Development and Validation of a Policy Tree Approach for Optimizing Intravenous Fluids in Critically Ill Patients with Sepsis and Acute Kidney Injury.

Purpose: Intravenous fluids are mainstay of management of acute kidney injury (AKI) after sepsis but can cause fluid overload. Recent literature shows that restrictive fluid strategy may be beneficial in some patients with AKI, however, identifying these patients is challenging. We aimed to develop and validate a machine learning algorithm to identify patients who would benefit from a restrictive fluid strategy. Methods: We included patients with sepsis who developed AKI within 48 hours of ICU admission and defined restrictive fluid strategy as receiving <500mL fluids within 24 hours after AKI. Our primary outcome was early AKI reversal within 48 hours of AKI onset, and secondary outcomes included sustained AKI reversal and major adverse kidney events (MAKE) at discharge. We used a causal forest, a machine learning algorithm to estimate individual treatment effects and policy tree algorithm to identify patients who would benefit by restrictive fluid strategy. We developed the algorithm in MIMIC-IV and validated it in eICU database. Results: Among 2,091 patients in the external validation cohort, policy tree recommended restrictive fluids for 88.2%. Among these, patients who received restrictive fluids demonstrated significantly higher rate of early AKI reversal (48.2% vs 39.6%, p<0.001), sustained AKI reversal (36.7% vs 27.4%, p<0.001) and lower rates of MAKE by discharge (29.3% vs 35.1%, p=0.019). These results were consistent in adjusted analysis. Conclusion: Policy tree based on causal machine learning can identify septic patients with AKI who benefit from a restrictive fluid strategy. This approach needs to be validated in prospective trials. Take-home message: Intravenous fluids are the mainstay of management of acute kidney injury (AKI) after sepsis but can cause fluid overload. In this study using two large, distinct critical care databases, we developed and validated a causal machine learning based Policy Tree approach to identify septic patients with AKI who benefit from a restrictive fluid strategy, enhancing early and sustained AKI reversal, and reducing major adverse kidney events at discharge.

Autonomous precision resuscitation during ground and air transport of an animal hemorrhagic shock model.

We tested the ability of a physiologically driven minimally invasive closed-loop algorithm, called Resuscitation based on Functional Hemodynamic Monitoring (ReFit), to stabilize for up to 3 h a porcine model of noncompressible hemorrhage induced by severe liver injury and do so during both ground and air transport. Twelve animals were resuscitated using ReFit to drive fluid and vasopressor infusion to a mean arterial pressure (MAP) > 60 mmHg and heart rate < 110 min-1 30 min after MAP < 40 mmHg following liver injury. ReFit was initially validated in 8 animals in the laboratory, then in 4 animals during air (23nm and 35nm) and ground (9 mi) to air (9.5nm and 83m) transport returning to the laboratory. The ReFit algorithm kept all animals stable for ~ 3 h. Thus, ReFit algorithm can diagnose and treat ongoing hemorrhagic shock independent to the site of care or during transport. These results have implications for treatment of critically ill patients in remote, austere and contested environments and during transport to a higher level of care.

Hemoadsorption: Consensus report of the 30th Acute Disease Quality Initiative workgroup.

Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex-vivo, experimental, and clinical observations. Accordingly, unspecific adsorptive extracorporeal therapies have now been applied to the treatment of a wide array of conditions from poisoning to drug overdoses, to inflammatory states and sepsis, and acute or chronic liver and kidney failure. In response to the rapidly expanding knowledge base and increased clinical evidence, we convened an Acute Disease Quality Initiative (ADQI) consensus conference dedicated to such treatment. The data show that hemoadsorption has clinically acceptable short-term biocompatibility and safety, technical feasibility, and experimental demonstration of specified target molecule removal. Pilot studies demonstrate potentially beneficial effects on physiology and larger studies of endotoxin-based hemoadsorption have identified possible target phenotypes for larger randomized controlled trials (RCTs). Moreover, in a variety of endogenous and exogenous intoxications, removal of target molecules has been confirmed in vivo. However, some studies have raised concerns about harm or failed to deliver benefits. Thus, despite many achievements, modern hemoadsorption remains a novel and experimental intervention with limited data, and a large research agenda.

