Ralph Lauren Center for Cancer Care and Prevention

ABSTRACT We document widespread changes to the historical I/B/E/S analyst stock recommendations database. Across seven I/B/E/S downloads, obtained between 2000 and 2007, we find that between 6,580 (1.6%) and 97,582 (21.7%) of matched observations are different from one download to the next. The changes include alterations of recommendations, additions and deletions of records, and removal of analyst names. These changes are nonrandom, clustering by analyst reputation, broker size and status, and recommendation boldness, and affect trading signal classifications and back‐tests of three stylized facts: profitability of trading signals, profitability of consensus recommendation changes, and persistence in individual analyst stock‐picking ability.

BACKGROUND: Patient navigation is an intervention developed to reduce disparities in cancer care that is being widely replicated and receiving considerable support for demonstration projects and research to test its effectiveness. In the current study, the authors present an in-depth descriptive analysis of the original patient navigation programs to inform current and future program development. METHODS: A qualitative multistakeholder case study using interviews and site visits of the first patient navigation site and 2 sites subsequently developed by the leadership of the original site were evaluated. RESULTS: At these sites, patient navigation is a system, as opposed to a person, comprised primarily of navigators and directors that work together to remove barriers and facilitate access in a well-defined course of care; navigators were from the community or were culturally similar to the patient population served but were also paid employees of the clinical care site with detailed knowledge of the clinical course patients must traverse to complete care plans. Directors had administrative authority over the clinical facility and social capital across institutions, and communicated regularly and openly with navigators to implement system level changes to remove barriers to care. Contextual factors such as policies supporting breast cancer care also influenced the implementation of these programs. CONCLUSIONS: The first patient navigation programs combined community and culturally sensitive care-coordination with aspects of disease management programs to reduce racial, ethnic, and poverty-driven disparities in care. Future efforts to replicate and evaluate patient navigation should take into account these unique aspects of the original patient navigation programs.

Since 1971, when President Richard Nixon declared a “War on Cancer,” profound advances in biomedical science, especially at the molecular/genetic level, have increased longevity and improved quality of life for many patients. Despite our tremendous scientific advances, some populations in this country bear a heavier burden of cancer, particularly the poor and underserved, as evidenced by their high cancer incidence, mortality, and lower survival. Over the last three decades, a number of landmark reports have been published that identify health disparities as an important national concern. Disease always occurs within a context of human circumstances including economic status, social position, culture, and environment. These human circumstances can determine length and quality of survival. The existence of health disparities poses a challenge to the scientific community and is a moral and ethical dilemma for this nation. A significant disconnect exists between what we discover and what we deliver to all people. This disconnect is, in and of itself, a cause of disparities.

Hypertension is a typical example of long-term disease posing formidable challenges to health care. One goal of antihypertensive therapy is to achieve optimal blood pressure (BP) control and reduce co-occurring chronic conditions (multimorbidity). This study aimed to assess the influence of multimorbidity on medication adherence, and to explore the association between poor BP control and multimorbidity, with implications for hypertension management.A cross-sectional design with multistage sampling was adopted to recruit Chinese hypertensive patients attending general out-patient clinics from 3 geographic regions in Hong Kong. A modified systemic sampling methodology with 1 patient as a sampling unit was used to recruit consecutive samples in each general out-patient clinic. Data were collected by face-to-face interviews using a standardized protocol. Poor BP control was defined as having systolic BP/diastolic BP ≥130/80 mm Hg for those with diabetes or chronic kidney disease; and ≥140/90 mm Hg for others. Medication adherence was assessed by a validated Chinese version of the Morisky Medication Adherence Scale. A simple unweighted enumeration was adopted to measure the combinations of coexisting long-term conditions. Binary logistic regression analysis was conducted with medication adherence and multimorbidity as outcome variables, respectively, after controlling for effects of patient-level covariates.The prevalence of multimorbidity was 47.4% (95% confidence interval [CI] 45.4%-49.4%) among a total of 2445 hypertensive patients. The proportion of subjects having 0, 1, and ≥2 additional long-term conditions was 52.6%, 29.1%, and 18.3%, respectively. The overall rate of poor adherence to medication was 46.6%, whereas the rate of suboptimal BP control was 48.7%. Albeit the influence of multimorbidity on medication adherence was not found to be statistically significant, patients with poorly controlled BP were more likely to have multimorbidity (adjusted odds ratio 2.07, 95% CI 1.70-2.53, P < 0.001). Diabetes was the most prevalent concomitant long-term condition among hypertensive patients with poor BP control (38.6%, 95% CI 35.8-41.4 vs 19.7%, 95% CI 17.5-21.9 for patients with good BP control, P < 0.001).Multimorbidity was common among hypertensive patients, and was associated with poor BP control. Subjects with coexisting diabetes, heart disease, or chronic kidney disorder should receive more clinical attention to achieve better clinical outcomes.

