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The aim of the present study was to evaluate the presence of microplastics in drinking water along a large distribution water supply network. Tap water was collected in situ at sampling cabinets using an in-line sampling procedure that provided a representative sample with minimal risk of external contamination and avoided the transportation of large volumes to the laboratory. Microplastics > 50 μm were analysed via Fourier transform infrared spectroscopy (FTIR). Microplastics were detected in 38% of samples with a mean concentration of 0.01 microplastics per litre and polymers identified were polypropylene (PP), polyester (PES) and polyamide (PA). Detection of polytetrafluoroethylene (PTFE) and silicone particles were associated to the maintenance of cabinets. This study contributes to increase the knowledge regarding the presence and behaviour of microplastics throughout a large drinking water supply network providing water to 3 000 000 inhabitants. Results indicate that the pipes and the supply network not release microplastics into the drinking water., This work has been financed by the project ‘Microplastics in drinking water’ from Aigües de Barcelona and by the Ministry of Science and Innovation of Spain under the project PID2019-105732GB-C21. Joan Dalmau-Soler acknowledges the support of Industrial Doctorates Plan of the University and Research Secretary of the Economy and Knowledge Department of the Generalitat de Catalunya. The authors also are grateful to M. Paraira, J. Martin, M. Minoves and the members of Organic Chemistry Department for their support and advice.

Nowadays, the presence of microplastics in drinking water is of concern worldwide due to potential impacts on human health. This paper has examined the presence of microplastics along the Llobregat river basin (Catalonia, Spain) and studied their behaviour and elimination along the drinking water treatment plant (DWTP). Due to different water composition, different sampling and sample preparation protocols were used to determine microplastics from river water and in the DWTP. Identification of microplastics of size range from 20 μm to 5 mm was performed by fourier-transform infrared spectroscopy (FTIR). Microplastics were detected in 5 out of 7 points along the Llobregat basin, with concentrations ranging between non-detected and 3.60 microplastics/L. In the intake of the DWTP, the mean concentration was 0.96 ± 0.46 microplastics/L (n=5), with a predominance of polyester (PES) and polypropylene (PP) and at the outlet the mean concentration was of 0.06 ± 0.04 microplastics/L with an overall removal efficiency of 93 ± 5%. Sand filtration was identified as the key stage in microplastic removal (78 ± 9%). Furthermore, the results showed that ultrafiltration/reverse osmosis (advanced treatment) is more effective for microplastic removal than ozonation/carbon filtration stage (upgraded conventional treatment). In addition, a preliminary migration test of the different materials used in the DWTP has been performed to identify potential sources of microplastics in each treatment step., The authors are grateful to J. Martin, M. Minoves who provided advise and information where to sample in the DWTP and on the materials used in the treatment process, and arranged and adapted the pump to eliminate the plastic parts; M. Ganzer, S. Montes for assistance, help and for providing all the facilities to sample and extract microplastics in the DWTP; P. Hermo for assisting in the microplastic analysis with FTIR; F. Sanchez, X. Pardo, A. Vilaplana, C. Vega, I. García for their technical support and the members of Organic Chemistry Department for advise during the study. The authors thank the support of Industrial Doctorates Plan of the University and Research Secretary of the Economy and Knowledge Department of the Generalitat de Catalunya. SL acknowledges the Ministry of Science and Innovation of Spain under the project PID2019-105732GB-C21.

Proliferative nodules (PNs) are benign nodular proliferation of melanocytes occurring within congenital melanocytic naevi (CMN). Differential diagnosis between PN and melanoma is challenging for clinicians and pathologists. We describe the case of a 9-month-old boy who developed multiple nodules arising in a medium-sized CMN. Clinically, pink papules were observed, with dotted vessels on dermoscopy, suggesting spitzoid PN. On histopathological examination, the dermoscopic findings correlated with the vertical vessels of a spitzoid PN. Dermoscopy could be a useful tool to differentiate PN from melanoma. However, further studies describing the dermoscopic features of the different PN subtypes are needed. Histopathology remains the gold standard for definitive diagnosis aided by ancillary molecular tests such as fluorescence in situ hybridization or comparative genomic hybridization.

