Discovery medicine
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Biliary tract cancers (BTC), which include cholangiocarcinoma (both intra- and extrahepatic) and gallbladder, represent a heterogeneous group of malignancies with relatively low-incidence and poor prognosis. Therapeutic options for BTC patients at advanced stage are severely limited and palliative chemotherapy remains the maintreatment option. ⋯ Thus, in the near term, the individual molecular alterations of the disease rather than the anatomic location will likely drive the design of clinical trials. In this review, we summarize recent molecular discoveries in BTC with a special emphasis on the most promising therapeutic targets, ultimately providing an update on current and future directions in the management of this disease.
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Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies without effective screening strategy during the early stage. Therefore, a novel screening panel was identified based on potential biomarkers associated with PDAC using the gene expression profile. The dataset GSE15471, which was downloaded from the Gene Expression Omnibus (GEO) database, included matching pairs of normal and tumor tissue samples from the resected pancreas of 39 pancreatic cancer patients. ⋯ Gene Expression Profiling Interactive Analysis (GEPIA) survival analysis showed that high expressions of KRT7, KRT19, SEMA3C, ITGA2, MYOF, and ANXA1 may predict poor survival outcome in PDAC. Finally, Oncomine confirmed that the high expressions of these genes were strongly related to cancer grade. These hub genes and regulators straightened out the molecular pathways and recurrence mechanisms in PDAC and could be used as targets for PDAC's diagnosis, treatment, and prognostic prediction.
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The easy liver fibrosis test (eLIFT) is a novel index to assess advanced liver fibrosis in chronic liver diseases. We aimed to investigate the diagnostic accuracy of eLIFT for advanced liver fibrosis in patients with chronic hepatitis B (CHB). ⋯ eLIFT as a novel index can predict advanced liver fibrosis with a moderate sensitivity and accuracy in CHB patients. eLIFT, though having similar diagnostic values of advanced liver fibrosis compared to more complex existing tools such as APRI, FIB-4, GPR, and RPR in CHB patients, has the advantage of clarity of generation and ease of application and has the potential of being widely used by hepatologists.
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The cold pressor test (CPT) has been used in experimental paradigms to measure pain tolerance. It is used clinically to evaluate for opioid-induced hyperalgesia (OIH), as part of the clinical evaluation of fibromyalgia, to document reversal of OIH by low dose naltrexone (LDN), and to document the clinical response of fibromyalgia to LDN. ⋯ CPT is shown to be an objective test of pain tolerance with clinical applications: evaluation of OIH, evaluation of fibromyalgia, reversal of OIH, protracted withdrawal with LDN, and amelioration of fibromyalgia with LDN.
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Prescribing medications safely and effectively in older adults is a complex process. This review discusses challenges with medication prescribing in older adults and outlines a holistic approach to medication management in older adults. Well-known challenges including the alterations in pharmacokinetics and pharmacodynamics that often occur with aging are discussed. ⋯ Newer approaches, including deprescribing, pharmacogenomics, and the future potential for senolytic therapy are also discussed. All healthcare providers should consider these challenges when prescribing medications in older adults. Choosing a drug that fits both a patient's pathophysiology and biology, avoiding drugs with significant side effects, titrating doses, and deprescribing are all critical in optimizing medication therapy.