Quite recently, I had a personal experience that underscored why we must constantly revisit the issue of race in America. I went to the University of North Carolina at Chapel Hill in search of information about my great-great grandfather. I knew he was a slave in Raleigh, North Carolina who bought

Cardinal events in atherogenesis are the retention of apolipoprotein B-containing lipoproteins in the arterial wall and the reaction of macrophages to these particles. My laboratory has been interested in both the cell biological events producing apolipoprotein B-containing lipoproteins, as well as in the reversal of the damage they cause in the plaques formed in the arterial wall. In the 2013 George Lyman Duff Memorial Lecture, as summarized in this review, I covered 3 areas of my past, present, and future interests, namely, the regulation of hepatic very low density lipoprotein production by the degradation of apolipoprotein B100, the dynamic changes in macrophages in the regression of atherosclerosis, and the application of nanoparticles to both image and treat atherosclerotic plaques.

Testing for BRCA1 mutation has important clinical implications such as identifying risk of second primary cancers and risk of cancer in the family. This study seeks to quantify the risk of having BRCA1 mutation in female breast cancer patients with triple-negative phenotype compared with those with other phenotypes. We undertook a search of MEDLINE and EMBASE databases for relevant studies through 10 May 2013. Outcomes were calculated and reported as risk ratio and risk difference. 12 studies comprising 2533 breast cancer patients were included in the analysis. It was found that almost all eligible studies were performed on high-risk population with breast cancer. By analyzing the incidence rates of BRCA1 mutation in patients with triple-negative breast cancer (TNBC) and non-TNBC, our meta-analysis provides a relative risk of 5.65 [95% confidence interval (CI), 4.15-7.69] and risk difference of 0.22 (95% CI, 0.15-0.29). This implies that, in selected population with high-risk features, women with TNBC are approximately five and a half times more likely to have BRCA1 mutation compared with non-TNBC phenotype, and approximately two in nine women with TNBC harbor BRCA1 mutation. Triple-negative phenotype significantly increases the risk of having BRCA1 mutation in high-risk breast cancer patients compared with non-TNBC.

PURPOSE: Digital breast tomosynthesis (DBT) in conjunction with digital mammography (DM) is becoming the preferred imaging modality for breast cancer screening compared with DM alone, on the basis of improved recall rates (RR) and cancer detection rates (CDRs). The aim of this study was to investigate racial differences in the utilization and performance of screening modality. METHODS: Retrospective data from 63 US breast imaging facilities from 2015 to 2019 were reviewed. Screening outcomes were linked to cancer registries. RR, CDR per 1,000 examinations, and positive predictive value for recall (cancers/recalled patients) were compared. RESULTS: A total of 385,503 women contributed 542,945 DBT and 261,359 DM screens. A lower proportion of screenings for Black women were performed using DBT plus DM (referred to as DBT) (44% for Black, 48% for other, 63% for Asian, and 61% for White). Non-White women were less likely to undergo more than one mammographic examination. RRs were lower for DBT among all women (8.74 versus 10.06, P < .05) and lower across all races and within age categories. RRs were significantly higher for women with only one mammogram. CDRs were similar or higher in women undergoing DBT compared with DM, overall (4.73 versus 4.60, adjusted P = .0005) and by age and race. Positive predictive value for recall was greater for DBT overall (5.29 versus 4.45, adjusted P < .0001) and by age, race, and screening frequency. CONCLUSIONS: All racial groups had improved outcomes with DBT screening, but disparities were observed in DBT utilization. These data suggest that reducing inequities in DBT utilization may improve the effectiveness of breast cancer screening.

To assess the effectiveness of breast support previous studies monitored breast kinematics and kinetics, subjective feedback, muscle activity (EMG), ground reaction forces (GRFs) and physiological measures in isolation. Comparing these variables within one study will establish the key performance variables that distinguish between breast supports during activities such as running. This study investigates the effects of changes in breast support on biomechanical, physiological and subjective measures during running. Ten females (34D) ran for 10 min in high and low breast supports, and for 2 min bare breasted (2.8 m·s−1). Breast and body kinematics, EMG, expired air and heart rate were recorded. GRFs were recorded during 10 m overground runs (2.8 m·s−1) and subjective feedback obtained after each condition. Of the 62 variables measured, 22 kinematic and subjective variables were influenced by changes in breast support. Willingness to exercise, time lag and superio-inferior breast velocity were most affected. GRFs, EMG and physiological variables were unaffected by breast support changes during running. Breast displacement reduction, although previously advocated, was not the most sensitive variable to breast support changes during running. Instead breast support products should be assessed using a battery of performance indicators, including the key kinematic and subjective variables identified here.

OBJECTIVE: The objective of this study was to investigate the relationships between motor symptoms of Parkinson disease (PD) and activity limitations in persons with PD. DESIGN/METHODS: This is a cross-sectional study of persons with mild to moderate PD (N = 90). Associations among axial motor features, limb motor signs, the Physical Activity Scale for the Elderly, the ability to perform Activities of Daily Living (ADLs), and level of ADL dependency were studied. A composite score of axial motor features included the following Unified Parkinson Disease Rating Scale items: speech, rigidity of the neck, arising from chair, posture, gait, and postural stability. A composite score of limb motor signs included the following Unified Parkinson Disease Rating Scale items: tremor at rest of all extremities, action tremor, rigidity of all extremities, finger taps, hand movement, rapid alternating hand movements, and foot tapping. RESULTS: Axial motor features of PD were significantly correlated with physical inactivity (P < 0.001), decreased ADL (P < 0.001), and increase in ADL dependency (P < 0.001). Limb motor signs significantly correlated with decreased ADL (P < 0.001) and level of ADL dependency (P = 0.035) but did not correlate with physical inactivity. After controlling for age, sex, disease duration, and comorbidity, axial motor features contributed significantly to physical inactivity, decreased ADL, and increase in ADL dependency, whereas the limb motor signs did not. CONCLUSIONS: Axial motor impairment contributed to physical inactivity and decreased ability to perform ADLs in persons with PD.

The method herein presented for the separation and colorimetric determination of rhenium and molybdenum depends on differential reduction with mercury.If a dilute hydrochloric acid s olution containing molybdate and perrhenate is shaken with mercury, potassium thiocyanate, a nd ethyl ether, only the molybdenum is reduced to the form which produces an ether-soluble colored compound with thiocyanate.The color of the ether extract serves for the determination of molybdenum.Addition of stannous chloride to the a cid solution remaining after the molybdenum has been extracted produces a yellow to yellowish-red ethersoluble compound which serves for the determination of rhenium.As little as 0.001 mg of rhenium C8,n be detected in a solution containing 10 mg of molybdenum, and 0.01 mg of molybdenum can be detected in the presence of 10 mg of rhenium.Few elements interfere in the determination of rhenium, and practically all of these cnn be eliminated by a simple distillation. CONTENTS Page• Originally presented by James

During the past decade, the National Cancer Institute has made significant progress in bringing to and addressing the health and other issues related to poor and medically underserved populations, racial and ethnic minorities, and residents of rural areas. A key to the institute's achievements was the development of the Special Populations Networks (SPN) program which from 2000–2005, established a deeper involvement in reducing cancer disparities than had been previously undertaken by increasing cancer awareness and creating opportunities for conducting community-based research.

Asthma has been associated with the atherosclerosis risk, but not clear of peripheral artery disease (PAD). We attempted to examine the risk of PAD in patients with asthma.From the insurance claims data of Taiwan, we identified 28,158 newly diagnosed asthma patients in 2000 to 2005 and 56,316 persons without asthma randomly selected into the comparison cohort, frequency matched by sex, age, and the date of diagnosis. Both cohorts were followed up until the end of 2011 to estimate the incident PAD. Adjusted hazard ratios (aHRs) of PAD were estimated using the Cox proportional hazards model after controlling for sex, age, and comorbidities.The incidence of PAD was 1.46 times higher in the asthma cohort than in the comparison cohort, with an aHR of 1.34 [95% confidence interval (CI) = 1.24-1.45]. Incidence of PAD was higher in men, the aged, and those with comorbidities in both cohorts. The aHRs of PAD remained significant for the asthma cohort in all subgroups of sex, age, and the presence of comorbidity. The aHRs of PAD were 14.1 (95% CI = 8.18-24.5) in asthma patients with multiple emergency visits and 22.3 (95% CI = 15.6-31.9) for those with multiple hospitalizations.Although smoking is a potential confounding factor, this study suggests patients with asthma have a significantly higher risk of developing PAD than the general population. The results also support the notion that poor control of asthma status is a key factor in subsequent PAD development.

BACKGROUND: Colorectal cancer screening (CRCS) in the United States is inadequate in minority communities and particularly among those who lack insurance. Finding ways to increase screenings in these minorities presents a healthcare challenge. The authors sought to determine whether offering CRCS at the time of mammography is an effective way to increase CRCS among minority women. METHODS: This study was offered to women attending the Breast Examination Center of Harlem (BECH), a community outreach program of Memorial Sloan-Kettering serving the primarily black and Hispanic Harlem Community. Screening was explained, medical fitness was determined, and colonoscopies were performed. Barriers to screening and ways to overcome them were ascertained. Participants had to be at least 50 years of age without a history of colorectal cancer or screening within the last 10 years. RESULTS: There were 2616 women eligible for CRCS, of these women 2005 (77%) refused to participate in the study, and 611 (23%) women were enrolled. There was a high interest in CRCS including among those who declined to participate in the study. The major barrier was lack of medical insurance, which was partially overcome by alternative funding. Of the 611 women enrolled, 337 (55%) went on to have screening colonoscopy. Forty-nine (15%) women had adenomatous polyps. CONCLUSIONS: Offering CRCS to minority women at the time of mammography and without a physician's referral is an effective way to expand screening. Screening colonoscopy findings are similar to those in the general population. Alternatives to traditional medical insurance are needed for the uninsured.

A need exists for a breast cancer risk identification paradigm that utilizes relevant demographic, clinical, and other readily obtainable patient-specific data in order to provide individualized cancer risk assessment, direct screening efforts, and detect breast cancer at an early disease stage in historically underserved populations, such as younger women (under age 40) and minority populations, who represent a disproportionate number of military beneficiaries. Recognizing this unique need for military beneficiaries, a consensus panel was convened by the USA TATRC to review available evidence for individualized breast cancer risk assessment and screening in young (< 40), ethnically diverse women with an overall goal of improving care for military beneficiaries. In the process of review and discussion, it was determined to publish our findings as the panel believes that our recommendations have the potential to reduce health disparities in risk assessment, health promotion, disease prevention, and early cancer detection within and in other underserved populations outside of the military. This paper aims to provide clinicians with an overview of the clinical factors, evidence and recommendations that are being used to advance risk assessment and screening for breast cancer in the military.

Indonesien gilt aufgrund seiner vielen Vulkane als einer der Hotspots fur Geothermie. Doch Salz und Hitze setzen den Geothermie‐Anlagen zu und gefahrden ihre Sicherheit und Wirtschaftlichkeit. Ein Team an der BAM hat gunstigen, lokal verfugbaren Baustahl jetzt so beschichtet, dass ein nachhaltiger und sicherer Betrieb der Geothermie‐Kraftwerke moglich ist ‐ auch unter Extrembedingungen. Das BAM‐Team will das Beschichtungssystem nun den Anwendern in Indonesien zur Verfugung stellen, damit es unter Realbedingungen in einem Geothermie‐Kraftwerk getestet werden kann. Der Schutz vor Korrosion ist mitentscheidend, weil sie die Lebensdauer dieser Kraftwerke bestimmt. Unsere Arbeit konnte die Effizienz der Energieproduktion mit Geothermie wesentlich verbessern.

INTRODUCTION: Urological chronic pelvic pain syndrome (UCPPS) represents a group of pain symptoms relating to patients with pelvic pain for which treatment is largely unsatisfactory. The objective of this study is to analyze the effects of a novel treatment strategy in males suffering from UCPPS. METHODS: This retrospective, institutional review board-approved study analyzed eight male patients aged 24 to 61 with UCPPS. All the patients had a trial of antibiotic therapy, NSAIDs, and pelvic floor physical therapy before the study. The Visual Analog scale (VAS) and Functional Pelvic Pain scale (FPPS) were collected pretreatment. While continuing physical therapy, patients underwent weekly ultrasound-guided pelvic floor trigger point injections to the iliococcygeus, pubococcygeus, and puborectalis with lidocaine 1%. Concomitantly, patients received peripheral nerve hydrodissection performed on the pudendal nerve and the posterior femoral cutaneous nerve. The first two injections combined 1% lidocaine with dexamethasone, while the next four injections consisted of 1% lidocaine with traumeel (a homeopathic, plant-derived anti-inflammatory medication). At the 6-week follow-up, each patient retook the VAS and FPPS. RESULTS: The mean age of our patients was 31.8 years and the average duration of symptoms of the UCPPS was 21 months. Pretreatment, the mean VAS was 3.3 (STD 1.7) and the mean VAS posttreatment was 1.8 (STD 1.4); P < .05; 95% CI, 0.73 to 2.27. The mean FPPS pretreatment was 11.0 (STD 8.0) and the mean FPPS posttreatment was 6.3 (STD 5.3); P < .05; 95% CI, 0.03 to 9.22. CONCLUSION: Our results show promise for a novel, nonopioid-based treatment for UCPPS.

Dr McClelland: A 60-year-old man with a history of a liver transplantation 3 months earlier for hepatitis C–induced cirrhosis was transferred from an outside hospital. He reported 2 weeks of progressive visual decline in the right eye, associated with 2 months of right temporal headaches. The patient denied scalp tenderness, jaw claudication, and muscle weakness. Other significant medical history included celiac sprue, well-controlled hypertension, poorly controlled insulin-dependent diabetes mellitus, coronary artery disease, and hypercholesterolemia. The patient admitted confusion regarding his posttransplant medication regimen and recently had transferred his outpatient care from another medical facility. These factors contributed to an unintended month of 80 mg of prednisone daily following transplantation and intermittent compliance with his cyclosporine and sulfamethoxazole/trimethoprim posttransplant prophylactic agents. Cyclosporine trough levels ranged from less than 35 to 48 μg/L during the 3 weeks prior to presentation (maintenance trough levels, 100–150 μg/L). Liver function tests following the transplantation and as recently as 1 week prior to presentation revealed no evidence of rejection. Following transfer, the patient's examination revealed a visual acuity of 20/40, right eye, and 20/15, left eye. Color vision was reduced in the right eye, and there was a right relative afferent pupillary defect. Ocular motility and alignment, intraocular pressures, and external findings were normal. There was moderate optic disc swelling in the right eye without associated hemorrhage or exudate, and the left fundus was normal. Laboratory studies performed upon admission revealed mild normocytic anemia with normal white blood cell and platelet counts. An erythrocyte sedimentation rate (ESR) was 80 mm/h, and a high sensitivity C-reactive protein (CRP) was 9.2 mg/L (normal, 0–7.4 mg/L). CT of the brain was interpreted as showing no abnormalities other than mucosal thickening in the sphenoid sinus, and a diagnosis of giant cell arteritis (GCA) was considered likely. Before starting the patient on systemic corticosteroids, it was elected to perform an MRI of the brain. Dr Wolf: MRI of the brain and orbits (Fig. 1A–D) shows an expansile, contrast-enhancing process involving the right cavernous sinus and orbital apex and is contiguous with enhancing tissue along the right superolateral aspect of the sphenoid sinus. There is mass effect on the prechiasmatic optic nerve. The area of enhancement also involves the right optic canal, and there is prominence of the intraorbital optic nerve sheath complex. Finally, there is encasement of the right cavernous internal carotid artery with almost complete obliteration of the cavernous segment, confirmed by MRA, which also shows reconstitution of flow in the right internal carotid artery and branches distal to the cavernous segment (Fig. 2). On reviewing the CT, there is a bony defect near the sphenoid sinus abnormality (Fig. 3). In retrospect, subtle asymmetric fullness in the region of the right orbital apex and right cavernous sinus is apparent.FIG. 1: Precontrast (A) and postcontrast (B) T1 axial orbital MRI shows an expansile contrast-enhancing process (short thick arrow) involving the sphenoid sinus, right orbital apex, and right cavernous sinus. The right cavernous carotid artery flow void is absent (long thin arrow) with a normal flow void evident on the left (curved arrow). Precontrast (C) and postcontrast (D) T1 coronal MRI demonstrates the expansile process (short, thick arrow) involving the right superolateral aspect of the sphenoid sinus with bony destruction and extension into the right cavernous sinus. Loss of the carotid flow void is demonstrated on the right. The right optic nerve (long thin arrow) is elevated by the mass; more anterior sections (not shown) demonstrate enhancement surrounding the right optic nerve in the optic canal extending into the orbital apex. The right optic nerve is less well seen on postcontrast coronal images partly due to motion artifact.FIG. 2: MRA source image (A) at the level of the cavernous sinus mass and segmented maximum intensity projection image (B) of the right internal carotid distribution confirmed the involvement of the right cavernous internal carotid artery, with narrowing of the cavernous carotid artery resulting in loss of flow-related enhancement on the source image (short, thick arrow) and flow gap on the segmented maximum intensity projection image (long, thin arrow). There is reconstitution of flow in the right internal carotid artery distal to the involved segment. The source image shows normal flow in the left cavernous carotid artery (curved arrow).FIG. 3: Axial CT with soft tissue (A) and bone window (B) settings reveals asymmetric soft tissue prominence of the right cavernous sinus (arrow), with adjacent bony defect of the sphenoid sinus wall (arrowhead).Dr McClelland: A lumbar puncture revealed clear cerebrospinal fluid (CSF), with no cells, a normal glucose content, and a mildly elevated protein concentration of 59 mg/dL (normal, 15–45 mg/dL). Gram stain was negative as were bacterial, fungal, and acid-fast bacilli cultures. Polymerase chain reaction was negative for evidence of varicella zoster virus, cytomegalovirus, human herpes virus-6, and herpes simplex virus. Additional normal serum laboratory studies included galactomannan (Aspergillus antigen), Bartonella henselae IgG/IgM, Mycoplasma IgM, angiotensin-converting enzyme, Lyme antibody, and cryptococcal antigen. Dr Liu: In view of the neuroimaging findings in this immunocompromised patient, an otolaryngological consultation was requested. Dr Rassekh: The cranial base surgery team discussed the case and reviewed the neuroimaging studies. We agreed that endoscopic biopsy with limited debridement was appropriate but that the mass in the lateral wall of the sphenoid sinus adjacent to the right optic nerve and cavernous sinus could not be biopsied unless it could be removed with suction. Aggressive debridement would dramatically increase the risk of catastrophic hemorrhage or stroke related to injury to the cavernous internal carotid artery, visual loss due to injury to the optic nerve, and CSF rhinorrhea in the region of the cavernous sinus that could lead to intracranial infection. At surgery, the sphenoid sinus was opened and the bone of the sphenoid rostrum was removed inferiorly to reveal a whitish yellow mass that was removed and sent for pathological and microbiological analyses. In addition, there were areas of white plaque under the mucosa, most prominently found in the superolateral sphenoid sinus in the region of the opticocarotid recess. The sphenoid sinus was irrigated to remove remaining debris. Dr LiVolsi: Multiple biopsies from the sphenoid sinus show inflamed sinonasal mucosa, bone fragments, and associated necrotic material containing abundant fungal organisms (Fig. 4A) with septate hyphae morphologically suggestive of Aspergillus species (Fig. 4B). Fungal cultures of the sphenoid sinus biopsy specimen grew Aspergillus fumigatus.FIG. 4: Sphenoid sinus biopsy. A. There is inflamed mucosa (straight arrow) adjacent to a cluster of fungal organisms consistent with an aspergilloma (bent arrow) (hematoxylin and eosin, ×10). B. Abundant septate hyphae with a 45° branching pattern (red arrows) are present consistent with Aspergillus (Grocott methenamine silver stain, ×40).Final Diagnosis Right optic neuropathy due to invasive sinonasal aspergillosis with cavernous sinus and orbital apex extension. Dr Blumberg: Prior to the biopsy, the patient had been placed on both antibacterial and antiviral agents. In view of the biopsy findings suggestive of Aspergillus species, the patient was started immediately on intravenous amphotericin with cessation of other antimicrobial agents. The clinical picture was further complicated by acute elevation of liver function tests. A transjugular core biopsy of the liver demonstrated acute cellular rejection without evidence of infection. The diagnosis of acute hepatic rejection mandated urgent steroid therapy, placing the patient in a precarious and grave balancing act between suppressing immunity to prevent liver failure and bolstering immunity to prevent progression of Aspergillus. The chronic and serious nature of both issues denoted a very poor prognosis for this patient if treated medically. Given the angioinvasive nature of Aspergillus and the patient's obligatory future immunosuppression, it was thought that the best chance for recovery was aggressive surgical debridement. The neurosurgery and otolaryngology services were asked to consider a right orbital exenteration with extensive debridement of the sphenoid sinuses and right orbital apex/cavernous sinus region. Dr Grady: The surgical treatment for this patient's infection would require a radical resection, including right orbital exenteration, resection of the right cavernous sinus and its contents, and occlusion of the right carotid artery. A tissue graft then would be required to fill the defect and close off the communication between the CSF-filled intracranial cavity and the paranasal sinuses. Given the region of pathology in the cavernous sinus and orbital apex, the angioinvasive tendencies of Aspergillus, and the coagulopathy inherent with liver failure, the risk of stroke and life-threatening hemorrhage in this patient was thought to be considerable. In addition, surgical debridement would be incomplete, given the extensive nature of fungal invasion. Based on these factors, the neurosurgical service declined to perform surgery and instead recommended continuation of medical management. The patient's medication was subsequently changed from amphotericin to voriconazole and caspofungin. Six months following presentation, the patient remains alive on long-term caspofungin and voriconazole, although his condition has progressively worsened. Vision in the right eye declined to no light perception. His last MRI showed mild interval progression in the size of the right orbital apex and cavernous sinus mass. Despite immunosuppression with tacrolimus, his liver continues to fail, leading to massive ascites. The patient has sought second opinions from 4 other academic centers, and all have declined additional surgery due to a consensus that his disease is inoperable. Dr McClelland and Dr Liu: Giant cell arteritis is a relatively common cause of acute-onset catastrophic vision loss in the elderly (1). Prevention of progression to bilateral blindness from GCA relies on clinicians maintaining a high-index of suspicion and initiating early steroid therapy. This case highlights that caution must be exercised when considering steroid therapy for possible giant cell arteritis, particularly in patients with known immunosuppression, and that an elevated ESR and CRP, although consistent with GCA, also occur in patients with other infectious disorders, including fungal infections. Seton et al (2) reported a similar case of invasive sinonasal Aspergillus mimicking GCA in an immunosuppressed 68-year-old man, 3.5 months after a liver transplant for liver failure from hepatitis C. Their patient presented with vision loss in the right eye, fundus findings “consistent with anterior ischemic optic neuropathy,” new right temporal headaches with scalp tenderness, and jaw fatigue. He was placed on high-dose prednisone for 3 weeks before the infection progressed, ultimately succumbing to a ruptured mycotic basilar artery aneurysm. The rheumatologic literature reports a 93.5% sensitivity and 91.2% specificity for GCA when 3 of the following 5 criteria are met: age being 50 years or older, new onset of localized headache, temporal artery tenderness or decreased temporal artery pulse, elevated ESR ≥50 mm/h, and a