OBJECTIVES: To develop a gadolinium-free MRI-based diagnosis prediction decision tree (DPDT) for adult-type diffuse gliomas and to assess the added value of gadolinium-based contrast agent (GBCA) enhanced images. MATERIALS AND METHODS: This study included preoperative grade 2-4 adult-type diffuse gliomas (World Health Organization 2021) scanned between 2010 and 2021. The DPDT, incorporating eleven GBCA-free MRI features, was developed using 18% of the dataset based on consensus readings. Diagnosis predictions involved grade (grade 2 vs. grade 3/4) and molecular status (isocitrate dehydrogenase (IDH) and 1p/19q). GBCA-free diagnosis was predicted using DPDT, while GBCA-enhanced diagnosis included post-contrast images. The accuracy of these predictions was assessed by three raters with varying experience levels in neuroradiology using the test dataset. Agreement analyses were applied to evaluate the prediction performance/reproducibility. RESULTS: The test dataset included 303 patients (age (SD): 56.7 (14.2) years, female/male: 114/189, low-grade/high-grade: 54/249, IDH-mutant/wildtype: 82/221, 1p/19q-codeleted/intact: 34/269). Per-rater GBCA-free predictions achieved ≥ 0.85 (95%-CI: 0.80-0.88) accuracy for grade and ≥ 0.75 (95%-CI: 0.70-0.80) for molecular status, while GBCA-enhanced predictions reached ≥ 0.87 (95%-CI: 0.82-0.90) and ≥ 0.77 (95%-CI: 0.71-0.81), respectively. No accuracy difference was observed between GBCA-free and GBCA-enhanced predictions. Group inter-rater agreement was moderate for GBCA-free (0.56 (95%-CI: 0.46-0.66)) and substantial for GBCA-enhanced grade prediction (0.68 (95%-CI: 0.58-0.78), p = 0.008), while substantial for both GBCA-free (0.75 (95%-CI: 0.69-0.80) and GBCA-enhanced (0.77 (95%-CI: 0.71-0.82), p = 0.51) molecular status predictions. CONCLUSION: The proposed GBCA-free diagnosis prediction decision tree performed well, with GBCA-enhanced images adding little to the preoperative diagnostic accuracy of adult-type diffuse gliomas. KEY POINTS: Question Given health and environmental concerns, is there a gadolinium-free imaging protocol to preoperatively evaluate gliomas comparable to the gadolinium-enhanced standard practice? Findings The proposed gadolinium-free diagnosis prediction decision tree for adult-type diffuse gliomas performed well, and gadolinium-enhanced MRI demonstrated only limited improvement in diagnostic accuracy. Clinical relevance Even inexperienced raters effectively classified adult-type diffuse gliomas using the gadolinium-free diagnosis prediction decision tree, which, until further validation, can be used alongside gadolinium-enhanced images to respect standard practice, despite this study showing that gadolinium-enhanced images hardly improved diagnostic accuracy.

• MeSH
• dospělí MeSH
• gadolinium MeSH
• gliom * diagnostické zobrazování   MeSH
• kontrastní látky * MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   MeSH
• nádory mozku * diagnostické zobrazování   MeSH
• prediktivní hodnota testů MeSH
• reprodukovatelnost výsledků MeSH
• rozhodovací stromy * MeSH
• senioři MeSH
• stupeň nádoru * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Aveir DR (Abbott, Abbott Park, IL) is a dual-chamber leadless pacemaker (LP) system with distinct atrial and ventricular LPs (ALP, VLP) that communicate wirelessly to deliver atrioventricular synchronous pacing. Success rates of these implant-to-implant (i2i) transmissions have not been systematically evaluated. OBJECTIVE: This study aims to evaluate chronic i2i success rates in a clinical setting. METHODS: Patients meeting standard dual-chamber pacing indications were enrolled and implanted with dual-chamber LP systems as part of a prospective international clinical trial (Aveir DR i2i Study). The percent of successful i2i transmissions from ALP-to-VLP (A-to-V) and VLP-to-ALP (V-to-A) were interrogated from LPs in de novo patients using the device programmer at implant, discharge, and at 1, 3, and 6 months postimplant (1M, 3M, 6M). RESULTS: A total of 399 patients completed device implant and i2i diagnostic interrogation (62% male; age 69 years; 65% sinus node dysfunction, 32% atrioventricular [AV] block). Median A-to-V and V-to-A i2i success rates exceeded 90% of beats at all time-points from implant to 6M. The minority of patients with A-to-V or V-to-A i2i success in <70% of beats at implant (A-to-V: 19% of patients, V-to-A: 31% of patients) showed roughly 40% improvement by 1M, with this minority dropping to roughly 5% of patients by 6M. Improvement in i2i communication success may be attributed to reprogramming of i2i setting levels, natural changes in dominant posture, and device stabilization. CONCLUSION: Wireless implant-to-implant communication in the new dual-chamber leadless pacemaker system demonstrated successful transmissions in >90% of beats throughout the 6-month evaluation period. Communication success improved significantly over time postimplant for specific subgroups. CLINICAL TRIAL REGISTRATION: Aveir DR i2i Study, ClinicalTrials.gov ID NCT05252702.

• MeSH
• bezdrátová technologie MeSH
• design vybavení * MeSH
• kardiostimulace umělá metody   MeSH
• kardiostimulátor * MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• prospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

RESPONSE/RECOMMENDATION: The use of surgical drains in routine primary total knee and total hip arthroplasty is not recommended. LEVEL OF EVIDENCE: High. EXPERT VOTING: Agree 83.52%, Disagree 12.91%, Abstain 3.59%.

• MeSH
• drenáž * přístrojové vybavení   MeSH
• lidé MeSH
• náhrada kyčelního kloubu * MeSH
• totální endoprotéza kolene * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• dopisy MeSH
• přehledy MeSH

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of intravenous (IV) secukinumab in patients with active psoriatic arthritis (PsA). METHODS: INVIGORATE-2 (NCT04209205) was a randomized, placebo-controlled, phase 3 trial. Patients with active PsA were randomized 1:1 to receive IV secukinumab (6 mg/kg at baseline followed by 3 mg/kg every four weeks [q4w]) or placebo. At week 16, patients randomized to placebo were switched to IV secukinumab (3 mg/kg q4w), and patients who received IV secukinumab continued treatment through week 52. The primary efficacy endpoint was achievement of 50% improvement in American College of Rheumatology response criteria (ACR50) at week 16. Efficacy and safety were evaluated through weeks 52 and 60, respectively. RESULTS: Among 191 patients randomized to IV secukinumab and 190 to placebo/IV secukinumab, 177 (92.7%) and 170 (89.5%) completed the entire study period, respectively. A significantly higher proportion of patients who received IV secukinumab versus placebo achieved ACR50 at week 16 (31.4% vs 6.3%; adjusted P < 0.0001). All secondary efficacy endpoints were met at week 16 (all adjusted P < 0.05 using the predefined hypothesis-testing hierarchy). Patients who switched from placebo to secukinumab at week 16 showed rapid improvements in ACR50 rates; by week 52, both treatment arms experienced similar improvements in efficacy outcomes. No new or unexpected safety signals were observed with receiving IV secukinumab. One death was reported in the placebo group before week 16. CONCLUSION: IV secukinumab led to rapid and sustained improvements in clinical measures of PsA, and the safety profile was consistent with that of secukinumab administered subcutaneously.

• MeSH
• antirevmatika terapeutické užití   aplikace a dávkování   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• humanizované monoklonální protilátky * aplikace a dávkování   terapeutické užití   MeSH
• intravenózní podání MeSH
• lidé středního věku MeSH
• lidé MeSH
• psoriatická artritida * farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie 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

Mismatch repair-deficient (dMMR) endometrial cancer (EC) is an inflamed phenotype with poor outcomes when meeting high-risk criteria and limited treatment options in the adjuvant setting. We report protocol-prespecified subgroup analysis of patients with dMMR tumors from the phase III ENGOT-en11/GOG-3053/KEYNOTE-B21 study (ClinicalTrials.gov identifier: NCT04634877) in newly diagnosed, high-risk EC after surgery with curative intent. Patients were randomly assigned to pembrolizumab 200 mg or placebo (six cycles) plus carboplatin-paclitaxel (four to six cycles) once every 3 weeks, then pembrolizumab 400 mg or placebo once every 6 weeks (six cycles), respectively. MMR status was a stratification factor. Patients received radiotherapy at investigator discretion. Investigator-assessed disease-free survival (DFS) was a primary end point. No formal hypothesis testing was performed for subgroup analysis. In the intention-to-treat population, 141 patients in the pembrolizumab arm and 140 in the placebo arm had dMMR tumors. At this interim analysis, hazard ratio for DFS favored pembrolizumab (0.31 [95% CI, 0.14 to 0.69]); median DFS was not reached in either group. Two-year DFS rates were 92.4% (95% CI, 84.4 to 96.4) and 80.2% (95% CI, 70.8 to 86.9), respectively. No new safety signals occurred. Longer-term follow-up of outcomes will be evaluated at final analysis. Preplanned subgroup analysis on the basis of the study's stratification factors suggests that pembrolizumab plus chemotherapy improves DFS and is clinically relevant for patients with dMMR tumors in the curative-intent setting.

• MeSH
• adjuvantní chemoterapie MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• humanizované monoklonální protilátky * terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• karboplatina aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory endometria * patologie   farmakoterapie   mortalita   terapie   MeSH
• oprava chybného párování bází DNA * MeSH
• paclitaxel * aplikace a dávkování   MeSH
• přežití bez známek nemoci MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

Around 180 genes have been associated with congenital anomalies of the kidney and urinary tract (CAKUT) in mice, and represent promising novel candidate genes for human CAKUT. In whole-exome sequencing data of two siblings with genetically unresolved multicystic dysplastic kidneys (MCDK), prioritizing variants in murine CAKUT-associated genes yielded a rare variant in the teashirt zinc finger homeobox 3 (TSHZ3) gene. Therefore, the role of TSHZ3 in human CAKUT was assessed. Twelve CAKUT patients from 9/301 (3%) families carried five different rare heterozygous TSHZ3 missense variants predicted to be deleterious. CAKUT patients with versus without TSHZ3 variants were more likely to present with hydronephrosis, hydroureter, ureteropelvic junction obstruction, MCDK, and with genital anomalies, developmental delay, overlapping with the previously described phenotypes in Tshz3-mutant mice and patients with heterozygous 19q12-q13.11 deletions encompassing the TSHZ3 locus. Comparable with Tshz3-mutant mice, the smooth muscle layer was disorganized in the renal pelvis and thinner in the proximal ureter of the nephrectomy specimen of a TSHZ3 variant carrier compared to controls. TSHZ3 was expressed in the human fetal kidney, and strongly at embryonic day 11.5-14.5 in mesenchymal compartments of the murine ureter, kidney, and bladder. TSHZ3 variants in a 5' region were more frequent in CAKUT patients than in gnomAD samples (p < 0.001). Mutant TSHZ3 harboring N-terminal variants showed significantly altered SOX9 and/or myocardin binding, possibly adversely affecting smooth muscle differentiation. Our results provide evidence that heterozygous TSHZ3 variants are associated with human CAKUT, particularly MCDK, hydronephrosis, and hydroureter, and, inconsistently, with specific extrarenal features, including genital anomalies.

• MeSH
• dítě MeSH
• heterozygot * MeSH
• homeodoménové proteiny genetika   MeSH
• kojenec MeSH
• ledviny abnormality   metabolismus   MeSH
• lidé MeSH
• missense mutace MeSH
• močové ústrojí abnormality   metabolismus   MeSH
• multicystické dysplastické ledviny genetika   MeSH
• myši MeSH
• předškolní dítě MeSH
• transkripční faktory genetika   MeSH
• urogenitální abnormality genetika   patologie   MeSH
• vezikoureterální reflux MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: The study objectives were (i) to explore the agreement between the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and physical examination in assessing enthesitis in patients with spondyloarthritis (SpA) and (ii) to investigate the prevalence and clinical relevance of subclinical enthesitis in this population. METHODS: Twenty rheumatology centers participated in this cross-sectional study. Patients with SpA, including axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), underwent both ultrasound scan and physical examination of large lower limb entheses. The OMERACT ultrasound lesions of enthesitis were considered, along with a recently proposed definition for "active enthesitis" by our group. Subclinical enthesitis was defined as the presence of "active enthesitis" in ≥1 enthesis in patients with SpA without clinical enthesitis (ie, number of positive entheses on physical examination and Leeds Enthesitis Index score = 0). RESULTS: A total of 4,130 entheses in 413 patients with SpA (224 with axSpA and 189 with PsA) were evaluated through ultrasound and physical examination. Agreement between ultrasound and physical examination ranged from moderate (ie, enthesophytes) to almost perfect (ie, power Doppler and "active enthesitis"). Patellar tendon entheses demonstrated the highest agreement, whereas Achilles tendon insertion showed the lowest. Among 158 (38.3%) of 413 patients with SpA with clinical enthesitis, 108 (68.4%) exhibited no "active enthesitis" on ultrasound. Conversely, of those 255 without clinical enthesitis, 39 (15.3%) showed subclinical enthesitis. Subclinical enthesitis was strongly associated with local structural damage. However, no differences were observed regarding the demographic and clinical profiles of patients with SpA with and without subclinical enthesitis. CONCLUSION: Our study underscores the need for a comprehensive tool integrating ultrasound and physical examination for assessing enthesitis in patients with SpA.

• MeSH
• Achillova šlacha diagnostické zobrazování   MeSH
• axiální spondyloartritida diagnostické zobrazování   MeSH
• dospělí MeSH
• entezopatie * diagnostické zobrazování   MeSH
• fyzikální vyšetření * MeSH
• lidé středního věku MeSH
• lidé MeSH
• průřezové studie MeSH
• psoriatická artritida diagnostické zobrazování   komplikace   MeSH
• spondylartritida * diagnostické zobrazování   komplikace   MeSH
• ultrasonografie * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH