Pulmonary tuberculosis presenting with aortic pseudoaneurysm, diffuse alveolar hemorrhage, and cardiomyopathy: Is there an intriguing relationship?

A 22-year-old Chinese man presented with fever, cough, hoarseness, neck pain, acute heart failure and hemoptysis. Pulmonary tuberculosis was proved by sputum culture. Chest imaging showed an aortic arch pseudoaneurysm and bilateral ground glass opacities. Echocardiography confirmed cardiomyopathy. With anti-TB drugs, high-dose prednisone and surgery, the life of this patient was successfully prolonged for more than four months. The concomitant disorders of aortic pseudoaneurysm, alveolar hemorrhage and cardiomyopathy in pulmonary tuberculosis are intriguing. We postulate that immune-mediated small vessel vasculitis triggered by pathogens plays an important role in the pathogenesis of this disease, rather than a direct TB infection.

Global prediction system for COVID-19 pandemic

The outbreak of a novel coronavirus(SARS-CoV-2)has resulted in a worldwide pandemic infecting over 5.9 million people[1].This positive-strand RNA virus can cause severe respiratory distress syndrome in humans(COVID-19),with over 364,000 deaths between December 2019 and May 30,2020[1,2].To combat this pandemic,the World Health Organization(WHO)is coordinating global efforts on surveillance,epidemiology,mathematical model-ing,diagnostics,treatment and control,and has issued interim guidance to countries.Nevertheless,this is a difficult situation and the number of cases is rapidly increasing globally.The tempo-ral evolution and the spatial spread of this virus have also raised serious concerns about the future trajectory of this outbreak.

Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development

Drug metabolism and pharmacokinetics(DMPK) is an important branch of pharmaceutical sciences.The nature of ADME(absorption,distribution,metabolism,excretion) and PK(pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems.Tremendous progress has been made in the past decade,not only in the characterization of physiochemical properties of drugs that influence their ADME,target organ exposure,and toxicity,but also in the identification of design principles that can minimize drug-drug interaction(DDI) potentials and reduce the attritions.The importance of membrane transporters in drug disposition,efficacy,and safety,as well as the interplay with metabolic processes,has been increasingly recognized.Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs,such as peptides,oligonucleotides,and antibody-drug conjugates,necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties.In this review,we highlight some of the most notable advances in the last decade,and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.