Measurement Assessment of Minimal Disease Activity In Psoriasis in Spain: A National Cross-Sectional Study. / Valoración de la medida de Actividad Mínima de Enfermedad en Psoriasis en España: estudio transversal nacional.

INTRODUCTION: In 2017, the Spanish Academy of Dermatology and Venereology Psoriasis Working Group (PWG) designed the Minimal Disease Activity (MDA) criteria to determine the level of disease activity. We hereby present the results of an observational, cross-sectional, multicenter study of the nationwide application of these criteria. MATERIAL AND METHODS: We conducted a non-randomized sampling, stratified to achieve autonomic and provincial representation of consecutive patients with psoriasis (Ps) vulgaris without active arthritis. A total of 830 patients were included: 493 men (59.5%), with a mean age of 51.4 years (SD, 14.2), from all autonomous regions of Spain (except for Ceuta and Melilla) and 44 (88%) out of the 50 provinces. A questionnaire was obtained with demographic data, DLQI, subjective assessment-on a scale from 0 to 10-of itching, erythema, desquamation, visibility, and the patients' PASI and BSA. RESULTS: More than 50% failed to meet the MDA criteria (491; 59.2%), with significant differences being reported by region, sex, and age. Additionally, significant differences were reported based on the therapy used (P<.001). The use of biological therapies was associated with higher MDA compliance compared to other therapies (59.4% vs 23.3%). No differences were reported among various biological therapies. CONCLUSIONS: The overall rate of MDA compliance is low, with differences being based on geographic location, sex, age, and drug used, yet none of these factors separately justify them.

Valoración de la medida de Actividad Mínima de Enfermedad en Psoriasis en España: estudio transversal nacional.

INTRODUCTION: in 2017, the Spanish Academy of Dermatology and Venereology Psoriasis Working Group (PWG) designed the Minimal Disease Activity (MDA) criteria to determine the level of disease activity. We hereby present the results of an observational, cross-sectional, multicenter study of the nationwide application of these criteria. MATERIAL AND METHODS: we conducted a non-randomized sampling, stratified to achieve autonomic and provincial representation of consecutive patients with psoriasis (Ps) vulgaris without active arthritis. A total of 830 patients were included: 493 men (59.5%), with a mean age of 51.4 years (SD, 14.2), from all autonomous regions of Spain (except for Ceuta and Melilla) and 44 (88%) out of the 50 provinces. A questionnaire was obtained with demographic data, DLQI, subjective assessment-on a scale from 0 to 10-of itching, erythema, desquamation, visibility, and the patients' PASI and BSA. RESULTS: more than 50% failed to meet the MDA criteria (491; 59.2%), with significant differences being reported by region, sex, and age. Additionally, significant differences were reported based on the therapy used (p < 0.001). The use of biological therapies was associated with higher MDA compliance compared to other therapies (59.4% vs 23.3%). No differences were reported among various biological therapies. CONCLUSIONS: the overall rate of MDA compliance is low, with differences being based on geographic location, sex, age, and drug used, yet none of these factors separately justify them.

Independent validation of the adjusted GAPSS: Role of thrombotic risk assessment in the real-life setting.

Objective The objective of this report is to independently validate the adjusted Global Antiphospholipid Syndrome Score (aGAPSS) to predict thrombosis in a cohort of patients with APS and/or autoimmune disease. Methods This retrospective cohort study included 319 consecutive patients with APS and/or autoimmune disease. Data on clinical manifestations, conventional cardiovascular risk factors and aPL profile were collected. The aGAPSS was calculated for each patient by adding together the points corresponding to the risk factors. Results Among the 319 patients included (mean age: 48.0; SD 15.47), conducted over a mean period of 52 months (range: 19-394), 219 fulfilled the current APS classification criteria (PAPS diagnosed in 130 patients and APS associated autoimmune disease (aAPS) in 89 patients), and 100 patients with autoimmune disease without APS (AD). A total of 201 patients (63.0%) had a history of one or several thrombotic manifestations, 189 (86.3%) of them APS patients: 118 PAPS (mean age: 50.14; SD 15.47) and 71 aAPS (mean age: 48.13; SD 15.81). Higher aGAPSS baseline values were seen in patients with thrombosis 6.58 (SD 3.36) when compared with those without 4.90 (SD 4.33) ( p = 0.001). Conclusions This study has shown that even when anti-phosphatidylserine/prothrombin antibodies (aPS/PT) are not computed in an adjusted model of GAPSS (aGAPSS), this score represents an improvement in assessment of the risk prediction of thrombosis in APS patients and/or autoimmune disease. However, cut-off values may differ from other kinds of cohorts, which suggests that baseline characteristics in divergent groups of patients can account for differences in cut-off values of GAPSS.

