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

The Global Alliance for Genomics and Health (GA4GH) Phenopacket Schema was released in 2022 and approved by ISO as a standard for sharing clinical and genomic information about an individual, including phenotypic descriptions, numerical measurements, genetic information, diagnoses, and treatments. A phenopacket can be used as an input file for software that supports phenotype-driven genomic diagnostics and for algorithms that facilitate patient classification and stratification for identifying new diseases and treatments. There has been a great need for a collection of phenopackets to test software pipelines and algorithms. Here, we present Phenopacket Store. Phenopacket Store v.0.1.19 includes 6,668 phenopackets representing 475 Mendelian and chromosomal diseases associated with 423 genes and 3,834 unique pathogenic alleles curated from 959 different publications. This represents the first large-scale collection of case-level, standardized phenotypic information derived from case reports in the literature with detailed descriptions of the clinical data and will be useful for many purposes, including the development and testing of software for prioritizing genes and diseases in diagnostic genomics, machine learning analysis of clinical phenotype data, patient stratification, and genotype-phenotype correlations. This corpus also provides best-practice examples for curating literature-derived data using the GA4GH Phenopacket Schema.

• MeSH
• Algorithms MeSH
• Databases, Genetic MeSH
• Phenotype * MeSH
• Genomics * methods   MeSH
• Humans MeSH
• Software * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

In 2019, Pantoea piersonii was initially isolated from the interior surfaces of the International Space Station. This microorganism is a species within the genus Pantoea in the family Erwiniaceae, belonging to the order Enterobacterales. Recent literature has documented four cases of its isolation. Despite initial predictions suggesting the non-pathogenicity of P. piersonii strains, evidence from observed cases indicates potential pathogenicity. According to documented evidence in the literature, this microorganism is capable of causing severe and life-threatening conditions, including sepsis. Traditional tests, as well as automated systems, may fail to provide complete differentiation due to these similarities. While MALDI-TOF MS is a valuable tool for identification in clinical diagnostic microbiology, sequencing may be necessary for precise identification. To determine the antibiotic susceptibility profile, various methods can be utilized, including minimum inhibitory concentration determination, disk diffusion testing (Kirby-Bauer test), genotypic resistance assays (PCR and sequencing), and automated systems. The literature reports a limited number of cases associating P. piersonii with human infection. This study contributes to this body of knowledge by reporting a novel case in which P. piersonii was isolated from a tissue sample for the first time. In this case report, the patient achieved recovery following the administration of appropriate antibiotic treatment based on the diagnosis. It underscores the need for precise identification and understanding of its pathogenicity.

• MeSH
• Anti-Bacterial Agents * pharmacology   therapeutic use   MeSH
• Enterobacteriaceae Infections * microbiology   diagnosis   drug therapy   MeSH
• Humans MeSH
• Microbial Sensitivity Tests * MeSH
• Pantoea * isolation & purification   genetics   pathogenicity   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

The forskolin-induced swelling assay (FIS) in patient-derived intestinal organoids (PDIOs), used to determine in vitro responsiveness to elexacaftor/tezacaftor/ivacaftor (ETI), showed variability in swelling among PDIOs obtained from people with CF (pwCF) carrying the same F508del/F508del CFTR genotype. We aimed to characterise the effect of ETI on the transcriptional activity of PDIOs-derived cells to understand the intracellular processes triggered by ETI and the differences in treatment response. Six high- and six low-responding PDIOs to ETI, derived from F508del/F508del pwCF, were incubated with or without ETI for 2 to 6 h. Gene expression was assessed using 3'-mRNA sequencing and modelled using negative binomial models. Incubation with ETI resulted in a significant upregulation of several biological processes: mostly related to chemokines and signalling, chemotaxis, and tissue development processes. No changes were observed in abundance of the CFTR transcripts or in CFTR-related gene sets and pathways. The genes and pathways associated with ETI did not overlap with those whose expression changed with time only. PDIOs with a high FIS response did not significantly differ in any interpretable gene from the FIS-low organoids. The changes in the PDIOs gene expression upon the exposure to ETI cannot explain differences in the magnitude of PDIOs FIS-measured response to ETI. In conclusion, on incubation with ETI, genes of the CFTR-related pathways do not change their transcriptional activity; instead, overexpression was observed in genes of inflammatory-like cytokine response and receptor activation pathways.

• MeSH
• Chloride Channel Agonists therapeutic use   pharmacology   MeSH
• Aminophenols * therapeutic use   pharmacology   MeSH
• Benzodioxoles * therapeutic use   pharmacology   MeSH
• Quinolones * pharmacology   therapeutic use   MeSH
• Cystic Fibrosis * genetics   drug therapy   MeSH
• Drug Combinations MeSH
• Indoles * pharmacology   MeSH
• Humans MeSH
• Organoids * metabolism   MeSH
• Cystic Fibrosis Transmembrane Conductance Regulator genetics   MeSH
• Pyrazoles * pharmacology   MeSH
• Pyridines pharmacology   MeSH
• Pyrrolidines pharmacology   MeSH
• Pyrroles pharmacology   MeSH
• Gene Expression Profiling methods   MeSH
• Intestines drug effects   MeSH
• Transcriptome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Palindromický revmatismus (PR) je klinický syndrom charakterizovaný opětovnými epizodami vzplanutí bolesti, otoku a zarudnutí kloubu/ů a přilehlých tkání s kompletní remisí bez zbytkového poškození. Ultrasonografickým zobrazováním se zjistilo, že u těchto epizod jde hlavně o extrakapsulární zánět. Epizodická vzplanutí jsou u PR zpravidla monoartikulární a postihují nejčastěji tytéž klouby jako revmatoidní artritida (RA), tj. hlavně proximální interfalangeální, metakarpofalangeální a zápěstní klouby. Klinická zkušenost nabízí hodnotit PR jako neobvyklou vstupní formu RA. Genotypové studie, recentně zvláště sekvenování kompletního exomu, však ukázaly rozdíly mezi PR a RA; u části PR byla zjištěna také mutace MEFV genu. Nejčastější prognózou PR je vyústění do RA; platí to hlavně pro PR s protilátkami proti citrulinovaným peptidům. Konečnou diagnózou u PR ale může být i jiné systémové autoimunitní revmatické onemocnění, např. systémový lupus erythematodes. Rekurentní zánětlivá vzplanutí mohou přetrvávat beze změny i po léta, nebo naopak dojde k dlouhodobé remisi, ale opětovné vzplanutí se nedá vyloučit. Terapie PR napodobuje léčbu RA; úspěšnou blokaci rekurencí extrakapsulárního zánětu u PR je možné hodnotit obdobně jako léčebné „okno příležitosti“ u RA.

Palindromic rheumatism (PR) is a clinical syndrome characterized by recurrent, transient episodes of joint pain, erythema, and swelling, typically without resulting in permanent joint damage. Ultrasonographic studies have shown that extra-capsular inflammation is a distinctive feature of this condition. PR flares are frequently monoarticular and commonly involve joints also affected in rheumatoid arthritis (RA), particularly the proximal interphalangeal, metacarpophalangeal, and wrist joints. Although clinical experience has long suggested that PR may represent an atypical form or precursor of RA, recent genetic analyses, particularly whole-exome sequencing, have revealed notable distinctions between the two diseases. In some patients with PR, mutations in the MEFV gene have been identified, further supporting its heterogeneous nature. RA remains the most frequent definitive diagnosis in patients with PR, especially in those positive for anti-citrullinated peptide antibodies. However, a subset of PR cases may evolve into other systemic autoimmune rheumatic diseases, such as systemic lupus erythematosus. In many patients, PR persists for years with recurrent flares or may enter remission, which may be prolonged but not necessarily permanent. Lifelong monitoring is essential, as flares can recur unpredictably. Management strategies for PR often mirror those of RA. Early and effective suppression of extra-capsular inflammation during PR flares may be as crucial as the "window of opportunity" concept in RA, potentially influencing long-term outcomes

• Keywords
• palindromický revmatismus,
• MeSH
• Genotype MeSH
• Humans MeSH
• Prognosis MeSH
• Disease Progression MeSH
• Prospective Studies MeSH
• Rheumatic Diseases * diagnosis   drug therapy   pathology   MeSH
• Arthritis, Rheumatoid MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

BACKGROUND: Since the incidence of vancomycin-resistant enterococci (VRE) is increasing and treatment options remain limited, we aimed to investigate the epidemiology of vancomycin- and tigecycline-resistant enterococci in a university hospital using whole genome sequencing (WGS). METHODS: Between April and December 2021, 102 VRE isolates were collected from a single tertiary care hospital in the Czech Republic. Forty selected isolates underwent antimicrobial susceptibility testing and WGS (Illumina short reads and long reads with MinION in selected isolates). RESULTS: All Enterococcus faecium isolates were resistant to ampicillin, carrying the PBP5_Met485Ala, PBP5_Glu629Val, and fluoroquinolones carrying the GyrA_Ser83Ile and ParC_Ser80Ile substitutions. The vanA operon was found on pELF2-like plasmids and plasmids carrying rep17 and/or rep18b genes. The novel Tn1546 structural variants were identified in vanA-carrying isolates. The vanB operon was located on the chromosome within a Tn1549 structural variant. Linezolid resistance was detected in one isolate carrying the 23S rDNA_G2576T substitution. Twenty-two isolates were resistant to tigecycline (tet(L), tet(M) and rpsJ_del 155-166 or RpsJ_Lys57Arg). Discrepancies between phenotypic and genotypic resistance profiles were observed for daptomycin (RpoB_Ser491Phe), trimethoprim/sulfamethoxazole (dfrG gene), nitrofurantoin (NmrA_Gln48Lys substitution without the EF0404 and EF0648 genes) and tetracycline (truncated TetM). The two multilocus sequence typing (MLST) schemes identified different numbers of STs: 5 STs, with ST117 as the predominant one (n = 32, 80%), versus 10 STs, with ST138 (27.5%), ST136 (25%), and ST1067 (20%) being the most frequent, respectively. The whole genome MLST revealed clonal clustering (0-7 allele differences) among isolates of the same ST. When comparing ST117 isolates from our study with 2,204 ST117 isolates from 15 countries, only one Czech isolate clustered closely with strains from Germany and the Netherlands, differing by just 16 alleles. CONCLUSIONS: The spread of E. faecium isolates ST117 resistant to vancomycin and tigecycline was identified. The discrepancies between resistance genotypes and phenotypes highlight the importance of combining molecular and phenotypic surveillance in antimicrobial resistance monitoring.

• MeSH
• Anti-Bacterial Agents * pharmacology   MeSH
• Bacterial Proteins genetics   MeSH
• Enterococcus faecium * genetics   drug effects   isolation & purification   classification   MeSH
• Vancomycin-Resistant Enterococci * genetics   drug effects   isolation & purification   MeSH
• Genome, Bacterial MeSH
• Gram-Positive Bacterial Infections * microbiology   epidemiology   MeSH
• Humans MeSH
• Microbial Sensitivity Tests MeSH
• Drug Resistance, Multiple, Bacterial genetics   MeSH
• Multilocus Sequence Typing MeSH
• Vancomycin Resistance genetics   MeSH
• Whole Genome Sequencing MeSH
• Tigecycline * pharmacology   MeSH
• Vancomycin * pharmacology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

INTRODUCTION: Prader-Willi syndrome (PWS) is primarily caused by a paternal microdeletion of the 15q11-q13 region, maternal uniparental disomy (mUPD) or unbalanced translocations. The MKRN3 gene, located within 15q11-q13, is a master regulator of pubertal initiation. We aimed to compare variant pubertal onset and progression with recent normative data and to correlate it with abnormal MKRN3 gene status. METHODS: Age at pubarche, gonadarche, subsequent pubertal progression and bone age (BA) at gonadarche were investigated in 37 PWS patients (18 females) who already entered pubarche and/or gonadarche with median age 11.1 (95% CI: 6.4 - 18.8) years. All patients were re-tested to confirm genetic subtypes of PWS. The MKRN3 gene was analyzed using single gene sequencing. RESULTS: Out of 37 subjects, 22 had microdeletion and 15 mUPD. Regardless of genetic subtypes and MKRN3 gene status, no correlation between genotypes and the pubertal pattern was found. They initiated pubarche early - girls at 7.4 (95%CI:6.4-8.4), and boys at 9.2 (8.2-10.2) years. The subsequent progression from PH2 to PH4 (pubic hair development) was prolonged to 3.7 years in girls (1.5-5.9;p<0.05), and 2.9 in boys (2.2-3.6;p<0.001). The age at gonadarche was adequate - 10.0 years in girls (8.8-11.2), and 11.0 in boys (9.8-12.1). Progression rate of breast development from B2 to B4 was 3.9 (0.2-7.5) years in girls and of testicular volume from 4 ml to 15ml was 3.8 (0.0-8.1) years in boys. The BA at gonadarche is advanced by 0.6 ± 1.1 years (p<0.001). CONCLUSIONS: Children with PWS, regardless of the genetic subtype and/or MKRN3 status, had an early pubarche and normally timed gonadarche. Pubarche progression was slower. Advanced BA was significantly correlated with gonadarche.

• MeSH
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Prader-Willi Syndrome * genetics   physiopathology   MeSH
• Disease Progression MeSH
• Puberty * physiology   genetics   MeSH
• Ribonucleoproteins genetics   MeSH
• Ubiquitin-Protein Ligases genetics   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

OBJECTIVES: While the reported incidence of non-tuberculous mycobacterial (NTM) infections is increasing, the true prevalence remains uncertain due to limitations in diagnostics and surveillance. The emergence of rare and novel species underscores the need for characterization to improve surveillance, detection, and management. METHODS: We performed whole-genome sequencing (WGS) and/or targeted deep-sequencing using the Deeplex Myc-TB assay on all NTM isolates collected in Slovakia and the Czech Republic between the years 2019 to 2023 that were unidentifiable at the species level by the routine diagnostic line probe assays (LPA) GenoType CM/AS and NTM-DR. Minimal inhibitory concentrations against amikacin, ciprofloxacin, moxifloxacin, clarithromycin, and linezolid were determined, and clinical data were collected. RESULTS: Twenty-eight cultures from different patients were included, of which 9 (32.1%) met the clinically relevant NTM disease criteria. The majority of those had pulmonary involvement, while two children presented with lymphadenitis. Antimycobacterial resistance rates were low. In total, 15 different NTM species were identified, predominantly rare NTM like M. neoaurum, M. kumamotonense and M. arupense. Notably, clinically relevant M. chimaera variants were also identified with WGS and Deeplex-Myc TB, which, unlike other M. chimaera strains, appeared to be undetectable by LPA assays. Deeplex detected four mixed infections that were missed by WGS analysis. In contrast, WGS identified two novel species, M. celatum and M. branderi, which were not detected by Deeplex-Myc TB. Importantly, one of these novel species strains was associated with clinically relevant pulmonary disease. DISCUSSION: Our study demonstrates the clinical relevance of uncommon NTM and the effectiveness of targeted deep-sequencing combined with WGS in identifying rare and novel NTM species.

• MeSH
• Anti-Bacterial Agents * pharmacology   MeSH
• Mycobacterium Infections, Nontuberculous * microbiology   diagnosis   MeSH
• Drug Resistance, Bacterial MeSH
• Child MeSH
• Adult MeSH
• Genotype MeSH
• Clinical Relevance MeSH
• Middle Aged MeSH
• Humans MeSH
• Microbial Sensitivity Tests * MeSH
• Adolescent MeSH
• Nontuberculous Mycobacteria * drug effects   genetics   isolation & purification   MeSH
• Child, Preschool MeSH
• Whole Genome Sequencing * MeSH
• Aged MeSH
• High-Throughput Nucleotide Sequencing MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Slovakia MeSH

High-grade B-cell lymphomas (HGBCLs) are aggressive blood cancers with a severe disease course, especially when the central nervous system (CNS) is involved. Standard histological examination depends on tissue availability and is currently supplemented with molecular tests, as the status of MYC, BCL2, or BCL6 gene rearrangements is required for proper lymphoma classification. This case report demonstrates the relevance of cerebrospinal fluid (CSF) cell-free DNA testing by integrative next-generation sequencing (NGS) panel. The benefit of this approach resided in tumor genotyping alongside the proof of CNS progression despite MRI negativity, revealing a clonal relationship with the primary tumor lesion. In addition, our strategy allowed us to classify the tumor as DLBCL/HGBL-MYC/BCL2 entity. In clinical practice, such a minimally invasive approach provides a more sensitive tool than standard imaging and cell analyzing techniques, enabling more accurate disease monitoring and relapse prediction in particular cases.

• MeSH
• Lymphoma, B-Cell genetics   pathology   diagnosis   diagnostic imaging   MeSH
• Circulating Tumor DNA genetics   MeSH
• Lymphoma, Large B-Cell, Diffuse genetics   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local pathology   genetics   MeSH
• Magnetic Resonance Imaging * MeSH
• Biomarkers, Tumor genetics   MeSH
• Central Nervous System Neoplasms genetics   pathology   diagnostic imaging   MeSH
• High-Throughput Nucleotide Sequencing * MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

Adenoid cystic carcinomas (AdCC) of salivary gland origin have long been categorized as fusion-defined carcinomas owing to the almost universal presence of the gene fusion MYB::NFIB , or less commonly MYBL1::NFIB. Sinonasal AdCC is an aggressive salivary gland malignancy with no effective systemic therapy. Therefore, it is urgent to search for potentially targetable genetic alterations associated with AdCC. We have searched the authors' registries and selected all AdCCs arising in the sinonasal tract. The tumors were examined histologically, immunohistochemically, by next generation sequencing (NGS) and/or fluorescence in situ hybridization (FISH) looking for MYB/MYBL1 and/or NFIB gene fusions or any novel gene fusions and/or mutations. In addition, all tumors were tested for HPV by genotyping using (q)PCR. Our cohort comprised 88 cases of sinonasal AdCC, predominantly characterized by canonical MYB::NFIB (49 cases) and MYBL1::NFIB (9 cases) fusions. In addition, noncanonical fusions EWSR1::MYB ; ACTB::MYB; ESRRG::DNM3 , and ACTN4::MYB were identified by NGS, each of them in 1 case. Among nine fusion-negative AdCCs, FISH detected rearrangements in MYB (7 cases) , NFIB (1 case), and EWSR1 (1 case). Six AdCCs lacked fusions or gene rearrangements, while 11 cases were unanalyzable. Mutational analysis was performed by NGS in 31/88 (35%) AdCCs. Mutations in genes with established roles in oncogenesis were identified in 21/31 tumors (68%), including BCOR (4/21; 19%), NOTCH1 (3/21; 14%), EP300 (3/21; 14%), SMARCA4 (2/21; 9%), RUNX1 (2/21; 9%), KDM6A (2/21; 9%), SPEN (2/21; 9%), and RIT1, MGA, RB1, PHF6, PTEN, CREBBP, DDX41, CHD2, ROS1, TAF1, CCD1, NF1, PALB2, AVCR1B, ARID1A, PPM1D, LZTR1, GEN1 , PDGFRA , each in 1 case (1/21; 5%). Additional 24 cases exhibited a spectrum of gene mutations of uncertain pathogenetic significance. No morphologic differences were observed between AdCCs with MYBL1::NFIB and MYB::NFIB fusions. Interestingly, mutations in the NOTCH genes were seen in connection with both canonical and noncanonical fusions, and often associated with high-grade histology or metatypical phenotype, as well as with poorer clinical outcome. Noncanonical fusions were predominantly observed in metatypical AdCCs. These findings emphasize the value of comprehensive molecular profiling in correlating morphologic characteristics, genetic landscape, and clinical behavior in AdCC.

• MeSH
• Carcinoma, Adenoid Cystic * genetics   pathology   MeSH
• Adult MeSH
• Phenotype MeSH
• Gene Fusion MeSH
• Oncogene Proteins, Fusion genetics   MeSH
• Genetic Predisposition to Disease MeSH
• In Situ Hybridization, Fluorescence * MeSH
• Immunohistochemistry MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Mutation * MeSH
• DNA Mutational Analysis MeSH
• Biomarkers, Tumor * genetics   MeSH
• Paranasal Sinus Neoplasms * genetics   pathology   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• NFI Transcription Factors genetics   MeSH
• High-Throughput Nucleotide Sequencing * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH