tbuckley/cabot-search huggingface dataset:
Phase I/II Investigator-Initiated Study of Olaparib and Temozolomide in SCLC: Final Analysis and CNS Outcomes
Authors: Catherine B. Meador, Subba R. Digumarthy, Beow Y. Yeap, Yin P. Hung, Mari Mino-Kenudson, Anna F. Farago, Rebecca S. Heist, J. Paul Marcoux, Deepa Rangachari, David A. Barbie, Zofia Piotrowska
Journal: Clinical Cancer Research (2024)

Temozolomide plus PARP inhibition has shown promise in small cell lung cancer (SCLC). We previously reported outcomes from the first 50 patients (cohort 1) of a phase I/II trial of olaparib/temozolomide in recurrent SCLC. In this study, we report a final analysis of this trial, including a second cohort with an alternate dosing strategy and an exploratory analysis of central nervous system (CNS)-specific outcomes.
Fecal microbiota transplantation against moderate‐to‐severe atopic dermatitis: A randomized, double‐blind controlled explorer trial
Authors: Xiaochun Liu, Yang Luo, Xingyu Chen, Mingyang Wu, Xiaoqiang Xu, Jingru Tian, Yingxia Gao, Jun Zhu, Zhifeng Wang, Yuan Zhou, Yu Zhang, Xiaokai Wang, Wei Li, Qianjin Lu, Xu Yao
Journal: Allergy (2024)

Abstract Background Fecal microbiota transplantation (FMT) is a novel treatment for inflammatory diseases. Herein, we assess its safety, efficacy, and immunological impact in patients with moderate‐to‐severe atopic dermatitis (AD). Methods In this randomized, double‐blind, placebo‐controlled clinical trial, we performed the efficacy and safety assessment of FMT for moderate‐to‐severe adult patients with AD. All patients received FMT or placebo once a week for 3 weeks, in addition to their standard background treatments. Patients underwent disease severity assessments at weeks 0, 1, 2, 4, 8, 12, and 16, and blood and fecal samples were collected for immunologic analysis and metagenomic shotgun sequencing, respectively. Safety was monitored throughout the trial. Results Improvements in eczema area and severity index (EASI) scores and percentage of patients achieving EASI 50 (50% reduction in EASI score) were greater in patients treated with FMT than in placebo‐treated patients. No serious adverse reactions occurred during the trial. FMT treatment decreased the Th2 and Th17 cell proportions among the peripheral blood mononuclear cells, and the levels of TNF‐α, and total IgE in serum. By contrast, the expression levels of IL‐12p70 and perforin on NK cells were increased. Moreover, FMT altered the abundance of species and functional pathways of the gut microbiota in the patients, especially the abundance of Megamonas funiformis and the pathway for 1,4‐dihydroxy‐6‐naphthoate biosynthesis II. Conclusion FMT was a safe and effective therapy in moderate‐to‐severe adult patients with AD; the treatment changed the gut microbiota compositions and functions.
IMPA1-derived inositol maintains stemness in castration-resistant prostate cancer via IMPDH2 activation
Authors: Che-Chia Hsu, Guihua Wang, Chien-Feng Li, Xian Zhang, Zhen Cai, Tingjin Chen, Bo-Syong Pan, Rajesh Kumar Manne, Gagan Deep, Haiwei Gu, Yuzhuo Wang, Danni Peng, Vasudevarao Penugurti, Xiaobo Zhou, Zhigang Xu, Zhongzhu Chen, Ming Chen, Andrew J. Armstrong, Jiaoti Huang, Hong-Yu Li, Hui-Kuan Lin
Journal: The Journal of Experimental Medicine (2024)

Acquisition of prostate cancer stem cells (PCSCs) manifested during androgen ablation therapy (ABT) contributes to castration-resistant prostate cancer (CRPC). However, little is known about the specific metabolites critically orchestrating this process. Here, we show that IMPA1-derived inositol enriched in PCSCs is a key metabolite crucially maintaining PCSCs for CRPC progression and ABT resistance. Notably, conditional Impa1 knockout in the prostate abrogates the pool and properties of PCSCs to orchestrate CRPC progression and prolong the survival of TRAMP mice. IMPA1-derived inositol serves as a cofactor that directly binds to and activates IMPDH2, which synthesizes guanylate nucleotides for maintaining PCSCs with ARlow/- features leading to CRPC progression and ABT resistance. IMPA1/inositol/IMPDH2 axis is upregulated in human prostate cancer, and its overexpression predicts poor survival outcomes. Genetically and pharmacologically targeting the IMPA1/inositol/IMPDH2 axis abrogates CRPC and overcomes ABT resistance in various CRPC xenografts, patient-derived xenograft (PDX) tumor models, and TRAMP mouse models. Our study identifies IMPDH2 as an inositol sensor whose activation by inositol represents a key mechanism for maintaining PCSCs for CRPC and ABT resistance.
Prognosis and Risks for Probable Chronic Lung Allograft Dysfunction: A Prospective Multicenter Study
Authors: Jamie L. Todd, S. Sam Weigt, Megan L Neely, Maria V. Grau-Sepulveda, Kristen Mason, Michelle L. Sever, Karen Kesler, Jerry Kirchner, Courtney W. Frankel, Tereza Martinu, Michael Y Shino, Annette M Jackson, Elizabeth N. Pavlisko, Nikki Williams, Mark A. Robien, Lianne G. Singer, Marie Budev, Wayne Tsuang, Pali D. Shah, John M. Reynolds, Laurie D Snyder, John A Belperio, Scott M. Palmer
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Rationale: Chronic lung allograft dysfunction (CLAD) hinders lung transplant success. A 2019 consensus refined CLAD diagnosis, introducing probable or definite CLAD based on persistence of lung function decline. Outcomes and risks for probable CLAD remain uncertain. Objectives: We sought to determine the prognosis and clinical risks for probable CLAD in a prospective multicenter cohort. Methods: Clinical Trials in Organ Transplantation-20 included 745 CLAD-eligible adult lung recipients at five centers and applied rigorous methods to prospectively adjudicate probable CLAD. The impact of probable CLAD on graft loss was determined using a Cox model that considered CLAD as a time-dependent covariate. Regularized Cox modeling with least absolute shrinkage and selection operator (LASSO) penalty was used to evaluate donor or recipient characteristics and the occurrence and timing of posttransplant events as probable CLAD risks. Similar analyses were performed for definite CLAD. Measurements and Main Results: Probable CLAD occurred in 29.7% of patients at 3 years posttransplant and conferred a marked increase in risk for graft loss (unadjusted hazard ratio = 4.38, P < 0.001). Most patients (80%) with probable CLAD progressed to definite CLAD. Cytomegalovirus infection and, specifically, late presence (>90 d posttransplant) of donor-specific alloantibodies, acute rejection, acute lung injury, or organizing pneumonia contributed the greatest independent information about probable CLAD risk. Definite CLAD risks were similar. Conclusions: Probable CLAD identifies patients at high risk for graft loss, supporting prospective identification of this condition for early initiation of CLAD-directed interventions. More effective strategies to prevent posttransplant cytomegalovirus, inhibit allospecific immunity, and reduce tissue injury are needed to reduce probable CLAD and improve lung recipient survival. Clinical trial registered with www.clinicaltrials.gov (NCT02631720).
Evidence that autoantibody production may be driven by acute Epstein-Barr virus infection in Sjögren’s disease
Authors: Erin Hudson, Lijun Yang, Elizabeth K Chu, Haoyang Zhuang, Rawad Daniel Arja, Blas Y Betancourt, Indraneel Bhattacharyya, Shuhong Han, Seunghee Cha, Edward K L Chan, Mathew Sebastian, Carolyn Stalvey, Marvin J Fritzler, Westley H Reeves
Journal: Annals of the Rheumatic Diseases (2024)

Sjögren's disease (SD) is an autoimmune disease affecting the exocrine glands that is associated with autoantibodies against Ro60/SS-A, anti-Ro52/TRIM21, La/SS-B and others. We examined the role of acute Epstein-Barr virus (EBV) infection in the pathogenesis of these autoantibodies in a previously healthy patient (patient 1) with primary EBV infection who developed SD with anti-Ro/La and anti-Smith/U1 ribonucleoprotein (Sm/U1RNP) autoantibodies and had lymphoplasmacytic foci on labial salivary gland biopsy.
