tbuckley/cabot-search huggingface dataset:
Abstract MP21: Findings From A Community-based Hypertension Screening Program In Rural Nepal
Authors: Dinesh Neupane, Sweta Koirala, Abhinav Vaidya, Lawrence J Appel, Kuni Matsushita
Journal: Circulation (2022)

Introduction: Hypertension is the leading cause of morbidity and mortality in low- and middle-income countries (LMICs). However, data on the prevalence of hypertension in rural areas are limited. Aim: To characterize the prevalence of hypertension in rural areas of Nepal. Methods: Data were collected from two rural municipalities (Rupa and Biruwa) of Nepal as a part of the baseline assessment of quasi-experimental study evaluating whether community-health workers can diagnose and treat hypertension, the MUTU study (NCT 04521582). We surveyed all residents of the municipalities aged 25 to 70 years at their homes during April-July 2021. Three blood pressures (BP) at the home visit were obtained; the average of the last two readings was analyzed. Results: A total of 10,974 adults were screened. Average systolic and diastolic BP (SBP and DBP) were 125.6 (SD 20.3) and 84.2 (SD 11.9) mmHg; 27.7% (n=3,048) had high SBP &gt; 140 and/or DBP &gt; 90 mmHg (‘high BP’). Of all screenees, 13.1% had unrecognized high BP, and 1.7% had BP ≥180/120 mmHg (‘very high BP’). Of those with high BP, 52.8% were aware, 16.9% (n=483) were taking antihypertensive medication, and 6.2% (n=191) had BP ≥180/120 mmHg. Of 2,123 participants with high BP eligible for MUTU (exclusion criteria: BP medication, heart diseases, diabetes, breast-feeding, pregnant, and planned migration), 2,049 participants had BP measured again 1-2 weeks later, and hypertension was confirmed in 1,432 participants (69.9%). See figure. Of these, 5.8% had isolated elevated SBP, and 33.8% isolated elevated DBP; most (60.4%) had elevated SBP and DBP. Conclusions: In this home-based BP screening program conducted in rural Nepal, ~13% of adults aged 25-70 years had unrecognized high BP, including ~2% with BP ≥180/120 mmHg. These results highlight the importance of community-based BP screening as well as the need for effective treatment programs in rural communities
Pineal Yolk Sac Tumor Producing α-Fetoprotein Detected by 68Ga-FAPI PET/MRI
Authors: Yaqing Dai, Yizhen Pang, Weiqi Bao, Yuanyuan Cheng, Haojun Chen
Journal: Clinical Nuclear Medicine (2021)

Abstract Pineal yolk sac tumors (YSTs) are a rare type of extragonadal YST. They make up a small fraction of all intracranial germ cell tumors and an even small fraction of pineal masses overall. This study reported a case of pineal YST with α-fetoprotein production revealed by 18 F-FDG and 68 Ga-FAPI PET/MRI. In the PET images, 68 Ga-FAPI showed a far better tumor-to-background ratio than 18 F-FDG in the pineal YST because there is little 68 Ga-FAPI uptake in the brain. This case indicates that 68 Ga-FAPI PET/MRI may be a useful tool for evaluating intracranial YST and other types of tumors in central nervous system.
Metabolic risk factors and effect of alirocumab on cardiovascular events after acute coronary syndrome: a post-hoc analysis of the ODYSSEY OUTCOMES randomised controlled trial
Authors: Petr Ostadal, Philippe Gabriel Steg, Yann Poulouin, Deepak L Bhatt, Vera A Bittner, Terrence Chua, Rafael Diaz, Shaun G Goodman, Yong Huo, Johan Wouter Jukema, Yuri Karpov, Robert Pordy, Michel Scemama, Michael Szarek, Harvey D White, Gregory G Schwartz
Journal: The Lancet Diabetes & Endocrinology (2022)
COVID-19 Lung Findings Detected by 68Ga-PSMA PET/CT for Staging Purposes in Patients With Prostate Cancer
Authors: Burcin Karasah Erkek, Özgür Ömür, Serdar Özkök, Burak Turna
Journal: Clinical Nuclear Medicine (2021)

Abstract We report 3 patients with COVID-19 findings in 68 Ga-PSMA PET/CT taken for staging. The first patient, A 64-year-old man with prostate cancer, who had COVID-19 in November 2020 and whose treatment was completed, was observed to continue with COVID-19 findings in 68 Ga-PSMA PET/CT in December 2020 before surgery. Other patients were asymptomatic for the disease. It was determined that a PSMA uptake in the lungs corresponding to the CT findings of COVID-19 had increased in 68 Ga-PSMA PET/CT.
Abstract EP10: Obesity Is An Independent Risk Factor For Type 2 Myocardial Infarction-related Hospitalizations Without Significant Association With In-Hospital Mortality
Authors: Akhil Jain, Waleed Sultan, Nitin Ghadge, Crystal Moras, Siva Naga Yarrarapu, Kartik Dhaduk, Hasnan Ijaz, Mohammed Ghazi Moh'd Qaryouti, Rupak Desai
Journal: Circulation (2022)

Background: Contemporary data for the impact of obesity (BMI&gt;30) on the risk of demand ischemia-related myocardial infarction (i.e. type 2; T2MI) and subsequent outcomes is lacking. We aimed to study the risk and outcomes of T2MI with obesity. Methods: We used National Inpatient Sample (2018) to identify adult hospitalizations with T2MI (excluded concurrent T1MI). Multivariable regression was performed to assess the risk of T2MI with obesity. Using propensity-matched analysis obese vs non-obese cohorts (1:1) were obtained to compare comorbidities and primary outcomes (in-hospital mortality/cardiogenic shock). Results: Obese had higher odds of T2MI (OR 1.11, 95%CI:1.05-1.17, p&lt;0.001) when adjusted for confounders. Propensity-matched cohorts ( Table 1 , n=6220 obese &amp; non-obese, each) were comparable for sociodemographics with higher rates of diabetes, hyperlipidemia, COPD, CKD, deficiency anemia, prior history of MI/CABG but lower hypertension, smoking, CHF, PVD, substance abuse, prior stroke than non-obese. Association of obesity did not reach a significant level of difference for all-cause in-hospital mortality (OR 0.93, 95% CI: 0.51-1.70) and cardiogenic shock (OR 1.42, 95%CI 0.75-2.69). Length of stay was similar (3 days) but obese patients with type MI had a higher mean cost of hospitalization. Conclusion: Obesity independently predicted a higher risk of developing T2MI but without any significant association with short-term all-cause in-hospital mortality or cardiogenic shock.
18F-FMISO PET Imaging Identifies Hypoxia and Immunosuppressive Tumor Microenvironments and Guides Targeted Evofosfamide Therapy in Tumors Refractory to PD-1 and CTLA-4 Inhibition
Authors: Kirsten M. Reeves, Patrick N. Song, Allyson Angermeier, Deborah Della Manna, Yufeng Li, Jianbo Wang, Eddy S. Yang, Anna G. Sorace, Benjamin M. Larimer
Journal: Clinical Cancer Research (2021)

Hypoxia is a common characteristic of many tumor microenvironments, and it has been shown to promote suppression of antitumor immunity. Despite strong biological rationale, longitudinal correlation of hypoxia and response to immunotherapy has not been investigated.In this study, we probed the tumor and its surrounding microenvironment with 18F-FMISO PET imaging to noninvasively quantify tumor hypoxia in vivo prior to and during PD-1 and CTLA-4 checkpoint blockade in preclinical models of breast and colon cancer.Longitudinal imaging identified hypoxia as an early predictive biomarker of therapeutic response (prior to anatomic changes in tumor volume) with a decreasing standard uptake value (SUV) ratio in tumors that effectively respond to therapy. PET signal correlated with ex vivo markers of tumor immune response including cytokines (IFNγ, GZMB, and TNF), damage-associated molecular pattern receptors (TLR2/4), and immune cell populations (macrophages, dendritic cells, and cytotoxic T cells). Responding tumors were marked by increased inflammation that were spatially distinct from hypoxic regions, providing a mechanistic understanding of the immune signaling pathways activated. To exploit image-guided combination therapy, hypoxia signal from PET imaging was used to guide the addition of a hypoxia targeted treatment to nonresponsive tumors, which ultimately provided therapeutic synergy and rescued response as determined by longitudinal changes in tumor volume.The results generated from this work provide an immediately translatable paradigm for measuring and targeting hypoxia to increase response to immune checkpoint therapy and using hypoxia imaging to guide combinatory therapies.
Medicare Coverage of Vaccines—A Work in Progress
Authors: Francis J. Crosson
Journal: JAMA Internal Medicine (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Reply to T. Gupta et al
Authors: Isao Oze, Naoyuki Kohno, Yasuhisa Hasegawa
Journal: Journal of Clinical Oncology (2022)

We thank Gupta et al 1 for their letter in response to our article. 2Elective neck dissection (END) is useful for patients with early-stage oral cancer with a high potential for cervical lymph node metastasis.By contrast, patients with a low potential for cervical lymph node metastasis are initially treated with therapeutic neck dissection (ND) after the appearance of late metastasis.END and therapeutic ND have caused over-and underoperation, respectively, and END often leads to functional problems.By contrast, therapeutic ND can preserve function.Therefore, the advantages and disadvantages of END and therapeutic ND in terms of prognosis and function are two sides of the same coin.In 2015, a randomized controlled trial (RCT) conducted at the Tata Memorial Centre concluded the long debate on the respective use of observation and END as a treatment strategy for early-stage oral cancer. 3Currently, END is considered a standard of care for early-stage oral cancer.Sentinel lymph node biopsy (SLNB) is an alternative strategy that complements the disadvantages of END.
Antiangiogenesis: Vessel Regression, Vessel Normalization, or Both?
Authors: Hellmut G. Augustin, Gou Young Koh
Journal: Cancer Research (2022)

Abstract The concepts of antiangiogenic tumor therapy were pioneered on the assumption that the inhibition of tumor angiogenesis should lead to the complete regression of the tumor-associated vasculature and thereby hold the tumor in an avascular dormant state. Yet, clinical trials revealed limited efficacy of angiogenesis inhibitors when used as monotherapy. Instead, antiangiogenic drugs proved effective to extend overall survival when used in combination with chemotherapy. This counterintuitive observation—inhibition of tumor vascularization should lead to less and not more delivery of chemotherapy to the tumor—led to the concepts of “vessel normalization.” This refers to the notion that antiangiogenic drugs prune the most immature tumor vessels and spare mature vessels, thereby resulting in a more normal-appearing vasculature that leads to better access of chemotherapy to the tumor. The concepts of vessel normalization were first laid out in a landmark publication in Cancer Research in 2004. More than 600 studies on different aspects of vessel normalization have been published since then. Nevertheless, it is to this day less clear than ever to what extent vessel regression (leading to tumor starvation) and vessel normalization (facilitating chemotherapy) contribute to the clinical efficacy of antiangiogenic tumor therapy. This “Landmark Commentary” puts the concepts of tumor vessel normalization in historical context and develops thereupon some of the most burning questions in the field of translational angiogenesis research that need to be answered to further advance the application of tumor vascular stroma reprogramming therapies. See related article by Tong and colleagues, Cancer Res 2004;64:3731–6.
14P Flat-dose nivolumab (NIVO) as second-line (2L) treatment (tx) in Asian patients (pts) with advanced non-small cell lung cancer (NSCLC): CheckMate 870 long-term results
Authors: S. Lu, Y. Cheng, J. Zhou, M. Wang, J. Zhao, B. Wang, G. Chen, J. Feng, Z. Ma, L. Wu, C. Wang, K. Ma, S. Zhang, J. Liang, Y. Song, J. Wang, Y-L. Wu, A. Li, Y. Huang, J. Chang
Journal: Annals of Oncology (2022)
What's in a Name? That Which We Call Immune Cells by Any Other Name Would All Smell as Sweet
Authors: Roberto Salgado, Sherene Loi
Journal: Clinical Cancer Research (2022)

Summary In the FUTURE-C-Plus phase II trial, patients with advanced previously untreated immune-enriched triple-negative breast cancer achieved an overall objective response rate of 81.3% with the combination of camrelizumab, famitinib, and nab-paclitaxel. This supports that the quantity of immune cells is important for identifying those with response to treatments combined with PD-1–targeting immunotherapy. See related article by Chen et al., p. 2807
Ectopic Retrolaryngeal Parathyroid Adenoma Detected by 18F-Ethylcholine PET/US Fusion Imaging
Authors: Philipp Seifert, Julia Greiser, Thomas Winkens, Kerstin Lorenz, Martin Freesmeyer
Journal: Clinical Nuclear Medicine (2021)

A 68-year-old woman was referred with the diagnosis of symptomatic pHPT (primary hyperparathyroidism). Ultrasonography (US) and 99mTc-MIBI scintigraphy could not clearly identify a parathyroid adenoma. A primary unilateral surgical exploration remained unsuccessful to remove adenomatous parathyroid tissue and the pHPT persisted. 18F-ethylcholine PET/CT showed a left-sided retropharyngeal lesion with intense tracer uptake that could not be detected on US images at first sight. Therefore, additional 18F-ethylcholine PET/US fusion imaging was performed and revealed a poorly definable nodular structure on US that could be unambiguously correlated to the PET finding. Surgical excision confirmed an oncocytic variant of parathyroid adenoma, and parathormone and calcium levels normalized immediately.
Spatial Mapping and Immunomodulatory Role of the OX40/OX40L Pathway in Human Non–Small Cell Lung Cancer
Authors: Angelo Porciuncula, Micaela Morgado, Richa Gupta, Kostas Syrigos, Robert Meehan, Sima J. Zacharek, Joshua P. Frederick, Kurt A. Schalper
Journal: Clinical Cancer Research (2021)

To evaluate the tissue distribution and clinical significance of OX40 and OX40L in human non-small cell lung cancer (NSCLC).Using multiplexed quantitative immunofluorescence, we conducted simultaneous and localized measurements of OX40 and OX40L proteins, major T-cell subsets, and conventional type 1 dendritic cells (cDC1) in 614 primary NSCLCs from three independent cohorts represented in tissue microarrays. We also measured OX40L protein in samples from a phase I clinical trial of intratumor administration of a lipid nanoparticle encapsulated mRNA encoding OX40L (mRNA-2416) in human solid tumors. Finally, we studied the OX40 pathway in 212 uterine/ovarian serous carcinomas.OX40 protein was expressed in approximately 90% of NSCLCs, and OX40L was detected in approximately 10% of cases. Increased expression of OX40 was associated with higher CD4+ and CD8+ T lymphocytes, as well as cDC1s. Elevated expression of OX40L was consistently associated with increased CD4+ tumor-infiltrating lymphocytes and longer overall survival. No association was found between OX40 or OX40L levels and oncogenic driver mutations in EGFR and KRAS in lung adenocarcinomas. Delivering OX40L mRNA using intratumor mRNA-2416 injection mediated increased local OX40L protein levels that was most prominent in a patient with ovarian serous carcinoma. Detectable OX40L protein levels were observed in 15% of primary uterine/ovarian serous malignancies and associated with longer survival.The OX40 pathway is expressed in a fraction of NSCLCs and is associated with a favorable immune contexture. Although OX40L is uncommonly expressed in NSCLC and serous malignancies, it is associated with better prognosis and can be introduced using exogenous mRNA.
Chemotherapy and Targeted Therapy for Patients With Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That is Either Endocrine-Pretreated or Hormone Receptor–Negative: ASCO Guideline Update
Authors: Beverly Moy, R. Bryan Rumble, Steven E. Come, Nancy E. Davidson, Angelo Di Leo, Julie R. Gralow, Gabriel N. Hortobagyi, Douglas Yee, Ian E. Smith, Mariana Chavez-MacGregor, Rita Nanda, Heather L. McArthur, Laura Spring, Katherine E. Reeder-Hayes, Kathryn J. Ruddy, Paul S. Unger, Shaveta Vinayak, William J. Irvin, Avan Armaghani, Michael A. Danso, Natalie Dickson, Sophie S. Turner, Cheryl L. Perkins, Lisa A. Carey
Journal: Journal of Clinical Oncology (2021)

This guideline updates recommendations of the ASCO guideline on chemotherapy and targeted therapy for patients with human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC) that is either endocrine-pretreated or hormone receptor (HR)-negative.An Expert Panel conducted a targeted systematic literature review guided by a signals approach to identify new, potentially practice-changing data that might translate into revised guideline recommendations.The Expert Panel reviewed abstracts from the literature review and retained 14 articles.Patients with triple-negative, programmed cell death ligand-1-positive MBC may be offered the addition of immune checkpoint inhibitor to chemotherapy as first-line therapy. Patients with triple-negative, programmed cell death ligand-1-negative MBC should be offered single-agent chemotherapy rather than combination chemotherapy as first-line treatment, although combination regimens may be offered for life-threatening disease. Patients with triple-negative MBC who have received at least two prior therapies for MBC should be offered treatment with sacituzumab govitecan. Patients with triple-negative MBC with germline BRCA mutations previously treated with chemotherapy may be offered a poly (ADP-ribose) polymerase inhibitor rather than chemotherapy. Patients with HR-positive human epidermal growth factor receptor 2-negative MBC for whom chemotherapy is being considered should be offered single-agent chemotherapy rather than combination chemotherapy, although combination regimens may be offered for highly symptomatic or life-threatening disease. Patients with HR-positive MBC with disease progression on an endocrine agent may be offered treatment with either endocrine therapy with or without targeted therapy or single-agent chemotherapy. Patients with HR-positive MBC with germline BRCA mutations no longer benefiting from endocrine therapy may be offered a poly (ADP-ribose) polymerase inhibitor rather than chemotherapy. No recommendation regarding when a patient's care should be transitioned to hospice or best supportive care alone is possible.Additional information is available at www.asco.org/breast-cancer-guidelines.
Urinary Proteomics Identifies Cathepsin D as a Biomarker of Rapid eGFR Decline in Type 1 Diabetes
Authors: Christine P. Limonte, Erkka Valo, Viktor Drel, Loki Natarajan, Manjula Darshi, Carol Forsblom, Clark M. Henderson, Andrew N. Hoofnagle, Wenjun Ju, Matthias Kretzler, Daniel Montemayor, Viji Nair, Robert G. Nelson, John F. O’Toole, Robert D. Toto, Sylvia E. Rosas, John Ruzinski, Niina Sandholm, Insa M. Schmidt, Tomas Vaisar, Sushrut S. Waikar, Jing Zhang, Peter Rossing, Tarunveer S. Ahluwalia, Per-Henrik Groop, Subramaniam Pennathur, Janet K. Snell-Bergeon, Tina Costacou, Trevor J. Orchard, Kumar Sharma, Ian H. de Boer
Journal: Diabetes Care (2022)

OBJECTIVE Understanding mechanisms underlying rapid estimated glomerular filtration rate (eGFR) decline is important to predict and treat kidney disease in type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS We performed a case-control study nested within four T1D cohorts to identify urinary proteins associated with rapid eGFR decline. Case and control subjects were categorized based on eGFR decline ≥3 and &amp;lt;1 mL/min/1.73 m2/year, respectively. We used targeted liquid chromatography–tandem mass spectrometry to measure 38 peptides from 20 proteins implicated in diabetic kidney disease. Significant proteins were investigated in complementary human cohorts and in mouse proximal tubular epithelial cell cultures. RESULTS The cohort study included 1,270 participants followed a median 8 years. In the discovery set, only cathepsin D peptide and protein were significant on full adjustment for clinical and laboratory variables. In the validation set, associations of cathepsin D with eGFR decline were replicated in minimally adjusted models but lost significance with adjustment for albuminuria. In a meta-analysis with combination of discovery and validation sets, the odds ratio for the association of cathepsin D with rapid eGFR decline was 1.29 per SD (95% CI 1.07–1.55). In complementary human cohorts, urine cathepsin D was associated with tubulointerstitial injury and tubulointerstitial cathepsin D expression was associated with increased cortical interstitial fractional volume. In mouse proximal tubular epithelial cell cultures, advanced glycation end product–BSA increased cathepsin D activity and inflammatory and tubular injury markers, which were further increased with cathepsin D siRNA. CONCLUSIONS Urine cathepsin D is associated with rapid eGFR decline in T1D and reflects kidney tubulointerstitial injury.
Neuronal Autophagy Regulates Presynaptic Neurotransmission by Controlling the Axonal Endoplasmic Reticulum
Authors: Marijn Kuijpers, Gaga Kochlamazashvili, Alexander Stumpf, Dmytro Puchkov, Aarti Swaminathan, Max Thomas Lucht, Eberhard Krause, Tanja Maritzen, Dietmar Schmitz, Volker Haucke
Journal: Neuron (2022)

(Neuron 109, 299–313.e1–e9; January 20, 2021) The authors noticed two inadvertent errors in their publication. In Figure 6G, the DAPI channels of the wild-type and knockout brain slices were erroneously swapped. In Figure S5A, an incorrect representative immunoblot for calnexin was shown that originated from a different experiment. The corrected Figures 6G and S5A are shown below. These corrections do not affect the analysis of data or statements in the text and do not affect the conclusion of this paper. The authors sincerely apologize for both errors.Figure S5ALoss of ATG5 does not affect mitochondrial acidification, axonal lipid levels or ER integrityView Large Image Figure ViewerDownload Hi-res image Download (PPT) Neuronal Autophagy Regulates Presynaptic Neurotransmission by Controlling the Axonal Endoplasmic ReticulumKuijpers et al.NeuronNovember 5, 2020In BriefAutophagy is crucial for nervous system function. However, its physiological substrates are largely unknown. Kuijpers et al. demonstrate, using knockout mice conditionally lacking the essential autophagy protein ATG5 and quantitative proteomics paired with electrophysiology and functional imaging experiments, that neuronal autophagy regulates presynaptic neurotransmission by controlling the axonal endoplasmic reticulum. Full-Text PDF Open Access