Journal of Personalized Medicine

13 pages, 777 KiB

Open AccessEditor’s ChoiceArticle

Myopia Control with Low-Dose Atropine in European Children: Six-Month Results from a Randomized, Double-Masked, Placebo-Controlled, Multicenter Study

by Anders Hvid-Hansen, Nina Jacobsen, Flemming Møller, Toke Bek, Brice Ozenne and Line Kessel

J. Pers. Med. 2023, 13(2), 325; https://doi.org/10.3390/jpm13020325 - 14 Feb 2023

Cited by 5 | Viewed by 2415

Abstract

The effect and safety of low-dose atropine in myopia control have not been studied in randomized, placebo-controlled trials outside Asia. We investigated the efficacy and safety of 0.1% atropine loading dose and 0.01% atropine compared with a placebo in a European population. Investigator-initiated, [...] Read more.

The effect and safety of low-dose atropine in myopia control have not been studied in randomized, placebo-controlled trials outside Asia. We investigated the efficacy and safety of 0.1% atropine loading dose and 0.01% atropine compared with a placebo in a European population. Investigator-initiated, randomized, double-masked, placebo-controlled, equal-allocation, multicenter study comparing 0.1% atropine loading dose (six months) followed by 0.01% atropine (18 months), 0.01% atropine (24 months), and placebo (24 months). Participants were monitored for a 12-months washout period. Outcome measures were axial length (AL), cycloplegic spherical equivalent (SE), photopic and mesopic pupil size, accommodation amplitude, visual acuity, intraocular pressure (IOP), and adverse reactions and events. We randomized 97 participants (mean [standard deviation] age, 9.4 [1.7] years; 55 girls (57%) and 42 boys (43%)). After six months, AL was 0.13 mm shorter (95% confidence interval [CI], −0.18 to −0.07 [adjusted p < 0.001]) with 0.1% atropine loading dose and 0.06 mm shorter (95% CI, −0.11 to −0.01 [adjusted p = 0.06]) with 0.01% atropine than in the placebo group. We observed similar dose-dependent changes in SE, pupil size, accommodation amplitude, and adverse reactions. No significant differences in visual acuity or IOP were found between groups, and no serious adverse reactions were reported. We found a dose-dependent effect of low-dose atropine in European children without adverse reactions requiring photochromatic or progressive spectacles. Our results are comparable to those observed in East Asia, indicating that results on myopia control with low-dose atropine are generalizable across populations with different racial backgrounds. Full article

(This article belongs to the Special Issue Diagnostics and Therapeutics in Ophthalmology)

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15 pages, 4219 KiB

Open AccessEditor’s ChoiceArticle

Advancing Osteoporosis Evaluation Procedures: Detailed Computational Analysis of Regional Structural Vulnerabilities in Osteoporotic Bone

by Matthew A. Wysocki and Scott T. Doyle

J. Pers. Med. 2023, 13(2), 321; https://doi.org/10.3390/jpm13020321 - 13 Feb 2023

Cited by 3 | Viewed by 1500

Abstract

Osteoporotic fractures of the femur are associated with poor healing, disability, reduced quality of life, and high mortality rates within 1 year. Moreover, osteoporotic fractures of the femur are still considered to be an unsolved problem in orthopedic surgery. In order to more [...] Read more.

Osteoporotic fractures of the femur are associated with poor healing, disability, reduced quality of life, and high mortality rates within 1 year. Moreover, osteoporotic fractures of the femur are still considered to be an unsolved problem in orthopedic surgery. In order to more effectively identify osteoporosis-related fracture risk and develop advanced treatment approaches for femur fractures, it is necessary to acquire a greater understanding of how osteoporosis alters the diaphyseal structure and biomechanical characteristics. The current investigation uses computational analyses to comprehensively examine how femur structure and its associated properties differ between healthy and osteoporotic bones. The results indicate statistically significant differences in multiple geometric properties between healthy femurs and osteoporotic femurs. Additionally, localized disparities in the geometric properties are evident. Overall, this approach will be beneficial in the development of new diagnostic procedures for highly detailed patient-specific detection of fracture risk, for establishing novel injury prevention treatments, and for informing advanced surgical solutions. Full article

(This article belongs to the Special Issue Personalized Medicine for Orthopaedic Disorders)

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14 pages, 1069 KiB

Open AccessEditor’s ChoiceArticle

by Eugenio Martelli, Matilde Zamboni, Giovanni Sotgiu, Laura Saderi, Massimo Federici, Giuseppe M. Sangiorgi, Mariangela V. Puci, Allegra R. Martelli, Teresa Messina, Paolo Frigatti, Maria Pia Borrelli, Carlo Ruotolo, Ilaria Ficarelli, Paolo Rubino, Francesco Pezzo, Luciano Carbonari, Andrea Angelini, Edoardo Galeazzi, Luca Calia Di Pinto, Franco M. Fiore, Armando Palmieri, Giorgio Ventoruzzo, Giulia Mazzitelli, Franco Ragni, Antonio Bozzani, Enzo Forliti, Claudio Castagno, Pietro Volpe, Mafalda Massara, Diego Moniaci, Elisa Pagliasso, Tania Peretti, Mauro Ferrari, Nicola Troisi, Piero Modugno, Maurizio Maiorano, Umberto M. Bracale, Marco Panagrosso, Mario Monaco, Giovanni Giordano, Giuseppe Natalicchio, Antonella Biello, Giovanni M. Celoria, Alessio Amico, Mauro Di Bartolo, Massimiliano Martelli, Roberta Munaó, Davide Razzano, Giovanni Colacchio, Francesco Bussetti, Gaetano Lanza, Antonio Cardini, Bartolomeo Di Benedetto, Mario De Laurentis, Maurizio Taurino, Pasqualino Sirignano, Pierluigi Cappiello, Andrea Esposito, Santi Trimarchi, Silvia Romagnoli, Andrea Padricelli, Giorgio Giudice, Adolfo Crinisio, Giovanni Di Nardo, Giuseppe Battaglia, Rosario Tringale, Salvatore De Vivo, Rita Compagna, Valerio S. Tolva, Ilenia D’Alessio, Ruggiero Curci, Simona Giovannetti, Giuseppe D’Arrigo, Giusi Basile, Dalmazio Frigerio, Gian Franco Veraldi, Luca Mezzetto, Arnaldo Ippoliti, Fabio M. Oddi and Alberto M. Settembrini Show full author list Hide full author list

J. Pers. Med. 2023, 13(2), 316; https://doi.org/10.3390/jpm13020316 - 11 Feb 2023

Cited by 8 | Viewed by 1570

Abstract

Background: Identifying sex-related differences/variables associated with 30 day/1 year mortality in patients with chronic limb-threatening ischemia (CLTI). Methods: Multicenter/retrospective/observational study. A database was sent to all the Italian vascular surgeries to collect all the patients operated on for CLTI in 2019. Acute lower-limb [...] Read more.

Background: Identifying sex-related differences/variables associated with 30 day/1 year mortality in patients with chronic limb-threatening ischemia (CLTI). Methods: Multicenter/retrospective/observational study. A database was sent to all the Italian vascular surgeries to collect all the patients operated on for CLTI in 2019. Acute lower-limb ischemia and neuropathic-diabetic foot are not included. Follow-up: One year. Data on demographics/comorbidities, treatments/outcomes, and 30 day/1 year mortality were investigated. Results: Information on 2399 cases (69.8% men) from 36/143 (25.2%) centers. Median (IQR) age: 73 (66–80) and 79 (71–85) years for men/women, respectively (p < 0.0001). Women were more likely to be over 75 (63.2% vs. 40.1%, p = 0.0001). More men smokers (73.7% vs. 42.2%, p < 0.0001), are on hemodialysis (10.1% vs. 6.7%, p = 0.006), affected by diabetes (61.9% vs. 52.8%, p < 0.0001), dyslipidemia (69.3% vs. 61.3%, p < 0.0001), hypertension (91.8% vs. 88.5%, p = 0.011), coronaropathy (43.9% vs. 29.4%, p < 0.0001), bronchopneumopathy (37.1% vs. 25.6%, p < 0.0001), underwent more open/hybrid surgeries (37.9% vs. 28.8%, p < 0.0001), and minor amputations (22% vs. 13.7%, p < 0.0001). More women underwent endovascular revascularizations (61.6% vs. 55.2%, p = 0.004), major amputations (9.6% vs. 6.9%, p = 0.024), and obtained limb-salvage if with limited gangrene (50.8% vs. 44.9%, p = 0.017). Age > 75 (HR = 3.63, p = 0.003) is associated with 30 day mortality. Age > 75 (HR = 2.14, p < 0.0001), nephropathy (HR = 1.54, p < 0.0001), coronaropathy (HR = 1.26, p = 0.036), and infection/necrosis of the foot (dry, HR = 1.42, p = 0.040; wet, HR = 2.04, p < 0.0001) are associated with 1 year mortality. No sex-linked difference in mortality statistics. Conclusion: Women exhibit fewer comorbidities but are struck by CLTI when over 75, a factor associated with short- and mid-term mortality, explaining why mortality does not statistically differ between the sexes. Full article

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40 pages, 1012 KiB

Open AccessEditor’s ChoiceReview

Systemic Cytokines in Retinopathy of Prematurity

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

J. Pers. Med. 2023, 13(2), 291; https://doi.org/10.3390/jpm13020291 - 05 Feb 2023

Cited by 6 | Viewed by 2301

Abstract

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

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

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

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23 pages, 843 KiB

Open AccessEditor’s ChoiceReview

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

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

J. Pers. Med. 2023, 13(2), 286; https://doi.org/10.3390/jpm13020286 - 03 Feb 2023

Cited by 6 | Viewed by 6630

Abstract

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

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

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

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17 pages, 1736 KiB

Open AccessEditor’s ChoiceReview

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

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

J. Pers. Med. 2023, 13(2), 284; https://doi.org/10.3390/jpm13020284 - 02 Feb 2023

Cited by 6 | Viewed by 4428

Abstract

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

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

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

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13 pages, 2265 KiB

Open AccessEditor’s ChoiceSystematic Review

Effectiveness of Hyperthermic Intraperitoneal Chemotherapy Associated with Cytoreductive Surgery in the Treatment of Advanced Ovarian Cancer: Systematic Review and Meta-Analysis

by Maria Llueca, Maria Victoria Ibañez, Maria Teresa Climent, Anna Serra and Antoni Llueca

J. Pers. Med. 2023, 13(2), 258; https://doi.org/10.3390/jpm13020258 - 30 Jan 2023

Cited by 3 | Viewed by 1376

Abstract

Objective: The use of hyperthermic intraperitoneal chemotherapy (HIPEC) as a treatment for epithelial ovarian cancer remains controversial. Our study aims to analyze the overall survival and disease-free survival for the use of HIPEC as a treatment for advanced epithelial ovarian cancer after neoadjuvant [...] Read more.

