Chronic Hypoxemia Research Articles

SAT-311 Retroperitoneal Paraganglioma in a Patient Post-Fontan: The Association

Background: Pheochromocytomas and paragangliomas (PHEO/PGL) are catecholamine producing tumors of the autonomous nervous system that arise from the chromaffin cells in the adrenal medulla or extra-adrenal paraganglionic tissue. About 40% of these tumors are associated with germline mutations of the VHL, RET, NF1, SDHA, SDHB, SDHC, SDHD etc.(1). However, there are reports of chronic hypoxemia triggering the development of such tumors, especially in patients with congenital cyanotic heart disease (CCHD). PHEO/PGL in association with a CCHD was first reported in 5 cases in 1964(2). The youngest reports of this co-occurrence has been in two 13 year old male patients post-Fontan procedure, that presented about 10 years after this intervention(3, 4). Studies on patients with CCHD that developed PHEO/PGL, showed that patients were diagnosed at a median age of 24-31years, with a mean oxygen saturation of ~87% at diagnosis and a cyanosis duration of 6 - 25 years (4, 5). Case: We report a 12 year old female with a history of hypoplastic left heart, post lateral tunnel non-fenestrated Fontan procedure with mitral and tricuspid valvuloplasty performed at 4 years of age. Her resting oxygen saturation at presentation was 86-92%. She presented with frequent episodes of sweating, anxiety, chest pain and sustained hypertension (~200/90 mm Hg) refractory to anti-hypertensives, for a few months. A 24-hr urine collection showed a normetanephrine level of 5125mcg (ref: 67 - 503 mcg/24hr) with a plasma normetanephrine level of 37.8nmol/L (ref: 0 - 0.89nmol/L). No germ-line mutations were identified in the genes commonly associated with PHEO/PGL (MAX, NF1, RET, SDHAF2, SDHA, SDHB, SDHC, SDHD, TMEM127, VHL). CT scan revealed a left upper quadrant abdominal mass which on surgical resection was noted to be a para-aortic mass. Cytology confirmed a paraganglioma tumor. Conclusion: PHEO/PGL are rare entities in the pediatric population; however, their incidence is significantly higher among patients with CCHD. Though, most patients present during adulthood with PHEO/PGL, some may present earlier, and those caring for CCHD patients must be mindful of this complication.

Predictive factors of cognitive impairment in Tunisian population with non valvular atrial fibrillation

Atrial fibrillation (AF) is the most frequently encountered arrhythmia and is largely associated with cognitive decline. Obstructive sleep apnea (OSA) may lead to cognitive decline through chronic sleep fragmentation and intermittent hypoxemia. Does the association between these pathologies increase cognitive impairment's likelihood? Determine the prevalence of cognitive deficit in AF patients and to identify the predictive factors of this disorder. The study concerned 81 patients with non valvular AF. Patients with a history of stroke were not included. The cognitive performance was assessed by evaluating different parameters: Memory, attention and executive functions (inhibition, shifting, updating/monitoring information). A cognitive deficit was considered if at least one of these parameters was defective. The average age was 66,2 ± 9.7 years old. A detailed questioning regarding cognitive function objectified that 78% of patients had cognitive deficit. An age greater than 68 years, was significantly related to cognitive disorders ( P = 0.002). Symptomatic AF with EHRA class III or IV, was statistically associated with cognitive impairment ( P = 0.014). Referring to polygraph's results, 74 patients (91.4%) had OSA. Moderate and severe OSA (AHI > 15) were significantly associated with cognitive impairment ( P = 0.004). Total desaturation time under 90% was correlated with cognitive decline ( P = 0.003) with a limit value for predicting cognitive deficit, of 4 minutes (sensitivity = 70%, Specificity = 68%). The multivariate study found that predictors of cognitive impairment in AF patients were: age > 68 years( P = 0.012, OR = 6.3), AHI > 15 ( P = 0.049, OR = 3.8) and an EHRA class III or IV ( P = 0.025, OR = 5). Our study revealed that moderate to severe OSA is an independent predictive factor of cognitive impairment in AF patients. Thus, treating OSA by continuous airway pressure may have a beneficial effect on cognitive function.

Biochemistry in Assessing the Inflammatory Response of the Respiratory System Due to Experimental Exposure to Glass Fibres

Given the structural resemblances between glass fiber and asbestos, it is important to understand the mechanisms through which exposure to glass fibers may affect the respiratory system. To study the effect of glass fiber on rat lung through intratracheal exposure, considering the subject�s weight variation, together with haematological parameters, C-reactive protein (CRP), total number of lymphocytes, and IL8 concentration in bronchoalveolar lavage. We performed an intratracheal instillation study on four groups of 8 randomly selected Wistar rats, by administering 3 different doses of glass fiber. The hematocrit value was an indirect indicator of chronic hypoxemia; leukocytes and the C-reactive protein assessed systemic inflammation, and total number of lymphocytes and IL8 concentration in bronchoalveolar lavage fluid determined the lung�s inflammatory response. Weight variation evaluated in all 8 measurements revealed no statistically significant changes (p=0.768). The decrease in mean blood leukocytes was interpreted in relation with the glass fiber dose, with a statistically significant difference between the study groups (p=0.003). Statistically significant differences were found in the CRP values, with dose correlations (p[0.001). The bronchoalveolar lavage fluid showed increased levels of IL-8 (p[0.05), and decrease of lymphocytes (p[0.001) in correlation with the administered glass fiber dose. The inflammatory response following exposure to glass fibers in rats is correlated with administrated glass fiber dose. The alterations described as a result of intratracheal glass fiber instillation could predict the effects which occupational exposure to glass fiber may produce in humans.

New guidelines for home oxygen therapy in children

New guidelines for home oxygen therapy in children

Spermine on Endothelial Extracellular Vesicles Mediates Smoking-Induced Pulmonary Hypertension Partially Through Calcium-Sensing Receptor.

Objective- This study aims to determine whether and how the enriched metabolites of endothelial extracellular vesicles (eEVs) are critical for cigarette smoke-induced direct injury of endothelial cells and the development of pulmonary hypertension, rarely explored in contrast to long-investigated mechanisms secondary to chronic hypoxemia. Approach and Results- Metabonomic screen of eEVs from cigarette-smoking human subjects reveals prominent elevation of spermine-a polyamine metabolite with potent agonist activity for the extracellular CaSR (calcium-sensing receptor). CaSR inhibition with the negative allosteric modulator Calhex231 or CaSR knockdown attenuates cigarette smoke-induced pulmonary hypertension in rats without emphysematous changes in lungs or chronic hypoxemia. Cigarette smoke exposure increases the generation of spermine-positive eEVs and their spermine content. Immunocytochemical staining and immunogold electron microscopy recognize the spermine enrichment not only within the cytosol but also on the outer surface of eEV membrane. The repression of spermine synthesis, the inhibitory analog of spermine, N1-dansyl-spermine, Calhex231, or CaSR knockdown profoundly suppresses eEV exposure-mobilized cytosolic calcium signaling, pulmonary artery constriction, and smooth muscle cell proliferation. Confocal imaging of immunohistochemical staining demonstrates the migration of spermine-positive eEVs from endothelium into smooth muscle cells in pulmonary arteries of cigarette smoke-exposed rats. The repression of spermine synthesis or CaSR knockout results in attenuated development of pulmonary hypertension induced by an intravascular administration of eEVs. Conclusions- Cigarette smoke enhances eEV generation with spermine enrichment at their outer surface and cytosol, which activates CaSR and subsequently causes smooth muscle cell constriction and proliferation, therefore, directly leading to the development of pulmonary hypertension.

Chronic Intermittent Hypoxemia in Patients with Obstuctive Sleep Apnea Syndrome Causes Reduction of Peripheral Nerve Motor Fibers (Unit Number)

Chronic Intermittent Hypoxemia in Patients with Obstuctive Sleep Apnea Syndrome Causes Reduction of Peripheral Nerve Motor Fibers (Unit Number)

REgistry-based randomized controlled trial of treatment and Duration and mortality in long-term OXygen therapy (REDOX) study protocol

ObjectiveLong-term oxygen therapy (LTOT) during 15 h/day or more prolongs survival in patients with chronic obstructive pulmonary disease (COPD) and severe hypoxemia. No randomized controlled trial has evaluated the net effects (benefits or harms) from LTOT 24 h/day compared with 15 h/day or the effect in conditions other than COPD. We describe a multicenter, national, phase IV, non-superiority, registry-based, randomized controlled trial (R-RCT) of LTOT prescribed 24 h/day compared with 15 h/day. The primary endpoint is all-cause-mortality at 1 year. Secondary endpoints include cause-specific mortality, hospitalizations, health-related quality of life, symptoms, and outcomes in interstitial lung disease.Methods/designPatients qualifying for LTOT are randomized to LTOT 24 h/day versus 15 h/day during 12 months using the Swedish Register for Respiratory Failure (Swedevox). Planned sample size in this pragmatic study is 2126 randomized patients. Clinical follow-up and concurrent treatments are according to routine clinical practice. Mortality, hospitalizations, and incident diseases are assessed using national Swedish registries with expected complete follow-up. Patient-reported outcomes are assessed using postal questionnaire at 3 and 12 months.DiscussionThe R-RCT approach combines the advantages of a prospective randomized trial and large clinical national registries for enrollment, allocation, and data collection, with the aim of improving the evidence-based use of LTOT.Trial registrationClinical Trial registered with www.clinicaltrials.gov, Title: REgistry-based Treatment Duration and Mortality in Long-term OXygen Therapy (REDOX); ID: NCT03441204.

Handgrip Strength and Pulmonary Disease in the Elderly: What is the Link?

Societies in developed countries are aging at an unprecedented rate. Considering that aging is the most significant risk factor for many chronic lung diseases (CLDs), understanding this process may facilitate the development of new interventionist approaches. Skeletal muscle dysfunction is a serious problem in older adults with CLDs, reducing their quality of life and survival. In this study, we reviewed the possible links between handgrip strength (HGS)—a simple, noninvasive, low-cost measure of muscle function—and CLDs in the elderly. Different mechanisms appear to be involved in this association, including systemic inflammation, chronic hypoxemia, physical inactivity, malnutrition, and corticosteroid use. Respiratory and peripheral myopathy, associated with muscle atrophy and a shift in muscle fiber type, also seem to be major etiological contributors to CLDs. Moreover, sarcopenic obesity, which occurs in older adults with CLDs, impairs common inflammatory pathways that can potentiate each other and further accelerate the functional decline of HGS. Our findings support the concept that the systemic effects of CLDs may be determined by HGS, and HGS is a relevant measurement that should be considered in the clinical assessment of the elderly with CLDs. These reasons make HGS a useful practical tool for indirectly evaluating functional status in the elderly. At present, early muscle reconditioning and optimal nutrition appear to be the most effective approaches to reduce the impact of CLDs and low muscle strength on the quality of life of these individuals. Nonetheless, larger in-depth studies are needed to evaluate the link between HGS and CLDs.

Diagnosis and management of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. Its signs and symptoms are relatively non-specific, and patients often present with chronic cough, progressive dyspnea, resting or exertional hypoxemia, and inspiratory crackles on lung auscultation. Definitive diagnosis requires the exclusion of known causes of pulmonary fibrosis and identification of the usual interstitial pneumonia (UIP) pattern of disease either on high-resolution computed tomography (HRCT) scan of the chest or on surgical lung biopsy. Multidisciplinary discussion involving pulmonologists, radiologists, and pathologists with expertise in the diagnosis of IPF and other forms of interstitial lung disease is recommended and often required. Management focuses on anti-fibrotic therapy and early referral to lung transplant centers for those who are candidates. This review will discuss the current recommendations for the diagnosis, prognostication, and management of patients with IPF.

Long-Term Oxygen Therapy.

Long-term oxygen therapy (LTOT) is an established treatment for patients with chronic hypoxemia. Its scientific basis is derived mainly from two trials from the early 1980s that showed a survival advantage for patients with chronic obstructive pulmonary disease (COPD) treated with LTOT. Robust data are not available for other diseases associated with hypoxemia. This review is based on pertinent publications retrieved by a selective search in PubMed. The use of LTOT for 15 to 16 hours per day (or, better, 24 hours per day) is recommended in current guidelines for patients with chronic hypoxemia (PaO2 ≤ 55 mm Hg) because this treatment was found to be associated with a lower mortality rate compared to no LTOT (33% vs. 55%, p <0.05) based on data from the early 1980s. In the short term, oxygen administration to a hypoxemic patient can improve oxygen saturation by nine percentage points and improve physical performance to a clinically relevant extent (6-minute walking test: + 37 m, p <0.001). The available data do not support the use of LTOT for normoxemic patients. LTOT should only be administered for strict indications, in accordance with the guidelines, and only in a form suitable for the individual patient. Skin burns can occur as a side effect of LTOT because of contact explosions with any type of fire. The acquisition of further robust data would be desirable, particularly with respect to patient-relevant outcome parameters including quality of life, performance status, and mortality. Moreover, the German guidelines on oxygen therapy need to be updated.

Fetal hypoxemia causes abnormal myocardial development in a preterm ex utero fetal ovine model.

In utero hypoxia is a major cause of neonatal morbidity and mortality and predisposes to adult cardiovascular disease. No therapies exist to correct fetal hypoxia. In a new ex utero fetal support system, we tested the hypothesis that hypoxemic support of the fetus impairs myocardial development, whereas normoxic support allows normal myocardial development. Preterm fetal lambs were connected via umbilical vessels to a low-resistance oxygenator and placed in a sterile-fluid environment. Control normoxic fetuses received normal fetal oxygenation, and hypoxemic fetuses received subphysiologic oxygenation. Fetuses with normal in utero development served as normal controls. Hypoxemic fetuses exhibited decreased maximum cardiac output in both ventricles, diastolic function, myocyte and myocyte nuclear size, and increased myocardial capillary density versus control normoxic fetuses. There were no differences between control normoxic fetuses in the fetal support system and normal in utero controls. Chronic fetal hypoxemia resulted in significant abnormalities in myocyte architecture and myocardial capillary density as well as systolic and diastolic cardiac function, whereas control fetuses showed no differences. This ex utero fetal support system has potential to become a significant research tool and novel therapy to correct fetal hypoxia.

Vascular changes in fetal growth restriction: clinical relevance and future therapeutics.

Fetal growth restriction (FGR) affects about 5-10% pregnancies and is associated with poorer outcomes in the perinatal period. Additionally, long standing epidemiological data support its association with chronic diseases such as hypertension and diabetes. Cardiac and vascular adaptations in response to chronic hypoxemia due to utero-placental insufficiency are hallmarks of fetal adaptations. Investigators have attempted to identify these changes in the placenta at the microscopic and molecular level. The ex vivo dual perfusion model of the placenta enables the study of placental haemodynamics in growth-restricted pregnancies. Persistent arterial abnormalities (thickness and stiffness) noted on vascular ultrasound during fetal life through to the young-adult age group for those affected by FGR, seem to be a plausible link between in utero events and chronic circulatory diseases. Using these, this review reflects current thought on vascular maladaptive changes in the FGR cohorts and the role in investigating current and future therapeutics.

Is It Better to Give or to Receive?

Is It Better to Give or to Receive?

Acquired Secondary Erythrocytosis in Long-Term Survivors of Allogeneic Hematopoietic Stem Cell Transplantation

Background: Erythrocytosis is a condition of increased red blood cell mass, as reflected by laboratory findings of elevated hemoglobin (HGB) and hematocrit (HCT). Erythrocytosis is classified into primary (polycythemia) and secondary, depending on its etiology. Secondary polycythemia most commonly develops in the setting of chronic hypoxemia which triggers increased production of erythropoietin by the kidneys. We have observed several patients in our hematology clinic who were long-term survivors after allogeneic hematopoietic stem cell transplant (allo-HSCT), and subsequently developederythrocytosisduring their follow up without obvious secondary causes. On literature review we found two single-institutional studies with estimated incidence of this unexpected complication reported as 0.45 and 1.1% respectively. Majority of described patients in the literature were young males with aplastic anemia (AA).Methods: To establish the incidence of post-transplant erythrocytosis in long termsurvivors of allo-HSCT, we conducted a retrospective single site chart review study using theWVUdatabase.All patients above age of 18 at the time of transplantation regardless the initial diagnosis that lead to transplantation and type of allo-HSCT were included. Patients with disease relapse and follow up less than 12 months were excluded. We also excluded patients with underlying conditions that are commonly associated with secondary erythrocytosis. Following definition of polycythemia or erythrocytosis was used: a) HCT >48% in women or >49% in men and/or HGB >16.0 g/dL in women or >16.5 g/dL in men (as extrapolated from WVO 2016 PV criteria); b) HGB/HCT elevation consistent on at least two measurements 3 months apart.Results: We identified 133 eligible patients for final analysis. Among them, 12 (9.0%) developed erythrocytosis in amedian time from initial allo-HSCT 44.5 months (11.8-60.1). Peripheral blood Jak2V617F mutation was tested in 8/12 patients - negativeinall. Serum erythropoietin (EPO) level was tested for 9/12 patients and found to be not suppressed in all cases to the level of HGB/HCT, median 11.1 mU/ml (4.9-18.6). All patients were non-smokers and 11/12 patients had different degree of GVHD requiring immunosuppressive therapy. The highest levels of HGB/HCT were observed in two patients with aplastic anemia and one of them required periodic therapeutic phlebotomies. In rest of the patients erythrocytosis was relatively mild but persistent. Details on our findings are presented in a table below.Conclusions: Acquired secondary erythrocytosis is not uncommon in long-term survivors of allo-HSCT, estimated at 9.0% in our patient cohort. The exact mechanisms of erythrocytosis in this setting are unknown but probably related to dysregulated EPO production and response. [Display omitted] DisclosuresCraig:Celgene: Research Funding; Novartis: Research Funding; Actinium Pharmaceuticals: Research Funding.

Metabolic Profile & Body Composition in Egyptian Children with Transfusion-Dependent Egyptian B-Thalassemia

Background: Metabolic challenges in beta thalassemia major (BTM) carry an additional burden to both chronic anemia and iron overload. Although optimal nutritional support for children with BTM is mandatory, health insurance cover only blood transfusion and chelation therapy. Nutrition support remains subtle for both the family and governmental interest especially in developing countries. Aim: To assess growth, total body composition, lipid and glucose hemostasis in Egyptian children with BTM in relation to iron overload and state of chronic hypoxemia. Subjects and methods: 200 Egyptian children with BTM were recruited, they were 99 females (49.5%) and 101 male (50.5%) and their mean age was 12.15 ± 4.23 years. 50 age- and sex-matched healthy children with same socio-economic background were also enrolled. All of them subjected to history taking; thorough clinical examination, anthropometric measurements (weight, height, mid arm circumference, skin fold thickness and body mass index), body composition analysis (using bioelectric impedance analysis device) and dietetic assessment (using 24-hours dietetic recall). Serum lipid profile (high-density lipoprotein (HDL), low-density lipoprotein (LDL), cholesterol and triglyceride), C-peptide and serum insulin were assessed. Results: Most children with BTM had families with high birth order and nearly half of them had positive family history, in addition consanguinity was reported to be 1.5 times in BTM compared to what was reported in controls. Almost half of the patients were from Cairo, the other half were from the economically less privileged Upper Egypt. Most of patients were diagnosed presented in 1st two years of life at mean age of 1.52 ± 1.66 and 1st transfusion was initiated within first four months after initial diagnosis. Most of patient transfused on low mean pre-transfusion hemoglobin of 8.4± 2.6 g/dl. Most studied BTM had iron overload, median (IQR) of serum ferritin was 1800 (1149 - 3100) ng/ml in the last 2 years, with median (IQR) duration on regular iron chelation was 4 (2-6) years and 12.5% of patients were non-compliant. Children with BTM had a significantly lower nutritional intake (kilocalories, protein, carbohydrate, calcium, and phosphorus) than controls with negative impact on anthropometric parameters and body composition parameters both in pubertal and pre-pubertal stage. There was significant increase in body fat value and percent in female BTM compared to male BTM. While there was significant increase in muscle mass % and body water % in males BTM. Children with BTM had significantly higher triglycerides levels however lower cholesterol, LDL, HDL, insulin and C-peptide compared to control. Factors including age, gender, caloric intake, mean pre-transfusion hemoglobin, transfusion burden, splenectomy, viral hepatitis comorbidity, mean serum ferritin, serum insulin, and HDL have impact on body composition in children with BTM.Conclusion: Poor caloric intake with low pre-transfusion hemoglobin and higher serum ferritin were the main risk factors for poor anthropometric parameters in all ages. Regular assessment of nutrition is crucial for the health of children with thalassemia.Keywords: Thalassemia, Body composition; Nutritional deficiency; Diabetes; Lipid DisclosuresNo relevant conflicts of interest to declare.

Phosphodiesterase type 5 inhibitors improve microvascular dysfunction markers in pulmonary arterial hypertension associated with congenital heart disease.

Ideally, vasodilator therapies for pulmonary arterial hypertension (PAH) should have a favorable impact on markers of vascular dysfunction, in addition to their known effects on hemodynamics, cardiac function, and patient's physical capacity. We analyzed circulating (plasma) markers of endothelial and platelet activation/dysfunction (enzyme-linked immunoassays) in the specific setting of advanced PAH associated with congenital heart disease, during the course of sildenafil and tadalafil therapies. Thirty-one patients were enrolled (age 10-54years), most of them with chronic hypoxemia and elevated hematocrit. Drugs were administered orally for 6months (sildenafil [n=16], 20mg t.i.d.; tadalafil [n=15], single daily dose of 40mg). Measurements were performed at baseline, and 90 and 180days. Compared to controls, patients had elevated baseline β-thromboglobulin (β-TG, P=.002), P-selectin (P=.027), tissue-type plasminogen activator (t-PA, P=.009), and von Willebrand factor antigen (VWF:Ag, P=.010). Thrombomodulin was importantly reduced (TM, P<.001), while soluble CD40 Ligand was not changed (P=.320). Tadalafil administration was associated with improvement of β-TG (P=.004), t-PA (P=.003) and TM (P=.046) levels, while P-selectin was improved by sildenafil treatment only (P=.034). VWF:Ag improved transiently in the sildenafil group (P=.019). Both therapies were associated with improvement of the physical capacity (functional class and distance walked during the 6-minute test, P<.05), hematocrit and hemoglobin level (P<.05), and health-related quality of life (physical and mental components, P<.05). In PAH associated with congenital heart disease, phosphodiesterase 5 inhibitors seem to have beneficial actions at microcirculatory level, beyond the proposed effects as vasodilators.

