Melanoma Registry of the Spanish Academy of Dermatology and Venereology (REGESMEL): Description and Data in its First Year of Operation. / Registro de Melanoma de la Academia Española de Dermatología y Venereología (REGESMEL): descripción y datos en el primer año de funcionamiento.

INTRODUCTION: The incidence of melanoma is rising in Spain. The prognostic stages of patients with melanoma are determined by various biological factors, such as tumor thickness, ulceration, or the presence of regional or distant metastases. The Spanish Academy of Dermatology and Venereology (AEDV) has encouraged the creation of a Spanish Melanoma Registry (REGESMEL) to evaluate other individual and health system-related factors that may impact the prognosis of patients with melanoma. The aim of this article is to introduce REGESMEL and provide basic descriptive data for its first year of operation. METHODS: REGESMEL is a prospective, multicentre cohort of consecutive patients with invasive cutaneous melanoma that collects demographic and staging data as well as individual and healthcare-related baseline data. It also records the medical and surgical treatment received by patients. RESULTS: A total of 450 cases of invasive cutaneous melanoma from 19 participant centres were included, with a predominance of thin melanomas≤1mm thick (54.7%), mainly located on the posterior trunk (35.2%). Selective sentinel lymph node biopsy was performed in 40.7% of cases. Most cases of melanoma were suspected by the patient (30.4%), or his/her dermatologist (29.6%). Patients received care mainly in public health centers (85.2%), with tele-dermatology resources being used in 21.6% of the cases. CONCLUSIONS: The distribution of the pathological and demographic variables of melanoma cases is consistent with data from former studies. REGESMEL has already recruited patients from 15 Spanish provinces and given its potential representativeness, it renders the Registry as an important tool to address a wide range of research questions.

[Translated article] Reflectance Confocal Microscopy Terminology in Spanish: A Delphi Consensus Study.

The terminology used to describe reflectance confocal microscopy (RCM) findings in both melanocytic and nonmelanocytic lesions has been standardized in English. We convened a panel of Spanish-speaking RCM experts and used the Delphi method to seek consensus on which Spanish terms best describe RCM findings in this setting. The experts agreed on 52 terms: 28 for melanocytic lesions and 24 for nonmelanocytic lesions. The resulting terminology will facilitate homogenization, leading to a better understanding of structures, more standardized descriptions in clinical registries, and easier interpretation of clinical reports exchanged between dermatologists.

Reflectance Confocal Microscopy Terminology in Spanish: A Delphi Consensus Study. / Consenso de terminología en microscopia confocal de reflectancia en español mediante método Delphi.

The terminology used to describe reflectance confocal microscopy (RCM) findings in both melanocytic and nonmelanocytic lesions has been standardized in English. We convened a panel of Spanish-speaking RCM experts and used the Delphi method to seek consensus on which Spanish terms best describe RCM findings in this setting. The experts agreed on 52 terms: 28 for melanocytic lesions and 24 for nonmelanocytic lesions. The resulting terminology will facilitate homogenization, leading to a better understanding of structures, more standardized descriptions in clinical registries, and easier interpretation of clinical reports exchanged between dermatologists.

Clinical Management of Cutaneous Adverse Events in Patients on Chemotherapy: A National Consensus Statement by the Spanish Academy of Dermatology and Venereology and the Spanish Society of Medical Oncology. / Manejo clínico de los eventos adversos cutáneos en pacientes tratados con quimioterapia: consenso nacional de la Academia Española de Dermatología y Venereología y de la Sociedad Española de Oncología Médica.

Although the arrival of new chemotherapy drugs and combinations has brought progress in terms of cancer patient survival, they entail many adverse effects that can compromise treatment, and hence prognosis, of the disease. Cytostatic agents can cause dermatological toxicity, among other side effects. The most familiar adverse effect of chemotherapy is alopecia. Although not serious, this changes the outward appearance of cancer patients. Other adverse effects include hypersensitivity and photosensitivity reactions, hand-foot syndrome, epidermal necrolysis, recall reactions, scleroderma-like reactions, Raynaud's phenomenon, eccrine squamous syringometaplasia, neutrophilic eccrine hidradenitis, nail abnormalities, pigmentation changes and extravasation injuries. Onset of these adverse effects often causes dose reduction and/or delayed treatment, which can affect patient survival and quality of life. It is therefore important to prevent their occurrence and treat them promptly, which requires cooperation between medical oncologists and dermatologists. This article reviews chemotherapy-associated dermatological toxicity, along with its diagnosis and therapeutic management.

Clinical management of cutaneous adverse events in patients on targeted anticancer therapies and immunotherapies: a national consensus statement by the Spanish Academy of Dermatology and Venereology and the Spanish Society of Medical Oncology.

Progress in the understanding of many tumors has enabled the development of new therapies, such as those targeted at specific molecules involved in cell growth (targeted therapies) or intended to modulate the immune system (immunotherapy). However, along with the clinical benefit provided by these new treatments, new adverse effects have also appeared. Dermatological toxicities such as papulopustular eruptions, xerosis, and pruritus are common with EGFR inhibitors. Other adverse effects have also been described with PDGFR, BCR-ABL, and MAPK tyrosine kinase inhibitors, antiangiogenic drugs, and inhibitors at immune checkpoints such as CTLA-4 and PD-1/PD-L1. Onset of these adverse effects often causes dose reductions and/or delays in administering the prescribed therapy, which can affect patient survival and quality of life. It is, therefore, important to prevent the occurrence of these adverse effects, or to treat unavoidable ones as soon as possible. This requires cooperation between medical oncologists and dermatologists. This article reviews the various dermatological toxicities associated with targeted therapies and immunotherapies, along with their diagnosis and therapeutic management.

Cutaneous toxicities of new treatments for melanoma.

New drugs against advanced melanoma have emerged during last decade. Target therapy and immunotherapy have changed the management of patients with metastatic disease. Along with its generalized use, drug toxicities have appeared and the skin is the target organ of a significant part of them. This revision summarizes the most common side effects and consensus management to improve the compliance of therapies and patients' quality of life. Among the BRAF inhibitors, main cutaneous side effects are photosensitivity, plantar hyperkeratosis, and the appearance of verrucal keratosis or squamous cell carcinoma. Special attention must be paid to the development of new primary melanomas or changes on nevi during BRAF inhibitor therapy. The most common cutaneous side effects of immunotherapy are rash, pruritus, and vitiligo. It remains controversial the possible role of these toxicities as markers of response to therapy.

Diagnostic and prognostic contribution of laryngeal electromyography in unilateral vocal-fold immobility in adults.

OBJECTIVES: To study the diagnostic and prognostic contribution of laryngeal electromyography in unilateral vocal-fold immobility in adults. MATERIAL AND METHODS: A retrospective study included patients with unilateral vocal-fold immobility undergoing laryngeal electromyography between 2007 and 2015. Neurogenic, normal or myogenic findings were compared to the clinical aspect. Prognosis for recovery was assessed from motor unit potentials on laryngeal electromyography, and compared to subsequent progress on laryngoscopy. RESULTS: Sixty-three patients (mean age, 59 years) were initially included; 2 were subsequently excluded from analysis. Mean time from onset of immobility to laryngeal electromyography was 7 months. 85% of the 61 patients showed neurogenic findings, indicating neural lesion; 13% showed normal electromyography, indicating cricoarytenoid joint ankylosis; and 1 patient showed a myogenic pattern. Neurogenic cases were usually secondary to cervical surgery. Thirty-eight patients were followed up. In total, 75% of patients showing reinnervation potentials recovered. The positive predictive value of laryngeal electromyography was 69.2%. CONCLUSION: Laryngeal electromyography is effective in specifying the origin of unilateral vocal-fold immobility in adults. It also has a prognostic role, lack of reinnervation potentials being a possible indication for early medialization surgery.

In vivo reflectance confocal microscopy characterization of silver deposits in localized cutaneous argyria.

Localized cutaneous argyria is a rare condition secondary to skin deposition of silver following exposure to substances containing this metal. The clinical appearance and dermoscopy findings require deep melanocytic lesions and particularly melanoma metastasis to be ruled out. Silver deposits are usually confirmed by scanning electron microscopy and/or energy-dispersive X-ray spectroscopy. Herein we describe the in vivo reflectance confocal microscopy (RCM) features observed in one case of localized cutaneous argyria. These features include the presence of a hyperrefractile network in the papillary dermis and a periadnexal dotted bright pattern. In vivo RCM might be a useful tool for an early diagnosis of this uncommon entity.

Oral self-administration of buprenorphine in the diet for analgesia in mice.

Postsurgical oral self-administration of analgesics in rodents is an interesting technique of providing analgesia, avoiding the negative effects of manipulation. Several strategies, using gelatin or nutella, have already been described. However, rodents require some habituation period to reach a good intake because of their neophobic behavior. The current study aimed to explore whether buprenorphine when mixed with an extruded diet offers a potential treatment option in the pain management of mice using a triple approach: by measuring the spontaneous intake in healthy animals; by using the hot-plate test; and finally by assessing the drug's ability to provide postoperative analgesia in a surgical intervention of moderate severity (intra-utero electroporation). Mice consumed during 20 hours, similar amounts of extruded diet alone, mixed with glucosaline, and mixed with buprenorphine (0.03 mg per pellet) or meloxicam (0.25 mg per pellet) both of which were diluted in glucosaline, showing that no neophobia was associated with these administrations. Relative increase from baseline latency (% maximal possible effect) in the hot-plate test at 20 h of administration was significantly higher for oral buprenorphine in diet 0.03 mg/pellet, and diet 0.15 mg/pellet, compared with placebo and no differences were found between those oral administrations and subcutaneous buprenorphine 0.1 mg/kg measured 3 h later. The treatment was also effective in attenuating the reductions in food consumption and body weight that occur after surgery. These data suggest that providing buprenorphine with the diet is a feasible and effective way of self-administration of analgesia in mice and does not cause neophobia and may easily contribute to the refinement of surgical procedures.

Surveillance for treatment failure of lentigo maligna with dermoscopy and in vivo confocal microscopy: new descriptors.

BACKGROUND: Nonsurgical treatment (radiotherapy, imiquimod) is increasingly employed for the management of lentigo maligna (LM). While the diagnosis of LM remains difficult, the detection of treatment failure is even more challenging. OBJECTIVES: To describe the sensitivity and specificity for the diagnosis of LM of individual features and methods using dermoscopy and in vivo reflectance confocal microscopy (RCM) to aid in the detection of treatment failure of LM following nonsurgical treatment. METHODS: A retrospective study of dermoscopy and RCM images (blinded to the correlation with pathology) in patients with biopsy-confirmed LM who were undergoing nonsurgical treatment in two referral institutions - one in Sydney, Australia, and the other in Barcelona, Spain. Ninety-eight patients were treated nonsurgically for LM during the period 2006-2012. Thirty-one patients had abnormal dermoscopy or RCM evaluation, and had a biopsy that identified LM recurrence in 15 patients and nonmelanoma diagnoses in 16 patients (one Bowen disease, 15 solar changes). RESULTS: The diagnosis of treatment failure was difficult with dermoscopy, with a sensitivity of 80% and specificity of 56%, even with the interpretation of an expert. The best criterion was asymmetric hyperpigmented follicular openings, but this was present in only 47% of treatment failure LM. Isolated, very fine brown dots ('dust' appearance) correlated highly with the diagnosis of treatment failure LM (73% sensitivity and 88% specificity) and with pagetoid cells seen with RCM. The LM score, comprising six criteria, had a specificity of 94% and sensitivity of 100%. CONCLUSIONS: These methods and descriptors should help to manage the diagnosis of treatment failure.

Evaluation of MYC status in oral lichen planus in patients with progression to oral squamous cell carcinoma.

BACKGROUND: Malignant transformation of oral lichen planus (OLP) to oral squamous cell carcinoma (OSCC) is controversial. C-MYC is a proto-oncogene involved in various solid tumours, including OSCC. OBJECTIVES: To determine MYC status using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in OLP lesions from 10 patients with progression to OSCC (group I) and to compare this with OLP lesions from patients without progression to OSCC (group II). METHODS: We constructed two tissue microarrays with 11 OSCC samples (group IA), 17 OLP samples from the same patients (group IB) and 13 OLP specimens from 12 control patients (group II). FISH evaluation of the MYC gains was determined in 100 nonoverlapping nuclei per sample. IHC evaluation was determined by calculating the percentage C-MYC expression in the epithelial cells. RESULTS: OSCC samples showed MYC copy number gains and C-MYC overexpression in 91% and 73% of cases, respectively. MYC gains were detected in 47% of samples from group IB and were absent from all samples from group II. C-MYC was overexpressed in 87% of cases from group IB and in only 44% of control specimens (group II). The differences in MYC status between groups IB and II were statistically significant. CONCLUSIONS: OLP lesions in patients with progression to OSCC show MYC gains and C-MYC overexpression. In patients with severe OLP, determining MYC status may predict a subgroup of subjects with a higher risk of progression to OSCC.

Ser agente de salud y el cuidado humanitario. Contribuyendo a su transformación / Being a health agent and the humanitarian care. Con- tributing to its transformation

El cuidado humanitario es un acto del ser, susceptible de evolucionar y conformar una unidad de cuidado a la salud con calidad para todos y requiere también de cuidado para no perder su valor de sentido positivo. Conciliar teoría y práctica no es simple, sino complejo. En este artículo se propone atender la relación Agente de Salud­Paciente por ser universal y congruente con el cambio. El enfoque epistemológico puntualiza lo positivo, lo acumulado en la historia no puede desaparecer del presente. La respuesta es integración, hacer coincidir las ciencias formales, con las sociales, humanas y la tecnología. El apoyo cultural es vital, la educación es sólo parte y convoca a construir el nuevo paradigma; al invocarlo se superan las acciones ineficaces. El acto preventivo es a todos los niveles, sea del hospital, la escuela, la comunidad el hogar y la comunidad entera. La Enfermería del futuro, con su desarrollo teórico, contribuye al cambio, del cuidado reduccionista al integral y humanitario. Se propone reforzar la atención al desempeño del Agente de Salud y orientarlo con la disposición Humanitaria. El tema profundiza en el conocimiento del cuidado y le concierne a todo profesional de la salud.

The humanitarian care is an act, the being who may evolve and transformed into a quality unit for everybody's health care. Requires attention, good care, and not to lose the sense of positive value. Must reconcile theory and practice which is not so simple, it is rather complex. We propose to address the Relationship of Health Agent - Patient to a universal approach consistent with the changing nature. The epistemological approach points out the positive sense. The history accumulated knowledge cannot fail at the present time. The answer is integration, to combine formal sciences with social and human, as well as technology. The cultural support is vital for education and is part of it, calls for the build the new paradigm. To invoke it is sufficient to avoid ineffectiveness. The preventive act is at all levels, whether in hospital, school, community, home and the entire community. The future nursing, with the care models, should contribute to shift from the reductionist care to the humanitarian care. Let us reinforce the Health Agent performance and guide it towards a Humanitarian Care. The issue analyzes the care knowledge and is of every health server concern.

Non-invasive management of non-melanoma skin cancer in patients with cancer predisposition genodermatosis: a role for confocal microscopy and photodynamic therapy.

BACKGROUND: Patients with genodermatosis such as Gorlin syndrome (GS) and Xeroderma pigmentosum (XP) require a close follow-up for early diagnosis and treatment of skin cancer. We aimed to evaluate the efficacy of methyl-aminolevulinate (MAL) photodynamic therapy (PDT) in basal cell carcinomas (BCCs) from patients with GS and XP, and to determine the utility of reflectance confocal microscopy (RCM) in the diagnosis and the evaluation of therapeutic response. PATIENTS AND METHODS: We included four patients with GS and two siblings with XP. Single or multiple lesions in localized areas were treated with 1-3 cycles of MAL PDT. RCM was performed before and 3 months after the treatment in target lesions in all the patients. Patients were followed up for 3 years. RESULTS: In XP patients, we treated 13 pigmented BCCs on the face. All the lesions responded to the treatment and six lesions showed a complete clinical clearing. In GS patients, facial or trunk areas with multiple BCCs were treated (up to 200). Complete clinical remission was obtained in 25-67% of the lesions. Some nodular and pigmented lesions failed to achieve a complete remission. RCM could identify already described confocal features for BCC. Tumour remissions could be assessed by this technique. CONCLUSIONS: Methyl-aminolevulinate PDT may be useful for the treatment of superficial BCC in GS and XP. In some nodular lesions, PDT may complement surgery reducing tumour size. RCM may be regarded in the future as a complementary technique in BCC for the diagnosis and post-treatment assessment to non-invasive therapeutic modalities.

[ECMO: experience in paediatrics]. / ECMO: experiencia en edad pediátrica.

