Journal of Personalized Medicine

15 pages, 893 KB

Open AccessEditor’s ChoiceReview

Enhancing Radiotherapy Workflow for Head and Neck Cancer with Artificial Intelligence: A Systematic Review

by Ciro Franzese, Damiano Dei, Nicola Lambri, Maria Ausilia Teriaca, Marco Badalamenti, Leonardo Crespi, Stefano Tomatis, Daniele Loiacono, Pietro Mancosu and Marta Scorsetti

J. Pers. Med. 2023, 13(6), 946; https://doi.org/10.3390/jpm13060946 - 2 Jun 2023

Cited by 14 | Viewed by 3683

Abstract

Background: Head and neck cancer (HNC) is characterized by complex-shaped tumors and numerous organs at risk (OARs), inducing challenging radiotherapy (RT) planning, optimization, and delivery. In this review, we provided a thorough description of the applications of artificial intelligence (AI) tools in the [...] Read more.

Background: Head and neck cancer (HNC) is characterized by complex-shaped tumors and numerous organs at risk (OARs), inducing challenging radiotherapy (RT) planning, optimization, and delivery. In this review, we provided a thorough description of the applications of artificial intelligence (AI) tools in the HNC RT process. Methods: The PubMed database was queried, and a total of 168 articles (2016–2022) were screened by a group of experts in radiation oncology. The group selected 62 articles, which were subdivided into three categories, representing the whole RT workflow: (i) target and OAR contouring, (ii) planning, and (iii) delivery. Results: The majority of the selected studies focused on the OARs segmentation process. Overall, the performance of AI models was evaluated using standard metrics, while limited research was found on how the introduction of AI could impact clinical outcomes. Additionally, papers usually lacked information about the confidence level associated with the predictions made by the AI models. Conclusions: AI represents a promising tool to automate the RT workflow for the complex field of HNC treatment. To ensure that the development of AI technologies in RT is effectively aligned with clinical needs, we suggest conducting future studies within interdisciplinary groups, including clinicians and computer scientists. Full article

(This article belongs to the Special Issue Artificial Intelligence (AI) in Radiation Oncology)

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19 pages, 674 KB

Open AccessEditor’s ChoiceReview

Current Surgical Techniques in the Treatment of Adult Developmental Dysplasia of the Hip

by Anand S. Dhaliwal, Muzammil Akhtar, Daniel I. Razick, Arya Afzali, Ethan Wilson and Alexander J. Nedopil

J. Pers. Med. 2023, 13(6), 942; https://doi.org/10.3390/jpm13060942 - 1 Jun 2023

Cited by 6 | Viewed by 5420

Abstract

The surgical protocols currently used for the treatment of developmental dysplasia of the hip (DDH) are varied, with sufficient differences in clinical outcomes that warrant a review of the role of practicing orthopedic surgeons. This paper aims to summarize the current novel techniques [...] Read more.

The surgical protocols currently used for the treatment of developmental dysplasia of the hip (DDH) are varied, with sufficient differences in clinical outcomes that warrant a review of the role of practicing orthopedic surgeons. This paper aims to summarize the current novel techniques within the realm of surgical treatment for adult DDH, thus serving as a guide to surgeons looking to quickly familiarize themselves with available techniques. We performed computer systematic literature searches of the Embase and PubMed databases from 2010 to 2 April 2022. Study parameters as well as their respective patient reported outcomes (PROMs) were described in detail and compiled into diagrams. Two novel techniques were identified for the treatment of borderline or low-grade DDH. Six techniques which included modifications to the Bernese periacetabular osteotomy (PAO) were identified for the treatment of symptomatic DDH. Three techniques which include combinations of arthroscopy and osteotomy were identified for the treatment of DDH with concomitant hip pathologies such as cam deformities. Finally, six techniques, all of which are modifications to total hip arthroplasty (THA), were identified for the treatment of high-grade DDH. The techniques detailed in this review therefore equip surgeons with the necessary knowledge to improve outcomes in patients with varying degrees of DDH. Full article

(This article belongs to the Special Issue Cutting-Edge in Arthroplasty: Before, While and after Surgery)

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13 pages, 1044 KB

Open AccessEditor’s ChoiceArticle

Restless Legs Syndrome in Parkinson’s Disease

by Ştefania Diaconu, Laura Irincu, Larisa Ungureanu, Bogdan Ciopleiaș, Diana Țînț and Cristian Falup-Pecurariu

J. Pers. Med. 2023, 13(6), 915; https://doi.org/10.3390/jpm13060915 - 30 May 2023

Cited by 14 | Viewed by 3439

Abstract

Background: Restless legs syndrome (RLS) might worsen sleep quality and quality of life in people with Parkinson’s disease (PwPD). Objective: The main aim of the present study is to explore the associations between RLS and sleep, quality of life and other non-motor symptoms [...] Read more.

Background: Restless legs syndrome (RLS) might worsen sleep quality and quality of life in people with Parkinson’s disease (PwPD). Objective: The main aim of the present study is to explore the associations between RLS and sleep, quality of life and other non-motor symptoms (NMS) in a sample of PwPD. Methods: We compared the clinical features of 131 PwPD with and without RLS, in a cross-sectional study. We used several validated scales for assessment: the International Restless Legs Syndrome Study Group rating scale (IRLS), Parkinson’s Disease Sleep Scale version 2 (PDSS-2), Parkinson’s Disease Questionnaire (PDQ-39), Non-Motor Symptoms Questionnaire (NMSQ) and International Parkinson and Movement Disorder Society Non-Motor Rating Scale (MDS-NMS). Results: Thirty-five patients (26.71%) out of the total PwPD met the RLS diagnostic criteria, without significant differences between male (57.14%) and female (42.87%) (p = 0.431). Higher total scores of PDSS-2 were recorded among PwPD + RLS (p < 0.001), suggesting worse sleep quality. Significant correlations were observed between the diagnosis of RLS and some types of pain (especially nocturnal pain), physical fatigue and probable sleep-disordered breathing, according to the MDS-NMSS assessment. Conclusions: RLS has a high frequency in PwPD and it requires proper management, considering its consequences on sleep and quality of life. Full article

(This article belongs to the Section Epidemiology)

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13 pages, 1316 KB

Open AccessEditor’s ChoiceReview

Ophthalmic Manifestations in Fabry Disease: Updated Review

by Gloria Gambini, Luca Scartozzi, Federico Giannuzzi, Matteo Mario Carlà, Francesco Boselli, Tomaso Caporossi, Umberto De Vico, Antonio Baldascino and Stanislao Rizzo

J. Pers. Med. 2023, 13(6), 904; https://doi.org/10.3390/jpm13060904 - 27 May 2023

Cited by 14 | Viewed by 5185

Abstract

Fabry disease (FD) is an X-linked lysosomal storage disorder, causing Gb-3 (globotriaosylceramide) buildup in cellular lysosomes throughout the body, in particular in blood vessel walls, neuronal cells, and smooth muscle. The gradual accumulation of this glycosphingolipid in numerous eye tissues causes conjunctival vascular [...] Read more.

Fabry disease (FD) is an X-linked lysosomal storage disorder, causing Gb-3 (globotriaosylceramide) buildup in cellular lysosomes throughout the body, in particular in blood vessel walls, neuronal cells, and smooth muscle. The gradual accumulation of this glycosphingolipid in numerous eye tissues causes conjunctival vascular abnormalities, corneal epithelial opacities (cornea verticillata), lens opacities, and retinal vascular abnormalities. Although a severe vision impairment is rare, these abnormalities are diagnostic indicators and prognostics for severity. Cornea verticillata is the most common ophthalmic feature in both hemizygous men and heterozygous females. Vessel tortuosity has been linked to a faster disease progression and may be useful in predicting systemic involvement. New technologies such as optical coherence tomography angiography (OCTA) are useful for monitoring retinal microvasculature alterations in FD patients. Along with OCTA, corneal topographic analysis, confocal microscopy, and electro-functional examinations, contributed to the recognition of ocular abnormalities and have been correlated with systemic involvement. We offer an update regarding FD ocular manifestations, focusing on findings derived from the most recent imaging modalities, to optimize the management of this pathology. Full article

(This article belongs to the Special Issue Update and Perspectives on Corneal Diseases)

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15 pages, 1026 KB

Open AccessEditor’s ChoiceReview

Genetic Evaluation and Screening in Cardiomyopathies: Opportunities and Challenges for Personalized Medicine

by Sahana Aiyer, Emilia Kalutskaya, Arianne C. Agdamag and W. H. Wilson Tang

J. Pers. Med. 2023, 13(6), 887; https://doi.org/10.3390/jpm13060887 - 24 May 2023

Cited by 13 | Viewed by 3075

Abstract

Cardiomyopathy is a major cause of heart failure caused by abnormalities of the heart muscles that make it harder for it to fill or eject blood. With technological advances, it is important for patients and families to understand that there are potential monogenic [...] Read more.

Cardiomyopathy is a major cause of heart failure caused by abnormalities of the heart muscles that make it harder for it to fill or eject blood. With technological advances, it is important for patients and families to understand that there are potential monogenic etiologies of cardiomyopathy. A multidisciplinary approach to clinical genetic screening for cardiomyopathies involving genetic counseling and clinical genetic testing is beneficial for patients and families. With early identification of inherited cardiomyopathy, patients can initiate guideline-directed medical therapies earlier, resulting in a greater likelihood of improving prognoses and health outcomes. Identifying impactful genetic variants will also allow for cascade testing to determine at-risk family members through clinical (phenotype) screening and risk stratification. Addressing genetic variants of uncertain significance and causative variants that may change in pathogenicity is also important to consider. This review will dive into the clinical genetic testing approaches for the various cardiomyopathies, the significance of early detection and treatment, the value of family screening, the personalized treatment process associated with genetic evaluation, and current strategies for clinical genetic testing outreach. Full article

(This article belongs to the Topic Advances in Genetics and Precision Medicine in Human Diseases)

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12 pages, 886 KB

Open AccessEditor’s ChoiceArticle

Local Treatment of Triple-Negative Breast Cancer: Is Mastectomy Superior to Breast-Conserving Surgery?

by Alba Di Leone, Antonio Franco, Francesca Zotta, Lorenzo Scardina, Margherita Sicignano, Enrico Di Guglielmo, Virginia Castagnetta, Stefano Magno, Daniela Terribile, Alejandro Martin Sanchez, Gianluca Franceschini and Riccardo Masetti

J. Pers. Med. 2023, 13(5), 865; https://doi.org/10.3390/jpm13050865 - 21 May 2023

Cited by 7 | Viewed by 3113

Abstract

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer that lacks the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). TNBC accounts for about 15% of breast cancers and has a poorer prognosis [...] Read more.

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer that lacks the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). TNBC accounts for about 15% of breast cancers and has a poorer prognosis as compared with other subtypes of breast cancer. The more rapid onset of this cancer and its aggressiveness have often convinced breast surgeons that mastectomy could provide better oncological results. However, there is no relevant clinical trial that has assessed differences between breast-conserving surgery (BCS) and mastectomy (M) in these patients. This population-based study aimed to investigate the distinct outcomes between conservative treatment and M in a case series of 289 patients with TNBC treated over a 9-year period. This monocentric study retrospectively evaluated patients with TNBC who underwent upfront surgery at Fondazione Policlinico Agostino Gemelli IRCCS, in Rome, between 1 January 2013 and 31 December 2021. First, the patients were divided in two groups according to the surgical treatment received: BCS vs. M. Then, the patients were stratified into four risk subclasses based on combined T and N pathological staging (T1N0, T1N+, T2-4N0 and T2-4N+). The primary endpoint of the study was to evaluate locoregional disease-free survival (LR-DFS), distant disease-free survival (DDFS) and overall survival (OS) in the different subclasses. We analyzed 289 patients that underwent either breast-conserving surgery (247/289, 85.5%) or mastectomy (42/289, 14.5%). After a median follow-up of 43.2 months (49.7, 22.2–74.3), 28 patients (9.6%) developed a locoregional recurrence, 27 patients (9.0%) showed systemic recurrence and 19 patients (6.5%) died. No significant differences due to type of surgical treatment were observed in the different risk subclasses in terms of locoregional disease-free survival, distant disease-free survival and overall survival. With the limits of a retrospective, single-center study, our data seem to indicate similar efficacy in terms of locoregional control, distant metastasis and overall survival with the use of upfront breast-conserving surgery as compared with radical surgery in the treatment of TNBC. Therefore, TNBC should not be considered to be a contraindication for breast conservation. Full article

(This article belongs to the Section Personalized Therapy in Clinical Medicine)

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13 pages, 1747 KB

Open AccessEditor’s ChoiceReview

Predicting Hospital Ward Admission from the Emergency Department: A Systematic Review

by Nekane Larburu, Laiene Azkue and Jon Kerexeta

J. Pers. Med. 2023, 13(5), 849; https://doi.org/10.3390/jpm13050849 - 18 May 2023

Cited by 12 | Viewed by 4331

Abstract

Background: The emergency department (ED) is often overburdened, due to the high influx of patients and limited availability of attending physicians. This situation highlights the need for improvement in the management of, and assistance provided in the ED. A key point for this [...] Read more.

Background: The emergency department (ED) is often overburdened, due to the high influx of patients and limited availability of attending physicians. This situation highlights the need for improvement in the management of, and assistance provided in the ED. A key point for this purpose is the identification of patients with the highest risk, which can be achieved using machine learning predictive models. The objective of this study is to conduct a systematic review of predictive models used to detect ward admissions from the ED. The main targets of this review are the best predictive algorithms, their predictive capacity, the studies’ quality, and the predictor variables. Methods: This review is based on PRISMA methodology. The information has been searched in PubMed, Scopus and Google Scholar databases. Quality assessment has been performed using the QUIPS tool. Results: Through the advanced search, a total of 367 articles were found, of which 14 were of interest that met the inclusion criteria. Logistic regression is the most used predictive model, achieving AUC values between 0.75–0.92. The two most used variables are the age and ED triage category. Conclusions: artificial intelligence models can contribute to improving the quality of care in the ED and reducing the burden on healthcare systems. Full article

(This article belongs to the Collection Advances of Emergency and Intensive Care)

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19 pages, 359 KB

Open AccessEditor’s ChoiceReview

Cortisol and the Dexamethasone Suppression Test as a Biomarker for Melancholic Depression: A Narrative Review

by Martin M. Schumacher and Jacopo Santambrogio

J. Pers. Med. 2023, 13(5), 837; https://doi.org/10.3390/jpm13050837 - 16 May 2023

Cited by 15 | Viewed by 7951

Abstract

The dexamethasone suppression test (DST) assesses the functionality of the HPA axis and can be regarded as the first potential biomarker in psychiatry. In 1981, a group of researchers at the University of Michigan published a groundbreaking paper regarding its use for diagnosing [...] Read more.

The dexamethasone suppression test (DST) assesses the functionality of the HPA axis and can be regarded as the first potential biomarker in psychiatry. In 1981, a group of researchers at the University of Michigan published a groundbreaking paper regarding its use for diagnosing melancholic depression, reporting a diagnostic sensitivity of 67% and a specificity of 95%. While this study generated much enthusiasm and high expectations in the field of biological psychiatry, subsequent studies produced equivocal results, leading to the test being rejected by the American Psychiatric Association. The scientific reasons leading to the rise and fall of the DST are assessed in this review, suggestions are provided as to how the original test can be improved, and its potential applications in clinical psychiatry are discussed. An improved, standardized, and validated version of the DST would be a biologically meaningful and useful biomarker in psychiatry, providing a tool for clinicians caring for depressed patients in the areas of diagnosis, treatment, and prognosis, and predicting the risk of suicide. Additionally, such a test could be a crucial part in the generation of biologically homogenous patient cohorts, necessary for the successful development of new psychotropic medications. Full article

(This article belongs to the Special Issue Biomarkers in Psychiatric Disorders)

13 pages, 1112 KB

Open AccessEditor’s ChoiceArticle

Association of Sex Differences with Mortality and Organ Dysfunction in Patients with Sepsis and Septic Shock

by Caspar Mewes, Julius Runzheimer, Carolin Böhnke, Benedikt Büttner, José Hinz, Michael Quintel and Ashham Mansur

J. Pers. Med. 2023, 13(5), 836; https://doi.org/10.3390/jpm13050836 - 15 May 2023

Cited by 8 | Viewed by 2694

Abstract

Background: Despite recent advances in the clinical management and understanding of sepsis and septic shock, these complex clinical syndromes continue to have high mortality rates. The effect of sex on these diseases’ mortality, clinical presentation and morbidity remains controversial. This study aimed to [...] Read more.

Background: Despite recent advances in the clinical management and understanding of sepsis and septic shock, these complex clinical syndromes continue to have high mortality rates. The effect of sex on these diseases’ mortality, clinical presentation and morbidity remains controversial. This study aimed to investigate the association of sex with mortality and organ dysfunction in patients with sepsis and septic shock. Methods: Prospectively enrolled patients with clinically defined sepsis and septic shock in three intensive care units at University Medical Center Göttingen, Germany, were investigated. The primary outcomes were 28- and 90-day mortality, while the secondary endpoints included the evaluation of organ dysfunction as measured by clinical scores and laboratory parameters. Results: A total of 737 septic patients were enrolled, including 373 in septic shock, 484 males, and 253 females. No significant differences in 28- and 90-day mortality were observed in the cohort. However, men with sepsis had significantly higher SOFA scores, SOFA respiratory and renal subscores, bilirubin and creatinine values, and lower weight-adapted urine outputs, indicating higher organ dysfunction compared to women. Conclusions: Our findings revealed notable differences in organ dysfunction between male and female patients, with males exhibiting more pronounced dysfunction across multiple clinical indicators. These results highlight the potential influence of sex on sepsis disease severity and suggest the need for tailored approaches in sepsis management according to patient sex. Full article

(This article belongs to the Special Issue Sepsis Management and Critical Care)

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12 pages, 299 KB

Open AccessFeature PaperEditor’s ChoiceReview

Precision Medicine in Fatty Liver Disease/Non-Alcoholic Fatty Liver Disease

by Laura Valenzuela-Vallejo, Despina Sanoudou and Christos S. Mantzoros

J. Pers. Med. 2023, 13(5), 830; https://doi.org/10.3390/jpm13050830 - 14 May 2023

Cited by 23 | Viewed by 5002

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, and is related to fatal and non-fatal liver, metabolic, and cardiovascular complications. Its non-invasive diagnosis and effective treatment remain an unmet clinical need. NAFLD is a heterogeneous disease that is most [...] Read more.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, and is related to fatal and non-fatal liver, metabolic, and cardiovascular complications. Its non-invasive diagnosis and effective treatment remain an unmet clinical need. NAFLD is a heterogeneous disease that is most commonly present in the context of metabolic syndrome and obesity, but not uncommonly, may also be present without metabolic abnormalities and in subjects with normal body mass index. Therefore, a more specific pathophysiology-based subcategorization of fatty liver disease (FLD) is needed to better understand, diagnose, and treat patients with FLD. A precision medicine approach for FLD is expected to improve patient care, decrease long-term disease outcomes, and develop better-targeted, more effective treatments. We present herein a precision medicine approach for FLD based on our recently proposed subcategorization, which includes the metabolic-associated FLD (MAFLD) (i.e., obesity-associated FLD (OAFLD), sarcopenia-associated FLD (SAFLD, and lipodystrophy-associated FLD (LAFLD)), genetics-associated FLD (GAFLD), FLD of multiple/unknown causes (XAFLD), and combined causes of FLD (CAFLD) as well as advanced stage fibrotic FLD (FAFLD) and end-stage FLD (ESFLD) subcategories. These and other related advances, as a whole, are expected to enable not only improved patient care, quality of life, and long-term disease outcomes, but also a considerable reduction in healthcare system costs associated with FLD, along with more options for better-targeted, more effective treatments in the near future. Full article

(This article belongs to the Special Issue From Basic to Clinical Research: Toward Precision Medicine for Metabolic Diseases)

13 pages, 672 KB

Open AccessEditor’s ChoiceArticle

Efficacy and Safety of Axiostat^® Hemostatic Dressing in Aiding Manual Compression Closure of the Femoral Arterial Access Site in Patients Undergoing Endovascular Treatments: A Preliminary Clinical Experience in Two Centers

by Roberto Minici, Raffaele Serra, Claudio Maglia, Giuseppe Guzzardi, Marco Spinetta, Federico Fontana, Massimo Venturini and Domenico Laganà

J. Pers. Med. 2023, 13(5), 812; https://doi.org/10.3390/jpm13050812 - 11 May 2023

Cited by 13 | Viewed by 4128

Abstract

Background: Hemostasis of the femoral arterial access site by manual compression or a vascular closure device is critical to the safe completion of any endovascular procedure. Previous investigations evaluated the hemostatic efficacy at the radial access site of some chitosan-based hemostatic pads. This [...] Read more.

Background: Hemostasis of the femoral arterial access site by manual compression or a vascular closure device is critical to the safe completion of any endovascular procedure. Previous investigations evaluated the hemostatic efficacy at the radial access site of some chitosan-based hemostatic pads. This study aims to assess the efficacy and safety of a new chitosan-based hemostatic dressing, namely Axiostat^®, in aiding manual compression closure of the femoral arterial access site in patients undergoing endovascular treatments. Furthermore, the outcomes were compared with evidence on manual compression alone and vascular closure devices. Methods: This investigation is a two-center retrospective analysis of 120 consecutive patients who had undergone, from July 2022 to February 2023, manual compression closure of the femoral arterial access site aided by the Axiostat^® hemostatic dressing. Endovascular procedures performed with introducer sheaths ranging from 4 Fr to 8 Fr were evaluated. Results: Primary technical success was achieved in 110 (91.7%) patients, with adequate hemostasis obtained in all cases of prolonged manual compression requirements. The mean time-to-hemostasis and time-to-ambulation were 8.9 (±3.9) and 462 (±199) minutes, respectively. Clinical success was achieved in 113 (94.2%) patients, with bleeding-related complications noted in 7 (5.8%) patients. Conclusions: Manual compression aided by the Axiostat^® hemostatic dressing is effective and safe in achieving hemostasis of the femoral arterial access site in patients undergoing endovascular treatment with a 4–8 Fr introducer sheath. Full article

(This article belongs to the Special Issue Vascular Repair and Remodeling in Health and Disease)

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16 pages, 472 KB

Open AccessEditor’s ChoiceArticle

Association between Periodontitis Extent, Severity, and Progression Rate with Systemic Diseases and Smoking: A Retrospective Study

by Georgios S. Chatzopoulos, Ziou Jiang, Nicholas Marka and Larry F. Wolff

J. Pers. Med. 2023, 13(5), 814; https://doi.org/10.3390/jpm13050814 - 11 May 2023

Cited by 20 | Viewed by 4481

Abstract

Background: The aim of this study was to analyze the relationship between extent, severity (stage), and rate of progression (grade) of periodontitis with systemic diseases as well as smoking using a large database. Methods: Patients’ records identified in the BigMouth Dental Data Repository [...] Read more.

Background: The aim of this study was to analyze the relationship between extent, severity (stage), and rate of progression (grade) of periodontitis with systemic diseases as well as smoking using a large database. Methods: Patients’ records identified in the BigMouth Dental Data Repository with a periodontal diagnosis based on the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions were evaluated. Patients were further categorized based on extent, severity, and rate of progression. Data were extracted from patients’ electronic health records including demographic characteristics, dental procedural codes, and self-reported medical conditions, as well as the number of missing teeth. Results: A total of 2069 complete records were ultimately included in the analysis. Males were more likely to have generalized periodontitis and stage III or IV periodontitis. Older individuals were more likely diagnosed with grade B and stage III or IV periodontitis. Individuals with generalized disease, grade C, and stage IV demonstrated a significantly higher number of missing teeth. Higher numbers of tooth loss reported during supportive periodontal treatment were noted in generalized disease and stage IV periodontitis. Multiple sclerosis and smoking were significantly associated with grade C periodontitis. Conclusions: Within the limitations of this retrospective study that utilized the BigMouth dental data repository, smokers were significantly associated with rapid progression of periodontitis (grade C). Gender, age, number of missing teeth, and number of tooth loss during supportive periodontal treatment were associated with disease characteristics. Full article

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16 pages, 340 KB

Open AccessEditor’s ChoiceReview

Lung and Gut Microbiome in COPD

by Efstathios Karakasidis, Ourania S. Kotsiou and Konstantinos I. Gourgoulianis

J. Pers. Med. 2023, 13(5), 804; https://doi.org/10.3390/jpm13050804 - 8 May 2023

Cited by 27 | Viewed by 5074

Abstract

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. The association between lung and gut microbiomes in the pathogenesis of COPD has been recently uncovered. The goal of this study was to discuss the role of the lung [...] Read more.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. The association between lung and gut microbiomes in the pathogenesis of COPD has been recently uncovered. The goal of this study was to discuss the role of the lung and gut microbiomes in COPD pathophysiology. A systematic search of the PubMed database for relevant articles submitted up to June 2022 was performed. We examined the association between the lung and gut microbiome dysbiosis, reflected in bronchoalveolar lavage (BAL), lung tissue, sputum, and feces samples, and the pathogenesis and progression of COPD. It is evident that the lung and gut microbiomes affect each other and both play a vital role in the pathogenesis of COPD. However, more research needs to be carried out to find the exact associations between microbiome diversity and COPD pathophysiology and exacerbation genesis. Another field that research should focus on is the impact of treatment interventions targeting the human microbiome in preventing COPD genesis and progression. Full article

(This article belongs to the Section Personalized Therapy in Clinical Medicine)

13 pages, 916 KB

Open AccessEditor’s ChoiceArticle

Management of Onsite and Remote Communication in Oncology Hospitals: Data Protection in an Era of Rapid Technological Advances

by Mirosława Mocydlarz-Adamcewicz, Bartosz Bajsztok, Stanislav Filip, Jiri Petera, Miroslav Mestan and Julian Malicki

J. Pers. Med. 2023, 13(5), 761; https://doi.org/10.3390/jpm13050761 - 28 Apr 2023

Cited by 10 | Viewed by 2076

Abstract

Modern communication and information technologies are rapidly being deployed at health care institutions around the world. Although these technologies offer many benefits, ensuring data protection is a major concern, and implementation of robust data protection measures is essential. In this context, health care [...] Read more.

