Mohs micrographic surgery in immunosuppressed vs immunocompetent patients: Results of a prospective nationwide cohort study (REGESMOHS, Spanish registry of Mohs surgery).

BACKGROUND: Immunosuppressed (IS) patients, particularly solid organ transplant recipients and those on immunosuppressive therapy, face a higher incidence and recurrence of nonmelanoma skin cancers (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Mohs micrographic surgery (MMS) is the preferred treatment for high-risk NMSC due to its high cure rate and margin examination capabilities. However, IS patients may experience more complications, such as surgical site infections, and a greater risk of recurrence, making their outcomes a subject of interest. OBJECTIVES: This study aimed to compare IS and immunocompetent (IC) patients undergoing MMS for NMSC in terms of baseline characteristics, intra- and post-surgical complications, and postoperative recurrence rates. METHODS: The study utilized data from the REGESMOHS registry, a 7-year prospective cohort study in Spain. It included 5226 patients, categorizing them into IC (5069) and IS (157) groups. IS patients included solid organ transplant recipients, those on immunosuppressive treatments, individuals with haematological tumours and HIV-positive patients. Patient data, tumour characteristics, surgical details and outcomes were collected and analysed. RESULTS: IS patients demonstrated a higher proportion of SCC, multiple synchronous tumours and tumours invading deeper structures. Complex closures, unfinished MMS and more surgical sections were observed in the IS group. Although intra-operative morbidity was higher among IS patients, this difference became non-significant when adjusted for other variables such as year of surgery, antiplatelet/anticoagulant treatment or type of closure. Importantly, IS patients had a substantially higher recurrence rate (IRR 2.79) compared to IC patients. CONCLUSIONS: This study suggests that IS patients may be at a higher risk of development of AE such as bleeding or tumour necrosis and are at a higher risk of tumour recurrence. Close follow-up and consideration of the specific characteristics of NMSC in IS patients are crucial. Further research with extended follow-up is needed to better understand the long-term outcomes for this patient group.

Development and validation of a model to predict complex Mohs micrographic surgery in clinical practice: REGESMOSH scale.

INTRODUCTION: There is still a need to develop a simple algorithm to identify patients likely to need complex Mohs micrographic surgery (MMS) and optimize MMS schedule. The main objectives of this study are to identify factors associated with a complex MMS and develop a predictor model of the number of stages needed in surgery and the need for a complex closure. MATERIALS AND METHODS: A nationwide prospective cohort study (REGESMOHS, the Spanish Mohs surgery registry) was conducted including all patients with a histological diagnosis of basal cell carcinoma (BCC). Factors related to three or more stages and a complex closure (that needing a flap and/or a graft) were explored and predictive models were constructed and validated to construct the REGESMOSH scale. RESULTS: A total of 5226 patients that underwent MMS were included in the REGESMOHS registry, with 4402 (84%) having a histological diagnosis of BCC. A total of 3689 (88.9%) surgeries only needed one or two stages and 460 (11.1%) required three or more stages. A model to predict the need for three or more stages included tumour dimension, immunosuppression, recurrence, location in risk areas, histological aggressiveness and previous surgery. Regarding the closure type, 1616 (38.8%) surgeries were closed using a non-complex closure technique and 2552 (61.2%) needed a complex closure. A model to predict the need for a complex closure included histological aggressiveness, evolution time, patient age, maximum tumour dimension and location. CONCLUSION: We present a model to predict MMS needing ≥3 stages and a complex closure based on epidemiological and clinical data validated in a large population (with real practice variability) including different centres that could be easily implemented in clinical practice. This model could be used to optimize surgery schedule and properly inform patients about the surgery duration.

Development and validation of a Spanish-language spatial release from masking task in a Mexican population.

This study validates a new Spanish-language version of the Coordinate Response Measure (CRM) corpus using a well-established measure of spatial release from masking (SRM). Participants were 96 Spanish-speaking young adults without hearing complaints in Mexico City. To present the Spanish-language SRM test, we created new recordings of the CRM with Spanish-language Translations and updated the freely available app (PART; https://ucrbraingamecenter.github.io/PART_Utilities/) to present materials in Spanish. In addition to SRM, we collected baseline data on a battery of non-speech auditory assessments, including detection of frequency modulations, temporal gaps, and modulated broadband noise in the temporal, spectral, and spectrotemporal domains. Data demonstrate that the newly developed speech and non-speech tasks show similar reliability to an earlier report in English-speaking populations. This study demonstrates an approach by which auditory assessment for clinical and basic research can be extended to Spanish-speaking populations for whom testing platforms are not currently available.

Molecular epidemiology of paediatric invasive pneumococcal disease in Andalusia, Spain.

This study aimed to assess the impact of the introduction of pneumococcal conjugate vaccine 13 (PCV13) on the molecular epidemiology of invasive pneumococcal disease (IPD) in children from Andalusia. A population-based prospective surveillance study was conducted on IPD in children aged <14 years from Andalusia (2018-2020). Pneumococcal invasive isolates collected between 2006 and 2009 in the two largest tertiary hospitals in Andalusia were used as pre-PCV13 controls for comparison of serotype/genotype distribution. Overall IPD incidence rate was 3.55 cases per 100 000 in 2018; increased non-significantly to 4.20 cases per 100 000 in 2019 and declined in 2020 to 1.69 cases per 100 000 (incidence rate ratio 2020 vs. 2019: 0.40, 95% confidence interval (CI) 0.20-0.89, P = 0.01). Proportion of IPD cases due to PCV13 serotypes in 2018-2020 was 28% (P = 0.0001 for comparison with 2006-2009). Serotypes 24F (15%) and 11A (8.3%) were the most frequently identified non-PCV13 serotypes (NVT) in 2018-2020. Penicillin- and/or ampicillin-resistant clones mostly belonged to clonal complex 156 (serotype 14-ST156 and ST2944 and serotype 11A-ST6521). The proportion of IPD cases caused by PCV13 serotypes declined significantly after the initiation of the PCV13 vaccination programme in 2016. Certain NVT, such as serotypes 24F and 11A, warrant future monitoring in IPD owing to invasive potential and/or antibiotic resistance rates.

Expression of microRNA-21 and TIMP-3 in paradoxical psoriasiform reactions during treatment with antitumor necrosis factor agents.

BACKGROUND: Expression of microRNA-21 (miR-21) is increased in psoriasis, leading to reduced levels of epidermal tissue inhibitor of matrix metalloproteinase 3 (TIMP-3), a highly potent inhibitor of the tumor necrosis factor alpha (TNFα) sheddase TACE (TNFα-converting enzyme)/ADAM17. We described the profile of miR-21 and TIMP-3 in paradoxical psoriasiform reactions induced by anti-TNFα drugs and in a control group to elucidate the pathogenesis of this reactions. METHODS: We performed an analytic, cross-sectional, prospective, experimental case-control study. We compared our findings with those of non-induced psoriasis. RESULTS: We included 15 patients with a change of morphology (plaque to guttate psoriasis) and 10 patients with induced psoriasis (six palmoplantar pustulosis and four plaque psoriasis). Consecutive patients with different subtypes of non-induced, non-systemically treated psoriasis were included as a control group. We found that most cases with guttate psoriasis and with induced plaque psoriasis cases showed high expression of TIMP-3 expression and decreased or poorly increased levels of miR-21. The expression pattern was not homogeneous in the cases of induced palmoplantar pustulosis. These profiles differ from those of non-induced psoriasis. CONCLUSION: We conclude that various pro-inflammatory cytokine profiles are involved in the pathogenesis of paradoxical psoriasiform reactions and non-induced psoriasis.

Complications Associated with Mohs Micrographic Surgery: Data from the Nationwide Prospective Cohort REGESMOHS.

BACKGROUND: Large prospective studies on the safety of Mohs micrographic (MMS) surgery are scarce, and most focus on a single type of surgical adverse event. Mid-term scar alterations and functional loss have not been described. OBJECTIVES: To describe the risk of MMS complications and the risk factors for them. METHODS: A nationwide prospective cohort collected all adverse events on consecutive patients in 22 specialised centres. We used multilevel mixed-effects logistic regression to find out factors associated with adverse events. RESULTS: 5,017 patients were included, with 14,421 patient-years of follow-up. 7.0% had some perioperative morbidity and 6.5% had mid-term and scar-related complications. The overall risk of complications was mainly associated with use of antiaggregant/anticoagulant and larger tumours, affecting deeper structures, not reaching a tumour-free border, and requiring complex repair. Age and outpatient setting were not linked to the incidence of adverse events. Risk factors for haemorrhage (0.9%) were therapy with antiaggregant/anticoagulants, tumour size, duration of surgery, and unfinished surgery. Wound necrosis (1.9%) and dehiscence (1.0%) were associated with larger defects and complex closures. Immunosuppression was only associated with an increased risk of necrosis. Surgeries reaching deeper structures, larger tumours and previous surgical treatments were associated with wound infection (0.9%). Aesthetic scar alterations (5.4%) were more common in younger patients, with larger tumours, in H-area, and in flap and complex closures. Risk factors for functional scar alterations (1.7%) were the need for general anaesthesia, larger tumours that had received previous surgery, and flaps or complex closures. CONCLUSIONS: MMS shows a low risk of complications. Most of the risk factors for complications were related to tumour size and depth, and the resulting need for complex surgery. Antiaggregant/anticoagulant intake was associated with a small increase in the risk of haemorrhage, that probably does not justify withdrawal. Age and outpatient setting were not linked to the risk of adverse events.

Fatty Acid and Tocopherol Composition of Pomace and Seed Oil from Five Grape Varieties Southern Spain.

Grape pomace and seeds are important winemaking by-products. Their oils are rich in bioactive compounds such as fatty acids and tocopherols. We have characterized oils from both by-products from five Spanish grape varieties (Palomino Fino, Pedro Ximénez, Muscat of Alexandria, Tempranillo and Tintilla de Rota). A high content of UFAs was found in all the analyzed samples. Grape pomace oils generally had the same oleic acid (PUFAω-6) content as seed oils, and lower PUFA contents; they also had a markedly higher linolenic acid (PUFAω-3) content, improving the PUFAω-6/PUFAω-3 ratio. All the oil studied show good indicators of nutritional quality: low values of the atherogenicity (0.112-0.157 for pomace, 0.097-0.112 for seed) and thrombogenicity indices (0.30-0.35 for pomace, 0.28-0.31 for seed) and high values of the relationship between hypo- and hypercholesterolemic fatty acids (6.93-9.45 for pomace, 9.11-10.54 for seed). Three tocopherols were determined: α-, γ- and δ-tocopherol. Pomace oils have higher relative contents of α- and δ-tocopherol, whereas seed oils have higher relative contents of γ-tocopherol. A significantly higher content of total tocopherols has been found in pomace oil; it is higher in the oils from red varieties of pomace (628.2 and 706.6 mg/kg by-product), and in the oils from pomace containing stems (1686.4 mg/kg by-product). All the oils obtained can be considered as a source of vitamin E, and their consumption is beneficial for health.

Mohs micrographic surgery in dermatofibrosarcoma protuberans: Rate and risk factors for recurrence in a prospective cohort study from the Spanish Registry of Mohs Surgery (REGESMOHS) and review of the literature.

Characterization of patients, surgery procedures and the risk factors for dermatofibrosarcoma protuberans (DFSP) recurrences is poorly defined. In this study, we aimed to describe the demographics, tumor characteristics and interventions of DFSP treated with Mohs micrographic surgery (MSS) to determine the rate and risk factors for recurrence. Data were collected from REGESMOHS, a nationwide prospective cohort study of patients treated with MMS in Spain. From July 2013 to February 2020, 163 patients with DFSP who underwent MMS were included. DFSP was mostly located on trunk and extremities. Recurrent tumors had deeper tumor invasion and required higher number of MMS stages. Paraffin MMS was the most frequently used technique. Overall recurrence rate was 0.97 cases/100 person-years (95% IC = 0.36-2.57). No differences were found in epidemiological, tumor, surgery characteristics or surgical technique (frozen or paraffin MMS [p = 0.6641]) in terms of recurrence. Median follow-up time was 28.6 months with 414 patient-years of follow-up. In conclusion, we found an overall low recurrence rate of DFSP treated with MMS. None of the studied risk factors, including MMS techniques, was associated with higher risk for recurrence.

Geometric border as a marker for melanoma diagnosis: Study of 200 consecutive melanocytic lesions.

The ABCD rule has long been proposed as a guidance for malignant melanoma (MM) diagnosis. We aimed to define a new simple, straightforward tool that could be useful in early melanoma detection and must be validated in further studies. We conducted a prospective historic cohort study of 200 melanocytic lesions classifying them according to the presence of geometric borders. Sixty-four percent of the MM and 31% of the melanocytic nevi presented with geometric borders. Lesions with two straight borders that formed a noncurvilinear angle presented a 2.1-fold higher risk of being malignant after excision. When comparing melanomas with geometric and nongeometric border, we found a tendency toward better prognostic markers in the geometric lesions. Lesions located in the extremities and melanoma subtype SSM were more common in the geometric group. Regarding pathologic features, a deeper Breslow (mean, 3.8 vs 1.4 mm), presence of ulceration (25% vs 5%) and a higher number of mitosis was found in the nongeometric group. On the other hand, more regression was found in the geometric group while both groups showed similar degree of lymphovascular infiltration. We propose geometric border as another clinical criterion to take into account when suspecting MM, which must be validated in further studies. The ABCDE rule could be completed with a G for geometry.

Risk Factors and Rate of Recurrence after Mohs Surgery in Basal Cell and Squamous Cell Carcinomas: A Nationwide Prospective Cohort (REGESMOHS, Spanish Registry of Mohs Surgery).

Randomized studies to assess the efficacy of Mohs micrographic surgery in basal cell and squamous cell carcinomas are limited by methodological and ethical issues and a lack of long follow-up periods. This study presents the "real-life" results of a nationwide 7-years cohort on basal cell carcinoma and squamous cell carcinoma treated with Mohs micrographic surgery. A prospective cohort was conducted in 22 Spanish centres (from July 2013 to February 2020) and a multivariate analysis, including characteristics of patients, tumours, surgeries and follow-up, was performed. A total of 4,402 patients followed up for 12,111 patient-years for basal cell carcinoma, and 371 patients with 915 patient-years of follow-up for squamous cell carcinoma were recruited. Risk factors for recurrence included age, non-primary tumours and more stages or unfinished surgeries for both tumours, and immunosuppression for squamous cell carcinoma. Incidence rates of recurrence were 1.3 per 100 person-years for basal cell carcinoma (95% confidence interval 1.1-1.5) and 4.5 for squamous cell carcinoma (95% confidence interval 3.3-6.1), being constant over time (0-5 years). In conclusion, follow-up strategies should be equally intense for at least the first 5 years, with special attention paid to squamous cell carcinoma (especially in immunosuppressed patients), elderly patients, non-primary tumours, and those procedures requiring more stages, or unfinished surgeries.

Is it useful to evaluate the presence of aberrant right subclavian artery in prenatal diagnosis ultrasounds?

AIM: Analyze if the evaluation of aberrant right subclavian artery in the prenatal echography has improved the detection of chromosomal, genetic and/or morphological abnormalities in our population. METHODS: Descriptive, observational, cross-sectional study of the cases of aberrant right subclavian artery diagnosed in our Prenatal Diagnosis Unit between January of 2011 and December of 2018. RESULTS: Two hundred and fifty-seven cases of aberrant right subclavian artery were diagnosed and among them, 179 were considered isolated cases and thus were confirmed after birth. The detection of aberrant right subclavian artery did not improve itself neither the diagnosis of trisomy 21 in the second trimester of pregnancy nor other chromosomal or genetic abnormalities, including the not isolated cases. There were two cases of trisomy 21 diagnosed in the second trimester that presented major sonographic disorders and an inadequate examination during the first trimester. When aberrant right subclavian artery was associated with soft markers of aneuploidy in the second trimester, any case was a trisomy 21. Aberrant right subclavian artery seems to be associated with some minor and major heart defects, especially ventriculoseptal defect and aneurismatic ductus, and in some cases, also with clubfeet. CONCLUSION: When an adequate screening of aneuploidies and a thorough ultrasound have been performed during the first trimester, aberrant right subclavian artery hardly helps to perform other diagnosis in the second trimester.

A Real-Time Method for Improving Stability of Monolithic Quartz Crystal Microbalance Operating under Harsh Environmental Conditions.

Monolithic quartz crystal microbalance (MQCM) has recently emerged as a very promising technology suitable for biosensing applications. These devices consist of an array of miniaturized QCM sensors integrated within the same quartz substrate capable of detecting multiple target analytes simultaneously. Their relevant benefits include high throughput, low cost per sensor unit, low sample/reagent consumption and fast sensing response. Despite the great potential of MQCM, unwanted environmental factors (e.g., temperature, humidity, vibrations, or pressure) and perturbations intrinsic to the sensor setup (e.g., mechanical stress exerted by the measurement cell or electronic noise of the characterization system) can affect sensor stability, masking the signal of interest and degrading the limit of detection (LoD). Here, we present a method based on the discrete wavelet transform (DWT) to improve the stability of the resonance frequency and dissipation signals in real time. The method takes advantage of the similarity among the noise patterns of the resonators integrated in an MQCM device to mitigate disturbing factors that impact on sensor response. Performance of the method is validated by studying the adsorption of proteins (neutravidin and biotinylated albumin) under external controlled factors (temperature and pressure/flow rate) that simulate unwanted disturbances.

Detection of DDT and carbaryl pesticides in honey by means of immunosensors based on high fundamental frequency quartz crystal microbalance (HFF-QCM).

BACKGROUND: In recent years there has been a concern about the presence of pesticides in honey because residues of DDT and carbaryl were found in honey samples. Traditional techniques, such as chromatography, reach the required limits of detection (LOD) but are not suitable for in situ implementation in the honey-packaging industry due to their high cost and the need for highly qualified staff for routine operation. Biosensors offer simplicity, low cost, and easy handling for analytical purposes in food applications. RESULTS: Piezoelectric immunosensors based on high fundamental frequency quartz crystal microbalance (HFF-QCM) have been developed for the detection of carbaryl and DDT in honey. Biorecognition was based on competitive immunoassays in the conjugate-coated format, using monoclonal antibodies as specific immunoreagents. The assay LODs attained by the HFF-QCM immunosensors were 0.05 µg L-1 for carbaryl and 0.24 µg L-1 for DDT, reaching a similar level of detectability to that of the usual reference techniques. The practical LODs in honey samples were 8 µg kg-1 for carbaryl and 24 µg kg-1 for DDT. The immunosensors' analytical performance allow the detection of these pesticides in honey at EU regulatory levels with good accuracy (recovery percentages ranging from 94% to 130% within the working range of each pesticide standard curve) and precision (coefficients of variation in the 9-36% range). CONCLUSION: The proposed immunosensor is a promising analytical tool that could be implemented for quality control in the honey packaging industry, to simplify and to reduce the cost of the routine pesticide analysis in this appreciated natural food. © 2020 Society of Chemical Industry.

Effect of Drying on the Phenolic Content and Antioxidant Activity of Red Grape Pomace.

Winemaking by-products are considered to be a rich source of bioactive compounds. Grape pomace is susceptible to microbial degradation due to the degree of residual moisture, so the drying of this pomace for conservation is considered to be an essential first step. Previous studies concerning the way in which drying affects winery by-products have produced contradictory results. In this study, a new methodology for drying grape pomace in a climatic chamber has been evaluated. Five red grape pomace varieties were dried in a climatic chamber at 40 °C and 10% relative humidity and the phenolic content and antioxidant activity of the dried and wet pomace samples were compared. The results indicate that this drying process is both feasible and beneficial because significant increases in the extractability of phenolic compounds and antioxidant activity were achieved.

Design and Validation of a 150 MHz HFFQCM Sensor for Bio-Sensing Applications.

Acoustic wave resonators have become suitable devices for a broad range of sensing applications due to their sensitivity, low cost, and integration capability, which are all factors that meet the requirements for the resonators to be used as sensing elements for portable point of care (PoC) platforms. In this work, the design, characterization, and validation of a 150 MHz high fundamental frequency quartz crystal microbalance (HFF-QCM) sensor for bio-sensing applications are introduced. Finite element method (FEM) simulations of the proposed design are in good agreement with the electrical characterization of the manufactured resonators. The sensor is also validated for bio-sensing applications. For this purpose, a specific sensor cell was designed and manufactured that addresses the critical requirements associated with this type of sensor and application. Due to the small sensing area and the sensor's fragility, these requirements include a low-volume flow chamber in the nanoliter range, and a system approach that provides the appropriate pressure control for assuring liquid confinement while maintaining the integrity of the sensor with a good base line stability and easy sensor replacement. The sensor characteristics make it suitable for consideration as the elemental part of a sensor matrix in a multichannel platform for point of care applications.

[Clinical and epidemiological differences between Bordetella pertussis and respiratory syncytial virus infections in infants: a matched case control study]. / Diferencias clínicas y epidemiológicas entre las infecciones por Bordetella pertussis y por virus respiratorio sincitial en lactantes: estudio de casos controles emparejados.

INTRODUCTION: An increase in cases of pertussis, mainly in young infants, has been reported in the last few years. The clinical presentation of this disease is very similar to that produced by respiratory syncytial virus (RSV), which makes the diagnosis difficult. OBJECTIVE: To compare the clinical and epidemiological characteristics between Bordetella pertussis and RSV infections in infants admitted to hospital. MATERIAL AND METHODS: An analytical matched case-control study was conducted during the period 2008-2011. Cases were defined as infants admitted with pertussis confirmed by PCR in nasopharyngeal aspirate. Each case was matched by age, sex and date of admission to two controls defined as patients with RSV infection detected by immunochromatography in nasal aspirate. Demographic, clinical, laboratory data were compared. RESULTS: Seventy eight patients (26 cases of pertussis and 52 controls RSV+) were included. Sociodemographic characteristics were similar in both groups. Cases had more days of symptoms prior to admission, longer hospital stays, and increased frequency of epidemic family environment. Apnoea and cyanosis were more frequent. Cases of pertussis were more likely to have apnoea, cyanosis, and lymphocytosis while RSV infections had more frequent fever, vomiting and respiratory distress. CONCLUSIONS: The clinical presentations of pertussis and RSV infection are similar, but there are some characteristics that can help to distinguish between them.

Love wave immunosensor for the detection of carbaryl pesticide.

A Love Wave (LW) immunosensor was developed for the detection of carbaryl pesticide. The experimental setup consisted on: a compact electronic characterization circuit based on phase and amplitude detection at constant frequency; an automated flow injection system; a thermal control unit; a custom-made flow-through cell; and Quartz /SiO2 LW sensors with a 40 µm wavelength and 120 MHz center frequency. The carbaryl detection was based on a competitive immunoassay format using LIB-CNH45 monoclonal antibody (MAb). Bovine Serum Albumin-CNH (BSA-CNH) carbaryl hapten-conjugate was covalently immobilized, via mercaptohexadecanoic acid self-assembled monolayer (SAM), onto the gold sensing area of the LW sensors. This immobilization allowed the reusability of the sensor for at least 70 assays without significant signal losses. The LW immunosensor showed a limit of detection (LOD) of 0.09 µg/L, a sensitivity of 0.31 µg/L and a linear working range of 0.14-1.63 µg/L. In comparison to other carbaryl immunosensors, the LW immunosensor achieved a high sensitivity and a low LOD. These features turn the LW immunosensor into a promising tool for applications that demand a high resolution, such as for the detection of pesticides in drinking water at European regulatory levels.