bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations of the hormones follitropin and lutropin in the blood of young mice dosed with lindane
Authors: Pérez-González Ernestina , Flores-Flores Frida Ariadna , Lugo-Martínez Perla Yareli , Herrera-Moreno María Nancy , Llanes-Cárdenas Omar , González-Ocampo Héctor Abelardo , Solis-Carrasco Jesús Daniel , Barraza-Tizoc Claudia Leonor , Enríquez-Verdugo Idalia , Almanza-Peñuelas Juan Francisco , Ramos-Beltrán Daniela Esmeralda , Salomón-Soto Víctor Manuel 
Published: May 2024

Abstract
Background
The gonadotropins lutropin and follitropin stimulate steroid synthesis in the gonads during gonadal maturation by promoting oogenesis and spermatogenesis. Endocrine disruptors such as lindane (γHCH) can alter the reproductive stage so and could alter puberty by interfering with lutropin and follitropin signaling. γHCH was classified by World Health Organization as “moderately restricted”, and in 2009 it is production and agricultural use was prohibited, under the Stockholm Convention, however, its use as a pharmaceutical treatment against lice and scabies is still allowed (and mainly, for use by the health sector). This study aimed to examine the effects of single-dose exposure to γHCH in young mice (Mus musculus) on lutropin and follitropin concentration, and to correlate gonadal maturity status and phenotypic characteristics.

Methods
Young γHCH-treated mice (16 females and 16 males) received a single dose of 25, 10, 5, or 0 µg/ml γHCH per gram of body weight, ocular route. Once secondary sexual characteristics were observed, the gonads were dissected and examined using histological techniques and the ovarian follicles were classified as dependent and independent of gonadotropins; the testicles were classified as inactive, early and late spermatogenesis; and the blood was processed with the lutropin and follitropin ELISA kit.

Results
The results indicate significant differences in the concentration of lutropin and follitropin between males and females (Fisher p < 0.05). The lutropin and follitropin levels showed a tendency to decrease in females, whereas, in males they tended to increase as the dose of γHCH increased. In females, it was observed that at the follitropin and lutropin decreased 42.3% and 83.7%, respectively at dose of 25 µg/ml; while in males, follitropin increased 51.9% at the dose of 25 µg/ml, and at the dose of 10 µg/ml lutropin increased by 242.5%. Contrary to that, gonadal maturity increased in females and decreased in males with increasing γHCH dose, disagreeing with the idea that gonadotropins coincide with the onset of puberty and gonadal maturity.

Conclusions
The results allow us to infer that exposure to γHCH could promote non-monotonic responses; however, this does not seem to alter puberty in the doses and conditions of the present experiment.
Bilateral simultaneous total knee arthroplasty with and without patellar resurfacing. A prospective single surgeon series with a minimum follow-up of 7 years
Authors: Alamino Leonel Perez , Garabano German , Pesciallo Cesar Ángel , Del Sel Hernán 
Published: May 2024

Abstract
Background
Total knee arthroplasty (TKA) is the most effective treatment for end-stage adult knee osteoarthritis, but it has been reported that patient satisfaction may vary. A malfunction of the patellofemoral joint may produce anterior knee pain (AKP) for several reasons. While some surgeons systematically resurface the patella despite the risk of potential complications such as fracture, loosening, or wear of the patella, others prefer to preserve it to reduce AKP and revision rates. This study aimed to evaluate whether patellar resurfacing had better clinical and functional outcomes, complications, and revision rates in patients undergoing simultaneous bilateral total knee arthroplasty.

Methods
We conducted a prospective cohort study, including patients who underwent bilateral simultaneous TKA in which the patella was replaced in one knee and preserved in the other, with a minimum follow-up of 7 years. We assessed clinical and functional outcomes with the Knee Society Score (KSS) and Visual Analogue Scale (VAS); complications and revision rates were also registered.

Results
The final series consisted of 43 patients with 86 knee arthroplasties. After a mean of 7.6 years of follow-up, no significant differences were found regarding KSS (clinical: 82.8 ± 7.4 versus 83.2 ± 3.4, p = 0.92; functional 89.1 ± 8.2: versus 90.4 ± 6.8; p = 0.99), VAS (2.0 ± 0.9 versus 1.8 ± 1.0; p = 0.84), complications (10.5% versus 8.1%; p = 0.57), or revision rates (2.3% versus 2.3%; p = 0.99) when comparing patellar resurfacing versus retention.

Conclusion
In the context of total knee arthroplasty, patellar replacement did not demonstrate statistically significant differences concerning patellar retention in clinical nor functional outcomes, AKP, complications, or revision rates after a minimum of 7 years of follow-up.
First-line inavolisib/placebo + palbociclib + fulvestrant (Inavo/Pbo+Palbo+Fulv) in patients (pts) with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced/metastatic breast cancer who relapsed during/within 12 months (mo) of adjuvant endocrine therapy completion: INAVO120 Phase III randomized trial additional analyses.
Authors: Juric Dejan , Kalinsky Kevin , Turner Nicholas C. , Jhaveri Komal L. , Schmid Peter , Loi Sherene , Saura Cristina , Im Seock-Ah , Sunpaweravong Patrapim , Li Huiping , Musolino Antonino , Zhang Qingyuan , Nowecki Zbigniew , Leung Roland Ching-Yu , Thanopoulou Eirini , Shankar Noopur , Lei Guiyuan , Devine Jacob , Stout Thomas J , Loibl Sibylle 
Published: May 2024

1003 Background: INAVO120 (NCT04191499) showed significantly and meaningfully improved investigator-assessed progression-free survival (PFS; stratified hazard ratio 0.43) with Inavo+Palbo+Fulv v Pbo+Palbo+Fulv, and manageable safety and tolerability. To further characterize the substantial benefit/risk of the Inavo triplet, we assessed additional clinically relevant efficacy endpoints, detailed safety data of key adverse events (AEs) for Inavo (hyperglycemia [HG], diarrhea, rash, stomatitis), and pt-reported outcomes (PROs). Methods: Efficacy endpoints includedtime from randomization to end of next-line treatment (tx; proxy for PFS2) and to first chemotherapy (TTFC). Key AEs were reported by grouped terms. PROs were assessed by PRO-CTCAE, an overall bother item, BPI-SF, and EORTC QLQ-C30. Results: Increases in median “PFS2” (24.0 v 15.1 mo; unstratified hazard ratio: 0.59 [95% CI, 0.42–0.83]) and TTFC (NE v 15.0 mo; unstratified hazard ratio: 0.53 [95% CI, 0.37–0.78]) were observed in the Inavo v Pbo arm (median follow-up: 21.3 mo; Table). Key AEs were mostly G1–2 and had resolved (Table). No key AEs were G4–5. In the Inavo arm, among pts who experienced key AEs (HG, diarrhea, rash, stomatitis), median time to first onset was 7, 15, 29, and 13 days, respectively. The key AEs were managed with standard supportive care and Inavo dose interruptions/reductions. One pt discontinued Inavo due to HG; one, due to stomatitis. Pts receiving Inavo experienced a longer duration of time without worsening pain severity and maintained their day-to-day functioning and health-related quality of life on tx. Most pts in both arms reported levels of selected symptomatic AEs from the PRO-CTCAE and overall tx bother as moderate or less, indicating that Inavo does not contribute additional tx burden. Conclusions: Inavo+Palbo+Fulv was associated with sustained benefit beyond disease progression, delaying chemotherapy administration, with manageable safety and tolerability that was reflected in PROs; hence, supporting it as a new standard of care. Clinical trial information: NCT04191499 . [Table: see text]
Enfortumab vedotin (EV) in triple-negative breast cancer (TNBC) and HR+/HER2- breast cancer (BC) cohorts of EV-202.
Authors: Giordano Antonio , Awan Arif Ali Ali , Yang Bruce Justine , Rugo Hope S. , Diamond Jennifer Robinson , Novik Yelena , Baranda Joaquina Celebre , Muro Kei , Ono Makiko , Nanda Rita , Kaplan Jason , Gorla Seema Rao , Liu Shubin , Wozniak Michele , Lee Anthony , Traina Tiffany A. 
Published: May 2024

1005 Background: EV, a Nectin-4–directed antibody–drug conjugate, is approved for use in urothelial cancer. Nectin-4 is expressed in several solid tumors, including BC. EV monotherapy was evaluated in TNBC and HR+/HER2- BC in EV-202 (NCT04225117). Methods: In this open-label, multicohort, phase 2 trial, eligible adults had locally advanced or metastatic (la/m) solid tumors, measurable disease, and ECOG PS 0–1. In BC cohorts, patients (pts) had prior taxanes or anthracyclines, ≥1 standard-of-care cytotoxic regimen and ≤2 lines (L) of cytotoxic therapy for la/mBC, and prior PD-1/L1 inhibitor (TNBC) or endocrine treatment (tx) with a CDK4/6 inhibitor (HR+/HER2- BC). Nectin-4 expression was not required but was assessed retrospectively. Pts received EV 1.25 mg/kg intravenously days 1, 8, and 15 of each 28-d cycle until discontinuation criteria (eg, disease progression, unacceptable toxicity) were met. Primary endpoint was confirmed objective response rate (ORR); ≥10 (TNBC) or ≥12 (HR+/HER2- BC) responders out of 40 evaluable pts were needed to claim promising antitumor activity. Secondary endpoints were duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety/tolerability. Antitumor activity was investigator-assessed per RECIST v1.1. Results: In the TNBC cohort, 42 female pts received EV as of Mar 3, 2023 (median follow-up, 11.8 mo). Median age was 53 y, 64% had ≥2L systemic tx for metastatic BC, and 33% had prior sacituzumab govitecan. ORR was 19.0%. Grade ≥3 tx-related adverse events (TRAEs) in >1 pt were decreased neutrophil count (n=3, 7%), decreased white blood cell count (n=2, 5%), and increased aspartate aminotransferase (n=2, 5%). Selected TRAEs of special interest were skin reactions (n=25, 60%), peripheral neuropathy (n=11, 26%), and hyperglycemia (n=2, 5%). In the HR+/HER2- BC cohort (median age, 57.0 y), 45 female pts received EV as of Dec 3, 2022 (median follow-up, 11.2 mo). Most (73%) had ≥3L systemic tx for metastatic BC. ORR was 15.6%. Grade ≥3 TRAEs in >1 pt were maculopapular rash (n=7, 16%), pruritus and increased aspartate aminotransferase (both n=3, 7%), and abdominal pain and erythema (both n=2, 4%). Selected TRAEs of special interest were skin reactions (n=28, 62%), peripheral neuropathy (n=12, 27%), and hyperglycemia (n=5, 11%). Additional efficacy data for both cohorts are in the table. Conclusions: EV showed antitumor activity in heavily pretreated TNBC. Safety in both cohorts was manageable and consistent with previous reports. Clinical trial information: NCT04225117 . [Table: see text]
Role of social determinants burden on outcomes and survival for AYAs with cancer.
Authors: Daunov Michael , Perez Jamie Abraham , Cullen Jennifer , Egler Rachel A. , Daunov Kate 
Published: May 2024

1610 Background: Health care utilization and survival are correlated with social determinants of health (SDoH). Minimal data exists on the impact of SDoH within AYA Oncology. Methods: TriNetX, a de-identified healthcare research database retrospectively examined presence of SDoH billing codes among AYA cancer patients at various time points. Three cohorts were evaluated: ages <15, 15-39, >39. Cox proportional hazards regression was used to assess predictors of SDoH burden and survival in AYAs. Results: Baseline demographics were similar across cohorts. AYAs had higher baseline SDoH (25811, 5.2%) compared to <15 (3913, 2.9%) and >39 (58237, 1.8%). After diagnosis, AYAs had greater incidence of SDoH burden at 1y (OR 1.86 vs <15, 2.71 vs >39), 3y (OR 1.79 vs <15, 2.63 vs >39), and 5y (OR 1.8 vs <15, 2.5 vs >39). AYAs with any SDoH had higher occurrences of ED (OR 2.51) and ICU visits (OR 1.94). Within AYAs, baseline SDoH code was most prevalent in 30-39 age group, males, Hawaiian/Pacific Islanders, and lung cancers. The most common SDoH code in AYAs at diagnosis was homelessness at 57.8%. In a multivariate analysis examining incidence of SDoH in AYAs, positive associations were age 30-39; 1.95 (1.61-2.37), males; 1.49 (1.36-1.63), American Indian/Alaska Native; 4.44 (3.12-6.31), and presence of SDoH at diagnosis; 83.0 (71.6-96.3). Mortality in AYAs was associated with age 30-39; 1.81 (1.72-1.91), males; 1.58 (1.54-1.63), unknown race; 1.53 (1.48-1.58), and CNS tumors; 1.15 (1.06-1.25). Conclusions: AYAs with cancer have a high prevalence of SDoH burden at diagnosis and acquired. Within AYAs, age 30-39, males, and minority populations were most likely to acquire a SDoH code and have worse survival. The strongest association with both incidence of SDoH burden and mortality was a SDoH code at diagnosis. [Table: see text]
Challenges and solutions to recruiting diverse populations to oncology clinical trials: A mixed-methods study of clinical research coordinators.
Authors: Velazquez Manana Ana I. , Trejo Evelin , Piawah Sorbarikor , Kaplan Celia 
Published: May 2024

1619 Background: Multiple barriers limit the enrollment of diverse populations in oncology clinical trials (CTs). A review of our institutional CTs recruitment dashboard identified underrepresentation of Black and Latinx adults among thoracic and gastrointestinal (GI) oncology CTs participants compared to demographics of our catchment area and patient population. We conducted a mixed-methods study to identify barriers and potential solutions to the enrollment of diverse populations in oncology CTs in our institution. Methods: We conducted a mixed methods study enrolling clinical investigators and clinical research coordinators’ (CRCs) at an NCI-designated CCC in Northern California. Data from CRCs is presented. All CRCs supporting CTs in the thoracic and GI medical oncology were invited to participate in qualitative, one-on-one, semi-structured interviews. Participants completed 60-90 minutes interview and a short survey. Data were analyzed using a thematic inductive approach. Results: Of 14 CRCs, the majority were female (78.6%), with primary focus on thoracic (50.0%) and GI (35.7%) oncology CTs. 64.3% of CRCs reported >80% of their work was dedicated to coordinating and managing therapeutic cancer CTs. In survey responses CRCs identified inability to take time away from work/family (64.3%), inadequate insurance coverage (42.9%), lack of transportation (35.7%), and language barriers (35.7%) as major barriers to enrollment of diverse patients in CTs. In qualitative interviews CRCs expressed the need of culturally and language appropriate materials for CT recruitment, establishing a sense of connection between clinical research staff/PI and patients, accommodating socioeconomic concerns, and resources to respond to potential participants’ mistrust of medical research. Main obstacles faced by CRCs during patient enrollment in CTs included lack of time, low patient awareness, resistance from colleagues, lack of multilingual staff, and inadequate logistical support. CRCs identified in-person interpretation as beneficial and identified a strong rapport between the clinical provider and the potential participant as the most important component to boost recruitment of minorities. Lastly, CRCs highlighted that institutional efforts are needed to increase CT participation among all populations. Conclusions: Lack of representation of diverse populations in CTs remains a complex challenge. Our study of CRCs’ perceptions highlights access to in-person translators, culturally and language concordant materials, education resources, and increased rapport as key areas for intervention to facilitate patient enrollment of diverse populations. Analysis into practice-specific patterns within our cancer centers can help identify areas for interventions to support the recruitment and enrollment of diverse populations in oncology CTs.
Evolution and prognostic significance of HER-2 changes from primary to residual disease in patients with HER-2–negative breast cancer receiving neoadjuvant chemotherapy.
Authors: Chen Xi , ji Lei , Qian Xiaoyan , Xiao Min , Li Qing , Li Qiao , Wang Jiayu , Fan Ying , Luo Yang , Ma Fei , Xu Binghe , Zhang Pin 
Published: May 2024

583 Background: HER-2 changes during the neoadjuvant chemotherapy has not been thoroughly evaluated. The current study aimed to analyze the HER-2 status changes from primary to residual disease in HER-2 negative patients after neoadjuvant chemotherapy and evaluate its impact in survival outcomes. Methods: HER-2 negative breast cancer patients with residual disease after NACT who had paired pre- and post-therapeutic HER2 testing results were retrospectively analyzed. Data on clinical and pathological characteristics, treatment information, and survival outcomes were collected for all eligible patients. HER2 changes from the primary to residual disease were described and logistic regression were performed to identify factors associated with HER2 changes. The Kaplan–Meier method and multivariate Cox regression were used for survival analysis. Results: 571 HER-2 negative breast cancer patients with residual disease after NACT were enrolled, including HER2-zero (35.2%, n=201) and HER2-low (64.8%, n=370) patients before NAC. The overall rate of HER-2 changes rate was 32.4% (negative to positive 1.1%, low to zero 15.4%, zero to low 15.9%). Among the patients with HER-2-zero before NAC, patients with HER-2 changes (zero to low) were likely to be hormone receptor positive (68.1% vs 36.7%, P<0.0001) and had a higher proportion of patients with Ki-67≤20 (Ki-67≤20 27.5% vs 15.6%, P=0.035). Among the patients with HER2-low before NAC, a higher proportion of hormone receptor negative were observed in HER2 changes patients (low to zero) (31.8% vs 18.4%, P=0.008) and the Ki-67 is relatively high in HER-2 changes patients (Ki-76 > 20 73.9% vs 65.0% P=0.030). Multivariable logistic regression analyses showed patients with hormone receptor positive before NAC were related to underwent HER2-zero transferring to HER2-low (OR, 3.436, P<0.0001). The median follow-up time was 50.0 months. In the HER-2 zero group, HER2 changes (zero to low) was significantly associated with better DFS comparing with constant HER2-zero (HR0.49, P=0.01) after adjustment, with 4-year DFS rate was 80.1%,55.7% (Log-rank P =0.033). Subgroup analysis showed that in the hormone receptor positive subgroup, patients with HER2 zero to low has a significant better DFS than patients with constant HER2-zero (Log-rank P=0.037). In the HER2-low group, no significant differences in survival outcomes between constant HER2-low and HER2 low to zero (HR1.07, P=0.778). Conclusions: HER2 status showed instability from primary tumor to residual disease after neoadjuvant treatment. HER2 changes (zero to low) was associated with better DFS in HER-2 zero patients.
Neoadjuvant chemotherapy as an indication to preserve nipple areolar complex in advanced breast cancer.
Authors: Alsafi Sarah , Kim Hee Jeong , Yoo Tae-Kyung , KIM Jisun , Lee Sae Byul , Chung Il Yong , Ko Beom Seok , Lee Jong Won , Sohn Byung Ho 
Published: May 2024

e12655 Background: Nipple areolar skin sparing mastectomy (NASSM) has similar oncologic and surgical safety compared to skin sparing mastectomy (SSM) and conventional mastectomy. It provides a superior cosmetic outcome, patient satisfaction and quality of life. With the increasing rate of pathological response rate with neoadjuvant chemotherapy (NAT), nipple preservation can be achieved. The aim of our study is to evaluate whether NASSM is an appropriate surgical procedure for patients in whom there is radiological evidence of extension or involvement of nipple areolar complex (NAC) prior to NAT. Methods: Patients with advanced breast cancer received neoadjuvant chemotherapy and NASSM or SSM between June 2006 and December 2021 at Asan Medical Center were retrospectively reviewed. We excluded patients with metastatic breast cancer on presentation, bilateral cancer and inflammatory breast cancer. Kaplan-Meier survival analysis and Cox proportional hazard models were applied to determine clinicopathological and radiological factors to determine NAC preservation. Our primary objective to assess tumor cells persistence in the NAC after radiological complete response or resolution of extension to NAC. Results: Total of 1,105 patients included. 71.7% of patients underwent NASSM and 17.2% SSM as a final operation. 144 patients (13%) had a change in the pre- NAT type of surgery decision. 83(7.5%) patients had nipple involvement on final pathology. Out of 312 patients who underwent SSM, only 76 patients had nipple involvement on final pathology When comparing patients who had nipple involvement to those who didn’t on final pathology, clinical T & N stage, histologic & nuclear grade, breast cancer subtype, presence of multifocality/multicentric disease on MRI pre or post NAT, distance of mass to NAC and mass size pre and post NAT, the presence of non mass extension to NAC post NAT, NAC thickening on any image pre and post NAT and presentation symptoms of nipple retraction and skin changes were statistically significant. A multivariate regression analysis was performed to compare all the above factors and showed that breast cancer subtype, tumor nipple distance on MRI pre NAT, nipple areolar thickening on MRI pre NAT, clinical response and nipple retraction on MMG post NAT were statistically significant and indicators of nipple involvement on final pathology. Only 8 patients developed NAC recurrence in the NASSM group. Conclusions: NASSM is a safe procedure in patients who had tumor extension to NAC prior to NAT and showed improvement post NAT as evident on MRI. Further prospective studies are needed to establish and criteria to preserve NAC in this subgroup of patients.