Dilute Intralesional 5-Fluorouracil for the Treatment of Squamous Cell Carcinomas and Keratoacanthomas: A Case Series.

BACKGROUND: Intralesional 5-fluorouracil (5-FU) is a promising, yet sparsely studied alternative to surgical treatment for nonmelanoma skin cancer (NMSC).1 Previous studies of intralesional 5-FU have reported concentrations ranging from 30 to 50 mg/mL. To the best of our knowledge, this case series represents the first reported use of intralesional 5-FU 10.0 mg/mL and 16.7 mg/mL for NMSC. METHODS: A retrospective chart review identified 11 patients who received intralesional 5-FU 10.0 mg/mL and 16.7 mg/mL for 40 cutaneous squamous cell carcinomas and 10 keratoacanthomas. We describe the characteristics of these patients and calculate the clinical clearance rate of dilute intralesional 5-FU therapy for NMSC at our institution. RESULTS: Dilute intralesional 5-FU successfully treated 96% (48/50) of the study lesions, providing complete clinical clearance in 82% (9/11) of patients across a mean follow-up time of 21.7 months. All patients tolerated their treatments well with no reported adverse effects or local recurrences. DISCUSSION: The use of more dilute preparations of intralesional 5-FU for NMSC may be a means of reducing cumulative dose and dose-dependent adverse reactions while maintaining clinical clearance. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.5058.

Cutaneous crospovidone reaction secondary to subcutaneous injection of buprenorphine.

Crospovidone is an insoluble pharmaceutical disintegrant that has been implicated in a rare foreign body reaction in injection drug users, classically associated with pulmonary angiothrombosis. We recently reported the first known cases of cutaneous crospovidone deposition. We herein report two additional cases with unique clinicopathologic manifestations, both in the setting of suspected injection drug abuse. Additionally, we provide a comprehensive overview of the distinct histomorphology and reproducible histochemistry of crospovidone.

BRAF V600E mutations are not an oncogenic driver of solitary xanthogranuloma and reticulohistiocytoma: Testing may be useful in screening for Erdheim-Chester disease.

BRAF V600E is the predominant oncogenic driver of L-group histiocytoses, which includes Erdheim-Chester disease (ECD); however, limited data exist on the prevalence of this mutation in sporadic XG family lesions. This study sought to determine the incidence of BRAF V600E mutation in a clinically annotated cohort of patients with xanthogranulomas (XG) and reticulohistiocytomas (RH). A retrospective review of 58 lesions was performed, including 41 XG and 17 RH. Immunohistochemistry (HC) and PCR-based methods were performed to evaluate for the BRAF V600E mutation. The BRAF V600E mutation was detected by IHC/PCR in 3 RH from an adult who had no history of arthritis, malignancy, xanthelasma, diabetes insipidus or bone pain. All other XG and RH were negative for the BRAF V600E mutation. No associated systemic diseases were identified in this cohort. Our findings suggest that BRAF V600E mutations are not an oncogenic driver of sporadic XG and solitary RH. Therefore, identification of such a mutation in a patient with multiple lesions should raise consideration for ECD. We also report the first known BRAF V600E mutation in a patient with multiple reticulohistiocytomas.

Cutaneous Crospovidone: A Newly Described Foreign Body Due to Illicit Drug Abuse.

Crospovidone, a polymer of poly N-vinyl-2-pyrrolidone, is an inert insoluble disintegrant found in pharmaceutical tablets. This material has been encountered in the lungs of intravenous drug users and embolized with other components such as talc and microcrystalline cellulose. More recently, crospovidone has also been described in the gastrointestinal tract. We present 2 cases of cutaneous crospovidone deposition resulting from subcutaneous injection of crushed tablets, commonly known as "skin popping." Clinical presentation includes painful, inflamed papules, nodules, or ulcers with overlying eschar. Crospovidone has a distinct and reproducible histochemical staining profile. Histologic recognition of this material is important because it can guide clinicians in their diagnosis and management decisions.

Cutaneous Metastasis of Choriocarcinoma in 2 Male Patients: A Rare Presentation of an Aggressive Malignancy That Dermatopathologists Must Recognize.

