Hyaluronidase Injections for Oral Microstomia in Systemic Sclerosis and Mixed Connective Tissue Disease.

This case series evaluates hyaluronidase for oral microstomia in a cohort of patients with autoimmune sclerosing disease.

Towards gender equity in artificial intelligence and machine learning applications in dermatology.

There has been increased excitement around the use of machine learning (ML) and artificial intelligence (AI) in dermatology for the diagnosis of skin cancers and assessment of other dermatologic conditions. As these technologies continue to expand, it is essential to ensure they do not create or widen sex- and gender-based disparities in care. While desirable bias may result from the explicit inclusion of sex or gender in diagnostic criteria of diseases with gender-based differences, undesirable biases can result from usage of datasets with an underrepresentation of certain groups. We believe that sex and gender differences should be taken into consideration in ML/AI algorithms in dermatology because there are important differences in the epidemiology and clinical presentation of dermatologic conditions including skin cancers, sex-specific cancers, and autoimmune conditions. We present recommendations for ensuring sex and gender equity in the development of ML/AI tools in dermatology to increase desirable bias and avoid undesirable bias.

Development of a working core outcome set for cutaneous lupus erythematosus: a practical approach to an urgent unmet need.

OBJECTIVE: The lack of standardised outcomes and outcome measures for cutaneous lupus erythematosus (CLE) represents a substantial barrier to clinical trial design, comparative analysis and approval of novel investigative treatments. We aimed to develop a working core outcome set (COS) for CLE randomised controlled trials and longitudinal observational studies. METHODS: We conducted a multistage literature review of CLE and SLE studies to generate candidate domains and outcome measures. Domains were narrowed to a working core domain set. Outcome measures for core domains were identified and examined. RESULTS: Proposed core domains include skin-specific disease activity and damage, investigator global assessment (IGA) of disease activity, symptoms (encompassing itch, pain and photosensitivity), health-related quality of life (HRQoL) and patient global assessment (PtGA) of disease activity. Recommended physician-reported outcome measures include the Cutaneous Lupus Erythematous Disease Area and Severity Index (CLASI) and Cutaneous Lupus Activity IGA (CLA-IGA). For the domains of symptoms, HRQoL and PtGA of disease activity, we were unable to recommend one clearly superior instrument. CONCLUSION: This work represents a starting point for further refinement pending formal consensus activities and more rigorous evaluations of outcome measure quality. In the interim, the proposed working COS can serve as a much-needed guide for upcoming CLE clinical trials.

Differences in Utilization of Nonvideo Telemedicine Visits for Dermatologic Concerns in Underserved Populations During the COVID-19 Pandemic.

Background: Usage of telemedicine for virtual dermatology care during the COVID-19 pandemic on a national scale is poorly characterized, particularly for nonvideo encounters. Objective: We sought to compare utilization of telephone and asynchronous virtual care for dermatologic concerns 3 months before (December 2019-February 2020) and during the pandemic (March-May 2020) across patient populations. Methods: A retrospective study was performed using a national claims database with >280 million patients within the COVID-19 Research Database to identify monthly telephone and asynchronous virtual visits by diagnosis, age, income, and patient race/ethnicity. Results: Although overall visits for dermatologic concerns decreased by 27.2% during the pandemic, telephone and asynchronous visits increased significantly. Patients most likely to use telephone visits during the pandemic were of older age (relative risk ratio [RRR] = 1.043, p < 0.001), African American race (RRR = 2.03, p < 0.001), and household income <$29,000 (RRR = 1.51, p < 0.001). Limitations: Racial and ethnic data were available for 39.04% of patients and income data for 38.1% of patients. Conclusions: Underserved populations including African Americans, elderly, and low-income patients were more likely to utilize telephone formats during the pandemic. Further studies are needed to determine the reasons for these observed differences and whether there is differential quality between nonvideo and video telemedicine encounters to ensure that all patients are given equal access to the highest quality of virtual care.

