The ROX, shock and diastolic shock indexes in the prediction of mortality in COVID-19.

OBJECTIVES: The aim of this study is to determine the role of Respiratory Rate Oxygenation (ROX), shock, and diastolic shock indexes ​​in predicting mortality in coronavirus disease 2019 (COVID-19) patients admitted to the emergency department. BACKGROUND: The COVID-19 spread worldwide in a short time and caused a major pandemic. The ROX, shock, and diastolic shock indexes are used in various life-threatening clinical situations. The use of these indexes in triage at emergency departments can accelerate the determination of COVID-19 patients' severity. METHODS: The ROX, shock and diastolic shock indices were calculated and recorded. Patients were divided into three groups; 1) who were discharged from the hospital, 2) who were admitted to the hospital and 3) who were admitted to the intensive care unit. RESULTS: Increased diastolic shock index and decreased ROX index were found to be independent risk factors for mortality. In the prediction of mortality, the sensitivity and specificity of the diastolic shock index were 61.2% and 60.8%, respectively. However, the sensitivity and specificity of ROX index was 73.1% and 71.5%, respectively. CONCLUSION: In conclusion, we found that the ROX index had higher sensitivity and specificity than other indexes in predicting mortality in the evaluation of COVID-19 patients (Tab. 3, Fig. 2, Ref. 18).

Synchronized lineage tracing of cell membranes and nuclei by dual recombinases and dual fluorescent.

Genetic lineage tracing has been widely employed to investigate cell lineages and fate. However, conventional reporting systems often label the entire cytoplasm, making it challenging to discern cell boundaries. Additionally, single Cre-loxP recombination systems have limitations in tracing specific cell populations. This study proposes three reporting systems that utilize Cre, Dre and Dre + Cre mediated recombination. These systems incorporate tdTomato expression on the cell membrane and PhiYFP expression within the cell nucleus, allowing for clear observation of the cell nucleus and membrane. The efficacy of these systems is successfully demonstrated by labeling cardiomyocytes and hepatocytes. The potential for dynamic visualization of the cell membrane is showcased using intravital imaging microscopy or three-dimensional imaging. Furthermore, by combining this dual recombinase system with the ProTracer system, hepatocyte proliferation is traced with enhanced precision. This reporting system holds significant importance in advancing the understanding of cell fate studies in development, homeostasis, and diseases.

NEWS2, S/F-ratio and ROX-index at emergency department for the prediction of adverse outcomes in COVID-19 patients: An external validation study.

BACKGROUND: In the context of the COVID-19 pandemic, the early and accurate identification of patients at risk of deterioration was crucial in overcrowded and resource-limited emergency departments. This study conducts an external validation for the evaluation of the performance of the National Early Warning Score 2 (NEWS2), the S/F ratio, and the ROX index at ED admission in a large cohort of COVID-19 patients from Colombia, South America, assessing the net clinical benefit with decision curve analysis. METHODS: A prospective cohort study was conducted on 6907 adult patients with confirmed COVID-19 admitted to a tertiary care ED in Colombia. The study evaluated the diagnostic performance of NEWS2, S/F ratio, and ROX index scores at ED admission using the area under the receiver operating characteristic curve (AUROC) for discrimination, calibration, and decision curve analysis for the prediction of intensive care unit admission, invasive mechanical ventilation, and in-hospital mortality. RESULTS: We included 6907 patients who presented to the ED with confirmed SARS-CoV-2 infection from March 2020 to November 2021. Mean age was 51 (35-65) years and 50.4% of patients were males. The rate of intensive care unit admission was 28%, and in-hospital death was 9.8%. All three scores have good discriminatory performance for the three outcomes based on the AUROC. S/F ratio showed miscalibration at low predicted probabilities and decision curve analysis indicated that the NEWS2 score provided a greater net benefit compared to other scores across at a 10% threshold to decide ED admission at a high-level of care facility. CONCLUSIONS: The NEWS2, S/F ratio, and ROX index at ED admission have good discriminatory performances in COVID-19 patients for the prediction of adverse outcomes, but the NEWS2 score has a higher net benefit underscoring its clinical utility in optimizing patient management and resource allocation in emergency settings.

