Hypoxia Index Research Articles

Prevention of Intrapartum Brain Damage with Hypoxia Index and the Problem in Preterm Birth

Prevention of Intrapartum Brain Damage with Hypoxia Index and the Problem in Preterm Birth

Objective Numeric Fetal Monitoring without FHR Pattern Classification

Objective and numeric decision was inytroduced into computerized FHR Diagnosis including FHR score, hypoxia index, actocardiographic A/B ratio and frequency spectrum analysis, where computerized FHR analysis made it possible to satisfactory predet fetal outcome, where the system composed of these diagnostic tools, which directory reported the results attendant doctor improving perinatal outcome.

Possible Reduction of Cerebral Palsy with Novel Strategies

Intrapartum brain damage followed by cerebral palsy developed after the loss of fetal heart rate variability and new hypoxia index was 25 or more, thus, early delivery will be done before these CP predictive borders in fetal monitoring. Very early sign of uterine contraction should be detected to cease preterm labor reducing neurological sequels. Neonatal brain PVE should be rejected after preterm birth reducing PVL and CP. The respiratory distress syndrome is predicted for 96% by ultrasonic GLHW fetal lung tissue characterization, reducing hypoxic neonatal disorder of central nervous system.

The specificity of color Doppler ultrasound to detect fetal hypoxia in pregnancy-induced-hypertension with thyroid dysfunction

The incidence of fetal hypoxia in pregnant women with Pregnancy-Induced Hypertension (PIH) is higher than normal pregnant women. Thyroid hormone is closely related to organism’s metabolism. In this study, Color Doppler ultrasound was used to diagnose fetal hypoxia in pregnant women with PIH to further explore the correlation of hemodynamic indexes and thyroid hormone levels. 70 cases of pregnant women with PIH were divided into thyroid-normal group (39 cases), hyperthyroidism group (12 cases) and hypothyroidism group (19 cases). The hemodynamic indexes of Middle Cerebral Artery (MCA) and Umbilical Artery (UA) were detected by color Doppler ultrasound. In hyperthyroidism and hypothyroidism groups, the hemodynamic indexes of MCA were lower and hemodynamic indexes of UA were higher than thyroid-normal group. The results of correlation tests showed that, the hemodynamic indexes of UA and fetal hypoxia were both significantly correlated to thyroid hormone levels respectively, in pregnant women with PIH. Therefore, the hemodynamic index of UA may be an index which can predict thyroid function status in pregnant women with PIH. Pregnant women with PIH and thyroid dysfunction are more likely to get fetal hypoxia than those with normal thyroid function. Color Doppler ultrasound is sensitive to detect the changes.

Importance of Hypoxia Index in FHR Monitoring

Importance of Hypoxia Index in FHR Monitoring

Assessment of sleep-disordered breathing using hypoxia index

Objective: To analyze the clinical significance of hypoxia index (HI) in assessing the severity of hypoxemia in obstructive sleep apnoea hypopnea syndrome(OSAHS). Methods: A total of 127 patients with a complaint of snoring visiting our hospital were recruited from February 2014 to January 2016. All patients received polysomnography (PSG) test. The PSG results were analyzed by a technician and the SpO(2) data were analyzed by a pre-designed computer software. The patients were grouped according to apnea hypopnea index (AHI) and lowest oxygen saturation (LSpO(2)) respectively. Receiver operating characteristic (ROC) curve was used to evaluate the best HI diagnostic value. Results: The HI (median) of the simple snoring, mild, moderate and severe OSAHS groups (according to AHI) were 0.027(0.004, 0.554), 0.281(0.045, 0.353), 0.429(0.099, 1.677), 21.714(2.737, 95.473), respectively. There were statistically significant correlation between HI and AHI, LSpO(2), ≥3% oxygen desaturation index(ODI(3)), the correlation coefficient being 0.78, -0.92, 0.87(U value were 8.76, -10.34, 9.72, all P<0.01). Grouped according to LSpO(2), the HI was significantly different between groups (H value were 7.62-14.39, all P<0.05). Conclusion: If the HI diagnostic value was set reasonably, it might be used as an effective index for evaluating the severity of OSAHS.

Maternal nutrient restriction in guinea pigs leads to fetal growth restriction with evidence for chronic hypoxia.

BackgroundWe determined whether maternal nutrient restriction (MNR) in guinea pigs leading to fetal growth restriction (FGR) impacts markers for tissue hypoxia, implicating a mechanistic role for chronic hypoxia.MethodsGuinea pigs were fed ad libitum (Control) or 70% of the control diet before pregnancy, switching to 90% at mid-pregnancy (MNR). Near term, hypoxyprobe-1 (HP-1), a marker of tissue hypoxia, was injected into pregnant sows. Fetuses were then necropsied and liver, kidney, and placental tissues were processed for erythropoietin (EPO), EPO-receptor (EPOR), and vascular endothelial growth factor (VEGF) protein levels, and for HP-1 immunoreactivity (IR).ResultsFGR-MNR fetuses were 36% smaller with asymmetrical growth restriction compared to controls. EPO and VEGF protein levels were increased in the female FGR-MNR fetuses, providing support for hypoxic stimulus and linkage to increased erythropoiesis, but not in the male FGR-MNR fetuses, possibly reflecting a weaker link between oxygenation and erythropoiesis. HP-1 IR was increased in the liver and kidneys of both male and female FGR-MNR fetuses as an index of local tissue hypoxia, but with no changes in the placenta.ConclusionChronic hypoxia is likely to be an important signaling mechanism for the decreased fetal growth seen with maternal undernutrition and appears to be post-placental in nature.

The development of late FHR deceleration and analysis of controversy FHR with hypoxia index.

Controversy late deceleration of FHR of favorable neonatal outcome was analyzed by the developing mechanism of abnormal FHR changes and hypoxia index determined with the sum of deceleration duration and nadir heart rate.

Hypoxia index precisely covers the roles of FHR deceleration and bradycardia in fetal monitoring

Hypoxia index precisely covers the roles of FHR deceleration and bradycardia in fetal monitoring

Cord blood erythropoietin and cord blood nucleated red blood cells for prediction of adverse neonatal outcome associated with maternal obesity in term pregnancy: prospective cohort study

Objective: To determine the adverse pregnancy outcomes associated with maternal pre-pregnancy overweight and obesity and we measure cord blood erythropoietin and NRBC count as indices of hypoxia and predictors of neonatal outcome.Study design: This prospective cohort study was done in Minia University Hospital, carried out from May 2015 to April 2016. Two hundred and seventy full-term neonates born to mothers of various body mass indices were included. Excluded were neonates with major factors known to be associated with a potential increase in fetal erythropoiesis. Pre-pregnancy maternal BMI was calculated from maternally reported weight and height. Cord blood erythropoietin and nucleated red blood cells were measured.Results: There is a significant increase of various adverse pregnancy outcomes as cesarean section. Postpartum hemorrhage and macrosomia with the increase of maternal pre-pregnancy BMI. Significant positive correlations between cord blood erythropoietin and nucleated red blood cells with maternal BMI.Conclusion: The increase in the maternal pre-pregnancy BMI is associated with poor pregnancy outcomes. Cord blood erythropoietin and nucleated red blood cells can predict the poor neonatal outcome.

Hypoxia-Activated Prodrug TH-302 Targets Hypoxic Bone Marrow Niches in Preclinical Leukemia Models.

To characterize the prevalence of hypoxia in the leukemic bone marrow, its association with metabolic and transcriptional changes in the leukemic blasts and the utility of hypoxia-activated prodrug TH-302 in leukemia models. Hyperpolarized magnetic resonance spectroscopy was utilized to interrogate the pyruvate metabolism of the bone marrow in the murine acute myeloid leukemia (AML) model. Nanostring technology was used to evaluate a gene set defining a hypoxia signature in leukemic blasts and normal donors. The efficacy of the hypoxia-activated prodrug TH-302 was examined in the in vitro and in vivo leukemia models. Metabolic imaging has demonstrated increased glycolysis in the femur of leukemic mice compared with healthy control mice, suggesting metabolic reprogramming of hypoxic bone marrow niches. Primary leukemic blasts in samples from AML patients overexpressed genes defining a "hypoxia index" compared with samples from normal donors. TH-302 depleted hypoxic cells, prolonged survival of xenograft leukemia models, and reduced the leukemia stem cell pool in vivo In the aggressive FLT3/ITD MOLM-13 model, combination of TH-302 with tyrosine kinase inhibitor sorafenib had greater antileukemia effects than either drug alone. Importantly, residual leukemic bone marrow cells in a syngeneic AML model remain hypoxic after chemotherapy. In turn, administration of TH-302 following chemotherapy treatment to mice with residual disease prolonged survival, suggesting that this approach may be suitable for eliminating chemotherapy-resistant leukemia cells. These findings implicate a pathogenic role of hypoxia in leukemia maintenance and chemoresistance and demonstrate the feasibility of targeting hypoxic cells by hypoxia cytotoxins.

The impact of obstructive sleep apnea on nonalcoholic fatty liver disease in patients with severe obesity.

Obstructive sleep apnea (OSA) is common among candidates for bariatric surgery. OSA and its associated intermittent hypoxia have been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis. A large cohort of bariatric surgery patients was studied in an effort to explore the relationship between OSA severity, hypoxia, metabolic syndrome, and the severity of NAFLD. Bariatric surgery candidates who underwent both polysomnography and liver biopsy were studied. The severity of OSA as determined by the apnea-hypopnea index (AHI) and parameters of hypoxia was studied in relation to extent of abnormalities of liver histology as measured by the presence of hepatic steatosis, inflammation, and fibrosis. The study cohort included 362 patients with a mean age of 46.2 years and BMI of 49.9 kg/m(2) . On the basis of AHI, 26% of the cohort had no OSA, 32% mild OSA, 22% moderate OSA, and 20% severe OSA. For the study subjects without metabolic syndrome, positive correlations were found between OSA severity, as measured by AHI, and parameters of hypoxia, with the severity of NAFLD. OSA severity and its accompanying hypoxia are associated with the severity of NAFLD.

Photoplethysmographic Signal to Screen Sleep-Disordered Breathing in Hospitalized Heart Failure Patients: Feasibility of a Prospective Clinical Pathway

ObjectivesThe purpose of this study was to evaluate the plethysmographic signal-derived oxygen desaturation index (ODI) as an inpatient screening strategy to identify sleep-disordered breathing (SDB) in patients with congestive heart failure (CHF). BackgroundSDB is highly prevalent among patients hospitalized with CHF but is widely underdiagnosed. We evaluated overnight photoplethysmography as a possible screening strategy for hospitalized patients with CHF. MethodsConsecutively admitted heart failure patients with high clinical suspicion of SDB and ODI ≥5 were offered outpatient polysomnography (PSG), which was completed within 4 weeks of discharge. PSG was considered positive if the apnea hypoxia index (AHI) was ≥5. A Bland-Altman plot was used to assess agreement between ODI and AHI. Receiver-operator characteristics were determined for ODI ≥5 and AHI ≥5. ResultsA screening questionnaire identified 246 of 282 consecutive patients with positive symptoms for SDB. Of these patients, 105 patients were offered further evaluation and 86 had ODI ≥5 (mean ODI 17 ± 17). Among these 86 patients, 68 underwent outpatient PSG within 4 weeks of discharge. PSG showed that 64 (94%) had SDB, with a mean AHI of 28. Inpatient ODI correlated well with PSG-derived AHI. The area under the curve was 0.82 for AHI ≥5. The Bland-Altman plot revealed no major bias. Matthew’s correlation coefficient revealed that the optimal cut-off for ODI is 5. ConclusionsScreening hospitalized patients with heart failure using targeted inpatient ODI identifies a cohort of patients with a high prevalence of SDB. Our screening strategy provides a potentially cost-effective method for early detection and treatment of SDB.

Age, Body Mass Index, and Daytime and Nocturnal Hypoxia as Predictors of Hypertension in Patients With Obstructive Sleep Apnea.

A growing body of evidence links obstructive sleep apnea (OSA) with hypertension. The authors performed a retrospective cohort study using the University Hospital of Larissa Sleep Apnea Database (1501 patients) to determine predictors of in-laboratory diagnosed OSA for development of hypertension. Differences in continuous variables were assessed via independent samples t test, whereas discrete variables were compared by Pearson's chi-square test. Multivariate analysis was performed via discriminant function analysis. There were several significant differences between hypertensive and normotensive patients. Age, body mass index, comorbidity, daytime oxygen saturation, and indices of hypoxia during sleep were deemed the most accurate predictors of hypertension, whereas apnea-hypopnea index and desaturation index were not. The single derived discriminant function was statistically significant (Wilk's lambda=0.771, χ(2) =289.070, P<.0001). Daytime and nocturnal hypoxia as consequences of chronic intermittent hypoxia play a central role in OSA-related hypertension and should be further evaluated as possible severity markers in OSA.

Infarct location and sleep apnea: evaluating the potential association in acute ischemic stroke

BackgroundThe literature about the relationship between obstructive sleep apnea (OSA) and stroke location is conflicting with some studies finding an association and others demonstrating no relationship. Among acute ischemic stroke patients, we sought to examine the relationship between stroke location and the prevalence of OSA; OSA severity based on apnea–hypopnea index (AHI), arousal frequency, and measure of hypoxia; and number of central and obstructive respiratory events. MethodsData were obtained from patients who participated in a randomized controlled trial (NCT01446913) that evaluated the effectiveness of a strategy of diagnosing and treating OSA among patients with acute ischemic stroke and transient ischemic attack. Stroke location was classified by brain imaging reports into subdivisions of lobes, subcortical areas, brainstem, cerebellum, and vascular territory. The association between acute stroke location and polysomnographic findings was evaluated using logistic regression for OSA presence and negative binomial regression for AHI. ResultsAmong 73 patients with complete polysomnography and stroke location data, 58 (79%) had OSA. In unadjusted models, no stroke location variable was associated with the prevalence or severity of OSA. Similarly, in multivariable modeling, groupings of stroke location were also not associated with OSA presence. ConclusionsThese results indicate that OSA is present in the majority of stroke patients and imply that stroke location cannot be used to identify a group with higher risk of OSA. The results also suggest that OSA likely predated the stroke. Given this high overall prevalence, strong consideration should be given to obtaining polysomnography for all ischemic stroke patients.

Systemic inflammation up-regulates serum hepcidin in exacerbations and stabile chronic obstructive pulmonary disease

ObjectivesHepcidin is the main regulator of systemic iron homeostasis and its expression is modulated by iron status, hypoxia, erythroid factors and inflammation. The aim of our study was to examine a relationship between level of hepcidin and iron status, erythropoietic activity, hypoxia and inflammation in exacerbations and stable COPD patients. We hypothesized that hepcidin concentration is changed in COPD patients and is substantially influenced by inflammation and/or hypoxia. Design and methodsThe study included 40 COPD patients and 30 healthy subjects. We measured haemoglobin, serum level of hepcidin and parameters indicative for inflammation: interleukin-6 (IL-6) and C reactive protein (CRP); hypoxia: partial oxygen pressure and haemoglobin oxygen saturation; iron status: iron, total iron binding capacity (TIBC), transferring saturation and ferritin; and erythropoietic activity: soluble transferrin receptors, reticulocytes, and erythropoietin. ResultsHepcidin was elevated in exacerbations and in a stable phase compared to the control group and we found positive correlations of hepcidin with inflammatory markers IL-6 and CRP. Hepcidin also correlated positively with ferritin and inversely with TIBC. However, in COPD patients reticulocyte count was significantly reduced and negative correlation with hepcidin was established in exacerbation. No correlations were observed with iron, or indices of hypoxia. In the control group, positive associations were observed only with indices of iron status, positive with ferritin and negative one with TIBC. ConclusionSystemic inflammation and elevated values of IL-6 present in exacerbations and stabile COPD might be responsible for the observed increased hepcidin level.

