Novel autoantibodies help diagnose anti-SSA antibody negative Sjögren disease and predict abnormal labial salivary gland pathology.

OBJECTIVES: Sjögren disease (SjD) diagnosis often requires either positive anti-SSA antibodies or a labial salivary gland biopsy with a positive focus score (FS). One-third of patients with SjD lack anti-SSA antibodies (SSA-), requiring a positive FS for diagnosis. Our objective was to identify novel autoantibodies to diagnose 'seronegative' SjD. METHODS: IgG binding to a high-density whole human peptidome array was quantified using sera from SSA- SjD cases and matched non-autoimmune controls. We identified the highest bound peptides using empirical Bayesian statistical filters, which we confirmed in an independent cohort comprising SSA- SjD (n=76), sicca-controls without autoimmunity (n=75) and autoimmune-feature controls (SjD features but not meeting SjD criteria; n=41). In this external validation, we used non-parametric methods for binding abundance and controlled false discovery rate in group comparisons. For predictive modelling, we used logistic regression, model selection methods and cross-validation to identify clinical and peptide variables that predict SSA- SjD and FS positivity. RESULTS: IgG against a peptide from D-aminoacyl-tRNA deacylase (DTD2) bound more in SSA- SjD than sicca-controls (p=0.004) and combined controls (sicca-controls and autoimmune-feature controls combined; p=0.003). IgG against peptides from retroelement silencing factor-1 and DTD2 were bound more in FS-positive than FS-negative participants (p=0.010; p=0.012). A predictive model incorporating clinical variables showed good discrimination between SjD versus control (area under the curve (AUC) 74%) and between FS-positive versus FS-negative (AUC 72%). CONCLUSION: We present novel autoantibodies in SSA- SjD that have good predictive value for SSA- SjD and FS positivity.

Differential changes in expression of inflammatory mRNA and protein after oleic acid-induced acute lung injury.

Background: Acute Respiratory Distress syndrome (ARDS) is a clinical syndrome of noncardiac pulmonary edema and inflammation leading to acute respiratory failure. We used the oleic acid infusion pig model of ARDS resembling human disease to explore cytokine changes in white blood cells (WBC) and plasma proteins, comparing baseline to ARDS values. Methods: Nineteen juvenile female swine were included in the study. ARDS defined by a PaO2/FiO2 ratio < 300 was induced by continuous oleic acid infusion. Arterial blood was drawn before and during oleic acid infusion, and when ARDS was established. Cytokine expression in WBC was analyzed by RT-qPCR and plasma protein expression by ELISA. Results: The median concentration of IFN-γ mRNA was estimated to be 59% (p = 0.006) and of IL-6 to be 44.4% (p = 0.003) of the baseline amount. No significant changes were detected for TNF-α, IL-17, and IL-10 mRNA expression. In contrast, the concentrations of plasma IFN-γ and IL-6 were significantly higher (p = 0.004 and p = 0.048 resp.), and TNF-α was significantly lower (p = 0.006) at ARDS compared to baseline. Conclusions: The change of proinflammatory cytokines IFN-γ and IL-6 expression is different comparing mRNA and plasma proteins at oleic acid-induced ARDS compared to baseline. The migration of cells to the lung may be the cause for this discrepancy.

Validation of Thermal Imaging and the ALT-70 Prediction Model to Differentiate Cellulitis From Pseudocellulitis.

