Intensive Care Unit Status Research Articles

Risk factors for mid- and long-term mortality in lung transplant recipients aged 70 years and older.

With increased lung transplantation in those aged 70 and older, limited literature addresses risk factors affecting their survival. Our study aims to identify independent factors impacting mid- and long-term mortality in this elderly population. This study analyzed lung transplant patients over 70 from May 2005 to December 2022 using United Network for Organ Sharing data. The 3- or 5-year cohort excluded multi-organ, secondary transplantation and loss to follow-up. Univariable Cox analysis was conducted to assess recipient, donor and transplant factors. Factors with a significance level of P < 0.2 were subsequently included in a multivariable Cox model to identify correlations with 3- and 5-year mortality in patients aged over 70. Multivariable analysis has identified key factors affecting 3- and 5-year mortality in elderly lung transplant patients over 70. Common notable factors include recipient total bilirubin, intensive care unit status at the time of transplantation, donor diabetes, Cytomegalovirus(CMV) mismatch and single lung transplantation. Additionally, Hispanic/Latino patients and ischaemia time of the transplant significantly impact the 3-year mortality, while recipient age, diabetes, nitric oxide use before transplantation and creatinine were identified as unique independent risk factors affecting the 5-year morality. The study identified several independent risk factors that impact the mid- and long-term survival of lung transplantation for individuals over 70 years. These findings can contribute to the optimization of lung transplant treatment strategies and perioperative management in elderly patients, thereby enhancing the survival rate of this age group.

Relation between nutritional status on clinical outcomes of critically ill patients: emphasizing nutritional screening tools in a prospective cohort investigation

BackgroundMalnutrition is a significant concern reported in adult critically ill patients, yet there is no gold standard to assess nutritional status in this population. This study examines the association between nutritional status and clinical outcomes in intensive care unit (ICU) patients using nutritional risk assessment tools and aims to look for the best tool.MethodIn a single-center prospective cohort study among 165 patients, the predictive performance of high or low malnutrition risk assessed by Nutritional Risk Screening (NRS), Modified Nutrition Risk in Critically Ill (m-NUTRIC), Mini-Nutritional-Assessment Short-Form (MNA-SF), Controlling Nutritional status (CONUT), and Prognostic Nutritional Index (PNI) were evaluated and compared for mortality, organ failure, length of hospitalization, and mechanical ventilation (MV).ResultsDifferent assessment tools showed various nutritional statuses. m-NUTRIC and NRS-2002 were found to be associated more strongly relative to other tools with mortality (RR = 1.72; 95% CI, 1.42–2.08) and (RR = 1.37; 95% CI, 1.08–1.72), organ failure (RR = 1.69; 95% CI, 1.44–1.96) and (RR = 1.22; 95% CI, 0.99–1.48), MV (RR = 1.46; 95% CI, 1.27–1.65) and (RR = 1.21; 95% CI, 1.04–1.39) respectively. There was no correlation between malnutrition levels assessed by mentioned tools except for NRS-2002 and length of hospitalization. In predicting mortality or illness severity, the cut points were different for some tools like NUTRIC-score and all assessed outcomes (3.5), MNA-SF and mortality (6.5), CONUT with mortality, and MV (6.5).ConclusionsA considerable proportion of patients admitted to the ICU are at high risk for malnutrition. Compared to other tools, m-NUTRIC and NRS-2002 proved superior in predicting clinical outcomes in critically ill patients. Other tools overestimated the risk of malnutrition in the ICU so couldn’t predict clinical outcomes correctly.

Increased mortality in infants with abnormal T-cell receptor excision circles.