Testicular choriocarcinoma needs to be considered in the differential diagnosis of cutaneous metastases in young adult men because of its propensity for early hematogenous dissemination. Furthermore, the diagnosis may not be suspected in many cases in which there is clinically no testicular enlargement. This highly aggressive germ cell tumor typically metastasizes to the liver, lungs, and brain. Skin metastasis is exceedingly rare with only 22 cases previously reported in the world literature. We herein report 2 additional cases: a 25-year-old man and a 32-year-old man, both of whom were treated for mixed germ cell tumors and developed multiple cutaneous metastases to the head.

Validation of a performance-based assessment of cognitive functional ability in Parkinson's disease.

BACKGROUND: Outcome measures that capture functional abilities related to cognition offer the potential to demonstrate real-world effectiveness of cognitive-enhancing treatments. However, distinguishing functional disability related to cognition from that attributed to motor symptoms can be difficult in PD. A performance-based functional assessment allows for direct observation of activity of daily living skills and separation of cognitive from motoric disabilities. OBJECTIVES: Validate the University of California San Diego Performance-Based Skills Assessment in PD. METHODS: One hundred PD participants, ranging from normal cognition to dementia, completed the University of California San Diego Performance-Based Skills Assessment, a performance-based measure of cognitively demanding activities of daily living, as well as a neuropsychological battery and motor examination. Cognitive classification was determined by consensus conference, blinded to University of California San Diego Performance-Based Skills Assessment scores. Psychometric properties of the University of California San Diego Performance-Based Skills Assessment, including internal consistency, test-retest and inter-rater reliability, and discriminant validity for dementia, were examined. RESULTS: The University of California San Diego Performance-Based Skills Assessment demonstrated strong internal consistency (Cronbach's α = 0.82) and test-retest reliability (r = 0.89) and correlated strongly with global cognition (Mattis Dementia Rating Scale: r = 0.80; P < 0.001). University of California San Diego Performance-Based Skills Assessment regression models indicated greater contribution from cognitive explanatory variables (marginal partial: R2 = 0.33) than motor variables (marginal partial: R2 = 0.05), controlling for age, education, disease duration, and l-dopa equivalent dose. Additionally, the University of California San Diego Performance-Based Skills Assessment exhibited strong discriminant validity for dementia (area under the curve = 0.91). CONCLUSIONS: The University of California San Diego Performance-Based Skills Assessment is a valid measure of functional abilities related to cognition rather than motor symptoms in PD. Furthermore, it reliably distinguishes demented from nondemented participants. The University of California San Diego Performance-Based Skills Assessment may be considered as an outcome measure that combines cognitive and functional abilities in treatment trials for cognitive impairment in PD. © 2018 International Parkinson and Movement Disorder Society.

International trial of online auditory training programme for distinguishing innocent and pathological murmurs.

AIM: Recognition of normal and abnormal heart sounds and murmurs is an important but declining clinical skill among practitioners. Current teaching methods are often ineffective. This may result from inadequate repetition and normal-abnormal comparisons needed for auditory recognition. This paper describes a rapid new method of teaching murmur recognition using principles of auditory training. METHODS: Participants were 120 Australian and 42 Canadian medical students. The medical students were randomised to intervention and control (no intervention) groups. The 1-h online programme structured like a computer game used auditory training methodology to teach students to distinguish between innocent and pathological murmurs. Participants underwent pre- and post-testing on 20 paediatric murmurs. Post-testing occurred immediately following training and after 2 months. Twenty-two Canadian medical students were retested 1 year later with a brief mastery-style reinforcement programme. RESULTS: Median pre- and post-test scores improved in about 1 h from 75-95% (P < 0.001) for Australian students and 85-95% (P = 0.004) for Canadian students. Two-month post-test scores declined for Australian students to 85% (P = 0.001), and for Canadian students to 85% (P = 0.02). Australian controls had no significant change during the study period, whereas Canadian controls improved slightly. The group receiving reinforcement after 1 year had a median final score of 90%. CONCLUSIONS: This auditory training programme rapidly teaches students to distinguish innocent and pathological murmurs with at least 90% accuracy. The skill declines within 2 months but can be restored with brief mastery reinforcement 1 year later.

Histological spectrum of cutaneous herpes infections.

