Rhabdoid tumor predisposition syndrome: A historical review of treatments and outcomes for associated pediatric malignancies.

Rhabdoid tumor predisposition syndrome (RTPS) is a rare disorder associated with malignant rhabdoid tumor of the kidney (RTK), atypical teratoid rhabdoid tumor (ATRT), and/or other extracranial, extrarenal rhabdoid tumors (EERT), and these pediatric malignancies are difficult to treat. Presently, most of the information regarding clinical manifestations, treatment, and outcomes of rhabdoid tumors comes from large data registries and case series. Our current understanding of treatments for patients with rhabdoid tumors may inform how we approach patients with RTPS. In this manuscript, we review the genetic and clinical features of RTPS and, using known registry data and clinical reports, review associated tumor types ATRT, RTK, and EERT, closing with potential new approaches to treatment. We propose collaborative international efforts to study the use of SMARC (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin)-targeting agents, high-dose consolidative therapy, and age-based irradiation of disease sites in RTPS.

Association of neutrophil-lymphocyte ratio with survival in peripheral early-stage non-small cell lung cancer after stereotactic body radiation therapy.

BACKGROUND: The role of neutrophil-lymphocyte ratio (NLR) as a predictor for survival in single fraction SBRT-treated non-small cell lung cancer (NSCLC) patients remains unclear. We performed an observational cohort study to determine the role of pretreatment NLR in predicting survival of early-stage NSCLC patients after single fraction SBRT. METHODS: A single-institution database of peripheral early-stage NSCLC patients treated with SBRT from February 2007 to May 2022 was queried. Optimal threshold of neutrophil-lymphocyte ratio (NLR) was defined based on maximally selected rank statistics. Cox multivariable analysis (MVA), Kaplan-Meier, and propensity score matching were performed to evaluate outcomes. RESULTS: A total of 286 patients were included for analysis with median follow up of 19.7 months. On Cox multivariate analysis, as a continuous variable, NLR was shown to be an independent predictor of OS (adjusted hazards ratio [aHR] 1.06, 95% CI 1.02-1.10, p = 0.005) and PFS (aHR 1.05, 95% CI 1.01-1.09, p = 0.013). In addition, NLR was associated with DF (aHR 1.11, 95% CI 1.05-1.18, p < 0.001). Maximally selected rank statistics determined 3.28 as the cutoff point of high NLR versus low NLR. These findings were confirmed upon propensity matching. CONCLUSIONS: Pretreatment NLR is an independent predictor for survival outcomes of peripheral early-stage NSCLC patients after single fraction SBRT.

Comparison of Survival Outcomes of Single- and Five-Fraction Schedules of Stereotactic Body Radiation Therapy for Early-Stage Central or Peripheral NSCLC.

BACKGROUND: The treatment of early-stage non-small cell lung cancer (NSCLC) with stereotactic body radiation therapy (SBRT) frequently involves different fractionation schemes for peripheral and central tumors due to concerns with toxicity. We performed an observational cohort study to determine survival outcomes for patients with peripheral and central NSCLC treated with SBRT. METHODS: A single-institutional database of patients with early-stage NSCLC treated with SBRT from September 2008 to December 2018 was evaluated. Outcomes were progression-free survival (PFS), overall survival (OS), local failure (LF), nodal failure (NF), and distant failure (DF). Cox multivariable analysis (MVA), Kaplan-Meier plotting, Fine-Gray competing risk MVA, and propensity score matching were performed. RESULTS: A total of 265 patients were included with a median follow-up of 44.2 months. There were 191 (72%) and 74 (28%) patients with peripheral and central tumors treated with single-fraction SBRT to a dose of 27 Gy and five-fraction SBRT to a dose of 50 Gy, respectively. On Cox MVA, there was no difference in OS (adjusted hazards ratio (aHR) of 1.04, 95% CI of 0.74-1.46) or PFS (aHR of 1.05, 95% CI of 0.76-1.45). On Fine-Gray competing risk MVA, there were no differences in LF, NF, or DF. Propensity matching confirmed these findings. CONCLUSION: The survival outcomes of patients treated with SBRT for early-stage NSCLC were equivalent for central and peripheral tumors.

IgG-cleaving endopeptidase enables in vivo gene therapy in the presence of anti-AAV neutralizing antibodies.

