Advances in treatment for lipoid proteinosis (Urbach-Wiethe disease): a case report and systematic review.

BACKGROUND: Lipoid proteinosis (LP), also known as Urbach-Wiethe disease, is a rare autosomal recessive genodermatosis, caused by mutations in the ECM1 gene. This results in the deposition of periodic acid-Schiff (PAS)-positive, hyaline-like material on the skin, mucosae and internal organs. OBJECTIVES: To present a case report of LP and a systematic review to synthesize the scientific literature on the management of this uncommon and frequently missed diagnosis. METHODS: We present a case report of a 48-year-old man with LP who exhibited significant improvement after oral acitretin therapy. To address the lack of large case-control studies on LP treatment, we performed a systematic review of the literature following the PRISMA 2020 criteria. The search was conducted in PubMed, Web of Science, Cochrane and Scopus databases from inception until June 2023. To assess the methodological quality of case reports and case series, we used the Joanna Briggs Collaboration critical appraisal tool. RESULTS: We included 25 studies that met eligibility criteria. Data from 44 patients with a histopathologically confirmed diagnosis were analysed. Treatment ranged from systemic therapies (acitretin, etretinate, dimethyl sulfoxide, corticosteroids, penicillamine) to surgical or laser procedures. Regarding methodological quality, the main discrepancies arose in the reporting of participant characteristics and treatment interventions. CONCLUSIONS: Low-dose oral acitretin could have potential in managing LP, exhibiting fewer side-effects compared with other therapeutic agents. Further research is needed to establish more comprehensive and evidence-based treatment guidelines.

Physicochemical and ecotoxicological approaches for Moknine Continental Sebkha in Tunisia.

Degradation of water quality is an emerging issue in many developing countries. In this context, industrial and domestic effluents heavily contaminate the coast of Moknine Continental Sebkha in Tunisia. The present study aimed to biomonitor the seawater quality of the Moknine Continental Sebkha coast using physicochemical and ecotoxicological approaches. The ecotoxicological assessment was performed using three species representing different trophic levels, namely Vibrio fischeri, Selenastrum capricornutum, and Lepidium sativum. In the physicochemical analysis such as BOD (biochemical oxygen demand), COD (chemical oxygen demand), TSS (total suspended solids), TOC (total organic carbon), NO3- (nitrate), AOX (adsorbable organic halogen), the recorded levels of pH and total suspended solids did not comply with the Tunisian standard (NT.09.11/1983). The ecotoxicological data confirmed that the tested water samples displayed toxicity to two test indicators L. sativum and S. capricornutum. A targeted chemical screening of the Moknine Continental Sebkha coast previously performed revealed the presence of total mercury, four phthalate acid esters, and one non-phthalate plasticizer, a fact that could explain the observed ecotoxicological effects and therefore might harm the biotic area and the health of the surrounding population.

Dupilumab significantly improves sleep in adults with atopic dermatitis: results from the 12-week placebo-controlled period of the 24-week phase IV randomized double-blinded placebo-controlled DUPISTAD study.

BACKGROUND: Sleep disturbance is a prominent symptom of atopic dermatitis (AD) and can result in insomnia, daytime fatigue, drowsiness, reduced productivity and impaired quality of life (QoL). OBJECTIVES: The Dupilumab Effect on Sleep in AD Patients (DUPISTAD) phase IV randomized double-blinded placebo-controlled study evaluated the impact of dupilumab treatment on sleep and other patient- and physician-reported outcomes. METHODS: Adults with moderate-to-severe AD were randomized 2 : 1 to dupilumab 300 mg once every 2 weeks (q2w) or placebo for 12 weeks; concomitant topical corticosteroids were permitted. Patients subsequently entered an open-label phase and received dupilumab 300 mg q2w for a further 12 weeks. The primary endpoint was the percentage change in sleep quality from baseline to week 12, assessed using a novel numeric rating scale (NRS). Secondary and exploratory endpoints included percentage change in peak pruritus NRS (PP NRS), change in SCORing Atopic Dermatitis (SCORAD), SCORAD sleep visual analogue scale (VAS), Eczema Area and Severity Index, Patient-Reported Outcomes Measurement Information System (PROMIS) sleep-related impairment T-score and the Epworth Sleepiness Scale. Sleep diary and wrist actigraphy measurements were recorded throughout the study. RESULTS: In total, 127 patients received dupilumab and 61 patients received placebo. Demographic and baseline disease characteristics were balanced between groups. Sleep quality NRS significantly improved in patients treated with dupilumab by week 12 vs. placebo [least squares mean of the difference (LSMD) -15.5%, P < 0.001]. PP NRS (LSMD -27.9%, P < 0.001), SCORAD (LSMD -15.1, P < 0.001), SCORAD sleep VAS (LSMD -2.1, P < 0.001) and PROMIS T-score (LSMD -3.6, P < 0.001) were also significantly improved at week 12 with dupilumab vs. placebo. The overall percentage of patients reporting treatment-emergent adverse events was lower in the dupilumab group (56.7%) than in the placebo group (67.2%). CONCLUSIONS: Dupilumab significantly improved sleep quality and perception of sleep continuity, itch, metrics of AD severity and QoL in adults with moderate-to-severe AD, with an acceptable safety profile compared with placebo.

Clustering of systemic lupus erythematosus mortality in southwestern Spain.

OBJECTIVE: To analyse time trends in systemic lupus erythematosus (SLE) mortality and explore possible provincial clustering of SLE mortality in Spain (2001-2020). METHODS: We conducted an ecological study using deaths registered in SLE at the Spanish National Institute of Statistics between 2001 and 2020. Jointpoint regression models have been used to evaluate temporal trends. To analyse the spatial pattern of SLE mortality in men and women in Spain, crude rates, age-standardised mortality rates (ASMRs), smooth relative risk (RR) and posterior probabilities (PP) for RR greater than one for the period 2001-2020 were calculated. The Global Moran I index was used to assess the existence of global spatial autocorrelation. Local indicators of spatial association (LISA) and Kulldorff's spatial scan statistic were used to identify clusters. RESULTS: Over the 20 years analyzed in this study, the SLE average ASMR for the period was 2.7 for women and 0.7 for men, with a sex ratio (female/male) of 3.8. In men, no province showed a RR>1. Conversely, in women, eight provinces showed values of RR> 1 with a PP greater than 0.8 (Seville, Cadiz, Huelva and Murcia in the south, Barcelona, Zaragoza, Huesca and Leon in the north). In men, neither of the two methods detected a clustering of provinces. However, in women, both methods identified a cluster of provinces located in the southwest of the country (Huelva, Cádiz, Seville and Malaga) as a cluster with significant excess mortality. In the second cluster (centred on the province of Huelva) obtained with the Kulldorff method, two more provinces were added (Badajoz and Cordoba, also located in the southwest). CONCLUSIONS: We detected a cluster of provinces with an excess risk of female SLE mortality in the southwest of Spain.

Prediction of melanoma Breslow thickness using deep transfer learning algorithms.

BACKGROUND: The distinction between in situ melanoma (MIS) and invasive melanoma is challenging even for expert dermatologists. The use of pretrained convolutional neural networks (CNNs) as ancillary decision systems needs further research. AIM: To develop, validate and compare three deep transfer learning (DTL) algorithms to predict MIS vs. invasive melanoma and melanoma with a Breslow thickness (BT) of < 0.8 mm vs. ≥ 0.8 mm. METHODS: A dataset of 1315 dermoscopic images of histopathologically confirmed melanomas was created from Virgen del Rocio University Hospital and open repositories of the International Skin Imaging Collaboration archive and Polesie S et al. (Dermatol Pract Concept 2021; 11:e2021079). The images were labelled as MIS or invasive melanoma and < 0.8 mm or ≥ 0.8 mm of BT. We conducted three trainings, and overall means for receiver operating characteristic (ROC) curves, sensitivity, specificity, positive and negative predictive value, and balanced diagnostic accuracy outcomes were evaluated on the test set with ResNetV2, EfficientNetB6 and InceptionV3. The results of 10 dermatologists were compared with the algorithms. Grad-CAM gradient maps were generated, highlighting relevant areas considered by the CNNs within the images. RESULTS: EfficientNetB6 achieved the highest diagnostic accuracy for the comparison between MIS vs. invasive melanoma (61%) and BT < 0.8 mm vs. ≥ 0.8 mm (75%). For the BT comparison, ResNetV2 with an area under the ROC curve of 0.76 and InceptionV3 with an area under the ROC curve of 0.75, outperformed the results obtained by the dermatologist group with an area under the ROC curve of 0.70. CONCLUSION: EfficientNetB6 recorded the best prediction results, outperforming the dermatologists for the comparison of 0.8 mm of BT. DTL could be an ancillary aid to support dermatologists' decisions in the near future.

