Pub Date : 2024-05-08DOI: 10.3390/diseases12050096
V. Nagesh, Izage Kianifar Aguilar, Daniel Elias, Charlene Mansour, Hadrian Hoang-Vu Tran, Ruchi Bhuju, Tanni Sethi, P. R. P. Sanjeeva, Marco Gonzalez Rivas, Emelyn Martinez, Auda Auda, Nazir Ahmed, Shawn Philip, Simcha I Weissman, J. Sotiriadis, Ayrton I Bangolo
Background: Appendiceal neuroendocrine tumors (NETs) rank as the third most frequent neoplasm affecting the appendix, originating from enterochromaffin cells. This study aims to evaluate the influence of various prognostic factors on the mortality rates of patients diagnosed with NETs of the appendix. Methods: Conducted retrospectively, the study involved 3346 patients, utilizing data sourced from the Surveillance, Epidemiology, and End Results (SEER) database. Our analysis centered on investigating demographic characteristics, clinical features, overall mortality (OM), and cancer-specific mortality (CSM) among the cohort. Variables showing a p-value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox regression analysis. A Hazard Ratio (HR) > 1 indicated an unfavorable prognosis. Results: In the multivariate analysis, higher OM and CSM were observed in males, older age groups, tumors with distant metastasis, poorly differentiated tumors, and those who underwent chemotherapy. Non-Hispanic Black individuals showed elevated mortality rates. Conclusion: Delayed diagnosis may contribute to the increased mortality in this community. Improved access to healthcare and treatment is crucial for addressing these disparities. Larger prospective studies are needed to pinpoint the underlying causes of elevated mortality in non-Hispanic Black populations, and randomized controlled trials (RCTs) are warranted to evaluate therapies for advanced-stage appendix NETs.
{"title":"Factors Affecting Survival Outcomes in Neuroendocrine Tumor of the Appendix over the Past Two Decades","authors":"V. Nagesh, Izage Kianifar Aguilar, Daniel Elias, Charlene Mansour, Hadrian Hoang-Vu Tran, Ruchi Bhuju, Tanni Sethi, P. R. P. Sanjeeva, Marco Gonzalez Rivas, Emelyn Martinez, Auda Auda, Nazir Ahmed, Shawn Philip, Simcha I Weissman, J. Sotiriadis, Ayrton I Bangolo","doi":"10.3390/diseases12050096","DOIUrl":"https://doi.org/10.3390/diseases12050096","url":null,"abstract":"Background: Appendiceal neuroendocrine tumors (NETs) rank as the third most frequent neoplasm affecting the appendix, originating from enterochromaffin cells. This study aims to evaluate the influence of various prognostic factors on the mortality rates of patients diagnosed with NETs of the appendix. Methods: Conducted retrospectively, the study involved 3346 patients, utilizing data sourced from the Surveillance, Epidemiology, and End Results (SEER) database. Our analysis centered on investigating demographic characteristics, clinical features, overall mortality (OM), and cancer-specific mortality (CSM) among the cohort. Variables showing a p-value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox regression analysis. A Hazard Ratio (HR) > 1 indicated an unfavorable prognosis. Results: In the multivariate analysis, higher OM and CSM were observed in males, older age groups, tumors with distant metastasis, poorly differentiated tumors, and those who underwent chemotherapy. Non-Hispanic Black individuals showed elevated mortality rates. Conclusion: Delayed diagnosis may contribute to the increased mortality in this community. Improved access to healthcare and treatment is crucial for addressing these disparities. Larger prospective studies are needed to pinpoint the underlying causes of elevated mortality in non-Hispanic Black populations, and randomized controlled trials (RCTs) are warranted to evaluate therapies for advanced-stage appendix NETs.","PeriodicalId":11200,"journal":{"name":"Diseases","volume":" 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140997900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-08DOI: 10.3390/diseases12050097
Vanessa A. Araújo, Jefferson S. Souza, Bruna M. Giglio, P. C. Lobo, Gustavo D. Pimentel
Background: COVID-19 is an infectious disease characterized by a severe catabolic and inflammatory state, leading to loss of muscle mass. The assessment of muscle mass can be useful to identify nutritional risk and assist in early management, especially in older adults who have high nutritional risks. The aim of this study was to evaluate the association of calf circumference (CC) with clinical and biochemical markers and mortality in older adults with COVID-19 admitted to the intensive care unit (ICU). Methods: A retrospective cross-sectional study was conducted in a public hospital. CC was adjusted for body mass index (BMI), reducing 3, 7, or 12 cm for a BMI of 25–29.9, 30–39.9, and ≥40 kg/m2, respectively, and classified as reduced when <33 cm for women and <34 cm for men. Pearson’s correlation between BMI and CC was performed to assess the association between variables. Regression analysis was adjusted for sex, age, and BMI variables. Cox regression was used to assess survival related to CC. Results: A total of 208 older adults diagnosed with COVID-19 admitted to ICU were included, of which 84% (n = 176) were classified as having reduced CC. These patients were older, with lower BMI, higher nutritional risk, malnourished, and higher concentration of urea and urea–creatinine ratio (UCR) compared with the group with normal CC. There was an association between edematous patients at nutritional risk and malnourished with reduced CC in the Cox regression, either adjusted or not for confounding. Conclusions: CC was not associated with severity, biochemical markers, or mortality in older adults with COVID-19 admitted to the ICU, but it was associated with moderately malnourished patients assessed by subjective global assessment (SGA).