Association between prehospital ROX index with 30-day mortality among septic shock.

PURPOSE: Respiratory dysfunction is one of the most frequent symptoms observed during sepsis reflecting hypoxemia and/or acidosis that may be assessed by the ROX index (ratio of oxygen saturation by pulse oximetry/fraction of inspired oxygen to respiratory rate). This study aimed to describe the relationship between the prehospital ROX index and 30-day mortality rate among septic shock patients cared for in the prehospital setting by a mobile intensive care unit (MICU). METHODS: From May 2016 to December 2021, 530 septic shock patients cared for by a prehospital MICU were retrospectively analysed. Initial ROX index value was calculated at the first contact with MICU. A Cox regression analysis after propensity score matching was performed to assess the relationship between 30-day mortality rate and a ROX index ≤ 10. RESULTS: Pulmonary, digestive and urinary sepsis were suspected among 43%, 25% and 17% patients, respectively. The 30-day overall mortality reached 31%. Cox regression analysis showed a significant association between 30-day mortality and a ROX index ≤ 10: adjusted hazard ratio of 1.54 [1.08-2.31], p < 0.05. CONCLUSIONS: During the prehospital stage of septic shock patients cared for by a MICU, ROX index is significantly associated with 30-day mortality. A prehospital ROX ≤ 10 value is associated with a 1.5-fold 30-day mortality rate increase. Prospective studies are needed to confirm the ability of prehospital ROX to predict sepsis outcome since the prehospital setting.

ChatGPT achieves comparable accuracy to specialist physicians in predicting the efficacy of high-flow oxygen therapy.

Background: The failure of high-flow nasal cannula (HFNC) oxygen therapy can necessitate endotracheal intubation in patients, making timely prediction of the intubation risk following HFNC therapy crucial for reducing mortality due to delays in intubation. Objectives: To investigate the accuracy of ChatGPT in predicting the endotracheal intubation risk within 48 h following HFNC therapy and compare it with the predictive accuracy of specialist and non-specialist physicians. Methods: We conducted a prospective multicenter cohort study based on the data of 71 adult patients who received HFNC therapy. For each patient, their baseline data and physiological parameters after 6-h HFNC therapy were recorded to create a 6-alternative-forced-choice questionnaire that asked participants to predict the 48-h endotracheal intubation risk using scale options ranging from 1 to 6, with higher scores indicating a greater risk. GPT-3.5, GPT-4.0, respiratory and critical care specialist physicians and non-specialist physicians completed the same questionnaires (N = 71) respectively. We then determined the optimal diagnostic cutoff point, using the Youden index, for each predictor and 6-h ROX index, and compared their predictive performance using receiver operating characteristic (ROC) analysis. Results: The optimal diagnostic cutoff points were determined to be ≥ 4 for both GPT-4.0 and specialist physicians. GPT-4.0 demonstrated a precision of 76.1 %, with a specificity of 78.6 % (95%CI = 52.4-92.4 %) and sensitivity of 75.4 % (95%CI = 62.9-84.8 %). In comparison, the precision of specialist physicians was 80.3 %, with a specificity of 71.4 % (95%CI = 45.4-88.3 %) and sensitivity of 82.5 % (95%CI = 70.6-90.2 %). For GPT-3.5 and non-specialist physicians, the optimal diagnostic cutoff points were ≥5, with precisions of 73.2 % and 64.8 %, respectively. The area under the curve (AUC) in ROC analysis for GPT-4.0 was 0.821 (95%CI = 0.698-0.943), which was the highest among the predictors and significantly higher than that of non-specialist physicians [0.662 (95%CI = 0.518-0.805), P = 0.011]. Conclusion: GPT-4.0 achieves an accuracy level comparable to specialist physicians in predicting the 48-h endotracheal intubation risk following HFNC therapy, based on patient baseline data and physiological parameters after 6-h HFNC therapy.

ROX Index Variation as a Predictor of Outcomes in COVID-19 Patients.

