Noninvasive Analysis of Peptidoglycan from Living Animals.

The role of the intestinal microbiota in host health is increasingly revealed in its contributions to disease states. The host-microbiome interaction is multifactorial and dynamic. One of the factors that has recently been strongly associated with host physiological responses is peptidoglycan from bacterial cell walls. Peptidoglycan from gut commensal bacteria activates peptidoglycan sensors in human cells, including the nucleotide-binding oligomerization domain-containing protein 2. When present in the gastrointestinal tract, both the polymeric form (sacculi) and depolymerized fragments can modulate host physiology, including checkpoint anticancer therapy efficacy, body temperature and appetite, and postnatal growth. To utilize this growing area of biology toward therapeutic prescriptions, it will be critical to directly analyze a key feature of the host-microbiome interaction from living hosts in a reproducible and noninvasive way. Here we show that metabolically labeled peptidoglycan/sacculi can be readily isolated from fecal samples collected from both mice and humans. Analysis of fecal samples provided a noninvasive route to probe the gut commensal community including the metabolic synchronicity with the host circadian clock. Together, these results pave the way for noninvasive diagnostic tools to interrogate the causal nature of peptidoglycan in host health and disease.

The External Oblique Intercostal Block: Anatomic Evaluation and Case Series.

STUDY OBJECTIVE: We report a modified block technique aimed at obtaining upper midline and lateral abdominal wall analgesia: the external oblique intercostal (EOI) block. DESIGN: A cadaveric study and retrospective cohort study assessing the potential analgesic effect of the EOI block. SETTING: Cadaver lab and operating room. PATIENTS: Two unembalmed cadavers and 22 patients. INTERVENTIONS: Bilateral ultrasound-guided EOI blocks on cadavers with 29 mL of bupivacaine 0.25% with 1 mL of India ink; single-injection or continuous EOI blocks in patients. MEASUREMENTS: Dye spread in cadavers and loss of cutaneous sensation in patients. MAIN RESULTS: In the cadaveric specimens, we identified consistent staining of both lateral and anterior branches of intercostal nerves from T7 to T10. We also found consistent dermatomal sensory blockade of T6-T10 at the anterior axillary line and T6-T9 at the midline in patients receiving the EOI block. CONCLUSIONS: We demonstrate the potential mechanism of this technique with a cadaveric study that shows consistent staining of both lateral and anterior branches of intercostal nerves T7-T10. Patients who received this block exhibited consistent dermatomal sensory blockade of T6-T10 at the anterior axillary line and T6-T9 at the midline. This block can be used in multiple clinical settings for upper abdominal wall analgesia.

A Comparison of Alternative Medicine Users and Non-Users in Patients With Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa patients often seek non-prescription therapies. OBJECTIVE: To determine the prevalence of alternative medicine use and characterize the differences between patients who report using alternative medications versus those who do not. METHODS: We surveyed 67 patients with hidradenitis suppurativa regarding demographics, alternative medicine use, disease severity, and quality of life. RESULTS: 25 (37.2%) of the HS subjects reported alternative medicine use. Alternative medicine users tended to be younger (36.7 vs 40.8 years), have a shorter time since diagnosis (12.6 vs14.6 years), and reported worse quality of life (14.1 vs 11.0) than non-users. These differences were not statistically significant. LIMITATIONS: Limitations included a small sample size. CONCLUSION: Alternative medicine use among patients with hidradenitis is common regardless of disease severity; even mild disease may drive patients to seek alternative treatment. J Drugs Dermatol. 2021;20(10):1072-1074. doi:10.36849/JDD.6046.

The dermatology residency application process.

The dermatology application process is grueling, that is tough to navigate without the proper guidance. This commentary is meant to shed light on the factors that can help applicants stand out in order to be successful in the match. It includes observations from successful applicants from the most recent match process.

Tildrakizumab: A Review of Phase II and III Clinical Trials.

OBJECTIVE: Tildrakizumab, an inhibitor of the p19 subunit of interleukin (IL)-23, was recently Food and Drug Administration (FDA) approved for patients with moderate to severe psoriasis. This article will review the phase II and III clinical trial data of tildrakizumab. DATA SOURCES: A PubMed search from January 2000 to September 2018 was done with the search terms tildrakizumab, guselkumab, risankizumab, p19, interleukin-23, and psoriasis. STUDY SELECTION AND DATA EXTRACTION: Articles discussing phase II and III clinical trial data for tildrakizumab were selected. DATA SYNTHESIS: In phase II and phase III trials, tildrakizumab was safe and efficacious compared with placebo and etanercept. More patients achieved Psoriasis Area and Severity Index 75 receiving tildrakizumab (200 mg, 62%-74%; 100 mg, 61%-66%; 25 mg, 64%; 5 mg, 33%) compared with placebo (4%-6%, P < 0.0001) and etanercept (48%, P = 0.01). More patients achieved Physician Global Assessment (PGA) response of "clear" or "minimal" receiving tildrakizumab (200 mg, 59%; 100 mg, 55%-58%) than the placebo group (4%-7%, P < 0.0001). 59% of patients who received tildrakizumab 200 mg achieved a PGA response of "clear" or "minimal" compared with etanercept (48%, P = 0.0031). The most common adverse effect was infection. Relevance to Patient Care and Clinical Practice: Tildrakizumab is a new, FDA-approved, physician-administered biological therapy for patients with moderate to severe psoriasis. It appears to be efficacious and safe so far. CONCLUSION: Tildrakizumab is efficacious and safe for the treatment of patients with moderate to severe psoriasis. IL-23/p19 inhibitors are a promising class of biological therapy.

Review of future insights of Dragon's Blood in dermatology.

To assess the possible clinical implication of Dragon's Blood in dermatology, a PubMed search was conducted using the keyword "Dragon's Blood," "Croton lechleri," and more. Dragon's Blood from C. lechleri is an Amazonian medicinal plant with a characteristic red sap. Its array of phytochemical action in preclinical studies include anti-inflammatory, antioxidant, antimicrobial, antifungal, and antineoplastic properties. Clinical studies reflect wound healing and antiviral properties. Although its popularity is rising in western medicine, C. lechleri offers limited use in dermatology and further investigation is necessary to gain further insight into its potential clinical implication.

Prescribing Patterns for Atopic Dermatitis in the United States

Introduction: Introduction: Although future atopic dermatitis (AD) clinical research is intended to improve standard-of-care treatment, how patients are currently treated is not well characterized. The purpose of this study was to determine the most frequent medications prescribed in all ages of AD. Methods: The National Ambulatory Medical Care Survey (NAMCS) is a nationally representative survey of United States office-based ambulatory visits and records demographics, diagnoses, and treatments. This is a cross-sectional study using the NAMCS of all AD outpatient office visits from 2006 to 2015. Patient visits with an ICD-9-CM code for AD (691.8) were collected and analyzed. Frequency tables were created for age, race, providers managing AD, and treatment. Results: Patient demographics of AD visits included 51% male (95% Confidence Interval [CI]: 44-58%), 71% white (65-77%), 19% African American (14-25%), and 10% Asian (6-14%). About 31% (24-37%) of visits were to pediatricians and 27% (22-33%) to dermatologists whereas per physician, dermatologists managed more AD visits than pediatricians. Topical corticosteroids (59%; 52-66%) were the most common class of medications prescribed followed by antibiotics (11%; 6-16%) and second generation antihistamines (6%; 3-10%). The most common topical corticosteroid prescribed in AD was triamcinolone (25% of office visits; 18-31%). Hydrocortisone was the most common topical corticosteroid prescribed to children <1 year of age and children aged 8 to 18, whereas triamcinolone was more common in children 2 to 7 years and adults >18 years. Discussion: Topical corticosteroids were the most frequent prescriptions provided at office-based ambulatory visits whereas antibiotics and second-generation antihistamines were the second and third most common prescribed medications, respectively. Although pediatricians manage more AD visits than dermatologists in total visits, dermatologists manage more AD visits than pediatricians per physician. Characterizing how AD patients are currently treated may build a reference for future clinical research investigating novel standard-of-care treatment in AD. J Drugs Dermatol. 2019;18(10):987-990.

Validation of a Hidradenitis Suppurativa Self-Assessment Tool.

BACKGROUND: Hidradenitis suppurativa (HS) is a debilitating dermatologic condition presenting with recurrent abscesses. While there are multiple scales to determine HS severity, none are designed for self-administration. A validated severity self-assessment tool may facilitate survey research and improve communication by allowing patients to objectively report their HS severity between clinic visits. OBJECTIVES: The purpose of this study was to assess a self-administered HS measure. METHODS: An HS self-assessment tool (HSSA) with 10 photographs of different Hurley stages was developed. The tool was administered to patients diagnosed with HS who visited the Wake Forest Baptist Health dermatology clinic over a span of 2 months. Physician-administered Hurley stage was recorded to determine criterion validity. To assess test-retest reliability of the measure, patients completed the HSSA again at least 30 minutes after the first completion. RESULTS: Twenty-four patients completed the measure, and 20 of these patients completed it twice. Agreement between physician-determined Hurley stage and self-determined Hurley stage was 66.7% with a weighted kappa of 0.57 (95% confidence interval [CI]: 0.30-0.84). The weighted kappa for agreement between patients' initial and second completion of the HSSA was 0.81 (95% CI: 0.64-0.99). CONCLUSIONS: The self-administered measure provides moderate agreement with physician-determined Hurley stage and good test-retest reliability.

Diet and psoriasis.

BACKGROUND: Patients with psoriasis have a growing interest in managing their disease through diet. OBJECTIVE: This review paper aims to analyze dietary interventions for psoriasis and their outcome. METHODS: Terms "psoriasis AND diet" were used to search PubMed database and 63 articles describing dietary changes influencing psoriasis were selected. RESULTS: Low calorie diet (LCD) improves Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) in conjunction with topical or systemic therapy, although LCD was unsuccessful in maintaining disease remission when patients discontinued concomitant cyclosporine or methotrexate therapy. A fish oil diet improved baseline PASI of 7.7 to 5.3 at three months and 2.6 at 6 months compared to control (PASI: 8.9, 7.8, and 7.8, respectively). A randomized, double-blind, placebo-controlled study investigating selenium supplementation in psoriasis provided no PASI improvement. Zinc supplementation with concomitant betamethasone valerate 0.0025% ointment in a randomized, double-blind, placebo-controlled study provided a mean PASI of 11.2 in the intervention group and 8.0 in the control group with no significant difference between both arms. Gluten free diet and vitamin D supplementation were also efficacious dietary changes although results were mixed. CONCLUSIONS: Dietary changes alone do not cause a large effect in psoriasis but may become an important adjunct to current first line treatments.

A review of topical corticosteroid sprays for the treatment of inflammatory dermatoses.

BACKGROUND: Topical corticosteroids are available in many vehicles. However, patients' preference for vehicles are variable and could be tailored to maximize patient adherence. Spray vehicles may offer, convenience, and strong efficacy. METHODS: A literature review was conducted using keywords: clobetasol, desoximetasone, betamethasone, triamcinolone, corticosteroid, topical, spray, vehicles, treatment, and clinical trial. RESULTS: For moderate-to-severe plaque psoriasis, 87% of subjects achieved an Overall Disease Severity (ODS) Score ≤2 at week two and 78% achieved an ODS ≤1 after four weeks with clobetasol propionate (CP) 0.05% spray compared to 17% and 3% in the control group, respectively (P<0.001). For desoximetasone 0.25% spray, 31%-53% with moderate-to-severe psoriasis achieve Physician's Global Assessment (PGA) score ≤1 at day 28 versus 5%-18% in the vehicle spray group (P<0.01). For betamethasone dipropionate 0.05% spray, 19% with mild-to-moderate plaque psoriasis achieved an Investigator's Global Assessment (IGA) score ≤1 or a 2-grade reduction in IGA versus 2.3% in vehicle group (P≤0.001). For mild-to-severe steroid responsive inflammatory dermatoses, 64% using triamcinolone acetonide 0.2% spray achieved clear or almost clear skin at day 14 (no P value reported). Adverse events including burning, irritation, and dryness were similar across all corticosteroids.

Injectate spread following anterior sub-costal and posterior approaches to the quadratus lumborum block: A comparative cadaveric study.

BACKGROUND: The dermatomal level of analgesia achieved with quadratus lumborum blocks varies according to the location of injection. The most commonly used approaches are either at the postero-lateral aspect or anterior to the quadratus lumborum muscle. OBJECTIVE: To determine whether the site of injection of contrast dye around the quadratus lumborum muscle of cadavers affects the extent and mechanism of dye spread. DESIGN: Observational human cadaver study. SETTING: Cleveland Clinic cadaveric laboratory. PARTICIPANTS: Six fresh human cadavers. INTERVENTIONS: The cadavers received either a posterior quadratus lumborum block or an anterior subcostal quadratus lumborum block on each side. MAIN OUTCOME MEASURES: Cadavers were dissected to determine the extent of dye spread. RESULTS: The posterior quadratus lumborum block approach revealed consistently deep staining of the iliohypogastric, ilioinguinal, subcostal nerve, T11 to 12 and L1 nerve roots. In addition, staining of the middle thoracolumbar fascia was seen in all specimens but only variable staining of T10 nerve roots. The anterior subcostal quadratus lumborum block approach in all specimens demonstrated predictable deep staining of the iliohypogastric and ilioinguinal nerves, subcostal nerves, T11 to 12 and L1 nerve roots, and in addition traversing the arcuate ligaments to involve T9 to 12 nerve roots with variable staining of higher thoracic nerve roots. CONCLUSIONS: Our cadaveric study demonstrates that injection of dye on the posterior aspect of quadratus lumborum muscle led to injectate spread through the lateral and posterior abdominal wall but with limited cranial spread, whereas the anterior approach produced broader coverage of the lower to mid-thoracic region. Clinical translation of these findings to determine the practical significance is warranted.

Role of Effective Policy and Screening in Managing Pediatric Nutritional Insecurity as the Most Important Social Determinant of Health Influencing Health Outcomes.

Social Determinants of Health (SDOH) impact nearly half of health outcomes, surpassing the influence of human behavior, clinical care, and the physical environment. SDOH has five domains: Economic Stability, Education Access and Quality, Health Care Access and Quality, Neighborhood and Built Environment, and Social and Community Context. Any adversity arising out of these interlinked domains predominantly affects children due to their greater susceptibility, and the adverse outcomes may span generations. Unfavorable SDOH may cause food insecurity, malnutrition, unbalanced gut microbiome, acute and chronic illnesses, inadequate education, unemployment, and lower life expectancy. Systematic screening by health care workers and physicians utilizing currently available tools and questionnaires can identify children susceptible to adverse childhood experiences, but there is a deficiency with respect to streamlined approach and institutional support. Additionally, current ameliorating supplemental food programs fall short of pediatric nutritional requirements. We propose a nutrition-based Surveillance, Screening, Referral, and Reevaluation (SSRR) plan encompassing a holistic approach to SDOH with a core emphasis on food insecurity, coupled with standardizing outcome-based interventions. We also propose more inclusive use of Food Prescription Programs, tailored to individual children's needs, with emphasis on education and access to healthy food.

Non-invasive Analysis of Peptidoglycan from Living Animals.

The role of the intestinal microbiota in host health is increasingly revealed in its contributions to disease states. The host-microbiome interaction is multifactorial and dynamic. One of the factors that has recently been strongly associated with host physiological responses is peptidoglycan from bacterial cell walls. Peptidoglycan from gut commensal bacteria activate peptidoglycan sensors in human cells, including the Nucleotide-binding oligomerization domain containing protein 2 (NOD2). When present in the gastrointestinal tract, both the polymeric form (sacculi) and de-polymerized fragments can modulate host physiology, including checkpoint anticancer therapy efficacy, body temperature and appetite, and postnatal growth. To leverage this growing area of biology towards therapeutic prescriptions, it will be critical to directly analyze a key feature of the host-microbiome interaction from living hosts in a reproducible and non-invasive way. Here we show that metabolically labeled peptidoglycan/sacculi can be readily isolated from fecal samples collected from both mice and humans. Analysis of fecal samples provided a non-invasive route to probe the gut commensal community including the metabolic synchronicity with the host circadian clock. Together, these results pave the way for non-invasive diagnostic tools to interrogate the causal nature of peptidoglycan in host health and disease.

Gut Microbiota to Microglia: Microbiome Influences Neurodevelopment in the CNS.

The brain is traditionally viewed as an immunologically privileged site; however, there are known to be multiple resident immune cells that influence the CNS environment and are reactive to extra-CNS signaling. Microglia are an important component of this system, which influences early neurodevelopment in addition to modulating inflammation and regenerative responses to injury and infection. Microglia are influenced by gut microbiome-derived metabolites, both as part of their normal function and potentially in pathological patterns that may induce neurodevelopmental disabilities or behavioral changes. This review aims to summarize the mounting evidence indicating that, not only is the Gut-Brain axis mediated by metabolites and microglia throughout an organism's lifetime, but it is also influenced prenatally by maternal microbiome and diet, which holds implications for both early neuropathology and neurodevelopment.

Real-time non-invasive fluorescence imaging of gut commensal bacteria to detect dynamic changes in the microbiome of live mice.

In mammals, gut commensal microbiota interact extensively with the host, and the same interactions can be dysregulated in diseased states. Animal imaging is a powerful technique that is widely used to diagnose, measure, and track biological changes in model organisms such as laboratory mice. Several imaging techniques have been discovered and adopted by the research community that provide dynamic, non-invasive assessment of live animals, but these gains have not been universal across all fields of biology. Herein, we describe a method to non-invasively image commensal bacteria based on the specific metabolic labeling of bacterial cell walls to illuminate the gut bacteria of live mice. This tagging strategy may additionally provide unprecedented insight into cell wall turnover of gut commensals, which has implications for bacterial cellular growth and division, in a live animal.

Reciprocal Interactions Between the Gut Microbiome and Mammary Tissue Mast Cells Promote Metastatic Dissemination of HR+ Breast Tumors.

Establishing commensal dysbiosis, defined as an inflammatory gut microbiome with low biodiversity, before breast tumor initiation, enhances early dissemination of hormone receptor-positive (HR+) mammary tumor cells. Here, we sought to determine whether cellular changes occurring in normal mammary tissues, before tumor initiation and in response to dysbiosis, enhanced dissemination of HR+ tumors. Commensal dysbiosis increased both the frequency and profibrogenicity of mast cells in normal, non-tumor-bearing mammary tissues, a phenotypic change that persisted after tumor implantation. Pharmacological and adoptive transfer approaches demonstrated that profibrogenic mammary tissue mast cells from dysbiotic animals were sufficient to enhance dissemination of HR+ tumor cells. Using archival HR+ patient samples, we determined that enhanced collagen levels in tumor-adjacent mammary tissue positively correlated with mast cell abundance and HR+ breast cancer recurrence. Together, these data demonstrate that mast cells programmed by commensal dysbiosis activate mammary tissue fibroblasts and orchestrate early dissemination of HR+ breast tumors.