健康人年龄相关基底节铁沉积的定量分析

目的以T1WMRI测量得出的R2＊和原始信号强度，采用以体素为基础的弛豫时间测量（VBR）以确定不同年龄正常志愿者基底节铁沉积量，并与文献报道的尸检组织铁浓度进行比较。材料与方法本研究经伦理委员会批准，获取了受试者或受试者父母的书面知情同意书。80例受试者（女41例．男39例：年龄1～80岁）接受了1．5TMR检查。

合并于肝细胞癌的门静脉血栓形成增强超声与螺旋CT的检出及定性

本研究的目的是对比增强超声（CEUS）与螺旋CT对肝细胞癌（HCC）并发门静脉血栓形成的检出与定性。50例US和多普勒US发现门静脉内血栓形成并经穿刺活检证实的HCC病人被纳入研究。其中13个血栓累及门静脉主干，37个血栓累及门静脉肝段分支。血栓活检后1周内行CEUS和CT检查。由有经验的放射医生以盲法根据每种影像技术分别做出血栓（有／无）与血栓性质（恶性／良性）的诊断，并同病理结果对照，确定血栓检出与定性的准确性。

Predicting mortality in patients with acute heart failure:Role of risk scores

Acute heart failure is a leading cause of hospitalization and death,and it is an increasing burden on health care systems. The correct risk stratification of patients could improve clinical outcome and resources allocation,avoiding the overtreatment of low-risk subjects or the early,inappropriate discharge of high-risk patients. Many clinical scores have been derived and validated for in-hospital and post-discharge survival; predictive models include demographic,clinical,hemodynamic and laboratory variables. Data sets are derived from public registries,clinical trials,and retrospective data. Most models show a good capacity to discriminate patients who reach major clinical end-points,with C-indices generally higher than 0.70,but their applicability in realworld populations has been seldom evaluated. No study has evaluated if the use of risk score-based stratification might improve patient outcome. Some variables(age,blood pressure,sodium concentration,renal function) recur in most scores and should always be considered when evaluating the risk of an individual patient hospitalized for acute heart failure. Future studies will evaluate the emerging role of plasma biomarkers.

Ventricular repolarization measures for arrhythmic risk stratification

Ventricular repolarization is a complex electrical phenomenon which represents a crucial stage in electrical cardiac activity. It is expressed on the surface electrocardiogram by the interval between the start of the QRS complex and the end of the T wave or U wave(QT). Several physiological, pathological and iatrogenic factors can influence ventricular repolarization. It has been demonstrated that small perturbations in this process can be a potential trigger of malignant arrhythmias, therefore the analysis of ventricular repolarization represents an interesting tool to implement risk stratification of arrhythmic events in different clinical settings. The aim of this review is to critically revise the traditional methods of static analysis of ventricular repolarization as well as those for dynamic evaluation, their prognostic significance and the possible application in daily clinical practice.

Plaque imaging with CT coronary angiography:Effect of intra-vascular attenuation on plaque type classification

AIM: To assess the attenuation of non-calcified atherosclerotic coronary artery plaques with computed tomography coronary angiography (CTCA). METHODS: Four hundred consecutive patients underwent CTCA (Group 1: 200 patients, Sensation 64 Cardiac, Siemens; Group 2: 200 patients, VCT GE Healthcare, with either Iomeprol 400 or Iodixanol 320, respectively) for suspected coronary artery disease (CAD). CTCA was performed using standard protocols. Image quality (score 0-3), plaque (within the accessible non-calcified component of each non-calcified/mixed plaque) and coronary lumen attenuation were measured. Data were compared on a per-segment/per-plaque basis. Plaques were classified as fibrous vs lipid rich based on different attenuation thresholds. A P < 0.05 was considered significant. RESULTS: In 468 atherosclerotic plaques in Group 1 and 644 in Group 2, average image quality was 2.96 ± 0.19 in Group 1 and 2.93 ± 0.25 in Group 2 (P ≥ 0.05). Coronary lumen attenuation was 367 ± 85 Hounsfield units (HU) in Group 1 and 327 ± 73 HU in Group 2 (P < 0.05); non-calcified plaque attenuation was 48 ± 23 HU in Group 1 and 39 ± 21 HU in Group 2 (P < 0.05). Overall signal to noise ratio was 15.6 ± 4.7 in Group 1 and 21.2 ± 7.7 in Group 2 (P < 0.01). CONCLUSION: Higher intra-vascular attenuation modifies significantly the attenuation of non-calcified coronary plaques. This results in a more difficult characterization between lipid rich vs fibrous type.

