Abstract: The link between cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated fatty liver disease (MAFLD)/metabolic dys-function-associated steatotic liver disease (MASLD) is well-established at both epidemi-ological and pathophysiological level. Among the common pathophysiological mechanisms involved in the development and progression of both diseases, oxidative stress and inflammation, insulin resistance, lipid metabolism deterioration, gut dysbiosis along with genetic factors have been rec-ognized to play a pivotal role. Pharmacologic interventions with drugs targeting common modifiable cardiometabolic risk factors, such as T2DM, dyslipidemia, and hypertension is a reasonable strategy to prevent CVD development and progression of MASLD. Recently, a novel drug for MASH, resmetirom, has shown positive effects regarding CVD risk, opening new opportunities for the therapeutic approach of NAFLD/MAFLD/MASLD and CVD. This review provides current knowledge on the epidemiologic association of NAFLD/MAFLD/MASLD to CVD morbidity and mortality and enlightens the possible underlying pathophysiologic mechanisms linking NAFLD/MAFLD/MASLD with CVD. It also highlights potential common therapeutic interventions with cardiometabolic drugs such as anti-hypertensive drugs, hypolipidemic agents, glucose-lowering medications, salicylic acid and the thyroid hormone receptor-beta agonist that may improve outcomes of NAFLD/MAFLD/MASLD.

Abstract: Objectives This study aimed to evaluate the outcomes of the Subcrestally Placed Implants (SPI) with Internal Platform Switching (IPS) design in single molar replacements utilizing the matching abutment technique. The investigation focused on achieving biological stability and esthetics while proposing a schematic model to seek the relationship between the biological stability of peri-implant soft tissue and crestal bone. Materials and Methods Twenty cases of SPI with IPS design were evaluated. Panoramic radiographs were employed to assess changes in crestal bone levels at the mesial and distal sides over an average follow-up period of 3.4 years, providing a practical method for routine monitoring. CBCT scans, acquired at least one year after surgery, were comprehensively analyzed to determine the dimensions of peri-implant soft tissue in a three-dimensional context. Parameters assessed included: Placement depth (PD), both central (cPD) and peripheral (pPD). Soft tissue thickness (STT), both central (cSTT) and peripheral (pSTT). Transitional Zone (TZ) length at the mesial, distal, buccal, and lingual aspects. To evaluate the health of peri-implant soft tissue, the following clinical assessments were performed: IPPP (Implant Paper Point Probe) Bleeding on Probing (BOP) Visual Assessment for redness and swelling Results 1. Panoramic Analysis Panoramic radiographs revealed stable crestal bone levels with minimal changes, with mean pPD change observed to be less than 0.1 mm over an average follow-up period of 3.3 years. 2. CBCT Analysis o The average central placement depth (cPD) was 1.4 mm, and the peripheral placement depth (pPD) was 2.7 mm. o The average central soft tissue thickness (cSTT) was 0.3 mm, and the peripheral soft tissue thickness (pSTT) was 0.6 mm. o The average Transitional Zone (TZ) length was 4.3 mm. 3. Clinical Observations o Depth of Probing: Probing depths were consistently less than 1 mm in all cases, demonstrating minimal pocket formation and stable peri-implant conditions. o Bleeding on Probing (BOP): No bleeding was observed in any case, suggesting an absence of inflammation around the implants. o Visual Signs of Inflammation: No swelling, redness, or other visual indicators of inflammation were detected, reflecting healthy peri-implant soft tissue in all cases. Conclusions The findings of this study demonstrated that subcrestally placed implants (SPI) with an internal platform switching (IPS) design, utilizing the matching abutment technique, provide stable outcomes, particularly in terms of crestal bone levels and peri-implant soft tissue dimensions. This stability is likely attributed to the biological and structural integrity at the soft tissue-implant restoration interface (Transitional Zone). The study investigated the three-dimensional topography of peri-implant soft tissue, emphasizing its relationship with implant restoration, crestal bone changes, and clinical outcomes. Further histological research is necessary to validate the unique characteristics and mechanical properties of these zones, offering deeper insights into their contribution to long-term implant success and enhanced esthetics.

Abstract:

Background/Objectives: Rifaximin is commonly used for patients with hepatic encephalopathy (HE); however, there is little data on the effects of its long-term (>1 year) administration in Jap-anese patients with cirrhosis. Therefore, we examined the effects and safety of three-year rifaxi-min treatment on HE in Japan. Methods: A total of 190 patients with cirrhosis who were contin-uously administered rifaximin for more than one year developed overt or covert HE, which was diagnosed by a physician. Laboratory data were collected at baseline, 3, 6, 12, 18, 24, 30, and 36 months following rifaximin administration. We examined the cumulative OHE incidences, overall survival rates, and hepatic functional reserves following rifaximin treatment. The occur-rence of adverse events was also assessed. Results: Ammonia levels improved significantly after 3 months of rifaximin administration, which continued for three years. Serum albumin and pro-thrombin activity also significantly improved after three years of rifaximin administration. Cumulative overt HE incidences were 12.1%, 19.7%, and 24.9% at 1, 2, and 3 years, respectively. The survival rates following rifaximin treatment were 100%, 88.9%, and 77.8% at 1, 2, and 3 years, respectively. In contrast, renal function and electrolytes did not change following rifaximin ad-ministration. Only three (1.6%) patients discontinued RFX therapy because of severe diarrhea after a year of RFX administration. No other serious adverse events were observed. Conclusion: Long-term rifaximin treatment (three years) is effective and safe for patients with HE and im-proves the hepatic function reserve and overall survival.

Abstract: Background: During the last few years, significant pathophysiological differences between heart failure (HF) patients with “normal” ejection fraction (EF) (50% to 64%) and those with supra-normal EF (≥65%) have been highlighted. However, these distinct EF phenotypes have been poorly investigated in elderly patients aged ≥70 yrs. Methods: All patients aged ≥70 yrs discharged from our Institution with a first diagnosis of HF with preserved EF (HFpEF) be-tween January 2020 and March 2021 entered the study. All patients underwent clinical evalua-tion, blood tests and transthoracic echocardiography. The primary endpoint was “all-cause mortality”, while the secondary one was the composite of “all-cause mortality or rehospitali-zation for all causes” over a mid-term follow-up. Results: A total of 200 HFpEF patients (86.4±6.6 yrs, 70% females) were retrospectively evaluated. The “normal” EF group (n=99) and the “supra-normal” EF one (n=101) were separately analyzed. Compared to patients with “normal” EF, those with “supra-normal” EF were older, with greater comorbidity burden and moderate-to-severe frailty status. During a mean follow-up of 3.6±0.3 yrs, 79 patients died and 73 were re-hospitalized. On multivariate Cox regression analysis, age (HR 1.09, 95% CI 1.03-1.16, p = 0.002), EF (HR 1.08, 95% CI 1.03-1.14, p = 0.004), tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (sPAP) ratio (HR 0.14, 95% CI 0.03-0.61, p = 0.009) and infectious disease (HR 7.23, 95% CI 2.41-21.6, p < 0.001) were independently as-sociated with all-cause mortality in the whole study population. EF (HR 1.04, 95% CI 1.01-1.07, p = 0.02) also predicted the secondary endpoint. EF ≥65% was the best cut-off to predict both endpoints. Conclusions: “Supra-normal” EF (≥65%) at hospital admission is independently associated with all-cause mortality and rehospitalization for all causes in elderly HFpEF pa-tients over a mid-term follow-up.

Abstract:

Alzheimer's disease (AD) is a neurodegenerative condition that has no definitive treatment and its early diagnosis can help to prevent or slow down its progress. Neuroimaging in particular, structural magnetic resonance imaging (sMRI) and the progress of artificial intelligence (AI) have significant attention in AD detection. In this study, 398 participants were used from the ADNI and OASIS global database of sMRI including 98 individuals with AD, 102 with early mild cognitive impairment (EMCI), 98 with late mild cognitive impairment (LMCI), and 100 normal controls (NC). The proposed model achieved high area under the curve (AUC) values and an accuracy of 99.7%, which is very remarkable for all four classes: NC vs. AD: AUC = [0.985], EMCI vs. NC: AUC = [0.961], LMCI vs. NC: AUC = [0.951], LMCI vs. AD: AUC = [0.989], and EMCI vs. LMCI: AUC = [1.000]. The results reveal that this model incorporates DenseNet169, transfer learning, and class decomposition to classify AD stages, particularly in differentiating EMCI from LMCI. Overall, this model performs well with high accuracy and area under the curve for AD diagnostics at early stages.

Abstract: Advancements in omics technologies have promoted the development of precision oncology. Lineage plasticity, a hallmark of cancer, incorporates molecular and histological aspects. Histological differentiation of adenocarcinoma, neuroendocrine, and squamous characteristics occurs in different anatomic locations. Lung cancer, which is highly heterogeneous, encompasses these differentiations, and therefore serves as a model for exploration. Data-driven understanding is critical in cancer differentiation research, with the two major differentiation pathways, squamous and neuroendocrine, supported by omics data. Here, genetic and non-genetic profiles are reviewed based on patient datasets, and shareable molecular features are described. This paper mainly discusses machine learning approaches to feature selection, where network modeling is effective for designing programmable differentiation. All methods are presented within the context of cancer lineage plasticity along with examples and hypotheses. It emphasizes that selected patient datasets combined with methods will ultimately lead to actionable cancer lineage. Chances for clinical translation are in the spotlight, including biomarkers, molecular subtypes, and targeted therapies.

Abstract:

Objective. The strategy of active surveillance for papillary thyroid microcarcinoma (PTMC) is currently becoming more popular in the global medical community. The pivotal criterion for choosing the active surveillance strategy is the absence of any signs of lymphogenic or distant metastases. In the present work, we assessed the diagnostic accuracy of molecular genetic markers in predicting the metastatic potential in patients with PTMC. Methods. The expression level of 33 molecular genetic markers in cytology samples from 92 patients with PTMC with the known histological diagnosis, including 32 with metastases to regional cervical lymph nodes, was assessed. The list included 22 genes and 11 microRNAs. The presence of the somatic BRAF V600E mutation was investigated separately. Results. In patients with metastatic PTMC, the HMGA2 gene, the TIMP1 gene, and the FN1 gene were more active, and microRNA-146b expression was upregulated. Downregulated expression of microRNA-7 and -148b was also detected in metastatic tumors, which is indicative of their tumor suppressor role. Metastatic tumors were characterized by on average 11-fold lower activity of DIO1, eightfold lower expression of the TFF3 gene, fourfold lower expression of TPO. All the markers, except for BRAF mutation, have high sensitivity (84.5–90.6%) for detecting metastatic PTMC but low specificity (~ 50%). Conclusions. Application of molecular markers for predicting lymphogenic metastatic spread in patients with PTMC can possibly supplement the existing risk grading systems. These studies are relatively simple to conduct and available as early as at the preoperative stage.

Abstract:

Introduction: The etiology of lumbar spine revision surgery is multifactorial, involving mechanical, biological, and clinical factors that challenge sustained spinal stability. Comparative analysis reveals significantly higher complication rates, prolonged hospital stays, and increased costs for revision surgeries compared to primary fusions despite low mortality rates. Leveraging a comprehensive dataset of 456,750 patients, this study identifies predictors of revision surgery and provides actionable insights to enhance patient outcomes and optimize healthcare resource allocation. Methods: A total of 456,750 patients registered in the National Inpatient Sample (NIS) database from 2016 to 2019 were identified as having undergone single-level lumbar fusion surgery (primary fusion: 99.5%; revision fusion: 0.5%). Multivariable logistic regression models adjusted for patient demographics, clinical comorbidities, and hospital characteristics were constructed to evaluate clinical outcomes and postoperative complications. Results: Patients undergoing revision lumbar fusion surgery were significantly younger compared to those experiencing primary fusion procedures (53.92 ± 20.65 vs. 61.87 ± 12.32 years, P < 0.001); among the entire cohort, 56.4% were women. Compared with patients undergoing primary lumbar fusion, those undergoing revision fusion surgery were significantly more likely to experience surgical site infections (odds ratio [OR] 27.10; 95% confidence interval [95% CI] 17.12–42.90; P < 0.001), urinary tract infections (OR 2.15; 95% CI 1.39–3.33; P < 0.001), and prolonged length of stay (OR 1.53; 95% CI 1.24–1.89; P < 0.001). Revision surgery patients had significantly lower odds of incurring high-end hospital charges (OR 0.65; 95% CI 0.51–0.83; P < 0.001). Other complications, including respiratory complications, dural tears, thromboembolic events, and acute renal failure, showed no statistically significant differences between the two groups. In-hospital mortality rates were low and did not differ significantly between groups (revision: 0.2% vs. primary: 0.1%, OR 3.29; 95% CI 0.45–23.84; P = 0.23). Conclusions: Patients undergoing revision lumbar fusion surgeries face significantly higher risks of surgical site infections, urinary tract infections, and prolonged hospital stays compared to primary fusion procedures. These findings highlight the need for targeted interventions to improve perioperative management and reduce complications in revision lumbar fusion surgery.

Abstract: Background/Objectives: Laryngeal squamous cell carcinoma (LSCC) is a common malignancy with unsatisfactory survival rates, highlighting the need for reliable biomarkers to improve diagnosis and prognosis. Growth differentiation factor 15 (GDF15), a protein implicated in various cancers, has not been thoroughly investigated in LSCC. This study aimed to evaluate the significance of GDF15 expression in LSCC and its potential clinical implications. Methods: We analyzed archival tissue samples from 65 LSCC patients using immunohistochemistry and evaluated GDF15 expression profiles from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Statistical analyses included Kaplan-Meier survival analysis and Cox proportional hazards regression to assess the correlation between GDF15 expression, clinicopathological variables, and survival outcomes. Results: GDF15 expression showed no significant difference between tumor and adjacent normal tissues. However, in the tissue macroarray (TMA) cohort, high GDF15 expression was significantly associated with lower TNM stage and less advanced pT status. Kaplan-Meier analysis revealed that high GDF15 expression correlated with poorer overall survival in the TMA cohort but not in the TCGA or GEO datasets. Multivariable analysis identified GDF15 as an independent prognostic factor for disease-free survival in LSCC. Conclusions: Our findings suggest that GDF15 may serve as a prognostic biomarker in LSCC, particularly in early-stage disease. Further research is warranted to validate these results and explore GDF15's potential as a therapeutic target, contributing to improved patient management.

Abstract: The inherited genetic disorder β-thalassemia affects the hematopoietic system and is caused by low production or absence of adult hemoglobin (HbA). Ineffective erythropoiesis is the hallmark of β-thalassemia pathophysiology and is characterized by an erythropoietin-driven substantial increase in erythroblast proliferation, coupled with an increase in late-stage precursor apoptosis, which results in low levels of circulating mature red blood cells (RBCs) and chronic anemia. Mitochondrial dysfunction commonly occurs in these cells because of the increased demand for energy production and the need to manage abnormal hemoglobin chain synthesis. Moreover, several studies have highlighted the importance of gradual mitochondrial clearance for mature erythroid cell production. In this review, we presented the available information on the role of mitochondria in vital cellular processes, which makes them promising pharmacological targets for maintaining the health and function of RBCs.