bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new role for circulating T follicular helper cells in humoral response to anti-PD-1 therapy
Authors: Sánchez-Alonso Santiago , Setti-Jerez Giulia , Arroyo Montserrat , Hernández Tathiana , Martos Mª Inmaculada , Sánchez-Torres Jose Miguel , Colomer Ramon , Ramiro Almudena R , Alfranca Arantzazu 
Published: September 2020

BackgroundLung cancer is one of the most frequent malignancies in humans and is a major cause of death. A number of therapies aimed at reinforcing antitumor immune response, including antiprogrammed cell death protein 1 (anti-PD-1) antibodies, are successfully used to treat several neoplasias as non-small cell lung cancer (NSCLC). However, host immune mechanisms that participate in response to anti-PD-1 therapy are not completely understood.MethodsWe used a syngeneic immunocompetent mouse model of NSCLC to analyze host immune response to anti-PD-1 treatment in secondary lymphoid organs, peripheral blood and tumors, by flow cytometry, immunohistochemistry and quantitative real-time PCR (qRT-PCR). In addition, we also studied specific characteristics of selected immune subpopulations in ex vivo functional assays.ResultsWe show that anti-PD-1 therapy induces a population of circulating T follicular helper cells (cTfh) with enhanced B activation capacity, which participates in tumor response to treatment. Anti-PD-1 increases the number of tertiary lymphoid structures (TLS), which correlates with impaired tumor growth. Of note, TLS support cTfh-associated local antibody production, which participates in host immune response against tumor.ConclusionThese findings unveil a novel mechanism of action for anti-PD-1 therapy and provide new targets for optimization of current therapies against lung cancer.
Derivo embolization device in the treatment of unruptured intracranial aneurysms: a prospective multicenter study
Authors: Taschner Christian A , Stracke Christian Paul , Dorn Franziska , Kadziolka Krzysztof Bartosz , Kreiser Kornelia , Solymosi László , Pham Mirko , Buhk Jan Hendrik , Turowski Bernd , Reith Wolfgang , Elsheikh Samer , Meckel Stephan , Janssen Hendrik , Hammer Alexander , Beuing Oliver , Jansen Olav , Urbach Horst , Knauth Michael , Jenkner Carolin , Chapot René 
Published: September 2020

Background
Flow diverters (FD) are used regularly for the endovascular treatment of unruptured intracranial aneurysms. We aimed to assess the safety and effectiveness of the Derivo embolization device (DED) with respect to long-term clinical and angiographic outcomes.

Methods
A prospective multicenter trial was conducted at 12 centers. Patients presenting with modified Rankin Score (mRS) of 0–1, treated for unruptured intracranial aneurysms with DED were eligible. Primary endpoint was the mRS assessed at 18 months with major morbidity defined as mRS 3–5. Satisfactory angiographic occlusion was defined as 3+4 on the Kamran scale.

Results
Between July 2014 and February 2018, 119 patients were enrolled. Twenty-three patients were excluded. Ninety-six patients, 71 (74%) female, mean age 54±12.0 years, were included in the analysis. Mean aneurysm size was 14.2±16.9 mm. The mean number of devices implanted per patient was 1.2 (range 1–3). Clinical follow-up at 18 months was available in 90 (94%) patients, resulting in a mean follow-up period of 14.8±5.2 months. At last available follow-up of 96 enrolled patients, 91 (95%) remained mRS 0–1. The major morbidity rate (mRS 3–5) was 3.1% (3/96), major stroke rate was 4.2% (4/96), and mortality was 0%. Follow-up angiographies were available in 89 (93%) patients at a median of 12.4±5.84 months with a core laboratory adjudicated satisfactory aneurysm occlusion in 89% (79/89).

Conclusion
Our results suggest that DED is a safe and effective treatment for unruptured aneurysms with high rates of satisfactory occlusion and comparably low rates of permanent neurological morbidity and mortality.

