Journal of Personalized Medicine

15 pages, 1357 KiB

Open AccessEditor’s ChoiceArticle

Emergency Department Time Targets for Interhospital Transfer of Patients with Acute Ischemic Stroke

by Daian Popa, Aida Iancu, Alina Petrica, Florina Buleu, Carmen Gabriela Williams, Dumitru Sutoi, Cosmin Trebuian, Anca Tudor and Ovidiu Alexandru Mederle

J. Pers. Med. 2024, 14(1), 13; https://doi.org/10.3390/jpm14010013 - 21 Dec 2023

Cited by 6 | Viewed by 1425

Abstract

Background and objectives: Although the intravenous tissue plasminogen activator (rt-PA) has been shown to be effective in the treatment of acute ischemic stroke (AIS), only a small proportion of stroke patients receive this drug. The low administration rate is mainly due to [...] Read more.

Background and objectives: Although the intravenous tissue plasminogen activator (rt-PA) has been shown to be effective in the treatment of acute ischemic stroke (AIS), only a small proportion of stroke patients receive this drug. The low administration rate is mainly due to the delayed presentation of patients to the emergency department (ED) or the lack of a stroke team/unit in most of the hospitals. Thus, the aim of this study is to analyze ED time targets and the rate of rt-PA intravenous administration after the initial admission of patients with AIS in an ED from a traditional healthcare center (without a neurologist or stroke team/unit). Methods: To analyze which factors influence the administration of rt-PA, we split the general sample (n = 202) into two groups: group No rt-PA (n = 137) and group rt-PA (n = 65). This is based on the performing or no intravenous thrombolysis. Results: Analyzing ED time targets for all samples, we found that the median onset-to-ED door time was 180 min (IQR, 120–217.5 min), door-to-physician time was 4 min (IQR, 3–7 min), door-to-CT time was 52 min (IQR, 48–55 min), and door-in-door-out time was 61 min (IQR, 59–65 min). ED time targets such as door-to-physician time (p = 0.245), door-to-CT time (p = 0.219), door-in-door-out time (p = 0.24), NIHSS at admission to the Neurology department (p = 0.405), or NIHSS after 24 h (p = 0.9) did not have a statistically significant effect on the administration or no rt-PA treatment in patients included in our study. Only the highest door-to-CT time was statistically significantly correlated with the death outcome. Conclusion: In our study, the iv rt-PA administration rate was 32.18%. A statistically significant correlation between the highest door-to-CT time and death outcome was found. Full article

(This article belongs to the Special Issue Emergency Medicine: Clinical Advances and Challenges in Diagnosis and Treatment)

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54 pages, 7310 KiB

Open AccessEditor’s ChoiceReview

Survey of Transfer Learning Approaches in the Machine Learning of Digital Health Sensing Data

by Lina Chato and Emma Regentova

J. Pers. Med. 2023, 13(12), 1703; https://doi.org/10.3390/jpm13121703 - 12 Dec 2023

Cited by 7 | Viewed by 2834

Abstract

Machine learning and digital health sensing data have led to numerous research achievements aimed at improving digital health technology. However, using machine learning in digital health poses challenges related to data availability, such as incomplete, unstructured, and fragmented data, as well as issues [...] Read more.

Machine learning and digital health sensing data have led to numerous research achievements aimed at improving digital health technology. However, using machine learning in digital health poses challenges related to data availability, such as incomplete, unstructured, and fragmented data, as well as issues related to data privacy, security, and data format standardization. Furthermore, there is a risk of bias and discrimination in machine learning models. Thus, developing an accurate prediction model from scratch can be an expensive and complicated task that often requires extensive experiments and complex computations. Transfer learning methods have emerged as a feasible solution to address these issues by transferring knowledge from a previously trained task to develop high-performance prediction models for a new task. This survey paper provides a comprehensive study of the effectiveness of transfer learning for digital health applications to enhance the accuracy and efficiency of diagnoses and prognoses, as well as to improve healthcare services. The first part of this survey paper presents and discusses the most common digital health sensing technologies as valuable data resources for machine learning applications, including transfer learning. The second part discusses the meaning of transfer learning, clarifying the categories and types of knowledge transfer. It also explains transfer learning methods and strategies, and their role in addressing the challenges in developing accurate machine learning models, specifically on digital health sensing data. These methods include feature extraction, fine-tuning, domain adaptation, multitask learning, federated learning, and few-/single-/zero-shot learning. This survey paper highlights the key features of each transfer learning method and strategy, and discusses the limitations and challenges of using transfer learning for digital health applications. Overall, this paper is a comprehensive survey of transfer learning methods on digital health sensing data which aims to inspire researchers to gain knowledge of transfer learning approaches and their applications in digital health, enhance the current transfer learning approaches in digital health, develop new transfer learning strategies to overcome the current limitations, and apply them to a variety of digital health technologies. Full article

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

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22 pages, 1827 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Combination of Biological Therapy in Severe Asthma: Where We Are?

by Lorenzo Carriera, Marta Fantò, Alessia Martini, Alice D’Abramo, Genesio Puzio, Marco Umberto Scaramozzino and Angelo Coppola

J. Pers. Med. 2023, 13(11), 1594; https://doi.org/10.3390/jpm13111594 - 10 Nov 2023

Cited by 7 | Viewed by 2697

Abstract

Biological drugs have revolutionized the management of severe asthma. However, a variable number of patients remain uncontrolled or only partially controlled even after the appropriate administration of a biologic agent. The combination of two biologics may target different inflammatory pathways, and it has [...] Read more.

Biological drugs have revolutionized the management of severe asthma. However, a variable number of patients remain uncontrolled or only partially controlled even after the appropriate administration of a biologic agent. The combination of two biologics may target different inflammatory pathways, and it has been used in patients suffering from uncontrolled severe asthma with evidence of both allergic and eosinophilic phenotypes or severe asthma and type2 comorbidities. Combination therapy has also been used to handle anti-IL4/13R induced hypereosinophilia. There is insufficient data on combining biologics for the treatment of severe uncontrolled asthma and type 2 comorbidities, also because of the high cost, and currently no guideline recommends dual biologic therapy. A systematic search was performed using the Medline and Scopus databases. Published data on concurrent administration of two biological drugs in severe, uncontrolled asthma patients has been reported in 28 real-world studies and 1 clinical trial. Data extraction was followed by a descriptive and narrative synthesis of the findings. Future studies should be conducted to further assess the safety, efficacy, and cost-effectiveness of this therapeutic strategy. Full article

(This article belongs to the Special Issue Personalized Medicine in Asthma: Current Approach and Future Perspectives)

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29 pages, 708 KiB

Open AccessEditor’s ChoiceReview

miRNA-Based Technologies in Cancer Therapy

by Maria Pagoni, Claudia Cava, Diamantis C. Sideris, Margaritis Avgeris, Vassilios Zoumpourlis, Ioannis Michalopoulos and Nikolaos Drakoulis

J. Pers. Med. 2023, 13(11), 1586; https://doi.org/10.3390/jpm13111586 - 9 Nov 2023

Cited by 8 | Viewed by 3913

Abstract

The discovery of therapeutic miRNAs is one of the most exciting challenges for pharmaceutical companies. Since the first miRNA was discovered in 1993, our knowledge of miRNA biology has grown considerably. Many studies have demonstrated that miRNA expression is dysregulated in many diseases, [...] Read more.

The discovery of therapeutic miRNAs is one of the most exciting challenges for pharmaceutical companies. Since the first miRNA was discovered in 1993, our knowledge of miRNA biology has grown considerably. Many studies have demonstrated that miRNA expression is dysregulated in many diseases, making them appealing tools for novel therapeutic approaches. This review aims to discuss miRNA biogenesis and function, as well as highlight strategies for delivering miRNA agents, presenting viral, non-viral, and exosomic delivery as therapeutic approaches for different cancer types. We also consider the therapeutic role of microRNA-mediated drug repurposing in cancer therapy. Full article

(This article belongs to the Section Personalized Therapy and Drug Delivery)

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15 pages, 3347 KiB

Open AccessEditor’s ChoiceReview

Digital Twins in Healthcare: Methodological Challenges and Opportunities

by Charles Meijer, Hae-Won Uh and Said el Bouhaddani

J. Pers. Med. 2023, 13(10), 1522; https://doi.org/10.3390/jpm13101522 - 23 Oct 2023

Cited by 11 | Viewed by 4093

Abstract

One of the most promising advancements in healthcare is the application of digital twin technology, offering valuable applications in monitoring, diagnosis, and development of treatment strategies tailored to individual patients. Furthermore, digital twins could also be helpful in finding novel treatment targets and [...] Read more.

One of the most promising advancements in healthcare is the application of digital twin technology, offering valuable applications in monitoring, diagnosis, and development of treatment strategies tailored to individual patients. Furthermore, digital twins could also be helpful in finding novel treatment targets and predicting the effects of drugs and other chemical substances in development. In this review article, we consider digital twins as virtual counterparts of real human patients. The primary aim of this narrative review is to give an in-depth look into the various data sources and methodologies that contribute to the construction of digital twins across several healthcare domains. Each data source, including blood glucose levels, heart MRI and CT scans, cardiac electrophysiology, written reports, and multi-omics data, comes with different challenges regarding standardization, integration, and interpretation. We showcase how various datasets and methods are used to overcome these obstacles and generate a digital twin. While digital twin technology has seen significant progress, there are still hurdles in the way to achieving a fully comprehensive patient digital twin. Developments in non-invasive and high-throughput data collection, as well as advancements in modeling and computational power will be crucial to improve digital twin systems. We discuss a few critical developments in light of the current state of digital twin technology. Despite challenges, digital twin research holds great promise for personalized patient care and has the potential to shape the future of healthcare innovation. Full article

(This article belongs to the Special Issue Transforming Precision Medicine: The Intersection of Digital Health and AI)

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15 pages, 3274 KiB

Open AccessEditor’s ChoiceArticle

Challenging ChatGPT 3.5 in Senology—An Assessment of Concordance with Breast Cancer Tumor Board Decision Making

by Sebastian Griewing, Niklas Gremke, Uwe Wagner, Michael Lingenfelder, Sebastian Kuhn and Jelena Boekhoff

J. Pers. Med. 2023, 13(10), 1502; https://doi.org/10.3390/jpm13101502 - 16 Oct 2023

Cited by 16 | Viewed by 2518

Abstract

With the recent diffusion of access to publicly available large language models (LLMs), common interest in generative artificial-intelligence-based applications for medical purposes has skyrocketed. The increased use of these models by tech-savvy patients for personal health issues calls for a scientific evaluation of [...] Read more.

