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Annual Review of Medicine

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https://read.qxmd.com/read/30477394/entering-the-modern-era-of-gene-therapy
#1
Xavier M Anguela, Katherine A High
Gene therapies are gaining momentum as promising early successes in clinical studies accumulate and examples of regulatory approval for licensing increase. Investigators are advancing with cautious optimism that effective, durable, and safe therapies will provide benefit to patients-not only those with single-gene disorders but those with complex acquired diseases as well. While the strategies being translated from the lab to the clinic are numerous, this review focuses on the clinical research that has forged the gene therapy field as it currently stands...
November 26, 2018: Annual Review of Medicine
https://read.qxmd.com/read/30477393/non-vitamin-k-antagonist-oral-anticoagulants-in-the-treatment-of-atrial-fibrillation
#2
Alexander C Fanaroff, E Magnus Ohman
Atrial fibrillation (AF) increases a patient's stroke risk four- to five-fold. Anticoagulation with the vitamin K antagonist (VKA) warfarin reduces the risk of stroke by 67%, but warfarin carries a significant risk of major bleeding and has unpredictable pharmacodynamics with a narrow therapeutic window, necessitating frequent monitoring of its anticoagulant effect. The non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban provide more predictable anticoagulant activity than warfarin with a lower risk of major bleeding, and each is noninferior to warfarin for the prevention of stroke...
November 26, 2018: Annual Review of Medicine
https://read.qxmd.com/read/30691375/prostate-magnetic-resonance-imaging-lesion-detection-and-local-staging
#3
Baris Turkbey, Peter L Choyke
Dramatic changes in the use of prostate magnetic resonance imaging (MRI) have occurred in the last decade. The recognition that MRI detects and localizes cancers with reasonable accuracy led to the development of directed biopsies. These image-guided biopsies have a higher sensitivity for clinically significant cancers and a lower sensitivity for indolent disease. Prospective trials provide level 1 evidence supporting the use of prostate MRI. For local staging, while the specificity of prostate MRI is high, its sensitivity is lacking for microscopic extraprostatic extension...
January 27, 2019: Annual Review of Medicine
https://read.qxmd.com/read/30691374/harnessing-tumor-mutations-for-truly-individualized-cancer-vaccines
#4
Mathias Vormehr, Özlem Türeci, Ugur Sahin
T cells are key effectors of anticancer immunity. They are capable of distinguishing tumor cells from normal ones by recognizing major histocompatibility complex-bound cancer-specific peptides. Accumulating evidence suggests that peptides associated with T cell-mediated tumor rejection arise predominantly from somatically mutated proteins and are unique to every patient's tumor. Knowledge of an individual's cancer mutanome (the entirety of cancer mutations) allows harnessing this enormous tumor cell-specific repertoire of highly immunogenic antigens for individualized cancer vaccines...
January 27, 2019: Annual Review of Medicine
https://read.qxmd.com/read/30691373/imaging-of-prostate-specific-membrane-antigen-with-small-molecule-pet-radiotracers-from-the-bench-to-advanced-clinical-applications
#5
Steven P Rowe, Michael A Gorin, Martin G Pomper
In recent years, small-molecule inhibitors of prostate-specific membrane antigen (PSMA) labeled with radionuclides that allow for positron emission tomography (PET) imaging have been extensively studied in many clinical contexts in men with prostate cancer (PCa). The high sensitivity and specificity of these agents for identifying sites of PCa has quickly led to their widespread adoption as a de facto clinical standard of care throughout much of the world. PSMA-targeted PET radiotracers have been particularly well-studied in preoperatively staging men with high-risk PCa, evaluating biochemical recurrence following definitive therapy, and guiding metastasis-directed therapy in patients suspected of having oligorecurrent/oligometastatic disease...
January 27, 2019: Annual Review of Medicine
https://read.qxmd.com/read/30691372/postpartum-depression-pathophysiology-treatment-and-emerging-therapeutics
#6
Donna E Stewart, Simone N Vigod
Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is vital to identify best treatments for optimal maternal, infant, and family outcomes. New understanding of PPD pathophysiology and emerging therapeutics offer the potential for new ways to add to current medications, somatic treatments, and evidence-based psychotherapy...
January 27, 2019: Annual Review of Medicine
https://read.qxmd.com/read/30691371/progress-in-understanding-and-treating-idiopathic-pulmonary-fibrosis
#7
Jonathan A Kropski, Timothy S Blackwell
This is a time of substantial progress in the evaluation and care of patients with idiopathic pulmonary fibrosis (IPF). In addition to the approval and widespread availability of the first IPF-specific therapies, there have been improvements in imaging interpretation and lung biopsy methods to enable more expeditious and more accurate diagnosis. Recent advances in identifying genetic factors that underlie susceptibility to IPF and affect prognosis have raised the possibility of personalized therapeutic approaches in the future...
