Beyond the Label: Real-World Side Effects Experienced With FDA-Approved Drugs for Non-Melanoma Skin Cancers.

With immunotherapy historically focused on cutaneous melanoma, there has been a new wave of systemic medications available for treating non-melanoma skin cancers including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and Merkel cell carcinoma (MCC). The immune checkpoint inhibitors approved by the FDA target programmed cell death protein 1 (PD-1) and the Hedgehog (Hh) signaling pathway. These medications have expanded treatment options; however, side effects are an important consideration. We used the FDA Adverse Events Reporting System (FAERS) to characterize the most prevalent, real-world side effects experienced by patients on these agents. Muscle spasms (23.45%), alopecia (16.06%), ageusia (12.02%), taste disorder (11.91%), and fatigue (11.67%) were the five most common side effects reported with medications used for BCC treatment. Logistic regression analysis showed males on vismodegib for BCC having greater odds of experiencing muscle spasms (aOR 1.33, P<0.001) and ageusia (aOR 1.34,  P<0.001) versus females, who were more likely to exhibit alopecia (aOR 1.82, P<0.001) and nausea (aOR 1.96, P<0.001). With SCC treatment, the 5 most reported adverse events were fatigue (5.58%), rash (3.59%), asthenia (3.59%), pruritus (3.19%), and pyrexia (2.79%). Patients taking cemiplimab-rwlc for BCC compared to SCC were more likely to experience disease progression (aOR 10.98, P=0.02). With medication labels providing an excessively daunting list of side effects, we characterize practical side effects seen in patients receiving systemic treatments for non-melanoma skin cancers.  J Drugs Dermatol. 2024;23(5):301-305. doi:10.36849/JDD.7968.

Surgical Management of Overgrowth Syndrome With Bilateral Vision-Threatening Ptosis.

We describe the first case reported in ophthalmological literature of the surgical management of a 17-month-old boy with bilateral vision-threatening ptosis, tarsomegaly, ectropion, and euryblepharon secondary to suspected overgrowth syndrome. We elaborate on the major challenges associated with surgical management including the natural and asymmetric growth of oversized tissue, the high likelihood of scarring and formation of disorganized tissue, and risks of frequent intubation in these patients who may have lesions that compromise critical structures such as the airway. Ultimately, surgical intervention is encouraged primarily if vision or ocular health is threatened and secondarily to achieve good cosmesis.

A cross-sectional analysis of medications used by patients reporting alopecia areata on the FDA adverse events reporting system.

BACKGROUND: Alopecia areata (AA) is an autoimmune condition that leads to patchy, nonscarring hair loss. Its etiology remains unknown; the condition can be debilitating for patients, impacting their psychosocial wellbeing. Various triggers have been reported, ranging from genetic predisposition and infections to environmental factors. Medications have also been thought to be an inciting factor in AA. METHODS: Using the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS), all cases reporting AA as an adverse event were used to capture associated medications and patient characteristics. RESULTS: There were 1,331 AA cases reported as an adverse event with medication use. Monoclonal antibodies accounted for 6 out of the top 10 drugs associated with the highest number of AA cases. Males were more likely to report AA when taking adalimumab (OR: 1.79, P = 0.04) and dupilumab (OR: 2.56, P = 0.03) compared to females. Individuals between 42 and 64 years old accounted for 46.7% of AA cases. Lastly, females in older age groups showed greater odds of developing AA compared to males (OR: 1.03, P < 0.01). CONCLUSIONS: Based on the FAERS, there has been a steady rise in AA cases, and monoclonal antibodies were the most frequently cited medication class tied to AA. With a dearth of literature on triggers and patient demographics, we sought to describe features of AA cases that could increase awareness and be used to improve future clinical outcomes in patients.

The association of stroke with herpes zoster ophthalmicus.