Abstract P4-08-02: PAPAyA – The genome informatics framework for oncology applications and other clinical domains

Abstract Background: Genomics is expected to transform oncology clinical practice. However, converting genomic data into clinically actionable information is a daunting task. Genomic high-throughput technologies produce massive amounts of raw data, and its complexity presents a formidable challenge for clinical adoption. While algorithms exist to convert genomic data into meaningful biological information, they are geared towards the bioinformatics expert user, lack clinical annotation and interpretation, and are not addressing the needs of clinical experts. Furthermore, the main problem is that sequencing results should not be treated like a test as they are geared towards precision diagnostics which require patient clinical data. Methods: We present PAPAyA, a genome informatics platform that provides an overall solution to the genomic data overload which includes analysis of whole transcriptome and exome data, secure storage and management of this data and the interactive presentation of patient genome information in a contextualized manner. It is a continuum of analytics and user experiences with deep understanding of the clinical questions and the workflow. PAPAyA is a framework for hosting multiple genome informatics applications that bring information that is Connected, Digital and in Real Time. Connected in many dimensions - across hospital systems, across time, across many hospitals and their affiliates. Digital means retrievable (without complicated SQL queries) not just stored bits across modalities (genomics is a single vertical that pulls other information towards precise treatment). Real time means up to date ACTGs get converted into actionable information fast, and get to the right clinical expert without manual actions and printing reports. The framework sits on top of a digital health platform that offers core capabilities such as: persisting data and provisioning service (elastic computing), security, auditing, business workflow engine, reports service, user management service, patient identity service, provider registry service. At its core, PAPAyA provides full pipelines that analyze genomic high-throughput data, and further extract and prioritize clinically-meaningful information from the patient's genome. Furthermore, PAPAyA enables storage and secure management of this complex data which allows clinicians to query the data in a clinical action-oriented framework, as opposed to data aggregation and reporting framework. Results: We demonstrate the usability of PAPAyA using public data from TCGA breast cancer cohort. We show the utility of executing in-silico assays applied on RNAseq data, such as ER/PR/Her2, differential expression of long-noncoding RNAs, gene fusions, subtyping, hypoxia index, and other known signatures from the biomedical literature. In parallel, we annotate full exomes in order to find clinically relevant information for variants of unknown significance as well as variants with known disease and response phenotype using biological, functional, and clinical annotation resources. Conclusion: We have implemented an automated open learning system for processing genomic data to aid in clinical decision making. We already started the pilot phase and clinical evaluation with key academic collaborators. Citation Format: Nilanjana Banerjee, Konstantin Volyanskyy, Vartika Agrawal, Yong Mao, Yee-Him Cheung, Sitharthan Kamalakaran, Laurens Boekhorst, Arjan Claassen, Nevenka Dimitrova. PAPAyA – The genome informatics framework for oncology applications and other clinical domains [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-08-02.

Uterine artery blood flow, fetal hypoxia and fetal growth.

Evolutionary trade-offs required for bipedalism and brain expansion influence the pregnancy rise in uterine artery (UtA) blood flow and, in turn, reproductive success. We consider the importance of UtA blood flow by reviewing its determinants and presenting data from 191 normotensive (normal, n = 125) or hypertensive (preeclampsia (PE) or gestational hypertension (GH), n = 29) Andean residents of very high (4100-4300 m) or low altitude (400 m, n = 37). Prior studies show that UtA blood flow is reduced in pregnancies with intrauterine growth restriction (IUGR) but whether the IUGR is due to resultant fetal hypoxia is unclear. We found higher UtA blood flow and Doppler indices of fetal hypoxia in normotensive women at high versus low altitude but similar fetal growth. UtA blood flow was markedly lower in early-onset PE versus normal high-altitude women, and their fetuses more hypoxic as indicated by lower fetal heart rate, Doppler indices and greater IUGR. We concluded that, despite greater fetal hypoxia, fetal growth was well defended by higher UtA blood flows in normal Andeans at high altitude but when compounded by lower UtA blood flow in early-onset PE, exaggerated fetal hypoxia caused the fetus to respond by decreasing cardiac output and redistributing blood flow to help maintain brain development at the expense of growth elsewhere. We speculate that UtA blood flow is not only an important supply line but also a trigger for stimulating the metabolic and other processes regulating feto-placental metabolism and growth. Studies using the natural laboratory of high altitude are valuable for identifying the physiological and genetic mechanisms involved in human reproductive success.

Discordance in fetal biometry and Doppler are independent predictors of the risk of perinatal loss in twin pregnancies

Impaired fetal growth might be better evaluated in twin pregnancies by assessing the intertwin discordance rather than the individual fetal size. The aim of this study was to investigate the prediction of perinatal loss in twin pregnancy using discordance in fetal biometry and Doppler. This was a retrospective cohort study in a tertiary referral center. The estimated fetal weight (EFW), umbilical artery (UA) pulsatility index (PI), middle cerebral artery (MCA) PI, cerebroplacental ratio (CPR), and their discordance recorded at the last ultrasound assessment before delivery or demise of one or both fetuses were converted into centiles or multiples of the median (MoM). The discordance was calculated as the larger value-smaller value/larger value. A logistic regression analysis was performed to identify, and adjust for, potential confounders. The predictive accuracy was assessed using receiver-operating characteristic curve analysis. The analysis included 620 (464 dichorionic diamniotic and 156 monochorionic diamniotic) twin pregnancies (1240 fetuses). Perinatal loss of one or both fetuses complicated 16 pregnancies (2.6%). The combination of EFW discordance and CPR discordance had the best predictive performance (area under the curve, 0.96; 95% confidence interval, 0.92-1.00) for perinatal mortality. The detection rate, false-positive rate, positive likelihood ratio, and negative likelihood ratio were 87.5%, 6.7%, 13.08, and 0.13, respectively. The EFW centile, EFW below the 10th centile (small for gestational age), UA PI discordance, MCA PI discordance, and MCA PI MoM were significantly associated with the risk of perinatal loss on univariate analysis, but these associations became nonsignificant after adjusting for other confounders (P = .097, P = .090, P = .687, P = .360, and P = .074, respectively). The UA PI MoM, CPR MoM, EFW discordance, and CPR discordance were all independent predictors of the risk of perinatal loss, even after adjusting for potential confounders (P = .022, P = .002, P < .001, and P = .010, respectively). EFW discordance and CPR discordance are independent predictors of the risk of perinatal loss in twin pregnancies. Their combination could identify the majority of twin pregnancies at risk of perinatal loss. These findings highlight the importance of discordance in Doppler indices of fetal hypoxia, as well as fetal size, in assessing the risk of perinatal mortality.

Dynamic hypoxic zones in Lake Erie compress fish habitat, altering vulnerability to fishing gears

Seasonal degradation of aquatic habitats from hypoxia occurs in numerous freshwater and coastal marine systems and can result in direct mortality or displacement of fish. Yet, fishery landings from these systems are frequently unresponsive to changes in the severity and extent of hypoxia, and population-scale effects have been difficult to measure except in extreme hypoxic conditions with hypoxia-sensitive species. We investigated fine-scale temporal and spatial variability in dissolved oxygen in Lake Erie as it related to fish distribution and catch efficiencies of both active (bottom trawls) and passive (trap nets) fishing gears. Temperature and dissolved oxygen loggers placed near the edge of the hypolimnion exhibited much higher than expected variability. Hypoxic episodes of variable durations were frequently punctuated by periods of normoxia, consistent with high-frequency internal waves. High-resolution interpolations of water quality and hydroacoustic surveys suggest that fish habitat is compressed during hypoxic episodes, resulting in higher fish densities near the edges of hypoxia. At fixed locations with passive commercial fishing gear, catches with the highest values occurred when bottom waters were hypoxic for intermediate proportions of time. Proximity to hypoxia explained significant variation in bottom trawl catches, with higher catch rates near the edge of hypoxia. These results emphasize how hypoxia may elevate catch rates in various types of fishing gears, leading to a lack of association between indices of hypoxia and fishery landings. Increased catch rates of fish at the edges of hypoxia have important implications for stock assessment models that assume catchability is spatially homogeneous.