tbuckley/cabot-search huggingface dataset:
Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): Primary results from DESTINY-Breast06 (DB-06).
Authors: Giuseppe Curigliano, Xichun Hu, Rebecca Alexandra Dent, Kan Yonemori, Carlos H. Barrios, Joyce O'Shaughnessy, Hans Wildiers, Qingyuan Zhang, Seock-Ah Im, Cristina Saura, Laura Biganzoli, Joohyuk Sohn, Christelle Levy, William Jacot, Natasha Begbie, Jun Ke, Gargi Surendra Patel, Aditya Bardia
Journal: Journal of Clinical Oncology (2024)

LBA1000 Background: T-DXd is approved for HER2-low (IHC 1+ or 2+/ISH-negative) mBC after ≥1 line of chemotherapy (CT). DB-06 (NCT04494425) evaluated T-DXd in pts with HER2-low or -ultralow (IHC 0 with membrane staining), HR+ mBC after disease progression (PD) on endocrine-based therapy and no prior CT for mBC. Methods: Pts with HER2-low or -ultralow, HR+ mBC were randomized 1:1 to T-DXd 5.4 mg/kg or TPC. Pts had no prior CT for mBC, with ≥2 lines of ET for mBC, or 1 line of ET for mBC if PD occurred ≤24 months (mo) of adjuvant ET or ≤6 mo of ET+CDK4/6i for mBC. Primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR) in HER2-low. Key secondary endpoints were PFS in intent-to-treat (ITT = HER2-low and -ultralow) and overall survival (OS). Other endpoints included objective response rate (ORR) and safety. Results: As of Mar 18, 2024, 866 pts (HER2-low, n=713; HER2-ultralow, n=153) were randomized; 90.4% had prior CDK4/6i. TPC group pts were selected for capecitabine (59.8%), nab-paclitaxel (24.4%) or paclitaxel (15.8%). T-DXd significantly improved PFS vs TPC in HER2-low (HR, 0.62 [95% CI 0.51, 0.74], P&lt;0.0001; median, 13.2 vs 8.1 mo). ITT and HER2-ultralow results were consistent with HER2-low (Table). Median treatment duration was 11.0 mo (T-DXd) vs 5.6 mo (TPC). OS was immature at first interim analysis (HER2-low HR, 0.83 [95% CI 0.66, 1.05], P=0.1181; median follow up, 18.6 mo). Grade (Gr) ≥3 drug-related adverse events occurred in 40.6% (T-DXd) vs 31.4% (TPC). Adjudicated interstitial lung disease / pneumonitis occurred in 49 (11.3%; 0.7% Gr 3/4, 0.7% Gr 5) vs 1 (0.2% Gr 2) pts receiving T-DXd vs TPC. Conclusions: T-DXd showed a statistically significant and clinically meaningful PFS benefit vs TPC (CT) in HER2-low mBC. HER2-ultralow results were consistent with HER2-low. Safety was in line with known profiles. DB-06 establishes T-DXd as a standard of care following ≥1 endocrine-based therapy for pts with HER2-low and -ultralow, HR+ mBC. Clinical trial information: NCT04494425 .[Table: see text]
Biodegradable high-nitrogen iron alloy anastomotic staples: In vitro and in vivo studies
Authors: Sihan Lu, Peng Wang, Qingchuan Wang, Peng Deng, Yonghui Yuan, Xiaoqing Fu, Yinghui Yang, Lili Tan, Ke Yang, Xun Qi
Journal: Bioactive Materials (2024)

For gastrointestinal anastomosis, metallic biodegradable staples have a broad application potential. However, both magnesium and zinc alloys have relatively low strength to withstand the repeated peristalsis of the gastrointestinal tract. In this study, we developed a novel kind of biodegradable high-nitrogen iron (HN–Fe) alloy wires (0.23 mm), which were fabricated into the staples. The tensile results showed that the ultimate tensile strength and elongation of HN–Fe wires were 1023.2 MPa and 51.0 %, respectively, which was much higher than those of other biodegradable wires. The degradation rate in vitro of HN–Fe wires was slightly higher than that of pure Fe wires. After 28 days of immersion, the tensile strength of HN–Fe wires remained not less than 240 MPa, meeting the clinical requirements. Furthermore, sixteen rabbits were enrolled to conduct a comparison experiment using HN–Fe and clinical Ti staples for gastroanastomosis. After 6 months of implantation, a homogeneous degradation product layer on HN–Fe staples was observed and no fracture occurred. The degradation rate of HN–Fe staples in vivo was significantly higher than that in vitro, and they were expected to be completely degraded in 2 years. Meanwhile, both benign cutting and closure performance of HN–Fe staples ensured that all the animals did not experience hemorrhage and anastomotic fistula during the observation. The anastomosis site healed without histopathological change, inflammatory reaction and abnormal blood routine and biochemistry, demonstrating good biocompatibility of HN–Fe staples. Thereby, the favorable performance makes the HN–Fe staples developed in this work a promising candidate for gastrointestinal anastomosis.
Preventive effect of naldemedine for opioid-induced constipation in patients with cancer starting opioids: A multicenter, double-blinded, randomized, placebo-controlled, phase 3 trial.
Authors: Jun Hamano, Takahiro Higashibata, Takaomi Kessoku, Shinya Kajiura, Mami Hirakawa, Keisuke Ariyoshi, Shunsuke Oyamada
Journal: Journal of Clinical Oncology (2024)

LBA12014 Background: A peripherally acting μ-opioid receptor antagonist (PAMORA), such as naldemedine, could alleviate OIC in cancer patients. However, the evidence of PAMORA on OIC prevention in cancer patients starting opioid analgesia is limited. This clinical trial aimed to confirm the preventive effect of naldemedine for OIC in cancer patients who start daily strong opioid administration compared with placebo. Methods: We conducted a multicenter, double-blinded, randomized, placebo-controlled trial between July 2021 and May 2023 with four academic hospital in Japan (jRCTs031200397). Patients with cancer starting regular strong opioid for the first time for cancer pain, and age 20 years or older were included. The eligible patient was randomly assigned to the naldemedine (Symproic 0.2 mg) or placebo group in a 1:1 ratio. The protocol treatment period was 14 days after the start of naldemedine (or placebo) and the naldemedine group had Symproic at 0.2 mg once a day after breakfast for 14 days. The placebo group had the placebo once a day after breakfast for 14 days. The primary endpoint was the proportion of patients with a Bowel Function Index (BFI) of less than 28.8 on Day 14. We conducted the safety assessments with the number of all adverse events occurring during the protocol treatment period using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Japanese translation of Japan Clinical Oncology Group. Results: Of the 103 patients were assessed for eligibility, 99 patients were randomly assigned on a 1:1 basis to receive naldemedine (n = 49) or placebo (n = 50). The BFI score at Day 1 was 18.3±19.8 with naldemedine group and 18.2±20.0 with placebo. The proportion of patients with a BFI of less than 28.8 on Day 14 was significantly greater with naldemedine group (64.6% [31 of 48 patients]; 95% CI, 51.1% to 78.1%) than with placebo (17.0% [8 of 47 patients]; 95% CI, 6.3% to 27.8%) with a difference of 47.6% (95% CI, 30.3% to 64.8%, p&lt; 0.0001). There was no statistical difference in the proportion of adverse events; abdominal distention, abdominal pain, diarrhea, bowel obstruction, and nausea. However, there was a significantly lower proportion of vomiting in patients treated with naldemedine. During the treatment period, none of patients treated with naldemedine had diarrhea, nausea, or vomiting as adverse events causally related to protocol treatment (0.0% [0 of 48 patients] v.s 34.0% [16 of 47 patients]. Conclusions: Naldemedine is a valuable option with proven efficacy in preventing OIC in cancer patients starting regular strong opioids. Clinical trial information: 031200397 .
A set of circulating microRNAs belonging to the 14q32 chromosome locus identifies two subgroups of individuals with recent-onset type 1 diabetes
Authors: Guido Sebastiani, Giuseppina Emanuela Grieco, Marco Bruttini, Stefano Auddino, Alessia Mori, Mattia Toniolli, Daniela Fignani, Giada Licata, Elena Aiello, Laura Nigi, Caterina Formichi, Juan Fernandez-Tajes, Alberto Pugliese, Carmella Evans-Molina, Lut Overbergh, Timothy Tree, Mark Peakman, Chantal Mathieu, Francesco Dotta
Journal: Cell Reports Medicine (2024)

Circulating microRNAs (miRNAs) are linked to the onset and progression of type 1 diabetes mellitus (T1DM), thus representing potential disease biomarkers. In this study, we employed a multiplatform sequencing approach to analyze circulating miRNAs in an extended cohort of prospectively evaluated recent-onset T1DM individuals from the INNODIA consortium. Our findings reveal that a set of miRNAs located within T1DM susceptibility chromosomal locus 14q32 distinguishes two subgroups of individuals. To validate our results, we conducted additional analyses on a second cohort of T1DM individuals, confirming the identification of these subgroups, which we have named cluster A and cluster B. Remarkably, cluster B T1DM individuals, who exhibit increased expression of a set of 14q32 miRNAs, show better glycemic control and display a different blood immunomics profile. Our findings suggest that this set of circulating miRNAs can identify two different T1DM subgroups with distinct blood immunomics at baseline and clinical outcomes during follow-up.
PRGN-2012, a novel gorilla adenovirus-based immunotherapy, provides the first treatment that leads to complete and durable responses in recurrent respiratory papillomatosis patients.
Authors: Scott Norberg, James L. Gulley, Jeffrey Schlom, Amy Lankford, Roshanak Semnani, Rutul R. Shah, Douglas E Brough, Helen Sabzevari, Clint Allen
Journal: Journal of Clinical Oncology (2024)

LBA6015 Background: Recurrent respiratory papillomatosis (RRP) is a rare, neoplastic disorder caused by chronic infection with human papillomavirus (HPV) type 6 or 11. Significant morbidity can occur due to airway obstruction and, although rare, transformation into malignant cancer. There are no approved therapeutics. RRP is currently managed with frequent ablative procedures that can lead to irreversible laryngotracheal scarring and disability. PRGN-2012 is a gorilla adenovirus-based gene therapy/immunotherapy designed to generate HPV6/11-specific T cell immunity. The FDA has granted PRGN-2012 Breakthrough Therapy Designation for the treatment of RRP recognizing that this single arm study can serve as pivotal to support a licensing application. Methods: This pivotal trial (NCT04724980) evaluates the safety and efficacy of PRGN-2012 in patients with RRP requiring a minimum of 3 surgeries in the 12 months prior to treatment. Eligible patients received 4 subcutaneous (SC) injections of PRGN-2012 at dose level (DL) 1 (1x10 11 Particle Units (PU) per injection; n=3) or DL2 (5x10 11 PU per injection; n=35) over 12 weeks. The primary endpoint was the rate of complete response (CR), defined as no requirement for surgery in the 12 months following completion of treatment. Other key endpoints include duration of response, change in extent of papilloma growth (anatomic Derkay score) and vocal function. Results: PRGN-2012 was well-tolerated, with no serious adverse events, grade &gt; 2 treatment-related adverse events, or early treatment discontinuations. The most common adverse events were injection-site reaction, fatigue, chills, fever, and myalgia. PRGN-2012 treatment at DL2 significantly (p&lt;0.0001) decreased the requirement for surgery, with a median number of surgeries in the 12 month period decreasing from 4 (3-10) prior to treatment to 0 (0-7) surgeries post-treatment. Approximately 90% of patients experienced a decrease in the number of surgeries in the 12 months post-treatment compared to pre-treatment with PRGN-2012. The primary endpoint evaluation demonstrated a confirmed complete response in 17/31 (55%) of evaluable patients. The median duration of complete response has yet to be reached with a median follow up of 15 months (12 - 30) at the time of data cutoff (March 6, 2024). Additionally, PRGN-2012 treatment resulted in a significant reduction in Derkay score, improvement in vocal function and generation of HPV-specific immune responses. Conclusions: These data demonstrate the overall favorable safety profile and significant clinical benefit of PRGN-2012 in adult RRP patients. These findings support PRGN-2012 as a potential therapeutic option for this patient population where no FDA-approved therapeutics exist. Clinical trial information: NCT04724980 .
First report of the use of a digital single-operator cholangioscope for endoscopic direct diverticulitis therapy
Authors: Jun Cai, Silin Huang, Yangbor Lu, Suhuan Liao, Guang Yang, Bo Li, Jianzhen Ren
Journal: Endoscopy (2024)

A 31-year-old man with a 2-day history of periumbilical abdominal pain was evaluated at our hospital. Abdominal computed tomography (CT) revealed ileocecal inflammation and multiple cecal diverticula ([Fig. 1] a). Colonoscopy identified several diverticula in the cecum, particularly one manifesting inflamed and edematous mucosa coated in yellowish-white purulent exudate ([Fig. 1] b). A continuous purulent discharge was noted.
EUS vs. ERCP-guided primary drainage of inoperable distal malignant biliary obstruction: systematic review and meta-analysis of randomized controlled trials
Authors: Tawfik Khoury, Wisam Sbeit, Andrea Lisotti, Bertrand Napoléon, Fabien Fumex, Giovanni Marasco, Leonardo H. Eusebi, Pietro Fusaroli, Shannon M. Chan, Amir Shahin, Maamoun Basheer, Rodica Gincul, Sarah Leblanc, Anthony Y. B. Teoh, Jérémie Jacques
Journal: Endoscopy (2024)

We assessed efficacy and safety of endoscopic ultrasound-guided biliary drainage (EUS-BD) vs. endoscopic retrograde cholangiopancreatography (ERCP) as first-line intervention in malignant distal biliary obstruction (MDBO).
Moving beyond hotspots of HIV prevalence to geospatial hotspots of UNAIDS 95-95-95 targets in sub-Saharan Africa
Authors: Diego F Cuadros, Qian Huang, Godfrey Musuka, Tafadzwa Dzinamarira, Brian K Moyo, Amon Mpofu, Tatenda Makoni, F DeWolfe Miller, Anna Bershteyn
Journal: The Lancet HIV (2024)
A Biodegradable Fiber Calcium Ion Sensor by Covalently Bonding Ionophores on Bioinert Nanoparticles
Authors: Sihui Yu, Chengqiang Tang, Sijia Yu, Wenjun Li, Jiajia Wang, Ziwei Liu, Xinheng Yan, Liyuan Wang, Yiqing Yang, Jianyou Feng, Jiaqi Wu, Kailin Zhang, Hang Guan, Yue Liu, Songlin Zhang, Xuemei Sun, Huisheng Peng
Journal: Advanced Healthcare Materials (2024)

Abstract Implantable sensors, especially ion sensors, facilitate the progress of scientific research and personalized healthcare. However, the permanent retention of implants induces health risks after sensors fulfill their mission of chronic sensing. Biodegradation is highly anticipated; while; biodegradable chemical sensors are rare due to concerns about the leakage of harmful active molecules after degradation, such as ionophores. Here, a novel biodegradable fiber calcium ion sensor is introduced, wherein ionophores are covalently bonded with bioinert nanoparticles to replace the classical ion‐selective membrane. The fiber sensor demonstrates comparable sensing performance to classical ion sensors and good flexibility. It can monitor the fluctuations of Ca 2+ in a 4‐day lifespan in vivo and biodegrade in 4 weeks. Benefiting from the stable bonding between ionophores and nanoparticles, the biodegradable sensor exhibits a good biocompatibility after degradation. Moreover, this approach of bonding active molecules on bioinert nanoparticles can serve as an effective methodology for minimizing health concerns about biodegradable chemical sensors.
Depression Symptoms in Patients with Cystic Fibrosis Fluctuate at Baseline and Improve with Elexacaftor/Tezacaftor/Ivacaftor Therapy
Authors: Linus Piehler, Ralf Thalemann, Christine Lehmann, Mirjam Stahl, Marcus A. Mall, Simon Y. Graeber
Journal: American Journal of Respiratory and Critical Care Medicine (2024)
Non-Linear Association of P<sub>0.1</sub> and Patient Survival
Authors: Sakina Kadomatsu, Tomohiro Shinozaki, Mikio Nakajima, Tadahiro Goto
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Non-Linear Association of P0.1 and Patient Survival." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Baseline viral load in chronic hepatitis B may be clinically significant but must be interpreted with caution
Authors: Tong Tang, Li-Qin Li, Zhao-Di Wang
Journal: Hepatology (2024)

Department of Rehabilitation Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China Correspondence Zhao-Di Wang, Department of Rehabilitation Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China. Email: [email protected]
Neoadjuvant camrelizumab plus apatinib for locally advanced microsatellite instability-high or mismatch repair-deficient colorectal cancer (NEOCAP): a single-arm, open-label, phase 2 study
Authors: Jie-Hai Yu, Bin-Yi Xiao, Dan-Dan Li, Wu Jiang, Ya Ding, Xiao-Jun Wu, Rong-Xin Zhang, Jun-Zhong Lin, Wei Wang, Kai Han, Ling-Heng Kong, Xin-Ke Zhang, Bi-Yun Chen, Wei-Jian Mei, Zhi-Zhong Pan, Jing-Hua Tang, Xiao-Shi Zhang, Pei-Rong Ding
Journal: The Lancet Oncology (2024)
Gynecologic malignancies in women younger than 40 years of age: A SEER database review.
Authors: Princy Shah, Kashyap Kela, Upendra P. Hegde
Journal: Journal of Clinical Oncology (2024)

e17605 Background: Gynecologic malignancies are one of the most common types of cancers in women, but their Epidemiology in young women is not widely known. Here we present the demographics and comparison between uterine, cervical, ovarian, vagina, and vulvar cancers in women under age 40 years based on the Surveillance, Epidemiology, and End Results (SEER) database analysis. Methods: Information was collected from the SEER database November 2022 with the data from years 2000-2020 containing 17 registries. Site recode ICD O-3/WHO 2008 Female Genital system was applied and Primary sites labeled 51.8 to 56.9 were selected. Patient population with only one primary site of Malignancy was included, and the cases with No specific sites were excluded. Age recode 0-39 years was applied. Variables of Age group, Race, Ethnicity, Median household income, Areas of residence &amp; survival months were selected. Data was extracted for a total of 34056 patients. The Chi-square test was used for statistical analysis. P value &lt;0.05 was considered significant. Results: The most common site of Gynecologic cancer was Cervix (50.4%) followed by Uterus (24.2%) and Ovary (23%). Vulvar(1.9%) and Vaginal (0.6%) cancers were the rarest. Squamous cell carcinoma was the most common histology for cervical (42.9%), vaginal (26%), Vulvar (51%) cancer versus Endometrioid histology for uterine (69.2%) and teratoma for ovarian (12.5%) cancer. The most common age group affected was 34-39 (44.1%) with decreasing frequency with younger age. 30.5% of participants belonged to 30-34 years of age. A total of 14 cases were noted in patients less than 1 year of age with most cases of vaginal and ovarian cancer. Non-Hispanic whites had the highest occurrence (48.8%) followed by Hispanics (28.4%), Blacks (10.7 %), Asian/Pacific Islanders (9.7%), and Alaskan/American natives (1.2%). Compared to high household income, patients with lower household income of &lt;75,000 US dollars (USD) comprised of 61.9% of total Gynecologic malignancies. 89% of the total cases were observed in Metropolitan cities versus non-metropolitan areas. 5-year survival rate was observed at 57% overall. Vulvar cancer had the highest survival rate of 60.1% followed by Uterine (57.9%), Vaginal (57.1%), Cervix (56.1%), and Ovarian (56%) cancer. Conclusions: Early onset Gynecologic malignancies are more common in non-Hispanic whites, in Median Household income &lt;75,000 USD, and in Metropolitan cities. Incidence increases with age. Vulvar cancer has the best 5 years survival and Ovarian has the worst one. Cervical cancer (50.4% of total cases) screening should be continued as per current guidelines. However, with Uterine and Ovarian cancers collectively contributing to close to half the Gynecologic malignancies, Practitioners should maintain high clinical suspicion to have appropriate individualized workups based on Risk Factors for early Diagnosis and Management of these cancers in this age group.
Chemical hair relaxer use and its potential effect on incidence of endometrial cancer in Black women.
Authors: Tosha Hedin, Mahvish Haider
Journal: Journal of Clinical Oncology (2024)

e17591 Background: Research is being conducted to determine chemical hair relaxer’s effects on women’s risk of endometrial cancer (EC). Recent studies have suggested that frequent use (&gt;4 times/year) of chemical relaxers increases incidence of EC by a hazard ratio of 2.55. Black women purchase 60% of chemical straighteners in the United States while being 6.5% of the population. Hair relaxer can be made from sodium hydroxide, lithium hydroxide, or potassium hydroxide. These chemicals can cause a hormone imbalance with estrogen, leading to increased endometrial cancer incidence. This study aims to correlate population data of endometrial cancer and hair relaxer to explain the increased incidence of gynecologic cancer in Black women. Methods: The average rate of incidence per 100,00 per year for endometrial cancer for White and Black women were obtained from the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results Program SEER*Stat Database: NPCR and SEER Incidence – U.S. Cancer Statistics 2001–2019 Public Use Research Database. Chemical relaxer was first commercially available in 1971. The average age of endometrial cancer diagnosis was obtained from the National Cancer Institute. Results: Nineteen years of data was collected from the SEER database. EC had 222,464 cases total. In the year 2001, EC incidence was most common in White women at a rate of 25 per 100,000. Black women were second, at a rate of 20 per 100,000. In 2017, Black women surpassed White women for most incidence with a rate of 28, in comparison to White women's rate of 27.5 per 100,000. In the year 2019, Black women increased to the rate of 29 per 100,000, which was greater than White women's rate at 27.6 per 100,000. Conclusions: Studies have shown that ever use of hair relaxer in the past 12 months is associated with higher incidence of EC. The hazard ratio increases to 2.55 when hair relaxer is used 4 or more times per year. The National Cancer Institute states that the average age to be diagnosed with EC is 60 years old for all races of women. Because hair relaxer was made commercially available in 1971, the year 2017 would be when women at the average age of diagnosis would have access to hair relaxer their entire lives. 2017 is also the year when Black women became the racial group with the highest incidence of EC in the United States. Hair relaxer could be an important variable as to why EC incidence in Black women has surpassed White women. In the future, this information could be used to risk stratify women for cancer surveillance or have warning labels placed on hair relaxer boxes.