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Breast Cancer Method of Detection: Frequently Asked Questions
Bahl, Manisha , Aminololama‐Shakeri, Shadi , Chen, L, Chikarmane, Sona A. , Dontchos, Brian N. , Lampen-Sachar, Katharine , Langman, Eun L. , Rosen, Eric L. , Rossi, Joanna , Ghate, Sujata V. , Dontchos, Brian N , Ojeda-Fournier, Haydee , Rossi, Joanna , Sharpe, Richard E. , Destounis, Stamatia V. , Eby, Peter R.

Journal of Breast Imaging | July 26, 2025 | Volume: 7 | Issue: 6 | Pages: 718-728

10.1093/jbi/wbaf048 | PMID 41183368 Get It

Abstract The initial method of detection (MOD) refers to the first imaging examination, physical symptom, or clinical sign that prompts further investigation and ultimately leads to a new breast cancer diagnosis. The MOD is assigned at the patient level and falls into 1 of 3 categories: screening in asymptomatic patients, detection by patients or health care providers, or neither of the above. The MOD should be assigned prospectively by the radiologist when interpreting an examination with a final BI-RADS category of 4 or 5, before image-guided biopsy and breast cancer diagnosis. The MOD is not assigned to examinations classified as BI-RADS category 0, 1, 2, 3, or 6, nor is it assigned in the setting of an active breast cancer diagnosis. This Clinical Practice article addresses frequently asked questions and challenging clinical scenarios compiled by the American College of Radiology’s Screening and Emerging Technology Committee to guide consistent MOD assignment. For example, if a patient presents with a lump but is ultimately found to have a suspicious finding requiring biopsy in the contralateral breast, the MOD should reflect the reason for presentation, the patient-detected symptom (Pat), even if the cancer itself is asymptomatic. By increasing awareness of MOD and standardizing MOD reporting practices, radiologists can contribute to improved data collection. While MOD is not currently tracked in U.S. cancer registries, its systematic collection may offer valuable insights into screening effectiveness, technology performance, and disparities in cancer detection. Standardized MOD reporting has the potential to strengthen early detection efforts and improve outcomes across diverse clinical settings.
Evaluation of Brain Stiffness in Patients Undergoing Carotid Angioplasty and Stenting Using Magnetic Resonance Elastography
Murphy, Matthew C. , Chen, Shu‐Ting , Lirng, Jiing‐Feng , Luo, Chao‐Bao , Rossman, Phillip J. , Ehman, Richard L. , Wu, Chia-Hung , Ehman, Richard , Chiang, Chia‐Chun , Chung, Chih‐Ping , Luo, Chao‐Bao , Huston, John , Chang, Feng‐Chi

Journal of Magnetic Resonance Imaging | July 24, 2025 | Volume: 62 | Issue: 5 | Pages: 1371-1380

