Correction: "Acute kidney injury in critically ill patients with COVID-19: The AKICOV multicenter study in Catalonia".

[This corrects the article DOI: 10.1371/journal.pone.0284248.].

Identification of spread after deliberated intraneural injection in five mammalian species: not all animal models and needle types are valid for studying the effect of intraneural injections in humans.

INTRODUCTION: This research endeavors to investigate the phenomenon of intraneural spread across distinct locations: subcircumneurium, extrafascicular intraneural, intrafascicular intraneural, and intraperineurium after deliberate intraneural injections across five mammalian species. The study also aims to propose determinants influencing this spread. Furthermore, the investigation strives to ascertain the optimal animal species and needle configuration for extrapolating intraneural injection outcomes to human contexts. METHODS: This study examined 60 sciatic nerves from 30 fresh and untreated cadavers of rats, rabbits, dogs, pigs, and sheep. The specimens were organized into five groups, each comprising an equal number of nerves. Histological assessments were performed on 30 nerves, involving fascicle metrics. The remaining 30 nerves underwent intentional intraneural injections, facilitated by 19G and 23G needles under ultrasound and direct visualization guidance.Heparinized erythrocytes combined with a methylene blue solution were used as a marker to analyze the extent and patterns of intraneural spread. Needle orifice measurements were obtained, and these data were overlaid onto images of both nerves and needles. This enabled a comparative evaluation of sizes and an assessment of marker diffusion. RESULTS: The findings indicated that sciatic nerves in rats, rabbits, and dogs were oligofascicular, characterized by larger fascicles, whereas pigs and sheep exhibited polyfascicular nerves comprised of numerous smaller fascicles. Fascicular diameters were variable across species, with dogs presenting the largest measurements. While intraneural spread was observed and documented, intrafascicular marker spreading was rare, occurring only in one rabbit specimen. Needle orifice attributes were scrutinized and visually depicted. CONCLUSIONS: Despite the formidable challenges associated with the practical realization of intrafascicular injection, the utilization of animal models possessing monofascicular or oligofascicular nerves, such as rats, rabbits, and dogs, in conjunction with needles featuring aperture dimensions surpassing those of the fascicles, likely contributes to the compromised reliability of investigations into intraneural injection outcomes.

"Acute kidney injury in critically ill patients with COVID-19: The AKICOV multicenter study in Catalonia".

This study describes the incidence, evolution and prognosis of acute kidney injury (AKI) in critical COVID-19 during the first pandemic wave. We performed a prospective, observational, multicenter study of confirmed COVID-19 patients admitted to 19 intensive care units (ICUs) in Catalonia (Spain). Data regarding demographics, comorbidities, drug and medical treatment, physiological and laboratory results, AKI development, need for renal replacement therapy (RRT) and clinical outcomes were collected. Descriptive statistics and logistic regression analysis for AKI development and mortality were used. A total of 1,642 patients were enrolled (mean age 63 (15.95) years, 67.5% male). Mechanical ventilation (MV) was required for 80.8% and 64.4% of these patients, who were in prone position, while 67.7% received vasopressors. AKI at ICU admission was 28.4% and increased to 40.1% during ICU stay. A total of 172 (10.9%) patients required RRT, which represents 27.8% of the patients who developed AKI. AKI was more frequent in severe acute respiratory distress syndrome (ARDS) ARDS patients (68% vs 53.6%, p<0.001) and in MV patients (91.9% vs 77.7%, p<0.001), who required the prone position more frequently (74.8 vs 61%, p<0.001) and developed more infections. ICU and hospital mortality were increased in AKI patients (48.2% vs 17.7% and 51.1% vs 19%, p <0.001) respectively). AKI was an independent factor associated with mortality (IC 1.587-3.190). Mortality was higher in AKI patients who required RRT (55.8% vs 48.2%, p <0.04). Conclusions There is a high incidence of AKI in critically ill patients with COVID-19 disease and it is associated with higher mortality, increased organ failure, nosocomial infections and prolonged ICU stay.

The Role of Cell Cycle Arrest Biomarkers for Predicting Acute Kidney Injury in Critically Ill COVID-19 Patients: A Multicenter, Observational Study.

OBJECTIVES: Patients with COVID-19-associated acute respiratory distress syndrome (ARDS) have a high risk for developing acute kidney injury (AKI) which is associated with an increased risk of death and persistent renal failure. Early prediction of AKI is crucial in order to implement preventive strategies. The purpose of this study was to investigate the predictive performance of tissue inhibitor of metalloproteinases 2 and insulin like growth factor binding protein 7 (TIMP-2) × (IGFBP7) in critically ill patients with COVID-19-associated ARDS. DESIGN: Multicenter, prospective, observational study. SETTING: Twelve centers across Europe and United Kingdom. PATIENTS: Patients with moderate or severe COVID-19-associated ARDS were included and serial measurements of (TIMP-2) × (IGFBP7) were performed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the development of moderate or severe AKI according to the Kidney Disease: Improving Global Outcomes definition. Three hundred patients were available for the primary analysis, and 39 met the primary endpoint. At enrollment, urinary (TIMP-2) × (IGFBP7) had high predictive value for the primary endpoint with an area under the receiver operating characteristic curve of 0.89 (95% CI, 0.84-0.93). (TIMP-2) × (IGFBP7) was significantly higher in endpoint-positive patients at enrollment and at 12 hours. CONCLUSIONS: Urinary (TIMP-2) × (IGFBP7) predicts the occurrence of AKI in critically ill patients with COVID-19-associated ARDS.

Vitamin C deficiency in critically ill COVID-19 patients admitted to intensive care unit.

Objectives: To determine vitamin C plasma kinetics, through the measurement of vitamin C plasma concentrations, in critically ill Coronavirus infectious disease 2019 (COVID-19) patients, identifying eventually the onset of vitamin C deficiency. Design: Prospective, observational, single-center study. Setting: Intensive Care Unit (ICU), Vall d'Hebron University Hospital, Barcelona. Study period from November 12th, 2020, to February 24th, 2021. Patients: Patients who had a severe hypoxemic acute respiratory failure due to COVID-19 were included. Interventions: Plasma vitamin C concentrations were measured on days 1, 5, and 10 of ICU admission. There were no vitamin C enteral nor parenteral supplementation. The supportive treatment was performed following the standard of care or acute respiratory distress syndrome (ARDS) patients. Measurement: Plasma vitamin C concentrations were analyzed using an ultra-performance liquid chromatography (UPLC) system with a photodiode array detector (wavelength set to 245 nm). We categorized plasmatic levels of vitamin C as follows: undetectable: < 1,5 mg/L, deficiency: <2 mg/L. Low plasma concentrations: 2-5 mg/L; (normal plasma concentration: > 5 mg/L). Main results: Forty-three patients were included (65% men; mean age 62 ± 10 years). The median Sequential Organ Failure Assessment (SOFA) score was 3 (1-4), and the Acute Physiology and Chronic Health disease Classification System (APACHE II) score was 13 (10-22). Five patients had shock. Bacterial coinfection was documented in 7 patients (16%). Initially all patients required high-flow oxygen therapy, and 23 (53%) further needed invasive mechanical ventilation during 21 (± 10) days. The worst PaO2/FIO2 registered was 93 (± 29). ICU and hospital survival were 77 and 74%, respectively. Low or undetectable levels remained constant throughout the study period in the vast majority of patients. Conclusion: This observational study showed vitamin C plasma levels were undetectable on ICU admission in 86% of patients with acute respiratory failure due to COVID-19 pneumonia requiring respiratory support. This finding remained consistent throughout the study period.

Feasibility of a brief mindfulness-based program for burnout in pain healthcare professionals.

Introduction: Stress inherent to health care, which is characterized by work overload and shortage of specialized staff, is associated with decreased quality of life and suboptimal patient care. Mindfulness-based programs have proved to be effective in reducing stress in healthcare providers. This study aims to assess the feasibility of an 8-week mindfulness program to reduce the burnout levels of the staff of a pain clinic in a tertiary public hospital. Materials and methods: A longitudinal study with a within subject pre/post-intervention design, consisting of daily face-to-face 10-min sessions and the creation of a virtual group using a social media platform. Variables measured: burnout, mindfulness, empathy, self-compassion, and demographic characteristics. Results: Program feasibility (i.e., reach, adherence, acceptability, and preliminary effectiveness) was evaluated in 10 participants (6 physicians, 2 nurse practitioners, 1 nursing assistant, and 1 administrative). The results revealed a high reach (i.e., participation rate of 90%), excellent adherence to the program (daily practice 95% of times), and very good acceptability of the group format and satisfaction with most treatment components. Regarding potential effectiveness, we report the results of the Wilcoxon signed-rank tests and its associated effect size (r). We observed improvements in mindfulness and all its subscales (-2.077 ≤ Z ≤ -2.703, 0.69 ≤ r ≤ 0.90, all p < 0.05) except for non-reactivity and all subcomponents of self-compassion (-2.501 ≤ Z ≤ -2.611, 0.83 ≤ r ≤ 0.87, all p < 0.05) but not on its global self-compassion score. Empathy and burnout did not change. In an exploratory manner, however, we found significant reductions in the burnout component of emotional exhaustion, but only in physicians (Z = -2.201, p = 0.028, r = 0.73). Discussion: We believe that the 8-week mindfulness-based program described in the present investigation might be a feasible and potentially effective method that can be easily implemented to reduce burnout and promote mindfulness in specialized pain clinics.

Case report: Cytokine hemoadsorption in a case of hemophagocytic lymphohistiocytosis secondary to extranodal NK/T-cell lymphoma.

We discuss a single case of Hemophagocytic lymphohistiocytosis (HLH) due to NK-type non-Hodgkin lymphoma and Epstein-Barr virus reactivation with multiorgan dysfunction and distributive shock in which we performed cytokine hemoadsorption with Cytosorb ®. A full microbiological panel was carried out, including screening for imported disease, standard serologies and cultures for bacterial and fungal infection. A liver biopsy and bone marrow aspirate were performed, confirming the diagnosis. The patients fulfilled the HLH-2004 diagnostic criteria, and according to the 2018 Consensus Statements by the HLH Steering Committee of the Histiocyte Society, dexamethasone and etoposide were started. There was an associated hypercytokinemia and, due to refractory distributive shock, rescue therapy with cytokine hemoadsorption was performed during 24 h (within day 2 and 3 from ICU admission). After starting this procedure, rapid hemodynamic control was achieved with a significant reduction in vasopressor support requirements. This case report highlights that cytokine hemoadsorption can be an effective since rapid decrease in IL-10 levels and a significant hemodynamic improvement was achieved.

Impact of Early Mobilization Added to Respiratory Physiotherapy Postextubation on Weaning Success

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Precision medicine in sepsis and septic shock: From omics to clinical tools.

Sepsis is a heterogeneous disease with variable clinical course and several clinical phenotypes. As it is associated with an increased risk of death, patients with this condition are candidates for receipt of a very well-structured and protocolized treatment. All patients should receive the fundamental pillars of sepsis management, which are infection control, initial resuscitation, and multiorgan support. However, specific subgroups of patients may benefit from a personalized approach with interventions targeted towards specific pathophysiological mechanisms. Herein, we will review the framework for identifying subpopulations of patients with sepsis, septic shock, and multiorgan dysfunction who may benefit from specific therapies. Some of these approaches are still in the early stages of research, while others are already in routine use in clinical practice, but together will help in the effective generation and safe implementation of precision medicine in sepsis.

Endotoxin and Cytokine Sequential Hemoadsorption in Septic Shock and Multi-Organ Failure.

The mortality of septic shock remains high [Ann Intensive Care. 2017;7:19], so apart from usual therapy based on source control and antibiotics, some patients may need rescue therapies. Blood purification systems may play a role by facilitating the nonspecific removal of inflammatory mediators and microbiological toxins. There are different hemoadsorption systems, we describe in this case report the sequential use of Polymyxin B (PMX) endotoxin-adsorbing column (Toraymixin PMX-20R; Toray, Tokyo, Japan) and Cytosorb® (Cytosorbents Corp., New Jersey, USA).

Augmented renal clearance. An unnoticed relevant event.

Augmented renal clearance (ARC) is a phenomenon that can lead to a therapeutic failure of those drugs of renal clearance. The purpose of the study was to ascertain the prevalence of ARC in the critically ill patient, to study the glomerular filtration rate (GFR) throughout the follow-up and analyze the concordance between the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimation formula and measured GFR. Observational, prospective, multicenter study. ARC was defined as a creatinine clearance greater than 130 ml/min/1.73 m2. Eighteen hospitals were recruited. GFR measurements carried out twice weekly during a 2-month follow-up period. A total of 561 patients were included. ARC was found to have a non-negligible prevalence of 30%. More even, up to 10.7% already had ARC at intensive care unit (ICU) admission. No specific pattern of GFR was found during the follow-up. Patients in the ARC group were younger 56.5 (53.5-58.5) versus 66 (63.5-68.5) years than in the non-ARC group, p < 0.001. ICU mortality was lower in the ARC group, 6.9% versus 14.5%, p = 0.003. There was no concordance between the estimation of GFR by the CKD-EPI formula and GFR calculated from the 4-h urine. ARC is found in up to 30% of ICU patients, so renal removal drugs could be under dosed by up to 30%. And ARC is already detected on admission in 10%. It is a dynamic phenomenon without an established pattern that usually occurs in younger patients that can last for several weeks. And the CKD-EPI formula does not work to estimate the real creatinine clearance of these patients.

Hemadsorption as a Treatment Option for Multisystem Inflammatory Syndrome in Children Associated With COVID-19. A Case Report.

Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 is characterized by hypercytokinemia leading to overwhelming inflammation. We describe the use of a hemadsorption device as part of the supportive treatment for cytokine storm.

Cytokine Hemoadsorption as Rescue Therapy for Critically Ill Patients With SARS-CoV-2 Pneumonia With Severe Respiratory Failure and Hypercytokinemia.

Introduction: A dysregulated inflammatory response, known as "cytokine storm", plays an important role in the pathophysiology of coronavirus 2019 disease (COVID-19). Identifying patients with a dysregulated inflammatory response and at high risk for severe respiratory failure, organ dysfunction, and death is clinically relevant, as they could benefit from the specific therapies, such as cytokine removal by hemoadsorption. This study aimed to evaluate cytokine hemoadsorption as rescue therapy in critically ill patients with SARS-CoV-2 pneumonia, severe respiratory failure refractory to prone positioning, and hypercytokinemia. Methods: In this single center, observational and retrospective study, critically ill patients with SARS-CoV-2 pneumonia, severe acute respiratory failure, and hypercytokinemia were analyzed. All the patients underwent cytokine hemoadsorption using CytoSorb® (Cytosorbents Europe, Berlin, Germany). The indication for treatment was acute respiratory failure, inadequate clinical response to the prone position, and hypercytokinemia. Results: Among a total of 343 patients who were admitted to the intensive care unit (ICU) due to SARS-CoV-2 infection between March 3, 2020 and June 22, 2020, six patients received rescue therapy with cytokine hemoadsorption. All the patients needed invasive mechanical ventilation and prone positioning. A significant difference was found in the pre- and post-treatment D-dimer (17,868 mcg/ml [4,196-45,287] vs. 4,488 mcg/ml [3,166-17,076], p = 0.046), C-reactive protein (12.9 mg/dl [10.6] vs. 3.5 mg/dl [2.8], p = 0.028), ferritin (1,539 mcg/L [764-27,414] vs. 1,197 ng/ml [524-3,857], p = 0.04) and interleukin-6 (17,367 pg/ml [4,539-22,532] vs. 2,403 pg/ml [917-3,724], p = 0.043) levels. No significant differences in the pre- and post-treatment interleukin-10 levels (22.3 pg/ml [19.2-191] vs. 5.6 pg/ml [5.2-36.6], p = 0.068) were observed. Improvements in oxygenation (prehemoadsorption PaO2/FIO2 ratio 103 [18.4] vs. posthemoadsorption PaO2/FIO2 ratio 222 [20.9], p = 0.029) and in the organ dysfunction (prehemoadsorption SOFA score 9 [4.75] vs. posthemoadsorption SOFA score 7.7 [5.4], p = 0.046) were observed. ICU and in-hospital mortality was 33.7%. Conclusions: In this case series, critically ill patients with COVID-19 with severe acute respiratory failure refractory to prone positioning and hypercytokinemia who received adjuvant treatment with cytokine hemoadsorption showed a significant reduction in IL-6 plasma levels and other inflammatory biomarkers. Improvements in oxygenation and SOFA score were also observed.

Influenza infection in the intensive care unit: Four years after the 2009 pandemic / Infección por virus influenza en la unidad de cuidados intensivos: Cuatro años después de la pandemia del 2009

The role of influenza viruses in severe acute respiratory infection (SARI) in Intensive Care Units (ICU) remains unknown. The post-pandemic influenza A(H1N1)pdm09 period, in particular, has been poorly studied. OBJECTIVE: To identify influenza SARI patients in ICU, to assess the usefulness of the symptoms of influenza-like illness (ILI), and to compare the features of pandemic vs. post-pandemic influenza A(H1N1) pdm09 infection. METHODS: A prospective observational study with SARI patients admitted to ICU during the first three post-pandemic seasons. Patient demographics, characteristics and outcomes were recorded. An influenza epidemic period (IEP) was defined as >100 cases/100,000 inhabitants per week. RESULTS: One hundred sixty-three patients were diagnosed with SARI. ILI was present in 65 (39.9%) patients. Influenza infection was documented in 41 patients, 27 (41.5%) ILI patients, and 14 (14.3%) non-ILI patients, 27 of them during an IEP. Influenza A viruses were mainly responsible. Only five patients had influenza B virus infection, which were non-ILI during an IEP. SARI overall mortality was 22.1%, and 15% in influenza infection patients. Pandemic and post-pandemic influenza infection patients shared similar clinical features. CONCLUSIONS: During influenza epidemic periods, influenza infection screening should be considered in all SARI patients. Influenza SARI was mainly caused by subtype A(H1N1)pdm09 and A(H3N2) in post-pandemic seasons, and no differences were observed in ILI and mortality rate compared with a pandemic season

El papel de los virus influenza en la infección respiratoria aguda grave (IRAG) en Unidades de Cuidados Intensivos (UCI) sigue siendo desconocido. En particular, en el periodo post-pandemia de gripe A (H1N1) pdm09ha sido poco estudiada. OBJETIVO: identificar a los pacientes con IRAG por influenza en la UCI, para evaluar la utilidad de los síntomas por influenza (SI) y comparar las características de pandemia vs. post-pandemia de gripe A (H1N1) pdm09. MÉTODOS: Estudio observacional prospectivo de pacientes con IRAG admitidos en UCI durante las tres primeras temporadas post-pandémica. Se registraron demográficos, características y resultados de los pacientes. Período epidémico de Influenza (PEI) se definió por encima de 100 casos/100.000 habitantes por semana. RESULTADOS: Ciento sesenta y tres pacientes fueron diagnosticados con IRAG. SI estaba presente en 65 (39,9%). La infección por influenza se documentó en 41 pacientes, 27 (41,5%) pacientes SI y 14 (14,3%) de los pacientes que no presentaban SI; 27 de ellos durante el PEI. Los virus de influenza A fueron los principales responsables; sólo cinco pacientes presentaron infección por el virus de la influenza B, todos en PEI y sin SI. La mortalidad global fue del 22,1%, y 15% en pacientes con infección por gripe. Pacientes con infecciones de influenza pandémica y post-pandemia comparten características clínicas similares. CONCLUSIONES: Durante los períodos de epidemia de influenza, la detección de infecciones por influenza deben considerarse en todos los pacientes con IRAG. Influenza IRAG fue causado principalmente por el subtipo A (H1N1) pdm09 y A (H3N2) en las temporadas posteriores a la pandemia y no se observaron diferencias en la presentación de SI ni en la mortalidad en comparación con la pandemia

Influenza infection in the intensive care unit: Four years after the 2009 pandemic.

UNLABELLED: The role of influenza viruses in severe acute respiratory infection (SARI) in Intensive Care Units (ICU) remains unknown. The post-pandemic influenza A(H1N1)pdm09 period, in particular, has been poorly studied. OBJECTIVE: To identify influenza SARI patients in ICU, to assess the usefulness of the symptoms of influenza-like illness (ILI), and to compare the features of pandemic vs. post-pandemic influenza A(H1N1) pdm09 infection. METHODS: A prospective observational study with SARI patients admitted to ICU during the first three post-pandemic seasons. Patient demographics, characteristics and outcomes were recorded. An influenza epidemic period (IEP) was defined as >100 cases/100,000 inhabitants per week. RESULTS: One hundred sixty-three patients were diagnosed with SARI. ILI was present in 65 (39.9%) patients. Influenza infection was documented in 41 patients, 27 (41.5%) ILI patients, and 14 (14.3%) non-ILI patients, 27 of them during an IEP. Influenza A viruses were mainly responsible. Only five patients had influenza B virus infection, which were non-ILI during an IEP. SARI overall mortality was 22.1%, and 15% in influenza infection patients. Pandemic and post-pandemic influenza infection patients shared similar clinical features. CONCLUSIONS: During influenza epidemic periods, influenza infection screening should be considered in all SARI patients. Influenza SARI was mainly caused by subtype A(H1N1)pdm09 and A(H3N2) in post-pandemic seasons, and no differences were observed in ILI and mortality rate compared with a pandemic season.