Landmark Trials

BACKGROUND: Circulating tumour DNA (ctDNA)-based molecular residual disease (MRD) detection technology has been widely used for recurrence evaluation, but there is no agreement on the efficacy of assessing recurrence and overall survival (OS) prognosis, as well as the sensitivity and specificity of landmark detection and longitudinal detection. METHODS: We systematically searched Pubmed, Embase, Cochrane, and Scopus for prospective studies or randomized controlled trials that collected blood samples prospectively...

Gastroesophageal adenocarcinoma (GEA) is one of the principal causes of death related to cancer globally. Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase receptor which is found to be overexpressed or amplified in approximately 20% of GEA cases. In GEA, the identification of HER2-positive status is crucial to activate a specific anti-HER2 targeted therapy. The landmark ToGA trial demonstrated the superiority of adding trastuzumab to platinum-based chemotherapy, becoming the first-line standard of treatment...

Diabetes mellitus (DM) is a chronic metabolic disease affecting over 500 million people worldwide, which leads to severe complications and to millions of deaths yearly. When therapeutic goals are not reached with diet, physical activity, or non-insulin drugs, starting/adding insulin treatment is recommended by international guidelines. A novel recombinant insulin is icodec, a once-weekly insulin that successfully completed phase III trials and that has recently obtained the marketing authorization approval from the European Medicines Agency...

Background: Cardiac resynchronization therapy (CRT) has evolved into an established therapy for patients with chronic heart failure and a wide QRS complex. Data on long-term outcomes over time are scarce and the criteria for implantation remain a subject of investigation. Methods: An international, multicenter, retrospective registry includes 2275 patients who received CRT between 30 November 2000 and 31 December 2019, with a mean follow-up of 3.6 ± 2.7 years. Four time periods were defined, based on landmark trials and guidelines...

Here, we present a protocol to quantify bird nest morphology via image analyses. We describe steps for collecting linear size measurements, placing geometric landmarks, and undertaking generalized Procrustes analysis to extract coordinate data. This protocol was designed to measure within- and among-individual variation in the morphology of dome nests built by captive zebra finches using coconut fiber in a laboratory environment. For complete details on the use and execution of this protocol, please refer to Whittaker et al...

INTRODUCTION: Heart failure patients with a history of atrial fibrillation (AF) and ventricular tachycardia/ventricular fibrillation (VT/VF) are known to have worse outcomes. However, there are limited data on the temporal relationship between development of these arrhythmias and the risk of subsequent congestive heart failure (CHF) exacerbation and death. METHODS: The study cohort comprised 5511 patients implanted with an implantable cardioverter-defibrillator (ICD) in landmark clinical trials (MADIT-II, MADIT-RISK, MADIT-CRT, MADIT-RIT, and RAID) who were in sinus rhythm at enrollment...

AIM: There have been a number of clinical trials in glaucoma research published in the past two decades. Most of these trials were designed to evaluate very specific issues in selected populations placing them in the explanatory end of the pragmatic-explanatory continuum. The purpose of this study was to assess the level of pragmatism of published randomized controlled trials in glaucoma. METHODS: A PubMed search using 'glaucoma' from 1995 to 2022 and randomized controlled trial (RCT) article type was done...

Respiratory syncytial virus (RSV) is the leading cause of hospitalization in infancy in the United States. Nearly all infants are infected by 2 years of age, with bronchiolitis requiring hospitalization often occurring in previously healthy children and long-term consequences of severe disease including delayed speech development and asthma. Incomplete passage of maternal immunity and a high degree of genetic variability within the virus contribute to morbidity and have also prevented successful neonatal vaccine development...

While it is evident that standard dose whole brain radiotherapy as consolidation is associated with significant neurotoxicity, the optimal consolidative strategy for primary central nervous system lymphoma (PCNSL) is not defined. We performed a randomized phase 2 clinical trial via the U.S. Alliance cancer cooperative group to compare myeloablative consolidation supported by autologous stem cell transplantation with non-myeloablative consolidation after induction therapy for PCNSL. This is the first randomized trial to be initiated that eliminates whole brain radiotherapy as a consolidative approach in newly-diagnosed PCNSL...

The US Food and Drug Administration (FDA)'s authorization of etranacogene dezaparvovec (Hemgenix) is a significant milestone, constituting not only the first FDA approval of a gene therapy for hemophilia but also the first approval of a liver-targeted adeno-associated virus vector gene therapy. This review summarizes the nonclinical studies and clinical development that supported regulatory clearance. Similar to other gene therapies for single gene disorders, both the short-term safety and the phenotypic improvement were unequivocal, justifying the modest-sized safety and efficacy database, which included 57 participants across the phase 2b (3 participants) and phase 3 (54 participants) studies...

INTRODUCTION: Invisible ink tattoos (IITs) avoid cosmetic permanence of visible ink tattoos (VITs) while serving as more reliable landmarks for radiation setup than tattooless setups. This trial evaluated patient-reported preference and feasibility of IIT implementation. METHODS AND MATERIALS: In an IRB-approved, single institution, prospective trial, patients receiving proton therapy underwent IIT-based treatment setup. A survey tool assessed patient preference on tattoos using a Likert scale...

PURPOSE OF REVIEW: This manuscript will update prior reviews of immune checkpoint inhibitors (ICIs) in light of basic science, translational, and clinical discoveries in the field of cancer immunology and aging. RECENT FINDINGS: ICIs have led to significant advancements in the treatment of cancer. Landmark trials of ICIs have cited the efficacy and toxicity experienced by older patients, but most trials are not specifically designed to address outcomes in older patients...

BACKGROUND: There is limited literature guiding the prescribing of direct oral anticoagulants (DOACs) early after cardiac surgery as this population has been excluded from landmark randomized controlled trials. This study aims to determine the rate of in-hospital DOAC use compared with warfarin early after cardiac surgery, evaluate factors associated with DOAC use, determine difference in postoperative length of stay, and characterize bleeding events. METHODS: A retrospective cohort study was conducted in adult patients with indications for anticoagulation and receiving either a DOAC or warfarin after cardiac surgery during their index hospitalization...

BACKGROUND: Landmark clinical trials have expended the indications for the direct oral anticoagulants (DOACs), but contemporary data on usage and expenditure patterns are lacking. OBJECTIVE: This study aimed to assess annual trends in oral anticoagulant (OAC) utilization and expenditure across the United States (US) from 2014 to 2020. METHODS: We utilized the Medical Expenditure Panel Survey (MEPS) to study the trends of use and expenditures of warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban between 2014 and 2020 in the US...

Species of crab have been shown to spatially track and navigate to consequential. locations through different processes, such as path integration and landmark orienting. Few investigations examine their ability to wayfind in complex environments, like. mazes, with multiple intersections and how they may utilize specific features to benefit. this process. Spatial learning potentially would lend a fitness advantage to animals. living in complicated habitats, and ghost crab (Ocypode quadrata) is a semiterrestrial...

The rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) poses a significant global health challenge, affecting over 30% of adults worldwide. MASLD is linked to increased mortality rates and substantial healthcare costs, primarily driven by its progression to metabolic dysfunction-associated steatohepatitis (MASH), which can lead to severe liver complications including cirrhosis and hepatocellular carcinoma. Despite its growing burden, effective pharmacotherapy for MASLD/MASH has been lacking until the recent conditional approval of resmetirom by the FDA...

BACKGROUND: Ipilimumab disinhibits immune system activity which results in the elimination of malignant cells. An unintended consequence of ipilimumab therapy is off-target immune-related adverse events (irAEs). It has therefore been proposed that the incidence of irAEs is a manifestation of treatment effectiveness. The objective of this systematic review is to examine the relationship between irAEs and survivability among melanoma patients administered ipilimumab monotherapy. METHODS: A comprehensive search was conducted across several databases which yielded a total of 2381 studies...

Precise measurement of joint-level motion from stereo-radiography facilitates understanding of human movement. Conventional procedures for kinematic tracking require significant manual effort and are time intensive. The current work introduces a method for fully automatic tracking of native knee kinematics from stereo-radiography sequences. The framework consists of three computational steps. First, biplanar radiograph frames are annotated with segmentation maps and key points using a convolutional neural network...

BACKGROUND: Upper oesophageal sphincter (UES) serves as an important anatomical and functional landmark during swallowing. However, the precise UES location before and during swallowing has not been well established. OBJECTIVE: This study aimed to determine upper oesophageal sphincter (UES) location and displacement during swallowing accounting for sex, age, and height in healthy adults using 320-row area detector computed tomography (320-ADCT). METHODS: Ninety-four healthy adults (43 males; 22-90 years) underwent 320-ADCT scanning while swallowing one trial of 10 mL honey thick barium...

Kinematic tracking of native anatomy from stereo-radiography provides a quantitative basis for evaluating human movement. Conventional tracking procedures require significant manual effort and call for acquisition and annotation of subject-specific volumetric medical images. The current work introduces a framework for fully automatic tracking of native knee anatomy from dynamic stereo-radiography which forgoes reliance on volumetric scans. The method consists of three computational steps. First, captured radiographs are annotated with segmentation maps and anatomic landmarks using a convolutional neural network...