OBJECTIVE: To determine the oncological impact of extended pelvic lymph node dissection (ePLND) vs standard PLND (sPLND) during radical cystectomy (RC) in clinically lymph node-positive (cN+) bladder cancer (BCa). PATIENTS AND METHODS: In this retrospective, multicentre study we included 969 patients who underwent RC with sPLND (internal/external iliac and obturator lymph nodes) or ePLND (sPLND plus common iliac and presacral nodes) with or without platin-based peri-operative chemotherapy for cTany N1-3 M0 BCa between 1991 and 2022. We assessed the impact of ePLND on recurrence-free survival (RFS) and the distribution of recurrences (locoregional and distant recurrences). The secondary endpoint was overall survival (OS). We performed propensity-score matching using covariates associated with the extent of PLND in univariable logistic regression analysis. The association of the extent of PLND with RFS and OS was investigated using Cox regression models. RESULTS: Of 969 cN+ patients, 510 were 1:1 matched on propensity scores. The median (interquartile range [IQR]) time to recurrence was 8 (4-16) months, and median (IQR) follow-up of alive patients was 30 (13-51) months. Disease recurrence was observed in 104 patients in the ePLND and 107 in the sPLND group. Of these, 136 (27%), 47 (9.2%) and 19 patients (3.7%) experienced distant, locoregional, or both distant and locoregional disease recurrence, respectively. When stratified by the extent of PLND, we did not find a difference in recurrence patterns (P > 0.05). ePLND improved neither RFS (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.70-1.19; P = 0.5) nor OS (HR 0.78, 95% CI 0.60-1.01; P = 0.06) compared to sPLND. Stratification by induction chemotherapy did not change outcomes. CONCLUSION: Performing an ePLND at the time of RC in cN+ patients improved neither RFS nor OS compared to sPLND, regardless of induction chemotherapy status. Pretreatment risk stratification is paramount to identify ideal candidates for RC with ePLND as part of a multimodal treatment approach.

• MeSH
• cystektomie MeSH
• lidé MeSH
• lokální recidiva nádoru * patologie   MeSH
• lymfadenektomie MeSH
• lymfatické uzliny chirurgie   patologie   MeSH
• nádory močového měchýře * farmakoterapie   chirurgie   MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND: Schistosoma mansoni was introduced from Africa to the Americas during the transatlantic slave trade and remains a major public health problem in parts of South America and the Caribbean. This study presents a comprehensive comparative analysis of three S. mansoni strains with different geographical origins-from Liberia, Belo Horizonte and Puerto Rico. We demonstrated significant variation in virulence and host-parasite interactions. METHODS: We investigated the phenotypic characteristics of the parasite and its eggs, as well as the immunopathologic effects on laboratory mouse organ systems. RESULTS: Our results show significant differences in worm morphology, worm burden, egg size, and pathologic organ changes between these strains. The Puerto Rican strain showed the highest virulence, as evidenced by marked liver and spleen changes and advanced liver fibrosis indicated by increased collagen content. In contrast, the strains from Liberia and Belo Horizonte had a less pathogenic profile with less liver fibrosis. We found further variations in granuloma formation, cytokine expression and T-cell dynamics, indicating different immune responses. CONCLUSION: Our study emphasizes the importance of considering intra-specific variations of S. mansoni for the development of targeted therapies and public health strategies. The different virulence patterns, host immune responses and organ pathologies observed in these strains provide important insights for future research and could inform region-specific interventions for schistosomiasis control.

