Patrick Lahni
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View article: Development of population pharmacokinetic models of total and free piperacillin in critically ill children and young adults for Monte Carlo simulations and model-informed precision dosing
Development of population pharmacokinetic models of total and free piperacillin in critically ill children and young adults for Monte Carlo simulations and model-informed precision dosing Open
Objectives We sought to develop population pharmacokinetic (PopPK) models of total and free piperacillin in critically ill children and young adults. We investigated the impact of kidney function and injury biomarkers and the effect of tim…
View article: Inflammatory and tissue injury marker dynamics in pediatric acute respiratory distress syndrome
Inflammatory and tissue injury marker dynamics in pediatric acute respiratory distress syndrome Open
BACKGROUNDThe molecular signature of pediatric acute respiratory distress syndrome (ARDS) is poorly described, and the degree to which hyperinflammation or specific tissue injury contributes to outcomes is unknown. Therefore, we profiled i…
View article: Obesity Alters cytokine signaling and gut microbiome in septic mice
Obesity Alters cytokine signaling and gut microbiome in septic mice Open
Sepsis is a leading cause of mortality. Plasma cytokine levels may identify those at increased risk of mortality from sepsis. Our aim was to understand how obesity alters cytokine levels during early sepsis and its correlation with surviva…
View article: Comparison of 16 Pediatric Acute Respiratory Distress Syndrome-Associated Plasma Biomarkers With Changing Lung Injury Severity*
Comparison of 16 Pediatric Acute Respiratory Distress Syndrome-Associated Plasma Biomarkers With Changing Lung Injury Severity* Open
OBJECTIVES: Pediatric acute respiratory distress syndrome (PARDS) is a source of substantial morbidity and mortality in the PICU, and different plasma biomarkers have identified different PARDS and ARDS subgroups. We have a poor understand…
View article: Detrimental effects of PCSK9 loss-of-function in the pediatric host response to sepsis are mediated through independent influence on Angiopoietin-1
Detrimental effects of PCSK9 loss-of-function in the pediatric host response to sepsis are mediated through independent influence on Angiopoietin-1 Open
Background Sepsis is associated with significant mortality. Yet, there are no efficacious therapies beyond antibiotics. PCSK9 loss-of-function (LOF) and inhibition, through enhanced low-density lipoprotein receptor (LDLR) mediated endotoxi…
View article: Biomarker-Based Risk Stratification in Pediatric Sepsis From a Low-Middle Income Country*
Biomarker-Based Risk Stratification in Pediatric Sepsis From a Low-Middle Income Country* Open
Objectives: Most biomarker studies of sepsis originate from high-income countries, whereas mortality risk is higher in low- and middle-income countries. The second version of the Pediatric Sepsis Biomarker Risk Model (PERSEVERE-II) has bee…
View article: PROTECTIVE EFFECTS OF HUMANIN-G IN HEMORRHAGIC SHOCK IN FEMALE MICE VIA AMPKα1-INDEPENDENT MECHANISMS
PROTECTIVE EFFECTS OF HUMANIN-G IN HEMORRHAGIC SHOCK IN FEMALE MICE VIA AMPKα1-INDEPENDENT MECHANISMS Open
Introduction: Despite therapeutic advances in hemorrhagic shock, mortality from multiple organ failure remains high. We previously showed that the α1 subunit of AMP-activated protein kinase (AMPK), a crucial regulator of mitochondrial func…
View article: SEX-DEPENDENT EFFECTS OF ADIPOCYTE STAT3 INHIBITION ON THE INFLAMMATORY RESPONSE DURING SEVERE SEPSIS
SEX-DEPENDENT EFFECTS OF ADIPOCYTE STAT3 INHIBITION ON THE INFLAMMATORY RESPONSE DURING SEVERE SEPSIS Open
Introduction: Sepsis is a dysregulated host response to infection that can lead to life-threatening organ dysfunction. Clinical and animal studies consistently demonstrate that female subjects are less susceptible to the adverse effects of…
View article: Detrimental effects of PCSK9 loss-of-function in the pediatric host response to sepsis are mediated through independent influence on Angiopoietin-1
Detrimental effects of PCSK9 loss-of-function in the pediatric host response to sepsis are mediated through independent influence on Angiopoietin-1 Open
Background: Sepsis is associated with significant mortality, yet there are no efficacious therapies beyond antibiotics and supportive care. In adult sepsis studies, PCSK9 loss-of-function (LOF) and inhibition has shown therapeutic promise,…
View article: Colivelin, a synthetic derivative of humanin, ameliorates endothelial injury and glycocalyx shedding after sepsis in mice
Colivelin, a synthetic derivative of humanin, ameliorates endothelial injury and glycocalyx shedding after sepsis in mice Open
Endothelial dysfunction plays a central role in the pathogenesis of sepsis-mediated multiple organ failure. Several clinical and experimental studies have suggested that the glycocalyx is an early target of endothelial injury during an inf…
View article: Choline supplementation attenuates experimental sepsis-associated acute kidney injury
Choline supplementation attenuates experimental sepsis-associated acute kidney injury Open
Altered choline metabolism plays a role in both human and murine sepsis-associated acute kidney injury (SA-AKI), and choline administration in experimental SA-AKI improved renal function. These findings indicate that 1) mouse models can he…
View article: Multi-omic Characterization of Pediatric ARDS via Nasal Brushings
Multi-omic Characterization of Pediatric ARDS via Nasal Brushings Open
RationaleWhile nasal brushing transcriptomics can identify disease subtypes in chronic pulmonary diseases, it is unknown whether this is true in pediatric ARDS (PARDS).ObjectivesDetermine whether nasal transcriptomics and methylomics can i…
View article: Matrix metalloproteinases and their inhibitors in pediatric severe acute pancreatitis
Matrix metalloproteinases and their inhibitors in pediatric severe acute pancreatitis Open
Background Acute pancreatitis (AP) is increasing in incidence in adult and pediatric patients. Identification of patients at high risk for progression to severe acute pancreatitis (SAP) is crucial, as it can lead to increased mortality and…
View article: Obesity protects against sepsis-induced and norepinephrine-induced white adipose tissue browning
Obesity protects against sepsis-induced and norepinephrine-induced white adipose tissue browning Open
White adipose tissue browning is detrimental in patients with burn injury and cancer. WAT browning occurs in nonobese mice and can be induced by β receptor norepinephrine infusion, but obese mice are resistant to sepsis-induced and norepin…
View article: NMR-based serum and urine metabolomic profile reveals suppression of mitochondrial pathways in experimental sepsis-associated acute kidney injury
NMR-based serum and urine metabolomic profile reveals suppression of mitochondrial pathways in experimental sepsis-associated acute kidney injury Open
NMR-based metabolomics revealed disruptions in branched-chain amino acid metabolism, fatty acid oxidation, and NAD + synthesis in sepsis-associated acute kidney injury. These pathways represent essential processes for energy provision in r…
View article: Olfactomedin 4–Positive Neutrophils Are Upregulated after Hemorrhagic Shock
Olfactomedin 4–Positive Neutrophils Are Upregulated after Hemorrhagic Shock Open
Neutrophils are vital to both the inflammatory cascade and tissue repair after an injury. Neutrophil heterogeneity is well established but there is less evidence for significant, different functional roles for neutrophil subsets. OLFM4 (Ol…
View article: Hepatocyte-Specific Deletion of AMPKα1 Results in Worse Outcomes in Mice Subjected to Sepsis in a Sex-Specific Manner
Hepatocyte-Specific Deletion of AMPKα1 Results in Worse Outcomes in Mice Subjected to Sepsis in a Sex-Specific Manner Open
Alterations in the energy homeostasis contribute to sepsis-mediated multiple organ failure. The liver plays a central role in metabolism and participates to the innate immune and inflammatory responses of sepsis. Several clinical and exper…
View article: Olfactomedin 4 marks a subset of neutrophils in mice
Olfactomedin 4 marks a subset of neutrophils in mice Open
Neutrophils are the most abundant immune cell of the innate immune system and participate in essential immune functions. Heterogeneity within neutrophils has been documented, but it is difficult to distinguish if these are altered activati…
View article: Interleukin-27 as a candidate diagnostic biomarker for bacterial infection in immunocompromised pediatric patients
Interleukin-27 as a candidate diagnostic biomarker for bacterial infection in immunocompromised pediatric patients Open
Despite prior work demonstrating IL-27 and PCT as possible biomarkers of bacterial infection in immunocompromised pediatric patients, we were unable to validate these findings. This illustrates the challenges associated with developing rel…
View article: Age-dependent cardiac function during experimental sepsis: effect of pharmacological activation of AMP-activated protein kinase by AICAR
Age-dependent cardiac function during experimental sepsis: effect of pharmacological activation of AMP-activated protein kinase by AICAR Open
Age represents a major risk factor for multiple organ failure, including cardiac dysfunction, in patients with sepsis. AMP-activated protein kinase (AMPK) is a crucial regulator of energy homeostasis that controls mitochondrial biogenesis …
View article: Autophagy and mitochondrial biogenesis impairment contribute to age‐dependent liver injury in experimental sepsis: dysregulation of AMP‐activated protein kinase pathway
Autophagy and mitochondrial biogenesis impairment contribute to age‐dependent liver injury in experimental sepsis: dysregulation of AMP‐activated protein kinase pathway Open
Age is an independent risk factor of multiple organ failure in patients with sepsis. However, the age‐related mechanisms of injury are not known. AMPK is a crucial regulator of energy homeostasis, which controls mitochondrial biogenesis by…
View article: Metformin Exerts Beneficial Effects in Hemorrhagic Shock in An AMPKα1-Independent Manner
Metformin Exerts Beneficial Effects in Hemorrhagic Shock in An AMPKα1-Independent Manner Open
Despite therapeutic advances in hemorrhagic shock, mortality from multiple organ failure remains high. AMP-activated protein kinase (AMPK) is involved in cellular energy homeostasis. Two catalytic subunits, α1 and α2, have been identified,…
View article: Zinc supplementation leads to immune modulation and improved survival in a juvenile model of murine sepsis
Zinc supplementation leads to immune modulation and improved survival in a juvenile model of murine sepsis Open
Children with severe sepsis are known to have altered zinc homeostasis and decreased circulating zinc levels, suggesting a role for zinc supplementation to improve outcomes. We tested the hypothesis that zinc supplementation would improve …
View article: Olfactomedin-4 Is a Candidate Marker for a Pathogenic Neutrophil Subset in Septic Shock
Olfactomedin-4 Is a Candidate Marker for a Pathogenic Neutrophil Subset in Septic Shock Open
Objectives: Heterogeneity in sepsis-related pathobiology presents a significant challenge. Resolving this heterogeneity presents an opportunity to understand pathobiology and improve patient care. Olfactomedin-4 is a neutrophil subset mark…