this context, the role of schools in driving SARS-CoV-2 transmission acquires critical importance. Here we model in-school transmission from first principles to investigate the effectiveness of layered mitigation strategies on limiting in-school spread. We examined the effect of masks and air quality (ventilation, filtration and ionizers) on steady-state viral load in classrooms, as well as on the number of particles inhaled by an uninfected person. The effectiveness of these measures in limiting viral transmission was assessed for variants with different levels of mean viral load (ancestral, Delta, Omicron). Our results suggest that a layered mitigation strategy can be used effectively to limit in-school transmission, with certain limitations. First, poorly designed strategies (insufficient ventilation, no masks, staying open under high levels of community transmission) will permit in-school spread even if some level of mitigation is present. Second, for viral variants that are sufficiently contagious, it may be difficult to construct any set of interventions capable of blocking transmission once an infected individual is present, underscoring the importance of other measures. Our findings provide practical recommendations; in particular, the use of a layered mitigation strategy that is designed to limit transmission, with other measures such as frequent surveillance testing and smaller class sizes (such as by offering remote schooling options to those who prefer it) as needed.

Exploring the Impact of The NEST Collaborative's Remote Social Intervention on Feelings of Depression and Isolation.

Early evidence of remote, volunteer-led social support interventions to reduce social isolation in older adults has been encouraging; however, evaluation data on outcomes related to social isolation associated from these interventions is scarce. Here, we share programmatic details of a novel, statewide initiative, called the NEST Collaborative, rolled out to meet immediate emotional, informational, and instrumental needs of older adults in Nevada during the COVID-19 pandemic. The evaluation included 31 older adults participating in weekly one-to-one empathy-based phone calls with multi-generational volunteers seeking to enhance participants' social networks through meaningful friendships. The calls were associated with programmatically meaningful, though not statistically significant, improvements in modified Hawthorne Friendship Scale and PHQ-2 Depression Scale scores over two waves of survey responses. These results suggest that social isolation and depression among older adults decreased among our sample over a period of increased isolation and mental health burden across the general population. With the potential for sustained impact in reducing social isolation over time, remote social support programs, such as the NEST Collaborative, may have persistent value long-term, beyond time-limited crisis response contexts.

A Refined Method for Studying Foraging Behaviour and Body Mass in Group-Housed European Starlings.

Laboratory experiments on passerine birds have been important for testing hypotheses regarding the effects of environmental variables on the adaptive regulation of body mass. However, previous work in this area has suffered from poor ecological validity and animal welfare due to the requirement to house birds individually in small cages to facilitate behavioural measurement and frequent catching for weighing. Here, we describe the social foraging system, a novel technology that permits continuous collection of individual-level data on operant foraging behaviour and body mass from group-housed European starlings (Sturnus vulgaris). We report on the rapid acquisition of operant key pecking, followed by foraging and body mass data from two groups of six birds maintained on a fixed-ratio operant schedule under closed economy for 11 consecutive days. Birds gained 6.0 ± 1.2 g (mean ± sd) between dawn and dusk each day and lost an equal amount overnight. Individual daily mass gain trajectories were non-linear, with the rate of gain decelerating between dawn and dusk. Within-bird variation in daily foraging effort (key pecks) positively predicted within-bird variation in dusk mass. However, between-bird variation in mean foraging effort was uncorrelated with between-bird variation in mean mass, potentially indicative of individual differences in daily energy requirements. We conclude that the social foraging system delivers refined data collection and offers potential for improving our understanding of mass regulation in starlings and other species.

Beyond the new normal: Assessing the feasibility of vaccine-based suppression of SARS-CoV-2.

