Moderate to Severe Psoriasis in Pediatric and Young Patients: The BIOBADADERM Registry Experience. / Psoriasis moderada-grave en pacientes pediátricos y jóvenes: experiencia en el registro BIOBADADERM.

Childhood-onset psoriasis generally follows an indolent course but patients with moderate or severe disease may require systemic treatment. The aim of this study was to determine the relative proportion of children and young people aged up to 21 years with moderate to severe psoriasis in the BIOBADADERM registry and to analyze the characteristics of these patients, treatments used, and adverse events. Of the 3946 patients in the registry, 24 were aged 21 years or younger. They had mean age of 16.1 years on starting treatment. When the registry was started, they had a Psoriasis Area and Severity Index of 9.4 and 67% were being treated with a conventional systemic drug. Treatment was discontinued in 14 patients (58%) due to adverse events or a loss or lack of effectiveness. In conclusion, the BIOBADADERM registry shows that young people account for a small proportion of psoriasis patients receiving systemic treatment, and they are more likely to be treated using conventional systemic drugs.

Acinar inflammatory response to lipid derivatives generated in necrotic fat during acute pancreatitis.

Lipids play a role in acute pancreatitis (AP) progression. We investigate the ability of pancreatic acinar cells to trigger inflammatory response in the presence of lipid compounds generated in necrotic areas of peripancreatic adipose tissue (AT) during AP induced in rats by 5% sodium taurocholate. Lipid composition of AT was analyzed by HPLC-mass spectrometry. Acinar inflammatory response to total lipids as well as to either the free fatty acid (FFA) fraction or their chlorinated products (Cl-FFAs) was evaluated. For this, mRNA expression of chemokine (C-C motif) ligand 2 (CCL2) and P-selectin as well as the activation of MAPKs, NF-κB and STAT-3 were analyzed in pancreatic acini. Myeloperoxidase (MPO) activity, as an inducer of Cl-FFA generation, was also analyzed in AT. MPO activity significantly increased in necrotic (AT-N) induced changes in lipid composition of necrotic fat, such as increase in FFA and phospholipid (PL) content, generation of Cl-FFAs and increases in saturated FFAs and in the poly-:mono-unsaturated FFA ratio. Total lipids from AT-N induced overexpression of CCL2 and P-selectin in pancreatic acini as well as MAPKs phosphorylation and activation of NF-κB and STAT3. FFAs, but not Cl-FFAs, up-regulated CCL2 and P-selectin in acinar cells. We conclude that FFAs are capable of up-regulating inflammatory mediators in pancreatic acini and given that they are highly produced during AP, mainly may contribute to the inflammatory response triggered in acinar cells by fat necrosis. No role is played by Cl-FFAs generated as a result of neutrophil infiltration.

Characterization and Outcomes in Patients Treated With Apremilast in Routine Clinical Practice in Spain: Results From the APPRECIATE Study. / Caracterización y resultados de pacientes tratados con apremilast en la práctica clínica habitual española: resultados del estudio APPRECIATE.

BACKGROUND AND OBJECTIVES: It is necessary to expand the knowledge in the use of apremilast in clinical practice. The APPRECIATE study (NCT02740218) aims to describe the characteristics of patients with psoriasis treated with apremilast, to evaluate their perspectives and those of dermatologists, as well as the outcomes obtained in clinical practice in Spain. METHODS: Observational, retrospective, cross-sectional, multicenter study of patients with chronic plaque psoriasis who could be contacted 6 (±1) months after apremilast initiation. The data were obtained from medical records and questionnaires from patients and physicians. RESULTS: A total of 80 patients were evaluated; at apremilast onset, they showed mean (standard deviation, SD) Psoriasis Area and Severity Index (PASI) = 8.3 (5.3), mean (SD) Dermatology Life Quality Index (DLQI) = 8.9 (6.6). At six months, 58.8% (n=47) of patients continued apremilast treatment (discontinuations due to lack of efficacy [16.3%], safety/tolerability [20.0%]). In patients continuing treatment, PASI75 was achieved by 36.7% of patients; mean (95% CI) DLQI score was 2.2 (0.7-3.6) and mean (SD) Patient Benefit Index score was 2.8 (0.8). Compliance with physicians' expectations was correlated with benefits reported by patients (r=0.636). Adverse events were reported by 56.3% of patients (the most common were diarrhoea and nausea). CONCLUSIONS: Patients receiving apremilast for 6 months in Spanish clinical practice, reported substantial improvements in their quality of life (mean DLQI reduced by more than 6 points) and disease severity (PASI75 achieved by over one-third of patients), despite less skin involvement than patients who enrolled in clinical trials.

Reticular variant of mid-dermal elastolysis after insertion of a pacemaker.

Summary Mid-dermal elastolysis is an unusual process characterized by the absence of the elastic fibres within the mid-dermis. The disappearance of these fibres causes fine wrinkles (type 1) or perifollicular protrusions (type 2) affecting the trunk, neck and arms. There is a female predilection, and most patients have a history of intense sun exposure. Recently, some cases of mid-dermal elastolysis presenting as reticular erythema have been reported. We report a case of reticular erythema with mid-dermal elastolysis that occurred in a 70-year-old man after insertion of a pacemaker.

The First Year of the AEVD Primary Cutaneous Lymphoma Registry. / Registro de linfomas cutáneos primarios de la AEDV: primer año de funcionamiento.

BACKGROUND AND OBJECTIVE: Primary cutaneous lymphomas are uncommon. This article describes the Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV) and reports on the results from the first year. PATIENTS AND METHODS: Disease registry for patients with primary cutaneous lymphoma. The participating hospitals prospectively recorded data on diagnosis, treatment, tests, and disease stage for all patients with primary cutaneous lymphoma. A descriptive analysis was performed. RESULTS: In December 2017, the registry contained data on 639 patients (60% male) from 16 university hospitals. The most common diagnoses, in order of frequency, were mycosis fungoides/Sézary syndrome (MF/SS) (348 cases, 55%), primary cutaneous B-cell lymphoma (CBCL) (184 cases, 29%), primary cutaneous CD30+ T-cell lymphoproliferative disorder (CD30+ CLPD) (70 cases, 11%), and other types of T-cell lymphoma (37 cases, 5%). In total, 105 (16.5%) of the cases recorded were incident cases. The most common diagnosis in the MF/SS group was classic MF (77.3%). Half of the patients with MF had stage IA disease when diagnosed, and the majority were either in partial remission (32.5%) or had stable disease (33.1%). The most widely used treatments were topical corticosteroids (90.8%) and phototherapy. The most common form of primary CBCL was marginal zone lymphoma (50%). Almost all of the patients had cutaneous involvement only and nearly half had stage T1a disease. Most (76.1%) were in complete remission. The main treatments were surgery (55.4%) and radiotherapy (41.9%). The most common diagnosis in patients with CD30+ CLPD was lymphomatoid papulosis (68.8%). Most of the patients (31.4%) had stage T3b disease and half were in complete remission. The most common treatments were topical corticosteroids (68.8%) and systemic chemotherapy (32.9%). CONCLUSION: The characteristics of patients with primary cutaneous lymphoma in Spain do not differ from those described in other series in the literature. The registry will facilitate clinical research by the AEDV's lymphoma group.

Cross-talk between TLR4 and PPARγ pathways in the arachidonic acid-induced inflammatory response in pancreatic acini.

Arachidonic acid (AA) is generally associated with inflammation in different settings. We assess the molecular mechanisms involved in the inflammatory response exerted by AA on pancreatic acini as an approach to acute pancreatitis (AP). Celecoxib (COX-2 inhibitor), TAK-242 (TLR4 inhibitor) and 15d-PGJ2 (PPARγ agonist) were used to ascertain the signaling pathways. In addition, we examine the effects of TAK-242 and 15d-PGJ2 on AP induced in rats by bile-pancreatic duct obstruction (BPDO). To carry out in vitro studies, acini were isolated from pancreas of control rats. Generation of PGE2 and TXB2, activation of pro-inflammatory pathways (MAPKs, NF-κB, and JAK/STAT3) and overexpression of CCL2 and P-selectin was found in AA-treated acini. In addition, AA up-regulated TLR4 and down-regulated PPARγ expression. Celecoxib prevented the up-regulation of CCL2 and P-selectin but did not show any effect on the AA-mediated changes in TLR4 and PPARγ expression. TAK-242, reduced the generation of AA metabolites and repressed both the cascade of pro-inflammatory events which led to CCL2 and P-selectin overexpression as well as the AA-induced PPARγ down-regulation. Thus, TLR4 acts as upstream activating pro-inflammatory and inhibiting anti-inflammatory pathways. 15d-PGJ2 down-regulated TLR4 expression and hence prevented the synthesis of AA metabolites and the inflammatory response mediated by them. Reciprocal negative cross-talk between TLR4 and PPARγ pathways is evidenced. In vivo experiments showed that TAK-242 and 15d-PGJ2 treatments reduced the inflammatory response in BPDO-induced AP. We conclude that through TLR4-dependent mechanisms, AA up-regulated CCL2 and P-selectin in pancreatic acini, partly mediated by the generation of PGE2 and TXB2, which activated pro-inflammatory pathways, but also directly by down-regulating PPARγ expression with anti-inflammatory activity. In vitro and in vivo studies support the role of TLR4 in AP and the use of TLR4 inhibitors and PPARγ agonists in AP treatment.

Engraftment syndrome and survival after respiratory failure post-bone marrow transplantation.

Respiratory failure (RF) requiring mechanical ventilation (MV) is a frequent, critical complication of bone marrow transplantation. RF has a global survival rate at 6 months of between 2 and 5%, depending on the patient group. Recently, a type of RF associated with hemoperipheric recovery has been described. This is known as engraftment syndrome. We have documented two cases of RF that follow the engraftment syndrome criteria and needed MV. Both patients had all the features identified for a bad prognosis described in the literature. Both are alive after being discharged from the hospital 20 months ago.

[Congenital obstructive disease of the ureter]. / Enfermedad obstructiva congénita del uréter.

Congenital diseases of the ureter form a broad sub-section of urology, where nomenclature is not clear and much less their etiopathogeny. In attempt to clear this up, we present the morphological study of ureteral development throughout the whole embryonic period, in both human and rat embryos, by means of the use of optical and electronic microscopy. After the description of ureteral obstruction phenomena (at the ureterovesical union and in the ureter itself), we discuss their physiopathological implications in embryonic development and we put forward a common etiopathogenic theory for obstructive diseases of the ureter with a congenital origin.

Lack of detection of Middle East respiratory syndrome coronavirus in mild and severe respiratory infections in Catalonia, northeastern Spain.

Surveillance of Middle East respiratory syndrome coronavirus (MERS-CoV) was conducted to explore the possible introduction and circulation of this novel virus in Catalonia, northeastern Spain. Five hundred and sixty-three samples from mild and severe respiratory infections collected between January 2012 and April 2013 were screened using real-time RT-PCR. All samples were negative, suggesting that MERS-CoV is not circulating silently in Catalonia.

Intravascular lymphoma in a patient with systemic lupus erythematosus: a case report.

Intravascular lymphoma IVL is a rare and aggressive disorder characterized by proliferation of large lymphoid cells (most commonly B-cells) within the lumen of small vessels of nearly every organ. Obliteration of vessels leads to the different clinical signs, being cutaneous lesions and neurological signs the most frequent presentations, whereas lymph node and reticuloendothelial system involvement is typically absent. No association with SLE has been described up to the present. We report a case of IVL in a patient with systemic lupus erythematosus (SLE) involving skin, central nervous system (CNS) and bone marrow.

Human embryo (12 mm) with mesohydronephrosis and ureterohydronephrosis.

This report describes a human embryo with a length of 12 mm (horizon XVII Streeterm 35 +/- 1 day old), in which the following malformations appear: Dilation on both sides of the Wolffian ducts, and the more caudal mesonephritic glomerules (mesohydronephrosis). Dilatation of both ureters and renal pelvis (uretero-hydronephrosis). These malformations are the result of the accumulation of liquid secreted by the mesonephros in a cloaca which is dilated, unwalled and blocked by an epithelial plug which is continuous with the cloacal membrane.

Development and Validation of a Mathematical Model for HTST Processing of Foods Containing Large Particles.

A mathematical treatment for a heat penetration phenomenon with variable boundary conditions is presented. The system of differential equations for determining the unsteady-state temperature distribution inside a particle was solved by use of spectral methods as a new tool in food process development. A preliminary study was conducted on the use of a mathematical model to predict lethality in a sterilizing process. The model was validated using a calibrated time-temperature integrator (TTI) with immobilized Bacillus stearothermophilus spores, commonly used in TTIs for process validation. A comparison between the experimental data using Bacillus stearothermophilus and the predicted data obtained with the proposed model showed good agreement.

[The first stages of the appendix development in the human embryo]. / Les premières phases de développement de l'appendice vermiforme chez l'embryon humain.

The cecoappendicular area of 14 human embryos with a length ranging from 6 to 17 mm from vertex to coccyx (28 to 48 days old; Carnegie stages 13 to 19) was studied. The appendix is not an atrophic remain of the caecum, it develops at the same time as the caecum. The first morphological anlage of the organ is observed in human embryos from 6 to 10 mm (28 to 37 days of age; Carnegie stages 13 to 16) in the form of an elevation covered with coelomic epithelium, constituted by the mesenchyme which surrounds the anlage of the caecum. In later stages, on human embryos of 11 to 16 mm (37 to 44 days of age; Carnegie stages 16 to 18), the mesoblastic anlage of the appendix is more evident, but it is not invaded by the entoblastic cells which come from the caecum on embryos of 12 to 13 mm. On embryos of about 17 mm (48 days old; Carnegie stage 19) the entoblastic anlage of the appendix has invaded the original mesoblastic anlage. The formation of the appendix by two anlage one earlier, mesoblastic, and another later, entoblastic, is similar to that of other lymphoid organs like the sack of Fabricius in birds.

Contribution to the study of the development of the terminal portion of the Wolffian duct and the ureter.

Ten human embryos ranging from 10 to 20 mm in vertex-coccyx length (Horizons XVI and XVII Streeter) aged between 33 +/- 1 and 39 +/- 1 days, were studied in order to interpret the mechanism which determines the displacement of the ureter from the dorsal part of the Wolffian duct toward the lateral wall of the bladder. We demonstrated that this movement occurs due to the fact that the duct common to the ureter and the Wolffian duct undergoes a process of internal rotation before it is absorbed by the urogenital sinus. This determines that the ureteral orifice enter the urogenital sinus laterally with respect to the Wolffian duct. This absorption indicates that the mucosa of the trigone is of mesoblastic origin and the remainder of the besical of endoblastic origin. The origin of the muscular apparatus of the detrusor is entirely mesoblastic.

Obstruction and normal recanalization of the ureter in the human embryo. Its relation to congenital ureteric obstruction.

In this work, after the study of 45 normal human embryos of 5-55 mm from vertex to coccyx, it is shown that the ureteric ducts, which in the first phases of development are permeable (embryos of 5-13 mm), constantly undergo a process of obstruction and posterior recanalization of their lumen, which takes place when they are from 14 to 22 mm. These processes begin in the middle zone of the ureters and progress proximally and distally until they cover its entire length, for which these ducts, which in embryos of approximately 17 mm in length form solid cords, but in the embryos of 23 mm are totally permeable. This obstructive process is found in relation to atrophy and loss of activity of the mesonephros, while that of recanalization follows the intense longitudinal growth of the ureters in this phase of development. These modifications, which the ureteric lumen normally undergoes during its embryonic development, are of great importance for correct interpretation of the pathogenic mechanism of congenital ureteric strictures and valves.