Corticosteroids and tocilizumab reduce in-hospital mortality in severe COVID-19 pneumonia: a retrospective study in a Spanish hospital.

BACKGROUND: There is an urgent need to reduce mortality of COVID-19. We examined if corticosteroids and tocilizumab reduce risk for death in patients with severe pneumonia caused by SARS-CoV-2. METHODS: A retrospective cohort study was performed in a single university hospital. All adult patients admitted with confirmed severe COVID-19 pneumonia from 9 March to 9 April 2020 were included. Severe pneumonia was defined as multi-lobar or bilateral pneumonia and a ratio of oxygen saturation by pulse oximetry to the fraction of inspired oxygen (SpFi)<315. All patients received antiviral and antibiotic treatment. From March 26, patients also received immunomodulatory treatment with corticosteroids (methylprednisolone 250 mg/day for 3 days), or tocilizumab or both. In-hospital mortality in the entire cohort and in a 1:1 matched cohort sub-analysis was evaluated. RESULTS: 255 patients were included, 118 received only antiviral and antibiotic treatment while 137, admitted after March 26, also received immunomodulators. In-hospital mortality of patients on immunomodulatory treatment was significantly lower than in those without [47/137(34.3%) vs. 69/118(58.5%), (p < .001)]. The risk of death was 0.44 (CI, 0.26-0.76) in patients receiving corticosteroids alone and 0.292 (CI, 0.18-0.47) in those treated with corticosteroids and tocilizumab. In the sub-analysis with 202 matched patients, the risk of death was 0.356 (CI 0.179-0.707) in patients receiving corticosteroids alone and 0.233 (0.124-0.436) in those treated with the combination. CONCLUSIONS: Combined treatment with corticosteroids and tocilizumab reduced mortality with about 25% in patients with severe COVID-19 pneumonia. Corticosteroids alone also resulted in lower in-hospital mortality rate compared to patients receiving only antiviral and antibiotic treatment. Corticosteroids alone or combined with tocilizumab may be considered in patients with severe COVID-19 pneumonia.

Preoperative oral antibiotic prophylaxis reduces Pseudomonas aeruginosa surgical site infections after elective colorectal surgery: a multicenter prospective cohort study.

BACKGROUND: Healthcare-associated infections caused by Pseudomonas aeruginosa are associated with poor outcomes. However, the role of P. aeruginosa in surgical site infections after colorectal surgery has not been evaluated. The aim of this study was to determine the predictive factors and outcomes of surgical site infections caused by P. aeruginosa after colorectal surgery, with special emphasis on the role of preoperative oral antibiotic prophylaxis. METHODS: We conducted an observational, multicenter, prospective cohort study of all patients undergoing elective colorectal surgery at 10 Spanish hospitals (2011-2014). A logistic regression model was used to identify predictive factors for P. aeruginosa surgical site infections. RESULTS: Out of 3701 patients, 669 (18.1%) developed surgical site infections, and 62 (9.3%) of these were due to P. aeruginosa. The following factors were found to differentiate between P. aeruginosa surgical site infections and those caused by other microorganisms: American Society of Anesthesiologists' score III-IV (67.7% vs 45.5%, p = 0.001, odds ratio (OR) 2.5, 95% confidence interval (95% CI) 1.44-4.39), National Nosocomial Infections Surveillance risk index 1-2 (74.2% vs 44.2%, p < 0.001, OR 3.6, 95% CI 2.01-6.56), duration of surgery ≥75thpercentile (61.3% vs 41.4%, p = 0.003, OR 2.2, 95% CI 1.31-3.83) and oral antibiotic prophylaxis (17.7% vs 33.6%, p = 0.01, OR 0.4, 95% CI 0.21-0.83). Patients with P. aeruginosa surgical site infections were administered antibiotic treatment for a longer duration (median 17 days [interquartile range (IQR) 10-24] vs 13d [IQR 8-20], p = 0.015, OR 1.1, 95% CI 1.00-1.12), had a higher treatment failure rate (30.6% vs 20.8%, p = 0.07, OR 1.7, 95% CI 0.96-2.99), and longer hospitalization (median 22 days [IQR 15-42] vs 19d [IQR 12-28], p = 0.02, OR 1.1, 95% CI 1.00-1.17) than those with surgical site infections due to other microorganisms. Independent predictive factors associated with P. aeruginosa surgical site infections were the National Nosocomial Infections Surveillance risk index 1-2 (OR 2.3, 95% CI 1.03-5.40) and the use of oral antibiotic prophylaxis (OR 0.4, 95% CI 0.23-0.90). CONCLUSIONS: We observed that surgical site infections due to P. aeruginosa are associated with a higher National Nosocomial Infections Surveillance risk index, poor outcomes, and lack of preoperative oral antibiotic prophylaxis. These findings can aid in establishing specific preventive measures and appropriate empirical antibiotic treatment.

