Cassie A. Ludwig

Acute Lung Injury in Patients with Subarachnoid Hemorrhage: A Nationwide Inpatient Sample Study

OBJECTIVE To determine national trends for patients with subarachnoid hemorrhage (SAH) and pulmonary complications including acute respiratory distress syndrome (ARDS). METHODS The Nationwide Inpatient Sample database was used to sample 193,209 admissions for SAH with and without ARDS during the period 1993-2008 using International Classification of Diseases, Ninth Revision, Clinical Modification coding. A multivariate stepwise regression analysis was performed. RESULTS The incidence of ARDS in patients with SAH increased from 35.51% in 1993 to 37.60% in 2008. However, the overall mortality in patients with SAH and in patients with SAH and ARDS decreased in the same period, from 42.30% to 31.99% and from 75.13% to 60.76%, respectively. Multivariate analysis showed that the predictors of developing ARDS in patients with SAH include older age; larger hospital size; and comorbidities such as epilepsy, cardiac arrest, sepsis, congestive heart failure, hypertension, chronic obstructive pulmonary disease, hematologic dysfunction, renal dysfunction, and neurologic dysfunction. Predictors of mortality in patients with SAH include age and hospital complications, such as coronary artery disease, ARDS, cancer, hematologic dysfunction, and renal dysfunction. CONCLUSIONS Patients with SAH are at increased risk of developing ARDS. The identification of certain risk factors may alert and aid practitioners in preventing worsening disease.

Ultrastructure and Innervation of Thumb Carpometacarpal Ligaments in Surgical Patients With Osteoarthritis

BackgroundThe complex configuration of the thumb carpometacarpal (CMC-1) joint relies on musculotendinous and ligamentous support for precise circumduction. Ligament innervation contributes to joint stability and proprioception. Evidence suggests abnormal ligament innervation is associated with osteoarthritis (OA) in large joints; however, little is known about CMC-1 ligament innervation characteristics in patients with OA. We studied the dorsal radial ligament (DRL) and the anterior oblique ligament (AOL), ligaments with a reported divergent presence of mechanoreceptors in nonosteoarthritic joints.Questions/purposesThis study’s purposes were (1) to examine the ultrastructural architecture of CMC-1 ligaments in surgical patients with OA; (2) to describe innervation, specifically looking at mechanoreceptors, of these ligaments using immunohistochemical techniques and compare the AOL and DRL in terms of innervation; and (3) to determine whether there is a correlation between age and mechanoreceptor density.MethodsThe AOL and DRL were harvested from 11 patients with OA during trapeziectomy (10 women, one man; mean age, 67 years). The 22 ligaments were sectioned in paraffin and analyzed using immunoflourescent triple staining microscopy.ResultsIn contrast to the organized collagen bundles of the DRL, the AOL appeared to be composed of disorganized connective tissue with few collagen fibers and little innervation. Mechanoreceptors were identified in CMC-1 ligaments of all patients with OA. The DRL was significantly more innervated than the AOL. There was no significant correlation between innervation of the DRL and AOL and patient age.ConclusionsThe dense collagen structure and rich innervation of the DRL in patients with OA suggest that the DRL has an important proprioceptive and stabilizing role.Clinical RelevanceLigament innervation may correlate with proprioceptive and neuromuscular changes in OA pathophysiology and consequently support further investigation of innervation in disease prevention and treatment strategies.

Retinal and Optic Nerve Hemorrhages in the Newborn Infant: One-Year Results of the Newborn Eye Screen Test Study

PURPOSE To report the birth prevalence, risk factors, characteristics, and location of fundus hemorrhages (FHs) of the retina and optic nerve present in newborns at birth. DESIGN Prospective cohort study at Stanford University School of Medicine. PARTICIPANTS All infants who were 37 weeks postmenstrual age or older and stable were eligible for screening. Infants with known or suspected infectious conjunctivitis were excluded. METHODS Infants born at Lucile Packard Childrens Hospital (LPCH) from July 25, 2013, through July 25, 2014, were offered universal newborn screening via wide-angle digital retinal photography in the Newborn Eye Screen Test study. Maternal, obstetric, and neonatal factors were obtained from hospital records. The location, retinal layer, and laterality of FH were recorded by 1 pediatric vitreoretinal specialist. MAIN OUTCOME MEASURES Birth prevalence of FH. Secondary outcomes included rate of adverse events, risk factors for FH, hemorrhage characteristics, and adverse events. RESULTS The birth prevalence of FH in this study was 20.3% (41/202 infants). Ninety-five percent of FHs involved the periphery, 83% involved the macula, and 71% involved multiple layers of the retina. The fovea was involved in 15% of FH cases (birth prevalence, 3.0%). No cases of bilateral foveal hemorrhage were found. Fundus hemorrhages were more common in the left eye than the right. Fundus hemorrhages were most commonly optic nerve flame hemorrhages (48%) and white-centered retinal hemorrhages (30%). Retinal hemorrhages were found most frequently in all 4 quadrants (35%) and more often were multiple than solitary. Macular hemorrhages most often were intraretinal (40%). Among the risk factors examined in this study, vaginal delivery compared with cesarean section (odds ratio [OR], 9.34; 95% confidence interval [CI], 2.57-33.97) showed the greatest level of association with FH. Self-identified ethnicity as Hispanic or Latino showed a protective effect (OR, 0.43; 95% CI, 0.20-0.94). Other study factors were not significant. CONCLUSIONS Fundus hemorrhages are common among newborns. They often involve multiple areas and layers of the retina. Vaginal delivery was associated with a significantly increased risk of FH, whereas self-identified Hispanic or Latino ethnicity was protective against FH in this study. The long-term consequences of FH on visual development remain unknown.

A novel smartphone ophthalmic imaging adapter: User feasibility studies in Hyderabad, India.

Aim of Study: To evaluate the ability of ancillary health staff to use a novel smartphone imaging adapter system (EyeGo, now known as Paxos Scope) to capture images of sufficient quality to exclude emergent eye findings. Secondary aims were to assess user and patient experiences during image acquisition, interuser reproducibility, and subjective image quality. Materials and Methods: The system captures images using a macro lens and an indirect ophthalmoscopy lens coupled with an iPhone 5S. We conducted a prospective cohort study of 229 consecutive patients presenting to L. V. Prasad Eye Institute, Hyderabad, India. Primary outcome measure was mean photographic quality (FOTO-ED study 1–5 scale, 5 best). 210 patients and eight users completed surveys assessing comfort and ease of use. For 46 patients, two users imaged the same patients eyes sequentially. For 182 patients, photos taken with the EyeGo system were compared to images taken by existing clinic cameras: a BX 900 slit-lamp with a Canon EOS 40D Digital Camera and an FF 450 plus Fundus Camera with VISUPAC™ Digital Imaging System. Images were graded post hoc by a reviewer blinded to diagnosis. Results: Nine users acquired 719 useable images and 253 videos of 229 patients. Mean image quality was ≥ 4.0/5.0 (able to exclude subtle findings) for all users. 8/8 users and 189/210 patients surveyed were comfortable with the EyeGo device on a 5-point Likert scale. For 21 patients imaged with the anterior adapter by two users, a weighted κ of 0.597 (95% confidence interval: 0.389–0.806) indicated moderate reproducibility. High level of agreement between EyeGo and existing clinic cameras (92.6% anterior, 84.4% posterior) was found. Conclusion: The novel, ophthalmic imaging system is easily learned by ancillary eye care providers, well tolerated by patients, and captures high-quality images of eye findings.

Altered Innervation Pattern in Ligaments of Patients with Basal Thumb Arthritis.

