bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative hemoglobin and perioperative blood transfusion in major head and neck surgery: A systematic review and meta-analysis
Authors: Ali Munib , Dort Joseph C. , Sauro Khara M. 
Published: January 2023

Background There is a growing concern with inappropriate, excessive perioperative blood transfusions. Understanding the influence of low preoperative hemoglobin (Hgb) on perioperative blood transfusion (PBT) in head and neck cancer (HNC) surgery with free flap reconstruction may help guide clinical practice to reduce inappropriate treatment among these patients. The objective is to synthesize evidence regarding the association between preoperative Hgb and PBT among major HNC free flap surgeries. Methods Terms and synonyms for HNC surgical procedures, Hgb and PBT were used to search MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials and Cochrane Database of Reviews from inception to February 2020. Reference lists of included full texts and studies reporting the preoperative Hgb, anemia or hematocrit (exposure) and the PBT (outcome) in major HNC surgery with free flap reconstruction were eligible. Studies examining esophageal, thyroid and parathyroid neoplasms were excluded; as were case reports, case series (n < 20), editorials, reviews, perspectives, viewpoints and responses. Two independent, blinded reviewers screened titles, abstracts and full texts in duplicate. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was followed. A random-effects model was used to pool reported data. The primary outcome was the proportion of patients who had a PBT. Subgroup analysis examined sources of heterogeneity for perioperative predictors of PBT (age, sex, flap type, flap site and preoperative Hgb). We also examined mean preoperative Hgb in the PBT and no PBT groups. Results Patients with low preoperative Hgb were transfused more than those with normal Hgb (47.62%, 95% CI = 41.19–54.06, I2 = 0.00% and 13.92%, 95% CI = 10.19–17.65, I2 = 20.69%, respectively). None of the predictor variables explained PBT. The overall pooled mean preoperative Hgb was 12.96 g/dL (95% CI = 11.33–14.59, I2 = 0.00%) and was 13.58 g/dL (95% CI = 11.95–15.21, I2 = 0.00%) in the no PBT group and 12.05 g/dL (95% CI = 10.01 to 14.09, I2 = 0.00%) in the PBT group. Conclusions The heterogeneity between studies, especially around the trigger for PBT, highlights the need for additional research to guide clinical practice of preoperative Hgb related to PBT to enhance patient outcomes and improve healthcare stewardship. Graphical Abstract
Prevalence of Internet gaming disorder and its association with psychiatric comorbidities among a sample of adults in three Arab countries
Authors: Almutairi Tourki Abdulmhsen , Almutairi Khaled Sultan , Ragab Khaled Mohamed , Nourelden Anas Zakarya , Assar Ahmed , Matar Sajeda , Rashid Hivan Haji , Elsayed Mohamed , Fathallah Ahmed Hashem , Spitzer Manfred , Schönfeldt-Lecuona Carlos ,   Collaboration Team, Albazee Ebraheem , Klib Mohamad , Hassan Zeina Mohammed 
Published: January 2023

Abstract

Background
As Internet gaming became publicly available over the past 25 years, Internet gaming disorder emerged as a new diagnostic entity and became established in psychiatric diagnostic systems as a form of addiction. Given the recency of its advent, reliable data on the epidemiology and psychiatric comorbidity of this disorder in specific geographic regions are scarce and dearly needed for appropriate treatment.

Results
A total sample of number = 1332 participants completed the questionnaire. Four-hundred twenty-three of them were gamers; in this cohort, the prevalence of Internet gaming disorder was 6.1%. A strong association between Internet gaming and several psychiatric disorders (attention deficit, hyperactivity, depression, and anxiety) was found.

Conclusions
Internet gaming disorder is frequent in adults from Arab countries. It is associated with psychiatric comorbidities in this current sample; the nature of this association needs to be properly investigated.
In vivo serotonin 1A receptor hippocampal binding potential in depression and reported childhood adversity
Authors: Bartlett Elizabeth A. , Yttredahl Ashley A. , Boldrini Maura , Tyrer Andrea E. , Hill Kathryn R. , Ananth Mala R. , Milak Matthew S. , Oquendo Maria A. , Mann J. John , DeLorenzo Christine , Parsey Ramin V. 
Published: January 2023

Abstract

Background
Reported childhood adversity (CA) is associated with development of depression in adulthood and predicts a more severe course of illness. Although elevated serotonin 1A receptor (5-HT1AR) binding potential, especially in the raphe nuclei, has been shown to be a trait associated with major depression, we did not replicate this finding in an independent sample using the partial agonist positron emission tomography tracer [11C]CUMI-101. Evidence suggests that CA can induce long-lasting changes in expression of 5-HT1AR, and thus, a history of CA may explain the disparate findings.

Methods
Following up on our initial report, 28 unmedicated participants in a current depressive episode (bipolar n = 16, unipolar n = 12) and 19 non-depressed healthy volunteers (HVs) underwent [11C]CUMI-101 imaging to quantify 5-HT1AR binding potential. Participants in a depressive episode were stratified into mild/moderate and severe CA groups via the Childhood Trauma Questionnaire. We hypothesized higher hippocampal and raphe nuclei 5-HT1AR with severe CA compared with mild/moderate CA and HVs.

Results
There was a group-by-region effect (p = 0.011) when considering HV, depressive episode mild/moderate CA, and depressive episode severe CA groups, driven by significantly higher hippocampal 5-HT1AR binding potential in participants in a depressive episode with severe CA relative to HVs (p = 0.019). Contrary to our hypothesis, no significant binding potential differences were detected in the raphe nuclei (p-values > 0.05).

Conclusions
With replication in larger samples, elevated hippocampal 5-HT1AR binding potential may serve as a promising biomarker through which to investigate the neurobiological link between CA and depression.
Cesarean section and parenting stress: Results from the Japan Environment and Children’s Study
Authors: Matsumura Kenta , Hatakeyama Takehiro , Yoshida Taketoshi , Tsuchida Akiko , Inadera Hidekuni ,   The Japan Environment and Children’s Study (JECS) Group
Published: January 2023

Abstract

Background
Accumulating evidence suggests a long-term health risk of cesarean section for the mother and child, but few studies have examined the link between cesarean section and parenting stress. Here, we examined this association by exploiting a large dataset.

Methods
Participants were 65,235 mothers participating in the Japan Environment and Children’s Study, an ongoing nationwide birth cohort. Outcome variables were parenting stress assessed as total score and subscale scores (representing the difficult child, parental distress, and spouse factors) on the Japanese 19-item version of the Parenting Stress Index Short Form (J-PSI-SF). Exposures were the mode of delivery, the timing of the J-PSI-SF assessment (1.5, 2.5, and 3.5 years postpartum), and the interaction between them. Multivariate regression analysis was used to calculate adjusted β coefficients and standard error of the means (SEMs).

Results
The J-PSI-SF total score was higher in the cesarean section group than in the vaginal delivery group (adjusted β = 0.24, SEM = 0.09). This increase was primarily due to higher scores for the difficult child factor (adjusted β = 0.18, SEM = 0.05) and not to higher scores for the parental distress or spouse factor.

Conclusions
Cesarean section was associated with higher parenting stress, especially in relation to the difficult child factor. Our results highlight the importance of paying particular attention to the mental health of both mother and child in the case of cesarean section.
Phase 2 multi-institutional prospective feasibility study of uracil-tegafur and leucovorin as adjuvant chemotherapy for patients aged 80 years or more after curative resection of colorectal cancer: The HiSCO-03 study.
Authors: Miguchi Masashi , Ikeda Satoshi , Shimomura Manabu , Nakahara Masahiro , Adachi Tomohiro , Ishizaki Yasuyo , Saitoh Yasufumi , Toyota Kazuhiro , Sumitani Daisuke , Shimizu Yosuke , Takakura Yuji , Shimizu Wataru , Yoshimitsu Masanori , Kodama Shinya , Fujimori Masahiko , Oeda Mamoru , Kobayashi Hironori , Ohdan Hideki 
Published: January 2023

101 Background: There is no consensus on the safety and effectiveness of adjuvant chemotherapy for patients with stage III colorectal cancer (CRC) aged ≥80 years who underwent curative resection. We conducted a prospective phase II feasibility study of uracil-tegafur and leucovorin (UFT/LV) as adjuvant chemotherapy in this population. Methods: This study involved 15 institutions of the Hiroshima Surgical Oncology Study Group (HiSCO). Patients with stage III CRC aged ≥80 years who underwent curative resection with an Eastern Cooperative Oncology Group performance status of 0–1 were enrolled. Eligible patients received UFT/LV therapy (UFT, 300 mg/m2 per day as tegafur; LV, 75 mg/day on days 1–28, every 35 days for five courses). Primary endpoint was feasibility, and secondary endpoints were safety and relative dose intensity. Results: Sixty-nine patients were enrolled in the study between December 2013 and June 2021. Of the 69 patients, 65 were included in the analysis, excluding two ineligible patients and two who discontinued before treatment commenced. There were 32 males and 33 females with a median age of 82 years (range, 80–88 years). There were four patients with stage IIIA CRC, 49 with stage IIIB, and 12 with stage IIIC. In the primary endpoint, administration completion rate was 67.3% (95% confidence interval: 54.9The median relative dose intensities were 84% (range, 4–100%) for UFT, and 100% (range, 4–100%) for LV. Incidence of grade three or higher adverse events were neutropenia (1.5%), aspartate transaminase elevation (3%), alanine transaminase elevation (1.5%), oral mucositis (3%), anemia (1.5%), and diarrhea (4.6%). No treatment-related deaths occurred. An independent risk factor was not identified in the background risk factor analysis for treatment discontinuation. Conclusions: Uracil-tegafur and leucovorin are not recommended as standard adjuvant therapy for patients with stage III CRC ≥80 years of age because of the possibility of lower completion rates. The frequency of serious adverse events was acceptable, and safety was confirmed in the treated patients. It is necessary to clarify the background of patients in which administration is discontinued and to investigate the impact on long-term prognosis. Clinical trial information: R000013902 .
A meta-analysis of bevacizumab’s cardiovascular risks in patients treated for colorectal cancer.
Authors: Chitkara Akshit , Desai Aditya , Mehta Devanshi , Kaur Nirmaljot , Anamika Fnu , Desai Darshi , Thawani Rajat 
Published: January 2023

113 Background: Bevacizumab (BVZ), a recombinant humanized monoclonal IgG antibody, is commonly used as first- and second-line adjuvant therapy in metastatic colorectal cancer. Recent guidelines have shown that a combination of three cytotoxic drug regimens FOLFOX (fluorouracil, leucovorin and oxaliplatin) along with BVZ is regarded as one of the first-line options. As we see an upward trend in using BVZ; it is crucial to analyze the side effects and potential toxicities. A frequent adverse effect with BVZ is hypertension. The prevailing hypothesis for the mechanism of BVZ induced hypertension is an increase in vascular tone due to the inhibition of VEGF-mediated vasodilation. A persistent elevation of arterial blood pressure is generally asymptomatic, but unmanaged hypertension can lead to cardiovascular complications, encephalopathy, and subarachnoid hemorrhage. Therefore, this meta-analysis aims to evaluate and assess the risk of BVZ induced hypertension. Methods: Our search included articles from PubMed, EMBASE, Web of Science, and Cochrane Library from 1980 to March 2022. Randomized controlled trials and clinical trials with BVZ as an add-on therapy mentioning cardiovascular side effects were included. Full analysis control group included various guideline directed chemotherapies and the subgroup analysis control group focused on FOLFOX therapy. A random-effects model was used with Review Manager, and a P value < 0.05 was considered significant. Results: We included a total of 17,807 patients in our study with an average age of 65 years. Analysis pooled from 19 RCTs showed that the odds of hypertension (Grade 3 or more) in patients treated with BVZ were about four times higher than the control group (OR 3.82, 95% CI 3.35-4.36, p-value < 0.00001, I2 = 78%). In a subgroup analysis, BVZ was compared with FOLFOX group, with odds of hypertension (Grade 3 or more) in BVZ group being about five times higher than in FOLFOX group (OR 5.24, 95% CI 4.06-6.77, p-value < 0.00001, I2 = 58%). Conclusions: Our meta-analysis demonstrates a significant cardiovascular risk of Bevacizumab when added to the standard regime for advanced colorectal cancer treatment. When BVZ was used as an add-on therapy to FOLFOX regimens for colorectal cancer, it was associated with about five times higher odds of developing hypertension (Grade 3 or more) in the treatment group with BVZ. Previous RCTs have demonstrated that BVZ add-on therapy to the standard regime is safe and without significant risk of toxicity. Our findings are important as they give vital information in assessing the risk-benefit ratio of adding BVZ, especially in a population with vascular comorbidities. Now that we have established the statistical significance of hypertensive risk with BVZ, it will be interesting to see how these events can be prevented in patients treated for metastatic colorectal cancer. Dedicated RCTs are needed to confirm these findings.
Multicenter retrospective study of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) for vulnerable patients with pretreated metastatic colorectal cancer (mCRC): WJOG14520G (TWILIGHT).
Authors: Mitani Seiichiro , Kito Yosuke , Kawakami Hisato , Nishina Shinichi , Matsumoto Toshihiko , Tsuzuki Takao , Shinohara Yudai , Shimokawa Hozumi , Kumanishi Ryosuke , Ohta Takashi , Kimura Shinya , Kawakami Takeshi , Nishina Tomohiro , Hasegawa Hiroko , Akiyoshi Kohei , Chiba Yasutaka , Yamazaki Kentaro , Hironaka Shuichi , Muro Kei 
Published: January 2023

121 Background: In the phase III SOLSTICE study, FTD/TPI plus BEV showed similar efficacy to capecitabine plus BEV as first-line treatment for patients with mCRC ineligible for full-dose combination chemotherapy with oxaliplatin [OX] or irinotecan [IRI] (intensive therapy). We evaluated clinical outcomes of FTD/TPI plus BEV as second- or later lines treatment for vulnerable patients, who were defined to be intolerant to intensive therapy. Methods: This was a multicenter retrospective study of vulnerable patients with unresectable mCRC who received FTD/TPI plus BEV as second- or later lines treatment between May 2014 and October 2020. Main eligibility criteria were histologically proven adenocarcinoma, ECOG PS 0-2, prior chemotherapy for unresectable disease, considered intolerant to intensive therapy, and underwent FTD/TPI plus BEV without prior exposure to at least one key cytotoxic agent (fluoropyrimidines [FP], OX, or IRI). Results: Of 96 patients enrolled from 26 Japanese hospitals, 93 patients were evaluable. Patient characteristics were as follows: median age, 79 years (range 21-90); male, 53%; ECOG PS 0-1, 89%; right-sided primary tumor, 30%; primary tumor resection, 86%; RAS mutant, 63%; BRAF mutant, 1%; second-line treatment, 80%; prior exposure to FP 100%, OX 50%, and IRI 15%. Main reasons for intolerance to intensive therapy were older age (65%), poor PS (20%), and renal failure (5%). Initial dose of FTD/TPI was reduced in 30 (32%) patients. The response rate was 5% and disease control rate was 68%. With median follow-up of 21.6 months, the median progression-free survival, time to treatment failure, and overall survival were 6.3, 4.5, and 18.6 months, respectively. Major grade >3 adverse events were neutropenia (54%), anemia (20%), thrombocytopenia (9%), hypertension (7%), and febrile neutropenia (2%). No treatment-related deaths were observed. The treatment was discontinued in 89 patients due to disease progression (n = 72), patient’s refusal (n = 10), and adverse events (n = 6). After FTD/TPI plus BEV, chemotherapies such as regimens including IRI or OX (n = 20), regorafenib (n = 16), and anti-EGFR antibody monotherapy (n = 7) were performed in 42 patients. Conclusions: FTD/TPI plus BEV as second- or later lines treatment for vulnerable patients with mCRC showed promising clinical activity and acceptable safety profile. This study suggested that FTD/TPI plus BEV could be a treatment option for vulnerable patients with pretreated mCRC. Clinical trial information: UMIN000044136 .
Colorectal endoscopic submucosal dissection using a concealable robotic add-on device: A comparative in vivo feasibility study.
Authors: Kim Sang Hyun , Keum Bora , Choi Hyuk Soon , Jeen Yoon Tae , Chun Hoon Jai , Hong Daehie 
Published: January 2023