Herpes simplex virus and varicella zoster virus are double-stranded DNA viruses that commonly infect humans, resulting in cutaneous manifestations. Diagnosis is generally made based on clinical findings; however, when the presentation is atypical, biopsy can aid in making a correct diagnosis. The classic histopathological findings of herpetic infection are well established (acantholysis, ballooning degeneration, intranuclear inclusions, multinucleation, necrosis, and formation of vesicles or ulcers). Herpes infection can also cause histopathological changes in many dermal structures. Furthermore, herpes can masquerade as a variety of hematologic malignancies or benign cutaneous conditions. The histopathological spectrum of herpes infections is reviewed and discussed.

Molluscum contagiosum of the areola and nipple: case report and literature review.

Molluscum contagiosum is a common cutaneous infection caused by a double-stranded DNA poxvirus. Skin lesions classically present as small, flesh-colored papules with central umbilication. Lesions are frequently seen on the face, trunk, and extremities of children, or on the genitals of young adults as a sexually transmitted infection. Molluscum contagiosum on the nipple or areola has only been previously described in 4 women. We describe a woman with molluscum contagiosum on the left areola and review the clinical characteristics and histological findings of patients who developed molluscum contagiosum of the nipple or areola.

Brain atrophy rates in patients with multiple sclerosis on long term natalizumab resembles healthy controls.

BACKGROUND: Clinically stable multiple sclerosis (MS) patients often have negligible inflammatory MRI changes. Brain atrophy may provide insight into subclinical disease progression. The objective was to compare brain atrophy rates in stable patients on long term natalizumab treatment vs. age and gender matched healthy non-MS controls (HC) prospectively over two-years examining brain volume, cognition, and patient reported outcomes (PROs). METHODS: MS patients treated with natalizumab for a minimum of 2 years, age 18-60 were recruited and compared with age- and gender-matched healthy controls (HC). Both groups were followed prospectively to obtain two years of consecutive magnetic resonance imaging, clinical and PRO data. Baseline normalized brain volume (NBV), yearly T2 lesion volume (T2LV), and percent brain volume change (PBVC) were measured using SIENAX, JIM 6.0, and SIENA respectively. Neuropsychological tests from the MACFIMS battery were selected to optimize assessments for impairments in the domains of information processing speed and memory. Patient reported outcomes (PROs) for domains of physical, mental and social quality of life were evaluated using the NeuroQol short forms. RESULTS: Forty-eight natalizumab and 62 HC completed all study visits. At baseline, unadjusted mean NBV (natalizumab=1508.80cm (Popescu et al., 2013) vs. HC=1539.23cm (Popescu et al., 2013); p=0.033) and median baseline T2LV (natalizumab=1724.62mm (Popescu et al., 2013) vs. HC=44.20mm (Popescu et al., 2013); p=<0.0001) were different. The mean PBVC at year 2, adjusted for gender and baseline age was -0.57% (CI: 0.7620, -0.3716) for natalizumab and -0.50% (-0.7208, -0.2831) for HC, but the difference between groups was not statistically significant (0.073%; p=0.62). Over the 2-year period, HC demonstrated mild improvements in some cognitive tests vs. natalizumab subjects. However, PROs were similar between the two groups. CONCLUSION: Stable MS patients on natalizumab have similar brain volume loss as people who do not have MS, suggesting normalization of brain atrophy.

Volumetry of the human amygdala - an anatomical study.

A striking feature of the studies that have addressed the measurement of the amygdala is the wide range of volumes encountered, with reports of volumes ranging from 1 to almost 4 cm(3). Another striking feature is the number of discrepancies in the landmarks adopted for manual tracing in magnetic resonance imaging (MRI). The goal of our study was to assess the anatomical volume of the amygdala on the basis of its cytoarchitecture while comparing the differences in age and sex. This study was performed on 21 normal male brains (mean age of 56.8 years) and 9 normal female brains (mean age of 61.2 years). The volume of the amygdala was measured by planimetry of Nissl-stained serial sections using ImageJ software. To address the complexity of the amygdala, we elected to use two types of amygdalar measurement that differ mainly in the definition of anterior pole boundaries. The average size of the classic amygdala was 1.24 cm(3) (S.D.=0.14), while the average size of the amygdala with wider borders was 1.63 cm(3) (S.D.=0.2). No interhemispheric or intersexual differences were observed for either type of amygdalar measurement. Neither sex revealed any statistically important relationship between volume of the amygdala and age. Our study was concerned exclusively with the anatomical volume of the amygdala rather than the MRI volume. Nevertheless, our results may have important implications for MRI studies because as of yet there is no gold standard for manual volumetry of the amygdala.

