简介：AbstractBackgroud:Aspirin-exacerbated respiratory disease (AERD) is a difficult-to-treat syndrome where timely diagnosis and initiation of disease-specific therapies are pertinent to improved patient outcomes.Objective:To characterize the most common timeline for development of the clinical triad [asthma, nasal polyposis, and reactions to nonsteroidal anti-inflammatory drugs (NSAIDs)], identify barriers to prompt diagnosis of AERD, and describe indications for an aspirin challenge to facilitate accurate diagnosis.Methods:Six hundred ninety-seven patients with diagnosed AERD and history of at least one sinus surgery to remove nasal polyps were identified in the Brigham and Women’s Hospital AERD registry. Patient reported age at disease onset of asthma, nasal polyposis, and age of first NSAID reaction were obtained from 2013 to 2019 at enrollment.Results:Of the 697 patients identified, diagnosis of asthma preceded diagnosis of nasal polyposis and first NSAID reaction, although there was considerable variability between patients.Conclusions:Prompt diagnosis of AERD is important for patient and provider education and improved care of this difficult-to-treat population of patients. Consider diagnostic aspirin challenge in patients without historical reactions to NSAIDs who have an otherwise compatible clinical history, specifically in patients who take daily low-dose aspirin, leukotriene modifiers, avoid NSAIDs, or who are severely symptomatic at baseline where it would be difficult to identify an acute worsening of symptoms.

简介：AbstractBackground:Sleep disorders are common but under-researched symptoms in patients with multiple system atrophy (MSA). We investigated the frequency and factors associated with sleep-related symptoms in patients with MSA and the impact of sleep disturbances on disease severity.Methods:This cross-sectional study involved 165 patients with MSA. Three sleep-related symptoms, namely Parkinson’s disease (PD)-related sleep problems (PD-SP), excessive daytime sleepiness (EDS), and rapid eye movement sleep behavior disorder (RBD), were evaluated using the PD Sleep Scale-2 (PDSS-2), Epworth Sleepiness Scale (ESS), and RBD Screening Questionnaire (RBDSQ), respectively. Disease severity was evaluated using the Unified MSA Rating Scale (UMSARS).Results:The frequency of PD-SP (PDSS-2 score of ≥18), EDS (ESS score of ≥10), and RBD (RBDSQ score of ≥5) in patients with MSA was 18.8%, 27.3%, and 49.7%, respectively. The frequency of coexistence of all three sleep-related symptoms was 7.3%. Compared with the cerebellar subtype of MSA (MSA-C), the parkinsonism subtype of MSA (MSA-P) was associated with a higher frequency of PD-SP and EDS, but not of RBD. Binary logistic regression revealed that the MSA-P subtype, a higher total UMSARS score, and anxiety were associated with PD-SP; that male sex, a higher total UMSARS score, the MSA-P subtype, and fatigue were associated with EDS; and that male sex, a higher total UMSARS score, and autonomic onset were associated with RBD in patients with MSA. Stepwise linear regression showed that the number of sleep-related symptoms (PD-SP, EDS, and RBD), disease duration, depression, fatigue, and total Montreal Cognitive Assessment score were predictors of disease severity in patients with MSA.Conclusions:Sleep-related disorders were associated with both MSA subtypes and the severity of disease in patients with MSA, indicating that sleep disorders may reflect the distribution and degree of dopaminergic/non-dopaminergic neuron degeneration in MSA.

简介：AbstractAspirin-exacerbated respiratory disease (AERD) is characterized by the triad of chronic rhinosinusitis with nasal polyposis, adult-onset asthma and non-IgE mediated reactions to aspirin and other cyclooxygenase-1 (COX-1) inhibitors. Patients with AERD are dependent on COX-1 activity to maintain production of prostaglandin (PG) species, such as PGE2, which maintain physiologic levels of inflammation and limit the production of pro-inflammatory cysteinyl leukotrienes. The endogenous cannabinoid system is a family of immunomodulatory lipids and their innate g-protein coupled receptors that are closely related to arachidonic acid and may modulate inflammation via several pathways, including the direct production of metabolically active prostaglandin glycerol-esters. A recent pilot study has identified the significant up-regulation of the peripherally expressed, type-2 cannabinoid receptor (CB2) in AERD nasal polyps versus control tissues from patients with either allergic fungal rhinosinusitis or no history of chronic sinonasal inflammation. These early findings suggest the involvement of increased endogenous cannabinoid activity in prostaglandin deficient states such as AERD. Future study is needed to explore the significance of these findings, with specific investigation of the impact of CB2 activation on markers of airway inflammation, as well as the potential to measure CB2 expression as a screening biomarker for the evaluation of unrecognized disease.

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简介：瞄准：在为Peyronie的疾病在外科的过程以后改进耐心的满足的适当外科的过程的病历，外科手术前的评估，真实期望，和选择上讨论重要的点。方法：在Peyronie的疾病的途径的最近的进展基于文学和个人经验被讨论。有关外科的指示，耐心的选择，外科的技术，和移植的问题被讨论。借助于grafting提议的阴茎弯曲的凸的方面上的变长的过程从重建立场的最好的可能的获得。阴茎校正和刚硬被要求完成一根完全功能的阴茎。大多数病人经历联系可勃起的机能障碍(编辑)，并且独自的阴茎弄直不能是足够的恢复完全的功能。25个病人被提交与阴茎修复术植入的伴随物在长度和尺寸上总计阴茎重建。最大的长度恢复由把的神经与血管的捆的长度可能、有限。吝啬的年龄是55.4年(32-69年)和弯曲74.2±的吝啬的角度22.4°(0-100°)。心囊的移植被用来盖住缺点。吝啬的后续时间是11.2±5.9个月(3-22月)。结果：吝啬的功能的阴茎长度获得是3.40±0.73厘米(2-5厘米)。阴茎修复术笔直地维持了阴茎。没有感染发生了。性交在所有病人和所有报导恢复自尊被恢复。结论：对外科疗法的改善耐心的满足为恢复功能的阴茎(长度和刚硬)象外科的技术的广泛的讨论一样在稳定的疾病，阴茎弄短的、脉管、可勃起的地位，耐心的决定和选择上包括合适的外科手术前的评估。长度和尺寸恢复为自尊和耐心的满足是很重要的。

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简介：AbstractParkinson disease (PD) is the second-most common neurodegenerative disorder. Its main pathological mechanism is the selective degeneration and deletion of dopaminergic neurons in the dense part of the substantia nigra and the damage of dopaminergic neurons caused by the abnormal deposition of a Lewy body, leading to a decreased dopamine level. Positron emission computed tomography (PET)/single photon emission computed tomography (SPECT) is a molecular imaging technology that can directly or indirectly reflect changes in molecular levels by using a specific tracer. With the research and development on the tracers of related enzymes for labeling dopamine transporter and dopamine receptor and for being involved in dopamine formation, this imaging technology has been applied to all aspects of PD research. It not only contributes to clinical work but also provides an important theoretical basis for exploring the pathological mechanism of PD at a molecular level. Therefore, this review discusses the application value of PET/SPECT in PD in terms of early diagnosis, disease severity evaluation, clinical manifestations, differential diagnosis, and pathological mechanism.

简介：AbstractImportance:Graves’ disease (GD) is rare in children under the age of 7 years. Children with this disease exhibit greater thyrotoxicity at diagnosis and require a longer course of medical therapy, compared with pubertal and postpubertal children and adults.Objective:To investigate the clinical features and identify predictors of remission in children under the age of 7 years with GD.Methods:This retrospective study included 77 children who were diagnosed with GD under the age of 7 years and were treated in the Department of Endocrinology, Beijing Children’s Hospital from 2010 to 2018. Clinical manifestations, laboratory data, and follow-up records were collected for all patients. Children who achieved remission of treatment with methimazole were compared with those who had persistent disease to identify which variables were associated with remission; multiple logistic regression and Cox regression analyses were used to evaluate interactions among predictive variables.Results:Sixty-three boys and 14 girls were included; the median age at diagnosis was 4.2 years (interquartile range: 3.2-5.3 years). Forty-six (56.7%) patients had no family history of thyroid disease, 17 patients had family history of thyroid disease and 14 patients with unknown family history. Of the 77 patients, 18 (23.4%) patients achieved remission of treatment with methimazole and 59 patients did not; moreover, 51 (66.2%) had Graves’ ophthalmopathy. Univariate analyses revealed no significant differences between the remission group and non-remission group in terms of age at diagnosis, sex, initial goiter size, or initial thyroid hormone concentration. However, there were a trend of correlation between the initial level of thyroid peroxidase antibody (TPOAb) and remission status (univariate analysis OR 1.002, P = 0.038; multivariate analysis OR 1.004, P = 0.019). Similar results were observed in univariate analysis of the initial thyrotropin receptor antibody (TRAb) level, but this association was not significant in multivariate analysis. Cox regression analyses revealed that children with high TRAb level required longer duration of remission, compared with low TRAb level (OR 0.950, 95% CI 0.904-0.997, P = 0.037).Interpretation:Initial TRAb level was an independent predictor of remission outcome in young children under the age of 7 years with GD. Initial TRAb level may predict the likelihood of remission in patients with young-age-of-onset GD.

简介：ObjectivesToassesswhetherstatinsreduceall-causemortalityandCVeventsinelderlypeoplewithoutestablishedCVdisease.BackgroundSinceageingofthepopulationissteadilyraising,preventionofcardiovascular(CV)diseaseintheelderlyisrelevant.InelderlypatientswithpreviousCVevents,useofstatinsisrecommendedbyguidelines,whereasbenefitsofthesedrugsinelderlysubjectswithoutpreviousCVeventsarestilldebated.MethodsRandomizedtrialscomparingstatinsversusplaceboandreportingall-causeandCVmortality,myocardialinfarction(MI),stroke,andnewcanceronsetinelderly(>65yearsold)subjectswithoutestablishedCVdiseasewereincluded.ResultsEighttrialsenrolling24,674subjects(42.7%females;meanage73.0+2.9;meanfollow-up3.5+1.5years)wereincludedinanalyses.Statins,comparedtoplacebo,significantlyreducedtheriskofMIby39.4%(relativerisk[RR]:0.606[95%confidenceinterval(CI):0.434to0.847];P=0.003),aswellastheriskofstrokeby23.8%(RR:0.762[CI:0.626to0.926];P=0.006).Incontrast,theriskofall-causedeath(RR:0.941[CI:0.856to1.035];P=0.210)andofCVdeath(RR:0.907[CI:0.686to1.199];P=0.493)werenotsignificantlyreduced.Newcanceronsetdidnotdifferbetweenstatin-comparedtoplacebotreatedsubjects(RR:0.989[CI:0.851to1.151];P=0.890).ConclusionsPInelderlysubjectsathighCVriskwithoutestablishedCVdisease,statinssignificantlyreducetheincidenceofMIandstroke,butdonotsignificantlyprolongsurvivalintheshort-term.

简介：ObjectivesTodetectionofchlamydiapneumoniae(Cpn)DNAinthecirculatingmononuclearcellfractionsofcoronaryheartdiseaseandtoinvestigatetheassociationbetweeninfectionwithchlamydiapneumoniaeandcoronaryheartdisease(CHD)andprospectivelywhetherblood-basednestedpolymerasechainreaction(nPCR)isusefulinidentifyingCpninfection.MethodsTheperipheralbloodmononuclearcell(PBMC)CpnDNAwasexaminedusingnPCRtechniqueandconfirmedbyelectrophoresisin150patientswithCHD.Select55patientswithclinicalsuspectedCHDbutangiographyresultarenormalascontrolgroup(CG).Thenweconductedaprospective,randomized,double-blind,placebo-controlledstudyof6monthsofazithromycinandplacebotreatmentinCHDgroup.PatientswithCpnDNApositivewerethenrandomizedtoreceiveazithromycinorplacebo.Aftertreatmentbloodsamplewerecollectedforrepeatedmeasurement.ResultsChlamydiapneumoniaeDNAwasdetectedin49(32.7%)of150personswithCHDandin1(1.8%)of55personswithcontrolgroup,oddsratio26.2,95%confidenceinterva13.52-194.98.ThepositivityratesofnPCRinCHDgroupswerehigherthanthoseincontrolgroup.16cases(29.1%)inlatentcoronaryheartdiseases(LCHD)group,19cases(39.6%)inunstableangina(UAP)group,and14cases(29.9%)inacutemyocardialinfarction(AMI)groupwereCpnpositivebynPCR.TherewerenosignificantdifferenceamonginAMIUAPandLCHDgroup.ThereweresignificiantdifferenceinCpnDNAnegativeratesaftertheazithromycinandtheplacebotreatment.ConclusionsChlamydiapneumoniaeispresentinPBMCofasignificantproportionofpersonswithCHD.Thepotentialroleofchlamydiapneumoniaeincoronaryatherosclerosismaythereforebemorerelatedtoaccelerationofdiseaseorsystemiceffectsbypersistentinfectionthantosuddeninitiationofprogressivecoronaryarterydiseasebyacuteinfection.ThedetectionofCpnDNAinPBMCwithnPCRmaybeofgreatvalueforidentifyingCpncarriersandfo

简介：hepatocellular癌(HCC)的发展被归因于几个因素，包括长期的病毒的感染，白酒消费，到黄麴毒素B1的暴露和新陈代谢的混乱。几份最近的报告证明了HCC能当另外的内在的高风险的肝疾病不在时与长期的Crohns疾病(CD)发生在病人。然而，可以在CD和hepatocarcinogenesis之间有一个协会为这的精确机制要求进一步的调查。

简介：AIM:Toevaluatetherelationshipbetweenthiopu-rineS-methyltransferase(TPMT)polymorphismsandthiopurine-inducedadversedrugreactions(ADRs)ininflammatoryboweldisease(IBD).METHODS:EligiblearticlesthatcomparedthefrequencyofTPMTpolymorphismsamongthiopurine-tolerantand-intolerantadultIBDpatientswereincluded.StatisticalanalysiswasperformedwithReviewManager5.0.Sub-analysis/sensitivityanalysiswasalsoperformed.RESULTS:Ninestudiesthatinvestigatedatotalof1309participantsmetourinclusioncriteria.Theinci-denceofTPMTgenemutationwasincreased2.93-fold(95%CI:1.68-5.09,P=0.0001)and5.93-fold(95%CI:2.96-11.88,P<0.00001),respectively,inIBDpatientswiththiopurine-inducedoverallADRsandbonemarrowtoxicity(BMT),comparedwithcontrols.TheORforTPMTgenemutationinIBDpatientswiththiopurine-inducedhepatotoxicityandpancreatitiswas1.51(95%CI:0.54-4.19,P=0.43)and1.02(95%CI:0.26-3.99,P=0.98)vscontrols,respectively.CONCLUSION:Thismeta-analysissuggeststhattheTPMTpolymorphismsareassociatedwiththiopurine-inducedoverallADRsandBMT,butnotwithhepatotoxicityandpancreatitis.

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简介：AbstractBackground:The antioxidant effects of bilirubin in Parkinson’s disease (PD) have recently gained much attention from the research community. However, results from these studies have been conflicting. This meta-analysis is conducted to assess the relationship between the serum bilirubin concentration and the risk of PD.Methods:Two reviewers performed a systematic literature search across five databases (MEDLINE, PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials). The case-control studies regarding bilirubin levels in PD patients published up to April 2020 were included. These studies were subjected to rigorous scrutiny and data extraction to determine the standard mean difference (SMD) and the 95% confidence interval (CI), which were analyzed using the Stata V.12.0 statistical software.Results:A total of eight studies which included 1463 PD cases and 1490 controls were incorporated into our meta-analysis. SMD analysis showed that there was a higher total bilirubin (TBIL) and direct bilirubin (DBIL) levels in PD patients compared with controls (for TBIL, SMD: 0.300, 95% CI: 0.050-0.549, P = 0.018; for DBIL, SMD: 0.395, 95% CI: 0.102-0.688, P = 0.008). However, no significant relationship was found between the serum indirect bilirubin and PD patients (SMD: -0.223, 95% CI: -0.952-0.505, P = 0.548). A subgroup analysis based on ethnicity indicated that the serum TBIL was higher in PD patients of Caucasian descent in contrast to matched healthy controls (SMD: 0.511, 95% CI: 0.324-0.698, P = 0.000, I2 = 58.0%).Conclusion:Higher serum bilirubin levels in PD patients suggest that bilirubin might play a role in the pathogenesis of PD and have the potential to be utilized as a biochemical marker for PD diagnosis and treatment.

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简介：AbstractThe common cerebral small vessel disease (CSVD) neuroimaging features visible on conventional structural magnetic resonance imaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. The CSVD neuroimaging features have shared and distinct clinical consequences, and the automatic quantification methods for these features are increasingly used in research and clinical settings. This review article explores the recent progress in CSVD neuroimaging feature quantification and provides an overview of the clinical consequences of these CSVD features as well as the possibilities of using these features as endpoints in clinical trials. The added value of CSVD neuroimaging quantification is also discussed for researches focused on the mechanism of CSVD and the prognosis in subjects with CSVD.

简介：AbstractBackground:Neglected tropical diseases (NTDs) have long been overlooked in the global health agenda. They are intimately related to poverty, cause important local burdens of disease, but individually do not represent global priorities. Yet, NTDs were estimated to affect close to 2 billion people at the turn of the millennium, with a collective burden equivalent to HIV/AIDS, tuberculosis, or malaria. A global response was therefore warranted.Main text:The World Health Organization (WHO) conceived an innovative strategy in the early 2000s to combat NTDs as a group of diseases, based on a combination of five public health interventions. Access to essential NTD medicines has hugely improved thanks to strong public-private partnership involving the pharmaceutical sector. The combination of a WHO NTD roadmap with clear targets to be achieved by 2020 and game-changing partner commitments endorsed in the London Declaration on Neglected Tropical Diseases, have led to unprecedented progress in the implementation of large-scale preventive treatment, case management and care of NTDs. The coming decade will see as challenges the mainstreaming of these NTD interventions into Universal Health Coverage and the coordination with other sectors to get to the roots of poverty and scale up transmission-breaking interventions. Chinese expertise with the elimination of multiple NTDs, together with poverty reduction and intersectoral action piloted by municipalities and local governments, can serve as a model for the latter. The international community will also need to keep a specific focus on NTDs in order to further steer this global response, manage the scaling up and sustainment of NTD interventions globally, and develop novel products and implementation strategies for NTDs that are still lagging behind.Conclusions:The year 2020 will be crucial for the future of the global response to NTDs. Progress against the 2020 roadmap targets will be assessed, a new 2021-2030 NTD roadmap will be launched, and the London Declaration commitments will need to be renewed. It is hoped that during the coming decade the global response will be able to further build on today's successes, align with the new global health and development frameworks, but also keep focused attention on NTDs and mobilize enough resources to see the effort effectively through to 2030.