Importance: Cellulitis is misdiagnosed in up to 30% of cases due to mimic conditions termed pseudocellulitis. The resulting overuse of antibiotics is a threat to patient safety and public health. Surface thermal imaging and the ALT-70 (asymmetry, leukocytosis, tachycardia, and age ≥70 years) prediction model have been proposed as tools to help differentiate cellulitis from pseudocellulitis. Objectives: To validate differences in skin surface temperatures between patients with cellulitis and patients with pseudocellulitis, assess the optimal temperature measure and cut point for differentiating cellulitis from pseudocellulitis, and compare the performance of skin surface temperature and the ALT-70 prediction model in differentiating cellulitis from pseudocellulitis. Design, Setting, and Participants: This prospective diagnostic validation study was conducted among patients who presented to the emergency department with acute dermatologic lower extremity symptoms from October 11, 2018, through March 11, 2020. Statistical analysis was performed from July 2020 to March 2021 with additional work conducted in September 2023. Main Outcomes and Measures: Temperature measures for affected and unaffected skin were obtained. Cellulitis vs pseudocellulitis was assessed by a 6-physician, independent consensus review. Differences in temperature measures were compared using the t test. Logistic regression was used to identify the temperature measure and associated cut point with the optimal performance for discriminating between cellulitis and pseudocellulitis. Diagnostic performance characteristics for the ALT-70 prediction model, surface skin temperature, and both combined were also assessed. Results: The final sample included 204 participants (mean [SD] age, 56.6 [16.5] years; 121 men [59.3%]), 92 (45.1%) of whom had a consensus diagnosis of cellulitis. There were statistically significant differences in all skin surface temperature measures (mean temperature, maximum temperature, and gradients) between cellulitis and pseudocellulitis. The maximum temperature of the affected limb for patients with cellulitis was 33.2 °C compared with 31.2 °C for those with pseudocellulitis (difference, 2.0 °C [95% CI, 1.3-2.7 °C]; P < .001). The maximum temperature was the optimal temperature measure with a cut point of 31.2 °C in the affected skin, yielding a mean (SD) negative predictive value of 93.5% (4.7%) and a sensitivity of 96.8% (2.3%). The sensitivity of all 3 measures remained above 90%, while specificity varied considerably (ALT-70, 22.0% [95% CI, 15.8%-28.1%]; maximum temperature of the affected limb, 38.4% [95% CI, 31.7%-45.1%]; combination measure, 53.9% [95% CI, 46.5%-61.2%]). Conclusions and Relevance: In this large diagnostic validation study, significant differences in skin surface temperature measures were observed between cases of cellulitis and cases of pseudocellulitis. Thermal imaging and the ALT-70 both demonstrated high sensitivity, but specificity was improved by combining the 2 measures. These findings support the potential of thermal imaging, alone or in combination with the ALT-70 prediction model, as a diagnostic adjunct that may reduce overdiagnosis of cellulitis.

Cervical Cancer and a History of Incarceration: Examining a Social Determinant of Health.

Females who are incarcerated are disproportionately burdened by cancer, particularly cervical cancer. We measured the odds of cervical cancer compared with nonscreenable cancers for females who were incarcerated before diagnosis. By comparing a cancer for which screening and vaccination are available with cancers for which neither are available, we aimed to assess the relationship of incarceration with diseases for which preventive care mitigates risk. We created a novel data set combining cancer data from a large cancer center with incarceration data from the state department of corrections. We then estimated the odds of cervical cancer relative to nonscreenable cancers for those with and without a history of incarceration. Females with a history of incarceration had greater odds of being diagnosed with cervical cancer compared with nonscreenable cancers (odds ratio = 7.04; 95% confidence interval [CI]: 4.4-11.0) relative to those who had not been incarcerated. Adjusting for race and age, the odds of cervical cancer remained significantly greater for those with a history of incarceration (adjusted odds ratio = 3.86; 95% CI: 2.3-6.3). Our findings support the need for expanded cervical cancer screening and vaccination opportunities for incarcerated females and increased access to preventive health care after release.

Decreased Intraoperative Renal Tissue Oxygenation after Cardiopulmonary Bypass Predicts Cardiac Surgery-Associated Acute Kidney Injury in Neonates.

(1) Background: Near-infrared spectroscopy (NIRS) is a noninvasive tool frequently used during cardiac surgery and postoperatively in the cardiac intensive care unit to monitor regional tissue oxygen saturation. A relationship between trends of intraoperative renal oxygenation and the risk of developing cardiac surgery-associated acute kidney injury (AKI) post-operatively has not yet been established in the neonatal population. The objective of this study is to evaluate the relationship of cerebral and renal oxygenation during cardiopulmonary bypass with cardiac surgery-associated AKI in the first 72 h post-operation in neonates < 30 days of age. (2) Methods: A prospective cohort study at a tertiary care children's hospital was performed. Renal and cerebral oxygenation measured were collected intraoperatively from neonates < 30 days of age who underwent cardiopulmonary bypass for the correction of congenital heart disease. AKI was defined accordance with the Kidney Disease: Improving Global Outcomes criteria modified for neonates. Variables were compared between groups. (3) Results: 32 neonates with 35 cardiopulmonary bypass cases were included. AKI was diagnosed in 60% of cases. Intra-operative renal oxygenation, both on- and off-bypass, did not differ among the three AKI groups (p > 0.19). Renal oxygenation after coming off, but not during, cardiopulmonary bypass steadily decreased with increasing levels of AKI (Jonckheere's test, one-sided p = 0.024). (4) Conclusions: Renal oxygenation decreased in proportion to AKI severity after coming off, but not during, cardiopulmonary bypass.

A novel factor IXa-specific enzyme-linked immunosorbent assay detects factor IXa in human plasma.

Background: Factor (F)IXa activity has been detected in human plasma and may impact thrombotic risk. Current FIXa activity assays are complex and cumbersome. Objectives: To develop a reproducible enzyme-linked immunosorbent assay (ELISA) using a novel monoclonal antibody that detects total FIXa in human plasma. Methods: A monoclonal antibody was raised against the new N-terminus exposed upon activation of FIX to FIXa by cleavage after R226. This antibody is specific for FIXa protease and does not recognize FIX zymogen or FIXα. The antibody was used to develop a FIXa-specific ELISA capable of quantifying total FIXa (free FIXa and FIXa-antithrombin complex) in human plasma. Total FIXa quantified using the ELISA was compared to that of FIXa-antithrombin quantified using modifications of a previously described ELISA. Results: The FIXa-specific ELISA was reproducible and quantified total FIXa in human plasma. Total FIXa levels correlated with FIXa-antithrombin levels. Conclusion: A monoclonal antibody was developed that specifically detects human FIXa protease. A FIXa-specific ELISA using the new antibody is capable of reproducibly measuring total FIXa in human plasma (both free FIXa and FIXa-antithrombin). This assay should facilitate the evaluation of total FIXa levels in a variety of clinical circumstances.

Comparison of preoperative retrobulbar bupivacaine and postoperative subcutaneous liposome-encapsulated bupivacaine on postoperative analgesia in dogs undergoing enucleation.

OBJECTIVE: To compare the effectiveness of preoperative bupivacaine inferotemporal retrobulbar blocks to postoperative liposome-encapsulated bupivacaine (Nocita) line blocks for analgesia following enucleation. ANIMALS: 39 client-owned dogs (40 eyes) presenting to the Ophthalmology Service for enucleation. METHODS: Dogs were randomly assigned to receive either a preoperative inferotemporal retrobulbar block with 0.5% bupivacaine or a peri-incisional line block with liposome-encapsulated bupivacaine (Nocita) at closure. Patients underwent unilateral enucleation and were hospitalized for 24 hours after surgery. Pain scores were performed by a masked observer with the Glasgow Composite Measure Pain Scale and the University of Wisconsin Ocular Pain Scale at 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours following surgery. Intraoperative use of blood pressure and anesthetic support mediations as well as need for rescue pain control were recorded and compared between groups. RESULTS: There was no significant difference in rescue rates between treatment groups. When comparing the use of medical intraoperative heart rate, blood pressure, or anesthetic plane support, there were no significant differences in use between groups. CLINICAL RELEVANCE: Use of preoperative bupivacaine retrobulbar blocks and postoperative Nocita line blocks were equally effective at postoperative pain control with similarly low complication rates.

Renal tissue oxygenation and development of AKI in preterm neonates born < 32 weeks' gestational age in the first week of age.

OBJECTIVE: To evaluate the relationship between regional renal saturation of oxygen (RrSO2) changes and serum creatinine (SCr) during the first eight days of age for preterm neonates born < 32 weeks' gestational age. DESIGN: Post-hoc analysis of multicenter prospectively measured neonatal RrSO2 values collected during the first 8 days of age in neonates born at < 32 weeks' gestation. Acute kidney injury (AKI) was defined by the neonatal modified Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Variables were compared between groups of neonates with and with AKI. RESULTS: One hundred nine neonates were included and 561 SCr values were obtained. Eight participants developed AKI by SCr criteria. A 10-percentage point increase in mean %RrSO2 was associated with a 40% decrease in risk of AKI (95%CI: 9.6-61%; p = 0.016). CONCLUSIONS: Increases in mean %RrSO2 in neonates born at < 32 weeks' GA were associated with a decreased risk of AKI. These findings support the design of further prospective trials utilizing RrSO2 monitoring to evaluate new therapies or clinical protocols to prevent and treat neonatal AKI.

Neutrophil motility is regulated by both cell intrinsic and endothelial cell ARPC1B.

Neutrophil-directed motility is necessary for host defense, but its dysregulation can also cause collateral tissue damage. Actinopathies are monogenic disorders that affect the actin cytoskeleton and lead to immune dysregulation. Deficiency in ARPC1B, a component of the Arp2/3 complex, results in vascular neutrophilic inflammation; however, the mechanism remains unclear. Here, we generated human induced pluripotent stem cell (iPSC)-derived neutrophils (denoted iNeutrophils) that are deficient in ARPC1B and show impaired migration and a switch from forming pseudopodia to forming elongated filopodia. We show, using a blood vessel on a chip model, that primary human neutrophils have impaired movement across an endothelium deficient in APRC1B. We also show that the combined deficiency of ARPC1B in iNeutrophils and endothelium results in further reduction in neutrophil migration. Taken together, these results suggest that ARPC1B in endothelium is sufficient to drive neutrophil behavior. Furthermore, the findings provide support for using the iPSC system to understand human neutrophil biology and model disease in a genetically tractable system.

The Importance of Outcomes Ascertainment for Accurate Assessment of the Mammography Screening Cancer Detection Rate: A Simulation Study.

PURPOSE: Cancer detection rate (CDR), an important metric in the mammography screening audit, is designed to ensure adequate sensitivity. Most practices use biopsy results as the reference standard; however, commonly ascertainment of biopsy results is incomplete. We used simulation to determine the relationship between the cancer ascertainment rate of biopsy (AR-biopsy), CDR estimation, and associated error rates in classifying whether practices and radiologists meet the established ACR benchmark of 2.5 per 1,000. MATERIALS AND METHODS: We simulated screening mammography volume, number of cancers detected, and CDR, using negative binomial and beta-binomial distributions, respectively. Simulations were performed at both the practice and radiologist level. Average CDR was based on linearly rescaling a published CDR by the AR-biopsy. CDR distributions were simulated for AR-biopsy between 5% and 100% in steps of five percentage points and were summarized with boxplots and smoothed histograms over the range of AR-biopsy, to quantify the proportion of practices and radiologists meeting the ACR benchmark at each level of AR-biopsy. RESULTS: Decreasing AR-biopsy led to an increasing probability of categorizing CDR performance as being below the ACR benchmark. Our simulation predicts that at the practice level, an AR-biopsy of 65% categorizes 17.6% below the benchmark (compared to 1.6% at an AR-biopsy of 100%), and at the radiologist level, an AR-biopsy of 65% categorizes 34.7% as being below the benchmark (compared to 11.6% at an AR-biopsy of 100%). CONCLUSIONS: Our simulation demonstrates that decreasing the AR-biopsy (in currently clinically relevant ranges) has the potential to artifactually lower the assessed CDR on both the practice and radiologist levels and may, in turn, increase the chance of erroneous categorization of underperformance per the ACR benchmark.