Cutaneous lupus erythematosus and cardiovascular disease: current knowledge and insights into pathogenesis.

Multiple autoinflammatory diseases, including psoriasis, psoriatic arthritis, and systemic lupus erythematosus, have been linked to increased risk of cardiovascular disease. Inflammation is known to play a key role in the pathogenesis of atherosclerosis, thus the contribution of systemic immune dysregulation, which characterizes such inflammatory conditions, towards the development of cardiovascular disease has garnered considerable interest. Cutaneous lupus erythematosus (CLE) is a chronic inflammatory skin disease, but risk of cardiovascular disease amongst patients with cutaneous lupus is less well known. Observational studies, including those of large nationwide cohorts, have been conducted to examine cardiovascular disease risk in CLE, with varying findings. As with other inflammatory diseases, immunologic mechanisms may provide plausible causal links between CLE and cardiovascular risk. On a macrolevel, several disease-related characteristics may also contribute to cardiovascular risk amongst CLE patients. This represents an area of research that should be prioritized, as understanding cardiovascular disease risk has important clinical implications for CLE patients.

Study on the effectiveness and safety of Foldable Capsular Vitreous Body implantation.

BACKGROUND: Foldable capsular vitreous body (FCVB) was designed to treat severe retinal detachment. The aim of this study was to evaluate the efficacy and safety of the implantation of foldable capsular vitreous body in 1-year follow-up. METHODS: A retrospective analysis was conducted for 20 patients with severe ocular trauma or silicone oil (SO) dependent eyes underwent vitrectomy and FCVB implantation in a 1-year follow-up. All treated eyes were peformed clinical examinations involved the visual acuity (VA) examination, Goldmann applanation tonometer, noncontact specular microscopy, fundus photography, B-Scan examination and optical coherence tomography (OCT). The groups were compared with t-test and the McNemar - Bowker test. RESULTS: In 1-year follow-up, 20 eyes were evaluated in the study. FCVB well supported the vitreous retina in all treated eyes, and 6 treated eyes achieved retinal reattachment 12 months after FCVB implantation. There were no significant differences in VA before and after FCVB implantation (P = 1.000). In addition, the postoperative IOP markedly elevated from the preoperative IOP of 12.90 ± 7.06 mmHg to 15.15 ± 3.36 mmHg (P = 0.000017). The intraocular pressure (IOP) of 10 eyes maintained at a normal level after surgeries. The other 10 eyes showed slightly lower IOP within the acceptable level. Though two patients developed keratopathy and ocular inflammation respectively, other treated eyes were symmetric with fellow eyes showing satisfactory appearance. Moreover, there was no SO emulsification or leakage happened in the observation. CONCLUSIONS: FCVB implantation was an effective and safe treatment in the eyes with severe retinal detachment.

Gallbladder volvulus in a patient with chronic lymphocytic leukemia treated with laparoscopic cholecystectomy.

Gallbladder volvulus is a rare condition that most commonly occurs in elderly women and often mimics acute cholecystitis in its presentation. This condition is a surgical emergency requiring cholecystectomy as it can lead to gallbladder perforation and bilious peritonitis with high morbidity to the patient. An 85-year-old woman with chronic lymphocytic leukemia presented with acute-onset right upper-quadrant abdominal pain and associated nausea with emesis. After admission to the surgical service and initiation of intravenous antibiotics, the patient was taken to the operating room for surgical management due to the persistence of symptoms. Intraoperative findings included a necrotic appearing gallbladder that was twisted on the cystic duct. Laparoscopic cholecystectomy was performed, which was complicated by bile leak requiring endoscopic retrograde cholangiopancreatography with bile duct stenting followed by operative washout. Gallbladder volvulus can be challenging to diagnose. This condition should be suspected in elderly women with acute-onset abdominal pain and imaging concerning for acute cholecystitis. Emergent cholecystectomy is the treatment of choice for gallbladder volvulus.

Thinking Fast Increases Framing Effects in Risky Decision Making.

Every day, people face snap decisions when time is a limiting factor. In addition, the way a problem is presented can influence people's choices, which creates what are known as framing effects. In this research, we explored how time pressure interacts with framing effects in risky decision making. Specifically, does time pressure strengthen or weaken framing effects? On one hand, research has suggested that framing effects evolve through the deliberation process, growing larger with time. On the other hand, dual-process theory attributes framing effects to an intuitive, emotional system that responds automatically to stimuli. In our experiments, participants made decisions about gambles framed in terms of either gains or losses, and time pressure was manipulated across blocks. Results showed increased framing effects under time pressure in both hypothetical and incentivized choices, which supports the dual-process hypothesis that these effects arise from a fast, intuitive system.

Obesity-related DNA methylation at imprinted genes in human sperm: Results from the TIEGER study.

BACKGROUND: Epigenetic reprogramming in mammalian gametes resets methylation marks that regulate monoallelic expression of imprinted genes. In males, this involves erasure of the maternal methylation marks and establishment of paternal-specific methylation to appropriately guide normal development. The degree to which exogenous factors influence the fidelity of methylation reprogramming is unknown. We previously found an association between paternal obesity and altered DNA methylation in umbilical cord blood, suggesting that the father's endocrine, nutritional, or lifestyle status could potentiate intergenerational heritable epigenetic abnormalities. In these analyses, we examine the relationship between male overweight/obesity and DNA methylation status of imprinted gene regulatory regions in the gametes. METHODS: Linear regression models were used to compare sperm DNA methylation percentages, quantified by bisulfite pyrosequencing, at 12 differentially methylated regions (DMRs) from 23 overweight/obese and 44 normal weight men. Our study population included 69 volunteers from The Influence of the Environment on Gametic Epigenetic Reprogramming (TIEGER) study, based in NC, USA. RESULTS: After adjusting for age and fertility patient status, semen from overweight or obese men had significantly lower methylation percentages at the MEG3 (ß = -1.99; SE = 0.84; p = 0.02), NDN (ß = -1.10; SE = 0.47; p = 0.02), SNRPN (ß = -0.65; SE = 0.27; p = 0.02), and SGCE/PEG10 (ß = -2.5; SE = 1.01; p = 0.01) DMRs. Our data further suggest a slight increase in DNA methylation at the MEG3-IG DMR (ß = +1.22; SE = 0.59; p = 0.04) and H19 DMR (ß = +1.37; SE = 0.62; p = 0.03) in sperm of overweight/obese men. CONCLUSIONS: Our data support that male overweight/obesity status is traceable in the sperm epigenome. Further research is needed to understand the effect of such changes and the point of origin of DNA methylation differences between lean and overweight/obese men. Together with our earlier reports on paternal obesity and epigenetic shifts in the offspring, our studies set the groundwork for future studies investigating male gametic methylation aberrations due to paternal lifestyle factors such as obesity.

Discovery of the Highly Potent PI3K/mTOR Dual Inhibitor PF-04979064 through Structure-Based Drug Design.

PI3K, AKT, and mTOR are key kinases from PI3K signaling pathway being extensively pursued to treat a variety of cancers in oncology. To search for a structurally differentiated back-up candidate to PF-04691502, which is currently in phase I/II clinical trials for treating solid tumors, a lead optimization effort was carried out with a tricyclic imidazo[1,5]naphthyridine series. Integration of structure-based drug design and physical properties-based optimization yielded a potent and selective PI3K/mTOR dual kinase inhibitor PF-04979064. This manuscript discusses the lead optimization for the tricyclic series, which both improved the in vitro potency and addressed a number of ADMET issues including high metabolic clearance mediated by both P450 and aldehyde oxidase (AO), poor permeability, and poor solubility. An empirical scaling tool was developed to predict human clearance from in vitro human liver S9 assay data for tricyclic derivatives that were AO substrates.