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Which Therapy for Non-Type(T)2/T2-Low Asthma
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Diabetic and Hypertensive Retinopathy Screening in Fundus Images Using Artificially Intelligent Shallow Architectures
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Oncological Response and Predictive Biomarkers for the Checkpoint Inhibitors in Castration-Resistant Metastatic Prostate Cancer: A Systematic Review and Meta-Analysis
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Recommendations for the Diagnosis and Treatment of Multiple Sclerosis Relapses
Journal Description
Journal of Personalized Medicine
Journal of Personalized Medicine
is an international, peer-reviewed, open access journal on personalized medicine, published monthly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, and many other databases.
- Journal Rank: JCR - Q1 (Health Care Sciences & Services) / CiteScore - Q2 (Medicine, miscellaneous)
- Rapid Publication: manuscripts are peer-reviewed and a first decision provided to authors approximately 22.5 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the second half of 2021).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Impact Factor:
4.945 (2020)
;
5-Year Impact Factor:
4.994 (2020)
Latest Articles
Precision Medicine in Head and Neck Cancers: Genomic and Preclinical Approaches
J. Pers. Med. 2022, 12(6), 854; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12060854 (registering DOI) - 24 May 2022
Abstract
Head and neck cancers (HNCs) represent the sixth most widespread malignancy worldwide. Surgery, radiotherapy, chemotherapeutic and immunotherapeutic drugs represent the main clinical approaches for HNC patients. Moreover, HNCs are characterised by an elevated mutational load; however, specific genetic mutations or biomarkers have not
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Head and neck cancers (HNCs) represent the sixth most widespread malignancy worldwide. Surgery, radiotherapy, chemotherapeutic and immunotherapeutic drugs represent the main clinical approaches for HNC patients. Moreover, HNCs are characterised by an elevated mutational load; however, specific genetic mutations or biomarkers have not yet been found. In this scenario, personalised medicine is showing its efficacy. To study the reliability and the effects of personalised treatments, preclinical research can take advantage of next-generation sequencing and innovative technologies that have been developed to obtain genomic and multi-omic profiles to drive personalised treatments. The crosstalk between malignant and healthy components, as well as interactions with extracellular matrices, are important features which are responsible for treatment failure. Preclinical research has constantly implemented in vitro and in vivo models to mimic the natural tumour microenvironment. Among them, 3D systems have been developed to reproduce the tumour mass architecture, such as biomimetic scaffolds and organoids. In addition, in vivo models have been changed over the last decades to overcome problems such as animal management complexity and time-consuming experiments. In this review, we will explore the new approaches aimed to improve preclinical tools to study and apply precision medicine as a therapeutic option for patients affected by HNCs.
Full article
(This article belongs to the Special Issue Personalized Medicine in Cancer Therapy: Mechanism, Approaches and Techniques)
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Open AccessArticle
Laser Doppler Flowmetry Combined with Spectroscopy to Determine Peripheral Tissue Perfusion and Oxygen Saturation: A Pilot Study in Healthy Volunteers and Patients with Peripheral Arterial Disease
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, , , , , and
J. Pers. Med. 2022, 12(6), 853; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12060853 (registering DOI) - 24 May 2022
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Background: In this study, we assessed the ability of the EPOS system (Perimed AB, Järfälla, Stockholm, Sweden) to detect differences in tissue perfusion between healthy volunteers and patients with peripheral arterial disease (PAD) with different severity of disease. Methods: This single-center prospective pilot
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Background: In this study, we assessed the ability of the EPOS system (Perimed AB, Järfälla, Stockholm, Sweden) to detect differences in tissue perfusion between healthy volunteers and patients with peripheral arterial disease (PAD) with different severity of disease. Methods: This single-center prospective pilot study included 10 healthy volunteers and 20 patients with PAD scheduled for endovascular therapy (EVT). EPOS measurements were performed at rest at 32 °C and 44 °C, followed by transcutaneous oxygen pressure (TcPo2) measurements. The measurements were performed on the dorsal and medial side of the foot, as well as the lateral side of the calf. EPOS parameters included hemoglobin oxygen saturation (HbSo2) and speed-resolved red blood cell (RBC) perfusion. Results: HbSo2 at 44 °C was significantly different between the three groups for all measurement locations. The overall speed-resolved RBC perfusion at 44 °C was statistically significant between the groups on the dorsal and medial side of the foot but not on the calf. TcPo2 values were not significantly different between the three groups. Conclusions: This study demonstrates that the EPOS system can depict differences in tissue perfusion between healthy volunteers, patients with Fontaine class IIb PAD, and those with Fontaine class III or IV PAD but only after heating to 44 °C.
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Open AccessArticle
Antibody Arrays Identified Cycle-Dependent Plasma Biomarker Candidates of Peritoneal Endometriosis
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, , , , , and
J. Pers. Med. 2022, 12(6), 852; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12060852 (registering DOI) - 24 May 2022
Abstract
Endometriosis is an estrogen-dependent inflammatory disease affecting women in their reproductive age. Due to non-specific symptoms, women with endometriosis are often misdiagnosed or are accurately diagnosed only after several years. Diagnosis of peritoneal endometriosis is especially challenging and relies only on laparoscopic surgery.
