Spin- and angle-resolved photoemission spectroscopy study of heptahelicene layers on Cu(111) surfaces.

It has been demonstrated previously that electrons interact differently with chiral molecules depending on their polarization. For enantiomeric pure monolayers of heptahelicene, opposite asymmetries in spin polarization were reported and attributed to the so-called chirality-induced spin selectivity effect. However, these promising proof-of-concept photoemission experiments lack the angular and energy resolution that could provide the necessary insights into the mechanism of this phenomenon. In order to fill in the missing gaps, we provide a detailed spin- and angle-resolved photoemission spectroscopy study of heptahelicene layers on a Cu(111) substrate. Throughout the large accessible energy and angle range, no chirality induced spin asymmetry in photoemission could be observed. Possible reasons for the absence of signatures of the spin-dependent electron transmission through the chiral molecular layer are briefly discussed.

Impact of radiotherapy schedule on survival of patients treated with immune-checkpoint inhibitors for advanced melanoma and non-small cell lung cancer.

PURPOSE: Preclinical and clinical data suggest a potential benefit in the addition of radiotherapy (RT) to immune-checkpoint inhibitors (ICI) during the treatment of advanced cancers. Nevertheless, the ideal patients for this approach and the optimal RT regimen is still debated. MATERIAL AND METHODS: The aim of this study was to determine the effect RT schedule has on survival for advanced non-small cell lung cancer and melanoma patients (pts) treated with ICI (anti-PD1 or anti-CTLA4) and concomitant RT. RESULTS: A total of 58 pts were identified, of which 26 received RT concomitantly with ICI while the remaining 32 pts were treated with RT at the time of progression under ICI. The RT parameters associated with outcome include dose per fraction, biological effective dose, RT to all targets and lung irradiation. Independent predictors of improved progression-free survival were lung irradiation, melanoma histology, oligometastatic status (<6 metastasis), presence of liver metastasis, PNN<7000/mm3 and normal LDH. Independent predictors of improved overall survival were melanoma histology and normal LDH. Among pts who were irradiated at progression, 68.7% had an overall clinical benefit and had a median extension of ICI use by 2.3 months (range: 0-29.1), among which 2 presented with an abscopal effect. CONCLUSIONS: The irradiation of lung metastases may increase survival in patients under ICI. RT at progression could prolong the use of ICI, and neutrophilia and LDH should be considered during patient selection of this combined RT/ICI approach.

Nemolizumab efficacy in prurigo nodularis: onset of action on itch and sleep disturbances.

BACKGROUND: Patients with prurigo nodularis (PN) have multiple itchy nodules, impaired quality of life and sleep deprivation. Prurigo nodularis patients have a high burden of disease, primarily due to the intensity of the itch. It is reasonable to expect that rapid relief of itch - and associated improvement of sleep - are highly valued clinical outcomes for patients. Nemolizumab is an IL-31A-receptor inhibitor that modulates the neuroimmune response with reported positive efficacy and safety data in a phase 2 study of PN. OBJECTIVES: To evaluate the onset of action of nemolizumab on itch and sleep disturbances. METHODS: Post hoc analysis of a phase 2 trial of nemolizumab 0.5 mg/kg SC vs. placebo in patients (n = 70) with moderate-to-severe PN (≥20 nodules) and severe pruritus (NRS ≥ 7). Time to significant reduction was assessed for peak pruritus (PP) and sleep disturbance (SD) using numerical rating scales (NRS), also assessed was scratching time during sleep. RESULTS: Nemolizumab significantly reduced itch vs. placebo within 48 h (PP NRS -19.5% vs. -5.8%, respectively, P = 0.014). Significant difference between nemolizumab and placebo in reducing itch by ≥4 on PP NRS was achieved at Day 3 (23.5% vs. 0%, P < 0.001). A significant difference in SD NRS was reported by Day 4 (-24.0% vs. -4.3% placebo, P = 0.012). In addition, there was a separation between groups in SD responders (decrease of ≥4 points) in favour of nemolizumab by Day 2 (8.8% vs. 0%, P = 0.037). Sleep continued improving through Week 4, when there was a -56.0% reduction in SD NRS vs. -22.9% placebo (P < 0.001). Actigraphy data showed improvement in scratch/sleep duration for nemolizumab vs. placebo, respectively, by Week 1 (-32.15 vs. +28.15 min/h, P = 0.001). CONCLUSION: Nemolizumab has a rapid and robust onset of action in PN with itch reduction and improvement of sleep within 48 h.

Tildrakizumab efficacy and safety in patients with psoriasis and concomitant metabolic syndrome: post hoc analysis of 5-year data from reSURFACE 1 and reSURFACE 2.

BACKGROUND: Limited data are available on long-term efficacy and safety of biologics in patients with psoriasis and metabolic syndrome (MetS), a common comorbidity. OBJECTIVES: This analysis updates tildrakizumab efficacy and safety for up to 5 years in patients with and without MetS. METHODS: This was a post hoc analysis of the double-blind, randomized, placebo-controlled, phase 3 reSURFACE 1 (NCT01722331) and reSURFACE 2 (NCT01729754) trials in adult patients with moderate to severe chronic plaque psoriasis. Analyses included data through Week 244 from patients who continuously received tildrakizumab 100 (TIL100) or 200 mg (TIL200) and entered the extension studies, stratified by baseline MetS status. Efficacy was assessed via Psoriasis Area and Severity Index (PASI) scores. Safety was evaluated from exposure-adjusted incidence rates (EAIRs) of treatment-emergent adverse events (TEAEs). RESULTS: reSURFACE 1 and reSURFACE 2 analyses included 26 and 44 TIL100-treated patients with MetS, 98 and 167 TIL100-treated patients without MetS, 34 and 30 TIL200-treated patients with MetS, and 111 and 130 TIL200-treated patients without MetS, respectively. There were no clinically relevant differences in PASI 75/90/100 response rates at Week 244 between patients with vs without MetS. The proportion of patients with vs without MetS achieving absolute PASI score <3 at Week 244 was 53.8% vs 69.4% and 77.3% vs 80.8% in reSURFACE 1 and 2, respectively, for TIL100-treated patients and 58.8% vs 72.1% and 63.3% vs 72.3%, respectively, for TIL200-treated patients. In both studies, median reduction from baseline PASI score at all time points in patients with vs without MetS was >83% vs >89% for TIL100 and >85% vs >90% for TIL200. Pooled EAIRs of TEAEs, serious TEAEs, and TEAEs of special interest were similar in patients with and without MetS. CONCLUSIONS: Tildrakizumab maintains efficacy and a favorable safety profile over 5 years in patients with psoriasis regardless of MetS status.

Leg ulcers in childhood: A multicenter study in France.

BACKGROUND: Leg ulcers in adults are a major public health concern. Their incidence increases with age and many causes have been identified, predominantly associated with vascular diseases. Leg ulcers in children and teenagers are less frequent. The aim of our study was to identify the causes of leg ulcers in children and teenagers, and to evaluate their management. METHODS: This retrospective multicenter study was conducted by members of the Angio-dermatology Group of the French Society of Dermatology and of the French Society of Pediatric Dermatology. Data from children and teenagers (< 18 years), seen between 2008 and 2020 in 12 French hospitals for chronic leg ulcer (disease course>4 weeks), were included. RESULTS: We included 27 patients, aged from 2.3 to 17.0 years. The most frequent causes of leg ulcer were: general diseases (n=9: pyoderma gangrenosum, dermatomyositis, interferonopathy, sickle cell disease, prolidase deficiency, scleroderma, Ehlers-Danlos syndrome), vasculopathies (n=8: hemangioma, capillary malformation, arteriovenous malformation), trauma (n=4: bedsores, pressure ulcers under plaster cast), infectious diseases (n=4: pyoderma, tuberculosis, Buruli ulcer) and neuropathies (n=2). Comorbidities (59.3%) and chronic treatments (18.5%) identified as risk factors for delayed healing were frequent. The average time to healing was 9.1 months. DISCUSSION: Leg ulcers are less frequent in children and teenagers than in adults and their causes differ from those in adults. Comorbidities associated with delayed healing must be identified and managed. Children and teenagers tend to heal faster than adults, but a multidisciplinary management approach is necessary.

Secukinumab efficacy in reducing the severity and the psychosocial impact of moderate-to-severe psoriasis as assessed by the Simplified Psoriasis Index: results from the IPSI-PSO study.

BACKGROUND: The utility of the Simplified Psoriasis Index (SPI), a recently developed multidomain tool for assessing psoriasis, was investigated in a study assessing response to secukinumab. METHODS: In an open-label, multicentre study involving 17 French centres, patients with moderate-to-severe plaque psoriasis received secukinumab 300 mg subcutaneously once weekly from baseline to W4, then every 4 weeks until W48. Dermatologist-scored SPI psoriasis severity (proSPI-s) was compared with Psoriasis Area and Severity Index (PASI). Patient self-assessed severity (saSPI-s) and psychosocial impact (SPI-p) were compared with PASI and Dermatology Life Quality Index (DLQI), respectively. RESULTS: We included 120 patients (69.2% male; mean age 45.9 years; mean duration of psoriasis 21.6 years). Mean baseline scores were as follows: proSPI-s 24.9, saSPI-s 23.5, PASI 23.1, SPI-p 8.2 and DLQI 13.6. Severity scores achieved by 16 weeks (proSPI-s 2.3, saSPI-s 2.2 and PASI 2.2) were maintained to W52. Reductions in mean psychosocial impact scores were maintained to W52 (SPI-p and DLQI, respectively, 2.1 and 1.5 at W16; 1.5 and 1.9 at W52). CONCLUSIONS: Decrease of PASI scores in response to secukinumab was closely correlated with proSPI-s, supporting the latter's suitability for assessing response to therapy. Although the correlation between PASI and saSPI-s was slightly weaker, patients were able to complete a valid assessment of their psoriasis independently, and thus potentially remotely. With the added benefit of psychosocial impact assessment (SPI-p), SPI provides a valid tool enabling patients to assess their own psoriasis, remotely if necessary.

Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2).

BACKGROUND: Tralokinumab, a fully human monoclonal antibody, specifically neutralizes interleukin-13, a key cytokine driving peripheral inflammation in atopic dermatitis (AD). In phase II studies, tralokinumab combined with topical corticosteroids provided early and sustained improvements in AD signs and symptoms. OBJECTIVES: To evaluate the efficacy and safety of tralokinumab monotherapy in adults with moderate-to-severe AD who had an inadequate response to topical treatments. METHODS: In two 52-week, randomized, double-blind, placebo-controlled, phase III trials, ECZTRA 1 and ECZTRA 2, adults with moderate-to-severe AD were randomized (3 : 1) to subcutaneous tralokinumab 300 mg every 2 weeks (Q2W) or placebo. Primary endpoints were Investigator's Global Assessment (IGA) score of 0 or 1 at week 16 and ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16. Patients achieving an IGA score of 0 or 1 and/or EASI 75 with tralokinumab at week 16 were rerandomized to tralokinumab Q2W or every 4 weeks or placebo, for 36 weeks. The trials were registered with ClinicalTrials.gov: NCT03131648 and NCT03160885. RESULTS: At week 16, more patients who received tralokinumab vs. placebo achieved an IGA score of 0 or 1: 15·8% vs. 7·1% in ECZTRA 1 [difference 8·6%, 95% confidence interval (CI) 4·1-13·1; P = 0·002] and 22·2% vs. 10·9% in ECZTRA 2 (11·1%, 95% CI 5·8-16·4; P < 0·001) and EASI 75: 25·0% vs. 12·7% (12·1%, 95% CI 6·5-17·7; P < 0·001) and 33·2% vs. 11·4% (21·6%, 95% CI 15·8-27·3; P < 0·001). Early improvements in pruritus, sleep interference, Dermatology Life Quality Index, SCORing Atopic Dermatitis and Patient-Oriented Eczema Measure were observed from the first postbaseline measurements. The majority of week 16 tralokinumab responders maintained response at week 52 with continued tralokinumab treatment without any rescue medication (including topical corticosteroids). Adverse events were reported in 76·4% and 61·5% of patients receiving tralokinumab in ECZTRA 1 and ECZTRA 2, respectively, and in 77·0% and 66·0% of patients receiving placebo in ECZTRA 1 and ECZTRA 2, respectively, in the 16-week initial period. CONCLUSIONS: Tralokinumab monotherapy was superior to placebo at 16 weeks of treatment and was well tolerated up to 52 weeks of treatment.