Search Results (3,384)

Background: Locally advanced prostate cancer (PCa) is commonly treated with multimodal therapy; however, long-term outcomes of surgery alone are poorly defined. We investigated the potential and limitations of robot-assisted radical prostatectomy (RARP) as primary treatment without perioperative systemic therapy in patients with locally advanced PCa. Methods: We retrospectively analyzed 258 patients who underwent RARP with extended pelvic lymph node dissection between 2012 and 2022 with locally advanced PCa, defined as present if at least one of the following was met: clinical stage cT3b–T4; primary Gleason pattern 5; >4 biopsy cores with Grade Group 4 or 5; or more than one NCCN high-risk characteristic. Patients who received neoadjuvant or adjuvant therapy were excluded. Endpoints included biochemical recurrence-free survival, metastasis-free survival, cancer-specific survival, and predictors of persistent PSA. Results: Median follow-up was 60.6 months. Pathological stage ≥ pT3a occurred in 63.6% and nodal involvement (pN1) in 27.1%. Five-year BRFS, MFS, and CSS were 36.6%, 88.9%, and 98.3%, respectively. Persistent PSA occurred in 21.3%. Preoperative predictors included PSA > 40 ng/mL, clinical stage ≥ cT3a, and >4 biopsy cores with a Gleason score of 8–10; patients with ≥2 features had significantly poorer BRFS and MFS. Postoperative predictors of recurrence were pathological stage, lymphovascular invasion, and nodal involvement. Conclusions: RARP alone provided durable long-term cancer control in selected men with locally advanced PCa, whereas patients with multiple adverse features were unlikely to be cured with surgery alone. Careful risk stratification may identify candidates for surgical monotherapy and help avoid overtreatment, while others may benefit from multimodal therapy. Full article

Herpes simplex virus type 1 (HSV-1) is a continuous health challenge, and current antiviral treatments cannot cure the virus. As life expectancy continues to increase worldwide, HSV-1 should remain a focus to minimize its associated health complications within the aging population. While often asymptomatic, HSV-1 causes oral and cutaneous lesions and establishes latency with periodic reactivation. Antivirals reduce symptoms but do not eradicate the virus. Emerging evidence links HSV-1 to Alzheimer’s disease (AD) via chronic neuroinflammation, amyloid-beta and tau accumulation, oxidative stress, and synaptic dysfunction, with viral proteins detected in AD-affected brain regions. This review assesses the current evidence for HSV-1 in dementia pathogenesis, examines antiviral strategies as potential neuroprotective interventions, and outlines the experimental models required to establish causality. Full article

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL) worldwide. Currently, approximately sixty percent of patients are cured with R-CHOP as frontline treatment, while the remaining patients experience primary refractory or relapsed (R/R) disease. Recently, the introduction of Pola-R-CHP as front-line therapy has represented a major advance in the management of DLBCL, resulting in improved outcomes. Prognosis of R/R DLBCL patients is poor, particularly for those eligible neither for chimeric antigen receptor (CAR) T-cell therapy nor autologous stem cell transplantation (ASCT), representing a significant unmet clinical need. The advent of bispecific monoclonal antibodies (BsAbs), such as bispecific T-cell engagers (BiTEs), dual affinity retargeting (DART) molecules and IgG-like bispecific antibodies, offers a novel promising therapeutic approach in the treatment of DLBCL, both as frontline treatment and in the R/R setting. BsAbs simultaneously engage two different antigens, a tumor-associated antigen and an immune cell antigen, redirecting T-cells against malignant cells and enhancing the immune response. Most BsAbs developed for the treatment of NHLs engage T-cells via CD3 and malignant B-cells via CD20, a surface antigen expressed on most lymphomatous cells. Engagement of malignant B-cells by BsAbs activates T-cells, leading to the release of multiple cytokines and potentially to two characteristic adverse events: cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The most extensively studied BsAbs, in both the frontline and relapsed/refractory (R/R) settings, include epcoritamab, glofitamab, mosunetuzumab, and odronextamab. Epcoritamab and glofitamab have received FDA and EMA approval for R/R DLBCL after two or more systemic line of therapies. EMA has also approved glofitamab in combination with gemcitabine and oxaliplatin (GemOx) for patients with R/R DLBCL ineligible for ASCT, whereas this indication has not been approved by FDA. Odronextamab is approved by EMA for R/R DLBCL and FL in patients who have received at least two prior lines of therapy, but it has not been approved by FDA. Mosunetuzumab is approved by both agencies—but only for R/R follicular lymphoma (FL). BsAbs represent a breakthrough therapy in the treatment of DLBCL, especially in R/R diseases. The purpose of this article is to review the landscape of BsAbs in DLBCL. Full article

Background/Objectives: Testicular germ cell tumours (GCT) have high cure rates, especially in early stages. MicroRNA-371a-3p (M371) has recently emerged as a highly sensitive biomarker for malignant GCTs, except teratoma. This study aimed to evaluate the diagnostic performance of M371-test in a real-life clinical setting, compared to conventional markers alpha-fetoprotein (AFP), lactate-dehydrogenase (LDH), and beta-human chorionic gonadotropin (β-HCG) in patients with suspected GCT. Methods: The study, approved by the Ethic-Committee of the Provincial Hospital of Bolzano (N.97-2021), included 91 M371-tests, performed from March 2021 to May 2025. A total of 75 patients had suspected GCT; 19 healthy males served as control. Serum levels of M371, AFP, LDH, and β-HCG were compared with final histopathological diagnosis. M371 was also assessed in controls to evaluate test performance. Secondary analyses investigated correlations between preoperative M371 levels and tumour size in non-metastatic patients, and between M371-levels and clinical stage in the entire GCT cohort. A cut-off of RQ > 5 (relative quantification) was used to calculate sensitivity, specificity, and predictive values. Results: M371 showed a sensitivity of 90.9% and specificity of 89.3%, outperforming in terms of sensitivity AFP (20.4%/96.4%), LDH (40.9%/96.4%), and β-HCG (43.1%/100%). Positive predictive value (PPV) and negative predictive value (NPV) were 93.0% and 86.2%, respectively. Sensitivity was 95% for non-seminomas and 87.5% for seminomas. In non-metastatic patients, M371 levels correlated with tumour size and were significantly higher in advanced stages (median RQ 1128.35 vs. 98.36; p = 0.015). Conclusions: M371 showed excellent diagnostic performance, even for small tumours, supporting its clinical use. Further studies are needed to define its role in treatment planning and follow-up. Full article

Survival rates for those with metastatic osteosarcoma (OS) have not improved over the last four decades. It is imperative that novel approaches to treating and curing OS be sought. We, therefore, turned our attention to Brusatol (Bru), a naturally occurring Nrf2 inhibitor reported to elicit anti-cancer effects in a multitude of tumour models. Importantly there is emerging evidence that Nrf2 is implicated in chemoradiotherapy resistance in OS and that inhibiting Nrf2 may represent a desirable route to treating OS. Surprisingly, using the human OS cell line, MG63, we actually found that Bru promoted cell growth. Compared to control, normoxic cultures, the application of Bru (50 nM) over 3 days led to an increase in cell number by approximately 1.7-fold. A similar outcome occurred for cells under hypoxic conditions, although the extent of cell growth was significantly less at around 1.3-fold. Furthermore, Bru prevented MG63 differentiation in response to co-treatment with the calcitriol analogue, EB1089, and the lipid growth factor, lysophosphatidic acid. The extent of inhibition was profound at approximately 2.8-fold. The application of the Nrf2 activator, dimethyl fumarate, did not rescue these phenotypes. Whilst Bru has shown promise in other cancer models, it would appear, from our findings, that this agent may not be suitable for the treatment of OS. Full article

This study investigated the effect of piranha solution etching duration on the shear bond strength of zirconia ceramics bonded to resin cement, comparing it to conventional sandblasting treatment. Fifty fully sintered zirconia specimens (6.0 mm diameter, 4.0 mm thickness) were prepared and randomly divided into five groups (n = 10): sandblasting control and piranha solution treatment for 1, 2, 3, and 4 min. Piranha solution was prepared by mixing 98% H₂SO₄ and 35% H₂O₂ in a 3:1 ratio. All specimens were bonded to resin composite cylinders using dual-cure resin cement. Shear bond strength testing was performed using a universal testing machine at a 0.5 mm/min crosshead speed. Failure modes were analyzed using a stereomicroscope and classified as adhesive, cohesive, or mixed failures. One-way ANOVA revealed significant differences between groups (p < 0.05). Tukey’s post hoc test showed that 1-min piranha treatment produced significantly lower bond strength (7.64 ± 2.02 MPa) compared to all other groups. The 2-min (15.17 ± 2.79 MPa), 3-min (14.99 ± 3.27 MPa), and 4-min (18.34 ± 3.15 MPa) piranha treatments showed no significant differences compared to sandblasting (15.41 ± 2.61 MPa). Failure mode analysis revealed 100% adhesive failures for the 1-min group, while all other groups showed 80% adhesive and 20% mixed failures. Piranha solution treatment duration significantly affected zirconia bonding performance. While 1-min treatment proved inadequate, 2–4 min treatments achieved bond strengths comparable to sandblasting. The findings suggest that piranha solution treatment for 2–4 min represents a viable alternative to sandblasting for zirconia surface preparation, with the 2-min protocol being the most efficient choice for clinical application. Full article

Radiation-induced intestinal injury (RIII), a severe complication of abdominopelvic radiotherapy, causes intestinal ischemia, ulcers, and necrosis, severely impacting patients’ quality of life. Currently, effective treatments are limited, and a specific cure remains elusive. Our previous research showed that lactoferrin (LF) can promote intestinal stem cell (ISC) proliferation and tissue repair; however, its oral administration is limited by rapid degradation in the gastric environment. In this study, we developed LF-loaded liposomal nanoparticles (Lip-LF) using a simple ethanol injection method. The optimal formulation (cholesterol/egg yolk lecithin ratio 2:8, LF concentration 12.5 mg/mL) achieved a drug-loading capacity of 6.8% and a narrow size distribution (0.2 < PDI < 0.4). In vitro experiments demonstrated that Lip-LF protected LF from pepsin degradation in simulated gastric fluid (SGF), retaining over 80% integrity after 120 min, while releasing in simulated intestinal fluid (SIF). In vivo imaging revealed prolonged gastrointestinal retention of Lip-LF compared to free LF. In a murine model of RIII (12 Gy whole-body irradiation), Lip-LF significantly restored villus counts, increased crypt height, and promoted goblet-cell regeneration. Immunohistochemical and qPCR analyses revealed enhanced ISCs proliferation and upregulation of repair-associated genes, including Pcna and Olfm4. These findings demonstrate that Lip-LF protects LF from gastric degradation and enhances its targeted delivery to the intestine, improving its therapeutic efficacy in repairing RIII. Lip-LF thus offers a promising strategy for managing RIII. Full article

Introduction: Canine sinonasal aspergillosis (SNA) can present singular as a primary disease or secondary to concurrent sinonasal pathology. We hypothesized that treatment response and prognosis differ between both forms, particularly when sinusitis is present. Methods: In this retrospective study, 30 dogs with SNA were categorized as either group pA (primary aspergillosis) or group sA (secondary aspergillosis; with additional sinonasal pathology). History, diagnostics, endoscopic therapeutic intervention of affected nose and sinus, and follow-up data were analyzed. Results: Group pA included 19/30 dogs (63%), with 15 dogs (79%) showing concurrent sinusitis. Group sA included 11/30 dogs (37%; additional conditions: foreign bodies, dental pathologies, frontal bone fracture). Only 2/11 sA dogs (18%) had sinusitis. Follow-ups in group pA were more frequent than in group sA (p = 0.04). Need for re-treatments differed significantly between groups (p = 0.02) and in dogs with sinusitis, regardless of group (p < 0.001). In group sA, treating the underlying condition plus single endoscopic debridement ± antifungal therapy led to clinical resolution in 11 of 12 dogs (92%). Conclusions: Primary SNA is frequently associated with sinusitis, requires aggressive repeated antifungal therapy, and may not achieve a definitive cure. Secondary SNA is usually confined to the nasal cavity, responds well to underlying condition treatment, carries better prognosis, and requires fewer antifungal treatments. Full article

Leishmaniasis is a parasitic disease caused by Leishmania spp., transmitted by sandflies, and endemic in 98 countries. Leishmania infantum, the main agent of visceral leishmaniasis in Europe, commonly infects both humans and animals, with dogs as the principal domestic reservoir. Clinical manifestations in dogs depend on the host immune response. A robust Th1 response facilitates macrophage activation and parasite control, while persistently elevated TNF-α and IL-6 can lead to chronic inflammation and tissue damage. Current treatments reduce parasite load but rarely achieve complete cure and are often associated with relapses and resistance. Artemisia annua, source of artemisinin, could be a promising alternative to canine leishmaniasis. Despite its potential, no published studies have investigated its effect specifically against Leishmania infantum as well as its possible dual action: antiparasitic and immunomodulation. We conducted in vitro evaluations of a standardized Artemisia annua extract. Leishmanicidal activity was assessed against both promastigote and amastigote stages, and cytokine modulation was evaluated in RAW 264.7 macrophages. The extract showed strong leishmanicidal activity without cytotoxicity and significantly reduced TNF-α and IL-6 levels under inflammatory conditions, and in both cases, efficiency was correlated with artemisinin content. These results support Artemisia annua as a promising safer therapeutic adjuvant candidate for canine leishmaniasis, targeting both the parasite and the host inflammatory response. Full article

Background: Alexander disease (AxD) is a rare severe leukodystrophy that has no cure to date. A pathogenic gain-of-function variant in the GFAP gene affects the astrocytes and subsequently the function of the white matter in the CNS. Methods: We retrospectively analyzed the most frequent symptoms of nine AxD cases, classified them according to published classifications, and described the need of care and support. Results: The description of the courses of disease of nine cases with AxD reflects the broad spectrum of different phenotypes of AxD, with often occurring apnoea. Data about care and support for AxD patients indicate a high and heterogeneous need of support. Treatment with steroids reduced symptoms in two patients. Some patients showed lasting improvement during their course of disease. Conclusions: The course of AxD is very heterogeneous. Thus, we extracted relevant key features to describe the severity of the disease, namely feeding problems, epilepsy, age-appropriate motor function, failure to thrive, age-appropriate language and apnoea. We recommend early evaluation for clinical care and support. For some AxD patients, treatment with steroids may alleviate symptoms. Further development of efficient treatments is necessary. Full article

Antimicrobial resistance is a global threat to public health. The growing resistance of bacteria to commonly used antibiotics necessitates the search for and development of alternative treatments. Bacteriophage (or phage) therapy fits this trend perfectly. Phages that selectively infect and kill bacteria might represent, in some cases, the last therapeutic option. This overview provides case examples and discusses the potential development of phage therapy, examining its ethical and legal considerations in the context of current clinical practices. Additionally, it explores the advantages of utilizing phage products in patients for whom existing therapeutic options are limited or unavailable. Further clinical studies are necessary to broaden the understanding of phages, their dosage, and a standardised delivery system. These efforts are essential to ensure that phage-based therapy is not viewed as experimentation but as a routine medical treatment. Bacterial viruses are unlikely to become a miracle cure or a panacea for infections, but they may find an important role in medicine. Full legalisation of this treatment could help solve the problem of multidrug-resistant infectious diseases on a global scale. Full article

Chronic hepatitis B virus (HBV) infection remains a major global health challenge, substantially contributing to liver-related morbidity and mortality. Background/Objectives: Developing therapeutic strategies that overcome immune tolerance and achieve functional cures is an urgent priority. Methods: In this study, we report a therapeutic vaccine comprising hepatitis B surface antigen (HBsAg) formulated with the dual adjuvant system CpG 1018S and QS-21. The immunogenicity and therapeutic efficacy of this vaccine were systematically evaluated in an rAAV8-HBV1.3-established chronic HBV mouse model. Results: The vaccine elicited a robust Th1-skewed immune response, characterized by elevated anti-HBs IgG2b titers and an increased IgG2b/IgG1 ratio. Notably, immunized mice showed markedly reduced circulating HBsAg levels. Mechanistically, the CpG 1018S and QS-21 adjuvant system enhanced dendritic cell activation, maturation, and antigen presentation, expanded HBV-specific CD4⁺ and CD8⁺ T cell populations, and attenuated the expression of the exhaustion markers TIM-3 and TIGIT. Additionally, immunized mice exhibited restored T cell polyfunctionality, with an increased secretion of effector cytokines, including TNF-α and IL-21. These responses collectively contributed to the reversal of T cell exhaustion and breakdown of immune tolerance, facilitating sustained viral suppression. Conclusions: Our findings demonstrate that the CpG 1018S/QS-21-adjuvanted vaccine induces potent humoral and cellular immunity against chronic HBV infection and represents a promising candidate for clinical chronic HBV (CHB) treatment. Full article

Objective: To investigate the influence of chitosan-based nano-silver fluoride (CNSF) treatment of tooth tissues on shear bond strength (SBS) of resin composite (RC) and resin-modified glass ionomer (RMGI) restorations. Methods: 90 extracted human molars were collected. Specimens were randomly assigned to three groups (n = 30): non-pretreated (NPT) pretreated with either CNSF or silver diamine fluoride (SDF). Each group was subdivided into two restorative subgroups (n = 15): RC and RMGI. Specimens in CNSF and SDF groups were pretreated with CNSF or SDF per their manufacturer’s instructions. Then specimens in RC subgroups were etched, treated with chlorhexidine cleanser, followed by adhesive application. Specimens in RMGI subgroups were treated with cavity conditioner only. A cylindrical restoration (2.38 mm θ × 2 mm height) of RC or RMGI restoration was fabricated with a standardized mold and light-cured on all specimens. After 5000 times of thermocycling between 5 °C and 55 °C with dwell times of 30 s intervals, SBS was measured using the Ultradent UltraTester. Data was analyzed statistically (α = 0.05) using ANOVA/Tukey’s comparisons. Results: No statistically significant difference in SBS among RC restorations in the three treatment groups: NPT (17.48 ± 3.96), CNSF (18.38 ± 5.59), and SDF (14.03 ± 6.56). For RMGI restorations, SBS was significantly (p < 0.05) higher in NPT (15.99 ± 3.59) compared to CNSF-treated (11.45 ± 5.48), but there was no significant difference between NPT and SDF-treated (14.27 ± 2.17) or between SDF- and CNSF-treated groups. Conclusions: No difference in SBS of resin composite restorations when the dentin tissue is pretreated with either chitosan-based nano-silver fluoride or silver diamine fluoride. However, SBS of RMGI was lowered when the dentin tissue was pretreated with CNSF. Full article

New York State and New York City (NYC) developed hepatitis C (HCV) elimination plans to reduce premature deaths and new infections. NYC Health + Hospitals (NYC H + H), the municipal healthcare system for NYC serving over a million individuals annually, designed electronic health record (EHR) tools that collaboratively facilitated screening, linkage, and tracking of patients diagnosed with HCV through to cure. This study reviews the impact of this group of EHR tools by comparing data on HCV testing, linkage, and cure for 12 months before tools were released and a second 12-month period coinciding with the release of tools. Indicators related to HCV screening, diagnoses, treatment initiation, and cure were assessed. All indicators reviewed improved following the implementation of EHR tools. The proportion of individuals screened increased from 34% pre-intervention to 46% during the implementation phase; the number of individuals on direct-acting antivirals increased by 11%; and the number of individuals reaching cure increased by 37%. Efforts to collaboratively develop custom interlinking EHR tools to establish a systematic process proved impactful. Integrating the needs and functions of different care settings and the structure of the local epidemic allowed for the successful development and implementation of impactful resources. Full article

We propose a life-expectancy pay-off function (LEP) for determining optimal cancer treatment within a control theory framework. The LEP averages life expectancy over all future outcomes, outcomes that are determined by key events during therapy such as tumour elimination (cure) and patient death (including treatment related mortality). We analyse this optimisation problem for tumours treated with chemotherapy using tumour growth models based on ordinary differential equations. To incorporate tumour elimination we draw on branching processes to compute the probability distribution of tumour population extinction. To demonstrate the approach, we apply the LEP framework to simplified one-compartment models of tumour growth that include three possible outcomes: cure, relapse, or death during treatment. Using Pontryagin’s maximum principle (PMP) we show that the best treatment strategies fall into three categories: (i) continuous treatment at the maximum tolerated dose (MTD), (ii) no treatment, or (iii) treat-and-stop therapy, where the drug is given at the MTD and then halted before the treatment (time) horizon. Optimal treatment strategies are independent of the time horizon unless the time horizon is too short to accommodate the most effective (treat-and-stop) therapy. For sufficiently long horizons, the optimal solution is either no treatment (when treatment yields no benefit) or treat-and-stop. Patients, thus, split into an untreatable class and a treatable class, with patient demographics, tumour size, tumour response, and drug toxicity determining whether a patient benefits from treatment. The LEP is in principle parametrisable from data, requiring estimation of the rates of each event and the associated life expectancy under that event. This makes the approach suitable for personalising cancer therapy based on tumour characteristics and patient-specific risk profiles. Full article