Journal of Personalized Medicine

14 pages, 1523 KiB

Open AccessArticle

From Croatian Roma to 1000 Genomes: The Story of the CYP2D6 Gene Promoter and Enhancer SNPs

by Anita Stojanović Marković, Željka Celinšćak, Maja Šetinc, Tatjana Škarić-Jurić, Marijana Peričić Salihović and Matea Zajc Petranović

J. Pers. Med. 2022, 12(8), 1353; https://doi.org/10.3390/jpm12081353 - 22 Aug 2022

Viewed by 1770

Abstract

The CYP2D6 gene encodes an enzyme responsible for the metabolism of ~20% of clinically prescribed drugs. In this study, 18 SNPs from the enhancer and promoter regions of CYP2D6 in 323 Roma from Croatia were genotyped, to find out whether the demographic history [...] Read more.

The CYP2D6 gene encodes an enzyme responsible for the metabolism of ~20% of clinically prescribed drugs. In this study, 18 SNPs from the enhancer and promoter regions of CYP2D6 in 323 Roma from Croatia were genotyped, to find out whether the demographic history of Roma affected the distribution of the studied SNPs and their linkage disequilibrium (LD) values, with the major SNPs defining the CYP2D6 star alleles. No differences were found between the three Roma groups in allele and genotype frequencies. The distribution of LD values of Roma was compared with LD values of European and Asian populations. Regulatory CYP2D6 SNPs (rs5758550, rs28624811, rs1080985 and rs1080983) showed similar distribution and the highest LDs with rs16947 from the gene-coding region in all populations. In the promoter region, a complete LD between rs1080989 and rs28588594, and between rs1080983 and rs28624811, was found in Croatian Roma and investigated populations from 1000 genomes. A high LD was also found between rs1080985 from the promoter and rs5758550 from the enhancer region. SNP rs28735595 from the gene promoter region had the highest LD, with two gene region SNPs, rs1058164 and rs1135840. To conclude, the Croatian Roma population shows an LD pattern of the CYP2D6 gene region similar to the 1000 Genomes European and Asian populations. Full article

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

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10 pages, 983 KiB

Open AccessArticle

Femoral Pulse Pressure Variation Is Not Interchangeable with Radial Pulse Pressure Variation during Living Donor Liver Transplantation

by Doyeon Kim, Jin Hee Ahn, Sangbin Han, Justin Sangwook Ko, Mi Sook Gwak and Gaab Soo Kim

J. Pers. Med. 2022, 12(8), 1352; https://doi.org/10.3390/jpm12081352 - 22 Aug 2022

Cited by 2 | Viewed by 1603

Abstract

The radial artery is commonly used as the site measuring pulse pressure variation (PPV) during surgery. Accurate measurement of circulating blood volume and timely interventions to maintain optimal circulating blood volume is important to deliver sufficient oxygen to tissues and organs. It has [...] Read more.

The radial artery is commonly used as the site measuring pulse pressure variation (PPV) during surgery. Accurate measurement of circulating blood volume and timely interventions to maintain optimal circulating blood volume is important to deliver sufficient oxygen to tissues and organs. It has not rather than never studied in patients undergoing liver transplantation whether PPV measured at peripheral sites, such as the radial artery, do represent central PPV for evaluating blood volume. In this retrospective study, 51 liver transplant recipients were enrolled. The two PPVs had been automatically recorded every minute in electrical medical records. A total 1878 pairs of the two PPVs were collected. The interchangeability of PPV measured at the radial and the femoral artery was analyzed by using the Bland–Altman plot, four-quadrant plot, Cohen’s kappa (k), and receiver operating curve. The bias and limits of agreement of the two PPVs were −1.3% and −8.8% to 6.2%, respectively. The percentage error was 75%. The concordance rate was 65%. The Kappa of PPV-radial determining whether PPV-femoral was >13% or ≤13% was 0.64. We found that PPV-radial is not interchangeable with PPV-femoral during liver transplantation. Additionally, PPV-radial failed to reliably track changes of PPV-femoral. Lastly, the clinical decision regarding blood volume status (depletion or not) is significantly different between the two PPVs. Therefore, PPV-femoral may help maintain blood volume circulating to major organs including the newly transplanted liver graft for liver transplant recipients. Full article

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18 pages, 351 KiB

Open AccessReview

Postoperative Intensive Care Management of Aortic Repair

by Stefano De Paulis, Gabriella Arlotta, Maria Calabrese, Filippo Corsi, Temistocle Taccheri, Maria Enrica Antoniucci, Lorenzo Martinelli, Francesca Bevilacqua, Giovanni Tinelli and Franco Cavaliere

J. Pers. Med. 2022, 12(8), 1351; https://doi.org/10.3390/jpm12081351 - 22 Aug 2022

Cited by 7 | Viewed by 3512

Abstract

Vascular surgery patients have multiple comorbidities and are at high risk for perioperative complications. Aortic repair surgery has greatly evolved in recent years, with an increasing predominance of endovascular techniques (EVAR). The incidence of cardiac complications is significantly reduced with endovascular repair, but [...] Read more.

Vascular surgery patients have multiple comorbidities and are at high risk for perioperative complications. Aortic repair surgery has greatly evolved in recent years, with an increasing predominance of endovascular techniques (EVAR). The incidence of cardiac complications is significantly reduced with endovascular repair, but high-risk patients require postoperative ST-segment monitoring. Open aortic repair may portend a prohibitive risk of respiratory complications that could be a contraindication for surgery. This risk is greatly reduced in the case of an endovascular approach, and general anesthesia should be avoided whenever possible in the case of endovascular repair. Preoperative renal function and postoperative kidney injury are powerful determinants of short- and long-term outcome, so that preoperative risk stratification and secondary prevention are critical tasks. Intraoperative renal protection with selective renal and distal aortic perfusion is essential during open repair. EVAR has lower rates of postoperative renal failure compared to open repair, with approximately half the risk for acute kidney injury (AKI) and one-third of the risk of hemodialysis requirement. Spinal cord ischemia used to be the most distinctive and feared complication of aortic repair. The risk has significantly decreased since the beginning of aortic surgery, with advances in surgical technique and spinal protection protocols, and is lower with endovascular repair. Endovascular repair avoids extensive aortic dissection and aortic cross-clamping and is generally associated with reduced blood loss and less coagulopathy. The intensive care physician must be aware that aortic repair surgery has an impact on every organ system, and the importance of early recognition of organ failure cannot be overemphasized. Full article

10 pages, 1551 KiB

Open AccessArticle

Potential Markers to Reduce Non-Contrast Computed Tomography Use for Symptomatic Patients with Suspected Ureterolithiasis

by Yuval Avda, Igal Shpunt, Jonathan Modai, Dan Leibovici, Brian Berkowitz and Yaniv Shilo

J. Pers. Med. 2022, 12(8), 1350; https://doi.org/10.3390/jpm12081350 - 21 Aug 2022

Viewed by 1809

Abstract

Most patients with ureterolithiasis are managed successfully with conservative treatment. In this context, delineation of clinical risk factors that identify patients with low risk for surgical intervention may reduce use of Non-Contrast Computed Tomography (NCCT). Here, emergency department patient files from a 14-month [...] Read more.

