bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk Factors for Early Treatment Discontinuation Due to Toxicity Among Patients With Metastatic Castration-resistant Prostate Cancer Receiving Androgen Receptor–targeted Therapy
Authors: Chakrani Zakaria , Mellgard George , Saffran Nathaniel , McCroskery Stephen , Taylor Nicole , Patel Mann , Liaw Bobby , Galsky Matthew , Oh William K. , Tsao Che-Kai , Patel Vaibhav G. 
Published: February 2024

Background:
Androgen receptor–targeted therapies (ARTs) improve survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC); however, a significant portion of patients discontinue treatment for various reasons including treatment-related toxicity. We aim to describe reasons for ART treatment discontinuation and identify predictors associated with increased risk of treatment discontinuation due to toxicity.

Methods:
We performed a single-institution retrospective review of patients with mCRPC receiving ART between 2010 and 2021. Our primary aim was to identify risk factors for treatment discontinuation due to toxicity. Our secondary aim was to describe ART discontinuation patterns among patients with mCRPC.

Results:
One hundred thirty-three patients with mCRPC started and discontinued ARTs. Fourteen patients (10.5%) discontinued treatment due to toxicity. Common reasons for treatment discontinuation include Prostate Specific Antigen test progression, radiographic progression, toxicity, and death. Significant predictors of treatment discontinuation due to toxicity on bivariate analysis and multivariate analysis included patient-reported falls (odds ratio [OR]: 7.67, CI: [1.31-40.42]; P=0.016), rash (OR: 13.4, CI: [1.35-134.81]; P=0.026), and weakness (OR: 4.16, CI: [1.15-15.0]; P=0.019).

Conclusions:
Our work presents the first description of ART treatment discontinuation and its causes in the real-world setting, as well as patient-reported side effects. Most patients with mCRPC discontinued treatment due to the progression of disease and a minority of patients discontinued secondary to treatment toxicity. Initial multivariable analysis suggests that patient-reported weakness, falls, and rash were associated with a higher likelihood of treatment discontinuation due to toxicity. Early monitoring of this population can prolong the duration of treatment and prevent unnecessary treatment burden.
Ultrasound-guided Treatment of Polycaprolactone Granuloma
Authors: Cerón Bohórquez Jair Mauricio , Desyatnikova Stella 
Published: February 2024

Summary:
Foreign body granulomas associated with polycaprolactone (PCL) filler injections are rare, yet challenging to manage. Multiple management modalities have been described. Here, we present a literature review and describe a case of histologically confirmed PCL-related granuloma, treated using ultrasound-guided injections of triamcinolone, hyaluronidase, and 5-fluorouracil combined with oral prednisolone and doxycycline.
Accelerated Corneal Crosslinking to Arrest Progression of Corneal Ectasia: A Prospective Multicenter Study
Authors: Salvador-Culla Borja , Afsara Ahmmed , Roper Nicola , Mulroy Julie , Galankova Lubomira , Duncan Holly , Tabibian David , Lamarca-Mateu Jose , Figueiredo Francisco C. 
Published: February 2024

Objectives:
To report the results of epithelium-off accelerated corneal collagen crosslinking (accelerated corneal crosslinking [ACXL]) in patients with progressive keratoconus.

Methods:
This prospective, nonrandomized, noncomparative, interventional, multicenter clinical study included all patients who underwent ACXL, either continuous (c-ACXL; 9 mW/cm2, 10′, 5.4 J/cm2) or pulsed (p-ACXL; 2″ON/1″OFF, 30 mW/cm2, 4.5′, 5.4 J/cm2) between January 2014 and May 2017. Best-corrected visual acuity, sphere, cylinder, spherical equivalent, and topographical keratometry data were collected preoperatively and at 1, 3, 6, 12, 18, and 24 months postoperatively.

Results:
Ninety-six eyes of 78 patients were included. The mean age was 20.8±4.4 years (14–33) for c-ACXL and 26.7±7.7 years (12–37) for p-ACXL. The mean best-corrected visual acuity was 0.4±0.4 for c-ACXL and 0.01±0.1 for p-ACXL preoperatively, and 0.3±0.3 (P=0.0014) and −0.01±0.1 (P=0.1554), respectively, at the last follow-up. The subjective sphere and spherical equivalent did not show statistically significant differences between the time points (P>0.05). The subjective cylinder showed significant differences (P=0.0013 for c-ACXL; P=0.0358 for p-ACXL). Keratometric values (Ksteep, Kflat, and SimK) remained stable, with no statistically significant differences (P>0.05). No major complications were noted.

Conclusions:
Both c-ACXL and p-ACXL are equally safe and effective ACXL protocols in stabilizing the progression of keratoconus and can be considered alternatives to the conventional Dresden protocol.
Enhanced durability and evolution of retreatment criteria of intravitreal antivascular endothelial growth factor agents for diabetic macular edema
Authors: Mandava Nikhil K. , Kuriyan Ajay E. , Ho Allen C. , Hsu Jason , Regillo Carl D. , Klufas Michael A. 
Published: February 2024

Purpose of review
The increasing prevalence of diabetic macular edema (DME) necessitates an updated review of treatment modalities. While the shift from laser to anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed patient outcomes, benefits of these agents are not fully realized in real-world implementation relative to the setting of controlled clinical trials. This review outlines the evolution of intravitreal anti-VEGF treatment extension protocols for DME that reflect efforts to address treatment adherence challenges while optimizing visual outcomes.

Recent findings
Recent studies highlight the efficacy of extended-interval dosing with anti-VEGF agents in managing DME. Trials such as RISE/RIDE, VISTA/VIVID, and LUCIDATE have established the foundation of these regimens by demonstrating sustained visual gains with continuous treatment. However, newer trials including PROTOCOL T, KESTREL/KITE, YOSEMITE/RHINE, and PHOTON have furthered this concept, revealing that less frequent dosing of various anti-VEGF agents can maintain similar visual acuity and anatomical outcomes to traditional monthly injections.

Summary
The reviewed findings suggest a paradigm shift in DME treatment toward less frequent anti-VEGF injections. This has significant implications for clinical practice, potentially leading to greater adherence to treatment regimens and sustained visual function in patients, while minimizing treatment burden and healthcare costs. Further investigation into the long-term effects of extended dosing intervals is required.
Musculoskeletal pain in 13-year-old children: the generation R study
Authors: van Leeuwen Guido J. , van den Heuvel Marleen M. , Bindels Patrick J. E. , Bierma-Zeinstra Sita M. A. , van Middelkoop Marienke 
Published: February 2024

Abstract
Musculoskeletal (MSK) pain is a common reason for consultation in general practice and frequently reported in children and adolescents. This study examined the prevalence of MSK pain in 13-year-old children and assessed associations with physical and psychosocial factors. Data from the Generation R Study, a population-based birth cohort, was used. Prevalence and characteristics of MSK pain were assessed, using a pain mannequin, at 13 years of age (N = 3062). Demographics and data on physical activity, sedentary behaviors, previous reported MSK pain, and behavioral problems were extracted from questionnaires. The body mass index (BMI) SD-score was calculated from objectively measured weight and height. A prevalence of 23.3% was found for MSK pain in children of which 87.2% persisted for more than 3 months (ie, chronic), 45.5% experienced pain daily. More physically active children and children with a higher BMI reported MSK pain more frequently compared with non-MSK pain and no pain. The knee was the most often reported location. Children with MSK pain were more likely to have reported MSK pain at 6 years. Multivariable analyses showed significant associations for male sex (OR 0.74, 95% CI 0.56-0.98), high maternal educational (OR 0.69, 95% CI 0.49-0.96), higher BMI (OR 1.19, 95% CI 1.05-1.35), being physically active (OR 1.41, 95% CI 1.03-1.91), and behavioral problems (OR 1.85, 95% CI 1.33-2.59) with the presence of MSK pain. The chronic nature of MSK pain in combination with the relatively high prevalence of MSK pain in this study shows that MSK pain is already an important problem at a young age.
A Systematic Review of Variables Used in Physical Therapist Education Program Admissions Part 2: Noncognitive Variables
Authors: Bowens Andrea N. 
Published: February 2024

Background and Purpose.
Physical therapist (PT) education professionals agree on promoting holistic admissions practices to increase student body diversity but lack consensus about what factors in an application should be part of this process. This systematic literature review aimed to understand the value of noncognitive variables in PT education admissions.

Methods.
The initial literature search identified 1,592 articles in databases and relevant journals. Of the 39 studies meeting the inclusion criteria, 29 reported on noncognitive variables.

Results.
Commonly used noncognitive variables (interviews, written essays, letters of recommendation, and clinical experiences) were insignificant or inconsistently associated with performance in the PT program or on the National Physical Therapy Examination. Sociodemographic variables appeared to negatively affect the academic qualifications of applicants who were older, identified with underrepresented racial/ethnic groups, and reported English as a second language. Finally, 5 studies identified personal attributes, such as emotional intelligence and grit, as having a significant relationship with successful student outcomes.

Discussion and Conclusion.
Cognitive variables should serve as only one of several factors considered in admissions to achieve a more diverse class of students. Physical therapist education programs may use this evidence to reevaluate their admissions practices to include a balanced consideration of cognitive and noncognitive variables.
Lipschütz ulcers due to SARS-CoV-2 infection: a neglected diagnosis in emergency room
Authors: Brambilla Ilaria , Bolcato Vittorio , Volonté Martina , Querzani Andrea , Guarracino Carmen , Tondina Enrico , Marseglia Gian Luigi , Brazzelli Valeria 
Published: February 2024

Background:
Primary acute genital ulcers, or Lipschütz ulcers (LU), are nonsexually transmitted, painful, self-limiting, nonrecurrent vulvar ulcers with unclear pathogenesis, representing a challenging diagnosis in emergency setting. LU have recently been described in association with severe acute respiratory syndrome coronaVirus 2 (SARS-CoV-2) infection and vaccination.

Objective:
The aim of this study is to describe 2 cases of LU due to SARS-CoV-2 infection, highlighting the diagnostic process, differential diagnosis, disease course, and management options.

Methods:
We describe 2 young females (12 and 9 years old) who presented to pediatric emergency room with the sudden onset of well-demarcated, painful, vulvar ulcers with fibrinous necrotic center.

Results:
Both patients tested positive to SARS-CoV-2 nasal swab, and, at physical examination, no other lesions were found in other cutaneous or mucosal sites. Sexual abuse was excluded in both cases, as well as infectious and autoimmune diseases. Supportive analgesic therapy was administered, and complete remission of lesions was observed at follow-up visits without evidence of scarring.

Limitations:
The main limitation of this work is represented by the small number of cases described.

Conclusion:
Even though extremely rare, LU related to COVID-19 are an emerging entity to be considered in the diagnosis of acute genital ulcerations. Multidisciplinary diagnostic workup of genital ulcers must be established in order to exclude sexual child abuse, to ensure patient safety, and to avoid unnecessary treatment and familial anxiety.
Novel indications for referral and care for simultaneous liver kidney transplant recipients
Authors: Lum Erik L. , Bunnapradist Suphamai , Wiseman Alexander C. , Gurakar Ahmet , Ferrey Antoney , Reddy Uttam , Al Ammary Fawaz 
Published: February 2024

Purpose of review
Kidney dysfunction is challenging in liver transplant candidates to determine whether it is reversible or not. This review focuses on the pertinent data on how to best approach liver transplant candidates with kidney dysfunction in the current era after implementing the simultaneous liver kidney (SLK) allocation policy and safety net.

Recent findings
The implementation of the SLK policy inverted the steady rise in SLK transplants and improved the utilization of high-quality kidneys. Access to kidney transplantation following liver transplant alone (LTA) increased with favorable outcomes. Estimating GFR in liver transplant candidates remains challenging, and innovative methods are needed. SLK provided superior patient and graft survival compared to LTA only for patients with advanced CKD and dialysis at least 3 months. SLK can provide immunological protection against kidney rejection in highly sensitized candidates. Post-SLK transplant care is complex, with an increased risk of complications and hospitalization.

Summary
The SLK policy improved kidney access and utilization. Transplant centers are encouraged, under the safety net, to reserve SLK for liver transplant candidates with advanced CKD or dialysis at least 3 months while allowing lower thresholds for highly sensitized patients. Herein, we propose a practical approach to liver transplant candidates with kidney dysfunction.
A Predictive Strategy for Nonsurgical Management of Pancreatic Stones
Authors: Yamamoto Satoshi , Inui Kazuo , Katano Yoshiaki , Miyoshi Hironao , Kobayashi Takashi , Tachi Yoshihiko 
Published: February 2024

Objectives
We set out to predict whether nonsurgical treatment is likely to succeed in removing pancreatic stones in a given patient and also to determine an optimal maximal number of extracorporeal shock wave lithotripsy (ESWL) sessions for treatment of pancreatolithiasis in that patient.

Materials and Methods
We ascertained the number of ESWL sessions for each of 164 patients undergoing that treatment for pancreatolithiasis between 1992 and 2020. Median follow-up duration was 31 months (range, 0–239), median age was 58 years (22–83), and the male to female ratio was 5.1:1.0. Patients were divided into 2 groups based upon an optimal maximal number of ESWL sessions determined by receiver operating characteristic analysis.

Results
Total stone clearance was achieved in 130 of 164 patients (79%). The median number of ESWL sessions was 3 (1–61). Receiver operating characteristic analysis determined 7 to be the optimal maximal number of sessions. Complete clearance was more frequent (87%) among the 131 patients requiring 7 or fewer ESWL sessions than among the 33 undergoing more (48%, P < 0.001). Seventeen patients (52%) undergoing 8 or more sessions still had residual stones.

Conclusions
If any pancreatic stones persist after 7 ESWL sessions, we recommend transition to medical or surgical treatments.
Cognitive flexibility training for chronic pain: a randomized clinical study
Authors: Holzer Katherine J. , Todorovic Marko S. , Wilson Elizabeth A. , Steinberg Aaron , Avidan Michael S. , Haroutounian Simon 
Published: February 2024

Abstract

Introduction:
Previous studies suggest an association between cognitive flexibility and development of chronic pain after surgery. It is not known whether cognitive flexibility can be improved in patients with chronic pain.

Objectives:
This study tested whether a neurocognitive training program results in improved cognitive flexibility and pain in patients with chronic pain.

Methods:
We conducted a single-center, prospective, randomized study investigating 5-week daily neurocognitive training in patients with chronic pain. Participants (n = 145) were randomized into neurocognitive training or care as usual, and they completed assessments at baseline, posttreatment, and 3 months. The treatment group was asked to spend 35 minutes daily completing a program with tasks on cognitive flexibility, memory, attention, and speed. The primary outcome was performance on the neurocognitive performance test (NCPT). Secondary outcomes included levels of pain interference and severity.

Results:
At 5 weeks, the treatment group showed greater improvements on NCPT compared with the control group (d = 0.37); effect size was smaller at 3 months (d = 0.18). The treatment group reported lower pain severity at 5 weeks (d = 0.16) and 3 months (d = 0.39) than the control group, but pain interference was only lower at 3 months (d = 0.20).

Conclusions:
Outcomes suggest that using neurocognitive training to modify cognitive flexibility in patients with chronic pain may improve pain severity. This study provided effect size estimates to inform sample size calculations for randomized controlled trials to test the effectiveness of neurocognitive interventions for the prevention and treatment of chronic pain.
The role of cytokines and chemokines in the maintenance of chronic pain—a pilot study
Authors: Lassen Josephine , Leypoldt Frank , Hüllemann Philipp , Janssen Maren , Baron Ralf , Gierthmühlen Janne 
Published: February 2024

Abstract

Introduction:
The immune system is believed to be important in the initiation and maintenance of chronic pain.

Objectives:
The aim was to investigate whether patients with chronic painful polyneuropathy (PP) differ in cytokine profiles of serum and/or cerebrospinal fluid (CSF) compared with pain-free controls.

Methods:
Thirty-nine patients (16 women and 23 men, mean age, 69.2 ± 12.7 years, range 41–92 years) with PP (mean duration 43 ± 48.3 months) were phenotyped with quantitative sensory testing and electroneurography, and serum and CSF samples were analyzed by 40-multiplexed, bead-based cytokine immunoassays. Results were compared with 36 age- and gender-matched patients with normal pressure hydrocephalus and absence of abnormal CSF findings.

Results:
Compared with controls, patients with PP had lower concentrations of several proinflammatory and anti-inflammatory chemokines and cytokines in CSF, and others showed the same tendency, among these were tumor necrosis factor-α (14.1 ± 10.0 vs 23.9 ± 16.4 pg/mL, P < 0.005), interleukin (IL)-2 (0.6 ± 0.4 vs 1.2 ± 0.6 pg/mL, P < 0.0001), IL-6 (4.7 ± 6.8 vs 7.3 ± 9 pg/mL, P = 0.001), and IL-10 (7.5 ± 6.8 vs 16.8 ± 19.2 pg/mL, P < 0.01), whereas no differences were observed in serum.

Conclusion:
Results suggest that (1) inflammatory mediators play a minor role in the maintenance of chronic pain in contrast to initiation of acute pain, (2) chemokines/cytokines are downregulated in chronic pain, or (3) chemokines/cytokines have a protective role for nerve regeneration that is disturbed in patients with chronic pain.
Long-Term Orbito-Ocular Outcomes following Le Fort III and Monobloc Distraction Osteogenesis in Patients with Syndromic Craniosynostosis
Authors: Pontell Matthew E. , Wagner Connor S. , Reddy Neil , Salinero Lauren K. , Barrero Carlos E. , Swanson Jordan W. , Bartlett Scott P. , Taylor Jesse A. 
Published: February 2024

Background:
Exorbitism in patients with syndromic craniosynostosis is often managed by Le Fort III (LF3) or monobloc (MB) distraction osteogenesis (DO). This study compared short- and long-term orbital craniometrics after LF3DO/MBDO and related these findings to symptom relief.

Methods:
Patients undergoing LF3DO or MBDO from 2000 to 2021 with preoperative and postoperative imaging were included. Postoperative computed tomographic (CT) scans were categorized as early (<1 year) or late (>1 year), and age-matched control CT scans were compared with late postoperative scans. Superoinferior orbital rim position, relative globe position, and orbital volume were analyzed. Symptoms were assessed by a patient-reported outcome analysis.

Results:
Thirty-four patients (LF3DO, n = 16; MBDO, n = 18) were matched by age at surgery, sex, syndrome, and age at imaging. Time to late CT scan was 6.2 years (LF3DO) and 7.5 years (MBDO). Between early and late postoperative time points, LF3DO patients experienced no change in inferior rim position. MBDO patients experienced a decrease in inferior orbital rim position of 4.7 mm (P = 0.005), but superior orbital rim distance remained stable. Comparison of late scans and age-matched controls revealed no difference in inferior or superior orbital rim position in LF3DO patients, but the superior orbital rim distance was longer in MBDO patients (P = 0.015). Patient-reported outcome response rate was 76% with a median follow-up of 13.7 years. Most (81%) symptomatic patients improved, 19% remained symptomatic, and no patients worsened.

Conclusions:
LF3DO and MBDO achieved stable orbital craniometric changes, with improved stability at the inferior orbital rim after LF3DO. Craniometric changes were associated with long-term exorbitism symptom relief.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Cumulative Stress Across the Life Course and Biological Aging in Adulthood
Authors: Suglia Shakira F. , Clausing Elizabeth S. , Shelton Rachel C. , Conneely Karen , Prada-Ortega Diddier , DeVivo Immaculata , Factor-Litvak Pam , Cirillo Piera , Baccarelli Andrea A. , Cohn Barbara , Link Bruce G. 
Published: February 2024

ABSTRACT

Objective
Psychosocial stressors have been linked with accelerated biological aging in adults; however, few studies have examined stressors across the life course in relation to biological aging.

Methods
In 359 individuals (57% White, 34% Black) from the Child Health and Development Studies Disparities study, economic (income, education, financial strain), social (parent-child relations, caretaker responsibilities) and traumatic (death of a sibling or child, violence exposure) stressors were assessed at multiple time points (birth and ages 9, 15, and 50 years). Experiences of major discrimination were assessed at age 50. Life period stress scores were then assessed as childhood (birth–age 15 years) and adulthood (age 50 years). At age 50 years, participants provided blood samples, and DNA methylation was assessed with the EPIC BeadChip. Epigenetic age was estimated using six epigenetic clocks (Horvath, Hannum, Skin and Blood age, PhenoAge, GrimAge, Dunedin Pace of Aging). Age acceleration was determined using residuals from regressing chronologic age on each of the epigenetic age metrics. Telomere length was assessed using the quantitative polymerase chain reaction–based methods.

Results
In linear regression models adjusted for race and gender, total life stress, and childhood and adult stress independently predicted accelerated aging based on GrimAge and faster pace of aging based on the DunedinPace. Associations were attenuated after adjusting for smoking status. In sex-stratified analyses, greater childhood stress was associated with accelerated epigenetic aging among women but not men. No associations were noted with telomere length.

Conclusions
We found that cumulative stressors across the life course were associated with accelerated epigenetic age, with differences by sex (e.g., accelerated among women). Further research of this association in large and diverse samples is needed.