128 Background: Appropriate tissue tension and clear visibility of the dissection area using traction are essential for effective and safe colonic endoscopic submucosal dissection (ESD). In this preclinical ex vivo and in vivo animal study, we developed a concealable robotic-assisted traction device and evaluated its performance in colorectal ESD. Methods: An experienced endoscopist performed ESD on an ex vivo porcine colon 18 times using our robot and 18 times using the conventional method. The outcome measures were procedure time, dissection speed, procedure-related adverse events, and blind dissection rate. We also conducted an in vivo feasibility study in live pigs. Robotic ESD was performed by experienced and novice endoscopist groups (n = 2, each). The outcomes included time to complete each ESD step, total procedure time, size of the dissected mucosa, rate of en bloc resection, and major adverse events. Results: Thirty-six colonic lesions were resected from ex vivo porcine colon samples. The total procedure time was significantly shorter in robotic ESD (RESD) than in conventional ESD (CESD) (20.1±4.1 vs. 34.3±8.3; P < 0.05). The submucosal dissection speed was significantly higher in the RESD group than in the CESD group (36.8±9.2 vs. 18.1±4.7; P < 0.05). The blind dissection rate was also significantly lower in the robotic group (12.8±3.4% vs. 35.1±3.9%; P < 0.05). In an in vivo feasibility study, the robot was attached to the colonoscope and successfully inserted into the proximal colon without damaging the colonic wall, and ESD was successfully performed. There was no significant difference in the submucosal dissection speed between the groups (P = 0.465). Conclusions: When the concealable robot assisted the colonic ESD procedure, the dissection speed and safety profile improved significantly. Thus, our robotic device can provide a simple, effective, and safe multidirectional traction during colonic ESD. When the robot was assisting in the ESD procedure, the dissection speed improved significantly, especially in the novice endoscopists.
Panitumumab plus trifluridine/tipiracil as third-line anti-EGFR rechallenge therapy in chemo-refractory RAS WT metastatic colorectal cancer: The VELO randomized phase II clinical trial.
Authors: Napolitano Stefania , De Falco Vincenzo , Martini Giulia , Esposito Lucia , Famiglietti Vincenzo , Martinelli Erika , Ciardiello Davide , Marrone Francesca , Avallone Antonio , Cardone Claudia , De Stefano Alfonso , Montesarchio Vincenzo , Zampino M. Giulia , Bordonaro Roberto , Scartozzi Mario , Santini Daniele , Di Maio Massimo , Ciardiello Fortunato , Troiani Teresa 
Published: January 2023

129 Background: Rechallenge therapy with epidermal growth factor receptor (EGFR) inhibitors in chemo-refractory metastatic colorectal cancer (mCRC) is an emerging therapeutic approach. Trifluridine-tipiracil is approved for treatment of chemo-refractory mCRC patients. Methods: Chemo-refractory RAS WT mCRC patients, that had a major response (partial or complete response) to first-line chemotherapy plus an anti-EGFR monoclonal antibody and had an-anti-EGFR drug-free interval during second-line therapy of four or more months were randomized in a phase II trial to assess the addition of the anti-EGFR monoclonal antibody panitumumab to trifluridine-tipiracil as third-line rechallenge therapy. The primary endpoint was progression free survival (PFS). Baseline plasma was analyzed for circulating free tumor (ct) DNA by using Biocartis Idylla platform to detect mutations in KRAS, NRAS, BRAF ( V600E) and EGFRextracellular domain ( S492R). In 24 patients with baseline RAS/BRAF wild type (WT) ctDNA, Foundation One liquid CDx (324 gene profiling) was also performed before treatment and at disease progression. Results: 62 patients were treated with trifluridine-tipiracil (31 patients, arm A) or with trifluridine-tipiracil plus panitumumab (31 patients, arm B). As of September 16, 2022, 1 patient in arm A and 2 patients in arm B were on treatment. The primary endpoint was met. Median PFS (mPFS) was 4 months in arm B versus 2.5 months in arm A [hazard ratio (HR): 0.48; 95% CI 0.28-0.82; P = 0.007]. Baseline plasma RAS/BRAF WT ctDNA was found in 23/31 patients in Arm A and in 26/31 patients in Arm B. In this group, mPFS was 4.5 months in Arm B versus 2.6 months in Arm A (HR: 0.48; 95% CI 0.26-0.89; P = 0.019). Disease control (major responses plus stable disease) was higher for patients in Arm B compared to Arm A (81% versus 48%), whereas disease progression was the best response in 19% versus 52% patients, respectively. PFS rates at 6 and 12 months were 38.5% and 15.4% in arm B versus 13% and 0% in arm A. At disease progression, Foundation One liquid CDx detected several mutations within the EGFR pathway, which could correlate with cancer cell resistance to panitumumab. Conclusions: This is the first prospective randomized trial which evaluated anti-EGFR monoclonal antibody (panitumumab) in addition to standard of care (trifluridine-tipiracil) as third-line rechallenge therapy in chemo-refractory RASWT mCRC patients. Baseline liquid biopsy allows selection of RAS/BRAF WT ctDNA patients who could have a relevant clinical benefit. Clinical trial information: NCT05468892 .