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J. Pers. Med., Volume 11, Issue 12 (December 2021) – 149 articles

Cover Story (view full-size image): A person high in neuroticism is more likely to experience anxiety, stress, worry, fear, anger, and depression. It is known that gut microbiota can influence personality and mental disorders, including stress, anxiety, and depression, through the gut–brain axis. Here, we investigated correlations between the subfacets of neuroticism and gut microbiota using the Revised NEO Personality Inventory and the 16S rRNA gene sequencing data of 784 Korean adults. Our findings will contribute to uncovering the potential link between gut microbiota and neuroticism, and the elucidation of the correlations of the microbiome–gut–brain axis with behavioral changes and psychiatric cases in the general population. View this paper
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Article
Multiparametric Ultrasound Approach Using a Tree-Based Decision Classifier for Inconclusive Focal Liver Lesions Evaluated by Contrast Enhanced Ultrasound
J. Pers. Med. 2021, 11(12), 1388; https://doi.org/10.3390/jpm11121388 - 20 Dec 2021
Viewed by 890
Abstract
Background: Multiparametric ultrasound (MPUS) is a concept whereby the examiner is encouraged to use the latest features of an ultrasound machine. The aim of this study was to reanalyze inconclusive focal liver lesions (FLLs) that had been analyzed via contrast enhanced ultrasound (CEUS) [...] Read more.
Background: Multiparametric ultrasound (MPUS) is a concept whereby the examiner is encouraged to use the latest features of an ultrasound machine. The aim of this study was to reanalyze inconclusive focal liver lesions (FLLs) that had been analyzed via contrast enhanced ultrasound (CEUS) using the MPUS approach with the help of a tree-based decision classifier. Materials and methods: We retrospectively analyzed FLLs that were inconclusive upon CEUS examination in our department, focusing our attention on samples taken over a period of two years (2017−2018). MPUS reanalysis followed a three-step algorithm, taking into account the liver stiffness measurement (LSM), time–intensity curve analysis (TIC), and parametric imaging (PI). After processing all steps of the algorithm, a binary decision tree classifier (BDTC) was used to achieve a software-assisted decision. Results: Area was the only TIC-CEUS parameter that showed a significant difference between malign and benign lesions with a cutoff of >−19.3 dB for washout phenomena (AUROC = 0.58, Se = 74.0%, Sp = 45.7%). Using the binary decision tree classifier (BDTC) algorithm, we correctly classified 71 out of 91 lesions according to their malignant or benignant status, with an accuracy of 78.0% (sensitivity = 62%, specificity = 45%, and precision = 80%). Conclusions: By reevaluating inconclusive FLLs that had been analyzed via CEUS using MPUS, we managed to determine that 78% of the lesions were malignant and, in 28% of them, we established the lesion type. Full article
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Article
Assessment of Sleep among Patients with Chronic Liver Disease: Association with Quality of Life
J. Pers. Med. 2021, 11(12), 1387; https://doi.org/10.3390/jpm11121387 - 20 Dec 2021
Cited by 3 | Viewed by 930
Abstract
The present study aims to assess the sleep characteristics and health-related quality of life (HRQOL) among patients with chronic liver diseases (CLDs), as well as the relationship between them. We conducted a prospective cross-sectional study, over a period of eight months, on patients [...] Read more.
The present study aims to assess the sleep characteristics and health-related quality of life (HRQOL) among patients with chronic liver diseases (CLDs), as well as the relationship between them. We conducted a prospective cross-sectional study, over a period of eight months, on patients with CLDs. Sleep was assessed by subjective tools (self-reported validated questionnaires), semi-objective methods (actigraphy), and HRQOL by using the 36-Item Short Form Survey (SF-36) and Chronic Liver Disease Questionnaire (CLDQ). The results indicated that 48.21% of patients with CLDs had a mean Pittsburgh Sleep Quality Index (PSQI) score higher than five, suggestive of poor sleep; 39.29% of patients had a mean Epworth Sleepiness Scale (ESS) score ≥11, indicative of daytime sleepiness. Actigraphy monitoring showed that patients with cirrhosis had significantly more delayed bedtime hours and get-up hours, more awakenings, and more reduced sleep efficacy when compared to pre-cirrhotics. The CLDQ and SF-36 questionnaire scores were significantly lower in cirrhotics compared to pre-cirrhotics within each domain. Moreover, we identified significant correlations between the variables from each questionnaire, referring to HRQOL and sleep parameters. In conclusion, sleep disturbances are commonly encountered among patients with CLDs and are associated with impaired HRQOL. This is the first study in Romania that assesses sleep by actigraphy in a cohort of patients with different stages of CLD. Full article
(This article belongs to the Special Issue Personalized Care and Treatment Compliance in Chronic Conditions)
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Article
Risk of Dementia in Patients Who Underwent Surgery under Neuraxial Anesthesia: A Nationwide Cohort Study
J. Pers. Med. 2021, 11(12), 1386; https://doi.org/10.3390/jpm11121386 - 20 Dec 2021
Cited by 1 | Viewed by 910
Abstract
The incidence of dementia in patients with surgery under neuraxial anesthesia and the possibility of surgery under neuraxial anesthesia as a risk factor for dementia were investigated. We performed a retrospective matched cohort study with nationwide, representative cohort sample data of the Korean [...] Read more.
The incidence of dementia in patients with surgery under neuraxial anesthesia and the possibility of surgery under neuraxial anesthesia as a risk factor for dementia were investigated. We performed a retrospective matched cohort study with nationwide, representative cohort sample data of the Korean National Health Insurance Service in South Korea between 1 January 2003, and 31 December 2004. The participants were divided into control (n = 4488) and neuraxial groups (n = 1122) using propensity score matching. After 9 years of follow-up, the corresponding incidences of dementia were 11.5 and 14.8 cases per 1000 person-years. The risk of dementia in the surgery under neuraxial group was 1.44-fold higher (95% confidence interval [95%CI], 1.17–1.76) than that in the control group. In the subgroup analysis of dementia, the risk of Alzheimer’s disease in those who underwent surgery under neuraxial anesthesia was 1.48-fold higher (95%CI, 1.17–1.87) than that in those who did not undergo surgery under anesthesia. Our findings suggest that patients who underwent surgery under neuraxial anesthesia had a higher risk of dementia and Alzheimer’s disease than those who did not undergo surgery under neuraxial anesthesia. Full article
(This article belongs to the Section Epidemiology)
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Article
Precision Medicine in Aortic Anastomosis: A Numerical and Experimental Study of a Novel Double-Sided Needle
J. Pers. Med. 2021, 11(12), 1385; https://doi.org/10.3390/jpm11121385 - 20 Dec 2021
Viewed by 885
Abstract
Background: Hand-sewn anastomosis is a crucial part of aortic reconstruction surgery and significantly affects its outcome. The present study presents a novel, bidirectional surgical needle aimed to improve aortic anastomosis in terms of speed and ease of use. Our objective was to assess [...] Read more.
