INTRODUCTION: The use of signal dogs for cancer detection is not yet routinely performed,but dogs and their powerful olfactory system have proven to be a unique and valuable tool for many lineages and are beginning to be incorporated into medical practice. This method has great advantages; the dog can detect a tumour in the human body already in preclinical stages, when the patient has no symptoms yet. The identification of cancer biomarkers to enable early diagnosis is a need for many types of cancer, whose prognosis is strongly dependent on the stage of the disease. However, this method also has its various pitfalls that must be taken into account. AIM: The aim of the study was to identify and highlight the factors that affect the level of detection accuracy, but also the conditions associated with olfactometric diagnosis. METHODS: The study included 48 dogs and 48 handlers, that were part of the training between 2016 and 2023.All those who started olfactometry training and remained in training for at least one year were included in the study. The dogs ranged in age from 8 months to 12 years and were of different races and sexes. After long-term observation, a qualitative analysis was performed and factors that may play a role in the early detection of the disease were listed. RESULTS: The results of the search for the different factors have been compiled into two groups, focussing on the actual handling of the patient biological sample from collection, processing, storage until transport, preparation of the sample,and detection. Focus on the actual work and behaviour of the dog and handler. CONCLUSION: There are many factors; however, it is worth addressing them because the canine sense of smell is one of the possible uses as a diagnostic method.

• Publication type
• Journal Article MeSH

Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer's Disease (AD). To address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-diagnosed AD cases, and 613,671 controls. We considered three approaches to account for the different X-chromosome inactivation (XCI) states in females, i.e. random XCI, skewed XCI, and escape XCI. We did not detect any genome-wide significant signals (P ≤ 5 × 10-8) but identified seven X-chromosome-wide significant loci (P ≤ 1.6 × 10-6). The index variants were common for the Xp22.32, FRMPD4, DMD and Xq25 loci, and rare for the WNK3, PJA1, and DACH2 loci. Overall, this well-powered XWAS found no genetic risk factors for AD on the non-pseudoautosomal region of the X-chromosome, but it identified suggestive signals warranting further investigations.

• MeSH
• Alzheimer Disease * genetics   MeSH
• Genome-Wide Association Study methods   MeSH
• Genetic Predisposition to Disease genetics   MeSH
• X Chromosome Inactivation genetics   MeSH
• Polymorphism, Single Nucleotide genetics   MeSH
• Humans MeSH
• Chromosomes, Human, X * genetics   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

PURPOSE: High-dose intravenous glucocorticoids are the standard first-line treatment in active, moderate to severe and severe thyroid eye disease (TED). We evaluate the usefulness of clinical activity score (CAS) and thyroid-stimulating immunoglobulin (TSI) as predictors and/or post-treatment markers of corticoresistance in patients with TED and the effect of rituximab in second-line treatment. METHODS: We enrolled 236 patients with an active TED into this retrospective single-tertiary-center cohort study. All patients were initially treated with high-dose systemic glucocorticoids. Rituximab was later administered to 29 of 42 corticoresistant patients. RESULTS: The CAS of the corticoresistant patients was significantly higher both before (p = 0.0001) and after (p = <0.0001) first-line treatment compared to the corticosensitive group. ROC analysis established the cut-point value as CAS ≥ 2.5 with a sensitivity of 96.3%, specificity of 57.5% and area under the curve of 82.8%. In 22 patients treated with rituximab, CAS gradually decreased to zero values without reactivation during extended follow-up. There was no difference in the TSI of corticosensitive and corticoresistant patients before or after first-line therapy. CONCLUSION: CAS ≥ 2, after first-line treatment, could be used as a corticoresistance marker. Corticoresistant patients should be subject to long-term follow-up for early detection of reactivation to reduce the delay to second-line treatment. Rituximab is a well-tolerated choice of second-line treatment and has a long-lasting effect on disease activity. Although TSI is a valuable biomarker of Graves' disease and TED activity, according to our results, TSI cannot be used as a marker of corticoresistance.

• MeSH
• Adult MeSH
• Glucocorticoids therapeutic use   MeSH
• Graves Ophthalmopathy * drug therapy   blood   MeSH
• Immunoglobulins, Thyroid-Stimulating blood   MeSH
• Immunologic Factors therapeutic use   MeSH
• Drug Resistance * MeSH
• Middle Aged MeSH
• Humans MeSH
• Retrospective Studies MeSH
• Rituximab * therapeutic use   MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Poly(ɛ-caprolactone) (PCL) is a biocompatible, biodegradable, and highly mechanically resilient FDA-approved material (for specific biomedical applications, e.g. as drug delivery devices, in sutures, or as an adhesion barrier), rendering it a promising candidate to serve bone tissue engineering. However, in vivo monitoring of PCL-based implants, as well as biodegradable implants in general, and their degradation profiles pose a significant challenge, hindering further development in the tissue engineering field and subsequent clinical adoption. To address this, photo-cross-linkable mechanically resilient PCL networks are developed and functionalized with a radiopaque monomer, 5-acrylamido-2,4,6-triiodoisophthalic acid (AATIPA), to enable non-destructive in vivo monitoring of PCL-based implants. The covalent incorporation of AATIPA into the crosslinked PCL networks does not significantly affect their crosslinking kinetics, mechanical properties, or thermal properties, but it increases their hydrolysis rate and radiopacity. Complex and porous 3D designs of radiopaque PCL networks can be effectively monitored in vivo. This work paves the way toward non-invasive monitoring of in vivo degradation profiles and early detection of potential implant malfunctions.

• MeSH
• Biocompatible Materials chemistry   MeSH
• Mice MeSH
• Polyesters * chemistry   MeSH
• Porosity MeSH
• Materials Testing MeSH
• Tissue Engineering methods   MeSH
• Tissue Scaffolds * chemistry   MeSH
• Absorbable Implants MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Acute kidney injury (AKI) due to gentamicin nephrotoxicity is a significant concern in clinical medicine, particularly in patients receiving prolonged or high-dose gentamicin therapy. Gentamicin is an aminoglycoside antibiotic frequently used in the treatment of a range of bacterial infections. However, its use is associated with nephrotoxicity which can manifest as AKI. Due to this, it is crucial to diagnose promptly and manage treatment effectively. Ongoing studies are therefore focusing on non-protein-coding RNAs as potential biomarkers for AKI. Numerous microRNAs (miRNAs) have been implicated in gentamicin-induced nephrotoxicity and AKI. They participate in pathways associated with inflammation, cell death, and oxidative stress and each of these factors play critical roles in the development of gentamicin-induced kidney injury. Research studies have demonstrated changes in the expression levels of these miRNAs in response to gentamicin exposure both in vitro and in in vivo models, as well as in human clinical trials involving patients receiving gentamicin therapy. The dysregulation of these miRNAs correlates with the severity of kidney injury and may serve as sensitive biomarkers for early detection and monitoring of AKI induced by gentamicin.

• MeSH
• Acute Kidney Injury * chemically induced   diagnosis   MeSH
• Anti-Bacterial Agents * adverse effects   MeSH
• Biomarkers * MeSH
• Gentamicins * adverse effects   MeSH
• Humans MeSH
• MicroRNAs * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Minimal residual disease (MRD) is one of the most important prognostic factors in multiple myeloma (MM) and a valid surrogate for progression-free survival (PFS) and overall survival (OS). Recently, MRD negativity was approved as an early clinical endpoint for accelerated drug approval in MM. Nevertheless, there is limited evidence of MRD utility in real-world setting. In this retrospective multicenter study, we report outcomes of 331 newly diagnosed MM patients with MRD evaluation at Day+100 after autologous stem cell transplantation using flow cytometry with a median limit of detection of 0.001%. MRD negativity was reached in 47% of patients and was associated with significantly prolonged median PFS (49.2 months vs. 18.4 months; hazard ratios (HR) = 0.37; p < 0.001) and OS (not reached vs. 74.9 months; HR = 0.50; p = 0.007). Achieving MRD negativity was associated with PFS improvements regardless of age, International Staging System (ISS) stage, lactate dedydrogenase (LDH) level, or cytogenetic risk. Importantly, MRD positive patients benefited from lenalidomide maintenance versus no maintenance (18-months PFS: 81% vs. 46%; HR = 0.24; p = 0.002) while in MRD negative patients such benefit was not observed (p = 0.747). The outcomes of our real-world study recapitulate results from clinical trials including meta-analyses and support the idea that MRD positive patients profit more from lenalidomide maintenance than MRD negative ones.

• MeSH
• Transplantation, Autologous MeSH
• Adult MeSH
• Lenalidomide administration & dosage   therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Multiple Myeloma * diagnosis   mortality   therapy   pathology   MeSH
• Prognosis MeSH
• Flow Cytometry * methods   MeSH
• Retrospective Studies MeSH
• Neoplasm, Residual * diagnosis   MeSH
• Aged MeSH
• Neoplasm Staging MeSH
• Hematopoietic Stem Cell Transplantation methods   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

BACKGROUND AND OBJECTIVE: While prostate cancer (PCa) incidence and mortality rates continue to rise, early detection of PCa remains highly controversial, and the research landscape is rapidly evolving. Existing systematic reviews (SRs) and meta-analyses (MAs) provide valuable insights, but often focus on single aspects of early detection, hindering a comprehensive understanding of the topic. We aim to fill this gap by providing a comprehensive SR of contemporary SRs covering different aspects of early detection of PCa in the European Union (EU) and the UK. METHODS: On June 1, 2023, we searched four databases (Medline ALL via Ovid, Embase, Web of Science, and Cochrane Central Register of Controlled Trials) and Google Scholar. To avoid repetition of previous studies, only SRs (qualitative, quantitative, and/or MAs) were considered eligible. In the data, common themes were identified to present the evidence systematically. KEY FINDINGS AND LIMITATIONS: We identified 1358 citations, resulting in 26 SRs eligible for inclusion. Six themes were identified: (1) invitation: men at general risk should be invited at >50 yr of age, and testing should be discontinued at >70 yr or with <10 yr of life expectancy; (2) decision-making: most health authorities discourage population-based screening and instead recommend a shared decision-making (SDM) approach, but implementation of SDM in clinical practice varies widely; decision aids help men make more informed and value-consistent screening decisions and decrease men's intention to attempt screening, but these do not affect screening uptake; (3) acceptance: facilitators for men considering screening include social prompting by partners and clinician recommendations, while barriers include a lack of knowledge, low-risk perception, and masculinity attributes; (4) screening test and algorithm: prostate-specific antigen-based screening reduces PCa-specific mortality and metastatic disease in men aged 55-69 yr at randomisation if screened at least twice; (5) harms and benefits: these benefits come at the cost of unnecessary biopsies, overdiagnosis, and subsequent overtreatment; and (6) future of screening: risk-adapted screening including (prebiopsy) risk calculators, magnetic resonance imaging, and blood- and urine-based biomarkers could reduce these harms. To enable a comprehensive overview, we focused on SRs. These do not include the most recent prospective studies, which were therefore incorporated in the discussion. CONCLUSIONS AND CLINICAL IMPLICATIONS: By identifying consistent and conflicting evidence, this review highlights the evidence-based foundations that can be built upon, as well as areas requiring further research and improvement to reduce the burden of PCa in the EU and UK. PATIENT SUMMARY: This review of 26 reviews covers various aspects of prostate cancer screening such as invitation, decision-making, screening tests, harms, and benefits. This review provides insights into existing evidence, highlighting the areas of consensus and discrepancies, to guide future research and improve prostate cancer screening strategies in Europe.

• MeSH
• Early Detection of Cancer * MeSH
• European Union * MeSH
• Humans MeSH
• Prostatic Neoplasms * diagnosis   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Geographicals
• United Kingdom MeSH

Úvod: Burzy jsou tíhové váčky vystlané synoviální vrstvou buněk a obsahují tekutinu podobnou kloubní synovii. Jejich účelem je snižovat mechanické namáhaní (tření) v místech kontaktu šlach s kostí, kloubním pouzdrem anebo vazem. Vlivem různých příčin se může burza zanítit a způsobovat pacientovi obtíže. Burzitidu je možné diagnostikovat zavedením metodiky časného SPECT/CT při vyšetření skeletu. Kazuistiky: Uvádím zde tři pacienty, dva přišli s bolestí kolenních kloubů trvající několik měsíců a jeden s bolestí v oblasti bederní páteře, u kterých byla diagnostikovaná burzitis na třífázové scintigrafii skeletu. Závěr: Dle BOSS klasifikace patří všechny burzitidy do tvz. skupiny C (neboli extraoseální). Tyto patologie na scintigrafii skeletu odhalí pouze provedení SPECT/CT ve fázi blood poolu.

Introduction: Bursae are weight-bearing sacs lined with a synovial layer of cells and contain a fluid similar to joint synovium. Their purpose is to reduce mechanical stress (friction) in the points of contact of tendons with bone, joint capsule or ligament. Due to various reasons, the bursa can become inflamed and cause difficulties for the patient. It is possible to diagnose bursitis by introducing early SPECT/CT methodology during the examination of the skeleton. Case reports: Three patients are presented here, two with pain in the knee joints lasting several months and one with pain in the area of the lumbar spine, who were diagnosed with bursitis on three-phase skeletal scintigraphy. Conclusion: According to the BOSS classification, all bursitis belongs to what is known as group C (or extraosseous). These pathologies on bone scintigraphy can only be detected by performing SPECT/CT in the blood pool phase.

• Keywords
• SPECT/CT krevního poolu,
• MeSH
• Back Pain diagnostic imaging   pathology   MeSH
• Bursitis * diagnostic imaging   MeSH
• Knee Joint diagnostic imaging   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Radionuclide Imaging MeSH
• Single Photon Emission Computed Tomography Computed Tomography * MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

Gastroschíza je vrozená rozštěpová vada břišní stěny charakterizovaná eventerací střevních kliček obvykle pravostranným paraumbilikálním defektem. Prenatální detekce gastroschízy není díky pokročilým ultrazvukovým metodám obtížná. Časný záchyt vady je klíčový pro optimalizaci prenatální péče i následný management. Prognóza této vady je dobrá a dlouhodobý stav dětí je příznivý, nicméně 10–15 % případů má komplikovaný průběh s vysokým rizikem neonatální mortality či závažné morbidity. Časný záchyt umožňuje efektivní monitorování vývoje plodu, posouzení rizika rozvoje komplikací a jejich minimalizace plánováním porodu v perinatologickém centru s dostupností intenzivní neonatologické péče a možností okamžité chirurgické intervence.

Gastroschisis is a congenital abdominal wall defect characterized by the eventration of bowel loops through a right-sided paraumbilical opening. Prenatal detection of gastroschisis is generally straightforward due to advanced ultrasound techniques, and it is essential for optimizing both prenatal care and subsequent management. The prognosis for this condition is generally favorable, with positive long-term outcomes for most children. However, 10–15% of cases may follow a complicated course with an elevated risk of neonatal mortality or significant morbidity. Early detection enables effective monitoring of fetal development, risk assessment for potential complications, and risk minimization by planning childbirth at a tertiary center equipped with intensive neonatal care and the possibility of prompt surgical intervention.

Alzheimerova choroba je nejčastější příčinou demence a včasná diagnostika je klíčová pro zahájení léčby. Porucha čichu, zejména schopnost identifikace pachů, byla opakovaně identifikována jako raný příznak neurodegenerativních změn a může pomoci při časné detekci Alzheimerovy choroby. Psychofyzické testy čichu, jako je Sniffin’ Sticks, (SST) University of Pennsylvania Smell Identification Test (UPSIT), či test parfémovaných fixů (OMT), jsou spolehlivými nástroji pro hodnocení čichových funkcí a mají potenciál doplnit tradiční neuropsychologické testy. Kombinace čichových a kognitivních testů významně zvyšuje přesnost predikce nástupu demence.

Koutná V, Štěpánek L, Trajerová R, Janout V, Janoutová J. Olfactory impairment as a biomarker in early diagnosis of Alzheimer’s disease in primary care Alzheimer’s disease is the most common cause of dementia and early diagnosis is key to initiating treatment. Olfactory dysfunction, particularly the ability to discriminate odors, has been repeatedly identified as an early sign of neurodegenerative changes and may aid in the early detection of Alzheimer’s disease. Psychophysical olfactory tests such as the Sniffin’ Sticks (SST), University of Pennsylvania Smell Identification Test (UPSIT) or the Odorized Marker Test (OMT) are reliable tools for assessing olfactory function and have potential to complement traditional neuropsychological tests. The combination of olfactory and cognitive tests significantly increases the accuracy of predicting the onset of dementia.