J. Clin. Med., Volume 12, Issue 16 (August-2 2023) – 269 articles

Introduction: The primary objective of researchers in the biology of aging is to gain a comprehensive understanding of the aging process while developing practical solutions that can enhance the quality of life for older individuals. This involves a continuous effort to bridge the gap between fundamental biological research and its real-world applications. Purpose: In this narrative review, we attempt to link research findings concerning the hormetic relationship between neurons and germ cells, and translate these findings into clinically relevant concepts. Methods: We conducted a literature search using PubMed, Embase, PLOS, Digital Commons Network, Google Scholar and Cochrane Library from 2000 to 2023, analyzing studies dealing with the relationship between hormetic, cognitive, and reproductive aspects of human aging. Results: The process of hormesis serves as a bridge between the biology of neuron-germ cell interactions on one hand, and the clinical relevance of these interactions on the other. Details concerning these processes are discussed here, emphasizing new research which strengthens the overall concept. Conclusions: This review presents a scientifically and clinically relevant argument, claiming that maintaining a cognitively active lifestyle may decrease age-related degeneration, and improve overall health in aging. This is a totally novel approach which reflects current developments in several relevant aspects of our biology, technology, and society. Full article

The use of radiomics and artificial intelligence applied for the diagnosis and monitoring of Alzheimer’s disease has developed in recent years. However, this approach is not yet completely applicable in clinical practice. The aim of this paper is to provide a systematic analysis of the studies that have included the use of radiomics from different imaging techniques and artificial intelligence for the diagnosis and monitoring of Alzheimer’s disease in order to improve the clinical outcomes and quality of life of older patients. A systematic review of the literature was conducted in February 2023, analyzing manuscripts and articles of the last 5 years from the PubMed, Scopus and Embase databases. All studies concerning discrimination among Alzheimer’s disease, Mild Cognitive Impairment and healthy older people performing radiomics analysis through machine and deep learning were included. A total of 15 papers were included. The results showed a very good performance of this approach in the differentiating Alzheimer’s disease patients—both at the dementia and pre-dementia phases of the disease—from healthy older people. In summary, radiomics and AI can be valuable tools for diagnosing and monitoring the progression of Alzheimer’s disease, potentially leading to earlier and more accurate diagnosis and treatment. However, the results reported by this review should be read with great caution, keeping in mind that imaging alone is not enough to identify dementia due to Alzheimer’s. Full article

The aim of this study was to investigate the association between cognitive function and depressive symptoms in older couples while also examining the relationship between cognitive performance and the frequency of contact with adult children. A total of 96 couples volunteered for this study and provided their informed consent at enrollment. Participants completed a neuropsychological test battery consisting of five cognitive domains: attention, language and related functions, visuospatial functions, memory, and frontal/executive functions. Symptoms of depression were assessed using the short version of the Geriatric Depression Scale. The number of contacts with children was categorized into ≥1 per month and <1 per month. We found that the cognitive functions of husbands with depressed wives were significantly lower in the frontal/executive functions. In contrast, the wives’ cognitive performance was not associated with the husbands’ depressive symptoms. For couples who had contact with their adult children less than once a month, the odds of the husbands with lower cognitive performance were significantly higher, which was reflected in their scores in visuospatial and executive functions. Among older married couples, the cognitive functions of husbands may be influenced more by their wives’ mental health and degree of contact with their adult children. This infers that wives and offspring may act as a buffer against the cognitive impairment of older married men. Full article

The lipid profile is affected following menstrual cessation (MC). We aimed to evaluate the effects of goserelin-induced MC and subsequent menstrual restoration (MR) on lipid metabolism. Premenopausal women with histologically verified endometriosis (n = 15) received goserelin monthly for 6 months (6mο), resulting in MC, and were followed-up for another 6 months after MR (12mο). Serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein a ([Lp(a)] and lipidomics were measured at baseline, 6mo and 12mo. Shotgun quantitative deep lipidomics were determined at the level of lipid class category, subclass, species, and fatty acyl chain lengths and degree of saturation. TC (p = 0.006), LDL-C (p = 0.028), HDL-C (p = 0.002), and apoA1 (p = 0.013) increased during goserelin-induced MC and remained practically unchanged during MR. TG, apoB, and Lp(a) did not change. From the deep lipidomics analysis, multivariate statistical analysis demonstrated profound alterations in lipid species with MC, whereas no statistically valid models could be fitted for the restoration period. In conclusion, GnRH-analog-induced MC alters lipid profiles at various levels, from standard blood lipid and lipoprotein profiles to several lipid species as detected by lipidomics analysis. Changes largely persist for at least 6 m after MR. Full article

Bariatric surgery is increasingly used in women of childbearing age due to the rising prevalence of obesity and the effectiveness and availability of this treatment. Pregnancy in women with previous bariatric surgery deserves special attention. Weight loss induced by surgery reduces the risks that obesity poses to pregnancy. But on the other hand, decreased intake and malabsorption may increase the risk of malnutrition and micronutrient deficiency and negatively affect maternal and foetal health. The aim of this narrative review is to provide an updated analysis of the impact of different bariatric surgery techniques on mineral and micronutrient nutritional status during pregnancy and the possible effect on maternal–foetal health. Full article

The Crohn’s Disease (CD) exclusion diet (CDED) has been shown to induce remission in pediatric and adult patients with CD. In this retrospective cohort study, we describe our real-world experience with the CDED at the inflammatory bowel disease (IBD) unit of the Tel Aviv Medical Center between 2018–2021. CD patients with multiple clinical presentations and disease phenotypes who initiated the diet were included. Indications for treatment, medical and nutritional data were collected from dietician clinic visits and medical records. Clinical and biomarker responses were determined. The CDED was recommended to 220 CD patients. Seventy-two patients were included in the analysis for a clinically active disease (n = 48) or for remission maintenance (n = 24). Among patients with a clinically active disease, 62.5% of patients achieved clinical remission at week 6 and at week 12. A positive association between high adherence to the CDED and clinical remission at week 12 was observed (adjusted OR = 7.6, 95% CI 1.07–55.2, p = 0.043). Among patients treated for remission maintenance, remission at week 12 was maintained among 83.3% of patients. We conclude that the CDED may be a promising intervention for multiple CD presentations and indications. These findings should be further validated in larger, prospective, controlled studies. Full article

Background: Persistent inflammation, immunosuppression, and catabolism syndrome (PIICS) is known as a prolonged immunodeficiency that occurs after severe infection. Few studies have demonstrated a direct relationship between PIICS and physical dysfunction in post-intensive care syndrome (PICS). We herein investigated how each component of PICS was affected by the diagnosis of PIICS during hospitalization and examined the relationship between PIICS and PICS using PICS assessments performed at the Hitachi General Hospital PICS Clinic. Methods: The 273 patients who visited the PICS clinic at one month after discharge from the ICU at Hitachi General Hospital were included in the study. We used the diagnostic criteria for PIICS described in previous studies. At least two of the following blood test values on day 14 of hospitalization had to be met for a diagnosis of PIICS: C-reactive protein (CRP) > 2.0 mg/dL, albumin (Alb) < 3.0 g/dL, and lymphocytes (Lym) < 800/μL. Blood test values closest to day 14 out of 11–17 days of hospitalization were used. The primary outcome was a Barthel Index (BI) < 90, while secondary outcomes were the results of various PICS assessments, including mental and cognitive impairments, performed at the PICS clinic. We supplemented missing data with multiple imputations by chained equations. We performed a nominal logistic regression analysis with age, sex, BMI, SOFA, and the presence of PIICS as variables for BI < 90. Results: Forty-three out of two hundred seventy-three PICS outpatients met the diagnostic criteria for PIICS during hospitalization. In comparisons with non-PIICS patients, significantly higher severity scores for APACHE II and SOFA and a longer hospital stay were observed in PIICS patients, suggesting a higher clinical severity. The primary outcome, BI, was lower in the PIICS group (97.5 (58.5, 100) vs. 100 (95, 100), p = 0.008), as were the secondary outcomes (FSS-ICU: 35 (31, 35) vs. 35 (35, 35), MRC score: 55 (50.25, 58) vs. 58 (53, 60), grip strength: 16.45 (9.2, 25.47) vs. 20.4 (15.3, 27.7)). No significant differences were noted in mental or cognitive function assessments, such as HADS, IES-R, and SMQ. A multivariable analysis supplemented with missing data revealed that PIICS (odds ratio: 1.23 (1.08–1.40 p = 0.001) and age (odds ratio: 1.007 (1.004–1.01), p < 0.001) correlated with BI < 90, independent of clinical severity such as sequential organ failure assessment (SOFA). Similar results were obtained in the sensitivity analysis excluding missing data. Conclusions: The present study revealed a strong relationship between PIICS and post-discharge PICS physical dysfunction in patients requiring intensive care. Full article

Background: The identification of the branch of the inferior medial genicular artery (bIMGA) in anterior cruciate ligament reconstructions (ACLRs) has previously been considered a landmark by some surgeons, but its consistency remains debated. The aim of this investigation was to evaluate the variability in the appearance and location of bIMGA and to assess its validity as a reliable landmark during hamstring tendon harvesting procedures. Methods: This prospective, single-center study comprised 213 patients who underwent ACLR over a period of two years. The surgical procedures were conducted by the same surgical team, maintaining uniformity in the approach. The study sought correlations between patient demographics, level of activity, and the potential for successful identification of the bIMGA. Results: A statistically significant association between patient activity levels and successful identification of the bIMGA (p = 0.035) was observed. No significant correlations were found concerning patient demographic characteristics. bIMGA demonstrated a substantial degree of anatomical variability, rendering its consistent identification in the surgical field challenging. Conclusions: Given the observed variability and the associated difficulty in its identification, the use of the bIMGA as a dependable anatomical reference during ACL graft harvesting is not recommended. This study confirms the inconsistency of bIMGA as a traditional landmark, underscoring the need for research aimed at identifying more consistent and reliable anatomical references to enhance the precision of surgical interventions in ACLR. Full article

New imaging technologies play a pivotal role in the current management of patients with prostate cancer. Robotic assisted radical prostatectomy (RARP) is a standard of care for localized disease and through the already imaging-based console subject of research towards combinations of imaging technologies and RARP as well as their impact on surgical outcomes. Therefore, we aimed to provide a comprehensive analysis of the currently available literature for new imaging technologies for RARP. On 24 January 2023, we performed a systematic review of the current literature on Pubmed, Scopus and Web of Science according to the PRISMA guidelines and Oxford levels of evidence. A total of 46 studies were identified of which 19 studies focus on imaging of the primary tumor, 12 studies on the intraoperative tumor detection of lymph nodes and 15 studies on the training of surgeons. While the feasibility of combined approaches using new imaging technologies including MRI, PSMA-PET CT or intraoperatively applied radioactive and fluorescent dyes has been demonstrated, the prospective confirmation of improvements in surgical outcomes is currently ongoing. Full article

The red cell distribution width (RDW) is the coefficient of variation of the mean corpuscular volume (MCV). We sought to evaluate RDW as a predictor of outcomes following acute medical admission. We studied 10 years of acute medical admissions (2002–2011) with subsequent follow-up to 2021. RDW was converted to a categorical variable, Q1 < 12.9 fl, Q2–Q4 ≥ 12.9 and <15.7 fL and Q5 ≥ 15.7 fL. The predictive value of RDW for 30-day in-hospital and long-term mortality was evaluated with logistic and Cox regression modelling. Adjusted odds ratios (aORs) were calculated and loss of life years estimated. There were 62,184 admissions in 35,140 patients. The 30-day in-hospital mortality (n = 3646) occurred in 5.9% of admissions. An additional 15,086 (42.9%) deaths occurred by December 2021. Admission RDW independently predicted 30-day in-hospital mortality aOR 1.93 (95%CI 1.79, 2.07). Admission RDW independently predicted long-term mortality aOR 1.04 (95%CI 1.02, 1.05). Median survival post-admission was 189 months. For those with admission RDW in Q5, observed survival half-life was 133 months—this represents a shortfall of 5.7 life years (33.9%). In conclusion, admission RDW independently predicts 30-day in-hospital and long-term mortality. Full article

The Mild Behavioral Impairment (MBI) concept was developed to determine whether late-onset persistent neuropsychiatric symptoms (NPSs) may be early manifestations of cognitive decline. Our study aims to investigate the prevalence and differentiating features of MBI with respect to major neurocognitive disorders (MNDs) and primary psychiatric disorders (PPDs). A total of 144 elderly patients who were referred to our psychogeriatric outpatient service were recruited. The severity of mental illness was evaluated by means of the Clinical Global Impression Severity scale, the severity of psychopathology was evaluated by means of the Brief Psychiatric Rating Scale (BPRS), and overall functioning was evaluated by means of the Global Assessment of Functioning scale. The sample included 73 (50.6%) patients with PPDs, 40 (27.8%) patients with MBI, and 31 (21.5%) patients with MNDs. Patients with MNDs reported the greatest severity of mental illness, the highest BPRS Total, Psychosis, Activation, and Negative Symptom scores, and the lowest functioning. Patients with MBI and PPDs had comparable levels of severity of mental illness and overall functioning, but MBI patients reported higher BPRS Total and Negative Symptom scores than PPD patients. Patients with MBI frequently reported specific clinical features, including a higher severity of apathy and motor retardation. These features merit further investigation since they may help the differential diagnosis between MBI and PPDs. Full article

Urinary stress incontinence is a distressing condition that has a severe impact on quality of life for most affected women. The insertion of the suburethral tension-free vaginal tape (TVT) is regarded as the gold-standard surgical treatment option. It is unclear whether all women with severe SUI benefit equally from TVT. Thus, the aim of our study was to identify risk factors for severe SUI and determine whether successful the resolution of incontinence after a TVT procedure was different in women with a higher degree of SUI. In total, 168 women were included in this retrospective cohort study. Women with severe SUI showed a significantly lower maximum urethral closure pressure (MUCP) (median 53 cmH₂O in moderate vs. 39 cmH₂O in severe, p = 0.001) and higher BMI (median 26.1 kg/m² in moderate vs. 28.5 kg/m² in severe, p = 0.045). Sonographic bladder neck funneling was detected significantly more often in women with severe SUI (27% in moderate vs. 57% in severe, p = 0.004). Lower MUCP and higher BMI were identified as significant predictors of severe SUI (p < 0.032). There was no difference in parity, age, functional urethral length and negative urethral stress pressure. Overall postoperative continence after the insertion of TVT was 91.9%. We found no significant difference in postoperative continence between women with severe vs. moderate SUI, suggesting that in our cohort the success of TVT was not significantly affected by the severity of SUI. In our cohort, low MUCP and high BMI were shown to be significant predictors of SUI severity. Nevertheless, treatment success of SUI with TVT did not differ substantially in women with more severe SUI. Full article

Birth weight is a marker that is often referred to determine newborn health, potential growth trajectories and risk of future disease. Accordingly, interventions to promote appropriate and healthy birth weight have been extensively studied and implemented in pregnancy. In particular, physical activity in pregnancy is recommended to promote appropriate fetal development and newborn birth weight. This systematic review and meta-analyses aimed to summarize the effect of physical activity during pregnancy specifically from randomized controlled trials on the following outcomes: birth weight, macrosomia, low birth weight, being large for the gestational age, and being small for the gestational age (Registration No.: CRD42022370729). 63 studies (16,524 pregnant women) were included. There was a significant negative relationship between physical activity during pregnancy and macrosomia (z = 2.16; p = 0.03; RR = 0.79, 95% CI = 0.63, 0.98, I² = 29%, P_{heterogeneity} = 0.09). No other significant relationships were found. Promoting physical activity during pregnancy may be an opportune time to reduce the risk of future chronic disease, such as obesity, through the prevention of macrosomia and the promotion of appropriate birth weights. Full article

Knee range of motion and patient-reported outcome measures (PROMs) are often used as screening tools to assess the severity of knee osteoarthritis and guide the decision to refer patients to an arthroplasty clinic. However, there is little understanding regarding the correlation between these factors. Thus, the purpose of this study was to determine the correlation between patient-reported clinical function measured with the Oxford Knee Score (OKS), pain assessed using the visual analog scale (VAS), knee range of motion (ROM), and characteristic radiographic features in patients with advanced osteoarthritis of the knee. A prospective analysis of a consecutive series of 138 patients with advanced unilateral osteoarthritis (OA) of the knee was performed. The severity of radiographic OA was classified according to the most commonly used Kellgren and Lawrence classification (K&L). Spearman’s rank correlation analysis and multiple linear regression analysis were performed. The OKS was used as a dependent variable and was adjusted for pain, ROM, and nine standardized radiographic parameters on multiple views of the tibiofemoral and patellofemoral joint. OKS and pain correlated weakly with the K&L grade (r = −0.289; p = 0.001; r = 0.258; p = 0.002). K&L grade and the degree of patellofemoral joint space narrowing were identified as independent factors being associated with a poorer OKS (coefficient −4.528, p = 0.021; coefficient −2.211, p = 0.038). Slightly worse results were identified for OKS and pain in patients with K&L grade 4 osteoarthritis compared to patients with K&L grade 3 osteoarthritis (∆OKS 5.5 points, p < 0.001; ∆VAS 1.7 points, p = 0.003). There was no significant difference for passive range of motion between patients with K&L grade 3 or 4. When counseling patients with advanced knee osteoarthritis who may be eligible for knee arthroplasty, it is essential to give primary consideration to pain levels and self-reported limitations experienced during daily activities. Relying solely on knee ROM and PROMs is not an effective screening method for guiding the decision to refer patients to an arthroplasty clinic. Full article

(1) Background: The complexity of the perioperative outcome for patients with gastric cancer is not well reflected by single quality metrics. To study the effect of the surgical outcome on survival, we have evaluated the relationship between textbook outcome (TO)—a new composite parameter—and oncological outcome. (2) Methods: All patients undergoing total gastrectomy or trans-hiatal extended gastrectomy for gastric cancer with curative intent between 2017 and 2021 at our institution were included. TO was defined by negative resection margins (R0); collection of ≥25 lymph nodes; the absence of major perioperative complications (Clavien–Dindo ≥ 3); the absence of any reintervention; absence of unplanned ICU re-admission; length of hospital stay < 21 days; absence of 30-day readmission and 30-day mortality. We evaluated factors affecting TO by multivariate logistic regression. The correlation between TO and long-term survival was assessed using a multivariate cox proportional-hazards model. (3) Results: Of the patients included in this study, 52 (52.5 %) achieved all TO metrics. Open surgery (p = 0.010; OR 3.715, CI 1.334–10.351) and incomplete neoadjuvant chemotherapy (p = 0.020, OR 4.278, CI 1.176–15.553) were associated with failure to achieve TO on multivariate analysis. The achievement of TO significantly affected overall survival (p = 0.015). TO (p = 0.037, OD 0.448, CI 0.211–0.954) and CCI > 4 (p = 0.034, OR 2.844, CI 1.079–7.493) were significant factors affecting DFS upon univariate analysis. In multivariate analysis, CCI > 4 (p = 0.035, OR 2.605, CI 0.983–6.905) was significantly associated with DFS. (4) Conclusions: We identified patient- and procedure-related factors influencing TO. Importantly, achieving TO is strongly associated with improved long-term survival in gastric cancer patients and merits further focus on surgical quality improvement efforts. Full article

Purpose: The present systematic review aimed to investigate the accuracy of zygomatic implant (ZI) placement using dynamic computer-aided surgery (d-CAIS), static computer-aided surgery (s-CAIS), and a free-hand approach in patients with severe atrophic edentulous maxilla and/or deficient maxilla. Methods: Electronic and manual literature searches until May 2023 were performed in the PubMed/Medline, Scopus, Cochrane Library, and Web of Science databases. Clinical trials and cadaver studies were selected. The primary outcome was planned/placed deviation. Secondary outcomes were to evaluate the survival of ZI and surgical complications. Random-effects meta-analyses were conducted and meta-regression was utilized to compare fiducial registration amounts for d-CAIS and the different designs of s-CAIS. Results: A total of 14 studies with 511 ZIs were included (Nobel Biocare: 274, Southern Implant: 42, SIN Implant: 16, non-mentioned: 179). The pooled mean ZI deviations from the d-CAIS group were 1.81 mm (95% CI: 1.34–2.29) at the entry point and 2.95 mm (95% CI: 1.66–4.24) at the apex point, and angular deviations were 3.49 degrees (95% CI: 2.04–4.93). The pooled mean ZI deviations from the s-CAIS group were 1.19 mm (95% CI: 0.83–1.54) at the entry point and 1.80 mm (95% CI: 1.10–2.50) at the apex point, and angular deviations were 2.15 degrees (95% CI: 1.43–2.88). The pooled mean ZI deviations from the free-hand group were 2.04 mm (95% CI: 1.69–2.39) at the entry point and 3.23 mm (95% CI: 2.34–4.12) at the apex point, and angular deviations were 4.92 degrees (95% CI: 3.86–5.98). There was strong evidence of differences in the average entry, apex, and angular deviation between the navigation, surgical guide, and free-hand groups (p < 0.01). A significant inverse correlation was observed between the number of fiducial screws and the planned/placed deviation regarding entry, apex, and angular measurements. Conclusion: Using d-CAIS and modified s-CAIS for ZI surgery has shown clinically acceptable outcomes regarding average entry, apex, and angular deviations. The maximal deviation values were predominantly observed in the conventional s-CAIS. Surgeons should be mindful of potential deviations and complications regardless of the decision making in different guide approaches. Full article

Hemophilia is a chronic, congenital/hereditary and X-linked disease, characterized by an insufficiency of factors VIII or IX, which are necessary for blood clotting. Those affected by hemophilia often suffer from particular psychosocial problems, both in the acceptance, coping, treatment and self-management of their disease and in their family and social relationships, which are often mediated by these circumstances. The aim of this study was to explore the experiences of people with hemophilia or their family members, of in a specific region of Spain, regarding the impact of having hemophilia. Structured interviews were conducted and developed, using the studies of the World Federation of Hemophilia and Osorio-Guzmán et al. as a guide, as well as a literature review of qualitative work on hemophilia. Data were analyzed using a six-step thematic analysis. A total of 34 interviews were thematically analyzed. The results showed that three key themes emerged from the data: (1) the daily impact of having hemophilia, (2) uncertainty about the disease, (3) the role of associations and (4) support from institutions. The results make it clear that the disease has a major impact on their lives (work, family, leisure and personal environment). The main conclusion is that hemophilia has a negative impact on the daily lives of patients, families and caregivers. Full article

Introduction: Women with bladder endometriosis often present with more advanced stages of endometriosis. Robotic surgery has emerged as a promising approach to the management of bladder endometriosis. This systematic review aims to analyze the current literature on robotic surgery for bladder endometriosis and describe our systematic approach to surgical treatment. Methods: This review followed the PRISMA guidelines, which ensured a comprehensive and transparent approach to selecting and evaluating relevant studies. We conducted a thorough literature search to identify studies that investigated the use of robotic surgery for bladder endometriosis. Relevant databases were searched, and inclusion and exclusion criteria were applied to select eligible studies. Data extraction and analysis were performed to assess the outcomes and effectiveness of robotic surgery for the treatment of bladder endometriosis. Results: We did not find any randomized clinical trials with the use of robotics in the treatment of bladder endometriosis. We found only two retrospective studies comparing robotic surgery with laparoscopy, and another retrospective study comparing robotic surgery, laparoscopy, and laparotomy in the treatment of bladder endometriosis. All the other 12 studies were solely case reports. Despite the lack of robust evidence in the literature, the studies demonstrated that robotic surgery is feasible and is associated with reduced postoperative pain, shorter hospital stays, and faster recovery. Conclusions: The utilization of robotic technology is a promising option for the surgical management of bladder endometriosis. We advocate a surgical systematic approach for the robotic treatment of bladder endometriosis. Robotic technology, with its 3D vision, instrumental degrees of freedom, and precision, particularly in suturing, may provide potential benefits over traditional laparoscopy. Full article

The gray matter/white matter (GM/WM) boundary of the brain is vulnerable to shear strain associated with mild traumatic brain injury (mTBI). It is, however, unknown whether GM/WM microstructure is associated with long-term outcomes following mTBI. The diffusion and structural MRI data of 278 participants between 18 and 65 years of age with and without military background from the Department of Defense INTRuST study were analyzed. Fractional anisotropy (FA) was extracted at the GM/WM boundary across the brain and for each lobe. Additionally, two conventional analytic approaches were used: whole-brain deep WM FA (TBSS) and whole-brain cortical thickness (FreeSurfer). ANCOVAs were applied to assess differences between the mTBI cohort (n = 147) and the comparison cohort (n = 131). Associations between imaging features and post-concussive symptom severity, and functional and cognitive impairment were investigated using partial correlations while controlling for mental health comorbidities that are particularly common among military cohorts and were present in both the mTBI and comparison group. Findings revealed significantly lower whole-brain and lobe-specific GM/WM boundary FA (p < 0.011), and deep WM FA (p = 0.001) in the mTBI cohort. Whole-brain and lobe-specific GM/WM boundary FA was significantly negatively correlated with post-concussive symptoms (p < 0.039), functional (p < 0.016), and cognitive impairment (p < 0.049). Deep WM FA was associated with functional impairment (p = 0.002). Finally, no significant difference was observed in cortical thickness, nor between cortical thickness and outcome (p > 0.05). Findings from this study suggest that microstructural alterations at the GM/WM boundary may be sensitive markers of adverse long-term outcomes following mTBI. Full article

Coronary artery disease (CAD) is a common finding in patients suffering from aortic valve stenosis (AS), with a prevalence of over 50% in patients 70 years of age or older. Transcatheter aortic valve intervention (TAVI) is the standard treatment option for patients with severe AS and at least 75 years of age. Current guidelines recommend percutaneous coronary intervention (PCI) in patients planned for TAVI with stenoses of >70% in the proximal segments of non-left main coronary arteries and in >50% of left main stenoses. While the guidelines on myocardial revascularization clearly recommend functional assessment of coronary artery stenoses of less than 90% in the absence of non-invasive ischemia testing, a statement regarding invasive functional testing in AS patients with concomitant CAD is lacking in the recently published guideline on the management of valvular heart disease. This review aims to provide an overview of the hemodynamic background in AS patients, discusses and summarizes the current evidence of invasive functional testing in patients with severe AS, and gives a future perspective on the ongoing trials on that topic. Full article

Research in healthcare is increasingly focused on quality assurance and continuous quality improvement aiming to promote service quality. Satisfaction is a key endpoint in outcomes research and service benchmarking, along with “traditional” clinical outcomes. What controls stroke survivors’ satisfaction differs among qualitative studies’ conclusions, but there is general consensus on the importance of communication, improvement in activity, and engagement in goal setting. This review aims to collect and synthesise studies of the satisfaction of stroke survivors with rehabilitation services. A systematic search was conducted in seven electronic databases, including CINAHL, OVID, Pedro, Scopus Midline, Web of Science, and PubMed. The database search yielded 1339 studies, while one additional work was identified through hand searching. After removing duplicates, 74 studies were read in full, and after resultant exclusions, 12 qualitative studies were systematically reviewed, extracted, and appraised by two reviewers independently (HAS and RT) and the third reviewer (CS) was available for any disagreement. Five analytical themes were identified: Healthcare Professional–Patient Relationship (HCP), Delivery Service, Perceived Patient Autonomy (PPA), Expectations Shape Satisfaction, and Culture Influences Satisfaction. The studies of survivors’ satisfaction, experiences, and their rehabilitative needs with the services they receive have provided different factors that influence their satisfaction during rehabilitation in different countries worldwide. However, the context in which the studies were conducted is quite limited, and more detailed studies are required for many underexplored contexts. Full article

Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory spondyloarthropathy characterized by ectopic calcification of spinal cord tissue. Its etiology is possibly polygenic. However, its pathogenesis and systemic effects remain unclear. Recent studies have reported a high prevalence of DISH in heart failure patients. The authors investigated how the incidence and severity of DISH are associated with vascular calcification and the occurrence of cardiovascular events. In this retrospective chart review study, 500 patients with cardiovascular disease who underwent surgery (cardiovascular events group) and 500 patients with non-cardiovascular disease who underwent computed tomography scans (non-cardiovascular events group) were randomly selected to investigate the degree of ossification of the anterior longitudinal ligament and the incidence of DISH. We found that the incidence of DISH was higher in patients with cardiovascular events and that patients with DISH had more calcification of the coronary arteries and aorta. Next, we examined the relationship between the degree of coronary and aortic calcification, the incidence of DISH, and the degree of ossification of the anterior longitudinal ligament in the non-cardiovascular event group. The prevalence of DISH in the cardiovascular and non-cardiovascular groups was 31.4% and 16.5%, respectively (p = 0.007). Aortic calcification and a predominant degree of vascular calcification with a certain level of ossification of the anterior longitudinal ligament suggest some correlation between DISH and cardiovascular events. This study is important in understanding the pathophysiology and pathogenesis of DISH. Full article

Background/Aims: Although the World Health Organization declared the end of the public health emergency of international concern focusing on COVID-19 in May 2023, this bothersome virus continues to mutate, and the possibility of the emergence of mutant strains with high infectivity and severe disease rates has not disappeared. Thus, medical evidence must be accumulated, which is indispensable for protecting both patients under immunosuppressive treatments and the healthy population. This study examined SARS-CoV-2 vaccination responses in Japanese patients with autoimmune hepatitis (AIH) compared with healthy controls. Methods: This observational study registered 22 patients with histologically diagnosed AIH and 809 healthy controls in our hospital. Their Elecsys anti-SARS-CoV-2 spike antibody concentrations before and after vaccination were evaluated. Results: In this study, 72.7% and 18.2% of patients with AIH received steroids and azathioprine, respectively. Significant negative correlations were found between age and anti-SARS-CoV-2 spike antibody concentration in both groups; however, no sex differences were found. Although anti-SARS-CoV-2 spike antibody concentration was drastically augmented after the second vaccination (p < 0.05) in the AIH group, these levels were significantly lower than those in the controls (p < 0.05). In the age- and sex-matched analysis, the population ratio with a minimum response (≤100 binding antibody units (BAU/mL) was higher among patients with AIH than among controls 26 weeks after the second vaccination (44% vs. 7%, p < 0.05). Conclusions: The anti-SARS-CoV-2 spike antibody concentration in AIH patients was significantly lower than that in controls after the second vaccination. Continued and widespread vaccination, particularly for patients requiring medical immunomodulation, is recommended. Full article

Background: Meta-analyses (MAs) and network meta-analyses (NMAs) are high-quality studies for assessing drug efficacy, but they are time-consuming and may be affected by biases. The capacity of artificial intelligence to aggregate huge amounts of information is emerging as particularly interesting for processing the volume of information needed to generate MAs. In this study, we analyzed whether the chatbot ChatGPT is able to summarize information in a useful fashion for providers and patients in a way that matches up with the results of MAs/NMAs. Methods: We included 16 studies (13 NMAs and 3 MAs) that evaluate biologics (n = 6) and both biologic and systemic treatment (n = 10) for moderate-to-severe psoriasis, published between January 2021 and May 2023. Results: The conclusions of the MAs/NMAs were compared to ChatGPT’s answers to queries about the molecules evaluated in the selected MAs/NMAs. The reproducibility between the results of ChatGPT and the MAs/NMAs was random regarding drug safety. Regarding efficacy, ChatGPT reached the same conclusion as 5 out of the 16 studies (four out of four studies when three molecules were compared), gave acceptable answers in 7 out of 16 studies, and was inconclusive in 4 out of 16 studies. Conclusions: ChatGPT can generate conclusions that are similar to MAs when the efficacy of fewer drugs is compared but is still unable to summarize information in a way that matches up to the results of MAs/NMAs when more than three molecules are compared. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting up to 20% of children. Methotrexate (MTX) is used off-label as a systemic treatment for AD patients unresponsive to topical therapies, but limited data exist regarding its safety and efficacy in children, especially in those < 4 years old. To further investigate MTX in younger patients, we screened the medical records of three referral centers between 2016 and 2022 and identified 28 infants and toddlers < 4 years old with AD treated with MTX. Mean age upon MTX initiation was 2.7 ± 1.2 years and mean investigator global assessment (IGA) score was 3.78 ± 0.4. Median duration of MTX treatment was five months. Following 12 and 24 weeks of MTX treatment, the response rate was 50% and IGA 0/1 was achieved in 14.2% and 21.4% of patients, respectively. Most treatment cessations were attributed to a lack of efficacy or parental concern. Although adverse events were reported in 57.1% of patients, MTX was discontinued due to such adverse events only in two patients (7.1%). Taken together, MTX demonstrated a high safety profile in AD patients <4 years old. MTX efficacy was moderate and presumably underestimated by parents who opted for premature treatment cessation due to concerns associated with an immunomodulatory drug. Full article

Level of Evidence: Level 2. Purpose: To compare the safety and efficacy of vascular plug (VP) and vascular plug and polidocanol foam (VPPF) treatments for embolization in pelvic congestion syndrome (PCS). Materials and methods: A comparative, prospective, two-center study enrolled 50 women with PCS from January 2019 to January 2020. The patients were divided into two groups, and embolization was performed with VP (n = 25) and VPPF (n = 25) treatments. The mean age of the patients was 45.6 years ± 6.9. Three clinical parameters were assessed: abdominal pain, dyspareunia, and lower limb pain. The primary outcome (clinical success at 1 yr using a VAS), number of devices, procedure and fluoroscopy times, radiation doses, costs, and complications were compared. The participants were followed-up at 1, 3, 6, and 12 months. Results: At the 1-year follow-up, clinical success did not significantly differ between the two groups (VP vs. VPPF) regarding the improvement of the symptoms analyzed (pelvic pain, dyspareunia, lower extremity pain, and other symptoms (p < 0.05)). The mean number of devices per case was 4 ± 1.1 for the VP group and 2 ± 0.31 for the VPPF group (p < 0.001). No major complications were recorded in either group. The VPPF group had a significantly longer fluoroscopy time (42.8 min ± 14.2 vs. 25.4 min ± 7) and longer radiation dose (VPPF air kerma 839.4 ± 513 vs. VP air kerma 658.4 mGy ± 355 (all p < 0.001)). Conclusions: Embolization for PCS resulted in pain relief in 90% of patients; the use of polidocanol did not demonstrate changes in the clinical outcome. The use of a VP alone was associated with decreased fluoroscopy time and radiation dose. Full article

Background: The aim of this study was to assess the prevalence, characteristics, and determinants of apparent treatment-resistant hypertension (aTRH) in an unselected large population of patients with end-stage kidney disease (ESKD) treated with hemodialysis (HD) throughout the country. Methods: A database of 5879 patients (mean age 65.2 ± 14.2 years, 60% of males receiving hemodialysis) was obtained from the biggest provider of hemodialysis in the country. Hypertension and aTRH were defined using pre- or/and post-dialysis BP values. Patients with and without aTRH (non-aTRH) were compared. Results: Using pre- and post-dialysis criteria, hypertension was diagnosed in 90.7% and 89.1% of subjects, respectively. According to pre- and post-dialysis blood pressure criteria, aTRH incidences were 40.9% and 38.4%, respectively. The hypertensive patients with aTRH versus non-aTRH were younger, had a higher rate of cardiovascular disease, lower dialysis vintage, shorter time on dialysis, higher eKt/V, higher ultrafiltration, higher pre- and post-dialysis BP and HR, and higher use of antihypertensive drugs. Factors that increase the risk of aTRH according to both pre- and post-dialysis BP criteria were age—OR 0.99 [0.98–0.99] and 0.99 [0.98–0.99], the history of CVD 1.26 [1.08–1.46] and 1.30 [1.12–1.51], and diabetes 1.26 [1.08–1.47] and 1.28 [1.09–1.49], adjusted OR with 95% CI. Conclusions: In the real-life world, as much as 40% of HD patients may have aTRH. In ESKD HD patients, aTRH seems to be multifactorial, influenced by patient-related rather than dialysis-related factors. Various definitions of aTRH preclude easy comparisons between studies. Full article

Background: Chronic skin diseases have been recognised as having a detrimental effect on patients’ social functions. Objectives: To assess the perceived social support in patients with chronic skin disease and its associated factors. Methods: A cross-sectional study was conducted between January and April 2019 on patients with skin diseases taking treatment at Asir Central Hospital, Abha, Saudi Arabia. Patients of both sexes aged above 18 years undergoing treatment for a skin disease in ACH for more than 3 months (chronic skin disease) were recruited by simple random sampling, and a total of 249 patients returned completed questionnaires. A self-administered questionnaire was used to collect relevant information about the background and disease characteristics of the patients and the Multidimensional Scale of Perceived Social Support (MSPSS). The software package IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY, USA: IBM Corp., was used for data entry and analysis. Descriptive statistics were used for patient characteristics, and perceived social support was analysed according to specific scoring criteria. The Kruskal–Wallis test and Mann–Whitney U test were used to find out the association of background and disease variables with the perceived social support. Correlation analysis was used to find the relationship of social support with the age of the patient. All associations were considered significant at p < 0.05. Result: The mean age of the study group was 36.52 ± 14.22 years. The majority of the patients were females (71.1%). Atopic dermatitis was the most common skin disease reported, with 22.1% of all patients suffering from it. Mean scores of perceived social support score were low globally (24.97 ± 12.31), as well as in the three dimensions of significant other (7.75 ± 4.14), friends (7.90 ± 4.59), and family support (9.40 ± 5.48). A significant difference in social support was perceived by patients with a disease duration of 3 months to 1 year and those with papulo-squamous skin disease as compared to acne. The presence of skin disease in a second-degree relative indicated a higher level of social support perception and had a significant positive correlation (r = 0.194, p = 0.002) with the age of the patient. Conclusion: Saudi patients with chronic skin disease have low social support. Some important insights into the functioning of social support were suggested by the study finding, which pointed to the significant effect of disease duration, type of disease, and presence of disease in second-degree relatives on the perception of social support in patients with a variety of chronic skin diseases. Qualitative exploratory and prospective research could help in understanding this aspect of psychosocial health in a better way and help to provide solutions. Full article

Cholesterol efflux capacity (CEC), the ability of high-density lipoprotein (HDL) cholesterol to accept cholesterol from macrophages, has been linked to cardiovascular events. Systemic lupus erythematosus (SLE) is characterized by the consumption of complement (C) proteins and has been associated with an increased risk of cardiovascular disease. CEC is reduced in SLE patients compared to controls. In the present work, our objective was to analyze whether the disruption of C influences CEC in patients with SLE. New-generation functional assays of the three pathways of the C system were performed in 207 patients with SLE. Additionally, serum levels of inactive (C1q, C2, C3, C4, and factor D) and activated (C3a) molecules, and regulators (C1-inhibitor and factor H) of C system were measured. CEC, using an in vitro assay, and lipoprotein serum concentrations were assessed. Multivariable linear regression analysis was performed to assess the relationship between C system and CEC. After full multivariable analysis, the alternative C cascade functional test showed a significant and negative relationship with CEC. This was also the case for C2 and C3, in which the associations were found to be positive and statistically significant, after adjustment for covariates. In conclusion, C system and CEC are interconnected in patients with SLE. Full article

The clinical manifestations of asthma in children are highly variable, are associated with different molecular and cellular mechanisms, and are characterized by common symptoms that may diversify in frequency and intensity throughout life. It is a disease that generally begins in the first five years of life, and it is essential to promptly identify patients at high risk of developing asthma by using different prediction models. The aim of this review regarding the early prediction of asthma is to summarize predictive factors for the course of asthma, including lung function, allergic comorbidity, and relevant data from the patient’s medical history, among other factors. This review also highlights the epigenetic factors that are involved, such as DNA methylation and asthma risk, microRNA expression, and histone modification. The different tools that have been developed in recent years for use in asthma prediction, including machine learning approaches, are presented and compared. In this review, emphasis is placed on molecular mechanisms and biomarkers that can be used as predictors of asthma in children. Full article