As the COVID-19 pandemic drags into its second year, there is hope on the horizon, in the form of SARS-CoV-2 vaccines which promise disease suppression and a return to pre-pandemic normalcy. In this study we critically examine the basis for that hope, using an epidemiological modeling framework to establish the link between vaccine characteristics and effectiveness in bringing an end to this unprecedented public health crisis. Our findings suggest that a return to pre-pandemic social and economic conditions without fully suppressing SARS-CoV-2 will lead to extensive viral spread, resulting in a high disease burden even in the presence of vaccines that reduce risk of infection and mortality. Our modeling points to the feasibility of complete SARS-CoV-2 suppression with high population-level compliance and vaccines that are highly effective at reducing SARS-CoV-2 infection. Notably, vaccine-mediated reduction of transmission is critical for viral suppression, and in order for partially-effective vaccines to play a positive role in SARS-CoV-2 suppression, complementary biomedical interventions and public health measures must be deployed simultaneously.

Evaluating Elastic-Plastic Wavy and Spherical Asperity-Based Statistical and Multi-Scale Rough Surface Contact Models with Deterministic Results.

The solution to an elastic-plastic rough surface contact problem can be applied to phenomena such as friction and contact resistance. Many different types of models have therefore been developed to solve rough surface contact. A deterministic approach may accurately describe the entire surface, but the computing time is too long for practical use. Thus, mathematically abbreviated models have been developed to describe rough surface contact. Many popular models employ a statistical methodology to solve the contact problem, and they borrow the solution for spherical or parabolic contact to represent individual asperities. However, it is believed that a sinusoidal geometry may be a more realistic asperity representation. This has been applied to a newer version of the stacked multiscale model and statistical models. While no single model can accurately describe every contact problem better than any other, this work aims to help establish guidelines that determine the best model to solve a rough surface contact problem by applying mathematical and deterministic models to two reference surfaces in contact with a rigid flat. The discrepancies and similarities form the basis of those guidelines.

Individually optimal choices can be collectively disastrous in COVID-19 disease control.

BACKGROUND: The word 'pandemic' conjures dystopian images of bodies stacked in the streets and societies on the brink of collapse. Despite this frightening picture, denialism and noncompliance with public health measures are common in the historical record, for example during the 1918 Influenza pandemic or the 2015 Ebola epidemic. The unique characteristics of SARS-CoV-2-its high basic reproduction number (R0), time-limited natural immunity and considerable potential for asymptomatic spread-exacerbate the public health repercussions of noncompliance with interventions (such as vaccines and masks) to limit disease transmission. Our work explores the rationality and impact of noncompliance with measures aimed at limiting the spread of SARS-CoV-2. METHODS: In this work, we used game theory to explore when noncompliance confers a perceived benefit to individuals. We then used epidemiological modeling to predict the impact of noncompliance on control of SARS-CoV-2, demonstrating that the presence of a noncompliant subpopulation prevents suppression of disease spread. RESULTS: Our modeling demonstrates that noncompliance is a Nash equilibrium under a broad set of conditions and that the existence of a noncompliant population can result in extensive endemic disease in the long-term after a return to pre-pandemic social and economic activity. Endemic disease poses a threat for both compliant and noncompliant individuals; all community members are protected if complete suppression is achieved, which is only possible with a high degree of compliance. For interventions that are highly effective at preventing disease spread, however, the consequences of noncompliance are borne disproportionately by noncompliant individuals. CONCLUSIONS: In sum, our work demonstrates the limits of free-market approaches to compliance with disease control measures during a pandemic. The act of noncompliance with disease intervention measures creates a negative externality, rendering suppression of SARS-CoV-2 spread ineffective. Our work underscores the importance of developing effective strategies for prophylaxis through public health measures aimed at complete suppression and the need to focus on compliance at a population level.

Characterization of Subtype Selective Cannabinoid CB2 Receptor Agonists as Potential Anti-Inflammatory Agents.

Activation of the CB2 receptor has been shown to have anti-inflammatory and antinociceptive effects without causing psychoactive effects. Previously, we reported that the compound ethyl 2(2-(N-(2,3-dimethylphenyl) phenylsulfonamido)acetamido)benzoate (ABK5) is a CB2 subtype selective agonist with anti-inflammatory and antinociceptive effects. In the present study, we tested four ABK5 derivatives, ABK5-1, ABK5-2, ABK5-5, and ABK5-6, to analyze the structure of ABK5 to obtain CB2-selective agonists with higher affinity and efficacy. Affinity, subtype selectivity, and G-protein coupling were determined by radioligand binding assays. Selected compounds were then subjected to evaluation of anti-inflammatory effects using two different cell lines, Jurkat (ABK5-1 and 5-2) and BV-2 cells (ABK5-1), which are models of T cells and microglia, respectively. ABK5-1, ABK5-2, and ABK5-6 had comparable CB2 binding affinity with ABK5 (and stimulated G-protein coupling), while only ABK5-1 and ABK5-2 maintained CB2-subtype selectivity. ABK5-5 did not bind CB2 in the detectable range. RT-PCR and ELISA analysis showed that the two compounds also inhibit IL-2 and TNF-α production, and they were more efficacious than ABK5 in inhibiting TNF-α production. CXCL-12 mediated chemotaxis was also evaluated by the transwell migration assay, and both ABK5-1 and ABK5-2 inhibited chemotaxis with a stronger effect observed in ABK5-1. In the microglia cell line BV-2, ABK5-1 inhibited IL-1ß and IL-6 production, which suggests this compound has anti-inflammatory effects through targeting multiple immune cells, and may be a candidate for treatment of inflammation.

In the long shadow of our best intentions: Model-based assessment of the consequences of school reopening during the COVID-19 pandemic.

As the world grapples with the ongoing COVID-19 pandemic, a particularly thorny set of questions surrounds the reopening of primary and secondary (K-12) schools. The benefits of in-person learning are numerous, in terms of education quality, mental health, emotional well-being, equity and access to food and shelter. Early reports suggested that children might have reduced susceptibility to COVID-19, and children have been shown to experience fewer complications than older adults. Over the past few months, our understanding of COVID-19 has been further shaped by emerging data, and it is now understood that children are as susceptible to infection as adults and have a similar viral load during infection, even if asymptomatic. Based on this updated understanding of the disease, we have used epidemiological modeling to explore the feasibility and consequences of school reopening in the face of differing rates of COVID-19 prevalence and transmission. We focused our analysis on the United States, but the results are applicable to other countries as well. We demonstrate the potential for a large discrepancy between detected cases and true infections in schools due to the combination of high asymptomatic rates in children coupled with delays in seeking testing and receiving results from diagnostic tests. Our findings indicate that, regardless of the initial prevalence of the disease, and in the absence of robust surveillance testing and contact-tracing, most schools in the United States can expect to remain open for 20-60 days without the emergence of sizeable disease clusters. At this point, even if schools choose to close after outbreaks occur, COVID-19 cases will be seeded from these school clusters and amplified into the community. Thus, our findings suggest that the debate between the risks to student safety and benefits of in-person learning frames a false dual choice. Reopening schools without surveillance testing and contact tracing measures in place will lead to spread within the schools and within the communities that eventually forces a return to remote learning and leaves a trail of infection in its wake.

In vivo dynamic characterization of the human tympanic membrane using pneumatic optical coherence tomography.

Decreased mobility of the human eardrum, the tympanic membrane (TM), is an essential indicator of a prevalent middle ear infection. The current diagnostic method to assess TM mobility is via pneumatic otoscopy, which provides subjective and qualitative information of subtle motion. In this study, a handheld spectral-domain pneumatic optical coherence tomography system was developed to simultaneously measure the displacement of the TM, air pressure inputs applied to a sealed ear canal, and to perform digital pneumatic otoscopy. A novel approach based on quantitative parameters is presented to characterize spatial and temporal variations of the dynamic TM motion. Furthermore, the TM motions of normal middle ears are compared with those of ears with middle ear infections. The capability of noninvasively measuring the rapid motion of the TM is beneficial to understand the complex dynamics of the human TM, and can ultimately lead to improved diagnosis and management of middle ear infections.

