Expert consensus on the persistence of biological treatments in moderate-to-severe psoriasis.

BACKGROUND: Treatment persistence is becoming a useful measure to evaluate long-term effectiveness and safety of biological therapies in real-world settings. OBJECTIVE: The main objective of this study was to explore the scientific opinion of a panel of dermatologists and hospital pharmacists to reach a consensus about the impact, causes, and best strategies and interventions that might be associated with improved drug persistence in patients with psoriasis in Spain. METHODS: This research was conducted using a modified Delphi method organized in two rounds and involving a panel of 90 dermatologists and 34 hospital pharmacists. A questionnaire of 70 items was developed. The items proposed to reach a consensus included topics such as definitions and measures in the treatment of psoriasis, analysis of treatment persistence, factors that may influence treatment persistence, impact of treatment persistence and economic cost of treatment. RESULTS: Dermatologists reached a consensus on 77.1% of the items proposed, and hospital pharmacists reached a consensus on 71.4%. Both groups agreed that it is important to use standardized measures in the evaluation of treatment maintenance over time. Dermatologists agreed that treatment survival, persistence and retention are synonymous, but hospital pharmacists considered only treatment persistence as a valid term. In addition, panelists agreed that drug persistence is an indicator of success in the treatment of psoriasis that may be influenced by a drug's effectiveness and safety profile, as well as by patient satisfaction. They agreed that the different causes of treatment discontinuation should be considered in Kaplan-Meier analysis of treatment persistence. Moreover, treatment persistence was agreed to decrease the cost of therapy. CONCLUSION: This Delphi consensus highlights the different perspectives of dermatologists and hospital pharmacists regarding the interpretation of treatment persistence, and the challenge of harmonizing the results obtained.

Tumor regrowth and development of keratinocytic neoplasms in patients under smoothened inhibition: in vivo assessment with reflectance confocal microscopy.

BACKGROUND: The regrowth of a tumor after complete clinical response and the development of keratinocytic neoplasms while patients are still undergoing continuous vismodegib have stressed the importance of the accurate monitoring to detect recurrences earlier and ensure the best possible outcome. OBJECTIVE: The objective of this study was to determine the role of reflectance confocal microscopy (RCM) in monitoring the response of locally advanced basal cell carcinoma (laBCC) to vismodegib and to discard secondary resistance. METHODS: Seven patients presenting with nine laBCC, were prospectively included and their response to this drug was assessed by means of clinical examination, dermoscopy, and RCM. The study was conducted at the Melanoma Unit in Hospital Clinic of Barcelona, between June 2012 and March 2013. RESULTS: Histologically confirmed lesion 10 mm or larger in diameter for which surgery was contraindicated and radiation therapy was inappropriate. The median patient age was 73 years and the most common histological type was infiltrating BCC. RCM allowed the identification of residual tumor in two lesions and to confirm complete response in the other four cases. Two patients developed new lesions within the tumor bed, they were assessed by RCM showing features of actinic keratosis which were confirmed by histopathology. CONCLUSION: The use of in vivo RCM allowed the characterization of the dynamic morphologic changes in tumor response helping to better define partial response and to differentiate it from secondary resistance. Another interesting observation was the recognition of a phenomenon characterized by the development of keratinocytic neoplasms within the tumor bed.

Spanish version of the Actinic Keratosis Quality of Life questionnaire.

BACKGROUND: Patient-reported outcome measures are very important outcomes. For specific diseases, health-related quality of life-instruments (HRQoL) are increasingly used to provide data on patients' overall perceptions of the course of a given disease. Actinic keratoses (AKs) are common keratotic lesions that occur on chronically sunlight-exposed skin. Only few studies regarding HRQoL in AKs have been made. OBJECTIVE: In order to be able to compare HRQoL among different countries and cultures, we aimed to translate and validate the Actinic Keratosis Quality of Life (AKQoL) questionnaire into Spanish and quantify the impairment caused by AKs in Spanish patients. METHODS: The AKQoL was translated. Then, 15 patients with AKs were interviewed to ensure cultural adaption before it was tested in one hundred patients with AK lesions at the Melanoma Unit of Hospital Clinic in Barcelona. RESULTS: Validation showed high interitem correlations, as well as a high correlation of each item and the total score. Internal consistency (Cronbach's coefficient alpha) was also high at 0.91 and an alpha value of 0.90 at retest. The test-retest correlation was 0.96, and the intraclass coefficient was 0.98. CONCLUSION: The presented data support the AKQoL Spanish version as a valid and reliable HRQoL questionnaire for the description of AK-related QoL and may provide a method for comparison of AK specific QoL between different cultures and countries.