Background: During the COVID-19 pandemic, emergency departments were overcrowded with critically ill patients, and many providers were confronted with ethical dilemmas in assigning respiratory support to them due to scarce resources. Quick tools for evaluating patients upon admission were necessary, as many existing scores proved inaccurate in predicting outcomes. The ROX Index (RI), a rapid and straightforward scoring system reflecting respiratory status in acute respiratory failure patients, has shown promise in predicting outcomes for COVID-19 patients. The 24 h difference in the RI accurately gauges mortality and the need for invasive mechanical ventilation (IMV) among patients with COVID-19. Methods: Study design: Prospective cohort study. A total of 204 patients were admitted to the emergency department from May to August 2020. Data were collected from the clinical records. The RI was calculated at admission and 24 h later, and the difference was used to predict the association with mortality and the need for IMV, a logistic regression model was used to adjust for age, sex, presence of comorbidities, and disease severity. Finally, the data were analyzed using ROC. Results: The difference in respiratory RI between admission and 24 h is a good predictor for death (AUC 0.92) and for mechanic ventilation (AUC: 0.75). Each one-unit decrease in the RI difference at 24 h was associated with an odds ratio of 1.48 for the risk of death (95%CI: 1.31-1.67) and an odds ratio of 1.16 for IMV (95% IC: 1.1-1.23). Conclusions: The 24 h variation of RI is a good prediction tool to allow healthcare professionals to identify the patients who will benefit from invasive treatment, especially in low-resource settings.

Functional Role of C-terminal Domains in the MSL2 Protein of Drosophila melanogaster.

Dosage compensation complex (DCC), which consists of five proteins and two non-coding RNAs roX, specifically binds to the X chromosome in males, providing a higher level of gene expression necessary to compensate for the monosomy of the sex chromosome in male Drosophila compared to the two X chromosomes in females. The MSL2 protein contains the N-terminal RING domain, which acts as an E3 ligase in ubiquitination of proteins and is the only subunit of the complex expressed only in males. Functional role of the two C-terminal domains of the MSL2 protein, enriched with proline (P-domain) and basic amino acids (B-domain), was investigated. As a result, it was shown that the B-domain destabilizes the MSL2 protein, which is associated with the presence of two lysines ubiquitination of which is under control of the RING domain of MSL2. The unstructured proline-rich domain stimulates transcription of the roX2 gene, which is necessary for effective formation of the dosage compensation complex.

Effectiveness of early high-flow nasal oxygen therapy after extubation of patients in the intensive care unit.

PURPOSE: This study aimed to evaluate the impact of early high-flow nasal oxygen (HFNO) therapy initiation using a pre-determined respiratory rate­oxygenation (ROX) index on reducing reintubation rates and duration of intensive care unit (ICU) stay in post-extubated patients. MATERIALS AND METHODS: We enrolled a total of 145 extubated patients (mean age: 67.1 ± 12.9 years; sex: 96 male and 49 female; acute physiology and chronic health evaluation II score: 18.4 ± 6.8 points) classified into two groups: 71 patients admitted to the ICU before establishing extubation criteria and 74 patients after criteria implementation, over a 6-month period. We compared the HFNO reintubation rates and ROX index at 2 h post-extubation before and after implementing early HFNO criteria. RESULTS: The utilization rate of HFNO pre- and post-establishment of early HFNO criteria did not differ significantly (19.7% vs. 17.6%). However, the reintubation rate significantly decreased (11.3% vs. 4.1%, P < 0.05) with early HFNO use. Additionally, significant differences were observed in the total intubation period (5.2 ± 7.0 vs. 2.5 ± 2.7 days, P < 0.05) and ICU duration (8.6 ± 9.7 vs. 5.8 ± 5.6 days, P < 0.05). CONCLUSIONS: Early initiation of HFNO guided by the ROX index threshold post-extubation in patients admitted to ICU is associated with reduced reintubation rates and shorter ICU stays.

Spinning Disk Confocal Microscopy for Optimized and Quantified Live Imaging of 3D Mitochondrial Network.

Mitochondria are the energy factories of a cell, and depending on the metabolic requirements, the mitochondrial morphology, quantity, and membrane potential in a cell change. These changes are frequently assessed using commercially available probes. In this study, we tested the suitability of three commercially available probes-namely 5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolo-carbocyanine iodide (JC-1), MitoTracker Red CMX Rox (CMXRos), and tetramethylrhodamine methyl ester (TMRM)-for assessing the mitochondrial quantity, morphology, and membrane potential in living human mesoangioblasts in 3D with confocal laser scanning microscope (CLSM) and scanning disk confocal microscope (SDCM). Using CLSM, JC-1, and CMXRos-but not TMRM-uncovered considerable background and variation. Using SDCM, the background signal only remained apparent for the JC-1 monomer. Repetitive imaging of CMXRos and JC-1-but not TMRM-demonstrated a 1.5-2-fold variation in signal intensity between cells using CLSM. The use of SDCM drastically reduced this variation. The slope of the relative signal intensity upon repetitive imaging using CLSM was lowest for TMRM (-0.03) and highest for CMXRos (0.16). Upon repetitive imaging using SDCM, the slope varied from 0 (CMXRos) to a maximum of -0.27 (JC-1 C1). Conclusively, our data show that TMRM staining outperformed JC-1 and CMXRos dyes in a (repetitive) 3D analysis of the entire mitochondrial quantity, morphology, and membrane potential in living cells.

Respiratory Rate Oxygenation (ROX) index as predictor of high flow nasal cannula in pediatric patients in pediatric intensive care unit.

BACKGROUND: High-flow nasal cannula (HFNC) is often used in pediatric populations with respiratory distress. In adults, the respiratory-rate oxygenation (ROX) index is used as a predictor of HFNC therapy; however, children have age-associated differences in respiratory rate, thus may not be applicable to children. This study aims to find the reliability of ROX index and modified P-ROX index as predictors of HFNC therapy failure in pediatric patients. METHODS: Subjects in this analytical cross-sectional study were taken from January 2023 until November 2023 in Cipto Mangunkusumo Hospital. Inclusion criteria are children aged 1 month to 18 years with respiratory distress and got HFNC therapy. Receiver operating characteristics (ROC) analysis was used to find mP-ROX index cutoff value as a predictor of HFNC failure. The area under curve (AUC) score of mP-ROX index was assessed at different time point. RESULTS: A total of 102 patients, with 70% of the population with pneumonia, were included in this study. There are significant differences in the ROX index between the successful and failed HFNC group therapy (p < 0.05). This study suggests that mP-ROX index is not useful as predictor of HFNC therapy in pediatrics. While ROX index < 5.52 at 60 min and < 5.68 at 90 min after HFNC initiation have a sensitivity of 90% and specificity of 71%, sensitivity of 78% and specificity of 76%, respectively. CONCLUSION: mP-ROX index is not useful as a predictor of HFNC therapy in pediatrics. Meanwhile, ROX index at 60 min and 90 min after initiation of HFNC is useful as a predictor of HFNC failure.

siRNA that participates in Drosophila dosage compensation is produced by many 1.688X and 359†bp repeats.

Organisms with differentiated sex chromosomes must accommodate unequal gene dosage in males and females. Male fruit flies increase X-linked gene expression to compensate for hemizygosity of their single X chromosome. Full compensation requires localization of the Male-Specific Lethal (MSL) complex to active genes on the male X, where it modulates chromatin to elevate expression. The mechanisms that identify X chromatin are poorly understood. The euchromatic X is enriched for AT-rich, ∼359 bp satellites termed the 1.688X repeats. Autosomal insertions of 1.688X DNA enable MSL recruitment to nearby genes. Ectopic expression of dsRNA from one of these repeats produces siRNA and partially restores X-localization of MSLs in males with defective X recognition. Surprisingly, expression of double-stranded RNA from three other 1.688X repeats failed to rescue males. We reconstructed dsRNA-expressing transgenes with sequence from two of these repeats and identified phasing of repeat DNA, rather than sequence or orientation, as the factor that determines rescue of males with defective X recognition. Small RNA sequencing revealed that siRNA was produced in flies with a transgene that rescues, but not in those carrying a transgene with the same repeat but different phasing. We demonstrate that pericentromeric X heterochromatin promotes X recognition through a maternal effect, potentially mediated by small RNA from closely related heterochromatic repeats. This suggests that the sources of siRNAs promoting X recognition are highly redundant. We propose that enrichment of satellite repeats on Drosophilid X chromosomes facilitates the rapid evolution of differentiated sex chromosomes by marking the X for compensation.