temporal artery biopsy indicative of GCA (3). Cases such as ours suggest that these guidelines may not apply to immunocompromised patients in whom GCA is exceedingly rare and elevated acute phase reactants, such as ESR and CRP, are more likely to reflect an underlying infectious process. Aspergillus fumigatus, along with other less common Aspergillus species, are molds that are ubiquitous in the environment (4). Fungal spores are typically inhaled by humans into the sinonasal and pulmonary airways but rarely cause symptomatic infection in immunocompetent individuals. When disease occurs, it can affect virtually any organ system, although the lungs, sinuses, brain, and skin are the most commonly involved (4). Sinonasal involvement by Aspergillus may result in diverse and overlapping clinical findings, including benign colonization, allergic fungal sinusitis (AFS), sinus mycetoma (or “fungus ball”), chronic invasive fungal sinusitis, and acute fulminant invasive sinusitis. These disease patterns are not specific to Aspergillus and are seen with numerous other fungi (5). The form and severity of pathology in any given case likely reflects the effectiveness of the host immune response. AFS is the most common form of fungal rhinosinusitis constituting approximately 7% of all chronic rhinosinusitis requiring surgery (6,7). AFS is characterized by noninvasive chronic infection of the paranasal sinuses in immunocompetent patients associated with copious allergic mucin (5). Sinus mycetoma is another noninvasive form of fungal rhinosinusitis generally involving one sinus and characterized histopathologically by a matted “ball” of inflammation and fungal hyphae (8). In both forms of noninvasive fungal sinonasal infection (AFS and mycetoma), the related symptoms are typical of chronic rhinosinusitis (e.g., nasal obstruction, purulent discharge, facial pain), but neuro-ophthalmic complications are rare. Our patient's subacute onset, progressive optic neuropathy, and neuroimaging evidence of invasion into the cavernous sinus through the wall of the sphenoid sinus made the diagnosis of invasive fungal rhinosinusitis evident. Invasive fungal rhinosinusitis can present in a fulminant or insidious fashion and is usually associated with aspergillosis or mucormycosis (5). Invasive Aspergillus can infect any paranasal sinus although the maxillary, ethmoid, and sphenoid sinuses are the most commonly affected (9). Cerebral aspergillosis occurs in 10%–20% of all invasive aspergillosis cases and may arise hematogenously or extend directly from the paranasal sinuses as in our case (9). Initially, invasive sinonasal and cerebral aspergillosis were documented in immunocompromised patients, but reports among immunocompetent patients are becoming more common (10,11). Definitive diagnosis of sinonasal and cerebral aspergillosis can be challenging. CSF examination is rarely helpful in diagnosis (4). Serum Aspergillus antigen (galactomannan) may be suggestive of the diagnosis, with an estimated sensitivity and specificity of 71% and 89%, respectively (12). Considering false-negative galactomannan results in biopsy-proven invasive aspergillosis, as occurred in our case, and false-positive results from cross-reactivity with other fungi or beta-lactam antibiotics (4), definitive diagnosis requires biopsy and/or culture of affected tissue (13). Optimal treatment for invasive sinonasal and cerebral Aspergillus remains controversial and is limited by a lack of prospective trials comparing treatment options. Historically, treatment consists of antifungal pharmacotherapy with aggressive surgical debridement of affected tissue (13–16). Proponents of extensive debridement consider Aspergillus an “infectious cancer” that must be excised (14). Some theorize that hypoxic tissue necrosis surrounding the angioinvasive Aspergillus promotes further growth of the fungus and prevents effective tissue penetration by antifungal agents. The risk and morbidity associated with surgical debridement has been justified by the grim prognosis in these cases. In the literature published prior to the development and widespread utilization of newer antifungal agents, invasive sinonasal aspergillosis without intracranial involvement had a 66% mortality rate (17) and cerebral aspergillosis an 88%–100% mortality rate (17–19). Since the advent of alternative antifungal agents to amphotericin (e.g., voriconazole, caspofungin, itraconazole), some clinicians have reported improved outcomes with medical management of invasive Aspergillus although early recognition of the infection is critical for treatment success (15,20–22). Panda et al (15) reported a 100% survival rate with 20–47 months of follow-up in a series of 6 immunocompetent patients with invasive aspergillosis, resulting in orbital and/or intracranial extension. All patients were treated medically with a combination of itraconazole and amphotericin B. Surgical intervention was required in only one patient; an orbital mass excision with paranasal sinus debridement was curative. It remains unclear which patients may be successfully managed by a medical approach alone and whether combination antifungal therapy may be beneficial in patients with invasive sinonasal and cerebral Aspergillus. The low prevalence of the disease hinders quality prospective trials while the wide variability of infection location, treatment regimens, and patients' immune status make retrospective studies difficult to interpret. Scarce existing data on the use of combination antifungal therapy reveal conflicting results, and there is no clear guidance regarding the use of combination therapy for solid organ transplant recipients with invasive rhinocerebral aspergillosis (23). ACKNOWLEDGMENTS The authors thank Roger Selouan, MD, for his assistance with radiographic interpretation and Kenneth S. Shindler, MD, PhD, for his assistance with photographing biopsy specimens.

