Journal of Personalized Medicine

Review

12 pages, 3969 KiB

Open AccessEditor’s ChoiceReview

Gender Differences in Acute Aortic Dissection

by Eduardo Bossone, Andreina Carbone and Kim A. Eagle

J. Pers. Med. 2022, 12(7), 1148; https://doi.org/10.3390/jpm12071148 - 15 Jul 2022

Cited by 10 | Viewed by 2689

Cardiovascular disease (CVD) represents the most important cause of mortality and morbidity worldwide. There is heterogeneity in the epidemiology and management of CVD between male and female patients. In the specific case of acute aortic dissection (AAD), women, at the time of diagnosis, [...] Read more.

Cardiovascular disease (CVD) represents the most important cause of mortality and morbidity worldwide. There is heterogeneity in the epidemiology and management of CVD between male and female patients. In the specific case of acute aortic dissection (AAD), women, at the time of diagnosis, are older than men and complain less frequently of an abrupt onset of pain with delayed presentation to the emergency department. Furthermore, a history of hypertension and chronic obstructive pulmonary disease is more common among women. In type A AAD, women more often experience pleural effusion and coronary artery compromise, but experience less neurological and malperfusion symptoms. They undergo less frequent surgical treatment and have higher overall in-hospital mortality. Conversely, in type B AAD no significant differences were shown for in-hospital mortality between the two genders. However, it should be highlighted that further studies are needed in order to develop AAD gender specific preventive, diagnostic and therapeutic strategies. Full article

(This article belongs to the Special Issue Personalized Medicine Interdisciplinary Aspects and Sex Gender-Specific Differences)

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17 pages, 2350 KiB

Open AccessEditor’s ChoiceReview

Management of Patients with Severe Asthma and Chronic Rhinosinusitis with Nasal Polyps: A Multidisciplinary Shared Approach

by Veronica Seccia, Maria D’Amato, Giulia Scioscia, Diego Bagnasco, Fabiano Di Marco, Gianluca Fadda, Francesco Menzella, Ernesto Pasquini, Girolamo Pelaia, Eugenio Tremante, Eugenio De Corso and Matteo Bonini

J. Pers. Med. 2022, 12(7), 1096; https://doi.org/10.3390/jpm12071096 - 1 Jul 2022

Cited by 16 | Viewed by 4151

Abstract

Chronic rhinosinusitis (CRS) is one of the most frequent comorbidities associated with asthma and it contributes to an amplified global disease burden in asthmatics. CRS prevalence is much higher in asthmatic patients compared to the general population and it is more frequently related [...] Read more.

Chronic rhinosinusitis (CRS) is one of the most frequent comorbidities associated with asthma and it contributes to an amplified global disease burden in asthmatics. CRS prevalence is much higher in asthmatic patients compared to the general population and it is more frequently related to severe asthma, especially in presence of nasal polyps (chronic rhinosinusitis with nasal polyps, CRSwNP). Moreover, asthma exacerbation has a higher occurrence in CRSwNP. From a pathologic point of view, CRS and asthma share similar and connected mechanisms (e.g., type-2 inflammation). A multidisciplinary approach represents a crucial aspect for the optimal management of patients with concomitant asthma and CRSwNP and improvement of patient quality of life. An Italian panel of clinicians with different clinical expertise (pulmonologists, ear, nose and throat specialists, immunologists and allergy physicians) identified three different profiles of patients with coexisting asthma and nasal symptoms and discussed the specific tracks to guide a comprehensive approach to their diagnostic and therapeutic management. Currently available biological agents for the treatment of severe asthma act either on eosinophil-centered signaling network or type-2 inflammation, resulting to be effective also in CRSwNP and representing a valid option for patients with concomitant conditions. Full article

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

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18 pages, 1067 KiB

Open AccessEditor’s ChoiceReview

Eosinophilic Asthma, Phenotypes-Endotypes and Current Biomarkers of Choice

by Konstantinos Porpodis, Ioanna Tsiouprou, Apostolos Apostolopoulos, Polyxeni Ntontsi, Evangelia Fouka, Despoina Papakosta, Harissios Vliagoftis and Kalliopi Domvri

J. Pers. Med. 2022, 12(7), 1093; https://doi.org/10.3390/jpm12071093 - 30 Jun 2022

Cited by 15 | Viewed by 6901

Abstract

Asthma phenotyping and endotyping are constantly evolving. Currently, several biologic agents have been developed towards a personalized approach to asthma management. This review will focus on different eosinophilic phenotypes and Th2-associated endotypes with eosinophilic inflammation. Additionally, airway remodeling is analyzed as a key [...] Read more.

Asthma phenotyping and endotyping are constantly evolving. Currently, several biologic agents have been developed towards a personalized approach to asthma management. This review will focus on different eosinophilic phenotypes and Th2-associated endotypes with eosinophilic inflammation. Additionally, airway remodeling is analyzed as a key feature of asthmatic eosinophilic endotypes. In addition, evidence of biomarkers is examined with a predictive value to identify patients with severe, uncontrolled asthma who may benefit from new treatment options. Finally, there will be a discussion on the results from clinical trials regarding severe eosinophilic asthma and how the inhibition of the eosinophilic pathway by targeted treatments has led to the reduction of recurrent exacerbations. Full article

(This article belongs to the Special Issue Asthma: From Phenotypes to Personalized Medicine)

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16 pages, 5564 KiB

Open AccessEditor’s ChoiceReview

Atlas of PD-L1 for Pathologists: Indications, Scores, Diagnostic Platforms and Reporting Systems

by Stefano Marletta, Nicola Fusco, Enrico Munari, Claudio Luchini, Alessia Cimadamore, Matteo Brunelli, Giulia Querzoli, Maurizio Martini, Elena Vigliar, Romano Colombari, Ilaria Girolami, Fabio Pagni and Albino Eccher

J. Pers. Med. 2022, 12(7), 1073; https://doi.org/10.3390/jpm12071073 - 29 Jun 2022

Cited by 46 | Viewed by 6372

Abstract

Background. Innovative drugs targeting the PD1/PD-L1 axis have opened promising scenarios in modern cancer therapy. Plenty of assays and scoring systems have been developed for the evaluation of PD-L1 immunohistochemical expression, so far considered the most reliable therapeutic predictive marker. Methods. By gathering [...] Read more.

Background. Innovative drugs targeting the PD1/PD-L1 axis have opened promising scenarios in modern cancer therapy. Plenty of assays and scoring systems have been developed for the evaluation of PD-L1 immunohistochemical expression, so far considered the most reliable therapeutic predictive marker. Methods. By gathering the opinion of acknowledged experts in dedicated fields of pathology, we sought to update the currently available evidence on PD-L1 assessment in various types of tumors. Results. Robust data were progressively collected for several anatomic districts and leading international agencies to approve specific protocols: among these, TPS with 22C3, SP142 and SP263 clones in lung cancer; IC with SP142 antibody in breast, lung and urothelial tumors; and CPS with 22C3/SP263 assays in head and neck and urothelial carcinomas. On the other hand, for other malignancies, such as gastroenteric neoplasms, immunotherapy has been only recently introduced, often for particular histotypes, so specific guidelines are still lacking. Conclusions. PD-L1 immunohistochemical scoring is currently the basis for allowing many cancer patients to receive properly targeted therapies. While protocols supported by proven data are already available for many tumors, dedicated studies and clinical trials focusing on harmonization of the topic in other still only partially explored fields are surely yet advisable. Full article

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

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21 pages, 664 KiB

Open AccessEditor’s ChoiceReview

The Current State of Radiotherapy for Pediatric Brain Tumors: An Overview of Post-Radiotherapy Neurocognitive Decline and Outcomes

by Nicholas Major, Neal A. Patel, Josiah Bennett, Ena Novakovic, Dana Poloni, Mickey Abraham, Nolan J. Brown, Julian L. Gendreau, Ronald Sahyouni and Joshua Loya

J. Pers. Med. 2022, 12(7), 1050; https://doi.org/10.3390/jpm12071050 - 27 Jun 2022

Cited by 11 | Viewed by 2625

Abstract

Tumors of the central nervous system are the most common solid malignancies diagnosed in children. While common, they are also found to have some of the lowest survival rates of all malignancies. Treatment of childhood brain tumors often consists of operative gross total [...] Read more.

Tumors of the central nervous system are the most common solid malignancies diagnosed in children. While common, they are also found to have some of the lowest survival rates of all malignancies. Treatment of childhood brain tumors often consists of operative gross total resection with adjuvant chemotherapy or radiotherapy. The current body of literature is largely inconclusive regarding the overall benefit of adjuvant chemo- or radiotherapy. However, it is known that both are associated with conditions that lower the quality of life in children who undergo those treatments. Chemotherapy is often associated with nausea, emesis, significant fatigue, immunosuppression, and alopecia. While radiotherapy can be effective for achieving local control, it is associated with late effects such as endocrine dysfunction, secondary malignancy, and neurocognitive decline. Advancements in radiotherapy grant both an increase in lifetime survival and an increased lifetime for survivors to contend with these late effects. In this review, the authors examined all the published literature, analyzing the results of clinical trials, case series, and technical notes on patients undergoing radiotherapy for the treatment of tumors of the central nervous system with a focus on neurocognitive decline and survival outcomes. Full article

(This article belongs to the Special Issue Personalized Treatment Approaches for Paediatric Tumours of the Central Nervous System)

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12 pages, 284 KiB

Open AccessEditor’s ChoiceReview

Biologic Therapies in Pediatric Asthma

by Evanthia P. Perikleous, Paschalis Steiropoulos, Evangelia Nena and Emmanouil Paraskakis

J. Pers. Med. 2022, 12(6), 999; https://doi.org/10.3390/jpm12060999 - 18 Jun 2022

Cited by 14 | Viewed by 3122

Abstract

Undeniably, childhood asthma is a multifactorial and heterogeneous chronic condition widespread in children. Its management, especially of the severe form refractory to standard therapy remains challenging. Over the past decades, the development of biologic agents and their subsequent approval has provided an advanced [...] Read more.

Undeniably, childhood asthma is a multifactorial and heterogeneous chronic condition widespread in children. Its management, especially of the severe form refractory to standard therapy remains challenging. Over the past decades, the development of biologic agents and their subsequent approval has provided an advanced and very promising treatment alternative, eventually directing toward a successful precision medicine approach. The application of currently approved add-on treatments for severe asthma in children, namely omalizumab, mepolizumab, benralizumab, dupilumab, and tezepelumab have been shown to be effective in terms of asthma control and exacerbation rate. However, to date, information is still lacking regarding its long-term use. As a result, data are frequently extrapolated from adult studies. Thus, the selection of the appropriate biologic agent, the potential predictors of good asthma response, and the long-term outcome in the pediatric population are still to be further investigated. The aim of the present study was to provide an overview of the current status of the latest evidence about all licensed monoclonal antibodies (mAbs) that have emerged and been applied to the field of asthma management. The innovative future targets are also briefly discussed. Full article

(This article belongs to the Special Issue Asthma: From Phenotypes to Personalized Medicine)

14 pages, 292 KiB

Open AccessEditor’s ChoiceReview

Biological Therapy of Severe Asthma and Nasal Polyps

by Agamemnon Bakakos, Florence Schleich and Petros Bakakos

J. Pers. Med. 2022, 12(6), 976; https://doi.org/10.3390/jpm12060976 - 16 Jun 2022

Cited by 18 | Viewed by 4895

Abstract

Chronic rhinosinusitis is a common disease worldwide and can be categorized into chronic rhinosinusitis with nasal polyps and chronic rhinosinusitis without nasal polyps. Chronic rhinosinusitis with nasal polyps is common in patients with asthma and, particularly, severe asthma. Severe asthma is effectively treated [...] Read more.

Chronic rhinosinusitis is a common disease worldwide and can be categorized into chronic rhinosinusitis with nasal polyps and chronic rhinosinusitis without nasal polyps. Chronic rhinosinusitis with nasal polyps is common in patients with asthma and, particularly, severe asthma. Severe asthma is effectively treated with biologics and the coexistence of severe asthma with chronic rhinosinusitis with nasal polyps presents a phenotype that is more likely to respond to such treatment. In this review, we focus on the link between asthma and nasal polyps, and we review the treatment effect of various monoclonal antibodies in patients with severe asthma and nasal polyps as well as in patients with nasal polyps without asthma or with mild-to-moderate asthma. With the enhancement of our armamentarium with new monoclonal antibodies the right choice of biologic becomes an important target and one that is difficult to achieve due to the lack of comparative head-to-head studies. Full article

(This article belongs to the Special Issue Asthma: From Phenotypes to Personalized Medicine)

16 pages, 612 KiB

Open AccessEditor’s ChoiceReview

Gender and Autoimmune Liver Diseases: Relevant Aspects in Clinical Practice

by Federica Invernizzi, Marta Cilla, Silvia Trapani, Maria Guarino, Valentina Cossiga, Martina Gambato, Maria Cristina Morelli, Filomena Morisco, Patrizia Burra and Annarosa Floreani

J. Pers. Med. 2022, 12(6), 925; https://doi.org/10.3390/jpm12060925 - 2 Jun 2022

Cited by 17 | Viewed by 3075

Abstract

Autoimmune liver diseases (AILDs) include autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis. The etiologies of AILD are not well understood but appear to involve a combination of genetic and environmental factors. AILDs commonly affect young individuals and are characterized by a [...] Read more.

Autoimmune liver diseases (AILDs) include autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis. The etiologies of AILD are not well understood but appear to involve a combination of genetic and environmental factors. AILDs commonly affect young individuals and are characterized by a highly variable clinical course. These diseases significantly influence quality of life and can progress toward liver decompensation or the onset of hepatocellular or cholangiocarcinoma; a significant number of patients eventually progress to end-stage liver disease, requiring liver transplantation. In this review, we focus on the sex characteristics and peculiarities of AILD patients and highlight the relevance of a sex-specific analysis in future studies. Understanding the sex differences underlying AILD immune dysregulation may be critical for developing more effective treatments. Full article

(This article belongs to the Special Issue Personalized Medicine Interdisciplinary Aspects and Sex Gender-Specific Differences)

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17 pages, 784 KiB

Open AccessEditor’s ChoiceReview

by Mirabela Romanescu, Valentina Buda, Adelina Lombrea, Minodora Andor, Ionut Ledeti, Maria Suciu, Corina Danciu, Cristina Adriana Dehelean and Liana Dehelean

J. Pers. Med. 2022, 12(6), 907; https://doi.org/10.3390/jpm12060907 - 31 May 2022

Cited by 24 | Viewed by 5832

Abstract

In the last decades, both animal and human studies have neglected female subjects with the aim of evading a theorized intricacy of feminine hormonal status. However, clinical experience proves that pharmacological response may vary between the two sexes since pathophysiological dissimilarities between men [...] Read more.

In the last decades, both animal and human studies have neglected female subjects with the aim of evading a theorized intricacy of feminine hormonal status. However, clinical experience proves that pharmacological response may vary between the two sexes since pathophysiological dissimilarities between men and women significantly influence the pharmacokinetics and pharmacodynamics of drugs. Sex-related differences in central nervous system (CNS) medication are particularly challenging to assess due to the complexity of disease manifestation, drugs’ intricate mechanisms of action, and lack of trustworthy means of evaluating the clinical response to medication. Although many studies showed contrary results, it appears to be a general tendency towards a certain sex-related difference in each pharmacological class. Broadly, opioids seem to produce better analgesia in women especially when they are administered for a prolonged period of time. On the other hand, respiratory and gastrointestinal adverse drug reactions (ADRs) following morphine therapy are more prevalent among female patients. Regarding antidepressants, studies suggest that males might respond better to tricyclic antidepressants (TCAs), whereas females prefer selective serotonin reuptake inhibitors (SSRI), probably due to their tolerance to particular ADRs. In general, studies missed spotting any significant sex-related differences in the therapeutic effect of antiepileptic drugs (AED), but ADRs have sex variations in conjunction with sex hormones’ metabolism. On the subject of antipsychotic therapy, women appear to have a superior response to this pharmacological class, although there are also studies claiming the opposite. However, it seems that reported sex-related differences regarding ADRs are steadier: women are more at risk of developing various side effects, such as metabolic dysfunctions, cardiovascular disorders, and hyperprolactinemia. Taking all of the above into account, it seems that response to CNS drugs might be occasionally influenced by sex as a biological variable. Nonetheless, although for each pharmacological class, studies generally converge to a certain pattern, opposite outcomes are standing in the way of a clear consensus. Hence, the fact that so many studies are yielding conflicting results emphasizes once again the need to address sex-related differences in pharmacological response to drugs. Full article

(This article belongs to the Special Issue Personalized Treatment and Diagnosis Strategies in Psychiatry)

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13 pages, 1849 KiB

Open AccessEditor’s ChoiceReview

Digital Anthropometry for Body Circumference Measurements: European Phenotypic Variations throughout the Decades

by Marco Alessandro Minetto, Angelo Pietrobelli, Chiara Busso, Jonathan P. Bennett, Andrea Ferraris, John A. Shepherd and Steven B. Heymsfield

J. Pers. Med. 2022, 12(6), 906; https://doi.org/10.3390/jpm12060906 - 30 May 2022

Cited by 21 | Viewed by 4916

Abstract

This review summarizes body circumference-based anthropometrics that are in common use for research and in some cases clinical application. These include waist and hip circumference-based central body indices to predict cardiometabolic risk: waist circumference, waist-to-hip ratio, waist-to-height ratio, waist-to-thigh ratio, body adiposity index, [...] Read more.

This review summarizes body circumference-based anthropometrics that are in common use for research and in some cases clinical application. These include waist and hip circumference-based central body indices to predict cardiometabolic risk: waist circumference, waist-to-hip ratio, waist-to-height ratio, waist-to-thigh ratio, body adiposity index, a body shape index (ABSI), hip index (HI), and body roundness index (BRI). Limb circumference measurements are most often used to assess sarcopenia and include: thigh circumference, calf circumference, and mid-arm circumference. Additionally, this review presents fascinating recent developments in optic-based imaging technologies that have elucidated changes over the last decades in average body size and shape in European populations. The classical apple and pear shape concepts of body shape difference remain useful, but novel and exciting 3-D optical “e-taper” measurements provide a potentially powerful new future vista in anthropometrics. Full article

(This article belongs to the Special Issue Personalized Medicine Interdisciplinary Aspects and Sex Gender-Specific Differences)

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22 pages, 855 KiB

Open AccessEditor’s ChoiceReview

From Skin Barrier Dysfunction to Systemic Impact of Atopic Dermatitis: Implications for a Precision Approach in Dermocosmetics and Medicine

by Laura Maintz, Thomas Bieber, Helen D. Simpson and Anne-Laure Demessant-Flavigny

J. Pers. Med. 2022, 12(6), 893; https://doi.org/10.3390/jpm12060893 - 28 May 2022

Cited by 14 | Viewed by 4447

Abstract

Atopic dermatitis (AD) affects up to 20% of children and is considered the starting point of the atopic march with the development of food allergy, asthma, and allergic rhinitis. The heterogeneous phenotype reflects distinct and/or overlapping pathogenetic mechanisms with varying degrees of epidermal [...] Read more.

Atopic dermatitis (AD) affects up to 20% of children and is considered the starting point of the atopic march with the development of food allergy, asthma, and allergic rhinitis. The heterogeneous phenotype reflects distinct and/or overlapping pathogenetic mechanisms with varying degrees of epidermal barrier disruption, activation of different T cell subsets and dysbiosis of the skin microbiome. Here, we review current evidence suggesting a systemic impact of the cutaneous inflammation in AD together with a higher risk of asthma and other comorbidities, especially in severe and persistent AD. Thus, early therapy of AD to restore the impaired skin barrier, modified microbiome, and target type 2 inflammation, depending on the (endo)phenotype, in a tailored approach is crucial. We discuss what we can learn from the comorbidities and the implications for preventive and therapeutic interventions from precision dermocosmetics to precision medicine. The stratification of AD patients into biomarker-based endotypes for a precision medicine approach offers opportunities for better long-term control of AD with the potential to reduce the systemic impact of a chronic skin inflammation and even prevent or modify the course, not only of AD, but possibly also the comorbidities, depending on the patient’s age and disease stage. Full article

(This article belongs to the Special Issue Precision Medicine in Childhood Asthma)

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22 pages, 1899 KiB

Open AccessEditor’s ChoiceReview

CFTR and Gastrointestinal Cancers: An Update

by Rahul Bhattacharya, Zachary Blankenheim, Patricia M. Scott and Robert T. Cormier

J. Pers. Med. 2022, 12(6), 868; https://doi.org/10.3390/jpm12060868 - 25 May 2022

Cited by 14 | Viewed by 3900

Abstract

Cystic Fibrosis (CF) is a disease caused by mutations in the CFTR gene that severely affects the lungs as well as extra-pulmonary tissues, including the gastrointestinal (GI) tract. CFTR dysfunction resulting from either mutations or the downregulation of its expression has been shown [...] Read more.

Cystic Fibrosis (CF) is a disease caused by mutations in the CFTR gene that severely affects the lungs as well as extra-pulmonary tissues, including the gastrointestinal (GI) tract. CFTR dysfunction resulting from either mutations or the downregulation of its expression has been shown to promote carcinogenesis. An example is the enhanced risk for several types of cancer in patients with CF, especially cancers of the GI tract. CFTR also acts as a tumor suppressor in diverse sporadic epithelial cancers in many tissues, primarily due to the silencing of CFTR expression via multiple mechanisms, but especially due to epigenetic regulation. This review provides an update on the latest research linking CFTR-deficiency to GI cancers, in both CF patients and in sporadic GI cancers, with a particular focus on cancer of the intestinal tract. It will discuss changes in the tissue landscape linked to CFTR-deficiency that may promote cancer development such as breakdowns in physical barriers, microbial dysbiosis and inflammation. It will also discuss molecular pathways and mechanisms that act upstream to modulate CFTR expression, such as by epigenetic silencing, as well as molecular pathways that act downstream of CFTR-deficiency, such as the dysregulation of the Wnt/β-catenin and NF-κB signaling pathways. Finally, it will discuss the emerging CFTR modulator drugs that have shown promising results in improving CFTR function in CF patients. The potential impact of these modulator drugs on the treatment and prevention of GI cancers can provide a new example of personalized cancer medicine. Full article

(This article belongs to the Special Issue Cystic Fibrosis: Diagnosis, Treatment, and Related Disorders)

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22 pages, 3223 KiB

Open AccessEditor’s ChoiceReview

Precision Medicine in Head and Neck Cancers: Genomic and Preclinical Approaches

by Giacomo Miserocchi, Chiara Spadazzi, Sebastiano Calpona, Francesco De Rosa, Alice Usai, Alessandro De Vita, Chiara Liverani, Claudia Cocchi, Silvia Vanni, Chiara Calabrese, Massimo Bassi, Giovanni De Luca, Giuseppe Meccariello, Toni Ibrahim, Marco Schiavone and Laura Mercatali

J. Pers. Med. 2022, 12(6), 854; https://doi.org/10.3390/jpm12060854 - 24 May 2022

Cited by 19 | Viewed by 3702

Abstract

Head and neck cancers (HNCs) represent the sixth most widespread malignancy worldwide. Surgery, radiotherapy, chemotherapeutic and immunotherapeutic drugs represent the main clinical approaches for HNC patients. Moreover, HNCs are characterised by an elevated mutational load; however, specific genetic mutations or biomarkers have not [...] Read more.

