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The neutrophil-to-lymphocyte ratio (NLR) in the diagnosis of sepsis has been found to be higher in non-survivors than in survivors, and that is associated with mortality. A higher NLR in non-survivors than in survivors has been reported in two studies during patient follow-up; however, NLR was not controlled for sepsis severity. Thus, the objective of this study was to determine whether there is an association between NLR in the first seven days and mortality controlling for sepsis severity.This observational study, which included septic patients, was conducted in the Intensive Care Units of 3 Spanish hospitals. NLR was recorded on the first, fourth, and eighth day of sepsis. Multiple logistic regression analyses were carried out to determine the association between NLR during the first 7 days of sepsis diagnosis and mortality controlling for sepsis severity.Thirty-day non-surviving patients (n=68) compared to surviving patients (n=135) showed higher NLR on the first (p0.001), fourth (p0.001), and eighth (p0.001) day of sepsis diagnosis. Multiple logistic regression analysis found an association between NLR at days first (p0.001), fourth (p=0.004), and eighth (p=0.01) of sepsis diagnosis and mortality controlling for SOFA and lactic acid in those days.The new finding of our study was the association between NLR in the first seven days of sepsis and mortality controlling for sepsis severity.

There are not data on blood B-cell lymphoma 2 (Bcl-2) concentrations (one of the antiapoptotic molecules of the Bcl-2 family in the intrinsic apoptosis pathway) in septic patients. Therefore, this study was carried with the aims to explore whether blood Bcl-2 concentrations at diagnosis of sepsis are different in survivor and non-survivor septic patients, are associated with mortality, and are useful for the mortality prediction.Intensive Care Units from 3 Spanish hospitals participated in this observational and prospective study with septic patients and serum Bcl-2 concentrations at diagnosis of sepsis were determined. Mortality at 30 days was as outcome variable.We found that 30-day non-surviving patients (n=81) showed lower serum Bcl-2 levels (p=0.003) than surviving patients (n=140). We found that serum concentrations of Bcl-24.4ng/mL were associated with mortality (OR=3.228; 95% CI=1.406-7.415; p=0.006) in the multiple logistic regression analysis, and that showed an area under the curve for mortality prediction of 62% (95% CI=55-68%; p=0.003).In our study appears novel findings such as higher blood Bcl-2 concentrations in survivor than in non-survivor septic patients, the association between low blood Bcl-2 concentrations and mortality of septic patients, and the ability of blood Bcl-2 concentrations for the prediction of septic patient mortality.

Objective Different genetic polymorphisms of human leukocyte antigen (HLA) have been associated with the risk and prognosis of autoimmune and infectious diseases. The objectives of this study were to determine whether there is an association between HLA genetic polymorphisms and the susceptibility to and mortality of coronavirus disease 2019 (COVID-19) patients. Design Observational and prospective study. Setting Eight Intensive Care Units (ICU) from 6 hospitals of Canary Islands (Spain). Patients COVID-19 patients admitted in ICU and healthy subjects. Interventions Determination of HLA genetic polymorphisms. Main variable of interest Mortality at 30 days. Results A total of 3886 healthy controls and 72 COVID-19 patients (10 non-survivors and 62 survivor patients at 30 days) were included. We found a trend to a higher rate of the alleles HLA-A*32 (p = 0.004) in healthy controls than in COVID-19 patients, and of the alleles HLA-B*39 (p = 0.02) and HLA-C*16 (p = 0.02) in COVID-19 patients than in healthy controls; however, all these p-values were not significant after correction for multiple comparisons. Logistic regression analysis showed that the presence of certain alleles was associated with higher mortality, such as the allele HLA-A*11 after controlling for SOFA (OR = 7.693; 95% CI = 1.063–55.650; p = 0.04) or APACHE-II (OR = 11.858; 95% CI = 1.524–92.273; p = 0.02), the allele HLA-C*01 after controlling for SOFA (OR = 11.182; 95% CI = 1.053–118.700; p = 0.04) or APACHE-II (OR = 17.604; 95% CI = 1.629–190.211; p = 0.02), and the allele HLA-DQB1*04 after controlling for SOFA (OR = 9.963; 95% CI = 1.235–80.358; p = 0.03). Conclusions The new finding from our preliminary study of small sample size was that HLA genetic polymorphisms could be associated with COVID-19 mortality; however, studies with a larger sample size before definitive conclusions can be drawn.

