Journal of Personalized Medicine

14 pages, 3066 KiB

Open AccessArticle

Discovering Breast Cancer Biomarkers Candidates through mRNA Expression Analysis Based on The Cancer Genome Atlas Database

by Dong Hyeok Kim and Kyung Eun Lee

J. Pers. Med. 2022, 12(10), 1753; https://doi.org/10.3390/jpm12101753 - 21 Oct 2022

Cited by 3 | Viewed by 2131

Abstract

Background: Research on the discovery of tumor biomarkers based on big data analysis is actively being conducted. This study aimed to secure foundational data for identifying new biomarkers of breast cancer via breast cancer datasets in The Cancer Genome Atlas (TCGA). Methods: The [...] Read more.

Background: Research on the discovery of tumor biomarkers based on big data analysis is actively being conducted. This study aimed to secure foundational data for identifying new biomarkers of breast cancer via breast cancer datasets in The Cancer Genome Atlas (TCGA). Methods: The mRNA profiles of 526 breast cancer and 60 adjacent non-cancerous breast tissues collected from TCGA datasets were analyzed via MultiExperiment Viewer and GraphPad Prism. Diagnostic performance was analyzed by identifying the pathological grades of the selected differentially expressed (DE) mRNAs and the expression patterns of molecular subtypes. Results: Via DE mRNA profile analysis, we selected 14 mRNAs with downregulated expression (HADH, CPN2, ADAM33, TDRD10, SNF1LK2, HBA2, KCNIP2, EPB42, PYGM, CEP68, ING3, EMCN, SYF2, and DTWD1) and six mRNAs with upregulated expression (ZNF8, TOMM40, EVPL, EPN3, AP1M2, and SPINT2) in breast cancer tissues compared to that in non-cancerous tissues (p < 0.001). Conclusions: In total, 20 DE mRNAs had an area under cover of 0.9 or higher, demonstrating excellent diagnostic performance in breast cancer. Therefore, the results of this study will provide foundational data for planning preliminary studies to identify new tumor biomarkers. Full article

(This article belongs to the Special Issue New Advances in Clinical and Translational Breast Cancer Research)

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Graphical abstract

12 pages, 293 KiB

Open AccessReview

Combined Assay of rDNA and SatIII Copy Numbers as an Individual Profile of Stress Resistance, Longevity, Fertility and Disease Predisposition

by Lev N. Porokhovnik

J. Pers. Med. 2022, 12(10), 1752; https://doi.org/10.3390/jpm12101752 - 21 Oct 2022

Viewed by 1121

Abstract

The ribosomal DNA and pericentromeric satellite repeats are two important types of moderately repeated sequences existing in the human genome. They are functionally involved in the universal stress response. There is accumulating evidence that the copy number variation (CNV) of the repeat units [...] Read more.

The ribosomal DNA and pericentromeric satellite repeats are two important types of moderately repeated sequences existing in the human genome. They are functionally involved in the universal stress response. There is accumulating evidence that the copy number variation (CNV) of the repeat units is a novel factor modulating the stress response and, thus, has phenotypic manifestations. The ribosomal repeat copy number plays a role in stress resistance, lifespan, in vitro fertilization chances, disease progression and aging, while the dynamics of the satellite copy number are a sort of indicator of the current stress state. Here, we review some facts showing that a combined assay of rDNA and SatII/III abundance can provide valuable individual data (“stress profile”) indicating not only the inherited adaptive reserve but also the stress duration and acute or chronic character of the stress. Thus, the repeat count could have applications in personalized medicine in the future. Full article

(This article belongs to the Special Issue From Prediction to Diagnosis: The Application of Genomics in Personalized Medicine)

11 pages, 272 KiB

Open AccessArticle

Satisfaction with Surgical Procedures and Bladder Management of Chronic Spinal Cord Injured Patients with Voiding Dysfunction Who Desire Spontaneous Voiding

by Shu-Yu Wu and Hann-Chorng Kuo

J. Pers. Med. 2022, 12(10), 1751; https://doi.org/10.3390/jpm12101751 - 21 Oct 2022

Cited by 6 | Viewed by 1229

Abstract

We aimed to investigate treatment outcome and satisfaction with bladder outlet surgeries and bladder management in patients with spinal cord injury (SCI), voiding dysfunction, and to seek a spontaneous voiding or reflex voiding program. A total of 261 patients were included in this [...] Read more.

We aimed to investigate treatment outcome and satisfaction with bladder outlet surgeries and bladder management in patients with spinal cord injury (SCI), voiding dysfunction, and to seek a spontaneous voiding or reflex voiding program. A total of 261 patients were included in this retrospective study. The mean age at surgical procedure was 49.2 ± 15.9 years; the median follow-up period was 11 (IQR 6, 17) years; 119 received a urethral Botox injection, 41 underwent transurethral incision of the bladder neck (TUI-BN), 77 underwent transurethral incision or resection of the prostate (TUI-P or TUR-P), and 24 had an external sphincterotomy. Satisfactory surgical outcome was reported by 80.5% of patients undergoing TUI-BN, 70.8% undergoing external sphincterotomy, 64.9% receiving TUI-P or TUR-P, and 59.7% receiving the urethral Botox injection. Persistent dysuria was the most common reason for dissatisfaction after the urethral Botox injection (73.1%) and TUI-BN (58.5%). Recurrent urinary tract infection continued in most patients after any type of surgery (all >75%). Most patients with SCI were satisfied with their initial bladder outlet operation in facilitating spontaneous voiding. However, repeat, or multiple surgical interventions were needed in 65.5% of SCI patients to achieve satisfactory voiding. A correct diagnosis is very important before every intervention and bladder management to reach the best satisfaction. VUDS is suggested before surgical procedures to ensure efficacy, even in patients with the same level of SCI. Full article

(This article belongs to the Topic Clinical, Translational, Basic Researches, and Application of Bacterial Toxins on Bladder Diseases and Lower Urinary Tract Dysfunctions)

13 pages, 3663 KiB

Open AccessArticle

Analysis of MicroRNA Regulation and Gene Expression Variability in Single Cell Data

by Wendao Liu and Noam Shomron

J. Pers. Med. 2022, 12(10), 1750; https://doi.org/10.3390/jpm12101750 - 21 Oct 2022

Viewed by 1440

Abstract

MicroRNAs (miRNAs) regulate gene expression by binding to mRNAs, and thus reduce target gene expression levels and expression variability, also known as ‘noise’. Single-cell RNA sequencing (scRNA-seq) technology has been used to study miRNA and mRNA expression in single cells. To evaluate scRNA-seq [...] Read more.

MicroRNAs (miRNAs) regulate gene expression by binding to mRNAs, and thus reduce target gene expression levels and expression variability, also known as ‘noise’. Single-cell RNA sequencing (scRNA-seq) technology has been used to study miRNA and mRNA expression in single cells. To evaluate scRNA-seq as a tool for investigating miRNA regulation, we analyzed datasets with both mRNA and miRNA expression in single-cell format. We found that miRNAs slightly reduce the expression noise of target genes; however, this effect is easily masked by strong technical noise from scRNA-seq. We suggest improvements aimed at reducing technical noise, which can be implemented in experimental design and computational analysis prior to running scRNA-seq. Our study provides useful guidelines for experiments that evaluate the effect of miRNAs on mRNA expression from scRNA-seq. Full article

(This article belongs to the Special Issue Use of Single-Cell Omics in Personalized Medicine)

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12 pages, 899 KiB

Open AccessArticle

Investigation of Different Methods of Intraoperative Graft Perfusion Assessment during Kidney Transplantation for the Prediction of Delayed Graft Function: A Prospective Pilot Trial

by Andreas L. H. Gerken, Michael Keese, Christel Weiss, Hanna-Sophie Krücken, Katarina A. P. Pecher, Augusto Ministro, Nuh N. Rahbari, Christoph Reissfelder, Ulrich Rother, Babak Yazdani, Anna-Isabelle Kälsch, Bernhard K. Krämer and Kay Schwenke

J. Pers. Med. 2022, 12(10), 1749; https://doi.org/10.3390/jpm12101749 - 21 Oct 2022

Cited by 1 | Viewed by 1376

Abstract

Delayed graft function (DGF) after renal transplantation is a relevant clinical problem affecting long-term organ function. The early detection of patients at risk is crucial for postoperative monitoring and treatment algorithms. In this prospective cohort study, allograft perfusion was evaluated intraoperatively in 26 [...] Read more.