Metformin for sepsis-associated AKI: a protocol for the Randomized Clinical Trial of the Safety and FeasibiLity of Metformin as a Treatment for sepsis-associated AKI (LiMiT AKI).

INTRODUCTION: Acute kidney injury (AKI) is a common complication of sepsis associated with increased risk of death. Preclinical data and observational human studies suggest that activation of AMP-activated protein kinase, an ubiquitous master regulator of energy that can limit mitochondrial injury, with metformin may protect against sepsis-associated AKI (SA-AKI) and mortality. The Randomized Clinical Trial of the Safety and FeasibiLity of Metformin as a Treatment for sepsis-associated AKI (LiMiT AKI) aims to evaluate the safety and feasibility of enteral metformin in patients with sepsis at risk of developing SA-AKI. METHODS AND ANALYSIS: Blind, randomised, placebo-controlled clinical trial in a single-centre, quaternary teaching hospital in the USA. We will enrol adult patients (18 years of age or older) within 48 hours of meeting Sepsis-3 criteria, admitted to intensive care unit, with oral or enteral access. Patients will be randomised 1:1:1 to low-dose metformin (500 mg two times per day), high-dose metformin (1000 mg two times per day) or placebo for 5 days. Primary safety outcome will be the proportion of metformin-associated serious adverse events. Feasibility assessment will be based on acceptability by patients and clinicians, and by enrolment rate. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board. All patients or surrogates will provide written consent prior to enrolment and any study intervention. Metformin is a widely available, inexpensive medication with a long track record for safety, which if effective would be accessible and easy to deploy. We describe the study methods using the Standard Protocol Items for Randomized Trials framework and discuss key design features and methodological decisions. LiMiT AKI will investigate the feasibility and safety of metformin in critically ill patients with sepsis at risk of SA-AKI, in preparation for a future large-scale efficacy study. Main results will be published as soon as available after final analysis. TRIAL REGISTRATION NUMBER: NCT05900284.

Distribution of Acute and Chronic Kidney Disease Across Clinical Phenotypes for Sepsis.

BACKGROUND: Sepsis is the most common cause of acute kidney injury (AKI) in critically ill patients. Four phenotypes (α, ß, γ, δ) for sepsis, which have different outcomes and responses to treatment, were described using routine clinical data in the electronic health record. RESEARCH QUESTION: Do the frequencies of AKI, acute kidney disease (AKD), chronic kidney disease (CKD), and AKI on CKD differ by sepsis phenotype? STUDY DESIGN AND METHODS: This was a secondary analysis of a randomized clinical trial of early resuscitation, including patients with septic shock at 31 sites. After excluding patients with end-stage kidney disease and missing data, we determined frequencies of the following clinical outcomes: AKI (defined within 24 h as Kidney Disease: Improving Global Outcomes stages 2 or 3 or stage 1 with tissue inhibitor of metalloproteinases-2 × insulin-like growth factor binding protein 7 value of > 2.0), CKD, and AKD (persistence of AKI at any stage on day 7 after enrollment) across four phenotypes. We performed multivariable logistic regression to assess the risk-adjusted association between development of AKI and AKD and phenotype. RESULTS: Among 1,090 eligible patients, 543 patients (50%) had AKI. Across phenotypes, the frequencies of AKI varied, being highest in the δ and ß phenotypes (78% and 71%, respectively) and the lowest in the α phenotype (26%; P < .001). AKD occurred most often in the δ phenotype (41%) and least often in the α phenotype (8%; P < .001). The highest frequencies of CKD and of AKI on CKD were found in the ß phenotype (53% and 38% respectively; P < .001 for both). In the multivariable logistic regression models (α phenotype as reference), δ phenotype showed the strongest association with AKI (OR, 12.33; 95% CI, 7.81-19.47; P < .001) and AKD (OR, 9.18; 95% CI, 5.44-15.51; P < .001). INTERPRETATION: The rates of AKI and AKD differed across clinical sepsis phenotypes and are more common among patients with phenotypes ß and δ. Phenotype ß showed a higher level of underlying CKD that predisposed patients to new AKI. The α and γ phenotypes showed lower frequencies of AKI and less progression to AKD.

