In adults with post-COVID-19 conditions, a synbiotic preparation, SIM01, alleviated some symptoms at 6 mo.

SOURCE CITATION: Lau RI, Su Q, Lau IS, et al. A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2024;24:256-265. 38071990.

Sepsis outcomes in solid organ transplant recipients.

BACKGROUND: We present data on a cohort of patients diagnosed with sepsis over a 10-year period comparing outcomes in solid organ transplant (SOT) and non-solid organ transplant (non-SOT) recipients. METHODS: This is a retrospective single-center study of patients with diagnosis of sepsis from 1/1/06 to 6/30/16. Cases and controls were matched by year of sepsis diagnosis with propensity score matching. Conditional logistic regression and repeated measurement models were performed for binary outcomes. Trends over time for in-hospital mortality were determined using the Cochran-Armitage test. A gamma-distributed model was performed on the continuous variables. RESULTS: Overall, there were 18 632 admission encounters with a discharge diagnosis of sepsis in 14 780 unique patients. Of those admissions, 1689 were SOT recipients. After 1:1 matching by year, there were three thousand three hundred and forty patients (1670 cases; 1670 controls) diagnosed with sepsis. There was a decreasing trend for in-hospital mortality for sepsis over time in SOT patients and non-SOT patients (P < .05) due to early sepsis recognition and improved standard of care. Despite higher comorbidities in the SOT group, conditional logistic regression showed that in-hospital mortality for sepsis in SOT patients was similar compared with non-SOT patients (odds ratio [OR] =1.14 [95% confidence interval {CI}, 0.95-1.37], P = .161). However, heart and lung SOT subgroups had higher odds of dying compared with the non-SOT group (OR = 1.83 [95% CI, 1.30-2.57], P < .001 and OR = 1.77 [95% CI, 1.34-2.34], P < .001). On average, SOT patients had 2 days longer hospital length of stay compared with non-SOT admissions (17.00 ± 19.54 vs 15.23 ± 17.07, P < .05). Additionally, SOT patients had higher odds of hospital readmission within 30 days (OR = 1.25 [95% CI, 1.06-1.51], P = .020), and higher odds for DIC compared with non-SOT patients (OR = 1.76 [95% CI, 1.10-2.86], P = .021). CONCLUSION: Sepsis in solid organ transplants and non-solid organ transplant patients have similar mortality; however, the subset of heart and lung transplant recipients with sepsis has a higher rate of mortality compared with the non-solid organ transplant recipients. SOT with sepsis as a group has a higher hospital readmission rate compared with non-transplant sepsis patients.

Analysis of Rothman Index Data to Predict Postdischarge Adverse Events in a Medical Intensive Care Unit.

OBJECTIVE: Currently, there are no objective metrics included in the intensive care unit (ICU) discharge decision making process. In this study, we evaluate Rothman Index(RI) data for a possible metric as part of a quality improvement project. Our objectives were to determine whether RI could predict adverse events occurring within 72 hours of ICU discharge decision, the optimal clinical cutoff value for this metric, and to determine whether there is a relation between the RI warning alert 24 hours prior to discharge and adverse events postdischarge. DESIGN: Retrospective observational study. SETTING: Single center tertiary hospital. PATIENTS: Adult medical ICU patients discharged from the ICU between January 20, 2015 and March 14, 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 194 patients were studied with mean age of 62.74 (18.37) years. Data collection included RI at the time of decision-making for ICU discharge and the presence of any warning signals in the previous 24 hours. A 72-hour follow-up chart review recorded any adverse events, including readmission to a higher level of care, discontinuation of discharge due to clinical status change, emergency department visit if discharged home, rapid response activation, or cardiopulmonary arrest postdischarge. Adverse events after ICU discharge were observed in 31 (16%) patients with 9 events being ICU readmission (4.6%). Based on an age-adjusted multivariate model, a higher RI was associated with lower odds of an adverse event (odds ratio [OR] = 0.969, P = .006, confidence interval [CI]: 0.9487-0.9911). An RI value ≥ 50 was associated with 72% lower odds of an adverse event (OR = 0.2887, 95% CI = 0.1278-0.6517 and P = .003) compared to RI < 50. This RI cutoff value was associated with the largest decrease in odds of events. As expected, patients with a very high-risk warning alert had a higher proportion of adverse events compared to patients who did not. (31.75% vs 12.65%, P = < .02). CONCLUSIONS: Patients who have an RI < 50 or a very high-risk warning alert have a higher risk of adverse events postdischarge from the ICU. Rothman Index may be a useful metric for ICU discharge decision-making.

Clinical impact of pulmonary arterial hypertension on SARS-CoV-2 outcomes: U.S. pre-vaccination analysis.

Our retrospective study aimed to determine how pulmonary arterial hypertension (PAH) influences the clinical outcomes of COVID-19 admissions by using data from the 2020 nationwide inpatient sample (NIS). Among the 1,018,915 adults who were hospitalized with COVID-19 in 2020, 155 also had a PAH diagnosis. After adjusting for all baseline demographics and co-morbidities through multivariate analysis, we found that in patients admitted with a principal diagnosis of COVID-19, PAH was not associated with an increased risk of mortality compared to those without PAH. (adjusted OR 0.58 [95% CI 0.2-1.6] p=0.3). In addition, patients with both COVID-19 and PAH showed no statistically significant difference in the odds of requiring mechanical ventilation (adjusted OR 1.1 [95% CI 0.5-2.6] p=0.9), vasopressor needs (adjusted OR 0.4 [95% CI 0.1-3.5] p=0.4), acute kidney injury necessitating renal replacement therapy(adjusted OR 0.7 [95% CI 0.3-1.7] p=0.5), mean length of stay (LOS) (11.1 vs. 7.5 days), adjusted difference 3.1 [95% CI -3.8- 10.1] p=0.37) or mean total hospitalization charges ($195,815 vs $79,082, adjusted difference 107,146 [95% CI -93,939 - 308,232] p=0.29). Further studies are needed to investigate this subpopulation during the post-vaccination era to observe the effects of outcomes in these patients.

Clinical Outcomes of Heart Transplant Recipients Admitted with COVID-19 Infection in 2020: A Nationwide Analysis.

The COVID-19 pandemic, caused by infection of the SARS-CoV-2 virus, has impacted morbidity and mortality through widespread cytokine release and aberrant immunity; the mainstay of management has been immunosuppression. The aim of our retrospective study is to determine the effects of solid-organ transplantation (SOT) on COVID-19 admissions using data from the 2020 nationwide inpatient sample (NIS). After multivariate adjustment, we found COVID-19 admission with SOT had no difference in mortality (11.5% vs 11.1%, adjusted OR: 0.99 [95% CI 0.84-1.19, P = 0.99], no difference in need for vasopressor use (2.6% vs 1.8%, adjusted OR: 1.02 [95% CI 0.73-1.44, P = 0.88]), lower odds of requiring mechanical ventilation (MV) (13.7% vs 14.8%, adjusted OR: 0.83 [95% CI 0.71-0.97, P = 0.02]), lower odds of MV within 24 hours of admission (adjusted OR: 0.60 [95% CI 0.47-0.78, P < 0.01]), increased odds of mechanical circulatory support needs (adjusted OR 3.7 [95% CI 1.2-11.7, P = 0.025]), increased odds of acute renal failure requiring renal replacement therapy (adjusted OR 1.66 [95% CI 1.29-2.15, P < 0.01]), decreased mean length of stay (7.45 days vs 7.48 days, adjusted difference: 0.8 days less, P <0.01), and no difference in mean total hospitalization charges ($91,316 vs $79,100, adjusted difference: -$2,667, P = 0.57) compared to COVID-19 admissions without SOT.

A Time-Series Feature-Based Recursive Classification Model to Optimize Treatment Strategies for Improving Outcomes and Resource Allocations of COVID-19 Patients.

This paper presents a novel Lasso Logistic Regression model based on feature-based time series data to determine disease severity and when to administer drugs or escalate intervention procedures in patients with coronavirus disease 2019 (COVID-19). Advanced features were extracted from highly enriched and time series vital sign data of hospitalized COVID-19 patients, including oxygen saturation readings, and with a combination of patient demographic and comorbidity information, as inputs into the dynamic feature-based classification model. Such dynamic combinations brought deep insights to guide clinical decision-making of complex COVID-19 cases, including prognosis prediction, timing of drug administration, admission to intensive care units, and application of intervention procedures like ventilation and intubation. The COVID-19 patient classification model was developed utilizing 900 hospitalized COVID-19 patients in a leading multi-hospital system in Texas, United States. By providing mortality prediction based on time-series physiologic data, demographics, and clinical records of individual COVID-19 patients, the dynamic feature-based classification model can be used to improve efficacy of the COVID-19 patient treatment, prioritize medical resources, and reduce casualties. The uniqueness of our model is that it is based on just the first 24 hours of vital sign data such that clinical interventions can be decided early and applied effectively. Such a strategy could be extended to prioritize resource allocations and drug treatment for futurepandemic events.

Diffuse Cerebral Edema and Impending Herniation Complicating Hepatic Encephalopathy in Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disease characterized by the formation of cutaneous and visceral telangiectasias and arteriovenous malformations (AVM). Multiple organs may be affected, including the nasal mucosa, skin, lungs, gastrointestinal tract, and brain. The following case highlights a unique manifestation of HHT in a patient with a gastrointestinal hemorrhage and epistaxis, resulting in hyperammonemia and diffuse cerebral edema and herniation. Clinicians should be aware of this potential complication in such patients and initiate ammonia-reducing agents early to avoid this devastating consequence.

Use of radiolabeled hyaluronic acid for preclinical assessment of inflammatory injury and acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is accompanied by a dramatic increase in lung hyaluronic acid (HA), leading to a dose-dependent reduction of pulmonary oxygenation. This pattern is associated with severe infections, such as COVID-19, and other important lung injury etiologies. HA actively participates in molecular pathways involved in the cytokine storm of COVID-19-induced ARDS. The objective of this study was to evaluate an imaging approach of radiolabeled HA for assessment of dysregulated HA deposition in mouse models with skin inflammation and lipopolysaccharide (LPS)-induced ARDS using a novel portable intensified Quantum Imaging Detector (iQID) gamma camera system. METHODS: HA of 10 kDa molecular weight (HA10) was radiolabeled with 125I and 99mTc respectively to produce [125I]I-HA10 and [99mTc]Tc-HA10, followed by comparative studies on stability, in vivo biodistribution, and uptake at inflammatory skin sites in mice with 12-O-tetradecanoylphorbol-13-acetate (TPA)-inflamed ears. [99mTc]Tc-HA10 was used for iQID in vivo dynamic imaging of mice with ARDS induced by intratracheal instillation of LPS. RESULTS: [99mTc]Tc-HA10 and [125I]I-HA10 had similar biodistribution and localization at inflammatory sites. [99mTc]Tc-HA10 was shown to be feasible in measuring skin injury and monitoring skin wound healing. [99mTc]Tc-HA10 dynamic pulmonary images yielded good visualization of radioactive uptake in the lungs. There was significantly increased lung uptake and slower lung washout in mice with LPS-induced ARDS than in control mice. Postmortem biodistribution measurement of [99mTc]TcHA10 (%ID/g) was 11.0 ± 3.9 vs. 1.3 ± 0.3 in the ARDS mice (n = 6) and controls (n = 6) (P < 0.001), consistent with upregulated HA expression as determined by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) staining. CONCLUSIONS: [99mTc]Tc-HA10 is promising as a biomarker for evaluating HA dysregulation that contributes to pulmonary injury in ARDS. Rapid iQID imaging of [99mTc]Tc-HA10 clearance from injured lungs may provide a functional template for timely assessment and quantitative monitoring of pulmonary pathophysiology and intervention in ARDS.

Safety and Efficacy of Tocilizumab 4 or 8 mg/kg in Hospitalized Patients With Moderate to Severe Coronavirus Disease 2019 Pneumonia: A Randomized Clinical Trial.

BACKGROUND: Tocilizumab, an interleukin 6 receptor (IL-6R) antagonist monoclonal antibody, has shown efficacy in patients with coronavirus disease 2019 (COVID-19) pneumonia, but the optimal dose is unknown. METHODS: Patients hospitalized for moderate to severe COVID-19 pneumonia were randomized 1:1 to receive standard of care treatment and 1-2 doses of intravenous tocilizumab 4 mg/kg or 8 mg/kg (open-label). Primary pharmacokinetic and pharmacodynamic end points were serum concentrations of tocilizumab and soluble interleukin 6 receptor (sIL-6R), IL-6, ferritin, and C-reactive protein (CRP), from baseline to day 60. The secondary end point was safety. Key exploratory efficacy end points included clinical status, time to discharge, mortality rate, and incidence of mechanical ventilation. RESULTS: Of 100 patients randomized, 49 received tocilizumab 4 mg/kg and 48 received 8 mg/kg. In pharmacokinetic and sIL-6R assessments, dose-dependent differences were seen in patients who received 1 or 2 doses of 4 or 8 mg/kg. Serum concentrations of IL-6, ferritin, and CRP and safety outcomes were comparable between groups. Through day 60, serious adverse events were reported in 30.6% and 25.0% of patients in the 4- and 8-mg/kg groups, respectively. Eight patients (16.3%) in the 4-mg/kg group and 6 (12.5%) in the 8-mg/kg group died. Exploratory time-to-event outcomes favored 8 mg/kg within the first 2 weeks. CONCLUSIONS: In patients with moderate to severe COVID-19 pneumonia who received tocilizumab 4 or 8 mg/kg, pharmacokinetic and sIL-6R assessments showed expected dose-dependent effects; pharmacodynamic assessments and safety were comparable, with no new safety signals. Further study is required before a lower dose of tocilizumab can be recommended in patients with COVID-19 pneumonia. CLINICAL TRIALS REGISTRATION: NCT04363736.

New-Onset Seizures in Three COVID-19 Patients: A Case Series.

SUMMARY: Neurological manifestations of coronavirus disease 2019 most commonly present in severe cases and range from mild complications, such as headache and dizziness, to severe complications, such as encephalopathy and acute cerebrovascular disease. Seizures, however, are an underreported neurological manifestation of this disease. We present three critically ill coronavirus disease 2019 patients with EEG monitoring who developed new-onset seizures and encephalopathy up to three-and-a-half weeks after symptom onset. There are several speculated etiologies for the development of new-onset seizures; however, the pathogenic mechanism remains unknown. Testing of coronavirus disease 2019 in the cerebrospinal fluid in addition to extensive research on neurological manifestations is warranted.

A Year of Critical Care: The Changing Face of the ICU During COVID-19.

During the SARS-CoV-2 pandemic, admissions to hospital intensive care units (ICUs) surged, exerting unprecedented stress on ICU resources and operations. The novelty of the highly infectious coronavirus disease 2019 (COVID-19) required significant changes to the way critically ill patients were managed. Houston Methodist's incident command center team navigated this health crisis by ramping up its bed capacity, streamlining treatment algorithms, and optimizing ICU staffing while ensuring adequate supplies of personal protective equipment (PPE), ventilators, and other ICU essentials. A tele-critical-care program and its infrastructure were deployed to meet the demands of the pandemic. Community hospitals played a vital role in creating a collaborative ecosystem for the treatment and referral of critically ill patients. Overall, the healthcare industry's response to COVID-19 forced ICUs to become more efficient and dynamic, with improved patient safety and better resource utilization. This article provides an experiential account of Houston Methodist's response to the pandemic and discusses the resulting impact on the function of ICUs.

Clinical Outcomes Following Tocilizumab Administration in Mechanically Ventilated Coronavirus Disease 2019 Patients.

Effective treatments for the critically ill patient with novel coronavirus disease 2019 are desperately needed. Given the role of cytokine release syndrome in the pathogenesis of coronavirus disease 2019-associated respiratory distress, therapies aimed at mitigating cytokine release, such as the interleukin-6 receptor-inhibiting monoclonal antibody tocilizumab, represent potential treatment strategies. Therefore, we examined the outcomes of critically ill coronavirus disease 2019 patients treated with tocilizumab and factors associated with clinical improvement. DESIGN: A retrospective cohort analysis of 21-day outcomes for consecutive mechanically ventilated patients treated with tocilizumab from March 24, 2020, to May 4, 2020. SETTING: Nine ICUs at six hospitals within a hospital system in Houston, Texas, United States. PATIENTS: The first 62 coronavirus disease 2019 patients on invasive mechanical ventilation who were treated with tocilizumab, which was considered for all patients with severe disease. INTERVENTIONS: Tocilizumab was administered either at a weight-based dose of 4-8 mg/kg or at a flat dose of 400 mg, with repeat administration in some patients at the physician's discretion. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were mortality and clinical improvement, defined as extubation. By day 21 post-tocilizumab, clinical improvement occurred in 36 patients (58%) and 13 patients (21%) died. In both univariable and multivariable analyses, age less than 60 years was associated with clinical improvement. Transient transaminitis was the most common adverse reaction, occurring in 25 patients (40%). CONCLUSIONS: Based on clinical outcomes and mortality rates seen in previous reports of mechanically ventilated patients, tocilizumab, as part of the management strategy for severe coronavirus disease 2019, represents a promising option. These findings support the need for evaluation of tocilizumab in a randomized controlled trial.

Sepsis in a Panorama: What the Cardiovascular Physician Should Know.

Sepsis accounts for an estimated 30 million cases and 6 million deaths globally each year. According to a multidisciplinary task force convened by the Society of Critical Care Medicine and European Society of Intensive Care Medicine, sepsis is defined as life-threatening organ dysfunction due to a dysregulated host response to infection. Sepsis is a medical emergency, so much so that the World Health Organization made it a global health priority. Since patients with cardiovascular diseases have unique risk factors for sepsis, prompt and accurate diagnosis is critical. In this regard, the sepsis-specific Sequential Organ Failure Assessment (SOFA) helps clinicians identify the organ dysfunction and predict outcomes. Sepsis management is grouped into specific interventions called bundles, and completion of each bundle element is time sensitive. The U.S. Centers for Medicaid and Medicare Services and some state-specific regulations have made compliance with these bundles reportable as a quality measure. The updated Surviving Sepsis Campaign Hour-1 bundle recommends that lactate measurement, blood cultures procurement, broad spectrum antibiotics administration, resuscitation with 30 mL/kg crystalloid, and vasopressor initiation for hypotension all be initiated within 1 hour of time zero, which is from the time of triage in the emergency department or from sepsis diagnosis. Septic shock is defined as hypotension with a mean arterial pressure less than 65 mm Hg, requiring vasopressors despite adequate fluid resuscitation and/or lactic acid levels above 2 mmol/L. Both fluid resuscitation and clinical re-evaluation with lactate measurement guide the fluid and vasopressor therapy. Specific guidelines exist for organ support that address mechanical ventilation, blood transfusions, vasopressor choices, and nutrition.

Developing and testing a comprehensive tool to assess family meetings: Empirical distinctions between high- and low-quality meetings.

BACKGROUND: The heterogeneity with regard to findings on family meetings (or conferences) suggests a need to better understand factors that influence family meetings. While earlier studies have explored frequency or timing of family meetings, little is known about how factors (such as what is said during meetings, how it is said, and by whom) influence family meeting quality. OBJECTIVES: (1) To develop an evaluation tool to assess family meetings (Phase 1); (2) to identify factors that influence meeting quality by evaluating 34 family meetings (Phase 2). MATERIALS AND METHODS: For Phase 1, methods included developing a framework, cognitive testing, and finalizing the evaluation tool. The tool consisted of Facilitator Characteristics (i.e., gender, experience, and specialty of the person leading the meeting), and 22 items across 6 Meeting Elements (i.e., Introductions, Information Exchanges, Decisions, Closings, Communication Styles, and Emotional Support) and sub-elements. For Phase 2, methods included training evaluators, assessing family meetings, and analyzing data. We used Spearman's rank-order correlations to calculate meeting quality. Qualitative techniques were used to analyze free-text. RESULTS: No Facilitator Characteristic had a significant correlation with meeting quality. Sub-elements related to communication style and emotional support most strongly correlated with high-quality family meetings, as well as whether "next steps" were outlined (89.66%) and whether "family understanding" was elicited (86.21%). We also found a significant and strong positive association between overall proportion scores and evaluators' ratings (rs=0.731, p<0.001). CONCLUSIONS: We filled a gap by developing an evaluation tool to assess family meetings, and we identified how what is said during meetings impacts quality.