Role of Sleep Apnea and Long-Term CPAP Treatment in the Prognosis of Patients With Melanoma: A Prospective Multicenter Study of 443 Patients.

BACKGROUND: OSA has been associated with increased incidence and aggressiveness of melanoma. However, the long-term impact of OSA and CPAP treatment on the prognosis of melanoma remains unexplored. RESEARCH QUESTION: Are OSA and CPAP treatment associated independently with a poor prognosis for cutaneous melanoma? STUDY DESIGN AND METHODS: Four hundred forty-three patients with a diagnosis of cutaneous melanoma (2012-2015) underwent a sleep study within 6 months of diagnosis. The main 5-year outcome of the study was a composite of melanoma recurrence, metastasis, or mortality. Patients were divided into four groups: baseline apnea-hypopnea index (AHI) of fewer than 10 events/h (no OSA; control group), OSA treated with CPAP and good adherence, untreated or poor CPAP adherence in moderate (AHI, 10-29 events/h), and severe OSA (AHI, ≥ 30 events/h). Survival analysis was used to determine the independent role of OSA and CPAP treatment on melanoma composite outcome. RESULTS: Three hundred ninety-one patients (88.2%) were available for analysis at 5-year follow-up (mean age, 65.1 ± 15.2 years; 49% male; Breslow index, 1.7 ± 2.5 mm). One hundred thirty-nine patients had AHI of fewer than 10 events/h (control group); 78 patients with OSA were adherent to CPAP; and 124 and 50 patients had moderate and severe OSA, respectively, without CPAP treatment. Median follow-up was 60 months (interquartile range, 51-74 months). During follow-up, 32 relapses, 53 metastases, and 52 deaths occurred (116 patients showed at least one of the main composite outcomes). After adjusting for age, sex, sentinel lymph nodes affected at diagnosis, BMI, diabetes, nighttime with an oxygen saturation below 90%, Breslow index, Epworth sleepiness scale scores, and melanoma treatment, moderate (hazard ratio [HR], 2.45; 95% CI, 1.09-5.49) and severe OSA (HR, 2.96; 95% CI, 1.36-6.42) were associated with poorer prognosis of melanoma compared with the control group. However, good adherence to CPAP avoided this excess risk (HR, 1.66; 95% CI, 0.71-3.90). INTERPRETATION: Moderate to severe untreated OSA is an independent risk factor for poor prognosis of melanoma. Treatment with CPAP is associated with improved melanoma outcomes compared with untreated moderate to severe OSA.

Brentuximab vedotin in the treatment of cutaneous T-cell lymphomas: Data from the Spanish Primary Cutaneous Lymphoma Registry.

BACKGROUND: Brentuximab vedotin (BV) has been approved for CD30-expressing cutaneous T-cell lymphoma (CTCL) after at least one previous systemic treatment. However, real clinical practice is still limited. OBJECTIVES: To evaluate the response and tolerance of BV in a cohort of patients with CTCL. METHODS: We analysed CTCL patients treated with BV from the Spanish Primary Cutaneous Lymphoma Registry (RELCP). RESULTS: Sixty-seven patients were included. There were 26 females and the mean age at diagnosis was 59 years. Forty-eight were mycosis fungoides (MF), 7 Sézary syndrome (SS) and 12 CD30+ lymphoproliferative disorders (CD30 LPD). Mean follow-up was 18 months. Thirty patients (45%) showed at least 10% of CD30+ cells among the total lymphocytic infiltrate. The median number of BV infusions received was 7. The overall response rate (ORR) was 67% (63% in MF, 71% in SS and 84% in CD30 LPD). Ten of 14 patients with folliculotropic MF (FMF) achieved complete or partial response (ORR 71%). The median time to response was 2.8 months. During follow-up, 36 cases (54%) experienced cutaneous relapse or progression. The median progression free survival (PFS) was 10.3 months. The most frequent adverse event was peripheral neuropathy (PN) (57%), in most patients (85%), grades 1 or 2. CONCLUSIONS: These results confirm the efficacy and safety of BV in patients with advanced-stage MF, and CD30 LPD. In addition, patients with FMF and SS also showed a favourable response. Our data suggest that BV retreatment is effective in a proportion of cases.