Treatment of severe atopic dermatitis with tralokinumab in clinical practice: short-term effectiveness and safety results.

BACKGROUND: Tralokinumab was recently approved for the treatment of moderate-to-severe atopic dermatitis (AD) and is the first selective interleukin (IL)-13 inhibitor that specifically neutralizes IL-13 with high affinity. OBJECTIVES: To determine the real-life short-term effectiveness and safety of tralokinumab treatment in patients with moderate-to-severe AD. METHODS: A multicentre retrospective study was conducted including adult patients with moderate-to-severe AD who started tralokinumab treatment from 1 April to 30 June 2022 in 16 Spanish hospitals. Demographic and disease characteristics, severity and quality of life scales were collected at the baseline visit and at weeks 4 and 16. RESULTS: Eighty-five patients were included. Twenty-seven patients (32%) were non-naive to advanced therapy (biological or Janus kinase inhibitors inhibitors). All included patients had severe disease with baseline Eczema Area and Severity Index (EASI) scores of 25.4 (SD 8.1), Dermatology Life Quality Index (DLQI) 15.8 (5.4) and peak pruritus numerical rating scale (PP-NRS) 8.1 (1.8) and 65% had an Investigator's Global Assessment (IGA) of 4. At week 16, there was improvement on all scales. The mean EASI decreased to 7.5 (SD 6.9, 70% improvement), SCORing Atopic Dermatitis improved 64% and PP-NRS, 57%. Also, 82%, 58% and 21% of the patients achieved EASI 50, 75 and 90, respectively. The percentage of EASI 75 responders was significantly higher among the naive vs. non-naive groups (67% vs. 41%). The safety profile was acceptable. CONCLUSIONS: Patients, with a long history of disease and prior multidrug failure, showed a good response to tralokinumab, confirming clinical trial results.

Systemic sclerosis mortality trends in Spain from 1980 to 2019: age-period-cohort and joinpoint analysis.

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune chronic rheumatic disease with a high mortality rate, which continues to be a challenge for clinicians today. AIM: To assess changes in mortality trends in the Spanish SSc population between 1980 and 2019, taking into account the independent effects of sex, age, time period and birth cohort. METHODS: SSc death records and mid-year population data were collected from the National Statistics Institute. Age-standardized mortality rates were calculated for the overall population and for each sex (male, female) and age group (5-year groups). Significant changes in mortality trends were identified by joinpoint regressions. An age-period-cohort (APC) analysis and potential years of life lost (PYLL) analysis were performed to identify the burden of SSc. RESULTS: Age-standardized mortality rates due to SSc increased from 1.87 (95% CI 1.00-3.02) per 1 000 000 inhabitants between 1980 and 1984, to 2.47 (95% CI 1.74-3.02) per 1 000 000 inhabitants between 2015 and 2019. The relative risk of mortality fell in all groups in cohorts born after 1990. The PYLL rates showed a gradual rise for both sexes. CONCLUSION: There was an increase in overall SSc mortality in Spain during the 39 years evaluated, although there was a progressive drop for men.

Trends in mortality rates for oral and oropharyngeal cancer in Spain, 1979-2018.

OBJECTIVE: To analyse mortality rate trends in Spain for oral cavity and oropharyngeal cancer (OCOPC) from 1979 to 2018, evaluating differences between oral cavity cancer (OCC) and oropharyngeal cancer (OPC). MATERIALS AND METHODS: Death certificates and mid-year population data were collected from the Spanish National Statistics Institute. Age-standardized mortality rates were calculated using the direct method. Joinpoint regressions were used to identify significant changes in mortality trends. Independent effects of age, period and cohort (APC) were estimated. RESULTS: A total of 52,057 deaths were registered from OCOPC, 38,988 from OCC and 13,069 from OPC between 1979 and 2018. While OCC mortality rates declined, OCOPC rates increased slightly and OPC significantly. OCC and OPC mortality reached their highest values between 1979 and 1992, when OCC rates began to decrease in males and OPC levelled off until 2018. Lip cancer suffered the highest drop. APC models showed a mortality increase in males and females from 40 to 45 and 50 to 55 years of age, respectively. CONCLUSIONS: Favourable OCC mortality trends was plausibly influenced by decreased tobacco/alcohol consumption, while OPC rise was probably associated with increased human papillomavirus infection. The importance of closely monitoring these cancers by age group, sex and location, and continuing with preventive measures against known risk factors, is highlighted.

Dropout Rate in Digital Health Interventions for the Prevention of Skin Cancer: Systematic Review, Meta-analysis, and Metaregression.

BACKGROUND: Digital strategies are innovative approaches to the prevention of skin cancer, but the attrition following this kind of intervention needs to be analyzed. OBJECTIVE: The aim of this paper is to assess the dropouts from studies focused on digital strategies for the prevention of skin cancer. METHODS: We conducted this systematic review with meta-analyses and metaregression according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statements. Search terms for skin cancer, digital strategies, and prevention were combined to search PubMed, Scopus, Web of Science, CINAHL, and Cochrane Library from inception until July 2022. Randomized clinical trials that reported dropouts of participants and compared digital strategies with other interventions to prevent skin cancer in healthy or disease-free participants were included. Two independent reviewers extracted data for analysis. The Revised Cochrane Collaboration Bias tool was employed. We calculated the pooled dropout rate of participants through a meta-analysis of proportions and examined whether dropout was more or less frequent in digital interventions against comparators via an odds ratio (OR) meta-analysis. Data were pooled using a random-effects model. Subgroup meta-analyses were conducted in a meta-analysis of proportions and OR meta-analysis to assess the dropout events when data were sorted by digital interventions or control comparator. A univariate metaregression based on a random-effects model assessed possible moderators of dropout. Participants' dropout rates as pooled proportions were calculated for all groups combined, and the digital and comparator groups separately. OR>1 indicated higher dropouts for digital-based interventions. Metaregressions were performed for age, sex, length of intervention, and sample size. RESULTS: A total of 17 studies were included. The overall pooled dropout rate was 9.5% (95% CI 5.0-17.5). The subgroup meta-analysis of proportions revealed a dropout rate of 11.6% for digital strategies (95% CI 6.8-19.0) and 10.0% for comparators (95% CI 5.5-17.7). A trend of higher dropout rates for digital strategies was observed in the overall (OR 1.16, 95% CI 0.98-1.36) and subgroup OR meta-analysis, but no significant differences were found between the groups. None of the covariates moderated the effect size in the univariate metaregression. CONCLUSIONS: Digital strategies had a higher dropout rate compared to other prevention interventions, but the difference was not significant. Standardization is needed regarding reporting the number of and reasons for dropouts. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) CRD42022329669; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=329669.

Hidradenitis suppurativa and Down syndrome in a single-centre sample: A cross-sectional study.

Down syndrome (DS) has been related to a higher risk of hidradenitis suppurativa (HS). This cross-sectional study assessed DS patients with HS in a Spanish single-centre sample. DS participants presented a lower age of onset, age at diagnosis and time to diagnosis. Also, DS was not associated with the severity of HS measured by baseline IHS4 .

Estimated projection of oral cavity and oropharyngeal cancer deaths in Spain to 2044.