Low-cost, smartphone-based frequency doubling technology visual field testing using a head-mounted display.

BACKGROUND: Current visual field screening machines are bulky and expensive, limiting their accessibility, affordability and use. We report the design and evaluation of a novel, portable, cost-effective system for glaucoma screening using smartphone-based visual field screening using frequency doubling technology (FDT) and a head-mounted display. METHODS: Nineteen eyes of 10 subjects with new-onset or chronic primary open angle glaucoma were tested and compared with the Humphrey Zeiss FDT and the newly developed Mobile Virtual Perimetry (MVP) FDT with the C-20 testing pattern. Mann-Whitney, Bland-Altman and linear regression analyses were performed to assess statistical difference, agreement and correlation, respectively, between the two devices. RESULTS: The average age of the participants was 58±15 years. No statistically significant difference was found between the MVP FDT and the Humphrey Zeiss FDT (p>0.05). Bland-Altman and linear regression analyses demonstrated good agreement and correlation between the two devices. CONCLUSION: The MVP FDT is a low-cost, portable visual field screening device that produces comparable results to the Humphrey Zeiss FDT and may be used as an easily accessible screening tool for glaucoma.

Widefield Fluorescein Angiography in the Fellow Eyes of Patients with Presumed Unilateral Persistent Fetal Vasculature.

PURPOSE: To examine the retinal vascular findings on widefield fluorescein angiography (FA) in the fellow eyes of patients with unilateral persistent fetal vasculature (PFV). DESIGN: Retrospective case series. PARTICIPANTS: Consecutive patients with unilateral PFV evaluated by a single physician at an academic medical center from February 1, 2011, to November 30, 2018. METHODS: Clinical and demographic information, including age, gender, race, ethnicity, affected eye, subtype, stalk origin, complications on presentation, length of follow-up, and examination findings, was reviewed using the electronic medical record. Fluorescein angiograms of the affected and fellow eyes were reviewed by 2 authors for characteristic retinal vascular abnormalities. Agreement between the authors' scores was analyzed using Cohen's Kappa. MAIN OUTCOME MEASURES: Fluorescein angiography abnormalities, including peripheral vessel avascularity, aberrant circumferential vessels, terminal supernumerary branching, regional capillary dropout, terminal bulbing, abnormal choroidal flush, abnormal vessel straightening, and peripheral vessel leakage or dilation. RESULTS: Inclusion criteria were met by 41 patients. The average age at initial visit was 10.0 months. The average length of follow-up was 36.4 months. Abnormalities on FA were seen in 31 (75.6%) fellow eyes: peripheral vessel avascularity in 27.5 (67.1%), aberrant circumferential vessels in 20 (48.8%), terminal supernumerary branching in 17 (41.5%), regional capillary dropout in 9 (22.0%), terminal bulbing in 6 (14.6%), abnormal choroidal flush in 3.5 (8.5%), and abnormal vessel straightening and peripheral vessel leakage in 2.5 (6.1%). Statistical analysis disclosed an overall observed agreement of 93.4% among the raters (κ = 0.84, P < 0.0001). CONCLUSIONS: Retinal vascular abnormalities seen in patients with unilateral PFV were present in the majority of fellow eyes. This suggests that unilateral PFV may in fact be a bilateral, asymmetric process, but the clinical significance of these subtle findings is not known.

Clinical Diagnosis and Histopathologic Features of a Synthetic Fiber Granuloma.

The authors report a case of a synthetic fiber granuloma to demonstrate the challenges in diagnosing these lesions and to highlight their histopathologic features. This is the first report in the literature to use histopatho-logic and immunofluorescence studies to characterize the subtype and distribution of macrophages in synthetic fiber granuloma. [J Pediatr Ophthalmol Strabismus. 2020;57:e92-e95.].