With the recent diffusion of access to publicly available large language models (LLMs), common interest in generative artificial-intelligence-based applications for medical purposes has skyrocketed. The increased use of these models by tech-savvy patients for personal health issues calls for a scientific evaluation of whether LLMs provide a satisfactory level of accuracy for treatment decisions. This observational study compares the concordance of treatment recommendations from the popular LLM ChatGPT 3.5 with those of a multidisciplinary tumor board for breast cancer (MTB). The study design builds on previous findings by combining an extended input model with patient profiles reflecting patho- and immunomorphological diversity of primary breast cancer, including primary metastasis and precancerous tumor stages. Overall concordance between the LLM and MTB is reached for half of the patient profiles, including precancerous lesions. In the assessment of invasive breast cancer profiles, the concordance amounts to 58.8%. Nevertheless, as the LLM makes considerably fraudulent decisions at times, we do not identify the current development status of publicly available LLMs to be adequate as a support tool for tumor boards. Gynecological oncologists should familiarize themselves with the capabilities of LLMs in order to understand and utilize their potential while keeping in mind potential risks and limitations. Full article

(This article belongs to the Special Issue Transforming Precision Medicine: The Intersection of Digital Health and AI)

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19 pages, 9005 KiB

Open AccessEditor’s ChoiceArticle

Optimized Convolutional Fusion for Multimodal Neuroimaging in Alzheimer’s Disease Diagnosis: Enhancing Data Integration and Feature Extraction

by Modupe Odusami, Rytis Maskeliūnas and Robertas Damaševičius

J. Pers. Med. 2023, 13(10), 1496; https://doi.org/10.3390/jpm13101496 - 14 Oct 2023

Cited by 7 | Viewed by 2284

Abstract

Multimodal neuroimaging has gained traction in Alzheimer’s Disease (AD) diagnosis by integrating information from multiple imaging modalities to enhance classification accuracy. However, effectively handling heterogeneous data sources and overcoming the challenges posed by multiscale transform methods remains a significant hurdle. This article proposes [...] Read more.

Multimodal neuroimaging has gained traction in Alzheimer’s Disease (AD) diagnosis by integrating information from multiple imaging modalities to enhance classification accuracy. However, effectively handling heterogeneous data sources and overcoming the challenges posed by multiscale transform methods remains a significant hurdle. This article proposes a novel approach to address these challenges. To harness the power of diverse neuroimaging data, we employ a strategy that leverages optimized convolution techniques. These optimizations include varying kernel sizes and the incorporation of instance normalization, both of which play crucial roles in feature extraction from magnetic resonance imaging (MRI) and positron emission tomography (PET) images. Specifically, varying kernel sizes allow us to adapt the receptive field to different image characteristics, enhancing the model’s ability to capture relevant information. Furthermore, we employ transposed convolution, which increases spatial resolution of feature maps, and it is optimized with varying kernel sizes and instance normalization. This heightened resolution facilitates the alignment and integration of data from disparate MRI and PET data. The use of larger kernels and strides in transposed convolution expands the receptive field, enabling the model to capture essential cross-modal relationships. Instance normalization, applied to each modality during the fusion process, mitigates potential biases stemming from differences in intensity, contrast, or scale between modalities. This enhancement contributes to improved model performance by reducing complexity and ensuring robust fusion. The performance of the proposed fusion method is assessed on three distinct neuroimaging datasets, which include: Alzheimer’s Disease Neuroimaging Initiative (ADNI), consisting of 50 participants each at various stages of AD for both MRI and PET (Cognitive Normal, AD, and Early Mild Cognitive); Open Access Series of Imaging Studies (OASIS), consisting of 50 participants each at various stages of AD for both MRI and PET (Cognitive Normal, Mild Dementia, Very Mild Dementia); and whole-brain atlas neuroimaging (AANLIB) (consisting of 50 participants each at various stages of AD for both MRI and PET (Cognitive Normal, AD). To evaluate the quality of the fused images generated via our method, we employ a comprehensive set of evaluation metrics, including Structural Similarity Index Measurement (SSIM), which assesses the structural similarity between two images; Peak Signal-to-Noise Ratio (PSNR), which measures how closely the generated image resembles the ground truth; Entropy (E), which assesses the amount of information preserved or lost during fusion; the Feature Similarity Indexing Method (FSIM), which assesses the structural and feature similarities between two images; and Edge-Based Similarity (EBS), which measures the similarity of edges between the fused and ground truth images. The obtained fused image is further evaluated using a Mobile Vision Transformer. In the classification of AD vs. Cognitive Normal, the model achieved an accuracy of 99.00%, specificity of 99.00%, and sensitivity of 98.44% on the AANLIB dataset. Full article

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34 pages, 2445 KiB

Open AccessEditor’s ChoiceReview

Probiotics and Probiotic-like Agents against Chemotherapy-Induced Intestinal Mucositis: A Narrative Review

by Laura López-Gómez, Alexandra Alcorta and Raquel Abalo

J. Pers. Med. 2023, 13(10), 1487; https://doi.org/10.3390/jpm13101487 - 12 Oct 2023

Cited by 8 | Viewed by 3317

Abstract

Cancer chemotherapy has allowed many patients to survive, but not without risks derived from its adverse effects. Drugs, such as 5-fluorouracil, irinotecan, oxaliplatin, methotrexate, and others, as well as different drug combinations trigger intestinal mucositis that may cause or contribute to anorexia, pain, [...] Read more.

Cancer chemotherapy has allowed many patients to survive, but not without risks derived from its adverse effects. Drugs, such as 5-fluorouracil, irinotecan, oxaliplatin, methotrexate, and others, as well as different drug combinations trigger intestinal mucositis that may cause or contribute to anorexia, pain, diarrhea, weight loss, systemic infections, and even death. Dysbiosis is a hallmark of chemotherapy-induced intestinal mucositis and diarrhea, and, therefore, strategies aimed at modulating intestinal microbiota may be useful to counteract and prevent those dreadful effects. This narrative review offers an overview of the studies performed to test the efficacy of probiotics and probiotic-like agents against chemotherapy-induced intestinal mucositis and its consequences. Microbiota modulation through the oral administration of different probiotics (mainly strains of Lactobacillus and Bifidobacterium), probiotic mixtures, synbiotics, postbiotics, and paraprobiotics has been tested in different animal models and in some clinical trials. Regulation of dysbiosis, modulation of epithelial barrier permeability, anti-inflammatory effects, modulation of host immune response, reduction of oxidative stress, or prevention of apoptosis are the main mechanisms involved in their beneficial effects. However, the findings are limited by the great heterogeneity of the preclinical studies and the relative lack of studies in immunocompromised animals, as well as the scarce availability of results from clinical trials. Despite this, the results accumulated so far are promising. Hopefully, with the aid of these agents, intestinal mucositis will be less impactful to the cancer patient in the near future. Full article

(This article belongs to the Special Issue Application of Microbiome in Disease Diagnosis and Treatment)

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17 pages, 1947 KiB

Open AccessEditor’s ChoiceReview

The Role of Uric Acid in Human Health: Insights from the Uricase Gene

by Youssef M. Roman

J. Pers. Med. 2023, 13(9), 1409; https://doi.org/10.3390/jpm13091409 - 20 Sep 2023

Cited by 9 | Viewed by 7480

Abstract

Uric acid is the final product of purine metabolism and is converted to allantoin in most mammals via the uricase enzyme. The accumulation of loss of function mutations in the uricase gene rendered hominoids (apes and humans) to have higher urate concentrations compared [...] Read more.

Uric acid is the final product of purine metabolism and is converted to allantoin in most mammals via the uricase enzyme. The accumulation of loss of function mutations in the uricase gene rendered hominoids (apes and humans) to have higher urate concentrations compared to other mammals. The loss of human uricase activity may have allowed humans to survive environmental stressors, evolution bottlenecks, and life-threatening pathogens. While high urate levels may contribute to developing gout and cardiometabolic disorders such as hypertension and insulin resistance, low urate levels may increase the risk for neurodegenerative diseases. The double-edged sword effect of uric acid has resurrected a growing interest in urate’s antioxidant role and the uricase enzyme’s role in modulating the risk of obesity. Characterizing both the effect of uric acid levels and the uricase enzyme in different animal models may provide new insights into the potential therapeutic benefits of uric acid and novel uricase-based therapy. Full article

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32 pages, 1177 KiB

Open AccessEditor’s ChoiceReview

Personalized Medicine in Oral Oncology: Imaging Methods and Biological Markers to Support Diagnosis of Oral Squamous Cell Carcinoma (OSCC): A Narrative Literature Review

by Dardo Menditti, Mario Santagata, Gianmaria Imola, Samuel Staglianò, Rita Vitagliano, Ciro Emiliano Boschetti and Angelo Michele Inchingolo

J. Pers. Med. 2023, 13(9), 1397; https://doi.org/10.3390/jpm13091397 - 19 Sep 2023

Cited by 5 | Viewed by 2043

Abstract

For decades, oral squamous cell carcinoma (OSCC) has been one of the most prevalent and mortal cancers worldwide. The gold standard for OSCC diagnosis is still histopathology but this narrative multidisciplinary review has the aim to explore the literature about conventional OSCC prognostic [...] Read more.