BACKGROUND: Oral cavity cancer (OCC) and oropharyngeal cancer (OPC) are two common malignancies whose mortality is worryingly increasing worldwide. However, few studies have estimated the mortality trends for these cancers in the coming years. This study analysed the mortality rates for OCC and OPC observed between 1980 and 2019 to generate a predictive model for the next 25 years in Spain. METHODS: Mid-year population data and death certificates for the period 1980-2019 were obtained from the Spanish National Institute of Statistics. The Nordpred program (Norwegian Cancer Registry, Oslo, Norway) was used to calculate adjusted mortality rates as well as estimated mortality projections with an age-period-cohort model for the period 2020-2044. RESULTS: The specific mortality rate per 100,000 inhabitants for OCC decreased from 2.36 (1980-1984) to 2.17 (2015-2019) and is expected to decline to 1.68 (2040-2044), particularly in males. For OPC, mortality rates rose from 0.67 (1980-1984) to 1.23 (2015-2019) and are projected to drop to 0.71 (2040-2044). In the group of females > 65 years predictions showed rising mortality rates for both OCC and OPC. The predictive model projects more deaths in females than in males for OCC in the period 2040-2044, while deaths for OPC will decrease in males and gradually increase in females. CONCLUSIONS: Although OCC mortality rates have been found to decrease in males in the last observed decades, there is still room to improve them in females > 65 years in the future by promoting campaigns against smoking and alcohol consumption. OPC mortality will become a growing health problem. Vaccination campaigns for the prevention of human papillomavirus-associated cancers may have a long-term impact on the mortality of these cancers, which should be evaluated in upcoming studies. CLINICAL RELEVANCE: Our findings highlighted the importance of closely monitoring OCC and OPC mortality rates in the coming years by age group and sex, and the need to continue preventive measures against the main known risk factors, such as tobacco, alcohol, and human papillomavirus infection.

Cutaneous malignant melanoma mortality in Andalusia from 1979 to 2018. Toward new perspectives?

Malignant melanoma accounts for 80% of deaths due to skin cancer. Its incidence is globally increasing. However, melanoma mortality seems to be decreasing. The aim of this study was to analyze mortality rates due to melanoma in Andalusia between 1979 and 2018. Deaths due to melanoma and mid-year population in Andalusia were collected from the National Institute of Statistics. Age-adjusted mortality rates were calculated for overall population and for each sex and age group. Regression models were used to calculate significant points of change. Sex ratio and the independent effects of age, period, and cohort were also analyzed. Age-adjusted mortality due to melanoma rose from 0.61 to 1.94 deaths per 100.000 from 1979 to 2018 for the overall population. A significant change of trends was detected around 1994 when, after a steady rise from 1979, mortality rates stabilized up to the end of the period studied. The cited increase was more pronounced in >64 year males. From the end of the 2000s, there was a decrease in mortality rates to date in all population groups, producing a period effect. A stabilization in melanoma mortality rates was observed in Andalusia from 1994 with a decrease in some groups at the beginning of the 21st century. Trends observed in Andalusia do not differ substantially from those in Spain. The development of new therapies and an earlier diagnosis may have an influence in those changes. Studies that compare differences between Spanish regions are needed to define better prevention strategies.

Direct-to-consumer, store-and-forward teledermatology with dermoscopy using the pharmacist as patient point-of-contact.

OBJECTIVE(S): To evaluate the frequency of nonmelanoma skin cancer (NMSC), NMSC precursors, and melanoma on a store-and-forward dermatology model featuring the pharmacist as the patient's point-of-contact. The secondary objective was to define lesion changes and symptoms perceived by patients (clinical prediction rules by nonexpert observers) that can be predictive of malignity. METHODS: A cross-sectional study of teledermatology consultation was performed. All patients who underwent a teledermatology consultation between September 2018 and March 2020 were included. A patient could have more than 1 lesion per consultation. The object of the study was a defined dermatologic lesion. The differences between the variables were analyzed using a univariate model based on the chi-square test for independent qualitative variables and Fisher exact test in cases when the expected values in any of the cells of a contingency table were less than 5. Statistical significance was set at P < 0.05 (2-tailed). RESULTS: A total of 225 lesions in 218 patients were considered for this study; 53.8% (n = 121) of the lesions were classified as benign, 16.4% (n = 37) as dubious, 23.1% (n = 52) as NMSC precursors, 5.8% (n = 13) as NMSC, and 0.9% (n = 2) as melanomas. Of the reported clinical lesion changes, spontaneous pain, pruritus, surface texture changes, color changes, or form changes had no statistically significant relationship with the diagnostic group, whereas the presence of spontaneous bleeding (P = 0.015) and size changes (P = 0.026) were more frequently observed in the "dubious lesion" and "of oncological relevance lesion" groups. CONCLUSION: This "direct-to-consumer," store-and-forward teledermatology with dermoscopy model featuring the pharmacist as the patient's point-of-contact is useful for the diagnosis of melanoma, NMSC, and NMSC precursors when backed by a robust dermatology service.

Trends in mortality from lupus in Spain from 1980 to 2018.

