Pruritus Intensity Scales across Europe: a prospective validation study.

BACKGROUND: Chronic pruritus (CP) is a subjective symptom, and it is necessary to assess its intensity with validated patient-reported outcome tools in order to allow determination of the treatment course. OBJECTIVES: So far, the itch intensity scales were validated in small cohorts and in single languages. Here, we report the validation of the numerical rating scale, the verbal rating scale and the visual analogue scale for the worst and average pruritus intensity in the last 24h in several languages across Europe and across different pruritic dermatoses. METHODS: After professional translation, the intensity scales were digitized for use as a tablet computer application. Validation was performed in clinics for Dermatology in Austria, France, Germany, Italy, Poland, Russia, Spain, Switzerland and Turkey. RESULTS: A total of 547 patients with contact dermatitis, chronic nodular prurigo, psoriasis vulgaris, lichen planus or cutaneous T-cell lymphoma were included. The intensity scales showed a high level of reproducibility and inter-correlations with each other. The correlation with the Dermatology Life Quality Index was weak to strong in nearly all countries and dermatoses with the exception of France and patients with chronic nodular prurigo, for which no statistically significant correlations were found. CONCLUSIONS: The numerical rating scale, the verbal rating scale und the visual analogue scales are valid instruments with good reproducibility and internal consistency in German (Germany, Austria, Switzerland), French, Italian, Polish, Russian, Spanish and Turkish for different pruritic dermatoses. VAS worst was the best reproducible and consistent measuring instrument in all countries.

Cross-European validation of the ItchyQoL in pruritic dermatoses.

BACKGROUND: Chronic pruritus (CP) is a frequently occurring symptom in inflammatory dermatoses, causing a high burden and limitations to health-related quality of life (HRQoL). OBJECTIVE: The ItchyQoL was developed to assess the impairment to HRQoL in patients with CP. However, it has only been validated in English and German. Here, we report the validation in several languages across Europe. METHODS: After professional translation, the versions of ItchyQoL were digitized for use as a tablet application. Validation was performed in clinics for dermatology in Austria, France, Germany, Italy, Poland, Russia, Spain, Switzerland and Turkey. RESULTS: Five hundred and thirty-five patients with either contact dermatitis, chronic prurigo - nodular type, psoriasis vulgaris, lichen planus or mycosis fungoides/Sézary syndrome and with CP ≥ 3 on the numerical rating scale were included. ItchyQoL showed a high level of consistency (Cronbach's-α, all: 0.95) and test-retest reliability (intraclass correlation: 0.91). It strongly correlated with the Dermatology Life Quality Index (r = 0.72, P < 0.001) and moderately correlated with itch intensity scales in the study population (visual analogue scale r = 0.46; numerical rating scale r = 0.51; verbal rating scale r = 0.51, for all: P < 0.001). CONCLUSION: ItchyQoL is now also validated in French, Italian, Polish, Russian, Spanish and Turkish and can be used in clinical trials in countries speaking these languages.

European academy of dermatology and venereology European prurigo project: expert consensus on the definition, classification and terminology of chronic prurigo.

BACKGROUND: The term prurigo has been used for many decades in dermatology without clear definition, and currently used terminology of prurigo is inconsistent and confusing. Especially, itch-related prurigo remains unexplored regarding the epidemiology, clinical profile, natural course, underlying causes, available treatments and economic burden, although burdensome and difficult to treat. OBJECTIVE: To address these issues, the multicentre European Prurigo Project (EPP) was designed to increase knowledge on chronic prurigo (CPG). In the first step, European experts of the EADV Task Force Pruritus (TFP) aimed to achieve a consensus on the definition, classification and terminology of CPG. Additionally, procedures of the cross-sectional EPP were discussed and agreed upon. METHODS: Discussions and surveys between members of the TFP served as basis for a consensus conference. Using the Delphi method, consensus was defined as an agreement ≥75% among the present members. RESULTS: Twenty-four members of the TFP participated in the consensus conference. Experts consented that CPG should be used as an umbrella term for the range of clinical manifestations (e.g. papular, nodular, plaque or umbilicated types). CPG is considered a distinct disease defined by the presence of chronic pruritus for ≥6 weeks, history and/or signs of repeated scratching and multiple localized/generalized pruriginous skin lesions (whitish or pink papules, nodules and/or plaques). CPG occurs due to a neuronal sensitization to itch and the development of an itch-scratch cycle. CONCLUSION: This new definition and terminology of CPG should be implemented in dermatology to harmonize communication in the clinical routine, clinical trials and scientific literature. Acute/subacute forms of prurigo are separated entities, which need to be differentiated from CPG and will be discussed in a next step. In the near future, the cross-sectional EPP will provide relevant clinical data on various aspects of CPG leading to new directions in the scientific investigation of CGP.

Intracranial stents in the endovascular treatment of acute ischemic stroke. / Uso del stent intracraneal en el tratamiento endovascular en agudo del ictus.

OBJECTIVE: To evaluate the efficacy and safety of intracranial stenting as a rescue therapy after failed mechanical thrombectomy in patients with acute ischemic stroke. MATERIAL AND METHODS: We retrospectively studied 42 patients treated with intracranial stenting after failed mechanical thrombectomy between December 2008 and January 2016. We compared outcomes before and after the incorporation of stentrievers. We assessed the degree of recanalization in the carotid and basilar territories (modified TIMI score), prognostic factors, and outcome (modified Rankin Score at 3 months). Safety was evaluated in function of the appearance of symptomatic intracranial hemorrhage (SICH). RESULTS: Median NIHSS was 17 in patients with carotid territory strokes and 26 in those with vertebrobasilar territory strokes. Median time from onset of symptoms to treatment was 225minutes in carotid territory strokes and 390minutes in vertebrobasilar territory strokes. A total of 10 patients underwent intravenous fibrinolytic therapy before treatment with stentrievers. Two patients developed SICH; both had undergone intravenous fibrinolytic therapy (p=0.0523). Recanalization was effective in 30 (71.4%) in the entire series: in 7 (50%) of 14 patients treated before the incorporation of stentrievers and in 23 (82.1%) of 28 treated after the incorporation of stentrievers (p=0.0666). Outcome at 3 months was good in 2 (14.3%) patients in the earlier group and in 14 (50%) patients in the later group (p=0.042). We found significant associations between recanalization and outcome (p=0.0415) and between shorter time to treatment and outcome (p=0.002). Outcome was good in 14 (48.3%) of the 29 patients with carotid territory strokes and in 2 (15.4%) of the 13 patients with vertebrobasilar territory strokes (p=0.078). CONCLUSIONS: Intracranial stenting is the rescue treatment when the usual treatment fails. Stentrievers must be used to eliminate the clot burden before stenting. In our study, antiplatelet treatment did not seem to increase the risk of SICH except in patients with prior intravenous fibrinolytic treatment.

European EADV network on assessment of severity and burden of Pruritus (PruNet): first meeting on outcome tools.

BACKGROUND: Chronic pruritus is a frequently occurring symptom of various dermatoses that causes a high burden and impaired quality of life. An effective anti pruritic therapy is important for the patient, but its effectiveness is difficult to evaluate. Diverse methods and interpretations of pruritic metrics are utilized in clinical trials and the daily clinical practice in different countries, resulting in difficulties comparing collected data. METHODS: We founded a European Network on Assessment of Severity and Burden of Pruritus (PruNet) that is supported by the EADV. PruNet consists of 28 experts from 15 EU countries (21 dermatologists, 5 medical informaticists, 2 psychologists) and aims to unify the assessment of itch in routine dermatological care. Following a preliminary survey, a consensus conference was held in order to agree upon the prioritization of patient-reported outcome tools. RESULTS: Through utilizing the Delphi method, it was agreed that tools for measuring itch intensity (ex. the visual analogue scale) and quality of life (ex. ItchyQoL) are of primary importance and should urgently be foremost validated. CONCLUSION: The validation and harmonization of standards are needed for the improvement of quality care for patients suffering from pruritic dermatoses. This summer, the first validation studies in several EADV member countries already began.

First-Pass Effect in M1-Occlusion Stroke Patients Treated with Combined Stent-Retriever/Large-Bore Distal Aspiration Catheter Thrombectomy.

INTRODUCTION: Combined stent-retriever/large-bore distal aspiration catheter (LB-DAC) thrombectomy was recently introduced to treat large-vessel occlusion; however, it is unclear whether larger inner diameters improve outcomes. We compared angiographic and clinical outcomes in patients with occlusions of the M1 segment of the middle cerebral artery treated with mechanical thrombectomy using extra-LB-DAC versus LB-DAC in combination with stent-retrievers. METHODS: We analyzed consecutive patients with M1 occlusion included in the ROSSETTI registry treated with non-balloon guide catheter combined LB-DAC/stent-retriever thrombectomy between June 2019 and April 2022. We compared demographics, baseline clinical variables, procedural variables, angiographic outcomes, and clinical outcomes [National Institute of Health Stroke Scale score at 24 h (24h-NIHSS) and modified Rankin scale score at 3 months] between patients treated with extra-LB-DAC (Sofia Plus, MIVI Q6, Catalyst7; inner diameter, 0.068″-0.070″) versus LB-DAC (Sofia 5F, MIVI Q5, Catalyst 6; inner diameter, 0.055″-0.064″). Primary outcome was the first-pass effect (FPE) rate, defined as near-complete/complete reperfusion (mTICI 2c-3) after a single pass of the device. RESULTS: We included 324 patients (extra-LB-DAC, 185, 57.1% patients). Demographics, clinical data, and clinical outcomes were similar between the two groups; however, there was a trend towards improvement in National Institute of Health Stroke Scale score at 24 h (24h-NIHSS) in the cohort treated with extra-LB-DAC 9 points (IQR 4;16 points) vs. 12 points (IQR 4;18 points, P = 0.083). Patients treated with extra-LB-DAC had higher FPE rate (47% vs. 30.9%; P = 0.003) and higher modified FPE (mTICI ≥ 2b after a single pass) rate (65.9% vs 46.8%; P = 0.001). The use of extra-LB-DAC was an independent factor in predicting FPE (odds ratio 1.982, 95% confidence interval 1.250-3.143, P = 0.004). CONCLUSION: Our results suggest that in combined LB-DAC/stent-retriever thrombectomy, a larger aspiration catheter inner diameter is associated with higher rates of FPE and mFPE.

Incidence, prognosis, and prediction of haemorrhagic transformation after revascularisation for stroke.

INTRODUCTION: Haemorrhagic transformation is a major complication of acute ischaemic stroke (AIS). We sought to determine the predictors and clinical impact of intracranial haemorrhage (ICH) after revascularisation therapy. METHODS: We conducted a retrospective, single-centre study including 235 patients with AIS who underwent intravenous recombinant tissue plasminogen activator (IV-rtPA) therapy and/or endovascular treatment. A binary logistic regression model was used to determine the variables associated with ICH, parenchymal haematomas (PH), modified Rankin Scale (mRS) scores, and mortality. RESULTS: ICH was detected in 57 (30 with PH) of 183 patients included. Mechanical thrombectomy, either alone (OR 3.3 [1.42-7.63], P=.005) or in combination with IV-rtPA (OR 3.39 [1.52-7.56], P=.003), was associated with higher risk of ICH, while higher Alberta Stroke Program Early CT scores (OR 0.71 [0.55-0.91], P=.007) were associated with lower risk. Patients with older age (OR 1.07 [1.02-1.13], P=.006) and occlusion of the terminal branch of the internal carotid artery (OR 4.03 [1.35-11.99], P=.012) had a higher risk of PH, while the use of IV-rtPA alone (OR 0.24 [0.08-0.68], P=.008) was associated with lower risk of PH. Only PH was associated with disability as measured by the mRS (OR 3.2 [1.17-8.76], P=.02) and higher mortality (OR 5.06 [1.65-15.5], P=.005). CONCLUSIONS: Greater understanding about the predictors of ICH, mRS scores, and mortality could enable better selection of patients and treatments.

Circulation of mumps virus genotypes in Spain from 1996 to 2007.

Although the WHO recommends the use of genotyping as a tool for epidemiological surveillance for mumps, limited data on mumps virus (MV) genotype circulation that may be used to trace the patterns of virus spread are available. We describe the first complete series of data from Spain. The small hydrophobic region was sequenced from 237 MV-positive samples from several regions of Spain collected between 1996 and 2007. Six different genotypes were identified: A, C, D (D1), G (G1, G2), H (H1, H2), and J. Genotype H1 was predominant during the epidemic that occurred from 1999 to 2003 but was replaced by genotype G1 as the dominant genotype in the epidemic that occurred from 2005 to 2007. The same genotype G1 strain caused concomitant outbreaks in different parts of the world (the United States, Canada, and the United Kingdom). The remaining genotypes (genotypes A, C, D, and J) appeared in sporadic cases or small limited outbreaks. This pattern of circulation seems to reflect continuous viral circulation at the national level, despite the high rates of vaccine coverage.

Treatment of posterior circulation strokes by mechanical thrombectomy with a stent-retriever: a retrospective observational study at a single center. / Tratamiento del ictus de circulación posterior mediante trombectomía mecánica con stent-retriever: un estudio observacional, monocéntrico y retrospectivo.

OBJECTIVES: To determine the rate of recanalization, functional outcome at three months, and independent prognostic factors in patients with posterior circulation strokes treated with stent-retrievers and to compare these results with those of patients in an earlier series treated with "classical methods". MATERIAL AND METHODS: This was a retrospective study of consecutive patients with posterior circulation strokes treated with stent-retrievers at our center between December 1, 2011 and May 1, 2018. The main outcome variables were the rate of recanalization according to the Thrombosis in Cerebral Infarction (TICI) scale and functional independence score 90 days after treatment according to the modified Rankin Scale (mRS). We analyzed demographics, cerebrovascular risk factors, clinical findings, and probable origin. Descriptive statistics and a binary logistic regression model were used to analyze the data. RESULTS: We included 75 patients: 27 treated with "classical methods" and 48 treated with stent-retrievers (10 women; mean age, 63.9 years; median National Institute of Health Stroke Score, 15.8 (IQR 9-25); median Glasgow Coma Scale (GCS), 9.1 (IQR 6-14,5). TICI 2b-3 recanalization was achieved in 46 (95.8%) patients treated with stent-retrievers and in 15 (55.6%) patients treated with "classical methods" (p<0.0001). No significant differences were observed in the rate of patients achieving mRS 0-2 at 90 days (19 (39.6%) of those treated with stent-retrievers vs. 6 (22.2%) of those treated with "classical methods"). Mortality was lower among patients treated with stent-retrievers (14 (29.2% vs. 15 (55.6%) in those treated with "classical methods", p=0.024). GCS score was independently associated with mRS at 90 days (OR:0.67; 95%CI:0.5-0.91; p=0.01). CONCLUSIONS: In patients with posterior circulation infarcts, treatment with stent-retrievers achieved high rates of recanalization and functional independence at 90 days. The rate of complications was similar to those reported in other studies. GCS is an independent predictor of functional independence at 90 days.

Tumour suppressors and the regulation of GTP-binding protein activity.

GTP-binding proteins regulate a wide variety of intracellular signalling pathways in eukaryotic cells. The Ras GTP-binding proteins have received a great deal of attention since they were found to be modified by amino acid substitutions in a large number of cancers. It is now clear that Ras plays an essential role in regulating normal cell growth and differentiation, although how this is achieved biochemically is not known. The cellular concentration of Ras bound to GTP appears to be the limiting factor for signalling, and, not surprisingly, it is tightly controlled by both positive and negative regulators. There is now convincing evidence that the loss of one of these negative regulators of Ras, neurofibromin, can contribute to the development of malignancy; thus, neurofibromin behaves as a tumour suppressor gene product.

Cloning of a Grb2 isoform with apoptotic properties.

Growth factor receptor-bound protein 2 (Grb2) links tyrosine-phosphorylated proteins to a guanine nucleotide releasing factor of the son of sevenless (Sos) class by attaching to the former by its Src homology 2 (SH2) moiety and to the latter by its SH3 domains. An isoform of grb2 complementary DNA (cDNA) was cloned that has a deletion in the SH2 domain. The protein encoded by this cDNA, Grb3-3, did not bind to phosphorylated epidermal growth factor receptor (EGFR) but retained functional SH3 domains and inhibited EGF-induced transactivation of a Ras-responsive element. The messenger RNA encoding Grb3-3 was expressed in high amounts in the thymus of rats at an age when massive negative selection of thymocytes occurs. Microinjection of Grb3-3 into Swiss 3T3 fibroblasts induced apoptosis. These findings indicate that Grb3-3, by acting as a dominant negative protein over Grb2 and by suppressing proliferative signals, may trigger active programmed cell death.

Eliminating congenital rubella syndrome in Spain: does massive immigration have any influence?

In this short report we highlight the importance of implementing good immunization programs adapted to the epidemiological situation of rubella and congenital rubella syndrome (CRS), discuss the influence of massive immigration and stress the need to improve surveillance and control by implementing comprehensive national surveillance and promoting awareness among primary healthcare workers and midwives to find out any signs and symptoms compatible with rubella in pregnant women who have recently arrived from countries with high susceptibility to rubella infection.

Intracranial developmental venous anomaly: is it asymptomatic? / Anomalía venosa del desarrollo intracraneal. ¿Asintomática?

Intracranial developmental venous anomalies are the most common vascular malformation. In the immense majority of cases, these anomalies are asymptomatic and discovered incidentally, and they are considered benign. Very exceptionally, however, they can cause neurological symptoms. In this article, we present three cases of patients with developmental venous anomalies that presented with different symptoms owing to complications derived from altered venous drainage. These anomalies were located in the left insula, right temporal lobe, and cerebellum. The exceptionality of the cases presented as well as of the images associated, which show the mechanism through which the symptoms developed, lies in the low incidence of symptomatic developmental venous anomalies reported in the literature.

Incidence, prognosis, and prediction of haemorrhagic transformation after revascularisation for stroke. / Incidencia, pronóstico y predicción de la transformación hemorrágica tras el tratamiento revascularizador del ictus.

INTRODUCTION: Haemorrhagic transformation is a major complication of acute ischaemic stroke (AIS). We sought to determine the predictors and clinical impact of intracranial haemorrhage (ICH) after revascularisation therapy. METHODS: We conducted a retrospective, single-centre study including 235 patients with AIS who underwent intravenous recombinant tissue plasminogen activator (IV-rtPA) therapy and/or endovascular treatment. A binary logistic regression model was used to determine the variables associated with ICH, parenchymal haematomas (PH), modified Rankin Scale (mRS) scores, and mortality. RESULTS: ICH was detected in 57 (30 with PH) of 183 patients included. Mechanical thrombectomy, either alone (OR 3.3 [1.42-7.63], P=.005) or in combination with IV-rtPA (OR 3.39 [1,52-7.56], P=.003), was associated with higher risk of ICH, while higher Alberta Stroke Program Early CT scores (OR 0.71 [0.55-0.91], P=.007) were associated with lower risk. Patients with older age (OR 1.07 [1.02-1.13], P=.006) and occlusion of the terminal branch of the internal carotid artery (OR 4.03 [1.35-11.99], P = .012) had a higher risk of PH, while the use of IV-rtPA alone (OR 0.24 [0.08-0.68], P=.008) was associated with lower risk of PH. Only PH was associated with disability as measured by the mRS (OR 3.2 [1.17-8.76], P=.02) and higher mortality (OR 5.06 [1.65-15.5], P=.005). CONCLUSIONS: Greater understanding about the predictors of ICH, mRS scores, and mortality could enable better selection of patients and treatments.

Electronic Collection of Multilingual Patient-Reported Outcomes across Europe.

BACKGROUND: Patient-reported outcomes (PROs) are information provided directly by patients that helps in improving patient diagnosis and treatment. Validated translations of PROs can be used to treat international patients. Electronic systems and especially mobile devices provide a great opportunity for their collection; however, these systems are normally study-oriented and therefore single language, not scalable, and not interoperable. OBJECTIVES: This article reports the development of a multicenter, multilingual, and interoperable electronic PRO (ePRO) system and evaluates its user satisfaction in an international clinical study. METHODS: The ePRO named "MoPat2" was developed using Java 8 and jQuery Mobile 1.4.5. The system was evaluated in the context of the European dermatology project "European Network on Assessment of Severity and Burden of Pruritus"(PruNet), which aimed to unify the assessment of itch in routine dermatological care in Europe. Twenty-six clinicians and 468 patients from 8 European clinical centers were asked to complete a user satisfaction questionnaire regarding the use of MoPat2 with a tablet personal computer. The results were then analyzed and correlated with the age, gender, and language of the respondents. RESULTS: MoPat2 was enhanced with multilingual capabilities and is now able to conduct surveys in several languages, as well as store and display the results in the local language. The interviewed clinicians rated the system with an average score of 2.0 ("good") in a 1 to 5 Likert scale. Note that 93.9% of the patients (439 of 468) reported having got on well using the system and 88.9% (416 of 456) would be willing to further use it. The age of the patients not willing to further use MoPat2 was, in average, considerably higher than the age of patients willing to use the system. CONCLUSIONS: This study represents the first use of an ePRO system for the collection of multilingual PROs in an international, multicenter setting. MoPat2 has been evaluated by both clinicians and patients in the context of a European dermatological study, resulting in a high user satisfaction. The system will be further developed to include new features such as patient follow-ups outside of the clinical setting.

Antibodies to synthetic peptide from the residue 33 to 42 domain of c-Ha-ras p21 block reconstitution of the protein with different effectors.

Residues 32 to 40, which are conserved among ras proteins from different species, are likely to participate in interactions with the p21 effector system. With the goal of understanding the structural basis of the regulatory functions of c-Ha-ras p21, we produced rabbit antisera against a synthetic peptide corresponding to amino acids 33 to 42 of the protein. The affinity-purified antibodies interacted specifically with p21 and with the antigenic peptide. The epitope recognized by the antibodies appeared to be centered on threonine 35. The antibodies inhibited both in vitro p21-induced production of cyclic AMP in detergent extracts of RAS-defective yeast membranes and GAP-stimulated GTPase activity. However, monoclonal anti-ras antibodies Y13-259 and Y13-238 were not capable of specifically inhibiting interactions of p21 with these two putative effector proteins. The apparent inhibitory effect of Y13-259 on stimulation of p21 by GAP was due to a greatly reduced rate of exchange of nucleotides in the binding pocket of the protein. These findings provide additional support for the essential role of the residue 32 to 40 domain as the true effector site and further evidence of the involvement of GAP as a cellular effector of ras proteins.

[Cardiogenic shock due to acute myocarditis complicating leptospirosis]. / Choc cardiogénique par myocardite aiguë révélant une leptospirose.

A 48 year old man was admitted to the intensive care unit with septicaemic shock associated with febrile jaundice and anuric renal failure. Within hours, he developed cardiogenic shock with multi-organ failure due to an acute myocarditis refractory to catecholamines and requiring intra-aortic balloon pumping. The diagnosis was an ictero-haemorrhagic leptospirosis, the outcome of which was finally favourable. Myocarditis is an underestimated complication of leptospirosis because it is often symptomless. The main signs are arrhythmias, conduction defects and ST-T wave abnormalities which have little clinical expression. The disease may progress and is sometimes fatal. Leptospirosis myocarditis should therefore be carefully considered because of its potential severity and its reversibility with appropriate antibiotic therapy and also the necessity of initial management in a specific infrastructure.

[Esthesioneuroblastoma. Description of a case and review of the literature]. / Estesioneuroblastoma. Presentación de un caso clínico y revisión de la bibliografía.

The esthesioneuroblastoma is a malignant and rare type of the nasal cavity. Affected patients usually present with a progressive nasal obstruction, rhinorrea and epistaxis. Metastasis occurs in about 30% of patiens, the most common sites for metastasis are the cervical lymph nodes, less frequent in anothers organs. The optimum management is probably surgery combined with radiotherapy, the chemotherapy is usually reserved for local advanced tumor