Citations

The Doppler twinkling artifact (TA) plays a crucial role in detecting some biopsy markers including those made of polymethyl methacrylate (PMMA), facilitating precise lymph node localization in diagnostic and therapeutic procedures. This study presents comprehensive signal processing analysis methods to quantify and characterize the TA phenomenon using raw, per-channel radiofrequency (RF) data acquired from PMMA markers scanned with an L7-4 linear array transducer. We evaluated signals at different stages along the image reconstruction pipeline including (1) beamforming, (2) beamformed RF signal conversion into in-phase/quadrature (IQ) signals, and (3) Doppler velocity calculations and image reconstruction. We analyzed changes of pulses within an ensemble and between ensembles (i.e., frames). We also evaluated the impact of wall filters with various cutoff frequencies on color and power Doppler image reconstruction. Comparative analysis between PMMA markers and a non-twinkling control sample demonstrated distinct TA signatures or lack thereof in color and power Doppler images. The IQ data from PMMA marker locations exhibiting TA signatures showed substantially higher variability compared to non-twinkling samples, with standard deviations approximately 20 times higher between ensembles and 5 times higher within ensembles. This quantitative analysis framework provides valuable insight into the TA signal, potentially leading to more reliable and accurate diagnostic interpretations.

The color Doppler twinkling artifact has been attributed to existing microbubbles or cavitation has been reported for objects with rough surfaces like kidney stones, sandpaper, and polymethyl methacrylate (PMMA) bone cement. Passive cavitation detection (PCD) is a method for determining the presence of bubble oscillation from subharmonic, ultraharmonic, and inharmonic components in the Fourier domain. We evaluated multiple PMMA samples with varying twinkling amounts as well as a non-twinkling metal rod. Ultrasound scans were conducted using a Verasonics L11-4v probe on a V1 system from 3–9 MHz Doppler transmit frequency. A Sonic Concepts Y-107 PCD probe connected to a JSR DPR300 pulser/receiver collected data during Doppler ultrasound transmission. The Fourier spectra showed increased magnitude trends in the midband frequency range between the fundamental, f, and second harmonic, 2f, on the twinkling samples compared to non-twinkling metal rod. The midband increase was highest at frequencies that showed the most twinkling. This work indicates that the presence of color Doppler twinkling signal on PMMA gives rise to additional peaks in the Fourier domain, particularly in the midband range. Additionally, as there were no distinct subharmonic peaks, the increased midband magnitudes could be due to cavitation on the rough surfaces of the PMMA.

Abstract Background and Aims Truncating variants in the TTN gene (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM) but also occur as incidental findings in the general population. This study investigated factors associated with the clinical manifestation of TTNtv. Methods An international multicentre retrospective observational study was performed in families with TTNtv-related DCM. Shared frailty models were used to estimate associations of variant characteristics with lifetime risk of DCM, and logistic regression to estimate odds ratios (ORs) for individual-level clinical risk factor profiles (cardiac conditions, cardiovascular comorbidities, lifestyle) and DCM. Results A total of 3158 subjects in 1043 families with TTNtv-related DCM were studied. TTNtv-positive subjects were 21-fold more likely to develop DCM [OR, 21.21; 95% confidence interval (CI), 14.80–30.39]. Disease onset was earlier in males, but was similar for TTNtv of different types and locations. The presence of clinical risk factors was associated with earlier DCM onset (OR, 3.41; 95% CI, 2.06–5.64), with a prior history of atrial fibrillation having a two-fold increased odds of DCM (OR, 2.05; 95% CI, 1.27–3.32). The prevalence of clinical risk factors increased with age; however, the strength of the DCM association was greatest for young-onset (<30 years) disease (OR, 4.75; 95% CI, 2.35–9.60). Administration of beta-adrenergic receptor or renin-angiotensin system-blocking drugs prior to overt DCM was associated with 87% reduced odds of DCM (OR, .13; 95% CI, .08–.23). Conclusions Disease onset in TTNtv-associated familial DCM is dependent on individual patient context and is potentially modifiable by risk factor management and prophylactic therapeutic intervention.

ABSTRACTIntroductionProton beam therapy (PT) offers a targeted approach to treating pediatric tumors by minimizing radiation exposure to surrounding healthy tissue. However, the specific toxicity profile associated with it remains underexplored. This study aims to investigate the incidence and risk factors of acute and late treatment‐related toxicities following PT in pediatric patients with pelvic tumors.MethodsUsing data from the Pediatric Proton Consortium Registry (PPCR), we analyzed 126 pediatric patients who underwent PT for pelvic tumors. We assessed the incidence of gastrointestinal (GI), genitourinary (GU), and musculoskeletal (MSK) toxicities at baseline, during treatment, and across follow‐up intervals.ResultsAcute toxicities were observed in 61.9% of patients posttreatment, with new GI, GU, and MSK toxicities occurring in 54.3%, 9.7%, and 7.0% of baseline toxicity‐free patients, respectively. Follow‐up indicated that 20.6%, 22.2%, and 13.5% of patients developed late GI, GU, and MSK toxicities, respectively. Use of passive scattering proton therapy and radiation to the abdomen were significant predictors of GI toxicity development, while higher radiation dose was associated with MSK toxicity development.ConclusionOur findings demonstrate the safety profile of PT among pediatric patients while identifying specific risk factors, such as passive scattering proton therapy and abdominal irradiation, that contribute to increased GI toxicity. While proton therapy appears to be a well‐tolerated treatment option, the observed toxicity rates highlight the need for continued monitoring and long‐term follow‐up.

Abstract Endoscopic bariatric and metabolic therapies (EBMTs) are increasingly recognized as valuable tools for managing obesity and related metabolic disorders. As the prevalence of obesity continues to rise globally, there is a growing demand for effective, safe, and less invasive treatment options. This review provides a comprehensive summary of the available EBMTs, including both stomach-targeted and small-bowel-targeted devices. The review details the various devices, outlines the techniques for their proper use, and discusses their indications. It also presents data on their efficacy and safety, and the management of adverse events and weight regain, as well as anticipated future developments. The paper emphasizes the necessity for additional high quality randomized controlled trials and long-term outcome data to better define the role of these therapies within obesity treatment protocols. Overall, this review serves as an authoritative resource for endoscopists, bariatric specialists, and the wider healthcare community involved in obesity care, promoting best practices and guiding the appropriate implementation of EBMTs in clinical settings.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disorder. It is primarily caused by pathogenic variants in the PKD1 or PKD2 genes. This leads to the development of numerous kidney cysts, which can result in kidney enlargement and progression to kidney failure. Pain is a common symptom in ADPKD and can negatively affect quality of life (QOL). This pain is often due to the continuous growth of kidney and liver cysts or associated cystic complications. We present a case of a 29-year-old woman with ADPKD who experienced chronic, refractory right-sided flank pain that significantly affected her QOL. Her pain persisted despite taking daily multimodal analgesics and undergoing multiple invasive interventions. She had an unusual asymmetric disease with the right kidney accounting for only 24% of her kidney function. After exhausting all other pain control strategies, she underwent right nephrectomy and partial hepatectomy, which led to substantial improvement in pain and QOL. This review describes the causes, manifestations, and management strategies for abdominal and/or flank pain in ADPKD, including a practical stepwise algorithm to guide clinicians in managing pain and improve QOL of patients with ADPKD. Pain in ADPKD can either be acute or chronic and can lead to significant physical and psychologic distress. Effective pain management in ADPKD requires a multidisciplinary approach, incorporating both nonpharmacologic and pharmacologic interventions such as gabapentin or tolvaptan in select cases. Interventions considered in ADPKD pain control include cyst aspiration with sclerotherapy, celiac plexus blockade, spinal cord stimulation, renal denervation, or nephrectomy.

Pediatric metabolic dysfunction–associated steatotic liver disease (MASLD) has become more prevalent on a global scale over the last decades and is associated with significant comorbidities in childhood and a 40-fold higher risk of early mortality in young adulthood. MASLD has now become the leading indication for liver transplantation in young adults in the United States. However, pediatric MASLD is still perceived as an indolent condition by many patients, families, and clinicians. In this Call to Action, we aim to raise awareness of pediatric MASLD as a public health crisis. Herein, we describe insufficient screening and disease staging practices, and a lack of accurate non-invasive tests and effective pharmacotherapy, both stemming from a paucity of multicenter clinical trials in pediatric MASLD. We provide clear steps to address this public health emergency by promoting awareness campaigns, educating and empowering patients and families, addressing barriers including access to care, nutritional and exercise support programs, establishing multidisciplinary care, launching community initiatives, and conducting clinical trials in pediatric MASLD for an age-based evaluation of novel diagnostic and therapeutic options. We conclude by highlighting the urgent need for comprehensive public health policies to control the tide of pediatric MASLD and call upon stakeholders to act now.

Abstract Single‐molecule immunoassay is a reliable technique for the detection and quantification of low‐abundance blood biomarkers, which are essential for early disease diagnosis and biomedical research. However, current single‐molecule methods predominantly rely on endpoint detection and necessitate signal amplification via labeling, which brings a variety of unwanted effects, like matrix effect and autofluorescence interference. This study introduces a real‐time mass imaging‐based label‐free single‐molecule immunoassay (LFSMiA). Featuring plasmonic scattering microscopy‐based mass imaging, a 2‐step sandwich assay format enables background reduction, minimization of matrix effect by dynamic tracking of single binding events, and fully leveraging real‐time data for improved measurement precision through a Bayesian Gaussian process model, the LFSMiA enables ultra‐sensitive and direct protein detection at the single‐molecule level in neat blood sample matrices. LFSMiA measurement is demonstrated for interleukin‐6 and prostate‐specific antigen in buffer, undiluted serum, and whole blood with sub‐femtomolar detection limits and eight logs of dynamic ranges. Moreover, comparable performance is achieved with an inexpensive miniaturized setup. To show its translational potential to clinical settings and point‐of‐care diagnostics, N‐terminal pro‐B‐type natriuretic peptide is examined in patient whole blood samples using the LFSMiA and results in a strong linear correlation (r > 0.99) with standard clinical lab results.