Closed-loop gastric electrical stimulation versus laparoscopic adjustable gastric band for the treatment of obesity: a randomized 12-month multicenter study.

OBJECTIVE: To compare the weight loss, change in quality of life (QOL) and safety of closed-loop gastric electrical stimulation (CLGES) versus adjustable gastric band (LAGB) in the treatment of obesity. METHODS: This multicenter, randomized, non-inferiority trial randomly assigned the patients in a 2:1 ratio to laparoscopic CLGES versus LAGB and followed them for 1 year. We enrolled 210 patients, of whom 50 were withdrawn preoperatively. Among 160 remaining patients (mean age=39±11 years; 75% women; mean body mass index=43±6 kg m-2) 106 received CLGES and 54 received LAGB. The first primary end point was non-inferiority of CLGES versus LAGB, ascertained by the proportion of patients who, at 1 year, fulfilled: (a) a ⩾20% excess weight loss (EWL); (b) no major device- or procedure-related adverse event (AE); and (c) no major, adverse change in QOL. Furthermore, ⩾50% of patients had to reach ⩾25% EWL. The incidence and seriousness of all AE were analyzed and compared using Mann-Whitney's U-test. RESULTS: At 1 year, the proportions of patients who reached all components of the primary study end point were 66.7 and 73.0% for the LAGB and CLGES group, respectively, with a difference of -6.3% and an upper 95% CI of 7.2%, less than the predetermined 10% margin for confirming the non-inferiority of CLGES. The second primary end point was also met, as 61.3% of patients in the CLGES group reached ⩾25% EWL (lower 95% CI=52.0%; P<0.01). QOL improved significantly and similarly in both groups. AE were significantly fewer and less severe in the CLGES than in the LAGB group (P<0.001). CONCLUSIONS AND RELEVANCE: This randomized study confirmed the non-inferiority of CLGES compared with LAGB based on the predetermined composite end point. CLGES was associated with significantly fewer major AE.

Treatment monitoring of 0.5% 5-fluorouracil and 10% salicylic acid in clinical and subclinical actinic keratoses with the combination of optical coherence tomography and reflectance confocal microscopy.

BACKGROUND: Reflectance confocal microscopy (RCM) and high-definition optical coherence tomography (HD-OCT) allow the observation in vivo of dynamic changes in response to non-surgical treatment of actinic keratosis and field of cancerisation. OBJECTIVE: To non-invasively assess the pharmacodynamic changes induced by treatment with low dose 5-fluorouracil and 10% salicylic acid by means of RCM and high-definition OCT in field cancerization and actinic keratosis. METHODS: Twenty patients aged >50 years with diagnosis of actinic keratosis on the head and face and indication for treatment with 0.5% 5-fluorouracil and 10% salicylic acid were enrolled. An area of 25 cm² including visible type I and II AK and subclinical AK was treated once daily during 6 weeks and examination was performed with RCM and HD-OCT before treatment and 2 weeks after the end of treatment RESULTS: High-definition optical coherence tomography results at baseline of mean thickness of the stratum corneum and epidermis were in AK 10.4 (SD = 4.99) and 43.3 (SD = 24.01) µm respectively and in subclinical AK 3.7 (SD = 2.15) and 30.05 (SD = 16.85) µm. At week 8 (2 weeks after the end of treatment) measurements of stratum corneum and epidermis were significantly reduced in AK and subclinical AK for stratum corneum and epidermis. In RCM at week 8 scaling, detached corneocytes, atypical honeycomb, round nucleated cells in the spinosum granulosum layer, round vessels (dermal papillae), inflammatory cells and total AK score were significantly reduced in AK and subclinical AK. CONCLUSIONS: Evaluation of AK and subclinical AK by RCM and HD-OCT showed objective improvement after treatment with 5-fluorouracil and 10% salicylic acid. These methods allowed the study of dynamic changes in the tissue at a subclinical level.

High-definition optical coherence tomography algorithm for the discrimination of actinic keratosis from normal skin and from squamous cell carcinoma.

BACKGROUND: Preliminary studies described morphological features of actinic keratosis (AK) and squamous cell carcinoma (SCC) imaged by High-Definition Optical Coherence Tomography (HD-OCT) and suggested that this technique may aid in their diagnosis. However, systematic studies evaluating the accuracy of HD-OCT for the diagnosis of AK and SCC are lacking so far. OBJECTIVE: In this study, we sought to design an algorithm for AK classification that could (i) distinguish SCC from AK and normal skin, (ii) differentiate AK from normal skin and (iii) discriminate AKs with adnexal involvement from those without. METHODS: A total of 53 histopathologically confirmed lesions (37 AKs and 16 SCC) were imaged by HD-OCT. Fifty-three HD-OCT images of normal skin of healthy volunteers, with matched age, skin type and anatomic site, were taken as reference. By comparing these 106 en face and cross-sectional HD-OCT images, particular features were selected based on their potential to discriminate AK from normal skin and from SCC, and to assess adnexal involvement in AK. This study represents a training set not a testing set. Severe (>300 µm) hyperkeratotic AKs were not included in this study. RESULTS: Particular features with high Phi coefficient could be identified. The absence of an outlined dermo-epidermal junction (DEJ) on cross-sectional images allowed discriminating SCC from AK and normal skin (Phi coefficient = 0.84). AK could be discriminated from normal skin in both imaging modes by the presence of alternating hyperkeratosis/parakeratosis in cross-sectional mode and/or variability in shape, size and reflectivity of cells (atypical honeycomb pattern) in en face mode. Adnexal involvement of AK could be assessed by the disappearance of the typical cocarde image of adnexal epithelium in en face mode. CONCLUSION: This study provides select 3-D HD-OCT features having a potential to discriminate SCC from AK and normal skin. Based on these particular features with high Phi coefficient, a diagnostic algorithm is designed which will be used later in validation studies to determine HD-OCT accuracy in AK/SCC classification.

High-definition optical coherence tomography algorithm for discrimination of basal cell carcinoma from clinical BCC imitators and differentiation between common subtypes.

BACKGROUND: Preliminary studies have described morphological features of basal cell carcinoma (BCC) imaged by high-definition optical coherence tomography (HD-OCT) and suggested that this technique may aid in its diagnosis and management. However, systematic studies evaluating the accuracy of HD-OCT for the diagnosis of BCC are lacking. OBJECTIVE: The aim of this study was to identify three-dimensional (3-D) HD-OCT features able i) to distinguish BCC from clinical BCC imitators and ii) to discriminate between the most common BCC subtypes. Based on these particular features, a diagnostic algorithm will be suggested. METHOD: A total of 50 histopathologically confirmed BCCs (18 superficial, 19 nodular, 13 infiltrative) were imaged by HD-OCT at the centre of the lesion prior to standard surgical excision and subsequent histopathological analysis. Fifty images of clinical BCC imitators were also retrieved as a 'pitfalls' group. RESULTS: The simultaneous presence of grey/dark subepidermal (hemi-spherical) or intradermal lobulated structure(s) presenting a typical cockade feature in both HD-OCT modes was a significant feature for BCC diagnosis. Features discriminating between BCC subtypes were location of the roof of BCC lobules, vascular pattern of the papillary plexus and stretching effect on the stroma. Clinical BCC imitators such as actinic keratosis, compound and intradermal naevi, amelanotic melanoma, sebaceous hyperplasia and small haemangioma could be differentiated from BCC by means of HD-OCT. CONCLUSION: This study provides a thorough description of 3-D HD-OCT features that can permit discrimination of BCC from clinical BCC imitators and differentiation of BCC subtypes. Based on these features, a diagnostic algorithm is proposed which requires additional validation, but enhances current understanding of the morphological correlates of HD-OCT images in skin.

Electrochemotherapy in the treatment of melanoma skin metastases: a report on 31 cases.

INTRODUCTION AND OBJECTIVES: Electrochemotherapy is indicated for the treatment of unresectable cutaneous and subcutaneous tumors. The technique involves the synergistic use of electroporation of cell membranes to increase the cytotoxicity of anticancer drugs delivered to the tumor cells. The aim of this study was to analyze the clinical effectiveness and safety of electrochemotherapy in the treatment of unresectable locoregional recurrent or metastatic melanomas. MATERIAL AND METHODS: We studied 31 patients treated between January 2007 and December 2012. The European Standard Operating Procedures of Electrochemotherapy (ESOPE) were applied in all cases. Treatment response was analyzed as overall patient response (mean response based on results for all lesions treated in a given patient). RESULTS: Response was classified as partial in 49% of patients and complete in 23%. At 1 year, the level of response achieved had been maintained in 17 patients. Disease progression was observed in 28% of the series. Immediate local complications (pain, swelling, erythema) were mild and resolved within 48hours in most cases. Eight patients developed subsequent local complications, such as ulcers and secondary infections associated with necrosis of the lesions. These complications were brought under control with topical treatments. CONCLUSIONS: Electrochemotherapy is a very effective, safe, and efficient treatment for advanced locoregional disease in patients with unresectable melanoma lesions.

Impact of in vivo reflectance confocal microscopy on the number needed to treat melanoma in doubtful lesions.

BACKGROUND: The number needed to treat (NNT) ratio is an effective method for measuring accuracy in melanoma detection. Dermoscopy reduces the number of false positives and subsequently unnecessary excisions. In vivo reflectance confocal microscopy (RCM) is a noninvasive technique that allows examination of the skin with cellular resolution. OBJECTIVES: To assess the impact of RCM analysis on the number of equivocal lesions, assumed to be melanocytic, excised for every melanoma. METHODS: Consecutive patients (n = 343) presenting with doubtful lesions were considered for enrolment. The lesions were analysed by dermoscopy and RCM, with histopathological assessment considered the reference standard. The main outcome was the NNT, calculated as the proportion of equivocal lesions excised for every melanoma. RESULTS: Dermoscopy alone obtained a hypothetical NNT of 3·73; the combination of dermoscopy and RCM identified 264 equivocal lesions that qualified for excision, 92 of which were confirmed to be a melanoma, resulting in an NNT of 2·87, whereas the analysis of RCM images classified 103 lesions as melanoma, with a consequent NNT of 1·12. The difference in the reduction of this ratio was statistically significant between the three groups (P < 0·0001). There was no significant improvement in sensitivity when comparing the combination of dermoscopy and RCM with RCM alone (94·6% vs. 97·8%; P = 0·043). However, the differences between specificities were statistically significant (P < 1 × 10(-6) ), favouring RCM alone. CONCLUSION: The addition of RCM analysis to dermoscopy reduces unnecessary excisions with a high diagnostic accuracy and could be a means for reducing the economic impact associated with the management of skin cancer.

Clinical usefulness of reflectance confocal microscopy in the management of facial lentigo maligna melanoma.

Facial lentigo maligna melanoma can be a diagnostic challenge in daily clinical practice as it has similar clinical and morphological features to other lesions such as solar lentigines and pigmented actinic keratoses. Confocal microscopy is a noninvasive technique that provides real-time images of the epidermis and superficial dermis with cellular-level resolution. We describe 3 cases of suspected facial lentigo maligna that were assessed using dermoscopy and confocal microscopy before histopathology study. In the first case, diagnosed as lentigo maligna melanoma, presurgical mapping by confocal microscopy was performed to define the margins more accurately. In the second and third cases, with a clinical and dermoscopic suspicion of lentigo maligna melanoma, confocal microscopy was used to identify the optimal site for biopsy.

[Palmoplantar dermatoses: Diagnostic approach in primary care]. / Dermatosis palmoplantares: aproximación diagnóstica en atención primaria.

This article addresses the diagnostic challenges of palmoplantar dermatoses (PPD) within the scope of Primary Health Care (PHC). These common skin conditions, encountered in daily practice, exhibit a diverse range of symptoms and morphologies, complicating their diagnosis. They are etiologically classified into infectious inflammatory, non-infectious inflammatory, and hereditary keratodermas. While various dermatoses may affect the palms and soles, few are specific to this area. Notable examples include palmoplantar pustulosis, dyshidrosis, erythema pernio, and Bazex syndrome. Given the high prevalence of dermatological consultations in PHC, this article underscores the significance of PHC professionals' knowledge regarding these conditions. It proposes a diagnostic algorithm to facilitate their management and timely referral.

Multiple primary melanomas: do they look the same?

BACKGROUND: A series of studies has investigated epidemiological, clinical and genetic characteristics of patients with multiple primary melanoma (MPM). However, comparison of the clinical and dermoscopic features of MPM within a given individual has been described only in case reports. OBJECTIVES: To describe the dermoscopic features of MPM for each given patient, and to evaluate the characteristics eventually associated with similar or dissimilar appearance. METHODS: From the databases of three skin-lesion clinics in the U.S.A., Italy and Spain we collected the dermoscopic images of melanomas in patients diagnosed with MPM. RESULTS: Among 58 patients with MPM, we found that 53% of patients had dermoscopically similar melanomas and 47% of patients had dermoscopically different melanomas. In older patients 59% of melanomas were dermoscopically similar vs. 47% in younger patients (P=0·377). Similar thickness was associated with the occurrence of dermoscopically similar melanomas (19/30 cases, 63%; P=0·039). Most (65%) of the synchronous lesions were similar, compared with 36% of nonsynchronous lesions (P=0·029), and most (69%) of the melanomas on sun-damaged skin were similar, vs. 37% of melanomas on nonsun-damaged skin (P=0·015; odds ratio 3·88, 95% confidence interval 1·11-13·98). The percentage of dermoscopically different melanomas was higher in patients with a family history of melanoma (67% vs. 48%). CONCLUSIONS: MPMs in a given patient have almost the same chance of looking dermoscopically similar or different. However, a subset of elderly patients with sun-damaged skin may present multiple, similar, thin melanomas characterized by pigment-network and regression structures.

Inverted follicular keratosis: dermoscopic and reflectance confocal microscopic features.

Inverted follicular keratosis (IFK) is a rare benign tumor which usually appears as a firm papule on the face. The diagnosis is generally made by histopathology because the clinical appearance is difficult to differentiate from other lesions. Dermoscopic features of IFK have not been established to date. Herein we describe the dermoscopic findings of 4 cases of IFK. Radial peripheral hairpin vessels surrounded by a whitish halo arranged around a central white-yellowish amorphous area were observed in 3 cases, and glomerular vessels were present in the central area of one of them. The fourth case also presented a central white amorphous area but showed arborizing vessels. Reflectance confocal microscopy (available in 1 case) revealed a broadened honeycomb pattern, epidermal projections and hairpin and glomerular vessels. To our knowledge this is the first case series describing the dermoscopic features of inverted follicular keratosis and the first confocal microscopy description of this entity.

COD fractionation and biological treatability of mixed industrial wastewaters.

This study was conducted at a centralized wastewater treatment plant that receives discharges from nearly 160 industries. The chemical oxygen demand (COD) was fractionated for two objectives: delineation of the limits of the activated sludge process being used at the plant, and evaluation of the potential environmental impact of the treated effluent. Physico-chemical analyses, respirometric and biodegradation tests, as well as COD fractionation were carried out. Molasses-wastewaters were determined to be the major contribution to the plant. The influent was dark brown in color, with a relatively high content of both organics (2503 mg/L COD) and salts (5459 µS/cm conductivity), but a low biochemical oxygen demand (568 mg/L BOD(5)) and BOD(5)/COD ratio (0.24). The degradability of the organics was limited by the high content of inert soluble COD (S(I)). The COD fractionation pattern was 40-20-40% for S(I), X(I) (inerts) and S(H) (soluble hydrolyzable), respectively. More than 90% BOD(5) removal was obtained, which was sufficient for the plant to meet the national Standards. However, the effluent discharged into the river was intensely colored and polluted (>1000 mg/L COD, >5000 µS/cm), emphasizing the need for legislation regulating COD, color and salinity, and for upgraded treatment methods worldwide for molasses wastewaters.

Seasonal tendencies of microplastics around coral reefs in selected Marine Protected National Parks of Gulf of California, Mexico.