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Endometriosis is an estrogen-dependent inflammatory disease affecting women in their reproductive age. Due to non-specific symptoms, women with endometriosis are often misdiagnosed or are accurately diagnosed only after several years. Diagnosis of peritoneal endometriosis is especially challenging and relies only on laparoscopic surgery. To date, different molecules have been proposed as potential non-invasive biomarkers of endometriosis; however, none have been confirmed as clinically useful. Therefore, this study aimed to discover novel plasma biomarker candidates for peritoneal endometriosis using an antibody array platform. This study included patients with endometriosis-like symptoms characterized by the absence (controls) or presence of peritoneal endometriosis (cases) after laparoscopic surgery and histological evaluation. Patients were further divided into secretory and proliferative groups, according to the phase of their menstrual cycle. Their plasma samples were collected and analyzed on an antibody array platform targeting more than 1350 proteins with over 1820 antibodies. In the proliferative group, the analysis revealed three differential proteins between cases and controls: ITB3, ITA2B2, and ACVL-1. In the secretory group, none of the examined proteins reached the log-fold change (logFC) and significance thresholds simultaneously. The potential of the identified differential proteins as plasma biomarker candidates for peritoneal endometriosis should be evaluated on a larger cohort, and their role in endometriosis should be investigated in further studies.
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(This article belongs to the Special Issue Endometriosis: Advances in Diagnosis and Treatment)
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Open AccessArticle
Deep Learning-Based Grimace Scoring Is Comparable to Human Scoring in a Mouse Migraine Model
J. Pers. Med. 2022, 12(6), 851; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12060851 - 24 May 2022
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Pain assessment is essential for preclinical and clinical studies on pain. The mouse grimace scale (MGS), consisting of five grimace action units, is a reliable measurement of spontaneous pain in mice. However, MGS scoring is labor-intensive and time-consuming. Deep learning can be applied
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Pain assessment is essential for preclinical and clinical studies on pain. The mouse grimace scale (MGS), consisting of five grimace action units, is a reliable measurement of spontaneous pain in mice. However, MGS scoring is labor-intensive and time-consuming. Deep learning can be applied for the automatic assessment of spontaneous pain. We developed a deep learning model, the DeepMGS, that automatically crops mouse face images, predicts action unit scores and total scores on the MGS, and finally infers whether pain exists. We then compared the performance of DeepMGS with that of experienced and apprentice human scorers. The DeepMGS achieved an accuracy of 70–90% in identifying the five action units of the MGS, and its performance (correlation coefficient = 0.83) highly correlated with that of an experienced human scorer in total MGS scores. In classifying pain and no pain conditions, the DeepMGS is comparable to the experienced human scorer and superior to the apprentice human scorers. Heatmaps generated by gradient-weighted class activation mapping indicate that the DeepMGS accurately focuses on MGS-relevant areas in mouse face images. These findings support that the DeepMGS can be applied for quantifying spontaneous pain in mice, implying its potential application for predicting other painful conditions from facial images.
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Open AccessReview
Paucigranulocytic Asthma: Potential Pathogenetic Mechanisms, Clinical Features and Therapeutic Management
by
, , , and
J. Pers. Med. 2022, 12(5), 850; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12050850 (registering DOI) - 23 May 2022
Abstract
Asthma is a heterogeneous disease usually characterized by chronic airway inflammation, in which several phenotypes have been described, related to the age of onset, symptoms, inflammatory characteristics and treatment response. The identification of the inflammatory phenotype in asthma is very useful, since it
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Asthma is a heterogeneous disease usually characterized by chronic airway inflammation, in which several phenotypes have been described, related to the age of onset, symptoms, inflammatory characteristics and treatment response. The identification of the inflammatory phenotype in asthma is very useful, since it allows for both the recognition of the asthmatic triggering factor as well as the optimization of treatment The paucigranulocytic phenotype of asthma (PGA) is characterized by sputum eosinophil levels <1–3% and sputum neutrophil levels < 60%. The precise characteristics and the pathobiology of PGA are not fully understood, and, in some cases, it seems to represent a previous eosinophilic phenotype with a good response to anti-inflammatory treatment. However, many patients with PGA remain uncontrolled and experience asthmatic symptoms and exacerbations, irrespective of the low grade of airway inflammation. This observation leads to the hypothesis that PGA might also be either a special phenotype driven by different kinds of cells, such as macrophages or mast cells, or a non-inflammatory phenotype with a low grade of eosinophilic inflammation. In this review, we aim to describe the special characteristics of PGA and the potential therapeutic interventions that could be offered to these patients.