Are Established Embedded Performance Validity Test Cut-Offs Generalizable to Patients With Multiple Sclerosis?

OBJECTIVE: Data for the use of embedded performance validity tests (ePVTs) with multiple sclerosis (MS) patients are limited. The purpose of the current study was to determine whether ePVTs previously validated in other neurological samples perform similarly in an MS sample. METHODS: In this retrospective study, the prevalence of below-criterion responding at different cut-off scores was calculated for each ePVT of interest among patients with MS who passed a stand-alone PVT. RESULTS: Previously established PVT cut-offs generally demonstrated acceptable specificity when applied to our sample. However, the overall cognitive burden of the sample was limited relative to that observed in prior large-scale MS studies. CONCLUSION: The current study provides initial data regarding the performance of select ePVTs among an MS sample. Results indicate most previously validated cut-offs avoid excessive false positive errors in a predominantly relapsing remitting MS sample. Further validation among MS patients with more advanced disease is warranted.

Brain Atrophy Rates for Stable Multiple Sclerosis Patients on Long-Term Fingolimod versus Glatiramer Acetate.

Background: Clinically stable multiple sclerosis (MS) patients on long-term therapy often have negligible acute inflammation on MRI. Brain atrophy may provide insight into subclinical disease progression in such populations. Objective: This study aims to compare brain atrophy for age- and gender-matched MS patients treated for >2 years with fingolimod (FTY) or glatiramer acetate (GA), examining brain volume, cognition, and patient-reported outcomes (PROs). Methods: Stable relapsing-MS patients, age 18-60, on FTY or GA for >2 years were followed up for 2 years. MRI brain and lesion volumes, cognitive measures, and PROs were collected at baseline and annually. Results: Forty-four FTY and forty-three GA patients completed baseline and year 2 visits. No differences in age, gender, or education were observed. Median EDSS was 2.0GA and 2.5FTY (p = 0.22). Treatment duration was longer for GA, 6.50GA vs. 3.73FTY years (p < 0.001). Baseline geometric mean T2LV were different, GA = 1,009.29 cm3 vs. FTY = 2,404.67 cm3 (p = 0.0071). Baseline brain volumes were similar, GA = 1,508 cm3 vs. FTY = 1,489 cm3 (p = 0.2381). Annualized atrophy rates, adjusted for baseline and at mean baseline value, were GA = -0.2775% vs. FTY = -0.2967% (p = 0.7979). No differences in cognitive measures or PROs were observed. Conclusions: Stable MS patients on long-term treatment with FTY and GA have similar brain volume loss rates. Differences in baseline disease severity may suggest patients with more aggressive disease treated with FTY may achieve similar brain volume loss rates as patients with milder baseline disease on GA.

Association of MRI Measurements with Cognitive Outcomes After STN-DBS in Parkinson's Disease.

OBJECTIVES: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for improving the motor symptoms of Parkinson's disease (PD). Overall, cognitive function remains stable after STN-DBS in most patients. However, cognitive decline, specifically in the verbal fluency domain, is seen in a subset of STN-DBS patients. Currently, predictors of cognitive decline in PD patients treated with STN-DBS are not well known. Thus, identification of presurgical predictors might provide an important clinical tool for better risk-to-benefit assessment. This study explores whether whole brain white matter lesion (WML) volume, or hippocampal and forebrain volumes, measured quantitatively on MRI, are associated with cognitive changes following STN-DBS in PD patients. METHODS: We conducted a retrospective study using presurgical, and ≥ 6-month postsurgical neuropsychological (NP) evaluation scores from 43 PD patients with STN-DBS. Mean pre/post NP test scores for measures of executive function, attention, verbal fluency, memory, and visuospatial function were analyzed and correlated with WML volume, and brain volumetric data. RESULTS: Although cognitive measures of verbal fluency, executive function, attention, memory, and visuospatial function showed declines following STN-DBS, we observed limited evidence that white matter lesion burden or cortical atrophy contributed to cognitive change following STN-DBS. CONCLUSIONS: These results suggest that post-STN-DBS cognitive changes may be unrelated to presurgical WML burden and presence of cortical atrophy.

