bluuebunny/crossref_metadata_2025_split huggingface dataset:
MRI-Based Pancreatic Atrophy Is Associated With Malignancy or Invasive Carcinoma in Intraductal Papillary Mucinous Neoplasm
Authors: Lin Tingting , Chen Xin , Liu Jingjing , Cao Yingying , Cui Wenjing , Wang Zhongqiu , Wang Cheng , Chen Xiao 
Published: June 2022

BackgroundAbrupt change in the caliber of the main pancreatic duct (MPD) with distal pancreatic atrophy (PA) was considered as one of worrisome features in the International Association of Pancreatology guideline and American College of Gastroenterology guideline for the management of intraductal papillary mucinous neoplasms (IPMNs). However, this feature was not included in other guidelines. Moreover, the association between PA alone and malignancy in IPMNs has not been fully evaluated. In the present study, we investigated the role of image-based PA in identifying malignant IPMNs or invasive carcinoma.MethodsA total of 186 patients with IPMNs were included for analysis. The tumor size, location, MPD diameter, presence of a mural nodule (MN), and PA were evaluated using magnetic resonance imaging. Demographic information and serum carbohydrate antigen 19-9 and carcinoembryonic antigen (CEA) levels were also collected. IPMNs with high-grade dysplasia and associated invasive carcinoma were regarded as malignant IPMNs.ResultsPA was observed in 34 cases (18.3%). The occurrence of malignant IPMNs or invasive carcinoma in patients with PA were significantly higher than in those without PA (52.9% vs. 22.3%; 44.1% vs. 8.9%, all P &lt; 0.01). Multivariate logistic regression analysis showed that PA was an independently associated factor for malignant IPMNs [odds ratio (OR) = 2.69, 95% confidence interval (CI): 1.07-6.78] or invasive carcinoma (OR = 7.78, 95%CI: 2.62-23.10) after modified with confounders. Subgroup analysis in MPD-involved IPMNs also indicated that PA was an independently associated factor for invasive carcinoma (OR = 9.72, 95%CI: 2.43-38.88). PA had a similar performance with MPD plus MN [the area under the curve (AUC) was both 0.71] in identifying malignancy. PA had a higher performance in identifying invasive carcinoma in MPD-involved IPMNs than MN (AUC = 0.71 vs. 0.65, P = 0.02).ConclusionOur data showed that imaging-based PA was associated with malignancy or invasive carcinoma regardless of abrupt change in the caliber of MPD in IPMNs. PA had an acceptable performance in identifying malignant IPMNs.
Prognostic Significance of NLR, PLR, LMR and Tumor Infiltrating T Lymphocytes in Patients Undergoing Surgical Resection for Hilar Cholangiocarcinoma
Authors: Lin Zhi-qiang , Ma Chi , Cao Wen-zhuo , Ning Zhen , Tan Guang 
Published: June 2022

ObjectiveThis study evaluated the prognostic significance of preoperative neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR) and tumor-infiltrating lymphocytes (TILs), and whether these preoperative blood inflammatory indicators were associated with TILs in hilar cholangiocarcinoma (HCCA).MethodsA total of 76 patients with HCCA who underwent radical resection were included. Data on their clinicopathologic characteristics, perioperative features, and survival outcomes were analyzed. The optimal cutoff levels for the NLR, PLR and LMR were defined by using the web application Cut-off Finder. The densities of specific immune cells (CD3+, CD4+, CD8+) within the tumor microenvironment were examined by immunohistochemical. The association of the number of CD3+, CD4+ and CD8+ T cells infiltration in the local tumor microenvironment with preoperative NLR, PLR and LMR level was analyzed. Survival curves were calculated using the Kaplan–Meier estimate. Univariate and multivariate logistic regression models were used to identify factors associated with overall survival.ResultsThe optimal cutoff value of preoperative NLR, PLR and LMR was 2.00, 117.60, and 4.02, respectively. NLR was significantly negatively correlated with CD3+ and CD8+ T cell infiltration, but not with CD4+ T cells. PLR had no correlation with CD3+, CD4+, or CD8+ T cell infiltration, while LMR had a significantly positive correlation with CD3+ T cells infiltration but not with CD4+ or CD8+ T cells. In the multivariate logistic regression model, T stage, lymph node metastasis, CA19-9 and LMR were independent risk factors associated with overall survival (OS). Survival curves indicated that HCCA patients with low CD3+ T cells infiltration and low preoperative LMR live shorter than others.ConclusionsLMR played as an independent factor for predicting the survival in patients with HCCA after R0 radical resection. A high LMR was associated with an accumulation of CD3+ T cells in HCCA.
Intensity-Modulated Radiotherapy Associated With Improved Survival Outcome in Anal Cancer
Authors: Mohamed Ahmed Allam , Schlenter Marsha , Heinzel Alexander , Kintsler Svetlana , Eble Michael J. 
Published: June 2022

