J. Pers. Med., Volume 14, Issue 4 (April 2024) – 111 articles

Personalized medicine in kidney transplantation has the potential to improve outcomes and reduce complications. The aim of this study was to investigate the influence of single nucleotide polymorphisms in genes encoding metabolizing enzymes (CYP3A5) and transporters (ABCC2) on clinical outcomes (acute graft failure and/or acute tubular necrosis (ATN)) in kidney transplant recipients (KTR). This was a multicenter, retrospective cohort study where adult KTR who had undergone kidney transplantation between 2020 and 2021 and received tacrolimus-mycophenolate treatment were enrolled in the study. DNA was extracted from collected blood samples using a commercially available kit. CYP3A5*3, ABCC2 -24C>T and ABCC2 3972C>T SNP were determined by polymerase chain reaction. Of the total 39 patients included, nine (23.1%) KTR had an incidence of acute graft failure and/or ATN. A multiple logistic regression showed wildtype ABCC2 -24C>T C allele had a higher risk of developing acute graft rejection and/or ATN compared to the variant allele carriers (adjusted Odd Ratios [aOR]: 27.675, p = 0.038). Recipients who had delayed graft function (aOR: 49.214, p = 0.012) and a history of CMV infection (aOR: 18.097, p = 0.009) were at 49.2 and 18.1-times increased risk for acute graft failure and/or ATN, respectively. The large aOR was inevitable due to the small sample size and required cautious interpretation. This is the first study to determine the effect of the ABCC2 -24C>T genetic polymorphism on clinical outcomes in Malaysian KTR and forms the basis for further work on ABCC2 -24C>T effects in long-term KTR. Full article

Background: This study aimed to compare surgical outcomes between two new robotic single-site myomectomy (RSSM)-complementary techniques: coaxial robotic single-site myomectomy (Coaxial-RSSM) and hybrid robotic single-site myomectomy (Hybrid-RSSM). Methods: Medical records for 132 women undergoing Coaxial-RSSM and 150 undergoing Hybrid-RSSM, consecutively, were retrospectively reviewed. Patient characteristics and surgical outcomes were assessed and compared after propensity score matching (PSM). Results: In the outcomes of PSM, the Coaxial-RSSM group showed significantly reduced blood loss (79.71 vs. 163.75 mL, p < 0.001) and reduced hospital duration (4.18 ± 0.62 vs. 4.63 ± 0.90) relative to the Hybrid-RSSM group. Conversely, Hybrid-RSSM allowed for a shorter operative time compared with Coaxial-RSSM (119.19 vs. 156.01 min, p = 0.007). No conversions to conventional laparoscopy or laparotomy or any need for the multi-site robotic approach occurred in either group. Postoperative complications, including ileus, fever, and wound dehiscence, showed no statistically significant differences between the two groups. Conclusions: Blood loss was lower with Coaxial-RSSM, and operative time was shorter for Hybrid-RSSM. A follow-up prospective study is warranted for more comprehensive comparison of surgical outcomes between the two techniques. Full article

Background: Coronary artery calcification is a predictor of adverse outcomes after percutaneous coronary intervention (PCI). Intravascular lithotripsy (IVL) is a promising tool for the treatment of calcified lesions. The aim of this study was to assess the effectiveness and safety of IVL. Methods: A single-center observational study of PCI procedure, with assessment of the outcomes of patients undergoing PCI using IVL, was performed. Angiographic procedural success was used as the primary effectiveness endpoint. The primary safety endpoint was defined as a composite of cardiac death, myocardial infarction and target vessel revascularization within 30 days. Results: A total of 111 patients were included. Indications for PCI spanned the spectrum of chronic (53.2%) and acute coronary syndromes (43%). Lesion preparation before IVL was performed with non-compliant (42%), cutting or OPN (14.4%) balloons and with atherectomy techniques in 11% of procedures. Intravascular imaging was used in 21.6% of procedures. The primary effectiveness endpoint was achieved in 100% and the primary safety endpoint in 3.6% of procedures. Peri-procedural complications were minimal and successfully resolved. Conclusions: IVL was an effective and safe technique for the treatment of calcified coronary lesions. These findings contribute to the growing body of evidence supporting the use of IVL in the management of these challenging scenarios. Full article

