tbuckley/cabot-search huggingface dataset:
Investigating L1CAM and β-catenin as prognostic indicators in fertility-sparing endometrial cancer treatment.
Authors: Jeong-Yeol Park, Ok-Ju Kang, Uiree Jo
Journal: Journal of Clinical Oncology (2024)

e17582 Background: Fertility-sparing progestin therapy is well-known treatment option for young women with endometrium-confined, low-grade, endometrioid type endometrial cancer (EC). The introduction of a molecular diagnostic framework by the TCGA Research Network in 2013, categorizing tumors into four prognostic groups, has significantly influenced the prognosis prediction in EC. The ProMisE system further stratifies EC based on molecular profiles, highlighting the need for refined prognostic tools, especially for those undergoing conservative treatments. Our study aims to explore the effectiveness of ProMisE and various immunohistochemical (IHC) markers in predicting outcomes for more fertility-sparing progestin therapy in endometrial cancer. Methods: We included young EC patients treated with fertility-sparing progestin therapy at a single center between January 2011 and December 2020. Patients were categorized according to the results of IHC staining to detect mismatch repair (MMR) proteins and p53 and the results of DNA polymerase epsilon (POLE) mutations which were identified through hotspot sequencing with droplet digital polymerase chain reaction like ProMisE classification. We also measured L1CAM, β-catenin, ER, and PR expression levels through IHC staining. The Complete Response (CR) rate to progestin therapy and PFS after progestin therapy were analyzed between each biomarker-driven subgroup. Results: Out of 104 patients, 60 patients (57.7%) were treated with MPA alone, while 44 patients (42.3%) received a combination of MPA and LNG-IUS. The CR was observed in 64 patients (61.5%). Among those achieving CR, 31 patients (48.4%) experienced recurrence over a median follow-up period of 54.7 months (range:10-128 months). The 5-year PFS was recorded at 67.2%, and the 5-year OS was maintained at 100%. Each one patient showed a POLE mutation, MMRd, and P53 abnormality, leaving 101 (97.1%) with NSMP. IHC revealed L1CAM expression in 12 patients (11.5%) and dual membranous and nuclear β-catenin expression in 8 patients (7.7%). This β-catenin expression significantly correlated with higher CR rates (71.4% vs. 45.6%, p=0.022), while L1CAM presence significantly reduced PFS (3yr-PFS 28.6% vs. 53.9%, p=0.033). Conclusions: Almost all endometrium-confined, low-grade, endometrioid type EC were categorized to NSMP, so that molecular classification had little role in young women who received fertility-sparing progestin therapy. Rather, β-catenin emerges as a positive predictive biomarker for CR, and L1CAM as a negative prognostic biomarker for PFS in this treatment setting. This supports incorporating these IHC markers into molecular classifiers like ProMisE for enhanced risk stratification and personalized treatment in this disease setting.
Additional copies of 1q negatively impact the outcome of multiple myeloma patients and induce transcriptomic deregulation in malignant plasma cells
Authors: Mattia D’Agostino, Delia Rota-Scalabrini, Angelo Belotti, Luca Bertamini, Maddalena Arigoni, Giovanni De Sabbata, Giuseppe Pietrantuono, Anna Pascarella, Patrizia Tosi, Francesco Pisani, Norbert Pescosta, Marina Ruggeri, Jennifer Rogers, Martina Olivero, Mariagrazia Garzia, Piero Galieni, Ombretta Annibali, Federico Monaco, Anna Marina Liberati, Salvatore Palmieri, Paola Stefanoni, Elena Zamagni, Benedetto Bruno, Raffaele Adolfo Calogero, Mario Boccadoro, Pellegrino Musto, Francesca Gay
Journal: Blood Cancer Journal (2024)

Additional copies of chromosome 1 long arm (1q) are frequently found in multiple myeloma (MM) and predict high-risk disease. Available data suggest a different outcome and biology of patients with amplification (Amp1q, ≥4 copies of 1q) vs. gain (Gain1q, 3 copies of 1q) of 1q. We evaluated the impact of Amp1q/Gain1q on the outcome of newly diagnosed MM patients enrolled in the FORTE trial (NCT02203643). Among 400 patients with available 1q data, 52 (13%) had Amp1q and 129 (32%) Gain1q. After a median follow-up of 62 months, median progression-free survival (PFS) was 21.2 months in the Amp1q group, 54.9 months in Gain1q, and not reached (NR) in Normal 1q. PFS was significantly hampered by the presence of Amp1q (HR 3.34 vs. Normal 1q, P < 0.0001; HR 1.99 vs. Gain1q, P = 0.0008). Patients with Gain1q had also a significantly shorter PFS compared with Normal 1q (HR 1.68, P = 0.0031). Concomitant poor prognostic factors or the failure to achieve MRD negativity predicted a median PFS < 12 months in Amp1q patients. Carfilzomib-lenalidomide-dexamethasone plus autologous stem cell transplantation treatment improved the adverse effect of Gain1q but not Amp1q. Transcriptomic data showed that additional 1q copies were associated with deregulation in apoptosis signaling, p38 MAPK signaling, and Myc-related genes.
Participation of patients with gynecological cancer in phase 1 clinical trials: Experience from 2 NCI-Designated Comprehensive Cancer Centers.
Authors: Anusha Adkoli, Krystle Vera, Patrick Glennan, Kevin Yeung, Demmie Aguilar, Mohammad Ghalib, Imran Chaudhary, Radhashree Maitra, Eugenia Girda, Sanjay Goel
Journal: Journal of Clinical Oncology (2024)

e17610 Background: Phase 1 trials are intended to define the safety of novel therapeutics, yet they offer alternate options long before they are approved. There is limited data regarding access and participation in phase 1 trials for gynecologic oncology patients. The purpose of this study is to assess the efficacy of phase 1 trials and to study factors of demographics, tumor characteristics, and toxicities impacting this population group. Methods: This IRB approved study was conducted via retrospective chart review at the Rutgers Cancer Institute of New Jersey and the Montefiore Einstein Comprehensive Cancer Center. Relevant variables were collected for all gynecologic oncology patients enrolled in phase 1 trials between 2000-2022. Data analysis was completed in a primarily descriptive manner. Results: Of the 335 patients enrolled, 72.2% were &lt; 65 years of age; diagnoses of the 335 patients included ovarian/fallopian tube/peritoneal/mullerian (58.0%), uterine (26.3%), cervical (15.2%), vaginal (0.3%), and vulvar (0.3%) cancers. Patients were 50.5% White, 24.2% Black, 18.2% Hispanic, and 6.6% Asian. Trend over-time analysis (enrollment between 2000-2011 compared to 2012-2022) showed that enrollment of White patients stayed stable (51.0/50.4%), Hispanic (16.0/21.6%) and Asian (3.1%/11.5%) increased, while enrollment decreased for Black patients (29.9/16.5%). Most patients had an ECOG performance status of 1 (74.0%). Prior number of regimens received by patients included 1-3 (52.0%), 4-7 (38.1%), and 8 or more (9.4%). The median number of prior lines was 3. Metastatic disease sites included lymph nodes (51.3%), abdominal/pelvic cavity (39.4%), lung (35.8%) and liver (34.0%). Highest grade hematologic toxicities were 3 or 4 in 18.2% of patients. For non-hematologic toxicities, 28% of patients experienced grade 3-5 events. Among non-hematologic adverse events, the most common grade 3-5 events were fatigue (1.2%), diarrhea (1.1%), vomiting (0.9%), and pain (0.9%). Only 3.9% had a dose limiting toxicity. Efficacy included complete response in 1.2%, partial response in 7.0%, stable disease in 40.2%, progressive disease in 37.8%, and not evaluable in 13.4%. Median OS was 37.9 weeks. There was no difference in OS between the races (p=0.11). Conclusions: Patients with gynecologic cancers often enrolled into phase 1 trials later in the course of their disease. Most patients had stable disease and although low grade toxicities were common, very few patients experienced a DLT, suggesting that phase 1 trials are tolerable and can be considered earlier in a patient’s clinical course. This illustrates the ongoing necessity to implement strategies to overcome disparities among patients participating in early phase clinical trials, especially given the similar OS experience.
Effectiveness of gel-immersion endoscopy for examination for suspected pancreaticobiliary maljunction
Authors: Koichi Soga, Takeshi Fujiwara, Fuki Hayakawa, Ikuhiro Kobori, Masaya Tamano
Journal: Endoscopy (2024)

Pancreaticobiliary maljunction (PBM) is a congenital anomaly in which the pancreatic and bile ducts join outside the duodenal wall and pancreatic juices and bile flow into a single channel [1]. Endoscopic retrograde cholangiopancreatography (ERCP) clearly shows the connecting structures and is the most effective method for detecting PBM (sensitivity, 90%–100%) [2]. Here, we aim to show the effectiveness of gel-immersion endoscopy for diagnostic differentiation and/or examination of PBM.
Splenic artery aneurysm masquerading as an intraductal tubulopapillary neoplasm diagnosed by contrast-enhanced endoscopic ultrasound
Authors: Takeshi Ogura, Kimi Bessho, Nobuhiro Hattori, Jun Matsuno, Hiroki Nishikawa
Journal: Endoscopy (2024)

The growth of intraductal tubulopapillary neoplasms is characterized by features such as filling, expansion, and proliferation of the main pancreatic duct (MPD) [1]. The resultant obstruction to the flow of pancreatic juice leads to MPD dilatation but, unlike with intraductal papillary mucinous neoplasms, cystic lesions and mucus are not observed. Splenic artery aneurysm, which is a rare condition, mainly occurs in the distal third of the splenic artery [2]. Although splenic artery aneurysms are usually asymptomatic [3], rupture of the aneurysm can cause dramatic hypotensive shock, with a high mortality rate owing to intraperitoneal hemorrhage. Rarely, hemosuccus pancreaticus can occur because of rupture of a splenic artery aneurysm into the MPD [4]. In this condition, differentiating between an intraductal tubulopapillary neoplasm and a splenic artery aneurysm is not very challenging because splenic artery aneurysmal rupture is normally symptomatic; however, if a splenic artery aneurysm spontaneously ruptures into the MPD and immediately stops bleeding, the differential diagnosis can be challenging. We herein describe successful differentiation between these diseases using contrast-enhanced endoscopic ultrasound (EUS).
DCRM 2.0: Multispecialty practice recommendations for the management of diabetes, cardiorenal, and metabolic diseases
Authors: Yehuda Handelsman, John E. Anderson, George L. Bakris, Christie M. Ballantyne, Deepak L. Bhatt, Zachary T. Bloomgarden, Biykem Bozkurt, Matthew J. Budoff, Javed Butler, David Z.I. Cherney, Ralph A. DeFronzo, Stefano Del Prato, Robert H. Eckel, Gerasimos Filippatos, Gregg C. Fonarow, Vivian A. Fonseca, W. Timothy Garvey, Francesco Giorgino, Peter J. Grant, Jennifer B. Green, Stephen J. Greene, Per-Henrik Groop, George Grunberger, Ania M. Jastreboff, Paul S. Jellinger, Kamlesh Khunti, Samuel Klein, Mikhail N. Kosiborod, Pamela Kushner, Lawrence A. Leiter, Norman E. Lepor, Christos S. Mantzoros, Chantal Mathieu, Christian W. Mende, Erin D. Michos, Javier Morales, Jorge Plutzky, Richard E. Pratley, Kausik K. Ray, Peter Rossing, Naveed Sattar, Peter E.H. Schwarz, Eberhard Standl, P. Gabriel Steg, Lale Tokgözoğlu, Jaakko Tuomilehto, Guillermo E. Umpierrez, Paul Valensi, Matthew R. Weir, John Wilding, Eugene E. Wright
Journal: Metabolism (2024)
Novel grasp-and-snare technique for efficient endoscopic necrosectomy of walled-off necrosis
Authors: Haruka Toyonaga, Tsuyoshi Hayashi, Kazuki Hama, Toshifumi Kin, Masayo Motoya, Kuniyuki Takahashi, Akio Katanuma
Journal: Endoscopy (2024)

Walled-off necrosis (WON) is a significant local complication of severe pancreatitis. Despite the utilization of endoscopic ultrasound-guided drainage, if necrotic debris accumulates within the WON and infection remains uncontrolled, direct endoscopic necrosectomy (DEN) is performed using auxiliary instruments such as forceps or snares [1] [2]. Conventional techniques often involve prolonged and multiple sessions because of their limited ability to remove necrotic material, leading to a substantial patient burden. Here we present an efficient adaptation of the two-channel method [3], commonly utilized for endoscopic mucosal resection ([Fig. 1]), for DEN, termed the "grasp-and-snare" technique. The procedure involves the use of a dual-channel endoscope (GIF-2TQ260M; Olympus, Tokyo, Japan), with one channel used to insert forceps for grasping and pulling lesions toward the operator and the other channel used to insert a snare for resecting the lesions. This technique enables simultaneous traction and snaring, rendering DEN safe and efficient ([Fig. 2], [Video 1]).
An Active Self‐Mitochondria‐Targeting Cyanine Immunomodulator for Near‐Infrared II Fluorescence Imaging‐Guided Synergistic Photodynamic Immunotherapy
Authors: Jin‐Feng Yu, Yu Wen, Ming Li
Journal: Advanced Healthcare Materials (2024)

Abstract Photodynamic therapy targeting mitochondria represents a promising therapeutic strategy for fighting diverse types of cancers. However, the currently available photosensitizers (PSs) suffer from insufficient therapeutic potency, limited mitochondria delivery efficiency, and the inability to treat invisible metastatic distal cancers. Herein, an active self‐mitochondria‐targeting heptapeptide cyanine (HCy) immunomodulator (I 2 HCy‐QAP) is reported for near‐infrared II (NIR‐II) fluorescence imaging‐guided photodynamic immunotherapy of primary and distal metastatic cancers. The I 2 HCy‐QAP is designed by introducing a quaternary ammonium salt with a phenethylamine skeleton (QAP) into the iodinated HCy photosensitizer. The I 2 HCy‐QAP can precisely target mitochondria due to the lipophilic cationic QAP unit, present strong NIR‐II fluorescence tail emission, and effectively generate singlet oxygen 1 O 2 under NIR laser irradiation, thereby inducing mitochondria‐targeted damages and eliciting strong systemic immunogenic cell death immune responses. The combination of the I 2 HCy‐QAP‐mediated photodynamic immunotherapy with anti‐programmed death‐1 antibody therapy achieves remarkable therapeutic efficacy against both primary and distal metastatic cancers with significant inhibition of lung metastasis in a triple‐negative breast cancer model. This work provides a new concept for designing high‐performance NIR emissive cyanine immunomodulators for NIR‐II fluorescence‐guided photodynamic immunotherapy.
The sword in the wall: managing biliary stents embedded in the duodenal wall following ERCP for biliary strictures after liver transplantation in an adult and a pediatric patient
Authors: Giacomo Emanuele Maria Rizzo, Ilaria Tarantino, Lucio Carrozza, Dario Ligresti, Gabriele Rancatore, Marco Giacchetto, Mario Traina
Journal: Endoscopy (2024)

We present the minimally invasive management of a rare delayed complication that can occur after biliary stenting for benign biliary anastomotic stricture (BBAS) after orthotopic liver transplantation (OLT).
Flaring Inflammation and ER Stress by an Organelle‐Specific Fluorescent Cage
Authors: Aliyah Fakim, Batoul I. Maatouk, Bappa Maiti, Avishek Dey, Shahad H. Alotaiby, Basem A. Moosa, Weibin Lin, Niveen M. Khashab
Journal: Advanced Healthcare Materials (2024)

Abstract The endoplasmic reticulum (ER) plays an important role in protein synthesis and its disruption can cause protein unfolding and misfolding. Accumulation of such proteins leads to ER stress, which ultimately promotes many diseases. Routine screening of ER activity in immune cells can flag serious conditions at early stages, but the current clinically used bio‐probes have limitations. Herein, an ER‐specific fluorophore based on a biocompatible benzothiadiazole‐imine cage (BTD‐cage) with excellent photophysical properties is developed. The cage outperforms commercially available ER stains in long‐term live cell imaging with no fading or photobleaching over time. The cage is responsive to different levels of ER stress where its fluorescence increases accordingly. Incorporating the bio‐probe into an immune disorder model, a 6‐, 21‐, and 48‐fold increase in intensity is shown in THP‐1, Raw 246.7, and Jurkat cells, respectively (within 15 min). These results strongly support that this system can be used for rapid visual and selective detection of ER stress. It is envisaged that tailoring molecular interactions and molecular recognition using supramolecular improved fluorophores can expand the library of biological probes for enhanced selectivity and targetability toward cellular organelles.
When I use a word . . . The languages of medicines—US proprietary names
Authors: Jeffrey K Aronson
Journal: BMJ (2024)

In the world of medicines, proprietary names are the brand names or trade names that pharmaceutical manufacturers give to their medicinal products. They are distinct from the generic names of the active ingredients they contain. Here I discuss the 2020 guidelines, published by the US Food and Drug Administration (FDA), on the desiderata governing a manufacturer's choice of a proprietary name for a medicinal product, having previously discussed the 2019 regulatory guidelines issued by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. The recommendations listed in the FDA's document are just that, recommendations not requirements, even though they are backed by the provisions of the 1938 US Federal Food, Drug, and Cosmetic Act (FD&amp;C Act) and its implementing regulations.
Cystogastrostomy as an alternative treatment for recurrent huge infected hepatic cyst
Authors: Hau-Jyun Su, Ting-An Lin, Ssu-Yu Chen, Ming-Chang Tsai, Edy Kornelius, Yu-Ting Lin, Chi-Chih Wang
Journal: Endoscopy (2024)

A 73-year-old woman with a history of polycystic liver and kidney disease (PLKD) presented with coffee grounds emesis, hypotension, and acute on chronic renal failure. She developed septic shock and a decline in renal function, necessitating emergency hemodialysis after admission. She had undergone robotic fenestration of a large hepatic cyst 5 months earlier because of acute cholangitis resulting from compression of the common bile duct by the cyst. Esophagogastroduodenoscopy revealed duodenal ulcer and lumen narrowing at the second portion of the duodenum ([Fig. 1] a). Magnetic resonance cholangiopancreatography confirmed a recurrent huge hepatic cyst at segment IV of the liver with air-fluid level ([Fig. 1] b).
Long-term colchicine for the prevention of vascular recurrent events in non-cardioembolic stroke (CONVINCE): a randomised controlled trial
Authors: Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly, Peter Kelly
Journal: The Lancet (2024)
FEASIBILITY AND SAFETY OF A DEDICATED CAUTERY-ENHANCED TUBULAR SELF-EXPANDABLE METAL STENT FOR ENDOSCOPIC ULTRASOUND-GUIDED HEPATICOGASTROSTOMY
Authors: Jorge Vargas-Madrigal, Shannon M. Chan, Jahnvi Dhar, Anthony Y.B. Teoh, Jayanta Samanta, Sundeep Lakhtakia, Marc Giovannini
Journal: Endoscopy (2024)

Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is an alternative for biliary drainage in patients with obstructive pancreaticobiliary pathology when endoscopic retrograde cholangiopancreatography (ERCP) is not feasible. Despite its effectiveness, EUS-HGS is associated with a significant risk of adverse events. This study aimed to evaluate the feasibility and safety of a newly designed dedicated cautery-enhanced tubular self-expandable metal stent (SEMS) for EUS-HGS.
Peroral cholangioscopy-guided diagnosis and treatment of Clonorchis sinensis liver flukes
Authors: Li-ying Tao, Hong-guang Wang, Qing-mei Guo, Shi-zhu Liu, Xiang Guo, Mu-yu Yang, Geng-jun Shi
Journal: Endoscopy (2024)

An 80-year-old man presented to our hospital with pain in the right upper quadrant of the abdomen that started 2 weeks prior to presentation. Laboratory analysis showed elevated C-reactive protein without leukocytosis. A transabdominal ultrasound showed dilated intrahepatic and extrahepatic bile ducts and gallbladder deposits. After obtaining informed consent, endoscopic ultrasonography (EUS) was pursued to explore the etiology for this biliary abnormality.
Eating Around the Clock: Circadian Rhythms of Eating and Metabolism
Authors: Andrew W. McHill, Matthew P. Butler
Journal: Annual Review of Nutrition (2024)

The time of day that we eat is increasingly recognized as contributing as importantly to overall health as the amount or quality of the food we eat. The endogenous circadian clock has evolved to promote intake at optimal times when an organism is intended to be awake and active, but electric lights and abundant food allow eating around the clock with deleterious health outcomes. In this review, we highlight literature pertaining to the effects of food timing on health, beginning with animal models and then translation into human experiments. We emphasize the pitfalls and opportunities that technological advances bring in bettering understanding of eating behaviors and their association with health and disease. There is great promise for restricting the timing of food intake both in clinical interventions and in public health campaigns for improving health via nonpharmacological therapies.
Comparison of incidence, causes and prognosis of adult and paediatric epidermal necrolysis: a French population-based study
Authors: Thomas Bettuzzi, Anne Welfringer-Morin, Saskia Ingen-Housz-Oro, Pauline Bataille, Bénédicte Lebrun-Vignes, Christine Bodemer, Emilie Sbidian
Journal: British Journal of Dermatology (2024)

Epidermal necrolysis (EN), comprising Stevens-Johnson syndrome and toxic EN, is a rare and severe blistering reaction, mainly induced by drugs. Differences between paediatric and adult patients regarding incidence, causes and outcomes have been discussed but are based on a limited number of patients from small case series. To directly compare the incidence, cause and prognosis of adult and paediatric EN. We used data from the French Health System Database (1 January 2013-31 December 2022). We identified adult and paediatric patients hospitalized for EN using the International Classification of Diseases, 10th Revision codes combined with validated algorithms. Outcomes were the incidence of EN; the presence of a suspected drug before EN onset (defined as a new drug dispensation from 5 to 56 days prehospitalization); and in-hospital mortality. To estimate the association between paediatric EN and the presence of a suspect drug, we computed a multivariable logistic regression with odd ratios (ORs). To estimate the association with mortality, we computed a multivariable Cox proportional hazard ratio (HR) model. A total of 1440 patients [799 (55.5%) female] with EN were included, comprising 219 children and 1221 adults. Among children, the incidence of EN was 1.5 cases [95% confidence interval (CI) 1.3-1.7] per 1 million person-years vs. 2.6 cases (95% CI 2.5-2.7) in adults. Moreover, children had less chance of being given a culprit drug before the onset of EN [n = 93/219 (42.5%) vs. n = 829/1221 (67.9%)], with an adjusted OR of 0.43 (95% CI 0.32-0.59; P < 0.001), together with a better prognosis: the mortality rate in paediatric patients was 1.4% (95% CI 0.4-3.7) vs. 19.4% (95% CI 17.3-21.7) in adults. The adjusted HR for in-hospital mortality in children was 0.12 (95% CI 0.04-0.38; P < 0.001). Paediatric EN appears to be rarer, with less chance of being caused by drugs and has a better prognosis than adult EN. These results suggest the existence of different underlying pathophysiological mechanisms and clinical particularities between adult and paediatric patients with EN.