Impact of NADPH oxidase functional polymorphisms in acute myeloid leukemia induction chemotherapy.

Efficacy and toxicity of anthracycline treatment in acute myeloid leukemia (AML) is mediated by reactive oxygen species (ROS). NADPH oxidase is the major endogenous source of ROS and a key mediator of oxidative cardiac damage. The impact of NADPH oxidase polymorphisms (CYBA:rs4673, NCF4:rs1883112, RAC2:rs13058338) was evaluated in 225 adult de novo AML patients. Variant alleles of NCF4 and RAC2 were related to higher complete remission (P=0.035, P=0.016), and CYBA homozygous variant showed lower overall survival with recessive model (P=0.045). Anthracycline-induced cardiotoxicity was associated to NCF4 homozygous variant (P=0.012) and CYBA heterozygous genotype (P=0.027). Novel associations were found between variant allele of CYBA and lower lung and gastrointestinal toxicities, and a protective effect in nephrotoxicity and RAC2 homozygous variant. Moreover, RAC2 homozygous variant was related to delayed thrombocytopenia recovery. This study supports the interest of NADPH oxidase polymorphisms regarding efficacy and toxicity of AML induction therapy, in a coherent integrated manner.

Recommendations of the Working Groups from the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) for the management of adult critically ill patients. / Recomendaciones para el tratamiento de los pacientes críticos de los Grupos de Trabajo de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC).

The standardization of the Intensive Care Medicine may improve the management of the adult critically ill patient. However, these strategies have not been widely applied in the Intensive Care Units (ICUs). The aim is to elaborate the recommendations for the standardization of the treatment of critical patients. A panel of experts from the thirteen working groups (WG) of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) was selected and nominated by virtue of clinical expertise and/or scientific experience to carry out the recommendations. Available scientific literature in the management of adult critically ill patients from 2002 to 2016 was extracted. The clinical evidence was discussed and summarised by the experts in the course of a consensus finding of every WG and finally approved by the WGs after an extensive internal review process that was carried out between December 2015 and December 2016. A total of 65 recommendations were developed, of which 5 corresponded to each of the 13 WGs. These recommendations are based on the opinion of experts and scientific knowledge, and are intended as a guide for the intensivists in the management of critical patients.

A systematic review and meta-analysis of the impact of WT1 polymorphism rs16754 in the effectiveness of standard chemotherapy in patients with acute myeloid leukemia.

The polymorphism rs16754 of the WT1 gene has been described as a possible prognostic marker in different acute myeloid leukemia (AML) cohorts; however, it is not supported by all the studies. We performed the first meta-analysis evaluating the effect of this polymorphism upon the effectiveness of standard AML therapy. Fourteen cohort studies were included (3618 patients). Patients with the variant allele showed a significant higher overall survival (OS) at 5 years (OR:1.24, 95% CI: 1.06-1.45, P=0.007, with dominant model). WT1 did not influence complete remission, but a higher disease-free survival was observed with the variant allele. In the subgroup analysis, Caucasians, pediatric and patients treated with idarubicin and etoposide carrying the variant allele showed consistent results in OS, whereas patients with cytogenetically normal AML did not show differences. To verify the effect of this polymorphism upon other outcomes, studies in larger and multiracial populations are needed.

Mortality prediction using TRISS methodology in the Spanish ICU Trauma Registry (RETRAUCI).

OBJECTIVES: To validate Trauma and Injury Severity Score (TRISS) methodology as an auditing tool in the Spanish ICU Trauma Registry (RETRAUCI). DESIGN: A prospective, multicenter registry evaluation was carried out. SETTING: Thirteen Spanish Intensive Care Units (ICUs). PATIENTS: Individuals with traumatic disease and available data admitted to the participating ICUs. INTERVENTIONS: Predicted mortality using TRISS methodology was compared with that observed in the pilot phase of the RETRAUCI from November 2012 to January 2015. Discrimination was evaluated using receiver operating characteristic (ROC) curves and the corresponding areas under the curves (AUCs) (95% CI), with calibration using the Hosmer-Lemeshow (HL) goodness-of-fit test. A value of p<0.05 was considered significant. MAIN VARIABLES OF INTEREST: Predicted and observed mortality. RESULTS: A total of 1405 patients were analyzed. The observed mortality rate was 18% (253 patients), while the predicted mortality rate was 16.9%. The area under the ROC curve was 0.889 (95% CI: 0.867-0.911). Patients with blunt trauma (n=1305) had an area under the ROC curve of 0.887 (95% CI: 0.864-0.910), and those with penetrating trauma (n=100) presented an area under the curve of 0.919 (95% CI: 0.859-0.979). In the global sample, the HL test yielded a value of 25.38 (p=0.001): 27.35 (p<0.0001) in blunt trauma and 5.91 (p=0.658) in penetrating trauma. TRISS methodology underestimated mortality in patients with low predicted mortality and overestimated mortality in patients with high predicted mortality. CONCLUSIONS: TRISS methodology in the evaluation of severe trauma in Spanish ICUs showed good discrimination, with inadequate calibration - particularly in blunt trauma.

Epidemiology of severe trauma in Spain. Registry of trauma in the ICU (RETRAUCI). Pilot phase. / Epidemiología del trauma grave en España. REgistro de TRAuma en UCI (RETRAUCI). Fase piloto.

OBJECTIVE: To describe the characteristics and management of severe trauma disease in Spanish Intensive Care Units (ICUs). Registry of trauma in the ICU (RETRAUCI). Pilot phase. DESIGN: A prospective, multicenter registry. SETTING: Thirteen Spanish ICUs. PATIENTS: Patients with trauma disease admitted to the ICU. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Epidemiology, out-of-hospital attention, registry of injuries, resources utilization, complications and outcome were evaluated. RESULTS: Patients, n=2242. Mean age 47.1±19.02 years. Males 79%. Blunt trauma 93.9%. Injury Severity Score 22.2±12.1, Revised Trauma Score 6.7±1.6. Non-intentional in 84.4% of the cases. The most common causes of trauma were traffic accidents followed by pedestrian and high-energy falls. Up to 12.4% were taking antiplatelet medication or anticoagulants. Almost 28% had a suspected or confirmed toxic influence in trauma. Up to 31.5% required an out-of-hospital artificial airway. The time from trauma to ICU admission was 4.7±5.3hours. At ICU admission, 68.5% were hemodynamically stable. Brain and chest injuries predominated. A large number of complications were documented. Mechanical ventilation was used in 69.5% of the patients (mean 8.2±9.9 days), of which 24.9% finally required a tracheostomy. The median duration of stay in the ICU and in hospital was 5 (range 3-13) and 9 (5-19) days, respectively. The ICU mortality rate was 12.3%, while the in-hospital mortality rate was 16.0%. CONCLUSIONS: The pilot phase of the RETRAUCI offers a first impression of the epidemiology and management of trauma disease in Spanish ICUs.

Influence of ABCB1 polymorphisms upon the effectiveness of standard treatment for acute myeloid leukemia: a systematic review and meta-analysis of observational studies.

The ABCB1 gene encodes for P-glycoprotein (P-gp), an efflux pump for a variety of xenobiotics. The role of ABCB1 polymorphisms in acute myeloid leukemia (AML) outcomes of standard chemotherapy (cytarabine plus anthracyclines) remains controversial. A systematic search was made of studies evaluating the association between ABCB1 polymorphisms 1236C>T, 2677G>T/A and 3435C>T and effectiveness variables. We found seven cohort studies (1241 patients) showing a significantly higher overall survival (OS) among carriers of the variant allele of 1236C>T at year 4 (odds ratio (OR): 1.47, 95% confidence interval (CI): 1.07-2.01), 2677G>T/A at years 4-5 (OR: 1.37, 95% CI: 1.01-1.86) and 3435C>T at years 3 (OR: 1.41, 95% CI: 1.03-1.94) and 4-5 (OR: 1.42, 95% CI: 1.05-1.91). In the subgroup analysis according to ethnicity, Caucasians carrying variant allele showed consistent results in OS. ABCB1 influence upon complete remission could not be demonstrated. Future studies based on larger populations and multiethnic groups should help clarify the effect of P-gp polymorphisms upon other outcomes.

