Journal of Personalized Medicine

Editorial

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Open AccessEditorial

Personalized and Precision Medicine 2022

by Anne-Marie Caminade

J. Pers. Med. 2023, 13(3), 459; https://doi.org/10.3390/jpm13030459 - 1 Mar 2023

Cited by 1 | Viewed by 1408

Abstract

This Special Issue, “Personalized and Precision Medicine 2022” (https://www [...] Full article

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

Research

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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 4 | Viewed by 2078

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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17 pages, 1626 KiB

Open AccessArticle

DNA Methylation Analysis Reveals Distinct Patterns in Satellite Cell–Derived Myogenic Progenitor Cells of Subjects with Spastic Cerebral Palsy

by Karyn G. Robinson, Adam G. Marsh, Stephanie K. Lee, Jonathan Hicks, Brigette Romero, Mona Batish, Erin L. Crowgey, M. Wade Shrader and Robert E. Akins

J. Pers. Med. 2022, 12(12), 1978; https://doi.org/10.3390/jpm12121978 - 30 Nov 2022

Cited by 2 | Viewed by 2490

Abstract

Spastic type cerebral palsy (CP) is a complex neuromuscular disorder that involves altered skeletal muscle microanatomy and growth, but little is known about the mechanisms contributing to muscle pathophysiology and dysfunction. Traditional genomic approaches have provided limited insight regarding disease onset and severity, [...] Read more.

Spastic type cerebral palsy (CP) is a complex neuromuscular disorder that involves altered skeletal muscle microanatomy and growth, but little is known about the mechanisms contributing to muscle pathophysiology and dysfunction. Traditional genomic approaches have provided limited insight regarding disease onset and severity, but recent epigenomic studies indicate that DNA methylation patterns can be altered in CP. Here, we examined whether a diagnosis of spastic CP is associated with intrinsic DNA methylation differences in myoblasts and myotubes derived from muscle resident stem cell populations (satellite cells; SCs). Twelve subjects were enrolled (6 CP; 6 control) with informed consent/assent. Skeletal muscle biopsies were obtained during orthopedic surgeries, and SCs were isolated and cultured to establish patient–specific myoblast cell lines capable of proliferation and differentiation in culture. DNA methylation analyses indicated significant differences at 525 individual CpG sites in proliferating SC–derived myoblasts (MB) and 1774 CpG sites in differentiating SC–derived myotubes (MT). Of these, 79 CpG sites were common in both culture types. The distribution of differentially methylated 1 Mbp chromosomal segments indicated distinct regional hypo– and hyper–methylation patterns, and significant enrichment of differentially methylated sites on chromosomes 12, 13, 14, 15, 18, and 20. Average methylation load across 2000 bp regions flanking transcriptional start sites was significantly different in 3 genes in MBs, and 10 genes in MTs. SC derived MBs isolated from study participants with spastic CP exhibited fundamental differences in DNA methylation compared to controls at multiple levels of organization that may reveal new targets for studies of mechanisms contributing to muscle dysregulation in spastic CP. Full article

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

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9 pages, 632 KiB

Open AccessArticle

Thromboembolic Events in Patients Undergoing Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer: A Study of Renal Impairment in Relation to Potential Thromboprophylaxis

by Harriet Rydell, Anna Ericson, Victoria Eriksson, Markus Johansson, Johan Svensson, Viqar Banday and Amir Sherif

J. Pers. Med. 2022, 12(12), 1961; https://doi.org/10.3390/jpm12121961 - 27 Nov 2022

Cited by 1 | Viewed by 1410

Abstract

Recent studies on patients with muscle-invasive bladder cancer (MIBC) undergoing neoadjuvant chemotherapy (NAC) have shown an association between NAC and thromboembolic events (TEE) prior to radical cystectomy (RC). Recent studies suggest that central venous access catheters (CVAs) may induce TEEs, and low-molecular-weight heparin [...] Read more.

Recent studies on patients with muscle-invasive bladder cancer (MIBC) undergoing neoadjuvant chemotherapy (NAC) have shown an association between NAC and thromboembolic events (TEE) prior to radical cystectomy (RC). Recent studies suggest that central venous access catheters (CVAs) may induce TEEs, and low-molecular-weight heparin (LMWH) has been mentioned as possible prophylaxis. However, other studies have shown a high incidence of decreased renal function in these patients. The purpose of this study was to determine the portion of MIBC patients with NAC-induced TEEs who had decreased preoperative renal function for whom LMWH potentially would not be beneficial as prophylaxis. We identified 459 cystectomized MIBC patients from two Swedish medical centers from 2009 to 2021. The inclusion criterion of cT2-T4aN0M0 resulted in 220 eligible patients, who were further divided into NAC-administered (n = 187) and NAC-eligible (n = 33), the tentative control group. Values of renal function before, during, and after each NAC cycle were retrospectively collected from individual medical records. Amongst the NAC-administered patients with TEE (n = 29), 41% (95% CI 23.5–61.1%) of patients had decreased renal function. Thus, a substantial portion of NAC-administered patients who developed TEEs had reduced renal function and would have been less likely to have benefited from renal clearance-dependent LMWH prophylaxis. Full article

