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Volume 10
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J. Pers. Med., Volume 10, Issue 4 (December 2020) – 154 articles

Cover Story (view full-size image): The data from digitized social interactions can take us beyond the limits of the naked eye and help us capture the autistic capacity for social readiness. Using personalized analytics, we can track the person’s dynamics with biosensors that continuously co-register the micro-movements derived from their biorhythms. More important yet, we can track the spontaneously self-emerging cohesiveness of their social rapport and better inform our decisions on whether and when the socio-motor patterns of autistic people unexpectedly match those of neurotypical controls performing the same social task. Our new unifying statistical methods help us bridge the enormous social gap that current diagnostics, missing this information, have created between autistic and neurotypical people. View this paper
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23 pages, 1932 KiB  
Review
Metabolomics for Diagnosis and Prognosis of Uterine Diseases? A Systematic Review
by Janina Tokarz, Jerzy Adamski and Tea Lanišnik Rižner
J. Pers. Med. 2020, 10(4), 294; https://doi.org/10.3390/jpm10040294 - 21 Dec 2020
Cited by 19 | Viewed by 4503
Abstract
This systematic review analyses the contribution of metabolomics to the identification of diagnostic and prognostic biomarkers for uterine diseases. These diseases are diagnosed invasively, which entails delayed treatment and a worse clinical outcome. New options for diagnosis and prognosis are needed. PubMed, OVID, [...] Read more.
This systematic review analyses the contribution of metabolomics to the identification of diagnostic and prognostic biomarkers for uterine diseases. These diseases are diagnosed invasively, which entails delayed treatment and a worse clinical outcome. New options for diagnosis and prognosis are needed. PubMed, OVID, and Scopus were searched for research papers on metabolomics in physiological fluids and tissues from patients with uterine diseases. The search identified 484 records. Based on inclusion and exclusion criteria, 44 studies were included into the review. Relevant data were extracted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) checklist and quality was assessed using the QUADOMICS tool. The selected metabolomics studies analysed plasma, serum, urine, peritoneal, endometrial, and cervico-vaginal fluid, ectopic/eutopic endometrium, and cervical tissue. In endometriosis, diagnostic models discriminated patients from healthy and infertile controls. In cervical cancer, diagnostic algorithms discriminated patients from controls, patients with good/bad prognosis, and with/without response to chemotherapy. In endometrial cancer, several models stratified patients from controls and recurrent from non-recurrent patients. Metabolomics is valuable for constructing diagnostic models. However, the majority of studies were in the discovery phase and require additional research to select reliable biomarkers for validation and translation into clinical practice. This review identifies bottlenecks that currently prevent the translation of these findings into clinical practice. Full article
(This article belongs to the Special Issue Personalized Medicine in Women's Cancer)
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13 pages, 982 KiB  
Article
Practical Barriers and Facilitators Experienced by Patients, Pharmacists and Physicians to the Implementation of Pharmacogenomic Screening in Dutch Outpatient Hospital Care—An Explorative Pilot Study
by Pauline Lanting, Evelien Drenth, Ludolf Boven, Amanda van Hoek, Annemiek Hijlkema, Ellen Poot, Gerben van der Vries, Robert Schoevers, Ernst Horwitz, Reinold Gans, Jos Kosterink, Mirjam Plantinga, Irene van Langen, Adelita Ranchor, Cisca Wijmenga, Lude Franke, Bob Wilffert and Rolf Sijmons
J. Pers. Med. 2020, 10(4), 293; https://doi.org/10.3390/jpm10040293 - 21 Dec 2020
Cited by 12 | Viewed by 4696
Abstract
Pharmacogenomics (PGx) can provide optimized treatment to individual patients while potentially reducing healthcare costs. However, widespread implementation remains absent. We performed a pilot study of PGx screening in Dutch outpatient hospital care to identify the barriers and facilitators to implementation experienced by patients [...] Read more.
Pharmacogenomics (PGx) can provide optimized treatment to individual patients while potentially reducing healthcare costs. However, widespread implementation remains absent. We performed a pilot study of PGx screening in Dutch outpatient hospital care to identify the barriers and facilitators to implementation experienced by patients (n = 165), pharmacists (n = 58) and physicians (n = 21). Our results indeed suggest that the current practical experience of healthcare practitioners with PGx is limited, that proper education is necessary, that patients want to know the exact implications of the results, that healthcare practitioners heavily rely on their computer systems, that healthcare practitioners encounter practical problems in the systems used, and a new barrier was identified, namely that there is an unclear allocation of responsibilities between healthcare practitioners about who should discuss PGx with patients and apply PGx results in healthcare. We observed a positive attitude toward PGx among all the stakeholders in our study, and among patients, this was independent of the occurrence of drug-gene interactions during their treatment. Facilitators included the availability of and adherence to Dutch Pharmacogenetics Working Group guidelines. While clinical decision support (CDS) is available and valued in our medical center, the lack of availability of CDS may be an important barrier within Dutch healthcare in general. Full article
(This article belongs to the Special Issue Pharmacogenomics: From Basic Research to Clinical Implementation)
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15 pages, 1281 KiB  
Article
From Proteomics to Personalized Medicine: The Importance of Isoflavone Dose and Estrogen Receptor Status in Breast Cancer Cells
by Maria Ilieș, Alina Uifălean, Sergiu Pașca, Vishnu Mukund Dhople, Michael Lalk, Cristina Adela Iuga and Elke Hammer
J. Pers. Med. 2020, 10(4), 292; https://doi.org/10.3390/jpm10040292 - 19 Dec 2020
Cited by 7 | Viewed by 2913
Abstract
Continuing efforts are directed towards finding alternative breast cancer chemotherapeutics, with improved safety and efficacy profiles. Soy isoflavones represent promising agents but, despite extensive research, limited information exists regarding their impact on the breast cancer cell proteome. The purpose of this study was [...] Read more.
Continuing efforts are directed towards finding alternative breast cancer chemotherapeutics, with improved safety and efficacy profiles. Soy isoflavones represent promising agents but, despite extensive research, limited information exists regarding their impact on the breast cancer cell proteome. The purpose of this study was to compare the proteomic profiles of MCF-7 (estrogen responsive) and MDA-MB-231 (estrogen non-responsive) breast cancer cells exposed to different concentrations of genistein, daidzein, and a soy seed extract, using a high throughput LC–UDMSE protein profiling approach. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay confirmed the dual activity of soy isoflavones on MCF-7 cells and the inhibitory effect on MDA-MB-231 cells. Proteome profiling of paramagnetic beads prepared peptides by nano-LC UDMSE and pathway enrichment analysis revealed that isoflavones affected distinct molecular pathways in MCF-7 and MDA-MB-231 cells, such as tyrosine kinases signaling pathway, cytoskeleton organization, lipid and phospholipid catabolism, extracellular matrix degradation and mRNA splicing. Also, in MCF-7 cells, low and high isoflavone doses induced different changes of the proteome, including cell cycle alterations. Therefore, the expression of estrogen receptors and the isoflavone dose are determinant factors for the molecular impact of isoflavones and must be taken into account when considering adjuvant breast cancer therapy towards personalized medicine. Full article
(This article belongs to the Special Issue Proteomics and Personalized Medicine)
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11 pages, 614 KiB  
Article
Palbociclib Plus Fulvestrant or Everolimus Plus Exemestane for Pretreated Advanced Breast Cancer with Lobular Histotype in ER+/HER2− Patients: A Propensity Score-Matched Analysis of a Multicenter Retrospective Patient Series
by Armando Orlandi, Elena Iattoni, Laura Pizzuti, Agnese Fabbri, Andrea Botticelli, Carmela Di Dio, Antonella Palazzo, Giovanna Garufi, Giulia Indellicati, Daniele Alesini, Luisa Carbognin, Ida Paris, Angela Vaccaro, Luca Moscetti, Alessandra Fabi, Valentina Magri, Giuseppe Naso, Alessandra Cassano, Patrizia Vici, Diana Giannarelli, Gianluca Franceschini, Paolo Marchetti, Emilio Bria and Giampaolo Tortoraadd Show full author list remove Hide full author list
J. Pers. Med. 2020, 10(4), 291; https://doi.org/10.3390/jpm10040291 - 18 Dec 2020
Cited by 4 | Viewed by 2724
Abstract
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) show meaningful efficacy and tolerability in patients with metastatic breast cancer (MBC), but the optimal sequence of ET has not been established. It is not clear if patients with lobular breast carcinomas [...] Read more.