Laboratory-Confirmed Influenza-Associated Hospitalizations Among Children and Adults — Influenza Hospitalization Surveillance Network, United States, 2010–2023
Authors: Angelle Naquin, Alissa O’Halloran, Dawud Ujamaa, Devi Sundaresan, Svetlana Masalovich, Charisse N. Cummings, Kameela Noah, Seema Jain, Pam Daily Kirley, Nisha B. Alden, Elizabeth Austin, James Meek, Kimberly Yousey-Hindes, Kyle Openo, Lucy Witt, Maya L. Monroe, Justin Henderson, Val Tellez Nunez, Ruth Lynfield, Melissa McMahon, Yomei P. Shaw, Caroline McCahon, Nancy Spina, Kerianne Engesser, Brenda L. Tesini, Maria A. Gaitan, Eli Shiltz, Krista Lung, Melissa Sutton, M. Andraya Hendrick, William Schaffner, H. Keipp Talbot, Andrea George, Hafsa Zahid, Carrie Reed, Shikha Garg, Catherine H. Bozio
Journal: MMWR Surveillance Summaries (2024)

Seasonal influenza accounts for 9.3 million-41 million illnesses, 100,000-710,000 hospitalizations, and 4,900-51,000 deaths annually in the United States. Since 2003, the Influenza Hospitalization Surveillance Network (FluSurv-NET) has been conducting population-based surveillance for laboratory-confirmed influenza-associated hospitalizations in the United States, including weekly rate estimations and descriptions of clinical characteristics and outcomes for hospitalized patients. However, a comprehensive summary of trends in hospitalization rates and clinical data collected from the surveillance platform has not been available.
Airway Mucus Plugs on Chest Computed Tomography Are Associated with Exacerbations in COPD
Authors: Emily Wan, Andrew Yen, Rim Elalami, Scott Grumley, Hrudaya P. Nath, Wei Wang, Sharon Brouha, Padma P. Manapragada, Mostafa Abozeed, Muhammad Usman Aziz, Mohd Zahid, Asmaa N Ahmed, Nina L. Terry, Pietro Nardelli, James C Ross, Victor Kim, Sushilkumar Sonavane, Seth J Kligerman, Jørgen Vestbo, Alvar Agusti, Kangjin Kim, Raul San José Estépar, Edwin K Silverman, Michael H Cho, Alejandro A Diaz
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Rationale/Objective: Acute exacerbations (AEs) of chronic obstructive pulmonary disease (COPD) are associated with significant morbidity and mortality. Whether mucus plugs are associated with prospective exacerbations has not been examined extensively.
Comparison of two strategies of glucocorticoid withdrawal in patients with rheumatoid arthritis in low disease activity (STAR): a randomised, placebo-controlled, double-blind trial
Authors: Adeline Ruyssen-Witrand, Clara Brusq, Maëva Masson, Vanina Bongard, Carine Salliot, Lucile Poiroux, Minh Nguyen, Christian Hubert Roux, Christophe Richez, Alain Saraux, Pascale Vergne-Salle, Jacques Morel, René-Marc Flipo, Muriel Piperno, Jacques-Eric Gottenberg, Hubert Marotte, Martin Soubrier, Laure Gossec, Philippe Dieudé, Slim Lassoued, Laurent Zabraniecki, Guillaume Couture, Jean Frédéric Boyer, Bénédicte Jamard, Yannick Degboe, Arnaud Constantin
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Objectives</h3> To compare two strategies—a hydrocortisone replacement strategy and a prednisone tapering strategy—for their success in glucocorticoid discontinuation in patients with rheumatoid arthritis (RA) with low disease activity (LDA). <h3>Methods</h3> The Strategies for glucocorticoid TApering in Rheumatoid arthritis (STAR) study was a double-blind, double-placebo randomised controlled trial including patients with RA receiving a stable dose of glucocorticoid 5 mg/day for ≥3 months and were in LDA for ≥3 months. Patients were randomly assigned in a 1:1 ratio to either replace prednisone with 20 mg/day of hydrocortisone for 3 months, then reduce to 10 mg/day for 3 months before discontinuation or to taper prednisone by 1 mg/day every month until complete discontinuation, contingent on maintaining LDA. The primary outcome was the percentage of patients achieving glucocorticoid discontinuation at 12 months. Other secondary outcomes were proportion of flares, need for additional glucocorticoid use, disease activity, patient-reported outcomes and the results of adrenocorticotropic hormone (ACTH) stimulation tests. <h3>Results</h3> Of the 102 patients randomised in the trial (mean age 62.4 years, 70.6% females), 53 had hydrocortisone replacement and 49 tapered prednisone. At 12 months, 29 patients (55%) in the hydrocortisone replacement group and 23 patients (47%) in the prednisone tapering group achieved glucocorticoid discontinuation (p=0.4). No difference was observed between groups in the secondary outcomes. No cases of acute adrenal insufficiency were observed; however, 17 patients still had an abnormal ACTH stimulation test at 12 months, with no differences between arms. <h3>Conclusion</h3> A hydrocortisone replacement strategy was not superior to a prednisone tapering strategy for achieving glucocorticoid discontinuation success in patients with RA in LDA. <h3>Trial registration number</h3> NCT02997605.
Pre-treatment metastatic biopsy: a step towards precision oncology for urothelial cancer
Authors: Niklas Klümper, Alexander Cox, Gottfrid Sjödahl, Florian Roghmann, Christian Bolenz, Arndt Hartmann, Viktor Grünwald, Bishoy M. Faltas, Michael Hölzel, Markus Eckstein
Journal: Nature Reviews Urology (2024)
CTR-FAPI PET enables precision management of medullary thyroid carcinoma
Authors: Ziren Kong, Zhu Li, Xi-Yang Cui, Jian Wang, Mengxin Xu, Yang Liu, Junyi Chen, Song Ni, Zongmin Zhang, Xiaowei Fan, Jiazhao Huang, Yansong Lin, Yuning Sun, Yuqin He, Xinfeng Lin, Tianyu Meng, Han Li, Yixuan Song, Boshizhang Peng, Changming An, Chenyan Gao, Nan Li, Chen Liu, Yiming Zhu, Zhi Yang, Zhibo Liu, Shaoyan Liu
Journal: Cancer Discovery (2024)

Abstract Medullary thyroid carcinoma (MTC) can only be cured through the excision of all metastatic lesions, but current clinical practice fails to localize the disease in 29% to 60% of patients. Previously, we developed a fibroblast activation protein inhibitor (FAPI)-based covalent targeted radioligand (CTR) for improved detection sensitivity and accuracy. In this first-in-class clinical trial, we head-to-head compared [68Ga]Ga-CTR-FAPI PET-CT and [18F]fluorodeoxyglucose ([18F]FDG) PET-CT in 50 patients with MTC. The primary endpoint was the patient-based detection rate, with [68Ga]Ga-CTR-FAPI exhibiting higher detection than [18F]FDG (98% vs. 66%, P = 0.0002). This improved detection was attributed to increased tumor uptake (maximum standardized uptake value = 11.71 ± 9.16 vs. 2.55 ± 1.73, P &amp;lt; 0.0001). Diagnostic accuracy, validated on lesions with gold-standard pathology, was greater for [68Ga]Ga-CTR-FAPI compared with [18F]FDG (96.7% vs. 43.3%, P &amp;lt; 0.0001). Notably, the management of 32% of patients was altered following [68Ga]Ga-CTR-FAPI PET-CT, and the surgical plan was changed for 66.7% of patients. Overall, [68Ga]Ga-CTR-FAPI PET-CT provided superior detection and diagnostic accuracy compared with [18F]FDG PET-CT, enabling precision management of patients with MTC. Significance: In this first-in-class clinical trial of CTR, [68Ga]Ga-CTR-FAPI demonstrated an improved patient-based detection rate (98%), tumor uptake (maximum standardized uptake value = 11.71 ± 9.16), and pathology-validated diagnostic accuracy (96.7%) compared with the currently approved method in MTC treatment. It directly altered management in 32% of patients, enabling precision diagnosis and management of MTC. See related commentary by Witney, p. 264
Non-tuberculosis Mycobacterial Lung Infection from the Position of Computed Tomography (Clinical Observation)
Authors: T. G. Morozova, A. I. Kunin
Journal: Radiology - Practice (2024)

Mycobacterioses are caused by a large number of conditionally pathogenic mycobacteria that are widespread in the environment. The incidence of diseases caused by nontuberculosis mycobacteria (NTMB) is steadily increasing due to an increase in the number of immunoscompromised patients. The aim of the study was to analyze controversial issues encountered in the differential diagnosis of tuberculosis and non-tuberculosis mycobacterial infection. Materials and methods . The study was performed on a 64–slice GE REVOLUTION EVO computed tomograph. Discussion. Based on the anamnesis and the results of a microbiological study, the attending physician eventually diagnosed a non-tuberculosis mycobacterial infection and prescribed appropriate treatment. Conclusion. Despite the fact that in most cases the radiological and clinical picture of non-tuberculosis mycobacteriosis is nonspecific, there are clinical and radiological syndromes highly specific for non-tuberculosis mycobacteriosis.
The Severity of Myelopathy as a Diagnostic and Prognostic Indicator in the Treatment of Patients with Cervical Spinal Stenosis
Authors: A. A. Sufianov, D. N. Nabiev, K. A. Diachkov, A. V. Burtsev, R. A. Sufianov, M. T. Karsanova
Journal: Radiology - Practice (2024)

Cervical spinal stenosis is accompanied by dysfunction of the spinal cord, leading to numerous complications and disability of patients. These issues are well known to radiologists, vertebrologists, and neurosurgeons, however, not all of multiple diagnostic problems and issues of surgical treatment can be considered resolved. Purpose of the study . Justification of the possibilities and necessity of qualitative and quantitative MRI study of the severity of myelopathy in cervical spinal stenosis. Materials and methods. The results of an MRI examination of 82 patients with cervical spinal stenosis due to degenerative processes were carried out with the use of osteoplastic bilateral laminoplasty technique with simultaneous foraminotomy under neurophysiological control. The examination was conducted before and after the treatment. The study was carried out using standard programs, such as T2 haste localizer, t2_tse_cor_p2, t2_tse_sag_p2, t1_tse_sag_p2. Results . The focus of myelopathy was detected by MRI in 74.4 % of cases, which confirmed the severity of the pathology. 28 out of 60 patients with myelopathy displayed a clearly defined «snakeeyes» sign, also knows as «owl-eyes» or «fried-eggs» appearance. In some patients, one zone was identified in the form of a rounded focus of increased signal intensity on the axial section. The average value of the signal intensity coefficient in patients before treatment was 1.89 ± 0.31, after treatment — 1.63 ± 0.21. Significant differences in MRI before and after treatment occurred in 45 % of patients. Conclusion. The results of the work showed that quantitative assessment of the signal intensity from the spinal cord in stenosis can be used to assess the severity of myelopathy and compare data before and after treatment. In order to identify the source of the most intense signal more accurately and increase the overall measurement accuracy, it is advisable to carry out color mapping of images.
Features of Vascularization of the Transitional Zone of the Uterus in Patients with Chronic Nonspecific Endometritis
Authors: A. V. Pomortsev, E. A. Kuzmenko, N. N. Kuzmenko, Yu. Yu. Dyachenko, S. M. Avakyan
Journal: Radiology - Practice (2024)

Aim. Тo study the peculiarities of blood supply to the transitional zone of the uterus in patients with chronic nonspecific endometritis (ChE). Materials and methods . 106 women aged 22–45 years were examined. The main group included 72 patients with morphologically verified chronic endometritis. We distinguished subgroup I (n = 39.37%) of HE with an autoimmune component, subgroup II (n = 33.31%) with HE without an autoimmune component, as well as a control group consisting of 34 patients with a normal result of morphological examination. Transabdominal and transvaginal ultrasound examination (ultrasound) of the uterus and appendages was performed on the 18th–23rd day of the cycle, with the calculation of the parameter proposed by US — the coefficient of vascularization of the transitional zone of the uterus (k). Outcomes. In the control group, the average k value was 32 ± 2.6%, in the subgroup of patients with an autoimmune component (subgroup I) — 17.0 ± 4.0%, in the subgroup with a nonimmune component (subgroup II) — 23.0 ± 3.4%. Statistically significant differences in the k value were obtained between subgroup I and all the others, but there were no differences between subgroup II and the control group. Autoimmune nonspecific HE was predicted when the vascularization coefficient was below 20.9%. In nonimmune nonspecific HE, the resulting model was not statistically significant. Nonimmune nonspecific HE was predicted when the vascularization coefficient was equal to or higher than 18.6%. Under normal conditions, the resulting model was statistically significant. The norm was predicted when the vascularization coefficient was equal to or higher than 27.6%. Conclusion. The proposed coefficient of vascularization of the transitional zone of the uterus (k) showed high diagnostic value in patients with nonspecific СhE and it can be recommended for inclusion in the ultrasound examination protocol at the stage of pre-gravidar preparation.
Ovarial Torsion in Young Children. Ultrasound Diagnostic
Authors: E. B. Olkhova, V. O. Soboleva, O. V. Tolkach
Journal: Radiology - Practice (2024)

Background. Early adnexal torsion (AT) is extremely rare. It usually involves a torsion of the ovary together with the tube, which cannot be differentiated by transabdominal ultrasound, so the terms "adnexal torsion" and "ovarian torsion" for children are echographically identical. Objective. To study the features of echographic representation of ovarian torsion in infant girls. Materials and Methods . During 2015–2024, adnexal torsion was echographically diagnosed in 6 girls of the first year of life. All patients underwent transabdominal ultrasound in B-mode and color Doppler scanning. All children were operated, and the diagnosis was verified. Results. The frequency of adnexal torsion in children under 1 year of age was 13.3% of all patients (45) with this pathology. The complaints and clinical picture were nonspecific. In all cases, suspicion of adnexal torsion was expressed only when ultrasound was performed. There was an increase in the volume of the affected ovary by 6.91 ± 0.68 times compared to the contralateral ovary and increased echogenicity of the ovarian parenchyma, against which numerous anechogenic follicles were traced. Vascular pattern in the parenchyma of the affected ovary was detected in 2/6 cases (33.33%), uterine appendages were irreversibly changed. Hyperstimulated ovaries were observed in 4 out of 6 cases. The distribution of follicles in the affected ovary was chaotic, there was no "necklace symptom", there was no marked rounding of the ovarian shape, and the amount of stromal component in the tilted ovary was relatively small. In 5/6 (83.3%) girls, no pelvic cavity effusion was noted. Conclusion There are no specific anamnestic and clinical data suggestive of adnexal torsion in infants, which determines the importance of ultrasound as virtually the only method of emergency diagnosis of this pathology. The peculiarity of ultrasound in the infant should be the maximum expansion of the area of examination with attempts to visualize the pelvic organs regardless of the degree of bladder filling. The basis of echographic diagnosis of adnexal torsion in infants are structural changes of the appendage in B-mode: increase in linear size of 1.5–2 times, volume of 4–10 times and increased echogenicity of the stroma. Rounding of the shape of the affected ovary is insignificant. A feature of twisted appendage in infants is a large number of follicles in the affected ovary (2/3 of observations). The "necklace" symptom is atypical. The presence of abdominal effusion in adnexal torsion in infants is not characteristic. Preservation of the vascular pattern in the ovary does not exclude adnexal torsion, is infrequent (in 1/3 of cases) and does not guarantee preservation of ovarian viability.