Background: Hand-sewn anastomosis is a crucial part of aortic reconstruction surgery and significantly affects its outcome. The present study presents a novel, bidirectional surgical needle aimed to improve aortic anastomosis in terms of speed and ease of use. Our objective was to assess the efficacy of the new design in comparison with the conventional needle. Methods: A series of simulations were conducted with COMSOL software in order to perform a fatigue comparative analysis between the new and the conventional needle design. Ease of penetration into a piece of polydimethylsiloxane was evaluated. Lastly, the prototype was tested under in-vitro conditions in comparison with the conventional needle. Results: Based on fatigue analysis, the new needle design improves durability, provided the two tips are equally used. The polytetrafluoroethylene coating improves penetration into the tissue by 7% to 17%, while electropolishing improves penetration up to 19%. When using the novel needle design, the average anastomotic task completion time was significantly reduced by 22% and the overall distance of hand movements was significantly reduced by 20%. Conclusions: The proposed design exhibited a shorter anastomotic time and seems promising in relation to ease of use and simplicity of the anastomotic technique it introduces. Full article
(This article belongs to the Special Issue Therapeutic Targets and Personalized Medicine in Cardiac Disease)
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Article
Prognostic Value of Histone Modifying Enzyme EZH2 in RCHOP-Treated Diffuse Large B-Cell Lymphoma and High Grade B-Cell Lymphoma
J. Pers. Med. 2021, 11(12), 1384; https://doi.org/10.3390/jpm11121384 - 18 Dec 2021
Viewed by 1014
Abstract
Background: DLBCL represent a heterogeneous group of aggressive diseases. High grade B-cell lymphomas (HGBCL) were recently individualized from DLBCL as a discrete diagnostic entity due to their worse prognosis. Currently, although most patients are successfully treated with RCHOP regimens, 1/3 will either not [...] Read more.
Background: DLBCL represent a heterogeneous group of aggressive diseases. High grade B-cell lymphomas (HGBCL) were recently individualized from DLBCL as a discrete diagnostic entity due to their worse prognosis. Currently, although most patients are successfully treated with RCHOP regimens, 1/3 will either not respond or ultimately relapse. Alterations in histone modifying enzymes have emerged as the most common alterations in DLBCL, but their role as prognostic biomarkers is controversial. We aimed to ascertain the prognostic value of EZH2 immunoexpression in RCHOP-treated DLBCL and HGBCL. Results: We performed a retrospective cohort study including 125 patients with RCHOP-treated DLBCL or HGBCL. EZH2 expression levels did not differ between diagnostic groups or between DLBCL-NOS molecular groups. We found no associations between EZH2 expression levels and outcome, including in the subgroup analysis (GC versus non-GC). Nonetheless, EZH2/BCL2 co-expression was significantly associated with worse outcome (event free survival and overall survival). Conclusion: Although EZH2 mutations are almost exclusively found in GC-DLBCL, we found similar EZH2 expression levels in both DLBCL-NOS molecular groups, suggesting non-mutational mechanisms of EZH2 deregulation. These findings suggest that the use of EZH2 antagonists might be extended to non-GC DLBCL patients with clinical benefit. EZH2/BCL2 co-expression was associated with a worse outcome. Full article
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Review
Equity or Equality? Which Approach Brings More Satisfaction in a Kidney-Exchange Chain?
J. Pers. Med. 2021, 11(12), 1383; https://doi.org/10.3390/jpm11121383 - 18 Dec 2021
Viewed by 815
Abstract
In United States (U.S.), government-funded organizations, such as NLDAC, reimburse travel and subsistence expenses incurred during living-organ donation process. However, in Iran, there is a non-governmental organization called Iranian Kidney Foundation (IKF) that funds the direct and indirect costs of donors through charitable [...] Read more.
In United States (U.S.), government-funded organizations, such as NLDAC, reimburse travel and subsistence expenses incurred during living-organ donation process. However, in Iran, there is a non-governmental organization called Iranian Kidney Foundation (IKF) that funds the direct and indirect costs of donors through charitable donations and contributions from participants in the exchange program. In this article, for countries outside the U.S. that currently use an equality approach, we propose a potential new compensation-apportionment approach (equitable approach) for kidney-exchange chains and compare it with the currently available system (equality approach) in terms of the apportionment of compensation in a kidney-exchange chain to cover the expenses incurred by the initiating living donor of the chain in the act of donation. To this end, we propose a mechanism to apportion compensation among all participating pairs based on the equity approach by utilizing a prediction model to calculate the probability of graft survival in each transplant operation. These probabilities are then used to define the utility of any transplantation, considering the quality of each pair’s donated and received kidney in the chain. Afterward, the corresponding cost is apportioned by a mechanism based on the normalized differences between the utility of donated and received kidneys for each incompatible pair of the chain. In summary, we demonstrate that by utilizing the equitable approach, there is more fairness and equity in the allocation of resources in organ-procurement systems, which results in more satisfaction among incompatible pairs. Additional future prospective studies are needed to assess this proposed equitable approach for kidney-exchange chains in countries outside the U.S., such as Iran, that currently use an equality approach. Full article
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Article
A Network-Based Analysis of Disease Complication Associations for Obstetric Disorders in the UK Biobank
J. Pers. Med. 2021, 11(12), 1382; https://doi.org/10.3390/jpm11121382 - 17 Dec 2021
Viewed by 924
Abstract
Background: Recent studies have found that women with obstetric disorders are at increased risk for a variety of long-term complications. However, the underlying pathophysiology of these connections remains undetermined. A network-based view incorporating knowledge of other diseases and genetic associations will aid our [...] Read more.
Background: Recent studies have found that women with obstetric disorders are at increased risk for a variety of long-term complications. However, the underlying pathophysiology of these connections remains undetermined. A network-based view incorporating knowledge of other diseases and genetic associations will aid our understanding of the role of genetics in pregnancy-related disease complications. Methods: We built a disease–disease network (DDN) using UK Biobank (UKBB) summary data from a phenome-wide association study (PheWAS) to elaborate multiple disease associations. We also constructed egocentric DDNs, where each network focuses on a pregnancy-related disorder and its neighboring diseases. We then applied graph-based semi-supervised learning (GSSL) to translate the connections in the egocentric DDNs to pathologic knowledge. Results: A total of 26 egocentric DDNs were constructed for each pregnancy-related phenotype in the UKBB. Applying GSSL to each DDN, we obtained complication risk scores for additional phenotypes given the pregnancy-related disease of interest. Predictions were validated using co-occurrences derived from UKBB electronic health records. Our proposed method achieved an increase in average area under the receiver operating characteristic curve (AUC) by a factor of 1.35 from 55.0% to 74.4% compared to the use of the full DDN. Conclusion: Egocentric DDNs hold promise as a clinical tool for the network-based identification of potential disease complications for a variety of phenotypes. Full article
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Article
Gut Microbiota Composition across Normal Range Prostate-Specific Antigen Levels
J. Pers. Med. 2021, 11(12), 1381; https://doi.org/10.3390/jpm11121381 - 17 Dec 2021
Viewed by 946
Abstract
Animal studies have shown the interaction between androgens and the gut microbiome directly and indirectly; however, limited evidence from human studies is available. To evaluate the association between prostate-specific antigen (PSA) levels within the normal range, reflective of androgen receptor activity, and the [...] Read more.
