Impact of low dose inhaled nitric oxide treatment in spontaneously breathing and intubated COVID-19 patients: a retrospective propensity-matched study.

BACKGROUND: The benefit of Inhaled nitric oxide (iNO) therapy in the setting of COVID-19-related ARDS is obscure. We performed a multicenter retrospective study to evaluate the impact of iNO on patients with COVID-19 who require respiratory support. METHODS: This retrospective multicenter study included COVID-19 patients enrolled in the SCCM VIRUS COVID-19 registry who were admitted to different Mayo Clinic sites between March 2020 and June 2022 and required high-flow nasal cannula (HFNC), non-invasive ventilation (NIV), or invasive mechanical ventilation (IMV). Patients were included in the 'spontaneously breathing' group if they remained non-intubated or were initiated on an HFNC (± NIV) before intubation. Patients who got intubated without prior use of an HFNC (± NIV) were included in the 'intubated group.' They were further divided into categories based on their iNO usage. Propensity score matching (PSM) and inverse propensity of treatment weighting (IPTW) were performed to examine outcomes. RESULTS: Among 2767 patients included in our analysis, 1879 belonged to spontaneously breathing (153 received iNO), and 888 belonged to the intubated group (193 received iNO). There was a consistent improvement in FiO2 requirement, P/F ratio, and respiratory rate within 48 h of iNO use among both spontaneously breathing and intubated groups. However, there was no significant difference in intubation risk with iNO use among spontaneously breathing patients (PSM OR 1.08, CI 0.71-1.65; IPTW OR 1.10, CI 0.90-1.33). In a time-to-event analysis using Cox proportional hazard model, spontaneously breathing patients initiated on iNO had a lower hazard ratio of in-hospital mortality (PSM HR 0.49, CI 0.32-0.75, IPTW HR 0.40, 95% CI 0.26-0.62) but intubated patients did not (PSM HR: 0.90; CI 0.66-1.24, IPTW HR 0.98, 95% CI 0.73-1.31). iNO use was associated with longer in-hospital stays, ICU stays, ventilation duration, and a higher incidence of creatinine rise. CONCLUSIONS: This retrospective propensity-score matched study showed that spontaneously breathing COVID-19 patients on HFNC/ NIV support had a decreased in-hospital mortality risk with iNO use in a time-to-event analysis. Both intubated and spontaneously breathing patients had improvement in oxygenation parameters with iNO therapy but were associated with longer in-hospital stays, ICU stays, ventilation duration, and higher incidence of creatinine rise.

Veno-arteriovenous (V-AV) ECMO configuration: A single-center experience.

BACKGROUND: With increasing extracorporeal membrane oxygenation (ECMO) utilization over the last decade, clinicians have developed "hybrid" configurations to meet complex perfusion requirements. In the setting of differential hypoxemia, a veno-arteriovenous (V-AV) configuration provides oxygenated cardiac preload and hemodynamic support to satisfy physiologic demands. We aim to further characterize the patient population, indications, and outcomes associated with this hybrid configuration. METHODS: We retrospectively reviewed all adult patients placed on V-AV ECMO at our institution from June 2016 to December 2019. Through a review of the electronic medical records, data describing demographic features, comorbidities, and ECMO-specific information were analyzed systematically. RESULTS: 14 patients were placed on V-AV ECMO during the study period. Our cohort was 79% male with a median age of 54 and BMI of 30.3. These patients had a median SOFA-0 score of 15 and SAVE score of -12. Patients were treated with ECMO support for a median of 144.1 (IQR 98.5 - 183.1) hours, consisting of 0.2 (IQR 0 - 17.7) hours of VA and 92.4 (IQR 53.7 - 115.1) hours of V-AV followed by 67.4 (IQR 20.3 - 96.6) hours of VV support. Of these 14 patients, 11 survived to decannulation (79%) and 9 survived to hospital discharge (64%). CONCLUSION: ECMO patients with recovering left ventricular function and persistent gas exchange abnormalities are at risk for developing differential hypoxemia. We describe an approach to utilizing V-AV configuration when the likelihood of differential hypoxemia is extremely high, with a survival rate that compares favorably to Extracorporeal Life Support Organization statistics and published case series.

Outcomes of adult patients supported by extracorporeal membrane oxygenation (ECMO) following cardiopulmonary arrest. The Mayo Clinic experience.

INTRODUCTION: To describe our experience in use of extracorporeal life support (ECLS) as a rescue strategy in patients following cardiopulmonary resuscitation. METHODS: A retrospective analysis was performed for patients (n = 101) who received ECLS after cardiorespiratory arrest between May 2001 and December 2014. The primary outcome was survival to hospital discharge. RESULTS: In this cohort median (IQR) age was 56 (37-67) years, 53 (53%) were male, and 90 (89%) were Caucasian. Ventricular tachycardia or ventricular fibrillations were the initial cardiac rhythm in 49 (48.5%) and asystole/pulseless electrical activity in 37 (36.8%). Median (IQR) time to initiation of extracorporeal support from arrest time was 72 (43-170) min. The median (IQR) duration of support was 100 (47-157) hours. Renal failure (66%) and bleeding (66%) were the two most commonly observed complications during ECLS support. The survival to hospital discharge was seen in 47 (47%) patients, and good neurologic outcome (mRs 0-3) was seen in 29%. Acidosis, lactate and continuous renal replacement therapy were independent predictors of mortality. The median (IQR) intensive care unit stay was 14 (4-28) days and hospital stay was 17 (4-35) days. CONCLUSION: Our institutional experience with ECLS as a rescue measure following cardiac arrest is associated with improvement in mortality, and favorable neurologic status at hospital discharge.

Predictors of outpatient kidney function recovery among patients who initiate hemodialysis in the hospital.

BACKGROUND: Recent policy clarifications by the Centers for Medicare & Medicaid Services have changed access to outpatient dialysis care at end-stage renal disease (ESRD) facilities for individuals with acute kidney injury in the United States. Tools to predict "ESRD" and "acute" status in terms of kidney function recovery among patients who previously initiated dialysis therapy in the hospital could help inform patient management decisions. STUDY DESIGN: Historical cohort study. SETTING & PARTICIPANTS: Incident hemodialysis patients in the Mayo Clinic Health System who initiated in-hospital renal replacement therapy (RRT) and continued outpatient dialysis following hospital dismissal (2006 through 2009). PREDICTOR: Baseline estimated glomerular filtration rate (eGFR), acute tubular necrosis from sepsis or surgery, heart failure, intensive care unit, and dialysis access. OUTCOMES: Kidney function recovery defined as sufficient kidney function for outpatient hemodialysis therapy discontinuation. RESULTS: Cohort consisted of 281 patients with a mean age of 64 years, 63% men, 45% with heart failure, and baseline eGFR≥30mL/min/1.73m(2) in 46%. During a median of 8 months, 52 (19%) recovered, most (94%) within 6 months. Higher baseline eGFR (HR per 10-mL/min/1.73m(2) increase eGFR, 1.27; 95% CI, 1.16-1.39; P<0.001), acute tubular necrosis from sepsis or surgery (HR, 3.34; 95% CI, 1.83-6.24; P<0.001), and heart failure (HR, 0.40; 95% CI, 0.19-0.78, P=0.007) were independent predictors of recovery within 6 months, whereas first RRT in the intensive care unit and catheter dialysis access were not. There was a positive interaction between absence of heart failure and eGFR≥30mL/min/1.73m(2) for predicting kidney function recovery (P<0.001). LIMITATIONS: Sample size. CONCLUSIONS: Kidney function recovery in the outpatient hemodialysis unit following in-hospital RRT initiation is not rare. As expected, higher baseline eGFR is an important determinant of recovery. However, patients with heart failure are less likely to recover even with a higher baseline eGFR. Consideration of these factors at hospital discharge informs decisions on ESRD status designation and long-term hemodialysis care.

Incidence of Adverse Events during Continuous Renal Replacement Therapy.

BACKGROUND/AIMS: The incidence of adverse events (AEs) in adults who receive continuous renal replacement therapy (CRRT) is unknown. We report the incidence of mechanical, metabolic, and hemodynamic CRRT AEs. METHODS: This is a retrospective study of all consecutive adult patients (≥18 years) who underwent CRRT from January 1, 2007 to December 31, 2009. RESULTS: Out of 595 patients who underwent CRRT, 366 (62%) were male and 500 (84%) were Caucasian. Regional citrate anticoagulation was used in 98.6% of all patients. The most common clinically significant electrolyte derangements were ionized hypocalcemia (22%), ionized hypercalcemia (23%), and hyperphosphatemia (44%). Almost all (97%) patients had at least one additional AE including new onset hypotension (within the first hour after CRRT initiation) (43%), hypothermia (44%), new onset arrhythmias (29%), new onset anemia (31%) and thrombocytopenia (40%). CONCLUSIONS: ICU patients who require CRRT have a high incidence of AEs. Although the extent to which these complications are attributable to CRRT is not known, clinicians need to be cautious and aware of their high prevalence in this patient population.