BackgroundIn patients with obstructive sleep apnoea (OSA), intermittent hypoxia induces overexpression of paraspeckle component (PSPC)1, a master modulator of transforming growth factor (TGF)-β signalling, which promotes cell cancer progression through epithelial–mesenchymal transition (EMT) and acquisition of cancer stem cell (CSC)-like features. However, the persistence of intermittent hypoxia-induced effects on PSPC1, and their consequences in cancer patients are not known. To this effect, circulating PSPC1 levels were compared in patients with cutaneous melanoma with or without OSA, and their relationship with tumour aggressiveness along with thein vitroeffects of soluble PSPC1 and intermittent hypoxia on melanoma cell aggressiveness mechanisms were assessed.MethodsIn 292 cutaneous melanoma patients, sleep studies and serum levels of PSPC1 and TGF-β were evaluated. The effect of PSPC1 on expression of EMT and CSC transcription factors was assessed using melanoma cell lines with patient sera under both normoxia and intermittent hypoxia conditions.ResultsPSPC1 levels were higher in patients with moderate–severe OSA compared with mild OSA or non-OSA patients. Serum levels of PSPC1 were associated with several cutaneous melanoma clinical aggressiveness indicators. Both intermittent hypoxia exposures and serum from OSA patients upregulated TGF-β expression and amplified the expression of transcription factors associated with EMT activation and acquisition of CSC characteristics.ConclusionIn cutaneous melanoma patients, OSA severity is associated with higher PSPC1 serum levels, which jointly with intermittent hypoxia would enhance the self-reprogramming capabilities of EMT and CSC feature acquisition of melanoma cells, promoting their intrinsic aggressiveness.

The incidence of melanoma has been increasing worldwide during recent decades. The objective of the study was to analyse the trends in incidence for in situ and invasive melanoma in the Spanish region of Catalonia during the period of 2008-2017. We designed a cross-sectional study with an age-period-cohort analysis of melanoma patient data from the Network of Melanoma Centres in Catalonia. Our database covered a population of over seven million and included a total of 8626 patients with incident melanoma. The main outcome measures were crude and age-standardised incidence rates to the European 2013 standard population. Joinpoint regression models were used to evaluate the population trends. We observed an increase in the age-standardised incidence rate (per 100,000 population) of all melanoma subtypes from 11.56 in 2008 to 13.78 in 2017 with an average annual percent change (AAPC) of 3.5%. This incidence increase was seen exclusively in the older population. Moreover, the stratified analysis showed a statistically significant increase in the age-standardised incidence rate for invasive (AAPC 2.1%) and in situ melanoma (AAPC 6.5%). In conclusion, the incidence of melanoma has continued to increase in the elderly population over recent decades, with a rapidly increasing trend of in situ melanomas and the lentigo maligna subtype. The study in the Melanoma Unit, Hospital Clínic, Barcelona was supported in part by grants from Fondo de Investigaciones Sanitarias P.I. 12/00840, PI 15/00956, and PI 15/00716 Spain; by the CIBER de Enfermedades Raras of the Instituto de Salud Carlos III, Spain, co-funded by “Fondo Europeo de Desarrollo Regional (FEDER). Unión Europea. Una manera de hacer Europa”; by the AGAUR 2014_SGR_603 and 017_SGR_1134 of the Catalan Government, Spain; by a grant from “Fundació La Marató de TV3, 201331-30”, Catalonia, Spain; by the European Commission under the 6th Framework Programme, Contract no : LSHC-CT-2006-018702 (GenoMEL); by CERCA Programme/Generalitat de Catalunya; by a Research Grant from “Fundación Científica de la Asociación Española Contra el Cáncer” GCB15152978SOEN, Spain; by a grant from the European Academy of Dermatology and Venereology (EADV) (PPRC-2017/19). Part of the work was developed at the building Centro Esther Koplowitz. Melanoma research at the Department of Dermatology of Hospital Universitari Arnau de Vilanova de Lleida is supported by grants from ISCIII (PI15/00711 to RMM, cofinanced by FEDER “Una manera de hacer Europa” and CIBERONC- CB16/12/00231) and from Fundació la Marató de TV3 (FMTV 201331-31 to RMM).

