bluuebunny/crossref_metadata_2025_split huggingface dataset:
The interplay between left ventricular diastolic and right ventricular dysfunction: challenges in the interpretation of critical care echocardiography studies
Authors: La Via Luigi , Merola Federica , Schembari Giovanni , Liotta Calogero , Sanfilippo Filippo 
Published: January 2023

Abstract
Background
Sepsis is a leading cause of death and it is characterized not only by profound vasoplegia but also by myocardial dysfunction. Critical care echocardiography is the preferred modality for the initial assessment of the cause of shock. Moreover, it can be extremely helpful in the identification of progressing myocardial dysfunction during the course of sepsis, also known as septic cardiomyopathy.

Main body
One of the issues in the identification of septic cardiomyopathy is that it can be manifest with different clinical phenotypes, from overt biventricular dysfunction to isolated left ventricular (LV) systolic and/or diastolic dysfunction, from right ventricular (RV) systolic dysfunction to RV failure and dilatation. However, the commonly used echocardiography parameters for the assessment of LV and/or RV function are not always entirely reliable. Indeed, these are influenced by variable preload and afterload conditions imposed by critical illness such as fluid shifts, sedation level and mechanical ventilation with positive pressure.

Conclusions
Strain echocardiography is a promising tool for the early identification of myocardial dysfunction in the context of sepsis. Studies reporting data on strain echocardiography should be particularly detailed in order to increase the reproducibility of results and to favor comparison with future studies.
Telehealth in long-term care facilities during the Covid-19 pandemic – Lessons learned from patients, physicians, nurses and healthcare workers
Authors: Dai Zhaoli 
Published: January 2023

Abstract
Background
Telehealth and telecare are particularly important and beneficial to long-term care facilities due to care demands, workforce, and the unique environment. Stemming from the recent findings on telehealth utilisation in residential aged-care facilities in Australia, this commentary seeks to identify lessons and perspectives learned during the Covid-19 pandemic from multiple users, including patients, physicians, nurses, and healthcare workers in long-term care (LTC) settings.

Main body
From patients’ perspectives, older adults residing in LTC settings often opt not to use virtual care, with the majority preferring in-person visits. This is despite residents expressing their willingness to use telehealth, and virtual care has advantages in LTC settings or in remote areas. Additionally, hearing, vision, or cognitive impairment can limit residents’ ability to use information technology to access care, so their preferences for phone or video consultations depend on the health conditions or care requirement. From physicians’ perspectives, most healthcare practitioners have a positive attitude toward using telehealth. However, telephone consultations tended to be the dominant mode during the early period of the Covid-19 pandemic. Physicians also raised several major concerns, including technical and equipment-related issues, expanded roles, or additional workloads of LTC staff that could negatively affect clinical decision-making and unequal access in rural, older, and cognitively impaired patients. Most nurses and healthcare workers perceived telehealth positively as a way to enhance patients’ care access. However, the majority had concerns about acquiring appropriate knowledge of using the technology for themselves and their patients. In remote areas, nurses expressed higher efficiency and higher care quality when utilising telehealth in caring for older patients than in the regular in-person care mode.

Conclusion
Since the beginning of the Covid-19 pandemic, telehealth has continued as an alternative platform in clinical services. However, as a healthcare platform that offers flexibilities of time, location, and improved efficiency, changing the traditional mindset is essential to shift the paradigm to use telehealth when appropriate. Importantly, telehealth needs substantial support in rural or remote long-term care facilities. Doing so will contribute to the reduction of healthcare inequity in long-term care facilities in remote settings and those with social disparities.
Bevacizumab in first-line therapy in lung metastases of colorectal cancer: An ARCAD pooled analysis.
Authors: Shmueli Einat S , Raeisi Morteza , Chibaudel Benoist , Hurwitz Herbert , Saltz Leonard B. , Kabbinavar Fairooz F. , Tebbutt Niall C. , Grothey Axel , Adams Richard , Zalcberg John Raymond , Yoshino Takayuki , Bachet Jean-Baptiste , Cohen Romain , Sharara Lama , Andre Thierry , Shi Qian , De Gramont Aimery 
Published: January 2023

