Tolerability and Efficacy of Clindamycin/Tretinoin versus Adapalene/Benzoyl Peroxide in the Treatment of Acne Vulgaris.

Acne vulgaris is the most common dermatological disorder worldwide, causing significant physical and psychological morbidity. Topical combination therapy has shown superior efficacy compared to monotherapy, especially when combined with retinoids. Few studies have directly compared combined formulations. This evaluator-blinded pilot study compared the efficacy and tolerability of two marketed topical combination acne gels, clindamycin 1%-tretinoin 0.025% (CT) and benzoyl peroxide 2.5%-adapalene 0.1% (BA) in 20 patients with mild to moderate acne vulgaris. Gels were applied daily on opposite sides of the face for 21 days. The primary outcome was difference in transepidermal water loss (TEWL) at the end of treatment. Secondary endpoints were skin moisture content measurement, Investigators' Global Assessment, subject self-assessments (SSA) of burning/stinging, itching, erythema, and dryness/scaling, and Comparative Participant Satisfaction Questionnaire (CPSQ). Efficacy was assessed by inflammatory and non- inflammatory acne efflorescences counts. TEWL increased significantly for both CT and BA (+57.74%, P=0.002; +58.77%, P<0.001); skin moisture content significantly decreased only for BA (-16.47%, P=0.02). Only BA showed a significant increase in erythema and dryness/scaling (P=0.027 and P=0.014) and in SSA burning/stinging (P=0.04). Patient satisfaction evaluation also reflected the strong BA irritation. Although CT and BA both reduced acne lesions (P<0.001) and more patients preferred to continue with CT, subject perception of acne improvement was higher for BA. These findings suggest that CT and BA have similar efficacy in the treatment of mild to moderate papulopustular acne. However, CT was better tolerated than BA by both medical and subject evaluation. CT is an effective and tolerated treatment option.J Drugs Dermatol. 2021;20(3):295-301. doi:10.36849/JDD.2021.5641.

Occupational allergy to phytase: case series of eight production workers exposed to animal feed additives.

BACKGROUND: In agricultural meat production, adding enzymes such as phytase to animal feed is widespread, but there is little awareness of the allergenic potential and health risks of these fungal enzymes. PATIENTS AND METHODS: We report on eight patients working in a plant producing phytase granulates. All patients complained about work-related rhinitis occurring within six months of the onset of exposure to phytase dust. Asthmatic symptoms and contact urticaria also occurred. To detect sensitizations to phytase, skin prick-, patch-, and basophil activation test were carried out with the factory product. Levels of IgE and IgG against phytase were also measured. RESULTS: There was a positive reaction to phytase with skin prick testing in seven of the eight patients. IgE specific to phytase was detectable in four of the eight patients, and IgG specific to phytase was detectable in six of the eight patients. The basophil activation test was positive in four out of seven patients tested, but the patch test was negative in all patients tested. Transfer to a different workplace with no exposure to phytase completely eliminated the symptoms. CONCLUSIONS: Mold enzymes such as phytase are highly potent occupational allergens. Occupational safety measures must be strictly implemented in order to protect the health of workers.

Impact of radiation, systemic therapy and treatment sequencing on survival of patients with melanoma brain metastases.

BACKGROUND: Combining stereotactic radiosurgery (SRS) and active systemic therapies (STs) achieved favourable survival outcomes in patients with melanoma brain metastases (MBMs) in retrospective analyses. However, several aspects of this treatment strategy remain poorly understood. We report on the overall survival (OS) of patients with MBM treated with a combination of radiotherapy (RT) and ST as well as the impact of the v-Raf murine sarcoma viral oncogene homolog B (BRAF)-V600 mutation (BRAFmut) status, types of RT and ST and their sequence. PATIENTS AND METHODS: Data of 208 patients treated with SRS or whole brain radiation therapy (WBRT) and either immunotherapy (IT) or targeted therapy (TT) within a 6-week interval to RT were analysed retrospectively. OS was calculated from RT to death or last follow-up. Univariate and multivariate Cox proportional hazard analyses were performed to determine prognostic features associated with OS. RESULTS: The median follow-up was 7.3 months. 139 patients received IT, 67 received TT and 2 received IT and TT within 6 weeks to RT (WBRT 45%; SRS 55%). One-year Kaplan-Meier OS rates were 69%, 65%, 33% and 18% (P < .001) for SRS with IT, SRS with TT, WBRT with IT and WBRT with TT, respectively. Patients with a BRAFmut receiving IT combined with RT experienced higher OS rates (88%, 65%, 50% and 18%). TT following RT or started before and continued thereafter was associated with improved median OS compared with TT solely before RT (12.2 [95% confidence interval {CI} 9.3-15.1]; 9.8 [95% CI 6.9-12.6] versus 5.1 [95% CI 2.7-7.5]; P = .03). CONCLUSION: SRS and IT achieved the highest OS rates. A BRAFmut appears to be a favourable prognostic factor for OS. For the combination of RT and TT, the sequence appears to be crucial. Combinations of WBRT and ST achieved unprecedentedly high OS rates and warrant further studies.

Immunomodulatory effects of BRAF and MEK inhibitors: Implications for Melanoma therapy.

Targeted therapy with BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) provides rapid disease control with high response rates in patients with BRAF-mutant metastatic melanoma. However, the majority of patients develop resistance to therapy during the course of therapy. Immune checkpoint inhibitors show a slower onset of action with lower response rates, with responders showing sustained response. The combination of BRAFi/MEKi and immune checkpoint inhibitors combines the hope for a fast, reliable and lasting response to therapy. Preclinical data supports this hypothesis. With the help of the PubMed database, a comprehensive search and analysis of preclinical and clinical studies on the combination of BRAFi/MEKi with immune checkpoint inhibitors was performed and yielded the following results: 1) In vivo, BRAFi and MEKi have no negative effects on immune cells; BRAFi and MEKi generate 2) an immune stimulating tumor microenvironment, 3) an increased infiltration of immune cells into the tumors, 4) a better recognition of melanoma cells by immune effector cells, and 5) a better functionality of the immune effector cells. In addition, in vivo experiments 6) demonstrated a superiority of the combination treatment compared to the individual strategies in both BRAF-mutant and BRAF wild-type melanomas. In summary, available data show that both BRAFi and MEKi have beneficial effects on the antitumor immunity and the tumor microenvironment as a whole, which is mediated by different mechanisms. Currently, clinical studies are underway to investigate combinations of BRAFi and MEKi with immune checkpoint inhibitors. The results of these studies are eagerly awaited.

Melanoma Brain Metastases: Local Therapies, Targeted Therapies, Immune Checkpoint Inhibitors and Their Combinations-Chances and Challenges.

Recent phase II trials have shown that BRAF/MEK inhibitors and immune checkpoint inhibitors are active in patients with melanoma brain metastases (MBM), reporting intracranial disease control rates of 50-75%. Furthermore, retrospective analyses suggest that combining stereotactic radiosurgery with immune checkpoint inhibitors or BRAF/MEK inhibitors prolongs overall survival. These data stress the need for inter- and multidisciplinary cooperation that takes into account the individual prognostic factors in order to establish the best treatment for each patient. Although the management of MBM has dramatically improved, a substantial number of patients still progress and die from brain metastases. Therefore, there is an urgent need for prospective studies in patients with MBM that focus on treatment combinations and sequences, new treatment strategies, and biomarkers of treatment response. Moreover, further research is needed to decipher brain-specific mechanisms of therapy resistance.

Heart rate variability biofeedback therapy and graded exercise training in management of chronic fatigue syndrome: An exploratory pilot study.

OBJECTIVE: Chronic fatigue syndrome (CFS) is characterised by persistent fatigue, exhaustion, and several physical complaints. Research has shown cognitive behavioural therapy (CBT) and graded exercise training (GET) to be the most effective treatments. In a first step we aimed to assess the efficacy of heart rate variability biofeedback therapy (HRV-BF) as a treatment method comprising cognitive and behavioural strategies and GET in the pilot trial. In a second step we aimed to compare both interventions with regard to specific parameters. METHODS: The study was conducted in an outpatient treatment setting. A total of 28 women with CFS (50.3±9.3years) were randomly assigned to receive either eight sessions of HRV-BF or GET. The primary outcome was fatigue severity. Secondary outcomes were mental and physical quality of life and depression. Data were collected before and after the intervention as well as at a 5-month follow-up. RESULTS: General fatigue improved significantly after both HRV-BF and GET. Specific cognitive components of fatigue, mental quality of life, and depression improved significantly after HRV-BF only. Physical quality of life improved significantly after GET. There were significant differences between groups regarding mental quality of life and depression favouring HRV-BF. CONCLUSION: Both interventions reduce fatigue. HRV-BF seems to have additional effects on components of mental health, including depression, whereas GET seems to emphasise components of physical health. These data offer implications for further research on combining HRV-BF and GET in patients with CFS. TRIAL REGISTRATION: The described trial has been registered at the International Clinical Trials Registry Platform following the number DRKS00005445.