Linking GATA2 to myeloid dysplasia and complex cytogenetics in adult myelodysplastic neoplasm and acute myeloid leukemia.

ABSTRACT: GATA binding protein 2 (GATA2) is a conserved zinc finger transcription factor that regulates the emergence and maintenance of complex genetic programs driving development and function of hematopoietic stem and progenitor cells (HSPCs). Patients born with monoallelic GATA2 mutations develop myelodysplastic neoplasm (MDS) and acute myeloid leukemia (AML), whereas acquired GATA2 mutations are reported in 3% to 5% of sporadic AML cases. The mechanisms by which aberrant GATA2 activity promotes MDS and AML are incompletely understood. Efforts to understand GATA2 in basic biology and disease will be facilitated by the development of broadly efficacious antibodies recognizing physiologic levels of GATA2 in diverse tissue types and assays. Here, we purified a polyclonal anti-GATA2 antibody and generated multiple highly specific anti-GATA2 monoclonal antibodies, optimized them for immunohistochemistry on patient bone marrow bioosy samples, and analyzed GATA2 expression in adults with healthy bone marrow, MDS, and acute leukemia. In healthy bone marrow, GATA2 was detected in mast cells, subsets of CD34+ HSPCs, E-cadherin-positive erythroid progenitors, and megakaryocytes. In MDS, GATA2 expression correlates with bone marrow blast percentage, positively correlates with myeloid dysplasia and complex cytogenetics, and is a nonindependent negative predictor of overall survival. In acute leukemia, the percent of GATA2+ blasts closely associates with myeloid lineage, whereas a subset of lymphoblastic and undifferentiated leukemias with myeloid features also express GATA2. However, the percent of GATA2+ blasts in AML is highly variable. Elevated GATA2 expression in AML blasts correlates with peripheral neutropenia and complex AML cytogenetics but, unlike in MDS, does not predict survival.

Indirect cardiac output assessment in a swine pediatric acute respiratory distress syndrome model.

PURPOSE: To investigate the correlation between volume of carbon dioxide elimination (V̇CO2) and end-tidal carbon dioxide (PETCO2) with cardiac output (CO) in a swine pediatric acute respiratory distress syndrome (ARDS) model. METHODS: Respiratory and hemodynamic variables were collected from twenty-six mechanically ventilated juvenile pigs under general anesthesia before and after inducing ARDS, using oleic acid infusion. RESULTS: Prior to ARDS induction, mean (SD) CO, V̇CO2, PETCO2, and dead space to tidal volume ratio (Vd/Vt) were 4.16 (1.10) L/min, 103.69 (18.06) ml/min, 40.72 (3.88) mmHg and 0.25 (0.09) respectively. Partial correlation coefficients between average CO, V̇CO2, and PETCO2 were 0.44 (95% confidence interval: 0.18-0.69) and 0.50 (0.18-0.74), respectively. After ARDS induction, mean CO, V̇CO2, PETCO2, and Vd/Vt were 3.33 (0.97) L/min, 113.71 (22.97) ml/min, 50.17 (9.73) mmHg and 0.40 (0.08). Partial correlations between CO and V̇CO2 was 0.01 (-0.31 to 0.37) and between CO and PETCO2 was 0.35 (-0.002 to 0.65). CONCLUSION: ARDS may limit the utility of volumetric capnography to monitor CO.

Newborn Screening for Severe Combined Immunodeficiency: Lessons Learned from Screening and Follow-Up of the Preterm Newborn Population.

Newborn screening (NBS) for Severe Combined Immunodeficiency (SCID) by measurement of T-cell receptor excision circles (TRECs) successfully identifies newborns with SCID and severe T-cell lymphopenia, as intended. At the same time, NBS programs face the challenge of false positive results, with a disproportionately high number in the premature newborn population. This study evaluates TREC values and SCID screening outcomes in premature newborns and elucidates evidence-based SCID screening practices that reduce unnecessary follow-up activities in this population. De-identified individual SCID newborn screening data and aggregate SCID screening data were obtained from seven states across the US for babies born between 2018 and 2020. Relevant statistics were performed on data pooled from these states to quantify screening performance metrics and clinical impact on various birth and gestational age categories of newborns. The data were normalized using multiples-of-the-median (MoM) values to allow for the aggregation of data across states. The aggregation of NBS data across a range of NBS programs highlighted the trajectory of TREC values over time, both between and within newborns, and provides evidence for improved SCID screening recommendations in the premature and low birth weight population.

Comparison of chest radiograph and lung ultrasound in children with acute respiratory failure.

PURPOSE: Chest x-ray (CXR) is the standard imaging used to evaluate children in acute respiratory distress and failure. Our objective was to compare the lung-imaging techniques of CXR and lung ultrasound (LUS) in the evaluation of children with acute respiratory failure (ARF) to quantify agreement and to determine which technique identified a higher frequency of pulmonary abnormalities. METHODS: This was a secondary analysis of a prospective observational study evaluating the sensitivity and specificity of LUS in children with ARF from 12/2018 to 02/2020 completed at the University of Wisconsin-Madison (USA). Children > 37.0 weeks corrected gestational age and ≤ 18 years of age admitted to the PICU with ARF were evaluated with LUS. We compared CXR and LUS completed within 6 h of each other. Kappa statistics (k) adjusted for maximum attainable agreement (k/kmax) were used to quantify agreement between imaging techniques and descriptive statistics were used to describe the frequency of abnormalities. RESULTS: Eighty-eight children had LUS completed, 32 with concomitant imaging completed within 6 h are included. There was fair agreement between LUS and CXR derived diagnoses with 58% agreement (k/kmax = 0.36). Evaluation of imaging patterns included: normal, 57% agreement (k = 0.032); interstitial pattern, 47% agreement (k = 0.003); and consolidation, 65% agreement (k = 0.29). CXR identified more imaging abnormalities than LUS. CONCLUSIONS: There is fair agreement between CXR and LUS-derived diagnoses in children with ARF. Given this, clinicians should consider the benefits and limitations of specific imaging modalities when evaluating children with ARF. Additional studies are necessary to further define the role of LUS in pediatric ARF given the small sample size of our study.

Novel autoantibodies help diagnose anti-SSA antibody negative Sjögren's disease and predict abnormal labial salivary gland pathology.

