期刊,Journal of Internal Medicine 2022年292卷1期_国家学术搜索

期刊信息/Journal information

Journal of Internal Medicine

Blackwell Scientific Publications

主办单位：Blackwell Scientific Publications

国际刊号：0954-6820

Journal of Internal Medicine/Journal Journal of Internal MedicineSCIISTP

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1页

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SYMPOSIUM: 17th Key Symposium: Blood‐Brain Barrier: Key to Brain Health and Disease

1页

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The influence of the blood–brain barrier in the treatment of brain tumours

Sneha RathiJessica I. GriffithWenjuan ZhangWenqiu Zhang...

28页

查看更多>>摘要：Abstract Brain tumours have a poor prognosis and lack effective treatments. The blood–brain barrier (BBB) represents a major hurdle to drug delivery to brain tumours. In some locations in the tumour, the BBB may be disrupted to form the blood–brain tumour barrier (BBTB). This leaky BBTB enables diagnosis of brain tumours by contrast enhanced magnetic resonance imaging; however, this disruption is heterogeneous throughout the tumour. Thus, relying on the disrupted BBTB for achieving effective drug concentrations in brain tumours has met with little clinical success. Because of this, it would be beneficial to design drugs and drug delivery strategies to overcome the ‘normal’ BBB to effectively treat the brain tumours. In this review, we discuss the role of BBB/BBTB in brain tumour diagnosis and treatment highlighting the heterogeneity of the BBTB. We also discuss various strategies to improve drug delivery across the BBB/BBTB to treat both primary and metastatic brain tumours. Recognizing that the BBB represents a critical determinant of drug efficacy in central nervous system tumours will allow a more rapid translation from basic science to clinical application. A more complete understanding of the factors, such as BBB–limited drug delivery, that have hindered progress in treating both primary and metastatic brain tumours, is necessary to develop more effective therapies.

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Developmental regulation of barrier‐ and non‐barrier blood vessels in the CNS

A. Ben‐ZviS. Liebner

16页

查看更多>>摘要：Abstract The blood–brain barrier (BBB) is essential for creating and maintaining tissue homeostasis in the central nervous system (CNS), which is key for proper neuronal function. In most vertebrates, the BBB is localized to microvascular endothelial cells that acquire barrier properties during angiogenesis of the neuroectoderm. Complex and continuous tight junctions, and the lack of fenestrae combined with low pinocytotic activity render the BBB endothelium a tight barrier for water‐soluble molecules that may only enter the CNS via specific transporters. The differentiation of these unique endothelial properties during embryonic development is initiated by endothelial‐specific flavours of the Wnt/β‐catenin pathway in a precise spatiotemporal manner. In this review, we summarize the currently known cellular (neural precursor and endothelial cells) and molecular (VEGF and Wnt/β‐catenin) mechanisms mediating brain angiogenesis and barrier formation. Moreover, we introduce more recently discovered crosstalk with cellular and acellular elements within the developing CNS such as the extracellular matrix. We discuss recent insights into the downstream molecular mechanisms of Wnt/β‐catenin in particular, the recently identified target genes like Foxf2, Foxl2, Foxq1, Lef1, Ppard, Zfp551, Zic3, Sox17, Apcdd1 and Fgfbp1 that are involved in refining and maintaining barrier characteristics in the mature BBB endothelium. Additionally, we elute to recent insight into barrier heterogeneity and differential endothelial barrier properties within the CNS, focussing on the circumventricular organs as well as on the neurogenic niches in the subventricular zone and the hippocampus. Finally, open questions and future BBB research directions are highlighted in the context of taking benefit from understanding BBB development for strategies to modulate BBB function under pathological conditions.

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Central nervous system zoning: How brain barriers establish subdivisions for CNS immune privilege and immune surveillance

Steven T. ProulxBritta Engelhardt

21页

查看更多>>摘要：Abstract The central nervous system (CNS) coordinates all our body functions. Neurons in the CNS parenchyma achieve this computational task by high speed communication via electrical and chemical signals and thus rely on a strictly regulated homeostatic environment, which does not tolerate uncontrolled entry of blood components including immune cells. The CNS thus has a unique relationship with the immune system known as CNS immune privilege. Previously ascribed to the presence of blood–brain barriers and the lack of lymphatic vessels in the CNS parenchyma prohibiting, respectively, efferent and afferent connections with the peripheral immune system, it is now appreciated that CNS immune surveillance is ensured by cellular and acellular brain barriers that limit immune cell and mediator accessibility to specific compartments at the borders of the CNS. CNS immune privilege is established by a brain barriers anatomy resembling the architecture of a medieval castle surrounded by two walls bordering a castle moat. Built for protection and defense this two‐walled rampart at the outer perimeter of the CNS parenchyma allows for accommodation of different immune cell subsets and efficient monitoring of potential danger signals derived from inside or outside of the CNS parenchyma. It enables effective mounting of immune responses within the subarachnoid or perivascular spaces, while leaving the CNS parenchyma relatively undisturbed. In this study, we propose that CNS immune privilege rests on the proper function of the brain barriers, which allow for CNS immune surveillance but prohibit activation of immune responses from the CNS parenchyma unless it is directly injured.

