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The interplay of drug therapeutics and immune responses to SARS-CoV-2

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Cellular & Molecular Immunology 2024年第2期21卷 197-200页

作者： valeria Fumagalli Matteo Iannacone Division of Immunology Transplantationand Infectious DiseasesIRCCS San Raffaele Scientific InstituteMilanItaly Vita-Salute San Raffaele University MilanItaly Experimental Imaging Centre IRCCS San Raffaele Scientific InstituteMilanItaly

The SARS-CoV-2 pandemic has necessitated rapid therapeutic and preventative responses.While vaccines form the frontline of defense,antiviral treatments such as nirmatrelvir have emerged as vital adjunctive measures,particularly for those unable or unwilling to be vaccinated.This review delves into the potential influence of nirmatrelvir on enduring immunity.In parallel,the potential of drug repurposing is explored,with bisphosphonates being examined for their possible effects against COVID-19 due to their immunomodulatory properties.The importance of rigorous clinical trials and careful interpretation of preliminary data is emphasized.

关键词： SARS-CoV-2 Nirmatrelvir Bisphosphonates Adaptive immunity Drug repurposing

Why is early detection of colon cancer still not possible in 2023?

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World Journal of Gastroenterology 2024年第3期30卷 211-224页

作者： valeria Tonini Manuel Zanni Department of Medical and Surgical Sciences University of BolognaBologna 40138Italy

Colorectal cancer(CRC)screening is a fundamental tool in the prevention and early detection of one of the most prevalent and lethal cancers.Over the years,screening,particularly in those settings where it is well organized,has succeeded in reducing the incidence of colon and rectal cancer and improving the prognosis related to them.Despite considerable advancements in screening technologies and strategies,the effectiveness of CRC screening programs remains less than optimal.This paper examined the multifaceted reasons behind the persistent lack of effect-iveness in CRC screening initiatives.Through a critical analysis of current methodologies,technological limitations,patient-related factors,and systemic challenges,we elucidated the complex interplay that hampers the successful reduction of CRC morbidity and mortality rates.While acknowledging the ad-vancements that have improved aspects of screening,we emphasized the necessity of addressing the identified barriers comprehensively.This study aimed to raise awareness of how important CRC screening is in reducing costs for this disease.Screening and early diagnosis are not only important in improving the prognosis of patients with CRC but can lead to an important reduction in the cost of treating a disease that is often diagnosed at an advanced stage.Spending more sooner can mean saving money later.

关键词： Colorectal cancer Colorectal cancer screening Colorectal screening test Colon and rectal cancer

How to identify early complications in patients undergoing distal gastrectomy?

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 974-981页

作者： Giuseppe Tropeano Maria Michela Chiarello valeria Fico Giuseppe Brisinda Emergency Surgery and Trauma Center Fondazione Policlinico Universitario A Gemelli IRCCSRome 00168Italy Department of Surgery Azienda Sanitaria Provinciale di CosenzaCosenza 87100Italy Department of Medical and Surgical Sciences UniversitàCattolica del Sacro CuoreRome 00168Italy

In this editorial we comment on the article by Zhang et al published in a recent issue of the World Journal of Gastrointestinal Surgery.Gastrectomy with appropriate lymph node dissection is still standard curative treatment in locally advanced gastric cancer.Several studies point out that gastric cancer surgery is a complex procedure that leads to a high risk of morbidity and mortality.Many factors can contribute to the onset of complications with consequent effects on prognosis and increased mortality.The complications can be divided in complications related to anastomosis,to motility and to surgical site infection.The study presented by Zhang B et al represent an interesting analysis on the possibility to prevent postoperative morbidity.The study was performed on 131 patients with distal gastric cancer who underwent gastrectomy with D2 lymph node dissection.Of these patients,16%developed early postoperative complications.The univariate analysis showed that prealbumin level,hypertension,diabetes,history of abdominal surgery,R0 resection,and blood transfusion were factors influencing early postoperative complications after distal gastrectomy.Moreover,the inclusion of the above significant variables in the logistic regression analysis revealed that hypertension,diabetes,a history of abdominal surgery,and blood transfusion were independent predictors of postoperative complications.In conclusion,preoperative and intraoperative factors can be used to establish an early postoperative nomogram model.The results of the study presented by Zhang et al suggest that the prediction model can be used to guide the detection of postoperative complications and has clinical reference value.

关键词： Gastric cancer Gastrectomy Lymph node dissection Morbidity Mortality Surgical site infections

Indocyanine green:The guide to safer and more effective surgery

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World Journal of Gastrointestinal Surgery 2024年第3期16卷 641-649页

作者： Pietro Fransvea Maria Michela Chiarello valeria Fico Maria Cariati Giuseppe Brisinda Emergency Surgery and Trauma Center Fondazione Policlinico Universitario Agostino Gemelli IRCCSRome 00168Italy Department of Surgery Azienda Sanitaria Provinciale di CosenzaCosenza 87100Italy Department of Surgery Azienda Sanitaria Provinciale di CrotoneCrotone 88900Italy Department of Abdominal and Endocrine Metabolic Medical and Surgical Sciences Fondazione Policlinico Universitario A Gemelli IRCCSRome 00168Italy

In this editorial we comment on the article by Kalayarasan and co-workers published in the recent issue of the World Journal of Gastrointestinal Surgery.The authors present an interesting review on the use of indocyanine green fluo-rescence in different aspects of abdominal surgery.They also highlight future perspectives of the use of indocyanine green in mini-invasive surgery.Indo-cyanine green,used for fluorescence imaging,has been approved by the Food and Drug Administration and is safe for use in humans.It can be administered in-travenously or intra-arterially.Since its advent,there have been several advance-ments in the applications of indocyanine green,especially in the surgical field,such as intraoperative mapping and biopsy of sentinel lymph node,measurement of hepatic function prior to resection,in neurosurgical cases to detect vascular anomalies,in cardiovascular cases for patency and assessment of vascular ab-normalities,in predicting healing following amputations,in helping visualization of hepatobiliary anatomy and blood vessels,in reconstructive surgery,to assess flap viability and for the evaluation of tissue perfusion following major trauma and burns.For these reasons,the intraoperative use of indocyanine green has become common in a variety of surgical specialties and transplant surgery.Co-lorectal surgery has just lately begun to adopt this technique,particularly for perfusion visualization to prevent anastomotic leakage.The regular use of in-docyanine green coupled with fluorescence angiography has recently been pro-posed as a feasible tool to help improve patient outcomes.Using the best available data,it has been shown that routine use of indocyanine green in colorectal surgery reduces the rates of anastomotic leak.The use of indocyanine green is proven to be safe,feasible,and effective in both elective and emergency scenarios.However,additional robust evidence from larger-scale,high-quality studies is essential before incorporating indocyanine green guided surgery into standard practice.

关键词： Indocyanine green Colorectal surgery Fluorescence-guided surgery Gastrointestinal surgery Hepato-biliary surgery Pancreatic surgery Surgical oncology

Hepatitis C virus eradication in people living with human immunodeficiency virus:Where are we now?

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World Journal of Hepatology 2024年第5期16卷 661-666页

作者： Anna Maria Spera Pasquale Pagliano valeria Conti Infectious Disease Unit Universitary Hospital OORR San Giovanni di Dio e Ruggi d'AragonaSalerno 84131Italy Department of Infectious Diseases University of SalernoSalerno 84131Italy Clinical Pharmacology and Pharmacogenetics Unit University Hospital“San Giovanni di Dio e Ruggi d’Aragona”Salerno 84131Italy

Hepatitis C virus(HCV)/human immunodeficiency virus(HIV)co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV,according to World Health Organization.People living with HIV(PLWH)are six times greater affected by HCV,compared to HIV negative ones;the greater prevalence is encountered among people who inject drugs and men who have sex with men:the risk of HCV transmission through sexual contact in this setting can be increased by HIV infection.These patients experience a high rate of chronic hepatitis,which if left untreated progresses to end-stage liver disease and hepato-cellular carcinoma(HCC)HIV infection increases the risk of mother to child vertical transmission of HCV.No vaccination against both infections is still available.There is an interplay between HIV and HCV infections.Treatment of HCV is nowadays based on direct acting antivirals(DAAs),HCV treatment plays a key role in limiting the progression of liver disease and reducing the risk of HCC development in mono-and coinfected individuals,especially when used at an early stage of fibrosis,reducing liver disease mortality and morbidity.Since the sustained virological response at week 12 rates were observed in PLWH after HCV eradication,the AASLD has revised its simplified HCV treatment algorithm to also include individuals living with HIV.HCV eradication can determine dyslipidemia,since HCV promotes changes in serum lipid profiles and may influence lipid metabolism.In addition to these apparent detrimental effects on the lipid profile,the efficacy of DAA in HCV/HIV patients needs to be considered in light of its effects on glucose metabolism mediated by improvements in liver function.The aim of the present editorial is to describe the advancement in HCV treatment among PLWH.