Objectives: Sj□gren's disease (SjD) diagnosis requires either positive anti-SSA antibodies or a labial salivary gland biopsy with a positive focus score (FS). One-third of SjD patients lack anti-SSA antibodies (SSA-), requiring a positive FS for diagnosis. Our objective was to identify novel autoantibodies to diagnose 'seronegative' SjD. Methods: IgG binding to a high density whole human peptidome array was quantified using sera from SSA- SjD cases and matched non-autoimmune controls. We identified the highest bound peptides using empirical Bayesian statistical filters, which we confirmed in an independent cohort comprising SSA- SjD (n=76), sicca controls without autoimmunity (n=75), and autoimmune controls (SjD features but not meeting SjD criteria; n=41). In this external validation, we used non-parametric methods for peptide abundance and controlled false discovery rate in group comparisons. For predictive modeling, we used logistic regression, model selection methods, and cross-validation to identify clinical and peptide variables that predict SSA- SjD and FS positivity. Results: IgG against a peptide from D-aminoacyl-tRNA deacylase (DTD2) was bound more in SSA- SjD than sicca controls (p=.004) and more than combined controls (sicca and autoimmune controls combined; p=0.003). IgG against peptides from retroelement silencing factor-1 (RESF1) and DTD2, were bound more in FS-positive than FS-negative participants (p=.010; p=0.012). A predictive model incorporating clinical variables showed good discrimination between SjD versus control (AUC 74%) and between FS-positive versus FS-negative (AUC 72%). Conclusion: We present novel autoantibodies in SSA- SjD that have good predictive value for SSA- SjD and FS-positivity. KEY MESSAGES: What is already known on this topic - Seronegative (anti-SSA antibody negative [SSA-]) Sjögren's disease (SjD) requires a labial salivary gland biopsy for diagnosis, which is challenging to obtain and interpret. What this study adds - We identified novel autoantibodies in SSA- SjD that, when combined with readily available clinical variables, provide good predictive ability to discriminate 1) SSA- SjD from control participants and 2) abnormal salivary gland biopsies from normal salivary gland biopsies. How this study might affect research, practice or policy - This study provides novel diagnostic antibodies addressing the critical need for improvement of SSA- SjD diagnostic tools.

Respiratory Severity Score during the First 3 Hours of Life as a Predictor for Failure of Noninvasive Respiratory Support and Need for Late Rescue Surfactant Administration.

OBJECTIVE: Preterm infants often develop failure of noninvasive respiratory support. These infants miss the advantages of early rescue surfactant therapy. In this study, we evaluate the utility of respiratory severity score (RSS) during the first 3 hours of life (HOL) as a predictor for failure of noninvasive respiratory support. STUDY DESIGN: We conducted a post hoc analysis of infants between 23 and 40 weeks' gestational age who received usual care in the AERO-02 clinical trial. Univariate and multivariable logistic regression analysis were used to assess whether the RSS summary measures were associated with the odds of surfactant administration. RESULTS: Study involved 146 infants. Sixty-four infants (45%) received surfactant within the first 72 hours. Administration of surfactant was associated with the mean RSS (p < 0.01) and the linear trend (p < 0.01). CONCLUSION: We demonstrated that RSS during the first 3 HOL can predict failure of noninvasive respiratory support and need for late rescue surfactant administration. Optimal RSS cutoffs for early rescue surfactant therapy need to be determined in large cohort studies. KEY POINTS: · Early recognition of infants at risk of failure of noninvasive ventilation is important to prevent complications.. · It is desirable to identify patients who would benefit from early rescue surfactant treatment.. · RSS in first 3 hours can be used as a predictor of failure of noninvasive respiratory support..

Risk of Hypovitaminosis and Vitamin C Deficiency in Pediatric Patients Undergoing Cardiopulmonary Bypass.

Vitamin C levels are known rapidly decrease in adult critical illness. Vitamin C scavenges free radicals, provides critical protection of the endothelial barrier, and improves endothelial responsiveness to catecholamines. Children with congenital heart disease and undergoing cardiac surgery might be at increased risk for low circulating vitamin C levels. A prospective single-center observational study investigated perioperative changes in vitamin C levels in critically ill Children who underwent congenital heart surgery using CPB. Vitamin C serum levels were collected preoperatively and postoperatively (upon admission to the ICU, 24 and 72 h). Linear mixed-effect model was used to estimate mean circulating concentration of vitamin C and to estimate changes in concentration over time. Primary outcome was change in circulating levels of vitamin C before and after CPB. Secondary outcomes were hospital length of stay (LOS), acute kidney injury (AKI), and illness severity. Forty-one patients with a median age of 4.5 [interquartile range (IQR) 2.6-65.6] months at the time of surgery were consented and enrolled. Median CPB duration was 130 [90-175] minutes, and hospital LOS was 9.1 [5.2-19] days. Mean vitamin C levels (µmol/L) before CPB, at PICU admission, 24 h, and 72 h were 82.0 (95% CI 73.4-90.7), 53.4 (95% CI 44.6,62.0), 55.1 (95% CI 46.3,63.8), and 59.2 (95% CI 50.3,68.1), respectively. Upon postoperative admission to the PICU, vitamin C levels decreased by 28.7 (95% CI 20.6-36.8; p < 0.001) µmol/L, whereas levels at 24 and 72 h recovered and did not differ substantially from concentrations reported upon PICU admission (p > 0.15). Changes in vitamin C concentration were not associated with CPB time, STAT mortality category, age, or PIM3. Three patients had post-CPB hypovitaminosis C or vitamin C deficiency. Reduction in vitamin C levels was not associated with hospital LOS (p = 0.673). A 25 µmol/L decrease in vitamin C levels upon PICU admission was associated with developing AKI (aOR = 3.65; 95% CI 1.01-18.0, p = 0.049). Pediatric patients undergoing cardiac surgery with CPB showed decreased vitamin C levels during the immediate postoperative period. Effects of hypovitaminosis C and vitamin C deficiency in this population remain unclear.

