Assessment of epidemiology and outcomes of adult patients with kidney-limited thrombotic microangiopathies.

Thrombotic microangiopathies (TMA) are usually associated with hematological features (RH-TMA). The epidemiology of TMA limited to kidneys (RL-TMA) is unclear Therefore, patients with TMA and native kidney biopsies were identified during 2009-2022 in 20 French hospitals and results evaluated. RL-TMA was present in 341/757 (45%) patients and associated with lower creatinine levels (median 184 vs 346 µmol/L) than RH-TMA. RL-TMA resulted from virtually all identified causes, more frequently from anti-VEGF treatment and hematological malignancies but less frequently from shigatoxin-associated hemolytic uremic syndrome (HUS), systemic sclerosis, gemcitabine and bacterial infection, and even less frequently when three or more causes/triggers were combined (RL-TMA: 5%; RH-TMA: 12%). RL-TMA was associated with significantly lower major cardiovascular events (10% vs 20%), kidney replacement therapy (23% vs 43%) and death (12% vs 20%) than RH-TMA during follow-up (median 28 months). Atypical HUS (aHUS) was found in 326 patients (RL-TMA: 43%, RH-TMA: 44%). Among the 69 patients with proven complement-mediated aHUS, eculizumab (anti-C5 therapy) was used in 43 (62%) (RL-TMA: 35%; RH-TMA: 71%). Among the 257 other patients with aHUS, including 51% with RL-TMA, eculizumab was used in 29 but with unclear effects of this treatment. Thus, RL-TMA represents a very high proportion of patients with TMA and results from virtually all known causes of TMA and includes 25% of patients with complement-mediated aHUS. Adverse outcomes of RL-TMA are lower compared to RH-TMA but remain significant. Anti-C5 therapy was rarely used in RL-TMA, even in proven complement-mediated aHUS, and its effects remain to be assessed.

Complement Activation and Thrombotic Microangiopathy Associated With Monoclonal Gammopathy: A National French Case Series.

RATIONALE & OBJECTIVE: Hemolytic uremic syndrome (HUS), a thrombotic microangiopathy (TMA) with kidney involvement, is a rare condition in patients with monoclonal gammopathy. In the absence of known causes of TMA, the role of complement activation in endothelial injury in patients with monoclonal gammopathy remains unknown and was the focus of this investigation. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We studied the 24 patients in the French national registry of HUS between 2000 and 2020 who had monoclonal gammopathy without other causes of secondary TMA. We provide the clinical histories and complement studies of these patients. FINDINGS: Monoclonal gammopathy-associated TMA with kidney involvement is estimated to be 10 times less frequent than adult atypical HUS (aHUS) in the French national registry. It is characterized by severe clinical features, with 17 of 24 patients requiring dialysis at disease onset, and with median renal survival of only 20 months. TMA-mediated extrarenal manifestations, particularly cutaneous and neurological involvement, were common and associated with poor overall prognosis. Complement studies identified low C3, normal C4, and high soluble C5b-9 levels in 33%, 100%, and 77% of tested patients, respectively, indicating a contribution of the alternative and terminal complement pathways in the pathophysiology of the disease. Genetic abnormalities in complement genes known to be associated with aHUS were found in only 3 of 17 (17%) who were tested. LIMITATIONS: Retrospective study without comparison group; limited number of patients, limited available blood samples. CONCLUSIONS: Within the spectrum of TMA, TMA associated with monoclonal gammopathy represents a distinct subset. Our findings suggest that HUS associated with monoclonal immunoglobulin is a complement-mediated disease akin to aHUS.

Análise micromorfológica da dentina humana condicionado por primer autocondicionante variando-se a técnica de preparo: ponta diamantada, broca carbide e ponta cvdentus / Micromorphologic analysis of the denting etching human being for primer acidolous variyng preparation technique: diamond tips, dril carbid cvdentus tip

Avaliar, por meio de MEV, o padrão de condicionamento da dentina após a aplicação do primero autocondicionante de um sistema adesivo autocondicionante(Clearfill Liner Bond 2) e do ácido fosfórico à 37 por cento, variando-se o instrumento para preparo. Método: Foram realizados 30 preparos cavitários em 5 molares humanos recém extraídos,sendo 2 preparos com ponta diamantada, 2 preparos com brocas carbide em baixa rotação e 2 preparos com ponta de diamante acionada por ultra-som (para cada dente). Cada dente recebeu um tipo de tratamento: sem condicionamento,condicionamento com ácido fosfórico à 37 porcento por 15s ou aplicação do primer autocondicionante. Os espécimes foram analisados em MEV, onde foram feitas imagens com aumentos de 200, 2000 e 5000 vezes. Resultados: Para os casos preparados com a ponta CVDentus percebemos uma camada de smear com aspecto de flocos além da presença de túbulos dentinários expostos. Nos preparos com ponta diamantadas convencionais e broca carbide o ôsmear layerö apresentou-se mais compacta, com presença de resíduos na dentina intertubular. Conclusão: Por esta análise podemos afirmar que com a utilização das pontas CVDentus mais a aplicação de um primer autocondicionante temos uma camada de ôsmear layerömenos aderida, com um padrão de condicionamento diferente da dentina dos preparos convencionais.

Objective: The proposal at this work is to evaluate, the standard of etching of the dentine after the application of acidulous primer of a self etching adhesive system (Clearfill Liner Bond 2) using SEM. Method: Preparations cavities were done on 5 human molars, as follows: For each tooth, 2 preparations with diamond tip , 2 with drills carbide in low rotation and 2 with CVDentus tip were done; they received a type of treatment: without acid etching, acid etching with acid phosphoric 37% for 15s and application of acidulous primer. The specimens had been analyzed in SEM, where images were enlarged to 200, 2000 and 5000 times. Results: In the cases prepared with CVDentus tip, the smear layer with appearance of flakes, was noticed; in addition to that we also noticed the presence of exposed dentin tubules. On the preparation with diamont tip conventional and drill carbide the smear layer presented a more compacted form. For the cases that CVDentus tip were used, a smear layer with flake aspect was present besides the presence of displayed dentin tubules. In the conventional preparations (diamont tip) smear layer presented residues in dentine intertubular. Conclusion: For this analysis we can affirm that with the use of the CVDentus tip and the application of primer acidulous we have the smear layer less adhered, with a standard of different etching.

Avaliação morfológica de preparos com ponta diamantada, broca carbide e ponta CVDentus / Morphological evaluation of cavities prepared with diamond bur, carbide bur and CVDentus

Este trabalho avaliou, através de microscopia eletrônica de varredura, a superfície dentinária de preparos classe V realizados por pontas diamantadas, brocas carbide e pontas de diamante acionadas por ultra-som (CVDentus), em dentes pré-molares. Os dentes foram preparados em seis situações distintas: preparo com ponta diamantada, broca carbide, ponta diamantada acionada por ultra-som, associado ou não a condicionamento com ácido fosfórico a 37 por cento. Os resultados demonstraram que a superfície dentinária produzida pelas brocas CVDentus apresenta menor quantidade de sujidades e presença de vários túbulos dentinários expostos, porém sem alargamento de sua embocadura. Quando condicionados com ácido fosfórico, apresentaram aspecto semelhante ao dos preparos realizados com os outros instrumentos.