Effectiveness, survival and safety of guselkumab attending to basal characteristics in moderate-to-severe psoriatic patients: a cohort study.

Background: Psoriasis is a chronic inflammatory disease which can impact quality of life. In the past decade multiple biologic treatments have been released with encouraging results. Guselkumab is a monoclonal antibody targeting IL-23p19. Multiple randomized clinical trials have demonstrated its efficacy in psoriasis, but response differences among patient subpopulations have not been extensively reported. Furthermore, patients in real life are often non-eligible for clinical trials and their responses may differ from pivotal studies. Methods: This is a retrospective, observational study of real clinical practice of patients receiving guselkumab treatment in Spain. Patients treated with guselkumab were included between February 2019 to December 2021. This study evaluates the potential differential effect of baseline demographic and disease characteristics on therapeutic responses to guselkumab. We measured effectiveness and survival by the psoriasis area and severity index, the dermatology life quality index as well as Kaplan meier curves, respectively. Categorical and quantitative variables are reported with frequencies, and with mean and standard deviation, respectively. Differences between groups in psoriasis area and severity index and dermatology life quality index, were calculated using a mixed-effects analysis. Survival was calculated using Kaplan meier curves and log-rank tests. Results: A total of 87 patients were included. In this study, our objective was to evaluate the effectiveness, safety and survival of guselkumab attending to demographic characteristics. No differences in psoriasis area and severity index or dermatology life quality index baseline values or therapeutic responses were noted at 52 weeks of follow-up among all the subgroups analysed (age, sex, psoriasis duration, body mass index, and comorbidities). A difference in drug survival was only seen between gender groups. Conclusions: Our research has demonstrated the consistency of guselkumab effectiveness across patient subgroups. No baseline features affected the effectiveness or drug survival of guselkumab, except for lower drug survival in female patients.

Risankizumab: Efficacy, Safety, and Survival in the Mid-Term (52 Weeks) in Real Clinical Practice in Andalusia, Spain, According to the Therapeutic Goals of the Spanish Psoriatic Guidelines.

Introduction. Risankizumab is a humanized monoclonal antibody of the immunoglobulin G1 (IgG1) type that binds selectively, and with high affinity, to the p19 subunit of interleukin-23 (IL-23), resulting in the inhibition of inflammation and clinical symptoms associated with psoriasis. Its introduction has managed to increase the levels of efficacy and safety (improving upon those previously presented by the anti-IL-23 class). Material and methods. Retrospective analysis of a multicenter, observational study of real clinical practice, including patients with moderate-to-severe plaque psoriasis in treatment with risankizumab. This cross-sectional analysis includes information on patients from May 2020 to June 2022. A total of six tertiary hospitals in Andalusia (Spain) participated in this study. Analyses were performed "as observed" using GraphPad Prism version 8.3.0 for Windows. Results. Regarding the percentage of patients who reached PASI 90 or PASI 100 at week 52, 92.5% achieved the therapeutic goal of PASI 90, and 78.5% reached PASI 100. When analyzing the results by absolute PASI, we found that 78.5% (n = 33) obtained PASI 0, 85.7% (n = 36) obtained PASI ≤ 1, and all patients achieved PASI ≤ 3 (disease control). Discussion. Risankizumab has shown promising results in the control of psoriasis in the long-term, with a high percentage of patients (>80%) maintaining PASI 90 and PASI 100 up to 52 weeks of treatment. No abnormal safety findings have been reported, and risankizumab appears to be a solid treatment in the different scenarios analyzed.

Guselkumab dosing interval optimization in adult patients with moderate-to-severe psoriasis switching from ustekinumab.

Psoriasis (PSO) is an inflammatory disease that emerges as a dysregulation of the interleukin 23 (IL23)/Th17 axis. There are many biologic alternatives to treat PSO that are administered monthly, every 2 months and every 3 months. Guselkumab (GUS) is a fully human monoclonal antibody, that selectively blocks IL-23 through binding to its p19 subunit. There is scarce evidence on dose optimization of GUS in psoriatic patients. Retrospective, observational case series review which includes patients with moderate-to-severe PSO who switched from ustekinumab to GUS as standard dosing or every 12 weeks, regarding daily clinical practice of every dermatology unit. Clinical and demographic data from patients were included from February 2019 to October 2021. Analyses were performed "as observed" using GraphPad Prism version 8.3.0 for Windows (GraphPad Software, San Diego, CA, USA, www.graphpad.com). A total of 30 patients were included in this study: 20 receiving GUS as standard of care (SC) and 10 receiving an optimized dosing (Q12W) (GUS every 12 weeks without induction). The Q12W group presented greater percentage of comorbidities and was less refractory to previous biologic treatments. After receiving GUS as SC or Q12W, psoriasis area severity index and dermatology life quality index improved dramatically in both groups up to 52 weeks. Survival was 87.2% and 100% for the SC and Q12W, respectively, and there were not safety signals. Our case series of 10 patients receiving GUS every 12 weeks without induction showed a good effectiveness and safety profile accompanied by an excellent treatment survival. However, more studies are needed to provide strong evidence of dosing alternatives different than SC.

Super-Responders in Moderate-Severe Psoriasis under Guselkumab Treatment: Myths, Realities and Future Perspectives.

A fast skin clearance is the main goal to achieve in psoriasis treatment. Patients that present a fast and exceptional improvement with treatment are called super-responders (SR). There is no consensus on the definition of SR with respect to psoriasis. Included herein is a retrospective analysis of a multicenter, observational study of real clinical practices including patients with moderate-to-severe plaque PSO undergoing treatment with Guselkumab (GUS). This cross-sectional analysis includes information on patients between February 2019 to February 2022. A SR is a patient that achieved a PASI = 0 at weeks 12 and 24. Analyses have been performed "as observed" using GraphPad Prism version 8.3.0 for Windows (GraphPad Software, San Diego, CA, USA, At baseline, the PASI is significantly correlated with VAS_pruritus, BSA, and DLQI, while DLQI is significantly correlated with VAS_pruritus. Significant correlations increase in number and magnitude over the follow-up time. In relation to the univariate logistic models carried out, only three variables showed a significant association with the super-responder variable: depression, VAS_pruritus, and DLQI.SR patients, who show a faster evolution in PASI and BSA improvement than non-SRs. Based on the results obtained, it would be possible to also include DLQI and VAS_pruritus in the broader concept of the SR.

Guselkumab as a switching strategy after anti-TNFα, anti-IL17, or anti-IL12/23 therapies in moderate-to-severe psoriasis.

The IL23/Th17 axis plays a strategic role in psoriasis (PSO). Guselkumab (GUS) is a selective inhibitor of the IL23p19 subunit. Its introduction has managed to increase the levels of efficacy, safety and survival in PSO. In real clinical practice, patients can loss effectiveness or suffered adverse events that forces a change in their treatments. There is scarce evidence of the effectiveness, safety, and survival of GUS in real clinical practice after anti-TNFα, anti-IL17, and/or anti-IL12/23. This is multicenter, observational and retrospective study of real clinical practice includes patients with moderate-to-severe plaque PSO in treatment with GUS. The objective of the study was to evaluate the effectiveness of GUS after anti-TNFα, anti-IL17, and anti-IL12/23. The study includes clinical information from February 2019 to February 2022. PASI, BSA, Pruritus, DLQI, survival, and safety were evaluated up to 76 weeks. Analyses were performed "as observed" using GraphPad Prism version 8.3.0 for Windows. A total of 103 patients were included in the analysis. At baseline there were significant differences between the anti-TNF, anti-IL17, and anti-IL12/23 groups for (1) dyslipidemia; (2) number of previous biological treatments and (3) PASI, BSA, VAS Pruritus, and DLQI scores. The effectiveness of GUS in terms of PASI, BSA, Pruritus, and DLQI was not impacted by previous biological alternatives. Treatment survival including discontinuations due to lack of effectiveness or safety reasons was 100%, 92.7%, and 92.1% for anti-TNFα, anti-IL17, and anti-IL12/23, respectively, at 130 weeks. No differences were found between groups. One adverse event was reported in the anti-LI12/23 group. The mid-term effectiveness, safety and survival of GUS if not impacted by previous biological therapy as anti-TNFα, anti-IL17, and/or anti-IL12/23. Our results indicate that GUS could be a switching strategy in patients who fail or present AE to other biological alternatives in moderate-to-severe PSO.

Super responders to guselkumab treatment in moderate-to-severe psoriasis: a real clinical practice pilot series.

BACKGROUND: The term super responders defines a subset of patients with moderate-to-severe psoriasis that present a rapid and higher rate of response to biological treatments in comparison to the general population. Little scientific evidence to explain the behavior and clinical characteristics of these psoriatic patients has been published thus far. Its characterization could be important to improve therapeutic optimization and to identify the profile of patients that will respond efficiently to biological treatments. OBJECTIVES: The main objective of this study was to evaluate and characterize the proportion of super-responder patients (who achieved PASI = 0 at week 12 and 24) in a total of 87 patients with moderate-to-severe psoriasis treated with guselkumab. Also, our intent was to analyze and evaluate differences in response to guselkumab in absolute PASI, PASI 75, PASI 90, PASI 100, BSA, VAS pruritus, and DLQI between groups. RESULTS: A total of 14 out of 87 patients treated with guselkumab were characterized as SR. No differences in demographic characteristics were found. The percentage of patients reaching PASI 75, PASI 90, and PASI 100 were numerically greater for SR than N-SR at week 12, 24, 36, and 52. These differences were more pronounced for PASI 100 > PASI 90 > PASI 75. SR performed better and faster to guselkumab treatment as assessed by absolute PASI, BSA, VAS pruritus, and DLQI. Statistically significant differences were found in absolute PASI, BSA, VAS pruritus, and DLQI between groups along the 52 weeks of study. No differences in drug survival were found between groups (P = 0.3326). CONCLUSION: Our study demonstrated for the first time, in a real clinical practice setting, the presence of a subpopulation of patients that super respond to guselkumab at week 12 and 24 and maintain this efficacy for 52 weeks. Further research must be performed to identify basal specific characteristics of this SR population.

Guselkumab: Mid-term effectiveness, drug survival, and safety in real clinical practice.

Guselkumab is a fully human immunoglobulin-G1-lambda (IgG1λ) monoclonal antibody that binds selectively to the p19 subunit of interleukin 23. Few series of real clinical practice that reflect the use of guselkumab have been published so far, including the measure of survival at more than 52 weeks. An observational, longitudinal, retrospective study of real clinical practice of patients with moderate to severe psoriasis receiving treatment with guselkumab 100 mg subcutaneous every 8 weeks in five tertiary hospitals in Andalusia (Spain) was carried out. A total of 87 patients were included in this study. Disease severity and treatment response was assessed by PASI, BSA, VAS pruritus, and DLQI at baseline and after 4, 12, 24, 36, 52, and 76 weeks. Data are presented as mean ± SD for continuous variables, and number and percentage for categorical variables. To determine the differences between visits in PASI, BSA, VAS pruritus, and DLQI a Wilcoxon matched-pairs test was performed. The survival of guselkumab was calculated using Kaplan-Meier survival analysis. Our population presented with a mean age of 49.9 years, 60.9% of them were male, had a mean PSO evolution of 20.4 (9.5) years. A total of 79.3% were obese or presented with overweight and had several comorbidities (dyslipidemia 28.7%, arterial hypertension 23% and 20% diabetes among others). At baseline their disease parameters were: PASI = 14.6 (7.2), BSA = 22.3 (16.6), VAS pruritus = 6.0 (2), and DLQI = 15.8 (5). After 52 weeks their disease improved to PASI = 0.9 (1.1), BSA = 1.0 (1.8), VAS pruritus = 0.47 (0.88), and DLQI = 1.54 (2.50). The percentage of patients who achieved PASI 75, 90, and 100 at 52 weeks was 90.3%, 71%, and 51.6%, respectively. The patients evaluated at week 76 (n = 3) reached PASI 0, BSA 0, and DLQI 0. After 93.4 weeks (1 year, 9 months, and 14 days), the overall survival rate was 94% (4 events were reported). A total of four patients discontinue to AE or lack of efficacy after 76 weeks. Guselkumab showed excellent results in the control of psoriasis in the mid-term with an elevated number of patients maintaining treatment after 52 to 76 weeks and a good safety profile.

Efficacy of an Innovative Film-Forming Wound Dressing on Open Wounds.

Standards in post-surgery wound care management require a rapid healing process in order to prevent and minimize abnormal scarring. For the healing process to start as early as possible, the ideal dressing should be applied directly on the open wound and perfectly adapt to it. The authors report a case study series regarding the efficacy of a flexible film-forming wound dressing in the form of a gel (Stratamed®, Stratpharma AG, Switzerland) that is approved for the use on open wounds and injured skin. Evidence from the current study shows that, while remaining safe to use, the dressing was efficacious in promoting epithelialization and accelerated wound healing of areas in which skin integrity had been compromised, and at the same time prevented the formation of abnormal scars. Results were observed across a broad range of dermatologic surgical procedures. All treated conditions showed a beneficial outcome, as well as an overall favorable patient treatment perception.

Sleep-Disordered Breathing Is Independently Associated With Increased Aggressiveness of Cutaneous Melanoma: A Multicenter Observational Study in 443 Patients.

BACKGROUND: Sleep-disordered breathing (SDB) has been associated with a greater incidence and mortality of cancer, although such findings are inconsistent. However, no large studies are currently available to investigate this association in patients with a specific type of cancer. This study seeks to assess potential relationships between SDB severity and aggressiveness markers of cutaneous melanoma. METHODS: Four hundred and forty-three patients with a diagnosis of melanoma underwent a sleep study within 6 months of diagnosis. General demographics were collected, along with melanoma characteristics and polygraphic parameters consisting of the apnea-hypopnea index (AHI) and indices of both continuous and intermittent night-time oxyhemoglobin desaturation (DI4%). An exploration of independent relationships between SDB and various objective melanoma aggressiveness markers (Breslow index, presence of ulceration, presence of regression, mitotic index, stage of severity, damage to the sentinel lymph, and spreading of the melanoma) was performed. RESULTS: Patients in the upper tertiles of AHI or DI4% were 1.94 (95% CI, 1.14-3.32; P = .022) and 1.93 (95% CI, 1.14-3.26; P = .013) times more likely, respectively, to present with aggressive melanoma (Breslow index > 1 mm) than those in the lowest tertiles of these sleep attributes after adjustment for age, sex, tumor location, and BMI. This association was particularly prominent among patients < 56 years of age with Breslow index > 2 mm. The presence of the additional markers of aggressiveness was also associated with higher AHI and DI4% values. CONCLUSIONS: The severity of SDB was independently associated with greater aggressiveness of cutaneous melanoma, particularly among younger patients.

Interstitial Granulomatous Dermatitis due to a Rare Myeloproliferative Neoplasia.

Interstitial granulomatous dermatitis (IGD) was first described in 1993 by Ackerman as a cutaneous reactive disease in patients with arthritis. Since then, numerous cases associated with different hematological and rheumatic disorders have been reported. IGD is a polymorphic entity that usually involves the upper part of the trunk. Histologically, it is defined as a diffuse dermal histiocytic infiltrate of different densities surrounded by fragmented collagen. We report the case of a 56-year-old man with pruritic papules affecting neck, proximal arms and thorax associated with weight loss and chronic fatigue for six months. Two punch biopsies were taken and the specimens showed lymphohistiocytic interstitial infiltrates with fragmented collagen and elastic fibers in dermis. IGD was diagnosed as first manifestation of a rare chronic myeloproliferative hematologic disorder (cMPD) with rearrangement of beta-receptor for platelet-derived growth factor (PDGFRB). After two months of imatinib, lesions regressed completely.

Intermittent Hypoxia Is Associated With High Hypoxia Inducible Factor-1α but Not High Vascular Endothelial Growth Factor Cell Expression in Tumors of Cutaneous Melanoma Patients.

