tbuckley/cabot-search huggingface dataset:
A First-in-Human Study of cinrebafusp alfa, a HER2/4-1BB Bispecific Molecule, in Patients with HER2-Positive Advanced Solid Malignancies
Authors: Sarina Piha-Paul, Shane A. Olwill, Erika Hamilton, Anthony Tolcher, Paula Pohlmann, Stephen V. Liu, Cornelia Wurzenberger, Laura-Carolin Hasenkamp, Eva-Maria Hansbauer, Rachna Shroff, Sara Hurvitz, Anuradha Krishnamurthy, Amita Patnaik, Noah Hahn, Raman Kumar, Manuela Duerr, Markus Zettl, Kayti Aviano, Louis Matis, Ingmar Bruns, Geoffrey Ku
Journal: Clinical Cancer Research (2024)

Abstract Purpose: 4-1BB (CD137) is a costimulatory immune receptor expressed on activated T cells, activated B cells, NK cells, and tumor-infiltrating lymphocytes, making it a promising target for cancer immunotherapy. Cinrebafusp alfa, a monoclonal antibody-like bispecific protein targeting HER2 and 4-1BB, aims to localize 4-1BB activation to HER2-positive tumors. This study evaluated the safety, tolerability, and preliminary efficacy of cinrebafusp alfa in patients with previously treated HER2-positive malignancies. Patients and Methods: This was a multicenter dose-escalation study involving patients with HER2-positive malignancies who received prior treatment. The study assessed the safety and efficacy of cinrebafusp alfa across various dose levels. Patients were assigned to different cohorts, and antitumor responses were evaluated. The study aimed to determine the MTD and to observe any clinical activity at different dose levels. Results: Of 40 evaluable patients in the “active dose” efficacy cohorts, five showed an antitumor response, resulting in an overall response rate of 12.5% and a disease-control rate of 52.5%. Clinical activity was observed at the 8 and 18 mg/kg dose levels, with confirmed objective response rates of 28.6% and 25.0%, respectively. Cinrebafusp alfa was safe and tolerable, with grade ≤2 infusion-related reactions being the most frequent treatment-related adverse event. MTD was not reached during the study. Conclusions: Cinrebafusp alfa demonstrates promising activity in patients with HER2-positive malignancies who have progressed on prior HER2-targeting regimens. Its acceptable safety profile suggests it could be a treatment option for patients not responding to existing HER2-directed therapies.
Inpatient Care and Outcomes Among People With Cancer Experiencing Homelessness
Authors: Kanan Shah, Patricia Mae G. Santos, Lillian A. Boe, Justin M. Barnes, Anna Tao, C. Jillian Tsai, Fumiko Chino
Journal: JAMA Oncology (2024)

Importance Cancer is a leading cause of death among people experiencing homelessness (PEH) in the US. Acute care settings are important sources of care for PEH; however, the association of housing status with inpatient care remains understudied, particularly in the context of cancer. Objective To assess whether housing status is associated with differences in the inpatient care of hospitalized adults with cancer. Design, Setting, and Participants This cross-sectional study included hospitalized inpatient adults aged 18 years or older diagnosed with cancer who were identified using data from the 2016 to 2020 National Inpatient Sample. Propensity score matching was used to create a cohort of PEH and housed individuals matched according to age, sex, race and ethnicity, insurance type, cancer diagnosis, number of comorbidities, substance use disorder, severity of illness, year of admission, hospital location, hospital ownership, region, and hospital bed size. Matched pairs were identified using a 1:1 nearest neighbor matching algorithm without replacement, accounting for survey weights. Data were analyzed from August 1, 2022, to April 30, 2024. Exposure Housing status. Main Outcomes and Measures The associations of receipt of invasive procedures, systemic therapy, or radiotherapy during hospitalization (primary outcomes) as well as inpatient death, high cost of stay, and discharge against medical advice (AMA) (secondary outcomes) with housing status. Odds ratios and 95% CIs were estimated with multivariable logistic regression, with adjustment for patient, disease, and hospital characteristics of the matched cohort. Results The unmatched cohort comprised 13 838 612 individuals (median [IQR] age, 67 [57-76] years; 7 329 473 males [53.0%]) and included 13 793 462 housed individuals (median [IQR] age, 68 [58-77] years) and 45 150 (median [IQR] age, 58 [52-64] years) individuals who were experiencing homelessness after accounting for survey weights. The PEH cohort had a higher prevalence of lung (17.3% vs 14.5%) and upper gastrointestinal (15.2% vs 10.5%) cancers, comorbid substance use disorder (70.2% vs 15.3%), and HIV (5.3% vs 0.5%). Despite having higher rates of moderate or major illness severity (80.1% vs 74.0%) and longer length of stay (≥5 days: 62.2% vs 49.1%), PEH were less likely to receive invasive procedures (adjusted odds ratio [AOR], 0.53; 95% CI, 0.49-0.56), receive systemic therapy (AOR, 0.73; 95% CI, 0.63-0.85), or have a higher-than-median cost of stay (AOR, 0.71; 95% CI, 0.65-0.77). Although PEH had lower rates of inpatient death (AOR, 0.79; 95% CI, 0.68-0.92), they were 4 times more likely to be discharged AMA (AOR, 4.29; 95% CI, 3.63-5.06). Conclusions and Relevance In this nationally representative cross-sectional study of hospitalized adults with cancer, disparities in inpatient care of PEH highlight opportunities to promote equitable cancer care in this socioeconomically vulnerable population.
Lynch Syndrome and Somatic Mismatch Repair Variants in Pancreas Cancer
Authors: Catherine A. O’Connor, Emily Harrold, David Lin, Henry Walch, Andrea Gazzo, Megha Ranganathan, Sarah Kane, Fergus Keane, Joshua Schoenfeld, Drew Moss, Deborah M. Thurtle-Schmidt, Sarah P. Suehnholz, Debyani Chakravarty, Fiyinfolu Balogun, Anna Varghese, Kenneth Yu, David Kelsen, Alicia Latham, Britta Weigelt, Wungki Park, Zsofia Stadler, Eileen M. O’Reilly
Journal: JAMA Oncology (2024)

Importance Microsatellite (MS) instability (MSI-H) occurs frequently in Lynch syndrome (LS)–associated tumors and is associated with response to immune checkpoint blockade (ICB) therapy. MSI-H is conferred by germline or somatic variants in mismatch repair genes. The contribution of somatic oncogenesis to MSI-H in pancreatic cancer (PC) is unknown. Objective To evaluate an LS-related PC cohort to define clinicogenomic features, describe somatic MSI-H cases (germline negative), characterize response to ICB, and guide preferred MS testing methods. Design, Setting, and Participants This single-institution, retrospective analysis was conducted from March 2012 to July 2023 at Memorial Sloan Kettering Cancer Center and included 55 patients with PC and either an LS germline pathogenic variant (gPV) or somatic mismatch repair (MMR) variant. Main Outcomes and Measures Composite MMR and MS status determined using orthogonal methods. An artificial intelligence classifier was used to account for low-cellularity specimens. Demographic and clinical data were abstracted from medical record. Zygosity status and somatic comutation landscape analyzed. Results Fifty-five patients (23 women [42%]) had PC and an MMR variant: 32 (58%) had LS (LS cohort) and 23 (42%) had a somatic MMR variant (no germline pathogenic variant, somatic MMR cohort). In the LS cohort, 10 (31%) had g MSH2 , 9 (28%) g MSH6 , 8 (25%) g PMS2 , 4 (13%) g MLH1 , 1 (3%) g EPCAM . The median age at diagnosis was 68 years (range, 45-88 years). For composite MS status, 17 (59%) were MSI-H, 12 (41%) MS stable, and 3 MS unknown. Five cases were reclassified as MSI-H by the artificial intelligence classifier. In the somatic MMR cohort, 11 (48%) had MSH6 , 7 (30%) MLH1 , 3 (13%) MSH2 , and 2 (9%) PMS2 . The median age at diagnosis was 72 years (range, 66-85 years). For composite MS status, 10 (43%) were MSI-H, 11 (48%) MS stable, and 2 (9%) MS indeterminate. Six cases were reclassified as MSI-H by the artificial intelligence classifier. For the LS and somatic MMR cohorts, 20 received ICB (n = 17 MSI-H). The median ICB duration was 27.7 months (95% CI, 11.5 to not reached); the disease control rate was 80%. Conclusion The results of this cross-sectional study suggest that MSI-H occurs due to LS or somatic oncogenesis in PC. Orthogonal MS testing is key in PC; the artificial intelligence classifier reclassified approximately 20% of cases, most of which were low cellularity. ICB for patients with LS or somatic MSI-H PC provided significant benefit.
Facile Size Tunable Skin‐Adaptive Patch for Accelerating Wound Healing
Authors: Sung‐Won Kim, Sangyul Baik, Jiyu Hyun, Jihyun Lee, Dohyun Lim, Tae‐Jin Lee, Gun‐Jae Jeong, Gwang‐Bum Im, Inwoo Seo, Yeong Hwan Kim, Changhyun Pang, Suk Ho Bhang
Journal: Advanced Healthcare Materials (2024)

Abstract Owing to the moist and curved interfaces of skin wounds, enhancing the adhesiveness while maintaining delivery efficacy of biomolecules has drawn significant attention in advanced wound dressings. Despite tremendous trials to load biomolecules with sound adhesiveness, the complicated fabricating processes and abnormal allergic responses that are attributed to chemical moiety‐based adhesives remain as major problems. To this end, in this study a one‐step fabrication process is developed to manufacture microstructures with both a therapeutic (cylindrical structure for embossed structure human adipose‐derived stem cell sheet, ESS) and an adhesive part (octopi‐inspired structure of adhesive, OIA), which ESOIA is called. OIA showed the highest adhesion strength in both dry (1.48 N cm −2 ) and wet pig skin conditions (0.81 N cm −2 ), maintaining the adhesive properties after repeated attach–detach trials. ESS from the therapeutic part of ESOIA also showed an enhanced angiogenic effect compared with the ones that are normally cultured in vitro. ESS also showed improved in vivo wound healing outcomes following enhanced cell engraftment compared to the cell injection group by means of intact cell‐extracellular matrix interactions.
Utilizing Continuous Glucose Monitoring for Early Detection of Gestational Diabetes and Pregnancy Outcomes in an Asian Population
Authors: Beth S.Y. Lim, Qian Yang, Mahesh Choolani, Daphne S.L. Gardner, Yap Seng Chong, Cuilin Zhang, Shiao-Yng Chan, Ling-Jun Li
Journal: Diabetes Care (2024)

OBJECTIVE We explored the potential value of continuous glucose monitoring (CGM) in early pregnancy in predicting gestational diabetes mellitus (GDM) and pregnancy outcomes. RESEARCH DESIGN AND METHODS The study recruited 103 multiethnic Asian pregnant women with overweight/obesity from a hospital-based, prospective cohort. All of them had worn blinded CGM devices in early pregnancy and underwent the universal GDM screening at 24–28 gestation weeks. Models were selected based on early pregnancy risk factors and CGM-derived parameters to compare their respective predictive values for GDM and pregnancy outcomes. RESULTS Eighteen GDM cases were ascertained. CGM-derived novel parameters demonstrated greater performance (e.g., area under the curve: 0.953 vs. 0.722) for predicting incident GDM compared with the model using traditional risks. Such novel CGM-derived parameters significantly differentiated primary cesarean and large-for-gestational age babies. CONCLUSIONS Our data suggest CGM's potential clinical utility in the first trimester for predicting GDM and adverse pregnancy outcomes, particularly in overweight or obese individuals.
Frequency of ERBB2-Low Expression in Endometrial Cancer
Authors: Camilla Krakstad, Hege F. Berg, Kristina Lindemann, Mari Kyllesø Halle
Journal: JAMA Oncology (2024)

This study reanalyzes epidermal growth factor receptor 2 (ERBB2) data from a previous study to characterize patient subgroups with ERBB2-low tumors.
Diagnosis, Risk Stratification, and Treatment of Pericarditis
Authors: Paul C. Cremer, Allan L. Klein, Massimo Imazio
Journal: JAMA (2024)

Pericarditis accounts for up to 5% of emergency department visits for nonischemic chest pain in North America and Western Europe. With appropriate treatment, 70% to 85% of these patients have a benign course. In acute pericarditis, the development of constrictive pericarditis (<0.5%) and pericardial tamponade (<3%) can be life-threatening.
Circulating Tumor DNA and Survival in Metastatic Breast Cancer
Authors: Kyle Dickinson, Archi Sharma, Ramana-Kumar Venkata Agnihotram, Selin Altuntur, Morag Park, Sarkis Meterissian, Julia V. Burnier
Journal: JAMA Network Open (2024)

Importance Metastatic breast cancer (MBC) poses a substantial clinical challenge despite advancements in diagnosis and treatment. While tissue biopsies offer a static snapshot of disease, liquid biopsy—through detection of circulating tumor DNA (ctDNA)—provides minimally invasive, real-time insight into tumor biology. Objective To determine the association between ctDNA and survival outcomes in patients with MBC. Data Sources An electronic search was performed in 5 databases (CINAHL, Cochrane Library, Embase, Medline, and Web of Science) and included all articles published from inception until October 23, 2023. Study Selection To be included in the meta-analysis, studies had to (1) include women diagnosed with MBC; (2) report baseline plasma ctDNA data; and (3) report overall survival, progression-free survival, or disease-free survival with associated hazards ratios. Data Extraction and Synthesis Titles and abstracts were screened independently by 2 authors. Data were pooled using a random-effects model. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses ( PRISMA ) reporting guideline, and quality was assessed using the Newcastle-Ottawa Scale. Main Outcomes and Measures The primary study outcome was the association between detection of specific genomic alterations in ctDNA with survival outcomes. Secondary objectives were associations of study methodology with survival. Results Of 3162 articles reviewed, 37 met the inclusion criteria and reported data from 4264 female patients aged 20 to 94 years. Aggregated analysis revealed a significant association between ctDNA detection and worse survival (hazard ratio, 1.40; 95% CI, 1.22-1.58). Subgroup analysis identified significant associations of TP53 and ESR1 alterations with worse survival (hazard ratios, 1.58 [95% CI, 1.34-1.81] and 1.28 [95% CI, 0.96-1.60], respectively), while PIK3CA alterations were not associated with survival outcomes. Stratifying by detection method, ctDNA detection through next-generation sequencing and digital polymerase chain reaction was associated with worse survival (hazard ratios, 1.48 [95% CI, 1.22-1.74] and 1.28 [95% CI, 1.05-1.50], respectively). Conclusions and Relevance In this systematic review and meta-analysis, detection of specific genomic alterations in ctDNA was associated with worse overall, progression-free, and disease-free survival, suggesting its potential as a prognostic biomarker in MBC. These results may help guide the design of future studies to determine the actionability of ctDNA findings.
68Ga-FAPI PET/CT Depicted the Fibrosis of Ischemic Colitis
Authors: Jieling Zheng, Qian Ru, Yun Yang, Weibing Miao
Journal: Clinical Nuclear Medicine (2024)

Abstract Ischemic colitis is the most common form of ischemic bowel disease; identification of ischemic colitis with PET/CT is rare. We present a case of unexplained ischemic colitis in a 66-year-old man who underwent 18 F-FDG PET/CT to exclude intestinal malignancy and was subsequently recruited in a clinical trial regarding 68 Ga-FAPI. 18 F-FDG PET/CT showed intense activity in the intestinal lumen where mucosa had chronic inflammation. Conversely, 68 Ga-FAPI PET/CT revealed high tracer uptake in the intestinal wall and adjacent mesentery. Our case showed the different distribution pattern of 18 F-FDG and 68 Ga-FAPI in ischemic colitis.
Accuracy of Clinical Staging in Early-Stage Pancreatic Ductal Adenocarcinoma
Authors: Gerardo Perrotta, Ghada Mohamed, Brent K. Larson, Arsen Osipov, Cristina R. Ferrone, Simon K. Lo, Srinivas Gaddam
Journal: JAMA (2024)

This study evaluates the accuracy of clinical staging in early-stage pancreatic ductal adenocarcinoma.
Peritoneal Metastasis of Osteosarcoma in 99mTc-MDP SPECT/CT Imaging
Authors: Chentian Shen
Journal: Clinical Nuclear Medicine (2024)

Abstract An 11-year-old boy with history of conventional high-grade osteosarcoma in the left distal femur was referred to our department for 99m Tc-MDP whole-body bone scan. In addition to multiple bone lesions and pleura, abnormal high radioactivity was found in the abdomen. SPECT/CT revealed diffuse peritoneal thickening with calcification and increased radioactive uptake, which suggest peritoneal metastases. The most common metastases of osteosarcoma can be found in bone and lungs, whereas peritoneal metastases are extremely rare.
Upper Gastrointestinal Mucosal Damage and Subsequent Risk of Parkinson Disease
Authors: Jocelyn J. Chang, Subhash Kulkarni, Trisha S. Pasricha
Journal: JAMA Network Open (2024)

Importance The gut-first hypothesis of Parkinson disease (PD) has gained traction, yet potential inciting events triggering Parkinson pathology from gut-related factors remain unclear. While Helicobacter pylori infection is linked to mucosal damage (MD) and PD, it is unknown how upper gastrointestinal MD from any source increases PD risk. Objective To evaluate any association between upper endoscopy findings of MD and subsequent clinical PD diagnosis. Design, Setting, and Participants This was a retrospective cohort study of patients with no PD history undergoing upper endoscopy with biopsy between January 2000 and December 2005, with final follow-up assessments completed July 31, 2023. The study was conducted within the Mass General Brigham system, a multicenter network in the greater Boston, Massachusetts, area. Patients with MD were matched 1:3 to patients without MD based on age, sex, and date of initial endoscopy. Exposure MD, defined as erosions, esophagitis, ulcers, or peptic injury, observed on upper endoscopy or pathology reports. Main Outcomes and Measures The relative risk of PD given a history of MD, estimated using incident rate ratio (IRR) and multivariate Cox proportional hazard ratios (HRs). Results Of 9350 patients, participants had a mean (SD) age of 52.3 (20.3) years; 5177 (55.4%) were male; and 269 (2.9%) were Asian, 737 (7.9%) Black, and 6888 (73.7%) White. Most participants underwent endoscopy between the ages of 50 and 64 years (2842 [30.4%]). At baseline, patients with MD were more likely to have a history of H pylori infection, proton-pump inhibitor use, chronic nonsteroidal anti-inflammatory drug use, gastroesophageal reflux disease, smoking, constipation, and dysphagia. The mean (SD) follow-up time was 14.9 (6.9) years for the whole cohort, during which patients with MD were more likely to develop PD (IRR, 4.15; 95% CI, 2.89-5.97; P &amp;amp;lt; .001) than those without MD, even after covariate adjustment (HR, 1.76; 95% CI 1.11-2.51; P = .01). Constipation, dysphagia, older age, and higher Charlson-Deyo Comorbidity Index were also associated with higher PD risk. Conclusions and Relevance In this cohort study, a history of upper gastrointestinal MD was associated with elevated risk of developing a clinical PD diagnosis. Increased vigilance among patients with MD for future PD risk may be warranted.
Bi‐Pt Heterojunction Cascade Reaction Platform for Sono‐Immunotherapy of Tumors via PANoptosis and Ferroptosis
Authors: Sijia Wu, Qian Wang, Jun Du, Lejin Zhu, Fujun Yang, Jiacheng Lu, Xueyu Li, Yuhao Li, Jingtao Cui, Yuqing Miao
Journal: Advanced Healthcare Materials (2024)

Abstract Sonodynamic therapy (SDT) represents a promising, noninvasive, and precise treatment modality for tumors, demonstrating significant potential in clinical applications. However, the efficiency of sonosensitizers in generating reactive oxygen species (ROS) is often limited by rapid electron‐hole recombination. In this study, BiF 3 @BiOI is synthesized via a co‐precipitation method, followed by in‐situ reduction to decorate it with Pt nanoparticles, resulting in BiF 3 @BiOI@Pt‐PVP (BBP) nanocomposite for enhancing SDT efficacy. The formation of the BiF 3 @BiOI heterojunction enhances charge separation ability. The decoration of Pt nanoparticles narrows the bandgap and alters the band positions and Fermi level of BBP, which can effectively mitigate the rapid recombination of electron‐hole pairs and facilitate a cascade reaction of ROS, thereby improving ROS generation efficiency with ultrasound excitation. Additionally, bismuth ions in BBP and the generated holes consume glutathione, exacerbating cellular oxidative damage, and triggering PANoptosis and ferroptosis. Furthermore, Pt nanoparticles demonstrate peroxidase‐like activity, catalyzing endogenous hydrogen peroxide to oxygen. These functions are helpful against tumors for alleviating hypoxic conditions, reshaping the microenvironment, modulating immune cell infiltration capacity, and enhancing the efficacy of immunotherapy. The dual strategy of forming heterojunctions and sensitization with noble metals effectively enhances the efficacy of sono‐catalytic therapy‐induced immune activation in tumor treatment.
Liver and Kidney Tumor Masses as the Initial Presentation of B-Cell Acute Lymphoblastic Leukemia
Authors: Xiaoyu Liu, Jianping Zhong
Journal: Clinical Nuclear Medicine (2024)

Abstract We described a 13-year-old girl who presented unexplained paroxysmal sharp pain in the right upper abdomen for 3 days. CT and MRI showed multiple masses in the liver and kidneys, initially diagnosed as lymphoma. The hepatic mass biopsy confirmed B-cell lymphoblastic lymphoma. FDG PET/CT examination found that the liver and kidney masses demonstrated high metabolic activity, with concomitant increased metabolic activity in the skeleton. Bone marrow biopsy revealed extensive skeletal involvement. The final diagnosis was B-cell acute lymphoblastic leukemia. This case highlights the effectiveness of FDG PET/CT as an adjunct imaging modality for diagnosis.