Innovation in Development of Dermatologic Drugs Approved by the US Food and Drug Administration Between 2012 and 2022.

This cross-sectional study characterizes the frequency and degree of innovation of new dermatologic drugs approved by the US Food and Drug Administration (FDA) from 2012 to 2022.

Deep learning on electronic medical records identifies distinct subphenotypes of diabetic kidney disease driven by genetic variations in the Rho pathway.

Kidney disease affects 50% of all diabetic patients; however, prediction of disease progression has been challenging due to inherent disease heterogeneity. We use deep learning to identify novel genetic signatures prognostically associated with outcomes. Using autoencoders and unsupervised clustering of electronic health record data on 1,372 diabetic kidney disease patients, we establish two clusters with differential prevalence of end-stage kidney disease. Exome-wide associations identify a novel variant in ARHGEF18, a Rho guanine exchange factor specifically expressed in glomeruli. Overexpression of ARHGEF18 in human podocytes leads to impairments in focal adhesion architecture, cytoskeletal dynamics, cellular motility, and RhoA/Rac1 activation. Mutant GEF18 is resistant to ubiquitin mediated degradation leading to pathologically increased protein levels. Our findings uncover the first known disease-causing genetic variant that affects protein stability of a cytoskeletal regulator through impaired degradation, a potentially novel class of expression quantitative trait loci that can be therapeutically targeted.

The Role of Telemedicine in Glaucoma Care Triggered by the SARS-CoV-2 Pandemic: A Qualitative Study.

Purpose: To explore and report on how glaucoma care was impacted by the SARS-CoV-2 pandemic (COVID-19) in New York City (NYC) with a specific emphasis on the role of telemedicine. Patients and Methods: This was a qualitative, cross-sectional study that engaged glaucoma clinicians in semi-structured interviews to elicit perspectives on telemedicine and patient care experiences during the pandemic. Interview responses were coded and analyzed thematically. Results: Twenty clinicians participated. Mean participant age was 48.8 ± 12.3 years, and the mean number of years in practice post-glaucoma fellowship was 17.5 ± 12.4 years. Four main themes pertinent to the role of telemedicine triggered by the COVID-19 pandemic were identified: (1) The Need to Ensure Patient and Staff Safety Drove Telemedicine Uptake; (2) Telemedicine Allowed Providers to Address Subjective Complaints; (3) Telemedicine was Discontinued Due To Concerns of Compromised Patient Safety and Measurement Inaccuracy; (4) Technological Advances are Needed for Continued Telemedicine Usage and Uptake in Glaucoma Care. The interviews suggested that telemedicine usage dropped markedly within just a few months during the pandemic, and for most physicians interviewed, telemedicine is no longer part of their clinical practice. Several clinicians reported optimism towards future implementation of telemedicine as the technology develops. Conclusion: This study identified 4 themes outlining the uptake, application, discontinuation and overall perspectives on telemedicine by glaucoma clinicians. The role of telemedicine, as triggered by the COVID-19 pandemic, may have lasting implications for patient safety, continuity of care, and glaucoma care delivery beyond this public health crisis.

Bortezomib-Induced Reticular Eruption in Patient with Multiple Myeloma.

Bortezomib is the first proteasome inhibitor to treat a variety of malignancies and is currently part of the standard of care regimen for the initial treatment of patients with newly diagnosed multiple myeloma. While bortezomib is generally well tolerated, it has been associated with various side effects, which have limited its use in some patients. Here, we describe a unique case with histological confirmation of a reticular eruption that appeared at the site of a subcutaneous administration of bortezomib in a 62-year-old male who was newly diagnosed with IgG kappa multiple myeloma. A skin biopsy was performed, which revealed superficial perivascular dermatitis predominantly composed of lymphocytes with rare eosinophils. The patient was successfully treated with betamethasone dipropionate 0.05% cream. When consulted, dermatologists should advise the oncology team of multiple myeloma patients treated with bortezomib to maintain a high threshold before discontinuing the drug when a patient experiences an atypical, reticular rash following subcutaneous administration. Additionally, potent topical corticosteroids, such as betamethasone dipropionate 0.05% cream, should be considered in managing the cutaneous reticular eruptions related to bortezomib administration, in order to maintain an optimal treatment regimen for patients with multiple myeloma.

Proteomic characterization of acute kidney injury in patients hospitalized with SARS-CoV2 infection.

BACKGROUND: Acute kidney injury (AKI) is a known complication of COVID-19 and is associated with an increased risk of in-hospital mortality. Unbiased proteomics using biological specimens can lead to improved risk stratification and discover pathophysiological mechanisms. METHODS: Using measurements of ~4000 plasma proteins in two cohorts of patients hospitalized with COVID-19, we discovered and validated markers of COVID-associated AKI (stage 2 or 3) and long-term kidney dysfunction. In the discovery cohort (N = 437), we identified 413 higher plasma abundances of protein targets and 30 lower plasma abundances of protein targets associated with COVID-AKI (adjusted p < 0.05). Of these, 62 proteins were validated in an external cohort (p < 0.05, N = 261). RESULTS: We demonstrate that COVID-AKI is associated with increased markers of tubular injury (NGAL) and myocardial injury. Using estimated glomerular filtration (eGFR) measurements taken after discharge, we also find that 25 of the 62 AKI-associated proteins are significantly associated with decreased post-discharge eGFR (adjusted p < 0.05). Proteins most strongly associated with decreased post-discharge eGFR included desmocollin-2, trefoil factor 3, transmembrane emp24 domain-containing protein 10, and cystatin-C indicating tubular dysfunction and injury. CONCLUSIONS: Using clinical and proteomic data, our results suggest that while both acute and long-term COVID-associated kidney dysfunction are associated with markers of tubular dysfunction, AKI is driven by a largely multifactorial process involving hemodynamic instability and myocardial damage.

Acute kidney injury (AKI) is a sudden, sometimes fatal, episode of kidney failure or damage. It is a known complication of COVID-19, albeit through unclear mechanisms. COVID-19 is also associated with kidney dysfunction in the long term, or chronic kidney disease (CKD). There is a need to better understand which patients with COVID-19 are at risk of AKI or CKD. We measure levels of several thousand proteins in the blood of hospitalized COVID-19 patients. We discover and validate sets of proteins associated with severe AKI and CKD in these patients. The markers identified suggest that kidney injury in COVID-19 patients involves damage to kidney cells that reabsorb fluid from urine and reduced blood flow to the heart, causing damage to heart muscles. Our findings might help clinicians to predict kidney injury in patients with COVID-19, and to understand its mechanisms.

Clinician Perspectives for Mental Health Delivery Following COVID-19 in Carceral Settings: A Pilot Study.

We aimed to understand clinician perspectives on mental healthcare delivery during COVID-19 and the utility of tele-mental health services in carceral settings. A survey was administered in November 2022 through the American College of Correctional Physicians listserv. A nationwide sample of 55 respondents included 78.2% male (n = 43) and 21.8% female (n = 12), 49.1% active clinicians (n = 27) and 50.9% medical directors (n = 28), with a median of 12 and mean of 14.5 years working in carceral settings. Most agreed that mental telehealth services could serve as a stopgap amid infection prevention measures and resource-limited settings with an increasing role moving forward (80.0%, n = 44) but may not be sufficient to replace in-person services completely. Access to mental healthcare is vital in helping achieve optimal health during incarceration. Most clinicians in a nationwide survey report an essential role of mental telehealth in the future, although they vary in beliefs on the present implementation. Future efforts should further identify facilitators and barriers and bolster delivery models, particularly via e-health.

Access to Hepatitis C Treatment during and after Incarceration in New Jersey, United States: A Qualitative Study.