Improved waitlist and comparable post-transplant outcomes in simultaneous heart-kidney transplantation under the 2018 heart allocation system.

OBJECTIVE: This study aimed to investigate the clinical trends and the impact of the 2018 heart allocation policy change on both waitlist and post-transplant outcomes in simultaneous heart-kidney transplantation in the United States. METHODS: The United Network for Organ Sharing registry was queried to compare adult patients before and after the allocation policy change. This study included 2 separate analyses evaluating the waitlist and post-transplant outcomes. Multivariable analyses were performed to determine the 2018 allocation system's risk-adjusted hazards for 1-year waitlist and post-transplant mortality. RESULTS: The initial analysis investigating the waitlist outcomes included 1779 patients listed for simultaneous heart-kidney transplantation. Of these, 1075 patients (60.4%) were listed after the 2018 allocation policy change. After the policy change, the waitlist outcomes significantly improved with a shorter waitlist time, lower likelihood of de-listing, and higher likelihood of transplantation. In the subsequent analysis investigating the post-transplant outcomes, 1130 simultaneous heart-kidney transplant recipients were included, where 738 patients (65.3%) underwent simultaneous heart-kidney transplantation after the policy change. The 90-day, 6-month, and 1-year post-transplant survival and complication rates were comparable before and after the policy change. Multivariable analyses demonstrated that the 2018 allocation system positively impacted risk-adjusted 1-year waitlist mortality (sub-hazard ratio, 0.66, 95% CI, 0.51-0.85, P < .001), but it did not significantly impact risk-adjusted 1-year post-transplant mortality (hazard ratio, 1.03; 95% CI, 0.72-1.47, P = .876). CONCLUSIONS: This study demonstrates increased rates of simultaneous heart-kidney transplantation with a shorter waitlist time after the 2018 allocation policy change. Furthermore, there were improved waitlist outcomes and comparable early post-transplant survival after simultaneous heart-kidney transplantation under the 2018 allocation system.

A low total metabolic tumor volume independently predicts for a longer time to first treatment in initially observed, low tumor burden follicular lymphoma.

Watchful waiting is an acceptable management strategy for advanced-stage, low tumor burden (LTB) patients with follicular lymphoma (FL). However, the prediction of how long this treatment-free observation period will last remains imperfect. We explored whether total metabolic tumor volume (TMTV) and other positron emission tomography parameters were predictive of time to first treatment (TTFT). We analyzed 97 grade 1-3A advanced-stage LTB FL patients and found that a high TMTV was associated with other tumor burden features at diagnosis. Patients with a TMTV above our established cutoff of 50 mL had a significantly shorter median duration of observation (2.6 vs. 8.8 years; p = 0.001). At 5 years, 77% of patients with a high TMTV and 46% of patients with a low TMTV required treatment. In the multivariable analysis, a high TMTV was the only independent factor predicting TTFT (hazard ratio = 2.09; p = 0.017). Overall, TMTV is a strong predictor of the duration of observation in LTB FL patients. Upon validation of our cutoff in external series and standardization of the methodology, the TMTV could become an additional factor to consider deferring or initiating treatment in otherwise LTB patients.

Application of Cardiovascular Physiology to the Critically Ill Patient.

OBJECTIVES: To use the ventricular pressure-volume relationship and time-varying elastance model to provide a foundation for understanding cardiovascular physiology and pathophysiology, interpreting advanced hemodynamic monitoring, and for illustrating the physiologic basis and hemodynamic effects of therapeutic interventions. We will build on this foundation by using a cardiovascular simulator to illustrate the application of these principles in the care of patients with severe sepsis, cardiogenic shock, and acute mechanical circulatory support. DATA SOURCES: Publications relevant to the discussion of the time-varying elastance model, cardiogenic shock, and sepsis were retrieved from MEDLINE. Supporting evidence was also retrieved from MEDLINE when indicated. STUDY SELECTION, DATA EXTRACTION, AND SYNTHESIS: Data from relevant publications were reviewed and applied as indicated. CONCLUSIONS: The ventricular pressure-volume relationship and time-varying elastance model provide a foundation for understanding cardiovascular physiology and pathophysiology. We have built on this foundation by using a cardiovascular simulator to illustrate the application of these important principles and have demonstrated how complex pathophysiologic abnormalities alter clinical parameters used by the clinician at the bedside.