Active transforming growth factor-β1 (TGF-β1), a cytokine partially regulated by hypoxia and obesity, has been related with poor prognosis in several tumors. We determine whether obstructive sleep apnea (OSA) increases serum levels of active TGF-β1 in patients with cutaneous melanoma (CM), assess their relationship with melanoma aggressiveness and analyze the factors related to TGF-β1 levels in obese and non-obese OSA patients. In a multicenter observational study, 290 patients with CM were underwent sleep studies. TGF-β1 was increased in moderate-severe OSA patients vs. non-OSA or mild OSA patients with CM. In OSA patients, TGF-β1 levels correlated with mitotic index, Breslow index and melanoma growth rate, and were increased in presence of ulceration or higher Clark levels. In CM patients, OSA was associated with higher TGF-β1 levels and greater melanoma aggressiveness only in non-obese subjects. An in vitro model showed that IH-induced increases of TGF-β1 expression in melanoma cells is attenuated in the presence of high leptin levels. In conclusion, TGF-β1 levels are associated with melanoma aggressiveness in CM patients and increased in moderate-severe OSA. Moreover, in non-obese patients with OSA, TGF-β1 levels correlate with OSA severity and leptin levels, whereas only associate with leptin levels in obese OSA patients., This study was supported by Grants from Fondo de Investigación Sanitaria (FIS) and Fondos FEDER PI16/00201 and PI19/01612 to F. García-Río, PI19/01363 to C. Cubillos-Zapata and PIE15/00065 to E. López-Collazo. M.A. Martínez-García is supported by the Spanish Ministry of Economy and Competitiveness—Instituto de Salud Carlos III (FIS 2016/ 01772) and co-financed by the European Development Regional Fund. A way to achieve Europe (ERDF). DG is supported in part by National Institutes of Health grants HL130984 and HL140548.

Background Recent epidemiological studies suggest that past data where superficial spreading melanoma was by far the most common subtype of melanoma may not reflect current patterns of sun exposure or other risk factors more involved in other subtypes of melanoma as lentigo maligna (LM) or lentigo maligna melanoma (LMM). Methods In order to measure the current situation in our country, all cases of LM and LMM diagnosed in 23 hospitals in Catalonia, from 2000 to 2007, were recorded. Results Although for the global period LM/LMM represented only 8.4% of cases, an increasing trend in this percentage was observed throughout the study period (from 6.9% [27 cases] in 2000 to 13.1% [94 cases] in 2007). Also, an increasing incidence of LM/LMM was observed, especially in chronically sun-exposed areas (85.5% involving the head and neck region). During the 8 years of the registry, the mean Breslow thickness of LMM remained stable. However, the increase in the number of LM (in situ) cases was significantly higher than the increase of the invasive ones. Conclusions An important observation from this data is that aging of population and current sun exposure patterns could keep increasing the incidence of LM/LMM, which may become an important public healthcare problem, over the other histological subtypes. In order to establish primary or secondary preventive measures to the LM/LMM risk-population, it is imperative to highlight the importance of chronic sun damage as a melanoma risk factor, and not only sunburn, most commonly addressed in melanoma prevention campaigns.

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 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.

Midkine (MDK) might mediate the proangiogenic effect of intermittent hypoxia (IH) in patients with obstructive sleep apnea (OSA) and cutaneous melanoma (CM). We compare circulating MDK in CM patients with and without OSA, and their relationship with tumor aggressiveness, while exploring in vitro effects of soluble MDK on human lymphatic endothelial (HLEC) and melanoma cell proliferation. In 360 CM patients, sleep studies and MDK serum level measurements were performed. The effect of MDK on cell proliferation was assessed using HLEC and melanoma cell lines with patient sera under both normoxia and IH. MDK levels were higher in severe OSA compared to mild OSA or non‐OSA patients, whereas no differences in VEGF levels emerged. In OSA patients, MDK levels correlated with nocturnal hypoxemia and CM mitotic rate. In vitro, MDK promotes HLEC proliferation under IH conditions. Moreover, cultures of the human melanoma cell line C81‐61 with sera from patients with the highest MDK levels promoted tumor cell proliferation, which was attenuated after the addition of MDK antibody. These responses were enhanced by IH exposures. In conclusion, in CM patients, OSA severity is associated with higher MDK levels, which, appear to enhance both the lymphangiogenesis as the intrinsic aggressiveness of CM tumor cells., Fondo de Investigación Sanitaria‐Fondos FEDER. Grant Numbers: PI13/01512, PI16/00201, PI14/01234, PIE15/00065, PI16/01772 HHS | National Institutes of Health (NIH). Grant Numbers: HL130984, HL140548

Obstructive sleep apnoea (OSA) upregulates the programmed cell death-1 receptor and its ligand (PD-L1) pathway, potentially compromising immunosurveillance. We compared circulating levels of soluble PD-L1 (sPD-L1) in patients with cutaneous melanoma according to the presence and severity of OSA, and evaluated relationships with tumour aggressiveness and invasiveness.In a multicentre observational study, 360 patients with cutaneous melanoma underwent sleep studies, and serum sPD-L1 levels were assayed using ELISA. Cutaneous melanoma aggressiveness indices included mitotic rate, Breslow index, tumour ulceration, Clark level and tumour stage, and sentinel lymph node (SLN) metastasis was recorded as a marker of invasiveness.sPD-L1 levels were higher in severe OSA compared to mild OSA or non-OSA patients. In OSA patients, sPD-L1 levels correlated with Breslow index and were higher in patients with tumour ulceration, advanced primary tumour stages or with locoregional disease. The incorporation of sPD-L1 to the classic risk factors to SLN metastasis led to net improvements in the classification of 27.3%.Thus, sPD-L1 levels are increased in melanoma patients with severe OSA, and, in addition, might serve as a potential biomarker of cutaneous melanoma aggressiveness and invasiveness in this group of subjects.

All cases of MM diagnosed in 23 hospitals in Catalonia, from 2000 to 2007 were recorded and melanoma incidence calculated and adjusted for the European standard population via the direct method. The age standardised rate/100,000 inhabitants varied from 6.74 in 2000 to 8.64 in 2007 for all melanomas and from 4.79 to 5.80 for invasive MMs; the Breslow thickness was stable during the period. The increase in invasive melanoma incidence in the elderly was remarkable, the crude rate/100,000 inhabitants increasing from 11.04 (2000) to 15.49 (2007) in the 60-64 year population, while remaining more stable in the 30-34 year range, from 3.97 in 2000 to 4.55 in 2007, and with a tendency to decrease from 5.1 in 2000 to 2.5 in 2007 for the age range of 25-29 years. These lower age ranges are much more affected by immigration. Despite the large immigrant population (nearly one million immigrants arrived in Catalonia during the study period from countries with a low melanoma incidence), melanoma incidence in our region has risen considerably and this trend is likely to persist in the near future. The research at the Melanoma Unit in Barcelona is partially funded by Grants 03/0019, 05/0302, 06/0265, 09/1393 and 12/00840 from Fondo de Investigaciones Sanitarias, Spain, co-funded by “Fondo Europeo de Desarrollo Regional (FEDER). Unión Europea. Una manera de hacer Europa”; by the CIBER de Enfermedades Raras of the Instituto de Salud Carlos III, Spain; by the AGAUR 2009 SGR 1337 of the Catalan Government, Spain; by the European Commission under the 6th Framework Programme, Contract nº: LSHC-CT-2006-018702 (GenoMEL) and by the National Cancer Institute (NCI) of the US National Institute of Health (NIH) (CA83115).

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.

The consensus statement on the management of primary cutaneous melanoma that we present here was based on selection, discussion, review, and comparison of recent literature (including national and international guidelines). The protocols for the diagnosis, treatment, and follow-up used in the hospital centers throughout Catalonia and the Balearic Isles belonging to the Network of Catalan and Balearic Melanoma Centers were also considered. The main objective of this statement was to present the overall management of melanoma patients typically used in our region at the present time. As such, the statement was not designed to be an obligatory protocol for health professionals caring for this group of patients, and neither can it nor should it be used for this purpose. Professionals reading the statement should not therefore consider it binding on their practice, and in no case can this text be used to guarantee or seek responsibility for a given medical opinion. The group of dermatologists who have signed this statement was created 3 years ago with the aim of making our authorities aware of the importance of this complex tumor, which, in comparison with other types of cancer, we believe does not receive sufficient attention in Spain. In addition, the regular meetings of the group have produced interesting proposals for collaboration in various epidemiological, clinical, and basic applied research projects on the subject of malignant melanoma in our society.

The consensus statement on the management of primary cutaneous melanoma that we present here was based on selection, discussion, review, and comparison of recent literature (including national and international guidelines). The protocols for the diagnosis, treatment, and follow-up used in the hospital centers throughout Catalonia and the Balearic Isles belonging to the Network of Catalan and Balearic Melanoma Centers were also considered. The main objective of this statement was to present the overall management of melanoma patients typically used in our region at the present time. As such, the statement was not designed to be an obligatory protocol for health professionals caring for this group of patients, and neither can it nor should it be used for this purpose. Professionals reading the statement should not therefore consider it binding on their practice, and in no case can this text be used to guarantee or seek responsibility for a given medical opinion. The group of dermatologists who have signed this statement was created 3 years ago with the aim of making our authorities aware of the importance of this complex tumor, which, in comparison with other types of cancer, we believe does not receive sufficient attention in Spain. In addition, the regular meetings of the group have produced interesting proposals for collaboration in various epidemiological, clinical, and basic applied research projects on the subject of malignant melanoma in our society.

The quadratus femoris is an external rotator of the hip. Quadratus femoris injury can accompany damage to the surrounding muscles. Guided by the clinical symptoms, the injection technique described here can facilitate accurate diagnosis in selected cases.

El diagnostico del sindrome del canal carpiano, frecuente, rara vez va mas alla de un estudio clinico y electromiografico. Presentamos el caso de una mujer de 60 anos diagnosticada de amiloidosis AL primaria sistemica muchos anos despues de que se hubiera manifestado el sindrome del canal carpiano

BACKGROUND Acral melanoma may adopt a variety of clinical characteristics simulating other tumors, ulcers, hemorrhage, or infections. In the Caucasian population health care providers often misdiagnose acral melanoma, and this is the cause of inadequate treatments. Clinical and dermoscopic clues can be easily recognized, which help to prevent missing a melanoma. OBJECTIVES To study the clinical and dermoscopic findings in three cases of acral melanoma simulating warts that had been treated by dermatologists with curettage and cryotherapy. MATERIAL AND METHODS Clinical and dermoscopic study of the tumors and review of the most frequent simulators of acral melanoma reported in the literature. RESULTS In all three tumors, hyperkeratosis and the lack of specific pigmentation were observed. The parallel ridge pattern, revealed by dermoscopic examination, precipitated the recognition of acral melanoma. CONCLUSION In these cases that presented atypical characteristics of acral lesions, therefore challenging the diagnostic process, dermoscopic examination helped to confirm an accurate diagnosis of acral melanoma.