Modern communication and information technologies are rapidly being deployed at health care institutions around the world. Although these technologies offer many benefits, ensuring data protection is a major concern, and implementation of robust data protection measures is essential. In this context, health care providers and medical care facilities must frequently make difficult decisions and compromises between the need to provide effective medical care and the need to ensure data security and patient privacy. In the present paper, we describe and discuss key issues related to data protection systems in the setting of cancer care hospitals in Europe. We provide real-life examples from two European countries—Poland and the Czech Republic—to illustrate data protection issues and the steps being taking to address these questions. More specifically, we discuss the legal framework surrounding data protection and technical aspects related to patient authentication and communication. Full article

(This article belongs to the Special Issue Personalized Radiotherapy)

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16 pages, 2362 KB

Open AccessEditor’s ChoiceArticle

A New Detection Method of Oral and Oropharyngeal Squamous Cell Carcinoma Based on Multivariate Analysis of Surface Enhanced Raman Spectra of Salivary Exosomes

by Cosmin Ioan Faur, Cristian Dinu, Valentin Toma, Anca Jurj, Radu Mărginean, Anca Onaciu, Rareș Călin Roman, Carina Culic, Magdalena Chirilă, Horațiu Rotar, Alexandra Fălămaș, Gabriela Fabiola Știufiuc, Mihaela Hedeșiu, Oana Almășan and Rares Ionuț Știufiuc

J. Pers. Med. 2023, 13(5), 762; https://doi.org/10.3390/jpm13050762 - 28 Apr 2023

Cited by 21 | Viewed by 4810

Abstract

Raman spectroscopy recently proved a tremendous capacity to identify disease-specific markers in various (bio)samples being a non-invasive, rapid, and reliable method for cancer detection. In this study, we first aimed to record vibrational spectra of salivary exosomes isolated from oral and oropharyngeal squamous [...] Read more.

Raman spectroscopy recently proved a tremendous capacity to identify disease-specific markers in various (bio)samples being a non-invasive, rapid, and reliable method for cancer detection. In this study, we first aimed to record vibrational spectra of salivary exosomes isolated from oral and oropharyngeal squamous cell carcinoma patients and healthy controls using surface enhancement Raman spectroscopy (SERS). Then, we assessed this method’s capacity to discriminate between malignant and non-malignant samples by means of principal component–linear discriminant analysis (PC-LDA) and we used area under the receiver operating characteristics with illustration as the area under the curve to measure the power of salivary exosomes SERS spectra analysis to identify cancer presence. The vibrational spectra were collected on a solid plasmonic substrate developed in our group, synthesized using tangential flow filtered and concentrated silver nanoparticles, capable of generating very reproducible spectra for a whole range of bioanalytes. SERS examination identified interesting variations in the vibrational bands assigned to thiocyanate, proteins, and nucleic acids between the saliva of cancer and control groups. Chemometric analysis indicated discrimination sensitivity between the two groups up to 79.3%. The sensitivity is influenced by the spectral interval used for the multivariate analysis, being lower (75.9%) when the full-range spectra were used. Full article

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20 pages, 890 KB

Open AccessEditor’s ChoiceReview

Review of Endometrial Receptivity Array: A Personalized Approach to Embryo Transfer and Its Clinical Applications

by Sarah C. Rubin, Mawerdi Abdulkadir, Joshua Lewis, Aleksandr Harutyunyan, Rahim Hirani and Cara L. Grimes

J. Pers. Med. 2023, 13(5), 749; https://doi.org/10.3390/jpm13050749 - 27 Apr 2023

Cited by 23 | Viewed by 10528

Abstract

Successful outcomes of in vitro fertilization (IVF) rely on both the formation of a chromosomally normal embryo and its implantation in a receptive endometrium. Pre-implantation genetic testing for aneuploidy (PGT-A) has been widely accepted as a tool to assess the viability of an [...] Read more.

Successful outcomes of in vitro fertilization (IVF) rely on both the formation of a chromosomally normal embryo and its implantation in a receptive endometrium. Pre-implantation genetic testing for aneuploidy (PGT-A) has been widely accepted as a tool to assess the viability of an embryo. In 2011, the endometrial receptivity array (ERA) was first published as a tool to determine when the endometrium is most receptive to an embryo, commonly referred to as the “window of implantation” (WOI). The ERA uses molecular arrays to assess proliferation and differentiation in the endometrium and screens for inflammatory markers. Unlike PGT-A, there has been dissent within the field concerning the efficacy of the ERA. Many studies that contest the success of the ERA found that it did not improve pregnancy outcomes in patients with an already-good prognosis. Alternatively, studies that utilized the ERA in patients with repeated implantation failure (RIF) and transfer of known euploid embryos demonstrated improved outcomes. This review aims to describe the ERA as a novel technique, review the various settings that the ERA may be used in, such as natural frozen embryo transfer (nFET) and hormone replacement therapy frozen embryo transfer (HRT-FET), and provide a summary of the recent clinical data for embryo transfers in patients with RIF utilizing the ERA. Full article

(This article belongs to the Special Issue Precision Medicine in Reproductive Health)

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14 pages, 2087 KB

Open AccessEditor’s ChoiceReview

The Role of Cold Atmospheric Plasma in Wound Healing Processes in Critically Ill Patients

by Tatiana Bolgeo, Antonio Maconi, Menada Gardalini, Denise Gatti, Roberta Di Matteo, Marco Lapidari, Yaroslava Longhitano, Gabriele Savioli, Andrea Piccioni and Christian Zanza

J. Pers. Med. 2023, 13(5), 736; https://doi.org/10.3390/jpm13050736 - 26 Apr 2023

Cited by 42 | Viewed by 10231

Abstract

Critically ill patients are at risk of skin wounds, which reduce their quality of life, complicate their pharmacological regimens, and prolong their hospital stays in intensive care units (ICUs), while also increasing overall mortality and morbidity rates. Cold atmospheric plasma (CAP) has been [...] Read more.

Critically ill patients are at risk of skin wounds, which reduce their quality of life, complicate their pharmacological regimens, and prolong their hospital stays in intensive care units (ICUs), while also increasing overall mortality and morbidity rates. Cold atmospheric plasma (CAP) has been proposed as a viable option for many biological and medical applications, given its capacity to reduce wound bacterial contamination and promote wound healing. The aim of this narrative review is to describe how CAP works and its operating mechanisms, as well as reporting its possible applications in critical care settings. The success of CAP in the treatment of wounds, in particular, bedsores or pressure sores, presents an innovative path in the prevention of nosocomial infections and an opportunity of reducing the negative implications of these diseases for the NHS. This narrative review of the literature was conducted following the ‘Scale for the Assessment of Narrative Review Articles’ (SANRA) methodology. Previous literature highlights three biological effects of plasma: inactivation of a wide range of microorganisms, including those that are multi-drug-resistant; increased cell proliferation and angiogenesis with a shorter period of plasma treatment; and apoptosis stimulation with a longer and more intensive treatment. CAP is effective in many areas of the medical field, with no significant adverse effects on healthy cells. However, its use can produce potentially serious side effects and should, therefore, be used under expert supervision and in appropriate doses. Full article

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12 pages, 296 KB

Open AccessEditor’s ChoiceReview

Parathyroid Hormone (PTH)-Related Peptides Family: An Intriguing Role in the Central Nervous System

by Cristina Dettori, Francesca Ronca, Marco Scalese and Federica Saponaro

J. Pers. Med. 2023, 13(5), 714; https://doi.org/10.3390/jpm13050714 - 24 Apr 2023

Cited by 18 | Viewed by 6133

Abstract

Parathyroid Hormone (PTH) plays a crucial role in the maintenance of calcium homeostasis directly acting on bone and kidneys and indirectly on the intestine. However, a large family of PTH-related peptides exists that exerts other physiological effects on different tissues and organs, such [...] Read more.

Parathyroid Hormone (PTH) plays a crucial role in the maintenance of calcium homeostasis directly acting on bone and kidneys and indirectly on the intestine. However, a large family of PTH-related peptides exists that exerts other physiological effects on different tissues and organs, such as the Central Nervous System (CNS). In humans, PTH-related peptides are Parathyroid Hormone (PTH), PTH-like hormones (PTHrP and PTHLH), and tuberoinfundibular peptide of 39 (TIP39 or PTH2). With different affinities, these ligands can bind parathyroid receptor type 1 (PTH1R) and type 2 (PTH2R), which are part of the type II G-protein-coupled-receptors (GPCRs) family. The PTH/PTHrP/PTH1R system has been found to be expressed in many areas of the brain (hippocampus, amygdala, hypothalamus, caudate nucleus, corpus callosum, subthalamic nucleus, thalamus, substantia nigra, cerebellum), and literature data suggest the system exercises a protective action against neuroinflammation and neurodegeneration, with positive effects on memory and hyperalgesia. TIP39 is a small peptide belonging to the PTH-related family with a high affinity for PTH2R in the CNS. The TIP39/PTH2R system has been proposed to mediate many regulatory and functional roles in the brain and to modulate auditory, nociceptive, and sexual maturation functions. This review aims to summarize the knowledge of PTH-related peptides distribution and functions in the CNS and to highlight the gaps that still need to be filled. Full article

13 pages, 847 KB

Open AccessEditor’s ChoiceArticle

Possible Incidental Parkinson’s Disease following Asthma: A Nested Case–Control Study in Korea

by Mi Jung Kwon, Joo-Hee Kim, Ho Suk Kang, Hyun Lim, Min-Jeong Kim, Nan Young Kim, Se Hoon Kim, Hyo Geun Choi and Eun Soo Kim

J. Pers. Med. 2023, 13(5), 718; https://doi.org/10.3390/jpm13050718 - 24 Apr 2023

Cited by 5 | Viewed by 2753

Abstract

A connection between asthma and the occurrence of Parkinson’s disease (PD) has been suggested, but the findings have been contentious and require verification. In this nested case–control study using data from the Korean National Health Insurance Service—Health Screening Cohort (2002–2019), which comprised 9029 [...] Read more.

A connection between asthma and the occurrence of Parkinson’s disease (PD) has been suggested, but the findings have been contentious and require verification. In this nested case–control study using data from the Korean National Health Insurance Service—Health Screening Cohort (2002–2019), which comprised 9029 participants with PD and 36,116 matched controls, we explored the relationship between asthma and incident PD. An overlap-weighted logistic regression model was used to measure the probability of asthma and PD. After adjusting for various covariates, we found that asthma was related to a 1.11-fold greater probability of PD (95% confidence interval: 1.06–1.16). A subgroup analysis showed that this effect was independent of age, sex, residential area, or alcohol consumption, and that it was still noticeable even among patients with a high income; those with a normal weight or obesity; those who were non-smokers or current smokers; and those with no history of chronic obstructive pulmonary disease, hypertension, hyperglycemia, hyperlipidemia, or anemia. Thus, these findings may indicate that asthma may slightly augment the likelihood of PD in the Korean adult population regardless of demographic or lifestyle factors, making it difficult to predict PD in asthma patients. Full article

(This article belongs to the Special Issue Neuromuscular and Neurodegenerative Diseases: Towards Personalized Medicine, Therapeutics and Improved Mechanistic Understanding)

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15 pages, 987 KB

Open AccessEditor’s ChoiceReview

Modulation of Ferroptosis by microRNAs in Human Cancer

by Irena Velkova, Martina Pasino, Zumama Khalid, Paola Menichini, Emanuele Martorana, Alberto Izzotti and Alessandra Pulliero

J. Pers. Med. 2023, 13(5), 719; https://doi.org/10.3390/jpm13050719 - 24 Apr 2023

Cited by 16 | Viewed by 3721

Abstract

Ferroptosis is a cell death pathway triggered by an imbalance between the production of oxidants and antioxidants, which plays an emerging role in tumorigenesis. It is mainly regulated at three different levels including iron metabolism, the antioxidant response, and lipid metabolism. Epigenetic dysregulation [...] Read more.

Ferroptosis is a cell death pathway triggered by an imbalance between the production of oxidants and antioxidants, which plays an emerging role in tumorigenesis. It is mainly regulated at three different levels including iron metabolism, the antioxidant response, and lipid metabolism. Epigenetic dysregulation is a “hallmark” of human cancer, with nearly half of all human cancers harboring mutations in epigenetic regulators such as microRNA. While being the crucial player in controlling gene expression at the mRNA level, microRNAs have recently been shown to modulate cancer growth and development via the ferroptosis pathway. In this scenario, some miRNAs have a function in upregulating, while others play a role in inhibiting ferroptosis activity. The investigation of validated targets using the miRBase, miRTarBase, and miRecords platforms identified 13 genes that appeared enriched for iron metabolism, lipid peroxidation, and antioxidant defense; all are recognized contributors of tumoral suppression or progression phenotypes. This review summarizes and discuss the mechanism by which ferroptosis is initiated through an imbalance in the three pathways, the potential function of microRNAs in the control of this process, and a description of the treatments that have been shown to have an impact on the ferroptosis in cancer along with potential novel effects. Full article

(This article belongs to the Section Personalized Therapy in Clinical Medicine)

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20 pages, 1875 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Impact of Hypothermic Oxygenated Machine Perfusion on Hepatocellular Carcinoma Recurrence after Liver Transplantation

by Federica Rigo, Nicola De Stefano, Damiano Patrono, Victor De Donato, Ludovico Campi, Diana Turturica, Teresa Doria, Veronica Sciannameo, Paola Berchialla, Francesco Tandoi and Renato Romagnoli

J. Pers. Med. 2023, 13(5), 703; https://doi.org/10.3390/jpm13050703 - 22 Apr 2023

Cited by 16 | Viewed by 2458

Abstract

Background: Machine perfusion may be able to mitigate ischemia-reperfusion injury (IRI), which increases hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). This study aimed to investigate the impact of dual-hypothermic oxygenated machine perfusion (D-HOPE) on HCC recurrence in LT. Methods: A single-center retrospective [...] Read more.

Background: Machine perfusion may be able to mitigate ischemia-reperfusion injury (IRI), which increases hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). This study aimed to investigate the impact of dual-hypothermic oxygenated machine perfusion (D-HOPE) on HCC recurrence in LT. Methods: A single-center retrospective study was conducted from 2016 to 2020. Pre- and postoperative data of HCC patients undergoing LT were analyzed. Recipients of a D-HOPE-treated graft were compared to those of livers preserved using static cold storage (SCS). The primary endpoint was recurrence-free survival (RFS). Results: Of 326 patients, 246 received an SCS-preserved liver and 80 received a D-HOPE-treated graft (donation after brain death (DBD), n = 66; donation after circulatory death (DCD), n = 14). Donors of D-HOPE-treated grafts were older and had higher BMI. All DCD donors were treated by normothermic regional perfusion and D-HOPE. The groups were comparable in terms of HCC features and estimated 5-year RFS according to the Metroticket 2.0 model. D-HOPE did not reduce HCC recurrence (D-HOPE 10%; SCS 8.9%; p = 0.95), which was confirmed using Bayesian model averaging and inverse probability of treatment weighting-adjusted RFS analysis. Postoperative outcomes were comparable between groups, except for lower AST and ALT peak in the D-HOPE group. Conclusions: In this single-center study, D-HOPE did not reduce HCC recurrence but allowed utilizing livers from extended criteria donors with comparable outcomes, improving access to LT for patients suffering from HCC. Full article

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19 pages, 811 KB

Open AccessEditor’s ChoiceSystematic Review

Investigating the Role of Maintenance TMS Protocols for Major Depression: Systematic Review and Future Perspectives for Personalized Interventions

by Giacomo d’Andrea, Gianluca Mancusi, Maria Chiara Santovito, Carlotta Marrangone, Fabrizio Martino, Mario Santorelli, Andrea Miuli, Francesco Di Carlo, Maria Salvina Signorelli, Massimo Clerici, Mauro Pettorruso and Giovanni Martinotti

J. Pers. Med. 2023, 13(4), 697; https://doi.org/10.3390/jpm13040697 - 21 Apr 2023

Cited by 32 | Viewed by 8242

Abstract

Repetitive Transcranial Magnetic Stimulation (rTMS) has been approved by the FDA as an effective intervention for Treatment-Resistant Depression (TRD). However, there is little evidence about maintenance protocol necessity. The aim of this systematic review is to identify, characterize, and evaluate the current maintenance [...] Read more.

Repetitive Transcranial Magnetic Stimulation (rTMS) has been approved by the FDA as an effective intervention for Treatment-Resistant Depression (TRD). However, there is little evidence about maintenance protocol necessity. The aim of this systematic review is to identify, characterize, and evaluate the current maintenance TMS protocols for MDD and TRD patients who have received acute treatment. A literature search was conducted following the PRISMA guidelines of 2015 on PubMed, Scopus, and Web of Science databases for publications up to March 2022. Fourteen articles were included. High protocol heterogeneity was observed. Most studies highlighted significant efficacy of maintenance protocols in decreasing relapse risk, suggesting that administering two or fewer stimulations per month is ineffective in sustaining an antidepressant effect or in reducing the risk of relapse in responder patients. The risk of relapse was most pronounced after five months from the acute treatment. Maintenance TMS appears to be a resourceful strategy to maintain acute antidepressant treatment effects, significantly reducing relapse risk. The ease of administering and the ability to monitor treatment adherence should be considered when evaluating the future use of maintenance TMS protocols. Further studies are needed to clarify the clinical relevance of overlapping acute TMS effects with maintenance protocols and to evaluate their long-term effectiveness. Full article

(This article belongs to the Special Issue Biomarkers in Psychiatric Disorders)

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12 pages, 3998 KB

Open AccessEditor’s ChoiceArticle

Radiation Exposure and Frequency of Dental, Bitewing and Occlusal Radiographs in Children and Adolescents

by Ina Manuela Schüler, Christoph-Ludwig Hennig, Rika Buschek, Rebecca Scherbaum, Collin Jacobs, Marcel Scheithauer and Hans-Joachim Mentzel

J. Pers. Med. 2023, 13(4), 692; https://doi.org/10.3390/jpm13040692 - 20 Apr 2023

Cited by 16 | Viewed by 11414

Abstract

Dental radiographs are valuable diagnostic aids for oral healthcare, but exposure to ionizing radiation carries health risks, especially in children due to their high radio-sensitivity. Valid reference values for intraoral radiographs in children and adolescents are still missing. This study aimed to investigate [...] Read more.

Dental radiographs are valuable diagnostic aids for oral healthcare, but exposure to ionizing radiation carries health risks, especially in children due to their high radio-sensitivity. Valid reference values for intraoral radiographs in children and adolescents are still missing. This study aimed to investigate the radiation dose values and underlying justifications of dental, bitewing and occlusal X-rays in children and adolescents. Data from routinely executed intraoral radiographs between 2002 and 2020 with conventional and digital tube-heads were extracted from the Radiology Information System. The effective exposure was calculated from technical parameters and statistical tests performed. A total number of 4455 intraoral (3128 dental, 903 bitewing and 424 occlusal) radiographs were investigated. For dental and bitewing radiographs, the dose area product (DAP) was 2.57 cGy × cm² and the effective dose (ED) 0.77 µSv. For occlusal radiographs, the DAP was 7.43 cGy × cm² and the ED 2.22 µSv. Overall, 70.2% of all intraoral radiographs were dental, 20.3% bitewing and 9.5% occlusal radiographs. The most frequent indication for intraoral radiographs was trauma (28.7%), followed by caries (22.7%) and apical diagnostics (22.7%). Moreover, 59.7% of all intraoral radiographs were taken in boys, especially for trauma (66.5%) and endodontics (67.2%) (p ≤ 0.00). Girls were significantly more frequently X-rayed for caries diagnostics than boys (28.1% vs. 19.1%, p ≤ 0.00). The average ED of 0.77 µSv for intraoral dental and bitewing radiographs in this study was within the range of other reported values. The technical parameters of the X-ray devices were found at the lowest recommended levels to best limit the radiation exposure and to assure acceptable diagnostic efficacy. Intraoral radiographs were performed predominantly for trauma, caries and apical diagnostics—reflecting general recommendations for the use of X-rays in children. For improved quality assurance and radiation protection, further studies are necessary to determine the meaningful dose reference level (DRL) for children. Full article

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19 pages, 349 KB

Open AccessEditor’s ChoiceReview

Utilization of Circulating Tumor Cells in the Management of Solid Tumors

by Peter C. Kurniali, Michael H. Storandt and Zhaohui Jin

J. Pers. Med. 2023, 13(4), 694; https://doi.org/10.3390/jpm13040694 - 20 Apr 2023

Cited by 8 | Viewed by 3281

Abstract

Circulating tumor cells (CTCs) are tumor cells shed from the primary tumor into circulation, with clusters of CTCs responsible for cancer metastases. CTC detection and isolation from the bloodstream are based on properties distinguishing CTCs from normal blood cells. Current CTC detection techniques [...] Read more.

Circulating tumor cells (CTCs) are tumor cells shed from the primary tumor into circulation, with clusters of CTCs responsible for cancer metastases. CTC detection and isolation from the bloodstream are based on properties distinguishing CTCs from normal blood cells. Current CTC detection techniques can be divided into two main categories: label dependent, which depends upon antibodies that selectively bind cell surface antigens present on CTCs, or label-independent detection, which is detection based on the size, deformability, and biophysical properties of CTCs. CTCs may play significant roles in cancer screening, diagnosis, treatment navigation, including prognostication and precision medicine, and surveillance. In cancer screening, capturing and evaluating CTCs from peripheral blood could be a strategy to detect cancer at its earliest stage. Cancer diagnosis using liquid biopsy could also have tremendous benefits. Full utilization of CTCs in the clinical management of malignancies may be feasible in the near future; however, several challenges still exist. CTC assays currently lack adequate sensitivity, especially in early-stage solid malignancies, due to low numbers of detectable CTCs. As assays improve and more trials evaluate the clinical utility of CTC detection in guiding therapies, we anticipate increased use in cancer management. Full article

15 pages, 3672 KB

Open AccessEditor’s ChoiceArticle

Needs and Demands for eHealth Pain Management Interventions in Chronic Pain Patients

by Paula Stoppok, Anna-Lena Frewer, Adam Schweda, Sheila Geiger, Eva-Maria Skoda, Diana Müßgens, Ulrike Bingel, Martin Teufel and Alexander Bäuerle

J. Pers. Med. 2023, 13(4), 675; https://doi.org/10.3390/jpm13040675 - 17 Apr 2023

Cited by 9 | Viewed by 2905

Abstract

Although chronic pain is a global health problem, the current care situation is often inadequate. eHealth offers many advantages as an additional option for treating chronic pain. Yet, an intervention’s efficacy can only be fully exhausted if patients intend to use it. This [...] Read more.

Although chronic pain is a global health problem, the current care situation is often inadequate. eHealth offers many advantages as an additional option for treating chronic pain. Yet, an intervention’s efficacy can only be fully exhausted if patients intend to use it. This study aims to identify the needs and demands of patients with chronic pain regarding intervention concepts and frameworks to develop specifically tailored eHealth pain management interventions. A cross-sectional study was conducted, including 338 individuals with chronic pain. Within the cohort, a distinction between a high- and a low-burden group was made. Respondents generally preferred a permanently accompanying mobile app, but the preferred content varied with group. According to the majority, interventions should be made available on smartphones, offer sessions once per week with a duration from 10 to 30 min, and be recommended by experts. These results can provide the basis for future eHealth pain management interventions tailored to the patients’ needs and demands. Full article

(This article belongs to the Special Issue Personalized Therapy and Clinical Outcomes for Chronic Pain)

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25 pages, 1615 KB

Open AccessEditor’s ChoiceReview

The Role of BDNF as a Biomarker in Cognitive and Sensory Neurodegeneration

by Anna Pisani, Fabiola Paciello, Valeria Del Vecchio, Rita Malesci, Eugenio De Corso, Elena Cantone and Anna Rita Fetoni

J. Pers. Med. 2023, 13(4), 652; https://doi.org/10.3390/jpm13040652 - 10 Apr 2023

Cited by 72 | Viewed by 11484

Abstract

Brain-derived neurotrophic factor (BDNF) has a crucial function in the central nervous system and in sensory structures including olfactory and auditory systems. Many studies have highlighted the protective effects of BDNF in the brain, showing how it can promote neuronal growth and survival [...] Read more.