Feasibility Assessment of a Biomarker-Guided Kidney-Sparing Sepsis Bundle: The Limiting Acute Kidney Injury Progression In Sepsis Trial.

OBJECTIVES: To determine the feasibility, safety, and efficacy of a biomarker-guided implementation of a kidney-sparing sepsis bundle (KSSB) of care in comparison with standard of care (SOC) on clinical outcomes in patients with sepsis. DESIGN: Adaptive, multicenter, randomized clinical trial. SETTING: Five University Hospitals in Europe and North America. PATIENTS: Adult patients, admitted to the ICU with an indwelling urinary catheter and diagnosis of sepsis or septic shock, without acute kidney injury (acute kidney injury) stage 2 or 3 or chronic kidney disease. INTERVENTIONS: A three-level KSSB based on Kidney Disease: Improving Global Outcomes (KDIGOs) recommendations guided by serial measurements of urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 used as a combined biomarker [TIMP2]•[IGFBP7]. MEASUREMENTS AND MAIN RESULTS: The trial was stopped for low enrollment related to the COVID-19 pandemic. Nineteen patients enrolled in five sites over 12 months were randomized to the SOC (n = 8, 42.0%) or intervention (n = 11, 58.0%). The primary outcome was feasibility, and key secondary outcomes were safety and efficacy. Adherence to protocol in patients assigned to the first two levels of KSSB was 15 of 19 (81.8%) and 19 of 19 (100%) but was 1 of 4 (25%) for level 3 KSSB. Serious adverse events were more frequent in the intervention arm (4/11, 36.4%) than in the control arm (1/8, 12.5%), but none were related to study interventions. The secondary efficacy outcome was a composite of death, dialysis, or progression of greater than or equal to 2 stages of acute kidney injury within 72 hours after enrollment and was reached by 3 of 8 (37.5%) patients in the control arm, and 0 of 11 (0%) patients in the intervention arm. In the control arm, two patients experienced progression of acute kidney injury, and one patient died. CONCLUSIONS: Although the COVID-19 pandemic impeded recruitment, the actual implementation of a therapeutic strategy that deploys a KDIGO-based KSSB of care guided by risk stratification using urinary [TIMP2]•[IGFBP7] seems feasible and appears to be safe in patients with sepsis.

Germ line variants in patients with acute myeloid leukemia without a suspicion of hereditary hematologic malignancy syndrome.

Germ line predisposition in acute myeloid leukemia (AML) has gained attention in recent years because of a nonnegligible frequency and an impact on management of patients and their relatives. Risk alleles for AML development may be present in patients without a clinical suspicion of hereditary hematologic malignancy syndrome. In this study we investigated the presence of germ line variants (GVs) in 288 genes related to cancer predisposition in 47 patients with available paired, tumor-normal material, namely bone marrow stroma cells (n = 29), postremission bone marrow (n = 17), and saliva (n = 1). These patients correspond to 2 broad AML categories with heterogeneous genetic background (AML myelodysplasia related and AML defined by differentiation) and none of them had phenotypic abnormalities, previous history of cytopenia, or strong cancer aggregation. We found 11 pathogenic or likely pathogenic variants, 6 affecting genes related to autosomal dominant cancer predisposition syndromes (ATM, DDX41, and CHEK2) and 5 related to autosomal recessive bone marrow failure syndromes (FANCA, FANCM, SBDS, DNAJC21, and CSF3R). We did not find differences in clinical characteristics nor outcome between carriers of GVs vs noncarriers. Further studies in unselected AML cohorts are needed to determine GV incidence and penetrance and, in particular, to clarify the role of ATM nonsense mutations in AML predisposition.

Sepsis-associated acute kidney injury-treatment standard.

Sepsis is a host's deleterious response to infection, which could lead to life-threatening organ dysfunction. Sepsis-associated acute kidney injury (SA-AKI) is the most frequent organ dysfunction and is associated with increased morbidity and mortality. Sepsis contributes to ≈50% of all AKI in critically ill adult patients. A growing body of evidence has unveiled key aspects of the clinical risk factors, pathobiology, response to treatment and elements of renal recovery that have advanced our ability to detect, prevent and treat SA-AKI. Despite these advancements, SA-AKI remains a critical clinical condition and a major health burden, and further studies are needed to diminish the short and long-term consequences of SA-AKI. We review the current treatment standards and discuss novel developments in the pathophysiology, diagnosis, outcome prediction and management of SA-AKI.

Postoperative Acute Kidney Injury and Long-Term Outcomes After Lung Transplantation.

BACKGROUND: This study sought to characterize perioperative risk factors of acute kidney injury (AKI) and report outcomes associated with its development in the immediate postoperative setting after lung transplantation. METHODS: Study investigator performed a retrospective analysis of all adult patients undergoing primary lung transplantation at a single institution from January 1, 2011 to December 31, 2021 AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria after lung transplantation and was stratified on the basis of whether patients required renal replacement therapy (RRT; AKI-no RRT vs AKI-RRT). RESULTS: Of the 754 patients included, 369 (48.9%) any AKI developed in the postoperative period (252 AKI-no RRT vs 117 AKI-RRT). Risk factors for postoperative AKI included higher preoperative creatinine levels (odds ratio [OR], 5.15; P < .001), lower preoperative estimated glomerular filtration rate (OR, 0.99; P < 0.018), delayed chest closure (OR, 2.72; P < .001), and higher volumes of postoperative blood products (OR, 1.09; P < .001) in the multivariable analysis. On univariate analysis, both AKI groups were also associated with higher rates of pneumonia (P < .001), reintubation (P < .001), mortality on index admission (P < 0.001), longer ventilator duration (P < .001), longer intensive care unit length of stay (P < .001), and longer hospital length of stay (P < .001), with the highest rates in the AKI-RRT group. In a multivariable survival analysis, postoperative AKI-no RRT (hazard ratio [HR], 1.50; P = .006) and AKI-RRT (HR, 2.70; P < .001) were associated with significantly worse survival independent of severe grade 3 primary graft dysfunction at 72 hours (HR, 1.45; P = .038). CONCLUSIONS: The development of postoperative AKI was associated with numerous preoperative and intraoperative factors. Postoperative AKI remained significantly associated with poorer posttransplantation survival. Severe cases of AKI necessitating RRT portended the worst survival after lung transplantation.

Implementation of Nephroprotective Measures to Prevent Acute Kidney Injury in Septic Patients: A Retrospective Cohort Study.

BACKGROUND: Sepsis remains the leading cause of mortality in critically ill patients, and mortality is increased when acute kidney injury (AKI) occurs. The Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommends the implementation of supportive measures in patients at high risk for AKI. However, it remains unclear to what extent these nephroprotective measures are implemented in daily clinical practice in critically ill patients, especially those with high-risk exposures such as sepsis. METHODS: We analyzed the Medical Information Mart for Intensive Care IV (MIMIC-IV) database to identify septic patients with and without AKI. The primary outcome of interest was the adherence to the KDIGO bundle consisting of avoidance of nephrotoxic agents, implementation of a functional hemodynamic monitoring, optimization of perfusion pressure and volume status, close monitoring of renal function, avoidance of hyperglycemia, and avoidance of radiocontrast agents. Secondary outcomes included the development of AKI, progression of AKI, the use of renal replacement therapy (RRT), mortality, and a composite end point consisting of progression of AKI and mortality within 7 days. RESULTS: Our analysis included 34,679 patients with sepsis with 1.6% receiving the complete bundle (10% received 5, 42.3% 4, 35.4% 3, and 9.8% 2 bundle components). In 56.4%, nephrotoxic agents were avoided, and hemodynamic optimization was reached in 86.5%. Secondary end points were improved in patients with bundle adherence. Avoidance of nephrotoxic drugs and optimization of hemodynamics were significantly associated with lower rates of AKI and improved patient outcomes, including 30-day mortality. CONCLUSIONS: Implementation of the KDIGO bundle is poor in patients with sepsis but may be associated with improved outcomes.

Sepsis-associated acute kidney injury: consensus report of the 28th Acute Disease Quality Initiative workgroup.

Sepsis-associated acute kidney injury (SA-AKI) is common in critically ill patients and is strongly associated with adverse outcomes, including an increased risk of chronic kidney disease, cardiovascular events and death. The pathophysiology of SA-AKI remains elusive, although microcirculatory dysfunction, cellular metabolic reprogramming and dysregulated inflammatory responses have been implicated in preclinical studies. SA-AKI is best defined as the occurrence of AKI within 7 days of sepsis onset (diagnosed according to Kidney Disease Improving Global Outcome criteria and Sepsis 3 criteria, respectively). Improving outcomes in SA-AKI is challenging, as patients can present with either clinical or subclinical AKI. Early identification of patients at risk of AKI, or at risk of progressing to severe and/or persistent AKI, is crucial to the timely initiation of adequate supportive measures, including limiting further insults to the kidney. Accordingly, the discovery of biomarkers associated with AKI that can aid in early diagnosis is an area of intensive investigation. Additionally, high-quality evidence on best-practice care of patients with AKI, sepsis and SA-AKI has continued to accrue. Although specific therapeutic options are limited, several clinical trials have evaluated the use of care bundles and extracorporeal techniques as potential therapeutic approaches. Here we provide graded recommendations for managing SA-AKI and highlight priorities for future research.

Herpes simplex virus type 1 (HSV-1) over-infection in patients with acute respiratory distress syndrome secondary to COVID-19 pneumonia: Impact on mortality.

Objective: Herpes simplex virus type 1 (HSV-1) reactivation have been described in patients with invasive mechanical ventilation and recently in patients with acute respiratory distress syndrome (ARDS) secondary to COVID-19 with higher rates of reactivation than were detected previously in critical care, and although the diagnosis of HSV-1 pneumonia is not easy, its presence is associate with an increase in morbidity and mortality. The objective of this study is to determinate if the identification of HSV-1 in lower airway of patients with ARDS secondary to COVID-19 have influence in clinical outcome and mortality. Method: Two hundred twenty-four admitted patients in intensive care unit (ICU) of Complejo Hospitalario Universitario de Toledo diagnosed of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were reviewed and were selected those with mechanical ventilation who had undergone (BAL). It was registered all results of HSV-1 PCR (negative and positive). Results: During the study period (November 28, 2020 to April 13, 2021) was admitted 224 patients in ICU diagnosed of SARS-CoV-2 pneumonia. Eighty-three patients of them had undergone BAL, with HSV-1 PCR positive result in 47 (56%), and negative result in 36 (43.4%). We performed pathological anatomy study in BAL samples on 26 of the total BAL realized. Typical cytopathic characteristics of HSV-1 were found in 13 samples (50%) and 11 of them (84.6%) have had HSV-1 PCR positive result. Thirty days mortality was significantly higher in the group of patients with HSV-1 PCR positive result (33.5% vs. 57.4%, p = 0.015). This difference was stronger in the group of patients with HSV-1 findings in the pathological anatomy study (30.8% vs. 69.2%, p = 0.047). Conclusion: Our results suggest that ARDS secondary to SARS-CoV-2 pneumonia is highly associated to HSV-1 reactivation and that the finding of HSV-1 in lower airway is associated with a worst prognostic and with significantly mortality increase. It is necessary to carry out more extensive studies to determinate if treatment with acyclovir can improve the prognosis of these patients.