Individual growth curve analysis of APOE epsilon 4-associated cognitive decline in Alzheimer disease.

BACKGROUND: The apolipoprotein E epsilon4 (APOE epsilon4) allele is associated with an increased risk of developing Alzheimer disease (AD). However, findings regarding an association between the APOE epsilon4 allele and the rate of decline in AD have been mixed. OBJECTIVE: To examine the relationship between the APOE epsilon4 allele and the rate of cognitive and functional decline in AD using individual growth curve analyses. DESIGN: Longitudinal cohort study. SETTING: Alzheimer Disease Research Center at Baylor College of Medicine. PATIENTS: A total of 189 patients meeting NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) criteria for probable AD at baseline who underwent annual follow-up evaluations for at least 2 years. MAIN OUTCOME MEASURES: Individual growth curve parameters derived from baseline and follow-up performance on global and specific measures of cognitive and functional abilities. RESULTS: Patients with 2 APOE epsilon4 alleles exhibited a slower rate of decline on measures of global cognitive functioning and functional abilities. No significant association was detected between the APOE epsilon4 allele and the rate of decline on measures of specific cognitive functions. CONCLUSIONS: Although the APOE epsilon4 allele is associated with an increased risk of developing AD, it seems that having 2 APOE epsilon4 alleles is associated with a slower clinical course. These findings are consistent with hypotheses that the biological processes contributing to the onset of AD are different from those involved in determining its clinical course.

Sleep in patients with neurologic and psychiatric disorders.

Given the widely recognized association between many neurologic and psychiatric disorders and significant sleep disturbances, the International Classification of Sleep Disorders Diagnostic and Coding Manual recognizes "Sleep Disorders Associated with Mental, Neurologic, or Other Medical Disorders" as one of four major classification categories. Such sleep disturbances may exacerbate symptoms of the underlying neurologic or psychiatric disorder or produce further adverse medical, behavioral, or psychosocial consequences. Therefore, adequate assessment and recognition of sleep disturbances in these populations is essential. This article includes a summary of neurologic systems influencing sleep that may be affected by neurologic and psychiatric disorders, followed by a brief review of sleep disturbances associated with many common neurologic and psychiatric disorders.

Solitary pilar leiomyoma of the nasal dorsum: case report and literature review.

Cutaneous leiomyoma is an infrequently occurring benign tumor that arises from smooth muscle in the skin. Pilar leiomyoma, a subtype of cutaneous leiomyoma, arises from the arrector pili muscle associated with hair follicles. Pilar leiomyoma, particularly in the head and neck region, is rare and frequently misdiagnosed. We report one patient who developed pilar leiomyoma of the nasal dorsum, explore the differential diagnosis and review the characteristics of previously reported individuals with pilar leiomyoma of the nasal dorsum.

Helping family physicians improve their cardiac auscultation skills with an interactive CD-ROM.

INTRODUCTION: There have been few studies of the cardiac auscultation skills of residents and family physicians. This study assessed a group of family physicians' cardiac auscultation skills and use of a computerized self-instructional program to improve these skills. METHODS: Forty-two volunteer family physicians participated in an initial assessment of cardiac auscultation skills using test recordings of 12 common heart sounds. They were provided with a CD-ROM instructional program and were asked to devote 15 hours of self-study to the program and to return in 9 months for reassessment. RESULTS: The 42 family physicians in the initial assessment identified 39% of the heart sounds. Twenty-one returned for reassessment and showed significant improvement. Their initial mean score was 4.3 of 12 (35%), and their final mean score was 8.0 of 12 (67%). They found the CD-ROM program to be a valuable resource. The feature most liked was the unlimited opportunity to review sounds, cases, and tutorials. Most frequent problems related to computer access or skills. Eleven respondents reported using the program to resolve patient problems in their clinical practices. DISCUSSION: The cardiac auscultation skills of a group of volunteer family physicians showed low initial scores that improved significantly after self-study with a CD-ROM instructional program. The program was a valuable self-instructional aid, and physicians used it as a resource in clinical practice. However, only 50% of the initial group completed the self-study and returned for final assessment. Providing more support and assistance in the initial phase, especially with computer use, may enable completion of similar computerized self-study programs.