bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune Checkpoint Inhibitors (ICI) Enhance Cancer Associated Thrombosis (CAT) in Murine Model of Colon Carcinoma
Authors: Swaidani Shadi , Jun Shim Young , Rayman Patricia , Pavicic Paul G. , Diaz-Montero C. Marcela , Khorana Alok A , McCrae Keith R. 
Published: November 2021

Abstract
Abstract
Background:
Venous thromboembolism (VTE) is an important immune-related adverse event (irAE) associated with immune checkpoint inhibitors (ICI) cancer therapy. To better understand the pathogenesis of ICI-induced VTE during ICI treatment, we utilized a murine model of cancer associated thrombosis (CAT) to examine the impact of ICI treatment on the development of flow restriction-induced thrombosis.
Methods
A syngeneic colon carcinoma murine model (CT26) on BALB/c background was utilized to evaluate venous thrombosis following inferior vena cava (IVC) ligation. Non-tumor-bearing and tumor-bearing animals were treated with therapeutic doses of ICI: anti-programmed cell death receptor 1 antibody (anti-PD1) and cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4) or isotype control antibodies. Mice underwent surgical treatment for IVC ligation followed by surgical retrieval of thrombus. Western blot analysis was performed on plasma cleaved high molecular weight kininogen (cHK), and citrullinated histone H3 (CitH3).
Results
Tumor-bearing mice undergoing IVC ligation after anti-PD1 and anti-CTLA4 infusion developed larger thrombi compared to mice treated with isotype control IgG. Thrombus weights in CT26 tumor-bearing mice treated with ICI (19.56±4.41 mg) were significantly increased compared to those in mice treated with isotype control IgG (14.67±2.76 mg) (P=0.043). The weight of thrombi in non-tumor-bearing mice was not affected by ICI treatment (9.25±2.22 mg with control IgG vs 9.33±1.15 mg with ICI). In addition, there was a significant increase in thrombus length in mice treated with ICI (9±1.02 mm vs 7.61±0.99 mm with IgG, P=0.039). Cleaved high molecular weight kininogen (cHK), an indicator of contact activation was increased in plasma pre-IVC occlusion from ICI-treated mice compared to IgG-treated mice (68% vs 38% in HK cleavage). Citrullinated histone H3 (CitH3), a NETosis marker, was elevated in plasma (and in thrombus) post-IVC occlusion from ICI-treated mice compared to that of IgG-treated mice.
Conclusions
ICI treatment of tumor-bearing mice undergoing flow restriction-induced thrombosis resulted in enhanced clot formation. Larger thrombi in ICI treated mice was accompanied with enhanced contact activation and NETosis marker CitH3.
Figure 1 Figure 1.

Disclosures
Khorana: Halozyme: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Anthos: Consultancy, Honoraria. McCrae: Dova, Novartis, Rigel, and Sanofi Genzyme: Consultancy; Sanofi, Novartis, Alexion, and Johnson & Johnson: Consultancy, Honoraria.
Reduced-Dose Ibrutinib Is Well Tolerated and Cost Effective for the Treatment of Chronic Lymphocytic Leukemia in Frail Older Adults
Authors: Chhina Arashpreet , Marin Monica Pernia , Thomas Shrina P , Vallejo Elizabeth G , Cappell Kathryn , Jain Maneesh 
Published: November 2021

Abstract
Ibrutinib is an inhibitor of Bruton's tyrosine kinase (BTK) that is used for the treatment of multiple hematologic malignancies including chronic lymphocytic leukemia (CLL) with promising outcomes. Its use has been associated with significant side effects including diarrhea, fatigue, infections, arthralgias, hemorrhage, and atrial fibrillation among others. Ibrutinib-associated adverse events have led to its discontinuation in more than one-fifth of CLL patients treated. Specifically, in the real-world setting, 21% to 30% of patients have needed an Ibrutinib dose interruption or reduction. Moreover, the associated toxicity seems to be more prominent in the geriatric population given the poor functional reserve, impaired mobility, and preexisting comorbidities. In the elderly, moderate to severe treatment-related toxicity often times leads to a higher number of hospitalizations, which ultimately increases the risk of complications and health care costs. Some studies have reported that Ibrutinib dose reductions have not had a significant impact on the progression-free-survival or overall survival in the general population. Nevertheless, there is not sufficient data or consent about the use of a reduced dose of Ibrutinib for treatment of CLL in frail older adults. In addition, annual costs of treatment with complete-dose Ibrutinib for veterans exceed $100,000. As it is common to reach complete remission with Ibrutinib monotherapy, patients will remain on therapy long-term, compounding financial impact over their treatment lifetime. Reduced dose Ibrutinib can lower total cost by 50% or more and thereby increase patient adherence due to decreased economic burden. Therefore, we present a retrospective review of a series of 7 cases involving frail older adults with CLL treated with Ibrutinib at the Washington DC Veterans Affairs Medical Center. Six out of seven patients received a reduced Ibrutinib dose and had a complete response whereas one patient received the dose recommended by the manufacturer leading to a prolonged hospital stay due to the adverse effects. We report the disease control evidenced by a decrease in white blood cell count, alleviation of "B symptoms", and resolution of lymphadenopathy along with side effects with an Ibrutinib dose ranging from 140 to 280 mg per day. We also report the cost benefits obtained with the use of a reduced Ibrutinib dose. We hope that sharing our experience encourages clinical trials aiming to determine the minimal dose needed to effectively treat CLL while limiting toxicity, decreasing health care costs, and preserving quality of life in frail older adults.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Clinical Characteristics and Survival of Non-Nasal Natural Killer/T-Cell Lymphoma from 2 Cancer Centers from Peru
Authors: Vasquez Jule F , Castro Melanie , Diaz Alonso , Barrionuevo Carlos , Samanez-Figari Cesar 
Published: November 2021

Abstract
Background
Natural killer/T-cell lymphoma (NKTCL) is an aggressive lymphoma with poor prognosis mainly seen in Asian and South American countries, most patients have nasal involvement. Non-nasal NKTCL have a dismal prognosis. However, data about this very specific population is mostly known in Asians but little known in Latin American (LATAM) population. Our aim is to describe the clinical characteristics and survival of newly diagnosed NKTCL patients in Peru
Methods: This is a retrospective study, including all patients with a pathological diagnosis of NKTCL patients &gt;13 years at the Instituto Nacional de Enfermedades Neoplasicas (INEN) and Oncosalud between 2002 and 2019. The estimate of the survival curves was performed by the Kaplan-Meier method, and the difference was computed by the log-rank test.
Results: 60 patients were included for the analysis. The median age was 37 years (range 15-83). 62% were male, 51% had B-symptoms, 56% had stage III/IV disease, 54% had elevated serum LDH, 29% had nodal involvement. The most frequent non-nasal sites were oropharynx, soft tissue, cutaneous, gastrointestinal and orbit with 24%, 17%, 12%, 7% and 5%, respectively. 79% patients received systemic chemotherapy, 7% received radiotherapy alone and 14% did not received chemotherapy because poor performance status. Of patients who received chemotherapy only 20% received a L-asparaginase-based chemotherapy. The median follow-up time was 8 months (1-103). The median overall survival (OS) was 14 months (interquartile range [IQR] 4-29), 1y OS was 51% (95% CI 33-67), 3y OS 21% (95% CI 7-40), 5y OS 14% (95% CI 3-34), figure 1. The median overall survival according to LDH level was 10 months regardless of the levels (p=0.84), figure 2. The median OS for female and male were 8 and 10 months, respectively p=0.59)
Conclusions: Peruvian patients with non-nasal NKTCL are younger, with presence of B-symptoms, advance stage and elevated LDH levels compared to those reported in nasal NKTCL. The most frequent non nasal NKTCL is located on the oropharynx. OS of non-nasal NKTCL is extremely poor. Elevated LDH and sex are not prognostic factors for OS. A larger cohort and follow-up are needed to evaluate prognostic factors in this population.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Leaf functional traits differentiation in relation to covering materials of urban tree pits
Authors: Zhu Jiyou , Cao Yujuan , He Weijun , Xu Qing , Xu Chengyang , Zhang Xinna 
Published: November 2021

AbstractBackgroundUnderstanding the ecological strategies of urban trees to the urban environment is crucial to the selection and management of urban trees. However, it is still unclear whether urban tree pit cover will affect plant functional traits. Here, we study the response of urban trees to different tree pit covers, analyzed the effects of different cover types on soil properties and their trade-off strategies based on leaf functional traits.ResultsWe found that there were obvious differences in the physical properties of the soil in different tree pit covers. Under the different tree pit cover types, soil bulk density and soil porosity reached the maximum under cement cover and turf cover, respectively. We found that tree pit cover significantly affected the leaf properties of urban trees. Leaf thickness, chlorophyll content index and stomatal density were mainly affected by soil bulk density and non-capillary porosity in a positive direction, and were affected by soil total porosity and capillary porosity in a negative direction. Leaf dry matter content and stomata area were mainly negatively affected by soil bulk density and non-capillary porosity, and positively affected by soil total porosity and capillary porosity. Covering materials of tree pits promoted the functional adjustment of plants and form the best combination of functions.ConclusionUnder the influence of tree pit cover, plant have low specific leaf area, stomata density, high leaf thickness, chlorophyll content index, leaf dry matter content, leaf tissue density and stomata area, which belong to “quick investment-return” type in the leaf economics spectrum.
Association between enterocyte injury and fluid balance in patients with septic shock: a post hoc exploratory analysis of a prospective observational study
Authors: Yokoyama Haruka , Sekino Motohiro , Funaoka Hiroyuki , Sato Shuntaro , Araki Hiroshi , Egashira Takashi , Yano Rintaro , Matsumoto Sojiro , Ichinomiya Taiga , Higashijima Ushio , Hara Tetsuya 
Published: November 2021

Abstract
Background
The required fluid volume differs among patients with septic shock. Enterocyte injury caused by shock may increase the need for fluid by triggering a systematic inflammatory response or an ischemia-reperfusion injury in the presence of intestinal ischemia/necrosis. This study aimed to evaluate the association between enterocyte injury and positive fluid balance in patients with septic shock.

Methods
This study was a post hoc exploratory analysis of a prospective observational study that assessed the association between serum intestinal fatty acid-binding protein, a biomarker of enterocyte injury, and mortality in patients with septic shock. Intestinal fatty acid-binding protein levels were recorded on intensive care unit admission, and fluid balance was monitored from intensive care unit admission to Day 7. The association between intestinal fatty acid-binding protein levels at admission and the infusion balance during the early period after intensive care unit admission was evaluated. Multiple linear regression analysis, with adjustments for severity score and renal function, was performed.

Results
Overall, data of 57 patients were analyzed. Logarithmically transformed intestinal fatty acid-binding protein levels were significantly associated with cumulative fluid balance per body weight at 24 and 72 h post-intensive care unit admission both before (Pearson’s r = 0.490 [95% confidence interval: 0.263–0.666]; P < 0.001 and r = 0.479 [95% confidence interval: 0.240–0.664]; P < 0.001, respectively) and after (estimate, 14.4 [95% confidence interval: 4.1–24.7]; P = 0.007 and estimate, 26.9 [95% confidence interval: 11.0–42.7]; P = 0.001, respectively) adjusting for severity score and renal function.

Conclusions
Enterocyte injury was significantly associated with cumulative fluid balance at 24 and 72 h post-intensive care unit admission. Enterocyte injury in patients with septic shock may be related to excessive fluid accumulation during the early period after intensive care unit admission.
The effect of menopausal hormone therapy on gastrointestinal cancer risk and mortality in South Korea: a population-based cohort study
Authors: Nam Ji Hyung , Jang Sung-In , Park Hyun Soo , Kim Jae Hak , Lee Jun Kyu , Lim Yun Jeong , Koh Moon-Soo , Lee Jin Ho , Park Sohee , Nam Chung Mo , Park Eun-Cheol 
Published: November 2021

Abstract
Background
The effect of menopausal hormone therapy (MHT) on gastrointestinal (GI) cancers is controversial, and no research has been conducted in the East. This study investigates the association between MHT and GI cancer risks in South Korea.

Methods
A prescription-based cohort study was conducted using the NHIS Sample Cohort (2002–2013) of Korea. We used 1:5 propensity score matching, and 22,577 MHT users and 111,113 non-users were selected. Kaplan–Meier survival curves with log-rank tests were used. Cox proportional hazard models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Landmark analysis was used to determine dose–response relationship.

Results
The median follow-up was 79.6 of months. Kaplan–Meier survival curve showed less frequent GI cancer diagnoses in MHT users compared to non-users (0.13 vs. 0.16 per 100,000 person-years). Menopausal hormone therapy was associated with decreased incidence of GI cancer (HR = 0.809, 95%CI = 0.691–0.946) and colorectal cancer (CRC) (HR = 0.757, 95%CI = 0.577–0.995). Gastric cancer (GC) incidence showed marginal significance (HR = 0.787, 95%CI = 0.605–1.023). The mortality from GI cancer was lower in MHT users than in non-users (HR = 0.737, 95%CI = 0.547–0.993). The relationship between MHT and GI cancer was stronger with increasing MHT dose in terms of both incidence (Ptrend = 0.0002) and mortality (Ptrend = 0.0064).

Conclusions
The association between MHT use and reduced risks of GI cancers was attributed to CRC and GC and showed a dose–response relationship in a population-based cohort study.
Physical capacity, subjective health, and life satisfaction in older women: a 10-year follow-up study
Authors: Qazi Sarang Latif , Koivumaa-Honkanen Heli , Rikkonen Toni , Sund Reijo , Kröger Heikki , Isanejad Masoud , Sirola Joonas 
Published: November 2021

Abstract
Background
Physical capacity and subjective wellbeing are important for healthy aging. Our aim was to study how objective/subjective physical capacity and subjective health relate to life satisfaction, in a 10-year follow-up of aging women.

Methods
The participants (n = 1485, mean age 67.4 years) consisted of community-dwelling older women living in Kuopio, Finland. Grip strength and one-legged stance test time were used as objective, and self-rated mobility (SRM) as subjective physical capacity measures. Self-rated health (SRH) and SRM were assessed with one-item scales and life satisfaction with a 4-item scale. Correlation and linear regression were used to analyze these relationships and correlation network analysis to visualize them. Age and BMI were included in the analysis as adjusting factors.

Results
All the study variables were significantly correlated with baseline and follow-up life satisfaction, except BMI, which was only associated with life satisfaction at follow-up. On both occasions, SRH and SRM were the two strongest correlates of life satisfaction, but their mutual correlation was still higher. In linear regression analyses, SRH was positively associated with both baseline and follow-up life satisfaction, but physical capacity measures became non-significant after including SRH and SRM in the model. In the partial correlation network analyses, SRH and SRM were the most central nodes, connecting every other variable.

Conclusions
Self-reports on health, mobility, and life satisfaction are closely intertwined and provide easily accessible health information among aging women, but the impacts of objective physical capacity measures warrant further longitudinal studies in respect to subjective wellbeing among aging people.
The prognostic role of heart rate recovery after exercise and metabolic syndrome in IgA nephropathy
Authors: Sági Balázs , Késői István , Vas Tibor , Csiky Botond , Nagy Judit , Kovács Tibor 
Published: November 2021

Abstract
Background
Cardiovascular (CV) morbidity and mortality are higher in chronic kidney disease (CKD) than in the general population. Reduced heart rate recovery (HRR) is an independent risk factor for CV disease. The aim of the study was to determine the prognostic role of HRR in a homogenous group of CKD patients.

Methods
One hundred and twenty-five IgA nephropathy patients (82 male, 43 female, age 54.7 ± 13 years) with CKD stage 1–4 were investigated and followed for average 70 months. We performed a graded exercise treadmill stress test. HRR was derived from the difference of the peak heart rate and the heart rate at 1 min after exercise. Patients were divided into two groups by the mean HRR value (22.9 beats/min). The composite (CV and renal) endpoints included all-cause mortality and any CV event such as stroke, myocardial infarction, revascularisation (CV) and end-stage renal disease, renal replacement therapy (renal).

Results
Patients with reduced HRR (< 23 bpm) had significantly more end point events (22/62 patients vs. 9/53 patients, p = 0.013) compared to the higher HRR (≥23 bpm). Of the secondary the endpoints (CV or renal separately) rate of the renal endpoint was significantly higher in the lower HRR group (p = 0.029), while there was no significant difference in the CV endpoint between the two HRR groups (p = 0.285). Independent predictors of survival were eGFR and diabetes mellitus by using Cox regression analysis. Kaplan-Meier curves showed significant differences in metabolic syndrome and non-metabolic syndrome when examined at the combined endpoints (cardiovascular and renal) or at each endpoint separately. The primary endpoint rate was increased significantly with the increased number of metabolic syndrome component (Met.sy. comp. 0 vs. Met. sy. comp. 2+, primary endpoints, p = 0.012).

Conclusion
Our results showed that reduced HRR measured by treadmill exercise test has a predictive value for the prognosis of IgA nephropathy. The presence of metabolic syndrome may worsen the prognosis of IgA nephropathy.
Safety and efficacy of interleukin-6-receptor inhibitors in the treatment of neuromyelitis optica spectrum disorders: a meta-analysis
Authors: Kharel Sanjeev , Shrestha Suraj , Ojha Rajeev , Guragain Neha , Ghimire Rakesh 
Published: November 2021

Abstract
Background
Interleukin-6-receptor inhibitors like Tocilizumab and Satralizumab are showing promising results in the treatment of Neuromyelitis Optica spectrum disorder (NMOSD). We aimed to investigate the efficacy and safety of various Interleukin-6-receptor inhibitors in the management of NMO/NMOSD.

Methods
PubMed, Embase, and The Cochrane Library were systematically searched for suitable studies. Change in Annualized Relapse Ratio (ARR), Change in Extended Disability Status Scale (EDSS) s, the proportion of relapse-free patients and proportion of patients with adverse events, including serious adverse events and mortality were the parameters considered for the meta-analysis for Tocilizumab. Mean difference (MD) with 95% CI was used to quantify the change in ARR and change in EDSS before and after treatment. A forest plot was prepared to indicate the efficacy and adverse effects outcomes. The results were compared with those of Satralizumab included in two trials.