背景：COVID-19 是一种传染性疾病，其特点是严重的分解代谢和炎症状态，导致肌肉质量下降。肌肉质量评估有助于识别营养风险并协助早期管理，尤其是对营养风险较高的老年人。本研究旨在评估入住重症监护室（ICU）的患有 COVID-19 的老年人的小腿围（CC）与临床和生化指标及死亡率的关系。研究方法在一家公立医院进行了一项回顾性横断面研究。CC根据体重指数（BMI）进行调整，BMI为25-29.9、30-39.9和≥40 kg/m2时，CC分别减少3、7或12厘米，当女性<33厘米和男性<34厘米时，CC被归类为减少。对 BMI 和 CC 之间的皮尔逊相关性进行了分析，以评估变量之间的联系。回归分析对性别、年龄和 BMI 变量进行了调整。Cox 回归用于评估与 CC 相关的存活率。结果：共纳入了 208 名被诊断为 COVID-19 的入住重症监护室的老年人，其中 84% （n = 176）被归类为 CC 下降。与 CC 正常组相比，这些患者年龄更大、体重指数（BMI）更低、营养风险更高、营养不良、尿素浓度和尿素-肌酐比值（UCR）更高。无论是否对混杂因素进行调整，在考克斯回归中，有营养风险和营养不良的水肿患者与 CC 降低之间存在关联。结论：CC在入住重症监护室的患有 COVID-19 的老年人中，CC 与病情严重程度、生化指标或死亡率无关，但与通过主观全面评估（SGA）评定的中度营养不良患者有关。
{"title":"Association of Calf Circumference with Clinical and Biochemical Markers in Older Adults with COVID-19 Admitted at Intensive Care Unit: A Retrospective Cross-Sectional Study","authors":"Vanessa A. Araújo, Jefferson S. Souza, Bruna M. Giglio, P. C. Lobo, Gustavo D. Pimentel","doi":"10.3390/diseases12050097","DOIUrl":"https://doi.org/10.3390/diseases12050097","url":null,"abstract":"Background: COVID-19 is an infectious disease characterized by a severe catabolic and inflammatory state, leading to loss of muscle mass. The assessment of muscle mass can be useful to identify nutritional risk and assist in early management, especially in older adults who have high nutritional risks. The aim of this study was to evaluate the association of calf circumference (CC) with clinical and biochemical markers and mortality in older adults with COVID-19 admitted to the intensive care unit (ICU). Methods: A retrospective cross-sectional study was conducted in a public hospital. CC was adjusted for body mass index (BMI), reducing 3, 7, or 12 cm for a BMI of 25–29.9, 30–39.9, and ≥40 kg/m2, respectively, and classified as reduced when <33 cm for women and <34 cm for men. Pearson’s correlation between BMI and CC was performed to assess the association between variables. Regression analysis was adjusted for sex, age, and BMI variables. Cox regression was used to assess survival related to CC. Results: A total of 208 older adults diagnosed with COVID-19 admitted to ICU were included, of which 84% (n = 176) were classified as having reduced CC. These patients were older, with lower BMI, higher nutritional risk, malnourished, and higher concentration of urea and urea–creatinine ratio (UCR) compared with the group with normal CC. There was an association between edematous patients at nutritional risk and malnourished with reduced CC in the Cox regression, either adjusted or not for confounding. Conclusions: CC was not associated with severity, biochemical markers, or mortality in older adults with COVID-19 admitted to the ICU, but it was associated with moderately malnourished patients assessed by subjective global assessment (SGA).","PeriodicalId":11200,"journal":{"name":"Diseases","volume":"210 s695","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141002043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-06DOI: 10.3390/diseases12050095
V. Calcaterra, Sara Zanelli, A. Foppiani, Elvira Verduci, Beatrice Benatti, Roberto Bollina, Francesco Bombaci, Antonio Brucato, Selene Cammarata, Elisa Calabrò, G. Cirnigliaro, Silvia Della Torre, B. Dell'Osso, C. Moltrasio, A. Marzano, Chiara Nostro, M. Romagnuolo, Lucia Trotta, V. Savasi, Valeria Smiroldo, G. Zuccotti
Long COVID affects both children and adults, including subjects who experienced severe, mild, or even asymptomatic SARS-CoV-2 infection. We have provided a comprehensive overview of the incidence, clinical characteristics, risk factors, and outcomes of persistent COVID-19 symptoms in both children and adults, encompassing vulnerable populations, such as pregnant women and oncological patients. Our objective is to emphasize the critical significance of adopting an integrated approach for the early detection and appropriate management of long COVID. The incidence and severity of long COVID symptoms can have a significant impact on the quality of life of patients and the course of disease in the case of pre-existing pathologies. Particularly, in fragile and vulnerable patients, the presence of PASC is related to significantly worse survival, independent from pre-existing vulnerabilities and treatment. It is important try to achieve an early recognition and management. Various mechanisms are implicated, resulting in a wide range of clinical presentations. Understanding the specific mechanisms and risk factors involved in long COVID is crucial for tailoring effective interventions and support strategies. Management approaches involve comprehensive biopsychosocial assessments and treatment of symptoms and comorbidities, such as autonomic dysfunction, as well as multidisciplinary rehabilitation. The overall course of long COVID is one of gradual improvement, with recovery observed in the majority, though not all, of patients. As the research on long-COVID continues to evolve, ongoing studies are likely to shed more light on the intricate relationship between chronic diseases, such as oncological status, cardiovascular diseases, psychiatric disorders, and the persistent effects of SARS-CoV-2 infection. This information could guide healthcare providers, researchers, and policymakers in developing targeted interventions.
