Lower Blood pH Research Articles

The role of neutrophilia in hyperlactatemia, blood acidosis, impaired oxygen transport, and mortality outcome in critically ill COVID-19 patients.

COVID-19 severity and high in-hospital mortality are often associated with severe hypoxemia, hyperlactatemia, and acidosis, yet the key players driving this association remain unclear. It is generally assumed that organ damage causes toxic acidosis, but since neutrophil numbers in severe COVID-19 can exceed 80% of the total circulating leukocytes, we asked if metabolic acidosis mediated by the glycolytic neutrophils is associated with lung damage and impaired oxygen delivery in critically ill patients. Based on prospective mortality outcome, critically ill COVID-19 patients were divided into ICU- survivors and ICU-non-survivors. Samples were analyzed to explore if correlations exist between neutrophil counts, lung damage, glycolysis, blood lactate, blood pH, hemoglobin oxygen saturation, and mortality outcome. We also interrogated isolated neutrophils, platelets, and PBMCs for glycolytic activities. Arterial blood gas analyses showed remarkable hypoxemia in non-survivors with no consistent differences in PCO2 or [HCO3 -]. The hemoglobin oxygen dissociation curve revealed a right-shift, consistent with lower blood-pH and elevated blood lactate in non-survivors. Metabolic analysis of different blood cells revealed increased glycolytic activity only when considering the total number of neutrophils. This indicates the role of neutrophilia in hyperlactatemia and lung damage, subsequently contributing to mortality outcomes in severe SARS-CoV-2 infection.

An investigation into the contributing factors to survival of ARDS patients supported by veno-venous ECMO.

This study aimed to identify characteristics associated with survival during and post Extra Corporeal Membrane Oxygenation (ECMO) therapy, in patients with acute respiratory distress syndrome (ARDS) during the COVID-19 pandemic. A retrospective observational study on 94 consecutive patients with confirmed COVID-19 induced ARDS supported by ECMO was carried out 49/94 (52.7%) patients survived to hospital discharge. Non-survivors were found to have significantly (p < .05) higher: Pre-ECMO International normalized ratios (INR), carbon dioxide partial pressure (pCO2), Acute Kidney Injury (AKI) scores and blood urea levels. Also, lower pre-ECMO peak inspiratory pressures (PIP), mean arterial pressure, saturation of arterial oxygen (SaO2), blood bicarbonate levels (HCO3), blood Ph and fewer trials off ECMO with shorter combined trial off times. Patients that did not survive were more likely to have renal impairment and have received peri-ECMO haemofiltration. Poor prognosis was significantly associated with: receiving pre-ECMO nitric oxide (HR = 3.047, CI = 1.247-7.447, p = .015), renal impairment (HR = 3.023, CI = 1.586-5.763, p < .001), AKI of 2 (HR = 3.611, CI = 1.382-9.441, p = .009) or 3 (HR = 3.275, CI = 1.235-8.685, p = .017), peri-ECMO haemofiltration (HR = 2.412, CI = 1.310-4.442, p = .005) and the ABO blood group B (HR = 3.103, CI = 1.335-7.212, p = .008). pre-ECMO high CO2 (HR = 1.134, CI = 1.031-1.248, p = .010), blood lactate (HR = 1.350, CI = 1.156-1.576, p < .001), INR (HR = 2.571, CI = 1.438-4.598, p=<0.001) and lower blood Ph (HR = 0.023, CI = 0.002-0.210, p < .001). Commonly used mortality scores may not be of use in a COVID-19 cohort of ECMO patients. The initiation of ECMO needs to be implemented prior to metabolic derangements, renal and fulminant respiratory failure.

Risk Factors for INtubation-SURfactant-Extubation Failure in Infants With Neonatal Respiratory Distress Syndrome

To identify clinical characteristics predictive of failure or success of the INtubation-SURfactant-Extubation (INSURE) strategy, to distinguish infants who could be managed using this strategy to prevent mechanical ventilation (MV). Infants with a gestational age <32 weeks were classified into two groups according to whether they required reintubation and MV within 72 h after birth. The clinical characteristics of the two groups were subsequently analyzed. INSURE was unsuccessful in 77 infants (20.7%). Infants in the INSURE failure group had a higher incidence of severe respiratory distress syndrome, as evidenced by radiological grade; lower blood pH, partial oxygen pressure, and base excess (BE) levels; higher partial carbon dioxide pressure levels at the first arterial blood gas analysis; lower Apgar scores at 1 and 5 min; lower use of antenatal steroids; and higher occurrence of gestational diabetes mellitus, versus those in the INSURE success group. Multiple regression analysis confirmed severe radiological grade, lower BE levels at the first arterial blood gas analysis, and decreased use of antenatal steroids as independent risk factors for INSURE failure. Compared with infants in the INSURE success group, those in the INSURE failure group also had higher mortality. We successfully identified specific predictors of an unsuccessful INSURE strategy. Maintaining high-risk preterm infants with one or several predictors intubated and treated with MV after surfactant administration can prevent reintubation and reduce mortality.

