FELIPE LOURENCO LEDESMA
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- Understanding Sabia virus infections (Brazilian mammarenavirus)(2022) NASTRI, Ana Catharina; DUARTE-NETO, Amaro Nunes; CASADIO, Luciana Vilas Boas; SOUZA, William Marciel de; CLARO, Ingra M.; MANULI, Erika R.; SELEGATTO, Gloria; SALOMA, Matias C.; FIALKOVITZ, Gabriel; TABORDA, Mariane; ALMEIDA, Bianca Leal de; MAGRI, Marcello C.; GUEDES, Ana Rubia; NETO, Laura Vieira Perdigao; SATAKI, Fatima Mitie; GUIMARAES, Thais; MENDES-CORREA, Maria Cassia; TOZETTO-MENDOZA, Tania R.; FUMAGALLI, Marcilio Jorge; HO, Yeh-Li; SILVA, Camila ALves Maia da; COLETTI, Thais M.; JESUS, Jacqueline Goes de; ROMANO, Camila M.; HILL, Sarah C.; PYBUS, Oliver; PINHO, Joao Renato Rebello; LEDESMA, Felipe Lourenco; CASAL, Yuri R.; KANAMURA, Cristina; ARAUJO, Leonardo Jose Tadeu de; FERREIRA, Camila Santos da Silva; GUERRA, Juliana Mariotti; FIGUEIREDO, Luiz Tadeu Moraes; DOLHNIKOFF, Marisa; FARIA, Nuno R.; SABINO, Ester C.; AVANCINI, Venacio; ALVES, Ferreira; LEVIN, Anna S.Background: Only two naturally occurring human Sabi ' a virus (SABV) infections have been reported, and those occurred over 20 years ago. Methods: We diagnosed two new cases of SABV infection using metagenomics in patients thought to have severe yellow fever and described new features of histopathological findings. Results: We characterized clinical manifestations, histopathology and analyzed possible nosocomial transmission. Patients presented with hepatitis, bleeding, neurological alterations and died. We traced twenty-nine hospital contacts and evaluated them clinically and by RT-PCR and neutralizing antibodies. Autopsies uncovered unique features on electron microscopy, such as hepatocyte ""pinewood knot"" lesions. Although previous reports with similar New-World arenavirus had nosocomial transmission, our data did not find any case in contact tracing. Conclusions: Although an apparent by rare, Brazilian mammarenavirus infection is an etiology for acute hemorrhagic fever syndrome. The two fatal cases had peculiar histopathological findings not previously described. The virological diagnosis was possible only by contemporary techniques such as metagenomic assays. We found no subsequent infections when we used serological and molecular tests to evaluate close contacts.
- Time to Recurrence as a Prognostic Factor in Parathyroid Carcinoma(2023) MAGNABOSCO, Felipe Ferraz; BRESCIA, Marilia D'Elboux Guimaraes; NASCIMENTO JUNIOR, Climerio Pereira; MASSONI NETO, Ledo Mazzei; ARAP, Sergio Samir; CASTRO JUNIOR, Gilberto de; LEDESMA, Felipe Lourenco; ALVES, Venancio Avancini Ferreira; KOWALSKI, Luiz Paulo; MARTIN, Regina Matsunaga; MONTENEGRO, Fabio Luiz de MenezesBackground Parathyroid carcinoma (PC) is a rare and challenging disease without clearly understood prognostic factors. Adequate management can improve outcomes. Characteristics of patients treated for PC over time and factors affecting prognosis were analyzed. Methods Retrospective cohort study including surgically treated patients for PC between 2000 and 2021. If malignancy was suspected, free-margin resection was performed. Demographic, clinical, laboratory, surgical, pathological, and follow-up characteristics were assessed. Results Seventeen patients were included. Mean tumor size was 32.5 mm, with 64.7% staged as pT1/pT2. None had lymph node involvement at admission, and 2 had distant metastases. Parathyroidectomy with ipsilateral thyroidectomy was performed in 82.2%. Mean postoperative calcium levels were different between patients who developed recurrence vs those who did not (P = .03). Six patients (40%) had no recurrence during follow-up, 2 (13.3%) only regional, 3 (20%) only distant, and 4 (26.6%) both regional and distant. At 5 and 10 years, 79% and 56% of patients were alive, respectively. Median disease-free survival was 70 months. Neither Tumor, Nodule, Metastasis system nor largest tumor dimension (P = .29 and P = .74, respectively) were predictive of death. En bloc resection was not superior to other surgical modalities (P = .97). Time between initial treatment and development of recurrence negatively impacted overall survival rate at 36 months (P = .01). Conclusion Patients with PC can survive for decades and have indolent disease course. Free margins seem to be the most important factor in initial surgery. Recurrence was common (60%), but patients with disease recurrence within 36 months of initial surgery had a lower survival rate.
- Understanding yellow fever-associated myocardial injury: an autopsy study(2023) GIUGNI, Fernando Rabioglio; DEMARCHIAIELLO, Vera; FARIA, Caroline Silverio; POUR, Shahab Zaki; CUNHA, Marielton dos Passos; GIUGNI, Melina Valdo; PINESI, Henrique Trombini; LEDESMA, Felipe Lourenco; MORAIS, Carolina Esteves; HO, Yeh-Li; SZTAJNBOK, Jaques; FERNEZLIAN, Sandra de Morais; SILVA, Luiz Fernando Ferraz da; MAUAD, Thais; ALVES, Venancio Avancini Ferreira; SALDIVA, Paulo Hilario do Nascimento; ANTONANGELO, Leila; DOLHNIKOFF, Marisa; DUARTE-NETO, Amaro NunesBackground Yellow fever (YF) is a viral hemorrhagic fever, endemic in parts of South America and Africa. There is scarce evidence about the pathogenesis of the myocardial injury. The objective of this study is to evaluate the cardiac pathology in fatal cases of YF.Methods This retrospective autopsy study included cases from the Sao Paulo (Brazil) epidemic of 2017-2019. We reviewed medical records and performed cardiac tissue histopathological evaluation, electron microscopy, immunohistochemical assays, RT-qPCR for YF virus (YFV)-RNA, and proteomics analysis on inflammatory and endothelial biomarkers.Findings Seventy-three confirmed YF cases with a median age of 48 (34-60) years were included. We observed myocardial fibrosis in 68 (93.2%) patients; cardiomyocyte hypertrophy in 68 (93.2%); endothelial alterations in 67 (91.8%); fiber necrosis in 50 (68.5%); viral myocarditis in 9 (12.3%); and secondary myocarditis in 5 (6.8%). Four out of five patients with 17DD vaccine-associated viscerotropic disease presented with myocarditis. The cardiac conduction system showed edema, hemorrhages and endothelial fibrinoid necrosis. Immunohistochemistry detected CD68-positive inflammatory interstitial cells and YFV antigens in endothelial and inflammatory cells. YFV-RNA was detected positive in 95.7% of the cardiac samples. The proteomics analysis demonstrated that YF patients had higher levels of multiple inflammatory and endothelial biomarkers in comparison to cardiovascular controls, and higher levels of interferon gamma-induced protein 10 (IP-10) in comparison to sepsis (p = 0.01) and cardiovascular controls (p < 0.001) in Dunn test.Interpretation Myocardial injury is frequent in severe YF, due to multifactorial mechanisms, including direct YFV-mediated damage, endothelial cell injury, and inflammatory response, with a possible prominent role for IP-10.
- Bevacizumab-Associated Thrombotic Microangiopathy Treated with Eculizumab: A Case Report(2023) PADILHA, Wallace Stwart Carvalho; CESAR, Bruno Nogueira; PACHECO, Samara Theodoro; SOUSA, Alessandra Alves De; LEDESMA, Felipe Lourenco; MALHEIROS, Denise Maria Avancini Costa; TEIXEIRA, Marcela Crosara AlvesPatient: Female, 64-year-old Final Diagnosis: Bevacizumab-associated thrombotic microangiopathy Symptoms: Microangiopathic hemolytic anemia and acute kidney injury Clinical Procedure: - Specialty: Nephrology Objective: Rare disease Background: Bevacizumab is an approved targeted therapy for metastatic cancer treatment. It can have adverse effects on multiple organs. Despite its low incidence, thrombotic microangiopathy (TMA) is the most severe complication. TMA has been associated with complement dysregulation, and treatment with eculizumab can be effective, despite the paucity of literature on eculizumab therapy for bevacizumab-associated TMA. To date, 10 cases have been reported, with less than half of them including a kidney biopsy. We present a new case of bevacizumab-associated TMA successfully treated with eculizumab, along with kidney biopsy records and an overview of mechanisms underlying TMA development in bevacizumab-treated patients. Case Report: A female patient diagnosed with metastatic breast cancer who was treated with bevacizumab in conjunction with chemotherapy was admitted to the hospital for acute kidney injury requiring hemodialysis, microangiopathic hemolytic anemia, and thrombocytopenia. TMA was diagnosed and was later confirmed by a kidney biopsy. Primary causes for TMA, such as ADAMTS13 deficiency and shiga toxin associated hemolytic-uremic syndrome, were ruled out, and the patient's condition was ultimately found to be triggered by exposure to bevacizumab. After discontinuing bevacizumab and receiving 4 weekly doses of eculizumab, kidney function and hematological parameters improved. Conclusions: Bevacizumab-associated TMA can be reversed or attenuated in some patients with the use of eculizumab (inhibiting complement system overactivation), possibly reducing time to recovery, with fewer long-term sequelae. This additional case encourages future clinical trials to evaluate the safety and efficacy of eculizumab in cases of TMA associated with bevacizumab.
- Bilateral Wilms' tumor in a child with Denys-Drash syndrome: novel frameshift variant disrupts the WT1 nuclear location signaling region(2022) GUARAGNA, Mara Sanches; LEDESMA, Felipe Lourenco; MANZANO, Victoria Zavanelli; MACIEL-GUERRA, Andrea Trevas; GUERRA-JUNIOR, Gil; SILVA, Marcelo Milone; BRITO, Pedro Luiz de; MELLO, Maricilda Palandi deBackground Wilm's Tumor (WT) is the most common pediatric kidney cancer. Whereas most WTs are isolated, approximately 5% are associated with syndromes such as Denys-Drash (DDS), characterized by early onset nephropathy, disorders of sex development and predisposition to WT. Case presentation A 46,XY patient presenting with bilateral WT and genital ambiguity without nephropathy was heterozygous for the novel c.851_854dup variant in WT1 gene sequence. This variant affects the protein generating the frameshift p.(Ser285Argfs*14) that disrupts a nuclear localization signal (NLS) region. Conclusions This molecular finding is compatible with the severe scenario regarding the Wilm's tumor presented by the patient even though nephropathy was absent.
- Evaluation of glomerular sirtuin-1 and claudin-1 in the pathophysiology of nondiabetic focal segmental glomerulosclerosis(2023) LOPES-GONCALVES, Guilherme; COSTA-PESSOA, Juliana Martins; PIMENTA, Ruan; TOSTES, Ana Flavia; SILVA, Eloisa Martins da; LEDESMA, Felipe Lourenco; MALHEIROS, Denise Maria Avancini Costa; ZATZ, Roberto; THIEME, Karina; CAMARA, Niels Olsen Saraiva; OLIVEIRA-SOUZA, MariaFocal segmental glomerulosclerosis (FSGS) is the leading cause of nephrotic syndrome, which is characterized by podocyte injury. Given that the pathophysiology of nondiabetic glomerulosclerosis is poorly understood and targeted therapies to prevent glomerular disease are lacking, we decided to investigate the tight junction protein claudin-1 and the histone deacetylase sirtuin-1 (SIRT1), which are known to be involved in podocyte injury. For this purpose, we first examined SIRT1, claudin-1 and podocin expression in kidney biopsies from patients diagnosed with nondiabetic FSGS and found that upregulation of glomerular claudin-1 accompanies a significant reduction in glomerular SIRT1 and podocin levels. From this, we investigated whether a small molecule activator of SIRT1, SRT1720, could delay the onset of FSGS in an animal model of adriamycin (ADR)-induced nephropathy; 14 days of treatment with SRT1720 attenuated glomerulosclerosis progression and albuminuria, prevented transcription factor Wilms tumor 1 (WT1) downregulation and increased glomerular claudin-1 in the ADR + SRT1720 group. Thus, we evaluated the effect of ADR and/or SRT1720 in cultured mouse podocytes. The results showed that ADR [1 mu M] triggered an increase in claudin-1 expression after 30 min, and this effect was attenuated by pretreatment of podocytes with SRT1720 [5 mu M]. ADR [1 mu M] also led to changes in the localization of SIRT1 and claudin-1 in these cells, which could be associated with podocyte injury. Although the use of specific agonists such as SRT1720 presents some benefits in glomerular function, their underlying mechanisms still need to be further explored for therapeutic use. Taken together, our data indicate that SIRT1 and claudin-1 are relevant for the pathophysiology of nondiabetic FSGS.