10.1002/jmri.70049 | PMID 40702965 Get It

ABSTRACTBackgroundPercutaneous transluminal angioplasty and stenting (PTAS) in patients with carotid stenosis may have potential effects on brain parenchyma. However, current studies on parenchymal changes are scarce due to the need for advanced imaging modalities. Consequently, the alterations in brain parenchyma following PTAS remain an unsolved issue.PurposeTo investigate changes to the brain parenchyma using magnetic resonance elastography (MRE).Study TypeProspective.Population13 patients (6 women and 7 men; 39 MRI imaging sessions) with severe unilateral carotid stenosis patients indicated for PTAS were recruited between 2021 and 2024.Field Strength/SequenceNoncontrast MRI sequences including MRE (spin echo) were acquired using 3 T scanners.AssessmentAll patients underwent MRE before (preprocedural), within 24 h (early postprocedural) and 3 months after (delayed postprocedural) PTAS. Preprocedural and delayed postprocedural ultrasonographic peak systolic velocity (PSV) was recorded. MRE stiffness and damping ratio were evaluated via neural network inversion of the whole brain, in 14 gray matter (GM) and 12 white matter (WM) regions.Statistical TestsStiffness and damping ratio differences between each pair of MR sessions for each subject were identified by paired sample t tests. The correlations of stiffness and damping ratio with stenosis grade and ultrasonographic PSV dynamics were evaluated by Pearson correlation coefficients. The statistical significance was defined as p < 0.05.ResultsThe stiffness of lesion side insula, deep GM, and deep WM increased significantly from preprocedural to delayed postprocedural MRE. Increasing deep GM stiffness on the lesion side was positively correlated with the DSA stenosis grade significantly (r = 0.609). The lesion side insula stiffness increments were positively correlated with PSV decrements significantly (r = 0.664).Data ConclusionRegional brain stiffness increased 3 months after PTAS. Lesion side stiffness was positively correlated with stenosis grades in deep GM and PSV decrements in the insula.Evidence Level2.Technical EfficacyStage 2.
Twice‐daily administration improves the effectiveness of 0.01% atropine for controlling myopia in slowing axial elongation and refractive progression
Xu, Shengsong , Wang, M Y , Qu, Yan , Jiang, Jinyun , Zhao, Wenchen , Zheng, Bingru , Lei, Xingyu, Li, Zhouyue , Hu, Yin , Wang, Mengyi , Zhou, Fengqi, Zheng, Bingru , Yang, Xiao , Qu, Yiwen, Wang, Yanbin , Zhou, Fengqi , Chen, Weiyin, Lei, Xingyu

Ophthalmic and Physiological Optics | July 23, 2025 | Volume: 45 | Issue: 7 | Pages: 1856-1866

10.1111/opo.13558 | PMID 40698880 Get It

Abstract Purpose It remains unclear whether increasing the frequency of administration of 0.01% atropine improves its effectiveness in slowing axial elongation or refractive progression. This study compared twice‐daily 0.01% atropine administration and traditional once‐nightly administration. Methods A hybrid design was adopted incorporating both retrospective and prospective elements, with participants observed for 1 year. The control group (received saline eye drops) and once‐daily 0.01% atropine group (Atropine‐1 group) were derived from two previous trials, while the twice‐daily 0.01% atropine group (Atropine‐2 group) was enrolled prospectively. A total of 163 participants were included in the intention‐to‐treat set, with 51, 70 and 42 participants in the control, Atropine‐1 and Atropine‐2 groups, respectively. The primary outcome was the change in axial length (AL), and the secondary outcome was the change in cycloplegic spherical equivalent refraction (SER). Results Compared with the control group (0.48 ± 0.22 mm), both Atropine‐1 (0.26 ± 0.17 mm) and Atropine‐2 (0.15 ± 0.18 mm) groups showed significantly reduced AL elongation ( p < 0.001). Notably, Atropine‐2 significantly improved slowing of AL elongation compared with Atropine‐1 ( p = 0.008). The result of the secondary outcome (adjusted SER change) was consistent. Atropine‐2 was significantly more effective in slowing SER progression (−0.15 ± 0.37 D) than Atropine‐1 (−0.41 ± 0.50 D) ( p = 0.02). Based on a multivariable model, age was identified as the key covariate to perform subgroup analyses. In the younger subgroup (8–10 years), AL elongation was significantly reduced in the Atropine‐2 group (0.16 ± 0.17 mm) compared with the Atropine‐1 group (0.36 ± 0.22 mm; p = 0.002). In the older subgroup (10–12 years), there was no significant difference in progression. Consistent results were observed in the sensitivity analyses based on the per‐protocol set. Conclusion Twice‐daily administration of 0.01% atropine was more effective than once daily in slowing AL elongation and SER progression in children 8 to 10 years of age. Further investigation with extended follow‐up is warranted to substantiate this finding.
Restoration of SIRT3 Expression in Aged Mice Alleviates UUO‐Induced Renal Fibrosis by Reducing GSK‐3β Hyperacetylation
Lu, Huan , Guo, Zihao , Li, Xing , Tian, Yiqun, Yin, Yisheng , Qin, Zhenliang, Yun, Kun , Wu, Minglong, Zeng, Xiaoyong , Zeng, Xiaoyong , Wang, Jing , Ren, Xiang , Yun, Kun, Chen, Gang

Advanced Science | July 23, 2025 | Volume: 12 | Issue: 39 | Pages: No page available

10.1002/advs.202417248 | PMID 40698425 Get It

Abstract Aging increases the vulnerability of kidneys to injury and impairs their regenerative capacity. SIRT3 expression declines with aging and is associated with multiple age‐related pathologies. The expression profile and functional role of SIRT3 in renal aging remain unclear. Here, SIRT3 expression in aging kidneys is assessed and analyzed for its promoter methylation patterns using methylation‐specific PCR (MSP). It is found that aging exacerbates UUO‐induced renal fibrosis, associated with downregulated SIRT3 expression. Mechanistically, age‐related SIRT3 downregulation is mediated by hypermethylation of its promoter region. SIRT3 knockout exacerbated renal fibrosis in young mice subjected to UUO, whereas SIRT3 overexpression attenuated fibrosis in aged UUO mice. Integration of RNA‐seq and immunoprecipitation‐mass spectrometry (IP‐MS) analyses revealed that SIRT3 deficiency leads to hyperacetylation of GSK3β at lysine 15 (K15). This K15 hyperacetylation inhibited GSK3β activity, consequently stabilizing its substrate β‐catenin. Furthermore, self‐assembled PEG‐PCL‐PEG micelles are designed and synthesized to encapsulate hydrophobic honokiol (HKL). These micelles significantly enhanced the aqueous solubility and oral bioavailability of free HKL, maintained stable blood concentrations, and ultimately improved its anti‐fibrotic efficacy. These findings propose novel therapeutic strategies for managing renal fibrosis in the aging population and provide a foundation for developing new drugs and combination therapies.
MRI characteristics during attack and remission distinguish patients with MOG antibody-associated disease from multiple sclerosis
Cacciaguerra, Laura , Tajfirouz, Deena , Redenbaugh, Vyanka , Krecke, Karl N. , Thakolwiboon, Smathorn , Madhavan, Ajay A. , Tillema, Jan-Mendelt , López‐Chiriboga, A. Sebastian , Chen, John J. , Syc-Mazurek, Stephanie B , Cacciaguerra, Laura , Tajfirouz, Deena , Thakolwiboon, Smathorn , Madhavan, Ajay A , Valencia Sanchez, Cristina , Sechi, Elia , Pittock, S J , Flanagan, E P , Chen, John J , Syc‐Mazurek, Stephanie B. , Dinoto, Alessandro , Tillema, Jan‐Mendelt , Valencia-Sánchez, Cristina , Sechi, Elia , Pittock, Sean J. , Flanagan, Eoin P.

Journal of Neurology, Neurosurgery & Psychiatry | July 20, 2025 | Volume: No volume available | Issue: No issue available | Pages: jnnp-2025-336684

10.1136/jnnp-2025-336684 | PMID 40685157 Get It

Background Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and multiple sclerosis (MS) have both overlapping and distinct MRI lesion features, which vary with imaging timing. This study identified distinguishing MRI characteristics using paired MRIs at clinical attack and remission. Methods We retrospectively identified Mayo Clinic patients with MOGAD and MS that: (1) fulfilled respective diagnostic criteria; (2) had paired attack (≤30 days) and remission MRI scans (≥12 months) without interval attacks. MRIs were compared between groups for key features. Results We included 43 patients with MOGAD (median age 31 years (range, 3–67); 63% female) and 49 patients with MS (median age 39 years (range, 17–65); 65% female). Resolution of at least one T2-lesion differentiated MOGAD from MS (sensitivity, (95% CI 77% to 100%), specificity, (95% CI 86% to 99%); Youden’s index (YI)=0.90). Resolution of at least two T2-lesions indicated MOGAD (sensitivity 62% (95% CI 41% to 79%); specificity, 100% (95% CI 94% to 100%); YI=0.62). MOGAD patients were more likely to have normal MRI scans at follow-up compared with MS (brain 14/44 (32%) vs 0/60 (0%), p<0.001; spine 21/27 (78%) vs 7/36 (19%), p<0.001). In addition, the presence of T1-hypointense, ovoid periventricular T2, and enhancing lesions were more common in MS versus MOGAD at attack and remission and in the spine, longitudinally extensive T2 lesions were more common in MOGAD attacks (8/27 (30%)). Conclusion Paired MRI at attack and remission revealed distinctive characteristics of MOGAD and MS, with greater diagnostic value at remission driven by the discriminating power of T2-lesion resolution. In MOGAD patients with initial parenchymal involvement, a 1-year follow-up MRI may aid diagnosis and serve as a new baseline.
Super-resolution ultrasound imaging of microvasculature: Initial experiences in preclinical and clinical applications
Huang, Chengwu , Lok, U‐Wai , Zhang, Jingke , DeRuiter, Ryan M. , Chen, Shigao

The Journal of the Acoustical Society of America | July 18, 2025 | Volume: 157 | Issue: 4_Supplement | Pages: A22-A22

10.1121/10.0037263 Get It

Ultrasound localization microscopy (ULM) enables imaging of the microvasculature at spatial resolutions surpassing the limits of conventional ultrasound, while maintaining comparable penetration depth. This super-resolution technique relies on the localization and tracking of individual microbubbles (MBs) administered into the bloodstream, providing detailed visualization of microvascular structures and functions. However, clinical implementation of ULM faces significant challenges, such as low signal-to-noise ratio (SNR), tissue motion artifacts, and prolonged acquisition times. In this presentation, we will discuss advancements aimed at achieving robust and reproducible clinical implementation of ULM through a series of technical innovations and optimizations. These include signal enhancement techniques to boost MB SNR, advanced algorithms for accurate MB localization and tracking at clinically relevant dosages, optimized data acquisition strategies tailored to clinical workflows, and the development of 3-D imaging capabilities. Through pilot preclinical and clinical studies, we demonstrate the feasibility and efficacy of ULM in various applications, including chronic kidney disease (CKD), kidney transplant, liver disease evaluation, and beyond, in both animal models and human subjects under clinical scanning conditions. These findings underscore the transformative potential of super-resolution ultrasound imaging as a diagnostic tool, paving the way for widespread clinical adoption.
From Oocyte to Blastocyst: A Comparison of IVF Embryo Attrition Rates Based on Ovarian Reserve
Chen, Valerie , Rauchfuss, Lauren Kendall , Li, Yan , Ainsworth, Alessandra J. , Babayev, Samir N. , Shenoy, Chandra C.

Fertility Science and Research | July 18, 2025 | Volume: 12 | Issue: No issue available | Pages: 20

10.25259/fsr_30_2025 Get It

Objectives The effect of ovarian reserve on expected in vitro fertilisation (IVF) attrition remains controversial. This study analyses IVF attrition rates based on ovarian reserve and stimulation protocol to create customised pre-treatment counselling tools for assisting clinicians in setting accurate patient expectations. Material and Methods We completed a retrospective chart review of 18–44-year-old patients who underwent IVF treatment at a single academic institution between January 1, 2013, and March 23, 2023. Cycle outcomes, number of retrieved oocytes, mature oocytes, fertilised embryos, and blastocysts were analysed for patients with polycystic ovary syndrome (PCOS), unexplained infertility, and diminished ovarian reserve (DOR). A Poisson regression model was used to compare oocyte maturation, fertilisation, and blastulation rates among groups, adjusted for age, body mass index, race, and insemination method. Results Three hundred and thirteen couples underwent a total of 385 IVF cycles analysed in this study. There were 109 patients who underwent 120 cycles in the unexplained infertility group (31% cycles), 133 patients with 143 cycles in the PCOS group (37% cycles), 40 patients with 45 cycles in the DOR antagonist stimulation group (12% cycles), and 39 patients with 77 cycles in the DOR minimal stimulation group (20% cycles). No differences in oocyte maturation, fertilisation, or blastulation rate were seen among PCOS or DOR antagonist cycle groups when compared to unexplained infertility. After adjusting for confounders, blastulation rate was higher for the DOR minimal stimulation group compared to unexplained infertility (1.37-fold change, p = 0.04). Conclusion Rates of oocyte maturation, fertilisation, and blastulation were similar among all antagonist protocol cycles regardless of ovarian reserve. However, patients with DOR who undergo minimal stimulation may have modestly higher blastulation rates compared to DOR patients who undergo the antagonist protocol.
Titin-related familial dilated cardiomyopathy: factors associated with disease onset
Johnson, Renée , Fletcher, Robert A. , Peters, Stacey , Ohanian, Monique , Soka, Magdalena , Smolnikov, Andrei , Abihider, Katherine E, Ackerman, Michael J. , Ader, Flavie , Akhtar, Mohammed , Ashley, Euan A. , Austin, Rachel , Baas, Annette F., Blouin, Jean‐Louis , Brown, Emily E. , Cannie, Douglas , Correnti, Gemma, Ferro, Matteo Dal , Dellefave‐Castillo, Lisa , Dooijes, Dennis , Dybro, Anne M. , Demri, Youssef Ed, Hachmi, Mohamed El , Escobar-López, Luis , Foye, Sarah , Gigli, Marta , López, Esther González , Goudal, Adeline , Graw, Sharon , Guipponi, Michel, Haan, Eric , Haas, Jan , Hammersley, Daniel , Hansen, Frederikke , Hey, Thomas Morris , Houweling, Arjan C. , Ingrey, A., Jabbour, Andrew , Jansweijer, Joeri A. , Jongbloed, Jan D.H. , Keogh, Anne , Deprez, Ronald H. Lekanne , Macciocca, Ivan , Mansencal, Nicolas , Mansour, Julia, Martinez‐Veira, Cristina, Medo, Kristen , Merlo, Marco , Michalak, Ewa , Monserrat, Lorenzo , Mountain, Helen , Murphy, Anne M. , Murray, Brittney , Pachter, Nicholas , Palmyre, Aurélien , Pereira, Naveen L. , Picard, Kermshlise, Prasad, Sanjay , Proukhnitzky, Julie , Pruny, Jean-François, Réant, Patricia , Ronan, Anne , Semsarian, Christopher , Storm, Garrett , Thomson, Kate , Thompson, Tina , Wallis, Mathew , Flagship, Australian Genomics Cardiac, Adès, Lesley C., Alankarage, Dimithu, almog, Morgan, Al-Shinnag, Mohammad , Barnett, Chris , Bodek, Simon , Boggs, Kirsten, Bray, Alessandra , Brown, Jaye, Burns, Charlotte , Cao, Michelle, Carr, Will, Casauria, Sarah , Chalinor, Heather V., Chang, Yu‐Chen , Charitou, Theodosia , Collins, Felicity, Correnti, Gemma, Cox, Kathy, Das, Debjani , Fazio, Paul De, Elzen, Nicola Den, Devery, Sophie , Dobbins, Julia , Elbracht-Leong, Stefanie, Enríquez, A. Juanico, Fatkin, Diane , Fear, Vanessa S. , Fine, Miriam, Garza, Denisse , Gongolidis, Laura, Gray, Belinda , Greer, Cassie, Haan, Eric, Haas, Mathilda, Hanna, Bernadette , Hayward, Janette, Herrera, Carmen, Hill, Adam P. , Hollingsworth, Georgie, Hollway, Georgina E. , Horton, Ari , Ingles, Jodie, Isbister, Joanne , Jane-Pantaleo, Sarah, Kelly, Andrew , King‐Smith, Sarah L., Lassman, Timo, Lipton, Jonathon, MacIntyre, Paul, Madelli, Evanthia O. , Martin, Ellenore , Medi, C., Metke, Alejandro, Morrish, A., Morwood, Jim, Mowat, David , Ng, Chai‐Ann , Nowak, Natalie , Martinez, Noelia Nunez, O'Sullivan, S. S. , Overkov, Angela, Perrin, Mark J. , Perry, Matthew , Pflaumer, Andreas , Phillips, Peta, Phuong, Thuan, Pope-Couston, Rachel, Poplawski, Nicola K., Punni, Preeti, Rajagopalan, Sulekha , Regan, Matthew, Rogers, Jonathan, Ryan, Mark , Sandaradura, Sarah A. , Schönrock, Nicole, Scuffham, Paul , Sherburn, Isabella, Sherlock, Mary-Clare, Smerdon, Carla, Smith, Janine , Smyth, Renee, Sy, Raymond W. , Tang, Dotti, Taylor, Shelby , Tchan, Michel , Trainer, Alison, Trivedi, Gunjan, Spaendonck‐Zwarts, Karin van , Vandenberg, Jamie I. , Verma, Kunal , Vidgen, Miranda E. , Vohra, Jitendra K. , Waddel-Smith, Kathryn, Weintraub, Robert G, Worgan, Lisa , Wornham, Linda, Wu, Kathy H. C. , Yeates, Laura , Zentner, Dominica, Arnott, Clare , Fokstuen, Siv , Meder, Benjamin , Giudicessi, John R. , Parikh, Victoria N. , Ware, James S. , Rooryck, Caroline , Lakdawala, Neal K. , Elliott, Perry , Charron, Philippe , Peña‐Peña, María Luisa, Mogensen, Jens , Rasmussen, Torsten B. , Seidman, Jonathan G. , Seidman, Christine E. , Riele, Anneline S.J.M. te , Pinto, Yigal M. , Christiaans, Imke , Fatkin, Diane, Gray, Belinda , Akhtar, Mohammed M , Amin, Ahmad S , Ashley, Euan A , Atherton, John J , Austin, Rachel , Baas, Annette F , Bagnall, Richard D , Ross, Samantha Barratt , Blouin, Jean-Louis , Brown, Emily E , Bundgaard, Henning , Cannie, Douglas , Chmielewski, Przemyslaw , Crespo-Leiro, Maria Generosa , Dal Ferro, Matteo , Dellefave-Castillo, Lisa M , Dominguez, Fernando , Dybro, Anne M , Ed Demri, Youssef , El Hachmi, Mohamed , Escobar-Lopez, Luis , Foye, Sarah Jajesnica , Franaszczyk, Maria , Gigli, Marta , Goudal, Adeline , Graw, Sharon , Guipponi, Michel , Haan, Eric , Hammersley, Daniel J , Hansen, Frederikke G , Hayward, Chris , Hey, Thomas Morris , Ho, Carolyn Y , Houweling, Arjan C , Jabbour, Andrew , Jansweijer, Joeri A , Jongbloed, Jan D H , Keogh, Anne M , Larrañaga-Moreira, Jose M , Lekanne Deprez, Ronald H , Macciocca, Ivan , Macdonald, Peter S , McDonough, Barbara , McGaughran, Julie , Medo, Kristen , Michalak, Ewa , Monserrat, Lorenzo , Mountain, Helen , Muller, Steven A , Murphy, Anne M , Oates, Emily C , Ormondroyd, Elizabeth , Pachter, Nicholas , Palmyre, Aurélien , Pereira, Naveen L , Proukhnitzky, Julie , Reant, Patricia , Richard, Pascale , Ronan, Anne , Sedaghat-Hamedani, Farbod , Semsarian, Christopher , Storm, Garrett , Stroeks, Sophie , Taylor, Matthew R G , Thomson, Kate , Thompson, Tina , van Tintelen, J Peter , Vissing, Christoffer Rasmus , Waddell-Smith, Kathryn E , Wallis, Mathew , Marian, Ali J , Fokstuen, Siv , Giudicessi, J R , Parikh, Victoria N , Piriou, Nicolas , Rooryck, Caroline , Lakdawala, Neal K , Mestroni, Luisa , van Spaendonck-Zwarts, Karin Y , Garcia-Pavia, Pablo , Peña-Peña, Maria Luisa , Christensen, Alex Hoerby , Bilińska, Zofia T , Rasmussen, Torsten B , Seidman, Jonathan G , Seidman, Christine E , Te Riele, Anneline S J M , Ware, James S , Gray, Belinda , Vandenberg, Jamie I , Fletcher, Robert A , Amin, Ahmad S. , Bundgaard, Henning , Crespo‐Leiro, María G. , Domínguez, Fernándo , Heymans, Stéphane , Ho, Carolyn Y. , Ingles, Jodie , James, Paul A. , McGaughran, Julie , Paldino, Alessia , Poplawski, Nicola Kazia , Prasad, Sanjay K , Syrris, Petros , Taylor, Matthew R.G. , Tintelen, J. Peter van , Zentner, Dominica , Flagship, Australian Genomics Cardiac, Barnett, Chris, Blue, Gillian M. , Bogwitz, Michael R. , Boughtwood, Tiffany F. , Brion, Marie‐Jo , Bryson‐Richardson, Robert J. , Burnett, Leslie , Chapman, Gavin , Chong, Belinda , Correnti, Gemma, Cox, Kathy, Cunningham, Fiona, Davis, Jason A. , Davis, Andrew M. , Silva, M. De , Dunwoodie, Sally L. , Dwyer, Nathan , Elliott, David A. , Enriquez, Annabel, Finlay, Keri , Giannoulatou, Eleni , Greer, Cassie, Harvey, Richard Paul , Herrera, Carmen, Hill, Adam, Howting, Denise A. , Jackson, Matilda R. , Johnson, Renee, Kirk, Edwin Philip , Kummerfeld, Sarah , Lunke, Sebastian , MacIntyre, Paul, Mallawaarachchi, Amali C. , Mathew, Jacob , Mattiske, Tessa , McLean, Alison K. , McNamara, James W. , Milnes, Di , Milward, Michael, O'Sullivan, Sinead, Patel, Chirag , Quinn, Michael C. , Raju, Hariharan , Rath, Emma M. , Regan, Matthew, Ryan, Mark, Singer, Emma S. , Stark, Zornitza , Taylor, Jessica, Thorpe, Jordan , Trivedi, Gunjan , Valente, Giulia , Wilson, Meredith , Winlaw, David Scott , Zentner, Dominica, Oh, Jae Won , James, Cynthia A. , Villa, Roberto Barriales , Wahbi, Karim , Mestroni, Luisa , Sinagra, Gianfranco , Watkins, Hugh , McNally, Elizabeth M. , Charron, Philippe , Verdonschot, Job A.J.

European Heart Journal | July 18, 2025 | Volume: 46 | Issue: 48 | Pages: 5240-5257

10.1093/eurheartj/ehaf380 | PMID 40796136 Get It

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 (&lt;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.
Monoclonal Anti–Platelet Factor 4 Antibodies in Recurrent Pregnancy Loss
Bavli, Natalie , Kanack, Adam J. , Splinter, Noah P., Mauch, Emily, Kohlhagen, Mindy , Murray, David, Chen, Dong , Pruthi, Rajiv K. , Padmanabhan, Anand , Mauch, Emily E, Ainsworth, Alessandra J. , McBane, Robert D. , Kohlhagen, Mindy C, Padmanabhan, Anand , Nishimura, Yoshito , Sarode, Ravi

New England Journal of Medicine | July 16, 2025 | Volume: 393 | Issue: 3 | Pages: 306-309

10.1056/nejmc2506014 | PMID 40673591 Get It

Regional effects of gantenerumab on neuroimaging biomarkers in the DIAN‐TU‐001 trial
Chen, Charles D., Jack, Clifford R. , Koeppe, Robert, Hornbeck, Russ C. , Koudelis, Deborah, Keefe, Sarah , Aggarwal, Neelum T. , Bird, Thomas D. , Black, Sandra E., Chhatwal, Jasmeer P. , Day, Gregory S. , Farlow, Martin R. , Gauthier, Serge , Honig, Lawrence S., Xiong, Chengjie , Masellis, Mario, Méndez, Patricio Chrem, Ringman, John M. , Snider, B. Joy, Salloway, Stephen, Dyck, Christopher H. van , Klein, Gregory , Clifford, David B. , Hassenstab, Jason , Mills, Susan L., Perrin, Richard J., Supnet, Charlene , Wang, Guoqiao , Xiong, Chengjie , Team, for the DIAN‐TU Study, Jack, Clifford R , Day, Gregory S , Xiong, Chengjie , Chen, Charles D , Hassenstab, Jason , Supnet-Bell, Charlene , McCullough, Austin , Gordon, Brian A. , Joseph‐Mathurin, Nelly , McKay, Nicole S. , Hobbs, Diana A. , Flores, Shaney , Allegri, Ricardo , Berman, Sarah , Black, Sandra E. , Brooks, William S. , Fox, Nick C. , Honig, Lawrence S. , Hsiung, Ging‐Yuek Robin , Jucker, Mathias , Masters, Colin L. , Schofield, Peter R. , Shimada, Hiroyuki , Suzuki, Kazushi , Cruchaga, Carlos , Li, Yan , McDade, Eric , Morris, John C. , Bateman, Randall J. , Benzinger, Tammie L.S. , Team, for the DIAN‐TU Study

Alzheimer's & Dementia | July 15, 2025 | Volume: 21 | Issue: 7 | Pages: No page available

10.1002/alz.70347 | PMID 40660741 Get It

Abstract INTRODUCTION Monoclonal anti‐amyloid therapies are now accessible, but how these treatments influence changes within the brain is still not clear. We investigated overall and regional change in amyloid removal, glucose metabolism, and atrophy in trial participants with dominantly inherited Alzheimer's disease (DIAD). METHODS In the DIAN‐TU‐001 trial, 92 carriers received gantenerumab or placebo and underwent serial neuroimaging assessments including [ 11 C]‐Pittsburgh compound‐B (PiB) positron emission tomography (PET), [ 18 F]‐fluoro‐2‐deoxyglucose (FDG) PET, and magnetic resonance imaging (MRI). RESULTS Gantenerumab significantly reduced PiB‐PET uptake overall and in most regions and showed no changes in FDG‐PET or MRI measures. Drug effects were associated with baseline PiB‐PET uptake, and the largest effects occurred in medial regions. DISCUSSION Treated DIAD participants, and especially those with higher amyloid burden, showed a decrease in PiB‐PET uptake, which was more pronounced in the basal ganglia and medial frontal structures. These results may inform patient response and future drug trial design. Highlights Gantenerumab unevenly decreased Aβ burden as measured by PiB‐PET across brain regions. The strongest decrease in PiB‐PET uptake was in basal ganglia and medial frontal structures. Variable drug effect on Aβ was partly due to the amount of burden present before treatment. There was no regional effect on FDG‐PET metabolism or MRI volumetrics after 4 years.