bluuebunny/crossref_metadata_2025_split huggingface dataset:
TACTIVE-K: Phase 1b/2 study of vepdegestrant, a proteolysis targeting chimera (PROTAC) estrogen receptor (ER) degrader, in combination with PF-07220060, a cyclin-dependent kinase (CDK)4 inhibitor, in ER+/human epidermal growth factor receptor 2 (HER2)- advanced breast cancer.
Authors: Telli Melinda L. , Gawryletz Chelsea D. , Wei Mei , Patnaik Amita , Lu Dongrui R. , Mazzoletti Marco , Valota Olga , Parmar Swapnil S , Tan Weiwei , Mukohara Toru 
Published: June 2024

TPS1131 Background: Vepdegestrant (ARV-471) is an investigational, orally administered PROTAC ER degrader. Initial results from a phase 1b cohort of a first-in-human phase 1/2 study (NCT04072952) showed that vepdegestrant, in combination with the CDK4/6 inhibitor palbociclib, had robust clinical activity (clinical benefit rate [CBR]: 63.0%) in heavily pretreated patients (pts) with ER+/HER2- advanced breast cancer. PF-07220060 is an investigational CDK4-selective inhibitor, which in contrast to CDK4/6 inhibitors, spares CDK6 blockade and demonstrates less neutropenia in in vivo models. A first-in-human phase 1/2a study (NCT04557449) demonstrated promising antitumor activity with PF-07220060 in pts with advanced solid tumors with a CBR of 52.4%. Preclinical tumor models have shown that vepdegestrant + PF-07220060 effectively suppresses tumor growth to a greater extent than either agent alone. This open-label, multicenter phase 1b/2 study (NCT06206837) will evaluate the combination of vepdegestrant + PF-07220060 in pts ≥18 y with confirmed ER+/HER2- advanced breast cancer. Methods: The phase 1b portion will use an escalation/de-escalation approach to determine the recommended phase 2 dose (RP2D) of the combination of vepdegestrant and PF-07220060. The phase 2 portion will further evaluate the preliminary antitumor activity, safety, and pharmacokinetics (PK) of the combination at the RP2D. Pts (N≈65) will receive vepdegestrant orally once daily continuously and PF-07220060 orally twice daily continuously. The primary endpoint of the phase 1b portion is the number of pts with dose-limiting toxicities; secondary endpoints are antitumor activity (objective response rate [ORR], duration of response [DOR], CBR), progression-free survival (PFS), safety, and PK. The primary endpoint of the phase 2 portion is ORR; secondary endpoints are antitumor activity (DOR, CBR), PFS, safety, plasma concentrations of study drugs, and changes in circulating tumor DNA. Previously presented at ESMO Breast Cancer 2024, FPN: 264TiP, M Telli, et al. Reused with permission. Clinical trial information: NCT06206837 .
Innovation of the first-line strategy optimized as abemaciclib with endocrine therapy based on the ESR1mutation of ctDNA for patients with HR-positive HER2-negative advanced metastatic breast cancer (JBCRG-M08; AMBER study).
Authors: Yoshinami Tetsuhiro , Sasada Shinsuke , Nishimura Meiko , Iwase Madoka , Oshiro Chiya , Terata Kaori , Ishihara Mikiya , Bando Hiroko , Tanabe Masahiko , Yoshimoto Nobuyasu , Akiyoshi Sayuri , Takada Masahiro , Ishiguro Hiroshi , Saji Shigehira , Morita Satoshi , Masuda Norikazu 
Published: June 2024

TPS1134 Background: Aromatase inhibitor (AI) + CDK4/6 inhibitor (CDK4/6i) has been established as a standard of care of 1st line treatment for hormone receptor (HR)-positive/HER2-negative advanced metastatic breast cancer (AMBC). ESR1 mutations are considered to be one of the causes of acquiring resistance against the AI +CDK4/6i. PADA-1 trial showed that replacing AI with fulvestrant (FUL) as a partner of palbociclib (PAL) at occurrence of some ESR1 mutations improved progression-free survival (PFS) and PFS2, suggesting PAL should be used based on the strategy of selecting endocrine agents according to ESR1 mutation status by ctDNA analysis. On the other hand, we don’t know if this strategy is effective in the case of abemaciclib (ABM), another CDK4/6i established as the standard of care for AMBC. We are conducting a study to make evidence on this clinical question. Methods: This multicenter, single-arm phase II study is designed to evaluate the efficacy and safety of the strategy to replace AI with FUL for detectable ESR1 mutations in combination with ABM. Key eligibility criteria include patients receiving AI+ABM for at least 6 months as first-line treatment for HR-positive/ HER2-negative AMBC without progressive disease (PD). While continuing AI+ABM, ctDNA analysis will be performed at approximately 3, 9, 15 months from enrollment. If ESR1 mutation is identified at any point and non-PD is confirmed by CT, FUL+ABM will be initiated instead of AI+ABM. In patients with ESR1 mutations completely cleared by ctDNA analysis 6 months after the start of FUL+ABM, AI+ABM will be resumed (Re-AI+ABM arm); the Re-AI+ABM arm is intended to investigate whether the discontinuation of FUL will allow clones with ESR1 mutations to proliferate again. Primary endpoint is 2-year PFS rate in full analysis set. Key secondary endpoints include 2-year PFS rate by treatment sequences, and rate of disappearance of ESR1mutations in ctDNA with FUL+ABM. Plasma-SeqSensei Breast Cancer IVD Kit, which can simultaneously detect mutations in a wide range of six genes including ESR1, as well as PIK3CA, AKT1, ERBB2, KRAS, and TP53, is used for ctDNA analysis in this study. Based on PFS data in MONARCH3 study, the threshold and expected value of the 2-year PFS rate were estimated to be 45% and 55%, respectively, and target sample size was calculated as 160 patients. Patient enrollment started in December 2022 and run through December 2024; as of December 2023, 54 patients have been enrolled. Clinical trial information: 051220133.
Phase I/II study of stereotactic radiation and sacituzumab govitecan with zimberelimab in the management of metastatic triple negative breast cancer with brain metastases.
Authors: Ahmed Kamran A. , Kim Youngchul , DeJesus Michelle , Oliver Daniel Eli , Mills Matthew , Nair Rajesh , Armaghani Avan J. , Costa Ricardo L , Lee Kimberley T , Loftus Loretta S. , O'Connor Tracey L. , Soliman Hatem Hussein , Soyano Muller Aixa Elena , Vogelbaum Michael A. , Forsyth Peter A. J. , Arrington John , Rosa Marilin , Yu Michael , Han Hyo S. 
Published: June 2024

TPS1140 Background: Patients with triple negative breast cancer (TNBC) are at a high risk to develop brain metastases. The prognosis and quality of life for triple negative brain-metastatic breast cancer remains very poor. Treatment options are limited and improvement in efficacy is needed. Sacituzumab govitecan (SG) has shown blood brain barrier (BBB) penetration in preclinical and clinical settings with anti-tumor activity in the phase III ASCENT Trial (NCT02574455). Radiotherapy can open the BBB and has been shown to be safe in combination with anti-PD-1 therapy in our previous trial (NCT03807765). Therefore, combining radiation with the anti-PD-1 monoclonal antibody, zimberelimab, and SG may provide a synergistic anti-tumor approach. We hypothesize the use of SG and zimberelimab with stereotactic radiosurgery (SRS) among patients with metastatic TNBC with brain metastases will be safe and improve progression free survival compared to treatment with SG alone. Methods: The study is designed as a single-arm, nonrandomized, open-label, phase I/II trial of SG and zimberelimab with SRS among patients with metastatic TNBC with brain metastases. The primary endpoint will be neurologic toxicity defined by CTCAE v5 criteria (phase I) and 12 month PFS (phase II). TNBC patients ≥ 18 years old with ≤ 15 brain metastases with at least one measurable lesion ≥ 0.5 cm per RANO-BM criteria will be enrolled. Treatment will be initiated with SRS followed 1 week later by SG on days 1 and 8 (10 mg/kg) with zimberelimab on day 1 (360 mg IV) repeated every 3 weeks. Follow-up imaging response assessments will be conducted at q9 week intervals. An interim analysis will be performed after 21 patients are enrolled. An additional 10 patients will be enrolled if interim futility criteria are not met. Clinical trial information: NCT06238921 .
Dose/Exposure Relationship of Exercise and Distant Recurrence in Primary Breast Cancer
Authors: Soldato Davide , Michiels Stefan , Havas Julie , Di Meglio Antonio , Pagliuca Martina , Franzoi Maria Alice , Pistilli Barbara , Iyengar Neil M. , Cottu Paul , Lerebours Florence , Coutant Charles , Bertaut Aurélie , Tredan Oliver , Vanlemmens Laurence , Jouannaud Christelle , Hrab Iona , Everhard Sibille , Martin Anne-Laure , André Fabrice , Vaz-Luis Ines , Jones Lee W. 
Published: June 2024

PURPOSE
Postdiagnosis exercise is associated with lower breast cancer (BC) mortality but its link with risk of recurrence is less clear. We investigated the impact and dose-response relationship of exercise and recurrence in patients with primary BC.

METHODS
Multicenter prospective cohort analysis among 10,359 patients with primary BC from 26 centers in France between 2012 and 2018 enrolled in the CANcer TOxicities study, with follow-up through October 2021. Exercise exposure was assessed using the Global Physical Activity Questionnaire-16, quantified in standardized metabolic equivalent of task–hours per week (MET-h/wk). We examined the dose/exposure response of pretreatment exercise on distant recurrence-free interval (DRFI) for all patients and stratified by clinical subtype and menopausal status using inverse probability treatment weighted multivariable Cox models to estimate hazard ratios (HRs).

RESULTS
For the overall cohort, the relationship between exercise and DRFI was nonlinear: increasing exercise ≥ 5 MET-h/wk was associated with an inverse linear reduction in DRFI events up to approximately 25 MET-h/wk; increasing exercise over this threshold did not provide any additional DRFI benefit. Compared with <5 MET-h/wk, the adjusted HR for DRFI was 0.82 (95% CI, 0.61 to 1.00) for ≥ 5 MET-h/wk. Stratification by subtype revealed the hormone receptor–/human epidermal growth factor receptor 2– (HR–/HER2–; HR, 0.59 [95% CI, 0.38 to 0.92]) and HR–/HER2+ (HR, 0.37 [95% CI, 0.14 to 0.96]) subtypes were preferentially responsive to exercise. The benefit of exercise was observed especially in the premenopausal population.

CONCLUSION
Postdiagnosis/pretreatment exercise is associated with lower risk of DRFI events in a nonlinear fashion in primary BC; exercise has different impact on DRFI as a function of subtype and menopausal status.
Challenges in Diagnosing and Managing the Spectrum of Primary Aldosteronism
Authors: Yang Jun , McCarthy Josephine , Shah Sonali S , Ng Elisabeth , Shen Jimmy , Libianto Renata , Fuller Peter J 
Published: June 2024

Abstract
Primary aldosteronism, characterized by the dysregulated production of aldosterone from 1 or both adrenal glands, is the most common endocrine cause of hypertension. It confers a high risk of cardiovascular, renal, and metabolic complications that can be ameliorated with targeted medical therapy or surgery. Diagnosis can be achieved with a positive screening test (elevated aldosterone to renin ratio) followed by confirmatory testing (saline, captopril, fludrocortisone, or oral salt challenges) and subtyping (adrenal imaging and adrenal vein sampling). However, the diagnostic pathway may be complicated by interfering medications, intraindividual variations, and concurrent autonomous cortisol secretion. Furthermore, once diagnosed, careful follow-up is needed to ensure that treatment targets are reached and adverse effects, or even recurrence, are promptly addressed. These challenges will be illustrated in a series of case studies drawn from our endocrine hypertension clinic. We will offer guidance on strategies to facilitate an accurate and timely diagnosis of primary aldosteronism together with a discussion of treatment targets which should be achieved for optimal patient outcomes.
Neuropsychological Test Performance Differentiates Subgroups of Individuals With Adult Moyamoya Disease: A Cross-Sectional Clinical Study
Authors: DeDios-Stern Samantha L. , Gotra Milena Y. , Resch Zachary J. , Jennette Kyle J. , Amin-Hanjani Sepideh , Charbel Fady T. , Alaraj Ali , Testai Fernando D. , Thulborn Keith R. , Vargas Alejandro , Pliskin Neil H. , Soble Jason R. 
Published: June 2024

BACKGROUND AND OBJECTIVES:
Moyamoya disease (MMD) is a rare noninflammatory disorder involving progressive intracranial vasculopathy and impaired cerebral blood flow in the anterior circulation, resulting in stroke and cognitive impairment. We aimed to characterize cognitive impairment and the possible predictive value of sociodemographic and clinical characteristics of adults with MMD.

METHODS:
This cross-sectional study examined neurocognitive performance in a group of 42 consecutive adult patients (mean age = 40.52 years; 69% female) referred for a presurgical neuropsychological evaluation. Neuropsychological functioning was assessed with a comprehensive battery, and cognitive dysfunction was defined as 1.5 SDs below the mean. Neurocognitive performance correlated with clinical/demographic characteristics and disease markers.

RESULTS:
Most patients (91%) had a history of stroke, and 45% had cognitive deficits, most notably on measures of attention/speed (48%), executive functioning (47%), visuoconstruction (41%), and memory (31%-54%). Only higher educational attainment and poor collateral blood flow in the right hemisphere differentiated cognitively impaired (n = 19) and intact groups (n = 23), and MMD-related characteristics (eg, disease duration, stroke history) did not differentiate the 2 groups.

CONCLUSION:
Consistent with previous work, frontal-subcortical cognitive deficits (eg, deficits in mental speed, attention, executive functioning) were found in nearly half of patients with MMD and better cognitive performance was associated with factors related to cognitive reserve. Angiographic metrics of disease burden (eg, Suzuki rating, collateral flow) and hemodynamic reserve were not consistently associated with poorer cognitive outcomes, suggesting that cognition is a crucial independent factor to assess in MMD and has relevance for treatment planning and functional status.
Staying in the Game: Interventions for Managing Achilles Tendinopathy in the In-Season Athlete
Authors: Dyrek Paige , Tsitsilianos Nicholas , McInnis Kelly C. , Tenforde Adam S. , Borg-Stein Joanne 
Published: June 2024

Abstract
Achilles tendinopathy is a common overuse injury that is traditionally managed with activity modification and a progressive eccentric strengthening program. This narrative review describes the available evidence for adjunctive procedural interventions in the management of midportion and insertional AT, specifically in the athletic population. Safety and efficacy data from available literature on extracorporeal shockwave therapy, platelet-rich plasma, high-volume injectate with or without tendon scraping, and percutaneous needle tenotomy are used to propose an algorithm for treatment of Achilles tendinopathy for the in-season athlete.
Analysis of Common Exercise Modalities in Improving Athletic Performance in Older Adults: A Narrative Review
Authors: Nguyen Chantal , Kaufman Matthew , Vallejo Adrian , DeParis Sarah , Friedlander Anne , Frehlich Levi , Fredericson Michael 
Published: June 2024

Abstract
Exercise leads to robust cardiovascular, musculoskeletal, and psychological benefits that improve quality of life and longevity for older adults, but accompanying improvements in athletic parameters are less well explored. The aim of this review is to summarize some of the most common exercise modalities, namely, Pilates, martial arts (tai chi, Japanese-style karate, hard martial arts), locomotion (brisk walking/jogging and running), Masters sports, resistance training, and high-intensity interval training, in improving athletic performance for older adults. Regular participation in these activities can have robust yet unique impacts on physical performance that prolong exercise participation. In particular, this review will explore benefits in cardiorespiratory fitness, power, strength, flexibility, and balance, thereby hopefully improving endurance, exercise adherence, and overall fall risk. A narrative literature review was performed to explore benefits, pitfalls, and recommendations for some of the most popular exercise modalities for older adults.
Psoriatic arthritis - Tofacitinib as a new treatment
Authors: Skorupska Marta , Czeczotka Magdalena Joanna , Martka Martyna Magdalena , Popławska Natalia Aleksandra , Śliz Justyna , Woźniak Krzysztof 
Published: June 2024

Introduction:
JAK inhibitors are used in the treatment of psoriatic arthritis when there is a lack of effective response or intolerance to first-line drugs or their use must be discontinued due to the presence of side effects. JAK inhibitors inhibit the JAK-STAT signaling pathway which plays a significant role in the pathogenesis of many inflammatory and autoimmune diseases. This mechanism leads to a reduction in the level of pro-inflammatory cytokines which causes rapid improvement in the patient's clinical condition. Tofacitinib is the best-known drug in this group; its use carries an increased risk of cardiovascular events and reactivation of the varicella-zoster virus. Regular monitoring of patients results in faster detection of the first signs of undesirable effects and the cessation of their progression. The drug's safety profile is acceptable and the benefits outweigh possible complications.

Aim of the study:

The aim of the study is to summarize the available knowledge about tofacitinib treatment in psoriatic arthritis. The way of work, effectiveness of treatment and potential side effects were summarized and described.

Materials and methods:

The literature available in PubMed database was reviewed using the following keywords:
“Psoriatic arthritis”, “Tofacitinib”, “JAK inhibitors”, “JAK-STAT”

Conclusion:

Tofacitinib treatment in rheumatology is used in psoriatic arthritis. The rapid improvement in the clinical condition of patients treated with JAK inhibitors is due to their direct impact on the modulation of the pathogenesis of the disease. The predictable benefits of therapy outweigh the side effects which can be detected at an early stage with regular monitoring of the patient.
Precise Classification, and Accurate Diagnosis: Key Elements for Effective Treatment and Management of Headache Disorders
Authors: Otręba Karina , Czupryńska Karolina , Czyżniewska Oliwia , Domański Mikołaj , Kopczyńska Barbara , Szałajska Julia , Wierzejska Natalia , Wojcieszek Maria 
Published: June 2024

Introduction
Tension-type headaches (TTH) are a significant health concern that demands precise diagnostic approaches and effective management strategies. A nuanced understanding of their pathophysiology and diagnostic challenges is not just pivotal, but a responsibility we share, for enhancing patient care.
Aim
This article aims to explore the complex realm of TTH diagnosis and management, underlining the need for precision in diagnostics and the intricate balance of cost-effectiveness. It also delves into the diverse therapeutic options available for treating TTH, presenting a stimulating challenge for healthcare professionals, researchers, and medical students.
State of Knowledge
Initial diagnosis involves excluding secondary headaches by identifying red flags indicative of serious underlying conditions. A detailed medical history, complemented by patient-recorded pain diaries, enhances diagnostic accuracy. Ancillary procedures like neuroimaging, despite cost-effectiveness debates, are often preferred by clinicians to mitigate diagnostic risks. Validated tools such as the MIDAS and HIT-6 questionnaires provide valuable insights into headache-related disability. Differential diagnosis among headache types relies on recognizing distinctive clinical features.
Summary (Conclusions)
Effectively managing TTH necessitates a multifaceted approach, incorporating pharmacological, non-pharmacological, and lifestyle interventions tailored to individual patient needs. Collaborative efforts spanning legal, technological, and research domains are crucial for advancing headache diagnostics and therapeutics. While technological advancements offer promise, interdisciplinary collaboration remains fundamental in optimizing patient care outcomes.
Clinical comprehensive treatment protocol for managing diabetic foot ulcers: A retrospective cohort study
Authors: Wang Yan-Bin , Lv Yan , Li Guang-Yu , Zheng Ji-Ting , Jiang Qing-Xin , Wei Ran 
Published: June 2024

BACKGROUND
Diabetic foot ulcers (DFUs) are a common complication of diabetes, often leading to severe infections, amputations, and reduced quality of life. The current standard treatment protocols for DFUs have limitations in promoting efficient wound healing and preventing complications. A comprehensive treatment approach targeting multiple aspects of wound care may offer improved outcomes for patients with DFUs. The hypothesis of this study is that a comprehensive treatment protocol for DFUs will result in faster wound healing, reduced amputation rates, and improved overall patient outcomes compared to standard treatment protocols.
AIM
To compare the efficacy and safety of a comprehensive treatment protocol for DFUs with those of the standard treatment protocol.
METHODS
This retrospective study included 62 patients with DFUs, enrolled between January 2022 and January 2024, randomly assigned to the experimental (n = 32) or control (n = 30) group. The experimental group received a comprehensive treatment comprising blood circulation improvement, debridement, vacuum sealing drainage, recombinant human epidermal growth factor and anti-inflammatory dressing, and skin grafting. The control group received standard treatment, which included wound cleaning and dressing, antibiotics administration, and surgical debridement or amputation, if necessary. Time taken to reduce the white blood cell count, number of dressing changes, wound healing rate and time, and amputation rate were assessed.
RESULTS
The experimental group exhibited significantly better outcomes than those of the control group in terms of the wound healing rate, wound healing time, and amputation rate. Additionally, the comprehensive treatment protocol was safe and well tolerated by the patients.
CONCLUSION
Comprehensive treatment for DFUs is more effective than standard treatment, promoting granulation tissue growth, shortening hospitalization time, reducing pain and amputation rate, improving wound healing, and enhancing quality of life.