Despite effective antiviral therapy for hepatitis C virus (HCV), people who are incarcerated and those returning to the community face challenges in obtaining HCV treatment. We aimed to explore facilitators and barriers to HCV treatment during and after incarceration. From July-November 2020 and June-July 2021, we conducted 27 semi-structured interviews with residents who were formerly incarcerated in jail or prison. The interviews were audio-recorded and professionally transcribed. We used descriptive statistics to characterize the study sample and analyzed qualitative data thematically using an iterative process. Participants included five women and 22 men who self-identified as White (n = 14), Latinx (n = 8), and Black (n = 5). During incarceration, a key facilitator was having sufficient time to complete HCV treatment, and the corresponding barrier was delaying treatment initiation. After incarceration, a key facilitator was connecting with reentry programs (e.g., halfway house or rehabilitation program) that coordinated the treatment logistics and provided support with culturally sensitive staff. Barriers included a lack of insurance coverage and higher-ranking priorities (e.g., managing more immediate reentry challenges such as other comorbidities, employment, housing, and legal issues), low perceived risk of harm related to HCV, and active substance use. Incarceration and reentry pose distinct facilitators and challenges to accessing HCV treatment. These findings signal the need for interventions to improve engagement in HCV care both during and after incarceration to assist in closing the gap of untreated people living with HCV.

Proteomic Characterization of Acute Kidney Injury in Patients Hospitalized with SARS-CoV2 Infection.

Background Acute kidney injury (AKI) is a known complication of COVID-19 and is associated with an increased risk of in-hospital mortality. Unbiased proteomics using biological specimens can lead to improved risk stratification and discover pathophysiological mechanisms. Methods Using measurements of ~4000 plasma proteins in two cohorts of patients hospitalized with COVID-19, we discovered and validated markers of COVID-associated AKI (stage 2 or 3) and long-term kidney dysfunction. In the discovery cohort (N= 437), we identified 413 higher plasma abundances of protein targets and 40 lower plasma abundances of protein targets associated with COVID-AKI (adjusted p <0.05). Of these, 62 proteins were validated in an external cohort (p <0.05, N =261). Results We demonstrate that COVID-AKI is associated with increased markers of tubular injury ( NGAL ) and myocardial injury. Using estimated glomerular filtration (eGFR) measurements taken after discharge, we also find that 25 of the 62 AKI-associated proteins are significantly associated with decreased post-discharge eGFR (adjusted p <0.05). Proteins most strongly associated with decreased post-discharge eGFR included desmocollin-2 , trefoil factor 3 , transmembrane emp24 domain-containing protein 10 , and cystatin-C indicating tubular dysfunction and injury. Conclusions Using clinical and proteomic data, our results suggest that while both acute and long-term COVID-associated kidney dysfunction are associated with markers of tubular dysfunction, AKI is driven by a largely multifactorial process involving hemodynamic instability and myocardial damage.

Online Health Information for Acne Keloidalis Nuchae has a Difficult Level of Readability.

BACKGROUND: Acne keloidalis nuchae (AKN) is an inflammatory disorder primarily seen in individuals of color, characterized by acneiform and keloidal lesions on the occipital scalp/nuchal region. More than 50% of patients with keloids are known to search their condition on the internet. We sought to determine the level of readability of patient education materials (PEM) available to patients. The term 'acne keloidalis nuchae' was searched and screened for the top 100 search results on the Google® search engine. For evaluation, 6 readability metrics (Flesch-Kincaid grade level, Gunning Fog index, Coleman-Liau index, SMOG index, automated readability, and Linsear Write Formula) were collected by entering text from each reference site into an automatic readability calculator for computation. Median readability scores of AKN PEMs ranged from 10.3th to 13.5th grade levels. Overall, readability median above the 8th-grade level were consistently seen across all 6 readability measures, with some median scores reaching university undergraduate levels. More readable educational tools are needed for acne keloidalis nuchae online. J Drugs Dermatol. 2023;21(2):195-196. doi:10.36849/JDD.7110.

Cannabis Use and CKD: Epidemiological Associations and Mendelian Randomization.

Rationale & Objective: The association between cannabis use and chronic kidney disease (CKD) is controversial. We aimed to assess association of CKD with cannabis use in a large cohort study and then assess causality using Mendelian randomization with a genome-wide association study (GWAS). Study Design: Retrospective cohort study and genome-wide association study. Setting & Participants: The retrospective study was conducted on the All of Us cohort (N=223,354). Genetic instruments for cannabis use disorder were identified from 3 GWAS: the Psychiatric Genomics Consortium Substance Use Disorders, iPSYCH, and deCODE (N=384,032). Association between genetic instruments and CKD was investigated in the CKDGen GWAS (N > 1.2 million). Exposure: Cannabis consumption. Outcomes: CKD outcomes included: cystatin-C and creatinine-based kidney function, proteinuria, and blood urea nitrogen. Analytical Approach: We conducted association analyses to test for frequency of cannabis use and CKD. To evaluate causality, we performed a 2-sample Mendelian randomization. Results: In the retrospective study, compared to former users, less than monthly (OR, 1.01; 95% CI, 0.87-1.18; P = 0.87) and monthly cannabis users (OR, 1.15; 95% CI, 0.86-1.52; P = 0.33) did not have higher CKD odds. Conversely, weekly (OR, 1.28; 95% CI, 1.01-1.60; P = 0.04) and daily use (OR, 1.25; 95% CI, 1.04-1.50; P = 0.02) was significantly associated with CKD, adjusted for multiple confounders. In Mendelian randomization, genetic liability to cannabis use disorder was not associated with increased odds for CKD (OR, 1.00; 95% CI, 0.99-1.01; P = 0.96). These results were robust across different Mendelian randomization techniques and multiple kidney traits. Limitations: Likely underreporting of cannabis use. In Mendelian randomization, genetic instruments were identified in the GWAS that included individuals primarily of European ancestry. Conclusions: Despite the epidemiological association between cannabis use and CKD, there was no evidence of a causal effect, indicating confounding in observational studies.

Accelerated Healing from Severe Radiation Dermatitis Using Noncontact, Low-frequency Ultrasound-assisted Saline Wash Therapy.

ABSTRACT: Radiotherapy (RT) is a modality for cancer management that frequently causes critical injury to tissues adjacent to the targeted cancer site. Acute radiation dermatitis (RD) is one of the most common adverse effects of RT and may lead to secondary infection, disfigurement, and discontinuation of therapy. The authors report the efficacy of a multidisciplinary collaboration between radiation oncology, dermatology, and wound care teams in the management of severe, acute RD. This case report describes the use of noncontact, low-frequency ultrasound (NCLFU)-assisted saline wash therapy leading to accelerated healing of severe RD in an older man treated with RT for scalp squamous cell carcinoma. Although NCLFU-assisted saline wash therapy provides gentle debridement of wound surfaces and has demonstrated efficacy in the management of chronic wounds, the potential role for NCLFU therapy in RD management has not yet been explored.

Disparities in the Use of Teledermatology During the COVID-19 Pandemic Lockdown in a Pediatric Dermatology Practice.

Background: The COVID-19 pandemic required a rapid expansion of teledermatology services. Objective: Analyze demographic shifts in a pediatric dermatology practice session with children of color. Methods: A retrospective chart review of pediatric dermatology patients seen in the 4 practice weeks preceding the New York COVID-19 lockdown and comparable teledermatology visits during the COVID-19 pandemic lockdown. Demographic differences (e.g., race, age, gender, and household income) were analyzed. Results: A greater proportion of patients seen were White during lockdown (59.7%), compared with pre-lockdown (43.6%), with a reduction in Asian patients seen in lockdown (6.0%) compared with pre-lockdown (24.5%). A lower proportion of no-show patients (4.3%, 3/70 scheduled) were noted in lockdown compared with pre-lockdown (16%, 18/112). Preferred provider organizations (PPO) and higher-income zip codes were more common for children seen during lockdown. Limitations: The sample addresses a limited New York pediatric dermatology practice during a short time period. Conclusions: White patients and patients with PPO were more likely to access telehealth, supporting disparity in teledermatology services. These results demonstrate reduced health care access for lower-income and Asian children during the COVID-19 pandemic lockdown.