Secukinumab efficacy in patients with hidradenitis suppurativa assessed by the International Hidradenitis Suppurativa Severity Score System (IHS4): A post hoc analysis of the SUNSHINE and SUNRISE trials.

Introduction: The International Hidradenitis Suppurativa Severity Score System (IHS4) is a validated tool that measures inflammatory lesions, including draining tunnels, in hidradenitis suppurativa (HS).

Objective: To evaluate secukinumab efficacy using IHS4 in patients with moderate to severe HS.

Methods: Data from the SUNSHINE and SUNRISE trials, which assessed subcutaneous secukinumab 300 mg every 2 (SECQ2W) and 4 (SECQ4W) weeks in adults with moderate to severe HS, were analyzed.

Reach, engagement and effectiveness of in-person and online lifestyle change programs to prevent diabetes.

Background: COVID-19 has accelerated interest in and need for online delivery of healthcare. We examined the reach, engagement and effectiveness of online delivery of lifestyle change programs (LCP) modelled after the Diabetes Prevention Program (DPP) in a multistate, real-world setting.

Methods: Longitudinal, non-randomized study comparing online and in-person LCP in a large multistate sample delivered over 1 year.

Clinical Characteristics and Outcomes of Eyes with Intraocular Inflammation after Brolucizumab: Post Hoc Analysis of HAWK and HARRIER.

Purpose: This analysis of the pivotal phase 3 HAWK and HARRIER trials aimed to provide insights on the timing of presentation, management, and outcomes of intraocular inflammation (IOI)-related adverse events (AEs), as reported by investigators in these trials.

Design: Post hoc analysis of investigator-reported IOI-related AEs in HAWK and HARRIER.

Participants: Of 1088 brolucizumab-treated eyes (3 or 6 mg), 49 eyes demonstrated at least 1 IOI-related AE and were included in this analysis.

Post-lumpectomy breast calcifications: Can original tumor features assist in determining need for biopsy?

Objective: The objective of our study was to determine whether, in the digital era, imaging features of a primary breast tumor can be used to influence the decision to biopsy ipsilateral breast calcifications that occur following surgery in women treated with breast conservation surgery (BCS).

Materials And Methods: We retrospectively identified women treated with BCS who subsequently developed suspicious calcifications in the treated breast (BI-RADS 4 or 5) from January 2012 - December 2018. Only cases with histopathological diagnosis by stereotactic or surgical biopsy were included.

Diagnostic Accuracy of Amyloid versus F-Fluorodeoxyglucose Positron Emission Tomography in Autopsy-Confirmed Dementia.

Objective: The purpose of this study was to compare the diagnostic accuracy of antemortem C-Pittsburgh compound B (PIB) and F-fluorodeoxyglucose (FDG) positron emission tomography (PET) versus autopsy diagnosis in a heterogenous sample of patients.

Methods: One hundred one participants underwent PIB and FDG PET during life and neuropathological assessment. PET scans were visually interpreted by 3 raters blinded to clinical information.

A systematic review and meta-analysis examining the effects of cannabis and its derivatives in adults with malignant CNS tumors.

Background: Primary CNS tumors constitute a heterogeneous group of neoplasms that share a considerable morbidity and mortality rate. To help control tumor growth and clinical outcomes (overall survival, progression-free survival, quality of life) symptoms, patients often resort to alternative therapies, including the use of cannabis. Despite rapidly growing popularity, cannabis and its impact on patients with primary malignant CNS tumors is understudied.

Performance of screening MRI in high risk patients at initial versus subsequent screen.

Purpose: To compare the characteristics, outcomes, and performance metrics in women undergoing initial breast MRI screening versus subsequent screening.

Methods: A retrospective database search identified screening MRIs performed at an academic practice from 2013 to 2015. MRIs were divided into two groups: (1) initial screens and (2) subsequent screens (interpreted with at least one prior MRI for comparison).

Factors Predicting Metastatic Disease in Ga-PSMA-11 PET-Positive Osseous Lesions in Prostate Cancer.

Bone is the most common site of distant metastatic spread in prostate adenocarcinoma. Prostate-specific membrane antigen (PSMA) uptake has been described in both benign and malignant bone lesions, which can lead to false-positive findings on Ga-PSMA-11 PET. The purpose of this study was to evaluate the diagnostic accuracy of Ga-PSMA-11 PET for osseous prostate cancer metastases and improve bone uptake interpretation using semiquantitative metrics.

Pathogenic DDX3X Mutations Impair RNA Metabolism and Neurogenesis during Fetal Cortical Development.

De novo germline mutations in the RNA helicase DDX3X account for 1%-3% of unexplained intellectual disability (ID) cases in females and are associated with autism, brain malformations, and epilepsy. Yet, the developmental and molecular mechanisms by which DDX3X mutations impair brain function are unknown. Here, we use human and mouse genetics and cell biological and biochemical approaches to elucidate mechanisms by which pathogenic DDX3X variants disrupt brain development.

Pericardial Fat Enhancement: New Computed Tomography Biomarker Influences the Relationship Between Pericardial Fat and Coronary Artery Disease.

Purpose: Studies have shown a modest association between pericardial fat volume (PFV) and coronary artery disease (CAD), potentially mediated by local inflammation. We aimed to investigate the association between a new biomarker of pericardial fat inflammation, named pericardial fat enhancement (PFE), and the severity of CAD on coronary computed tomography angiography (CCTA).

Materials And Methods: We evaluated 114 patients referred for CCTA from 2007 to 2011.

Hyperpolarized pH imaging reveals grade-dependent acidification in prostate cancer.

There is an unmet clinical need for new and robust imaging biomarkers to distinguish indolent from aggressive prostate cancer. Hallmarks of aggressive tumors such as a decrease in extracellular pH (pH) can potentially be used to identify aggressive phenotypes. In this study, we employ an optimized, high signal-to-noise ratio hyperpolarized (HP) C pH imaging method to discriminate between indolent and aggressive disease in a murine model of prostate cancer.

A Simple Approximation to Bias in Gene-Environment Interaction Estimates When a Case Might Not Be the Case.

Case-control genetic association studies are often used to examine the role of the genetic basis in complex diseases, such as cancer and neurodegenerative diseases. The role of the genetic basis might vary by nongenetic (environmental) measures, what is traditionally defined as gene-environment interactions (G×E). A commonly overlooked complication is that the set of clinically diagnosed cases might be contaminated by a subset with a pathologic state that presents with the same symptoms as the pathologic state of interest.

Case-control versus case-only estimates of gene-environment interactions with common and misclassified clinical diagnosis.

Genetic studies provide valuable information to assess if the effect of genetic variants varies by the nongenetic "environmental" variables, what is traditionally defined to be gene-environment interaction (GxE). A common complication is that multiple disease states present with the same set of symptoms, and hence share the clinical diagnosis. Because (a) disease states might have distinct genetic bases; and (b) frequencies of the disease states within the clinical diagnosis vary by the environmental variables, analyses of association with the clinical diagnosis as an outcome variable might result in false positive or false negative findings.

The impact of technical parameters on ablation volume during MR-guided focused ultrasound of desmoid tumors.

Purpose: Desmoid tumors are benign, locally aggressive soft tissue tumors derived from fibroblasts. Magnetic resonance-guided focused ultrasound (MRgFUS) is a safe and effective treatment for desmoid tumors. The purpose of this study was to retrospectively review the MRgFUS treatments of desmoid tumors at our institution to determine which technical treatment parameters contributed most significantly to the accumulation of thermal dose.

A simple approximation to bias in the genetic effect estimates when multiple disease states share a clinical diagnosis.

Case-control genome-wide association studies (CC-GWAS) might provide valuable clues to the underlying pathophysiologic mechanisms of complex diseases, such as neurodegenerative disease and cancer. A commonly overlooked complication is that multiple distinct disease states might present with the same set of symptoms and hence share a clinical diagnosis. These disease states can only be distinguished based on a biomarker evaluation that might not be feasible in the whole set of cases in the large number of samples that are typically needed for CC-GWAS.

A simple approximation to the bias of gene-environment interactions in case-control studies with silent disease.

One of the most important research areas in case-control Genome-Wide Association Studies is to determine how the effect of a genotype varies across the environment or to measure the gene-environment interaction (G × E). We consider the scenario when some of the "healthy" controls actually have the disease and when the frequency of these latent cases varies by the environmental variable of interest. In this scenario, performing logistic regression with the clinically diagnosed disease status as an outcome variable and will result in biased estimates of G × E interaction.

Female XX sex chromosomes increase survival and extend lifespan in aging mice.

Female longevity is observed in humans and much of the animal kingdom, but its causes remain elusive. Using a genetic manipulation that generates XX and XY mice, each with either ovaries or testes, we show that the female XX sex chromosome complement increases survival during aging in male and female mice. In combination with ovaries, it also extends lifespan.

Bias in parameter estimates due to omitting gene-environment interaction terms in case-control studies.

Genetic studies are continuing to generate volumes and variety of data that can be used to examine the genetic effects. Often the effect of a genetic variant varies by nongenetic measures, what is traditionally defined as gene-environment interaction (G×E). If the G×E term is neglected, estimates of the main effects can be substantially biased.

Microcalcifications Detected at Screening Mammography: Synthetic Mammography and Digital Breast Tomosynthesis versus Digital Mammography.

Purpose To compare the performance of two-dimensional synthetic mammography (SM) plus digital breast tomosynthesis (DBT) versus conventional full-field digital mammography (FFDM) in the detection of microcalcifications on screening mammograms. Materials and Methods In this retrospective multireader observer study, 72 consecutive screening mammograms recalled for microcalcifications from June 2015 through August 2016 were evaluated with both FFDM and DBT. The data set included 54 mammograms with benign microcalcifications and 18 mammograms with malignant microcalcifications, and 20 additional screening mammograms without microcalcifications used as controls.

Case-control studies of gene-environment interactions. When a case might not be the case.

Case-control Genome-Wide Association Studies (GWAS) provide a rich resource for studying the genetic architecture of complex diseases. A key is to elucidate how the genetic effects vary by the environment, what is traditionally defined by Gene-Environment interactions (GxE). The overlooked complication is that multiple, distinct pathophysiologic mechanisms may lead to the same clinical diagnosis and often these mechanisms have distinct genetic bases.

Gene-environment interactions in case-control studies with silent disease.

Genome-wide association studies (GWAS) often measure gene-environment interactions (G × E). We consider the problem of accurately estimating a G × E in a case-control GWAS when a subset of the controls have silent, or undiagnosed, disease and the frequency of the silent disease varies by the environmental variable. We show that using case-control status without accounting for misdiagnosis can lead to biased estimates of the G × E.