A Rare Case of Renal Angiomyolipoma and Polycystic Kidney Disease in a Patient with Tuberous Sclerosis.

Renal angiomyolipoma (AML) is a rare benign tumor that follows an autosomal dominant inheritance pattern. Its association with polycystic kidney disease is uncommon, with only a handful of cases documented in the literature. The growth of lesions to a significant size may lead to life-threatening complications. We report a case of a 32-year-old female who presented with a palpable mass and bilateral flank pain. Following clinical assessment and CT examination, the patient underwent a left radical nephrectomy. The resected mass measured 9.3 x 8.2 x 7.5 cm, and the subsequent histopathological examination confirmed the diagnosis as renal AML.

Scalp microbiome: a guide to better understanding scalp diseases and treatments.

The scalp microbiome represents an array of microorganisms important in maintaining scalp homeostasis and mediating inflammation. Scalp microbial dysregulation has been implicated in dermatologic conditions including alopecia areata (AA), dandruff/seborrheic dermatitis (D/SD), scalp psoriasis (SP) and folliculitis decalvans (FD). Understanding the impact of scalp microbial dysbiosis gives insight on disease pathophysiology and guides therapeutic decision making. Herein we review the scalp microbiome and its functional role in scalp conditions by analysis of metagenomic medical literature in alopecia, D/SD, SP, and other dermatologic disease.Increased abundance of Malassezia, Staphylococcus, and Brevibacterium was associated with SD compared to healthy controls. A higher proportion of Corynebacterium, actinobacteria, and firmicutes are present in AA patients, and lower proportions of Staphylococcus caprae are associated with worse clinical outcomes. Decreased prevalence of actinobacteria and Propionibacterium and increased firmicutes, staphylococcus, and streptococcus are associated with scalp psoriasis. Studies of central centrifugal cicatricial alopecia (CCCA) suggest scalp microbial composition contributes to CCCA's pro-inflammatory status. The most common organisms associated with FD include methicillin-resistant S. aureus and S. lugdunensis. Antifungals have been a mainstay treatment for these diseases, while other alternatives including coconut oils and shampoos with heat-killed probiotics have shown considerable potential efficacy by replenishing the scalp microbiome.

Central nervous system active medication use in Medicare enrollees receiving home health care: association with chronic pain and anxiety level.

ABSTRACT: No comparative effectiveness data exist on nonopioid analgesics and nonbenzodiazepine anxiolytics to treat pain with anxiety. We examined the relationship between drug class and central nervous system (CNS) active drug polypharmacy on pain and anxiety levels in Medicare enrollees receiving home health (HH) care. This retrospective cohort study included enrollees with diagnoses and 2+ assessments of pain and anxiety between HH admission and discharge. Three sets of linear regression difference-in-reduction analyses assessed the association of pain or anxiety reduction with number of drugs; drug type; and drug combinations in those with daily pain and daily anxiety. Logistic regression analysis assessed the effect of medication number and class on less-than-daily pain or anxiety at HH discharge. A sensitivity analysis using multinomial regression was conducted with a three-level improvement to further determine clinical significance. Of 85,403 HH patients, 43% received opioids, 27% benzodiazepines, 26% gabapentinoids, 32% selective serotonin reuptake inhibitors, and 8% serotonin and norepinephrine reuptake inhibitors (SNRI). Furthermore, 75% had depression, 40% had substance use disorder diagnoses, and 6.9% had PTSD diagnoses. At HH admission, 83%, 35%, and 30% of patients reported daily pain, daily anxiety, and both, respectively. Central nervous system polypharmacy was associated with worse pain control and had no significant effect on anxiety. For patients with daily pain plus anxiety, pain was best reduced with one medication or any drug combination without opioid/benzodiazepine; anxiety was best reduced with combinations other than opiate/benzodiazepine. Gabapentinoids or SNRI achieved clinically meaningful pain control. Selective serotonin reuptake inhibitors provided clinically meaningful anxiety relief.

Innovative approaches to wound healing: insights into interactive dressings and future directions.

The objective of this review is to provide an up-to-date and all-encompassing account of the recent advancements in the domain of interactive wound dressings. Considering the gap between the achieved and desired clinical outcomes with currently available or under-study wound healing therapies, newer more specific options based on the wound type and healing phase are reviewed. Starting from the comprehensive description of the wound healing process, a detailed classification of wound dressings is presented. Subsequently, we present an elaborate and significant discussion describing interactive (unconventional) wound dressings. Latter includes biopolymer-based, bioactive-containing and biosensor-based smart dressings, which are discussed in separate sections together with their applications and limitations. Moreover, recent (2-5 years) clinical trials, patents on unconventional dressings, marketed products, and other information on advanced wound care designs and techniques are discussed. Subsequently, the future research direction is highlighted, describing peptides, proteins, and human amniotic membranes as potential wound dressings. Finally, we conclude that this field needs further development and offers scope for integrating information on the healing process with newer technologies.

Adapting with the Pandemic: Modified Mohs Micrographic Surgery Using Rim and Deep Margin Technique.

The COVID-19 pandemic has changed many facets of medical care and has resulted in a rise in delayed treatments across all specialties, including cosmetic dermatology. Delayed care for squamous cell carcinomas (SCC) and basal cell carcinoma (BCC) is not only a burden for medical providers, but also confers a risk to patients, as delayed surgeries are associated with increased metastatic risk and tumor size. Mohs micrographic surgery (MMS) delayed by more than one year leads to increased risk of complications, including bleeding and impaired wound healing, especially in the elderly population. To decrease bleeding risks, we have developed a modified MMS technique known as the "rim and deep margin" technique. Here, we present additional cases using this technique to minimize bleeding and operative time for patients with an increased risk of morbidity. This technique has been used successfully in the past for large tumors and can now be used for patients who have faced delay of care, as evidenced by its success during the COVID-19 pandemic.

Artificial Intelligence in Dermatology: A Systematic Review of Its Applications in Melanoma and Keratinocyte Carcinoma Diagnosis.

BACKGROUND: Limited access to dermatologic care may pose an obstacle to the early detection and intervention of cutaneous malignancies. The role of artificial intelligence (AI) in skin cancer diagnosis may alleviate potential care gaps. OBJECTIVE: The aim of this systematic review was to offer an in-depth exploration of published AI algorithms trained on dermoscopic and macroscopic clinical images for the diagnosis of melanoma, basal cell carcinoma, and cutaneous squamous cell carcinoma (cSCC). METHODS: Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a systematic review was conducted on peer-reviewed articles published between January 1, 2000, and January 26, 2023. RESULTS AND DISCUSSION: Among the 232 studies in this review, the overall accuracy, sensitivity, and specificity of AI for tumor detection averaged 90%, 87%, and 91%, respectively. Model performance improved with time. Despite seemingly impressive performance, the paucity of external validation and limited representation of cSCC and skin of color in the data sets limits the generalizability of the current models. In addition, dermatologists coauthored only 12.9% of all studies included in the review. Moving forward, it is imperative to prioritize robustness in data reporting, inclusivity in data collection, and interdisciplinary collaboration to ensure the development of equitable and effective AI tools.

Extramammary Paget Disease. Part I. Epidemiology, Pathogenesis, Clinical Features, and Diagnosis.

Extramammary Paget disease (EMPD) is a rare skin cancer of apocrine-rich skin that mimics common inflammatory and infectious dermatoses, leading to delays in diagnosis and increased patient morbidity. Better clinical recognition of this entity, multidisciplinary patient assessment, and deeper understanding of the underlying pathophysiology are essential to improve patient care and disease outcomes. It is important to distinguish primary intraepithelial/micro-invasive EMPD from invasive EMPD or cases with adenocarcinoma arising within EMPD. This 2-part continuing medical education series provides a complete picture of EMPD. Part 1 of this continuing medical education series reviews the epidemiology, oncogenesis, clinical and histopathologic presentation, workup, and prognosis of this rare cancer.

In situ gelling systems for ocular drug delivery.

In situ gelling systems represent a burgeoning paradigm in ocular drug administration, addressing intrinsic challenges posed by extant ocular formulations, such as compromised bioavailability and constraints in traversing the corneal barrier. This systematic review endeavours to comprehensively examine the contemporary landscape of research in this domain, focusing on the nuanced capabilities of in situ gelling systems to optimize drug delivery and enhance therapeutic outcomes, without much technological complexity. Employing a meticulous search strategy across diverse databases for publications and patents spanning the years 2015 to 2023 a total of 26 research papers and 14 patents meeting stringent inclusion criteria were identified. Synthesizing the collective insights derived from these investigations, it becomes evident that in situ gelling systems confer an ability to protract the residence time of formulations or active pharmaceutical ingredients (APIs) within the ocular milieu. This sustained presence engenders extended drug release kinetics, thereby fostering improved patient compliance and mitigating the proclivity for side effects attendant to frequent dosing. These salutary effects extend to diminished systemic drug absorption, augmented ocular bioavailability, and the prospect of reduced dosing frequencies, thereby amplifying patient adherence to therapeutic regimens. Intriguingly, the protective attributes of in situ gelling systems extend to the establishment of an ocular surface barrier, thereby abating the susceptibility to infections and inflammatory responses. In summation, this review underscores the auspicious potential of in situ gelling systems as a transformative approach to advancing ocular drug delivery, warranting sustained research endeavours and developmental initiatives for the betterment of global patient outcomes.

Jet-injection assisted photodynamic therapy for superficial and nodular basal cell carcinoma: A pilot study.

BACKGROUND: Photodynamic therapy (PDT) with topical δ-Aminolevulinic acid (ALA) has efficacy in treating basal cell carcinoma (BCC) but is limited by incomplete penetration of ALA into the deeper dermis. This prospective open-label pilot trial investigated the safety and efficacy of photosensitizer jet injection for PDT (JI-PDT) for BCC treatment. It was performed with 15 patients (n = 15) with histologically confirmed, untreated, low-risk nodular BCCs at a single institution. METHODS: For the intervention, JI-PDT patients (n = 11) received two sessions of jet-injected ALA with PDT separated by four to 6 weeks. To further understand treatment technique, another group of patients (n = 4) received jet-injected ALA followed by tumor excision and fluorescence microscopy (JI-E). Treatment tolerability was assessed by local skin responses (LSR) score at five distinct time intervals. Fluorescence microscopy assessed protoporphyrin IX penetration depth and biodistribution within the tumor. At the primary endpoint, tumor clearance was evaluated via visual inspection, dermoscopy and reflectance confocal microscopy. Postinjection and postillumination pain levels, and patient satisfaction, were scored on a 0-10 scale. RESULTS: Fifteen participants with mean age of 58.3, who were 15/15 White, non-Hispanic enrolled. The median composite LSR score immediately after JI-PDT was 5 (interquartile range [IQR] = 3) which decreased to 0.5 (IQR = 1) at primary endpoint (p < 0.01). Immunofluorescence of excised BCC tumors with jet-injected ALA showed photosensitizer penetration into papillary and reticular dermis. Of the 13 JI-PDT tumors, 11 had tumor clearance confirmed, 1 recurred, and 1 was lost to follow-up. 1/11 patients experienced a serious adverse event of cellulitis. 70% of patients had local scarring at 3 months. Patients reported an average pain level of 5.6 (standard deviation [SD] = 2.3) during jet injection and 3.7 (SD = 1.8) during light illumination. CONCLUSIONS: Jet injection of ALA for PDT treatment of nodular low-risk BCC is tolerable and feasible and may represent a novel modality to improve PDT.

Aetiology and predictors of major bleeding events in patients with heart failure with reduced ejection fraction undergoing percutaneous coronary intervention.

OBJECTIVES: We sought to determine the relationship between the degree of left ventricular ejection fraction (LVEF) impairment and the frequency and type of bleeding events after percutaneous coronary intervention (PCI). DESIGN: This was an observational retrospective cohort analysis. Patients who underwent PCI from 2009 to 2017 were identified from our institutional National Cardiovascular Disease Registry (NCDR) CathPCI database. Patients were stratified by pre-PCI LVEF: preserved (≥50%), mildly reduced (41%-49%) and reduced (≤40%) LVEF. PRIMARY OUTCOME MEASURES: The outcome was major bleeding, defined by NCDR criteria. Events were classified based on bleeding aetiology and analysed by multivariable logistic regression. RESULTS: Among 13 537 PCIs, there were 817 bleeding events (6%). The rate of bleeding due to any cause, blood transfusion, gastrointestinal bleeding and coronary artery perforation or tamponade each increased in a stepwise fashion comparing preserved, mildly reduced and reduced LVEF reduction (p<0.05 for all comparisons). However, there were no differences in bleeding due to asymptomatic drops in haemoglobin, access site haematoma or retroperitoneal bleeding. After multivariable adjustment, mildly reduced and reduced LVEF remained independent predictors of bleeding events (OR 1.36, 95% CI 1.06 to 1.74, p<0.05 and OR 1.73, 95% CI 1.45 to 2.06, p<0.0001). CONCLUSIONS: The degree of LV dysfunction is an independent predictor of post-PCI major bleeding events. Patients with mildly reduced or reduced LVEF are at greatest risk of post-PCI bleeding, driven by an increased need for blood transfusion, major GI bleeding events and coronary artery perforation or tamponade. Pre-PCI LV dysfunction does not predict asymptomatic declines in haemoglobin, access site haematoma or retroperitoneal bleeding.

Extramammary Paget Disease. Part II. Evidence-based Approach to Management.

Extramammary Paget disease is a rare cutaneous malignancy that most commonly affects the genitals, perianal area, and axilla of elderly patients. Delays in care often lead to high levels of disease burden for patients. Thus, evidence-based recommendations are paramount in mitigating morbidity and mortality for this unique patient population. This 2-part continuing medical education series provides a complete picture of extramammary Paget disease. Part 2 of this continuing medical education series focuses on the complex management of extramammary Paget disease including surgical and non-invasive therapies, as well as novel approaches for advanced disease.

Metabolic disruptions and impaired reproductive fitness in wild-caught freshwater turtles (Emydura macquarii macquarii) exposed to elevated per- and polyfluoroalkyl substances (PFAS).

Per- and poly-fluoroalkyl substances (PFAS) pose a threat to organisms and ecosystems due to their persistent nature. Ecotoxicology endpoints used in regulatory guidelines may not reflect multiple, low-level but persistent stressors. This study examines the biological effects of PFAS on Eastern short-necked turtles in Queensland, Australia. In this study, blood samples were collected and analysed for PFAS, hormone levels, and functional omics endpoints. High levels of PFAS were found in turtles at the impacted site, with PFOS being the dominant constituent. The PFAS profiles of males and females differed, with males having higher PFAS concentrations. Hormone concentrations differed between impacted and reference sites in male turtles, with elevated testosterone and corticosterone indicative of stress. Further, energy utilisation, nucleotide synthesis, nitrogen metabolism, and amino acid synthesis were altered in both male and female turtles from PFAS-impacted sites. Both sexes show similar metabolic responses to environmental stressors from the PFAS-contaminated site, which may adversely affect their reproductive fitness. Purine metabolism, caffeine metabolism, and ferroptosis pathway changes in turtles can cause gout, cell death, and overall health problems. Further, the study showed that prolonged exposure to elevated PFAS levels in the wild could compromise turtle reproductive fitness by disrupting reproductive steroids and metabolic pathways.

Aligning patient values and code status: Choice of Diction's Effect (CODE) study.

BACKGROUND: Decisions regarding resuscitation after cardiac arrest are critical from ethical, patient satisfaction, outcome, and healthcare cost standpoints. Physician-reported discussion barriers include topic discomfort, fear of time commitment, and difficulty articulating end-of-life concepts. The influence of language used in these discussions has not been tested. This study explored whether utilizing the alternate term "allow (a) natural death" changed code status decisions in hospitalized patients versus "do not resuscitate" (DNR). METHODS: All patients age 65 and over admitted to a general medicine hospital teaching service were screened (English-speaking, not ICU-level care, no active psychiatric illness, no substance misuse, no active DNR). Participants were randomized to resuscitation discussions with either DNR or "allow natural death" as the "no code" phrasing. Outcomes included patient resuscitation decision, satisfaction with and duration of the conversation, and decision correlation with illness severity and predicted resuscitation success. RESULTS: 102 participants were randomized to the "allow natural death" (N = 49) or DNR (N = 53) arms. The overall "no code" rate for our sample of hospitalized general medicine inpatients age >65 was 16.7%, with 13% in the DNR and 20.4% in the "allow natural death" arms (p = 0.35). Discussion length was similar in the DNR and "allow natural death" arms (3.9 + 3.2 vs. 4.9 + 3.9 minutes), and not significantly different (p = 0.53). Over 90% of participants were highly satisfied with their code status decision, without difference between arms (p = 0.49). CONCLUSIONS: Participants' code status discussions did not differ in "no code" rate between "allow natural death" and DNR arms but were short in length and had high patient satisfaction. Previously reported code status discussion barriers were not encountered. It is appropriate to screen code status in all hospitalized patients regardless of phrasing used.

A deep patient-similarity learning framework for the assessment of diastolic dysfunction in elderly patients.

AIMS: Age-related changes in cardiac structure and function are well recognized and make the clinical determination of abnormal left ventricular (LV) diastolic dysfunction (LVDD) particularly challenging in the elderly. We investigated whether a deep neural network (DeepNN) model of LVDD, previously validated in a younger cohort, can be implemented in an older population to predict incident heart failure (HF). METHODS AND RESULTS: A previously developed DeepNN was tested on 5596 older participants (66-90 years; 57% female; 20% Black) from the Atherosclerosis Risk in Communities Study. The association of DeepNN predictions with HF or all-cause death for the American College of Cardiology Foundation/American Heart Association Stage A/B (n = 4054) and Stage C/D (n = 1542) subgroups was assessed. The DeepNN-predicted high-risk compared with the low-risk phenogroup demonstrated an increased incidence of HF and death for both Stage A/B and Stage C/D (log-rank P < 0.0001 for all). In multi-variable analyses, the high-risk phenogroup remained an independent predictor of HF and death in both Stages A/B {adjusted hazard ratio [95% confidence interval (CI)] 6.52 [4.20-10.13] and 2.21 [1.68-2.91], both P < 0.0001} and Stage C/D [6.51 (4.06-10.44) and 1.03 (1.00-1.06), both P < 0.0001], respectively. In addition, DeepNN showed incremental value over the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) guidelines [net re-classification index, 0.5 (CI 0.4-0.6), P < 0.001; C-statistic improvement, DeepNN (0.76) vs. ASE/EACVI (0.70), P < 0.001] overall and maintained across stage groups. CONCLUSION: Despite training with a younger cohort, a deep patient-similarity-based learning framework for assessing LVDD provides a robust prediction of all-cause death and incident HF for older patients.

A critical role for Macrophage-derived Cysteinyl-Leukotrienes in HIV-1 induced neuronal injury.

Macrophages (MΦ) infected with human immunodeficiency virus (HIV)-1 or activated by its envelope protein gp120 exert neurotoxicity. We found previously that signaling via p38 mitogen-activated protein kinase (p38 MAPK) is essential to the neurotoxicity of HIVgp120-stimulated MΦ. However, the associated downstream pathways remained elusive. Here we show that cysteinyl-leukotrienes (CysLT) released by HIV-infected or HIVgp120 stimulated MΦ downstream of p38 MAPK critically contribute to neurotoxicity. SiRNA-mediated or pharmacological inhibition of p38 MAPK deprives MΦ of CysLT synthase (LTC4S) and, pharmacological inhibition of the cysteinyl-leukotriene receptor 1 (CYSLTR1) protects cerebrocortical neurons against toxicity of both gp120-stimulated and HIV-infected MΦ. Components of the CysLT pathway are differentially regulated in brains of HIV-infected individuals and a transgenic mouse model of NeuroHIV (HIVgp120tg). Moreover, genetic ablation of LTC4S or CysLTR1 prevents neuronal damage and impairment of spatial memory in HIVgp120tg mice. Altogether, our findings suggest a novel critical role for cysteinyl-leukotrienes in HIV-associated brain injury.

Current Landscape of Hyaluronic Acid Filler Use in the United States.

BACKGROUND: Hyaluronic acid (HA) fillers are among the most used fillers for soft-tissue augmentation. There are now many FDA-approved HA products, and the successful use of injectable HA fillers requires an understanding of the available options.  Objective: The purpose of this manuscript is to provide a comprehensive list of HA fillers and their indications. An overview of their biochemical properties and formulations will aid dermatologists in appropriate use. METHODS: A comprehensive search of all the FDA-approved dermal fillers was conducted via the FDA "pre-market approval" (PMA) site. Additional details regarding filler properties were obtained using the respective agent's package inserts.  Results: A total of 28 HA dermal fillers were identified and key pharmaceutical properties were discussed. These findings will help the physician match the appropriate HA filler with the area that is to be treated.  Conclusion: Understanding the available fillers and their properties can help physicians select the appropriate fillers for more predictable and sustainable results.  J Drugs Dermatol. 2024;23(1):1247-1252.    doi:10.36849/JDD.7858.