Coronary artery calcium score on low-dose computed tomography for lung cancer screening

AIM: To evaluate the feasibility of coronary artery calcium score(CACS) on low-dose non-gated chest CT(ngCCT).METHODS: Sixty consecutive individuals(30 males; 73 ± 7 years) scheduled for risk stratification by means of unenhanced ECG-triggered cardiac computed to-mography(gCCT) underwent additional unenhanced ngCCT. All CT scans were performed on a 64-slice CT scanner(Somatom Sensation 64 Cardiac, Siemens, Germany). CACS was calculated using conventional methods/scores(Volume, Mass, Agatston) as previ-ously described in literature. The CACS value obtained were compared. The Mayo Clinic classification was used to stratify cardiovascular risk based on Agatston CACS. Differences and correlations between the two methods were compared. A P-value < 0.05 was considered sig-nificant.RESULTS: Mean CACS values were significantly higher for gCCT as compared to ngCCT(Volume: 418 ± 747 vs 332 ± 597; Mass: 89 ± 151 vs 78 ± 141; Agatston: 481 ± 854 vs 428 ± 776; P < 0.05). The correlation between the two values was always very high(Volume: r = 0.95; Mass: r = 0.97; Agatston: r = 0.98). Of the 6 patients with 0 Agatston score on gCCT, 2(33%) showed an Agatston score > 0 in the ngCCT. Of the 3 patients with 1-10 Agatston score on gCCT, 1(33%) showed an Agatston score of 0 in the ngCCT. Overall, 23(38%) patients were reclassified in a different car-diovascular risk category, mostly(18/23; 78%) shifting to a lower risk in the ngCCT. The estimated radiation dose was significantly higher for gCCT(DLP 115.8 ± 50.7 vs 83.8 ± 16.3; Effective dose 1.6 ± 0.7 mSv vs 1.2 ± 0.2 mSv; P < 0.01).CONCLUSION: CACS assessment is feasible on ngCCT; the variability of CACS values and the associated re-stratification of patients in cardiovascular risk groups should be taken into account.

Levodopa/Carbidopa Intestinal Gel for Treatment of Advanced Parkinson’s Disease: An Update on the Effects of Cognitive Functions

Cognitive impairment is a frequent non-motorsymptom of Parkinson’s disease (PD). In early disease stage, this takes the features of dysexecutive syndrome, and is mostly dependent on derangement of frontostriatal circuitries. In advanced stages, worsening of dysexecutive symptoms is accompanied by disorientation and memory deficit leading to dementia in 30% of cases, due to multiple neurotransmitter derangement. Dysexecutive symptoms in the early stages of PD may benefit from dopamine replacement therapy (DRT). Conversely, severe cognitive symptoms in more advanced stages are frequently aggravated by DRT. In particular, pulsatile stimulation of dopaminergic receptors by orally administered levodopa (LD) plays a significant negative role on cognitive and neuropsychiatric symptoms in advanced PD. The introduction of a gel of LD-carbidopa for continuous intestinal administration (LCIG) allows marked stabilization of plasma LD concentrations and provides benefit on motor fluctuations and dyskinesia of significantly greater magnitude than conventional oral administration in advanced PD patients. The results from several preliminary studies suggest that efficacy of LCGI on motor symptoms may be accompanied by good tolerability and potential benefit on several non-motor symptoms, including cognitive impairment. Future studies with longer observation period and larger cohorts are advised to confirm these preliminary observations.

Validation of the Italian translation of the perceived stigma scale and resilience assessment in inflammatory bowel disease patients

BACKGROUND Stigmatization is the separation of an individual from a group due to aspects that make them different.Resilience may in turn influence the perception of stigma.Patients with inflammatory bowel disease(IBD)are susceptible to stigma,although data are very limited.AIM To validate an Italian translation of the IBD perceived stigma scale(PSS)in relation to patients’resilience.METHODS Consecutive IBD outpatients were prospectively enrolled(December 2018-September 2019)in an Italian,tertiary referral,IBD center.Clinical and demographic data were collected.Stigma and resilience were evaluated through the IBD-PSS and the 25-item Connor-Davidson Resilience Scale,respectively.The International Quality of Life Assessment Project approach was followed to translate the IBD-PSS into Italian and to establish data quality.Higher scores represent greater perceived stigma and resilience.Multivariable analysis for factors associated with greater stigma was computed.RESULTS Overall,126 IBD patients(mean age 46.1±16.9)were enrolled.The International Quality of Life Assessment criteria for acceptable psychometric properties of the scale were satisfied,with optimal data completeness.There was no ceiling effect,whilst floor effect was present(7.1%).The discriminant validity and the internal consistency reliability were good(Cronbach alpha=0.87).The overall internal consistency was 95%,and the test-retest reliability was excellent 0.996.The median PSS score was 0.45(0.20-0.85).Resilience negatively correlated with perceived stigma(Spearman’s correlation=-0.18,95%confidence intervals:-0.42-0.08,P=0.03).CONCLUSION We herein validated the Italian translation of the PSS scale,also demonstrating that resilience negatively impacts perceived stigma.

Mental health support to staff in a major hospital in Milan(Italy)during the COVID-19 pandemic:a framework of actions

To the Editor,As of 31 M arch 2020,m ore than 100000 cases of coronavirus disease 2019(COVID-19)have been confirm ed in Italy.1 Progressive mitigation measures have been introduced by the Italian governm ent since 9 M arch 2020 to underm ine and break the virus transmission chain.However,the COVID-19-associated hospitalisation rate in Lombardy,the epicentre of the outbreak,has risen since the late days o f February 2020,by 30%each day,and it is only very recently that it slowed down to 5%daily,which still translates to 500 new patients every day who are in absolute need of hospital care.

Automated weaning from mechanical ventilation

Mechanical ventilation(MV)is one of the lifesaving techniques applied to critically ill patients at bedside.However,some complications,such as ventilator-induced lung injury and ventilator-associated pneumonia,may occur in a patient undertaking MV and are often related to the duration of MV.Some written protocols have been proposed to reduce the risk of such complications,but they can be time consuming,leading to fluctuation in protocol implementation and compliance.Moreover,written instructions tend to be general and thus cannot cover all possible scenarios,resulting in variable interpretation of the protocol.To overcome these limiting factors,protocols have been computerized and there is convincing evidence in the literature showing that computerized protocols benefit management of the process and reduce the time a patient spends under MV.QuickWean is a computeraided weaning protocol implemented on the Hamilton S1 ventilator(Hamilton Medical AG,Bonaduz,Switzerland),which guides the patient through the weaning process without requiring any intervention by the treating physician.The fully-automated ventilation mode is INTELLiVENT?-ASV(Hamilton Medical AG),which is set according to the patient’s respiratory mechanics,patientventilator interaction,peripheral oxygen saturation(SpO2)and pulmonary end-tidal carbon dioxide(PetCO2).The INTELLiVENT?-ASV mode sets automatically each minute to provide accurate ventilation,pressure support,fraction of inspired oxygen and positive end-expiratory pressure based on the patient’s needs.QuickWean can be pre-set to match the established weaning policy of an intensive care unit as well as being customized to a patient’s needs.It provides a progressive reduction of respiratory support,and guides the patient through the spontaneous breathing trial(SBT).At the end of the SBT,the ventilator re-starts the previous ventilation support and provides a report of the successful SBT.During all phases,PetCO2,SpO2 and all breathing parameters are monitored.This new automated weaning tool may improve the safety and effectiveness of an SBT,reducing the time spent in the process of weaning and providing a lower workload for the treating physician.

Immunomodulation with rabbit anti-thymocyte globulin in solid organ transplantation

Rabbit anti-thymocyte globulin's manifold mechanisms of action may be attribuited to its polyclonal nature. Its T-cell depleting effect on lymphoid cells is well established: Occurring in the blood and secondary lymphoid tissues, depletion proceeds through complement-dependent lysis, opsonization and apoptotic pathways. Clinical studies have shown that rabbit antithymocyte globulin's immunomodulatory effect extends beyond the initial T-cell depletion and up to the period during which lymphocyte populations begin to recover. The drug is able to mediate immunomodulation and graft tolerance by functionally inactivating cell surface receptors involved in antigen recognition, leukocyte trafficking and leukocyte endothelium adhesion. The complex and prolonged immunomodulation induced by this drug contributes to its efficacy in solid organ transplantation, mainly by reducing the incidence of acute graft rejection.

Immune Activation in HIV-Infected Patients Treated with Different ARV Regimens

Objectives: To evaluate the effects of starting therapy with either Truvada (TVD) or Combivir (CBV) in combination with Efavirenz (EFV) or a boosted Protease Inhibitor (LPV/r, ATV/r, fAPV/r and SQV/r) on clinical, immunological, and virological parameters in HIV-infected antiretroviral (ARV) naive patients. Methods: Twenty-seven patients were prospectively enrolled and received TVD-EFV, 32 TVD-PI/r, 24 CBV-EFV, and 23 CBV-PI/r. Immunovirological analyses were performed at baseline and after 3, 6, 9 and 12 months after initiation of therapy;a full set of data is available for 51 patients. Results: Median CD4+ cell counts and HIV-RNA plasma viremia were comparable in the four groups of patients (TVD-EFV, TVD-PI/r, CBV-EFV, CBV-PI/r) at baseline. At month 12 HIV RNA plasma viremia was <50 cps/ml in all patients. Median CD4 cell counts increases were higher, although not significantly, in CBV-EFV and TVD-EFV patients. Finally, CD8+/CD38+/CDRO+T lymphocytes were significantly decreased after 12 months of therapy in all patients with, possibly, a faster effect seen in the EFV groups. Conclusions: Immunologic parameters are similarly affected by different ARV combinations, even if EFV-associated immunomodulation might be marginally better.

小胶质细胞控制成年小鼠海马中的谷氨酸能突触

小胶质细胞是调节大脑突触发育和可塑性的重要细胞类型,但其影响突触的正常功能的机制尚不清楚。在本研究中,我们通过PLX5622造成小胶质细胞耗竭,并观察其对成年野生型小鼠海马CA3-CA1突触的影响。在小胶质细胞耗竭后,与树突棘密度降低相关的自发和诱发谷氨酸能活动的减少,出现未成熟突触特征以及突触的可塑性提高。小胶质细胞耗竭的小鼠在新物体识别任务的获取方面表现出缺陷。海马星形胶质细胞出现增生,但并没有神经炎症反应。在Cx3cr1-/-小鼠中,PLX不能导致海马出现上述改变。这说明CX3CL1/CX3CR1轴在小胶质细胞对突触功能的控制中有重要作用。PLX5622停用后,小胶质细胞的重新增殖,海马突触恢复,小鼠的学习功能也出现恢复。综上所述,小胶质细胞对维持成人大脑的突触的正常功能用重要的作用,去除小胶质细胞会导致谷氨酸能突触组织和活动的可逆变化。

Loss of homeostatic functions in microglia from a murine model of Friedreich's ataxia

Friedreich's ataxia(FRDA)is a rare genetic disorder characterized by motor discoordination and cerebellar involvement due to mutations in the frataxin(FXN)gene,which encodes a mitochondrial protein involved in ironsulfur cluster biogenesis and iron handling."While progress has been made in understanding FRDA's pathophysiology and cerebellar degeneration caused by frataxin deficiency,the role of central nervous system(CNS)-resident nonneuronal cells,as microglia,necessitates further investigation.

Is it worth already in the first step exceeding the 3-g protein limit for the oral food challenge for food protein-induced enterocolitis syndrome?

To the editor:Food protein-induced enterocolitis syndrome(FPIES)is a non-immunoglobulin E-mediated food allergy that is characterized by repetitive vomiting within 1-4 h of eating the trigger food and may be associated with lethargy,pallor,and diarrhea.The diagnosis is in most cases anamnestic.1 In a few cases,it is necessary to perform the oral food challenge(OFC).

Mirror,mirror on the wall,who is the best of them all?Artificial intelligence versus gastroenterologists in solving clinical problems

Introduction Artificial intelligence(AI)is a concept that commonly refers to machines mimicking human cognitive behavior during learning and problem-solving[1].Chatbots are a typical example of an AI system,capable of interacting with humans[2].ChatGPT(OpenAI,San Francisco,CA,USA)[3]is a new-generation chatbot that captures the context and relationship between words in input sequences through multiple layers of self-attention and feedforward neural networks.Then,it predicts the most likely“token”to succeed the previous one based on patterns in its training data.Therefore,it is a self-contained system that does not copy existing information[4].

Heavy cigarette smoking and alcohol consumption are associated with impaired sperm parameters in primary infertile men

We assessed the concomitant impact of cigarette smoking and alcohol con sumption in men presenting for primary couple's infertility.Data from 189 in fertile men were an a lyzed.Semen analysis,serum hormones,and sperm DNA fragmentation(SDF)were obtained.Smoking status was categorized as follows:current nonsmoker(-S),moderate smoker(+MS),and heavy smoker(+HS).Alcohol consumption was categorized as follows:abstainer(-D),moderate drinker(+MD),and heavy drinker(+HD).Descriptive statistics and logistic regression models were applied.Among all the participants,132(69.8%),30(15.9%),and 27(14.3%)patients were-S,+MS,and+HS,respectively.In addition,67(35.4%),77(40.7%)and 45(23.8%)men were-D,+MD and+HD,respectively.Regarding concomitant habits,52(27.5%)patients were nonsmokers and abstainers(-S/-D:Group 1),91(48.1%)had at least one recreational habit(-S/+D or+S/-D:Group 2),and 46(24.3%)were both smokers and drinkers(+S/+D:Group 3).Sperm concentration and progressive motility were lower in+HS and+HD,compared with-S and-D(all P<0.05),respectively.Similarly,both parameters were significantly lower in Group 3 than Groups 1 and 2(all P<0.05).SDF values were higher in Group 3 than Groups 1 and 2(both P<0.05).In multivariate analysis,follicle-stimulating hormone(FSH)levels and concomitant+S/+D status were independent predictors of impaired sperm concentration and progressive motility(all P<0.05).Heavy smoking and heavy drinking were associated with worse seminal parameters than moderate smoking/drinking and nonsmoking/abstaining.When concomitant,+S/+D status has an even greater detrimental effect on semen parameters.

Substances of abuse consumption among patients seeking medical help for uro-andrological purposes:a sociobehavioral survey in the real-life scenario

Substances of abuse(SoA),as well as smoking and alcohol consumption,are well known for their impact on male fertility status,erectile function,and ejaculation.We assessed SoA consumption habits in a cohort of men seeking medical attention for uro-andrological purposes.Data from 7447 men seeking medical attention for the first time for uro-andrological purposes were analyzed.A complete medical and sexual history was collected for each patient.Smoking,alcohol,and SoA consumption were investigated.Descriptive statistics was used to describe the whole cohort.The primary motivations for their evaluation were lower urinary tract symptoms(LUTS),erectile dysfunction(ED),and infertility in 1912(25.7%),2944(39.5%),and 2591(34.8%)men,respectively.Previous use of SoA was reported by 378(5.1%)men,and 190(2.6%)individuals were current users.Patients seeking medical attention for infertility were more frequently current SoA users(107;4.1%)than men with ED(66;2.2%)and LUTS(17;0.9%)(both P<0.001).Current users of SoA were younger than those with past or no SoA history(P<0.001).Current SoA users were more frequently smokers(P<0.001)and alcohol consumers(P<0.001)than those with a previous history or those who had never tried SoA.In conclusion,approximately 3%of men seeking medical attention for uro-andrological purposes were current SoA consumers.Infertile men reported a higher use of SoA than those with ED or LUTS.Current SoA users were younger and more frequently concomitant smokers and alcohol consumers compared to those who did or had never used SoA.

The precision and agreement of corneal thickness and keratometry measurements with SS-OCT versus Scheimpflug imaging

Purpose:To assess the repeatability and reproducibility of swept-source optical coherence tomography(SS-OCT)and Scheimpflug system and evaluate the agreement between the two systems in measuring multiple corneal regions in children.Methods:Pachymetric and keratometric maps for both systems were evaluated.Central,midperipheral and peripheral corneal thickness(CT),keratometry and astigmatism power vectors were recorded.The three outcomes yielded by the same observer were used to assess intraobserver repeatability.The differences in the mean values provided by each observer were used to evaluate interobserver reproducibility.Within-subject standard deviation,test-retest repeatability(TRT)and coefficient of variation(CoV)were used to analyze the intraobserver repeatability and interobserver reproducibility.Paired T-test and Bland-Altman were used to appraise interdevice agreement.Results:Seventy-eight eyes of 78 children were included.The CoV was≤2.12 and 1.10%,respectively,for repeatability and reproducibility.TRT and CoV were lower for central and paracentral CT measurements than for peripheral measurements.The SS-OCT device generated higher precision when acquiring CT data,whereas Scheimpflug system showed higher reliability when measuring corneal keratometry.Although the CT readings measured using SS-OCT were significantly thinner than Scheimpflug device(P<0.001),the central and thinnest CT values were still of high agreement.The interdevice agreement of keratometry measurement was high for the central corneal region and moderate for the paracentral and peripheral areas.Conclusions:The precision of CT measurements by SS-OCT was higher,while the reliability of keratometry measurements by the Scheimpflug system was higher in children.Apart from the measured values in the central corneal region,the thickness and keratometry readings should not be considered interchangeable between the two systems.

Effect of orthokeratology on precision and agreement assessment of a new sweptsource optical coherence tomography biometer

Background:To evaluate the effect of orthokeratology on precision of measurements in children using a new swept-source optical coherence tomography(SS-OCT)optical biometer(OA-2000),and agreement between its measurements and those provided by the commonly used IOLMaster based on partial coherence interferometry(PCI).Methods:This study recruited fifty-one eyes of 51 normal children(8–16 years).An operator took measurements with the two biometers.Then,a second operator took measurements with the SS-OCT biometer.After orthokeratology was performed for one month,the same operators repeated the same procedures.Axial length(AL),mean keratometry(Km)at 2.5 mm and 3.0 mm diameters(Km2.5 and Km3.0),central corneal thickness(CCT),anterior chamber depth(ACD),lens thickness(LT)and corneal diameter(CD)were analyzed.Results:With the SS-OCT optical biometer,the test-retest repeatability of AL measurements was<0.06 mm.For all parameters,the coefficients of variation were<1.23%and the intraclass correlation coefficients were>0.95.The 95%limits of agreement of difference between the two devices for CD parameter were up to 1.53 mm.After orthokeratology,the fluctuation ranges of difference for Km3.0 measurement was 1.11 times higher than before orthokeratology,while the absolute values of difference for AL,Km2.5,ACD and CD measurements were comparable.Conclusions:Before and after orthokeratology,the SS-OCT biometer showed high repeatability and reproducibility for all measurements.Wearing orthokeratology contact lenses affected the agreement between SS-OCT and PCI biometers for Km3.0 measurements.The CD measurement showed poor agreement between the two devices.