Animal studies have shown the interaction between androgens and the gut microbiome directly and indirectly; however, limited evidence from human studies is available. To evaluate the association between prostate-specific antigen (PSA) levels within the normal range, reflective of androgen receptor activity, and the gut microbiota composition, a cross-sectional analysis was performed in 759 Korean men aged between 25 and 78 years with normal PSA levels of ≤4.0 ng/mL. We evaluated the biodiversity of gut microbiota as well as the taxonomic and functional signatures associated with PSA levels using 16S rRNA gene sequencing data. PSA levels within the normal range were categorized into three groups: lowest quartile (G1), interquartile range (G2, reference), and highest quartile (G3). The G3 group had higher microbial richness than the G2 group, although it was dominated by a few bacteria. An increase in Escherichia/Shigella abundance and a reduction in Megamonas abundance in the G3 group were also detected. A U-shaped relationship was observed between the three groups across most analyses, including biodiversity, taxonomic composition, and inferred pathways in the gut microbiota. This study showed different microbiota patterns across PSA levels within the normal range. Further studies are required to elucidate the role of microbiota in regulating PSA levels. Full article
(This article belongs to the Section Clinical Medicine, Cell, and Organism Physiology)
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Article
Does COVID-19 Clinical Status Associate with Outcome Severity? An Unsupervised Machine Learning Approach for Knowledge Extraction
J. Pers. Med. 2021, 11(12), 1380; https://doi.org/10.3390/jpm11121380 - 17 Dec 2021
Cited by 2 | Viewed by 1124
Abstract
Since the beginning of the COVID-19 pandemic, 195 million people have been infected and 4.2 million have died from the disease or its side effects. Physicians, healthcare scientists and medical staff continuously try to deal with overloaded hospital admissions, while in parallel, they [...] Read more.
Since the beginning of the COVID-19 pandemic, 195 million people have been infected and 4.2 million have died from the disease or its side effects. Physicians, healthcare scientists and medical staff continuously try to deal with overloaded hospital admissions, while in parallel, they try to identify meaningful correlations between the severity of infected patients with their symptoms, comorbidities and biomarkers. Artificial intelligence (AI) and machine learning (ML) have been used recently in many areas related to COVID-19 healthcare. The main goal is to manage effectively the wide variety of issues related to COVID-19 and its consequences. The existing applications of ML to COVID-19 healthcare are based on supervised classifications which require a labeled training dataset, serving as reference point for learning, as well as predefined classes. However, the existing knowledge about COVID-19 and its consequences is still not solid and the points of common agreement among different scientific communities are still unclear. Therefore, this study aimed to follow an unsupervised clustering approach, where prior knowledge is not required (tabula rasa). More specifically, 268 hospitalized patients at the First Propaedeutic Department of Internal Medicine of AHEPA University Hospital of Thessaloniki were assessed in terms of 40 clinical variables (numerical and categorical), leading to a high-dimensionality dataset. Dimensionality reduction was performed by applying a principal component analysis (PCA) on the numerical part of the dataset and a multiple correspondence analysis (MCA) on the categorical part of the dataset. Then, the Bayesian information criterion (BIC) was applied to Gaussian mixture models (GMM) in order to identify the optimal number of clusters under which the best grouping of patients occurs. The proposed methodology identified four clusters of patients with similar clinical characteristics. The analysis revealed a cluster of asymptomatic patients that resulted in death at a rate of 23.8%. This striking result forces us to reconsider the relationship between the severity of COVID-19 clinical symptoms and the patient’s mortality. Full article
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Article
The Role of US in Depicting Axillary Metastasis in High-Risk Breast Cancer Patients
J. Pers. Med. 2021, 11(12), 1379; https://doi.org/10.3390/jpm11121379 - 16 Dec 2021
Cited by 1 | Viewed by 748
Abstract
Purpose: The aim of this study is to evaluate the role of US in depicting axillary nodal disease in high-risk patients with and without pathogenic mutations. Methods: The retrospective study included consecutive high-risk breast cancer (BC) patients who underwent a multigene testing panel [...] Read more.
Purpose: The aim of this study is to evaluate the role of US in depicting axillary nodal disease in high-risk patients with and without pathogenic mutations. Methods: The retrospective study included consecutive high-risk breast cancer (BC) patients who underwent a multigene testing panel for hereditary cancers, pre-operative axillary US and breast/axillary surgery. The group was divided into patients with pathogenic mutations (PM group) and patients without PM. Statistical analyses were performed using GraphPad Prism by applying Chi-square and Fisher exact tests, with a reference p-value < 0.05 and a CI of 95%. Results: Out of 190 patients with BC, 96 (51%) were negative and 94 (49%) were positive for PM as follows: 28 (25.5%) BRCA1, 16 (17%) BRCA2, 15 (16%) CHECK2, 14 (14%) RAD Group, 7 (7%) PALB, 6 (6%) NBN, 3 (3%) TP53 and ATM and 2 (2%) BARD1. US was positive in 88 of the patients, 36 with PM and 52 without PM. US and surgery (≥N1 stage) were both positive in 31 (62%) of PM patients and 44 (88%) of patients without genetic changes. There were 19 (61%) false negative US examinations in the PM group and 6 (13%) in the group without genetic changes, respectively. If the US is positive, there is a 2.6 times greater risk of positive nodes in PM patients (p-value < 0.000, 95% CI = 4.2–37.9), and a 6.2 times greater risk of positive nodes in patients without genetic changes (p-value < 0.000, 95%CI = 8.4–37.4). In the PM group, US compared to surgery reached a sensitivity = 62, with PPV = 86 and NPV = 67. In the BRCA1/2 subgroup, there is 2.5 greater times risk of nodal disease if the US is positive (p-value = 0.001, 95%CI = 2.6–76). In patients without PM, US compared to surgery reached a sensitivity = 88, PPV = 84 and NPV = 86. Conclusion: US is more sensitive in depicting axillary nodal disease in high-risk patients without PM compared to PM patients. Furthermore, there are more false negative US examinations in PM patients, compared to surgery patients. Full article
(This article belongs to the Topic eHealth and mHealth: Challenges and Prospects)
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Article
Association of Polymorphisms in Plasminogen Activator Inhibitor-1 (PAI-1), Tissue Plasminogen Activator (tPA), and Renin (REN) with Recurrent Pregnancy Loss in Korean Women
J. Pers. Med. 2021, 11(12), 1378; https://doi.org/10.3390/jpm11121378 - 16 Dec 2021
Cited by 2 | Viewed by 792
Abstract
Recurrent pregnancy loss (RPL) is defined as two or more consecutive pregnancy losses prior to 20 weeks of gestational age. Various factors, including immune dysfunction, endocrine disorders, coagulation abnormality, and genetic disorders influence RPL. In particular, plasminogen activator inhibitor-1 (PAI-1), tissue [...] Read more.
Recurrent pregnancy loss (RPL) is defined as two or more consecutive pregnancy losses prior to 20 weeks of gestational age. Various factors, including immune dysfunction, endocrine disorders, coagulation abnormality, and genetic disorders influence RPL. In particular, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA), and renin (REN) have important roles in the thrombotic and thrombolytic systems, and abnormal expression of these genes have a reported negative correlation with pregnancy maintenance. Moreover, some polymorphisms of the three genes are related to expression levels and thrombotic disorder. Therefore, we investigated whether polymorphisms of PAI-1, tPA, and REN are linked to RPL. Genotyping of the six polymorphisms (PAI-1 rs11178, rs1050955, tPA rs4646972, rs2020918, REN rs1464816, and rs5707) was performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and associations of the polymorphisms with RPL were evaluated by statistical analysis. The polymorphism PAI-1 rs1050955 GA+AA was associated with decreased RPL risk (AOR, 0.528; 95% CI 0.356–0.781; p = 0.001) as was the REN 10795 rs5707 GG genotype (AOR, 0.487; 95% CI 0.301–0.787; p = 0.003). In contrast, the tPA rs4646972 II genotype correlated with increased RPL risk (AOR, 1.606; 95% CI, 1.047–2.463; p = 0.030). This study provides evidence that tPA Alu rs4646972 may contribute to the risk of idiopathic RPL, but PAI-1 12068 rs1050955 and REN 10795 rs5707 are associated with a decreased risk of RPL. Therefore, these alleles may be useful as biomarkers to evaluate the risk of RPL. Full article
(This article belongs to the Section Omics/Informatics)
Article
The Influence of Baseline Clinical Status and Surgical Strategy on Early Good to Excellent Result in Spinal Lumbar Arthrodesis: A Machine Learning Approach
J. Pers. Med. 2021, 11(12), 1377; https://doi.org/10.3390/jpm11121377 - 16 Dec 2021
Cited by 3 | Viewed by 802
Abstract
The study aims to create a preoperative model from baseline demographic and health-related quality of life scores (HRQOL) to predict a good to excellent early clinical outcome using a machine learning (ML) approach. A single spine surgery center retrospective review of prospectively collected [...] Read more.
The study aims to create a preoperative model from baseline demographic and health-related quality of life scores (HRQOL) to predict a good to excellent early clinical outcome using a machine learning (ML) approach. A single spine surgery center retrospective review of prospectively collected data from January 2016 to December 2020 from the institutional registry (SpineREG) was performed. The inclusion criteria were age ≥ 18 years, both sexes, lumbar arthrodesis procedure, a complete follow up assessment (Oswestry Disability Index—ODI, SF-36 and COMI back) and the capability to read and understand the Italian language. A delta of improvement of the ODI higher than 12.7/100 was considered a “good early outcome”. A combined target model of ODI (Δ ≥ 12.7/100), SF-36 PCS (Δ ≥ 6/100) and COMI back (Δ ≥ 2.2/10) was considered an “excellent early outcome”. The performance of the ML models was evaluated in terms of sensitivity, i.e., True Positive Rate (TPR), specificity, i.e., True Negative Rate (TNR), accuracy and area under the receiver operating characteristic curve (AUC ROC). A total of 1243 patients were included in this study. The model for predicting ODI at 6 months’ follow up showed a good balance between sensitivity (74.3%) and specificity (79.4%), while providing a good accuracy (75.8%) with ROC AUC = 0.842. The combined target model showed a sensitivity of 74.2% and specificity of 71.8%, with an accuracy of 72.8%, and an ROC AUC = 0.808. The results of our study suggest that a machine learning approach showed high performance in predicting early good to excellent clinical results. Full article
(This article belongs to the Section Clinical Medicine, Cell, and Organism Physiology)
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Article
Prediction of Real-World Long-Term Outcomes of People with CF Homozygous for the F508del Mutation Treated with CFTR Modulators
J. Pers. Med. 2021, 11(12), 1376; https://doi.org/10.3390/jpm11121376 - 16 Dec 2021
Viewed by 888
Abstract
The clinical response to cystic fibrosis transmembrane conductance regulator (CFTR) modulators is variable within people with cystic fibrosis (pwCF) homozygous for the F508del mutation. The prediction of clinical effect in individual patients would be useful to target therapy to those who would benefit [...] Read more.
The clinical response to cystic fibrosis transmembrane conductance regulator (CFTR) modulators is variable within people with cystic fibrosis (pwCF) homozygous for the F508del mutation. The prediction of clinical effect in individual patients would be useful to target therapy to those who would benefit from it. A multicenter observational cohort study was conducted including 97 pwCF (F508del/F508del), who started lumacaftor/ivacaftor (LUM/IVA) treatment before June 2018. In order to assess the associations of individual in vivo and in vitro biomarkers with clinical outcomes, we collected clinical data regarding sex, age, and sweat chloride concentration (SwCl) at baseline and after six months of LUM/IVA; the percent predicted forced expiratory volume in 1 s (ppFEV1) and the number of pulmonary exacerbations (PEx) during the three years before up to three years after modulator initiation; and the forskolin-induced swelling (FIS) responses to LUM/IVA, quantified in intestinal organoids. On a group level, the results showed an acute change in ppFEV1 after LUM/IVA initiation (2.34%, 95% CI 0.85–3.82, p = 0.003), but no significant change in annual ppFEV1 decline in the three years after LUM/IVA compared to the three years before (change: 0.11% per year, 95%CI: −1.94–2.19, p = 0.913). Neither of these two outcomes was associated with any of the candidate predictors on an individual level. The median number of pulmonary exacerbations (PEx) per patient year did not significantly change in the three years after LUM/IVA compared to the years before (median: 0.33/patient year, IQR: 0–0.67 before vs. median: 0/patient year, IQR: 0–0.67 after p = 0. 268). The PEx rate after modulator initiation was associated with the PEx rate before (IRR: 2.26, 95%CI: 1.67–3.08, p < 0.001), with sex (males vs. females IRR: 0.36, 95%CI: 0.21–0.63, p = 0.001) and with sweat chloride concentration (SwCl) at baseline (IRR: 0.96, 95%CI: 0.94–0.98, p = 0.001). The change in SwCl was also significant (−22.9 mmol/L (95%CI: −27.1–−18.8, p < 0.001) and was associated with SwCl at baseline (−0.64, 95%CI: −0.90–−0.37, p < 0.001) and with sex (males vs. females 8.32, 95%CI: 1.82–14.82, p = 0.013). In conclusion, ppFEV1 decline after CFTR modulator initiation remains difficult to predict in individual patients in a real-world setting, with limited effectiveness for double CFTR modulator therapies. The PEx rate prior to CFTR modulator treatment initiation, sex and SwCl at baseline could be potential predictors of long-term PEx rate and of changes in SwCl after modulator initiation. Full article
(This article belongs to the Special Issue Cystic Fibrosis and Personalized Medicine)
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Review
Vertical Root Fracture in Non-Endodontically and Endodontically Treated Teeth: Current Understanding and Future Challenge
J. Pers. Med. 2021, 11(12), 1375; https://doi.org/10.3390/jpm11121375 - 16 Dec 2021
Cited by 5 | Viewed by 1229
Abstract
A vertical root fracture (VRF) is a complex complication that usually leads to tooth extraction. The aim of this article is to review the prevalence, demography, distribution, diagnostic methods, etiology and predisposing factors, clinical features, radiographic characteristics and treatment strategies of VRFs in [...] Read more.
A vertical root fracture (VRF) is a complex complication that usually leads to tooth extraction. The aim of this article is to review the prevalence, demography, distribution, diagnostic methods, etiology and predisposing factors, clinical features, radiographic characteristics and treatment strategies of VRFs in non-endodontically treated teeth (VRFNETT) and endodontically treated teeth (VRFETT). Search terms for each subject related to VRFNETT and VRFETT were entered into MEDLINE, PubMed and Google Scholar. Systematic reviews, retrospective cohort studies, demographic research, clinical studies, case reports and case series were reviewed. Most of the VRFs were found in patients older than 40 years old. Older populations were discovered in the non-endodontically treated VRF group when compared to the endodontically treated VRF group. Male patients were found at a greater prevalence than females in the non-endodontically treated VRF group. The initial occurrence of a VRF may accompany radiolucent lines within the root canal, unusual space between the canal wall and intracanal material, a widening of the PDL space along the periradicular surfaces, angular bony destruction, step-like bone defects, V-shaped diffuse bone defects, or root resorptions corresponding to the fracture line before the clear separation of the fractured fragment. The indicative clinical and radiographic signs of VRF included a coronally positioned sinus tract, deep-narrow periodontal defects, the displacement of a fractured fragment, periradicular radiolucent halos and the widening of the root canal space. Interestingly, VRFNETT are more often observed in the Chinese population. Some patients with multiple VRFs were observed, suggesting possible predisposing factors in genetics and tooth development. The management of a VRF usually involves a multidisciplinary approach. The common distribution and features of VRFNETT and VRFETT were elucidated to facilitate recognition and diagnosis. Besides extraction, variable therapeutic schemes, such as the repair of the VRF, root amputation and others reported in earlier literature, are available. A long-term prognosis study of the various therapeutic strategies is needed. Full article
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Review
Unraveling the Relationship of Asthma and COVID-19
J. Pers. Med. 2021, 11(12), 1374; https://doi.org/10.3390/jpm11121374 - 16 Dec 2021
Viewed by 918
Abstract
Viral infections are one of the main causes of asthma exacerbations. During the COVID-19 era, concerns regarding the relationship of SARS-CoV2 with asthma have been raised. The concerns are both for COVID severity and asthma exacerbations. Many studies on COVID-19 epidemiology and comorbidities [...] Read more.
Viral infections are one of the main causes of asthma exacerbations. During the COVID-19 era, concerns regarding the relationship of SARS-CoV2 with asthma have been raised. The concerns are both for COVID severity and asthma exacerbations. Many studies on COVID-19 epidemiology and comorbidities have assessed whether asthma represents a risk factor for SARS-CoV2 infection and/or more severe course of the disease. This review covers the current evidence on the prevalence of asthma in COVID-19 and its association with susceptibility to and severity of SARS-CoV2 infection. It will examine the possible role of underlying asthma severity in COVID-19 related outcomes as well as the molecular mechanisms involved in the co-existence of these entities. The possible role of asthma inflammatory phenotypes will also be evaluated. Finally, the impact of asthma comorbidities and the implications of asthma medication on COVID-19 will be addressed. Full article
(This article belongs to the Special Issue Asthma: From Phenotypes to Personalized Medicine)
Review
The Potential of Hsp90 in Targeting Pathological Pathways in Cardiac Diseases
J. Pers. Med. 2021, 11(12), 1373; https://doi.org/10.3390/jpm11121373 - 16 Dec 2021
Viewed by 1722
Abstract
Heat shock protein 90 (Hsp90) is a molecular chaperone that interacts with up to 10% of the proteome. The extensive involvement in protein folding and regulation of protein stability within cells makes Hsp90 an attractive therapeutic target to correct multiple dysfunctions. Many of [...] Read more.
Heat shock protein 90 (Hsp90) is a molecular chaperone that interacts with up to 10% of the proteome. The extensive involvement in protein folding and regulation of protein stability within cells makes Hsp90 an attractive therapeutic target to correct multiple dysfunctions. Many of the clients of Hsp90 are found in pathways known to be pathogenic in the heart, ranging from transforming growth factor β (TGF-β) and mitogen activated kinase (MAPK) signaling to tumor necrosis factor α (TNFα), Gs and Gq g-protein coupled receptor (GPCR) and calcium (Ca2+) signaling. These pathways can therefore be targeted through modulation of Hsp90 activity. The activity of Hsp90 can be targeted through small-molecule inhibition. Small-molecule inhibitors of Hsp90 have been found to be cardiotoxic in some cases however. In this regard, specific targeting of Hsp90 by modulation of post-translational modifications (PTMs) emerges as an attractive strategy. In this review, we aim to address how Hsp90 functions, where Hsp90 interacts within pathological pathways, and current knowledge of small molecules and PTMs known to modulate Hsp90 activity and their potential as therapeutics in cardiac diseases. Full article
(This article belongs to the Special Issue Therapeutic Targets and Personalized Medicine in Cardiac Disease)
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Article
Predictive Model for High Coronary Artery Calcium Score in Young Patients with Non-Dialysis Chronic Kidney Disease
J. Pers. Med. 2021, 11(12), 1372; https://doi.org/10.3390/jpm11121372 - 15 Dec 2021
Cited by 2 | Viewed by 806
Abstract
Cardiovascular disease is a major complication of chronic kidney disease. The coronary artery calcium (CAC) score is a surrogate marker for the risk of coronary artery disease. The purpose of this study is to predict outcomes for non-dialysis chronic kidney disease patients under [...] Read more.
Cardiovascular disease is a major complication of chronic kidney disease. The coronary artery calcium (CAC) score is a surrogate marker for the risk of coronary artery disease. The purpose of this study is to predict outcomes for non-dialysis chronic kidney disease patients under the age of 60 with high CAC scores using machine learning techniques. We developed the predictive models with a chronic kidney disease representative cohort, the Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease (KNOW-CKD). We divided the cohort into a training dataset (70%) and a validation dataset (30%). The test dataset incorporated an external dataset of patients that were not included in the KNOW-CKD cohort. Support vector machine, random forest, XGboost, logistic regression, and multi-perceptron neural network models were used in the predictive models. We evaluated the model’s performance using the area under the receiver operating characteristic (AUROC) curve. Shapley additive explanation values were applied to select the important features. The random forest model showed the best predictive performance (AUROC 0.87) and there was a statistically significant difference between the traditional logistic regression model and the test dataset. This study will help identify patients at high risk of cardiovascular complications in young chronic kidney disease and establish individualized treatment strategies. Full article
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Article
Cardiac Remodeling According to the Nocturnal Fall of Blood Pressure in Hypertensive Subjects: The Whole Assessment of Cardiac Abnormalities in Non-Dipper Subjects with Arterial Hypertension (Wacanda) Study
J. Pers. Med. 2021, 11(12), 1371; https://doi.org/10.3390/jpm11121371 - 15 Dec 2021
Cited by 1 | Viewed by 758
Abstract
Objective: Several epidemiological studies suggest that the preservation of the physiological circadian rhythm of blood pressure or its disruption affects the extent of the organ damage developed by the patient. If we classify the circadian rhythm of blood pressure into four nocturnal profiles, [...] Read more.
Objective: Several epidemiological studies suggest that the preservation of the physiological circadian rhythm of blood pressure or its disruption affects the extent of the organ damage developed by the patient. If we classify the circadian rhythm of blood pressure into four nocturnal profiles, significant differences emerge in terms of organ damage burden and prognosis: reverse dippers have the worst prognosis while dippers and mild dippers fall into an intermediate risk range. The risk profile of extreme dippers is still debated, and the available data are very conflicting and inconclusive. Starting from this gap of knowledge, we aimed to evaluate, retrospectively, in a cohort of hypertensive subjects, the degree of cardiac involvement in relation to the different nocturnal blood pressure profiles. Methods: We retrospectively evaluated 900 patients with essential hypertension, of whom 510 met our study criteria. We graded the 510 patients in relation to the percentage of reduction in mean systolic blood pressure (SBP) at night-time compared with day-time, considering this as a continuous variable, and then compared the extreme quintiles with each other and with the middle quintile (considered as reference). Results: Patients with less (or no) reduction in nocturnal SBP (reverse dipper) showed a higher level of organ damage and comorbidities. With regard to echocardiographic indexes, patients with maximum nocturnal pressure reduction (extreme dipper) showed a lower level of remodeling and/or impairment of E/e’ ratio, Right Atrium Area, Basal Right Ventricular Diameter, Inferior Vena Cava Average Diameter, and Tricuspidal Anular Plane Systolic Excursion compared also with hypertensive patients with a physiological nocturnal pressure reduction, even after correction for the main confounders. Conclusions: These data suggest that extreme dippers may constitute the subgroup of hypertensive patients with the lowest 24-h pressure load and, therefore, less cardiac remodeling. Full article
(This article belongs to the Special Issue Cardiac Disease: Diagnosis, Treatment, and Outcomes)
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Review
MET Gene Dysregulation as a Promising Therapeutic Target in Lung Cancer—A Review
J. Pers. Med. 2021, 11(12), 1370; https://doi.org/10.3390/jpm11121370 - 14 Dec 2021
Cited by 1 | Viewed by 1117
Abstract
Several molecular abnormalities in the MET gene have been identified, including overexpression, amplification, point mutations, and “skipping mutation” in exon 14. Even though deregulated MET signaling occurs rarely in non-small cell lung cancer (NSCLC), it possesses tumorigenic activity. Since the discovery of the [...] Read more.
Several molecular abnormalities in the MET gene have been identified, including overexpression, amplification, point mutations, and “skipping mutation” in exon 14. Even though deregulated MET signaling occurs rarely in non-small cell lung cancer (NSCLC), it possesses tumorigenic activity. Since the discovery of the significant role played by MET dysregulations in resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI), many clinical trials have been focused on mechanisms underlying this acquired resistance. Therefore, new therapeutic strategies are being considered in the personalized therapy of NSCLC patients carrying MET abnormalities. First, MET kinase inhibitors (tepotinib and capmatinib) have been shown to be effective in the first and subsequent lines of treatment in NSCLC patients with “skipping mutations” in exon 14 of MET gene. In this article, the authors show the role of MET signaling pathway alterations and describe the results of clinical trials with MET inhibitors in NSCLC patients. Full article
(This article belongs to the Section Methodology, Drug and Device Discovery)
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Article
Physical Exercise with or without Whole-Body Vibration in Breast Cancer Patients Suffering from Aromatase Inhibitor—Induced Musculoskeletal Symptoms: A Pilot Randomized Clinical Study
J. Pers. Med. 2021, 11(12), 1369; https://doi.org/10.3390/jpm11121369 - 14 Dec 2021
Cited by 3 | Viewed by 1099
Abstract
In this study, we aimed to assess the safety and efficacy of physical exercise, with or without whole-body vibration (WBV), in patients with aromatase inhibitor-induced musculoskeletal symptoms (AIMSS). Eligible patients were adults (≥18 years) with a history of breast cancer and current AIMSS. [...] Read more.
In this study, we aimed to assess the safety and efficacy of physical exercise, with or without whole-body vibration (WBV), in patients with aromatase inhibitor-induced musculoskeletal symptoms (AIMSS). Eligible patients were adults (≥18 years) with a history of breast cancer and current AIMSS. Enrolled patients (n = 22) were randomly assigned 1:1 to receive physical exercise combined with WBV or sham WBV for 4 weeks. The primary endpoint was pain intensity measured by numerical pain rating scale (NPRS). The secondary endpoints were muscle strength, physical function, physical performance, and quality of life. The WBV group (mean age: 51.73 ± 10.73 years; body mass index (BMI): 25.56 ± 5.17 kg/m2) showed a statistically significant pain reduction (NPRS: 6.82 ± 1.17 vs. 5.73 ± 1.01; p = 0.031), whereas patients in the sham WBV group (mean age: 58.55 ± 9.71 years; BMI: 27.31 ± 3.84 kg/m2), did not reach statistical significance (NPRS: 6.91 ± 2.02 vs. 5.91 ± 2.51; p = 0.07). Concurrently, muscle strength, physical performance, and quality of life significantly improved in both groups, without significant differences between groups. No dropouts and no side effects were recorded. Both patients and the physical therapist reported a high level of satisfaction with the intervention. Our findings suggest that physical exercise and WBV combination might be a safe therapeutic option for improving the rehabilitative management of patients with AIMSS. Full article
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Article
What Influences Women to Adhere to Pelvic Floor Exercises after Physiotherapy Treatment? A Qualitative Study for Individualized Pelvic Health Care
J. Pers. Med. 2021, 11(12), 1368; https://doi.org/10.3390/jpm11121368 - 14 Dec 2021
Cited by 3 | Viewed by 1101
Abstract
Conservative treatment of pelvic floor dysfunction (PFD) includes therapeutic exercise for pelvic floor muscle (PFM) training or other complementary exercise modalities, such as hypopressive exercises. However, the long-term effectiveness of the conservative treatment depends on a patient’s adherence to the exercises and the [...] Read more.
Conservative treatment of pelvic floor dysfunction (PFD) includes therapeutic exercise for pelvic floor muscle (PFM) training or other complementary exercise modalities, such as hypopressive exercises. However, the long-term effectiveness of the conservative treatment depends on a patient’s adherence to the exercises and the integration of professional health advice into their daily life. The objective of this study was to establish the adherence experience of women with diagnosed PFD in home-based exercises after an intensive face-to-face physiotherapy treatment. A qualitative study from an interpretive paradigm was developed. Semi-structured individual and group interviews were performed 6 months after finishing individual physiotherapy treatment. The interviews were recorded, fully transcribed and analyzed thematically by creating categories. Thirty-one women were interviewed. The women reported that their adherence to home PFM exercises depended on the exercise program itself, its efficacy, their personal experiences with the exercises, intrinsic factors such as self-awareness or beliefs, and extrinsic factors, such as professional or instrumental feedback. Thus, therapeutic adherence could be more likely with effective physiotherapy programs that include mutually agreed home exercises and simple movements women can build into their daily lives. Improving awareness and knowledge of the pelvic region and the importance of PFM treatment as well as consideration for potential worsening of PFD will also encourage women to adhere to the exercises. Full article
(This article belongs to the Special Issue Personalized Nursing and Health Care)
Article
Chronic Kidney Disease and Its Relationship with Mental Health: Allostatic Load Perspective for Integrated Care
J. Pers. Med. 2021, 11(12), 1367; https://doi.org/10.3390/jpm11121367 - 14 Dec 2021
Cited by 2 | Viewed by 1079
Abstract
Background: Chronic renal failure is a chronic medical condition characterized by a progressive and irreversible loss of kidney function. Up to 50% of patients undergoing dialysis experience symptoms of depression and anxiety: what is the impact of individual factors and medical conditions on [...] Read more.
Background: Chronic renal failure is a chronic medical condition characterized by a progressive and irreversible loss of kidney function. Up to 50% of patients undergoing dialysis experience symptoms of depression and anxiety: what is the impact of individual factors and medical conditions on the mental health issue? The present study was carried out to investigate the individual factors (biomarkers and psychological dimensions) of end-stage renal disease patients dealing with dialysis, analyzing their predictor values for developing negative disease adaptations by an allostatic paradigm. Methods: We conducted an observational study on 35 patients affected by end-stage renal disease; biological and psychological markers have been detected. We conducted descriptive statistical analyses (t-tests) and performed a hierarchical regression analysis to investigate the relationship between pathological medical conditions and psychological dimensions. Results: The findings showed a positive correlation between creatinine levels and psychological distress as well as stress index. No significant effect of “time of dialysis”, “time from diagnosis”, “age” and “personality traits” was found. Conclusion: Our findings showed that personality traits did not represent a protective factor by moderating positive emotional adaptations; conversely, creatinine levels appeared predictive for negative emotional adaptations. High levels of creatinine were found to be positively associated with high stress levels as well psychological distress. According to the allostatic paradigm, end-stage renal disease patients could experience an allostatic load and more overload towards poor health outcomes; integrated biological and psychological measurements could prevent increased negative mental health through a patient-centered approach. Full article
(This article belongs to the Special Issue Frontiers in Chronic Kidney Disease)
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Article
Lifestyle Variables Such as Daily Internet Use, as Promising Protective Factors against Cognitive Impairment in Patients with Subjective Memory Complaints. Preliminary Results
J. Pers. Med. 2021, 11(12), 1366; https://doi.org/10.3390/jpm11121366 - 14 Dec 2021
Cited by 1 | Viewed by 1087
Abstract
Subjective memory complaints (SMCs) may be important markers in the prediction of cognitive deterioration. The aim of this study was to find associations between individual lifestyle factors, which may contribute to cognitive impairment (CI) in people with SMCs and to conduct a literature [...] Read more.
Subjective memory complaints (SMCs) may be important markers in the prediction of cognitive deterioration. The aim of this study was to find associations between individual lifestyle factors, which may contribute to cognitive impairment (CI) in people with SMCs and to conduct a literature review on the relationship between internet use and CI in subjects over 50 years old, as a related factor. This was a case-controlled study that included 497 subjects aged over 50 years with SMCs who were recruited from 19 community pharmacies. Three screening tests were used to detect possible CIs, and individuals with at least one test result compatible with a CI were referred to primary care for evaluation. Having self-referred SMC increased the odds of obtaining scores compatible with CI and this factor was significantly related to having feelings of depression (OR = 2.24, 95% CI [1.34, 3.90]), taking anxiolytics or antidepressants (OR = 1.93, 95% CI [1.23, 3.05]), and being female (OR = 1.83, 95% CI [1.15, 2.88]). Thirty percent of our sample obtained scores compatible with CI. Age over 70 years increased the odds of obtaining scores compatible with CI. A high-level education, reading, and daily internet use were factors associated with a reduced risk of positive scores compatible with CI (37–91%, 7–18%, and 67–86%, respectively), while one extra hour television per day increased the risk by 8–30%. Among others, modifiable lifestyle factors such as reading, and daily internet usage may slow down cognitive decline in patients over 50 with SMCs. Four longitudinal studies and one quasi-experimental study found internet use to be beneficial against CI in patients over 50 years of age. Full article
(This article belongs to the Section Epidemiology)
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Editorial
Ocular Vascular Changes: Choroidal Thickness as an Early Biomarker for Alzheimer’s Disease?
J. Pers. Med. 2021, 11(12), 1365; https://doi.org/10.3390/jpm11121365 - 14 Dec 2021
Viewed by 742
Abstract
Alzheimer’s disease (AD) is an age-related neurodegenerative and progressive disorder representing the most common form of dementia among the elderly [...] Full article
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Review
Making More Womb: Clinical Perspectives Supporting the Development and Utilization of Mesenchymal Stem Cell Therapy for Endometrial Regeneration and Infertility
J. Pers. Med. 2021, 11(12), 1364; https://doi.org/10.3390/jpm11121364 - 14 Dec 2021
Cited by 4 | Viewed by 1360
Abstract
The uterus is a homeostatic organ, unwavering in the setting of monthly endometrial turnover, placental invasion, and parturition. In response to ovarian steroid hormones, the endometrium autologously prepares for embryo implantation and in its absence will shed and regenerate. Dysfunctional endometrial repair and [...] Read more.
The uterus is a homeostatic organ, unwavering in the setting of monthly endometrial turnover, placental invasion, and parturition. In response to ovarian steroid hormones, the endometrium autologously prepares for embryo implantation and in its absence will shed and regenerate. Dysfunctional endometrial repair and regeneration may present clinically with infertility and abnormal menses. Asherman’s syndrome is characterized by intrauterine adhesions and atrophic endometrium, which often impacts fertility. Clinical management of infertility associated with abnormal endometrium represents a significant challenge. Endometrial mesenchymal stem cells (MSC) occupy a perivascular niche and contain regenerative and immunomodulatory properties. Given these characteristics, mesenchymal stem cells of endometrial and non-endometrial origin (bone marrow, adipose, placental) have been investigated for therapeutic purposes. Local administration of human MSC in animal models of endometrial injury reduces collagen deposition, improves angiogenesis, decreases inflammation, and improves fertility. Small clinical studies of autologous MSC administration in infertile women with Asherman’s Syndrome suggested their potential to restore endometrial function as evidenced by increased endometrial thickness, decreased adhesions, and fertility. The objective of this review is to highlight translational and clinical studies investigating the use of MSC for endometrial dysfunction and infertility and to summarize the current state of the art in this promising area. Full article
(This article belongs to the Special Issue Endometrial Stem/Progenitor Cell Biology: Prospects and Challenges)
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Review
The Impact of Primary Tumor Location on Long-Term Oncological Outcomes in Patients with Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy: A Systematic Review and Meta-Analysis
J. Pers. Med. 2021, 11(12), 1363; https://doi.org/10.3390/jpm11121363 - 14 Dec 2021
Cited by 1 | Viewed by 1009
Abstract
Background: Upper tract urothelial carcinoma (UTUC) accounts for up to 10% of all urothelial neoplasms. Currently, various tumor-related factors are proposed to be of importance in UTUC prognostic models; however, the association of the primary UTUC location with oncological outcomes remains controversial. Thus, [...] Read more.
Background: Upper tract urothelial carcinoma (UTUC) accounts for up to 10% of all urothelial neoplasms. Currently, various tumor-related factors are proposed to be of importance in UTUC prognostic models; however, the association of the primary UTUC location with oncological outcomes remains controversial. Thus, we sought to perform a systematic review and meta-analysis of the latest available evidence and assess the impact of primary tumor location on long-term oncological outcomes in patients with UTUC undergoing radical nephroureterectomy. Materials and Methods: A computerized systematic literature search was conducted in October 2021 through the PubMed, Web of Science, Scopus, and Cochrane Library databases. The primary endpoint was cancer-specific survival (CSS), and the secondary endpoints were overall survival (OS) and disease-free survival (DFS). Effect measures for the analyzed outcomes were reported hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Among the total number of 16,836 UTUC in 17 included studies, 10,537 (62.6%) were renal pelvic tumors (RPTs), and 6299 (37.4%) were ureteral tumors (UTs). Pooled results indicated that patients with UT had significantly worse CSS (HR: 1.37, p < 0.001), OS (HR: 1.26, p = 0.003, and DFS (HR: 1.51, p < 0.001) compared to patients with RPT. Based on performed subgroup analyses, we identified different definitions of primary tumor location and geographical region as potential sources of heterogeneity. Conclusions: Ureteral location of UTUC is associated with significantly worse long-term oncological outcomes. Our results support the need for close follow-up and the consideration of perioperative chemotherapy in patients with UTUC located in the ureter. However, further prospective studies are needed to draw final conclusions. Full article
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Editorial
The Journey of an Outstanding Scientific Mind: Prof Hiroshi Maeda (1938–2021)
J. Pers. Med. 2021, 11(12), 1362; https://doi.org/10.3390/jpm11121362 - 14 Dec 2021
Viewed by 725
Abstract
In the mid-70s of the last century, Prof [...] Full article
Review
Kinesin Family Member C1 (KIFC1/HSET): A Potential Actionable Biomarker of Early Stage Breast Tumorigenesis and Progression of High-Risk Lesions
J. Pers. Med. 2021, 11(12), 1361; https://doi.org/10.3390/jpm11121361 - 14 Dec 2021
Cited by 1 | Viewed by 970
Abstract
The enigma of why some premalignant or pre-invasive breast lesions transform and progress while others do not remains poorly understood. Currently, no radiologic or molecular biomarkers exist in the clinic that can successfully risk-stratify high-risk lesions for malignant transformation or tumor progression as [...] Read more.
The enigma of why some premalignant or pre-invasive breast lesions transform and progress while others do not remains poorly understood. Currently, no radiologic or molecular biomarkers exist in the clinic that can successfully risk-stratify high-risk lesions for malignant transformation or tumor progression as well as serve as a minimally cytotoxic actionable target for at-risk subpopulations. Breast carcinogenesis involves a series of key molecular deregulatory events that prompt normal cells to bypass tumor-suppressive senescence barriers. Kinesin family member C1 (KIFC1/HSET), which confers survival of cancer cells burdened with extra centrosomes, has been observed in premalignant and pre-invasive lesions, and its expression has been shown to correlate with increasing neoplastic progression. Additionally, KIFC1 has been associated with aggressive breast tumor molecular subtypes, such as basal-like and triple-negative breast cancers. However, the role of KIFC1 in malignant transformation and its potential as a predictive biomarker of neoplastic progression remain elusive. Herein, we review compelling evidence suggesting the involvement of KIFC1 in enabling pre-neoplastic cells to bypass senescence barriers necessary to become immortalized and malignant. We also discuss evidence inferring that KIFC1 levels may be higher in premalignant lesions with a greater inclination to transform and acquire aggressive tumor intrinsic subtypes. Collectively, this evidence provides a strong impetus for further investigation into KIFC1 as a potential risk-stratifying biomarker and minimally cytotoxic actionable target for high-risk patient subpopulations. Full article
(This article belongs to the Special Issue Personalized Treatment Strategy in Early Breast Cancer)
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Article
A Low-Protein Diet with a Renal-Specific Oral Nutrition Supplement Helps Maintain Nutritional Status in Patients with Advanced Chronic Kidney Disease
J. Pers. Med. 2021, 11(12), 1360; https://doi.org/10.3390/jpm11121360 - 14 Dec 2021
Cited by 1 | Viewed by 1153
Abstract
A low-protein diet (LPD) is recommended to patients with non-dialysis advanced chronic kidney disease (CKD) for delaying renal function decline. However, this approach potentially prevents an adequate calorie and micronutrient intake. We examined the influence of an LPD including a renal-specific oral nutrition [...] Read more.
A low-protein diet (LPD) is recommended to patients with non-dialysis advanced chronic kidney disease (CKD) for delaying renal function decline. However, this approach potentially prevents an adequate calorie and micronutrient intake. We examined the influence of an LPD including a renal-specific oral nutrition supplement (RONS) on the nutrition status of patients with stage 3b–5 CKD. This multicenter, open-label study prospectively enrolled patients over 18 years of age, with an estimated glomerular filtration rate (eGFR) between 10 and 45 mL/min/1.73 m2, serum albumin ≥3.0 g/dL, and body mass index ≤30 kg/m2. All participants implemented the LPD with one serving of RONS daily for 6 months. Daily energy intake, nutrition status, renal function, and quality of life were assessed before and after the intervention. Of 53 enrolled patients, 35 (66.0%) completed the study. We found that RONS use increased patients’ energy intake and maintained their serum albumin, nutritional status, and quality of life. Body weight and handgrip strength increased significantly at 6 months after enrollment (p = 0.0357); eGFR slightly decreased at 3 and 6 months after enrollment, suggesting that patients’ residual renal function was preserved. Our findings support the conclusion that patients with non-dialysis advanced CKD may benefit from additional RONS besides their regular diet. Patients with advanced CKD receiving RONS might achieve better nutrition and delay renal function decline. Full article
(This article belongs to the Special Issue Precision Prevention and Care in Chronic Kidney Disease)
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Article
Outcome of Critically Ill COVID-19 Patients According to the Setting of Corticosteroid Initiation—A Retrospective Observational Cohort Study
J. Pers. Med. 2021, 11(12), 1359; https://doi.org/10.3390/jpm11121359 - 13 Dec 2021
Viewed by 774
Abstract
(1) Background: Corticosteroids lower 28-day all-cause mortality in critically ill COVID-19 patients. However, the outcome of COVID-19 patients referred to the intensive care unit (ICU) for respiratory deterioration despite corticosteroids initiated during hospitalization before ICU admission has been poorly investigated. Our objective was [...] Read more.
(1) Background: Corticosteroids lower 28-day all-cause mortality in critically ill COVID-19 patients. However, the outcome of COVID-19 patients referred to the intensive care unit (ICU) for respiratory deterioration despite corticosteroids initiated during hospitalization before ICU admission has been poorly investigated. Our objective was to determine survival according to corticosteroid initiation setting. (2) Methods: We conducted a cohort study including all successive critically ill COVID-19 patients treated with corticosteroids and managed in our ICU. We compared survival, whether corticosteroids were initiated before (Cb-group) or after ICU admission (Ca-group), using a propensity score matching. (3) Results: Overall, 228 patients (67 years (56–74); 168M/60F; invasive mechanical ventilation on admission, 17%) were included with 63 patients in the Cb-group and 165 patients in the Ca-group. Survival to hospital discharge was 43% versus 69%, respectively (p = 0.001). In a multivariable analysis, factors associated with death were age (odds ratio, 1.07; 95%-confidence interval, (1.04–1.11); p < 0.0001), the sequential organ failure assessment (SOFA) score on ICU admission (1.30 (1.14–1.50); p = 0.0001) and corticosteroid initiation before ICU admission (2.64 (1.30–5.43); p = 0.007). No significant differences in outcome related to corticosteroid regimen were found. (4) Conclusions: Critically ill COVID-19 patients transferred to the ICU with deterioration despite corticosteroids initiated before admission have a less favorable outcome than patients receiving corticosteroids initiated after ICU admission. Full article
(This article belongs to the Special Issue Recent Advances on Coronavirus Disease 2019 (COVID-19))
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