ADHEMAR LONGATTO FILHO
Projetos de Pesquisa
Unidades Organizacionais
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
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- Inflammation Is a Histological Characteristic of Skeletal Muscle in Chronic Limb Threatening Ischemia(2024) FERREIRA, Joana; AFONSO, Julieta; LONGATTO-FILHO, Adhemar; ROQUE, Susana; CARNEIRO, Alexandre; VILE, Isabel; SILVA, Cristina; CUNHA, Cristina; MESQUITA, Amilcar; COTTER, Jorge; CORREIA-NEVES, Margarida; MANSILHA, Armando; CUNHA, PedroBackground: The loss of skeletal muscle is a prognostic factor in several diseases including in patients with chronic limb threatening ischemia (CLTI). Patients with CLTI also have a lower skeletal mass and area when compared to those with claudication. However, there are no currently available data regarding the histological characteristics of core muscles in patients with CLTI. This study aims to determine the differences in core skeletal muscles between patients with claudication and those with CLTI. The second aim is to evaluate the differences in myokines, which are molecules secreted by skeletal muscle, between patients with claudication and those with CLTI. Methods: An observational, prospective study was conducted from January 2018 to July 2022 involving consecutive patients with peripheral arterial disease (PAD). The clinical characteristics were registered. In PAD patients with surgical indication for common femoral artery approach, samples of sartorius skeletal muscle (and not from the limb muscles directly involved in the ischemic process) were collected. The samples were submitted to histological characterization on hematoxylin-eosin and to immunohistochemical analysis to detect CD45+ leukocytes and CD163+ macrophages. The extent of the inflammatory cells (leukocytes and macrophages) was semiquantitatively assessed using a 0 -to -4 grade scale as follows: absent (0t), mild (t), moderate (tt), severe (ttt), and very severe (tttt). Serum levels of myokines: irisin, myostatin, IL -8, and lL-6 were determined with multiplex bead -based immunoassay. Results: 119 patients (mean age: 67.58 +/- 9.60 years old, 79.80% males) 64 with claudication and 54 with CLTI were enrolled in the study. No differences were registered between patients with claudication and those with CLTI on age, gender, cardiovascular risk factors, and medication, except on smoking habits. There was a significantly higher prevalence of smokers and a higher smoking load in the claudication group. Samples of sartorius skeletal muscle from 40 patients (14 with claudication and 26 with CLTI) were submitted to histological analysis. No differences were found in skeletal muscle fibers preservation, trauma, or hemorrhage (on hematoxylin-eosin staining). However, in the immunohistochemistry study, we found more inflammatory cells CD45+ leukocytes in patients with CLTI when compared to those with claudication [CD45+ > moderate (tt): claudication (n = 14): 4; 28.57%; CLTI (n = 25): 16; 64.00%; P = 0.034]. Patients with CLTI also had higher tissue levels of CD163+ macrophages, but this difference was not significant [CD163+ > moderate (tt): claudication (n = 13): 7; 53.85%; CLTI (n = 27): 21; 77.78%; P = 0.122]. The serum levels of the myokines, irisin, and myostatin were below the lower limit of detection, in the majority of patients, so no valid results were obtained. However, patients with CLTI had a higher serum level of Interleukin (IL) -6 and IL -8. Conclusions: CLTI patients exhibit increased quantities of leukocytes in their sartorius muscle, as well as elevated serum levels of myokines IL -8 and IL -6. Inflamed skeletal muscle can contribute to the loss of muscle mass and account for the lower density of skeletal muscle observed in CLTI. Additionally, inflamed skeletal muscle may contribute to the development of systemic inflammation through the secretion of pro -inflammatory cytokines into the systemic circulation. Halting the inflammatory process could eventually improve the prognosis of CLTI patients.
- Peri-Carotid Adipose Tissue and Atherosclerosis at Carotid Bifurcation(2024) FERREIRA, Joana; LONGATTO-FILHO, Adhemar; DIONISIO, Ana; CORREIA-NEVES, Margarida; CUNHA, Pedro; MANSILHA, ArmandoVulnerable carotid plaques are responsible for 20% of the ischemic strokes. The identification of these asymptomatic carotid plaques that will become symptomatic is essential but remains unclear. Our main goal was to investigate whether the amount of the peri-carotid adipose tissue, estimated by the extra-media thickness (EMT), is associated with the atherosclerotic characteristics at the carotid bifurcation in patients with PAD. An observational, prospective, single-center, longitudinal study was conducted. Overall, 177 patients were subjected to carotid Doppler ultrasound at the study admission. The following data were collected: EMT, intima-media thickness (IMT), the presence of carotid plaques, the area of the highest plaque, the presence of ""acute culprit"" carotid stenosis, and the grade of internal carotid stenosis. ""Acute culprit"" carotid stenosis was defined as a significant atherosclerotic plaque that leads to a neurologic event within 15 days. From each carotid bifurcation, a right and a left EMT were determined. We analyzed both the mean EMTs (calculated as the mean between the right and the left EMT) and the EMT ipsilateral to the carotid bifurcation. The presence of carotid plaques was associated with a higher mean EMT [Median = 1.14; IQR = 0.66 versus Median = 0.97; IQR = 0.40; p = 0.001]. A positive correlation was found between the mean EMT and IMT (right: rho = 0.20; p = 0.010; left: rho = 0.21; p = 0.007) and between the mean EMT and the area of the largest carotid plaque (right: rho = 0.17; p = 0.036; left: rho = 0.22; p = 0.004). Left carotid stenosis >= 70% was associated with higher ipsilateral EMT [Median = 1.56; IQR = 0.70 versus Median = 0.94; IQR = 0.42; p = 0.009]. Patients with ""acute culprit"" carotid stenosis had a higher ipsilateral EMT [left ipsilateral EMT: Median = 1.46; IQR = 0.63; ""non-acute"": Median = 0.94; IQR = 0.43; p = 0.009; right ipsilateral EMT: Median = 2.25; IQR = 0.62; ""non-acute"": Median = 1.00; IQR = 0.51; p = 0.015]. This difference was not found in the contra-lateral EMT. Six months after the neurologic event, EMT ipsilateral to an ""acute culprit"" carotid stenosis decreased (p = 0.036). The amount of peri-carotid adipose tissue, estimated with EMT, was associated with atherosclerosis at the carotid arteries. The mean EMT was associated with the features of chronic atherosclerosis lesions: the presence of carotid plaques, IMT, and the area of the highest plaque. Ipsilateral EMT was linked with ""acute culprit"" atherosclerotic plaque.
- The Role of Pelvic Exenteration in Cervical Cancer: A Review of the Literature(2024) UBINHA, Ana Carla Franco; PEDRAO, Priscila Grecca; TADINI, Aline Cassia; SCHMIDT, Ronaldo Luis; SANTOS, Marcelo Henrique dos; ANDRADE, Carlos Eduardo Mattos da Cunha; LONGATTO FILHO, Adhemar; REIS, Ricardo dosSimple Summary Cervical cancer ranks as the fourth most common malignant neoplasm among women worldwide. In low-income countries, the diagnosis usually occurs at advanced stages, with the recommendation of chemoradiotherapy. When this initial approach fails, with persistent disease or even in the context of tumor recurrence, pelvic exenteration (PE) becomes a therapeutic option to be considered. The criteria for recommending PE have evolved over time, influenced by advancements in surgical techniques and perioperative care. These developments have enhanced the capacity for extended resections and expanded treatment possibilities for patients who were previously limited to palliative measures. Through this review, we aim to provide insights and tools to facilitate the identification of patients who may benefit from such a complex procedure.Abstract Pelvic exenteration represents a radical procedure aimed at achieving complete tumor resection with negative margins. Although it is the only therapeutic option for some cases of advanced tumors, it is associated with several perioperative complications. We believe that careful patient selection is related to better oncologic outcomes and lower complication rates. The objectives of this review are to identify the most current indications for this intervention, suggest criteria for case selection, evaluate recommendations for perioperative care, and review oncologic outcomes and potential associated complications. To this end, an analysis of English language articles in PubMed was performed, searching for topics such as the indication for pelvic exenteration for recurrent gynecologic neoplasms selection of oncologic cases, the impact of tumor size and extent on oncologic outcomes, preoperative and postoperative surgical management, surgical complications, and outcomes of overall survival and recurrence-free survival.