bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early fluid plus norepinephrine resuscitation diminishes kidney hypoperfusion and inflammation in septic newborn pigs
Authors: Fanous Mina S. , de la Cruz Julia E. , Michael Olugbenga S. , Afolabi Jeremiah M. , Kumar Ravi , Adebiyi Adebowale 
Published: April 2024

AbstractSepsis is the most frequent risk factor for acute kidney injury (AKI) in critically ill infants. Sepsis-induced dysregulation of kidney microcirculation in newborns is unresolved. The objective of this study was to use the translational swine model to evaluate changes in kidney function during the early phase of sepsis in newborns and the impact of fluid plus norepinephrine (NE) resuscitation. Newborn pigs (3-7-day-old) were allocated randomly to three groups: 1) Sham, 2) Sepsis (cecal ligation and puncture; CLP) without subsequent resuscitation, and 3) Sepsis with Lactated Ringer plus NE resuscitation. All animals underwent standard anesthesia and mechanical ventilation. Cardiac output (COP) and glomerular filtration rate (GFR) were measured non-invasively. Mean arterial pressure (MAP), total renal blood flow (RBF), cortical perfusion (coPf), medullary perfusion (mePf), and medullary tissue oxygen tension (mtPO2) were determined for 12 h. CLP decreased MAP and COP by more than 50%, with a proportional increase in renal vascular resistance (RVR) and a 60-80% reduction in RBF, coPf, mePf, and mtPO2compared to sham. CLP also decreased GFR by ~79% and increased AKI biomarkers. Isolated foci of tubular necrosis were observed in the septic piglets. Except for mtPO2, changes in all these parameters were ameliorated in resuscitated piglets. Resuscitation also attenuated sepsis-induced increases in the levels of plasma C-reactive protein, proinflammatory cytokines, lactate dehydrogenase, alanine transaminase, aspartate aminotransferase, and renal NLRP3 inflammasome. These data suggest that newborn pigs subjected to CLP develop hypodynamic septic AKI. Early implementation of resuscitation lessens the degree of inflammation, AKI, and liver injury.
Interplay between brain oxygenation and the development of hypothermia in endotoxic shock
Authors: Moretti Eduardo H. , Lino Caroline A. , Steiner Alexandre A. 
Published: April 2024

ABSTRACT
There is evidence to suggest that the hypothermia observed in the most severe cases of systemic inflammation or sepsis is a regulated response with potential adaptive value, but the mechanisms involved are poorly understood. Here, we investigated the interplay between brain oxygenation (assessed by tissue PO2) and the development of hypothermia in unanesthetized rats challenged with a hypotension-inducing dose of bacterial lipopolysaccharide (LPS, 1 mg/kg i.v.). At an ambient temperature of 22 °C, oxygen consumption (V̇O2) began to fall only a few minutes after the LPS injection, and this suppression in metabolic rate preceded the decrease in core temperature. No reduction in brain PO2 was observed prior to the development of the hypometabolic, hypothermic response, ruling out the possibility that brain hypoxia served as a trigger for hypothermia in this model. Brain PO2 was even increased. Such an improvement in brain oxygenation could reflect either an increased O2 delivery or a decreased O2 consumption. The former explanation seems unlikely because blood flow (cardiac output) was being progressively decreased during the recording period. On the other hand, the decrease in V̇O2 usually preceded the rise in PO2, and an inverse correlation between V̇O2 and brain PO2 was consistently observed. These findings do not support the existence of a closed-loop feedback relationship between brain oxygenation and hypothermia in systemic inflammation. The data are consistent with a feedforward mechanism in which hypothermia is triggered (possibly by cryogenic inflammatory mediators) in anticipation of changes in brain oxygenation to prevent the development of tissue hypoxia.
Herpes simplex virus-1 susceptibility as a risk factor for sepsis, with cytomegalovirus susceptibility elevating severity: insights from a bidirectional Mendelian randomization study
Authors: Shi Wenjun , Lin Qiao , Zhang Meng , Ouyang Nengtai , Zhang Yin , Yang Zhengfei 
Published: April 2024

ABSTRACT

Objective
We conducted a two-sample bidirectional Mendelian randomization (MR) study to investigate the causal relationships between herpes viruses and sepsis.

