Search Results (27,216)

Background: The clinical relevance of clearly defined pretherapeutic basal calcitonin (bCt) cut-offs for predicting lymph node metastases (LNMs) and long-term outcomes (LOs) has so far not been tested in a large cohort of patients with medullary thyroid cancer included in a Ct screening program during the initial diagnostic workup of thyroid nodules. Material and Methods: Female (f) patients with a bCt level of ≤23 pg/mL and male (m) patients with a level of ≤43 pg/mL were assigned to Group 1 (minimal oncologic risk), patients with a bCt between 24 and 84 pg/mL (f) and 44–99 pg/mL (m) to Group 2 (low oncologic risk), and those with a bCt of ≥85 pg/mL (f) and ≥100 pg/mL (m) to Group 3 (high oncologic risk). All patients underwent surgery applying a uniform surgical protocol. The median follow-up was 100 months. Results: The study included 306 patients. In 3/115 (2.6%) patients in Group 1 and in 3/50 (6.0%) in Group 2, LNM in the central but not lateral neck and no distant metastases (DMet) were documented. In both groups, the biochemical long-term cure rate was 95.7% and the disease-specific-survival (DSS) rate was 100% at 10, 15 and 20 years. Lateral LNM and DMet were diagnosed only in Group 3. The bCt levels of N0 and N1 patients showed broadly overlapping ranges, thus impeding the differentiation between those patients through bCt. Both the cure rate and DSS were significantly worse in Group 3. The overall biochemical long-term cure rate was 78.2%. Conclusions: Within a Ct screening program, grouping patients upon pretherapeutic bCt provides a simple risk classification system for indicating surgery, predicting LN involvement, and LOs. Full article

Objective: This study investigated the influence of the vacuum phenomenon (VP) on surgical outcomes in patients with lumbar spinal stenosis, comparing minimally invasive oblique lateral interbody fusion (MIS OLIF) and endoscopic decompression. Methods: A cohort of 110 patients diagnosed with lumbar spinal stenosis underwent either endoscopic decompression or MIS OLIF. Patients were classified into two groups based on the presence or absence of the VP on preoperative CT scans, non-VP (n = 42) and VP (n = 68). Radiologic and clinical outcomes, including back and leg pain assessed using the visual analogue scale (VAS), the Oswestry Disability Index (ODI), and the EuroQol-5 Dimension (Eq5D), were compared pre- and postoperatively over a 2-year follow-up period. Results: Preoperatively, the VP group exhibited significantly greater leg pain (p = 0.010), while no significant differences were observed in back pain or the ODI between the groups. In the non-VP group, decompression and fusion yielded similar outcomes, with decompression showing a better ODI score at 1 month (p = 0.018). In contrast, in the VP group, patients who underwent fusion showed significantly improved long-term leg pain outcomes compared to those who underwent decompression at both 1-year (p = 0.042) and 2-year (p = 0.017) follow-ups. Conclusions: The VP may indicate segmental instability and may play a role in the persistence of radiculopathy. Fusion surgery appears to offer better long-term relief in patients with the VP, whereas decompression alone is a viable option in non-VP cases. These findings suggest that the VP may be a useful factor in guiding surgical decision-making. Full article