Full article
(This article belongs to the Special Issue Asthma: From Phenotypes to Personalized Medicine)
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Open AccessFeature PaperArticle
Gender-Specific Differences in the Intensive Care Treatment of COVID-19 Patients
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, , , , , , , , , , , , , , , and
J. Pers. Med. 2022, 12(5), 849; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12050849 (registering DOI) - 23 May 2022
Abstract
Background: Gender-specific differences in the outcome of COVID-19 patients requiring intensive care treatment have been reported. However, a potential association with ICU therapy remains elusive. Methods: A total of 224 consecutive patients (63 women) treated for severe COVID-19 disease requiring mechanical ventilation were
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Background: Gender-specific differences in the outcome of COVID-19 patients requiring intensive care treatment have been reported. However, a potential association with ICU therapy remains elusive. Methods: A total of 224 consecutive patients (63 women) treated for severe COVID-19 disease requiring mechanical ventilation were screened for the study. After propensity score matching for gender, 40 men and 40 women were included in the study. Comparative analysis was conducted for laboratory parameters, ICU therapy and complications (pulmonary embolism, thrombosis, stroke, and ventricular arrhythmias), and outcome (mortality). Results: Male patients had significantly higher levels of CRP (p = 0.012), interleukin-6 (p = 0.020) and creatinine (p = 0.027), while pH levels (p = 0.014) were significantly lower compared to females. Male patients had longer intubation times (p = 0.017), longer ICU stays (p = 0.022) and higher rates of catecholamine dependence (p = 0.037). Outcome, complications and ICU therapy did not differ significantly between both groups. Conclusion: The present study represents the first matched comparison of male and female COVID-19 patients requiring intensive care treatment. After propensity matching, male patients still displayed a higher disease severity. This was reflected in higher rates of vasopressors, duration of ICU stay and duration of intubation. In contrast, no significant differences were observed in mortality rates, organ replacement therapy and complications during ICU stay.
Full article
(This article belongs to the Special Issue Personalized Medicine Interdisciplinary Aspects and Sex Gender-Specific Differences)
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Open AccessArticle
Cardiovascular Risk Assessment by SCORE2 Predicts Risk for Colorectal Neoplasia and Tumor-Related Mortality
by
, , , , , , , , , and
J. Pers. Med. 2022, 12(5), 848; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12050848 - 23 May 2022
Abstract
Objectives: The European Society of Cardiology endorsed SCORE2 to assess cardiovascular risk. The aim of this observational, retrospective study was to assess whether SCORE2 is associated with colorectal neoplasia in an asymptomatic screening population. Further, we evaluated if SCORE2 predicts tumor-related mortality. Methods:
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Objectives: The European Society of Cardiology endorsed SCORE2 to assess cardiovascular risk. The aim of this observational, retrospective study was to assess whether SCORE2 is associated with colorectal neoplasia in an asymptomatic screening population. Further, we evaluated if SCORE2 predicts tumor-related mortality. Methods: We included 3408 asymptomatic patients who underwent a screening colonoscopy. We calculated SCORE2 for each participant and stratified patients according to their predicted 10-year risk of cardiovascular disease: SCORE2 0–4.9%, SCORE2 5–9.9%, and SCORE2 ≥ 10%. We assessed the association between SCORE2 as a continuous variable, the presence of colorectal neoplasia using multilevel logistic regression, and SCORE2 and mortality using Cox regression. Results: In total, 1537 patients had a SCORE2 of 0–4.9%, 1235 a SCORE2 of 5–9.9%, and 636 a SCORE2 ≥ 10%. The respective rates of colorectal neoplasia were 20%, 37%, and 44%. SCORE2 was associated with the presence of any (OR 1.11 95%CI 1.09–1.12; p < 0.001) and advanced colorectal neoplasia (OR 1.06 95%CI 1.08–1.13; p < 0.001) in univariate analysis. After multivariable adjustment (age, sex, family history, and metabolic syndrome) a higher SCORE2 remained associated with higher odds for any (aOR 1.04 95%CI 1.02–1.06; p = 0.001) and advanced (aOR 1.06 95%CI 1.03–1.10; p < 0.001) colorectal neoplasia. SCORE2 was associated with both all-cause (HR 1.11 95%CI 1.09–1.14; p < 0.001) and tumor-related mortality (HR 1.10 95%CI 1.05–1.14; p < 0.001). Conclusions: We found that SCORE2 is associated with the presence of colorectal neoplasia. Clinicians could kill two birds with one stone calculating SCORE2. In patients with a high SCORE2, screening colonoscopy aside from cardiovascular risk mitigation could improve outcomes.
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(This article belongs to the Section Epidemiology)
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Characterization of Retinal Drusen in Subjects at High Genetic Risk of Developing Sporadic Alzheimer’s Disease: An Exploratory Analysis
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J. Pers. Med. 2022, 12(5), 847; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12050847 - 23 May 2022
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Having a family history (FH+) of Alzheimer’s disease (AD) and being a carrier of at least one ɛ4 allele of the ApoE gene are two of the main risk factors for the development of AD. AD and age-related macular degeneration (AMD) share one
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Having a family history (FH+) of Alzheimer’s disease (AD) and being a carrier of at least one ɛ4 allele of the ApoE gene are two of the main risk factors for the development of AD. AD and age-related macular degeneration (AMD) share one of the main risk factors, such as age, and characteristics including the presence of deposits (Aβ plaques in AD and drusen in AMD); however, the role of apolipoprotein E isoforms in both pathologies is controversial. We analyzed and characterized retinal drusen by optical coherence tomography (OCT) in subjects, classifying them by their AD FH (FH- or FH+) and their allelic characterization of ApoE ɛ4 (ApoE ɛ4- or ApoE ɛ4+) and considering cardiovascular risk factors (hypercholesterolemia, hypertension, and diabetes mellitus). In addition, we analyzed the choroidal thickness by OCT and the area of the foveal avascular zone with OCTA. We did not find a relationship between a family history of AD or any of the ApoE isoforms and the presence or absence of drusen. Subjects with drusen show choroidal thinning compared to patients without drusen, and thinning could trigger changes in choroidal perfusion that may give rise to the deposits that generate drusen.
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Open AccessReview
Personalized Management of Patients with Chronic Rhinosinusitis with Nasal Polyps in Clinical Practice: A Multidisciplinary Consensus Statement
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, , , , , , , , , , , and
J. Pers. Med. 2022, 12(5), 846; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12050846 - 23 May 2022
Abstract
Chronic rhinosinusitis (CRS) is a sino-nasal chronic inflammatory disease, occurring in 5–15% of the general population. CRS with nasal polyps (CRSwNP) is present in up to 30% of the CRS population. One-third of CRSwNP patients suffer from disease that is uncontrolled by current
[...] Read more.
Chronic rhinosinusitis (CRS) is a sino-nasal chronic inflammatory disease, occurring in 5–15% of the general population. CRS with nasal polyps (CRSwNP) is present in up to 30% of the CRS population. One-third of CRSwNP patients suffer from disease that is uncontrolled by current standards of care. Biologics are an emerging treatment option for patients with severe uncontrolled CRSwNP, but their positioning in the treatment algorithm is under discussion. Effective endotyping of CRSwNP patients who could benefit from biologics treatment is required, as suggested by international guidelines. Other issues affecting management include comorbidities, such as allergy, non-steroidal anti-inflammatory drug–exacerbated respiratory disease, and asthma. Therefore, the choice of treatment in CRSwNP patients depends on many factors. A multidisciplinary approach may improve CRSwNP management in patients with comorbidities, but currently there is no shared management model. We summarize the outcomes of a Delphi process involving a multidisciplinary panel of otolaryngologists, pulmonologists, and allergist-immunologists involved in the management of CRSwNP, who attempted to reach consensus on key statements relating to the diagnosis, endotyping, classification and management (including the place of biologics) of CRSwNP patients.
Full article
(This article belongs to the Special Issue Personalized Medicine in Otorhinolaryngology)
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The Impact of Hypoglycemic Therapy on the Prognosis for Acute Coronary Syndrome in Patients with Type 2 Diabetes
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, , , , , , and
J. Pers. Med. 2022, 12(5), 845; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12050845 (registering DOI) - 22 May 2022
Abstract
The article discusses particular circumstances of acute coronary syndrome (ACS) in patients with type 2 diabetes (T2D). In addition, the available literature data and clinical guidelines reflecting the role of hypoglycemic therapy as a cardioprotection factor in ACS are analyzed. The article considers
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The article discusses particular circumstances of acute coronary syndrome (ACS) in patients with type 2 diabetes (T2D). In addition, the available literature data and clinical guidelines reflecting the role of hypoglycemic therapy as a cardioprotection factor in ACS are analyzed. The article considers possible protective molecular mechanisms of various groups of drugs in ischemic cardiomyocytes.
Full article
Open AccessProtocol
TMS Database Registry Consortium Research Project in Japan (TReC-J) for Future Personalized Psychiatry
J. Pers. Med. 2022, 12(5), 844; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12050844 - 22 May 2022
Abstract
The registry project led by the Japanese Society for Clinical Transcranial Magnetic Stimulation (TMS) Research aims to establish a centralized database of epidemiological, clinical, and biological data on TMS therapy for refractory psychiatric disorders, including treatment-resistant depression, as well as to contribute to
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The registry project led by the Japanese Society for Clinical Transcranial Magnetic Stimulation (TMS) Research aims to establish a centralized database of epidemiological, clinical, and biological data on TMS therapy for refractory psychiatric disorders, including treatment-resistant depression, as well as to contribute to the elucidation of the therapeutic mechanism of TMS therapy and to the validation of its efficacy by analyzing and evaluating these data in a systematic approach. The objective of this registry project is to collect a wide range of complex data linked to patients with various neuropsychiatric disorders who received TMS therapy throughout Japan, and to make effective use of these data to promote cross-sectional and longitudinal exploratory observational studies. Research utilizing this registry project will be conducted in a multicenter, non-invasive, retrospective, and prospective observational research study design, regardless of the framework of insurance medical care, private practice, or clinical research. Through the establishment of the registry, which aims to make use of data, we will advance the elucidation of treatment mechanisms and identification of predictors of therapeutic response to TMS therapy for refractory psychiatric disorders on a more real-world research basis. Furthermore, as a future vision, we aim to develop novel neuromodulation medical devices, algorithms for predicting treatment efficacy, and digital therapeutics based on the knowledge generated from this TMS registry database.
