Evaluating the sources and types of dietary and nutritional advice for patients with alopecia areata.

Although there are now two Food and Drug Administration (FDA)-approved treatments for severe alopecia areata (AA), many patients still resort to non-medical therapies and lifestyle modifications such as diet and nutrition. The goal of this study was to evaluate the sources and types of dietary and nutritional advice for patients with AA. We distributed a cross-sectional national survey using the National Alopecia Areata Foundation's email list-serv between August 2022 and January 2023. Most respondents were White (76.3%), employed (58.3%) females (84.4%) with a mean age of 52 years. 163 (19.1%) respondents reported receiving diet and/or nutritional advice and 418 (49.5%) respondents reported searching for diet and/or nutritional advice to help with their AA; the most common source of advice was online. The most common dietary changes were the use of vitamins or supplements (30.6%), adherence to diets (23.2%), and the addition of specific foods (21.4%). 209 (50.2%) respondents reported no change in their disease and 197 (47.4%) respondents reported no change in how they felt about their disease compared to before they tried the change. Many AA patients search for or receive unsolicited dietary and nutritional advice and subsequently modify their behavior to manage their disease. However, the efficacy of these changes is unclear. Providers should be mindful of the sources through which patients obtain treatment information as well as the lifestyle changes patients make to counsel patients with evidence-based information. Further investigation is needed to better characterize the direct and indirect costs of dietary and nutritional modification in the treatment of AA.

Perioperative management and clinical outcomes of peristomal pyoderma gangrenosum.

Peristomal pyoderma gangrenosum is an uncommon subtype of pyoderma gangrenosum mainly affecting stoma sites of patients with inflammatory bowel disease. While surgical treatments are often used to assist healing, little is known about the relationship between surgical interventions and the rate of recurrence of peristomal pyoderma gangrenosum. The aim of this study was to identify patient and clinical factors associated with peristomal pyoderma gangrenosum recurrence following surgical intervention. A multi-institutional retrospective case series and literature review was conducted to evaluate patient characteristics and perioperative treatment. Patients of any age with peristomal pyoderma gangrenosum undergoing surgical operations related to their pyoderma gangrenosum or due to another comorbidity were included. Descriptive statistics were used to characterize demographic information. Associations were evaluated using Wilcoxon's rank-sum test for continuous variables and Fisher's exact test for categorical data. Thirty-seven cases were included, 78.3% of which had a history of inflammatory bowel disease. Overall, 13 (35.1%) cases experienced recurrence at 30 days. There was no significant association identified between patient demographics, stoma location, surgical intervention, or perioperative treatment with rate of recurrence at 30 days post-operation. While no clinical risk factors or treatments were associated with recurrence, our work underscores the importance of a multidisciplinary approach to this disease to address gastrointestinal, dermatologic, and surgical components of treatment.

Skin cancer in renal transplant recipients: outcomes from a safety net hospital in Boston.

BACKGROUND: Renal transplant recipients (RTRs) are prone to skin cancer due to the immunosuppression required to maintain graft function. Existing studies of skin cancer in RTRs focus on patients with Fitzpatrick skin types I-II, with limited documentation of incidence in skin types III-VI. This study seeks to better characterize skin cancers in RTRs with skin types III-VI. PRIMARY AIMS: Compare the incidence of skin cancer in RTRs of skin types I-II with skin types III-VI. SECONDARY AIMS: Explore the association between the development of skin cancer and other contributing factors in RTRs of skin types I-VI. METHODS: Retrospective chart review of RTRs at a single institution between January 1, 2000 and December 31, 2022. Patients were followed from the date of transplant to the last clinical follow-up or death. 777 RTRs were included in the study, including 245 patients with Fitzpatrick skin types I-II and 532 with skin types III-VI. A total of 48 patients developed NMSCs, 2 patients developed melanoma, and 3 patients developed Kaposi sarcoma. RESULTS AND CONCLUSIONS: There is a higher incidence of skin cancer in RTRs with Fitzpatrick skin types III-VI compared to the reported incidence among non-transplant recipients of the same skin types, but the incidence remains considerably lower compared to RTR of skin types I-II.

Concomitant treatment of sustained ventricular tachycardia and hypertrophic cardiomyopathy with transcoronary ethanol ablation: a case report.

Background: The recommended treatment for recurrent ventricular tachycardia in patients with hypertrophic cardiomyopathy that is not amenable to defibrillator implantation due to shock burden is radiofrequency ablation. In patients with deeply intramural foci of ventricular tachycardia, traditional unipolar ablation has a lower probability of success. Case summary: A 66-year-old Caucasian man was admitted with ventricular tachycardia, which recurred despite antiarrhythmic drugs. On cardiac magnetic resonance imaging, he was discovered to have septal hypertrophic cardiomyopathy, which was not significant on echocardiogram. The focus of ventricular tachycardia was suspected to be buried deeply within the hypertrophic segment as localized by late gadolinium enhancement. The patient underwent transcoronary ethanol ablation, which abated the ventricular tachycardia while also completely decreasing his invasively measured left ventricular outflow tract obstruction gradient from 45 to 17 mmHg. Discussion: Transcoronary ethanol ablation may be successfully applied to simultaneously treat ventricular arrhythmia superimposed within a segment of hypertrophic cardiomyopathy. Further data are needed to evaluate long-term success of this strategy vs. traditional radiofrequency ablation.

Mortality and Autopsy Findings in Patients with Pyoderma Gangrenosum: A Multi-Institutional Series.

INTRODUCTION: Pyoderma gangrenosum (PG) is a rare ulcerative skin condition with an increased risk of mortality compared to the general population. The causes of this increased risk are not well understood. Misdiagnosis is common in PG, and many studies are limited by the inclusion of misdiagnosed cases. The goal of this study was to review autopsy findings, identify causes of death, and identify factors that may worsen outcomes among deceased patients confirmed to have PG. METHODS: Data was retrospectively reviewed from the electronic medical records at five academic hospitals. A search was conducted for deceased patients with a diagnosis of PG who had an autopsy performed between 2010 and 2020. We report a descriptive analysis of 11 patients and their clinical characteristics, causes of death, and autopsy findings. RESULTS: The average age of death was 62.9 years. Seven patients had at least one underlying condition known to be associated with PG including inflammatory bowel disease, inflammatory arthritis, or a hematologic disorder. The most common cause of death was infection (n = 6, 54.5%), followed by pulmonary embolism (n = 3, 27.3%), and myelodysplastic syndrome (n = 2, 18.2%). Six patients (54.5%) were taking systemic steroids at the time of death. CONCLUSION: The development of PG may shorten life expectancy among those with underlying conditions associated with PG, and common treatments for PG may contribute to the risk of fatal complications. Awareness of the risk of infection, thrombosis, and malignancy among those with PG is necessary for proper management. Further research is needed to explore the relationship between PG and thromboembolism.

Evaluation of Inclusion and Exclusion Criteria for Pyoderma Gangrenosum in Clinical Research: A Systematic Review.

INTRODUCTION: Pyoderma gangrenosum (PG) is a rare, inflammatory dermatologic disease that, as a diagnosis of exclusion with nonspecific histologic features, is difficult to diagnose. As pharmaceutical interest in potential treatments for PG increases, the need for standardized diagnostic criteria to ensure reproducibility, comparability, and external validity of PG research is required. In this study, we aim to characterize the inclusion and exclusion criteria used in the diagnosis of PG in clinical research studies as well as the eligibility of PG in clinical trials. METHODS: A systematic review was conducted to characterize the PG inclusion and exclusion criteria in research studies. An additional search of the USA and international clinical trials databases was conducted as well to capture eligibility criteria for PG trials. RESULTS: Our study revealed a broad range of inclusion and exclusion criteria used to establish the presence or absence of PG. Based on eight distinct categories used to characterize inclusion criteria for research studies, diagnosis by a dermatologist (n = 25, 31.6%), no inclusion criteria listed (n = 21, 26.6%), and clinical and histopathologic features consistent with PG (n = 20, 25.3%) were most common. For current clinical trials, six categories were used to characterize inclusion criteria, of which clinical and histopathologic features consistent with PG (n = 5, 31.3%), identification based on diagnosis of PG (n = 4, 25.0%), and clinical features consistent with PG (n = 3, 18.8%) were the most common. CONCLUSION: This systematic literature review highlights the range of heterogeneity in diagnostic and eligibility criteria used in PG-directed clinical research and current clinical trials and illustrates the need for the development of consensus guidelines and a rigorous framework to enable high-quality future trials for PG.

Eligibility Criteria for Active Ulcerative Pyoderma Gangrenosum in Clinical Trials: A Delphi Consensus on Behalf of the UPGRADE (Understanding Pyoderma Gangrenosum: Review and Assessment of Disease Effects) Group.

At present, there are no standardized guidelines for determining patient eligibility for pyoderma gangrenosum (PG) clinical trials. Thus, we aim to determine which clinical features, histopathological features, or laboratory features should be included in active ulcerative PG clinical trial eligibility criteria for treatment-naïve patients and patients already treated with immunomodulating medications (treatment-exposed patients). This study employed 4 rounds of the Delphi technique. Electronic surveys were administered to 21 international board-certified dermatologists and plastic surgeon PG experts (June 2022-December 2022). Our results demonstrated that for a patient to be eligible for a PG trial, they must meet the following criteria: (i) presence of ulcer(s) with erythematous/violaceous undermining wound borders, (ii) presence of a painful or tender ulcer, (iii) history/presence of rapidly progressing disease, (iv) exclusion of infection and other causes of cutaneous ulceration, (v) biopsy for H&E staining, and (vi) a presence/history of pathergy. These criteria vary in importance for treatment-naïve versus treatment-exposed patients. Given the international cohort, we were unable to facilitate live discussions between rounds. This Delphi consensus study provides a set of specific, standardized eligibility criteria for PG clinical trials, thus addressing one of the main issues hampering progress toward Food and Drug Administration approval of medications for PG.

An Assessment of Current Clinician-Reported and Patient-Reported Outcome Measures for Alopecia Areata: A Scoping Review.

Although progress has been made in developing outcome measures for AA, the use of these measures remains unstandardized. A scoping review was conducted to identify the clinician-reported outcome measures (ClinROMs) and patient-reported outcome measures (PROMs) used in assessing and treating AA, the results of which revealed heterogeneity in AA outcome measures. Of 23 research studies ultimately included, only 2 ClinROMs were used by >15% of studies; likewise, of 110 clinical trials evaluated, numerous outcome instruments were used, but only one ClinROM was used by >5% of trials (Severity of Alopecia Tool). These results suggest the need for consensus and standardization in both research and trial settings.

Skin phototype of participants in laser and light treatments of cosmetic dermatologic conditions: A systematic review.

BACKGROUND: In cosmetic dermatology, lasers and lights treat a variety of hair and skin conditions, including some that disproportionately affect people of color. AIMS: Our systematic review aims to understand the representation of participants with skin phototypes 4-6 in cosmetic dermatologic trials studying laser and light devices. METHODS: A systematic literature search was conducted using search terms "laser," "light," and multiple laser and light subtypes in the PubMed and Web of Science databases. All randomized controlled trials (RCTs) published between January 1, 2010 and October 14, 2021 that studied laser or light devices for cosmetic dermatologic conditions were eligible for inclusion. RESULTS: Our systematic review included 461 RCTs representing 14 763 participants. Of 345 studies that reported skin phototype, 81.7% (n = 282) included participants of skin phototypes 4-6, but only 27.5% (n = 95) included participants of skin phototypes 5 or 6. This trend of excluding darker skin phototypes persisted when results were stratified by condition, laser of study, study location, journal type, and funding source. CONCLUSIONS: Trials studying lasers and lights for the treatment of cosmetic dermatologic conditions need better representation of skin phototypes 5 and 6.

Limb amputation in patients with pyoderma gangrenosum: a multi-institutional case series.

INTRODUCTION: Pyoderma gangrenosum (PG) can represent a diagnostic challenge, leading to missed or delayed diagnosis. With prolonged immunosuppressive therapy, the risk of infections is elevated, predisposing patients to receive anti-infective treatments and, in serious cases, amputations. Limb amputations have been reported as complication of PG misdiagnosis but can also occur as a complication of long-standing PG ulcers. METHODS: We aimed to describe the clinical characteristics of patients with PG leading to limb amputation through a multicenter retrospective case series between 2010 and 2020 including patients with PG who underwent limb amputation. We report a descriptive analysis of these patients' clinical course and outcome. RESULTS: Ten patients with PG who underwent at least one limb amputation were identified. Six were male (60%). Mean age was 65 years. All patients had ulcerative PG on the lower extremities, with a mean PG ulcer duration of 30.6 months. Six patients had PG-related comorbidities such as ulcerative colitis, myelodysplasia, and inflammatory arthritis. Other significant comorbidities included diabetes mellitus (DM) (five patients), coronary artery disease (five patients), and chronic kidney disease (two patients). The majority of patients (8/10) were correctly diagnosed with PG prior to amputation, whereas two patients were misdiagnosed with necrotizing soft tissue infections (NSTIs). All patients received intravenous antibiotics without substantial improvement. Eight patients developed sepsis and shock-like symptoms and the diagnosis of NSTIs was considered. Below-knee amputation was performed in six patients and above-knee amputation in four. Four patients had amputation performed twice because of recurrent NSTIs. Conclusion This multicenter case series sheds light on practice gaps for physician assessing patients with PG, in that limb amputation may result from PG misdiagnosis or complications thereof. Elderly patients (above 65 years) with coexisting lower extremity PG, DM, and/or chronic cardiac or renal disease should be managed with particular care toward preventing infection/NSTIs to prevent further complications such as limb amputations.

Inactivation of the Hippo tumor suppressor pathway promotes melanoma.

Melanoma is commonly driven by activating mutations in the MAP kinase BRAF; however, oncogenic BRAF alone is insufficient to promote melanomagenesis. Instead, its expression induces a transient proliferative burst that ultimately ceases with the development of benign nevi comprised of growth-arrested melanocytes. The tumor suppressive mechanisms that restrain nevus melanocyte proliferation remain poorly understood. Here we utilize cell and murine models to demonstrate that oncogenic BRAF leads to activation of the Hippo tumor suppressor pathway, both in melanocytes in vitro and nevus melanocytes in vivo. Mechanistically, we show that oncogenic BRAF promotes both ERK-dependent alterations in the actin cytoskeleton and whole-genome doubling events, which independently reduce RhoA activity to promote Hippo activation. We also demonstrate that functional impairment of the Hippo pathway enables oncogenic BRAF-expressing melanocytes to bypass nevus formation and rapidly form melanomas. Our data reveal that the Hippo pathway enforces the stable arrest of nevus melanocytes and represents a critical barrier to melanoma development.

Isotretinoin Laboratory Monitoring in Acne Treatment: A Delphi Consensus Study.

Importance: Although isotretinoin may rarely be associated with laboratory abnormalities such as hypertriglyceridemia, the optimal approach to laboratory monitoring is uncertain, and there is wide variation in clinical practice. Objective: To establish a consensus for isotretinoin laboratory monitoring among a diverse, international cohort of clinical and research experts in acne. Design, Setting, and Participants: Using a modified electronic Delphi process, 4 rounds of anonymous electronic surveys were administered from 2021 to 2022. For laboratory tests reaching consensus (≥70% agreement) for inclusion, questions regarding more time-specific monitoring throughout isotretinoin therapy were asked in subsequent rounds. The participants were international board-certified dermatologist acne experts who were selected on a voluntary basis based on involvement in acne-related professional organizations and research. Main Outcomes and Measures: The primary outcome measured was whether participants could reach consensus on key isotretinoin laboratory monitoring parameters. Results: The 22 participants from 5 continents had a mean (SD) time in practice of 23.7 (11.6) years and represented a variety of practice settings. Throughout the 4-round study, participation rates ranged from 90% to 100%. Consensus was achieved for the following: check alanine aminotransferase within a month prior to initiation (89.5%) and at peak dose (89.5%) but not monthly (76.2%) or after treatment completion (73.7%); check triglycerides within a month prior to initiation (89.5%) and at peak dose (78.9%) but not monthly (84.2%) or after treatment completion (73.7%); do not check complete blood cell count or basic metabolic panel parameters at any point during isotretinoin treatment (all >70%); do not check gamma-glutamyl transferase (78.9%), bilirubin (81.0%), albumin (72.7%), total protein (72.7%), low-density lipoprotein (73.7%), high-density lipoprotein (73.7%), or C-reactive protein (77.3%). Conclusions and Relevance: This Delphi study identified a core set of laboratory tests that should be evaluated prior to and during treatment with isotretinoin. These results provide valuable data to guide clinical practice and clinical guideline development to optimize laboratory monitoring in patients treated with isotretinoin.

Prevalence of Misrepresentation of Nonphysician Clinicians at Dermatology Clinics.

INTRODUCTION: To evaluate the use of inaccurate terminology used by dermatology practices to describe the training and qualifications of their nonphysician clinicians (NPCs) when new patients are booking appointments. METHODS: Clinics were randomly selected and called to determine the first available appointment for a new patient with a new and changing mole. If the receptionist confirmed the first-offered appointment was with an NPC, the encounter was included in this study. If receptionists used inaccurate terminology to describe the NPCs and their qualifications, this instance was recorded along with the specific language that they used. RESULTS: A total of 344 unique dermatology clinics were contacted on February 27, 2020, in 25 states. Phone calls at 128 clinics (37.2%) met our inclusion criterion. Inaccurate language was used to describe NPCs at 23 (18%) unique clinic locations across 12 states, with "dermatologist," "doctor," "physician," and "board-certified" being used to describe NPCs as the most common inaccurate terms. CONCLUSION: These findings demonstrate that front office staff at dermatology clinics use inaccurate and potentially misleading terminology to refer to NPCs working in their clinics. While we cannot establish whether this is intentional or due to a lack of training, additional focus should be placed on accurately representing provider qualifications to patients.

Gut instincts: vitamin D/vitamin D receptor and microbiome in neurodevelopment disorders.

The gut microbiome regulates a relationship with the brain known as the gut-microbiota-brain (GMB) axis. This interaction is influenced by immune cells, microbial metabolites and neurotransmitters. Recent findings show gut dysbiosis is prevalent in autism spectrum disorder (ASD) as well as attention deficit hyperactivity disorder (ADHD). There are previously established negative correlations among vitamin D, vitamin D receptor (VDR) levels and severity of ASD as well as ADHD. Both vitamin D and VDR are known to regulate homeostasis in the brain and the intestinal microbiome. This review summarizes the growing relationship between vitamin D/VDR signalling and the GMB axis in ASD and ADHD. We focus on current publications and summarize the progress of GMB in neurodevelopmental disorders, describe effects and mechanisms of vitamin D/VDR in regulating the microbiome and synoptically highlight the potential applications of targeting vitamin D/VDR signalling in neurodevelopment disorders.

Identification and characterization of transcript polymorphisms in soybean lines varying in oil composition and content.

BACKGROUND: Variation in seed oil composition and content among soybean varieties is largely attributed to differences in transcript sequences and/or transcript accumulation of oil production related genes in seeds. Discovery and analysis of sequence and expression variations in these genes will accelerate soybean oil quality improvement. RESULTS: In an effort to identify these variations, we sequenced the transcriptomes of soybean seeds from nine lines varying in oil composition and/or total oil content. Our results showed that 69,338 distinct transcripts from 32,885 annotated genes were expressed in seeds. A total of 8,037 transcript expression polymorphisms and 50,485 transcript sequence polymorphisms (48,792 SNPs and 1,693 small Indels) were identified among the lines. Effects of the transcript polymorphisms on their encoded protein sequences and functions were predicted. The studies also provided independent evidence that the lack of FAD2-1A gene activity and a non-synonymous SNP in the coding sequence of FAB2C caused elevated oleic acid and stearic acid levels in soybean lines M23 and FAM94-41, respectively. CONCLUSIONS: As a proof-of-concept, we developed an integrated RNA-seq and bioinformatics approach to identify and functionally annotate transcript polymorphisms, and demonstrated its high effectiveness for discovery of genetic and transcript variations that result in altered oil quality traits. The collection of transcript polymorphisms coupled with their predicted functional effects will be a valuable asset for further discovery of genes, gene variants, and functional markers to improve soybean oil quality.

Assessment of a novel approach to evaluate the outcome of endoscope reprocessing.

OBJECTIVE: To investigate and evaluate the use of a portable luminometer system for detecting contamination following the reprocessing and high-level disinfection of flexible endoscopes. DESIGN: Random sampling of endoscopes spaced at 1- to 2-week intervals following normal use in patients. METHODS: Portable luminometer system testing of 31 endoscopes undergoing reprocessing, 63 stored endoscopes, and 15 reprocessed endoscopes that underwent in-depth microbiological analysis. For testing with the portable luminometer system, samples were collected by swabbing a 100-cm2 shank surface area and the internal tip end orifice. Standardization of portable luminometer system results was performed in vitro by comparison of serial dilutions of known quantities of microorganisms and blood, tested before and after sterilization by autoclave. Microbiological analysis included Gram stain, culture for aerobic bacteria, and gene probes for Mycobacterium tuberculosis, herpes simplex viruses 1 and 2, and Cytomegalovirus. Trichrome and calcofluor white stains were used to detect parasites and fungi. Legionella was detected by stain with fluorescent-labeled monoclonal antibody. SETTING: The gastroendoscopy unit of a Veterans Affairs hospital. RESULTS: The portable luminometer system was capable of detecting microbial and cellular contamination of flexible endoscopes following high-level disinfection and reprocessing. The sensitivity of the assay was sufficient for detecting low-level contamination. CONCLUSIONS: The system provided a rapid microbiological outcome monitor for the cleaning and disinfection process. The system was easy to use and relatively accurate.

Hospitalization for community-acquired pneumonia: the pneumonia severity index vs clinical judgment.

STUDY OBJECTIVES: (1) To define clinical factors that could justify hospital admission among patients with community-acquired pneumonia (CAP) with risk classes of I or II. (2) To determine the positive predictive value of the pneumonia severity index as the sole indicator for detecting inappropriate hospitalizations among patients with CAP. DESIGN: Retrospective observational study. SETTING: University of Louisville Hospital and the Veterans Affairs Medical Center of Louisville, KY. PATIENTS: Consecutive adult patients fulfilling the criteria for CAP who were admitted to the hospital between October 1997 and May 2000. MEASUREMENTS AND RESULTS: The medical records of hospitalized patients with CAP having a risk class of I or II were identified and further reviewed to determine whether there existed a clinical basis to justify hospitalization. Of a total of 328 patients, 86 had a risk class of I or II. Among these, 72 had clinical factors that justified their hospital admission. These factors, in frequency of occurrence, included the following: medical conditions other than CAP that required hospitalization, 31 patients (43%); social needs, 13 patients (18%); oral intolerance, 10 patients (14%); failure of outpatient therapy, 10 patients (14%); noncompliance, 6 patients (9%); suspicion of sepsis, 1 patient (1%); and hypoxemia, 1 patient (1%). Among the 86 patients with low risk classes (ie, classes I or II), 14 were found to be inappropriately hospitalized, yielding a positive predictive value of 16%. CONCLUSIONS: The pneumonia severity index, used as the sole indicator for detecting inappropriate hospitalizations, has an unacceptably low positive predictive value. This is due primarily to the severity of comorbid conditions requiring in-hospital care in patients with a nonsevere pneumonia. According to our study, the pneumonia severity index should not be used as the sole indicator with which to define inappropriate hospitalization.