Urothelial carcinoma in situ with "early papillary formation" vs "lateral spread/shoulder lesion" of prior high-grade noninvasive papillary urothelial carcinoma: A survey of pathologist and urologist interpretations.

Objectives: Urothelial carcinoma in situ (CIS) with early papillary formation is terminology sometimes used to suggest incipient high-grade papillary urothelial carcinoma (PUC) but may lead to confusion between true CIS and lateral flat spread of PUC.

Methods: It remains unclear how pathologists and urologists interpret this scenario, so a survey was circulated to 68 pathologists (group 1 = 28 academic genitourinary pathologists; group 2 = 17 pathologists with a self-reported genitourinary focus; group 3 = 23 pathologists self-reported as not genitourinary specialists) and 32 urologists.

Results: Regarding atypical urothelial lesions that appear mainly flat but contain possible papillae, group 3 was more likely to label this as CIS compared with groups 1 and 2 (35% for group 3 vs 13% for groups 1 and 2), while groups 1 and 2 more often adopted another descriptive diagnosis, such as "CIS with early papillary features" (38% for groups 1 and 2 vs 13% for group 3).

Long-term Changes in Pain, Depression, Function and Informal Caregiving after Major Elective Surgeries Among Seriously Ill Older Adults.

Objective: To compare differences in pain, depression, function, and informal caregiving pre-and-post major elective surgery among older adults with and without serious illness; and determine if serious illness was independently associated with increasing pain, depression, assistance in activities of daily living (ADLs) and informal caregiving post-surgery.

Background: The American College of Surgeons has endorsed the integration of palliative care (PC) into surgical care in adults with serious illness but targets for PC during surgical episodes such as pain, depression, function, and informal caregiving are understudied.

Methods: We used Health and Retirement Study-linked Medicare data (2008-2018) to identify older (≥66 y) adults with and without serious illness who had major elective surgery.

FBG-driven simulation for virtual augmentation of fluoroscopic images during endovascular interventions.

Endovascular interventions are procedures designed to diagnose and treat vascular diseases, using catheters to navigate inside arteries and veins. Thanks to their minimal invasiveness, they offer many benefits, such as reduced pain and hospital stays, but also present many challenges for clinicians, as they require specialized training and heavy use of X-rays. This is particularly relevant when accessing (i.

Long-Term Cognitive Safety of Achieving Very Low LDL Cholesterol with Evolocumab.

Background: Concerns persist regarding the cognitive safety of achieving very low levels of low-density lipoprotein (LDL) cholesterol. Although short-term studies are reassuring, the long-term cognitive effects of sustained exposure to very low LDL cholesterol levels through combined proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibition and statin therapy remain unknown.

Methods: This prospective study enrolled a subset of adults with atherosclerotic cardiovascular disease who had completed a neurocognitive substudy (EBBINGHAUS) of a placebo-controlled randomized trial of evolocumab (FOURIER) and were eligible for a long-term open-label extension.

Fine particulate matter and nonaccidental and cause-specific mortality: Do associations vary by exposure assessment method?

Background: There is considerable heterogeneity in fine particulate matter (PM)-mortality associations between studies, potentially due to differences in exposure assessment methods. Our aim was to evaluate associations of PM predicted from different models with nonaccidental and cause-specific mortality.

Methods: We followed 107,906 participants of the Nurses' Health Study cohort from 2001 to 2016.

Upper airway collapsibility during rapid eye movement sleep tracks the response to upper airway surgery for obstructive sleep apnea.

Objectives: Endotype-based intervention has shown promise in treatment for patients with obstructive sleep apnea, and upper airway surgery is an important therapeutic option. However, the response to surgery varies among patients with obstructive sleep apnea. This study aims to examine changes in endotypic traits following upper airway surgery and their association with surgical outcome.

The Alzheimer's Association clinical practice guideline for the Diagnostic Evaluation, Testing, Counseling, and Disclosure of Suspected Alzheimer's Disease and Related Disorders (DETeCD-ADRD): Executive summary of recommendations for specialty care.

US clinical practice guidelines for the diagnostic evaluation of cognitive impairment due to Alzheimer's disease (AD) or a related dementia (ADRD) are two decades old. This evidence-based guideline was developed to empower all clinicians to implement a structured approach for evaluating a patient with symptoms that may represent clinical AD/ADRD. An expert workgroup conducted a review of 7374 publications (133 met inclusion criteria) and developed recommendations as steps in an evaluation process.

Alzheimer's Association clinical practice guideline for the Diagnostic Evaluation, Testing, Counseling, and Disclosure of Suspected Alzheimer's Disease and Related Disorders (DETeCD-ADRD): Executive summary of recommendations for primary care.

US clinical practice guidelines for the diagnostic evaluation of cognitive impairment due to Alzheimer's disease (AD) or AD and related dementias (ADRD) are decades old and aimed at specialists. This evidence-based guideline was developed to empower all-including primary care-clinicians to implement a structured approach for evaluating a patient with symptoms that may represent clinical AD/ADRD. Through a modified-Delphi approach and guideline-development process (7374 publications were reviewed; 133 met inclusion criteria) an expert workgroup developed recommendations as steps in a patient-centered evaluation process.

The Alzheimer's Association clinical practice guideline for the diagnostic evaluation, testing, counseling, and disclosure of suspected Alzheimer's disease and related disorders (DETeCD-ADRD): Validated clinical assessment instruments.

US clinical practice guidelines for the diagnostic evaluation of cognitive impairment due to Alzheimer's Disease (AD) or AD and related dementias (ADRD) are decades old and aimed at specialists. This evidence-based guideline was developed to empower all-including primary care-clinicians to implement a structured approach for evaluating a patient with symptoms that may represent clinical AD/ADRD. As part of the modified Delphi approach and guideline development process (7374 publications were reviewed; 133 met inclusion criteria) an expert workgroup developed recommendations as steps in a patient-centered evaluation process.

Progress and Gaps in Respiratory Disease Research and Treatment: Highlights of the IRM 2024 in Shanghai.

Respiratory diseases pose a major public health challenge globally, necessitating collaborative efforts between basic researchers and clinicians for effective solutions. China, which is heavily impacted by a broad spectrum of respiratory disorders, has made notable strides in both research and clinical management of these diseases. The International Respiratory Medicine (IRM) meeting was organized with the primary goal of facilitating the exchange of recent research developments and promoting collaboration between Chinese and American scientists in both basic and clinical research fields.

AI-assisted human clinical reasoning in the ICU: beyond "to err is human".

Diagnostic errors pose a significant public health challenge, affecting nearly 800,000 Americans annually, with even higher rates globally. In the ICU, these errors are particularly prevalent, leading to substantial morbidity and mortality. The clinical reasoning process aims to reduce diagnostic uncertainty and establish a plausible differential diagnosis but is often hindered by cognitive load, patient complexity, and clinician burnout.

Severe pulmonary hypertension in chronic obstructive pulmonary disease - From clinical perspective to histological evidence.

Severe pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) is currently defined by an elevated mean pulmonary arterial pressure and strongly elevated pulmonary vascular resistance >5 wood units. Clinically, these patients show a male predominance, and usually present with very severe dyspnea, severe hypoxemia, strongly decreased exercise capacity and poor prognosis, even though the clinical picture is frequently associated with less severe airflow obstruction. Explanted lung samples of patients with COPD and severe PH show severe remodeling of small pulmonary arterioles, predominantly in the intima and media of the vessels.

InTraSeq: A Multimodal Assay that Uncovers New Single-Cell Biology and Regulatory Mechanisms.

Single-cell RNA sequencing (scRNA-seq) has revolutionized cell biology by enabling the profiling of transcriptomes at a single-cell resolution, leading to important discoveries that have advanced our understanding of cellular and tissue heterogeneity, developmental trajectories, and disease progression. Despite these important advances, scRNA-seq is limited to measuring the transcriptome providing a partial view of cellular function. To address this limitation, multimodal scRNA-seq assays have emerged, allowing for the simultaneous measurement of RNA expression and protein.

Siesta behavior and genetics interact to influence obesity risk.

Objective: In this cross-sectional study, we aim to investigate the interactions between obesity, siesta behavior, and the genetic propensity for siesta in a Mediterranean population, in whom siesta is deeply rooted.

Methods: We applied a previously generated Siesta-Polygenic Score (PGS) in the ONTIME study (n = 1278). Siesta and other Mediterranean lifestyle behaviors were characterized using questionnaires.

Physician-Patient Communication about Novel Drugs and High-Risk Medical Devices.

Background: After a new drug or medical device is approved by the US Food and Drug Administration (FDA), physician-patient communication about benefits and risks is critical, including whether the product was approved through an expedited pathway based on limited evidence. In addition, physician reporting of drug- and device-related adverse events in real-world use is necessary to have a complete safety profile. We studied physician-reported communication and safety-reporting practices related to drugs and devices.

RNA sensing induced by chromosome missegregation augments anti-tumor immunity.

Viral mimicry driven by endogenous double-stranded RNA (dsRNA) stimulates innate and adaptive immune responses. However, the mechanisms that regulate dsRNA-forming transcripts during cancer therapy remain unclear. Here, we demonstrate that dsRNA is significantly accumulated in cancer cells following pharmacologic induction of micronuclei, stimulating mitochondrial antiviral signaling (MAVS)-mediated dsRNA sensing in conjunction with the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway.

Bridging silicon and carbon worlds with digital twins and on-chip systems in drug discovery.

This perspective discusses the convergence of digital twin (DT) technology and on-the-chip systems as pivotal innovations in precision medicine, substantially advancing drug discovery. DT leverages extensive health data to create dynamic virtual patient models, enabling predictive insights and optimized treatment strategies. Concurrently, on-the-chip systems from the Carbon world replicate human biological processes on microfluidic platforms, providing detailed insights into disease mechanisms and pharmacological interactions.

Effectiveness of Virtual Care Team Guided Management of Hospitalized Patients with HFrEF by Ethnicity.

Background: IMPLEMENT-HF demonstrated a virtual team-based care strategy was safe and improved prescription of guideline directed medical therapy (GDMT) in hospitalized patients with heart failure and reduced ejection fraction (HFrEF). We evaluated differences in efficacy and safety outcomes by ethnicity in IMPLEMENT-HF.

Methods: IMPLEMENT-HF evaluated a provider-facing virtual team-based care strategy vs.

Readmission outcomes after acute coronary syndrome among patients with myeloproliferative neoplasms.

Background And Aims: Myeloproliferative neoplasms (MPNs) are associated with arterial thrombosis, including acute coronary syndrome (ACS). Prior studies have suggested similar in-hospital mortality among patients with MPN compared to those without. However, post-ACS outcomes have not been thoroughly evaluated.

The need for a cancer exposome atlas: a scoping review.

Background: Despite advances in understanding genetic susceptibility to cancer, much of cancer heritability remains unidentified. At the same time, the makeup of industrial chemicals in our environment only grows more complex. This gap in knowledge on cancer risk has prompted calls to expand cancer research to the comprehensive, discovery-based study of nongenetic environmental influences, conceptualized as the "exposome.

Greater baseline cortical atrophy in the dorsal attention network predicts faster clinical decline in Posterior Cortical Atrophy.

Background: Posterior Cortical Atrophy (PCA) is a clinical syndrome characterized by progressive visuospatial and visuoperceptual impairment. As the neurodegenerative disease progresses, patients lose independent functioning due to the worsening of initial symptoms and development of symptoms in other cognitive domains. The timeline of clinical progression is variable across patients, and the field currently lacks robust methods for prognostication.

Sphingolipid profiling as a biomarker of type 2 diabetes risk: evidence from the MIDUS and PREDIMED studies.

Background: Type 2 diabetes (T2D) has become a worldwide pandemic. While ceramides may serve as intermediary between obesity-related lipotoxicity and T2D, the relationship with simple glycosphingolipids remains uncertain. The aim of this study was to characterize the associations between blood glycosphingolipid and ceramide species with T2D and to identify a circulating sphingolipid profile that could serve as novel biomarker for T2D risk.

Longitudinal Assessment of Pain in Rheumatoid Arthritis: Increases in Pain and Their Relationship to Functional Declines and Medication Changes.

Objective: Electronic health applications (apps) allow patients with rheumatoid arthritis (RA) to report patient-reported outcomes (PROs) between visits. However, almost no data exist on patients' report of pain between visits and how that correlates with change in function and/or modifications to medication.

Methods: Patients with RA from one rheumatology practice provided data as part of a study of an app.