关键词： Hepatitis People living with human immunodeficiency virus Direct acting antivirals Highly active antiretroviral therapy Co-infection

Psychiatric outcomes in outpatients affected by long COVID:A link between mental health and persistence of olfactory complaint

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World Journal of Psychiatry 2024年第4期14卷 507-512页

作者： Victoria Metelkina-Fernandez Louise-Emilie Dumas Clair Vandersteen David Chirio Auriane Gros Arnaud Fernandez Florence Askenazy valeria Manera Department of Psychiatry Nice University HospitalNice 06000France Department of Child and Adolescent Psychiatry UniversitéCôte d’AzurNice 06200France ENT Head and Neck InstituteNice 06100France Department of Infectiology Nice University HospitalNice 06200France Department of Orthophony UniversitéCôte d’AzurNice 06100France Cobtek UniversitéCôte d’AzurNice 06100France

BACKGROUND Anosmia was one of the main symptoms of coronavirus disease 2019(COVID-19).A psychiatric history(i.e.,depression)may be an independent contributor to the risk of COVID-19 diagnosis,and COVID-19 survivors appear to have an increased risk of neuropsychiatric sequelae(bidirectional association).AIM To compare the rate of psychiatric disorder among post-COVID patients without anosmia vs patients with persistent olfactory complaints.METHODS We conducted a prospective case control study from March 2020 to May 2021.Patients recruited at the ENT department of Nice University Hospital had a subjective olfactory complaint(visual analogue scale)for over 6 wk and a molecular or CT-proven severe acute respiratory syndrome coronavirus 2 diagnosis confirmed by serology.Post-COVID patients without persistent olfactory disorders were recruited at the university hospital infectiology department.Psychiatric medical histories were collected by a psychiatrist during the assessments.RESULTS Thirty-four patients with post-COVID-19 olfactory complaints were included in the first group of the study.Fifty percent of the patients were female(n=17).The group’s mean age was 40.5±12.9 years.The control group included 32 participants,of which 34.4%were female(n=11),and had a mean age of 61.2±12.2 years.The rate of psychiatric disorder among post-COVID patients with olfactory complaints was significatively higher(41.7%)than among patients without(18.8%)(χ2=5.9,P=0.015).CONCLUSION The presence of a psychiatric history may constitute a potential risk factor for the development of long COVID due to persistent anosmia.It therefore seems important to establish reinforced health monitoring after a COVID 19 infection in at-risk patients.Further prospective,translational,and collaborative studies are needed to extrapolate these results to the general population.

关键词： COVID-19 Anosmia Psychiatry Stress Neuroplasticity Psychiatric history

Frequentist and Bayesian Sample Size Determination for Single-Arm Clinical Trials Based on a Binary Response Variable: A Shiny App to Implement Exact Methods

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Open Journal of Statistics 2024年第1期14卷 90-105页

作者： Susanna Gentile valeria Sambucini Department of Statistical Sciences Sapienza University of Rome Rome Italy

Sample size determination typically relies on a power analysis based on a frequentist conditional approach. This latter can be seen as a particular case of the two-priors approach, which allows to build four distinct power functions to select the optimal sample size. We revise this approach when the focus is on testing a single binomial proportion. We consider exact methods and introduce a conservative criterion to account for the typical non-monotonic behavior of the power functions, when dealing with discrete data. The main purpose of this paper is to present a Shiny App providing a user-friendly, interactive tool to apply these criteria. The app also provides specific tools to elicit the analysis and the design prior distributions, which are the core of the two-priors approach.

关键词： Binomial Proportion Frequentist and Bayesian Power Functions Exact Sample Size Determination Shiny App Two-Priors Approach

Highly sensitive ratiometric fluorescent fiber matrices for oxygen sensing with micrometer spatial resolution

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Bio-Design and Manufacturing 2024年第3期7卷 292-306页

作者： Giuliana Grasso Valentina Onesto Stefania Forciniti Eliana D’Amone Francesco Colella Lara Pierantoni valeria Famà Giuseppe Gigli Rui L.Reis J.Miguel Oliveira Loretta L.del Mercato nstitute of Nanotechnology National Research Council(CNR-NANOTEC)c/o Campus Ecoteknevia Monteroni73100 LecceItaly Department of Mathematics and Physics“Ennio De Giorgi” University of Salentoc/o Campus Ecoteknevia Monteroni73100 LecceItaly 3B’s Research Group I3Bs–Research Institute on BiomaterialsBiodegradables and BiomimeticsHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineUniversity of MinhoAveParkZona Industrial da Gandra4805-017 BarcoGuimarãesPortugal ICVS/3B’s-PT Government Associate Laboratory 4806-909 Braga/GuimarãesPortugal Department of Experimental Medicine University of Salentoc/o Campus Ecoteknevia Monteroni73100 LecceItaly

Oxygen(O_(2))-sensing matrices are promising tools for the live monitoring of extracellular O_(2) consumption levels in long-term cell cultures.In this study,ratiometric O_(2)-sensing membranes were prepared by electrospinning,an easy,low-cost,scalable,and robust method for fabricating nanofibers.Poly(ε-caprolactone)and poly(dimethyl)siloxane polymers were blended with tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II)dichloride,which was used as the O_(2)-sensing probe,and rhodamine B isothiocyanate,which was used as the reference dye.The functionalized scaffolds were morphologically characterized by scanning electron microscopy,and their physicochemical profiles were obtained by Fourier transform infrared spectroscopy,thermogravimetric analysis,and water contact angle measurement.The sensing capabilities were investigated by confocal laser scanning microscopy,performing photobleaching,reversibility,and calibration curve studies toward different dissolved O_(2)(DO)concentrations.Electrospun sensing nanofibers showed a high response to changes in DO concentrations in the physiological-pathological range from 0.5%to 20%and good stability under ratiometric imaging.In addition,the sensing systems were highly biocompatible for cell growth promoting adhesiveness and growth of three cancer cell lines,namely metastatic melanoma cell line SK-MEL2,breast cancer cell line MCF-7,and pancreatic ductal adenocarcinoma cell line Panc-1,thus recreating a suitable biological environment in vitro.These O_(2)-sensing biomaterials can potentially measure alterations in cell metabolism caused by changes in ambient O_(2)content during drug testing/validation and tissue regeneration processes.

关键词： Electrospinning Ruthenium(II)dichloride Oxygen sensors Ratiometric imaging Fluorescence

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青光眼局部用药的依从性及其障碍

国际眼科杂志 2024年第6期24卷 835-841页

作者： Albert Saladrigas valeria Opazo Elena Milla 圣十字圣保罗医院眼科西班牙巴塞罗那08041 西班牙巴塞罗那临床医院临床眼科研究所 08036

目的:评估接受局部眼内压(IOP)降低治疗患者的药物依从性,并确定接受青光眼专家治疗的患者与接受普通眼科医生随访患者之间的药物依从性是否存在差异及导致依从性差的多个障碍。方法:横断面调查研究。纳入2020-10/2021-02共54名患者行... 详细信息

目的:评估接受局部眼内压(IOP)降低治疗患者的药物依从性,并确定接受青光眼专家治疗的患者与接受普通眼科医生随访患者之间的药物依从性是否存在差异及导致依从性差的多个障碍。方法:横断面调查研究。纳入2020-10/2021-02共54名患者行局部降眼压药物,且受试者完成了一份定制调查问卷,评估药物依从性及其障碍。结果:约60%受试者未完全依从局部治疗。Pearson检验表明,依从性与是否接受青光眼专家的随访之间无显著关联(χ^(2)=1.2468,P=0.5361)。其次,43%的受试者排斥滴眼液,Logistic回归分析显示,受试者表现出低依从性(β_(1)=3.168,P=0.0367)。结论:问卷可有效评估对局部降IOP治疗的药物依从性及其障碍。本研究药物依从率非常低,因此必须实施策略应对影响依从性最常见的障碍。

关键词：药物依从性局部治疗滴眼液障碍青光眼