Multistate modelling to estimate excess length of stay and risk of death associated with organ/space infection after elective colorectal surgery.

BACKGROUND: Accounting for time-dependency and competing events are strongly recommended to estimate excess length of stay (LOS) and risk of death associated with healthcare-associated infections. AIM: To assess the effect of organ/space (OS) surgical site infection (SSI) on excess LOS and in-hospital mortality in patients undergoing elective colorectal surgery (ECS). METHODS: A multicentre prospective adult cohort undergoing ECS, January 2012 to December 2014, at 10 Spanish hospitals was used. SSI was considered the time-varying exposure and defined as incisional (superficial and deep) or OS. Discharge alive and death were the study endpoints. The mean excess LOS was estimated using a multistate model which provided a weighted average based on the states patients passed through. Multivariate Cox regression models were used to assess the effect of OS-SSI on risk of discharge alive or in-hospital mortality. FINDINGS: Of 2778 patients, 343 (12.3%) developed SSI: 194 (7%) OS-SSI and 149 (5.3%) incisional SSI. Compared to incisional SSI or no infection, OS-SSI prolonged LOS by 4.2 days (95% confidence interval (CI): 4.1-4.3) and 9 days (8.9-9.1), respectively, reduced the risk of discharge alive (adjusted hazard ratio (aHR): 0.36 (95% CI: 0.28-0.47) and aHR: 0.17 (0.14-0.21), respectively), and increased the risk of in-hospital mortality (aHR: 8.02 (1.03-62.9) and aHR: 10.7 (3.7-30.9), respectively). CONCLUSION: OS-SSI substantially extended LOS and increased risk of death in patients undergoing ECS. These results reinforce OS-SSI as the SSI with the highest health burden in ECS.

Predictive factors for early- and late-onset surgical site infections in patients undergoing elective colorectal surgery. A multicentre, prospective, cohort study.

BACKGROUND: Surgical site infections (SSIs) are the leading cause of healthcare-associated infections in acute care hospitals in Europe. However, the risk factors for the development of early-onset (EO) and late-onset (LO) SSI have not been elucidated. AIM: This study investigated the predictive factors for EO-SSI and LO-SSI in a large cohort of patients undergoing colorectal surgery. METHODS: We prospectively followed-up adult patients undergoing elective colorectal surgery in 10 hospitals (2011-2014). Patients were divided into three groups: EO-SSI, LO-SSI, or no infection (no-SSI). The cut-off defining EO-SSI and LO-SSI was seven days (median time to SSI development). Different predictive factors for EO-SSI and LO-SSI were analysed, comparing each group with the no-SSI patients. FINDINGS: Of 3701 patients, 320 (8.6%) and 349 (9.4%) developed EO-SSI and LO-SSI, respectively. The rest had no-SSI. Patients with EO-SSI were mostly males, had colon surgery and developed organ-space SSI whereas LO-SSI patients frequently received chemotherapy or radiotherapy and had incisional SSI. Male sex (odds ratio (OR): 1.92; P < 0.001), American Society of Anesthesiologists' physical status >2 (OR: 1.51; P = 0.01), administration of mechanical bowel preparation (OR: 0.7; P = 0.03) and stoma creation (OR: 1.95; P < 0.001) predicted EO-SSI whereas rectal surgery (OR: 1.43; P = 0.03), prolonged surgery (OR: 1.4; P = 0.03) and previous chemotherapy (OR: 1.8; P = 0.03) predicted LO-SSI. CONCLUSION: We found distinctive predictive factors for the development of SSI before and after seven days following elective colorectal surgery. These factors could help establish specific preventive measures in each group.

Risk factors, clinical characteristics, and outcomes of invasive fungal infections in solid organ transplant recipients.

BACKGROUND: Invasive fungal infection (IFI) is an important cause of morbidity and mortality among solid organ transplant (SOT) recipients. We sought to assess risk factors, clinical characteristics, and current outcomes of IFI in SOT recipients. METHODS: We reviewed all episodes of IFI occurring among SOT recipients in a university hospital from 2008 to 2011. To determine risk factors for IFI we carried out a matched case-control study (1:2 ratio). Control subjects were matched for transplant type and timing. RESULTS: We documented 20 episodes of IFI among 744 SOT recipients (2.7%). Sixty-five percent of cases were proven IFI and 35% were probable IFI. The types of IFI documented were aspergillosis in 8 cases, candidiasis in 7, pneumocystosis in 3, Emmonsia species in infection 1, and disseminated cryptococcosis in 1. Ninety-nine percent of the patients had received a prior antibiotic therapy (3 months), 40% presented allograft rejection (3 months), and 40% had prior kidney injury. Complications of IFI included septic shock (50%), respiratory failure (55%), multiple-organ dysfunction (55%), and intensive care unit (ICU) admission (50%). Median days from transplantation to diagnosis was 103 for candidiasis (range, 27-4644) and 1195 for aspergillosis (range, 0-4319). In a comparison of case patients with 40 matched control subjects, case patients more frequently presented prior ICU stay (3 months; P = .05), hemodialysis requirement (P = .02), receipt of high-dose prednisone (6 months; P = .006), and prior antibiotic therapy (P < .001). Prior use of antibiotic treatment was the only risk factor for IFI (odds ratio [OR] 93; 95% confidence interval [CI], 8.3-1042). Case-fatality rate was 60%. CONCLUSIONS: In our recent experience, 2.7% of SOT recipients developed IFI, mainly aspergillosis followed by candidiasis. Prior ICU admission, hemodialysis, receipt of high-dose prednisone, and prior antibiotic use were more frequent in cases when compared with control subjects, with the latter factor being the only independent risk factor for developing IFI. Case-fatality rate was high (60%).

Moral dilemmas in cognitive neuroscience of moral decision-making: a principled review.

Moral dilemma tasks have been a much appreciated experimental paradigm in empirical studies on moral cognition for decades and have, more recently, also become a preferred paradigm in the field of cognitive neuroscience of moral decision-making. Yet, studies using moral dilemmas suffer from two main shortcomings: they lack methodological homogeneity which impedes reliable comparisons of results across studies, thus making a metaanalysis manifestly impossible; and second, they overlook control of relevant design parameters. In this paper, we review from a principled standpoint the studies that use moral dilemmas to approach the psychology of moral judgment and its neural underpinnings. We present a systematic review of 19 experimental design parameters that can be identified in moral dilemmas. Accordingly, our analysis establishes a methodological basis for the required homogeneity between studies and suggests the consideration of experimental aspects that have not yet received much attention despite their relevance.

[Congenital cytomegalovirus infection]. / Infección congénita por citomegalovirus.

INTRODUCTION: Cytomegalovirus (CMV) is the most frequent cause of intrauterine infection and an important cause of auditory system damage and mental retardation in humans. Clinical presentation varies from asymptomatic form to lethal systemic dissemination. OBJECTIVES: To describe clinical and laboratories manifestations, age at the moment of diagnostic, treatment and diagnostic test used in congenital cytomegalovirus infection. POPULATION, MATERIAL AND METHODS: Observational, retrospective and descriptive study. Clinical histories of congenital CMV infected infants evaluated by Infectology Department of the Hospital General de Niños Dr. Ricardo Gutiérrez between January 2002 and December 2006 were analyzed. RESULTS: Seventeen patients were evaluated. Mean age at diagnosis was 2.6 months. The most frequent symptom/sign were hepato-splenomegaly (76 %), jaundice (47 %), petechiae and hearing deficit (41 %). Anemia (53 %) and thrombocytopenia (40 %) were the most common laboratory abnormalities. Diagnosis was made exclusively by polymerase chain reaction (PCR)-CMV in one third of the patients, whereas one third was diagnosed by serology and the other third for both test. Five patients received ganciclovir as treatment. Only one had neutropenia. CONCLUSIONS: Differential diagnosis of all newborns with hepatoesplenomegaly, jaundice and petechiae and anemia and/or thrombocytopenia must include congenital cytomegalo-virus infection. Early diagnosis allows a prompt intervention and a strict audiological follow up.

Infección congénita por citomegalovirus / Congenital cytomegalovirus infection

Introducción: El citomegalovirus (CMV) causa la infección intrauterina más frecuente y es una importante causa de retraso mental e hipoacusia neurosensorial. Su presentación clínica varía entre la forma asintomática y la diseminación multi-sistémica letal. Objetivos: Describir las manifestaciones clínicas y bioquímicas, edad en el momento del diagnóstico, metodología diagnóstica empleada y tratamiento utilizado en niños infectados en forma congénita por CMV. Población, material y métodos: Se trata de un estudio observacional, retrospectivo y descriptivo. Se revisaron las historias clínicas de niños menores de 6 meses con diagnóstico de infección congénita por CMV atendidos en el Servicio de Infectología del Hospital de Niños Dr. Ricardo Gutiérrez entre enero de 2002 y diciembre de 2006. Las variables en estudio fueron las manifestaciones clínicas y bioquímicas, la edad en el momento del diagnóstico, la metodología diagnóstica empleada y el tratamiento utilizado. Resultados: Se evaluaron 17 pacientes. La edad media en el momento del diagnóstico fue de 2,6 meses. La principal manifestación clínica fue la hepatosplenomegalia (76 %), seguida de ictericia (47 %), petequias e hipoacusia (41 %). La anemia (53 %) y la trombocitopenia (40 %) fueron las alteraciones bioquímicas más frecuentes. En un tercio de los casos se llegó al diagnóstico exclusivamente mediante reacción en cadena de la polimerasa (PCR)-CMV, en otra tercera parte sólo por serología y en el tercio restante mediante el uso de ambas pruebas. Cinco pacientes recibieron ganciclovir y sólo uno presentó neutrocitopenia como complicación. Conclusiones: El diagnóstico diferencial de todo recién nacido con hepatosplenomegalia, ictericia y petequias, así como con anemia y trombocitopenia debe incluir la infección congénita por CMV. La oportunidad diagnóstica permite una intervención precoz y un estrecho seguimiento audiológico (AU)

Introduction: Cytomegalovirus (CMV) is the most frequent cause of intrauterine infection and an important cause of auditory system damage and mental retardation in humans. Clinical presentation varies from asymptomatic form to lethal systemic dissemination. Objectives: To describe clinical and laboratories manifestations, age at the moment of diagnostic, treatment and diagnostic test used in congenital cytomegalovirus infection. Population, material and methods: Observational, retrospective and descriptive study. Clinical histories of congenital CMV infected infants evaluated by Infectology Department of the Hospital General de Niños Dr. Ricardo Gutiérrez between January 2002 and December 2006 were analyzed. Results: Seventeen patients were evaluated. Mean age at diagnosis was 2.6 months. The most frequent symptom/sign were hepato-splenomegaly (76 %), jaundice (47 %), petechiae and hearing deficit (41 %). Anemia (53 %) and thrombocytopenia (40 %) were the most common laboratory abnormalities. Diagnosis was made exclusively by polymerase chain reaction (PCR)-CMV in one third of the patients, whereas one third was diagnosed by serology and the other third for both test. Five patients received ganciclovir as treatment. Only one had neutropenia. Conclusions: Differential diagnosis of all newborns with hepatoesplenomegaly, jaundice and petechiae and anemia and/or thrombocytopenia must include congenital cytomegalo-virus infection. Early diagnosis allows a prompt intervention and a strict audiological follow up (AU)

[Longitudinal study in children with the nephrotic syndrome and minimal glomerular lesion]. / Estudio longitudinal en niños con síndrome nefrótico y lesión glomerular mínima.

Twenty-one children with idiopathic nephrotic syndrome and minimal changes on renal biopsy were followed during all the disease. The average of follow-up was 37 months, with a range from 12 to 124 months. Recurrent proteinuria was the most important feature during the follow-up; 14 out of the patients showed frequent relapses, but only 2 patients showed major complication (peritonitis, septicemia) during relapses. Frequent relapses appeared most frequently in patients who began the disease before their fourth birthday, showed allergic history, had hypertension and red blood cells in urine, or had recurrent infections and finally, in those where proteinuria reappeared soon after prednisone therapy was ended. Prednisone alone was successful to induce remission, but it did not prevent frequent relapses. The association clorambucil-prednisone allowed lengthening of the period of remission and possibly for this reason the rate of relapses fell during the first 37 months of the follow-up. There are no signs which permit to predict the length of the disease and the frequent relapses can occur even after many years from the beginning of the disease. Special care of these patients avoids major complications.