T-Cell Receptor Excision Circles based newborn screening (TREC-NBS) allows for early detection of T-cell lymphopenia in infants with primary immunodeficiency disorders (PIDD). The utility of abnormal TREC-NBS in infants without PIDD is not well studied. We sought to evaluate the association of abnormal TREC-NBS with mortality. 365,207 TREC-NBS from October 2011 to December 2014 were reviewed. 467 newborns had abnormal screens and did not meet the criteria for a PIDD diagnosis. Cases were matched to controls (1:3) based on gestational age, birth weight, neonatal intensive care unit status (NICU), and race. Data were obtained through NBS, birth and death certificates records from the Michigan Department of Health and Human Services (MDHHS) databases. Infants with abnormal TREC-NBS had higher mortality even when PIDD was ruled-out. Transient abnormal TREC-NBS was not associated with higher mortality, but unresolved or late abnormal TREC-NBS was associated with higher mortality. Infants with late abnormal TREC-NBS had severe prematurity, lower birth weight, lower Apgar scores, and higher percentage of congenital anomalies. Infants with abnormal TREC-NBS may be at a higher risk of morbidity and mortality and should be carefully followed, especially if discharged home before a repeat screen can be completed. This study explores the risk factors and mortality for newborns with secondary T-cell lymphopenia captured on T-Cell Receptor Excision Circles based newborn screening (TREC-NBS). Abnormal TREC-NBS allows for prompt life-saving interventions for primary immunological conditions such as Severe Combined Immunodeficiency (SCID), but can also be associated with non-immunologic conditions. Unresolved and late abnormal TREC-NBS is associated with higher mortality even without primary immunodeficiency, likely detected in infants with more severe prematurity, lower birth weight, and congenital anomalies. TREC-NBS positive infants with secondary T-cell lymphopenia require special attention and close monitoring.

The diagnostic yield of a 2-h versus a 30-min electroencephalogram for patients with altered mental status in neurological intensive care unit

BackgroundThe continuous electroencephalogram (cEEG) monitoring is recommended for critical ill patients with altered mental status, The cEEG detects seizure activity and nonconvulsive status epilepticus (NCSE) more efficiently than routine electroencephalogram (rEEG). Yet, cEEG is not widely available in many neurological intensive care units (NICU) in limited resource countries. Ideal study duration, and whether cEEG is useful and cost-effective in terms of patient outcome compared to (rEEG), is still questions under research. The main objective in our study was the relative diagnostic yield of the 2 h, prolonged EEG recording, compared to the 30-min rEEG recording in the NICU.ResultsThere was no significant diagnostic yield for the 2-h electroencephalogram (EEG) over the 30-min EEG for patient with altered mental status in the NICU. Being with altered mental state in an NICU carries a poor outcome, we found that death occurred in 68.9% of patients. Acute ischemic stroke is the most common cause of altered mental status in NICU by about 53.3% of patients. Less than half of the patients (42.2%) were receiving anti-seizure medications (ASM).ConclusionsAs long as the cEEG is not available in the NICU, the 30-min EEG has a good diagnostic yield and it is almost equivalent to the prolonged 2-h EEG, and if the EEG is recommended for a longer duration, we recommend a long-term EEG more than 2 h.

The impact of implementation of rapid blood culture identification panels on antimicrobial optimization: a retrospective cohort study.

Determine the impact of limited implementation of a rapid blood culture identification (BCID) panel. Retrospective cohort study. From February to April 2022, positive blood cultures identified via e-Plex BCID (Roche, Carlsbad, CA) were compared to those identified using standard microbial identification techniques. The primary outcomes assessed were time to optimal therapy, time to de-escalation of anti-MRSA (methicillin-resistant Staphylococcus aureus) agents, and time to de-escalation of anti-pseudomonal agents. Additional analysis investigated the impact of the availability of antimicrobial stewardship program support. This study was conducted at Grady Health System, a large metropolitan safety-net hospital in the southeastern United States. A total of 253 blood cultures were included in this study (153 BCID and 100 standard). Blood culture identification use was associated with a reduction in median time to optimal antimicrobial therapy (43.4 vs 72.1 h, P < .001) and median time to de-escalation of anti-MRSA agents (27.7 vs 46.7 h, P = .006), and a trend towards reduction of median time to de-escalation of anti-pseudomonal agents (38.8 vs 54.8 h, P = .07). These reductions persisted when controlling for patient age, sex, intensive care unit status, Charlson Comorbidity Index, and antimicrobial stewardship program availability. Despite restricted use and lack of 24/7 antimicrobial stewardship program availability, BCID panel utilization was associated with earlier initiation of optimal therapy and pathogen identification with subsequent de-escalation of broad-spectrum antimicrobials, as compared to standard antimicrobial techniques. This suggests the potential for benefit from adopting novel diagnostic technologies outside of idealized fully-resourced settings.

Nutrition status in neuro trauma intensive care units- A cross sectional descriptive study

Nutrition status in neuro trauma intensive care units- A cross sectional descriptive study

Predictors of inpatient outcomes of COVID-19 infection in patients with cirrhosis in the early pandemic phase: A nationwide survey.

Previous studies conducted at single centers have suggested that patients with cirrhosis are at a greater risk for worse outcomes with COVID-19. However, there is limited data on a national level in the United States. We aimed to study hospital-related outcomes and identify the predictors of poor outcomes in patients with cirrhosis and concurrent COVID-19. We queried 2020 National Inpatient and Readmission databases to identify all hospitalizations due to cirrhosis in adults with a diagnosis of COVID-19. Primary outcomes included inpatient mortality, mechanical ventilation (MV), and intensive care unit (ICU) utilization. Secondary outcomes included mean length of stay (LOS) and mean hospitalization costs. We classified cirrhosis into compensated (CC) and decompensated (DC) groups. We identified 25194 hospitalizations of adult patients due to cirrhosis with a concurrent diagnosis of COVID-19. These patients had higher mortality (19.50% vs 6.19%, P ≤ 0.01), MV (11.7% vs 2.8%, P ≤ 0.01), ICU utilization (17.3% vs 8.1%, P ≤ 0.01), LOS (8.89 days vs 6.16 days, P ≤ 0.01), and total hospitalization costs ($24 817 vs $18 505, P ≤ 0.01) than those without COVID-19. On subgroup analysis, patients in the DC group had higher mortality, LOS, and hospitalization costs compared to those in the CC group. On multivariate analysis, we also found that COVID-19 infection, age, Charlson Comorbidity Index ≥3, acute kidney injury, end-stage renal disease, septic shock, acute respiratory failure, MV, and ICU status were independent predictors for mortality. Our study suggests that COVID-19 infection is an independent predictor of mortality in patients with cirrhosis, with threefold higher mortality and increased resource utilization. Early intervention through immunizations and advanced COVID-19 therapies can help improve these outcomes.

THU333 Race Was Not A Predictor Of Poor Outcomes From COVID-19 At University Of Chicago Medicine Hospital

Abstract Disclosure: A. Rashied: None. J. Cursio: None. E.C. Hanlon: None. S. Pannain: None. University of Chicago Medicine (UCM) is a large, 800 bed, urban hospital located on the south side of Chicago that cares for a substantial number of African-American (AA) patients. The COVID-19 pandemic has impacted health drastically, especially for minorities (including AAs) and those with comorbid conditions. We examined COVID outcomes in our UCM patient population, including patterns by race, other demographic information (age, sex), and comorbidities, and the relationship with deaths, intensive care unit (ICU), and mechanical ventilator use. From the period March 2020 to February 2021, 61.6% (11,071/17,945) patients tested for COVID-19 at UCM were positive, and 52.8% (5,850/11,071) of these were hospitalized for further care. Of these hospitalized patients 3,171 were AA and 2,679 were all other races. AA had a higher percentage of patients who were female (62% vs 54%, p&amp;lt;0.0001), were older (49 vs 43 years, p&amp;lt;0.0001), had longer hospital stays (13.5 vs 13.0 days, p&amp;lt;0.0001), were admitted to the ICU (9% vs 4%, p&amp;lt;0.0001), and died (5% vs 2%, p&amp;lt;0.0001) compared to non-AA patients. In addition, the rates of comorbid conditions were higher for AAs compared to non-AAs for hypertension (52% vs 32%, p&amp;lt;0.0001), heart disease (15% vs 9%, p&amp;lt;0.0001), diabetes (36% vs 22%, p&amp;lt;0.0001), kidney disease (21% vs 8%, p&amp;lt;0.0001), and obesity (53% vs 40%, p&amp;lt;0.0001). To explore the relationship of race and death among patients hospitalized with COVID-19, a predictive model for death was estimated including age, race, gender, hospital stay in days, ICU length of stay, and indicators for obesity, heart disease, kidney disease, hypertension, and diabetes. The model shows that AA adults have a higher odds ratio (OR=1.08, p=0.71) for death than non-AA adults, however the p-value was insignificant. Instead, significant predictors of death included age (OR=1.058, p&amp;lt;0.0001) and kidney disease (OR=2.108, p=0.0002). Neither diabetes nor obesity were significant predictors of death in our cohort. Race was also not a predictor of mechanical ventilation or ICU status. However, obesity, diabetes and kidney disease were all significant predictors of requiring ventilation (all p&amp;lt;0.05). Moreover, age (OR=1.013, p=0.001), female gender (OR=0.687, p=0.002), kidney disease (OR=2.431, p&amp;lt;0.0001), and diabetes (OR=2.224, p&amp;lt;0.0001) were significant predictors of ICU admission. The model for death, ventilator, and ICU status for patients with COVID-19 at UCM show increased risks for AA versus non-AAs, however the odds ratios were insignificant. Instead, comorbidities like kidney disease were a significant predicator of death, as were obesity and diabetes for COVID-19 related ventilation and ICU admission. Thus, in our patient population that includes a significant number of AA adults, race was not a predictor of poor COVID-19 outcomes, but kidney disease, obesity, and diabetes were – irrespective of race. Presentation: Thursday, June 15, 2023

Outcomes of Injured Patients Before and After the Institution of a Third-Tier Activation at a Level 1 Trauma Center.

We hypothesized that the addition of a third-level trauma activation would improve outcomes by formalizing an evaluation process for patients in need of urgent evaluation who did not meet the criteria for full or partial trauma alert activation. Admission records for all trauma patients admitted between 2000 and 2021 were obtained. The gamma alert trauma activation was implemented in 2011. A washout period of 6 months was used to account for adjustment to the new protocol. Propensity score matching was performed based on ISS scores, age, injury mechanism, and best-validated comorbidities to create a balanced patient distribution. Patients with missing data were excluded from this study. The association between era and outcomes was determined using logistic and linear regression analyses. The matched cohort was well balanced (SMD <.1, all balanced covariates) and included 18,572 patients. Patients in the gamma alert era had decreased ED dwell time, hospital length of stay, and intensive care unit (ICU) length of stay. Readmission rates and rates of upgrade to ICU status were reduced in the gamma alert era. This era was also associated with lower rates of renal failure, UTI, and pneumonia. There was no significant difference in mortality following implementation of the gamma alert. Implementation of the gamma alert was associated with an improvement in ED dwell times, fewer unplanned admissions to the ICU, decreased readmissions, and a reduction in other in-hospital events. We believe that this reflects improved triage of patients to the ICU and more effective care of trauma patients.

Health-related quality of life trajectories in critical illness: Protocol for a Monte Carlo simulation study.

Health-related quality of life (HRQoL) is a patient-centred outcome increasingly used as a secondary outcome in critical care research. It may cover several important dimensions of clinical status in intensive care unit (ICU) patients that arguably elude other more easily quantified outcomes such as mortality. Poor associations with harder outcomes, conflicting data on HRQoL in critically ill compared to the background population, and paradoxical effects on HRQoL and mortality complicate the current operationalisation in critical care trials. This protocol outlines a simulation study that will gauge if the areas under the HRQoL trajectories could be a viable alternative. We will gauge the behaviour of the proposed HRQoL operationalisation through Monte Carlo simulations, under clinical scenarios that reflect a broad critical care population eligible for inclusion in a large pragmatic trial. We will simulate 15,360 clinical scenarios based on a full factorial design with the following seven simulation parameters: number of patients per arm, relative mortality reduction in the interventional arm, acceleration of HRQoL improvement in the interventional arm, the relative improvement in final HRQoL in the interventional arm, dampening effect of mortality on HRQoL values at discharge from the ICU, proportion of so-called mortality benefiters in the interventional arm and mortality trajectory shape. For each clinical scenario, we will simulate 100,000 two-arm trials with 1:1 randomisation. HRQoL will be sampled fortnightly after ICU discharge. Outcomes will include HRQoL in survivors and all patients at the end of follow-up; mean areas under the HRQoL trajectories in both arms; and mean difference between areas under the HRQoL trajectories and single-sampled HRQoLs at the end of follow-up. In the outlined simulation study, we aim to assess whether the area under the HRQoL trajectory curve could be a candidate for reconciling the seemingly paradoxical effects on improved mortality and reduced HRQoL while remaining sensitive to early or accelerated improvement in patient outcomes. The resultant insights will inform subsequent methodological work on prudent collection and statistical analysis of such data from real critically ill patients.

CLinician and patient characteristics effect on Antimicrobial Stewardship Interventions (CLASI) study.

To determine whether the gender of clinicians making antimicrobial stewardship recommendations has an impact on intervention acceptance rate. A retrospective, multivariable analysis of antimicrobial stewardship prospective audit and feedback outcomes. A multisite healthcare system including Mayo Clinic Rochester (MN), Mayo Clinic Arizona, Mayo Clinic Florida and 17 health-system hospital sites, where prospective audit and feedback is performed and documented within an electronic tool embedded in the medical record. The study included 143 Mayo Clinic clinicians (84 cisfemales and 59 cismales). Outcomes were analyzed from July 1, 2017, to June 30, 2022, for intervention rates, communication methods, and intervention acceptance by clinician gender, profession, patient age, and intensive care unit (ICU) status of patient. Of 81,927 rules, 71,729 rules met study inclusion. There were 18,175 (25%) rules associated with an intervention. Most of the rules were reviewed by pharmacists (86.2%) and stewardship staff (85.5%). Of 10,363 interventions with an outcome documented, 8,829 (85.2%) were accepted and 1,534 (14.8%) were rejected. Female clinicians had 6,782 (86.5%) of 7,843 interventions accepted, and male clinicians had 2,047 (81.2%) of 2,520 interventions accepted (P = .19). Female patients had more interventions than male patients (female vs male: 25.9% vs 24.9%; OR, 1.04; 95% CI, 1.02-1.08; P = .001). Patients in the ICU had a significantly lower intervention acceptance rate (ICU vs non-ICU: 78.2% vs 86.7%; OR, 0.56; 95% CI, 0.45-0.7; P < .001). Female and male clinicians were equally effective at prospective audit and feedback in a multisite antimicrobial stewardship program. Patients in the ICU were less likely to have stewardship interventions accepted.

Clinical Outcomes With Extended Versus Intermittent Infusion of Anti-Pseudomonal Beta-Lactams in Patients With Gram-Negative Bacteremia.

Administration of doses via an extended infusion (EI) is an important strategy to optimize beta-lactams. Available data on the impact of EI on outcomes largely focus on clinical cure or mortality in critically ill patients or those with resistant pathogens. The potential benefits of EI extend beyond these populations and outcomes, and further study is warranted. This was a retrospective cohort study of adult patients who received cefepime, piperacillin/tazobactam, or meropenem for Gram-negative bacteremia via EI or intermittent infusion. Patients were matched 1:1 based on study drug, sepsis severity, intensive care unit (ICU) status, bacteremia source, and pathogen. Outcomes assessed included time to clinical stabilization, rates of treatment failure, mortality, recurrence, and length of stay (LOS). Two hundred sixty-eight patients were included. Baseline characteristics were similar between groups. Forty-two percent of patients were in the ICU at infection onset and the most common pathogen was Escherichia coli (41%). After adjusting for residual differences between groups, receipt of EI was independently associated with shorter time to clinical stability (adjusted odds ratio, 0.32; 95% confidence interval, .22-.47), time to defervescence, and time to white blood cell count normalization. Furthermore, EI was associated with a lower incidence of treatment failure, decreased recurrence of bacteremia, and shorter LOS. There was no difference in mortality. These findings were consistent regardless of patient location (ICU vs ward), baseline renal function, source of bacteremia, or study drug received. These findings suggest that EI beta-lactams are an important stewardship strategy to improve clinical outcomes in patients with Gram-negative bacteremia.

Weighted gene co-expression network analysis revealed T cell differentiation associated with the age-related phenotypes in COVID-19 patients

The risk of severe condition caused by Corona Virus Disease 2019 (COVID-19) increases with age. However, the underlying mechanisms have not been clearly understood. The dataset GSE157103 was used to perform weighted gene co-expression network analysis on 100 COVID-19 patients in our analysis. Through weighted gene co-expression network analysis, we identified a key module which was significantly related with age. This age-related module could predict Intensive Care Unit status and mechanical-ventilation usage, and enriched with positive regulation of T cell receptor signaling pathway biological progress. Moreover, 10 hub genes were identified as crucial gene of the age-related module. Protein–protein interaction network and transcription factors-gene interactions were established. Lastly, independent data sets and RT-qPCR were used to validate the key module and hub genes. Our conclusion revealed that key genes were associated with the age-related phenotypes in COVID-19 patients, and it would be beneficial for clinical doctors to develop reasonable therapeutic strategies in elderly COVID-19 patients.

Investigation of Delirium Occurrence and Intervention Status in Intensive Care Unit at a Hospital and Perception of Delirium by Medical Staff

Purpose : This study aims to investigate the status of delirium intervention in adult intensive care unit (ICU) patients and the perception of this delirium by medical staff.Methods : This retrospective study involves 185 patients, whereas, a descriptive survey is conducted with 197 medical staff members.Results : The delirium group includes 100 patients (54.1%). The incidence of delirium is 64.9% in the medical ICU, 65.9% in the surgical ICU, 42.4% in the neuro ICU, and 46.5% in the cardiac ICU. The percentages of delirium prevention intervention differs between the two groups: 65.0% in the delirium group and 95.3% in the non-delirium group. The medical staff recognize that delirium is a common problem in the ICU (100.0%) and requires active medical intervention (98.5%).Conclusion : The length of stay at the ICU is longer in the delirium group than in the non-delirium group. It is necessary to standardize delirium prevention and treatment protocols to be equally applicable to all ICU patients.

Effectiveness of intervention program on nurses’ practices about assessment of neonatal neurological status in neonatal intensive care unit

Objective: To evaluate nurses' practices regarding assessment of neonatal neurological status after an interventional program. Material: Pre-experimental study design was utilized, with a pre-, post-test 1 and post-test 2 methods. It was carried out from 9th January to 7th September, 2022. An instrument was developed for the purpose of the study. A non-probability, purposive sample of 30 nurses was recruited from nurses working at Neonatal Intensive Care Unit in Karbala Paediatric teaching hospital in the holy of Karbala City. The instrument had 47 items. Results: The overall evaluation of practice among nurses was poor level during the pre-test time (M±SD=8.77±3.29) among 96.7% nurses. The nurses’ practice improved after post-test 1(M±SD=37.43±8.83) among 73.3% of them and post-test 2 (M±SD=35.57±10.54) among 63.3% of them to good level after implementation the interventional program. Conclusion: Most nurses’ practices was poor but they scored at good level after application the interventional program, during the period of post-test 1 and 2.

Efficacy of continuous electroencephalogram for the management of altered mental status in the neurosurgical intensive care unit.

Continuous electroencephalograms (cEEGs) are often used in the neurosurgical intensive care unit (NSICU) to detect subclinical seizures (SCSs) in patients with altered mental status (AMS). This retrospective study evaluated the efficacy of this approach for improving patient outcomes. We reviewed the records of 100 patients admitted to the NSICU between 2015 and 2020 who underwent continous electroencephalograms (cEEG) during workup of unexplained AMS. Patient outcomes were classified as positive (discharged), neutral (transfer of care), or negative (dead). Incidence of SCSs on cEEG and association with patient outcomes was analyzed with Chi-square analysis and relative risk (RR). For the 99 included patients, median age was 62 years and 43% were female. About 15.2% had a known or newly diagnosed brain tumor. Outcomes were positive in 22 patients, neutral in four, and negative in 73. SCSs were detected in 15 patients, of whom 12 died, two were discharged, and one whose care was transferred. Chi-square association between SCS and outcome (P = 0.59) and RR of death associated with SCS diagnosis (1.1) was not significant. We found a lower incidence of SCSs (15.2%) than reported in the literature. In the absence of clinically evident seizures, continous cEEGs performed in the NSICU to determine the etiology of AMS did not yield an improvement in patient outcomes, and patients diagnosed and treated for SCS did not have statistically decreased risk of death. In summary, electroencephalogram monitoring for SCS is important but should not delay diagnosis and treatment of other, potentially life-threating etiologies of AMS.

786. Effect of Nirmatrelvir/Ritonavir versus Placebo on COVID-19─Related Hospitalizations and Other Medical Visits

Abstract Background Nirmatrelvir coadministered with ritonavir (nirmatrelvir/r) is a COVID-19 treatment. This study evaluated nirmatrelvir/r in nonhospitalized, symptomatic adults with COVID-19 at high risk of progressing to severe disease. We report secondary efficacy endpoints associated with COVID-19─related medical visits, including hospitalization details and oxygen support, as of the primary completion data cutoff (Dec 11, 2021). Methods In this phase 2/3 double-blind, interventional study, adults with confirmed SARS-CoV-2 and symptom onset ≤ 5 days (d) were randomized 1:1 to receive nirmatrelvir/r 300 mg/100 mg or placebo (PBO) orally every 12 hours for 5 d. COVID-19─related medical visits were collected through Day 28. Oxygen support for COVID-19 and details of COVID-19─related hospitalization, including duration, intensive care unit (ICU) status, and mechanical ventilation, were assessed. Results Of the 2246 patients (pts) enrolled globally from Jul to Dec2021, 2085 (nirmatrelvir/r, n=1039; PBO, n=1046) started treatment and met criteria for the modified intent-to-treat population (mITT1; ≤ 5 d of symptom onset, did not/not expected to receive a mAb). Fewer overall COVID-19-related medical visits were reported with nirmatrelvir/r vs PBO (Table 1). In addition to fewer hospitalizations being reported with nirmatrelvir/r (n=8 [0.8%]) vs PBO (n=65 [6.2%]), pts receiving nirmatrelvir/r had fewer hospitalized d (Table 2), with mean durations of 9.6 (range, 5.0, 16.0) d with nirmatrelvir/r and 11.2 (range, 2.0, 57.0) d with PBO in hospitalized pts. No pts in the nirmatrelvir/r group and 9 pts (0.9%) in PBO group were admitted to the ICU. No pts in the nirmatrelvir/r group received mechanical ventilation vs 3 pts in the PBO group. Fewer other COVID-19─related nonhospital medical visits were reported with nirmatrelvir/r vs PBO (Table 3). In the full analysis set, fewer pts required oxygen therapy for COVID-19 with nirmatrelvir/r (n=9/1120 [0.8%]) vs PBO (n=54/1126 [4.8%]). Conclusion High-risk adults with symptomatic COVID-19 treated with nirmatrelvir/r within 5 d of symptom onset had fewer COVID-19─related medical visits and reduced healthcare utilization (no ICU visits, no mechanical ventilation, fewer days in hospital) vs pts receiving PBO. Clinical Trial: NCT04960202. Disclosures Jennifer Hammond, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Heidi Leister-Tebbe, BSN, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Annie Gardner, MPH, MSPT, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Paula Abreu, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Weihang Bao, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Wayne Wisemandle, MA, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Wajeeha Ansari, MPH, Pfizer Inc.: Stocks/Bonds Rienk Pypstra, MD, MBA, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds James M Rusnak, MD, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds.

An Observational Study of Serum Vitamin D Status in Critically Ill Children Admitted to the Pediatric Intensive Care Unit

Introduction Vitamin D is a pleiotropic hormone involved in the functioning of organ systems including those central to critical illness pathophysiology. We evaluated the longitudinal vitamin D status in the pediatric intensive care unit (PICU) and its relevance to patient outcomes. Material and methods Thirty-six PICU-admitted patients, and 40 age- and sex-matched healthy children were enrolled. Serum total 25-hydroxyvitamin D [25(OH)D] levels were analyzed on PICU days 1, 5, and 10 in the patient group, and once in the control group. Patients were divided into sufficient (&gt;30 ng/mL), insufficient (20–30 ng/mL), and deficient (&lt;20 ng/mL) subgroups. Outcome measures between the subgroups and alterations in 25(OH)D levels were examined. Results The mean 25(OH)D levels of PICU patients initially and control cases were not different (25.4±6.0 and 25.9±5.8 ng/mL, respectively). Although all patients with vitamin D deficiency were hospitalized for infectious diseases, the mean 25(OH)D level of patients hospitalized for infections was not different from other patients. There was no difference between vitamin D subgroups in demographic variables, admission season, illness severity, respiratory/inotropic support, duration of stay, and mortality. Vitamin D deficient patients had lower albumin concentrations (p˂0.05). On days 5 and 10, the mean 25(OH)D levels of the patients were 24.5±5.7 and 23.6±5.8 ng/mL, respectively, both different from the admission level (p˂0.001). Conclusions Hypovitaminosis D, which is common in healthy children, is also common in PICU admission and tends to be more profound during the stay. Further studies are required to evaluate the bioavailability of vitamin D in critical illness.

The m7G Modification Level and Immune Infiltration Characteristics in Patients with COVID-19.

PurposeThe 7-methylguanosine (m7G)-related genes were used to identify the clinical severity and prognosis of patients with coronavirus disease 2019 (COVID-19) and to identify possible therapeutic targets.Patients and MethodsThe GSE157103 dataset provides the transcriptional spectrum and clinical information required to analyze the expression of m7G-related genes and the disease subtypes. R language was applied for immune infiltration analysis, functional enrichment analysis, and nomogram model construction.ResultsMost m7G-related genes were up-regulated in COVID-19 and were closely related to immune cell infiltration. Disease subtypes were grouped using a clustering algorithm. It was found that the m7G-cluster B was associated with higher immune infiltration, lower mechanical ventilation, lower intensive care unit (ICU) status, higher ventilator-free days, and lower m7G scores. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that differentially expressed genes (DEGs) between m7G-cluster A and B were enriched in viral infection and immune-related aspects, including COVID-19 infection; Th17, Th1, and Th2 cell differentiation, and human T-cell leukemia virus 1 infection. Finally, through machine learning, six disease characteristic genes, NUDT4B, IFIT5, LARP1, EIF4E, LSM1, and NUDT4, were screened and used to develop a nomogram model to estimate disease risk.ConclusionThe expression of most m7G genes was higher in COVID-19 patients compared with that in non-COVID-19 patients. The m7G-cluster B showed higher immune infiltration and milder symptoms. The predictive nomogram based on the six m7G genes can be used to accurately assess risk.

Pediatric Invasive Fungal Rhinosinusitis: A Comprehensive Analysis of Prognostic Factors for Survival.

Pediatric invasive fungal rhinosinusitis (IFS) is a devastating infection that manifests almost exclusively in immunocompromised children. The goal of this work was to determine which clinical features carry prognostic value for survival. A retrospective review of children with a histopathological diagnosis of IFS was performed at an academic tertiary care institution from 1990 to 2021. Clinical variables were collected to generate survival and life-table estimators at 6-months and 1-year. Eighteen patients were included in this analysis, with a mean age of 9.8 years (range, 1-17 years). Most children were neutropenic (n=15, 83.3%), with acute lymphoblastic leukemia (n=10, 55.6%) representing the most common primary diagnosis. A mean of 3.2 operations (range 1-7 operations) was performed per patient for either mucormycosis (n=10, 55.6%) or aspergillosis (n=8, 44.4%). The mean time to absolute neutrophil count recovery was 65.8 days (range 20-137 days), with a 6-month and 1-year survival rate of 47.6% and 41.7%, respectively. Gross total resection (p=0.006, p < 0.001), number of antifungals (p=0.0004, p=0.0003), and total operation number (p=0.0032, p=0.0035), served as positive prognostic factors for 6-month and 1-year survival. Conversely, altered mental status (p=0.0026), cerebral involvement (p=0.0010), cranial neuropathies (p < 0.0001), hyperglycemia (p=0.0445, p=0.0208), and intensive care unit status (p=0.0013) served as negative prognostic factors for 6-month and 1-year survival. Several key elements were identified and found to play a vital role in influencing survival for pediatric IFS. Early diagnosis, prompt medical therapy, and aggressive surgical intervention remain at the forefront in the treatment of this complex opportunistic infection. 4 Laryngoscope, 133:1239-1250, 2023.