Juxtaglomerular cell tumor (JxGCT) is a rare type of renal neoplasm demonstrating morphologic overlap with some mesenchymal tumors such as glomus tumor (GT) and solitary fibrous tumor (SFT). Its oncogenic drivers remain elusive, and only a few cases have been analyzed with modern molecular techniques. In prior studies, loss of chromosomes 9 and 11 appeared to be recurrent. Recently, whole-genome analysis identified alterations involving genes of MAPK-RAS pathway in a subset, but no major pathogenic alterations have been discovered in prior whole transcriptome analyses. Considering the limited understanding of the molecular features of JxGCTs, we sought to assess a collaborative series with a multiomic approach to further define the molecular characteristics of this entity. Fifteen tumors morphologically compatible with JxGCTs were evaluated using immunohistochemistry for renin, single-nucleotide polymorphism array (SNP), low-pass whole-genome sequencing, and RNA sequencing (fusion assay). In addition, methylation analysis comparing JxGCT, GT, and SFT was performed. All cases tested with renin (n=11) showed positive staining. Multiple chromosomal abnormalities were identified in all cases analyzed (n=8), with gains of chromosomes 1p, 10, 17, and 19 and losses of chromosomes 9, 11, and 21 being recurrent. A pathogenic HRAS mutation was identified in one case as part of the SNP array analysis. Thirteen tumors were analyzed by RNA sequencing, with 2 revealing in-frame gene fusions: TFG::GPR128 (interpreted as stochastic) and NAB2::STAT6 . The latter, originally diagnosed as JxGCT, was reclassified as SFT and excluded from the series. No fusions were detected in the remaining 11 cases; of note, no case harbored NOTCH fusions previously described in GT. Genomic methylation analysis showed that JxGCT, GT, and SFT form separate clusters, confirming that JxGCT represents a distinct entity (ie, different from GT). The results of our study show that JxGCTs are a distinct tumor type with a recurrent pattern of chromosomal imbalances that may play a role in oncogenesis, with MAPK-RAS pathway activation being likely a driver in a relatively small subset.

• MeSH
• dospělí MeSH
• epigeneze genetická MeSH
• epigenomika MeSH
• fúze genů * MeSH
• genetická predispozice k nemoci MeSH
• genomika MeSH
• imunohistochemie MeSH
• jednonukleotidový polymorfismus MeSH
• juxtaglomerulární aparát patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA MeSH
• nádorové biomarkery * genetika   MeSH
• nádory ledvin * genetika   patologie   chemie   MeSH
• sekvenování celého genomu MeSH
• senioři 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

Microbiology reference laboratories perform a crucial role within public health systems. This role was especially evident during the COVID-19 pandemic. In this Viewpoint, we emphasise the importance of microbiology reference laboratories and highlight the types of digital data and expertise they provide, which benefit national and international public health. We also highlight the value of surveillance initiatives among collaborative international partners, who work together to share, analyse, and interpret data, and then disseminate their findings in a timely manner. Microbiology reference laboratories have substantial impact at regional, national, and international levels, and sustained support for these laboratories is essential for public health in both pandemic and non-pandemic times.

• MeSH
• COVID-19 * epidemiologie   MeSH
• infekční nemoci MeSH
• laboratoře * ekonomika   MeSH
• lidé MeSH
• mikrobiologie MeSH
• pandemie MeSH
• SARS-CoV-2 MeSH
• veřejné zdravotnictví MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Clinical trials in oncology are important tools to identify and establish new effective drugs for cancer treatment. Since the development of the concept of precision oncology, a huge number of multi-centric biomarker-driven clinical trials have been performed and promoted by either academic institutions or pharmaceutical companies. In this scenario, the role of pathologists is essential in multiple aspects, with new challenges that should be addressed. In this position paper of the European Society of Pathology, the role of pathologists as contributors to the design of the clinical trial, as local collaborators, or as members of central review laboratories is discussed. Moreover, the paper emphasizes the important role of pathologists in guiding methods and criteria of tissue biomarker testing in the biomarker-driven clinical trials. The paper also addresses issues regarding quality control, training, and the possible role of digital pathology.

• MeSH
• klinické zkoušky jako téma * MeSH
• laboratorní medicína normy   metody   MeSH
• lidé MeSH
• nádorové biomarkery * analýza   MeSH
• nádory * patologie   farmakoterapie   MeSH
• patologové * MeSH
• společnosti lékařské MeSH
• výzkumný projekt normy   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Evropa 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

PURPOSE: The presence of MYC and BCL2 translocations (ie, double-hit lymphoma, DHL) in large B-cell lymphoma (LBCL) is associated with reduced chemosensitivity, but less is known on its impact on radiotherapy (RT) efficacy. METHODS AND MATERIALS: Patients with LBCL who received their first course of RT for relapsed/refractory disease between 2008 and 2020 were eligible if there was adequate pathologic evaluation to be categorized as DHL versus non-DHL as per the World Health Organization (fifth edition). Separate analyses were conducted by treatment intent. Predictors for response (complete and partial) and local recurrence (LR) were evaluated using Cox regression analysis. LR analysis was restricted to curative-intent patients to ensure adequate follow-up. RESULTS: Three hundred and eighty-three patients (102 DHL, 281 non-DHL, and 44% curative) were treated at 447 sites. Median time from diagnosis to RT was 11.6 months, with 38.7% of patients having primary chemorefractory disease, 37.4% having received >2 lines of systemic therapy, and 24% status post-stem cell transplant. Median biological equivalent dose (alpha/beta: 10) was 28 Gy (range: 3.2-60.0) for palliative and 46.9 Gy (range: 6.4-84.0) for curative-intent patients. With a median follow-up of 41.1 and 41.5 months among curative and palliative patients, respectively, the response was high (81.1% curative, 60.1% palliative). On univariate analysis, DHL pathology was not associated with RT response in either curative or palliative patients. Among curative patients, 2-year LR rate was 38.8%. On multivariable analysis, DHL pathology was associated with a 2 times higher risk of LR (95% CI: 1.05-3.67, P = .03), with a crude LR rate of 42.9% (DHL) versus 28.9% (non-DHL). RT was well tolerated with low rates of grade 3 or higher acute toxicity (1.8% curative, 2.9% palliative). CONCLUSIONS: Relapsed/refractory LBCL remains radioresponsive with a 60%-80% response rate to RT. Although DHL pathology does not appear to influence RT response, its presence is associated with higher rates of LR, suggesting that it may be more radioresistant.

• MeSH
• difúzní velkobuněčný B-lymfom * radioterapie   patologie   genetika   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru * patologie   MeSH
• mladý dospělý MeSH
• protoonkogenní proteiny c-bcl-2 genetika   MeSH
• protoonkogenní proteiny c-myc genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• translokace genetická MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

The lymphatic pathway is an important route of metastasis in gynecological malignancy. Therefore, the examination of lymph nodes is an essential part of the ultrasound evaluation in patients with known or suspected gynecological malignancy. The lymph nodes most frequently involved in gynecological malignancy (apart from vulvar cancer) are parietal (retroperitoneal) and visceral abdominopelvic lymph nodes. In advanced disease, more distant lymph-node regions, such as the inguinal, axillary and supraclavicular lymph nodes, can also be involved. The standardized description of lymph nodes has been published previously by the Vulvar International Tumor Analysis (VITA) collaborative group. Herein, a collaborative group of gynecologists and gynecological oncologists with extensive ultrasound experience presents a systematic methodology for ultrasonographic lymph-node assessment performed as part of the locoregional and distant work-up to assess the extent of gynecological malignancy. The aim of this consensus opinion is also to describe the anatomical classification and drainage pathways of the lymphatic system as relevant to the gynecological organs. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

• MeSH
• konsensus * MeSH
• lidé MeSH
• lymfatické metastázy * diagnostické zobrazování   MeSH
• lymfatické uzliny * diagnostické zobrazování   patologie   MeSH
• nádory ženských pohlavních orgánů * diagnostické zobrazování   patologie   MeSH
• staging nádorů * MeSH
• terminologie jako téma MeSH
• ultrasonografie * metody   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Initiation of newborn screening (NBS) programs in Europe dates back to the 1960s. One of the most recent expansions of NBS programs was the addition of severe combined immunodeficiency (SCID) based on detection of T-cell receptor excision circles (TRECs). In this review, we present an overview of the current situation in Europe. To avoid a biased overview based on only published results, a 37-item survey on TREC-based NBS was sent to representatives of 46 European countries. With a response rate of 83%, we collected data of 38 countries. Seventeen of the 38 European countries that have completed the survey have nationally or regionally implemented TREC-based NBS. The survey results emphasize similarities and differences as well as common practices and challenges in TREC-based NBS. Because TRECs are a general surrogate marker for severe T lymphocytopenia, conditions other than SCID are also identified. Therefore, the initial definition of the target disease as "SCID" might need to be reconsidered and extended to "SCID and severe T lymphocytopenia." Even though complete harmonization of TREC-based NBS programs across Europe will remain challenging, collaboration and close partnerships will help in the move toward universal TREC-based screening for all newborns, resulting in more infants with SCID and severe T lymphocytopenia being detected each year.

• MeSH
• lidé MeSH
• lymfopenie * imunologie   diagnóza   MeSH
• novorozenec MeSH
• novorozenecký screening * MeSH
• receptory antigenů T-buněk * genetika   imunologie   MeSH
• těžká kombinovaná imunodeficience * diagnóza   epidemiologie   imunologie   MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Evropa MeSH

A standardized methodology for the ultrasound evaluation of the pelvic sidewall has not been proposed to date. Herein, a collaborative group of gynecologists and gynecological oncologists with extensive ultrasound experience presents a systematic methodology for the ultrasonographic evaluation of structures within the pelvic sidewall. Five categories of anatomical structures are described (muscles, vessels, lymph nodes, nerves and ureters). A step-by-step transvaginal ultrasound (or, when this is not feasible, transrectal ultrasound) approach is outlined for the evaluation of each anatomical landmark within these categories. Accurate assessment of the pelvic sidewall using a standardized approach improves the detection and diagnosis of non-gynecological pathologies that may mimic gynecological tumors, reducing the risk of unnecessary and even harmful intervention. Furthermore, it plays an important role in completing the staging of malignant gynecological conditions. Transvaginal or transrectal ultrasound therefore represents a viable alternative to magnetic resonance imaging in the preoperative evaluation of lesions affecting the pelvic sidewall, if performed by an expert sonographer. A series of videoclips showing normal and abnormal findings within each respective category illustrates how establishing a universally applicable approach for evaluating this crucial region will be helpful for assessing both benign and malignant conditions affecting the pelvic sidewall. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

• MeSH
• konsensus * MeSH
• lidé MeSH
• lymfatické uzliny diagnostické zobrazování   MeSH
• pánev * diagnostické zobrazování   MeSH
• ultrasonografie * metody   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Current trends in the addiction field reflect a significant emphasis on the workforce development and education. There are already some data about university-based addiction studies programs, but not much from Australasia. METHODS: The aim is to provide an overview and describe the academic programs for addiction professionals in Australia and Aotearoa NZ. The research was conducted in 2017 and updated in 2023. Firstly, university websites were searched using pre-defined keywords, followed by a content analysis of the identified programs. The data were analysed and interpreted by using descriptive statistics. RESULTS: We found 21 universities in Australia (13) and Aotearoa NZ (8) where 46 single programs are provided. There are three bachelor programs, nine masters, and the majority of degrees include (post)graduate certificates and diplomas. No doctorate programs are identified. The taught courses provide comprehensive coverage of the addiction field topics. Twelve programs state clearly that there is clinical practice/internship included. Application to most programs requires completion of a relevant degree and in some cases possible clinical experience. DISCUSSION AND CONCLUSIONS: In comparison to educational options in other regions, we observe a trend towards preparing university graduates for the workforce, thereby expanding the range of programs at lower levels. Most programs possibly represent clinically oriented education primarily specialising in addictions, and graduate programs in addictions for professionals with other disciplinary bases. Great emphasis is given to the quality standards of education, and also to relationship between education and labour market. Findings help opening opportunities to collaborate globally.

• MeSH
• lidé MeSH
• návykové chování epidemiologie   MeSH
• poruchy spojené s užíváním psychoaktivních látek * epidemiologie   MeSH
• univerzity MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Austrálie MeSH
• Nový Zéland MeSH

BACKGROUND AND OBJECTIVE: Biparametric magnetic resonance imaging (bpMRI), excluding dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), is a potential replacement for multiparametric MRI (mpMRI) in diagnosing clinically significant prostate cancer (csPCa). An extensive international multireader multicase observer study was conducted to assess the noninferiority of bpMRI to mpMRI in csPCa diagnosis. METHODS: An observer study was conducted with 400 mpMRI examinations from four European centers, excluding examinations with prior prostate treatment or csPCa (Gleason grade [GG] ≥2) findings. Readers assessed bpMRI and mpMRI sequentially, assigning lesion-specific Prostate Imaging Reporting and Data System (PI-RADS) scores (3-5) and a patient-level suspicion score (0-100). The noninferiority of patient-level bpMRI versus mpMRI csPCa diagnosis was evaluated using the area under the receiver operating curve (AUROC) alongside the sensitivity and specificity at PI-RADS ≥3 with a 5% margin. The secondary outcomes included insignificant prostate cancer (GG1) diagnosis, diagnostic evaluations at alternative risk thresholds, decision curve analyses (DCAs), and subgroup analyses considering reader expertise. Histopathology and ≥3 yr of follow-up were used for the reference standard. KEY FINDINGS AND LIMITATIONS: Sixty-two readers (45 centers and 20 countries) participated. The prevalence of csPCa was 33% (133/400); bpMRI and mpMRI showed similar AUROC values of 0.853 (95% confidence interval [CI], 0.819-0.887) and 0.859 (95% CI, 0.826-0.893), respectively, with a noninferior difference of -0.6% (95% CI, -1.2% to 0.1%, p < 0.001). At PI-RADS ≥3, bpMRI and mpMRI had sensitivities of 88.6% (95% CI, 84.8-92.3%) and 89.4% (95% CI, 85.8-93.1%), respectively, with a noninferior difference of -0.9% (95% CI, -1.7% to 0.0%, p < 0.001), and specificities of 58.6% (95% CI, 52.3-63.1%) and 57.7% (95% CI, 52.3-63.1%), respectively, with a noninferior difference of 0.9% (95% CI, 0.0-1.8%, p < 0.001). At alternative risk thresholds, mpMRI increased sensitivity at the expense of reduced specificity. DCA demonstrated the highest net benefit for an mpMRI pathway in cancer-averse scenarios, whereas a bpMRI pathway showed greater benefit for biopsy-averse scenarios. A subgroup analysis indicated limited additional benefit of DCE MRI for nonexperts. Limitations included that biopsies were conducted based on mpMRI imaging, and reading was performed in a sequential order. CONCLUSIONS AND CLINICAL IMPLICATIONS: It has been found that bpMRI is noninferior to mpMRI in csPCa diagnosis at AUROC, along with the sensitivity and specificity at PI-RADS ≥3, showing its value in individuals without prior csPCa findings and prostate treatment. Additional randomized prospective studies are required to investigate the generalizability of outcomes.

• MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• multiparametrická magnetická rezonance * MeSH
• nádory prostaty * diagnostické zobrazování   patologie   MeSH
• odchylka pozorovatele MeSH
• senioři MeSH
• stupeň nádoru MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• srovnávací studie MeSH
• Geografické názvy
• Evropa MeSH