{"title":"Long COVID in Children, Adults, and Vulnerable Populations: A Comprehensive Overview for an Integrated Approach","authors":"V. Calcaterra, Sara Zanelli, A. Foppiani, Elvira Verduci, Beatrice Benatti, Roberto Bollina, Francesco Bombaci, Antonio Brucato, Selene Cammarata, Elisa Calabrò, G. Cirnigliaro, Silvia Della Torre, B. Dell'Osso, C. Moltrasio, A. Marzano, Chiara Nostro, M. Romagnuolo, Lucia Trotta, V. Savasi, Valeria Smiroldo, G. Zuccotti","doi":"10.3390/diseases12050095","DOIUrl":"https://doi.org/10.3390/diseases12050095","url":null,"abstract":"Long COVID affects both children and adults, including subjects who experienced severe, mild, or even asymptomatic SARS-CoV-2 infection. We have provided a comprehensive overview of the incidence, clinical characteristics, risk factors, and outcomes of persistent COVID-19 symptoms in both children and adults, encompassing vulnerable populations, such as pregnant women and oncological patients. Our objective is to emphasize the critical significance of adopting an integrated approach for the early detection and appropriate management of long COVID. The incidence and severity of long COVID symptoms can have a significant impact on the quality of life of patients and the course of disease in the case of pre-existing pathologies. Particularly, in fragile and vulnerable patients, the presence of PASC is related to significantly worse survival, independent from pre-existing vulnerabilities and treatment. It is important try to achieve an early recognition and management. Various mechanisms are implicated, resulting in a wide range of clinical presentations. Understanding the specific mechanisms and risk factors involved in long COVID is crucial for tailoring effective interventions and support strategies. Management approaches involve comprehensive biopsychosocial assessments and treatment of symptoms and comorbidities, such as autonomic dysfunction, as well as multidisciplinary rehabilitation. The overall course of long COVID is one of gradual improvement, with recovery observed in the majority, though not all, of patients. As the research on long-COVID continues to evolve, ongoing studies are likely to shed more light on the intricate relationship between chronic diseases, such as oncological status, cardiovascular diseases, psychiatric disorders, and the persistent effects of SARS-CoV-2 infection. This information could guide healthcare providers, researchers, and policymakers in developing targeted interventions.","PeriodicalId":11200,"journal":{"name":"Diseases","volume":"60 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141007699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-06DOI: 10.3390/diseases12050091
Jakub Bargiel, M. Gontarz, Krzysztof Gąsiorowski, T. Marecik, Paweł Szczurowski, J. Zapała, G. Wyszyńska-Pawelec
(1) Background: Dermoid cysts occurring in the sublingual space are uncommon, typically manifesting as painless, gradually enlarging masses, usually not exceeding 3 cm in diameter. These cysts can resemble various conditions due to their clinical presentation, with a relatively low occurrence rate in the oral cavity, accounting for about 1.6% of all dermoid cysts. (2) Methods: We present the case of a 17-year-old female with a giant dermoid cyst involving the submental, sublingual, and lingual areas, undiagnosed for several years. Diagnosis was achieved through MRI and fine-needle aspiration, leading to the decision for surgical removal through a cervical approach. (3) Results: The healing process was uneventful. From the first day post-surgery, the patient began myofunctional therapy, successfully regaining proper tongue functions. Throughout a 24-month follow-up, the patient remained symptom-free. (4) Conclusions: A cervical approach can successfully treat giant oral dermoid cysts involving submental, sublingual, and lingual spaces. Tongue function can be successfully regained through myofunctional therapy after surgical treatment.
{"title":"Giant Sublingual, Submental, and Lingual Dermoid Cyst Restricting Tongue Movement Undiagnosed for Several Years","authors":"Jakub Bargiel, M. Gontarz, Krzysztof Gąsiorowski, T. Marecik, Paweł Szczurowski, J. Zapała, G. Wyszyńska-Pawelec","doi":"10.3390/diseases12050091","DOIUrl":"https://doi.org/10.3390/diseases12050091","url":null,"abstract":"(1) Background: Dermoid cysts occurring in the sublingual space are uncommon, typically manifesting as painless, gradually enlarging masses, usually not exceeding 3 cm in diameter. These cysts can resemble various conditions due to their clinical presentation, with a relatively low occurrence rate in the oral cavity, accounting for about 1.6% of all dermoid cysts. (2) Methods: We present the case of a 17-year-old female with a giant dermoid cyst involving the submental, sublingual, and lingual areas, undiagnosed for several years. Diagnosis was achieved through MRI and fine-needle aspiration, leading to the decision for surgical removal through a cervical approach. (3) Results: The healing process was uneventful. From the first day post-surgery, the patient began myofunctional therapy, successfully regaining proper tongue functions. Throughout a 24-month follow-up, the patient remained symptom-free. (4) Conclusions: A cervical approach can successfully treat giant oral dermoid cysts involving submental, sublingual, and lingual spaces. Tongue function can be successfully regained through myofunctional therapy after surgical treatment.","PeriodicalId":11200,"journal":{"name":"Diseases","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141008049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-06DOI: 10.3390/diseases12050092
Verena Prokosch, Sarah B. Zwingelberg, Desislava V. Efremova, Francesco Buonfiglio, Norbert Pfeiffer, Adrian Gericke
Purpose: To investigate whether trabecular aspiration (TA) has an effective medium-term intraocular pressure (IOP)-lowering and medication-saving effect in patients with pseudoexfoliation glaucoma (PEG). In addition, a subgroup analysis of patients with or without a previous trabeculectomy was performed. Methods: Records of 290 consecutive eyes with PEG that underwent TA between 2006 and 2012 at the Department of Ophthalmology, Mainz, Germany, were retrospectively analyzed with a follow-up period of 3 years. The main outcomes were IOP and the need for further medical treatment. Results: Of the 290 eyes with PEG that received TA, 167 eyes from 127 patients met the inclusion criteria. Among these eyes, 128 received TA and cataract surgery (Phaco-TA) without having had a trabeculectomy (group I) before, 29 had Phaco-TA after a previous trabeculectomy (group II) and 10 underwent stand-alone TA after a previous trabeculectomy (group III). In the whole cohort, the median IOP decreased immediately after TA and remained significantly lower compared to the baseline throughout the period of 36 months. Likewise, the median number of antiglaucoma drugs was reduced over the whole period. At the same time, in group I, the median IOP and the number of antiglaucoma drugs were reduced over 36 months. In contrast, in the post-trabeculectomy groups (group II and III), the median IOP and the number of antiglaucoma drugs could not be reduced. While most of the patients that received Phaco-TA with or without a previous trabeculectomy (group I and II) did not require further surgical intervention during the follow-up period, almost all patients receiving stand-alone TA after a previous trabeculectomy (group III) needed surgical therapy, most of them between the second and the third year following TA. Conclusions: Phaco-TA has an effective medium-term pressure-lowering and medication-saving effect, especially in patients without a previous trabeculectomy. In trabeculectomized eyes, the effect of TA is limited but still large enough to delay more invasive surgical interventions in some patients.
目的：研究小梁抽吸术（TA）是否能有效降低假性角膜外翻性青光眼（PEG）患者的中期眼压（IOP）并节省用药。此外，还对既往是否进行过小梁切除术的患者进行了分组分析。研究方法回顾性分析了德国美因茨眼科部在 2006 年至 2012 年间连续接受小梁切除术的 290 例 PEG 患者的记录，随访时间为 3 年。主要结果是眼压和是否需要进一步治疗。结果：在接受 TA 治疗的 290 位 PEG 患者中，有 127 位患者的 167 只眼睛符合纳入标准。其中，128只眼睛在接受TA和白内障手术（Phaco-TA）前未进行过小梁切除术（I组），29只眼睛在接受过小梁切除术后进行了Phaco-TA（II组），10只眼睛在接受过小梁切除术后单独接受了TA（III组）。在整个队列中，TA 术后中位眼压立即下降，并在 36 个月内一直显著低于基线值。同样，在整个期间，抗青光眼药物的中位数也有所减少。与此同时，I 组的中位眼压和抗青光眼药物数量在 36 个月内也有所减少。相比之下，小梁切除术后组（II 组和 III 组）的中位眼压和抗青光眼药物用量均未能减少。在接受 Phaco-TA 并同时接受或不接受小梁切除术的患者（第一组和第二组）中，大多数人在随访期间都不需要进一步的手术治疗，而几乎所有在接受小梁切除术后单独接受 TA 的患者（第三组）都需要手术治疗，其中大多数人是在接受 TA 后的第二年到第三年之间。结论是Phaco-TA 具有有效的中期降压和省药效果，尤其是在未接受过小梁切除术的患者中。在小梁切除术后的眼睛中，TA 的效果虽然有限，但仍足以延缓一些患者接受更具侵入性的手术治疗。
{"title":"The Effect of Trabecular Aspiration on Intraocular Pressure, Medication and the Need for Further Glaucoma Surgery in Eyes with Pseudoexfoliation Glaucoma","authors":"Verena Prokosch, Sarah B. Zwingelberg, Desislava V. Efremova, Francesco Buonfiglio, Norbert Pfeiffer, Adrian Gericke","doi":"10.3390/diseases12050092","DOIUrl":"https://doi.org/10.3390/diseases12050092","url":null,"abstract":"Purpose: To investigate whether trabecular aspiration (TA) has an effective medium-term intraocular pressure (IOP)-lowering and medication-saving effect in patients with pseudoexfoliation glaucoma (PEG). In addition, a subgroup analysis of patients with or without a previous trabeculectomy was performed. Methods: Records of 290 consecutive eyes with PEG that underwent TA between 2006 and 2012 at the Department of Ophthalmology, Mainz, Germany, were retrospectively analyzed with a follow-up period of 3 years. The main outcomes were IOP and the need for further medical treatment. Results: Of the 290 eyes with PEG that received TA, 167 eyes from 127 patients met the inclusion criteria. Among these eyes, 128 received TA and cataract surgery (Phaco-TA) without having had a trabeculectomy (group I) before, 29 had Phaco-TA after a previous trabeculectomy (group II) and 10 underwent stand-alone TA after a previous trabeculectomy (group III). In the whole cohort, the median IOP decreased immediately after TA and remained significantly lower compared to the baseline throughout the period of 36 months. Likewise, the median number of antiglaucoma drugs was reduced over the whole period. At the same time, in group I, the median IOP and the number of antiglaucoma drugs were reduced over 36 months. In contrast, in the post-trabeculectomy groups (group II and III), the median IOP and the number of antiglaucoma drugs could not be reduced. While most of the patients that received Phaco-TA with or without a previous trabeculectomy (group I and II) did not require further surgical intervention during the follow-up period, almost all patients receiving stand-alone TA after a previous trabeculectomy (group III) needed surgical therapy, most of them between the second and the third year following TA. Conclusions: Phaco-TA has an effective medium-term pressure-lowering and medication-saving effect, especially in patients without a previous trabeculectomy. In trabeculectomized eyes, the effect of TA is limited but still large enough to delay more invasive surgical interventions in some patients.","PeriodicalId":11200,"journal":{"name":"Diseases","volume":"33 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141010796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-06DOI: 10.3390/diseases12050093
Pratik Mohanty, Babita Pande, Rakesh Acharya, L. Bhaskar, H. Verma
Lung cancer, characterized by its heterogeneity, presents a significant challenge in therapeutic management, primarily due to the development of resistance to conventional drugs. This resistance is often compounded by the tumor’s ability to reprogram its metabolic pathways, a survival strategy that enables cancer cells to thrive in adverse conditions. This review article explores the complex link between drug resistance and metabolic reprogramming in lung cancer, offering a detailed analysis of the molecular mechanisms and treatment strategies. It emphasizes the interplay between drug resistance and changes in metabolic pathways, crucial for developing effective lung cancer therapies. This review examines the impact of current treatments on metabolic pathways and the significance of considering metabolic factors to combat drug resistance. It highlights the different challenges and metabolic alterations in non-small-cell lung cancer and small-cell lung cancer, underlining the need for subtype-specific treatments. Key signaling pathways, including PI3K/AKT/mTOR, MAPK, and AMPK, have been discussed for their roles in promoting drug resistance and metabolic changes, alongside the complex regulatory networks involved. This review article evaluates emerging treatments targeting metabolism, such as metabolic inhibitors, dietary management, and combination therapies, assessing their potential and challenges. It concludes with insights into the role of precision medicine and metabolic biomarkers in crafting personalized lung cancer treatments, advocating for metabolic targeting as a promising approach to enhance treatment efficacy and overcome drug resistance. This review underscores ongoing advancements and hurdles in integrating metabolic considerations into lung cancer therapy strategies.
{"title":"Unravelling the Triad of Lung Cancer, Drug Resistance, and Metabolic Pathways","authors":"Pratik Mohanty, Babita Pande, Rakesh Acharya, L. Bhaskar, H. Verma","doi":"10.3390/diseases12050093","DOIUrl":"https://doi.org/10.3390/diseases12050093","url":null,"abstract":"Lung cancer, characterized by its heterogeneity, presents a significant challenge in therapeutic management, primarily due to the development of resistance to conventional drugs. This resistance is often compounded by the tumor’s ability to reprogram its metabolic pathways, a survival strategy that enables cancer cells to thrive in adverse conditions. This review article explores the complex link between drug resistance and metabolic reprogramming in lung cancer, offering a detailed analysis of the molecular mechanisms and treatment strategies. It emphasizes the interplay between drug resistance and changes in metabolic pathways, crucial for developing effective lung cancer therapies. This review examines the impact of current treatments on metabolic pathways and the significance of considering metabolic factors to combat drug resistance. It highlights the different challenges and metabolic alterations in non-small-cell lung cancer and small-cell lung cancer, underlining the need for subtype-specific treatments. Key signaling pathways, including PI3K/AKT/mTOR, MAPK, and AMPK, have been discussed for their roles in promoting drug resistance and metabolic changes, alongside the complex regulatory networks involved. This review article evaluates emerging treatments targeting metabolism, such as metabolic inhibitors, dietary management, and combination therapies, assessing their potential and challenges. It concludes with insights into the role of precision medicine and metabolic biomarkers in crafting personalized lung cancer treatments, advocating for metabolic targeting as a promising approach to enhance treatment efficacy and overcome drug resistance. This review underscores ongoing advancements and hurdles in integrating metabolic considerations into lung cancer therapy strategies.","PeriodicalId":11200,"journal":{"name":"Diseases","volume":"8 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141006507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-06DOI: 10.3390/diseases12050094
Benedetta Tirone, Gerardo Cazzato, F. Ambrogio, C. Foti, Marco Bellino
Lichen amyloidosis (LA) is a type of cutaneous amyloidosis characterized by brownish hyperkeratotic and itchy papules on the lower leg, back, forearm, or thigh. It is associated with itching and atopic dermatitis (AD) according to an etiopathogenetic mechanism that has not yet been fully elucidated. Currently, the available therapies for this condition include oral antihistamines, laser, cyclosporine, topical corticosteroids, and phototherapy, but, in light of the overlap with AD, Dupilumab may also be indicated. We report the case of a female, 52 years old, who had been suffering from AD and LA for about 27 years. She had lesions attributable to both diseases on the trunk and lower limbs associated with severe itching and had proved resistant to cyclosporine therapy. It was decided to opt for Dupilumab with the induction of 2 fl of 300 mg and maintenance with 1 fl every other week. The therapy proved to be effective, returning a total resolution of both diseases one year after the beginning of the treatment. Dupilumab demonstrated efficacy and safety in the LA related to AD and led to clinical and quality of life improvements in this patient. Therefore, Dupilumab should be considered when treating LA. Further studies should be conducted focusing on the efficacy of the drug on LA (whether or not related to AD), changes in the skin lesions after discontinuation, and the safety of long-term application.
苔癣淀粉样变性（LA）是一种皮肤淀粉样变性病，其特征是小腿、背部、前臂或大腿上出现褐色角化过度和瘙痒的丘疹。它与瘙痒和特应性皮炎（AD）有关，其发病机制尚未完全阐明。目前，治疗该病的方法包括口服抗组胺药、激光、环孢素、局部皮质类固醇激素和光疗，但鉴于该病与特应性皮炎重叠，杜匹单抗也可能适用。我们报告了一例女性患者的病例，她 52 岁，患有 AD 和 LA 约 27 年。她的躯干和下肢同时患有这两种疾病，并伴有严重的瘙痒，对环孢素治疗产生了耐药性。医生决定使用杜比鲁单抗，诱导剂量为 2 瓶 300 毫克，维持剂量为每隔一周 1 瓶。事实证明，这种疗法非常有效，在治疗开始一年后，两种疾病都得到了完全治愈。杜匹单抗对与注意力缺失症有关的 LA 具有疗效和安全性，并改善了该患者的临床和生活质量。因此，在治疗 LA 时应考虑使用杜匹单抗。应进一步研究该药物对 LA（无论是否与 AD 有关）的疗效、停药后皮损的变化以及长期应用的安全性。
{"title":"Lichen Amyloidosis in an Atopic Patient Treated with Dupilumab: A New Therapeutic Option","authors":"Benedetta Tirone, Gerardo Cazzato, F. Ambrogio, C. Foti, Marco Bellino","doi":"10.3390/diseases12050094","DOIUrl":"https://doi.org/10.3390/diseases12050094","url":null,"abstract":"Lichen amyloidosis (LA) is a type of cutaneous amyloidosis characterized by brownish hyperkeratotic and itchy papules on the lower leg, back, forearm, or thigh. It is associated with itching and atopic dermatitis (AD) according to an etiopathogenetic mechanism that has not yet been fully elucidated. Currently, the available therapies for this condition include oral antihistamines, laser, cyclosporine, topical corticosteroids, and phototherapy, but, in light of the overlap with AD, Dupilumab may also be indicated. We report the case of a female, 52 years old, who had been suffering from AD and LA for about 27 years. She had lesions attributable to both diseases on the trunk and lower limbs associated with severe itching and had proved resistant to cyclosporine therapy. It was decided to opt for Dupilumab with the induction of 2 fl of 300 mg and maintenance with 1 fl every other week. The therapy proved to be effective, returning a total resolution of both diseases one year after the beginning of the treatment. Dupilumab demonstrated efficacy and safety in the LA related to AD and led to clinical and quality of life improvements in this patient. Therefore, Dupilumab should be considered when treating LA. Further studies should be conducted focusing on the efficacy of the drug on LA (whether or not related to AD), changes in the skin lesions after discontinuation, and the safety of long-term application.","PeriodicalId":11200,"journal":{"name":"Diseases","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141007326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-05DOI: 10.3390/diseases12050089
Fadila Bousgheiri, Ali Allouch, K. Sammoud, Rut Navarro-Martínez, Vanessa Ibáñez-del Valle, M. Senhaji, Omar Cauli, N. El Mlili, Adil Najdi
Poor sleep quality, a global public health concern, poses a significant burden on individuals, particularly health care university students facing intense academic stress. A three-center cross-sectional study was conducted at the Higher Institute of Nursing and Health Sciences in Tetouan (Morocco), Faculty of Medicine in Tangier (Morocco) and Faculty of Nursing in Valencia (Spain). We collected various data using a sociodemographic questionnaire, the Pittsburgh sleep quality questionnaire, the international physical activity questionnaire (IPAQ) and the smartphone addiction questionnaire short-version (SAS-SV). A total of 1210 students were included in our study (mean age 20.4 years, 67.2% female, nursing students (66.2%) and medical students (33.8%), 76.1% students from Morocco and 33.9% from Spain). Analysis revealed a higher prevalence of poor sleep quality among Moroccans students compared to Spanish ones (p < 0.001), that nursing students showed less favorable sleep quality than medical students (p < 0.011) and that living with a chronic disease was linked to less favorable sleep quality (p < 0.001). Lastly, intense or weak physical activity and smartphone addiction were correlated with poor sleep quality (p < 0.001). In the multivariate analysis, an association persisted between poor sleep quality and factors such as the country of study (Odds ratio (OR): 6.25 [95% Confidence Interval (CI): 4.34–9.09]), involvement in nursing studies (OR: 3.50 [95% CI: 2.36–5.27]), and the presence of chronic diseases (OR: 2.70 [95% CI: 1.72–4.16]), (p < 0.01 each). Our findings highlight the multifaceted factors affecting sleep quality in young university students. The implications underscore the imperative of interventions tailored to this demographic group.
{"title":"Factors Affecting Sleep Quality among University Medical and Nursing Students: A Study in Two Countries in the Mediterranean Region","authors":"Fadila Bousgheiri, Ali Allouch, K. Sammoud, Rut Navarro-Martínez, Vanessa Ibáñez-del Valle, M. Senhaji, Omar Cauli, N. El Mlili, Adil Najdi","doi":"10.3390/diseases12050089","DOIUrl":"https://doi.org/10.3390/diseases12050089","url":null,"abstract":"Poor sleep quality, a global public health concern, poses a significant burden on individuals, particularly health care university students facing intense academic stress. A three-center cross-sectional study was conducted at the Higher Institute of Nursing and Health Sciences in Tetouan (Morocco), Faculty of Medicine in Tangier (Morocco) and Faculty of Nursing in Valencia (Spain). We collected various data using a sociodemographic questionnaire, the Pittsburgh sleep quality questionnaire, the international physical activity questionnaire (IPAQ) and the smartphone addiction questionnaire short-version (SAS-SV). A total of 1210 students were included in our study (mean age 20.4 years, 67.2% female, nursing students (66.2%) and medical students (33.8%), 76.1% students from Morocco and 33.9% from Spain). Analysis revealed a higher prevalence of poor sleep quality among Moroccans students compared to Spanish ones (p < 0.001), that nursing students showed less favorable sleep quality than medical students (p < 0.011) and that living with a chronic disease was linked to less favorable sleep quality (p < 0.001). Lastly, intense or weak physical activity and smartphone addiction were correlated with poor sleep quality (p < 0.001). In the multivariate analysis, an association persisted between poor sleep quality and factors such as the country of study (Odds ratio (OR): 6.25 [95% Confidence Interval (CI): 4.34–9.09]), involvement in nursing studies (OR: 3.50 [95% CI: 2.36–5.27]), and the presence of chronic diseases (OR: 2.70 [95% CI: 1.72–4.16]), (p < 0.01 each). Our findings highlight the multifaceted factors affecting sleep quality in young university students. The implications underscore the imperative of interventions tailored to this demographic group.","PeriodicalId":11200,"journal":{"name":"Diseases","volume":"353 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141012062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-05DOI: 10.3390/diseases12050090
Oliwia Szymanowicz, Artur Drużdż, B. Słowikowski, Sandra Pawlak, Ewelina Potocka, Ulyana Goutor, Mateusz Konieczny, Małgorzata Ciastoń, Aleksandra Lewandowska, Paweł P. Jagodziński, W. Kozubski, J. Dorszewska
Calcium channels are specialized ion channels exhibiting selective permeability to calcium ions. Calcium channels, comprising voltage-dependent and ligand-gated types, are pivotal in neuronal function, with their dysregulation is implicated in various neurological disorders. This review delves into the significance of the CACNA genes, including CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1G, and CACNA1H, in the pathogenesis of conditions such as migraine, epilepsy, cerebellar ataxia, dystonia, and cerebellar atrophy. Specifically, variants in CACNA1A have been linked to familial hemiplegic migraine and epileptic seizures, underscoring its importance in neurological disease etiology. Furthermore, different genetic variants of CACNA1B have been associated with migraine susceptibility, further highlighting the role of CACNA genes in migraine pathology. The complex relationship between CACNA gene variants and neurological phenotypes, including focal seizures and ataxia, presents a variety of clinical manifestations of impaired calcium channel function. The aim of this article was to explore the role of CACNA genes in various neurological disorders, elucidating their significance in conditions such as migraine, epilepsy, and cerebellar ataxias. Further exploration of CACNA gene variants and their interactions with molecular factors, such as microRNAs, holds promise for advancing our understanding of genetic neurological disorders.
{"title":"A Review of the CACNA Gene Family: Its Role in Neurological Disorders","authors":"Oliwia Szymanowicz, Artur Drużdż, B. Słowikowski, Sandra Pawlak, Ewelina Potocka, Ulyana Goutor, Mateusz Konieczny, Małgorzata Ciastoń, Aleksandra Lewandowska, Paweł P. Jagodziński, W. Kozubski, J. Dorszewska","doi":"10.3390/diseases12050090","DOIUrl":"https://doi.org/10.3390/diseases12050090","url":null,"abstract":"Calcium channels are specialized ion channels exhibiting selective permeability to calcium ions. Calcium channels, comprising voltage-dependent and ligand-gated types, are pivotal in neuronal function, with their dysregulation is implicated in various neurological disorders. This review delves into the significance of the CACNA genes, including CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1G, and CACNA1H, in the pathogenesis of conditions such as migraine, epilepsy, cerebellar ataxia, dystonia, and cerebellar atrophy. Specifically, variants in CACNA1A have been linked to familial hemiplegic migraine and epileptic seizures, underscoring its importance in neurological disease etiology. Furthermore, different genetic variants of CACNA1B have been associated with migraine susceptibility, further highlighting the role of CACNA genes in migraine pathology. The complex relationship between CACNA gene variants and neurological phenotypes, including focal seizures and ataxia, presents a variety of clinical manifestations of impaired calcium channel function. The aim of this article was to explore the role of CACNA genes in various neurological disorders, elucidating their significance in conditions such as migraine, epilepsy, and cerebellar ataxias. Further exploration of CACNA gene variants and their interactions with molecular factors, such as microRNAs, holds promise for advancing our understanding of genetic neurological disorders.","PeriodicalId":11200,"journal":{"name":"Diseases","volume":"319 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141012507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03DOI: 10.3390/diseases12050088
A. ali, R. Caldwell, G. Pina, Noah Beinart, Garrett Jensen, Syed Wamique Yusuf, E. Koutroumpakis, Ihab Hamzeh, Shaden Khalaf, Cezar A Iliescu, Anita M Deswal, Nicolas L. Palaskas
Introduction: The impact of peripheral cytokine levels on the prognosis and treatment of immune checkpoint inhibitor (ICI) myocarditis has not been well studied. Objectives: This study aimed to identify cytokines that can prognosticate and direct the treatment of ICI myocarditis. Methods: This was a single-center, retrospective cohort study of patients with ICI myocarditis who had available peripheral cytokine levels between January 2011 and May 2022. Major adverse cardiovascular events (MACEs) were defined as a composite of heart failure with/without cardiogenic shock, arterial thrombosis, life-threatening arrhythmias, pulmonary embolism, and sudden cardiac death. Results: In total, 65 patients with ICI myocarditis had cytokine data available. Patients were mostly males (70%), with a mean age of 67.8 ± 12.7 years. Interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) were the most common cytokines to be elevated with 48/65 (74%) of patients having a peak IL-6 above normal limits (>5 pg/mL) and 44/65 (68%) of patients with peak TNF-α above normal limits (>22 pg/mL). Patients with elevated peak IL-6 had similar 90-day mortality and MACE outcomes compared to those without (10.4% vs. 11.8%, p = 0.878 and 8.8% vs. 17.7%, p = 0.366, respectively). Similarly, those with elevated peak TNF-α had similar 90-day mortality and MACEs compared to those without (29.6% vs. 14.3%, p = 0.182 and 13.6% vs. 4.8%, p = 0.413, respectively). Kaplan–Meier survival analysis also showed that there was not a significant difference between MACE-free survival when comparing elevated and normal IL-6 and TNF-α levels (p = 0.182 and p = 0.118, respectively). MACEs and overall survival outcomes were similar between those who received infliximab and those who did not among all patients and those with elevated TNF-α (p-value 0.70 and 0.83, respectively). Conclusion: Peripheral blood levels of IL-6 and TNF-α are the most commonly elevated cytokines in patients with ICI myocarditis. However, their role in the prognostication and guidance of immunomodulatory treatment is currently limited.
简介外周细胞因子水平对免疫检查点抑制剂（ICI）心肌炎预后和治疗的影响尚未得到充分研究。本研究旨在确定细胞因子对心肌炎预后和治疗的影响：本研究旨在确定可预测 ICI 心肌炎预后并指导治疗的细胞因子。研究方法这是一项单中心、回顾性队列研究，研究对象为2011年1月至2022年5月期间可获得外周细胞因子水平的ICI心肌炎患者。主要不良心血管事件（MACEs）定义为合并/不合并心源性休克的心力衰竭、动脉血栓形成、危及生命的心律失常、肺栓塞和心脏性猝死的综合征。结果共有 65 名 ICI 心肌炎患者的细胞因子数据可用。患者多为男性（70%），平均年龄（67.8 ± 12.7）岁。白细胞介素（IL）-6和肿瘤坏死因子-α（TNF-α）是最常见的升高细胞因子，48/65（74%）的患者IL-6峰值超过正常值（>5 pg/mL），44/65（68%）的患者TNF-α峰值超过正常值（>22 pg/mL）。IL-6峰值升高的患者与未升高的患者相比，90天死亡率和MACE结果相似（分别为10.4% vs. 11.8%，p = 0.878和8.8% vs. 17.7%，p = 0.366）。同样，TNF-α峰值升高者与未升高者的90天死亡率和MACE相似（分别为29.6% vs. 14.3%，p = 0.182和13.6% vs. 4.8%，p = 0.413）。Kaplan-Meier生存分析还显示，IL-6和TNF-α水平升高与正常相比，无MACE生存率没有显著差异（分别为p = 0.182和p = 0.118）。在所有患者和TNF-α水平升高的患者中，接受英夫利昔单抗治疗和未接受英夫利昔单抗治疗的患者的MACE和总生存率结果相似（P值分别为0.70和0.83）。结论IL-6和TNF-α是ICI心肌炎患者外周血中最常升高的细胞因子。然而，它们在预后和指导免疫调节治疗方面的作用目前还很有限。
{"title":"Elevated IL-6 and Tumor Necrosis Factor-α in Immune Checkpoint Inhibitor Myocarditis","authors":"A. ali, R. Caldwell, G. Pina, Noah Beinart, Garrett Jensen, Syed Wamique Yusuf, E. Koutroumpakis, Ihab Hamzeh, Shaden Khalaf, Cezar A Iliescu, Anita M Deswal, Nicolas L. Palaskas","doi":"10.3390/diseases12050088","DOIUrl":"https://doi.org/10.3390/diseases12050088","url":null,"abstract":"Introduction: The impact of peripheral cytokine levels on the prognosis and treatment of immune checkpoint inhibitor (ICI) myocarditis has not been well studied. Objectives: This study aimed to identify cytokines that can prognosticate and direct the treatment of ICI myocarditis. Methods: This was a single-center, retrospective cohort study of patients with ICI myocarditis who had available peripheral cytokine levels between January 2011 and May 2022. Major adverse cardiovascular events (MACEs) were defined as a composite of heart failure with/without cardiogenic shock, arterial thrombosis, life-threatening arrhythmias, pulmonary embolism, and sudden cardiac death. Results: In total, 65 patients with ICI myocarditis had cytokine data available. Patients were mostly males (70%), with a mean age of 67.8 ± 12.7 years. Interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) were the most common cytokines to be elevated with 48/65 (74%) of patients having a peak IL-6 above normal limits (>5 pg/mL) and 44/65 (68%) of patients with peak TNF-α above normal limits (>22 pg/mL). Patients with elevated peak IL-6 had similar 90-day mortality and MACE outcomes compared to those without (10.4% vs. 11.8%, p = 0.878 and 8.8% vs. 17.7%, p = 0.366, respectively). Similarly, those with elevated peak TNF-α had similar 90-day mortality and MACEs compared to those without (29.6% vs. 14.3%, p = 0.182 and 13.6% vs. 4.8%, p = 0.413, respectively). Kaplan–Meier survival analysis also showed that there was not a significant difference between MACE-free survival when comparing elevated and normal IL-6 and TNF-α levels (p = 0.182 and p = 0.118, respectively). MACEs and overall survival outcomes were similar between those who received infliximab and those who did not among all patients and those with elevated TNF-α (p-value 0.70 and 0.83, respectively). Conclusion: Peripheral blood levels of IL-6 and TNF-α are the most commonly elevated cytokines in patients with ICI myocarditis. However, their role in the prognostication and guidance of immunomodulatory treatment is currently limited.","PeriodicalId":11200,"journal":{"name":"Diseases","volume":"56 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141016709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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