Trial registration
DRKS00006103
The transvenous retrograde pressure cooker technique for the curative embolization of high-grade brain arteriovenous malformations
Authors: Koyanagi Masaomi , Mosimann Pascal John , Nordmeyer Hannes , Heddier Markus , Krause Juergen , Narata Ana-Paula , Serwi Ahmed El , Stracke Christian Paul , Chapot René 
Published: September 2020

BackgroundTransvenous embolization of brain arteriovenous malformations (AVMs) can be curative. We aimed to evaluate the cure rate and safety of the transvenous retrograde pressure cooker technique (RPCT) using coils and n-butyl-2-cyanoacrylate as a venous plug.MethodsAll AVM patients treated via transvenous embolization between December 2004 and February 2017 in a single center were extracted from our database. Inclusion criteria were: inability to achieve transarterial cure alone; AVM < 3 cm; and single main draining vein. Outcome measures were immediate and 90 days' angiographic AVM occlusion rate, and morbidity and mortality at 30 days and 12 months, according to the modified Rankin Scale (mRS) score.ResultsFifty-one patients (20 women; median age 47 years) were included. A majority (71%) were high grade (3 to 5 in the Spetzler–Martin classification). AVMs were deeply seated in 30 (59%) and cortical in 21 patients (41%). Thirty-three patients were previously embolized transarterially (65%). All patients but one were cured within a single session with the RPCT (96%). Cure was confirmed on follow-up digital subtraction angiography at 3 months in 82% of patients. Three patients experienced intracranial hemorrhage (6%), one requiring surgical evacuation. There were no deaths. One treatment-related major permanent deficit was observed (2.0%). Mean mRS before treatment, at 30 days, and 12 months after RPCT was 1.5, 1.5, and 1.3, respectively.ConclusionsThe retrograde pressure cooker technique can be curative in carefully selected high-grade AVMs. Long-term follow-up and prospective studies are needed to confirm our results.
Snare salvage technique for deformed WEB device after deployment
Authors: Aljuboori Zaid , Ding Dale , James Robert F 
Published: September 2020

The Woven EndoBridge (WEB) device is a new endovascular technology that allows safe and effective treatment of wide-neck bifurcation aneurysms without the need for dual antiplatelet therapy.1–4 The case is presented of a patient in their 50 s with a history of systemic lupus erythematosus and receiving warfarin for recurrent deep venous thrombosis and an unruptured right middle cerebral artery bifurcation aneurysm. The aneurysm was treated with a WEB SL aneurysm embolization device (MicroVention, Tustin, California, USA). After the final deployment, a technical error (inadvertent forward movement of the pusher) led to the deformation of the device along its longitudinal axis, leaving the aneurysm partially untreated. An Amplatz Goose Neck Microsnare was used to capture the proximal detachment marker and used gentle traction to restore the original shape of the device (video 1).5–7 A follow-up angiogram revealed a restoration of the device’s shape with a similar result during the 4- month follow-up angiogram.Video 1
Experimental and theoretical studies on luminescent mechanisms and different visual color of the mixed system composed of MgGeO3:Mn, Eu and Zn2GeO4:Mn
Authors: Xia Chuanhui , Zhou Mu , He Miao , Yang Liu , Liu Miao , Zhou Ping , Chen Hang , Wang Feng 
Published: September 2020

In this work, the mixed system composed of Zn2GeO4: Mn and MgGeO3: Mn, Eu was synthesized by the high temperature solid phase method. Under the external excitation, visual color of samples was yellow. However, after the excitation was completed, visual color turned to be red. From luminescence spectrum, it was found that Zn2GeO4: Mn emitted green fluorescence of 534 nm under the excitation of 375 nm light. At the same time, MgGeO3: Mn, Eu emitted both fluorescence and persistent luminescence (PersL) of 668 nm. Moreover, the properties of PersL present samples were superior to other red PersL materials. Fine band structures from density functional theory (DFT) indicated that there were different luminescent mechanisms of Zn2GeO4: Mn and MgGeO3: Mn, Eu. When Zn2GeO4: Mn was excited, electron transitioned from VB to CB directly. Through CB, the electron was captured by the4T2(D) of Mn ion, then the electron jumped from4T2(D) to VB and recombined at once with the previous hole and emitted a 534 nm photon. When MgGeO3: Mn, Eu was excited, electron transitioned from6A1(S) of Mn ion to CB and left a hole. Through CB, electron was captured by7F6levels of Eu[Formula: see text] and remained metastable for a long time, which slowed down the recombined rate between electron and hole. Under thermal stimulation, the captured electron returned to CB from7F6levels and was recaptured by the4T2(D) of Mn. The electron transitioned down toward6A1(S) and recombined with the hole immediately, then emitted a photon with 668 nm.
Visualization of Activated T Cells by OX40-ImmunoPET as a Strategy for Diagnosis of Acute Graft-versus-Host Disease
Authors: Alam Israt S. , Simonetta Federico , Scheller Lukas , Mayer Aaron T. , Murty Surya , Vermesh Ophir , Nobashi Tomomi W. , Lohmeyer Juliane K. , Hirai Toshihito , Baker Jeanette , Lau Kenneth H. , Negrin Robert , Gambhir Sanjiv S. 
Published: September 2020

Abstract

Graft-versus-host disease (GvHD) is a major complication of allogeneic hematopoietic cell transplantation (HCT), mediated primarily by donor T cells that become activated and attack host tissues. Noninvasive strategies detecting T-cell activation would allow for early diagnosis and possibly more effective management of HCT recipients. PET imaging is a sensitive and clinically relevant modality ideal for GvHD diagnosis, and there is a strong rationale for the use of PET tracers that can monitor T-cell activation and expansion with high specificity. The TNF receptor superfamily member OX40 (CD134) is a cell surface marker that is highly specific for activated T cells, is upregulated during GvHD, and mediates disease pathogenesis. We recently reported the development of an antibody-based activated T-cell imaging agent targeting OX40. In the present study, we visualize the dynamics of OX40 expression in an MHC-mismatch mouse model of acute GvHD using OX40-immunoPET. This approach enabled visualization of T-cell activation at early stages of disease, prior to overt clinical symptoms with high sensitivity and specificity. This study highlights the potential utility of the OX40 PET imaging as a new strategy for GvHD diagnosis and therapy monitoring.

Significance:
OX40-immunoPET imaging is a promising noninvasive strategy for early detection of GvHD, capable of detecting signs of GvHD pathology even prior to the development of overt clinical symptoms.
Multimodal CEA-Targeted Image-Guided Colorectal Cancer Surgery using 111In-Labeled SGM-101
Authors: de Gooyer Jan Marie , Elekonawo Fortuné M.K. , Bos Desirée L. , van der Post Rachel S. , Pèlegrin André , Framery Bérénice , Cailler Françoise , Vahrmeijer Alexander L. , de Wilt Johannes H.W. , Rijpkema Mark 
Published: September 2020

Abstract

Purpose:
Intraoperative image guidance may aid in clinical decision-making during surgical treatment of colorectal cancer. We developed the dual-labeled carcinoembryonic antigen–targeting tracer, [111In]In-DTPA-SGM-101, for pre- and intraoperative imaging of colorectal cancer. Subsequently, we investigated the tracer in preclinical biodistribution and multimodal image-guided surgery studies, and assessed the clinical feasibility on patient-derived colorectal cancer samples, paving the way for rapid clinical translation.

Experimental Design:
SGM-101 was conjugated with p-isothiocyanatobenzyl–diethylenetriaminepentaacetic acid (DTPA) and labeled with Indium-111 (111In). The biodistribution of 3, 10, 30, and 100 μg [111In]In-DTPA-SGM-101 was assessed in a dose escalation study in BALB/c nude mice with subcutaneous LS174T human colonic tumors, followed by a study to determine the optimal timepoint for imaging. Mice with intraperitoneal LS174T tumors underwent micro-SPECT/CT imaging and fluorescence image–guided resection. In a final translational experiment, we incubated freshly resected human tumor specimens with the tracer and assessed the tumor-to-adjacent tissue ratio of both signals.

Results:
The optimal protein dose of  [111In]In-DTPA-SGM-101 was 30 μg (tumor-to-blood ratio, 5.8 ± 1.1) and the optimal timepoint for imaging was 72 hours after injection (tumor-to-blood ratio, 5.1 ± 1.0). In mice with intraperitoneal tumors, [111In]In-DTPA-SGM-101 enabled preoperative SPECT/CT imaging and fluorescence image–guided resection. After incubation of human tumor samples, overall fluorescence and radiosignal intensities were higher in tumor areas compared with adjacent nontumor tissue (P &lt; 0.001).

Conclusions:
[111In]In-DTPA-SGM-101 showed specific accumulation in colorectal tumors, and enabled micro-SPECT/CT imaging and fluorescence image–guided tumor resection. Thus, [111In]In-DTPA-SGM-101 could be a valuable tool for preoperative SPECT/CT imaging and intraoperative radio-guided localization and fluorescence image–guided resection of colorectal cancer.
Pulmonary Vein Isolation With Single Pulse Irreversible Electroporation
Authors: Loh Peter , van Es René , Groen Marijn H.A. , Neven Kars , Kassenberg Wil , Wittkampf Fred H.M. , Doevendans Pieter A. 
Published: September 2020

Background:
Irreversible electroporation (IRE) is a promising new nonthermal ablation technology for pulmonary vein (PV) isolation in patients with atrial fibrillation. Experimental data suggest that IRE ablation produces large enough lesions without the risk of PV stenosis, artery, nerve, or esophageal damage. This study aimed to investigate the feasibility and safety of single pulse IRE PV isolation in patients with atrial fibrillation.

Methods:
Ten patients with symptomatic paroxysmal or persistent atrial fibrillation underwent single pulse IRE PV isolation under general anesthesia. Three-dimensional reconstruction and electroanatomical voltage mapping (EnSite Precision, Abbott) of left atrium and PVs were performed using a conventional circular mapping catheter. PV isolation was performed by delivering nonarcing, nonbarotraumatic 6 ms, 200 J direct current IRE applications via a custom nondeflectable 14-polar circular IRE ablation catheter with a variable hoop diameter (16–27 mm). A deflectable sheath (Agilis, Abbott) was used to maneuver the ablation catheter. A minimum of 2 IRE applications with slightly different catheter positions were delivered per vein to achieve circular tissue contact, even if PV potentials were abolished after the first application. Bidirectional PV isolation was confirmed with the circular mapping catheter and a post ablation voltage map. After a 30-minute waiting period, adenosine testing (30 mg) was used to reveal dormant PV conduction.

Results:
All 40 PVs could be successfully isolated with a mean of 2.4±0.4 IRE applications per PV. Mean delivered peak voltage and peak current were 2154±59 V and 33.9±1.6 A, respectively. No PV reconnections occurred during the waiting period and adenosine testing. No periprocedural complications were observed.

Conclusions:
In the 10 patients of this first-in-human study, acute bidirectional electrical PV isolation could be achieved safely by single pulse IRE ablation.
Power, Lesion Size Index and Oesophageal Temperature Alerts During Atrial Fibrillation Ablation
Authors: Leo Milena , Pedersen Michala , Rajappan Kim , Ginks Matthew R. , Hunter Ross J. , Bowers Robert , Kalla Manish , Bashir Yaver , Betts Timothy R. 
Published: September 2020

Background:
Low radiofrequency powers are commonly used on the posterior wall of the left atrium for atrial fibrillation ablation to prevent esophageal damage. Compared with higher powers, they require longer ablation durations to achieve a target lesion size index (LSI). Esophageal heating during ablation is the result of a time-dependent process of conductive heating produced by nearby radiofrequency delivery. This randomized study was conducted to compare risk of esophageal heating and acute procedure success of different LSI-guided ablation protocols combining higher or lower radiofrequency power and different target LSI values.

Methods:
Eighty consecutive patients were prospectively enrolled and randomized to one of 4 combinations of radiofrequency power and target LSI for ablation on the left atrium posterior wall (20 W/LSI 4, 20 W/LSI 5, 40 W/LSI 4, and 40 W/LSI 5). The primary end point of the study was the occurrence and number of esophageal temperature alerts per patient during ablation. Acute indicators of procedure success were considered as secondary end points. Long-term follow-up data were also collected for all patients.

Results:
Esophageal temperature alerts occurred in a similar proportion of patients in all groups. Significantly, shorter radiofrequency durations were required to achieve the target LSI in the 40 W groups. Less than 50% of the radiofrequency lesions reached the target LSI of 5 when using 20 W despite a longer radiofrequency duration. A lower rate of first-pass pulmonary vein isolation and a higher rate of acute pulmonary vein reconnection were recorded in the group 20 W/LSI 5. A lower atrial fibrillation recurrence rate was observed in the 40 W groups compared with the 20 W groups at 29 months follow-up.

Conclusions:
When guided by LSI, posterior wall ablation with 40 W is associated with a similar rate of esophageal temperature alerts and a lower atrial fibrillation recurrence rate at follow-up if compared with 20 W. These data will provide a basis to plan future randomized trials.

Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02619396.
Prognostic Impact of Residual Anatomic Disease Burden After Functionally Complete Revascularization
Authors: Lee Joo Myung , Hwang Doyeon , Choi Ki Hong , Lee Hyun-Jong , Song Young Bin , Cho Yun-Kyeong , Nam Chang-Wook , Hahn Joo-Yong , Shin Eun-Seok , Doh Joon-Hyung , Hoshino Masahiro , Hamaya Rikuta , Kanaji Yoshihisa , Murai Tadashi , Zhang Jun-Jie , Ye Fei , Li Xiaobo , Ge Zhen , Chen Shao-Liang , Kakuta Tsunekazu , Koo Bon-Kwon 
Published: September 2020

Background:
Prognostic impact of residual anatomic disease burden after functionally complete percutaneous coronary intervention (PCI), defined by post-PCI fractional flow reserve (FFR) >0.80 would be a clinically relevant question. The current study evaluated clinical outcomes at 2 years according to residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score (RSS) in patients who underwent functionally complete revascularization.

Methods:
A total of 1910 patients (2095 revascularized vessels) with post-PCI FFR >0.80 were selected from the International Post-PCI FFR Registry. RSS was defined as the SYNTAX score recalculated after PCI, SYNTAX revascularization index was calculated as 100×(1−RSS/pre-PCI SYNTAX score), and post-PCI FFR was measured after completion of PCI. The primary outcome was target vessel failure (TVF; a composite of cardiac death, target vessel–related myocardial infarction, and clinically driven target vessel revascularization) at 2 years, and risk of TVF was compared according to tertile classification of RSS (0, 1–5, and >5) and post-PCI FFR (≥0.94, 0.87–0.93, and ≤0.86).

Results:

After PCI, SYNTAX score was changed from 10.0 (Q1–Q3, 7.0–16.0) to 0.0 (Q1–Q3, 0.0–5.0) and FFR changed from 0.70±0.12 to 0.90±0.05. TVF at 2 years occurred in 4.9%, and patients with TVF showed higher pre-PCI SYNTAX score and lower post-PCI FFR than those without. However, there were no significant differences in SYNTAX revascularization index and RSS. The risk of TVF was not different according to tertile of RSS (log-rank
P
=0.851). Conversely, risk of TVF was different according to tertile of post-PCI FFR (log-rank
P
=0.009). Multivariable model showed the risk of TVF was significantly associated with post-PCI FFR (hazard ratio, 1.091 [95% CI, 1.032–1.153];
P
=0.002) but not with RSS (hazard ratio, 0.969 [95% CI, 0.898–1.045];
P
=0.417).

Conclusions:
Among patients who underwent functionally complete revascularization, residual anatomic disease burden assessed by RSS was not related with occurrence of TVF at 2 years. These results support the importance of functionally complete revascularization rather than angiographic complete revascularization.

Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT04012281.
Biometric and Psychometric Remote Monitoring and Cardiovascular Risk Biomarkers in Ischemic Heart Disease
Authors: Shufelt Chrisandra L. , Kim Andy , Joung Sandy , Barsky Lili , Arnold Corey , Cheng Susan , Dhawan Shivani , Fuller Garth , Speier William , Lopez Mayra , Mastali Mitra , Mouapi Kelly , van den Broek Irene , Wei Janet , Spiegel Brennan , Van Eyk Jennifer E. , Bairey-Merz C. Noel 
Published: September 2020

Background
Patients with stable ischemic heart disease represent a heterogeneous population at variable risk for major adverse cardiac events (MACE). Because MACE typically occurs outside the hospital, we studied whether biometric and psychometric remote patient monitoring are associated with MACE risk biomarkers.

Methods and Results

In 198 patients with stable ischemic heart disease (mean age 65±11 years, 60% women), we evaluated baseline measures, including biometric (FitBit 2) and psychometric (acquired via smartphone‐administered patient‐reported outcomes) remote monitoring, in the PRE‐MACE (Prediction, Risk, and Evaluation of Major Adverse Cardiac Events) study. In multivariable adjusted regression analyses, we examined the association of these measures with biomarkers of MACE risk, including NT‐proBNP (N‐terminal pro‐b‐type natriuretic peptide), u‐hs‐cTnI (ultra‐high sensitivity cardiac‐specific troponin I), and hs‐CRP (high‐sensitivity C‐reactive) protein. Both biometric and psychometric measures were associated with NT‐proBNP. Specifically, step count, heart rate, physical activity, global health score, and physical function score were all inversely related, whereas physical limitation score was directly related (
P
≤0.05 for all). However, only biometric measures (step count and heart rate) were associated with u‐hs‐cTnI (inversely related,
P
<0.05), while only the psychometric measures of physical limitation were associated with hs‐CRP (directly related,
P
≤0.05).

Conclusions
In stable ischemic heart disease patients, remotely monitored measures were associated with MACE risk biomarkers. Both biometric and psychometric measures were related to NT‐proBNP. In contrast, biometric measures were uniquely related to u‐hs‐cTnI, while psychometric indices were uniquely related to hs‐CRP. Further investigation could assess the predictive value of these metrics for MACE in ischemic heart disease.