January 27, 2019: Annual Review of Medicine
https://read.qxmd.com/read/30691370/abbreviated-magnetic-resonance-imaging-mri-for-breast-cancer-screening-rationale-concept-and-transfer-to-clinical-practice
#8
Christiane K Kuhl
Given the increasing understanding of cancer as a heterogeneous group of diseases, detection methods should offer a sensitivity profile that ensures perfect sensitivity for biologically important cancers while screening out self-limiting pseudocancers. However, mammographic screening is biased toward detection of ductal carcinoma in situ and slowly growing cancers-and thus frequently fails to detect biologically aggressive cancers. This explains the persistently high rates of interval cancers and high rates of breast cancer mortality observed in spite of decades of mammographic screening...
January 27, 2019: Annual Review of Medicine
https://read.qxmd.com/read/30691369/new-drugs-in-multiple-myeloma
#9
Chutima Kunacheewa, Robert Z Orlowski
Multiple myeloma is diagnosed in over 100,000 patients each year worldwide, has an increasing incidence and prevalence in many regions, and follows a relapsing course, making it a significant and growing healthcare challenge. Recent basic, translational, and clinical studies have expanded our therapeutic armamentarium, which now consists of alkylating agents, corticosteroids, deacetylase inhibitors, immunomodulatory agents, monoclonal antibodies, and proteasome inhibitors. New drugs in these categories, and additional agents, including both small and large molecules, as well as cellular therapies, are under development that promise to further expand our capabilities and bring us closer to the cure of this plasma cell dyscrasia...
January 27, 2019: Annual Review of Medicine
https://read.qxmd.com/read/30691368/dna-methylation-and-susceptibility-to-autism-spectrum-disorder
#10
Martine W Tremblay, Yong-Hui Jiang
The prevalence of autism spectrum disorder (ASD) has been increasing steadily over the last 20 years; however, the molecular basis for the majority of ASD cases remains unknown. Recent advances in next-generation sequencing and detection of DNA modifications have made methylation-dependent regulation of transcription an attractive hypothesis for being a causative factor in ASD etiology. Evidence for abnormal DNA methylation in ASD can be seen on multiple levels, from genetic mutations in epigenetic machinery to loci-specific and genome-wide changes in DNA methylation...
January 27, 2019: Annual Review of Medicine
https://read.qxmd.com/read/30691367/therapeutic-antisense-oligonucleotides-are-coming-of-age
#11
C Frank Bennett
The first published description of therapeutic applications of antisense oligonucleotide (ASO) technology occurred in the late 1970s and was followed by the founding of commercial companies focused on developing antisense therapeutics in the late 1980s. Since the late 1980s, there has been steady progress in improving the technology platform, taking advantage of advances in oligonucleotide chemistry and formulations as well as increased understanding of the distribution and safety of ASOs. There are several approved ASO drugs and a broad pipeline in development...
January 27, 2019: Annual Review of Medicine
https://read.qxmd.com/read/30691366/ethics-of-human-genome-editing
#12
Barry S Coller
Advances in human genome editing, in particular the development of the clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 method, have led to increasing concerns about the ethics of editing the human genome. In response, the US National Academy of Sciences and the National Academy of Medicine constituted a multidisciplinary, international committee to review the current status and make recommendations. I was a member of that committee, and the core of this review reflects the committee's conclusions...
January 27, 2019: Annual Review of Medicine
https://read.qxmd.com/read/30691365/treatment-of-advanced-prostate-cancer
#13
Min Yuen Teo, Dana E Rathkopf, Philip Kantoff
The therapeutic landscape of prostate cancer has been transformed over the last decade by new therapeutics, advanced functional imaging, next-generation sequencing, and better use of existing therapies in early-stage disease. Until 2004, progression on androgen deprivation therapy for metastatic disease was treated with the addition of secondary hormonal manipulation; in the last decade, six systemic agents have been approved for the treatment of castration-resistant prostate cancer. We review clinical trials and survival benefit for these therapies and assess how the understanding of the disease shifted as these therapies were developed...
January 27, 2019: Annual Review of Medicine
https://read.qxmd.com/read/30691364/structure-based-vaccine-antigen-design
#14
Barney S Graham, Morgan S A Gilman, Jason S McLellan
Enabled by new approaches for rapid identification and selection of human monoclonal antibodies, atomic-level structural information for viral surface proteins, and capacity for precision engineering of protein immunogens and self-assembling nanoparticles, a new era of antigen design and display options has evolved. While HIV-1 vaccine development has been a driving force behind these technologies and concepts, clinical proof-of-concept for structure-based vaccine design may first be achieved for respiratory syncytial virus (RSV), where conformation-dependent access to neutralization-sensitive epitopes on the fusion glycoprotein determines the capacity to induce potent neutralizing activity...
January 27, 2019: Annual Review of Medicine
https://read.qxmd.com/read/30379596/new-hope-for-therapeutic-cancer-vaccines-in-the-era-of-immune-checkpoint-modulation
#15
Michael A Curran, Bonnie S Glisson
The driver and passenger mutations accumulated in the process of malignant transformation offer an adequate spectrum of immune visible alterations to the cellular proteome and resulting peptidome to render these cancers targetable-and, in theory, rejectable-by the host T cell immune response. In addition, cancers often overexpress tissue-specific and developmental antigens to which immune tolerance is incomplete. Sometimes, virally transferred oncogenes drive malignant transformation and remain expressed throughout the cancer...
January 27, 2019: Annual Review of Medicine
https://read.qxmd.com/read/30365357/metformin-for-treatment-of-fragile-x-syndrome-and-other-neurological-disorders
#16
Ilse Gantois, Jelena Popic, Arkady Khoutorsky, Nahum Sonenberg
Fragile X syndrome (FXS) is the most frequent inherited form of intellectual disability and autism spectrum disorder. Loss of the fragile X mental retardation protein, FMRP, engenders molecular, behavioral, and cognitive deficits in FXS patients. Experiments using different animal models advanced our knowledge of the pathophysiology of FXS and led to the discovery of many targets for drug treatments. In this review, we discuss the potential of metformin, an antidiabetic drug approved by the US Food and Drug Administration, to correct core symptoms of FXS and other neurological disorders in humans...
January 27, 2019: Annual Review of Medicine
https://read.qxmd.com/read/30355266/long-acting-hiv-drugs-for-treatment-and-prevention
#17
Roy M Gulick, Charles Flexner
Antiretroviral drugs have revolutionized the treatment and prevention of HIV infection; however, adherence is critical for sustained efficacy. Current HIV treatment consists of three-drug regimens, and current HIV pre-exposure prophylaxis (PrEP) consists of a two-drug regimen; both generally require adherence to once-daily dosing. Long-acting formulations are useful in the treatment and prevention of other conditions (e.g., contraceptives, antipsychotics) and help promote adherence. Newer long-acting formulations of approved and investigational antiretroviral drugs in existing and newer mechanistic classes are under study for HIV treatment and prevention, including some phase III trials...
January 27, 2019: Annual Review of Medicine
https://read.qxmd.com/read/30355264/pd-1-blockade-in-early-stage-lung-cancer
#18
Samuel Rosner, Joshua E Reuss, Patrick M Forde
Early-stage non-small cell lung cancer is a potentially curable disease, but with relapse rates exceeding 50% with standard treatments, this is a patient population in critical need of therapy innovation. Immunotherapy with immune checkpoint blockade has revolutionized the treatment strategy for advanced lung cancer. However, the role of this therapy in earlier-stage disease is largely unknown. The study of immunotherapy in earlier-stage disease has many advantages, including assessment of pathologic response and incorporation of translational scientific analyses to evaluate antitumor immune responses...
January 27, 2019: Annual Review of Medicine
https://read.qxmd.com/read/30403551/the-global-landscape-of-tuberculosis-therapeutics
#19
Jeffrey A Tornheim, Kelly E Dooley
Tuberculosis (TB) is one of the oldest infections afflicting humans yet remains the number one infectious disease killer worldwide. Despite decades of experience treating this disease, TB regimens require months of multidrug therapy, even for latent infections. There have been important recent advances in treatment options across the spectrum of TB, from latent infection to extensively drug-resistant (XDR) TB disease. In addition, new, potent drugs are emerging out of the development pipeline and are being tested in novel regimens in multiple currently enrolling trials...
November 7, 2018: Annual Review of Medicine
https://read.qxmd.com/read/30403550/clinical-application-and-potential-of-fecal-microbiota-transplantation
#20
R E Ooijevaar, E M Terveer, H W Verspaget, E J Kuijper, J J Keller
Fecal microbiota transplantation (FMT) is a well-established treatment for recurrent Clostridioides difficile infection. FMT has become a more readily available and useful new treatment option as a result of stool banks. The current state of knowledge indicates that dysbiosis of the gut microbiota is implicated in several disorders in addition to C. difficile. Randomized controlled studies have shown FMT to be somewhat effective in treating ulcerative colitis, irritable bowel syndrome, and hepatic encephalopathy...
November 7, 2018: Annual Review of Medicine
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