tbuckley/cabot-search huggingface dataset:
New method of hepatic artery reconstruction after its injury or resection.
Authors: Oksana V. Katelnitskaya, Oleg I. Kit, Yuriy A. Gevorkyan, Aleksandr V. Snezhko, Oleg Yu. Kaymakchi, Evgeniy N. Kolesnikov, Natalya V. Soldatkina, Vladimir E. Kolesnikov, Andrey V. Dashkov, Sergey I. Poluektov, Maksim K. Aleksandrovich, Dmitry O. Kaymakchi, Vladislav K. Pavlov, Maksim A. Vereshchak, Dmitriy A. Savchenko, Roman E. Tolmakh
Journal: Journal of Clinical Oncology (2021)

e16221 Background: Restoration the hepatic arterial blood flow is required in traumatic or iatrogenic damage to the hepatic artery and its branches, as well as in the planned resection of the hepatic artery with subsequent reconstruction. Various ways have been proposed to solve this problem: ligation of the hepatic artery and its branches, which is associated with an extremely high mortality rate, reaching 70%, and the need for extensive liver resections; portal vein arteriolization; transposition of the splenic artery with its severe complications (heart attack, abscess) or hepatic artery replacement sometimes are not available and imply aggressive anticoagulant therapy, which is often challenging after extensive oncological interventions. Prosthetic vascular grafts are associated with a high risk of infection. We propose replacement of the common hepatic artery defect by transposition of the left gastric artery and end-to-end anastomosis between the proximal end of the left gastric artery and the distal end of the hepatic artery. Methods: The proposed method was applied in 7 cancer patients - 4 cases of iatrogenic damage to the common hepatic artery in lymph node dissection of the hepatoduodenal ligament and 3 resection of the common hepatic artery with tumor infiltration. The mean age of patients was 53 years. 2 patients had surgery for gastric cancer, 5 - pancreatic cancer. Results: The vascular reconstruction lasted for 17 minutes. No thrombotic complications of the reconstruction area or liver necrosis in the postoperative period were registered. The main advantages of this method were the absence of synthetic materials or deficit blood supply to neighboring organs, and no need for extensive mobilization of the great vessels in other areas (renal artery, abdominal aorta). Conclusions: The proposed method for reconstruction of the hepatic artery allows performing a simple and adequate restoration of the hepatic arterial blood flow, reduced time of the vascular stage of the surgery and reduced incidence of postoperative complications associated with the vascular stage - reduced time of liver ischemia and reduced risk of thrombosis in the reconstruction area.
Long-term outcomes of patients with node-negative (N0), triple-negative breast cancer (TNBC) who did not receive adjuvant chemotherapy according to stromal TILs (sTILs).
Authors: Roberto Antonio Leon-Ferre, Jodi M Carter, David W. Hillman, Kathleen S. Tenner, David Zahrieh, Minetta C. Liu, James N. Ingle, Krishna R. Kalari, Daniel W. Visscher, Judy Caroline Boughey, Fergus Couch, Matthew P. Goetz
Journal: Journal of Clinical Oncology (2021)