• MeSH
• cytokiny metabolismus   MeSH
• interakce hostitele a parazita MeSH
• játra * parazitologie   patologie   MeSH
• myši MeSH
• Schistosoma mansoni * patogenita   genetika   imunologie   MeSH
• schistosomiasis mansoni * parazitologie   imunologie   patologie   MeSH
• slezina parazitologie   patologie   imunologie   MeSH
• virulence MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Libérie MeSH
• Portoriko MeSH

Sinonasal carcinomas represent a rare and diverse group of tumors, presenting diagnostic complexities due to their varied histological and molecular features. To ensure accurate differentiation among these malignancies, a systematic and stepwise approach is paramount. Even with the morphological similarities between poorly differentiated (non) keratinizing sinonasal squamous cell carcinoma (SNSCC) and DEK::AFF2 SNSCC, the two lesions are distinguishable using the surrogate immunohistochemical marker AFF2 or molecular testing for DEK::AFF2 mutation. We report a rare case of SMARCB1-retained DEK::AFF2 papillary non-keratinizing SNSCC in a 53-year-old female, who presented with a polypoid mass corresponding to the left middle turbinate. Following the surgical resection of the tumor and locoregional lymph nodes, adjuvant radiotherapy was administered to eradicate any residual cancer cells that may have remained after surgery.

• MeSH
• algoritmy MeSH
• buněčná diferenciace MeSH
• jaderné proteiny MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické uzliny MeSH
• nádory vedlejších dutin nosních * diagnóza   genetika   MeSH
• spinocelulární karcinom * diagnóza   genetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Kazuistika popisuje případ pacienta s metastatickým karcinomem distálního jícnu a kardie, který v rámci metastatického onemocnění byl léčen několika řadami systémové léčby s opakovaným navozením léčebné odpovědi a kontroly onemocnění. V rámci čtvrté linie léčby trifluridin/tipiracilem byla pozorována léčebná odpověď výrazně převyšující odpověď na léčbu v registrační studii TAGS. Efektivní léčba trifluridin/tipiracilem současně nevedla ke zhoršení celkového stavu pacienta a měla minimální vliv na kvalitu života.

This case report describes a patient with metastatic distal esophageal and cardia cancer who was treated with several lines of systemic therapy with repeated response and disease control. In the fourth-line, trifluridine/tipiracil treatment, a treatment response significantly superior to that observed in the TAGS registration study was observed. At the same time, effective trifluridine/tipiracil treatment did not lead to deterioration in the patient's general condition and had minimal impact on quality of life.

• Klíčová slova
• trifluridin/tipiracil,
• MeSH
• antitumorózní látky * aplikace a dávkování   škodlivé účinky   MeSH
• fixní kombinace léků MeSH
• gastrointestinální nádory * farmakoterapie   terapie   MeSH
• kombinovaná farmakoterapie metody   MeSH
• lidé MeSH
• lymfatické uzliny diagnostické zobrazování   patologie   MeSH
• metastázy nádorů MeSH
• progrese nemoci MeSH
• pyrrolidiny aplikace a dávkování   škodlivé účinky   MeSH
• retroperitoneální prostor diagnostické zobrazování   patologie   MeSH
• senioři MeSH
• terapie neúspěšná MeSH
• trifluridin aplikace a dávkování   škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• kazuistiky MeSH

Despite the adenoids are regularly removed in patients with mucopolysaccharidoses (MPS), the underlying tissue and cellular pathologies remain understudied. We characterized an (immuno)histopathologic and ultrastructural phenotype dominated by lysosomal storage changes in a specific subset of adenotonsillar paracortical cells in 8 MPS patients (3 MPS I, 3 MPS II, and 2 MPS IIIA). These abnormal cells were effectively detected by an antibody targeting the lysosomal membrane tetraspanin CD63. Important, CD63+ storage vacuoles in these cells lacked the monocytes/macrophages lysosomal marker CD68. Such a distinct patterning of CD63 and CD68 was not present in a patient with infantile neurovisceral variant of acid sphingomyelinase deficiency. The CD63+ storage pathology was absent in two MPS I patients who either received enzyme-replacement therapy or underwent hematopoietic stem cells transplantation prior the adenoidectomy. Our study demonstrates novel features of lysosomal storage patterning and suggests diagnostic utility of CD63 detection in adenotonsillar lymphoid tissue of MPS patients.