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

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16 pages, 683 KiB

Open AccessArticle

Psychosocial Impact of Huntington’s Disease and Incentives to Improve Care for Affected Families in the Underserved Region of the Slovak Republic

by Katarína Hubčíková, Tomáš Rakús, Alžbeta Mühlbäck, Ján Benetin, Lucia Bruncvik, Zuzana Petrášová, Jitka Bušková and Martin Brunovský

J. Pers. Med. 2022, 12(12), 1941; https://doi.org/10.3390/jpm12121941 - 22 Nov 2022

Cited by 1 | Viewed by 2294

Abstract

Introduction: Huntington’s disease (HD) is often on the margin of standard medical practice due to its low prevalence, the lack of causal treatment, and the typically long premanifest window prior to the onset of the symptoms, which contrasts with the long-lasting burden that [...] Read more.

Introduction: Huntington’s disease (HD) is often on the margin of standard medical practice due to its low prevalence, the lack of causal treatment, and the typically long premanifest window prior to the onset of the symptoms, which contrasts with the long-lasting burden that the disease causes in affected families. Methods: To capture these socio-psychological aspects of HD and map the experiences of affected individuals, persons at risk of HD, and caregivers, we created a questionnaire using a qualitative research approach. The questionnaire containing 16 questions was conducted online for a period of three months through patient associations in Slovakia and their infrastructures. Results: In total, we received 30 responses. The survey results, in particular, indicate insufficient counselling by physicians with explicitly missing information about the possibility of preimplantation genetic diagnostic. There was also a necessity to improve comprehensive social and health care in the later stages of the disease, raise awareness of the disease in the general health community, and provide more information on ongoing clinical trials. Conclusion: The psychosocial effects, as well as the burden, can be mitigated by comprehensive genetic counselling as well as reproductive and financial guidelines and subsequent therapeutic programs to actively support patients, caregivers, children, and adolescents growing up in affected families, preferably with the help of local HD community association. Limitations: We have used online data collection to reach a wider HD community, but at the same time, we are aware that the quality of the data we would obtain through face-to-face interviews would be considerably better. Therefore, future studies need to be conducted to obtain more detailed information. Full article

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

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7 pages, 430 KiB

Open AccessArticle

Postoperative Inpatient Rehabilitation Does Not Increase Knee Function after Primary Total Knee Arthroplasty

by Dominik Rak, Alexander J. Nedopil, Eric C. Sayre, Bassam A. Masri and Maximilian Rudert

J. Pers. Med. 2022, 12(11), 1934; https://doi.org/10.3390/jpm12111934 - 21 Nov 2022

Cited by 2 | Viewed by 1843

Abstract

Inpatient rehabilitation (IR) is a common postoperative protocol after total knee replacement (TKA). Because IR is expensive and should therefore be justified, this study determined the difference in knee function one year after TKA in patients treated with IR or outpatient rehabilitation, fast-track [...] Read more.

Inpatient rehabilitation (IR) is a common postoperative protocol after total knee replacement (TKA). Because IR is expensive and should therefore be justified, this study determined the difference in knee function one year after TKA in patients treated with IR or outpatient rehabilitation, fast-track rehabilitation (FTR) in particular, which also entails a reduced hospital length of stay. A total of 205 patients were included in this multi-center prospective cohort study. Of the patients, 104 had primary TKA at a German university hospital and received IR, while 101 had primary TKA at a Canadian university hospital and received FTR. Patients receiving IR or FTR were matched by pre-operative demographics and knee function. Oxford Knee Score (OKS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), and EuroQol visual analogue scale (EQ-VAS) determined knee function one year after surgery. Patients receiving IR had a 2.8-point lower improvement in OKS (p = 0.001), a 6.7-point lower improvement in WOMAC (p = 0.063), and a 12.3-point higher improvement in EQ-VAS (p = 0.281) than patients receiving FTR. IR does not provide long-term benefits to patient recovery after primary uncomplicated TKA under the current rehabilitation regime. Full article

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

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16 pages, 3259 KiB

Open AccessArticle

A Pan-Cancer Atlas of Differentially Interacting Hallmarks of Cancer Proteins

by Medi Kori, Gullu Elif Ozdemir, Kazim Yalcin Arga and Raghu Sinha

J. Pers. Med. 2022, 12(11), 1919; https://doi.org/10.3390/jpm12111919 - 17 Nov 2022

Cited by 5 | Viewed by 2156

Abstract

Cancer hallmark genes and proteins orchestrate and drive carcinogenesis to a large extent, therefore, it is important to study these features in different cancer types to understand the process of tumorigenesis and discover measurable indicators. We performed a pan-cancer analysis to map differentially [...] Read more.

Cancer hallmark genes and proteins orchestrate and drive carcinogenesis to a large extent, therefore, it is important to study these features in different cancer types to understand the process of tumorigenesis and discover measurable indicators. We performed a pan-cancer analysis to map differentially interacting hallmarks of cancer proteins (DIHCP). The TCGA transcriptome data associated with 12 common cancers were analyzed and the differential interactome algorithm was applied to determine DIHCPs and DIHCP-centric modules (i.e., DIHCPs and their interacting partners) that exhibit significant changes in their interaction patterns between the tumor and control phenotypes. The diagnostic and prognostic capabilities of the identified modules were assessed to determine the ability of the modules to function as system biomarkers. In addition, the druggability of the prognostic and diagnostic DIHCPs was investigated. As a result, we found a total of 30 DIHCP-centric modules that showed high diagnostic or prognostic performance in any of the 12 cancer types. Furthermore, from the 16 DIHCP-centric modules examined, 29% of these were druggable. Our study presents candidate systems’ biomarkers that may be valuable for understanding the process of tumorigenesis and improving personalized treatment strategies for various cancers, with a focus on their ten hallmark characteristics. Full article

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

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11 pages, 1225 KiB

Open AccessArticle

A Retrospective Analysis of the De Ritis Ratio in Muscle Invasive Bladder Cancer, with Focus on Tumor Response and Long-Term Survival in Patients Receiving Neoadjuvant Chemotherapy and in Chemo Naïve Cystectomy Patients—A Study of a Clinical Multicentre Database

by Victoria Eriksson, Oscar Holmkvist, Ylva Huge, Markus Johansson, Farhood Alamdari, Johan Svensson, Firas Aljabery and Amir Sherif

J. Pers. Med. 2022, 12(11), 1769; https://doi.org/10.3390/jpm12111769 - 27 Oct 2022

Cited by 4 | Viewed by 2060

Abstract

Background: A high pre-treatment De Ritis ratio, the aspartate transaminase/alanine aminotransferase ratio, has been suggested to be of prognostic value for mortality in muscle-invasive bladder cancer (MIBC). Our purpose was to evaluate if a high ratio was associated with mortality and downstaging. Methods: [...] Read more.

Background: A high pre-treatment De Ritis ratio, the aspartate transaminase/alanine aminotransferase ratio, has been suggested to be of prognostic value for mortality in muscle-invasive bladder cancer (MIBC). Our purpose was to evaluate if a high ratio was associated with mortality and downstaging. Methods: A total of 347 Swedish patients with clinically staged T2-T4aN0M0, with administered neoadjuvant chemotherapy (NAC) or eligible for NAC and undergoing radical cystectomy (RC) 2009–2021, were retrospectively evaluated with a low ratio < 1.3 vs. high ratio > 1.3, by Log Rank test, Cox regression and Mann–Whitney U-test (MWU), SPSS 27. Results: Patients with a high ratio had a decrease of up to 3 years in disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS) (p = 0.009, p = 0.004 and p = 0.009) and 5 years in CSS and OS (p = 0.019 and p = 0.046). A high ratio was associated with increased risk of mortality, highest in DFS (HR, 1.909; 95% CI, 1.265–2.880; p = 0.002). No significant relationship between downstaging and a high ratio existed (p = 0.564 MWU). Conclusion: A high pre-treatment De Ritis ratio is on a population level, associated with increased mortality post-RC in endpoints DFS, CSS and OS. Associations decrease over time and require further investigations to determine how strong the associations are as meaningful prognostic markers for long-term mortality in MIBC. The ratio is not suitable for downstaging-prediction. Full article

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

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10 pages, 379 KiB

Open AccessArticle

Vitamin D Levels in Patients with Overlap Syndrome, Is It Associated with Disease Severity?

by Kostas Archontogeorgis, Athanasios Voulgaris, Evangelia Nena, Athanasios Zissimopoulos, Izolde Bouloukaki, Sophia E. Schiza and Paschalis Steiropoulos

J. Pers. Med. 2022, 12(10), 1693; https://doi.org/10.3390/jpm12101693 - 11 Oct 2022

Cited by 4 | Viewed by 1619

Abstract

Background: The coexistence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) has been defined as overlap syndrome (OVS). Recently, a link between OSA, COPD and Vitamin D (Vit D) serum concentration was reported, however, evidence regarding Vit D status in [...] Read more.

Background: The coexistence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) has been defined as overlap syndrome (OVS). Recently, a link between OSA, COPD and Vitamin D (Vit D) serum concentration was reported, however, evidence regarding Vit D status in patients with OVS is scarce. The aim of the present study was to evaluate Vit D serum levels and to explore the association of those levels with anthropometric, pulmonary function and sleep parameters in patients with OVS. Methods: Vit D serum levels were measured in patients diagnosed with OVS, as confirmed by overnight polysomnography and pulmonary function testing. Results: A total of 90 patients (79 males and 11 females) were included in the analysis. The patients were divided into three groups matched for age, gender, and BMI: the control group that included 30 patients (27 males and 3 females), the OSA group that included 30 patients (26 males and 4 females), and the OVS group that included 30 patients (26 males and 4 females). Patients with OVS exhibited decreased serum 25(OH)D levels compared with OSA patients and controls (14.5 vs. 18.6 vs. 21.6 ng/mL, p < 0.001). In the OVS group, multiple linear regression analysis identified AHI and FEV₁, as predictors of serum 25(OH)D levels (p = 0.041 and p = 0.038, respectively). Conclusions: Lower Vit D levels have been observed in patients with OVS compared with OSA patients and non-apneic controls, indicating an increased risk of hypovitaminosis D in this population which might be associated with disease severity. Full article

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

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14 pages, 1724 KiB

Open AccessArticle

The Effect of Lumbar Belts with Different Extensibilities on Kinematic, Kinetic, and Muscle Activity of Sit-to-Stand Motions in Patients with Nonspecific Low Back Pain

by Sang-Cheol Im, Seong-Wook Seo, Na-Yeon Kang, Hoon Jo and Kyoung Kim

J. Pers. Med. 2022, 12(10), 1678; https://doi.org/10.3390/jpm12101678 - 9 Oct 2022

Cited by 4 | Viewed by 2356

Abstract

Although lumbar belts can be used for the treatment and prevention of low back pain, the role of the lumbar belt remains unclear without clear guidelines. This study aimed to investigate the effect of lumbar belts with different extensibilities on the kinematics, kinetics, [...] Read more.

Although lumbar belts can be used for the treatment and prevention of low back pain, the role of the lumbar belt remains unclear without clear guidelines. This study aimed to investigate the effect of lumbar belts with different extensibilities on the kinematics, kinetics, and muscle activity of sit-to-stand motions in terms of motor control in patients with nonspecific low back pain. A total of 30 subjects participated in the study: 15 patients with nonspecific low back pain and 15 healthy adults. Participants performed the sit-to-stand motion in random order of three conditions: no lumbar belt, wearing an extensible lumbar belt, and wearing a non-extensible lumbar belt. The sit-to-stand motion’s kinematic, kinetic, and muscle activity variables in each condition were measured using a three-dimensional motion analysis device, force plate, and surface electromyography. An interaction effect was found for the time taken, anterior pelvic tilt angle, and muscle activity of the vastus lateralis and biceps femoris. The two lumbar belts with different extensibilities had a positive effect on motor control in patients with nonspecific low back pain. Therefore, both types of extensible lumbar belts can be useful in the sit-to-stand motion, which is an important functional activity for patients with nonspecific low back pain. Full article

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

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12 pages, 2976 KiB

Open AccessFeature PaperArticle

Diagnostic Efficacy of Ultra-Short Term HRV Analysis in Obstructive Sleep Apnea

by Seung-Su Ha and Dong-Kyu Kim

J. Pers. Med. 2022, 12(9), 1494; https://doi.org/10.3390/jpm12091494 - 13 Sep 2022

Cited by 3 | Viewed by 2649

Abstract

Heart rate variability (HRV) is the standard method for assessing autonomic nervous system (ANS) activity and is considered a surrogate marker for sympathetic overactivity in obstructive sleep apnea (OSA). Although HRV features are usually obtained from the short-term segment method, it is impossible [...] Read more.

Heart rate variability (HRV) is the standard method for assessing autonomic nervous system (ANS) activity and is considered a surrogate marker for sympathetic overactivity in obstructive sleep apnea (OSA). Although HRV features are usually obtained from the short-term segment method, it is impossible to evaluate rapid dynamic changes in ANS activity. Herein, we propose the ultra-short-term analysis to detect the balance of ANS activity in patients with OSA. In 1021 OSA patients, 10 min HRV target datasets were extracted from polysomnographic data and analyzed by shifting the 2 min (ultra-short-term) and 5 min (short-term) segments. We detected frequency-domain parameters, including total power (Ln TP), very low frequency (Ln VLF), low frequency (Ln LF), and high frequency (Ln HF). We found that overall HRV feature alterations indicated sympathetic overactivity dependent on OSA severity, and that this was more pronounced in the ultra-short-term methodology. The apnea-hypopnea index, oxygen desaturation index, and Epworth sleepiness scale correlated with increased sympathetic activity and decreased parasympathetic activity, regardless of the methodology. The Bland-Altman plot analyses also showed a higher agreement of HRV features between the two methodologies. This study suggests that ultra-short-term HRV analysis may be a useful method for detecting alterations in ANS function in OSA patients. Full article

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

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16 pages, 3422 KiB

Open AccessArticle

Short- and Long-Term Effects of a Prebiotic Intervention with Polyphenols Extracted from European Black Elderberry—Sustained Expansion of Akkermansia spp.

by Simon Reider, Christina Watschinger, Julia Längle, Ulrike Pachmann, Nicole Przysiecki, Alexandra Pfister, Andreas Zollner, Herbert Tilg, Stephan Plattner and Alexander R. Moschen

J. Pers. Med. 2022, 12(9), 1479; https://doi.org/10.3390/jpm12091479 - 9 Sep 2022

Cited by 12 | Viewed by 5160

Abstract

(1) Background: The intestinal microbiome has emerged as a central factor in human physiology and its alteration has been associated with disease. Therefore, great hopes are placed in microbiota-modulating strategies. Among various approaches, prebiotics, substrates with selective metabolization conferring a health benefit to [...] Read more.

(1) Background: The intestinal microbiome has emerged as a central factor in human physiology and its alteration has been associated with disease. Therefore, great hopes are placed in microbiota-modulating strategies. Among various approaches, prebiotics, substrates with selective metabolization conferring a health benefit to the host, are promising candidates. Herein, we studied the prebiotic properties of a purified extract from European black elderberries, with a high and standardized content of polyphenols and anthocyanins. (2) Methods: The ELDERGUT trial represents a 9-week longitudinal intervention study divided into 3 distinct phases, namely a baseline, an intervention and a washout period, three weeks each. The intervention consisted of capsules containing 300 mg elderberry extract taken twice a day. Patient-reported outcomes and biosamples were collected weekly. Microbiome composition was assessed using 16S amplicon metagenomics. (3) Results: The supplementation was well tolerated. Microbiome trajectories were highly individualized with a profound shift in diversity indices immediately upon initiation and after termination of the compound. This was accompanied by corresponding changes in species abundance over time. Of particular interest, the relative abundance of Akkermansia spp. continued to increase in a subset of participants even beyond the supplementation period. Associations with participant metadata were detected. Full article

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

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10 pages, 977 KiB

Open AccessArticle

Thiopurine S-Methyltransferase Polymorphisms Predict Hepatotoxicity in Azathioprine-Treated Patients with Autoimmune Diseases

by Heh-Shiang Sheu, Yi-Ming Chen, Yi-Ju Liao, Chia-Yi Wei, Jun-Peng Chen, Hsueh-Ju Lin, Wei-Ting Hung, Wen-Nan Huang and Yi-Hsing Chen

J. Pers. Med. 2022, 12(9), 1399; https://doi.org/10.3390/jpm12091399 - 28 Aug 2022

Cited by 4 | Viewed by 2544

Abstract

Thiopurine methyltransferase (TPMT) is the rate-limiting enzyme in Azathioprine (AZA) metabolization. Although studies have discussed the association between the TPMT polymorphisms and myelosuppression, the data about the relationship between TPMT genotypes and hepatoxicity in Asian patients remain limited. This study investigated the correlation [...] Read more.

Thiopurine methyltransferase (TPMT) is the rate-limiting enzyme in Azathioprine (AZA) metabolization. Although studies have discussed the association between the TPMT polymorphisms and myelosuppression, the data about the relationship between TPMT genotypes and hepatoxicity in Asian patients remain limited. This study investigated the correlation between TPMT polymorphisms and AZA-related hepatotoxicity. This study enrolled the patients who had prior exposure to AZA from the Taichung Veterans General Hospital (TCVGH)-Taiwan Precision Medicine Initiative (TPMI) cohort. Genetic variants were determined using a single nucleotide polymorphism (SNP) array. Participants were accordingly categorized into normal metabolizer (NM) and non-normal metabolizer (non-NM) groups. From the TCVGH-TPMI cohort, we included 50 TPMT non-NM patients, including 1 poor metabolizer (PM), 49 intermediate metabolizers (IMs), and 1000 NM patients. The non-NM genotype was associated with hepatotoxicity compared with the NM genotype (hazard ratio (HR): 3.85, 95% confidence interval (CI): 1.83–8.10). In the non-NM group, the 3-year cumulative incidence of hepatotoxicity was higher than that in the NM group at 8.5% in the first year and 18.6% in the second and third years (p < 0.001). A TPMT non-NM genotype was associated with the occurrence of hepatotoxicity following AZA therapy. Preemptive testing helps individualize AZA therapy by minimizing the risk of hepatotoxicity. Full article

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

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11 pages, 3515 KiB

Open AccessArticle

Individualized 3D-Printed Bone-Anchored Maxillary Protraction Device for Growth Modification in Skeletal Class III Malocclusion

by Minji Kim, Jingwen Li, Sehyang Kim, Wonho Kim, Sun-Hyun Kim, Sung-Min Lee, Young Long Park, Sook Yang and Jin-Woo Kim

J. Pers. Med. 2021, 11(11), 1087; https://doi.org/10.3390/jpm11111087 - 26 Oct 2021

Cited by 6 | Viewed by 3281

Abstract

Bone-anchored maxillary protraction (BAMP) is effective for skeletal Class III malocclusion. However, infection, screw and plate loosening, and device failures occur with conventional plates. This pilot prospective study analyzed the feasibility of individualized BAMP using preoperative simulation and 3D titanium printing in patients [...] Read more.

Bone-anchored maxillary protraction (BAMP) is effective for skeletal Class III malocclusion. However, infection, screw and plate loosening, and device failures occur with conventional plates. This pilot prospective study analyzed the feasibility of individualized BAMP using preoperative simulation and 3D titanium printing in patients referred by the orthodontic department for four BAMP miniplates. Preoperative cone beam computed tomography data were analyzed using CAD/CAM software to fabricate the individualized 3D-printed BAMP device. The customized plates were printed using selective laser sintering and inserted onto the bone through an adjunct transfer jig. The accuracy of preoperative simulation and actual placement of the BAMP device were tested by superimposing simulated positioned digital images and postoperative computed tomography data. The growth modification effect depended on superimposition of lateral cephalograms and comparative changes in SNA, SNB, ANB, and Wits. Two male patients were finally included in the study. BAMP decreased the ANB difference (−4.56 to −1.09) and Wits appraisal (−7.52 to −3.26) after 2 years. Normal measurement indices for sagittal and vertical growth indicated successful growth modification. The mean accuracy between preoperative simulation and actual surgery was 0.1081 ± 0.5074 mm. This treatment modality involving preoperative simulation and 3D titanium printing for fabricating and placing customized BAMP devices precisely at planned locations is effective for treating skeletal Class III malocclusion. Full article

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

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11 pages, 1363 KiB

Open AccessArticle

Risk Factors of 30-Day All-Cause Mortality in Patients with Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infection

by Keh-Sen Liu, Yao-Shen Tong, Ming-Tsung Lee, Hung-Yu Lin and Min-Chi Lu

J. Pers. Med. 2021, 11(7), 616; https://doi.org/10.3390/jpm11070616 - 29 Jun 2021

Cited by 15 | Viewed by 2590

Abstract

An optimal antimicrobial regimen for the treatment of patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection (BSI) is currently unavailable. This study aimed to identify the appropriate antibiotics and the risk factors of all-cause mortality for CRKP BSI patients. This retrospective cohort study [...] Read more.

An optimal antimicrobial regimen for the treatment of patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection (BSI) is currently unavailable. This study aimed to identify the appropriate antibiotics and the risk factors of all-cause mortality for CRKP BSI patients. This retrospective cohort study included the hospitalized patients with CRKP BSI. Primary outcome was 30-day all-cause mortality. Cox regression analysis was used to evaluate the risk factors of 30-day mortality. A total of 89 patients were included with a 30-day mortality of 52.1%. A total of 52 (58.4%) patients were treated with appropriate antimicrobial regimens and 58 (65.2%) isolates carried bla_KPC-2 genes. Microbiologic eradication within 7 days (adjusted hazard ratio [HR] = 0.09, p < 0.001), platelet count (per 1 × 10⁴/mm³, adjusted HR = 0.95, p = 0.002), and Pitt bacteremia scores (adjusted HR = 1.40, p < 0.001) were independently associated with 30-day all-cause mortality. No effective antimicrobial regimens were identified. In conclusion, risk factors of 30-day mortality in patients with CRKP BSI included microbiologic eradication > 7 days, lower platelet count, and a higher Pitt bacteremia score. These findings render a new insight into the clinical landscape of CRKP BSI. Full article

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

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12 pages, 1143 KiB

Open AccessArticle

Dynamic Collaborations for the Development of Immune Checkpoint Blockade Agents

by Arisa Djurian, Tomohiro Makino, Yeongjoo Lim, Shintaro Sengoku and Kota Kodama

J. Pers. Med. 2021, 11(6), 460; https://doi.org/10.3390/jpm11060460 - 24 May 2021

Cited by 5 | Viewed by 3587

Abstract

We studied the overview of drug discovery and development to understand the recent trends and potential success factors of interorganizational collaboration by reviewing 1204 transactions performed until 2019 for 107 anticancer drugs approved by the US Food and Drug Administration (FDA) from 1999 [...] Read more.

We studied the overview of drug discovery and development to understand the recent trends and potential success factors of interorganizational collaboration by reviewing 1204 transactions performed until 2019 for 107 anticancer drugs approved by the US Food and Drug Administration (FDA) from 1999 to 2018. Immune checkpoint blockade was found to be a significantly active area in interorganizational transactions, especially the number of alliances, compared with other mechanisms of action of small molecules and biologics for cancer treatment. Furthermore, the analysis of pembrolizumab and nivolumab showed that the number of approved indications for these two drugs has been rapidly expanding since their first approval in 2014. Examination of the acquisitions and alliances regarding pembrolizumab and nivolumab showed that many combination partners were developed by US-based biotechnology or start-up companies, the majority of which were biologics. These findings suggest that immune checkpoint blockade is a paradigm for cancer treatment, resulting in huge product sales and continuous indication expansion. Additionally, interorganizational collaboration, especially trial collaboration, is a strategic approach for the development of immune checkpoint blockade agents. The translation of these empirical practices to new drug candidates is expected for the research and development of innovative drugs in the future. Full article

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

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12 pages, 302 KiB

Open AccessReview

Multiple Sclerosis and Autoimmune Comorbidities

by Viviana Nociti and Marina Romozzi

J. Pers. Med. 2022, 12(11), 1828; https://doi.org/10.3390/jpm12111828 - 3 Nov 2022

Cited by 12 | Viewed by 3311

Abstract

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system characterized by broad inter- and intraindividual heterogeneity and different prognoses. Multisystem comorbidities are frequent features in people with MS (PwMS) and can affect treatment choices, quality of life, [...] Read more.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system characterized by broad inter- and intraindividual heterogeneity and different prognoses. Multisystem comorbidities are frequent features in people with MS (PwMS) and can affect treatment choices, quality of life, disability and mortality. In this scenario, autoimmune comorbidities play a cardinal role for several reasons, such as the implication on MS pathogenesis, diagnostic delay, disease activity, disability progression, brain atrophy, and treatment choice. However, the impact of an autoimmune comorbid condition on MS is not fully elucidated. This review aims to summarize the currently available data on the incidence and prevalence of autoimmune diseases in PwMS, the possible effect of this association on clinical and neuroradiological MS course and its impact on treatment choice. Full article

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

11 pages, 3853 KiB

Open AccessReview

Clinical Application of Ultra-High-Frequency Ultrasound

by Anna Russo, Alfonso Reginelli, Giorgia Viola Lacasella, Enrico Grassi, Michele Ahmed Antonio Karaboue, Tiziana Quarto, Gian Maria Busetto, Alberto Aliprandi, Roberta Grassi and Daniela Berritto

J. Pers. Med. 2022, 12(10), 1733; https://doi.org/10.3390/jpm12101733 - 19 Oct 2022

Cited by 21 | Viewed by 3554

Abstract

Musculoskeletal ultrasound involves the study of many superficial targets, especially in the hands, wrists, and feet. Many of these areas are within the first 3 cm of the skin surface and are ideal targets for ultra-high-frequency ultrasound. The high spatial resolution and the [...] Read more.

Musculoskeletal ultrasound involves the study of many superficial targets, especially in the hands, wrists, and feet. Many of these areas are within the first 3 cm of the skin surface and are ideal targets for ultra-high-frequency ultrasound. The high spatial resolution and the superb image quality achievable allow foreseeing a wider use of this novel technique, which has the potential to bring innovation to diagnostic imaging. Full article

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

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19 pages, 335 KiB

Open AccessFeature PaperReview

Non-Oncological Radiotherapy: A Review of Modern Approaches

by Valerio Nardone, Emma D’Ippolito, Roberta Grassi, Angelo Sangiovanni, Federico Gagliardi, Giuseppina De Marco, Vittorio Salvatore Menditti, Luca D’Ambrosio, Fabrizio Cioce, Luca Boldrini, Viola Salvestrini, Carlo Greco, Isacco Desideri, Francesca De Felice, Ida D’Onofrio, Roberto Grassi, Alfonso Reginelli and Salvatore Cappabianca

J. Pers. Med. 2022, 12(10), 1677; https://doi.org/10.3390/jpm12101677 - 9 Oct 2022

Cited by 5 | Viewed by 3644

Abstract

Despite being usually delivered in oncological patients, radiotherapy can be used as a successful treatment for several non-malignant disorders. Even though this use of radiotherapy has been scarcely investigated since the 1950s, more recent interest has actually shed the light on this approach. [...] Read more.

Despite being usually delivered in oncological patients, radiotherapy can be used as a successful treatment for several non-malignant disorders. Even though this use of radiotherapy has been scarcely investigated since the 1950s, more recent interest has actually shed the light on this approach. Thus, the aim of this narrative review is to analyze the applications of non-oncological radiotherapy in different disorders. Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. This review contains a narrative report and a critical discussion of non-oncological radiotherapy approaches. In conclusion, non-oncological radiotherapy is a safe and efficacious approach to treat several disorders that needs to be further investigated and used in clinical practice. Full article

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

12 pages, 2094 KiB

Open AccessFeature PaperReview

Dendrimers, an Emerging Opportunity in Personalized Medicine?

by Anne-Marie Caminade

J. Pers. Med. 2022, 12(8), 1334; https://doi.org/10.3390/jpm12081334 - 19 Aug 2022

Cited by 38 | Viewed by 4737

Abstract

Dendrimers are highly branched macromolecules tailorable at will to fulfil precise requirements. They have generated a great many expectations and a huge number of publications and patents in relation to medicine, including in relation to personalized medicine, but have resulted in very poor [...] Read more.

Dendrimers are highly branched macromolecules tailorable at will to fulfil precise requirements. They have generated a great many expectations and a huge number of publications and patents in relation to medicine, including in relation to personalized medicine, but have resulted in very poor clinical translation up to now. As clinical trials are the first steps in view of developing new compounds for (a personalized) medicine, this review focusses on the clinical trials carried out with dendrimers. Many of these clinical trials have been recently posted (2020–2022); thus, only very few concern phase 3. The safety and efficiency of essentially two main types of dendrimers, based on polylysine and polyamidoamide scaffolds, have been assessed up to now. These dendrimers were tested with the aim of treating mainly bacterial vaginosis, cancers, and COVID-19. Full article

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

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15 pages, 707 KiB

Open AccessFeature PaperReview

COVID-19, Mucormycosis and Cancer: The Triple Threat—Hypothesis or Reality?

by Ishika Mahajan, Aruni Ghose, Deepika Gupta, Manasi Manasvi, Saisha Bhandari, Aparimita Das, Elisabet Sanchez and Stergios Boussios

J. Pers. Med. 2022, 12(7), 1119; https://doi.org/10.3390/jpm12071119 - 10 Jul 2022

Cited by 6 | Viewed by 2244

Abstract

COVID-19 has been responsible for widespread morbidity and mortality worldwide. Invasive mucormycosis has death rates scaling 80%. India, one of the countries hit worst by the pandemic, is also a hotbed with the highest death rates for mucormycosis. Cancer, a ubiquitously present menace, [...] Read more.

COVID-19 has been responsible for widespread morbidity and mortality worldwide. Invasive mucormycosis has death rates scaling 80%. India, one of the countries hit worst by the pandemic, is also a hotbed with the highest death rates for mucormycosis. Cancer, a ubiquitously present menace, also contributes to higher case fatality rates. All three entities studied here are individual, massive healthcare threats. The danger of one disease predisposing to the other, the poor performance status of patients with all three diseases, the impact of therapeutics for one disease on the pathology and therapy of the others all warrant physicians having a better understanding of the interplay. This is imperative so as to effectively establish control over the individual patient and population health. It is important to understand the interactions to effectively manage all three entities together to reduce overall morbidity. In this review article, we search for an inter-relationship between the COVID-19 pandemic, emerging mucormycosis, and the global giant, cancer. Full article

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

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