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(This article belongs to the Special Issue The Current State of Psychiatry: Personalized Medicine and Treatment)
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Open AccessArticle
In Vivo Accuracy of a New Digital Planning System in Terms of Jaw Relation, Extent of Surgical Movements and the Hierarchy of Stability in Orthognathic Surgery
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, , , , and
J. Pers. Med. 2022, 12(5), 843; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12050843 - 21 May 2022
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This retrospective cohort study compares the virtual planned and postoperative jaw positions in patients undergoing orthognathic surgery. Surgery was virtually planned with the Digital Münster Model Surgery system (DMMS). Primary outcome: Spatial difference in the maxillo-mandibulo relation between virtual planning and postoperative result.
[...] Read more.
This retrospective cohort study compares the virtual planned and postoperative jaw positions in patients undergoing orthognathic surgery. Surgery was virtually planned with the Digital Münster Model Surgery system (DMMS). Primary outcome: Spatial difference in the maxillo-mandibulo relation between virtual planning and postoperative result. Secondary outcome: Possible relationship between the measured differences and surgical movements as well as the postoperative stability according to Proffit. Ninety female and sixty-one male patients were included in the study. The average translation errors were 0.54 ± 0.50 mm (anteroposterior), 0.37 ± 0.33 mm (mediolateral), and 0.33 ± 0.28 mm (superoinferior). Orientation errors were 0.86 ± 0.79 degrees (yaw), 0.54 ± 0.48 degrees (roll), and 0.90 ± 0.72 degrees (pitch). The surgical procedures do not differ with respect to their error sizes. Maxilla forward and class II maxilla up with mandible forward are the most precise procedures. Most significant differences were found in the anteroposterior direction, whereby the extent of the surgical movement has no effect on the magnitude of the error. The process of planning with the DMMS followed by surgery is highly accurate and shows error values well below the clinically accepted limit of two millimeters in translation and four degrees in rotation.
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Open AccessArticle
CD44 Mediates Oral Squamous Cell Carcinoma-Promoting Activity of MRE11 via AKT Signaling
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, , , , , , , and
J. Pers. Med. 2022, 12(5), 841; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12050841 - 21 May 2022
Abstract
Oral cancer is one of the highest-incidence malignancies worldwide, with the occurrence of oral squamous cell carcinoma (OSCC) being the most frequently diagnosed form. A barrier for oral cancer management may arise from tumor cells that possess properties of cancer stemness, which has
[...] Read more.
Oral cancer is one of the highest-incidence malignancies worldwide, with the occurrence of oral squamous cell carcinoma (OSCC) being the most frequently diagnosed form. A barrier for oral cancer management may arise from tumor cells that possess properties of cancer stemness, which has been recognized as a crucial factor in tumor recurrence and metastasis. As such, understanding the molecular mechanisms underlying these tumor cells may provide insights for improving cancer treatment. MRE11 is the core protein of the RAD50/MRE11/NBS1 complex with a primary role in DNA damage repair, and it has been diversely associated with tumor development including OSCC. In this study, we aimed to investigate the engagement of CD44, a cancer stemness marker functioning in the control of cell growth and motility, in OSCC malignancy under the influence of MRE11. We found that overexpression of MRE11 enhanced CD44 expression and tumorsphere formation in OSCC cells, whereas knockdown of MRE11 reduced these phenomena. In addition, the MRE11-promoted tumorsphere formation or cell migration ability was compromised in OSCC cells carrying siRNA that targets CD44, as was the MRE11-promoted AKT phosphorylation. These were further supported by analyzing clinical samples, where higher CD44 expression was associated with lymph node metastasis. Additionally, a positive correlation between the expression of MRE11 and CD44, or that of CD44 and phosphorylated AKT, was observed in OSCC tumor tissues. Finally, the expression of CD44 was found to be higher in the metastatic lung nodules from mice receiving tail vein-injection with MRE11-overexpressing OSCC cells compared with control mice, and a positive correlation between CD44 and phosphorylated AKT was also observed in these metastatic lung nodules. Altogether, our current study revealed a previously unidentified mechanism linking CD44 and AKT in MRE11-promoted OSCC malignancy, which may shed light to the development of novel therapeutic strategies in consideration of this new pathway in OSCC.