548 Background: sTILs are a well-established prognostic and predictive biomarker in patients with operable TNBC receiving pre or postoperative systemic therapy. We 1 and others 2,3 have also shown that sTILs are prognostic in patients who did not receive adjuvant chemotherapy. Here, we detail the outcomes of systemically untreated patients with N0 TNBC according to sTIL score. We focused on the N0 subset as a group of patients who may be candidates for future prospective therapy de-escalation trials. Methods: From a clinically annotated cohort of 605 patients with centrally confirmed TNBC (ER/PR &lt; 1% and HER2 negative) with long-term outcomes data, we identified 182 patients treated with locoregional therapy only (breast surgery +/- radiation therapy and no chemotherapy). The clinicopathological characteristics of this cohort have previously been published 1 . In this analysis, we report the 5- and 10-year invasive disease-free survival (iDFS) and overall survival (OS) rates of patients with N0 TNBC according to sTIL levels. IDFS and OS were defined as per the STEEP classification and estimated using the Kaplan–Meier method. Comparisons of the survival distributions between groups were assessed by the log-rank test. sTILs were assessed as a continuous parameter according to the International TIL Working Group guidelines. For comparisons of outcomes between groups, tumors were classified as lymphocyte-predominant TNBC (defined as containing ≥50% sTILs) vs non-lymphocyte-predominant ( &lt; 50% sTILs). Results: Of 182 systemically untreated patients, 149 (82%) were N0 and most (78%) were post-menopausal. T stage distribution was T1: 68%, T2: 28%, T3/4: 4%. Among N0 patients, 31 (21%) had lymphocyte-predominant TNBC, and in this group the 5-year iDFS and OS were 89% (95% CI 76-100) and 96% (95% CI 89-100), while the 10-year iDFS and OS were 89% (95% CI 76-100) and 87% (95% CI 73-100), respectively. In contrast, outcomes for patients with non-lymphocyte predominant TNBC were significantly worse. For this group, 5-year iDFS and OS were 62% (95% CI 53-73) and 78% (95% CI 71-86) while the 10-year iDFS and OS were 45% (95% CI 36-58) and 66% (95% CI 68-76), respectively ( log-rank p = 0.02 for iDFS and log-rank p = 0.03 for OS). Conclusions: sTIL quantification identifies a subset of patients with early-stage N0 TNBC with an exceedingly good prognosis, even in the absence of adjuvant chemotherapy. These data provide support for the evaluation of sTILs as part of prospective investigation of systemic therapy de-escalation strategies in N0 TNBC. References: 1 Leon-Ferre et al, Breast Cancer Res Treat (2018) 167:89-99 2 Park et al, Ann Oncol (2019) 12:1941-1949 3 De Jong et al, ESMO 2020
Inositol‐Requiring Enzyme 1α–Mediated Synthesis of Monounsaturated Fatty Acids as a Driver of B Cell Differentiation and Lupus‐like Autoimmune Disease
Authors: Yana Zhang, Ming Gui, Yajun Wang, Nikita Mani, Shuvam Chaudhuri, Beixue Gao, Huabin Li, Yashpal S. Kanwar, Sarah A. Lewis, Sabrina N. Dumas, James M. Ntambi, Kezhong Zhang, Deyu Fang
Journal: Arthritis & Rheumatology (2021)

To explore the molecular mechanisms underlying dysregulation of lipid metabolism in the pathogenesis of systemic lupus erythematosus (SLE).
Levels of the IGF system components in malignant lesions of the lungs with preventive effect of 1,3-diethylbenzimidazolium triiodide in the experiment.
Authors: Lidia K. Trepitaki, Irina V. Kaplieva, Elena M. Frantsiyants, Viktoriya L. Volkova, Dmitry A. Kharagezov, Igor A. Leyman, Oleg N. Stateshny, Anton G. Milakin
Journal: Journal of Clinical Oncology (2021)

e15095 Background: The system of insulin-like growth factors (IGF) is involved in carcinogenesis, since it promotes proliferation and survival of tumor cells. The purpose of the study was an analysis of the dynamics of the IGF system components in the lungs of rats with antitumor effect of 1,3-diethylbenzimidazolium triiodide. Methods: The main group included male (n=27) and female (n=27) white outbred rats with sarcoma 45 inoculated into the subclavian vein (2×10 6 cells in 0.5 mL saline) but not developed in the lungs due to administration of 1,3-diethylbenzimidazolium triiodide (intragastrically, 0.4 mg/kg once a day according to the regimen: administration for 5 days with a 2-day interval). Control group included males (n=14) and females (n=14) with sarcoma 45 growing in the lungs without treatment. Intact groups included 5 males and 5 females. After 4, 5 and 8 weeks of the experiment animals were decapitated, and levels of IGFI, IGFII, IGFBP1, IGFBP2 and IGFBP3 were measured by ELISA in 10% lung homogenates (CUSABIO BIOTECH Co., Ltd., China). Results: The sarcoma development in the lung was accompanied by the IGFI increase by 2.4-3.0 times in males and by 4.3 times in females, and the opposite IGFII dynamics: an increase in males (by 4.6 times) and decrease in females (by 4.3 times), together with the IGFBP decline. 1,3-diethylbenzimidazolium triiodide upregulated IGFI levels in the lungs of all rats on average by 1.3 times (p&lt;0.05) and normalized IGFII in males, while increasing it in females by 1.6 times (p&lt;0.05), together with higher (compared to controls) IGFBP levels. Conclusions: Preventive antitumor effect of 1.3-diethylbenzimidazolium triiodide is based on the stabilization of the IGF system grossly altered during the malignant process development in the lung.
Abstract 17088: Use of Intracoronary Nicardipine to Reverse Spontaneous Coronary Slow Flow
Authors: Hetal H Mehta, Mackenzie Morris, David Fischman, John Finley, Nicholas Ruggiero, Paul Walinsky, Melissa McCarey, Michael Savage
Journal: Circulation (2017)

Introduction: An under-recognized cause of chest pain and acute coronary syndromes, the coronary slow flow (CSF) phenomenon is characterized by delayed coronary opacification during diagnostic angi...
Trends of cancer associated with modifiable behavior in the U.S.: Is there a difference based on age, gender, or race?
Authors: Cheng-I Liao, Michelle Ann P. Caesar, Chloe Chan, Michael Richardson, Daniel Stuart Kapp, Alex Andrea Francoeur, John Chan
Journal: Journal of Clinical Oncology (2021)

1542 Background: To examine trends in modifiable behaviorally related cancers among men and women in the United States. Methods: Data were obtained from the United States Cancer Statistics (USCS) database for all cancers diagnosed between 2001 and 2017. Alcohol-associated cancers, HPV-associated, obesity-associated, physical inactivity-associated, and tobacco-associated were defined using ICD-O-3 site codes. SEER*Stat 8.3.8 and Joinpoint regression program 4.8.0.1 were used to calculate the trends of associated cancers expressed per 100,000. Results: In 2017 the incidence of cancers in women associated with alcohol, smoking and obesity were 168/100,000, 134/100,000 and 121/100,000 respectively. Based on analysis of trends of women from 2001 to 2017, alcohol, smoking and physical inactivity related cancers decreased with an annual percent change (APC -0.51%, -0.96%, -0.92% respectively, p &lt; 0.001). However, there was no significant change in obesity, HPV, or post menopausal female breast cancer related cancers (APC: 0.07%, 0.09%, -0.08% respectively, p = 0.303, 0.181, 0.569). Based on age, in women less than 65, rates of obesity related cancers are increasing. Based on racial groups, all rates of cancer associated with modifiable factors are decreasing, however Hispanic women have an increasing rate of obesity related cancers (APC 0.46%, p &lt; 0.001). When examining differences in region, all rates of cancer are decreasing or unchanged except the south has an increasing rate of obesity related cancer (APC 0.28%, p &lt; 0.001). Using a projection model, obesity will become the highest incidence cancer in Hispanic women by 2035, surpassing alcohol and tobacco. In 2017 the incidence of cancers in men associated with tobacco, obesity, and alcohol were 209/100,000, 111/100,000 and 81/100,000 respectively. Based on analysis of trends in men alcohol, smoking, physical inactivity and obesity related cancers decreased (APC -1.42%, -1.59%, -3.15%, -0.41% respectively, p &lt; 0.001). HPV related cancers have increased (APC 2.36%, p &lt; 0.001). In men less than 60 years old, the rates of obesity related cancers are increasing. Using a prediction model, obesity is predicted to surpass tobacco as the most common social cause of cancer in 2020 for men 35-39, 2024 in men 40-44 and in 2030 in men 45-49. Conclusions: In women, most modifiable factors associated with cancer are decreasing except in obesity and HPV related cancers. In men, these rates of cancer are decreasing except HPV related cancers. However, rates of obesity related cancers are on the rise in Hispanic women and younger men. Obesity is set to become the major modifiable factor for many associated cancers.
Efficacy of platinum-based chemotherapy in advanced triple-negative breast cancer in association with homologous recombination deficiency.
Authors: Yimeng Chen, Lina Cui, Bei Zhang, Xiaochen Zhao, Binghe Xu
Journal: Journal of Clinical Oncology (2021)

e13051 Background: Previous studies have identified that at least 50% of triple negative breast cancer (TNBC) harbor mutation characteristics of homologous recombination deficiency (HRD). Thus, more sophisticated research into comprehensive genomic profiling of HRD is urgently needed. Whereas BRCA1/2-deficient advanced TNBC patients are sensitive to treatment with platinum, it is not yet clear whether HRD status could predict platinum response. Methods: 3DMed-HRD algorithm was developed based on loss of heterozygosity score (LOH), telomeric allelic imbalance score (TAI) and large-scale state transition score (LST) as previously described. HRD status was defined as HRD positive (deleterious mutation in BRCA1/2 or HRD score ≥30) or HRD negative (no deleterious mutation in BRCA1/2 and HRD score &lt; 30). Tumor samples from 207 TNBC patients were analyzed by next-generation sequencing. Deleterious or suspected deleterious mutations were included for analysis. Among the overall cohort, 34 patients with advanced TNBC treated with chemotherapy were analyzed. Cox regression model was applied to evaluate the relationship between HRD status and clinical outcomes. Results: Deleterious BRCA1/2 mutations were detected in 22.2% (46/207) of TNBC patients as well as 54.6% (113/207) were defined as HRD positive. The most frequent mutations in HRD-positive patients were TP53 (93.5%), MYC (29.0%), PIK3R1 (22.6%), PTEN (22.6%) and MCL1 (19.4%), while TP53 (77.8%), MYC (29.6%), PIK3CA (18.5%), KMT2C (14.8%) and RIT1 (14.8%) enriched in HRD-negative patients. Mutations in DNA Damage Response (DDR), P53, Checkpoint and Receptor Tyrosine Kinase (RTK) pathways were most involved in HRD positive patients. In advanced TNBC cohort, 19 patients received platinum-based and 15 received platinum-free chemotherapy in the first-line treatment. The progression-free survival (PFS) of the platinum-based group was longer than that of the platinum-free group (media PFS 9.1 vs 2.2 months, HR 0.44, 95%CI, 0.20-0.94, P = 0.009). In HRD-positive patients, median PFS was significantly longer in platinum-based group (N = 6) than platinum-free group (N = 8) (media PFS 13.6 vs 1.9 months, HR 0.30, 95%CI, 0.09-0.95, P = 0.008). No significant difference in PFS between platinum-based and platinum-free group (p = 0.332) in patients with HRD-negative tumors. Patients with mutations in homologous recombination (HR) pathway had a worse PFS compared to wild-type in platinum-free group (1.4 vs 3.0 months, p = 0.050). Conclusions: Our findings illustrate the potential of HRD status as a marker to guide chemotherapy in advanced TNBC. In HRD positive patients, platinum-based chemotherapy might be a preferable regimen. Patients with mutations in HR pathway had a shorter PFS in platinum-free group. Prospective study with a larger sample-size is needed for further validation of our findings.
Stereotactic body radiation therapy (SBRT) versus conventionally fractionated external beam radiation therapy in unfavorable intermediate-risk prostate cancer: An inverse propensity matched analysis.
Authors: Neal Andruska, Benjamin Walker Fischer-Valuck, Temitope Agabalogun, Ruben Carmona, Randall Brenneman, Hiram Alberto Gay, Jeff M. Michalski, Brian Christopher Baumann
Journal: Journal of Clinical Oncology (2021)

e17054 Background: Conventionally fractionated radiotherapy (CFRT) or moderately hypofractionated radiotherapy (MFRT) ± short-course androgen deprivation therapy (ADT) is commonly employed for unfavorable intermediate-risk (UIR) prostate cancer. Stereotactic body radiation therapy (SBRT) has not been widely adopted, but may have radiobiologic advantages over more conventionally fractionated treatments. We hypothesized that radiotherapy dose-escalation with SBRT (35-40Gy in ≤5 fractions) is associated with improved overall survival (OS) relative to biologically equivalent doses of CFRT (72-86.4Gy in 1.8-2.0Gy/fraction) or MFRT (≥60Gy in 2.4-3.2Gy/fraction) ± ADT. Methods: The National Cancer Database (NCDB) was used to identify 28,028 men with UIR prostate cancer who received CFRT with (n = 12,872) or without ADT (n = 12,984), MFRT with (n = 251) or without ADT (n = 281), and SBRT with (n = 212) or without ADT (n = 1,428). SBRT+ADT patients were excluded due to low patient numbers. Inverse probability of treatment weighting was used to balance measured confounders. Unweighted- and weighted- multivariable analysis (MVA) using Cox regression was used to compare OS hazard ratios. Results: Relative to CFRT without ADT, CFRT+ADT (Hazard Ratio (HR): 0.92, [95% Confidence Interval: 0.87-0.97], P = .002) and SBRT without ADT (HR: 0.74 [0.61-0.89], P = .002) were both associated with improved OS on MVA. Relative to CFRT+ADT, SBRT without ADT correlated with improved OS on MVA (HR: 0.81 [0.67-0.99], P = .04). Weight-adjusted MVA demonstrated that SBRT (HR: 0.80 [0.65-0.98], P = .036) and ADT (HR: 0.91 [0.86-0.97], P = .002) correlated with improved OS. SBRT was not associated with improved OS relative to MFRT. Conclusions: Using inverse propensity treatment weighting, we adjusted for age, comorbidity score, and tumor factors, and observed a significant overall survival benefit in favor of administering dose-escalated SBRT over CFRT+ADT. To our knowledge, this is the first study to show that SBRT is associated with improved OS relative to CFRT for men with UIR prostate cancer. Together, this suggests that SBRT offers a cheaper and shorter course of therapy that mitigates COVID-19 exposure, which also is associated with improved OS relative to CFRT for UIR prostate cancer and may obviate the need for ADT in this population. While we await results from several ongoing clinical trials, we believe this study lends support to the use of SBRT in men with UIR prostate cancer.
Screening protocols to detect subclinical respiratory infections in PID: findings from a European survey
Authors: S. Jolles, S. Sanchez-Ramon, I Quinti, P. Soler-Palacin, C. Agostini, B. Florkin, L-J Couderc, N. Brodszki, A. Jones, H. Longhurst, K. Warnatz, Filomeen Haerynck, A. Matucci, E. de Vries
Journal: Allergy (2015)
Dynamic innate immune response determines susceptibility to SARS-CoV-2 infection and early replication kinetics
Authors: Nagarjuna R. Cheemarla, Timothy A. Watkins, Valia T. Mihaylova, Bao Wang, Dejian Zhao, Guilin Wang, Marie L. Landry, Ellen F. Foxman
Journal: The Journal of Experimental Medicine (2021)

Initial replication of SARS-CoV-2 in the upper respiratory tract is required to establish infection, and the replication level correlates with the likelihood of viral transmission. Here, we examined the role of host innate immune defenses in restricting early SARS-CoV-2 infection using transcriptomics and biomarker-based tracking in serial patient nasopharyngeal samples and experiments with airway epithelial organoids. SARS-CoV-2 initially replicated exponentially, with a doubling time of ∼6 h, and induced interferon-stimulated genes (ISGs) in the upper respiratory tract, which rose with viral replication and peaked just as viral load began to decline. Rhinovirus infection before SARS-CoV-2 exposure accelerated ISG responses and prevented SARS-CoV-2 replication. Conversely, blocking ISG induction during SARS-CoV-2 infection enhanced viral replication from a low infectious dose. These results show that the activity of ISG-mediated defenses at the time of SARS-CoV-2 exposure impacts infection progression and that the heterologous antiviral response induced by a different virus can protect against SARS-CoV-2.
A multicenter, randomized phase 1b/2 study of gemcitabine and cisplatin with or without CPI-613 as first-line therapy for patients with advanced unresectable biliary tract cancer (BilT-04).
Authors: Vaibhav Sahai, Amy E. Chang, Oxana V. Crysler, David Bing Zhen, Muhammad Shaalan Beg, Timothy S. Pardee, Sanjeev Luther, Kent A. Griffith, Mark Zalupski
Journal: Journal of Clinical Oncology (2021)

TPS4158 Background: Patients (pts) with advanced biliary tract cancers (BTC) have poor prognosis despite systemic chemotherapy. Gemcitabine and cisplatin is a standard first-line systemic therapy with an overall response rate (ORR) of 26% and a median overall survival of 11.7 months. This investigator-initiated, multi-institutional phase 1b/2 trial is designed to investigate the role of gemcitabine, cisplatin and CPI-613 in pts with advanced BTC. CPI-613 is a stable intermediate of a lipoate analog that inhibits pyruvate dehydrogenase and a-ketoglutarate dehydrogenase enzymes of the tricarboxylic (TCA) cycle preferentially within the mitochondria of cancer cells. Methods: Key eligibility criteria include histologically confirmed, metastatic or unresectable BTC (intra- or extra-hepatic and gallbladder) without prior systemic treatment, measurable disease per RECIST v1.1, and ECOG PS 0-1. Primary objective of the phase 1b portion (n = 20 pts; TiTE-CRM methodology) is to determine the recommended phase 2 dose of the combination, and for the phase 2 portion, ORR (n = 48-58 pts; 2:1 randomization). Assuming a null hypothesis ORR of 25% and an alternative hypothesis of 43%, this ongoing trial has at least 80% power with a one-sided alpha of 0.05 to identify treatment efficacy of the study arm. Secondary objectives include evaluation of progression-free survival, overall survival, and safety in this patient population. Exploratory objectives include identification of molecular markers of response and resistance in tumor samples and serially collected blood (pre-, on-, and post-therapy), including whole exome/transcriptomic analysis, and immunohistochemical staining (PDK, PDH, KGDH, SOD2 and CD79a). Gemcitabine 1000 mg/m 2 , cisplatin 25 mg/m 2 with or without CPI-613 (dose levels: 500 mg/m 2 , 1000 mg/m 2 , 1500 mg/m 2 , and 2000 mg/m 2 ) will be given IV on days 1 and 8 every 21 days. In the absence of disease progression, pts may continue therapy for up to 2 years. Total accrual goal is 68-78 evaluable pts. To date, 5 of planned 20 pts enrolled on the phase 1b portion are without dose limiting toxicity. Clinical trial information: NCT04203160.