bluuebunny/crossref_metadata_2025 huggingface dataset:
Can Preoperative C2 Slope Predict Postoperative Cervical Sagittal Imbalance After Laminoplasty?
Authors: Ruomu Qu , Siyuan Qin , Ben Wang , Yiyuan Yang , Yanbin Zhao , Shengfa Pan , Xin Chen , Zhongjun Liu , Feifei Zhou , Liang Jiang
Published: February 2025

Study Design

Retrospective study.

Objective

To investigate the impact of preoperative C2 slope (C2S) on change in sagittal vertical axis (SVA) and postoperative cervical sagittal imbalance (CSI) after laminoplasty (LP).

Methods

Consecutive patients who underwent LP between January 2015 and January 2022 with a minimum of 12-month follow-up were reviewed. The clinical variables and radiographic measurements were assessed. Patients were divided into improvement (ΔcSVA ≤ −10 mm), stable (−10 mm ≤ ΔcSVA <10 mm), and CSI groups (ΔcSVA≥10 mm). Correlation analysis was performed to explore the associations between ΔcSVA and preoperative factors, postoperative change and outcome variables. Multivariable logistics regression was conducted to determine the factors predicting CSI.

Results

Over the 186 enrolled patients, 23 developed CSI. The CSI group presented with significantly lower preoperative cSVA, greater cervical lordosis (CL) and C2S. At the final follow-up, the CSI group presented significantly higher increase in neck pain, C2S and C7S, and greater loss in CL and range of motion at flexion position. Correlation analysis revealed that ΔcSVA is correlated positively to preoperative CL and surgical segments and negatively to preoperative C2S and cSVA. Multivariable regression revealed that lower preoperative C2S ( P = 0.026) was risk factor for postoperative CSI, with 8.9 as a potential cut-off value for C2S.

Conclusions

Lower preoperative C2S slope was risk factor for post-laminoplasty CSI. The cut-off value of C2S was 8.9. Laminoplasty should be carefully considered for patients with low C2S due to risk of postoperative CSI.
Magnitude and Associated Factors of Depression among Hypertensive Patients Attending Hospitals in Arba Minch Town, South Ethiopia
Authors: Ezo Elias , Takele Tamirat , Mezgebu Taye , Zekiwos Asnakech , Admasu Sentayehu , Ossabo Getachew , Birhanu Bethelhem , Amare Eldana , Mechal Ayalnesh
Published: February 2025

Background

The presence of depression among hypertensive patients leads to a lack of adherence to treatment and poor compliance with lifestyle adjustments.

Objectives

To assess the magnitude and associated factors of depression among hypertensive patients attending hospitals in Arba Minch town, Gamo zone, south Ethiopia, 2024.

Methods

An institution-based cross-sectional study was employed from 1 May to 30 June 2024. The total sample size was 395. A systematic random sampling technique was used. Data was collected through face-to-face interviews. Data was entered into Epi Data version 3.1 and then exported to the SPSS version 25 statistical package for analysis. Logistic regression analysis tested the association between the independent and the outcome variables. Finally, a significant independent association was interpreted at a P-value of less than 0.05 with 95%CI.

Result

The magnitude of depression among hypertensive patients was 43.6% with 95% CI (38.2–48.7). Taking multiple antihypertensive medications [AOR: 2.19, 95%CI: 1.16–4.16], history of admission [AOR: 0.24, 95%CI: 0.12–0.46], blood pressure status [AOR: 0.07, 95%CI: 0.03–0.16], body mass index <18.5 kgm2 [AOR: 0.12, 95%CI: 0.02–0.83], 18.5–24.9 kgm2 [AOR: 0.14, 95%CI: 0.04–0.52], 25–29.9 kgm2 [AOR: 0.23, 95%CI: 0.06–0.91], family history of hypertension [AOR: 3.06, 95%CI: 1.27–7.37], family history of depression [AOR: 5.01, 95%CI: 2.02–12.43], ever alcohol drinker [AOR: 3.37, 95%CI: 1.32–8.58], and ever smoke cigarette [AOR: 3.44, 95%CI: 1.26–9.34] were associated with depression among hypertensive patients.

Conclusion

The number of antihypertensive medications, history of admission, blood pressure status, body mass index, family history of hypertension, family history of depression, ever alcohol drinker, and ever smoked cigarette were significantly associated with depression among hypertensive patients. Therefore, limiting the number of medications, controlling blood pressure, reducing body mass index, screening and treating family-related hypertension and depression, and abstinence from alcohol and smoking might reduce the burden of depression among hypertensive patients.
Online Review-based Product Recommendation Using Mellivora Heron Optimization-based BiLSTM Model in E-Commerce Systems
Authors: Chowdhary Mohit , Chahal Poonam
Published: February 2025

Recently, a recommender system retrieves patterns from online reviews with the user's past interactions and provides future recommendations for users to purchase as well as consume with the upsurge development of Internet technology. By conducting sentiment analysis on a large number of user reviews on e-commerce platforms, user satisfaction can be successfully increased. However, numerous existing literature fail to extract certain implicit information and face difficulties in predicting the precise sentiment polarities of the user reviews because of the variations in sequence length, textual order, and complicated logic. To address the drawbacks of the existing techniques, the proposed research exploited the Mellivora Heron Optimization-based BiLSTM (MHO-based BiLSTM) model for product recommendation with higher quality. By incorporating the semantic ontology graph-based feature extraction involving Euclidean distance, cosine similarity, and word embeddings, along with graph embedding assists in enhancing the recommendation system. Specifically, the proposed Mellivora Heron Optimization algorithm optimally tunes the BiLSTM model to capture the context information efficiently and boosts the classifier accuracy. Moreover, a highly accurate and pertinent recommendation system for diverse scenarios is produced by combining the Spark architecture, Semantic Ontology Graph, BiLSTM classifier, and cutting-edge algorithm. With 80% of training, the MHO-based BiLSTM model for the review-based recommendation system utilizing the Amazon Product dataset obtained the accuracy, sensitivity, and specificity values of 95.29%, 95.77%, and 94.81% and outperformed other existing techniques. Similar results were found for the Amazon Video Games dataset, with values achieved during 80% of training are 96.23%, 97.20%, and 95.25%. Meanwhile, the MHO-based BiLSTM model attained the values of 96.73%, 97.71%, and 95.57%, respectively for the Amazon Video Games dataset for k-fold 10 analysis.
Developing and implementing a nurse-delivered and a web-based dyadic psychoeducational program for people with advanced cancer and their family caregivers: sharing experiences from a three-arm international randomized controlled trial (DIAdIC)
Authors: De Vleminck Aline , Van Goethem Vincent , Dierickx Sigrid , Matthys Orphé , Beernaert Kim , Gronvold Mogens , Larkin Philip , Guberti Monica , Witkamp Erica , Reid Joanne , Bristowe Katherine , Deliens Luc , Lapeire Lore ,   DIAdIC Team, Hudson Peter , Cohen Joachim
Published: February 2025

Background:

Each year millions are diagnosed with cancer, impacting both patients and caregivers. Few interventions target both patients and family caregivers together, despite their shared experiences. While dyadic psychoeducational programs are gaining attention, evidence on developing and implementing these in international trials is limited. The DIAdIC trial faced unique challenges requiring innovative solutions to maintain study integrity.

Objectives:

To present our experiences with the development and implementation of two dyadic psychoeducational home-based programs, FOCUS+ and iFOCUS in the context of a randomized controlled trial (RCT) in six European countries.

Design:

A case report detailing our experiences in the development and implementation of two dyadic psychoeducational home-based programs (one face-to-face and one web-based) across multiple countries, highlighting the challenges and mitigating strategies in an international context.

Methods:

A chronological narrative describing experiences with the development and implementation of iFOCUS and FOCUS+.

Results:

The FOCUS+ and iFOCUS programs were successfully developed for the European context through rigorous translation and adaptation processes. Despite recruitment challenges including COVID-19 restrictions and administrative hurdles, 431 patient-caregiver dyads were enrolled across 6 European countries. Quantitative and qualitative data assessed the outcomes of FOCUS+ and iFOCUS interventions, including the primary endpoints of emotional functioning and self-efficacy. Fidelity was evaluated using audio recordings, checklists, and user data. Challenges in trial management were addressed with flexible timelines and technical support.

Conclusion:

The international DIAdIC trial developed and implemented two psychoeducational dyadic programs for patients with advanced cancer and their family caregivers. Based on our experiences we share several insights for future similar studies. These relate to the attention needed for context-specific adaptations when using existing interventions or programs, the translation of human-facilitated programs to standalone eHealth versions, the challenges of adopting a dyadic focus in the study, the pragmatic challenges of conducting an RCT and evaluating implementation and effects, and the technology used for study management.
Community Perspectives on Inequalities in the Provision of Basic Healthcare Services for the Most Vulnerable Populations in the Eastern Congo: A Qualitative Study
Authors: Bwirire Dieudonné , Crutzen Rik , Letschert Rianne , Ntabe Namegabe Edmond , Cheruga Bonfils , Mukwege Juliette , Amisi Kasaya Trésor , de Vries Nanne
Published: February 2025

Background

There is a notable lack of evidence regarding the factors that shape the provision of essential healthcare services in post-conflict settings.

Purpose

This study aimed to explore and describe the factors influencing the provision of basic health care services for the most vulnerable populations in the Eastern Congo.

Method

Employing a qualitative research approach, twenty individual interviews with community members and thirteen focus group discussions were conducted. Participants were drawn from three geographically and demographically diverse locations with a history of decades-long armed conflicts in the Congo. Inductive thematic coding used the Health System Dynamics Framework categories (i.e. goals and outcomes, values and principles; service delivery; the population; the context; leadership & governance; and the organization of resources (finances; human resources; infrastructure and supplies; knowledge and information), while allowing for additional themes.

Results

Our findings are presented thematically according to these ten categories. The following factors were perceived as key areas enabling or hindering healthcare provision to the community: (1) the context for organizing basic healthcare service delivery is complex and challenging; (2) the population plays a crucial role as an active producer of health and potential change agents; (3) there is a poor strategic policy framework to guide local-level communities in the provision of basic healthcare services; (4) several critical barriers and facilitators related to effective healthcare service delivery were identified; (5) the classification of basic health service delivery methods to meet the healthcare needs of the vulnerable population; (6) the healthcare system is pluralistic and consists of multiple overlapping systems and providers; and (7) service providers and potential service users still consider access to basic healthcare services challenging, potentially resulting in reduced coverage.

Conclusion

These findings suggest that substantial changes in the factors contributing to the provision of basic healthcare services are necessary to ensure the delivery of basic healthcare services to the most vulnerable populations in the Eastern Congo. Consequently, there is a critical need to reconsider the healthcare delivery system, specifically addressing these contributing factors in the context of the Eastern Congo.
Onset and Pattern of Puberty in Apparently Healthy Sudanese Children: A Cross-Sectional Multi-Center Community-Based Study
Authors: Hemmeda Lina , Mohammed Omer A. , Elgadi Ammar , Tarig Abdalla Mohamed Malaz , Ariss Nifal S. , Abdel Majeed Mohamed Salih Omaima , Mohamed Ahmed Khabab Abbasher Hussien
Published: February 2025

Background. Puberty, a stage of development involving sexual maturation, is not well understood in Sudan regarding the onset and pattern of puberty in elementary school boys and girls. Objectives. To investigate the average ages and patterns of pubertal development of male and female school children. Methods. A one-year study involved 1584 students from 50 elementary schools. Result. The study involved 1584 students, with 58.6% male and 41.4% female. The minimum age for pubertal signs was 9 years. Boys showed increased height, body build, interest in adult behavior, acne, gynecomastia, pubic hair growth, axillary hair growth, facial hair growth, while girls showed increased height, breast buds, interest in adult behavior, and menarche. Conclusion. The study revealed that puberty typically begins at 9 years old in both males and females, with pubic hair development occurring before height increase in boys, breast budding and pubic hair appearing later in girls, particularly in Sudan.
Effects of neuromuscular electrical stimulation during hemodialysis on muscle strength, functional capacity and postural balance in patients with end-stage renal disease: a randomized controlled trial
Authors: Machfer Amal , Fekih Nadia , Ammar Achraf , Hassen Hayfa Ben Haj , Daab Wael , Amor Hassen Ibn Hadj , Bouzid Mohamed Amine , Chtourou Hamdi
Published: February 2025

Background

Hemodialysis patients (HD) have a limited physical capacity and this often means low adherence to rehabilitation programs based on conventional exercise. This study investigated the effectiveness of neuromuscular electrical stimulation (NMES) during HD therapy on muscle strength, functional capacity and postural balance in HD patients.

Methods

Twenty-two HD patients were randomly assigned to a control group (CG) or a neuromuscular electrical stimulation training group (NSTG). The NSTG underwent NMES on the quadriceps muscle during HD sessions for 12 weeks, three times per week (40 min per session. Center of pressure (COP) displacement in the mediolateral direction (COPx), in the anteroposterior direction (COPy), and the COP area (COP area) were recorded using a stabilometric platform. Timed Up and Go test (TUG) and Sit to Stand (STS30) tests, 6-minute walking test (6MWT), and the maximal voluntary contraction (MVC) were measured before and after the intervention in both groups.

Results

There was a significant increase in MVC (+ 24.5%; P < 0.01), 6MWT (+ 9.8%; P < 0.05) and STS30 (+ 25.6%; P < 0.01) performance in the NSTG following the NMES intervention period. A significant reduction was observed in TUG (-11.8%; P < 0.01), COPx(-20.1%; P < 0.05) and COPy (-24.7%; P < 0.01) following the intervention period only in the NSTG. However, no significant changes were observed in the CG following the intervention period.

Conclusion

This study supports the effectiveness of intradialytic NMES to improve muscular strength, functional capacity and postural balance in HD patients. Given the limited implementation of exercise programs in dialysis clinical practice, NMES during HD sessions offers a novel therapeutic alternative to enhance physical condition and quality of life in these patients.

Trial registration

Pan African Clinical Trial Registry Identifer: PACTR202206634181851 Registered on 21/06/2022. Registered trial name: Beneficial Effect of Intradialytic Electrical Muscle Stimulation in Hemodialysis Patients.
Evaluating the risk of comorbidity onset in elderly patients after a cancer diagnosis
Authors: Islam Md Tamzid , Saif Md Saiful Islam , Alam Naima , Pepper Sam , Ratnayake Isuru , Mudaranthakam Dinesh Pal
Published: February 2025

Background

Cancer is a critical disease that affects a person physically, mentally, socially, and in many other aspects. During the treatment stage of cancer, patients suffer from various health complexities, especially elderly people, which might result in the onset of other diseases development of a comorbid condition. Several studies have shown comorbidity plays a crucial role in cancer survival. However, there remains a lack of comprehensive statistical techniques at the national level studies to assess the significance of comorbidities development in cancer. Our research aims to address this gap by comparing cancer and non-cancer individuals over four years’ time period.

Methods

The Health Retirement Study (HRS) data was used to extract information from 6651 participants aged more than 50. Within a 4-year time span, cross-sectional observations were created whether comorbidities or not based on the development of diseases such as high blood pressure, diabetes, heart disease, stroke, lung disease, and psychological disease.

Results

In the multivariable regression model, we observed higher chances of developing comorbidity (OR = 1.321, p-value 0.0051) among the cancer group compared to the non-cancer group, adjusting the socio-economic factors. Moreover, the socio-economic factors were found to be significantly associated with cancer leading to applying the propensity score matching with (1:3 matching). Finally, the balanced data also showed significantly higher chances of developing comorbidity (OR = 1.294, p-value 0.0207) among cancer patients.

Conclusions

The above findings demonstrated the imperative development of enhanced treatment protocols, which prioritize the overall health of cancer patients, thereby reducing their susceptibility to additional illnesses.
Weight bias among students and employees in university settings: an exploratory study
Authors: Sohier Léonie , Brearty Claudia Mc , LeBlanc Stéphanie , Chartrand Dominic J. , St-Laurent Audrey , Spahis Schohraya , Philibert Léonel , Mangliar Inès Auclair , Gagnon-Girouard Marie-Pierre , Lakritz Clara , Iceta Sylvain
Published: February 2025

Background

Weight bias and stigmatization are highly prevalent in modern society, especially in educational settings, such as universities. Despite extensive documentation of the adverse consequences on students’ daily functioning and psychological health, there is limited literature regarding factors associated with weight bias and its extent in Quebec universities.

Objectives

This exploratory study aims to assess the prevalence of weight bias and experiences of weight-related stigmatization, as well as to examine their associations with gender, psychological health problems, and status (students or employees) in a college environment in the province of Quebec.

Methods

Participants were recruited via their university emails. A total of 292 students and 129 university employees participated in an online survey distributed via the secure REDCap platform. The following data was collected: sociodemographic information, status (students or employees), body weight, experiences of stigma, and prejudice towards people living with a higher weight (Fat Phobia Scale; FPS).

Results

Approximately half of the respondents reported experiencing weight-related stigma (44.7%), and half indicated holding prejudice towards overweight people (51.1%), with a moderate rate of bias according to the FPS (3.25). Experience of weight-related stigma was found to be associated with gender (X
2 = 7.88, p = 0.019), and a higher prevalence of psychological health problems (X
2 = 9.41, p = 0.002), while having prejudice was associated with gender, with men scoring higher at the FPS (F = 7.64, p = 0.006), but not with the status (student or employee). The regression model identified significant effects of status [F(4, 347) = 2.856, p = 0.005] and the interaction between gender and status [F(4, 347) = -2.326, p = 0.021] on the FPS scores.

Conclusions

Various factors are associated with the experience of weight bias and stigmatization towards people with higher weight in the college population. Campaigns to prevent and reduce weight-related bias should be aimed specifically at staff members as well as students. Future research should examine weight bias internalization as a mediator between self-perceived weight and prejudice.
Nursing graduates’ perceived future career pathway and career shift tendency in Egypt: a cross sectional study
Authors: Kotp Mohamed Hashem , Aly Mohamed Ahmed , Ismail Hossam Aly , Elmoaty Aliaa Ezz Eldin Abd , Basyouny Hasan Ahmed Awad
Published: February 2025

Purpose

Addressing the dynamics shaping nurses’ career trajectories and strategies to support workforce stability and retention in the healthcare sector. The aim of this study was to explore nursing graduates’ perceptions of their future Career pathways, and their tendency toward career shifts. Additionally, the study examined the factors influencing career shift tendencies and the relation between career pathway perceptions and career shift tendencies.

Methods

A descriptive cross-sectional study was used, with an online distributed questionnaire for study participants from different nursing graduates’ categories. That included demographic characteristics, a section that measured nursing graduates’ future career pathway perception, and career shift tendency.

Results

Nursing graduates in Egypt were having a positive perception regarding their future career pathway. However, more than one quarter of them were considering career shift represents potential workforce instability and dissatisfaction within the nursing profession and financial factors was one of the main provoking drivers for career shift tendency. In addition, nursing graduates’ perception of career pathway had a significant effect on their career shift tendency in future.

Conclusion

Based on the findings of this study, further efforts should be made to confront nursing shortage in Egypt, implementing targeted interventions to support nursing graduates in navigating their career pathways. Additionally, proactive measures should be taken to address the identified factors driving intentions to leave the profession, such as improving workplace conditions, fostering intergenerational collaboration, and offering mentorship programs. These strategies are essential for fostering a resilient and satisfied nursing workforce and ensuring the delivery of high-quality patient care in the healthcare sector.
An outbreak of Ralstonia insidiosa in hospitalized children
Authors: Copana-Olmos Raul , Calderon-Lopez Maria Elena , Ledezma-Hurtado Wara , Ramos-Cardenas Roxana , Calle-Cruz Hirma , Cano-Guzman Fatima
Published: February 2025

Introduction

Healthcare-associated infections (HAIs) pose significant public health challenges, increasing patient morbidity, mortality, and healthcare costs. This study analyzes an outbreak of Ralstonia insidiosa in children admitted to a pediatric referral hospital, focusing on implemented control and prevention measures.

Methods

A prospective observational study was conducted during the outbreak, emphasizing control measures in a pediatric hospital.

Results

Eighteen cases were reported over 19 epidemiological weeks, with an attack rate of 8.79% in pediatric intensive care units (PICU) patients and 1.76% of those in other wards. The affected children were primarily those hospitalized for over 14 days, with invasive devices, admitted to PICU, and having underlying conditions. Symptoms included vomiting, fever, and cough. Outbreak control was achieved through epidemiological and antimicrobial surveillance measures.

Conclusions

Ralstonia insidiosa is an emerging nosocomial pathogen associated with risk factors such as invasive devices and prolonged PICU stays. Effective control measures, leveraging available resources, can mitigate outbreaks.
Postoperative endophthalmitis treatment with antibiotics associated or not with pars plana vitrectomy: a randomized clinical trial
Authors: Bergamo Vinicius Campos , Nakayama Luis Filipe , de Moraes Nilva Simeren Bueno , Tavares Ivan Maynart , De Queiroz Campos Mauro Silveira , Hofling-Lima Ana Luisa , Maia Maurício
Published: February 2025

Background

Postoperative endophthalmitis (PSE) is a severe ocular complication that can lead to irreversible vision loss or even globe atrophy. The Endophthalmitis Vitrectomy Study (EVS) historically guided PSE management but is increasingly questioned due to advances in pars plana vitrectomy (PPV) techniques and its narrow focus on cataract surgery. This study aimed to compare PPV followed by intravitreal antibiotic injection at the end of surgery (PPV + IVAIES) with intravitreal antibiotic injection alone (IVAI) in managing PSE.

Methods

This randomized clinical trial included 35 pseudophakic patients with PSE following cataract extraction, anti-vascular endothelial growth factor (anti-VEGF) injections, or glaucoma surgeries. Participants were randomized to receive either PPV + IVAIES (n = 12) or IVAI (n = 23). Best-corrected visual acuity (BCVA) was assessed at baseline and days 7, 30, 60, and 90 post-intervention. Clinical worsening, defined as lack of improvement or progression of symptoms within 48–72 h, guided retreatment protocols. Group A (PPV + IVAIES) received repeat IVAI if required, while Group B (IVAI) underwent delayed PPV with repeat IVAI. Statistical significance was assessed using repeated measures ANOVA and logistic regression.

Results

Both groups showed significant BCVA improvement (p < 0.001). PPV + IVAIES resulted in faster recovery, with superior BCVA at day 7 (p = 0.019) and day 30 (p = 0.041). Retreatment was required in 39.1% of the IVAI group but not in the PPV + IVAIES group (p = 0.015). Subgroup analysis indicated a trend toward better early outcomes with early PPV (p = 0.029).

Conclusions

Early PPV + IVAIES provides faster visual recovery and reduces retreatment rates compared to IVAI alone. Multicenter studies are warranted to confirm these findings and refine clinical guidelines.

Trial registration ClinicalTrials.gov identifier: NCT04192994.
Outbreak of circulating vaccine-derived poliovirus type 2 (cVDPV2) in Indonesia in 2023–2024
Authors: Ashique Sumel , Srivastava Shriyansh , Sridhar Sathvik Belagodu , Kumar Sachin , Rahaman Abdul S. K. , Hussain Md Sadique , Mohanty Aroop , Sah Sanjit , Mehta Rachana
Published: February 2025

Graphical Abstract
Use of dornase alfa in the management of life-threatening mucostasis in airway stents: its efficacy and safety
Authors: Turan Demet , Chousein Efsun Gonca Ugur , Cortuk Mustafa , Elkhatroushi Burcu Babaoğlu , Ozgul Mehmet Akif , Cetinkaya Erdogan
Published: February 2025

Purpose

Airway stents (AS) are a last-resort treatment for central airway obstructions when airway patency cannot be maintained above 50%, in patients unsuitable for surgery, or with recurrence after surgery. However, AS placement can cause complications, including life-threatening mucostasis, which is challenging to manage. Standard methods to prevent mucus retention often have limited efficacy. Dornase alfa, a mucolytic agent widely used in cystic fibrosis (CF) patients, has shown efficacy in secretion control in mechanically ventilated pediatric non-CF patients. This study evaluates the efficacy and safety of nebulized dornase alfa in managing AS-related life-threatening mucostasis.

Results

Fourteen patients (mean age 56.3 ± 15.6 years) with life-threatening mucostasis were identified among 255 stented patients (2017–2019). Eight had Y-shaped stents, and 6 had non-Y-shaped stents (5 hourglass and 1 OKI); 13 stents were placed for benign conditions and 1 for malignancy. Mucus grades (defined by Marchese et al.) and the number of bronchoscopies needed 6 months before and after dornase alfa were evaluated. Statistically significant decreases were observed in both mucus grades (2.36 ± 0.49 to 0.79 ± 0.59, p < 0.001) and the number of bronchoscopies per patient (3.21 ± 0.89 to 2.00 ± 1.04, p = 0.002). The shape of AS and the presence of bronchiectasis on thoracic computed tomography scans had no significant impact on mucostasis development. No side effects related to dornase alfa were observed.

Conclusion

Dornase alfa significantly reduced mucus burden and bronchoscopic interventions in AS-related life-threatening mucostasis, demonstrating its safety and efficacy for managing this complication.
NGS-based molecular panel analysis of metastatic prostate cancer for daily routine: How often do we detect druggable mutations?
Authors: Steenbock Olivia , Rieger Constantin , Heidenreich Julian , Paffenholz Pia , Pfister David , Weiten Richard , von Brandenstein Melanie , Heidenreich Axel
Published: February 2025

203

Background:
Guidelines recommend molecular analysis to identify druggable mutations after failure of the first-line systemic therapy for metastatic prostate cancer (mPCA). We report our results of molecular diagnostics in mCRPC patients.
Methods:
From 2018 to 2023, 311 mCRPC patients underwent molecular panel analysis of archived prostatectomy samples (n=96) or CT-guided biopsies of progressive metastases (n=215) using standardized NGS procedures after the failure of first- or second-line systemic therapy. Mutation analysis was initially performed using NGS with a custom "Prostate Cancer Panel" of 18 multiplex PCR amplicons (AR, ATM, AURKA/MYC, BRCA1/2, CDK12, CTNNB1, DLL3, ETS family, FOXA1, FOXO1, MED12, PIK3CA, PTEN, RAD51C, TP53, Wnt-Pathway), generated using a GeneRead DNAseq Custom Panel V2 (Qiagen). Since 2023, we perform apply the TSO500 panel in selected cases. Analysis of HRD was performed by combining BRCA1 and BRCA2 mutations with the HRD score (Genomic ScarScore GSS) using the HANDLE HRD Focus Panel (Halo-shape Annealing and Defer-Ligation Enrichment, AmoyDx). The data were evaluated using the following thresholds: tumor cell content ≥ 30%, GScore positive at ≥ 50, HRD positive: GScore at ≥ 50 or BRCA1/2 category 4/5 mutation. In addition MSI-high and mutations of MSH2, MSH6, PMS2, and MLH1 were analysed. The following databases were reviewed to identify druggable mutations: OncoKB, ClinVar, JAX-CKB, COSMIC, and My Cancer Genome.
Results:
Out of 311 biopsies, 299 (96%) had sufficient DNA content for NGS. NGS was performed from prostate (31%), lymph node (30%), visceral (15%), and bone (24%) metastases with informative DNA retrival in 95%, 95%, 92%, and 85%, respectively. Overall, 157 patients (50.5%) had no or non druggable mutations, while 154 patients (49.5%) exhibited druggable mutations. HRD gene mutations (BRCA1/2, ATM, CDK12, CHEK2, FANCA, Rad51C) and inactivating p53 mutations were observed in 66 patients (22%). 3 patients had p53 mutations with gain-of-function resulting in ATM inactivation. 50% HRD gene mutations including a positive HRD score were pathogen and treated with PARPi resulting in a progression-free survival of 3-28 months. Activating androgen receptor mutations and inactivating PTEN/activating PIK3Ca mutations were found in 42 (14%) and 24 (8%) patients, resp. Switch of treatment for AR mutation resulted in PFS of 6-9 months. Mismatch repair deficiency/MSI high mutations were identified in 3 cases who received pembrolizumab with a PFS of 4-8 months.
Conclusions:
NGS analysis in mCRPC reveals mutations in two-thirds of patients, of which 41% are already druggable. Only 50% of druggable mutations are based on BRCA1/2 or ATM. NGS analysis should be integrated into the diagnostic armamentarium following failure of first-line systemic therapy for mCRPC.
Patient characteristics and survival in primary prostate sarcomas: An analysis of the SEER database.
Authors: Kaushish Ayush , Lee Hyun , Han Joseph , Baralo Bohdan , Paul Asit KR
Published: February 2025

271

Background:
Primary prostate sarcoma (PPS) is a rare neoplasm of prostate and is associated with poor survival outcome.
Methods:
We conducted an analysis of patients with PPS in the Surveillance, Epidemiology, End Results (SEER) database from year 2000 to 2020. Patients were identified by using the primary cancer site codes for prostate as well as histological codes (ICD-O-3) that matches the list of sarcoma histology found in the NCCN soft tissue sarcoma and bone cancer guidelines. Data for demographics, disease extent and median overall survival (OS) were obtained. Sarcomas mixed with carcinomas, so-called carcinosarcomas, were included in the analysis. OS data of prostate adenocarcinoma from same database were obtained for a comparison.
Results:
During the period analyzed, a total of 1,120,527 patients with primary prostate neoplasms were identified. Among them, 239 patients (0.0002%) had PPS. Majority were Caucasian (67.8%) followed by Hispanics (13.4%) and African Americans (8.8%). The most common histology was rhabdomyosarcoma (28.5%), followed by leiomyosarcoma (21.8%), carcinosarcoma (16.7%), and unspecified sarcomas (8.8%).Among 221 patients with known extent of disease, 29.4%, 37.1% and 33.5% had localized, locoregional and distant metastatic disease, respectively. Overall, PPS was associated with worse OS than prostate adenocarcinoma (28 months vs. 183 months, P<0.01). OS for patients with localized, regional, and distant diseases were 54, 39, and 18 months, respectively (P=0.04). Patients with carcinosarcomas had worse OS than those with pure sarcomas (15 months vs. 34 months, P<0.001). Among patients with locoregional disease, 19 (14.2%) received chemotherapy only, 84 (62.7%) received surgery only, and 31 (23.1%) received both chemotherapy and surgery. Median OS was not reached in those with locoregional disease who did not receive surgery while it was 44 months in those who received surgery (P=0.055). As for those with distant metastasis, 37 (56.1%) received chemotherapy only, 13 (19.7%) received surgery only, and 16 (24.2%) received both chemotherapy and surgery. Median OS for those with metastatic disease who received chemotherapy versus no chemotherapy was 9 months versus 19 months (P=0.063).
Conclusions:
PPS was rare and associated with worse survival outcome compared with prostate adenocarcinomas. Carcinosarcomas were less common than pure sarcomas and were associated with worse survival than pure sarcomas.
Evaluation of circulating kidney injury marker-1 (KIM-1) as a prognostic and predictive biomarker in advanced renal cell carcinoma (aRCC): Post-hoc analysis of CheckMate 214.
Authors: Xu Wenxin , Vemula Sai Vikram , Motzer Robert J. , Chhibber Aparna , Chowbene Deepthi , Perrot Nahuel , Liu Xiaowen , Bonventre Joseph , Choueiri Toni K. , McDermott David F. , Gupta Saurabh , Bhatt Rupal Satish
Published: February 2025

437

Background:
CheckMate 214 established nivolumab and ipilimumab (NIVO+IPI) as a first line standard of care regimen with superior survival and durable response versus sunitinib (SUN) in advanced RCC. Previous studies have shown that high levels of circulating KIM-1 are associated with worse prognosis and reduction in KIM-1 levels is associated with benefit from adjuvant immunotherapy. In this post-hoc analysis we evaluated whether KIM-1 levels at baseline and after 1 cycle of NIVO+IPI or SUN are associated with treatment outcomes in CheckMate 214.
Methods:
Patients with advanced RCC were randomized to NIVO+IPI or SUN as previously described. Serum KIM-1 was measured at baseline and 3 wks after first treatment dose using an enzyme based electrochemiluminescence assay. The association between KIM-1 levels and clinical outcomes was evaluated using Kaplan-Meier and Cox proportional hazards analyses.
Results:
We analyzed serum from 821 patients (75% of the CM 214 ITT population). Median KIM-1 at baseline was 660.4 pg/mL. Across both arms, higher KIM-1 levels were associated with shorter overall survival (OS) independent of IMDC risk group, nephrectomy status, and tumor burden. Benefit for NIVO+IPI versus SUN was seen across KIM-1 tertiles. Decrease in KIM-1 from baseline to C2D1 was strongly associated with progression free survival (PFS) and OS among patients treated with NIVO+IPI (Median PFS 70.8 months vs 4.2 months for patients with >30% decrease vs >30% increase in KIM-1, with median OS 85.4 vs 26.6 months, overall response rate (ORR) 69.3 % vs 13.9%), but not in patients treated with SUN.
Conclusions:
In CheckMate 214, increased levels of baseline circulating KIM-1 were associated with worse clinical outcomes both in NIVO+IPI and SUN arms. The extent of reduction in serum KIM-1 just 3 wks after single cycle of NIVO+IPI was associated with long term efficacy of this IO doublet. Circulating KIM-1 may be a useful minimally invasive biomarker for monitoring patients on RCC immunotherapy.

KIM-1 change at 3 weeks (prior to second dose of NIVO+IPI) and association with outcomes (NIVO+IPI arm).

3 week KIM-1 change
N (%)
ORR, % (95% CI)
mPFS, months (95% CI)
mOS, months (95% CI)

>30% Decrease
140 (31.7)
69.29 (60.94-76.80)
70.80 (17.84- NA)
85.36 (63.08- NA)

>10-30% Decrease
87 (19.7)
36.78 (26.69-47.80)
11.43 (6.28-18.20)
66.14 (40.44-80.10)

<10% Change
86 (19.5)
30.23 (20.79-41.08)
15.41 (10.32-20.73)
52.70 (30.26-70.67)

>10-30% Increase
56 (12.7)
23.21 (12.98-36.42)
7.13 (4.17-16.79)
40.34 (23.82-58.41)

>30% Increase
72 (16.3)
13.89 (6.87-24.06)
4.17 (3.02-8.08)
26.61 (18.79-38.44)
Lenvatinib plus tislelizumab as first-line therapy for advanced fumarate hydratase-deficient renal cell carcinoma: A single-center, single-arm, phase II study.
Authors: Kong Wen , Wu Guangyu , Xu Yunze , Wang Zaoyu , Zhang Jin
Published: February 2025

443

Background:
Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is a rare and aggressive subtype of RCC with dismal prognosis. Although bevacizumab plus erlotinib (Beva/Erlo) showed promising anti-tumor activity, treatment option was limited. Date from our retrospective study showed comparable response rates between tyrosine kinase inhibitors plus immune checkpoint inhibitors (TKI/ICI) and Beva/Erlo, while the TKI/ICI group had better overall survival. Here, we reported the preliminary result of an investigator-initiated phase II study evaluating lenvatinib plus tislelizumab for advanced FH-RCC in the first-line setting.
Methods:
Eligible patients were aged 18-80 years old, diagnosed with pathologically confirmed, unresectable advanced or metastatic FH-RCC, had measurable disease defined by RECIST 1.1 and no history of systemic therapy. A definitive diagnosis of FH-RCC was confirmed when germline or somatic FH mutations were detected via DNA sequencing. All eligible patients received concurrent therapy with lenvatinib 20 mg P.O. daily and tislelizumab 200 mg intravenously every 3 weeks until disease progression, intolerable toxicity, or withdrawal of consent. The primary end point was objective response rate (ORR). Secondary end points included disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), 1-year and 2-year overall survival (OS) rate, and safety.
Results:
From September 2023 to October 2024, 17 patients were enrolled (male: 14, female: 3). The median age was 37 (24-61). FH germline alteration was identified in 12 patients, while the remaining 5 patients were considered carrying somatic biallelic FH mutations. Thirteen patients had a history of nephrectomy. The most common site of recurrence or metastasis was retroperitoneal space (14/17, 82.1%), followed by bone metastasis (9/17, 52.9%). The median follow up was 7.0 (1.0-12.0) months. Fifteen patients were available for efficacy assessment at data cutoff，fourteen of them had an objective response (ORR 93.3%), and the complete response rate was 20.0% (3/15). The median time to response was 6 weeks. One PFS and OS event occurred. Median PFS and OS were not reached, while 6-month PFS and OS rate were 93.3% and 100% respectively. All grades and ≥G3 AE occurred in 16 (94.1%) and 4 patients (23.5%) respectively. Treatment discontinuation or dosage reduction occurred 8 patients (47.1%).
Conclusions:
Lenvatinib plus tislelizumab combination showed encouraging anti-tumor efficacy and acceptable toxicity profile. The potential of TKI/ICI/ combination to be recommended as the first-line therapy in advanced FH-RCC patient needs further evaluation. Clinical trial information:
NCT05877820
.
Site-specific disease progression in patients with metastatic renal cell carcinoma treated with first-line nivolumab plus ipilimumab or axitinib-based immunotargeted combinations.
Authors: Tsimafeyeu Ilya , Guliyev Fuad , Musayeva Gunel , Abdrakhmanov Ramil , Chubenko Viacheslav , Baklanova Olga , Zukov Ruslan , Petkau Vladislav , Myslevtsev Igor , Kahharov Alisher , Ongarbayev Bakytzhan , Kaidarova Dilyara
Published: February 2025

478

Background:
Data on site-specific progression patterns in metastatic renal cell carcinoma (mRCC) treated with immuno-oncology agents are limited. This study aimed to characterize sites of progression in patients receiving nivolumab plus ipilimumab (Nivo-Ipi) or axitinib-based immunotargeted combinations in the first-line setting.
Methods:
A retrospective, observational cohort study included patients with clear-cell mRCC who received either Nivo-Ipi (Cohort A) or pembrolizumab-axitinib and avelumab-axitinib (Cohort B) from 2018 to 2024. The primary objective was to assess the occurrence of new lesions in different organs. Secondary analysis evaluated disease progression by an increase of more than 20% in target lesion size.
Results:
A total of 334 patients were identified, with radiographic progression observed in 86.3% (107/124) of Cohort A and 60% (126/210) of Cohort B. In the ITT population (n=233), the median age at mRCC diagnosis was 59.7 years (range 31–84), 79% were male, 74% had undergone nephrectomy, 61% had intermediate IMDC risk, and 64% had two or more metastatic sites. Cohort B had a younger median age (60.2 vs. 65.4 years), a higher incidence of bone metastases (28.6% vs. 13.1%), and more favorable risk (15.1% vs. 0.9%) compared to Cohort A. The site-specific rate of new lesions differed between cohorts (Table). Progression due to increased target lesions occurred in 60.7% (65/107) of Cohort A and 77.8% (98/126) of Cohort B patients.
Conclusions:
New lesion development was more frequent with Nivo-Ipi, with lymph nodes being the most common site of new lesions of mRCC across both cohorts.

Cohort An=107
Cohort Bn=126

Baseline

At the time of progression

Baseline

At the time of progression

Patients with new lesions, n (%)
-

42 (39.3)

-

28 (22.2)

Sites of metastases, n (%)

Lung
73 (68)
81 (76)
76 (60)
79 (63)

Lymph node
55 (51)
94 (88)
68 (54)
81 (64)

Liver
27 (25)
28 (26)
39 (31)
47 (37)

Bone
14 (13)
26 (24)
36 (29)
41 (33)

Adrenal gland
19 (18)
20 (19)
20 (16)
28 (22)

Contralateral kidney
5 (5)
5 (5)
1 (0.8)
2 (1.6)

Brain
1 (1)
2 (2)
4 (3)
4 (3)

Soft tissues
4 (4)
4 (4)
1 (0.8)
1 (0.8)

Pancreas
2 (2)
3 (3)
0 (0)
2 (1.6)

Other*
5 (5)
7 (7)
9 (7)
9 (7)

*Thyroid gland, pleura, peritoneum, ovary, breast.
Current impact of ureteral carcinoma amongst racial minorities: Analysis of the National Cancer Database.
Authors: Edwards Christopher , Leelani Navid , Vazquez Rivera Katiana , West Michael , Shpeen Benjamin , Schulman Ariel
Published: February 2025

675

Background:
Upper tract cancer is a relatively uncommon type of genitourinary cancer. Lower socioeconomic status and racial disparities have long been associated with worse cancer related outcomes for various types of cancer. Our objective was to determine if racial minorities in the United States were more likely to present with ureteral cancer of stage II or greater.
Methods:
The National Cancer Database (NCDB) Hospital Comparison Benchmark Reports (HCBR) for ureter cancer from 2013 to 2022 were reviewed. Demographic and clinical data was compared between various races and ethnicities affected to determine any significant differences related to age, stage, insurance status, distance traveled, and education at presentation. Patients were stratified into two groups of patients with stage II or greater and those with less than stage II ureteral cancer. Fischer’s exact test was used to compare the proportion of Caucasian patients with stage II or greater ureteral cancer against patients of other ethnicities. Statistical significance was defined as p<0.05.
Results:
Within the NCDB HCBR database, there were 26,153 patients with ureter carcinoma spanning 1,238 hospitals, with males comprising 16, 435 (62.8%) and females 9,718 (37.2%). Caucasian patients included most cases at 22,314 (86%), followed by African American patients 1,072 (4.17%), Hispanic patients 1,047 (4.08%), Asian and Pacific Islander patients 871 (3.39%), and Native American patients 73 (0.28%). Overall stage distribution included—0: 9,342 (36.38%); I: 3,711 (14.45%); II: 2,443 (9.51%); III: 2,724 (10.61%); IV: 3,636 (14.16%). A higher proportion of Asian and Pacific Islander patients were more likely to present with Stage II or greater ureteral cancer compared to Caucasian patients (43% vs 33.9%, p<0.001). Furthermore, Asian and Pacific Islander patients were more likely to present with invasive disease (73.6% vs 63.9%, p<0.001). A higher proportion of Asian and Pacific Islander patients were found to be uninsured or have Medicaid, be from a less educated household, and were less likely to travel longer distances for care when compared to Caucasian patients (all p<0.001). Regarding presenting at stage II or greater, there was no significant difference found when comparing Caucasian patients versus African American, Hispanic, or Native American patients.
Conclusions:
Asian and Pacific Islander patients were more likely to present with stage II or greater ureteral cancer compared to their Caucasian counterparts. Future directions exploring the factors affecting these at-risk groups is vital to properly redirecting resources and improving disparities.