BACKGROUND: Recent studies suggest that Systemic lupus erythematosus (SLE) mortality rates in Spain are decreasing. However, SLE mortality in Spain has been poorly studied. The purpose of study is to assess the temporal trends of mortality rates in the Spanish population with SLE from 1980 to 2018. METHODS: Death records and mid-year population data were collected from the National Statistics Institute. Age-standardized mortality rates were calculated for overall population and for each sex and age group. Significant changes in mortality trends were identified by Joinpoint regressions. Also, an Age-period-cohort (APC) and Potential Years of Life Lost (PYLL) analysis was carried out to know the burden of SLE disease. RESULTS: The overall SLE mortality rates in Spain has experimented an increased through the last 39 years. Mortality rates from the period 1980-1984 was 0.83 per 1.000.000 inhabitants, reaching the value to 1.77 cases per 1.000.000 from the period 2014-2018. A decreasing trend has been observed since 1999. CONCLUSIONS: SLE mortality rate has increased in Spain between 1980 and 1999, with a sustained decrease up to our days.

Cytostatic compounds in sludge and sediment: extraction and determination by a combination of microwave-assisted extraction and UHPLC-MS/MS.

Cytostatic compounds are an important group of micro-pollutants since they are used to kill cells or stop cell division. For this reason, they are also considered mutagenic. Several cytostatic compounds have been detected in hospital effluents, in the influents and effluents of wastewater treatment plants and even in river water. However, their detection in solid matrices is very scarce. In this work, we have developed a new procedure based on microwave-assisted extraction (MAE) for the extraction of cytostatic compounds from sludge and sediment before determination by ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). To develop this procedure, we have chosen a group of eight widely used cytostatic compounds and carried out a systematic experimental design to optimize the extraction conditions. Under these optimal conditions, the studied cytostatic compounds are extracted with good sensitivity, with recoveries ranging from 65 to 122% in sludge and recoveries varying between 49 and 109% in sediment, with the exception of etoposide, which has a lower recovery from these types of samples. The limits of detection were from 0.42 to 79.8 ng g-1 in sludge and from 0.10 to 87.5 ng g-1 in sediment. Intraday and interday relative standard deviations (RSDs) were below 15% and 18%, respectively, in both matrices at the tested concentrations. The total procedure was applied to samples of sludge taken from the main wastewater treatment plant (WWTP) of the island of Gran Canaria (Spain) and for sediment samples obtained close to the marine outfalls of different wastewater treatment plants for the same island. Graphical abstract.

Prevalence of chronic urticaria refractory to antihistamines in Andalucia, Spain.

Chronic urticaria (CU) has a devastating effect on the quality of life of patients who suffer from it. The objective of this study is to determine the prevalence of severe chronic spontaneous urticaria (CSU) in adults in eight health areas in Andalucía. A retrospective observational study from January 2019 to December 2019 was conducted with the participation of seven reference hospitals that were analyzed, including a total reference population of 3 159 001 individuals ≥18 years. The analysis was carried out on the characteristics of the population and the estimated prevalence. In total, 369 patients with a diagnosis of CSU refractory to antagonist of histamine were registered. We have found a prevalence of refractory patients of 0.0012% (95% CI 0.0010%-0.0013), ranging from 0.006% to 0.02%. The present study has helped to describe the prevalence and characteristics of patients with severe urticarial. The prevalence is lower than previously reported. We have observed differences between hospital areas. There will be a new line of research at the national level to help improve the identification of patients with CSU.

Determination of 5-fluorocytosine, 5-fluorouracil, and 5-fluorouridine in hospital wastewater by liquid chromatography-mass spectrometry.

Chemotherapeutics are pharmaceutical compounds the occurrence of which in the environment is of growing concern because of the increase in treatments against cancer diseases. They can reach the aquatic ecosystems after passing through wastewater treatment plants without complete removal. One of the most frequently used chemotherapeutics is 5-fluorouracil which exhibits a strong cytostatic effect. In this paper, an analytical methodology was developed, validated, and applied to determine 5-fluorouracil, its precursor, 5-fluorocytosine, and its major active metabolite, 5-fluorouridine, in hospital wastewater samples. Due to the expected low concentrations after dilution and interferences present in such a complex matrix, a very selective and sensitive detection method is required. Moreover, an extraction method must be implemented prior to the determination in order to purify the sample extract and preconcentrate the target analytes at micrograms per liter concentration levels. Solid-phase extraction followed by liquid chromatography with tandem mass spectrometry was the combination of choice and all included parameters were studied. Under optimized conditions for wastewater samples analysis, recoveries from 63 to 108% were obtained, while intraday and interday relative standard deviations never exceeded 20 and 25%, respectively. Limits of detection between 61 and 620 ng/L were achieved. Finally, the optimized method was applied to samples from hospital wastewater effluents.

Occurrence of benzotriazole UV stabilizers in coastal fishes.

Chemicals added in personal care products are of emerging concern because their fate and their effect on the environment is not completely known. Benzotriazole UV stabilizers (BUVSs) are compounds used in different cosmetic products, which may reach the marine environment through marine discharge from treated waters or directly from bathing areas. Once released into the aquatic ecosystem, BUVSs can be bioaccumulated by aquatic organisms. To identify the human exposure risk, it is important to have suitable analytical methods to determine the presence of BUVSs in these organisms. Because of the complexity of such a biological matrix, selective extraction and detection techniques are required to isolate and quantify these kinds of pollutants at trace levels. In the present work, we optimized a method based on microwave-assisted extraction combined with ultra-high performance liquid chromatography and mass spectrometry detection to determine six benzotriazole compounds in fish samples. The absolute extraction yields provided by the proposed method were higher than 40% for most compounds, with intra-day and inter-day relative standard deviations ranging from 0.27 to 6.06 and 1.12-21.3%, respectively. The limits of quantification were in the range of 1.13-9.66 ng g-1 (dry weight). The method was applied to the study of three species of fish (Boops boops, Sphyraena viridensis, Sphoeroides marmoratus) that were collected close to three marine outfalls of treated waters on the Gran Canaria Island (Spain) for two years. Four of the six studied compounds, UV-326, UV-328, UV-329 and UV-360, were found with concentrations ranging from 1.34 ng g-1 to 45.6 ng g-1 (dry weight).

Fifty-two week follow-up safety and effectiveness results of dupilumab treatment of moderate-to-severe atopic dermatitis from a retrospective, multicentric series.

Atopic dermatitis (AD) is a chronic, systemic disease that has a multifactorial etiology, where immune system disorders and epidermal barrier dysfunction are added to the influence of genetic and environmental factors. Dupilumab has been approved by United States and the European Union regulatory agencies in 2017 for the treatment of moderate-to-severe AD in adult patients who are candidates for systemic treatment. In this short report, we present a retrospective, multicentric study, in which five hospitals in Andalusia, Spain, have taken part. Our objective is to evaluate the safety and effectiveness of dupilumab in patients with moderate-to-severe AD treated with dupilumab with at least 52 weeks of follow-up.

Monitoring and environmental risk assessment of benzotriazole UV stabilizers in the sewage and coastal environment of Gran Canaria (Canary Islands, Spain).

Benzotriazole UV stabilizers (BUVSs) are emerging contaminants that are widely used in personal care products, such as cosmetics and sunscreens, to absorb ultraviolet light. These compounds have been described as bioaccumulative, pseudo-persistent and toxic; therefore, it is of great importance to investigate them and determine their presence and distribution in the environment. In this research, we performed a two-year monitoring study to identify six BUVS compounds (UV-P, UV-326, UV-327, UV-328, UV-329 and UV-360) in different environmental compartments from Gran Canaria (Canary Islands, Spain): influent and effluent from five wastewater treatment plants (WWTPs) and seawater and sediment samples from three marine areas influenced by sewage outfalls discharges from WWTPs. Two methods based on on-line solid-phase extraction and microwave-assisted extraction coupled with ultra-high-performance liquid chromatography with mass spectrometry detection were applied to quantify the analytes in liquid and solid samples, respectively. The target BUVSs were measured in sewage, coastal seawater and sediment samples in concentrations in the ranges of 13.12-1933 ng L-1, 67.01-2419 ng L-1 and 4.42-2162 ng kg-1 dry weight, respectively. The studied compounds exhibited different trends of occurrence in aqueous and solid samples due to their different coefficients of hydrophobicity. The majority of the positive samples belonged to the most touristic sampling location of the island. The estimated hazard quotient, HQ, revealed no risk from the target compounds at the measured concentrations levels.