Brain-derived neurotrophic factor (BDNF) has a crucial function in the central nervous system and in sensory structures including olfactory and auditory systems. Many studies have highlighted the protective effects of BDNF in the brain, showing how it can promote neuronal growth and survival and modulate synaptic plasticity. On the other hand, conflicting data about BDNF expression and functions in the cochlear and in olfactory structures have been reported. Several clinical and experimental research studies showed alterations in BDNF levels in neurodegenerative diseases affecting the central and peripheral nervous system, suggesting that BDNF can be a promising biomarker in most neurodegenerative conditions, including Alzheimer’s disease, shearing loss, or olfactory impairment. Here, we summarize current research concerning BDNF functions in brain and in sensory domains (olfaction and hearing), focusing on the effects of the BDNF/TrkB signalling pathway activation in both physiological and pathological conditions. Finally, we review significant studies highlighting the possibility to target BDNF as a biomarker in early diagnosis of sensory and cognitive neurodegeneration, opening new opportunities to develop effective therapeutic strategies aimed to counteract neurodegeneration. Full article

(This article belongs to the Section Personalized Therapy in Clinical Medicine)

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18 pages, 492 KB

Open AccessEditor’s ChoiceSystematic Review

Is Ozone a Valid Adjuvant Therapy for Periodontitis and Peri-Implantitis? A Systematic Review

by Francesco D′Ambrosio, Mario Caggiano, Alfonso Acerra, Massimo Pisano and Francesco Giordano

J. Pers. Med. 2023, 13(4), 646; https://doi.org/10.3390/jpm13040646 - 8 Apr 2023

Cited by 27 | Viewed by 5235

Abstract

Introduction: Ozone is a naturally occurring unstable compound with three oxygen atoms that generally transforms into an oxygen molecule, releasing one oxygen atom. This feature has been exploited in dentistry for numerous applications, including for periodontal diseases and peri-implantitis. Methods: This review was [...] Read more.

Introduction: Ozone is a naturally occurring unstable compound with three oxygen atoms that generally transforms into an oxygen molecule, releasing one oxygen atom. This feature has been exploited in dentistry for numerous applications, including for periodontal diseases and peri-implantitis. Methods: This review was performed in relation to the PRISMA flow chart and was annotated in the PROSPERO register. PICO questions were used as research questions. The risk of bias in the non-randomized clinical trials was appraised using the ROBINS-I tool. Results: An electronic search found a total of 1073 records, in particular, 842 from MEDLINE/PubMed, 13 from Bio Med Central, 160 from Scopus, 1 from the Cochrane library databases, and 57 from the PROSPERO register. A total of 17 studies were included in the present systematic review. Information regarding the characteristics of the periodontal clinical and radiographic parameters for gaseous ozone, ozonate water, ozonate oil, and ozone gel, including clinical attachment loss (CAL) probing depth (PPD), bleeding on probing (BoP), plaque index (PI), gingival index (GI), and marginal bone levels (MBL), were obtained. Conclusions: The studies included in this systematic review show different results regarding the ozone in periodontal treatment in association with or without SRP. Full article

(This article belongs to the Section Mechanisms of Diseases)

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16 pages, 2896 KB

Open AccessEditor’s ChoiceArticle

Efficacy and Safety of Distal Radial Access for Transcatheter Arterial Chemoembolization (TACE) of the Liver

by Roberto Minici, Raffaele Serra, Marco Giurdanella, Marisa Talarico, Maria Anna Siciliano, Gianpaolo Carrafiello and Domenico Laganà

J. Pers. Med. 2023, 13(4), 640; https://doi.org/10.3390/jpm13040640 - 7 Apr 2023

Cited by 22 | Viewed by 4713

Abstract

Background: The distal radial artery has emerged as an alternative vascular-access site to conventional transfemoral and transradial approaches. The main advantage over the conventional transradial route is the reduced risk of radial artery occlusion, especially in those patients who, for various clinical reasons, [...] Read more.

Background: The distal radial artery has emerged as an alternative vascular-access site to conventional transfemoral and transradial approaches. The main advantage over the conventional transradial route is the reduced risk of radial artery occlusion, especially in those patients who, for various clinical reasons, have to undergo repeated endovascular procedures. This study aims to assess the efficacy and safety of distal radial access for transcatheter arterial chemoembolization of the liver. Methods: This investigation is a single-center retrospective analysis of 42 consecutive patients who had undergone, from January 2018 to December 2022, transcatheter arterial chemoembolization of the liver with distal radial access for intermediate-stage hepatocellular carcinoma. Outcome data were compared with a retrospectively constituted control group of 40 patients undergoing drug-eluting beads-transcatheter arterial chemoembolization with femoral access. Results: Technical success was achieved in all cases, with a 2.4% conversion rate for distal radial access. A superselective chemoembolization was performed in 35 (83.3%) cases of distal radial access. No episode of radial artery spasm or radial artery occlusion occurred. No significant differences in efficacy and safety were observed between the distal radial access group and the femoral access group. Conclusions: Distal radial access is effective, safe, and comparable to femoral access in patients undergoing transcatheter arterial chemoembolization of the liver. Full article

(This article belongs to the Special Issue Vascular Repair and Remodeling in Health and Disease)

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16 pages, 293 KB

Open AccessEditor’s ChoiceReview

Active Surveillance for Prostate Cancer: Past, Current, and Future Trends

by Ivo I. de Vos, Henk B. Luiting and Monique J. Roobol

J. Pers. Med. 2023, 13(4), 629; https://doi.org/10.3390/jpm13040629 - 3 Apr 2023

Cited by 38 | Viewed by 7493

Abstract

In response to the rising incidence of indolent, low-risk prostate cancer (PCa) due to increased prostate-specific antigen (PSA) screening in the 1990s, active surveillance (AS) emerged as a treatment modality to combat overtreatment by delaying or avoiding unnecessary definitive treatment and its associated [...] Read more.

In response to the rising incidence of indolent, low-risk prostate cancer (PCa) due to increased prostate-specific antigen (PSA) screening in the 1990s, active surveillance (AS) emerged as a treatment modality to combat overtreatment by delaying or avoiding unnecessary definitive treatment and its associated morbidity. AS consists of regular monitoring of PSA levels, digital rectal exams, medical imaging, and prostate biopsies, so that definitive treatment is only offered when deemed necessary. This paper provides a narrative review of the evolution of AS since its inception and an overview of its current landscape and challenges. Although AS was initially only performed in a study setting, numerous studies have provided evidence for the safety and efficacy of AS which has led guidelines to recommend it as a treatment option for patients with low-risk PCa. For intermediate-risk disease, AS appears to be a viable option for those with favourable clinical characteristics. Over the years, the inclusion criteria, follow-up schedule and triggers for definitive treatment have evolved based on the results of various large AS cohorts. Given the burdensome nature of repeat biopsies, risk-based dynamic monitoring may further reduce overtreatment by avoiding repeat biopsies in selected patients. Full article

11 pages, 1240 KB

Open AccessEditor’s ChoiceArticle

Prognostic Value of Malondialdehyde (MDA) in the Temporal Progression of Chronic Spinal Cord Injury

by Sergio Haro Girón, Jorge Monserrat Sanz, Miguel A. Ortega, Cielo Garcia-Montero, Oscar Fraile-Martínez, Ana M. Gómez-Lahoz, Diego Liviu Boaru, Diego de Leon-Oliva, Luis G. Guijarro, Mar Atienza-Perez, David Diaz, Elisa Lopez-Dolado and Melchor Álvarez-Mon

J. Pers. Med. 2023, 13(4), 626; https://doi.org/10.3390/jpm13040626 - 2 Apr 2023

Cited by 33 | Viewed by 4495

Abstract

Background: Oxidative stress is a major signature of spinal cord injury (SCI). The altered levels of various oxidative stress markers have been demonstrated in acute and chronic SCI. However, the variation of these markers in patients with chronic SCI depending on the time [...] Read more.

Background: Oxidative stress is a major signature of spinal cord injury (SCI). The altered levels of various oxidative stress markers have been demonstrated in acute and chronic SCI. However, the variation of these markers in patients with chronic SCI depending on the time since the initial injury has not been explored yet. Objective: Our aim was to measure plasma levels of malondialdehyde (MDA), a marker of lipid peroxidation in patients with SCI stratified in different periods of suffering the injury (0–5 years, 5–10 years, and more than 10 years). Patients and methods: This cross-sectional study enrolled patients with SCI (N = 105) from different periods of the lesion and healthy control (HC) subjects (N = 38): short period (SCI SP, N = 31, time of evolution less than 5 years); early chronic (SCI ECP, N = 32, time of evolution 5–15 years); and late chronic (SCI LCP, N = 42, time of evolution more than 15 years). The plasma levels of MDA were measured using a commercially available colorimetric assay. Results: Patients with SCI had significantly higher plasma levels of MDA than HC subjects. Receiver operating characteristic (ROC) curve analysis for plasma MDA levels in patients with SCI demonstrated areas under the curve (AUC) of 1 (HC vs. SCI-SP); 0.998 (HC vs. SCI-ECP); and 0.964 (HC vs. SCI-LCP). Additionally, three ROC curves were used to compare the different concentrations of MDA between the subgroups of patients with SCI, and the resulting AUCs were: 0.896 (SCI-SP vs. SCI-ECP); 0.840 (SCI-ECP vs. SCI-LCP); and 0.979 (SCI-SP vs. SCI-LCP). Conclusion: Plasma concentration of MDA can be considered as an oxidative stress biomarker to assess the prognosis of SCI in chronic stages. Full article

(This article belongs to the Section Mechanisms of Diseases)

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13 pages, 270 KB

Open AccessEditor’s ChoiceReview

State of the Art and Challenges in Epilepsy—A Narrative Review

by Aida Mihaela Manole, Carmen Adella Sirbu, Mihaela Raluca Mititelu, Octavian Vasiliu, Lorenzo Lorusso, Octavian Mihai Sirbu and Florentina Ionita Radu

J. Pers. Med. 2023, 13(4), 623; https://doi.org/10.3390/jpm13040623 - 1 Apr 2023

Cited by 32 | Viewed by 9034

Abstract

Epilepsy is a common condition worldwide, with approximately 50 million people suffering from it. A single seizure does not mean epilepsy; almost 10% of the population can have a seizure during their lifetime. In particular, there are many other central nervous system disorders [...] Read more.

Epilepsy is a common condition worldwide, with approximately 50 million people suffering from it. A single seizure does not mean epilepsy; almost 10% of the population can have a seizure during their lifetime. In particular, there are many other central nervous system disorders other than epilepsy in which seizures occur, either transiently or as a comorbid condition. The impact of seizures and epilepsy is, therefore, widespread and easily underestimated. It is estimated that about 70% of patients with epilepsy could be seizure-free if correctly diagnosed and treated. However, for patients with epilepsy, quality of life is influenced not only by seizure control but also by antiepileptic drug-adverse reactions, access to education, mood, employment, and transportation. Full article

(This article belongs to the Special Issue Epilepsy: Pathogenesis, Treatment, and Precision Medicine)

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Open AccessEditor’s ChoiceArticle

Breast Density Evaluation According to BI-RADS 5th Edition on Digital Breast Tomosynthesis: AI Automated Assessment Versus Human Visual Assessment

by Daniele Ugo Tari, Rosalinda Santonastaso, Davide Raffaele De Lucia, Marika Santarsiere and Fabio Pinto

J. Pers. Med. 2023, 13(4), 609; https://doi.org/10.3390/jpm13040609 - 30 Mar 2023

Cited by 14 | Viewed by 6260

Abstract

Background: The assessment of breast density is one of the main goals of radiologists because the masking effect of dense fibroglandular tissue may affect the mammographic identification of lesions. The BI-RADS 5th Edition has revised the mammographic breast density categories, focusing on a [...] Read more.

Background: The assessment of breast density is one of the main goals of radiologists because the masking effect of dense fibroglandular tissue may affect the mammographic identification of lesions. The BI-RADS 5th Edition has revised the mammographic breast density categories, focusing on a qualitative evaluation rather than a quantitative one. Our purpose is to compare the concordance of the automatic classification of breast density with the visual assessment according to the latest available classification. Methods: A sample of 1075 digital breast tomosynthesis images from women aged between 40 and 86 years (58 ± 7.1) was retrospectively analyzed by three independent readers according to the BI-RADS 5th Edition. Automated breast density assessment was performed on digital breast tomosynthesis images with the Quantra software version 2.2.3. Interobserver agreement was assessed with kappa statistics. The distributions of breast density categories were compared and correlated with age. Results: The agreement on breast density categories was substantial to almost perfect between radiologists (κ = 0.63–0.83), moderate to substantial between radiologists and the Quantra software (κ = 0.44–0.78), and the consensus of radiologists and the Quantra software (κ = 0.60–0.77). Comparing the assessment for dense and non-dense breasts, the agreement was almost perfect in the screening age range without a statistically significant difference between concordant and discordant cases when compared by age. Conclusions: The categorization proposed by the Quantra software has shown a good agreement with the radiological evaluations, even though it did not completely reflect the visual assessment. Thus, clinical decisions regarding supplemental screening should be based on the radiologist’s perceived masking effect rather than the data produced exclusively by the Quantra software. Full article

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

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12 pages, 1677 KB

Open AccessEditor’s ChoiceArticle

Baseline CTC Count as a Predictor of Long-Term Outcomes in High-Risk Prostate Cancer

by Wojciech A. Cieślikowski, Piotr Milecki, Monika Świerczewska, Agnieszka Ida, Michał Kasperczak, Agnieszka Jankowiak, Michał Nowicki, Klaus Pantel, Catherine Alix-Panabières, Maciej Zabel, Andrzej Antczak and Joanna Budna-Tukan

J. Pers. Med. 2023, 13(4), 608; https://doi.org/10.3390/jpm13040608 - 30 Mar 2023

Cited by 11 | Viewed by 2960

Abstract

The aim of the present study was to verify whether the baseline circulating tumor cell (CTC) count might serve as a predictor of overall survival (OS) and metastasis-free survival (MFS) in patients with high-risk prostate cancer (PCa) during a follow-up period of at [...] Read more.

The aim of the present study was to verify whether the baseline circulating tumor cell (CTC) count might serve as a predictor of overall survival (OS) and metastasis-free survival (MFS) in patients with high-risk prostate cancer (PCa) during a follow-up period of at least 5 years. CTCs were enumerated using three different assay formats in 104 patients: the CellSearch^® system, EPISPOT assay and GILUPI CellCollector. A total of 57 (55%) patients survived until the end of the follow-up period, with a 5 year OS of 66% (95% CI: 56–74%). The analysis of univariate Cox proportional hazard models identified a baseline CTC count ≥ 1, which was determined with the CellSearch^® system, a Gleason sum ≥ 8, cT ≥ 2c and metastases at initial diagnosis as significant predictors of a worse OS in the entire cohort. The CTC count ≥ 1 was also the only significant predictor of a worse OS in a subset of 85 patients who presented with localized PCa at the baseline. The baseline CTC number did not affect the MFS. In conclusion, the baseline CTC count can be considered a determinant of survival in high-risk PCa and also in patients with a localized disease. However, determining the prognostic value of the CTC count in patients with localized PCa would optimally require longitudinal monitoring of this parameter. Full article

(This article belongs to the Section Personalized Therapy in Clinical Medicine)

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13 pages, 526 KB

Open AccessEditor’s ChoiceArticle

Strategies of Endoscopic Management of Upper Tract Urothelial Carcinoma among Endourologists: A Global Survey

by Asaf Shvero, Orel Carmona, Dorit E. Zilberman, Zohar A. Dotan, Miki Haifler and Nir Kleinmann

J. Pers. Med. 2023, 13(4), 591; https://doi.org/10.3390/jpm13040591 - 28 Mar 2023

Cited by 5 | Viewed by 1948

Abstract

Up-to-date guidelines on the management of upper tract urothelial carcinoma (UTUC) are continuously published. We aim to assess the variability of diagnosis and treatment strategies in the endoscopic management of UTUC and adherence to European Association of Urology and National Comprehensive Cancer Network [...] Read more.

Up-to-date guidelines on the management of upper tract urothelial carcinoma (UTUC) are continuously published. We aim to assess the variability of diagnosis and treatment strategies in the endoscopic management of UTUC and adherence to European Association of Urology and National Comprehensive Cancer Network guidelines. A 15-question survey was designed to query practitioners on approaches to clinical practice and knowledge about endoscopic treatment indications and techniques. It was emailed to all members of the Endourologic Society through the society’s office, and to all Israeli non-member endourologists. Eighty-eight urologists participated in the survey. Adherence to guidelines on indications for endoscopic management was only 51%. Most of the survey respondents (87.5%) use holmium laser for tumor ablation, and ~50% use forceps for biopsy while the other half use baskets. Only 50% stated that they would use Jelmyto^® for specific indications. Most (80%) indicated that they repeat the ureteroscopy 3 months after the first one, and 52.3% continue with follow-up ureteroscopy every 3 months during the first year after diagnosis. There is vast variability among endourologists in the technical aspects of UTUC, the indications for endoscopic management, and adherence to the available guidelines for managing UTUC. Full article

(This article belongs to the Section Personalized Therapy in Clinical Medicine)

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14 pages, 1495 KB

Open AccessEditor’s ChoiceReview

Patient Self-Inflicted Lung Injury—A Narrative Review of Pathophysiology, Early Recognition, and Management Options

by Peter Sklienka, Michal Frelich and Filip Burša

J. Pers. Med. 2023, 13(4), 593; https://doi.org/10.3390/jpm13040593 - 28 Mar 2023

Cited by 26 | Viewed by 12346

Abstract

Patient self-inflicted lung injury (P-SILI) is a life-threatening condition arising from excessive respiratory effort and work of breathing in patients with lung injury. The pathophysiology of P-SILI involves factors related to the underlying lung pathology and vigorous respiratory effort. P-SILI might develop both [...] Read more.

Patient self-inflicted lung injury (P-SILI) is a life-threatening condition arising from excessive respiratory effort and work of breathing in patients with lung injury. The pathophysiology of P-SILI involves factors related to the underlying lung pathology and vigorous respiratory effort. P-SILI might develop both during spontaneous breathing and mechanical ventilation with preserved spontaneous respiratory activity. In spontaneously breathing patients, clinical signs of increased work of breathing and scales developed for early detection of potentially harmful effort might help clinicians prevent unnecessary intubation, while, on the contrary, identifying patients who would benefit from early intubation. In mechanically ventilated patients, several simple non-invasive methods for assessing the inspiratory effort exerted by the respiratory muscles were correlated with respiratory muscle pressure. In patients with signs of injurious respiratory effort, therapy aimed to minimize this problem has been demonstrated to prevent aggravation of lung injury and, therefore, improve the outcome of such patients. In this narrative review, we accumulated the current information on pathophysiology and early detection of vigorous respiratory effort. In addition, we proposed a simple algorithm for prevention and treatment of P-SILI that is easily applicable in clinical practice. Full article

(This article belongs to the Special Issue Precision Medicine for Acute Respiratory Distress Syndrome (ARDS))

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14 pages, 1864 KB

Open AccessEditor’s ChoiceArticle

Use, Abuse, and Misuse of Nasal Medications: Real-Life Survey on Community Pharmacist’s Perceptions

by Elena Russo, Francesco Giombi, Giovanni Paoletti, Enrico Heffler, Giorgio Walter Canonica, Francesca Pirola, Giuseppe Mercante, Giuseppe Spriano, Luca Malvezzi, Enrico Keber, SGCP and Corrado Giua

J. Pers. Med. 2023, 13(4), 579; https://doi.org/10.3390/jpm13040579 - 26 Mar 2023

Cited by 13 | Viewed by 6563

Abstract

Background: Medication overuse is an increasing global problem, especially for those rhinology diseases whose management requires over-the-counter drugs. This observational community pharmacy-based study aimed to investigate the actual use of the best-selling topical nasal medications and to characterize the clinical issues underlying their [...] Read more.

Background: Medication overuse is an increasing global problem, especially for those rhinology diseases whose management requires over-the-counter drugs. This observational community pharmacy-based study aimed to investigate the actual use of the best-selling topical nasal medications and to characterize the clinical issues underlying their query through the pharmacist’s perception. Methods: In the pilot phase, a preliminary survey was developed by a team of researchers and tested on a small sample of practitioners to assess usability and intelligibility. Eventual amendments were made according to the feedback obtained, and the final version was submitted to practitioners working in 376 pharmacies evenly distributed over the Italian territory. Results: Two groups of customers (18–30 years old and 60–75 years old) were the ones who most frequently purchased topical decongestants. The dosage applied for sympathomimetic amines was higher than recommended in up to 44.4% and the duration of use longer than 5 days in up to 31.9% of the cases. Patients’ queries of alpha agonists and topical corticosteroids resulted in significantly higher numbers than practitioners’ prescriptions. Allergic rhinitis was the most common disease affecting patients seeking sympathomimetic amines. Conclusions: The prolonged use of sympathomimetic amines in patients suffering from rhinology diseases is a significant problem that requires greater attention in terms of social education and surveillance. Full article

(This article belongs to the Special Issue Recent Advances in Diagnosis, Treatment and Observation in Otorhinolaryngology)

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12 pages, 1814 KB

Open AccessEditor’s ChoiceArticle

Generative Adversarial Networks Can Create High Quality Artificial Prostate Cancer Magnetic Resonance Images

by Isaac R. L. Xu, Derek J. Van Booven, Sankalp Goberdhan, Adrian Breto, Joao Porto, Mohammad Alhusseini, Ahmad Algohary, Radka Stoyanova, Sanoj Punnen, Anton Mahne and Himanshu Arora

J. Pers. Med. 2023, 13(3), 547; https://doi.org/10.3390/jpm13030547 - 18 Mar 2023

Cited by 13 | Viewed by 5029

Abstract

The recent integration of open-source data with machine learning models, especially in the medical field, has opened new doors to studying disease progression and/or regression. However, the ability to use medical data for machine learning approaches is limited by the specificity of data [...] Read more.

The recent integration of open-source data with machine learning models, especially in the medical field, has opened new doors to studying disease progression and/or regression. However, the ability to use medical data for machine learning approaches is limited by the specificity of data for a particular medical condition. In this context, the most recent technologies, like generative adversarial networks (GANs), are being looked upon as a potential way to generate high-quality synthetic data that preserve the clinical variability of a condition. However, despite some success, GAN model usage remains largely minimal when depicting the heterogeneity of a disease such as prostate cancer. Previous studies from our group members have focused on automating the quantitative multi-parametric magnetic resonance imaging (mpMRI) using habitat risk scoring (HRS) maps on the prostate cancer patients in the BLaStM trial. In the current study, we aimed to use the images from the BLaStM trial and other sources to train the GAN models, generate synthetic images, and validate their quality. In this context, we used T2-weighted prostate MRI images as training data for Single Natural Image GANs (SinGANs) to make a generative model. A deep learning semantic segmentation pipeline trained the model to segment the prostate boundary on 2D MRI slices. Synthetic images with a high-level segmentation boundary of the prostate were filtered and used in the quality control assessment by participating scientists with varying degrees of experience (more than ten years, one year, or no experience) to work with MRI images. Results showed that the most experienced participating group correctly identified conventional vs. synthetic images with 67% accuracy, the group with one year of experience correctly identified the images with 58% accuracy, and the group with no prior experience reached 50% accuracy. Nearly half (47%) of the synthetic images were mistakenly evaluated as conventional. Interestingly, in a blinded quality assessment, a board-certified radiologist did not significantly differentiate between conventional and synthetic images in the context of the mean quality of synthetic and conventional images. Furthermore, to validate the usability of the generated synthetic images from prostate cancer MRIs, we subjected these to anomaly detection along with the original images. Importantly, the success rate of anomaly detection for quality control-approved synthetic data in phase one corresponded to that of the conventional images. In sum, this study shows promise that high-quality synthetic images from MRIs can be generated using GANs. Such an AI model may contribute significantly to various clinical applications which involve supervised machine-learning approaches. Full article

(This article belongs to the Section Personalized Therapy in Clinical Medicine)

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12 pages, 1871 KB

Open AccessEditor’s ChoiceArticle

Total Cholesterol Variability and the Risk of Osteoporotic Fractures: A Nationwide Population-Based Cohort Study

by Dongyeop Kim, Jee Hyun Kim and Tae-Jin Song

J. Pers. Med. 2023, 13(3), 509; https://doi.org/10.3390/jpm13030509 - 11 Mar 2023

Cited by 13 | Viewed by 2200

Abstract

Several risk factors for osteoporotic fractures have been identified but reports of the association of lipid parameters with the occurrence of osteoporotic fractures have been limited. We aimed to examine whether serum total cholesterol (TC) variability is associated with osteoporotic fractures. The study [...] Read more.

Several risk factors for osteoporotic fractures have been identified but reports of the association of lipid parameters with the occurrence of osteoporotic fractures have been limited. We aimed to examine whether serum total cholesterol (TC) variability is associated with osteoporotic fractures. The study included 3,00,326 subjects who had undergone three or more health examinations between 2003 and 2008. The primary endpoint was the incidence of osteoporotic fractures, including vertebral, hip, distal radius, and humerus fractures. TC variability was evaluated based on the following three parameters: coefficient of variation (CV), standard deviation (SD), and variability independent of the mean (VIM). A total of 29,044 osteoporotic fracture events (9.67%) were identified during a median of 11.6 years of follow-up. The risk of osteoporotic fractures in the highest quartile was significantly higher compared with the lowest quartile according to the three indices of TC variability with adjusted hazard ratios (HR) and 95% confidence intervals (CI) as follows: CV (HR 1.11, 95% CI [1.08–1.15]), SD (HR 1.07, 95% CI [1.04–1.11]) and VIM (HR 1.07, 95% CI [1.04–1.11]). The Kaplan–Meier curves showed a significantly positive relationship between the higher quartile of TC variability and overall osteoporotic fractures. The association remained significant in subgroup analyses of vertebral and hip fractures, regardless of the indices of TC variability. Our study showed that visit-to-visit TC variability was found to be associated with osteoporotic fracture risk. Maintaining TC levels stable may help attenuate the osteoporotic fracture risk in the future. Full article

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18 pages, 1310 KB

Open AccessFeature PaperEditor’s ChoiceReview

Can Opioid-Free Anaesthesia Be Personalised? A Narrative Review

by Jenna Goff, Morgan Hina, Nayaab Malik, Hannah McLardy, Finley Reilly, Matthew Robertson, Louis Ruddy, Faith Willox and Patrice Forget

J. Pers. Med. 2023, 13(3), 500; https://doi.org/10.3390/jpm13030500 - 10 Mar 2023

Cited by 19 | Viewed by 8536

Abstract

Background: A significant amount of evidence suggests that Opioid-Free Anaesthesia (OFA) may provide better outcomes for patients undergoing surgery, sparing patients who are particularly vulnerable to adverse side effects of opioids. However, to what extent personalizing OFA is feasible and beneficial has not [...] Read more.

Background: A significant amount of evidence suggests that Opioid-Free Anaesthesia (OFA) may provide better outcomes for patients undergoing surgery, sparing patients who are particularly vulnerable to adverse side effects of opioids. However, to what extent personalizing OFA is feasible and beneficial has not been adequately described. Methods: We conducted a narrative literature review aiming to provide a comprehensive understanding of nociception and pain and its context within the field of OFA. Physiological (including monitoring), pharmacological, procedural (type of surgery), genetical and phenotypical (including patients’ conditions) were considered. Results: We did not find any monitoring robustly associated with improved outcomes. However, we found evidence supporting particular OFA indications, such as bariatric and cancer surgery. We found that vulnerable patients may benefit more from OFA, with an interesting field of research in patients suffering from vascular disease. We found a variety of techniques and medications making it impossible to consider OFA as a single technique. Our findings suggest that a vast field of research remains unexplored. In particular, a deeper understanding of nociception with an interest in its genetic and acquired contributors would be an excellent starting point paving the way for personalised OFA. Conclusion: Recent developments in OFA may present a more holistic approach, challenging the use of opioids. Understanding better nociception, given the variety of OFA techniques, may help to maximize their potential in different contexts and potential indications. Full article

(This article belongs to the Special Issue New Paradigms in Anesthesia and Intensive Care)

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13 pages, 318 KB

Open AccessEditor’s ChoiceArticle

Identification of Transporter Polymorphisms Influencing Metformin Pharmacokinetics in Healthy Volunteers

by Miriam Saiz-Rodríguez, Dolores Ochoa, Pablo Zubiaur, Marcos Navares-Gómez, Manuel Román, Paola Camargo-Mamani, Sergio Luquero-Bueno, Gonzalo Villapalos-García, Raquel Alcaraz, Gina Mejía-Abril, Estefanía Santos-Mazo and Francisco Abad-Santos

J. Pers. Med. 2023, 13(3), 489; https://doi.org/10.3390/jpm13030489 - 8 Mar 2023

Cited by 14 | Viewed by 4219

Abstract

For patients with type 2 diabetes, metformin is the most often recommended drug. However, there are substantial individual differences in the pharmacological response to metformin. To investigate the effect of transporter polymorphisms on metformin pharmacokinetics in an environment free of confounding variables, we [...] Read more.

For patients with type 2 diabetes, metformin is the most often recommended drug. However, there are substantial individual differences in the pharmacological response to metformin. To investigate the effect of transporter polymorphisms on metformin pharmacokinetics in an environment free of confounding variables, we conducted our study on healthy participants. This is the first investigation to consider demographic characteristics alongside all transporters involved in metformin distribution. Pharmacokinetic parameters of metformin were found to be affected by age, sex, ethnicity, and several polymorphisms. Age and SLC22A4 and SLC47A2 polymorphisms affected the area under the concentration-time curve (AUC). However, after adjusting for dose-to-weight ratio (dW), sex, age, and ethnicity, along with SLC22A3 and SLC22A4, influenced AUC. The maximum concentration was affected by age and SLC22A1, but after adjusting for dW, it was affected by sex, age, ethnicity, ABCG2, and SLC22A4. The time to reach the maximum concentration was influenced by sex, like half-life, which was also affected by SLC22A3. The volume of distribution and clearance was affected by sex, age, ethnicity and SLC22A3. Alternatively, the pharmacokinetics of metformin was unaffected by polymorphisms in ABCB1, SLC2A2, SLC22A2, or SLC47A1. Therefore, our study demonstrates that a multifactorial approach to all patient characteristics is necessary for better individualization. Full article

(This article belongs to the Special Issue Precision Medicine Genomics: Pharmacogenomics)

18 pages, 7933 KB

Open AccessEditor’s ChoiceReview

Predicting the Onset of Diabetes with Machine Learning Methods

by Chun-Yang Chou, Ding-Yang Hsu and Chun-Hung Chou

J. Pers. Med. 2023, 13(3), 406; https://doi.org/10.3390/jpm13030406 - 24 Feb 2023

Cited by 113 | Viewed by 11937

Abstract

The number of people suffering from diabetes in Taiwan has continued to rise in recent years. According to the statistics of the International Diabetes Federation, about 537 million people worldwide (10.5% of the global population) suffer from diabetes, and it is estimated that [...] Read more.

The number of people suffering from diabetes in Taiwan has continued to rise in recent years. According to the statistics of the International Diabetes Federation, about 537 million people worldwide (10.5% of the global population) suffer from diabetes, and it is estimated that 643 million people will develop the condition (11.3% of the total population) by 2030. If this trend continues, the number will jump to 783 million (12.2%) by 2045. At present, the number of people with diabetes in Taiwan has reached 2.18 million, with an average of one in ten people suffering from the disease. In addition, according to the Bureau of National Health Insurance in Taiwan, the prevalence rate of diabetes among adults in Taiwan has reached 5% and is increasing each year. Diabetes can cause acute and chronic complications that can be fatal. Meanwhile, chronic complications can result in a variety of disabilities or organ decline. If holistic treatments and preventions are not provided to diabetic patients, it will lead to the consumption of more medical resources and a rapid decline in the quality of life of society as a whole. In this study, based on the outpatient examination data of a Taipei Municipal medical center, 15,000 women aged between 20 and 80 were selected as the subjects. These women were patients who had gone to the medical center during 2018–2020 and 2021–2022 with or without the diagnosis of diabetes. This study investigated eight different characteristics of the subjects, including the number of pregnancies, plasma glucose level, diastolic blood pressure, sebum thickness, insulin level, body mass index, diabetes pedigree function, and age. After sorting out the complete data of the patients, this study used Microsoft Machine Learning Studio to train the models of various kinds of neural networks, and the prediction results were used to compare the predictive ability of the various parameters for diabetes. Finally, this study found that after comparing the models using two-class logistic regression as well as the two-class neural network, two-class decision jungle, or two-class boosted decision tree for prediction, the best model was the two-class boosted decision tree, as its area under the curve could reach a score of 0.991, which was better than other models. Full article

(This article belongs to the Special Issue Applications of Machine Learning and Deep Learning in Precision Medicine)

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18 pages, 472 KB

Open AccessFeature PaperEditor’s ChoiceReview

Pharmacogenetics in the Treatment of Huntington’s Disease: Review and Future Perspectives

by Xandra García-González, Esther Cubo, Lucía Simón-Vicente, Natividad Mariscal, Raquel Alcaraz, Laura Aguado, Jéssica Rivadeneyra-Posadas, Antonio Sanz-Solas and Miriam Saiz-Rodríguez

J. Pers. Med. 2023, 13(3), 385; https://doi.org/10.3390/jpm13030385 - 22 Feb 2023

Cited by 17 | Viewed by 8883

Abstract

Huntington’s disease (HD) is an autosomal dominant progressive brain disorder, caused by a pathological expansion of a CAG repeat that encodes the huntingtin gene. This genetic neurodegenerative rare disease is characterized by cognitive, motor, and neuropsychiatric manifestations. The aim of the treatment is [...] Read more.

Huntington’s disease (HD) is an autosomal dominant progressive brain disorder, caused by a pathological expansion of a CAG repeat that encodes the huntingtin gene. This genetic neurodegenerative rare disease is characterized by cognitive, motor, and neuropsychiatric manifestations. The aim of the treatment is symptomatic and addresses the hyperkinetic disorders (chorea, dystonia, myoclonus, tics, etc.) and the behavioural and cognitive disturbances (depression, anxiety, psychosis, etc.) associated with the disease. HD is still a complex condition in need of innovative and efficient treatment. The long-term goal of pharmacogenetic studies is to use genotype data to predict the effective treatment response to a specific drug and, in turn, prevent potential undesirable effects of its administration. Chorea, depression, and psychotic symptoms have a substantial impact on HD patients’ quality of life and could be better controlled with the help of pharmacogenetic knowledge. We aimed to carry out a review of the available publications and evidence related to the pharmacogenetics of HD, with the objective of compiling all information that may be useful in optimizing drug administration. The impact of pharmacogenetic information on the response to antidepressants and antipsychotics is well documented in psychiatric patients, but this approach has not been investigated in HD patients. Future research should address several issues to ensure that pharmacogenetic clinical use is appropriately supported, feasible, and applicable. Full article

(This article belongs to the Special Issue Precision Medicine Genomics: Pharmacogenomics)

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13 pages, 1731 KB

Open AccessEditor’s ChoiceArticle

Multi-Modal Stacking Ensemble for the Diagnosis of Cardiovascular Diseases

by Taeyoung Yoon and Daesung Kang

J. Pers. Med. 2023, 13(2), 373; https://doi.org/10.3390/jpm13020373 - 20 Feb 2023

Cited by 54 | Viewed by 5281

Abstract

Background: Cardiovascular diseases (CVDs) are a leading cause of death worldwide. Deep learning methods have been widely used in the field of medical image analysis and have shown promising results in the diagnosis of CVDs. Methods: Experiments were performed on 12-lead electrocardiogram (ECG) [...] Read more.

Background: Cardiovascular diseases (CVDs) are a leading cause of death worldwide. Deep learning methods have been widely used in the field of medical image analysis and have shown promising results in the diagnosis of CVDs. Methods: Experiments were performed on 12-lead electrocardiogram (ECG) databases collected by Chapman University and Shaoxing People’s Hospital. The ECG signal of each lead was converted into a scalogram image and an ECG grayscale image and used to fine-tune the pretrained ResNet-50 model of each lead. The ResNet-50 model was used as a base learner for the stacking ensemble method. Logistic regression, support vector machine, random forest, and XGBoost were used as a meta learner by combining the predictions of the base learner. The study introduced a method called multi-modal stacking ensemble, which involves training a meta learner through a stacking ensemble that combines predictions from two modalities: scalogram images and ECG grayscale images. Results: The multi-modal stacking ensemble with a combination of ResNet-50 and logistic regression achieved an AUC of 0.995, an accuracy of 93.97%, a sensitivity of 0.940, a precision of 0.937, and an F1-score of 0.936, which are higher than those of LSTM, BiLSTM, individual base learners, simple averaging ensemble, and single-modal stacking ensemble methods. Conclusion: The proposed multi-modal stacking ensemble approach showed effectiveness for diagnosing CVDs. Full article

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

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27 pages, 419 KB

Open AccessEditor’s ChoiceReview

Biomarkers as Prognostic Predictors and Therapeutic Guide in Critically Ill Patients: Clinical Evidence

by Rosa Méndez Hernández and Fernando Ramasco Rueda

J. Pers. Med. 2023, 13(2), 333; https://doi.org/10.3390/jpm13020333 - 15 Feb 2023

Cited by 58 | Viewed by 10030

Abstract

A biomarker is a molecule that can be measured in a biological sample in an objective, systematic, and precise way, whose levels indicate whether a process is normal or pathological. Knowing the most important biomarkers and their characteristics is the key to precision [...] Read more.

A biomarker is a molecule that can be measured in a biological sample in an objective, systematic, and precise way, whose levels indicate whether a process is normal or pathological. Knowing the most important biomarkers and their characteristics is the key to precision medicine in intensive and perioperative care. Biomarkers can be used to diagnose, in assessment of disease severity, to stratify risk, to predict and guide clinical decisions, and to guide treatments and response to them. In this review, we will analyze what characteristics a biomarker should have and how to ensure its usefulness, and we will review the biomarkers that in our opinion can make their knowledge more useful to the reader in their clinical practice, with a future perspective. These biomarkers, in our opinion, are lactate, C-Reactive Protein, Troponins T and I, Brain Natriuretic Peptides, Procalcitonin, MR-ProAdrenomedullin and BioAdrenomedullin, Neutrophil/lymphocyte ratio and lymphopenia, Proenkephalin, NefroCheck, Neutrophil gelatinase-associated lipocalin (NGAL), Interleukin 6, Urokinase-type soluble plasminogen activator receptor (suPAR), Presepsin, Pancreatic Stone Protein (PSP), and Dipeptidyl peptidase 3 (DPP3). Finally, we propose an approach to the perioperative evaluation of high-risk patients and critically ill patients in the Intensive Care Unit (ICU) based on biomarkers. Full article

(This article belongs to the Special Issue New Paradigms in Anesthesia and Intensive Care)

40 pages, 1012 KB

Open AccessEditor’s ChoiceReview

Systemic Cytokines in Retinopathy of Prematurity

by Po-Yi Wu, Yuan-Kai Fu, Rey-In Lien, Ming-Chou Chiang, Chien-Chung Lee, Hung-Chi Chen, Yi-Jen Hsueh, Kuan-Jen Chen, Nan-Kai Wang, Laura Liu, Yen-Po Chen, Yih-Shiou Hwang, Chi-Chun Lai and Wei-Chi Wu

J. Pers. Med. 2023, 13(2), 291; https://doi.org/10.3390/jpm13020291 - 5 Feb 2023

Cited by 31 | Viewed by 5938

Abstract

Retinopathy of prematurity (ROP), a vasoproliferative vitreoretinal disorder, is the leading cause of childhood blindness worldwide. Although angiogenic pathways have been the main focus, cytokine-mediated inflammation is also involved in ROP etiology. Herein, we illustrate the characteristics and actions of all cytokines involved [...] Read more.

Retinopathy of prematurity (ROP), a vasoproliferative vitreoretinal disorder, is the leading cause of childhood blindness worldwide. Although angiogenic pathways have been the main focus, cytokine-mediated inflammation is also involved in ROP etiology. Herein, we illustrate the characteristics and actions of all cytokines involved in ROP pathogenesis. The two-phase (vaso-obliteration followed by vasoproliferation) theory outlines the evaluation of cytokines in a time-dependent manner. Levels of cytokines may even differ between the blood and the vitreous. Data from animal models of oxygen-induced retinopathy are also valuable. Although conventional cryotherapy and laser photocoagulation are well established and anti-vascular endothelial growth factor agents are available, less destructive novel therapeutics that can precisely target the signaling pathways are required. Linking the cytokines involved in ROP to other maternal and neonatal diseases and conditions provides insights into the management of ROP. Suppressing disordered retinal angiogenesis via the modulation of hypoxia-inducible factor, supplementation of insulin-like growth factor (IGF)-1/IGF-binding protein 3 complex, erythropoietin, and its derivatives, polyunsaturated fatty acids, and inhibition of secretogranin III have attracted the attention of researchers. Recently, gut microbiota modulation, non-coding RNAs, and gene therapies have shown promise in regulating ROP. These emerging therapeutics can be used to treat preterm infants with ROP. Full article

(This article belongs to the Special Issue Clinical and Translational Research in Ophthalmology)

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13 pages, 482 KB

Open AccessEditor’s ChoiceArticle

How Clinicians Conceptualize “Actionability” in Genomic Screening

by Kellie Owens, Pamela Sankar and Dina M. Asfaha

J. Pers. Med. 2023, 13(2), 290; https://doi.org/10.3390/jpm13020290 - 4 Feb 2023

Cited by 8 | Viewed by 2855

Abstract

Over the last decade, the concept of actionability has become a primary framework for assessing whether genetic data is useful and appropriate to return to patients. Despite the popularity of this concept, there is little consensus about what should count as “actionable” information. [...] Read more.

Over the last decade, the concept of actionability has become a primary framework for assessing whether genetic data is useful and appropriate to return to patients. Despite the popularity of this concept, there is little consensus about what should count as “actionable” information. This is particularly true in population genomic screening, where there is considerable disagreement about what counts as good evidence and which clinical actions are appropriate for which patients. The pathway from scientific evidence to clinical action is not straightforward—it is as much social and political as it is scientific. This research explores the social dynamics shaping the integration of “actionable” genomic data into primary care settings. Based on semi-structured interviews with 35 genetics experts and primary care providers, we find that clinicians vary in how they define and operationalize “actionable” information. There are two main sources of disagreement. First, clinicians differ on the levels and types of evidence required for a result to be actionable, such as when we can be confident that genomic data provides accurate information. Second, there are disagreements about the clinical actions that must be available so that patients can benefit from that information. By highlighting the underlying values and assumptions embedded in discussions of actionability for genomic screening, we provide an empirical basis for building more nuanced policies regarding the actionability of genomic data in terms of population screening in primary care settings. Full article

(This article belongs to the Special Issue Ethics in Expanding Precision Medicine to Population Health)

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23 pages, 843 KB

Open AccessEditor’s ChoiceReview

Lung Dysfunction and Chronic Kidney Disease: A Complex Network of Multiple Interactions

by Guido Gembillo, Sebastiano Calimeri, Valeria Tranchida, Salvatore Silipigni, Davide Vella, Domenico Ferrara, Claudia Spinella, Domenico Santoro and Luca Visconti

J. Pers. Med. 2023, 13(2), 286; https://doi.org/10.3390/jpm13020286 - 3 Feb 2023

Cited by 33 | Viewed by 21189

Abstract

Chronic kidney disease (CKD) is a progressive disease that affects > 10% of the total population worldwide or >800 million people. CKD poses a particularly heavy burden in low- and middle-income countries, which are least able to cope with its consequences. It has [...] Read more.

Chronic kidney disease (CKD) is a progressive disease that affects > 10% of the total population worldwide or >800 million people. CKD poses a particularly heavy burden in low- and middle-income countries, which are least able to cope with its consequences. It has become one of the leading causes of death worldwide and is one of the few non-communicable diseases where the number of related deaths has increased over the last two decades. The high number of people affected, and the significant negative impact of CKD should be a reason to increase efforts to improve prevention and treatment. The interaction of lung and kidney leads to highly complex and difficult clinical scenarios. CKD significantly affects the physiology of the lung by altering fluid homeostasis, acid-base balance and vascular tone. In the lung, haemodynamic disturbances lead to the development of alterations in ventilatory control, pulmonary congestion, capillary stress failure and pulmonary vascular disease. In the kidney, haemodynamic disturbances lead to sodium and water retention and the deterioration of renal function. In this article, we would like to draw attention to the importance of harmonising the definitions of clinical events in pneumology and renal medicine. We would also like to highlight the need for pulmonary function tests in routine clinical practise for the management of patients with CKD, in order to find new concepts for pathophysiological based disease-specific management strategies. Full article

(This article belongs to the Special Issue Personalized Medicine in Kidney Disease)

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11 pages, 15508 KB

Open AccessEditor’s ChoiceArticle

Parapharyngeal Space Tumors: Our Experience

by Jacopo Galli, Rolando Rolesi, Roberto Gallus, Annalisa Seccia, Alessandro Pedicelli, Francesco Bussu and Emanuele Scarano

J. Pers. Med. 2023, 13(2), 283; https://doi.org/10.3390/jpm13020283 - 2 Feb 2023

Cited by 7 | Viewed by 6145

Abstract

Para-pharyngeal space (PPS) tumors include an heterogeneous group of neoplasms, accounting for approximatively 0.5–1.5% of all head and neck tumors. Management of these neoplasms requires a careful diagnostic workout and an appropriate surgical approach to obtain good outcomes associated with minimal aesthetic drawbacks. [...] Read more.

Para-pharyngeal space (PPS) tumors include an heterogeneous group of neoplasms, accounting for approximatively 0.5–1.5% of all head and neck tumors. Management of these neoplasms requires a careful diagnostic workout and an appropriate surgical approach to obtain good outcomes associated with minimal aesthetic drawbacks. In this study we investigated clinical onset, histologic features, surgical treatment outcomes, peri operative complications and follow up of 98 patients treated for PPS tumors in our Centre between 2002 and 2021. Furthermore, we reviewed our preliminary experience of preoperative embolization of hyper vascular PPS tumors trough SQUID12, an ethylene vinyl alcohol copolymers (EVOH) which exhibits many advantages over other embolic agents, due to its better devascularization rate and lower risk of systemic complications. Our data support the hypothesis that transoral surgery scenario should be significantly revised, as it could represent a valid treatment for tumors located in lower and prestyloyd portion of PPS. Moreover, SQUID12, a novel embolization agent, may be a very promising choice for PPS hyper vascularized tumors, ensuring higher devascularization rate, safer procedures and lower risk of systemic dispersion compared to traditional Contour treatment. Full article

(This article belongs to the Special Issue Personalized Medicine in Otorhinolaryngology)

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17 pages, 1736 KB

Open AccessEditor’s ChoiceReview

Homologous Recombination Deficiency in Ovarian Cancer: from the Biological Rationale to Current Diagnostic Approaches

by Alessandro Mangogna, Giada Munari, Francesco Pepe, Edoardo Maffii, Pierluigi Giampaolino, Giuseppe Ricci, Matteo Fassan, Umberto Malapelle and Stefania Biffi

J. Pers. Med. 2023, 13(2), 284; https://doi.org/10.3390/jpm13020284 - 2 Feb 2023

Cited by 34 | Viewed by 9847

Abstract

The inability to efficiently repair DNA double-strand breaks using the homologous recombination repair pathway is defined as homologous recombination deficiency (HRD). This molecular phenotype represents a positive predictive biomarker for the clinical use of poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors and platinum-based chemotherapy [...] Read more.

The inability to efficiently repair DNA double-strand breaks using the homologous recombination repair pathway is defined as homologous recombination deficiency (HRD). This molecular phenotype represents a positive predictive biomarker for the clinical use of poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors and platinum-based chemotherapy in ovarian cancers. However, HRD is a complex genomic signature, and different methods of analysis have been developed to introduce HRD testing in the clinical setting. This review describes the technical aspects and challenges related to HRD testing in ovarian cancer and outlines the potential pitfalls and challenges that can be encountered in HRD diagnostics. Full article

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

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15 pages, 18093 KB

Open AccessEditor’s ChoiceArticle

PD-L1, CD4+, and CD8+ Tumor-Infiltrating Lymphocytes (TILs) Expression Profiles in Melanoma Tumor Microenvironment Cells

by Bogdan Marian Caraban, Elena Matei, Georgeta Camelia Cozaru, Mariana Aşchie, Mariana Deacu, Manuela Enciu, Gabriela Izabela Bălţătescu, Anca Chisoi, Nicolae Dobrin, Lucian Petcu, Emma Gheorghe, Laurențiu-Tony Hangan, Mihai Cătălin Roșu, Cristian Ionuț Orasanu and Antonela-Anca Nicolau

J. Pers. Med. 2023, 13(2), 221; https://doi.org/10.3390/jpm13020221 - 27 Jan 2023

Cited by 16 | Viewed by 3948

Abstract

(1) Background: Because melanoma is an aggressive tumor with an unfavorable prognosis, we aimed to characterize the PD-L1 expression in melanomas in association with T cell infiltrates because PD-1/PD-L1 blockade represents the target in treating melanoma strategy. (2) Methods: The immunohistochemical manual quantitative [...] Read more.

(1) Background: Because melanoma is an aggressive tumor with an unfavorable prognosis, we aimed to characterize the PD-L1 expression in melanomas in association with T cell infiltrates because PD-1/PD-L1 blockade represents the target in treating melanoma strategy. (2) Methods: The immunohistochemical manual quantitative methods of PD-L1, CD4, and CD8 TILs were performed in melanoma tumor microenvironment cells. (3) Results: Most of the PD-L1 positive, expressing tumors, have a moderate score of CD4+ TILs and CD8+TILs (5−50% of tumor area) in tumoral melanoma environment cells. The PD-L1 expression in TILs was correlated with different degrees of lymphocytic infiltration described by the Clark system (X² = 8.383, p = 0.020). PD-L1 expression was observed often in melanoma cases, with more than 2−4 mm of Breslow tumor thickness being the associated parameters (X² = 9.933, p = 0.014). (4) Conclusions: PD-L1 expression represents a predictive biomarker with very good accuracy for discriminating the presence or absence of malign tumoral melanoma cells. PD-L1 expression was an independent predictor of good prognosis in patients with melanomas. Full article

(This article belongs to the Special Issue Skin Cancers: Biomarkers and Potential Therapeutic Targets)

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