Neutralizing antibodies to adeno-associated virus (AAV) vectors are highly prevalent in humans1,2, and block liver transduction3-5 and vector readministration6; thus, they represent a major limitation to in vivo gene therapy. Strategies aimed at overcoming anti-AAV antibodies are being studied7, which often involve immunosuppression and are not efficient in removing pre-existing antibodies. Imlifidase (IdeS) is an endopeptidase able to degrade circulating IgG that is currently being tested in transplant patients8. Here, we studied if IdeS could eliminate anti-AAV antibodies in the context of gene therapy. We showed efficient cleavage of pooled human IgG (intravenous Ig) in vitro upon endopeptidase treatment. In mice passively immunized with intravenous Ig, IdeS administration decreased anti-AAV antibodies and enabled efficient liver gene transfer. The approach was scaled up to nonhuman primates, a natural host for wild-type AAV. IdeS treatment before AAV vector infusion was safe and resulted in enhanced liver transduction, even in the setting of vector readministration. Finally, IdeS reduced anti-AAV antibody levels from human plasma samples in vitro, including plasma from prospective gene therapy trial participants. These results provide a potential solution to overcome pre-existing antibodies to AAV-based gene therapy.

Screening for depression in rosacea patients.

Rosacea patients often are burdened with embarrassment, social anxiety, and psychiatric comorbidities. The Patient Health Questionnaire 9 (PHQ-9) is a validated and reliable self-administered tool for diagnosis of depression and designation of depression severity. This study aimed to examine the relationship between rosacea severity scores and level of depression using a validated rosacea self-assessment tool and the PHQ-9, respectively. Our results indicated that there is a direct relationship between rosacea severity and level of depression, and the PHQ-9 could prove useful in screening for depression in rosacea patients given the high incidence of psychiatric comorbidities in this patient population.

Rosacea Triggers: Alcohol and Smoking.

A variety of triggers are thought to exacerbate rosacea. A validated self-assessment tool and survey was used to study the relationship between rosacea severity and triggers. Subjects were adult patients with a clinical diagnosis of rosacea. Increased severity of disease was significantly associated with consumption of many alcoholic beverages in 1 day and employment at a job requiring extensive sun exposure. The authors' findings may inform physician counseling practices; patients may be provided with practical measures for managing their rosacea, such as limiting alcohol consumption over short periods of time and increasing sun protection, especially in the summer.

Patient Costs Associated with Rosacea.

The recalcitrance of rosacea to many treatment options may prompt patients to spend exorbitant amounts of money on unsubstantiated treatment regimens in an effort to achieve relief. The authors examine the relationship between disease severity and treatment cost across several demographic and socioeconomic strata. Familiarization of evidence-based clinical recommendations and consensus guidelines may equip physicians to educate patients about the most efficacious and cost-effective treatment options to assist patients in making cost-conscious decisions in the management of their rosacea.

Validity and Reliability of a Rosacea Self-Assessment Tool.

The lack of validated rosacea assessment tools is a hurdle in assessing rosacea severity. This article discusses a valid and reliable rosacea severity self-assessment tool (RSAT) to measure rosacea severity. To determine test-retest validity, participants completed the self-assessment twice. A blinded physician graded the participant's disease severity with the Investigator Global Severity (IGS) score. Pearson correlations were used to assess the relationship between the self-assessment measure and the IGS. Test-retest RSAT measurements were correlated. The RSAT represents a valid and reliable tool. This tool may facilitate determination of rosacea severity in survey research studies.

Measurement of Disease Severity in a Population of Rosacea Patients.

Severity of rosacea in populations is not well characterized. A validated self-assessment tool was used to study the relationship between rosacea severity and demographic factors. Subjects were adult patients with a clinical diagnosis of rosacea. Self-assessment severity scores were significantly higher in participants less than 60 years old (mean 3.43 ± 1.07) compared with those greater than or equal to 60 years old (mean 3.09 ± 1.13; P = .04). Self-assessment severity scores were significantly higher in men (3.6 ± 1.3) than women (3.2 ± 1.0; P = .04). The authors conclude that rosacea is more severe in men and younger patients.

Leptomeningeal failure in patients with breast cancer receiving stereotactic radiosurgery for brain metastases.

