Pityriasis Rubra Pilaris: A Multicentric Case Series of 65 Spanish Patients.

INTRODUCTION: PRP is a rare entity of unknown etiopathogenesis. Lack of management guidelines makes it a challenge for clinicians. OBJECTIVE: To add our experience to increase evidence about PRP. METHODS: We performed a retrospective, descriptive and multicentric study of 65 patients with PRP, being the largest European case series of patients with PRP. RESULTS: PRP was more frequent in male patients with an average age of 51 years, but erythrodermic forms presented in older patients (average age 61 years). Six (75%) paediatric patients and ten (60%) non-erythrodermic adults controlled their disease with topical corticosteroids. On the contrary, 26 (68%) erythrodermic patients required biologic therapy as last and effective therapy line requiring an average of 6.5 months to achieve complete response. CONCLUSION: Our study showed a statistical difference in terms of outcome and response to treatment between children or patients with limited disease and patients who develop erythroderma.

Bipolar seesaw control on last interglacial sea level.

Our current understanding of ocean-atmosphere-cryosphere interactions at ice-age terminations relies largely on assessments of the most recent (last) glacial-interglacial transition, Termination I (T-I). But the extent to which T-I is representative of previous terminations remains unclear. Testing the consistency of termination processes requires comparison of time series of critical climate parameters with detailed absolute and relative age control. However, such age control has been lacking for even the penultimate glacial termination (T-II), which culminated in a sea-level highstand during the last interglacial period that was several metres above present. Here we show that Heinrich Stadial 11 (HS11), a prominent North Atlantic cold episode, occurred between 135 ± 1 and 130 ± 2 thousand years ago and was linked with rapid sea-level rise during T-II. Our conclusions are based on new and existing data for T-II and the last interglacial that we collate onto a single, radiometrically constrained chronology. The HS11 cold episode punctuated T-II and coincided directly with a major deglacial meltwater pulse, which predominantly entered the North Atlantic Ocean and accounted for about 70 per cent of the glacial-interglacial sea-level rise. We conclude that, possibly in response to stronger insolation and CO2 forcing earlier in T-II, the relationship between climate and ice-volume changes differed fundamentally from that of T-I. In T-I, the major sea-level rise clearly post-dates Heinrich Stadial 1. We also find that HS11 coincided with sustained Antarctic warming, probably through a bipolar seesaw temperature response, and propose that this heat gain at high southern latitudes promoted Antarctic ice-sheet melting that fuelled the last interglacial sea-level peak.

Subclinical enthesopathy of extensor digitorum tendon is highly prevalent and associated with clinical and ultrasound alterations of the adjacent fingernails in patients with psoriatic disease.

BACKGROUND: Nail psoriasis disease is associated with an increased probability of psoriatic arthritis, and its clinical signs may have different correlates with the pathogenesis of adjacent bone destruction and have different prognostic value. Recent publications about psoriasis and nail psoriatic disease describe different ultrasonographic findings but the relationship between these ungueal alterations measured by ultrasonography and the presence of enthesopathy of the extensor digitorum has yet to be discovered. OBJECTIVE: To describe which ultrasonographic characteristics of nail psoriasis are associated with the presence of subclinical enthesopathy in patients with PsO and asymptomatic PsA. METHODS: Patients with psoriasis and asymptomatic psoriatic arthritis were included in the prospective study. Demographic, clinical data and PASI and NAPSI indexes were recorded of all the patients in the assessment visit. The US assessment included Achilles tendon, extensor digitorum tendon and US scan of the nail plate, nail matrix, nail bed and adjacent skin over nail matrix of the five nails of each hand. RESULTS: Forty-eight patients were included in the study; 33 of them presented ultrasound evidence of extensor digitorum tendon enthesopathy. Nails of the patients with subclinical enthesopathy had a higher NAPSI and skin thickness than the nails of the patients without subclinical enthesopathy (P = 0.047). Patients with asymptomatic enthesopathy had significantly thicker proximal nail folds (1.44 ± 0.312 vs. 1.23 ± 0.27, P = 0.023). Nail beds and matrices were also thicker but the differences were not statistically significant (1.77 ± 0.27 vs. 1.74 ± 0.21, P = 0.66, and 1.79 ± 0.28 vs. 1.67 ± 0.19, P = 0.10, respectively). No statistically significant differences in the trilaminar structure were found between both groups. Patients with and without asymptomatic enthesopathy of extensor digitorum tendons did not statistically differ as regards ultrasonographic alterations of the Achilles tendons (60.6% vs. 46.4%, P 0.368). CONCLUSION: Enthesopathy abnormalities can be detected by US in patients with psoriasis without musculoskeletal complaints frequently. There is a close relationship between subclinical enthesopathy of the extensor digitorum tendon and the presence of nail alterations. Further studies are required to research what implications have the presence of these ungual alterations measured by US, and how it affects later development of a PsA.

