bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel minimally invasive technique of inter-spinal distraction fusion surgery for single-level lumbar spinal stenosis in octogenarians: a retrospective cohort study
Authors: Chen Mengmeng , Jia Pu , Feng Fei , Tang Hai 
Published: February 2022

Abstract
Objective
Surgical treatment of lumbar spinal stenosis (LSS) in octogenarians (patients aged ≥ 80 years) has been a challenge. Inter-spinal distraction fusion (ISDF)—a minimally invasive procedure—was used for treating LSS in octogenarians. This retrospective cohort study aimed to investigate the clinical efficacy and safety of a minimally invasive ISDF technique for LSS in octogenarian patients.

Methods
From April 2015 to April 2019, octogenarian patients who underwent lumbar fusion surgery due to single-segment LSS were included. The patients were grouped into the ISDF group and posterior lumbar interbody fusion (PLIF) group based on the type of surgery. Clinical outcomes were evaluated using scores of the visual analog pain scale (VAS), Oswestry Disability Index (ODI), and Japanese Orthopedics Association (JOA) scale. Radiographs were assessed for the intervertebral angle (IA), lumbar lordosis (LL), and posterior disc height (PDH). After 2 years postoperatively, all patients underwent computed tomography (CT) to evaluate the fusion condition. Perioperative data and related complications were recorded.

Results
Sixty-two patients were included (mean age: 82.22 ± 1.95 years). The ISDF and the PLIF groups had 34 and 28 patients, respectively. The average follow-up time was 2.1 ± 0.25 years. There was no significant difference in VAS, ODI, JOA, and PDH scores between both groups preoperatively and at each postoperative time-point. The IA and LL showed significant differences between both groups after surgery (p < 0.05). The postoperative IA in the ISDF group were significantly lower than the preoperative values, while that in the PLIF group were markedly increased. The PLIF group had an increased LL compared with that preoperatively (p < 0.05), while the LL in the ISDF did not significantly change. The operative time, blood loss, hospital stay time, and the rate of perioperative complications of the ISDF group were significantly lower than those of the PLIF group (p < 0.05). There was no significant difference in the fusion rates between both groups.

Conclusion
ISDF surgery is a viable method for octogenarian patients with LSS that provides a similar clinical efficacy, shorter operative time, less blood loss, shorter hospital stay time, and fewer complications, compared to the PLIF surgery.
CD90 is regulated by notch1 and hallmarks a more aggressive intrahepatic cholangiocarcinoma phenotype
Authors: Mancarella Serena , Serino Grazia , Gigante Isabella , Cigliano Antonio , Ribback Silvia , Sanese Paola , Grossi Valentina , Simone Cristiano , Armentano Raffaele , Evert Matthias , Calvisi Diego F. , Giannelli Gianluigi 
Published: February 2022

Abstract
Background
Intrahepatic Cholangiocarcinoma (iCCA) is characterized by a strong stromal reaction playing a role in tumor progression. Thymus cell antigen 1 (THY1), also called Cluster of Differentiation 90 (CD90), is a key regulator of cell–cell and cell–matrix interaction. In iCCA, CD90 has been reported to be associated with a poor prognosis. In an iCCA PDX model, we recently found that CD90 was downregulated in mice treated with the Notch γ-secretase inhibitor Crenigacestat. The study aims to investigate the role of CD90 in relation to the NOTCH pathway.

Methods
THY1/CD90 gene and protein expression was evaluated in human iCCA tissues and xenograft models by qRT-PCR, immunohistochemistry, and immunofluorescence. Notch1 inhibition was achieved by siRNA. THY1/CD90 functions were investigated in xenograft models built with HuCCT1 and KKU-M213 cell lines, engineered to overexpress or knockdown THY1, respectively.

Results
CD90 co-localized with EPCAM, showing its epithelial origin. In vitro, NOTCH1 silencing triggered HES1 and THY1 down-regulation. RBPJ, a critical transcriptional regulator of NOTCH signaling, exhibited putative binding sites on the THY1 promoter and bound to the latter, implying CD90 as a downstream NOTCH pathway effector. In vivo, Crenigacestat suppressed iCCA growth and reduced CD90 expression in the PDX model. In the xenograft model, Crenigacestat inhibited tumor growth of HuCCT1 cells transfected to overexpress CD90 and KKU-M213 cells constitutively expressing high levels of CD90, while not affecting the growth of HuCCT1 control cells and KKU-M213 depleted of CD90. In an iCCA cohort, patients with higher expression levels of NOTCH1/HES1/THY1 displayed a significantly shorter survival.

Conclusions
iCCA patients with higher NOTCH1/HES1/THY1 expression have the worst prognosis, but they are more likely to benefit from Notch signaling inhibition. These findings represent the scientific rationale for testing NOTCH1 inhibitors in clinical trials, taking the first step toward precision medicine for iCCA.
Pulmonary vein aneurysm in a New Zealand White rabbit: a case report
Authors: Kim Jong-Min , Woo Chang Gok , Kim Sa Hun , Jeong Eui-Suk , Kim Kil-Soo , Kang Byeong-Cheol 
Published: February 2022

Abstract
Background
Pulmonary venous aneurysm (PVA) is a rare condition characterized by aneurysmal dilatation of the pulmonary vein in humans. The diagnosis is incidental usually as there are no clinical symptoms. This case report describes a histological diagnosis of PVA in a New Zealand White rabbit.

Case presentation
A 1.5-kg male New Zealand White rabbit was acclimatized in an animal room for 5 weeks until the experiment began. However, the rabbit was found dead, with signs of nasal hemorrhage. Necropsy revealed tracheal and pulmonary hemorrhage, and the epistaxis had a pulmonary origin. PCR and ELISA to detect antigens and antibodies pertaining to the rabbit hemorrhagic disease virus showed negative results. Multiple ballooning lesions (50–200 μm size) in the pulmonary veins were observed on histological examination, and PVA was diagnosed. Death was attributed to a spontaneous rupture of the PVA and massive hemorrhage into the lung parenchyma that extended into the trachea and nasal passages.

Conclusions
To the author’s best knowledge, this is the first report of a PVA in a rabbit.
High-diagnostic accuracy of inguinal ultrasonography and fine needle aspiration followed by dynamic sentinel lymph node biopsy in men with non-palpable and palpable inguinal lymph nodes.
Authors: Lee Esther Wan Ching , Issa Allaudin , Oliveira Pedro , Lau Maurice , Sangar Vijay , Parnham Arie , Fankhauser Christian Daniel 
Published: February 2022

6 Background: Penile cancer undergoes a stepwise dissemination and metastasises first to the inguinal lymph nodes (ILN). Because men can be cured in this early stage of metastatic disease, early detection and treatment is important. Methods: We performed a retrospective analysis of men with ≥T1G2 penile cancer and negative inguinal US guided FNA undergoing DSNB. Men with suspicious US but negative FNA underwent US guided ILN excision. Men with ≥T1G2 local recurrence during follow-up and non-squamous cell histologies were excluded. Descriptive analysis was performed, and sensitivity and negative predictive values (NPV) were calculated. Results: The final cohort consisted of 403 men with a median age of 65 years (IQR 55-73) and body mass index (BMI) of 28.6 kg/m² (IQR 25-33) for this analysis. This gave 728 groins with negative FNA undergoing DSNB +/- US guided lymph node excision. At least one sentinel node (SN) was visualised in 93% during the 1st and in 7% during the 2nd lymphoscintigraphy. Median SNs visualised preoperatively was 1 and a median of 2 nodes were resected. ILN metastases were detected in 9% groins with non-palpable and in 17% with palpable lymph nodes. Stratified by non-palpable and palpable ILN, non-local recurrence despite pathologically negative DSNBs was observed in 0.5% and 0%. Limited to men with at least 24 months follow-up, non-local recurrence after negative DSNBs was observed in 0.4% and 0%. The sensitivity of DSNB was 96% and NPV was 100%. The main limitation of this analysis is its retrospective nature and inherit biases. Conclusions: Our results suggest that in a high volume centre pre-operative ultrasound +/- FNA and DSNB can be used to accurately stage men with non-palpable and palpable ILN in men with ≥T1G2 penile cancer. Further, FNA in advance of surgery provides logistical and surgical advantages. In those patients with palpable disease but negative FNA, we advocate ultrasound guided excision in case of enlarged or suspicious ILN during DSNB.[Table: see text]
Comparative ctDNA analyses of African-American and Caucasian patients with CRPC.
Authors: Jaeger Ellen B. , Caputo Sydney , Fleming William , Manogue Charlotte , Lieberman Alex , Sussman Isabelle P. , Miller Patrick , Light Malcolm , Huang Minqi , Barata Pedro C. , Lewis Brian E. , Layton Jodi Lyn , Ledet Elisa M. , Sartor A. Oliver 
Published: February 2022

24 Background: Somatic genetic analyses have indicated genetic distinctions in AA as compared to C patients. In the Mahal et al. study (1) evaluating a broad spectrum of pts with tissue based assays, FOXA1 mutations were more frequent in AA men and TP53 mutations were less frequent in AA men as compared to C men. In a separate analysis by Khashab et al. (2) conducted in prostate cancer pts receiving androgen deprivation therapy, using both tissue and ctDNA assays, the authors reported AR, TP53, SPOP, and BRCA2 were more frequently mutated in AA men as compared to C men. Herein we assessed the Guardant 360 platform in assessing ctDNA differences in AA and C men, all of whom had CRPC at the time assays were performed. Methods: Guardant 360 was used to analyze ctDNA with a cut-off of >0.5% for allelic fractions for ascertaining the presence or absence of pathogenic mutations and various amplifications. Lower allelic fractions were not analyzed given these may represent less relevant mutations. Depending on the timing of the assays (2015-2021), 70-83 genes were analyzed. All pts had CRPC and all patients were treated at Tulane Cancer Center. Chi Square analyses were used to determine statistical differences. AR, BRCA2, and TP53 were assessed but SPOP and FOXA1 were not assessable in the Guardant ctDNA assay. Both mutations and amplifications were evaluated. Results: Among men with CRPC, a total of 48 AA men and 179 C men were analyzed using ctDNA. Clear distinctions were found in the alteration reported in APC, TP53, and CDK12. TP53 was less frequently mutated and other genes were more frequently altered in the AA men. Conclusions: Using Guardant ctDNA assays in men with CRPC, clear distinctions were found in AA men as compared to C men. It is unclear why these results differ from that reported by others, however distinctions in both the assays and the populations are notable.[Table: see text]
Association between health-care system and prostate cancer mortality for African American men with localized and metastatic prostate cancer.
Authors: Nelson Tyler J. , Courtney Patrick Travis , Klebaner Daniella , Guram Kripa , Sherer Michael Vincent , Rodrigues De Moraes Gustavo , Banegas Matthew P. , Stewart Tyler F. , McKay Rana R. , Garraway Isla , Murphy James , Rose Brent S. 
Published: February 2022

27 Background: African American (AA) men with prostate cancer (PC) present with more advanced disease and have worse survival than comparable non-Hispanic White (White) men. Recent studies suggest that receiving care within an equal access setting may attenuate these disparities. We hypothesize that AA men receiving care within the Veterans Health Administration (VHA) will have improved outcomes compared to AA men receiving care in the general population as assessed by the Surveillance, Epidemiology, and End Results (SEER) database. Methods: We identified AA men diagnosed with PC between 2004 and 2015 in the VHA and SEER. For comparisons of covariate distributions across subgroups, we used the chi-squared test with continuity correction. We analyzed the cumulative incidence (with 95% confidence intervals (CIs)) of PC specific mortality (PCSM) in the VHA and SEER. Additionally, multivariable Cox proportional hazards models controlling for demographic information were performed. Results: The cohort included 85,409 AA men (VHA: 27,415, SEER: 57,994). Median follow-up was 4.79 years in the VHA and 5.16 years in SEER. In the VHA, AA men were more likely to present with localized disease (VHA 94.7% vs SEER 86.4%, p < 0.001) and less likely to have metastatic disease (3.2% vs 4.3%, p < 0.001). The 5-year cumulative incidence of PCSM was lower for patients in the VHA (VHA: 3.8% [CI: 3.5-4.1%] vs. SEER: 5.0% [CI: 4.8-5.2%], p < 0.001). The PCSM difference was largest in men with metastatic disease. In metastatic patients, cumulative incidence of PCSM at five years was significantly lower in the VHA (VHA 52.5% [CI: 48.0-56.5%] vs. SEER 64.8% [CI: 62.3-67.1%], p < 0.001). In contrast, AA men with localized disease had similar PCSM in the VHA and SEER (VHA 2.4% [CI: 2.2-2.6%] vs. SEER 2.6% [CI: 2.4-2.7%], p = 0.09 at five years). On multivariable analysis, VHA system was associated with lower PCSM [Hazard Ratio (HR): 0.91, p < 0.001]. There was a significant interaction between VHA system and distant metastases at diagnosis [p < 0.001] indicating larger differences in PCSM by healthcare system in metastatic patients as compared to localized patients. VHA system was associated with reduced PCSM in metastatic patients [HR 0.84, p < 0.001] but not in localized patients [HR 0.96, p = 0.13]. Conclusions: AA men in the VHA had a significantly lower incidence of PCSM than those in the SEER database, especially for those who presented with distant metastases at diagnosis. Future work should examine how cost and access to care affect disparities in outcomes for AA men.
Trends in prostate cancer mortality in the United States of America, by state and race, from 1999 to 2019: Estimates from the Centers for Disease Control WONDER database.
Authors: Jani Chinmay , Mouchati Christian , Abdallah Nour , Mariano Melissa , Jani Ruchi Tusharkumar , Salciccioli Justin D , Marshall Dominic C , Singh Harpreet , Shalhoub Joseph , McKay Rana R. 
Published: February 2022

30 Background: In the United States of America (USA), prostate cancer is the most common cancer in men, and it remained the second leading cause of cancer related mortality. It has a disproportionate burden of disease among minorities. In particular, African American (AA) men have a higher incidence and more aggressive disease course. Our study compares trends in prostate cancer mortality in the United States of America (USA) by race and state from 1999 to 2019. Methods: We used the Center for Disease Control (CDC) WONDER database using ICD-10 code C61 to extract mortality data for malignant prostate cancer. Age standardized death rates (ASDRs) are reported per 100,000 population using the USA standard population. ASDRs were divided into American Indian or Alaskan Native, Asian, Black or African American and, Whites and reported by year for each state. Due to the lack of available data in many states, state-wise analyses were done for white and African American men only. We used Joinpoint regression analysis for trends comparison. Results: Between 1999 and 2019, data was analyzed from 50 states of the USA, of which four started collecting data from 2000, one from 2001, one from 2008, and one from 2009. Three states had data until 2018 only. Data was missing for African American men in 17 states. In 2019, ASDR in African American (13.4/100,000) was significantly higher than Whites (7.3/100,000) (p<0.001). The highest ASDR for African American was observed in Nebraska (33.5/100,000), followed by Wisconsin (17.7/100,000). In contrast, the highest ASDR for whites was observed in Alaska (11/100,000), followed by Utah (10.5/100,000) ASDR decreased by 31.8% in White men at the national level, compared to a decline of 44.6% in African American men. ASDR decreased in all states for both races. For White men, the widest drops were in South Dakota (-45.9%) and Kentucky (-47.0%), and the lowest declines in New Hampshire (-11.5%) and Alaska (-16.0%). For African American men, the largest decreases were in Delaware (-57.8%) and Nevada (-55.3%), and the smallest declines were in Kentucky (-14.9%) and Wisconsin (-20.3%). Conclusions: During the last 20 years, the mortality rate from prostate cancer has consistently dropped in all the states of the USA and for all races. Even though a higher decrease in ASDR was observed in the African American and Asian racial groups, ASDR is still higher in African Americans as compared to Whites.[Table: see text]
Tailoring 4Kscore thresholds to multiparametric MRI results.
Authors: Nemirovsky Daniel R , Reddy Akshay G , McSweeney Benjamin , Klose Charles , Chen Joyce , Atienza Matthew , Haji-Momenian Shawn , Imtiaz Danish , Whalen Michael Joseph 
Published: February 2022

31 Background: 4Kscore was developed and validated agnostic to prostate multiparametric MRI (mpMRI) findings, with current clinical paradigms utilizing a value of 7.5% to delineate the potential for high-grade disease. A growing body of evidence suggests improved diagnostic utility when used in conjunction with mpMRI results. Incorporation of mpMRI PIRADS scores may have potential to enhance diagnostic accuracy of 4Kscore, especially for non-definitive lesions. This study aims to examine the optimal 4Kscore threshold in PIRADS 3/4 lesions to maximize test utility and help guide clinical decision-making. Methods: A single-institution review of all patients with recorded 4Kscore, prostate MRI with dominant PIRADS 3/4 lesions, and final biopsy pathology from 2016-2020 was conducted from an IRB-approved database. Clinically significant prostate cancer (csPCa) was defined as Gleason score ≥3+4 on final biopsy. Receiver operating characteristic curves were generated, and the primary data point was chosen to maximize sensitivity and specificity. Results: 88 patients with dominant PIRADS 3 (n = 40) or PIRADS 4 (n = 48) lesions were identified. For patients with PIRADS 3 lesions, area under the curve (AUC) was 0.8083 (p < 0.0039) with optimal 4Kscore threshold to detect csPCa as 18.5% (sensitivity = 70.00%, specificity = 80.00%). Negative predictive value (NPV) at 4Kscore of 18.5% in PIRADS 3 lesions was 0.93. In patients with dominant PIRADS 4 lesions, AUC was 0.7735 (p < 0.002), and optimal threshold to detect csPCa was 21.5% (sensitivity = 70.59%, specificity = 76.67%). NPV at 4Kscore of 21.5% in PIRADS 4 lesions was 0.82. Conclusions: Stratification of mpMRI PIRADS 3/4 lesions suggests that utilization of more permissive 4Kscore thresholds can improve prediction of csPCa without sacrificing NPV, especially for PIRADS 3 lesions. These findings may enhance risk-adapted prostate cancer screening, reduce unnecessary prostate biopsies, and optimize clinical management.
Outcome of patients with PSMA-PET/CT screen failure by VISION criteria and treated with 177Lu-PSMA therapy.
Authors: Hotta Masatoshi , Gafita Andrei , Czernin Johannes , Calais Jeremie 
Published: February 2022

39 Background: The VISION trial showed that 177Lu-PSMA can prolong survival and improve the quality of life of patients with advanced mCRPC. The VISION trial used PSMA-PET/CT to select patients for inclusion. Here, we evaluated the outcome of patients treated with 177Lu-PSMA who would have been screen failure (SF) by VISION-PET criteria. Methods: We conducted a retrospective cohort study in our institutional database of patients treated with ≥1 cycle of 177LuPSMA between November 2017 and July 2021 (n = 74) and a multicenter dataset published previously (n = 230) (Gafita A, Lancet Oncol 2021). One dual certified reader (M.H.) in nuclear medicine and radiology blinded for patient outcomes reviewed the baseline PSMA-PET/CT scans to define eligible (VISION-PET-E) vs SF (VISION-PET-SF) patients. VISION-PET- SF criteria were defined as:1) absence of metastatic lesion with uptake > liver background (i.e., low PSMA expression) or 2) presence of ≥ 1 metastatic lesion measurable by CT (≥ 1 cm for bone lesions with soft-tissue component (M1b) and solid/visceral organs lesions (M1c); ≥ 2.5 cm for lymph nodes lesions (N1-M1a)) with uptake ≤ liver background (i.e., PSMA-negative lesions). Outcome measures included PSA response rates (decline of ≥50% (PSA50RR) and any decline (anyPSARR)), PSA-progression free-survival (PSA-PFS), and overall survival (OS). Results: 3/304 patients (1%) were excluded (lost to follow-up (n = 2), missing DICOM CT images (n = 1)). 272/301 (90.4%) of the analyzed patients were VISION-PET-E while 29/301 (9.6%) were VISION-PET-SF: 8/301 (2.7%) with low PSMA expression and 21/301 (7.0%) with PSMA-negative lesions, respectively. The median follow-up time was 12.6 months (IQR: 7.0-21.3, range: 0.6-62.3). VISION-PET-SF patients had a worse PSA50RR (21% vs 50%; p = 0.005), anyPSARR (41% vs 71%; p = 0.003), median PSA PFS (2.1 months (1.1-3.3) vs. 4.1 (4.0-5.8); p = 0.023)), and tended to have a shorter median OS (9.6 months (4.7-14.0) vs. 14.2 (12.6-15.9); p = 0.16) than the VISION-PET-E patients. Patients with PSMA-negative lesion (n = 21) tended to have a worse response than those with low PSMA expression (n = 8): median OS 8.2 months (4.4-11.0) vs. NA (11.1-NA) (p = 0.034), median PSA-PFS 1.8 months (1.4-3.3) vs. 2.8 (1.1-5.7) (p = 0.44), PSA50RR 19% vs 25% (p = 1.00), and any PSARR 38% vs 50% (p = 0.68). Conclusions: Some have argued that the low SF rate of 12.6% (126/1003) in the VISION trial may obviate the need for PSMA-PET eligibility screening prior to 177Lu-PSMA. Here we report that VISION-PET-SF patients had worse outcomes than VISION-PET-E patients in response to 177Lu-PSMA therapy. The best management of patients with negative or low PSMA expressing lesions is unknown. Combining 177Lu-PSMA with external-beam RT and/or with other systemic therapy may be an effective therapeutic approach. Refinements in patient selection for 177Lu-PSMA are needed to optimize patient outcomes.