Effectiveness of Immune Checkpoint Inhibitor with Anti-PD-1 Monotherapy or in Combination with Ipilimumab in Younger versus Older Adults with Advanced Melanoma.

Background: The majority of melanoma is diagnosed in individuals between 55 and 84 years old. Current data varied in reporting differences in survival outcomes amongst different age groups. Methods: A retrospective, multi-center, provincial cohort database was used to investigate the relationship between age (<65 or ≥65 years old) and overall survival. Patients must have had histologically confirmed locally advanced or metastatic melanoma and had to have received at least one cycle of immunotherapy (single agent nivolumab, pembrolizumab, or combination ipilimumab plus nivolumab). Results: From August 2013 to May 2020, we identified 497 patients (median age = 64 [range 12-96 years]; 65.2% men; 36.4% with a BRAF mutation (V600E and V600K)). Of these, 260 were < 65 years old, and 237 were ≥65 years old. A total of 39.1% of the patients in the younger cohort received combination ICI compared with 10.2% in the older cohort, and the difference was statistically significant. Median survival amongst individuals aged ≥65 years old was shorter compared to individuals <65 years old, with a median overall survival of 17.1 (95% CI 12.3-22.9 months) months and 22.2 months (95% CI 18.7-33.8 months), respectively (p = 0.04), at a median follow-up of 34.4 months (range: 1.84-81.4 months). The survival difference was present in the cutaneous melanoma cohort where median OS was 18.2 months (95% CI 12.3-30.4 months) in patients ≥65 years old and 23.8 months (95% CI 19.2-48.2 months) in patients <65 years old, p = 0.04. There were no significant differences by age in the non-cutaneous melanoma cohort. A combination of nivolumab plus ipilimumab was associated with an improved overall survival hazard ratio of 0.48 (95% CI 0.36-0.65) as compared to anti-PD-1 monotherapy alone (p < 0.001). In the cutaneous cohort treated with anti-PD-1 monotherapy (n = 306), no significant differences were seen with median OS at 16.1 months (95% CI 11.4-25.7 months) in patients ≥65 years old and 17.1 months (95% CI 12.0-22.2 months) in patients <65 years old (p = 0.84). Tumor response to anti-PD-1 was higher in the older patients compared with the response in younger patients with cutaneous melanoma. Conclusions: Older melanoma patients have similar survival compared with younger patients after receiving the same treatment with anti-PD-1 monotherapy. The superior survival observed in the younger patients is possibly related to the higher utilization of combination ICI. Tumor response to immunotherapy is superior in older patients with cutaneous melanoma; however, younger patients may improve their survival by using combination ICI.

Topical Clascoterone for Acne Vulgaris.

The pathogenesis of acne is multifactorial and involves inflammation, bacterial dysbiosis, and androgen stimulation. Existing systemic therapies target hormonal pathways to mitigate acne lesions; however, their use is limited to the female population and associated with systemic adverse effects. Clascoterone is the first topical therapy to target the hormonal pathogenesis of acne approved to treat acne vulgaris. In two identical phase 3 trials, clascoterone showed favorable efficacy over placebo in treating acne, with higher treatment success and a greater reduction in acne lesions. Large scale trials are required to assess the efficacy of clascoterone against its comparators and in combination with existing acne therapies; however, results from the current phase 3 trials support the therapeutic value of clascoterone, suggesting that this novel topical androgen inhibitor represents a valuable addition to the catalogue of acne therapy.

The treatment and management of atopic dermatitis in the pediatric emergency department: Highlighting physician practices and the desire for patient-centered resources.

Atopic dermatitis is a common, complex skin disorder with significant morbidity. The management of atopic dermatitis is multifactorial and often varies by physician experience and comfort level. We conducted a single-institution survey of pediatric emergency medicine physicians regarding their perceived confidence in managing atopic dermatitis, knowledge of treatment options, and interest in patient-centered clinical resources. The results of our survey suggest that many pediatric emergency physicians at our center are somewhat confident managing atopic dermatitis and that topical corticosteroids represent the mainstay of treatment of AD. Our survey identified common AD therapies used by emergency department physicians and highlights the desire for further patient-centered resources in the emergency care setting.

Association between Prurigo Nodularis and Etiologies of Peripheral Neuropathy: Suggesting a Role for Neural Dysregulation in Pathogenesis.

Background: Prurigo nodularis (PN) is an intensely pruritic skin condition of considerable morbidity. However, the pathogenesis of PN and its association with underlying neuropathy is unclear. Objective: We sought to investigate the association between PN and etiologies of peripheral neuropathy. Methods: A cross-sectional analysis of adult patients (≥18-year-old) with PN, AD, and Psoriasis at the Johns Hopkins Health System over a six-year period (January 2013-January 2019) was performed. The strength of association with etiologies of peripheral neuropathy were compared to a control cohort of individuals without PN, as well as those with AD or psoriasis. Results: A total of 1122 patients with PN were compared to 10,390 AD patients, 15,056 patients with psoriasis, and a control cohort of 4,949,017 individuals without PN, with respect to 25 comorbidities associated with peripheral neuropathies. Limitations: Comparisons between peripheral neuropathies and PN represent associations but are not causal relationships. Conclusion: Prurigo nodularis is strongly associated with peripheral neuropathies, suggesting a role for neural dysregulation in pathogenesis.

The emerging utility of the cutaneous microbiome in the treatment of acne and atopic dermatitis.