Fundamento Se considera que diversas lesiones cutaneas en la region lumbosacra son marcadores de riesgo de disrafia espinal oculta en el recien nacido. La resonancia magnetica (RM) espinal es la tecnica de eleccion para el diagnostico de disrafia espinal oculta. Objetivos Valorar si la ecografia espinal realizada antes de los 6 meses de edad en pacientes con marcadores cutaneos de disrafia es capaz de determinar la movilidad, el grosor y la altura del cono medular y describir estos hallazgos ultrasonograficos. Pacientes y metodo De enero de 2001 hasta octubre de 2004, se recogio de manera prospectiva, en 2 centros diferentes, los datos de 46 lactantes con algun marcador cutaneo de bajo riesgo de disrafia. En 42 se realizo una ecografia espinal antes de los 6 meses de edad, en 4 se realizo una RM porque tenian mas de 6 meses de edad y en 7 se realizo, ademas de la ecografia espinal, una RM. Resultados De los 46 lactantes, 43 (93,5%) presentaban una lesion congenita lumbosacra de bajo riesgo y 3 (6,5%), 2 o mas lesiones de este tipo. En todos los pacientes (42 de 42, el 100%) la ecografia espinal permitio medir y localizar la altura del cono medular, asi como su movilidad y grosor. En los 7 (100%) pacientes, en que ademas de la ecografia espinal se realizo una RM, se observaron los mismos resultados en ambas pruebas. Conclusiones La ecografia espinal realizada antes de los 6 meses de edad es una tecnica no invasiva y de bajo coste que permite determinar de forma precisa la movilidad, el grosor y la altura del cono medular y, por tanto, como minimo puede descartar una medula anclada en pacientes con marcadores cutaneos de bajo riesgo de disrafia espinal.

Introduccion Presentamos el caso de 2 pacientes con dermatomiositis (DM) que durante el curso de su enfermedad asociaron un cuadro de paniculitis. Casos clinicos La primera paciente es una mujer de 41 anos de edad, diagnosticada de DM y tratada con corticoids sistemicos, antimalaricos y azatioprina. A los 2 anos consulto por la aparicion de nodulos en los muslos y en las piernas. El estudio histologico mostro una paniculitis lobulillar y se inicio tratamiento sistemico con hidroxicloroquina, prednisona y corticoides topicos, sin obtener mejoria. Las lesiones cutaneas iniciaron su resolucion coincidiendo con la instauracion de tratamiento con inmunoglobulinas intravenosas (IGIV) y posteriormente ciclosporina. La segunda paciente es una mujer de 35 anos diagnosticada de DM refractaria al tratamiento con corticoides, antipaludicos y metotrexato. Un ano despues del diagnostico presento lesiones nodulares en las nalgas, los muslos, la cara interna de los brazos y el area submamaria, algunas de ellas con ulceracion. El estudio histologico mostro una paniculitis seudomembranosa. El tratamiento con IGIV y corticoterapia sistemica no consiguio la estabilizacion de las lesiones, por lo que se anadio ciclosporina oral. Discusion Aportamos 2 nuevos casos de DM asociados con paniculitis. El primero de ellos evoluciona de forma favorable, como la mayoria de los casos descritos en la bibliografia, en cambio la segunda paciente presenta una evolucion torpida complicada con ulceracion y refractaria a las diferentes terapias administradas. Las revisiones realizadas sugieren que la presencia de paniculitis en el contexto de DM puede suponer un signo de buen pronostico, con una respuesta positiva al tratamiento y una presencia minima de neoplasias asociadas.

Tradicionalmente, las decisiones clinicas se han basado en los resultados de eficacia de los ensayos clinicos. En la actualidad y de una forma creciente, los profesionales de la salud utilizan otras tecnicas, principalmente las evaluaciones economicas, para completar y mejorar el complicado proceso de toma de decisiones dentro del sistema sanitario. Por ese motivo y debido a que en distintas revisiones de estudios publicados1,2 se han demostrado carencias, tanto en la calidad de los trabajos realizados con estas tecnicas como en el estilo de sus informes, la capacidad de valorar la calidad de las evaluaciones farmacologicas desempena un papel cada vez mas importante en el amplio concepto del asesoramiento tecnologico sobre la salud. Por otro lado, el analisis de coste-efectividad es la tecnica de evaluacion mas utilizada en farmacoeconomia para la comparacion de distintas estrategias alternativas de intervencion terapeutica y se encuentran entre los criterios requeridos por el NICE (National Institute for Clinical Excellence) para recomendar un tratamiento. En este articulo se intenta proporcionar recomendaciones generales sobre la manera correcta de proceder, entender y obtener conclusiones de un analisis de costeefectividad (ACE) y, en la medida de lo posible, hacer extensivas dichas directrices a otros tipos de evaluacion farmacoeconomica, como los analisis de coste-utilidad (ACU) y los analisis de coste-beneficio (ACB).

Background: Leishmaniasis is a chronic protozoan disease in which organisms are found within phagolysosomes of the mononuclear phagocyte system. There are three major forms: cutaneous, mucocutaneous and visceral. We report the first case of visceral leishmaniasis with cutaneous involvement in a patient with rheumatoid arthritis treated with the anti-tumour necrosis factor (anti-TNF) adalimumab. Objective: To highlight cutaneous leishmaniasis as the first indicator of a kala-azar disease in a patient treated with anti-TNF and to review the literature on leishmaniasis in the context of anti-TNF therapy. Case Report: A 59-year-old woman presented with a crusted plaque on the right elbow 34 months after the initiation of adalimumab. A cutaneous biopsy showed intracellular amastigotes. No Leishmania parasites were observed in a bone marrow aspirate, but laboratory tests showed anaemia and impaired liver function, abdominal ultrasonography showed hepatomegaly, and ELISA serology was strongly positive for Leishmania antibodies in serum and urine. Adalimumab was withdrawn and treatment combining intralesional pentavalent antimonials and liposomal amphotericin was started. Eight weeks later, the leishmaniasis had resolved. Conclusion: A skin biopsy disclosing leishmaniasis should prompt tests to rule out visceral leishmaniasis, especially in an area such as the Mediterranean where the prevalence of latent Leishmania infection is high.

Case 1 A 3-month-old boy presented with two nodular lesions distributed symmetrically on the medial plantar surface of both heels, present since birth. The nodules were approximately 1 cm in diameter, pink in color, soft, mobile, and nonpainful to the touch (Fig. 1). The mother was a primigravida, with no previous medical history of interest or history of drug intake during pregnancy. The pregnancy passed without incident with normal delivery at term without complications, and the newborn was of appropriate weight for the gestational age. There was no family history of similar lesions. At 12 months of age, the lesions remained stable and asymptomatic. Figure 1. Bilateral nodular lesions on the medial internal plantar heel surface in a 3-month-old boy Download figure to PowerPoint Case 2 A 7-month-old girl presented with two symmetrical nodules of 1.2 cm in diameter located on the medial plantar surface of each heel, present since birth. The nodules were of a normal skin color, soft, mobile, and painless (Fig. 2). The mother was a secundigravida and the only medical history of note was hepatitis C virus infection 3 years earlier. The pregnancy progressed without incident with a normal delivery at term, and the newborn was of an appropriate weight for the gestational age. Significant in the family history was the presence of similar lesions in both the aunt and maternal grandfather; the mother herself denied having had similar lesions during childhood. In the case of the maternal aunt, the lesions had diminished in size to the point of completely disappearing at the age of 3 years. In the case of the maternal grandfather, the outcome was unknown. The lesions had reduced in size to approximately 1 cm in diameter in our patient at 12 months of age. Presently aged 12 months, she continues to be monitored periodically in our department; the lesions persist but no morphological changes or associated functional alterations have been observed. Figure 2. Bilateral nodular lesions on the medial internal plantar heel surface in a 7-month-old girl Download figure to PowerPoint

Scurvy is a set of clinical manifestations characterized by general weakness, anemia, gingivitis and cutaneous bleeding, caused by a lack of ascorbic acid in the diet. This pathology is currently a clinical rarity, although it can still be seen in cases of malnutrition associated with alcoholism or with dietary deficiencies, especially in childhood and old age. We present the case of a 45-year-old male who consulted his physician because of lower limb edema with follicular purpura, accompanied by asthenia, polyarthralgia and bleeding gums. After treatment with 1 g/day of vitamin C was initiated, the patient's symptoms quickly improved. The diagnosis of scurvy was based on the patient's clinical symptoms, dietary history and the rapid resolution of the symptoms when vitamin C supplements were initiated.

Iliopsoas impingement is an under recognized cause of failed total hip arthroplasty. We report 2 cases of iliopsoas impingement resolution diagnosed with the aid of imaging techniques and fluoroscopically guided injection.

