Laboratory validation of an ELISA method to measure circulating immune complexes levels in canine visceral leishmaniasis.

Susceptible dogs suffering from canine leishmaniasis (CanL) develop an ineffective humoral immune response that leads to the formation of circulating immune complexes (CIC). These CIC are aggregates of Leishmania proteins and anti-Leishmania immunoglobulins. Their deposition in different tissues is considered the main cause of mortality. For this reason, CIC have been suggested as an excellent CanL biomarker for measuring the progression of the disease and the effectiveness of specific treatments. The present study aims to perform a laboratory validation of a Leishmania-specific method to isolate and quantify CIC in dog serum samples. CIC isolated from serum samples of infected dogs, grouped according to the LeishVet classification, were quantified following a PEG-ELISA procedure. The validation established a cut-off of 0.274 OD. All the parameters analyzed (including linearity, specificity, precision, and robustness) fulfilled the defined criteria, confirmed by statistical analyses. The results also proved the reproducibility and reliability of the method when samples were tested under the same conditions, and the consistency and usefulness of the method for an optimal staging of infected dogs. In conclusion, the laboratory validated method offers a potent tool to clinicians for a proper CanL management and to measure the progression of the disease.

Spectrum of comorbid autoimmune diseases in patients with chondrodermatitis nodularis helicis: a 17-year retrospective study of 215 patients in Asturias, northern Spain

Background: The cause of chondrodermatitis nodularis helicis (CN) (Winkler's disease) is unknown, but potential associations with autoimmune diseases have been suggested in case reports, however, studies with large case series are lacking. Objectives: To clarify the frequency of chronic inflammatory and autoimmune diseases (CADs), and associated gender and age distribution, in a large cohort of patients with CN. Materials & Methods: The frequency of CADs (systemic and cutaneous) was assessed in 215 patients (65.1% males and 34.9% females; median age: 69.6 years) with a histopathological diagnosis of CN (2000-2017). Endocrine diseases were not included. Statistical analysis included Fisher's exact test and multivariate logistic regression analysis. Results: Twenty different CADs were diagnosed in 15.34% patients with CN. The most frequent were polymyalgia rheumatica (six patients), psoriasis (four patients, one with psoriatic arthritis), rheumatoid arthritis (three patients), CREST syndrome (two patients), vitiligo (two patients), and chronic dermatitis (two patients). Several CADs were strongly associated with tobacco smoking. Systemic CADs were more frequent in females (OR: 3.814; CI 1.513-9.613; p = 0.005; multivariate logistic regression analysis). Differences according to age at onset were not significant. Conclusion: We characterize, for the first time, the spectrum of CADs as well as age and gender distribution in patients with CN based on the largest cohort of patients to date. The possible accumulation of different disorders that are strongly associated with tobacco smoking (Buerger's disease, pulmonary Langerhans cell histiocytosis, rheumatoid arthritis, Lupus erythematosus, and others) merits further investigation, but the rarity of some of them makes this challenging.

Retrospective study of apremilast drug survival in psoriasis patients in a daily practice setting: A long-term experience.

There is limited evidence about the real-world survival of apremilast in patients with psoriasis, especially over the long term. To evaluate the long-term survival of apremilast and its predictive factors when used to treat psoriasis. A retrospective hospital-based study, including data collected from 104 patients. Survival curves were estimated using the Kaplan-Meier estimator. Proportional hazard Cox regression models were used for multivariate analysis. The average duration of the treatment before discontinuation was 28.82 months (95% CI, 22.08-35.57 months) and the median was 12 months (95% CI, 2.68-21.31 months). The retention rates were 51% (1 year), and 33% (5 years). The survival study revealed statistically significant differences between patients with PASI<10 and those in the PASI≥10 group (log-rank test, p < 0.001). The 5-year prevalences were 64% for patients with a PASI of <10 and 5% for those with an index ≥10. In the PASI < 10-patient group, the retention rates were 77% (1 year) and 64% (5 years). Furthermore, 66% of patients who continued apremilast treatment for more than 2 years were receiving off-label doses (30 mg/day). Apremilast may be a suitable and efficient alternative for the treatment of psoriasis patients in the PASI<10 group.

Use of Biological Treatments in Elderly Patients with Skin Psoriasis in the Real World.

Biological drugs have prompted a revolution in the treatment of patients with psoriasis because of their favourable efficacy/risk profile. The aims of our study are to determine whether there is any difference in the pattern of use of biological treatments for older (65+ years) and younger patients diagnosed with plaque psoriasis by the Dermatology Service of the Hospital Universitario de Asturias (HUCA), to understand the survival of these drugs, and to identify the factors that predict the discontinuation of treatments. We report a retrospective observational hospital-based study of 300 patients registered at HUCA's Dermatology Service who were receiving one of the following biological treatments for psoriasis on 30 November 2020: adalimumab, ustekinumab, secukinumab, or ixekizumab. The age groups were compared using Student's t-test for quantitative variables and the chi-squared test for qualitative variables. We used the Kaplan-Meier estimator to estimate the survival function and the log-rank test to measure differences. No statistically significant differences in the frequency of use were noted between the younger and older groups, for any of the drugs studied. Survival on a drug regime, globally and individually, was similar in the two age groups. Factors predicting lower overall survival were being female, obesity, and having undergone previous biological treatment. The first three factors were influential in the under-65-year-old group, while arthritis was a significant factor for the older group.

Dermatitis anular liquenoide de la infancia / Annular lichenoid dermatitis of youth

No disponible

Ustekinumab Drug Survival in Patients with Psoriasis: A retrospective Study of Real Clinical Practice.

Background and objectives: The efficacy and safety of ustekinumab have been proved in clinical trials. In daily clinical practice, knowing the factors that determine survival differences of biological drugs allows psoriasis treatment to be optimized as a function of patient characteristics. The main objectives of this work are to understand ustekinumab drug survival in patients diagnosed with plaque psoriasis in the Hospital Universitario Central de Asturias (HUCA Dermatology Department, and to identify the predictors of drug discontinuation. Materials and Methods: A retrospective hospital-based study, including data from 148 patients who were receiving ustekinumab (Stelara®) between 1 February 2009 and 30 November 2019, were collected. Survival curves were approximated through the Kaplan-Meier estimator and compared using the log-rank test. Proportional hazard Cox regression models were used for multivariate analyses while both unadjusted and adjusted hazard ratios (HR) were used for summarizing the studied differences. Results: The average duration of the treatment before discontinuation was 47.57 months (SD 32.63 months; median 41 months). The retention rates were 82% (2 years), 66% (5 years), and 58% (8 years). Median survival was 80 months (95% confidence interval. CI 36.9 to 123.01 months). The survival study revealed statistically significant differences between patients with arthritis (log-rank test, p < 0.001) and those who had previously received biological treatment (log-rank test, p = 0.026). The five-year prevalence in patients still under treatment was 80% (those without arthritis) and 54% (arthritis patients). In the multivariate analysis, only the patients with arthritis had a lower rate of drug survival. No statistically significant differences were observed for any of the other comorbidities studied. The first and second most frequent causes of discontinuation were secondary failure and arthritis inefficacy, respectively. Conclusion: Ustekinumab is a biological drug conferring high survival in plaque psoriasis patients. Ustekinumab survival is lower in patients with arthritis.

Vaccination with LetiFend® reduces circulating immune complexes in dogs experimentally infected with L. infantum.

Domestic dogs constitute the main reservoir of Leishmania infantum and play a key role in transmission to humans. The main tool for controlling infection spread is a safe and effective vaccine, as successful immunization of dogs could significantly reduce the incidence of human visceral leishmaniosis (VL) and is the most cost-effective control strategy. The factors that determine disease progression in canine leishmaniosis (CanL) remain poorly understood, though a previous study in naturally infected dogs has demonstrated a clear relationship between the presence of circulating immune complexes (CIC) in the blood and disease progression. Thus, the aim of this study was to compare CIC levels in serum samples from dogs vaccinated or unvaccinated with LetiFend®, a new vaccine containing recombinant Protein Q, and experimentally infected with L. infantum. CIC were isolated from vaccinated or unvaccinated dogs after experimental infection with L. infantum and their levels measured by ELISA. Furthermore, reverse phase-liquid chromatography-mass spectrometry (RP-LC-MS/MS) analysis was used to investigate the protein composition of precipitated CIC. At all the time points analyzed after infection, the amount of CIC was lower in the vaccinated group compared to the placebo group. Furthermore, there were differences in the protein composition of precipitated CIC between the vaccinated and unvaccinated groups. In conclusion, administration of LetiFend® was able to reduce CIC elicited after experimental infection with L. infantum in a dog model in a process that may be related to complement system activation.

Circulating immune complexes levels correlate with the progression of canine leishmaniosis in naturally infected dogs.

Dogs are the main domestic reservoir of Leishmania infantum, and in cases of uncontrolled infection, a strong humoral immune response is elicited, which is inefficient against the parasites. Previous studies have suggested that an adequate antigen/antibody ratio, with a moderate prevalence of antigens with respect to the antibodies, could result in the formation of circulating immune complexes (CIC) in canine leishmaniosis (CanL). Deposition of these complexes in tissues has been associated with vasculitis, uveitis, arthritis, dermatitis and especially glomerulonephritis and renal failure. However, little is known about the relationship between the presence of CIC and disease progression. The aim of this study was to evaluate serum CIC level and its correlation with disease severity in infected dogs with different stages of disease and non-infected animals as a control. A total of 60 dogs were included in the study, classified according to the proposed LeishVet classification criteria: healthy non-infected (n = 13); healthy infected (n = 12); sick stage I (n = 9); sick stage II (n = 17); sick stage III (n = 8); and sick stage IV (n = 1). CIC were isolated from serum samples using a modified polyethylene glycol precipitation method, and their levels measured by ELISA and bicinchoninic acid protein assay. A nanoparticle tracking analysis was performed to investigate the relationship between the molecular size distribution of the CIC and disease progression. In conclusion, the results confirmed a positive association between CIC levels, their molecular size and disease progression that suggests a potential use of CIC as biomarkers of CanL.

Correlation of focal adhesion kinase expression with nodal metastasis in patients with head and neck cutaneous squamous cell carcinoma.

BACKGROUND: Focal adhesion kinase (FAK) and cortactin overexpression is frequently detected in a variety of cancers, and has been associated with poor clinical outcome. However, there are no data in cutaneous squamous cell carcinoma (cSCC). OBJECTIVE: To investigate the relationship of FAK and cortactin expression with the clinicopathologic features and the impact on the prognosis of cSCC patients. METHODS: FAK and cortactin expression was analyzed by immunohistochemistry on paraffin-embedded tissue samples from 100 patients with cSCC, and correlated with the clinical data. RESULTS: FAK overexpression was a significant risk factor for nodal metastasis with crude and adjusted ratios (HRs) of 2.04, (95% CI [1.08-3.86], [P = 0.029]) and 2.23 (95% CI [1.01-4.91], [P = 0.047]), respectively. Cortactin expression was not a significant risk factor for nodal metastasis. CONCLUSION: These findings demonstrate that FAK overexpression is an independent predictor of nodal metastasis that might be helpful for risk stratification and management of patients with cSCC.

Unusual presentation of herpes simplex virus infection in a boxer: 'Boxing glove herpes'.

Herein, we describe a patient with lesions of cutaneous herpes simplex virus 1 (HSV-1) infection over the knuckles of both hands in the context of an outbreak among boxers. Interestingly, the infection had an unusually long duration (4 weeks), and was not acquired directly through skin-to-skin contact, as it usually does among athletes (herpes gladiatorum). In our case, transmission was acquired through the use of shared boxing gloves contaminated by HSV-1. To the best of our knowledge, herpes gladiatorum, or wrestler's herpes, has not been described previously in boxers and infection over the knuckles is not commonly reported.

Psoriasis and type 2 diabetes risk among psoriatic patients in a Spanish population.

There is accumulating evidence showing a relationship between psoriasis and an increased risk of developing cardiovascular risk factors, including diabetes mellitus type 2 and ischemic heart disease. Our aim was to investigate if there is any difference in the diabetes risk profile among psoriatic patients based on clinical findings. To test this, we carried out a prospective and descriptive hospital-based study. Our results suggest that the highest risk of suffering from diabetes mellitus type 2 among psoriatic patients is in patients suffering from non-familial and late-onset disease and in patients suffering from psoriatic arthritis.

Liver growth factor promotes the survival of grafted neural stem cells in a rat model of Parkinson's disease.

Neural stem cells (NSCs) with self-renewal and multilineage potential are considered good candidates for cell replacement of damaged nerve tissue. Several studies have focused on the ability of the neurotrophic factors coadministration to improve the efficiency of grafted NSCs. Liver growth factor (LGF) is an hepatic mitogen that promotes regeneration of damaged tissues, including brain tissue. It has neurogenic activity and has partially restored the nigrostriatal dopaminergic system in an experimental model of Parkinson's disease. Present results demonstrate that in the dopamine- depleted striatum of 6-hydroxydopamine-lesioned rats, grafted NSCs retained their ability to differentiate into neurons, astrocytes, and oligodendrocytes. NSCs also differentiated into microglia/macrophages and endothelial cells. Thus, 23 ± 5.6% of them were inmunoreactive for isolectin IB4, and a small population integrated into blood vessels, showing an endothelial-like morphology. Intrastriatal infusion of LGF promoted the viability of the implants, and favored their differentiation to an endothelial-like phenotype. Moreover, LGF infusion raised the expression of the anti-apoptotic protein Bcl-2 by 3.9 ± 0.9 fold without affecting the levels of the pro-apoptotic protein Bax. Since LGF-treated rats also showed a significant reduction in apomorphine-induced rotational behavior, our results suggest that administration of this factor might be a convenient treatment for Parkinson's disease cell replacement therapies based on NSCs transplantation.

Fiabilidad y validez de la versión españolade una escala de autoeficaciaen la lactancia materna / Reliability and validity of the Spanish version of a breastfeeding self-efficacy scale

Objetivo: El objetivo de este trabajo es validar lingüísticamente laBreastfeeding Self-Efficacy Scale-Short Form (BSES-SF) al español y determinarsus características psicométricas.Personas y método: Estudio instrumental que se llevó a cabo en doshospitales de la provincia de Alicante. Tras los procedimientos de traduccióny retrotraducción, una muestra accidental de 150 madres lactantescumplimentaron, a las 48 horas del parto y aún hospitalizadas,la versión española de la BSES-SF y un cuestionario con variables sociodemográficas,obstétricas y sobre el estatus de lactancia materna (LM)al alta. A las 6 semanas posparto se obtuvieron, nuevamente, datos sobreel estatus de LM mediante una encuesta telefónica.Resultados: El coeficiente alfa de Cronbach fue de 0,79. Las mujerescon experiencia previa y con experiencia previa muy positiva en LM, conpuntuaciones más altas en el ítem global de autoeficacia y con máshijos, tuvieron mayores puntuaciones en la versión española de laBSES-SF. Dos de los ítems (9 y 10) de la versión española presentaroncorrelaciones ítems-test corregidas <0,30, y saturaron por debajo de0,30 al forzar la extracción a un factor en el análisis de componentesprincipales. Las puntuaciones de la escala al alta hospitalaria no guardaronrelación con el estatus de LM a las 6 semanas posparto.Conclusiones: El instrumento muestra aceptables evidencias de fiabilidady validez, aunque dos de los ítems deberían ser revisados (AU)

Aim: To translate the Breastfeeding Self-Efficacy Scale-Short Form(BSES-SF) into Spanish and assess its psychometric properties.Subjects and method: Instrumental study took place in two hospitalsin the Spanish region of Alicante. Following translation andback-translation procedures, an accidental sample of 150 mothersbreastfeeding (BF) their babies, completed, at 48 hours after deliveryand still hospitalized, the Spanish version of the BSES-SF and a questionnairewith socio demographic, obstetric and BF variables. At 6weeks postpartum data on the status of BF were obtained again,through a telephone survey.Results: The Cronbach’s alpha coefficient was of 0.79. Women withprevious experience and with very positive prior experience in BF, withhigher scores on the global item of self-efficacy and with previous childrenhad higher scores on the Spanish version of the BSES-SF. Two ofthe items (9 and 10) of the Spanish version show item-corrected testcorrelations <0.30 and saturated below 0.30 in the analysis of principalcomponents when one factor was forced. The scores at discharge werenot related to the status of BF at 6 weeks postpartum.Conclusions: The instrumental study shows acceptable evidencesof reliability and validity, although two of the items should be reviewed (AU)

Psoriasis induced by cetuximab: a paradoxical adverse effect.

Cetuximab, an epidermal growth factor receptor inhibitor, is a chemotherapeutical agent featuring well-known adverse dermatological effects related to tumour-response prognosis. In psoriasis, the epidermal growth factor receptor is overexpressed; hence, the expectation would be that an epidermal growth factor receptor inhibitor could improve psoriatic lesions. We report a case of psoriasis induced by cetuximab, which was a surprising adverse effect.

Mobilization of neural stem cells and generation of new neurons in 6-OHDA-lesioned rats by intracerebroventricular infusion of liver growth factor.

Neural stem cells with self-renewal and multilineage potential persist in the subventricular zone of the adult mammalian forebrain. These cells remain relatively quiescent but, under certain conditions, can be stimulated, giving rise to new neurons. Liver growth factor (LGF) is a mitogen for liver cells that shows biological activity in extrahepatic sites and is useful for neuroregenerative therapies. The aim of this study was to investigate the potential neurogenic activity of LGF in the 6-hydroxydopamine rat model of Parkinson's disease. Proliferation was significantly increased in the subventricular zone and denervated striatum of rats receiving ICV LGF infusions, and 25% of the proliferating cells were doublecortin-positive neurons. Doublecortin-positive cells with the morphology of migrating neuroblasts were also observed in the dorsal and ventral regions of the striatum of LGF-infused animals. Moreover, some newly generated cells were neuronal nuclei-positive mature neurons. LGF also stimulated microglia and induced astrogliosis, both phenomena associated with generation and migration of new neurons in the adult brain. In summary, our study shows that LGF stimulates neurogenesis when applied intraventricularly in 6-hydroxydopamine-lesioned rats. Considering that this factor also promotes neuronal migration into damaged tissue, we propose LGF as a novel factor useful for neuronal replacement in neurodegenerative diseases.

Driving neural stem cells towards a desired phenotype.

Neural stem cells are defined as clonogenic cells with self-renewal capacity and the ability to generate all neural lineages. Cells with these characteristics have been isolated from the embryonic and adult Central Nervous System. Numerous reports show that extrinsic factors and intracellular mechanisms may trigger both endogenous and in vitro cultured neural stem cells to differentiate into desired cell outcomes. This plasticity opens new approaches for the use of neural stem cells as a source of cells for replacement therapy in damaged brain. In this review we present the evidence for the involvement of trophic factors, neurotransmitters, second messengers, aminoacids, and factors released by endothelial and glial cells, which have been reported to influence neural stem cells phenotypic choice in vitro and in vivo.

Síndrome auriculotemporal de Frey. Un caso de presentación bilateral en un lactante / Frey auriculotemporal syndrome. A bilateral case in a child

El síndrome auriculotemporal o síndrome de Frey se caracteriza por la aparición de enrojecimiento, hiperhidrosis, o ambos, en la zona inervada por elnervio auriculotemporal como respuesta a un estímulo gustativo desencadenado por la ingesta de distintos alimentos. Por este motivo puede confundirseen ocasiones con alergias alimentarias. Se debe generalmente a una lesión del nervio auriculotemporal, si bien en ocasiones no existe ningún antecedentetraumático. Su aparición en la infancia y su presentación bilateral, como el caso que presentamos a continuación, son muy poco frecuentes

Frey syndrome or auriculotemporal nerve syndrome manifests as flushing, sweating, or both, localized to the distribution of the auriculotemporal nerve,in response to gustatory stimuli. Ocasionally it may be misinterpreted as foog allergy. It usually occurs as a result of injury to auriculotemporal nerve, butthere are cases with no known previous trauma. It is rarely described in children as well as the bilateral involvement, as the case we presented