Effects of intubation and hypoxemia on intraventricular hemorrhage in preterm infants during the first week: An observational study.

BACKGROUND: Preterm infants with intraventricular hemorrhage (IVH) are at a risk of developing neurodevelopmental disabilities. Few studies have examined the effects of oxygen saturation (SpO2) changes and intubation procedures on the risk of IVH. OBJECTIVES: We examined the effects of intubation and the rates of three thresholds of hypoxemia on the occurrence of IVH in preterm infants during their first week in the neonatal intensive care unit (NICU). METHODS: In this prospective observational cohort study, preterm infants with a gestational age (GA) of <37 weeks were included from two Level III NICUs in Taiwan. Continuous electrocardiography was used to monitor SpO2 changes, and cranial ultrasonography was used to monitor IVH. Thresholds of hypoxemia (SpO2 levels of <80 %, <85 %, and <90 %) were screened by digitally sampling data at 10-s intervals. Generalized estimating equations were used with logistic regression to analyze the effects of intubation and the rates of the three thresholds of hypoxemia on the risk of IVH during the first week after birth. RESULTS: In all preterm infants (N = 73), the mean GA was 31.55 weeks, and the mean birth weight was 1508.86 g. Intubation within 3 days of birth, duration of mechanical ventilation and oxygen use, hypoxemia rate, and maternal use of magnesium sulfate before and during delivery were significantly associated with IVH. A multivariate analysis revealed that intubation was a key factor associated with the occurrence of IVH across different thresholds of hypoxemia (p = 0.004). CONCLUSIONS: Although the rate of hypoxemia, duration of mechanical ventilation and oxygen use, and maternal use of magnesium sulfate were significantly associated with IVH, intubation within 3 days of birth was the key factor responsible for increased IVH risk.

Neurological and cardiopulmonary manifestations of pulmonary arteriovenous malformations.

Pulmonary arteriovenous malformations (PAVMs) are direct pulmonary artery-to-vein connections without pulmonary capillaries that result in intrapulmonary right-to-left blood shunts. Although most patients with PAVMs may be entirely asymptomatic, PAVMs can induce a series of complications involving the neurological, cardiovascular, and respiratory systems that can lead to catastrophic and often fatal clinical sequelae. In this study we review the available literature and summarize the reported PAVM-related complications among patients with PAVMs. The reviewed studies included observational studies, case studies, prospective studies, and cohort studies, and we provide an overview of PAVM-related neurological and cardiopulmonary manifestations, including stroke, cerebral abscess, transient ischemic attack, cerebral hemorrhage, migraine, seizure, dizziness, cardiac failure, arrhythmia, myocardial infarction, cough, hypoxemia, dyspnea, respiratory failure, hemoptysis, and hemothorax. Identifying and treating PAVMs before the presentation of major complication is important because this can prevent the occurrence of complications and can result in better outcomes. PAVM patients should thus be better evaluated and managed by a multidisciplinary team because they may be in a treatable phase prior to their condition becoming life-threatening.

Assessing Cognitive Impairments in Obstructive Sleep Apnea Patients Using Montreal Cognitive Assessment (MoCA) Scores.

Obstructive Sleep Apnea (OSA) is a chronic condition associated with cognitive impairment and various comorbidities. This prospective study evaluated cognitive deficits in OSA patients and identified clinical factors affecting cognitive function. Seventy-two participants were assessed using polysomnography (PSG) and the Montreal Cognitive Assessment (MoCA). Findings revealed significantly lower MoCA scores in severe OSA patients compared to those with mild or moderate OSA. Severe OSA patients had a median MoCA score of 23.5 (20.0-25.0), indicating more significant cognitive impairment, while those with normal OSA severity had the highest median score of 28.5 (27.8-29.2). Mild and moderate OSA patients had median scores of 26.5 (21.0-28.0) and 25.0 (23.80-26.0), respectively (p < 0.008). Logistic regression showed that ex-smoking status negatively impacted MoCA scores more in the unadjusted model (p = 0.003) than in the adjusted one (p = 0.018). Forced Vital Capacity (FVC) positively correlated with MoCA scores, stronger in the unadjusted model (p < 0.001 vs. p < 0.03). Higher Oxygen Desaturation Index (ODI) correlated with higher MoCA scores while increasing Apnea-Hypopnea Index (AHI) severity correlated with lower MoCA scores in both models. A significant negative correlation was found between age and MoCA score (r = -0.473, p < 0.001), and between MoCA score and AHI (r = -0.350, p < 0.003). This study highlights the need for sensitive cognitive screening tools like MoCA in evaluating OSA patients, linking cognitive impairment closely with OSA severity and other clinical factors.