For decades, oral squamous cell carcinoma (OSCC) has been one of the most prevalent and mortal cancers worldwide. The gold standard for OSCC diagnosis is still histopathology but this narrative multidisciplinary review has the aim to explore the literature about conventional OSCC prognostic indicators related to the pTNM stage at the diagnosis such as the depth of invasion and the lymphovascular invasion associated with distant metastasis as indicators of poor life expectancy. Despite its multifactorial nature and recognizable precursors, its diagnosis at the early stages is still challenging. We wanted to highlight the importance of the screening as a primary weapon that a stomatologist should consider, intercepting all at-risk conditions and lesions associated with OSCC and its early stages. This narrative review also overviews the most promising imaging techniques, such as CT, MRI, and US-echography, and their application related to clinical and surgical practice, but also the most-investigated prognostic and diagnostic tissue and salivary biomarkers helpful in OSCC diagnosis and prognostic assessment. Our work highlighted remarkable potential biomarkers that could have a leading role in the future. However, we are still far from defining an appropriate and concrete protocol to apply in clinical practice. The hope is that the present and future research will overcome these limitations to benefit patients, clinicians, and welfare. Full article

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

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28 pages, 445 KiB

Open AccessEditor’s ChoiceReview

Associations of BDNF/BDNF-AS SNPs with Depression, Schizophrenia, and Bipolar Disorder

by Anton Shkundin and Angelos Halaris

J. Pers. Med. 2023, 13(9), 1395; https://doi.org/10.3390/jpm13091395 - 18 Sep 2023

Cited by 10 | Viewed by 3085

Abstract

Brain-Derived Neurotrophic Factor (BDNF) is crucial for various aspects of neuronal development and function, including synaptic plasticity, neurotransmitter release, and supporting neuronal differentiation, growth, and survival. It is involved in the formation and preservation of dopaminergic, serotonergic, GABAergic, and cholinergic neurons, facilitating efficient [...] Read more.

Brain-Derived Neurotrophic Factor (BDNF) is crucial for various aspects of neuronal development and function, including synaptic plasticity, neurotransmitter release, and supporting neuronal differentiation, growth, and survival. It is involved in the formation and preservation of dopaminergic, serotonergic, GABAergic, and cholinergic neurons, facilitating efficient stimulus transmission within the synaptic system and contributing to learning, memory, and overall cognition. Furthermore, BDNF demonstrates involvement in neuroinflammation and showcases neuroprotective effects. In contrast, BDNF antisense RNA (BDNF-AS) is linked to the regulation and control of BDNF, facilitating its suppression and contributing to neurotoxicity, apoptosis, and decreased cell viability. This review article aims to comprehensively overview the significance of single nucleotide polymorphisms (SNPs) in BDNF/BDNF-AS genes within psychiatric conditions, with a specific focus on their associations with depression, schizophrenia, and bipolar disorder. The independent influence of each BDNF/BDNF-AS gene variation, as well as the interplay between SNPs and their linkage disequilibrium, environmental factors, including early-life experiences, and interactions with other genes, lead to alterations in brain architecture and function, shaping vulnerability to mental health disorders. The potential translational applications of BDNF/BDNF-AS polymorphism knowledge can revolutionize personalized medicine, predict disease susceptibility, treatment outcomes, and guide the selection of interventions tailored to individual patients. Full article

(This article belongs to the Section Disease Biomarker)

17 pages, 2073 KiB

Open AccessEditor’s ChoiceArticle

Cardiac Troponin I but Not N-Terminal Pro-B-Type Natriuretic Peptide Predicts Outcomes in Cardiogenic Shock

by Tobias Schupp, Jonas Rusnak, Jan Forner, Kathrin Weidner, Marinela Ruka, Sascha Egner-Walter, Jonas Dudda, Thomas Bertsch, Maximilian Kittel, Michael Behnes and Ibrahim Akin

J. Pers. Med. 2023, 13(9), 1348; https://doi.org/10.3390/jpm13091348 - 31 Aug 2023

Cited by 5 | Viewed by 1189

Abstract

This study investigates the prognostic value of cardiac troponin I (cTNI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in patients with cardiogenic shock (CS). Data regarding the prognostic value of cardiac biomarkers in CS is scarce, furthermore, most studies were restricted to CS [...] Read more.

This study investigates the prognostic value of cardiac troponin I (cTNI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in patients with cardiogenic shock (CS). Data regarding the prognostic value of cardiac biomarkers in CS is scarce, furthermore, most studies were restricted to CS patients with acute myocardial infarction (AMI). Therefore, consecutive patients with CS from 2019 to 2021 were included. Blood samples were retrieved from day of disease onset (day 1) and on days 2, 3 and 4 thereafter. The prognostic value of cTNI and NT-proBNP levels was tested for 30-day all-cause mortality. Statistical analyses included univariable t-tests, Spearman’s correlations, Kaplan–Meier analyses and multivariable Cox proportional regression analyses. A total of 217 CS patients were included with an overall rate of all-cause mortality of 56% at 30 days. CTNI was able to discriminate 30-day non-survivors (area under the curve (AUC) = 0.669; p = 0.001), whereas NT-proBNP (AUC = 0.585; p = 0.152) was not. The risk of 30-day all-cause mortality was higher in patients with cTNI levels above the median (70% vs. 43%; log rank p = 0.001; HR = 2.175; 95% CI 1.510–3.132; p = 0.001), which was observed both in patients with (71% vs. 49%; log rank p = 0.012) and without AMI-related CS (69% vs. 40%; log rank p = 0.005). The prognostic impact of cTNI was confirmed after multivariable adjustment (HR = 1.915; 95% CI 1.298–2.824; p = 0.001). In conclusion, cTNI—but not NT-proBNP—levels discriminated 30-day all-cause mortality in CS patients. Full article

(This article belongs to the Special Issue Percutaneous Management of Complex Coronary Artery Disease—Updates on Clinical Outcomes, Management Strategies and Novel Techniques)

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17 pages, 1399 KiB

Open AccessEditor’s ChoiceReview

Antibody–Drug Conjugates for the Treatment of Renal Cancer: A Scoping Review on Current Evidence and Clinical Perspectives

by Stefano Sganga, Silvia Riondino, Giovanni Maria Iannantuono, Roberto Rosenfeld, Mario Roselli and Francesco Torino

J. Pers. Med. 2023, 13(9), 1339; https://doi.org/10.3390/jpm13091339 - 30 Aug 2023

Cited by 4 | Viewed by 2745

Abstract

Antibody–drug conjugates (ADCs) are complex chemical structures composed of a monoclonal antibody, serving as a link to target cells, which is conjugated with a potent cytotoxic drug (i.e., payload) through a chemical linker. Inspired by Paul Ehrlich’s concept of the ideal anticancer drug [...] Read more.

Antibody–drug conjugates (ADCs) are complex chemical structures composed of a monoclonal antibody, serving as a link to target cells, which is conjugated with a potent cytotoxic drug (i.e., payload) through a chemical linker. Inspired by Paul Ehrlich’s concept of the ideal anticancer drug as a “magic bullet”, ADCs are also highly specific anticancer agents, as they have been demonstrated to recognize, bind, and neutralize cancer cells, limiting injuries to normal cells. ADCs are among the newest pharmacologic breakthroughs in treating solid and hematologic malignancies. Indeed, in recent years, various ADCs have been approved by the Food and Drug Administration and European Medicines Agency for the treatment of several cancers, resulting in a “practice-changing” approach. However, despite these successes, no ADC is approved for treating patients affected by renal cell carcinoma (RCC). In the present paper, we thoroughly reviewed the current literature and summarized preclinical studies and clinical trials that evaluated the activity and toxicity profile of ADCs in RCC patients. Moreover, we scrutinized the potential causes that, until now, hampered the therapeutical success of ADCs in those patients. Finally, we discussed novel strategies that would improve the development of ADCs and their efficacy in treating RCC patients. Full article

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

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16 pages, 2093 KiB

Open AccessEditor’s ChoiceArticle

Carpal Tunnel Syndrome Associated with Immune Checkpoint Inhibitors

by Alexander Yakobson, Keren Rouvinov, Aharon Y. Cohen, Iris Goldstein, Omar Abu Saleh, Adam Solomon, Yulia Dudnik and Walid Shalata

J. Pers. Med. 2023, 13(9), 1340; https://doi.org/10.3390/jpm13091340 - 30 Aug 2023

Cited by 4 | Viewed by 1843

Abstract

Immune checkpoint inhibitors (ICIs) have transformed the therapeutic approach to diverse malignancies, leading to substantial enhancements in patient prognosis. However, along with their benefits, ICIs also increase the incidence of immune-related adverse events (irAEs). In the present paper, we highlight four cases of [...] Read more.

Immune checkpoint inhibitors (ICIs) have transformed the therapeutic approach to diverse malignancies, leading to substantial enhancements in patient prognosis. However, along with their benefits, ICIs also increase the incidence of immune-related adverse events (irAEs). In the present paper, we highlight four cases of carpal tunnel syndrome (CTS) as an uncommon manifestation of toxicity induced by ICIs. Although diagnosed with different malignancies, the patients were undergoing ICI therapy when they developed CTS-consistent side effects accompanied by severe neuropathy. Prompt treatment with corticosteroids, intravenous immunoglobulins, or methotrexate resulted in complete symptomatic relief for all patients. This article therefore emphasizes the importance of recognizing and managing rare adverse events associated with ICI use to ensure optimal patient care. Full article

(This article belongs to the Section Molecular Targeted Therapy)

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18 pages, 2617 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Airway Management: The Current Role of Videolaryngoscopy

by Sophie A. Saul, Patrick A. Ward and Alistair F. McNarry

J. Pers. Med. 2023, 13(9), 1327; https://doi.org/10.3390/jpm13091327 - 29 Aug 2023

Cited by 13 | Viewed by 3659

Abstract

Airway management is usually an uncomplicated and safe intervention; however, when problems arise with the primary airway technique, the clinical situation can rapidly deteriorate, resulting in significant patient harm. Videolaryngoscopy has been shown to improve patient outcomes when compared with direct laryngoscopy, including [...] Read more.

Airway management is usually an uncomplicated and safe intervention; however, when problems arise with the primary airway technique, the clinical situation can rapidly deteriorate, resulting in significant patient harm. Videolaryngoscopy has been shown to improve patient outcomes when compared with direct laryngoscopy, including improved first-pass success at tracheal intubation, reduced difficult laryngeal views, reduced oxygen desaturation, reduced airway trauma, and improved recognition of oesophageal intubation. The shared view that videolaryngoscopy affords may also facilitate superior teaching, training, and multidisciplinary team performance. As such, its recommended role in airway management has evolved from occasional use as a rescue device (when direct laryngoscopy fails) to a first-intention technique that should be incorporated into routine clinical practice, and this is reflected in recently updated guidelines from a number of international airway societies. However, currently, overall videolaryngoscopy usage is not commensurate with its now widespread availability. A number of factors exist that may be preventing its full adoption, including perceived financial costs, inadequacy of education and training, challenges in achieving deliverable decontamination processes, concerns over sustainability, fears over “de-skilling” at direct laryngoscopy, and perceived limitations of videolaryngoscopes. This article reviews the most up-to-date evidence supporting videolaryngoscopy, explores its current scope of utilisation (including specialist techniques), the potential barriers preventing its full adoption, and areas for future advancement and research. Full article

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

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14 pages, 8235 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Nanoparticle-Based Treatment in Glioblastoma

by Diogo Roque, Nuno Cruz, Hugo Alexandre Ferreira, Catarina Pinto Reis, Nuno Matela, Manuel Herculano-Carvalho, Rita Cascão and Claudia C. Faria

J. Pers. Med. 2023, 13(9), 1328; https://doi.org/10.3390/jpm13091328 - 29 Aug 2023

Cited by 8 | Viewed by 3269

Abstract

Glioblastoma (GB) is a malignant glioma associated with a mean overall survival of 12 to 18 months, even with optimal treatment, due to its high relapse rate and treatment resistance. The standardized first-line treatment consists of surgery, which allows for diagnosis and cytoreduction, [...] Read more.

Glioblastoma (GB) is a malignant glioma associated with a mean overall survival of 12 to 18 months, even with optimal treatment, due to its high relapse rate and treatment resistance. The standardized first-line treatment consists of surgery, which allows for diagnosis and cytoreduction, followed by stereotactic fractionated radiotherapy and chemotherapy. Treatment failure can result from the poor passage of drugs through the blood–brain barrier (BBB). The development of novel and more effective therapeutic approaches is paramount to increasing the life expectancy of GB patients. Nanoparticle-based treatments include epitopes that are designed to interact with specialized transport systems, ultimately allowing the crossing of the BBB, increasing therapeutic efficacy, and reducing systemic toxicity and drug degradation. Polymeric nanoparticles have shown promising results in terms of precisely directing drugs to the brain with minimal systemic side effects. Various methods of drug delivery that pass through the BBB, such as the stereotactic injection of nanoparticles, are being actively tested in vitro and in vivo in animal models. A significant variety of pre-clinical studies with polymeric nanoparticles for the treatment of GB are being conducted, with only a few nanoparticle-based drug delivery systems to date having entered clinical trials. Pre-clinical studies are key to testing the safety and efficacy of these novel anticancer therapies and will hopefully facilitate the testing of the clinical validity of this promising treatment method. Here we review the recent literature concerning the most frequently reported types of nanoparticles for the treatment of GB. Full article

(This article belongs to the Special Issue Precision Medicine in Neurooncology and Neurosurgery for the 21st Century)

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20 pages, 1118 KiB

Open AccessEditor’s ChoiceReview

Metabolic Syndrome and Atrial Fibrillation: Different Entities or Combined Disorders

by George E. Zakynthinos, Vasiliki Tsolaki, Evangelos Oikonomou, Manolis Vavouranakis, Gerasimos Siasos and Epaminondas Zakynthinos

J. Pers. Med. 2023, 13(9), 1323; https://doi.org/10.3390/jpm13091323 - 28 Aug 2023

Cited by 6 | Viewed by 1567

Abstract

Obesity, hypertension, insulin resistance, and dyslipidemia are all clusters of an entity called “Metabolic Syndrome”. The global trends of this syndrome’s incidence/prevalence continue to increase reciprocally, converting it into a massive epidemic problem in the medical community. Observing the risk factors of atrial [...] Read more.

Obesity, hypertension, insulin resistance, and dyslipidemia are all clusters of an entity called “Metabolic Syndrome”. The global trends of this syndrome’s incidence/prevalence continue to increase reciprocally, converting it into a massive epidemic problem in the medical community. Observing the risk factors of atrial fibrillation, a medical condition that is also converted to a scourge, almost all parts of the metabolic syndrome are encountered. In addition, several studies demonstrated a robust correlation between metabolic syndrome and the occurrence of atrial fibrillation. For atrial fibrillation to develop, a combination of the appropriate substrate and a trigger point is necessary. The metabolic syndrome affects the left atrium in a multifactorial way, leading to atrial remodeling, thus providing both the substrate and provoking the trigger needed, which possibly plays a substantial role in the progression of atrial fibrillation. Due to the remodeling, treatment of atrial fibrillation may culminate in pernicious sequelae, such as repeated catheter ablation procedures. A holistic approach of the patient, with simultaneous treatment of both entities, is suggested in order to ensure better outcomes for the patients. Full article

(This article belongs to the Special Issue Metabolic Syndrome and Cardiovascular Disease)

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12 pages, 1239 KiB

Open AccessEditor’s ChoiceArticle

Prognostic Value of Serum Biomarkers in Patients with Idiopathic Pulmonary Fibrosis in Relation to Disease Progression

by Kalliopi Domvri, Ioannis Organtzis, Apostolos Apostolopoulos, Evangelia Fouka, Theodoros Kontakiotis and Despoina Papakosta

J. Pers. Med. 2023, 13(9), 1307; https://doi.org/10.3390/jpm13091307 - 26 Aug 2023

Cited by 5 | Viewed by 1392

Abstract

Background: The aim of this present study was to determine serum biomarker levels and their correlation with respiratory function and the clinical course of patients with idiopathic pulmonary fibrosis (IPF). Materials and Methods: This study included 72 IPF patients, according to the ATS/ERS [...] Read more.

Background: The aim of this present study was to determine serum biomarker levels and their correlation with respiratory function and the clinical course of patients with idiopathic pulmonary fibrosis (IPF). Materials and Methods: This study included 72 IPF patients, according to the ATS/ERS criteria, in whom antifibrotic treatment was initiated. Blood samples were taken, and serum biomarkers, such as KL-6, SP-D, CCL18, CXCL13, VEGF-A, IL-8, IGFBP-1, IGFBP-2, IGFBP-7 and ICAM-1 were measured using ELISA methodology. Pulmonary function tests (FVC, TLC, DLCO-% pred) were determined at baseline and after 12 and 24 months and analyzed in correlation with the biomarkers. Results: The majority of patients (mean age 72 ± 6 years) were men (83%). The FVC and DLCO values at the 12-month follow-up were found to be statistically decreased in deceased patients (p < 0.05). The SP-D (p < 0.001) and the IGFBP-1 (p = 0.021) levels were found to be increased at the 1-year follow-up in deceased patients, and similarly, the SP-D (p = 0.005) and ICAM-1 (p = 0.043) levels at the 2-year follow-up. A chi-square test revealed that 70% of the category IV GAP index was found with cut-off elevated levels of a biomarker combination (KL-6, SP-D, VEGF-A) from the ROC curve analysis (p < 0.05). Conclusion: This study provides evidence, for the first time in a Greek population, of the possibility of using a combination of KL-6, SP-D, and VEGF-A serum levels along with the GAP index. Full article

(This article belongs to the Special Issue Biomarkers in Diagnosis and Treatment of Pulmonary Disease)

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22 pages, 2576 KiB

Open AccessEditor’s ChoiceReview

Unlocking the Potential of Mesenchymal Stem Cells in Gynecology: Where Are We Now?

by Ivana Erceg Ivkošić, Rajko Fureš, Vesna Ćosić, Nika Mikelin, Luka Bulić, Domagoj Dobranić, Petar Brlek and Dragan Primorac

J. Pers. Med. 2023, 13(8), 1253; https://doi.org/10.3390/jpm13081253 - 13 Aug 2023

Cited by 4 | Viewed by 3193

Abstract

Stem cells, with their remarkable capacity for differentiation into diverse cell types, are vital for the development as well as maintenance of health and homeostasis. Two unique abilities set them apart from other cells: self-renewal and the capacity for differentiation. They play important [...] Read more.

Stem cells, with their remarkable capacity for differentiation into diverse cell types, are vital for the development as well as maintenance of health and homeostasis. Two unique abilities set them apart from other cells: self-renewal and the capacity for differentiation. They play important roles in embryogenesis, development, regeneration, and various other processes. Over the last decade, there has been increased interest in their potential use in the treatment of numerous diseases and disorders across multiple fields of medicine in acute, chronic, innate, and acquired diseases. Stem cells are key to maintaining the body’s homeostasis and regulating growth and tissue functions. There are several types of stem cells—embryonic, adult, and human-induced pluripotent cells. Currently, mesenchymal stem cells are of great interest due to their regenerative, immunomodulatory, analgesic, and antimicrobial (anti-inflammatory) effects. Recent studies have shown the potent regenerative effect of stem cell therapy in gynecologic diseases such as infertility, Asherman syndrome, lichen sclerosus, polycystic ovary syndrome, premature ovarian insufficiency, genitourinary syndrome of menopause, and rectovaginal fistulas. Moreover, the successful isolation of oogonial stem cells could lead to a revolution in the field of gynecology and the potential treatment of the conditions discussed. This review aims to provide a better understanding of the latest therapeutic options involving stem cells and raise awareness of this promising yet not widely known topic in gynecology and medicine in general. Full article

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

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15 pages, 787 KiB

Open AccessEditor’s ChoiceReview

Intelligent Digital Twins for Personalized Migraine Care

by Parisa Gazerani

J. Pers. Med. 2023, 13(8), 1255; https://doi.org/10.3390/jpm13081255 - 13 Aug 2023

Cited by 9 | Viewed by 2853

Abstract

Intelligent digital twins closely resemble their real-life counterparts. In health and medical care, they enable the real-time monitoring of patients, whereby large amounts of data can be collected to produce actionable information. These powerful tools are constructed with the aid of artificial intelligence, [...] Read more.

Intelligent digital twins closely resemble their real-life counterparts. In health and medical care, they enable the real-time monitoring of patients, whereby large amounts of data can be collected to produce actionable information. These powerful tools are constructed with the aid of artificial intelligence, machine learning, and deep learning; the Internet of Things; and cloud computing to collect a diverse range of digital data (e.g., from digital patient journals, wearable sensors, and digitized monitoring equipment or processes), which can provide information on the health conditions and therapeutic responses of their physical twins. Intelligent digital twins can enable data-driven clinical decision making and advance the realization of personalized care. Migraines are a highly prevalent and complex neurological disorder affecting people of all ages, genders, and geographical locations. It is ranked among the top disabling diseases, with substantial negative personal and societal impacts, but the current treatment strategies are suboptimal. Personalized care for migraines has been suggested to optimize their treatment. The implementation of intelligent digital twins for migraine care can theoretically be beneficial in supporting patient-centric care management. It is also expected that the implementation of intelligent digital twins will reduce costs in the long run and enhance treatment effectiveness. This study briefly reviews the concept of digital twins and the available literature on digital twins for health disorders such as neurological diseases. Based on these, the potential construction and utility of digital twins for migraines will then be presented. The potential and challenges when implementing intelligent digital twins for the future management of migraines are also discussed. Full article

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

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13 pages, 607 KiB

Open AccessEditor’s ChoiceReview

State of the Art in Robotic Surgery with Hugo RAS System: Feasibility, Safety and Clinical Applications

by Francesco Prata, Alberto Ragusa, Claudia Tempesta, Andrea Iannuzzi, Francesco Tedesco, Loris Cacciatore, Gianluigi Raso, Angelo Civitella, Piergiorgio Tuzzolo, Pasquale Callè, Matteo Pira, Matteo Pino, Marco Ricci, Marco Fantozzi, Salvatore M. Prata, Umberto Anceschi, Giuseppe Simone, Roberto M. Scarpa and Rocco Papalia

J. Pers. Med. 2023, 13(8), 1233; https://doi.org/10.3390/jpm13081233 - 6 Aug 2023

Cited by 18 | Viewed by 3520

Abstract

Since its introduction in the early 2000s, robotic surgery has represented a significative innovation within a minimally invasive surgery approach. A variety of robotic platforms have been made available throughout the years, and the outcomes related to those platforms have been described in [...] Read more.

Since its introduction in the early 2000s, robotic surgery has represented a significative innovation within a minimally invasive surgery approach. A variety of robotic platforms have been made available throughout the years, and the outcomes related to those platforms have been described in the literature for many types of surgeries. Medtronic’s Hugo^TM RAS system is one of the newest robotic generations launched, but because of its recent placing on the field, comprehensive clinical data are still lacking. The aim of the present state of the art is to address the current literature concerning the use of the Hugo^TM RAS robot in order to report its feasibility, safety and clinical applications in different surgical branches. Two reviewers independently conducted a search on the “PubMed” electronic database, using the keywords “Hugo” and “Hugo RAS”. After the initial screening of 35 results, a total of 15 articles concerning the Hugo RAS system were selected for the review, including both oncological and benign surgery. Patients’ demographic and baseline data were compared including, when available, docking system times, complications and oncological outcomes in the fields of urologic, gynecologic and general surgery. With reference to urological procedures, a total of 156 robot-assisted radical prostatectomies, 10 robot-assisted partial nephrectomies, and 5 robot-assisted adrenalectomies were performed, involving a total of 171 patients. The surgical branch in which the Hugo system found its major application was urology, which was followed by gynecology and general surgery. The Hugo RAS system by Medtronic represents an innovative and safe surgical platform, with excellent perspective for the future and different clinical applications in many surgical branches. More studies are needed to validate the safety and results from this new robotic platform. Full article

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13 pages, 617 KiB

Open AccessEditor’s ChoiceReview

Advancing Patient Care: How Artificial Intelligence Is Transforming Healthcare

by Diana Gina Poalelungi, Carmina Liana Musat, Ana Fulga, Marius Neagu, Anca Iulia Neagu, Alin Ionut Piraianu and Iuliu Fulga

J. Pers. Med. 2023, 13(8), 1214; https://doi.org/10.3390/jpm13081214 - 31 Jul 2023

Cited by 23 | Viewed by 8895

Abstract

Artificial Intelligence (AI) has emerged as a transformative technology with immense potential in the field of medicine. By leveraging machine learning and deep learning, AI can assist in diagnosis, treatment selection, and patient monitoring, enabling more accurate and efficient healthcare delivery. The widespread [...] Read more.

Artificial Intelligence (AI) has emerged as a transformative technology with immense potential in the field of medicine. By leveraging machine learning and deep learning, AI can assist in diagnosis, treatment selection, and patient monitoring, enabling more accurate and efficient healthcare delivery. The widespread implementation of AI in healthcare has the role to revolutionize patients’ outcomes and transform the way healthcare is practiced, leading to improved accessibility, affordability, and quality of care. This article explores the diverse applications and reviews the current state of AI adoption in healthcare. It concludes by emphasizing the need for collaboration between physicians and technology experts to harness the full potential of AI. Full article

(This article belongs to the Special Issue Patient-Centered Care for Chronic Diseases)

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16 pages, 1400 KiB

Open AccessEditor’s ChoiceReview

Immune Biomarkers in Triple-Negative Breast Cancer: Improving the Predictivity of Current Testing Methods

by Francesca Maria Porta, Elham Sajjadi, Konstantinos Venetis, Chiara Frascarelli, Giulia Cursano, Elena Guerini-Rocco, Nicola Fusco and Mariia Ivanova

J. Pers. Med. 2023, 13(7), 1176; https://doi.org/10.3390/jpm13071176 - 23 Jul 2023

Cited by 9 | Viewed by 3101

Abstract

Triple-negative breast cancer (TNBC) poses a significant challenge in terms of prognosis and disease recurrence. The limited treatment options and the development of resistance to chemotherapy make it particularly difficult to manage these patients. However, recent research has been shifting its focus towards [...] Read more.

Triple-negative breast cancer (TNBC) poses a significant challenge in terms of prognosis and disease recurrence. The limited treatment options and the development of resistance to chemotherapy make it particularly difficult to manage these patients. However, recent research has been shifting its focus towards biomarker-based approaches for TNBC, with a particular emphasis on the tumor immune landscape. Immune biomarkers in TNBC are now a subject of great interest due to the presence of tumor-infiltrating lymphocytes (TILs) in these tumors. This characteristic often coincides with the presence of PD-L1 expression on both neoplastic cells and immune cells within the tumor microenvironment. Furthermore, a subset of TNBC harbor mismatch repair deficient (dMMR) TNBC, which is frequently accompanied by microsatellite instability (MSI). All of these immune biomarkers hold actionable potential for guiding patient selection in immunotherapy. To fully capitalize on these opportunities, the identification of additional or complementary biomarkers and the implementation of highly customized testing strategies are of paramount importance in TNBC. In this regard, this article aims to provide an overview of the current state of the art in immune-related biomarkers for TNBC. Specifically, it focuses on the various testing methodologies available and sheds light on the immediate future perspectives for patient selection. By delving into the advancements made in understanding the immune landscape of TNBC, this study aims to contribute to the growing body of knowledge in the field. The ultimate goal is to pave the way for the development of more personalized testing strategies, ultimately improving outcomes for TNBC patients. Full article

(This article belongs to the Special Issue Cancer Biomarkers and Therapy)

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17 pages, 3434 KiB

Open AccessEditor’s ChoiceArticle

Mid-Regional Pro-Adrenomedullin and N-Terminal Pro-B-Type Natriuretic Peptide Measurement: A Multimarker Approach to Diagnosis and Prognosis in Acute Heart Failure

by Silvia Spoto, Josepmaria Argemi, Roberta Di Costanzo, Juan Josè Gavira Gomez, Nahikari Salterain Gonzales, Stefania Basili, Roberto Cangemi, Antonio Abbate, Luciana Locorriere, Francesco Masini, Giulia Testorio, Rodolfo Calarco, Giulia Battifoglia, Fabio Mangiacapra, Marta Fogolari, Sebastiano Costantino and Silvia Angeletti

J. Pers. Med. 2023, 13(7), 1155; https://doi.org/10.3390/jpm13071155 - 18 Jul 2023

Cited by 6 | Viewed by 1772

Abstract

Background: Acute heart failure (AHF) is a major cause of hospitalization and mortality worldwide. Early and accurate diagnosis, as well as effective risk stratification, are essential for optimizing clinical management and improving patient outcomes. In this context, biomarkers have gained increasing interest in [...] Read more.

Background: Acute heart failure (AHF) is a major cause of hospitalization and mortality worldwide. Early and accurate diagnosis, as well as effective risk stratification, are essential for optimizing clinical management and improving patient outcomes. In this context, biomarkers have gained increasing interest in recent years as they can provide important diagnostic and prognostic information in patients with AHF. Aim and Methods: The primary objective of the present study was to compare the levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-adrenomedullin (MR-proADM), and C-reactive protein (CRP) between patients diagnosed with acute heart failure (AHF) and those without AHF and sepsis. Furthermore, the study aimed to assess the diagnostic and prognostic value of the use of a multimarker approach in AHF patients. To achieve these objectives, a total of 145 patients with AHF and 127 patients without AHF and sepsis, serving as the control group, were consecutively enrolled in the study. Results: Levels of MR-proADM (median: 2.07; (25th–75th percentiles: 1.40–3.02) vs. 1.11 (0.83–1.71) nmol/L, p < 0.0001), and NT-proBNP (5319 (1691–11,874) vs. 271 (89–931.5) pg/mL, p < 0.0001) were significantly higher in patients with AHF compared to controls, whereas CRP levels did not show significant differences. The mortality rate in the AHF group during in-hospital stay was 12%, and the rate of new re-admission for AHF within 30 days after discharge was 10%. During in-hospital follow-up, Cox regression analyses showed that levels of NT-proBNP > 10,132 pg/mL (hazard ratio (HR) 2.97; 95% confidence interval (CI): 1.13–7.82; p = 0.0284) and levels of MR-proADM > 2.8 nmol/L (HR: 8.57; CI: 2.42–30.28; p = 0.0009) predicted mortality. The combined use of MR-proADM and NT-proBNP provided significant additive predictive value for mortality and new re-admission for AHF at 30 days after discharge. A logistic regression analysis showed that the presence of NT-proBNP pg/mL > 12,973 pg mL and/or MR-proADM > 4.2 nmol/L predicted hospital re-admission within 30 days (OR: 3.23; CI: 1.05–9.91; p = 0.041). Conclusion: The combined assay of MR-proADM and NT-proBNP could be helpful in accurately identifying AHF and in defining prognosis and re-admission for AHF. The complementary use of these biomarkers can provide a useful clinical evaluation of AHF while also orienting clinicians to the pathophysiology underlying heart damage and assisting them in tailoring therapy. Full article

(This article belongs to the Section Disease Biomarker)

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12 pages, 2360 KiB

Open AccessEditor’s ChoiceArticle

The Clinical Efficacy of Contouring Periarticular Plates on a 3D Printed Bone Model

by Seung-yeob Sakong, Jae-Woo Cho, Beom-Soo Kim, Sung-Jun Park, Eic-Ju Lim and Jong-Keon Oh

J. Pers. Med. 2023, 13(7), 1145; https://doi.org/10.3390/jpm13071145 - 17 Jul 2023

Cited by 5 | Viewed by 1352

Abstract

We report our experience of preoperative plate contouring for periarticular fractures using three-dimensional printing (3DP) technology and describe its benefits. We enrolled 34 patients, including 11 with humerus midshaft fractures, 12 with tibia plateau fractures, 2 with pilon fractures, and 9 with acetabulum [...] Read more.

We report our experience of preoperative plate contouring for periarticular fractures using three-dimensional printing (3DP) technology and describe its benefits. We enrolled 34 patients, including 11 with humerus midshaft fractures, 12 with tibia plateau fractures, 2 with pilon fractures, and 9 with acetabulum fractures. The entire process of plate contouring over the 3DP model was videotaped and retrospectively analyzed. The total time and number of trials for the intraoperative positioning of precontoured plates and any further intraoperative contouring events were prospectively recorded. The mismatch between the planned and postoperative plate positions was evaluated. The average plate contouring time was 9.2 min for humerus shaft, 13.8 min for tibia plateau fractures, 8.8 min for pilon fractures, and 11.6 min for acetabular fractures. Most precontoured plates (88%, 30/34) could sit on the planned position without mismatch. In addition, only one patient with humerus shaft fracture required additional intraoperative contouring. Preoperative patient specific periarticular plate contouring using a 3DP model is a simple and efficient method that may alleviate the surgical challenges involved in plate contouring and positioning. Full article

(This article belongs to the Special Issue Personalized Management in Orthopedics and Traumatology)

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14 pages, 2202 KiB

Open AccessEditor’s ChoiceArticle

Using Anatomy-Based Fitting to Reduce Frequency-to-Place Mismatch in Experienced Bilateral Cochlear Implant Users: A Promising Concept

by Anja Kurz, David Herrmann, Rudolf Hagen and Kristen Rak

J. Pers. Med. 2023, 13(7), 1109; https://doi.org/10.3390/jpm13071109 - 8 Jul 2023

Cited by 7 | Viewed by 2078

Abstract

Fitting cochlear implant (CI) users can be challenging. Anatomy-based fitting (ABF) maps may have the potential to lead to better objective and subjective outcomes than conventional clinically based fitting (CBF) methods. ABF maps were created via information derived from exact electrode contact positions, [...] Read more.

Fitting cochlear implant (CI) users can be challenging. Anatomy-based fitting (ABF) maps may have the potential to lead to better objective and subjective outcomes than conventional clinically based fitting (CBF) methods. ABF maps were created via information derived from exact electrode contact positions, which were determined via post-operative high-resolution flat panel volume computer tomography and clinical fitting software. The outcome measures were speech understanding in quiet and noise and self-perceived sound quality with the CBF map and with the ABF map. Participants were 10 experienced bilateral CI users. The ABF map provided better speech understanding in quiet and noisy environments compared to the CBF map. Additionally, two approaches of reducing the frequency-to-place mismatch revealed that participants are more likely to accept the ABF map if their electrode array is inserted deep enough to stimulate the apical region of their cochlea. This suggests an Angular Insertion Depth of the most apical contact of around 720°–620°. Participants had better speech understanding in quiet and noise with the ABF map. The maps’ self-perceived sound quality was similar. ABF mapping may be an effective tool for compensating the frequency-to-place mismatch in experienced bilateral CI users. Full article

(This article belongs to the Special Issue Personalized Medicine in Otolaryngology: Special Topic Otology)

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14 pages, 1786 KiB

Open AccessEditor’s ChoiceArticle

Pancreas Rejection in the Artificial Intelligence Era: New Tool for Signal Patients at Risk

by Emanuel Vigia, Luís Ramalhete, Rita Ribeiro, Inês Barros, Beatriz Chumbinho, Edite Filipe, Ana Pena, Luís Bicho, Ana Nobre, Sofia Carrelha, Mafalda Sobral, Jorge Lamelas, João Santos Coelho, Aníbal Ferreira and Hugo Pinto Marques

J. Pers. Med. 2023, 13(7), 1071; https://doi.org/10.3390/jpm13071071 - 29 Jun 2023

Cited by 4 | Viewed by 1531

Abstract

Introduction: Pancreas transplantation is currently the only treatment that can re-establish normal endocrine pancreatic function. Despite all efforts, pancreas allograft survival and rejection remain major clinical problems. The purpose of this study was to identify features that could signal patients at risk of [...] Read more.

Introduction: Pancreas transplantation is currently the only treatment that can re-establish normal endocrine pancreatic function. Despite all efforts, pancreas allograft survival and rejection remain major clinical problems. The purpose of this study was to identify features that could signal patients at risk of pancreas allograft rejection. Methods: We collected 74 features from 79 patients who underwent simultaneous pancreas–kidney transplantation (SPK) and used two widely-applicable classification methods, the Naive Bayesian Classifier and Support Vector Machine, to build predictive models. We used the area under the receiver operating characteristic curve and classification accuracy to evaluate the predictive performance via leave-one-out cross-validation. Results: Rejection events were identified in 13 SPK patients (17.8%). In feature selection approach, it was possible to identify 10 features, namely: previous treatment for diabetes mellitus with long-term Insulin (U/I/day), type of dialysis (peritoneal dialysis, hemodialysis, or pre-emptive), de novo DSA, vPRA_Pre-Transplant (%), donor blood glucose, pancreas donor risk index (pDRI), recipient height, dialysis time (days), warm ischemia (minutes), recipient of intensive care (days). The results showed that the Naive Bayes and Support Vector Machine classifiers prediction performed very well, with an AUROC and classification accuracy of 0.97 and 0.87, respectively, in the first model and 0.96 and 0.94 in the second model. Conclusion: Our results indicated that it is feasible to develop successful classifiers for the prediction of graft rejection. The Naive Bayesian generated nomogram can be used for rejection probability prediction, thus supporting clinical decision making. Full article

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

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14 pages, 478 KiB

Open AccessEditor’s ChoiceReview

Acute-On-Chronic Liver Failure: Current Interventional Treatment Options and Future Challenges

by Markus Kimmann and Jonel Trebicka

J. Pers. Med. 2023, 13(7), 1052; https://doi.org/10.3390/jpm13071052 - 26 Jun 2023

Cited by 5 | Viewed by 2330

Abstract

Acute-on-chronic liver failure (ACLF) is a frequent complication in patients with liver cirrhosis that has high short-term mortality. It is characterized by acute decompensation (AD) of liver cirrhosis, intra- and extrahepatic organ failure, and severe systemic inflammation (SI). In the recent past, several [...] Read more.

Acute-on-chronic liver failure (ACLF) is a frequent complication in patients with liver cirrhosis that has high short-term mortality. It is characterized by acute decompensation (AD) of liver cirrhosis, intra- and extrahepatic organ failure, and severe systemic inflammation (SI). In the recent past, several studies have investigated the management of this group of patients. Identification and treatment of precipitants of decompensation and ACLF play an important role, and management of the respective intra- and extrahepatic organ failures is essential. However, no specific treatment for ACLF has been established to date, and the only curative treatment option currently available for these patients is liver transplantation (LT). It has been shown that ACLF patients are at severe risk of waitlist mortality, and post-LT survival rates are high, making ACLF patients suitable candidates for LT. However, only a limited number of patients are eligible for LT due to related contraindications such as uncontrolled infections. In this case, bridging strategies (e.g., extracorporeal organ support systems) are required. Further therapeutic approaches have recently been developed and evaluated. Thus, this review focuses on current management and potential future treatment options. Full article

(This article belongs to the Special Issue Novel Challenges and Therapeutic Options for Liver Diseases)

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16 pages, 3510 KiB

Open AccessEditor’s ChoiceArticle

ATR-FTIR Spectroscopy with Chemometrics for Analysis of Saliva Samples Obtained in a Lung-Cancer-Screening Programme: Application of Swabs as a Paradigm for High Throughput in a Clinical Setting

by Francis L. Martin, Andrew W. Dickinson, Tarek Saba, Thomas Bongers, Maneesh N. Singh and Danielle Bury

J. Pers. Med. 2023, 13(7), 1039; https://doi.org/10.3390/jpm13071039 - 25 Jun 2023

Cited by 8 | Viewed by 1849

Abstract

There is an increasing need for inexpensive and rapid screening tests in point-of-care clinical oncology settings. Herein, we develop a swab “dip” test in saliva obtained from consenting patients participating in a lung-cancer-screening programme being undertaken in North West England. In a pilot [...] Read more.

There is an increasing need for inexpensive and rapid screening tests in point-of-care clinical oncology settings. Herein, we develop a swab “dip” test in saliva obtained from consenting patients participating in a lung-cancer-screening programme being undertaken in North West England. In a pilot study, a total of 211 saliva samples (n = 170 benign, 41 designated cancer-positive) were randomly taken during the course of this prospective lung-cancer-screening programme. The samples (sterile Copan blue rayon swabs dipped in saliva) were analysed using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy. An exploratory analysis using principal component analysis (PCA,) with or without linear discriminant analysis (LDA), was then undertaken. Three pairwise comparisons were undertaken including: (1) benign vs. cancer following swab analysis; (2) benign vs. cancer following swab analysis with the subtraction of dry swab spectra; and (3) benign vs. cancer following swab analysis with the subtraction of wet swab spectra. Consistent and remarkably similar patterns of clustering for the benign control vs. cancer categories, irrespective of whether the swab plus saliva sample was analysed or whether there was a subtraction of wet or dry swab spectra, was observed. In each case, MANOVA demonstrated that this segregation of categories is highly significant. A k-NN (using three nearest neighbours) machine-learning algorithm also showed that the specificity (90%) and sensitivity (75%) are consistent for each pairwise comparison. In detailed analyses, the swab as a substrate did not alter the level of spectral discrimination between benign control vs. cancer saliva samples. These results demonstrate a novel swab “dip” test using saliva as a biofluid that is highly applicable to be rolled out into a larger lung-cancer-screening programme. Full article

(This article belongs to the Special Issue Clinical Applications of Biospectroscopy and Imaging)

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13 pages, 1115 KiB

Open AccessEditor’s ChoiceArticle

Precision Medicine Is Changing the Roles of Healthcare Professionals, Scientists, and Research Staff: Learnings from a Childhood Cancer Precision Medicine Trial

by Rebecca Daly, Kate Hetherington, Emily Hazell, Bethany R. Wadling, Vanessa Tyrrell, Katherine M. Tucker, Glenn M. Marshall, David S. Ziegler, Loretta M. S. Lau, Toby N. Trahair, Tracey A. O’Brien, Kiri Collins, Andrew J. Gifford, Michelle Haber, Mark Pinese, David Malkin, Mark J. Cowley, Jonathan Karpelowsky, Donna Drew, Chris Jacobs and Claire E. Wakefield Show full author list Hide full author list

J. Pers. Med. 2023, 13(7), 1033; https://doi.org/10.3390/jpm13071033 - 23 Jun 2023

Cited by 6 | Viewed by 3360

Abstract

Precision medicine programs aim to utilize novel technologies to identify personalized treatments for children with cancer. Delivering these programs requires interdisciplinary efforts, yet the many groups involved are understudied. This study explored the experiences of a broad range of professionals delivering Australia’s first [...] Read more.

Precision medicine programs aim to utilize novel technologies to identify personalized treatments for children with cancer. Delivering these programs requires interdisciplinary efforts, yet the many groups involved are understudied. This study explored the experiences of a broad range of professionals delivering Australia’s first precision medicine trial for children with poor-prognosis cancer: the PRecISion Medicine for Children with Cancer (PRISM) national clinical trial of the Zero Childhood Cancer Program. We conducted semi-structured interviews with 85 PRISM professionals from eight professional groups, including oncologists, surgeons, clinical research associates, scientists, genetic professionals, pathologists, animal care technicians, and nurses. We analyzed interviews thematically. Professionals shared that precision medicine can add complexity to their role and result in less certain outcomes for families. Although many participants described experiencing a greater emotional impact from their work, most expressed very positive views about the impact of precision medicine on their profession and its future potential. Most reported navigating precision medicine without formal training. Each group described unique challenges involved in adapting to precision medicine in their profession. Addressing training gaps and meeting the specific needs of many professional groups involved in precision medicine will be essential to ensure the successful implementation of standard care. Full article

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21 pages, 350 KiB

Open AccessEditor’s ChoiceReview

A Critical Review of the Prognostic and Predictive Implications of KRAS and STK11 Mutations and Co-Mutations in Metastatic Non-Small Lung Cancer

by Peter Manolakos and Linda D. Ward

J. Pers. Med. 2023, 13(6), 1010; https://doi.org/10.3390/jpm13061010 - 18 Jun 2023

Cited by 9 | Viewed by 2774

Abstract

The Kirsten rat sarcoma viral oncogene homolog (KRAS) and serine/threonine kinase 11 (STK11) co-mutations are associated with the diverse phenotypic and heterogeneous oncogenic subtypes in non-small cell lung cancer (NSCLC). Due to extensive mixed evidence, there needs to be [...] Read more.

The Kirsten rat sarcoma viral oncogene homolog (KRAS) and serine/threonine kinase 11 (STK11) co-mutations are associated with the diverse phenotypic and heterogeneous oncogenic subtypes in non-small cell lung cancer (NSCLC). Due to extensive mixed evidence, there needs to be a review of the recent KRAS and STK11 mutation literature to better understand the potential clinical applications of these genomic biomarkers in the current treatment landscape. This critical review highlights the clinical studies that have elucidated the potential prognostic and predictive implications of KRAS mutations, STK11 mutations, or KRAS/STK11 co-mutations when treating metastatic NSCLC across various types of treatments (e.g., immune checkpoint inhibitors [ICIs]). Overall, KRAS mutations are associated with poor prognoses and have been determined to be a valid but weak prognostic biomarker among patients diagnosed with NSCLC. KRAS mutations in NSCLC have shown mixed results as a predictive clinical biomarker for immune checkpoint inhibitor treatment. Overall, the studies in this review demonstrate that STK11 mutations are prognostic and show mixed results as predictive biomarkers for ICI therapy. However, KRAS/STK11 co-mutations may predict primary resistance to ICI. Prospective KRAS/STK11-biomarker-driven randomized trials are needed to assess the predictive effect of various treatments on the outcomes for patients with metastatic NSCLC, as the majority of the published KRAS analyses are retrospective and hypothesis-generating in nature. Full article

14 pages, 1800 KiB

Open AccessEditor’s ChoiceArticle

MGMT Promoter Methylation: Prognostication beyond Treatment Response

by Keyoumars Ashkan, Asfand Baig Mirza, Christos Soumpasis, Christoforos Syrris, Dimitrios Kalaitzoglou, Chaitanya Sharma, Zachariah Joseph James, Abbas Khizar Khoja, Razna Ahmed, Amisha Vastani, James Bartram, Kazumi Chia, Omar Al-Salihi, Angela Swampilai, Lucy Brazil, Ross Laxton, Zita Reisz, Istvan Bodi, Andrew King, Richard Gullan, Francesco Vergani, Ranjeev Bhangoo, Safa Al-Sarraj and Jose Pedro Lavrador Show full author list Hide full author list

J. Pers. Med. 2023, 13(6), 999; https://doi.org/10.3390/jpm13060999 - 14 Jun 2023

Cited by 5 | Viewed by 2197

Abstract

MGMT promoter methylation is related to the increased sensitivity of tumour tissue to chemotherapy with temozolomide (TMZ) and thus to improved patient survival. However, it is unclear how the extent of MGMT promoter methylation affects outcomes. In our study, a single-centre retrospective study, [...] Read more.

MGMT promoter methylation is related to the increased sensitivity of tumour tissue to chemotherapy with temozolomide (TMZ) and thus to improved patient survival. However, it is unclear how the extent of MGMT promoter methylation affects outcomes. In our study, a single-centre retrospective study, we explore the impact of MGMT promoter methylation in patients with glioblastoma who were operated upon with 5-ALA. Demographic, clinical and histology data, and survival rates were assessed. A total of 69 patients formed the study group (mean age 53.75 ± 15.51 years old). Positive 5-ALA fluorescence was noted in 79.41%. A higher percentage of MGMT promoter methylation was related to lower preoperative tumour volume (p = 0.003), a lower likelihood of 5-ALA positive fluorescence (p = 0.041) and a larger extent of resection EoR (p = 0.041). A higher MGMT promoter methylation rate was also related to improved progression-free survival (PFS) and overall survival (OS) (p = 0.008 and p = 0.006, respectively), even when adjusted for the extent of resection (p = 0.034 and p = 0.042, respectively). A higher number of adjuvant chemotherapy cycles was also related to longer PFS and OS (p = 0.049 and p = 0.030, respectively). Therefore, this study suggests MGMT promoter methylation should be considered as a continuous variable. It is a prognostic factor that goes beyond sensitivity to chemotherapy treatment, as a higher percentage of methylation is related not only to increased EoR and increased PFS and OS, but also to lower tumour volume at presentation and a lower likelihood of 5-ALA fluorescence intraoperatively. Full article

(This article belongs to the Special Issue Precision Medicine in Neurooncology and Neurosurgery for the 21st Century)

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23 pages, 915 KiB

Open AccessEditor’s ChoiceReview

The Pathophysiology, Identification and Management of Fracture Risk, Sublesional Osteoporosis and Fracture among Adults with Spinal Cord Injury

by Beverley Catharine Craven, Christopher M. Cirnigliaro, Laura D. Carbone, Philemon Tsang and Leslie R. Morse

J. Pers. Med. 2023, 13(6), 966; https://doi.org/10.3390/jpm13060966 - 8 Jun 2023

Cited by 10 | Viewed by 3376

Abstract

Background: The prevention of lower extremity fractures and fracture-related morbidity and mortality is a critical component of health services for adults living with chronic spinal cord injury (SCI). Methods: Established best practices and guideline recommendations are articulated in recent international consensus documents from [...] Read more.

Background: The prevention of lower extremity fractures and fracture-related morbidity and mortality is a critical component of health services for adults living with chronic spinal cord injury (SCI). Methods: Established best practices and guideline recommendations are articulated in recent international consensus documents from the International Society of Clinical Densitometry, the Paralyzed Veterans of America Consortium for Spinal Cord Medicine and the Orthopedic Trauma Association. Results: This review is a synthesis of the aforementioned consensus documents, which highlight the pathophysiology of lower extremity bone mineral density (BMD) decline after acute SCI. The role and actions treating clinicians should take to screen, diagnose and initiate the appropriate treatment of established low bone mass/osteoporosis of the hip, distal femur or proximal tibia regions associated with moderate or high fracture risk or diagnose and manage a lower extremity fracture among adults with chronic SCI are articulated. Guidance regarding the prescription of dietary calcium, vitamin D supplements, rehabilitation interventions (passive standing, functional electrical stimulation (FES) or neuromuscular electrical stimulation (NMES)) to modify bone mass and/or anti-resorptive drug therapy (Alendronate, Denosumab, or Zoledronic Acid) is provided. In the event of lower extremity fracture, the need for timely orthopedic consultation for fracture diagnosis and interprofessional care following definitive fracture management to prevent health complications (venous thromboembolism, pressure injury, and autonomic dysreflexia) and rehabilitation interventions to return the individual to his/her pre-fracture functional abilities is emphasized. Conclusions: Interprofessional care teams should use recent consensus publications to drive sustained practice change to mitigate fracture incidence and fracture-related morbidity and mortality among adults with chronic SCI. Full article

(This article belongs to the Special Issue Pathophysiology and Treatment of Secondary Conditions after Spinal Cord Injury)

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31 pages, 1401 KiB

Open AccessFeature PaperEditor’s ChoiceReview

The Spectrum of Extraglandular Manifestations in Primary Sjögren’s Syndrome

by Ancuta Mihai, Constantin Caruntu, Ciprian Jurcut, Florin Cristian Blajut, Mihnea Casian, Daniela Opris-Belinski, Ruxandra Ionescu and Ana Caruntu

J. Pers. Med. 2023, 13(6), 961; https://doi.org/10.3390/jpm13060961 - 7 Jun 2023

Cited by 5 | Viewed by 4214

Abstract

Extraglandular manifestations (EGMs) in primary Sjogren’s syndrome (pSS) represent the clinical expression of the systemic involvement in this disease. EGMs are characterized by a wide heterogeneity; virtually any organ or system can be affected, with various degrees of dysfunction. The existing gaps of [...] Read more.

Extraglandular manifestations (EGMs) in primary Sjogren’s syndrome (pSS) represent the clinical expression of the systemic involvement in this disease. EGMs are characterized by a wide heterogeneity; virtually any organ or system can be affected, with various degrees of dysfunction. The existing gaps of knowledge in this complex domain of extraglandular extension in pSS need to be overcome in order to increase the diagnostic accuracy of EGMs in pSS. The timely identification of EGMs, as early as from subclinical stages, can be facilitated using highly specific biomarkers, thus preventing decompensated disease and severe complications. To date, there is no general consensus on the diagnostic criteria for the wide range of extraglandular involvement in pSS, which associates important underdiagnosing of EGMs, subsequent undertreatment and progression to severe organ dysfunction in these patients. This review article presents the most recent basic and clinical science research conducted to investigate pathogenic mechanisms leading to EGMs in pSS patients. In addition, it presents the current diagnostic and treatment recommendations and the trends for future therapeutic strategies based on personalized treatment, as well as the latest research in the field of diagnostic and prognostic biomarkers for extraglandular involvement in pSS. Full article

(This article belongs to the Special Issue The Challenges and Therapeutic Prospects in Autoimmune Diseases)

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15 pages, 893 KiB

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 4 | Viewed by 2009

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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17 pages, 937 KiB

Open AccessEditor’s ChoiceReview

Shear Wave Dispersion in Chronic Liver Disease: From Physical Principles to Clinical Usefulness

by Matteo Garcovich, Mattia Paratore, Maria Elena Ainora, Laura Riccardi, Maurizio Pompili, Antonio Gasbarrini and Maria Assunta Zocco

J. Pers. Med. 2023, 13(6), 945; https://doi.org/10.3390/jpm13060945 - 2 Jun 2023

Cited by 7 | Viewed by 1780

Abstract

The development of new applications in ultrasound (US) imaging in recent years has strengthened the role of this imaging technique in the management of different pathologies, particularly in the setting of liver disease. Improved B-mode imaging (3D and 4D), contrast-enhanced US (CEUS) and [...] Read more.

The development of new applications in ultrasound (US) imaging in recent years has strengthened the role of this imaging technique in the management of different pathologies, particularly in the setting of liver disease. Improved B-mode imaging (3D and 4D), contrast-enhanced US (CEUS) and especially US-based elastography techniques have created the concept of multiparametric ultrasound (MP-US), a term borrowed from radiological sectional imaging. Among the new elastography techniques, shear wave dispersion is a newly developed imaging technology which enables the assessment of the shear waves’ dispersion slope. The analysis of the dispersion qualities of shear waves might be indirectly related to the tissue viscosity, thus providing biomechanical information concerning the pathologic state of the liver such as necroinflammation. Some of the most recent US devices have been embedded with software that evaluate the dispersion of shear waves/liver viscosity. In this review, the feasibility and the clinical applications of liver viscosity are reviewed based on the preliminary findings of both animal and human studies. Full article

(This article belongs to the Special Issue Towards Personalized Medicine for Chronic Liver Disease)

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13 pages, 1044 KiB

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 6 | Viewed by 1878

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 KiB

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 3 | Viewed by 2354

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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19 pages, 359 KiB

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 3 | Viewed by 3352

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)

12 pages, 299 KiB

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 12 | Viewed by 2873

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 KiB

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 6 | Viewed by 2574

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 KiB

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 7 | Viewed by 2139

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 KiB

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 8 | Viewed by 2840

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 Clinical Medicine, Cell, and Organism Physiology)

16 pages, 2362 KiB

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 8 | Viewed by 2154

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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12 pages, 298 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Is There an Advantage of Ultrathin-Strut Drug-Eluting Stents over Second- and Third-Generation Drug-Eluting Stents?

by Flavius-Alexandru Gherasie, Chioncel Valentin and Stefan-Sebastian Busnatu

J. Pers. Med. 2023, 13(5), 753; https://doi.org/10.3390/jpm13050753 - 28 Apr 2023

Cited by 6 | Viewed by 2268

Abstract

In patients undergoing percutaneous coronary intervention, the second-generation drug-eluting stents (DES) are considered the gold standard of care for revascularization. By reducing neointimal hyperplasia, drug-eluting coronary stents decrease the need for repeat revascularizations compared with conventional coronary stents without an antiproliferative drug coating. [...] Read more.

In patients undergoing percutaneous coronary intervention, the second-generation drug-eluting stents (DES) are considered the gold standard of care for revascularization. By reducing neointimal hyperplasia, drug-eluting coronary stents decrease the need for repeat revascularizations compared with conventional coronary stents without an antiproliferative drug coating. It is important to note that early-generation DESs were associated with an increased risk of very late stent thrombosis, most likely due to delayed endothelialization or a delayed hypersensitivity reaction to the polymer. Studies have shown a lower risk of very late stent thrombosis with developing second-generation DESs with biocompatible and biodegradable polymers or without polymers altogether. In addition, research has indicated that thinner struts are associated with a reduced risk of intrastent restenosis and angiographic and clinical results. A DES with ultrathin struts (strut thickness of 70 µm) is more flexible, facilitates better tracking, and is more crossable than a conventional second-generation DES. The question is whether ultrathin eluting drug stents suit all kinds of lesions. Several authors have reported that improved coverage with less thrombus protrusion reduced the risk of distal embolization in patients with ST-elevation myocardial infarction (STEMI). Others have described that an ultrathin stent might recoil due to low radial strength. This could lead to residual stenosis and repeated revascularization of the artery. In CTO patients, the ultrathin stent failed to prove non-inferiority regarding in-segment late lumen loss and showed statistically higher rates of restenosis. Ultrathin-strut DESs with biodegradable polymers have limitations when treating calcified (or ostial) lesions and CTOs. However, they also possess certain advantages regarding deliverability (tight stenosis, tortuous lesions, high angulation, etc.), ease of use in bifurcation lesions, better endothelialization and vascular healing, and reducing stent thrombosis risk. In light of this, ultrathin-strut stents present a promising alternative to existing DESs of the second and third generation. The aims of the study are to compare ultrathin eluting stents with second- and third-generation conventional stents regarding procedural performance and outcomes based on different lesion types and specific populations. Full article

(This article belongs to the Special Issue Contemporary Transcatheter Interventions)

20 pages, 890 KiB

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 11 | Viewed by 4865

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 KiB

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 13 | Viewed by 4180

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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15 pages, 987 KiB

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 9 | Viewed by 2017

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 Clinical Medicine, Cell, and Organism Physiology)

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12 pages, 296 KiB

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 6 | Viewed by 2440

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

20 pages, 1875 KiB

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 6 | Viewed by 1560

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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