Oxidative stress plays an important role in neurodegenerative diseases, including glaucoma. Therefore, we analyzed if the antioxidant coenzyme Q10 (CoQ10), which is also commercially available, can prevent retinal degeneration induced by hydrogen peroxide (H₂O₂) in a porcine organ culture model. Retinal explants were cultivated for eight days, and H₂O₂ (500 µM, 3 h) induced the oxidative damage. CoQ10 therapy was applied (700 µM, 48 h). Retinal ganglion cells (RGCs) and microglia were examined immunohistologically in all groups (control, H₂O₂, H₂O₂ + CoQ10). Cellular, oxidative, and inflammatory genes were quantified via RT-qPCR. Strong RGC loss was observed with H₂O₂ (p ≤ 0.001). CoQ10 elicited RGC protection compared to the damaged group at a histological (p ≤ 0.001) and mRNA level. We detected more microglia cells with H₂O₂, but CoQ10 reduced this effect (p = 0.004). Cellular protection genes (NRF2) against oxidative stress were stimulated by CoQ10 (p ≤ 0.001). Furthermore, mitochondrial oxidative stress (SOD2) increased through H₂O₂ (p = 0.038), and CoQ10 reduced it to control level. Our novel results indicate neuroprotection via CoQ10 in porcine retina organ cultures. In particular, CoQ10 appears to protect RGCs by potentially inhibiting apoptosis-related pathways, activating intracellular protection and reducing mitochondrial stress. Full article

The field of precision radiation therapy has seen remarkable advancements in both experimental and computational methods. Recent literature has introduced various approaches such as Spatially Fractionated Radiation Therapy (SFRT). This unconventional treatment, demanding high-precision radiotherapy, has shown promising clinical outcomes. A comprehensive computational scheme for SFRT, extrapolated from a case report, is proposed. This framework exhibits exceptional flexibility, accommodating diverse initial conditions (shape, inhomogeneity, etc.) and enabling specific choices for sub-volume selection with administrated higher radiation doses. The approach integrates the standard linear quadratic model and, significantly, considers the activation of the immune system due to radiotherapy. This activation enhances the immune response in comparison to the untreated case. We delve into the distinct roles of the native immune system, immune activation by radiation, and post-radiotherapy immunotherapy, discussing their implications for either complete recovery or disease regrowth. Full article

Orthostatic intolerance is a broad term that represents a spectrum of dysautonomic disorders, including postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH), as manifestations of severe autonomic failure. While the etiology of orthostatic intolerance has not yet fully been uncovered, it has been associated with multiple underlying pathological processes, including peripheral neuropathy, altered renin–aldosterone levels, hypovolemia, and autoimmune processes. Studies have implicated adrenergic, cholinergic, and angiotensin II type I autoantibodies in the pathogenesis of orthostatic intolerance. Several case series have demonstrated that immunomodulation therapy resulted in favorable outcomes, improving autonomic symptoms in POTS and OH. In this review, we highlight the contemporary literature detailing the association of autoimmunity with POTS and OH. Full article

Menopausal status affects the prognoses and consequences of breast cancer. Therefore, this retrospective study aimed to reveal the molecular variation profile differences in breast cancer patients according to their menopausal status, with the hypothesis that the molecular variation profiles will be different at premenopausal and postmenopausal ages. Breast cancer patients (n = 254) who underwent molecular subtyping and QIAseq Human Breast Cancer NGS Panel screening between 2018 and 2022 were evaluated retrospectively. Their menopausal status was defined by age, and those aged 50 years and above were considered postmenopausal. Of the subjects, 58.66% (n = 149) were premenopausal and 41.34% (n = 105) were postmenopausal. The mean age at the time of diagnosis for all patients was 49.31 ± 11.19 years, with respective values of 42.11 ± 5.51 and 59.54 ± 9.01 years for the premenopausal and postmenopausal groups, respectively (p = 0.000). Among premenopausal patients, the percentages of patients in BCa subtypes (luminal A, luminal B-HER2(−), luminal B-HER2(+), HER2 positive, and triple-negative) were determined to be 34.90%, 8.05%, 26.17%, 10.74%, and 20.13%, respectively, while in the postmenopausal group, these values were 39.05%, 16.19%, 24.76%, 6.67%, and 13.33%, respectively (p > 0.05). Considering menopausal status, the distribution of hormone receptors in premenopausal patients was ER(+)/PgR(+) 63.76%, ER(−)/PgR(−) 23.49%, ER(+)/PgR(−) 10.74%, and ER(−)/PgR(+) 2.01%, respectively, while in postmenopausal women, this distribution was observed to be 74.29%, 23.81%, 1.90% and 0.00% in the same order (p = 0.008). The most frequently mutated gene was TP53 in 130 patients (51.18%), followed by PIK3CA in 85 patients (33.46%), BRCA2 and NF1 in 56 patients (22.05%), PTEN in 54 patients (21.26%), and ATR and CHEK2 in 53 patients (20.87%). TP53, PIK3CA, NF1, BRCA2, PTEN, and CHEK2 mutations were more frequently observed in premenopausal patients, while TP53, PIK3CA, BRCA2, BRCA1, and ATR mutations in postmenopausal patients. These findings contribute to a deeper understanding of the underlying causes of breast cancer with respect to menopausal status. This study is the first from Turkey that reflects the molecular subtyping and somatic mutation profiles of breast cancer patients according to menopausal status. Full article

Background: Despite pregnancy’s hypercoagulable state, the correlation between inherited thrombophilia and thrombotic adverse pregnancy outcomes remains uncertain. The objective of this study was to determine the prevalence of inherited thrombophilic polymorphisms among asymptomatic pregnant individuals and to examine their potential correlation with adverse perinatal outcomes. Methods: in this single-center prospective study, 105 healthy pregnant women were included. Genotyping was conducted for factor V Leiden (FVL), prothrombin gene mutation, methylenetetrahydrofolate reductase enzyme (MTHFR) C677T, MTHFR A1298C, and plasminogen activator inhibitor-1 (PAI-1), alongside the assessment of protein C (PC), protein S (PS), and antithrombin (AT) levels. The study analyzed the association between inherited thrombophilic polymorphisms and pregnancy complications linked to placental insufficiency, such as gestational hypertension (GH), preeclampsia (PE), intrauterine death (IUD), fetal growth restriction (FGR), and placental abruption. Results: The prevalence of identifiable thrombophilic polymorphism mutations was 61.9% (95% confidence interval—CI 52.4–70.8%), with the most common single mutation being PAI-1 4G/5G (12/105, 11.4%, 95% CI 6.4–18.5). The most frequent combined mutation was heterozygosity for MTHFR C677T and PAI-1 (12/105, 11.4%, 95% CI 6.4–18.5). Notably, no FVL homozygous carriers or single homozygous and heterozygous carriers for prothrombin polymorphisms were found. Additionally, no deficiencies in PC and AT were detected among participants. Except for homozygosity for PAI-1, none of the studied polymorphisms demonstrated a significant association with pregnancy complications linked to placental insufficiency. Conclusions: The asymptomatic carriers of inherited thrombophilic polymorphisms do not have an increased risk of adverse perinatal outcomes. Full article

Chronic rhinosinusitis with nasal polyposis is a common inflammatory condition, with subtypes like aspirin-exacerbated respiratory disease, allergic fungal rhinosinusitis, and central compartment atopic disease sharing a common type 2 inflammatory pathway. Respiratory biologic therapies have been developed that target type 2 inflammation. In this article, we discuss the use of respiratory biologic therapies for nasal polyposis in general, as well as within the various subtypes of nasal polyps. Further, we discuss future roles of novel biologic therapies targeting type 2 inflammation in nasal polyposis. Full article

In recent years, immuno-oncology has revolutionized the cancer treatment field by harnessing the immune system’s power to counteract cancer cells. While this innovative approach holds great promise for improving cancer outcomes, it also raises important considerations related to fertility and reproductive toxicity. In fact, most young females receiving gonadotoxic anti-cancer treatments undergo iatrogenic ovarian exhaustion, resulting in a permanent illness that precludes the vocation of motherhood as a natural female sexual identity. Although commonly used, oocyte cryopreservation for future in vitro fertilization and even ovarian cortex transplantation are considered unsafe procedures in cancer patients due to their oncogenic risks; whereas, ovarian stem cells might support neo-oogenesis, providing a novel stemness model of regenerative medicine for future fertility preservation programs in oncology. Recent scientific evidence has postulated that immune checkpoint inhibitors (ICIs) might in some way reduce fertility by inducing either primary or secondary hypogonadism, whose incidence and mechanisms are not yet known. Therefore, considering the lack of data, it is currently not possible to define the most suitable FP procedure for young patients who are candidates for ICIs. In this report, we will investigate the few available data concerning the molecular regulation of ICI therapy and their resulting gonadal toxicity, to hypothesize the most suitable fertility preservation strategy for patients receiving these drugs. Full article

Respiratory malignancies, encompassing cancers affecting the lungs, the trachea, and the bronchi, pose a significant and dynamic public health challenge. Given that air pollution stands as a significant contributor to the onset of these ailments, discerning the most detrimental agents becomes imperative for crafting policies aimed at mitigating exposure. This study advocates for the utilization of explainable artificial intelligence (XAI) methodologies, leveraging remote sensing data, to ascertain the primary influencers on the prediction of standard mortality rates (SMRs) attributable to respiratory cancer across Italian provinces, utilizing both environmental and socioeconomic data. By scrutinizing thirteen distinct machine learning algorithms, we endeavor to pinpoint the most accurate model for categorizing Italian provinces as either above or below the national average SMR value for respiratory cancer. Furthermore, employing XAI techniques, we delineate the salient factors crucial in predicting the two classes of SMR. Through our machine learning scrutiny, we illuminate the environmental and socioeconomic factors pertinent to mortality in this disease category, thereby offering a roadmap for prioritizing interventions aimed at mitigating risk factors. Full article

A positive fluid balance may evolve to fluid overload and associate with organ dysfunctions, weaning difficulties, and increased mortality in ICU patients. We explored whether individualized fluid management, assessing fluid responsiveness via a passive leg-raising maneuver (PLR) before a spontaneous breathing trial (SBT), is associated with less extubation failure in ventilated patients with a high fluid balance admitted to the ICU after liver transplantation (LT). We recruited 15 LT patients in 2023. Their postoperative fluid balance was +4476 {3697, 5722} mL. PLR maneuvers were conducted upon ICU admission (T1) and pre SBT (T2). Cardiac index (CI) changes were recorded before and after each SBT (T3). Seven patients were fluid-responsive at T1, and twelve were responsive at T2. No significant differences occurred in hemodynamic, respiratory, and perfusion parameters between the fluid-responsive and fluid-unresponsive patients at any time. Fluid-responsive patients at T1 and T2 increased their CI during SBT from 3.1 {2.8, 3.7} to 3.7 {3.4, 4.1} mL/min/m² (p = 0.045). All fluid-responsive patients at T2 were extubated after the SBTs and consolidated extubation. Two out of three of the fluid-unresponsive patients experienced weaning difficulties. We concluded that fluid-responsive patients post LT may start weaning earlier and achieve successful extubation despite a high postoperative fluid balance. This highlights the profound impact of personalized assessments of cardiovascular state on critical surgical patients. Full article

(1) Background: Performance after Cochlear Implantation (CI) can vary depending on numerous factors. This study aims to investigate how meningitis or otosclerosis can influence CI performance. (2) Methods: Retrospective analysis of CI performance in patients with etiological diagnosis of meningitis or otosclerosis, comparing the etiologies and analyzing the image findings, along with electrode array insertion status and technique. (3) Results: Speech recognition in CI patients with otosclerosis improves faster than in patients with meningitis. Other features such as radiological findings, degree of cochlear ossification, surgical technique used and total or partial insertion of electrodes do not seem to be directly related to speech recognition test performance. (4) Conclusions: Patients should be warned that their postoperative results have a strong correlation with the disease that caused their hearing loss and that, in cases of meningitis, a longer duration of speech–language training may be necessary to reach satisfactory results. Full article

(1) Background: Although the association between psoriasis and atopic dermatitis (AD) is reported in the literature, scarce data are known about the efficacy of biologic therapy (including TNF and IL-17 inhibitors) in patients with psoriatic arthritis (PsA) and concomitant AD. (2) Objective: We aimed to explore AD in patients with PsA undergoing biologics for their active disease, focusing on prevalence and clinical and potential therapeutic implications. (3) Material and methods: We performed a retrospective analysis of 64 patients with PsA receiving various biological agents, followed-up in an academic outpatient rheumatology department up to 10 years. (4) Results: Atopic diseases were reported in about one third of cases, with a higher incidence of AD (10 cases; 52.6%) vs. atopic rhinitis (6 cases; 31.6%) and allergic asthma (3 cases; 15.8%). Three morphological patterns of AD were recognized including chronic prurigo (3 cases), a chronic lichen simplex (1 case), and eczemas (6 cases). All PsA with concomitant AD displayed a late onset of skin atopy (in their adult life) and demonstrated a specific profile (younger), from urban settings, equally distributed among genders, and requiring switching to a higher number of biologics to achieve disease control. (5) Conclusion: PsA and AD may coexist, requiring special attention when selecting the optimal biologic agent. Full article

Introduction: The interferon pathway plays a critical role in triggering the immune response to SARS-CoV-2, and these gene variants may be involved in the severity of COVID-19. This study aimed to analyze the frequency of three gene variants of OAS and RNASEL with the occurrence of COVID-19 symptoms and disease outcome. Methods: This cross-sectional study included 104 patients with SARS-CoV-2 infection, of which 34 were asymptomatic COVID-19, and 70 were symptomatic cases. The variants rs486907 (RNASEL), rs10774671 (OAS1), rs1293767 (OAS2), and rs2285932 (OAS3) were screened and discriminated using a predesigned 5′-nuclease assay with TaqMan probes. Results: Patients with the allele C of the OAS2 gene rs1293767 (OR = 0.36, 95% CI: 0.15–0.83, p = 0.014) and allele T of the OAS3 gene rs2285932 (OR = 0.39, 95% CI: 0.2–0.023, p = 0.023) have lower susceptibility to developing symptomatic COVID-19. The genotype frequencies (G/G, G/C, and C/C) of rs1293767 for that comparison were 64.7%, 29.4%, and 5.9% in the asymptomatic group and 95.2%, 4.8%, and 0% in severe disease (p < 0.05). Conclusions: Our data indicate that individuals carrying the C allele of the OAS2 gene rs1293767 and the T allele of the OAS3 gene rs2285932 are less likely to develop symptomatic COVID-19, suggesting these genetic variations may confer a protective effect among the Mexican study population. Furthermore, the observed differences in genotype frequencies between asymptomatic individuals and those with severe disease emphasize the potential of these variants as markers for disease severity. These insights enhance our understanding of the genetic factors that may influence the course of COVID-19 and underscore the potential for genetic screening in identifying individuals at increased risk for severe disease outcomes. Full article

Insulin gene mutations affect the structure of insulin and are considered a leading cause of neonatal diabetes and permanent neonatal diabetes mellitus PNDM. These mutations can affect the production and secretion of insulin, resulting in inadequate insulin levels and subsequent hyperglycemia. Early discovery or prediction of PNDM can aid in better management and treatment. The current study identified potential deleterious non-synonymous single nucleotide polymorphisms nsSNPs in the INS gene. The analysis of the nsSNPs in the INS gene was conducted using bioinformatics tools by implementing computational algorithms including SIFT, PolyPhen2, SNAP2, SNPs & GO, PhD-SNP, MutPred2, I-Mutant, MuPro, and HOPE tools to investigate the prediction of the potential association between nsSNPs in the INS gene and PNDM. Three mutations, C96Y, P52R, and C96R, were shown to potentially reduce the stability and function of the INS protein. These mutants were subjected to MDSs for structural analysis. Results suggested that these three potential pathogenic mutations may affect the stability and functionality of the insulin protein encoded by the INS gene. Therefore, these changes may influence the development of PNDM. Further researches are required to fully understand the various effects of mutations in the INS gene on insulin synthesis and function. These data can aid in genetic testing for PNDM to evaluate its risk and create treatment and prevention strategies in personalized medicine. Full article

Bilateral scaphoid fractures are rare lesions, warranting a review to synthesize current knowledge, identify gaps, and suggest research directions. Two authors, adhering to PRISMA guidelines, in January 2024 identified 16 case reports (1976–2023). Data extraction included demographics, injury mechanisms, associated injuries, fracture sites, treatments, and outcomes. Among 121 initial outcomes, 16 articles met the criteria, predominantly affecting young people (93.75% males, mean age 22 years). High-energy traumas (75%) often caused associated wrist injuries (68.75%). Most fractures required surgical intervention (68.75%), primarily headless compression screws. Bilateral scaphoid fractures, which are rare but associated with high-energy traumas, commonly involve wrist injuries. Surgical management is often necessary, yielding better outcomes with fewer complications. Further research is essential to understand the epidemiology, optimal management, and long-term results. Early diagnosis and appropriate treatment are crucial for preventing complications and ensuring favorable patient outcomes. Full article

Olfactory neuroblastoma (ONB) is an uncommon neuroendocrine malignancy arising from the olfactory neuroepithelium. ONB frequently presents with nonspecific sinonasal complaints, including nasal obstruction and epistaxis, and diagnosis can be obtained through a combination of physical examination, nasal endoscopy, and computed tomography and magnetic resonance imaging. Endoscopic resection with negative margins, with or without craniotomy, as necessary, is the standard of care for definitive treatment of ONB. Regional metastasis to the neck is often detected at presentation or may occur in a delayed fashion and should be addressed through elective neck dissection or radiation. Adjuvant radiotherapy should be considered, particularly in the case of high grade or tumor stage, as well as positive surgical margins. Systemic therapy is an area of active investigation in both the neoadjuvant and adjuvant setting, with many advocating in favor of induction chemotherapy for significant orbital or intracranial involvement prior to surgical resection. Various targeted immunotherapies are currently being studied for the treatment of recurrent or metastatic ONB. Prolonged locoregional and distant surveillance are indicated following definitive treatment, given the tendency for delayed recurrence and metastasis. Full article

Background: The early prediction of the need for massive transfusions (MTs) and the preparation of blood products are essential for managing patients with primary postpartum hemorrhage (PPH). Thromboelastography (TEG) enables a thorough evaluation of coagulation status and is useful for guiding the treatment of hemorrhagic events in various diseases. We investigated the role of TEG in predicting the need for MT in patients with primary PPH. Methods: A retrospective observational study was conducted in the emergency department (ED) of a university-affiliated, tertiary referral center between November 2015 and August 2023. TEG was performed upon admission. We defined MT as the requirement for transfusion of more than 10 units of packed red blood cells within the first 24 h. The primary outcome was the need for MT. Results: Among the 184 patients with initial TEG, 34 (18.5%) required MT. Except for lysis after 30 min, the MT and non-MT groups had significantly different TEG values. Based on multivariate analysis, an angle < 60 was an independent predictor of MT (odds ratio (OR) 7.769; 95% confidence interval (CI), 2.736–22.062), along with lactate (OR, 1.674; 95% CI, 1.218–2.300) and shock index > 0.9 (OR, 4.638; 95% CI, 1.784–12.056). Alpha angle < 60 degrees indicated the need for MT with 73.5% sensitivity, 72.0% specificity, and 92.3% negative predictive value. Conclusions: Point-of-care testing of TEG has the potential to be a useful tool in accurately predicting the necessity for MT in ED patients with primary PPH at an early stage. Full article

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease, yet its current treatments are limited to stopping disease progression. Moreover, the effectiveness of these treatments remains uncertain due to the heterogeneity of the disease. Therefore, it is essential to identify disease subtypes at a very early stage. Current data-driven approaches can be used to classify subtypes during later stages of AD or related disorders, but making predictions in the asymptomatic or prodromal stage is challenging. Furthermore, the classifications of most existing models lack explainability, and these models rely solely on a single modality for assessment, limiting the scope of their analysis. Thus, we propose a multimodal framework that utilizes early-stage indicators, including imaging, genetics, and clinical assessments, to classify AD patients into progression-specific subtypes at an early stage. In our framework, we introduce a tri-modal co-attention mechanism (Tri-COAT) to explicitly capture cross-modal feature associations. Data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (slow progressing = 177, intermediate = 302, and fast = 15) were used to train and evaluate Tri-COAT using a 10-fold stratified cross-testing approach. Our proposed model outperforms baseline models and sheds light on essential associations across multimodal features supported by known biological mechanisms. The multimodal design behind Tri-COAT allows it to achieve the highest classification area under the receiver operating characteristic curve while simultaneously providing interpretability to the model predictions through the co-attention mechanism. Full article

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, usually occurring in the background of chronic liver disease. HCC lethality rate is in the third highest place in the world. Patients with HCC have concealed early symptoms and possess a high-level of heterogeneity. Once diagnosed, most of the tumors are in advanced stages and have a poor prognosis. The sensitivity and specificity of existing detection modalities and protocols are suboptimal. HCC calls for more sophisticated and individualized therapeutic regimens. Liquid biopsy is non-invasive, repeatable, unaffected by location, and can be monitored dynamically. It has emerged as a useable aid in achieving precision malignant tumor treatment. Circulating tumor cells (CTCs), circulating nucleic acids, exosomes and tumor-educated platelets are the commonest components of a liquid biopsy. It possesses the theoretical ability to conquer the high heterogeneity and the difficulty of early detection for HCC patients. In this review, we summarize the common enrichment techniques and the clinical applications in HCC for different liquid biopsy components. Tumor recurrence after HCC-related liver transplantation is more insidious and difficult to treat. The clinical use of liquid biopsy in HCC-related liver transplantation is also summarized in this review. Full article

Background: The ratio of neutrophils to lymphocytes [NLR] is one of the most accepted prognostic indices and demonstrates a positive correlation with the severity of a disease. Given that probiotics exerted immunomodulatory properties and thus positively affected lymphocytopenia induction in severely ill patients, we performed a post hoc analysis in the ProVAP protocol to investigate whether probiotics affected the prognostication of NLR in respect to ventilator-associated pneumonia in multi-trauma patients. This cohort mandatorily involved severe traumatic brain injury patients. Methods: The white blood cell data of all patients, after being retrieved for the days 0 and 7, were statistically assessed in respect to neutrophils, lymphocytes and NLR among the 4 sub-groups of the study: placebo/no-VAP, placebo/VAP, probiotics/no-VAP, and probiotics/VAP. Results: Lymphopenia was dominant in placebo sub-groups, while an increased level of lymphocytes was prominent in probiotics sub-groups. This resulted in an increase [p = 0.018] in the NLR value in the probiotics/VAP group in relation to the probiotics/no-VAP cohort; this was an increase of half the value of the placebo/VAP [p < 0.001], while the NLR value in placebo/no-VAP group increased almost four-fold in relation to probiotics/no-VAP [p < 0.001]. Additionally, the ROC curve for probiotic-treated patients revealed a NLR7 cut-off value of 7.20 as a prognostic factor of VAP (AUC: 78.6%, p = 0.015, 95% CI: 62.6–94.5%), having a high specificity of 90.2% and a sensitivity of 42.9%. Conclusions: NLR may considered a credible prognostic biomarker in multi-trauma patients since it can evaluate the immunomodulatory benefits of probiotic treatment. However, the results of the present post hoc analysis should be interpreted meticulously until further evaluation, since they may be basically species- or strain-specific. Full article

Precision medicine (PM), also termed stratified, individualised, targeted, or personalised medicine, embraces a rapidly expanding area of research, knowledge, and practice. It brings together two emerging health technologies to deliver better individualised care: the many “-omics” arising from increased capacity to understand the human genome and “big data” and data analytics, including artificial intelligence (AI). PM has the potential to transform an individual’s health, moving from population-based disease prevention to more personalised management. There is however a tension between the two, with a real risk that this will exacerbate health inequalities and divert funds and attention from basic healthcare requirements leading to worse health outcomes for many. All areas of medicine should consider how this will affect their practice, with PM now strongly encouraged and supported by government initiatives and research funding. In this review, we discuss examples of PM in current practice and its emerging applications in primary care, such as clinical prediction tools that incorporate genomic markers and pharmacogenomic testing. We look towards potential future applications and consider some key questions for PM, including evidence of its real-world impact, its affordability, the risk of exacerbating health inequalities, and the computational and storage challenges of applying PM technologies at scale. Full article

(1) Objective: The main aims of our study were to explore the drug survival and effectiveness of secukinumab in patients with axial spondyloarthritis (axSpA). (2) Methods: We underwent a retrospective analysis of consecutive axSpA treated with secukinumab as a first line of biologics or at switch in a biologic-experienced population. Efficacy data, indicating improvement in inflammation parameters (such as C-reactive protein and erythrocyte sedimentation rate) and disease activity scores (such as Ankylosing Spondylitis Disease Activity Score [ASDAS-CRP], Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), and patient-reported outcomes (pain), were assessed at 6, 12, 24, 36 and 48 months. The drug survival rate, dropout rate and discontinuation reasons (efficacy versus safety) of secukinumab were assessed in subgroup analysis (axSpA with and without exposure to biologics). (3) Results: In total, 46 patients were exposed to the IL-17A inhibitor secukinumab. The drug survival for axSpA patients 59.7% at 12 months and 31.3% at 24 months. There were no statistically significant differences in the median drug survival between biologic-naïve versus biologic-experienced subgroups. (4) Conclusions: Secukinumab has demonstrated effectiveness and safety in treating a cohort of axSpA patients in real-world settings, with a notable retention rate of the drug. Full article

Purpose: Errors and incidents may occur at any point within radiotherapy (RT). The aim of the present retrospective analysis is to evaluate the impact of a customized ARIA Visual Care Path (VCP) on quality assurance (QA) for the RT process. Materials and Methods: The ARIA VCP was implemented in June 2019. The following tasks were customized and independently verified (by independent checks from radiation oncologists, medical physics, and radiation therapists): simulation, treatment planning, treatment start verification, and treatment completion. A retrospective analysis of 105 random and unselected patients was performed, and 945 tasks were reviewed. Patients’ reports were categorized based on treatment years period: 2019–2020 (A); 2021 (B); and 2022–2023 (C). The QA metrics included data for timeliness of task completion and data for minor and major incidents. The major incidents were defined as incorrect prescriptions of RT dose, the use of different immobilization systems during RT compared to the simulation, the absence of surface-guided RT data for patients’ positioning, incorrect dosimetric QA for treatment plans, and failure to complete RT as originally planned. A sample size of approximately 100 was able to obtain an upper limit of 95% confidence interval below 5–10% in the case of zero or one major incident. Results: From June 2019 to December 2023, 5300 patients were treated in our RT department, an average of 1300 patients per year. For the purpose of this analysis, one hundred and five patients were chosen for the study and were subsequently evaluated. All RT staff achieved a 100% compliance rate in the ARIA VCP timely completion. A total of 36 patients were treated in Period A, 34 in Period B, and 35 in Period C. No major incidents were identified, demonstrating a major incident rate of 0.0% (95% CI 0.0–3.5%). A total of 26 out of 945 analyzed tasks (3.8%) were reported as minor incidents: absence of positioning photo in 32 cases, lack of patients’ photo, and absence of plan documents in 4 cases. When comparing periods, incidents were statistically less frequent in Period C. Conclusions: Although the present analysis has some limitations, its outcomes demonstrated that software for the RT workflow, which is fully integrated with both the record-and-verify and treatment planning systems, can effectively manage the patient’s care path. Implementing the ARIA VCP improved the efficiency of the RT care path workflow, reducing the risk of major and minor incidents. Full article

The nasal cavity constitutes the foremost portion of the respiratory system, composed of the anterior nasal aperture, nostrils, and choanae. It has an intricate anatomical structure since it has various functions, such as heat exchange, humidification, and filtration. Accordingly, clinical symptoms related to the nose, such as nasal congestion, snoring, and nasal septal deviation, are closely linked to the complex anatomical structure of the nasal cavity. Thus, the nasal cavity stands as a paramount structure in both forensic and clinical contexts. The majority of relevant studies have performed comparisons between sexes, with studies making comparisons according to the FI and NI only and examining relative percentages. Furthermore, the nasal cavity was measured in 2D, and not 3D, in most cases. In this study, we conducted a 3D modeling and anthropometric assessment of the nasal cavity using a 3D analysis software. Furthermore, we aimed to investigate whether the size of the nasal cavity differs according to sex, facial index (FI), and nasal index (NI). We retrospectively reviewed the cone-beam computed tomography (CBCT) data of 100 participants (50 males, 50 females) aged 20–29 years who visited the dental hospital of Dankook University (IRB approval no. DKUDH IRB 2020-01-007). Our findings showed that nasal cavity sizes generally differed according to sex, FI, and NI. These findings provide implications for performing patient-tailored surgeries in clinical practice and conducting further research on the nasal cavity. Therefore, we believe that our study makes a significant contribution to the literature. Full article

Background: Nasal polyps (NPs) represent the end-stage manifestation of chronic rhinosinusitis (CRS), a relatively common pathological condition encountered in all ages of life. Methodology: The aim of our study was to evaluate the histological features and inflammatory cellular components of NPs in a retrospective cohort (143 cases) of pediatric, adult and elderly populations in order to discuss the possible morphological age-related differences statistically documented. Results: In the pediatric group, the inflammatory infiltrate presented many eosinophils mixed with lymphocytes, while in the adult population, lymphocytes and plasma cells were mainly evident, frequently with a perivascular distribution or with the formation of subepithelial lymphoid nodules. In the elderly population, inflammation was less evident and was associated with cavernous-like angecthatic structures with thrombotic stratification. Nearly all morphological findings exhibited statistically significant values among differently aged subgroups. Conclusions: Our results support the presence of histological specificities of NPs at different ages of life, providing new insight into the etiopathogenesis of NPs. The future role of biological therapies, mainly in cases refractory to already available standard medical and surgical treatments, may be analyzed by a prospective study using a larger cohort with a long-term evaluation also in relation to a possible relapse. Full article

Introduction: Hematopoietic stem cell transplantation (HSCT) recipients are at increased risk of cardiovascular diseases. In our study, we aimed to find subclinical changes in myocardial tissue after HSCT with the help of cardiovascular magnetic resonance (CMR) tissue imaging techniques. Methods: The data of 44 patients undergoing autologous and allogeneic HSCT in the Hospital of Lithuanian University of Health Sciences Kaunas Clinics from October 2021 to February 2023 were analyzed. Bioethics approval for the prospective study was obtained (No BE-2-96). CMR was performed two times: before enrolling for the HSCT procedure (before starting mobilization chemotherapy for autologous HSCT and before starting the conditioning regimen for allogeneic HSCT) and 12 ± 1 months after HSCT. LV end-diastolic volume, LV end-systolic volume, LV mass and values indexed to body surface area (BSA), and LV ejection fraction were calculated. T1 and T2 mapping values were measured. Results: There was a statistically significant change in T1 mapping values. Before HSCT, mean T1 mapping was 1226.13 ± 39.74 ms, and after HSCT, it was 1248.70 ± 41.07 ms (p = 0.01). The other parameters did not differ significantly. Conclusions: Increases in T1 mapping values following HSCT can show the progress of diffuse myocardial fibrosis and may reflect subclinical injury. T2 mapping values remain the same and do not show edema and active inflammation processes at 12 months after HSCT. Full article

This article aims to present cryoanalgesia as an inventive strategy for pain alleviation among pediatric patients. It underlines the tremendous need to align pain management with the principles of the enhanced recovery after surgery (ERAS) approach. The aim of the study was to review the patient outcomes of nerve cryoanalgesia during surgery reported with regard to ERAS in the literature. The literature search was performed using PubMed and Embase to identify articles on the use of cryoanalgesia in children. It excluded editorials, reviews, meta-analyses, and non-English articles. The analysis focused on the study methods, data analysis, patient selection, and patient follow-up. This review includes a total of 25 articles. Three of the articles report the results of cryoanalgesia implemented in ERAS protocol in children. The research outcome indicates shortened hospital stay, potential reduction in opioid dosage, and significant progress in physical rehabilitation. This paper also describes the first intraoperative utilization of intercostal nerve cryoanalgesia during the Nuss procedure in Poland, highlighting its effectiveness in pain management. Adding the cryoanalgesia procedure to multimodal analgesia protocol may facilitate the implementation of the ERAS protocol in pediatric patients. Full article