Platypnea-Orthodeoxia Syndrome: Presentation of a 90-Year-Old.

Platypnea-orthodeoxia syndrome (POS) is a clinical syndrome of dyspnea and hypoxemia that is exacerbated by sitting upright or standing and resolved with lying flat. Here, we discuss an initial presentation of POS as a result of a previously undiagnosed patent foramen ovale (PFO) in a 90-year-old man. Diagnosis of the PFO was limited by technically difficult transthoracic echocardiograms with inconclusive agitated saline studies. Transesophageal echocardiogram (TEE) with Doppler and agitated saline study was eventually diagnostic, and his symptoms resolved after percutaneous PFO closure. The diagnosis and treatment in this patient were complicated by his age, moderate dementia, and limited decision-making capacity. Although our patient was dependent for virtually all instrumental activities of daily living (iADLs), he and his family reported an excellent quality of life prior to presentation, and we anticipated he would be able to regain this post-procedurally, allowing us to advocate for TEE and subsequent PFO repair. In the geriatric population, special consideration must be taken to discuss the risks and benefits of extensive workup and treatment depending on the effectiveness and invasiveness of both; approaching these cases with this holistic approach can thus help guide their clinical course appropriately.

Hemoglobin J-Auckland: a clinically silent low oxygen affinity variant presenting with persistent asymptomatic hypoxemia at high altitude.

BACKGROUND: Inherited hemoglobin disorders are common in clinical practice. While qualitative (i.e. sickle cell disease) and quantitative (thalassemia) hemoglobinopathies are usually diagnosed clinically and confirmed through simple laboratory assessments, hemoglobin variants with altered oxygen affinity often go undetected due to their typically silent clinical presentation. Hemoglobin (Hb) J-Auckland, a low oxygen affinity hemoglobin variant first described in 1987 in Auckland, New Zealand, is one such silent disorder. CASE PRESENTATION: We report for the first time a clinically evident case of previously undiagnosed Hb J-Auckland in an 8-year-old girl who presented with unexplained hypoxemia at high altitude. Her oxygen level was corrected with supplemental oxygen and when assessed at low altitude. A brief discussion of the diagnostic approach and clinical implications is provided. CONCLUSION: Standard hemoglobin analysis is essential for the evaluation of suspected altered affinity hemoglobinopathy, and genetic testing is often required for definitive diagnosis. Early recognition and diagnosis of these variants can prevent mismanagement and improve patient outcomes.

Closed-loop oxygen usage during invasive mechanical ventilation of pediatric patients (CLOUDIMPP): a randomized controlled cross-over study.

Background: The aim of this study is the evaluation of a closed-loop oxygen control system in pediatric patients undergoing invasive mechanical ventilation (IMV). Methods: Cross-over, multicenter, randomized, single-blind clinical trial. Patients between the ages of 1 month and 18 years who were undergoing IMV therapy for acute hypoxemic respiratory failure (AHRF) were assigned at random to either begin with a 2-hour period of closed-loop oxygen control or manual oxygen titrations. By using closed-loop oxygen control, the patients' SpO2 levels were maintained within a predetermined target range by the automated adjustment of the FiO2. During the manual oxygen titration phase of the trial, healthcare professionals at the bedside made manual changes to the FiO2, while maintaining the same target range for SpO2. Following either period, the patient transitioned to the alternative therapy. The outcomes were the percentage of time spent in predefined SpO2 ranges ±2% (primary), FiO2, total oxygen use, and the number of manual adjustments. Findings: The median age of included 33 patients was 17 (13-55.5) months. In contrast to manual oxygen titrations, patients spent a greater proportion of time within a predefined optimal SpO2 range when the closed-loop oxygen controller was enabled (95.7% [IQR 92.1-100%] vs. 65.6% [IQR 41.6-82.5%]), mean difference 33.4% [95%-CI 24.5-42%]; P < 0.001). Median FiO2 was lower (32.1% [IQR 23.9-54.1%] vs. 40.6% [IQR 31.1-62.8%]; P < 0.001) similar to total oxygen use (19.8 L/h [IQR 4.6-64.8] vs. 39.4 L/h [IQR 16.8-79]; P < 0.001); however, median SpO2/FiO2 was higher (329.4 [IQR 180-411.1] vs. 246.7 [IQR 151.1-320.5]; P < 0.001) with closed-loop oxygen control. With closed-loop oxygen control, the median number of manual adjustments reduced (0.0 [IQR 0.0-0.0] vs. 1 [IQR 0.0-2.2]; P < 0.001). Conclusion: Closed-loop oxygen control enhances oxygen therapy in pediatric patients undergoing IMV for AHRF, potentially leading to more efficient utilization of oxygen. This technology also decreases the necessity for manual adjustments, which could reduce the workloads of healthcare providers. Clinical Trial Registration: This research has been submitted to ClinicalTrials.gov (NCT05714527).

Long-term oxygen therapy in precapillary pulmonary hypertension - SOPHA study.

Current guidelines recommend oxygen (O2) supplementation in patients with pulmonary hypertension (PH), despite scarce data on long-term O2 therapy (LTOT). The aim of this prospective, randomized, controlled trial was to investigate the effect of LTOT in patients with precapillary PH on exercise capacity, clinical parameters and hemodynamics. Patients with precapillary PH under stable therapy and O2 desaturations at rest and/or during exercise were randomized to receive LTOT (≥ 16 h/day) or no O2 (control group) for 12 weeks. The control group was offered LTOT after 12 weeks. The primary endpoint changes of 6-minute walking distance (6MWD) from baseline to 12 weeks was hierarchically tested: (1) pre-post primary and secondary intervention (2) intervention vs. control group. Secondary endpoints included changes in clinical parameters. Twenty patients were randomized (women n = 14, age 67 ± 11.4 years, mean pulmonary arterial pressure 39.7 ± 12.5 mmHg, 70% functional class III). 6MWD significantly improved by 42.2 ± 34.20 m (p = 0.003) within 12 weeks LTOT. The intervention group significantly improved in 6MWD (38.9 ± 33.87 m) compared to the control group (- 12.3 ± 21.83 m, p = 0.015). No consistent between-group differences in other parameters were found. LTOT was well tolerated and led to significant improvement of 6MWD. The effect of LTOT should be investigated in larger controlled-trials.

SLEEP APNEA IS A COMMON AND DANGEROUS CARDIOVASCULAR RISK FACTOR.

Sleep apnea involves almost one billion individuals throughout the world, including 40 million Americans. Of major medical concern is the fact that the prevalence of sleep apnea is significantly increasing due to the epidemic of obesity, physical inactivity, and diabetes mellitus which are important risk factors for the development and persistence of sleep apnea in individuals. Sleep apnea is characterized by multiple episodes of apnea or hypopnea during sleep, which cause nocturnal arousals, gasping for breath during the night, daytime sleepiness, irritability, forgetfulness, fatigue and recurrent headaches. Obstructive sleep apnea occurs when upper airway obstruction occurs in an individual during sleep with absent or markedly reduced airflow in the presence of continued activity of inspiratory thoracic and diaphragmatic muscles. Central sleep apnea is defined as the absence or the significant reduction of naso-oral airflow due to the withdrawal during sleep of ponto-medullary respiratory center stimulation of the nerves of the inspiratory thoracic and diaphragmatic muscles and absence of contraction of these muscles during apnea. Complex sleep apnea occurs when an individual exhibits characteristics of both obstructive and central sleep apnea. The severity of sleep apnea is measured by polysomnography and the apnea hypopnea index (AHI), which is the average number of apneas and hypopneas per hour of sleep measured by polysomnography. Sleep apnea is mild if the AHI is 5-14/hour with no or mild symptoms, moderate if the AHI is 15 to 30/hour with occasional daytime sleepiness, and severe if the AHI is >30/hour with frequent daytime sleepiness that interferes with the normal activities of daily life. Chronic sleep apneas and hypopneas followed by compensatory hyperpneas are associated with significant adverse cardiovascular consequences including: 1) recurrent hypoxemia and hypercarbia; 2) Increased sympathetic nerve activity and decreased parasympathetic nerve activity; 3) oxidative stress and vascular endothelial dysfunction; and 4) cardiac remodeling and cardiovascular disease. Moderate or severe sleep apnea significantly increases the risk of coronary artery disease, congestive heart failure, cerebral vascular events (strokes), and cardiac dysrhythmias, and also increase the morbidity and mortality of these diseases. Nevertheless, sleep apnea is currently underdiagnosed and untreated in many individuals due to the challenges in the prediction and detection of sleep apnea and a lack of well-defined optimal treatment guidelines. Chronic continuous positive airway pressure for ≥4 hours/night for >70% of nights is beneficial in the treatment of patients with sleep apnea. CPAP Improves sleep quality, reduces the AHI, augments cardiac output and increases oxygen delivery to brain and heart, reduces resistant hypertension, decreases cardiac dysrhythmias, and reduces daytime sleepiness. The present article discusses the diagnosis of obstructive sleep apnea, central sleep apnea, and complex apnea. Thereafter the important pathophysiologic mechanisms in sleep apnea and the relationship of these pathophysiologic mechanics to atherosclerotic vascular disease are reviewed. Guidelines are then provided for the treatment of mild, moderate and severe sleep apnea In order to reduce the cardiovascular morbidity and mortality caused by sleep apnea and facilitate the diagnosis and the long-term, effective treatment of sleep apnea in patients, the close cooperation is necessary of cardiovascular specialists, pulmonary specialists, and respiratory therapy/ rehabilitation specialists.

Pediatric COVID-19 in Lesotho and Post-pandemic Implications on Lower Respiratory Infections in Children.

Background The United States Agency for International Development (USAID) Reaching Impact, Saturation, and Epidemic Control (RISE) program funded Jhpiego to support the Government of Lesotho's COVID-19 response, including two national COVID-19 treatment centers. To evaluate the status of post-pandemic pediatric respiratory care in Lesotho, we analyzed pediatric treatment center data and healthcare worker (HCW) performance on pediatric COVID-19 training offered to HCWs at COVID-19 treatment centers. Methods We conducted a retrospective cohort study of patients 15 years of age or less hospitalized at two COVID-19 treatment centers in Lesotho from May 1, 2020, to April 30, 2022. Patient data were extracted from hospital files. We used the independent sample t-test, Mann-Whitney U test, or Fisher's exact test to evaluate associations between exposure variables and death. We also assessed differences between pre- and post-training examination scores of three one-day HCW training on pediatric COVID-19 using paired t-tests. Results Overall, <15-year-olds comprised 18/1,448 (1.2%) hospitalizations. Twenty-two percent (4/18) of children were hypoxemic (oxyhemoglobin saturation <94%) within the first 24 hours and 44% (8/18) at any point in the hospitalization. Oxygen utilization increased over the two-year period (p=0.004) and all eight children with hypoxemia received oxygen (p<0.001). Four of 18 (22%) patients died. For HCW training, pre- and post-training examinations were completed by 76/82 (92.7%) participants. The overall mean pretraining score was 44.6% (standard deviation (SD) 15.7%). Mean scores improved by an average of 32.2% (95% confidence interval (CI) 27.7%, 36.6%, p<0.001) on the same day post-training examination. Conclusions National COVID-19 treatment center data indicate a low burden of severe pediatric COVID-19 disease in Lesotho. However, recognized HCW knowledge gaps suggest deficiencies in identifying and referring severely ill children, which may detrimentally impact the ongoing post-pandemic care of children with severe lower respiratory infections.

High altitude polycythemia and its maladaptive mechanisms: an updated review.

High altitude polycythemia is a maladaptation of highlanders exposed to hypoxic environment, leading to high blood viscosity and severe cardiorespiratory dysfunction. Prolonged hypoxia causes respiratory depression and severe hypoxemia, and further mediates changes in genetic and molecular mechanisms that regulate erythropoiesis and apoptosis, ultimately resulting in excessive erythrocytosis (EE). This updated review investigated the maladaptive mechanisms of EE, including respiratory chemoreceptor passivation, sleep-related breathing disorders, sex hormones, iron metabolism, and hypoxia-related factors and pathways.

Author Response: Oxygen Delivery Devices in Postoperative Patients: Proper Selection of Patients Matters!

How to cite this article: Mishra S, Kothari N, Sharma A, Goyal S. Author Response: Oxygen Delivery Devices in Postoperative Patients: Proper Selection of Patients Matters! Indian J Crit Care Med 2024;28(8):803.

Effect of perioperative sigh ventilation on postoperative hypoxemia and pulmonary complications after on-pump cardiac surgery (E-SIGHT): study protocol for a randomized controlled trial.

BACKGROUND: Postoperative hypoxemia and pulmonary complications remain a frequent event after on-pump cardiac surgery and mostly characterized by pulmonary atelectasis. Surfactant dysfunction or hyposecretion happens prior to atelectasis formation, and sigh represents the strongest stimulus for surfactant secretion. The role of sigh breaths added to conventional lung protective ventilation in reducing postoperative hypoxemia and pulmonary complications among cardiac surgery is unknown. METHODS: The perioperative sigh ventilation in cardiac surgery (E-SIGHT) trial is a single-center, two-arm, randomized controlled trial. In total, 192 patients scheduled for elective cardiac surgery with cardiopulmonary bypass (CPB) and aortic cross-clamp will be randomized into one of the two treatment arms. In the experimental group, besides conventional lung protective ventilation, sigh volumes producing plateau pressures of 35 cmH2O (or 40 cmH2O for patients with body mass index > 35 kg/m2) delivered once every 6 min from intubation to extubation. In the control group, conventional lung protective ventilation without preplanned recruitment maneuvers is used. Lung protective ventilation (LPV) consists of low tidal volumes (6-8 mL/kg of predicted body weight) and positive end-expiratory pressure (PEEP) setting according to low PEEP/FiO2 table for acute respiratory distress syndrome (ARDS). The primary endpoint is time-weighted average SpO2/FiO2 ratio during the initial post-extubation hour. Main secondary endpoint is the severity of postoperative pulmonary complications (PPCs) computed by postoperative day 7. DISCUSSION: The E-SIGHT trial will be the first randomized controlled trial to evaluate the impact of perioperative sigh ventilation on the postoperative outcomes after on-pump cardiac surgery. The trial will introduce and assess a novel perioperative ventilation approach to mitigate the risk of postoperative hypoxemia and PPCs in patients undergoing cardiac surgery. Also provide the basis for a future larger trial aiming at verifying the impact of sigh ventilation on postoperative pulmonary complications. TRIAL REGISTRATION: ClinicalTrials.gov NCT06248320. Registered on January 30, 2024. Last updated February 26, 2024.

Can I Discharge This Adult Patient with Abnormal Vital Signs From the Emergency Department?

BACKGROUND: Vital signs are an essential component of the emergency department (ED) assessment. Vital sign abnormalities are associated with adverse events in the ED setting and may indicate a risk of poor outcomes after ED discharge. CLINICAL QUESTION: What is the risk of adverse events among adult patients with abnormal vital signs at the time of ED discharge? EVIDENCE REVIEW: Studies retrieved included 6 retrospective studies with adult patients discharged from the ED. These studies evaluated adverse outcomes in adult patients discharged from the ED with abnormal vital signs. Hypotension at discharge was associated with the highest odds of adverse events after discharge. Tachycardia was also a key predictor of adverse events after discharge and may be easily missed by ED clinicians. CONCLUSION: Based on the available evidence, the specific vital sign abnormality and the number of total abnormalities influence the risk of adverse outcomes after discharge. Vital sign abnormalities at the time of discharge also increase the risk of ED revisit. The most common abnormal vital sign at the time of discharge is tachycardia.

Temporal link between cardiac arrhythmias and postoperative episodes of hypoxemia during nocturnal sleep in patients with obstructive sleep apnea syndrome.

OBJECTIVE: Obstructive Sleep Apnea (OSA) is known to impact morbidity in the perioperative period through a postoperative exacerbation of respiratory events after general anesthesia. Cardiac arrhythmias may be triggered by respiratory and/or hypoxic events, therefore we searched for a temporal link between cardiac arrhythmias and episodes of hypoxemia following surgery under general anesthesia during the nocturnal sleep phase. METHODS: We included patients with a preoperative STOP-BANG questionnaire score between 3 and 8, planned for an elective surgery with general anesthesia. Patients had a preoperative sleep study (N0) and two postoperative sleep studies on the first (N1) and third (N3) night after surgery. Patients with mild-to-moderate OSA (apnea/hypopnea index (AHI) between 15 and 30) were compared to patients with an AHI <15 (nil-mild OSA group). Analysis was conducted to detect concomitant hypoxic episodes and cardiac arrhythmias as defined by auricular or ventricular premature complexes, ventricular or supraventricular arrhythmias. MAIN RESULTS: 39 patients comprised the moderate-OSA group and 12 patients the nil-mild OSA group. In the whole cohort, the incidence of cardiac arrhythmias associated with hypoxic episodes was increased at N3 compared to N0 (median: 1 event per hour of recorded time [IQR: 0; 4] vs 0 [0; 2], p = 0.04). We observed this in the OSA group compared to the nil-mild OSA group (1 [0; 4] vs 1 [0; 2], respectively; p = 0.02). CONCLUSION: This study indicates that more cardiac arrhythmias associated with hypoxemic episodes can be observed in the postoperative night, in patients with moderate OSA. This reinforces the importance of preoperative screening for OSA. CLINICAL TRIAL REGISTRY: NCT02833662.

Usefulness of deep sedation with intravenous dexmedetomidine and midazolam in cardiac catheterization procedures for pediatric patients.

Background: Dexmedetomidine (DEX) is a highly selective alpha 2 receptor agonist that has the advantage of causing less respiratory depression than other sedative agents. We evaluated the add-on effects of DEX on sedation among pediatric patients who received midazolam and pentazocine during cardiac catheterization. Methods: 120 cardiac catheterization procedures in 110 patients under deep sedation at Department of Pediatrics, Kanazawa University Hospital from January 2013 to August 2018: 63 procedures without DEX (i.e., non-DEX group) and 57 procedures with DEX (i.e., DEX group). Intravenous midazolam and pentazocine were used in both groups, and DEX without an initial loading dose (0.6 µg/kg/h) was used in the DEX group. We retrospectively investigated complications during catheterization, doses of sedative agents, and changes in vital signs. Results: Hypoxemia requiring oxygen administration during catheterization tended to be higher in the non-DEX group than in the DEX group (4.8% vs. 0%). Additional dose of midazolam was significantly lower in the DEX group (median [IQR]: 0.05 mg/kg [0-0.11]) than in the non-DEX group [0.09 mg/kg (0-0.23), p = 0.0288]. The additional dose of midazolam in the non-DEX group with hypoxemia was significantly higher than the dose used in the non-DEX group without hypoxemia. No case of bradycardia below the criteria for bradycardia occurred and no serious complications occurred in the DEX group. Conclusion: The use of intravenous DEX in combination with midazolam and pentazocine in pediatric cardiac catheterization may reduce the need for an additional dose of midazolam and may contribute to the prevention of airway complications associated with respiratory depression caused by sedative agents.

Exploring the bias: how skin color influences oxygen saturation readings via Monte Carlo simulations.

Significance: Our goal is to understand the root cause of reported oxygen saturation ( SpO 2 ) overestimation in heavily pigmented skin types to devise solutions toward enabling equity in pulse oximeter designs. Aim: We aim to gain theoretical insights into the effect of skin tone on SpO 2 - R curves using a three-dimensional, four-layer tissue model representing a finger. Approach: A finger tissue model, comprising the epidermis, dermis, two arteries, and a bone, was developed using a Monte Carlo-based approach in the MCmatlab software. Two skin tones-light and dark-were simulated by adjusting the absorption and scattering properties within the epidermal layer. Following this, SpO 2 - R curves were generated in various tissue configurations, including transmission and reflection modes using red and infrared wavelengths. In addition, the influence of source-detector (SD) separation distances on both light and dark skin tissue models was studied. Results: In transmission mode, SpO 2 - R curves did not deviate with changes in skin tones because both pulsatile and non-pulsatile terms experienced equal attenuation at red and infrared wavelengths. However, in reflection mode, measurable variations in SpO 2 - R curves were evident. This was due to differential attenuation of the red components, which resulted in a lower perfusion index at the red wavelength in darker skin. As the SD separation increased, the effect of skin tone on SpO 2 - R curves in reflection mode became less pronounced, with the largest SD separation exhibiting effects similar to those observed in transmission mode. Conclusions: Monte Carlo simulations have demonstrated that different light pathlengths within the tissue contribute to the overestimation of SpO 2 in people with darker skin in reflection mode pulse oximetry. Increasing the SD separation may mitigate the effect of skin tone on SpO 2 readings. These trends were not observed in transmission mode; however, further planned research using more complex models of the tissue is essential.

Multimodal analysis of dysregulated heme metabolism, hypoxic signaling, and stress erythropoiesis in Down syndrome.

Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), is characterized by delayed neurodevelopment, accelerated aging, and increased risk of many co-occurring conditions. Hypoxemia and dysregulated hematopoiesis have been documented in DS, but the underlying mechanisms and clinical consequences remain ill defined. We report an integrative multi-omic analysis of ∼400 research participants showing that people with DS display transcriptomic signatures indicative of elevated heme metabolism and increased hypoxic signaling across the lifespan, along with chronic overproduction of erythropoietin, elevated biomarkers of tissue-specific hypoxia, and hallmarks of stress erythropoiesis. Elevated heme metabolism, transcriptional signatures of hypoxia, and stress erythropoiesis are conserved in a mouse model of DS and associated with overexpression of select triplicated genes. These alterations are independent of the hyperactive interferon signaling characteristic of DS. These results reveal lifelong dysregulation of key oxygen-related processes that could contribute to the developmental and clinical hallmarks of DS.