Intravenous immunoglobulin in pediatrics: A review.

There has been a rapid expansion of the use of intravenous immunoglobulin (IVIG) for an ever-growing number of conditions. IVIG is used at a 'replacement dose' (400-600 mg/kg/month) in antibody deficiencies and is used at a high dose (2 g/kg) as an 'immunomodulatory' agent in an increasing number of immune and inflammatory disorders.(1) The limitations for IVIG are the cost of the preparation and the need for intravenous infusions. Due to the cost, shortages and growing use of IVIG there have been attempts to develop evidence-based guidelines for the use of IVIG in a wide variety of immune disorders in children and neonates. This commentary provides the recommendations and recent publication regarding the use of IVIG in various conditions in children.

Antibiotic Prophylaxis in Patients on Extracorporeal Membrane Oxygenation: A Systematic Review.

Despite the frequent use of prophylactic antibiotics in hospitals for extracorporeal membrane oxygenation (ECMO) patients, the Extracorporeal Life Support Organization (ELSO) Infectious Disease Task Force does not recommend routine antibiotic prophylaxis due to a lack of compelling evidence. We assessed the effectiveness of prophylactic antibiotics in ECMO patients. We conducted a comprehensive search of multiple databases from their inception up to September 6, 2023, on various databases using keywords like "antibiotics," "prophylaxis," "extracorporeal membrane oxygenation," and "ECMO." Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included research. We collected data using Microsoft Excel version 2016, mean and standard deviations were calculated for continuous data, while frequencies and percentages were calculated for binomial data. A total of three studies was included in the review with a total of 8,954 participants, of which 4,483 (50.06%) received antibiotic prophylaxis, and 1,131 (25.22%) were female. The administration of antibiotics prophylactically was associated with reduction in rate of mortality, the risk of infections, and complications like acute kidney injury and diarrhea. Although there have been some benefits on antibiotic prophylaxis, prospective research, and possibly the creation of tailored, ECMO-specific bundles will be needed to identify efficient ways to prevent ECMO infection.

Clinical Outcomes With Extracorporeal Membrane Oxygenation for Interstitial Lung Disease: Systematic Review and Meta-Analysis.

The evidence on indications, outcomes, and complications with the use of extracorporeal membrane oxygenation (ECMO) in the setting of interstitial lung disease (ILD) is limited in the existing literature. We performed a systematic review and meta-analysis for the use of ECMO in the setting of ILD to study the prognostic factors associated with in-hospital mortality. Eighteen unique studies with a total of 1,356 patients on ECMO for ILD were identified out of which 76.5% were on ECMO as a bridge to transplant (BTT) and the rest as a bridge to recovery (BTR). The overall in-hospital mortality was 45.76%, with 71.3% and 37.8% for BTR and BTT, respectively. Among the various prognostic factors, mortality was lower with younger age (mean difference = 3.15, 95% confidence interval [CI] = 0.82-5.49), use of awake veno-arterial (VA)-ECMO compared to veno-venous (VV)-ECMO (unadjusted odds ratio [OR] = 0.22, 95% CI = 0.13-0.37) in the overall cohort. In the setting of BTT, the use of VA-ECMO had a decreased hazard ratio (HR) compared to VV-ECMO (adjusted HR = 0.34, 95% CI = 0.15-0.81, p = 0.015). The findings of our meta-analysis are critical but are derived from retrospective studies with small sample sizes and thus are of low to very low-GRADE certainty.

Optimal planning and sizing of microgrid cluster for performance enhancement.