Head and neck cancers (HNCs) represent the sixth most widespread malignancy worldwide. Surgery, radiotherapy, chemotherapeutic and immunotherapeutic drugs represent the main clinical approaches for HNC patients. Moreover, HNCs are characterised by an elevated mutational load; however, specific genetic mutations or biomarkers have not yet been found. In this scenario, personalised medicine is showing its efficacy. To study the reliability and the effects of personalised treatments, preclinical research can take advantage of next-generation sequencing and innovative technologies that have been developed to obtain genomic and multi-omic profiles to drive personalised treatments. The crosstalk between malignant and healthy components, as well as interactions with extracellular matrices, are important features which are responsible for treatment failure. Preclinical research has constantly implemented in vitro and in vivo models to mimic the natural tumour microenvironment. Among them, 3D systems have been developed to reproduce the tumour mass architecture, such as biomimetic scaffolds and organoids. In addition, in vivo models have been changed over the last decades to overcome problems such as animal management complexity and time-consuming experiments. In this review, we will explore the new approaches aimed to improve preclinical tools to study and apply precision medicine as a therapeutic option for patients affected by HNCs. Full article

(This article belongs to the Special Issue Personalized Medicine in Cancer Therapy: Mechanism, Approaches and Techniques)

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22 pages, 982 KiB

Open AccessEditor’s ChoiceReview

Personalized Management of Patients with Chronic Rhinosinusitis with Nasal Polyps in Clinical Practice: A Multidisciplinary Consensus Statement

by Eugenio De Corso, Maria Beatrice Bilò, Andrea Matucci, Veronica Seccia, Fulvio Braido, Matteo Gelardi, Enrico Heffler, Manuela Latorre, Luca Malvezzi, Girolamo Pelaia, Gianenrico Senna, Paolo Castelnuovo and Giorgio Walter Canonica

J. Pers. Med. 2022, 12(5), 846; https://doi.org/10.3390/jpm12050846 - 23 May 2022

Cited by 16 | Viewed by 4715

Abstract

Chronic rhinosinusitis (CRS) is a sino-nasal chronic inflammatory disease, occurring in 5–15% of the general population. CRS with nasal polyps (CRSwNP) is present in up to 30% of the CRS population. One-third of CRSwNP patients suffer from disease that is uncontrolled by current [...] Read more.

Chronic rhinosinusitis (CRS) is a sino-nasal chronic inflammatory disease, occurring in 5–15% of the general population. CRS with nasal polyps (CRSwNP) is present in up to 30% of the CRS population. One-third of CRSwNP patients suffer from disease that is uncontrolled by current standards of care. Biologics are an emerging treatment option for patients with severe uncontrolled CRSwNP, but their positioning in the treatment algorithm is under discussion. Effective endotyping of CRSwNP patients who could benefit from biologics treatment is required, as suggested by international guidelines. Other issues affecting management include comorbidities, such as allergy, non-steroidal anti-inflammatory drug–exacerbated respiratory disease, and asthma. Therefore, the choice of treatment in CRSwNP patients depends on many factors. A multidisciplinary approach may improve CRSwNP management in patients with comorbidities, but currently there is no shared management model. We summarize the outcomes of a Delphi process involving a multidisciplinary panel of otolaryngologists, pulmonologists, and allergist-immunologists involved in the management of CRSwNP, who attempted to reach consensus on key statements relating to the diagnosis, endotyping, classification and management (including the place of biologics) of CRSwNP patients. Full article

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

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13 pages, 869 KiB

Open AccessEditor’s ChoiceReview

Paucigranulocytic Asthma: Potential Pathogenetic Mechanisms, Clinical Features and Therapeutic Management

by Andriana I. Papaioannou, Evangelia Fouka, Polyxeni Ntontsi, Grigoris Stratakos and Spyridon Papiris

J. Pers. Med. 2022, 12(5), 850; https://doi.org/10.3390/jpm12050850 - 23 May 2022

Cited by 10 | Viewed by 3565

Abstract

Asthma is a heterogeneous disease usually characterized by chronic airway inflammation, in which several phenotypes have been described, related to the age of onset, symptoms, inflammatory characteristics and treatment response. The identification of the inflammatory phenotype in asthma is very useful, since it [...] Read more.

Asthma is a heterogeneous disease usually characterized by chronic airway inflammation, in which several phenotypes have been described, related to the age of onset, symptoms, inflammatory characteristics and treatment response. The identification of the inflammatory phenotype in asthma is very useful, since it allows for both the recognition of the asthmatic triggering factor as well as the optimization of treatment The paucigranulocytic phenotype of asthma (PGA) is characterized by sputum eosinophil levels <1–3% and sputum neutrophil levels < 60%. The precise characteristics and the pathobiology of PGA are not fully understood, and, in some cases, it seems to represent a previous eosinophilic phenotype with a good response to anti-inflammatory treatment. However, many patients with PGA remain uncontrolled and experience asthmatic symptoms and exacerbations, irrespective of the low grade of airway inflammation. This observation leads to the hypothesis that PGA might also be either a special phenotype driven by different kinds of cells, such as macrophages or mast cells, or a non-inflammatory phenotype with a low grade of eosinophilic inflammation. In this review, we aim to describe the special characteristics of PGA and the potential therapeutic interventions that could be offered to these patients. Full article

(This article belongs to the Special Issue Asthma: From Phenotypes to Personalized Medicine)

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28 pages, 2862 KiB

Open AccessEditor’s ChoiceReview

Diffuse Intrinsic Pontine Glioma: Molecular Landscape, Evolving Treatment Strategies and Emerging Clinical Trials

by Sudarshawn Damodharan, Montserrat Lara-Velazquez, Brooke Carmen Williamsen, Jeffrey Helgager and Mahua Dey

J. Pers. Med. 2022, 12(5), 840; https://doi.org/10.3390/jpm12050840 - 20 May 2022

Cited by 23 | Viewed by 8295

Abstract

Diffuse intrinsic pontine glioma (DIPG) is a type of intrinsic brainstem glial tumor that occurs primarily in the pediatric population. DIPG is initially diagnosed based on clinical symptoms and the characteristic location on imaging. Histologically, these tumors are characterized by a heterogenous population [...] Read more.

Diffuse intrinsic pontine glioma (DIPG) is a type of intrinsic brainstem glial tumor that occurs primarily in the pediatric population. DIPG is initially diagnosed based on clinical symptoms and the characteristic location on imaging. Histologically, these tumors are characterized by a heterogenous population of cells with multiple genetic mutations and high infiltrative capacity. The most common mutation seen in this group is a lysine to methionine point mutation seen at position 27 (K27M) within histone 3 (H3). Tumors with the H3 K27M mutation, are considered grade 4 and are now categorized within the H3 K27-altered diffuse midline glioma category by World Health Organization classification. Due to its critical location and aggressive nature, DIPG is resistant to the most eradicative treatment and is universally fatal; however, modern advances in the surgical techniques resulting in safe biopsy of the lesion have significantly improved our understanding of this disease at the molecular level. Genomic analysis has shown several mutations that play a role in the pathophysiology of the disease and can be targeted therapeutically. In this review, we will elaborate on DIPG from general aspects and the evolving molecular landscape. We will also review innovative therapeutic options that have been trialed along with new promising treatments on the horizon. Full article

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

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29 pages, 1462 KiB

Open AccessEditor’s ChoiceReview

Dysregulated miRNAs as Biomarkers and Therapeutical Targets in Neurodegenerative Diseases

by Giulia Gentile, Giovanna Morello, Valentina La Cognata, Maria Guarnaccia, Francesca Luisa Conforti and Sebastiano Cavallaro

J. Pers. Med. 2022, 12(5), 770; https://doi.org/10.3390/jpm12050770 - 10 May 2022

Cited by 32 | Viewed by 5974

Abstract

Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS) are representative neurodegenerative diseases (NDs) characterized by degeneration of selective neurons, as well as the lack of effective biomarkers and therapeutic treatments. In the last decade, microRNAs (miRNAs) have gained considerable interest [...] Read more.

Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS) are representative neurodegenerative diseases (NDs) characterized by degeneration of selective neurons, as well as the lack of effective biomarkers and therapeutic treatments. In the last decade, microRNAs (miRNAs) have gained considerable interest in diagnostics and therapy of NDs, owing to their aberrant expression and their ability to target multiple molecules and pathways. Here, we provide an overview of dysregulated miRNAs in fluids (blood or cerebrospinal fluid) and nervous tissue of AD, PD, and ALS patients. By emphasizing those that are commonly dysregulated in these NDs, we highlight their potential role as biomarkers or therapeutical targets and describe the use of antisense oligonucleotides as miRNA therapies. Full article

(This article belongs to the Section Omics/Informatics)

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21 pages, 472 KiB

Open AccessEditor’s ChoiceReview

Non-Pharmacological Nursing Interventions to Prevent Delirium in ICU Patients—An Umbrella Review with Implications for Evidence-Based Practice

by Sandra Lange, Wioletta Mędrzycka-Dąbrowska, Adriano Friganovic, Ber Oomen and Sabina Krupa

J. Pers. Med. 2022, 12(5), 760; https://doi.org/10.3390/jpm12050760 - 7 May 2022

Cited by 14 | Viewed by 11734

Abstract

Delirium in ICU patients is a complication associated with many adverse consequences. Given the high prevalence of this complication in critically ill patients, it is essential to develop and implement an effective management protocol to prevent delirium. Given that the cause of delirium [...] Read more.

Delirium in ICU patients is a complication associated with many adverse consequences. Given the high prevalence of this complication in critically ill patients, it is essential to develop and implement an effective management protocol to prevent delirium. Given that the cause of delirium is multifactorial, non-pharmacological multicomponent interventions are promising strategies for delirium prevention. (1) Background: To identify and evaluate published systematic review on non-pharmacological nursing interventions to prevent delirium in intensive care unit patients. (2) Methods: An umbrella review guided by the Joanna Briggs Institute was utilized. Data were obtained from PubMed, Scopus, EBSCO, Web of Science, Cochrane Library, and Google Scholar. The last search was conducted on 1 May 2022. (3) Results: Fourteen reviews met the inclusion criteria. Multicomponent interventions are the most promising methods in the fight against delirium. The patient’s family is an important part of the process and should be included in the delirium prevention scheme. Light therapy can improve the patient’s circadian rhythm and thus contribute to reducing the incidence of delirium. (4) Conclusions: Non-pharmacological nursing interventions may be effective in preventing and reducing the duration of delirium in ICU patients. Full article

(This article belongs to the Special Issue Advances in Personalized Nursing Care)

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18 pages, 4822 KiB

Open AccessEditor’s ChoiceReview

FFPE-Based NGS Approaches into Clinical Practice: The Limits of Glory from a Pathologist Viewpoint

by Filippo Cappello, Valentina Angerilli, Giada Munari, Carlotta Ceccon, Marianna Sabbadin, Fabio Pagni, Nicola Fusco, Umberto Malapelle and Matteo Fassan

J. Pers. Med. 2022, 12(5), 750; https://doi.org/10.3390/jpm12050750 - 5 May 2022

Cited by 19 | Viewed by 5417

Abstract

The introduction of next-generation sequencing (NGS) in the molecular diagnostic armamentarium is deeply changing pathology practice and laboratory frameworks. NGS allows for the comprehensive molecular characterization of neoplasms, in order to provide the best treatment to oncologic patients. On the other hand, NGS [...] Read more.

The introduction of next-generation sequencing (NGS) in the molecular diagnostic armamentarium is deeply changing pathology practice and laboratory frameworks. NGS allows for the comprehensive molecular characterization of neoplasms, in order to provide the best treatment to oncologic patients. On the other hand, NGS raises technical issues and poses several challenges in terms of education, infrastructures and costs. The aim of this review is to give an overview of the main NGS sequencing platforms that can be used in current molecular diagnostics and gain insights into the clinical applications of NGS in precision oncology. Hence, we also focus on the preanalytical, analytical and interpretative issues raised by the incorporation of NGS in routine pathology diagnostics. Full article

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

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15 pages, 635 KiB

Open AccessEditor’s ChoiceReview

Asthma-COPD Overlap Syndrome: Recent Insights and Unanswered Questions

by Evangelia Fouka, Andriana I. Papaioannou, Georgios Hillas and Paschalis Steiropoulos

J. Pers. Med. 2022, 12(5), 708; https://doi.org/10.3390/jpm12050708 - 28 Apr 2022

Cited by 16 | Viewed by 4361

Abstract

The term asthma-COPD overlap (ACO) has been used to identify a heterogeneous condition in which patients present with airflow limitation that is not completely reversible and clinical and inflammatory features of both asthma and chronic obstructive pulmonary disease (COPD). ACO diagnosis may be [...] Read more.

The term asthma-COPD overlap (ACO) has been used to identify a heterogeneous condition in which patients present with airflow limitation that is not completely reversible and clinical and inflammatory features of both asthma and chronic obstructive pulmonary disease (COPD). ACO diagnosis may be difficult in clinical practice, while controversy still exists regarding its definition, pathophysiology, and impact. Patients with ACO experience a greater disease burden compared to patients with asthma or COPD alone, but in contrast they show better response to inhaled corticosteroid treatment than other COPD phenotypes. Current management recommendations focus on defining specific and measurable treatable clinical traits, according to disease phenotypes and underlying biological mechanisms for every single patient. In this publication, we review the current knowledge on definition, pathophysiology, clinical characteristics, and management options of ACO. Full article

(This article belongs to the Special Issue Asthma: From Phenotypes to Personalized Medicine)

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19 pages, 2807 KiB

Open AccessEditor’s ChoiceReview

Endotypes of Prematurity and Phenotypes of Bronchopulmonary Dysplasia: Toward Personalized Neonatology

by Maria Pierro, Karen Van Mechelen, Elke van Westering-Kroon, Eduardo Villamor-Martínez and Eduardo Villamor

J. Pers. Med. 2022, 12(5), 687; https://doi.org/10.3390/jpm12050687 - 26 Apr 2022

Cited by 29 | Viewed by 8044

Abstract

Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, is increasingly recognized as the consequence of a pathological reparative response of the developing lung to both antenatal and postnatal injury. According to this view, the pathogenesis of BPD is multifactorial and heterogeneous with [...] Read more.

Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, is increasingly recognized as the consequence of a pathological reparative response of the developing lung to both antenatal and postnatal injury. According to this view, the pathogenesis of BPD is multifactorial and heterogeneous with different patterns of antenatal stress (endotypes) that combine with varying postnatal insults and might distinctively damage the development of airways, lung parenchyma, interstitium, lymphatic system, and pulmonary vasculature. This results in different clinical phenotypes of BPD. There is no clear consensus on which are the endotypes of prematurity but the combination of clinical information with placental and bacteriological data enables the identification of two main pathways leading to birth before 32 weeks of gestation: (1) infection/inflammation and (2) dysfunctional placentation. Regarding BPD phenotypes, the following have been proposed: parenchymal, peripheral airway, central airway, interstitial, congestive, vascular, and mixed phenotype. In line with the approach of personalized medicine, endotyping prematurity and phenotyping BPD will facilitate the design of more targeted therapeutic and prognostic approaches. Full article

(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Pulmonary Diseases)

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14 pages, 2645 KiB

Open AccessEditor’s ChoiceReview

Should Neurosurgeons Try to Preserve Non-Traditional Brain Networks? A Systematic Review of the Neuroscientific Evidence

by Nicholas B. Dadario and Michael E. Sughrue

J. Pers. Med. 2022, 12(4), 587; https://doi.org/10.3390/jpm12040587 - 6 Apr 2022

Cited by 23 | Viewed by 4274

Abstract

The importance of large-scale brain networks in higher-order human functioning is well established in neuroscience, but has yet to deeply penetrate neurosurgical thinking due to concerns of clinical relevance. Here, we conducted the first systematic review examining the clinical importance of non-traditional, large-scale [...] Read more.

The importance of large-scale brain networks in higher-order human functioning is well established in neuroscience, but has yet to deeply penetrate neurosurgical thinking due to concerns of clinical relevance. Here, we conducted the first systematic review examining the clinical importance of non-traditional, large-scale brain networks, including the default mode (DMN), central executive (CEN), salience (SN), dorsal attention (DAN), and ventral attention (VAN) networks. Studies which reported evidence of neurologic, cognitive, or emotional deficits in relation to damage or dysfunction in these networks were included. We screened 22,697 articles on PubMed, and 551 full-text articles were included and examined. Cognitive deficits were the most common symptom of network disturbances in varying amounts (36–56%), most frequently related to disruption of the DMN (n = 213) or some combination of DMN, CEN, and SN networks (n = 182). An increased proportion of motor symptoms was seen with CEN disruption (12%), and emotional (35%) or language/speech deficits (24%) with SN disruption. Disruption of the attention networks (VAN/DAN) with each other or the other networks mostly led to cognitive deficits (56%). A large body of evidence is available demonstrating the clinical importance of non-traditional, large-scale brain networks and suggests the need to preserve these networks is relevant for neurosurgical patients. Full article

(This article belongs to the Special Issue Personalized Medicine in Neurological and Neurosurgical Diseases)

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17 pages, 708 KiB

Open AccessEditor’s ChoiceReview

Emerging Biomarkers for Early Detection of Chronic Kidney Disease

by Maja Mizdrak, Marko Kumrić, Tina Tičinović Kurir and Joško Božić

J. Pers. Med. 2022, 12(4), 548; https://doi.org/10.3390/jpm12040548 - 31 Mar 2022

Cited by 44 | Viewed by 9459

Abstract

Chronic kidney disease (CKD) is a major and serious global health problem that leads to kidney damage as well as multiple systemic diseases. Early diagnosis and treatment are two major measures to prevent further deterioration of kidney function and to delay adverse outcomes. [...] Read more.

Chronic kidney disease (CKD) is a major and serious global health problem that leads to kidney damage as well as multiple systemic diseases. Early diagnosis and treatment are two major measures to prevent further deterioration of kidney function and to delay adverse outcomes. However, the paucity of early, predictive and noninvasive biomarkers has undermined our ability to promptly detect and treat this common clinical condition which affects more than 10% of the population worldwide. Despite all limitations, kidney function is still measured by serum creatinine, cystatin C, and albuminuria, as well as estimating glomerular filtration rate using different equations. This review aims to provide comprehensive insight into diagnostic methods available for early detection of CKD. In the review, we discuss the following topics: (i) markers of glomerular injury; (ii) markers of tubulointerstitial injury; (iii) the role of omics; (iv) the role of microbiota; (v) and finally, the role of microRNA in the early detection of CKD. Despite all novel findings, none of these biomarkers have met the criteria of an ideal early marker. Since the central role in CKD progression is the proximal tubule (PT), most data from the literature have analyzed biomarkers of PT injury, such as KIM-1 (kidney injury molecule-1), NGAL (neutrophil gelatinase-associated lipocalin), and L-FABP (liver fatty acid-binding protein). Full article

(This article belongs to the Special Issue Chronic Kidney Disease: Early Detection, Mechanisms, and Therapeutic Implications)

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24 pages, 1096 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Artificial Intelligence-Driven Prediction Modeling and Decision Making in Spine Surgery Using Hybrid Machine Learning Models

by Babak Saravi, Frank Hassel, Sara Ülkümen, Alisia Zink, Veronika Shavlokhova, Sebastien Couillard-Despres, Martin Boeker, Peter Obid and Gernot Michael Lang

J. Pers. Med. 2022, 12(4), 509; https://doi.org/10.3390/jpm12040509 - 22 Mar 2022

Cited by 63 | Viewed by 8372

Abstract

Healthcare systems worldwide generate vast amounts of data from many different sources. Although of high complexity for a human being, it is essential to determine the patterns and minor variations in the genomic, radiological, laboratory, or clinical data that reliably differentiate phenotypes or [...] Read more.

Healthcare systems worldwide generate vast amounts of data from many different sources. Although of high complexity for a human being, it is essential to determine the patterns and minor variations in the genomic, radiological, laboratory, or clinical data that reliably differentiate phenotypes or allow high predictive accuracy in health-related tasks. Convolutional neural networks (CNN) are increasingly applied to image data for various tasks. Its use for non-imaging data becomes feasible through different modern machine learning techniques, converting non-imaging data into images before inputting them into the CNN model. Considering also that healthcare providers do not solely use one data modality for their decisions, this approach opens the door for multi-input/mixed data models which use a combination of patient information, such as genomic, radiological, and clinical data, to train a hybrid deep learning model. Thus, this reflects the main characteristic of artificial intelligence: simulating natural human behavior. The present review focuses on key advances in machine and deep learning, allowing for multi-perspective pattern recognition across the entire information set of patients in spine surgery. This is the first review of artificial intelligence focusing on hybrid models for deep learning applications in spine surgery, to the best of our knowledge. This is especially interesting as future tools are unlikely to use solely one data modality. The techniques discussed could become important in establishing a new approach to decision-making in spine surgery based on three fundamental pillars: (1) patient-specific, (2) artificial intelligence-driven, (3) integrating multimodal data. The findings reveal promising research that already took place to develop multi-input mixed-data hybrid decision-supporting models. Their implementation in spine surgery may hence be only a matter of time. Full article

(This article belongs to the Special Issue Application of Artificial Intelligence in Personalized Medicine)

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14 pages, 613 KiB

Open AccessEditor’s ChoiceReview

Focus on Sex and Gender: What We Need to Know in the Management of Rheumatoid Arthritis

by Beatrice Maranini, Alessandra Bortoluzzi, Ettore Silvagni and Marcello Govoni

J. Pers. Med. 2022, 12(3), 499; https://doi.org/10.3390/jpm12030499 - 20 Mar 2022

Cited by 37 | Viewed by 9865

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease, affecting mostly women with a female/male ratio of 3:1. It is characterized by symmetrical polyarthritis, leading to progressive joint damage. Sex differences have been reported in terms of disease course and characteristics, influencing patients reported [...] Read more.

Rheumatoid arthritis (RA) is a chronic inflammatory disease, affecting mostly women with a female/male ratio of 3:1. It is characterized by symmetrical polyarthritis, leading to progressive joint damage. Sex differences have been reported in terms of disease course and characteristics, influencing patients reported outcome measures (PROMs) and pain perception, ultimately leading to male–female disparities in treatment response. Notwithstanding, sex and gender discrepancies are still under-reported in clinical trials. Therefore, there is a consistent need for a precise reference of sex and gender issues in RA studies to improve treat-to-target achievement. This narrative review explores the above-mentioned aspects of RA disease, discussing the latest core principles of RA recommendations, from safety issues to early arthritis concept and management, treat-to-target and difficult-to-treat notions, up to the most recent debate on vaccination. Our final purpose is to evaluate how sex and gender can impact current management guidelines and how this issue can be integrated for effective disease control. Full article

(This article belongs to the Special Issue Personalized Medicine Interdisciplinary Aspects and Sex Gender-Specific Differences)

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36 pages, 1280 KiB

Open AccessEditor’s ChoiceReview

Towards Machine Learning-Aided Lung Cancer Clinical Routines: Approaches and Open Challenges

by Francisco Silva, Tania Pereira, Inês Neves, Joana Morgado, Cláudia Freitas, Mafalda Malafaia, Joana Sousa, João Fonseca, Eduardo Negrão, Beatriz Flor de Lima, Miguel Correia da Silva, António J. Madureira, Isabel Ramos, José Luis Costa, Venceslau Hespanhol, António Cunha and Hélder P. Oliveira

J. Pers. Med. 2022, 12(3), 480; https://doi.org/10.3390/jpm12030480 - 16 Mar 2022

Cited by 25 | Viewed by 5274

Abstract

Advancements in the development of computer-aided decision (CAD) systems for clinical routines provide unquestionable benefits in connecting human medical expertise with machine intelligence, to achieve better quality healthcare. Considering the large number of incidences and mortality numbers associated with lung cancer, there is [...] Read more.

Advancements in the development of computer-aided decision (CAD) systems for clinical routines provide unquestionable benefits in connecting human medical expertise with machine intelligence, to achieve better quality healthcare. Considering the large number of incidences and mortality numbers associated with lung cancer, there is a need for the most accurate clinical procedures; thus, the possibility of using artificial intelligence (AI) tools for decision support is becoming a closer reality. At any stage of the lung cancer clinical pathway, specific obstacles are identified and “motivate” the application of innovative AI solutions. This work provides a comprehensive review of the most recent research dedicated toward the development of CAD tools using computed tomography images for lung cancer-related tasks. We discuss the major challenges and provide critical perspectives on future directions. Although we focus on lung cancer in this review, we also provide a more clear definition of the path used to integrate AI in healthcare, emphasizing fundamental research points that are crucial for overcoming current barriers. Full article

(This article belongs to the Special Issue Personalized Medicine in Lung Cancer: Diagnosis, Treatment and Prognosis)

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22 pages, 2248 KiB

Open AccessEditor’s ChoiceReview

Dental and Skeletal Side Effects of Oral Appliances Used for the Treatment of Obstructive Sleep Apnea and Snoring in Adult Patients—A Systematic Review and Meta-Analysis

by Ioannis A. Tsolakis, Juan Martin Palomo, Stefanos Matthaios and Apostolos I. Tsolakis

J. Pers. Med. 2022, 12(3), 483; https://doi.org/10.3390/jpm12030483 - 16 Mar 2022

Cited by 15 | Viewed by 4750

Abstract

Background: Mandibular advancement devices for obstructive sleep apnea treatment are becoming increasingly popular among patients who do not prefer CPAP devices or surgery. Our study aims to evaluate the literature regarding potential dental and skeletal side effects caused by mandibular advancement appliances used [...] Read more.

Background: Mandibular advancement devices for obstructive sleep apnea treatment are becoming increasingly popular among patients who do not prefer CPAP devices or surgery. Our study aims to evaluate the literature regarding potential dental and skeletal side effects caused by mandibular advancement appliances used for adult OSA treatment. Methods: Electronic databases were searched for published and unpublished literature along with the reference lists of the eligible studies. Randomized clinical trials and non-randomized trials assessing dental and skeletal changes by comparing cephalometric radiographs were selected. Study selection, data extraction, and risk of bias assessment were performed individually and in duplicate. Fourteen articles were finally selected (two randomized clinical trials and 12 non-randomized trials). Results: The results suggest that mandibular advancement devices used for OSA treatment increase the lower incisor proclination by 1.54 ± 0.16°, decrease overjet by 0.89 ± 0.04 mm and overbite by 0.68 ± 0.04 mm, rotate the mandible downward and forward, and increase the SNA angle by to 0.06 ± 0.03°. The meta-analysis revealed high statistical heterogeneity. Conclusions: The MADs affect the lower incisor proclination, overjet, overbite, the rotation of the mandible and the SNA angle. More randomized clinical trials providing high-quality evidence are needed to support those findings. Full article

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

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15 pages, 618 KiB

Open AccessEditor’s ChoiceReview

Sex Differences in Response to Treatment with Glucagon-like Peptide 1 Receptor Agonists: Opportunities for a Tailored Approach to Diabetes and Obesity Care

by Elpiniki Rentzeperi, Stavroula Pegiou, Theocharis Koufakis, Maria Grammatiki and Kalliopi Kotsa

J. Pers. Med. 2022, 12(3), 454; https://doi.org/10.3390/jpm12030454 - 13 Mar 2022

Cited by 43 | Viewed by 7994

Abstract

The available data suggest differences in the course of type 2 diabetes mellitus (T2DM) between men and women, influenced by the distinguishing features of the sex. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are a relatively new class of antidiabetic drugs that act [...] Read more.

The available data suggest differences in the course of type 2 diabetes mellitus (T2DM) between men and women, influenced by the distinguishing features of the sex. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are a relatively new class of antidiabetic drugs that act by mimicking the function of endogenous glucagon-like peptide 1. They constitute valuable agents for the management of T2DM as, in addition to exerting a strong hypoglycemic action, they present cardiorenal protective properties, promote weight loss, and have a good safety profile, particularly with respect to the risk of hypoglycemia. Due to the precedent of studies having identified sexual dimorphic elements regarding the action of other antidiabetic agents, ongoing research has attempted to examine whether this is also the case for GLP-1 RAs. Until now, sex differences have been observed in the impact of GLP1-RAs on glycemic control, weight reduction, and frequency of adverse events. On the contrary, the question of whether these drugs differentially affect the two sexes with respect to cardiovascular risk and incidence of major adverse cardiovascular events remains under investigation. Knowledge of the potential sex-specific effects of these medications is extremely useful for the implementation of individualized therapeutic plans in the treatment of T2DM. This narrative review aims to present the available data regarding the sex-specific action of GLP-1 RAs as well as to discuss the potential pathophysiologic mechanisms explaining these dissimilarities. Full article

(This article belongs to the Special Issue Obesity and Diabetes: Genetic Markers and Pharmacological Interventions)

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14 pages, 984 KiB

Open AccessEditor’s ChoiceReview

Current Status, Issues and Future Prospects of Personalized Medicine for Each Disease

by Yuichi Yamamoto, Norihiro Kanayama, Yusuke Nakayama and Nobuko Matsushima

J. Pers. Med. 2022, 12(3), 444; https://doi.org/10.3390/jpm12030444 - 11 Mar 2022

Cited by 24 | Viewed by 6527

Abstract

In recent years, with the advancement of next-generation sequencing (NGS) technology, gene panel tests have been approved in the field of cancer diseases, and approaches to prescribe optimal molecular target drugs to patients are being developed. In the field of rare diseases, whole-genome [...] Read more.

In recent years, with the advancement of next-generation sequencing (NGS) technology, gene panel tests have been approved in the field of cancer diseases, and approaches to prescribe optimal molecular target drugs to patients are being developed. In the field of rare diseases, whole-genome and whole-exome analysis has been used to identify the causative genes of undiagnosed diseases and to diagnose patients’ diseases, and further progress in personalized medicine is expected. In order to promote personalized medicine in the future, we investigated the current status and progress of personalized medicine in disease areas other than cancer and rare diseases, where personalized medicine is most advanced. We selected rheumatoid arthritis and psoriasis as the inflammatory disease, in addition to Alzheimer’s disease. These diseases have high unmet needs for personalized medicine from the viewpoints of disease mechanisms, diagnostic biomarkers, therapeutic drugs with diagnostic markers and treatment satisfaction. In rheumatoid arthritis and psoriasis, there are many therapeutic options; however, diagnostic methods have not been developed to select the best treatment for each patient. In addition, there are few effective therapeutic agents in Alzheimer’s disease, although clinical trials of many candidate drugs have been conducted. In rheumatoid arthritis and psoriasis, further elucidation of the disease mechanism is desired to enable the selection of appropriate therapeutic agents according to the patient profile. In the case of Alzheimer’s disease, progress in preventive medicine is desired through the establishment of an early diagnosis method as well as the research and development of innovative therapeutic agents. To this end, we hope for further research and development of diagnostic markers and new drugs through progress in comprehensive data analysis such as comprehensive genomic and transcriptomic information. Furthermore, new types of markers such as miRNAs and the gut microbiome are desired to be utilized in clinical diagnostics. Full article

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21 pages, 1084 KiB

Open AccessEditor’s ChoiceReview

A Scoping Review of Attitudes and Experiences with Pharmacogenomic Testing among Patients and the General Public: Implications for Patient Counseling

by Josiah D. Allen, Amy L. Pittenger and Jeffrey R. Bishop

J. Pers. Med. 2022, 12(3), 425; https://doi.org/10.3390/jpm12030425 - 9 Mar 2022

Cited by 15 | Viewed by 3188

Abstract

The use of pharmacogenomic (PGx) tests is increasing, but there are not standard approaches to counseling patients on their implications or results. To inform approaches for patient counseling, we conducted a scoping review of published literature on patient experiences with PGx testing and [...] Read more.

The use of pharmacogenomic (PGx) tests is increasing, but there are not standard approaches to counseling patients on their implications or results. To inform approaches for patient counseling, we conducted a scoping review of published literature on patient experiences with PGx testing and performed a thematic analysis of qualitative and quantitative reports. A structured scoping review was conducted using Joanna Briggs Institute guidance. The search identified 37 articles (involving n = 6252 participants) published between 2010 and 2021 from a diverse range of populations and using a variety of study methodologies. Thematic analysis identified five themes (reasons for testing/perceived benefit, understanding of results, psychological response, impact of testing on patient/provider relationship, concerns about testing/perceived harm) and 22 subthemes. These results provide valuable context and potential areas of focus during patient counseling on PGx. Many of the knowledge gaps, misunderstandings, and concerns that participants identified could be mitigated by pre- and post-test counseling. More research is needed on patients’ PGx literacy needs, along with the development of a standardized, open-source patient education curriculum and the development of validated PGx literacy assessment tools. Full article

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16 pages, 329 KiB

Open AccessEditor’s ChoiceReview

Incorporating Biomarkers in COPD Management: The Research Keeps Going

by Ioannis Pantazopoulos, Kalliopi Magounaki, Ourania Kotsiou, Erasmia Rouka, Fotis Perlikos, Sotirios Kakavas and Konstantinos Gourgoulianis

J. Pers. Med. 2022, 12(3), 379; https://doi.org/10.3390/jpm12030379 - 1 Mar 2022

Cited by 13 | Viewed by 4069

Abstract

Globally, chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality, having a significant socioeconomic effect. Several molecular mechanisms have been related to COPD including chronic inflammation, telomere shortening, and epigenetic modifications. Nowadays, there is an increasing need for novel [...] Read more.

Globally, chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality, having a significant socioeconomic effect. Several molecular mechanisms have been related to COPD including chronic inflammation, telomere shortening, and epigenetic modifications. Nowadays, there is an increasing need for novel therapeutic approaches for the management of COPD. These treatment strategies should be based on finding the source of acute exacerbation of COPD episodes and estimating the patient’s own risk. The use of biomarkers and the measurement of their levels in conjunction with COPD exacerbation risk and disease prognosis is considered an encouraging approach. Many types of COPD biomarkers have been identified which include blood protein biomarkers, cellular biomarkers, and protease enzymes. They have been isolated from different sources including peripheral blood, sputum, bronchoalveolar fluid, exhaled air, and genetic material. However, there is still not an exclusive biomarker that is used for the evaluation of COPD but rather a combination of them, and this is attributed to disease complexity. In this review, we summarize the clinical significance of COPD-related biomarkers, their association with disease outcomes, and COPD patients’ management. Finally, we depict the various samples that are used for identifying and measuring these biomarkers. Full article

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

15 pages, 2104 KiB

Open AccessEditor’s ChoiceReview

A Revised Stem Cell Theory for the Pathogenesis of Endometriosis

by Tetsuo Maruyama

J. Pers. Med. 2022, 12(2), 216; https://doi.org/10.3390/jpm12020216 - 4 Feb 2022

Cited by 22 | Viewed by 6231

Abstract

During the past decade, a stem cell-based hypothesis has emerged (among many others) to explain the pathogenesis of endometriosis. The initial hypothesis proposed that endometriosis arose from a single or a few specific cells with stem cell properties, including self-renewal and multi-lineage cell [...] Read more.

During the past decade, a stem cell-based hypothesis has emerged (among many others) to explain the pathogenesis of endometriosis. The initial hypothesis proposed that endometriosis arose from a single or a few specific cells with stem cell properties, including self-renewal and multi-lineage cell differentiation. The origins of the endometriosis-initiating stem cells were thought to be the bone marrow, uterine endometrium, and other tissues. Based on the implantation or metastatic theory in combination with the initial stem cell theory, one or a few multipotent stem/progenitor cells present in the eutopic endometrium or bone marrow translocate to ectopic sites via fallopian tubes during menstruation, vasculolymphatic routes, or through direct migration and invasion. Subsequently, they give rise to endometriotic lesions followed by differentiation into various cell components of endometriosis, including glandular and stromal cells. Recent somatic mutation analyses of deep infiltrating endometriosis, endometrioma, and eutopic normal endometrium using next-generation sequencing techniques have redefined the stem cell theory. It is now proposed that stem/progenitor cells of at least two different origins—epithelium and stroma—sequentially, differentially, but coordinately contribute to the genesis of endometriosis. The dual stem cell theory on how two (or more) stem/progenitor cells differentially and coordinately participate in the establishment of endometriotic lesions remains to be elucidated. Furthermore, the stem/progenitor cells involved in this theory also remain to be identified. Given that the origin of endometriosis is eutopic endometrium, the candidate cells for endometriotic epithelium-initiating cells are likely to be endometrial epithelial cells positive for either N-cadherin or SSEA-1 or both. The candidate cells for endometriotic stroma-initiating cells may be endometrial mesenchymal stem cells positive for SUSD2. Endometrial side population cells are also a possible candidate because they contain unipotent or multipotent cells capable of behaving as endometrial epithelial and stromal stem/progenitor cells. Full article

(This article belongs to the Special Issue Endometrial Stem/Progenitor Cell Biology: Prospects and Challenges)

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24 pages, 10578 KiB

Open AccessEditor’s ChoiceReview

Ion Channel Involvement in Tumor Drug Resistance

by Concetta Altamura, Paola Gavazzo, Michael Pusch and Jean-François Desaphy

J. Pers. Med. 2022, 12(2), 210; https://doi.org/10.3390/jpm12020210 - 3 Feb 2022

Cited by 18 | Viewed by 3636

Abstract

Over 90% of deaths in cancer patients are attributed to tumor drug resistance. Resistance to therapeutic agents can be due to an innate property of cancer cells or can be acquired during chemotherapy. In recent years, it has become increasingly clear that regulation [...] Read more.

Over 90% of deaths in cancer patients are attributed to tumor drug resistance. Resistance to therapeutic agents can be due to an innate property of cancer cells or can be acquired during chemotherapy. In recent years, it has become increasingly clear that regulation of membrane ion channels is an important mechanism in the development of chemoresistance. Here, we review the contribution of ion channels in drug resistance of various types of cancers, evaluating their potential in clinical management. Several molecular mechanisms have been proposed, including evasion of apoptosis, cell cycle arrest, decreased drug accumulation in cancer cells, and activation of alternative escape pathways such as autophagy. Each of these mechanisms leads to a reduction of the therapeutic efficacy of administered drugs, causing more difficulty in cancer treatment. Thus, targeting ion channels might represent a good option for adjuvant therapies in order to counteract chemoresistance development. Full article

(This article belongs to the Special Issue Ion Channels as Targets of Personalized Medicine)

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20 pages, 1471 KiB

Open AccessEditor’s ChoiceReview

Personalized Dosimetry in Targeted Radiation Therapy: A Look to Methods, Tools and Critical Aspects

by Rachele Danieli, Alessia Milano, Salvatore Gallo, Ivan Veronese, Alessandro Lascialfari, Luca Indovina, Francesca Botta, Mahila Ferrari, Alessandro Cicchetti, Davide Raspanti and Marta Cremonesi

J. Pers. Med. 2022, 12(2), 205; https://doi.org/10.3390/jpm12020205 - 2 Feb 2022

Cited by 19 | Viewed by 4887

Abstract

Targeted radiation therapy (TRT) is a strategy increasingly adopted for the treatment of different types of cancer. The urge for optimization, as stated by the European Council Directive (2013/59/EURATOM), requires the implementation of a personalized dosimetric approach, similar to what already happens in [...] Read more.

Targeted radiation therapy (TRT) is a strategy increasingly adopted for the treatment of different types of cancer. The urge for optimization, as stated by the European Council Directive (2013/59/EURATOM), requires the implementation of a personalized dosimetric approach, similar to what already happens in external beam radiation therapy (EBRT). The purpose of this paper is to provide a thorough introduction to the field of personalized dosimetry in TRT, explaining its rationale in the context of optimization and describing the currently available methodologies. After listing the main therapies currently employed, the clinical workflow for the absorbed dose calculation is described, based on works of the most experienced authors in the literature and recent guidelines. Moreover, the widespread software packages for internal dosimetry are presented and critical aspects discussed. Overall, a selection of the most important and recent articles about this topic is provided. Full article

(This article belongs to the Special Issue The Role of Radiation in Cancer Treatment: New Insights towards Personalized Therapies)

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22 pages, 3565 KiB

Open AccessEditor’s ChoiceReview

Personalized Management of Myocarditis and Inflammatory Cardiomyopathy in Clinical Practice

by Agata Tymińska, Krzysztof Ozierański, Aleksandra Skwarek, Agnieszka Kapłon-Cieślicka, Anna Baritussio, Marcin Grabowski, Renzo Marcolongo and Alida LP Caforio

J. Pers. Med. 2022, 12(2), 183; https://doi.org/10.3390/jpm12020183 - 30 Jan 2022

Cited by 15 | Viewed by 5023

Abstract

Myocarditis is an inflammatory heart disease induced by infectious and non-infectious causes frequently triggering immune-mediated pathologic mechanisms leading to myocardial damage and dysfunction. In approximately half of the patients, acute myocarditis resolves spontaneously while in the remaining cases, it may evolve into serious [...] Read more.

Myocarditis is an inflammatory heart disease induced by infectious and non-infectious causes frequently triggering immune-mediated pathologic mechanisms leading to myocardial damage and dysfunction. In approximately half of the patients, acute myocarditis resolves spontaneously while in the remaining cases, it may evolve into serious complications including inflammatory cardiomyopathy, arrhythmias, death, or heart transplantation. Due to the large variability in clinical presentation, unpredictable course of the disease, and lack of established causative treatment, myocarditis represents a challenging diagnosis in modern cardiology. Moreover, an increase in the incidence of myocarditis and inflammatory cardiomyopathy has been observed in recent years. However, there is a growing potential of available non-invasive diagnostic methods (biomarkers, serum anti-heart autoantibodies (AHA), microRNAs, speckle tracking echocardiography, cardiac magnetic resonance T1 and T2 tissue mapping, positron emission tomography), which may refine the diagnostic workup and/or noninvasive follow-up. Personalized management should include the use of endomyocardial biopsy and AHA, which may allow the etiopathogenetic subsets of myocarditis (infectious, non-infectious, and/or immune-mediated) to be distinguished and implementation of disease-specific therapies. In this review, we summarize current knowledge on myocarditis and inflammatory cardiomyopathy, and outline some practical diagnostic, therapeutic, and follow-up algorithms to facilitate comprehensive individualized management of these patients. Full article

(This article belongs to the Special Issue Personalized Cardiovascular Medicine)

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24 pages, 2124 KiB

Open AccessEditor’s ChoiceReview

Computational Models for Clinical Applications in Personalized Medicine—Guidelines and Recommendations for Data Integration and Model Validation

by Catherine Bjerre Collin, Tom Gebhardt, Martin Golebiewski, Tugce Karaderi, Maximilian Hillemanns, Faiz Muhammad Khan, Ali Salehzadeh-Yazdi, Marc Kirschner, Sylvia Krobitsch, EU-STANDS4PM consortium and Lars Kuepfer

J. Pers. Med. 2022, 12(2), 166; https://doi.org/10.3390/jpm12020166 - 26 Jan 2022

Cited by 38 | Viewed by 10606

Abstract

The future development of personalized medicine depends on a vast exchange of data from different sources, as well as harmonized integrative analysis of large-scale clinical health and sample data. Computational-modelling approaches play a key role in the analysis of the underlying molecular processes [...] Read more.

The future development of personalized medicine depends on a vast exchange of data from different sources, as well as harmonized integrative analysis of large-scale clinical health and sample data. Computational-modelling approaches play a key role in the analysis of the underlying molecular processes and pathways that characterize human biology, but they also lead to a more profound understanding of the mechanisms and factors that drive diseases; hence, they allow personalized treatment strategies that are guided by central clinical questions. However, despite the growing popularity of computational-modelling approaches in different stakeholder communities, there are still many hurdles to overcome for their clinical routine implementation in the future. Especially the integration of heterogeneous data from multiple sources and types are challenging tasks that require clear guidelines that also have to comply with high ethical and legal standards. Here, we discuss the most relevant computational models for personalized medicine in detail that can be considered as best-practice guidelines for application in clinical care. We define specific challenges and provide applicable guidelines and recommendations for study design, data acquisition, and operation as well as for model validation and clinical translation and other research areas. Full article

(This article belongs to the Special Issue Systems Medicine and Bioinformatics)

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15 pages, 992 KiB

Open AccessEditor’s ChoiceReview

Thyroid Diseases and Breast Cancer

by Enke Baldini, Augusto Lauro, Domenico Tripodi, Daniele Pironi, Maria Ida Amabile, Iulia Catalina Ferent, Eleonora Lori, Federica Gagliardi, Maria Irene Bellini, Flavio Forte, Patrizia Pacini, Vito Cantisani, Vito D’Andrea, Salvatore Sorrenti and Salvatore Ulisse

J. Pers. Med. 2022, 12(2), 156; https://doi.org/10.3390/jpm12020156 - 25 Jan 2022

Cited by 16 | Viewed by 6812

Abstract

Epidemiological studies aimed at defining the association of thyroid diseases with extra-thyroidal malignancies (EM) have aroused considerable interest in the possibility of revealing common genetic and environmental factors underlying disease etiology and progression. Over the years, multiple lines of evidence indicated a significant [...] Read more.

Epidemiological studies aimed at defining the association of thyroid diseases with extra-thyroidal malignancies (EM) have aroused considerable interest in the possibility of revealing common genetic and environmental factors underlying disease etiology and progression. Over the years, multiple lines of evidence indicated a significant relationship between thyroid carcinomas and other primary EM, especially breast cancer. For the latter, a prominent association was also found with benign thyroid diseases. In particular, a meta-analysis revealed an increased risk of breast cancer in patients with autoimmune thyroiditis, and our recent work demonstrated that the odds ratio (OR) for breast cancer was raised in both thyroid autoantibody-positive and -negative patients. However, the OR was significantly lower for thyroid autoantibody-positive patients compared to the negative ones. This is in agreement with findings showing that the development of thyroid autoimmunity in cancer patients receiving immunotherapy is associated with better outcome and supports clinical evidence that breast cancer patients with thyroid autoimmunity have longer disease-free interval and overall survival. These results seem to suggest that factors other than oncologic treatments may play a role in the initiation and progression of a second primary malignancy. The molecular links between thyroid autoimmunity and breast cancer remain, however, unidentified, and different hypotheses have been proposed. Here, we will review the epidemiological, clinical, and experimental data relating thyroid diseases and breast cancer, as well as the possible hormonal and molecular mechanisms underlying such associations. Full article

(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Breast Cancer)

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18 pages, 1049 KiB

Open AccessEditor’s ChoiceReview

Adipose-Derived Stem Cells for Facial Rejuvenation

by Agnieszka Surowiecka and Jerzy Strużyna

J. Pers. Med. 2022, 12(1), 117; https://doi.org/10.3390/jpm12010117 - 16 Jan 2022

Cited by 26 | Viewed by 7880

Abstract

The interest in regenerative medicine is increasing, and it is a dynamically developing branch of aesthetic surgery. Biocompatible and autologous-derived products such as platelet-rich plasma or adult mesenchymal stem cells are often used for aesthetic purposes. Their application originates from wound healing and [...] Read more.

The interest in regenerative medicine is increasing, and it is a dynamically developing branch of aesthetic surgery. Biocompatible and autologous-derived products such as platelet-rich plasma or adult mesenchymal stem cells are often used for aesthetic purposes. Their application originates from wound healing and orthopaedics. Adipose-derived stem cells are a powerful agent in skin rejuvenation. They secrete growth factors and anti-inflammatory cytokines, stimulate tissue regeneration by promoting the secretion of extracellular proteins and secrete antioxidants that neutralize free radicals. In an office procedure, without cell incubation and counting, the obtained product is stromal vascular fraction, which consists of not only stem cells but also other numerous active cells such as pericytes, preadipocytes, immune cells, and extra-cellular matrix. Adipose-derived stem cells, when injected into dermis, improved skin density and overall skin appearance, and increased skin hydration and number of capillary vessels. The main limitation of mesenchymal stem cell transfers is the survival of the graft. The final outcomes are dependent on many factors, including the age of the patient, technique of fat tissue harvesting, technique of lipoaspirate preparation, and technique of fat graft injection. It is very difficult to compare available studies because of the differences and multitude of techniques used. Fat harvesting is associated with potentially life-threatening complications, such as massive bleeding, embolism, or clots. However, most of the side effects are mild and transient: primarily hematomas, oedema, and mild pain. Mesenchymal stem cells that do not proliferate when injected into dermis promote neoangiogenesis, that is why respectful caution should be taken in the case of oncologic patients. A longer clinical observation on a higher number of participants should be performed to develop reliable indications and guidelines for transferring ADSCs. Full article

(This article belongs to the Special Issue Adult Stem Cells in Aging)

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28 pages, 2058 KiB

Open AccessEditor’s ChoiceReview

Multi-Omics Profiling Approach to Asthma: An Evolving Paradigm

by Yadu Gautam, Elisabet Johansson and Tesfaye B. Mersha

J. Pers. Med. 2022, 12(1), 66; https://doi.org/10.3390/jpm12010066 - 7 Jan 2022

Cited by 35 | Viewed by 5670

Abstract

Asthma is a complex multifactorial and heterogeneous respiratory disease. Although genetics is a strong risk factor of asthma, external and internal exposures and their interactions with genetic factors also play important roles in the pathophysiology of asthma. Over the past decades, the application [...] Read more.

Asthma is a complex multifactorial and heterogeneous respiratory disease. Although genetics is a strong risk factor of asthma, external and internal exposures and their interactions with genetic factors also play important roles in the pathophysiology of asthma. Over the past decades, the application of high-throughput omics approaches has emerged and been applied to the field of asthma research for screening biomarkers such as genes, transcript, proteins, and metabolites in an unbiased fashion. Leveraging large-scale studies representative of diverse population-based omics data and integrating with clinical data has led to better profiling of asthma risk. Yet, to date, no omic-driven endotypes have been translated into clinical practice and management of asthma. In this article, we provide an overview of the current status of omics studies of asthma, namely, genomics, transcriptomics, epigenomics, proteomics, exposomics, and metabolomics. The current development of the multi-omics integrations of asthma is also briefly discussed. Biomarker discovery following multi-omics profiling could be challenging but useful for better disease phenotyping and endotyping that can translate into advances in asthma management and clinical care, ultimately leading to successful precision medicine approaches. Full article

(This article belongs to the Special Issue Precision Medicine in Childhood Asthma)

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Other

19 pages, 811 KiB

Open AccessEditor’s ChoiceSystematic Review

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

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

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

Cited by 16 | Viewed by 3830

Abstract

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

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

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

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18 pages, 492 KiB

Open AccessEditor’s ChoiceSystematic Review

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

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

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

Cited by 14 | Viewed by 2792

Abstract

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

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

(This article belongs to the Section Mechanisms of Diseases)

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17 pages, 2015 KiB

Open AccessEditor’s ChoiceSystematic Review

The Progress and Pitfalls of Pharmacogenetics-Based Precision Medicine in Schizophrenia Spectrum Disorders: A Systematic Review and Meta-Analysis

by Yuxin Teng, Amrit Sandhu, Edith J. Liemburg, Elnaz Naderi and Behrooz Z. Alizadeh

J. Pers. Med. 2023, 13(3), 471; https://doi.org/10.3390/jpm13030471 - 4 Mar 2023

Cited by 6 | Viewed by 3644

Abstract

The inadequate efficacy and adverse effects of antipsychotics severely affect the recovery of patients with schizophrenia spectrum disorders (SSD). We report the evidence for associations between pharmacogenetic (PGx) variants and antipsychotics outcomes, including antipsychotic response, antipsychotic-induced weight/BMI gain, metabolic syndrome, antipsychotic-related prolactin levels, [...] Read more.

The inadequate efficacy and adverse effects of antipsychotics severely affect the recovery of patients with schizophrenia spectrum disorders (SSD). We report the evidence for associations between pharmacogenetic (PGx) variants and antipsychotics outcomes, including antipsychotic response, antipsychotic-induced weight/BMI gain, metabolic syndrome, antipsychotic-related prolactin levels, antipsychotic-induced tardive dyskinesia (TD), clozapine-induced agranulocytosis (CLA), and drug concentration level (pharmacokinetics) in SSD patients. Through an in-depth systematic search in 2010–2022, we identified 501 records. We included 29 meta-analyses constituting pooled data from 298 original studies over 69 PGx variants across 39 genes, 4 metabolizing phenotypes of CYP2D9, and 3 of CYP2C19. We observed weak unadjusted nominal significant (p < 0.05) additive effects of PGx variants of DRD1, DRD2, DRD3, HTR1A, HTR2A, HTR3A, and COMT (10 variants) on antipsychotic response; DRD2, HTR2C, BDNF, ADRA2A, ADRB3, GNB3, INSIG2, LEP, MC4R, and SNAP25 (14 variants) on weight gain; HTR2C (one variant) on metabolic syndrome; DRD2 (one variant) on prolactin levels; COMT and BDNF (two variants) on TD; HLA-DRB1 (one variant) on CLA; CYP2D6 (four phenotypes) and CYP2C19 (two phenotypes) on antipsychotics plasma levels. In the future, well-designed longitudinal naturalistic multi-center PGx studies are needed to validate the effectiveness of PGx variants in antipsychotic outcomes before establishing any reproducible PGx passport in clinical practice. Full article

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13 pages, 841 KiB

Open AccessEditor’s ChoiceSystematic Review

Does Electrical Stimulation through Nerve Conduits Improve Peripheral Nerve Regeneration?—A Systematic Review

by Sophie Hasiba-Pappas, Lars-P. Kamolz, Hanna Luze, Sebastian P. Nischwitz, Judith C. J. Holzer-Geissler, Alexandru Cristian Tuca, Theresa Rienmüller, Mathias Polz, Daniel Ziesel and Raimund Winter

J. Pers. Med. 2023, 13(3), 414; https://doi.org/10.3390/jpm13030414 - 26 Feb 2023

Cited by 7 | Viewed by 2371

Abstract

Background: Peripheral nerve injuries affect over 2% of trauma patients and can lead to severe functional impairment and permanent disability. Autologous nerve transplantation is still the gold standard in the reconstruction of nerve defects. For small defects, conduits can be considered for bridging. [...] Read more.

Background: Peripheral nerve injuries affect over 2% of trauma patients and can lead to severe functional impairment and permanent disability. Autologous nerve transplantation is still the gold standard in the reconstruction of nerve defects. For small defects, conduits can be considered for bridging. Lately, the combined use of conduits and electrical stimulation has gained attention in the treatment of peripheral nerve injury. This review aimed to present the currently available data on this topic. Methods: PubMed, Embase, Medline and the Cochrane Library were searched for studies on electrical stimulation through nerve conduits for nerve defects in in vivo studies. Results: Fifteen studies fit the inclusion criteria. All of them reported on the application of nerve conduits combined with stimulation for sciatic nerve gaps in rats. Functional, electrophysiological and histological evaluations showed improved nerve regeneration after electrical stimulation. High variation was observed in the treatment protocols. Conclusion: Electrically stimulated conduits could improve peripheral nerve regeneration in rat models. The combined application of nerve guidance conduits and electrical stimulation shows promising results and should be further evaluated under standardized conditions. Full article

(This article belongs to the Special Issue Implications for Personalized Plastic, Aesthetic and Reconstructive Surgery)

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20 pages, 589 KiB

Open AccessEditor’s ChoiceSystematic Review

Menstrual Cycle, Glucose Control and Insulin Sensitivity in Type 1 Diabetes: A Systematic Review

by Elena Gamarra and Pierpaolo Trimboli

J. Pers. Med. 2023, 13(2), 374; https://doi.org/10.3390/jpm13020374 - 20 Feb 2023

Cited by 5 | Viewed by 2602

Abstract

The correlation between the menstrual cycle and glucose control in type 1 diabetes has been the focus of several studies since the 1920s, but a few critical aspects made it particularly challenging to reach conclusive evidence. The aim of this systematic review is [...] Read more.

The correlation between the menstrual cycle and glucose control in type 1 diabetes has been the focus of several studies since the 1920s, but a few critical aspects made it particularly challenging to reach conclusive evidence. The aim of this systematic review is to reveal more solid information about the impact of the menstrual cycle on glycaemic outcomes and insulin sensitivity in type 1 diabetes and highlight the less researched areas. The literature was searched by two authors independently using PubMed/MEDLINE, Embase and Scopus (last search on 2 November 2022). The retrieved data did not allow us to perform a meta-analysis. We included 14 studies published between 1990 and 2022, with sample sizes from 4 to 124 patients. We found a wide heterogeneity in the definition of the menstrual cycle phases, glucose metrics, techniques for determining insulin sensitivity, hormonal assessment and other interfering factors considered, with an overall high risk of bias. There is no conclusive evidence, and published data do not allow us to achieve quantitative results. In a subset of patients, a possible worsening of insulin sensitivity and hyperglycaemia in the luteal phase could be observed. From the clinical standpoint, a cautious strategy based on patient-specific patterns can be considered until new, solid evidence is obtained. Full article

(This article belongs to the Special Issue Hormone Therapies for Women)

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16 pages, 988 KiB

Open AccessEditor’s ChoiceSystematic Review

BMI at Discharge from Treatment Predicts Relapse in Anorexia Nervosa: A Systematic Scoping Review

by Stein Frostad, Natalia Rozakou-Soumalia, Ştefana Dârvariu, Bahareh Foruzesh, Helia Azkia, Malina Ploug Larsen, Ehsan Rowshandel and Jan Magnus Sjögren

J. Pers. Med. 2022, 12(5), 836; https://doi.org/10.3390/jpm12050836 - 20 May 2022

Cited by 17 | Viewed by 5959

Abstract

Background: Anorexia nervosa (AN) has high rates of enduring disease and mortality. Currently, there is insufficient knowledge on the predictors of relapse after weight normalization and this is why a systematic literature review was performed. Methods: PubMed, EMBASE, PsychInfo, and Cochrane databases were [...] Read more.

Background: Anorexia nervosa (AN) has high rates of enduring disease and mortality. Currently, there is insufficient knowledge on the predictors of relapse after weight normalization and this is why a systematic literature review was performed. Methods: PubMed, EMBASE, PsychInfo, and Cochrane databases were searched for literature published until 13 July 2021. All study designs were eligible for inclusion if they focused on predictors of relapse after weight normalization in AN. Individual study definitions of relapse were used, and in general, this was either a drop in BMI and/or reccurrence of AN symptoms. Results: The database search identified 11,507 publications, leaving 9511 publications after the removal of duplicates and after a review of abstracts and titles; 191 were selected for full-text review. Nineteen publications met the criteria and included 1398 AN patients and 39 healthy controls (HC) from adults and adolescents (ages range 11–73 years). The majority used a prospective observational study design (12 studies), a few used a retrospective observational design (6 studies), and only one was a non-randomized control trial (NRCT). Sample sizes ranged from 16 to 191 participants. BMI or measures of body fat and leptin levels at discharge were the strongest predictors of relapse with an approximate relapse rate of 50% at 12 months. Other predictors included signs of eating disorder psychopathology at discharge. Conclusions: BMI at the end of treatment is a predictor of relapse in AN, which is why treatment should target a BMI well above 20. Together with the time to relapse, these outcomes are important to include in the evaluation of current and novel treatments in AN and for benchmarking. Full article

(This article belongs to the Special Issue Biomarkers and Clinical Research in Eating Disorders)

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12 pages, 1056 KiB

Open AccessEditor’s ChoiceSystematic Review

Prevalence of New-Onset Atrial Fibrillation and Associated Outcomes in Patients with Sepsis: A Systematic Review and Meta-Analysis

by Bernadette Corica, Giulio Francesco Romiti, Stefania Basili and Marco Proietti

J. Pers. Med. 2022, 12(4), 547; https://doi.org/10.3390/jpm12040547 - 30 Mar 2022

Cited by 15 | Viewed by 3355

Abstract

Background: New-onset atrial fibrillation (NOAF) is a common complication in patients with sepsis, although its prevalence and impact on outcomes are still unclear. We aim to provide a systematic review and meta-analysis on the prevalence of NOAF in patients with sepsis, and its [...] Read more.

Background: New-onset atrial fibrillation (NOAF) is a common complication in patients with sepsis, although its prevalence and impact on outcomes are still unclear. We aim to provide a systematic review and meta-analysis on the prevalence of NOAF in patients with sepsis, and its impact on in-hospital mortality and intensive care unit (ICU) mortality. Methods: PubMed and EMBASE were systematically searched on 26 December 2021. Studies reporting on the prevalence of NOAF and/or its impact on in-hospital mortality or ICU mortality in patients with sepsis or septic shock were included. The pooled prevalence and 95% confidence intervals (CI) were calculated, as well as the risk ratios (RR), 95%CI and 95% prediction intervals (PI) for outcomes. Subgroup analyses and meta-regressions were performed to account for heterogeneity. Results: Among 4988 records retrieved from the literature search, 22 articles were included. Across 207,847 patients with sepsis, NOAF was found in 13.5% (95%CI: 8.9–20.1%), with high heterogeneity between studies; significant subgroup differences were observed, according to the geographical location, study design and sample size of the included studies. A multivariable meta-regression model showed that sample size and geographical location account for most of the heterogeneity. NOAF patients showed an increased risk of both in-hospital mortality (RR: 1.69, 95%CI: 1.47–1.96, 95%PI: 1.15–2.50) and ICU mortality (RR: 2.12, 95%CI: 1.86–2.43, 95%PI: 1.71–2.63), with moderate to no heterogeneity between the included studies. Conclusions: NOAF is a common complication during sepsis, being present in one out of seven individuals. Patients with NOAF are at a higher risk of adverse events during sepsis, and may need specific therapeutical interventions. Full article

(This article belongs to the Section Epidemiology)

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41 pages, 18497 KiB

Open AccessEditor’s ChoiceSystematic Review

Endoscopic Combined Intrarenal Surgery Versus Percutaneous Nephrolithotomy for Complex Renal Stones: A Systematic Review and Meta-Analysis

by Yung-Hao Liu, Hong-Jie Jhou, Meng-Han Chou, Sheng-Tang Wu, Tai-Lung Cha, Dah-Shyong Yu, Guang-Huan Sun, Po-Huang Chen and En Meng

J. Pers. Med. 2022, 12(4), 532; https://doi.org/10.3390/jpm12040532 - 28 Mar 2022

Cited by 16 | Viewed by 4284

Abstract

Background: Endoscopic combined intrarenal surgery (ECIRS) adds ureteroscopic vision to percutaneous nephrolithotomy (PCNL), which can be helpful when dealing with complex renal stones. Yet, there is still no consensus on the superiority of ECIRS. We aimed to critically analyze the available evidence of [...] Read more.

Background: Endoscopic combined intrarenal surgery (ECIRS) adds ureteroscopic vision to percutaneous nephrolithotomy (PCNL), which can be helpful when dealing with complex renal stones. Yet, there is still no consensus on the superiority of ECIRS. We aimed to critically analyze the available evidence of studies comparing efficacy, safety, bleeding risk, and efficiency of ECIRS and PCNL. Methods: We searched for studies comparing efficacy (initial and final stone-free rate), safety (postoperative fever, overall and severe complications), efficiency (operative time and hospital stay) and bleeding risk between ECIRS and PCNL. Meta-analysis was performed. Results: Seven studies (919 patients) were identified. ECIRS provided a significantly higher initial stone-free rate, higher final stone-free rate, lower overall complications, lower severe complications, and lower rate of requiring blood transfusion. There was no difference between the two groups in terms of postoperative fever, hemoglobin drop, operative time, and hospital stay. In the subgroup analysis, both minimally invasive and conventional ECIRS were associated with a higher stone-free rate and lower complication outcomes. Conclusions: When treating complex renal stones, ECIRS has a better stone-free rate, fewer complications, and requires fewer blood transfusions compared with PCNL. Subgroups either with minimally invasive or conventional intervention showed a consistent trend. Full article

(This article belongs to the Special Issue Postoperative Complications and Personalized Medicine)

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26 pages, 5604 KiB

Open AccessEditor’s ChoiceSystematic Review

The Role of Robotic Visceral Surgery in Patients with Adhesions: A Systematic Review and Meta-Analysis

by Marco Milone, Michele Manigrasso, Pietro Anoldo, Anna D’Amore, Ugo Elmore, Mariano Cesare Giglio, Gianluca Rompianesi, Sara Vertaldi, Roberto Ivan Troisi, Nader K. Francis and Giovanni Domenico De Palma

J. Pers. Med. 2022, 12(2), 307; https://doi.org/10.3390/jpm12020307 - 18 Feb 2022

Cited by 12 | Viewed by 2985

Abstract

Abdominal adhesions are a risk factor for conversion to open surgery. An advantage of robotic surgery is the lower rate of unplanned conversions. A systematic review was conducted using the terms “laparoscopic” and “robotic”. Inclusion criteria were: comparative studies evaluating patients undergoing laparoscopic [...] Read more.

Abdominal adhesions are a risk factor for conversion to open surgery. An advantage of robotic surgery is the lower rate of unplanned conversions. A systematic review was conducted using the terms “laparoscopic” and “robotic”. Inclusion criteria were: comparative studies evaluating patients undergoing laparoscopic and robotic surgery; reporting data on conversion to open surgery for each group due to adhesions and studies including at least five patients in each group. The main outcomes were the conversion rates due to adhesions and surgeons’ expertise (novice vs. expert). The meta-analysis included 70 studies from different surgical specialities with 14,329 procedures (6472 robotic and 7857 laparoscopic). The robotic approach was associated with a reduced risk of conversion (OR 1.53, 95% CI 1.12–2.10, p = 0.007). The analysis of the procedures performed by “expert surgeons” showed a statistically significant difference in favour of robotic surgery (OR 1.48, 95% CI 1.03–2.12, p = 0.03). A reduced conversion rate due to adhesions with the robotic approach was observed in patients undergoing colorectal cancer surgery (OR 2.62, 95% CI 1.20–5.72, p = 0.02). The robotic approach could be a valid option in patients with abdominal adhesions, especially in the subgroup of those undergoing colorectal cancer resection performed by expert surgeons. Full article

(This article belongs to the Special Issue Update on Robotic Gastrointestinal Surgery)

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13 pages, 752 KiB

Open AccessEditor’s ChoiceSystematic Review

The Contribution of “Individual Participant Data” Meta-Analyses of Psychotherapies for Depression to the Development of Personalized Treatments: A Systematic Review

by Pim Cuijpers, Marketa Ciharova, Soledad Quero, Clara Miguel, Ellen Driessen, Mathias Harrer, Marianna Purgato, David Ebert and Eirini Karyotaki

J. Pers. Med. 2022, 12(1), 93; https://doi.org/10.3390/jpm12010093 - 11 Jan 2022

Cited by 31 | Viewed by 4687

Abstract

While randomized trials typically lack sufficient statistical power to identify predictors and moderators of outcome, ”individual participant data” (IPD) meta-analyses, which combine primary data of multiple randomized trials, can increase the statistical power to identify predictors and moderators of outcome. We conducted a [...] Read more.

While randomized trials typically lack sufficient statistical power to identify predictors and moderators of outcome, ”individual participant data” (IPD) meta-analyses, which combine primary data of multiple randomized trials, can increase the statistical power to identify predictors and moderators of outcome. We conducted a systematic review of IPD meta-analyses on psychological treatments of depression to provide an overview of predictors and moderators identified. We included 10 (eight pairwise and two network) IPD meta-analyses. Six meta-analyses showed that higher baseline depression severity was associated with better outcomes, and two found that older age was associated with better outcomes. Because power was high in most IPD meta-analyses, non-significant findings are also of interest because they indicate that these variables are probably not relevant as predictors and moderators. We did not find in any IPD meta-analysis that gender, education level, or relationship status were significant predictors or moderators. This review shows that IPD meta-analyses on psychological treatments can identify predictors and moderators of treatment effects and thereby contribute considerably to the development of personalized treatments of depression. Full article

(This article belongs to the Special Issue Personalized Medicine Approaches to Depression Prevention, Diagnosis, and Therapeutics)

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