Browsing by Subject "Acidosis"

Now showing 1 - 6 of 6
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    Acidic microenvironment and bone pain in cancer-colonized bone
    (SpringerNature, 2015-05-06) Yoneda, Toshiyuki; Hiasa, Masahiro; Nagata, Yuki; Okui, Tatsuo; White, Fletcher A.; Department of Medicine, IU School of Medicine
    Solid cancers and hematologic cancers frequently colonize bone and induce skeletal-related complications. Bone pain is one of the most common complications associated with cancer colonization in bone and a major cause of increased morbidity and diminished quality of life, leading to poor survival in cancer patients. Although the mechanisms responsible for cancer-associated bone pain (CABP) are poorly understood, it is likely that complex interactions among cancer cells, bone cells and peripheral nerve cells contribute to the pathophysiology of CABP. Clinical observations that specific inhibitors of osteoclasts reduce CABP indicate a critical role of osteoclasts. Osteoclasts are proton-secreting cells and acidify extracellular bone microenvironment. Cancer cell-colonized bone also releases proton/lactate to avoid intracellular acidification resulting from increased aerobic glycolysis known as the Warburg effect. Thus, extracellular microenvironment of cancer-colonized bone is acidic. Acidosis is algogenic for nociceptive sensory neurons. The bone is densely innervated by the sensory neurons that express acid-sensing nociceptors. Collectively, CABP is evoked by the activation of these nociceptors on the sensory neurons innervating bone by the acidic extracellular microenvironment created by bone-resorbing osteoclasts and bone-colonizing cancer cells. As current treatments do not satisfactorily control CABP and can elicit serious side effects, new therapeutic interventions are needed to manage CABP. Understanding of the cellular and molecular mechanism by which the acidic extracellular microenvironment is created in cancer-colonized bone and by which the expression and function of the acid-sensing nociceptors on the sensory neurons are regulated would facilitate to develop novel therapeutic approaches for the management of CABP.
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    Acute Kidney Injury Interacts With Coma, Acidosis, and Impaired Perfusion to Significantly Increase Risk of Death in Children With Severe Malaria
    (Oxford University Press, 2022) Namazzi, Ruth; Opoka, Robert; Datta, Dibyadyuti; Bangirana, Paul; Batte, Anthony; Berrens, Zachary; Goings, Michael J.; Schwaderer, Andrew L.; Conroy, Andrea L.; John, Chandy C.; Pediatrics, School of Medicine
    Background: Mortality in severe malaria remains high in children treated with intravenous artesunate. Acute kidney injury (AKI) is a common complication of severe malaria, but the interactions between AKI and other complications on the risk of mortality in severe malaria are not well characterized. Methods: Between 2014 and 2017, 600 children aged 6-48 months to 4 years hospitalized with severe malaria were enrolled in a prospective clinical cohort study evaluating clinical predictors of mortality in children with severe malaria. Results: The mean age of children in this cohort was 2.1 years (standard deviation, 0.9 years) and 338 children (56.3%) were male. Mortality was 7.3%, and 52.3% of deaths occurred within 12 hours of admission. Coma, acidosis, impaired perfusion, AKI, elevated blood urea nitrogen (BUN), and hyperkalemia were associated with increased mortality (all P < .001). AKI interacted with each risk factor to increase mortality (P < .001 for interaction). Children with clinical indications for dialysis (14.4% of all children) had an increased risk of death compared with those with no indications for dialysis (odds ratio, 6.56; 95% confidence interval, 3.41-12.59). Conclusions: AKI interacts with coma, acidosis, or impaired perfusion to significantly increase the risk of death in severe malaria. Among children with AKI, those who have hyperkalemia or elevated BUN have a higher risk of death. A better understanding of the causes of these complications of severe malaria, and development and implementation of measures to prevent and treat them, such as dialysis, are needed to reduce mortality in severe malaria.
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    Electrolyte derangements in critically ill children receiving balanced versus unbalanced crystalloid fluid resuscitation
    (Springer Nature, 2022-12-06) Stanski, Natalja L.; Gist, Katja M.; Pickett, Kaci; Brinton, John T.; Sadlowski, Jennifer; Wong, Hector R.; Mourani, Peter; Soranno, Danielle E.; Kendrick, Jessica; Stenson, Erin K.; Pediatrics, School of Medicine
    Background: Adult studies have demonstrated potential harm from resuscitation with 0.9% sodium chloride (0.9%NaCl), resulting in increased utilization of balanced crystalloids like lactated ringers (LR). The sodium and potassium content of LR has resulted in theoretical safety concerns, although limited data exists in pediatrics. We hypothesized that use of LR for resuscitation would not be associated with increased electrolyte derangements compared to 0.9%NaCl. Methods: A prospective, observational cohort study of critically ill children who received ≥ 20 ml/kg of fluid resuscitation and were admitted to two pediatric intensive care units from November 2017 to February 2020. Fluid groups included patients who received > 75% of fluids from 0.9%NaCl, > 75% of fluids from LR, and a mixed group. The primary outcome was incidence of electrolyte derangements (sodium, chloride, potassium) and acidosis. Results: Among 559 patients, 297 (53%) received predominantly 0.9%NaCl, 74 (13%) received predominantly LR, and 188 (34%) received a mixture. Extreme hyperkalemia (potassium ≥ 6 mmol/L) was more common in 0.9%NaCl group (5.8%) compared to LR group (0%), p 0.05. Extreme acidosis (pH > 7.1) was more common in 0.9%NaCl group (11%) compared to LR group (1.6%), p 0.016. Conclusions: LR is associated with fewer electrolyte derangements compared to 0.9%NaCl. Prospective interventional trials are needed to validate these findings.
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    Hyperkalemia and Metabolic Acidosis Occur at a Higher eGFR in Sickle Cell Disease
    (Wolters Kluwer, 2022-02-03) Saraf, Santosh L.; Derebail, Vimal K.; Zhang, Xu; Machado, Roberto F.; Gordeuk, Victor R.; Lash, James P.; Little, Jane; Medicine, School of Medicine
    Background: People with sickle cell disease (SCD) have an elevated estimated glomerular filtration rate (eGFR) compared with the general population, and this may alter the usual creatinine-based eGFR cutoffs for which physiologic evidence of kidney dysfunction is apparent. This study aimed to identify eGFR thresholds for hyperkalemia and metabolic acidosis in patients with SCD. Methods: This was a cross-sectional analysis of 733 patients with severe (hemoglobin SS or Sβ0-thalassemia) SCD genotype, 238 patients with moderate (hemoglobin SC or Sβ+-thalassemia) SCD genotype, and 1333 age- and sex-matched African Americans from the National Health and Nutrition Examination Survey (NHANES). The prevalence rates of hyperkalemia and metabolic acidosis were compared by eGFR category. Cutoffs for hyperkalemia and metabolic acidosis were determined using generalized additive models. Results: Hyperkalemia and metabolic acidosis were more common in those with severe SCD genotype (13% and 21%, respectively) compared with the NHANES (0.3% and 5%, respectively); the prevalence rates in the moderate SCD genotype were intermediate for hyperkalemia (3%) and metabolic acidosis (11%). The proportion of patients with hyperkalemia and metabolic acidosis progressively increased with lower eGFR category in both SCD genotype groups. The eGFR thresholds for hyperkalemia and metabolic acidosis were higher in the severe (85 and 91 ml/min per 1.73 m2, respectively) and moderate (52 and 102 ml/min per 1.73 m2, respectively) SCD genotypes compared with the NHANES (34 and 46 ml/min per 1.73 m2). Conclusions: We demonstrate that hyperkalemia and metabolic acidosis are more common and occur at higher eGFR values in patients with SCD compared with age- and sex-matched African Americans, including in eGFR ranges considered to be normal. Future studies using redefined creatinine-based eGFR thresholds for abnormal kidney function may identify high-risk patients for earlier intervention strategies and referral for specialized renal care in SCD.
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    Intestinal Injury Biomarkers Predict Mortality in Pediatric Severe Malaria
    (American Society for Microbiology, 2022) Sarangam, Maithri L.; Namazzi, Ruth; Datta, Dibyadyuti; Bond, Caitlin; Vanderpool, Charles P.B.; Opoka, Robert O.; John, Chandy C.; Conroy, Andrea L.; Pediatrics, School of Medicine
    Severe malaria (SM) increases the risk of invasive bacterial infection, and there is evidence to suggest increased gastrointestinal permeability. Studies have shown sequestration of infected erythrocytes in intestinal microvasculature, and in vivo studies of rectal mucosa have demonstrated disruption of microvascular blood flow. However, the extent of intestinal injury in pediatric malaria is not well characterized. In this study, two serum biomarkers of intestinal injury, trefoil factor 3 (TFF3) and intestinal fatty acid binding protein (I-FABP), were analyzed in 598 children with SM and 120 healthy community children (CC), 6 months to 4 years of age. Serum was collected at enrollment and 1 month for laboratory studies, and participants were monitored for 12 months. Intestinal injury biomarkers were significantly elevated in children with SM, with 18.1% having levels of TFF3 and/or I-FABP greater than the 99th percentile of CC levels. TFF3 levels continued to be elevated at 1 month, while I-FABP levels were comparable to CC levels. Both markers predicted in-hospital mortality {odds ratio (OR) (95% confidence interval [CI]), 4.4 (2.7, 7.3) and 2.3 (1.7, 3.1)} for a natural log increase in TFF3 and I-FABP, respectively. TFF3 was also associated with postdischarge mortality (OR, 2.43 [95% CI, 1.1, 4.8]). Intestinal injury was associated with acute kidney injury (AKI), acidosis (P < 0.001 for both), and angiopoietin 2, a maker of endothelial activation. In conclusion, intestinal injury is common in pediatric severe malaria and is associated with an increased mortality. It is strongly associated with AKI, acidosis, and endothelial activation. IMPORTANCE: In children with severe malaria, intestinal injury is a common complication associated with increased mortality. Intestinal injury is associated with acute kidney injury, acidosis, and endothelial activation. Interventions promoting intestinal regeneration and repair represent novel approaches to improve outcomes.
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    Maternal Oxygen Supplementation Compared With Room Air for Intrauterine Resuscitation: A Systematic Review and Meta-analysis
    (American Medical Association, 2021) Raghuraman, Nandini; Temming, Lorene A.; Doering, Michelle M.; Stoll, Carolyn R.; Palanisamy, Arvind; Stout, Molly J.; Colditz, Graham A.; Cahill, Alison G.; Tuuli, Methodius G.; Obstetrics and Gynecology, School of Medicine
    Importance: Supplemental oxygen is commonly administered to pregnant women at the time of delivery to prevent fetal hypoxia and acidemia. There is mixed evidence on the utility of this practice. Objective: To compare the association of peripartum maternal oxygen administration with room air on umbilical artery (UA) gas measures and neonatal outcomes. Data sources: Ovid MEDLINE, Embase, Scopus, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials were searched from February 18 to April 3, 2020. Search terms included labor or obstetric delivery and oxygen therapy and fetal blood or blood gas or acid-base imbalance. Study selection: Studies were included if they were randomized clinical trials comparing oxygen with room air at the time of scheduled cesarean delivery or labor in patients with singleton, nonanomalous pregnancies. Studies that did not collect paired umbilical cord gas samples or did not report either UA pH or UA Pao2 results were excluded. Data extraction and synthesis: Data were extracted by 2 independent reviewers. The analysis was stratified by the presence or absence of labor at the time of randomization. Data were pooled using random-effects models. Main outcomes and measures: The primary outcome for this review was UA pH. Secondary outcomes included UA pH less than 7.2, UA Pao2, UA base excess, 1- and 5-minute Apgar scores, and neonatal intensive care unit admission. Results: The meta-analysis included 16 randomized clinical trials (n = 1078 oxygen group and n = 974 room air group). There was significant heterogeneity among the studies (I2 = 49.88%; P = .03). Overall, oxygen administration was associated with no significant difference in UA pH (weighted mean difference, 0.00; 95% CI, -0.01 to 0.01). Oxygen use was associated with an increase in UA Pao2 (weighted mean difference, 2.57 mm Hg; 95% CI, 0.80-4.34 mm Hg) but no significant difference in UA base excess, UA pH less than 7.2, Apgar scores, or neonatal intensive care unit admissions. Umbilical artery pH values remained similar between groups after accounting for the risk of bias, type of oxygen delivery device, and fraction of inspired oxygen. After stratifying by the presence or absence of labor, oxygen administration in women undergoing scheduled cesarean delivery was associated with increased UA Pao2 (weighted mean difference, 2.12 mm Hg; 95% CI, 0.09-4.15 mm Hg) and a reduction in the incidence of UA pH less than 7.2 (relative risk, 0.63; 95% CI, 0.43-0.90), but these changes were not noted among those in labor (Pao2: weighted mean difference, 3.60 mm Hg; 95% CI, -0.30 to 7.49 mm Hg; UA pH<7.2: relative risk, 1.34; 95% CI, 0.58-3.11). Conclusions and relevance: This systematic review and meta-analysis suggests that studies to date showed no association between maternal oxygen and a clinically relevant improvement in UA pH or other neonatal outcomes.