Most patients with ureterolithiasis are managed successfully with conservative treatment. In this context, delineation of clinical risk factors that identify patients with low risk for surgical intervention may reduce use of Non-Contrast Computed Tomography (NCCT). Here, emergency department patient files from a 14-month period were reviewed retrospectively, to identify patients who underwent NCCT and showed a ureteral stone. Demographic, clinical and laboratory information was collected. Patients were grouped to either requiring surgical intervention (Group 1) or having successful conservative management (Group 2). The cohort included 368 patients; 36.1% ultimately required surgical intervention (Group 1) and 63.9% were successfully treated conservatively (Group 2). On univariate analysis, patients who required surgical intervention were older, had longer duration of symptoms, had history of urolithiasis and surgical intervention for urolithiasis and had higher serum creatinine levels. Multivariate analysis identified the following risk factors associated with surgical intervention: creatinine >1.5 mg/dL, duration of symptoms ≥ 1.5 days and age > 45 years. Patients with 0, 1, 2 or 3 of the identified risk factors had 19%, 32%, 53% and 73% likelihood, respectively, of surgical intervention. Incorporating these data may reduce the use of NCCT scans in patients who are likely to pass a stone via conservative management. Full article

(This article belongs to the Special Issue Advancements in Minimally Invasive Urological Surgery and Endourology)

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11 pages, 1722 KiB

Open AccessArticle

The Efficacy of DW and T1-W MRI Combined with CT in the Preoperative Evaluation of Cholesteatoma

by Wan-Hsuan Sun, Jiun-Kai Fan and Tzu-Chin Huang

J. Pers. Med. 2022, 12(8), 1349; https://doi.org/10.3390/jpm12081349 - 21 Aug 2022

Cited by 4 | Viewed by 2932

Abstract

Objective: This study aims to assess the efficacy of diffusion-weighted (DW) and T1-weighted (T1W) magnetic resonance imaging (MRI) combined with high-resolution computed tomography (HRCT) (together as DW-T1W-CT) in the preoperative evaluation of the presence and extent of cholesteatoma, which helps determine whether a [...] Read more.

Objective: This study aims to assess the efficacy of diffusion-weighted (DW) and T1-weighted (T1W) magnetic resonance imaging (MRI) combined with high-resolution computed tomography (HRCT) (together as DW-T1W-CT) in the preoperative evaluation of the presence and extent of cholesteatoma, which helps determine whether a patient is suitable for transcanal endoscopic ear surgery (TEES). Methods: This retrospective study included 35 patients (18 male and 17 female) aged from 2 to 81 years diagnosed with chronic otitis media with or without cholesteatoma, who had received surgical treatment and a preoperative MRI and HRCT during the period of December 2015 to December 2020 at Cathay General Hospital. We compared the preoperative DW-T1W-CT findings with the intraoperative findings and final pathologic diagnosis. The accurate predictive value was evaluated using the presence of cholesteatoma and its extent. Results: Regarding the efficacy of detecting cholesteatoma, we found a sensitivity of 92% (23/25 cases with cholesteatoma), a specificity of 90% (9/10 cases without cholesteatoma), and an overall accurate predictive value of 91.4% (32/35) by using combined DW-T1W-CT imaging. With regard to evaluating the extent of cholesteatoma, the combined DW-T1W-CT images obtained an accurate predictive value of 84% (21/25 cases of cholesteatoma). Conclusion: Combined DW-T1W-CT has been proven to be a reliable tool in detecting the presence of cholesteatoma. It is also useful in preoperatively depicting the extent of cholesteatoma, which is crucial for determining whether a patient is suitable for TEES, aiding in surgical planning and patient consultation. Full article

(This article belongs to the Special Issue Frontiers in Pathogenesis and Therapeutics of Cancer)

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12 pages, 1524 KiB

Open AccessArticle

Clinical Pharmacists’ Knowledge of and Attitudes toward Pharmacogenomic Testing in China

by Xiaoyan Nie, Tong Jia, Xiaowen Hu, Sicong Li, Xinyi Zhang, Caiying Wu, Yuqing Zhang, Jing Chen, Luwen Shi and Christine Y. Lu

J. Pers. Med. 2022, 12(8), 1348; https://doi.org/10.3390/jpm12081348 - 21 Aug 2022

Cited by 3 | Viewed by 2102

Abstract

(1) Background: Uptake of pharmacogenomic testing in routine clinical practices is currently slow in China. Pharmacists might play an important role in leveraging care through applying pharmacogenomics, therefore, it is important to better understand clinical pharmacists’ knowledge of and attitudes toward pharmacogenomic testing, [...] Read more.

(1) Background: Uptake of pharmacogenomic testing in routine clinical practices is currently slow in China. Pharmacists might play an important role in leveraging care through applying pharmacogenomics, therefore, it is important to better understand clinical pharmacists’ knowledge of and attitudes toward pharmacogenomic testing, which has not been well-studied. (2) Methods: A self-administered survey was developed based on previous knowledge of pharmacogenomic testing and its uptake in China. Participants were recruited through the Committee of Pharmaceutical Affairs Management under the Chinese Hospital Association. (3) Results: A total of 1005 clinical pharmacists completed the questionnaire, among whom 996 (99.10%) had heard of pharmacogenomic testing before participation. More than half of respondents (60.0%, n = 597) rated their knowledge of pharmacogenomic testing as “average”, while 25% rated it “good” or “excellent”. “Guidelines, consensus and treatment paths for disease diagnosis and treatment” (78.7%) were the most preferred sources of information about pharmacogenomic testing. Most respondents (77.0%) believed that pharmacogenomics could “help to improve efficacy and reduce the incidence of adverse reactions”. Our participants also believed that patients would benefit most from pharmacogenomic testing through better prediction of individual drug responses and thus informed treatment decisions. The top challenge for the uptake of pharmacogenomic testing was its high cost or lack of insurance coverage (76.7%). (4) Conclusions: Most Chinese clinical pharmacists who participated in our study had a positive attitude toward pharmacogenomic testing, while the knowledge of pharmacogenomic testing was generally self-assessed as average. Full article

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11 pages, 646 KiB

Open AccessReview

Endotyping of Cholesteatoma: Which Molecular Biomarkers? A Systematic Review

by Elena Cantone, Claudio Di Nola, Eugenio De Corso, Michele Cavaliere, Giusi Grimaldi, Anna Rita Fetoni and Gaetano Motta

J. Pers. Med. 2022, 12(8), 1347; https://doi.org/10.3390/jpm12081347 - 21 Aug 2022

Cited by 1 | Viewed by 2091

Abstract

Background: So far, no medical treatment is available for cholesteatoma (C) and the only effective therapy is complete surgical removal, but recurrence is common even after surgical treatment. While C is classically divided into two clinical phenotypes, congenital and acquired, only a few [...] Read more.

Background: So far, no medical treatment is available for cholesteatoma (C) and the only effective therapy is complete surgical removal, but recurrence is common even after surgical treatment. While C is classically divided into two clinical phenotypes, congenital and acquired, only a few studies have focused on its potential biomarkers. This study aims to revise the literature to identify which biomarkers can define the endotype of C. Methods: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) process to identify published experimental articles about molecular biomarkers in C. Results: KGF and its receptor, MMP-9, KRT-1, KRT-10, and MIF might be considered biomarkers of recurrence, whereas Ki-67, TLR-4, RANKL, IL17, MMP-2, MMP-9, IL6, TNF-α, should be considered more specifically as biomarkers of bony erosion. Conclusions: These results are interesting especially from a prognostic point of view, nevertheless more studies are needed to search new biomarkers of C that could completely change not only the therapeutic standards of the disease, but also the clinical history of C itself in the era of precision medicine. Full article

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

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15 pages, 3546 KiB

Open AccessArticle

Lymphatic Tissue Transfer: Ultrasound-Guided Description and Preoperative Planning of Vascularised Lymph Nodes, Lymphatic Units, and Lymphatic Vessels Transfers

by Giuseppe Visconti, Alessandro Bianchi, Marzia Salgarello, Alba Di Leone, Akitatsu Hayashi, Riccardo Masetti and Gianluca Franceschini

J. Pers. Med. 2022, 12(8), 1346; https://doi.org/10.3390/jpm12081346 - 21 Aug 2022

Cited by 6 | Viewed by 3459

Abstract

Background: The modern concept of lymphatic transfer includes vascularised lymph node transfer (VLNT), lymphatic vessels transfer (lymph interpositional flap transfer, LIFT) and lymphatic system transfer (vascularised lymph nodes and afferent lymphatics, LYST). The aim of this paper was to report our experience with [...] Read more.

Background: The modern concept of lymphatic transfer includes vascularised lymph node transfer (VLNT), lymphatic vessels transfer (lymph interpositional flap transfer, LIFT) and lymphatic system transfer (vascularised lymph nodes and afferent lymphatics, LYST). The aim of this paper was to report our experience with different types of lymphatic transfer. Patients and Method: From June 2016 to June 2020, 30 consecutive patients affected by extremity lymphedema and 15 patients affected by post-traumatic lower extremity soft tissue defects, underwent lymphatic transfer (VLNT, LYST or LIFT). All cases were preoperatively evaluated by both high frequency and ultra-high frequency ultrasound. Flap features were recorded, as well as qualitative and quantitative outcomes at 1 year postoperative. Results: The mean postoperative lymphedema index reduction was 7.2 ± 5.7 for upper extremity and 20.7 ± 7.1 for lower extremity. No dismission of compression garments occurred, 12 patients (26%) referred more stable results of physical treatment and 1 case showed a 1-class compression reduction. All the LIFTs aimed as preventive did not develop post-traumatic lymphedema. In all cases of distal placement of VLNT and/or LYST, patients were dissatisfied with the aesthetic appearance of reconstruction, while no donor site scar disappointment was referred. Conclusion: When LVA is not feasible, LTT may represent a valid treatment option. This report was aimed at comprehensively describing and assessing how different lymphatic tissue transfer modalities may fulfil the different reconstructive needs of lymphedema patients. Full article

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6 pages, 528 KiB

Open AccessArticle

Changing Trends in Surgical Management of Nephrolithiasis among Young Adults: A 15-Year Population-Based Study

by Dorit E. Zilberman, Tomer Erlich, Nir Kleinmann, Itay M. Sabler, Amos Neheman and Guy Verhovsky

J. Pers. Med. 2022, 12(8), 1345; https://doi.org/10.3390/jpm12081345 - 21 Aug 2022

Cited by 4 | Viewed by 1863

Abstract

Background: Increases in obesity and diabetes rates among all ages have led to a greater prevalence of nephrolithiasis worldwide. We aimed to explore the changing trends in surgical management of nephrolithiasis in young adults over a 15 year period. Methods: We reviewed medical [...] Read more.

Background: Increases in obesity and diabetes rates among all ages have led to a greater prevalence of nephrolithiasis worldwide. We aimed to explore the changing trends in surgical management of nephrolithiasis in young adults over a 15 year period. Methods: We reviewed medical records of military personnel for information on the diagnosis and care of nephrolithiasis before and during active service between 2007–2021, divided into three 5 year periods: 2007–2011, 2012–2016, and 2017–2021. Demographic, clinical, radiological, and surgical data were retrieved for the analysis of changing trends. Results: The records of 1,117,692 recruits yielded 7383 (0.66%) with stone-related surgeries, of whom 1885 were operated during military service. Their median age was 19.6 years (interquartile range [IQR] 16.8–21.2), 829 (70%) were males, and the cohort’s median body mass index was 23.6 (IQR 17.3–26.1). There was a dramatic decline in shock wave lithotripsy (SWL) prevalence (35.1%, 10.4%, and 4.4%, respectively) with a continually increasing prevalence of ureteroscopy (URS)/retrograde intrarenal surgery (RIRS) (62.7%, 88.5%, and 94.6%, p = 0.01). Percutaneous nephrolithotomy (PCNL) procedures have become nearly extinct over time (0.8% in 2017–2021). The number of median-sized stones treated by URS/RIRS increased (7.5 mm, 8.2 mm, and 9.7 mm, p = 0.044), but not those treated by SWL/PCNL. The median length of medical leave for URS/RIRS and PCNL decreased significantly (7 vs. 4 days, p = 0.05 and 10 vs. 6 days, p = 0.036, respectively), with no comparable change for SWL. There was a substantial decline in ancillary procedures in the URS/RIRS groups (9%, 6.8%, and 3.1%, p < 0.01), but not in the SWL/PCNL groups. Conclusions: Advancements in technology and surgical training are leading to the extinction of SWL and the adoption of URS/RIRS as the new standard of care for nephrolithiasis among young adults. Full article

(This article belongs to the Special Issue Advancements in Minimally Invasive Urological Surgery and Endourology)

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14 pages, 1864 KiB

Open AccessReview

Structured Reporting in Radiological Settings: Pitfalls and Perspectives

by Vincenza Granata, Federica De Muzio, Carmen Cutolo, Federica Dell’Aversana, Francesca Grassi, Roberta Grassi, Igino Simonetti, Federico Bruno, Pierpaolo Palumbo, Giuditta Chiti, Ginevra Danti and Roberta Fusco

J. Pers. Med. 2022, 12(8), 1344; https://doi.org/10.3390/jpm12081344 - 21 Aug 2022

Cited by 10 | Viewed by 2531

Abstract

Objective: The aim of this manuscript is to give an overview of structured reporting in radiological settings. Materials and Method: This article is a narrative review on structured reporting in radiological settings. Particularly, limitations and future perspectives are analyzed. RESULTS: The radiological report [...] Read more.

Objective: The aim of this manuscript is to give an overview of structured reporting in radiological settings. Materials and Method: This article is a narrative review on structured reporting in radiological settings. Particularly, limitations and future perspectives are analyzed. RESULTS: The radiological report is a communication tool for the referring physician and the patients. It was conceived as a free text report (FTR) to allow radiologists to have their own individuality in the description of the radiological findings. However, this form could suffer from content, style, and presentation discrepancies, with a probability of transferring incorrect radiological data. Quality, datafication/quantification, and accessibility represent the three main goals in moving from FTRs to structured reports (SRs). In fact, the quality is related to standardization, which aims to improve communication and clarification. Moreover, a “structured” checklist, which allows all the fundamental items for a particular radiological study to be reported and permits the connection of the radiological data with clinical features, allowing a personalized medicine. With regard to accessibility, since radiological reports can be considered a source of research data, SR allows data mining to obtain new biomarkers and to help the development of new application domains, especially in the field of radiomics. Conclusions: Structured reporting could eliminate radiologist individuality, allowing a standardized approach. Full article

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

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12 pages, 966 KiB

Open AccessArticle

The Anesthetic Strategy for Patients with Mucopolysaccharidoses: A Retrospective Cohort Study

by Hsuan-Chih Lao, Ying-Chun Lin, Muh-Lii Liang, Ying-Wei Yang, Ya-Hsien Huang, Ying-Lun Chan, Yung-Wei Hsu, Shuan-Pei Lin, Chih-Kuang Chuang, Jen-Kun Cheng and Hsiang-Yu Lin

J. Pers. Med. 2022, 12(8), 1343; https://doi.org/10.3390/jpm12081343 - 21 Aug 2022

Cited by 4 | Viewed by 2459

Abstract

Anesthesia for patients with mucopolysaccharidoses (MPS) is quite challenging due to vital systemic dysfunction following progressive accumulation of lysosomal glycosaminoglycans. Previous studies focused on perioperative difficult airway management under general anesthesia but rarely depicted the concern of choosing the size of the endotracheal [...] Read more.

Anesthesia for patients with mucopolysaccharidoses (MPS) is quite challenging due to vital systemic dysfunction following progressive accumulation of lysosomal glycosaminoglycans. Previous studies focused on perioperative difficult airway management under general anesthesia but rarely depicted the concern of choosing the size of the endotracheal tube (ETT) as well as neuraxial anesthesia. This study aimed to analyze the overall anesthetic management and related complications for a thorough anesthetic strategy. Within the study period from 2002 to 2021, each record of the anesthetic and perioperative quality assurance/improvement system for patients with a diagnosis of MPS at MacKay Memorial Hospital was retrospectively reviewed. A total of 51 individuals with 151 anesthesia for 163 interventions were cohort studied, and there were 136 general anesthesia and 15 neuraxial anesthesia. We found that the most common interventions for MPS patients were otolaryngological surgeries (49.6%). Additionally, a secured airway played a marked preference for the most general anesthesia (87.1%). The incidence of difficult intubation was 12.5%. In view of ETT size, a smaller than estimated size was used in MPS type II, III, IV, and VI patients and also in patients who received intubation with multiple attempts. However, a larger than estimated size of ETT was adopted whilst choosing cuffed ones. For neuraxial anesthesia, two failed spinal anesthesia procedures were converted to general anesthesia and 73 percent of the patients received perioperative sedation. In conclusion, through the individualized anesthetic strategy and build-up of an experienced team for airway management, high-quality anesthesia can be ensured in each patient. Full article

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

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9 pages, 514 KiB

Open AccessReview

A Review of Functional Outcomes after the App-Based Rehabilitation of Patients with TKA and THA

by Henrik Constantin Bäcker, Chia H. Wu, Dominik Pförringer, Wolf Petersen, Ulrich Stöckle and Karl F. Braun

J. Pers. Med. 2022, 12(8), 1342; https://doi.org/10.3390/jpm12081342 - 21 Aug 2022

Cited by 10 | Viewed by 2521

Abstract

Following the outbreak of SARS-CoV-2, several elective surgeries were cancelled, and rehabilitation units were closed. This has led to difficulties for patients seeking access to rehabilitation in order to achieve the best possible outcome. New applications with or without sensors were developed to [...] Read more.

Following the outbreak of SARS-CoV-2, several elective surgeries were cancelled, and rehabilitation units were closed. This has led to difficulties for patients seeking access to rehabilitation in order to achieve the best possible outcome. New applications with or without sensors were developed to address this need, but the outcome has not been examined in detail yet. The aim of this study was to perform a systematic literature review on smart phone applications for patients suffering from hip and knee osteoarthritis after arthroplasty. The MEDLINE/PubMed and Google databases were queried using the search term “[APP] AND [ORTHOPEDIC]” according to PRISMA guidelines. All prospective studies investigating rehabilitation applications reporting the functional outcome in hip and knee osteoarthritis after arthroplasty were included. The initial search yielded 420 entries, but only 9 publications met the inclusion criteria, accounting for 1067 patients. In total, 518 patients were in the intervention group, and 549 patients were in the control group. The average follow-up was 9.5 ± 8.1 months (range: 3 to 23.4 months). Overall, significantly lower A-VAS values were observed for the interventional group in the short term (p = 0.002). There were no other significant differences observed between the two groups. Smart phone applications provide an alternative to in-person sessions that may improve access for patients after total joint arthroplasty. Our study found there are significant improvements in the short term by using this approach. In combination with a blue-tooth-enabled sensor for isometric exercises, patients can even receive real-time feedback after total knee arthroplasty. Full article

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

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13 pages, 510 KiB

Open AccessReview

Intradermal Allergen Immunotherapy for Allergic Rhinitis: Current Evidence

by Kawita Atipas, Dichapong Kanjanawasee and Pongsakorn Tantilipikorn

J. Pers. Med. 2022, 12(8), 1341; https://doi.org/10.3390/jpm12081341 - 21 Aug 2022

Cited by 4 | Viewed by 2684

Abstract

Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated inflammatory disease that is induced by allergen introduction to the nasal mucosa, which triggers an inflammatory response. The current treatments for AR include allergen avoidance and pharmacotherapy; however, allergen-specific immunotherapy (AIT) is the only treatment [...] Read more.

Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated inflammatory disease that is induced by allergen introduction to the nasal mucosa, which triggers an inflammatory response. The current treatments for AR include allergen avoidance and pharmacotherapy; however, allergen-specific immunotherapy (AIT) is the only treatment that can be employed to modify immunologic responses and to achieve a cure for allergic diseases. The current standard routes of AIT administration are the subcutaneous and sublingual routes. Alternatively, the dermis contains a high density of dermal dendritic cells that act as antigen-presenting cells, so intradermal administration may confer added advantages and increase the efficacy of AIT. Moreover, intradermal immunotherapy (IDIT) may facilitate a reduction in the allergen dosage and a shortening of the treatment duration. The aim of this review was to search and evaluate the current evidence specific to IDIT, including its modified formulations, such as allergoids and peptides. The results of this review reveal conflicting evidence that suggests that the overall benefit of IDIT remains unclear. As such, further clinical trials are needed to establish the clinical utility of IDIT, and to determine the optimal treatment-related protocols. Full article

(This article belongs to the Special Issue The Present and Future of Allergen Immunotherapy in Personalized Medicine)

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21 pages, 342 KiB

Open AccessReview

Human-Induced Pluripotent Stem Cell Technology: Toward the Future of Personalized Psychiatry

by Alessandra Alciati, Angelo Reggiani, Daniela Caldirola and Giampaolo Perna

J. Pers. Med. 2022, 12(8), 1340; https://doi.org/10.3390/jpm12081340 - 20 Aug 2022

Cited by 10 | Viewed by 4336

Abstract

The polygenic and multifactorial nature of many psychiatric disorders has hampered implementation of the personalized medicine approach in clinical practice. However, induced pluripotent stem cell (iPSC) technology has emerged as an innovative tool for patient-specific disease modeling to expand the pathophysiology knowledge and [...] Read more.

The polygenic and multifactorial nature of many psychiatric disorders has hampered implementation of the personalized medicine approach in clinical practice. However, induced pluripotent stem cell (iPSC) technology has emerged as an innovative tool for patient-specific disease modeling to expand the pathophysiology knowledge and treatment perspectives in the last decade. Current technologies enable adult human somatic cell reprogramming into iPSCs to generate neural cells and direct neural cell conversion to model organisms that exhibit phenotypes close to human diseases, thereby effectively representing relevant aspects of neuropsychiatric disorders. In this regard, iPSCs reflect patient pathophysiology and pharmacological responsiveness, particularly when cultured under conditions that emulate spatial tissue organization in brain organoids. Recently, the application of iPSCs has been frequently associated with gene editing that targets the disease-causing gene to deepen the illness pathophysiology and to conduct drug screening. Moreover, gene editing has provided a unique opportunity to repair the putative causative genetic lesions in patient-derived cells. Here, we review the use of iPSC technology to model and potentially treat neuropsychiatric disorders by illustrating the key studies on a series of mental disorders, including schizophrenia, major depressive disorder, bipolar disorder, and autism spectrum disorder. Future perspectives will involve the development of organ-on-a-chip platforms that control the microenvironmental conditions so as to reflect individual pathophysiological by adjusting physiochemical parameters according to personal health data. This strategy could open new ways by which to build a disease model that considers individual variability and tailors personalized treatments. Full article

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

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5 pages, 185 KiB

Open AccessCommentary

Direct Oral Anticoagulants in Old and Frail Patients with Atrial Fibrillation: The Advantages of an Anticoagulation Service

by Maria Cristina Vedovati and Giancarlo Agnelli

J. Pers. Med. 2022, 12(8), 1339; https://doi.org/10.3390/jpm12081339 - 20 Aug 2022

Viewed by 1504

Abstract

Despite the recent advancements, oral anticoagulation is still challenging in some patients and this is the case for old and frail patients. The large majority of frail patients with atrial fibrillation should receive anticoagulation since the associated benefits outweigh the risk of bleeding. [...] Read more.

Despite the recent advancements, oral anticoagulation is still challenging in some patients and this is the case for old and frail patients. The large majority of frail patients with atrial fibrillation should receive anticoagulation since the associated benefits outweigh the risk of bleeding. A multidisciplinary consensus document on the use and prescription of direct oral anticoagulants (DOACs) in older and frail patients with atrial fibrillation has been recently published. In this manuscript we provide a comment on this document and add insights into the management of these patients. The new DOAC age had imposed a paradigm shift in the management of patients with the need for clinically-oriented services rather than laboratory-oriented services. In this paper we provide tools for a structured patient-oriented DOACs treatment service supported by a multidisciplinary approach. Full article

(This article belongs to the Special Issue Diagnosis, Treatment and Prognosis of Cardiovascular Disease)

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Open AccessArticle

Efficacy of Intravenous Elosulfase Alfa for Mucopolysaccharidosis Type IVA: A Systematic Review and Meta-Analysis

by Chung-Lin Lee, Chih-Kuang Chuang, Yu-Min Syu, Huei-Ching Chiu, Yuan-Rong Tu, Yun-Ting Lo, Ya-Hui Chang, Hsiang-Yu Lin and Shuan-Pei Lin

J. Pers. Med. 2022, 12(8), 1338; https://doi.org/10.3390/jpm12081338 - 20 Aug 2022

Cited by 2 | Viewed by 2345

Abstract

Mucopolysaccharidosis type IVA (MPS IVA or Morquio A), a lysosomal storage disease with an autosomal recessive inherited pattern, is induced by GALNS gene mutations causing deficiency in N-acetylgalactosamine-6-sulfatase activity (GALNS; EC 3.1.6.4). Currently, intravenous (IV) enzyme replacement therapy (ERT) with elosulfase alfa is [...] Read more.

Mucopolysaccharidosis type IVA (MPS IVA or Morquio A), a lysosomal storage disease with an autosomal recessive inherited pattern, is induced by GALNS gene mutations causing deficiency in N-acetylgalactosamine-6-sulfatase activity (GALNS; EC 3.1.6.4). Currently, intravenous (IV) enzyme replacement therapy (ERT) with elosulfase alfa is employed for treating MPS IVA patients. A systematic literature review was conducted to evaluate the efficacy and safety of IV elosulfase alfa for MPS IVA by searching the National Center for Biotechnology Information, U.S. National Library of Medicine National Institutes of Health (PubMed), Excerpta Medica dataBASE, and Cochrane Library databases, limited to clinical trials. Four cohort studies and two randomized controlled trials, with a total of 550 participants (327 on ERT treatment versus 223 on placebo treatment), satisfied the inclusion criteria. Pooled analysis of proportions and confidence intervals were also utilized to systematically review clinical cohort studies and trials. Per the pooled proportions analysis, the difference in means of urinary keratan sulfate (uKS), 6-min walk test, 3-min stair climb test, self-care MPS-Health Assessment Questionnaire, caregiver assistance and mobility, forced vital capacity, the first second of forced expiration, and maximal voluntary ventilation between the ERT and placebo treatment groups were −0.260, −0.102, −0.182, −0.360, −0.408, −0.587, −0.293, −0.311, and −0.213, respectively. Based on the currently available data, our meta-analysis showed that there is uKS, physical performance, quality of life, and respiratory function improvements with ERT in MPS IVA patients. It is optimal to start ERT after diagnosis. Full article

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

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13 pages, 453 KiB

Open AccessArticle

History of Endometriosis Is Independently Associated with an Increased Risk of Ovarian Cancer

by Antonio Sarría-Santamera, Zaukiya Khamitova, Arnur Gusmanov, Milan Terzic, Mar Polo-Santos, Miguel A. Ortega and Angel Asúnsolo

J. Pers. Med. 2022, 12(8), 1337; https://doi.org/10.3390/jpm12081337 - 20 Aug 2022

Cited by 4 | Viewed by 2306

Abstract

Background: Endometriosis is a complex gynecologic disorder that has been associated with a higher risk of ovarian cancer. The purpose of this work is to determine to what extent a history of endometriosis is a risk factor for ovarian cancer in a Spanish [...] Read more.

Background: Endometriosis is a complex gynecologic disorder that has been associated with a higher risk of ovarian cancer. The purpose of this work is to determine to what extent a history of endometriosis is a risk factor for ovarian cancer in a Spanish population. Methods: A retrospective case–control study was conducted using de-identified data from the Spanish National Health System’s “Primary Care Clinical Database” and “Hospital Minimum Basic Data Set” for the period 2013–2017. Multiple logistics regression analysis was conducted to determine associations between ovarian cancer and endometriosis controlled by sociodemographic characteristics and comorbidities. Results: Data from 608,980 women were analyzed, with 4505 presenting ovarian cancer. Endometriosis patients were shown to have a 2.66-fold increased risk of ovarian cancer when compared to those who did not have endometriosis by controlling age and other relevant comorbidities. Conclusions: This case–control study based on clinical administrative data has found that a history of endometriosis is independently associated with an increased risk of ovarian cancer. More research is needed to determine if a history of endometriosis affects survival results in ovarian cancer patients. Full article

(This article belongs to the Special Issue Diagnostics and Interventional Procedures in Gynecological Tumors)

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12 pages, 827 KiB

Open AccessArticle

Radiosurgery and Stereotactic Brain Radiotherapy with Systemic Therapy in Recurrent High-Grade Gliomas: Is It Feasible? Therapeutic Strategies in Recurrent High-Grade Gliomas

by Fabiana Gregucci, Alessia Surgo, Roberta Carbonara, Letizia Laera, Maria Paola Ciliberti, Maria Annunziata Gentile, Morena Caliandro, Nicola Sasso, Ilaria Bonaparte, Vincenzo Fanelli, Romina Tortora, Eleonora Paulicelli, Giammarco Surico, Giuseppe Lombardi, Francesco Signorelli and Alba Fiorentino

J. Pers. Med. 2022, 12(8), 1336; https://doi.org/10.3390/jpm12081336 - 20 Aug 2022

Cited by 7 | Viewed by 2958

Abstract

Purpose. For recurrent high-grade gliomas (HGG), no standard therapeutic approach has been reported; thus, surgery, chemotherapy, and re-irradiation (re-RT) may all be proposed. The aim of the study was to evaluate safety and efficacy of re-RT by radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) [...] Read more.

Purpose. For recurrent high-grade gliomas (HGG), no standard therapeutic approach has been reported; thus, surgery, chemotherapy, and re-irradiation (re-RT) may all be proposed. The aim of the study was to evaluate safety and efficacy of re-RT by radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) in association to chemotherapy in patients with recurrent HGG. Material/Methods: All patients with histological diagnosis of HGG that suffered by recurrent disease diagnosed by magnetic resonance imaging (MRI), according to Response Assessment in Neuro-Oncology (RANO) criteria, after primary/adjuvant chemo-radiotherapy treatment and underwent to re-RT by SRS/FSRT were included in the analysis. Second-line chemotherapy was administered. Outcomes were evaluated by neurological examination and brain MRI performed 1 month after re-RT and then every 2–3 months. Results: From November 2019 to September 2021, 30 patients presenting recurrent HGG underwent re-RT. Median dose was 24 Gy (range 15–36 Gy), and median fractions was 5 (range 1–6). Twenty-one patients (70%) had RPA class ≤ IV. One patient had a histological diagnosis of anaplastic oligodendroglioma, 24 patients (80%) were affected by glioblastoma (GBM) including 3 cases of multifocal form, and 5 patients (17%) by anaplastic astrocytoma. Median time between primary/adjuvant RT and disease recurrence was 8 months. In six cases (20%) re-operation was performed, and in most cases (87%), a second line of systemic therapy was administrated. At a median follow-up time from recurrence of 13 months (range 6–56 months), 10 patients (33%) were alive: 2 patients with partial response disease, 7 patients with stable disease, and 1 patient with out-field progression disease. Of the 20 patients who died (67%), 15 (75%) died for progression disease and 5 (25%) for other causes (3 due to septic event, 1 due to thrombo-embolic event, and 1 due to car accident). Median OS and PFS after recurrence were 12.1 and 11.2 months. Six-month and one-year OS were, respectively, 81% and 51%. No acute or late neurological side effects grade ≥ 2 and no case of radio-necrosis were reported. One patient experienced, after reintervention and during Regorafenib treatment (administered 40 days after surgery), dehiscence of the surgical wound. In three cases, grade 2 distal paresthesia was reported. Grade 3–4 hematologic toxicity occurred in seven cases. Three case of grade 5 toxicities during chemotherapy were reported: three septic events and one thrombo-embolic event. Conclusion. Re-RT with SRT/FSRT in association with second-line systemic therapy is a safe and feasible treatment for patients with HGG recurrence. Validation of these results by prospective studies is needed. Full article

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

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16 pages, 2093 KiB

Open AccessReview

Testicular Immunity and Its Connection with the Microbiota. Physiological and Clinical Implications in the Light of Personalized Medicine

by Luigi Santacroce, Ciro Imbimbo, Andrea Ballini, Felice Crocetto, Salvatore Scacco, Stefania Cantore, Erika Di Zazzo, Marica Colella and Emilio Jirillo

J. Pers. Med. 2022, 12(8), 1335; https://doi.org/10.3390/jpm12081335 - 20 Aug 2022

Cited by 12 | Viewed by 3573

Abstract

Reproduction is a complex process, which is based on the cooperation between the endocrine–immune system and the microbiota. Testicular immunity is characterized by the so-called immune privilege, a mechanism that avoids autoimmune attacks against proteins expressed by spermatozoa. Testicular microbiota is connected with [...] Read more.

Reproduction is a complex process, which is based on the cooperation between the endocrine–immune system and the microbiota. Testicular immunity is characterized by the so-called immune privilege, a mechanism that avoids autoimmune attacks against proteins expressed by spermatozoa. Testicular microbiota is connected with the gut microbiota, the most prevalent site of commensals inthe body. Both microbiotas take part inthe development of the immune system and protection againstpathogen invasion. Dysbiosis is caused by concurrent pathologies, such as obesity, diabetes, infections and trauma. The substitution of beneficial bacteria with pathogens may lead to destruction of spermatozoa directly or indirectly and, ultimately, to male infertility. Novel therapeutic interventions, i.e., nutritional interventions and supplementation of natural products, such as, probiotics, prebiotics, antioxidants and polyphenols, may lead to the restoration of the otherwise-impaired male reproductive potential, even if experimental and clinical results are not always concordant. In this review, the structure and immune function of the testis will be described with special reference to the blood–testisbarrier. The regulatory role of both the gut and testicular microbiota will be illustrated in health and disease, also emphasizing therapeutic attempts with natural products for the correction of male infertility, in the era of personalized medicine. Full article

(This article belongs to the Section Omics/Informatics)

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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 4747

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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13 pages, 2479 KiB

Open AccessArticle

The Adjuvant Therapy of Intravenous Laser Irradiation of Blood (ILIB) on Pain and Sleep Disturbance of Musculoskeletal Disorders

by (Jimmy) Chun-Ming Fu, Nai-Kuang Wang, Yuan-Yang Cheng and Shin-Tsu Chang

J. Pers. Med. 2022, 12(8), 1333; https://doi.org/10.3390/jpm12081333 - 19 Aug 2022

Cited by 6 | Viewed by 4495

Abstract

(1) Background: Musculoskeletal pain is both intractable and irritating. Intravenous Laser Irradiation of Blood (ILIB) therapy has been used as pain control treatment for this condition. However, there remains a lack of clear evidence regarding ILIB on pain control. This study aimed to [...] Read more.

(1) Background: Musculoskeletal pain is both intractable and irritating. Intravenous Laser Irradiation of Blood (ILIB) therapy has been used as pain control treatment for this condition. However, there remains a lack of clear evidence regarding ILIB on pain control. This study aimed to reveal the result of changes in patient pain intensity after receiving ILIB therapy. (2) Methods: We conducted a retrospective analysis of pain scores and sleep quality from 76 patients diagnosed with musculoskeletal disease who received three courses of ILIB therapy. Each course included ten sessions of ILIB treatment over ten consecutive days. During ILIB therapy, patients were inserted with a laser fiber optic needle which irradiated blood cells via a 632.8 nm Helium-Neon laser light over a period of 60 min. Pain scores were evaluated using the Visual Analogue Scale (VAS), whereas sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). These scores would be recorded both before and after each ILIB treatment course. (3) Results: The mean of all patients’ initial VAS score was 5.35. After completing three courses of ILIB treatment, the mean VAS score decreased to 2.2, which indicated a significant reduction in pain intensity. Additionally, patients experienced sleep quality improvement levels from PSQI 8.97 to 5.53 upon completion of three courses of ILIB treatment. (4) Conclusions: Intravenous Laser Irradiation of Blood (ILIB) resulted in a positive pain control effect on patients with musculoskeletal disease, especially for those with moderate to severe pain intensity (initial VAS score >4). Additionally, patients experienced better sleep quality as a result of their pain relief after receiving ILIB treatment. Full article

(This article belongs to the Section Mechanisms of Diseases)

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Open AccessArticle

Echocardiographic and Cardiac MRI Comparison of Longitudinal Strain and Strain Rate in Cancer Patients Treated with Immune Checkpoint Inhibitors

by Jibran Mirza, Sunitha Shyam Sunder, Badri Karthikeyan, Sharma Kattel, Saraswati Pokharel, Brian Quigley and Umesh C. Sharma

J. Pers. Med. 2022, 12(8), 1332; https://doi.org/10.3390/jpm12081332 - 19 Aug 2022

Cited by 3 | Viewed by 2186

Abstract

Background: Immune checkpoint inhibitor (ICI)-induced cardiac side effects in cancer patients are increasingly being recognized and can be fatal. There is no standardized cardiac imaging test to examine the effects of ICIs in myocardial morphology and function. Objective: To study the utility of [...] Read more.

Background: Immune checkpoint inhibitor (ICI)-induced cardiac side effects in cancer patients are increasingly being recognized and can be fatal. There is no standardized cardiac imaging test to examine the effects of ICIs in myocardial morphology and function. Objective: To study the utility of echocardiography and cardiac MRI in examining regional and global changes arising from ICI-induced myocarditis and cardiomyopathy in high-risk subjects suspected to have developed ICI cardiomyopathy. Methods: We studied eight consecutive patients referred for cardiac MRI (CMR) from a comprehensive cancer center for suspected ICI-induced myocarditis and compared the data with sixteen age-matched controls. Using newly developed strain analysis algorithms, we measured myocardial strain and strain rates using echocardiography and CMR. Then, we compared the mean longitudinal strain and strain rates derived from echocardiography and CMR in the same ICI-treated cohort of patients (n = 8). They underwent both of these imaging studies with images taken 24–48 h apart and followed up prospectively within the same hospital course. Results: All our cases had preserved ejection fraction (EF) > 50%. Echocardiogram showed reduced mean systolic longitudinal strain (LS, %) (ICI: −12.381 ± 4.161; control: −19.761 ± 1.925; p < 0.001), peak systolic strain rate (SR_S, s⁻¹) (ICI: −0.597 ± 0.218; control: −0.947 ± 0.135; p = 0.002) and early diastolic strain rate (SR_E, s⁻¹) (ICI: 0.562 ± 0.295; control: 1.073 ± 0.228; p = 0.002) in ICI-treated cases. Direct comparison between the echocardiogram vs. CMR obtained within the same hospital course demonstrated strong a correlation of LS scores (r = 0.83, p = 0.012) and SR_S scores (r = 0.71, p = 0.048). The Bland–Altman plots showed that 95% of the data points fitted within the ±1.96 SD of the mean difference, suggesting an agreement among these two imaging modalities. Conclusion: In this feasibility cohort study, both echocardiography- and CMR-based strain indices illustrate changes in myocardial contractility and relaxation suggestive of ICI-induced cardiomyopathy. Our data, after validation in a larger cohort, can form the basis of myocardial imaging in cancer patients treated with ICIs. Full article

(This article belongs to the Special Issue Personalized Medicine in Cardio-Oncology)

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2 pages, 162 KiB

Open AccessEditorial

Editorial on the Paper “The Epidemiology and Genetics of Hyperuricemia and Gout across Major Racial Groups: A Literature Review and Population Genetics Secondary Database Analysis” by Butler, Alghoubayshi and Roman

by Farah R. Zahir

J. Pers. Med. 2022, 12(8), 1331; https://doi.org/10.3390/jpm12081331 - 19 Aug 2022

Cited by 1 | Viewed by 1299

Abstract

This report by Butler et al [...] Full article

(This article belongs to the Section Epidemiology)

18 pages, 947 KiB

Open AccessArticle

Selecting Genetic Variants and Interactions Associated with Amyotrophic Lateral Sclerosis: A Group LASSO Approach

by Sofia Galvão Feronato, Maria Luiza Matos Silva, Rafael Izbicki, Ticiana D. J. Farias, Patrícia Shigunov, Bruno Dallagiovanna, Fabio Passetti and Hellen Geremias dos Santos

J. Pers. Med. 2022, 12(8), 1330; https://doi.org/10.3390/jpm12081330 - 19 Aug 2022

Cited by 3 | Viewed by 2286

Abstract

Amyotrophic lateral sclerosis (ALS) is a multi-system neurodegenerative disease that affects both upper and lower motor neurons, resulting from a combination of genetic, environmental, and lifestyle factors. Usually, the association between single-nucleotide polymorphisms (SNPs) and this disease is tested individually, which leads to [...] Read more.

Amyotrophic lateral sclerosis (ALS) is a multi-system neurodegenerative disease that affects both upper and lower motor neurons, resulting from a combination of genetic, environmental, and lifestyle factors. Usually, the association between single-nucleotide polymorphisms (SNPs) and this disease is tested individually, which leads to the testing of multiple hypotheses. In addition, this classical approach does not support the detection of interaction-dependent SNPs. We applied a two-step procedure to select SNPs and pairwise interactions associated with ALS. SNP data from 276 ALS patients and 268 controls were analyzed by a two-step group LASSO in 2000 iterations. In the first step, we fitted a group LASSO model to a bootstrap sample and a random subset of predictors (

25 %

) from the original data set aiming to screen for important SNPs and, in the second step, we fitted a hierarchical group LASSO model to evaluate pairwise interactions. An in silico analysis was performed on a set of variables, which were prioritized according to their bootstrap selection frequency. We identified seven SNPs (rs16984239, rs10459680, rs1436918, rs1037666, rs4552942, rs10773543, and rs2241493) and two pairwise interactions (rs16984239:rs2118657 and rs16984239:rs3172469) potentially involved in nervous system conservation and function. These results may contribute to the understanding of ALS pathogenesis, its diagnosis, and therapeutic strategy improvement. Full article

(This article belongs to the Special Issue Application of Bioinformatics in Precision Medicine)

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22 pages, 3051 KiB

Open AccessReview

MicroRNAs as Regulators of Cancer Cell Energy Metabolism

by Natarajaseenivasan Suriya Muthukumaran, Prema Velusamy, Charles Solomon Akino Mercy, Dianne Langford, Kalimuthusamy Natarajaseenivasan and Santhanam Shanmughapriya

J. Pers. Med. 2022, 12(8), 1329; https://doi.org/10.3390/jpm12081329 - 18 Aug 2022

Cited by 8 | Viewed by 3178

Abstract

To adapt to the tumor environment or to escape chemotherapy, cancer cells rapidly reprogram their metabolism. The hallmark biochemical phenotype of cancer cells is the shift in metabolic reprogramming towards aerobic glycolysis. It was thought that this metabolic shift to glycolysis alone was [...] Read more.

To adapt to the tumor environment or to escape chemotherapy, cancer cells rapidly reprogram their metabolism. The hallmark biochemical phenotype of cancer cells is the shift in metabolic reprogramming towards aerobic glycolysis. It was thought that this metabolic shift to glycolysis alone was sufficient for cancer cells to meet their heightened energy and metabolic demands for proliferation and survival. Recent studies, however, show that cancer cells rely on glutamine, lipid, and mitochondrial metabolism for energy. Oncogenes and scavenging pathways control many of these metabolic changes, and several metabolic and tumorigenic pathways are post-transcriptionally regulated by microRNA (miRNAs). Genes that are directly or indirectly responsible for energy production in cells are either negatively or positively regulated by miRNAs. Therefore, some miRNAs play an oncogenic role by regulating the metabolic shift that occurs in cancer cells. Additionally, miRNAs can regulate mitochondrial calcium stores and energy metabolism, thus promoting cancer cell survival, cell growth, and metastasis. In the electron transport chain (ETC), miRNAs enhance the activity of apoptosis-inducing factor (AIF) and cytochrome c, and these apoptosome proteins are directed towards the ETC rather than to the apoptotic pathway. This review will highlight how miRNAs regulate the enzymes, signaling pathways, and transcription factors of cancer cell metabolism and mitochondrial calcium import/export pathways. The review will also focus on the metabolic reprogramming of cancer cells to promote survival, proliferation, growth, and metastasis with an emphasis on the therapeutic potential of miRNAs for cancer treatment. Full article

(This article belongs to the Special Issue MiRNA Targets in Cancer: Diagnosis, Prognosis and Treatment)

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13 pages, 4782 KiB

Open AccessArticle

Enhanced Child Care: Contrast Correction for Pediatric Hip Ultrasound Using Hyperanalytic Wavelets

by Beatrice Arvinti, Emil Radu Iacob, Alexandru Isar, Daniela Iacob and Marius Costache

J. Pers. Med. 2022, 12(8), 1328; https://doi.org/10.3390/jpm12081328 - 18 Aug 2022

Viewed by 1565

Abstract

(1) Background: The prevention of critical situations is a key ability in medicine. Hip ultrasound for neonates is a standard procedure to prevent later critical outcomes, such as hip dysplasia. Additionally, the SARS-CoV-2 pandemic has put worldwide stress upon healthcare units, resulting often [...] Read more.

(1) Background: The prevention of critical situations is a key ability in medicine. Hip ultrasound for neonates is a standard procedure to prevent later critical outcomes, such as hip dysplasia. Additionally, the SARS-CoV-2 pandemic has put worldwide stress upon healthcare units, resulting often in a lack of sufficient medical personnel. This work aims to develop solutions to ease and speed up the process of coming to a correct diagnosis. (2) Methods: Traditional medical procedures are envisaged, but they are enhanced to reduce diagnosing errors due to the movements of the neonates. Echographic noise filtering and contrast correction methods are implemented the Hyperanalytic Wavelet Transform, combined with an adaptive Soft Thresholding Filter. The algorithm is tailored to infants’ structure and is tested on real ultrasounds provided by the “Victor Babes” University of Medicine and Pharmacy. Denoising and contrast correction problems are targeted. (3) Results: In available clinical cases, the noise affecting the image was reduced and the contrast was enhanced. (4) Discussion: We noticed that a significant amount of noise can be added to the image, as the patients are neonates and can hardly avoid movements. (5) Conclusions: The algorithm is personalized with no fixed reference value. Any device easing the clinical procedures of physicians has a practical medical application. Full article

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14 pages, 780 KiB

Open AccessArticle

What’s in a Name? Parents’ and Healthcare Professionals’ Preferred Terminology for Pathogenic Variants in Childhood Cancer Predisposition Genes

by Jacqueline D. Hunter, Eden G. Robertson, Kate Hetherington, David S. Ziegler, Glenn M. Marshall, Judy Kirk, Jonathan M. Marron, Avram E. Denburg, Kristine Barlow-Stewart, Meera Warby, Katherine M. Tucker, Brittany M. Lee, Tracey A. O’Brien and Claire E. Wakefield

J. Pers. Med. 2022, 12(8), 1327; https://doi.org/10.3390/jpm12081327 - 18 Aug 2022

Cited by 2 | Viewed by 3679

Abstract

Current literature/guidelines regarding the most appropriate term to communicate a cancer-related disease-causing germline variant in childhood cancer lack consensus. Guidelines also rarely address preferences of patients/families. We aimed to assess preferences of parents of children with cancer, genetics professionals, and pediatric oncologists towards [...] Read more.

Current literature/guidelines regarding the most appropriate term to communicate a cancer-related disease-causing germline variant in childhood cancer lack consensus. Guidelines also rarely address preferences of patients/families. We aimed to assess preferences of parents of children with cancer, genetics professionals, and pediatric oncologists towards terminology to describe a disease-causing germline variant in childhood cancer. Using semi-structured interviews we asked participants their most/least preferred terms from; ‘faulty gene,’ ‘altered gene,’ ‘gene change,’ and ‘genetic variant,’ analyzing responses with directed content analysis. Twenty-five parents, 6 genetics professionals, and 29 oncologists participated. An equal number of parents most preferred ‘gene change,’ ‘altered gene,’ or ‘genetic variant’ (n = 8/25). Parents least preferred ‘faulty gene’ (n = 18/25). Half the genetics professionals most preferred ‘faulty gene’ (n = 3/6); however this was least preferred by the remaining genetics professionals (n = 3/6). Many oncologists most preferred ‘genetic variant’ (n = 11/29) and least preferred ‘faulty gene’ (n = 19/29). Participants across all groups perceived ‘faulty gene’ as having negative connotations, potentially placing blame/guilt on parents/children. Health professionals described challenges selecting a term that was scientifically accurate, easily understood and not distressing to families. Lack of consensus highlights the need to be guided by families’ preferred terminology, while providing accurate explanations regarding implications of genetic findings. Full article

(This article belongs to the Special Issue Genetic Counseling and Genetic Testing in Precision Medicine)

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14 pages, 2103 KiB

Open AccessArticle

Long-Term Device Satisfaction and Safety after Cochlear Implantation in Children

by Milan Urík, Soňa Šikolová, Dagmar Hošnová, Vít Kruntorád, Michal Bartoš and Petr Jabandžiev

J. Pers. Med. 2022, 12(8), 1326; https://doi.org/10.3390/jpm12081326 - 18 Aug 2022

Viewed by 2121

Abstract

(1) Objectives: For full benefit in children implanted with a cochlear implant (CI), wearing the device all waking hours is necessary. This study focuses on the relationship between daily use and audiological outcomes, with the hypothesis that frequent daily device use coincides with [...] Read more.

(1) Objectives: For full benefit in children implanted with a cochlear implant (CI), wearing the device all waking hours is necessary. This study focuses on the relationship between daily use and audiological outcomes, with the hypothesis that frequent daily device use coincides with high device satisfaction resulting in better functional gain (FG). Confounding factors such as implantation age, device experience and type of device were considered. (2) Results: Thirty-eight CI children (65 ears) were investigated. In total, 76.92% of the children were using their device for >12 h per day (h/d), 18.46% for 9–12 h/d, the remaining for 6–9 h/d and one subject reported 3 h/d. The revision rate up to the 90-month follow-up (F/U) was 4.6%. The mean FG was 59.00 ± 7.67 dB. The Audio Processor Satisfaction Questionnaire (APSQ) separated for single unit (SU) versus behind the ear (BTE) devices showed significantly better results for the latter in terms of wearing comfort (WC) (p = 0.00062). A correlation between device use and FG was found with a device experience of <2 years (n = 29; r² = 0.398), whereas no correlation was seen with ≥2 years of device experience (n = 36; r² = 0.0038). (3) Conclusion: This study found significant relationships between daily device use and FG, wearing comfort and long-term safety (90 months). Full article

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

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20 pages, 5664 KiB

Open AccessArticle

Hybrid Bayesian Network-Based Modeling: COVID-19-Pneumonia Case

by Ilia Vladislavovich Derevitskii, Nikita Dmitrievich Mramorov, Simon Dmitrievich Usoltsev and Sergey V. Kovalchuk

J. Pers. Med. 2022, 12(8), 1325; https://doi.org/10.3390/jpm12081325 - 17 Aug 2022

Cited by 5 | Viewed by 2871

Abstract

The primary goal of this paper is to develop an approach for predicting important clinical indicators, which can be used to improve treatment. Using mathematical predictive modeling algorithms, we examined the course of COVID-19-based pneumonia (CP) with inpatient treatment. Algorithms used include dynamic [...] Read more.

The primary goal of this paper is to develop an approach for predicting important clinical indicators, which can be used to improve treatment. Using mathematical predictive modeling algorithms, we examined the course of COVID-19-based pneumonia (CP) with inpatient treatment. Algorithms used include dynamic and ordinary Bayesian networks (OBN and DBN), popular ML algorithms, the state-of-the-art auto ML approach and our new hybrid method based on DBN and auto ML approaches. Predictive targets include treatment outcomes, length of stay, dynamics of disease severity indicators, and facts of prescribed drugs for different time intervals of observation. Models are validated using expert knowledge, current clinical recommendations, preceding research and classic predictive metrics. The characteristics of the best models are as follows: MAE of 3.6 days of predicting LOS (DBN plus FEDOT auto ML framework), 0.87 accuracy of predicting treatment outcome (OBN); 0.98 F1 score for predicting facts of prescribed drug (DBN). Moreover, the advantage of the proposed approach is Bayesian network-based interpretability, which is very important in the medical field. After the validation of other CP datasets for other hospitals, the proposed models can be used as part of the decision support systems for improving COVID-19-based pneumonia treatment. Another important finding is the significant differences between COVID-19 and non-COVID-19 pneumonia. 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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20 pages, 2096 KiB

Open AccessReview

Nanotechnologies in Obstetrics and Cancer during Pregnancy: A Narrative Review

by Serena Bertozzi, Bruna Corradetti, Luca Seriau, José Andrés Diaz Ñañez, Carla Cedolini, Arrigo Fruscalzo, Daniela Cesselli, Angelo Cagnacci and Ambrogio P. Londero

J. Pers. Med. 2022, 12(8), 1324; https://doi.org/10.3390/jpm12081324 - 17 Aug 2022

Cited by 7 | Viewed by 3424

Abstract

Nanotechnology, the art of engineering structures on a molecular level, offers the opportunity to implement new strategies for the diagnosis and management of pregnancy-related disorders. This review aims to summarize the current state of nanotechnology in obstetrics and cancer in pregnancy, focusing on [...] Read more.

Nanotechnology, the art of engineering structures on a molecular level, offers the opportunity to implement new strategies for the diagnosis and management of pregnancy-related disorders. This review aims to summarize the current state of nanotechnology in obstetrics and cancer in pregnancy, focusing on existing and potential applications, and provides insights on safety and future directions. A systematic and comprehensive literature assessment was performed, querying the following databases: PubMed/Medline, Scopus, and Endbase. The databases were searched from their inception to 22 March 2022. Five independent reviewers screened the items and extracted those which were more pertinent within the scope of this review. Although nanotechnology has been on the bench for many years, most of the studies in obstetrics are preclinical. Ongoing research spans from the development of diagnostic tools, including optimized strategies to selectively confine contrast agents in the maternal bloodstream and approaches to improve diagnostics tests to be used in obstetrics, to the synthesis of innovative delivery nanosystems for therapeutic interventions. Using nanotechnology to achieve spatial and temporal control over the delivery of therapeutic agents (e.g., commonly used drugs, more recently defined formulations, or gene therapy-based approaches) offers significant advantages, including the possibility to target specific cells/tissues of interest (e.g., the maternal bloodstream, uterus wall, or fetal compartment). This characteristic of nanotechnology-driven therapy reduces side effects and the amount of therapeutic agent used. However, nanotoxicology appears to be a significant obstacle to adopting these technologies in clinical therapeutic praxis. Further research is needed in order to improve these techniques, as they have tremendous potential to improve the accuracy of the tests applied in clinical praxis. This review showed the increasing interest in nanotechnology applications in obstetrics disorders and pregnancy-related pathologies to improve the diagnostic algorithms, monitor pregnancy-related diseases, and implement new treatment strategies. Full article

(This article belongs to the Special Issue Pregnancy Complication and Precision Medicine)

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J. Pers. Med., Volume 12, Issue 8 (August 2022) – 162 articles

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