bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prophylactic Use of Antifibrinolytics During Pediatric Cardiac Surgery With Cardiopulmonary Bypass on Postoperative Bleeding and Transfusion: A Systematic Review and Meta-Analysis
Authors: Schertz Katherine , Karam Oliver , Demetres Michelle , Mayadunna Samantha , Faraoni David , Nellis Marianne E. 
Published: August 2022

Objectives:
To determine the effect of intraoperative antifibrinolytics, including tranexamic acid (TXA), aminocaproic acid (EACA), or aprotinin, on bleeding in children undergoing cardiac surgery with cardiopulmonary bypass (CPB).

Data Sources:
Relevant articles were systematically searched from Ovid MEDLINE, Ovid EMBASE, CINAHL, Cochrane Library, and Web of Science to November 15, 2021.

Study Selection:
Abstracts were screened, and full texts were reviewed using predetermined inclusion and exclusion criteria using the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline.

Data Extraction:
A standardized data extraction tool was used.

Data Synthesis:
Sixty-eight studies including 28,735 patients were analyzed. TXA compared with placebo resulted in a mean decrease in chest tube output of 9.1 mL/kg (95% CI, 6.0–12.3 mL/kg), I
2 equals to 65.2%, p value of less than 0.001, platelet requirement of 2.9 mL/kg (95% CI, 0.1–5.8 mL/kg), I
2=72.5%, p value less than 0.001 and plasma requirement of 4.0 mL/kg (95% CI, 0.6–7.2 mL/kg), I
2 equals to 94.5%, p value less than0.001. Aprotinin compared with placebo resulted in a mean decrease in chest tube output of 4.3 mL/kg (2.4–6.2 mL/kg), I
2 equals to 66.3%, p value of less than 0.001, platelet transfusion of 4.6 mL/kg (95% CI, 0.6–8.6 mL/kg), I
2 equals to 93.6%, p value of less than 0.001, and plasma transfusion of 7.7 mL/kg (95% CI, 2.1–13.2 mL/kg), I
2 equals to 95.3%, p value of less than 0.001. EACA compared with placebo resulted in a mean decrease in chest tube output of 9.2 mL/kg (2.3–21.0 mL/kg), I
2 equals to 96.4%, p value of less than 0.001, RBC transfusion of 7.2 mL/kg (95% CI, 2.4–12.1 mL/kg), I
2 equals to 94.5%, p value equals to 0.002, and platelet transfusion of 10.7 mL/kg (95% CI, 2.9–18.5 mL/kg), I
2 equals to 0%, p value of less than 0.001. No statistical difference was observed in chest tube output when TXA was compared with aprotinin. Subgroup analysis of cyanotic patients showed a significant decrease in chest tube output, platelet requirement, and plasma requirement for patients receiving aprotinin. Overall, the quality of evidence was moderate.

Conclusions:
Antifibrinolytics are effective at decreasing blood loss and blood product requirement in children undergoing cardiac surgery with CPB although the quality of evidence is only moderate.
Prolonged Mechanical Ventilation in Pediatric Trauma Patients in a Combat Zone
Authors: Moulton Andrew W. , Schauer Steven G. , Borgman Matthew A. 
Published: August 2022

OBJECTIVES:
It is well known that polytrauma can lead to acute lung injury. Respiratory failure has been previously observed in combat trauma, but not reported in children, who account for over 11% of bed days at deployed Military Treatment Facilities (MTFs) using significant resources. We seek to identify risk factors associated with prolonged mechanical ventilation (PMV) which is important in resource planning and allocation in austere environments.

DESIGN:
Retrospective review of prospectively collected data within the United States Department of Defense Trauma Registry.

SETTING:
Deployed U.S. MTFs in Iraq and Afghanistan from 2007 to 2016.

PATIENTS:
All pediatric subjects who required at least 1 day of mechanical ventilation, excluding patients who died on day 0.

INTERVENTIONS:
PMV was defined using the Youden index for mortality. A multivariable logistic regression model was then performed to identify factors associated with PMV.

MEASUREMENTS AND MAIN RESULTS:
The Youden index identified greater than or equal to 6 days as the cutoff for PMV. Of the 859 casualties included in the analysis, 154 (17.9%) had PMV. On univariable analysis, age, severe injury to the thorax and skin, 24-hour volume/kg administration of crystalloids, colloids, platelets, plasma, and packed RBCs was associated with PMV. In the multivariable model, odds ratios (95% CI) associated with PMV were crystalloids 1.04 (1.02–1.07), colloids 1.24 (1.04–1.49), platelets 1.03 (1.01–1.05), severe injury to the thorax 2.24 (1.41–3.48), and severe injury to the skin 4.48 (2.72–7.38). Model goodness-of-fit r
2 was 0.14.