PurposeTo describe the survival and toxicity outcome from a single-centre experience in patients with squamous cell cancer of the anal canal (SCC-AC), related to the impact of technological advances in diagnostics and radiation techniques.Material and MethodsA retrospective cohort study was performed after the approval of the institutional ethical committee (EK 478-21). We identified 142 patients in our registry, who received radical treatment for SCC-AC between 2000 and 2020. Fifty-five patients had FDG PET/CT for initial staging and target volume delineation, 87.33% received concomitant chemoradiotherapy (CRT), 64 patients were treated with 3-dimensional conformal radiotherapy (3DRT) between 2000-2009, and 78 patients with intensity-modulated radiotherapy (IMRT) between 2009-2020. Endpoints for the analysis included locoregional relapse-free survival (LRFS), disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS). Acute and late toxicities were also reported.ResultsAt a median follow-up of 31.2 months, the median overall survival was 135 months, 5-year LRFS was 73.1%, 5-year DFS was 65.3%, and 5-year CSS was 75.3%. The use of IMRT was associated with shorter treatment duration. In the univariate analysis, IMRT was associated with significantly improved DFS and CSS for the whole cohort and significantly improved DFS, OS, and CSS for patients who received CRT. In the multivariate analysis, IMRT was associated with the improvement of all survival paraments. The use of FDG PET/CT did not translate into an improvement in the survival outcomes in both univariate and multivariate analyses. Grade-3 and more dermatological toxicities occurred less frequently, but hematological toxicities were more frequent in the IMRT-group. Late side effects and colostomies were less frequently reported in the IMRT group.ConclusionThe use of IMRT in the management of SCC-AC was associated with improvement of the oncological outcomes with improved toxicity profiles in this long-term single-centre experience.
Glutathione Peroxidase 4 as a Therapeutic Target for Anti-Colorectal Cancer Drug-Tolerant Persister Cells
Authors: Zhang Xiaoli , Ma Yiming , Ma Jianhui , Yang Lan , Song Qingzhi , Wang Hongying , Lv Guoqing 
Published: June 2022

BackgroundDespite the effectiveness of chemotherapy and targeted therapy for colorectal cancer, drug resistance drives therapy failure and tumor relapse. Increasing evidence has suggested that cancer cells can enter a reversible drug-tolerant persister state to survive chemotherapy or targeted agents. However, the traits and treatable vulnerabilities of anti-colorectal cancer drug-tolerant persister cells is not yet known.MethodsIn this study, we established 5-fluorouracil and AZ628-tolerant persister cell models in two colorectal cancer cell lines, namely HCT116 and SW620, and revealed the characteristics of colorectal cancer persister cells by cell viability assay and flow cytometry. We investigated the efficacy and mechanism of ferroptosis inducers RSL3 and FIN56 on persister cells, which are glutathione peroxidase 4 inhibitors. In the xenograft mouse model, we further evaluated the inhibitory effect of RSL3 on tumor regrowth.ResultsColorectal cancer persister cells, which were enriched in the residual cancer cell population, exhibited reduced drug sensitivity, were largely quiescent and expressed high levels of stem cell-related genes and mesenchymal markers but not epithelial markers. The persister cells were more sensitive and underwent ferroptosis induced by glutathione peroxidase 4 inhibitors. Mechanistically, glutathione peroxidase 4 and ferrous iron, which are pivotal ferroptosis regulators, were upregulated in residual cells or tumors, and were hence potential therapeutic targets of persister cells. In the xenograft model, we confirmed that inhibition of glutathione peroxidase 4 restrained tumor regrowth after discontinuation of anti-cancer drug treatment. Moreover, biopsies obtained from patients with colorectal cancer undergoing neoadjuvant chemoradiotherapy revealed upregulated glutathione peroxidase 4 and ferritin heavy chain 1. High glutathione peroxidase 4 expression correlates with a worse prognosis in colorectal cancer patients.ConclusionsOur work reveals that the upregulated glutathione peroxidase 4 and ferrous iron in anti-colorectal cancer drug-tolerant persister cells were potential therapeutic targets. Glutathione peroxidase 4 inhibition combined with chemotherapy or targeted therapy may be a promising therapy for colorectal cancer.
Rapid-Onset Opioids for Management of Breakthrough Cancer Pain: Considerations for Daily Practice
Authors: Bossi Paolo , Escobar Yolanda , Pea Federico 
Published: June 2022

Background and ObjectiveRapid-onset opioids (ROOs) are effective treatments for breakthrough cancer pain (BTcP) given their rapid onset of action and relatively short duration of analgesia. The aim of this article is to describe specific considerations for the use of ROOs in daily practice, focusing on dose titration and treatment of specific populations.Type of ReviewWe conducted a narrative review on the use of ROOs for BTcP. We selected papers according to the following search terms: “breakthrough cancer pain” and “rapid onset opioids”.ResultsROOs may be considered as the most suitable drugs to treat BTcP and can be used “on-demand”. Several fentanyl formulations are available and have been associated with control of BTcP and with improvement in quality of life. Various titration schemes have been used to optimize ROO dosing; however, a dose-proportional scheme could be considered safe and effective in most patients. Specific formulations may be more suitable for specific patient subgroups; for example, patients with oral mucositis may prefer intranasal to oral formulations. Moreover, elderly patients or those without caregivers should be clearly educated on the use of these formulations. A key element in achieving successful treatment of BTcP is awareness of the barriers to pain management, including poor overall assessment, patient reluctance to take opioids or report pain, and physician reluctance to prescribe opioids.ConclusionA personalized approach is fundamental when prescribing a medication for BTcP, and careful attention should be given to drug choice and route of administration, and to the need for alternative therapeutic options.
Overweight/Obesity in Childhood and the Risk of Early Puberty: A Systematic Review and Meta-Analysis
Authors: Zhou Xuan , Hu Yang , Yang Ziqi , Gong Ziqiang , Zhang Senmao , Liu Xiaoling , Chen Yan , Ye Changxiang , Chen Lizhang , Wang Tingting 
Published: June 2022

PurposeTo determine the relationship between childhood overweight/obesity and early puberty in both boys and girls. Specifically, this is the first time to conduct a meta-analysis of the relationship between childhood overweight/obesity and early puberty in boys.MethodsRelevant studies were identified from PubMed, Web of Science, and EMBASE searches. The exposure of interest was overweight/obesity in childhood. Childhood was defined internationally as the age range of 0–18 years. The overall risk estimates were pooled using random effects models. Subgroup and sensitivity analyses were performed to explore possible sources of heterogeneity and to assess the robustness of the results.ResultsA total of 10 studies involving 13,338 girls and 12,796 boys were included. Results showed that childhood overweight/obesity were associated with a significantly higher risk of early puberty in girls [odds ratio (OR): 2.22, 95% CI: 1.65–2.99]. Although without statistical significance, a higher risk of early puberty was also found in boys who were overweight/obese in childhood (OR: 1.29, 95% CI: 0.98–1.70). Heterogeneity in the risk estimates of early puberty was partially explained by study design, sample size, follow-up duration, definitions of early puberty and confounders controlled. Sensitivity analyses validated the robustness of the findings.ConclusionsOur findings showed that for girls the associate between overweight/obesity and early puberty is definite or strong whereas for males, such an association is possible, prompting that future studies need to further explore the possible relationship between overweight/obesity and early puberty in boys.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021264649, PROSPERO CRD42021264649.
Contemporary Trends in Global Mortality of Sepsis Among Young Infants Less Than 90 Days: A Systematic Review and Meta-Analysis
Authors: Gan Ming Ying , Lee Wen Li , Yap Bei Jun , Seethor Shu Ting Tammie , Greenberg Rachel G. , Pek Jen Heng , Tan Bobby , Hornik Christoph Paul Vincent , Lee Jan Hau , Chong Shu-Ling 
Published: June 2022

ObjectiveCurrent knowledge on the global burden of infant sepsis is limited to population-level data. We aimed to summarize global case fatality rates (CFRs) of young infants with sepsis, stratified by gross national income (GNI) status and patient-level risk factors.MethodsWe performed a systematic review and meta-analysis on CFRs among young infants &lt; 90 days with sepsis. We searched PubMed, Cochrane Central, Embase, and Web of Science for studies published between January 2010 and September 2019. We obtained pooled CFRs estimates using the random effects model. We performed a univariate analysis at patient-level and a meta-regression to study the associations of gestational age, birth weight, onset of sepsis, GNI, age group and culture-proven sepsis with CFRs.ResultsThe search yielded 6314 publications, of which 240 studies (N= 437,796 patients) from 77 countries were included. Of 240 studies, 99 were conducted in high-income countries, 44 in upper-middle-income countries, 82 in lower-middle-income countries, 6 in low-income countries and 9 in multiple income-level countries. Overall pooled CFR was 18% (95% CI, 17–19%). The CFR was highest for low-income countries [25% (95% CI, 7–43%)], followed by lower-middle [25% (95% CI, 7–43%)], upper-middle [21% (95% CI, 18–24%)] and lowest for high-income countries [12% (95% CI, 11–13%)]. Factors associated with high CFRs included prematurity, low birth weight, age less than 28 days, early onset sepsis, hospital acquired infections and sepsis in middle- and low-income countries. Study setting in middle-income countries was an independent predictor of high CFRs. We found a widening disparity in CFRs between countries of different GNI over time.ConclusionYoung infant sepsis remains a major global health challenge. The widening disparity in young infant sepsis CFRs between GNI groups underscore the need to channel greater resources especially to the lower income regions.Systematic Review Registration[www.crd.york.ac.uk/prospero], identifier [CRD42020164321].
Nomograms for Predicting the Incidence of Late-Onset Acute Cellular Rejection in Patients After Pediatric Liver Transplantation
Authors: Si Zhuyuan , Dong Chong , Sun Chao , Wang Kai , Zhang Wei , Zheng Weiping , Wei Xinzhe , Gao Wei , Shen Zhongyang 
Published: June 2022

BackgroundLate-onset acute cellular rejection (LACR) is a special type of acute rejection (AR) only rarely studied after pediatric liver transplantation (pLT). Our study aimed to explore the influencing factors of LACR after pLT and establish a nomogram to provide an individualized prediction of LACR after pLT.Materials and MethodsData from 640 children who underwent pLT at Tianjin First Central Hospital from January 2016 to December 2019 were collected as part of this retrospective study. The nomogram was then established through the results of the multivariable analysis.ResultsForty-one patients experienced LACR &gt; 1 ≤ 2 years after pLT. Cold ischemia time, donor-specific antibodies (DSAs), and tacrolimus concentration were independent influencing factors, and a nomogram was established with an AUC value of 0.834 (95% confidence interval, 0.755–0.912). Ten-fold cross-validation showed that the accuracy of the nomogram was about 76%. Sixty-three patients experienced LACR &gt; 2 years after pLT. Child–Pugh grade, cold ischemic time, DSAs, early acute cellular rejection, and tacrolimus concentration were independent influencing factors, and a nomogram was established with an AUC value of 0.827 (95% confidence interval, 0.774–0.881). Ten-fold cross-validation showed that the accuracy of the nomogram was about 80.9%.ConclusionWe established nomograms to predict the incidence of LACR &gt; 1 ≤ 2 and &gt; 2 years after pLT, respectively. The verification results showed that nomograms had good accuracy and clinical practicability.
Update on Treatment of Infantile Hemangiomas: What’s New in the Last Five Years?
Authors: Macca Laura , Altavilla Domenica , Di Bartolomeo Luca , Irrera Natasha , Borgia Francesco , Li Pomi Federica , Vaccaro Federico , Squadrito Violetta , Squadrito Francesco , Vaccaro Mario 
Published: June 2022

Among benign vascular tumors of infancy, hemangiomas are the commonest, affecting approximately 5–10% of one-year-old children. They are derived from a benign proliferation of vascular endothelial cells (VECs) in the mesoderm and may arise anywhere on the body around 1–2 weeks after birth. Infantile hemangiomas (IHs) are characterized by an early proliferative phase in the first year followed by a spontaneous progressive regression within the following 5 years or longer. IH prevalence is estimated to be 5%–10% in one-year-old children and commonly affects female, Caucasian and low-birth weight infants. Although most of them spontaneously regress, approximately 10% requires treatment to prevent complications due to the site of occurrence such as bleeding, ulceration, cosmetically disfigurement, functional impairment, or life-threatening complications. For over 30 years, steroids have represented the first-line treatment for IHs, but recently topical or systemic β-blockers are increasingly being used and recognized as effective and safe. A search for “Cutaneous infantile hemangioma” [All Fields] AND “Treatment” [All Fields] was performed by using PubMed and EMBASE databases. Treatment of IHs with labeled drugs, such as oral propranolol, but also with off-label drugs, such as topical β-blockers, including topical timolol and carteolol, steroids, itraconazole or sirolimus, with a focus on formulations types and adverse events were described in our review. We also discussed the benefits of pulsed dye laser and the treatment of IHs with involvement of central nervous system, namely the PHACE and LUMBAR syndrome.
Benefits and Risks of Rapid Initiation of Antiretroviral Therapy: A Systematic Review and Meta-Analysis
Authors: Bai Ruojing , Du Juan , Lv Shiyun , Hua Wei , Dai Lili , Wu Hao 
Published: June 2022

Objectives: To compare the benefits and risks between Rapid ART and standard/delayed treatment for HIV.Methods: Databases of PubMed, Cochrane Library, Embase and Web of science were searched from the inception to 28 October 2021. Two investigators independently screened studies related to Rapid ART, extracted data, and evaluated the literature quality. The risk of bias was assessed by Cochrane Collaboration Risk of Bias Tool and the statistical software Stata15.0 was used for meta-analysis.Results: Ten eligible studies were included in this meta-analysis, the results showed Rapid ART was superior to standard/delayed treatment in continuing care for at least 8 months (RR = 1.13, 95%CI: 1.03∼1.25, Z = 2.44, p = 0.015), and severe bacterial infection (RR = 0.42, 95%CI: 0.25∼0.70, Z = 3.33, p = 0.001). At 12 months following treatment, there was no statistically significant difference in viral load &lt;100 copies/mL (RR = 1.05, 95%CI: 0.80∼1.39, Z = 0.35, p = 0.726), mortality (RR = 0.77, 95%CI: 0.47∼1.24, Z = 1.09, p = 0.277), or the incidence of adverse events (RR = 0.52, 95%CI: 0.16∼1.76, Z = 1.05, p = 0.294) compared with standard/delayed treatment.Conclusion: In comparison to standard/delayed treatment, rapid ART can reduce the incidence of TB and severe bacterial infections in HIV patients. Our findings suggest that rapid ART should be utilized when clinical conditions and the patient’s physical state allow.Systematic Review Registration: [https://inplasy.com/?s=202210004], identifier [INPLASY202210004].
CT Attenuation and Cross-Sectional Area of the Pectoralis Are Associated With Clinical Characteristics in Chronic Obstructive Pulmonary Disease Patients
Authors: Qiao Xin , Hou Gang , Kang Jian , Wang Qiu-Yue , Yin Yan 
Published: June 2022

Purpose:Muscle wasting is associated with prognosis in patients with chronic obstructive pulmonary disease (COPD). Computed tomography (CT) could serve as a method for muscle assessment due to its ability to measure both muscle quantity (e.g., cross-sectional muscle area) and muscle quality (e.g., muscle attenuation). Our study aimed to compare the differences in CT-derived pectoralis muscle cross-sectional area (PMA) and pectoralis muscle attenuation (PMT) between COPD patients and healthy controls and explore the association between PMA and PMT measurements and clinical characteristics in patients with COPD.Methods:A total of 252 participants included in our analysis consisted of 80 healthy controls and 172 patients with COPD. PMA and PMT were measured from a single axial slice of the CT scan above the aortic arch. Linear regression analysis was used to determine the correlation between PMA and PMT measurements and clinical characteristics in patients with COPD. Associations were adjusted for age, sex, BMI, FEV1%pred, smoking pack-years, current smoking status, emphysema percentage, and total airway count (TAC) of the right upper lobe apical bronchus (RB1).Results:PMA and PMT were lower in COPD patients, especially those with acute exacerbation, than in healthy controls. PMA and PMT were significantly associated with the severity of emphysema and the TAC of RB1 (p&lt; 0.05). Patients with stable COPD, who had lower PMA and lower PMT, had significantly worse pulmonary function, poorer exercise tolerance, decreased quality of life, and worse dyspnea scores. In addition, patients with acute COPD exacerbation, who had lower PMA and lower PMT, had a higher risk of respiratory failure on admission.Conclusion:CT-derived measurements of the pectoralis muscle may be helpful in detecting declines in muscle quantity and quality and predicting disease severity in patients with COPD.