The obturator internus muscle is an external rotator of the hip. Obturator internus injury may occur and be hidden by the piriformis syndrome. Clinical symptoms may offer some clues to the clinician. The selective injection technique described here facilitates precise diagnosis.

Pyoderma gangrenosum is a reactive inflammatory dermatosis which belongs to the spectrum of neutrophilic dermatoses. Due to a lack of diagnostic criteria, pyoderma gangrenosum is mainly a diagnosis of exclusion. It is rarely observed on the perineum, and vulvar involvement is even less frequent. Collagenous colitis is an idiopathic inflammatory colonic disease that is included in the microscopic colitides. The colonic mucosa and the crypt architecture are preserved but histologic alterations are found. We describe a case of collagenous colitis associated with vulvar pyoderma gangrenosum that improved spectacularly with cyclosporine 3 mg/kg/day and the twice-daily application of topical tacrolimus 0.1%.

Scurvy is a set of clinical manifestations characterized by general weakness, anemia, gingivitis and cutaneous bleeding, caused by a lack of ascorbic acid in the diet. This pathology is currently a clinical rarity, although it can still be seen in cases of malnutrition associated with alcoholism or with dietary deficiencies, especially in childhood and old age. We present the case of a 45-year-old male who consulted his physician because of lower limb edema with follicular purpura, accompanied by asthenia, polyarthralgia and bleeding gums. After treatment with 1 g/day of vitamin C was initiated, the patient's symptoms quickly improved. The diagnosis of scurvy was based on the patient's clinical symptoms, dietary history and the rapid resolution of the symptoms when vitamin C supplements were initiated.

The diagnosis of common carpal tunnel syndrome, usually relies only on clinical grounds and electromyographic study. We present a 60-year-old woman who was diagnosed with systemic primary AL amyloidosis many years after the carpal tunnel syndrome had begun.

A 45-year-old woman developed a severe eczematous reaction localized on the application site after using a clarifying cream. Patch testing showed positively to vitamin K1.

Pegylated interferon alfa-2b is a formulation of recombinant human interferon conjugated with polyethylene glycol. Compared with standard interferon alfa injections, this preparation has a longer half-life allowing for once-weekly injections and superior antiviral efficacy in the treatment of hepatitis C when used in combination with ribavirin. Cutaneous side effects caused by interferon are well known. Cutaneous necrosis as a result of interferon alfa is an infrequent complication with unknown pathogenesis, in which a cutaneous local immune-mediated inflammatory process might be involved. We report 5 patients (3 patients with chronic hepatitis C treated with pegylated interferon alfa-2b in association with oral ribavirin and two patients with chronic myelocytic leukemia) who developed local cutaneous reactions at sites of injection after the administration of weekly subcutaneous injections of pegylated interferon alfa-2b at different doses. The ulcers slowly healed with local therapy, but two patients required dose modification of the pegylated interferon alfa-2b and one patient required treatment withdrawal. We review the literature on previously reported cases of cutaneous necrosis after injection of standard interferon alfa or pegylated interferon alfa-2b and discuss the different pathophysiologic mechanisms that might be involved.

We describe the clinical and histopathological results of plaque psoriasis in eleven adult patients with knee osteoarthritis and long-standing, moderate to severe psoriasis resistant to conventional therapy treated with chondroitin sulfate. Patients received 800 mg per day of chondroitin sulfate for 2 months. Skin biopsies were obtained before and after treatment. All patients but one presented a dramatic improvement of the condition of the skin, with a reduction of swelling, redness, flaking, and itching (clearance of psoriasis in one patient), increase in the hydration and softening of the skin, and amelioration of scaling. Histopathologically, there was a statistically significant decrease in epidermal thickness, a decrease in the thickness between the stratum basale and the stratum granulosum, a significant improvement of the degree of psoriasis activity, and a decrease in the number of keratinocytes stained with Ki-67. The confirmation of these serendipitous findings in controlled prospective studies could represent an important advance in the therapeutic armamentarium for patients with psoriasis given the excellent safety profile of chondroitin sulfate.