CONCLUSIONS:
In this analysis of factors associated with PMV in pediatric trauma patients in a combat zone, in addition to severe injury to skin and thorax, we found that administration of crystalloids, colloids, and platelets was independently associated with greater odds of PMV. Our findings will help inform resource planning and suggest potential resuscitation strategies for future studies.
Using the Random Forest Algorithm to Detect the Activity of Graves Orbitopathy
Authors: Wang Minghui , Zhang Hanqiao , Dong Li , Li Yang , Hou Zhijia , Li Dongmei 
Published: August 2022

Purpose:
The aim of this study is to establish a random forest model to detect active and quiescent phases of patients with Graves Orbitopathy (GO).

Methods:
A total of 243 patients (486 eyes) diagnosed with GO in Beijing TongRen hospital were included in the study. The Clinical Activity Score of GO was regarded as the golden standard, whereas sex, age, smoking status, radioactive I131 treatment history, thyroid nodules, thyromegaly, thyroid hormone, and Thyroid-stimulating hormone receptor antibodies were chosen as predictive characteristic variables in the model. The random forest model was established and compared with logistic regression analysis, Naive Bayes, and Support vector machine metrics.

Results:
Our model has a sensitivity of 0.81, a specificity of 0.90, a positive predictive value of 0.87, a negative predictive value of 0.86, an F1 score of 0.85, and an out-of-bag error of 0.15. The random forest algorithm showed a more precise performance compared with 3 other models based on the area under receiver operating characteristic curve (0.92 versus 0.77 versus 0.76 versus 0.75) and accuracy (0.86 versus 0.71 versus 0.69 versus 0.66).

Conclusions:
By integrating these high-risk factors, the random forest algorithm may be used as a complementary method to determine the activity of GO, with accurate and reliable performance.
Differences Between Impression Stone Pouring and Digital Pouring in Fully Guided Dental Implant Surgery: A Prospective Clinical Study
Authors: Anssari Hussein B. , AL-Anee Auday M. 
Published: August 2022

Modern clinical protocols in implantology aim to reduce the duration and discomfort of the surgical phase while preserving excellent treatment results. The purpose of this study is to evaluate the clinical differences between impression stone pouring and impression digital pouring required for surgical guide fabrication in fully guided dental implant surgery. This study was conducted for partially edentulous patients with straightforward cases who did not require bone or soft tissue augmentation. Forty dental implants were installed in 14 patients (age range: 25–70 y) at the Dental Implant Unit, Oral and Maxillofacial Surgery Center, Gazi Alhariri Teaching Hospital, Medical City, Baghdad. The dental implants were guided into the most prosthetically suitable position using a surgical guide. Twenty of them were guided by conventional impression stone pouring to create the surgical guide, whereas the other 20 implants were installed using digital pouring for the dental impression to fabricate the surgical guide. The mean for impression stone pouring in regard to angular deviation of 4.33±3.435 degree, the depth difference was 1.29±0.90 mm and entry point deviation 0.99±0.84 mm. In contrast, the mean for digital pouring in regard to angular deviation of 3.34±2.10 degree, depth difference was 0.89±0.67 mm and entry point deviation was 0.83±0.61 mm. This study revealed that there was no significant difference between the 2 groups regarding all 3 variables at a P-value of 0.05. Neither biological nor mechanical complications occurred.
Adjuvant Therapy After Neoadjuvant Therapy for Esophageal Cancer
Authors: Raja Siva , Rice Thomas W. , Lu Min , Semple Marie E. , Blackstone Eugene H. , Murthy Sudish C. , Ahmad Usman , McNamara Michael , Toth Andrew J. , Ishwaran Hemant ,   for the Worldwide Esophageal Cancer Collaboration Investigators
Published: August 2022

Objective:
We hypothesized that, on average, patients do not benefit from additional adjuvant therapy after neoadjuvant therapy for locally advanced esophageal cancer, although subsets of patients might. Therefore, we sought to identify profiles of patients predicted to receive the most survival benefit or greatest detriment from adding adjuvant therapy.

Background:
Although neoadjuvant therapy has become the treatment of choice for locally advanced esophageal cancer, the value of adding adjuvant therapy is unknown.

Methods:
From 1970 to 2014, 22,123 patients were treated for esophageal cancer at 33 centers on 6 continents (Worldwide Esophageal Cancer Collaboration), of whom 7731 with adenocarcinoma or squamous cell carcinoma received neoadjuvant therapy; 1348 received additional adjuvant therapy. Random forests for survival and virtual-twin analyses were performed for all-cause mortality.

Results:
Patients received a small survival benefit from adjuvant therapy (3.2±10 months over the subsequent 10 years for adenocarcinoma, 1.8±11 for squamous cell carcinoma). Consistent benefit occurred in ypT3–4 patients without nodal involvement and those with ypN2–3 disease. The small subset of patients receiving most benefit had high nodal burden, ypT4, and positive margins. Patients with ypT1–2N0 cancers had either no benefit or a detriment in survival.

Conclusions:
Adjuvant therapy after neoadjuvant therapy has value primarily for patients with more advanced esophageal cancer. Because the benefit is often small, patients considering adjuvant therapy should be counseled on benefits versus morbidity. In addition, given that the overall benefit was meaningful in a small number of patients, emerging modalities such as immunotherapy may hold more promise in the adjuvant setting.
The physiology of failure: Identifying risk factors for mortality in emergency general surgery patients using a regional health system integrated electronic medical record
Authors: Baimas-George Maria , Ross Samuel W. , Hetherington Timothy , Kowalkowski Marc , Wang Huaping , Thompson Kyle , Cunningham Kyle , Matthews Brent D. , May Addison K. , Reinke Caroline E. 
Published: August 2022

BACKGROUND
Emergency general surgery (EGS) patients have increased mortality risk compared with elective counterparts. Recent studies on risk factors have largely used national data sets limited to administrative data. Our aim was to examine risk factors in an integrated regional health system EGS database, including clinical and administrative data, hypothesizing that this novel process would identify clinical variables as important risk factors for mortality.

METHODS
Our nine-hospital health system's billing data were queried for EGS International Classification of Disease codes between 2013 and 2018. Codes were grouped by diagnosis, and urgent or emergent encounters were included and merged with electronic medical record clinical data. Outcomes assessed were inpatient and 1-year mortality. Standard and multivariable statistics evaluated factors associated with mortality.

RESULTS
There were 253,331 EGS admissions with 3.6% inpatient mortality rate. Patients who suffered inpatient and 1-year mortality were older, more likely to be underweight, and have neutropenia or elevated lactate. On multivariable analysis for inpatient mortality: age (odds ratio [OR], 1.7–6.7), underweight body mass index (OR, 1.6), transfer admission (OR, 1.8), leukopenia (OR, 2.0), elevated lactate (OR, 1.8), and ventilator requirement (OR, 7.1) remained associated with increased risk. Adjusted analysis for 1-year mortality demonstrated similar findings, with highest risk associated with older age (OR, 2.8–14.6), underweight body mass index (OR, 2.3), neutropenia (OR, 2.0), and tachycardia (OR, 1.7).

CONCLUSION
After controlling for patient and disease characteristics available in administrative databases, clinical variables remained significantly associated with mortality. This novel yet simple process allows for easy identification of clinical data points imperative to the study of EGS diagnoses that are critical in understanding factors that impact mortality.

LEVEL OF EVIDENCE
Prognostic and Epidemiologic; Level III.
Outcomes of Sorafenib for Recurrent Hepatocellular Carcinoma After Liver Transplantation in the Era of Combined and Sequential Treatments
Authors: Tovoli Francesco , Pallotta Dante Pio , Sansone Vito , Iavarone Massimo , De Giorgio Massimo , Ielasi Luca , Di Costanzo Giovan Giuseppe , Giuffrida Paolo , Sacco Rodolfo , Pressiani Tiziana , Di Donato Maria Francesca , Trevisani Franco , Fagiuoli Stefano , Piscaglia Fabio , Granito Alessandro 
Published: August 2022

Background.
Sorafenib and other tyrosine kinase inhibitors are the current standard of care for hepatocellular carcinoma (HCC) recurring after liver transplantation (LT). Sorafenib is sometimes regarded as a scarcely effective treatment in this setting because of some studies showing a short overall survival (OS) indirectly compared with historical series of nontransplanted patients. Additional data from multicenter prospective studies are needed before drawing definite conclusions.

Methods.
Retrospective analyses of a large prospective multicenter dataset of sorafenib-treated HCC patients to report the characteristics and outcomes of LT recipients (n = 81).

Results.
At the baseline, LT patients had key prognostic features (high prevalence of metastatic disease, and low prevalence of macrovascular invasion, α-fetoprotein >400 ng/mL, ALBI grade >1, performance status >0) that differentiated them from the typical populations of non-LT patient reported in clinical trials and observational studies. Moreover, a relevant proportion of LT patients received concurrent locoregional (12.3%) and postprogression systemic treatments (34.2%), resulting in a median OS of 18.7 mo.

Conclusions.
Multimodal and sequential treatments are relatively frequent in post-LT HCC patients and contribute to a remarkable OS, together with favorable baseline characteristics. Despite the impossibility of matching with non-LT patients, our results indirectly suggest that the metastatic nature of post-LT recurrence and concurrent antirejection regimens should not discourage systemic treatments.
Rare variants found in clinical gene panels illuminate the genetic and allelic architecture of orofacial clefting
Authors: Diaz Perez Kimberly K. , Curtis Sarah W. , Sanchis-Juan Alba , Zhao Xuefang , Head Taylor , Ho Samantha , Carter Bridget , McHenry Toby , Bishop Madison R. , Valencia-Ramirez Luz Consuelo , Restrepo Claudia , Hecht Jacqueline T. , Uribe Lina Moreno , Wehby George , Weinberg Seth M. , Beaty Terri H. , Murray Jeffrey C. , Feingold Eleanor , Marazita Mary L. , Cutler David J. , Epstein Michael P. , Brand Harrison , Leslie Elizabeth J. 
Published: August 2022

ABSTRACTPurposeOrofacial clefts (OFCs) are common birth defects including cleft lip (CL), cleft lip and palate (CLP), and cleft palate (CP). OFCs have heterogeneous etiologies, complicating clinical diagnostics as it is not always apparent if the cause is Mendelian, environmental, or multifactorial. Sequencing is not currently performed for isolated or sporadic OFCs, so we estimated the diagnostic yield for 418 genes in 841 cases and 294 controls.MethodsWe evaluated 418 genes using genome sequencing and curated variants to assess their pathogenicity using American College of Medical Genetics criteria.Results9.04% of cases and 1.02% of controls had ‘likely pathogenic’ (LP) variants (p<0.0001), which was almost exclusively driven by heterozygous variants in autosomal genes. CP (17.6%) and CLP (9.09%) cases had the highest yield while CL cases had a 2.80% yield. Out of 39 genes with LP variants, nine genes, includingCTNND1andIRF6, accounted for more than half of the yield (4.64% of cases). Most variants (61.8%) were ‘variants of uncertain significance’ (VUSs), occurring more frequently in cases (p=0.004), but no individual gene showed a significant excess of VUSs.ConclusionThese results underscore the etiological heterogeneity of OFCs and suggest sequencing could reduce the diagnostic gap in OFCs.
Nation-wide participation in FIT-based colorectal cancer screening in Denmark during the COVID-19 pandemic: An observational study
Authors: Olesen Tina Bech , Jensen Henry , Møller Henrik , Jensen Jens Winther , Andersen Berit , Rasmussen Morten 
Published: August 2022

AbstractBackgroundWorldwide, most colorectal cancer screening programmes were paused at the start of the COVID-19 pandemic, whilst the Danish faecal immunochemical test (FIT)-based programme continued without pausing. We examined colorectal cancer screening participation and compliance with subsequent colonoscopy in Denmark throughout the pandemic.MethodsWe used data from the Danish Colorectal Cancer Screening Database among individuals aged 50-74 years old invited to participate in colorectal cancer screening from 2018-2021 combined with population-wide registries. Using a generalised linear model, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) of colorectal cancer screening participation within 90 days since invitation and compliance with colonoscopy within 60 days since a positive FIT test during the pandemic in comparison with the previous years adjusting for age, month and year of invitation.ResultsAltogether, 3,133,947 invitations were sent out to 1,928,725 individuals and there were 94,373 positive FIT tests (in 92,848 individuals) during the study period. Before the pandemic, 60.7% participated in screening within 90 days. A minor reduction in participation was observed at the start of the pandemic (PR=0.95; 95% CI: 0.94-0.96 in pre-lockdown and PR=0.85; 95% CI: 0.85-0.86 in 1stlockdown) corresponding to a participation rate of 54.9% during pre-lockdown and 53.0% during 1st lockdown. This was followed by a 5-10% increased participation in screening corresponding to a participation rate of up to 64.9%. The largest increase in participation was observed among 55-59 year olds, individuals living alone or cohabiting and immigrants. The compliance with colonoscopy within 60 days was 89.9% before the pandemic. A slight reduction was observed during 1stlockdown (PR=0.96; 95% CI: 0.93-0.98), where after it resumed to normal levels.ConclusionsParticipation in the Danish FIT-based colorectal cancer screening programme and subsequent compliance to colonoscopy after a positive FIT result was only slightly affected by the COVID-19 pandemic.FundingThe study was funded by the Danish Cancer Society Scientific Committee (grant number R321-A17417) and the Danish regions.
Csb1 moonlighting gives rise to functional redundancy with Csb2 in processing the pre-CRISPR transcript in type I-G CRISPR-Cas system
Authors: Chhetry Sunanda , Anand B 
Published: August 2022

AbstractArchaea and bacteria use CRISPR-based adaptive immunity to limit the genome invasion by phages. Among the type-I CRISPR variant, the newly discovered type I-G exhibits unusual variation in the composition and architecture of Cas proteins. In order to understand how these structural differences, contribute to functional adaptations, we probed how the maturation of CRISPR RNA differs with respect to other well studied type I CRISPR variants. Type I-G consists of three Cas proteins, viz, Csb1, Csb2 and Csb3 that are predicted to form the ribonucleoprotein surveillance effector complex. We show that Csb2 from Bifidobacterium animalis is a metal independent endonuclease that cleaves site-specifically within the 5’ region of the CRISPR repeat RNA. The catalytic activity resides within the C-terminal region that is homologous to Cas6. Interestingly, Csb2 processes the pre-CRISPR transcript both as a stand-alone enzyme and as a subunit of the Cascade/I-G complex that comprises of Csb1, Csb2 and Csb3 in association with crRNA. Surprisingly, we discovered that Csb1-which is homologous to Cas7 that is catalytically inert in other type I systems-also shows metal independent RNase activity that is functionally analogous to Csb2 in processing the pre-CRISPR RNA. The presence of dual nucleases in the Cascade/I-G complex enhances the efficiency of CRISPR-based immunity. We suggest that the Csb1 moonlighting engenders functional redundancy between Csb1 and Csb2 that in turn could compensate for the intrinsic instability of Csb2 and accelerate the maturation of crRNA.
Rapastinel Accelerates Loss of Withdrawal Signs after Repeated Morphine and Blunts Relapse to Conditioned Place Preference
Authors: Armstrong Christopher , Ferrante Julia , Lamichhane Nidesh , Gamard C , Reavis Zachery , Walker Q.D. , Zucker N , Patkar A , Kuhn Cynthia 
Published: August 2022

AbstractThe purpose of the present study was to evaluate the efficacy of rapastinel, an allosteric modulator of NMDA receptor function, to accelerate the loss of opioid withdrawal symptoms and blunt or prevent relapse to morphine conditioned place preference (CPP) in rats. Two studies were conducted. In study 1, adult and adolescent male and female rats were treated with increasing doses of morphine (5 mg/kg, bid to 25 mg/kg bid) for 5 days. On day 6 animals were treated with naloxone (1 mg/kg) and withdrawal was assessed. They were then treated with saline or rapastinel (5 mg/kg) on days 6 and 8, and withdrawal assessed on day 9. Rapastinel treated animals exhibited significantly lower levels of withdrawal signs on day 9. No sex or age differences were observed. In Study 2, CPP for morphine was established in adult rats (males and females) by 4 daily pairings with saline and morphine (am/pm alternation). They were tested for CPP on day 5, and then treated with rapastinel (5 mg/kg) or saline daily on days 6-10 of extinction. On day 11 they received a final dose of rapastinel or saline followed by extinction. On day 12, animals received 1 mg/kg of morphine and were tested for relapse. Rapastinel did not affect extinction of CPP, but rapastinel-treated animals spent significantly less time in the previously morphine-paired side than saline-treated animals during the relapse trial. These findings of accelerated loss of withdrawal signs and blunted relapse to CPP suggest that rapastinel could provide an adjunctive therapy for opioid dependence during initiation of pharmacotherapy for opioid dependence.