OBJECTIVE: Culturally targeted narrative education is a promising approach to cancer prevention and control. This study evaluates the uptake of genetic counseling and testing (GCT) in Latinas at risk for hereditary breast and ovarian cancers (HBOC) after watching a culturally targeted narrative video and being navigated to GCT services. METHODS: Latina women at increased risk for HBOC were recruited through community-based organizations. Participants responded to surveys before and after watching Spanish-language telenovela-style video. Surveys measured sociodemographic and clinical variables, HBOC and GCT knowledge, transportation with the story, identification with characters, and emotions elicited by the video. After watching video, participants were offered patient navigation services to free or low-cost GCT and completed a 3-month follow-up phone survey to assess GCT uptake. RESULTS: Participants (N = 40) were 47.35 years old on average (SD = 9.48); all were born outside the United States. At the 3-month follow-up (N = 37), 27 (72.9%) and 26 (70.27%) participants had attended genetic counseling and genetic testing, respectively. U Mann Whitney tests found statistically significant differences between women who attended counseling versus those who did not at baseline knowledge (U = 216.00, p = 0.000) and distress elicited by the video (U = 73.5, p = 0.03). A logistic regression with distress elicited by the video as a predictive variable reached statististical significance (β = -0.27, p = 0.037, CI 95% 0.58-0.98). CONCLUSIONS: GCT uptake was promising, supporting a role for culturally targeted narrative video education along with a patient navigation component in increasing interest in cancer prevention and reducing healthcare disparities in HBOC genetic services. TRIAL REGISTRATION: NCT03075540 (Initial release 2/22/2017).

Spinal muscular atrophy (SMA) type 4 is a rare, adult-onset motor neuron disorder characterized by slowly progressive proximal weakness with preserved ambulation. Its indolent clinical course and nonspecific early manifestations frequently result in prolonged diagnostic delays. We present the complete diagnostic evaluation of a 33-year-old male patient with a multi-year history of painless, progressive lower extremity weakness. Initial laboratory testing revealed an isolated elevation of creatine kinase (CK) and vitamin D deficiency, with otherwise normal metabolic, endocrine, and inflammatory studies. Persistent CK elevation despite vitamin repletion prompted a neuromuscular referral. Electrodiagnostic testing demonstrated normal nerve conduction studies with electromyographic evidence of widespread chronic active denervation and, critically, normal paraspinal musculature. This pattern strongly supported the localization of the pathology to the anterior horn cells. Subsequent genetic testing confirmed a homozygous deletion of exon 7 in the SMN1 gene, establishing the definitive diagnosis of SMA type 4. This case underscores the importance of a systematic diagnostic approach integrating serial CK monitoring, electrodiagnostic localization, and genetic confirmation in evaluating adult-onset proximal weakness, particularly in the current era of disease-modifying therapies.