Quercetin improves and protects Calu-3 airway epithelial barrier function.

Introduction: In light of the impact of airway barrier leaks in COVID-19 and the significance of vitamin D in COVID-19 outcomes, including airway barrier protection, we investigated whether the very common dietary flavonoid quercetin could also be efficacious in supporting airway barrier function. Methods: To address this question, we utilized the widely used airway epithelial cell culture model, Calu-3. Results: We observed that treating Calu-3 cell layers with quercetin increased transepithelial electrical resistance while simultaneously reducing transepithelial leaks of 14C-D-mannitol (Jm) and 14C-inulin. The effects of quercetin were concentration-dependent and exhibited a biphasic time course. These effects of quercetin occurred with changes in tight junctional protein composition as well as a partial inhibition of cell replication that resulted in decreased linear junctional density. Both of these effects potentially contribute to improved barrier function. Quercetin was equally effective in reducing the barrier compromise caused by the pro-inflammatory cytokine TNF-α, an action that seemed to derive, in part, from reducing the elevation of ERK 1/2 caused by TNF-α. Discussion: Quercetin improved Calu-3 barrier function and reduced TNF-α-induced barrier compromise, mediated in part by changes in the tight junctional complex.

Comparative studies of the sensitivities of sparse and full geometries of Total-Body PET scanners built from crystals and plastic scintillators.

BACKGROUND: Alongside the benefits of Total-Body imaging modalities, such as higher sensitivity, single-bed position, low dose imaging, etc., their final construction cost prevents worldwide utilization. The main aim of this study is to present a simulation-based comparison of the sensitivities of existing and currently developed tomographs to introduce a cost-efficient solution for constructing a Total-Body PET scanner based on plastic scintillators. METHODS: For the case of this study, eight tomographs based on the uEXPLORER configuration with different scintillator materials (BGO, LYSO), axial field-of-view (97.4 cm and 194.8 cm), and detector configurations (full and sparse) were simulated. In addition, 8 J-PET scanners with different configurations, such as various axial field-of-view (200 cm and 250 cm), different cross sections of plastic scintillator, and multiple numbers of plastic scintillator layers (2, 3, and 4), based on J-PET technology have been simulated by GATE software. Furthermore, Siemens' Biograph Vision has been simulated to compare the results with standard PET scans. Two types of simulations have been performed. The first one with a centrally located source with a diameter of 1 mm and a length of 250 cm, and the second one with the same source inside a water-filled cylindrical phantom with a diameter of 20 cm and a length of 183 cm. RESULTS: With regards to sensitivity, among all the proposed scanners, the ones constructed with BGO crystals give the best performance ([Formula: see text] 350 cps/kBq at the center). The utilization of sparse geometry or LYSO crystals significantly lowers the achievable sensitivity of such systems. The J-PET design gives a similar sensitivity to the sparse LYSO crystal-based detectors while having full detector coverage over the body. Moreover, it provides uniform sensitivity over the body with additional gain on its sides and provides the possibility for high-quality brain imaging. CONCLUSION: Taking into account not only the sensitivity but also the price of Total-Body PET tomographs, which till now was one of the main obstacles in their widespread clinical availability, the J-PET tomography system based on plastic scintillators could be a cost-efficient alternative for Total-Body PET scanners.

Efficiency determination of J-PET: first plastic scintillators-based PET scanner.

BACKGROUND: The Jagiellonian Positron Emission Tomograph is the 3-layer prototype of the first scanner based on plastic scintillators, consisting of 192 half-metre-long strips with readouts at both ends. Compared to crystal-based detectors, plastic scintillators are several times cheaper and could be considered as a more economical alternative to crystal scintillators in future PETs. JPET is also a first multi-photon PET prototype. For the development of multi-photon detection, with photon characterized by the continuous energy spectrum, it is important to estimate the efficiency of J-PET as a function of energy deposition. The aim of this work is to determine the registration efficiency of the J-PET tomograph as a function of energy deposition by incident photons and the intrinsic efficiency of the J-PET scanner in detecting photons of different incident energies. In this study, 3-hit events are investigated, where 2-hits are caused by 511 keV photons emitted in [Formula: see text] annihilations, while the third hit is caused by one of the scattered photons. The scattered photon is used to accurately measure the scattering angle and thus the energy deposition. Two hits by a primary and a scattered photon are sufficient to calculate the scattering angle of a photon, while the third hit ensures the precise labeling of the 511 keV photons. RESULTS: By comparing experimental and simulated energy distribution spectra, the registration efficiency of the J-PET scanner was determined in the energy deposition range of 70-270 keV, where it varies between 20 and 100[Formula: see text]. In addition, the intrinsic efficiency of the J-PET was also determined as a function of the energy of the incident photons. CONCLUSION: A method for determining registration efficiency as a function of energy deposition and intrinsic efficiency as a function of incident photon energy of the J-PET scanner was demonstrated. This study is crucial for evaluating the performance of the scanner based on plastic scintillators and its applications as a standard and multi-photon PET systems. The method may be also used in the calibration of Compton-cameras developed for the ion-beam therapy monitoring and simultaneous multi-radionuclide imaging in nuclear medicine.

Multiple Perianal Ulcers Related to Use of a Hemorrhoidal Ointment With the Active Ingredients Triamcinolone Acetonide, Lidocaine, and Pentosan Polysulfate Sodium: A Series of 11 Spanish Patients. / Múltiples úlceras perianales en relación con el uso de una pomada antihemorroidal con acetónido de triamcinolona, lidocaína y pentosano polisulfato sódico como principios activos: una serie de 11 pacientes españoles.

The development of perianal ulcers related to the use of a hemorrhoidal ointment has not been reported in the literature. We describe a series of 11 patients who were treated for perianal ulcers in 10 Spanish hospitals after they used the same ointment containing the active ingredients triamcinolone acetonide, lidocaine, and pentosan polysulfate sodium. No prior or concomitant conditions suggesting an alternative cause for the condition could be identified, and after the patients stopped using the ointment, their ulcers cleared completely in 8 weeks on average. This case series shows the damage that can be caused by an over-the-counter pharmaceutical product used without medical follow-up. It also illustrates the need to ask patients with perianal ulcers about any topical agents used before the lesions appeared.

Effect of Immunosuppressive Therapy on Cardiovascular Risk Factor Prevalence in Kidney-Transplanted Children: Comparative Study.

BACKGROUND: Cardiovascular disease (CVD) is the second major cause of death in kidney-transplanted children. Cardiovascular risk factors (CVRF) prevalence after transplant may increase. The effect of immunosuppressive therapy has not been fully studied in children. The objective of the study was to measure and compare CVRF prevalence in kidney-transplanted children, depending of immunosuppressive therapy. METHODS: The study was an observational, transversal, retrospective, comparative study of pediatric patients transplanted at UMAE Hospital General Centro Medico La Raza. All patients were treated with prednisone and mycophenolic acid and any of cyclosporine, tacrolimus, or sirolimus. Demographic, clinical, and biochemical variables and immunosuppressive therapy were evaluated. We used analysis of variance, χ(2), and Fisher tests with the SPSS 18.0 statistical program. RESULTS: One hundred fifteen patients were studied. Sixty-five (56.5%) were male, and median age was 18.5 ± 2.3 years. Seventy-eight (67.2%) were transplanted from a living related donor. Prevalence of anemia and nephrotic proteinuria was significantly less in patients treated with tacrolimus. Those treated with cyclosporine had a significantly greater prevalence of increased LDL-cholesterol, increased serum phosphorus, and increased calcium-phosphorus. Those treated with tacrolimus had lower, not significant, prevalence of hypertension, hyperuricemia, hypoalbuminemia, hypercholesterolemia, hypertriglyceridemia, and low serum HDL-cholesterol than those treated with sirolimus and cyclosporine. In multivariate analysis, patients treated with cyclosporine had significantly more probability of increased phosphorus (OR, 10.65; 95% CI, 2.75-41.16, P = .001) and calcium-phosphorus (OR, 37.94; 95% CI, 3.45-416.17, P = .003) than those treated with tacrolimus. CONCLUSIONS: Patients treated with tacrolimus had less prevalence of CVRF than those treated with cyclosporine or sirolimus. Tacrolimus is the best immunosuppressive option to diminish CVRF in children after kidney transplantation.

HYPONYCHIUM ABNORMALITIES Congenital Aberrant Hyponychium vs. Acquired Pterygium Inversum Unguis vs. Acquired Reversible Extended Hyponychium: a proposed classification based on origin, pathology and outcome.