Objective: The use of hyperthermic intraperitoneal chemotherapy (HIPEC) as a treatment for epithelial ovarian cancer remains controversial. Our study aims to analyze the overall survival and disease-free survival for the use of HIPEC as a treatment for advanced epithelial ovarian cancer after neoadjuvant chemotherapy. Methods: A systematic review and meta-analysis was carried out using PubMed, Cochrane, Web of Science, and ClinicalTrials.gov. A total of six studies were used, comprising a total of 674 patients. Results: The results of our meta-analysis of all studies analyzed together (observational and randomized controlled trials (RCT)) did not achieve significant results. Contrary to the OS (HR = 0.56, 95% IC = 0.33–0.95, p = 0.03) and DFS (HR = 0.61, 95% IC = 0.43–0.86, p < 0.01) of the RCT analyzed separately, a clear impact on survival was suggested. The subgroup analysis showed that studies making use of higher temperatures (≥42 °C) for a shorter period of time (≤60 min) achieved better results for both OS and DFS, as well as the use of cisplatin as the form of chemotherapy in HIPEC. Moreover, the use of HIPEC did not increase high-grade complications. Conclusions: The addition of HIPEC to cytoreductive surgery demonstrates an improvement in OS and DFS for patients with epithelial ovarian cancer in advanced stages, without an increase in the number of complications. The use of cisplatin as chemotherapy in HIPEC obtained better results. Full article

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28 pages, 961 KiB

Open AccessEditor’s ChoiceReview

The Rationale for Vitamin, Mineral, and Cofactor Treatment in the Precision Medical Care of Autism Spectrum Disorder

by Neluwa-Liyanage R. Indika, Richard E. Frye, Daniel A. Rossignol, Susan C. Owens, Udara D. Senarathne, Andreas M. Grabrucker, Rasika Perera, Marielle P. K. J. Engelen and Nicolaas E. P. Deutz

J. Pers. Med. 2023, 13(2), 252; https://doi.org/10.3390/jpm13020252 - 29 Jan 2023

Cited by 12 | Viewed by 7515

Abstract

Children with autism spectrum disorder may exhibit nutritional deficiencies due to reduced intake, genetic variants, autoantibodies interfering with vitamin transport, and the accumulation of toxic compounds that consume vitamins. Importantly, vitamins and metal ions are essential for several metabolic pathways and for neurotransmitter [...] Read more.

Children with autism spectrum disorder may exhibit nutritional deficiencies due to reduced intake, genetic variants, autoantibodies interfering with vitamin transport, and the accumulation of toxic compounds that consume vitamins. Importantly, vitamins and metal ions are essential for several metabolic pathways and for neurotransmitter functioning. The therapeutic benefits of supplementing vitamins, minerals (Zinc, Magnesium, Molybdenum, and Selenium), and other cofactors (coenzyme Q10, alpha-lipoic acid, and tetrahydrobiopterin) are mediated through their cofactor as well as non-cofactor functions. Interestingly, some vitamins can be safely administered at levels far above the dose typically used to correct the deficiency and exert effects beyond their functional role as enzyme cofactors. Moreover, the interrelationships between these nutrients can be leveraged to obtain synergistic effects using combinations. The present review discusses the current evidence for using vitamins, minerals, and cofactors in autism spectrum disorder, the rationale behind their use, and the prospects for future use. Full article

(This article belongs to the Section Mechanisms of Diseases)

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16 pages, 3239 KiB

Open AccessEditor’s ChoiceSystematic Review

Robotic Surgery and Functional Esophageal Disorders: A Systematic Review and Meta-Analysis

by Sara Vertaldi, Anna D’Amore, Michele Manigrasso, Pietro Anoldo, Alessia Chini, Francesco Maione, Marcella Pesce, Giovanni Sarnelli, Giovanni Domenico De Palma and Marco Milone

J. Pers. Med. 2023, 13(2), 231; https://doi.org/10.3390/jpm13020231 - 27 Jan 2023

Cited by 3 | Viewed by 1187

Abstract

The functional disease of the esophago-gastric junction (EGJ) is one of the most common health problems. It often happens that patients suffering from GERD need surgical management. The laparoscopic fundoplication has been considered the gold standard surgical treatment for functional diseases of the [...] Read more.

The functional disease of the esophago-gastric junction (EGJ) is one of the most common health problems. It often happens that patients suffering from GERD need surgical management. The laparoscopic fundoplication has been considered the gold standard surgical treatment for functional diseases of the EGJ. The aim of our meta-analysis is to investigate functional outcomes after robotic fundoplication compared with conventional laparoscopic fundoplication. A prospective search of online databases was performed by two independent reviewers using the search string “robotic and laparoscopic fundoplication”, including all the articles from 1996 to December 2021. The risk of bias within each study was assessed with the Cochrane ROBINS-I and RoB 2.0 tools. Statistical analysis was performed using Review Manager version 5.4. In addition, sixteen studies were included in the final analysis, involving only four RCTs. The primary endpoints were functional outcomes after laparoscopic (LF) and robotic fundoplication (RF). No significant differences between the two groups were found in 30-day readmission rates (p = 0.73), persistence of symptomatology at follow-up (p = 0.60), recurrence (p = 0.36), and reoperation (p = 0.81). The laparoscopic fundoplication represents the gold standard treatment for the functional disease of the EGJ. According to our results, the robotic approach seems to be safe and feasible as well. Further randomized controlled studies are required to better evaluate the advantages of robotic fundoplication. Full article

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

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17 pages, 579 KiB

Open AccessEditor’s ChoiceReview

Radiomics in Lung Metastases: A Systematic Review

by Michela Gabelloni, Lorenzo Faggioni, Roberta Fusco, Igino Simonetti, Federica De Muzio, Giuliana Giacobbe, Alessandra Borgheresi, Federico Bruno, Diletta Cozzi, Francesca Grassi, Mariano Scaglione, Andrea Giovagnoni, Antonio Barile, Vittorio Miele, Nicoletta Gandolfo and Vincenza Granata

J. Pers. Med. 2023, 13(2), 225; https://doi.org/10.3390/jpm13020225 - 27 Jan 2023

Cited by 6 | Viewed by 2163

Abstract

Due to the rich vascularization and lymphatic drainage of the pulmonary tissue, lung metastases (LM) are not uncommon in patients with cancer. Radiomics is an active research field aimed at the extraction of quantitative data from diagnostic images, which can serve as useful [...] Read more.

Due to the rich vascularization and lymphatic drainage of the pulmonary tissue, lung metastases (LM) are not uncommon in patients with cancer. Radiomics is an active research field aimed at the extraction of quantitative data from diagnostic images, which can serve as useful imaging biomarkers for a more effective, personalized patient care. Our purpose is to illustrate the current applications, strengths and weaknesses of radiomics for lesion characterization, treatment planning and prognostic assessment in patients with LM, based on a systematic review of the literature. Full article

(This article belongs to the Special Issue Imaging Biomarkers in Oncology)

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15 pages, 18093 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 8 | Viewed by 1789

Abstract

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

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

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

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14 pages, 7413 KiB

Open AccessEditor’s ChoiceArticle

Functional Alignment Philosophy in Total Knee Arthroplasty—Rationale and Technique for the Valgus Morphotype Using an Image Based Robotic Platform and Individualized Planning

by Jobe Shatrov, Constant Foissey, Moussa Kafelov, Cécile Batailler, Stanislas Gunst, Elvire Servien and Sébastien Lustig

J. Pers. Med. 2023, 13(2), 212; https://doi.org/10.3390/jpm13020212 - 26 Jan 2023

Cited by 4 | Viewed by 4611

Abstract

Functional alignment (FA) is a novel philosophy to deliver a total knee arthroplasty (TKA) that respects individual bony and soft tissue phenotypes within defined limitations. The purpose of this paper is to describe the rationale and technique of FA in the valgus morphotype [...] Read more.

Functional alignment (FA) is a novel philosophy to deliver a total knee arthroplasty (TKA) that respects individual bony and soft tissue phenotypes within defined limitations. The purpose of this paper is to describe the rationale and technique of FA in the valgus morphotype with the use of an image-based robotic-platform. For the valgus phenotype the principles are personalized pre-operative planning, reconstitution of native coronal alignment without residual varus or valgus of more than 3°, restoration of dynamic sagittal alignment within 5° of neutral, implant sizing to match anatomy, and achievement of defined soft tissue laxity in extension and flexion through implant manipulation within the defined boundaries. An individualized plan is created from pre-operative imaging. Next, a reproducible and quantifiable assessment of soft tissue laxity is performed in extension and flexion. Implant positioning is then manipulated in all three planes if necessary to achieve target gap measurements and a final limb position within a defined coronal and sagittal range. FA is a novel TKA technique that aims to restore constitutional bony alignment and balance the laxity of the soft tissues by placing and sizing implants in a manner that respects variations in individual anatomy and soft tissues within defined limits. Full article

(This article belongs to the Special Issue Latest Advances in Musculoskeletal (Orthopedic) Surgery)

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16 pages, 662 KiB

Open AccessEditor’s ChoiceReview

How Wearable Sensors Can Support the Research on Foetal and Pregnancy Outcomes: A Scoping Review

by Andrea Maugeri, Martina Barchitta and Antonella Agodi

J. Pers. Med. 2023, 13(2), 218; https://doi.org/10.3390/jpm13020218 - 26 Jan 2023

Cited by 4 | Viewed by 2041

Abstract

The application of innovative technologies, and in particular of wearable devices, can potentially transform the field of antenatal care with the aim of improving maternal and new-born health through a personalized approach. The present study undertakes a scoping review to systematically map the [...] Read more.

The application of innovative technologies, and in particular of wearable devices, can potentially transform the field of antenatal care with the aim of improving maternal and new-born health through a personalized approach. The present study undertakes a scoping review to systematically map the literature about the use wearable sensors in the research of foetal and pregnancy outcomes. Online databases were used to identify papers published between 2000–2022, from which we selected 30 studies: 9 on foetal outcomes and 21 on maternal outcomes. Included studies focused primarily on the use of wearable devices for monitoring foetal vital signs (e.g., foetal heart rate and movements) and maternal activity during pregnancy (e.g., sleep patterns and physical activity levels). There were many studies that focused on development and/or validation of wearable devices, even if often they included a limited number of pregnant women without pregnancy complications. Although their findings support the potential adoption of wearable devices for both antenatal care and research, there is still insufficient evidence to design effective interventions. Therefore, high quality research is needed to determine which and how wearable devices could support antenatal care. Full article

(This article belongs to the Special Issue Precision Medicine for Epidemiology and Public Health)

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18 pages, 2116 KiB

Open AccessEditor’s ChoiceArticle

Differences and Similarities in Empathy Deficit and Its Neural Basis between Logopenic and Amnesic Alzheimer’s Disease

by Giulia Giacomucci, Cristina Polito, Valentina Berti, Sonia Padiglioni, Giulia Galdo, Salvatore Mazzeo, Enrico Bergamin, Valentina Moschini, Carmen Morinelli, Claudia Nuti, Maria Teresa De Cristofaro, Assunta Ingannato, Silvia Bagnoli, Benedetta Nacmias, Sandro Sorbi and Valentina Bessi

J. Pers. Med. 2023, 13(2), 208; https://doi.org/10.3390/jpm13020208 - 25 Jan 2023

Cited by 3 | Viewed by 1590

Abstract

The aims of the study were to assess empathy deficit and neuronal correlates in logopenic primary progressive aphasia (lv-PPA) and compare these data with those deriving from amnesic Alzheimer’s disease (AD). Eighteen lv-PPA and thirty-eight amnesic AD patients were included. Empathy in both [...] Read more.

The aims of the study were to assess empathy deficit and neuronal correlates in logopenic primary progressive aphasia (lv-PPA) and compare these data with those deriving from amnesic Alzheimer’s disease (AD). Eighteen lv-PPA and thirty-eight amnesic AD patients were included. Empathy in both cognitive and affective domains was assessed by Informer-rated Interpersonal Reactivity Index (perspective taking, PT, and fantasy, FT, for cognitive empathy; empathic concern, EC, and personal distress, PD, for affective empathy) before (T0) and after (T1) cognitive symptoms’ onset. Emotion recognition was explored through the Ekman 60 Faces Test. Cerebral FDG-PET was used to explore neural correlates underlying empathy deficits. From T0 to T1, PT scores decreased, and PD scores increased in both lv-PPA (PT z = −3.43, p = 0.001; PD z = −3.62, p < 0.001) and in amnesic AD (PT z = −4.57, p < 0.001; PD z = −5.20, p < 0.001). Delta PT (T0–T1) negatively correlated with metabolic disfunction of the right superior temporal gyrus, fusiform gyrus, and middle frontal gyrus (MFG) in amnesic AD and of the left inferior parietal lobule (IPL), insula, MFG, and bilateral superior frontal gyrus (SFG) in lv-PPA (p < 0.005). Delta PD (T0-T1) positively correlated with metabolic disfunction of the right inferior frontal gyrus in amnesic AD (p < 0.001) and of the left IPL, insula, and bilateral SFG in lv-PPA (p < 0.005). Lv-PPA and amnesic AD share the same empathic changes, with a damage of cognitive empathy and a heightening of personal distress over time. The differences in metabolic disfunctions correlated with empathy deficits might be due to a different vulnerability of specific brain regions in the two AD clinical presentations. Full article

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

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14 pages, 289 KiB

Open AccessEditor’s ChoiceArticle

Contribution to the Personalized Management of the Nosocomial Infections: A New Paradigm Regarding the Influence of the Community Microbial Environment on the Incidence of the Healthcare-Associated Infections (HAI) in Emergency Hospital Surgical Departments

by Maria-Cristina Mateescu, Simona Grigorescu, Bogdan Socea, Vlad Bloanca and Ovidiu-Dan Grigorescu

J. Pers. Med. 2023, 13(2), 210; https://doi.org/10.3390/jpm13020210 - 25 Jan 2023

Cited by 6 | Viewed by 1658

Abstract

Background: The management of acute surgical pathology implies not only the diagnosis–treatment sequence but also an important preventive component. In the surgical hospital department, wound infection is one of the most frequent complications which must be managed both in a preventive and a [...] Read more.

Background: The management of acute surgical pathology implies not only the diagnosis–treatment sequence but also an important preventive component. In the surgical hospital department, wound infection is one of the most frequent complications which must be managed both in a preventive and a personalized manner. To achieve this goal, several factors of negative local evolution, contributing to the slowdown of the healing processes, such as the colonization and contamination of the wounds, need to be emphasized and controlled from the first moment. In this context, knowing the bacteriological status at admission ensures the distinction between the colonization and infection processes and could help to manage in an efficient way the fight against bacterial pathogen infections from the beginning. Methods: A prospective study was performed for 21 months on 973 patients hospitalized as emergencies in the Plastic and Reconstructive Surgery Department within the Emergency University County Hospital of Brasov, Romania. We analyzed the bacteriological profile of the patients from admission to discharge and the bidirectional and cyclic microorganism dynamics both in the hospital and the community microbial environment. Results: Of the 973 samples collected at admission, 702 were positive, with 17 bacterial species and one fungal, with a predominance of Gram-positive cocci at 74,85%. The most frequently isolated strains were Staphylococcus species (86.51% of the Gram-positive/64.7% of the total isolated strains), while Klebsiella at 8.16% and Pseudomonas aeruginosa species at 5.63% were mainly emphasized in the case of Gram-negative bacilli. Two to seven pathogens were introduced after admission, suggesting that the community microbial environment is in a process of evolution and enrichment with hospital pathogens. Conclusions: The high level of positive bacteriological samples and the complex associations of the pathogens found at the admission bacteriological screening sustain the new idea that the pathogenic microorganisms existing in the community microbial environment have started to increasingly influence the hospital microbial environment, in contrast with the previous consideration, which emphasized only the unidirectional relationship between hospital infections and the changing bacteriological characteristics of the community environment. This modified paradigm must become the basis of a new personalized approach to the management of nosocomial infections. Full article

14 pages, 602 KiB

Open AccessEditor’s ChoiceReview

Management of Irreparable Posterosuperior Rotator Cuff Tears—A Current Concepts Review and Proposed Treatment Algorithm by the AGA Shoulder Committee

by Jonas Pogorzelski, Marco-Christopher Rupp, Bastian Scheiderer, Lucca Lacheta, Benedikt Schliemann, Jakob Schanda, Philipp Heuberer, Marco Schneider, Michael Hackl, AGA Shoulder Committee—Rotator Cuff and Olaf Lorbach

J. Pers. Med. 2023, 13(2), 191; https://doi.org/10.3390/jpm13020191 - 21 Jan 2023

Cited by 4 | Viewed by 2709

Abstract

Posterosuperior rotator cuff tears range among the most common causes of shoulder complaints. While non-operative treatment is typically reserved for the elderly patient with low functional demands, surgical treatment is considered the gold standard for active patients. More precisely, an anatomic rotator cuff [...] Read more.

Posterosuperior rotator cuff tears range among the most common causes of shoulder complaints. While non-operative treatment is typically reserved for the elderly patient with low functional demands, surgical treatment is considered the gold standard for active patients. More precisely, an anatomic rotator cuff repair (RCR) is considered the most desirable treatment option and should be generally attempted during surgery. If an anatomic RCR is impossible, the adequate choice of treatment for irreparable rotator cuff tears remains a matter of debate among shoulder surgeons. Following a critical review of the contemporary literature, the authors suggest the following evidence- and experience-based treatment recommendation. In the non-functional, osteoarthritic shoulder, treatment strategies in the management of irreparable posterosuperior RCT include debridement-based procedures and reverse total shoulder arthroplasty as the treatment of choice. Joint-preserving procedures aimed at restoring glenohumeral biomechanics and function should be reserved for the non-osteoarthritic shoulder. Prior to these procedures, however, patients should be counseled about deteriorating results over time. Recent innovations such as the superior capsule reconstruction and the implantation of a subacromial spacer show promising short-term results, yet future studies with long-term follow-up are required to derive stronger recommendations. Full article

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

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13 pages, 1884 KiB

Open AccessEditor’s ChoiceArticle

Learning Curve of Robotic Lobectomy for the Treatment of Lung Cancer: How Does It Impact on the Autonomic Nervous System of the Surgeon?

by Antonio Mazzella, Shehab Mohamed, Patrick Maisonneuve, Giulia Sedda, Andrea Cara, Monica Casiraghi, Francesco Petrella, Stefano Maria Donghi, Giorgio Lo Iacono and Lorenzo Spaggiari

J. Pers. Med. 2023, 13(2), 193; https://doi.org/10.3390/jpm13020193 - 21 Jan 2023

Cited by 3 | Viewed by 1585

Abstract

Objective: Our purpose is to define the learning curve for robot-assisted thoracoscopic surgery lobectomy by reporting the experience of a single surgeon. Material and methods: We progressively collected the data concerning the surgical performance of a single male thoracic surgeon, from the beginning [...] Read more.

Objective: Our purpose is to define the learning curve for robot-assisted thoracoscopic surgery lobectomy by reporting the experience of a single surgeon. Material and methods: We progressively collected the data concerning the surgical performance of a single male thoracic surgeon, from the beginning of his robotic activity as first operator from January 2021 to June 2022. We evaluated several pre-, intra- and postoperative parameters concerning patients and intraoperative cardiovascular and respiratory outcomes of the surgeon, recorded during surgical interventions, in order to evaluate his cardiovascular stress. We used cumulative sum control charts (CUSUM) to analyze the learning curve. Results: A total of 72 lung lobectomies were performed by a single surgeon in this period. Analyzing the CUSUM of several parameters, the inflection point identifying the transition beyond the surgeon learning phase was reached at cases 28, 22, 27 and 33 when considering operating time, mean heart rate, max heart rate and mean respiratory rate, respectively. Conclusions: The learning curve for robotic lobectomy seems to be safe and feasible with a correct robotic training program. The analysis of a single surgeon from the beginning of his robotic activity demonstrates that confidence, competence, dexterity and security are achieved after about 20–30 procedures, without compromising efficiency and oncological radicality. Full article

(This article belongs to the Special Issue Innovative Approaches in Lung Cancer Treatment)

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17 pages, 1715 KiB

Open AccessEditor’s ChoiceArticle

Multi-Objective Genetic Algorithm for Cluster Analysis of Single-Cell Transcriptomes

by Konghao Zhao, Jason M. Grayson and Natalia Khuri

J. Pers. Med. 2023, 13(2), 183; https://doi.org/10.3390/jpm13020183 - 20 Jan 2023

Cited by 3 | Viewed by 2435

Abstract

Cells are the basic building blocks of human organisms, and the identification of their types and states in transcriptomic data is an important and challenging task. Many of the existing approaches to cell-type prediction are based on clustering methods that optimize only one [...] Read more.

Cells are the basic building blocks of human organisms, and the identification of their types and states in transcriptomic data is an important and challenging task. Many of the existing approaches to cell-type prediction are based on clustering methods that optimize only one criterion. In this paper, a multi-objective Genetic Algorithm for cluster analysis is proposed, implemented, and systematically validated on 48 experimental and 60 synthetic datasets. The results demonstrate that the performance and the accuracy of the proposed algorithm are reproducible, stable, and better than those of single-objective clustering methods. Computational run times of multi-objective clustering of large datasets were studied and used in supervised machine learning to accurately predict the execution times of clustering of new single-cell transcriptomes. Full article

(This article belongs to the Special Issue Development and Application of Bioinformatics in Personalized Medicine)

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26 pages, 962 KiB

Open AccessEditor’s ChoiceReview

The Effect of Interventions on Preventing Musculoskeletal Injuries Related to Nurses Work: Systematic Review

by Armando David Sousa, Cristina Lavareda Baixinho, Maria Helena Presado and Maria Adriana Henriques

J. Pers. Med. 2023, 13(2), 185; https://doi.org/10.3390/jpm13020185 - 20 Jan 2023

Cited by 4 | Viewed by 3934

Abstract

Background: The 12-month prevalence of musculoskeletal disorders related to work (MDRW) in nurses rests between 71.8% to 84%, so it is urgent to develop preventive intervention programs with the purpose of avoiding negative physical, psychological, socioeconomic, and working aspects. There are several intervention [...] Read more.

Background: The 12-month prevalence of musculoskeletal disorders related to work (MDRW) in nurses rests between 71.8% to 84%, so it is urgent to develop preventive intervention programs with the purpose of avoiding negative physical, psychological, socioeconomic, and working aspects. There are several intervention programs aimed at preventing musculoskeletal disorders related to work for nurses, but few have successfully proven results. Despite the evidence pointing to the benefits of multidimensional intervention programs, it is essential to determine which interventions have positive effects on the prevention of this kind of disorder to create an effective intervention plan. Aim: This review intends to identify the different interventions adopted in the prevention of musculoskeletal disorders related to work in nurses and to compare the effectiveness of these interventions, providing the appropriate and scientific basis for building an intervention to prevent musculoskeletal disorders in nurses. Method: This Systematic Review was guided by the research question, “What are the effects of musculoskeletal disorders preventive interventions on nursing practice?” and carried out in different databases (MEDLINE, CINAHL, and Cochrane Central Register of Controlled Trials, SCOPUS, and Science Direct). Later, the results were submitted to the eligibility criteria, the appraisal quality of the papers, and the data synthesis was performed. Results: 13 articles were identified for analysis. The interventions implemented to control the risk were: training patient-handling devices; ergonomics education; involving the management chain; handling protocol/algorithms; acquiring ergonomics equipment; and no-manual lifting. Conclusions: The studies associated two or more interventions, the majority of which (11 studies) were training-handling devices and ergonomics education, therefore emerging as the most effective instruments in the prevention of MDRW. The studies did not associate interventions that cover all risk factors (individual, associated with the nature of the work, organizational, and psychological aspects). This systematic review can help with making recommendations for other studies that should associate organizational measures and prevention policies with physical exercise and other measures aimed at individual and psychosocial risk factors. Full article

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

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17 pages, 1316 KiB

Open AccessEditor’s ChoiceReview

Updated Views in Targeted Therapy in the Patient with Non-Small Cell Lung Cancer

by Miguel A. Ortega, Leonel Pekarek, Fátima Navarro, Oscar Fraile-Martínez, Cielo García-Montero, Miguel Ángel Álvarez-Mon, Raúl Diez-Pedrero, María del Carmen Boyano-Adánez, Luis G. Guijarro, Silvestra Barrena-Blázquez, Ana M. Gómez-Lahoz, Sergio Haro, Mónica Arroyo, Jorge Monserrat, Miguel A. Saez and Melchor Alvarez-Mon

J. Pers. Med. 2023, 13(2), 167; https://doi.org/10.3390/jpm13020167 - 17 Jan 2023

Cited by 6 | Viewed by 2459

Abstract

Non-small cell lung cancer (NSCLC) is the most frequent form of lung cancer and represents a set of histological entities that have an ominous long-term prognosis, for example, adenocarcinoma, squamous carcinoma and large cell carcinoma. Both small cell and non-small cell lung cancer [...] Read more.

Non-small cell lung cancer (NSCLC) is the most frequent form of lung cancer and represents a set of histological entities that have an ominous long-term prognosis, for example, adenocarcinoma, squamous carcinoma and large cell carcinoma. Both small cell and non-small cell lung cancer are the main causes of oncological death and the oncological diseases with the highest incidence worldwide. With regard to clinical approaches for NSCLC, several advances have been achieved in diagnosis and treatment; the analysis of different molecular markers has led to the development of new targeted therapies that have improved the prognosis for selected patients. Despite this, most patients are diagnosed in an advanced stage, presenting a limited life expectancy with an ominous short-term prognosis. Numerous molecular alterations have been described in recent years, allowing for the development of therapies directed against specific therapeutic targets. The correct identification of the expression of different molecular markers has allowed for the individualization of treatment throughout the disease course, expanding the available therapeutic arsenal. The purpose of this article is to summarize the main characteristics of NSCLC and the advances that have occurred in the use of targeted therapies, thus explaining the limitations that have been observed in the management of this disease. Full article

(This article belongs to the Special Issue Immune-Mediated Diseases)

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12 pages, 5291 KiB

Open AccessEditor’s ChoiceArticle

A Deep Learning Method for Quantification of Femoral Head Necrosis Based on Routine Hip MRI for Improved Surgical Decision Making

by Adrian C. Ruckli, Andreas K. Nanavati, Malin K. Meier, Till D. Lerch, Simon D. Steppacher, Sébastian Vuilleumier, Adam Boschung, Nicolas Vuillemin, Moritz Tannast, Klaus A. Siebenrock, Nicolas Gerber and Florian Schmaranzer

J. Pers. Med. 2023, 13(1), 153; https://doi.org/10.3390/jpm13010153 - 12 Jan 2023

Cited by 3 | Viewed by 2703

Abstract

(1) Background: To evaluate the performance of a deep learning model to automatically segment femoral head necrosis (FHN) based on a standard 2D MRI sequence compared to manual segmentations for 3D quantification of FHN. (2) Methods: Twenty-six patients (thirty hips) with [...] Read more.

(1) Background: To evaluate the performance of a deep learning model to automatically segment femoral head necrosis (FHN) based on a standard 2D MRI sequence compared to manual segmentations for 3D quantification of FHN. (2) Methods: Twenty-six patients (thirty hips) with avascular necrosis underwent preoperative MR arthrography including a coronal 2D PD-w sequence and a 3D T1 VIBE sequence. Manual ground truth segmentations of the necrotic and unaffected bone were then performed by an expert reader to train a self-configuring nnU-Net model. Testing of the network performance was performed using a 5-fold cross-validation and Dice coefficients were calculated. In addition, performance across the three segmentations were compared using six parameters: volume of necrosis, volume of unaffected bone, percent of necrotic bone volume, surface of necrotic bone, unaffected femoral head surface, and percent of necrotic femoral head surface area. (3) Results: Comparison between the manual 3D and manual 2D segmentations as well as 2D with the automatic model yielded significant, strong correlations (R_p > 0.9) across all six parameters of necrosis. Dice coefficients between manual- and automated 2D segmentations of necrotic- and unaffected bone were 75 ± 15% and 91 ± 5%, respectively. None of the six parameters of FHN differed between the manual and automated 2D segmentations and showed strong correlations (R_p > 0.9). Necrotic volume and surface area showed significant differences (all p < 0.05) between early and advanced ARCO grading as opposed to the modified Kerboul angle, which was comparable between both groups (p > 0.05). (4) Conclusions: Our deep learning model to automatically segment femoral necrosis based on a routine hip MRI was highly accurate. Coupled with improved quantification for volume and surface area, as opposed to 2D angles, staging and course of treatment can become better tailored to patients with varying degrees of AVN. Full article

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

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13 pages, 828 KiB

Open AccessEditor’s ChoiceArticle

The Association between Alexithymia and Social Media Addiction: Exploring the Role of Dysmorphic Symptoms, Symptoms Interference, and Self-Esteem, Controlling for Age and Gender

by Alessio Gori and Eleonora Topino

J. Pers. Med. 2023, 13(1), 152; https://doi.org/10.3390/jpm13010152 - 12 Jan 2023

Cited by 10 | Viewed by 3795

Abstract

Given the popularity of social media and the growing presence of these tools in the daily lives of individuals, research about the elements that can be linked to their problematic use appears to be of great importance. The objective of this study was [...] Read more.

Given the popularity of social media and the growing presence of these tools in the daily lives of individuals, research about the elements that can be linked to their problematic use appears to be of great importance. The objective of this study was to investigate the factors that may contribute to the levels of social media addiction, by focusing on the role of alexithymia, body image concern, and self-esteem, controlled for age and gender. A sample of 437 social media users (32.5% men, 67.5% women; M_age = 33.44 years, SD = 13.284) completed an online survey, including the Bergen Social Media Addiction Scale, Body Image Concern Inventory, Rosenberg Self-Esteem Scale, and Twenty-Item Toronto Alexithymia Scale, together with a demographic questionnaire. Results showed a significant association between alexithymia and social media addiction, with the total mediation of body image concern (and more in detail, body dissatisfaction) and the significant moderation of self-esteem. Gender and age showed significant effects in these relationships. Such findings may offer further insights into the field of clinical research on social media addiction and may provide useful information for effective clinical practice. Full article

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17 pages, 873 KiB

Open AccessEditor’s ChoiceReview

Management of Hyponatremia in Heart Failure: Practical Considerations

by Victoriţa Şorodoc, Andreea Asaftei, Gabriela Puha, Alexandr Ceasovschih, Cătălina Lionte, Oana Sîrbu, Cristina Bologa, Raluca Ecaterina Haliga, Mihai Constantin, Adorata Elena Coman, Ovidiu Rusalim Petriș, Alexandra Stoica and Laurenţiu Şorodoc

J. Pers. Med. 2023, 13(1), 140; https://doi.org/10.3390/jpm13010140 - 10 Jan 2023

Cited by 4 | Viewed by 12738

Abstract

Hyponatremia is commonly encountered in the setting of heart failure, especially in decompensated, fluid-overloaded patients. The pathophysiology of hyponatremia in patients with heart failure is complex, including numerous mechanisms: increased activity of the sympathetic nervous system and the renin–angiotensin–aldosterone system, high levels of [...] Read more.

Hyponatremia is commonly encountered in the setting of heart failure, especially in decompensated, fluid-overloaded patients. The pathophysiology of hyponatremia in patients with heart failure is complex, including numerous mechanisms: increased activity of the sympathetic nervous system and the renin–angiotensin–aldosterone system, high levels of arginine vasopressin and diuretic use. Symptoms are usually mild but hyponatremic encephalopathy can occur if there is an acute decrease in serum sodium levels. It is crucial to differentiate between dilutional hyponatremia, where free water excretion should be promoted, and depletional hyponatremia, where administration of saline is needed. An inappropriate correction of hyponatremia may lead to osmotic demyelination syndrome which can cause severe neurological symptoms. Treatment options for hyponatremia in heart failure, such as water restriction or the use of hypertonic saline with loop diuretics, have limited efficacy. The aim of this review is to summarize the principal mechanisms involved in the occurrence of hyponatremia, to present the main guidelines for the treatment of hyponatremia, and to collect and analyze data from studies which target new treatment options, such as vaptans. Full article

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

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13 pages, 1267 KiB

Open AccessEditor’s ChoiceArticle

Epidemiology and Risk Factors of UTIs in Children—A Single-Center Observation

by Maria Daniel, Hanna Szymanik-Grzelak, Janusz Sierdziński, Edyta Podsiadły, Magdalena Kowalewska-Młot and Małgorzata Pańczyk-Tomaszewska

J. Pers. Med. 2023, 13(1), 138; https://doi.org/10.3390/jpm13010138 - 10 Jan 2023

Cited by 9 | Viewed by 2792

Abstract

Urinary tract infections (UTIs) are one of childhood’s most common bacterial infections. The study aimed to determine the clinical symptoms, laboratory tests, risk factors, and etiology of different UTIs in children admitted to pediatric hospitals for three years. Methods: Patients with positive urine [...] Read more.

Urinary tract infections (UTIs) are one of childhood’s most common bacterial infections. The study aimed to determine the clinical symptoms, laboratory tests, risk factors, and etiology of different UTIs in children admitted to pediatric hospitals for three years. Methods: Patients with positive urine cultures diagnosed with acute pyelonephritis (APN) or cystitis (CYS) were analyzed for clinical symptoms, laboratory tests, risk factors, and etiology, depending on their age and sex. Results: We studied 948 children with UTIs (531 girls and 417 boys), with a median age of 12 (IQR 5–48 months). A total of 789 children had clinical symptoms; the main symptom was fever (63.4% of patients). Specific symptoms of UTIs were presented only in 16.3% of patients. Children with APN had shown significantly more frequent loss of appetite, vomiting, lethargy, seizures, and less frequent dysuria and haematuria than children with CYS. We found significantly higher median WBC, CRP, and leukocyturia in children with APN than with CYS. The risk factors of UTIs were presented in 46.6% of patients, of which 35.6% were children with APN and 61.7% with CYS. The main risk factor was CAKUT, more frequently diagnosed in children with CYS than APN, mainly in children <2 years. The most commonly isolated bacteria were Escherichia coli (74%). There was a higher percentage of urine samples with E. coli in girls than in boys. Other bacteria found were Klebsiella species, Pseudomonas aeruginosa, Proteus mirabilis, and Enterococcus species. Conclusions: Patients with APN were younger and had higher inflammatory markers. Often, fever is the only symptom of UTI in children, and other clinical signs are usually non-specific. The most common UTI etiology is E. coli, regardless of the clinical presentation and risk factors. Full article

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

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24 pages, 6394 KiB

Open AccessEditor’s ChoiceReview

Three-Dimensional Accuracy and Stability of Personalized Implants in Orthognathic Surgery: A Systematic Review and a Meta-Analysis

by Alexandru Diaconu, Michael Boelstoft Holte, Gabriele Berg-Beckhoff and Else Marie Pinholt

J. Pers. Med. 2023, 13(1), 125; https://doi.org/10.3390/jpm13010125 - 07 Jan 2023

Cited by 8 | Viewed by 2386

Abstract

This systematic review aimed to determine the accuracy/stability of patient-specific osteosynthesis (PSI) in orthognathic surgery according to three-dimensional (3D) outcome analysis and in comparison to conventional osteosynthesis and computer-aided designed and manufactured (CAD/CAM) splints or wafers. The PRISMA guidelines were followed and six [...] Read more.

This systematic review aimed to determine the accuracy/stability of patient-specific osteosynthesis (PSI) in orthognathic surgery according to three-dimensional (3D) outcome analysis and in comparison to conventional osteosynthesis and computer-aided designed and manufactured (CAD/CAM) splints or wafers. The PRISMA guidelines were followed and six academic databases and Google Scholar were searched. Records reporting 3D accuracy/stability measurements of bony segments fixated with PSI were included. Of 485 initial records, 21 met the eligibility (566 subjects), nine of which also qualified for a meta-analysis (164 subjects). Six studies had a high risk of bias (29%), and the rest were of low or moderate risk. Procedures comprised either single-piece or segmental Le Fort I and/or mandibular osteotomy and/or genioplasty. A stratified meta-analysis including 115 subjects with single-piece Le Fort I PSI showed that the largest absolute mean deviations were 0.5 mm antero-posteriorly and 0.65° in pitch. PSIs were up to 0.85 mm and 2.35° more accurate than conventional osteosynthesis with CAD/CAM splint or wafer (p < 0.0001). However, the clinical relevance of the improved accuracy has not been shown. The literature on PSI for multi-piece Le Fort I, mandibular osteotomies and genioplasty procedure is characterized by high methodological heterogeneity and a lack of randomized controlled trials. The literature is lacking on the 3D stability of bony segments fixated with PSI. Full article

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

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12 pages, 629 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Combining Clinical and Genetic Data to Predict Response to Fingolimod Treatment in Relapsing Remitting Multiple Sclerosis Patients: A Precision Medicine Approach

by Laura Ferrè, Ferdinando Clarelli, Beatrice Pignolet, Elisabetta Mascia, Marco Frasca, Silvia Santoro, Melissa Sorosina, Florence Bucciarelli, Lucia Moiola, Vittorio Martinelli, Giancarlo Comi, Roland Liblau, Massimo Filippi, Giorgio Valentini and Federica Esposito

J. Pers. Med. 2023, 13(1), 122; https://doi.org/10.3390/jpm13010122 - 06 Jan 2023

Cited by 3 | Viewed by 1561

Abstract

A personalized approach is strongly advocated for treatment selection in Multiple Sclerosis patients due to the high number of available drugs. Machine learning methods proved to be valuable tools in the context of precision medicine. In the present work, we applied machine learning [...] Read more.

A personalized approach is strongly advocated for treatment selection in Multiple Sclerosis patients due to the high number of available drugs. Machine learning methods proved to be valuable tools in the context of precision medicine. In the present work, we applied machine learning methods to identify a combined clinical and genetic signature of response to fingolimod that could support the prediction of drug response. Two cohorts of fingolimod-treated patients from Italy and France were enrolled and divided into training, validation, and test set. Random forest training and robust feature selection were performed in the first two sets respectively, and the independent test set was used to evaluate model performance. A genetic-only model and a combined clinical–genetic model were obtained. Overall, 381 patients were classified according to the NEDA-3 criterion at 2 years; we identified a genetic model, including 123 SNPs, that was able to predict fingolimod response with an AUROC= 0.65 in the independent test set. When combining clinical data, the model accuracy increased to an AUROC= 0.71. Integrating clinical and genetic data by means of machine learning methods can help in the prediction of response to fingolimod, even though further studies are required to definitely extend this approach to clinical applications Full article

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20 pages, 1459 KiB

Open AccessEditor’s ChoiceReview

Medical and Surgical Strategies in Vulvar Paget Disease: Let’s Throw Some Light!

by Luigi Della Corte, Valeria Cafasso, Carmine Conte, Lara Cuomo, Pierluigi Giampaolino, Giada Lavitola and Giuseppe Bifulco

J. Pers. Med. 2023, 13(1), 100; https://doi.org/10.3390/jpm13010100 - 01 Jan 2023

Cited by 2 | Viewed by 1754

Abstract

Background: Vulvar Paget’s disease (VPD) is defined as a neoplasm of epithelial origin, mostly in postmenopausal women. Due to the extreme rarity of VPD, limited data about recommended treatment options are available. Surgical excision has been the treatment of choice although in the [...] Read more.

Background: Vulvar Paget’s disease (VPD) is defined as a neoplasm of epithelial origin, mostly in postmenopausal women. Due to the extreme rarity of VPD, limited data about recommended treatment options are available. Surgical excision has been the treatment of choice although in the recent decade medical treatments have been proposed. Methods: A systematic computerized search of the literature was performed in the main electronic databases (MEDLINE, EMBASE, Web of Science, PubMed, and Cochrane Library), from 2003 to September 2022, in order to analyze all medical and surgical strategies used for the treatment of VPD. Results: Thirty-four articles were included in this review with findings as follows: 390 patients were treated with medical or other conservative treatment while 2802 patients were treated surgically; 235/434 (54%) patients had a complete response, 67/434 (15%) a partial response, 10/434 (2.3%) a stable disease, 3/434 (0.7%) disease progress, 3/434 (0.7%) died of the disease, 55/434 (13%) died of other causes during follow up while 7/434 (1.6%) had to stop topical treatments with 5% imiquimod cream because of side effects; 239/434 patients (55%) had a recurrence and 11/434 (2.5%) were lost to follow-up. The length of follow-up was variable, according to the different studies analyzed. Conclusion: VPD is a chronic disease with a high recurrence rate and low mortality. There are no significant differences in recurrence rates in patients who undergo surgery and those who do not and the margin status at the time of primary surgery and recurrence. Several surgical and medical approaches providing both local control of the disease and minimal tissue damage have been developed. Clock mapping, a recent preoperative vulvo-vaginal workup tool, can predict the invasiveness and the extension of VPD. However, to date, due to the different treatment options available and in the absence of a global consensus, it is critical to tailor treatments to individual patient characteristics and biopsy histopathologic findings, to ensure the best type of therapy. Full article

(This article belongs to the Special Issue Gynecological Surgery: Current Perspectives and Future Challenges)

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16 pages, 1739 KiB

Open AccessEditor’s ChoiceArticle

The Penn Medicine BioBank: Towards a Genomics-Enabled Learning Healthcare System to Accelerate Precision Medicine in a Diverse Population

by Anurag Verma, Scott M. Damrauer, Nawar Naseer, JoEllen Weaver, Colleen M. Kripke, Lindsay Guare, Giorgio Sirugo, Rachel L. Kember, Theodore G. Drivas, Scott M. Dudek, Yuki Bradford, Anastasia Lucas, Renae Judy, Shefali S. Verma, Emma Meagher, Katherine L. Nathanson, Michael Feldman, Marylyn D. Ritchie, Daniel J. Rader and For The Penn Medicine BioBank

J. Pers. Med. 2022, 12(12), 1974; https://doi.org/10.3390/jpm12121974 - 29 Nov 2022

Cited by 24 | Viewed by 2982

Abstract

The Penn Medicine BioBank (PMBB) is an electronic health record (EHR)-linked biobank at the University of Pennsylvania (Penn Medicine). A large variety of health-related information, ranging from diagnosis codes to laboratory measurements, imaging data and lifestyle information, is integrated with genomic and biomarker [...] Read more.

The Penn Medicine BioBank (PMBB) is an electronic health record (EHR)-linked biobank at the University of Pennsylvania (Penn Medicine). A large variety of health-related information, ranging from diagnosis codes to laboratory measurements, imaging data and lifestyle information, is integrated with genomic and biomarker data in the PMBB to facilitate discoveries and translational science. To date, 174,712 participants have been enrolled into the PMBB, including approximately 30% of participants of non-European ancestry, making it one of the most diverse medical biobanks. There is a median of seven years of longitudinal data in the EHR available on participants, who also consent to permission to recontact. Herein, we describe the operations and infrastructure of the PMBB, summarize the phenotypic architecture of the enrolled participants, and use body mass index (BMI) as a proof-of-concept quantitative phenotype for PheWAS, LabWAS, and GWAS. The major representation of African-American participants in the PMBB addresses the essential need to expand the diversity in genetic and translational research. There is a critical need for a “medical biobank consortium” to facilitate replication, increase power for rare phenotypes and variants, and promote harmonized collaboration to optimize the potential for biological discovery and precision medicine. Full article

(This article belongs to the Special Issue Genomic Medicine Cohorts Based at U.S. Health Systems and Health Centers)

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20 pages, 2985 KiB

Open AccessEditor’s ChoiceReview

Enhanced Permeability and Retention Effect as a Ubiquitous and Epoch-Making Phenomenon for the Selective Drug Targeting of Solid Tumors

by Waliul Islam, Takuro Niidome and Tomohiro Sawa

J. Pers. Med. 2022, 12(12), 1964; https://doi.org/10.3390/jpm12121964 - 28 Nov 2022

Cited by 12 | Viewed by 3428

Abstract

In 1979, development of the first polymer drug SMANCS [styrene-co-maleic acid (SMA) copolymer conjugated to neocarzinostatin (NCS)] by Maeda and colleagues was a breakthrough in the cancer field. When SMANCS was administered to mice, drug accumulation in tumors was markedly increased compared with [...] Read more.

In 1979, development of the first polymer drug SMANCS [styrene-co-maleic acid (SMA) copolymer conjugated to neocarzinostatin (NCS)] by Maeda and colleagues was a breakthrough in the cancer field. When SMANCS was administered to mice, drug accumulation in tumors was markedly increased compared with accumulation of the parental drug NCS. This momentous result led to discovery of the enhanced permeability and retention effect (EPR effect) in 1986. Later, the EPR effect became known worldwide, especially in nanomedicine, and is still believed to be a universal mechanism for tumor-selective accumulation of nanomedicines. Some research groups recently characterized the EPR effect as a controversial concept and stated that it has not been fully demonstrated in clinical settings, but this erroneous belief is due to non-standard drug design and use of inappropriate tumor models in investigations. Many research groups recently provided solid evidence of the EPR effect in human cancers (e.g., renal and breast), with significant diversity and heterogeneity in various patients. In this review, we focus on the dynamics of the EPR effect and restoring tumor blood flow by using EPR effect enhancers. We also discuss new applications of EPR-based nanomedicine in boron neutron capture therapy and photodynamic therapy for solid tumors. Full article

(This article belongs to the Special Issue EPR Effect-Based Cancer Targeted Therapy: Commemorative Issue in Honor of Professor Hiroshi Maeda)

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21 pages, 624 KiB

Open AccessEditor’s ChoiceReview

Multimorbidity, Frailty and Diabetes in Older People–Identifying Interrelationships and Outcomes

by Alan J. Sinclair and Ahmed H. Abdelhafiz

J. Pers. Med. 2022, 12(11), 1911; https://doi.org/10.3390/jpm12111911 - 16 Nov 2022

Cited by 11 | Viewed by 2195

Abstract

Multimorbidity and frailty are highly prevalent in older people with diabetes. This high prevalence is likely due to a combination of ageing and diabetes-related complications and other diabetes-associated comorbidities. Both multimorbidity and frailty are associated with a wide range of adverse outcomes in [...] Read more.

Multimorbidity and frailty are highly prevalent in older people with diabetes. This high prevalence is likely due to a combination of ageing and diabetes-related complications and other diabetes-associated comorbidities. Both multimorbidity and frailty are associated with a wide range of adverse outcomes in older people with diabetes, which are proportionally related to the number of morbidities and to the severity of frailty. Although, the multimorbidity pattern or cluster of morbidities that have the most adverse effect are not yet well defined, it appears that mental health disorders enhance the multimorbidity-related adverse outcomes. Therefore, comprehensive diabetes guidelines that incorporate a holistic approach that includes screening and management of mental health disorders such as depression is required. The adverse outcomes predicted by multimorbidity and frailty appear to be similar and include an increased risk of health care utilisation, disability and mortality. The differential effect of one condition on outcomes, independent of the other, still needs future exploration. In addition, prospective clinical trials are required to investigate whether interventions to reduce multimorbidity and frailty both separately and in combination would improve clinical outcomes. Full article

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20 pages, 4380 KiB

Open AccessEditor’s ChoiceArticle

Nontraumatic Spinal Cord Injury: Epidemiology, Etiology and Management

by Diana M. Molinares, David R. Gater, Scott Daniel and Nicole L. Pontee

J. Pers. Med. 2022, 12(11), 1872; https://doi.org/10.3390/jpm12111872 - 08 Nov 2022

Cited by 15 | Viewed by 3934

Abstract

The spinal cord is a conduit within the central nervous system (CNS) that provides ongoing communication between the brain and the rest of the body, conveying complex sensory and motor information necessary for safety, movement, reflexes, and optimization of autonomic function. After a [...] Read more.

The spinal cord is a conduit within the central nervous system (CNS) that provides ongoing communication between the brain and the rest of the body, conveying complex sensory and motor information necessary for safety, movement, reflexes, and optimization of autonomic function. After a traumatic spinal cord injury (SCI), supraspinal influences on the peripheral nervous system and autonomic nervous system (ANS) are disrupted, leading to spastic paralysis, sympathetic blunting, and parasympathetic dominance, resulting in cardiac dysrhythmias, systemic hypotension, bronchoconstriction, copious respiratory secretions, and uncontrolled bowel, bladder, and sexual dysfunction. This article outlines the pathophysiology of the less reported nontraumatic SCI (NTSCI), its classification, its influence on sensory/motor function, and introduces the probable comorbidities associated with SCI that will be discussed in more detail in the accompanying manuscripts of this special issue. Finally, management strategies for NTSCI will be provided. Full article

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

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16 pages, 1241 KiB

Open AccessEditor’s ChoiceReview

The Cellular and Molecular Signature of ALS in Muscle

by Ekene Anakor, William John Duddy and Stephanie Duguez

J. Pers. Med. 2022, 12(11), 1868; https://doi.org/10.3390/jpm12111868 - 08 Nov 2022

Cited by 7 | Viewed by 2423

Abstract

Amyotrophic lateral sclerosis is a disease affecting upper and lower motor neurons. Although motor neuron death is the core event of ALS pathology, it is increasingly recognized that other tissues and cell types are affected in the disease, making potentially major contributions to [...] Read more.

Amyotrophic lateral sclerosis is a disease affecting upper and lower motor neurons. Although motor neuron death is the core event of ALS pathology, it is increasingly recognized that other tissues and cell types are affected in the disease, making potentially major contributions to the occurrence and progression of pathology. We review here the known cellular and molecular characteristics of muscle tissue affected by ALS. Evidence of toxicity in skeletal muscle tissue is considered, including metabolic dysfunctions, impaired proteostasis, and deficits in muscle regeneration and RNA metabolism. The role of muscle as a secretory organ, and effects on the skeletal muscle secretome are also covered, including the increase in secretion of toxic factors or decrease in essential factors that have consequences for neuronal function and survival. Full article

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

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13 pages, 793 KiB

Open AccessEditor’s ChoiceReview

Short-Chain Fatty Acids in Gut–Heart Axis: Their Role in the Pathology of Heart Failure

by Midori Yukino-Iwashita, Yuji Nagatomo, Akane Kawai, Akira Taruoka, Yusuke Yumita, Kazuki Kagami, Risako Yasuda, Takumi Toya, Yukinori Ikegami, Nobuyuki Masaki, Yasuo Ido and Takeshi Adachi

J. Pers. Med. 2022, 12(11), 1805; https://doi.org/10.3390/jpm12111805 - 01 Nov 2022

Cited by 11 | Viewed by 2714

Abstract

Heart failure (HF) is a syndrome with global clinical and socioeconomic burden worldwide owing to its poor prognosis. Accumulating evidence has implicated the possible contribution of gut microbiota-derived metabolites, short-chain fatty acids (SCFAs), on the pathology of a variety of diseases. The changes [...] Read more.

Heart failure (HF) is a syndrome with global clinical and socioeconomic burden worldwide owing to its poor prognosis. Accumulating evidence has implicated the possible contribution of gut microbiota-derived metabolites, short-chain fatty acids (SCFAs), on the pathology of a variety of diseases. The changes of SCFA concentration were reported to be observed in various cardiovascular diseases including HF in experimental animals and humans. HF causes hypoperfusion and/or congestion in the gut, which may lead to lowered production of SCFAs, possibly through the pathological changes of the gut microenvironment including microbiota composition. Recent studies suggest that SCFAs may play a significant role in the pathology of HF, possibly through an agonistic effect on G-protein-coupled receptors, histone deacetylases (HDACs) inhibition, restoration of mitochondrial function, amelioration of cardiac inflammatory response, its utilization as an energy source, and remote effect attributable to a protective effect on the other organs. Collectively, in the pathology of HF, SCFAs might play a significant role as a key mediator in the gut–heart axis. However, these possible mechanisms have not been entirely clarified and need further investigation. Full article

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

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13 pages, 724 KiB

Open AccessEditor’s ChoiceReview

Advanced Bladder Cancer: Changing the Treatment Landscape

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

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

Cited by 14 | Viewed by 3100

Abstract

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

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

(This article belongs to the Section Mechanisms of Diseases)

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14 pages, 3045 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 11 | Viewed by 2025

Abstract

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

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

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

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13 pages, 1607 KiB

Open AccessEditor’s ChoiceArticle

Clinical Significance of the Histone Deacetylase 2 (HDAC-2) Expression in Human Breast Cancer

by Nikolaos Garmpis, Christos Damaskos, Dimitrios Dimitroulis, Gregory Kouraklis, Anna Garmpi, Panagiotis Sarantis, Evangelos Koustas, Alexandros Patsouras, Iason Psilopatis, Efstathios A. Antoniou, Michail V. Karamouzis, Konstantinos Kontzoglou and Afroditi Nonni

J. Pers. Med. 2022, 12(10), 1672; https://doi.org/10.3390/jpm12101672 - 08 Oct 2022

Cited by 10 | Viewed by 1483

Abstract

Background/Aim: There is a strong association between malignancy and histone deacetylases (HDACs). Histone deacetylase inhibitors (HDACIs) are now being tested as antitumor agents in various clinical trials. We aimed to assess the clinical importance of HDAC-2 in breast cancer (BC). Materials and Methods: [...] Read more.

Background/Aim: There is a strong association between malignancy and histone deacetylases (HDACs). Histone deacetylase inhibitors (HDACIs) are now being tested as antitumor agents in various clinical trials. We aimed to assess the clinical importance of HDAC-2 in breast cancer (BC). Materials and Methods: A total of 118 BC specimens were examined immunohistochemically. A statistical analysis was conducted in order to examine the relation between HDAC-2 and the clinicopathological features and survival of the patients. Results: Higher HDAC-2 expression was related to lobular histological type of cancer, grade III, and stage III BC. In addition, the disease-free period and overall survival were curtailed and negatively related to the over-expression of HDAC-2. Other factors correlating with worse survival were histological types other than ductal or lobular, and the stage of the disease. Conclusions: This study showed a relationship between HDAC-2 and BC. Further studies are required in order to eventually potentiate the role of HDACIs as anticancer agents in BC. Full article

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

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14 pages, 2277 KiB

Open AccessEditor’s ChoiceArticle

An Epidemiological and Etiological Analysis of 5026 Peripheral Nerve Lesions from a European Level I Trauma Center

by Martin Aman, Kim S. Zimmermann, Mirjam Thielen, Benjamin Thomas, Simeon Daeschler, Arne H. Boecker, Annette Stolle, Amir K. Bigdeli, Ulrich Kneser and Leila Harhaus

J. Pers. Med. 2022, 12(10), 1673; https://doi.org/10.3390/jpm12101673 - 08 Oct 2022

Cited by 13 | Viewed by 1364

Abstract

Background: Peripheral nerve lesions are associated with debilitating long-term consequences. Albeit being essential for evidence-based clinical decision making, epidemiological and etiological data are scarce. We therefore aimed to comprehensively analyze epidemiological and etiological factors of peripheral nerve lesions in one of the largest [...] Read more.

Background: Peripheral nerve lesions are associated with debilitating long-term consequences. Albeit being essential for evidence-based clinical decision making, epidemiological and etiological data are scarce. We therefore aimed to comprehensively analyze epidemiological and etiological factors of peripheral nerve lesions in one of the largest cohorts. Methods: We screened a total of 110,667 patients treated at our level I trauma center between January 2012 and July 2020 for nerve lesions. Subsequently, demographics, etiologies, concomitant injuries, and lesion characteristics were analyzed. Results: A total of 5026 patients, predominantly young males suffering from non-work-related nerve injuries, were treated. Proximal levels of injury were more likely to be accompanied by fractures, whereas more distal injuries with concomitant vessel or tendon injury. Main causes were 54.6% lacerations. Acute traumatic nerve injury was treated within 24 h in 55.9% of cases. Conclusions: Given the young age of affected patients, early diagnosis and treatment in specialized centers may facilitate their early return to work and improve long-term functional outcomes. The data show the importance of a special attention on nerve injuries, which may be masked by large accompanying injuries. New findings on lesion characteristics of selected subgroups and accompanying circumstances can support a change in treatment strategies. Full article

(This article belongs to the Special Issue Diagnosis and Treatment in Peripheral Nerve Surgery)

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15 pages, 687 KiB

Open AccessEditor’s ChoiceReview

Contemporary Management of Severely Calcified Coronary Lesions

by Natthapon Angsubhakorn, Nicolas Kang, Colleen Fearon, Chol Techorueangwiwat, Pooja Swamy, Emmanouil S. Brilakis and Aditya S. Bharadwaj

J. Pers. Med. 2022, 12(10), 1638; https://doi.org/10.3390/jpm12101638 - 03 Oct 2022

Cited by 9 | Viewed by 4170

Abstract

Coronary artery calcification is increasingly prevalent in our patient population. It significantly limits the procedural success of percutaneous coronary intervention and is associated with a higher risk of adverse cardiovascular events both in the short-term and long-term. There are several modalities for modifying [...] Read more.

Coronary artery calcification is increasingly prevalent in our patient population. It significantly limits the procedural success of percutaneous coronary intervention and is associated with a higher risk of adverse cardiovascular events both in the short-term and long-term. There are several modalities for modifying calcified plaque, such as balloon angioplasty (including specialty balloons), coronary atheroablative therapy (rotational, orbital, and laser atherectomy), and intravascular lithotripsy. We discuss each modality’s relative advantages and disadvantages and the data supporting their use. This review also highlights the importance of intravascular imaging to characterize coronary calcification and presents an algorithm to tailor the calcium modification therapy based on specific coronary lesion characteristics. Full article

(This article belongs to the Special Issue Novel Challenges and Advances in Complex Coronary Interventions)

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15 pages, 893 KiB

Open AccessEditor’s ChoiceReview

Status of ALS Treatment, Insights into Therapeutic Challenges and Dilemmas

by Mohammed Khamaysa and Pierre-François Pradat

J. Pers. Med. 2022, 12(10), 1601; https://doi.org/10.3390/jpm12101601 - 28 Sep 2022

Cited by 10 | Viewed by 3878

Abstract

Amyotrophic lateral sclerosis (ALS) is an extremely heterogeneous disease of motor neurons that eventually leads to death. Despite impressive advances in understanding the genetic, molecular, and pathological mechanisms of the disease, the only drug approved to date by both the FDA and EMA [...] Read more.

Amyotrophic lateral sclerosis (ALS) is an extremely heterogeneous disease of motor neurons that eventually leads to death. Despite impressive advances in understanding the genetic, molecular, and pathological mechanisms of the disease, the only drug approved to date by both the FDA and EMA is riluzole, with a modest effect on survival. In this opinion view paper, we will discuss how to address some challenges for drug development in ALS at the conceptual, technological, and methodological levels. In addition, socioeconomic and ethical issues related to the legitimate need of patients to benefit quickly from new treatments will also be addressed. In conclusion, this brief review takes a more optimistic view, given the recent approval of two new drugs in some countries and the development of targeted gene therapies. Full article

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

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15 pages, 977 KiB

Open AccessEditor’s ChoiceArticle

Comparative Analysis between Individual, Centralized, and Federated Learning for Smartwatch Based Stress Detection

by Muhammad Ali Fauzi, Bian Yang and Bernd Blobel

J. Pers. Med. 2022, 12(10), 1584; https://doi.org/10.3390/jpm12101584 - 26 Sep 2022

Cited by 9 | Viewed by 2701

Abstract

Machine learning has been proven to provide good performances on stress detection tasks using multi-modal sensor data from a smartwatch. Generally, machine learning techniques need a sufficient amount of data to train a robust model. Thus, we need to collect data from several [...] Read more.

Machine learning has been proven to provide good performances on stress detection tasks using multi-modal sensor data from a smartwatch. Generally, machine learning techniques need a sufficient amount of data to train a robust model. Thus, we need to collect data from several users and send them to a central server to feed the algorithm. However, the uploaded data may contain sensitive information that can jeopardize the user’s privacy. Federated learning can tackle this challenge by enabling the model to be trained using data from all users without the user’s data leaving the user’s device. In this study, we implement federated learning-based stress detection and provide a comparative analysis between individual, centralized, and federated learning. The experiment was conducted on WESAD dataset by using Logistic Regression as the classifier. The experiment results show that in terms of accuracy, federated learning cannot reach the performance level of both individual and centralized learning. The individual learning strategy performs best with an average accuracy of 0.9998 and an average F₁-measure of 0.9996. Full article

(This article belongs to the Special Issue Selected Papers from the pHealth 2021 Conference, Genoa, Italy, 8-10 November 2021)

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13 pages, 926 KiB

Open AccessEditor’s ChoiceReview

Delayed Graft Function in Kidney Transplant: Risk Factors, Consequences and Prevention Strategies

by Claudio Ponticelli, Francesco Reggiani and Gabriella Moroni

J. Pers. Med. 2022, 12(10), 1557; https://doi.org/10.3390/jpm12101557 - 21 Sep 2022

Cited by 15 | Viewed by 3270

Abstract

Background. Delayed graft function is a frequent complication of kidney transplantation that requires dialysis in the first week posttransplant. Materials and Methods. We searched for the most relevant articles in the National Institutes of Health library of medicine, as well as in transplantation, [...] Read more.

Background. Delayed graft function is a frequent complication of kidney transplantation that requires dialysis in the first week posttransplant. Materials and Methods. We searched for the most relevant articles in the National Institutes of Health library of medicine, as well as in transplantation, pharmacologic, and nephrological journals. Results. The main factors that may influence the development of delayed graft function (DGF) are ischemia–reperfusion injury, the source and the quality of the donated kidney, and the clinical management of the recipient. The pathophysiology of ischemia–reperfusion injury is complex and involves kidney hypoxia related to the duration of warm and cold ischemia, as well as the harmful effects of blood reperfusion on tubular epithelial cells and endothelial cells. Ischemia–reperfusion injury is more frequent and severe in kidneys from deceased donors than in those from living donors. Of great importance is the quality and function of the donated kidney. Kidneys from living donors and those with normal function can provide better results. In the peri-operative management of the recipient, great attention should be paid to hemodynamic stability and blood pressure; nephrotoxic medicaments should be avoided. Over time, patients with DGF may present lower graft function and survival compared to transplant recipients without DGF. Maladaptation repair, mitochondrial dysfunction, and acute rejection may explain the worse long-term outcome in patients with DGF. Many different strategies meant to prevent DGF have been evaluated, but only prolonged perfusion of dopamine and hypothermic machine perfusion have proven to be of some benefit. Whenever possible, a preemptive transplant from living donor should be preferred. Full article

(This article belongs to the Special Issue Personalized Medicine in Kidney Transplantation and Immunology)

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21 pages, 3238 KiB

Open AccessEditor’s ChoiceArticle

Image Analysis in Digital Pathology Utilizing Machine Learning and Deep Neural Networks

by Paris Amerikanos and Ilias Maglogiannis

J. Pers. Med. 2022, 12(9), 1444; https://doi.org/10.3390/jpm12091444 - 01 Sep 2022

Cited by 10 | Viewed by 2496

Abstract

Detection of regions of interest (ROIs) in whole slide images (WSIs) in a clinical setting is a highly subjective and a labor-intensive task. In this work, recent developments in machine learning and computer vision algorithms are presented to assess their possible usage and [...] Read more.

Detection of regions of interest (ROIs) in whole slide images (WSIs) in a clinical setting is a highly subjective and a labor-intensive task. In this work, recent developments in machine learning and computer vision algorithms are presented to assess their possible usage and performance to enhance and accelerate clinical pathology procedures, such as ROI detection in WSIs. In this context, a state-of-the-art deep learning framework (Detectron2) was trained on two cases linked to the TUPAC16 dataset for object detection and on the JPATHOL dataset for instance segmentation. The predictions were evaluated against competing models and further possible improvements are discussed. Full article

(This article belongs to the Special Issue Development and Application of Bioinformatics in Personalized Medicine)

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11 pages, 902 KiB

Open AccessEditor’s ChoiceReview

Ultrathin Struts Drug-Eluting Stents: A State-of-the-Art Review

by Attilio Leone, Fiorenzo Simonetti, Marisa Avvedimento, Domenico Angellotti, Maddalena Immobile Molaro, Anna Franzone, Giovanni Esposito and Raffaele Piccolo

J. Pers. Med. 2022, 12(9), 1378; https://doi.org/10.3390/jpm12091378 - 25 Aug 2022

Cited by 10 | Viewed by 5026

Abstract

New-generation drug-eluting stents (DESs) represent the standard of care for patients undergoing percutaneous coronary intervention (PCI). Recent iterations in DES technology have led to the development of newer stent platforms with a further reduction in strut thickness. This new DES class, known as [...] Read more.

New-generation drug-eluting stents (DESs) represent the standard of care for patients undergoing percutaneous coronary intervention (PCI). Recent iterations in DES technology have led to the development of newer stent platforms with a further reduction in strut thickness. This new DES class, known as ultrathin struts DESs, has struts thinner than 70 µm. The evidence base for these devices consists of observational data, large-scale meta-analyses, and randomized trials with long-term follow-up, which have been conducted to investigate the difference between ultrathin struts DESs and conventional new-generation DESs in a variety of clinical settings and lesion subsets. Ultrathin struts DESs may further improve the efficacy and safety profile of PCI by reducing the risk of target-lesion and target-vessel failures in comparison to new-generation DESs. In this article, we reviewed device characteristics and clinical data of the Orsiro (Biotronik, Bülach, Switzerland), Coroflex ISAR (B. Braun Melsungen, Germany), BioMime (Meril Life Sciences Pvt. Ltd., Gujarat, India), MiStent (MiCell Technologies, USA), and Supraflex (Sahajanand Medical Technologies, Surat, India) sirolimus-eluting stents. Full article

(This article belongs to the Special Issue Novel Challenges and Advances in Complex Coronary Interventions)

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27 pages, 894 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Potential and Pitfalls of Mobile Mental Health Apps in Traditional Treatment: An Umbrella Review

by Jerica Koh, Germaine Y. Q. Tng and Andree Hartanto

J. Pers. Med. 2022, 12(9), 1376; https://doi.org/10.3390/jpm12091376 - 25 Aug 2022

Cited by 20 | Viewed by 5673

Abstract

While the rapid growth of mobile mental health applications has offered an avenue of support unbridled by physical distance, time, and cost, the digitalization of traditional interventions has also triggered doubts surrounding their effectiveness and safety. Given the need for a more comprehensive [...] Read more.

While the rapid growth of mobile mental health applications has offered an avenue of support unbridled by physical distance, time, and cost, the digitalization of traditional interventions has also triggered doubts surrounding their effectiveness and safety. Given the need for a more comprehensive and up-to-date understanding of mobile mental health apps in traditional treatment, this umbrella review provides a holistic summary of their key potential and pitfalls. A total of 36 reviews published between 2014 and 2022—including systematic reviews, meta-analyses, scoping reviews, and literature reviews—were identified from the Cochrane library, Medline (via PubMed Central), and Scopus databases. The majority of results supported the key potential of apps in helping to (1) provide timely support, (2) ease the costs of mental healthcare, (3) combat stigma in help-seeking, and (4) enhance therapeutic outcomes. Our results also identified common themes of apps’ pitfalls (i.e., challenges faced by app users), including (1) user engagement issues, (2) safety issues in emergencies, (3) privacy and confidentiality breaches, and (4) the utilization of non-evidence-based approaches. We synthesize the potential and pitfalls of mental health apps provided by the reviews and outline critical avenues for future research. Full article

(This article belongs to the Special Issue Digital Health and Telemedicine: Their Contribution to Personalized and Precision Medicine)

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14 pages, 4946 KiB

Open AccessEditor’s ChoiceArticle

Finetuned Super-Resolution Generative Adversarial Network (Artificial Intelligence) Model for Calcium Deblooming in Coronary Computed Tomography Angiography

by Zhonghua Sun and Curtise K. C. Ng

J. Pers. Med. 2022, 12(9), 1354; https://doi.org/10.3390/jpm12091354 - 23 Aug 2022

Cited by 10 | Viewed by 2178

Abstract

The purpose of this study was to finetune a deep learning model, real-enhanced super-resolution generative adversarial network (Real-ESRGAN), and investigate its diagnostic value in calcified coronary plaques with the aim of suppressing blooming artifacts for the further improvement of coronary lumen assessment. We [...] Read more.

The purpose of this study was to finetune a deep learning model, real-enhanced super-resolution generative adversarial network (Real-ESRGAN), and investigate its diagnostic value in calcified coronary plaques with the aim of suppressing blooming artifacts for the further improvement of coronary lumen assessment. We finetuned the Real-ESRGAN model and applied it to 50 patients with 184 calcified plaques detected at three main coronary arteries (left anterior descending [LAD], left circumflex [LCx] and right coronary artery [RCA]). Measurements of coronary stenosis were collected from original coronary computed tomography angiography (CCTA) and Real-ESRGAN-processed images, including Real-ESRGAN-high-resolution, Real-ESRGAN-average and Real-ESRGAN-median (Real-ESRGAN-HR, Real-ESRGAN-A and Real-ESRGAN-M) with invasive coronary angiography as the reference. Our results showed specificity and positive predictive value (PPV) of the Real-ESRGAN-processed images were improved at all of the three coronary arteries, leading to significant reduction in the false positive rates when compared to those of the original CCTA images. The specificity and PPV of the Real-ESRGAN-M images were the highest at the RCA level, with values being 80% (95% CI: 64.4%, 90.9%) and 61.9% (95% CI: 45.6%, 75.9%), although the sensitivity was reduced to 81.3% (95% CI: 54.5%, 95.9%) due to false negative results. The corresponding specificity and PPV of the Real-ESRGAN-M images were 51.9 (95% CI: 40.3%, 63.5%) and 31.5% (95% CI: 25.8%, 37.8%) at LAD, 62.5% (95% CI: 40.6%, 81.2%) and 43.8% (95% CI: 30.3%, 58.1%) at LCx, respectively. The area under the receiver operating characteristic curve was also the highest at the RCA with value of 0.76 (95% CI: 0.64, 0.89), 0.84 (95% CI: 0.73, 0.94), 0.85 (95% CI: 0.75, 0.95) and 0.73 (95% CI: 0.58, 0.89), corresponding to original CCTA, Real-ESRGAN-HR, Real-ESRGAN-A and Real-ESRGAN-M images, respectively. This study proves that the finetuned Real-ESRGAN model significantly improves the diagnostic performance of CCTA in assessing calcified plaques. Full article

(This article belongs to the Special Issue Personalized Medicine for Coronary Artery Disease: Diagnosis, Prevention, and Treatment)

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18 pages, 835 KiB

Open AccessEditor’s ChoiceArticle

The Evolution of a Large Biobank at Mass General Brigham

by Natalie T. Boutin, Samantha B. Schecter, Emma F. Perez, Natasha S. Tchamitchian, Xander R. Cerretani, Vivian S. Gainer, Matthew S. Lebo, Lisa M. Mahanta, Elizabeth W. Karlson and Jordan W. Smoller

J. Pers. Med. 2022, 12(8), 1323; https://doi.org/10.3390/jpm12081323 - 17 Aug 2022

Cited by 11 | Viewed by 1978

Abstract

The Mass General Brigham Biobank (formerly Partners HealthCare Biobank) is a large repository of biospecimens and data linked to extensive electronic health record data and survey data. Its objective is to support and enable translational research focused on genomic, environmental, biomarker and family [...] Read more.

The Mass General Brigham Biobank (formerly Partners HealthCare Biobank) is a large repository of biospecimens and data linked to extensive electronic health record data and survey data. Its objective is to support and enable translational research focused on genomic, environmental, biomarker and family history associations with disease phenotypes. The Biobank has enrolled more than 135,000 participants, generated genomic data on more than 65,000 of its participants, distributed approximately 153,000 biospecimens, and served close to 450 institutional studies with biospecimens or data. Although the Biobank has been successful, based on some measures of output, this has required substantial institutional investment. In addition, several challenges are ongoing, including: (1) developing a sustainable cost model that doesn’t rely as heavily on institutional funding; (2) integrating Biobank operations into clinical workflows; and (3) building a research resource that is diverse and promotes equity in research. Here, we describe the evolution of the Biobank and highlight key lessons learned that may inform other efforts to build biobanking efforts in health system contexts. Full article

(This article belongs to the Special Issue Genomic Medicine Cohorts Based at U.S. Health Systems and Health Centers)

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23 pages, 1233 KiB

Open AccessEditor’s ChoiceReview

Advances in Preclinical In Vitro Models for the Translation of Precision Medicine for Cystic Fibrosis

by Iris A. L. Silva, Onofrio Laselva and Miquéias Lopes-Pacheco

J. Pers. Med. 2022, 12(8), 1321; https://doi.org/10.3390/jpm12081321 - 16 Aug 2022

Cited by 14 | Viewed by 5093

Abstract

The development of preclinical in vitro models has provided significant progress to the studies of cystic fibrosis (CF), a frequently fatal monogenic disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. Numerous cell lines were generated over [...] Read more.

The development of preclinical in vitro models has provided significant progress to the studies of cystic fibrosis (CF), a frequently fatal monogenic disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. Numerous cell lines were generated over the last 30 years and they have been instrumental not only in enhancing the understanding of CF pathological mechanisms but also in developing therapies targeting the underlying defects in CFTR mutations with further validation in patient-derived samples. Furthermore, recent advances toward precision medicine in CF have been made possible by optimizing protocols and establishing novel assays using human bronchial, nasal and rectal tissues, and by progressing from two-dimensional monocultures to more complex three-dimensional culture platforms. These models also enable to potentially predict clinical efficacy and responsiveness to CFTR modulator therapies at an individual level. In parallel, advanced systems, such as induced pluripotent stem cells and organ-on-a-chip, continue to be developed in order to more closely recapitulate human physiology for disease modeling and drug testing. In this review, we have highlighted novel and optimized cell models that are being used in CF research to develop novel CFTR-directed therapies (or alternative therapeutic interventions) and to expand the usage of existing modulator drugs to common and rare CF-causing mutations. Full article

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

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13 pages, 535 KiB

Open AccessEditor’s ChoiceArticle

Mepolizumab Improves Outcomes of Chronic Rhinosinusitis with Nasal Polyps in Severe Asthmatic Patients: A Multicentric Real-Life Study

by Stefania Gallo, Paolo Castelnuovo, Luca Spirito, Marta Feduzi, Veronica Seccia, Dina Visca, Antonio Spanevello, Erica Statuti, Manuela Latorre, Claudio Montuori, Angela Rizzi, Cristina Boccabella, Matteo Bonini and Eugenio De Corso

J. Pers. Med. 2022, 12(8), 1304; https://doi.org/10.3390/jpm12081304 - 10 Aug 2022

Cited by 15 | Viewed by 2616

Abstract

Objective: The upcoming introduction of mepolizumab represents a promising treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). The present study aimed to evaluate the effectiveness of mepolizumab on sinonasal outcomes of comorbid CRSwNP and severe asthma in a real-life setting. The primary endpoint [...] Read more.

Objective: The upcoming introduction of mepolizumab represents a promising treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). The present study aimed to evaluate the effectiveness of mepolizumab on sinonasal outcomes of comorbid CRSwNP and severe asthma in a real-life setting. The primary endpoint was to evaluate changes in the SinoNasal Outcome Test (SNOT)-22 score, Nasal Polyp (NP) score, and blood eosinophil count during a 12-month treatment with mepolizumab. Secondary endpoints were to quantify mepolizumab’s effects on the mentioned parameters, identify clinical variables influencing the degree of response to treatment, and portray responder and nonresponder patients. Methods: A multicentric retrospective no-profit observational study on severe asthmatic patients, treated with mepolizumab, and comorbid CRSwNP was conducted. All patients were followed for at least 12 months. SNOT-22 score, NP score, and blood eosinophil count (and other CRS-specific variables) were collected at baseline and after 12 months. Results: Forty-three patients were included. A statistically significant reduction was observed for SNOT-22 score (mean t0 SNOT-22 54.8 ± 25.9; mean t12 SNOT-22 31.5 ± 21.3, p < 0.0001), NP score (median t0 NPS 3 (IQR 3); median t12 NPS 2 (IQR 4), p < 0.0001), and blood eosinophil count (mean t0 blood eosinophils 804.7 ± 461.5 cell/µL; mean t12 blood eosinophils 107.5 ± 104.6 cell/µL, p < 0.0001) after 12 months of treatment. Twenty patients (47%) gained improvement both in clinical and endoscopic outcome. Mepolizumab responder patients presented a t0 SNOT-22 significantly higher than nonresponders (p = 0.0011). Conclusions: Mepolizumab improved CRSwNP outcomes in a population of severe asthmatic patients. No clinical feature emerged to outline the profile of a “typical” responder patient, except for baseline SNOT-22 score, which seemed to affect the response to treatment. Further studies would be necessary to supplement these preliminary evaluations. Full article

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

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15 pages, 3290 KiB

Open AccessEditor’s ChoiceReview

Next-Generation Personalized Medicine: Implementation of Variability Patterns for Overcoming Drug Resistance in Chronic Diseases

by Yaron Ilan

J. Pers. Med. 2022, 12(8), 1303; https://doi.org/10.3390/jpm12081303 - 10 Aug 2022

Cited by 15 | Viewed by 2566

Abstract

Chronic diseases are a significant healthcare problem. Partial or complete non-responsiveness to chronic therapies is a significant obstacle to maintaining the long-term effect of drugs in these patients. A high degree of intra- and inter-patient variability defines pharmacodynamics, drug metabolism, and medication response. [...] Read more.

Chronic diseases are a significant healthcare problem. Partial or complete non-responsiveness to chronic therapies is a significant obstacle to maintaining the long-term effect of drugs in these patients. A high degree of intra- and inter-patient variability defines pharmacodynamics, drug metabolism, and medication response. This variability is associated with partial or complete loss of drug effectiveness. Regular drug dosing schedules do not comply with physiological variability and contribute to resistance to chronic therapies. In this review, we describe a three-phase platform for overcoming drug resistance: introducing irregularity for improving drug response; establishing a deep learning, closed-loop algorithm for generating a personalized pattern of irregularity for overcoming drug resistance; and upscaling the algorithm by implementing quantified personal variability patterns along with other individualized genetic and proteomic-based ways. The closed-loop, dynamic, subject-tailored variability-based machinery can improve the efficacy of existing therapies in patients with chronic diseases. Full article

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14 pages, 938 KiB

Open AccessEditor’s ChoiceReview

Digital Twins in Healthcare: Is It the Beginning of a New Era of Evidence-Based Medicine? A Critical Review

by Patrizio Armeni, Irem Polat, Leonardo Maria De Rossi, Lorenzo Diaferia, Severino Meregalli and Anna Gatti

J. Pers. Med. 2022, 12(8), 1255; https://doi.org/10.3390/jpm12081255 - 30 Jul 2022

Cited by 32 | Viewed by 6913

Abstract

Digital Twins (DTs) are used in many different industries (e.g., manufacturing, construction, automotive, and aerospace), and there is an initial trend of applications in healthcare, mainly focusing on precision medicine. If their potential is fully unfolded, DTs will facilitate the as-yet-unrealized potential of [...] Read more.

Digital Twins (DTs) are used in many different industries (e.g., manufacturing, construction, automotive, and aerospace), and there is an initial trend of applications in healthcare, mainly focusing on precision medicine. If their potential is fully unfolded, DTs will facilitate the as-yet-unrealized potential of connected care and alter the way lifestyle, health, wellness, and chronic disease will be managed in the future. To date, however, due to technical, regulatory and ethical roadblocks, there is no consensus as to what extent DTs in healthcare can introduce revolutionary applications in the next decade. In this review, we present the current applications of DTs covering multiple areas of healthcare (precision medicine, clinical trial design, and hospital operations) to identify the opportunities and the barriers that foster or hinder their larger and faster diffusion. Finally, we discuss the current findings, opportunities and barriers, and provide recommendations to facilitate the continuous development of DTs application in healthcare. Full article

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