Access to electricity is a key indicator of a country's development. In developing nations like Ethiopia, this metric is particularly crucial for assessing progress. Currently, about 45.8% of Ethiopia's population lacks access to electricity, with rural areas experiencing even higher rates, reaching 57.2%. The Southern Nations, Nationalities, and People's (SNNP) region faces the greatest challenge, with 62.1% of its population lacking electricity. Ethiopia aims to achieve universal electricity access by 2030, and microgrid (MG) development is expected to play a pivotal role in meeting this goal. This study employs a multi-tier framework (MTF) to categorize village households based on electricity access, considering factors like income level and willingness to pay, to support the MG development process. Three villages-Toba, Koza, and Womba-in the SNNP region were selected for optimal MG sizing. Sensitivity variables such as global horizontal irradiance (GHI) variation, photovoltaic (PV) and battery prices, battery usage limits, and capacity shortage levels were analyzed for their impact on net present cost (NPC), initial capital cost, and cost of energy (COE) using HOMER Pro software. For example, in the Toba MG, increasing the capacity shortage from 0 to 10% reduced the COE from 0.1195 $/kWh to 0.09104 $/kWh, a 23.82% decrease. Additionally, fluctuations in PV and battery prices had a direct impact on the system's NPC. The study also explored the impact of clustering the microgrids by interconnecting the three individual systems and conducting a techno-economic analysis. The comparison between standalone MG operation and clustered microgrids revealed that, despite the added cost of interconnection, the benefits in terms of technological, economic, and reliable operation of the clustered system were comparable to standalone microgrids. Finally, a feasibility study was conducted for the potential grid extension of the Toba MG, which is located 130 km from the nearest substation in Sawla.

Epidemiology and molecular characterization of Mycobacterium tuberculosis including a drug-resistant strain associated with mortality of Asian elephants in Nepal 2019-2022.

Tuberculosis (TB) is an emerging threat to the survival of elephants in Nepal. We investigated the lung tissue samples from nine elephants that died from 2019 to 2022 in Nepal using culture, conventional PCR, and loop-mediated isothermal amplification (LAMP) and then performed genotyping of five PCR-positive isolates to understand the possible transmission dynamics of Mycobacterium tuberculosis (Mtb). Results showed that two-thirds (6/9) of elephants were confirmed to be infected from Mtb by LAMP, 5/9 by PCR, and 4/9 by culture. Genotyping of Mtb isolates showed that elephants were infected with the Indo-Oceanic and Beijing lineages including an isoniazid-resistant Beijing lineage. MIRU-VNTR-based phylogeny, gyrA, and katG sequencing showed the possibility of ongoing transmission of Indo-Oceanic lineages and likely transmission of the drug-resistant Beijing lineage from human to elephant. Implementation of comprehensive surveillance and preventive measures are urgently needed to address this zoonotic disease and protect elephants from TB in Nepal.

Assessing Right Ventricle Over Time in Patients on Veno-Venous Extracorporeal Membrane Oxygenation: Insights From Serial Echocardiography.

Extracorporeal membrane oxygenation (ECMO) is often used in acute respiratory distress syndrome (ARDS) with refractory hypoxemia. There is limited literature highlighting the development of right ventricular (RV) failure while on ECMO. We conducted a retrospective multicenter observational study including 70 patients who were placed on veno-venous (VV)-ECMO for respiratory failure at Mayo Clinic, Jacksonville, and Mayo Clinic, Rochester, between January 2018 and June 2022 and had at least two post-ECMO transthoracic echoes. The primary outcomes were the incidence and progression of RV dysfunction and dilatation. The secondary outcome was in-patient mortality. Among 70 patients in our cohort, 60.6% had a normal RV function at the time of ECMO placement, whereas only 42% had a normal RV function at the second post-ECMO echo. On multinomial regression, a moderate decrease in RV function was associated with ECMO flow (odds ratio [OR] = 2.32, p = 0.001) and ECMO duration (OR = 1.01, p = 0.01). A moderately dilated RV size was also associated with ECMO flow (OR = 2.62, p < 0.001) and ECMO duration (OR = 1.02, p = 0.02). An increasing degree of RV dysfunction was associated with worse outcomes. Our study showed that the increasing duration and flow of VV-ECMO correlated with progressive RV dilatation and dysfunction, which were associated with poor survival.

Association of estimated plasma volume with new onset acute kidney injury in hospitalized COVID-19 patients.

PURPOSE: To explore the association of estimated plasma volume (ePV) and plasma volume status (PVS) as surrogates of volume status with new-onset AKI and in-hospital mortality among hospitalized COVID-19 patients. MATERIALS AND METHODS: We performed a retrospective multi-center study on COVID-19-related ARDS patients who were admitted to the Mayo Clinic Enterprise health system. Plasma volume was calculated using the formulae for ePV and PVS, and longitudinal analysis was performed to find the association of ePV and PVS with new-onset AKI during hospitalization as the primary outcome and in-hospital mortality as a secondary outcome. RESULTS: Our analysis included 7616 COVID-19 patients with new-onset AKI occurring in 1365 (17.9%) and a mortality rate of 25.96% among them. A longitudinal multilevel multivariate analysis showed both ePV (OR 1.162; 95% CI 1.048-1.288, p=0.004) and PVS (OR 1.032; 95% CI 1.012-1.050, p=0.001) were independent predictors of new onset AKI. Higher PVS was independently associated with increased in-hospital mortality (OR 1.038, 95% CI 1.007-1.070, p=0.017), but not ePV (OR 0.868, 95% CI 0.740-1.018, p=0.082). CONCLUSION: A higher PVS correlated with a higher incidence of new-onset AKI and worse outcomes in our cohort of hospitalized COVID-19 patients. Further large-scale and prospective studies are needed to understand its utility.

Association of antibiotics with the outcomes in COVID-19 pneumonia patients with elevated PCT levels.

OBJECTIVE: To assess antibiotics impact on outcomes in COVID-19 pneumonia patients with varying procalcitonin (PCT) levels. METHODS: This retrospective cohort study included 3665 COVID-19 pneumonia patients hospitalized at five Mayo Clinic sites (March 2020 to June 2022). PCT levels were measured at admission. Patients' antibiotics use and outcomes were collected via the Society of Critical Care Medicine (SCCM) Viral Infection and Respiratory Illness Universal Study (VIRUS) registry. Patients were stratified into high and low PCT groups based on the first available PCT result. The distinction between high and low PCT was demarcated at both 0.25 ng/ml and 0.50 ng/ml. RESULTS: Our cohort consisted of 3665 patients admitted with COVID-19 pneumonia. The population was predominantly male, Caucasian and non-Hispanic. With the PCT cut-off of 0.25 ng/ml, 2375 (64.8 %) patients had a PCT level <0.25 ng/mL, and 1290 (35.2 %) had PCT ≥0.25 ng/ml. While when the PCT cut off of 0.50 ng/ml was used we observed 2934 (80.05 %) patients with a PCT <0.50 ng/ml while 731(19.94 %) patients had a PCT ≥0.50 ng/ml. Patients with higher PCT levels exhibited significantly higher rates of bacterial infections (0.25 ng/ml cut-off: 4.2 % vs 7.9 %; 0.50 ng/ml cut-off: 4.6 % vs 9.2 %). Antibiotics were used in 66.0 % of the cohort. Regardless of the PCT cutoffs, the antibiotics group showed increased hospital length of stay (LOS), intensive care unit (ICU) admission rate, and mortality. However, early de-escalation (<24 h) of antibiotics correlated with reduced hospital LOS, ICU LOS, and mortality. These results were consistent even after adjusting for confounders. CONCLUSION: Our study shows a substantial number of COVID-19 pneumonia patients received antibiotics despite a low incidence of bacterial infections. Therefore, antibiotics use in COVID pneumonia patients with PCT <0.5 in the absence of clinical evidence of bacterial infection has no beneficial effect.

Risk factors for hospitalization among older, incident haemodialysis patients.

AIMS: The number of elderly persons with end-stage renal disease is increasing with many requiring hospitalizations. This study examines the causes and predictors of hospitalization in older haemodialysis patients. METHODS: We reviewed hospitalizations of older (≥65 years) incident chronic haemodialysis patients initiating therapy between 1 January 2007 and 31 December 2009 under the care of a single Midwestern United States dialysis provider. RESULTS: Of 125 patients, the mean age was 76 ± 7 years and 72% were male. At first dialysis, 68% used a central venous catheter (CVC) and 51% were in the hospital. Mean follow-up was 1.8 ± 1.0 years. At least one hospitalization occurred in 89 (71%) patients and half of all patients were hospitalized once within the first 223 days. Total hospital admission rate was 1.48 per patient year with hospital days totalling 8.54 days per patient year. The three most common reasons for first admission were cardiac (33%), infection (18%) and gastrointestinal (12%). Predictors of future hospitalization included the first dialysis occurring in hospital (hazard ratios (HR) 2.1, 95% CI 1.4-3.3, P = 0.0005) and the use of a CVC at first haemodialysis (HR 2.6, CI 1.6-4.4, P < 0.0001). CONCLUSION: Hospitalizations are common in older incident haemodialysis patients. Access preparation and overall burden of illness leading to the initial hospitalization appear to play a role. Identification of additional factors associated with hospitalization will allow for focused interventions to reduce hospitalization rates and increase the value of care.

