Duration Of Hypoxia Research Articles

Abstract 2337: Recapitulating and targeting hypoxia-induced tumor metabolism using zebrafish tumor-derived xenografts-models

Abstract Hypoxia-induced metabolic pathways are excellent anti-tumor targets as these are specifically but broadly activated even under normoxia in cancer. However, these pathological metabolic profiles are often poorly recapitulated in vitro, and developing new drugs that target these tumor-specific metabolic enzymes therefore require in vivo models, even from an early stage. Screening of drug candidates or cell/PDX model libraries using zebrafish tumor xenograft (ZTX) models has become an attractive alternative to mice for fast assessment of drug efficacy in a variety of indications in vivo, but traditionally such models have not allowed for testing drugs that target hypoxia-induced metabolic pathways. Controlling the extent and duration of intratumor hypoxia in vivo has been done by mixing nitrogen gas directly into the water surrounding the larvae, and these systems have therefore not been amenable for high-throughput screening purposes. In order to advance the use of ZTX technologies and allow screening of drugs targeting hypoxia-induced metabolic pathways, a new, high-throughput platform for controlling hypoxia in zebrafish larvae is needed. Here we demonstrate the development of a ZTX platform in which hypoxia-induced pathophysiological changes in the tumor microenvironment are evaluated, and up-regulation of relevant drug targets are coupled to cell- and drug-screening capabilities. The system that we have developed here allows for screening of hundreds of tumor-bearing larvae in many different experimental groups at the same time, using normoxia and hypoxia in parallel. Using this innovative platform, we show that hypoxia exposure induces metastatic dissemination in a panel of 12 tumor cell lines, spanning multiple indications and that a specific drug, currently under clinical development, targeting hypoxia-induced tumor metabolism, is effective in killing tumor cells and reducing metastatic dissemination only under hypoxic conditions, thereby validating the proposed mechanism of action. In conclusion, we have developed a hypoxia-ZTX screening system that allows identification of alternate indications for approved drugs or drugs in phase II or III, expanding the possibility for on-labeled use of anti-cancer therapeutics. Specifically, we demonstrated that a novel drug candidate targeting a specific hypoxia-induced signaling pathway show high anti-tumor efficacy, reduces primary tumor burden, and inhibits metastatic dissemination. This drug would thereby be promising for expanded clinical development and on-label use. Citation Format: Gabriela Vazquez Rodriguez, Zaheer Ali, Malin Vildevall, Anna Erkstam, Andreas Goutopoulos, Anna Fahlgren, Lasse D. Jensen. Recapitulating and targeting hypoxia-induced tumor metabolism using zebrafish tumor-derived xenografts-models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2337.

Using zinc sulfate to improve pneumonia symptoms in children under 5 years of age: A case control study

Background: According to World Health Organization (WHO), Pneumonia is a form of acute respiratory infection that affects the lungs. Pneumonia is considered as the most important infection-induced cause of child mortality. Aim: To investigate the effect of prescribing zinc sulfate on improving the clinical symptoms of pneumonia in 2-59 months old children. Materials and Methods: This case control study was performed on 120 children with age of 2-59 months and complaining of fever, coughs, and tachypnea. The patients were randomly assigned into control (n=60), and intervention (n=60) using double blinding method. In the control group placebo was prescribed, while the intervention group received oral zinc sulfate 10 mg (1 ml/ kg in children younger than 12 months, and 20 mg/kg every 12 hours for children of 13-59 months. During hospitalization, every 12 hours the clinical symptoms of both groups including tachypnea, duration of fever, coughs, intercostal retraction, hypoxia, crackles-wheezing, and duration of hospitalization were recorded. At the beginning and end of the treatment, two blood samples were taken for determining the serum level of zinc. Results: The findings indicated that the serum level of zinc sulfate after the intervention increased significantly in the intervention group. There was a significant difference in the duration of fever and tachypnea between the intervention and control groups 36 hours post-hospitalization. Conclusion: Supplemental administration of zinc can expedite the healing process and results in faster resolution of clinical symptoms in children with pneumonia.

Mild Hypoxia Enhances the Expression of HIF and VEGF and Triggers the Response to Injury in Rat Kidneys.

BackgroundHypoxia contributes to a cascade of inflammatory response mechanisms in kidneys that result in the development of renal interstitial fibrosis and subsequent chronic renal failure. Nonetheless, the kidney possesses a self-protection mechanism under a certain degree of hypoxia and this mechanism its adaptation to hypoxia. As the hypoxia-inducible factor (HIF)–vascular endothelial growth factor (VEGF) axis is a key pathway for neovascularization, the activation of this axis is a target for renal hypoxia therapies.MethodsSprague–Dawley rats were exposed to normobaric hypoxia and subdivided into three groups, namely group A (21% O2), group B (10% O2), and group C (7% O2). Renal tissue samples were processed and analyzed to determine pathological morphological changes, the expression of HIF, VEGF, inflammation factor and vascular density.ResultsWe found that as the duration of hypoxia increased, destructive changes in the kidney tissues became more severe in group C (7% O2). In contrast, the increased duration of hypoxia did not exacerbate kidney damage in group B (10% O2). As the hypoxia was prolonged and the degree of hypoxia increased, the expression of HIF-1α increased gradually. As hypoxia time increased, the expression of VEGF increased gradually, but VEGF expression in group B (10% O2) was the highest. Group C (7% O2) had higher levels of IL-6, IL-10, and TNF-alpha. Additionally, the highest vascular density was observed in group B.ConclusionThese findings suggest that activating the HIF–VEGF signaling pathway to regulate angiogenesis after infliction of hypoxic kidney injury may provide clues for the development of novel CKD treatments.

A multielectrode array-based hypoxia model for the analysis of electrical activity in murine retinae.

Several eye diseases, for example, retinal artery occlusion, diabetic retinopathy, and glaucoma, are associated with retinal hypoxia. The lack of oxygen in the retina, especially in retinal ganglion cells (RGCs), causes cell damage up to cell degeneration and leads to blindness. Using multielectrode array recordings, an ex vivo hypoxia acute model was established to analyze the electrical activity of murine wild-type retinae under hypoxic stress conditions. Hypoxia was induced by exchanging the perfusion with oxygen-saturated medium by nitrogen-saturated medium. Hypoxic periods of 0min (control) up to 60min were tested on the retinae of adult female C57BL/6J mice. The electrical RGC activity vanished during hypoxia, but conditionally returned after the reestablishment of conventional test conditions. With increasing duration of hypoxia, the returning RGC activity decreased. After a hypoxic period of 30min and a subsequent recovery time of 30min, 59.43±11.35% of the initially active channels showed a restored RGC activity. The survival rate of retinal cells after hypoxic stress was analyzed by a live/dead staining assay using two-photon laser scanning microscopy. For detailed information about molecular changes caused by hypoxia, a microarray gene expression analysis was performed. Furthermore, the effect of 2-aminoethanesulfonic acid (taurine, 1mM) on retinae under hypoxic stress was tested. Treatment with taurine resulted in an increase in the RGC response rate after hypoxia and also increased the survival rate of retinal cells under hypoxic stress, confirming its potential as promising candidate for neuroprotective therapies of eye diseases.

Chronic hypoxia in pregnant mice impairs the placental and fetal vascular response to acute hypercapnia in BOLD-MRI hemodynamic response imaging

IntroductionBrief hypercapnic challenge causes acute placental hypoperfusion with fetal brain sparing on BOLD-MRI. We hypothesize that this non-invasive imaging strategy can distinguish between normal pregnancy and chronic placental hypoperfusion (using the maternal hypoxia model). MethodsEighteen pregnant female ICR mice were randomized to three groups: normoxia, late-onset hypoxia (12%O2;E13.5–17.5) and early-onset hypoxia (12%O2;E10.5–17.5). On E17.5, animals were imaged in a 4.7-T Bruker-Biospec MRI scanner. Fast coronal True-FISP was performed to identify organs of interest (placenta and fetal heart, liver and brain). BOLD-MRI was performed at baseline and during a 4-min hypercapnic challenge (5%CO2). %-change in placental and fetal signal was analyzed from T2*-weighted gradient echo MR images. Following MRI, fetuses and placentas were harvested, weighed and immuno-stained. ResultsIn normoxic mice, hypercapnia caused reduction in BOLD-MRI signal in placenta (−44% ± 7%; p < 0.0001), fetal liver (−32% ± 7%; p < 0.0001) and fetal heart (−54% ± 12%; p < 0.002), with relative fetal brain sparing (−12% ± 5%; p < 0.0001). These changes were markedly attenuated in both hypoxia groups. Baseline fetal brain/placenta SI ratio was highest in normoxic mice (1.14 ± 0.017) and reduced with increasing duration of hypoxia (late-onset hypoxia: 1.00 ± 0.026; early-onset hypoxia: 0.91 ± 0.016; p = 0.02). Both hypoxic groups exhibited fetal growth restriction with prominent placental glycogen-containing cells, particularly in early-onset hypoxia. There was increased fetal neuro- and intestinal-apoptosis in early-onset hypoxia only. ConclusionsBOLD-MRI with brief hypercapnic challenge distinguished between normoxia and both hypoxia groups, while fetal neuroapoptosis was only observed after early-onset hypoxia. This suggests that BOLD-MRI with hypercapnic challenge can identify chronic fetal asphyxia before the onset of irreversible brain injury.

Prediction of Hypoxia in Eutrophic Polymictic Lakes

AbstractQuantifying and predicting the drawdown of dissolved oxygen (DO) in lakes is important to ensuring healthy ecosystems and safe water sources. The characterization of DO depletion using available definitions and models requires extensive monitoring to obtain reliable results. These approaches have been mostly developed for seasonally stratified monomictic and dimictic lakes, limiting their applicability for polymictic systems which stratify and mix repeatedly. We compared the predicted duration of hypoxic events in the three basins of a large eutrophic polymictic lake (Clear Lake, CA, USA) by using three different one‐dimensional (1‐D) analytical approaches; two being original and requiring minimal input variables. Data on meteorology, lake temperature, and DO were all measured at multiple locations for one year and used to develop a novel method, named the Birge‐Winkler method. The daily net surface heat fluxes provided an energy term from which estimates of the onset and length of hypoxic periods could be made with minimal calibration. We used the Lake Number method to evaluate the level of accuracy of the Birge‐Winkler method. Finally, we estimated DO values next to the sediments using a Buoyancy Frequency method. Our results from the two original methods provided simple and effective tools for early warning of onset and duration of hypoxia, with a maximum of ±3–5 days uncertainty in the predictions. These indices can become powerful decision support tools for addressing aquatic ecological challenges triggered by hypoxia, including fish kills, internal nutrient loading, heavy metals release, and harmful algal blooms.

Sex Differences in Vascular Reactivity with Acute and Chronic Hypoxia

Objective Males and females may respond differently to hypoxic exposure at high altitude. Females have reduced vascular resistance in response to hypoxia, possibly due to differences in adrenergic control. We investigated the role of sex in vascular control during hypoxia. We hypothesized females have reduced vasoreactivity to sympathetic stressors compared to males during acute and prolonged hypoxia exposure. Methods We studied a convenient sample of 7 males and 6 females at three time points: 1) low altitude (Calgary AB, 1100m) breathing room air (normoxia; LOW) and acute isocapnic hypoxia (PETO2~50mmHg; PETCO2~32mmHg; ACUTE); 2) during early (day 2-3; EARLY) and 3) late (day 8-10; LATE) acclimatization at high altitude (White Mountain, CA; 3800m) breathing room air (PETO2~50mmHg) and hyperoxia (100% O2). Heart rate (HR), mean arterial pressure (MAP), and blood oxygen saturation (SpO2) were collected beat-by-beat. Participants performed a cold pressor test (CPT) to assess integrated cardiovascular reactivity to a sympathetic stressor. To isolate α1-adrenergic receptor sensitivity, we delivered a graded series of phenylephrine hydrochloride (PE) injections. Statistical analysis included a mixed model ANOVA, and Holm-Sidak post hoc tests when we identified main effects (α<0.05). Results In response to CPT, peak change in MAP decreased with hypoxia duration (p<0.001). There was also a significant interaction between condition and sex (p=0.038). While LOW (+17.0±5.9mmHg) and ACUTE (+15.3±4.7mmHg) responses were not different (p=0.565), males showed a marked decrease in peak MAP response to CPT at EARLY (+10.2±4.9mmHg) and LATE (+9.8±5.4mmHg) compared to LOW (both p<0.001). Similarly, LOW (+11.8±8.4mmHg) and ACUTE (+8.2±3.8mmHg) peak MAP responses to CPT were not different in females (p=0.137). Though female responses decreased between LOW and EARLY (+6.3±3.3mmHg; p=0.042), they returned to similar values by LATE (+9.7±7.5mmHg; p=0.479). Adrenergic sensitivity slope was decreased at altitude (p=0.025) independent of sex (p=0.977). LOW (0.33±0.21) and ACUTE (0.22±0.10) sensitivity were not different (p=0.309). Notably, sensitivity was reduced at altitude at LATE (0.14±0.16; p=0.043), but not significantly at EARLY (0.16±0.18; p=0.051) compared to LOW. Hyperoxia did not correct CPT responses or PE adrenergic sensitivity to low altitude values at EARLY (p<0.001; p=0.01, respectively) nor LATE (p=0.013; p=0.042, respectively). Conclusions Our data indicate decreased α1-adrenergic responsiveness with acclimatization underlies blunted vascular reactivity in both sexes. However, female responses to CPT returned to low altitude values following 8 days at altitude, indicating differential adaptation. Additional mechanisms influencing the vascular response to stress (e.g. less neuropeptide mediated constriction, higher β-adrenergic dilation) may account for lower responsiveness in females compared to males. Our results have implications for understanding vascular function at high altitude and in clinical conditions characterized by hypoxemia.

Dissolved Oxygen-And Temperature-Dependent Simulation of the Population Dynamics of Moon Jellyfish (Aurelia coerulea) Polyps

As the extent of hypoxia in coastal waters increases, the survivorship of jellyfish polyps relative to that of competing sessile organisms often increases, enabling them to reproduce more prolifically, leading to a medusa bloom in the following year. Quantifying the population of polyps can be used to predict when these blooms will occur. We used a time-delayed logistic equation to quantify the response to variable dissolved oxygen (DO) concentrations and temperatures in a population of moon jellyfish (Aurelia coerulea) polyps on substrates that carried competing sessile organisms. The availability of substrate depends on the DO threshold for each competitor, and substrates only become available to the polyps during hypoxic periods. We used the median sublethal concentration (SLC50) thresholds of hypoxia for different groups of benthic organisms to calculate the DO-dependent survivorship of A. coerulea polyps competing on the substrate. Since the median lethal time (LT50) for cnidarians is close to 240 h, we chose a 10-day delay in the time-delayed logistic equation. The carrying capacity is determined every 10 days depending on DO concentrations and temperature. The polyps reproduce by budding at a temperature-dependent rate after settling on the substrate during the hypoxic period, and thus, the annual polyp reproduction rate is determined by multiplying the temperature-dependent budding rate by the DO-dependent survivorship. The duration of hypoxia is a key factor determining the polyp population, which can increase more as the duration of hypoxia increases. Modeling simulations were compared to observed data. In this model, the DO and temperature distribution data make it possible to quantify variations in the population of the A. coerulea polyps, which can be used to predict the abundance and appearance of medusa the following year.

Cerebral oxygen saturation and autoregulation during hypotension in extremely preterm infants.

The impact of the permissive hypotension approach in clinically well infants on regional cerebral oxygen saturation (rScO2) and autoregulatory capacity (CAR) remains unknown. Prospective cohort study of blinded rScO2 measurements within a randomized controlled trial of management of hypotension (HIP trial) in extremely preterm infants. rScO2, mean arterial blood pressure, duration of cerebral hypoxia, and transfer function (TF) gain inversely proportional to CAR, were compared between hypotensive infants randomized to receive dopamine or placebo and between hypotensive and non-hypotensive infants, and related to early intraventricular hemorrhage or death. In 89 potentially eligible HIP trial patients with rScO2 measurements, the duration of cerebral hypoxia was significantly higher in 36 hypotensive compared to 53 non-hypotensive infants. In 29/36 hypotensive infants (mean GA 25 weeks, 69% males) receiving the study drug, no significant difference in rScO2 was observed after dopamine (n = 13) compared to placebo (n = 16). Duration of cerebral hypoxia was associated with early intraventricular hemorrhage or death. Calculated TF gain (n = 49/89) was significantly higher reflecting decreased CAR in 16 hypotensive compared to 33 non-hypotensive infants. Dopamine had no effect on rScO2 compared to placebo in hypotensive infants. Hypotension and cerebral hypoxia are associated with early intraventricular hemorrhage or death. Treatment of hypotension with dopamine in extremely preterm infants increases mean arterial blood pressure, but does not improve cerebral oxygenation. Hypotensive extremely preterm infants have increased duration of cerebral hypoxia and reduced cerebral autoregulatory capacity compared to non-hypotensive infants. Duration of cerebral hypoxia and hypotension are associated with early intraventricular hemorrhage or death in extremely preterm infants. Since systematic treatment of hypotension may not be associated with better outcomes, the diagnosis of cerebral hypoxia in hypotensive extremely preterm infants might guide treatment.

Antibiotic prescribing patterns in patients hospitalized with COVID-19: lessons from the first wave.

BackgroundA high proportion of hospitalized patients with COVID-19 receive antibiotics despite evidence to show low levels of true bacterial coinfection.MethodsA retrospective cohort study examining antibiotic prescribing patterns of 300 patients sequentially diagnosed with COVID-19. Patients were grouped into 3 sub-cohorts: Group 1 received no antibiotics, Group 2 received antibiotics for microbiologically confirmed infections and Group 3 was empirically treated with antibiotics for pneumonia. The primary aim was to identify factors that influenced prescription and continuation of antibiotics in Group 3. Secondary aims were to examine differences in outcomes between groups.ResultsIn total, 292 patients were included (63 Group 1, 35 Group 2, 194 Group 3), median age was 60 years (IQR 44–76) and the majority were ethnically Irish (62%). The median duration of antibiotics was 7 days (IQR 5–10). In Group 3, factors associated with prescription IV antibiotics on admission were raised C-reactive protein (CRP) (P = 0.024), increased age (P = 0.023), higher quick SOFA (P = 0.016) score and fever >37.5 °C (P = 0.011). Factors associated with duration of antibiotic course were duration of hypoxia (P < 0.001) and maximum respiratory support requirement (P = 0.013). Twenty-one patients in Group 3 had one or more antibiotic escalation events, most (n = 139) had no escalation or de-escalation of therapy.ConclusionsDuration of hypoxia and need for respiratory support may have acted as surrogate measures of improvement where usual response measures (CRP, neutrophilia, culture clearance) were absent. Continuous review of antibiotic prescriptions should be at the forefront of clinical management of hospitalized patients with COVID-19.

Regulation of satellite cells by exercise in hypoxic conditions: a narrative review.

To investigate in vivo the adaptations of satellite cell induced by exercise performed in acute or chronic hypoxic conditions and their contribution to muscle remodeling and hypertrophy. Search terms related to exercise, hypoxia and satellite cells were entered on Embase, PubMed and Scopus. Studies were selected for their relevance in terms of regulation of satellite cells by in vivo exercise and muscle contraction in hypoxic conditions. Satellite cell activation and proliferation seem to be enabled after acute hypoxic exercise via regulations induced by myogenic regulatory factors. Several studies reported also a role of the inflammatory pathway nuclear factor-kappa B and angiogenic factors such as vascular endothelial growth factor, both known to upregulate myogenesis. By stimulating angiogenesis, repeated exercise performed in acute hypoxia might contribute to satellite cell activation. Contrary to such exercise conditions, chronic exposure to hypoxia downregulates myogenesis despite the maintenance of physical activity. This impaired myogenesis might be induced by excessive oxidative stress and proteolysis. In vivo studies suggest that, in comparison to exercise or hypoxia alone, exercise performed in a hypoxic environment, may improve or impair muscle remodeling induced by contractile activity depending upon the duration of hypoxia. Satellite cells seem to be major actors in these dichotomous adaptations. Further research on the role of angiogenesis, types of contraction and autophagy is needed for a better understanding of their respective role in hypoxic exercise-induced modulations of satellite cell activity in human.

Hypoxia-induced expression of neuronal nitric oxide synthase in astrocytes of human corpus callosum.

Nitric oxide (NO) is a gaseous neurotransmitter largely diffused in the brain; among other functions, it regulates the cerebral blood flow in response to hypoxia. NO can be synthetized by three different isoforms of the enzyme NO synthase: neuronal (nNOS), typical of neurons, endothelial and inducible. The aim of this study was to assess nNOS expression in human corpus callosum (CC) astrocytes, and its relationship with the hypoxia duration. Autoptic samples of CC from adult human subjects have been processed with immunohistochemistry and immunofluorescence using antibodies anti-nNOS and anti-glial fibrillary acidic protein (GFAP), the astrocyte marker. Results demonstrated for the first time the presence of nNOS-immunopositive astrocytes in the human CC. In particular, nNOS-positive astrocytes were absent in subjects deceased after a short hypoxia; their number and labeling intensity, however, increased with hypoxia prolongation. Neuronal NOS immunopositivity of CC astrocytes seems thus related to the hypoxia duration and the consequent brain damage.

The Interplay Between Tumor Suppressor p53 and Hypoxia Signaling Pathways in Cancer.

Hypoxia is a hallmark of solid tumors and plays a critical role in different steps of tumor progression, including proliferation, survival, angiogenesis, metastasis, metabolic reprogramming, and stemness of cancer cells. Activation of the hypoxia-inducible factor (HIF) signaling plays a critical role in regulating hypoxic responses in tumors. As a key tumor suppressor and transcription factor, p53 responds to a wide variety of stress signals, including hypoxia, and selectively transcribes its target genes to regulate various cellular responses to exert its function in tumor suppression. Studies have demonstrated a close but complex interplay between hypoxia and p53 signaling pathways. The p53 levels and activities can be regulated by the hypoxia and HIF signaling differently depending on the cell/tissue type and the severity and duration of hypoxia. On the other hand, p53 regulates the hypoxia and HIF signaling at multiple levels. Many tumor-associated mutant p53 proteins display gain-of-function (GOF) oncogenic activities to promote cancer progression. Emerging evidence has also shown that GOF mutant p53 can promote cancer progression through its interplay with the hypoxia and HIF signaling pathway. In this review, we summarize our current understanding of the interplay between the hypoxia and p53 signaling pathways, its impact upon cancer progression, and its potential application in cancer therapy.

Association between early cerebral oxygenation and neurodevelopmental impairment or death in premature infants.

ObjectiveTo assess the relationship between cerebral oxygenation in the first 72 h of life and neurodevelopmental impairment (NDI) at 2 years corrected age in former premature infants.Study designProspective observational cohort study of 127 infants <32 weeks GA at birth with cerebral oxygenation monitoring using NIRS in the first 72 h of life.ResultsUsing a threshold cutoff for cerebral hypoxia, infants with NDI or death had increased duration of hypoxia (4 vs 2.3%, p = 0.001), which was more pronounced in the 23–27 week subgroup (7.6 vs 3.2%, p < 0.001). Individual generalized estimating equations to adjust for repeated measures were modeled in this subgroup for the physiologic parameters including StO2. StO2 < 67% was a predictor for death or NDI (OR 2.75, 95% CI 1.006, 7.5132, p = 0.049).ConclusionAn increased duration of cerebral hypoxia is associated with NDI or death in infants born <32 weeks GA.

CD15 immunostaining improves placental diagnosis of fetal hypoxia

IntroductionFetal hypoxic events with unclear predictive value are a common indication for placenta examination. We evaluated whether the use of CD15 immunostaining can improve the assessment of severity and duration of fetal hypoxia. MethodsWe compared placentas (37–42 gestational weeks) from stillborns/newborns with birth asphyxia (BA) and non-hypoxic newborns. Placental findings were studied in following groups: (1) acute BA (n = 11) due to placental abruption, (2) non-acute BA (n = 121) due to non-acute conditions, (3) non-BA (n = 46) in pregnancies with preeclampsia and gestational diabetes, and (4) controls (n = 30). ResultsA high expression of CD15 in feto-placental resistance vessels (FRVs) was present in non-acute BA (95.9%), but absent in acute BA, non-BA and controls (p < 0.0001). Furthermore, we found no causal relationship of high expression of CD15 in FRVs to coexisting placental conditions, including severity and mechanisms/patterns of placental injury, fetal erythroblastosis, and maternal conditions. According to a multivariate analysis, only a high expression of CD15 in FRVs was independently associated with severe non-acute fetal hypoxia ([OR] = 15.52; 95% [CI] = 5.92–40.67). DiscussionWe have defined a characteristic pattern of CD15 expression in FRVs that allows to interpret various clinical/placental conditions with respect to fetal hypoxia, with an improved predictability compared to conventional analyses. This approach represents a novel diagnostic strategy for placenta examination, which could indirectly assess severity and duration of intrauterine hypoxia in a heterogeneous population of newborns.

Apnoeic oxygenation for emergency anaesthesia of pre-hospital trauma patients

BackgroundEfficient and timely airway management is universally recognised as a priority for major trauma patients, a proportion of whom require emergency intubation in the pre-hospital setting. Adverse events occur more commonly in emergency airway management, and hypoxia is relatively frequent. The aim of this study was to establish whether passive apnoeic oxygenation was effective in reducing the incidence of desaturation during pre-hospital emergency anaesthesia.MethodsA prospective before-after study was performed to compare patients receiving standard care and those receiving additional oxygen via nasal prongs. The primary endpoint was median oxygen saturation in the peri-rapid sequence induction period, (2 minutes pre-intubation to 2 minutes post-intubation) for all patients. Secondary endpoints included the incidence of hypoxia in predetermined subgroups.ResultsOf 725 patients included; 188 patients received standard treatment and 537 received the intervention. The overall incidence of hypoxia (first recorded SpO2 < 90%) was 16.7%; 10.9% had SpO2 < 85%. 98/725 patients (13.5%) were hypoxic post-intubation (final SpO2 < 90% 10 minutes post-intubation).Median SpO2 was 100% vs. 99% for the standard vs. intervention group. There was a statistically significant benefit from apnoeic oxygenation in reducing the frequency of peri-intubation hypoxia (SpO2 < =90%) for patients with initial SpO2 > 95%, p = 0.0001. The other significant benefit was observed in the recovery phase for patients with severe hypoxia prior to intubation.ConclusionApnoeic oxygenation did not influence peri-intubation oxygen saturations, but it did reduce the frequency and duration of hypoxia in the post-intubation period. Given that apnoeic oxygenation is a simple low-cost intervention with a low complication rate, and that hypoxia can be detrimental to outcome, application of nasal cannulas during the drug-induced phase of emergency intubation may benefit a subset of patients undergoing emergency anaesthesia.

Investigating the Effect of Prescribing Zinc Sulfate on Improving the Clinical Symptoms of Pneumonia in 2-59-Month-Old Children

Background: Acute respiratory infections and especially pneumonia are considered as the most important infection-induced cause of child mortality in developing countries. We aimed to investigate the effect of prescribing zinc sulfate on improving the clinical symptoms of pneumonia in 2-59-month-old children. Materials and Methods: This clinical trial study was performed on 108 children complaining of fever, coughs, and tachypnea referring to three educational hospitals of Mashhad (Ghaem, Imam Reza, and Dr. Sheikh). The patients were randomly assigned into control (n=54), and intervention (n=54). In the control group placebo was prescribed, while the intervention group received oral zinc sulfate 10 mg (1 ml/ kg in children younger than one year, and 20 mg/kg for children above one year every 12 hours. During hospitalization, every 12 hours the clinical symptoms of both groups including tachypnea, duration of fever, coughs, intercostal retraction, hypoxia, crackles-wheezing, and duration of hospitalization were recorded. At the beginning and end of the treatment, two blood samples were taken for determining the serum level of zinc. Results: The findings indicated that the serum level of zinc sulfate after the intervention increased significantly in the intervention group (p <0.001). There was a significant difference in the duration of fever between the intervention and control groups 24 hours after hospitalization (p=0.014) and 36 hours post-hospitalization (p=0.02). Comparing the presence or absence of tachypnea in the intervention and control groups, there was a significant difference at 36 hours post-hospitalization (p=0.02). Conclusion: Based on the results, zinc supplement was effective for patients with pneumonia in reducing the duration of fever and number of breaths, but it had no significant effect on the duration of coughs and hospitalization.

Pulmonary artery hemodynamics are associated with duration of nocturnal desaturation but not apnea-hypopnea index.

Sleep-disordered breathing and nocturnal hypoxia are prevalent among patients with precapillary pulmonary hypertension (PAH). The rationale for these associations remains unclear and these relationships have not been well studied in other forms of pulmonary hypertension (PH). We hypothesized that severity of sleep-disordered breathing and nocturnal hypoxia are associated with worsening pulmonary hemodynamics, regardless of hemodynamic profile. Four hundred ninety-three patients were divided into 4 groups: 1) no PH, 2) postcapillary pulmonary hypertension, 3) PAH, and 4) mixed PAH/postcapillary pulmonary hypertension. The relationship between right heart catheterization measurements and apnea-hypopnea index or the percentage of sleep time spent with oxygen saturation < 90% (T90) was calculated using multiple linear regression. Analysis of variance was used for between-group comparisons. Statistical models were adjusted for known confounders. Apnea-hypopnea index did not differ between hemodynamic subgroups (P = .27) and was not associated with right atrial pressure (.11 ± .19, P = .55), cardiac index (.25 ± 1.64, P = .88), mean pulmonary artery pressure (-.004 ± .09, P = .97), or pulmonary artery occlusion pressure (.16 ± .14, P = .26). While patients with PH had a higher T90 than those without (mean 24.2% vs 11.7%, P < .001), there was no difference in T90 between individual PH subgroups (P = .70). T90 was associated with mean pulmonary artery pressure (.55 ± .10, P < .0001), PVR (1.61 ± .49, P = .001), and right atrial pressure (.50 ± .20, P = .01), but not cardiac index (-.76 ± 1.73, P = .66), or pulmonary artery occlusion pressure (.23 ± .15, P = .13). Increased PH severity was associated with longer duration of nocturnal hypoxia regardless of hemodynamic subgroup.

NEUROSONOGRAPHY SPECTRUM OF HYPOXIC ISCHEMIC ENCEPHALOPATHY

Introduction: Neonatal hypoxic-ischemic encephalopathy (HIE) is a very catastrophic condition that may result in severe neurologic deficits or even death. Neuroimaging with transcranial ultrasound (US) is a valuable tool in the workup of patients with HIE. The pattern of brain injury depends on the severity and duration of hypoxia and degree of brain maturation.1&#x0D; Aim: To study imaging spectrum of various stages of HIE&#x0D; Objective: To determine severity of HIE on basis of Neuro-sonography.&#x0D; Settings and Design: The study was conducted at J K Lone Paediatric hospital attached to SMS hospital. It is a Prospective study.&#x0D; Materials and Method: Pre term neonates having some history of hypoxia antenatally or perinatally like placental abruption, low Apgar at delivery, seizures coming to JK lone Paediatric Hospital attached to SMS hospital referred to Dept of Radiodiagnosis for evaluation of HIE were scanned using Transcranial ultrasound it included grayscale on Hitachi machine.&#x0D; Results- Different grades of HIE changes were witnessed. Out of 33 cases:&#x0D; 5 neonates were sonographically normal, 3 showed grade 1 GMH, 3 showed grade 2 GMH, 4 showed grade 3 GMH and 4 showed grade 4 . 3 neonates showed grade 1 PVL, 2 grade 2 PVL, 4 showed grade 3 PVL, 5 showed grade 4 PVL. In doppler findings of ACA, it was noted the RI (resistive index) was on the higher side.&#x0D; Conclusion: Neurosonography and doppler is very helpful non-invasive tool to detect early changes of HIE and assess severity and progression of hypoxic brain injury. &#x0D; Keywords: HIE, hypoxic brain injury, germinal matrix haemorrhage and periventricular leucomalacia

Peri-ictal hypoxia is related to extent of regional brain volume loss accompanying generalized tonic-clonic seizures.

ObjectivesHypoxia, or abnormally low blood‐oxygen levels, often accompanies seizures and may elicit brain structural changes in people with epilepsy which contribute to central processes underlying sudden unexpected death in epilepsy (SUDEP). The extent to which hypoxia may be related to brain structural alterations in this patient group remains unexplored.MethodsWe analyzed high‐resolution T1‐weighted magnetic resonance imaging (MRI) to determine brain morphometric and volumetric alterations in people with generalized tonic‐clonic seizures (GTCS) recorded during long‐term video‐electroencephalography (VEEG), recruited from two sites (n = 22), together with data from age‐ and sex‐matched healthy controls (n = 43). Subjects were sub‐divided into those with mild/moderate (GTCS‐hypox‐mild/moderate, n = 12) and severe (GTCS‐hypox‐severe, n = 10) hypoxia, measured by peripheral oxygen saturation (SpO2) during VEEG. Whole‐brain voxel‐based morphometry (VBM) and regional volumetry were used to assess group comparisons and correlations between brain structural measurements as well as the duration and extent of hypoxia during GTCS.ResultsMorphometric and volumetric alterations appeared in association with peri‐GTCS hypoxia, including volume loss in the periaqueductal gray (PAG), thalamus, hypothalamus, vermis, cerebellum, parabrachial pons, and medulla. Thalamic and PAG volume was significantly reduced in GTCS patients with severe hypoxia compared with GTCS patients with mild/moderate hypoxia. Brainstem volume loss appeared in both hypoxia groups, although it was more extensive in those with severe hypoxia. Significant negative partial correlations emerged between thalamic and hippocampal volume and extent of hypoxia, whereas vermis and accumbens volumes declined with increasing hypoxia duration.SignificanceBrain structural alterations in patients with GTCS are related to the extent of hypoxia in brain sites that serve vital functions. Although the changes are associative only, they provide evidence of injury to regulatory brain sites related to respiratory manifestations of seizures.