Ischemia-modified albumin (IMA) has emerged as a pivotal biomarker for the early detection of ischemic conditions, particularly myocardial ischemia, where timely diagnosis is crucial for effective intervention. This review provides an overview of the analytical methods for assessment of IMA, including Albumin Cobalt Binding (ACB), Albumin Copper Binding (ACuB), Enzyme-Linked Immunosorbent Assay (ELISA), new techniques such as liquid crystal biosensors (LCB), quantum dot coupled X-ray fluorescence spectroscopy (Q-XRF), mass spectrometry (MS), and electron paramagnetic resonance (EPR) spectroscopy. Each method was thoroughly examined for its analytical performance in terms of sensitivity, specificity, and feasibility. The ACB assay is the most readily implementable method in clinical laboratories for its cost-effectiveness and operational simplicity. On the other hand, the ACuB assay exhibits enhanced sensitivity and specificity, driven by the superior binding affinity of copper to IMA. Furthermore, nanoparticle-enhanced immunoassays and liquid crystal biosensors, while more resource-intensive, significantly improve the analytical sensitivity and specificity of IMA detection, enabling earlier and more accurate identification of ischemic events. Additionally, different biological matrices, such as serum, saliva, and urine, were reviewed to identify the most suitable for accurate measurements in clinical application. Although serum was considered the gold standard, non-invasive matrices such as saliva and urine are becoming increasingly feasible due to advances in technology. This review underscores the role of IMA in clinical diagnostics and suggests how advanced analytical techniques have the potential to significantly enhance patient outcomes in ischemic disease management. Full article

Background: Neutralizing antibodies targeting the SARS-CoV-2 Spike protein reduce COVID-19-related risk of hospitalization, particularly in high-risk individuals. The COCOPREV-R study aimed to evaluate and compare clinical outcomes in high-risk SARS-CoV-2 patients treated with dual monoclonal antibody therapies and to identify associated virological factors. Methods: The COCOPREV-R study retrospectively collected real-world data from high-risk patients receiving Bamlanivimab/Etesevimab or Casirivimab/Imdevimab dual monoclonal antibody therapies (22 February 2021 to 15 June 2021). Results: The study included 1004 patients with COVID-19, of whom 691 received Bamlanivimab/Etesevimab and 313 received Casirivimab/Imdevimab. The alpha variant represented 90.1% of those for whom data were available. The risk of hospitalization within 30 days was lower with Bamlanivimab/Etesevimab (12.7%, CI 95% [9.9–16.3%]) compared to Casirivimab/Imdevimab (28.4%, CI 95% [22.7–35.1%) (p < 0.001). The 30-day mortality rates were comparable between both groups (p = 0.982). Analysis of SARS-CoV-2 PCR negativity showed no difference between the two treatment groups (95.2% [93.0–96.9%] and 93.5% [89.1–96.6%] until day 30, p = 0.851 for Bamlanivimab/Etesevimab and Casirivimab/Imdevimab, respectively). Among persistently positive samples with available sequencing results (n = 43), Spike protein changes occurred only in Bamlanivimab/Etesevimab (42.9%) vs. Casirivimab/Imdevimab (0.0%) groups. Q493R (25.0%) and E484K (12.5%) were the most common mutations selected by Bamlanivimab/Etesevimab in follow-up samples. Other factors (immunodepression, comorbidities, and age) did not appear to be associated with the occurrence of Spike protein mutations. Conclusions: A higher rate of hospitalization was seen with Casirivimab/Imdevimab (RONAPREVE^®) in comparison with Bamlanivimab/Etesevimab treatment, but with the emergence of Spike mutations only in the Bamlanivimab/Etesevimab group. Full article

Introduction: Regenerative medicine is revolutionizing oral and maxillofacial surgeries with stem cells, particularly mesenchymal stem cells, for tissue and bone regeneration. Despite promising in-vitro results, human trials are limited. A systematic review is needed to evaluate stem cell efficacy in maxillofacial issues, aiming to improve surgical outcomes and patient satisfaction. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines, this review included peer-reviewed articles (2013–2023) on stem cells in oral surgery, excluding non-English publications, abstracts, reviews, and opinion pieces. Searches were conducted in PubMed, Web of Science, OVID, Cochrane, Dentistry & Oral Sciences Source—Ebscohost, and Scopus. Two authors independently screened titles and abstracts, resolving disagreements by consensus. Full-text analysis involved extracting key data, verified by a secondary reviewer and additional quality checks. Results: From 3540 initial articles, 2528 were screened after removing duplicates, and 7 met the inclusion criteria after excluding irrelevant studies. Key themes included the safety and efficacy of stem cell therapy, and bone regeneration and quality. Studies predominantly used mesenchymal stem cells. Findings showed positive outcomes in clinical safety and effectiveness and significant potential for bone regeneration. Conclusions: This systematic review highlights the potential of stem cell therapies in maxillofacial applications, supporting their safety, efficacy, and bone regeneration capabilities. Further research is needed to standardize protocols and confirm long-term benefits. Full article