This study focuses on the presence of MPs in the sediment beds around coral reefs of MPNPs in Baja California Sur, México. Based on seasonal sampling results, comparison of MPs from Cabo Pulmo (avg. 680.25 items/100 g-1 d.w) recorded higher values than Espiritu Santo Island (avg. 321.75 items/100 g-1 d.w) from backshore/foreshore regions. Fibrous MPs are the dominant morphotypes followed by fragments and spheres. SEM/EDS analysis revealed that the MPs are altered texturally in surface and is bioavailable to marine organisms independent of size/shape. FTIR analysis indicate different polymers (in %) in the form of PP (70), PET (65), HDPE (59), LDPE (50), PS (30), PC (18), PU (10) and RYN (10). Most of the MPs are secondary in origin resulting from man-made and tourist's activities controlled by wave transportation and tidal currents. Existence of MPs in sediment beds around the coral reefs signals the ways for future investigations.

Impact of bowel obstruction at the time of initial presentation in women with ovarian cancer.

OBJECTIVE: To determine whether the presence of bowel obstruction at the time of initial presentation has any prognostic significance in these women. DESIGN: Retrospective cohort study. SETTING: Dedicated gynaecological oncology service of a large tertiary institution. POPULATION: Women who had a bowel obstruction as part of their initial presentation of ovarian cancer were identified between 1995 and 2007. Each woman was matched with four control women (with disease but no obstruction). METHODS: Women with disease were compared with controls to determine the impact, if any, of bowel obstruction at presentation. Several prognostic variables including bowel obstruction were also evaluated in a Cox proportional hazard model. MAIN OUTCOME MEASURES: Progression-free survival (PFS) and overall survival (OS). RESULTS: Forty-eight women with disease and 192 controls were identified during the study period. The median follow-up period was 19 months among women with disease versus 20 months in controls. No differences were seen in demographics and clinical characteristics of the women. Optimal cytoreduction rate was similar between the two groups (75% versus 78%, P = 0.7). Patients with bowel obstruction had a shorter PFS and OS compared with controls [19 months versus 21 months (P = 0.01) and 22 versus 35 months (P = 0.008)], respectively. Bowel obstruction at presentation was an independent prognostic variable with a hazard ratio of 1.5 (P = 0.009). Other prognostic variables were age, stage and extent of surgical cytoreduction. CONCLUSIONS: Bowel obstruction at the time of initial presentation is an adverse prognostic factor in women with ovarian cancer.

Polytetrafluoroethylene versus polypropylene mesh during laparoscopic totally extraperitoneal (TEP) repair of inguinal hernia: short- and long-term results of a double-blind clinical randomized controlled trial.

PURPOSE: Aim of the study is to compare macroporous (> 1 mm2) polytetrafluoroethylene mesh (LP-PTFE) versus microporous (< 1 mm2) polypropylene mesh (SP-PPL) in terms of postoperative acute and chronic discomfort and pain, difficulty in mesh handling and long-term recurrence rate. METHODS: Fifty-two patients with bilateral hernia were enrolled in this double-blind randomized controlled trial (NCT02023203). Each hernia, in the same patient, was randomized to implant LP-PTFE or SP-PPL mesh during totally extraperitoneal laparoscopic hernia repair. Patients were followed at 7 days, 1, 3, 6, 12 and 60 months after surgery. Visual analog scale (VAS) score was employed to evaluate the outcomes. Student's t test was used in case of normally distributed continuous variables, while the nonparametric Mann-Whitney U test was used in case of not normally distributed variables. Chi square test was used for analysis of categorical variables. RESULTS: Median VAS discomfort score with SP-PPL was significantly higher than LP-PTFE at 1 and 3 months after surgery (p = 0.003 in both cases). LP-PTFE showed significantly lower median score than SP-PPL at 7 days after surgery (p = 0.025) regarding pain at movement. Testicular pain was lower in case of LP-PTFE than SP-PPL at 7 days, 1 and 3 months after surgery (p = 0.005, p = 0.004 and p = 0.004, respectively). LP-PTFE was significantly more difficult to handle (p = 0.001). At 60 months, one recurrence was observed in the LP-PTFE group (p = 1.0000). CONCLUSIONS: LP-PTFE has less postoperative discomfort and pain up to 3 months after surgery, without differences after that period, although it shows more difficulty in handling and recurrences occur even if not statistically significant.