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 * epidemiology MeSH
- Communicable Diseases MeSH
- Laboratories * economics MeSH
- Humans MeSH
- Microbiology MeSH
- Pandemics MeSH
- SARS-CoV-2 MeSH
- Public Health MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND: Various explicit screening tools, developed mostly in central Europe and the USA, assist clinicians in optimizing medication use for older adults. The Turkish Inappropriate Medication use in oldEr adults (TIME) criteria set, primarily based on the STOPP/START criteria set, is a current explicit tool originally developed for Eastern Europe and subsequently validated for broader use in Central European settings. Reviewed every three months to align with the latest scientific literature, it is one of the most up-to-date tools available. The tool is accessible via a free mobile app and website platforms, ensuring convenience for clinicians and timely integration of updates as needed. Healthcare providers often prefer to use their native language in medical practice, highlighting the need for prescribing tools to be translated and adapted into multiple languages to promote optimal medication practices. OBJECTIVE: To describe the protocol for cross-cultural and language validation of the TIME criteria in various commonly used languages and to outline its protocol for clinical validation across different healthcare settings. METHODS: The TIME International Study Group comprised 24 geriatric pharmacotherapy experts from 12 countries. In selecting the framework for the study, we reviewed the steps and outcomes from previous research on cross-cultural adaptations and clinical validations of explicit tools. Assessment tools were selected based on both their validity in accurately addressing the relevant issues and their feasibility for practical implementation. The drafted methodology paper was circulated among the study group members for feedback and revisions leading to a final consensus. RESULTS: The research methodology consists of two phases. Cross-cultural adaptation/language validation phase follows the 8-step approach recommended by World Health Organization. This phase allows regions or countries to make modifications to existing criteria or introduce new adjustments based on local prescribing practices and available medications, as long as these adjustments are supported by current scientific evidence. The second phase involves the clinical validation, where participants will be randomized into two groups. The control group will receive standard care, while the intervention group will have their treatment evaluated by clinicians who will review the TIME criteria and consider its recommendations. A variety of patient outcomes (i.e., number of hospital admissions, quality of life, number of regular medications [including over the counter medications], geriatric syndromes and mortality) in different healthcare settings will be investigated. CONCLUSION: The outputs of this methodological report are expected to promote broader adoption of the TIME criteria. Studies building on this work are anticipated to enhance the identification and management of inappropriate medication use and contribute to improved patient outcomes.
The European Renal Association (ERA) Registry collects data on kidney replacement therapy (KRT) in patients with end-stage kidney disease (ESKD). This paper summarizes the ERA Registry Annual Report 2022, with a special focus on comparisons by sex. The supplement of this paper contains the complete ERA Registry Annual Report 2022. Data was collected from 53 national and regional KRT registries from 35 countries. Using this data, incidence, and prevalence of KRT, kidney transplantation rates, survival probabilities, and expected remaining lifetimes were calculated. In 2022, 530 million people of the European general population were covered by the ERA Registry. The incidence of KRT was 152 per million population (pmp). In incident patients, 54% were 65 years or older, 64% were male, and the most common primary renal disease (PRD) was diabetes mellitus (22%). At KRT initiation, 83% of patients received haemodialysis, 12% received peritoneal dialysis, and 5% underwent pre-emptive kidney transplantation. On 31 December 2022, the prevalence of KRT was 1074 pmp. In prevalent patients, 48% were 65 years or older, 62% were male, the most common PRD was of miscellaneous origin (18%), 56% of patients received haemodialysis, 5% received peritoneal dialysis, and 39% were living with a functioning graft. In 2022, the kidney transplantation rate was 40 pmp, with most kidneys coming from deceased donors (66%). For patients starting KRT between 2013 to 2017, 5-year survival probability was 52%. Compared with the general population, the expected remaining lifetime was 66% and 68% shorter for males and females, respectively, receiving dialysis, and 46% and 49% shorter for males and females, respectively, living with a functioning graft.
- Publication type
- Journal Article MeSH
- Review MeSH
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.SEQUOIA (ClinicalTrials.gov identifier: NCT03336333) is a phase III, randomized, open-label trial that compared the oral Bruton tyrosine kinase inhibitor zanubrutinib to bendamustine plus rituximab (BR) in treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The initial prespecified analysis (median follow-up, 26.2 months) and subsequent analysis (43.7 months) found superior progression-free survival (PFS; the primary end point) in patients who received zanubrutinib compared with BR. At a median follow-up of 61.2 months, median PFS was not reached in zanubrutinib-treated patients; median PFS was 44.1 months in BR-treated patients (hazard ratio [HR], 0.29; one-sided P = .0001). Prolonged PFS was seen with zanubrutinib versus BR in patients with mutated immunoglobulin heavy-chain variable region (IGHV) genes (HR, 0.40; one-sided P = .0003) and unmutated IGHV genes (HR, 0.21 [95% CI, 0.14 to 0.33]; one-sided P < .0001). Median overall survival (OS) was not reached in either treatment arm; estimated 60-month OS rates were 85.8% and 85.0% in zanubrutinib- and BR-treated patients, respectively. No new safety signals were detected. Adverse events were as expected with zanubrutinib; rate of atrial fibrillation was 7.1%. At a median follow-up of 61.2 months, the results supported the initial SEQUOIA findings and suggested that zanubrutinib was a favorable treatment option for untreated patients with CLL/SLL.
- MeSH
- Bendamustine Hydrochloride * administration & dosage therapeutic use MeSH
- Leukemia, Lymphocytic, Chronic, B-Cell * drug therapy mortality MeSH
- Progression-Free Survival MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Follow-Up Studies MeSH
- Piperidines therapeutic use administration & dosage adverse effects MeSH
- Antineoplastic Combined Chemotherapy Protocols * therapeutic use adverse effects MeSH
- Pyrazoles * therapeutic use administration & dosage adverse effects MeSH
- Pyrimidines * therapeutic use administration & dosage adverse effects MeSH
- Rituximab * administration & dosage therapeutic use adverse effects MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
The biosynthesis of the lincosamide antibiotics lincomycin A and celesticetin involves the pyridoxal-5'-phosphate (PLP)-dependent enzymes LmbF and CcbF, which are responsible for bifurcation of the biosynthetic pathways. Despite recognizing the same S-glycosyl-L-cysteine structure of the substrates, LmbF catalyses thiol formation through β-elimination, whereas CcbF produces S-acetaldehyde through decarboxylation-coupled oxidative deamination. The structural basis for the diversification mechanism remains largely unexplored. Here we conduct structure-function analyses of LmbF and CcbF. X-ray crystal structures, docking and molecular dynamics simulations reveal that active-site aromatic residues play important roles in controlling the substrate binding mode and the reaction outcome. Furthermore, the reaction selectivity and oxygen-utilization of LmbF and CcbF were rationally engineered through structure- and calculation-based mutagenesis. Thus, the catalytic function of CcbF was switched to that of LmbF, and, remarkably, both LmbF and CcbF variants gained the oxidative-amidation activity to produce an unnatural S-acetamide derivative of lincosamide.
PURPOSE: MRI-only adaptive brachytherapy (MRI-ABT) is the state-of-the-art for treating locally advanced cervical cancer (LACC) in combination with concurrent chemoradiotherapy. We aimed to evaluate the pattern of pelvic recurrence after the treatment. MATERIAL AND METHODS: A total of one hundred LACC patients were treated between January 2017 and December 2023 with concurrent chemoradiotherapy of 45 Gy in 25 fractions ± boost to lymphadenopathy (up to a maximum dose of 60 Gy in 25 fractions) with concurrent weekly cisplatin chemotherapy at the dose of 40 mg/m2/week, and MR-ABT. RESULTS: At a median follow-up of 30.2 months, there were 2 local recurrences (2%) and 9 regional pelvic recurrences (9%). The median time to local/regional recurrence was 11 months (range 6-21). For all stages, the 3-year local control was 97.66%, and the 3-year pelvic control was 89.45%. Twenty-four patients died during follow-up; the 3-year overall survival was 75.11%, and the 3-year disease-free survival was 70.97%. CONCLUSION: MRI-ABT combined with external beam radiotherapy and concurrent chemotherapy for LACC demonstrates excellent local and regional pelvic control. Most local/regional recurrences occur inside or at the edge of the external-beam irradiated field. Recurrences inside the field of brachytherapy are rare. Distant recurrences are the predominant cause of death in LACC patients treated with definitive CRT and MRI-ABT.
- MeSH
- Brachytherapy * methods MeSH
- Chemoradiotherapy * MeSH
- Cisplatin therapeutic use MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Recurrence, Local * radiotherapy MeSH
- Magnetic Resonance Imaging * MeSH
- Uterine Cervical Neoplasms * radiotherapy diagnostic imaging pathology MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Modafinil is primarily used to treat narcolepsy but is also used as an off-label cognitive enhancer. Functional magnetic resonance imaging studies indicate that modafinil modulates the connectivity of neocortical networks primarily involved in attention and executive functions. However, much less is known about the drug's effects on subcortical structures. Following preliminary findings, we evaluated modafinil's activity on the connectivity of distinct cerebellar regions with the neocortex. We assessed the spatial relationship of these effects with the expression of neurotransmitter receptors/transporters. METHODS: Patterns of resting-state functional magnetic resonance imaging connectivity were estimated in 50 participants from scans acquired pre- and postadministration of a single (100 mg) dose of modafinil (n = 25) or placebo (n = 25). Using specific cerebellar regions as seeds for voxelwise analyses, we examined modafinil's modulation of cerebellar-neocortical connectivity. Next, we conducted a quantitative evaluation of the spatial overlap between the modulation of cerebellar-neocortical connectivity and the expression of neurotransmitter receptors/transporters obtained by publicly available databases. RESULTS: Modafinil increased the connectivity of crus I and vermis IX with prefrontal regions. Crus I connectivity changes were associated with the expression of dopaminergic D2 receptors. The vermis I-II showed enhanced coupling with the dorsal anterior cingulate cortex and matched the expression of histaminergic H3 receptors. The vermis VII-VIII displayed increased connectivity with the visual cortex, an activity associated with dopaminergic and histaminergic neurotransmission. CONCLUSIONS: Our study reveals modafinil's modulatory effects on cerebellar-neocortical connectivity. The modulation mainly involves crus I and the vermis and spatially overlaps the distribution of dopaminergic and histaminergic receptors.
- MeSH
- Adult MeSH
- Humans MeSH
- Magnetic Resonance Imaging * MeSH
- Young Adult MeSH
- Modafinil * pharmacology administration & dosage MeSH
- Cerebellum * drug effects diagnostic imaging metabolism MeSH
- Neocortex drug effects metabolism diagnostic imaging MeSH
- Neural Pathways drug effects metabolism MeSH
- Wakefulness-Promoting Agents pharmacology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
The 2024 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for chronic kidney disease (CKD) evaluation and management bring important updates, particularly for European laboratories. These guidelines emphasize the need for harmonization in CKD testing, promoting the use of regional equations. In Europe, the European Kidney Function Consortium (EKFC) equation is particularly suited for European populations, particularly compared to the CKD-EPI 2021 race-free equation. A significant focus is placed on the combined use of creatinine and cystatin C to estimate glomerular filtration rate (eGFRcr-cys), improving diagnostic accuracy. In situations where eGFR may be inaccurate or clinically insufficient, the guidelines encourage the use of measured GFR (mGFR) through exogenous markers like iohexol. These guidelines emphasize the need to standardize creatinine and cystatin C measurements, ensure traceability to international reference materials, and adopt harmonized reporting practices. The recommendations also highlight the importance of incorporating risk prediction models, such as the Kidney Failure Risk Equation (KFRE), into routine clinical practice to better tailor patient care. This article provides a European perspective on how these KDIGO updates should be implemented in clinical laboratories to enhance CKD diagnosis and management, ensuring consistency across the continent.
- MeSH
- Renal Insufficiency, Chronic * diagnosis therapy MeSH
- Cystatin C blood MeSH
- Glomerular Filtration Rate * MeSH
- Laboratories, Clinical MeSH
- Creatinine blood MeSH
- Humans MeSH
- Practice Guidelines as Topic * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Geographicals
- Europe MeSH
BACKGROUND: Trichophyton mentagrophytes ITS genotype VII (TMVII) has recently been identified in France as the causative agent of dermatophyte infections transmitted during sexual activity among men who have sex with men (MSM). OBJECTIVES: Our objective was to provide new insights into the epidemiology, clinical presentation and treatment of TMVII infections based on cases diagnosed from October 2022 to September 2023 in three medical mycology laboratories in Paris. Additionally, we aimed to perform molecular characterization of TMVII strains collected in Paris, as well as in Switzerland. METHODS: We identified all isolates from skin and hair belonging to the T. mentagrophytes complex by sequencing the ITS region. For isolates corresponding to TMVII, clinical data were retrieved from medical records. For all available TMVII strains that we isolated since January 2021, we sequenced tef1α and tubb and determined the MAT locus idiomorph. RESULTS: We identified 32 cases of TMVII Infections. All cases occurred in men, 30 of whom reported having sex with men. Fifteen cases were sporadic cases including four among sex workers. The other 17 cases belonged to a single cluster involving a tantric masseur who infected 15 clients and his roommate. The median time from massage to lesion onset was 16 [2-52] days. Except for one patient, all other patients received systemic antifungal treatment with terbinafine. We observed five patients whose cultures remained positive even after 3-4 weeks of treatment and five patients experienced a relapse of the infection after discontinuing antifungal treatment. All French isolates exhibited identical tef1α and tubb sequences, as well as the same MAT idiomorph locus. They displayed variations in the tef1α sequence compared to isolates from Switzerland and the Czech Republic. CONCLUSIONS: We confirm the active circulation of TMVII among MSM in France, which is associated with challenges in diagnosis, treatment and prevention.
- MeSH
- Antifungal Agents * therapeutic use MeSH
- Arthrodermataceae MeSH
- Adult MeSH
- Genotype * MeSH
- Homosexuality, Male MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Terbinafine therapeutic use MeSH
- Tinea * microbiology epidemiology drug therapy MeSH
- Trichophyton * genetics isolation & purification MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- France MeSH
AIMS: Sinonasal adenosquamous carcinoma (ASC) is a rare tumour classified as a variant of squamous cell carcinoma, exhibiting both squamous and glandular differentiation. ASC has a poorer prognosis compared to sinonasal mucoepidermoid carcinoma (MEC), another uncommon tumour in this region. ASC is believed to originate from metaplastic squamous epithelium, though it may also arise from respiratory epithelium in respiratory epithelial adenomatoid hamartoma (REAH) or seromucinous glands in seromucinous hamartoma (SH). METHODS AND RESULTS: Five cases of sinonasal ASC were retrieved from our registry. Initially, they were classified as sinonasal MEC (n = 3), ASC (n = 2), and carcinoma ex REAH (n = 1). All cases showed adenosquamous malignant proliferation beneath the surface respiratory epithelium with occasional squamous metaplasia, except for one case that showed dysplasia. The respiratory epithelium exhibited an inverted growth pattern consistent with REAH/SH, and displayed atypical sinonasal glands (ASGSH) arising within seromucinous hamartoma. Next-generation sequencing (NGS) revealed multiple pathogenic mutations in two cases, and in case 4 GGA2::PRKCB and EYA2::SERINC3 gene fusions. One case was positive for high-risk HPV. None of the cases exhibited CRTC1/3::MAML2 gene fusion. CONCLUSION: The connection between ASGSH and ASC has not been described in the literature. There is a growing need for additional studies on the morphological, immunohistochemical, and genetic aspects of these tumours. SH/REAH may serve as precursor lesions in the progression of atypical sinonasal glands to malignancy, and their role in tumour development deserves further investigation.
- MeSH
- Carcinoma, Adenosquamous * pathology genetics MeSH
- Adult MeSH
- Hamartoma * pathology genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- Paranasal Sinus Neoplasms pathology genetics MeSH
- Respiratory Mucosa pathology MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH