J. Pers. Med., Volume 14, Issue 10 (October 2024) – 52 articles

Background: Few studies have compared the efficacy and safety of second-line biological therapies in ulcerative colitis (UC) patients with prior exposure to anti-tumor necrosis factor (TNF) therapy. We aim to compare the efficacy and safety between ustekinumab, vedolizumab, and tofacitinib, a current option as second-line biological therapy with different mechanisms in those patients. Methods: This retrospective multi-center study was conducted across five institutions from 2011 to 2022. We enrolled patients with moderate to severe UC who failed anti-TNF therapy and subsequently received ustekinumab, vedolizumab, or tofacitinib as second-line biological therapy. The outcomes were analyzed for clinical response/remission and endoscopic improvement/remission rates after induction therapy, drug persistency, and adverse events. Results: A total of 70 UC patients were included and grouped into ustekinumab (11 patients), vedolizumab (40 patients), and tofacitinib (19 patients) treatments. The clinical response/remission rates after induction therapy were similar between ustekinumab (90.9/81.8%), vedolizumab (92.5/65.0%), and tofacitinib (94.7/73.7%). There were no significant differences in the endoscopic improvement/remission rates between the three groups: 90.9/18.2% for ustekinumab, 72.5/12.5% for vedolizumab, and 84.2/26.3% for tofacitinib. Drug persistence was similar across the three agents (p = 0.130). Three patients of the tofacitinib group experienced adverse events (herpes zoster and hypertriglyceridemia). Conclusions: Based on real-world data, second-line biological therapy with ustekinumab, vedolizumab, and tofacitinib showed comparable efficacy in patients with moderate to severe UC with prior exposure to anti-TNF therapy. Full article

Background/Objectives: Elexacaftor, tezacaftor, and ivacaftor (ETI) have significantly improved lung function in people with cystic fibrosis (pwCF). Despite exceptional improvements in most cases, treatment-related inter-subject variability and drug–drug interactions that complicate modulator therapy have been reported. Methods: This retrospective analysis presents data on the serum concentration of ETI in our pwCF with full or reduced dosage from August 2021 to December 2023 via routine therapeutic drug monitoring (TDM). The data were compared with the maximum drug concentrations (Cmax) from the pharmaceutical company’s summary of product characteristics. Results: A total of 786 blood samples from 155 pwCF (41% female, 59% male) were analyzed. The examinations were divided into four groups: full dose within the given tmax (38.5% of all measurements), full dose outside the tmax (29%), reduced dose within the tmax (19.2%), and reduced dose outside the tmax (13.2%). In pwCF receiving the full dose and blood taken within the tmax, 45.3% of serum concentrations of elexacaftor, 51.1% of serum concentrations of ivacaftor, and 8.9% of serum concentrations of tezacaftor were found to be above the Cmax, respectively. For those on reduced doses within the tmax, 24.5% had a serum concentration of elexacaftor, 23.2% had a serum concentration of ivacaftor, and 2.5% had a serum concentration of tezacaftor above the Cmax, respectively. Conclusions: Many pwCF under ETI therapy have Cmax values for elexacaftor and ivacaftor above the recommended range, even on reduced doses or before the tmax was reached. This highlights the value of a TDM program. Further pharmacokinetic studies are necessary. Full article

A dominant event determining the course of heart failure (HF) includes the disruption of the delicate sodium (Na⁺) and water balance leading to (Na⁺) and water retention and edema formation. Although incomplete decongestion adversely affects outcomes, it is unknown whether interventions directly targeting (Na⁺), such as strict dietary (Na⁺) restriction, intravenous hypertonic saline, and diuretics, reverse this effect. As a result, it is imperative to implement (Na⁺)-targeting interventions in selected HF patients with established congestion on top of quadruple therapy with angiotensin receptor neprilysin inhibitor, β-adrenergic receptor blocker, mineralocorticoid receptor antagonist, and sodium glucose cotransporter 2 inhibitor, which dramatically improves outcomes. The limited effectiveness of (Na⁺)-targeting treatments may be partly due to the fact that the current metrics of HF severity have a limited capacity of foreseeing and averting episodes of congestion and guiding (Na⁺)-targeting treatments, which often leads to dysnatremias, adversely affecting outcomes. Recent evidence suggests that spot urinary sodium measurements may be used as a guide to monitor (Na⁺)-targeting interventions both in chronic and acute HF. Further, the classical (2)-compartment model of (Na⁺) storage has been displaced by the (3)-compartment model emphasizing the non-osmotic accumulation of (Na⁺), chiefly in the skin. 23(Na⁺) magnetic resonance imaging (MRI) enables the accurate and reliable quantification of tissue (Na⁺). Another promising approach enabling tissue (Na⁺) monitoring is based on wearable devices employing ion-selective electrodes for electrolyte detection, including (Na⁺) and (Cl^–). Undoubtably, further studies using 23(Na⁺)-MRI technology and wearable sensors are required to learn more about the clinical significance of tissue (Na⁺) storage and (Na⁺)-related mechanisms of morbidity and mortality in HF. Full article

Background: Glaucoma is a leading cause of irreversible blindness worldwide, necessitating precise management strategies tailored to individual patient characteristics. Artificial intelligence (AI) holds promise in revolutionizing the approach to glaucoma care by providing personalized interventions. Aim: This review explores the current landscape of AI applications in the personalized management of glaucoma patients, highlighting advancements, challenges, and future directions. Methods: A systematic search of electronic databases, including PubMed, Scopus, and Web of Science, was conducted to identify relevant studies published up to 2024. Studies exploring the use of AI techniques in personalized management strategies for glaucoma patients were included. Results: The review identified diverse AI applications in glaucoma management, ranging from early detection and diagnosis to treatment optimization and prognosis prediction. Machine learning algorithms, particularly deep learning models, demonstrated high accuracy in diagnosing glaucoma from various imaging modalities such as optical coherence tomography (OCT) and visual field tests. AI-driven risk stratification tools facilitated personalized treatment decisions by integrating patient-specific data with predictive analytics, enhancing therapeutic outcomes while minimizing adverse effects. Moreover, AI-based teleophthalmology platforms enabled remote monitoring and timely intervention, improving patient access to specialized care. Conclusions: Integrating AI technologies in the personalized management of glaucoma patients holds immense potential for optimizing clinical decision-making, enhancing treatment efficacy, and mitigating disease progression. However, challenges such as data heterogeneity, model interpretability, and regulatory concerns warrant further investigation. Future research should focus on refining AI algorithms, validating their clinical utility through large-scale prospective studies, and ensuring seamless integration into routine clinical practice to realize the full benefits of personalized glaucoma care. Full article

Background: The use of microvascular grafts is the gold standard in oral and maxillofacial surgery for the reconstruction of soft tissue and bony and combined defects. Graft loss is one of the most serious complications in the field of reconstructive surgery. A comprehensive analysis of factors influencing this is, therefore, essential. Methods: This hypothesis-generating study analyzed 251 patient cases of oral and maxillofacial surgery at the University Hospital Düsseldorf from 2016 to 2020 regarding patient- and therapy-specific parameters for their impact on graft survival. Results: Statistically significant influencing factors were found among the 80 parameters examined: treatment with antiplatelet medication and a BMI ≥ 24.5 at the time of surgery had a positive influence on graft survival, while existing diabetes mellitus, atrial fibrillation, tracheostomy, and a longer operation time had a statistically relevant negative influence. Conclusions: This work demonstrates the relevance of patient-specific risk stratification and the need for further research to develop a valid risk profile. Identifying high-risk patients with medium-sized defects, where alternatives to microvascular reconstruction are available, appears to be crucial for the clinical outcome. Full article

Background/Objectives: Preeclampsia (PE) is a systemic disease that affects 4.6% of pregnancies. Despite the existence of a first-trimester screening for the prediction of preterm PE, no consensus exists regarding neither the right moment to end the pregnancy nor the appropriate variables to estimate the prognosis. The objective of this study was to obtain a prediction model for perinatal death in patients with preterm PE, useful for clinical practice. Methods: Singleton pregnant women with PE and preterm delivery were included in an observational retrospective study. Multiple maternal and fetal variables were collected, and several multivariable logistic regression analyses were applied to construct models to predict perinatal death, selecting the most accurate and reproducible according to the highest area under the curve (AUC) and the lowest Akaike Information Criteria (AIC). Results: A group of 148 pregnant women were included, and 18 perinatal deaths were registered. Univariable logistic regression selected as statistically significant variables the following: gestational age (GA) at admission, fetal sex, poor response to antihypertensive drugs, PlGF, umbilical artery (UA) pulsatility index (PI), cerebroplacental ratio (CPR), and absent/reversed ductus venosus (DV). The multivariable model, including all these parameters, presented an AUC of 0.95 and an AIC of 76.5. However, a model including only GA and fetal sex presented a similar accuracy with the highest simplicity (AUC 0.93, AIC 67.6). Finally, in fetuses with a similar GA, fetal death became dependent on PlGF and fetal sex, underlying the role of fetal sex in all circumstances. Conclusions: Female fetal sex and low PlGF are notorious predictors of perinatal death in preterm PE, only surpassed by early GA at birth. Full article

Background: Prostate cancer is the fourth most common cancer and eighth leading cause of cancer-related mortality worldwide. Its incidence is increasing in South Korea. This study aimed to investigate a predictive model for the 5-year survival probability of prostate cancer patients in a Korean primary care setting. Method: This retrospective study used data from the nationwide insurance claims database. The main outcome was survival probability 5 years after the initial diagnosis of prostate cancer. Potential confounding factors such as age, body mass index (BMI), blood pressure, laboratory results, lifestyle behaviors, household income, and comorbidity index were considered. These variables were available in the national health check-up information. A Cox proportional hazards regression model was used to develop the predictive model. The predictive performance was calculated based on the mean area under the receiver operating characteristic curve (AUC) after 10-fold cross-validation. Results: The mean 5-year survival probability was 82.0%. Age, fasting glucose and gamma-glutamyl transferase levels, current smoking, and multiple comorbidities were positively associated with mortality, whereas BMI, alkaline phosphatase levels, total cholesterol levels, alcohol intake, physical activity, and household income were inversely associated with mortality. The mean AUC after 10-fold cross-validation was 0.71. Conclusions: The 5-year survival probability model showed a moderately good predictive performance. This may be useful in predicting the survival probability of prostate cancer patients in primary care settings. When interpreting these results, potential limitations, such as selection or healthy user biases, should be considered. Full article

Background/Objectives: In cases of myocarditis, electrocardiograms (ECGs) may suggest a pattern of ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI). NSTEMI patterns are less frequent in myocarditis cases, but it remains unclear if the presence of ST-segment elevation in myocarditis cases is related to a more severe condition and more damage in the myocardium. Methods: This is a retrospective study involving 38 patients admitted to hospital with myocarditis. Patients were divided into two groups: patients with ST-segment elevation (STE) patterns in the ECG (25), and patients without ST-segment elevation (non-STE) patterns (13). The data compared included results from epidemiological, laboratory, and instrumental tests. Data were analysed using IBM SPSS Statistics v26.0. A p value of <0.05 was established as the threshold for statistical significance. Results: C-reactive protein (CRP) levels were higher in the STE group (103.40 ± 82.04 mg/L vs. 43.54 ± 61.93 mg/L, p = 0.017). The left ventricle ejection fraction (LVEF) was significantly higher in the non-STE pattern group (49.71 ± 4.14 vs. 56.58 ± 3.99, p < 0.001). A lower LVEF correlates with higher TnI levels (r= −0.353, p = 0.032) and higher CRP levels (r = −0.554, p < 0.001). Lower left ventricle (LV) strain correlates with higher levels of Troponin I (TnI) (r = −0.641, p = 0.013). Conclusions: LVEFs in the STE group were lower compared to those in the non-STE pattern group. STE pattern was associated with higher CRP levels. Higher TnI levels in cases of myocarditis were associated with lower LV strain and lower LVEF; higher CRP levels also correlated with lower LVEF. Based on a 6-month echocardiographic follow-up, the prognosis of myocarditis was favourable. Full article

Background: Glycyrrhiza glabrata (licorice) is used in traditional medicine and herbal remedies and reduces sore throats consequent to intubation, but whether it is protective for more intense pain after oropharyngeal surgery remains unclear. We thus tested the joint hypothesis that gargling with licorice, which has anti-inflammatory and antioxidant properties, reduces postoperative pain and morphine consumption. Methods: We enrolled patients having elective oropharyngeal surgery. Participants were randomly allocated to gargle with either 1 g licorice or a sugar placebo before and for up to three days after surgery. A numerical rating scale (NRS) for pain along with morphine consumption was evaluated every 30 min during the post-anesthesia care unit (PACU) stay and then three times daily for three days. We pre-specified that licorice gargling would be deemed better than sugar gargling only if found non-inferior on both morphine consumption and pain score and superior on at least one of the two. Results: 65 patients were randomized to the licorice group and 61 to placebo. We found noninferiority (NI) in pain scores with an estimated mean difference of −0.09 (95.2% CI: −0.88, 0.70; p = 0.001; NI delta = 1) between licorice and placebo gargling. There were no adverse events reported in either group that required treatment discontinuation. Conclusions: Gargling with licorice did not significantly or meaningfully reduce postoperative pain or morphine consumption in patients recovering from oropharyngeal surgery. While higher doses might prove more effective, our results suggest that other topical analgesics should be considered. Full article

Aim: To assess the incidence and the temporal trend of type 1 diabetes (T1D) and diabetic ketoacidosis (DKA) during the period 2014–2023 in youths aged 0–14 years in the Trentino–Alto Adige region, Italy. Methods: A retrospective review of all incident cases of T1D diagnosed at the two Pediatric Diabetes Centers of Bolzano and Trento was matched with diabetes exemptions (No. 344). Demographic, clinical, and socioeconomic status (SES) data at first hospitalization were collected from subjects who agreed to participate (No. 272). Results: The incidence of T1D was 21.5/100,000 person/years, with a peak of 31.1 in 2021 during the COVID-19 pandemic. The mean age at the onset was 8.8 ± 3.9 years. Seventy-nine percent of the subjects were Italians, primarily residents in rural areas, and SES was equally represented. The mean incidence of DKA was 36.9%. The logistic regression analysis showed that the independent characteristics of the patients with DKA were of a younger age and displayed higher glycated hemoglobin (HbA1c) values. No relation of DKA with seasonality, ethnicity, or first-degree relative (FDR) with T1D or SES was detected. Conclusions: Our study revealed an incidence of T1D in the Trentino–Alto Adige region comparable to other areas in the North of Italy. The DKA rate negatively correlated with age; therefore, targeted prevention educational campaigns to increase awareness are needed. Full article

Diabetic kidney disease (DKD) is a prevalent microvascular complication of diabetes mellitus and is associated with a significantly worse prognosis compared to diabetic patients without kidney involvement, other microvascular complications, or non-diabetic chronic kidney disease, due to its higher risk of cardiovascular events, faster progression to end-stage kidney disease, and increased mortality. In clinical practice, diagnosis is based on estimated glomerular filtration rate (eGFR) and albuminuria. However, given the limitations of these diagnostic markers, novel biomarkers must be identified. Omics is a new field of study involving the comprehensive analysis of various types of biological data at the molecular level. In different fields, they have shown promising results in (early) detection of diseases, personalized medicine, therapeutic monitoring, and understanding pathogenesis. DKD is primarily utilized in scientific research and has not yet been implemented in routine clinical practice. The aim of this review is to provide an overview of currently available data on targeted omics. After an extensive literature search, 25 different (panels of) omics were withheld and analyzed. Both serum/plasma and urine proteomics and metabolomics have been described with varying degrees of evidence. For all omics, there is still a relative paucity of data from large, prospective, longitudinal cohorts, presumably because of the heterogeneity of DKD and the lack of patient selection in studies, the complexity of omics technologies, and various practical and ethical considerations (e.g., limited accessibility, cost, and privacy concerns). Full article

Introduction: This article juxtaposes case series with a systematic review to evaluate the feasibility, safety, and clinical outcomes of concurrent robotic multisite urological surgeries, specifically robot-assisted radical prostatectomy (RARP) and robot-assisted partial nephrectomy (RAPN), for synchronous prostate and kidney cancers. Aim: The aims of this study were to evaluate the feasibility, safety, and clinical outcomes of urological concurrent robotic multisite surgeries through a comparison of institutional findings with the existing literature. Materials and Methods: A retrospective analysis was conducted on eight institutional cases of concurrent robotic multisite surgeries performed between 2021 and 2024. The primary outcomes measured were operative time, blood loss, and postoperative complications. A systematic review of the literature was performed, searching PubMed, Embase, and Cochrane Library databases, with the last search conducted on 1 July 2024. Studies were included if they reported on concurrent robotic surgeries corresponding to the procedures performed at the institution, including RARP with RAPN, RARP with robotic transabdominal preperitoneal inguinal hernia repair (RTAPPIHR), and other multisite robotic surgeries. Risk of bias was assessed using the modified Newcastle–Ottawa Scale. Descriptive statistics were used to analyze operative time and blood loss, with confidence intervals (CIs) calculated to assess precision. Categorical variables, including postoperative complications, were summarized using frequencies and percentages. Heterogeneity was assessed using the I² statistic, with values above 50% indicating substantial heterogeneity. A random effects model was applied when necessary, and sensitivity analyses excluded studies with high risk of bias. Results: We describe a unique docking technique employed in our procedures, which allows for atraumatic transitions between surgeries using the same port sites. Our institutional cases demonstrated the feasibility and safety of concurrent robotic multisite surgery, with a mean operative time of 315 min (95% CI: 290–340) and mean blood loss of 300 mL (95% CI: 250–350). There were no significant intraoperative complications reported. These findings are consistent with the literature, where mean operative times range from 390 to 430 min and blood loss ranges from 200 to 330 mL. Notably, no positive surgical margins or declines in postoperative renal function were observed in our cases. The systematic review included nine retrospective studies involving 40 cases of concurrent RARP and RAPN, as well as eleven studies including 392 cases of RARP combined with RTAPPIHR. The findings from these studies support the feasibility and safety of concurrent surgeries, showing similar rates of operative time, blood loss, and postoperative complications. Conclusions: Concurrent robotic multisite surgeries, such as RARP combined with RAPN or RTAPPIHR, appear to be safe and feasible. Our data suggest these procedures are non-inferior to separate surgeries in terms of safety and complication rates. Potential benefits, including reduced operative times, shorter hospital stays, and more efficient resource use, may translate into cost savings, although no formal cost-effectiveness analysis was conducted. Limitations include the small sample size, retrospective design, and lack of long-term follow-up. Prospective trials are needed to validate these findings and further refine the techniques. Funding: this review did not receive any external funding. Registration: this review was not registered in any public protocol registry due to its comparative retrospective nature. Full article

Background: Most patients with ovarian cancer relapse within 2 years. Prospective randomized trials, such as DESKTOP III and SOC-I, have shown the role of secondary cytoreduction in improving oncological outcomes in selected patients, when complete tumor resection is achieved. Recent retrospective series suggest that minimally invasive surgery is a feasible option in oligometastatic recurrences, such as rectal ones. Methods: Five patients with an isolated rectal recurrence infiltrating the bowel wall underwent a robotic rectosigmoid resection with totally intracorporeal colorectal anastomosis. The procedure began with retroperitoneal access to manage the vascular structures, followed by visceral resection with a minimally invasive approach. The standard steps of an en-bloc pelvic resection, including intracorporeal end-to-end anastomosis, were performed. The treatment data were evaluated. Results: The mean age of the patients was 54 years, and their mean body mass index was 30. All patients had at least one previous abdominal surgery and 60% had high-grade serous ovarian cancer at their initial diagnosis. Their mean platinum-free interval was 17.4 months. Complete secondary cytoreduction was achieved in all cases, with histopathology confirming bowel infiltration. The mean procedure duration was 294 min, with an estimated blood loss of 180 mL. No intraoperative complications occurred. The mean hospital stay was 8 days. One patient had a grade 2 postoperative complication. The mean follow-up period was 14 months, with only one patient experiencing a recurrence at the level of the abdominal wall. Conclusions: Robotic rectosigmoid resection is a viable option for complete cytoreduction in isolated recurrent ovarian cancer. Full article

Corneal ectasias, including keratoconus (KC), pellucid marginal degeneration (PMD), and post-LASIK ectasia, poses significant visual rehabilitation challenges due to the resultant irregular astigmatism, myopia, and higher-order aberrations (HOAs). These conditions often resist traditional corrective methods, necessitating advanced optical solutions. Scleral lenses (SLs) have emerged as a primary non-surgical option for managing these complex corneal irregularities. SLs form a smooth optical interface by forming a tear-filled chamber between the lens and the cornea, effectively mitigating HOAs and improving both high-contrast and low-contrast visual acuity (VA). This review evaluates the efficacy of SLs in enhancing VA and reducing aberrations in patients with corneal ectasia. It also explores the technological advancements in SLs, such as profilometry and wavefront-guided systems, which enable more precise and customized lens fittings by accurately mapping the eye’s surface and addressing specific visual aberrations. The current body of evidence demonstrates that custom SLs significantly improve visual outcomes across various ectatic conditions, offering superior performance compared to conventional correction methods. However, challenges such as the complexity of fitting and the need for precise alignment remain. Ongoing innovations in SL technology and customization are likely to further enhance their clinical utility, solidifying their role as an indispensable tool in the management of corneal ectasias. Full article

Background: Obstetric brachial plexus injuries (OBPIs) not only lead to severe and life changing sequelae regarding motor impairment but can also be responsible for multi-characteristic pain. In everyday routine, questions regarding pain of the developing child with an OBPI are often overseen and neglected. We aimed to elucidate this specific question and analyzed all patients with OBPI treated in our center to unmask initially non-observed pain and ultimately put pain in correlation to the surgical reconstructive treatment performed. Methods: This single center retrospective study analyzes patients with OBPI treated in our center over the past 20 years. Patients were surveyed by the adolescent pediatric pain tool assessment to evaluate pain over their entire life span by excluding potential postoperative pain episodes. Results: A total of 95 patients were initially contacted of which 78 returned the questionnaire (53.8% female, 46.2% male). In our patient cohort, the vast majority constituting 84.6 percent did not experience pain in the affected upper extremity over the years up to the date of their examination. Most of the patients describing pain had not been microsurgically treated for brachial plexus reconstruction in their neonate period. Merely, 33.3 percent of all OBPI experiencing pain had been microsurgically reconstructed at a median age of 7 months. Conclusions: Pain interrogation in patients with OBPI is often overseen during daily clinical routine. Adequate age-appropriate analgesic therapy regimens adapted to the individual are highly recommended. Timely microsurgical brachial plexus reconstruction may result in reduced lifetime pain experiences. Full article

Background: Gamma Knife Radiosurgery (GKRS), a specific type of Stereotactic Radiosurgery (SRS), has developed as a significant modality in the treatment of glioblastoma, particularly in conjunction with standard chemotherapy. The goal of this study is to evaluate the efficacy of combining GKRS with surgical resection and chemotherapy in enhancing therapeutic effects for glioblastoma patients aged 55 years and older. Methods: This prospective clinical study, conducted in accordance with the STROBE guidelines, involved 49 glioblastoma patients aged 55 years and older, treated between January 2013 and January 2023. Data were collected prospectively, and strict adherence to the STUPP protocol was maintained. Only patients who conformed to the STUPP protocol were included in the analysis. Due to concerns regarding the cognitive impairment associated with conventional radiotherapy, and at the patients’ request, a radiosurgery plan was offered. Radiosurgery was administered for 4–8 weeks following surgical resection. Any patients who had not received previous radiotherapy received open surgical tumor removal, followed by GKRS along with adjuvant chemotherapy. Results: In this prospective clinical study of 49 glioblastoma patients aged 55 years and older, the average lifespan post-histopathological diagnosis was established at 22.3 months (95% CI: 12.0–28.0 months). The median time before disease progression was 14.3 months (95% CI: 13.0–29.7 months). The median duration until the first recurrence after treatment was 15.2 months, with documented cases varying between 4 and 33 months. The Gamma Knife Radiosurgery (GKRS) treatment involved a median marginal recommended dose of 12.5 Gy, targeting an average volume of 5.7 cm³ (range: 1.6–39 cm³). Local recurrence occurred in 21 patients, while distant recurrence was identified in 8 patients. Within the cohort, 34 patients were subjected to further therapeutic approaches, including reoperation, a second GKRS session, the administration of bevacizumab and irinotecan, and PCV chemotherapy. A cognitive function assessment revealed that the patients treated with GKRS experienced significantly less cognitive decline compared to the historical controls, who were treated with conventional radiotherapy. The median MMSE scores declined by 1.9 points over 12 months, and the median MoCA scores declined by 2.9 points. Conclusion: This study demonstrates that Gamma Knife Radiosurgery (GKRS), when integrated with surgical resection and adjuvant chemotherapy, offers a substantial benefit for glioblastoma patients aged 55 years and older. The data reveal that GKRS not only prolongs overall survival and progression-free survival but also significantly reduces cognitive decline compared to conventional radiotherapy. These findings underscore the efficacy and safety of GKRS, advocating for its incorporation into standard treatment protocols for older glioblastoma patients. The potential of GKRS to improve patient outcomes while preserving cognitive function is compelling and warrants further research to optimize and confirm its role in glioblastoma management. Full article

Laryngeal cancer poses a substantial challenge in head and neck oncology, and there is a growing focus on customized medicine techniques. The present state of gene expression indicators in laryngeal cancer and their potential to inform tailored therapy choices are thoroughly examined in this review. We examine significant molecular changes, such as TP53, CDKN2A, PIK3CA, and NOTCH1 mutations, which have been identified as important participants in the development of laryngeal cancer. The study investigates the predictive and prognostic significance of these genetic markers in addition to the function of epigenetic changes such as the methylation of the MGMT promoter. We also go over the importance of cancer stem cell-related gene expression patterns, specifically CD44 and ALDH1A1 expression, in therapy resistance and disease progression. The review focuses on indicators, including PD-L1, CTLA-4, and tumor mutational burden (TMB) in predicting immunotherapy responses, highlighting recent developments in our understanding of the intricate interactions between tumor genetics and the immune milieu. We also investigate the potential for improving prognosis accuracy and treatment selection by the integration of multi-gene expression panels with clinicopathological variables. The necessity for uniform testing and interpretation techniques is one of the difficulties, in implementing these molecular insights into clinical practice, that are discussed. This review seeks to provide a comprehensive framework for promoting personalized cancer therapy by combining the most recent data on gene expression profiling in laryngeal cancer. Molecularly guided treatment options may enhance patient outcomes. Full article

Background/Objectives: Apparent Diffusion Coefficient (ADC) maps in prostate MRI can reveal tumor characteristics, but their accuracy can be compromised by artifacts related with patient motion or rectal gas associated distortions. To address these challenges, we propose a novel approach that utilizes a Generative Adversarial Network to synthesize ADC maps from T2-weighted magnetic resonance images (T2W MRI). Methods: By leveraging contrastive learning, our model accurately maps axial T2W MRI to ADC maps within the cropped region of the prostate organ boundary, capturing subtle variations and intricate structural details by learning similar and dissimilar pairs from two imaging modalities. We trained our model on a comprehensive dataset of unpaired T2-weighted images and ADC maps from 506 patients. In evaluating our model, named AI-ADC, we compared it against three state-of-the-art methods: CycleGAN, CUT, and StyTr2. Results: Our model demonstrated a higher mean Structural Similarity Index (SSIM) of 0.863 on a test dataset of 3240 2D MRI slices from 195 patients, compared to values of 0.855, 0.797, and 0.824 for CycleGAN, CUT, and StyTr2, respectively. Similarly, our model achieved a significantly lower Fréchet Inception Distance (FID) value of 31.992, compared to values of 43.458, 179.983, and 58.784 for the other three models, indicating its superior performance in generating ADC maps. Furthermore, we evaluated our model on 147 patients from the publicly available ProstateX dataset, where it demonstrated a higher SSIM of 0.647 and a lower FID of 113.876 compared to the other three models. Conclusions: These results highlight the efficacy of our proposed model in generating ADC maps from T2W MRI, showcasing its potential for enhancing clinical diagnostics and radiological workflows. Full article

Background: Acute Kidney Injury (AKI) is a condition that affects a significant proportion of acutely unwell patients and is associated with a high mortality rate. Patients undergoing haemopoietic stem cell transplantation (HSCT) are in an extremely high group for AKI. Identifying a biomarker or panel of markers that can reliably identify at-risk individuals undergoing HSCT can potentially impact management and outcomes. Early identification of AKI can reduce its severity and improve prognosis. We evaluated the urinary Liver type fatty acid binding protein (L-FABP), a tubular stress and injury biomarker both as an ELISA and a point of care (POC) assay for AKI detection in HSCT. Methods: 85 patients that had undergone autologous and allogenic HSCT (35 and 50, respectively) had urinary L-FABP (uL-FABP) measured by means of a quantitative ELISA and a semi-quantitative POC at baseline, day 0 and 7 post-transplantation. Serum creatinine (SCr) was also measured at the same time. Patients were followed up for 30 days for the occurrence of AKI and up to 18 months for mortality. The sensitivity and specificity of uL-FABP as an AKI biomarker were evaluated and compared to the performance of sCr using ROC curve analysis and logistic regression. Results: 39% of participants developed AKI within 1 month of their transplantation. The incidence of AKI was higher in the allogenic group than in the autologous HTSC group (57% vs. 26%, p = 0.008) with the median time to AKI being 25 [range 9-30] days. This group was younger (median age 59 vs. 63, p < 0.001) with a lower percentage of multiple myeloma as the primary diagnosis (6% vs. 88%, p < 0.001). The median time to AKI diagnosis was 25 [range 9–30] days. uL-FABP (mcg/gCr) at baseline, day of transplant and on the 7th day post-transplant were 1.61, 5.39 and 10.27, respectively, for the allogenic group and 0.58, 4.36 and 5.14 for the autologous group. Both SCr and uL-FABP levels rose from baseline to day 7 post-transplantation, while the AUC for predicting AKI for baseline, day 0 and day 7 post-transplant was 0.54, 0.59 and 0.62 for SCr and for 0.49, 0.43 and 0.49 uL-FABP, respectively. Univariate logistic regression showed the risk of AKI to be increased in patients with allogenic HSCT (p = 0.004, 95%CI [0.1; 0.65]) and in those with impaired renal function at baseline (p = 0.01, 95%CI [0.02, 0.54]). The risk of AKI was also significantly associated with SCr levels on day 7 post-transplant (p = 0.03, 95%CI [1; 1.03]). Multivariate logistic regression showed the type of HSCT to be the strongest predictor of AKI at all time points, while SCr levels at days 0 and 7 also correlated with increased risk in the model that included uL-FABP levels at the corresponding time points. The POC device for uL-FABP measurement correlated with ELISA (p < 0.001, Spearman ‘correlation’ = 0.54) Conclusions: The urinary biomarker uL-FABP did not demonstrate an independent predictive value in the detection of AKI at all stages. The most powerful risk predictor of AKI in this setting appears to be allograft recipients and baseline renal impairment, highlighting the importance of clinical risk stratification. Urinary L-FAPB as a POC biomarker was comparable to ELISA, which provides an opportunity for simple and rapid testing. However, the utility of LFABP in AKI is unclear and needs further exploration. Whether screening through rapid testing of uL-FABP can prevent or reduce AKI severity is unknown and merits further studies. Full article

(1) Background: Does the variation in sequential development times of embryos, observed through time-lapse monitoring, between the two study groups play a role in predicting pregnancy success? (2) Methods: The prospective double-arm study was to identify the morphokinetic parameters specific to embryos that were capable of implanting and were conducted on 89 embryos cultured in the Esco Miri time-lapse incubator, divided into two groups: Lot A, consisting of 57 embryos that successfully implanted and resulted in life birth rate (LBR), and Lot B (NLB), comprising 32 embryos that did not implant, leading to a negative beta-hCG outcome. (3) Results: Baseline characteristics, including female age, were not found to be statistically significant (p > 0.01). In contrast, there is a highly statistically significant difference concerning oocytes (p = 0.0029). Morphokinetic variables represented by sequential culture times were not statistically significant (p > 0.01) when comparing the two groups. However, the negative mean differences between these parameters suggest that the times for Lot A are better (shorter) than those for Lot B. While not statistically significant, these differences may still have practical significance. In the case of grading, the difference is considered to be extremely statistically significant (p < 0.01). (4) Conclusions: Although there are no statistically significant differences in sequential timings (p > 0.01) between the two groups, there are parameters indicating predictive potential for exploring pregnancy in embryo morphokinetics. Full article

Background: Recent data from European studies (EUROASPIRE V, DA VINCI, SANTORINI) indicate that achieving the LDL cholesterol (LDL-C) target in patients at very high cardiovascular risk is uncommon. Additionally, using a combination therapy involving statins and ezetimibe remains infrequent. Methods: A single-center assessment of a pre-defined lipid lowering treatment algorithm’s effectiveness at achieving the LDL-C target in patients at very high cardiovascular risk one month and one year after hospitalization. Results: 81 patients were included, all in secondary prevention. The average age of the patient was 66.9 years, and the main cardiovascular risk factors included hypertension, diabetes mellitus, and smoking history. Following the predefined lipid-lowering algorithm specific to our study, which involves initiating high-intensity statin therapy or a combination of statin and ezetimibe depending on initial LDL-C levels and patient history; 30 (37%) patients initiated high-intensity statin therapy (Atorvastatin (40 mg, 80 mg) or Rosuvastatin (20 mg, 40 mg)), while 51 (63%) started combination therapy with high-intensity statin and ezetimibe 10 mg. After one year, 57 (70.4%) remained adherent to their initial treatment, achieving a mean LDL-C of 49.5 ± 16.9 mg/dL, with 36 (63.2%) of them reaching the LDL-C target of <55 mg/dL. A total of 13 patients discontinued treatment, and 9 were lost to follow-up, withdrew from the study, or died. Conclusion: Initiating dual statin and ezetimibe therapy or high-intensity statin therapy early, based on the expected treatment efficacy, holds the potential to more rapidly and effectively achieve LDL-C targets in a larger proportion of very high-risk cardiovascular patients. Full article

Background: Performing emergency surgery for bowel obstruction continues to place a significant strain on the healthcare system. Conventional assessment methods for outcomes in bowel obstruction cases often concentrate on isolated factors, and the evaluation of results for individuals with bowel obstruction remains poorly studied. This study aimed to examine the risk factors associated with major postoperative complications. Methods: We retrospectively analyzed 99 patients undergoing surgery from 2015 to 2022. We divided the patients into two groups: (1) benign-related obstruction (n = 68) and (2) cancer-related obstruction (n = 31). We used logistic regression, KNN, and XGBOOST. We calculated the receiver operating characteristic curve and accuracy of the model. Results: Colon obstructions were more frequent in the cancer group (p = 0.005). Operative time, intestinal resection, and stoma were significantly more frequent in the cancer group. Major complications were at 41% for the cancer group vs. 20% in the benign group (p = 0.03). Uni- and multivariate analysis showed that the significant risk factors for major complications were cancer-related obstruction and CRP. The best model was KNN, with an accuracy of 0.82. Conclusions: Colonic obstruction is associated with tumor-related blockage. Malignant cancer and an increase in C-reactive protein (CRP) are significant risk factors for patients who have undergone emergency surgery due to major complications. KNN could improve the process of counseling and the perioperative management of patients with intestinal obstruction in emergency settings. Full article

Introduction: The study of facial profiles in the dental field is very important for the diagnosis and the dental and orthodontic treatment plan. The aim of this study is to analyze the three-dimensional morphology of the faces of 269 growing patients with Class I and II occlusions, focusing on children aged between 6 and 9 years old. The analysis was conducted using a non-invasive computerized system, which allowed for the automatic collection of facial landmarks and the subsequent reconstruction of three-dimensional coordinates. Materials and methods: The sample comprised 269 children within the specified age range. Each child’s facial features were captured using the non-invasive computerized system, which utilized two infrared CCD cameras, real-time hardware for label recognition, and software for three-dimensional landmark reconstruction. Sixteen cutaneous facial landmarks were automatically collected for each participant. From these landmarks, 10 angular and 15 linear measurements, as well as five direct distance rates, were derived. The mean values for each age class were calculated separately for children with bilateral Angle Class I occlusion and compared with those for children with bilateral Class II occlusion. In all children, the left and right occlusal classes were measured as suggested by Katz. Results: The analysis revealed notable differences, primarily in the three-dimensional angular measurements between children with Class I and II occlusions. Specifically, Class II children exhibited more convex faces in the sagittal plane and a less prominent lower jaw compared to Class I children. However, no significant differences were observed in linear measurements, except for the lower facial height rate, which varied inconsistently across age groups between the two occlusion types. Discussion and Conclusions: the findings of this research highlight distinct three-dimensional facial morphological differences between children with Class I and II occlusions. While Class II children tended to have more convex facial profiles and less prominent lower jaws, linear measurements showed minimal variation between the two occlusion types. These results underscore the importance of three-dimensional analysis in understanding facial morphology in growing patients with different occlusal patterns. Full article

Background/Objectives: This study evaluates the impact of anti-vascular endothelial growth factor (anti-VEGF) treatment on neovascular age-related macular degeneration (nAMD) with and without pigment epithelial detachment (PED) over a one-year period. Methods: Conducted at a tertiary referral center in Taiwan, this retrospective analysis included 88 eyes treated with intravitreal aflibercept injections. Patients were categorized into four groups based on the presence or absence of PED at baseline and 12 months post-treatment. Results: Significant reductions in central macular thickness (CMT) and PED height were observed, although no statistical difference was found in best-corrected visual acuity (BCVA). The presence or type of PED did not negatively impact visual outcomes. Among nAMD patients with persistent PED throughout the first year of anti-VEGF treatment, linear regression analysis showed that mixed-type PED revealed poor final BCVA compared to those with serous PED. The analysis also identified older age and poorer initial BCVA as predictors of less favorable visual outcomes. Conclusions: This study highlights the effectiveness of anti-VEGF therapy in real-world settings and offers insights into factors influencing visual outcomes for nAMD patients with PED. Full article

Background and Objectives: The aim of this study was to evaluate the influence of abutment angulation, types, and bone quality on fatigue performance in dental implant systems. Materials and Methods: Three-dimensional models of maxillary 3-unit fixed implant-supported prostheses were analyzed. Abutments with different angles and types were used. Healthy bone (Hb) and resorbed bone (Rb) were used. Conducted on implants, a force of 150 N was applied obliquely, directed from the palatal to the buccal aspect, at a specific angle of 30 degrees. The stress distribution and fatigue performance were then evaluated considering the types of bone used and the angles of the three different abutments. The simulation aspect of the research was carried out utilizing Abaqus 2020 software. Results: In all models, fatigue strengths in healthy bone were higher than in resorbed bone. Maximum stress levels were seen in models with angled implants. In almost all models with resorbed bone, fatigue performances were slightly lower. Conclusions: Increasing the abutment angle has been shown to increase stress levels and decrease fatigue performance in the adjacent bone and along the implant–abutment interface. In general, implants applied to healthy bone were found to have a higher success rate. It has also been suggested that multiunit abutments have beneficial effects on stress distribution and fatigue performance compared to resin cemented abutments. The type or angle of abutment and the quality of the bone can lead to biomechanical changes that affect the force distribution within the bone structure surrounding the implant. Clinicians can influence the biomechanical environment of the implant site by varying the abutment angle and type to suit the condition of bone health, potentially affecting the long-term success of implant treatment. Full article

Background and Objectives: The significance of periodontal disease as a public health issue prompts the exploration of effective treatments, including the potential use of tocopherol (Vitamin E) due to its anti-inflammatory and antioxidant properties. Materials and Methods: The PICO statement (Population, Intervention, Comparator, Outcome) was as follows: In patients with periodontal disease, does tocopherol (Vitamin E) supplementation compared to no supplementation or insufficient Vitamin E intake improve clinical outcomes such as gingival inflammation, pocket depth, and clinical attachment levels? This study searched through PubMed, Scopus, and Web of Science up to June 2024 focused on studies involving human subjects with various forms of periodontal disease, analyzing the impact of tocopherol through dietary or supplementary intake. Primary outcomes evaluated included improvements in gingival inflammation, pocket depth, and clinical attachment levels, with data synthesis conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Quality assessment and risk of bias were meticulously performed for the included observational studies and randomized controlled trials. Results: The meta-analysis incorporated 8 studies that were used for data extraction, totaling 12,832 patients, revealing a heterogeneous response to tocopherol supplementation, with a pooled odds ratio for efficacy in reducing periodontal disease severity at about 0.97 (95% CI: 0.96–0.98). Noteworthy findings indicated a statistically significant increase in clinical attachment loss and pocket depth with odds ratios ranging from 1.15 to 9.33 when Vitamin E was insufficient. However, the considerable heterogeneity (I² = 88.35%) underscores variations in tocopherol’s effectiveness across different populations and study designs. Conclusions: While tocopherol supplementation shows a modest benefit in managing periodontal disease, particularly in reducing clinical attachment levels and pocket depth, the variability in outcomes emphasizes the necessity for more research to establish standardized treatment protocols and dosages. Full article

Background: Aneurysmal subarachnoid hemorrhage (SAH) predominantly affects women, accounting for 65% of cases. Women have a 1.3 times higher relative risk than men, with the incidence rising particularly in women aged 55–85 years. Women also have a higher prevalence of unruptured intracranial aneurysms (IAs), especially after the age of 50 years, and are at greater risk of aneurysm growth and rupture. This study aimed to isolate the influence of sex on rupture rate, bleeding severity, functional outcomes, and complications by using a matched cohort, while also examining the impact of sex on aneurysm localization and multiplicity. Methods: We utilized a retrospectively collected database of 300 patients with 511 IAs. Inclusion criteria included the availability of clinical data and 3D angiography for semi-automatic reconstruction of IA morphology. Female patients and their IA were matched with male patients according to clinical parameters and 21 morphological characteristics using an interactive visual exploration tool for multidimensional matching. Results: Contrary to previously published results, our study found no significant sex differences in rupture rates or vasospasm rates between male and female patients. The severity of SAH, functional outcomes, and complications such as hydrocephalus were also similar in women and men. However, women exhibited a higher prevalence of multiple aneurysms and distinct localization patterns. Conclusions: This study underscores the complex role of sex in IA development and rupture. Although sex-specific biological factors influence aneurysm characteristics, they do not necessarily translate into differences in clinical outcomes. Further research is needed to explore these factors and their impact on aneurysm development and management. Full article

Objective: Prostate tumors, if prostate cancer or adenoma, represent a major public health challenge. Progress in research on inflammation has revealed a connection between inflammation, immunity, and cancer. In this context, this study aimed to find IL-6 signaling systemic abnormalities in the inflammatory tumor microenvironment. Material and methods: This study was case–controlled, multicentered, and included 86 patients, 43 diagnosed with BPH and 43 diagnosed with PCa, between January 2019 and January 2020. The study group was homogenous and the studied parameters were IL-6 complex (IL-6, soluble receptor IL-6R, soluble glycoprotein gp130), acute phase proteins (C reactive protein—CRP, acid alpha1 glycoprotein—AGPA, ferritin, albumin, transferrin), and oxidative stress-associated variables (malondialdehyde—MDA, carbonylated protein—PCO, 8-hydroxy-deoxy guanosine-8-OHdG, total antioxidant status—bTAS). Results: The inflammatory microenvironment determined IL-6 signaling alterations (over-regulation of sIL-6R and suppression of sgp130 in PCa versus BPH), changes in acute phase reaction markers (increased serum levels of CRP, AGPA, ferritin, and decreased serum levels of albumin, transferrin) that were much more evident in PCa compared to BPH, an imbalance between macromolecular oxidative damage (MDA, PCO, 8-OHdG) and endogenous antioxidants (TAS) that was more accentuated in PCa compared with BPH, and a representative association between the sIL-6R/sgp130 ratio and inflammatory/oxidative stress-related factors only in PCa patients. Conclusions: Our study reconfirms the anterior concept that IL-6 promotes prostatic tumorigenesis. In this study, we first demonstrated that a high sIL-6R/sgp130 ratio facilitates prostate malignancy. Full article