Currently, no blood biomarker that specifically indicates injury to the proximal tubule of the kidney has been identified. Kidney injury molecule-1 (KIM-1) is highly upregulated in proximal tubular cells following kidney injury. The ectodomain of KIM-1 is shed into the lumen, and serves as a urinary biomarker of kidney injury. We report that shed KIM-1 also serves as a blood biomarker of kidney injury. Sensitive assays to measure plasma and serum KIM-1 in mice, rats, and humans were developed and validated in the current study. Plasma KIM-1 levels increased with increasing periods of ischemia (10, 20, or 30 minutes) in mice, as early as 3 hours after reperfusion; after unilateral ureteral obstruction (day 7) in mice; and after gentamicin treatment (50 or 200 mg/kg for 10 days) in rats. In humans, plasma KIM-1 levels were higher in patients with AKI than in healthy controls or post-cardiac surgery patients without AKI (area under the curve, 0.96). In patients undergoing cardiopulmonary bypass, plasma KIM-1 levels increased within 2 days after surgery only in patients who developed AKI (P,0.01). Blood KIM-1 levels were also elevated in patients with CKD of varous etiologies. In a cohort of patients with type 1 diabetes and proteinuria, serum KIM-1 level at baseline strongly predicted rate of eGFR loss and risk of ESRD during 5-15 years of follow-up, after adjustment for baseline urinary albuminto-creatinine ratio, eGFR, and Hb1Ac. These results identify KIM-1 as a blood biomarker that specifically reflects acute and chronic kidney injury.
Endoscopic ultrasound (EUS) has become an indispensable modality for the assessment of the gastrointestinal tract and adjacent structures since its origin in the 1980s. Following the development of the linear echoendoscope, EUS has evolved from a purely diagnostic modality to a sophisticated tool for intervention, with numerous luminal, pancreaticobiliary, and hepatic applications. Broadly, these applications may be subdivided into three categories: transluminal drainage or access procedures, injection therapy, and EUS-guided liver interventions. Transluminal drainage or access procedures include management of pancreatic fluid collection, EUS-guided biliary drainage, EUS-guided bile duct drainage, EUS-guided pancreatic duct drainage, and enteral anastomosis formation. Injection therapies include therapeutic EUS-guided injections for management of malignancies accessible by EUS. EUS-guided liver applications include EUS-guided liver biopsy, EUS-guided portal pressure gradient measurement, and EUS-guided vascular therapies. In this review, we discuss the origins of each of these EUS applications, evolution of techniques leading to the current status, and future directions of EUS-guided interventional therapy.
Esophageal cancer (ECA) affects 1 in 125 men and 1 in 417 for women and accounts for 2.6% of all cancer related deaths in the United States. The associated survival rate depends on the stage of the cancer at the time of diagnosis, making adequate work up and staging imperative. The 5-year survival rate for localized disease is 46.4%, regional disease is 25.6%, and distant/metastatic disease is 5.2%. Additionally, treatment is stage-dependent, making staging all that much important. For nonmetastatic transmural tumors (T3) and/or those that have locoregional lymph node involvement (N), neoadjuvant therapy is recommended. Conversely, for those who have earlier tumors, upfront surgical resection is reasonable. While positron emission tomography/computed tomography and other cross sectional imaging modalities are exceptional for detecting distant disease, they are inaccurate in staging locoregional disease. Endoscopic ultrasound (EUS) has played a key role in the locoregional (T and N) staging of newly diagnosed ECA and has an evolving role in restaging after neoadjuvant therapy. There is even data to support that the use of EUS facilitates proper triaging of patients and may ultimately save money by avoiding unnecessary or futile treatment. This manuscript will review the current role of EUS on staging and restaging of ECA.
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