[Cervix adenocarcinoma in a virgin patient with negative human papillomavirus]. / Adenocarcinoma de cérvix en una paciente virgen con virus del papiloma humano negativo.

Cervical cancer in virgin women is extremely rare. We present the case of a 36-year-old patient without any type of sexual contact with sensa- tion of lump in external genitalia referring only irregular bleeding in the previous two months, finding in vaginal examination an indurated mass in vaginal introitus with result in the biopsy of adenosquamous adenocarcinoma. The evolution of the tumor was very aggressive in spite of trying palliative chemotherapy, and patient died two months after of diagnosis with lung, liver and brain metastases. Cervical human papil- lomavirus testing was negative. What unusual of these cases does not justify the cytology as the only method of screening for cervical cancer.

Quality of trauma care and trauma registries.

Traumatic disease is a major public health concern. Monitoring the quality of services provided is essential for the maintenance and improvement thereof. Assessing and monitoring the quality of care in trauma patient through quality indicators would allow identifying opportunities for improvement whose implementation would improve outcomes in hospital mortality, functional outcomes and quality of life of survivors. Many quality indicators have been used in this condition, although very few ones have a solid level of scientific evidence to recommend their routine use. The information contained in the trauma registries, spread around the world in recent decades, is essential to know the current health care reality, identify opportunities for improvement and contribute to the clinical and epidemiological research.

Caspofungin for the treatment of invasive fungal disease in hematological patients (ProCAS Study).

Caspofungin is an echinocandin with proven efficacy in invasive candidiasis (IC) and invasive aspergillosis (IA). This multicenter, prospective, non-comparative, observational ProCAS study was aimed to assess the effectiveness and safety of caspofungin in adult hematological patients with IC or IA under everyday clinical conditions. Favorable outcomes included complete and partial responses on the last day of caspofungin therapy. Safety was assessed up to 14 days post-caspofungin. A total of 115 patients (69 male) with a median age of 52 years (range, 23-78 years) were analyzed. Underlying disease was acute myeloid leukemia in 45 patients (39%), and 21 (18%) were allogeneic stem cell transplant recipients. Thirty-four (29.5%) patients had a diagnosis of IA and 26 (22.6%) had IC (candidemia). The median duration of caspofungin therapy was 14 days (range, 1-100). The overall favorable response rate was 77% (20/26) for patients with IC (69% first-line) and 79% (27/34) for those with IA. Antifungal therapy with caspofungin was generally well tolerated, only two (1.7%) patients having a non-serious drug-related adverse reaction. These results suggest that caspofungin, either alone or in combination, should be considered an effective and safe option for the treatment of invasive mycoses in patients with severe hematological disorders.

Cross-sectional validation study of patient-reported outcomes in patients with paroxysmal nocturnal haemoglobinuria.

BACKGROUND: Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired, clonal haemopoietic stem cell disorder that causes chronic intravascular haemolysis, increases the risk of thrombosis and results in significant patient morbidity and mortality. The symptoms of PNH may have a major impact on patient quality of life. AIMS: To assess patient fatigue and health-related quality of life in 29 patients with PNH using the Functional Assessment of Chronic Illness Therapy Fatigue subscale version 4 (FACIT-Fatigue) and the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-C30, version 3 (EORTC QLQ-C30). METHODS: Following completion of the questionnaires, patients were interviewed to assess the validity, clarity, relevance and comprehensiveness of the assessments. RESULTS: Overall, patients considered both the FACIT-Fatigue and EORTC QLQ-C30 instruments to be relevant and adequate in assessing the level of PNH-associated fatigue and other quality-of-life measures. The FACIT-Fatigue questionnaire was considered to be clear and to comprehensively cover PNH-related fatigue. The EORTC QLQ-C30 instrument was considered to be easy to understand, but of an overall lower relevance, although some differences between countries were observed. Patients suggested additional questions that could be incorporated into future EORTC QLQ-C30 versions to make it more relevant to PNH. CONCLUSIONS: This study confirms the validity of the FACIT-Fatigue and the EORTC QLQ-C30 questionnaires in this patient population and their routine use should be considered in the management of patients with PNH.

[In vitro generation of a human bladder wall substitute by tissue engineering]. / Generación in vitro de un sustituto de pared vesical humana obtenido mediante ingeniería tisular.

INTRODUCTION: Certain urological congenital conditions, such as bladder exstrophy and acquired conditions such as trauma and tumors may require the use of different tissues like small bowel, sigmoid colon or stomach for bladder reconstruction. However, these tissues are often associated to important complications. The aim of this study is to develop a novel substitute of the human bladder wall by tissue engineering. MATERIAL AND METHODS: We first generated primary cell cultures of epithelial and stromal bladder mucosa cells from small tissue biopsies of human bladder by using enzymatic methods based on trypsin-EDTA and collagenase I. Then, a three-dimensional substitute of the bladder mucosa was generated using fibrin-agarose biomaterials. The analysis of the tissue substitutes was carried out at day 14th of development by histological examination of samples stained with hematoxylin-eosin. RESULTS: The use of enzymatic digestion methods allowed us to efficiently generate primary cell cultures of the human bladder epithelial and stromal cells. The proliferation rate was higher in stromal cells as compared to epithelial cells. Once the bladder mucosa substitutes were generated, a good biocompatibility of the stromal and epithelial cells into the biomaterial was found. The histological structure of the bladder wall substitutes was analogue to that of the native human bladder mucosa. CONCLUSIONS: The bladder mucosa substitute generated by tissue engineering showed structural and histological similarities with the native human bladder tissues and open the door to the future therapeutic use of these bioengineered tissues.

[Multi-tissue donor: a reachable option]. / El donante multitejido: una opción a nuestro alcance.

The clinical use of human tissues is a therapeutic reality in many diseases, observing a spectacular increase in their demand in recent years. This has also generated an increase in the demand for donors which, in regarding to obtaining tissues, is not limited to brain death donors. Consequently, tissues obtained from cardiorespiratory arrest donors must be promoted in our hospitals. With this purpose, we present our experience in the last five years and the mechanisms we used to reach these goals. During this period, an awareness and health care staff information campaign was carried out in the Emergency and Hemodynamic areas. The next step will be to extend this campaign to the rest of the hospital staff. We believe that the mechanisms needed to obtain hospital staff collaboration in the detection of multi-tissue donors is to offer updated information on the indications and therapeutic advantages of clinical use of human tissues, favoring hospital awareness on this subject and therefore the detection of potential donors.

[Recommendations of the Working Groups from the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) for the management of adult critically ill patients in the coronavirus disease (COVID-19)]. / Recomendaciones de «hacer¼ y «no hacer¼ en el tratamiento de los pacientes críticos ante la pandemia por coronavirus causante de COVID-19 de los Grupos de Trabajo de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC).

On March 11, 2020, the Director-General of the World Health Organization (WHO) declared the disease caused by SARS-CoV-2 (COVID-19) as a pandemic. The spread and evolution of the pandemic is overwhelming the healthcare systems of dozens of countries and has led to a myriad of opinion papers, contingency plans, case series and emerging trials. Covering all this literature is complex. Briefly and synthetically, in line with the previous recommendations of the Working Groups, the Spanish Society of Intensive, Critical Medicine and Coronary Units (SEMICYUC) has prepared this series of basic recommendations for patient care in the context of the pandemic.

[Contingency plan for the intensive care services for the COVID-19 pandemic]. / Plan de contingencia para los servicios de medicina intensiva frente a la pandemia COVID-19.

In January 2020, the Chinese authorities identified a new virus of the Coronaviridae family as the cause of several cases of pneumonia of unknown aetiology. The outbreak was initially confined to Wuhan City, but then spread outside Chinese borders. On 31 January 2020, the first case was declared in Spain. On 11 March 2020, The World Health Organization (WHO) declared the coronavirus outbreak a pandemic. On 16 March 2020, there were 139 countries affected. In this situation, the Scientific Societies SEMICYUC and SEEIUC have decided to draw up this Contingency Plan to guide the response of the Intensive Care Services. The objectives of this plan are to estimate the magnitude of the problem and identify the necessary human and material resources. This is to provide the Spanish Intensive Medicine Services with a tool to programme optimal response strategies.