BackgroundUnderstanding the determinants of long-term immune responses to SARS-CoV-2 and the concurrent impact of vaccination and emerging variants of concern will guide optimal strategies to achieve global protection against the COVID-19 pandemic.MethodsA prospective cohort of 332 COVID-19 patients was followed beyond one year. Plasma neutralizing activity was evaluated using HIV-based reporter pseudoviruses expressing different SARS-CoV-2 spikes and was longitudinally analyzed using mixed-effects models.FindingsLong-term neutralizing activity was stable beyond one year after infection in mild/asymptomatic and hospitalized participants. However, longitudinal models suggest that hospitalized individuals generate both short- and long-lived memory B cells, while outpatient responses were dominated by long-lived B cells. In both groups, vaccination boosted responses to natural infection, although viral variants, mainly B.1.351, reduced the efficacy of neutralization. Importantly, despite showing higher neutralization titers, hospitalized patients showed lower cross-neutralization of B.1.351 variant compared to outpatients. Multivariate analysis identified severity of primary infection as the factor that independently determines both the magnitude and the inferior cross-neutralization activity of long-term neutralizing responses.ConclusionsNeutralizing response induced by SARS-CoV-2 is heterogeneous in magnitude but stable beyond one year after infection. Vaccination boosts these long-lasting natural neutralizing responses, counteracting the significant resistance to neutralization of new viral variants. Severity of primary infection determines higher magnitude but poorer quality of long-term neutralizing responses.

Aims This trial aimed to evaluate the safety and efficiency of a common and simplified protocol for the surveillance of cardiac implantable electronic devices based on remote monitoring (RM) in patients with pacemakers (PMs) and implantable cardiac defibrillators (ICDs) for at least 24 months. Methods and results The RM-ALONE is a multicentre prospective trial that randomly assigned 445 patients in two groups, both followed by RM: the home monitoring-only (HMo) based on RM + remote interrogations (RIs) every 6 months and the HM + IO that adds in-office evaluations every 6 months to RM. Four hundred and forty-five patients were enrolled in the study, 294 PMs and 151 ICDs recipients. In the HMo group, 20% of patients experienced ≥1 major adverse cardiac event (MACE) vs. 19.5% in HM + IO group (P = 0.006 for non-inferiority). The proportion of patients with a PM/ICD who experienced ≥1 MACE was 15.2/29.3% in HMo group and 16.1/26.3% in HM + IO group (hazard ratio 0.95/1.15, 95% confidence interval 0.53–1.70/0.62–2.10). There were 789 in-office evaluations (136 in the HMo and 653 in the HM + IO; P Conclusion The RM-ALONE protocol common for ICD and PM surveillance, consisting of RM + RI every 6 months has proven safe and efficient in reducing hospital visits and staff workload.

To the Editor,In this journal we recently reported our study on serum levels of soluble Fas Ligand (sFasL), a ligand that activates extrinsic apoptosis pathway, in septic patients [1]. At diagnosis...