Results
A total of nine studies with 202 patients were included in our study. Tocilizumab found a good proportion (76.95% CI: 0.61–0.91; p < 0.001) of relapse free patients at follow up. It also significantly reduced mean ARR (mean difference: -2.6, 95% CI: − 2.71 to − 1.68; p < 0.001) and but did not show significant difference in change in EDSS score (mean difference = − 0.79, 95% CI: − 1.89 to − 0.31; p = 0.16). Also, the toxicity profile of Tocilizumab was acceptable considering the proportions of patients with adverse events 56% (95% C.I.;0.27–0.85, I2 = 88.95%, p < 0.001), proportions of patients with serious adverse events 11% (95% C.I.; 0.05 to 0.17, I2 = 0%, p < 0.001) and zero treatment related deaths. SAkura studies for Satralizumab showed similar relapse free patients (70% to 80%) and reduction of ARR and EDSS from baseline. Some studies of Tocilizumab have shown to reduce pain and fatigue while trials of Satralizumab had non-significant findings.

Conclusion
Interleukin-6-receptor inhibitors therapy showed a promising result with good efficacy and acceptable adverse events profile for treatment of NMOSD.
Immune checkpoint inhibitors plus neoadjuvant chemotherapy in early triple-negative breast cancer: a systematic review and meta-analysis
Authors: Xin Yuanfang , Shen Guoshuang , Zheng Yonghui , Guan Yumei , Huo Xingfa , Li Jinming , Ren Dengfeng , Zhao Fuxing , Liu Zhen , Li Zitao , Zhao Jiuda 
Published: November 2021

Abstract
Purpose
Some studies have shown that Immune checkpoint inhibitors (ICIs) have a favorable efficacy in advanced triple negative breast cancer (TNBC) patients, but the results are controversial in neoadjuvant chemotherapy (NACT) stage. The purpose of this study is to evaluate the efficacy and safety after NACT plus ICIs in early TNBC patients.

Methods
After searching PubMed, EMBASE, the Cochrane library and several mainly oncology conferences up to 30 January 2021 systematically, and define randomized controlled trials (RCTs) exploring the efficacy and safety of programmed death protein-1/programmed cell death-Ligand 1(PD-1/PD-L1) inhibitors plus neoadjuvant chemotherapy in TNBC patients. The primary endpoint was the pathological complete response (pCR) in intention-to-treat populations (ITT), and the secondary endpoints were event-free survival (EFS) and safety analysis in the ITT populations.

Results
Six RCTs (N = 2142) were included in our meta-analysis; NACT plus ICIs increased pCR rates compared with NACT in intention-to-treat (ITT) populations (OR: 1.91; 95% CI: 1.32–2.78, P < 0.001). The pCR rate also increased in both PD-L1 positive (OR: 1.65; 95% CI: 1.26–2.16, P < 0.001) and PD-L1 negative patients (OR: 1.56; 95% CI: 1.04–2.33, P = 0.03), especially in PD-L1 positive patients. The benefit was also observed in nodal-positive populations (OR: 2.52; 95% CI: 1.69–3.77, P < 0.001) and Eastern Cooperative Oncology Group performance-status score (ECOG PS) 0 subgroup (OR: 1.90; 95% CI: 1.42–2.53, P < 0.001). Three RCTs (N = 1615) reported EFS and the results showed that adding PD-1/PD-L1 inhibitors increased EFS (HR 0.65, 95% CI 0.50–0.83, P = 0.0007) in ITT populations with a short follow-up time. In the safety analysis of 2205 patients with early TNBC from five eligible studies, NACT plus ICIs had a higher risk of grade 3–4 diarrhea (OR: 2.54; 95% CI: 1.21–5.32; P = 0.01), any grade of adverse effects(AEs)including vomiting (OR: 1.37; 95% CI: 1.00–1.86; P = 0.05), hyperthyroidism (OR: 6.04; 95% CI: 2.39–15.29; P < 0.001), and hypothyroidism (OR: 5.04; 95% CI: 3.02–8.39; P < 0.001).

Conclusions
PD-1/PD-L1 inhibitors combined with chemotherapy can improve pCR rates and EFS, and with an increased incidence of some immune-related AEs compared with chemotherapy alone. NACT plus ICIs might be an option in patients with in PD-L1 positive and high-risk populations with positive nodal disease early TNBC.