The cutaneous microbiome has potential for therapeutic intervention in inflammatory-driven skin disease. Research into atopic dermatitis and acne vulgaris has highlighted the importance of the skin microbiota in disease pathogenesis, prognostication, and targets for therapeutic intervention. Current management of these conditions aims to control the inflammatory response thought to be associated with specific pathogens using both topical and systemic antimicrobials. However, commensal microbiota found naturally on the skin have been shown to play an important role in the resolution of disease flares. Although often efficacious, the mainstay treatments are not without adverse effects and raise concerns regarding the development of antimicrobial resistance. Augmentation of microbial communities with targeted biotherapy could revolutionize the way inflammatory conditions of the skin are treated. Herein, we review evidence for the role of the cutaneous microbiome in atopic dermatitis and acne vulgaris and suggest that these conditions highlight the potential for microbiome-directed therapeutics.

Scratching the Surface: A Review of Dermatitis.

GENERAL PURPOSE: To present a case-based review illustrating atopic and contact dermatitis, including management of these conditions using topical and systemic therapies. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant should be better able to:1. Review the prevalence, etiology, and consequences of the various types of dermatitis.2. Describe the clinical manifestations and differential diagnosis of the various types of dermatitis.3. Outline the treatment options for the various types of dermatitis. ABSTRACT: Eczematous reactions such as atopic dermatitis and contact dermatitis are prevalent worldwide. Despite contrasting pathophysiology, the diagnosis and management of these dermatitides can be challenging for healthcare providers. Differences in the distribution of the affected areas, duration of onset, and associated symptoms may help to distinguish these conditions. Diagnosis of the respective conditions is useful in developing appropriate management plans. Herein, the authors present a case-based review illustrating these different disease entities. Management of these conditions, including the use of topical and systemic therapies, is discussed.

Diagnosis and Management of Cutaneous Tinea Infections.

GENERAL PURPOSE: To provide information about the epidemiology, clinical features, and management of cutaneous tinea infections. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After completing this continuing education activity, you should be better able to:1. Summarize the epidemiology related to cutaneous tinea infections.2. Describe the clinical features of cutaneous tinea infections.3. Identify features related to the diagnosis and management of cutaneous tinea infections. ABSTRACT: Dermatophyte or tinea infection refers to a group of superficial fungal infections of the hair, skin, and nails. Tinea infections are most commonly caused by fungi of the genus Trichophyton, Microsporum, or Epidermophyton. Cutaneous manifestations of tinea infections are seen worldwide and classified based on the affected body site. The diagnosis of these conditions is complicated by morphologic variations in presentation and overlap with other common infectious and noninfectious entities. As a result, diagnosis and appropriate management of these conditions are essential to avoid patient morbidity. This case-based review summarizes the epidemiology, relevant clinical features, microbiology, and management considerations for commonly encountered tinea infections.

Epidemiology and natural history of Pseudomonas aeruginosa airway infections in non-cystic fibrosis bronchiectasis.

The natural history and epidemiology of Pseudomonas aeruginosa infections in non-cystic fibrosis (non-CF) bronchiectasis is not well understood. As such it was our intention to determine the evolution of airway infection and the transmission potential of P. aeruginosa in patients with non-CF bronchiectasis. A longitudinal cohort study was conducted from 1986-2011 using a biobank of prospectively collected isolates from patients with non-CF bronchiectasis. Patients included were ≥18 years old and had ≥2 positive P. aeruginosa cultures over a minimum 6-month period. All isolates obtained at first and most recent clinical encounters, as well as during exacerbations, that were morphologically distinct on MacConkey agar were genotyped by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). A total of 203 isolates from 39 patients were analysed. These were compared to a large collection of globally epidemic and local CF strains, as well as non-CF isolates. We identified four patterns of infection in non-CF bronchiectasis including: 1) persistence of a single strain (n=26; 67%); 2) strain displacement (n=8; 20%); 3) temporary disruption (n=3; 8%); and 4) chaotic airway infection (n=2; 5%). Patterns of infection were not significant predictors of rates of lung function decline or progression to end-stage disease and acquisition of new strains did not associate with the occurrence of exacerbations. Rarely, non-CF bronchiectasis strains with similar pulsotypes were observed in CF and non-CF controls, but no CF epidemic strains were observed. While rare shared strains were observed in non-CF bronchiectasis, whole-genome sequencing refuted patient-patient transmission. We observed a higher incidence of strain-displacement in our patient cohort compared to those observed in CF studies, although this did not impact on outcomes.

Virulence adaptations of Pseudomonas aeruginosa isolated from patients with non-cystic fibrosis bronchiectasis.

Pseudomonas aeruginosa is a major pathogen in chronic lung diseases such as cystic fibrosis (CF) and non-cystic fibrosis bronchiectasis (nCFB). Much of our understanding regarding infections in nCFB patients is extrapolated from findings in CF with little direct investigation on the adaptation of P. aeruginosa in nCFB patients. As such, we investigated whether the adaptation of P. aeruginosa was indeed similar between nCFB and CF. From our prospectively collected biobank, we identified 40 nCFB patients who had repeated P. aeruginosa isolates separated by ≥6 months and compared these to a control population of 28 CF patients. A total of 84 nCFB isolates [40 early (defined as the earliest isolate in the biobank) and 41 late (defined as the last available isolate in the biobank)] were compared to 83 CF isolates (39 early and 44 late). We assessed the isolates for protease, lipase and elastase production; mucoid phenotype; swarm and swim motility; biofilm production; and the presence of the lasR mutant phenotype. Overall, we observed phenotypic heterogeneity in both nCFB and CF isolates and found that P. aeruginosa adapted to the nCFB lung environment similarly to the way observed in CF isolates in terms of protease and elastase expression, motility and biofilm formation. However, significant differences between nCFB and CF isolates were observed in lipase expression, which may allude to distinct characteristics found in the lung environment of nCFB patients. We also sought to determine virulence potential over time in nCFB P. aeruginosa isolates and found that virulence decreased over time, similar to CF.