BACKGROUND/OBJECTIVES: Studies have reported an association between herpes zoster ophthalmicus (HZO) and stroke. We sought to validate this association with rigorous controls for both medical comorbidities and social factors using a nationwide U.S. administrative medical claims database. SUBJECTS/METHODS: A two-step approach was taken: first a retrospective case-control study was performed, followed by a self-controlled case series (SCCS). For the case control study, cox proportional hazard regression with inverse proportional treatment weighting assessed the hazard for stroke. In the SCCS, incidence of stroke was compared prior to and after the diagnosis of HZO. RESULTS: For the case-control study, 25,720 cases and 75,924 controls met our eligibility criteria. 1712 (6.7%) and 4544 (6.0%) strokes occurred in the case and control groups respectively, conferring an 18% increased risk of stroke in the observed 1-year post-HZO period (HR = 1.18, 95% CI: 1.12-1.25, p < 0.001). SCCS analysis showed the risk for stroke was highest in the month immediately after HZO episode compared to any other time range (1-30 days after, relative risk 1.58, p < 0.001) and even higher when assessing time more distal time points prior to the HZO diagnosis (days 1-30 after HZO diagnosis had RR = 1.69 (95% CI: 1.38-2.07) and RR = 1.93 (95% CI: 1.55-2.39) compared with days -120 to -91 and -150 to -121 prior to index, respectively (p < 0.001). CONCLUSIONS: After accounting for stroke risk factors, our analysis confirms the association between HZO and stroke, with highest risk in the immediate month after an episode.

Real-World Experience With Teprotumumab in Patients With Dysthyroid Optic Neuropathy.

BACKGROUND: Teprotumumab, an insulin-like growth factor I receptor inhibitory antibody, improved proptosis, diplopia, inflammatory signs/symptoms, and quality of life in patients with active thyroid eye disease (TED) in clinical trials. The trials excluded patients with dysthyroid optic neuropathy (DON). Recently, many case reports and case series have reported the successful use of teprotumumab to treat DON. Here, we review the data from published cases and our clinical experience in treating patients having DON with teprotumumab. METHODS: A literature search was conducted of patients with DON treated with teprotumumab from January 2020 through September 2022. Data from DON patients from the authors' (M.A.T. and C.A.B.) clinical practice were included. Primary outcome measure was mean (SD) improvements for visual acuity, color vision, and visual fields. Improvements in proptosis and clinical activity score (CAS) and diplopia were compared before and after teprotumumab administration. RESULTS: Ten observational studies/case reports were identified along with 2 patients in our practice. In all, there were 24 active TED patients with DON (37 eyes) who were treated with teprotumumab. Mean (SD) age was 66.5 (13.6) years and 13 (54%) were females, disease duration ranged from 2 months to >15 years. 22/24 patients had none, minimal improvement or progression of visual loss with intravenous/oral corticosteroids, orbital decompression (n = 9), and orbital radiation (n = 2). There were 2 patients who received teprotumumab as the only therapy. Overall, 88% (21/24) reported improvement in visual acuity after teprotumumab and in 75% (18/24), improvement in vision was observed after just 2 infusions of teprotumumab. Three eyes had decompression surgery in close proximity to teprotumumab infusions and were excluded from analyses. Mean (SD) improvement in visual acuity was 3.73 lines (SD 3.74), range 2-15 lines in 33 eyes. The mean (SD) improvement in the mean deviation on visual field testing in 15 eyes was 5.6 db (3.0 db). Mean (SD) improvement in proptosis was 4.37 mm (SD: 2.11) (20 patients, 32 eyes); and clinical activity score: mean reduction of 5.1 (1.3) for 18 patients. Teprotumumab was well tolerated in all but one patient. Adverse events reported included fatigue, dysgeusia, hearing loss, nausea, hyperglycemia, and muscle spasms. CONCLUSIONS: Teprotumumab is an effective treatment for DON in our experience and in published cases in whom treatment with steroids, surgery, or orbital radiation was unsuccessful.

Missed games, financial losses, and characteristics of eye injuries in the National Basketball Association during the 2010-2011 to 2017-2018 seasons.

PURPOSE: The purpose is to report financial loss, demographic metrics, and mechanisms of injury associated with eye injuries in the National Basketball Association (NBA) from the 2010-2011 to 2017-2018 seasons. METHODS: We performed a retrospective review of eye injuries in the NBA from the 2010-2011 to 2017-2018 seasons using publicly available information from Basketball Reference and the Pro Sports Transactions websites. Only injuries of the eye and adnexa that caused players to miss games in the regular season and playoffs were included in the study. Financial loss was calculated based on the regular season salary of the players and normalized for inflation with 2018 as the base year. RESULTS: There were 30 eye injuries causing a total of 106 missed games and $7,486,770 in financial losses across eight seasons. Linear regressions showed a moderately positive increase in eye injuries (Pearson's r = 0.68, P = 0.07, and 0.79 injuries per year/1000 game-days increase) and financial losses (Pearson's r = 0.67, P = 0.07, and $185.75 increase per year/1000 game-days) over time. There were significantly more games missed due to orbital fractures than games missed due to contusions/lacerations (11.5 vs. 2.8 missed games, P = 0.01). CONCLUSION: We demonstrate an increasing trend of eye injuries in the NBA, resulting in increased financial loss. Injuries may be varied in type and affect the number of games missed.

The distribution of industry payments among pediatric dermatologists from 2015 to 2021.

BACKGROUND/OBJECTIVES: To understand the landscape of industry payments to pediatric dermatologists to foster transparency and identify potential disparities in funding. METHODS: Using the Centers for Medicare and Medicaid Services (CMS) Open Payments database, a national cross-sectional study was performed examining payments to pediatric dermatologists from 2015 to 2021. RESULTS: Of the 147 pediatric dermatologists who received industry funding, 35 were male and 112 were female. $9 million in payments was amassed, with 10% of pediatric dermatologists accounting for 94% of total industry payments. Consulting was the most common service, with Pfizer Inc., Amgen Inc., and Regeneron Healthcare Solutions Inc. representing the top three companies. Mean payment was $143,836 for males and $35,943 for females (p < .001). Eight female and seven male pediatric dermatologists received payments in the top 10th percentile, with different average payment in this subgroup (females $447,588 vs. males $698,746, p = .03). 11 states did not have a pediatric dermatologist receiving industry payments, while California (19) and Texas (12) had the most. CONCLUSIONS: There are approximately 400 board-certified pediatric dermatologists in the United States and fewer than 40% are receiving monetary compensation from private industry. A fraction of physicians accounted for a majority of total industry payments and industry payments to male pediatric dermatologists were higher despite nearly triple the number of female pediatric dermatologists. With the rise of valuable partnerships between healthcare and industry in modern medicine, the implications of geographic, gender, and financial disparity of industry payments in pediatric dermatology are worthy of further study.

The top 100 most cited Mohs micrographic surgery articles: an analysis of Altmetrics data from 2010 to 2020.

With skin cancer rates rising, there is a consistent stream of literature published on Mohs micrographic surgery (MMS). However, there are no studies examining MMS article visibility and readership patterns. The Altmetric Attention Score (AAS) is a metric that quantifies article distribution on media platforms. We analyzed the 100 most cited MMS publications from 2010 to 2020 and constructed multivariate regression models using top 25th percentile AASs and mentions on Facebook, Twitter, and new outlets as outcome variables. Articles with an AAS in the top 25th quartile consistently performed better with higher citations, Twitter mentions, Facebook mentions, and journal impact factors compared to articles in the lower three quartiles (53.8 vs 33.9; 4.68 vs 0.44; 0.32 vs 0.08; 53.5 vs 14.6; p < 0.05 for all). There were significantly lower female last authors versus males in the top quartile of AAS articles, with males 142 times more likely to have articles in the top quartile (p < 0.05). Studies comparing MMS to other surgical techniques and funded articles had higher odds of being in the top quartile of AASs (aOR 29.63 p < 0.05; aOR 74.50 p < 0.05). AASs can be useful to understand public interest, readership, and article features that influence the reach of MMS literature.

Artificial Intelligence Automation of Proptosis Measurement: An Indicator for Pediatric Orbital Abscess Surgery.