Sentinel lymph node biopsy plus wide local excision vs. wide location excision alone for primary cutaneous melanoma: a systematic review and meta-analysis.

BACKGROUND: Sentinel lymph node biopsy and wide local excision of the primary melanoma (SLNB) is now a standard staging procedure for patients with melanomas 1 mm or more in thickness, but its therapeutic benefit is not clear. OBJECTIVE: To determine whether there is an association between performance of SLNB and patient prognosis. METHODS: Studies assessing the association between performance of SLNB and patient prognosis were pooled from MEDLINE, EMBASE, PubMed, Cochrane Database of Systematic Reviews and Google Scholar. From each study, first author's last name, publication year, origin country, type of study design, characteristics of participants and the Hazard risk (HR) for melanoma specific survival (MSS) with the corresponding 95% confidence interval (95% CI) were collected. Methodological assessment of the studies was evaluated using the Newcastle-Ottawa scale (NOS) and the 'Risk of bias' tool detailed in the Cochrane Handbook for Systematic Reviews of Interventions. Meta-analyses for the global HR were performed. In addition, in order to explore the sources of heterogeneity among the studies, sensitivity analyses are also provided. RESULTS: A total of six studies with 8764 patients who had undergone SLNB and 11054 patients who had undergone wide location excision alone (WLEA) were identified for the analysis. The indicators suggest that the heterogeneity is low: τ2  = 0; H = 1 [1; 1.74]; I2  = 0% [0%; 66.5%]. Evidence for publication bias was not found (Egger's test P = 0.4654). The pooled MSS HR from fixed effects analysis was determined to be 0.88 (95% CI = 0.80-0.96). CONCLUSIONS: Although no significant survival difference was observed in four of the six series, the pooling summary data from all the studies that deal with this issue suggested that SLNB is associated with a significantly better outcome compared with WLEA for localized melanoma.

Is external cephalic version at term contraindicated in previous caesarean section? A prospective comparative cohort study.

OBJECTIVE: To determine if external cephalic version (ECV) can be performed with safety and efficacy in women with previous caesarean section. DESIGN: Prospective comparative cohort study. SETTING: Cruces University Hospital (Spain). POPULATION: Single pregnancy with breech presentation at term. METHODS: We compared 70 ECV performed in women with previous caesarean section with 387 ECV performed in multiparous women (March 2002 to June 2012). MAIN OUTCOME MEASURES: Success rate, complications of the ECV and caesarean section rate. RESULTS: The success rate of ECV in women after previous caesarean section was 67.1% versus 66.1% in multiparous women (P = 0.87). The logistic regression analysis confirmed this result (odds ratio 0.93, 95% CI 0.52-1.68; P = 0.82) adjusted by the variables associated with success of ECV. There were no complications in the previous caesarean section cohort. The vaginal delivery rate in the previous caesarean section cohort was 52.8% versus 74.9% in the multiparous cohort (P < 0.01). There were no cases of uterine rupture. CONCLUSION: Based on our data, we conclude that complications are uncommon with ECV in women with previous caesarean section, with a success rate comparable to that of multiparous women. Uterine scar should not be considered a contraindication and ECV should be offered to women with previous caesarean section with breech presentation at term.

Psoriasis and hypertension: a case-control study.