Response to aerosolized calfactant in infants with respiratory distress syndrome; a post-hoc analysis of AERO-02 trial.

BACKGROUND: The aerosolized calfactant decreased the need for intubation in neonates with respiratory distress syndrome (AERO-02 trial). OBJECTIVE: To determine the oxygenation response to aerosolized calfactant among infants born 28 0/7-36 6/7 weeks with RDS in the AERO-02 trial. METHODS: Trends in hourly fraction of oxygen (FiO2), mean airway pressure (MAP) and respiratory severity score (RSS) were compared between the aerosolized calfactant (AC) and usual care (UC) groups from time of randomization for 72 h. RESULTS: A total of 353 subjects were included in the study. FiO2, MAP, and RSS were lower in the UC group. FiO2 decrease was seen after the first aerosolized calfactant dose. CONCLUSION: FiO2, MAP, and RSS were lower in the UC group. This is likely due to early and higher rate of liquid surfactant administration in the UC group. Decrease in FiO2 was noted in the AC group after the first aerosolization.

Computed tomographic laryngotracheal dimensions in adult domestic rabbits (Oryctolagus cuniculus) are positively associated with body weight and the laryngotracheal lumen is narrowest at the level of the thyroid cartilage.

OBJECTIVE: This retrospective study aimed to measure rabbit laryngotracheal dimensions at different locations on computed tomography (CT), assess the relationship of these measurements with rabbit body weight, determine the most common narrowest measurement and assess its relationship with endotracheal tube (ETT) size and body weight. ANIMALS: 66 adult domestic rabbits (Oryctolagus cuniculus) of different breeds and body weights. PROCEDURES: CT laryngotracheal luminal height, width, and cross-sectional area measurements were made at the rostral thyroid cartilage at the level of the arytenoids, caudal thyroid cartilage/rostral cricoid cartilage, caudal cricoid cartilage/cranial trachea, and trachea at the level of the fifth cervical vertebra. RESULTS: The data for every measurement of luminal airway dimensions revealed robust positive associations with body weight (P < .001). The narrowest laryngotracheal measurement was the width at the level of the caudal thyroid cartilage/rostral cricoid cartilage, and the smallest cross-sectional area was at the rostral thyroid cartilage at the level of the arytenoids. There was a strong association between body weight and the likelihood of appropriate ETT fit. To have at least an 80% chance of appropriate ETT fit with a 2.0, 2.5, and 3.0 mm ETT, the rabbits' weight predicted by the model (lower 95% confidence limit) were at least 2.99 (2.72) kg, 5.24 (4.65) kg, and 5.80 (5.21) kg, respectively. CLINICAL RELEVANCE: The laryngotracheal lumen was narrowest at the level of the caudal thyroid cartilage in rabbits, which indicates this location may be the limiting factor in determining ETT size in rabbits.