Purpose The population of mechanoreceptors in patients with osteoarthritis (OA) lacks detailed characterization. In this study, we examined the distribution and type of mechanoreceptors of two principal ligaments in surgical subjects with OA of the first carpometacarpal joint (CMC1). Methods We harvested two ligaments from the CMC1 of eleven subjects undergoing complete trapeziectomy and suspension arthroplasty: the anterior oblique (AOL) and dorsal radial ligament (DRL). Ligaments were divided into proximal and distal portions, paraffin-sectioned, and analyzed using immunoflourescent triple staining microscopy. We performed statistical analyses using the Wilcoxon Rank Sum test and ANOVA with post-hoc Bonferroni and Tamhane adjustments. Results The most prevalent nerve endings in the AOL and DRL of subjects with OA were unclassifiable mechanoreceptors, which do not currently fit into a defined morphological scheme. These were found in 11/11 (100%) DRLs and 7/11 (63.6%) AOLs. No significant difference existed with respect to location within the ligament (proximal versus distal) of mechanoreceptors in OA subjects. Conclusion The distribution and type of mechanoreceptors in cadavers with no to mild OA differ from those in surgical patients with OA. Where Ruffini endings predominate in cadavers with no to mild OA, unclassifiable corpuscles predominate in surgical patients with OA. These findings suggest an alteration of the mechanoreceptor population and distribution that accompanies the development of OA. Clinical Relevance Identification of a unique type and distribution of mechanoreceptors in the CMC1 of symptomatic subjects provides preliminary evidence of altered proprioception in OA.

Idiopathic pigmented vitreous cyst

4% use poppers. In the homosexual community, about two per cent of the population, 30% take poppers and 6% are HIV positive (Swearingen & Klausner 2005). Hence, an additional factor like the concentration of cGMP may be the key substance damaging the photoreceptor cells in poppersassociated maculopathy. Upon oxidation, alkyl nitrites give rise to nitric oxide (NO). NO stimulates guanylate cyclase which converts guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP). Guanylate cyclase (GC) is found in the cell body of the photoreceptor cell, that is the retinal cones (Ferrendelli & De Vries 1983). cGMP is an important substance in the photo-transduction cascade which allows Ca and Na to enter the cell, causing depolarization of the cell. However, very high levels of calcium will damage the photoreceptor cell (Sharma & Rohrer 2007). When patients are infected with human immunodeficiency virus (HIV), their cytokines IL-1, IL-6, interferon-gamma and TNF-alpha will increase. These cytokines activate inducible nitric oxide synthase 2 (iNOS-2), which has been shown to increase the level of NO and cGMP in the retina. In the present series, one patient was treated with a proteinase inhibitor. Proteinase inhibitors inhibit cytochrome P450 3a4. As sildenafil is broken down by cytochrome P450 3a4, proteinase inhibitors will cause an increased and prolonged concentration of sildenafil in the blood of patients using sildenafil. This indicates that also treatment of HIV patients with proteinase inhibitors might add to the development of a poppers-associated maculopathy. The three patients who were HIV negative used sildenafil besides poppers. One patient used poppers frequently for years, without any visual problems. But when he first used a combination of sildenafil and poppers, he noticed a sudden decline in visual acuity. Sildenafil, a phosphodiesterase inhibitor, prevents the degradation of cGMP. Phosphodiesterase VI is a component of the phototransduction cascade of the photoreceptor cells. So inhibition of phosphodiesterase VI, as can be seen after the use of sildenafil, causes an increased concentration of cGMP in the photoreceptor cells. Inhibition of phosphodiesterase IV was found to induce an accumulation of cGMP with degeneration of cones in pigs (Mart ınezFern andez de la C amara et al. 2013). So, sildenafil, HIV and/or proteinase inhibitors influence a common pathway through which a rise in cGMP is induced and may thus increase the risk of developing a poppers-associated maculopathy.