Retrospective evaluation of the respiratory rate-oxygenation index to predict the outcome of high-flow nasal cannula oxygen therapy in dogs (2018-2021): 81 cases.

OBJECTIVE: To evaluate the respiratory rate-oxygenation index (ROX), modified ROX index (ROX-HR), and the ratio of pulse oximetry saturation (Spo2) to Fio2 (SF) to determine if these indices over time are predictive of outcome in dogs treated with high-flow nasal cannula oxygen therapy (HFNC). DESIGN: Retrospective study. SETTING: Two university teaching hospitals. ANIMALS: Eighty-one client-owned dogs treated with HFNC for hypoxemic respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The ROX was defined as the SF divided by the respiratory rate (RR), and the ROX-HR was defined as the ROX divided by the heart rate multiplied by 100. The overall success rate of HFNC was 44% (n = 36/81). Dogs weaned from HFNC had a significantly higher ROX (P < 0.0001) at 1-3, 5-10, 12, and 15 hours than dogs that failed HFNC. Both the ROX and SF showed excellent discriminatory power in predicting HFNC failure at 6 hours, with an area under receiver operating curve of 0.85 (95% confidence interval: 0.72-0.99; P < 0.002) and 0.86 (95% confidence interval: 0.73-0.99; P < 0.001), respectively. The optimal cutoff values for predicting HFNC failure at 6 hours were a ROX ≤3.68 (sensitivity 72%, specificity 92%) and an SF ≤143 (sensitivity 79%, specificity 93%). CONCLUSIONS: These results suggest that similar to people, the ROX and SF are useful predictors of HFNC failure. These indices are easy to measure at the bedside and may have clinical use. Future prospective studies are warranted to confirm the findings and to optimize cutoff values in a larger population of dogs undergoing HFNC.

A knock-in allele of Hand2 expressing Dre recombinase.

HAND2 is a basic helix-loop-helix transcription factor with diverse functions during development. To facilitate the investigation of genetic and functional diversity among Hand2-expressing cells in the mouse, we have generated Hand2Dre, a knock-in allele expressing Dre recombinase. To avoid disrupting Hand2 function, the Dre cDNA is inserted at the 3' end of the Hand2 coding sequence following a viral 2A peptide. Hand2Dre homozygotes can therefore be used in complex crosses to increase the proportion of useful genotypes among offspring. Dre expression in mid-gestation Hand2Dre embryos is indistinguishable from wild-type Hand2 expression, and HandDre efficiently recombines rox target sites in vivo. In combination with existing Cre and Flp mouse lines, Hand2Dre will therefore extend the ability to perform genetic intersectional labeling, fate mapping, and functional manipulation of subpopulations of cells characterized by developmental expression of Hand2.

A pragmatic calibration of the ROX index to predict outcome of nasal high-flow therapy in India.

PURPOSE: Identifying thresholds at which the ROX index would satisfactorily predict HFNC failure across heterogenous resourced contexts is necessary for clinical use. METHODS: Patients ≥18 years admitted to 30 diverse ICUs across 10 states in India who required HFNC for respiratory support were retrospectively included in this study. Patient data and hourly ROX indices were then analyzed and contextualized to clinical outcomes as well as with ROX index thresholds in other regions of the world. MEASUREMENTS AND MAIN RESULTS: Among the 614 patients included, 276 (44.9%) required respiratory escalation. Pneumonia was the most common diagnosis on admission. Receiver operating characteristic curve analysis revealed that a baseline ROX score of 7.86 was similar to 4.88 in other populations which was confirmed by Kaplan-Mier curves (hazard ratio,3.58 (2.72-4.69, p < 0.001)). ROX scores at 11.84 or 5.89 had roles in screening and confirming HFNC failure. The index performed poorly in a subset of patients who died without respiratory escalation. The ROX index was most predictive in the initial hours of ICU admission and a longer duration of HFNC was associated with more severe outcomes. CONCLUSIONS: When optimally calibrated this index can using a method that can reliably predict the risk of HFNC failure among ICU patients from diverse settings.

Using the ROX Index to Predict Treatment Outcome for High-Flow Nasal Cannula and/or Noninvasive Ventilation in Patients With COPD Exacerbations.

BACKGROUND: The ratio of oxygen saturation index (ROX index; or SpO2 /FIO2 /breathing frequency) has been shown to predict risk of intubation after high-flow nasal cannula (HFNC) support among adults with acute hypoxemic respiratory failure primarily due to pneumonia. However, its predictive value for other subtypes of respiratory failure is unknown. This study investigated whether the ROX index predicts liberation from HFNC or noninvasive ventilation (NIV), intubation with mechanical ventilation, or death in adults admitted for respiratory failure due to an exacerbation of COPD. METHODS: We performed a retrospective study of 260 adults hospitalized with a COPD exacerbation and treated with HFNC and/or NIV (continuous or bi-level). ROX index scores were collected at treatment initiation and predefined time intervals throughout HFNC and/or NIV treatment or until the subject was intubated or died. A ROX index score of ≥ 4.88 was applied to the cohort to determine if the same score would perform similarly in this different cohort. Accuracy of the ROX index was determined by calculating the area under the receiver operator curve. RESULTS: A total of 47 subjects (18%) required invasive mechanical ventilation or died while on HFNC/NIV. The ROX index at treatment initiation, 1 h, and 6 h demonstrated the best prediction accuracy for avoidance of invasive mechanical ventilation or death (area under the receiver operator curve 0.73 [95% CI 0.66-0.80], 0.72 [95% CI 0.65-0.79], and 0.72 [95% CI 0.63-0.82], respectively). The optimal cutoff value for sensitivity (Sn) and specificity (Sp) was a ROX index score > 6.88 (sensitivity 62%, specificity 57%). CONCLUSIONS: The ROX index applied to adults with COPD exacerbations treated with HFNC and/or NIV required higher scores to achieve similar prediction of low risk of treatment failure when compared to subjects with hypoxemic respiratory failure/pneumonia. ROX scores < 4.88 did not accurately predict intubation or death.

Association between the ROX index and mortality in patients with acute hypoxemic respiratory failure: a retrospective cohort study.

BACKGROUND: Although ROX index is frequently used to assess the efficacy of high-flow nasal cannula treatment in acute hypoxemic respiratory failure (AHRF) patients, the relationship between the ROX index and the mortality remains unclear. Therefore, a retrospective cohort study was conducted to evaluate the ability of the ROX index to predict mortality risk in patients with AHRF. METHOD: Patients diagnosed with AHRF were extracted from the MIMIC-IV database and divided into four groups based on the ROX index quartiles. The primary outcome was 28-day mortality, while in-hospital mortality and follow-up mortality were secondary outcomes. To investigate the association between ROX index and mortality in AHRF patients, restricted cubic spline curve and COX proportional risk regression were utilized. RESULT: A non-linear association (L-shaped) has been observed between the ROX index and mortality rate. When the ROX index is below 8.28, there is a notable decline in the 28-day mortality risk of patients as the ROX index increases (HR per SD, 0.858 [95%CI 0.794-0.928] P < 0.001). When the ROX index is above 8.28, no significant association was found between the ROX index and 28-day mortality. In contrast to the Q1 group, the mortality rates in the Q2, Q3, and Q4 groups had a substantial reduction (Q1 vs. Q2: HR, 0.749 [0.590-0.950] P = 0.017; Q3: HR, 0.711 [0.558-0.906] P = 0.006; Q4: HR, 0.641 [0.495-0.830] P < 0.001). CONCLUSION: The ROX index serves as a valuable predictor of mortality risk in adult patients with AHRF, and that a lower ROX index is substantially associated with an increase in mortality.

Identification of X chromatin is modulated by complementary pathways in Drosophila melanogaster.

Drosophila melanogaster males have one X chromosome while females have two. This creates an imbalance in X:A gene dosage between the sexes. This imbalance is corrected by increasing transcription from male X-linked genes approximately 2-fold. This process involves the Male-Specific Lethal (MSL) complex, which is recruited to Chromatin Entry Sites (CES) and transcribed X-linked genes, where it modifies chromatin to increase expression. Repetitive sequences strikingly enriched in X euchromatin, the 1.688X satellite repeats, also promote recruitment of the MSL complex to nearby genes. Unlike CES, the 1.688X repeats do not recruit the MSL complex directly. The genetic architecture of recruitment by these DNA elements remains speculative. To facilitate dissection of the mechanism of recruitment, we developed a luciferase reporter system for recruitment of compensation to an autosome. The system was validated by knock down of genes known to participate in compensation. Knock down of factors genetically linked to X recognition reveals that 1.688X repeats recruit through a different mechanism than the CES. Our findings suggest that 1.688X repeats play a larger role during embryogenesis, whereas the contribution of 1.688X repeats and CES is equivalent later in development. Our studies also reveal unexpected complexity and potential interdependence of recruiting elements.

High-Flow Nasal Cannula in COVID-19 Patients With Moderate to Severe Respiratory Distress: A Retrospective Analysis.

BACKGROUND: A high-flow nasal cannula (HFNC) is a device for non-invasive ventilation (NIV). It was utilized during the COVID-19 pandemic in patients with moderate to severe respiratory distress due to its benefit profile in delaying intubation, ease of use, and comfort of patients in comparison to NIV. OBJECTIVES: Our main objective is to calculate the intubation rate of patients with suspected or lab-confirmed COVID-19 in moderate to severe respiratory distress who failed graded oxygen therapy (GOT). Before incorporating HFNC as a treatment option, the intubation rate was 100% after GOT failure. We calculated the rate of intubation at two, six, and 12 hours of starting HFNC, where each patient is in their own control with an assumed intubation rate of 100%. Other objectives include measuring the rate of improvement of the ROX index, respiratory rate (RR), and oxygen saturation (SPO2) levels at two, six, and 12 hours. METHODS: We retrospectively screened patients with suspected or lab-confirmed COVID-19 infection in moderate to severe respiratory distress at Rashid Hospital Trauma Center, Emergency Department in Dubai, United Arab Emirates, from April 10, 2020, until December 31, 2020. The list of patients was pooled from the SALAMA electronic system. RESULTS: A total of 121 patients were included in the analysis. Assuming an intubation rate of 100% at 0 hours (end of GOT), after starting HFNC, the intubation rate (primary outcome) at two hours was 7.43% (9/121), at six hours was 7.14% (8/112), and at 12 hours was 5.77% (6/104). The total intubation rate at 12 hours was 19% (23/121). The use of HFNC was also shown to improve the ROX index, RR, and SPO2 at two, six, and 12 hours. CONCLUSION: In patients with suspected or lab-confirmed COVID-19 in moderate to severe respiratory distress who failed GOT and were started on HFNC, it was noted that the intubation rate decreased from an assumed rate of 100% to 19% at 12 hours from starting the treatment. There was also a statistically significant improvement in the ROX index, SPO2, and RR at two, six, and 12 hours from the initiation at 0 hours.

External validation of the HACOR score and ROX index for predicting treatment failure in patients with coronavirus disease 2019 pneumonia managed on high-flow nasal cannula therapy: a multicenter retrospective observational study in Japan.

BACKGROUND: The HACOR score for predicting treatment failure includes vital signs and acid-base balance factors, whereas the ROX index only considers the respiratory rate, oxygen saturation, and fraction of inspired oxygen (FiO2). We aimed to externally validate the HACOR score and ROX index for predicting treatment failure in patients with coronavirus disease 2019 (COVID-19) on high-flow nasal cannula (HFNC) therapy in Japan. METHODS: This retrospective, observational, multicenter study included patients, aged ≥ 18 years, diagnosed with COVID-19 and treated with HFNC therapy between January 16, 2020, and March 31, 2022. The HACOR score and ROX index were calculated at 2, 6, 12, 24, and 48 h after stating HFNC therapy. The primary outcome was treatment failure (requirement for intubation or occurrence of death within 7 days). We calculated the area under the receiver operating characteristic curve (AUROC) and assessed the diagnostic performance of these indicators. The 2-h time-point prediction was considered the primary analysis and that of other time-points as the secondary analysis. We also assessed 2-h time-point sensitivity and specificity using previously reported cutoff values (HACOR score > 5, ROX index < 2.85). RESULTS: We analyzed 300 patients from 9 institutions (median age, 60 years; median SpO2/FiO2 ratio at the start of HFNC therapy, 121). Within 7 days of HFNC therapy, treatment failure occurred in 127 (42%) patients. The HACOR score and ROX index at the 2-h time-point exhibited AUROC discrimination values of 0.63 and 0.57 (P = 0.24), respectively. These values varied with temporal changes-0.58 and 0.62 at 6 h, 0.70 and 0.68 at 12 h, 0.68 and 0.69 at 24 h, and 0.75 and 0.75 at 48 h, respectively. The 2-h time-point sensitivity and specificity were 18% and 91% for the HACOR score, respectively, and 3% and 100% for the ROX index, respectively. Visual calibration assessment revealed well calibrated HACOR score, but not ROX index. CONCLUSIONS: In COVID-19 patients receiving HFNC therapy in Japan, the predictive performance of the HACOR score and ROX index at the 2-h time-point may be inadequate. Furthermore, clinicians should be mindful of time-point scores owing to the variation of the models' predictive performance with the time-point. Trial registration UMIN (registration number: UMIN000050024, January 13, 2023).

Evaluation of HACOR scale as a predictor of non-invasive ventilation failure in acute cardiogenic pulmonary oedema patients: A prospective observational study.

BACKGROUND AND IMPORTANCE: Acute cardiogenic pulmonary oedema (ACPO) is a common indication for non-invasive ventilation (NIV) in the emergency department (ED). HACOR score of >5 is used to predict NIV failure. The predictive ability of HACOR may be affected by altered physiological parameters in ACPO patients due to medications or comorbidities. OBJECTIVES: To validate the HACOR scale in predicting NIV failure among acute cardiogenic pulmonary oedema (ACPO) patients. DESIGN, SETTINGS AND PARTICIPANTS: This is a prospective, observational study of consecutive ACPO patients requiring NIV admitted to the ED. OUTCOME MEASURE AND ANALYSIS: Primary outcome was the ability of the HACOR score to predict NIV failure. Clinical, physiological, and HACOR score at baseline and at 1 h, 12 h and 24 h were analysed. Other potential predictors were assessed as secondary outcomes. MAIN RESULTS: A total of 221 patients were included in the analysis. Fifty-four (24.4%) had NIV failure. Optimal HACOR score was >5 at 1 h after NIV initiation in predicting NIV failure (AUC 0.73, sensitivity 53.7%, specificity 83.2%). As part of the HACOR score, respiratory rate and heart rate were not found to be significant predictors. Other significant predictors of NIV failure in ACPO patients were acute coronary syndrome, acute kidney injury, presence of congestive heart failure as a comorbid, and the ROX index. CONCLUSIONS: The HACOR scale measured at 1 h after NIV initiation predicts NIV failure among ACPO patients with acceptable accuracy. The cut-off level > 5 could be a useful clinical decision support tool in ACPO patient. However, clinicians should consider other factors such as the acute coronary and acute kidney diagnosis at presentation, presence of underlying congestive heart failure and the ROX index when clinically deciding on timely invasive mechanical ventilation.