The protective effect of neutralizing antibodies in SARS-CoV-2 infected individuals is not yet well defined. To address this issue, we have analyzed the kinetics of neutralizing antibody responses and their association with disease severity. Between March and May 2020, the prospective KING study enrolled 72 COVID-19+ participants grouped according to disease severity. SARS-CoV-2 infection was diagnosed by serological and virological tests. Plasma neutralizing responses were assessed against replicative virus and pseudoviral particles. Multiple regression and non-parametric tests were used to analyze dependence of parameters. The magnitude of neutralizing titers significantly increased with disease severity. Hospitalized individuals developed higher titers compared to mild-symptomatic and asymptomatic individuals, which together showed titers below the detection limit in 50% of cases. Longitudinal analysis confirmed the strong differences in neutralizing titers between non-hospitalized and hospitalized participants and showed rapid kinetics of appearance of neutralizing antibodies (50% and 80% of maximal activity reached after 11 and 17 days after symptoms onset, respectively) in hospitalized patients. No significant impact of age, gender or treatment on the neutralizing titers was observed in this limited cohort. These data identify a clear association of humoral immunity with disease severity and point to immune mechanisms other than antibodies as relevant players in COVID-19 protection. This work was partially funded by Grifols, the Departament de Salut of the Generalitat de Catalunya (Grant DSL0016 to JB and Grant DSL015 to JC), the Spanish Health Institute Carlos III (Grant PI17/01518 and PI18/01332 to JC) and the crowdfunding initiatives #joemcorono, BonPreu/Esclat and Correos. The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript. EP was supported by a doctoral grant from National Agency for Research and Development (ANID)—Formation of Advanced Human Capital Program, Becas Chile: Grant 72180406. We are deeply grateful to all participant and to the technical staff of IrsiCaixa for sample processing. We also thank Daniel Pérez-Zsolt and Jordana Muñoz-Basagoiti for assistance with ACE-2 expressing 293T cell culture. Peer Reviewed "Article signat per 26 autors/es: Benjamin Trinité, Ferran Tarrés-Freixas, Jordi Rodon, Edwards Pradenas, Víctor Urrea, Silvia Marfil, María Luisa Rodríguez de la Concepción, Carlos Ávila-Nieto, Carmen Aguilar-Gurrieri, Ana Barajas, Raquel Ortiz, Roger Paredes, Lourdes Mateu, Alfonso Valencia, Víctor Guallar, Lidia Ruiz, Eulàlia Grau, Marta Massanella, Jordi Puig, Anna Chamorro, Nuria Izquierdo-Useros, Joaquim Segalés, Bonaventura Clotet, Jorge Carrillo, Júlia Vergara-Alert & Julià Blanco"

The ideal treatment of pelvis bone metastases may be complex and involve multimodality treatment approaches to achieve optimal outcomes. The chapter describes the treatments indications of these patients. It is described from nonoperative treatments, through minimally invasive palliative procedures until reaching the surgical treatment, emphasizing types of pelvis resection and indications for surgical reconstruction of the acetabulum.

There are scarce data on soluble Fas Ligand (sFasL), one of the main ligands that activate the apoptosis extrinsic pathway, in septic patients. In a small study of septic children were found higher plasma sFasL levels in non-survivors compared with survivors; however, an association between blood sFasL levels and mortality controlling for sepsis severity was not stablished due to the small sample size of the study. Therefore, the main objective of this study was to determine whether there is an association between blood sFasL concentrations and mortality in septic patients controlling for sepsis severity.Thirty-day non-surviving patients (The main new finding from our study was that serum sFasL concentrations were associated with mortality in septic patients controlling for sepsis severity. Highlights Blood sFasL concentrations were higher in non-survivor than in survivor patients. There is an association between blood sFasL concentrations and mortality in septic patients. Blood sFasL concentrations could predict mortality of septic patients.

OBJECTIVE To estimate the trends of fall-related hospitalization, mortality, and lethality among older adults in Brazil and regions. METHODS This is a descriptive study based on data from the Hospital Information System of the Brazilian Unified Health System. We included records of every older adult, aged 60 years or older, hospitalized for accidental fall from January, 1998 to November, 2015 in all Brazilian regions. We selected the codes E885, E886, E880, E884, E884 from the International Classification of Diseases, 9th revision, and W01, W03, W10, W17, W18 from the 10th revision, and calculated fall-related hospitalization and mortality rates per 100,000 inhabitants, as well as lethality. To estimate trends, we applied the Prais-Winsten regression for time series analysis. RESULTS During the period, 1,192,829 fall-related hospitalizations occurred, among which 54,673 had a fatal outcome; lethality was 4.5%. Hospitalization rates showed upward trends, with seasonality, in Brazil (11%), and in the Northeast (44%), Midwest (13%), and South regions (14%). The North showed a decreasing hospitalization rate (48%), and the Southeast a stationary one (3%). CONCLUSIONS In Brazil, fall-related hospitalizations, mortality, and lethality among older adults showed an upward trend from 1998 to 2015, with seasonal peaks in the second and third quarters. Considering we are in plain demographic transition, to improve hospital healthcare and encourage falls prevention programs among older adults is essential. RESUMO OBJETIVO Estimar as tendências de internação, mortalidade e letalidade por quedas em idosos no Brasil e regiões. MÉTODOS Estudo descritivo realizado a partir de dados do Sistema de Informações Hospitalares do Sistema Único de Saúde. Foram incluídos os registros de todos os idosos, a partir de 60 anos, internados por quedas acidentais entre janeiro de 1998 e novembro de 2015 em todas regiões do Brasil. Foram selecionados os códigos E885, E886, E880, E884, E888 e W01, W03, W10, W17, W18 da Classificação Internacional de Doenças (CID), 9ª e 10ª revisão respectivamente, e calculadas as taxas de internação e mortalidade por quedas por 100.000 habitantes, além da letalidade. Para cálculo de tendências, usou-se o procedimento de Prais-Winsten de autorregressão para análise de séries temporais. RESULTADOS Foram realizadas 1.192.829 internações por quedas no período, ocorreram 54.673 desfechos fatais, e a letalidade foi de 4,5%. As taxas de internação apresentaram tendências crescentes, com sazonalidade, no Brasil e nas regiões Nordeste, Centro-Oeste e Sul (taxas de crescimento de 11%, 44%, 13% e 14%, respectivamente). No Norte, a taxa de internação foi decrescente, e no Sudeste foi estacionária (taxas de crescimento: 48% e 3%). CONCLUSÕES Houve tendência crescente de internações, mortalidade e letalidade por quedas em idosos entre 1998 e 2015 no Brasil, com picos sazonais no segundo e terceiro trimestres. É necessário aprimorar tanto a assistência hospitalar quanto incentivar programas de prevenção de quedas em idosos, visto que estamos em plena transição demográfica.

Scarce data on Fas, one of the main receptors that activates the apoptosis extrinsic pathway, in septic patients exists. Higher blood soluble Fas (sFas) concentrations in non-survivor septic patients compared with survivors have been found in small studies; however, the association of blood sFas concentrations with mortality controlling for sepsis severity has not been stablished due to this small sample size in those studies. Thus, our main objective study was to determine whether an association between blood sFas concentrations and sepsis mortality controlling for sepsis severity exists.We included septic patients in this observational and prospective study carried out in three Spanish Intensive Care Units. We obtained serum samples at sepsis diagnosis sepsis for sFas levels determination.Thirty-day non-surviving patients (n=85) compared to surviving patients (n=151) had higher serum sFas levels (p0.001). We found in multiple logistic regression analysis an association of serum sFas levels with mortality controlling for age and SOFA (OR=1.004; 95% CI=1.002-1.006; p0.001), and for age and APACHE-II (OR=1.004; 95% CI=1.002-1.006; p0.001). Serum sFas levels showed and area under the curve for mortality prediction of 71% (95% CI=65-71%; p0.001). Kaplan-Meier analysis showed higher mortality rate in patients with serum sFas levels83.5ng/mL (Hazard ratio=3.2; 95% CI=2.1-5.0; p0.001).That an association between blood sFas concentrations and sepsis mortality controlling for sepsis severity exists was our main new finding study.

