bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atypical gouty tophus masquerading as a foreign body granuloma
Authors: Omar Farhana , Nor Hashimah Abu Mansor Matardiah , Suhaila Ab Wahab , Mohammad Mohaidin Farhana , Raymond Azman Ali 
Published: August 2024

AbstractSubcutaneous nodular lesions in a patient with significantly elevated inflammatory markers always raise the possibility of infectious diagnoses such as atypical infection, pyogenic abscess, mycobacterial infection, and malignancy. Definitive diagnosis requires tissue biopsy and histopathologic examination. The atypical presentation of a foreign body granuloma with concurrent intraoperative findings supports the diagnosis of gouty arthritis.We report a case of a 67-year-old man who presented with an inflammatory nodular lesion on the left elbow that was initially suspected to have an infectious cause. Histopathologic examination of the nodular tissue later revealed that the patient had a foreign body granuloma due to urate crystal deposition. The atypical appearance of the gouty arthritis, the low serum urate level, the negative crystal identification in the synovial fluid, and the markedly elevated inflammatory markers, which did not respond to the previous antibiotic and steroid therapy, raised the suspicion of atypical infection in this case.
Post COVID-19 persistent symptoms and functional status in COVID-19 survivors: a multi-center study
Authors: Goda Amal Mahmoud Ibrahim , Ahmed Osama Amin Abd Elhamid , Wedn Ahmed Moustafa Abdel Samad , Manzour Ayat F. 
Published: August 2024

Abstract
Background
Post COVID symptoms are a series of chronic symptoms that patients may experience after resolution of acute COVID-19. Different post-COVID-19 condition phenotypes might exist, although exact causes, management, and outcomes are not known.

Aim
To assess the functional status among post-COVID-19 survivors and identify the associated socio-demographic, clinical, and laboratory risk factors of the poor functional status among those cases and to identify the most common persistent symptoms among post-COVID-19 survivors after discharge. This was a cross-sectional study conducted on 150 recovered cases who had been infected with COVID-19 as confirmed by swab during hospitalization and being interviewed regarding functional status 6 months post-hospital discharge. Cases were divided into two groups: the decreased functional status group (n = 74) and the non-decreased functional status group (n = 76).

Results
The present study indicated statistically significant differences between the studied groups; receiving the influenza vaccine was significantly associated with keeping the pre-COVID functional status (p = 0.02). The reduced functional status group had a significantly more severe disease course, prolonged hospital as well as ICU stay (p < 0.001), and worse CT findings than the normal functional status group (p = 0.004). Long-term symptoms such as headache, mood changes, insomnia, hearing problems, dry eyes, breathlessness, and chest tightness were significantly more prevalent among those who reported limitations in their functional status (p < 0.001). There were significantly higher CRP, serum ferritin, and D-dimer in the reduced functional status group.

Conclusion
The present study highlights that most COVID-19 recovered cases have different degrees of functional limitations ranging from null to severe based on the PCFS scale. These limitations were affected by periodic influenza vaccination, ICU admission, and length of hospital stay. Some laboratory parameters were associated with reduced functionality: CRP, D-dimer, and serum ferritin. Psychological/neurological symptoms and breathlessness were significantly associated with reduced PCFS. This calls for public health action and necessitates widespread health education of post-COVID-19 health consequences.
Empathy-related abnormalities among women with premenstrual dysphoric disorder: clinical and functional magnetic resonance imaging study
Authors: Lerner Yulia , Raz Gal , Bloch Miki , Krasnoshtein Michael , Tevet Michal , Hendler Talma , Tene Oren 
Published: August 2024

Background
Empathy refers to the cognitive and emotional reactions of an individual to the experiences of another. Women with premenstrual dysphoric disorder (PMDD) report severe social difficulties during the luteal phase of their menstrual cycle.

Aims
This clinical and functional magnetic resonance imaging study aimed to explore affective and cognitive empathy in women with PMDD, during the highly symptomatic luteal phase.

Method
Overall, 32 women with PMDD and 20 healthy controls participated in the study. The neuroimaging data were collected using a highly empathy-engaging movie. First, we characterised the synchrony of neural responses within PMDD and healthy groups, using the inter-individual correlation approach. Next, using network cohesion analysis, we compared connectivity within and between brain networks associated with affective and cognitive empathy between groups, and assessed the association of these network patterns with empathic measures.

Results
A consistent, although complex, picture of empathy abnormalities was found. Patients with PMDD showed decreased neural synchrony in parietal and frontal key nodes of cognitive empathy processing (theory-of-mind network), but higher neural synchrony in the anterior insula and anterior cingulate cortex, a part of the salience network, implicated in affective empathy. Positive correlations between cognitive perspective-taking scores and neural synchrony were found within the theory-of-mind network. Interestingly, during highly emotional moments, the PMDD group showed increased functional connectivity within this network.

Conclusions
Similar to major depression, individuals with PMDD show enhanced affective empathy and reduced cognitive empathy. These findings echo clinical observations reported when women with PMDD have a dysregulated emotional response to negative stimuli.
ACE-Breast-02: A pivotal phase II/III trial of ARX788, a novel anti-HER2 antibody-drug conjugate (ADC), versus lapatinib plus capecitabine for HER2+ advanced breast cancer (ABC).
Authors: Hu Xichun , Wang Leiping , Zhang Jian , Zhang Qingyuan , Ouyang Quchang , Wang Xiaojia , Li Wei , Xie Weimin , Tong Zhongsheng , Xu Faliang , Liu Wei , Wang Shushen , Sun Tao 
Published: August 2024

1020 Background: ARX788 is a next-generation ADC of HER2 monoclonal antibody site-specifically conjugated with Amberstatin 269, a potent cytotoxic tubulin inhibitor. Here we report the interim result from this seamless phase II/III trial in patients who progressed on trastuzumab based therapy. Methods: This randomized study was conducted in HER2+ (FISH+ or IHC3+) ABC in 85 centers in China. Patients with unresectable or metastatic breast cancer pretreated with trastuzumab and taxane were randomized 1:1 to receive ARX788 (1.5mg/kg, IV, Q3W) or lapatinib plus capecitabine (LC, lapatinib 1250mg, QD; capecitabine 1000mg/m2 BID, d1-14, Q3W), stratified by previous chemotherapy lines (0-1 vs. >1) and visceral metastasis (yes vs. no). ARX788 was not pre-medicated with any prophylactic measures. Primary endpoint was progress-free survival (PFS) determined by Independent Review Committee (IRC). Results: As of Dec. 21, 2022, 221 patients were randomly assigned to ARX788 and 220 to LC, and 240 PFS events occurred. Efficacy results are listed in table 1. The median PFS was 11.33 months with ARX788 versus 8.25 months with LC as per IRC (HR 0.64, p=0.0006). Treatment-related adverse events (TRAEs) of any grade occurred in 98.6% (217/220) and 99.1% (213/215) of patients, respectively. TRAEs of grade 3-5 was similar in two groups (41.4% and 40.0%, respectively), commonest being blurred vision (12.3%), dry eye (9.1%), keratopathy (5.9%) and interstitial lung disease (5.9%) with ARX788 and hand-foot syndrome (18.1%), hypokalemia (5.1%), diarrhea (4.2%) with LC. 71 patients (32.3%) had interstitial lung disease with ARX788, primarily grade 1 or 2 (26.8%) with 3 (1.4%) possibly having drug-related deaths. 164 patients (74.5%) had ocular events related to ARX788, primarily grade 1 or 2 (55.5%) with no grade 4 or 5. Conclusions: ARX788 significantly prolonged PFS comparing to LC in patients with HER2+ ABC previously treated with trastuzumab and taxane. While ocular toxicity and interstitial lung disease were common and manageable, its hematological and GI toxicities under no prophylactic premedication compared favorably with already available ADCs. Clinical trial information: CTR20201708. [Table: see text]
Maintenance treatment with toripalimab and anlotinib after anthracycline-based chemotherapy in patients with advanced soft tissue sarcoma (TORAN): A single-arm, phase 2 trial.
Authors: Deng Yaotiao , Liu Jie , Li Mei , Jiang Yu 
Published: August 2024

11572 Background: In patients with advanced soft tissue sarcoma (STS) who have achieved disease control after anthracycline-based chemotherapy, maintenance therapy is being explored. This study evaluated the efficacy and safety of toripalimab (a monoclonal antibody against the programmed cell death-1 receptor) combined with anlotinib (a multitargeted tyrosine kinase inhibitor) as a maintenance treatment. Methods: Patients with advanced STS who have achieved disease control after at least four cycles of first-line anthracycline-based chemotherapy were enrolled in this single-arm, phase 2 trial. Fifty patients are planned to receive treatment with toripalimab and anlotinib. The primary endpoint was progression-free survival rate at 24 weeks (PFR24w) during maintenance therapy. Secondary endpoints were median progression-free survival (PFS), median overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Results: By the cut-off date of Jan 25, 2024, 22 patients were enrolled, including patients with leiomyosarcoma (n =5), synovial sarcoma (n =3), epithelioid sarcoma (n =3), dedifferentiated liposarcoma (n =2) and other different subtypes of sarcomas (n =9). The median follow-up time was 11 months. Response has been evaluated in 18 patients. The ORR and DCR were 22.2% and 100%. The PFR24w was 67%, the median PFS was 11.8 months, and the median OS was not reached. The grade 3 or higher adverse events were hypertension (n =4), hemorrhage (n =1), adrenal insufficiency (n =1) and hypertriglyceridemia (n =1). Conclusions: Maintenance therapy with toripalimab and anlotinib is a promising treatment option for patients with advanced STS after first-line anthracycline-based chemotherapy. Clinical trial information: ChiCTR2100054901.
Adjuvant S-1 vs. observation for resected biliary tract cancer: 5-year follow-up of the JCOG1202/ASCOT.
Authors: Nakachi Kohei , Ikeda Masafumi , Konishi Masaru , Mizusawa Junki , Katayama Hiroshi , Sano Yusuke , Uesaka Katsuhiko , Yanagimoto Hiroaki , Morinaga Soichiro , Wada Hiroshi , Shimada Kazuaki , Takahashi Yu , Nakagori Toshio , Gotoh Kunihito , Kamata Ken , Shimizu Yasuhiro , Ishii Hiroshi , Okusaka Takuji , Furuse Junji , Ueno Makoto 
Published: August 2024

4119 Background: S-1, an oral fluoropyrimidine derivative, demonstrated significant improvement in overall survival (OS) over observation in patients with curatively resected biliary tract cancer (BTC) (hazard ratio [HR] 0.694, p=0.008; the 3-year OS, 67.6% vs. 77.1%, Lancet 2023). We present updated efficacy data based on a 5-year follow-up of JCOG1202/ASCOT. Methods: Patients aged 20-80 years who had histologically confirmed extrahepatic cholangiocarcinoma, gallbladder carcinoma, ampullary carcinoma, or intrahepatic cholangiocarcinoma in a resected specimen and had undergone R0/R1 resection were randomly assigned (1:1) to undergo observation or to receive S-1 (at the dose of 40 mg/m2 twice daily for 4 weeks, followed by 2 weeks of rest, for 4 cycles). The primary endpoint was OS, and the secondary endpoints were relapse-free survival (RFS), adverse events, and proportion of treatment completion. Results: From September 2013 to June 2018, a total of 440 patients (observation, n=222; adjuvant S-1, n=218) were enrolled. The final data cutoff date was June 23, 2023, and the median follow-up duration was 61.5 months. Of all the randomized patients, 215 (48.4%) had died (118 [53.2%] in the observation group; 97 [44.5%] in the S-1 group). The 5-year OS was 52.2% in the observation group and 64.1% in the S-1 group (stratified HR 0.723, 95% confidence interval [CI], 0.551-0.948; one-sided p=0.019). Of the 440 patients, 239 (54.3%) had RFS event (127 [57.2%] in the observation group; 112 [51.4%] in the S-1 group). The 5-year RFS was 45.9% in the observation group and 53.6% in the S-1 group (unstratified HR 0.797, 95% CI 0.618-1.028, stratified HR 0.761, 95% CI 0.589-0.984 in the sensitivity analysis). Most prespecified subgroup analyses (age, primary site, stage, lymph node metastases, types of resections, and serum CA19-9 levels) revealed favorable OS and RFS for the S-1 group. Conclusions: Adjuvant S-1 therapy maintained its survival benefit in a 5-year long-term follow-up, with clinically meaningful improvement in RFS, suggesting that it could be a standard of care for BTC. Clinical trial information: UMIN000011688.
A phase 2 study of trifluridine/tipiracil (FTD/TPI) in recurrent/metastatic nasopharyngeal (r/m NPC) carcinomas with or without prior exposure to fluoropyrimidines.
Authors: Low Jia Li , Chong Wan Qin , Hui Edwin Pun , Lai Winky , Le Candice , Sooi Kenneth , Walsh Robert John , Chan Anthony T. C. , Goh Boon C. , Ma Brigette 
Published: August 2024

6032 Background: Despite effective local treatment, up to 30% of patients with nasopharyngeal carcinoma (NPC) relapse and require systemic treatment. There are limited therapeutic options beyond cisplatin, gemcitabine and immunotherapy and the median survival of r/m disease is about 20 months. Capecitabine, a fluoropyrimidine, has shown some efficacy with a median time to progression of 4.9 months in heavily pretreated r/m NPC but there is a need for alternative treatments. FTD/TPI is an oral drug combination of trifluridine and tipiracil, a thymidine phosphorylase inhibitor preventing rapid degradation of trifluridine, thus increasing its exposure. It has shown activity in colorectal, gastric and breast cancers despite prior fluoropyrimidines. This study explores the efficacy and safety of FTD/TPI in r/m NPC, with or without prior exposure to fluoropyrimidines. Methods: In this single-arm phase II trial, patients were administered oral FTD/TPI twice daily at 35mg/m2 on days 1-5 and 8-12 of a 28-day cycle. The primary endpoint was disease control rate (DCR) at 12 weeks, with secondary endpoints including progression-free survival (PFS), overall response rate (ORR), safety, and tolerability. Results: A total of 33 patients were recruited. Median age was 56 years (range: 34-82), most were males (n=27, 82%), with median of 3 (range: 1-12) prior lines of treatment in the metastatic setting. Approximately half (48.5%) received prior fluoropyrimidines. DCR at 12 weeks was 63.6%, with an ORR of 18.2%. DCR was 68.8% and 58.8% in patients with and without prior fluoropyrimidine exposure respectively. Median PFS was 6.5 months (95% CI 2.8-10.2) and overall survival was 13.1 months (95% CI 7.1-19.2). FTD/TPI demonstrated a manageable safety profile, with most common treatment-related adverse events of neutropenia, anaemia, fatigue, nausea and anorexia. 60% of patients required dose modifications, most commonly due to neutropenia, that could be overcome by dose reduction or prolongation to 5-weekly cycles. 1 patient required discontinuation due to anaemia resulting in syncope. Conclusions: FTD/TPI is well tolerated, compares favorably to Capecitabine and showed promising anti-tumor activity with meaningful clinical benefit regardless of prior exposure to fluoropyrimidines. This oral chemotherapy offers an attractive choice for patients valuing quality of life, minimizing hospital visits and resource utilization such as chemotherapy infusions. Further investigations in randomized studies are warranted. Clinical trial information: NCT04627961 .
Treatment discontinuation due to toxicity for patients with acute myeloid leukemia (AML) treated on SWOG S1203.
Authors: Raychaudhuri Suravi , Othus Megan , Percival Mary-Elizabeth M. , Garcia-Manero Guillermo , Appelbaum Frederick R. , Erba Harry Paul , Appelbaum Jacob 
Published: August 2024

6529 Background: Curative-intent therapy for patients with newly diagnosed AML centers on the use of cytarabine as part of an intensive multi-drug induction regimen. Treatment-related toxicity may lead to patients stopping treatment, despite the considerable risk of inadequately treated AML. We compared rates of protocol therapy discontinuation due to adverse events (AEs) in either of two standard induction regimens (7+3 or high dose cytarabine + idarubicin, IA) on the S1203 study (Garcia-Manero; Leukemia 2023). Methods: S1203 was a randomized study of patients <60 years old with newly diagnosed AML. Patients were required to have performance status (PS) <3, ejection fraction >45%, and no prolonged QTc interval or known cardiac disease. There were no exclusion criteria for kidney or liver function. On the 7+3 induction arm, subjects received daunorubicin 90 mg/m2 IV daily days 1-3 with continuous infusion cytarabine 100 mg/m2 daily days 1-7. On the IA arm, subjects received idarubicin 12 mg/m2 daily days 1-3 with continuous infusion cytarabine 1.5 g/m2 daily days 1-4. Toxicities were assessed per the Common Terminology Criteria for Adverse Events version 4.0. Rates of discontinuation were compared using Fisher’s exact test. Results: From 4/2013-11/2015, 522 subjects were randomized (261 to each arm). Treatment discontinuation due to either death or toxicity occurred in 8 vs 22 patients on 7+3 vs IA respectively (p=0.014). During induction, 0 patients on the 7+3 arm discontinued treatment due to toxicity versus 4 patients on the IA arm (0% vs 2%; p=0.12). Toxicities leading to treatment discontinuation on the IA arm included congestive heart failure (n=2, one with concurrent arrhythmia), acute kidney injury (n=1), and hypotension complicated by stroke and cardiac arrest (n=1). Two of the 4 patients who discontinued treatment due to toxicity on IA achieved a complete remission after their first cycle. For patients with PS 2-3 (n=40 on 7+3, n=27 on IA), rates of grade 3-5 AEs were 85% vs 86% and rates of grade 5 AEs were 0% vs 11% (p=0.065). Conclusions: 7+3 was well tolerated. Excluding patients from S1203 with PS 2-3 or decreased hepatic/renal function would not have prevented treatment-related toxicity. The low rate of protocol therapy discontinuation due to toxicity suggests that eligibility criteria for clinical trials could be further broadened to improve patient access. Clinical trial information: NCT0180233 . [Table: see text]
Preliminary efficacy and safety of total neoadjuvant therapy combined with PD-L1 blockade in pMMR/MSS locally advanced rectal cancer (ESTIMATE): A prospective, single-arm, phase II trial.
Authors: Zhang Xuan , Feng Qing , Cai Xinyi , Yu Kun , Shen Tao , Pan Dingguo , Tan Jing , Ju Yunhe , Zhang Lijuan , Xie Lin , Dong Jianhua , Xia Cuifeng , Xiong Wei , Yang Quan , Wu Tao , Li Yun-Feng 
Published: August 2024

e15602 Background: Patients with locally advanced rectal cancer (LARC) experience benefits from total neoadjuvant therapy (TNT). This study aims to explore the efficacy and safety of combining TNT with immunotherapy for pMMR/MSS LARC patients. Methods: ESTIMATE is a prospective, single-center, phase II study (ChiCTR2400079718) enrolling pMMR/MSS LARC patients with tumors located 10cm away from the anal margin. Treatment involved induction chemotherapy with immunotherapy ([mFOLFOX6, days 1-2 + Envafolimab 200mg, ih, day 1]; q2w; 2 cycles), long-course concurrent chemoradiotherapy (LCRT) with immunotherapy ([IMRT, 50Gy/25f, 2Gy + Cape 825mg/m2, bid]; 5w + Envafolimab 200mg, ih, day 1; q2w; 3 cycles), consolidation chemotherapy with immunotherapy ([mFOLFOX6 + Envafolimab; 2 cycles), and then total mesorectal excision (TME) 3 weeks later or watch and wait (W&W). The primary endpoint is the pathological complete response (pCR) rate. Results: Until Nov. 16th, 2023, 35 patients were enrolled, with 28 completing the TNT regimen. The efficacy analysis revealed that out of 28 patients, 12 (42.9%) achieved clinical complete response (cCR), with 7 individuals choosing the W&W strategy. 21 patients underwent TME, yielding 8 with a tumor regression grade (TRG) of 0, 7 with TRG of 1, and 6 with TRG of 2. The rates of pCR, major pathological response (MPR), and complete response (CR) were 38.1% (8/21), 71.4% (15/21), and 53.6% (15/28), respectively. 25 (89.3%) patients experienced treatment-related adverse events (AEs) of any grade. Non-hematological AEs included decreased appetite, fatigue, nausea, and vomiting, while hematological AEs mainly comprised thrombocytopenia, anemia, and leukopenia or neutrophilia. Grade III AEs were primarily leukopenia or neutrophilia (2/28, 7.1%). Additionally, circulating tumor DNA (ctDNA) levels were measured in 7 patients who chose the W&W strategy after achieving cCR. Of these, 6 tested negative for minimal residual disease (MRD), while 1 had a positive MRD result (ctDNA: 0.56 MTM/ml). As of Jan. 26th, 2024, with a median follow-up of 5 months (range: 3-6), no recurrence was observed in any of the patients. Conclusions: The TNT approach, integrating LCRT with mFOLFOX6 and PD-L1 blockade, demonstrated a favorable CR rate and acceptable tolerability, offering a potential avenue for organ preservation in low rectal cancer patients with pMMR/MSS. Long-term benefits need validation through further follow-up. Clinical trial information: ChiCTR2400079718. [Table: see text]