INTRODUCTION: To evaluate the ability of artificial intelligence (AI) software to quantify proptosis for identifying patients who need surgical drainage. METHODS: We pursued a retrospective study including 56 subjects with a clinical diagnosis of subperiosteal orbital abscess (SPOA) secondary to sinusitis at a tertiary pediatric hospital from 2002 to 2016. AI computer software was developed to perform 3D visualization and quantitative assessment of proptosis from computed tomography (CT) images acquired at the time of hospital admission. The AI software automatically computed linear and volume metrics of proptosis to provide more practice-consistent and informative measures. Two experienced physicians independently measured proptosis using the interzygomatic line method on axial CT images. The AI software and physician proptosis assessments were evaluated for association with eventual treatment procedures as standalone markers and in combination with the standard predictors. RESULTS: To treat the SPOA, 31 of 56 (55%) children underwent surgical intervention, including 18 early surgeries (performed within 24 h of admission), and 25 (45%) were managed medically. The physician measurements of proptosis were strongly correlated (Spearman r = 0.89, 95% CI 0.82-0.93) with 95% limits of agreement of ± 1.8 mm. The AI linear measurement was on average 1.2 mm larger (p = 0.007) and only moderately correlated with the average physicians' measurements (r = 0.53, 95% CI 0.31-0.69). Increased proptosis of both AI volumetric and linear measurements were moderately predictive of surgery (AUCs of 0.79, 95% CI 0.68-0.91, and 0.78, 95% CI 0.65-0.90, respectively) with the average physician measurement being poorly to fairly predictive (AUC of 0.70, 95% CI 0.56-0.84). The AI proptosis measures were also significantly greater in the early as compared to the late surgery groups (p = 0.02, and p = 0.04, respectively). The surgical and medical groups showed a substantial difference in the abscess volume (p < 0.001). CONCLUSION: AI proptosis measures significantly differed from physician assessments and showed a good overall ability to predict the eventual treatment. The volumetric AI proptosis measurement significantly improved the ability to predict the likelihood of surgery compared to abscess volume alone. Further studies are needed to better characterize and incorporate the AI proptosis measurements for assisting in clinical decision-making.

Interface fluid syndrome after LASIK surgery: retrospective pooled analysis and systematic review.

Interface fluid syndrome (IFS) is a complication associated with laser in situ keratomileusis (LASIK) surgery where a fluid pocket in the corneal stroma decreases visual acuity. A systematic review of IFS cases using PRISMA guidelines was performed yielding a total of 33 patients. 2 outcomes were selected for logistic regression analysis: final corrected distance visual acuity (CDVA) and need for surgical management. Results showed 33.3% of patients required surgery, 51.5% had their IFS resolve within 1 month or sooner, and 51.5% had final CDVA 20/25 or better. Higher presenting intraocular pressure (IOP) and duration of IFS ≤1 month was associated with higher odds of final CDVA 20/25 or better (adjusted odds ratio [aOR] 1.12, P = .04; aOR 7.71, P = .02, respectively). Endothelial cell dysfunction led to 17.55 greater odds for requiring surgical compared to medical management (aOR 0.36, P = .04). Presenting IOP and duration of IFS predicted final CDVA, while prior endothelial cell dysfunction predicted need for surgery.

More than just a stye: identifying seasonal patterns using google trends, and a review of infodemiological literature in ophthalmology.

PURPOSE: We aim to evaluate the utility of internet search query data in ophthalmology by: (1) Evaluating trends in searches for styes in the United States and worldwide, and (2) Performing a review of literature of infodemiological data in ophthalmology. METHODS: Google Trends search data for "stye" was analyzed from January 2004 to January 2020 in the United States and worldwide. Spearman's correlation coefficient and sinusoidal modeling were performed to assess the significance and seasonality of trends. Review of literature included searches for "ophthalmology Google trends," "ophthalmology twitter trends," "ophthalmology infodemiology," "eye google trends," and "social media ophthalmology." RESULTS: Searches for styes were cyclical in the United States and globally with a steady increase from 2004 to 2020 (sum-of-squares F-test for sinusoidal model: p < .0001, r2 = 0.96). Peak search volume index (SVI) months were 7.9 months in the United States and 6.8 months worldwide. U.S. temperature and SVI for stye were correlated in the United States at the state, divisional, and country-wide levels (p < .005; p < .005; p < .01 respectively). Seven articles met our literature review inclusion criteria. CONCLUSIONS: We present a novel finding of seasonality with global and U.S. searches for stye, and association of searches with temperature in the United States. Within ophthalmology, infodemiological literature has been used to track trends and identify seasonal disease patterns, perform disease surveillance, improve resource optimization by identifying regional hotspots, tailor marketing, and monitor institutional reputation. Future research into this domain may help identify further trends, improve prevention efforts, and reduce medical costs.

Utility of diffusion-weighted imaging to differentiate benign and malignant solid orbital tumours.

