• Publikační typ
• tisková chyba MeSH

INTRODUCTION: It is hypothesized that systemically administered antibiotics penetrate wound sites more effectively during negative pressure wound therapy (NPWT). However, there is a lack of clinical data from patients who receive NPWT for deep sternal wound infection (DSWI) after open-heart surgery. Here, we evaluated vancomycin penetration into exudate in this patient group. PATIENTS AND METHODS: For this prospective observational study, we enrolled 10 consecutive patients treated with NPWT for post-sternotomy DSWI. On the first sampling day, serum and exudate samples were synchronously collected at 0 (pre-dose), 0.5, 1, 2, 3 and 6 h after vancomycin administration. On the following three consecutive days, additional samples were collected, only before vancomycin administration. RESULTS: The ratio of average vancomycin concentration in wound exudate to in serum was higher for free (unbound) (1.51 ± 0.53) than for total (bound + unbound) (0.91 ± 0.29) concentration (p = 0.049). The percentage of free vancomycin was higher in wound exudate than serum (0.79 ± 0.19 vs. 0.46 ± 0.16; p = 0.04). Good vancomycin wound penetration was maintained on the following three days (vancomycin trough exudate-to-serum concentration ratio > 1). The total hospital stay was significantly longer in patients with DSWI (46 ± 11.6 days) versus without DSWI (14 ± 11.7 days) (p < 0.001). There was no in-hospital or 90-day mortality. Two patients experienced late DSWI recurrence. All-cause mortality was 4.8% during a median follow-up of 2.5 years. CONCLUSION: Vancomycin effectively penetrates wound exudate in patients receiving NPWT for DSWI after open-heart surgery.The protocol for this study was registered at ClinicalTrials.gov on July 16, 2024 (NCT06506032).

• MeSH
• antibakteriální látky * farmakokinetika   aplikace a dávkování   MeSH
• exsudáty a transsudáty metabolismus   mikrobiologie   MeSH
• infekce chirurgické rány * MeSH
• kardiochirurgické výkony * škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• senioři MeSH
• sternotomie * škodlivé účinky   MeSH
• sternum chirurgie   MeSH
• terapie ran pomocí řízeného podtlaku * metody   MeSH
• vankomycin * aplikace a dávkování   farmakokinetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

The Institute for Safe Medication Practices and the American Society of Health-System Pharmacists have advocated for removing all injectable promethazine from inpatient and outpatient settings; however, this drug is still being used despite the risk for tissue necrosis, gangrene, and possible amputation when it inadvertently is given by the subcutaneous or intra-arterial route. This article describes alternative injectable medications that can be selected based on patient comorbidities, indications, and clinician experience.

• MeSH
• injekce subkutánní MeSH
• injekce MeSH
• lidé MeSH
• promethazin * aplikace a dávkování   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Publikace se zaměřuje na farmakorezistenci u schizofrenie, deprese, úzkosti a obsedantně-kompulzivní poruchy. Určeno odborné veřejnosti.

• MeSH
• duševní poruchy MeSH
• léková rezistence MeSH
• psychotropní léky MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Psychiatrie
• NLK Obory
• psychiatrie
• psychofarmakologie

BACKGROUND: Presensitized patients with circulating donor-specific antibodies (DSAs) before transplantation are at risk for antibody-mediated rejection (AMR). Peritransplant desensitization mitigates but does not eliminate the alloimmune response. We examined the possibility that subthreshold AMR activity undetected by histology could be operating in some early biopsies. METHODS: Transcriptome of kidney allograft biopsies performed within the first month in presensitized patients (DSA+) who had received desensitization and did not develop active/probable AMR by histology (R-) was compared with biopsies showing active/probable AMR (R+/DSA+). As negative controls, biopsies without rejection by histology in patients without DSA at transplantation were used (R-/DSA-). RNA sequencing from biopsies selected from the biobank was used in cohort 1 (n = 32) and microarray, including the molecular microscope (Molecular Microscope Diagnostic System [MMDx]) algorithm, in recent cohort 2 (n = 30). RESULTS: The transcriptome of R-/DSA+ was similar to R+/DSA+ as these groups differed in 14 transcripts only. Contrarily, large differences were found between both DSA+ groups and negative controls. Fast gene set enrichment analyses showed upregulation of the immune system in both DSA+ groups (gene ontology terms: adaptive immune response, humoral immune response, antigen receptor-mediated signaling, and B-cell receptor signaling or complement activation) when compared with negative controls. MMDx assessment in cohort 2 classified 50% of R-/DSA+ samples as AMR and found no differences in AMR molecular scores between R+ and R- DSA+ groups. In imlifidase desensitization, MMDx series showed a gradual increase in AMR scores over time. CONCLUSIONS: Presensitized kidney transplant recipients exhibited frequent molecular calls of AMR in biopsy-based transcript diagnostics despite desensitization therapy and negative histology.

• Publikační typ
• časopisecké články MeSH

Papillary thyroid carcinoma (PTC) represents ~80% of all thyroid cancers, most frequently presenting in women in the third and fourth decade of life. The first clinical manifestation of PTC commonly includes a palpable mass in the thyroid area or cervical lymphadenopathy in cases of metastatic disease. Hematogenous distant metastases are a sign of an advanced stage of the tumour. The present study reported an extremely rare occurrence of solitary metastasis of a PTC in the left breast of a 63-year-old male patient, mimicking primary male breast cancer (MBC). The presence of a male breast lesion that did not follow the typical imaging criteria for MBC aroused suspicion of a different primary origin. The combination of imaging methods, laboratory findings and fine-needle aspiration techniques enabling cytological and histopathological examination, with the use of a wide panel of immunohistochemical markers, is crucial to establishing a definitive and correct diagnosis.

• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

• Konspekt
• Patologie. Klinická medicína

Cardiac involvement (CI) in phosphomannomutase 2-congenital disorders of glycosylation (PMM2-CDG) is part of the multisystemic presentation contributing to high mortality rates. The most common cardiac manifestations are pericardial effusion, cardiomyopathy, and structural heart defects. A genotype-phenotype correlation with organ involvement has not yet been described. We analyzed clinical, biochemical, and molecular genetic data of 222 patients from eight European centers and characterized the natural course of patients with CI. Fifty-seven patients (45 children) presented with CI, of whom 24 died (median age 21 months, standard deviation 49.8). Pericardial effusion was the most frequent manifestation (55.4%), occurring mostly within the first 6 months of life. The most common pathogenic variants in patients with CI were p.(Arg141His) in 74%, followed by p.(Val231Met) in 36%, which is 3.5 times higher than in PMM2-CDG patients without CI (p < 0.0001). Twenty-one out of 36 patients with p.(Val231Met) had CI; among them, 15 died, compared to 33 out of 166 patients without p.(Val231Met) who had CI (p < 0.0001). Nine out of 33 patients died (p = 0.0015), indicating greater clinical severity. Furthermore, the p.(Val231Met) variant is predominant in Eastern Europe, suggesting a founder effect. Cardiac complications in PMM2-CDG patients are common and serious. The variant p.(Val231Met) profoundly influences the extent of CI and mortality rates. Therefore, we recommend cardiac surveillance be included in the follow-up protocols for PMM2-CDG.