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Low‐dose computed tomography lung cancer screening: Clinical evidence and implementation research

Harriet L. LancasterMarjolein A. HeuvelmansMatthijs Oudkerk

13页

查看更多>>摘要：Abstract Lung cancer causes more deaths than breast, cervical, and colorectal cancer combined. Nevertheless, population‐based lung cancer screening is still not considered standard practice in most countries worldwide. Early lung cancer detection leads to better survival outcomes: patients diagnosed with stage 1A lung cancer have a >75% 5‐year survival rate, compared to <5% at stage 4. Low‐dose computed tomography (LDCT) thorax imaging for the secondary prevention of lung cancer has been studied at length, and has been shown to significantly reduce lung cancer mortality in high‐risk populations. The US National Lung Screening Trial reported a 20% overall reduction in lung cancer mortality when comparing LDCT to chest X‐ray, and the Nederlands‐Leuvens Longkanker Screenings Onderzoek (NELSON) trial more recently reported a 24% reduction when comparing LDCT to no screening. Hence, the focus has now shifted to implementation research. Consequently, the 4‐IN‐THE‐LUNG‐RUN consortium based in five European countries, has set up a large‐scale multicenter implementation trial. Successful implementation of and accessibility to LDCT lung cancer screening are dependent on many factors, not limited to population selection, recruitment strategy, computed tomography screening frequency, lung‐nodule management, participant compliance, and cost effectiveness. This review provides an overview of current evidence for LDCT lung cancer screening, and draws attention to major factors that need to be addressed to successfully implement standardized, effective, and accessible screening throughout Europe. Evidence shows that through the appropriate use of risk‐prediction models and a more personalized approach to screening, efficacy could be improved. Furthermore, extending the screening interval for low‐risk individuals to reduce costs and associated harms is a possibility, and through the use of volumetric‐based measurement and follow‐up, false positive results can be greatly reduced. Finally, smoking cessation programs could be a valuable addition to screening programs and artificial intelligence could offer a solution to the added workload pressures radiologists are facing.

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Wiley

Advances in the Omicron variant development

Antonio VitielloFrancesco FerraraAmogh M. AutiMarina Di Domenico...

10页

查看更多>>摘要：Abstract Severe acute respiratory syndrome coronavirus (SARS‐CoV)‐2 has spread worldwide, leading the World Health Organization (WHO) to declare a pandemic, on 11 March 2020. Variants of concern have appeared at regular intervals—Alpha, Beta, Gamma, Delta, and now Omicron. Omicron variant, first identified in Botswana in November 2021, is rapidly becoming the dominant circulating variant. In this review, we provide an overview regarding the molecular profile of the Omicron variant, epidemiology, transmissibility, the impact on vaccines, as well as vaccine escape, and finally, we report the pharmacological agents able to block the endocellular entry of SARS‐CoV‐2 or to inhibit its viral replication. The Omicron has more than 50 mutations, of which the spike protein has 26–35 amino acids different from the original SARS‐CoV‐2 virus or the Delta, some of which are associated with humoral immune escape potential and greater transmissibility. Omicron has a significant growth advantage over Delta, leading to rapid spread with higher incidence levels. The disease so far has been mild compared to the Delta. The two vaccination doses offer little or no protection against Omicron infection while the booster doses provide significant protection against mild illness and likely offer even greater levels of protection against serious illness. Recently, new oral antiviral agents such as molnupiravir and paxlovid have been approved and represent important therapeutic alternatives to antiviral remdesivir. In addition, monoclonal antibodies such as casirivimab/imdevimab bind different epitopes of the spike protein receptor; is this class of drugs effective against the Omicron variant? However, more research is needed to define whether Omicron is indeed more infectious and whether the vaccines, monoclonal antibodies, and antivirals currently available are effective.

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Wiley

Prediction of new organ onset in recurrent immunoglobulin G4–related disease during 10?years of follow‐up

Shuang ZhouCan HuangMu WangLiang Zhu...

12页

查看更多>>摘要：Abstract Objective Frequent relapse is a prominent challenge in managing immunoglobulin G4–related disease (IgG4‐RD). According to the types of organs involved in relapse, relapse patterns were divided into recurrent organ involvement (ROI) and new organ involvement (NOI). We aimed to investigate the discrepancy in clinical relapse patterns and establish an effective prognostic nomogram for NOI. Methods We retrospectively enrolled 125 IgG4‐RD patients who experienced relapse during the follow‐up period. Patients were classified into two groups: those with NOI (including NOI and NOI?+?ROI) and without NOI (ROI). Logistic regression analyses were used to assess the risk factors for NOI. The results were externally validated by a separate prospective cohort of 39 patients with relapse. Results There were 81 (64.8%) and 44 (35.2%) patients without NOI and with NOI, respectively. Patients without NOI showed higher baseline disease activity. The most common ROIs were the lacrimal gland and submandibular gland, while the lung and urinary system were the most involved in NOI. Re‐elevation of serum IgG4 level to 74.31% of baseline was associated with NOI. Multiple relapses, organ involvement type at baseline, glucocorticoids combined with immunosuppressive drugs (IM) or IM alone during the maintenance period, and relapse IgG4/baseline IgG4 ratio were included in the nomogram. Both internal and external validations showed good agreement and discrimination. Conclusions About one third of IgG4‐RD patients with relapse suffer from NOI. We developed a risk stratification model that can effectively predict the future risk of NOI. Glucocorticoid and IM combined therapy during maintenance is also recommended.

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One‐year persistent symptoms and functional impairment in SARS‐CoV‐2 positive and negative individuals

Mayssam NehmeOlivia BraillardFran?ois ChappuisDelphine S. Courvoisier...

13页

查看更多>>摘要：Abstract Background Persistent symptoms of SARS‐CoV‐2 are prevalent weeks to months following the infection. To date, it is difficult to disentangle the direct from the indirect effects of SARS‐CoV‐2, including lockdown, social, and economic factors. Objective The study aims to characterize the prevalence of symptoms, functional capacity, and quality of life at 12 months in outpatient symptomatic individuals tested positive for SARS‐CoV‐2 compared to individuals tested negative. Methods From 23 April to 27 July 2021, outpatient symptomatic individuals tested for SARS‐CoV‐2 at the Geneva University Hospitals were followed up 12 months after their test date. Results At 12 months, out of the 1447 participants (mean age 45.2 years, 61.2% women), 33.4% reported residual mild to moderate symptoms following SARS‐CoV‐2 infection compared to 6.5% in the control group. Symptoms included fatigue (16% vs. 3.1%), dyspnea (8.9% vs. 1.1%), headache (9.8% vs. 1.7%), insomnia (8.9% vs. 2.7%), and difficulty concentrating (7.4% vs. 2.5%). When compared to the control group, 30.5% of SARS‐CoV‐2 positive individuals reported functional impairment at 12 months versus 6.6%. SARS‐CoV‐2 infection was associated with the persistence of symptoms (adjusted odds ratio [aOR] 4.1; 2.60–6.83) and functional impairment (aOR 3.54; 2.16–5.80) overall, and in subgroups of women, men, individuals younger than 40 years, those between 40–59 years, and in individuals with no past medical or psychiatric history. Conclusion SARS‐CoV‐2 infection leads to persistent symptoms over several months, including in young healthy individuals, in addition to the pandemic effects, and potentially more than other common respiratory infections. Symptoms impact functional capacity up to 12 months post infection.

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Wiley

Management and prognosis of HIV‐associated pulmonary arterial hypertension: 20 Years of evidence from the REHAP registry

María Lázaro SalvadorLuis Rodríguez‐PadialClara Soto AbánadesAlejandro Cruz Utrilla...

11页

查看更多>>摘要：Abstract Background Pulmonary arterial hypertension (PAH) is an independent predictor of death in patients with human immunodeficiency virus (HIV) infection. HIV is the leading cause of PAH (HIV‐PAH) worldwide. Aims We described the characteristics, treatment patterns, and prognosis of a cohort of HIV‐PAH patients and compared them with those of an equivalent cohort of patients with idiopathic/familial PAH (IPAH/FPAH). Methods We retrospectively analysed and compared the demographic, clinical, and treatment data from patients with HIV‐PAH and those with IPAH/FPAH in the Spanish PAH registry (REHAP) from 1998 to 2018. The HIV‐PAH overall survival (OS) rate up to 5 years was compared to the age‐ and sex‐matched IPAH/FPAH population. Changes in treatment patterns in patients with HIV‐PAH after 2010 and their effects on OS were also analysed. Results Compared to those with IPAH/FPAH (n = 739), patients with HIV‐PAH (n = 132) were younger, mainly men, and had a better functional status. The clinical presentation, haemodynamics, and respiratory function were similar between the groups. Parenteral drug use was the most common mode of HIV transmission. Approximately 11% of patients with HIV‐PAH did not receive PAH‐targeted therapy. The age‐ and sex‐adjusted 5‐year OS rate from diagnosis was 74.0% for patients with HIV‐PAH and 68.7% for those with IPAH (p < 0.159). During/after 2010, 23% of patients with IPAH/FPAH received upfront dual oral combination, while oral monotherapy remained the main first‐line treatment in patients with HIV‐PAH. The overall OS rate remained stable. Conclusions Patients with HIV‐PAH were predominantly young men. The short‐term prognosis is similar to that of age‐ and sex‐matched patients with IPAH/FPAH, despite a better functional status. Oral monotherapy remains the preferred first‐line treatment in the current cohorts.

原文链接:

NSTL
Wiley