Background: The prognosis of patients diagnosed with locally advanced and metastatic gastric and esophago-gastric junction cancer is critical. The optimal choice of systemic therapy is essential to optimize survival outcomes. Methods: A comprehensive literature review via PubMed and analysis of major oncology congresses (European Society for Medical Oncology and American Society of Clinical Oncology websites) were conducted to ascertain the current status and latest developments in the systemic treatment of patients with localized or advanced gastric and esophago-gastric junction adenocarcinoma. Results: While neoadjuvant and perioperative chemotherapy for localized tumor stages is the preferred approach in the Western Hemisphere, adjuvant chemotherapy remains the preferred course of action in East Asia. The administration of chemotherapy, typically in the form of combinations comprising platinum and fluoropyrimidine compounds in combination with docetaxel, represents a standard of care. Investigations are underway into the potential of immunotherapy and other biologically targeted agents in the perioperative setting. To select the most appropriate therapy for advanced gastric cancer, including adenocarcinoma of the esophago-gastric junction, it is essential to determine biomarkers such as HER2 expression, PD-L1 combined positive score (CPS) (combined positive score), Claudin 18.2, and microsatellite instability (MSI). In the present clinical context, the standard first-line therapy is a combination of fluoropyrimidine and a platinum derivative. The selection of chemotherapy in combination with antibodies is contingent upon the specific biomarker under consideration. Conclusions: This article reviews the current state of the art based on recent clinical trial results and provides an outlook on the future of systemic therapy. Full article

Background/Objectives: Biological products are emerging as therapeutic management options for intervertebral disc (IVD) degenerative affections and lower back pain. Autologous and allogeneic cell therapy protocols have been clinically implemented for IVD repair. Therein, several manufacturing process design considerations were shown to significantly influence clinical outcomes. The primary objective of this study was to preclinically qualify (chondrogenic potential, safety, resistance to hypoxic and inflammatory stimuli) cryopreserved primary progenitor cells (clinical grade FE002-Disc cells) as a potential cell source in IVD repair/regeneration. The secondary objective of this study was to assess the cell source’s delivery potential as cell spheroids (optimization of culture conditions, potential storage solutions). Methods/Results: Safety (soft agar transformation, β-galactosidase, telomerase activity) and functionality-related assays (hypoxic and inflammatory challenge) confirmed that the investigated cellular active substance was highly sustainable in defined cell banking workflows, despite possessing a finite in vitro lifespan. Functionality-related assays confirmed that the retained manufacturing process yielded strong collagen II and glycosaminoglycan (GAG) synthesis in the spheroids in 3-week chondrogenic induction. Then, the impacts of various process parameters (induction medium composition, hypoxic incubation, terminal spheroid lyophilization) were studied to gain insights on their criticality. Finally, an optimal set of technical specifications (use of 10 nM dexamethasone for chondrogenic induction, 2% O₂ incubation of spheroids) was set forth, based on specific fine tuning of finished product critical functional attributes. Conclusions: Generally, this study qualified the considered FE002-Disc progenitor cell source for further preclinical investigation based on safety, quality, and functionality datasets. The novelty and significance of this study resided in the establishment of defined processes for preparing fresh, off-the-freezer, or off-the-shelf IVD spheroids using a preclinically qualified allogeneic human cell source. Overall, this study underscored the importance of using robust product components and optimal manufacturing process variants for maximization of finished cell-based formulation quality attributes. Full article

OnabotulinumtoxinA (onabotA) is approved in the US for 12 therapeutic indications. Real-world data on onabotA multi-indication use are limited, often leading to delayed or reduced treatment. This study provides real-world evidence on the safety of onabotA when treating multiple indications concomitantly. SYNCHRONIZE was a multicenter, retrospective, chart-review study evaluating onabotA’s safety for adults treated for ≥2 therapeutic indications within a 3-month period. The primary outcome was treatment-emergent adverse events (TEAEs) within 6 months post-treatment. A total of 279 patients were included. The most common concomitant indications treated were cervical dystonia and chronic migraine (43.4%). The average 3-month cumulative dose for multiple indications was 282.2 U. The treatment interval for multiple indications was ≤24 h for most patients (62.4%). Overall, 28.7% of patients reported ≥1 TEAE with no apparent trends in TEAEs and dose interval or cumulative dose. Reported TEAEs included UTI (5.7%), neck pain (5.0%), and headache (4.3%). No patient had a lack of effect according to clinical objective measurements. SYNCHRONIZE described the real-world safety of onabotA for patients treated concomitantly for ≥2 indications within a 3-month period. TEAEs were generally consistent with the known safety profiles of individual indications. No new safety signals were identified). Full article

Introduction: Optical Coherence Tomography (OCT) has emerged as an important imaging modality in non-invasive diagnosis for oral cancer and can provide real-time visualisation of tissue morphology with the required high resolution. This systematic review aims to assess the diagnostic accuracy of OCT in the detection of oral cancers, and to explore the potential integration of OCT with artificial intelligence (AI) and other imaging techniques to enhance diagnostic precision and clinical outcomes in oral healthcare. Methods: A systematic literature search was conducted across PubMed, Embase, Scopus, Google Scholar, Cochrane Central Register, and Web of Science from inception until August 2024. Studies were included if they employed OCT for oral cancer detection, reported diagnostic outcomes, such as sensitivity and specificity, and were conducted on human subjects. Data extraction and quality assessment were performed independently by two reviewers. The synthesis highlights advancements in OCT technology, including AI-enhanced interpretations. Results: A total of 9 studies met the inclusion criteria, encompassing a total of 860 events (cancer detections). The studies spanned from 2008 to 2022 and utilised various OCT techniques, including clinician-based, algorithm-based, and AI-driven interpretations. The findings indicate OCT’s high diagnostic accuracy, with sensitivity ranging from 75% to 100% and specificity from 71% to 100%. AI-augmented OCT interpretations demonstrated the highest accuracy, emphasising OCT’s potential in early cancer detection and precision in guiding surgical interventions. Conclusions: OCT could play a very prominent role as a new diagnostic tool for oral cancer, with very high sensitivity and specificity. Future research pointed towards integrating OCT with other imaging methods and AI systems in providing better accuracy of diagnoses, plus more clinical usability. Further development and validation with large-scale multicentre trials is imperative for the realisation of this potential in changing the way we practice oral healthcare. Full article

Background/Objectives: Locating the mandibular foramen (MF) through imaging is clinically important for inferior alveolar nerve (IAN) anesthesia and mandibular ramus osteotomies. Although cone-beam computed tomography (CBCT) is superior in imaging the mandible, an orthopantomogram (OPG) is preferred for its ease of use and availability. Therefore, the present study aimed to evaluate the accuracy of digital OPG in localizing the MF, in a subset of the Middle Eastern population. Methods: Radiographic images (OPG and CBCT) of selected patients (adults, dentulous and no mandibular abnormalities) were used to locate the MF through digital measurements (mm) of the anteroposterior distance from the anterior border of the ramus (MF-AP) and the superoinferior position from the mandibular occlusal plane (MF-SI). Measurements were statistically compared between OPG and CBCT for accuracy. Differences in measurements between OPG and CBCT were compared against the anatomic location (right/left), age and biological sex, assuming a p-value < 0.05 as significant. Results: A total of 204 radiographic records (males: 100/females: 104/mean age: 34.65 ± 11.55 years) were evaluated. The measurements for the MF were MF-AP-OPG (right: 13.53 ± 2.44/left: 13.19 ± 2.25), MF-AP-CBCT (right: 13.61 ± 2.39/left: 13.36 ± 2.19), MF-SI-OPG (right: 5.25 ± 1.71/left: 5.41 ± 1.65) and MF-SI-CBCT (right: 5.59 ± 1.66/left: 5.52 ± 1.61). Measurements between OPG and CBCT were not significantly different, except for MF-SI (right) (p = 0.042). While the overall difference between OPG and CBCT (MF-AP/MF-SI) measurements showed a significant association (p < 0.01) with the anatomic location (right/left), a significant association (p < 0.05) with biological sex was observed only for MF-AP. Conclusions: Based on this study’s outcomes, digital OPG is an accurate modality to locate the MF based on anteroposterior (MF-AP) and superoinferior (MF-SI) measurements. This would be clinically beneficial for dental and oral surgeons to achieve the optimum IAN block anesthesia based on preoperative panoramic radiographs. Similarly, it would assist maxillofacial surgeons in planning mandibular orthognathic surgeries and ramus osteotomies without complications. Full article

Multiple myeloma (MM) is a hematological malignancy and poses significant therapeutic challenges. This review synthesizes evidence from pivotal clinical trials to guide induction treatment for transplant-eligible (TE), newly diagnosed MM (NDMM) patients. Emphasizing the evolution from three-drug to four-drug induction therapies, we highlight the integration of monoclonal antibodies, particularly CD38 recombinant monoclonal antibody agents, into treatment regimens. This analysis includes a comprehensive literature review of research from major databases and conferences conducted between 2010 and 2023, culminating in the detailed evaluation of 47 studies. The findings underscore the superiority of quadruple regimens in TE NDMM, notably those incorporating daratumumab, in achieving superior responses including progression-free survival (PFS), minimal residual disease (MRD) negativity, objective response rate (ORR), and overall survival (OS) when compared to triple-drug regimens. As treatment regimens evolve with additional agents, the improved outcomes with treatment-related adverse events should be carefully balanced. This review advocates for a paradigm shift towards quadruple induction therapies for TE NDMM, offers a detailed insight into the current landscape of MM treatment, and reinforces a new standard of care. Full article

Background/objectives: The efficacy of lung metastasectomy in patients with urothelial carcinoma remains inconclusive, as there is only limited evidence from small studies. In this study, we aimed to assess the prognostic outcomes of excising pulmonary metastases from urothelial carcinoma. Methods: In this study, we utilized data from the Metastatic Lung Tumor Study Group of Japan database, a multi-institutional prospective database of pulmonary metastasectomies. We examined the data of patients who had undergone pulmonary metastasectomy for urothelial carcinoma between 1985 and 2021. Exclusion criteria included insufficient clinical information and follow-up of <3 months. Results: The study cohort comprised 100 patients (63 bladder cancer, 37 renal pelvic and ureteral cancer), with a median follow-up of 34 months. There were 70 male and 30 female patients of average age 66.5 ± 10.4 years at lung metastasectomy. The median interval from treatment of the primary lesion to metastasectomy was 19 months and the maximum tumor diameter was 21 ± 15 mm. Three- and five-year overall survival rates were 69% and 59%, respectively. Three- and five-year disease-free survival rates were 56% and 46%, respectively. Multivariate analysis identified larger tumor diameter (hazard ratio: 1.62, 95% confidence interval: 1.21–2.17) and distant metastases at the time of treatment of the primary cancer (hazard ratio: 4.23; 95% confidence interval: 1.54–11.6) as significant adverse prognostic factors for overall survival. Conclusions: To our knowledge, this is the largest published case series of pulmonary resection for metastatic urothelial carcinoma, providing benchmark data for the assessment of long-term outcomes of this rare entity. Full article

Patients affected by familial hypercholesterolemia possess elevated low-density lipoprotein cholesterol and therefore have greater risk for cardiovascular disease. About 90% of familial hypercholesterolemia cases are associated with aberrant LDLR. Over 3500 LDLR variants have been identified, 15% of which are considered “pathogenic.” Given the genetic diversity of LDLR variants, specific variants rarely receive attention. However, investigators have proposed the critical evaluation of individual variants as a method to clarify knowledge and to resolve discrepancies in the literature. This article reviews p.(Val429Met) (rs28942078) in the areas of pathology, epidemiology, lipid-lowering therapy, and genetic testing. The p.(Val429Met) variant is associated with a missense point substitution in exon 9 of chromosome 19. Biochemical studies have found severely reduced low-density lipoprotein receptor protein in autologous and heterologous expression systems. Additionally, there are inconsistencies regarding the functional classification of p.(Val429Met). Considered to be of European origin, p.(Val429Met) is found in extant populations due to founder effects. Evidence from clinical trials have also demonstrated variable responses to newer lipid-lowering therapies in patients with a p.(Val429Met) variant. Proper clinical detection and adequate genetic testing have been shown to greatly improve outcomes. Future research may be aimed at resolving discrepancies to better comprehend the implications of familial hypercholesterolemia. Full article

Objective: To assess the survival outcomes of patients diagnosed with muscle-invasive bladder cancer (MIBC) who are not candidates for curative treatment and to identify the factors influencing these outcomes. Methods: We conducted an analysis of patients diagnosed with MIBC who were either unable or unwilling to undergo curative therapy. We evaluated overall survival (OS) and cancer-specific survival (CSS) and examined their associations with various clinical variables. Additionally, we assessed emergency department visits and palliative procedures. Results: The study included 142 patients with a median age of 79.4 years and a Charlson Comorbidity Index of 9.8. At diagnosis, 59.2% of the patients had localized disease, 23.2% had metastatic disease, and 49.3% presented with hydronephrosis. Curative treatment was excluded due to comorbidities in 40.1% of cases and advanced disease stage in 36.6%. The 1-year and 2-year OS rates were 42.8% and 23.6%, respectively, with a median survival of 10.6 months. The 1-year and 2-year CSS rates were 49.6% and 30.2%, respectively, with a median survival of 11.9 months. Worse survival outcomes were associated with advanced disease stage and the presence of hydronephrosis. Patients excluded from curative treatment solely due to age had a relatively better prognosis. On average, patients visited the emergency department three times: 19% underwent palliative transurethral resection of the bladder tumor, 14.8% received radiotherapy to control hematuria, and nephrostomy tubes were placed in 26.1% of cases. Conclusions: Patients with MIBC who are unable or unwilling to undergo curative treatment have a median overall survival of less than one year, with worse outcomes observed in those with advanced disease stage and hydronephrosis. Full article

Background: For patients with head and neck squamous cell carcinoma (HNSCC), after a single or multi-modality treatment, a specific follow-up strategy is needed, but there is no agreement between the main international societies on the proper methods and timing of follow-up. Methods: We performed a descriptive review to evaluate the available data and compare the main guidelines, giving some practical guidance to perform effective personalized follow-up strategies. Results and Conclusions: While clinical and endoscopic follow-up alone seems to be appropriate for early-stage HNSCCs, the addition of close radiologic follow-up in locally advanced HNSCCs is still debated, as there are no data indicating that an earlier detection of recurrence correlates with increased survival, while it is mandatory in the first three-six months to define the response to treatment. For patients who have undergone conservative surgery or have major pathological risk factors, the incidence of locoregional recurrence is higher, and locoregional radiologic follow-up (magnetic resonance imaging is preferred to computed tomography) should be considered. Positron emission tomography may be useful in cases of suspected locoregional persistence of disease, differentiating it from post-irradiation outcomes. Distant radiological follow-up can be considered in the detection of the second primary in cases of specific risk factors and for virus-related tumors. For the latter, the use of circulating DNA should always be considered. A brain scan is not recommended without specific symptoms. For all patients who do not fall into the above categories, clinical and endoscopic follow-up should be proposed, reserving radiological investigations only at the onset of symptoms. Full article