• MeSH
• antigeny CD63 MeSH
• enzymová substituční terapie MeSH
• lidé MeSH
• lymfoidní tkáň patologie   MeSH
• lyzozomy MeSH
• mukopolysacharidózy * diagnóza   farmakoterapie   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Congenital athymia is a life-limiting disorder due to rare inborn errors of immunity causing impaired thymus organogenesis or abnormal thymic stromal cell development and function. Athymic infants have a T-lymphocyte-negative, B-lymphocyte-positive, natural killer cell-positive immunophenotype with profound T-lymphocyte deficiency and are susceptible to severe infections and autoimmunity. Patients variably display syndromic features. Expanding access to newborn screening for severe combined immunodeficiency and T lymphocytopenia and broad genetic testing, including next-generation sequencing technologies, increasingly facilitate their timely identification. The recommended first-line treatment is allogeneic thymus transplantation, which is a specialized procedure available in Europe and the United States. Outcomes for athymic patients are best with early diagnosis and thymus transplantation before the development of infectious and inflammatory complications. These guidelines on behalf of the European Society for Immunodeficiencies provide a comprehensive review for clinicians who manage patients with inborn thymic stromal cell defects; they offer clinical practice recommendations focused on the diagnosis, investigation, risk stratification, and management of congenital athymia with the aim of improving patient outcomes.

• MeSH
• lidé MeSH
• management nemoci MeSH
• novorozenec MeSH
• syndromy imunologické nedostatečnosti * terapie   diagnóza   imunologie   MeSH
• thymus imunologie   MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• směrnice pro lékařskou praxi MeSH
• Geografické názvy
• Evropa MeSH

The establishment of long-lasting immunity against pathogens is facilitated by the germinal center (GC) reaction, during which B cells increase their antibody affinity and differentiate into antibody-secreting cells (ASC) and memory cells. These events involve modifications in chromatin packaging that orchestrate the profound restructuring of gene expression networks that determine cell fate. While several chromatin remodelers were implicated in lymphocyte functions, less is known about SMARCA5. Here, using ribosomal pull-down for analyzing translated genes in GC B cells, coupled with functional experiments in mice, we identified SMARCA5 as a key chromatin remodeler in B cells. While the naive B cell compartment remained unaffected following conditional depletion of Smarca5, effective proliferation during B cell activation, immunoglobulin class switching, and as a result GC formation and ASC differentiation were impaired. Single-cell multiomic sequencing analyses revealed that SMARCA5 is crucial for facilitating the transcriptional modifications and genomic accessibility of genes that support B cell activation and differentiation. These findings offer novel insights into the functions of SMARCA5, which can be targeted in various human pathologies.

• MeSH
• adenosintrifosfatasy MeSH
• aktivace lymfocytů imunologie   MeSH
• B-lymfocyty * metabolismus   imunologie   MeSH
• buněčná diferenciace * MeSH
• chromozomální proteiny, nehistonové * metabolismus   genetika   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• přesmyk imunoglobulinových tříd genetika   MeSH
• restrukturace chromatinu * MeSH
• zárodečné centrum lymfatické uzliny * imunologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• extrakty z thymu farmakologie   izolace a purifikace   klasifikace   terapeutické užití   MeSH
• thymopentin farmakologie   terapeutické užití   MeSH
• thymopoetiny farmakologie   terapeutické užití   MeSH
• thymosin farmakologie   terapeutické užití   MeSH
• thymové hormony * farmakologie   klasifikace   terapeutické užití   MeSH
• thymus imunologie   metabolismus   MeSH
• Publikační typ
• přehledy MeSH

AIM: The aim of this study was to assess whether the use of sentinel lymph node (SLN) in addition to lymphadenectomy was associated with survival benefit in patients with early-stage cervical cancer. METHODS: International, multicenter, retrospective study. INCLUSION CRITERIA: cervical cancer treated between 01/2007 and 12/2016 by surgery only; squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, FIGO 2009 stage IB1-IIA2, negative surgical margins, and laparotomy approach. Patients undergoing neo-adjuvant and/or adjuvant treatment and/or with positive para-aortic lymph nodes, were excluded. Women with positive pelvic nodes who refused adjuvant treatment, were included. Lymph node assessment was performed by SLN (with ultrastaging protocol) plus pelvic lymphadenectomy ('SLN' group) or pelvic lymphadenectomy alone ('non-SLN' group). RESULTS: 1083 patients were included: 300 (27.7 %) in SLN and 783 (72.3 %) in non-SLN group. 77 (7.1 %) patients had recurrence (N = 11, 3.7 % SLN versus N = 66, 8.4 % non-SLN, p = 0.005) and 34 (3.1 %) (N = 4, 1.3 % SLN versus N = 30, 3.8 % non-SLN, p = 0.033) died. SLN group had better 5-year disease-free survival (DFS) (96.0 %,95 %CI:93.5-98.5 versus 92.0 %,95 %CI:90.0-94.0; p = 0.024). No 5-year overall survival (OS) difference was shown (98.4 %,95 %CI:96.8-99.9 versus 96.8 %,95 %CI:95.4-98.2; p = 0.160). SLN biopsy and lower stage were independent factors associated with improved DFS (HR:0.505,95 %CI:0.266-0.959, p = 0.037 and HR:2.703,95 %CI:1.389-5.261, p = 0.003, respectively). Incidence of pelvic central recurrences was higher in the non-SLN group (1.7 % versus 4.5 %, p = 0.039). CONCLUSION: Adding SLN biopsy to pelvic lymphadenectomy was associated with lower recurrence and death rate and improved 5-year DFS. This might be explained by the lower rate of missed nodal metastasis thanks to the use of SLN ultrastaging. SLN biopsy should be recommended in patients with early-stage cervical cancer.

• MeSH
• biopsie sentinelové lymfatické uzliny metody   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfadenektomie * metody   MeSH
• lymfatické metastázy MeSH
• nádory děložního čípku * patologie   chirurgie   mortalita   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• sentinelová uzlina * patologie   chirurgie   MeSH
• spinocelulární karcinom chirurgie   patologie   mortalita   MeSH
• staging nádorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND: Newborn screening (NBS) programs for severe combined immunodeficiency facilitate early diagnosis of severe combined immunodeficiency and promote early treatment with hematopoietic stem cell transplantation, resulting in improved clinical outcomes. Infants with congenital athymia are also identified through NBS because of severe T-cell lymphopenia. With the expanding introduction of NBS programs, referrals of athymic patients for treatment with thymus transplantation have recently increased at Great Ormond Street Hospital (GOSH) (London, United Kingdom). OBJECTIVE: We studied the impact of NBS on timely diagnosis and treatment of athymic infants with thymus transplantation at GOSH. METHODS: We compared age at referral and complications between athymic infants diagnosed after clinical presentation (n = 25) and infants identified through NBS (n = 19) who were referred for thymus transplantation at GOSH between October 2019 and February 2023. We assessed whether age at time of treatment influences thymic output at 6 and 12 months after transplantation. RESULTS: The infants referred after identification through NBS were significantly younger and had fewer complications, in particular fewer infections. All deaths occurred in the group of those who did not undergo NBS, including 6 patients before and 2 after thymus transplantation because of preexisting infections. In the absence of significant comorbidities or diagnostic uncertainties, timely treatment was achieved more frequently after NBS. Treatment when younger than age 4 months was associated with higher thymic output at 6 and 12 months after transplantation. CONCLUSION: NBS contributes to earlier recognition of congenital athymia, promoting referral of athymic patients for thymus transplantation before they acquire infections or other complications and facilitating treatment at a younger age, thus playing an important role in improving their outcomes.

• MeSH
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• novorozenecký screening MeSH
• syndromy imunologické nedostatečnosti * MeSH
• těžká kombinovaná imunodeficience * diagnóza   terapie   MeSH
• thymus MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH