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
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
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
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
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
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.
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
