Frontiers of Medicine

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Current applications of artificial intelligence for intraoperative decision support in surgery
Allison J. Navarrete-Welton, Daniel A. Hashimoto
Front. Med.    https://doi.org/10.1007/s11684-020-0784-7
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Research into medical artificial intelligence (AI) has made significant advances in recent years, including surgical applications. This scoping review investigated AI-based decision support systems targeted at the intraoperative phase of surgery and found a wide range of technological approaches applied across several surgical specialties. Within the twenty-one (n=21) included papers, three main categories of motivations were identified for developing such technologies: (1) augmenting the information available to surgeons, (2) accelerating intraoperative pathology, and (3) recommending surgical steps. While many of the proposals hold promise for improving patient outcomes, important methodological shortcomings were observed in most of the reviewed papers that made it difficult to assess the clinical significance of the reported performance statistics. Despite limitations, the current state of this field suggests that a number of opportunities exist for future researchers and clinicians to work on AI for surgical decision support with exciting implications for improving surgical care.

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Use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in context of COVID-19 outbreak: a retrospective analysis
Jiuyang Xu, Chaolin Huang, Guohui Fan, Zhibo Liu, Lianhan Shang, Fei Zhou, Yeming Wang, Jiapei Yu, Luning Yang, Ke Xie, Zhisheng Huang, Lixue Huang, Xiaoying Gu, Hui Li, Yi Zhang, Yimin Wang, Frederick G. Hayden, Peter W. Horby, Bin Cao, Chen Wang
Front. Med.    https://doi.org/10.1007/s11684-020-0800-y
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The possible effects of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on COVID-19 disease severity have generated considerable debate. We performed a single-center, retrospective analysis of hospitalized adult COVID-19 patients in Wuhan, China, who had definite clinical outcome (dead or discharged) by February 15, 2020. Patients on anti-hypertensive treatment with or without ACEI/ARB were compared on their clinical characteristics and outcomes. The medical records from 702 patients were screened. Among the 101 patients with a history of hypertension and taking at least one anti-hypertensive medication, 40 patients were receiving ACEI/ARB as part of their regimen, and 61 patients were on anti-hypertensive medication other than ACEI/ARB. We observed no statistically significant differences in percentages of in-hospital mortality (28% vs. 34%, P=0.46), ICU admission (20% vs. 28%, P=0.37) or invasive mechanical ventilation (18% vs. 26%, P=0.31) between patients with or without ACEI/ARB treatment. Further multivariable adjustment of age and gender did not provide evidence for a significant association between ACEI/ARB treatment and severe COVID-19 outcomes. Our findings confirm the lack of an association between chronic receipt of renin-angiotensin system antagonists and severe outcomes of COVID-19. Patients should continue previous anti-hypertensive therapy until further evidence is available.

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State-of-the-art of intelligent minimally invasive surgical robots
Masakatsu G. Fujie, Bo Zhang
Front. Med.    https://doi.org/10.1007/s11684-020-0743-3
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A number of developed countries are rapidly turning into super-aged societies. Consequently, the demand for reduced surgical invasiveness and enhanced efficiency in the medical field has increased due to the need to reduce the physical burden on older patients and shorten their recovery period. Intelligent surgical robot systems offer high precision, high safety, and reduced invasiveness. This paper presents a review of current intelligent surgical robot systems. The history of robots and three types of intelligent surgical robots are discussed. The problems with current surgical robot systems are then analyzed. Several aspects that should be considered in designing new surgical systems are discussed in detail. The paper ends with a summary of the work and a discussion of future prospects for surgical robot development.

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Human microbiome and prostate cancer development: current insights into the prevention and treatment
Solmaz Ohadian Moghadam, Seyed Ali Momeni
Front. Med.    https://doi.org/10.1007/s11684-019-0731-7
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The huge communities of microorganisms that symbiotically colonize humans are recognized as significant players in health and disease. The human microbiome may influence prostate cancer development. To date, several studies have focused on the effect of prostate infections as well as the composition of the human microbiome in relation to prostate cancer risk. Current studies suggest that the microbiota of men with prostate cancer significantly differs from that of healthy men, demonstrating that certain bacteria could be associated with cancer development as well as altered responses to treatment. In healthy individuals, the microbiome plays a crucial role in the maintenance of homeostasis of body metabolism. Dysbiosis may contribute to the emergence of health problems, including malignancy through affecting systemic immune responses and creating systemic inflammation, and changing serum hormone levels. In this review, we discuss recent data about how the microbes colonizing different parts of the human body including urinary tract, gastrointestinal tract, oral cavity, and skin might affect the risk of developing prostate cancer. Furthermore, we discuss strategies to target the microbiome for risk assessment, prevention, and treatment of prostate cancer.

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Analysis of antibiotic usage for viral community-acquired pneumonia in adults
Rongmeng Jiang, Bing Han, Chang Dou, Fei Zhou, Bin Cao, Xingwang Li
Front. Med.    https://doi.org/10.1007/s11684-019-0736-2
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The rationale for the antibiotic treatment of viral community-acquired pneumonia (CAP) in adults was analyzed to develop a clinical reference standard for this condition. Clinical data from 166 patients diagnosed with viral pneumonia across 14 hospitals in Beijing from November 2010 to December 2017 were collected. The indications for medications were evaluated, and the rationale for the use of antibiotics was analyzed. A total of 163 (98.3%) patients with viral pneumonia were treated with antibiotics. A combination of C-reactive protein (CRP) and procalcitonin (PCT) was used as markers to analyze the possible indications for antibiotic use. With threshold levels set at 0.25 µg/L for PCT and 20 mg/L for CRP, the rate of unreasonable use of antibiotics was 55.2%. By contrast, at a CRP level threshold of 60 mg/L, the rate of antibiotic misuse was 77.3%. A total of 39 of the 163 (23.9%) patients did not meet the guidelines for drug selection for viral CAP in adults. The unreasonable use of antibacterial drugs for the treatment of viral CAP in adults is a serious concern. Clinicians must reduce the unnecessary use of antibiotics.

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Fludarabine and intravenous busulfan conditioning with post-transplantation cyclophosphamide for allogeneic peripheral stem cell transplantation for adult patients with lymphoid malignancies: a prospective single-arm phase II study
Ling Wang, Lining Wang, Xing Fan, Wei Tang, Jiong Hu
Front. Med.    https://doi.org/10.1007/s11684-019-0730-8
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Post-transplantation cyclophosphamide (PT-Cy) alone or in combination with other immunosuppressive drugs has emerged as a promising strategy in the setting of allogeneic hematopoietic stem cell transplantation. Improved survival rate was reported in lymphoid malignancies following PT-Cy strategy compared with myeloid disease in non-myeloablative bone marrow transplant setting. Thus, we aimed to evaluate the safety and efficacy of PT-Cy combined with cyclosporine as graft-versus-host disease (GVHD) prophylaxis after myeloablative conditioning and T cell-replete peripheral stem cell transplantation in lymphoid malignancies. This single-arm phase II clinical trial (NCT01435447) involving 31 adult patients was conducted from January 2013 to June 2018. The donor-type neutrophil engraftment rate was 100%, and the overall incidence of grade II to IV and grade III to IV acute GVHD was 39% and 24%, respectively. The cumulative incidence rates of chronic GVHD (35%), including moderate to severe forms (10%), were reduced compared with those of the historical group (P=0.03 and P=0.04, respectively). With a median follow-up of 18 months, the estimated 2-year overall and event-free survival was 64.8% (95% confidence interval: 47.8%–86.7%) and 58.4% (95% CI: 41.9%–81.7%), respectively. The 2-year cumulative incidence rate of relapse was 19.5% (95% CI: 9.0%–35.8%), whereas the non-relapse mortality rate was 21.8% (95% CI: 11.3%–38.1%). These results demonstrated the feasibility of PT-Cy as GVHD prophylaxis in this clinical setting. This strategy could significantly reduce the incidence of chronic GVHD and its moderate to severe forms but not of acute GVHD and results in similar survival outcomes compared with the historical group. A prospective study with additional patients is warranted to confirm the role of PT-Cy in lymphoid malignancy.

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Prognostic value of fasting glucose on the risk of heart failure and left ventricular systolic dysfunction in non-diabetic patients with ST-segment elevation myocardial infarction
Hui Wang, Yang Zhang, Zhujun Shen, Ligang Fang, Zhenyu Liu, Shuyang Zhang
Front. Med.    https://doi.org/10.1007/s11684-020-0749-x
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Recent studies have shown that acute blood glucose elevation in patients with ST-segment elevation myocardial infarction (STEMI) suggests a poor prognosis. To investigate the effect of fasting blood glucose (FBG) on the risk of heart failure (HF) and left ventricular systolic dysfunction (LVSD) in non-diabetic patients undergoing primary percutaneous coronary intervention (PCI) for acute STEMI, we retrospectively recruited consecutive non-diabetic patients who underwent primary PCI for STEMI in our hospital from February 2003 to March 2015. The patients were divided into two groups according to the FBG level. A total of 623 patients were recruited with an age of 61.3±12.9 years, of whom 514 (82.5%) were male. The HF risk (odds ratio 3.401, 95% confidence interval (CI) 2.144–5.395, P <0.001) was significantly increased in patients with elevated FBG than those with normal FBG. Elevated FBG was also independently related to LVSD (β 1.513, 95%CI 1.282–1.785, P <0.001) in a multiple logistics regression analysis. In conclusion, elevated FBG was independently associated with 30-day HF and LVSD risk in non-diabetic patients undergoing primary PCI for STEMI.

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Factors influencing peak bone mass gain
Xiaowei Zhu, Houfeng Zheng
Front. Med.    https://doi.org/10.1007/s11684-020-0748-y
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Bone mass is a key determinant of osteoporosis and fragility fractures. Epidemiologic studies have shown that a 10% increase in peak bone mass (PBM) at the population level reduces the risk of fracture later in life by 50%. Low PBM is possibly due to the bone loss caused by various conditions or processes that occur during adolescence and young adulthood. Race, gender, and family history (genetics) are responsible for the majority of PBM, but other factors, such as physical activity, calcium and vitamin D intake, weight, smoking and alcohol consumption, socioeconomic status, age at menarche, and other secondary causes (diseases and medications), play important roles in PBM gain during childhood and adolescence. Hence, the optimization of lifestyle factors that affect PBM and bone strength is an important strategy to maximize PBM among adolescents and young people, and thus to reduce the low bone mass or osteoporosis risk in later life. This review aims to summarize the available evidence for the common but important factors that influence bone mass gain during growth and development and discuss the advances of developing high PBM.

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Linking key intervention timings to rapid declining effective reproduction number to quantify lessons against COVID-19
Zhihang Peng, Wenyu Song, Zhongxing Ding, Quanquan Guan, Xu Yang, Qiaoqiao Xu, Xu Wang, Yankai Xia
Front. Med.    https://doi.org/10.1007/s11684-020-0788-3
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Coronavirus disease 2019 (COVID-19) is currently under a global pandemic trend. The efficiency of containment measures and epidemic tendency of typical countries should be assessed. In this study, the efficiency of prevention and control measures in China, Italy, Iran, South Korea, and Japan was assessed, and the COVID-19 epidemic tendency among these countries was compared. Results showed that the effective reproduction number(Re) in Wuhan, China increased almost exponentially, reaching a maximum of 3.98 before a lockdown and rapidly decreased to below 1 due to containment and mitigation strategies of the Chinese government. The Re in Italy declined at a slower pace than that in China after the implementation of prevention and control measures. The Re in Iran showed a certain decline after the establishment of a national epidemic control command, and an evident stationary phase occurred because the best window period for the prevention and control of the epidemic was missed. The epidemic in Japan and South Korea reoccurred several times with the Re fluctuating greatly. The epidemic has hardly rebounded in China due to the implementation of prevention and control strategies and the effective enforcement of policies. Other countries suffering from the epidemic could learn from the Chinese experience in containing COVID-19.

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Altered white matter microarchitecture in Parkinson’s disease: a voxel-based meta-analysis of diffusion tensor imaging studies
Xueling Suo, Du Lei, Wenbin Li, Lei Li, Jing Dai, Song Wang, Nannan Li, Lan Cheng, Rong Peng, Graham J Kemp, Qiyong Gong
Front. Med.    https://doi.org/10.1007/s11684-019-0725-5
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This study aimed to define the most consistent white matter microarchitecture pattern in Parkinson’s disease (PD) reflected by fractional anisotropy (FA), addressing clinical profiles and methodology-related heterogeneity. Web-based publication databases were searched to conduct a meta-analysis of whole-brain diffusion tensor imaging studies comparing PD with healthy controls (HC) using the anisotropic effect size–signed differential mapping. A total of 808 patients with PD and 760 HC coming from 27 databases were finally included. Subgroup analyses were conducted considering heterogeneity with respect to medication status, disease stage, analysis methods, and the number of diffusion directions in acquisition. Compared with HC, patients with PD had decreased FA in the left middle cerebellar peduncle, corpus callosum (CC), left inferior fronto-occipital fasciculus, and right inferior longitudinal fasciculus. Most of the main results remained unchanged in subgroup meta-analyses of medicated patients, early stage patients, voxel-based analysis, and acquisition with <30 diffusion directions. The subgroup meta-analysis of medication-free patients showed FA decrease in the right olfactory cortex. The cerebellum and CC, associated with typical motor impairment, showed the most consistent FA decreases in PD. Medication status, analysis approaches, and the number of diffusion directions have an important impact on the findings, needing careful evaluation in future meta-analyses.

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