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) show meaningful efficacy and tolerability in patients with metastatic breast cancer (MBC), but the optimal sequence of ET has not been established. It is not clear if patients with lobular breast carcinomas (LBC) derive the same benefits when receiving second line CDK4/6i. This retrospective study compared the efficacy of palbociclib plus fulvestrant (PALBO–FUL) with everolimus plus exemestane (EVE–EXE) as second-line ET for hormone-resistant metastatic LBC. From 2013 to 2018, patients with metastatic LBC positivity for estrogen and/or progesterone receptors and HER2/neu negativity, who had relapsed during adjuvant hormonal therapy or first-line hormonal treatment, were enrolled from six centers in Italy in this retrospective study. A total of 74 out of 376 patients (48 treated with PALBO–FUL and 26 with EVE–EXE) with metastatic LBC were eligible for inclusion. Progression-free survival (PFS) was longer in patients receiving EVE–EXE compared with PALBO–FUL (6.1 vs. 4.5 months, univariate HR 0.58, 95% CI 0.35–0.96; p = 0.025). On the propensity score (PS) analysis, PFS was confirmed to be significantly longer for patients treated with EVE–EXE compared to PALBO–FUL (6.0 vs. 4.6 months, p = 0.04). This retrospective analysis suggests that EVE–EXE is more effective than PALBO–FUL for second line ET of metastatic LBC, allowing us to speculate on the optimal therapeutic sequence. Full article
(This article belongs to the Special Issue Innovations in the Integrated Management of Breast Cancer)
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17 pages, 2394 KiB  
Article
Cerebrospinal Fluid Penetration and Combination Therapy of Entrectinib for Disseminated ROS1/NTRK-Fusion Positive Pediatric High-Grade Glioma
by Lisa Mayr, Armin S. Guntner, Sibylle Madlener, Maria T. Schmook, Andreas Peyrl, Amedeo A. Azizi, Karin Dieckmann, Dominik Reisinger, Natalia M. Stepien, Kathrin Schramm, Anna Laemmerer, David T. W. Jones, Jonas Ecker, Felix Sahm, Till Milde, Kristian W. Pajtler, Mirjam Blattner-Johnson, Miroslav Strbac, Christian Dorfer, Thomas Czech, Dominik Kirchhofer, Lisa Gabler, Walter Berger, Christine Haberler, Leonhard Müllauer, Wolfgang Buchberger, Irene Slavc, Daniela Lötsch-Gojo and Johannes Gojoadd Show full author list remove Hide full author list
J. Pers. Med. 2020, 10(4), 290; https://doi.org/10.3390/jpm10040290 - 18 Dec 2020
Cited by 22 | Viewed by 4162
Abstract
Targeting oncogenic fusion-genes in pediatric high-grade gliomas (pHGG) with entrectinib has emerged as a highly promising therapeutic approach. Despite ongoing clinical studies, to date, no reports on the treatment of cerebrospinal fluid (CSF) disseminated fusion-positive pHGG exist. Moreover, clinically important information of combination [...] Read more.
Targeting oncogenic fusion-genes in pediatric high-grade gliomas (pHGG) with entrectinib has emerged as a highly promising therapeutic approach. Despite ongoing clinical studies, to date, no reports on the treatment of cerebrospinal fluid (CSF) disseminated fusion-positive pHGG exist. Moreover, clinically important information of combination with other treatment modalities such as intrathecal therapy, radiotherapy and other targeted agents is missing. We report on our clinical experience of entrectinib therapy in two CSF disseminated ROS1/NTRK-fusion-positive pHGG cases. Combination of entrectinib with radiotherapy or intrathecal chemotherapy appears to be safe and has the potential to act synergistically with entrectinib treatment. In addition, we demonstrate CSF penetrance of entrectinib for the first time in patient samples suggesting target engagement even upon CSF dissemination. Moreover, in vitro analyses of two novel cell models derived from one case with NTRK-fusion revealed that combination therapy with either a MEK (trametinib) or a CDK4/6 (abemaciclib) inhibitor synergistically enhances entrectinib anticancer effects. In summary, our comprehensive study, including clinical experience, CSF penetrance and in vitro data on entrectinib therapy of NTRK/ROS1-fusion-positive pHGG, provides essential clinical and preclinical insights into the multimodal treatment of these highly aggressive tumors. Our data suggest that combined inhibition of NTRK/ROS1 and other therapeutic vulnerabilities enhances the antitumor effect, which should be followed-up in further preclinical and clinical studies. Full article
(This article belongs to the Special Issue Molecular Pathology of Cancer: The Past, the Present, and the Future)
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16 pages, 1351 KiB  
Article
Application of a Pharmacogenetics-Based Precision Medicine Model (5SPM) to Psychotic Patients That Presented Poor Response to Neuroleptic Therapy
by Lorena Carrascal-Laso, Manuel Ángel Franco-Martín, María Belén García-Berrocal, Elena Marcos-Vadillo, Santiago Sánchez-Iglesias, Carolina Lorenzo, Almudena Sánchez-Martín, Ignacio Ramos-Gallego, M Jesús García-Salgado and María Isidoro-García
J. Pers. Med. 2020, 10(4), 289; https://doi.org/10.3390/jpm10040289 - 18 Dec 2020
Cited by 4 | Viewed by 2446
Abstract
Antipsychotics are the keystone of the treatment of severe and prolonged mental disorders. However, there are many risks associated with these drugs and not all patients undergo full therapeutic profit from them. The application of the 5 Step Precision Medicine model(5SPM), based on [...] Read more.
Antipsychotics are the keystone of the treatment of severe and prolonged mental disorders. However, there are many risks associated with these drugs and not all patients undergo full therapeutic profit from them. The application of the 5 Step Precision Medicine model(5SPM), based on the analysis of the pharmacogenetic profile of each patient, could be a helpful tool to solve many of the problematics traditionally associated with the neuroleptic treatment. In order to solve this question, a cohort of psychotic patients that showed poor clinical evolution was analyzed. After evaluating the relationship between the prescribed treatment and pharmacogenetic profile of each patient, a great number of pharmacological interactions and pharmacogenetical conflicts were found. After reconsidering the treatment of the conflictive cases, patients showed a substantial reduction on mean daily doses and polytherapy cases, which may cause less risk of adverse effects, greater adherence, and a reduction on economic costs. Full article
(This article belongs to the Special Issue Pharmacogenetics to Avoid Adverse Drug Reactions)
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12 pages, 1160 KiB  
Article
Prediction of Major Depressive Disorder Following Beta-Blocker Therapy in Patients with Cardiovascular Diseases
by Suho Jin, Kristin Kostka, Jose D. Posada, Yeesuk Kim, Seung In Seo, Dong Yun Lee, Nigam H. Shah, Sungwon Roh, Young-Hyo Lim, Sun Geu Chae, Uram Jin, Sang Joon Son, Christian Reich, Peter R. Rijnbeek, Rae Woong Park and Seng Chan You
J. Pers. Med. 2020, 10(4), 288; https://doi.org/10.3390/jpm10040288 - 18 Dec 2020
Cited by 8 | Viewed by 4214
Abstract
Incident depression has been reported to be associated with poor prognosis in patients with cardiovascular disease (CVD), which might be associated with beta-blocker therapy. Because early detection and intervention can alleviate the severity of depression, we aimed to develop a machine learning (ML) [...] Read more.
Incident depression has been reported to be associated with poor prognosis in patients with cardiovascular disease (CVD), which might be associated with beta-blocker therapy. Because early detection and intervention can alleviate the severity of depression, we aimed to develop a machine learning (ML) model predicting the onset of major depressive disorder (MDD). A model based on L1 regularized logistic regression was trained against the South Korean nationwide administrative claims database to identify risk factors for the incident MDD after beta-blocker therapy in patients with CVD. We identified 50,397 patients initiating beta-blockers for CVD, with 774 patients developing MDD within 365 days after initiating beta-blocker therapy. An area under the receiver operating characteristic curve (AUC) of 0.74 was achieved. A history of non-selective beta-blockers and factors related to anxiety disorder, sleeping problems, and other chronic diseases were the most strong predictors. AUCs of 0.62–0.71 were achieved in the external validation conducted on six independent electronic health records and claims databases in the USA and South Korea. In conclusion, an ML model that identifies patients at high-risk for incident MDD was developed. Application of ML to identify susceptible patients for adverse events of treatment may serve as an important approach for personalized medicine. Full article
(This article belongs to the Special Issue Personalized Medicine for Cardiovascular Disease)
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11 pages, 2463 KiB  
Article
Germline Genetic Association between Stromal Interaction Molecule 1 (STIM1) and Clinical Outcomes in Breast Cancer Patients
by Chi-Cheng Huang, Min-Rou Lin, Yu-Chen Yang, Yu-Wen Hsu, Henry Sung-Ching Wong and Wei-Chiao Chang
J. Pers. Med. 2020, 10(4), 287; https://doi.org/10.3390/jpm10040287 - 17 Dec 2020
Cited by 1 | Viewed by 2105
Abstract
Among all cancers in women, breast cancer has the highest incidence. The mortality of breast cancer is highly associated with metastasis. Migration and malignant transformation of cancer cells have been reported to be modulated by store-operated calcium (SOC) channels, which control calcium signaling [...] Read more.
Among all cancers in women, breast cancer has the highest incidence. The mortality of breast cancer is highly associated with metastasis. Migration and malignant transformation of cancer cells have been reported to be modulated by store-operated calcium (SOC) channels, which control calcium signaling and cell proliferation pathways. Stromal interaction molecule 1 (STIM1) is a calcium sensor in the endoplasmic reticulum, triggering the activation of store-operated calcium signaling. However, the clinical relevance of STIM1 in breast cancer is still unclear. Here, we recruited 348 breast cancer patients and conducted a genetic association study to address this question. Four tagging germline single nucleotide variants (SNVs) in STIM1 were selected and RNA sequencing data of 525 breast cancer samples from The Cancer Genome Atlas (TCGA) database were evaluated. The results show that rs2304891 and rs3750996 were correlated with clinical stage of breast cancer. Expression quantitative trait loci (eQTL) analysis indicated that risk G allele of STIM1 contributed to the higher expression of STIM1. In addition, we found an increased risk of rs2304891 G allele and rs3750996 A allele in estrogen receptor (ER) positive and progesterone receptor (PR) positive patients. In conclusion, our results suggest that germline SNV, rs2304891 and rs3750996 as well as STIM1 expression are important biomarkers for the prediction of clinical outcomes in breast cancer patients. Full article
(This article belongs to the Special Issue Molecular Pathology of Cancer: The Past, the Present, and the Future)
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11 pages, 1511 KiB  
Article
Prediction of Stroke Outcome Using Natural Language Processing-Based Machine Learning of Radiology Report of Brain MRI
by Tak Sung Heo, Yu Seop Kim, Jeong Myeong Choi, Yeong Seok Jeong, Soo Young Seo, Jun Ho Lee, Jin Pyeong Jeon and Chulho Kim
J. Pers. Med. 2020, 10(4), 286; https://doi.org/10.3390/jpm10040286 - 16 Dec 2020
Cited by 29 | Viewed by 4616
Abstract
Brain magnetic resonance imaging (MRI) is useful for predicting the outcome of patients with acute ischemic stroke (AIS). Although deep learning (DL) using brain MRI with certain image biomarkers has shown satisfactory results in predicting poor outcomes, no study has assessed the usefulness [...] Read more.
Brain magnetic resonance imaging (MRI) is useful for predicting the outcome of patients with acute ischemic stroke (AIS). Although deep learning (DL) using brain MRI with certain image biomarkers has shown satisfactory results in predicting poor outcomes, no study has assessed the usefulness of natural language processing (NLP)-based machine learning (ML) algorithms using brain MRI free-text reports of AIS patients. Therefore, we aimed to assess whether NLP-based ML algorithms using brain MRI text reports could predict poor outcomes in AIS patients. This study included only English text reports of brain MRIs examined during admission of AIS patients. Poor outcome was defined as a modified Rankin Scale score of 3–6, and the data were captured by trained nurses and physicians. We only included MRI text report of the first MRI scan during the admission. The text dataset was randomly divided into a training and test dataset with a 7:3 ratio. Text was vectorized to word, sentence, and document levels. In the word level approach, which did not consider the sequence of words, and the “bag-of-words” model was used to reflect the number of repetitions of text token. The “sent2vec” method was used in the sensation-level approach considering the sequence of words, and the word embedding was used in the document level approach. In addition to conventional ML algorithms, DL algorithms such as the convolutional neural network (CNN), long short-term memory, and multilayer perceptron were used to predict poor outcomes using 5-fold cross-validation and grid search techniques. The performance of each ML classifier was compared with the area under the receiver operating characteristic (AUROC) curve. Among 1840 subjects with AIS, 645 patients (35.1%) had a poor outcome 3 months after the stroke onset. Random forest was the best classifier (0.782 of AUROC) using a word-level approach. Overall, the document-level approach exhibited better performance than did the word- or sentence-level approaches. Among all the ML classifiers, the multi-CNN algorithm demonstrated the best classification performance (0.805), followed by the CNN (0.799) algorithm. When predicting future clinical outcomes using NLP-based ML of radiology free-text reports of brain MRI, DL algorithms showed superior performance over the other ML algorithms. In particular, the prediction of poor outcomes in document-level NLP DL was improved more by multi-CNN and CNN than by recurrent neural network-based algorithms. NLP-based DL algorithms can be used as an important digital marker for unstructured electronic health record data DL prediction. Full article
(This article belongs to the Section Omics/Informatics)
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36 pages, 370 KiB  
Review
Prediction of the Acute or Late Radiation Toxicity Effects in Radiotherapy Patients Using Ex Vivo Induced Biodosimetric Markers: A Review
by Volodymyr Vinnikov, Manoor Prakash Hande, Ruth Wilkins, Andrzej Wojcik, Eduardo Zubizarreta and Oleg Belyakov
J. Pers. Med. 2020, 10(4), 285; https://doi.org/10.3390/jpm10040285 - 16 Dec 2020
Cited by 12 | Viewed by 3096
Abstract
A search for effective methods for the assessment of patients’ individual response to radiation is one of the important tasks of clinical radiobiology. This review summarizes available data on the use of ex vivo cytogenetic markers, typically used for biodosimetry, for the prediction [...] Read more.
A search for effective methods for the assessment of patients’ individual response to radiation is one of the important tasks of clinical radiobiology. This review summarizes available data on the use of ex vivo cytogenetic markers, typically used for biodosimetry, for the prediction of individual clinical radiosensitivity (normal tissue toxicity, NTT) in cells of cancer patients undergoing therapeutic irradiation. In approximately 50% of the relevant reports, selected for the analysis in peer-reviewed international journals, the average ex vivo induced yield of these biodosimetric markers was higher in patients with severe reactions than in patients with a lower grade of NTT. Also, a significant correlation was sometimes found between the biodosimetric marker yield and the severity of acute or late NTT reactions at an individual level, but this observation was not unequivocally proven. A similar controversy of published results was found regarding the attempts to apply G2- and γH2AX foci assays for NTT prediction. A correlation between ex vivo cytogenetic biomarker yields and NTT occurred most frequently when chromosome aberrations (not micronuclei) were measured in lymphocytes (not fibroblasts) irradiated to relatively high doses (4–6 Gy, not 2 Gy) in patients with various grades of late (not early) radiotherapy (RT) morbidity. The limitations of existing approaches are discussed, and recommendations on the improvement of the ex vivo cytogenetic testing for NTT prediction are provided. However, the efficiency of these methods still needs to be validated in properly organized clinical trials involving large and verified patient cohorts. Full article
(This article belongs to the Special Issue Radiation Response Biomarkers for Individualised Cancer Treatments)
15 pages, 2251 KiB  
Article
Whole Body 3.0 T Magnetic Resonance Imaging in Lymphomas: Comparison of Different Sequence Combinations for Staging Hodgkin’s and Diffuse Large B Cell Lymphomas
by Arash Latifoltojar, Mark K. J. Duncan, Maria Klusmann, Harbir Sidhu, Alan Bainbridge, Deena Neriman, Francesco Fraioli, Jonathan Lambert, Kirit M. Ardeshna and Shonit Punwani
J. Pers. Med. 2020, 10(4), 284; https://doi.org/10.3390/jpm10040284 - 16 Dec 2020
Cited by 5 | Viewed by 2413
Abstract
To investigate the diagnostic value of different whole-body magnetic resonance imaging (WB-MRI) protocols for staging Hodgkin and diffuse-large B-cell lymphomas (HL and DLBCL), twenty-two patients (M/F 12/10, median age 32, range 22–87, HL/DLBCL 14/8) underwent baseline WB-MRI and 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) [...] Read more.
To investigate the diagnostic value of different whole-body magnetic resonance imaging (WB-MRI) protocols for staging Hodgkin and diffuse-large B-cell lymphomas (HL and DLBCL), twenty-two patients (M/F 12/10, median age 32, range 22–87, HL/DLBCL 14/8) underwent baseline WB-MRI and 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET) fused with computed tomography (CT) scan 18F-FDG-PET-CT. The 3.0 T WB-MRI was performed using pre-contrast modified Dixon (mDixon), T2-weighted turbo-spin-echo (TSE), diffusion-weighted-imaging (DWI), dynamic-contrast-enhanced (DCE) liver/spleen, contrast-enhanced (CE) lung MRI and CE whole-body mDixon. WB-MRI scans were divided into: (1) “WB-MRI DWI+IP”: whole-body DWI + in-phase mDixon (2) “WB-MRI T2-TSE”: whole-body T2-TSE (3) “WB-MRI Post-C”: whole-body CE mDixon + DCE liver/spleen and CE lung mDixon (4) “WB-MRI All “: the entire protocol. Two radiologists evaluated WB-MRIs at random, independently and then in consensus. Two nuclear-medicine-physicians reviewed 18F-FDG PET-CT in consensus. An enhanced-reference-standard (ERS) was derived using all available baseline and follow-up imaging. The sensitivity and specificity of WB-MRI protocols for nodal and extra-nodal staging was derived against the ERS. Agreement between the WB-MRI protocols and the ERS for overall staging was assessed using kappa statistic. For consensus WB-MRI, the sensitivity and specificity for nodal staging were 75%, 98% for WB-MRI DWI+IP, 76%, 98% for WB-MRI Post-C, 83%, 99% for WB-MRI T2-TSE and 87%, 100% for WB-MRI All. The sensitivity and specificity for extra-nodal staging were 67% 100% for WB-MRI DWI+IP, 89%, 100% for WB-MRI Post-C, 89%, 100% for WB-MRI T2-TSE and 100%, 100% for the WB-MRI All. The consensus WB-MRI All read had perfect agreement with the ERS for overall staging [kappa = 1.00 (95% CI: 1.00-1.00)]. The best diagnostic performance is achieved combining all available WB-MRI sequences. Full article
(This article belongs to the Special Issue Biomedical Imaging and Cancers)
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14 pages, 825 KiB  
Article
Brain Responses to Emotional Stimuli after Eicosapentaenoic Acid and Docosahexaenoic Acid Treatments in Major Depressive Disorder: Toward Personalized Medicine with Anti-Inflammatory Nutraceuticals
by Cheng-Hao Tu, Chun-Ming Chen, Chuan-Chih Yang, Piotr Gałecki and Kuan-Pin Su
J. Pers. Med. 2020, 10(4), 283; https://doi.org/10.3390/jpm10040283 - 16 Dec 2020
Cited by 7 | Viewed by 2729
Abstract
N-3 polyunsaturated fatty acid supplements improve the symptoms of major depressive disorder (MDD) in randomized-controlled trials and meta-analyses, with the higher efficacy from anti-inflammatory eicosapentaenoic acid (EPA) than brain-dominant docosahexaenoic acid (DHA). To investigate the specific brain mechanisms of the anti-inflammatory anti-depressant nutraceutical [...] Read more.
N-3 polyunsaturated fatty acid supplements improve the symptoms of major depressive disorder (MDD) in randomized-controlled trials and meta-analyses, with the higher efficacy from anti-inflammatory eicosapentaenoic acid (EPA) than brain-dominant docosahexaenoic acid (DHA). To investigate the specific brain mechanisms of the anti-inflammatory anti-depressant nutraceutical compounds, we recruited 24 MDD subjects in this double-blind, head-to-head study with a 12-week EPA or DHA treatment (clinical trial registration number: NCT03871088). The depression severity was assessed by Hamilton depression rating scale (HAM-D). Brain responses to emotional stimuli were measured by a 3-Tesla MRI. The correlation between HAM-D scores and brain responses also were tested. Compared to 18 healthy controls, the brain responses of untreated 24 MDD patients mainly revealed hypoactivity in the regions associated with emotion perception and emotion control when processing positive emotion. After treatment, more remitted MDD patients have been observed in the EPA as compared to the DHA groups. In addition, the EPA, but not DHA, treatment revealed increased activity in the regions associated with emotion perception and cognitive control when processing positive emotion. The correlation analysis further revealed negative correlation between HAM-D scores and brain responses in cognitive control regions. The results of this study may imply the compensatory brain responses of cognitive and emotion controls by EPA but not DHA and underpin personalized medicine with anti-inflammatory nutraceuticals toward depression treatments. Full article
(This article belongs to the Special Issue Personalized Medicine for Neuroimmunology and Epigenetics in Depressive Disorders)
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44 pages, 3477 KiB  
Review
Digital Phenotyping and Patient-Generated Health Data for Outcome Measurement in Surgical Care: A Scoping Review
by Prakash Jayakumar, Eugenia Lin, Vincent Galea, Abraham J. Mathew, Nikhil Panda, Imelda Vetter and Alex B. Haynes
J. Pers. Med. 2020, 10(4), 282; https://doi.org/10.3390/jpm10040282 - 15 Dec 2020
Cited by 18 | Viewed by 3952
Abstract
Digital phenotyping—the moment-by-moment quantification of human phenotypes in situ using data related to activity, behavior, and communications, from personal digital devices, such as smart phones and wearables—has been gaining interest. Personalized health information captured within free-living settings using such technologies may better enable [...] Read more.
Digital phenotyping—the moment-by-moment quantification of human phenotypes in situ using data related to activity, behavior, and communications, from personal digital devices, such as smart phones and wearables—has been gaining interest. Personalized health information captured within free-living settings using such technologies may better enable the application of patient-generated health data (PGHD) to provide patient-centered care. The primary objective of this scoping review is to characterize the application of digital phenotyping and digitally captured active and passive PGHD for outcome measurement in surgical care. Secondarily, we synthesize the body of evidence to define specific areas for further work. We performed a systematic search of four bibliographic databases using terms related to “digital phenotyping and PGHD,” “outcome measurement,” and “surgical care” with no date limits. We registered the study (Open Science Framework), followed strict inclusion/exclusion criteria, performed screening, extraction, and synthesis of results in line with the PRISMA Extension for Scoping Reviews. A total of 224 studies were included. Published studies have accelerated in the last 5 years, originating in 29 countries (mostly from the USA, n = 74, 33%), featuring original prospective work (n = 149, 66%). Studies spanned 14 specialties, most commonly orthopedic surgery (n = 129, 58%), and had a postoperative focus (n = 210, 94%). Most of the work involved research-grade wearables (n = 130, 58%), prioritizing the capture of activity (n = 165, 74%) and biometric data (n = 100, 45%), with a view to providing a tracking/monitoring function (n = 115, 51%) for the management of surgical patients. Opportunities exist for further work across surgical specialties involving smartphones, communications data, comparison with patient-reported outcome measures (PROMs), applications focusing on prediction of outcomes, monitoring, risk profiling, shared decision making, and surgical optimization. The rapidly evolving state of the art in digital phenotyping and capture of PGHD offers exciting prospects for outcome measurement in surgical care pending further work and consideration related to clinical care, technology, and implementation. Full article
(This article belongs to the Special Issue PROomics: Patient Reported Outcome (PRO) and Self-Tracking for Personalized Medicine)
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15 pages, 3705 KiB  
Article
A Wide Spectrum of Genetic Disorders Causing Severe Childhood Epilepsy in Taiwan: A Case Series of Ultrarare Genetic Cause and Novel Mutation Analysis in a Pilot Study
by Syuan-Yu Hong, Jiann-Jou Yang, Shuan-Yow Li and Inn-Chi Lee
J. Pers. Med. 2020, 10(4), 281; https://doi.org/10.3390/jpm10040281 - 15 Dec 2020
Cited by 15 | Viewed by 3096
Abstract
Background: Pediatric epileptic encephalopathy and severe neurological disorders comprise a group of heterogenous diseases. We used whole-exome sequencing (WES) to identify genetic defects in pediatric patients. Methods: Patients with refractory seizures using ≥2 antiepileptic drugs (AEDs) receiving one AED and having neurodevelopmental regression [...] Read more.
Background: Pediatric epileptic encephalopathy and severe neurological disorders comprise a group of heterogenous diseases. We used whole-exome sequencing (WES) to identify genetic defects in pediatric patients. Methods: Patients with refractory seizures using ≥2 antiepileptic drugs (AEDs) receiving one AED and having neurodevelopmental regression or having severe neurological or neuromuscular disorders with unidentified causes were enrolled, of which 54 patients fulfilled the inclusion criteria, were enrolled, and underwent WES. Results: Genetic diagnoses were confirmed in 24 patients. In the seizure group, KCNQ2, SCN1A, TBCID 24, GRIN1, IRF2BPL, MECP2, OSGEP, PACS1, PIGA, PPP1CB, SMARCA4, SUOX, SZT2, UBE3A, 16p13.11 microdeletion, [4p16.3p16.1(68,345–7,739,782)X1, 17q25.1q25.3(73,608,322–81,041,938)X3], and LAMA2 were identified. In the nonseizure group, SCN2A, SPTBN2, DMD, and FBN1 were identified. Ten novel mutations were identified. The recurrent genes included SCN1A, KCNQ2, and TBCID24. Male pediatric patients had a significantly higher (57% vs. 29%; p < 0.05, odds ratio = 3.18) yield than their female counterparts. Seventeen genes were identified from the seizure groups, of which 82% were rare genetic etiologies for childhood seizure and did not appear recurrently in the case series. Conclusions: Wide genetic variation was identified for severe childhood seizures by WES. WES had a high yield, particularly in male infantile patients. Full article
(This article belongs to the Special Issue Molecular Neurobiology of Neurodegenerative Diseases)
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10 pages, 348 KiB  
Article
Hormonal Contraceptive Treatment May Reduce the Risk of Fibromyalgia in Women with Dysmenorrhea: A Cohort Study
by Cheng-Hao Tu, Cheng-Li Lin, Su-Tso Yang, Wei-Chih Shen and Yi-Hung Chen
J. Pers. Med. 2020, 10(4), 280; https://doi.org/10.3390/jpm10040280 - 14 Dec 2020
Cited by 7 | Viewed by 2603
Abstract
Dysmenorrhea is the most common gynecological disorder for women in the reproductive age. Study has indicated that dysmenorrhea might be a general risk factor of chronic pelvic pain and even chronic non-pelvic pain, such as fibromyalgia. We used the Longitudinal Health Insurance Database [...] Read more.