OBJECTIVE: We assessed the utility of apparent diffusion coefficients (ADCs) derived from diffusion-weighted imaging to differentiate benign and malignant orbital tumours by oculoplastic surgeons in the clinical setting and sought to validate observed ADC cut-off values. DESIGN AND PARTICIPANTS: Retrospective review of patients with benign or malignant biopsy-confirmed orbital tumours. METHODS: Blinded graders including 2 oculoplastic surgeons, 1 neuroradiologist, and 1 medical student located and measured orbital tumour ADCs (10-6 mm2/s) using the Region of Interest tool. OUTCOME MEASURES: Nonradiologist measurements were compared with each other to assess reliability and with an expert neuroradiologist measurement and final pathology to assess accuracy. RESULTS: Twenty-nine orbital tumours met inclusion criteria, consisting of 6 benign tumours and 23 malignant tumours. Mean ADC values for benign orbital tumours were 1430.59 ± 254.81 and 798.68 ± 309.12 mm2/s for malignant tumours. Our calculated optimized ADC cut-off to differentiate benign from malignant orbital tumours was 1120.84 × 10-6 mm2/s (sensitivity 1, specificity 0.9). Inter-rater reliability was excellent (intraclass correlation coefficient = 0.92; 95% CI, 0.86-0.96). Our 3 graders had a combined accuracy of 84.5% (92.3%, 92.3%, and 65.4%). CONCLUSIONS: Our ADC cut-off of 1120.84 × 10-6 mm2/s for benign and malignant orbital tumours agrees with previously established values in literature. Without priming with instructions, training, or access to patient characteristics, most tumours were correctly classified using rapid ADC measurements. Surgeons without radiologic expertise can use the ADC tool to quickly risk stratify orbital tumours during clinic visits to guide patient expectations and further work-up.

Risk factors for enucleation or evisceration in endophthalmitis.

PURPOSE: To identify clinical risk factors for enucleation or evisceration in patients with endophthalmitis at an academic institution. METHODS: A retrospective review of patients diagnosed with endophthalmitis at Wilmer Eye Institute from 2010 to 2019 was conducted. Clinical characteristics, including demographics, cause for endophthalmitis, microbial culture results, salvaging procedures and surgical intervention were recorded. In patients who underwent enucleation or evisceration, type of surgery and placement of a primary implant were recorded. Chi-squared, Student's t-tests and multivariate analysis were used to identify clinical factors that predicted enucleation or evisceration. RESULTS: Two hundred and fifty three patients treated for endophthalmitis over the study period were identified, of which 25 (9.88%) underwent enucleation or evisceration. Risk factors for enucleation or evisceration included poor presenting visual acuity (OR 7.86, CI: 2.26, 27.3), high presenting intraocular pressure (OR 1.07, CI: 1.03, 1.12), presence of relative afferent pupillary defect (OR 3.69, CI: 1.20, 11.37) and positive vitreous culture for methicillin-resistant staphylococcus aureus (MRSA) (OR 18.3, CI: 1.54, 219.2) on multivariate analysis. Patients undergoing enucleation or evisceration were also more likely to have trauma, corneal ulcer or combined causes for endophthalmitis and underwent fewer salvaging surgical and procedural interventions. There were no significant differences in characteristics of those receiving enucleation versus evisceration in our cohort. CONCLUSION: Patients with endophthalmitis who underwent enucleation or evisceration had more severe disease on presentation compared to those treated with eye sparing therapy. Presenting clinical characteristics may have a role in triage and management decisions for patients presenting with severe endophthalmitis.

Association of Proton Pump Inhibitor/Histamine-2 Blocker Use and Ocular Toxoplasmosis: Findings from a Large US National Database.

OBJECTIVE: To test the hypothesis that the use of proton pump inhibitors (PPIs) is associated with an increased risk of being diagnosed with toxoplasmic retinochoroiditis. DESIGN: Retrospective, matched case-control study using data from 2000 to 2020. PARTICIPANTS: Patients with ocular toxoplasmosis and controls were matched 5:1 for age, sex, and race, with the eligibility date ± 3 months from the index date of exposed match. Patients aged < 18 years with congenital toxoplasmosis, having < 2 years in the insurance plan before the index date, and without ≥ 1 visit to an eyecare provider before the index date were excluded from the study. METHODS: Patients with ocular toxoplasmosis were identified using the International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes, and PPI use or diseases highly associated with PPIs were identified using national drug codes from an administrative medical claims database. MAIN OUTCOME MEASURES: The primary outcome was defined as having a prescription for a PPI or histamine-2 (H2) blocker. Multivariable logistic regression analyses were performed, controlling for demographic and systemic health variables. RESULTS: A total of 4069 cases and 19 177 controls met the eligibility criteria. Of the 4069 patients with ocular toxoplasmosis, 989 (24.3%) were on PPI/H2 blockers compared with 3763 of 19 177 (19.2%) controls. The adjusted logistic regression model demonstrated 1.28 greater odds of PPI/H2 blocker use in cases of ocular toxoplasmosis than matched controls (95% confidence interval, 1.17-1.40; P < 0.001). CONCLUSIONS: Proton pump inhibitor/H2 blocker exposure was associated with an increased risk of being diagnosed with ocular toxoplasmosis, corroborating findings from a prior case series. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Predictive Factors of Research Productivity among Ophthalmology Residents: A Benchmark Analysis.

Introduction Positive and negative associations between prior publications and future research productivity is described in other fields, but no such analysis exists for ophthalmology. We conducted a study to determine characteristics of residents exhibiting research productivity during residency. Methods Using San Francisco Match and Program Web sites, a roster of ophthalmology residents in 2019 to 2020 was compiled, and publication data was collected via PubMed and Google Scholar on a random sample of 100 third-year residents. Results The median number of publications generated by ophthalmology residents before residency is 2 (range 0-13). Thirty-seven, 23, and 40 residents had zero, one, and two or more papers published during residency, respectively, with a median of 1 (range 0-14). On univariate analysis, compared with residents who published zero or one paper, those who published ≥ 2 were more likely to have more preresidency publications (odds ratio [OR] 1.30; p = 0.005), attend a top-25 ranked residency program by multiple metrics including Doximity reputation (OR 4.92; p < 0.001), and have attended a top-25 ranked medical school program by U.S. News and World Report (OR 3.24; p = 0.03). However, on adjusted analyses, the only factor that remained significant for predicting publications in residency was whether the residency program attended was top 25 ranked (OR 3.54; p = 0.009). Discussion/Conclusion With the advent of the United States Medical Licensing Examination Step 1 pass/fail system, greater emphasis will be placed on other metrics, including research. This is the first benchmark analysis examining factors predictive of publication productivity in ophthalmology residents. Our study suggests that the residency program attended, not the medical school attended or prior publication history, plays an influential role in the number of publications produced during residency, highlighting the importance of factors to support research on the institutional level, such as mentorship and funding, rather than historical factors in research productivity by the resident.

Neuroimaging Correlates of Syndromal Anxiety Following Traumatic Brain Injury: A Systematic Review of the Literature.

BACKGROUND: Traumatic brain injury (TBI) can precipitate new-onset psychiatric symptoms or worsen existing psychiatric conditions. To elucidate specific mechanisms for this interaction, neuroimaging is often used to study both psychiatric conditions and TBI. This systematic review aims to synthesize the existing literature of neuroimaging findings among patients with anxiety after TBI. METHODS: We conducted a Preferred Reporting Items for Systematic Review and Meta-Analyses-compliant literature search via PubMed (MEDLINE), PsychINFO, EMBASE, and Scopus databases before May, 2019. We included studies that clearly defined TBI, measured syndromal anxiety as a primary outcome, and statistically analyzed the relationship between neuroimaging findings and anxiety symptoms. RESULTS: A total of 5982 articles were retrieved from the systematic search, of which 65 studied anxiety and 13 met eligibility criteria. These studies were published between 2004 and 2017, collectively analyzing 764 participants comprised of 470 patients with TBI and 294 non-TBI controls. Imaging modalities used included magnetic resonance imaging, functional magnetic resonance imaging, diffusion tensor imaging, electroencephalogram, magnetic resonance spectrometry, and magnetoencephalography. Eight of 13 studies presented at least one significant finding and together reflect a complex set of changes that lead to anxiety in the setting of TBI. The left cingulate gyrus in particular was found to be significant in 2 studies using different imaging modalities. Two studies also revealed perturbances in functional connectivity within the default mode network. CONCLUSIONS: This is the first systemic review of neuroimaging changes associated with anxiety after TBI, which implicated multiple brain structures and circuits, such as the default mode network. Future research with consistent, rigorous measurements of TBI and syndromal anxiety, as well as attention to control groups, previous TBIs, and time interval between TBI and neuroimaging, are warranted. By understanding neuroimaging correlates of psychiatric symptoms, this work could inform future post-TBI screening and surveillance, preventative efforts, and early interventions to improve neuropsychiatric outcomes.