• MeSH
• dítě MeSH
• fenotyp * MeSH
• fosfotransferasy (fosfomutasy) * genetika   nedostatek   MeSH
• genetické asociační studie MeSH
• kardiomyopatie genetika   MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mutace MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• stupeň závažnosti nemoci MeSH
• vrozené poruchy glykosylace * genetika   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: Patients with severe aortic stenosis present frequently (∼50%) with concomitant obstructive coronary artery disease. Current guidelines recommend combined surgical aortic valve replacement (SAVR) and coronary artery bypass grafting (CABG) as the preferred treatment. Transcatheter aortic valve implantation (TAVI) and fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) represent a valid treatment alternative. We aimed to test the non-inferiority of FFR-guided PCI plus TAVI versus SAVR plus CABG in patients with severe aortic stenosis and complex coronary artery disease. METHODS: This international, multicentre, prospective, open-label, non-inferiority, randomised controlled trial was conducted at 18 tertiary medical centres across Europe. Patients (aged ≥70 years) with severe aortic stenosis and complex coronary artery disease, deemed feasible for percutaneous or surgical treatment according to the on-site Heart Team, were randomly assigned (1:1) to FFR-guided PCI plus TAVI or SAVR plus CABG according to a computer-generated sequence with random permuted blocks sizes stratified by site. The primary endpoint was a composite of all-cause mortality, myocardial infarction, disabling stroke, clinically driven target-vessel revascularisation, valve reintervention, and life-threatening or disabling bleeding at 1 year post-treatment. The trial was powered for non-inferiority (with a margin of 15%) and if met, for superiority. The primary and safety analyses were done per an intention-to-treat principle. This trial is registered with ClinicalTrials.gov (NCT03424941) and is closed. FINDINGS: Between May 31, 2018, and June 30, 2023, 172 patients were enrolled, of whom 91 were assigned to the FFR-guided PCI plus TAVI group and 81 to the SAVR plus CABG group. The mean age of patients was 76·5 years (SD 3·9). 118 (69%) of 172 patients were male and 54 (31%) patients were female. FFR-guided PCI plus TAVI resulted in favourable outcomes for the primary endpoint (four [4%] of 91 patients) versus SAVR plus CABG (17 [23%] of 77 patients; risk difference -18·5 [90% CI -27·8 to -9·7]), which was below the 15% prespecified non-inferiority margin (pnon-inferiority<0·001). FFR-guided PCI plus TAVI was superior to SAVR plus CABG (hazard ratio 0·17 [95% CI 0·06-0·51]; psuperiority<0·001), which was driven mainly by all-cause mortality (none [0%] of 91 patients vs seven (10%) of 77 patients; p=0·0025) and life-threatening bleeding (two [2%] vs nine [12%]; p=0·010). INTERPRETATION: The TCW trial is the first trial to compare percutaneous treatment versus surgical treatment in patients with severe aortic stenosis and complex coronary artery disease, showing favourable primary endpoint and mortality outcomes with percutaneous treatment. FUNDING: Isala Heart Centre and Medtronic.

• MeSH
• aortální stenóza * chirurgie   komplikace   MeSH
• chirurgická náhrada chlopně metody   MeSH
• frakční průtoková rezerva myokardu * MeSH
• koronární angioplastika * metody   MeSH
• koronární bypass * metody   MeSH
• lidé MeSH
• nemoci koronárních tepen * chirurgie   komplikace   terapie   MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transkatetrální implantace aortální chlopně * metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnocení ekvivalence MeSH
• multicentrická studie MeSH
• srovnávací studie MeSH

BACKGROUND: Advances in paediatric type 1 diabetes management and increased use of diabetes technology have led to improvements in glycaemia, reduced risk of severe hypoglycaemia, and improved quality of life. Since 1993, progressively lower HbA1c targets have been set. The aim of this study was to perform a longitudinal analysis of HbA1c, treatment regimens, and acute complications between 2013 and 2022 using data from eight national and one international paediatric diabetes registries. METHODS: In this longitudinal analysis, we obtained data from the Australasian Diabetes Data Network, Czech National Childhood Diabetes Register, Danish Registry of Childhood and Adolescent Diabetes, Diabetes Prospective Follow-up Registry, Norwegian Childhood Diabetes Registry, England and Wales' National Paediatric Diabetes Audit, Swedish Childhood Diabetes Registry, T1D Exchange Quality Improvement Collaborative, and the SWEET initiative. All children (aged ≤18 years) with type 1 diabetes with a duration of longer than 3 months were included. Investigators compared data from 2013 to 2022; analyses performed on data were pre-defined and conducted separately by each respective registry. Data on demographics, HbA1c, treatment regimen, and event rates of diabetic ketoacidosis and severe hypoglycaemia were collected. ANOVA was performed to compare means between registries and years. Joinpoint regression analysis was used to study significant breakpoints in temporal trends. FINDINGS: In 2022, data were available for 109 494 children from the national registries and 35 590 from SWEET. Between 2013 and 2022, the aggregated mean HbA1c decreased from 8·2% (95% CI 8·1-8·3%; 66·5 mmol/mol [65·2-67·7]) to 7·6% (7·5-7·7; 59·4mmol/mol [58·2-60·5]), and the proportion of participants who had achieved HbA1c targets of less than 7% (<53 mmol/mol) increased from 19·0% to 38·8% (p<0·0001). In 2013, the aggregate event rate of severe hypoglycaemia rate was 3·0 events per 100 person-years (95% CI 2·0-4·9) compared with 1·7 events per 100 person-years (1·0-2·7) in 2022. In 2013, the aggregate event rate of diabetic ketoacidosis was 3·1 events per 100 person-years (95% CI 2·0-4·8) compared with 2·2 events per 100 person-years (1·4-3·4) in 2022. The proportion of participants with insulin pump use increased from 42·9% (95% CI 40·4-45·5) in 2013 to 60·2% (95% CI 57·9-62·6) in 2022 (mean difference 17·3% [13·8-20·7]; p<0·0001), and the proportion of participants using continuous glucose monitoring (CGM) increased from 18·7% (95% CI 9·5-28·0) in 2016 to 81·7% (73·0-90·4) in 2022 (mean difference 63·0% [50·3-75·7]; p<0·0001). INTERPRETATION: Between 2013 and 2022, glycaemic outcomes have improved, parallel to increased use of diabetes technology. Many children had HbA1c higher than the International Society for Pediatric and Adolescent Diabetes (ISPAD) 2022 target. Reassuringly, despite targeting lower HbA1c, severe hypoglycaemia event rates are decreasing. Even for children with type 1 diabetes who have access to specialised diabetes care and diabetes technology, further advances in diabetes management are required to assist with achieving ISPAD glycaemic targets. FUNDING: None. TRANSLATIONS: For the Norwegian, German, Czech, Danish and Swedish translations of the abstract see Supplementary Materials section.