Acute Kidney Injury Management Strategies Peri-Cardiovascular Interventions.

In many countries, the aging population and the higher incidence of comorbid conditions have resulted in an ever-growing need for cardiac interventions. Acute kidney injury (AKI) is a common complication of these interventions, associated with higher mortalities, chronic or end-stage kidney disease, readmission rates, and hospital and post-discharge costs. The AKI pathophysiology includes contrast-associated AKI, hemodynamic changes, cardiorenal syndrome, and atheroembolism. Preventive measures include limiting contrast media dose, optimizing hemodynamic conditions, and limiting exposure to other nephrotoxins. This review article outlines the current state-of-art knowledge regarding AKI pathophysiology, risk factors, preventive measures, and management strategies in the peri-interventional period.

Liver Support Techniques in Acute and Hyperacute Liver Failure.

With the growing prevalence of acute liver failure or acute-on-chronic liver failure, on the one hand, and the limited supply of liver organs for transplantation, on the other hand, it is critical to the design, validate, and implement devices that can provide extracorporeal liver support (ECLS) as the bridge to transplantation or potentially destination therapies. The number of attempts to generate ECLS devices has resulted in several options with various levels of impact on clinical outcomes. The described ECLS tools could be as simple as devices used for kidney replacement therapies (e.g., continuous kidney replacement therapy) to tools that employ albumin (e.g., Prometheus, single-pass albumin dialysis, or molecular adsorbent recirculating system), fresh frozen plasma (e.g., high-volume plasmapheresis), or hepatocytes (e.g., extracorporeal liver assist device with hepatocytes) to support failing liver functions, that is, metabolic or synthetic functions. This chapter describes the current landscape of ECLS devices and their associated evidence-based data.

Percutaneous Transseptal Extracorporeal Membrane Oxygenation to Rescue a Failing Right Ventricle in an Animal Model.

OBJECTIVE: We tested the feasibility and effectiveness of a percutaneous atrial transseptal extracorporeal membrane oxygenation (ECMO) cannulation strategy in a right ventricular failure (RVF) model. METHODS: We performed 4 nonsurvival porcine experiments. Percutaneous transseptal access was achieved using a steerable introducer. For guidance, we used fluoroscopy, transesophageal echocardiogram (TEE), and intracardiac echocardiography (ICE). A ProtekDuo rapid deployment cannula (LivaNova, London, UK) was advanced across the septum into the left atrium by 2 to 3 cm. Pulmonary hypertension (PH) was induced by partially clamping the pulmonary artery. ECMO flow was cycled from high (2 to 3 L/min) to low (0.2 to 0.3 L/min) over 2 to 3 hours. RESULTS: Transseptal access using TEE and fluoroscopy was successful in 1 animal and unsuccessful in 1 animal. ICE provided optimal visualization for the remaining 2 animals. Mean arterial pressure (MAP) was associated immediately and consistently with high versus low ECMO flow rate (mean difference: 29 ± 3.1 mm Hg, P = 0.004) but was not restored to baseline values. RV pressure values were dynamic. Given time to equilibrate, mean RV pressure was restored to a baseline level. CONCLUSIONS: Percutaneous right atrium to left atrium transseptal cannulation relieved PH-RVF. MAP was restored to a viable level, and mean RV pressure was restored to a baseline level. Transseptal ECMO shows promise as a cannulation strategy to bridge patients with PH-RVF to lung transplant.

From numbers to medical knowledge: harnessing combinatorial data patterns to predict COVID-19 resource needs and distinguish patient subsets.

