bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term survival of patients with lung cancer with kinase fusions (KF) treated at a tertiary community-based cancer program.
Authors: Doctor Vicki , Tan Bradford A. , Schink Julian C. , Prabhakar Dhivya , Khan Ajaz M. , Pisick Evan P. , Szymulanska-Ramamurthy Karina , Markman Maurie 
Published: June 2024

e23279 Background: Comprehensive Genomic Profiling (CGP) has been routinely obtained on patients with advanced cancers without standard-of-care therapeutic options managed in our community-based cancer program for more than a decade. Methods: In 2018, we reported that 1% (77 of 7,260 pts) who underwent CGP (Foundation Medicine Inc. hybrid capture based CGP platform) were found to have a KF abnormality (median age 53), including 55 patients (pts) (71%) with non-small cell lung cancer (NSCLC) and 22 (29%) with other malignancies. The incidence of KF in the NSCLC population tested was approximately 5%. Of the 55 patients with NSCLC, 36 pts (65%) had ALK fusions, 12 pts (22%) has RET fusions, 7 pts (13%) had ROS1 fusions. Results: This report describes long-term survival of NSCLC pts with metastatic disease within this population treated with KF targeted therapy for > 5 years. Five pts (9% of NSCLC with a KF; all females; median age 63 [range 57-72]) remain on active therapy a median of 10 years (range 6.5-12 years) from the initiation of therapy. 2 pts have EML4-ALK fusions, 1 pt has EZR-ROS1 fusion, 1 pt has CD74-ROS1 fusion, and 1 pt has ALK PRKAR1A fusion. 2 of 5 pts have continued their initial KF agent while 2 switched >1 times to an alternative KF targeted drug and 1 is currently receiving chemotherapy. Only two pts had the identical KF abnormality. Conclusions: In this series approximately 10% of NSCLC pts with a KF experienced extended survival (greater than five years) despite the presence of metastatic disease, including three patients with brain mets. It is critical to conduct molecular testing on all NSCLC pts for the presence of a kinase fusion abnormality. Treatment directed at this molecular target can result in long-term survival.
Retroperitoneal leiomyosarcoma; Demographics, clinicopathological, survival analysis, role of adjuvant radiation and genomic analysis.
Authors: Ullah Hafeez , Khan Yasinzai Abdul Qahar , Tareen Bisma , Daino Naema , Ullah Asad , Heneidi Saleh , Rasool Basil , Karki Nabin R. 
Published: June 2024

e23327 Background: Retroperitoneal leiomyosarcoma (RPL) is an exceedingly rare malignancy and is the second most common subtype of leiomyosarcomas. Most of the information concerning this rare disease is limited to case studies and few literature studies. The study's objectives were to assess the demographics, pathological factors, survival outcomes, genomic landscape and potential for targeted therapy. Methods: Data of retroperitoneal leiomyosarcoma were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, with cases diagnosed between 2000 and 2020 used for this study and the Cancer Genome Atlas containing sequencing information for 27 cases of RPL. Results: A total of 1406 cases were extracted with mean age of diagnosis of 62.1 years. Of these, RPL had a higher incidence in women (71.5%), more cases affected Whites (58.7%). Histologically, in patients with known grading, most patients’ i.e. 62.35% were grade 3, G3 (poorly differentiated). Nearly all (99.9%) patients presented with a tumor size ≥4.1 cm. Local lymph nodes metastasis were positive in 76.0% of cases when lymph node status was reported. In known cases of distant metastases, the most common site was liver (8.9%). The main treatment modality was surgery only (26.7%, hazard ratio, HR 1.17, p-value < 0.001), followed by the standard of care (surgery and radiation) (18.4%, HR 1.03, p-value < 0.001), and radiation only (18.4%). Five-year overall survival was 40% and 5-year cause-specific survival was 64%. The highest 5-year survival was observed in patients undergoing surgery and radiation (57%), and in combination therapy (chemotherapy, surgery, and radiation) the 5-year survival was 39%. Genetic analysis found the most common mutations included TP53 (51.9%), RB1 (25.9%), and ATRX (14.8%). When accounting for deep deletions and rearrangements, total frequency of the alterations was higher such that TP53 (63.0%), RB1 (51.9%), and ATRX (18.5%). Potentially actionable alterations were rare but included activating alterations in FGFR1, PIK3CA and ESR1, as well as deep deletions of BRCA1. Conclusions: Retroperitoneal leiomyosarcoma is a very rare tumor where surgery and radiation has been the conventional therapy. Our study indicates there are genetic alterations in the majority of retroperitoneal leiomyosarcoma. To further understand the pathogenesis and survival factors, patients with RPL should be enrolled into national and international registries.
Evaluation of tumor immune microenvironment for PD-L1 score and tumor infiltrating lymphocytes in high grade osteosarcomas and their correlation with disease progression.
Authors: Khan Shah Alam , PUSHPAM DEEPAM , Mridha Asit R. , Barwad Adarsh , Sampath kumar Venkatesan , Bakhshi Sameer 
Published: June 2024

e23510 Background: Tumor Immune Micro-environment is being increasingly recognised as a potential target for improving overall survival for osteosarcomas, especially in the metastatic setting. Our study purpose was to evaluate the PD- L1 (Programmed cell Death- Ligand 1) expression in neoplastic cells well as Tumor Infiltrating Lymphocyte (TIL) density of osteosarcoma specimens and correlate it with oncological outcomes. Materials & Methods: A prospective cohort study was conducted between March 2017 and March 2022 among osteosarcoma patients who underwent primary biopsy and neo-adjuvant chemotherapy followed by surgical excision at our centre. We excluded patients who had alternative diagnoses such as low grade osteosarcoma, secondary osteosarcoma, recurrent osteosarcoma as well as patients who had undergone initial treatment (chemotherapy/ surgery) outside our institute. De-paraffinized sections (4μ) incubated with primary antibody (PDL1) and a universal secondary detection kit used. Average percentage of positive cells calculated from at least 10 representative fields at 400X magnification. Positive staining was considered when ≥1% cells showed positivity. IHC scoring of PD-L1 was graded as negative, low positive and high positive. We calculated the number of TILs under 400X magnification in ten fields and then took their average. TILs staining was scored semi quantitatively using a 3 tiered scale. Results: Forty patients who fulfilled the inclusion & exclusion criteria were included in the study with most common age group being 10 to 19 years (27 patient, 68%). The male: female ratio was 1.6: 1 and the most common location of tumor was distal femur. Majority of patients had the histological subtype of conventional osteosarcoma (37 patients, 92.5%). Lung metastasis was present at time of initial diagnosis in 27 patients (67.5%). At the end of 2 years, 27 patients were alive (60%) while 13 patients had died due to disease. PD-L1 expression was negative in 17.5%, low positive in 15% and high positive in 67.5%. Among TIL category, 19 patients belonged to category 1, 10 belonged to category 2 & 11 belonged to category 3. There was significant correlation between PD-L1 expression score & TIL category. PD-L1 score did not correlate with percentage of necrosis following chemotherapy, metastasis on presentation or overall survival. Conclusions: PD-L1 score had significant correlation with density of Tumor Infiltrating lymphocytes (TIL). However, PD-L1 score did not correlate with overall survival, tumor-free survival, progression of metastasis or local recurrence.
Analysis of demographic and socioeconomic factors in mixed type rhabdomyosarcoma using NCDB.
Authors: Gill Sukhmani Kaur , Moroz Mark , Grover Jasika , Rafie Susan , Silberstein Peter T. , Heise Craig , Hsia Beau 
Published: June 2024

e23538 Background: Mixed type rhabdomyosarcoma is a rare soft tissue tumor characterized by the presence of two histologically different subtypes of rhabdomyosarcoma, commonly found in the testis. Despite a majority of the patients undergoing aggressive treatment, the prognosis is poor. Analysis of its diagnostic trends could prove valuable in understanding mixed type rhabdomyosarcoma’s epidemiology. The 2004-2020 National Cancer Database (NCDB) was analyzed to determine the demographic factors of patients with mixed type rhabdomyosarcoma. Methods: A retrospective cohort analysis of the 2004–2020 NCDB, using ICD-O-3 code 8902/3, included patients diagnosed with mixed type rhabdomyosarcoma (N = 94). Descriptive statistics were used to analyze various demographic factors such as sex, age, race, Hispanic status, educational background, insurance status, facility type and location, distance from facility, and Charlson-Deyo score. Incidence trends were examined through regression analysis. Results: The NCDB identified a total of 94 patients with a confirmed diagnosis of mixed type rhabdomyosarcoma from 2004-2020, with a slight decline in incidences diagnosed per year (R² = 0.0903). Females had a slightly higher likelihood of being diagnosed (55%) compared to males (45%), with average age at diagnosis being 40.06 years (SD = 2.8, Range = 1-90). The majority of patients were White (72%) and of non-Hispanic descent (82%). The top primary site was the testis (23%), with endometrium being another major site (15%). Most (83%) patients had a Charles/Deyo comorbidity score of 0. All patients received immunotherapy as primary treatment. Most (46%) patients were privately insured. A majority (26%) of patients received treatment at an academic/research program. A greater number (53%) of patients resided in metropolitan counties with a population larger than 1 million. Most (40%) patients belonged to the highest quartile of income earners of $74,063 or greater. Conclusions: Our research on mixed type rhabdomyosarcoma, the first NCDB analysis of its kind, aims to address a notable knowledge gap on the topic. Similar to information presented in earlier studies, our analysis revealed mixed type rhabdomyosarcoma has a relatively poor prognosis and is mostly observed in White, Non-Hispanic individuals. Analysis on the demographics of this patient population revealed most patients were top quartile income earners, resided in a metropolitan location, and were more likely to be treated at an academic/research program. Further research should aim to better understand the impact of such demographic and socioeconomic features on the diagnosis, treatment plans, and overall mortality rates of patients with mixed type rhabdomyosarcoma.
Quality of life outcomes in patients with resectable dedifferentiated liposarcoma treated with neoadjuvant immunotherapy.
Authors: Malik Neha , Peterson Susan K. , Keung Emily Zhi-Yun , Hunt Kelly , Torres Keila E , Lyu Heather , Lillemoe Heather A. , Nassif Haddad Elise F , Somaiah Neeta , Roland Christina Lynn , Scally Christopher 
Published: June 2024

e23552 Background: Currently there is a lack of robust data on health-related quality of life outcomes for patients with retroperitoneal sarcoma. The purpose of this study was to look at trends in health-related quality of life outcomes for patients and determine what symptoms impacted patients the most. Patients with surgically resectable dedifferentiated liposarcoma who were participating in a randomized, phase II, non-comparative trial of combination nivolumab (nivo) and ipilimumab (ipi/nivo) were selected to participate in this study. Methods: Five patients were randomized to participate in structured qualitative interviews. Three patients were randomized to the nivo/ipi arm and 2 to the nivo arm. The interviews were conducted at 6 separate time points, both during receipt of neoadjuvant therapy and after tumor resection. Questions were structured around ten themes which included treatment side effects, abdominal complications, appetite, energy levels, quality of life effects, and financial complications. Patient responses were transcribed, coded, and themes in symptoms during treatment were identified. Results: Different themes in symptoms emerged during each time-period of treatment. During the pretreatment period patients were more likely to report abdominal complaints that they attributed to their primary tumor. During neoadjuvant immunotherapy (week 3) patients reported more skin complaints, including the development of rashes and pruritis. These tended to improve by their preoperative visit. Patients reported typical postoperative symptoms at their 6-week post operative visit including increases in pain medications, muscle pain, and some abdominal soreness. By one year patients reported no significant symptoms and demonstrated resolution of all prior symptoms. Overall patients reported few energy and sleep related symptoms throughout their treatment course. Conclusions: For patients with resectable dedifferentiated liposarcoma receiving immune checkpoint blockade, health-related quality of life symptoms were present throughout their treatment course. Common themes that emerged demonstrated a lack of severe symptoms experienced by patients in either arm and resolution of symptoms by one year post treatment. Our interview results can help clinicians focus on symptoms that are impactful to patients in future clinical trials.
A Systematic Review Supporting the Endocrine Society Clinical Practice Guidelines on Vitamin D
Authors: Shah Vishal Paresh , Nayfeh Tarek , Alsawaf Yahya , Saadi Samer , Farah Magdoleen , Zhu Ye , Firwana Mohammed , Seisa Mohamed , Wang Zhen , Scragg Robert , Kiely Mairead E , Lips Paul , Mitchell Deborah M , Demay Marie B , Pittas Anastassios G , Murad Mohammad Hassan 
Published: June 2024

Abstract

Context
Low vitamin D status is common and is associated with various common medical conditions.

Objective
To support the development of the Endocrine Society's Clinical Practice Guideline on Vitamin D for the Prevention of Disease.

Methods
We searched multiple databases for studies that addressed 14 clinical questions prioritized by the guideline panel. Of the 14 questions, 10 clinical questions assessed the effect of vitamin D vs no vitamin D in the general population throughout the lifespan, during pregnancy, and in adults with prediabetes; 1 question assessed dosing; and 3 questions addressed screening with serum 25-hydroxyvitamin D (25[OH]D). The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess certainty of evidence.

Results
Electronic searches yielded 37 007 citations, from which we included 151 studies. In children and adolescents, low-certainty evidence suggested reduction in respiratory tract infections with empiric vitamin D. There was no significant effect on select outcomes in healthy adults aged 19 to 74 years with variable certainty of evidence. There was a very small reduction in mortality among adults older than 75 years with high certainty of evidence. In pregnant women, low-certainty evidence suggested possible benefit on various maternal, fetal, and neonatal outcomes. In adults with prediabetes, moderate certainty of evidence suggested reduction in the rate of progression to diabetes. Administration of high-dose intermittent vitamin D may increase falls, compared to lower-dose daily dosing. We did not identify trials on the benefits and harms of screening with serum 25(OH)D.

Conclusion
The evidence summarized in this systematic review addresses the benefits and harms of vitamin D for the prevention of disease. The guideline panel considered additional information about individuals’ and providers’ values and preferences and other important decisional and contextual factors to develop clinical recommendations.
Female Reproductive Factors, Exogenous Hormone use, and Incident Chronic Kidney Disease and end-stage Renal Disease
Authors: Han Wen-Wen , Miao Meng-Yuan , Lyu Jie-Qiong , Tao Hao-Wei , Jia Yi-Ping , Liu Yu-Jie , Wang Jia-Min , Chen Jing-Si , Qin Li-Qiang , Chen Guo-Chong 
Published: June 2024

Abstract

Context
Younger women have a slower progressive loss of kidney function than age-matched men and the sex advantage diminishes after menopause, suggesting a role for female hormones in the development of kidney diseases.

Objective
To examine the relationships of numerous reproductive factors and exogenous hormone use with long-term risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in women.

Methods
A total of 260 108 women without prevalent CKD and ESRD were included. The relationships of various reproductive factors and exogenous hormone use with incident CKD and ESRD were assessed, with multivariable adjustment for potential confounders.

Results
During a median of ∼12.5 years of follow-up, 8766 CKD and 554 ESRD cases were identified. Younger age at first live birth, hysterectomy or bilateral oophorectomy before age 50 years, menopausal before age 45 years, and menopausal hormone therapy initiated before age 50 years was associated with a higher risk of CKD. The relationships of these factors with ESRD were generally consistent with those for CKD. Each 5-year increment in menopausal age was associated with an 11% lower risk of CKD (hazard ratio [HR] = 0.89; 95% CI, 0.87-0.91) and a 13% lower risk of ESRD (HR = 0.87; 95% CI, 0.79-0.95). Each 5-year delay in starting menopausal hormone therapy was associated with a 13% lower risk of CKD (HR = 0.87; 95% CI, 0.84-0.90) and a 15% lower risk of ESRD (HR = 0.85; 95% CI, 0.73-0.99).

Conclusions
Several reproductive characteristics reflecting shorter cumulative exposure to endogenous estrogen or premature exposure to exogenous hormones are associated with a greater risk of CKD and ESRD in women, supporting a potential role of female hormones in renal pathophysiology.
Acromegaly Disease Control Maintained After Switching From Injected Somatostatin Receptor Ligands to Oral Paltusotine
Authors: Gadelha Mônica R , Casagrande Alessandra , Strasburger Christian J , Bidlingmaier Martin , Snyder Peter J , Guitelman Mirtha A , Boguszewski Cesar L , Buchfelder Michael , Shimon Ilan , Raverot Gerald , Tóth Miklós , Mezősi Emese , Doknic Mirjana , Fan Xiaolin , Clemmons David , Trainer Peter J , Struthers R Scott , Krasner Alan , Biller Beverly M K 
Published: June 2024

Abstract

Context
Paltusotine is a nonpeptide selective somatostatin receptor 2 agonist in development as once-daily oral treatment for acromegaly.

Objective
To evaluate the efficacy and safety of paltusotine in the treatment of patients with acromegaly previously controlled with injected somatostatin receptor ligands (SRLs).

Methods
This phase 3, randomized, double-blind, placebo-controlled trial enrolled adults with acromegaly who had IGF-I ≤1.0 times the upper limit of normal (×ULN) while receiving a stable dose of depot octreotide or lanreotide. Patients were switched from injected SRLs and randomized to receive paltusotine or placebo orally for 36 weeks. The primary endpoint was proportion of patients maintaining IGF-I ≤1.0× ULN. Secondary endpoints were change in IGF-I level, change in Acromegaly Symptom Diary score, and maintenance of mean 5-sample GH &lt;1.0 ng/mL.

Results
The primary endpoint was met: 83.3% (25/30) of patients receiving paltusotine and 3.6% (1/28) receiving placebo maintained IGF-I ≤1.0× ULN (odds ratio, 126.53; 95% CI, 13.73-&gt;999.99; P &lt; .0001). Paltusotine was also superior to placebo for all secondary endpoints: mean (± SE) change in IGF-I of 0.04 ± 0.09× ULN vs 0.83 ± 0.1× ULN (P &lt; .0001); mean (± SE) change in Acromegaly Symptom Diary score of −0.6 ± 1.5 vs 4.6 ± 1.6 (P = .02); mean GH maintained at &lt;1.0 ng/mL in 20/23 (87.0%) vs 5/18 (27.8%) patients (odds ratio, 16.61; 95% CI, 2.86-181.36; P = .0003). The most common adverse events were acromegaly symptoms and gastrointestinal effects characteristic of SRLs.

Conclusion
Replacement of injected SRLs by once-daily oral paltusotine was effective in maintaining both biochemical and symptom control in patients with acromegaly and was well tolerated.
Systemic Inflammatory Indices and Liver Dysfunction in Turner Syndrome Patients: A Retrospective Case-control Study
Authors: Zaegel Nadia , Brahimaj Rigleta , Battaglia-Hsu Shyuefang , Lamiral Zohra , Feigerlova Eva 
Published: June 2024

Abstract

Context
Liver function abnormalities have been reported in patients with Turner syndrome (TS); however, the pathophysiological mechanisms have not been well elucidated. Low-grade inflammation has been associated with metabolic dysfunction-associated steatotic liver disease.

Objective
We studied systemic inflammatory indices [aspartate transaminase to lymphocyte ratio index (ALRI), aspartate transaminase to platelet ratio index (APRI), gamma-glutamyl transferase to platelet ratio (GPR), neutrophil-lymphocyte-ratio (NLR), and platelet lymphocyte ratio and examined their associations with the hepatic abnormalities observed in these subjects.

Methods
We performed a retrospective analysis of the medical records of 79 patients with TS (mean age 32.5 ± 9.2 SD years) who were treated at the University Hospital of Nancy. Using matched-pair analyses based on age and body mass index (BMI), we compared 66 patients with TS (25.6 ± 7.3 years; BMI 25.9 ± 6.3 kg/m2) to 66 healthy control participants (24.7 ± 6.8 years; BMI 26 ± 6.7 kg/m2).

Results
Liver function abnormalities were present in 57% of the patients with TS. The ALRI, APRI, GPR, and NLR were significantly greater in patients with TS who presented with liver dysfunction than in patients with TS who had normal liver function. According to the matched-pair analyses, the ALRI, APRI, and GPR were greater in patients with TS than in healthy control participants. Logistic regression revealed that a diagnosis of TS was significantly associated with ALRI, APRI, and GPR and liver dysfunction.

Conclusion
Noninvasive inflammatory indices (ALRI, APRI, and GPR) might be a promising indicators of liver dysfunction in patients with TS. Future prospective studies are needed to confirm our findings and to explore the clinical significance and prognostic value of systemic inflammatory indices in Turner syndrome.
Neuromuscular Emergencies
Authors: Albin Catherine S. W. 
Published: June 2024

ABSTRACT

OBJECTIVE
This article aims to familiarize the reader with the clinical approach, diagnostic considerations, and treatment strategies for patients presenting with abrupt-onset or acutely worsening weakness due to neuromuscular disorders.

LATEST DEVELOPMENTS
Neuromuscular weakness is often the result of an inflammatory process. In recent years, there has been growing recognition of pathologic antibodies that cause neuromuscular injury. This has allowed clinicians to make a more accurate diagnosis. Additionally, neuromuscular junction disorders and myopathies are increasingly identified as the adverse effects of novel anticancer therapies, namely immune checkpoint inhibitors. More data are being incorporated into frameworks for neuroprognostication after neuromuscular emergencies, especially for commonly encountered disorders such as Guillain-Barré syndrome.

ESSENTIAL POINTS
Care of patients with neuromuscular emergencies requires prompt attention to respiratory status. Once supportive measures are in place to protect the airway and facilitate effective ventilation, diagnostic considerations should hinge on appropriate neurologic localization. Aggressive immunosuppression is often required for immune-mediated neuromuscular disorders, and clinicians must be thoughtful in selecting a strategy that best aligns with each patient’s risk factors and comorbidities.