Diagnostic challenges from conflicting results of tests and imaging

Accurate diagnosis is the foundation of clinical care but accurate diagnosis is not easily reached in some cases.In rare instances,even a sophisticated multidisciplinary team at an academic medical center cannot reliably reach an accurate diagnosis after extensive testing and imaging,and has to wait until histological diagnosis or even autopsy results are available.The underlying reason of challenging diagnoses is mostly conflicting data from history,tests,and imaging that point to different diagnoses.In this issue of World Journal of Clinical Cases,Huffaker et al reported such a challenging case of a tricuspid mass in a patient with Li-Fraumeni syndrome.The case by Huffaker et al powerfully illustrates the occasional diagnostic challenges inherent in our current diagnostic approach and the current technology.Clinicians should realize that in rare situations,agnosticism in diagnosis is unavoidable but a treatment has to be initiated so long as the principle of primum non nocere is upheld.

Nationwide trends and predictors of inpatient mortality in 83884 transjugular intrahepatic portosystemic shunt

AIM: To evaluate and validate the national trends and predictors of in-patient mortality of transjugular intrahepatic portosystemic shunt (TIPS) in 15 years.METHODS: Using the National Inpatient Sample which is a part of Health Cost and Utilization Project, we identified a discharge-weighted national estimate of 83884 TIPS procedures performed in the United States from 1998 to 2012 using international classification of diseases-9 procedural code 39.1. The demographic, hospital and co-morbility data were analyzed using a multivariant analysis. Using multi-nominal logistic regression analysis, we determined predictive factors related to increases in-hospital mortality. Comorbidity measures are in accordance to the Comorbidity Software designed by the Agency for Healthcare Research and Quality.RESULTS: Overall, 12.3% of patients died during hospitalization with downward trend in-hospital mortality with the mean length of stay of 10.8 ± 13.1 d. Notable, African American patients (OR = 1.809 vs Caucasian patients, P < 0.001), transferred patients (OR = 1.347 vs non-transferred, P < 0.001), emergency admissions (OR = 3.032 vs elective cases, P < 0.001), patients in the Northeast region (OR = 1.449 vs West, P < 0.001) had significantly higher odds of in-hospital mortality. Number of diagnoses and number of procedures showed positive correlations with in-hospital death (OR = 1.249 per one increase in number of procedures). Patients diagnosed with acute respiratory failure (OR = 8.246), acute kidney failure (OR = 4.359), hepatic encephalopathy (OR = 2.217) and esophageal variceal bleeding (OR = 2.187) were at considerably higher odds of in-hospital death compared with ascites (OR = 0.136, P < 0.001). Comorbidity measures with the highest odds of in-hospital death were fluid and electrolyte disorders (OR = 2.823), coagulopathy (OR = 2.016), and lymphoma (OR = 1.842).CONCLUSION: The overall mortality of the TIPS procedure is steadily decreasing, though the length of stay has remained relatively constant. Specific patient ethnicity, location, transfer status, primary diagnosis and comorbidities correlate with increased odds of TIPS in-hospital death.

Newly discovered endocrine functions of the liver

The liver,the largest solid visceral organ of the body,has numerous endocrine functions,such as direct hormone and hepatokine production,hormone metabolism,synthesis of binding proteins,and processing and redistribution of metabolic fuels.In the last 10 years,many new endocrine functions of the liver have been discovered.Advances in the classical endocrine functions include delineation of mechanisms of liver production of endocrine hormones[including 25-hydroxyvitamin D,insulin-like growth factor 1(IGF-1),and angiotensinogen],hepatic metabolism of hormones(including thyroid hormones,glucagon-like peptide-1,and steroid hormones),and actions of specific binding proteins to glucocorticoids,sex steroids,and thyroid hormones.These studies have furthered insight into cirrhosis-associated endocrinopathies,such as hypogonadism,osteoporosis,IGF-1 deficiency,vitamin D deficiency,alterations in glucose and lipid homeostasis,and controversially relative adrenal insufficiency.Several novel endocrine functions of the liver have also been unraveled,elucidating the liver’s key negative feedback regulatory role in the pancreaticαcell-liver axis,which regulates pancreaticαcell mass,glucagon secretion,and circulating amino acid levels.Betatrophin and other hepatokines,such as fetuin-A and fibroblast growth factor 21,have also been discovered to play important endocrine roles in modulating insulin sensitivity,lipid metabolism,and body weight.It is expected that more endocrine functions of the liver will be revealed in the near future.

Hepatic artery stenosis angioplasty and implantation of Wingspan neurovascular stent: A case report and discussion of stenting in tortuous vessels

BACKGROUND Hepatic artery stenosis is a complication of orthotopic liver transplant occurring in 3.1%-7.4%of patients that can result in graft failure and need for retransplantation.Endovascular therapy with angioplasty and stenting has been used with a high degree of technical success and good clinical outcomes,but tortuous hepatic arteries present a unique challenge for intervention.Suitable stents for this application should be maneuverable and conformable while also exerting adequate radial force to maintain a patent lumen.CASE SUMMARY Herein we report our experience with a neurovascular Wingspan stent system in a challenging case of recurrent hepatic artery stenosis and discuss the literature of stenting in tortuous transplant hepatic arteries.CONCLUSION Wingspan neurovascular stent is self-expanding,has good conformability,and adequate radial resistance and as such it could be added to the armamentarium of interventionalists in the setting of a tortuous and stenotic transplant hepatic artery.

Antibody-fused interferons as an effective approach to enhance target specificity and antiviral efficacy of type I interferons

Interferons （IFNs） were first described for their ability to protect cells from viral infections [1]. Since these initial reports, three major types of IFNs have been described. Type I IFNs, including IFNβ and multiple IFNα subtypes, induce antiviral gene programs through the IFNα/β receptor, IFNAR; many of these genes are directly or indirectly involved in curbing viral replication and spread [2].

Atrial Septal Defect and Left Recurrent Laryngeal Nerve Paralysis: A Case of Ortner’s Syndrome and Literature Review

Introduction: Cardiovocal syndrome, or hoarseness resulting from vocal fold paralysis secondary to cardiovascular pathology, is commonly referred to as Ortner’s syndrome. We present a brief overview of vocal fold paralysis, present an illustrative case of Ortner’s syndrome, and provide a review of the pertinent literature. Here we aim to broaden one’s differential for vocal fold paralysis, discuss its importance as pertains to cardiovascular pathology and outcomes, and highlight the difficulties in therapeutic planning for these unique patients. Methods: A case report and literature review. Results: A 26-year-old female with an atrial septal defect and pulmonary hypertension presented with 5 months of hoarseness. Laryngoscopy revealed left vocal fold paralysis. Imaging from the skull base to chest showed an enlarged pulmonary artery (PA) in the absence of other abnormalities. Literature review suggests that this left laryngeal nerve paralysis results from nerve compression within the aortopulmonary window, a triangle defined by the aortic arch, PA, and ligamentumarteriosum. Imaging in our patient over 8 months demonstrated an increase in PA size from 3.9 to 4.2 cm correlating with the onset of hoarseness. Conclusions: Importantly, hoarseness second ary to laryngeal nerve compression in cardiovascular disease may correlate with a poorer prognosis, i.e., in thoracic aortic aneurysms and mitral valvestenosis. Awareness of vocal changes in the setting of cardiovascular disease improves diagnostic acumen in vocal foldparalysis.

Novel use of esophageal overtube and water flushes as a safety indicator and facilitator for the push technique in esophageal food impaction

Esophageal food impaction requires urgent endoscopic intervention either by extraction or pushing into the stomach.Due to risks of perforation,controversy exists between when to extract verses when to push the food bolus.There are no clear guidelines on when it is safe to push a food bolus;endoscopists rely on their subjective experiences and judgment.We present a case with a novel use of an esophageal overtube and water flushes to determine the safety of pushing a food bolus and facilitate passage into the stomach.

Mechanism of Mingjing Granules in Treating Wet Age-Related Macular Degeneration Based on Network Pharmacology and Experimental Verification

Objective:To analyze the potential mechanism of Mingjing granules in the treatment of wet age-related macular degeneration(wAMD)based on the research methods of network pharmacology and molecular docking approach and to provide a new reference for the currently limited treatment of wAMD.Materials and Methods:We searched TCMSP,GeneCards,OMIM,PharmGkb,TTD,and DrugBank database to screen the main active ingredients of Mingjing granules and their therapeutic targets of wAMD.The network of active components and targets was constructed using Cytoscape3.6.1 software,which was also used for the topological analysis of target genes.The network of Protein-Protein Interactions(PPI)was mapped using the String platform.We also used R language to do the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway for additional analysis.Molecular docking studies were finished by Chemoffice,Autodock,and Pymol.Finally,the efficacy of the Mingjing granules was examined in animal experiments,in which we used enzyme-linked immunosorbent assay to the contents of vascular endothelial growth factor(VEGF)and matrix metalloproteinase-9(MMP-9)levels in peripheral blood.Results:Active compounds,including quercetin,lignocaine,and kaempferol,were found.PPI network analysis showed that tumor necrosis factor(TNF),MMP-9,epidermal growth factor(EGF),prostaglandin-endoperoxide synthase 2(PTGS2),and caspase-3(CASP3)were related to both Mingjing granules and wAMD.GO and KEGG pathway analysis showed that these targets were mainly involving lipids and atherosclerosis,TNF,and interleukin-17(IL-17)signaling pathways.Docking studies suggested that quercetin and luteolin can fit in the binding pocket of four target proteins(CASP3,EGF,PTGS2,and TNF).In the vivo experiment,the Mingjing granules were found to be effective on the expression of VEGF and MMP-9 in peripheral blood.Conclusions:This study initially reveals the multi-constituent,multi-target,and multi-pathway mechanism of action of Mingjing granules in the treatment of wAMD and implies the inhibition of choroidal neovascularization may be related to the expression of VEGF and MMP-9.

微管相关蛋白2在胰腺神经内分泌肿瘤组织中的表达及预后意义

目的:探索微管相关蛋白2(microtubule-associated protein 2,MAP2)与微管相关蛋白1B(microtubule-associated protein 1B,MAP1B)在预测胰腺神经内分泌肿瘤(pancreatic neuroendocrine tumors,PNETs)患者预后中的意义。方法:收集1999年12月至2016年12月来自于北京协和医院、中山大学附属第一医院、复旦大学上海癌症中心和Cedars-Sinai医学中心(洛杉矶)193例患者的193个原发肿瘤标本。免疫组织化学染色法分别检测193例、120例PNETs组织中MAP2、MAP1B的表达,随后分析蛋白表达与患者临床病理特征及预后的关系。结果:MAP2和MAP1B在PNETs患者中的阳性率分别为45.6%(88/193)和64.2%(77/120)。MAP2表达阳性的患者的总生存好于阴性患者(P=0.012)。另外,MAP2阳性Ⅱ、Ⅲ期患者的总生存也优于阴性者(P=0.017)。然而,MAP1B的表达与肿瘤大小、转移、肿瘤组织学分级、临床分期、总生存、无病生存均无相关性(P>0.05)。结论:MAP2为潜在的预测PNETs患者预后的指标。

Introducing Considerations in the Translation of Chinese Medicine

This article introduces the document, Considerations in the Translation of Chinese Medicine, published in PDF form online in both Chinese and English. This 20-page document includes several sections describing why the Considerations is necessary, the specificity of texts in Chinese medicine; the history of translation in Chinese medicine; who constitutes an ideal translator of Chinese medicine; what types of language exist in Chinese medicine; and specific issues in the translation of Chinese medicine, such as domestication versus foreignization, technical terminology, period-specific language, style, polysemy, and etymological translation. The final section offers a brief advisory for consumers, and concludes with a call to further discussion, and action, specifically in the development of international collaborative efforts towards the creation of more rigorous guidelines for the translation of Chinese medicine. The current article provides an overview of several of these sections, and includes links to the original document.

Infectious keratitis in Vietnam:etiology,organisms,and management at Vietnam National Eye Hospital

AIM:To report the etiologies,risk factors,treatments,and outcomes of infectious keratitis(IK)at a major Vietnamese eye hospital.METHODS:This is a retrospective review of all cases of IK at Vietnam National Eye Hospital(VNEH)in Hanoi,Vietnam.Medical histories,demographics,clinical features,microbiological results,and treatment outcomes were reviewed.RESULTS:IK was diagnosed in 1974 eyes of 1952 patients,with ocular trauma being the greatest risk factor for IK(34.2%),frequently resulting from an agriculturerelated injur y(53.3%).The mean duration between symptom onset and presentation to VNEH was 19.3±14.4 d,and 98.7%of patients had been treated with topical antibiotic and/or antifungal agents prior to evaluation at VNEH.Based on smear results of 1706 samples,the most common organisms identified were bacteria(n=1107,64.9%)and fungi(n=1092,64.0%),with identification of both bacteria and fungi in 614(36.0%)eyes.Fifty-five of 374 bacterial cultures(14.7%)and 426 of 838 fungal cultures(50.8%)were positive,with the most commonly cultured pathogens being Pseudomonas aeruginosa,Streptococcus pneumonia,Fusarium spp.,and Aspergillus spp.Corneal perforation and descemetocele developed in 391(19.8%)and 93(4.7%)eyes,respectively.Medical treatment was successful in resolving IK in 50.4%eyes,while 337(17.1%)eyes underwent penetrating or anterior lamellar keratoplasty.Evisceration was performed in 7.1%of eyes,most commonly in the setting of fungal keratitis.CONCLUSION:Ocular trauma is a major risk factor for IK in Vietnam,which is diagnosed in almost 400 patients each year at VNEH.Given this,and as approximately one quarter of the eyes that develop IK require corneal transplantation or evisceration,greater emphasis should be placed on the development of prevention and treatment programs for IK in Vietnam.

Clinical characteristics and outcomes associated with nasal intermittent mandatory ventilation in acute pediatric respiratory failure

AIM To characterize the clinical course and outcomes of nasal intermittent mandatory ventilation(NIMV) use in acute pediatric respiratory failure.METHODS We identified all patients treated with NIMV in the pediatric intensive care unit(PICU) or inpatient general pediatrics between January 2013 and December 2015 at two academic centers.Patients who utilized NIMV with other modes of noninvasive ventilation during the same admission were included.Data included demographics,vital signs on admission and prior to initiation of NIMV,pediatric risk of mortality Ⅲ(PRIsM-Ⅲ) scores,complications,respiratory support characteristics,PICU and hospital length of stays,duration of respiratory support,and complications.Patients who did not require escalation to mechanical ventilation were defined as NIMV responders;those who required escalation to mechanical ventilation(MV) were defined as NIMV nonresponders.NIMV responders were compared to NIMV non-responders.RESULTS Forty-two patients met study criteria.six(14%) failed treatment and required MV.The majority of the patients(74%) had a primary diagnosis of bronchiolitis.The median age of these 42 patients was 4 mo(range 0.5-28.1 mo,IQR 7,P = 0.69).No significant difference was measured in other baseline demographics and vitals on initiation of NIMV;these included age,temperature,respiratory rate,O2 saturation,heart rate,systolic blood pressure,diastolic blood pressure,and PRIsM-Ⅲ scores.The duration of NIMV was shorter in the NIMV nonresponder vs NIMV responder group(6.5 h vs 65 h,P < 0.0005).Otherwise,NIMV failure was not associated with significant differences in PICU length of stay(LOs),hospital LOs,or total duration of respiratory support.No patients had aspiration pneumonia,pneumothorax,or skin breakdown.CONCLUSION Most of our patients responded to NIMV.NIMV failure is not associated with differences in hospital LOs,PICU LOs,or duration of respiratory support.

Combating an invisible enemy: The American military response to global pandemics

The present moment is not the first time that America has found itself at war with a pathogen during a time of international conflict. Between crowded barracks at home and trenches abroad, wartime conditions helped enable the spread of influenza in the fall of 1918 during World War I such that an estimated 20%–40% of U.S. military members were infected. While the coronavirus disease 2019(COVID-19) pandemic is unparalleled for most of today's population, it is essential to not view it as unprecedented lest the lessons of past pandemics and their effect on the American military be forgotten. This article provides a historical perspective on the effect of the most notable antecedent pandemic, the Spanish Influenza epidemic, on American forces with the goal of understanding the interrelationship of global pandemics and the military, highlighting the unique challenges of the current pandemic, and examining how the American military has fought back against pandemics both at home and abroad, both 100 years ago and today.

Case Report: Autoimmune Disease Triggered by Exposure to Hair Straightening Treatment Containing Formaldehyde

Formaldehyde (FHO) is a multipurpose chemical that is an eye, nose, throat and skin irritant, sensitizer and allergen, as well as a class 1 human carcinogen. Brazilian hair treatments, containing high levels of FHO (up to 11%), have become regularly used that have the potential to expose clients to toxic levels in excess of current regulatory standards. We report on a patient who underwent a single hair treatment and subsequently developed an autoimmune disease. We review the relevant literature on autoimmune disease and formaldehyde exposure. Our case adds to existing knowledge and suggests that physicians ask their patients about commercial products that contain formaldehyde when diagnosing autoimmune conditions.

Signaling pathways in osteogenesis and osteoclastogenesis:Lessons from cranial sutures and applications to regenerative medicine

One of the simplest models for examining the interplay between bone formation and resorption is the junction between the cranial bones.Although only roughly a quarter of patients diagnosed with craniosynostosis have been linked to known genetic disturbances,the molecular mechanisms elucidated from these studies have provided basic knowledge of bone homeostasis.This work has translated to methods and advances in bone tissue engineering.In this review,we examine the current knowledge of cranial suture biology derived from human craniosynostosis syndromes and discuss its application to regenerative medicine.

Storylines of family medicine Ⅱ:foundational building blocks—context,community and health

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine,as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world.In‘Ⅱ:foundational building blocks—context,community and health’,authors address the following themes:‘Context—grounding family medicine in time,place and being’,‘Recentring community’,‘Community-oriented primary care’,‘Embeddedness in practice’,‘The meaning of health’,‘Disease,illness and sickness—core concepts’,‘The biopsychosocial model’,‘The biopsychosocial approach’and‘Family medicine as social medicine.’May readers grasp new implications for medical education and practice in these essays.

Using the rPatlak plot and dynamic FDG-PET to generate parametric images of relative local cerebral metabolic rate of glucose

Local cerebral metabolic rate of glucose(LCMRGlc) is an important index for the description of neural function.Dynamic 18 F-fluoro-2-deoxy-D-glucose(FDG) positron emission tomography(PET) has been used for quantitative imaging of LCMRGlc in humans,but is seldom used routinely because of the difficulty in obtaining the input function noninvasively.A reference tissue-based Patlak plot model(rPatlak) was proposed to generate parametric images of LCMRGlc in a quantitative dynamic FDG-PET study without requiring blood sampling.Dynamic emission scans(4×0.5,4×2 and 10×5 min) were acquired simultaneously with an IV bolus injection of 155 MBq of FDG.Arterial blood samples were collected during the scans via a catheter placed in the radial artery.Simulation data were also generated using the same scan sequence.The last ten scan data sets were used in a graphical analysis using the Patlak plot.The ratio of LCMRGlc estimated from the original Patlak(oPatlak,using plasma input) was used as the gold standard,and the standardized uptake value ratio(SUVR) was also calculated for comparison.Eight different tissues including white matter,gray matter,and whole brain were chosen as reference tissues for evaluation.Regardless of the reference region used,the slopes in the linear regression between oPatlak and rPatlak were closer to unity than the regression slopes between oPatlak and SUVR.The intercepts for the former were also closer to 0 than those for the latter case.The squared correlation coefficients were close to 1.0 for both cases.This showed that the results of rPatlak were in good agreement with those of oPatlak,however,SUVR exhibited more deviation.The simulation study also showed that the relative variance and bias for rPatlak were less than those for SUVR.The images obtained with rPatlak were very similar to those obtained with oPatlak,while there were differences in the relative spatial distribution between the images of SUVR and oPatlak.This study validates that the rPatlak method is better than the SUVR method and is a good approximation to the oPatlak method.The new method is suitable for generating LCMRGlc parametric images noninvasively.

用rPatlak图解及动态FDG-PET方法生成脑局部葡萄糖代谢率参数图

脑局部葡萄糖代谢率(LCMRGlc)是反映脑功能状态的重要指标,18F标记的2-脱氧葡萄糖作示踪剂的动态正电子发射断层扫描(FDG-PET)方法已被用于人脑LCMRGlc定量参数成像,但由于原有的方法需要输入函数,这对人体是有损伤的,因而很少用于临床.本文采用基于参考区的Patlak图形近似模型(rPatlak)和动态FDG-PET成像方法生成LCMRGlc定量参数图,这种方法无需输入函数因而无需采集动脉血样.在对被试进行弹丸静脉注射155MBq的FDG后同步启动脑部动态PET扫描,扫描序列为4×0.5,4×2和10×5min,且扫描期间通过事先植入动脉的导管采集血样,以获得本研究中作为对比的金标准—原始Patlak图形近似方法(oPatlak)所需的输入函数.研究中的模拟数据也采用了同样的扫描序列.两种Patlak图形近似方法采用了最后的10个PET扫描数据.用需要血样数据的oPatlak方法获得相对于参考区的LCMRGlc比值作为金标准,标准摄取值比值(SUVR)也被计算并作为比对.对于实际数据,选择包括白质、灰质、全脑等8个不同脑区作参考区来进行评估.实验结果表明,无论选择哪个脑区作参考区,rPatlak与oPatlak的结果很相似,但SUVR的结果就差得多.模拟研究结果还表明,rPatlak结果的偏差及误差都小于SUVR.最后,用rPatlak方法生成的LCMRGlc定量参数图与oPatlak生成的很相似,但SUVR与oPatlak间就有较大差异.本研究表明,rPatlak方法好于SUVR方法,可以作为oPatlak方法的很好近似,新方法适合用来无损伤地生成LCMRGlc定量参数图.