Highlights • Non-surviving showed higher RDW than surviving patients. • There is an association between RDW and mortality. • RDW could be used as mortality biomarker., Purpose We have previously reported an association between high red blood cell distribution width (RDW) and mortality in septic and brain infarction patients. However, no association between RDW and mortality in coronavirus disease 2019 (COVID-19) patients has been reported so far; thus, the objective of this study was to determine if that association exists. Methods Prospective and observational study carried out in 8 Intensive Care Units from 6 hospitals of Canary Islands (Spain) including COVID-19 patients. We recorded RDW at ICU admission and 30-day survival. Results We found that patients who did not survive (n = 25) compared to surviving patients (n = 118) were older (p = 0.004), showed higher RDW (p = 0.001), urea (p

OBJETIVO: Estimar a prevalência de quedas acidentais em mulheres e identificar possíveis associações de variáveis sociodemográficas, clínicas e de hábitos de vida com as quedas, em 2007 e 2014. MÉTODOS: Foram realizados dois estudos transversais, em 2007 e 2014, dentro do Projeto de Saúde de Pindamonhangaba (PROSAPIN), com mulheres com idades variando de 35 a 75 anos. As amostras probabilísticas foram selecionadas dentre as mulheres residentes no município e participantes da Estratégia Saúde da Família. A coleta de dados incluiu: entrevista face a face, exame antropométrico e exame sanguíneo. A variável de desfecho “Sofreu queda nos últimos seis meses?” foi levantada durante a entrevista. Foram estimadas as prevalências de quedas em 2007 e 2014 por ponto e intervalo de confiança de 95% (IC95%). Modelos de regressão logística múltipla foram construídos para identificar a associação das variáveis independentes e a ocorrência de quedas para cada ano a partir da odds ratio (OR). Utilizou-se o software Stata 14.0 para análise estatística. RESULTADOS: A s p revalências d e q uedas a cidentais f oram: 17,6% ( IC95% 14,9–20,5) e m 2007 e 17,2% (IC95% 14,8–19,8) em 2014. Em 2007 os fatores associados a quedas foram: idade de 50–64 anos (OR = 1,81; IC95% 1,17–2,80), ensino médio (OR = 1,76; IC95% 1,06–2,93), hiperuricemia (OR = 3,74; IC95% 2,17–6,44), depressão (OR = 2,07; IC95% 1,31–3,27), sono ruim (OR = 1,78; IC95% 1,12–2,82) e sonolência diurna (OR = 1,86; IC95% 1,16–2,99). Em 2014 permaneceram: idade de 50–64 anos (OR = 1,64; IC95% 1,04–2,58), hiperuricemia (OR = 1,91; IC95% 1,07–3,43) e depressão (OR = 1,56; IC95% 1,02–2,38), acrescidos da síndrome metabólica (OR = 1,60; IC95% 1,03–2,47) e da dor musculoesquelética (OR = 1,81; IC95% 1,03–3,18). CONCLUSÕES: As quedas ocorrem de maneira importante em mulheres a partir dos 50 anos, indicando que não são restritas a idosos e que há necessidade de iniciar medidas preventivas mais precocemente. Os dois estudos mostraram magnitudes semelhantes de ocorrência de quedas acidentais e reforçaram sua multifatorialidade. Além disso, a hiperuricemia pode ser um potencial novo fator associado a quedas.

Abusive head trauma (AHT) is an extreme form of physical abuse that is produced by abruptly shaking an infant or toddler.To describe the direct economic cost of care during hospitalization of 14 children with confirmed diagnosis of AHT in a pediatric hospital.Analysis of the cost of disease in patients with AHT attended to between 2001 and 2010. Partial direct economic cost of medical care (days of hospital stay, laboratory tests and imaging studies, surgical procedures and subspecialist consultations) was calculated adjusting for inflation, with year 2001 taken as base year. Patients were classified in three groups (moderate, severe and fatal AHT). Descriptive and sensitivity analysis was carried out.Patients with severe AHT generated higher medical care costs ($105,794.88 ± 33,201.91) in comparison with the group of moderate ($37,012.95, ± 7,154.87) and fatal AHT ($18,595.04 ± 6424.47) (p0.05). Total cost was $665,467.98 Mexican pesos ($71,249.25 international dollars).Total cost for the 14 patients was an elevated figure, as in other parts of the world. The direct economic cost is closely related to the severity of the clinical presentation.El trauma craneal no accidental (TCNA) es una forma extrema de abuso físico que se produce por la sacudida brusca de un lactante o preescolar.Describir el costo económico directo de la atención durante la hospitalización de 14 niños con diagnóstico confirmado de TCNA en un hospital pediátrico.Análisis del costo de la enfermedad en pacientes con TCNA, atendidos entre 2001 y 2010. Se realizó análisis descriptivo y de sensibilidad. Se calculó costo económico directo parcial de la atención médica (días de estancia hospitalaria, exámenes de laboratorio y gabinete, procedimientos quirúrgicos y consultas por subespecialista), ajustado por la inflación, se tomó como año base 2001. Los pacientes se clasificaron en tres grupos: TCNA moderado, severo y fatal.Los pacientes con TCNA severo generaron mayor costo en la atención médica ($105 794.88 ± 33 201.91), en comparación con el grupo con TCNA moderado ($37 012.95 ± 7154.87) y fatal ($18 595.04 ± 6424.47) (p0.05). El costo total fue de 665 467.98 pesos mexicanos (71 249.25 dólares internacionales).El costo total de los 14 pacientes fue una cifra elevada como en otras partes del mundo. El costo económico directo se relaciona estrechamente con la gravedad del cuadro clínico.

Objective To review the chemistry, pharmacology, microbiology, pharmacokinetics, pharmacodynamics, clinical efficacy, safety, dosing, and administration of ceftazidime/avibactam (CAZ/AVI). Data sources A search of PubMed using the terms "ceftazidime," "avibactam," "NXL104," and "AVE1330A" was performed. The manufacturer's website was also reviewed to further identify relevant information. Study selection All English-language articles from 2004 to May 2015 appearing in these searches were reviewed for relevance to this paper. In addition, their bibliographies were reviewed to identify any articles not identified in the searches. Data synthesis CAZ/AVI is a new cephalosporin β-lactamase inhibitor combination with a spectrum of activity targeted against Gram-negative organisms including Enterobacteriaceae and Pseudomonas aeruginosa. The dosing regimen is 2.5 g every eight hours administered via IV infusion over two hours for 5 to 14 days. The dosing regimen should be adjusted based on renal function. A phase II trial has demonstrated that clinical cure rates with CAZ/AVI plus metronidazole are comparable to those with meropenem in the treatment of adults with complicated intra-abdominal infections. Another phase II clinical trial has demonstrated that clinical cure rates with CAZ/AVI are comparable to those with imipenem/cilastatin for the treatment of adults with complicated urinary tract infections (cUTIs). CAZ/AVI has a side effect profile similar to that of cephalosporins and carbapenems. Conclusion CAZ/AVI has a favorable efficacy and safety profile in the treatment of adults with complicated intra-abdominal infections or cUTIs. Further research is needed to refine its role, particularly for the treatment of multi-drug-resistant Gram-negative infections.

Objective: To analyze the influence of a kinesiotherapeutic program for the prevention of falls on the cardiovascular function in the elderly. Materials and Methods: The sample consisted of 18 community-living elderly with a mean age of 73.5 ± 8.8 years (14 women; 4 men) who participated in an exercise program for flexibility, strength, balance and proprioception. We measured systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR) and double product (DP) before and after exercise. The coefficient of variation (CV) of the measures was used, as well as paired t test and Wilcoxon test for comparison between baseline and endpoint after exercise. Results: In 10 sessions, there was an average CV lower than 10% for SBP, DBP and HR. As an acute effect of exercise, there was a significant increase in SBP and DBP and a significant decrease in HR. Comparing the data of the 1st session of exercise to those of the 10th session, we observed that the values of the variables tended to be reduced (except the initial DBP), but with significance only for the final DP. There was a greater reduction in SBP, HR and DP over 20 sessions compared to 10 sessions. Conclusion: The program for the prevention of falls provided chronic effects that are beneficial to cardiovascular function in the elderly, which may also be indicated for the management of cardiovascular diseases. DESCRIPTORS: Aged. Exercises. Arterial Pressure. Heart Rate.