Traumatic epistaxis: Skull base defects, intracranial complications and neurosurgical considerations

INTRODUCTION Endonasal procedures may be necessary during management of craniofacial trauma. When a skull base fracture is present, these procedures carry a high risk of violating the cranial vault and causing brain injury or central nervous system infection. PRESENTATION OF CASE A 52-year-old bicyclist was hit by an automobile at high speed. He sustained extensive maxillofacial fractures, including frontal and sphenoid sinus fractures (Fig. 1). He presented to the emergency room with brisk nasopharyngeal hemorrhage, and was intubated for airway protection. He underwent emergent stabilization of his nasal epistaxis by placement of a Foley catheter in his left nare and tamponade with the Foley balloon. A six-vessel angiogram showed no evidence of arterial dissection or laceration. Imaging revealed inadvertent insertion of the Foley catheter and deployment of the balloon in the frontal lobe (Fig. 2). The balloon was subsequently deflated and the Foley catheter removed. The patient underwent bifrontal craniotomy for dural repair of CSF leak. He also had placement of a ventriculoperitoneal shunt for development of post-traumatic hydrocephalus. Although the hospital course was a prolonged one, he did make a good neurological recovery. DISCUSSION The authors review the literature involving violation of the intracranial compartment with medical devices in the settings of craniofacial trauma. CONCLUSION Caution should be exercised while performing any endonasal procedure in the settings of trauma where disruption of the anterior cranial base is possible.

Training time and quality of smartphone-based anterior segment screening in rural India

Objective We aimed at evaluating the ability of individuals without ophthalmologic training to quickly capture high-quality images of the cornea by using a smartphone and low-cost anterior segment imaging adapter (the “EyeGo” prototype). Methods Seven volunteers photographed 1,502 anterior segments from 751 high school students in Varni, India, by using an iPhone 5S with an attached EyeGo adapter. Primary outcome measures were median photograph quality of the cornea and anterior segment of the eye (validated Fundus Photography vs Ophthalmoscopy Trial Outcomes in the Emergency Department [FOTO-ED] study; 1–5 scale; 5, best) and the time required to take each photograph. Volunteers were surveyed on their familiarity with using a smartphone (1–5 scale; 5, very comfortable) and comfort in assessing problems with the eye (1–5 scale; 5, very comfortable). Binomial logistic regression was performed using image quality (low quality: <4; high quality: ≥4) as the dependent variable and age, comfort using a smartphone, and comfort in assessing problems with the eye as independent variables. Results Six of the seven volunteers captured high-quality (median ≥4/5) images with a median time of ≤25 seconds per eye for all the eyes screened. Four of the seven volunteers demonstrated significant reductions in time to acquire photographs (P1=0.01, P5=0.01, P6=0.01, and P7=0.01), and three of the seven volunteers demonstrated significant improvements in the quality of photographs between the first 100 and last 100 eyes screened (P1<0.001, P2<0.001, and P6<0.01). Self-reported comfort using a smartphone (odds ratio [OR] =1.25; 95% CI =1.13 to 1.39) and self-reported comfort diagnosing eye conditions (OR =1.17; 95% CI =1.07 to 1.29) were significantly associated with an ability to take a high-quality image (≥4/5). There was a nonsignificant association between younger age and ability to take a high-quality image. Conclusion Individuals without ophthalmic training were able to quickly capture a high-quality magnified view of the anterior segment of the eye by using a smartphone with an attached imaging adapter.

Validity of the Red Reflex Exam in the Newborn Eye Screening Test Cohort

BACKGROUND AND OBJECTIVE The validity of the red reflex exam has yet to be tested against new methods of wide-angle imaging that may improve early detection of neonatal ocular pathology. The authors aimed to determine the validity of the pediatricians red reflex exam using 130° wide-angle external and fundus digital imaging as a gold standard. PATIENTS AND METHODS This was a prospective cohort study of 194 healthy, term newborns enrolled in the Newborn Eye Screening Test study at Lucile Packard Childrens Hospital from July 25, 2013, to July 25, 2014. Red reflex screening was performed by a pediatrician in the newborn nursery and wide-angle fundus digital imaging was performed by a neonatal intensive care unit-certified nurse. The main outcome measure was the validity of the pediatricians red reflex exam (unweighted kappa [κ] statistic, sensitivity, specificity). RESULTS Compared to no subjects with abnormal red reflex exams reported in the pediatricians notes, 49 subjects demonstrated one or multiple ocular abnormalities on 130° wide-angle fundus imaging (κ = 0.00). The pediatricians red reflex exam had a sensitivity of 0.0% (95% CI, 0.0%-7.3%) and specificity of 100.0% (95% CI, 97.5%-100.0%) for the detection of ocular abnormalities. CONCLUSION This study demonstrates the ability of wide-angle fundus imaging to detect fundus abnormalities not otherwise identified by standard newborn red reflex screening prior to hospital discharge. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:103-110.].

The effect of statin exposure on choroidal neovascularization in nonexudative age-related macular degeneration patients

Age-related macular degeneration (AMD) is the leading cause of blindness above age 65 in industrialized countries [1]. While early-stage (nonexudative) AMD is characterized by drusenoid deposits that typically do not affect vision, late-stage AMD consists of geographic atrophy (GA) or choroidal neovascularization (CNV, also known as exudative AMD) which can cause significant vision loss. While antioxidant AREDS vitamins are currently most commonly prescribed for nonexudative AMD, no standard treatment has been established [2]. However, AMD shares several risk factors with atherosclerosis and may have similar pathophysiology [1]. Therefore, statins (β-hydroxy β-methylglutaryl-CoA [HMG-CoA] reductase inhibitors) have been hypothesized as a potential treatment. Research thus far on this topic has been contradictory. CNV in particular is not well understood with fewer relevant trials and observational studies [3, 4]. In a recent prospective cohort of 26 patients on high-dose atorvastatin (80 mg), 10 showed drusen regression, while none progressed to CNV [4]. Large-scale retrospective studies are needed to investigate this further, a gap our study addresses. Using the Stanford University Medical Center (SUMC) Clinical Data Warehouse, we performed a crosssectional study of patients with nonexudative AMD seen at SUMC since 2008. Subjects were identified using ICD9/ICD-10 codes 362.51/H35.31. The influence of statin exposure and covariates age, gender, race, and presence of comorbidities (ICD-9/ICD-10 codes for hypercholesterolemia, hypertension, cardiovascular disease, or cerebrovascular disease) on development of CNV (ICD-9/ ICD-10 362.52/H35.32) were examined using crude bivariate analyses (chi-squared) and multivariate logistic regression. Statistical assumptions were met. The protocol was approved by the Stanford University Institutional Review Board. The study population included 3090 patients (Table 1). Approximately half (49.7%) were on statins and 26.3% developed CNV. Those on statins tended to be older (67.8% ≥80), White (77.5%), and have more comorbidities (84.4%). A larger proportion of statin users developed CNV (29.3%) compared to non-statin users (23.3%). Multivariate logistic regression analysis adjusting for age, sex, race, and comorbidity status revealed statin users have increased odds of CNV (OR 1.27, CI 1.06–1.51) (Table 2). Subjects aged ≥80 (OR 2.82, CI 2.32–3.44) and White (Reference NonWhite: OR 0.50, CI 0.40–0.61) were also more likely to develop CNV after controlling for covariates. Interestingly, comorbidity effects disappeared after multivariate adjustment (OR 1.02, CI 0.84–1.25). This cross-sectional study adds to the growing literature around the therapeutic potential of statins in preventing AMD progression. Advanced AMD prevalence estimates for GA vs. CNV range from 1:1 to 2:1; however, GA currently has no treatment [5]. As suggested by Miller et al. statins may allow for drusen regression potentially circumventing GA [4]. Therefore, if statins are associated with CNV as indicated in our study, this is a small exchange given vision can be well preserved in these patients with existing therapies like anti-VEGF (vascular endothelial growth factor) [1]. Our study is a preliminary exploration of statin effect on CNV. The observed association is likely complicated by treatment and risk factors unavailable in our database and could be subject to residual confounding. Large cohort studies and randomized controlled trials incorporating risk and treatment factors (dose, class, course length, hydrophilicity) are necessary [4]. In conclusion, given the global disease burden and grave implications of advanced AMD, novel treatment with statins deserves further study and consideration. * Darius M. Moshfeghi dariusm@stanford.edu