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Resumen La mayoría de los casos de inflamación diverticular son leves y solo requieren tratamiento médico con dieta líquida y antibióticos. Hasta hace poco, este tratamiento requería ingreso hospitalario con los consiguientes costes. El tratamiento ambulatorio de estos pacientes con diverticulitis no complicada ha demostrado ser eficaz y seguro. El objetivo de esta revisión es describir el tratamiento ambulatorio con antibiótico oral y los resultados publicados.

Resumen Tras un episodio de diverticulitis aguda la realización de una colonoscopia de rutina ha sido defendida en las guías de práctica clínica de numerosas sociedades. Sin embargo, en los últimos años en contraposición a esto, numerosos estudios han intentado demostrar que no existe esta necesidad en todos los casos. ya que la incidencia de adenomas de alto grado (AA) y cáncer colorrectal (CCR) en la diverticulitis aguda no complicada es bajo y prácticamente similar al que encontramos en la población sometida a programas de screening, mientras que sería necesaria en pacientes con diverticulitis aguda complicada.

Resumen La enfermedad diverticular es uno de los trastornos gastrointestinales más frecuentes en el mundo occidental, y su presentación aguda se desarrollará en un 10-25% de los pacientes diagnosticados. Se presenta, a continuación, una revisión de conjunto sobre el tratamiento laparoscópico actual de la diverticulitis aguda, así como del lavado y drenaje laparoscópico.

The objective of this study was to explore the relationship between sociodemographic factors and fear of COVID-19 in a Cuban population. A web-based study with a cross-sectional design was conducted. The sample comprised 1145 participants. To explore fear, the Fear of COVID-19 Scale was used. Our results suggest that women were more likely to experience medium to high levels fear compared to men. Additionally, knowing a person positive to COVID-19 significantly increases fear levels in Cuban participants.

OBJECTIVES Few data regarding follow-up of patients after COVID-19 discharge are available. We aim to describe the long-term outcomes of survivors of hospitalization for COVID-19 followed up first at an outpatient facility and subsequently by telephone. METHODS Observational prospective study conducted at a tertiary general hospital. Clinical and radiological progression was assessed and data recorded on a standardized reporting form. Patients were divided into three groups according to PaO2/FiO2 at hospitalization: PaO2/FiO2 > 300, PaO2/FiO2 300-200 and PaO2/FiO2 < 200. A logistic multivariate regression model was performed to identify factors associated with persistence of symptoms. RESULTS Facility follow-up: 302 patients were enrolled. Median follow-up was 45 days after discharge; 78% (228/294) of patients had COVID-19-related symptoms (53% asthenia, 56% respiratory symptoms) and 40% (122/302) had residual pulmonary radiographic lesions. PaO2/FiO2 300 was associated with resolution of chest radiographic lesions; OR = 0.56 (0.42 to 0.74), (p, Graphical abstract Image 1

Resumen El soporte respiratorio no invasivo (SRNI) comprende 2 modalidades de tratamiento, la ventilacion meca-nica no invasiva (VMNI) y la terapia de alto flujo con canulas nasales (TAFCN) que se aplican en pacientes adultos, pediatricos y neonatales con insuficiencia respiratoria aguda (IRA). Sin embargo, el grado de acuerdo entre las distintas especialidades sobre el beneficio de estas tecnicas en diferentes escenarios clinicos es controvertido. El objetivo del presente consenso fue elaborar una serie de recomendaciones de buena practica clinica para la aplicacion de soporte no invasivo en pacientes con IRA, avaladas por todas las sociedades cientificas involucradas en el manejo del paciente adulto y pediatrico/neonatal con IRA. Para ello se contacto con las diferentes sociedades implicadas, quienes designaron a su vez a un grupo de 26 profesionales con suficiente experiencia en su aplicacion. Se realizaron 3 reuniones presenciales para consensuar las recomendaciones (hasta un total de 71) fundamentadas en la revision de la literatura y en la actualizacion de la evidencia disponible en relacion con 3 categorias: indicaciones, monitorizacion yseguimiento del SRNI. Finalmente, se procedio a votacion telematica de cada una de las recomendaciones, por parte de los expertos de cada sociedad cientifica implicada. Para la clasificacion del grado de acuerdo se opto por un sistema analogico de clasificacion facil e intuitivo de usar, y que expresara con claridad si el procedimiento relacionado con el SRNI debia hacerse, podia hacerse o no debia hacerse.

Purpose To test the primary hypothesis that a CPR video will reduce ICU patients' surrogates' anxiety when deciding code status, as measured by the Hamilton Anxiety Rating (HAM-A) Scale, as compared to the no video group. Materials and methods This is a prospective randomized control trial. Twenty-seven ICU patients' surrogates were enrolled in the study after receiving an ICU team-led code status discussion. After the enrollment, twelve surrogates were randomized to the video group and fifteen to the no video group. The primary outcome of anxiety was quantified using the HAM-A Scale. Demographic information, clinical data, and patients' provenance information (Home vs. Not Home) were collected. The patients' severity of illness was calculated using the Sequential Organ Failure Assessment (SOFA) Score. Results The HAM-A score in the video group was 5.65 points lower than in the no video group ([β = −5.65, 95% CI −11.12 −0.18] P = 0.04). The statistically significant difference was maintained when adjusting for patients' SOFA Score and patients' provenance (P = 0.03). Conclusion CPR video used to supplement ICU team-led code status discussions reduced surrogates' anxiety, as compared to no video. Trial Registration: ClinicalTrials.gov Identifier NCT03630965 .

Made available in DSpace on 2021-06-25T11:50:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-25 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) National Centre for Energy and Materials Research (CNPEM) Brazilian Nanotechnology National Laboratory (LNNano) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) NaTaO3 is a promising material for the production of hydrogen fuel via photocatalytic water splitting, although the wide band gap prevents its application with solar light. In order to overcome this issue, bismuth doping has been proposed as a method for band gap narrowing by introducing midgap electron states. In this work, Bi-doped NaTaO3 nanocubes were synthesized through a facile molten salt method and the photocatalysts exhibit hydrogen evolution under simulated sunlight irradiation (AM 1.5G). X-ray diffraction, Raman, and UV-vis spectra suggest that the incorporation of Bi3+ at the Ta-site induces band gap narrowing, in addition to a structural transition, as the orthorhombic perovskite lattice becomes pseudocubic at low dopant concentrations (0.5-4 mol %). The optimal photocatalytic activity of 3 mol % Bi-doped NaTaO3 may be a result of the simultaneous presence of the pseudocubic lattice and the narrowed band gap of 3.6 eV, which in turn promote the absorption of ultraviolet light from the AM 1.5G irradiation source. Theoretical simulations based on density functional theory were used in conjunction with the experimental results to present in detail the additional contribution of the doped pseudocubic phase in the system. Furthermore, 3 mol % Bi-doped NaTaO3 was loaded with Ni cocatalysts by magnetron sputtering deposition, leading to enhanced and stable H-2 production rates for more than 100 h of reaction. Univ Sao Paulo, Sao Carlos Inst Phys, BR-13560970 Sao Carlos, SP, Brazil Sao Paulo State Univ, Modeling & Mol Simulat Grp, BR-17030360 Bauru, SP, Brazil Univ Fed Pelotas, CCAF, PPGCEM CDTec, BR-96010610 Pelotas, RS, Brazil Sao Paulo State Univ, Modeling & Mol Simulat Grp, BR-17030360 Bauru, SP, Brazil FAPESP: 2017/18716-3 FAPESP: 2018/25705-0 Brazilian Nanotechnology National Laboratory (LNNano): TEM-C1-27122-F FAPESP: 2019/08928-9 CNPq: 432242/2018-0

Spasticity is a motor disorder characterised by an increase in muscle tone that appears as a consequence of a central nervous system disorder, leading to deficit and disability and impairing quality of life. In acquired adult brain damage, spasticity is a severe and frequent problem, appearing in 20-30% of patients with stroke and in 13-20% of patients with moderate-severe traumatic brain injury. The main objective of this study was to perform a systematic review of the treatments used in spasticity in adult patients with acquired brain damage secondary to stroke and head trauma. A systematic search of randomised controlled trials, published between January 1, 2013 and June 30, 2017 in English and Spanish, was carried out in the PubMed, Cochrane plus Library and Ovid databases. We finally selected 17 studies, with methodological quality that was at least acceptable according to the Jadad scale. The most frequently investigated treatments are botulinum toxin, especially serotype A, together with rehabilitative measures. Clinical scales are the most frequently used to assess spasticity.

Background Chronic Urticaria (CU) is a debilitating disease whose treatment is mainly symptomatic. UCREX study aimed to identify CU patients’ profile, disease management and quality-of-life (QoL) in daily clinical practice in Spain. Methods Observational, 12-months prospective, multicenter study, included de novo or established CU patients attending to dermatology/allergy consultations in 39 Spanish hospitals. Main variables: Urticaria Activity Score (UAS), UAS over 7 days (UAS7). Secondary variables: CU-QoL Questionnaire (CU-Q2oL), EuroQol-5 dimensions (EQ-5D), Medical Outcomes Study Sleep (MOS-Sleep) scale, Hospital Anxiety and Depression Scale (HADS). Results 361 patients included. Of them, 176 (48.8%) considered for the main objective analysis. Mean age (SD) of 46.6 (14.2) years and 71.8% women. The year prior to inclusion, most patients (57.1%) were treated with non-sedating H1-antihistamines (NS-H1AH). At baseline, mean (SD) 3.6 (6.8) visits were registered to primary care. Mean (SD) UAS7 at baseline was 14.3 (11.0) and CU-Q2oL 24.1 (17.0) which tended to improve by 8.6 (9.7) and 13.9 (15.0), respectively, at 12-months. MOS-Sleep and EQ-5D remained steady during the study, except pain/discomfort and anxiety/depression which went from 58.7% and 49.6% to 29.6% and 26.9%, respectively. At baseline, HADS showed a mean (SD) anxiety of 8.7 (4.5) and depression 5.1 (4.4), decreasing to 7.0 (4.3) and 4.7 (4.3), respectively, at 12-months. Conclusions Although most CU patients are treated with NS-H1AH, disease activity is still important, negatively affecting patients’ QoL, work activity and healthcare resources use. An appropriate disease management could be the basis for symptoms control, QoL improvement and resources optimization.

Resumen La movilización del ángulo esplénico del colon es considerada una maniobra compleja y de las más desafiantes en la cirugía colorrectal con vía laparoscópica. A pesar de que existen distintas opciones quirúrgicas para llevarla a cabo, el abordaje de medial a lateral debe ser la técnica de elección. A continuación, se presenta la técnica quirúrgica y la ventajas de este abordaje.

Introduction Benefit from adjuvant chemotherapy (CT) is doubtful in a high percentage of patients with early breast cancer. The 21-gene recurrence-score (RS) assay (Oncotype DX, Genomic Health) is one gene-expression assay that provide prognostic and predictive information in hormone-receptor (RH) positive breast cancer. The results of the TAILORx study have confirmed that the majority of patients with tumors RH + and HER2 negative can avoid CT without increasing their risk of relapse. From 2012 to 2015 we used Mammaprint (MMP), in our institution and 60% of cases could avoided CT (communicated in SABCS 2015). Since 2017 we use RS for this purpose. Primary Objective To analyze the impact of using RS to change the indication of adjuvant CT. Secondary Objectives To analyze the association between different clinical pathological factors and the RS value, and calculate the difference between the cost of all RS test and the cost in direct expense of the treatment with CT of all patients who could avoid it thanks to the RS Material and methods We analyzed all RS test performed in the three ICO centers during 2017. We sent 112 tumor samples; in 2 samples adequated RNA for RS was not obtained. We compared the adjuvant treatment initially planned according to institutional treatment protocol with the treatment given after RS. We compared the direct economic costs of CT with the costs of the diagnostic test, and performed a logistic regression analysis of some pathological factors and RS value. Results The RS could be determined in 110 of 112 cases, in which there was indication of adjuvant CT. Only 14 patients received CT (12,72%) with the RS value, so CT was avoided in 96 patients (87,28%). The clinical-pathological characteristics of the series are summarized in the table 1. Of the risk factors analyzed, only grade 3 (p 0.001) and PR 25. No association was found between age, nodal status, tumor diameter, Ki67, Infiltrating Ductal Carcinoma vs neither Infiltrating Lobular Carcinoma nor Lympho-Vascular invasion. The cost of the genetic studies was 180000€ (1636€ each). The cost of each CT schedule (EC x 4 followed by paclitaxel x 12) was 7214€ and the total cost of 96 cases 692590€. Direct costs savings estimated from the reduction in CT treatment were 512590€ Conclusion: Our series shows that RS avoided unnecessary CT in 87% of cases and was more cost-effective than a previous series with MMP. G3 and RP 25. Table 1.Patients characteristics and clinical-pathological details from the analyzed tumorsPatient characteristicsAge, mean (range)53,76 (19 – 75)≥50y72 (65.5%) Citation Format: Ferrer M, Dorcas J, Quiroga V, Margelí M, del Barco S, Stradella A, Petit A, Falo C, Viñas G, Romeo M, Villanueva R, Cirauqui B, Vázquez S, Fernández A, Recalde S, Vethencourt A, Soler T, Pérez-Martín X, Gil-Gil M. Impact of oncotype dx genetic signature used in early breast cancer. Clinical and economic analisys of a 110 patient cohort treated in the Catalan Oncologic Institute (ICO), Spain [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-15-09.

Introduction Breast cancer is one of the most prevalent cancers in the world. Traditionally, early breast cancer treatment is based on surgery and, after surgery, hormone treatment or chemotherapy. However, the neoadjuvant treatment is increasingly used. Metabolomics is the most recent “omics” which allows quantify metabolites into blood patient samples. Coupled with computational analyses it could be possible to study differential metabolomics patterns and associate them with neoadjuvant response. Material and methods Blood plasma samples from patients with breast cancer treated with neoadjuvant chemotherapy were used to perform metabolomics experiments. One sample before the treatment (basal) and one sample after the chemotherapy (post-treatment) were analyzed and clinical data regarding response (complete response or partial response) was also collected. Metabolomics experiments were performed using liquid chromatography coupled with mass-spectrometry. Bayesian network and class comparison analyses were used to establish differential metabolic patterns between conditions. Additionally, a response prediction model based on logistic regression was build using metabolomics data from basal samples. Results and discussion A network showing the relationships between metabolites was build. Comparing metabolite measurements between complete response and partial response tumors in basal samples, 19 metabolites showed a differential quantification between both types of responses. Moreover, one of these metabolites is linoleic acid, previously described as a biomarker of complete response in neoadjuvant treatment in breast cancer. Using these 19 differential metabolites, a response predictive model was build. According to this model, it is possible to predict response to neoadjuvant treatment based on the amount of one metabolite, still only identified by its mass and charge. On the other hand, comparing basal and post-treatment samples, the network showed differential metabolomics patterns. These differential metabolites could be used as predictive biomarkers of response. Conclusion This study is a proof of concept that using a new “omics” technique such as metabolomics in blood samples, coupled with computational analyses, it is possible to identify differential metabolomics patterns between complete and partial response or basal and post-treatment samples and design predictive models of response These results could facilitate in the future the implementation of blood-based tests into the clinical routine. Citation Format: Zamora P, Trilla-Fuertes L, Zapater-Moros A, Gámez-Pozo A, Prado-Vázquez G, Ferrer-Gómez M, Díaz- Almirón M, López Vacas R, Espinosa E, Fresno Vara JA. A pilot study of metabolomics biomarkers in breast cancer tumors treated with neoadjuvant therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-12-14.

In recent years the immunomodulatory actions of vitamin D, a steroid hormone, have been extensively studied. In 2020, due to the COVID-19 pandemic, the question arose as to 25(OH)D status would be related to susceptibility to SARS-CoV-2 infection, since several studies pointed out a higher prevalence and severity of the disease in populations with low levels of 25(OH)D. Thus, we investigated the 25(OH)D levels in adults “Detected” positive for SARS CoV-2 by RT-PCR (reverse transcriptase polymerase chain reaction) test, and in negative controls, “not Detected”, using the Fleury Group's examination database, in Sao Paulo, Brazil. Of a total of 14.692 people with recent assessments of 25(OH)D and RT-PCR tests for COVID-19, 2.345 were positive and 11.585 were negative for the infection. The groups did not differ in the percentage of men and women, or in the age distribution. There were no differences in the distribution of 25(OH)D between the two groups (p = 0.08); mean 25(OH)D of 28.8 ± 21.4 ng/mL and 29.6 ± 18.1 ng/mL, respectively. In the specific population studied, clinical, environmental, socioeconomic and cultural factors should have greater relevance than 25(OH)D in determining the susceptibility to COVID-19.

Graphical abstract, Highlights • Detection of cytokine storm biomarkers with mobile biosensors. • Immunosensors are made solely of cellulose modified with antibody-decorated nanoparticles. • Turnaround time under 10 min. • Detection of biomarkers in respiratory samples allows monitoring local inflammation. • Compatible with decentralized health care schemes., Decentralizing COVID-19 care reduces contagions and affords a better use of hospital resources. We introduce biosensors aimed at detecting severe cases of COVID-19 in decentralized healthcare settings. They consist of a paper immunosensor interfaced with a smartphone. The immunosensors have been designed to generate intense colorimetric signals when the sample contains ultralow concentrations of IL-6, which has been proposed as a prognosis biomarker of COVID-19. This is achieved by combining a paper-based signal amplification mechanism with polymer-filled reservoirs for dispensing antibody-decorated nanoparticles and a bespoken app for color quantification. With this design we achieved a low limit of detection (LOD) of 10−3 pg mL-1 and semi-quantitative measurements in a wide dynamic range between 10−3 and 102 pg mL-1 in PBS. The assay time is under 10 min. The low LOD allowed us to dilute blood samples and detect IL-6 with an LOD of 1.3 pg mL-1 and a dynamic range up to 102 pg mL-1. Following this protocol, we were able to stratify COVID-19 patients according to different blood levels of IL-6. We also report on the detection of IL-6 in respiratory samples (bronchial aspirate, BAS) from COVID-19 patients. The test could be easily adapted to detect other cytokines such as TNF-α and IL-8 by changing the antibodies decorating the nanoparticles accordingly. The ability of detecting cytokines in blood and respiratory samples paves the way for monitoring local inflammation in the lungs as well as systemic inflammation levels in the body.

Sapovirus is a common cause of acute gastroenteritis in all age groups. Sapovirus infections are seldom investigated in Spain, and its epidemiology in the country is not well known. The use of molecular diagnostic procedures has allowed a more frequent detection of sapoviruses in patients with diarrhea. A total of 2545 stool samples from patients with acute gastroenteritis attended from June 2018 to February 2020 at the Clinic University Hospital in Valencia, Spain, were analyzed by reverse transcription (RT) and real-time multiplex PCR (RT-PCR) to investigate the etiology of enteric infections. Sapovirus was the second enteric virus detected with a positive rate of 8%, behind norovirus (12.2%) and ahead of rotavirus (7.1%), astrovirus (4.9%) and enteric adenoviruses (2.9%). Most sapovirus infections occurred in infants and young children under 3 years of age (74%) with the highest prevalence in autumn and early winter. Coinfections were found in 25% of the patients with sapovirus diarrhea, mainly with other enteric viruses. Genotyping demonstrated the circulation of seven different genotypes during the study period, with a predominance of genotypes GI.1, GI.2, and GII.1. Phylogenetic analysis showed that genogroup GII strains form a cluster separated from genogroup GI and GV, being genotype GV.1 strains related to genotype GI.1 and GI.2 strains.

The full impact of the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), on the field of hematopoietic cell transplantation (HCT) is unknown. This perspective paper reviews the following: current COVID-19 epidemiology, diagnosis, and potential therapies; care considerations unique to HCT recipients; and the concept of a learning network to assimilate emerging guidelines and best practices and to optimize patient outcomes through facilitating shared learning and experience across transplantation centers.

Background and objectives: To compare the medium- to long-term mechanical behavior of overdentures with two different retention systems: overdentures with Locator&reg, axial retention, and vertical insertion overdentures with bar retention, used to rehabilitate edentulous maxillar. Material and Methods: This prospective study assessed patients presenting complete maxillary edentulism, rehabilitated by means of implant-supported overdentures (n = 20), 10 with Locator&reg, axial retention (ODA group) and 10 with overdentures on bars (ODB group). Patients also completed a questionnaire to determine their satisfaction with treatment. Results: The mean follow-up time in both groups was 11.4 years, with follow-up times in both groups ranging from 5 to 14 years. The ODA group suffered mechanical complications such as retention loss, need for nylon retention insert changes, resin fracture, and need for relining. In the ODB group, prosthetic dental wear, screw loosening, and complete prosthetic failure were more common. A total of 19 implants failed (23.8%), of these, 11 were in the ODA group (failure rate = 27.5%) and eight in the ODB group (failure rate = 20%). The patient satisfaction questionnaire obtained a mean score of 7.9 out of 10 in the ODA group, and 9.75 in the ODB group. Conclusions: in rehabilitations of edentulous maxillar by means of implant-supported overdentures, both the systems assessed were shown to be effective in the medium to long term. Patients expressed a high level of satisfaction with the treatments received.

Humanitarian organizations transport large quantities of aid for distribution in the aftermath of disasters. Transportation for last mile distribution includes multiple, and often conflicting, performance criteria that include time (deprivation), cost, coverage, equity and security. We build a compromise programming model for multi-criteria optimization in humanitarian last mile distribution. Regarding security, ours is the first multi-criteria model able to produce an actual vehicle schedule while forcing vehicles to form convoys in humanitarian operations research. We illustrate the multi-criteria optimization using a realistic test case based on the Pakistan floods, 2010. We standardize and share this case as well as cases based on the Niger famine, 2005 and the Haiti earthquake, 2010. By sharing test cases, we encourage basic scientific tasks such as replicability and model comparison within the humanitarian operations research community.

Made available in DSpace on 2020-12-10T17:01:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-12-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Generalitat Valencia The density functional theory has become increasingly common as a methodology to explain the properties of crystalline materials because of the improvement in computational infrastructure and software development to perform such computational simulations. Although several studies have shown that the characteristics of certain classes of materials can be represented with great precision, it is still necessary to improve the methods and strategies in order to achieve more realistic computational modeling. In the present work, strategies are reported in a systematic way for the accurate representation of crystalline systems. The crystalline compound chosen for the study as a case test was BaMoO4, both because of its potential technological application and because of the low accuracy of the simulations previously reported in the literature. The computational models were carried out with the B3LYP and WC1LYP functionals selected from an initial set containing eight hybrid functionals in conjunction with an all-electron basis set. Two different strategies were applied for improving the description of the initial models, both involving atomic basis set optimization and Hartree-Fock exchange percentage adjustment. The results obtained with the two strategies show a precision of structural parameters, band gap energy, and vibrational properties never before presented in theoretical studies of BaMoO4. Finally, a flowchart of good calculation practices is elaborated. This can be of great value for the organization and conduction of calculations in new research. Univ Fed Rio Grande do Norte, LSQM Lab Chem Synth Mat, Natal, RN, Brazil Sao Paulo State Univ, Modeling & Mol Simulat Grp CDMF, BR-17033360 Bauru, SP, Brazil Univ Fed Pelotas, Dept Phys, BR-96010610 Pelotas, RS, Brazil UJI, Dept Analyt & Phys Chem, Castellon de La Plana 12071, Spain Univ Fed Sao Carlos, Chem Dept CDMF, POB 14801-907, Sao Carlos, SP, Brazil Sao Paulo State Univ, Modeling & Mol Simulat Grp CDMF, BR-17033360 Bauru, SP, Brazil CNPq: 432242/2018-0 CAPES: 787027/2013 CAPES: 8881.068492/2014-01 FAPESP: 2013/07296-2 FAPESP: 2016/07476-9 Generalitat Valencia: 2018/064

Aims Information on the impact of insulin therapy before pancreas donation on pancreas outcomes is scarce. We aim to explore the influence of insulin therapy before donation on recipient and pancreas graft survival. Methods Registry study including 12,841 pancreas recipients from the OPTN/UNOS registry performed between 2000 and 2017. Inverse probability of treatment weighting (IPTW) was used to account for covariate imbalance between recipients from a donor with and without insulin requirements. Results A total of 7765 (60%) patients received a pancreas from a donor with insulin before donation (IBD). Pancreas graft survival (death-censored) was similar between recipients from IBD and non-IBD donors at 1, 5 and 10 years (89% vs 89%, 78% vs 79 and 69% vs 70%, respectively, P = 0.35). Recipients from IBD donors presented a similar 90-days pancreas graft survival. After IPTW weighting, IBD donors were neither associated with any post-transplant surgical complication (HR 1.11 [95% CI 0.98–1.24], P = 0.06), nor with risk for recipient death (HR 0.94 [95% CI 0.85–1.04], P = 0.26), nor pancreas graft failure (HR 1.06 [95% CI 0.98–1.16], P = 0.15). Conclusions Insulin therapy before donation in accepted pancreas donors was not associated, per se, with an impaired pancreas graft and patient survival.

Background:The antisynthetase syndrome (SAS) is characterized by the presence of antisynthetase antibodies, anti-JO1, PL7 y PL12 are the most common; and the classic triad of myositis, arthritis, and diffuse interstitial lung disease (ILD)1. Most patients present incomplete forms and the severity of the ILD determines the prognosis of the disease2.Objectives:to analyze epidemiological, clinical and serological characteristics and treatments used in a cohort of patients with SAS.Methods:descriptive study of review of medical records. Data were collected from 15 patients with SAS followed in the Rheumatology and Pneumology consultations of the Virgen Macarena Hospital (Seville) in the last 10 years. The analysis was carried out using the R software.Results:15 patients were included, 8 men and 7 women. The median age was 56 years (33-77). Seven patients (47%) used to smoke. Four patients (27%) met the classical triad. All of them presented ILD and 8 patients (53%) had arthritis and / or myositis. Five (33%) had mechanic’s hands and six of them (40%) presented Raynaud. Seven (47%) suffered from dyspnea before the SAS diagnosis. The median diagnostic delay was 1 month (0-43). Seven (47%) patients had anti-JO1, 1 (7%) anti-PL7, 2 (13%) anti-PL12 and 2 (13%) patients anti-Ro52. Radiological patterns detected by HRCT were: 5 (33%) NINE, 4 (37%) NIU and 6 (40%) others. The initial treatment included mostly (66%) glucocorticoids (GC) and one or more cFAME. In maintenance, mycophenolate was used in 7 patients (47%), cyclosporine 5 (33%), cyclophosphamide in 3 cases (20%), azathioprine in 3 patients (20%) and methotrexate in 3 of them (20%). Four (37%) patients required a combination of DMARDs and 2 cases needed (13%) biological therapy, Rituximab and Tocilizumab. Changes in the mean value of the initial respiratory function tests (FVC1 and DLCO1) and during follow-up (FVC2 and DLCO2) were not relevant (FVC1 81.5% [42-110], FVC2 81% [59-115]; DLCO1 83% [10-112], DLCO2 80.5% [47-108]). Nine patients (60%) remained clinically stable and 3 patients (20%) progressed radiologically. Four patients died from ILD progression.Conclusion:In this study, the incomplete diagnosis of SAS predominated. The most detected antibody was anti-JO1. ILD is present in all cases, with NINE being the most frequent pattern so multidisciplinary management is necessary. Most used treatments were GC and FAMES combined, some cases required biological therapy.References:[1]Irazoque F, et al. Epidemiology, etiology and classification. Reumatol Clin. 2009;5:2-5.[2]Johnson C, et al. Clinical and pathologic differences in interstitial lung disease based on antisynthetase antibody type. Respir Med. 2014; 108(10):1542-8.Disclosure of Interests:None declared

Lima bean (Phaseolus lunatus L.) is an important crop in the Mayan culture. The Mayan area, considered as a main center of Mesoamerican diversity, has been divided into two subareas: the Mayan lowlands and the Mayan highlands. The Yucatan Peninsula is part of the Mayan lowlands and holds the highest number of Lima bean landraces of Mexico, but Lima beans are in high risk of genetic erosion due to intensification of the traditional Mayan agriculture. However, information on genetic diversity of Lima beans of the Mayan highlands is lacking. By using 46 landraces collected in the Mayan area (23 from each subarea) and 73 ISSR loci (inter-simple sequence repeats), we analyzed the structure, diversity and genetic relationships of Lima beans of this part of Mesoamerica. High levels of diversity (H BAY = 0.45) and genetic structure (F ST = 0.66) were found for the whole Mayan area. Genetic diversity in the Mayan lowlands was apparently higher than the Mayan highlands (H BAY = 0.44 and 0.36, respectively); but differences were not statistically significant. Genetic structure between the subareas was high (AMOVA = 30% of total variation), most landraces grouping according to their geographic origin. This study shows the importance of the Mayan culture in the diversification and conservation of Lima beans. The results provide important information that should be considered when implementing strategies to collect Lima bean landraces and planning in situ and ex situ programs to conserve these landraces in the Mayan region.

From 2002 to 2011, there were more than 17,000 shootings in Philadelphia. "Turning Point," Temple University Hospital's inpatient violence intervention program, takes advantage of the teachable moment that occurs after violent injury. In addition to receiving traditional social work services, Turning Point patients watch their trauma bay resuscitation video and a movie about violence, meet with a gunshot wound survivor and an outpatient case manager, and also undergo psychiatric assessment. The purpose of this study was to determine the efficacy of Turning Point in changing attitudes toward guns and violence among victims of penetrating trauma.This prospective randomized study was conducted from January 2012 to January 2014. Patients who sustained a gunshot or stab wound were randomized to standard of care, which involved traditional social work services only, or Turning Point. The Attitudes Toward Guns and Violence Questionnaire was administered to assess attitude change. Analysis was performed with repeated-measures analysis of variance. A p0.05 was significant.A total of 80 of a potential 829 patients completed the study (40 standard of care, 40 Turning Point). The most common reason for exclusion was anticipated length of stay being less than 48 hours. The two groups were similar with respect to most demographics. Unlike the standard-of-care group, the Turning Point group demonstrated a 50% reduction in aggressive response to shame, a 29% reduction in comfort with aggression, and a 19% reduction in overall proclivity toward violence.Turning Point is effective in changing attitudes toward guns and violence among victims of penetrating trauma. Longer follow-up is necessary to determine if this program can truly be a turning point in patients' lives.Therapeutic/care management study, level II.

Background Calcific aortic valve disease is the 2nd most frequent cause of open heart surgery. The valve interstitial cells (VIC) are crucial for calcification. SNF472 (a derivative of phytic acid) is a calcification inhibitor currently in clinical development for the treatment of cardiovascular calcification (Phase 2 CaLIPSO trial, EudraCT 2016–002834–59). SNF472 has been shown to inhibit vascular calcification in several preclinical models. Purpose 1. Establish a new model of calcification in cultured human VIC; 2. Investigate whether SNF472 would inhibit calcification in this model, and 3. Study if SNF472 might inhibit ongoing calcification processes. Methods Healthy and calcified aortic valves were obtained from heart transplant recipients and patients undergoing aortic valve replacement due to calcific valve disease, respectively. VIC were isolated and seeded in basic growth medium, osteogenic differentiation medium (Osteodiff) alone, and with addition of different concentrations of SNF472. The following series of studies were performed: 1. VIC from healthy and calcified valves were cultured for three weeks with Osteodiff; 2. VIC from calcified valves were cultured for 3 weeks in Osteodiff media with 0, 1, 3, 10, 30, or 100 μM SNF472; 3. VIC from calcified valves were cultured for 3 weeks in Osteodiff media in total, but after 1 or 2 weeks 30 or 100 μM SNF472 was added to the cultures (n=8). Calcification was visualized by Alzarin Red staining and quantified by spectrophotometry. Statistics analysis was performed nonparametric One-Way ANOVA (Friedman and Kruskal–Wallis tests) with Dunn's post-test. Results Calcification was found to be 30% stronger in cultures of VIC from calcified valves as compared to cultured VIC from healthy valves (p=0.03). SNF472 successfully inhibited VIC calcification in a dose-dependent manner. SNF472 concentrations of 1, and 3 μM inhibited calcification by 7% (not significant) and 66% (p=0.08) respectively. Concentrations of 10, 30, and 100 μM completely inhibited calcification. 30 and 100 μM of SNF472 added after 1 week reduced ongoing calcification by 84% (p Conclusions VIC from calcified valves have a more pro-calcification phenotype than VIC from healthy valves. SNF472 is able to inhibit the development VIC calcification in vitro. By early intervention SNF472 is also able to stop the progression of ongoing calcification. SNF472 shows to be a promising therapy to treat heart valve calcification. Acknowledgement/Funding EC FP7 (GA 609020), Balearic Islands Government grant (ES01/TCAI/41_2017), FEDER 2014-2020, Laboratoris Sanifit, Palma, Spain; University of Oslo

Aims The Acute Cardiac Care Association (ACCA)–European Association of Percutaneous Coronary Intervention (EAPCI) Registry on ST-elevation myocardial infarction (STEMI) of the EurObservational programme (EORP) of the European Society of Cardiology (ESC) registry aimed to determine the current state of the use of reperfusion therapy in ESC member and ESC affiliated countries and the adherence to ESC STEMI guidelines in patients with STEMI. Methods and results Between 1 January 2015 and 31 March 2018, a total of 11 462 patients admitted with an initial diagnosis of STEMI according to the 2012 ESC STEMI guidelines were enrolled. Individual patient data were collected across 196 centres and 29 countries. Among the centres, there were 136 percutaneous coronary intervention centres and 91 with cardiac surgery on-site. The majority of centres (129/196) were part of a STEMI network. The main objective of this study was to describe the demographic, clinical, and angiographic characteristics of patients with STEMI. Other objectives include to assess management patterns and in particular the current use of reperfusion therapies and to evaluate how recommendations of most recent STEMI European guidelines regarding reperfusion therapies and adjunctive pharmacological and non-pharmacological treatments are adopted in clinical practice and how their application can impact on patients’ outcomes. Patients will be followed for 1 year after admission. Conclusion The ESC ACCA-EAPCI EORP ACS STEMI registry is an international registry of care and outcomes of patients hospitalized with STEMI. It will provide insights into the contemporary patient profile, management patterns, and 1-year outcome of patients with STEMI.

Background: Colorectal cancer (CRC) is the second cause of tumour mortality in Spain and Europe. To date, no studies have been conducted in Spain to evaluate the spatial and temporal distribution of the excess risk of death during hospitalisation for CRC. Methods: A cohort was constructed of all episodes of hospitalisation in Spain due to CRC (codes 153 and 154 of the International Classification of Diseases, 9th edition, Clinical Modification) during the period 2008-2014, based on the minimum basic data set published by the Ministry of Health. Mortality ratios were calculated per region for each of the years analyzed (spatial or cross-sectional analysis) and during the overall study period, for each region independently (temporal or longitudinal analysis). In the first of these analyses, particular note was taken of the regions and years in which the limits of two and three standard deviations were exceeded. Results: Two hundred and fifty eight thousand, nine hundred and twenty seven episodes of CRC were analysed. The patients were predominantly male (60.6%), with an average hospital stay of 13.16 days. Half underwent surgery during admission and on average presented more than six diagnoses at discharge. The spatial analysis revealed mortality ratios that deviated by at least three standard deviations in the following regions: Islas Canarias, Asturias, Valencia, Extremadura, País Vasco and Andalucía. The longitudinal analysis showed that most regions presented one or more years when CRC mortality was at least 15% higher than expected during the period; outstanding in this respect were Asturias, Navarra and La Rioja, where this excess risk was detected in at least 2 years. Conclusions: Geographic and temporal patterns of the distribution of the excess risk of mortality from CRC in Spain are described using SMRs. We conclude that during the study period, the geographic pattern of mortality in Spain did not coincide with the excess risk of mortality calculated using the SMR method described by Jarman and Foster. This method of risk estimation can be a useful tool for the study of mortality risk and its spatial variations. Yes

Triple-negative breast cancer is a heterogeneous disease characterized by a lack of hormonal receptors and HER2 overexpression. It is the only breast cancer subgroup that does not benefit from targeted therapies, and its prognosis is poor. Several studies have developed specific molecular classifications for triple-negative breast cancer. However, these molecular subtypes have had little impact in the clinical setting. Gene expression data and clinical information from 494 triple-negative breast tumors were obtained from public databases. First, a probabilistic graphical model approach to associate gene expression profiles was performed. Then, sparse k-means was used to establish a new molecular classification. Results were then verified in a second database including 153 triple-negative breast tumors treated with neoadjuvant chemotherapy. Clinical and gene expression data from 494 triple-negative breast tumors were analyzed. Tumors in the dataset were divided into four subgroups (luminal-androgen receptor expressing, basal, claudin-low and claudin-high), using the cancer stem cell hypothesis as reference. These four subgroups were defined and characterized through hierarchical clustering and probabilistic graphical models and compared with previously defined classifications. In addition, two subgroups related to immune activity were defined. This immune activity showed prognostic value in the whole cohort and in the luminal subgroup. The claudin-high subgroup showed poor response to neoadjuvant chemotherapy. Through a novel analytical approach we proved that there are at least two independent sources of biological information: cellular and immune. Thus, we developed two different and overlapping triple-negative breast cancer classifications and showed that the luminal immune-positive subgroup had better prognoses than the luminal immune-negative. Finally, this work paves the way for using the defined classifications as predictive features in the neoadjuvant scenario.

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Background and objectives: Percentages of blood CD19 + CD5 + B cells and CD8 + perforin + T lymphocytes can predict response to Interferon (IFN)-beta treatment in relapsing-remitting multiple sclerosis (RRMS) patients. We aimed to standardize their detection in a multicenter study, prior to their implementation in clinical practice. Methods: Fourteen hospitals participated in the study. A reference centre was established for comparison studies. Peripheral blood cells of 105 untreated RRMS patients were studied. Every sample was analyzed in duplicate in the participating centre and in the reference one by flow cytometry. When needed, participating centres corrected fluorescence compensations and negative cut-off position following reference centre suggestions. Concordance between results obtained by participating centres and by reference one was evaluated by intraclass correlation coefficients (ICC) and Spearman correlation test. Centre performance was measured by using z-scores values. Results: After results review and corrective actions implementation, overall ICC was 0.86 (CI: 0.81-0.91) for CD19 + CD5 + B cell and 0.89 (CI: 0.85-0.93) for CD8 + perforin + T cell quantification; Spearman r was 0.92 (0.89-0.95; p < 0.0001) and 0.92 (0.88-0.95; p < 0.0001) respectively. All centres obtained z-scores 5 0.5 for both biomarkers. Conclusion: Homogenous percentages of CD19 + CD5 + B cells and CD8 perforin + T lymphocytes can be obtained if suitable compensation values and negative cut-off are pre-established.

BackgroundMuscle-invasive bladder tumors are associated with high risk of relapse and metastasis even after neoadjuvant chemotherapy and radical cystectomy. Therefore, further therapeutic options are needed and molecular characterization of the disease may help to identify new targets.ObjectiveThe aim of this work is to characterize muscle-invasive bladder tumors at molecular levels using computational analyses.Design, Settings and ParticipantsThe TCGA cohort of muscle-invasive bladder cancer patients was used to describe these tumors.Outcome Measurements and Statistical AnalysisProbabilistic graphical models, layer analyses based on sparse k-means coupled with Consensus Cluster, and Flux Balance Analysis were applied to characterize muscle-invasive bladder tumors at functional level.ResultsLuminal and Basal groups were identified, and an immune molecular layer with independent value was also described. Luminal tumors had decreased activity in the nodes of epidermis development and extracellular matrix, and increased activity in the node of steroid metabolism leading to a higher expression of androgen receptor.This fact points to androgen receptor as a therapeutic target in this group. Basal tumors were highly proliferative according to Flux Balance Analysis, which make these tumors good candidates for neoadjuvant chemotherapy. Immune-high group had higher expression of immune biomarkers, suggesting that this group may benefit from immune therapy.ConclusionsOur approach, based on layer analyses, established a Luminal group candidate for androgen receptor inhibitor therapy, a proliferative Basal group which seems to be a good candidate for chemotherapy, and an immune-high group candidate for immunotherapy.Patient SummaryMuscle-invasive bladder cancer has a poor prognosis in spite of appropriate therapy. Therefore, it is still necessary to characterize these tumors to propose new therapeutic targets. In this work we used computational analyses to characterize these tumors and propose treatments.

Chronic spontaneous urticaria (CSU) is a heterogeneous condition that can severely impact quality of life. Consequently, rapid disease control is essential. First-line treatment of the symptoms of CSU is the licensed dose of second-generation H1 antihistamines. For second-line treatment, this dose may be increased by up to 4 times. In patients who fail to respond to higher doses of H1 antihistamines, omalizumab for up to 24 weeks is recommended to achieve disease control. After this 24-week period, the patient's response to omalizumab should be assessed in order to identify refractory patients. Optimal management of refractory patients has not been established. Therefore, the aim of the present consensus document, which was drafted by allergists and dermatologists with specific expertise in treating urticaria, was to define specific patient profiles based on differences in their response to omalizumab. We also developed a treatment algorithm based on the specific response profile. After a comprehensive literature review, a group meeting was held to discuss issues related to the therapeutic management of patients with CSU that had not been addressed in previous studies. The experts considered both the available evidence and their own clinical experience with omalizumab. We believe that implementation of the proposed algorithm will optimize management of CSU patients who are refractory to antihistamines, reduce disease-related costs, and improve quality of life.

Large scale disasters, natural or human-made, have huge consequences on people and infrastructures. After a disaster strikes, the distribution of humanitarian aid to the population affected is one of the main operations to be carried out, and several crucial decisions must be made in a short time. This paper addresses a last-mile distribution problem in disaster relief operations, under insecure and uncertain conditions. A model is presented that takes into account the cost and time of operation, the security and reliability of the routes, and the equity of aid handed out. The output of the model consists of a detailed set of itineraries that can be used to build an implementable distribution plan. Given its high complexity, the resulting problem is solved using a multi-criteria metaheuristic approach. In particular, a constructive algorithm and a GRASP based metaheuristic are developed, which are tested in a case study based on the 2010 Haiti earthquake.

Mutational analysis of RAS is required for anti-epidermal growth factor receptor (EGFR) treatment for patients with metastatic colorectal cancer (mCRC). However, most patients with KRAS wild-type tumors still do not respond. Other molecules downstream of the EGFR may also play a role in resistance to EGFR therapies. Our objective was to investigate the clinical importance of biomarkers in relation to response, progression-free survival, and overall survival in patients with mCRC receiving first-line treatment with anti-EGFR therapy plus chemotherapy. We studied the EGFR pathway [EGFR, NRAS, BRAF, PIK3CA, phosphatase and tensin homolog (PTEN), amphiregulin (AREG), and epiregulin (EREG)] in 105 patients with mCRC KRAS codon 12 wild type. We analysed objective response, progression-free survival, and overall survival in molecularly defined subgroups of the patients receiving anti-EGFR therapy plus chemotherapy as first-line treatment. We found a significant association between RAS wild-type, BRAF wild-type, EREG, and AREG overexpression and response to anti-EGFR therapy (p = 0.003, p = 0.015, p = 0.05, and p = 0.009, respectively). Progression-free survival and overall survival were lower in patients with RAS (p = 0.36 and p ≤ 0.001, respectively) or BRAF (p = 0.003 and p = 0.002, respectively) mutant tumors. Patients with EREG and AREG messenger RNA (mRNA) expression had longer survival than those with low-expression tumors; progression-free survival and overall survival were significant for AREG (p = 0.001 and p = 0.05, respectively). Patients with EGFR amplification tumors responded better to treatment and had better survival rates, although this was not significant. PIK3CA and PTEN were not associated with either response or survival. The multivariate logistic regression model for response showed only BRAF as a significant predictor after adjustment for the other covariates (p = 0.04, odds ratio 8.3, 95 % confidence interval 0.81–86.0). RAS, BRAF, AREG, and EREG predict for efficacy of first-line anti-EGFR therapy in patients with mCRC.

Deficient angiogenesis may contribute to worsen the prognosis of myocardial ischemia, peripheral arterial disease, ischemic stroke, etc. Dyslipidemic and inflammatory environments attenuate endothelial cell (EC) proliferation and angiogenesis, worsening the prognosis of ischemia. Under these dyslipidemic and inflammatory environments, EC-caspase-1 becomes activated and induces inflammatory cell death that is defined as pyroptosis. However, the underlying mechanism that correlates caspase-1 activation with angiogenic impairment and the prognosis of ischemia remains poorly defined. By using flow cytometric analysis, enzyme and receptor inhibitors, and hind limb ischemia model in caspase-1 knock-out (KO) mice, we examined our novel hypothesis, i.e. inhibition of caspase-1 in ECs under dyslipidemic and inflammatory environments attenuates EC pyroptosis, improves EC survival mediated by vascular endothelial growth factor receptor 2 (VEGFR-2), angiogenesis, and the prognosis of ischemia. We have made the following findings. Proatherogenic lipids induce higher caspase-1 activation in larger sizes of human aortic endothelial cells (HAECs) than in smaller sizes of HAECs. Proatherogenic lipids increase pyroptosis significantly more in smaller sizes of HAECs than in larger sizes of the cells. VEGFR-2 inhibition increases caspase-1 activation in HAECs induced by lysophosphatidylcholine treatment. Caspase-1 activation inhibits VEGFR-2 expression. Caspase-1 inhibition improves the tube formation of lysophosphatidylcholine-treated HAECs. Finally, caspase-1 depletion improves angiogenesis and blood flow in mouse hind limb ischemic tissues. Our results have demonstrated for the first time that inhibition of proatherogenic caspase-1 activation in ECs improves angiogenesis and the prognosis of ischemia.

Resumen: La osteopetrosis (OP) es una rara enfermedad ósea congénita producida por una alteración funcional en los osteoclastos con incapacidad para la reabsorción ósea normal, produciéndose un aumento de la densidad mineral ósea y esclerosis ósea. Puede clasificarse en autosómica recesiva (OPTB) o autosómica dominante (OPTA1-2). Existe una gran variabilidad clínica de la enfermedad, desde asintomática a letal en los primeros meses de vida, con expresividad variable en los miembros de una familia. Su diagnóstico es principalmente clínico con confirmación genética, y el tratamiento es sintomático. Se presentan una serie de casos de OP, con el hallazgo de una nueva mutación en el gen LRP5 causante de OPTA1 en uno de ellos. Abstract: Osteopetrosis (OP) is a congenital bone disease which is caused by a functional disorder in osteoclasts with inability for normal bone resorption, leading to increased bone mineral density and bone sclerosis. It can be classified into different groups according to their clinical and their genetic characteristics: autosomal recessive with several subtypes (OPTB) or autosomal dominant type 1 or 2 (OPTA1-2). There is a wide clinical variability of the disease, from asymptomatic to lethal in the first months of life, with variable expressivity in the family members. Diagnosis is mainly clinical with genetic confirmation of the OP, and treatment is symptomatic. Three cases of OP are presented, with the discovery of a new gene mutation in LRP5 which caused OPTA1 in one of them.

Vascular access dysfunction associated with arteriovenous grafts and fistulas contributes to the morbidity and mortality of chronic kidney disease (CKD) patients receiving hemodialysis. We hypothesized that the uremic conditions associated with CKD promote a pathophysiological vascular smooth muscle cell (VSMC) phenotype that contributes to neointimal hyperplasia. We analyzed the effect of culturing human VSMC with uremic serum. Expression of VSMC contractile marker genes was reduced 50-80% in cells exposed to uremic serum and the decreased expression was accompanied by changes in histone marks. There was an increase in proliferation in cells exposed to uremic conditions, with no change in the levels of apoptosis. Interestingly, we found that uremic serum inhibited PDGF-induced migration of VSMC. Histomorphometric analysis revealed venous neointimal hyperplasia in veins from chronic kidney disease (CKD) patients prior to any surgical manipulation as compared to veins from patients with no kidney disease. We conclude that uremia associated with CKD alters VSMC phenotype in vitro and contributes to neointimal hyperplasia formation in vivo contributing to the pathogenesis of vascular access dysfunction in CKD patients.

The pathogenesis of life-threatening influenza A virus (IAV) disease remains elusive, as infection is benign in most individuals. We studied two relatives who died from influenza. We Sanger sequenced GATA2 and evaluated the mutation by gene transfer, measured serum cytokine levels, and analyzed circulating T- and B-cells. Both patients (father and son, P1 and P2) died in 2011 of H1N1pdm IAV infection at the ages of 54 and 31 years, respectively. They had not suffered from severe or moderately severe infections in the last 17 (P1) and 15 years (P2). A daughter of P1 had died at 20 years from infectious complications. Low B-cell, NK- cell, and monocyte numbers and myelodysplastic syndrome led to sequence GATA2. Patients were heterozygous for a novel, hypomorphic, R396L mutation leading to haplo-insufficiency. B- and T-cell rearrangement in peripheral blood from P1 during the influenza episode showed expansion of one major clone. No T-cell receptor excision circles were detected in P1 and P3 since they were 35 and 18 years, respectively. Both patients presented an exuberant, interferon (IFN)-γ-mediated hypercytokinemia during H1N1pdm infection. No data about patients with viremia was available. Two previously reported adult GATA2-deficient patients died from severe H1N1 IAV infection; GATA2 deficiency may predispose to life-threatening influenza in adulthood. However, a role of other genetic variants involved in immune responses cannot be ruled out. Patients with GATA2 deficiency can reach young adulthood without severe infections, including influenza, despite long-lasting complete B-cell and natural killer (NK) cell deficiency, as well as profoundly diminished T-cell thymic output.