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2022 ◽  
Zixuan Liu ◽  
Mingming Chen ◽  
Yini Sun ◽  
Xu Li ◽  
Liu Cao ◽  

Heparin-binding protein (HBP), as a granule protein secreted by polymorphonuclear neutrophils (PMNs) participates in the pathophysiological process of sepsis. It has been reported that HBP is a biomarker of sepsis, which is related to the severity of septic shock and organ dysfunction. HBP binds to vascular endothelial cells as one of the primary target sites. However, it is still unclear whether HBP-binding protein receptors exist on the surface of ECs. The effect of HBP on vascular permeability in sepsis and its mechanism needs to be explored. We conducted in vivo and in vitro study. We demonstrated that HBP bound to transforming growth factor-β receptor type 2 (TGF-β-R2) as a ligand. GST pull-down analysis reveals that HBP mainly interacts with the extracellular domain of TGF-β-R2. HBP induced acute lung injury (ALI) and vascular leakage via activation of TGF-β/SMAD2/3 signaling pathway. Permeability assay suggests TGF-β-R2 is necessary for HBP-induced increased permeability. We also defined the role of HBP and its potential membrane receptor TGF-β-R2 in the blood-gas barrier in the pathogenesis of HBP-related ALI.

2022 ◽  
Vol 12 ◽  
Laura Warner ◽  
Annika Bach-Hagemann ◽  
Walid Albanna ◽  
Hans Clusmann ◽  
Gerrit A. Schubert ◽  

Objective: Impaired cerebral blood flow (CBF) regulation, such as reduced reactivity to hypercapnia, contributes to the pathophysiology after aneurysmal subarachnoid hemorrhage (SAH), but temporal dynamics in the acute phase are unknown. Featuring comparable molecular regulation mechanisms, the retinal vessels participate in chronic and subacute stroke- and SAH-associated vessel alterations in patients and can be studied non-invasively. This study is aimed to characterize the temporal course of the cerebral and retinal vascular reactivity to hypercapnia in the acute phase after experimental SAH and compare the potential degree of impairment.Methods: Subarachnoid hemorrhage was induced by injecting 0.5 ml of heparinized autologous blood into the cisterna magna of male Wistar rats using two anesthesia protocols [isoflurane/fentanyl n = 25 (Sham + SAH): Iso—Group, ketamine/xylazine n = 32 (Sham + SAH): K/X—Group]. CBF (laser speckle contrast analysis) and physiological parameters were measured continuously for 6 h. At six predefined time points, hypercapnia was induced by hypoventilation controlled via blood gas analysis, and retinal vessel diameter (RVD) was determined non-invasively.Results: Cerebral reactivity and retinal reactivity in Sham groups were stable with only a slight attenuation after 2 h in RVD of the K/X—Group. In the SAH Iso—Group, cerebral and retinal CO2 reactivity compared to baseline was immediately impaired starting at 30 min after SAH (CBF p = 0.0090, RVD p = 0.0135) and lasting up to 4 h (p = 0.0136, resp. p = 0.0263). Similarly, in the K/X—Group, cerebral CO2 reactivity was disturbed early after SAH (30 min, p = 0.003) albeit showing a recovery to baseline after 2 h while retinal CO2 reactivity was impaired over the whole observation period (360 min, p = 0.0001) in the K/X—Group. After normalization to baseline, both vascular beds showed a parallel behavior regarding the temporal course and extent of impairment.Conclusion: This study provides a detailed temporal analysis of impaired cerebral vascular CO2 reactivity starting immediately after SAH and lasting up to 6 h. Importantly, the retinal vessels participate in these acute changes underscoring the promising role of the retina as a potential non-invasive screening tool after SAH. Further studies will be required to determine the correlation with functional outcomes.

2022 ◽  
Vol 2022 ◽  
pp. 1-10
Vasileios Panoulas ◽  
Charles Ilsley

Introduction. We aimed to identify the independent “frontline” predictors of 30-day mortality in patients with acute coronary syndromes (ACS) and propose a rapid cardiogenic shock (CS) classification and management pathway. Materials and Methods. From 2011 to 2019, a total of 11439 incident ACS patients were treated in our institution. Forward conditional logistic regression analysis was performed to determine the “frontline” predictors of 30 day mortality. The C-statistic assessed the discriminatory power of the model. As a validation cohort, we used 431 incident ACS patients admitted from January 1, 2020, to July 20, 2020. Results. Independent predictors of 30-day mortality included age (OR 1.05; 95% CI 1.04 to 1.07, p < 0.001 ), intubation (OR 7.4; 95% CI 4.3 to 12.74, p < 0.001 ), LV systolic impairment (OR severe_vs_normal 1.98; 95% CI 1.14 to 3.42, p = 0.015 , OR moderate_vs_normal 1.84; 95% CI 1.09 to 3.1, p = 0.022 ), serum lactate (OR 1.25; 95% CI 1.12 to 1.41, p < 0.001 ), base excess (OR 1.1; 95% CI 1.04 to 1.07, p < 0.001 ), and systolic blood pressure (OR 0.99; 95% CI 0.982 to 0.999, p = 0.024 ). The model discrimination was excellent with an area under the curve (AUC) of 0.879 (0.851 to 0.908) ( p < 0.001 ). Based on these predictors, we created the SAVE (SBP, Arterial blood gas, and left Ventricular Ejection fraction) ACS classification, which showed good discrimination for 30-day AUC 0.814 (0.782 to 0.845) and long-term mortality p log − rank < 0.001 . A similar AUC was demonstrated in the validation cohort (AUC 0.815). Conclusions. In the current study, we introduce a rapid way of classifying CS using frontline parameters. The SAVE ACS classification could allow for future randomized studies to explore the benefit of mechanical circulatory support in different CS stages in ACS patients.

Genes ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 132
Mathilde Filser ◽  
Betty Gardie ◽  
Mathieu Wemeau ◽  
Patricia Aguilar-Martinez ◽  
Muriel Giansily-Blaizot ◽  

High oxygen affinity hemoglobin (HOAH) is the main cause of constitutional erythrocytosis. Mutations in the genes coding the alpha and beta globin chains (HBA1, HBA2 and HBB) strengthen the binding of oxygen to hemoglobin (Hb), bringing about tissue hypoxia and a secondary erythrocytosis. The diagnosis of HOAH is based upon the identification of a mutation in HBA1, HBA2 or HBB in specialized laboratories. Phenotypic studies of Hb are also useful, but electrophoretic analysis can be normal in 1/3 of cases. The establishment of the dissociation curve of Hb can be used as another screening test, a shift to the left indicating an increased affinity for Hb. The direct measurement of venous P50 using a Hemox Analyzer is of great importance, but due to specific analytic conditions, it is only available in a few specialized laboratories. Alternatively, an estimated measurement of the P50 can be obtained in most of the blood gas analyzers on venous blood. The aim of our study was therefore to determine whether a normal venous P50 value could rule out HOAH. We sequenced the HBB, HBA1 and HBA2 genes of 75 patients with idiopathic erythrocytosis. Patients had previously undergone an exhaustive medical check-up after which the venous P50 value was defined as normal. Surprisingly, sequencing detected HOAH in three patients (Hb Olympia in two patients, and Hb St Nazaire in another). A careful retrospective examination of their medical files revealed that (i) one of the P50 samples was arterial; (ii) there was some air in another sample; and (iii) the P50 measurement was not actually done in one of the patients. Our study shows that in real life conditions, due to pre-analytical contingencies, a venous P50 value that is classified as being normal may not be sufficient to rule out a diagnosis of HOAH. Therefore, we recommend the systematic sequencing of the HBB, HBA1 and HBA2 genes in the exploration of idiopathic erythrocytosis.

2022 ◽  
Vol 22 (1) ◽  
Meenu Pandey ◽  
Mark D. Lyttle ◽  
Katrina Cathie ◽  
Alasdair Munro ◽  
Thomas Waterfield ◽  