Insights into the baseline blood pH homeostasis at admission and the risk of in-hospital mortality in COVID-19 patients.

Aim: A laboratory finding in critically ill COVID-19 patients is blood academia (pH <7.35). We investigated its cause in connection with the admission baseline blood pH homeostasis.Patients & methods: We retrospectively monitored the baseline blood pH homeostasis of 1215 COVID-19 patients who were admitted with pneumonia using data-driven knowledge. Two categories of patients were identified: non-survivors (107) and survivors (1108).Results: Non-survivors showed greater levels of lactate and lower blood pH, saturation, and partial pressure of oxygen than survivors. A bivariate Spearman's correlation matrix showed that the [HCO3-]/pCO2 and pCO2 of non-survivors exhibited an unmatched connection, but not in the survivor group. When comparing non-survivors to survivors, the dendrograms derived from the bivariate comparison matrix showed differences in gasometry parameters like blood pH, [HCO3-]/pCO2 ratio, anion gap and pO2.Conclusion: The little variations in the gasometry readings between survivors and non-survivors upon admission suggested abnormal changes in the complementary renal and respiratory systems that bring blood pH back to normal. In advanced COVID-19, modest blood acid-base imbalances could become blood acidemia if these compensatory strategies were overused. Data-driven monitoring of acid-base parameters may help predict abnormal blood pH and the advancement of metabolic acidemia before it is too late.

Clinical Profile and Outcome of Severe Acute Respiratory Illness (SARI) in Children Amidst the COVID-19 Pandemic.

Beginning in December 2019, COVID-19 rapidly emerged as a global pandemic. Though its severity in children was reported to be less than that in adults, data on its epidemiology in relation to severe acute respiratory illness (SARI) caused by other microbes needed to be generated. This study compares theclinical profile and outcome of children hospitalized with COVID-19-positive and negative SARI. This is a prospective observational analytical study involving children 1 month to 18 years old, hospitalized with COVID-19-positive and negative SARI during the pandemic. All eligible patients were enrolled after obtaining informed parental consent. Their clinical manifestations, investigations, and outcomes were documented on a predesigned case record form. A nasopharyngeal swab sample for COVID-19 reverse transcription polymerase chain reaction was sent, and results were noted. From May 2020 to July 2021, 267 children were hospitalized with a diagnosis of SARI. Out of these, 146 (54.7%) were boys and 78.7% were under five years of age. Other presentations included fever and cough, breathlessness, nausea, vomiting, diarrhea, rash, seizures, and altered sensorium. Twenty-eight patients (10.5%) tested positive for COVID-19. COVID-19 patients were similar in terms of demographic characteristics and presenting symptoms to non-COVID-19 patients but had a lower absolute lymphocyte count (p = 0.019) and higher serum alanine transaminase levels (p = 0.013). Acute respiratory distress syndrome (OR, 4.3; 95% CI, 1.8-10.0),shock (OR, 3.9; 95% CI, 1.9-7.9), and need for intensive care unit admission (OR, 9.9; 95% CI, 6.9-14) were more common in COVID-19 SARI patients. Death occurred in 18% of COVID-19 and 9% of non-COVID-19 patients (p = 0.07). SARI nonsurvivors had significantly lower blood pH and platelet counts than survivors. Comparison of COVID-19-positive and negative SARI patients showed subtle differences between the two groups, with COVID-19-positive children having an increased severity of illness. Also, laboratory evidence of multiorgan dysfunction at admission was associated with higher mortality.

Impact of perinatal factors on meconium aspiration syndrome in full-term newborns and the construction of a column chart prediction model: An observational study.

To explore the influence of perinatal-related factors on meconium aspiration syndrome (MAS) in full-term neonates and construct a nomogram prediction model for risk stratification of neonatal MAS and adoption of preventive measures. A total of 424 newborns and their mothers who were regularly examined at our hospital between January 2020 and December 2023 who had meconium-contaminated amniotic fluid during delivery were retrospectively selected as participants. Neonates were divided into MAS and non-MAS groups based on whether MAS occurred within 3 days after birth. Data from the 2 groups were analyzed, and factors influencing MAS were screened using multivariate logistic regression analysis. The R3.4.3 software was used to construct a nomogram prediction model for neonatal MAS risk. Receiver operating characteristic (ROC) curve analysis and the Hosmer-Lemeshow goodness-of-fit test were used to evaluate the performance of the model, and its clinical effectiveness was evaluated using a decision curve. Among the 424 neonates with meconium-stained amniotic fluid, 51 developed MAS within 3 days of birth (12.03%). Multivariate logistic regression analysis showed that a low amniotic fluid index before delivery (OR = 2.862, P = .019), advanced gestational age (OR = 0.526, P = .034), cesarean section (OR = 2.650, P = .013), severe amniotic fluid contamination (OR = 4.199, P = .002), low umbilical cord blood pH (OR = 2.938, P = .011), and low neonatal Apgar 1-min score (OR = 3.133, P = .006) were influencing factors of MAS in full-term neonates. Based on the above indicators, a nomogram prediction model for MAS risk of full-term newborns was constructed. The area under the ROC curve of the model was 0.931. The model was also tested for goodness-of-fit deviation (χ2 = 3.465, P = .903). Decision curve analysis found that the model was clinically effective in predicting the net benefit of MAS risk in neonates with meconium-stained amniotic fluid. The construction of a column chart prediction model for neonatal MAS risk based on prenatal amniotic fluid index, gestational age, delivery method, amniotic fluid contamination level, newborn umbilical blood pH value, and Apgar 1-min score has a certain application value.

AKAP2 plays a pivotal role in renal acid-base homeostasis during metabolic acidosis

Reversible phosphorylation and dephosphorylation of kidney proteins modulate their activities and localization and play a central role in maintaining fluid and acid-base homeostasis. The proximal tubule and the intercalated cells of the nephron are main sites of acid-base balance. It was previously demonstrated that some kidney transporters involved in the pH homeostasis were regulated by the c-AMP/Protein Kinase A (PKA) signaling pathway.The A-Kinase anchoring protein 2 (AKAP2), is a scaffold protein that binds to the Protein Kinase A (PKA) allowing the phosphorylation of target proteins but is also known to interact with Protein Phosphatase 1 and consequently contributes to protein dephosphorylation. In this study, we hypothesize that AKAP2 regulates the activity and localization of renal transporters during metabolic acidosis. An inducible and nephron-specific Akap2Pax8/LC1 knockout mouse model was generated. Fluorescent immunostaining showed that AKAP2 is present in the tubules mainly at the apical plasma membrane. AKAP2 knock-out mice in normal conditions presented an acidic urine pH and polyuria compared to control mice. Ex-vivo data from micro-perfused CCDs demonstrated a higher Na+ reabsorption and K+ secretion in AKAP2 KO mice. This suggests its importance in maintaining acid-base balance even under physiological conditions. Moreover, when treated with an ammonium chloride diet, KO mice were sensitive to the acid load; showed a lower blood pH, hyperchloremia, a lower bicarbonate level and a two-fold higher blood ammonia. The sensitivity of the KO mice further supports the role of AKAP2 in acid-base homeostasis. Although we think this is due to renal acid-base transporters activity deregulation, the consideration of a potential defect in water reabsorption mechanisms contributing to acidosis is also valid. Our study provides valuable insights into the role of AKAP2 in maintaining fluid and acid-base homeostasis in the kidneys. The findings open avenues for further research into the molecular mechanisms underlying AKAP2-mediated regulation of renal transporters and its impact on acid-base balance. Swiss National Science Foundation (SNSF). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Mortality rates among adult critical care patients with unusual or extreme values of vital signs and other physiological parameters: a retrospective study.

We evaluated relationships of vital signs and laboratory-tested physiological parameters with in-hospital mortality, focusing on values that are unusual or extreme even in critical care settings. We retrospectively studied Philips Healthcare-MIT eICU data (207 U.S. hospitals, 20142015), including 166,959 adult-patient critical care admissions. Analyzing most-deranged (worst) value measured in the first admission day, we investigated vital signs (body temperature, heart rate, mean arterial pressure, and respiratory rate) as well as albumin, bilirubin, blood pH via arterial blood gas (ABG), blood urea nitrogen, creatinine, FiO2 ABG, glucose, hematocrit, PaO2 ABG, PaCO2 ABG, sodium, 24-hour urine output, and white blood cell count (WBC). In-hospital mortality was ≥50% at extremes of low blood pH, low and high body temperature, low albumin, low glucose, and low heart rate. Near extremes of blood pH, temperature, glucose, heart rate, PaO2 , and WBC, relatively. Small changes in measured values correlated with several-fold mortality rate increases. However, high mortality rates and abrupt mortality increases were often hidden by the common practice of thresholding or binning physiological parameters. The best predictors of in-hospital mortality were blood pH, temperature, and FiO2 (scaled Brier scores: 0.084, 0.063, and 0.049, respectively). In-hospital mortality is high and sharply increasing at extremes of blood pH, body temperature, and other parameters. Common-practice thresholding obscures these associations. In practice, vital signs are sometimes treated more casually than laboratory-tested parameters. Yet, vitals are easier to obtain and we found they are often the best mortality predictors, supporting perspectives that vitals are undervalued.

Клинико-лабораторные факторы риска рецидива (реактивации) ретинопатии недоношенных после интравитреального введения афлиберцепта

Purpose. To study the causes of reactivation of retinopathy of prematurity (ROP) after intravitreal aflibercept injections. Material and methods. This study was carried out at V.F. Voino-Yasenetsky Scientific and Practical Center for Specialized Medical Care in Children from September 2021 to February 2023. The study included 101 premature infants (202 eyes) with retinopathy of prematurity who received intravitreal administration of aflibercept. The patients were divided into two groups: the control group included patients who received a single intravitreal injection of a VEGF inhibitor (aflibercept) with a positive effect. The main group included children who received two or more intravitreal injections of VEGF inhibitors (aflibercept) after reactivation of ROP. All patients were monitored for reactivation of retinopathy of prematurity after intravitreal injection of aflibercept. Results. The study noted a statistically significant difference in blood pH levels, stage of ROP, and APROP. In the group with reactivation ROP, APROP was noted 2 times more often (48.94% versus 27.78% in the control group). The group with more intravitreal aflibercept injections had lower blood pH levels (7.348±0.044 versus 7.372±0.030 in the control group). Conclusion. The study showed that clinical and paraclinical risk factors for the development of recurrent (reactivation) of ROP after intravitreal treatment with aflibercept are: severe eye disease (stage of ROP, aggressive posterior ROP), a change in the acid-base balance of the blood towards increased acidity. Blood acidity reflects a generalized process of impaired angiogenesis throughout the body. The more severe the patient’s initial eye condition, the higher the incidence of reactivation of ROP. Key words: recurrence, reactivation, retinopathy of prematurity, risk factor, clinical and paraclinical, aflibercept

Assessment of the Correlation Between Arterial Blood Gas Indices and Duration of Stay in the Emergency Department Observation Unit for Pediatric Patients Aged 0-18 with Rotavirus Gastroenteritis

Purpose: Rotavirus (RV) is the predominant pathogen responsible for the onset of infectious acute gastroenteritis among children younger than five years of age, which is one of the important public health concerns and one of the childhood gastroenteritis that can cause morbidity and mortality. Although definitive diagnostic methods are important in such cases, these methods are not always easily accessible. That study aims to investigate the association between blood gas parameters in respondents who have tested positive for RV antigen and their subsequent observation time in the emergency department as well as the length of their hospitalization. Materials and methods: In this retrospective analysis encompassed 237 individuals ranging from 0 to 18 years old who sought medical attention at the outpatient clinic or emergency department of Adiyaman University Faculty of Medicine Training and Research Hospital and were found to have a positive RV antigen test. Respondents were segregated into cohorts in accordance with age, gender, blood gas parameters, hemogram, biochemical parameters, duration of stay in the emergency observation room, and duration of stay in the pediatric ward. The respondents were categorized based on various criteria including age, sex, blood gas readings, complete blood count, biochemical markers, duration of stay in the emergency observation area, and hospitalization period in the pediatric unit. Comprehensive demographic, blood gas, hematologic, and biochemical data were compiled and analyzed employing SPSS version 22.0. Results: The study identified significant differences in the pH, pO2, and HCO3 levels, along with the mean platelet volume (MPV) among the participants. Notably, a significant correlation was established between the pH levels of blood gases in the emergency room observation space and the observation span for respondents testing positive for RV, whereas no significant link was observed between blood gas values and the duration of hospital stay. Conclusion: The findings suggest that while blood gas analysis outcomes may not predict hospitalization length in cases of Rotavirus gastroenteritis, respondents presenting with lower blood pH levels tend to spend less time in the emergency observation unit. Therefore, it is recommended that blood gas analysis be conducted routinely for respondents presenting with symptoms of Rotavirus gastroenteritis upon their arrival at the emergency medical services.

Abstract 17295: In Situ Recovery of Multiple Organs Using Venoarterial ECMO in a Murine Model of Uncontrolled DCD

Introduction: The utilization of extracorporeal membrane oxygenation (ECMO) for Donation after Circulatory Death (DCD) can substantially increase the donor pool, organ yield per donor, and organ shelf life. Clinical attempts to recover organs for transplantation after uncontrolled DCD are very complex and hard to reproduce. As a preliminary strategy for completing this endeavor, experimental protocols employing feasible animal models are strongly recommended. Hypothesis: The objective of the investigation was to develop a mouse model of ECMO-based cadaver management protocol for uncontrolled DCD donation after "out-of-hospital" death. Methods: Following 10 min after confirmed death, murine cadavers (C57BL/6 background) were administered with heparin-streptokinase and cannulated for veno-arterial ECMO. Cadaver bodies were connected to a murine ECMO machine 1 h post-mortem and subjected to extracorporeal circulation for subsequent 2 hrs. Blood gas parameters, cardiac activity, and general organ state were assessed using BGA analysis, ECG, and histology, accordingly. We have designed and incorporated into an ECMO circuit a previously unreported, miniaturized murine hemodialysis for the treatment of severe hyperkalemia and metabolic acidosis that arose following death. Results: Control BGA parameters recorded 1 h after death were incompatible with normal physiology: extremely low blood pH, profound negative base excess, and extraordinarily high lactate and K + levels. Two hours after ECMO support, blood pH values of a cadaver body restored from &lt;6.5 to 7.3 ± 0.05, pCO 2 was lowered from &gt;130 to 41.7 ± 10.5 mmHg, sO2, base excess, and HCO 3 were all elevated from below detection thresholds to 99.5 ± 0.6%, -4 ± 6.2 and 22.0 ± 6.0 mmol/L, respectively (Student T-test, p &lt; 0.05). The implementation of hemodialysis resulted in a significant decrease in both hyperlactatemia and hyperkalemia. Conclusions: Our model presents novel opportunities for the management of cadaver organs in order to promote uncontrolled DCD donation, thereby contributing to the resolution of the organ shortage problem. Our approach enables the implementation of a variety of modern blood purification techniques in cadaveric organ recovery using ECLS.

Generation of Atp6v1g3-Cre mice for investigation of intercalated cells and the collecting duct.

Kidney intercalated cells (ICs) maintain acid-base homeostasis and recent studies have demonstrated that they function in the kidney's innate defense. To study kidney innate immune function, ICs have been enriched using vacuolar ATPase (V-ATPase) B1 subunit (Atp6v1b1)-Cre (B1-Cre) mice. Although Atp6v1b1 is considered kidney specific, it is expressed in multiple organ systems, both in mice and humans, raising the possibility of off-target effects when using the Cre-lox system. We have recently shown using single-cell RNA sequencing that the gene that codes for the V-ATPase G3 subunit (mouse gene: Atp6v1g3; human gene: ATP6V1G3; protein abbreviation: G3) mRNA is selectively enriched in human kidney ICs. In this study, we generated Atp6v1g3-Cre (G3-Cre) reporter mice using CRISPR/CAS technology and crossed them with Tdtomatoflox/flox mice. The resultant G3-Cre+Tdt+ progeny was evaluated for kidney specificity in multiple tissues and found to be highly specific to kidney cells with minimal or no expression in other organs evaluated compared with B1-Cre mice. Tdt+ cells were flow sorted and were enriched for IC marker genes on RT-PCR analysis. Next, we crossed these mice to ihCD59 mice to generate an IC depletion mouse model (G3-Cre+ihCD59+/+). ICs were depleted in these mice using intermedilysin, which resulted in lower blood pH, suggestive of a distal renal tubular acidosis phenotype. The G3-Cre mice were healthy, bred normally, and produce regular-sized litter. Thus, this new "IC reporter" mice can be a useful tool to study ICs.NEW & NOTEWORTHY This study details the development, validation, and experimental use of a new mouse model to study the collecting duct and intercalated cells. Kidney intercalated cells are a cell type increasingly recognized to be important in several human diseases including kidney infections, acid-base disorders, and acute kidney injury.

Bsep/Abcb11 knockout ameliorates Schistosoma mansoni liver pathology by reducing parasite fecundity.

Schistosoma mansoni infection is one of the worldwide leading causes of liver fibrosis and portal hypertension. The objective of this study was to evaluate whether polyhydroxylated bile acids (BAs), known to protect mice from the development of acquired cholestatic liver injury, counteract S. mansoni-induced inflammation and fibrosis. Adult FVB/N wild type (WT) and Abcb11/Bsep-/- mice were infected with either 25 or 50 S. mansoni cercariae. Eight weeks post infection, effects on liver histology, serum biochemistry, gene expression profile of proinflammatory cytokines and fibrotic markers, hepatic hydroxyproline content and FACS analysis were performed. Bsep-/- mice infected with S. mansoni showed significantly less hepatic inflammation and tendentially less fibrosis compared to infected WT mice. Despite elevated alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels in infected Bsep-/- mice, inflammatory cells such as M2 macrophages and Mac-2/galectin-3+ cells were reduced in these animals. Accordingly, mRNA-expression levels of anti-inflammatory cytokines (IL-4 and IL-13) were increased in Bsep-/- mice upon infection. Furthermore, infected Bsep-/- mice exhibited decreased hepatic egg load and parasite fecundity, consequently affecting the worm reproduction rate. This outcome could arise from elevated serum BA levels and lower blood pH in Bsep-/- mice. The loss of Bsep and the resulting changes in bile acid composition and blood pH are associated with the reduction of parasite fecundity, thus attenuating the development of S. mansoni-induced hepatic inflammation and fibrosis.