Nonmydriatic Ultra-Widefield Fundus Photography in a Hematology Clinic Shows Utility for Screening of Sickle Cell Retinopathy.

PURPOSE: To determine the feasibility and accuracy of nonmydriatic ultra-widefield (UWF) fundus photographs taken in a hematology clinic setting for screening of sickle cell retinopathy (SCR) DESIGN: Prospective cohort study. METHODS: This single-site study took place at the Johns Hopkins Sickle Cell Center for Adults and the Wilmer Eye Institute. The study population was 90 eyes of 46 consecutive adults with sickle cell disease (SCD). Bilateral nonmydriatic fundus photos taken by clinic personnel during the participants' routine hematology appointment were graded by 2 masked retina specialists at the Wilmer Eye Institute for the presence of nonproliferative SCR (NPSR) and proliferative sickle retinopathy (PSR). A third retina specialist adjudicated in cases of grader disagreement. All participants underwent the standard dilated fundus examination (DFE) within 2 years of acquisition of UWF photographs. The main outcome measure was the sensitivity and specificity of nonmydriatic UWF images for the detection of NPSR and PSR RESULTS: PSR was noted in 19 of 90 eyes that underwent DFE and in 9 of 67 gradable UWF images. Interrater agreement between the 2 graders was moderate, with κ = 0.65 (range 0.43-0.87) for PSR. For gradable UWF photos, the sensitivity and specificity of detecting SCR using the nonmydriatic photos compared with the DFE were 85.2% and 62.5% for NPSR, respectively, and 69.2% and 100% for detection of PSR, respectively. One participant required ophthalmic therapy in both eyes for active sea-fan neovascularization. CONCLUSIONS: UWF imaging shows utility in screening for SCR and may help identify patients with PSR who require a DFE and who may benefit from treatment.

Adequacy of samples obtained via percutaneous core-needle rebiopsy for EGFR T790M molecular analysis in patients with non-small cell lung cancer following acquired resistance to first-line therapy: A systematic review and meta-analysis.

MICRO ABSTRACT: Rebiopsies characterizing resistance mutations in patients with non-small cell lung cancer (NSCLC) can guide personalized medicine and improve overall survival rates. In this systematic review, we examine the suitability of percutaneous core-needle biopsy (PT-CNB) to obtain adequate samples for molecular characterization of the acquired resistance mutation T790M. This review provides evidence that PT-CNB can obtain samples with high adequacy, with a mutation detection rate that is in accordance with prior literature. BACKGROUND: Non-small cell lung cancer (NSCLC) comprises 85% of all lung cancers and has seen improved survival rates with the rise of personalized medicine. Resistance mutations to first-line therapies, such as T790M, however, render first-line therapies ineffective. Rebiopsies characterizing resistance mutations inform therapeutic decisions, which result in prolonged survival. Given the high efficacy of percutaneous core-needle biopsy (PT-CNB), we conducted the first systematic review to analyze the ability of PT-CNB to obtain samples of high adequacy in order to characterize the acquired resistance mutation T790M in patients with NSCLC. METHODS: We performed a comprehensive literature search across PubMed, Embase, and CENTRAL. Search terms related to "NSCLC," "rebiopsy," and "PT-CNB" were used to obtain results. We included all prospective and retrospective studies that satisfied our inclusion and exclusion criteria. A random effects model was utilized to pool adequacy and detection rates of the chosen articles. We performed a systematic review, meta-analysis, and meta-regression to investigate the adequacy and T790M detection rates of samples obtained via PT-CNB. RESULTS: Out of the 173 studies initially identified, 5 studies met the inclusion and exclusion criteria and were chosen for our final cohort of 436 patients for meta-analysis. The pooled adequacy rate of samples obtained via PT-CNB was 86.92% (95% CI: [79.31%, 92.0%]) and the pooled T790M detection rate was 46.0% (95% CI: [26.6%, 66.7%]). There was considerable heterogeneity among studies (I2 > 50%) in both adequacy and T790M detection rates. CONCLUSION: PT-CNB can obtain adequate samples for T790M molecular characterization in NSCLC lung cancer patients. Additional prospective studies are needed to corroborate the results in this review.