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.

• MeSH
• Gait Analysis * methods   MeSH
• Models, Anatomic * MeSH
• Lumbar Vertebrae physiology   MeSH
• Biomechanical Phenomena MeSH
• Gait * physiology   MeSH
• Humans MeSH
• Spine * physiology   anatomy & histology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH

Článek se zabývá stručným popisem zdravotních problémů, na něž má vliv výživa. Nejčastějšími zdravotními problémy králíků se vztahem k výživě jsou onemocnění gastrointestinálního traktu (trichobezoáry, enteritidy, enterotoxemie), obezita a syndrom onemocnění dentice (a s tím související problémy). Na tyto problémy pak navazují další problémy a změny chování králíků. V závěru je stručně uvedeno správné složení krmné dávky králíků v zájmovém chovu.

The article deals with a description of the health problems affected by nutrition. The most common nutrition-related health problems in rabbits are gastrointestinal diseases (trichobezoars, enteritis, enterotoxaemia), obesity and dentition syndrome (and related problems). These problems are then followed by other problems and behavioural changes in rabbits. In conclusion, the correct composition of rabbit diets for pet rabbits is briefly outlined.

• MeSH
• Animal Husbandry MeSH
• Enteropathogenic Escherichia coli MeSH
• Protein-Losing Enteropathies etiology   veterinary   MeSH
• Animal Nutritional Physiological Phenomena MeSH
• Rabbits MeSH
• Digestive System Diseases * etiology   veterinary   MeSH
• Animal Diseases * MeSH
• Animal Welfare MeSH
• Diet, Plant-Based MeSH
• Animals MeSH
• Check Tag
• Rabbits MeSH
• Animals MeSH
• Publication type
• Review MeSH

Trvalá antikoagulační terapie u pacientů v chronickém hemodialyzačním programu přináší řadu klinických a farmakologických výzev. Fibrilace síní, často komplikovaná nerovnováhou mezi pro- a antikoagulačními mechanismy, vyžaduje individuální přístup s ohledem na vysoké riziko krvácivých komplikací a trombembolismu. V posledních letech přibývá důkazů o použití přímých perorálních antikoagulancií (DOAC) u této populace na úkor warfarinu, jehož podávání nebylo prokázáno jako efektivní, a je navíc spojeno se zvýšeným rizikem krvácení a negativním vlivem na kalcium-fosfátový metabolismus. Tato práce se zaměřuje na zhodnocení současných možností antikoagulace s důrazem na nefrologické a koagulační aspekty, včetně přehodnocení zastaralých režimů a potenciální aplikace moderních přístupů.

Long-term anticoagulation therapy in patients on chronic hemodialysis presents a few clinical and pharmacological challenges. Atrial fibrillation, often complicated by an imbalance between pro- and anticoagulant factors, requires an individualized approach considering the high risk of bleeding complications and thromboembolism. In recent years, we have an increasing evidence for the use of direct oral anticoagulants (DOAC) in this population at the expense of warfarin The administration of warfarin has not been proven to be effective and is also associated with an increased risk of bleeding and a negative effect on calcium-phosphate metabolism. This work focuses on the evaluation of current anticoagulation options with an emphasis on nephrological and coagulation aspects, including a re-evaluation of outdated regimens and the potential application of modern approaches

• Keywords
• apixaban,
• MeSH
• Renal Insufficiency, Chronic * complications   therapy   MeSH
• Renal Dialysis MeSH
• Atrial Fibrillation * drug therapy   MeSH
• Heparin, Low-Molecular-Weight administration & dosage   therapeutic use   MeSH
• Humans MeSH
• Pyrazoles therapeutic use   MeSH
• Risk Factors MeSH
• Thromboembolism drug therapy   prevention & control   MeSH
• Warfarin therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Tento přehledový článek se zaměřuje na základní principy technologií umělé inteligence (AI), možnosti jejich využití v medicíně a na příklady aplikací, které již byly začleněny do klinické praxe. Diskutuje také klíčové výzvy včetně etických otázek, jako je ochrana soukromí pacientů, algoritmická bias a problém transparentnosti modelů AI. Článek zdůrazňuje nutnost integrace AI do medicíny způsobem, který zajistí bezpečnost a důvěryhodnost, a současně vyzdvihuje význam vzdělávání zdravotnických profesionálů v oblasti AI. Umělá inteligence nabízí potenciál ke zlepšení přesnosti diagnostiky, efektivity péče a podpory při klinickém rozhodování, přičemž optimálních výsledků lze dosáhnout spoluprací mezi lékaři a systémy AI.

This review article focuses on the fundamental principles of artificial intelligence (AI) technologies, their utilisation in medicine, and examples of applications that have already been incorporated into clinical practice. It also discusses key challenges, including ethical issues such as patient data privacy, algorithmic bias, and the transparency problem of AI models. The article emphasizes the necessity of integrating AI into medicine in a manner that ensures safety and trustworthiness, while underscoring the importance of educating healthcare professionals about AI. Artificial intelligence offers the potential to enhance diagnostic accuracy, the efficiency of care, and support for clinical decision-making, with optimal outcomes being achieved through collaboration between physicians and AI systems.

• MeSH
• Algorithms MeSH
• Medicine * MeSH
• Humans MeSH
• Nephrology MeSH
• Artificial Intelligence * ethics   MeSH
• Large Language Models MeSH
• Computer Security MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Urologické komplikace jsou častým a významným problémem u dialyzovaných pacientů. Infekce močových cest (IMC), urolitiáza, benigní hyperplazie prostaty (BHP) a erektilní dysfunkce (ED) negativně ovlivňují kvalitu života a mohou komplikovat nefrologickou péči, včetně transplantace ledviny. Tento přehledový článek shrnuje patofyziologii, diagnostické přístupy a terapeutické možnosti urologických komplikací u dialyzovaných pacientů na základě aktuálních studií a klinických doporučení. Infekce močových cest jsou u dialyzovaných pacientů běžné a mohou mít atypický průběh. Urolitiáza se v této populaci vyskytuje méně často, ale její management je specifický vzhledem k metabolickým změnám spojeným s chronickým onemocněním ledvin. BHP je u dialyzovaných mužů často poddiagnostikována kvůli snížené diuréze, přičemž po transplantaci může vést k akutní močové retenci. Erektilní dysfunkce má vysokou prevalenci a multifaktoriální etiologii, včetně hormonálních, cévních a neurologických změn. Urologické komplikace u dialyzovaných pacientů vyžadují včasnou diagnostiku a multidisciplinární přístup. Optimalizace léčby může snížit morbiditu, zlepšit kvalitu života a předejít komplikacím po transplantaci ledviny. Další výzkum je nutný pro optimalizaci nefrologicko-urologické péče v této specifické populaci.

Urological complications are a common and significant issue in dialysis patients. Urinary tract infections (UTIs), urolithiasis, benign prostatic hyperplasia (BPH), and erectile dysfunction (ED) negatively impact the quality of life and may complicate nephrological care, including kidney transplantation. This review article summarizes the pathophysiology, diagnostic approaches, and therapeutic options for urological complications in dialysis patients based on current studies and clinical recommendations. Urinary tract infections are frequent in dialysis patients and may present with atypical manifestations. Urolithiasis occurs less commonly in this population, but its management is specific due to metabolic changes associated with chronic kidney disease. BPH is often underdiagnosed in dialysis patients due to reduced diuresis, whereas after transplantation, it may lead to acute urinary retention. Erectile dysfunction has a high prevalence and a multifactorial etiology, including hormonal, vascular, and neurological changes. Urological complications in dialysis patients require early diagnosis and a multidisciplinary approach. Optimizing treatment can reduce morbidity, improve quality of life, and prevent complications after kidney transplantation. Further research is needed to enhance nephro-urological care in this specific population.

• MeSH
• Kidney Failure, Chronic complications   MeSH
• Renal Dialysis * MeSH
• Erectile Dysfunction physiopathology   therapy   MeSH
• Prostatic Hyperplasia diagnosis   therapy   MeSH
• Urinary Tract Infections * diagnosis   drug therapy   prevention & control   MeSH
• Humans MeSH
• Urolithiasis diagnosis   therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

The aim of this study was to test the hypothesis that individuals with an increase in HbA1c (i.e. above the regular but below the diabetic threshold) exhibit an impairment in the Achilles tendon structure and walking capacity, due to the adverse effect of the advanced glycation end-product. One hundred fifty-eight participants matched for gender, age, physical activity and BMI, were divided in two cohorts based on the HbA1c level: normal HbA1c (NGH; <39 mmol/molHb; n = 79) and altered HbA1c (AGH; >=39 mmol/molHb; n = 79). Each participant performed several walking trials to evaluate the kinematic parameters during walling at the self-selected speed and a quantitative MRI scan of the Achilles tendon (AT) to obtain its intrinsic characteristics (i.e. T2* relaxation time short and long component). The AT T2* relaxation time short component (a parameter related to the tendon collagen quality) was reduced in AGH compared to NGH. Furthermore, AGH exhibited a slower self-selected walking speed (NGH: 1.59 ± 0.18 m/s; AGH:1.54 ± 0.16 m/s) and a shorter stride length (NGH: 1.59 ± 0.13 m; AGH:1.55 ± 0.11 m). Our data suggest that a non-pathological increase in HbA1c is able to negatively affect AT collagen quality and walking capacity in healthy people. These results highlight the importance of glycemic control, even below the pathological threshold. Since diabetes could alter several biological pathways, further studies are necessary to determine which mechanisms and their timing, regarding the HbA1c rise, affect tendon composition and, consequently, walking capacity.

• MeSH
• Achilles Tendon * diagnostic imaging   physiology   metabolism   MeSH
• Biomechanical Phenomena MeSH
• Walking * physiology   MeSH
• Diabetes Mellitus diagnosis   MeSH
• Adult MeSH
• Glycated Hemoglobin * metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Glycation End Products, Advanced metabolism   MeSH
• Healthy Volunteers MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND AND AIMS: Data on upadacitinib therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBD-U) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as an induction therapy in pediatric UC or IBD-U. METHODS: In this multicenter retrospective study, children treated with upadacitinib for induction of remission of active UC or IBD-U from 30 centers worldwide were enrolled. Demographic, clinical, and laboratory data, as well as adverse events (AEs), were recorded at Week 8 post-induction. RESULTS: One hundred children were included (90 UC and 10 IBD-U, median age 15.6 [interquartile range 13.3-17.1] years). Ninety-eight were previously treated with biologic therapies, and 76 were treated with ≥2 biologics. At the end of the 8-week induction period, clinical response, clinical remission, and corticosteroid-free clinical remission (CFR) were observed in 84%, 62%, and 56% of the children, respectively. Normal C-reactive protein and fecal calprotectin (FC) <150 mcg/g were achieved in 75% and 50%, respectively. Combined CFR and FC remission was observed in 18/46 (39%) children with available data at 8 weeks. Adverse events were recorded in 37 children, including 1 serious AE of an appendiceal neuroendocrine tumor. The most frequent AEs were hyperlipidemia (n = 13), acne (n = 12), and infections (n = 10, 5 of whom with herpes viruses). CONCLUSIONS: Upadacitinib is an effective induction therapy for refractory pediatric UC and IBD-U. Efficacy should be weighed against the potential risks of AEs.

• MeSH
• C-Reactive Protein analysis   MeSH
• Child MeSH
• Heterocyclic Compounds, 3-Ring * therapeutic use   adverse effects   MeSH
• Remission Induction methods   MeSH
• Induction Chemotherapy methods   MeSH
• Leukocyte L1 Antigen Complex analysis   MeSH
• Humans MeSH
• Adolescent MeSH
• Retrospective Studies MeSH
• Colitis, Ulcerative * drug therapy   MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

OBJECTIVES: Elderly hospitalized patients with inflammatory bowel disease (IBD) flare and concurrent Clostridioides difficile infection (CDI) are considered at high risk of IBD-related complications. We aimed to evaluate the short-,intermediate-, and long-term post-discharge complications among these patients. METHODS: A retrospective multicenter cohort study assessing outcomes of elderly individuals (≥60 years) hospitalized for an IBD flare who were tested for CDI (either positive or negative) and discharged. The primary outcome was the 3-month post-discharge IBD-related complication rates defined as steroid dependency, re-admissions (emergency department or hospitalization), IBD-related surgery, or mortality. We assessed post-discharge IBD-related complications within 6 month and mortality at 12 month among secondary outcomes. Risk factors for complication were assessed by multivariable logistic regression. RESULTS: In a cohort of 654 patients hospitalized for IBD {age 68.9 (interquartile range [IQR]): 63.9-75.2 years, 60.9% ulcerative colitis (UC)}, 23.4% were CDI-positive. Post-discharge complication rates at 3 and 6 months, and 12 months mortality, did not differ significantly between CDI-positive and CDI-negative patients (32% vs 33.1%, p = 0.8; 40.5% vs 42.5%, p = 0.66; and 4.6% vs 8%, p = 0.153, respectively). The Charlson comorbidity index was the only significant risk factor for complications within 3 months (aOR 1.1), whereas mesalamine (5-aminosalicylic acid [5-ASA]) use was protective (aOR 0.6). An UC diagnosis was the sole risk factor for complication at 6 months (aOR 1.5). Clostridioides difficile infection did not significantly impact outcomes or interact with IBD type. CONCLUSIONS: In elderly IBD patients hospitalized for IBD flare and subsequently discharged, a concurrent CDI infection was not associated with post-discharge IBD-related complications or mortality up to 1 year.

• MeSH
• Clostridioides difficile MeSH
• Hospitalization statistics & numerical data   MeSH
• Inflammatory Bowel Diseases * complications   MeSH
• Clostridium Infections * complications   epidemiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Patient Discharge MeSH
• Retrospective Studies MeSH
• Risk Factors MeSH
• Aged MeSH
• Symptom Flare Up MeSH
• Patient Readmission statistics & numerical data   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Myasthenia gravis (MG) je chronické autoimunitní onemocnění, které vzniká působením autoprotilátek na struktury nervosvalového spojení, zejména na acetylcholinový receptor. Myasthenia gravis lze relativně dobře léčit kombinovanou imunosupresivní léčbou, která je ale zatížena řadou nežádoucích účinků a bezpečnostních rizik a u nemalé části pacientů je onemocnění na léčbu refrakterní. Tento článek si klade za cíl shrnout patofyziologické mechanismy MG a nové typy léčiv, které na tyto mechanismy cílí. Jedná se o léčbu zaměřenou na B Lymfocyty a plazmatické buňky, inhibitory komplementu a antagonisty neonatálního receptoru imunoglobulinů (neonatal Fc receptor, neonatal fragment crystalizable receptor, FcRn). Některé z těchto Léčeb jsou již schváleny a další klinické studie probíhají.

Myasthenia gravis (MG) is a chronic autoimmune disease that is mediated by autoantibodies against neuromuscular junction structures, especially against acetylcholine receptors. MG can be relatively well treated with immunosuppressive therapy but is burdened by a number of side effects and safety risks and considerable number of patients are refractory to therapy. This article aims to summarize the pathophysiological mechanisms of MG and to describe new types of drugs specifically targeting these mechanisms. These include therapies targeting B-lymphocytes and plasma cells, complement inhibitors and neonatal immunoglobulin receptor antagonists (neonatal Fc receptor, FcRn). Some of these treatments are already approved on the basis of successful clinical trials and further studies are ongoing.

• MeSH
• Antibodies, Monoclonal, Humanized pharmacology   therapeutic use   MeSH
• Complement Inactivating Agents pharmacology   therapeutic use   MeSH
• Clinical Studies as Topic MeSH
• Humans MeSH
• Antibodies, Monoclonal pharmacology   therapeutic use   MeSH
• Myasthenia Gravis * therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH