Journal of Personalized Medicine

5 pages, 223 KiB

Open AccessEditorial

Clinical Updates for Gastrointestinal Malignancies

by Carmelo Laface and Riccardo Memeo

J. Pers. Med. 2023, 13(9), 1424; https://doi.org/10.3390/jpm13091424 - 21 Sep 2023

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Gastrointestinal (GI) cancers include hepatobiliary tumors, pancreatic cancer (PC), neuroendocrine tumors of the gastrointestinal tract, small bowel carcinomas, gastric cancer (GC), anal canal cancer, primary gastric and intestinal lymphomas, gastrointestinal stromal tumors (GISTs) and the most frequent colorectal cancer (CRC) [...] Full article

(This article belongs to the Special Issue Clinical Updates for Gastrointestinal Malignancies)

12 pages, 764 KiB

Open AccessArticle

Serum Levels of S100B Protein and Myelin Basic Protein as a Potential Biomarkers of Recurrent Depressive Disorders

by Lyudmila A. Levchuk, Olga V. Roschina, Ekaterina V. Mikhalitskaya, Elena V. Epimakhova, German G. Simutkin, Nikolay A. Bokhan and Svetlana A. Ivanova

J. Pers. Med. 2023, 13(9), 1423; https://doi.org/10.3390/jpm13091423 - 21 Sep 2023

Viewed by 922

Abstract

Nowadays, nervous tissue damage proteins in serum are considered promising drug targets and biomarkers of Mood Disorders. In a cross-sectional naturalistic study, the S100B, MBP and GFAP levels in the blood serum were compared between two diagnostic groups (patients with Depressive Episode (DE, [...] Read more.

Nowadays, nervous tissue damage proteins in serum are considered promising drug targets and biomarkers of Mood Disorders. In a cross-sectional naturalistic study, the S100B, MBP and GFAP levels in the blood serum were compared between two diagnostic groups (patients with Depressive Episode (DE, n = 28) and patients with Recurrent Depressive Disorder (RDD, n = 21)), and healthy controls (n = 25). The diagnostic value of serum markers was assessed by ROC analysis. In the DE group, we did not find changed levels of S100B, MBP and GFAP compared with controls. In the RDD group, we found decreased S100B level (p = 0.011) and increased MBP level (p = 0.015) in comparison to those in healthy controls. Provided ROC analysis indicates that MBP contributes to the development of a DE (AUC = 0.676; 95%Cl 0.525–0.826; p = 0.028), and S100B and MBP have a significant effect on the development of RDD (AUC = 0.732; 95%Cl 0.560–0.903; p = 0.013 and AUC = 0.712; 95%Cl 0.557–0.867; p = 0.015, correspondingly). The study of serum markers of nervous tissue damage in patients with a current DE indicates signs of disintegration of structural and functional relationships, dysfunction of gliotransmission, and impaired secretion of neurospecific proteins. Modified functions of astrocytes and oligodendrocytes are implicated in the pathophysiology of RDD. Full article

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15 pages, 785 KiB

Open AccessArticle

Risk Factors and Management Approaches for Staple Line Leaks Following Sleeve Gastrectomy: A Single-Center Retrospective Study of 402 Patients

by Georgios-Ioannis Verras, Francesk Mulita, Charalampos Lampropoulos, Dimitrios Kehagias, Oliver Curwen, Andreas Antzoulas, Ioannis Panagiotopoulos, Vasileios Leivaditis and Ioannis Kehagias

J. Pers. Med. 2023, 13(9), 1422; https://doi.org/10.3390/jpm13091422 - 21 Sep 2023

Cited by 2 | Viewed by 1045

Abstract

Sleeve gastrectomy (SG) has gained ever-increasing popularity among laparoscopic surgeons involved in bariatric surgery. This single-institution, retrospective cohort study aims to evaluate the prevalence of postoperative staple line leakage (PSLL) after LSG and identify risk factors for its development. We included patient data [...] Read more.

Sleeve gastrectomy (SG) has gained ever-increasing popularity among laparoscopic surgeons involved in bariatric surgery. This single-institution, retrospective cohort study aims to evaluate the prevalence of postoperative staple line leakage (PSLL) after LSG and identify risk factors for its development. We included patient data that underwent LSG at our institution for a span of 17 years—starting in January 2005 and ending in December 2022. We set the investigation of correlations of patient-related factors (age, weight, BMI, smoking status, presence of diabetes mellitus) with the occurrence of postoperative leaks. A total of 402 patients were included in our study. Of them, 26 (6.46%) developed PSLL. In total, 19 (73%) patients underwent percutaneous drainage and 14 patients (53.8%) were treated with intraluminal endoscopic stenting. Finally, five patients (19.2%) were treated with endoscopic clipping of the defect. Operative management was required in only one patient. There were no statistically significant differences in patient age, mean weight at the time of operation, and mean BMI. Abnormal drain amylase levels were associated with earlier detection of PSLL. More consideration needs to be given to producing a consensus regarding the management of PSLL, prioritizing nonoperative management with the combination of percutaneous drainage and endoscopic stenting as the safest and most efficient approach. Full article

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

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24 pages, 13694 KiB

Open AccessArticle

AI-Driven Decision Support for Early Detection of Cardiac Events: Unveiling Patterns and Predicting Myocardial Ischemia

by Luís B. Elvas, Miguel Nunes, Joao C. Ferreira, Miguel Sales Dias and Luís Brás Rosário

J. Pers. Med. 2023, 13(9), 1421; https://doi.org/10.3390/jpm13091421 - 21 Sep 2023

Cited by 1 | Viewed by 1388

Abstract

Cardiovascular diseases (CVDs) account for a significant portion of global mortality, emphasizing the need for effective strategies. This study focuses on myocardial infarction, pulmonary thromboembolism, and aortic stenosis, aiming to empower medical practitioners with tools for informed decision making and timely interventions. Drawing [...] Read more.

Cardiovascular diseases (CVDs) account for a significant portion of global mortality, emphasizing the need for effective strategies. This study focuses on myocardial infarction, pulmonary thromboembolism, and aortic stenosis, aiming to empower medical practitioners with tools for informed decision making and timely interventions. Drawing from data at Hospital Santa Maria, our approach combines exploratory data analysis (EDA) and predictive machine learning (ML) models, guided by the Cross-Industry Standard Process for Data Mining (CRISP-DM) methodology. EDA reveals intricate patterns and relationships specific to cardiovascular diseases. ML models achieve accuracies above 80%, providing a 13 min window to predict myocardial ischemia incidents and intervene proactively. This paper presents a Proof of Concept for real-time data and predictive capabilities in enhancing medical strategies. Full article

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

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12 pages, 1579 KiB

Open AccessArticle

Analysis of Degenerative and Isthmic Lumbar Spondylolisthesis from the Difference of Pelvic Parameters and the Degree of Degeneration through Imaging Data

by Zhide Liu, Guoyu Dai, Yong Cao and Chunyue Duan

J. Pers. Med. 2023, 13(9), 1420; https://doi.org/10.3390/jpm13091420 - 21 Sep 2023

Cited by 1 | Viewed by 1145

Abstract

Background: In previous studies, many imaging analyses have been conducted to explore the changes in the intervertebral disc degeneration (DD), facet joint osteoarthritis (FJOA), L4 inclination angle (L4IA), pelvis-related parameters, lumbar lordosis (LL), and paravertebral muscle (PVM) in the occurrence and development of [...] Read more.

Background: In previous studies, many imaging analyses have been conducted to explore the changes in the intervertebral disc degeneration (DD), facet joint osteoarthritis (FJOA), L4 inclination angle (L4IA), pelvis-related parameters, lumbar lordosis (LL), and paravertebral muscle (PVM) in the occurrence and development of degenerative spinal diseases via measuring the X-ray, CT, and MRI data of clinical patients. However, few studies have quantitatively investigated the pelvic parameters and the degree of spine degeneration in patients with degenerative lumbar spondylolisthesis (DLS) and isthmic lumbar spondylolisthesis (ILS). This study discusses the changes in the imaging parameters of DLS, ILS, and a control group; explores the correlation between different measurement parameters; and discusses their risk factors. Methods: We evaluated 164 patients with single L4-L5 grade 1 level degenerative lumbar spondylolisthesis (DLS group), 161 patients with single L4-L5 grade 1 level isthmic lumbar spondylolisthesis (ILS group), and 164 patients with non-specific back pain (control group). The grades of DD and FJOA as well as the percentage of the fat infiltration area (%FIA) of multifidus muscle (MM) at the L4-L5 level were measured via CT and MRI. Lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), the L4 inclination angle (L4IA), and sacral slope (SS) were measured via X-ray film, and the differences among the DLS group, ILS group, and control group were analyzed. Furthermore, the risk factors related to the incidences of the DLS and ILS groups were discussed. Results: First, the pelvis-related parameters of DLS and ILS patients were 51.91 ± 12.23 and 53.28 ± 11.12, respectively, while those of the control group were 40.13 ± 8.72 (p₁ < 0.001, p₂ < 0.001). Lumbar lordosis (LL) in DLS patients (39.34 ± 8.57) was significantly lower than in the control group (44.40 ± 11.79, p < 0.001). On the contrary, lumbar lordosis (LL) in the ILS group (55.16 ± 12.31) was significantly higher than in the control group (44.40 ± 11.79, p < 0.001). Secondly, the three groups of patients were characterized by significant variations in the L4 inclination angle (L4IA), disc degeneration (DD), facet joint osteoarthritis (FJOA), pelvis-related parameters, and paravertebral muscle (PVM) (p < 0.05). Finally, logistic regression suggests that the L4IA, FJOA, and PT may be risk factors for the occurrence of DLS, and the occurrence of ILS is correlated with the L4IA, FJOA, DD, PT, and LL. Conclusions: Compared with the control group, there are changes in pelvic parameters, the L4IA, LL, DD, FJOA, and PVM in DLS and ILS patients, and the degree is different. The parameters within the same group are related to each other, and DLS and ILS have different risk factors. The mechanical stability of the spine is affected by the parameter and angle changes, which may be of great significance for explaining the cause of spondylolisthesis, evaluating the health of the lumbar spine, and guiding the lifestyles of patients. Full article

(This article belongs to the Section Regenerative Medicine and Therapeutics)

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12 pages, 516 KiB

Open AccessArticle

Factors Affecting the Potential Efficacy of Intrauterine Platelet-Rich Plasma Infusion on Thin Endometrium in Women with Recurrent Implantation Failure

by Pin-Yao Lin, Chun-I Lee, Yi-Chun Chen, En-Hui Cheng, Chun-Chia Huang, Chung-I Chen, Tsung-Hsien Lee, Yu-Jen Lee and Maw-Sheng Lee

J. Pers. Med. 2023, 13(9), 1419; https://doi.org/10.3390/jpm13091419 - 21 Sep 2023

Cited by 2 | Viewed by 1068

Abstract

Optimizing endometrial thickness (EMT) is crucial for successful embryo implantation, but enhancing thin endometrium remains a significant challenge. Platelet-rich plasma (PRP)-derived therapies have emerged as a promising approach in reproductive medicine due to their capacity to facilitate tissue repair and regeneration. This study [...] Read more.

Optimizing endometrial thickness (EMT) is crucial for successful embryo implantation, but enhancing thin endometrium remains a significant challenge. Platelet-rich plasma (PRP)-derived therapies have emerged as a promising approach in reproductive medicine due to their capacity to facilitate tissue repair and regeneration. This study aims to identify the risk factors associated with the failure of intrauterine PRP infusion for thin endometrium in women with recurrent implantation failure (RIF). We retrospectively reviewed data from 77 women with RIF, all exhibiting an EMT of <7 mm. These women underwent programmed hormone therapy for frozen embryo transfer (FET) and received two autologous intrauterine PRP infusions. Following intrauterine PRP-lysate (PL) infusions, the mean increase in EMT was 1.9 ± 1.2 mm, with EMT reaching 7 mm in 86% of the cases (66/77; average EMT, 8.3 mm). We identified an exceedingly thin EMT as a risk factor impacting the therapeutic efficacy in increasing EMT (p = 0.04, OR: 3.16; 95% CI: 1.03–9.67). Additionally, the number of previous uterine surgeries emerged as a prognostic factor for pregnancy failure following PL infusion (p = 0.02, OR: 2.02; 95% CI: 1.12–3.64). Our findings suggest that an extremely thin EMT and a history of numerous uterine surgeries can impede successful pregnancy, even when an optimal EMT is achieved following PRP infusion. Full article

(This article belongs to the Special Issue Current Trends and Future Challenges in Assisted Reproduction)

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10 pages, 4158 KiB

Open AccessReview

Bladder Cancer during Pregnancy: A Review of the Literature

by Angelis Peteinaris, Paraskevas Perros, Ioannis Prokopakis, Zacharias Fasoulakis, Thomas Ntounis, Konstantinos Daglas, Ira Eirini Kostopoulou, Athina A. Samara, Konstantinos Pagonis, Vasileios Tatanis, Gabriel Faria-Costa, Rudi Xhaferi, Karen Arzumanyan, Begoña Ballesta Martínez, Athanasios Chionis, Vasilios Pergialiotis, George Daskalakis, Emmanuel N. Kontomanolis and Antonios Koutras

J. Pers. Med. 2023, 13(9), 1418; https://doi.org/10.3390/jpm13091418 - 21 Sep 2023

Viewed by 1155

Abstract

Bladder malignancy represents the fourth most common cancer in men and the eighth in women in the western world. Women under 75 years of age have a risk of 0.5–1% of developing bladder cancer. The diagnosis usually occurs between 65 and 70 years [...] Read more.

Bladder malignancy represents the fourth most common cancer in men and the eighth in women in the western world. Women under 75 years of age have a risk of 0.5–1% of developing bladder cancer. The diagnosis usually occurs between 65 and 70 years of age, whereas the mortality rate for women varies from 0.5 to 4 per 100,000 every year. Nulliparous women present a greater risk than women who have given birth. The risk is further decreased when parity increases. Theoretically, hormonal changes occurring during pregnancy play a protective role. Smoking and occupational exposure to specific chemicals are the most common risk factors of bladder cancer. Other risk factors such as chronic urinary tract inflammation, cyclophosphamide, radiotherapy, and familial correlation have been reported. The aim of this review is to highlight a rare combination, which is the co-existence of bladder malignancy and pregnancy. We present thirteen different cases of women who were diagnosed with malignant bladder tumors during their pregnancy. A review of the literature was conducted, focusing on the unspecific symptoms, possible diagnostic tools, and suitable treatment modalities. The management of bladder cancer in pregnancy is a challenging process. The fragile balance between the possible complications of pregnancy and maternal health is yet to be discussed. Full article

(This article belongs to the Special Issue Advances in Treatment of Urinary Bladder Cancer)

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13 pages, 2270 KiB

Open AccessArticle

Novel Interdisciplinary Enhanced Recovery after Surgery Protocol Implementation in Paediatric Orthopaedics

by Sławomir Zacha, Aleksander Szwed, Jakub Miegoń, Karolina Skonieczna-Żydecka, Agata Andrzejewska, Elżbieta Modrzejewska, Marcin Horecki, Konrad Jarosz and Jowita Biernawska

J. Pers. Med. 2023, 13(9), 1417; https://doi.org/10.3390/jpm13091417 - 21 Sep 2023

Cited by 1 | Viewed by 841

Abstract

The enhanced recovery after surgery (ERAS) protocol is not routine management in paediatric orthopaedics. Cultural differences or assumptions about the financing of medical care in different countries encourage creative adaptation of general assumptions in local communities. The aim of this study was to [...] Read more.

The enhanced recovery after surgery (ERAS) protocol is not routine management in paediatric orthopaedics. Cultural differences or assumptions about the financing of medical care in different countries encourage creative adaptation of general assumptions in local communities. The aim of this study was to compare the quality of the perioperative period before and after the introduction of an interdisciplinary protocol adopted to organisational conditions. A group of 4098 children were included in the “before–after” observational study. The data of 1553 patients (BEFORE group) were analysed in terms of compliance with the enhanced recovery after surgery protocol guidelines and the time and cost of hospitalisation over a 20-month period. A novel interdisciplinary protocol was developed, including an education and training app called BackOnFeet (BOF^®), standardised hospital management, and the introduction of methods novel to Poland (intraoperative nerve cryoanalgesia in children). A further 2545 patients (AFTER group) were reassessed over a period of 20 months. It was found that the groups differed in hospitalisation time (p < 0.001), type of procedures, and percentage ratio of costs incurred to revenue generated. The usefulness of the BOF^® app as an effective educational tool was demonstrated. The optimisation of perioperative management in paediatric orthopaedics based on novel tools and the interdisciplinary ERAS protocol is possible and brings tangible benefits in psychological, organisational, and financial terms. Full article

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13 pages, 279 KiB

Open AccessArticle

Hypertensive Disorders of Pregnancy: Assessing the Significance of Lp(a) and ApoB Concentrations in a Romanian Cohort

by Simona-Alina Abu-Awwad, Marius Craina, Lioara Boscu, Elena Bernad, Paula Diana Ciordas, Catalin Marian, Mircea Iurciuc, Ahmed Abu-Awwad, Stela Iurciuc, Brenda Bernad, Diana Maria Anastasiu Popov and Anca Laura Maghiari

J. Pers. Med. 2023, 13(9), 1416; https://doi.org/10.3390/jpm13091416 - 21 Sep 2023

Viewed by 973

Abstract

Background: This research delves into the association between altered lipid profiles and hypertensive disorders of pregnancy (HDP), shedding light on cardiovascular implications in maternal health. Methods: A cohort of 83 pregnant women was studied, with 48.19% diagnosed with HDP. This investigation [...] Read more.

Background: This research delves into the association between altered lipid profiles and hypertensive disorders of pregnancy (HDP), shedding light on cardiovascular implications in maternal health. Methods: A cohort of 83 pregnant women was studied, with 48.19% diagnosed with HDP. This investigation primarily focused on Apolipoprotein B (ApoB) and Lipoprotein(a) (Lp(a)) as indicators of cardiovascular health. A comparative examination was conducted to determine discrepancies in the ApoB and Lp(a) levels between standard pregnancies and those presenting with HDP. Results: Significant elevations in ApoB (p value = 0.0486) and Lp(a) (p value < 0.0001) levels were observed in pregnant women with HDP compared to their counterparts with typical pregnancies. The pronounced link between heightened ApoB and Lp(a) concentrations and HDP persisted, even considering pregnancy’s distinct physiological conditions. Conclusions: Our research accentuates the crucial role of early detection and specialized handling of cardiovascular risks in expectant mothers, especially those predisposed to HDP. The study indicates ApoB and Lp(a)’s potential as reliable markers for gauging cardiovascular threats during gestation. Furthermore, our findings suggest an integrative care approach and guidance for pregnant women, aspiring to enhance cardiovascular health in the postpartum phase. Full article

14 pages, 1591 KiB

Open AccessArticle

Effectiveness of Dry Needling versus Manual Therapy in Myofascial Temporomandibular Disorders: A Single-Blind Randomized Controlled Trial

by Rocío García-de la-Banda-García, Irene Cortés-Pérez, María del Rocío Ibancos-Losada, María del Carmen López-Ruiz, Esteban Obrero-Gaitán and María Catalina Osuna-Pérez

J. Pers. Med. 2023, 13(9), 1415; https://doi.org/10.3390/jpm13091415 - 21 Sep 2023

Cited by 1 | Viewed by 1432

Abstract

Dry needling (DN) is an invasive physiotherapy technique employed for reducing myofascial pain. To compare the effectiveness of dry needling (DN) versus manual therapy (MT) in improving pain, active maximal mouth opening (AMMO) and cervical disability in patients with myofascial pain from temporomandibular [...] Read more.

Dry needling (DN) is an invasive physiotherapy technique employed for reducing myofascial pain. To compare the effectiveness of dry needling (DN) versus manual therapy (MT) in improving pain, active maximal mouth opening (AMMO) and cervical disability in patients with myofascial pain from temporomandibular disorders (TMDs) were investigated against these treatments. A single-blind, randomized controlled trial was carried out. Individuals (n = 50) with TMDs were randomly allocated in a 1:1 ratio to the DN (n = 25) or MT group (n = 25). Each group received three sessions, separated by 4 days, of either DN or MT. Outcomes were assessed according to pain intensity (Numeric Pain Rating Scale), AMMO (cm), disability (Neck Disability Index), and pressure–pain threshold (PPT) (digital algometry) from the active myofascial trigger points. In both groups, pain and neck disability were significantly lower at the end of treatment compared with those measured at baseline (pain: −2.52 with 95% CI: −3.43 to −1.60 for DN group; pain: −2.92 with 95% CI: −3.77 to −2.07 for MT group; disability: −3.2 with 95% CI: −4.31 to −2.09 for DN group; disability: −2.68 with 95% CI: −3.56 to −1.79 for MT group), but not were not lower after the first session, without differences between the groups. AMMO was significantly higher after the first session (0.16 with 95% CI: 0.03 to 0.29 for DN group; 0.30 with 95% CI: 0.20 to 0.41 for MT group) and at the end of treatment in both groups (0.27 with 95% CI: 0.14 to 0.41 for DN group; 0.37 with 95% CI: 0.22 to 0.52 for MT group) compared with the baseline measurements. Finally, PPT results for the masseter and pterygoid muscles were significantly higher at the end of treatment in both groups (without statistically significant differences between groups), but not after the first session. The assessed therapies, DN and MT, are equally effective in improving pain, AMMO, cervical disability, and PPT in the muscles directly involved in the temporomandibular joint biomechanics of patients with myofascial TMDs. Full article

(This article belongs to the Special Issue Clinical Management of Chronic Pain: Personalized Approaches)

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12 pages, 796 KiB

Open AccessArticle

Association between Proteinuria Status and Risk of Hypertension: A Nationwide Population-Based Cohort Study

by Hyungwoo Lee, Moo-Suk Park, Min Kyoung Kang and Tae-Jin Song

J. Pers. Med. 2023, 13(9), 1414; https://doi.org/10.3390/jpm13091414 - 20 Sep 2023

Cited by 2 | Viewed by 1572

Abstract

Proteinuria is associated with cardiovascular disease. However, the relationship between changes in proteinuria status and hypertension remains unclear. This study aimed to explore the association between changes in proteinuria status and the risk of developing hypertension with the data from the Korean National [...] Read more.

Proteinuria is associated with cardiovascular disease. However, the relationship between changes in proteinuria status and hypertension remains unclear. This study aimed to explore the association between changes in proteinuria status and the risk of developing hypertension with the data from the Korean National Health Insurance Database. We included participants without prior hypertension history who underwent their first health examination in 2003–2004 and a second examination in 2005–2006. Based on their proteinuria status during these two examinations, participants were classified into four groups: the proteinuria-free, proteinuria-resolved, proteinuria-developed, and chronic proteinuria groups. The study outcome was the incidence of hypertension. The study included 935,723 participants followed for a median of 14.2 years (mean age: 40.96 ± 11.01, 62.5% male participants). During this period, 346,686 (37.1%) cases of hypertension were reported. The chronic proteinuria group had the highest hypertension risk, followed by the proteinuria-developed, proteinuria-resolved, and proteinuria-free groups (p < 0.001). Those who recovered from proteinuria had a lower risk of developing hypertension than those with chronic proteinuria (hazard ratio: 0.58; 95% confidence interval: 0.53–0.63, p < 0.001). In contrast, individuals who developed proteinuria had a higher risk of hypertension than proteinuria-free individuals (hazard ratio: 1.31; 95% confidence interval: 1.26–1.35, p < 0.001). Our findings suggest a significant association between proteinuria status changes and hypertension. Effective management of proteinuria may potentially decrease the risk of developing hypertension. Full article

(This article belongs to the Section Epidemiology)

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12 pages, 620 KiB

Open AccessReview

A Multifaced Aspect of Clostridium difficile Infection in Pediatric Patients with Inflammatory Bowel Disease: Case Series and Literature Review

by Elena Iana, Catalin Boboc, Andreea Gabriela Vlad, Maria Teodora Cosoreanu, Malina Anghel, Anca Andreea Boboc, Andreea Ioan, Mara Ioana Ionescu, Liana Gavriliu and Felicia Galos

J. Pers. Med. 2023, 13(9), 1413; https://doi.org/10.3390/jpm13091413 - 20 Sep 2023

Viewed by 1128

Abstract

Children with inflammatory bowel disease (IBD) have an increased susceptibility to Clostridium difficile infection (CDI), with a rising incidence over time. Differentiating between CDI and IBD exacerbation is challenging due to overlapping symptoms. In our cohort of 55 pediatric IBD patients, 6 were [...] Read more.

Children with inflammatory bowel disease (IBD) have an increased susceptibility to Clostridium difficile infection (CDI), with a rising incidence over time. Differentiating between CDI and IBD exacerbation is challenging due to overlapping symptoms. In our cohort of 55 pediatric IBD patients, 6 were diagnosed with CDI. Upon conducting a thorough patient evaluation and subsequent data analysis, an exhaustive review of the existing literature was undertaken. CDI is more prevalent in ulcerative colitis (UC) than Crohn’s disease (CD) patients, as seen in our patients and in the existing literature. The management of a pediatric patient with IBD is itself a challenge for a clinician because of the chronic, possibly relapsing course, and substantial long-term morbidity. When CDI is added, it becomes even more demanding, since CDI leads to more severe disease in children with IBD. A multidisciplinary approach and intensive treatment for possible sepsis, anemia, hypoalbuminemia, and hydro-electrolytic and acid-base imbalances are frequently mandatory in patients with CDI and IBD, which leads to a significant health care burden in hospitalized children with IBD. After the infection is treated with antibiotic therapy, important considerations regarding the future treatment for the underlying IBD are also necessary; in most cases, a treatment escalation is required, as also seen in our study group. Full article

(This article belongs to the Section Evidence Based Medicine)

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22 pages, 4224 KiB

Open AccessArticle

microRNA as a Maternal Marker for Prenatal Stress-Associated ASD, Evidence from a Murine Model

by Taeseon Woo, Candice King, Nick I. Ahmed, Madison Cordes, Saatvika Nistala, Matthew J. Will, Clark Bloomer, Nataliya Kibiryeva, Rocio M. Rivera, Zohreh Talebizadeh and David Q. Beversdorf

J. Pers. Med. 2023, 13(9), 1412; https://doi.org/10.3390/jpm13091412 - 20 Sep 2023

Cited by 1 | Viewed by 1000

Abstract

Autism Spectrum Disorder (ASD) has been associated with a complex interplay between genetic and environmental factors. Prenatal stress exposure has been identified as a possible risk factor, although most stress-exposed pregnancies do not result in ASD. The serotonin transporter (SERT) gene has been [...] Read more.

Autism Spectrum Disorder (ASD) has been associated with a complex interplay between genetic and environmental factors. Prenatal stress exposure has been identified as a possible risk factor, although most stress-exposed pregnancies do not result in ASD. The serotonin transporter (SERT) gene has been linked to stress reactivity, and the presence of the SERT short (S)-allele has been shown to mediate the association between maternal stress exposure and ASD. In a mouse model, we investigated the effects of prenatal stress exposure and maternal SERT genotype on offspring behavior and explored its association with maternal microRNA (miRNA) expression during pregnancy. Pregnant female mice were divided into four groups based on genotype (wildtype or SERT heterozygous knockout (Sert-het)) and the presence or absence of chronic variable stress (CVS) during pregnancy. Offspring behavior was assessed at 60 days old (PD60) using the three-chamber test, open field test, elevated plus-maze test, and marble-burying test. We found that the social preference index (SPI) of SERT-het/stress offspring was significantly lower than that of wildtype control offspring, indicating a reduced preference for social interaction on social approach, specifically for males. SERT-het/stress offspring also showed significantly more frequent grooming behavior compared to wildtype controls, specifically for males, suggesting elevated repetitive behavior. We profiled miRNA expression in maternal blood samples collected at embryonic day 21 (E21) and identified three miRNAs (mmu-miR-7684-3p, mmu-miR-5622-3p, mmu-miR-6900-3p) that were differentially expressed in the SERT-het/stress group compared to all other groups. These findings suggest that maternal SERT genotype and prenatal stress exposure interact to influence offspring behavior, and that maternal miRNA expression late in pregnancy may serve as a potential marker of a particular subtype of ASD pathogenesis. Full article

(This article belongs to the Special Issue A Personalized Medicine Approach to the Diagnosis and Management of Autism Spectrum Disorder: Beyond Genetic Syndromes)

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15 pages, 11873 KiB

Open AccessTechnical Note

Integrating Neuromonitoring in Pediatric Emergency Medicine: Exploring Two Options for Point-of-Care Electroencephalogram (pocEEG) via Patient Monitors—A Technical Note

by Leopold Simma, Fabrizio Romano, Steffen Schmidt, Georgia Ramantani and Bigna K. Bölsterli

J. Pers. Med. 2023, 13(9), 1411; https://doi.org/10.3390/jpm13091411 - 20 Sep 2023

Cited by 1 | Viewed by 1146

Abstract

Central nervous system (CNS) disorders are among the most frequent presentations in critically ill children. Status epilepticus (SE) is a frequent scenario in the resuscitation bay. In patients with altered mental status, non-convulsive SE (NCSE) is often underrecognized and critically impacts the neurological [...] Read more.

Central nervous system (CNS) disorders are among the most frequent presentations in critically ill children. Status epilepticus (SE) is a frequent scenario in the resuscitation bay. In patients with altered mental status, non-convulsive SE (NCSE) is often underrecognized and critically impacts the neurological outcome and duration of hospitalization. An electroencephalogram (EEG) is required to diagnose NCSE. However, standard EEG recordings are time- and staff-intensive, and their availability is limited, especially outside regular working hours. We aimed to improve patient care by developing a simplified EEG recording method, using a reduced lead montage (point-of-care EEG—pocEEG), that is suitable for use in pediatric emergency departments. The objective was to devise a cost-effective unit with low space requirements that fitted the existing technical infrastructure. We present two technical options for clinical pocEEG acquisition using patient monitors (GE Carescape, Philips IntelliVue) that enable data collection for educational and research purposes. A simplified, rapid response EEG like the pocEEG enables neuromonitoring of patients with CNS disorders in pediatric emergency settings, facilitating timely diagnosis and treatment initiation when standard EEG is not readily available. Full article

(This article belongs to the Special Issue Pediatric Neurology: Current Trends, Rehabilitation and Future Challenges)

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15 pages, 1517 KiB

Open AccessReview

New Community and Sociohealth Challenges Arising from the Early Diagnosis of Mild Cognitive Impairment (MCI)

by Carolina López and Miren Altuna

J. Pers. Med. 2023, 13(9), 1410; https://doi.org/10.3390/jpm13091410 - 20 Sep 2023

Viewed by 1130

Abstract

Population aging increases the risk of developing neurodegenerative diseases that cause cognitive impairment. Advances in clinical practice and greater social awareness of the importance of cognitive impairment have led to an increase in the number of people with early diagnosis, predementia. Increasing access [...] Read more.

Population aging increases the risk of developing neurodegenerative diseases that cause cognitive impairment. Advances in clinical practice and greater social awareness of the importance of cognitive impairment have led to an increase in the number of people with early diagnosis, predementia. Increasing access to biomarkers to assess whether Alzheimer’s disease (AD) is the underlying cause of mild cognitive impairment (MCI) has undoubted clinical benefits (access to potentially disease-modifying treatments, among others) but is also responsible for new social–health care challenges. Understanding the psychosocial impact of a diagnosis of MCI due to AD or another neurodegenerative disease is essential to create future strategies to reduce the emotional overload of patients, their risk of discrimination and stigmatization, and to favor their social inclusion. We present a narrative review of the diagnostic process of mild cognitive impairment in clinical practice, with a holistic person-centered approach, and discuss the implications of such diagnosis (benefits and risks) and strategies on how to address them. Full article

(This article belongs to the Section Mechanisms of Diseases)

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17 pages, 1947 KiB

Open AccessReview

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

by Youssef M. Roman

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

Cited by 2 | Viewed by 4049

Abstract

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

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

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15 pages, 553 KiB

Open AccessArticle

Systemic Inflammatory Response Index (SIRI) at Baseline Predicts Clinical Response for a Subset of Treatment-Resistant Bipolar Depressed Patients

by Stephen Murata, Nausheen Baig, Kyle Decker and Angelos Halaris

J. Pers. Med. 2023, 13(9), 1408; https://doi.org/10.3390/jpm13091408 - 20 Sep 2023

Cited by 1 | Viewed by 915

Abstract

Background: in a recent double-blind, placebo controlled RCT we demonstrated that selective inhibition of cyclo-oxygenase 2 (COX2) is an effective adjunctive strategy in treatment-resistant bipolar depression (TRBDD). To better clarify the mechanisms underlying TRBDD and treatment response, we conducted a retrospective exploratory [...] Read more.

Background: in a recent double-blind, placebo controlled RCT we demonstrated that selective inhibition of cyclo-oxygenase 2 (COX2) is an effective adjunctive strategy in treatment-resistant bipolar depression (TRBDD). To better clarify the mechanisms underlying TRBDD and treatment response, we conducted a retrospective exploratory analysis of the systemic inflammatory response index (SIRI = absolute neutrophils × absolute monocytes/absolute lymphocytes) in relation to other biomarkers and clinical outcomes after escitalopram (ESC), combined with the COX-2 inhibitor, celecoxib (CBX), versus placebo. Methods: Baseline measures of SIRI were compared between TRBDD and healthy controls (HC), and correlated with blood-based inflammatory cytokines, kynurenines, and growth factors. Post-treatment Hamilton Depression Rating Scale 17 (HAMD-17) total scores (clinical outcome) were modelled according to SIRI adjusting for demographics (including relevant interactions with SIRI), baseline depression, treatment arm, and treatment timepoint using multiple linear regression and robust linear mixed effects models. Results: Baseline SIRI did not distinguish TRBDD from HC groups. Baseline SIRI was significantly correlated with lower baseline MCP-1. The relationship between SIRI and HAMD-17 was significant at treatment week 8, in contrast to baseline. Finally, baseline SIRI predicted elevated post-treatment HAMD-17 scores, amongst patients with elevated depression scores at baseline. Significance: High pre-treatment SIRI may predict poorer depressive outcomes amongst TRBDD patients with baseline elevated depression. Full article

(This article belongs to the Special Issue Pharmacogenomics and Precision Medicine in Psychiatry: From Basic Research to Clinical Practice)

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10 pages, 894 KiB

Open AccessArticle

Return of Participants’ Incidental Genetic Research Findings: Experience from a Case-Control Study of Asthma in an American Indian Community

by Lyle G. Best, Marcia O’Leary, Rae O’Leary, Wendy Lawrence and Dara G. Torgerson

J. Pers. Med. 2023, 13(9), 1407; https://doi.org/10.3390/jpm13091407 - 20 Sep 2023

Viewed by 814

Abstract

The proper communication of clinically actionable findings to participants of genetic research entails important ethical considerations, but has been challenging for a variety of reasons. We document an instance of the return of individual genetic results in the context of a very rural [...] Read more.

The proper communication of clinically actionable findings to participants of genetic research entails important ethical considerations, but has been challenging for a variety of reasons. We document an instance of the return of individual genetic results in the context of a very rural American Indian community, in hopes of providing insight to other investigators about potentially superior or inferior courses of action. This was a case/control study of asthma among 324 pediatric participants. Subsequently, microarray genotype data became available, providing over 2 million variants, incidentally including some conferring risk for conditions for which the American College of Medical Genetics recommends return of results. The study investigators engaged in extensive consultation with the IRB, the tribal government, and local clinicians to better inform our approach. We were able to notify the two participants heterozygous for the one clinically actionable variant identified. One participant welcomed this information and proceeded to obtain further clinical work-up; the other participant declined further follow-up. While demanding considerable time and effort, the return of clinically actionable genetic results is important from both an ethical perspective and to provide an improved trust relationship with the community of research participants. Full article

(This article belongs to the Section Omics/Informatics)

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9 pages, 853 KiB

Open AccessArticle

The Association between Hip Joint Morphology and Posterior Wall Fracture: Analysis of Radiologic Parameters in Computed Tomography

by Han Soul Kim, Ki Uk Mun and Chul-Ho Kim

J. Pers. Med. 2023, 13(9), 1406; https://doi.org/10.3390/jpm13091406 - 20 Sep 2023

Viewed by 970

Abstract

Although numerous radiologic parameters of abnormal hip joint morphology are utilized in practice, studies on the relation of these parameters to acetabular fractures are limited. This study hypothesized that certain morphological features of hip joints are associated with acetabular posterior wall (PW) fracture [...] Read more.

Although numerous radiologic parameters of abnormal hip joint morphology are utilized in practice, studies on the relation of these parameters to acetabular fractures are limited. This study hypothesized that certain morphological features of hip joints are associated with acetabular posterior wall (PW) fracture patterns and aimed to identify morphological characteristics predictive of acetabular PW fracture. The records of 107 consecutive patients, who were diagnosed with acetabular fractures in a level I trauma center from August 2017 to April 2021, were initially reviewed. After excluding patients who lacked proper radiographic evaluation and had previous surgery or concomitant injury on the ipsilateral lower limb, a total of 99 patients were analyzed to investigate the morphological characteristics of the hip joint, measured in computed tomography, associated with acetabular posterior wall fracture. We included patient demographics, acetabular index (AI), sharp angle, acetabular depth-to-width ratio (AD/WR), center-edge angle (CEA), head–neck offset ratio (HNOR), acetabular head index (AHI), anterior acetabular sector angle (AASA), posterior acetabular sector angle (PASA), and acetabular version angle (AVA) in the univariate and multivariate analyses. The injury mechanism (p = 0.001) and AD/WR (p = 0.021) were predictors of PW fracture in the univariate analysis. In the multivariable analysis, injury mechanism (p = 0.011), AI (coefficient B = 0.320; Exp (B) = 1.377; p = 0.017), and AD/WR (coefficient B = 33.047; Exp (B) = 2.250 × 10¹⁴; p = 0.028) were significant predictors of PW fracture. This study highlights the importance of morphological factors, such as a larger AI and AD/WR, that may influence joint stress distribution, resulting in acetabular PW fracture. Understanding these pathomechanisms may protect the hip joint and prevent future injuries through the early identification and treatment of pathological conditions. Full article

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

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12 pages, 2496 KiB

Open AccessArticle

Interdisciplinary Treatment of Malignant Chest Wall Tumors

by Koblandy Khamitov, Wojciech Dudek, Andreas Arkudas, Mohamed Haj Khalaf, Chirag Parjiea, Mostafa Higaze, Raymund E. Horch and Horia Sirbu

J. Pers. Med. 2023, 13(9), 1405; https://doi.org/10.3390/jpm13091405 - 20 Sep 2023

Viewed by 1161

Abstract

Background: Chest wall resections for malignant chest wall tumors (MCWTs), particularly those with full-thickness chest wall involvement requiring reconstruction, present a therapeutic challenge for thoracic and plastic reconstructive surgeons. The purpose of this study was to review our experience with chest wall resection [...] Read more.

Background: Chest wall resections for malignant chest wall tumors (MCWTs), particularly those with full-thickness chest wall involvement requiring reconstruction, present a therapeutic challenge for thoracic and plastic reconstructive surgeons. The purpose of this study was to review our experience with chest wall resection for primary and metastatic MCWTs, with a focus on perioperative outcomes and postoperative overall survival (OS). Methods: All patients who underwent surgical resection for primary and secondary MCWTs at our single institution between 2000 and 2019 were retrospectively analyzed. Results: A total of 42 patients (25 male, median age 60 years) operated upon with curative (n = 37, 88.1%) or palliative (n = 5, 11.9%) intent were reviewed. Some 33 (78%) MCWTs were of secondary origin. Chest wall reconstruction was required in 40 (95%) cases. A total of 13 (31%) patients had postoperative complications and one (2.3%) died perioperatively. The 5-year postoperative overall survival rate was 51.9%. The postoperative 5-year survival rate of 42.6% in patients with secondary MCWTs was significantly lower compared to the figure of 87.5% in patients with primary MCWTs. Conclusions: In well-selected patients, chest wall resections for primary and secondary MCWTs are feasible and associated with good perioperative outcomes. For secondary MCWTs, surgery can also be performed with palliative intent. Full article

(This article belongs to the Special Issue Plastic and Reconstructive Surgery in Personalized Medicine: 2nd Edition)

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13 pages, 2325 KiB

Open AccessArticle

Targeting IL-4 and IL-13 Receptors on Eosinophils in CRSwNP Patients: The Clinical Efficacy of Dupilumab

by Giovanna Lucia Piazzetta, Nadia Lobello, Emanuela Chiarella, Alberta Rizzuti, Corrado Pelaia, Girolamo Pelaia and Nicola Lombardo

J. Pers. Med. 2023, 13(9), 1404; https://doi.org/10.3390/jpm13091404 - 19 Sep 2023

Cited by 2 | Viewed by 1305

Abstract

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory disease linked to type 2 inflammation. Several biologics have demonstrated therapeutic potential for the treatment of this pathology in which IL-4, IL-5 and IL-13 represent the major cytokines involved in the control of eosinophilic [...] Read more.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory disease linked to type 2 inflammation. Several biologics have demonstrated therapeutic potential for the treatment of this pathology in which IL-4, IL-5 and IL-13 represent the major cytokines involved in the control of eosinophilic respiratory inflammation. 25% of CRSwNP patients relapse after the use of oral glucocorticoids or after surgery and often require several surgeries during their lifetime. In our study we enrolled 14 patients, 11 male and 3 female. The inclusion criteria were: age ≥ 18 years; confirmed diagnosis of chronic rhinosinusitis with severe nasal polyposis; disease severity with NPS Nasal Polyposis Endoscopic Score total score ≥ 5 and/or SNOT-22 ≥ 50; previous treatment failure due to lack of efficacy or discontinuation of systemic corticosteroid therapy and/or non-response or recurrence following surgery. The results presented in this study showed the ability of Dupilumab to improve all the parameters analysed. In particular, statistically significant data were obtained for NPS, SNOT-22, NRS, and IgE in patients exposed to Dupilumab treatment for 24 weeks, highlighting the ability of Dupilumab to produce clinical benefit in CRWwNP patients. In light of these data, the administration of dupilumab every two weeks represents a valid clinical strategy that ENT specialists can adopt for the treatment of adults with inadequately controlled CRSwNP. Full article

(This article belongs to the Special Issue Recent Advances in Diagnosis, Treatment and Observation in Otorhinolaryngology)

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10 pages, 514 KiB

Open AccessArticle

Triglycerides, Obesity and Education Status Are Associated with the Risk of Developing Type 2 Diabetes in Young Adults, Cohort Study

by Evgeniia V. Garbuzova, Lilia V. Shcherbakova, Oksana D. Rymar, Alyona D. Khudiakova, Victoria S. Shramko and Yulia I. Ragino

J. Pers. Med. 2023, 13(9), 1403; https://doi.org/10.3390/jpm13091403 - 19 Sep 2023

Cited by 1 | Viewed by 761

Abstract

Background: It is important to determine the influence of traditional risk factors on the development of type 2 diabetes mellitus (T2DM) in young adults. Goal of the research: To study the incidence of T2DM and factors that increase the risk of its occurrence [...] Read more.

Background: It is important to determine the influence of traditional risk factors on the development of type 2 diabetes mellitus (T2DM) in young adults. Goal of the research: To study the incidence of T2DM and factors that increase the risk of its occurrence during the observation of a cohort of young adults. Materials and methods: 1341 people aged 25–44 were included in the study from 2013 to 2017, of whom 622 were men (46.4%). The examination included anamnesis, anthropometric data, and a blood test. Cases of developed T2DM were identified by comparing the Diabetes Mellitus Register, medical records of patients, and the database of examined individuals from 2019 to 2023. T2DM Results: In the examined population, 11 participants (0.82%) developed T2DM. The prevalence of T2DM was 0.96% in men and 0.69% in women. Patients with T2DM had a higher waist circumference, BMI, SBP, TG, and lower HDL than patients without T2DM, and were also less likely to have a higher education. The risk of developing T2DM increases 6.5 times at a BMI of ≥30 kg/m², and 5.2 times at a TG level of ≥1.7 mmol/L, regardless of other risk factors. In the absence of a higher education, the risk of developing T2DM is increased by 5.6 times. Conclusion: In young people, high triglyceride levels, obesity, and a low level of education are associated with the risk of developing type 2 diabetes, regardless of other factors. Full article

(This article belongs to the Special Issue Selected Papers from the 2nd Conference with International Participation “Basic Research in Endocrinology: A Modern Strategy for the Development and Technologies of Personalized Medicine”)

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13 pages, 3265 KiB

Open AccessArticle

Clinical Efficacy Analysis of the Personalization of Prosthetic Abutments in Implant Supported Restorations in Comparison to Available Standard Titanium Abutments

by Magdalena Eugenia Obădan, Ioana Mitruț, Mihaela Ionescu, Florian Obădan, Daniel Adrian Târtea, Marcel Adrian Popescu, Sanda Mihaela Popescu, Andreea Maria Smarandache and Horia Octavian Manolea

J. Pers. Med. 2023, 13(9), 1402; https://doi.org/10.3390/jpm13091402 - 19 Sep 2023

Viewed by 944

Abstract

Personalized medicine has become an important direction to offer better solutions for health problems. In implantology, this trend was materialized through customizing dental abutments to each clinical situation. The demands for better esthetics and function of implant-supported restorations have imposed a more personalized [...] Read more.

Personalized medicine has become an important direction to offer better solutions for health problems. In implantology, this trend was materialized through customizing dental abutments to each clinical situation. The demands for better esthetics and function of implant-supported restorations have imposed a more personalized variety of prosthetic abutments. This retrospective study compared clinical efficiency of personalized implant abutments with standard implant abutments in multiple implant restorations. Clinical data of patients who were admitted in a private clinic between 2011 and 2022 and received dental implant treatments were collected. All complications and undesired events from the patients’ medical record charts were statistically analyzed. The implants were loaded using either standard or customized abutments. For complete arch rehabilitations with the SKY Fast & Fixed protocol, standard titanium prosthetic abutments were used. Our results suggest that the abutments choice for patients has moved throughout the years more towards the use of customized abutments. The number of customized abutments (414) was higher compared with the number of standard abutments (293). In our database, the most used abutments for the anterior area implants were made of titanium and zirconia, whereas for the posterior area, the preferred abutments were mostly titanium. The standard abutments were used almost entirely for immediate loading and implantation in both anterior and posterior areas (Fast & Fixed protocol). Complications were encountered mainly in restorations with standard abutments (9.22%) compared to customized abutments (2.7%), with titanium abutments being the most reliable, having only 1.79% complications. Full article

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14 pages, 2925 KiB

Open AccessArticle

Development and Validation of an XGBoost-Algorithm-Powered Survival Model for Predicting In-Hospital Mortality Based on 545,388 Isolated Severe Traumatic Brain Injury Patients from the TQIP Database

by Yang Cao, Maximilian Peter Forssten, Babak Sarani, Scott Montgomery and Shahin Mohseni

J. Pers. Med. 2023, 13(9), 1401; https://doi.org/10.3390/jpm13091401 - 19 Sep 2023

Viewed by 868

Abstract

Background: Traumatic brain injury (TBI) represents a significant global health issue; the traditional tools such as the Glasgow Coma Scale (GCS) and Abbreviated Injury Scale (AIS) which have been used for injury severity grading, struggle to capture outcomes after TBI. Aim and methods: [...] Read more.

Background: Traumatic brain injury (TBI) represents a significant global health issue; the traditional tools such as the Glasgow Coma Scale (GCS) and Abbreviated Injury Scale (AIS) which have been used for injury severity grading, struggle to capture outcomes after TBI. Aim and methods: This paper aims to implement extreme gradient boosting (XGBoost), a powerful machine learning algorithm that combines the predictions of multiple weak models to create a strong predictive model with high accuracy and efficiency, in order to develop and validate a predictive model for in-hospital mortality in patients with isolated severe traumatic brain injury and to identify the most influential predictors. In total, 545,388 patients from the 2013–2021 American College of Surgeons Trauma Quality Improvement Program (TQIP) database were included in the current study, with 80% of the patients used for model training and 20% of the patients for the final model test. The primary outcome of the study was in-hospital mortality. Predictors were patients’ demographics, admission status, as well as comorbidities, and clinical characteristics. Penalized Cox regression models were used to investigate the associations between the survival outcomes and the predictors and select the best predictors. An extreme gradient boosting (XGBoost)-powered Cox regression model was then used to predict the survival outcome. The performance of the models was evaluated using the Harrell’s concordance index (C-index). The time-dependent area under the receiver operating characteristic curve (AUC) was used to evaluate the dynamic cumulative performance of the models. The importance of the predictors in the final prediction model was evaluated using the Shapley additive explanations (SHAP) value. Results: On average, the final XGBoost-powered Cox regression model performed at an acceptable level for patients with a length of stay up to 250 days (mean time-dependent AUC = 0.713) in the test dataset. However, for patients with a length of stay between 20 and 213 days, the performance of the model was relatively poor (time-dependent AUC < 0.7). When limited to patients with a length of stay ≤20 days, which accounts for 95.4% of all the patients, the model achieved an excellent performance (mean time-dependent AUC = 0.813). When further limited to patients with a length of stay ≤5 days, which accounts for two-thirds of all the patients, the model achieved an outstanding performance (mean time-dependent AUC = 0.917). Conclusion: The XGBoost-powered Cox regression model can achieve an outstanding predictive ability for in-hospital mortality during the first 5 days, primarily based on the severity of the injury, the GCS on admission, and the patient’s age. These variables continue to demonstrate an excellent predictive ability up to 20 days after admission, a period of care that accounts for over 95% of severe TBI patients. Past 20 days of care, other factors appear to be the primary drivers of in-hospital mortality, indicating a potential window of opportunity for improving outcomes. Full article

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

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15 pages, 1817 KiB

Open AccessArticle

Complement System Proteins in the Human Aqueous Humor and Their Association with Primary Open-Angle Glaucoma

by Ayushi Vashishtha, Sharon W. Maina, Jeremy Altman, Garrett Jones, Tae Jin Lee, Kathryn E. Bollinger, Lane Ulrich, Marc Töteberg-Harms, Amy J. Estes, Wenbo Zhi, Shruti Sharma and Ashok Sharma

J. Pers. Med. 2023, 13(9), 1400; https://doi.org/10.3390/jpm13091400 - 19 Sep 2023

Cited by 1 | Viewed by 1080

Abstract

This study discovers the complement protein profile in the aqueous humor (AH) of human subjects and investigates its association with primary open-angle glaucoma (POAG) pathogenesis. Among the 32 complement proteins identified, 22 were highly abundant and detected in more than 50% of AH [...] Read more.

This study discovers the complement protein profile in the aqueous humor (AH) of human subjects and investigates its association with primary open-angle glaucoma (POAG) pathogenesis. Among the 32 complement proteins identified, 22 were highly abundant and detected in more than 50% of AH samples. The most predominant active complement proteins in the AH are C3, C4B, C4A, CFB, CFD, and C9. Additionally, the most prevalent complement regulators and receptors include CLU, SERPING1, F2, CFH, CFI, and VTN. Significant alterations in complement proteins were observed in individuals with POAG compared to those with cataracts. Specifically, complement protein F2 was upregulated, while C8G, C6, and CFH were downregulated in POAG samples. Stratification of the samples by race and sex revealed distinct alterations of complement proteins in patients with POAG. In the African American cohort, five complement proteins (C4A, C4B, F2, C7, and C3) were upregulated in POAG compared to cataract patients. In the Caucasian cohort, eight complement proteins (C3, SERPING1, CFI, CLU, CFHR1, C8G, C6, and CFH) were downregulated in the POAG samples compared to the cataract samples. Within the male cohort, three complement proteins (CLU, C6, and CFH) were downregulated in POAG patients compared to those with cataracts. Whereas, within the female cohort, two complement proteins (C4B and F2) were upregulated and one (C8G) downregulated in the POAG samples when compared to cataracts. Discerning these changes in the AH complement protein profile will assist in the development of tailored therapies to modulate the complement system for managing ocular disorders. These insights may also lead to novel biomarkers for diagnosing and monitoring disease progression. Full article

(This article belongs to the Special Issue Recent Advances and Clinical Research in Glaucoma)

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11 pages, 4672 KiB

Open AccessArticle

Effect of Radiation Therapy on Composition of Lymphocyte Populations in Patients with Primary Breast Cancer

by Irina Kobzeva, Tatiana Astrelina, Yuliya Suchkova, Tatyana Malivanova, Daria Usupzhanova, Vitaliy Brunchukov, Anna Rastorgueva, Victoria Nikitina, Ekaterina Lubaeva, Marina Sukhova, Alexey Kirilchev, Tatyana Butkova, Alexander Izotov, Kristina Malsagova, Alexander Samoilov and Vasiliy Pustovoyt

J. Pers. Med. 2023, 13(9), 1399; https://doi.org/10.3390/jpm13091399 - 19 Sep 2023

Viewed by 904

Abstract

Background: Radiation therapy (RT) is an important step in the treatment of primary breast cancer as it is one of the leading contributors to cancer incidence among women. Most patients with this disease acquire radiation-induced lymphopenia in the early post-radiation period; however, little [...] Read more.

Background: Radiation therapy (RT) is an important step in the treatment of primary breast cancer as it is one of the leading contributors to cancer incidence among women. Most patients with this disease acquire radiation-induced lymphopenia in the early post-radiation period; however, little is known about the effect of RT on the composition of lymphocyte populations in such patients. This study was aimed at investigating the effect of adjuvant remote RT—performed in the classical mode for patients with primary breast cancer—on the main components of cell-mediated immunity (major lymphocyte populations), including those in patients receiving chemotherapy. Methods: Between 2020 and 2022, 96 patients with stage I–III breast cancer were included in this study. All patients in the final stage of complex treatment received RT via a 3D conformal technique (3DCRT). The clinical target volume of this RT included the breast or chest wall and locoregional lymphatics. Flow cytometry was used to assess the levels and phenotypes of circulating lymphocytes before and after RT (no more than 7 days before and after RT). The evaluation of the impact of polychemotherapy (PCT) was conducted to determine whether it was a risk factor for the onset of radio-induced lymphopenia (RIL) in the context of RT. Results: When assessing the immune status in the general group of patients (n = 96), before the start of adjuvant external beam radiotherapy (EBRT), the average number of lymphocytes was 1.68 ± 0.064 × 10⁹/L; after the course of adjuvant EBRT, it decreased to 1.01 ± 0.044 × 10⁹/L (p < 0.001). When assessing the absolute indicators of cellular immunity in the general group of patients with BC after a course of adjuvant EBRT, significant dynamics were revealed by the changes in all cell populations of lymphocytes (paired t-test, p < 0.05). Conclusion: The adaptive immune system in breast cancer patients changed in the early post-radiation period. The absolute levels of B-, T- and natural killer cells significantly reduced after RT regardless of whether the patients previously underwent chemotherapy courses. RT for patients with primary breast cancer should be considered in clinical management because it significantly alters lymphocyte levels and should be considered when assessing antitumor immunity, as significant changes in T-cell immunity have been observed. In addition, the identified changes are critical if specific targeted therapy or immunotherapy is needed. Full article

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

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14 pages, 2803 KiB

Open AccessArticle

A Novel Sensor-Based Application for Home-Based Rehabilitation Can Objectively Measure Postoperative Outcomes following Anterior Cruciate Ligament Reconstruction

by Natalie Mengis, Sebastian Schmidt, Andree Ellermann, Christian Sobau, Christian Egloff, Mahli Megan Kreher, Korbinian Ksoll, Caroline Schmidt-Lucke and Jules-Nikolaus Rippke

J. Pers. Med. 2023, 13(9), 1398; https://doi.org/10.3390/jpm13091398 - 19 Sep 2023

Cited by 1 | Viewed by 950

Abstract

In order to successfully implement individualized patient rehabilitation and home-based rehabilitation programs, the rehabilitation process should be objectifiable, monitorable and comprehensible. For this purpose, objective measurements are required in addition to subjective measurement tools. Thus, the aim of this prospective, single-center clinical trial [...] Read more.

In order to successfully implement individualized patient rehabilitation and home-based rehabilitation programs, the rehabilitation process should be objectifiable, monitorable and comprehensible. For this purpose, objective measurements are required in addition to subjective measurement tools. Thus, the aim of this prospective, single-center clinical trial is the clinical validation of an objective, digital medical device (DMD) during the rehabilitation after anterior cruciate ligament reconstruction (ACLR) with regards to an internationally accepted measurement tool. Sixty-seven patients planned for primary ACLR (70:30% male–female, aged 25 years [21–32], IKDC-SKF 47 [31–60], Tegner Activity Scale 6 [4–7], Lysholm Score 57 [42–72]) were included and received physical therapy and the DMD after surgery. For clinical validation, combined measures of range of motion (ROM), coordination, strength and agility were assessed using the DMD in addition to patient-reported outcome measures (PROMs) at three and six months after ACLR. Significant correlations were detected for ROM (rs = 0.36–0.46, p < 0.025) and strength/agility via the single-leg vertical jump (rs = 0.43, p = 0.011) and side hop test (rs = 0.37, p = 0.042), as well as for coordination via the Y-Balance test (rs = 0.58, p ≤ 0.0001) regarding the IKDC-SKF at three months. Additionally, DMD test results for coordination, strength and agility (Y-Balance test (rs = 0.50, p = 0.008), side hop test (rs = 0.54, p = 0.004) and single-leg vertical jump (rs = 0.44, p = 0.018)) correlate significantly with the IKDC-SKF at six months. No adverse events related to the use of the sensor-based application were reported. These findings confirm the clinical validity of a DMD to objectively quantify knee joint function for the first time. This will have further implications for clinical and therapeutic decision making, quality control and monitoring of rehabilitation measures as well as scientific research. Full article

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

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32 pages, 1177 KiB

Open AccessReview

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

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

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

Cited by 2 | Viewed by 1260

Abstract

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

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

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

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16 pages, 2329 KiB

Open AccessFeature PaperArticle

C9ORF72 Gene GGGGCC Hexanucleotide Expansion: A High Clinical Variability from Amyotrophic Lateral Sclerosis to Frontotemporal Dementia

by Izaro Kortazar-Zubizarreta, Africa Manero-Azua, Juan Afonso-Agüera and Guiomar Perez de Nanclares

J. Pers. Med. 2023, 13(9), 1396; https://doi.org/10.3390/jpm13091396 - 19 Sep 2023

Cited by 1 | Viewed by 1421

Abstract

The expanded GGGGCC hexanucleotide repeat (HRE) in the non-coding region of the C9ORF72 gene (C9ORF72-HRE) is the most common genetic cause of familial forms of amyotrophic lateral sclerosis (ALS), FTD, and concurrent ALS and FTD (ALS-FTD), in addition to contributing to the sporadic [...] Read more.

The expanded GGGGCC hexanucleotide repeat (HRE) in the non-coding region of the C9ORF72 gene (C9ORF72-HRE) is the most common genetic cause of familial forms of amyotrophic lateral sclerosis (ALS), FTD, and concurrent ALS and FTD (ALS-FTD), in addition to contributing to the sporadic forms of these diseases. Both syndromes overlap not only genetically, but also sharing similar clinical and neuropathological findings, being considered as a spectrum. In this paper we describe the clinical-genetic findings in a Basque family with different manifestations within the spectrum, our difficulties in reaching the diagnosis, and a narrative review, carried out as a consequence, of the main features associated with C9ORF72-HRE. Family members underwent a detailed clinical assessment, neurological examination, and genetic analysis by repeat-primed PCR. We studied 10 relatives of a symptomatic carrier of the C9ORF72-HRE expansion. Two of them presented the expansion in the pathological range, one of them was symptomatic whereas the other one remained asymptomatic at 72 years. Given the great intrafamilial clinical variability of C9ORF72-HRE, the characterization of patients and family members with particular clinical and genetic subgroups within ALS and FTD becomes a bottleneck for medication development, in particular for genetically focused medicines for ALS and FTD. Full article

(This article belongs to the Section Mechanisms of Diseases)

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Open AccessReview

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

by Anton Shkundin and Angelos Halaris

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

Cited by 2 | Viewed by 1808

Abstract

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

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

(This article belongs to the Section Disease Biomarker)

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J. Pers. Med., Volume 13, Issue 9 (September 2023) – 142 articles

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