BACKGROUND: Proton beam therapy using pencil beam scanning is an advanced radiotherapy technique that utilises proton beams to precisely target tumours. It is known for its enhanced ability in sparing healthy tissue and potentially reducing toxicity. Clinical experience with pencil beam scanning in the treatment of mediastinal Hodgkin lymphoma remains limited. PATIENTS AND METHODS: This study aimed to evaluate the toxicity and outcomes of a prospectively observed cohort. A total of 162 patients were irradiated between May 2013 and December 2020, with a median age of 32 years (range: 18.4-79.2) and followed up until April 2024. The median applied dose was 30 GyE (range: 20-40). Deep inspiration breath hold was used in 146 patients to enhance targeting precision. RESULTS: The disease-free survival, overall survival and local control rates were 95.1 %, 98.8 % and 98.8 %, respectively. The median follow-up was 59.1 months (range: 4-120.1). The most common acute toxicities observed were oesophageal and skin toxicity. Grade 1 oesophageal mucositis occurred in 76 patients (47 %), grade 2 in 16 patients (10 %). Dermatitis of grade 1 and 2 was observed in 65 (40 %) and 4 (3 %) patients respectively. Grade 1 pulmonary toxicity presented in 8 patients (4.9 %), and grade 2 in one patient (0.6 %). The most predominant late toxicity was grade 2 hypothyroidism in 37 patients (23 %). Three patients (1.8 %) underwent coronary interventions during follow-up, and one patient was diagnosed with hepatocellular carcinoma 3 months post-RT. No unexpected acute or late toxicities were observed. CONCLUSION: Proton beam therapy using pencil beam scanning is a safe and effective technique in terms of toxicity and local control, even when irradiating mediastinal targets.
- MeSH
- Radiotherapy Dosage MeSH
- Adult MeSH
- Hodgkin Disease * radiotherapy mortality MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Mediastinal Neoplasms * radiotherapy mortality MeSH
- Prospective Studies MeSH
- Proton Therapy * adverse effects methods MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: Retroperitoneal lymph node dissection (RPLND) is crucial in managing metastatic germ cell tumors (GCTs), particularly post-chemotherapy. Given the long-term survival of these patients, perioperative morbidity is a significant concern. However, data on RPLND morbidity using predefined reporting standards are scarce. This study aims to address this gap by utilizing updated European Association of Urology (EAU) guidelines for standardized complication reporting. PATIENTS AND METHODS: A retrospective analysis was conducted on patients who underwent RPLND for GCTs between 2010 and 2022. 30-day complications were extracted from digital charts using a predefined procedure-specific catalog. Complications were graded using the Clavien-Dindo classification (CDC), and the Comprehensive Complication Index (CCI) was calculated for each patient. RESULTS: Sixty-nine men underwent RPLND at a median age of 32 years (IQR 25-38). Chemotherapy was administered to 64 patients (93 %), with 48 (70 %) having negative tumor markers. Median tumor diameter was 52 mm (IQR 35-83), and median operative time was 197 min (IQR 128-262). Unilateral template removal was performed in 55 patients (80 %). A total of 157 complications were reported in 66 patients (96 %), with anemia (33 %) and gastrointestinal issues (24 %) being the most common. Five patients (7.2 %) had "major" complications (CDC grade ≥ IIIa), and the median CCI was 12 (IQR 9-23). Using the CCI, the proportion of patients with a "major" complication burden increased to 14 %, compared to 8.5 % by CDC alone. The primary limitation of this study is its retrospective design and the limited 30-day follow-up period. CONCLUSION: Most patients experience postoperative complications after RPLND, though severe complications are rare. These findings could improve patient counseling when discussing testicular cancer therapy options.
- MeSH
- Adult MeSH
- Neoplasms, Germ Cell and Embryonal * surgery pathology MeSH
- Humans MeSH
- Lymph Node Excision * adverse effects MeSH
- Morbidity MeSH
- Follow-Up Studies MeSH
- Postoperative Complications * epidemiology etiology MeSH
- Prognosis MeSH
- Retroperitoneal Space surgery pathology MeSH
- Retrospective Studies MeSH
- Practice Guidelines as Topic * standards MeSH
- Testicular Neoplasms * surgery pathology MeSH
- Urology standards MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Scoping Review MeSH
Dysregulation of extracellular matrix (ECM) homeostasis plays a pivotal role in the accelerated degradation of cartilage, presenting a notable challenge for effective osteoarthritis (OA) treatment and cartilage regeneration. In this study, we introduced an injectable hydrogel based on streamlined-zinc oxide (ZnO), which is responsive to matrix metallopeptidase (MMP), for the delivery of miR-17-5p. This approach aimed to address cartilage damage by regulating ECM homeostasis. The ZnO/miR-17-5p composite functions by releasing zinc ions to attract native bone marrow mesenchymal stem cells, thereby fostering ECM synthesis through the proliferation of new chondrocytes. Concurrently, sustained delivery of miR-17-5p targets enzymes responsible for matrix degradation, thereby mitigating the catabolic process. Notably, the unique structure of the streamlined ZnO nanoparticles is distinct from their conventional spherical counterparts, which not only optimizes the rheological and mechanical properties of the hydrogels, but also enhances the efficiency of miR-17-5p transfection. Our male rat model demonstrated that the combination of streamlined ZnO, MMP-responsive hydrogels, and miRNA-based therapy effectively managed the equilibrium between catabolism and anabolism within the ECM, presenting a fresh perspective in the realm of OA treatment.
- MeSH
- Cell Differentiation * drug effects MeSH
- Chondrocytes metabolism drug effects cytology MeSH
- Cartilage * drug effects MeSH
- Extracellular Matrix * metabolism drug effects MeSH
- Homeostasis drug effects MeSH
- Hydrogels * chemistry MeSH
- Cartilage, Articular drug effects MeSH
- Rats MeSH
- Matrix Metalloproteinases metabolism MeSH
- Mesenchymal Stem Cells cytology drug effects metabolism MeSH
- MicroRNAs genetics metabolism MeSH
- Osteoarthritis therapy pathology MeSH
- Zinc Oxide chemistry MeSH
- Rats, Sprague-Dawley MeSH
- Regeneration MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Graphene-based materials (GBMs) have shown significant promise in cancer therapy due to their unique physicochemical properties, biocompatibility, and ease of functionalization. Their ability to target solid tumors, penetrate the tumor microenvironment (TME), and act as efficient drug delivery platforms highlights their potential in nanomedicine. However, the complex and dynamic nature of the TME, characterized by metabolic heterogeneity, immune suppression, and drug resistance, poses significant challenges to effective cancer treatment. GBMs offer innovative solutions by enhancing tumor targeting, facilitating deep tissue penetration, and modulating metabolic pathways that contribute to tumor progression and immune evasion. Their functionalization with targeting ligands and biocompatible polymers improves their biosafety and specificity, while their ability to modulate immune cell interactions within the TME presents new opportunities for immunotherapy. Given the role of metabolic reprogramming in tumor survival and resistance, GBMs could be further exploited in metabolism-targeted therapies by disrupting glycolysis, mitochondrial respiration, and lipid metabolism to counteract the immunosuppressive effects of the TME. This review focuses on discussing research studies that design GBM nanocomposites with enhanced biodegradability, minimized toxicity, and improved efficacy in delivering therapeutic agents with the intention to reprogram the TME for effective anticancer therapy. Additionally, exploring the potential of GBM nanocomposites in combination with immunotherapies and metabolism-targeted treatments could lead to more effective and personalized cancer therapies. By addressing these challenges, GBMs could play a pivotal role in overcoming current limitations in cancer treatment and advancing precision oncology.
- MeSH
- Graphite * chemistry therapeutic use MeSH
- Immunotherapy methods MeSH
- Drug Delivery Systems methods MeSH
- Humans MeSH
- Tumor Microenvironment * drug effects MeSH
- Neoplasms * drug therapy metabolism MeSH
- Nanocomposites * chemistry therapeutic use MeSH
- Antineoplastic Agents pharmacology therapeutic use MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND: Effective diabetes management requires a multimodal approach involving lifestyle changes, pharmacological treatment, and continuous patient education. Self-management demands can be overwhelming for patients, leading to lowered motivation, poor adherence, and compromised therapeutic outcomes. In this context, digital health apps are emerging as vital tools to provide personalized support and enhance diabetes management and clinical outcomes. OBJECTIVE: This study evaluated the impact of the digital health application Vitadio on glycemic control in patients with type 2 diabetes mellitus (T2DM). Secondary objectives included evaluating its effects on cardiometabolic parameters (weight, BMI, waist circumference, blood pressure, and heart rate) and self-reported measures of diabetes distress and self-management. METHODS: In this 6-month, 2-arm, multicenter, unblinded randomized controlled trial, patients aged 18 years or older diagnosed with T2DM were randomly assigned (1:1) to an intervention group (IG) receiving standard diabetes care reinforced by the digital health app Vitadio or to a control group (CG) provided solely with standard diabetes care. Vitadio provided a mobile-based self-management support tool featuring educational modules, motivational messages, peer support, personalized goal setting, and health monitoring. The personal consultant was available in the app to provide technical support for app-related issues. The primary outcome, assessed in the intention-to-treat population, was a change in glycated hemoglobin (HbA1c) levels at 6 months. Secondary outcomes included changes in cardiometabolic measures and self-reported outcomes. Data were collected in 2 study centers: diabetologist practice in Dessau-Roßlau and the University of Dresden. RESULTS: Between November 2022 and June 2023, a total of 276 patients were screened for eligibility, with 149 randomized to in intervention group (IG; n=73) and a control group (CG; n=76). The majority of participants were male (91/149, 61%). The dropout rate at month 6 was 19% (121/149). While both groups achieved significant HbA1c reduction at 6 months (IG: mean -0.8, SD 0.9%, P<.001; CG: mean -0.3, SD 0.7%, P=.001), the primary confirmatory analysis revealed statistically significant advantage of the IG (adjusted mean difference: -0.53%, SD 0.15, 95% CI -0.24 to -0.82; P<.001; effect size [Cohen d]=0.67, 95% CI 0.33-1). Significant between-group differences in favor of the IG were also observed for weight loss (P=.002), BMI (P=.001) and systolic blood pressure (P<.03). In addition, Vitadio users experienced greater reduction in diabetes-related distress (P<.03) and obtained more pronounced improvements in self-care practices in the areas of general diet (P<.001), specific diet (P<.03), and exercise (P<.03). CONCLUSIONS: This trial provides evidence for the superior efficacy of Vitadio in lowering the HbA1c levels in T2DM patients compared to standard care. In addition, Vitadio contributed to improvements in cardiometabolic health, reduced diabetes-related distress, and enhanced self-management, highlighting its potential as an accessible digital tool for comprehensive diabetes management. TRIAL REGISTRATION: German Clinical Trials Registry DRKS00027405; https://drks.de/search/de/trial/DRKS00027405.
- MeSH
- Diabetes Mellitus, Type 2 * blood therapy MeSH
- Adult MeSH
- Glycated Hemoglobin analysis MeSH
- Middle Aged MeSH
- Humans MeSH
- Mobile Applications * MeSH
- Self Care MeSH
- Self-Management MeSH
- Aged MeSH
- Telemedicine MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
BACKGROUND: Pembrolizumab plus lenvatinib is a treatment option for metastatic Renal Cell Carcinoma (mRCC). In the ARON-1 study we investigated we the real-world experiences gained from the use of this combination for mRCC. METHODS: We retrospectively investigated real-world clinical outcomes of mRCC patients receiving pembrolizumab plus lenvatinib within the ARON-1 study. Overall survival (OS) was calculated from the start of pembrolizumab plus lenvatinib to death for any cause. Progression-Free Survival (PFS) was defined as the time from the start of pembrolizumab to progression or death from any cause. Duration of response (DoR) was defined as the time from the start of pembrolizumab to disease progression or death, whichever occurred first, in patients who achieved complete remission (CR) or partial response (PR). Overall Response Rate (ORR) was defined as the proportion of patients who achieve a CR or PR per RECIST criteria. Adverse events were retrospectively collected from electronic and paper charts and categorized by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. RESULTS: Overall, we included 202 mRCC patients treated with pembrolizumab plus lenvatinib. The median follow-up time was 15.1 months. The median OS was not reached (NR), with a median PFS of 25.6 months and an Overall Response Rate (ORR) of 59%. The median Duration of Response (DoR) was 26.2 months. G3-G4 adverse events (AEs) were observed in 92 patients (46%), with hypertension being the most common AE (13%). CONCLUSIONS: Pembrolizumab plus lenvatinib is an effective and tolerable treatment for mRCC also in the real-world setting.
- MeSH
- Quinolines * therapeutic use administration & dosage pharmacology MeSH
- Adult MeSH
- Phenylurea Compounds * therapeutic use administration & dosage pharmacology MeSH
- Antibodies, Monoclonal, Humanized * therapeutic use administration & dosage pharmacology MeSH
- Carcinoma, Renal Cell * drug therapy mortality pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Metastasis MeSH
- Kidney Neoplasms * drug therapy pathology mortality MeSH
- Antineoplastic Combined Chemotherapy Protocols * therapeutic use MeSH
- Retrospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
PURPOSE: The aim of this study was to compare the accuracy of two spine models: the broken curve model and a new four tangent circles model. The modification concerns the adaptation of data acquisition to kinematic methods used in, e.g., gait and running analysis. METHOD: Plastic, movable spine model of human with flexible intervertebral disks (manufactured by Erler Zimmer GE3014) was used as the study material. Markers with a diameter of 5 mm were glued to each spinous process (from C7 to L5). The recording was performed with a 6-camera Vicon system. Two spine models were created: a broken curve model used, among others, in the Diers scanner, and an own model of 4 circles, similar to the model of circles used in X-ray and CT analysis. RESULTS: The errors in the position of the spinous processes were significantly smaller in the 4-circle model than in the broken curve model. They ranged from 0.01 to 6.5 mm in the lumbar section, from 0.004 to 3.1 mm in the thoracic section. The practical possibilities of using the four-circle model during the cinematographic analysis of gait and run should be checked. CONCLUSION: The four-circle model is more accurate than the broken curve model and can be used in the cinematographic analysis of the human spine movement.
Článek popisuje případ štěněte pomeraniana, které utrpělo zlomeninu kostí levého antebrachia. Malá a miniaturní plemena psů jsou ke vzniku zlomenin antebrachia predisponována. Díky anatomickým a biomechanickým specifikům je nutno přistupovat k řešení těchto traumat odlišně než u jiných zlomenin. Článek představuje použití orthogonal plating u konkrétního pacienta a snaží se objasnit filozofii této metody.
The article describes a case of a Pomeranian puppy that suffered a fracture of the left antebrachium. Toy and miniature breeds of dogs are predisposed to antebrachial fractures. Due to some anatomical and biomechanical specifics, it is necessary to approach these traumas differently than other fractures. The article presents the use of orthogonal plating in a specific patient and tries to clarify the philosophy of this method.
- MeSH
- Arm Bones * injuries MeSH
- Animal Diseases MeSH
- Dogs MeSH
- Fracture Fixation, Internal * veterinary MeSH
- Animals MeSH
- Check Tag
- Dogs MeSH
- Animals MeSH
- Publication type
- Case Reports MeSH
Plicní helmintózy patří k významným parazitárním onemocněním u domácích i volně žijících zvířat. Článek podává přehled významných plicních helmintů rodu Angiostrongylus, včetně jejich biologie, klinického významu a možností diagnostiky.
Helminthoses of the respiratory system represent clinically important parasitoses in domestic as well as wild animals. Article summarizes important species of lungworms in the genus Angiostrongylus, including their biology, clinical relevance and diagnostic approaches
Fyzická kondice psů je důležitým předpokladem pro bezpečné a efektivní provádění pohybu při uspokojování jejich denních potřeb. V sou- vislosti s kondicí je nezbytné znát pojmy postura a core a rozumět jim. Vlastní kondice sestává z šesti oblastí, které lze trénovat cvičením. Existuje celá řada cviků rozvíjejících jednotlivé oblasti kondice. Je běžné, že jedním cvikem můžeme rozvíjet více oblastí kondice. Kondici psa lze rozvíjet v každém věku, nicméně nesmíme ignorovat fyziologické zvláštnosti jednotlivých věkových stadií života psa.
The physical condition of dogs is an important prerequisite for safe and efficient exercise in meeting their daily needs. In relation to fitness, it is essential to know and understand the terms postural and core. Self-conditioning consists of six areas that can be trained through exercise. There are a number of exercises that develop each area of fitness. It is common to develop multiple areas of fitness with one exer- cise. A dog's fitness can be developed at any age, but we must not ignore the physiological peculiarities of the different ages of a dog's life.
