bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timing of immunotherapy in stage IV non-small cell lung cancer.
Authors: Komiya Takefumi , Zhu Junjia , Takamori Shinkichi , Greenberg Max 
Published: June 2024

8544 Background: Excluding oncogene-driven disease, a combination of cytotoxic chemotherapy and immune checkpoint inhibitor (i.e., anti-PD1/PDL1 inhibitors) became a standard management in stage IV non-small cell lung cancer (NSCLC) in 2017. Cases with a positive driver oncogene such as EGFR, however, need to be treated with rather appropriate targeted therapy. In routine practice, a lengthy turnaround time of molecular analysis to rule out oncogenes makes the chemo-immunotherapy combination a challenge. In addition, unexpected toxicities when immunotherapy and targeted therapy are combined or sequenced have been reported. Because of these restrictions many oncologists often initiate traditional chemotherapy alone for the first few cycles until molecular result becomes available so that they can modify the first-line therapy accordingly. This practice pattern to delay initiation of immunotherapy may lead to inferior cancer outcome. Keynote-189, an international phase III trial defining the role of additive pembrolizumab to first-line chemotherapy, demonstrated an overall survival advantage of chemo-immunotherapy combination over chemotherapy alone regardless of PDL1 status. In the arm of chemotherapy alone, an approximately 40% of patients received immunotherapy as second-line therapy. Despite the cross-over of the arms, this study showed a statistically significant difference in OS, suggesting the importance of early exposure to immunotherapy. Impact of delayed administration of immunotherapy in the first-line therapy is unknown. Methods: Using NCDB, a total of 99,008 patients diagnosed in 2017-2018 as stage IV NSCLC were screened. Eligible patients must have been treated with multi-agent chemotherapy as first-course of therapy. Those with neuroendocrine pathology, those who were exposed to immunotherapy prior to chemotherapy were excluded. They were assigned to a group of: (1) those who received immunotherapy within 30 days of chemotherapy, (2) 30-61 days of chemotherapy, or (3) chemotherapy alone. Those who have died within 2 months of diagnosis were excluded. Results: A total of 3291, 237, and 4309 were selected for group 1, 2, 3 for the analysis, respectively. Median OS was 14.5, 9.5, and 10.0 months for the group 1,2, 3, respectively. The significant difference in OS was observed between group 1 and 2 (HR= 0.74, 95% CI: 0.64-0.87, p=0.0003) and between group 1 and 3 (HR=0.73, 95%CI 0.70-0.78, p<0.0001). There is no difference in OS between group 2 and 3. Multivariate analysis demonstrated that group 1 has a significantly prolonged OS over group 2. The significant OS difference between group 1 and 2 was confirmed by propensity-score matching analysis (N=237 each, HR=0.73, 95%CI: 0.59-0.90, p=0.004). Conclusions: This retrospective study using one of the largest cancer databases suggests that delay of immunotherapy when used in combination with chemotherapy have detrimental effect in survival outcome.
Intracranial outcomes of 1L selpercatinib in advanced RET fusion-positive NSCLC: LIBRETTO-431 study.
Authors: Perol Maurice , Goto Koichi , Solomon Benjamin J. , Park Keunchil , Nadal Ernest , Bria Emilio , Martin Claudio , Bar Jair , Williams Justin , Puri Tarun , Li Jian , Uh Minji , Lin Boris K. , Zhou Caicun 
Published: June 2024

8547 Background: Selpercatinib is a highly selective and potent CNS active RET inhibitor approved for treatment of advanced RET fusion-positive ( RET+) NSCLC. Treatment or prevention of CNS disease is critical in RET+ NSCLC patients (pts), who have nearly a 50% lifetime prevalence of brain metastases (mets) (Drilon et al. JTO 2018). LIBRETTO-431 is the first study to compare intracranial (IC) efficacy of a targeted therapy to chemo/IO in pts with oncogene driven NSCLC. Methods: LIBRETTO-431 (NCT04194944) is a randomized, open-label, phase 3 trial comparing 1L selpercatinib vs chemotherapy (cisplatin/carboplatin + pemetrexed) +/- pembrolizumab. As previously reported, the study met its primary endpoint of PFS by blinded independent central review (BICR) at the pre-planned interim analysis. IC analyses included CNS and non-CNS PD, IC PFS and IC responses by BICR per RECIST 1.1 in all pts who had a baseline and one or more post-baseline CNS scans (CNS-evaluable) and were designated to receive pembrolizumab if randomized to the control arm (CNS-pembro population). Adverse events were evaluated in the CNS safety population. Results: A total of 192 of 261 pts enrolled were CNS-evaluable (selpercatinib: 120, control: 72). Baseline characteristics were generally balanced with the selpercatinib arm having a slightly lower proportion of pts with BICR-assessed baseline brain mets (21% vs 25%) and prior CNS radiotherapy (RT; 6% vs 10%) compared to the control arm. Selpercatinib delayed CNS PD as evidenced by a lower 12 mo cumulative incidence rate (CIR) for CNS PD, as well as delaying non-CNS PD compared to control in pts with and without brain mets (Table). In pts with measurable brain mets at baseline (n=29), median time to IC response per RECIST 1.1 was similar between selpercatinib and control (1.4 mo [range: 1.2-2.9] vs 1.6 mo [range: 1.2-2.9]); however, as previously reported the IC response rates were higher (82% vs 58%) and more durable (12 mo DOR rate 76% vs 63%) with selpercatinib vs control (Zhou et al. NEJM 2023). IC responses to selpercatinib were more common in pts without prior CNS RT (14/15, 93%) than with prior CNS RT (3/6, 50%). Conclusions: Selpercatinib delayed IC progression in advanced RET+ NSCLC pts with or without baseline brain mets and achieved higher IC response rates compared to chemotherapy + pembrolizumab. LIBRETTO-431 is the first study to demonstrate IC efficacy improvement of a targeted therapy vs chemo/IO in a biomarker selected NSCLC population. These data further support selpercatinib as the preferred 1L regimen in pts with advanced RET+ NSCLC. Clinical trial information: NCT04194944 . [Table: see text]
Clinical Utility of Tumor Next-Generation Sequencing Panel Testing to Inform Treatment Decisions for Patients With Advanced Solid Tumors in a Tertiary Care Center
Authors: Bogdan Lucia , Saleh Ramy R. , Avery Lisa , Del Rossi Samanta , Yu Celeste , Bedard Philippe L. 
Published: June 2024

PURPOSE There is limited information about the clinical utility of targeted next-generation sequencing (NGS) panel testing to inform decision making for patients with advanced solid tumors. The Ontario-wide Cancer Targeted Nucleic Acid Evaluation (OCTANE) is a prospective study that enrolled more than 4,500 patients with solid tumor for NGS panel testing. We performed a retrospective survey of medical oncologists to evaluate the impact of NGS testing on treatment decisions. METHODS Patients and treating oncologists were identified at the Princess Margaret Cancer Center between 2016 and 2021. Tumor-only sequencing was performed using a gene panel of either 555 or 161 cancer genes. Oncologists were asked to review testing results and complete a survey indicating whether NGS testing affected treatment decisions. The primary outcome of this study was rate of treatment change on the basis of mutation results. Patient, test, and physician factors were evaluated for association with treatment changes using univariate analyses and a mixed-effects model. RESULTS Of the 582 surveys sent, 394 (67.7%) were completed. We found that 188 (47.7%) patients had testing results classified as actionable by the oncologist and 62 (15.7%) patients were matched to treatment, of whom 37 (60%) were enrolled in a clinical trial, 13 (21%) received an approved drug, four (6%) were prescribed off-label therapy, and eight (13%) avoided ineffective treatment. Patient, test, and physician characteristics were not significantly associated with treatment change. There was no difference in overall survival between patients who received matched treatment versus those who did not ( P = .55, median survival not reached). CONCLUSION OCTANE testing led to a change in drug treatment in 15.7% of patients, supporting the clinical utility of NGS panel testing for patients with advanced solid tumors.
Adult expression of the cell adhesion protein Fasciclin 3 is required for the maintenance of adult olfactory interneurons
Authors: Vaikakkara Chithran Aarya , Allan Douglas W. , O'Connor Timothy P. 
Published: June 2024

ABSTRACT
The proper functioning of the nervous system is dependent on the establishment and maintenance of intricate networks of neurons that form functional neural circuits. Once neural circuits are assembled during development, a distinct set of molecular programs is likely required to maintain their connectivity throughout the lifetime of the organism. Here, we demonstrate that Fasciclin 3 (Fas3), an axon guidance cell adhesion protein, is necessary for the maintenance of the olfactory circuit in adult Drosophila. We utilized the TARGET system to spatiotemporally knockdown Fas3 in selected populations of adult neurons. Our findings show that Fas3 knockdown results in the death of olfactory circuit neurons and reduced survival of adults. We also demonstrated that Fas3 knockdown activates caspase-3-mediated cell death in olfactory local interneurons, which can be rescued by overexpressing baculovirus p35, an anti-apoptotic protein. This work adds to the growing set of evidence indicating a crucial role for axon guidance proteins in the maintenance of neuronal circuits in adults.
Prediction of Isolated Local Recurrence After Resection of Pancreatic Ductal Adenocarcinoma: A Nationwide Study
Authors: van Goor I. W. J. M. , Andel P. C. M. , Buijs F. S. , Besselink M. G. , Bonsing B. A. , Bosscha K. , Busch O. R. , Cirkel G. A. , van Dam R. M. , Festen S. , Koerkamp B. Groot , van der Harst E. , de Hingh I. H. J. T. , Kazemier G. , Liem M. S. L. , Meijer G. , de Meijer V. E. , Nieuwenhuijs V. B. , Roos D. , Schreinemakers J. M. J. , Stommel M. W. J. , Wit F. , Verdonk R. C. , van Santvoort H. C. , Molenaar I. Q. , Intven M. P. W. , Daamen L. A. ,   The Dutch Pancreatic Cancer Group
Published: June 2024

Abstract
Background
Distinguishing postoperative fibrosis from isolated local recurrence (ILR) after resection of pancreatic ductal adenocarcinoma (PDAC) is challenging. A prognostic model that helps to identify patients at risk of ILR can assist clinicians when evaluating patients’ postoperative imaging. This nationwide study aimed to develop a clinically applicable prognostic model for ILR after PDAC resection.

Patients and Methods
An observational cohort study was performed, including all patients who underwent PDAC resection in the Netherlands (2014–2019; NCT04605237). On the basis of recurrence location (ILR, systemic, or both), multivariable cause-specific Cox-proportional hazard analysis was conducted to identify predictors for ILR and presented as hazard ratios (HRs) with 95% confidence intervals (CIs). A predictive model was developed using Akaike’s Information Criterion, and bootstrapped discrimination and calibration indices were assessed.

Results
Among 1194/1693 patients (71%) with recurrence, 252 patients (21%) developed ILR. Independent predictors for ILR were resectability status (borderline versus resectable, HR 1.42; 95% CI 1.03–1.96; P = 0.03, and locally advanced versus resectable, HR 1.11; 95% CI 0.68–1.82; P = 0.66), tumor location (head versus body/tail, HR 1.50; 95% CI 1.00–2.25; P = 0.05), vascular resection (HR 1.86; 95% CI 1.41–2.45; P < 0.001), perineural invasion (HR 1.47; 95% CI 1.01–2.13; P = 0.02), number of positive lymph nodes (HR 1.04; 95% CI 1.01–1.08; P = 0.02), and resection margin status (R1 < 1 mm versus R0 ≥ 1 mm, HR 1.64; 95% CI 1.25–2.14; P < 0.001). Moderate performance (concordance index 0.66) with adequate calibration (slope 0.99) was achieved.

Conclusions
This nationwide study identified factors predictive of ILR after PDAC resection. Our prognostic model, available through www.pancreascalculator.com, can be utilized to identify patients with a higher a priori risk of developing ILR, providing important information in patient evaluation and prognostication.
KAJIAN KEHILANGAN AIR PERUMDA DELTA TIRTA PADA DMA SHOJI LAND CABANG PORONG
Authors: Hasna Salsabila , Purnomo Alfan 
Published: June 2024

Kehilangan air batas maksimum berdasarkan Peraturan Menteri Pekerjaan Umum dan Perumahan Rakyat Republik Indonesia No 27/PRT/M/2016 yaitu sebesar 20 %, sedangkan Perusahaan Umum Daerah Delta Tirta, kehilangan air melebihi batas maksimum 32%. Dilakukan kajian terhadap Distric Meter Area (DMA) Shoji Land Cabang Porong dengan persen kehilangan air sebesar 56% di Bulan Juli 2023. Tujuan dari penelitian ini yakni menghitung nilai kerugian finasial akibat kehilangan air dan merancang solusi perbaikan berdasarkan penyebab terjadinya kehilangan air berdasarkan neraca air. pada hasil penelitian didapatkan hasil persen kehilangan air bulan Oktober sebesar 51% dengan persen kehilangan air fisik sebesar 31,4% dan 19,4% untuk kehilangan air non-fisik. Hasil rata rata kerugian finansial akibat kehilangan air bulan Agustus-Oktober sebesar Rp. 31.897.659/bulan. Sehingga, diperlukannya desian berdasarkan penyebab kehilangan air, yaitu kebocoran air, ketidakakurasian meter zoning, dan ketidakakurasian meter sambungan rumah. Oleh karena itu, strategi penggantian dan tera ulang meter air serta perbaikan pipa diimplementasikan untuk mengatasi masalah ini berdasarkan data neraca air bulan Oktober.
Imaging findings of breast leukaemia: a case series
Authors: Li Dandan , Xin Yuwei , Zhu Jiaan 
Published: June 2024

Aims/Background Breast leukaemia (BL) is a rare breast malignancy that is treated differently from other malignant conditions. However, it is easily confused with other conditions; therefore, how to accurately diagnose is crucial. We retrospectively analysed the imaging findings of 13 patients to provide a diagnostic reference. Methods From January 2015 to April 2023, 13 patients with BL confirmed by biopsy who underwent imaging in Peking University People’s hospital were retrospectively analysed. The imaging findings obtained via ultrasound (US), mammography (MMG), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT) were analysed, and the detection rates of these methods for diagnosing BL were compared. Results Twenty-nine lesions were detected in the 13 patients. These patients presented with palpable masses or breast swelling several months after treatment for leukaemia, mainly involving the bilateral breasts. Ultrasonography was performed for 13 patients, and all lesions were detected. Most of the identified masses were hypoechoic and had indistinct boundaries, irregular shapes, no enhancement of the posterior echo, and no abundant blood flow. MMG was performed for five patients, revealing breast masses, architectural distortion, and no abnormalities. MRI was performed for four patients, and all lesions were detected; most of the lesions were hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging and diffusion-weighted imaging, with a decreased apparent diffusion coefficient and inhomogeneous enhancement. The enhancement curves were mostly inflow patterns. PET/CT was performed for four patients; two patients had hypermetabolism, and the other two had no obvious radioactive uptake. Conclusion Compared to MMG and PET/CT, US and MRI have higher detection rates. Furthermore, compared to MRI, US is inexpensive, convenient and efficient; therefore, it should be the first choice for diagnosing BL.
Ultrasound-guided serratus anterior plane block enhances postoperative analgesia and recovery in thoracoscopic surgery
Authors: Zhang Jing-Jing , Wang Shao-Lin , He Lei , Yang Ding-Dong , Qian Wei , Zhao Ying 
Published: June 2024

BACKGROUND
The serratus anterior muscle, located in the lateral aspect of the thorax, plays a crucial role in shoulder movement and stability. Thoracoscopic surgery, while minimally invasive, often results in significant postoperative pain, complicating patient recovery and potentially extending hospital stays. Traditional anesthesia methods may not adequately address this pain, leading to increased complications such as agitation due to inadequate pain management.
AIM
To evaluate the application value of ultrasound-guided serratus anterior plane block (SAPB) in patients undergoing thoracoscopic surgery, focusing on its effects on postoperative analgesia and rehabilitation.
METHODS
Eighty patients undergoing thoracoscopic surgery between August 2021 and December 2022 were randomly divided into two groups: An observation group receiving ultrasound-guided SAPB and a control group receiving standard care without SAPB. Both groups underwent general anesthesia and were monitored for blood pressure, heart rate (HR), oxygen saturation, and pulse. The primary outcomes measured included mean arterial pressure (MAP), HR, postoperative visual analogue scale (VAS) scores for pain, supplemental analgesic use, and incidence of agitation.
RESULTS
The observation group showed significantly lower cortisol and glucose concentrations at various time points post-operation compared to the control group, indicating reduced stress responses. Moreover, MAP and HR levels were lower in the observation group during and after surgery. VAS scores were significantly lower in the observation group at 1 h, 4 h, 6 h, and 12 h post-surgery, and the rates of analgesic supplementation and agitation were significantly reduced compared to the control group.
CONCLUSION
Ultrasound-guided SAPB significantly improves postoperative analgesia and reduces agitation in patients undergoing thoracoscopic surgery. This technique stabilizes perioperative vital signs, decreases the need for supplemental analgesics, and minimizes postoperative pain and stress responses, underscoring its high application value in enhancing patient recovery and rehabilitation post-thoracoscopy.
Evaluation of the effectiveness of preventive nursing measures for pressure injuries in patients in the neurology intensive care unit
Authors: Zhang Rong , Ma Peng-Xin , Zhang Juan-Juan 
Published: June 2024

BACKGROUND
Patients in neurology intensive care units (ICU) are prone to pressure injuries (PU) due to factors such as severe illness, long-term bed rest, and physiological dysfunction. PU not only causes pain and complications to patients, but also increases medical burden, prolongs hospitalization time, and affects the recovery process.
AIM
To evaluate and optimize the effectiveness of pressure injury prevention nursing measures in neurology ICU patients.
METHODS
A retrospective study was conducted, and 60 patients who were admitted to the ICU of the Department of Neurology were selected and divided into an observation group and a control group according to the order of admission, with 30 people in each group. The observation group implemented pressure injury prevention and nursing measures, while the control group adopted routine care.
RESULTS
Comparison between observation and control groups following pressure injury prevention nursing intervention revealed significantly lower incidence rates in the observation group compared to the control group at 48 h (8.3% vs 26.7%), 7 d (16.7% vs 43.3%), and 14 d (20.0% vs 50.0%). This suggests a substantial reduction in pressure injury incidence in the observation group, with the gap widening over time. Additionally, patients in the observation group exhibited quicker recovery, with a shorter average time to get out of bed (48 h vs 72 h) and a shorter average length of stay (12 d vs 15 d) compared to the control group. Furthermore, post-intervention, patients in the observation group reported significantly improved quality of life scores, including higher scores in body satisfaction, feeling and function, and comfort (both psychological and physiological), indicating enhanced overall well-being and comfort following the implementation of pressure injury prevention nursing measures.
CONCLUSION
Implementing pressure injury preventive care measures for neurology ICU patients will have better results.
Clinical efficacy of magnetic vibration magnetoelectric therapy in the treatment of chronic prostatitischronic pelvic pain syndrome
Authors: Zhang Zi-Heng , Chang Feng-Juan , Chen Yun 
Published: June 2024

BACKGROUND
The prominent symptoms of chronic pelvic pain syndrome (CPPS) are urogenital pain, lower urinary tract symptoms, psychological problems, and sexual dysfunction. Traditional pharmacological treatments have poor efficacy and more untoward reaction and complications. Magnetic vibration magnetoelectric therapy is a non-invasive form of physiotherapy. Nevertheless, its effectiveness in improving urinary discomfort and relieving pain in patients requires further exploration.
AIM
To investigate the clinical efficacy of the magnetic vibration magnetoelectric therapy instrument in the treatment of chronic prostatitis (CP)/ CPPS.
METHODS
Seventy patients with CP/CPPS were collected from the outpatient clinic and ward of the Department of Male Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, and were treated with magnetic vibration magnetoelectric therapy once a day for a period of 14 d. National Institutes of health-chronic prostatitis symptom index (NIH-CPSI), international index of erectile function 5 (IIEF-5), premature ejaculation diagnostic tool (PEDT), generalized anxiety disorder (GAD), patient health questionnaire, the pain catastrophizing scale (PCS) and traditional Chinese medicine syndrome (TCMS) scores were performed before and after treatment.
RESULTS
The total effective rate of treatment was 58.5%, and the total NIH-CPSI score, pain symptoms, voiding symptoms, quality of life, IIEF-5, PEDT, GAD, PCS and TCMS scores all decreased significantly (P < 0.05).
CONCLUSION
Magnetic vibration magnetotherapy is effective in improving urinary discomfort, relieving pain, improving quality of life, improving sexual dysfunction and relieving negative emotions such as anxiety in patients with CP/CPPS.