tbuckley/cabot-search huggingface dataset:
High-Grade Progression, Sarcomatous Transformation, and/or Metastasis of Pituitary Neuroendocrine Neoplasms (PitNENs): The UCSF Experience
Authors: Merryl Terry, Minh P. Nguyen, Vivian Tang, Ekin Guney, Krishna L. Bharani, Sonika Dahiya, Ondrej Choutka, Ewa Borys, Gerald Reis, Lewis Blevins, Manish K. Aghi, Sandeep Kunwar, John DeGroot, David R. Raleigh, Melike Pekmezci, Andrew W. Bollen, Soonmee Cha, Nancy M. Joseph, Arie Perry
Journal: Endocrine Pathology (2024)

Pituitary neuroendocrine tumors (PitNET) that metastasize comprise ~ 0.2% of adenohypophyseal tumors are aggressive and are challenging to treat. However, many non-metastatic tumors are also aggressive. Herein, we review 21 specimens from 13 patients at UCSF with metastatic PitNETs (CSF or systemic, N = 7 patients), high-grade pituitary neuroendocrine neoplasms (HG-PitNEN, N = 4 patients), and/or PitNETs with sarcomatous transformation (PitNET-ST, N = 5 patients). We subtyped cases using the World Health Organization (WHO) and International Agency for Research on Cancer (IARC) criteria for neuroendocrine neoplasms (NENs). Lineage subtypes included acidophil stem cell, null cell, thyrotroph, corticotroph, lactotroph, and gonadotroph tumors. The median Ki-67 labeling index was 25% (range 5-70%). Lack of p16 was seen in 3 cases, with overexpression in 2. Strong diffuse p53 immunopositivity was present in 3 specimens from 2 patients. Loss of Rb expression was seen in 2 cases, with ATRX loss in one. Molecular analysis in 4 tumors variably revealed TERT alterations, homozygous CDKN2A deletion, aneuploidy, and mutations in PTEN, TP53, PDGFRB, and/or PIK3CA. Eight patients (62%) died of disease, 4 were alive at the last follow-up, and 1 was lost to the follow-up. All primary tumors had worrisome features, including aggressive lineage subtype, high mitotic count, and/or high Ki-67 indices. Additional evidence of high-grade progression included immunohistochemical loss of neuroendocrine, transcription factor, and/or hormone markers. We conclude that metastatic PitNET is not the only high-grade form of pituitary NEN. If further confirmed, these histopathologic and/or molecular features could provide advanced warning of biological aggressiveness and be applied towards a future grading scheme.
18F-THK5351 PET Is Superior to Conventional MRI in Identifying Inflammatory Lesions by Imaging Astrogliosis in 2 Cases of Neurosyphilis
Authors: Risa Kotani, Keiko Hatano, Kenji Ishibashi, Atsushi Iwata
Journal: Clinical Nuclear Medicine (2024)

18 F-labeled THK5351 PET can visualize ongoing astrogliosis by estimating monoamine oxidase B levels and can be used as a neuroinflammation marker for identifying inflammatory lesions by imaging astrogliosis. Assessment of its performance is of interest, especially when compared with conventional MRI. Here, we present 2 cases of neurosyphilis, in which 18 F-THK5351 PET identified inflammatory lesions by imaging astrogliosis, whereas MRI had difficulty detecting the lesions. Hence, this study suggests that 18 F-THK5351 PET is superior to conventional MRI in identifying inflammatory lesions and that this feature of 18 F-THK5351 can provide insights into the pathophysiology of neurosyphilis in living patients.
Size matters: integrating tumour volume and immune activation signatures predicts immunotherapy response
Authors: Su Yin Lim, Ines Pires da Silva, Nurudeen A. Adegoke, Serigne N. Lo, Alexander M. Menzies, Matteo S. Carlino, Richard A. Scolyer, Georgina V. Long, Jenny H. Lee, Helen Rizos
Journal: Molecular Cancer (2024)

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, providing significant benefit to patients across various tumour types, including melanoma. However, around 40% of melanoma patients do not benefit from ICI treatment, and accurately predicting ICI response remains challenging. We now describe a novel and simple approach that integrates immune-associated transcriptome signatures and tumour volume burden to better predict ICI response in melanoma patients. RNA sequencing was performed on pre-treatment (PRE) tumour specimens derived from 32 patients with advanced melanoma treated with combination PD1 and CTLA4 inhibitors. Of these 32 patients, 11 also had early during treatment (EDT, 5–15 days after treatment start) tumour samples. Tumour volume was assessed at PRE for all 32 patients, and at first computed tomography (CT) imaging for the 11 patients with EDT samples. Analysis of the Hallmark IFNγ gene set revealed no association with ICI response at PRE (AUC ROC curve = 0.6404, p = 0.24, 63% sensitivity, 71% specificity). When IFNg activity was evaluated with tumour volume (ratio of gene set expression to tumour volume) using logistic regression to predict ICI response, we observed high discriminative power in separating ICI responders from non-responders (AUC = 0.7760, p = 0.02, 88% sensitivity, 67% specificity); this approach was reproduced with other immune-associated transcriptomic gene sets. These findings were further replicated in an independent cohort of 23 melanoma patients treated with PD1 inhibitor. Hence, integrating tumour volume with immune-associated transcriptomic signatures improves the prediction of ICI response, and suggest that higher levels of immune activation relative to tumour burden are required for durable ICI response.
A German perspective on the impact of socioeconomic status in diffuse large B-cell lymphoma
Authors: Susanne Ghandili, Judith Dierlamm, Carsten Bokemeyer, Henrik Kusche, Frederik Peters
Journal: Blood Cancer Journal (2024)

Abstract The prognostic influence of socioeconomic status (SES) on the survival of diffuse large B-cell lymphoma (DLBCL) patients remains controversial. This observational study examines the potential impact of regional SES inequalities on overall survival (OS) among DLBCL patients in Germany. We analyzed data from the German nationwide population-based dataset spanning 2004-2019 sourced from the German Center for Cancer Registry Data ( n = 49,465). The primary objective was to assess the 5-year OS among patients with low SES compared to those living in middle and high SES areas. SES was grouped according to quintiles of the German Index of Socioeconomic Deprivation, which summarized nine indicators covering aspects of regional education, employment, and income. DLBCL patients in low SES areas had significantly impaired 5-year OS compared to those in middle and high SES regions (59.2% vs. 61.8% vs. 64.1%, p &lt; 0.0001). Yet, additionally accounting for regional premature mortality removed the impact of SES on survival (Hazard Ratio 0.94, 95% CI 0.87–1.01). Our findings indicate that the prognostic impact of socioeconomic deprivation on long-term survival is not due to variations in diagnosis and treatment of DLBCL itself but rather a higher comorbidity burden.
Phage-liposome nanoconjugates for orthopedic biofilm eradication
Authors: Lei Wang, Tamta Tkhilaishvili, Zheng Jiang, Rima Fanaei Pirlar, Yu Ning, Adrián Millán Laleona, Jiaxing Wang, Jin Tang, Qiaojie Wang, Andrej Trampuz, Mercedes Gonzalez Moreno, Xianlong Zhang
Journal: Journal of Controlled Release (2024)

Infection by multidrug-resistant (MDR) bacteria has become one of the biggest threats to public health worldwide. One reason for the difficulty in treatment is the lack of proper delivery strategies into MDR bacterial biofilms, where the thick extracellular polymeric substance (EPS) layer impedes the penetration of antibiotics and nanoparticles. Here, we propose a novel bioactive nanoconjugate of drug-loaded liposomes and bacteriophages for targeted eradication of the MDR biofilms in orthopedic infections. Phage Sb-1, which has the ability to degrade EPS, was conjugated with antibiotic-loaded liposomes. Upon encountering the biofilm, phage Sb-1 degrades the EPS structure, thereby increasing the sensitivity of bacteria to antibiotics and allowing the antibiotics to penetrate deeply into the biofilm. As a result, effective removal of MDR bacterial biofilm was achieved with low dose of antibiotics, which was proved in this study by both in vitro and in vivo investigations. Notably, in the rat prosthetic joint infection (PJI) model, we found that the liposome-phage nanoconjugates could effectively decrease the bacterial load in the infected area and significantly promote osteomyelitis recovery. It is therefore believed that the conjugation of bacteriophage and liposomes could open new possibilities for the treatment of orthopedic infections, possibly other infections in the deep tissues.
Autophagy activator-loaded bicomponent peptide nanocarriers for phototherapy-triggered immunity enhancement against metastatic breast cancer
Authors: Teng Ma, Danqi Li, Zhuo-Ran Yang, Qi Wang, Rong Chen, Niannian Lv, Kehan Du, Huimin Qin, Juan Tao, Hao Jiang, Jintao Zhu
Journal: Journal of Controlled Release (2024)
Crosstalk between macrophages and mesenchymal stem cells shape patterns of osteogenesis and immunomodulation in mineralized collagen scaffolds
Authors: Vasiliki Kolliopoulos, Maxwell Polanek, Melisande Wong Yan Ling, Aleczandria Tiffany, Kara L. Spiller, Brendan A.C. Harley
Journal: Bioactive Materials (2024)
Angiogenesis-osteogenesis coupling and anti-osteoclastogenesis zoledronate intermixed calcium silicate metal-organic/inorganic hybrid coating on biodegradable zinc-based intramedullary nails for osteoporotic fracture healing
Authors: Junyu Qian, Haotian Qin, En Su, Jiaming Hou, Hui Zeng, Tianbing Wang, Deli Wang, Guojiang Wan, Yingqi Chen
Journal: Bioactive Materials (2024)
Clinical and subclinical acute brain injury caused by invasive cardiovascular procedures
Authors: Radosław Lenarczyk, Marco Proietti, Jan F. Scheitz, Dipen Shah, Eberhard Siebert, Diana A. Gorog, Jacek Kowalczyk, Nikolaos Bonaros, George Ntaios, Wolfram Doehner, Nicolas M. Van Mieghem, Sandor Nardai, Jan Kovac, Roland Fiszer, Roberto Lorusso, Eliano Navarese, Sergio Castrejón, Andrea Rubboli, José Miguel Rivera-Caravaca, Alaide Chieffo, Gregory Y. H. Lip
Journal: Nature Reviews Cardiology (2024)

Over the past 50 years, the number and invasiveness of percutaneous cardiovascular procedures globally have increased substantially. However, cardiovascular interventions are inherently associated with a risk of acute brain injury, both periprocedurally and postprocedurally, which impairs medical outcomes and increases health-care costs. Current international clinical guidelines generally do not cover the area of acute brain injury related to cardiovascular invasive procedures. In this international Consensus Statement, we compile the available knowledge (including data on prevalence, pathophysiology, risk factors, clinical presentation and management) to formulate consensus recommendations on the prevention, diagnosis and treatment of acute brain injury caused by cardiovascular interventions. We also identify knowledge gaps and possible future directions in clinical research into acute brain injury related to cardiovascular interventions.
Recombinant Zoster Vaccination Among US Veterans Receiving Immunosuppressive Medications
Authors: Sharon Abada, Jing Li, Gary Tarasovsky, Cherish Wilson, Jinoos Yazdany, Mary A. Whooley, Gabriela Schmajuk
Journal: JAMA Network Open (2024)

This cross-sectional study investigates rates of recombinant zoster vaccination among US veterans receiving immunosuppressive medications before and after expanded indications for younger adults who are immunocompromised.
External Validation of the American Heart Association PREVENT Cardiovascular Disease Risk Equations
Authors: Britton Scheuermann, Alexandra Brown, Trenton Colburn, Hisham Hakeem, Chen Hoe Chow, Carl Ade
Journal: JAMA Network Open (2024)

Importance The American Heart Association’s Predicting Risk of Cardiovascular Disease Events (PREVENT) equations were developed to extend and improve on previous cardiovascular disease (CVD) risk assessments for the purpose of treatment initiation and patient-clinician communication. Objective To assess prognostic capabilities, calibration, and discrimination of the PREVENT equations in a study sample representative of the noninstitutionalized, US general population. Design, Setting, and Participants This prognostic study used data from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2010 data cycles. Participants included adults for whom 10-year follow-up data were available. Data curation and analyses took place from December 2023 through May 2024. Main Outcomes and Measures Primary measures were risk estimated by the PREVENT equations, as well as risk estimates from the previous Pooled Cohort Equations (PCEs). The primary outcome was composite CVD-related mortality at 10 years of follow-up. Additional analyses compared the PREVENT equations against the PCEs. Model discrimination was assessed with receiver-operator characteristic curves and Harrell C statistic from proportional hazard regression; model calibration was determined as the slope of predicted versus observed risk. Results The study cohort, accounting for NHANES complex survey design, consisted of 172.9 million participants (mean age, 45.0 years [95% CI, 44.6-45.4 years]; 52.1% women [95% CI, 51.5%-52.6%]). In analyses adjusted for the NHANES survey design, a 1% increase in PREVENT risk estimates was statistically significantly associated with increased CVD mortality risk (hazard ratio, 1.090; 95% CI, 1.087-1.094). PREVENT risk scores demonstrated excellent discrimination (C statistic, 0.890; 95% CI, 0.881-0.898) but moderate underfitting of the model (calibration slope, 1.13; 95% CI, 1.06-1.21). PREVENT risk models performed statistically significantly better than the PCEs, as assessed by the net reclassification index (0.093; 95% CI, 0.073-0.115). Conclusions and Relevance In this prognostic study of the PREVENT equations, PREVENT risk estimates demonstrated excellent discrimination and only modest discrepancies in calibration. These findings provided evidence supporting utilization of the PREVENT equations for application in the intended population as suggested by the American Heart Association.
More Than Half of US Adults With Uncontrolled Hypertension Don’t Know They Have It
Authors: Samantha Anderer
Journal: JAMA (2024)

More than half—58%—of US adults aged 18 years or older with uncontrolled hypertension were unaware they had the condition in a study using nationally representative survey data. And 71% of those who were aware and took medication still couldn't control their blood pressure, researchers found.
Long COVID Among Undocumented Latino Immigrant Populations in the Emergency Department
Authors: Karen P. Reyes, Zubaid Rafique, Brian Chinnock, Vijaya Arun Kumar, Michael Gottlieb, Kristin L. Rising, Robert M. Rodriguez
Journal: JAMA Network Open (2024)

This cross-sectional study assesses the understanding of and access to care for long COVID symptoms among undocumented Latino immigrants in US emergency departments (EDs).
Study: Single Dose of Modified Smallpox Vaccine Effective for Mpox
Authors: Samantha Anderer
Journal: JAMA (2024)

A single dose of the modified vaccinia Ankara–Bavarian Nordic (MVA-BN) smallpox vaccine is 58% effective against mpox infection, according to a study in The BMJ. The results were based on 9800 men aged 18 years or older in Canada and come as mpox cases continue to spread in regions of Africa.
Sleep and Wellness in Residency—Embracing the Shift
Authors: Bharati Prasad, Vineet M. Arora
Journal: JAMA Network Open (2024)

Stijn A. A. Massar, PhD; Xin Yu Chua, BSocSci; Ruth Leong, PhD; Hosein A. Golkashani, MD, PhD; Zhenghao Pu, BSc; Alyssa S. C. Ng, BA; Ju Lynn Ong, PhD; Chun Siong Soon, PhD; Nicholas B. H. Ng, MBBS; Mae Yue Tan, MBBS; Jeremy B. Lin, MBBS; Marion Aw, MBBS; Michael W. L. Chee, MBBS
Trends in Prevalence of Early Introduction of Complementary Foods to US Children, 2016 to 2022
Authors: Guodong Ding, Anqi Peng, Yan Chen, Angela Vinturache, Yongjun Zhang
Journal: JAMA Network Open (2024)

This cross-sectional study analyzes temporal changes in prevalence of early complementary food introduction to US children from 2016 to 2022 and provides up-to-date evidence of this nutrition practice.
Validating the PREVENT Equations—A Contemporary Update to Cardiovascular Risk Assessment
Authors: Sridhar Mangalesh, Michael G. Nanna
Journal: JAMA Network Open (2024)

Britton Scheuermann, MS; Alexandra Brown, PhD; Trenton Colburn, PhD; Hisham Hakeem, MD; Chen Hoe Chow, MD; Carl Ade, MS, PhD
Urinary Cytokeratin 20 as a Biomarker for AKI-CKD Transition among Patients with Acute Decompensated Heart Failure and AKI
Authors: Han Ouyang, Rui Ma, Xiaobing Yang, Chunbo Chen, Xin Xu, Jianwei Tian, Jun Liu, Yan Zha, Huafeng Liu, Tiecheng Yang, Fan Fan Hou
Journal: Journal of the American Society of Nephrology (2024)

Key Points In patients with acute decompensated heart failure and AKI, higher urinary cytokeratin 20 (CK20) associated with higher risk of AKI-to-CKD progression. Urinary CK20, particularly combined with clinical variables, improved the ability of predicting AKI-CKD transition with an accuracy of 90%. Urinary CK20 might be used as a novel tool for early identifying patients at high risk of kidney function loss after AKI. Background Predicting the risk of AKI-CKD transition remains a major challenge in the management of acute decompensated heart failure (ADHF) and AKI. This study investigated the clinical utility of urinary cytokeratin 20 (CK20), a novel biomarker reflecting the severity of histological acute tubular injury, for identifying patients at risk of AKI-to-CKD progression. Methods This prospective cohort study included a test set comprising 279 consecutive hospitalized patients with ADHF and AKI in five centers and a validation set enrolling 206 similar patients at an external center. Urinary CK20 and seven reported renal tubular injury biomarkers at the time of AKI diagnosis were measured. The primary outcome was a composite of AKI-CKD transition 90 days after AKI or all-cause death within 90 days. The secondary outcome was AKI-to-CKD progression 90 days after AKI. Results In the test set, 115 patients (41%) reached the primary end point. Concentrations of urinary CK20 peaked on the day of AKI diagnosis and remained elevated 14 days after AKI. After multivariable adjustment, the highest tertile of urinary CK20 was associated with 21-fold higher risk of the primary outcome and 29-fold higher risk of the secondary outcome. For predicting the primary and secondary outcomes, urinary CK20 at the time of AKI diagnosis had an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI], 0.77 to 0.87) and 0.81 (95% CI, 0.75 to 0.87), respectively, and outperformed other reported biomarkers reflecting acute tubular injury and risk of CKD. Adding urinary CK20 to the clinical variables improved the ability for predicting the primary outcome with an area under the receiver operating characteristic curve of 0.90 (95% CI, 0.85 to 0.94) and largely improved risk reclassification. The ability of urinary CK20 in predicting AKI-CKD transition was further confirmed in the validation set. Conclusions Urinary CK20 improved prediction of the risk of transition from AKI to CKD in patients with ADHF and AKI.
In Vivo tissue healing mechanism at the intestinal anastomosis site following high-frequency electric welding
Authors: Caihui Zhu, Yuyan Na, Zhengqing Yan, Xiujun Cheng, Pengyao Xie, Xiaonan Tao, Lei Chen, Hui Zhao, Jian Qiu, Xiaodong Gu, Jian bin Xiang, Kefu Liu
Journal: International Journal of Surgery (2024)

To investigate the effect of High-Frequency Electric Welding (HFEW) on intestinal tissue healing, we performed end-to-end anastomosis experiments in New Zealand rabbits. Within one week post-surgery, animals exhibited normal vital signs, replaced necrotic tissue with healthy collagen, and showed improved tissue strength while inflammation decreased. By day 60, tissue pathology and function fully recovered, resembling normal tissue. Healing at the anastomotic site occurred in three phases: immediate adhesion, inflammation, and remodeling, with macrophages crucial for phagocytosis and regeneration of necrotic tissue. This study enhances understanding of HFEW’s healing mechanisms and supports further preclinical investigations.
Safety and Efficacy of Avacopan in Patients with C3 Glomerulopathy
Authors: Andrew S. Bomback, Leal C. Herlitz, Priyanka Punit Kedia, Jeffrey Petersen, Huibin Yue, Richard A. Lafayette
Journal: Journal of the American Society of Nephrology (2024)

Key Points ACCOLADE was the first randomized trial in patients with complement 3 glomerulopathy investigating the use of avacopan, a complement component 5a receptor blocker. The trial did not meet its primary end point of change in disease activity index from baseline to 26 weeks. No new safety signals were reported; the results suggest a potential role of avacopan in milder forms of complement 3 glomerulopathy. Background Complement 3 (C3) glomerulopathy is a rare autoimmune disorder characterized by activation of the alternative complement pathway with isolated or dominant complement 3 deposition in glomeruli. Patients with C3 glomerulopathy may develop progressive deterioration in kidney function and kidney failure. Methods We studied the safety and efficacy of avacopan 30 mg twice daily in patients with C3 glomerulopathy ( N =57) with elevated (&gt;244 ng/ml) and normal (≤244 ng/ml) levels of membrane attack complex or terminal complement complex (C5b-9) in a randomized, double-blind, placebo-controlled, phase 2 trial, with kidney biopsies performed prerandomization and at 26 and 52 weeks. The primary outcome was the percent change from baseline to week 26 in C3 Glomerulopathy Histological Index for disease activity. Results The study was conducted in patients with C3 glomerulopathy, including C3 GN and dense deposit disease. The median study duration was 60.0 weeks (interquartile range, 59.9–61.0). There were no significant differences in the primary outcome between the avacopan and the placebo group—least squares mean treatment difference (95% confidence interval)= −0.0 (−1.9 to 1.8). The secondary measures of efficacy including C3 Glomerulopathy Histological Index for disease chronicity, urine protein:creatinine ratio, and eGFR were not different between treatment groups. The overall incidence and type of adverse events for both treatment groups were comparable. No deaths were reported during the study, and no new safety signals were detected. Conclusions The primary end point for the study was not met; other clinical effects of avacopan to improve certain key kidney function parameters and slow disease progression were variable and require further evaluation. Clinical Trial registry name and registration number: Controlled Trial Evaluating Avacopan in C3 Glomerulopathy (ACCOLADE), NCT03301467.
Electronic Nudges to Increase Influenza Vaccination in Patients With Chronic Diseases
Authors: Niklas Dyrby Johansen, Muthiah Vaduganathan, Ankeet S. Bhatt, Daniel Modin, Safia Chatur, Brian L. Claggett, Kira Hyldekær Janstrup, Carsten Schade Larsen, Lykke Larsen, Lothar Wiese, Michael Dalager-Pedersen, Lars Køber, Scott D. Solomon, Pradeesh Sivapalan, Jens Ulrik Stæhr Jensen, Cyril Jean-Marie Martel, Tyra Grove Krause, Tor Biering-Sørensen
Journal: JAMA (2024)

Despite strong worldwide guideline recommendations, influenza vaccination rates remain suboptimal among young and middle-aged patients with chronic diseases. Effective scalable strategies to increase vaccination are needed.