Objetivo: Las reactivaciones del virus herpes simple (VHS) están descritas en los pacientes en ventilación mecánica invasiva y recientemente en el síndrome de distrés respiratorio agudo (SDRA) por COVID-19, con tasas más altas que las descritas previamente en pacientes críticos, y aunque el diagnóstico de neumonía por VHS es difícil, su presencia se asocia con aumento de la morbimortalidad. El objetivo de este estudio es determinar si la identificación de VHS en el tracto respiratorio inferior en pacientes en ventilación mecánica con SDRA por COVID-19 influye sobre la evolución clínica y la mortalidad. Método: Se revisaron 224 pacientes ingresados en el servicio de medicina intensiva del Complejo Hospitalario de Toledo con el diagnóstico de neumonía por SARS-CoV-2 y se seleccionaron los pacientes en ventilación mecánica a los que se les había realizado lavado broncoalveolar (LBA). Se registraron todos los resultados de la PCR, tanto si fue positiva como si fue negativa para VHS. Resultados: Durante el periodo de estudio (del 28 de noviembre de 2020 hasta el 13 de abril de 2021) ingresaron 224 pacientes en la UCI con el diagnóstico de neumonía por SARS-CoV-2. De ellos, en 83 se realizó lavado broncoalveolar (LBA), siendo la PCR para VHS-1 positiva en 47 y negativa en 36 (56,6%). Realizamos estudio anatomopatológico en muestras de LBA a 26 pacientes del total de la muestra. Se encontraron características citopáticas típicas de infección por herpes en 13 (50%), de los cuales 11 (84,6%) tenían PCR positiva. La mortalidad a los 30 días fue significativamente mayor en el grupo de pacientes con PCR positiva (33,5% vs 57,4%, p = 0,015). Esta diferencia fue aún más marcada en el grupo con hallazgos anatomopatológicos compatibles con neumonía por VHS (30,8% versus 69,2%, p = 0,047). Conclusión: Nuestros resultados sugieren que el SDRA secundario a neumonía por SARS-CoV-2 se asocia a una alta reactivación del VHS y que su hallazgo en el tracto respiratorio inferior se asocia con un peor pronóstico y un aumento significativo de la mortalidad. Son necesarios estudios más amplios para determinar si el tratamiento con aciclovir puede mejorar el pronóstico de estos pacientes.

Incidence, risk factors, and impact of early cardiac toxicity after allogeneic hematopoietic cell transplant.

This study investigates early cardiac events (ECEs) occurring during the first 180 days after allogeneic hematopoietic cell transplant (allo-HCT) in 416 adults receiving posttransplant cyclophosphamide (PTCY) (n = 258) or not receiving PTCY (n = 158). Total body irradiation (TBI) was given to 133 (31.9%) patients, of whom 111 (83.4%) received TBI combined with PTCY. The day +180 cumulative incidence function (CIF) of ECEs was 8.4%, with heart failure (n = 13) and pericardial complications (n = 11) being the most prevalent complications. The incidence of ECEs was higher in patients receiving PTCY, and receiving TBI. ECEs were more prevalent in haploidentical HCTs than in matched sibling donor, 10/10 HLA-matched unrelated donor, and 9/10 HLA-mismatched unrelated donor allo-HCTs. As for the ECE risk from the combination of PTCY and TBI, the multivariate analysis reported that patients receiving PTCY without TBI, TBI without PTCY, and TBI with PTCY were at higher risk for ECEs compared with patients receiving neither PTCY nor TBI. Pre-existing cardiac morbidity predicted ECEs. However, using high-dose CY-containing preparative regimens did not increase the risk for cardiac toxicity at +180 days after allo-HCT. ECEs were associated with higher nonrelapse mortality and lower overall survival. Considering that PTCY and TBI were predictors for ECEs, and the impact of this complication on transplant mortality, the implementation of cardiac monitoring plans could be appropriate in patients receiving these medications.

SEVERE CORONAVIRUS DISEASE 2019: FROM PATHOGENESIS TO THERAPY.

ABSTRACT: The COVID-19 pandemic has been a challenge to propose efficient therapies. Because severe SARS-CoV2 infection is a viral sepsis eventually followed by an immunological autoinflammatory phenomenon, many approaches have been inspired by the previous attempts made in bacterial sepsis, while specific antiviral strategies (use of interferon or specific drugs) have been additionally investigated. We summarize our current thinking on the use of SARS-CoV-2 antivirals, corticosteroids, anti-IL-1, anti-IL-6, anti-C5a, as well as stem cell therapy in severe COVID-19. Patient stratification and appropriate time window will be important to be defined to guide successful treatment.