Propionibacterium acnes Induces an IL-17 Response in Acne Vulgaris that Is Regulated by Vitamin A and Vitamin D.

Acne vulgaris is the most common skin disorder affecting millions of people worldwide and inflammation resulting from the immune response targeting Propionibacterium acnes has a significant role in its pathogenesis. In this study, we have demonstrated that P. acnes is a potent inducer of T helper 17 (Th17) and Th1, but not Th2 responses in human peripheral blood mononuclear cells (PBMCs). P. acnes stimulated expression of key Th17-related genes, including IL-17A, RORα, RORc, IL-17RA, and IL-17RC, and triggered IL-17 secretion from CD4(+), but not from CD8(+) T cells. Supernatants from P. acnes-stimulated PBMCs were sufficient to promote the differentiation of naive CD4(+)CD45RA T cells into Th17 cells. Furthermore, we found that the combination of IL-1β, IL-6, and transforming growth factor-β-neutralizing antibodies completely inhibited P. acnes-induced IL-17 production. Importantly, we showed that IL-17-expressing cells were present in skin biopsies from acne patients but not from normal donors. Finally, vitamin A (all-trans retinoic acid) and vitamin D (1,25-dihydroxyvitamin D3) inhibited P. acnes-induced Th17 differentiation. Together, our data demonstrate that IL-17 is induced by P. acnes and expressed in acne lesions and that both vitamin A and D could be effective tools to modulate Th17-mediated diseases such as acne

Salivary exRNA biomarkers to detect gingivitis and monitor disease regression

AimThis study tests the hypothesis that salivary extracellular RNA (exRNA) biomarkers can be developed for gingivitis detection and monitoring disease regression.Materials and MethodsSalivary exRNA biomarker candidates were developed from a total of 100 gingivitis and nonâ gingivitis individuals using Affymetrix’s expression microarrays. The top 10 differentially expressed exRNAs were tested in a clinical cohort to determine whether the discovered salivary exRNA markers for gingivitis were associated with clinical gingivitis and disease regression. For this purpose, unstimulated saliva was collected from 30 randomly selected gingivitis subjects, the gingival and plaque indexes scores were taken at baseline, 3 and 6 weeks and salivary exRNAs were assayed by means of reverse transcription quantitative polymerase chain reaction.ResultsEight salivary exRNA biomarkers developed for gingivitis were statistically significantly changed over time, consistent with disease regression. A panel of four salivary exRNAs [SPRR1A, lncâ TET3â 2:1, FAM25A, CRCT1] can detect gingivitis with a clinical performance of 0.91 area under the curve, with 71% sensitivity and 100% specificity.ConclusionsThe clinical values of the developed salivary exRNA biomarkers are associated with gingivitis regression. They offer strong potential to be advanced for definitive validation and clinical laboratory development test.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144647/1/jcpe12930.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144647/2/jcpe12930_am.pd

Total-Body 68Ga-PSMA-11 PET/CT for Bone Metastasis Detection in Prostate Cancer Patients: Potential Impact on Bone Scan Guidelines

Our purpose was to determine the relationship between serum prostate-specific antigen (PSA) level categories (<5, 5-10, 10-20, and >20 ng/mL) and the incidence of bone metastases detected by total-body 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT and to assess if expanding the 68Ga-PSMA-11 PET/CT imaging field to include the vertex and lower extremities (total-body acquisition) affects bone metastasis detection rates and patient management. Methods: This was a retrospective analysis of 388 prostate cancer patients enrolled in 5 prospective studies (NCT02940262, NCT03368547, NCT03042312, NCT04050215, and NCT03515577). All underwent 68Ga-PSMA-11 PET/CT scans acquired from vertex to toes for primary staging (n = 93/388, 24%), biochemical recurrence (BCR) localization (n = 225/388, 58%), or restaging metastatic disease (M1) before or during systemic therapy (n = 70/388, 18%) between September 2017 and May 2018. Results: In total, 321 of 388 patients (83%) had a positive 68Ga-PSMA-11 study. PSMA-positive bone lesions were found in 105 of 388 (27%) patients, with an incidence that was positively associated with serum PSA level (<10 ng/mL, 21%; 10-20 ng/mL, 41%; ≥20 ng/mL, 41%; P < 0.001). This association was maintained for all 3 indications: initial staging, BCR, and restaging M1. Bone metastases occurred most frequently in restaging M1, followed by BCR and initial staging. Bone metastasis incidence was not significantly associated with National Comprehensive Cancer Network risk score (P = 0.22). The average number of PSMA-positive regions also increased with serum PSA level (P < 0.001). Eighteen of 388 (5%) and 18 of 388 (5%) had lesions above the superior orbital ridge and below the proximal third of the femur, respectively. There was only 1 of 388 patients (0.26%) in whom the total-body PET acquisition had an impact on management. Conclusion: Bone metastases as assessed with 68Ga-PSMA-11 PET/CT are prevalent even in patients with low serum PSA levels. Therefore, current guidelines for bone assessments in prostate cancer patients should be revisited because 68Ga-PSMA-11 PET/CT may provide additional information for accurate bone staging at low serum PSA levels. Including the total body (from vertex to toes) in 68Ga-PSMA-11 PET/CT imaging revealed additional bone lesions in 6% of patients, but without significantly affecting patient management

Who Provides Primary Care? An Assessment of HIV Patient and Provider Practices and Preferences.

Non-AIDS co-morbidities are emerging as the main health problems for those living with HIV, and primary care for this population is an evolving challenge. Recent studies have raised the question of whether specialists or generalists are best suited to provide HIV primary care, but patients' actual usage patterns and the preferences of patients and providers have not been well studied. We anonymously surveyed 98 patients and eight HIV-specialized providers regarding primary care usage patterns and preferences at an academic HIV clinic in Los Angeles that serves insured patients. Fifty-nine percent of patients use their HIV physician as their primary care provider, and 84% would prefer this model. Physicians were divided on their preferred role, with five out of eight desiring to provide both primary care and HIV care. All eight physicians rated their comfort with antiretroviral therapy and opportunistic infections greater than for non-AIDS co-morbidities. Eighty-one percent of patients and seven of eight providers were supportive of having a co-located primary care physician at the HIV clinic. We conclude that patients prefer integration of HIV and primary care, but providers have variable desire to serve as primary care physicians and may be uncomfortable with non-AIDS co-morbidities. This raises the need for improved patient-provider communication about primary care needs, and calls for novel ways of systematically providing primary care to HIV-infected patients

Physical and psychosocial comorbidities of pediatric hidradenitis suppurativa: A retrospective analysis

Background/objectivesHidradenitis suppurativa (HS) is understudied in the pediatric population. Adult HS patients are known to have a high comorbidity burden. We aimed to describe physical and psychosocial comorbidities in a cohort of pediatric HS patients.MethodsA retrospective chart review of pediatric HS patients at a single academic institution was conducted. Data on patient demographics, disease characteristics, and physical and psychosocial comorbidities in pediatric patients with HS were collected and analyzed.ResultsSeventy-three pediatric patients were included in this study, 81% female. Mean (SD) age of HS disease onset was 12.6 (2.9) years. Comorbid conditions were reported in 68 of 73 (93%) patients. Significantly increased rates of several comorbidities were seen in our cohort as compared to the general US pediatric population. Metabolic and endocrine abnormalities were prevalent, with 52% (22/42) patients with obesity and 10% (6/59) with polycystic ovary syndrome. The most common cutaneous comorbidity was acne vulgaris, seen in 37% (27/73) of patients. Over one quarter (21/73, 29%) of patients had either an anxiety or depression disorder. Almost one-fifth (14/73, 19%) of our cohort had a diagnosis of asthma and other reactive airway diseases. Only one-third (24/73, 33%) of patients had documentation regarding impact of HS on their daily life. Overall, comorbidities largely did not significantly differ based on race, gender, or disease severity.ConclusionsPediatric patients with HS face a high-comorbidity burden, especially with psychiatric conditions. Early identification, including routine mental health screening, and management of comorbidities is warranted in the pediatric HS population

Opioid prescription patterns among radiation oncologists in the United States.

BackgroundRadiation oncologists (ROs) play an important role in managing cancer pain; however, their opioid prescribing patterns remain poorly described.MethodsThe 2016 Medicare Physician Compare National Downloadable and the 2016 Medicare Part D Prescriber Data files were cross-linked to identify RO-written opioid prescriptions.ResultsOf 4,627 identified ROs, 1,360 (29.3%) wrote >10 opioid prescriptions. The average number of opioid prescriptions written was significantly (P ≤ .05) associated with the following RO characteristics: sex [13.1 ± 36.5 male vs 7.5 ± 16.9 female]; years since medical school graduation [4.5 ± 11.5 1-10 years vs 12.6 ± 26.0 11-24 years vs 13.3 ± 40.9 ≥25 years]; practice size [15.5 ± 44.6 size ≤10 vs 13.3 ± 25.9 size 11-49 vs 8.5 ± 12.7 size 50-99 vs 8.8 ± 26.9 size ≥100]; Medicare Physician Quality Reporting System (PQRS) participation [12.6 ± 31.8 yes vs 7.0 ± 35.4 no]; and practice location [17.4 ± 47.0 South vs 10.6 ± 29.4 Midwest vs 8.1 ± 13.9 West vs 6.9 ± 15.2 Northeast]. On multivariable regression modeling, male sex (RR 1.29, 95% CI 1.22-1.35, P < .001), ≥25 years since graduation (RR 0.78, 95% CI 0.64-0.70, 1-10 years vs ≥25 years; RR 1.00, 95% CI 0.96 - 1.04, 11-24 years vs ≥25 years; P < .001), practice size <10 members (RR 1.51, CI 1.44-1.59, ≤10 vs ≥100 members, RR 1.27, CI 1.20-1.34, 10-49 vs ≥100 members, RR 0.86, CI 0.80-0.92, 50-99 vs ≥100 members, P < .001), PQRS participation (RR 1.12, CI 1.04-1.19, P < .002), and Southern location (RR 0.67, CI 0.64-0.70, Midwest vs South; RR 0.39, CI 0.37-0.41, Northeast vs South; RR 0.43, CI 0.41-0.46, West vs South; P < .001) were predictive of higher opioid prescription rates.ConclusionsFactors associated with increased number of RO-written opioid prescriptions were male sex, ≥25 years since graduation, group practice <10, PQRS participation, and Southern location. Additional research is required to establish optimal opioid prescribing practices for ROs

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