Multiorgan recovery in a cadaver body using mild hypothermic ECMO treatment in a murine model

BackgroundTransplant candidates on the waiting list are increasingly challenged by the lack of organs. Most of the organs can only be kept viable within very limited timeframes (e.g., mere 4–6 h for heart and lungs exposed to refrigeration temperatures ex vivo). Donation after circulatory death (DCD) using extracorporeal membrane oxygenation (ECMO) can significantly enlarge the donor pool, organ yield per donor, and shelf life. Nevertheless, clinical attempts to recover organs for transplantation after uncontrolled DCD are extremely complex and hardly reproducible. Therefore, as a preliminary strategy to fulfill this task, experimental protocols using feasible animal models are highly warranted. The primary aim of the study was to develop a model of ECMO-based cadaver organ recovery in mice. Our model mimics uncontrolled organ donation after an “out-of-hospital” sudden unexpected death with subsequent “in-hospital” cadaver management post-mortem. The secondary aim was to assess blood gas parameters, cardiac activity as well as overall organ state. The study protocol included post-mortem heparin–streptokinase administration 10 min after confirmed death induced by cervical dislocation under full anesthesia. After cannulation, veno-arterial ECMO (V–A ECMO) was started 1 h after death and continued for 2 h under mild hypothermic conditions followed by organ harvest. Pressure- and flow-controlled oxygenated blood-based reperfusion of a cadaver body was accompanied by blood gas analysis (BGA), electrocardiography, and histological evaluation of ischemia–reperfusion injury. For the first time, we designed and implemented, a not yet reported, miniaturized murine hemodialysis circuit for the treatment of severe hyperkalemia and metabolic acidosis post-mortem.ResultsBGA parameters confirmed profound ischemia typical for cadavers and incompatible with normal physiology, including extremely low blood pH, profound negative base excess, and enormously high levels of lactate. Two hours after ECMO implantation, blood pH values of a cadaver body restored from < 6.5 to 7.3 ± 0.05, pCO2 was lowered from > 130 to 41.7 ± 10.5 mmHg, sO2, base excess, and HCO3 were all elevated from below detection thresholds to 99.5 ± 0.6%, − 4 ± 6.2 and 22.0 ± 6.0 mmol/L, respectively (Student T test, p < 0.05). A substantial decrease in hyperlactatemia (from > 20 to 10.5 ± 1.7 mmol/L) and hyperkalemia (from > 9 to 6.9 ± 1.0 mmol/L) was observed when hemodialysis was implemented. On balance, the first signs of regained heart activity appeared on average 10 min after ECMO initiation without cardioplegia or any inotropic and vasopressor support. This was followed by restoration of myocardial contractility with a heart rate of up to 200 beats per minute (bpm) as detected by an electrocardiogram (ECG). Histological examinations revealed no evidence of heart injury 3 h post-mortem, whereas shock-specific morphological changes relevant to acute death and consequent cardiac/circulatory arrest were observed in the lungs, liver, and kidney of both control and ECMO-treated cadaver mice.ConclusionsThus, our model represents a promising approach to facilitate studying perspectives of cadaveric multiorgan recovery for transplantation. Moreover, it opens new possibilities for cadaver organ treatment to extend and potentiate donation and, hence, contribute to solving the organ shortage dilemma.

Predictors of disease severity and outcomes in pediatric patients with croup and COVID-19 in the pediatric emergency department

BackgroundCroup caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging disease, and data on the risk factors associated with disease severity are still limited.The Westley croup score (WS) is widely used to assess croup severity. The current study aimed to analyze biomarkers associated with the WS and clinical outcomes in patients with croup and coronavirus disease 2019 in the pediatric emergency department (PED). Population and methodPatients diagnosed with croup caused by SARS-CoV-2 were admitted at two PEDs. Clinical data including age, WS, length of hospital stay, initial laboratory data, and treatment were analyzed. Clinical parameters were evaluated via multivariate logistic regression analysis. The best cutoff values for predicting croup severity and outcomes were identified using the receiver operating characteristic curve. ResultIn total, 250 patients were assessed. Moreover, 128 (51.2%) patients were discharged from the PED, and 122 (48.8%) were admitted to the hospital. Mild, moderate, and severe croup accounted for 63.6% (n = 159), 32% (n = 80), and 4.4% (n = 11) of all cases, respectively. A high mean age (years), neutrophil count (%), neutrophil-to-lymphocyte ratio (NLR), ALT (U/L), procalcitonin (ng/mL), and hemoglobin (g/dL) level, and length of hospital stay (days), and a low lymphocyte count (%) and blood pH were associated with croup severity and need for intensive care. Based on the multivariate logistic regression model, the NLR remained independent factors associated with croup severity and prognosis. Further, NLR was significantly correlated with WS. The area under the receiver operating characteristic curve of NLR for predicting a WS of ≥3 was 0.895 (0.842–0.948, p < 0.001), and that for predicting ICU admission was 0.795 (0.711–0.879, p < 0.001). The best cutoff values for a WS of ≥3 and ICU admission were 1.65 and 2.06, respectively. ConclusionNLR is correlated with WS and is a reliable, easy-to-use, and cheap biomarker for the early screening and prognosis of croup severity in the PED. A higher NLR may indicate severe croup and the need for further treatment. And the WS score remains reliable for estimating the severity of croup caused by SARS-CoV-2 and the risk of intensive care.

#5177 COVID-19 IN ELDERLY CHRONIC HEMODIALYSIS PATIENTS: PREDICTORS OF MORTALITY

Abstract Background and Aims Studies have shown that the incidence of severe COVID-19 pneumonia is higher in elderly patients and especially those with comorbidities including chronic kidney disease. The aim of our study was to determine risk factors for mortality in elderly chronic hemodialysis (HD) patients. Method We conducted a cross-sectional, observational, and analytical study, in the dialysis unit of the internal medicine department at Charles Nicolle Hospital over an 11-month period from September 2020 to August 2021. We studied the correlation between mortality and the different epidemiological, clinical and biological data via the SPSS software. Results We included 59 patients, with a mean age of 73 years [65-93] and a gender ratio of 1. All patients had confirmed COVID-19 infection, chronic kidney failure and required regular HD since at least 3 months. One on four patients had a coronary artery disease, 55% were diabetics and 72% had hypertension. From the 19 patients who underwent chest scan, 68% had severe lesions. Emergency HD had to be conducted for 25% of the patients, mainly because of hyperkalemia. At least one ongoing HD session was interrupted for neurologic, hemodynamic or respiratory instability in 26% of the patients. Mortality rate was 58%. Data that were associated with mortality in the univariate study were oxygen needs (p&amp;lt;10-3), COVID-19 infection severity (p=0.007), and interruption of HD session (p&amp;lt;10-3). Low blood pH levels and high pCo2 levels were also correlated to mortality (p=0.032 and p=0.020). Predictors of mortality in multivariate analysis were high oxygen needs (OR=1.368; 95% CI [1.081-1.732]; P = .009), interruption of HD session (OR=1.426; 95% CI [1.070-1.846]; P = .014) and severe form of COVID-19 infection (OR=1.770; 95% CI [1.062-2.980]; P = .029). Conclusion According to these results, high oxygen needs, severity of COVID-19 infection and interruption of HD session represented risk factors of death in elderly patients undergoing chronic hemodialysis. As highlighted in previous studies, mortality rate in COVID-19 seems to be higher among elderly patients. However, diabetes and cardiovascular diseases were not identified as predictors of mortality in this sample of patients.

Blood pH Analysis in Combination with Molecular Medical Tools in Relation to COVID-19 Symptoms.

The global outbreak of SARS-CoV-2/COVID-19 provided the stage to accumulate an enormous biomedical data set and an opportunity as well as a challenge to test new concepts and strategies to combat the pandemic. New research and molecular medical protocols may be deployed in different scientific fields, e.g., glycobiology, nanopharmacology, or nanomedicine. We correlated clinical biomedical data derived from patients in intensive care units with structural biology and biophysical data from NMR and/or CAMM (computer-aided molecular modeling). Consequently, new diagnostic and therapeutic approaches against SARS-CoV-2 were evaluated. Specifically, we tested the suitability of incretin mimetics with one or two pH-sensitive amino acid residues as potential drugs to prevent or cure long-COVID symptoms. Blood pH values in correlation with temperature alterations in patient bodies were of clinical importance. The effects of biophysical parameters such as temperature and pH value variation in relation to physical-chemical membrane properties (e.g., glycosylation state, affinity of certain amino acid sequences to sialic acids as well as other carbohydrate residues and lipid structures) provided helpful hints in identifying a potential Achilles heel against long COVID. In silico CAMM methods and in vitro NMR experiments (including 31P NMR measurements) were applied to analyze the structural behavior of incretin mimetics and SARS-CoV fusion peptides interacting with dodecylphosphocholine (DPC) micelles. These supramolecular complexes were analyzed under physiological conditions by 1H and 31P NMR techniques. We were able to observe characteristic interaction states of incretin mimetics, SARS-CoV fusion peptides and DPC membranes. Novel interaction profiles (indicated, e.g., by 31P NMR signal splitting) were detected. Furthermore, we evaluated GM1 gangliosides and sialic acid-coated silica nanoparticles in complex with DPC micelles in order to create a simple virus host cell membrane model. This is a first step in exploring the structure-function relationship between the SARS-CoV-2 spike protein and incretin mimetics with conserved pH-sensitive histidine residues in their carbohydrate recognition domains as found in galectins. The applied methods were effective in identifying peptide sequences as well as certain carbohydrate moieties with the potential to protect the blood-brain barrier (BBB). These clinically relevant observations on low blood pH values in fatal COVID-19 cases open routes for new therapeutic approaches, especially against long-COVID symptoms.

Loss of Kir5.1 disturbs acid-base homeostasis in Dahl salt-sensitive rats

Renal basolateral inwardly-rectifying potassium (K ir ) channels contribute to the maintenance of the resting membrane potential and potassium homeostasis. Heteromeric K ir 4.1/K ir 5.1 channels are more sensitive to intracellular acidification than homomeric K ir 4.1 channels. Our previous study demonstrated that genetic mutation of Kcnj16 (the gene encodes K ir 5.1) causes chronic metabolic acidosis with lower blood pH and bicarbonate levels in Dalh salt-sensitive (SS) rats. Here, we aim to investigate the underlying mechanisms. We hypothesized that loss of K ir 5.1 disturbs acid-base homeostasis in SS rats by impairing ammoniagenesis in the proximal tubule and HCO3 - reabsorption in the distal convoluted tubule (DCT).12-week-old male SS WT and SS Kcnj16-/- rats were separated into two groups (N=5 per group). At the end of the experiment, kidneys were flushed and processed for blood pH and Western blot analysis.Western blot analysis indicated that knock out of K ir 5.1 causes lower expression of sodium-coupled neutral amino acid transporter 3 (SNAT3), which may indicate defective ammoniagenesis in the proximal tubule. On the other hand, increased expression of NBCe1 and NHE3 suggests enhanced HCO3 - reabsorption and H + excretion. Additionally, the expression of vacuolar ATPase (V-ATPase), which is a proton pump responsible for controlling the intracellular and extracellular pH of cells, remained the same. In the following experiments, we will further investigate the ammoniagensis in the proximal tubule as well as key bicarbonate transporters in DCT and collecting duct. Funding sources: National Institute of Health Grants R35 HL135749 (to AS), Department of Veterans Affairs grant I01 BX004024 (to AS). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Traumatic intestinal ischemic necrosis.

A 71-year-old male patient presented to our emergency department with a 1-day history of abdominal pain after an accidental fall. Laboratory test results were as follows: a white blood cell count of 2.32 × 109/L, blood lactate of 3.0 mmol/L, pH 7.30, calcitonin precursor level of 71.09 ng/ml, and creatinine of 115 umol/L. The abdominal CT revealed: portal vein gas accumulation (PVGA) accompanied by a fluid-air level; pneumatosis cystoides intestinalis (PCI) manifested as multiple gas collections within the wall of the lower small intestine. Based on lowered blood pH and elevated lactate levels, there was a high suspicion of small intestinal ischemic necrosis. Subsequent emergency laparotomy and pathological examination confirmed necrosis of the small intestine.

The preoperative SOFA score and remnant small intestine length are postoperative risk factors for mortality in patients with non-occlusive mesenteric ischemia: a case-control study.

Non-occlusive mesenteric ischemia (NOMI) is a fatal condition with a low survival rate in most cases. The risk factors for perioperative mortality in NOMI cases are unclear. The purpose of this study was to define the risk factors for mortality in patients with NOMI undergoing surgery. Thirty-eight consecutive patients who underwent surgery for NOMI at Teine Keijinkai Hospital between 2012 and 2020 were included in the study. Patient information, including age, sex, physical findings, comorbidities, laboratory data, and computed tomography and surgical findings were retrospectively analyzed. Of the 38 patients, 18 (47%) died before discharge. Significant univariate predictors of mortality were a high Sequential Organ Failure Assessment (SOFA) score, high lactate level, low blood pH, and short intestinal length after surgery. In the multivariate analysis, a high SOFA score (odds ratio 1.33, P=0.036) and short intestine length after surgery (odds ratio 34.7, P=0.003) were identified as independent risk factors for perioperative mortality. The preoperative SOFA score and postoperative residual intestinal length may be predictors of death in NOMI surgical patients, not age and the content of comorbidities.