Balanced secretion of anti-CEA × anti-CD3 diabody chains using the 2A self-cleaving peptide maximizes diabody assembly and tumor-specific cytotoxicity.

Adoptive transfer of genetically engineered human cells secreting bispecific T-cell engagers has shown encouraging therapeutic effects in preclinical models of cancer. However, reducing the toxicity and improving the effectiveness of this emerging immunotherapeutic strategy will be critical to its successful application. We have demonstrated that for gene-based bispecific antibody strategies, two-chain diabodies have a better safety profile than single-chain tandem scFvs (single-chain variable fragments), because their reduced tendency to form aggregates reduces the risk of inducing antigen-independent T-cell activation. Here, we demonstrate that the incorporation of a 2A self-processing peptide derived from foot-and-mouth disease virus conveying co-translational cleavage into a two-chain anti-CD3 × anti-CEA diabody gene enables near-equimolar expression of diabody chains 1 and 2, and thus increases the final amount of assembled diabody. This was found to maximize diabody-mediated T-cell activation and cytotoxicity against carcinoembryonic antigen-positive tumor cells.

Infantile hemangiomas with minimal or arrested growth associated with soft tissue hypertrophy: a case series of 10 patients.

BACKGROUND: Infantile hemangiomas with minimal or arrested growth (IH-MAGs) are characterized by a proliferative component of <25% of its surface area. The co-occurrence of IH-MAGs and soft tissue anomalies is rare, and case series of this association are lacking. OBJECTIVE: We present 10 cases of IH-MAGs associated with soft tissue hypertrophy and describe their clinical features. METHODS: We reviewed all infantile hemangiomas with minimal or arrested growth seen between 2009 and 2016 in the dermatology clinic department at Hospital Santa Creu i Sant Pau, Barcelona. To collect more patients, we also requested cases from the Hemangioma Investigator Group and members of the Spanish Society of Vascular Anomalies. RESULTS: Ten patients had IH-MAGs associated with soft tissue hypertrophy; seven involving the arm and three involving the leg. All displayed a segmental pattern, a doughy and puffy texture and prominent surface veins. No significant asymmetries in limbs and no other visceral anomalies were observed at follow-up (range 15 months to 7 years). One patient reported coldness in the limb with infantile hemangioma, but RMI-angiography did not disclose a vascular malformation underneath the lesion. Ulceration was observed in three patients. The proliferative component in all IH-MAGs had faded at 1-year follow-up, while soft tissue hypertrophy and prominent vessels remained unchanged. CONCLUSIONS: In this first case series of IH-MAGS associated with soft tissue hypertrophy, soft tissue hypertrophy was not progressive and remained unchanged over time, unlike the proliferative component of classic infantile hemangioma. The origin of the prominent vessels and the higher ulceration risk are unknown; however, these findings are probably related to a minor disruption of local vessels not detected in imaging tests.

[Gastrointestinal tract volvulus: diagnosis and correlation between plain-film X-ray and multidetector computed tomography findings]. / Vólvulos del tracto gastrointestinal. Diagnóstico y correlación entre radiología simple y tomografía computarizada multidetector.

Gastrointestinal volvuli cause processes that manifest as acute abdomen. Volvuli are important not because they are common, but rather because their possible complications can be severe. All types of volvuli share a common pathophysiology, which consists of intestinal obstruction in a closed loop that results in ischemia. The clinical manifestations are nonspecific, so radiologists play a very important role in the early identification of the most common signs of torsion. These include the "bird's beak sign", the "whirlpool sign", and signs of potentially reversible or irreversible ischemia. The treatment of choice in most cases is surgery, either to correct the torsion and save the organ or to resect it if it is necrotic.

Agreement between central corneal thickness measured using Pentacam, ultrasound pachymetry, specular microscopy and optic biometer Lenstar LS 900 and the influence of intraocular pressure.

PURPOSE: To compare central corneal thickness (CCT) values obtained by Lenstar (LE), Pentacam (PC), specular microscopy (SM) and ultrasound pachymetry (UP) in healthy corneas and study their influence on intraocular pressure (IOP) readings determined by Goldmann applanation tonometry (GAT). METHODS: CCT was measured in 76 healthy subjects by LE, PC, SM and UP. We established Lin's concordance correlation coefficient (ρ-C) between different techniques. The influence of CCT on GAT was established through univariate linear regression models, IOP being the dependent variable. RESULTS: The highest ρ-C was found between LE and SM at 0.94 (95% CI: 0.91-0.96) and between LE and UP at 0.95 (95% CI: 0.94-0.97). IOP readings showed less variability when CCT was determined using LE (7.7%, B = 0.16; 95% CI: 0.004-0.28). CONCLUSIONS: Although CCT values obtained with UP, PC, SM and LE show good correlation, these methods are not completely interchangeable. The amount of IOP variation differs when CCT is determined using LE or SM.

Evidence-based guidelines of the spanish psoriasis group on the use of biologic therapy in patients with psoriasis in difficult-to-treat sites (nails, scalp, palms, and soles).

Psoriatic lesions affecting the scalp, nails, palms, and the soles of the feet are described as difficult-to-treat psoriasis and require specific management. Involvement of these sites often has a significant physical and emotional impact on the patient and the lesions are difficult to control with topical treatments owing to inadequate penetration of active ingredients and the poor cosmetic characteristics of the vehicles used. Consequently, when difficult-to-treat sites are involved, psoriasis can be considered severe even though the lesions are not extensive. Scant information is available about the use of biologic therapy in this setting, and published data generally comes from clinical trials of patients who also had moderate to severe extensive lesions or from small case series and isolated case reports. In this article we review the quality of the scientific evidence for the 4 biologic agents currently available in Spain (infliximab, etanercept, adalimumab, and ustekinumab) and report level i evidence for the use of biologics to treat nail psoriasis (level of recommendation A) and a somewhat lower level of evidence in the case of scalp involvement and palmoplantar psoriasis.

Detection and characterisation of visual field defects using Octopus perimetry in congenital glaucoma.

PURPOSE: To detect and characterise visual field (VF) defects using static Octopus perimetry in patients with primary congenital glaucoma (PCG) and to determine VF quality and time duration. MATERIAL AND METHODS: Eighty-eight eyes of 70 patients diagnosed with PCG were included. Assessments were performed using an Octopus 900 and each eye was assessed with the tendency-oriented perimetry (G-TOP) algorithm. Quantitative VF data were collected: quality data (false positive and negative response, and time duration) and results of mean deviation (MD) and square root of loss variance (sLV). Qualitative data were collected: the presence of diffuse and localized defects, the affected hemifield and grade of defects using the Aulhorn and Karmeyer classification. Correlations between perimetric results and clinical variables were analysed. RESULTS: Median age was 11 (8-17) years. 65.9% (58/88) of PCG eyes showed VF defects. Diffuse defects were observed in 10/58 eyes (16.94%) (mean MD = 23.92 [SD: 2.52]) dB) and localized defects in 48/58 eyes (82.75%). The most frequent defect was spot-like/stroke-like/incipient paracentral scotoma (n = 15), nasal step (n = 8), adding arcuate defect (n = 2), half ring-shaped (n = 13) and concentric defect with a central island (n = 9). And the most frequent affected visual hemifield was inferior hemifield. Mean test duration was 2 min 12 s (SD: 21.6 s). MD and sLV values were correlated with best corrected visual acuity (BCVA), cup to disc ratio and number of antiglaucoma surgeries (all P < .001). CONCLUSION: A high number of diffuse and localized defects were identified using Octopus perimetry in PCG patients. The most frequent defect was paracentral scotoma and inferior hemifield was the most affected.

Congenital stromal corneal dystrophy in a Spanish family: Clinical, genetic and histological analysis.

PURPOSE: To present the clinical, genetic, and histopathological features of the ninth family affected by congenital stromal corneal dystrophy (CSCD) to date. METHODS: Twelve cases of a Spanish family affected by CSCD were analyzed regarding history, visual acuity (VA, decimal scale), an ophthalmologic exam and specular microscopy. Five eyes were treated by deep anterior lamellar keratoplasty (DALK), and thirteen eyes by penetrating keratoplasty (PK). In the two last generations, a genetic study was performed. RESULTS: Most of the patients affected were born with opaque corneas except for three, whose corneas were clear at birth. Biomicroscopy showed a whitish diffuse stromal opacity with an unaltered epithelium, causing poor VA (from hand motions to 0.4). Patients treated with PK presented mean postoperative VA of 0.19±0.20 over a follow-up time of 235.3±101.4months with 38% recurrences. Patients who underwent DALK experienced VA improvement to 0.17±0.11 over a follow-up time of 10.8±2.6months without signs of recurrence. In the latter, the big bubble technique was not achieved, so a manual technique was performed. The genetic study showed heterozygosis for a 1-bp deletion at nucleotide 962 in exon 8 of the decorin gene. CONCLUSIONS: CSCD is a rare entity, which should be treated by DALK whenever possible, obtaining better results than PK. Close monitoring of children of affected individuals is important, because CSCD can progress during the early years of life.

Corneal endothelial validation in the eye bank: differences in automated methods and repeatability.

PURPOSE: To evaluate reproducibility of endothelial cell density (ECD) measurements using the Konan Cell Check D in donor corneas by two different ophthalmologists and to compare the two automated cell count methods (center and flex-center) available in the software of this specular microscope. METHODS: ECD values were quantified in 54 donor corneas by two independent investigators using the Cell Check D (Konan Medical USA Inc) with both automated cell count methods. In the center method, at least 30 contiguous cells are marked. For the flex-center method, an area is delineated and only the cells within the designated area are counted. RESULTS: The mean ECD was 2473.81±378.22 cells/mm2. Good ECD intergrader reproducibility for the center (ICC=0.821) and the flex-center method (ICC=0.784) were noted. Poor reliability was observed for coefficient of variation and hexagonality (ICC≤0.265). When both methods for ECD analysis were compared, a moderate correlation for the two independent graders using the two manual (center and flex-center) methods was detected (correlation coefficient of 0.678 and 0.745 for each of the investigators). Comparison between methods yielded significantly higher ECD with the flex-center method (P=0.013). When corneas were divided by ECD, those under 2200 cells/mm2 and those between 2200 and 2700 cells/mm2 also had significantly higher ECD with the flex-center method (P<0.022). CONCLUSIONS: ECD values are reproducible with both methods, although the flex-center method ECDs tend to be higher, particularly in cases of low ECD. Eye banks and surgeons should exercise caution in making decisions based only on small differences in ECD.

Functional and expression analysis of the metal-inducible dmeRF system from Rhizobium leguminosarum bv. viciae.

A gene encoding a homolog to the cation diffusion facilitator protein DmeF from Cupriavidus metallidurans has been identified in the genome of Rhizobium leguminosarum UPM791. The R. leguminosarum dmeF gene is located downstream of an open reading frame (designated dmeR) encoding a protein homologous to the nickel- and cobalt-responsive transcriptional regulator RcnR from Escherichia coli. Analysis of gene expression showed that the R. leguminosarum dmeRF genes are organized as a transcriptional unit whose expression is strongly induced by nickel and cobalt ions, likely by alleviating the repressor activity of DmeR on dmeRF transcription. An R. leguminosarum dmeRF mutant strain displayed increased sensitivity to Co(II) and Ni(II), whereas no alterations of its resistance to Cd(II), Cu(II), or Zn(II) were observed. A decrease of symbiotic performance was observed when pea plants inoculated with an R. leguminosarum dmeRF deletion mutant strain were grown in the presence of high concentrations of nickel and cobalt. The same mutant induced significantly lower activity levels of NiFe hydrogenase in microaerobic cultures. These results indicate that the R. leguminosarum DmeRF system is a metal-responsive efflux mechanism acting as a key element for metal homeostasis in R. leguminosarum under free-living and symbiotic conditions. The presence of similar dmeRF gene clusters in other Rhizobiaceae suggests that the dmeRF system is a conserved mechanism for metal tolerance in legume endosymbiotic bacteria.

The axonal repellent Slit2 inhibits pericyte migration: potential implications in angiogenesis.

The Slit family of secreted proteins acts through the Roundabout (Robo) receptors to repel axonal migration during central nervous system development. Emerging evidence shows that Slit/Robo interactions also play a role in angiogenesis. The effect of Robo signaling on endothelial cells has been shown to be context-dependent. However, the role of Slit/Robo in pericytes has been largely unexplored. The aim of this study was to determine the effect of Slit2 on primary human pericytes and to address the underlying mechanisms, including the receptors potentially implicated. We demonstrate that both Robo1 and Robo4 are expressed by human pericytes. In the presence of their ligand Slit2, spontaneous and PDGF-induced migration of pericytes was impaired. This antimigratory activity of Slit-2 correlated with the inhibition of actin-based protrusive structures. Interestingly, human pericyte interaction with immobilized Slit2 was inhibited in the presence of anti-Robo1 and anti-Robo4 blocking antibodies, suggesting the implication of both receptors. These results add new insights into the role of Slit proteins during the angiogenic process that relies on the directional migration not only of endothelial cells but also of pericytes.

Analysis of the appropriateness of the clinical indications for neuroimaging studies.

OBJECTIVES: To determine the most common clinical indications for different diagnostic neuroimaging tests. To analyze the diagnostic yield for each type of test in function of its clinical indication. To quantify the number of additional imaging tests generated as a consequence of pathological findings on the initial study or of the physician's requesting an inappropriate study. MATERIAL AND METHODS: We reviewed the clinical indications and radiological report for computed tomography (CT) and magnetic resonance imaging (MRI) studies of the brain, head, and neck carried out during a 30-day period in three intermediate level hospitals with similar characteristics. We counted the studies with pathological findings and those with normal findings. We recorded cases that required additional imaging studies. RESULTS: CT and MRI studies of the brain are the most frequently requested neuroimaging studies. The most common indications for examinations requested from the neurology department were headache, head trauma, and acute neurological deficit. The most common indication for examinations requested from the ear, nose, and throat department was hearing loss. The percentage of examinations with pathological findings ranged from 6% to 71% depending on the clinical indication. Additional imaging studies were necessary in 3.5% of the cases. CONCLUSIONS: Most neuroimaging studies are performed for especially prevalent clinical indications; however, in many cases the degree of concordance between the clinical and radiological diagnosis shows there is much room for improvement.

Patients with severe polytrauma: management and imaging protocols.

Traumatic injuries can be severe and complex, requiring the coordinated efforts of a multidisciplinary team. Imaging tests play a fundamental role in rapid and accurate diagnosis. In particular, whole-body computed tomography (CT) has become a key tool. There are different CT protocols depending on the patient's condition; whereas dose-optimized protocols can be used in stable patients, time/precision protocols prioritizing speed at the cost of delivering higher doses of radiation should be used in more severe patients. In unstable patients who cannot be examined by CT, X-rays of the chest and pelvis and FAST or e-FAST ultrasound studies, although less sensitive than CT, enable the detection of situations that require immediate treatment. This article reviews the imaging techniques and CT protocols for the initial hospital workup for patients with multiple trauma.

Update on acute appendicitis: Typical and untypical findings.

Acute appendicitis is the most common indication for emergency abdominal surgery throughout the world and a common reason for consultation in emergency departments. In recent decades, diagnostic imaging has played a fundamental role in identifying acute appendicitis, helping to reduce the rate of blind laparotomies and hospital costs. Given the results of clinical trials supporting the use of antibiotic therapy over surgical treatment, radiologists need to know the diagnostic criteria for complicated acute appendicitis to be able to recommend the best treatment option. This review aims not only to define the diagnostic criteria for appendicitis in different imaging modalities (ultrasonography, computed tomography, and magnetic resonance imaging), but also to explain the diagnostic protocols, atypical presentations, and other conditions that can mimic appendicitis.

Method for quantifying arousal and consciousness in healthy states and severe brain injury via EEG-based measures of corticothalamic physiology.

BACKGROUND: Characterization of normal arousal states has been achieved by fitting predictions of corticothalamic neural field theory (NFT) to electroencephalographic (EEG) spectra to yield relevant physiological parameters. NEW METHOD: A prior fitting method is extended to distinguish conscious and unconscious states in healthy and brain injured subjects by identifying additional parameters and clusters in parameter space. RESULTS: Fits of NFT predictions to EEG spectra are used to estimate neurophysiological parameters in healthy and brain injured subjects. Spectra are used from healthy subjects in wake and sleep and from patients with unresponsive wakefulness syndrome, in a minimally conscious state (MCS), and emerged from MCS. Subjects cluster into three groups in parameter space: conscious healthy (wake and REM), sleep, and brain injured. These are distinguished by the difference X-Y between corticocortical (X) and corticothalamic (Y) feedbacks, and by mean neural response rates α and ß to incoming spikes. X-Y tracks consciousness in healthy individuals, with smaller values in wake/REM than sleep, but cannot distinguish between brain injuries. Parameters α and ß differentiate deep sleep from wake/REM and brain injury. COMPARISON WITH EXISTING METHODS: Other methods typically rely on laborious clinical assessment, manual EEG scoring, or evaluation of measures like Φ from integrated information theory, for which no efficient method exists. In contrast, the present method can be automated on a personal computer. CONCLUSION: The method provides a means to quantify consciousness and arousal in healthy and brain injured subjects, but does not distinguish subtypes of brain injury.

Recommendations on the use of computed tomography in the stroke code: Consensus document SENR, SERAU, GEECV-SEN, SERAM.

The Spanish Society of Emergency Radiology (SERAU), the Spanish Society of Neuroradiology (SENR), the Spanish Society of Neurology through its Cerebrovascular Diseases Study Group (GEECV-SEN) and the Spanish Society of Medical Radiology (SERAM) have met to draft this consensus document that will review the use of computed tomography in the stroke code patients, focusing on its indications, the technique for its correct acquisition and the possible interpretation mistakes.

Non-hematopoietic stem cells as factories for in vivo therapeutic protein production.

As an alternative to recombinant protein administration, ex vivo gene-modified cells may provide a novel strategy for systemic delivery of therapeutic proteins. This approach has been used in preclinical and clinical studies of a plethora of pathological conditions, including anemia, hemophilia and cancer for the production of erythropoietin, coagulation factors, immunostimulatory cytokines, recombinant antibodies and angiogenesis inhibitors. Cell delivery vehicles may also be varied: autologous or allogeneic, precursor or terminally differentiated cells, with targeting properties or immobilized in immunoprotective devices. This field did not meet the expectation raised initially, mainly because of difficulties with obtaining therapeutic plasma levels and the short lifespan of producer cells that hampered clinical application. Different non-hematopoietic stem/progenitor cells have emerged as potential delivery vehicles, since they are easy to obtain, expand and transduce, and they exhibit prolonged lifespans (with mesenchymal stem cells probably being the most popular cell type, but not the only one). Special emphasis is placed on the different routes used to deliver these cellular vehicles and the controversies about their targeting abilities.