Dysmenorrhea is the most common gynecological disorder for women in the reproductive age. Study has indicated that dysmenorrhea might be a general risk factor of chronic pelvic pain and even chronic non-pelvic pain, such as fibromyalgia. We used the Longitudinal Health Insurance Database 2000 from the Taiwan National Health Research Institutes Database to investigate whether women with dysmenorrhea have a higher risk of fibromyalgia and whether treatment of dysmenorrhea reduced the risk of fibromyalgia. The dysmenorrhea cohort was matched with a non-dysmenorrhea cohort at a 1:1 ratio based on gender, age, and the year of entry study by frequency matching. Multivariable Cox proportional hazard regression models were used to assess the risk of fibromyalgia, with controlling for potential confounding variables such as age, comorbidities, and medication use. After controlling confounding variables, results revealed that women with dysmenorrhea have a significantly higher risk of fibromyalgia than women without dysmenorrhea. However, only treatment of dysmenorrhea with hormonal contraceptives reduce the risk of fibromyalgia. These results indicated that dysmenorrhea may be a risk factor of fibromyalgia, whereas personalized medicine for treatment of dysmenorrhea may be the key to reduce the risk of fibromyalgia. Future studies are needed to identify the causes and prevention strategies in detail. Full article
(This article belongs to the Special Issue Chronic Pain)
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13 pages, 756 KiB  
Article
Profiling Patients by Intensity of Nursing Care: An Operative Approach Using Machine Learning
by Honoria Ocagli, Corrado Lanera, Giulia Lorenzoni, Ilaria Prosepe, Danila Azzolina, Sabrina Bortolotto, Lucia Stivanello, Mario Degan and Dario Gregori
J. Pers. Med. 2020, 10(4), 279; https://doi.org/10.3390/jpm10040279 - 14 Dec 2020
Cited by 3 | Viewed by 2287
Abstract
Physical function is a patient-oriented indicator and can be considered a proxy for the assignment of healthcare personnel. The study aims to create an algorithm that classifies patients into homogeneous groups according to physical function. A two-step machine-learning algorithm was applied to administrative [...] Read more.
Physical function is a patient-oriented indicator and can be considered a proxy for the assignment of healthcare personnel. The study aims to create an algorithm that classifies patients into homogeneous groups according to physical function. A two-step machine-learning algorithm was applied to administrative data recorded between 2015 and 2018 at the University Hospital of Padova. A clustering-large-applications (CLARA) algorithm was used to partition patients into homogeneous groups. Then, machine learning technique (MLT) classifiers were used to categorize the doubtful records. Based on the results of the CLARA algorithm, records were divided into three groups according to the Barthel index: <45, >65, ≥45 and ≤65. The support vector machine was the MLT showing the best performance among doubtful records, reaching an accuracy of 66%. The two-step algorithm, since it splits patients into low and high resource consumption, could be a useful tool for organizing healthcare personnel allocation according to the patients’ assistance needs. Full article
(This article belongs to the Section Epidemiology)
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15 pages, 5587 KiB  
Article
One-Stage Soft Tissue Reconstruction Following Sarcoma Excision: A Personalized Multidisciplinary Approach Called “Orthoplasty”
by Andrea Angelini, Cesare Tiengo, Regina Sonda, Antonio Berizzi, Franco Bassetto and Pietro Ruggieri
J. Pers. Med. 2020, 10(4), 278; https://doi.org/10.3390/jpm10040278 - 14 Dec 2020
Cited by 11 | Viewed by 6039
Abstract
Background and Objectives. Wide surgical resection is a relevant factor for local control in sarcomas. Plastic surgery is mandatory in demanding reconstructions. We analyzed patients treated by a multidisciplinary team to evaluate indications and surgical approaches, complications and therapeutic/functional outcomes. Methods. [...] Read more.
Background and Objectives. Wide surgical resection is a relevant factor for local control in sarcomas. Plastic surgery is mandatory in demanding reconstructions. We analyzed patients treated by a multidisciplinary team to evaluate indications and surgical approaches, complications and therapeutic/functional outcomes. Methods. We analyzed 161 patients (86 males (53%), mean age 56 years) from 2006 to 2017. Patients were treated for their primary tumor (120, 75.5%) or after unplanned excision/recurrence (41, 25.5%). Sites included lower limbs (36.6%), upper limbs (19.2%), head/neck (21.1%), trunk (14.9%) and pelvis (8.1%). Orthoplasty has been considered for flaps (54), skin grafts (42), wide excisions (40) and other procedures (25). Results. At a mean follow-up of 5.3 years (range 2–10.5), patients continuously showed no evidence of disease (NED) in 130 cases (80.7%), were alive with disease (AWD) in 10 cases (6.2%) and were dead with disease (DWD) in 21 cases (13.0%). Overall, 62 patients (38.5%) developed a complication (56 minor (90.3%) and 6 major (9.7%)). Flap loss occurred in 5/48 patients (10.4%). The mean Musculoskeletal Tumor Society (MSTS) and Toronto Extremity Salvage Score (TESS) was 74.8 ± 14 and 79.1 ± 13, respectively. Conclusions. Orthoplasty is a combined approach effective in management of sarcoma patients, maximizing adequate surgical resection, limb salvaging and functional recovery. One-stage reconstructions are technically feasible and are not associated with increased risk of complications. Full article
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16 pages, 1574 KiB  
Review
Mass Spectrometry-Based Omics for the Characterization of Triple-Negative Breast Cancer Bio-Signature
by Ioana-Ecaterina Pralea, Radu-Cristian Moldovan, Adrian-Bogdan Țigu, Corina Ionescu and Cristina-Adela Iuga
J. Pers. Med. 2020, 10(4), 277; https://doi.org/10.3390/jpm10040277 - 12 Dec 2020
Cited by 8 | Viewed by 3250
Abstract
Triple-negative breast cancer (TNBC) represents an unmet medical need due to a high rate of metastatic occurrence and poor overall survival, pathology aggressiveness, heterogeneous clinical behavior and limited cytotoxic chemotherapy options available because of the absence of targetable receptors. The current standard of [...] Read more.
Triple-negative breast cancer (TNBC) represents an unmet medical need due to a high rate of metastatic occurrence and poor overall survival, pathology aggressiveness, heterogeneous clinical behavior and limited cytotoxic chemotherapy options available because of the absence of targetable receptors. The current standard of care in TNBC is represented by chemotherapy and surgery associated with low overall survival and high relapse rates. Hopes of overcoming current limited and unspecific approaches of TNBC therapy lie in studying the metabolic rewiring of these types of breast cancer, thus understanding the mechanisms involved in the occurrence and progression of the disease. Due to its heterogeneity, a clinically relevant sub-classification of this type of breast cancer based on biomarker panels is greatly needed in order to guide treatment decisions. Mass spectrometry-based omics may provide very useful tools to address the current needs of targetable biomarker discovery and validation. The present review aims to provide a comprehensive view of the current clinical diagnosis and therapy of TNBC highlighting the need for a new approach. Therefore, this paper offers a detailed mass spectrometry-based snapshot of TNBC metabolic adjustment, emphasizing a complex network of variables governing the diverse and aggressive clinical behavior of TNBC. Full article
(This article belongs to the Special Issue Integrative Multi-Omics for Novel Clinical Insights)
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14 pages, 2581 KiB  
Article
A Network-Based Mixed Methods Approach to Analyze Current Perspectives on Personalized Oncological Medicine in Austria
by Ines Viktoria Stelzer, Anna Sierawska, Alena Buyx and Judit Simon
J. Pers. Med. 2020, 10(4), 276; https://doi.org/10.3390/jpm10040276 - 12 Dec 2020
Cited by 3 | Viewed by 2019
Abstract
Personalized medicine (PM) to tailor healthcare (HC) to the individual, is a promising but challenging concept. So far, no study exists investigating stakeholders’ perspectives on PM in oncology in Austria potentially hindering implementation, which was the aim of this study. We performed semi-structured [...] Read more.
Personalized medicine (PM) to tailor healthcare (HC) to the individual, is a promising but challenging concept. So far, no study exists investigating stakeholders’ perspectives on PM in oncology in Austria potentially hindering implementation, which was the aim of this study. We performed semi-structured interviews among experts (n = 14) and cancer patients (n = 2) of the Vienna General Hospital and the Medical University of Vienna and analyzed them by a mixed methods network theoretical approach. Study results show a great variety of topics addressed by the interviewees. Clear differences in the topic selection between patients and experts could be observed. Patient-doctor relationship was the most prominent theme among experts, whereas HC systems and public health in PM was more relevant for the patients. Although promising new molecular pathology methods were explicitly mentioned, the experts believed that their practical implementation and the implementation of PM in standard care will take a long time in Austria. A variety of concerns regarding PM were mentioned by the experts, including communication issues and knowledge gaps. Besides important insights into the current situation of PM in Austria, the study has shown that network theory is a powerful tool for analyzing qualitative interview data. Full article
(This article belongs to the Special Issue Molecular Pathology of Cancer: The Past, the Present, and the Future)
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19 pages, 1475 KiB  
Article
Autism Spectrum Disorder and Childhood Apraxia of Speech: Early Language-Related Hallmarks across Structural MRI Study
by Eugenia Conti, Alessandra Retico, Letizia Palumbo, Giovanna Spera, Paolo Bosco, Laura Biagi, Simona Fiori, Michela Tosetti, Paola Cipriani, Giovanni Cioni, Filippo Muratori, Anna Chilosi and Sara Calderoni
J. Pers. Med. 2020, 10(4), 275; https://doi.org/10.3390/jpm10040275 - 12 Dec 2020
Cited by 21 | Viewed by 6534
Abstract
Autism Spectrum Disorder (ASD) and Childhood Apraxia of Speech (CAS) are developmental disorders with distinct diagnostic criteria and different epidemiology. However, a common genetic background as well as overlapping clinical features between ASD and CAS have been recently reported. To date, brain structural [...] Read more.
Autism Spectrum Disorder (ASD) and Childhood Apraxia of Speech (CAS) are developmental disorders with distinct diagnostic criteria and different epidemiology. However, a common genetic background as well as overlapping clinical features between ASD and CAS have been recently reported. To date, brain structural language-related abnormalities have been detected in both the conditions, but no study directly compared young children with ASD, CAS and typical development (TD). In the current work, we aim: (i) to test the hypothesis that ASD and CAS display neurostructural differences in comparison with TD through morphometric Magnetic Resonance Imaging (MRI)-based measures (ASD vs. TD and CAS vs. TD); (ii) to investigate early possible disease-specific brain structural patterns in the two clinical groups (ASD vs. CAS); (iii) to evaluate predictive power of machine-learning (ML) techniques in differentiating the three samples (ASD, CAS, TD). We retrospectively analyzed the T1-weighted brain MRI scans of 68 children (age range: 34–74 months) grouped into three cohorts: (1) 26 children with ASD (mean age ± standard deviation: 56 ± 11 months); (2) 24 children with CAS (57 ± 10 months); (3) 18 children with TD (55 ± 13 months). Furthermore, a ML analysis based on a linear-kernel Support Vector Machine (SVM) was performed. All but one brain structures displayed significant higher volumes in both ASD and CAS children than TD peers. Specifically, ASD alterations involved fronto-temporal regions together with basal ganglia and cerebellum, while CAS alterations are more focused and shifted to frontal regions, suggesting a possible speech-related anomalies distribution. Caudate, superior temporal and hippocampus volumes directly distinguished the two conditions in terms of greater values in ASD compared to CAS. The ML analysis identified significant differences in brain features between ASD and TD children, whereas only some trends in the ML classification capability were detected in CAS as compared to TD peers. Similarly, the MRI structural underpinnings of two clinical groups were not significantly different when evaluated with linear-kernel SVM. Our results may represent the first step towards understanding shared and specific neural substrate in ASD and CAS conditions, which subsequently may contribute to early differential diagnosis and tailoring specific early intervention. Full article
(This article belongs to the Special Issue Predicting Psychopathological Onset: Early Signs of Neuropsychiatric Diseases)
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16 pages, 553 KiB  
Article
Clinical and Electrophysiological Hints to TMS in De Novo Patients with Parkinson’s Disease and Progressive Supranuclear Palsy
by Francesco Fisicaro, Giuseppe Lanza, Mariagiovanna Cantone, Raffaele Ferri, Giovanni Pennisi, Alessandra Nicoletti, Mario Zappia, Rita Bella and Manuela Pennisi
J. Pers. Med. 2020, 10(4), 274; https://doi.org/10.3390/jpm10040274 - 12 Dec 2020
Cited by 25 | Viewed by 2858
Abstract
Background: Transcranial magnetic stimulation (TMS) can non-invasively probe cortical excitability in movement disorders, although clinical significance is still controversial, especially at early stages. We compare single-pulse TMS in two prototypic synucleinopathy and tauopathy—i.e., Parkinson’s disease (PD) and Progressive Supranuclear Palsy (PSP), respectively—to find [...] Read more.
Background: Transcranial magnetic stimulation (TMS) can non-invasively probe cortical excitability in movement disorders, although clinical significance is still controversial, especially at early stages. We compare single-pulse TMS in two prototypic synucleinopathy and tauopathy—i.e., Parkinson’s disease (PD) and Progressive Supranuclear Palsy (PSP), respectively—to find neurophysiological differences and identify early measures associated with cognitive impairment. Methods: 28 PD and 23 PSP de novo patients were age-matched with 28 healthy controls, all right-handed and drug-free. Amplitude and latency of motor evoked potentials (MEP), central motor conduction time, resting motor threshold (rMT), and cortical silent period (CSP) were recorded through a figure-of-eight coil from the First Dorsal Interosseous muscle (FDI), bilaterally. Results: Mini Mental Examination and Frontal Assessment Battery (FAB) scored worse in PSP; PD had worse FAB than controls. Higher MEP amplitude from right FDI in PD and PSP than controls was found, without difference between them. CSP was bilaterally longer in patients than controls, but similar between patient groups. A positive correlation between FAB and rMT was observed in PSP, bilaterally. Conclusions: Despite the small sample size, PD and PSP might share, at early stage, a similar global electrocortical asset. rMT might detect and possibly predict cognitive deterioration in PSP. Full article
(This article belongs to the Special Issue Clinical Neurophysiology, Neuroimaging, and Neuromodulation of Neuropsychiatric Disorders)
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9 pages, 21609 KiB  
Article
Comparison between Additive and Subtractive CAD-CAM Technique to Produce Orthognathic Surgical Splints: A Personalized Approach
by Giuseppe Palazzo, Vincenzo Ronsivalle, Giacomo Oteri, Antonino Lo Giudice, Corrado Toro, Paola Campagna, Romeo Patini, Salvatore Bocchieri, Alberto Bianchi and Gaetano Isola
J. Pers. Med. 2020, 10(4), 273; https://doi.org/10.3390/jpm10040273 - 11 Dec 2020
Cited by 7 | Viewed by 3865
Abstract
The present study aimed to evaluate the accuracy of digitally designed surgical splints generated with milling technology (material subtractive procedure) and with 3D printing technology (material additive procedure) through a customized approach in the planning of surgical orthognathic splints. Cone beam computed tomography [...] Read more.
The present study aimed to evaluate the accuracy of digitally designed surgical splints generated with milling technology (material subtractive procedure) and with 3D printing technology (material additive procedure) through a customized approach in the planning of surgical orthognathic splints. Cone beam computed tomography (CBCT) examinations and scanned dental models of 10 subjects who had required surgical treatment of skeletal malocclusion were included. Simulation of the orthognathic surgery was performed according to dento-skeletal and aesthetic characteristics of the subjects and the visual treatment objective (VTO), using Dolphin3D software (Dolphin Imaging, version 11.0, Chatsworth, CA, USA). Afterward, the Appliance Designer software (3Shape A/S, Copenhagen, Denmark) was used to digitally design the surgical splints that were generated twice using laser stereolithography technology (DWS 0.29D, DWS, Vicenza, Italy) and milling technology (Sirona inLab MC X5). Finally, each physical splint was digitalized using a desktop scanner (D500 3D, 3Shape A/S, Copenhagen, Denmark) in order to perform deviation analysis using the original project as a reference. The relative percentage of matching (trueness) was calculated (Geomagic Control X software (3D Systems, version 2018.1.1, 3D Systems, Rock Hill, SC, USA). An Independent Student’s t-test was used to statistically analyze the data. The milled splints showed a lower value of root to mean square (RMS) relative to the original project (0.20 mm ± 0.018) compared to the prototyped splints (0.31 ± 0.021) (p < 0.001). According to the present findings, surgical splints generated with milling technology present higher trueness compared with 3D printing technology. Full article
(This article belongs to the Special Issue Molecular Diagnosis and New Therapeutic Approach of Oral Diseases)
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19 pages, 1961 KiB  
Article
Precision Medicine for the Management of Therapy Refractory Colorectal Cancer
by Hossein Taghizadeh, Robert M. Mader, Leonhard Müllauer, Friedrich Erhart, Alexandra Kautzky-Willer and Gerald W. Prager
J. Pers. Med. 2020, 10(4), 272; https://doi.org/10.3390/jpm10040272 - 11 Dec 2020
Cited by 5 | Viewed by 2309
Abstract
In this analysis, we examined the efficacy, feasibility, and limitations of molecular-based targeted therapies in heavily pretreated metastatic colorectal cancer (mCRC) patients after failure of all standard treatments. In this single-center, real-world retrospective analysis of our platform for precision medicine, we mapped the [...] Read more.
In this analysis, we examined the efficacy, feasibility, and limitations of molecular-based targeted therapies in heavily pretreated metastatic colorectal cancer (mCRC) patients after failure of all standard treatments. In this single-center, real-world retrospective analysis of our platform for precision medicine, we mapped the molecular profiles of 60 mCRC patients. Tumor samples of the patients were analyzed using next-generation sequencing panels of mutation hotspots, microsatellite instability testing, and immunohistochemistry. All profiles were reviewed by a multidisciplinary team to provide a targeted treatment recommendation after consensus discussion. In total, we detected 166 mutations in 53 patients. The five most frequently found mutations were TP53, KRAS, APC, PIK3CA, and PTEN. In 28 cases (47% of all patients), a molecularly targeted therapy could be recommended. Eventually, 12 patients (20%) received the recommended therapy. Six patients (10%) had a clinical benefit. The median time to treatment failure was 3.1 months. Our study demonstrates the feasibility and applicability of using targeted therapies in daily clinical practice for heavily pretreated mCRC patients. This could be used as a targeted treatment option in half of the patients. Full article
(This article belongs to the Special Issue Gastrointestinal Cancers and Personalized Medicine)
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14 pages, 1503 KiB  
Article
Identification of Metabolic Biomarkers in Relation to Methotrexate Response in Early Rheumatoid Arthritis
by Helen R. Gosselt, Ittai B. Muller, Gerrit Jansen, Michel van Weeghel, Frédéric M. Vaz, Johanna M. W. Hazes, Sandra G. Heil and Robert de Jonge
J. Pers. Med. 2020, 10(4), 271; https://doi.org/10.3390/jpm10040271 - 10 Dec 2020
Cited by 12 | Viewed by 2880
Abstract
This study aimed to identify baseline metabolic biomarkers for response to methotrexate (MTX) therapy in rheumatoid arthritis (RA) using an untargeted method. In total, 82 baseline plasma samples (41 insufficient responders and 41 sufficient responders to MTX) were selected from the Treatment in [...] Read more.
This study aimed to identify baseline metabolic biomarkers for response to methotrexate (MTX) therapy in rheumatoid arthritis (RA) using an untargeted method. In total, 82 baseline plasma samples (41 insufficient responders and 41 sufficient responders to MTX) were selected from the Treatment in the Rotterdam Early Arthritis Cohort (tREACH, trial number: ISRCTN26791028) based on patients’ EULAR response at 3 months. Metabolites were assessed using high-performance liquid chromatography-quadrupole time of flight mass spectrometry. Differences in metabolite concentrations between insufficient and sufficient responders were assessed using partial least square regression discriminant analysis (PLS-DA) and Welch’s t-test. The predictive performance of the most significant findings was assessed in a receiver operating characteristic plot with area under the curve (AUC), sensitivity and specificity. Finally, overrepresentation analysis was performed to assess if the best discriminating metabolites were enriched in specific metabolic events. Baseline concentrations of homocystine, taurine, adenosine triphosphate, guanosine diphosphate and uric acid were significantly lower in plasma of insufficient responders versus sufficient responders, while glycolytic intermediates 1,3-/2,3-diphosphoglyceric acid, glycerol-3-phosphate and phosphoenolpyruvate were significantly higher in insufficient responders. Homocystine, glycerol-3-phosphate and 1,3-/2,3-diphosphoglyceric acid were independent predictors and together showed a high AUC of 0.81 (95% CI: 0.72–0.91) for the prediction of insufficient response, with corresponding sensitivity of 0.78 and specificity of 0.76. The Warburg effect, glycolysis and amino acid metabolism were identified as underlying metabolic events playing a role in clinical response to MTX in early RA. New metabolites and potential underlying metabolic events correlating with MTX response in early RA were identified, which warrant validation in external cohorts. Full article
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13 pages, 767 KiB  
Article
Equivocal PI-RADS Three Lesions on Prostate Magnetic Resonance Imaging: Risk Stratification Strategies to Avoid MRI-Targeted Biopsies
by Daniël F. Osses, Christian Arsov, Lars Schimmöller, Ivo G. Schoots, Geert J.L.H. van Leenders, Irene Esposito, Sebastiaan Remmers, Peter Albers and Monique J. Roobol
J. Pers. Med. 2020, 10(4), 270; https://doi.org/10.3390/jpm10040270 - 10 Dec 2020
Cited by 7 | Viewed by 6286
Abstract
We aimed to investigate the relation between largest lesion diameter, prostate-specific antigen density (PSA-D), age, and the detection of clinically significant prostate cancer (csPCa) using first-time targeted biopsy (TBx) in men with Prostate Imaging—Reporting and Data System (PI-RADS) 3 index lesions. A total [...] Read more.
We aimed to investigate the relation between largest lesion diameter, prostate-specific antigen density (PSA-D), age, and the detection of clinically significant prostate cancer (csPCa) using first-time targeted biopsy (TBx) in men with Prostate Imaging—Reporting and Data System (PI-RADS) 3 index lesions. A total of 292 men (2013–2019) from two referral centers were included. A multivariable logistic regression analysis was performed. The discrimination and clinical utility of the built model was assessed by the area under the receiver operation curve (AUC) and decision curve analysis, respectively. A higher PSA-D and higher age were significantly related to a higher risk of detecting csPCa, while the largest index lesion diameter was not. The discrimination of the model was 0.80 (95% CI 0.73–0.87). When compared to a biopsy-all strategy, decision curve analysis showed a higher net benefit at threshold probabilities of ≥2%. Accepting a missing ≤5% of csPCa diagnoses, a risk-based approach would result in 34% of TBx sessions and 23% of low-risk PCa diagnoses being avoided. In men with PI-RADS 3 index lesions scheduled for first-time TBx, the balance between the number of TBx sessions, the detection of low-risk PCa, and the detection of csPCa does not warrant a biopsy-all strategy. To minimize the risk of missing the diagnosis of csPCa but acknowledging the need of avoiding unnecessary TBx sessions and overdiagnosis, a risk-based approach is advisable. Full article
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16 pages, 3462 KiB  
Article
Pulmonary Manifestations of Plasma Cell Type Idiopathic Multicentric Castleman Disease: A Clinicopathological Study in Comparison with IgG4-Related Disease
by Midori Filiz Nishimura, Takuro Igawa, Yuka Gion, Sakura Tomita, Dai Inoue, Akira Izumozaki, Yoshifumi Ubara, Yoshito Nishimura, Tadashi Yoshino and Yasuharu Sato
J. Pers. Med. 2020, 10(4), 269; https://doi.org/10.3390/jpm10040269 - 10 Dec 2020
Cited by 16 | Viewed by 3412
Abstract
Plasma cell type idiopathic multicentric Castleman disease (PC-iMCD) occasionally manifests as parenchymal lung disease. This study aimed to elucidate the detailed clinicopathological features of lung lesions in PC-iMCD and compare the findings with those in immunoglobulin (Ig) G4-related disease (IgG4-RD), the most difficult [...] Read more.
Plasma cell type idiopathic multicentric Castleman disease (PC-iMCD) occasionally manifests as parenchymal lung disease. This study aimed to elucidate the detailed clinicopathological features of lung lesions in PC-iMCD and compare the findings with those in immunoglobulin (Ig) G4-related disease (IgG4-RD), the most difficult differential diagnosis of PC-iMCD. We analyzed the clinicopathological findings and immunohistochemical expression patterns of interleukin-6 (IL-6) and Igs in lung specimens from 16 patients with PC-iMCD and 7 patients with IgG4-RD. Histologically, pulmonary PC-iMCD could not be differentiated from IgG4-RD based on lesion distribution patterns, the number of lymphoid follicles and obliterative vasculitis, or fibrosis types. The eosinophil count was higher in the IgG4-RD group than in the PC-iMCD group (p = 0.004). The IgG4/IgG-positive cell ratio was significantly higher in the IgG4-RD group (p < 0.001). The IgA-positive cell count and IL-6 expression intensity were higher in the PC-iMCD group than in the IgG4-RD group (p < 0.001). Based on these findings, we proposed a new diagnostic approach to differentiate lung lesions of PC-iMCD and IgG4-RD. Our approach can be utilized to stratify patients with suspected lung-dominant PC-iMCD to identify candidates for strong immunosuppressive treatment, including IL-6 blockade, at an early stage. Full article
(This article belongs to the Section Mechanisms of Diseases)
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10 pages, 456 KiB  
Article
Does Transfusion of Red Blood Cells Impact Germline Genetic Test Results?
by Maggie A. DiGuardo, Sarah J. Kester, Victor J. Mahaffey, Scott A. Hammel, Katelyn K. Heaser, Christopher D. Hofich, Craig D. Tauscher, Sarah E. Kerr, Jennifer L. Oliveira, Eapen K. Jacob and Ann M. Moyer
J. Pers. Med. 2020, 10(4), 268; https://doi.org/10.3390/jpm10040268 - 09 Dec 2020
Cited by 3 | Viewed by 2235
Abstract
Purpose: molecular testing is often indicated for recently transfused patients. However, there are no guidelines regarding the potential interference from donor DNA or whether it is necessary to wait for a period of time post-transfusion prior to genetic testing. While the majority of [...] Read more.