Full article
(This article belongs to the Special Issue Personalized Medicine in Oral Cancer)
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Open AccessSystematic Review
The Impact of Concomitant Proton Pump Inhibitors on Immunotherapy Efficacy among Patients with Urothelial Carcinoma: A Meta-Analysis
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, , , , , , , and
J. Pers. Med. 2022, 12(5), 842; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12050842 - 20 May 2022
Abstract
Background. Immune checkpoint inhibitors (ICIs) have recently represented a breakthrough in urothelial carcinoma (UC). Proton pump inhibitors (PPIs) are routinely used for extended time periods in UC patients, with these agents having potentially and frequently undervalued effects on ICIs efficacy. Methods. We performed
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Background. Immune checkpoint inhibitors (ICIs) have recently represented a breakthrough in urothelial carcinoma (UC). Proton pump inhibitors (PPIs) are routinely used for extended time periods in UC patients, with these agents having potentially and frequently undervalued effects on ICIs efficacy. Methods. We performed a meta-analysis aimed at investigating the impact of concomitant PPI administration on progression-free survival (PFS) and overall survival (OS) among patients receiving immunotherapy for metastatic UC. Results. Two studies encompassing a total of 1015 patients were included. The pooled Hazard Ratios (HRs) for OS and PFS were 1.55 (95% CI, 1.31–1.84) and 1.43 (95% CI, 1.23–1.66), respectively, suggesting that the administration of PPIs was negatively associated with PFS and with OS in UC patients treated with ICIs. Conclusions. The current meta-analysis represents the first study to provide a systematic evaluation of the impact of concomitant PPI use in UC patients treated with ICIs. Further studies are warranted on this topic to clarify the relationship between gut microbiome, antiacid exposure, and cancer immunotherapy. In the current era of medical oncology, progress in this setting will require the collaboration of basic science and clinical research to optimize systemic treatment and to improve the outcomes of UC patients receiving ICIs.
Full article
(This article belongs to the Special Issue Precision Medicine and Molecular Diagnosis for Urogenital Cancer)
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Open AccessReview
Diffuse Intrinsic Pontine Glioma: Molecular Landscape, Evolving Treatment Strategies and Emerging Clinical Trials
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, , , and
J. Pers. Med. 2022, 12(5), 840; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12050840 (registering DOI) - 20 May 2022
Abstract
Diffuse intrinsic pontine glioma (DIPG) is a type of intrinsic brainstem glial tumor that occurs primarily in the pediatric population. DIPG is initially diagnosed based on clinical symptoms and the characteristic location on imaging. Histologically, these tumors are characterized by a heterogenous population
[...] Read more.
Diffuse intrinsic pontine glioma (DIPG) is a type of intrinsic brainstem glial tumor that occurs primarily in the pediatric population. DIPG is initially diagnosed based on clinical symptoms and the characteristic location on imaging. Histologically, these tumors are characterized by a heterogenous population of cells with multiple genetic mutations and high infiltrative capacity. The most common mutation seen in this group is a lysine to methionine point mutation seen at position 27 (K27M) within histone 3 (H3). Tumors with the H3 K27M mutation, are considered grade 4 and are now categorized within the H3 K27-altered diffuse midline glioma category by World Health Organization classification. Due to its critical location and aggressive nature, DIPG is resistant to the most eradicative treatment and is universally fatal; however, modern advances in the surgical techniques resulting in safe biopsy of the lesion have significantly improved our understanding of this disease at the molecular level. Genomic analysis has shown several mutations that play a role in the pathophysiology of the disease and can be targeted therapeutically. In this review, we will elaborate on DIPG from general aspects and the evolving molecular landscape. We will also review innovative therapeutic options that have been trialed along with new promising treatments on the horizon.
Full article
(This article belongs to the Special Issue Personalized Medicine in Brain Tumors)
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Open AccessArticle
Associations between Choriocapillaris Flow on Optical Coherence Tomography Angiography and Cardiovascular Risk Profiles of Patients with Acute Myocardial Infarction
J. Pers. Med. 2022, 12(5), 839; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12050839 - 20 May 2022
Abstract
We evaluated the association between macular perfusion assessed via optical coherence tomography angiography (OCTA) and the cardiovascular risk profiles of patients with acute myocardial infarction (AMI). Patients with AMI who underwent comprehensive ophthalmological examinations and retinal OCTA were evaluated retrospectively. Retinal OCTA was
[...] Read more.
We evaluated the association between macular perfusion assessed via optical coherence tomography angiography (OCTA) and the cardiovascular risk profiles of patients with acute myocardial infarction (AMI). Patients with AMI who underwent comprehensive ophthalmological examinations and retinal OCTA were evaluated retrospectively. Retinal OCTA was performed for each patient within 3 days of admission. Quantitative analyses of the vessel density (VD) of the superficial capillary plexus (SCP) layers, deep capillary plexus layers (DCP), and choriocapillaris were performed after image processing. The 10-year risk of atherosclerotic cardiovascular disease (ASCVD), Global Registry of Acute Coronary Events (GRACE) score, reduction of atherothrombosis for continued health (REACH) score, and thrombolysis in myocardial infarction (TIMI) risk score were assessed. Sixty patients were included. VD in SCP and DCP was not associated with a 10-year ASCVD risk; however, choriocapillaris flow void features were significantly correlated with the 10-year ASCVD risk: decreased count, increased average size, and increased signal void area were correlated with increased 10-year ASCVD risk, GRACE score, REACH score, and TIMI risk score. In the multivariate analysis, a 10-year ASCVD risk (adjusted odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01–1.08) and brain natriuretic peptide (adjusted OR, 1.00; 95% CI, 1.00–1.01) were significantly associated with the highest tertile of the average size of the choriocapillaris. Choriocapillaris flow void features measured using OCTA were associated with cardiovascular risk profiles in patients with AMI. OCTA may be used as an indicator of cardiovascular risk profiles and could improve cardiovascular risk assessments.
Full article
(This article belongs to the Topic Retinal Imaging and Systemic Vascular Disease: Recent Advances and Perspective)
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Open AccessArticle
Constipation Symptoms in Multiple System Atrophy Using Rome Criteria and Their Impact on Personalized Medicine
J. Pers. Med. 2022, 12(5), 838; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12050838 - 20 May 2022
Abstract
Constipation is one of the most common non-motor symptoms in multiple system atrophy (MSA); however, it has not been evaluated according to the standard diagnostic criteria for constipation in patients with MSA. We evaluated the characteristics of constipation in patients with MSA by
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Constipation is one of the most common non-motor symptoms in multiple system atrophy (MSA); however, it has not been evaluated according to the standard diagnostic criteria for constipation in patients with MSA. We evaluated the characteristics of constipation in patients with MSA by using Rome criteria (Rome III), which has been validated and the widely used for gastrointestinal disorders. Fifty-one patients with MSA (29 female) were enrolled in the study. Based on the Rome III criteria, constipation was diagnosed in 29 patients (56.9%); irritable bowel syndrome was not detected. Thirty-seven patients (72.5%) were aware of their constipation. The most common constipation symptom was the sensation of anorectal obstruction (68.6%). Patients’ self-awareness of constipation was most strongly correlated to the sensation of incomplete evacuation (odds ratio: 7.377, 95% confidence interval: 1.402–38.817). The number of constipation-related symptoms was correlated with the total levodopa equivalent dose (p < 0.05). Rome criteria, which can detect various constipation symptoms, are useful for evaluating constipation in MSA, and these findings may greatly impact personalized medicine.
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(This article belongs to the Special Issue Neuromuscular and Neurodegenerative Diseases: Towards Personalized Medicine, Therapeutics and Improved Mechanistic Understanding)
Open AccessArticle
Studies in Rats of Combined Muscle and Liver Perfusion and of Muscle Extract Indicate That Contractions Release a Muscle Hormone Directly Enhancing Hepatic Glycogenolysis
J. Pers. Med. 2022, 12(5), 837; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12050837 - 20 May 2022
Abstract
Background: Established neuroendocrine signals do not sufficiently account for the exercise-induced increase in glucose production. Using an innovative, yet classical cross-circulation procedure, we studied whether contracting muscle produces a factor that directly stimulates hepatic glycogenolysis. Methods: Isolated rat hindquarters were perfused in series
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Background: Established neuroendocrine signals do not sufficiently account for the exercise-induced increase in glucose production. Using an innovative, yet classical cross-circulation procedure, we studied whether contracting muscle produces a factor that directly stimulates hepatic glycogenolysis. Methods: Isolated rat hindquarters were perfused in series with isolated livers. Results: Stimulation of the sciatic nerve of one or both legs resulted in an increase in force, which rapidly waned. During one-legged contractions, hepatic glucose production increased initially (from −0.9 ± 0.5 (mean ± SE) to 3.3 ± 0.7 µmol/min, p < 0.05). The peak did not differ significantly from that seen after 20 nM of epinephrine (5.1 ± 1.2 µmol/min, p > 0.05). In response to two-legged contractions, the increase in hepatic glucose production (to 5.4 ± 1.3 µmol/min) was higher (p < 0.05) and lasted longer than that seen during one-legged contractions. During contractions, peak hepatic glucose output exceeded concomitant hepatic lactate uptake (p < 0.05), and glucose output decreased to basal levels, while lactate uptake rose to a plateau. Furthermore, in separate experiments an increase in lactate supply to isolated perfused livers increased lactate uptake, but not glucose output. In intact rats, intra-arterial injection of extract made from mixed leg muscle elicited a prolonged increase (p < 0.05) in plasma glucose concentration (from 5.2 ± 0.1 mM to 8.3 ± 1.5 mM). In perfused livers, muscle extract increased glucose output dose dependently. Fractionation by chromatography of the extract showed that the active substance had a MW below 2000. Conclusion: This study provides evidence that contracting skeletal muscle may produce a hormone with a MW below 2000, which enhances hepatic glycogenolysis according to energy needs. Further chemical characterization is warranted.
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(This article belongs to the Section Mechanisms of Diseases)
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Open AccessSystematic Review
BMI at Discharge from Treatment Predicts Relapse in Anorexia Nervosa: A Systematic Scoping Review
by
, , , , , , and
J. Pers. Med. 2022, 12(5), 836; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12050836 - 20 May 2022
Abstract
Background: Anorexia nervosa (AN) has high rates of enduring disease and mortality. Currently, there is insufficient knowledge on the predictors of relapse after weight normalization and this is why a systematic literature review was performed. Methods: PubMed, EMBASE, PsychInfo, and Cochrane databases were
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Background: Anorexia nervosa (AN) has high rates of enduring disease and mortality. Currently, there is insufficient knowledge on the predictors of relapse after weight normalization and this is why a systematic literature review was performed. Methods: PubMed, EMBASE, PsychInfo, and Cochrane databases were searched for literature published until 13 July 2021. All study designs were eligible for inclusion if they focused on predictors of relapse after weight normalization in AN. Individual study definitions of relapse were used, and in general, this was either a drop in BMI and/or reccurrence of AN symptoms. Results: The database search identified 11,507 publications, leaving 9511 publications after the removal of duplicates and after a review of abstracts and titles; 191 were selected for full-text review. Nineteen publications met the criteria and included 1398 AN patients and 39 healthy controls (HC) from adults and adolescents (ages range 11–73 years). The majority used a prospective observational study design (12 studies), a few used a retrospective observational design (6 studies), and only one was a non-randomized control trial (NRCT). Sample sizes ranged from 16 to 191 participants. BMI or measures of body fat and leptin levels at discharge were the strongest predictors of relapse with an approximate relapse rate of 50% at 12 months. Other predictors included signs of eating disorder psychopathology at discharge. Conclusions: BMI at the end of treatment is a predictor of relapse in AN, which is why treatment should target a BMI well above 20. Together with the time to relapse, these outcomes are important to include in the evaluation of current and novel treatments in AN and for benchmarking.
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(This article belongs to the Special Issue Biomarkers and Clinical Research in Eating Disorders)
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Open AccessArticle
Association of a Common NOS1AP Variant with Attenuation of QTc Prolongation in Men with Heroin Dependence Undergoing Methadone Treatment
by
, , , , , , , , and
J. Pers. Med. 2022, 12(5), 835; https://0-doi-org.brum.beds.ac.uk/10.3390/jpm12050835 - 20 May 2022
Abstract
Background: The effects of methadone-induced severe prolongation of the corrected QT interval (QTc) and sudden cardiac death appear unpredictable and sex-dependent. Genetic polymorphisms in the nitric oxide synthase 1 adaptor protein (NOS1AP) have been implicated in QTc prolongation in general populations.
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Background: The effects of methadone-induced severe prolongation of the corrected QT interval (QTc) and sudden cardiac death appear unpredictable and sex-dependent. Genetic polymorphisms in the nitric oxide synthase 1 adaptor protein (NOS1AP) have been implicated in QTc prolongation in general populations. We investigated whether common NOS1AP variants interact with methadone in relation to QTc prolongation in patients with heroin dependence. Methods: We genotyped 17 NOS1AP variants spanning the entire gene in heroin-dependent patients who received a 12-lead electrocardiography (ECG) examination both at baseline and during maintenance methadone treatment in Cohort 1 and only during maintenance methadone treatment in Cohort 2. The QT interval was measured automatically by the Marquette 12SL program, and was corrected for heart rate using Bazett’s formula. Results: Cohort 1 consisted of 122 patients (age: 37.65 ± 8.05 years, 84% male, methadone dosage: 42.54 ± 22.17 mg/day), and Cohort 2 comprised of 319 patients (age: 36.9 ± 7.86 years, 82% male, methadone dosage: 26.08 ± 15.84 mg/day), with complete genotyping data for analyses. Before methadone, the QTc intervals increased with increasing age (r = 0.3541, p < 0.001); the age-adjusted QTc showed dose-dependent prolongation in men (r = 0.6320, p < 0.001), but abbreviation in women (r = −0.5348, p = 0.018) in Cohort 1. The pooled genotype-specific analysis of the two cohorts revealed that the QTc interval was significantly shorter in male carriers of the rs164148 AA variant than in male carriers of the reference GG genotype (GG: n = 262, QTc = 423 ± 1.4 ms; AA: n = 10, QTc = 404.1 ± 7 ms, p = 0.009), according to univariate analysis. The QTc remained shorter in male carriers of the rs164148 AA variant compared to GG genotype (423 ± 1.4 ms vs. 405.9 ± 6.9 ms, p = 0.016) in multivariate analysis after adjusting for age and methadone dosage. A cut-off QTc interval of <410 ms identifies 100% of AA carriers compared to none of GG carriers when receiving a daily methadone dosage of 30.6 ± 19.3 mg. There was no significant gene-drug interaction in contributing to the adjusted QTc (p = 0.2164) in male carriers of the rs164148 variants. Conclusions: Carriers of a common NOS1AP rs164148 AA genotype variant were associated with a shorter QTc interval in men receiving maintenance methadone treatment. This genetic polymorphism attenuates the QTc-prolonging effect by methadone, and thus may explain at least in part the unpredictable and heterogeneous risks for severe QTc prolongation and sudden cardiac death in patients on methadone.
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(This article belongs to the Special Issue The Challenges and Prospects in Cardiology)
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