Epidemiological associations linking between obstructive sleep apnea and poorer solid malignant tumor outcomes have recently emerged. Putative pathways proposed to explain that these associations have included enhanced hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) cell expression in the tumor and altered immune functions via intermittent hypoxia (IH). Here, we examined relationships between HIF-1α and VEGF expression and nocturnal IH in cutaneous melanoma (CM) tumor samples. Prospectively recruited patients with CM tumor samples were included and underwent overnight polygraphy. General clinical features, apnea-hypopnea index (AHI), desaturation index (DI4%), and CM characteristics were recorded. Histochemical assessments of VEGF and HIF-1α were performed, and the percentage of positive cells (0, <25, 25-50, 51-75, >75%) was blindly tabulated for VEGF expression, and as 0, 0-5.9, 6.0-10.0, >10.0% for HIF-1α expression, respectively. Cases with HIF-1α expression >6% (high expression) were compared with those <6%, and VEGF expression >75% of cells was compared with those with <75%. 376 patients were included. High expression of VEGF and HIF-1α were seen in 88.8 and 4.2% of samples, respectively. High expression of VEGF was only associated with increasing age. However, high expression of HIF-1α was significantly associated with age, Breslow index, AHI, and DI4%. Logistic regression showed that DI4% [OR 1.03 (95% CI: 1.01-1.06)] and Breslow index [OR 1.28 (95% CI: 1.18-1.46)], but not AHI, remained independently associated with the presence of high HIF-1α expression. Thus, IH emerges as an independent risk factor for higher HIF-1α expression in CM tumors and is inferentially linked to worse clinical CM prognostic indicators.

A prospective multicenter cohort study of cutaneous melanoma: clinical staging and potential associations with HIF-1α and VEGF expressions.

Melanoma is a highly prevalent cancer that is associated with substantial mortality. Although clinical staging procedures can serve as relatively robust prognostic indicators, we aimed to determine whether assessments of the abundance of hypoxia inducible factor-1α (HIF-1α) or vascular endothelial growth factor (VEGF) in postexcisional melanoma tumor tissues may enable more accurate determination of tumor aggressiveness. We carried out a multicenter prospective study, in which we systematically evaluated 376 consecutive patients diagnosed with melanoma, and performed histochemical assessments for both HIF-1α and VEGF immunoreactivity in the tumor biopsies. Multivariate analyses showed that higher HIF-1α expression, but not high VEGF, were associated significantly and independently with increased tumor aggressiveness as derived from several well-established aggressiveness criteria. A limitation of this study was that this was a descriptive prospective study lacking a post-hoc verification arm. Thus, the presence of increased numbers of positively labeled HIF-1α cells in melanoma tumors may potentially serve as an indicator of tumor phenotype and prognosis, and accordingly guide therapy.

Association between sleep disordered breathing and aggressiveness markers of malignant cutaneous melanoma.

Some recent studies have shown an association between sleep disordered breathing (SDB) and cancer mortality and incidence but no study has focused on a specific type of cancer. The objective of this study was to analyse the relationship between the severity of SDB and factors related to cutaneous malignant melanoma (CMM) aggressiveness. We performed a multicentre observational study in 82 consecutive patients diagnosed with CMM. 56 patients in whom melanoma measurements were available were finally included in the study. Melanoma measurements of aggressiveness included: tumour mitotic rate, Breslow index, presence of ulceration, stage of disease and growth rate of melanoma. A sleep study was performed in all the included patients. Multivariate analyses were used to examine the independent relationship between SDB severity (apnoea-hypopnea index (AHI) and nocturnal oxygen desaturation indexes (ODI3% and ODI4%)) and measures of CMM aggressiveness. 60.7% of patients had SDB (AHI ≥ 5) and 14.3% severe obstructive sleep apnoea (AHI ≥ 30). In fully adjusted multivariate analyses, AHI (OR 1.08, 95% CI 1.02-1.14), ODI3% (OR 1.08, 95% CI 1.02-1.11) and ODI4% (OR 1.1, 95% CI 1.02-1.2) were independently associated with an increased melanoma growth rate. Furthermore, AHI, ODI4% and ODI3% were significantly correlated with other aggressiveness factors of CMM, such as Breslow index, presence of ulceration and mitotic index. SDB severity markers are associated with some aggressiveness markers of CMM.