BACKGROUND: Pterygium Inversum Unguis (PIU) is a wing-like extended hyponychium associated with the absence of the distal groove. Although a rare condition, it has been described with different names, confusing both the investigator and the reader. OBJECTIVE: We propose a new nomenclature based on tissue origin and pathology, to account for these conditions. 1) Congenital Aberrant Hyponychium 2) Acquired Pterygium Inversum Unguis 3) Acquired Reversible Extended Hyponychium. MAIN OBSERVATIONS: We report a case of a 19-year-old male, with epidermal pigmentation abnormalities, who had painful fingertips of both index fingers and thumbs since he was 13. He therefore let his finger nails grow very long, minimizing painful contact with the hyponychium. Removal of the aberrant hyponychium revealed glomus bodies aggregates with increased nerve fibers. Subsequently after excision of the hyponychium, his pain was resolved. SUMMARY: Congenital, transient or permanent changes in the hyponychium should be named and classified according to tissue origin to avoid nomenclature confusion.

EGFR ligands and DNA repair genes: genomic predictors of complete response after capecitabine-based chemoradiotherapy in locally advanced rectal cancer.

Epidermal growth factor receptor (EGFR) activation by radiation leads to increased cell proliferation and acts as a radioresistance mechanism. Neoadjuvant chemoradiation is the standard of care for locally advanced rectal cancer, and to date, no biomarkers of response have been found. We analyzed polymorphisms in the EGFR and its ligands, DNA repair genes and the thymidylate synthase in 84 stages II and III rectal cancer patients treated with neoadjuvant capecitabine plus radiotherapy. The rs11942466 polymorphism in the amphiregulin (AREG) gene region was associated with a pathological complete response (ypCR) (odds ratio: 0.26; 95% confidence interval: 0.06-0.79; P=0.014). The rs11615 C>T polymorphism in the ERCC1 gene also correlated with the ypCR as no patients with a C/C genotype achieved ypCR; P=0.023. This is the first work to propose variants within the AREG and the ERCC1 genes as promising predictive biomarkers of ypCR in rectal cancer.

Intergenic polymorphisms in the amphiregulin gene region as biomarkers in metastatic colorectal cancer patients treated with anti-EGFR plus irinotecan.

In the epidermal growth factor receptor (EGFR) pathway, polymorphisms in EGFR and its ligand EGF have been studied as biomarkers for anti-EGFR treatment. However, the potential pharmacogenetic role of other EGFR ligands such as amphiregulin (AREG) and epiregulin (EREG) has not been elucidated. We studied 74 KRAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-EGFR plus irinotecan. Twenty-two genetic variants in EGFR, EGF, AREG and EREG genes were selected using HapMap database and literature resources. Three tagging single-nucleotide polymorphisms in the AREG gene region (rs11942466 C>A, rs13104811 A>G, and rs9996584 C>T) predicted disease control in the multivariate analyses. AREG rs11942466 C>A and rs9996584 C>T were also associated with overall survival (OS). The functional polymorphism, EGFR rs712829 G>T, was associated with progression-free and OS. Our findings support that intergenic polymorphisms in the AREG gene region might help to identify colorectal cancer patients that will benefit from irinotecan plus anti-EGFR therapy.

The beginnings of dermatopathology and dermatologic microbiology in Spain.

Crisóstomo Martínez from Valencia was a pioneering microscopist in 17th-century Europe. The first microscopic representations of skin in Spain appeared in an 18th-century work by Martín Martínez. Microbiology and histopathology progressed considerably in the late 19th century thanks to anatomists like Maestre de San Juan and surgeons like Federico Rubio Galí. The first Spanish pathologist to specialize in dermatology was Antonio Mendoza, a colleague of José Eugenio de Olavide at the Hospital San Juan de Dios in Madrid. Claudio Sala and Juan de Azúa also made significant contributions, including the description of pseudoepithelioma. Several disciples of Santiago Ramón y Cajal and Jorge FranciscoTello, such as Lorenzo Ruiz de Arcaute and Guillermo de la Rosa King, consolidated the dermatology laboratory, but the Civil War sent many into exile or deprived them of their professional status. Juan Rubió in Barcelona and Julio Rodríguez Puchol in Madrid were the immediate predecessors of today's dermatopathologists.

Nightlife, verbal and physical violence among young European holidaymakers: what are the triggers?

OBJECTIVES: There is an established relationship between nightlife, substance use and violence. This study investigated this relationship when people are on holiday, and explored the differences in experiences between physical and verbal violence. STUDY DESIGN: A survey of young tourists at seven airport departure areas in Southern European resorts. METHODS: Questionnaires from 6502 British and German tourists were analysed exploring demographics, violence (verbal and physical), substance use, and reasons for resort and venue selection. RESULTS: Over two-thirds of respondents reported being drunk on their holiday, 12.4% had been involved in arguments and 2.9% had been involved in fights. Logistic regression highlighted more violence amongst visitors to Mallorca [arguments: adjusted odds ratio (AOR) 2.7; fights: AOR 2.0] compared with those visiting Portugal, males (arguments: AOR 1.3; fights: AOR 1.7), those who had used illicit drugs (arguments: AOR 1.5; fights: AOR 2.9), those who had been in fights at home in the last 12 months (arguments: AOR 2.2; fights AOR 2.9), and those who had frequently been drunk abroad (arguments: AOR 2.4; fights: AOR 2.5). Those aged 16-19 years, visiting Italy or Crete, who were drunk for fewer than half of the days of their stay, and who chose bars because they were frequented by drunk people were more likely to report having an argument. Fights were associated with cannabis use and were negatively associated with choosing bars with a friendly atmosphere. Economic status or frequency of visiting bars had no relationship with arguments or fights. CONCLUSIONS: Understanding and addressing the variables involved in violence when holidaying abroad is critical in targeting appropriate health promotion and harm reduction measures.

Manifestaciones orales en pacientes VIH/SIDA asociadas a tratamiento antirretroviral y el estado inmunológico en dos fundaciones de la ciudad de Cartagena / Oral manifestations in HIV/AIDS patients associated with antiretroviral treatment and immune status in two foundations of Cartagena city

Objetivo: El objetivo de este estudio fue determinar la asociación entre las manifestaciones orales de pacientes VIH/SIDA con la terapia antirretroviral y el estado inmunológico. Metodología: Estudio de tipo transversal, en una población de 166 pacientes pertenecientes a dos fundaciones de la ciudad de Cartagena, la información se recolectó a través de un examen estomatológico intraoral teniendo en cuenta los criterios para el diagnóstico clínico de las manifestaciones orales asociadas a VIH establecidos por el Centro Colaborador de la OMS sobre las manifestaciones orales del virus de inmunodeficiencia humana, los datos como niveles de carga viral, CD4 y la terapia antirretroviral se obtuvieron de la historia clínica médica. Resultados: La prevalencia de manifestaciones orales asociadas a VIH fue del 59,5%, la candidiasis fue la manifestación oral más frecuente, con una prevalencia de 35,5%, los pacientes tratados con monoterapia presentaron menos manifestaciones orales que aquellos tratados con biterapia con valores estadísticamente significativo, OR: 0,20, IC: 0,00-0,96 (p<0,02), la candidiasis pseudomembranosa como manifestación oral asociada a VIH tiene menos probabilidades de presentarse cuando se tiene niveles de CD4 superiores a 500 cel./mm3 mostrando valores estadísticamente significativos, con un OR: 0,297, IC: 0,103-0,852 (p<0,03). Conclusión: Los pacientes tratados con monoterapia como terapéutica farmacológica antirretroviral presentaron menos manifestaciones orales que aquellos tratados con biterapia, con respecto a la candidiasis el subtipo pseudomembranosa tiene menos probabilidades de presentarse cuando se tiene niveles de CD4 superiores a 500 cel./mm3 (AU)

Objective: The aim of this study was to determine the association between oral manifestations of AIDS patients with antiretroviral therapy and their immune status. Methodology: a cross-sectional study was done in a population of 166 patients from two Cartagena's city foundations, the information was collected through an intraoral stomatological examination considering the standard for the clinical diagnosis of oral manifestations associated with AIDS established by the Collaborating Centre WHO about oral manifestations of human immunodeficiency virus, information such as viral load, CD4 and antiretroviral therapy were obtained from the medical history. Results: The prevalence of oral manifestations associated with AIDS was 59.5%, candidiasis was the most common oral manifestation with a prevalence of 35.5%, the patients treated with oral monotherapy had fewer events than those treated with combination therapy with statistically significant values, OR: 0.20, CI 0.00-0.96 (p<0.02), pseudomembranous candidiasis as oral manifestations associated with AIDS has less probabilities to occur when patients have CD4 levels above 500 cel./mm3 showing values statistically significant with a OR: 0.297, CI: 0103-0852 (p<0.03). Conclusions: Patients treated with monotherapy as antiretroviral drug therapy presented less oral manifestations than patients treated with dual therapy, about candidiasis, the subtype pseudomembranous candidiasis has less probabilities to occur when you have CD4 levels above 500 cel./mm3 (AU)

Intervención farmacéutica en pacientes quirúrgicos con alteraciones electrolíticas / Drug treatment in surgical patients with electrolyte imbalances

Objetivo Determinar cuali y cuantitativamente las alteraciones electrolíticas (relacionadas con potasio, fósforo, magnesio y calcio) en pacientes ingresados en áreas de cirugía general y gastrointestinal, el porcentaje de dichas alteraciones detectado por el equipo médico y el grado de aceptación de las recomendaciones realizadas desde el Servicio de Farmacia Hospitalaria. Método Estudio prospectivo de 7 meses. Toda alteración detectada se registró en una hoja de recogida de datos (datos personales, sala de hospitalización, tipo de alteración, detección por equipo médico, tipo de intervención farmacéutica, modo de notificación, aceptación de la intervención, fecha de corrección de la alteración, paciente en tratamiento con nutrición parenteral).Resultados Se detectaron 100 alteraciones en 66 pacientes (231 analíticas revisadas). Se realizaron un total de 78 intervenciones. La mayoría de alteraciones se debieron a hipokalemias e hipomagnesemias, siendo la hipofosfatemia la alteración más frecuente en pacientes portadores de nutrición parenteral. El grado de aceptación de la intervención farmacéutica por parte del equipo médico fue superior cuando la información fue oral (100 vs 35% escrita). Se consiguió el doble de analíticas de comprobación tras las intervenciones (RR 2,1; IC 95% 1,11-3,94, p=0,006). La aceptación de la intervención comportó una mayor proporción de resoluciones de la alteración respecto a los casos en los que no se aceptó (RR 1,5; IC 95% 1,01-2,24, p=0,04).Conclusiones Este estudio pone de manifiesto que las alteraciones electrolíticas en pacientes quirúrgicos son frecuentes y su grado de detección y seguimiento por parte del equipo médico es bajo. Por ello, el farmacéutico podría contribuir en la mejora de dichos aspectos participando en la atención a estos pacientes (AU)

Objective To qualitatively and quantitatively determine electrolyte imbalances (potassium, phosphorus, magnesium and calcium) in patients admitted for general and gastrointestinal surgery, the degree of these imbalances in percentage detected by medical staff, and the acceptance of the recommendations made by the Hospital Pharmacy Department. Method Seven-month prospective study. Any alteration detected was recorded on a data collection form (personal data, hospital ward, type of alteration, detection by medical staff, type of pharmaceutical intervention, form of notification, acceptance of the intervention, date of imbalance correction, patient receiving parenteral nutrition).Results100 imbalances were detected in 66 patients (231 analytical tests revised). A total of 78 interventions were carried out. Most changes were due to hypokalaemia and hypomagnesaemia, hypophosphataemia being the most frequent abnormality in patients receiving parenteral nutrition. The acceptance of pharmaceutical intervention was higher if the information was oral (100% vs. 35% written). Twice the number of analytical tests were performed after interventions (RR: 2.1, 95% CI: 1.11 to 3.94, P=.006). When pharmaceutical intervention was accepted there was a greater number of imbalance resolutions in comparison with those cases which did not accept (RR: 1.5, 95% CI: 1.01 to 2.24, P=.04).Conclusions This study shows that electrolyte imbalances are common in surgical patients and the level of detection and monitoring by medical staff is low. Therefore, the pharmacist could help in improving this aspect (AU)

Methotrexate consolidation treatment according to pharmacogenetics of MTHFR ameliorates event-free survival in childhood acute lymphoblastic leukaemia.

Recent advances in treatment for childhood acute lymphoblastic leukaemia (ALL) have significantly increased outcome. High-dose methotrexate (MTX) is the most commonly used regimen during the consolidation period, but the optimal dose remains to be defined. We investigated the usefulness of the MTHFR genotype to increase the MTX dosage in the consolidation phase in 141 childhood ALL patients enrolled in the ALL/SHOP-2005 protocol. We also investigated the pharmacogenetic role of polymorphisms in genes involved in MTX metabolism on therapy-related toxicity and survival. Patients with a favourable MTHFR genotype (normal enzymatic activity) treated with MTX doses of 5 g m⁻² had a significantly lower risk of suffering an event than patients with an unfavourable MTHFR genotype (reduced enzymatic activity) that were treated with the classical MTX dose of 3 g m⁻² (P=0.012). Our results indicate that analysis of the MTHFR genotype is a useful tool to optimise MTX therapy in childhood patients with ALL.

[Drug treatment in surgical patients with electrolyte imbalances]. / Intervención farmacéutica en pacientes quirúrgicos con alteraciones electrolíticas.

OBJECTIVE: To qualitatively and quantitatively determine electrolyte imbalances (potassium, phosphorus, magnesium and calcium) in patients admitted for general and gastrointestinal surgery, the degree of these imbalances in percentage detected by medical staff, and the acceptance of the recommendations made by the Hospital Pharmacy Department. METHOD: Seven-month prospective study. Any alteration detected was recorded on a data collection form (personal data, hospital ward, type of alteration, detection by medical staff, type of pharmaceutical intervention, form of notification, acceptance of the intervention, date of imbalance correction, patient receiving parenteral nutrition). RESULTS: 100 imbalances were detected in 66 patients (231 analytical tests revised). A total of 78 interventions were carried out. Most changes were due to hypokalaemia and hypomagnesaemia, hypophosphataemia being the most frequent abnormality in patients receiving parenteral nutrition.The acceptance of pharmaceutical intervention was higher if the information was oral (100% vs. 35% written). Twice the number of analytical tests were performed after interventions (RR: 2.1, 95% CI: 1.11 to 3.94, P=.006). When pharmaceutical intervention was accepted there was a greater number of imbalance resolutions in comparison with those cases which did not accept (RR: 1.5, 95% CI: 1.01 to 2.24, P=.04). CONCLUSIONS: This study shows that electrolyte imbalances are common in surgical patients and the level of detection and monitoring by medical staff is low. Therefore, the pharmacist could help in improving this aspect.

[History of Actas Dermo-Sifiliográficas, part I: 1909-1959]. / Historia de Actas Dermo-Sifiliográficas (I): 1909-1959.

Actas Dermo-Sifiliográficas was born in May 1909. At first, issues appeared in step with the academic year, but publication began to follow the calendar year in 1957. Volume 18 was skipped in 1926-7 in an effort to correct confusion in the numbering of volumes and pages of earlier issues. October 1928 saw the journal grow from 6 issues per year to 9. Although the Spanish Civil War brought publication to a halt during the 1936-7 academic year, Actas Dermo-Sifiliográficas was one of the first Spanish scientific journals to recover from the conflict. The initial print run of 100 copies was increased to 700 after the war. The content evolved over time: while originally conceived to provide a strict account of sessions of the Spanish Academy of Dermatology and Venereology (AEDV) -originally known as the Spanish Academy of Dermatology and Syphilology- the journal gradually came to include review articles, case reports, a section summarizing the content of international journals, news and various other types of writing. The editorial board and the association's board of directors were one and the same for many years. According to the earliest charter, the editor-in-chief was also the president of the association and the associate editor was the association's vice-president. The subjects of articles provide a faithful portrait of how the specialty has changed. Syphilis, a main concern before the introduction of penicillin in the 1940s, was sidelined afterwards. The appearance of 20th-century pharmaceuticals such as salvarsan, sulfa drugs, thiazides, and corticosteroids were soon reflected in the number of articles describing their use. Certain original contributions by Spanish authors to international dermatology first appeared in Actas Dermo-Sifiliográficas. Examples are Azúa's description of pseudoepithelioma and Covisa and Bejarano's of chancriform pyoderma. Volume 50 (1959), which included accounts of the 50th anniversary of the association and the journal, closed with a biography of Enrique Álvarez Sainz de Aja, the only founding member still living at that time.

A genotype-directed phase I-IV dose-finding study of irinotecan in combination with fluorouracil/leucovorin as first-line treatment in advanced colorectal cancer.

BACKGROUND: Infusional fluorouracil/leucovorin (FU/LV) plus irinotecan (FOLFIRI) is one of the standard first-line options for patients with metastatic colorectal cancer (mCRC). Irinotecan is converted into 7-ethyl-10-hydroxycamptothecin (SN-38) by a carboxylsterase and metabolised through uridine diphosphate glucuronosyl transferase (UGT1A1). The UGT1A1*28 allele has been associated with the risk of developing severe toxicities. The present trial was designed to define the maximum tolerated dose according to UGT1A1 genotype. This report focuses on the results of tolerance to different escalated doses of FOLFIRI first-line of chemotherapy. PATIENTS AND METHODS: Patients undergoing first-line treatment for mCRC and eligible for treatment with FOLFIRI were classified according to UGT1A1 genotype. A total of 94 patients were eligible for dose escalation of irinotecan. The starting dose of biweekly irinotecan was 180 mg m(-2) for the *1/*1, 110 mg m(-2) for the *1/*28 and 90 mg m(-2) for the *28/*28 genotypes. RESULTS: The dose of irinotecan was escalated to 450 mg m(-2) in patients with the *1/*1 genotype, to 390 mg m(-2) in those with the *1/*28 genotype and to 150 mg m(-2) in those with the *28/*28 genotype. Neutropenia and diarrhoea were the most common grade 3 or 4 toxicities. CONCLUSIONS: Our results demonstrated that the recommended dose of 180 mg m(-2) for irinotecan in FOLFIRI is considerably lower than the dose that can be tolerated for patients with the UGT1A1 *1/*1 and *1/*28 genotypes. The maximum tolerable dose (MTD) in patients with a high-risk UGT1A1 *28/*28 genotype is 30% lower than the standard dose of 180 mg m(-2).

[Favorable outcome of acute respiratory failure caused by H1N1 virus infection in critical patients]. / Evolución favorable de insuficiencia respiratoria aguda por gripe A (H1N1) en pacientes críticos.

OBJECTIVE: To describe clinical features, treatment, complications, and outcomes in cases of acute respiratory distress syndrome (ARDS) caused by H1N1 virus infection treated in an anesthesia department's recovery unit. MATERIALS AND METHODS: Patients were those admitted to our recovery unit with H1N1 virus infection confirmed by reverse transcription polymerase chain reaction, nasopharyngeal swabs, and/or bronchial aspirates. RESULTS: From August to December 2009, we admitted 8 patients (mean age, 43 [range 24-46] years) to the recovery unit. Six were men, three were of Roma origin, and 50% had concomitant diseases. Mean (SD) time from symptom onset to admittance to the recovery unit was 3.25 (1.6) days. Four had received broad-spectrum antibiotics during the last month. Six had primary viral pneumonia, 1 had secondary bacterial pneumonia and 1 had exacerbated chronic obstructive pulmonary disease. Three had bacterial coinfection, and 4 developed multiple organ dysfunction syndrome and ARDS, requiring mechanical ventilation (5.75 [3.10] days) and vasopressors (4.25 [3.40] days). The mean ratio of PaO2 to the inspired oxygen fraction at admittance was 93.8 (31.0) and the mean positive end-expiratory pressure applied was 14.5 (4.2) cm H2O. Oseltamivir was administered (150 mg/12 h) with a mean delay of 3.88 (1.64) days. Additional inhaled zanamivir was administered on day 7 to a patient with a positive viral culture. Antibiotics were prescribed following the guidelines of the American Thoracic Society and Infectious Diseases Society of America for community-acquired pneumonia (50% of the cases) and healthcare-associated pneumonia (50%). Seven subjects received 1 mg x kg(-1) x day(-1) of methylprednisolone. Patients with mechanical ventilation required continuous insulin infusion (maximum daily dosage, 87 [50.3] IU) to maintain blood glucose levels between 80 and 150 mg x dL(-1). Patients under mechanical ventilation achieved a negative net fluid balance. All patients survived and were discharged from the recovery unit in 7.38 (4.83) days (range, 2-16 days) and subsequently discharged home in 13.25 (7.74) days (range, 6-27 days). All were alive 60 days after discharge. CONCLUSION: In this series of critically ill patients with H1N1 virus infection that was initially life-threatening, all responded favorably to conventional treatment and could be discharged.

Evolución favorable de insuficiencia respiratoria aguda por gripe A (H1N1) en pacientes críticos / Favorable outcome of acute respiratory failure caused by H1N1 virus infection in critical patients

Objetivo: Describir las características clínicas, el tratamiento, las complicaciones y la evolución de los pacientes ingresados en una unidad de reanimación con insuficiencia respiratoria aguda por gripe A (H1N1). Material y métodos: Se analizaron los enfermos ingresados en nuestra unidad de reanimación en los que se confirmó una infección por virus de la gripe A (H1N1) utilizando la prueba de reacción en cadena de la polimerasa en transcripción reversa (RT-PCR) en las muestras obtenidas a nivel nasofaríngeo y/o aspirado bronquial. Resultados: Desde agosto a diciembre del año 2009 ingresaron 8 pacientes con una edad media de 43 años (rango 24–61), 6 fueron varones, 3 de etnia gitana, con enfermedades asociadas en un 50%. El tiempo desde el inicio de los síntomas hasta el ingreso en la unidad de reanimación fue de 3,25 ± 1,6 días. Cuatro habían recibido antibióticos de amplio espectro en el último mes. Seis tenían neumonía viral primaria, uno neumonía bacteriana secundaria y otro exacerbación de una obstrucción crónica al flujo aéreo. Tres presentaban coinfección bacteriana, 4 desarrollaron fallo multiorgánico y síndrome de dificultad respiratoria aguda necesitando ventilación mecánica (5,75 ± 3,10 días) y vasopresores (4,25 ± 3,40 días). El cociente PaO2/FiO2 de ingreso fue de 93,8 ± 31,0 y la presión positiva al final de la espiración (PEEP) media en el primer día fue de 14,5 ± 4,2 cm H2O. Se administró 150 mg/12 horas de oseltamivir con un retraso promedio de 3,88 ± 1,64 días y se añadió zanamivir inhalado a un paciente con cultivo viral positivo al 7º día. Los antibióticos se prescribieron siguiendo las recomendaciones de la IDSA/ATS para la neumonía adquirida en la comunidad (50%) y la neumonía asociada al cuidado sanitario (50%). Siete recibieron 1 mg kg –1 día–1 de metilprednisolona. Los pacientes con ventilación mecánica necesitaron de infusión continua de insulina (dosis máxima/día 87 ± 50,3 UI) para mantener los valores de glucemia entre 80 y 150 mg dL–1. Se consiguió un balance hídrico neto negativo en los pacientes con ventilación mecánica. Todos sobrevivieron y fueron dados de alta de la unidad de reanimación en 7,38 ± 4,83 días (rango 2–16) y posteriormente a su domicilio en 13,25 ± 7,74 días (rango 6–27) que permanecieron todos vivos a los 60 días. Conclusión: En nuestra serie los pacientes críticos con gripe A (H1N1) inicialmente presentan un riesgo elevado de muerte, pero responden favorablemente a los tratamientos convencionales y pueden ser dados de alta a su domicilio (AU)

Objective: To describe clinical features, treatment, complications, and outcomes in cases of acute respiratory distress syndrome (ARDS) caused by H1N1 virus infection treated in an anesthesia department’s recovery unit. Materials and methods: Patients were those admitted to our recovery unit with H1N1 virus infection confirmed by reverse transcription polymerase chain reaction, nasopharyngeal swabs, and/or bronchial aspirates. Results: From August to December 2009, we admitted 8 patients (mean age, 43 [range 24–46] years) to the recovery unit. Six were men, three were of Roma origin, and 50% had concomitant diseases. Mean (SD) time from symptom onset to admittance to the recovery unit was 3.25 (1.6) days. Four had received broad-spectrum antibiotics during the last month. Six had primary viral pneumonia, 1 had secondary bacterial pneumonia and 1 had exacerbated chronic obstructive pulmonary disease. Three had bacterial coinfection, and 4 developed multiple organ dysfunction syndrome and ARDS, requiring mechanical ventilation (5.75 [3.10] days) and vasopressors (4.25 [3.40] days). The mean ratio of PaO2 to the inspired oxygen fraction at admittance was 93.8 (31.0) and the mean positive end-expiratory pressure applied was 14.5 (4.2) cm H2O. Oseltamivir was administered (150 mg/12 h) with a mean delay of 3.88 (1.64) days. Additional inhaled zanamivir was administered on day 7 to a patient with a positive viral culture. Antibiotics were prescribed following the guidelines of the American Thoracic Society and Infectious Diseases Society of America for community-acquired pneumonia (50% of the cases) and healthcare-associated pneumonia (50%). Seven subjects received 1 mg•kg–1•day–1 of methylprednisolone. Patients with mechanical ventilation required continuous insulin infusion (maximum daily dosage, 87 [50.3] IU) to maintain blood glucose levels between 80 and 150 mg•dL–1. Patients under mechanical ventilation achieved a negative net fluid balance. All patients survived and were discharged from the recovery unit in 7.38 (4.83) days (range, 2–16 days) and subsequently discharged home in 13.25 (7.74) days (range, 6–27 days). All were alive 60 days after discharge. Conclusion: In this series of critically ill patients with H1N1 virus infection that was initially life-threatening, all responded favorably to conventional treatment and could be discharged (AU)