Methods
Publicly available genome-wide association study (GWAS) data were used. Four viruses, HSV-1, HSV-2, EBV and CMV, were selected, with serum positivity and levels of antibody in serum as the herpes virus data.

Results
In forward MR, susceptibility to HSV-1 was a risk factor for sepsis. The susceptibility to CMV showed a severity-dependent effect on sepsis and was a risk factor for the 28-day mortality from sepsis, and was also a risk factor for 28-day sepsis mortality in critical care admission. EBV EA-D antibody level after EBV infection was a protective factor for 28-day sepsis mortality in critical care admission, and CMV pp28 antibody level was a risk factor for 28-day sepsis mortality in critical care admission. No statistically significant causal relationships between HSV-2 and sepsis were found. No exposures having statistically significant association with sepsis critical care admission as an outcome were found. In reverse MR, the sepsis critical care admission group manifested a decrease in CMV pp52 antibody levels. No causal relationships with statistical significance between sepsis exposure and other herpes virus outcomes were found.

Conclusions
Our study identifies HSV-1 susceptibility as a sepsis risk, with CMV susceptibility elevating severity. Varied effects of EBV and CMV antibodies on sepsis severity are noted. Severe sepsis results in a decline in CMV antibody levels. Our results help prognostic and predictive enrichment and offer valuable information for precision sepsis treatment.
Endogenous β3-adrenergic receptor activation alleviates sepsis-induced cardiomyocyte apoptosis via PI3K/Akt signaling pathway
Authors: Xing Yun , Tian Tian , Zhang Xue , Yang Duomeng , Zhang Chanjuan , Wang Miao , Wang Yiyang , Luo Tao , Wang Zhi , Wang Huadong , Li Hongmei 
Published: April 2024

ABSTRACT
β3-adrenergic receptor (β3-AR) has been proposed as a new therapy for several myocardial diseases. However, the effect of β3-AR activation on sepsis-induced myocardial apoptosis is unclear. Here, we investigated the effect of β3-AR activation on the cardiomyocyte apoptosis and cardiac dysfunction in cecal ligation and puncture (CLP)-operated rats and lipopolysaccharide (LPS)-treated cardiomyocytes. We found that β3-AR existed both in adult rat ventricular myocytes (ARVMs) and H9c2 cells. The expression of β3-AR was upregulated in LPS-treated ARVMs and the heart of CLP rats. Pretreatment with β3-AR agonist, BRL37344, inhibited LPS-induced cardiomyocyte apoptosis and caspase-3, -8 and -9 activation in ARVMs. BRL37344 also reduced apoptosis and increased the protein levels of PI3K, p-AktSer473 and p-eNOSSer1177 in LPS-treated H9c2 cells. Inhibition of PI3K using LY294002 abolished the inhibitory effect of BRL37344 on LPS-induced caspase-3, -8, and -9 activation in H9c2 cells. Furthermore, administration of β3-AR antagonist, SR59230A (5 mg/kg), significantly decreased the maximum rate of left ventricular pressure rise (+dP/dt) in CLP-induced septic rats. SR59230A not only increased myocardial apoptosis, reduced p-AktSer473 and Bcl-2 contents, but also increased mitochondrial Bax, cytoplasm cytochrome c, cleaved caspase-9 and cleaved caspase-3 levels of the myocardium in septic rats. These results suggest that endogenous β3-AR activation alleviates sepsis-induced cardiomyocyte apoptosis via PI3K/Akt signaling pathway and maintains intrinsic myocardial systolic function in sepsis.
OMX: A NOVEL OXYGEN DELIVERY BIOTHERAPEUTIC IMPROVES OUTCOMES IN AN OVINE MODEL OF CONTROLLED HEMORRHAGIC SHOCK
Authors: Maltepe Emin , Smith Michael , Boehme Jason , Datar Sanjeev A. , Hutchings Rachel S. , Vento Christian A. , Manzoor Hadiya , Loucks Alexandra , Winger Jonathan A. , Fineman Jeffrey R. 
Published: April 2024

ABSTRACT
Hemorrhagic shock is a major source of morbidity and mortality worldwide. While whole blood or blood product transfusion is a first-line treatment, maintaining robust supplies presents significant logistical challenges, particularly in austere environments. OMX is a novel nonhemoglobin (Hb)-based oxygen carrier derived from the H-NOX (heme-nitric oxide/oxygen binding) protein family. Because of their engineered oxygen (O2) affinities, OMX proteins only deliver O2 to severely hypoxic tissues. Additionally, unlike Hb-based oxygen carriers, OMX proteins do not scavenge nitric oxide in the vasculature. To determine the safety and efficacy of OMX in supporting tissue oxygen delivery and cardiovascular function in a large animal model of controlled hemorrhage, 2–3-week-old lambs were anesthetized, intubated, and mechanically ventilated. Hypovolemic shock was induced by acute hemorrhage to obtain a 50% reduction over 30 min. Vehicle (n = 16) or 400 mg/kg OMX (n = 13) treatment was administered over 15 min. Hemodynamics, arterial blood gases, and laboratory values were monitored throughout the 6-h study. Comparisons between groups were made using t tests, Wilcoxon rank sum test, and Fisher’s exact test. Survival was assessed using Kaplan-Meier curves and the log-rank test. We found that OMX was well-tolerated and significantly improved lactate and base deficit trends, and hemodynamic indices (P < 0.05). Median survival time was greater in the OMX-treated group (4.7 vs. 6.0 h, P < 0.003), and overall survival was significantly increased in the OMX-treated group (25% vs. 85%, P = 0.004). We conclude that OMX is well-tolerated and improves metabolic, hemodynamic, and survival outcomes in an ovine model of controlled hemorrhagic shock.
INHIBITORS OF INORGANIC POLYPHOSPHATE AND NUCLEIC ACIDS ATTENUATE IN VITRO THROMBIN GENERATION IN PLASMA FROM TRAUMA PATIENTS
Authors: MacArthur Taleen A. , Goswami Julie , Navarro Sergio M. , Vappala Sreeparna , La Chanel C. , Yudin Nikoli , Zietlow John , Smith Stephanie A. , Morrissey James H. , Spears Grant M. , Bailey Kent R. , Dong Jing-Fei , Kozar Rosemary A. , Kizhakkedathu Jayachandran N. , Park Myung S. 
Published: April 2024

ABSTRACTBackground:Inorganic polyphosphate (polyP) is a procoagulant polyanion. We assessed the impact of polyP inhibition on thrombin generation after trauma using the novel polyP antagonists, macromolecular polyanion inhibitor 8 (MPI 8), and universal heparin reversal agent 8 (UHRA-8).Methods:Plasma thrombin generation (calibrated automated thrombogram, CAT), in 56 trauma patients and 39 controls +/− MPI 8 and UHRA-8 (50 μg/mL), was expressed as lag time (LT, minutes), peak height (PH, nM), and time to peak (ttPeak, minutes), with change in LT (ΔLT) and change in ttPeak (ΔttPeak) quantified. Results expressed in median and quartiles [Q1, Q3], Wilcoxon matched-pairs testing,P< 0.05 significant.Results:Trauma patients had greater baseline PH than controls (182.9 [121.0, 255.2]; 120.5 [62.1, 174.8],P< 0.001). MPI 8 treatment prolonged LT and ttPeak in trauma (7.20 [5.88, 8.75]; 6.46 [5.45, 8.93],P= 0.020; 11.28 [8.96, 13.14]; 11.00 [8.95, 12.94],P= 0.029) and controls (7.67 [6.67, 10.50]; 6.33 [5.33, 8.00],P< 0.001; 13.33 [11.67, 15.33]; 11.67 [10.33, 13.33],P< 0.001). UHRA-8 treatment prolonged LT and ttPeak and decreased PH in trauma (9.09 [7.45, 11.33]; 6.46 [5.45, 8.93]; 14.02 [11.78, 17.08]; 11.00 [8.95, 12.94]; 117.4 [74.5, 178.6]; 182.9 [121.0, 255.2]) and controls (9.83 [8.00, 12.33]; 6.33 [5.33, 8.00]; 16.67 [14.33, 20.00]; 11.67 [10.33, 13.33]; 55.3 [30.2, 95.9]; 120.5 [62.1, 174.8]), allP< 0.001. Inhibitor effects were greater for controls (greater ΔLT and ΔttPeak for both inhibitors,P< 0.001).Conclusion:PolyP inhibition attenuates thrombin generation, though to a lesser degree in trauma than in controls, suggesting that polyP contributes to accelerated thrombin generation after trauma.
DIMINISHED EXPRESSION OF GLS IN CD4+ T CELLS SERVES AS A PROGNOSTIC INDICATOR ASSOCIATED WITH CUPROPTOSIS IN SEPTIC PATIENTS
Authors: Yang Jiaqi , Chen Ning , Zhao Pengyue , Yang Xingpeng , Li Yuxuan , Fu Ze , Yan Yang , Dong Ning , Li Songyan , Yao Renqi , Du Xiaohui , Yao Yongming 
Published: April 2024

ABSTRACT

Objectives: Sepsis is defined as a life-threatening disease associated with a dysfunctional host immune response. Stratified identification of critically ill patients might significantly improve the survival rate. The present study sought to probe molecular markers associated with cuproptosis in septic patients to aid in stratification and improve prognosis. Methods: We studied expression of cuproptosis-related genes (CRGs) using peripheral blood samples from septic patients. Further classification was made by examining levels of expression of these potential CRGs in patients. Coexpression networks were constructed using the Weighted Gene Coexpression Network Analysis (WGCNA) method to identify crucial prognostic CRGs. Additionally, we utilized immune cell infiltration analysis to further examine the immune status of septic patients with different subtypes and its association with the CRGs. scRNA-seq data were also analyzed to verify expression of key CRGs among specific immune cells. Finally, immunoblotting, flow cytometry, immunofluorescence, and CFSE analysis were used to investigate possible regulatory mechanisms. Results: We classified septic patients based on CRG expression levels and found significant differences in prognosis and gene expression patterns. Three key CRGs that may influence the prognosis of septic patients were identified. A decrease in GLS expression was subsequently verified in Jurkat cells, accompanied by a reduction in O-GlcNAc levels, and chelation of copper by tetrathiomolybdate could not rescue the reduction in GLS and O-GLcNAc levels. Moreover, immoderate chelation of copper was detrimental to mitochondrial function, cell viability, and cell proliferation, as well as the immune status of the host. Conclusion: We have identified novel molecular markers associated with cuproptosis, which could potentially function as diagnostic indicators for septic patients. The reversible nature of the observed alterations in FDX1 and LIAS was demonstrated through copper chelation, whereas the correlation between copper and the observed changes in GLS requires further investigation.
EFFECT OF PULMONARY ARTERY CATHETERIZATION IN PATIENTS WITH NONISCHEMIC CARDIOGENIC SHOCK: A NATIONWIDE ANALYSIS
Authors: Diaz-Arocutipa Carlos , Moreno Guillermo , Gil David Galán , Nieto Sara , Romo Martín , Vicent Lourdes 
Published: April 2024

ABSTRACT

Background: Pulmonary artery catheterization (PAC) has been widely used in critically ill patients, yielding mixed results. Prior studies on cardiogenic shock (CS) predominantly included patients with acute myocardial infarction. This study aims to examine the effect of PAC use in patients with nonischemic CS. Methods: This retrospective cohort study employed data from the National Inpatient Sample database, including weighted hospitalizations of adult patients with nonischemic CS during 2017 to 2019. In-hospital outcomes were compared between groups using inverse probability of treatment weighting. Results: A total of 303,970 patients with nonischemic CS were included, of whom 17.5% received a PAC during their hospitalization. The median age was 67 years (interquartile range: 57–77) and 61% were male. After inverse probability of treatment weighting, patients in the PAC group had significantly lower in-hospital mortality (24.8% vs. 35.3%, P < 0.001), renal replacement therapy (10.7% vs. 12.4%, P = 0.002), in-hospital cardiac arrest (7.1% vs. 9.6%, P < 0.001), and mechanical ventilation (44.6% vs. 50.4%, P < 0.001) compared to non-PAC group. In contrast, the PAC group had higher use of intra-aortic balloon pump (15.4% vs. 3.4%, P < 0.001), percutaneous ventricular assist devices (12.6% vs. 2.6%, P < 0.001), extracorporeal membrane oxygenation (3.9% vs. 2.5%, P < 0.001), and heart transplantation (2.1% vs. 0.4%, P < 0.001). Conclusion: In the real-world setting, invasive hemodynamic monitoring with PAC in patients with nonischemic CS is associated with survival benefits and a reduction in adverse events, including reduced need for renal replacement therapy, mechanical ventilation and risk of in-hospital cardiac arrest.
EFFECTS OF LEVOSIMENDAN ON DIAPHRAGMATIC DYSFUNCTION IN PATIENTS WITH SEPSIS
Authors: Wu Jia-Qian , Wang Ying-Xin , Su Dan , Shao Teng-Hao , Ding Xiao-Xu , Sun Tao , Cui Na , Yu Zhan-Biao 
Published: April 2024

ABSTRACT

Objective: In this study, our aim was to examine the effects of levosimendan on diaphragmatic dysfunction in patients with sepsis, as well as assess its impact on respiratory muscle contractility and the outcome of weaning. Methods: This was a single-blind, randomized, controlled trial. Patients with diaphragmatic dysfunction and failure of spontaneous breathing trials (SBTs) were randomly and equally assigned to the experimental and control groups. The experimental group received levosimendan at a loading dose of 6 μg/kg for 10 min, followed by a continuous infusion at 0.2 μg/kg/min. The control group received an equivalent dose of a placebo. The preadministration and postadministration respiratory mechanics parameters of the patients were recorded. Evaluation of the effect of levosimendan on patients with sepsis-induced diaphragm dysfunction comprised arterial blood gas analysis as well as ultrasound measurements of diaphragm excursion (DE), diaphragm thickness (DT), diaphragm thickening fraction (TFdi), and diaphragm-rapid shallow breathing index (D-RSBI). Results: Forty-four patients were enrolled in the study. We found that postadministration of levosimendan, the patients’ tidal volume (GCSMV) increased, whereas the D-RSBI decreased, and the partial pressure of carbon dioxide (PACO2) decreased when compared to the preadministration levels. Additionally, following levosimendan administration, patients showed increased DE and pressure support (PS) when compared to before administration (1.14 ± 0.177 vs. 1.22 ± 0.170 cm and 0.248 ± 0.03 vs. 0.284 ± 0.06, respectively) and decreased D-RSBI (22.76 ± 6.14 vs. 20.06 ± 6.04, respectively), all of which were statistically significant (P < 0.05). In contrast, in the control group of patients, there were no statistically significant differences in the postadministration levels of DE, TFdi, and D-RSBI as compared to the preadministration period (P > 0.05). Furthermore, in terms of weaning outcomes, we did not find any statistically significant difference in the number of patients in the two groups who eventually underwent weaning (P = 0.545). Conclusion: In this study, we found that levosimendan enhanced diaphragm contractile function. However, further investigations are required to explore its effect on weaning outcomes in patients undergoing mechanical ventilation.
Disparities in Access to Outpatient Surgery Related to Removal of Procedures from Medicare’s Inpatient Only List
Authors: Tsai Thomas C. , Brownlee Sarah A. , Dai Dannie , Soto Mark , Rosenthal Ning , Orav E. John , Frakt Austin B. , Figueroa Jose F. 
Published: April 2024

Objective:
We assessed the shift from inpatient to outpatient surgical care related to changes to the Inpatient Only List in 2020 and 2021 compared to 2019.

Summary Background Data:
The extent to which procedures shift from the inpatient to outpatient setting following removal from Medicare’s Inpatient Only List is unknown. Many health systems also encouraged a shift from inpatient to outpatient surgery during the COVID-19 pandemic. Assessing the relative change in outpatient surgical utilization for procedures removed from the Inpatient Only List during COVID-19 would provide empirical data on whether reimbursement policy changes or inpatient capacity needs during the pandemic were more likely to shift care from the inpatient to outpatient setting.

Methods:
We used administrative data from the PINC AI Healthcare Database across 723 hospitals to determine the within-facility relative change in outpatient vs inpatient procedural volume in 2020 and 2021 compared to 2019 using a multivariable conditional fixed-effects Poisson regression model. We also assessed whether outpatient surgical utilization varied by race and ethnicity. Using a multivariable linear probability model, we assessed the absolute change in risk-adjusted 30-day complication, readmission, and mortality rates for inpatient and outpatient surgical procedures.

Results:
In 2020 and 2021 compared to 2019 respectively, there was a 5.3% (95% CI, 1.4% to 9.5%) and 41.3% (95% CI 33.1% to 50.0%) relative increase in outpatient elective procedural volume. Outpatient procedural volume increased most significantly for hip replacement which was removed from the Inpatient Only List in 2020 (increase in outpatient surgical utilization of 589.3% (95% CI, 524.9% to 660.3%)). The shift to outpatient hip replacement procedures was concentrated among White patients; in 2021, hip replacement procedural volume increased by 271.1% (95% CI, 241.2% and 303.7%) for White patients and 29.5% (95% CI, 24.4% and 34.9%) for Black patients compared to 2019 levels. There were no consistent or large changes in 30-day complication, readmission, or mortality risk in 2020 and 2021 compared to 2019.

Conclusion:
There was a modest increase in elective outpatient surgeries and a pronounced increase in outpatient orthopedic surgeries which were removed from the Inpatient Only List during the COVID-19 pandemic. Utilization of outpatient surgical procedures was concentrated among White patients.
Group A Streptococcus isolated in Guyana with reduced susceptibility toβ-lactam antibiotics
Authors: Kalladeen Melissa , Cheddie Paul , Akpaka Patrick Eberechi 
Published: April 2024

Introduction: Streptococcus pyogenes (Group A streptococci [GAS]) is the causative agent of pharyngitis and various other syndromes involving cellulitis, streptococcal toxic shock syndrome (STSS) and necrotising fasciitis. Although the prevalence of GAS infections globally remains high, necessitating the widespread use of [[EQUATION]]-lactam antibiotics, GAS has remained largely susceptible to these agents. However, there have been several reports of GAS with reduced susceptibility harbouring mutations in genes for penicillin-binding proteins (PBPs). The objectives of this study were to examine the in vitro -lactam susceptibility patterns of Group A streptococci, determine the prevalence of drug resistance and ascertain whether such resistance could be attributed to mutations in specific PBP genes.

Methods: In this study, we sought to use Sanger sequencing to identify mutations in PBP genes of Streptococcus pyogenes isolated from patients that required inpatient and outpatient care that could confer reduced PBP affinity for penicillin and/or cephalosporin antibiotics. All isolates were screened for susceptibility to penicillin, amoxicillin, and cefazolin using E-test strips.

Results: While there were no documented cases of reduced susceptibility to penicillin or amoxicillin. Thirteen isolates had reduced susceptibility against cefazolin. Examination of pbp1a by Sanger sequencing revealed several isolates with single amino acid substitutions, which could potentially reduce the affinity of PBP 1A for cefazolin and possibly other first-generation cephalosporins.

Conclusion: Penicillin and penicillin-derived antibiotics remain effective treatment options for GAS infections, but active surveillance is needed to monitor for changes to susceptibility patterns against these and other antibiotics and understand the genetic mechanisms contributing to them.