Mogamulizumab efficacy is underscored by its associated rash that mimics cutaneous T-cell lymphoma: a retrospective single-centre case series.

BACKGROUND: Mogamulizumab is a humanized antibody against chemokine receptor type 4. It was recently approved by the US Food and Drug Administration for relapsed or refractory mycosis fungoides (MF) and Sézary syndrome (SS). The most commonly reported adverse event in the phase III licensing trial was drug eruption (28%), now termed mogamulizumab-associated rash (MAR). Clinical recommendations about MAR and its treatment differ between the current package insert and postapproval insights reported from two single-centre studies that focused on its characterization, but less so on outcomes and clinicopathological differentiation from cutaneous T-cell lymphoma (CTCL). OBJECTIVES: To describe our experience in the diagnosis of MAR and treatment of patients with CTCL with mogamulizumab. METHODS: This is a single-centre retrospective case series study. RESULTS: We found a higher incidence of MAR in patients with CTCL (17 of 24, 68%) than previously reported. MAR development is associated with complete (11 of 17) or partial (four of 17) responses, with an overall response rate of 88%, compared with 29% (two of seven) in patients without MAR. Diagnosis of MAR may be obscured by its ability to mimic key CTCL features both clinically and histologically, but an absence of T-cell-receptor clonality and relatively decreased CD4 : CD8 ratio compared with baseline lesions strongly favour MAR over recurrent disease. CONCLUSIONS: MAR has the potential to create a significant management problem for patients on mogamulizumab. Misidentification of MAR as recurrent CTCL may detrimentally result in the premature discontinuation of mogamulizumab in patients whose disease is historically hard to treat. Thorough clinicopathological investigation of new lesions during treatment with mogamulizumab is required to inform ideal treatment decisions and achieve better outcomes.

Treatment of early-stage mycosis fungoides: results from the PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study.

BACKGROUND: The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is a prospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) in patients with newly diagnosed mycosis fungoides (MF). OBJECTIVES: To identify (i) differences in first-line approaches according to tumour-nodes-metastasis-blood (TNMB) staging; (ii) parameters related to a first-line systemic approach and (iii) response rates and QoL measures. METHODS: In total, 395 newly diagnosed patients with early-stage MF (stage IA-IIA) were recruited from 41 centres in 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review. RESULTS: The most common first-line therapy was skin-directed therapy (SDT) (322 cases, 81·5%), while a smaller percentage (44 cases, 11·1%) received systemic therapy. Expectant observation was used in 7·3%. In univariate analysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA, 20%; IA-IB vs. IIA, P < 0·001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0·001), higher modified Severity Weighted Assessment Tool (> 10, 15%; ≤ 10, 7%; P = 0·01) and folliculotropic MF (FMF) (24% vs. 12%, P = 0·001). Multivariate analysis demonstrated significant associations with the presence of plaques (T1b/T2b vs. T1a/T2a, odds ratio 3·07) and FMF (odds ratio 2·83). The overall response rate (ORR) to first-line SDT was 73%, while the ORR to first-line systemic treatments was lower (57%) (P = 0·027). Health-related QoL improved significantly both in patients with responsive disease and in those with stable disease. CONCLUSIONS: Disease characteristics such as presence of plaques and FMF influence physician treatment choices, and SDT was superior to systemic therapy even in patients with such disease characteristics. Consequently, future treatment guidelines for early-stage MF need to address these issues.

Tumor necrosis factor haplotype diversity in Mestizo and native populations of Mexico.

The so-called tumor necrosis factor (TNF) block includes the TNFA, lymphotoxin alpha and beta (LTA and LTB) genes with single-nucleotide polymorphisms (SNP) and microsatellites with an allele frequency that exhibits interpopulation variability. To date, no reports have included both SNPs and microsatellites at the TNF block to study Mestizo or Amerindian populations from Mexico. In this study, samples of five Mexican Mestizo populations (Durango, Guadalajara, Monterrey, Puebla, and Tierra Blanca) and four native-Mexican populations (North Lacandonians, South Lacandonians, Tepehuanos, and Yaquis) were genotyped for two SNPs (LTA+252A>G and TNFA-308G>A) and four microsatellites (TNFa, d, e, and f), to analyze the genetic substructure of the Mexican population. Allele and haplotype frequencies, linkage disequilibrium (LD), and interpopulation genetic relationships were calculated. There was significant LD along almost all of the TNF block but the lowest D' values were observed for the TNFf-TNFd pair. Mestizos showed higher allele and haplotype diversity than did natives. The genetic differentiation level was reduced among Mestizos; however, a slightly, but significant genetic substructure was observed between northern and southern Mexican Mestizos. Among the Amerindian populations, the genetic differentiation level was significantly elevated, particularly in both North and South Lacandonians. Furthermore, among Southern Lacandonians, inhabitants of Lacanja town were the most differentiated from all the Mexicans analyzed. The data presented here will serve as a reference for further population and epidemiological studies including these TNF polymorphisms in the Mexican population.

[Measurement of intra-abdominal pressure with intravesical system Unometer Abdo-Pressure]. / Medción de la presión intraabdominal con sistema intravesical Unometer Abdo-Pressure.

The measurement of intra-abdominal pressure (IAP) has been incorporated routinely in Critical Units in order to monitor and control those clinical situations that make us suspicious of intraabdominal hypertension (IAH). There are several methods to measure IAP [1-3]: direct measurement, a catheter inserted through suprapubic aspiration, although it is a discouraged procedure by being very invasive; and indirect measurement. In this method there are mainly three different techniques: Through femoral vein puncture: a catheter into the inferior vena cava is channeled. It is a technique being deprecated invasive, associated with venous thrombosis, retroperitoneal hematoma and infection. Through a gastric tube: impractical, requires managing large amounts of water associated with leakage through the pylorus risk. Through intravesical measurement: is the most commonly used method. The bladder catheter allows monitoring the PIA and diuresis and electrolyte control. This method has potential for infection associated with catheterization risk. Although this risk, it is considered the gold standard for the measurement of IAP. Have now been introduced to the market each measuring intravesical kits guaranteeing sterility circuit without disconnections. It is necessary to know the material and the correct procedure for measuring the PIA and how to interpret the results.

A quantitative speciation model for the adsorption of organic pollutants on activated carbon.

Granular activated carbon (GAC) is commonly used as adsorbent in water treatment plants given its high capacity for retaining organic pollutants in aqueous phase. The current knowledge on GAC behaviour is essentially empirical, and no quantitative description of the chemical relationships between GAC surface groups and pollutants has been proposed. In this paper, we describe a quantitative model for the adsorption of atrazine onto GAC surface. The model is based on results of potentiometric titrations and three types of adsorption experiments which have been carried out in order to determine the nature and distribution of the functional groups on the GAC surface, and evaluate the adsorption characteristics of GAC towards atrazine. Potentiometric titrations have indicated the existence of at least two different families of chemical groups on the GAC surface, including phenolic- and benzoic-type surface groups. Adsorption experiments with atrazine have been satisfactorily modelled with the geochemical code PhreeqC, assuming that atrazine is sorbed onto the GAC surface in equilibrium (log Ks = 5.1 ± 0.5). Independent thermodynamic calculations suggest a possible adsorption of atrazine on a benzoic derivative. The present work opens a new approach for improving the adsorption capabilities of GAC towards organic pollutants by modifying its chemical properties.

[Cell saver]. / Recuperador cellular.

The blood retrievers are instruments increasingly used in operating rooms. They are especially useful in operations where there is a high risk of bleeding and transfusion requirements are high. In paediatrics is of great importance in complex interventions in order to avoid allogeneic transfusion (blood collected from donors). The implementation of the recovery of blood in the surgical field is very simple and easy to use. This is a suction tube that collects the blood that is free, transferring it to a centrifuge where it is filtered and washed, stored in a blood collection bag for subsequent infusion. The blood is of high quality and contains a high hematocrit blood from the bank.

In Saccharomyces cerevisiae, withdrawal of the carbon source results in detachment of glycolytic enzymes from the cytoskeleton and in actin reorganization.

Metabolons are dynamic associations of enzymes catalyzing consecutive reactions within a given pathway. Association results in enzyme stabilization and increased metabolic efficiency. Metabolons may use cytoskeletal elements, membranes and membrane proteins as scaffolds. The effects of glucose withdrawal on a putative glycolytic metabolon/F-actin system were evaluated in three Saccharomyces cerevisiae strains: a WT and two different obligate fermentative (OxPhos-deficient) strains, which obtained most ATP from glycolysis. Carbon source withdrawal led to inhibition of fermentation, decrease in ATP concentration and dissociation of glycolytic enzymes from F-actin. Depending on the strain, inactivation/reactivation transitions of fermentation took place in seconds. In addition, when ATP was very low, green fluorescent protein-labeled F-actin reorganized from highly dynamic patches to large, non-motile actin bodies containing proteins and enzymes. Glucose addition restored fermentation and cytoskeleton dynamics, suggesting that in addition to ATP concentration, at least in one of the tested strains, metabolon assembly/disassembly is a factor in the control of the rate of fermentation.

Impact of prior pneumococcal vaccination on clinical outcomes in HIV-infected adult patients hospitalized with invasive pneumococcal disease.

BACKGROUND: Recent studies in hospitalized patients with community-acquired pneumonia have found a lower risk of bacteraemia and better clinical outcomes in patients who had previously received the 23-valent pneumococcal polysaccharide vaccine (PPV) in comparison with unvaccinated individuals. The aim of this study was to assess the influence of prior PPV on clinical outcomes in HIV-infected adult patients hospitalized with invasive pneumococcal disease (IPD). METHODS: This was an observational study of all consecutive HIV-infected adults hospitalized with IPD from January 1996 to October 2007 in three hospitals in Spain. Baseline characteristics and clinical outcome-related variables were compared according to prior PPV vaccination status. RESULTS: A total of 162 episodes of IPD were studied. In 23 of these (14.2%), patients had previously received PPV. In both vaccinated and unvaccinated patients, most of the causal serotypes were included in the 23-valent PPV (76.9% and 84.1%, respectively). Overall, 25 patients (15.4%) died during hospitalization, 21 patients (13%) required admission to an intensive care unit (ICU) and 34 patients (21%) reached the composite outcome of death and/or admission to the ICU. None of the 23 patients who had previously received PPV died or required ICU admission, in comparison with 25 (18%; P=0.026) and 21 (15.1%; P=0.046), respectively, of the unvaccinated patients. The length of hospital stay for vaccinated patients was significantly shorter (8.48 vs. 13.27 days; P=0.011). CONCLUSIONS: Although 23-valent PPV failed to prevent IPD in some HIV-infected patients, vaccination produced beneficial effects on clinical outcomes by decreasing illness severity and mortality related to IPD.

Association between adiposity levels and cognitive impairment in the Chilean older adult population.

Although both obesity and ageing are risk factors for cognitive impairment, there is no evidence in Chile on how obesity levels are associated with cognitive function. Therefore, the aim of the present study was to investigate the association between adiposity levels and cognitive impairment in older Chilean adults. This cross-sectional study includes 1384 participants, over 60 years of age, from the Chilean National Health Survey 2009-2010. Cognitive impairment was evaluated using the Mini-Mental State Examination. BMI and waist circumference (WC) were used as measures of adiposity. Compared with people with a normal BMI, the odds of cognitive impairment were higher in participants who were underweight (OR 4·44; 95 % CI 2·43, 6·45; P < 0·0001), overweight (OR 1·86; 95 % CI 1·06, 2·66; P = 0·031) and obese (OR 2·26; 95 % CI 1·31, 3·21; P = 0·003). The associations were robust after adjustment for confounding variables. Similar results were observed for WC. Low and high levels of adiposity are associated with an increased likelihood of cognitive impairment in older adults in Chile.

Bacterial pneumonia in HIV-infected patients: use of the pneumonia severity index and impact of current management on incidence, aetiology and outcome.

OBJECTIVES: Despite a recent decrease, bacterial pneumonia (BP) is still the most common admission diagnosis in HIV patients. We analyse BP incidence, characteristics and prevention measures. METHODS: Observational study of all patients hospitalized for BP in a tertiary hospital in Barcelona, Spain, from January 2000 to December 2005. Demographic and HIV-related data, BP risk factors, characteristics of BP and outcomes are analysed. RESULTS: One hundred and eighty-six BP episodes in 161 patients were included; patients were mainly male (73.7%) and intravenous drug users (73.7%). A decrease in BP incidence was seen during the study period, especially in vaccinated patients. The most commonly isolated microorganism was Streptococcus pneumoniae (31.7%), followed by Legionella pneumophila (5.9%). Legionella pneumophila was more likely in patients with undetectable viral load, higher CD4 cell counts or prior vaccination. Highly active antiretroviral therapy, cotrimoxazole prophylaxis and pneumococcal vaccination did not have a significant influence on bacteraemia rate, in-hospital complications or BP mortality. High Pneumonia Severity Index (PSI) predicted mortality accurately [relative risk 15.2, 95% confidence interval 3.2-71.7; P=0.001]. Mortality was 9.1%, but was significantly higher in patients with CD4 counts under 200 cells/microL (P=0.022). CONCLUSIONS: A decline in BP incidence was seen during the study period. Combining CD4 cell count and PSI score could become a good strategy in deciding which patients have to be hospitalized.

In Vitro Anthelmintic Activity of Methanolic Extract from Caesalpinia coriaria J. Willd Fruits against Haemonchus contortus Eggs and Infective Larvae.

The aim of this study was to evaluate the in vitro lethal effect of a methanolic extract (ME) from Caesalpinia coriaria fruits against Haemonchus contortus eggs and infective larvae. The anthelmintic activity was assessed using the egg hatching inhibition assay (EHI) and the mortality test. The ME was assessed using five concentrations as follows: 6.15, 3.12, 1.56, and 0.78 mg/mL to eggs and 150, 100, 75, and 50 mg/mL to larvae, respectively. Ivermectin (5 mg/mL) was used as positive control and 4% methanol and distilled water were used as negative controls. The data of ovicidal and larvicidal effect were analyzed with a completely randomized design through ANOVA analysis using the general linear model (GLM) and lethal concentrations (LC50 and LC90) were estimated through a Probit analysis using the SAS program. A clear ME increased concentration dependence effect was observed in the EHI and mortality tests. The highest activity of the methanolic extract was observed at the highest concentration (P < 0.05) to obtain a similar effect to the positive control (ivermectin), with LC50 = 78.38 and 0.00064 mg/mL and LC90 =235.63 and 0.024 mg/mL, respectively, for larvae and eggs. The results indicate that the C. coriaria fruit ME possesses in vitro ovicidal and larvicidal properties (gallotannins: methyl gallate) against H. contortus that needs to be investigated more in vivo for the control of gastroenteric nematodes in ruminants.

[Hypertension in hemodialysis: prevalence and associated factors in Catalonia. The PRESDIAL study]. / Prevalencia y factores asociados a hipertensión arterial en hemodiálisis en Cataluña. Estudio PRESIDIAL.

OBJECTIVE: To evaluate the prevalence of hypertension (HT) in prevalent hemodialysis (HD) patients in our region, and to analyze the associated clinical and biochemical variables. METHODS: Observational, cross-sectional and multicentric study including a representative sample of prevalent and stable (> 6 months) HD patients from all the HD centers (in and out of Hospitals) in Catalonia, Spain. Clinical and biochemical variables were recorded and predialysis blood pressure (BP) was determined (x3) in each dialysis session during 1 month, as well as the pre/post weight weekly. HT was defined as having at least one of these criteria: a mean (12 determinations) systolic BP > or = 140 mmHg or diastolic BP > or = 90 mmHg or antihypertensive treatment for at least 3 months. RESULTS: The sample comprised 387 patients from 32 of the 40 centers included, 231 of whom where men, with mean age of 63 +/- 14 years. The prevalence of HT in this sample was 67.4%, varying according to the etiology of End-Stage Renal Disease: diabetic 81%, vascular 81%, glomerulonephritis 61%, PKD 52%, unknown and others 64%. The prevalence of additional CV risk factors was 83%. One of each hypertensive 4 patients were treated, of whom 58% had systolic BP > or = 140 or dyastolic > or = 90, in contrast to 28% of untreated patients. The proportion of individuals according to the number of antihypertensive agents was 21% (no agents), 48% (1 agent), 20% (2 agents), 11% (3 agents). Blood pressure was higher among patients receiving higher number of antihypertensive agents. No differences according HT were found in age (64 +/- 13 in hypertensive patients versus 60 +/- 15 in normotensives), time on dialysis (4 +/- 4 vs 4 +/- 4 years), interdialysis weight gain (2.1 +/- 0.8 vs 2.1 +/- 0.8 kg), proportion of weight gain (3.3 +/- 1.4 vs 3.1 +/- 1.4%) or proportion of patients with > 5% weight gain with respect to dry weight (32.5 vs 27.3%). While 84% of hypertensive patients had an additional CV risk factor, this value was 67% in the patients without HT (p < 0.001). CONCLUSION: In HD patients HT has a high prevalence in our region and is poorly controlled. The causes of this poor control may be multiple, and weight gain parameters seem not to be a main factor in these stable patients. Due to the aggregation of risk factors in these patients, strategies in order to improve BP control in HD are mandatory.

Isolation of a conjugative F-like plasmid from a multidrug-resistant Escherichia coli strain CM6 using tandem shock wave-mediated transformation.

Genetic characterization of plasmids from bacterial strains provides insight about multidrug resistance. Ten wild type Escherichia coli (E. coli) strains isolated from cow fecal samples were characterized by their antibiotic resistance profile, plasmid patterns and three different identification methods. From one of the strains, a fertility factor-like plasmid was replicated using tandem shock wave-mediated transformation. Underwater shock waves with a positive pressure peak of up to approximately 40 MPa, followed by a pressure trough of approximately -19 MPa were generated using an experimental piezoelectric shock wave source. Three different shock wave energies and a fixed delay of 750 µs were used to study the relationship between energy and transformation efficiency (TE), as well as the influence of shock wave energy on the integrity of the plasmid. Our results showed that the mean shock wave-mediated TE and the integrity of the large plasmid (~70 kb) were reduced significantly at the energy levels tested. The sequencing analysis of the plasmid revealed a high identity to the pHK17a plasmid, including the replication system, which was similar to the plasmid incompatibility group FII. It also showed that it carried an extended spectrum beta-lactamase gene, ctx-m-14. Furthermore, diverse genes for the conjugative mechanism were identified. Our results may be helpful in improving methodologies for conjugative plasmid transfer and directly selecting the most interesting plasmids from environmental samples.

[Codification of psychosocial diagnoses]. / Codificación de los diagnósticos psicosociales.

Psychosocial pathology accounts for a significant proportion of pediatric practice. Its registry, however, is usually scanty or erratic. The purpose of this update was to collect and define psychosocial diagnoses within the ICM-9-CM coding system in order to aid pediatric practice and to offer interpretations of diagnoses, which would aid their coding.

[Usefulness of troponin T and troponin I in the diagnosis and prognostic stratification of patients with ischemic cardiopathy attending an emergency service]. / Utilidad de la troponina T y troponina I en el diagnóstico y estratificación pronóstica de los pacientes con cardiopatía isquémica que acuden a un Servicio de Urgencias.

BACKGROUND: Diagnostic of chest pain in the emergency services supposes a serious problem. This study wants objective if the new non enzymatic markers of myocardial necrosis (T troponin and I troponin) may be an aid for the diagnostic and prognostic stratification of patients with myocardial ischemia. PATIENTS AND METHODS: 82 successive patients who went to the emergency room for chest pain were studied. Electrocardiogram and blood samples were obtained at 0,4, and 12 house of admission. A clinic-evolutive study was performed at discharge, and they were classified in 3 categories: a) myocardial infarction, b) unstable angina (Braunwald classification) and no coronary pains. RESULTS: In the 27 patients with myocardial infarction the markers of troponin group were more sensitive than creatinine kinase to determine myocardial necrosis at 4 hours of admission. Of 41 patients with unstable angina, 34% were of Braunwald III-B class. Troponin group markers discriminate a group of high risk patients, 70% of the patients that need an emergency coronarography for bad clinical evolution were troponin group marker positive. CONCLUSIONS: The use in the emergency room of troponin necrosis markers (T and I troponin) allows to optimize the sanitary resources, detecting quickly the patients with acute myocardial infarction and discriminate a group of high risk of patients with angina.

Impact of the emergence of non-vaccine pneumococcal serotypes on the clinical presentation and outcome of adults with invasive pneumococcal pneumonia.

The introduction of the 7-valent pneumococcal conjugate vaccine in children has led to a change in the pattern of pneumococcal serotypes causing pneumococcal disease. The aim of this study was to compare the clinical presentation and outcome of invasive pneumococcal pneumonia (IPP) in adults between the pre and post-vaccine era. We have conducted an observational study of all adults hospitalized with IPP, from 1996 to 2001 (pre-vaccine period), and from 2005 to 2009 (post-vaccine period). Incidence, serotype distribution and clinical data were compared between both periods. A total of 653 episodes of IPP were diagnosed. The overall incidence of IPP increased from 14.2 to 17.9 cases per 100 000 population-year (p 0.003). In the post-vaccine period IPP caused by vaccine serotypes decreased (-36%; 95% CI, -52 to -15) while IPP caused by non-vaccine serotypes increased (71%; 95% CI, 41-106). IPP in the post-vaccine period was associated with higher rates of septic shock (19.1% vs. 31.1%, p <0.001). Among patients aged 50-65 years there was a trend towards a greater proportion of case-fatalities (11.6-23.5%, p 0.087). Independent risk factors for septic shock were IPP caused by serotype 3 (OR 2.38; 95% CI, 1.16-4.87) and serotype 19A (OR 6.47, 95% CI, 1.55-27). Serotype 1 was associated with a lower risk of death (OR 0.1; 95% CI, 0.01-0.78). In conclusion, the incidence of IPP in the post-vaccine period has increased in our setting, it is caused mainly by non-vaccine serotypes and it is associated with higher rates of septic shock.

[Treatment of loculated parapneumonic empyema. Video assisted thoracoscopy or fibrinolytics?]. / Tratamiento del empiema paraneumónico tabicado: ¿videotoracoscopia o fibrinolíticos?

OBJECTIVE: There is no consensus regarding the ideal treatment of loculated parapneumonic empyema (PPE). The aim of this study is to compare the effectiveness of drainage plus urokinase (DF) with video-assisted thoracoscopy (VATS). MATERIAL AND METHODS: Retrospective review. Patients admitted with a PPE between January 2001 and July 2008. Loculated empyema was diagnosed by chest ultrasound and patients were treated with DF or VATS depending on the attending surgeon. Compared variables were: post-operative stay, total hospital stay, days of tube thoracostomy, post-operative fever and treatment failure. RESULTS: One hundred and twenty one patients were admitted with the diagnosis of PPE. Seventeen patients were excluded from analysis because of simple parapneumonic effusions. Of the 104 patients included in the study, 47 were treated with urokinase and 57 with videothoracoscopy. No statistically significant differences (P>.05) were found between the median values in the DF and VATS groups for hospital stay (median 12 vs 12 days) or post-operative stay (median 9 vs 9 days). There were differences in duration of tube thoracostomy (median DF group 5 days, VATS, 4 days, P<.05) and in the post-operative fever (median 3 vs 2 days, p<0,05).Twenty two per cent of children needed a second procedure (14 patients of DF and 9 of VATS group, P=.09). CONCLUSIONS: According to our experience, the results of DF and VATS for the treatment of loculated parapneumonic empyema are similar. Although there are no statistical differences, there seems to be a higher rate of failure, with the need of more procedures in the DF group. This difference does not affect the average total hospital stay.

[The paediatrician and social problems]. / El pediatra ante los problemas sociales.

We have witnessed dramatic scientific, technological and social advances in the first decade of the XXI century. New sociological realities have enforced the rights of children, the family and gender and inequalities need to be faced under the criteria of equality in a multicultural context. It is a time to boost the overall view of childhood, to put the phonendoscope on the minor and the family, to assess the complexity of facts, such as abuse from its many facets, to shorten the distance between patients, increasing our cultural competence and to critically reflect on medicalising life as a social symptom and their possible consequences for children.