BACKGROUND: Several studies stated that patient with psoriasis carried an increased risk of psoriasis but some studies did not demonstrate this association. OBJECTIVES: The aim of this study was to evaluate the prevalence of hypertension in psoriasis based on a sample of Spanish population. METHODS: This was a hospital-based case-control study involving 661 psoriatic patients (cases) and 661 control matched by gender and age. Meta-analysis of the previous studies was made. RESULTS: The prevalence of hypertension was significantly higher in psoriasis patients than controls (30.3%, 21.3%, respectively, P < 0.001). In a multivariate analysis, hypertension was associated with psoriasis after controlling for age, gender, diabetes, obesity and smoking (OR = 1.44, 95% confidence interval: 1.07-1.94). CONCLUSION: The results of this study support the association between psoriasis and hypertension.

Acute renal failure caused by imiquimod 5% cream in a renal transplant patient: review of the literature on side effects of imiquimod.

Imiquimod is an immunomodulator of the imidazoquinoline group which possesses antiviral and antitumour activities. Although its mechanism of action has not been entirely elucidated yet, imiquimod 5% cream has been shown to be an efficient, long-lasting and safe therapy for multiple actinic keratoses in non-immunosuppressed patients and in transplant recipients. We report the case of a 44-year-old patient with a third renal transplant who developed an acute tubular necrosis confirmed by renal biopsy after the use of imiquimod 5% cream. The result of a literature search revealed a wide variety of side effects attributable to the use of imiquimod.

Lectin-like transcript 1 (LLT1) expression is associated with nodal metastasis in patients with head and neck cutaneous squamous cell carcinoma.

The interaction of lectin-like transcript 1 (LLT1) with CD161 inhibits Natural Killer cell activation. Overexpression of LLT1 contributes to the immunosuppressive properties of tumor cells. However, there are little data about LLT1 expression in human solid tumors. The objective of this paper is to investigate the relationship between LLT1 expression with the clinicopathologic features and its impact on the prognosis of head and neck cutaneous squamous cell carcinoma (cSCC). LLT1 expression was analyzed on paraffin-embedded tissue samples obtained from 100 patients with cSCC by immunohistochemistry. The estimator of Fine and Gray was used to estimate the cumulative incidence curves for relapse. Proportional Hazard models and Hazard ratios (HRs) were used for studying the risk of tumor relapse and mortality. LLT1 strong expression was a significant risk factor for nodal metastasis with crude and adjusted ratios (HRs) of 3.40 (95% CI 1.39-9.28) and 3.25 (95% CI 1.15-9.16); and for cSCC specific death of 6.17 (95% CI 1.79-21.2) and 6.10 (95% CI 1.45-25.7). Strong LLT1 expression is an independent predictor of nodal metastasis and poor disease-specific survival and it might be helpful for risk stratification of patients with cSCC.

Genetic heterogeneity of BCR/ABL+ adult B-cell precursor acute lymphoblastic leukemia: impact on the clinical, biological and immunophenotypical disease characteristics.

Philadelphia-positive (Ph(+)) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a genetically heterogeneous disease with a very poor prognosis. In this study, we analyzed the frequency of supernumerary Ph, trisomy 8, monosomy 7, and del(9p21) by FISH and its relationship with the characteristics of the disease, in 46 BCR/ABL(+) adult BCP-ALL patients. The frequency of supernumerary Ph, trisomy 8, monosomy 7 and del(9p21) was 30%, 20%, 15%, and 24%, respectively. Although all patients displayed a BII/common phenotype, supernumerary Ph and trisomy 8 were associated with higher expression of CD19 and CD22 and of CD19, CD34, CD45, and HLA-DR, respectively; in turn, cases with monosomy 7 showed lower CD19, CD22, CD34, and cCD79a and del(9p21)(+) blasts were CD13(-) and CD33(-). Overall, similar clinical and hematological features were observed at presentation, independently of the underlying genetic abnormalities. However, relapse-free survival (RFS) was significantly shorter in cases with supernumerary Ph, trisomy 8, and del(9p21), the latter being the most powerful independent prognostic factor for RFS.

Purification and properties of three proteases from the larvae of the brine shrimp Artemia salina.

Three proteases, termed A, B and C, have been characterized and partially purified from Artemia salina larvae. Enzyme A is active on benzyloxycarbonyl L-leucin p-nitrophenyl ester (Km = 53 micron, determined at pH 8 and 37 degrees C) but not on alpha-N-benzoyl-DL-arginine p-nitroanilide and is strongly inhibited by micron concentrations of phenylmethylsulfonylfluoride. Enzymes B and C are active on alpha-N-benzoyl-L-arginine p-nitroanilide (Km = 20 and 11 micron, respectively) but not on benzyloxycarbonyl-L-leucine p-nitrophenyl ester and B, but not C, is inhibited by mM concentrations of phenylmethylsulfonyfluoride. Enzymes A, B and C are optimally active at alkaline pH values, do not require either metal ions or -SH groups for their catalytic activity and have molecular weights of 38 000, 33 000 and 34 000, respectively. After heating for 5 min at pH 7.5 and in the presence of 0.7 M KCl half inactivation of proteases A, B and C was attained at 60, 52 and 45 degrees C, respectively.

[Incidence of febrile episodes in patients with multiple myeloma undergoing autologous peripheral blood stem cell transplantation]. / Incidencia de episodios febriles en pacientes con mieloma múltiple sometidos a trasplante autólogo de progenitores hematopoyéticos de sangre periférica (TASPE).

BACKGROUND: Autologous peripheral blood stem cell transplantation (PBSCT) is a procedure frequently used as therapy for hematological malignancies, in which infectious complications are a major cause of morbimortality. The duration and intensity of neutropenia, indwelling central venous catheters, and mucosa chemotherapy-induced damage, contribute to increase infection rates. We have retrospectively review the incidence of febrile episodes and microbiological documented infections (MDI) in patients with multiple myeloma (MM) undergoing PBSCT. PATIENTS AND METHODS: We have retrospectively analyzed 56 PBSCT in patients diagnosed of MM between 1995 and 2002 in our hospital. RESULTS: 34 patients showed fever: 19 fever of unknown origin; 5 clinically documented infections and 10 patients MDI. We isolated 5 pathogens gram negative and 4 gram positive. We observed 2 infections associated to indwelling central venous catheters and 1 MDI due to simplex Herpes Virus. Two patients died due to infectious complications. CONCLUSIONS: The incidence of febrile episodes in our patients is similar to those previously reported as well, duration of neutropenia associated to PBSCT. We have observed a slightly higher incidence of gram negative pathogens.

Management of breech presentation at term: a retrospective cohort study of 10 years of experience.

OBJECTIVE: To evaluate the impact of management of childbirth (external cephalic version (ECV) plus planned vaginal delivery (PVD)) of breech presentation at term (⩾37 weeks of gestation). STUDY DESIGN: This retrospective cohort study was based on data collected of singleton breech presentations at term in the Obstetrics and Gynaecology Service, Cruces University Hospital (Biscay, Spain), from January 2003 to December 2012. RESULT: We attended 2377 singleton breech pregnancies at term. We attended 1684 singleton breech term deliveries, attempting vaginal delivery after selection in 52.9% of cases and were successful in 57.5% of attempts. A total of 1360 ECV were attempted, with a success rate of 50.3% of those attempted. The use of ECV has decreased the rate of breech presentation at delivery by 39.0%, the rate of breech presentation as a caesarean section (CS) indication by 47.1% (CS due to breech presentation/total of CS) and the rate of CS for breech presentation out of the total of deliveries by 39.1% (CS due to breech presentation/total of deliveries). Early postnatal parameters (5-min Apgar score, umbilical cord arterial pH and acid-base analysis) were significantly lower following PVD compared with planned CS for breech presentation. However, we did not find any differences in the rates of admissions to the neonatal unit or neonatal mortality. CONCLUSION: Management of breech presentation with a protocol that includes ECV, careful selection criteria and active management of vaginal delivery achieve a great decrease in the rate of CS for breech presentation.

Nocturnal increases in the triiodothyronine/thyroxine ratio in the rat thymus and pineal gland follow increases of type II 5'-deiodinase activity.

The type II 5'-deiodinase (5'D-II) is regulated by the light-dark cycle in some tissues in which the enzyme is present. This prompted us to investigate putative influences of light-dark cycle on thyroid hormone concentrations in these tissues. The results revealed the following facts: (a) Deiodinase activity in the rat thymus exhibits a nyctohemeral profile with peak values late at night and basal values during the day. The thyroid hormone concentrations in the thymus also show a 24 h rhythm with an increase in the triiodothyronine/thyroxine (TT3/TT4) ratio at night. (b) The content of thyroid hormones in the pineal gland exhibits, like in the thymus, nyctohemeral variations with increase values in the TT3/TT4 ratio during the dark period coinciding with the maximal enzyme activity. (c) Other tissue, like the anterior pituitary, in which 5'D-II, activity does not exhibit a diurnal variation, the concentration of thyroid hormones does not show modifications. In conclusion, the nocturnal increase of 5'D-II activity produces an increase of T3 concentration and a decrease of T4 concentration in both thymus and pineal gland. Therefore, these diurnal changes in 5'D-II activity is a mean by which the cell can regulate the intracellular availability of the most active thyroid hormone T3.

Beta- and alpha-adrenergic mechanisms are involved in regulation of rat pineal type II thyroxine 5'-deiodinase activity during development.

Adrenergic regulation of type II T4 5'-deiodinase (5'-D) activity has been studied in the rat pineal gland during development. Nocturnal increases in 5'-D activity gradually rose from the second week of age until the sixth week. Isoproterenol, a beta-adrenergic agonist, stimulated 5'-D activity during the daytime; however, the pattern of stimulation during development was slightly different from nocturnal activation of the enzyme, since pineal 5'-D activity could be clearly activated by isoproterenol from the first week of age. Isoproterenol activation of the enzyme always reached more than 70% of nocturnal values at all ages studied. Phenylephrine, an alpha-adrenergic agonist, did not increase the enzyme activity. Another selective alpha-adrenergic agonist, methoxamine, as well as clonidine, an alpha 2-adrenergic agonist, were ineffective in stimulating the enzyme, while norepinephrine or terbutaline, a beta-adrenergic agonist, clearly activated it. Additional results showing a role for alpha-adrenergic receptors on pineal 5-D activity were obtained when alpha- and beta-adrenergic receptor blockers were used. Thus, propranolol, a beta-adrenergic blocker, clearly prevented pineal 5'-D activation in both 2- and 6-week-old rats when the gland was stimulated by either norepinephrine or darkness at night. However, prazosin, a selective alpha 1-adrenergic receptor blocker, also prevented the norepinephrine-induced or darkness-induced activation of the enzyme in 2-week-old rats, although it was ineffective when used in 6-week-old rats. Moreover, at night and after 3 h of exposure to darkness, phenylephrine was able to activate the enzyme. Results strongly suggest a role for alpha-adrenergic receptors, in addition to beta-adrenergic receptors, in regulating rat pineal 5'-D activity during development.

Involvement of alpha- and beta-adrenergic receptors in the regulation of rat pineal N-acetyltransferase activity during development.

The regulation by alpha- and beta-adrenergic receptor agonists of rat pineal N-acetyltransferase (NAT) activity during development was studied. We found that isoproterenol, a beta-adrenergic agonist, exhibited a weak stimulatory effect on pineal NAT activity during the first 3 weeks of age. Indeed, the drug did not mimic the effect of darkness on pineal NAT activity until the fourth week of age. The results might be explained by the existence of other mechanisms, in addition to those that involve beta-adrenergic receptors, which regulate pineal NAT activity during early postnatal development. In line with this, we determined that phenylephrine, an alpha 1-adrenergic agonist, stimulated NAT activity during both the day and at night in 2-week-old rats, while exhibiting no effect in adult rats. Methoxamine, an alpha 1-adrenergic agonist more selective than phenylephrine, also activated NAT activity in young, but not in adult, rats. Moreover, prazosin, a selective alpha 1-adrenergic receptor blocker, prevented pineal NAT activation by norepinephrine or darkness at night in 2-week-old rats, but not in adult animals. The results suggest that alpha 1-adrenergic receptors may be more important than beta-adrenergic receptors in regulating rat pineal NAT activity during development.

Impaired calcium sequestration activity in liver microsomes from fasted rats.

Calcium uptake activity was assayed in liver microsomal vesicles from fed and fasted rats. This activity required ATP and was stimulated by the calcium trapping agent oxalate. The most striking feature was the low rate of calcium accumulation in liver microsomes from fasted rats. Maximal rate was inhibited up to 66 and 82% after 1 and 3 days starvation, respectively. This defective microsomal calcium handling suggests its possible involvement in the massive glycogen breakdown during starvation.

Expression of type II thyroxine 5'-deiodinase from rat harderian gland in Xenopus laevis oocytes.

The presence of isoenzymes mediating the conversion of thyroxine to 3,5,3'-triiodothyronine has been studied according to characteristic kinetics and physiological regulation. In this paper, we report the expression of type II 5'-deiodinase (5'D) activity in oocytes of Xenopus laevis. Oocytes injected with total RNA extracted from rat Harderian gland, and then incubated up to five days demonstrated a progressive increase in 5'D activity, reaching a maximal value at 24 h; then, 5'D activity remained almost stable for an additional period of four days. Characteristics of the enzyme activity expressed by oocytes included its inhibition by iopanoic acid, but not by propylthiouracil, and its increase during beta-adrenergic agonist treatment and hypothyroidism. The expressed activity manifests characteristics typical of the type II isoenzyme. Deiodinating activity in oocytes also exhibited diurnal variations. In this study, 5'D activity expressed in oocytes exhibited low values when animals were killed during the day, and high values when animals were killed at night. Maximal values were reached 3-4 h before the nocturnal peak of 5'D activity in Harderian gland crude homogenates. Results suggest that the in vivo activation of 5'D by isoproterenol, hypothyroidism, or dark exposure may be caused by an increase in the synthesis and/or maturation of the RNA expressing the enzyme.

The immunohistochemical diagnostic panel for epithelial mesothelioma: a reevaluation after heat-induced epitope retrieval.

The immunohistochemical diagnosis between epithelial mesothelioma and adenocarcinoma is currently based on the use of a panel of antibodies to adenocarcinoma-associated antigens and a few antibodies to mesothelial-associated antigens. Since the introduction of epitope retrieval methods, the sensitivity of many antibodies has been enhanced. Thus, a reevaluation of the mesothelioma/adenocarcinoma diagnostic panel becomes necessary. We studied 268 paraffin-embedded formalin-fixed tumor samples that included 57 epithelial mesotheliomas and 211 adenocarcinomas of various origins, comparing an extensive antibody panel with and without heat-induced epitope retrieval (HIER). Marked increase in the sensitivity of several antibodies, with no loss of specificity, was found when HIER was used. After statistical analysis, the antibodies to the epithelial glycoproteins carcinoembryonic antigen, BerEp4, and Bg8 emerged as the best discriminators between adenocarcinoma and epithelial mesothelioma within the entire panel. The mesothelium-associated antibodies, HBME-1, calretinin, and thrombomodulin were less sensitive and less specific than the former, although they were found to be useful on certain cases. Antibodies to cytokeratins and vimentin, although of minor diagnostic value in this context, may be helpful to evaluate the quality of antigen preservation. This study confirms the value of immunohistochemistry to accurately distinguish mesothelioma from adenocarcinoma when an antibody panel approach is used. The addition of heat-induced epitope retrieval methods increases the effectiveness of the procedure and is recommended for most of the antibody panel members.