• MeSH
• diabetes mellitus 1. typu * epidemiologie   krev   farmakoterapie   MeSH
• dítě MeSH
• glykovaný hemoglobin * analýza   MeSH
• hypoglykemie epidemiologie   MeSH
• hypoglykemika * terapeutické užití   MeSH
• kojenec MeSH
• krevní glukóza * analýza   MeSH
• lidé MeSH
• longitudinální studie MeSH
• mladiství MeSH
• předškolní dítě MeSH
• registrace * statistika a číselné údaje   MeSH
• regulace glykemie statistika a číselné údaje   metody   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• buněčný tracking metody   MeSH
• fluor chemie   MeSH
• fluorokarbony MeSH
• kontrastní látky MeSH
• pohyb buněk MeSH
• zobrazování fluorovou magnetickou rezonancí MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• radiologie, nukleární medicína a zobrazovací metody
• NLK Publikační typ
• kolektivní monografie

BACKGROUND: Psychotherapy outcomes are typically measured in terms of symptom relief. However, this method might overlook important changes from clients' perspectives when they are asked to report on them. A more client-centred approach might bring a deeper understanding of psychotherapy outcomes. We aimed to evaluate the outcomes identified by clients within qualitative psychotherapy research. METHODS: The PsycArticles, PsycInfo, and MEDLINE Complete databases were searched for English language studies published until Nov 11, 2023. Additional studies were identified through references in the primary studies and previous meta-analyses or systematic reviews. Search terms were related to psychotherapy and counselling, clients' or patients' experiences, psychotherapy outcomes and changes, post-treatment perspectives, and types of qualitative methods. Qualitative studies on client-identified outcomes of individual psychotherapy were included. Findings related to clients' perceptions of psychotherapy outcomes were extracted (by ML and checked by TR and LT) and analysed (by all authors) using the descriptive-interpretative meta-analytic approach. All authors have personally experienced psychotherapy as clients. This study was pre-registered with PROSPERO (CRD42021277330). FINDINGS: We included 177 studies in the qualitative meta-analysis, from 24 countries, including descriptions from 2908 clients. Most of the studies were of good quality; they covered a wide range of therapeutic approaches and diagnoses. The descriptions of psychotherapy outcomes were classified into 60 meta-categories and grouped into ten clusters. These clusters related to clients' relational and social functioning; their emotional functioning; self-awareness, self-understanding, and more adaptive cognitive processing; behavioural functioning; developing their own resources; clients' attitudes towards themselves; generally embracing life; symptom and problem change; and more general wellbeing. The tenth cluster was outcomes that could not be clearly attributed to psychotherapy, which was considered outside the scope of this study. INTERPRETATION: The meta-analysis showed that clients value outcome dimensions beyond symptom reduction, such as deeper self-understanding, enhanced self-agency, and greater social engagement. By examining psychotherapy outcomes across various diagnoses and therapeutic approaches, we highlight limitations in traditional outcome measures, showing the need for more comprehensive, client-centred assessment tools and the value of incorporating qualitative methods into understanding dimensions of change. FUNDING: European Union.

• MeSH
• duševní poruchy terapie   psychologie   MeSH
• kvalitativní výzkum MeSH
• lidé MeSH
• psychoterapie * metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH

BACKGROUND: Skeletal muscle alterations are associated with higher mortality and morbidity in patients with liver cirrhosis. Assessing these changes seems to be a promising method for identifying patients at a high risk of poor outcomes following liver transplantation (LT). This is particularly important given the current global shortage of organ donors. However, evidence of the impact of these alterations on the prognosis of patients undergoing LT is inconclusive. The aim of our prospective study was to evaluate the impact of skeletal muscle changes, reflected in sarcopenia, myosteatosis and metabolic changes in the calf muscles, on perioperative outcomes and long-term survival after LT. We also sought to determine the posttransplant evolution of the resting muscle metabolism. METHODS: We examined 134 adult LT candidates. Of these, 105 underwent LT. Sarcopenia and myosteatosis were diagnosed by measuring the skeletal muscle index and mean psoas muscle radiation attenuation, respectively, which were obtained from computed tomography (CT) scans taken during pretransplant assessment. Additionally, patients underwent 31P MR spectroscopy (MRS) of the calf muscles at rest before LT and 6, 12 and 24 months thereafter. The median follow-up was 6 years. RESULTS: Patients with abnormal 31P MRS results and CT-diagnosed myosteatosis prior to LT had significantly worse long-term survival after LT (hazard ratio (HR), 3.36; 95% confidence interval (CI), 1.48-7.60; p = 0.0021 and HR, 2.58; 95% CI, 1.06-6.29; p = 0.03, respectively). Multivariable analysis showed that abnormal 31P MR spectra (HR, 3.40; 95% CI, 1.50-7.71; p = 0.003) were a better predictor of worse long-term survival after LT than myosteatosis (HR, 2.78; 95% CI, 1.14-6.78; p = 0.025). Patients with abnormal 31P MR spectra had higher blood loss during LT (p = 0.038), required a higher number of red blood cell transfusions (p = 0.006) and stayed longer in ICU (p = 0.041) and hospital (p = 0.007). Myosteatosis was associated with more revision surgeries following LT (p = 0.038) and a higher number of received red blood cell transfusion units (p = 0.002). Sarcopenia had no significant effect on posttransplant patient survival. An improvement in the resting metabolism of the calf muscles was observed at 12 and 24 months after LT. CONCLUSIONS: Abnormal 31P MRS results of calf muscles were superior to CT-based diagnosis of myosteatosis and sarcopenia in predicting perioperative complications and long-term survival after LT. Resting muscle metabolism normalized 1 year after LT in most recipients.

• MeSH
• dospělí MeSH
• kosterní svaly * diagnostické zobrazování   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie * metody   MeSH
• počítačová rentgenová tomografie * metody   MeSH
• prognóza MeSH
• prospektivní studie MeSH
• sarkopenie etiologie   metabolismus   MeSH
• senioři MeSH
• transplantace jater * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: This study was performed to compare the efficacy and safety of PreserFlo MicroShunt (PMS) implantation with mitomycin C (MMC) applied by sub-tenon injection versus conventional application by MMC-soaked sponges. METHODS: This retrospective, 1-year cohort study included 100 eyes of 100 patients with glaucoma who underwent PMS implantation with MMC (0.4 mg/ml) delivered either by sub-tenon injection (50 eyes) or via soaked sponges (50 eyes). The primary outcome measure at 1 year was intraocular pressure (IOP) reduction, with complete success defined as an IOP reduction of ≥ 20% and achieving a target IOP of ≤ 21 or 18 mmHg without the use of medication. Secondary outcomes, including corneal endothelial cell density (CECD) loss, the number of medications, and complications, were assessed and compared between the groups. RESULTS: Sustained reductions in mean IOP were observed in both groups over the 1-year follow-up, with no significant differences between the groups. The complete success rate, with a target IOP of ≤ 21 mmHg after 1 year, was 19.3% in the sponge group and 26.4% in the injection group. The qualified success rate was 59.0% and 87.4% in the sponge and injection groups, respectively. A longer survival rate was observed in the injection group than in the sponge group when IOP was below 21 mmHg. The mean CECD significantly decreased (P < 0.01) from baseline to each postoperative follow-up time point in both groups. At 1 year postoperatively, the percentage of total CECD loss was 8.1% in the sponge group and 8.0% in the injection group. However, no significant differences in mean CECD values, the number of medications, or adverse events were found between the groups. CONCLUSIONS: PMS implantation with sub-tenon injection of MMC was comparable in terms of efficacy and safety to traditional MMC delivery via soaked sponges. However, the injection group demonstrated a significantly higher success rate than the sponge group.

• Publikační typ
• časopisecké články MeSH

Wilson disease (WD) primarily presents with hepatic and neurological symptoms. While hepatic symptoms typically precede the neurological manifestations, copper accumulates in the brain already in this patient group and leads to subclinical brain MRI abnormalities including T2 hyperintensities and atrophy. This study aimed to assess brain morphological changes in mild hepatic WD. WD patients without a history of neurologic symptoms and decompensated cirrhosis and control participants underwent brain MRI at 3T scanner including high-resolution T1-weighted images. A volumetric evaluation was conducted on the following brain regions: nucleus accumbens, caudate, pallidum, putamen, thalamus, amygdala, hippocampus, midbrain, pons, cerebellar gray matter, white matter (WM), and superior peduncle, using Freesurfer v7 software. Whole-brain analyses using voxel- and surface-based morphometry were performed using SPM12. Statistical comparisons utilized a general linear model adjusted for total intracranial volume, age, and sex. Twenty-six WD patients with mild hepatic form (30 ± 9 years [mean age ± SD]); 11 women; mean treatment duration 13 ± 12 (range 0-42) years and 28 healthy controls (33 ± 9 years; 15 women) were evaluated. Volumetric analysis revealed a significantly smaller pons volume and a trend for smaller midbrain and cerebellar WM in WD patients compared to controls. Whole-brain analysis revealed regions of reduced volume in the pons, cerebellar, and lobar WM in the WD group. No significant differences in gray matter density or cortical thickness were found. Myelin or WM in general seems vulnerable to low-level copper toxicity, with WM volume loss showing promise as a marker for assessing brain involvement in early WD stages.

• MeSH
• bílá hmota patologie   diagnostické zobrazování   MeSH
• dospělí MeSH
• hepatolentikulární degenerace * patologie   diagnostické zobrazování   MeSH
• játra patologie   diagnostické zobrazování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mladý dospělý MeSH
• mozek * patologie   diagnostické zobrazování   MeSH
• šedá hmota patologie   diagnostické zobrazování   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Hand and foot osteosarcoma represents ~1% of all diagnosed cases of osteosarcoma. The rarity of osteosarcoma of the hand and foot leads to frequent misdiagnosis, delayed diagnosis or incorrect treatments, which can lead to fatal consequences. Typically, salvaging the affected limb is the treatment of choice, and with the use of chemotherapy, 60-65% of patients with osteosarcoma can be treated without amputation. Due to its rarity, misdiagnosis and treatment delays are common, yet detailed reviews and analyses of such cases are limited. The present retrospective cohort study aimed to review and analyze cases of osteosarcoma located in the hand and foot. From January 2007 to January 2019, 11 patients were treated at the Masaryk Memorial Cancer Institute Sarcoma Center (Brno, Czechia), 5 cases affected the hand and 6 affected the foot. A total of 6 male patients and 5 female patients, with a mean age of 30.9±16.74 years, were diagnosed with hand or foot osteosarcoma. The mean follow-up period was 90.36±66.14 months. The mean tumor size detected during diagnosis was 4.29±1.81 cm. Osteoblastic osteosarcoma was the most common histopathological type, accounting for 4 cases (33.4%). A majority of the osteosarcomas were identified as high grade (81.8%). A total of 5 patients experienced misdiagnoses following their initial biopsy, with 2 patients initially receiving treatment outside the Masaryk Memorial Cancer Institute Sarcoma Center. The most frequently encountered misdiagnosis was giant-cell tumor of the bone. A total of 3 patients underwent limb amputation and 2 patients developed lung metastasis and succumbed to the disease. The disease-free survival period and overall survival rate were calculated using Kaplan-Meier survival analysis. The mean disease-free survival period was 82.83±60.05 months, while the overall survival rate was 72%, with a mean survival time of 90.36±56.73 months. In summary, an examination of a case series involving 11 patients diagnosed with osteosarcoma of the hand and foot was conducted. The treatment approach, clinical characteristics and patient outcomes were described. A total of four case studies of patients with osteosarcoma in the hand or foot were presented. Misdiagnosis of this disease may result in the inappropriate treatment being administered to patients, therefore, the correct and rapid diagnosis of disease is necessary for effective treatment of hand and foot osteosarcomas.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Vaccination against 5 prominent meningococcal serogroups (A/B/C/W/Y) is necessary for broad disease protection. We report immunopersistence through 4 years after a 2-dose (6-month interval) pentavalent MenABCWY primary vaccine series and safety and immunogenicity of a booster administered 4 years after primary vaccination. METHODS: This randomized, active-controlled, observer-blinded study was conducted in the United States and Europe. In stage 1, healthy MenACWY vaccine-naive or -experienced 10- to 25-year-olds were randomized 1:2 to receive MenABCWY and placebo or MenB-fHbp and MenACWY-CRM. Eligible participants were randomly selected to participate in stage 2, which was an open-label immunopersistence and booster extension. Immunogenicity was assessed through serum bactericidal antibody using human complement (hSBA) assays with serogroups A/C/W/Y (MenA/C/W/Y) and 4 primary serogroup B (MenB) test strains. Immunogenicity endpoints included hSBA seroprotection rates through 48 months after primary vaccination and 1 month after the booster. Safety endpoints included booster reactogenicity events and adverse events (AEs). RESULTS: Of 1379 eligible participants, 353 entered stage 2; 242 completed the 48-month blood draw after primary vaccination and 240 completed the booster vaccination phase. MenA/C/W/Y seroprotection rates remained high for 4 years following a 2-dose MenABCWY primary series (MenACWY-naive, 62.0 %-100.0 %; MenACWY-experienced, 98.7 %-100.0 %) and trended higher than those after a single MenACWY-CRM dose (MenACWY-naive, 38.1 %-95.2 %; MenACWY-experienced, 89.7 %-100.0 %). Corresponding seroprotection rates against MenB remained stable and generally higher than baseline (MenABCWY, 18.2 %-36.6 %; MenB-fHbp, 16.2 %-31.9 % across strains). Following a booster, seroprotection rates against all 5 serogroups were ≥ 93.8 % across groups. Most booster dose reactogenicity events were mild or moderate in severity, and AEs were infrequent. CONCLUSIONS: Immune responses remained high for MenA/C/W/Y and above baseline for MenB through 4 years after the MenABCWY primary series, with robust responses for all 5 serogroups observed following a booster. The MenABCWY booster had an acceptable safety and tolerability profile consistent with the primary series. NCT03135834.

• MeSH
• dítě MeSH
• dospělí MeSH
• imunogenicita vakcíny MeSH
• komplement imunologie   MeSH
• lidé MeSH
• meningokokové infekce * prevence a kontrola   imunologie   MeSH
• meningokokové vakcíny * imunologie   škodlivé účinky   aplikace a dávkování   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Neisseria meningitidis imunologie   MeSH
• protilátky bakteriální * krev   MeSH
• sekundární imunizace * metody   MeSH
• séroskupina MeSH
• vakcíny konjugované imunologie   aplikace a dávkování   škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Evropa MeSH
• Spojené státy americké MeSH

INTRODUCTION/AIMS: Prospective, randomized, controlled trials of intravenous immunoglobulin (IVIG) maintenance therapy in myasthenia gravis (MG) are lacking. In this trial, we evaluated the safety and efficacy of caprylate/chromatography-purified IVIG; (IGIV-C) in patients with generalized MG undergoing standard care. METHODS: Sixty-two patients enrolled in this phase 2, multicenter, international, randomized trial (1:1 IGIV-C [2 g/kg loading dose; 1 g/kg every 3 weeks through week 21] or placebo). Efficacy was assessed by changes in Quantitative MG (QMG) score at week 24 versus baseline (primary endpoint) and percentage of patients with clinical improvement in QMG, MG Composite (MGC), and MG-Activities of Daily Living (MG-ADL) scores (secondary endpoints). Safety assessments reported all adverse events (AEs). RESULTS: The change in QMG at 24 weeks was -5.1 for IGIV-C and -3.1 for placebo (p = .187). Seventy percent of patients in the IGIV-C group had improvement in MG-ADL (≥2-point decrease) versus 40.6% in the placebo group (p = .025). Patients showing clinical improvement in QMG and MGC (≥3-point decrease) were 70.0% for IGIV-C versus 59.4% for placebo (p = .442) and 60.0% for IGIV-C versus 53.1% for placebo (p = .610). IGIV-C was well tolerated; serious AEs were similar between arms. Three of four MG exacerbations requiring hospitalizations occurred in the IGIV-C arm with one death. DISCUSSION: Several efficacy parameters showed numerical results greater than those seen in the placebo group. This was a small study and may have been underpowered to see significant differences. Additional studies may be warranted to fully determine the efficacy of IVIG maintenance therapy in MG.

• MeSH
• autoprotilátky krev   MeSH
• činnosti denního života MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• imunologické faktory terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• intravenózní imunoglobuliny * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myasthenia gravis * farmakoterapie   MeSH
• prospektivní studie MeSH
• receptory cholinergní * imunologie   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

PURPOSE OF REVIEW: A critical evaluation of contemporary literature regarding the role of big data, artificial intelligence, and digital technologies in precision cardio-oncology care and survivorship, emphasizing innovative and groundbreaking endeavors. RECENT FINDINGS: Artificial intelligence (AI) algorithm models can automate the risk assessment process and augment current subjective clinical decision tools. AI, particularly machine learning (ML), can identify medically significant patterns in large data sets. Machine learning in cardio-oncology care has great potential in screening, diagnosis, monitoring, and managing cancer therapy-related cardiovascular complications. To this end, large-scale imaging data and clinical information are being leveraged in training efficient AI algorithms that may lead to effective clinical tools for caring for this vulnerable population. Telemedicine may benefit cardio-oncology patients by enhancing healthcare delivery through lowering costs, improving quality, and personalizing care. Similarly, the utilization of wearable biosensors and mobile health technology for remote monitoring holds the potential to improve cardio-oncology outcomes through early intervention and deeper clinical insight. Investigations are ongoing regarding the application of digital health tools such as telemedicine and remote monitoring devices in enhancing the functional status and recovery of cancer patients, particularly those with limited access to centralized services, by increasing physical activity levels and providing access to rehabilitation services. SUMMARY: In recent years, advances in cancer survival have increased the prevalence of patients experiencing cancer therapy-related cardiovascular complications. Traditional cardio-oncology risk categorization largely relies on basic clinical features and physician assessment, necessitating advancements in machine learning to create objective prediction models using diverse data sources. Healthcare disparities may be perpetuated through AI algorithms in digital health technologies. In turn, this may have a detrimental effect on minority populations by limiting resource allocation. Several AI-powered innovative health tools could be leveraged to bridge the digital divide and improve access to equitable care.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Renal cell carcinoma (RCC) is a disease typified by anomalies in cell metabolism. The function of mitochondria, including subunits of mitochondrial respiratory complex II (CII), in particular SDHB, are often affected. Here we investigated the state and function of CII in RCC patients. METHODS: We evaluated tumour tissue as well as the adjacent healthy kidney tissue of 78 patients with RCC of different histotypes, focusing on their mitochondrial function. As clear cell RCC (ccRCC) is by far the most frequent histotype of RCC, we focused on these patients, which were grouped based on the pathological WHO/ISUP grading system to low- and high-grade patients, indicative of prognosis. We also evaluated mitochondrial function in organoids derived from tumour tissue of 7 patients. RESULTS: ccRCC tumours were characterized by mutated von Hippel-Lindau gene and high expression of carbonic anhydrase IX. We found low levels of mitochondrial DNA, protein and function, together with CII function in ccRCC tumour tissue, but not in other RCC types and non-tumour tissues. Mitochondrial content increased in high-grade tumours, while the function of CII remained low. Tumour organoids from ccRCC patients recapitulated molecular characteristics of RCC tissue. CONCLUSIONS: Our findings suggest that the state of CII, epitomized by its assembly and SDHB levels, deteriorates with the progressive severity of ccRCC. These observations hold the potential for stratification of patients with worse prognosis and may guide the exploration of targeted therapeutic interventions.

• MeSH
• antigeny nádorové MeSH
• dospělí MeSH
• karboanhydrasa IX metabolismus   genetika   MeSH
• karcinom z renálních buněk * patologie   metabolismus   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitochondriální DNA genetika   metabolismus   MeSH
• mitochondrie * metabolismus   patologie   genetika   MeSH
• mutace MeSH
• nádorový supresorový protein VHL genetika   metabolismus   MeSH
• nádory ledvin * patologie   metabolismus   genetika   MeSH
• respirační komplex II * metabolismus   genetika   MeSH
• senioři MeSH
• sukcinátdehydrogenasa genetika   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: This study aims to explore the lasting effects of stress experienced by pregnant women during World War II (WWII) on body and head measurements of their adult daughters. METHODS: The research sample consists of 336 female university students born in Poland between 1925 and 1951. The data include body measurements and socioeconomic information (parental occupation and number of siblings) acquired from questionnaires collected between the 1950s and 1970s. Student's t-test, Mann-Whitney test and Analysis of Variance were used to analyze differences in body measurements between groups of women born before and during the war, as well as the possible influences of socioeconomic variables. RESULTS: The mean measurements of body height, symphysion height, and waist circumference were lower in women conceived and born during the war compared to those born in the pre-war period. In contrast, the mean measurements of biacromial (shoulder) width, trunk length, and three head dimensions were higher in women conceived and born during the war. Additionally, the number of siblings appeared to be a significant factor that may have influenced the body measurements of women in both groups. For instance, a higher number of living siblings, particularly sisters, was associated with reduced body dimensions, such as body height and waist circumference, while a greater number of deceased siblings was linked to an increase in certain body dimensions. CONCLUSION: The results suggest that war-related prenatal conditions may have influenced the postnatal growth and development of women conceived and born during the war. Notably, the direction of these changes varied, which indicates that the growth response to the war-related conditions was a complex adaptation, reflecting both positive and negative changes in different body parts, rather than a uniform pattern of growth suppression.

• MeSH
• 2. světová válka * MeSH
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• psychický stres MeSH
• socioekonomické faktory MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Polsko MeSH

The alveolar-capillary interface is the key functional element of gas exchange in the human lung, and disruptions to this interface can lead to significant medical complications. However, it is currently challenging to adequately model this interface in vitro, as it requires not only the co-culture of human alveolar epithelial and endothelial cells but mainly the preparation of a biocompatible scaffold that mimics the basement membrane. This scaffold should support cell seeding from both sides, and maintain optimal cell adhesion, growth, and differentiation conditions. Our study investigates the use of polycaprolactone (PCL) nanofibers as a versatile substrate for such cell cultures, aiming to model the alveolar-capillary interface more accurately. We optimized nanofiber production parameters, utilized polyamide mesh UHELON as a mechanical support for scaffold handling, and created 3D-printed inserts for specialized co-cultures. Our findings confirm that PCL nanofibrous scaffolds are manageable and support the co-culture of diverse cell types, effectively enabling cell attachment, proliferation, and differentiation. Our research establishes a proof-of-concept model for the alveolar-capillary interface, offering significant potential for enhancing cell-based testing and advancing tissue-engineering applications that require specific nanofibrous matrices.

• MeSH
• bazální membrána MeSH
• lidé MeSH
• nanovlákna * chemie   MeSH
• ověření koncepční studie MeSH
• plicní alveoly * chemie   cytologie   MeSH
• polyestery * chemie   MeSH
• tkáňové inženýrství * metody   MeSH
• tkáňové podpůrné struktury * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

A tubular microdialysis probe is made from polysulfone hollow fibre for human haemodialysis, which has an inner diameter of 200 μm and a thickness of 20 μm. Milk is deposited to the outer surface of the hollow fibre and allowed to dry to form a dry sample. The tubular probe is then connected to the syringe pump and microdialysis of the dry sample into 0.5 mol/L HCl as acceptor is performed. 2.5 μL of microdialysate is obtained and analyzed for inorganic cations by capillary electrophoresis with contactless conductivity detection. Baseline separation of NH4+, K+, Ca2+, Na+, Mg2+, Li+ is achieved in 5.5 mol/L acetic acid as background electrolyte using a fused silica capillary with inner diameter of 25 μm and length of 31.5 cm. The reproducibility of dry sample microdialysis including CE analysis for peak area ranges from 2.4 to 3.9 % after normalization to Li+ as internal standard.

• MeSH
• elektroforéza kapilární * přístrojové vybavení   metody   MeSH
• kationty * analýza   MeSH
• mikrodialýza * přístrojové vybavení   metody   MeSH
• mléko * chemie   MeSH
• skot MeSH
• zvířata MeSH
• Check Tag
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH

BACKGROUND: Perianal fistulas of Crohn's disease (CD) create a significant burden on patients' lives. However, the efficacy and safety of adipose-derived mesenchymal stem cell treatment are contradicting, and real-world evidence is lacking. AIMS: To examine the usability of darvadstrocel therapy in managing perianal CD. METHODS: We enrolled patients with CD and perianal fistulas in this retrospective multicenter study. The primary outcome was perianal clinical remission (defined as all treated fistulas closed) at weeks 26 and 52. Secondary outcomes were clinical response rates (≥ 1 fistulas closed), perianal activity (PDAI), patient satisfaction, and adverse events. Data were recorded at baseline and weeks 12, 26 and 52. Prediction of primary outcomes was performed by logistic regression. RESULTS: Overall, among 223 patients (male/female ratio: 0.48), perianal clinical remission was achieved in 78.2% and 62.3% until weeks 26 and 52. Baseline PDAI score (OR 0.75), number of fistulas (OR 0.28) and the number of weeks after preparation for surgery (OR 0.98) were associated with treatment failure. The clinical response rates were 84.8% and 79.8% at weeks 26 and 52. Improvement of subjective perianal symptoms was achieved in 77.8% and 78.4% of patients, respectively. Adverse events occurred in 13.5% of patients; perianal abscesses and proctalgia were the most frequently reported. CONCLUSION: Effectiveness data were higher than in clinical trials. The safety profile was reassuring, and patients' satisfaction was high. Appropriate patient selection, fistula preparation and expertise may help to achieve treatment success.

• MeSH
• Crohnova nemoc * terapie   komplikace   MeSH
• dospělí MeSH
• indukce remise MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• rektální píštěl * terapie   etiologie   MeSH
• retrospektivní studie MeSH
• spokojenost pacientů MeSH
• transplantace mezenchymálních kmenových buněk * metody   škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUNDS: SWI/SNF complexes represent a family of multi-subunit chromatin remodelers that are affected by alterations in >20% of human tumors. While mutations of SWI/SNF genes are relatively uncommon in prostate cancer (PCa), the literature suggests that deregulation of various subunits plays a role in prostate tumorigenesis. To assess SWI/SNF functions in a clinical context, we studied the mutually exclusive, paralogue accessory subunits SMARCD1, SMARCD2, and SMARCD3 that are included in every known complex and are sought to confer specificity. METHODS: Performing immunohistochemistry (IHC), the protein levels of the SMARCD family members were measured using a tissue microarray (TMA) comprising malignant samples and matching healthy tissue of non-metastatic PCa patients (n = 168). Moreover, IHC was performed in castration-resistant tumors (n = 9) and lymph node metastases (n = 22). To assess their potential role as molecular biomarkers, SMARCD1 and SMARCD3 protein levels were correlated with clinical parameters such as T stage, Gleason score, biochemical recurrence, and progression-free survival. RESULTS: SMARCD1 protein levels in non-metastatic primary tumors, lymph node metastases, and castration-resistant samples were significantly higher than in benign tissues. Likewise, SMARCD3 protein expression was elevated in tumor tissue and especially lymph node metastases compared to benign samples. While SMARCD1 levels in primary tumors did not exhibit significant associations with any of the tested clinical parameters, SMARCD3 exhibited an inverse correlation with pre-operative PSA levels. Moreover, low SMARCD3 expression was associated with progression to metastasis. CONCLUSIONS: In congruence with previous literature, our results implicate that both SMARCD1 and SMARCD3 may exhibit relevant functions in the context of prostate tumorigenesis. Moreover, our approach suggests a potential role of SMARCD3 as a novel prognostic marker in clinically non-metastatic PCa.

• MeSH
• chromozomální proteiny, nehistonové * genetika   metabolismus   MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru patologie   metabolismus   genetika   MeSH
• lymfatické metastázy MeSH
• nádorové biomarkery * genetika   metabolismus   MeSH
• nádory prostaty rezistentní na kastraci patologie   genetika   metabolismus   MeSH
• nádory prostaty * patologie   metabolismus   genetika   MeSH
• prognóza MeSH
• senioři MeSH
• stupeň nádoru MeSH
• transkripční faktory genetika   metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE OF REVIEW: Upper tract urothelial carcinoma (UTUC) is a rare malignancy posing significant diagnostic and management challenges. This review provides an overview of the evidence supporting various imaging modalities and offers insights into future innovations in UTUC imaging. RECENT FINDINGS: With the growing use of advancements in computed tomography (CT) technologies for both staging and follow-up of UTUC patients, continuous innovations aim to enhance performance and minimize the risk of excessive exposure to ionizing radiation and iodinated contrast medium. In patients unable to undergo CT, magnetic resonance imaging serves as an alternative imaging modality, though its sensitivity is lower than CT. Positron emission tomography, particularly with innovative radiotracers and theranostics, has the potential to significantly advance precision medicine in UTUC. Endoscopic imaging techniques including advanced modalities seem to be promising in improved visualization and diagnostic accuracy, however, evidence remains scarce. Radiomics and radiogenomics present emerging tools for noninvasive tumor characterization and prognosis. SUMMARY: The landscape of imaging for UTUC is rapidly evolving, with significant advancements across various modalities promising improved diagnostic accuracy, patient outcomes, and safety.

• MeSH
• karcinom z přechodných buněk * diagnóza   diagnostické zobrazování   terapie   patologie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• nádory ledvin diagnostické zobrazování   terapie   diagnóza   patologie   MeSH
• nádory močovodu diagnostické zobrazování   diagnóza   terapie   patologie   MeSH
• počítačová rentgenová tomografie metody   MeSH
• pozitronová emisní tomografie metody   MeSH
• staging nádorů MeSH
• urologické nádory diagnóza   diagnostické zobrazování   terapie   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

PURPOSE: The aim of this study was to develop a simple, robust, and easy-to-use calibration procedure for correcting misalignments in rosette MRI k-space sampling, with the objective of producing images with minimal artifacts. METHODS: Quick automatic calibration scans were proposed for the beginning of the measurement to collect information on the time course of the rosette acquisition trajectory. A two-parameter model was devised to match the measured time-varying readout gradient delays and approximate the actual rosette sampling trajectory. The proposed calibration approach was implemented, and performance assessment was conducted on both phantoms and human subjects. RESULTS: The fidelity of phantom and in vivo images exhibited significant improvement compared with uncorrected rosette data. The two-parameter calibration approach also demonstrated enhanced precision and reliability, as evidenced by quantitative T2*$$ {\mathrm{T}}_2^{\ast } $$ relaxometry analyses. CONCLUSION: Adequate correction of data sampling is a crucial step in rosette MRI. The presented experimental results underscore the robustness, ease of implementation, and suitability for routine experimental use of the proposed two-parameter rosette trajectory calibration approach.

• MeSH
• algoritmy * MeSH
• artefakty * MeSH
• fantomy radiodiagnostické * MeSH
• kalibrace MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   MeSH
• mozek diagnostické zobrazování   MeSH
• počítačové zpracování obrazu * metody   MeSH
• reprodukovatelnost výsledků MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Despite the lower virulence of current SARS-CoV-2 variants and high rates of vaccinated and previously infected subjects, COVID-19 remains a persistent threat in kidney transplant recipients (KTRs). This study evaluated the parameters of anti-SARS-CoV-2 antibody production in 120 KTRs. The production of neutralizing antibodies in KTRs, following booster vaccination with the mRNA vaccine BNT162b2, was significantly decreased and their decline was faster than in healthy subjects. Factors predisposing to the downregulation of anti-SARS-CoV-2 neutralizing antibodies included age, lower estimated glomerular filtration rate, and a full dose of mycophenolate mofetil. Neutralizing antibodies correlated with those targeting the SARS-CoV-2 receptor binding domain (RBD), SARS-CoV-2 Spike trimmer, total SARS-CoV-2 S1 protein, as well as with antibodies to the deadly SARS-CoV-1 virus. No cross-reactivity was found with antibodies against seasonal coronaviruses. KTRs exhibited lower postvaccination production of neutralizing antibodies against SARS-CoV-2; however, the specificity of their humoral response did not differ compared to healthy subjects.

• MeSH
• COVID-19 * imunologie   prevence a kontrola   MeSH
• dospělí MeSH
• glykoprotein S, koronavirus imunologie   MeSH
• humorální imunita MeSH
• lidé středního věku MeSH
• lidé MeSH
• neutralizující protilátky * krev   imunologie   MeSH
• příjemce transplantátu * MeSH
• protilátky virové * krev   imunologie   MeSH
• SARS-CoV-2 * imunologie   MeSH
• sekundární imunizace MeSH
• senioři MeSH
• transplantace ledvin * škodlivé účinky   MeSH
• vakcína BNT162 imunologie   aplikace a dávkování   MeSH
• vakcíny proti COVID-19 imunologie   aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: Nonpharmacologic interventions (NPIs) constitute an important part of treatment for older adults, cover a broad and diverse range of interventions, and have advantages over pharmacologic interventions (eg, limited adverse side effects). However, an unambiguous definition of NPIs is still lacking. Defining NPIs may facilitate research on this topic and enhance comparability of results between studies, and might help to face the challenges of recognition, acceptation, funding, and implementation. Therefore, the aim of this review was to provide an overview and comparison of the definitions of NPIs used in the current literature on older adults. DESIGN: A systematic review was performed to provide an overview of the definitions of NPIs that are used in the current literature on older populations and to organize the characteristics involved in the definitions. SETTING AND PARTICIPANTS: People ≥60 years of age were included, not limited to a specific setting. METHODS: A systematic search was performed in the following 5 databases: PubMed, Embase, Clarivate Analytics/Web of Science Core Collection, Cumulative Index to Nursing and Allied Health Literature, and Wiley/Cochrane Library. The time frame within the databases was from inception to December 4, 2023. Review articles, editorials and consensus papers were included. RESULTS: We included 28 articles. We organized the definitions of NPI according to 4 different aspects: types of interventions involved, target population, goals the interventions addressed, and requirements of the interventions. Definitions in the current literature can generally be divided into 2 groups: NPIs described as not involving medication, and more elaborated multidomain definitions. Based on the results, we formulated criteria for types of interventions that can be considered an NPI. CONCLUSIONS AND IMPLICATIONS: Using current descriptions and characteristics, elements for a new definition for NPIs were proposed. To improve research in this field, consensus needs to be reached regarding elements covered by a definition of NPIs.

• MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• terapie * metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• systematický přehled MeSH

BACKGROUND: Auer rods (AuRs) are prominent intracellular structures found almost exclusively in myeloid cell malignancies, such as acute myeloid leukemia (AML), chronic and juvenile myelomonocytic leukemia and myelodysplastic syndrome. Extremely rare AuRs have been reported in patients with acute lymphoblastic leukemia (ALL) or among ambiguous lineage leukemia patients with a dominantly lymphoblastic immunophenotype. PROCEDURE: We report diagnostic and follow-up data of an international cohort of 11 children suffering from leukemias with AuRs and with significant presence of T and myeloid markers, majority of whom categorized as early T-cell precursor (ETP, n = 7); or T-ALL (ETP status unknown, n = 2), ALAL (acute leukemia of ambiguous lineage, n = 1), and AML reclassified from ALAL (n = 1). We described other diagnostic details and treatment types and responses. Moreover, we summarize previously published data. RESULTS: Among the four patients who started and remained on ALL-type therapy, all were in the first complete remission, whereas both patients who started and remained on AML-type therapy relapsed and died. Of the patients who followed either a combined ALL/AML protocol (Interfant 06) or who switched from one of the two types of therapy to the other, one patient died, and the remaining four were in first complete remission at the most recent follow-up. We also searched for similar cases in the literature and found only three additional children with nonmyeloid leukemia and AuRs and 10 adults with this type of leukemia. CONCLUSIONS: Briefly, ALL- or combined ALL/AML-type therapy may be effective for treating AuR-positive leukemia patients with a lymphoid immunophenotype.

• MeSH
• akutní lymfatická leukemie patologie   terapie   imunologie   MeSH
• akutní myeloidní leukemie patologie   terapie   imunologie   MeSH
• dítě MeSH
• imunofenotypizace * MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• následné studie MeSH
• předškolní dítě MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články 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
• autologní transplantace MeSH
• dospělí MeSH
• lenalidomid aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom * diagnóza   mortalita   terapie   patologie   MeSH
• prognóza MeSH
• průtoková cytometrie * metody   MeSH
• retrospektivní studie MeSH
• reziduální nádor * diagnóza   MeSH
• senioři MeSH
• staging nádorů MeSH
• transplantace hematopoetických kmenových buněk metody   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Pegunigalsidase alfa, a PEGylated α-galactosidase A enzyme replacement therapy (ERT) for Fabry disease, has a longer plasma half-life than other ERTs administered intravenously every 2 weeks (E2W). BRIGHT (NCT03180840) was a phase III, open-label study in adults with Fabry disease, previously treated with agalsidase alfa or beta E2W for ≥3 years, who switched to 2 mg/kg pegunigalsidase alfa every 4 weeks (E4W) for 52 weeks. Primary objective assessed safety, including number of treatment-emergent adverse events (TEAEs). Thirty patients were enrolled (24 males); 23 previously received agalsidase beta. Pegunigalsidase alfa plasma concentrations remained above the lower limit of quantification throughout the 4-week dosing interval. Thirty-three of 182 TEAEs (in 9 patients) were considered treatment-related; all were mild/moderate. No patients developed de novo anti-drug antibodies (ADAs). In the efficacy analysis (n = 29), median (inter-quartile range) eGFR change from baseline over 52 weeks was -1.9 (-5.9; 1.8) mL/min/1.73 m2 (n = 28; males [n = 22]: -2.4 [-5.2; 3.2]; females [n = 6]: -0.7 [-9.2; 2.0]). Overall, median eGFR slope was -1.9 (-8.3; 1.9) mL/min/1.73 m2/year (ADA-negative [n = 20]: -1.2 [-6.4; 2.6]; ADA-positive [n = 9]: -8.4 [-11.6; -1.0]). Lyso-Gb3 concentrations were low and stable in females, with a slight increase in males (9/24 ADA-positive). The BRIGHT study results suggest that 2 mg/kg pegunigalsidase alfa E4W is tolerated well in stable adult patients with Fabry disease. Due to the low number of patients in this study, more research is needed to demonstrate the effects of pegunigalsidase alfa given E4W. Further evidence, outside of this clinical trial, should be factored in for physicians to prolong the biweekly ERT intervals to E4W. TAKE-HOME MESSAGE: Treatment with 2 mg/kg pegunigalsidase alfa every 4 weeks could offer a new treatment option for patients with Fabry disease.

• MeSH
• alfa-galaktosidasa * aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• enzymová substituční terapie * metody   MeSH
• Fabryho nemoc * farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• polyethylenglykoly aplikace a dávkování   MeSH
• rekombinantní proteiny * aplikace a dávkování   terapeutické užití   MeSH
• rozvrh dávkování léků MeSH
• senioři MeSH
• sfingolipidy krev   MeSH
• trihexosylceramidy krev   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

AIM: A diabetes-related foot ulcer (DFU) is a major risk factor for lower-extremity amputation (LEA). To help clinicians predict the risk of LEA in people with DFU, the Diabetic Foot Risk Assessment (DIAFORA) system was developed but has never been externally validated. METHODS: In this study, 317 people presenting with a new DFU were included. At baseline, participants were grouped into three groups based on their DIAFORA score: low-risk (<15), medium-risk (15-25), and high-risk (>25). Participants were followed until healing, LEA, death, or at least 3 months. Discriminative accuracy was evaluated using sensitivity, specificity, likelihood ratios (LRs) and the area under the curve (AUC). RESULTS: All 317 participants completed at least 3 months of follow-up for a median duration of 146 days, during which 12.6% underwent minor amputation and 2.5% major amputation. People in the low- and medium-risk categories had major amputation rates of 0.9% and 2.1%, respectively, and negative LR of major LEA of 0.10 and 0.38, respectively, while the people in the high-risk category had an amputation rate of 25.0% and a positive LR of 12.9. The DIAFORA risk groups had a sensitivity of 75.0% and a specificity of 65.7%, with a corresponding AUC of 0.78 (95% CI 0.68-0.87) for the prediction of major LEA. CONCLUSION: The DIAFORA score is a useful tool for risk stratification of people presenting with a newly occurred DFU, with the external validation presenting results similar to those presented in the original study. The DIAFORA score may guide clinicians towards more individualized DFU treatment regimens.

• MeSH
• amputace * statistika a číselné údaje   MeSH
• diabetická noha * chirurgie   epidemiologie   MeSH
• dolní končetina chirurgie   MeSH
• hodnocení rizik metody   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• prediktivní hodnota testů MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• validační studie MeSH
• Geografické názvy
• Dánsko MeSH

BACKGROUND: The medication used to treat benign prostate hyperplasia (BPH), a common condition in men over 50 years of age, can alter the levels of biomarkers used in prostate cancer detection. Commonly used medications for BPH include alpha-blockers, 5-alpha reductase inhibitors (5-ARIs), and muscarinic antagonists. We studied the impact of these drugs on total prostate-specific antigen (tPSA), free PSA (fPSA), [-2]proPSA, fPSA/tPSA ratio, and the Prostate Health Index (PHI), as well as novel potential biomarkers in the form of glycan composition of fPSA. PATIENTS AND METHODS: Serum samples were collected from 564 males with BPH, with a mean age of 68.5 years. The samples were used to measure levels of tPSA, fPSA, and [-2]proPSA. The fPSA/tPSA and PHI were then calculated. The glycan composition of fPSA was analyzed using lectin-based glycoprofiling. Pharmacotherapy data was collected from the patients' medical records. RESULTS: Alpha-blocker monotherapy was associated with higher fPSA and fPSA/tPSA ratio, and decreased PHI. Levels of tPSA were not impacted. Alpha-blocker and 5-ARI dual therapy was associated with reduced levels of fPSA, [-2]proPSA, and PHI. Therapy combining alpha-blockers and antimuscarinic agents did not significantly influence biomarker levels apart from an increase in a Maackia amurensis lectin-recognized glycan originating in fPSA. CONCLUSION: BPH pharmacotherapy notably affects prostate cancer biomarkers. Recognizing the impact of pharmacotherapy is crucial for achieving an accurate diagnosis of prostate cancer and for planning treatment.

• MeSH
• alfa blokátory terapeutické užití   MeSH
• antagonisté muskarinových receptorů * terapeutické užití   MeSH
• glykosylace MeSH
• hyperplazie prostaty * krev   farmakoterapie   MeSH
• inhibitory 5-alfa-reduktasy terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prostaty krev   farmakoterapie   MeSH
• prostata patologie   metabolismus   MeSH
• prostatický specifický antigen * krev   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with patients having unresectable or metastatic disease at diagnosis, with poor prognosis and very short survival. Given that genetic variation within autophagy-related genes influences autophagic flux and susceptibility to solid cancers, we decided to investigate whether 55,583 single nucleotide polymorphisms (SNPs) within 234 autophagy-related genes could influence the risk of developing PDAC in three large independent cohorts of European ancestry including 12,754 PDAC cases and 324,926 controls. The meta-analysis of these populations identified, for the first time, the association of the BIDrs9604789 variant with an increased risk of developing the disease (ORMeta = 1.31, p = 9.67 × 10-6). We also confirmed the association of TP63rs1515496 and TP63rs35389543 variants with PDAC risk (OR = 0.89, p = 6.27 × 10-8 and OR = 1.16, p = 2.74 × 10-5). Although it is known that BID induces autophagy and TP63 promotes cell growth, cell motility and invasion, we also found that carriers of the TP63rs1515496G allele had increased numbers of FOXP3+ Helios+ T regulatory cells and CD45RA+ T regulatory cells (p = 7.67 × 10-4 and p = 1.56 × 10-3), but also decreased levels of CD4+ T regulatory cells (p = 7.86 × 10-4). These results were in agreement with research suggesting that the TP63rs1515496 variant alters binding sites for FOXA1 and CTCF, which are transcription factors involved in modulating specific subsets of regulatory T cells. In conclusion, this study identifies BID as new susceptibility locus for PDAC and confirms previous studies suggesting that the TP63 gene is involved in the development of PDAC. This study also suggests new pathogenic mechanisms of the TP63 locus in PDAC.

• MeSH
• autofagie * genetika   MeSH
• běloši genetika   MeSH
• duktální karcinom pankreatu * genetika   patologie   MeSH
• forkhead transkripční faktory MeSH
• genetická predispozice k nemoci * MeSH
• hepatocytární jaderný faktor 3-alfa genetika   metabolismus   MeSH
• jednonukleotidový polymorfismus * MeSH
• kohortové studie MeSH
• lidé MeSH
• nádorové biomarkery * genetika   MeSH
• nádorové supresorové proteiny * genetika   MeSH
• nádory slinivky břišní * genetika   patologie   MeSH
• studie případů a kontrol MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH