Pub Date : 2024-10-16DOI: 10.3390/biomedicines12102357
Andrea Šupe Parun, Boris Brkljačić, Gordana Ivanac, Vanja Tešić
Objective: To evaluate the diagnostic performance of abbreviated breast MRI compared with mammography in women with a family history of breast cancer included in the Croatian National Breast Screening Program.
Methods: 178 women with a family history of breast cancer aged 50 to 69 underwent abbreviated breast MRI and mammography. Radiological findings for each method were categorized according to the BI-RADS classification. The gold standard for assessing the diagnostic accuracy of breast MRI and mammography, in terms of suspicious BI-RADS 4 and BI-RADS 5 findings, was the histopathological diagnosis. Performance measures, including cancer detection rates, specificity, sensitivity, and positive and negative predictive values, were calculated for both imaging methods.
Results: Twelve new cases of breast cancer were detected, with seven (58.3%) identified only by abbreviated breast MRI, four (33.3%) detected by both mammography and breast MRI, and one (8.3%) diagnosed only by mammography. Diagnostic accuracy parameters for abbreviated breast MRI were 91.67% sensitivity, 94.58% specificity, 55.0% positive predictive value (PPV), and 99.37% negative predictive value (NPV), while for mammography, the corresponding values were 41.67%, 96.39%, 45.46%, and 95.81%, respectively.
Conclusions: Abbreviated breast MRI is a useful supplement to screening mammography in women with a family history of breast cancer. Considering the results of the conducted research, it is recommended to assess whether women with a family history of breast cancer have an increased risk and subsequently provide annual abbreviated breast MRI in addition to mammography for early detection of breast cancer.
目的方法:178 名 50 至 69 岁有乳腺癌家族史的妇女接受了简略乳腺 MRI 和乳腺 X 光检查。根据 BI-RADS 分类法对每种方法的放射学结果进行分类。就可疑的 BI-RADS 4 和 BI-RADS 5 结果而言,评估乳腺 MRI 和乳腺 X 光造影诊断准确性的金标准是组织病理学诊断。计算了两种成像方法的性能指标,包括癌症检出率、特异性、灵敏度以及阳性和阴性预测值:结果:共发现 12 例新的乳腺癌病例,其中 7 例(58.3%)仅通过简略乳腺 MRI 发现,4 例(33.3%)通过乳腺 X 光检查和乳腺 MRI 发现,1 例(8.3%)仅通过乳腺 X 光检查确诊。简略乳腺磁共振成像的诊断准确性参数分别为敏感性91.67%、特异性94.58%、阳性预测值(PPV)55.0%和阴性预测值(NPV)99.37%,而乳腺X光检查的相应数值分别为41.67%、96.39%、45.46%和95.81%:对于有乳腺癌家族史的妇女来说,简略乳腺磁共振成像是乳腺放射摄影筛查的有效补充。考虑到研究结果,建议对有乳腺癌家族史的妇女进行评估,以确定其患乳腺癌的风险是否会增加,然后每年在乳房 X 光检查的基础上进行简略乳房 MRI 检查,以早期发现乳腺癌。
{"title":"Abbreviated Breast MRI as a Supplement to Mammography in Family Risk History of Breast Cancer within the Croatian National Breast Screening Program.","authors":"Andrea Šupe Parun, Boris Brkljačić, Gordana Ivanac, Vanja Tešić","doi":"10.3390/biomedicines12102357","DOIUrl":"10.3390/biomedicines12102357","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the diagnostic performance of abbreviated breast MRI compared with mammography in women with a family history of breast cancer included in the Croatian National Breast Screening Program.</p><p><strong>Methods: </strong>178 women with a family history of breast cancer aged 50 to 69 underwent abbreviated breast MRI and mammography. Radiological findings for each method were categorized according to the BI-RADS classification. The gold standard for assessing the diagnostic accuracy of breast MRI and mammography, in terms of suspicious BI-RADS 4 and BI-RADS 5 findings, was the histopathological diagnosis. Performance measures, including cancer detection rates, specificity, sensitivity, and positive and negative predictive values, were calculated for both imaging methods.</p><p><strong>Results: </strong>Twelve new cases of breast cancer were detected, with seven (58.3%) identified only by abbreviated breast MRI, four (33.3%) detected by both mammography and breast MRI, and one (8.3%) diagnosed only by mammography. Diagnostic accuracy parameters for abbreviated breast MRI were 91.67% sensitivity, 94.58% specificity, 55.0% positive predictive value (PPV), and 99.37% negative predictive value (NPV), while for mammography, the corresponding values were 41.67%, 96.39%, 45.46%, and 95.81%, respectively.</p><p><strong>Conclusions: </strong>Abbreviated breast MRI is a useful supplement to screening mammography in women with a family history of breast cancer. Considering the results of the conducted research, it is recommended to assess whether women with a family history of breast cancer have an increased risk and subsequently provide annual abbreviated breast MRI in addition to mammography for early detection of breast cancer.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.3390/biomedicines12102369
Nele Rolfs, Cynthia Huber, Bernd Opgen-Rhein, Isabell Altmann, Felix Anderheiden, Tobias Hecht, Marcus Fischer, Gesa Wiegand, Katja Reineker, Inga Voges, Daniela Kiski, Wiebke Frede, Martin Boehne, Malika Khedim, Daniel Messroghli, Karin Klingel, Eicke Schwarzkopf, Thomas Pickardt, Stephan Schubert, Fatima I Lunze, Franziska Seidel
Background/Objectives: Risk assessment in pediatric myocarditis is challenging, particularly when left ventricular ejection fraction (LVEF) is preserved. This study aimed to evaluate LV myocardial deformation using speckle-tracking echocardiography (STE)-derived longitudinal +strain (LS) and assessed its diagnostic and prognostic value in children with myocarditis. Methods: Retrospective STE-derived layer-specific LV LS analysis was performed on echocardiograms from patients within the multicenter, prospective registry for pediatric myocarditis "MYKKE". Age- and sex-adjusted logistic regression and ROC analysis identified predictors of cardiac arrhythmias (ventricular tachycardia, ventricular fibrillation, atrioventricular blockage III°) and major adverse cardiac events (MACE: need for mechanical circulatory support (MCS), cardiac transplantation, and/or cardiac death). Results: Echocardiograms from 175 patients (median age 15 years, IQR 7.9-16.5 years; 70% male) across 13 centers were included. Cardiac arrhythmias occurred in 36 patients (21%), and MACE in 28 patients (16%). Impaired LV LS strongly correlated with reduced LVEF (r > 0.8). Impaired layer-specific LV LS, reduced LVEF, LV dilatation, and increased BSA-indexed LV mass, were associated with the occurrence of MACE and cardiac arrhythmias. In patients with preserved LVEF, LV LS alone predicted cardiac arrhythmias (p < 0.001), with optimal cutoff values of -18.0% for endocardial LV LS (sensitivity 0.69, specificity 0.94) and -17.0% for midmyocardial LV LS (sensitivity 0.81, specificity 0.75). Conclusions: In pediatric myocarditis, STE-derived LV LS is not only a valuable tool for assessing systolic myocardial dysfunction and predicting MACE but also identifies patients at risk for cardiac arrhythmias, even in the context of preserved LVEF.
{"title":"Prognostic Value of Speckle Tracking Echocardiography-Derived Strain in Unmasking Risk for Arrhythmias in Children with Myocarditis.","authors":"Nele Rolfs, Cynthia Huber, Bernd Opgen-Rhein, Isabell Altmann, Felix Anderheiden, Tobias Hecht, Marcus Fischer, Gesa Wiegand, Katja Reineker, Inga Voges, Daniela Kiski, Wiebke Frede, Martin Boehne, Malika Khedim, Daniel Messroghli, Karin Klingel, Eicke Schwarzkopf, Thomas Pickardt, Stephan Schubert, Fatima I Lunze, Franziska Seidel","doi":"10.3390/biomedicines12102369","DOIUrl":"10.3390/biomedicines12102369","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Risk assessment in pediatric myocarditis is challenging, particularly when left ventricular ejection fraction (LVEF) is preserved. This study aimed to evaluate LV myocardial deformation using speckle-tracking echocardiography (STE)-derived longitudinal +strain (LS) and assessed its diagnostic and prognostic value in children with myocarditis. <b>Methods:</b> Retrospective STE-derived layer-specific LV LS analysis was performed on echocardiograms from patients within the multicenter, prospective registry for pediatric myocarditis \"MYKKE\". Age- and sex-adjusted logistic regression and ROC analysis identified predictors of cardiac arrhythmias (ventricular tachycardia, ventricular fibrillation, atrioventricular blockage III°) and major adverse cardiac events (MACE: need for mechanical circulatory support (MCS), cardiac transplantation, and/or cardiac death). <b>Results:</b> Echocardiograms from 175 patients (median age 15 years, IQR 7.9-16.5 years; 70% male) across 13 centers were included. Cardiac arrhythmias occurred in 36 patients (21%), and MACE in 28 patients (16%). Impaired LV LS strongly correlated with reduced LVEF (r > 0.8). Impaired layer-specific LV LS, reduced LVEF, LV dilatation, and increased BSA-indexed LV mass, were associated with the occurrence of MACE and cardiac arrhythmias. In patients with preserved LVEF, LV LS alone predicted cardiac arrhythmias (<i>p</i> < 0.001), with optimal cutoff values of -18.0% for endocardial LV LS (sensitivity 0.69, specificity 0.94) and -17.0% for midmyocardial LV LS (sensitivity 0.81, specificity 0.75). <b>Conclusions:</b> In pediatric myocarditis, STE-derived LV LS is not only a valuable tool for assessing systolic myocardial dysfunction and predicting MACE but also identifies patients at risk for cardiac arrhythmias, even in the context of preserved LVEF.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.3390/biomedicines12102362
Michael S McGrath, Rongzhen Zhang, Paige M Bracci, Ari Azhir, Bruce D Forrest
Background/objective: Amyotrophic lateral sclerosis (ALS) is a diagnosis that incorporates a heterogeneous set of neurodegenerative processes into a single progressive and uniformly fatal disease making the development of a uniformly applicable therapeutic difficult. Recent multinational ALS natural history incidence studies have identified systemic chronic activation of the innate immune system as a major risk factor for developing ALS. Persistent immune activation in patients with ALS leads to loss of muscle and lowering of serum creatinine. The goal of the current study was to test whether the slowing of nerve and muscle destruction in NP001-treated ALS patients compared with controls in phase 2 studies would lead to extension of survival.
Methods: Phase 2 clinical studies with NP001, an intravenously administered form of the innate immune system regulator NaClO2, are now reporting long-term survival benefits for drug recipients vs. placebo controls after only six months of intermittent treatment. As a prodrug, NP001 is converted by macrophages to taurine chloramine, a long-lived regulator of inflammation. We performed a pooled analysis of all patients who had completed the studies in two six-month NP001 phase 2 trials. Changes in respiratory vital capacity and the muscle mass product, creatinine, defined treated patients who, compared to placebo, had up to a year of extended survival.
Conclusions: The observed longer survival in ALS patients with the greatest inflammation-associated muscle loss provides further evidence that ALS is a disease of ongoing innate immune dysfunction and that NP001 is a disease-modifying drug with sustained clinical activity.
背景/目的:肌萎缩性脊髓侧索硬化症(ALS)是一种将多种神经退行性病变过程整合为单一的渐进性和致命性疾病的诊断方法,因此很难开发出统一适用的疗法。最近的多国 ALS 自然史发病率研究发现,先天性免疫系统的系统性慢性激活是 ALS 发病的主要风险因素。ALS 患者体内持续的免疫激活会导致肌肉萎缩和血清肌酐降低。本研究的目的是测试在二期研究中,与对照组相比,NP001治疗ALS患者的神经和肌肉破坏速度减慢是否会导致生存期延长:NP001是一种先天性免疫系统调节剂NaClO2的静脉给药形式,目前进行的2期临床研究报告显示,与安慰剂对照组相比,接受药物治疗的患者仅在6个月的间歇治疗后就获得了长期生存的益处。作为一种原药,NP001 会被巨噬细胞转化为牛磺酸氯胺,这是一种长效的炎症调节剂。我们对两项为期 6 个月的 NP001 2 期试验中完成研究的所有患者进行了汇总分析。与安慰剂相比,接受治疗的患者生存期最长可延长一年:在炎症相关肌肉损失最大的 ALS 患者中观察到的更长生存期进一步证明了 ALS 是一种持续存在先天性免疫功能障碍的疾病,而 NP001 是一种具有持续临床活性的疾病调节药物。
{"title":"Systemic Innate Immune System Restoration as a Therapeutic Approach for Neurodegenerative Disease: Effects of NP001 on Amyotrophic Lateral Sclerosis (ALS) Progression.","authors":"Michael S McGrath, Rongzhen Zhang, Paige M Bracci, Ari Azhir, Bruce D Forrest","doi":"10.3390/biomedicines12102362","DOIUrl":"10.3390/biomedicines12102362","url":null,"abstract":"<p><strong>Background/objective: </strong>Amyotrophic lateral sclerosis (ALS) is a diagnosis that incorporates a heterogeneous set of neurodegenerative processes into a single progressive and uniformly fatal disease making the development of a uniformly applicable therapeutic difficult. Recent multinational ALS natural history incidence studies have identified systemic chronic activation of the innate immune system as a major risk factor for developing ALS. Persistent immune activation in patients with ALS leads to loss of muscle and lowering of serum creatinine. The goal of the current study was to test whether the slowing of nerve and muscle destruction in NP001-treated ALS patients compared with controls in phase 2 studies would lead to extension of survival.</p><p><strong>Methods: </strong>Phase 2 clinical studies with NP001, an intravenously administered form of the innate immune system regulator NaClO<sub>2</sub>, are now reporting long-term survival benefits for drug recipients vs. placebo controls after only six months of intermittent treatment. As a prodrug, NP001 is converted by macrophages to taurine chloramine, a long-lived regulator of inflammation. We performed a pooled analysis of all patients who had completed the studies in two six-month NP001 phase 2 trials. Changes in respiratory vital capacity and the muscle mass product, creatinine, defined treated patients who, compared to placebo, had up to a year of extended survival.</p><p><strong>Conclusions: </strong>The observed longer survival in ALS patients with the greatest inflammation-associated muscle loss provides further evidence that ALS is a disease of ongoing innate immune dysfunction and that NP001 is a disease-modifying drug with sustained clinical activity.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.3390/biomedicines12102367
Bruce D Forrest, Namita A Goyal, Thomas R Fleming, Paige M Bracci, Neil R Brett, Zaeem Khan, Michelle Robinson, Ari Azhir, Michael McGrath
Background/objectives: The aim of this study was to estimate the effect of a 6 months' treatment course of the innate immune modulator NP001 (a pH-adjusted intravenous formulation of purified sodium chlorite), on disease progression, as measured by overall survival (OS) in patients with amyotrophic lateral sclerosis.
Methods: Blinded survival data were retrospectively collected for 268 of the 273 patients who had participated in two phase 2 placebo-controlled clinical trials of NP001 (ClinicalTrials.gov: NCT01281631 and NCT02794857) and received at least one dose of either 1 mg/kg or 2 mg/kg of NP001 as chlorite based on actual body weight, or placebo. Kaplan-Meier methods were used on the intent-to-treat population to estimate survival probabilities.
Results: In the overall population, the median OS was 4.8 months (2.7 years [95% CI: 2.3, 3.5] in the 2 mg/kg NP001group and 2.3 years [95% CI: 1.8, 2.9] in the placebo group). Hazard ratio (HR): 0.77 (95% CI: 0.57, 1.03), p = 0.073. Among patients aged ≤ 65 years, the median OS for the 2 mg/kg NP001 group was 10.8 months (3.3 years [95% CI: 2.4, 3.8] in the 2 mg/kg NP001 group and 2.4 years [95% CI: 1.7, 3.3] in the placebo group). HR: 0.69 (95% CI: 0.50, 0.95). No differences were observed in the 1 mg/kg NP001 group or in patients aged > 65 years.
Conclusions: The findings from this study suggest that a 6 months' treatment course of NP001 resulted in a 4.8-month increase in overall survival in patients with ALS. The findings from this study indicate that targeting inflammation associated with the innate immune system may provide a pathway for new therapeutic options for the treatment of ALS.
{"title":"The Effectiveness of NP001 on the Long-Term Survival of Patients with Amyotrophic Lateral Sclerosis.","authors":"Bruce D Forrest, Namita A Goyal, Thomas R Fleming, Paige M Bracci, Neil R Brett, Zaeem Khan, Michelle Robinson, Ari Azhir, Michael McGrath","doi":"10.3390/biomedicines12102367","DOIUrl":"10.3390/biomedicines12102367","url":null,"abstract":"<p><strong>Background/objectives: </strong>The aim of this study was to estimate the effect of a 6 months' treatment course of the innate immune modulator NP001 (a pH-adjusted intravenous formulation of purified sodium chlorite), on disease progression, as measured by overall survival (OS) in patients with amyotrophic lateral sclerosis.</p><p><strong>Methods: </strong>Blinded survival data were retrospectively collected for 268 of the 273 patients who had participated in two phase 2 placebo-controlled clinical trials of NP001 (ClinicalTrials.gov: NCT01281631 and NCT02794857) and received at least one dose of either 1 mg/kg or 2 mg/kg of NP001 as chlorite based on actual body weight, or placebo. Kaplan-Meier methods were used on the intent-to-treat population to estimate survival probabilities.</p><p><strong>Results: </strong>In the overall population, the median OS was 4.8 months (2.7 years [95% CI: 2.3, 3.5] in the 2 mg/kg NP001group and 2.3 years [95% CI: 1.8, 2.9] in the placebo group). Hazard ratio (HR): 0.77 (95% CI: 0.57, 1.03), <i>p</i> = 0.073. Among patients aged ≤ 65 years, the median OS for the 2 mg/kg NP001 group was 10.8 months (3.3 years [95% CI: 2.4, 3.8] in the 2 mg/kg NP001 group and 2.4 years [95% CI: 1.7, 3.3] in the placebo group). HR: 0.69 (95% CI: 0.50, 0.95). No differences were observed in the 1 mg/kg NP001 group or in patients aged > 65 years.</p><p><strong>Conclusions: </strong>The findings from this study suggest that a 6 months' treatment course of NP001 resulted in a 4.8-month increase in overall survival in patients with ALS. The findings from this study indicate that targeting inflammation associated with the innate immune system may provide a pathway for new therapeutic options for the treatment of ALS.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.3390/biomedicines12102359
Valentina Magri, Luca Marino, Francesco Del Giudice, Michela De Meo, Marco Siringo, Ettore De Berardinis, Orietta Gandini, Daniele Santini, Chiara Nicolazzo, Paola Gazzaniga
Non-muscle-invasive bladder cancer (NMIBC) prognosis varies significantly due to the biological and clinical heterogeneity. High-risk stage T1-G3, comprising 15-20% of NMIBCs, involves the lamina propria and is associated with higher rates of recurrence, progression, and cancer-specific mortality. In the present study, we have evaluated the enumeration of tumour-derived extracellular vesicles (tdEVs) and circulating tumour cells (CTCs) in high-risk NMIBC patients and their correlation with survival outcomes such as time to progression (TTP), and cancer-specific survival (CSS). Eighty-three high-risk T1-G3 NMIBC patients treated between September 2010 and January 2013 were included. Blood samples were collected before a transurethral resection of the bladder (TURB) and analysed using the CellSearch® system. The presence of at least one CTC was associated with a shorter TTP and CSS. Extending follow-up to 120 months and incorporating automated tdEV evaluation using ACCEPT software demonstrated that tdEV count may additionally stratify patient risk. Combining tdEVs and CTCs improves risk stratification for NMIBC progression, suggesting that tdEVs could be valuable biomarkers for prognosis and disease monitoring. Further research is needed to confirm these findings and establish the clinical significance of tdEVs in early-stage cancers.
{"title":"Blood Extracellular Vesicles Beyond Circulating Tumour Cells: A Valuable Risk Stratification Biomarker in High-Risk Non-Muscle-Invasive Bladder Cancer Patients.","authors":"Valentina Magri, Luca Marino, Francesco Del Giudice, Michela De Meo, Marco Siringo, Ettore De Berardinis, Orietta Gandini, Daniele Santini, Chiara Nicolazzo, Paola Gazzaniga","doi":"10.3390/biomedicines12102359","DOIUrl":"10.3390/biomedicines12102359","url":null,"abstract":"<p><p>Non-muscle-invasive bladder cancer (NMIBC) prognosis varies significantly due to the biological and clinical heterogeneity. High-risk stage T1-G3, comprising 15-20% of NMIBCs, involves the lamina propria and is associated with higher rates of recurrence, progression, and cancer-specific mortality. In the present study, we have evaluated the enumeration of tumour-derived extracellular vesicles (tdEVs) and circulating tumour cells (CTCs) in high-risk NMIBC patients and their correlation with survival outcomes such as time to progression (TTP), and cancer-specific survival (CSS). Eighty-three high-risk T1-G3 NMIBC patients treated between September 2010 and January 2013 were included. Blood samples were collected before a transurethral resection of the bladder (TURB) and analysed using the CellSearch<sup>®</sup> system. The presence of at least one CTC was associated with a shorter TTP and CSS. Extending follow-up to 120 months and incorporating automated tdEV evaluation using ACCEPT software demonstrated that tdEV count may additionally stratify patient risk. Combining tdEVs and CTCs improves risk stratification for NMIBC progression, suggesting that tdEVs could be valuable biomarkers for prognosis and disease monitoring. Further research is needed to confirm these findings and establish the clinical significance of tdEVs in early-stage cancers.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.3390/biomedicines12102361
Aizhan Rakhmetullina, Piotr Zielenkiewicz, Norbert Odolczyk
Protein-protein interactions (PPIs) are fundamental to many critical biological processes and are crucial in mediating essential cellular functions across diverse organisms, including bacteria, parasites, and viruses. A notable example is the interaction between the SARS-CoV-2 spike (S) protein and the human angiotensin-converting enzyme 2 (hACE2), which initiates a series of events leading to viral replication. Interrupting this interaction offers a promising strategy for blocking or significantly reducing infection, highlighting its potential as a target for anti-SARS-CoV-2 therapies. This review focuses on the hACE2 and SARS-CoV-2 spike protein interaction, exemplifying the latest advancements in peptide-based strategies for developing PPI inhibitors. We discuss various approaches for creating peptide-based inhibitors that target this critical interaction, aiming to provide potential treatments for COVID-19.
{"title":"Peptide-Based Inhibitors of Protein-Protein Interactions (PPIs): A Case Study on the Interaction Between SARS-CoV-2 Spike Protein and Human Angiotensin-Converting Enzyme 2 (hACE2).","authors":"Aizhan Rakhmetullina, Piotr Zielenkiewicz, Norbert Odolczyk","doi":"10.3390/biomedicines12102361","DOIUrl":"10.3390/biomedicines12102361","url":null,"abstract":"<p><p>Protein-protein interactions (PPIs) are fundamental to many critical biological processes and are crucial in mediating essential cellular functions across diverse organisms, including bacteria, parasites, and viruses. A notable example is the interaction between the SARS-CoV-2 spike (S) protein and the human angiotensin-converting enzyme 2 (hACE2), which initiates a series of events leading to viral replication. Interrupting this interaction offers a promising strategy for blocking or significantly reducing infection, highlighting its potential as a target for anti-SARS-CoV-2 therapies. This review focuses on the hACE2 and SARS-CoV-2 spike protein interaction, exemplifying the latest advancements in peptide-based strategies for developing PPI inhibitors. We discuss various approaches for creating peptide-based inhibitors that target this critical interaction, aiming to provide potential treatments for COVID-19.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.3390/biomedicines12102353
Richard Kraus, Elena Maier, Michael Gruber, Sigrid Wittmann
Background: There is increasing evidence that nitric oxide (nitrogen monoxide, NO) significantly influences immune cellular responses, including those from polymorphonuclear leukocytes (PMNs).
Objective: The aim of this study was to examine a possible effect of NO on PMNs' function (chemotaxis, production of reactive oxygen species (ROS), and NETosis) using live cell imaging. Moreover, we investigated PMN surface epitope and neutrophil oxidative burst under the influence of NO by flow cytometric analysis.
Methods: Whole blood samples were obtained from healthy volunteers, and PMNs were isolated by density centrifugation. Live cell imaging using type I collagen matrix in µSlide IBIDI chemotaxis chambers was conducted in order to observe N-formyl-L-methionyl-L-leucyl-phenylalanine (fMLP)-stimulated PMN chemotaxis, ROS production, and NETosis. In the test group, NO was continuously redirected into the climate chamber of the microscope, so the chemotaxis chambers were surrounded by NO. The same experimental setup without NO served as a control. In addition, isolated PMNs were incubated with nitrogen monoxide (NO) or without (the control). Subsequently, flow cytometry was used to analyze neutrophil antigen expression and oxidative burst.
Results: Our live cell imaging results demonstrated a migration-promoting effect of NO on PMNs. We observed that in the case of prior stimulation by fMLP, NO has no effect on the time course of neutrophil ROS production and NET release. However, flow cytometric analyses demonstrated an increase in ROS production after pretreatment with NO. No NO-dependent differences for the expression of CD11b, CD62L, or CD66b could be observed.
Conclusions: We were able to demonstrate a distinct effect of NO on PMNs' function. The complex interaction between NO and PMNs remains a major research focus, as the exact mechanisms and additional influencing factors remain elusive. Future studies should explore how varying NO concentrations and the timing of NO exposure relative to PMN activation affect its influence.
背景:越来越多的证据表明,一氧化氮(NO越来越多的证据表明,一氧化氮(NO)能显著影响免疫细胞反应,包括多形核白细胞(PMNs)的反应:本研究旨在利用活细胞成像技术研究一氧化氮对 PMNs 功能(趋化、活性氧(ROS)的产生和 NETosis)可能产生的影响。此外,我们还通过流式细胞分析法研究了 NO 影响下的 PMN 表面表位和中性粒细胞氧化爆发:方法:采集健康志愿者的全血样本,通过密度离心分离 PMN。在μSlide IBIDI趋化室中使用I型胶原基质进行活细胞成像,以观察N-甲酰基-L-蛋氨酰-L-亮氨酰-苯丙氨酸(fMLP)刺激的PMN趋化、ROS产生和NETosis。在试验组中,NO 被持续重新导入显微镜的气候室,因此趋化室被 NO 所包围。没有 NO 的相同实验装置作为对照组。此外,分离出的 PMN 与一氧化氮(NO)或不与一氧化氮(NO)孵育(对照组)。随后,使用流式细胞术分析中性粒细胞抗原表达和氧化爆发:结果:我们的活细胞成像结果表明了一氧化氮对 PMN 的迁移促进作用。我们观察到,在事先受到 fMLP 刺激的情况下,NO 对中性粒细胞 ROS 生成和 NET 释放的时间过程没有影响。然而,流式细胞分析表明,在使用 NO 进行预处理后,ROS 的产生有所增加。在 CD11b、CD62L 或 CD66b 的表达方面,没有观察到 NO 依赖性差异:结论:我们能够证明 NO 对 PMN 功能的独特影响。NO与PMN之间复杂的相互作用仍然是研究的重点,因为确切的机制和其他影响因素仍然难以捉摸。未来的研究应探讨不同浓度的 NO 和相对于 PMN 激活的 NO 暴露时间如何影响其影响。
{"title":"Impact of Nitric Oxide on Polymorphonuclear Neutrophils' Function.","authors":"Richard Kraus, Elena Maier, Michael Gruber, Sigrid Wittmann","doi":"10.3390/biomedicines12102353","DOIUrl":"10.3390/biomedicines12102353","url":null,"abstract":"<p><strong>Background: </strong>There is increasing evidence that nitric oxide (nitrogen monoxide, NO) significantly influences immune cellular responses, including those from polymorphonuclear leukocytes (PMNs).</p><p><strong>Objective: </strong>The aim of this study was to examine a possible effect of NO on PMNs' function (chemotaxis, production of reactive oxygen species (ROS), and NETosis) using live cell imaging. Moreover, we investigated PMN surface epitope and neutrophil oxidative burst under the influence of NO by flow cytometric analysis.</p><p><strong>Methods: </strong>Whole blood samples were obtained from healthy volunteers, and PMNs were isolated by density centrifugation. Live cell imaging using type I collagen matrix in µSlide IBIDI chemotaxis chambers was conducted in order to observe N-formyl-L-methionyl-L-leucyl-phenylalanine (fMLP)-stimulated PMN chemotaxis, ROS production, and NETosis. In the test group, NO was continuously redirected into the climate chamber of the microscope, so the chemotaxis chambers were surrounded by NO. The same experimental setup without NO served as a control. In addition, isolated PMNs were incubated with nitrogen monoxide (NO) or without (the control). Subsequently, flow cytometry was used to analyze neutrophil antigen expression and oxidative burst.</p><p><strong>Results: </strong>Our live cell imaging results demonstrated a migration-promoting effect of NO on PMNs. We observed that in the case of prior stimulation by fMLP, NO has no effect on the time course of neutrophil ROS production and NET release. However, flow cytometric analyses demonstrated an increase in ROS production after pretreatment with NO. No NO-dependent differences for the expression of CD11b, CD62L, or CD66b could be observed.</p><p><strong>Conclusions: </strong>We were able to demonstrate a distinct effect of NO on PMNs' function. The complex interaction between NO and PMNs remains a major research focus, as the exact mechanisms and additional influencing factors remain elusive. Future studies should explore how varying NO concentrations and the timing of NO exposure relative to PMN activation affect its influence.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.3390/biomedicines12102354
Briana Maktabi, Abigail Collins, Raihaanah Safee, Jada Bouyer, Alexander S Wisner, Frederick E Williams, Isaac T Schiefer
Background: Zebrafish have become a key model organism in neuroscience research because of their unique advantages. Their genetic, anatomical, and physiological similarities to humans, coupled with their rapid development and transparent embryos, make them an excellent tool for investigating various aspects of neurobiology. They have specifically emerged as a valuable and versatile model organism in biomedical research, including the study of neurological disorders such as multiple sclerosis. Multiple sclerosis is a chronic autoimmune disease known to cause damage to the myelin sheath that protects the nerves in the brain and spinal cord. Objective: This review emphasizes the importance of continued research in both in vitro and in vivo models to advance our understanding of MS and develop effective treatments, ultimately improving the quality of life for those affected by this debilitating disease. Conclusions: Recent studies show the significance of zebrafish as a model organism for investigating demyelination and remyelination processes, providing new insights into MS pathology and potential therapies.
{"title":"Zebrafish as a Model for Multiple Sclerosis.","authors":"Briana Maktabi, Abigail Collins, Raihaanah Safee, Jada Bouyer, Alexander S Wisner, Frederick E Williams, Isaac T Schiefer","doi":"10.3390/biomedicines12102354","DOIUrl":"10.3390/biomedicines12102354","url":null,"abstract":"<p><p><b>Background:</b> Zebrafish have become a key model organism in neuroscience research because of their unique advantages. Their genetic, anatomical, and physiological similarities to humans, coupled with their rapid development and transparent embryos, make them an excellent tool for investigating various aspects of neurobiology. They have specifically emerged as a valuable and versatile model organism in biomedical research, including the study of neurological disorders such as multiple sclerosis. Multiple sclerosis is a chronic autoimmune disease known to cause damage to the myelin sheath that protects the nerves in the brain and spinal cord. <b>Objective:</b> This review emphasizes the importance of continued research in both in vitro and in vivo models to advance our understanding of MS and develop effective treatments, ultimately improving the quality of life for those affected by this debilitating disease. <b>Conclusions:</b> Recent studies show the significance of zebrafish as a model organism for investigating demyelination and remyelination processes, providing new insights into MS pathology and potential therapies.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.3390/biomedicines12102365
Trung T Ngo, Wendy N Barsdell, Phillip C F Law, Carolyn A Arnold, Michael J Chou, Andrew K Nunn, Douglas J Brown, Paul B Fitzgerald, Stephen J Gibson, Steven M Miller
Background: Caloric vestibular stimulation (CVS) is a well-established neurological diagnostic technique that also induces many phenomenological modulations, including reductions in phantom limb pain (PLP), spinal cord injury pain (SCIP), and central post-stroke pain.
Objective: We aimed to assess in a variety of persistent pain (PP) conditions (i) short-term pain modulation by CVS relative to a forehead ice pack cold-arousal control procedure and (ii) the duration and repeatability of CVS modulations. The tolerability of CVS was also assessed and has been reported separately.
Methods: We conducted a convenience-based non-randomised single-blinded placebo-controlled study. Thirty-eight PP patients were assessed (PLP, n = 8; SCIP, n = 12; complex regional pain syndrome, CRPS, n = 14; non-specific PP, n = 4). Patients underwent 1-3 separate-day sessions of iced-water right-ear CVS. All but four also underwent the ice pack procedure. Analyses used patient-reported numerical rating scale pain intensity (NRS-PI) scores for pain and allodynia.
Results: Across all groups, NRS-PI for pain was significantly lower within 30 min post-CVS than post-ice pack (p < 0.01). Average reductions were 24.8% (CVS) and 6.4% (ice pack). CRPS appeared most responsive to CVS, while PLP and SCIP responses were less than expected from previous reports. The strongest CVS pain reductions lasted hours to over three weeks. CVS also induced substantial reductions in allodynia in three of nine allodynic CRPS patients, lasting 24 h to 1 month. As reported elsewhere, only one patient experienced emesis and CVS was widely rated by patients as a tolerable PP management intervention.
Conclusions: Although these results require interpretative caution, CVS was found to modulate pain relative to an ice pack control. CVS also modulated allodynia in some cases. CVS should be examined for pain management efficacy using randomised controlled trials.
{"title":"Bedside Neuromodulation of Persistent Pain and Allodynia with Caloric Vestibular Stimulation.","authors":"Trung T Ngo, Wendy N Barsdell, Phillip C F Law, Carolyn A Arnold, Michael J Chou, Andrew K Nunn, Douglas J Brown, Paul B Fitzgerald, Stephen J Gibson, Steven M Miller","doi":"10.3390/biomedicines12102365","DOIUrl":"10.3390/biomedicines12102365","url":null,"abstract":"<p><strong>Background: </strong>Caloric vestibular stimulation (CVS) is a well-established neurological diagnostic technique that also induces many phenomenological modulations, including reductions in phantom limb pain (PLP), spinal cord injury pain (SCIP), and central post-stroke pain.</p><p><strong>Objective: </strong>We aimed to assess in a variety of persistent pain (PP) conditions (i) short-term pain modulation by CVS relative to a forehead ice pack cold-arousal control procedure and (ii) the duration and repeatability of CVS modulations. The tolerability of CVS was also assessed and has been reported separately.</p><p><strong>Methods: </strong>We conducted a convenience-based non-randomised single-blinded placebo-controlled study. Thirty-eight PP patients were assessed (PLP, <i>n</i> = 8; SCIP, <i>n</i> = 12; complex regional pain syndrome, CRPS, <i>n</i> = 14; non-specific PP, <i>n</i> = 4). Patients underwent 1-3 separate-day sessions of iced-water right-ear CVS. All but four also underwent the ice pack procedure. Analyses used patient-reported numerical rating scale pain intensity (NRS-PI) scores for pain and allodynia.</p><p><strong>Results: </strong>Across all groups, NRS-PI for pain was significantly lower within 30 min post-CVS than post-ice pack (<i>p</i> < 0.01). Average reductions were 24.8% (CVS) and 6.4% (ice pack). CRPS appeared most responsive to CVS, while PLP and SCIP responses were less than expected from previous reports. The strongest CVS pain reductions lasted hours to over three weeks. CVS also induced substantial reductions in allodynia in three of nine allodynic CRPS patients, lasting 24 h to 1 month. As reported elsewhere, only one patient experienced emesis and CVS was widely rated by patients as a tolerable PP management intervention.</p><p><strong>Conclusions: </strong>Although these results require interpretative caution, CVS was found to modulate pain relative to an ice pack control. CVS also modulated allodynia in some cases. CVS should be examined for pain management efficacy using randomised controlled trials.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.3390/biomedicines12102363
Daniel Rivera, Tirone Young, Akhil Rao, Jack Y Zhang, Cole Brown, Lily Huo, Tyree Williams, Benjamin Rodriguez, Alexander J Schupper
Background: Neurosurgery demands exceptional precision due to the brain's complex and delicate structures, necessitating precise targeting of pathological targets. Achieving optimal outcomes depends on the surgeon's ability to accurately differentiate between healthy and pathological tissues during operations. Raman spectroscopy (RS) has emerged as a promising innovation, offering real-time, in vivo non-invasive biochemical tissue characterization. This literature review evaluates the current research on RS applications in intraoperative neurosurgery, emphasizing its potential to enhance surgical precision and patient outcomes.
Methods: Following PRISMA guidelines, a comprehensive systematic review was conducted using PubMed to extract relevant peer-reviewed articles. The inclusion criteria focused on original research discussing real-time RS applications with human tissue samples in or near the operating room, excluding retrospective studies, reviews, non-human research, and other non-relevant publications.
Results: Our findings demonstrate that RS significantly improves tumor margin delineation, with handheld devices achieving high sensitivity and specificity. Stimulated Raman Histology (SRH) provides rapid, high-resolution tissue images comparable to traditional histopathology but with reduced time to diagnosis. Additionally, RS shows promise in identifying tumor types and grades, aiding precise surgical decision-making. RS techniques have been particularly beneficial in enhancing the accuracy of glioma surgeries, where distinguishing between tumor and healthy tissue is critical. By providing real-time molecular data, RS aids neurosurgeons in maximizing the extent of resection (EOR) while minimizing damage to normal brain tissue, potentially improving patient outcomes and reducing recurrence rates.
Conclusions: This review underscores the transformative potential of RS in neurosurgery, advocating for continued innovation and research to fully realize its benefits. Despite its substantial potential, further research is needed to validate RS's clinical utility and cost-effectiveness.
{"title":"Current Applications of Raman Spectroscopy in Intraoperative Neurosurgery.","authors":"Daniel Rivera, Tirone Young, Akhil Rao, Jack Y Zhang, Cole Brown, Lily Huo, Tyree Williams, Benjamin Rodriguez, Alexander J Schupper","doi":"10.3390/biomedicines12102363","DOIUrl":"10.3390/biomedicines12102363","url":null,"abstract":"<p><strong>Background: </strong>Neurosurgery demands exceptional precision due to the brain's complex and delicate structures, necessitating precise targeting of pathological targets. Achieving optimal outcomes depends on the surgeon's ability to accurately differentiate between healthy and pathological tissues during operations. Raman spectroscopy (RS) has emerged as a promising innovation, offering real-time, in vivo non-invasive biochemical tissue characterization. This literature review evaluates the current research on RS applications in intraoperative neurosurgery, emphasizing its potential to enhance surgical precision and patient outcomes.</p><p><strong>Methods: </strong>Following PRISMA guidelines, a comprehensive systematic review was conducted using PubMed to extract relevant peer-reviewed articles. The inclusion criteria focused on original research discussing real-time RS applications with human tissue samples in or near the operating room, excluding retrospective studies, reviews, non-human research, and other non-relevant publications.</p><p><strong>Results: </strong>Our findings demonstrate that RS significantly improves tumor margin delineation, with handheld devices achieving high sensitivity and specificity. Stimulated Raman Histology (SRH) provides rapid, high-resolution tissue images comparable to traditional histopathology but with reduced time to diagnosis. Additionally, RS shows promise in identifying tumor types and grades, aiding precise surgical decision-making. RS techniques have been particularly beneficial in enhancing the accuracy of glioma surgeries, where distinguishing between tumor and healthy tissue is critical. By providing real-time molecular data, RS aids neurosurgeons in maximizing the extent of resection (EOR) while minimizing damage to normal brain tissue, potentially improving patient outcomes and reducing recurrence rates.</p><p><strong>Conclusions: </strong>This review underscores the transformative potential of RS in neurosurgery, advocating for continued innovation and research to fully realize its benefits. Despite its substantial potential, further research is needed to validate RS's clinical utility and cost-effectiveness.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"12 10","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}