bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of advance care planning in a resident run clinic in an underserved community.
Authors: Alexander Swetha Ann , Mathew Thomas Vinay , Wu David , Kulkarni Radhika , Rabitaille William 
Published: June 2021

e24067 Background: Advance Care Planning (ACP) ensures that patients receive care that is in line with their values and preferences. ACP is best done in the outpatient setting. Despite recognizing the importance of ACP, the rates of ACP completion continue to be low. We conducted a retrospective study to determine the rates of ACP in a resident run primary care clinic in Hartford, Connecticut, which serves the underserved community. We looked at patient characteristics to find correlation with ACP completion. We also aimed to determine the reasons which could decrease the completion of ACP. Methods: This was a retrospective chart review. Patients who met any of the inclusion criteria [i) Age>65 ii) End stage renal disease on dialysis iii) Metastatic/Recurrent cancer iv) End stage heart failure v) COPD Gold stage D] and were seen in the primary care clinic from September 1, 2019 to December 31, 2019 were selected. Their charts were reviewed to see if ACP was documented during primary care visits over the past two years. The demographics of the patients were noted. Subsequently, a survey was distributed to residents to determine the possible causes of low rates of ACP discussion. Results: The characteristics of the 373 patients included in the study are shown in Table 1. Only 14 (3.8%) of the 373 had documentation of ACP during their primary care visits. The characteristics of the 14 patients in whom ACP was done are as follows: Sex- Female 9/14 (64%); Ethnicity- Hispanic 10/14 (71%), African American 4/14 (29%); Religious Affiliation- Christian 13/14 (93%), None 1/14 (7%); Married/Partner 2/14 (14%). Patient demographics including sex (p 0.6), religious beliefs (p 0.8), and marital status (p 0.6) did not show any correlation with the likelihood of ACP completion. Of the 31 residents who answered the survey, the most commonly listed barriers to ACP completion were the following: lack of time to conduct these discussions (94%), forgetting to conduct ACP discussions (48%), and lack of training (19%). All the residents believed that ACP discussion was beneficial to patients and medical providers. Conclusions: The rates of ACP planning in our clinic are much lower than the national average. African American and Hispanics, who make up the majority of our clinic population, traditionally have had low rates of ACP completion. This is an important issue that needs to be addressed. Advance care planning training should be also be strengthened during residency. [Table: see text]
Overall survival (OS) and prognostic factors (PF) of patients (pts) with metastatic solid tumors admitted in intensive care unit (ICU).
Authors: Hautecloque-Raysz Segolene , Albert Thananayagam Marie , Martignene Niels , Le Deley Marie-Cecile , Penel Nicolas , Carnot Aurelien 
Published: June 2021

e24074 Background: Admission of cancer pts in ICU is a medical and ethical challenge, since there is no reliable prognostic tool for guiding decision making. Therefore, recent progress in cancer management improved the OS of advanced cancer pts, rendering this issue more and more frequent. Methods: We have retrospectively analyzed the medical charts of 129 consecutive pts treated in our institution and admitted in ICU from 01/2014 and 04/2019. We identified PF using Cox Models. We analyzed PF for OS or for ability to restart systemic treatment. Results: At the time of ICU admission, the mean age was 58.9 (range, 25-81). The were 51% of men. PS were 0-1 in 61% and 2-3 in 39%. The most prevalent cancers were lung (20%), sarcoma (17%), breast (16%) and gynecological cancers (11%). The number of metastatic sites was 1 (17%), 2 (39%), 3 (26%) and more (19%). The malignancy was stable in 69% and progressive in 31%. Pts currently received systemic treatment in 78%, were free of treatment in 5% and were not yet treated in 16%. Cancer itself (53%), toxicity of treatment (43%) and underlying comorbidities (37%) contributed to ICU admission. The number of organ failures was 0 in 12%, 1 in 40%, 2 in 26% and 3 or more in 22%. The 4 most symptoms were dyspnea (34%), severe infection (25%), cardiac event (23%) and bleeding (10%). Pt management required vasoamines administration (38%), ventilation (31%) and dialysis (4%). The median duration of stay in ICU was 4 days (range, 0-71). 21 (16%) pts died in ICU and 16 (12%) just after ICU discharge. 83 pts returned to home (64%). Systemic treatment was done in 61% of pts who left hospitalization alive after ICU. 1-month, 6-month and 12-month OS were 67, 36 and 21%, respectively. Multivariate analysis identified the following PF for OS: PS = 0 (HR = 0.57 [0.38-0.79]; p = .007), admission related to underlying comorbidity (HR = 0.63 [0.41-0.98], p = .0001) or admission related to treatment toxicity (HR = 0.31 [0.17-0.56] p = .0001). Multivariate identified 1 PF for ability to restart systemic treatment: one or less organ failure (HR = 0.34 [0.14-0.83], p = 0.02). Conclusions: In ICU, OS of adult pts with solid tumors looks like the non-cancer population. ¼ of admitted pts died in ICU or just after. Key PF were PS and cause of critical state. When ICU admission is related to cancer itself, the prognosis was poor.
A cross-sectional study on effectiveness of antiemetic regimens for chemotherapy-induced nausea and vomiting: A single-center retrospect study of 1,000 patients.
Authors: Cong Luo , Shang Mingge , Chen Lei , Qi Xu , Jingjing Li , Wei Qing , Ying Jieer 
Published: June 2021

e24100 Background: Chemotherapy-induced nausea and vomiting (CINV) is a common symptom in patients who undergoing chemotherapy, it is very important to control CINV to maintain dose intensity and patients' quality of life. To analyse the current situation of CINV for the tumor patients who undergoing chemotherapy, we used a cross-sectional survey to assess CINV status in those patients, and whether the drugs used by doctors in each department met the guidelines, and compared the efficacy of different antiemetic regimens on acute and delayed CINV overall post-chemotherapy periods. Methods: 1,000 patients were randomly selected from 5,468 patients with chemotherapy discharged from different departments of Zhejiang cancer hospital in China between April 1 and April 30, 2019, and there were 87 responses totally. Medical records were collected on patient’s department (internal medicine, surgery, radiotherapy, interventional), chemotherapy regimens, anti-vomiting program, etc. Patients' feedbacks were recorded by CTCAE4.03 standard using MASCC antiemetic tool (Mat). Participants reported the frequency, severity, and impact on daily life of CINV from the day of chemotherapy administration up to 5 days thereafter and nausea and vomiting, as well as pharmacologic and chemotherapy used. Results: A total of 66 antineoplastic drugs were investigated, of which 52 were given intravenously and 14 orally.There were 9, 7, 50 drugs with high, moderate and low emetic risk respectively.The most prescribed prophylactic regimens for the management of CINV were aprepitant, 5-HT3R, H1-RA and dexamethasone and metoclopramide. The overall incidence of CINV were 44.34%, 24.57% and 39.66% patients reported nausea or vomiting in the acute and delayed phases. 19.89% patients had both acute and delayed CINV. The consistency rate of antiemetic with guideline was 63.19% in internal medicine department, 61.41% in surgery department and 52.91% in radiotherapy department, which showed a significant gap between the actual use of drugs and the recommended guidelines(P = 0.001). In 875 patients, 518 patients received guideline recommended antiemetic regimen, the CINV rates of complete response (CR), defined as no vomiting with no rescue medication, were 61.58%. While the CR rates in other 357 patients were 47.06%(P < 0.001). Nausea was more frequent across the overall observation period (43.77% VS 18.86%). However, vomiting was more sever and had a greater impact on life than nausea. Conclusions: Overall, adherence to the guideline recommendations in different departments were poor with varying degrees. Future studies should set hard outcomes, such as the absence of any symptoms, as a primary end point. The standardized management of CINV in patients need to be further strengthened and doctors need to use drugs more regularly to reduce the occurrence of CINV in patients.
A phase II study to evaluate the safety and efficacy of OQL011 on VEGFR inhibitor-associated hand-foot-skin reaction in cancer patients.
Authors: Lacouture Mario E. , Anadkat Milan J. , Marathe Omkar Subhash , Vogelzang Nicholas J. , Lam Elaine Tat , Kaffenberger Benjamin , Choi Jennifer N. , Webb Mark L. , Tyler Robert Claude , Ju Juegang , Tang Hong , Luo Jie , Patel Anisha 
Published: June 2021

TPS12132 Background: Hand-Foot Skin Reaction (HFSR) is frequently associated with the use of multi-targeted tyrosine kinase inhibitors of the vascular endothelial growth factor receptor (VEGFRi) such as cabozantinib, regorafenib, sunitinib, and lenvatinib. HFSR affects the skin on the palms and soles and is manifested as edema, erythema, hyperkeratosis, and bullae, leading to a decrease in quality of life and interruptions in dosing. The incidence of HFSR differs among VEGFRi, ranging from 5-60% (all grades) and 1-18% (grade 3). To date, there is no FDA approved treatment for HFSR, and marginal benefit has been shown with topical urea or steroids. Although not fully elucidated, the pathogenesis of HFSR has been associated with impaired vascular repair mechanisms, caused by inhibition of VEGF signaling pathways. We hypothesize that topical stimulation of VEGFR through OQL011 will decrease the severity of HFSR symptoms via local upregulation of the VEGF/VEGFR related signaling pathways. Methods: NCT04088318 is a phase 2, double-blind, randomized controlled trial to evaluate the safety and efficacy of OQL011 compared to vehicle control in the treatment of moderate to severe HFSR in patients on VEGFRi therapy. Eligible patients will have ≥ grade 2 palmar plantar erythrodysesthesia (PPE). The study is expected to enroll 112 patients in two parts. In the first part, 42 patients will apply 0.2% OQL011 topical ointment or vehicle control (2:1 randomization) TID for six weeks. In Part 2, 70 subjects will be randomized into two additional dose levels or vehicle control in a 2:2:1 ratio. The two dose levels selected will be based on the efficacy and safety results of Part 1. The primary efficacy endpoint is improvement of NCI CTCAE v5.0 PPE to grade ≤1 by week 3. Photographs of the affected areas will be taken at Day 0, 7, 14, 21 and 42 timepoints. Superiority test will be performed to compare treatment groups, and the exposure-response relationship will be explored. In addition, an investigator global assessment (IGA) for HFSR will be used in this trial to specifically assess skin recovery and is proposed to be a new evaluation tool. The validity of IGA criteria will be evaluated by assessing the inter-rater and intra-rater reliability. The correlation between IGA, NCI CTCAE v5.0 for PPE, and patient reported outcomes including Visual Analog Scale of Pain, Hand-foot Quality of Life questionnaire will also be evaluated. This study began enrolling patients in December 2019 and is ongoing. Clinical trial information: NCT04088318.
Randomized double-blind, placebo-controlled study of topical diclofenac in prevention of hand-foot syndrome in patients receiving capecitabine.
Authors: Batra Atul , Santosh Akhil P. , Pramanik Raja , Gogia Ajay , Pandey R. M. , kumar akash , Sharma Atul 
Published: June 2021

TPS12135 Background: The pathophysiology of capecitabine induced hand-foot syndrome (HFS) includes activation of cyclooxygenase (COX)-2, leading to an upregulation of the inflammatory cascade. Prophylaxis with oral celecoxib was previously reported to be associated with a significantly lower frequency of HFS (grade 1 [29.0% vs. 72.0%, p < 0.001] and grade 2 [11.8% vs. 30.0%, p=0.024]) (1). The findings were confirmed in a phase III trial (2). However, the associated systemic adverse events limit routine prophylactic use. Till date, no clinical trials have assessed the role of topical non-steroidal anti-inflammatory drugs (NSAIDs) in preventing HFS. Methods: In this investigator-initiated randomised phase III double-blind, placebo controlled, parallel group trial, a total of 264 patients with any stage breast or gastrointestinal cancer planned to receive capecitabine as a single agent or in combination with other chemotherapy will be randomised (1:1) to 1% topical diclofenac or placebo (base for 1% topical diclofenac) arm at a single tertiary care cancer centre in India. Randomization will be done by stratified (male vs female, and capecitabine mono therapy vs combination) permuted block method using a computer generated random sequence and allocation concealment will be done by using sealed opaque envelopes. In both the arms, patients will be asked to apply 1 fingertip unit (FTU) of topical medication on both surfaces of bilateral hands twice daily for a total duration of 12 weeks or till development of grade 2 or higher HFS, whichever is earlier. The primary objective is to compare the effect of topical diclofenac with placebo in preventing clinically significant HFS (incidence of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 2 or higher HFS). The secondary objectives include comparison of topical diclofenac with placebo on (i) incidence of NCI CTCv5.0 all grade HFS, (ii) time to develop grade ≥2 HFS from start of capecitabine, (iii) patient-reported outcomes using HFS-14 questionnaire (iv) adherence with topical application using self-reported adherence diary, (v) capecitabine dose reductions, delays and cessation due to HFS and (vi) safety profile (NCICTCv5.0). The tertiary correlative endpoint is to correlate the occurrence and severity of HFS with serum COX-2 levels and polymorphism of dihydropyrimidine dehydrogenase (DPPD) enzyme. The trial is registered at the Clinical Trial Registry of India (CTRI/2021/01/030592). Till date, we have enrolled 12/264 patients. (1) Zhang RX et al. J Cancer Res Clin Oncol. 2011;137(6):953-957. (2) Zhang RX et al. Annals of oncology. 2012;23(5):1348-1353. Clinical trial information: CTRI/2021/01/030592.
A phase I study of AK119, an anti-CD73 monoclonal antibody, in combination with AK104, an anti-PD-1/CTLA-4 bispecific antibody, in patients with advanced or metastatic solid tumors.
Authors: Markman Ben , Hsieh Amy Hsin-Chieh , Coward Jermaine , Carlino Matteo S. , Frentzas Sophia , Jin Xiaoping , Li Baiyong , Wang Zhongmin Maxwell , Kwek Kon Yew , Xia Yu 
Published: June 2021

TPS2675 Background: AK119 is a humanized IgG1 monoclonal antibody (mAb) that selectively binds to and inhibits the ectonucleotidase activity of CD73, a cell surface enzyme that converts adenosine monophosphate (AMP) into adenosine. Adenosine has been shown to facilitate tumor-mediated evasion. CD73 inhibition may therefore reduce adenosine accumulation and promote anti-tumor immunity. AK104 is a recombinant humanized IgG1 bispecific antibody that simultaneously binds to programmed cell death protein 1 (PD-1) and cytotoxic T- lymphocyte-associated antigen protein 4 (CTLA-4). Preliminary data from phase I and II studies suggest that AK104 has encouraging anti-tumor activity in selected tumor types and an improved safety profile compared to the co-administration of anti-PD-1 plus anti-CTLA-4 mAbs. Preclinical studies show that CD73 inhibition synergistically increases the anti-tumor activity of PD-1 and CTLA-4 immune checkpoint inhibitors (ICIs). Published early clinical data suggests that anti-CD73 therapy in combination with ICIs produces improved clinical outcomes. Thus, AK119 plus AK104 is postulated to have synergistically enhanced anti-tumor activity compared to the administration of anti-CD73 monotherapy or ICIs alone. Methods: This is a phase 1a/1b, first-in-human, multicenter, open-label study in patients with advanced solid tumors that are refractory to standard therapies. The primary objective is to assess safety, tolerability and dose limiting toxicity; and to determine the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of AK119 in combination with AK104. Secondary objectives are to evaluate antitumor activity, PK and AK119 immunogenicity. The dose-escalation phase will evaluate 5 dose levels of AK119 (1mg/kg to 40 mg/kg Q2W IV) in combination with 6mg/kg AK104 Q2W IV using a 3+3+3 study design. Eligible pts will receive a single dose of AK119 on C0D1 of a 14-day “lead-in” period. Thereafter, from C1D1 pts will receive AK119 in combination with AK104 on a 28-day cycle, until unacceptable toxicity, confirmed progressive disease, subject withdrawal, or for a maximum of 24 months. The “lead-in” period is only applicable for dose-escalation cohorts. Any dose-escalation cohort not exceeding the MTD may be expanded to a maximum of 18 subjects with selected solid tumor types for further evaluation of safety, PK/ PD, immunogenicity, and preliminary anti-tumor activity. Cohort 1 is currently in progress with the first patient enrolled in January 2021. For the dose-expansion phase, cohorts of pts with advanced/metastatic pancreatic cancer or MSS/pMMR colorectal cancer will be enrolled. Cohorts of other tumor types may be added based on emerging pharmacodynamic and anti-tumor response data. Clinical trial information: NCT04572152.
A phase II open-label study of cpi-613 in combination with modified (m)FOLFIRINOX in patients with locally advanced pancreatic cancer.
Authors: Bajor David Lawrence , MOHAMED AMR , Selfridge J. Eva , Anderson Erin E. , Hardacre Jeffrey , Ammori John Brian , Lee Richard T. , Saltzman Joel N. , Winter Jordan Michael 
Published: June 2021

TPS4176 Background: For patients with locally advanced pancreatic cancer, neoadjuvant trials are the preferred strategy. The goals of neoadjuvant treatment are to diminish the size of the primary tumor to allow for safe surgical resection and to limit the chance of developing metastatic disease. mFOLFIRINOX is the gold-standard for treatment in the adjuvant setting and an acceptable regimen in the neoadjuvant setting with many ongoing neoadjuvant trials using it as a chemotherapeutic backbone. CPI-613 (devimistat) is a small-molecule inhibitor of pyruvate dehydrogenase and alpha-ketogluterate dehydrogenase that has been studied in combination with mFOLFIRINOX in a phase I trial of patients with metastatic pancreas cancer and shown to be safe at the proposed phase II dose. Methods: This is a single-center, single-arm phase II trial for patients with locally advanced pancreatic cancer; defined as either borderline resectable or unresectable according to NCCN guidelines and interpreted by the primary investigator. Patients with metastatic disease are excluded. Patients will receive treatment with CPI-613 and mFOLFIRINOX per the table below. The primary endpoint is overall survival. Secondary endpoints are progression free survival and resection rate. At the time of submission this study has completed initial accrual with 37 patients enrolled. Clinical trial information: NCT03699319. [Table: see text]
Single-shot ultrasound-modulated optical tomography with enhanced speckle contrast
Authors: Yuan Dean , Luo Jiawei , Wu Daixuan , Zhang Runsen , Lai Puxiang , Li Zhaohui , Shen Yuecheng 
Published: June 2021

Ultrasound-modulated optical tomography (UOT) images optical contrast deep inside biological tissue. Among existing approaches, camera-based parallel detection is beneficial in modulation depth but is limited to the relatively slow framerate of cameras. This condition prevents such a scheme from achieving maturity to image live animals with sub-millisecond speckle correlation time. In this work, we developed on-axis single-shot UOT by investigating the statistics of speckles, breaking the restriction imposed by the slow camera framerate. As a proof of concept, we experimentally imaged a one-dimensional absorptive object buried inside a moving scattering medium with speckle correlation time down to 0.48 ms. We envision that this single-shot UOT is promising to cope with live animals with fast speckle decorrelation.
Femtosecond multi-10-mJ pulses at 2 µm wavelength by compression in a hollow-core fiber
Authors: Nagy Tamas , von Grafenstein Lorenz , Ueberschaer Dennis , Griebner Uwe 
Published: June 2021

High-energy few-ps pulses from a Ho:YLF chirped pulse amplifier operating at a 1 kHz repetition rate are compressed in a two-stage arrangement to sub-90-fs duration. The energy of the compressed pulses is more than 20 mJ at an average power of 20 W. In the first stage, the duration of the 2.8 ps, 40 mJ pulses at 2.05 µm wavelength was reduced to 1.4 ps by using nonlinear propagation in air. Subsequently, the pulses were further compressed to 86 fs after spectral broadening in a 3-m-long Kr-filled stretched flexible hollow-core fiber. The high photon flux, peak power, and excellent beam quality and stability make this light source highly attractive for fs pulse generation in the extreme ultraviolet (XUV) to x-ray spectral range for time-resolved XUV spectroscopy or measurements of structural dynamics in solids.
Double-pass pre-chirp managed amplification with high gain and high average power
Authors: Zhang Yao , Wang Jingshang , Teng Hao , Fang Shaobo , Wang Junli , Chang Guoqing , Wei Zhiyi 
Published: June 2021

We demonstrate, to the best of our knowledge, the first double-pass pre-chirp managed fiber amplifier. The double-pass fiber amplifier exhibits high gain allowing us to amplify chirped picosecond pulses from 20 mW to 113 W in a rod-type Yb-fiber corresponding to 38 dB gain. We study the dependence of static mode degradation (SMD) on the nonlinear phase shift (NPS) accumulated by the amplified pulse. Our results indicate that a larger nonlinear phase shift results in stronger nonlinear polarization evolution of the fundamental mode and leads to a lower threshold for SMD. After optimization, our pre-chirp managed amplifier seeded by 80 mW pulses delivers 102 W amplified power from the main output. The amplified pulses are compressed to 37 (55) fs with 90 (100) W average power by a grating pair (chirped mirrors). The double-pass configuration significantly simplifies the implementation of pre-chirp managed fiber amplifiers leading to an extremely compact system.