INTRODUCTION: ECMO (Extracorporeal Membrane Oxygenation) provides a vital support to patients with supposed reversible respiratory and/or cardiac failure, in whom conventional support techniques have been previously unsuccessful. OBJECTIVES: To determinate the criteria used in our hospital to put paediatric patients on ECMO, compare their clinical course depending on their pathology (respiratory failure, congenital heart disease or sepsis) and identify the sequelae attributable to this technique. MATERIAL AND METHOD: A retrospective review of clinical records of all patients on ECMO support in our centre, excluding those presenting typically in neonatal period. RESULTS: ECMO was used on 16 patients from June 2001 to January 2007, of which 50% were males. The median age was 7 months (from 21 days to 11 years). The reason for starting ECMO was respiratory failure in 11 cases (oxygenation index >40 and/or alveolar-arterial oxygen gradient >605), congenital heart disease in 2 and sepsis in 3 (due to shock unresponsive to adequate resuscitation). The median time to starting ECMO from PICU admission was 3.58 days (from 12h to 9 days). Venovenous cannulation was used initially in 8 patients, but 5 of them needed venoarterial ECMO later. The technique was used for a mean of 8 days (from 1 to 28 days). The main complication was the isolation of bacteria in different cultures (8 patients). The overall survival was 50% (6 patients with respiratory failure and both patients submitted to cardiac surgery). Extracorporeal support was withdrawn in 7 children because their clinical situation was irreversible. Another patient died seven days after successful decannulation. We have not found any serious sequel among survivors that could be attributable to this technique. CONCLUSIONS: Survival among children supported with ECMO in our hospital is similar to that recorded by the ELSO in 2004, although the prognosis depends on the initial pathology. There are different criteria for starting this technique depending on the underlying diseases: respiratory index of poor prognosis in patients with respiratory failure, haemodynamic instability in those with sepsis or cardiac failure after cardiovascular surgery. We have not found any serious sequel among the survivors which could be attributable to this technique.

Delignificación selectiva del pasto pennisetum purpureum x pennisetum typhoides usando basidiomicetos ligninolíticos / Selective delignification of the pennisetum purpureum x pennisetum typhoides grass using ligninolytic basidiomycetes

Muestras de pasto Pennisetum purpureum x Pennisetum typhoides de 120 días de corte se someten durante siete semanas a fermentación selectiva en estado sólido (FES) con cepas de Ganoderma ssp y Lentinus ssp. Se realiza la caracterización de la delignificación por Infrarrojo con Transformada de Fourier (IR-TF) midiendo las áreas de las principales bandas características. Mediante esta técnica se establece que las muestras tratadas con Ganoderma spp se obtiene una pérdida del 70 por ciento de los compuestos aromáticos con relación a los alifáticos. En las semanas cero y séptima se establecieron valores de lignina en detergente ácido (LDA) 55.9 por ciento y 10.7 por ciento, respectivamente. En este mismo periodo los contenidos de materia seca y celulosa variaron del 73.3 por ciento al 92.9 por ciento y del 3.1 por ciento al 51.7 por ciento respectivamente. Estos resultados confirman una degradación selectiva de la lignina en las muestras tratadas con Ganoderma spp y medios suplementados con manganeso. Las pruebas de degradabilidad in situ, utilizando la técnica de la bolsa de nailon y de digestibilidad in vitro de la materia seca basada en técnicas enzimáticas y gravimétricas, no mostraron mejoramiento de la digestibilidad del pasto como consecuencia de la fermentación con las dos cepas de hongos basidiomicetos, corroborando lo indicado por otros autores que afirman que los hongos puede ser tóxicos para la microflora del rumen y, por lo tanto, pueden la digestibilidad de la materia seca

Eosinophilic ulcer of the oral mucosa: a distinct entity or a non-specific reactive pattern?

Eosinophilic ulcer of the oral mucosa (EUOM) is an uncommon self-limited oral condition that clinically manifests as a solitary ulceration with elevated indurate borders affecting the tongue, buccal mucosa or lip. Microscopically, it is characterized by a polymorphic inflammatory infiltrate with a prominent polymorphonuclear eosinophilic component extending deep into the submucosa, underlying muscle and salivary glands. Large mononuclear cells probably corresponding to histiocytes, myofibroblasts or activated lymphoid cells are also frequently observed. The exact pathogenetic mechanisms implicated in the development of EUOM are poorly understood; however, the possibility that trauma may play a role in its development has been often postulated. Since its original description, the possibility that EUOM could be either considered an individualized disorder or a non-specific reactive pattern secondary to several stimuli has been discussed. EOUM may show some overlapping features with some entities such as atypical histiocytic granuloma, mucosal angiolymphoid hyperplasia with eosinophilia, and Kimura disease. The clinical and histopathological features and the differential diagnosis of EUOM are reviewed and its existence as a distinct disease discussed.

[Late-onset familial amyloid polyneuropathy in the Safor (Valencia) area: four case reports]. / Polineuropatía amiloidótica familiar de presentación tardía en la comarca de la Safor (Valencia): presentación de 4 casos.

Four cases of late onset familial amyloid polyneuropathy diagnosed in relatively advanced ages and within 3 families of our area where the disease had never been described are presented. The possible origin of the mutation and need to consider this diagnosis even when there is no known family background or when the age of presentation is late are commented. The nerve biopsy does not always show the deposits as these are patchy and DNA studies or detection of abnormal TTR in serum are necessary for the diagnosis.