Seizures in Idiopathic Pulmonary Arterial Hypertension

AbstractPulmonary arterial hypertension (PAH) is a progressive pulmonary vasculopathy. A 29-year-old female patient presenting with dyspnea and syncope within 6 hours of onset was admitted to our hospital. The patient stated that she looked for a neurologist months ago because she experienced abrupt shaking limbs occurring during physical activity. She was diagnosed with focal seizure, and carbamazepine (CBZ) was started. On admission, she reported that the dyspnea had started in the last week and recurrent episodes of syncope in the last few hours. A right heart catheterization was diagnostic of PAH. She was started on spironolactone, furosemide, sildenafil, warfarin, and supplemental oxygen. On 10th admission day, the patient was seizure free and the dose of CBZ was tapered. In the follow-up, the patient remained seizure free. An investigation to search for a chronic lung disease or hypoxemia, systemic disorder, hematological disorder, and metabolic disorder was negative.

PARADOXICAL WORSENING HYPOXEMIA WITH MECHANICAL VENTILATION IN A PATIENT WITH BILATERAL PNEUMONIA

SESSION TITLE: Medical Student/Resident Pulmonary Physiology SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is associated with chronic hypoxemia due to right-to-left shunting. We present a patient with a history of COPD and adenocarcinoma with bilateral pneumonia who developed severe hypoxemia on mechanical ventilation. CASE PRESENTATION: A 64-year-old male with a history of COPD and Stage IIIA adenocarcinoma presented in respiratory distress. Chest x-ray (CXR) revealed bilateral opacities. Arterial blood gas (ABG) on a non-rebreather mask with a fraction of inspired oxygen (FiO2) 100% was pH of 7.42, pCO2 40.9, and PaO2 of 79.3. He was started on broad spectrum antibiotics. CT chest angiogram was negative for a pulmonary embolism, but showed a 2.8 cm spiculated mass in the right upper lobe, and extensive bilateral ground glass opacities. Echocardiography confirmed right-to-left intrapulmonary shunting with normal right ventricular function. With worsening hypoxemia, despite noninvasive-positive-pressure support, the patient was intubated with etomidate and rocuronium and placed on volume-control ventilation (VCV) with positive-end-expiratory pressure (PEEP) 5 cmH2O; respiratory rate 16, and FiO2 100%. His SpO2 dropped to 60% and was switched to pressure-control ventilation. He subsequently became hypotensive and bradycardic with a PEA arrest. A code blue was initiated with ROSC after several minutes. Repeat ABG showed: pH 7.154, pCO2 52, PaO2 63.7; and SaO2 76.4. Patient was changed back to VCV with PEEP 10 cmH2O; respiratory rate 24, and FiO2 100% that improved SpO2 to 80-82% temporarily. Despite trials of escalating PEEP and mode changes, the SpO2 declined to 50-60%. After an aborted recruitment maneuver, a second episode of PEA arrest occurred with ROSC, but he continued to have low SpO2 values, which was confirmed with ABG. Repeat CXR showed worsening bilateral infiltrates. A bedside ultrasound showed forceful cardiac contractions, which reduced the likelihood of cardiogenic pulmonary edema. Blood pressure continued to fall despite increasing doses of vasopressors. Family decided no further intervention and the patient expired. DISCUSSION: Pneumonia causes increased pulmonary vascular resistance; PEEP can improve oxygenation by recruiting alveoli, but at the expense of elevated intrathoracic pressures (ITP). In focal pathologies, PEEP paradoxically worsens ventilation-perfusion ratios and gas exchange.1 No set recommendations for ventilator management with worsening hypoxemia in right-to-left intrapulmonary shunting have been established.2 Airway pressure release ventilation decreases shunt fraction has been shown to improve V/Q matching, increase cardiac output, and decrease right atrial pressure by facilitating low airway pressure. Our patient’s rapid clinical decline prevented such attempts. CONCLUSIONS: When hypoxemia worsens paradoxically to increasing oxygenation maneuvers, clinicians should consider the possibility of right-to-left shunt. Reference #1: Annals of American Thoracic Society 11:2014 Reference #2: Respiratory Care 57:2012 DISCLOSURES: No relevant relationships by Sravya Brahmandam, source=Web Response no disclosure on file for Timothy Janz

The expression signature of very long non-coding RNA in myalgic encephalomyelitis/chronic fatigue syndrome

BackgroundMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic debilitating disease with huge social-economic impact. It has been suggested that immune dysregulation, nitrooxidative stress, and metabolic impairment might contribute to disease pathogenesis. However, the etiology of ME/CFS remains largely unclear, and diagnostic/prognostic disease markers are lacking. Several long noncoding RNAs (lncRNA, > 200 bp) have been reported to play roles in immunological diseases or in stress responses.MethodsIn our study, we examined the expression signature of 10 very long lncRNAs (> 5 kb, CR933609, His-RNA, AK124742, GNAS1-AS, EmX2OS, MIAT, TUG1, NEAT1, MALAT1, NTT) in the peripheral blood mononuclear cells of 44 ME/CFS patients.ResultsLncRNAs NTT, MIAT and EmX2OS levels were found to be significantly elevated in ME/CFS patients as compared with healthy controls. Furthermore, NTT and EmX2OS levels increased with disease severity. Stimulation of human monocytic cell line THP-1 and glioma cell line KALS1 with H2O2 (oxidative stress) and poly (I:C) (double strand RNA, representing viral activation) increased the expression levels of NTT and MIAT.ConclusionsOur study revealed a ME/CFS-associated very long lncRNA expression signature, which might reflect the regulatory response in ME/CFS patients to oxidative stress, chronic viral infection and hypoxemia. Further investigations need to be done to uncover the functions and potential diagnostic value of these lncRNAs in ME/CFS.

Peculiarities of glucose intake in fetal tissues in chronic hypoxemia

Objective — to investigate fetal blood distribution and glucose metabolism of heart, liver and brain during chronic hypoxaemia. Establishment of a model of real time measurement of the metabolic changes during chronic fetal hypoxaemia using PET-CT measurement in pregnant sheep after iatrogenic induction of chronic fetal hypoxaemia. Laser coagulation of placental vessels was performed in pregnant sheep in order to cause fetal hypoxaemia 14 days before the PET-procedure. The following PET-Scans were performed after 18F-FDG was injected into the jugular vein of the sheep. Fetal glucose uptake was scanned in fetal brain, liver, heart and kidneys during a period of 60 min after injection of the FDG tracer. Glucose uptake of these organs was measured in comparison with placental glucose uptake during the above-called 60 minutes course. Here we present the analysis of the metabolic changes in fetal hypoxaemia in a small series of 8 fetal sheep. It was found that FDG Uptake in the placenta, brain, liver and heart of the fetus was measured at normal oxygenation and in chronic hypoxia in 8 sheep fetuses, between 112 and 135 days of pregnancy (gestational age) 125±4 days (mean±SD). Umbilical cord artery resistance was significantly higher in hypoxemic fetuses compared to normoxemic. Venous duct reactions as a respond to hypoxia was observed. Index of pulsation in the umbilical artery was not significantly increased during hypoxia (1,06±0,18 та 1,67±0,12, р=0,018). PI in venous duct during chronic hypoxia (0,62±0,25) was increased in compare with normoxemic (0,41±0,2), but not significantly. Relative FDG uptake was about 3.8 times higher in brain of hypoxemic fetuses (0.019±0.005) compared to normoxemic (0.005±0.002), (р=0,02). In contrast, hypoxic fetal heart showed no significant difference in absorption of FDG compared to normoxemic fetal brain (p=0.11). Relative FDG uptake in the liver did not differ substantially between the two groups (p=0.97). Thus, it was shown that chronic maternal hypoxemia led to decreased placental and increased brain blood flow, although, glucose metabolism was not decreased in the fetal liver and heart.