Sepsis Among Medicare Beneficiaries: 1. The Burdens of Sepsis, 2012–2018*

Buchman, Timothy G.; Simpson, Steven Q.; Sciarretta, Kimberly L.; Finne, Kristen; Sowers, Nicole; Collier, Michael; Chavan, Saurabh; Oke, Ibijoke; Pennini, Meghan E.; Santhosh, Aathira; Wax, Marie; Woodbury, Robyn; Chu, Steve; Merkeley, Tyler; Disbrow, Gary L.; Bright, Rick A.; MaCurdy, Thomas; Kelman, Jeffrey A.

doi:10.1097/ccm.0000000000004224

Cited by 199 publications

(123 citation statements)

References 26 publications

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“…This reaction leads to aberrant immune responses, and if not diagnosed and treated early after its onset, it may limit survival by inducing coagulopathy, altered microvasculature, and dysregulation of the host’s metabolism and organ function ( Lewis et al, 2016 ; Bermudes et al, 2018 ; Cheng et al, 2016 ; Levi and van der Poll, 2017 ; Schneck et al, 2017 ; McDonald et al, 2017 ; Kidokoro et al, 1996 ). Sepsis accounts for one in three hospital deaths in the USA and millions of deaths each year globally, highlighting its hazard to public health ( Rhee et al, 2017 ; Buchman et al, 2020 ). The high mortality rate associated with sepsis reflects the lack of clinically viable molecular-based therapeutic target.…”

Section: Introductionmentioning

confidence: 99%

Dichloroacetate reverses sepsis-induced hepatic metabolic dysfunction

Mainali

Zabalawi

Long

et al. 2021

eLife

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Metabolic reprogramming between resistance and tolerance occurs within the immune system in response to sepsis. While metabolic tissues such as the liver are subject to damage during sepsis, how their metabolic and energy reprogramming ensures survival is unclear. Employing comprehensive metabolomic, lipidomic, and transcriptional profiling in a mouse model of sepsis, we show that hepatocyte lipid metabolism, mitochondrial TCA energetics, and redox balance are significantly reprogramed after cecal ligation and puncture (CLP). We identify increases in TCA cycle metabolites citrate, cis-aconitate, and itaconate with reduced fumarate and triglyceride accumulation in septic hepatocytes. Transcriptomic analysis of liver tissue supports and extends the hepatocyte findings. Strikingly, the administration of the pyruvate dehydrogenase kinase (PDK) inhibitor dichloroacetate (DCA) reverses dysregulated hepatocyte metabolism and mitochondrial dysfunction. In summary, our data indicate sepsis promotes hepatic metabolic dysfunction and that targeting the mitochondrial PDC/PDK energy homeostat rebalances transcriptional and metabolic manifestations of sepsis within the liver.

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Section: Introductionmentioning

confidence: 99%

Dichloroacetate reverses sepsis-induced hepatic metabolic dysfunction

Mainali

Zabalawi

Long

et al. 2021

eLife

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“…Combined with subsequent skilled nursing facility admission, the total Medicare cost is estimated to be $41. 5 1 1billion [13]. Due to the critical nature of sepsis, the associated morbidity and mortality, and the resulting economic impact on healthcare, prompt recognition of the condition and enactment of early therapeutic interventions in severe sepsis and septic shock are important.…”

Section: Introductionmentioning

confidence: 99%

The Role of Brain Natriuretic Peptide as a Prognostic Marker for Sepsis

Bhandari

Cunningham

2020

Cureus

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Brain natriuretic peptide (BNP) is a neurohormone released in response to volume expansion and increased pressure. It is commonly used to assist in the diagnosis and management of heart failure. BNP can also play an important role as a biomarker in septic shock; however, elevations of BNP in conditions other than sepsis or cardiac dysfunction limits its use as the sole prognostic marker in patients hospitalized with sepsis. Further relationships regarding laboratory value and correlation with severity of illness need to be established with larger prospective studies to develop consensus regarding a cutoff point for optimum sensitivity and specificity in predicting in-hospital mortality related to sepsis.

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“…Sepsis hospitalizations are associated with substantial morbidity, mortality, and costs to the healthcare system ( 1 , 2 ). However, there is substantial variability in how sepsis is diagnosed and coded ( 3 – 5 ).…”

mentioning

confidence: 99%

Prevalence and Clinical Characteristics of Patients With Sepsis Discharge Diagnosis Codes and Short Lengths of Stay in U.S. Hospitals

Kuye

Anand

Chan

et al. 2021

Critical Care Explorations

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Objectives: Some patients diagnosed with sepsis have very brief hospitalizations. Understanding the prevalence and clinical characteristics of these patients may provide insight into how sepsis diagnoses are being applied as well as the breadth of illnesses encompassed by current sepsis definitions. Design: Retrospective observational study. Setting: One-hundred ten U.S. hospitals in the Cerner HealthFacts dataset (primary cohort) and four hospitals in Eastern Massachusetts (secondary cohort used for detailed medical record reviews). Patients: Adults hospitalized from April 2016 to December 2017. Interventions: None. Measurements and Main Results: We identified hospitalizations with International Classification of Diseases, 10th Edition codes for sepsis (including sepsis, septicemia, severe sepsis, and septic shock) and compared “short stay sepsis” patients (defined as discharge alive within 3 d) versus nonshort stay sepsis patients using detailed electronic health record data. In the Cerner cohort, 67,733 patients had sepsis discharge diagnosis codes, including 6,918 (10.2%) with short stays. Compared with nonshort stay sepsis patients, short stay patients were younger (median age 60 vs 67 yr) and had fewer comorbidities (median Elixhauser score 5 vs 13), lower rates of positive blood cultures (8.2% vs 24.1%), lower rates of ICU admission (6.2% vs 31.6%), and less frequently had severe sepsis/septic shock codes (13.5% vs 36.6%). Almost all short stay and nonshort stay sepsis patients met systemic inflammatory response syndrome criteria at admission (84.5% and 87.5%, respectively); 47.2% of those with short stays had Sequential Organ Failure Assessment scores of 2 or greater at admission versus 73.2% of those with longer stays. Findings were similar in the secondary four-hospital cohort. Medical record reviews demonstrated that physicians commonly diagnosed sepsis based on the presence of systemic inflammatory response syndrome criteria, elevated lactates, or positive blood cultures without concurrent organ dysfunction. Conclusions: In this large U.S. cohort, one in 10 patients coded for sepsis were discharged alive within 3 days. Although most short stay patients met systemic inflammatory response syndrome criteria, they met Sepsis-3 criteria less than half the time. Our findings underscore the incomplete uptake of Sepsis-3 definitions, the breadth of illness severities encompassed by both traditional and new sepsis definitions, and the possibility that some patients with sepsis recover very rapidly.

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Sepsis Among Medicare Beneficiaries: 1. The Burdens of Sepsis, 2012–2018*

Cited by 199 publications

References 26 publications

Dichloroacetate reverses sepsis-induced hepatic metabolic dysfunction

Dichloroacetate reverses sepsis-induced hepatic metabolic dysfunction

The Role of Brain Natriuretic Peptide as a Prognostic Marker for Sepsis

Prevalence and Clinical Characteristics of Patients With Sepsis Discharge Diagnosis Codes and Short Lengths of Stay in U.S. Hospitals

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