ABSTRACT
PURPOSE OF REVIEW: Following cardiac transplantation, patients have an increased risk of developing cardiac allograft vasculopathy and atherosclerotic cardiovascular disease. Therefore, aggressive lipid management is indicated. Some patients do not achieve optimal lipid profiles with statin monotherapy, however, or discontinue statins due to intolerance. In this review, we investigated the use of PCSK9 inhibitors as an alternative treatment for hyperlipidemia following cardiac transplantation. RECENT FINDINGS: Nine published articles were identified that included 110 patients treated with alirocumab or evolocumab after cardiac transplantation. PCSK9 inhibitors were tolerated by all patients, and each study demonstrated an effective reduction of low-density lipoprotein ranging from 40 to 87% decrease from baseline. In our study, the 110 patients from literature review were added to a cohort of 7 similar patients from our institution for combined analysis. This report supports that PCSK9 inhibitors should be considered following cardiac transplantation when conventional medial therapy is not tolerated or ineffective.
Subject(s)
Cardiovascular Diseases , Heart Failure , Heart Transplantation , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal/pharmacology , Cardiovascular Diseases/prevention & control , Heart Failure/complications , Heart Transplantation/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Lipids , PCSK9 Inhibitors , Proprotein Convertase 9 , Retrospective StudiesABSTRACT
PURPOSE: Scrub typhus, caused by Orientia tsutsugamushi (O. tsutsugamushi) present nonspecific clinical features during manifestation of acute undifferentiated febrile illness (AUFI) to render its early diagnosis difficult. Accordingly, this study was undertaken to assess an in-house groEL PCR versus IgM ELISA for the diagnosis of scrub typhus and to genotypically characterise the randomly selected scrub typhus positive cases. METHODS: Blood samples, collected from two hundred twenty one (221) AUFI cases were subjected to groEL PCR and IgM ELISA for diagnosis of scrub typhus. Eleven randomly selected PCR positive cases were processed for DNA sequencing to determine the genetic diversity of O. tsutsugamushi in Chhattisgarh. RESULTS: Scrub typhus prevalence of 35.2% were detected among AUFI cases using both in-house groEL PCR and IgM ELISA. PCR alone showed sensitivity, specificity, positive and negative predictive values of 66.6% (CI: 55.08-76.94), 100% (CI: 90 to 100),100% (CI: 93.15 to 100) and 57.37% (CI: 44.05 to 69.96) while for IgM ELISA, these parameters were 62.8% (CI: 51.13-73.50), 100% (CI: 90 to 100), 100% (CI: 92.75 to 100) and 54.68% (CI: 41.75 to 67.18) respectively. PCR and ELISA could detect scrub typhus in 37.2% and 33.3% cases, when tested alone. groEL PCR detected the O. tsutsugamushi throughout the course of infection. Phylogenetic analysis depicted 5 of 11 positive cases belonged to Kuroki, Japan strain of O. tsutsugamushi, followed by Gilliam and Karp strain in 4 and 2 cases respectively. CONCLUSION: Scrub typhus should be considered in differential diagnosis of AUFI. groEL PCR may aid on to IgM ELISA test for optimum laboratory diagnosis of scrub typhus by its implementation especially in seronegative cases. Predominance of Kuroki-like strain followed by Gillian and Karp strains of O. tsutsugamushi in Chhattisgarh confirm variable geographical distribution of O. tsutsugamushi and provide the baseline epidemiological data which will eventually be used to help the researchers for developing better diagnostic tests and vaccine covering the predominant genotypes.