Purpose: molecular testing is often indicated for recently transfused patients. However, there are no guidelines regarding the potential interference from donor DNA or whether it is necessary to wait for a period of time post-transfusion prior to genetic testing. While the majority of patients are transfused in the non-trauma setting using leukoreduced (LR) red blood cell products, the degree of leukoreduction varies among centers and is not universally practiced. Methods: whole blood units collected from anonymous donors were used in an in vitro transfusion model. One unit was split: half being leukoreduced simulating a leukopenic recipient and half left untreated. Donors were simulated by leukoreduced, partially leukoreduced (PLR), or non-leukoreduced units, transfused in 2, 5, or 16 unit equivalents. DNA from the combinations were subjected to short tandem repeat (STR) analysis for chimerism detection. Results: donor DNA was not detectable in any of the LR combinations, but detected in the PLR combinations, ranging from 0.1 to 1.5% donor DNA in the immunocompetent recipient and 6.3–27.8% in the leukopenic recipient. Non-LR donor DNA was also detected (13–95%). Conclusion: donor-derived DNA from leukoreduced blood products is unlikely to interfere with the interpretation of germline genetic testing in immunocompetent recipients but may interfere in immunocompromised recipients. Full article
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17 pages, 276 KiB  
Article
Genomic Association of Single Nucleotide Polymorphisms with Blood Pressure Response to Hydrochlorothiazide among South African Adults with Hypertension
by Charity Masilela, Brendon Pearce, Joven Jebio Ongole, Oladele Vincent Adeniyi and Mongi Benjeddou
J. Pers. Med. 2020, 10(4), 267; https://doi.org/10.3390/jpm10040267 - 09 Dec 2020
Cited by 2 | Viewed by 2204
Abstract
This study described single nucleotide polymorphisms (SNPs) in hydrochlorothiazide-associated genes and further assessed their correlation with blood pressure control among South African adults living with hypertension. A total of 291 participants belonging to the Nguni tribes of South Africa on treatment for hypertension [...] Read more.
This study described single nucleotide polymorphisms (SNPs) in hydrochlorothiazide-associated genes and further assessed their correlation with blood pressure control among South African adults living with hypertension. A total of 291 participants belonging to the Nguni tribes of South Africa on treatment for hypertension were recruited. Nineteen SNPs in hydrochlorothiazide pharmacogenes were selected and genotyped using MassArray. Uncontrolled hypertension was defined as blood pressure ≥140/90 mmHg. The association between genotypes, alleles and blood pressure response to treatment was determined by conducting multivariate logistic regression model analysis. The majority of the study participants were female (73.19%), Xhosa (54.98%) and had blood pressure ≥140/90 mmHg (68.73%). Seventeen SNPs were observed among the Xhosa tribe, and two (rs2070744 and rs7297610) were detected among Swati and Zulu participants. Furthermore, alleles T of rs2107614 (AOR = 6.69; 95%CI 1.42–31.55; p = 0.016) and C of rs2776546 (AOR = 3.78; 95%CI 1.04–13.74; p = 0.043) were independently associated with uncontrolled hypertension, whilst rs2070744 TC (AOR = 38.76; 95%CI 5.54–270.76; p = 0.00023), CC (AOR = 10.44; 95%CI 2.16–50.29; p = 0.003) and allele T of rs7297610 (AOR = 1.86; 95%CI 1.09–3.14; p = 0.023) were significantly associated with uncontrolled hypertension among Zulu and Swati participants. We confirmed the presence of SNPs associated with hydrochlorothiazide, some of which were significantly associated with uncontrolled hypertension in the study sample. Findings open doors for further studies on personalized therapy for hypertension in the country. Full article
(This article belongs to the Section Pharmacogenetics)
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20 pages, 1869 KiB  
Article
A Multi-mRNA Host-Response Molecular Blood Test for the Diagnosis and Prognosis of Acute Infections and Sepsis: Proceedings from a Clinical Advisory Panel
by James Ducharme, Wesley H. Self, Tiffany M. Osborn, Nathan A. Ledeboer, Jonathan Romanowsky, Timothy E. Sweeney, Oliver Liesenfeld and Richard E. Rothman
J. Pers. Med. 2020, 10(4), 266; https://doi.org/10.3390/jpm10040266 - 07 Dec 2020
Cited by 27 | Viewed by 5058
Abstract
Current diagnostics are insufficient for diagnosis and prognosis of acute infections and sepsis. Clinical decisions including prescription and timing of antibiotics, ordering of additional diagnostics and level-of-care decisions rely on understanding etiology and implications of a clinical presentation. Host mRNA signatures can differentiate [...] Read more.
Current diagnostics are insufficient for diagnosis and prognosis of acute infections and sepsis. Clinical decisions including prescription and timing of antibiotics, ordering of additional diagnostics and level-of-care decisions rely on understanding etiology and implications of a clinical presentation. Host mRNA signatures can differentiate infectious from noninfectious etiologies, bacterial from viral infections, and predict 30-day mortality. The 29-host-mRNA blood-based InSepTM test (Inflammatix, Burlingame, CA, formerly known as HostDxTM Sepsis) combines machine learning algorithms with a rapid point-of-care platform with less than 30 min turnaround time to enable rapid diagnosis of acute infections and sepsis, as well as prediction of disease severity. A scientific advisory panel including emergency medicine, infectious disease, intensive care and clinical pathology physicians discussed technical and clinical requirements in preparation of successful introduction of InSep into the market. Topics included intended use; patient populations of greatest need; patient journey and sample flow in the emergency department (ED) and beyond; clinical and biomarker-based decision algorithms; performance characteristics for clinical utility; assay and instrument requirements; and result readouts. The panel identified clear demand for a solution like InSep, requirements regarding test performance and interpretability, and a need for focused medical education due to the innovative but complex nature of the result readout. Innovative diagnostic solutions such as the InSep test could improve management of patients with suspected acute infections and sepsis in the ED, thereby lessening the overall burden of these conditions on patients and the healthcare system. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Patients with Sepsis)
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9 pages, 245 KiB  
Article
Oligometastatic Prostate Adenocarcinoma. Clinical-Pathologic Study of a Histologically Under-Recognized Prostate Cancer
by Claudia Manini, Alba González, David Büchser, Jorge García-Olaverri, Arantza Urresola, Ana Ezquerro, Iratxe Fernández, Roberto Llarena, Iñaki Zabalza, Rafael Pulido, Arkaitz Carracedo, Alfonso Gómez-Iturriaga and José I. López
J. Pers. Med. 2020, 10(4), 265; https://doi.org/10.3390/jpm10040265 - 04 Dec 2020
Cited by 3 | Viewed by 2052
Abstract
The clinical parameters and the histological and immunohistochemical findings of a prospective protocolized series of 27 prostate carcinoma patients with oligometastatic disease followed homogeneously were analyzed. Lymph nodes (81.5%) and bones (18.5%) were the only metastatic sites. Local control after metastatic directed treatment [...] Read more.
The clinical parameters and the histological and immunohistochemical findings of a prospective protocolized series of 27 prostate carcinoma patients with oligometastatic disease followed homogeneously were analyzed. Lymph nodes (81.5%) and bones (18.5%) were the only metastatic sites. Local control after metastatic directed treatment was achieved in 22 (81.5%) patients. A total of 8 (29.6%) patients developed castration-resistant prostate cancer. Seventeen (63%) patients presented with non-organ confined disease. The Gleason index 8–10 was the most frequently observed (12 cases, 44.4%) combined grade. Positive immunostainings were detected with androgen receptor (100%), PGP 9.5 (74%), ERG (40.7%), chromogranin A (29.6%), and synaptophysin (18.5%) antibodies. The Ki-67 index value > 5% was observed in 15% of the cases. L1CAM immunostaining was negative in all cases. Fisher exact test showed that successful local control of metastases was associated to mild inflammation, organ confined disease, Ki-67 index < 5%, and Gleason index 3 + 3. A castration resistant status was associated with severe inflammation, atrophy, a Gleason index higher than 3 + 3, Ki-67 index ≥ 5%, and positive PGP 9.5, chromogranin A, and synaptophysin immunostainings. In conclusion, oligometastatic prostate adenocarcinoma does not have a specific clinical-pathologic profile. However, some histologic and immunohistochemical parameters of routine use may help with making therapeutic decisions. Full article
(This article belongs to the Special Issue Stereotactic Body Radiotherapy)
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