PURPOSE: Prior studies suggest a high incidence of leptomeningeal failure (LMF) in breast cancer metastatic to brain. This study examines breast cancer-specific variables affecting development of LMF and survival after Gamma-Knife Radiosurgery (GKS). METHODS: Between 2000-2010, 149 (breast) and 658 other-histology patients were treated with GKS. Hormone/HER2, age, local/distant brain failure, prior craniotomy, and prior whole-brain radiotherapy (WBRT) were assessed. Median follow-up was 54months (range, 0-106). Serial MRI determined local and distant-brain failure and LMF. Statistical analysis with categorical/continuous data comparisons were done with Fisher's-exact, Wilcoxon rank-sum, log-rank tests, and Cox-Proportional Hazard models. RESULTS: Of 149 patients, 21 (14%) developed LMF (median time of 11.9months). None of the following predicted for LMF: Her2-status (HR=0.49, p=0.16), hormone-receptor status (HR=1.15, p=0.79), prior craniotomy (HR=1.58, p=0.42), prior WBRT (HR=1.36, p=0.55). Non-significant factors between patients that did (n=21) and did not (n=106) develop LMF included neurologic death (p=0.34) and median survival (8.6 vs 14.2months, respectively). Breast patients who had distant-failure after GKS (65/149; 43.6%) were more likely to later develop LMF (HR 4.2, p=0.005); including 15/65 (23%) patients who had distant-failure and developed LMF. Median time-to-death for patients experiencing LMF was 6.1months (IQR 3.4-7.8) from onset of LMF. Median survival from LMF to death was much longer in breast (6.1months) than in other (1.7months) histologies CONCLUSION: Breast cancer patients had a longer survival after diagnosis of LMF versus other histologies. Neither ER/PR/HER2 status, nor prior surgery or prior WBRT predicted for development of LMF in breast patients.

A Retrospective Review of Treatment Results for Patients With Central Centrifugal Cicatrical Alopecia.

INTRODUCTION: Central centrifugal cicatricial alopecia (CCCA) is a form of scarring alopecia primarily affecting women of African descent on the crown of the scalp. Limited data exists regarding evidence-based treatment for CCCA.

OBJECTIVE: To examine photos of subjects with CCCA before and after treatment in order to evaluate results of treatment and compare results of different treatment regimens.

METHODS: Photographs of 15 subjects with CCCA before and after treatment were evaluated by two blinded investigators who assigned disease severity scores to photographs based on a published scale: Central Scalp Alopecia Photographic Scale in African American Women.

RESUTLS: Median change in severity score (post-treatment severity score - pre-treatment severity score) was 0.5 (P = 0.58) for all 15 subjects receiving a series of 7 to 8 intralesional steroid injections along with topical steroids (Class I/II) +/- minoxidil and +/- anti-dandruff shampoo, indicating worsening of disease after treatment. Subjects receiving minoxidil versus those who did not (0.25 vs 0.5; P = 0.38) and subjects receiving anti-dandruff shampoo versus those who did not (0.0 vs 0.5; P = 0.42) demonstrated no statistically significant difference in pre- and post-treatment severity scores. Of 15 subjects, 5/15 (33.3%) had decreased severity scores, 8/15 (53.3%) had increased severity scores, and 2/15 (13.3%) had no change in severity scores.

CONCLUSIONS: Although no statistically significant difference was found in pre- versus post-treatment disease severity, this may indicate intralesional steroid injections and topical steroids +/- minoxidil and +/- anti-dandruff shampoo halt disease progression.

J Drugs Dermatol. 2017;16(4):317-320.

Rosacea patients seeking advice: Qualitative analysis of patients' posts on a rosacea support forum.

BACKGROUND: Social media have become outlets for patients to voice opinions and ask questions. Since suffering from rosacea is an isolating experience and the disease is poorly understood, patients use social media to expand their knowledge about the condition. OBJECTIVE: To understand rosacea patients' online health information seeking habits to obtain a better insight of their educational needs. METHODS: Ten percent of posts in online rosacea forum composed of 3350 members and 27 051 posts, discussing patient viewpoints and concern, selected by stratified random sampling. Three hundred and nine queries were directly categorized to patients "seeking advice" by two investigators and qualitatively analyzed. RESULTS: Patients primarily sought advice about treatments (n = 155, 50.1%), triggers (n = 53, 17.1%), diet (n = 48, 15.5%), skin care (n = 37, 11.9%) and special presentations of the disease (n = 22, 7.1%). Questions frequently pertained to adverse effects, efficacy and target of therapy (78, 49, 30 posts, respectively). CONCLUSION: Proactively providing reliable resources and comprehensive explanations on treatments, triggers, diet and skin care could be helpful in reducing patients' confusion about rosacea and enhancing rosacea patient-physician relationships.

Cutaneous cryosurgery in the United States.

BACKGROUND: Cryosurgery is a common treatment modality for many dermatological conditions; however, the extent to which it is used and by which medical specialties is not well characterized. OBJECTIVE: To determine the rates of cryosurgery use over time, the top dermatoses treated by cryosurgery, patient demographics and the rate at which practitioners used cryosurgery. METHODS: We used the National Ambulatory Medical Care Survey (NAMCS) from 1993 to 2010 in order to quantify the use of cryosurgery in outpatient offices. For visits where cryosurgery was utilized, the leading diagnoses, treating physician specialties, and patient ages were tabulated. RESULTS: Cryosurgery was most commonly used for treating actinic keratoses (48% of visits), seborrheic keratoses (25% of visits) and verrucae (21% of visits). Dermatologists performed 82% of all cryosurgeries, followed by family/internal medicine physicians (13.6%) and pediatricians (2.8%). The use of cryosurgery for these dermatoses has increased over time (p < 0.0001), especially in patients over the age of 65 years. Physicians in offices with health maintenance organization-based practices were more likely to utilize cryosurgery. LIMITATIONS: Since NAMCS data are cross-sectional, we are unable to determine whether patients tried and failed other treatments. CONCLUSIONS: As the baby boomer generation ages, the demand for cryosurgery will likely further increase.

Training for prescribing in-office and home phototherapy.

BACKGROUND/PURPOSE: One reason phototherapy use is lacking in the United States may be inadequate phototherapy education during dermatology training. The purpose of this study was to estimate the level of dermatology resident training with prescribing phototherapy and to see whether inadequate education may be contributing to the underuse of phototherapy in the United States. METHODS: A questionnaire was developed to assess resident education and comfort with prescribing phototherapy from the resident perspective. Botulinum toxin and radiation therapy training were used as positive and negative controls, respectively. Responses were tabulated and comparisons made using Fisher's exact test and Cochran-Armitage trend test. RESULTS: A total of 88 residents responded. 42% and 81% of respondents reported not receiving didactic education on prescribing in-office and home phototherapy, respectively, compared to 13% for botulinum toxin and 91% for radiation therapy. 29% and 76% reported not being comfortable prescribing in-office and home phototherapy, respectively, compared to 36% for botulinum toxin and 91% for radiation therapy. Phototherapy education satisfaction was positively correlated with comfort of prescribing, and comfort prescribing was positively correlated with actual prescribing of phototherapy. CONCLUSIONS: Training for prescribing phototherapy is lacking. Augmenting phototherapy training may help make home phototherapy more accessible for patients.

Five-Year Trend in the Number of Dermatologic Clinical Drug Trials Registered on ClinicalTrials.gov.

BACKGROUND: There is a reported global decrease in the number of clinical trials conducted in recent years. We aimed to determine if this declining trend can be extrapolated to dermatologic clinical trials. METHODS: We conducted a query of ClinicalTrials.gov for dermatologic clinical trials from 2009 to 2013 for 6 common skin conditions: acne, psoriasis, rosacea, eczema and atopic dermatitis, actinic keratosis, and skin cancer. Results were sorted by condition and number of study subjects. This study did not involve any participants apart from the researchers. RESULTS: Although there is an increasing trend in the number of trials performed annually, the results were not significant (P =.08). The average number of patients per study has not significantly changed (P =.12), but there was a significant increase in the number of large studies (201+ subjects) conducted over time (P =.002). Although there was significant variation based on dermatologic condition studied (global statistic P=.01), only skin cancer demonstrated a significant change in the number of studies registered annually (ß=10.6 studies/year, P =.04). CONCLUSIONS AND RELEVANCE: The sky does not appear to be falling, at least not yet, with regard to continued development of treatments for patients with skin disease.

Trends in Ambulatory Health Care Usage for Adult Acne.

BACKGROUND: The prevalence of acne is increasing among young children but not well characterized in older patients. OBJECTIVE: To determine whether ambulatory health care for adult acne is increasing and whether the average age of adult acne patients seeking care has been increasing over time. METHODS: We performed a retrospective analysis of data from the 1993-2010 National Ambulatory Medical Care Survey for acne visits in ages 25 and older. RESULTS: Average age of adult acne patients increased by 0.13 years per year over the study period. Visits per 100,000 population declined in the 25 to 34 age group (P=.05) and did not change significantly in the 35 to 44 and 45 and older age groups. CONCLUSIONS: The hypothesis that adult acne visits are increasing was not supported, but the average age of adult acne patients seeking care has been rising.

Prevalence of rosacea in community settings.

BACKGROUND: The prevalence of rosacea is poorly characterized. Because selection bias may affect prevalence estimates, there is a need to characterize the prevalence of rosacea outside the clinic setting. OBJECTIVE: To assess the prevalence of rosacea in community settings. METHODS: A clinical research fellow and a medical student stood in public places (a mall, the Department of Motor Vehicles, a grocery store) and examined consecutive individuals who passed by ≤ 2 yards away. They tallied demographic and descriptive data on the subject and included the subject in one of three categories: clearly rosacea, possible rosacea, and definitely no rosacea. Subanalyses by perceived gender, age, race, and rosacea subtype were also performed. Comparisons between groups were made using the Fisher exact test. RESULTS: Considering the prevalence of rosacea among all observed individuals in the community setting, 5.4% (95% CI 3.6-7.8) of individuals had "possible" rosacea and 6% (95% CI 4.1-8.5) of individuals had "definite" rosacea. Older, white individuals with fairer skin types (Fitzpatrick skin types I, II, and III) were more likely to have rosacea. There was no gender predisposition. LIMITATIONS: Distance from subjects made it difficult to assess patients with mild rosacea or a few telangiectasias, as well as ocular rosacea. The study could not assess those individuals who were too embarrassed by their rosacea to be in the public settings observed. Additionally, some subjects may have applied significant makeup in an effort to conceal their rosacea, making assessment difficult. CONCLUSIONS: Based on direct observation of individuals in community settings, rosacea is more common than previously reported in the United States.

The rosacea patient journey: a novel approach to conceptualizing patient experiences.

The motivation for rosacea patients to seek and adhere to treatment is not well characterized. A patient journey is a map of the steps a patient takes as he/she progresses through different segments of the disease from diagnosis to management, including all the influences that can push him/her toward or away from certain decisions. We sought to examine each step of the rosacea patient journey to better understand key patient care boundaries faced by rosacea patients. A PubMed search of articles indexed for MEDLINE as well as a search of the National Rosacea Society Web site (http://www.rosacea.org) were conducted to identify articles and materials that quantitatively or qualitatively described rosacea patient experiences. Current literature pertaining to the rosacea patient journey was summarized. The rosacea patient journey is discussed. It is a useful tool to gain insight on patient experiences. Better understanding of the patient perspective by dermatologists can lead to better patient adherence to treatment and thus improved quality of life and satisfaction.

A significant proportion of thalassemia major patients have adrenal insufficiency detectable on provocative testing.

Advances in chelation therapy and noninvasive monitoring of iron overload have resulted in substantial improvements in the survival of transfusion-dependent patients with thalassemia major. Myocardial decompensation and sepsis remain the major causes of death. Although endocrine abnormalities are a well-recognized problem in these iron-overloaded patients, adrenal insufficiency and its consequences are underappreciated by the hematology community. The aims of this study were to determine the prevalence of adrenal insufficiency in thalassemia major subjects, to identify risk factors for adrenal insufficiency, and to localize the origin of the adrenal insufficiency within the hypothalamic-pituitary-adrenal axis. Eighteen subjects with thalassemia major (18.9±9.3 y old, 7 female) were tested for adrenal insufficiency using a glucagon stimulation test. Those found to have adrenal insufficiency (stimulated cortisol <18 µg/dL) subsequently underwent an ovine corticotropin-releasing hormone (oCRH) stimulation test to define the physiological basis for the adrenal insufficiency. The prevalence of adrenal insufficiency was 61%, with an increased prevalence in males over females (92% vs. 29%, P=0.049). Ten of 11 subjects who failed the glucagon stimulation test subsequently demonstrated normal ACTH and cortisol responses to oCRH, indicating a possible hypothalamic origin to their adrenal insufficiency.