Abstract Background Point-of-care testing (POCT) is diagnostic testing performed at or near to the site of the patient. Understanding the current capacity, and scope, of POCT in this setting is essential in order to respond to new research evidence which may lead to wide implementation. Methods A cross-sectional online survey study of POCT use was conducted between 6th January and 2nd February 2020 on behalf of two United Kingdom (UK) and Ireland-based paediatric research networks (Paediatric Emergency Research UK and Ireland, and General and Adolescent Paediatric Research UK and Ireland). Results In total 91/109 (83.5%) sites responded, with some respondents providing details for multiple units on their site based on network membership (139 units in total). The most commonly performed POCT were blood sugar (137/139; 98.6%), urinalysis (134/139; 96.4%) and blood gas analysis (132/139; 95%). The use of POCT for Influenza/Respiratory Syncytial Virus (RSV) (45/139; 32.4%, 41/139; 29.5%), C-Reactive Protein (CRP) (13/139; 9.4%), Procalcitonin (PCT) (2/139; 1.4%) and Group A Streptococcus (5/139; 3.6%) and was relatively low. Obstacles to the introduction of new POCT included resources and infrastructure to support test performance and quality assurance. Conclusion This survey demonstrates significant consensus in POCT practice in the UK and Ireland but highlights specific inequity in newer biomarkers, some which do not have support from national guidance. A clear strategy to overcome the key obstacles of funding, evidence base, and standardising variation will be essential if there is a drive toward increasing implementation of POCT.

2022 ◽  
pp. 1-12
Dong Xing ◽  
Li Chen ◽  
Lantao Wang ◽  
Jing Jin ◽  
Dong Liu ◽  

BACKGROUND: Stereotactic radiotherapy (SBRT) is widely used in the treatment of thoracic cancer. OBJECTIVE: To evaluate the efficacy of a non-rebreather mask (NRBM) and high-flow nasal cannula (HFNC) in patients with radiation pneumonia complicated with respiratory failure. METHODS: This was a single-center randomized controlled study. Patients admitted to the EICU of the Fourth Hospital of Hebei Medical University were selected and divided into NRBM and HFNC group. Arterial blood gas analysis, tidal volume, respiratory rates and the cases of patients receiving invasive assisted ventilation were collected at 0, 4, 8, 12, 24, 48, and 72 h after admission. RESULTS: (1) The PaO2/FiO2, respiratory rates, and tidal volume between the two groups at 0, 4, 8, 12, 24, 48, and 72 h were different, with F values of 258.177, 294.121, and 134.372, all P< 0.01. These indicators were different under two modes of oxygenation, with F values of 40.671, 168.742, and 55.353, all P< 0.01, also varied with time, with an F value of 7.480, 9.115, and 12.165, all P< 0.01. (2) The incidence of trachea intubation within 72 h between HFNC and NRBM groups (23 [37.1%] vs. 34 [54.0%], P< 0.05). The transition time to mechanical ventilation in the HFNC and NRBM groups (55.3 ± 3.2 h vs. 45.9 ± 3.6 h, P< 0.05). (3) The risk of intubation in patients with an APACHE-II score > 23 was 2.557 times than score ⩽ 23, and the risk of intubation in the NRBM group was 1.948 times more than the HFNC group (P< 0.05). CONCLUSION: Compared with the NRBM, HFNC can improve the oxygenation state of patients with radiation pneumonia complicated with respiratory failure in a short time, and reduce the incidence of trachea intubation within 72 h.

2022 ◽  
Vol 2 (1) ◽  
pp. 47-61
Kiichi Hirota ◽  
Taku Mayahara ◽  
Yosuke Fujii ◽  
Kenichiro Nishi

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a pandemic and caused a huge burden to healthcare systems worldwide. One of the characteristic symptoms of COVID-19 is asymptomatic hypoxemia, also called happy hypoxia, silent hypoxemia, or asymptomatic hypoxemia. Patients with asymptomatic hypoxemia often have no subjective symptoms, such as dyspnea, even though hypoxemia is judged by objective tests, such as blood gas analysis and pulse oximetry. Asymptomatic hypoxemia can lead to acute respiratory distress syndrome, and the delay in making a diagnosis and providing initial treatment can have fatal outcomes, especially during the COVID-19 pandemic. Thus far, not many studies have covered asymptomatic hypoxemia. We present a review on the human response to hypoxemia, focusing on the respiratory response to hypoxemia rather than the pathophysiology of lung injury arising from SARS-CoV-2 infection. We have also discussed whether asymptomatic hypoxemia is specific to SARS-CoV-2 infection or a common phenomenon in lung-targeted viral infections.

Alireza Saliminia ◽  
Fatemeh Golpayegani

Background: The occurrence of bleeding during major surgeries is common and requires timely and accurate management in the prevention and treatment of hypovolemia and hemodynamic instability during and after surgery. This study evaluated the correlation and agreement between the two protocols determining the status of the hypovolemia during hysterectomy. Methods: This study was a randomized single-blinded clinical trial. The study population included 30 patients undergoing Total Abdominal Hysterectomy in Shariati Hospital in Tehran between 2015 and 2016. The patients were randomly assigned to two groups using a randomized table of numbers, so that in the FTc group, fluid therapy was performed based on the FTc index and in the PVI group based on the PVI index. The changes in FTc and PVI values were recorded every 5 minutes and the changes in the two indicators from the beginning to the end of the treatment were evaluated. At the beginning and end of the surgery, an arterial blood gas analysis (ABG) was also performed. The amount of bleeding during operation and urinary output were recorded in two groups. Results: There was no significant difference across the two groups in total fluid intake during surgery, mean volume of blood loss, mean urine output, and duration of surgery. The arterial blood gas status was also similar in both groups at the beginning and the end of the operation. We found a strong adverse correlation between FTC and PVI indices at the different time points evaluated within the surgery. In total, there was a strong correlation between the mean FTC and the mean PVI during the first hour (r=-0.765, P < 0.001) and the second hour (r=-0.941, -P < 0.001) of operation. Considering the cut-off point of 350msec for the FTC and 13% for the PVI in predicting hypovolemia, the agreement between the two protocols in fluid therapy during the first hour after surgery was 79.8% and 76.6%. Conclusion: There is a strong and significant correlation between the two FTC (with a cut off of 350) and PVI (with a cut point of 13%) to predict need for fluid therapy.

Nazlıhan Boyacı ◽  
Sariyya Mammadova ◽  
Nurgül Naurizbay ◽  
Merve Güleryüz ◽  
Kamil İnci ◽  

Background: Transcutaneous partial pressure of carbon dioxide (PtCO2) monitorization provides a continuous and non-invasive measurement of partial pressure of carbon dioxide (pCO2). In addition, peripheral oxygen saturation (SpO2) can also be measured and followed by this method. However, data regarding the correlation between PtCO2 and arterial pCO2 (PaCO2) measurements acquired from peripheric arterial blood gas is controversial. Objective: We aimed to determine the reliability of PtCO2 with PaCO2 based on its advantages, like non-invasiveness and continuous applicability. Methods: Thirty-five adult patients with hypercapnic respiratory failure admitted to our tertiary medical intensive care unit (ICU) were included. Then we compared PtCO2 and PaCO2 and both SpO2 measurements simultaneously. Thirty measurements from the deltoid zone and 26 measurements from the cheek zone were applied. Results: PtCO2 could not be measured from the deltoid region in 5 (14%) patients. SpO2 and pulse rate could not be detected at 8 (26.7%) of the deltoid zone measurements. Correlation coefficients between PtCO2 and PaCO2 from deltoid and the cheek region were r: 0,915 and r: 0,946 (p = 0,0001). In comparison with the Bland-Altman test, difference in deltoid measurements was -1,38 ± 1,18 mmHg (p = 0.252) and in cheek measurements it was -5,12 ± 0,92 mmHg (p = 0,0001). There was no statistically significant difference between SpO2 measurements in each region. Conclusion: Our results suggest that PtCO2 and SpO2 measurements from the deltoid region are reliable compared to the arterial blood gas analysis in hypercapnic ICU patients. More randomized controlled studies investigating the effects of different measurement areas, hemodynamic parameters, and hemoglobin levels are needed.

Children ◽  
2022 ◽  
Vol 9 (1) ◽  
pp. 46
Srinivasan Mani ◽  
Praveen Chandrasekharan

Staphylococcus lugdunensis is a rare cause of late-onset sepsis in preterm infants. To our best knowledge, we report the fourth case of a male preterm infant who developed fulminant late-onset sepsis due to Staphylococcus lugdunensis with persistent bacteremia secondary to an infected aortic thrombus confirmed with two positive blood cultures. Our patient was an extremely low birth weight growth-restricted infant born at 27 weeks gestation and initially required an umbilical arterial catheter for blood pressure and blood gas monitoring. The course of this neonate was complicated by severe respiratory distress syndrome that evolved into chronic lung disease along with multiple episodes of tracheitis. Hemodynamically, the infant had a significant patent ductus arteriosus, and an episode of medical necrotizing enterocolitis followed by Staphylococcus lugdunensis septicemia. He was diagnosed with an infected aortic thrombus, probably the occult focus responsible for the persistent bacteremia. After a 6-week course of intravenous antibiotics and 4-week course of anticoagulant therapy, the infant responded and recovered without complications.

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