bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diabetic myonecrosis complicated by emphysematous pyomyositis and abscess caused by Escherichia coli: a case report
Authors: Kerola Anne M. , Eklund Kari K. , Valleala Heikki , Tynninen Olli , Helve Jaakko , Haapamäki Ville , Eriksson Mari 
Published: July 2024

Abstract
Background
Necrotizing myopathies and muscle necrosis can be caused by immune-mediated mechanisms, drugs, ischemia, and infections, and differential diagnosis may be challenging.

Case presentation
We describe a case of diabetic myonecrosis complicated by pyomyositis and abscess caused by Escherichia coli. A white woman in her late forties was admitted to the hospital with a 1.5 week history of bilateral swelling, weakness, and mild pain of the lower extremities and inability to walk. She had a history of type 1 diabetes complicated by diabetic retinopathy, neuropathy, nephropathy, and end-stage renal disease. C-reactive protein was 203 mg/l, while creatinine kinase was only mildly elevated to 700 IU/l. Magnetic resonance imaging of her lower limb muscles showed extensive edema, and muscle biopsy was suggestive of necrotizing myopathy with mild inflammation. No myositis-associated or myositis-specific antibodies were detected. Initially, she was suspected to have seronegative immune-mediated necrotizing myopathy, but later her condition was considered to be explained better by diabetic myonecrosis with multifocal involvement. Her symptoms alleviated without any immunosuppressive treatment. After a month, she developed new-onset and more severe symptoms in her right posterior thigh. She was diagnosed with emphysematous urinary tract infection and emphysematous myositis and abscess of the right hamstring muscle. Bacterial cultures of drained pus from abscess and urine were positive for Escherichia coli. In addition to abscess drainage, she received two 3–4-week courses of intravenous antibiotics. In the discussion, we compare the symptoms and findings typically found in pyomyositis, immune-mediated necrotizing myopathy, and diabetic myonecrosis (spontaneous ischemic necrosis of skeletal muscle among people with diabetes). All of these diseases may cause muscle weakness and pain, muscle edema in imaging, and muscle necrosis. However, many differences exist in their clinical presentation, imaging, histology, and extramuscular symptoms, which can be useful in determining diagnosis. As pyomyositis often occurs in muscles with pre-existing pathologies, the ischemic muscle has likely served as a favorable breeding ground for the E. coli in our case.

Conclusions
Identifying the etiology of necrotizing myopathy is a diagnostic challenge and often requires a multidisciplinary assessment of internists, pathologists, and radiologists. Moreover, the presence of two rare conditions concomitantly is possible in cases with atypical features.
Modulation of gut microbiota composition and predicted metabolic capacity after nutritional programming with a plant-rich diet in Atlantic salmon (Salmo salar): insights across developmental stages
Authors: Tawfik Marwa Mamdouh , Lorgen-Ritchie Marlene , Król Elżbieta , McMillan Stuart , Norambuena Fernando , Bolnick Daniel I. , Douglas Alex , Tocher Douglas R , Betancor Mónica B. , Martin Samuel A. M. 
Published: July 2024

AbstractTo promote sustainable aquaculture, the formulation of Atlantic salmon (Salmo salar) feeds has changed in recent decades, focusing on replacing standard marine-based ingredients with plant-based alternatives, increasingly demonstrating successful outcomes in terms of fish performance. However, little is known about how these plant-based diets may impact the gut microbiota at first feeding and onwards. Nutritional programming (NP) is one strategy applied for exposing fish to a plant-based (V) diet at an early stage in life to promote full utilisation of plant-based ingredients and prevent potential adverse impacts of exposure to a plant-rich diet later in life. We investigated the impact of NP on gut microbiota by introducing fish to plant ingredients (V fish) during first feeding for a brief period of two weeks (stimulus phase) and compared those to fish fed a marine-based diet (M fish). Results demonstrated that V fish not only maintained growth performance at 16 (intermediate phase) and 22 (challenge phase) weeks post first feeding (wpff) when compared to M fish but also modulated gut microbiota. PERMANOVA general effects revealed gut microbiota dissimilarity by fish group (V vs. M fish) and phases (stimulus vs. intermediate vs. challenge). However, no interaction effect of both groups and phases was demonstrated, suggesting a sustained impact of V diet (nutritional history) on fish across time points/phases. Moreover, the V diet exerted a significant cumulative modulatory effect on the Atlantic salmon gut microbiota at 16 wpff that was not demonstrated at two wpff, although both fish groups were fed the M diet at 16 wpff. The nutritional history/dietary regime is the main NP influencing factor, whereas environmental and host factors significantly impacted microbiota composition in M fish. Microbial metabolic reactions of amino acid metabolism were higher in M fish when compared to V fish at two wpff suggesting microbiota played a role in digesting the essential amino acids of M feed. The excessive mucin O-degradation revealed in V fish at two wpff was mitigated in later life stages after NP, suggesting physiological adaptability and tolerance to V diet. Future studies are required to explore more fully how the microbiota functionally contributes to the NP.
Integrated preparation and manipulation of high-dimensional flying structured photons
Authors: Zhao Haoqi , Zhang Yichi , Gao Zihe , Yim Jieun , Wu Shuang , Litchinitser Natalia M. , Ge Li , Feng Liang 
Published: July 2024

AbstractThe hope for a futuristic global quantum internet that provides robust and high-capacity quantum information transfer lies largely on qudits, the fundamental quantum information carriers prepared in high-dimensional superposition states. However, preparing and manipulating N-dimensional flying qudits as well as subsequently establishing their entanglement are still challenging tasks, which require precise and simultaneous maneuver of 2 (N-1) parameters across multiple degrees of freedom. Here, using an integrated approach, we explore the synergy from two degrees of freedom of light, spatial mode and polarization, to generate, encode, and manipulate flying structured photons and their formed qudits in a four-dimensional Hilbert space with high quantum fidelity, intrinsically enabling enhanced noise resilience and higher quantum data rates. The four eigen spin–orbit modes of our qudits possess identical spatial–temporal characteristics in terms of intensity distribution and group velocity, thereby preserving long-haul coherence within the entirety of the quantum data transmission link. Judiciously leveraging the bi-photon entanglement, which is well preserved in the integrated manipulation process, we present versatile spin–orbit cluster states in an extensive dimensional Hilbert space. Such cluster states hold the promise for quantum error correction which can further bolster the channel robustness in long-range quantum communication.
2023 Korean Society of Echocardiography position paper for the diagnosis and management of valvular heart disease, part II: mitral and tricuspid valve disease
Authors: Shim Chi Young , Kim Eun Kyoung , Cho Dong-Hyuk , Park Jun-Bean , Seo Jeong-Sook , Son Jung-Woo , Kim In-Cheol , Lee Sang-Hyun , Heo Ran , Lee Hyun-Jung , Lee Sahmin , Sun Byung Joo , Yoon Se-Jung , Lee Sun Hwa , Kim Hyung Yoon , Kim Hyue Mee , Park Jae-Hyeong , Hong Geu-Ru , Jung Hae Ok , Kim Yong-Jin , Kim Kye Hun , Kang Duk-Hyun , Ha Jong-Won , Kim Hyungseop , Chung Wook-Jin , Park Chan Seok , Ahn Hyo-Suk , Chung Woo-Baek , Cho Eun Joo , Cho Jung Sun , Ryu Dong Ryeol , Yang Dong Heon , Park Jeong Rang , Kim Woo-Shik , Sohn Il Suk , Na Jin Oh , Park Seong-Mi , Hwang Sun Ho , Choi Ji-Yong , Park Tae-Ho , Park Yong Hyun , Choi Jung Hyun , Kim Hack-Lyoung , Seo Hye Sun , Park Jin-Sun , Choi Eui-Young , Son Jang-Won , Kim Shin-Jae , Rhee Sang Jae , Cho In-Jeong , Byun Young Sup , Shin Sung-Hee , Lee Sun Hwa , Beom Jong Wook , Lee Ju-Hee , Bae Dae-Hwan , Kim Sung-Ai , Park Dae Gyun , Kang Min-Kyung , Hong Kyung-Soon ,   The Korean Valve Survey Investigators
Published: July 2024

AbstractThis manuscript represents the official position of the Korean Society of Echocardiography on valvular heart diseases. This position paper focuses on the diagnosis and management of valvular heart diseases with referring to the guidelines recently published by the American College of Cardiology/American Heart Association and the European Society of Cardiology. The committee sought to reflect national data on the topic of valvular heart diseases published to date through a systematic literature search based on validity and relevance. In the part II of this article, we intend to present recommendations for diagnosis and treatment of mitral valve disease and tricuspid valve disease.
Expression of the receptor tyrosine kinase AXL and clinical outcomes to cabozantinib and everolimus in patients with metastatic renal cell carcinoma enrolled in the METEOR trial.
Authors: Nabil Laimon Yasmin , Paul Morgan , Ghandour Fatme , El Ahmar Nourhan , Matar Sayed , Denize Thomas , Bagheri Sheshdeh Aseman , Savla Varunika , Mohanna Razan Assaad , Sun Maxine , Saliby Renee Maria , Saad Eddy , Machaalani Marc , Braun David A. , Aftab Dana T. , Xie Wanling , CHOUEIRI Toni K. , Signoretti Sabina 
Published: July 2024

4543 Background: High expression of the receptor tyrosine kinase AXL has been associated with resistance to targeted agents and anti-PD-1 therapy in multiple tumor types, including metastatic clear cell Renal Cell Carcinoma (mccRCC). Cabozantinib (cabo), a multitargeted tyrosine kinase inhibitor (TKI) active against VEGFR, MET, and AXL, is approved for the treatment of mccRCC, but no predictive biomarkers are available. Here, we analyzed tumor samples from the METEOR trial to assess whether AXL expression predicts improved clinical outcomes with cabo relative to everolimus (evero, mTOR inhibitor) in patients (pts) with mccRCC. Methods: Double immunohistochemistry staining for AXL and CD45/CD163 (immune cell/ macrophage markers) was performed on 278 pretreatment tumor tissues from the METEOR trial (cabo=147; evero=131). Image analysis algorithms were used to assess the % of AXL+ tumor cells (TC), % of AXL+ immune cells (IC), and combined % of AXL+ TC and IC (TC/IC). Optimal cutoffs, based on the minimum p-value approach, were determined at the 17th, 30th, and 22nd percentile for TC, IC, and TC/IC, respectively. The association with progression-free survival (PFS) was assessed using Cox regression adjusted for IMDC risk groups, the presence of bone metastases, and the number of previous VEGFR TKI treatments. The association with objective response rate (ORR) (cabo arm only due to low response rate in evero arm) was reported descriptively. Results: We observed a strong correlation between % AXL+ TC and % AXL+ IC (Spearman correlation coefficient 0.85; p-value <0.001). In the evero arm, high % AXL+ TC and high % AXL+ TC/IC were significantly associated with shorter PFS (median 1.9 vs. 4.1 months and 1.9 vs 4.2 months, respectively); a similar trend was observed for % AXL+ IC. In the cabo arm, % AXL+ TC, % AXL+ IC, and % AXL+ TC/IC were not associated with PFS or ORR (Table). The magnitude of increase in PFS for pts receiving cabo versus evero was larger in pts with high % AXL+ TC compared to pts with low % AXL+ TC (HR: 0.30 vs. 0.51, p-interaction=0.18) and in pts with high % AXL+ TC/IC compared to pts with low % AXL+ TC/IC (HR: 0.30 vs 0.53, p-interaction=0.12). Conclusions: Our finding that the improvement in outcome with cabo relative to evero is more evident in pts with high levels of AXL expression supports that the antitumor activity of cabo in mccRCC is mediated, in part, by AXL inhibition. Our work identifies AXL expression as a potential predictive biomarker for cabo-based therapies in mccRCC. [Table: see text]
Molecular analysis of the HCRN GU16-260-Cohort A phase II study of first-line (1L) nivolumab (nivo) and salvage nivo + ipilimumab (ipi) in patients (pts) with advanced clear cell renal cell carcinoma (accRCC).
Authors: Zaemes Jacob Peter , Hugaboom Miya , Shah Valisha , Haas Naomi B. , McDermott David F. , Jegede Opeyemi , Bilen Mehmet Asim , Stein Mark N. , Sosman Jeffrey A. , Alter Robert S. , Plimack Elizabeth R. , Hurwitz Michael E. , Wu Catherine J. , Einstein David Johnson , Hammers Hans J. , Signoretti Sabina , West Destiny , Denize Thomas , Atkins Michael B. , Braun David A. 
Published: July 2024

4546 Background: Seven molecular subsets of ccRCC have been proposed: 1: Angiogenic/Stromal; 2: Angiogenic; 3: Complement/Ω-oxidation; 4: T-effector/Proliferative; 5: Proliferative; 6: Stromal/Proliferative; and 7: snoRNA (Motzer et al. Can Cell 2020). In an analysis of IMmotion 151, which compared 1L atezolizumab/bevacizumab to sunitinib, combination immune checkpoint blockade (ICB) and anti-VEGF therapy was associated with improved progression-free survival (PFS) and overall survival (OS) in clusters (CLs) 4 and 5, increased PFS in CL 7, and decreased OS in CL 2 (Motzer Can Cell 2020, Motzer JAMA Onc 2022). CL 4 was also associated with higher PFS and objective response rate (ORR) in >1L nivo compared to everolimus in an analysis of CheckMate-025 (Denize CCR 2022). To date, outcomes have not been compared among accRCC subtypes in pts who received 1L pure ICB. Methods: In HCRN GU16-260-Cohort A, pts with accRCC received 1L nivo monotherapy until progressive disease (PD), unacceptable toxicity, or completion of 96 weeks of therapy. Pre-treatment FFPE tumor samples were obtained. A machine learning model (random forest) was trained on annotated transcriptomic data from bulk RNA-seq and used to classify tumors that passed quality control into one of the 7 molecular subtypes. Results: 70 tumor samples contained adequate RNA quality and were classified as outlined in the table. IMDC rates and ORR (40%) for the RNAseq population closely matched those of the whole study (Atkins JCO 2022). No tumors were classified in CL 7 and only 3 in CL 5. Tumors in each IMDC group contained a mix of subtypes. The highest ORR occurred in CL 4 (6/10, 60.0%); CL 4 median PFS was 15.2 months and 1-year PFS was 60%. ORR was also high in CLs 1 and 3 at 52.4% and 40.0%, respectively and lowest in CL 2 (12.5%). PD as best response (5/10, 50.0%) and short PFS (5.1 months) were seen in CL 6. Conclusions: Consistent with prior analyses with combination ICB + anti-VEGF and >1L ICB, CL 4 was associated with robust 1L ICB monotherapy antitumor efficacy. Surprisingly, ORR was also high in CLs 1 and 3. In this small dataset, transcriptomic signatures enriched for but did not fully predict ORR. Future prospective trials are needed to identify more discriminative biomarkers of efficacy for pure ICB therapy.[Table: see text]
A pilot study of tazemetostat and pembrolizumab in advanced urothelial carcinoma (ETCTN 10183).
Authors: Hussain Maha H. A. , Kocherginsky Masha , Singh Parminder , Tan Winston , Myint Zin , Jiang Di (Maria) , Wulff-Burchfield Elizabeth Marie , Ma Yangruijue , Sharon Elad , Piekarz Richard , Meeks Joshua J , VanderWeele David James 
Published: July 2024

4574 Background: Mutations of COMPASS-related proteins KMT2D, KMT2C, and KDM6A are observed in 66% of advanced urothelial carcinomas (UC). In vivo, the administration of tazemetostat, an enzymatic EZH2 inhibitor (EZH2i), reduced tumor burden and enhanced the immune response in animal models of UC. We hypothesized that tazemetostat might improve response to immunotherapy in advanced UC. Methods: ETCTN 10183 (NCT03854474) is a multicenter pilot study evaluating the safety and efficacy of tazemetostat 800 mg BID+ pembrolizumab 200 mg given every three weeks for up to two years in patients (pts) with platinum-refractory (Arm A) or cisplatin/chemo-ineligible advanced UC (Arm B). The primary objective was to identify the recommended phase two dose (RP2D) of tazemetostat in combination with pembrolizumab. Secondary objectives included safety, response rate, and progression-free survival. Translational objectives included determining tumor mutational burden in COMPASS-related genes, tumor subtyping, TCR clonality, T cell infiltration, and PDL-1 expression. Results: There were no dose-limiting toxicities in the safety lead-in phase (n=6 pts), and the RP2D for tazemetostat was established at 800 mg BID. Baseline characteristics for Arm A N=12, Arm B N=13: 72% males; 96% white, 4% Black; 88% ECOG PS 0-1; 88% had bladder primary, 20% Stage III, 72% stage IV; 80% had visceral or bone metastases. The median number of cycles was 5 in Arm A (range 1-35) and 4 in Arm B (range 2-12). Treatment related G3/4 adverse events (AEs) were observed in 8 patients, most common were anemia and lymphopenia (n=2 each). Treatment related G1/2 AEs included nausea (n=6); skin and subcutaneous tissue disorders (n=3); anemia, lymphopenia, and thrombocytopenia (n=2 each). Among evaluable patients (n=10 in each arm), partial response rate was: Arm A 30%, Arm B 20%; stable disease: Arm A 30%, Arm B 30%; and progressive disease: Arm A 30%, Arm B 20%. 8 pts were on study treatment for ≥ 9 cycles (5 in Arm A, 3 in Arm B). All pts are off protocol treatment. Median progression-free survival was 3.06 (95% CI: 1.38-7.75) months for Arm A and 3.02 (95%CI: 2.4-5.65) for Arm B. Conclusions: Tazemetostat 800 mg BID and pembrolizumab combination is feasible and well-tolerated in patients with advanced UC. In this pilot study, improvement in efficacy relative to historical controls of pembrolizumab alone appears to be modest. Response in tumors with COMPASS-related mutations and EZH2 activity will be evaluated. Clinical trial information: NCT03854474 .
SOGUG-Vexillum: Phase II non-randomized clinical trial of nivolumab/ipilimumab maintenance following first-line chemotherapy in unresectable locally advanced or metastatic urothelial cancer.
Authors: de Velasco Guillermo , García Carbonero Iciar , Anido Urbano , Virizuela Juan Antonio , Álvarez-Fernández Carlos , Álvarez-Márquez Francisco José , Justo de la Peña Marina , Lozano Rebeca , Gajate Pablo , Reig Oscar , Iranzo Aina , Pujol Eduardo 
Published: July 2024

4576 Background: Nivolumab (nivo) 1mg/kg plus ipilimumab (ipi) 3mg/kg achieved the highest ORR (42.4%) in refractory metastatic urothelial carcinoma (mUC) with a manageable safety profile. The addition of nivo and ipi subsequently to first-line chemotherapy (CT) could consolidate the clinical benefit. Methods: This single arm, open-label, multicenter study evaluates the effectiveness of ipi 3 mg/kg and nivo 1 mg/kg (Q3W) for 4 cycles followed by nivo maintenance therapy (Q4W) in delaying disease progression in patients with unresectable urothelial cancer that did not progress after first-line platinum-based CT (at least 4-6 cycles of CT). Autoimmune disease, immune deficiency, and symptomatic brain metastasis were excluded. The primary endpoint is Progression Free Survival (PFS) in intention-to-treat and PD-L1 populations. Secondary endpoints include: objective response rate (ORR), duration of response (DoR), overall survival (OS), overall survival from 1st dose of CT (cOS), progression-free survival from 1st dose of CT (cPFS), safety and translational biomarker analysis. Sample size was estimated using a Simon II stage design for 4-months PFS rate (H0= 40%; H1= 60; α= 0.05; β= 80%; attrition 10%), requiring 25 patients in the 1st stage and up to 66 in total. Here we report the interim analysis for 1st stage. Results: As of January 2024, the 1st accrual stage was completed with 25 evaluable patients. Baseline characteristics are outlined in the table. With a median follow-up of 6.8 months (95% CI: 6.2-10.5), the 4-m PFS rate was 64% (95% CI: 47.7-85.9) and the median PFS was 4.3 months (95% CI: 3.2-NR). The median cPFS was 9.4 months (95% CI: 8-NR). The 6-m OS rate was 76.4% (95% CI: 60-97.2), while median cOS was 15.4 months (95% CI: 15.4-NR). The median duration of treatment was 2.6 months (95% CI: 2.1, 5.7). Nivo and ipi were permanently discontinued due to toxicity in 3 (12%) and 1 (4.2%) patients, respectively. Nivo doses were delayed in 8 (32%) patients and ipi in 3 (12%) for management of toxicity. Grade ≥3 toxicities were reported in 8 (32%) patients, being the most common: Immune-mediated hepatitis (8%), ALT/AST increased (8%) and diarrhea (8%). Conclusions: Maintenance treatment with nivo and ipi showed preliminary efficacy consolidating clinical benefit to CT with a manageable safety profile. The 4-m PFS rate surpassed the futility threshold in the interim analysis and the accrual in Stage II is underway. Final survival results are awaited. Clinical trial information: NCT05219435 . [Table: see text]
Randomized Phase II Trial of Immunotherapy-Based Total Neoadjuvant Therapy for Proficient Mismatch Repair or Microsatellite Stable Locally Advanced Rectal Cancer (TORCH)
Authors: Xia Fan , Wang Yaqi , Wang Hui , Shen Lijun , Xiang Zuolin , Zhao Yutian , Zhang Huojun , Wan Juefeng , Zhang Hui , Wang Yan , Wu Ruiyan , Wang Jingwen , Yang Wang , Zhou Menglong , Zhou Shujuan , Chen Yajie , Zhang Zhiyuan , Wu Xian , Xuan Yan , Wang Renjie , Sun Yiqun , Tong Tong , Zhang Xun , Wang Lei , Huang Dan , Sheng Weiqi , Yan Hao , Yang Xu , Shen Yuxin , Xu Yu , Zhao Ruping , Mo Miao , Cai Guoxiang , Cai Sanjun , Xu Ye , Zhang Zhen 
Published: July 2024

PURPOSE
To assess whether the integration of PD-1 inhibitor with total neoadjuvant therapy (iTNT) can lead to an improvement in complete responses (CRs) and favors a watch-and-wait (WW) strategy in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC).

PATIENTS AND METHODS
We conducted a prospective, multicenter, randomized, open-label, phase II trial using a pick-the-winner design. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma were randomly assigned to group A for short-course radiotherapy (SCRT) followed by six cycles of consolidation immunochemotherapy with capecitabine and oxaliplatin and toripalimab or to group B for two cycles of induction immunochemotherapy followed by SCRT and the rest four doses. Either total mesorectal excision or WW was applied on the basis of tumor response. The primary end point was CR which included pathological CR (pCR) after surgery and clinical CR (cCR) if WW was applicable, with hypothesis of an increased CR of 40% after iTNT compared with historical data of 25% after conventional TNT.

RESULTS

Of the 130 patients enrolled, 121 pMMR/MSS patients were evaluable (62 in group A and 59 in group B). At a median follow-up of 19 months, CR was achieved at 56.5% in group A and 54.2% in group B. Both groups fulfilled the predefined statistical hypothesis (
P
< .001). Both groups reported a pCR rate of 50%. Respectively, 15 patients in each group underwent WW and remained disease free. The most frequent grade 3 to 4 toxicities were thrombocytopenia and neutropenia. Patients in group A had higher rate of cCR (43.5%
v
35.6%) at restaging and lower rate of grade 3 to 4 thrombocytopenia (24.2%
v
33.9%) during neoadjuvant treatment.

CONCLUSION
The iTNT regimens remarkably improved CR rates in pMMR/MSS LARC compared with historical benchmark with acceptable toxicity. Up-front SCRT followed by immunochemotherapy was selected for future definitive study.