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Cureus May 2024A rare complication, 5-oxoproline-induced high anion gap metabolic acidosis (HAGMA) is associated with chronic acetaminophen use, predominantly reported in outpatient...
A rare complication, 5-oxoproline-induced high anion gap metabolic acidosis (HAGMA) is associated with chronic acetaminophen use, predominantly reported in outpatient settings. However, its occurrence in hospitalized patients, particularly those with end-stage renal disease (ESRD), remains underreported. We present a case of a 74-year-old female with ESRD on hemodialysis who developed HAGMA highly suspicious for 5-oxoproline toxicity from acetaminophen usage following cardiac surgery. Despite a standard analgesic dose, the patient's renal impairment likely predisposed her to 5-oxoproline accumulation, resulting in severe metabolic acidosis. Discontinuation of acetaminophen led to the resolution of HAGMA, highlighting the importance of recognizing this rare but potentially life-threatening complication in the inpatient and critical care setting. This case suggests a potential interaction between acetaminophen metabolism and renal dysfunction in the pathogenesis of 5-oxoproline-induced HAGMA.
PubMed: 38947688
DOI: 10.7759/cureus.61328 -
JCEM Case Reports Jul 2024Diazoxide is a commonly used first-line medication for the treatment of hyperinsulinism. Hyperglycemia may occur with diazoxide use. However, hyperglycemic hyperosmolar...
Diazoxide is a commonly used first-line medication for the treatment of hyperinsulinism. Hyperglycemia may occur with diazoxide use. However, hyperglycemic hyperosmolar state (HHS) secondary to diazoxide is an exceedingly rare but potentially life-threatening adverse effect. We present a case of a 2-year-old with Kabuki syndrome and hyperinsulinism on diazoxide. She presented with 4 days of fever, respiratory symptoms, and lethargy. She was influenza B positive. Initial workup indicated HHS, with an elevated serum glucose (47.1 mmol/L [847.8 mg/dL]; reference range 3.9-6.0 mmol/L; 70-108 mg/dL), serum osmolality (357 mmol/kg HO; reference 282-300 mmol/kg HO) but absent urine ketones and no metabolic acidosis (venous pH 7.34). Her course was complicated by an acute kidney injury. Management in the hospital included discontinuation of diazoxide and intravenous fluid resuscitation, following which hyperglycemia and hyperosmolarity resolved. No insulin therapy was required. She remained normoglycemic without diazoxide for 2 weeks but subsequently required restarting of diazoxide for hypoglycemia. This case highlights the need for early recognition and prompt management of diazoxide-related HHS to reduce negative outcomes. We present the first case report of a child with Kabuki syndrome and hyperinsulinism with diazoxide-induced HHS.
PubMed: 38947417
DOI: 10.1210/jcemcr/luae108 -
AJOG Global Reports Aug 2024Intrahepatic cholestasis of pregnancy has been linked to sudden stillbirth. The suddenness of the stillbirths in these cases have led clinicians to suspect that the...
BACKGROUND
Intrahepatic cholestasis of pregnancy has been linked to sudden stillbirth. The suddenness of the stillbirths in these cases have led clinicians to suspect that the pathogenesis of stillbirth in women with intrahepatic cholestasis of pregnancy is not related to asphyxia but rather to an undefined etiology. One leading hypothesis relates certain bile acid metabolites to myocardial injury.
OBJECTIVE
The purpose of this study was to determine whether cord blood troponin I levels are increased in fetuses born to mothers with a diagnosis of intrahepatic cholestasis of pregnancy.
STUDY DESIGN
A prospective, case-control study was performed at a single institution between 2017 to 2019 in which 87 pregnant patients with a diagnosis of intrahepatic cholestasis of pregnancy (total bile acids ≥10 μmol/L) were enrolled as cases and 122 randomly selected pregnant patients (asymptomatic with intrapartum total bile acids <10 μmol/L) were enrolled as controls. Cord blood troponin I levels were measured at delivery in both groups using a commercially available chemiluminescent immunoassay. Values ≤0.04 ng/mL were considered negative. Values >0.04 ng/mL were considered positive. The primary outcome was the presence of elevated troponin levels in both cases and controls as a surrogate marker for cardiac status. Our secondary outcomes included neonatal intensive care unit stay, low Apgar scores, neonatal acidosis, and hypoxia indicated by cord blood pH and base excess levels at the time of birth. Chi square and tests were performed to compare social and obstetrical variables. A value of <.05 was considered significant. A stratification by total bile acids range of <40 μmol/L, 40 to 100 μmol/L, and >100 μmol/L was performed to assess the relationship between the different severities of intrahepatic cholestasis of pregnancy (by risk of fetal demise with those with total bile acids of >100 μmol/L considered at greatest risk) and the likelihood of a positive troponin I result. Finally, a logistic regression analysis was performed to determine if levels of ≥10 μmol/L were associated with elevated troponin levels.
RESULTS
The mean gestational age at delivery was 38.96±1.47 and 37.71±1.59 weeks of gestation in the controls and cases respectively (<.001). The mean total bile acids values were 5.2±1.28 ng/mL and 43.2±40.62 ng/mL in the controls and cases respectively (<.001). Cord blood troponin I was positive in 15 of 122 (12.30%) controls and in 20 of 87 (22.99%) cases. (<.001). When further stratified by total bile acids levels of <40, 40 to 100, and >100 μmol/L, we found a positive correlation between higher total bile acids levels and a positive troponin I test (=.002). When controlling for gestational age at delivery, maternal age, and body mass index, higher total bile acids levels were associated with a positive troponin I level (adjusted odds ratio, 1.015; 95% confidence interval, 1.004-1.026).
CONCLUSION
Elevated troponin I was more likely to be found in patients with intrahepatic cholestasis of pregnancy than in those without intrahepatic cholestasis of pregnancy. When stratified by total bile acids levels, a positive troponin I level was more likely to be found with higher levels of total bile acids. In addition, as total bile acids levels increased, they were more likely to be associated with a positive troponin I level. Although there were no stillbirths in our cohort, our findings suggest a potential relationship between cardiac injury and high levels of total bile acids demonstrated by the presence of elevated troponin I levels in cord blood at the time of birth.
PubMed: 38946940
DOI: 10.1016/j.xagr.2024.100356 -
Journal of Liposome Research Jul 2024Emtricitabine (FTC) a BCS class I drug, is used for HIV prevention. The high solubility of the drug is the leading cause of severe hepatotoxicity and lactic acidosis....
Emtricitabine (FTC) a BCS class I drug, is used for HIV prevention. The high solubility of the drug is the leading cause of severe hepatotoxicity and lactic acidosis. This research focuses on the use of modified pullulan for the preparation of polymeric liposomes of FTC. Modified pullulan was synthesized using cholesterol, and succinic anhydride in a controlled chemical environment. The formation of the polymer was established through analysis of spectra. Varying the drug-polymer ratio (1:1, 1:2, and 1:3), the drug-polymer composite was loaded in the vesicular system of soya phosphatidylcholine and cholesterol. Formulations were evaluated for drug entrapment, particle size, surface morphology, and and drug release. An study of the pure drug and the best formulation on mice was conducted for 28 days following daily oral administration to evaluate the effect on liver and hematological parameters. The best formulation was further subjected to cytotoxicity study on hepatic cell lines. Spectral analysis confirmed the formation of modified pullulan. All formulations showed high drug entrapment in the nanovesicles. and drug release profiles depicted a controlled release of the drug. Hematological parameters were found to be under control in the animals throughout the experimentation. A comparative histopathology study on the livers and cytotoxicity study on hepatic cell lines revealed the safety of the best formulation over the pure drug. Hence it can be concluded that polymeric liposomes of FTC can be a promising mode of delivery to overcome its limitations.
PubMed: 38946524
DOI: 10.1080/08982104.2024.2362352 -
American Journal of Critical Care : An... Jul 2024Death after resuscitation from cardiac arrest is common. Although associated factors have been identified, knowledge about their relationship with specific modes of...
BACKGROUND
Death after resuscitation from cardiac arrest is common. Although associated factors have been identified, knowledge about their relationship with specific modes of death is limited.
OBJECTIVE
To identify clinical factors associated with specific modes of death following cardiac arrest.
METHODS
This study involved a retrospective medical record review of patients admitted to a single health care center from January 2015 to March 2020 after resuscitation from cardiac arrest who died during their index hospitalization. Mode of death was categorized as either brain death, withdrawal of life-sustaining therapies due to neurologic causes, death due to medical causes, or withdrawal of life-sustaining therapies due to patient preference. Clinical characteristics across modes of death were compared.
RESULTS
The analysis included 731 patients. Death due to medical causes was the most common mode of death. Compared with the other groups of patients, those with brain death were younger, had fewer comorbidities, were more likely to have experienced unwitnessed and longer cardiac arrest, and had more severe acidosis and hyperglycemia on presentation. Patients who died owing to medical causes or withdrawal of life-sustaining therapies due to patient preference were older and had more comorbidities, fewer unfavorable cardiac arrest characteristics, and fewer days between cardiac arrest and death.
CONCLUSIONS
Significant associations were found between several clinical characteristics and specific mode of death following cardiac arrest. Decision-making regarding withdrawal of care after resuscitation from cardiac arrest should be based on a multimodal approach that takes account of a variety of personal and clinical factors.
Topics: Humans; Male; Female; Retrospective Studies; Aged; Middle Aged; Heart Arrest; Cause of Death; Withholding Treatment; Cardiopulmonary Resuscitation; Brain Death; Aged, 80 and over; Age Factors; Comorbidity; Patient Preference
PubMed: 38945819
DOI: 10.4037/ajcc2024145 -
Microcirculation (New York, N.Y. : 1994) Jun 2024This study focuses on evaluating the disruptions in key physiological parameters during microstroke events to assess their severity.
OBJECTIVE
This study focuses on evaluating the disruptions in key physiological parameters during microstroke events to assess their severity.
METHODS
A mathematical model was developed to simulate the changes in cerebral tissue pO, glucose concentration, and temperature due to blood flow interruptions. The model considers variations in baseline cerebral blood flow (CBF), capillary density, and blood oxygen/glucose levels, as well as ambient temperature changes.
RESULTS
Simulations indicate that complete blood flow obstruction still allows for limited glucose availability, supporting nonoxidative metabolism and potentially exacerbating lactate buildup and acidosis. Partial obstructions decrease tissue pO, with minimal impact on glucose level, which can remain almost unchanged or even slightly increase. Reduced CBF, capillary density, or blood oxygen due to aging or disease enhances hypoxia risk at lower obstruction levels, with capillary density having a significant effect on stroke severity by influencing both pO and glucose levels. Conditions could lead to co-occurrence of hypoxia/hypoglycemia or hypoxia/hyperglycemia, each worsening outcomes. Temperature effects were minimal in deep brain regions but varied near the skull by 0.2-0.8°C depending on ambient temperature.
CONCLUSIONS
The model provides insights into the conditions driving severe stroke outcomes based on estimated levels of hypoxia, hypoglycemia, hyperglycemia, and temperature changes.
PubMed: 38944839
DOI: 10.1111/micc.12872 -
Cell Reports Jun 2024Harsh environments in poorly perfused tumor regions may select for traits driving cancer aggressiveness. Here, we investigated whether tumor acidosis interacts with...
Harsh environments in poorly perfused tumor regions may select for traits driving cancer aggressiveness. Here, we investigated whether tumor acidosis interacts with driver mutations to exacerbate cancer hallmarks. We adapted mouse organoids from normal pancreatic duct (mN10) and early pancreatic cancer (mP4, KRAS-G12D mutation, ± p53 knockout) from extracellular pH 7.4 to 6.7, representing acidic niches. Viability was increased by acid adaptation, a pattern most apparent in wild-type (WT) p53 organoids, and exacerbated upon return to pH 7.4. This led to increased survival of acid-adapted organoids treated with gemcitabine and/or erlotinib, and, in WT p53 organoids, acid-induced attenuation of drug effects. New genetic variants became dominant during adaptation, yet they were unlikely to be its main drivers. Transcriptional changes induced by acid and drug adaptation differed overall, but acid adaptation increased the expression of gemcitabine resistance genes. Thus, adaptation to acidosis increases cancer cell viability after chemotherapy.
PubMed: 38944837
DOI: 10.1016/j.celrep.2024.114409 -
STAR Protocols Jun 2024Tumor acidosis is one of the hallmarks indicating the initiation and progression of various cancers. Here, we present a protocol for preparing a hyperpolarized (HP)...
Tumor acidosis is one of the hallmarks indicating the initiation and progression of various cancers. Here, we present a protocol for preparing a hyperpolarized (HP) C-bicarbonate tissue pH MRI imaging contrast agent to detect aggressive tumors. We describe the steps for the formulation and polarization of a precursor molecule C-glycerol carbonate (C-GLC), the post-dissolution reaction, and converting HP C-GLC to an injectable HP C-bicarbonate solution. We then detail procedures for MRI data acquisition to generate tumor pH maps for assessing tumor aggressiveness. For complete details on the use and execution of this protocol, please refer to Mu et al..
PubMed: 38943645
DOI: 10.1016/j.xpro.2024.103091 -
Veterinary Journal (London, England :... Jun 2024We determined the association between urine pH and blood acid-base indicators and assessed a urine pH cut-off value to predict severe metabolic acidosis under field...
We determined the association between urine pH and blood acid-base indicators and assessed a urine pH cut-off value to predict severe metabolic acidosis under field conditions in cows fed acidogenic diets. Eighty-six cows were sampled for urine and blood. Urine pH was evaluated immediately after collection and blood acid-base status was evaluated within 2hours of collection using a portable blood analyzer. Twenty-five cows were classified as having severe metabolic acidosis (blood pH 7.4; bicarbonate < 24mmol/L, base excess ≤ -0.5; PCO low to normal concentrations and urine pH between 4.88 and 5.71. There was a positive linear association between urine pH and blood pH (r = 0.46), and between urine pH and base excess (r = 0.74). The area under the ROC curve was 0.91 (CI 95%= 0.84-0.96; good-excellent test). The optimal cut-off value for urine pH to categorize a cow with severe metabolic acidosis was 5.5 (94% specificity and 72% sensitivity). For each 0.1 unit of decrease in urine pH below 5.5, cows were 1.6 times (95% CI= 1.3- 2.1) more likely to exhibit a severe metabolic acidosis. We conclude that a urine pH of 5.5 or less is indicative of more life-threatening metabolic acidosis in dairy cows.
PubMed: 38942283
DOI: 10.1016/j.tvjl.2024.106187 -
Cureus May 2024Acute lymphoblastic leukemia (ALL) is the most prevalent pediatric malignancy, accounting for approximately 25% of childhood cancers. Despite significant advancements in...
Acute lymphoblastic leukemia (ALL) is the most prevalent pediatric malignancy, accounting for approximately 25% of childhood cancers. Despite significant advancements in treatment protocols, ALL remains a complex disease, often presenting with various complications, including the rare metabolic disturbance of type B lactic acidosis. This case report details the clinical journey of a 14-year-old female with ALL who developed type B lactic acidosis during treatment. The patient presented with intermittent fever, abdominal pain, jaundice, and hepatosplenomegaly, accompanied by severe anemia and thrombocytopenia. Initial management included supportive care and chemotherapy initiation. Despite aggressive interventions, the patient's condition deteriorated, with escalating lactic acidosis and respiratory distress, leading to a critical need for tailored management strategies. This report underscores the importance of early recognition and comprehensive management of type B lactic acidosis in pediatric ALL, highlighting its multifactorial etiology and potentially life-threatening consequences. Enhanced clinical awareness and a multidisciplinary approach are crucial for improving outcomes in such complex cases.
PubMed: 38939285
DOI: 10.7759/cureus.61201