Delayed graft function (DGF) after renal transplantation is a relevant clinical problem affecting long-term organ function. The early detection of patients at risk is crucial for postoperative monitoring and treatment algorithms. In this prospective cohort study, allograft perfusion was evaluated intraoperatively in 26 kidney recipients by visual and formal perfusion assessment, duplex sonography, and quantitative microperfusion assessment using O2C spectrometry and ICG fluorescence angiography. The O2C tissue spectrometry device provides a quantitative method of microperfusion assessment that can be employed during kidney transplantation as an easy-to-use and highly sensitive alternative to ICG fluorescence angiography. Intraoperative microvascular flow and velocity in the allograft cortex after reperfusion predicted DGF with a sensitivity of 100% and a specificity of 82%. Threshold values of 57 A.U. for microvascular flow and 13 A.U. for microvascular velocity were identified by an ROC analysis. This study, therefore, confirmed that impairment of microperfusion of the allograft cortex directly after reperfusion was a key indicator for the occurrence of DGF after kidney transplantation. Our results support the combined use of intraoperative duplex sonography, for macrovascular quality control, and quantitative microperfusion assessment, such as O2C spectrometry, for individual risk stratification to guide subsequent postoperative management. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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9 pages, 3434 KiB

Open AccessArticle

Entry Point Variation in the Osseous Fixation Pathway of the Anterior Column of the Pelvis—A Three-Dimensional Analysis

by Lotte Dupuis, Laura A. van Ginkel, Luc M. Verhamme, Thomas J. J. Maal, Erik Hermans and Vincent M. A. Stirler

J. Pers. Med. 2022, 12(10), 1748; https://doi.org/10.3390/jpm12101748 - 21 Oct 2022

Cited by 1 | Viewed by 1545

Abstract

Fractures of the superior pubic ramus can be treated with screw insertion into the osseous fixation pathway (OFP) of the anterior column (AC). The entry point determines whether the screw exits the OFP prematurely. This can be harmful when it enters the hip [...] Read more.

Fractures of the superior pubic ramus can be treated with screw insertion into the osseous fixation pathway (OFP) of the anterior column (AC). The entry point determines whether the screw exits the OFP prematurely. This can be harmful when it enters the hip joint or damages soft tissues inside the lesser pelvis. The exact entry point varies between patients and can be difficult to ascertain on fluoroscopy during surgery. The aim of this study was to determine variation in the location of the entry point. A retrospective single center study was performed at a level 1 trauma center in the Netherlands. Nineteen adult patients were included with an undisplaced fracture of the superior pubic ramus on computer tomography (CT)-scan. Virtual three-dimensional (3D) models of the pelvises were created. Multiple screws were placed per AC and the models were superimposed. A total of 157 screws were placed, of which 109 did not exit the OFP prematurely. A universally reproducible entry point could not be identified. A typical crescent shaped region of entry points did exist and was located more laterally in females when compared to males. Three-dimensional virtual surgery planning can be helpful to identify the ideal entry points in each case. Full article

(This article belongs to the Topic Complex Systems and Artificial Intelligence)

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12 pages, 2297 KiB

Open AccessArticle

Cerebrospinal Fluid Biomarker Profile in TDP-43-Related Genetic Frontotemporal Dementia

by Elisabeth Kapaki, Foteini Boufidou, Mara Bourbouli, Efstratios-Stylianos Pyrgelis, Vasilios C. Constantinides, Cleo Anastassopoulou and George P. Paraskevas

J. Pers. Med. 2022, 12(10), 1747; https://doi.org/10.3390/jpm12101747 - 21 Oct 2022

Cited by 3 | Viewed by 2105

Abstract

Cerebrospinal fluid (CSF) biomarkers, namely total tau, phospho-tau and amyloid beta peptides, have received much attention specifically regarding Alzheimer’s disease (AD), since they can detect the biochemical fingerprint of AD and serve as a diagnostic tool for accurate and early diagnosis during life. [...] Read more.

Cerebrospinal fluid (CSF) biomarkers, namely total tau, phospho-tau and amyloid beta peptides, have received much attention specifically regarding Alzheimer’s disease (AD), since they can detect the biochemical fingerprint of AD and serve as a diagnostic tool for accurate and early diagnosis during life. In the same way, biomarkers for other neurodegenerative disease pathologies are also needed. We present a case series of six patients with genetic frontotemporal dementia (FTD), with TDP-43 underlying proteinopathy, in an attempt to assess TDP-43 as a novel biomarker alone and in combination with established AD biomarkers for this specific patient group, based on the principles of personalized and precision medicine. Our results indicate that genetic TDP-43-FTD is characterized by increased CSF TPD-43 and increased TDP-43 × τ_Τ/τ_P-181 combination. Hence, TDP-43 combined with tau proteins could be a useful tool for the diagnosis of genetic FTD with TDP-43 underling histopathology, supplementing clinical, neuropsychological and imaging data. Full article

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12 pages, 629 KiB

Open AccessCommentary

Integrating a Comprehensive Cancer Genome Profiling into Clinical Practice: A Blueprint in an Italian Referral Center

by Camilla Nero, Simona Duranti, Flavia Giacomini, Angelo Minucci, Luciano Giacò, Alessia Piermattei, Maurizio Genuardi, Tina Pasciuto, Andrea Urbani, Gennaro Daniele, Domenica Lorusso, Raffaele Pignataro, Giampaolo Tortora, Nicola Normanno and Giovanni Scambia

J. Pers. Med. 2022, 12(10), 1746; https://doi.org/10.3390/jpm12101746 - 20 Oct 2022

Cited by 5 | Viewed by 2757

Abstract

The implementation of cancer molecular characterization in clinical practice has improved prognostic re-definition, extending the eligibility to a continuously increasing number of targeted treatments. Broad molecular profiling technologies better than organ-based approaches are believed to serve such dynamic purposes. We here present the [...] Read more.

The implementation of cancer molecular characterization in clinical practice has improved prognostic re-definition, extending the eligibility to a continuously increasing number of targeted treatments. Broad molecular profiling technologies better than organ-based approaches are believed to serve such dynamic purposes. We here present the workflow our institution adopted to run a comprehensive cancer genome profiling in clinical practice. This article describes the workflow designed to make a comprehensive cancer genome profiling program feasible and sustainable in a large-volume referral hospital. Full article

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13 pages, 724 KiB

Open AccessEditor’s ChoiceReview

Advanced Bladder Cancer: Changing the Treatment Landscape

by Vladimir Bilim, Hiroo Kuroki, Yuko Shirono, Masaki Murata, Kaede Hiruma and Yoshihiko Tomita

J. Pers. Med. 2022, 12(10), 1745; https://doi.org/10.3390/jpm12101745 - 20 Oct 2022

Cited by 14 | Viewed by 3100

Abstract

Bladder cancer is the 10th most common cancer type in the world. There were more than 573,000 new cases of bladder cancer in 2020. It is the 13th most common cause of cancer death with an estimated more than 212,000 deaths worldwide. Low-grade [...] Read more.

Bladder cancer is the 10th most common cancer type in the world. There were more than 573,000 new cases of bladder cancer in 2020. It is the 13th most common cause of cancer death with an estimated more than 212,000 deaths worldwide. Low-grade non-muscle-invasive bladder cancer (NMIBC) is usually successfully managed with transurethral resection (TUR) and overall survival for NMIBC reaches 90% according to some reports. However, long-term survival for muscle-invasive bladder cancer (MIBC) and metastatic bladder cancer remains low. Treatment options for bladder cancer have undergone a rapid change in recent years. Immune checkpoint inhibitors (ICI), targeted therapies, and antibody-drug conjugates are available now. As bladder cancer is genetically heterogeneous, the optimization of patient selection to identify those most likely to benefit from a specific therapy is an urgent issue in the treatment of patients with bladder cancer. Full article

(This article belongs to the Section Mechanisms of Diseases)

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10 pages, 759 KiB

Open AccessArticle

Influence of Renal Impairment on the Success of Reconstruction Using Microvascular Grafts—A Retrospective Study of 251 Free Flaps

by Henriette L. Moellmann, Nadia Karnatz, Ilkan Degirmenci, Antonina Gyurova, Lorenz Sellin and Majeed Rana

J. Pers. Med. 2022, 12(10), 1744; https://doi.org/10.3390/jpm12101744 - 20 Oct 2022

Viewed by 1134

Abstract

Background: In head and neck surgery, reconstruction using microvascular grafts is a successful method for functional and aesthetic restoration. Due to technological advances and medical care, the number of patients with comorbidities and diseases requiring free tissue transfer has increased. To provide adequate [...] Read more.

Background: In head and neck surgery, reconstruction using microvascular grafts is a successful method for functional and aesthetic restoration. Due to technological advances and medical care, the number of patients with comorbidities and diseases requiring free tissue transfer has increased. To provide adequate treatment to these patients, preoperative identification of potential risk factors is essential. Methods: In this retrospective study, we investigated the impact of renal insufficiency on reconstruction in 251 microvascular grafts. Perioperative complications, failure rate, and outcomes serve as the basis for this evaluation. Results: Comparing pre- and postoperative values, there was a significant decrease in potassium and creatinine levels and a significant increase in GFR. The electrolyte changes in relation to the complication rate showed that complications were more likely to occur as potassium levels increased. As sodium levels increase, the complication rate decreases. Conclusion: A preoperative value indicative of impaired renal function, such as creatinine levels, GFR, or electrolytes, did not prove to be an individual risk factor for the occurrence of graft failure in this patient population. Nevertheless, increased renal parameters are associated with increased incidence of serious complications. Therefore, these should be considered in the indication and preoperative planning. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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21 pages, 707 KiB

Open AccessReview

Next-Generation Examination, Diagnosis, and Personalized Medicine in Periodontal Disease

by Takeshi Kikuchi, Jun-ichiro Hayashi and Akio Mitani

J. Pers. Med. 2022, 12(10), 1743; https://doi.org/10.3390/jpm12101743 - 20 Oct 2022

Cited by 6 | Viewed by 2449

Abstract

Periodontal disease, a major cause of tooth loss, is an infectious disease caused by bacteria with the additional aspect of being a noncommunicable disease closely related to lifestyle. Tissue destruction based on chronic inflammation is influenced by host and environmental factors. The treatment [...] Read more.

Periodontal disease, a major cause of tooth loss, is an infectious disease caused by bacteria with the additional aspect of being a noncommunicable disease closely related to lifestyle. Tissue destruction based on chronic inflammation is influenced by host and environmental factors. The treatment of periodontal disease varies according to the condition of each individual patient. Although guidelines provide standardized treatment, optimization is difficult because of the wide range of treatment options and variations in the ideas and skills of the treating practitioner. The new medical concepts of “precision medicine” and “personalized medicine” can provide more predictive treatment than conventional methods by stratifying patients in detail and prescribing treatment methods accordingly. This requires a new diagnostic system that integrates information on individual patient backgrounds (biomarkers, genetics, environment, and lifestyle) with conventional medical examination information. Currently, various biomarkers and other new examination indices are being investigated, and studies on periodontal disease-related genes and the complexity of oral bacteria are underway. This review discusses the possibilities and future challenges of precision periodontics and describes the new generation of laboratory methods and advanced periodontal disease treatment approaches as the basis for this new field. Full article

(This article belongs to the Special Issue Precision Medicine for Oral Diseases)

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23 pages, 519 KiB

Open AccessSystematic Review

Biological Predictors of Treatment Response in Adult Attention Deficit Hyperactivity Disorder (ADHD): A Systematic Review

by Enrico Capuzzi, Alice Caldiroli, Anna Maria Auxilia, Riccardo Borgonovo, Martina Capellazzi, Massimo Clerici and Massimiliano Buoli

J. Pers. Med. 2022, 12(10), 1742; https://doi.org/10.3390/jpm12101742 - 20 Oct 2022

Viewed by 1947

Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent condition with onset in childhood and in many cases persisting into adulthood. Even though an increasing number of studies have investigated the efficacy of pharmacotherapy in the management of adult ADHD, few authors have tried [...] Read more.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent condition with onset in childhood and in many cases persisting into adulthood. Even though an increasing number of studies have investigated the efficacy of pharmacotherapy in the management of adult ADHD, few authors have tried to identify the biological predictors of treatment response. Objectives: To summarize the available data about the biological markers of treatment response in adults affected by ADHD. Methods: A search on the main biomedical and psychological archives (PubMed, Embase, Scopus, and PsycINFO) was performed. Manuscripts in English, published up to May 2022 and having the biological predictors of treatment response in adults with ADHD as their main topic, were included. Results: A total of 3855 articles was screened. Twenty-two articles were finally included. Most of the manuscripts studied neuroimaging and electrophysiological factors as potential predictors of treatment response in adult ADHD patients. No reliable markers were identified until now. Promising findings on this topic regard genetic polymorphisms in snap receptor (SNARE) proteins and default mode network-striatum connectivity. Conclusions: Even though some biological markers seem promising for the prediction of treatment response in adults affected by ADHD, further studies are needed to confirm the available data in the context of precision medicine. Full article

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9 pages, 2075 KiB

Open AccessArticle

A Preliminary Study of Interdisciplinary Approach with a Single-Stage Surgery in Children with Cleft Lip and Palate

by Takashi Matsumura, Hitoshi Kawanabe, Naoko Nemoto, Saki Ogino, Kazunori Fukui, Akihiko Oyama and Toru Okamoto

J. Pers. Med. 2022, 12(10), 1741; https://doi.org/10.3390/jpm12101741 - 20 Oct 2022

Cited by 1 | Viewed by 1953

Abstract

A two-stage surgical procedure involving labioplasty and palatoplasty is a common surgical modality performed in children with cleft lip and palate. Additionally, an alveolar cleft bone graft is performed prior to the eruption of the canine teeth. These three surgeries impose the burden [...] Read more.

A two-stage surgical procedure involving labioplasty and palatoplasty is a common surgical modality performed in children with cleft lip and palate. Additionally, an alveolar cleft bone graft is performed prior to the eruption of the canine teeth. These three surgeries impose the burden of general anesthesia separately for each procedure, and the formation of scar tissue from the procedure inhibits maxillary growth. We adopted a single-stage surgical procedure to overcome these drawbacks. To date, there have been no reports comparing the treatment outcomes of alveolar morphology and maxillary growth and development in children who underwent single-stage surgery with those who underwent two-stage surgery using plaster casts and cephalograms. Twenty children aged 5–7 years were equally divided into two groups based on whether they had undergone a two- or single-stage procedure. Cephalometric analysis and analysis of dentition models were conducted. The results showed that the single-stage surgery exhibited significant differences in the sella-nasion angle, point A to McNamara line, maxillary length, mandibular body length, and posterior arch width and length compared with the two-stage surgery. Therefore, it was suggested that the single-stage surgery had a favorable effect on maxillary growth compared with the two-stage surgery. Full article

(This article belongs to the Special Issue Precision Medicine for Oral Diseases)

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13 pages, 1110 KiB

Open AccessArticle

Relatives from Hereditary Breast and Ovarian Cancer and Lynch Syndrome Families Forgoing Genetic Testing: Findings from the Swiss CASCADE Cohort

by Mahesh Sarki, Chang Ming, Monica Aceti, Günther Fink, Souria Aissaoui, Nicole Bürki, Rossella Graffeo, Karl Heinimann, Maria Caiata Zufferey, Christian Monnerat, Manuela Rabaglio, Ursina Zürrer-Härdi, Pierre O. Chappuis, Maria C. Katapodi and the CASCADE Consortium

J. Pers. Med. 2022, 12(10), 1740; https://doi.org/10.3390/jpm12101740 - 19 Oct 2022

Cited by 6 | Viewed by 2338

Abstract

Cascade genetic testing of relatives from families with pathogenic variants associated with hereditary breast and ovarian cancer (HBOC) or Lynch syndrome (LS) has important implications for cancer prevention. We compared the characteristics of relatives from HBOC or LS families who did not have [...] Read more.

Cascade genetic testing of relatives from families with pathogenic variants associated with hereditary breast and ovarian cancer (HBOC) or Lynch syndrome (LS) has important implications for cancer prevention. We compared the characteristics of relatives from HBOC or LS families who did not have genetic testing (GT (−) group) with those who had genetic testing (GT (+) group), regardless of the outcome. Self-administered surveys collected cross-sectional data between September 2017 and December 2021 from relatives participating in the CASCADE cohort. We used multivariable logistic regression with LASSO variable selection. Among n = 115 relatives who completed the baseline survey, 38% (n = 44) were in the GT (−) group. Being male (OR: 2.79, 95% CI: 1.10–7.10) and without a previous cancer diagnosis (OR: 4.47, 95% CI: 1.03–19.42) increased the odds of being untested by almost three times. Individuals from families with fewer tested relatives had 29% higher odds of being untested (OR: 0.71, 95% CI: 0.55–0.92). Reasons for forgoing cascade testing were: lack of provider recommendation, lack of time and interest in testing, being afraid of discrimination, and high out-of-pocket costs. Multilevel interventions designed to increase awareness about clinical implications of HBOC and LS in males, referrals from non-specialists, and support for testing multiple family members could improve the uptake of cascade testing. Full article

(This article belongs to the Special Issue Genetic Counseling and Genetic Testing in Precision Medicine)

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14 pages, 3045 KiB

Open AccessEditor’s ChoiceArticle

A Ready-to-Use Grading Tool for Facial Palsy Examiners—Automated Grading System in Facial Palsy Patients Made Easy

by Leonard Knoedler, Maximilian Miragall, Martin Kauke-Navarro, Doha Obed, Maximilian Bauer, Patrick Tißler, Lukas Prantl, Hans-Guenther Machens, Peter Niclas Broer, Helena Baecher, Adriana C. Panayi, Samuel Knoedler and Andreas Kehrer

J. Pers. Med. 2022, 12(10), 1739; https://doi.org/10.3390/jpm12101739 - 19 Oct 2022

Cited by 11 | Viewed by 2025

Abstract

Background: The grading process in facial palsy (FP) patients is crucial for time- and cost-effective therapy decision-making. The House-Brackmann scale (HBS) represents the most commonly used classification system in FP diagnostics. This study investigated the benefits of linking machine learning (ML) techniques with [...] Read more.

Background: The grading process in facial palsy (FP) patients is crucial for time- and cost-effective therapy decision-making. The House-Brackmann scale (HBS) represents the most commonly used classification system in FP diagnostics. This study investigated the benefits of linking machine learning (ML) techniques with the HBS. Methods: Image datasets of 51 patients seen at the Department of Plastic, Hand, and Reconstructive Surgery at the University Hospital Regensburg, Germany, between June 2020 and May 2021, were used to build the neural network. A total of nine facial poses per patient were used to automatically determine the HBS. Results: The algorithm had an accuracy of 98%. The algorithm processed the real patient image series (i.e., nine images per patient) in 112 ms. For optimized accuracy, we found 30 training runs to be the most effective training length. Conclusion: We have developed an easy-to-use, time- and cost-efficient algorithm that provides highly accurate automated grading of FP patient images. In combination with our application, the algorithm may facilitate the FP surgeon’s clinical workflow. Full article

(This article belongs to the Special Issue Computer Assisted Maxillo-Facial Surgery)

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9 pages, 1495 KiB

Open AccessArticle

Red Blood Cell Lifespan < 74 Days Can Clinically Reduce Hb1Ac Levels in Type 2 Diabetes

by Saijun Zhou, Rongna Dong, Junmei Wang, Li Zhang, Bai Yu, Xian Shao, Pufei Bai, Rui Zhang, Yongjian Ma and Pei Yu

J. Pers. Med. 2022, 12(10), 1738; https://doi.org/10.3390/jpm12101738 - 19 Oct 2022

Cited by 3 | Viewed by 1729

Abstract

Variations in the red blood cell (RBC) lifespan can affect glycosylated hemoglobin (HbA1c) test values, but there is still a lack of evidence regarding how and to what degree the RBC lifespan influences HbA1c in the type 2 diabetes mellitus (T2DM) population owing [...] Read more.

Variations in the red blood cell (RBC) lifespan can affect glycosylated hemoglobin (HbA1c) test values, but there is still a lack of evidence regarding how and to what degree the RBC lifespan influences HbA1c in the type 2 diabetes mellitus (T2DM) population owing to the restriction of traditional RBC lifespan detection means. In this study, we monitored 464 T2DM patients and 231 healthy control finger blood glucose levels at seven time points for three consecutive months. The HbA1c levels were assessed at the end of the third month as well as the RBC lifespan was measured through the CO breath test. T2DM patients were stratified into four quartile groups according to their RBC lifespans. There was no statistical significance in HbA1c among these four groups. However, the average blood glucose in the Q1 group was significantly higher than those in the other groups. Additionally, the contribution of RBC lifespan to HbA1c test value in the Q1 group was 14.07%, which was significantly higher than those in the other groups. Finally, we used multiple linear regression models to construct a mathematical formula to correct the HbA1c test value in the Q1 group, which would benefit the management of T2DM. Full article

(This article belongs to the Section Clinical Medicine, Cell, and Organism Physiology)

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8 pages, 803 KiB

Open AccessArticle

Serum Adiponectin, a Novel Biomarker Correlates with Skin Thickness in Systemic Sclerosis

by Giorgia Leodori, Chiara Pellicano, Valerio Basile, Amalia Colalillo, Luca Navarini, Antonietta Gigante, Francesca Gulli, Mariapaola Marino, Umberto Basile and Edoardo Rosato

J. Pers. Med. 2022, 12(10), 1737; https://doi.org/10.3390/jpm12101737 - 19 Oct 2022

Viewed by 1173

Abstract

The aim was to evaluate the longitudinal association between basal serum adiponectin and repeated measurements of skin thickness during 12 months of follow-up in systemic sclerosis (SSc) patients. We enrolled SSc patients with disease duration > 2 years in a prospective observational study. [...] Read more.

The aim was to evaluate the longitudinal association between basal serum adiponectin and repeated measurements of skin thickness during 12 months of follow-up in systemic sclerosis (SSc) patients. We enrolled SSc patients with disease duration > 2 years in a prospective observational study. Skin thickness was measured at baseline and after 12 months of follow-up with modified Rodnan skin score (mRSS). Baseline serum adiponectin was determined using a commercial ELISA kit. We enrolled 66 female SSc patients (median age 54 years, IQR 42–62 years). The median disease duration was 12 (IQR 8–16) years and median baseline serum adiponectin was 9.8 (IQR 5.6–15.6) mcg/mL. The median mRSS was 10 (IQR 6–18) at baseline and 12 (IQR 7–18) at follow-up. A significant correlation was observed between baseline serum adiponectin and disease duration (r = 0.264, p < 0.05), age (r = 0.515, p < 0.0001), baseline mRSS (r = −0.303, p < 0.05), and mRSS at follow-up (r = −0.322, p < 0.001). In multiple regression analysis, only mRSS at follow-up showed an inverse correlation with baseline serum adiponectin (β = −0.132, p < 0.01). The reduction in serum adiponectin levels is correlated with skin thickness. Full article

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26 pages, 3518 KiB

Open AccessReview

Nano-Clays for Cancer Therapy: State-of-the Art and Future Perspectives

by Francesca Persano and Stefano Leporatti

J. Pers. Med. 2022, 12(10), 1736; https://doi.org/10.3390/jpm12101736 - 19 Oct 2022

Cited by 4 | Viewed by 2459

Abstract

To date, cancer continues to be one of the deadliest diseases. Current therapies are often ineffective, leading to the urgency to develop new therapeutic strategies to improve treatments. Conventional chemotherapeutics are characterized by a reduced therapeutic efficacy, as well as them being responsible [...] Read more.

To date, cancer continues to be one of the deadliest diseases. Current therapies are often ineffective, leading to the urgency to develop new therapeutic strategies to improve treatments. Conventional chemotherapeutics are characterized by a reduced therapeutic efficacy, as well as them being responsible for important undesirable side effects linked to their non-specific toxicity. In this context, natural nanomaterials such as clayey mineral nanostructures of various shapes (flat, tubular, spherical and fibrous) with adjustable physico-chemical and morphological characteristics are emerging as systems with extraordinary potential for the delivery of different therapeutic agents to tumor sites. Thanks to their submicron size, high specific surface area, high adsorption capacity, chemical inertia and multilayer organization of 0.7 to 1 nm-thick sheets, they have aroused considerable interest among the scientific community as nano systems that are highly biocompatible in cancer therapy. In oncology, the nano-clays usually studied are halloysite, bentonite, laponite, kaolinite, montmorillonite and sepiolite. These are multilayered minerals that can act as nanocarriers (with a drug load generally between 1 and 10% by weight) for improved stabilization, efficient transport and the sustained and controlled release of a wide variety of anticancer agents. In particular, halloysite, montmorillonite and kaolinite are used to improve the dissolution of therapeutic agents and to delay and/or direct their release. In this review, we will examine and expose to the scientific community the extraordinary potential of nano-clays as unique crystalline systems in the treatment of cancer. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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8 pages, 2064 KiB

Open AccessCase Report

A New Mini-Invasive Approach for a Catastrophic Disease: Staged Endovascular and Endoscopic Treatment of Aorto-Esophageal Fistulas

by Federica Donato, Ivo Boskoski, Claudio Vincenzoni, Francesca Montanari, Giovanni Tinelli, Tommaso Donati and Yamume Tshomba

J. Pers. Med. 2022, 12(10), 1735; https://doi.org/10.3390/jpm12101735 - 19 Oct 2022

Cited by 5 | Viewed by 1178

Abstract

Aorto-esophageal fistula (AEF) is an uncommon but usually fatal disorder. Surgery with resection of an aneurysm and esophagus, in situ reconstruction of the descending aorta and omental flap installation offers the gold standard for the reduction of infections, but it is burdened by [...] Read more.

Aorto-esophageal fistula (AEF) is an uncommon but usually fatal disorder. Surgery with resection of an aneurysm and esophagus, in situ reconstruction of the descending aorta and omental flap installation offers the gold standard for the reduction of infections, but it is burdened by high intraoperative and perioperative mortality rates. We report our experience with a combined minimally invasive approach for the multi-stage treatment of three cases of aorto-esophageal fistula caused by thoracic aneurysm rupture. In all of the patients, the aneurysm was treated with thoracic endovascular aortic repair and the esophageal lesion was treated with esophageal endoprosthesis placement. According to our experience, the combined strategy of thoracic endovascular aortic repair (TEVAR) and esophageal less invasive endoscopic treatments represents an alternative solution in frail patients with high surgical risk. Full article

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9 pages, 1513 KiB

Open AccessArticle

Proposal for a Structured Outpatient Clinic for Dupilumab Treatment in Chronic Rhinosinusitis with Nasal Polyps in the First Year of Treatment

by Sara Torretta, Eugenio De Corso, Nicolò Nava, Francesca Fraccaroli, Silvia Mariel Ferrucci, Stefano Settimi, Claudio Montuori, Davide Paolo Porru, Camilla Spanu, Giuseppe D’Agostino, Angelo Valerio Marzano and Lorenzo Pignataro

J. Pers. Med. 2022, 12(10), 1734; https://doi.org/10.3390/jpm12101734 - 19 Oct 2022

Cited by 5 | Viewed by 2196

Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common disease of the nose and paranasal sinuses with important economic and sanitary burdens, as well as having a great impact on patients’ quality of life. In this field, a new therapeutic approach for those [...] Read more.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common disease of the nose and paranasal sinuses with important economic and sanitary burdens, as well as having a great impact on patients’ quality of life. In this field, a new therapeutic approach for those patients who have been described as affected by severe uncontrolled CRSwNP, resistant to medical and best surgical treatment, is represented by subcutaneous human monoclonal antibodies (including dupilumab) that block specific targets involved in the type 2 inflammatory pathway which most commonly drives CRSwNP pathophysiology. This paper aims to report our experience in the management of severe uncontrolled CRSwNP and, in particular, describe our diagnostic workup including baseline evaluation and follow-up visits in the first year of treatment. We also describe into detail our multidisciplinary approach to the disease. We finally report the outcomes of treatment in a real-life setting. In this outpatient real-life setting, our results confirmed the effectiveness of dupilumab in reducing the volume of nasal polyps and restoring nasal obstruction and sense of smell, as well as improving patients’ quality of life. The adherence to the dupilumab treatment was very high. The dose of administration was never modified in patients in the first year of treatment. All the patients respected the plan of the visits at proposed time points. We believe that the structural organization of our outpatient clinic appears to be functional: it allows us to study patients thoroughly before starting treatment and to make a proper follow-up after it starts. We believe that sharing both our strict clinical flowchart and growing experience with dupilumab with the medical community can lead to more standardized and effective pathways of care for CRSwNP patients. Full article

(This article belongs to the Section Clinical Medicine, Cell, and Organism Physiology)

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11 pages, 3853 KiB

Open AccessReview

Clinical Application of Ultra-High-Frequency Ultrasound

by Anna Russo, Alfonso Reginelli, Giorgia Viola Lacasella, Enrico Grassi, Michele Ahmed Antonio Karaboue, Tiziana Quarto, Gian Maria Busetto, Alberto Aliprandi, Roberta Grassi and Daniela Berritto

J. Pers. Med. 2022, 12(10), 1733; https://doi.org/10.3390/jpm12101733 - 19 Oct 2022

Cited by 17 | Viewed by 2559

Abstract

Musculoskeletal ultrasound involves the study of many superficial targets, especially in the hands, wrists, and feet. Many of these areas are within the first 3 cm of the skin surface and are ideal targets for ultra-high-frequency ultrasound. The high spatial resolution and the [...] Read more.

Musculoskeletal ultrasound involves the study of many superficial targets, especially in the hands, wrists, and feet. Many of these areas are within the first 3 cm of the skin surface and are ideal targets for ultra-high-frequency ultrasound. The high spatial resolution and the superb image quality achievable allow foreseeing a wider use of this novel technique, which has the potential to bring innovation to diagnostic imaging. Full article

(This article belongs to the Special Issue Personalized and Precision Medicine 2022)

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12 pages, 320 KiB

Open AccessArticle

Influence of Maternal and Paternal History of Mental Health in Clinical, Social Cognition and Metacognitive Variables in People with First-Episode Psychosis

by Sara Mendoza-García, Helena García-Mieres, Raquel Lopez-Carrilero, Julia Sevilla-Llewellyn-Jones, Irene Birulés, Ana Barajas, Ester Lorente-Rovira, Alfonso Gutiérrez-Zotes, Eva Grasa, Esther Pousa, Trini Pelaéz, Maria Luisa Barrigón, Fermin González-Higueras, Isabel Ruiz-Delgado, Jordi Cid, Roger Montserrat, Laia Martin-Iñigo, Berta Moreno-Kustner, Regina Vila-Bbadía, Luciana Díaz-Cutraro, Marina Verdaguer-Rodríguez, Marta Ferrer-Quintero, Paola Punsoda-Puche, Paula Barrau-Sastre, Steffen Moritz and Susana Ochoa Show full author list Hide full author list

J. Pers. Med. 2022, 12(10), 1732; https://doi.org/10.3390/jpm12101732 - 18 Oct 2022

Cited by 3 | Viewed by 1774

Abstract

This study investigates, for the first time, clinical, cognitive, social cognitive and metacognitive differences in people diagnosed with first-episode of psychosis (FEP) with and without a family history of mental disorder split by maternal and paternal antecedents. A total of 186 individuals with [...] Read more.

This study investigates, for the first time, clinical, cognitive, social cognitive and metacognitive differences in people diagnosed with first-episode of psychosis (FEP) with and without a family history of mental disorder split by maternal and paternal antecedents. A total of 186 individuals with FEP between 18 and 45 years old were recruited in community mental-health services. A transversal, descriptive, observational design was chosen for this study. Results suggest that there is a higher prevalence of maternal history of psychosis rather than paternal, and furthermore, these individuals exhibit a specific clinical, social and metacognitive profile. Individuals with a maternal history of mental disorder scored higher in delusional experiences, inhibition of the response to a stimulus and higher emotional irresponsibility while presenting a poorer overall functioning as compared to individuals without maternal history. Individuals with paternal history of mental disorder score higher in externalizing attributional bias, irrational beliefs of need for external validation and high expectations. This study elucidates different profiles of persons with FEP and the influence of the maternal and paternal family history on clinical, cognitive, social and metacognitive variables, which should be taken into account when offering individualized early treatment. Full article

16 pages, 1948 KiB

Open AccessArticle

Identification of Potential Repurposable Drugs in Alzheimer’s Disease Exploiting a Bioinformatics Analysis

by Giulia Fiscon, Pasquale Sibilio, Alessio Funari, Federica Conte and Paola Paci

J. Pers. Med. 2022, 12(10), 1731; https://doi.org/10.3390/jpm12101731 - 18 Oct 2022

Cited by 4 | Viewed by 2069

Abstract

Alzheimer’s disease (AD) is a neurologic disorder causing brain atrophy and the death of brain cells. It is a progressive condition marked by cognitive and behavioral impairment that significantly interferes with daily activities. AD symptoms develop gradually over many years and eventually become [...] Read more.

Alzheimer’s disease (AD) is a neurologic disorder causing brain atrophy and the death of brain cells. It is a progressive condition marked by cognitive and behavioral impairment that significantly interferes with daily activities. AD symptoms develop gradually over many years and eventually become more severe, and no cure has been found yet to arrest this process. The present study is directed towards suggesting putative novel solutions and paradigms for fighting AD pathogenesis by exploiting new insights from network medicine and drug repurposing strategies. To identify new drug–AD associations, we exploited SAveRUNNER, a recently developed network-based algorithm for drug repurposing, which quantifies the vicinity of disease-associated genes to drug targets in the human interactome. We complemented the analysis with an in silico validation of the candidate compounds through a gene set enrichment analysis, aiming to determine if the modulation of the gene expression induced by the predicted drugs could be counteracted by the modulation elicited by the disease. We identified some interesting compounds belonging to the beta-blocker family, originally approved for treating hypertension, such as betaxolol, bisoprolol, and metoprolol, whose connection with a lower risk to develop Alzheimer’s disease has already been observed. Moreover, our algorithm predicted multi-kinase inhibitors such as regorafenib, whose beneficial effects were recently investigated for neuroinflammation and AD pathology, and mTOR inhibitors such as sirolimus, whose modulation has been associated with AD. Full article

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13 pages, 440 KiB

Open AccessArticle

Analysis of Psychosomatic Disorders According to Age and Sex in a Rural Area: A Population-Based Study

by Elisabet Torrubia-Pérez, Silvia Reverté-Villarroya, José Fernández-Sáez and Maria-Antonia Martorell-Poveda

J. Pers. Med. 2022, 12(10), 1730; https://doi.org/10.3390/jpm12101730 - 18 Oct 2022

Cited by 1 | Viewed by 2934

Abstract

Psychosomatic disorders can develop unevenly depending on certain health determinants; therefore, the aim of this study was to analyze the prevalence of psychosomatic disorders and the differences by age and sex in a rural area. We conducted an observational descriptive retrospective population study [...] Read more.

Psychosomatic disorders can develop unevenly depending on certain health determinants; therefore, the aim of this study was to analyze the prevalence of psychosomatic disorders and the differences by age and sex in a rural area. We conducted an observational descriptive retrospective population study to determine the prevalence of 201 diagnoses of psychosomatic nature grouped into 25 diagnostic categories by sex and age groups. A total of 33,680 participants with a diagnosis of psychosomatic disorder were identified (64.6% women, 35.4% men). We found statistically significant differences based on sex in 13 of the 25 diagnostic categories previously defined. When we analyzed these categories by age, we found that women showed a higher probability, between 1.23 and 10.85 times, of suffering from most of these health issues. We also observed that the older the age group, the most often they had a diagnosis. Notably, more women seem to suffer from psychosomatic disorders when compared to men in the same situation. In most of these disorders, being of the female sex was a risk factor, and the older the participants, the greater the probability of developing a disorder. Full article

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8 pages, 828 KiB

Open AccessArticle

IL-2 and IL-1β Patient Immune Responses Are Critical Factors in SARS-CoV-2 Infection Outcomes

by Shereen Fawzy, Mesaik M. Ahmed, Badr A. Alsayed, Rashid Mir and Dnyanesh Amle

J. Pers. Med. 2022, 12(10), 1729; https://doi.org/10.3390/jpm12101729 - 17 Oct 2022

Cited by 3 | Viewed by 1425

Abstract

Background: Immune dysregulation has been linked to morbidity and mortality in COVID-19 patients. Understanding the immunology of COVID-19 is critical for developing effective therapies, diagnostics, and prophylactic strategies to control the disease. Aim: The aim of this study was to correlate cytokine and [...] Read more.

Background: Immune dysregulation has been linked to morbidity and mortality in COVID-19 patients. Understanding the immunology of COVID-19 is critical for developing effective therapies, diagnostics, and prophylactic strategies to control the disease. Aim: The aim of this study was to correlate cytokine and chemokine serum levels with COVID-19 disease severity and mortality. Subjects and Methods: A total of 60 hospitalized patients from the Tabuk region of Saudi Arabia with confirmed COVID-19 were included in the study. At hospital admission, the IL-1 β, IL-2, IL-8, IL-10, LT-B4, and CCL-2 serum levels were measured. The cytokine levels in COVID-19 patients were compared to the levels in 30 healthy matched control subjects. Results: The IL-1 β, IL-2, LTB-4, CCL-2, and IL-8 levels (but not IL-10) were significantly higher in all COVID-19 patients (47 survivors and 13 non-survivors) compared with the levels in the healthy control group. In the non-survivor COVID-19 patients, patients’ age, D-dimer, and creatinine kinase were significantly higher, and IL-1 β, IL-2, and IL-8 were significantly lower compared with the levels in the survivors. Conclusion: Mortality rates in COVID-19 patients are associated with increased age and a failure to mount an effective immune response rather than developing a cytokine storm. These results warrant the personalized treatment of COVID-19 patients based on cytokine profiling. Full article

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12 pages, 992 KiB

Open AccessArticle

Is the CYP2D6 Genotype Associated with Antipsychotic-Induced Weight Gain?

by Gesche Jürgens, Benjamin Skov Kaas-Hansen, Merete Nordentoft, Thomas Werge and Stig Ejdrup Andersen

J. Pers. Med. 2022, 12(10), 1728; https://doi.org/10.3390/jpm12101728 - 17 Oct 2022

Viewed by 1198

Abstract

Antipsychotic-induced weight gain (AIWG) is a serious adverse effect. Studies have linked genetically-predicted CYP2D6 metabolic capacity to AIWG. The evidence, however, is ambiguous. We performed multiple regression analyses examining the association between genetic-predicted CYP2D6 metabolic capacity and AIWG. Analyses were based on previously [...] Read more.

Antipsychotic-induced weight gain (AIWG) is a serious adverse effect. Studies have linked genetically-predicted CYP2D6 metabolic capacity to AIWG. The evidence, however, is ambiguous. We performed multiple regression analyses examining the association between genetic-predicted CYP2D6 metabolic capacity and AIWG. Analyses were based on previously unpublished data from an RCT investigating the clinical utility of routine genotyping of CYP2D6 and CYP2C19 in patients with schizophrenia. A total of 211 patients, corresponding to 71% of the original study population, were included. Our analyses indicated an effect of genetically predicted CYP2D6 metabolic capacity on AIWG with significant weight gain in both CYP2D6 poor metabolizers (PMs) (4.00 kg (95% CI: 0.80; 7.21)) and ultrarapid metabolizers (UMs) (6.50 kg (95% CI: 1.03; 12.0)). This finding remained stable after adjustment for covariates (PMs: 4.26 kg (0.88; 7.64), UMs: 7.26 kg (1.24; 13.3)). In addition to the CYP2D6 metabolic capacity, both baseline body mass index (−0.24 (95% CI: −0.44; −0.03)) and chlorpromazine equivalents per day (0.0041 (95% CI: 0.0005; 0.0077)) were statistically significantly associated with weight change in the adjusted analysis. Our results support that the genetically predicted CYP2D6 metabolic capacity matters for AIWG. Full article

(This article belongs to the Section Pharmacogenetics)

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34 pages, 7954 KiB

Open AccessArticle

Metabolomic Signatures of Autism Spectrum Disorder

by Danielle Brister, Shannon Rose, Leanna Delhey, Marie Tippett, Yan Jin, Haiwei Gu and Richard E. Frye

J. Pers. Med. 2022, 12(10), 1727; https://doi.org/10.3390/jpm12101727 - 17 Oct 2022

Cited by 9 | Viewed by 3839

Abstract

Autism Spectrum Disorder (ASD) is associated with many variations in metabolism, but the ex-act correlates of these metabolic disturbances with behavior and development and their links to other core metabolic disruptions are understudied. In this study, large-scale targeted LC-MS/MS metabolomic analysis was conducted [...] Read more.

Autism Spectrum Disorder (ASD) is associated with many variations in metabolism, but the ex-act correlates of these metabolic disturbances with behavior and development and their links to other core metabolic disruptions are understudied. In this study, large-scale targeted LC-MS/MS metabolomic analysis was conducted on fasting morning plasma samples from 57 children with ASD (29 with neurodevelopmental regression, NDR) and 37 healthy controls of similar age and gender. Linear model determined the metabolic signatures of ASD with and without NDR, measures of behavior and neurodevelopment, as well as markers of oxidative stress, inflammation, redox, methylation, and mitochondrial metabolism. MetaboAnalyst ver 5.0 (the Wishart Research Group at the University of Alberta, Edmonton, Canada) identified the pathways associated with altered metabolic signatures. Differences in histidine and glutathione metabolism as well as aromatic amino acid (AAA) biosynthesis differentiated ASD from controls. NDR was associated with disruption in nicotinamide and energy metabolism. Sleep and neurodevelopment were associated with energy metabolism while neurodevelopment was also associated with purine metabolism and aminoacyl-tRNA biosynthesis. While behavior was as-sociated with some of the same pathways as neurodevelopment, it was also associated with alternations in neurotransmitter metabolism. Alterations in methylation was associated with aminoacyl-tRNA biosynthesis and branched chain amino acid (BCAA) and nicotinamide metabolism. Alterations in glutathione metabolism was associated with changes in glycine, serine and threonine, BCAA and AAA metabolism. Markers of oxidative stress and inflammation were as-sociated with energy metabolism and aminoacyl-tRNA biosynthesis. Alterations in mitochondrial metabolism was associated with alterations in energy metabolism and L-glutamine. Using behavioral and biochemical markers, this study finds convergent disturbances in specific metabolic pathways with ASD, particularly changes in energy, nicotinamide, neurotransmitters, and BCAA, as well as aminoacyl-tRNA biosynthesis. Full article

(This article belongs to the Special Issue A Personalized Medicine Approach to the Diagnosis and Management of Autism Spectrum Disorder: Beyond Genetic Syndromes)

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12 pages, 1122 KiB

Open AccessArticle

Determinants of Treatment Benefit and Post-Treatment Survival for Patients with Hepatocellular Carcinoma Enrolled in Second-Line Trials after the Failure of Sorafenib Treatment

by Nicola Personeni, Tiziana Pressiani, Valentina Zanuso, Andrea Casadei-Gardini, Antonio D’Alessio, Martina Valgiusti, Vincenzo Dadduzio, Francesca Bergamo, Caterina Soldà, Mario Domenico Rizzato, Laura Giordano, Armando Santoro and Lorenza Rimassa

J. Pers. Med. 2022, 12(10), 1726; https://doi.org/10.3390/jpm12101726 - 17 Oct 2022

Viewed by 1441

Abstract

Second-line treatments are standard care for advanced hepatocellular carcinoma (HCC) patients with preserved liver function who are intolerant of or progress on first-line therapy. However, determinants of treatment benefit and post-treatment survival (PTS) remain unknown. HCC patients previously treated with sorafenib and enrolled [...] Read more.

Second-line treatments are standard care for advanced hepatocellular carcinoma (HCC) patients with preserved liver function who are intolerant of or progress on first-line therapy. However, determinants of treatment benefit and post-treatment survival (PTS) remain unknown. HCC patients previously treated with sorafenib and enrolled in second-line clinical trials were pooled according to the investigational treatment received and the subsequent regulatory approval: approved targeted agents and immune checkpoint inhibitors (AT) or other agents (OT) not subsequently approved. Univariate and multivariate analyses using Cox proportional hazards models established relationships among treatments received, clinical variables, and overall survival (OS) or PTS. For 174 patients (80 AT; 94 OT) analyzed, baseline factors for longer OS in multivariate analysis were second-line AT, absence of both portal vein thrombosis and extrahepatic spread (EHS). Treatment with AT (versus OT) was associated with significantly longer OS among patients with EHS (p_interaction = 0.005) and patients with low neutrophil-to-lymphocyte ratio (NLR; p_interaction = 0.032). Median PTS was 4.0 months (95% CI 2.8–5.3). At second-line treatment discontinuation, alpha-fetoprotein (AFP) levels <400 ng/dl, albumin-bilirubin (ALBI) grade 1, and enrolment onto subsequent trials independently predicted longer PTS. Treatment with AT, PVT, and EHS were prognostic factors for OS, while AFP, ALBI grade and enrolment onto a third-line trial were prognostic for PTS. Presence of EHS and low NLR were predictors of greater OS benefit from AT. Full article

(This article belongs to the Special Issue The Present and Future of Personalized Medicine in Oncology)

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10 pages, 1277 KiB

Open AccessBrief Report

Comparison of 0.12% Chlorhexidine and a New Bone Bioactive Liquid, BBL, in Mouthwash for Oral Wound Healing: A Randomized, Double Blind Clinical Human Trial

by Eduard Ferrés-Amat, Ashraf Al Madhoun, Elvira Ferrés-Amat, Neus Carrió, Miguel Barajas, Areej Said Al-Madhoun, Eduard Ferrés-Padró, Carles Marti and Maher Atari

J. Pers. Med. 2022, 12(10), 1725; https://doi.org/10.3390/jpm12101725 - 16 Oct 2022

Cited by 1 | Viewed by 2225

Abstract

Following surgery, healing within the oral cavity occurs in a hostile environment, and proper oral care and hygiene are required to accelerate recovery. The aim of the current study is to investigate and compare the bioreactivity characteristics of mouthwashes based on either chlorhexidine [...] Read more.

Following surgery, healing within the oral cavity occurs in a hostile environment, and proper oral care and hygiene are required to accelerate recovery. The aim of the current study is to investigate and compare the bioreactivity characteristics of mouthwashes based on either chlorhexidine (CHX) or a novel bone bioactive liquid (BBL) in terms of oral healing within seven days application post-surgery. A randomized, double blind clinical trial was conducted in 81 patients, wherein the mouthwashes were applied twice a day for a period of 7 days. The visual analog scale (VAS) protocol was applied to determine pain index scores. Early wound healing index (EHI) score was determined for evaluating oral cavity healing progress. No adverse effects were observed using the mouthwashes, but CHX application resulted in stained teeth. Applications of both CHX and BBL were sufficient to reduce pain over a period of 7 days. However, the BBL group demonstrated a statistically significant reduction in VAS scores starting on day 4. The EHI scores were significantly higher in the BBL group compared with the CHX group, independent of tooth location. No differences in either VAS or EHI scores due to gender were observed. Compared with the commercially available CHX mouthwash, application of the BBL mouthwash reduced pain and accelerated oral cavity healing to a greater extent, suggesting it effectively improves the oral cavity microenvironment at the wound site in mediating soft tissue regeneration. Full article

(This article belongs to the Special Issue Prevention and Management of Oral Healthcare)

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12 pages, 2672 KiB

Open AccessArticle

The Trochlear Groove of a Femoral Component Designed for Kinematic Alignment Is Lateral to the Quadriceps Line of Force and Better Laterally Covers the Anterior Femoral Resection Than a Mechanical Alignment Design

by Elliot Sappey-Marinier, Stephen M. Howell, Alexander J. Nedopil and Maury L. Hull

J. Pers. Med. 2022, 12(10), 1724; https://doi.org/10.3390/jpm12101724 - 16 Oct 2022

Cited by 5 | Viewed by 1859

Abstract

Background: A concern about kinematically aligned (KA) total knee arthroplasty (TKA) is that it relies on femoral components designed for mechanical alignment (MAd-FC) that could affect patellar tracking, in part, because of a trochlear groove orientation that is typically 6° from [...] Read more.

Background: A concern about kinematically aligned (KA) total knee arthroplasty (TKA) is that it relies on femoral components designed for mechanical alignment (MAd-FC) that could affect patellar tracking, in part, because of a trochlear groove orientation that is typically 6° from vertical. KA sets the femoral component coincident to the patient’s pre-arthritic distal and posterior femoral joint lines and restores the Q-angle, which varies widely. Relative to KA and the native knee, aligning the femoral component with MA changes most distal joint lines and Q-angles, and rotates the posterior joint line externally laterally covering the anterior femoral resection. Whether switching from a MAd- to a KAd-FC with a wider trochlear groove orientation of 20.5° from vertical results in radiographic measures known to promote patellar tracking is unknown. The primary aim was to determine whether a KAd-FC sets the trochlear groove lateral to the quadriceps line of force (QLF), better laterally covers the anterior femoral resection, and reduces lateral patella tilt relative to a MAd-FC. The secondary objective was to determine at six weeks whether the KAd-FC resulted in a higher complication rate, less knee extension and flexion, and lower clinical outcomes. Methods: Between April 2019 and July 2022, two surgeons performed sequential bilateral unrestricted caliper-verified KA TKA with manual instruments on thirty-six patients with a KAd- and MAd-FC in opposite knees. An observer measured the angle between a line best-fit to the deepest valley of the trochlea and a line representing the QLF that indicated the patient’s Q-angle. When the trochlear groove was lateral or medial relative to the QLF, the angle is denoted + or −, and the femoral component included or excluded the patient’s Q-angle, respectively. Software measured the lateral undercoverage of the anterior femoral resection on a Computed Tomography (CT) scan, and the patella tilt angle (PTA) on a skyline radiograph. Complications, knee extension and flexion measurements, Oxford Knee Score, KOOS Jr, and Forgotten Joint Score were recorded pre- and post-operatively (at 6 weeks). A paired Student’s T-test determined the difference between the KA TKAs with a KAd-FC and MAd-FC with a significance set at p < 0.05. Results: The final analysis included thirty-five patients. The 20.5° trochlear groove of the KAd-FC was lateral to the QLF in 100% (15 ± 3°) of TKAs, which was greater than the 69% (1 ± 3°) lateral to the QLF with the 6° trochlear groove of the MAd-FC (p < 0.001). The KAd-FC’s 2 ± 1.9 mm lateral undercoverage of the anterior femoral resection was less than the 4.4 ± 1.5 mm for the MAd-FC (p < 0.001). The PTA, complication rate, knee extension and flexion, and clinical outcome measures did not differ between component designs. Conclusions: The KA TKA with a KAd-FC resulted in a trochlear groove lateral to the QLF that included the Q-angle in all patients, and negligible lateral undercoverage of the anterior femoral resection. These newly described radiographic parameters could be helpful when investigating femoral components designed for KA with the intent of promoting patellofemoral kinematics. Full article

(This article belongs to the Section Methodology, Drug and Device Discovery)

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