Background: The COVID-19 pandemic intensified the use of scarce resources, including extracorporeal membrane oxygenation (ECMO) and mechanical ventilation (MV). The combinatorial features of the immune system may be considered to estimate such needs and facilitate continuous open-ended knowledge discovery. Materials and methods: Computer-generated distinct data patterns derived from 283 white blood cell counts collected within five days after hospitalization from 97 COVID-19 patients were used to predict patient's use of hospital resources. Results: Alone, data on separate cell types-such as neutrophils-did not identify patients that required MV/ECMO. However, when structured as multicellular indicators, distinct data patterns displayed by such markers separated patients later needing or not needing MV/ECMO. Patients that eventually required MV/ECMO also revealed increased percentages of neutrophils and decreased percentages of lymphocytes on admission. Discussion/conclusion: Future use of limited hospital resources may be predicted when combinations of available blood leukocyte-related data are analyzed. New methods could also identify, upon admission, a subset of COVID-19 patients that reveal inflammation. Presented by individuals not previously exposed to MV/ECMO, this inflammation differs from the well-described inflammation induced after exposure to such resources. If shown to be reproducible in other clinical syndromes and populations, it is suggested that the analysis of immunological combinations may inform more and/or uncover novel information even in the absence of pre-established questions.

Association of plasma volume status with outcomes in hospitalized Covid-19 ARDS patients: A retrospective multicenter observational study.

PURPOSE: To evaluate the association of estimated plasma volume (ePV) and plasma volume status (PVS) on admission with the outcomes in COVID-19-related acute respiratory distress syndrome (ARDS) patients. MATERIALS AND METHODS: We performed a retrospective multi-center study on COVID-19-related ARDS patients who were admitted to the Mayo Clinic Enterprise health system. Plasma volume was calculated using the formulae for ePV and PVS, and these variables were analyzed for correlation with patient outcomes. RESULTS: Our analysis included 1298 patients with sequential organ failure assessment (SOFA) respiratory score ≥ 2 (PaO2/FIO2 ≤300 mmHg) and a mortality rate of 25.96%. A Cox proportional multivariate analysis showed PVS but not ePV as an independent correlation with 90-day mortality after adjusting for the covariates (HR: 1.015, 95% CI: 1.005-1.025, p = 0.002 and HR 1.054, 95% CI 0.958-1.159, p = 0.278 respectively). CONCLUSION: A lower PVS on admission correlated with a greater chance of survival in COVID-19-related ARDS patients. The role of PVS in guiding fluid management should be investigated in future prospective studies.

A retrospective analysis of normal saline and lactated ringers as resuscitation fluid in sepsis.

Background: The Surviving Sepsis Campaign suggested preferential resuscitation with balanced crystalloids, such as Lactated Ringer's (LR), although the level of recommendation was weak, and the quality of evidence was low. Past studies reported an association of unbalanced solutions, such as normal saline (NS), with increased AKI risks, metabolic acidosis, and prolonged ICU stay, although some of the findings are conflicting. We have compared the outcomes with the preferential use of normal saline vs. ringer's lactate in a cohort of sepsis patients. Method: We performed a retrospective cohort analysis of patients visiting the ED of 19 different Mayo Clinic sites between August 2018 to November 2020 with sepsis and receiving at least 30 mL/kg fluid in the first 6 h. Patients were divided into two cohorts based on the type of resuscitation fluid (LR vs. NS) and propensity-matching was done based on clinical characteristics as well as fluid amount (with 5 ml/kg). Single variable logistic regression (categorical outcomes) and Cox proportional hazards regression models were used to compare the primary and secondary outcomes between the 2 groups. Results: Out of 2022 patients meeting our inclusion criteria; 1,428 (70.6%) received NS, and 594 (29.4%) received LR as the predominant fluid (>30 mL/kg). Patients receiving predominantly NS were more likely to be male and older in age. The LR cohort had a higher BMI, lactate level and incidence of septic shock. Propensity-matched analysis did not show a difference in 30-day and in-hospital mortality rate, mechanical ventilation, oxygen therapy, or CRRT requirement. We did observe longer hospital LOS in the LR group (median 5 vs. 4 days, p = 0.047 and higher requirement for ICU post-admission (OR: 0.70; 95% CI: 0.51-0.96; p = 0.026) in the NS group. However, these did not remain statistically significant after adjustment for multiple testing. Conclusion: In our matched cohort, we did not show any statistically significant difference in mortality rates, hospital LOS, ICU admission after diagnosis, mechanical ventilation, oxygen therapy and RRT between sepsis patients receiving lactated ringers and normal saline as predominant resuscitation fluid. Further large-scale prospective studies are needed to solidify the current guidelines on the use of balanced crystalloids.