118 Background: Anti-VEGF is widely used in the treatment (trt) of metastatic colorectal cancer (mCRC). Only studies with bevacizumab (BEV) have shown survival benefit (bnf) in first line trt. The magnitude of bnf might differ based on the metastatic (met) site and the chemotherapy regimen (CTR) with which BEV is partnered. ARCAD database contains individual patient data (IPD) of randomized trials that evaluated BEV+ CT. In this pooled analysis, we aimed to evaluate BEV bnf in mCRC with lung metastases (mets) either as single or multiple sites. Methods: IPD from four trials (AVF2107g, N016966, AVF2192g, AGITG) comparing CT +/- BEV were pooled. The primary endpoint, overall survival (OS), was estimated using Kaplan-Meier method and prognostic value of lung mets was evaluated by stratified Cox models according to number and type of met sites and CTRs, oxaliplatin or irinotecan (OX/IRI) based. The predictive bnf of BEV was evaluated by interaction test (int) between trt and lung mets status in subgroups and considered as significant (sig) with a P < 0.1. Results: 2728 patients (pts) with known met sites and survival data were pooled. 1020 pts had single met site, 133 had only lung mets. 1708 pts had multiple met sites, 1008 had lung mets. Pts characteristics were well balanced. Sig OS bnf of BEV was observed in the whole population. In pts subgroup according to the presence or absence of lung mets, sig bnf of BEV were observed with a non-sig int ( Pint=.590). Non-sig bnf of BEV was observed in pts with single site regardless of met site (lung or no lung) or CTR. Sig bnf of BEV was observed in pts with multiple sites without lung mets whatever the CTRs. While sig bnf of BEV was observed in pts with multiple sites with lung mets, we found a sig int between BEV and OX/IRI-based regimens ( Pint=.022). The bnf of BEV was observed with IRI-based regimen but not in OX-based regimen. The bnf of BEV appears greater in multiple sites without lung mets than with lung mets with a sig stratified log-rank test ( PLRT<.001). Conclusions: In pts with multiple sites mCRC, a statistically sig OS bnf of BEV added to CT was observed mainly among pts without lung mets. The overall effect of CT partner choice when combined with BEV can be different. In pts with single site, BEV did not seem to improve OS but the evaluation of efficacy of BEV in presence or absence lung mets was based on small number of pts and needs to be evaluated in trials with larger pts sample, especially trials including pts with single site lung mets. [Table: see text]
A double-blind, randomized, placebo-controlled, parallel study to investigate the auxiliary effects of fucoidan in patients with locally advanced rectal cancer who receive neoadjuvant concurrent chemoradiotherapy before surgery.
Authors: Wang Jaw-Yuan , Tsai Hsiang-Lin 
Published: January 2023

12 Background: Preoperative concurrent chemoradiotherapy (CCRT) is the standard treatment for patients with locally advanced rectal cancer (LARC). Low molecular weight fucoidan (LMF) is widely used as food supplements in cancer patients. This study is aimed to evaluate the efficacy of LMF as supplemental therapy to CCRT in LARC patients. Methods: We conducted a double-blind, prospective, randomized, placeo-controlled study to investigate the auxiliary effects of fucoidan in 107 patients with LARC who receive neoadjuvant CCRT before surgery. Finally, 87 patients were enrolled, of whom 44 were included in the study (fucodin) group and 43 in the control (placebo) group. The primary endpoint was the EORTC QLQ-C30 and FACT-C quality of life (QoL), and secondary endpoints included the overall response rate (ORR), disease control rate (DCR) and adverse events (AEs). Results: The physical well-being (PWB) was much improved after 2-month administration in the study (fucodin) group when compared with placebo group ( P= 0.007), whereas colorectal cancer subscale (CCS) was also better after 3-month administration when compared with placebo group ( P= 0.034). ORR and DCR were not significantly different between 2 groups (both P > 0.05). Moreover, skin rash ( P= 0.038) and fatigue ( P= 0.008) was less common in the fucodin group. Conclusions: This is the first clinical trial evaluating the efficacy of LMF as a supplemental therapy in the management of patients with LARC who undergoing CCRT. The results indicate that LMF would significantly improve QoL and decrease AEs of skin rash/fatigue; however, a long-term follow up is mandatory for the confirmation of oncological outcomes by LMF. Clinical trial information: NCT04342949 .
Predictive and prognostic features of metastatic colorectal cancer arising from the transverse colon: A pooled analysis of the CCTG/AGITG CO.17 and CO.20 randomized trials.
Authors: Solar Vasconcelos Joao Paulo , Chen Nan , Tu Dongsheng , Brule Stephanie Yasmin , Goodwin Rachel Anne , Jonker Derek J. , Price Timothy Jay , Zalcberg John Raymond , Moore Malcolm J. , Karapetis Christos Stelios , Siu Lillian L. , Shapiro Jeremy David , Simes John , O'Callaghan Christopher J. , Loree Jonathan M. 
Published: January 2023

124 Background: Primary tumour location is predictive of anti-EGFR benefit and prognostic in metastatic colorectal cancer (mCRC). Transverse colon cancers are often categorized as right sided, but the optimal cut point is unclear. Canadian Cancer Trials Group (CCTG)/Australasian Gastro-Intestinal Trials Group ( AGITG) CO.17 compared Cetuximab (Cet) vs. best supportive care (BSC) in mCRC. CCTG/AGITG CO.20 studied the addition of Brivanib Alaninate to Cet in pre-treated KRAS wildtype (WT) mCRC. We investigated the predictive and prognostic features of transverse colon primary location in a pooled cohort from these trials. Methods: Data from patients with RAS WT mCRC from CO.17 and KRAS WT mCRC from CO.20 randomized to cetux were analyzed for treatment outcomes according to location - right, transverse and left. The cecum to transverse colon was considered right sided, while the splenic flexure to rectum was considered left sided. Results: 553 patients were included, 201 (36.3%) from CO.17 and 352 (63.7%) from CO.20. Primary site distribution was: 32 (5.8%) transverse, 101 (18.3%) right and 420 (75.9%) left. On multivariate analysis from 457 (82.6%) patients treated with Cet, left side was associated with superior OS (HR, 0.40; 95% CI, 0.24-0.68, p=0.0006) and PFS (HR, 0.48; 95% CI,0.29-0.79, p=0.004) compared to transverse colon. No significant difference was noted in OS (HR, 0.74; 95% CI, 0.41-1.31, p=0.30) and PFS (HR, 0.79; 95% CI, 0.46-1.36, p=0.40) between right side versus transverse colon. Sidedness was not associated with prognostic difference in OS or PFS in the 96 (17.4%) patients receiving BSC alone. Outcomes according to primary site and treatment are shown. Conclusions: Transverse mCRC has comparable prognostic and predictive features to right sided mCRC. In keeping with previous studies, left side was predictive of greater Cet benefit and presented better overall prognosis when single agent Cet was used after 5-FU, oxaliplatin and irinotecan. [Table: see text]
Association of patient and disease characteristics with outcomes of regorafenib in patients with metastatic colorectal cancer.
Authors: Hsieh Ronan Wenhan , Lee Matthew , Johnson Devin , Zhang Chenxin , Moon Jee-Young , Hsu Dennis , Acuna-Villaorduna Ana , Kuang Chaoyuan 
Published: January 2023

135 Background: Regorafenib (rego) is a multikinase inhibitor approved for use in metastatic colorectal cancer (mCRC). No predictive biomarkers have been identified for rego. We conducted a real-world multi-institutional retrospective study to identify the patient and tumor characteristics associated with outcomes of rego in mCRC patients. Methods: Patients from University of Pittsburgh Medical Center and Montefiore Medical Center who received rego for mCRC were included. Patient characteristics, tumor pathology and molecular profiles, treatment history, and response to rego were collected. Primary and secondary outcomes were best objective response and progression free survival (PFS) on rego, respectively. Univariate and multivariate analyses were conducted using Fisher’s exact test, Mann-Whitney U test, Firth logistic regression and Cox proportional-hazards model. Results: 76 patients were included (median age 64, 42% females, 84% whites). Rego yielded a disease control rate of 32% (including 2 complete responses) and a median PFS of 3.6 months. Tumors with high microsatellite instability (MSI-H) had a significantly lower odds of progression of disease (POD) as best objective response (p = 0.01) and a significantly longer median PFS (p = 0.022) compared with tumors with microsatellite stability (MSS) in multivariable models (Table). 75% of MSI-H mCRC patients had not received immunotherapy (IO) prior to rego. Presence of peritoneal carcinomatosis and older age were associated with higher odds of POD (p = 0.093) and a significantly shorter PFS (p = 0.029), respectively. Compared to Whites, Black patients had a numerically higher odds of POD and shorter PFS. Sex, smoking, alcohol, sidedness of CRC, previous treatments, organs involved, and KRAS mutation were not associated with treatment response or PFS. Conclusions: Our study showed that MSI-H mCRC was associated with significantly better response to rego and PFS, even in the absence of prior IO. Other predicting factors for worse outcomes of rego included older age, and potentially peritoneal carcinomatosis and Black race. None of the mutations was found associated with treatment outcomes, with the limitation of lack of comprehensive molecular testing in many patients. Studies to further examine potential biomarkers such as MCL-1 and FBW7 mutations and correlation to clinical outcomes are ongoing. [Table: see text]
Outcomes of patients (pts) with metastatic colorectal cancer (mCRC) participating in phase I clinical trials: The Sarah Cannon Research Institute UK experience.
Authors: Ignatova Ekaterina , Fontana Elisa , Luo Siyun , Williams Anja , Arkenau Hendrik-Tobias 
Published: January 2023

142 Background: In the last decade immunotherapy, BRAF inhibitors (inh) and trifluridine-tipiracil became new standard of care (SoC) options for selected mCRC pts through the drug development pathway. In this study we aimed to evaluate clinical characteristics and outcomes of pts with mCRC participating in phase I trials. Methods: Electronic medical records from 10/2011 to 07/2022 were reviewed; pts who received at least one dose of trial drug were included. Data were analysed with descriptive statistic. Results: 81 (100%) pts were identified; 38 (47%) female; median age: 59 (range 31-80); 31 pts (38%) - right sided; 35 (44%) - RASmut, 29 (36%) - BRAFmut, 16 (20%) - RAS/BRAFw; MSI-H status was detected in 11 pts. Eleven pts participated in >1 trial, for a total of 96 cases. Median follow-up was 7 months (m); overall response rate was 6.8%, mPFS: 2.9 m, mOS 18.8 m. Age<50 (P=0,02), low lymphocyte/monocyte ratio (LMR ≤2.8) (P=0.02), in-situ primary tumour (P<0.001), no adjuvant therapy (P=0,001), right sided tumour (P=0,02) were independently associated with shorter OS (univariate analysis); the last three variables remained significant in multivariate analysis. Outcomes according to 4 drug classes and others (chemotherapy-based +/- targeted agents) are shown. Conclusions: Phase 1 trials offer a reasonable therapeutic approach for pts with mCRC and early access to drugs with potential to become SoC in future. [Table: see text]
Neoadjuvant chemoradiation does not improve outcomes for patients undergoing resection for upper rectal cancer: A US Rectal Cancer Consortium analysis.
Authors: Medin Caroline , Gamboa Adriana C. , Warren Emilie , Regenbogen Scott E. , Hendren Samantha , Holder-Murray Jennifer , Kalady Matthew , Ejaz Aslam , Hawkins Alexander , Silviera Matthew , Maithel Shishir K. , Balch Glen C. 
Published: January 2023

143 Background: The use of neoadjuvant chemoradiation (NCRT) for upper rectal cancer remains controversial. Our aim was to determine whether NCRT was associated with improved outcomes. Methods: The US Rectal Cancer Consortium was queried for patients who underwent resection of non-metastatic upper rectal cancer (≥12cm from anal verge) from 2007-2017. Primary outcomes were recurrence-free (RFS) and overall survival (OS). Secondary outcomes were postoperative complications. Results: 193 pts met inclusion criteria; 100 (52%) did not receive NCRT and 93 (48%) did. Median age was similar between groups (non-NCRT: 62 yrs; NCRT: 57 yrs; p=0.71). Patients in each group had similar gender and pathological stage (non-NCRT: 22% stage I, 32% stage II, 36% stage III; NCRT: 21% stage I, 23% stage II, 33% stage III; p=0.143). Median follow-up was 31 months (non-NCRT) and 34 months (NCRT). On Kaplan-Meier analysis, NCRT was not associated with improved RFS compared to non-NCRT (3-year RFS 85% vs. 80%; p=0.34) or OS (3-year OS 88% vs. 90%; p=0.49). This finding persisted on multivariable cox regression. R0 resection rate was similar between groups at 99% (non-NCRT) and 97% (NCRT; p=0.27). Anastomotic leak occurred in 11% of both cohorts. Creation of a diverting loop ileostomy (DLI) was nearly 3 times higher in NCRT (82%) versus non-NCRT patients (29%; p<0.001). Conclusions: Among patients with non-metastatic upper rectal cancer, NCRT did not improve survival or recurrence rates, but was associated with a nearly threefold higher DLI rate. Although NCRT is a mainstay of treatment for lower rectal cancer, our results do not support its use in upper rectal cancer. [Table: see text]
Phase II study of TAS-OX (TAS-102 and oxaliplatin) plus bevacizumab for late-line colorectal cancer.
Authors: Hochster Howard S. , Liu Hao , Berim Lyudmyla Derby , Spencer Kristen Renee , Gulhati Pat , DiRubbo Manda , Cohen Seth D. , Lee Patrick , Leitner Stuart P. , Radovich Delia , Misdary Christian , Perez Christian , Datta Sutirtha , Gonzalez Andrea , Saunders Tracie , Boland Patrick M 
Published: January 2023

144 Background: TAS-102 (trifluridine/tipiracil) is a novel oral antimetabolite for late line metastatic colorectal cancer (CRC) approved in 2018. Many patients are treated early in their course with oxaliplatin (OX), particularly adjuvant, and may benefit from re-treatment. In this trial we combine the typical late line use of TAS with OX (BEV [bevacizumab] added at investigator discretion) with goal of improved response. Methods: Eligibility included measurable CRC previously treated with all approved drugs per TAS package insert (irinotecan, oxaliplatin, 5FU, anti-VEGF, anti-EGF) as appropriate, PS = 0-1, labs within usual range, neuropathy < grade 2, ability to take oral meds, appropriate contraception. If no contraindication to BEV, this could be added at patient. TAS was dosed at 35 mg/m2 days 1-5 with OX 85/m2 d1 every 14 days (and BEV 5 mg/kg, if given). All supportive care was allowed including growth factors. Results: 47 patients (pts, median age 55) were enrolled in a Simon mini-max design, including 45% female, 21% black, 11% Asian, 11% Hispanic and 5% mixed. 26 pts received BEV. For the first 40 pts, 385 cycles were given (mean = 7 cycles, median 8) with 18 pts (45%) requiring dose reductions (1 dose reduction = 9 pts, 2 = 6, 3 = 3), and 9 receiving (peg)/filgrastim. Toxicities leading to SAEs included gr 3 heme (2), heart failure, abd pain/n/v (6), sepsis (2), urinary (4); and related gr 3 included one gr 3 vomiting and one gr 3 neutropenia. Independently reviewed RECIST Response (N = 32) included PR 2(6%), SD 23 (72%), PD 7 (22%). Mean TTP was 4.5 m (median 4, range 1 – 18) with 9 (28%) pts more than 6 months. Conclusions: In patients with late-line CRC and candidates for TAS (trifluridine/tipiracil), treatment with TAS plus OX is both well tolerated and active. RR is higher than single agent and 78% (95% CI, 60-91%) of patients had stable disease or response, with 60% receiving 8 or more cycles. Randomized trials comparing to single agent TAS are warranted in this setting. Clinical trial information: NCT04294264 .
Prospective evaluation of dose-escalated preoperative concurrent chemo-radiation with image-guided intensity modulated radiation therapy in locally advanced rectal cancers.
Authors: Puri Raunaq , Rastogi Madhup , Gandhi Ajeet Kumar , Khurana Rohini , Hadi Rahat , Sapru Shanyanu , Srivastava Anoop , Bharati Avinav , Mishra Surendra Prasad 
Published: January 2023

155 Background: The paradigm of locally advanced (T3/4; T1-4N1-2) rectal cancers (LARC) requires an intensified treatment for better pathological outcomes. Treatment intensification may be done by radiation dose escalation of long course neoadjuvant chemoradiation therapy (NACRT) by image guided Intensity Modulated Radiation Therapy (IG-IMRT) to increase downstaging with potentially higher local control rates. We aimed to analyze the efficacy and safety of NACRT with dose escalated IG-IMRT in LARC. Methods: 20 patients of LARC were recruited in this prospective interventional phase-II study treated by IG-IMRT with 45 Gray/25 fractions to elective nodal volumes and concomitant boost of 55 Gray/25 fractions to gross primary and nodal disease with concurrent capecitabine (825 mg/m2 twice a day on radiation days). All were planned to undergo definitive surgery 6-8 weeks post completion of NACRT with Total mesorectal excision by Low anterior resection (LAR) or Abdominoperineal resection (APR) followed by 6-8 cycles of adjuvant chemotherapy. Post operative response assessment was assessed by Modified Ryan’s scheme for regression and by tumor downstaging. Primary end point was acute toxicity assessment and secondary end points were pathological complete response (pCR) and loco-regional control (LRC). Results: Of 20 patients, 18 underwent definitive surgery and received full course adjuvant chemotherapy (90%). Median follow up was 15.1 months. 2 patients refused surgery, had complete clinical response (cCR) on assessment and were on follow up. Tumor downstaging was achieved in 14 (77.7%) patients and nodal downstaging was achieved in 15/18 (83.3%) patients. In 4 patients (22.2%) pCR was achieved and overall complete response (OCR defined as pCR and nearCR, including 2 patients with cCR) in 10 patients (50%). 4 patients planned for APR underwent LAR achieving a sphincter preservation rate of 22%. Grade 3 toxicities were observed in 2 patients which resolved on first follow up. No Grade 4 acute toxicities were reported. No loco-regional relapses were found and all patients are disease free at the time of last follow up. Conclusions: Dose escalation with IG-IMRT offers higher rates of pCR and OCR with acceptable toxicity profile and excellent short term locoregional control. [Table: see text]