tbuckley/cabot-search huggingface dataset:
The EASL–Lancet Commission on liver health in Europe: prevention, case-finding, and early diagnosis to reduce liver-related mortality
Authors: Tom H Karlsen, Harry Rutter, Patrizia Carrieri, Shira Zelber-Sagi, Eivind Engebretsen, Sharon Hutchinson, Kristin Voigt, Neil Guha, Annalisa Berzigotti, Georg Schomerus, Pere Gines, Maria Buti, Patrizia Burra, Michael P Manns, Aleksander Krag, Sabine Kleinert
Journal: The Lancet (2024)
Baseline ctDNA gene alterations as a biomarker of survival after panitumumab and chemotherapy in metastatic colorectal cancer
Authors: Kohei Shitara, Kei Muro, Jun Watanabe, Kentaro Yamazaki, Hisatsugu Ohori, Manabu Shiozawa, Atsuo Takashima, Mitsuru Yokota, Akitaka Makiyama, Naoya Akazawa, Hitoshi Ojima, Yasuhiro Yuasa, Keisuke Miwa, Hirofumi Yasui, Eiji Oki, Takeo Sato, Takeshi Naitoh, Yoshito Komatsu, Takeshi Kato, Ikuo Mori, Kazunori Yamanaka, Masamitsu Hihara, Junpei Soeda, Toshihiro Misumi, Kouji Yamamoto, Riu Yamashita, Kiwamu Akagi, Atsushi Ochiai, Hiroyuki Uetake, Katsuya Tsuchihara, Takayuki Yoshino
Journal: Nature Medicine (2024)

Abstract Certain genetic alterations and right-sided primary tumor location are associated with resistance to anti-epidermal growth factor (EGFR) treatment in metastatic colorectal cancer (mCRC). The phase 3 PARADIGM trial ( n = 802) demonstrated longer overall survival with first-line anti-EGFR (panitumumab) versus antivascular endothelial growth factor (bevacizumab) plus modified FOLFOX6 in patients with RAS wild-type mCRC with left-sided primary tumors. This prespecified exploratory biomarker analysis of PARADIGM ( n = 733) evaluated the association between circulating tumor DNA (ctDNA) gene alterations and efficacy outcomes, focusing on a broad panel of gene alterations associated with resistance to EGFR inhibition, including KRAS , NRAS, PTEN and extracellular domain EGFR mutations, HER2 and MET amplifications, and ALK , RET and NTRK1 fusions. Overall survival was prolonged with panitumumab plus modified FOLFOX6 versus bevacizumab plus modified FOLFOX6 in patients with ctDNA that lacked gene alterations in the panel (that is, negative hyperselected; median in the overall population: 40.7 versus 34.4 months; hazard ratio, 0.76; 95% confidence interval, 0.62–0.92) but was similar or inferior with panitumumab in patients with ctDNA that contained any gene alteration in the panel (19.2 versus 22.2 months; hazard ratio, 1.13; 95% confidence interval, 0.83–1.53), regardless of tumor sidedness. Negative hyperselection using ctDNA may guide optimal treatment selection in patients with mCRC. ClinicalTrials.gov registrations: NCT02394834 and NCT02394795 .
Association between peripheral endothelial function and myocardial perfusion in patients with coronary artery disease
Authors: Niklas Vartiainen, Juha E K Hartikainen, Tiina M Laitinen, Paavo-Ilari Kuikka, Hanna Mussalo, Tomi P Laitinen
Journal:  (2024)

Abstract Aims Endothelial dysfunction is a systemic disorder and risk factor for atherosclerosis. Our aim was to assess whether there is a relation between peripheral endothelial function and myocardial perfusion in patients with coronary artery disease (CAD). Methods and results We prospectively studied 54 patients, who had a positive result for obstructive CAD in coronary CT angiography. Myocardial perfusion (15O)H2O positron emission tomography was imaged at rest and during adenosine-induced maximal vasodilation. Peripheral endothelial function was assessed by measuring flow-mediated dilation (FMD) with ultrasound from the left brachial artery. There was a statistically significant correlation between FMD and global hyperaemic myocardial blood flow (MBF; r = 0.308, P = 0.023). The correlation remained statistically significant when controlling for gender, height, and diastolic blood pressure at rest (r = 0.367, P = 0.008). Receiver operating character analysis, however, yielded an area under curve of only 0.559 (P = 0.492) when FMD was used to predict reduced MBF (below 2.3 mL/g/min). Patients with significantly decreased MBF (n = 14) underwent invasive coronary angiography. FMD showed an inverse correlation with the severity of the most significant stenosis (r = −0.687, P = 0.007). Conclusion Peripheral endothelial function is related with hyperaemic MBF and with the severity of CAD in invasive coronary angiography. Due to insufficient sensitivity and specificity in the identification of reduced MBF, FMD is not suitable for clinical practice at the individual level. However, it works at the population level as a research tool when assessing endothelial dysfunction in patients with CAD.
Corticosteroids impair epithelial regeneration in immune-mediated intestinal damage
Authors: Viktor Arnhold, Winston Y. Chang, Suze A. Jansen, Govindarajan Thangavelu, Marco Calafiore, Paola Vinci, Ya-Yuan Fu, Takahiro Ito, Shuichiro Takashima, Anastasiya Egorova, Jason Kuttiyara, Adam Perlstein, Marliek van Hoesel, Chen Liu, Bruce R. Blazar, Caroline A. Lindemans, Alan M. Hanash
Journal: Journal of Clinical Investigation (2024)

Corticosteroid treatment (CST) failure is associated with poor outcomes for patients with gastrointestinal graft-versus-host disease (GI GVHD). CST is intended to target the immune system, but the glucocorticoid receptor is widely expressed, including within the intestines, where its effects are poorly understood. Here, we report that corticosteroids directly target intestinal epithelium, potentially worsening immune-mediated GI damage. Corticosteroids administered to mice in vivo and intestinal organoid cultures ex vivo reduced epithelial proliferation. Following irradiation, immediate CST mitigated GI damage, but delayed treatment attenuated regeneration and exacerbated damage. In a murine steroid-refractory GVHD model, CST impaired epithelial regeneration, worsened crypt loss, and reduced intestinal stem cell (ISC) frequencies. CST also exacerbated immune-mediated damage in organoid cultures with "steroid-refractory" GR-deficient T cells or Interferon-γ. These findings correlated with corticosteroid-dependent changes in apoptosis-related gene expression and STAT3-related epithelial proliferation. Conversely, Interleukin-22 administration enhanced STAT3 activity and overcame corticosteroid-mediated attenuation of regeneration, reducing crypt loss and promoting ISC expansion in steroid-treated mice with GVHD. Therefore, CST has the potential to exacerbate GI damage if it fails to control the damage-inducing immune response, but this risk may be countered by strategies augmenting epithelial regeneration, thus providing rationale for clinical approaches combining such tissue-targeted therapies with immunosuppression.
MMR vaccination induces trained immunity via functional and metabolic reprogramming of γδ T cells
Authors: Rutger J. Röring, Priya A. Debisarun, Javier Botey-Bataller, Tsz Kin Suen, Özlem Bulut, Gizem Kilic, Valerie A.C.M. Koeken, Andrei Sarlea, Harsh Bahrar, Helga Dijkstra, Heidi Lemmers, Katharina L. Gössling, Nadine Rüchel, Philipp N. Ostermann, Lisa Müller, Heiner Schaal, Ortwin Adams, Arndt Borkhardt, Yavuz Ariyurek, Emile J. de Meijer, Susan L. Kloet, Jaap ten Oever, Katarzyna Placek, Yang Li, Mihai G. Netea
Journal: Journal of Clinical Investigation (2024)

The measles, mumps and rubella (MMR) vaccine protects against all-cause mortality in children, but the immunological mechanisms mediating these effects are poorly known. We systematically investigated whether MMR can induce long-term functional changes in innate immune cells, a process termed trained immunity, that could at least partially mediate this heterologous protection. In a randomized placebo-controlled trial, 39 healthy adults received either the MMR vaccine or a placebo. By using single-cell RNA-sequencing, we found that MMR caused transcriptomic changes in CD14-positive monocytes and NK cells, but most profoundly in γδ T cells. Monocyte function was not altered by MMR vaccination. In contrast, the function of γδ T cells was markedly enhanced by MMR vaccination, with higher production of TNF and IFNγ, as well as upregulation of cellular metabolic pathways. In conclusion, we describe a trained immunity program characterized by modulation of γδ T cell function induced by MMR vaccination.
Abatacept inhibits inflammation and onset of rheumatoid arthritis in individuals at high risk (ARIAA): a randomised, international, multicentre, double-blind, placebo-controlled trial
Authors: Juergen Rech, Koray Tascilar, Melanie Hagen, Arnd Kleyer, Bernhard Manger, Verena Schoenau, Axel J Hueber, Stefan Kleinert, Xenofon Baraliakos, Jürgen Braun, Uta Kiltz, Martin Fleck, Andrea Rubbert-Roth, David M Kofler, Frank Behrens, Martin Feuchtenberger, Michael Zaenker, Reinhard Voll, Nils Venhoff, Jens Thiel, Cornelia Glaser, Eugen Feist, Gerd R Burmester, Kirsten Karberg, Johannes Strunk, Juan D Cañete, Ladislav Senolt, Maria Filkova, Esperanza Naredo, Raquel Largo, Gerhard Krönke, Maria-Antonietta D'Agostino, Mikkel Østergaard, Georg Schett
Journal: The Lancet (2024)
Safety and efficacy of atogepant for the preventive treatment of episodic migraine in adults for whom conventional oral preventive treatments have failed (ELEVATE): a randomised, placebo-controlled, phase 3b trial
Authors: Cristina Tassorelli, Krisztián Nagy, Patricia Pozo-Rosich, Michel Lanteri-Minet, Sara Sacco, Tomáš Nežádal, Hua Guo, Rosa De Abreu Ferreira, Giovanna Forero, Joel M Trugman
Journal: The Lancet Neurology (2024)
Mismatch Between Brain MRIs and 18F-DOPA PET/CT
Authors: Vincent Bourbonne, Brieg Dissaux, Romuald Seizeur, Jessica Nguyen, Solène Querellou
Journal: Clinical Nuclear Medicine (2024)

Abstract After receiving erlotinib for 4 years, a man with advanced lung adenocarcinoma was treated with stereotactic radiotherapy for a left cerebellar brain metastasis. Local relapse of the metastasis was suspected 14 months after and confirmed on 18 F-DOPA PET. Three additional uptakes were described with no unequivocal MRI pathological signal. A second radiotherapy course was delivered. One year later, isolated local recurrence was suspected on a 3 T MRI, with a suspicious 18 F-DOPA uptake. Five additional 18 F-DOPA uptakes were described among which one increased between the 2 PETs. Because of these MRI/PET mismatches, a switch from erlotinib to osimertinib was preferred over surgery.
Coexistence of Langerhans Cell Histiocytosis and Ganglioneuroblastoma Revealed by 18F-FDG PET/CT in a Pediatric Patient
Authors: Yanfeng Xu, Xia Lu, Wei Wang, Jigang Yang
Journal: Clinical Nuclear Medicine (2024)

Abstract Coexistence of Langerhans cell histiocytosis and ganglioneuroblastoma is rare and seldom reported in the literature. A 3-year-old girl with Langerhans cell histiocytosis underwent 18 F-FDG PET/CT imaging for staging, which demonstrated significant 18 F-FDG accumulation in the mandibles. Unexpectedly, a mild hypermetabolic soft mass was detected in the upper retroperitoneum. Results of surgical pathology of the abdominal mass were consistent with ganglioneuroblastoma.
How Early Can Checkpoint Inhibitors Induce a Complete Metabolic Response in Chemorefractory Hodgkin Lymphoma?
Authors: Angeliki N. Georgopoulou, Calliope Zerzi, Vaios Samaras, Phivi Rondogianni, Theodoros P. Vassilakopoulos
Journal: Clinical Nuclear Medicine (2024)

Abstract A 24-year-old man with classical Hodgkin lymphoma was lost to follow-up after metabolic complete remission (mCR). He presented 4 years later with B-symptoms and impaired clinical condition. Relapsed classical Hodgkin lymphoma was diagnosed. PET/CT revealed stage IVB with liver and spleen involvement. Two liver function–adjusted salvage attempts were ineffective. Pembrolizumab was instituted with gradual clinical improvement. PET was missed before treatment for a life-threatening condition and was performed on day +10 showing a near mCR. A mCR was confirmed before cycle 2, on day +21, underlining—for the first time in the literature—the possibility to achieve very early mCR with pembrolizumab.
Neuroendocrine Tumor Presented With Axillary Mass
Authors: María de las Nieves Sicilia Pozo, Fernando López-Bermejo García, Niletys Ruiz Disotuar, Lorena Alarcón Molero, Víctor Manuel Poblete García
Journal: Clinical Nuclear Medicine (2024)

Abstract A 79-year-old man presented with a palpable left axillary mass and ultrasonography findings of conglomerate lymph nodes. The initial clinical suspicion was a lymphoproliferative disorder, but histopathological results revealed a grade 3 neuroendocrine tumor. The mass showed somatostatin receptor overexpression in 99m Tc-HYNIC-TOC scintigraphy and high uptake in 18 F-FDG PET/CT. Bilateral hypermetabolic adrenal nodes suggestive of metastases were also detected. The patient was treated with chemotherapy and immunotherapy, and PET/CT scan showed a partial metabolic response after 4 cycles. According to this case, neuroendocrine tumor should be considered in the differential diagnosis of axillary masses.
Unusual Presence of Synchronous Primary Ovarian and Thyroid Extranodal Non-Hodgkin Lymphoma Without Lymph Node Involvement
Authors: Gündüzalp Buğrahan Babacan, Merve Nur Acar Tayyar, Mehmet Can Şahin, Selma Şengiz Erhan, Müge Öner Tamam
Journal: Clinical Nuclear Medicine (2024)

Abstract Extranodal lymphomas without lymph node involvement are rarely observed and create diagnostic challenges. We present the case of a 33-year-old woman who was admitted with abdominal swelling. Ultrasonography findings suggested bilateral ovarian masses. 18 F-FDG PET/CT revealed intense uptake on the bilateral pelvic mass and thyroid gland. Following excisional surgery and thyroid fine-needle aspiration biopsy, the patient was diagnosed with diffuse large B-cell lymphoma. This case is exceptionally rare, as it presents 2 synchronous extranodal involvements in the ovaries and the thyroid gland independently while not presenting any lymph node activity, which has not been reported before.
Exploring Theranostic Avenues in Adrenocortical Carcinoma Using Chemokine Receptor and Prostate-Specific Membrane Antigen–Directed PET/CT
Authors: Stefanie Hahner, Takahiro Higuchi, Sebastian E. Serfling, Samuel Samnick, Carmina Teresa Fuss, Britta Heinze, Andreas K. Buck, Andreas Schirbel, Martin Fassnacht, Rudolf A. Werner
Journal: Clinical Nuclear Medicine (2024)

Abstract We report on an adrenocortical carcinoma (ACC) patient, which has exhausted previous treatment options and was scheduled for prostate-specific membrane antigen (PSMA)- and C-X-C motif chemokine receptor 4 (CXCR4)-targeted PET/CT. We identified PSMA-avid pulmonary metastases exhibiting modest radiotracer accumulation, while chemokine receptor PET/CT provided intense uptake. This dual-tracer molecular imaging approach revealed that chemokine receptor PET appears to be more suitable in patients with advanced ACC, indicating that CXCR4-directed radioligand therapy may be considered in such patients suffering from end-stage disease. Given its dismal prognosis, chemokine receptor-directed theranostics may therefore extend the therapeutic armamentarium as last-line option in advanced ACC.
Mitral Annular Calcification as a Potential False-Positive for Cardiac Amyloidosis in 99mTc-DPD Scintigraphy Accurately Identified by SPECT/CT
Authors: Ana Rita Pereira Nunes, Victor Manuel Alves
Journal: Clinical Nuclear Medicine (2024)

Abstract 99m Tc-PYP/DPD/HDMP cardiac scintigraphy has a pivotal role in the diagnosis of ATTR cardiac amyloidosis. The combined findings of a Perugini visual score of 2 or 3 in the scan and the absence of monoclonal proteins in blood and urine are highly specific for the diagnosis of ATTR cardiac amyloidosis without a tissue biopsy. We report a case of mitral annular and valve calcification accurately identified in the SPECT/CT, but which could be misinterpreted as ATTR cardiac amyloidosis if only acquiring planar and SPECT images.
Identifying Mixed Dementia With Lewy Bodies and Alzheimer Disease Using Multitracer PET Imaging
Authors: Qijun Li, Junshan Wang, Ruixue Cui, Jing Yuan
Journal: Clinical Nuclear Medicine (2024)

Abstract We reported imaging findings with complex signs that were corresponded with both dementia with Lewy bodies (DLB) and Alzheimer disease (AD) in the case of a 78-year-old woman. Initially suspected as DLB due to cognitive and movement issues, diagnostic support included the cingulate island sign on 18 F-FDG PET, positive 131 I-MIBG cardiac scintigraphy, and DAT PET. However, MRI indicated hippocampal atrophy, and 18 F-FDG PET showed hypometabolism in the medial temporal lobe, suggesting the possibility of concomitant AD. Subsequent detection of β-amyloid pathology and tau accumulation in the brain further supported the concurrent presence of AD pathology.
Gastroesophageal Reflux Revealed by 18F-MFBG PET/CT
Authors: Jian He, Liqing Yang, Limeng He, Wei Zhang, Lu Guo
Journal: Clinical Nuclear Medicine (2024)

Abstract A 56-year-old woman who had a lung transplant 4 months ago presented frequent vomiting for 1 month. Barium meal and 99m Tc gastroesophageal scintigraphy showed no gastroesophageal reflux. The patient was enrolled in a clinical trial and underwent 18 F-MFBG PET/CT dynamic imaging. At the seventh minute of dynamic imaging, the images revealed reflux from the cardia into the esophagus and reached the oral cavity.
Comparative Study of Different Imaging Modalities for Diagnosis of Bone Metastases of Prostate Cancer
Authors: Keunyoung Kim, Mihyang Ha, Seong-Jang Kim
Journal: Clinical Nuclear Medicine (2024)

Purpose This study aimed to compare the diagnostic performances of 8 different imaging modalities for preoperative detection of bone metastases in prostate cancer patients by performing a network meta-analysis using direct comparison studies with 2 or more imaging techniques. Patients and Methods We searched PubMed, Embase, and Cochrane Library for studies evaluating the performances of 8 different imaging modalities for the preoperative detection of bone metastases in prostate cancer patients. The network meta-analysis was performed in patient-based analysis. The consistency was evaluated by examining the agreement between direct and indirect treatment effects, and the surface under the cumulative ranking curve (SUCRA) values were obtained to calculate the probability of each imaging modality being the most effective diagnostic method. Results A total of 999 patients from 13 direct comparison studies using 8 different imaging modalities for preoperative detection or follow-up of bone metastases in prostate cancer patients were included. For the detection of bone metastases of prostate cancer, 68 Ga-PSMA-11 PET/CT showed the highest SUCRA values of sensitivity, positive predictive value, accuracy, and diagnostic odds ratio. In addition, 18 F-NaF PET/CT and SPECT/CT showed high SUCRA values. Conclusions 68 Ga-PSMA-11 PET/CT showed the highest SUCRA values. Other imaging modalities showed complementary diagnostic roles for preoperative detection of bone metastases in patients with prostate cancer, except bone scintigraphy and MRI.
68Ga-Pentixafor PET/CT for In Vivo Imaging of CXCR4 Receptors in Glioma Demonstrating a Potential for Response Assessment to Radiochemotherapy: Preliminary Results
Authors: Abdul Waheed, Baljinder Singh, Ankit Watts, Harneet Kaur, Harmandeep Singh, Kirti Dhingra, Chirag Ahuja, Renu Madan, Apinderpreet Singh, Bishan D. Radotra
Journal: Clinical Nuclear Medicine (2024)

Purpose The aim of this study was to evaluate the diagnostic potential of 68 Ga-pentixafor PET/CT for in vivo CXCR4 receptors imaging in glioma and its possible role in response assessment to radiochemotherapy (R-CT). Methods Nineteen (12 men, 7 women) patients with glioblastoma multiforme (GBM) underwent 68 Ga-pentixafor PET/CT, contrast-enhanced MR, and MR spectroscopy. Patients were divided in to 2 groups, that is, group I was the presurgical (n = 9) group in which the scanning was done before surgery, and PET findings were correlated with CXCR4 receptors’ density. The group II was the postsurgical (n = 10) group in which the scanning was done before and after R-CT and used for treatment response evaluation. The quantitative analysis of 68 Ga-pentixafor PET/CT evaluated the mean SUV max , SUV mean , SUV peak , and T/B values. MR spectroscopy data evaluated the ratios of tumor metabolites (choline, NAA, creatine). Results 68 Ga-Pentixafor uptake was noted in all (n = 19) the patients. In the group I, the mean SUV max , SUV mean , SUV peak , and T/B values were found to be 4.5 ± 1.6, 0.60 ± 0.26, 1.95 ± 0.8, and 6.9 ± 4.6, respectively. A significant correlation ( P &lt; 0.005) was found between SUV mean and choline/NAA ratio. Immunohistochemistry performed in 7/9 showed CXCR4 receptors’ positivity (intensity 3 + ; stained cells &gt;50.0%). In the group II, the mean SUV max at baseline was 4.6 ± 2.1 and did not differ (4.4 ± 1.6) significantly from the value noted at post–R-CT follow-up PET/CT imaging. At 6 months’ clinical follow-up, 4 patients showed stable disease. SUV max and T/B ratios at follow-up imaging were lower (3.70 ± 0.90, 2.64 ± 1.35) than the corresponding values (4.40 ± 2.8; 2.91 ± 0.93) noted at baseline. Six (6/10) patients showed disease progression, and the mean SUV max , and T/B ratio in these patients were significantly ( P &lt; 0.05) higher than the corresponding values at baseline and also higher than that noted in the stable patients. Conclusions 68 Ga-Pentixafor PET/CT can be used for in vivo mapping of CXCR4 receptors in GBM. The technique after validation in a large cohort of patients may have added diagnostic value for the early detection of GBM recurrence and for treatment response evaluation.
Pulmonary Mucoepidermoid Carcinoma Mimicking Carcinoid Lung on 18F-FDG and 68Ga-DOTANOC PET/CT
Authors: Jasim Jaleel, Nishikant Avinash Damle, Aditi Khurana, Mohit Joshi, Deepali Jain
Journal: Clinical Nuclear Medicine (2024)

Abstract Pulmonary mucoepidermoid carcinoma (PMEC) is a rare pulmonary neoplasm. Although 18 F-FDG PET/CT has been shown to present with increased metabolic activity in PMEC, literature does not report increased somatostatin receptor expression in these tumors. We present the case of a 15-year-old boy where PMEC mimicked a typical carcinoid of the lung on DOTANOC PET/CT by showing significant uptake on 68 Ga-DOTANOC.
Aneurysmal 99mTc-HMPAO Uptake in Brain Death
Authors: Danka Do, Petr Suhaj, Jiri Benes, Radoslav Matej, Otto Lang
Journal: Clinical Nuclear Medicine (2024)

Abstract A 41-year-old man was admitted to hospital due to sudden loss of consciousness. A regional brain perfusion SPECT/low-dose CT showed abnormal 99m Tc-HMPAO uptake in the right hemisphere frontotemporally without any other supratentorial or infratentorial radiotracer uptake. A neuropathological examination disclosed a middle cerebral artery aneurysm. Presumably, vessel wall fibrosis prevented collapse. Multiple transmural dissections of the fibrotic aneurysmal wall were the source of the subarachnoid hemorrhage. This interesting image shows that radiotracer accumulation in cerebral artery aneurysms can be a diagnostic pitfall in brain death scintigraphy assessment.
Granulomatosis With Polyangiitis of Spinal Dura Presenting With “Bottle Brush Sign” on 18F-FDG PET/CT
Authors: Yue Zhang, Chunyan Wu, Qinwen Shi, Minggang Su
Journal: Clinical Nuclear Medicine (2024)

Abstract A 72-year-old man with fever and weakness in both lower limbs underwent thoracolumbar MRI and 18 F-FDG PET/CT. The PET/CT scan revealed diffused FDG uptake along the spinal dura mater from T7 to S2 level like a “bottle brush.” Pathologic examination after biopsy of spinal canal lesions manifested granulomatous inflammation. The blood test showed cytoplasmic antineutrophil cytoplasmic antibody (ANCA) and myeloperoxidase-ANCAs were positive, whereas the perinuclear ANCA was negative. Eventually, he was diagnosed with granulomatosis with polyangiitis.