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1.
Nutr Hosp ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39037198

RESUMO

BACKGROUND: muscle mass (MM) plays an important role in the physical function of hemodialysis patients; however, muscle mass measurement can be unreliable and expensive. In contrast, the measurement of physical function (PF) is simple and inexpensive and may serve as an alternative. The aim of this study was to correlate the measurement of MM by computed tomography (CT) with physical function measurements and physical activity (PA) levels in HD patients. METHODS: this was a cross-sectional study that included 38 HD patients from a single HD clinic. Each participant had a CT scan to measure mid-thigh muscle mass. Physical function tests were assessed using the six-minute walk test (SMWT), handgrip strength (HGS) test, 5 x sit-to-stand test (STS5), timed up and go test (TUGT) and Short Physical Performance Battery (SPPB), while physical activity levels were measured using the Godin-Shephard leisure-time physical activity questionnaire. Correlation analysis was used to examine the relationship between variables. RESULTS: handgrip strength was strongly positively correlated with thigh muscle area (r = 0.656, p ≤ 0.001) and weakly correlated with arm muscle area (r = 0.396, p = 0.002), SMWT (r = 0.373, p = 0.004), SPPB (r = 0.269, p = 0.041) and physical activity (r = 0.323, p = 0.013). There was also a trend for an inverse correlation between handgrip strenght and TUGT (r = -0.235, p = 0.076). Positive correlations were found between the thigh muscle area and the SPPB (r = 0.339, p = 0.009) and PA (r = 0.293, p = 0.025), while there was a trend for an inverse correlation between thigh muscle area and STS5 (r = -0.256, p = 0.052). CONCLUSION: several measures of PF and strenght were correlated with objectives measurements of MM, thus provide options for low-cost measurements related to muscle mass.

3.
J Hand Surg Glob Online ; 6(3): 303-307, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38817758

RESUMO

Purpose: The purpose of this study was to gauge whether patients with preexisting mental health conditions have desirable outcomes when undergoing wide-awake local anesthesia with no tourniquet (WALANT) hand surgery. Methods: A retrospective review of 133 patients who underwent WALANT surgery by 2 senior authors from August 2019 to October 2020 was performed. Patients were administered a 10-question postoperative survey detailing perioperative pain, experience, and satisfaction concerning their procedure. Analysis was performed for patient responses to the questionnaire, demographics, comorbidities, and patient-reported outcomes using the Single Assessment Numeric Evaluation (SANE). Results: There were 61 patients identified as having a preexisting psychiatric diagnosis compared to 70 patients without who underwent WALANT surgery. Comparing psychiatric diagnosis and nonpsychiatric diagnosis cohorts, there was no significant difference in preoperative anxiety (3.75 vs 3.30), pain during procedure (0.67 vs 0.56), or pain after surgery (4.89 vs 4.26). There was a significantly higher pain score with preoperative injection in the psychiatric diagnosis cohort (4.07 vs 2.93). When asked if they would have a WALANT procedure again, 95.1% of patients in the psychiatric diagnosis cohort and 98.6% of patients in the nonpsychiatric diagnosis group said they would. There was no significant difference in average preoperative SANE scores (59.67 [no psych diagnosis] vs 61.70 [psych diagnosis]) or postoperative SANE scores (82.82 [no psych diagnosis] vs 81.06 [psych diagnosis]) between the two cohorts. Conclusions: WALANT surgery was nearly as well tolerated in patients with a preexisting mental health diagnosis when compared to those without a preexisting diagnosis. Clinical Relevance: Surgeons who are currently or potentially performing WALANT surgery should not rule out patients as eligible candidates because of a prior diagnosis of a mental health condition.

4.
Sci Rep ; 14(1): 10583, 2024 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719848

RESUMO

Identifying marker combinations for robust prognostic validation in primary tumour compartments remains challenging. We aimed to assess the prognostic significance of CSC markers (ALDH1, CD44, p75NTR, BMI-1) and E-cadherin biomarkers in OSCC. We analysed 94 primary OSCC and 67 metastatic lymph node samples, including central and invasive tumour fronts (ITF), along with clinicopathological data. We observed an increase in ALDH1+/CD44+/BMI-1- tumour cells in metastatic lesions compared to primary tumours. Multivariate analysis highlighted that elevated p75NTR levels (at ITF) and reduced E-cadherin expression (at the tumour centre) independently predicted metastasis, whilst ALDH1high exhibited independent predictive lower survival at the ITF, surpassing the efficacy of traditional tumour staging. Then, specifically at the ITF, profiles characterized by CSChighE-cadherinlow (ALDH1highp75NTRhighE-cadherinlow) and CSCintermediateE-cadherinlow (ALDH1 or p75NTRhighE-cadherinlow) were significantly associated with worsened overall survival and increased likelihood of metastasis in OSCC patients. In summary, our study revealed diverse tumour cell profiles in OSCC tissues, with varying CSC and E-cadherin marker patterns across primary tumours and metastatic sites. Given the pivotal role of reduced survival rates as an indicator of unfavourable prognosis, the immunohistochemistry profile identified as CSChighE-cadherinlow at the ITF of primary tumours, emerges as a preferred prognostic marker closely linked to adverse outcomes in OSCC.


Assuntos
Família Aldeído Desidrogenase 1 , Biomarcadores Tumorais , Caderinas , Carcinoma de Células Escamosas , Neoplasias Bucais , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Família Aldeído Desidrogenase 1/metabolismo , Biomarcadores Tumorais/metabolismo , Caderinas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Receptores de Hialuronatos/metabolismo , Imuno-Histoquímica , Metástase Linfática , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/mortalidade , Neoplasias Bucais/diagnóstico , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proteínas do Tecido Nervoso/metabolismo , Complexo Repressor Polycomb 1/metabolismo , Complexo Repressor Polycomb 1/genética , Prognóstico , Receptores de Fator de Crescimento Neural/metabolismo , Retinal Desidrogenase/metabolismo
5.
Neurosurgery ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501815

RESUMO

BACKGROUND AND OBJECTIVES: Moyamoya disease (MMD) is a chronic steno-occlusive disease of the intracranial circulation that depends on neoangiogenesis of collateral vessels to maintain cerebral perfusion and is primarily managed with cerebral revascularization surgery. A quantitative assessment of preoperative and postoperative collateral flow using quantitative magnetic resonance angiography with noninvasive optimal vessel analysis (NOVA) was used to illustrate the impact of revascularization on cerebral flow distribution. METHODS: A retrospective review of patients with unilateral MMD who underwent direct, indirect, or combined direct/indirect cerebral revascularization surgery was conducted between 2011 and 2020. Using NOVA, flow was measured at the anterior cerebral artery (ACA), ACA distal to the anterior communicating artery (A2), middle cerebral artery (MCA), posterior cerebral artery (PCA), and PCA distal to the posterior communicating artery (P2). Pial flow (A2 + P2) and collateral flow (ipsilateral [A2 + P2])-(contralateral [A2 + P2]) were measured and compared before and after revascularization surgery. Total hemispheric flow (MCA + A2 + P2) with the addition of the bypass graft flow postoperatively was likewise measured. RESULTS: Thirty-four patients with unilateral MMD underwent cerebral revascularization. Median collateral flow significantly decreased from 68 to 39.5 mL/min (P = .007) after bypass. Hemispheres with maintained measurable bypass signal on postoperative NOVA demonstrated significant reduction in median collateral flow after bypass (P = .002). Median total hemispheric flow significantly increased from 227 mL/min to 247 mL/min (P = .007) after bypass. Only one patient suffered an ipsilateral ischemic stroke, and no patients suffered a hemorrhage during follow-up. CONCLUSION: NOVA measurements demonstrate a reduction in pial collateral flow and an increase in total hemispheric flow after bypass for MMD, likely representing a decrease in leptomeningeal collateral stress on the distal ACA and PCA territories. Further studies with these measures in larger cohorts may elucidate a role for NOVA in predicting the risk of ischemic and hemorrhagic events in MMD.

6.
Case Rep Nephrol Dial ; 14(1): 48-55, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38524730

RESUMO

Introduction: The presence of three different entities in a single patient is usually of clinical interest and mostly anecdotal. The overlap of systemic sclerosis (SSc), Sjögren syndrome (SS), and ANCA-associated renal-limited vasculitis has been reported only once previously. Case Presentation: A 61-year-old female was evaluated at consultation with 2 years of symptomatology, presenting cardboard-like skin, sclerodactyly, limited oral opening, and dry skin and eyes. She was admitted for progressive renal failure (serum creatinine, 5.5 mg/dL). Her serology work-up showed positive anti-SCL-70, anti-Ro, anti-La, anti-MPO, and antinuclear antibodies. Renal biopsy was performed and confirmed histological findings for SSc, SS, and ANCA-associated vasculitis with active extracapillary glomerulonephritis with fibrous predominance (EUVAS-Berden sclerotic class), active tubulointerstitial nephritis, focal tubular injury, and moderate chronic arteriolopathy. Treatment with 6 monthly doses of methylprednisolone and cyclophosphamide was established. At the last follow-up, the patient maintained a stable serum creatinine level of 2.6 mg/dL and had decreased proteinuria, no erythrocyturia, and no requirement for renal replacement therapy. Conclusion: Systemic sclerosis is a rare autoimmune disease; nevertheless, overlap with Sjögren syndrome is relatively common, although its association with ANCA vasculitis is anecdotal. Diagnostic integration presents a challenge for nephrologists to define the prognosis and a specific treatment.

7.
J Biomed Mater Res B Appl Biomater ; 112(1): e35340, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37929804

RESUMO

Effective bone substitute biomaterials remain an important challenge in patients with large bone defects. Glass ceramics produced by different synthesis routes may result in changes in the material physicochemical properties and consequently affect the success or failure of the bone healing response. To investigate the differences in the orchestration of the inflammatory and healing process in bone grafting and repair using different glass-ceramic routes production. Thirty male Wistar rats underwent surgical unilateral parietal defects filled with silicate glass-ceramic produced by distinct routes: BS - particulate glass-ceramic produced via the fusion/solidification route, and BG - particulate glass-ceramic produced via the sol-gel route. After 7, 14, and 21 days from biomaterial grafting, parietal bones were removed to be analyzed under H&E and Massons' Trichome staining, and immunohistochemistry for CD206, iNOS, and TGF-ß. Our findings demonstrated that the density of lymphocytes and plasma cells was significantly higher in the BS group at 45, and 7 days compared to the BG group, respectively. Furthermore, a significant increase of foreign body giant cells (FBGCs) in the BG group at day 7, compared to BS was found, demonstrating early efficient recruitment of FBGCs against sol-gel-derived glass-ceramic particulate (BS group). According to macrophage profiles, CD206+ macrophages enhanced at the final periods of both groups, being significantly higher at 45 days of BS compared to the BG group. On the other hand, the density of transformation growth factor beta (TGF-ß) positive cells on 21 days were the highest in BG, and the lowest in the BS group, demonstrating a differential synergy among groups. Noteworthy, TGF-ß+ cells were significantly higher at 21 days of BG compared to the BS group. Glass-ceramic biomaterials can act differently in the biological process of bone remodeling due to their route production, being the sol-gel route more efficient to activate M2 macrophages and specific FBGCs compared to the traditional route. Altogether, these features lead to a better understanding of the effectiveness of inflammatory response for biomaterial degradation and provide new insights for further preclinical and clinical studies involved in bone healing.


Assuntos
Materiais Biocompatíveis , Substitutos Ósseos , Humanos , Ratos , Animais , Masculino , Teste de Materiais , Ratos Wistar , Materiais Biocompatíveis/química , Regeneração Óssea , Substitutos Ósseos/química , Cerâmica/farmacologia , Cerâmica/química , Macrófagos , Fator de Crescimento Transformador beta , Vidro/química
8.
J Neurosurg ; 140(2): 450-462, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37877963

RESUMO

OBJECTIVE: Direct cerebral revascularization is considered as one of the most technically challenging operations in neurosurgery. Technical errors are often not identified during the case, but only after the recirculation stage, making management crucial at that time of the procedure. In this study, the authors sought to describe troubleshooting of the technical errors encountered in initially failed bypass cases. METHODS: A retrospective analysis describing a single-surgeon, single-institution experience between 2014 and 2021 was performed, based on operative reports and videos, including a 30-day follow-up period. Initially failed bypass was defined if the bypass was not patent or had a significant leak after recirculation, irrespective of the final result. RESULTS: One hundred thirty-eight bypass cases were reviewed for complex aneurysms (n = 49), moyamoya disease (n = 59), and atherosclerosis (n = 30). Fifty-one initially failed anastomoses were identified; 43 of these were the result of a technical error. Etiologies of these failed anastomoses included a clot (n = 14), vessel kinking (n = 4), spasm (n = 5), suture-related cause (n = 5), inappropriate donor or recipient (n = 3), or lack of demand (n = 8). A major leak was attributed to an uncoagulated side branch (n = 4), vessel injury due to suture/clip placement (n = 1), or inadequate suture line coverage (n = 7). Thirty-seven (86%) of 43 cases were troubleshot successfully, as salvage maneuvers included papaverine vessel massage, donor repositioning, re-anastomosis for occlusion in select cases, local hemostatic agents, and suturing or coagulating side branches in a leak. Thirty-day follow-up revealed similar rates of patency between successfully troubleshot patients (35/37) and the rest of the cases (80/87, p = 0.6). CONCLUSIONS: Three major patterns of a noncompatible bypass were found: a major leak, an acute occlusion, or a delayed occlusion. Based on the authors' experience, salvage strategies proved successful, showing an eventual high patency rate. The authors suggest a gradual, structured algorithm to address this stage in surgery that may contribute specifically to cerebrovascular neurosurgeons at the beginning of their careers.


Assuntos
Revascularização Cerebral , Aneurisma Intracraniano , Doença de Moyamoya , Humanos , Revascularização Cerebral/métodos , Estudos Retrospectivos , Doença de Moyamoya/cirurgia , Aneurisma Intracraniano/cirurgia , Anastomose Cirúrgica/métodos
9.
Cytokine ; 174: 156455, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38043142

RESUMO

BACKGROUND: Natural killer (NK) cells are one of the most crucial immune cells that mediate the antitumoral response due to their ability to immediately recognize and eliminate transformed cells. Because of their great cytotoxic activity, the function of NK cells must be robustly regulated to avoid tissue damage. Such regulation is mediated by a coordinated engagement of activating (NKp46) and inhibitory (CD158b) receptors, which tumor cells may use to escape from immunosurveillance. Also, NK cells are generally divided based on surface molecules, such as CD16 and CD56, and can be classified as CD56brightCD16- (regulatory) and CD56dimCD16+ (cytotoxic) NK cells. Here, we aimed to evaluate the frequency and phenotype of circulating NK cells in patients with advanced carcinomas, as well as their systemic cytokine/chemokine and growth factors production. METHODS: Peripheral blood was collected from 24 patients with advanced solid cancer during or after treatment and from 10 healthy donors. The frequency and the expression of activating (NKp46) and inhibitory (CD158b) molecules of CD56brightCD16- and CD56dimCD16+ NK cells were assessed by flow cytometry and the multiplex Luminex platform was used to quantify the secreted factors in peripheral blood serum. RESULTS: Cancer patients had a lower frequency of the cytotoxic CD56dim CD16+ NK cells subset in comparison with healthy controls. Also, the regulatory CD56bright CD16- NKs isolated from cancer patients exhibited a significantly lower expression of NKp46. Among 29 immunological and growth factors analyzed in the peripheral blood of oncologic patients, MCP-1, IP-10, and eotaxin, and VEGF they have presented a higher proportion. The Pearson correlation test showed that IL-12p40 positively correlates with CD56brightCD16- NK cells. We also observed a positive correlation between MCP-1 and the activating marker NKp46, as well as a negative correlation between IP-10 and TNF-α and NKp46. CD158b expression in CD56dimCD16+ was positively correlated with EGF and negatively correlated with MIP-1ß. CONCLUSIONS: Taken together, these results suggest that cancer patients present a shift towards a poorly cytotoxic and less activated NK profile which may contribute to tumor development and progression. The understanding of NK cell biology and soluble factors during tumor development could aid in the design of possible targeting therapeutic approaches.


Assuntos
Carcinoma , Citocinas , Humanos , Citocinas/metabolismo , Quimiocina CXCL10/metabolismo , Células Matadoras Naturais , Citometria de Fluxo , Carcinoma/metabolismo , Antígeno CD56/metabolismo , Receptores de IgG/metabolismo
10.
J Am Acad Dermatol ; 90(1): 66-73, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37704106

RESUMO

BACKGROUND: Evidence regarding long-term therapeutic outcomes and disease-specific survival (DSS) in Extramammary Paget's disease (EMPD) is limited. OBJECTIVES: To assess the DSS and outcomes of surgical and nonsurgical therapeutic modalities in a large cohort of EMPD patients. METHODS: Retrospective chart review of EMPD patients from 20 Spanish tertiary care hospitals. RESULTS: Data on 249 patients with a median follow-up of 60 months were analyzed. The estimated 5-, 10-, and 15-year DSS was 95.9%, 92.9%, and 88.5%, respectively. A significantly lower DSS was observed in patients showing deep dermal invasion (≥1 mm) or metastatic disease (P < .05). A ≥50% reduction in EMPD lesion size was achieved in 100% and 75.3% of patients treated with surgery and topical therapies, respectively. Tumor-free resection margins were obtained in 42.4% of the patients after wide local excision (WLE). The 5-year recurrence-free survival after Mohs micrographic surgery (MMS), WLE with tumor-free margins, WLE with positive margins, radiotherapy, and topical treatments was 63.0%, 51.4%, 20.4%, 30.1%, and 20.8%, respectively. LIMITATIONS: Retrospective design. CONCLUSIONS: EMPD is usually a chronic condition with favorable prognosis. MMS represents the therapeutic alternative with the greatest efficacy for the disease. Recurrence rates in patients with positive margins after WLE are similar to the ones observed in patients treated with topical agents.


Assuntos
Doença de Paget Extramamária , Humanos , Estudos Retrospectivos , Doença de Paget Extramamária/cirurgia , Cirurgia de Mohs , Análise de Sobrevida , Margens de Excisão , Resultado do Tratamento , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/terapia , Recidiva Local de Neoplasia/patologia
12.
J Appl Oral Sci ; 31: e20230227, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38126564

RESUMO

BACKGROUND: Lip squamous cell carcinoma (LSCC) accounts for 12% of all head and neck cancers. It is caused by chronic exposure to ultraviolet light solar radiation and related to previous actinic cheilitis (AC). This study aimed to investigate the immunostaining of the putative cancer stem cells (CSC) markers ALDH1 and CD44 in AC (n=30) and LSCC (n=20). ALDH1 positivity was found to be statistically higher in LSCC than in AC lesions (p=0.0045), whilst CD44 expression was statistically higher in AC than in LSCC lesions (p=0.0155). ALDH1+ cells in AC lesions were associated with specific clinical features: a younger age (<60 years old), the female gender, white skin, not smoking or consuming alcohol, and a fast evolution, and not associated with the chronic exposure to UV radiation (p<0.0001). CD44 positivity was associated with patients who were male, feoderm, smoked, consumed alcohol, underwent occupational exposure to UV-radiation, and demonstrated lesions with log-time evolution (p<0.0001). ALDH1 + cells were associated with mild dysplasia using a system from the World Health Organization (WHO), and with a low risk of malignant transformation, according to the binary system (p<0.0001). CD44+ cells were also associated with moderated dysplasia, according to the WHO system. In LSCC, ALDH1 + cells were positively associated with patients who were older (≥ 60 years old), smokers, and with those who consumed alcohol (p<0.0001). CD44 + cells in LSCC were associated with older (≥ 60 years old) patients as well, but also with female patients, white skin, non-smokers, and individuals who did not consume alcohol (p<0.0001), all of whom showed distinct patterns in pre- and malignant lesions of both markers. Additionally, in LSCC, both ALDH1 and CD44 staining were associated with smaller tumor sizes (T1/T2; p<0.0001). In summary, although both ALDH1 and CD44 were associated with the presence of dysplasia in AC lesions, the present findings suggest that ALDH1 and CD44 may be activated by different etiopathogenic pathways, predominantly in distinct steps of oral carcinogenesis. CD44 would thus be more significantly related to the potentially malignant lesion, while ALDH1 would be closely linked to malignancy.


Assuntos
Neoplasias Labiais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Família Aldeído Desidrogenase 1 , Biomarcadores Tumorais , Carcinogênese , Receptores de Hialuronatos/metabolismo , Lábio/metabolismo , Lábio/patologia , Neoplasias Labiais/etiologia , Neoplasias Labiais/metabolismo , Neoplasias Labiais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/etiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
13.
J Bone Miner Res ; 38(8): 1135-1153, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37314430

RESUMO

Leukotrienes (LTs) are derived from arachidonic acid metabolism by the 5-lipoxygenase (5-LO) enzyme. The production of LTs is stimulated in the pathogenesis of rheumatoid arthritis (RA), osteoarthritis, and periodontitis, with a relevant contribution to bone resorption. However, its role in bone turnover, particularly the suppression of bone formation by modulating the function of osteoclasts and osteoblasts, remains unclear. We investigated the effects of LTs on bone metabolism and their impact on osteogenic differentiation and osteoclastogenesis using a 5-LO knockout (KO) mouse model. Results from micro-computed tomography (µCT) analysis of femur from 8-week-old 5-LO-deficient mice showed increased cortical bone and medullary region in females and males and decreased trabecular bone in females. In the vertebra, we observed increased marrow area in both females and males 5-LO KO and decreased trabecular bone only in females 5-LO KO. Immunohistochemistry (IHC) analysis showed higher levels of osteogenic markers tissue-nonspecific alkaline phosphatase (TNAP) and osteopontin (OPN) and lower expression of osteoclastogenic marker tartrate-resistant acid phosphatase (TRAP) in the femurs of 5-LO KO mice versus wild-type (WT). Alkaline phosphatase activity and mineralization assay results showed that the 5-LO absence enhances osteoblasts differentiation and mineralization but decreases the proliferation. Alkaline phosphatase (ALP), Bglap, and Sp7 gene expression were higher in 5-LO KO osteoblasts compared to WT cells. Eicosanoids production was higher in 5-LO KO osteoblasts except for thromboxane 2, which was lower in 5-LO-deficient mice. Proteomic analysis identified the downregulation of proteins related to adenosine triphosphate (ATP) metabolism in 5-LO KO osteoblasts, and the upregulation of transcription factors such as the adaptor-related protein complex 1 (AP-1 complex) in long bones from 5-LO KO mice leading to an increased bone formation pattern in 5-LO-deficient mice. We observed enormous differences in the morphology and function of osteoclasts with reduced bone resorption markers and impaired osteoclasts in 5-LO KO compared to WT osteoclasts. Altogether, these results demonstrate that the absence of 5-LO is related to the greater osteogenic profile. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).


Assuntos
Reabsorção Óssea , Osteogênese , Masculino , Feminino , Camundongos , Animais , Fosfatase Alcalina/metabolismo , Microtomografia por Raio-X , Proteômica , Osteoclastos/metabolismo , Osteoblastos/metabolismo , Reabsorção Óssea/patologia , Diferenciação Celular , Camundongos Knockout , Leucotrienos/metabolismo , Leucotrienos/farmacologia
14.
Dermatology ; 239(5): 685-693, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37257423

RESUMO

BACKGROUND: Vismodegib is approved for advanced cases of basal cell carcinomas not amenable to surgery or radiotherapy. Large studies on the use of vismodegib in clinical practice are scarce. OBJECTIVES: The main objective of the study was to analyse the evolution and therapeutic management of relapses and lack of response in patients who had received vismodegib for locally advanced and/or multiple basal cell carcinomas in a real-life multicentre setting. METHODS: This nationwide retrospective study collected data on patients treated with vismodegib in 15 specialized centres. We included patients who first received vismodegib until intolerable toxicity, maximum response, or progressive disease. Exploratory research variables referred to patient and tumour characteristics, vismodegib effectiveness and safety, relapse rate and management, and mortality. A multivariable logistic regression model was used to identify predictors of complete clinical response. RESULTS: 133 patients with advanced BCC were included in the registry. The objective response rate (ORR) was 77.5% and nearly half of the patients (45.9%) achieved complete remission. Long-term information and detailed information of subsequent treatments after a regime of vismodegib was available for 115 patients. Only 34% of the patients in this group were subsequently treated with other therapies or vismodegib rechallenge. Sixty-nine percent of the patients who had shown a complete remission with vismodegib remained free of recurrence while 30.7% relapsed. Almost half of the patients who received additional therapies after the first course of vismodegib achieved complete tumour remission. Three and 2 out of 9 patients who were rechallenged with vismodegib achieved complete and partial responses, respectively, with an ORR of 55.5%. CONCLUSION: Our study confirms efficacy of vismodegib in routine clinical practice. The risk of recurrence after achieving complete response with vismodegib was lower than previous reports. Rechallenge with vismodegib is feasible and most patients responded to re-treatment.


Assuntos
Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/patologia , Estudos Retrospectivos , Antineoplásicos/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Carcinoma Basocelular/patologia , Anilidas/uso terapêutico
15.
Mol Cell Proteomics ; 22(6): 100547, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37059366

RESUMO

Basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (SCCs) are the most frequent types of cancer, and both originate from the keratinocyte transformation, giving rise to the group of tumors called keratinocyte carcinomas (KCs). The invasive behavior is different in each group of KC and may be influenced by their tumor microenvironment. The principal aim of the study is to characterize the protein profile of the tumor interstitial fluid (TIF) of KC to evaluate changes in the microenvironment that could be associated with their different invasive and metastatic capabilities. We obtained TIF from 27 skin biopsies and conducted a label-free quantitative proteomic analysis comparing seven BCCs, 16 SCCs, and four normal skins. A total of 2945 proteins were identified, 511 of them quantified in more than half of the samples of each tumoral type. The proteomic analysis revealed differentially expressed TIF proteins that could explain the different metastatic behavior in both KCs. In detail, the SCC samples disclosed an enrichment of proteins related to cytoskeleton, such as Stratafin and Ladinin-1. Previous studies found their upregulation positively correlated with tumor progression. Furthermore, the TIF of SCC samples was enriched with the cytokines S100A8/S100A9. These cytokines influence the metastatic output in other tumors through the activation of NF-kB signaling. According to this, we observed a significant increase in nuclear NF-kB subunit p65 in SCCs but not in BCCs. In addition, the TIF of both tumors was enriched with proteins involved in the immune response, highlighting the relevance of this process in the composition of the tumor environment. Thus, the comparison of the TIF composition of both KCs provides the discovery of a new set of differential biomarkers. Among them, secreted cytokines such as S100A9 may help explain the higher aggressiveness of SCCs, while Cornulin is a specific biomarker for BCCs. Finally, the proteomic landscape of TIF provides key information on tumor growth and metastasis, which can contribute to the identification of clinically applicable biomarkers that may be used in the diagnosis of KC, as well as therapeutic targets.


Assuntos
Carcinoma Basocelular , Carcinoma de Células Escamosas , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/metabolismo , Líquido Extracelular/metabolismo , NF-kappa B/metabolismo , Proteômica , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/metabolismo , Queratinócitos/metabolismo , Biomarcadores Tumorais/metabolismo , Microambiente Tumoral
16.
J Am Acad Dermatol ; 89(1): 119-127, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36907554

RESUMO

BACKGROUND: Satellitosis or in-transit metastasis (S-ITM) has clinical outcomes comparable to node-positivity in cutaneous squamous cell carcinoma (cSCC). There is a need to stratify the risk groups. OBJECTIVE: To determine which prognostic factors of S-ITM confer an increased risk of relapse and cSCC-specific-death. METHODS: A retrospective, multicenter cohort study. Patients with cSCC developing S-ITM were included. Multivariate competing risk analysis evaluated which factors were associated with relapse and specific death. RESULTS: Of a total of 111 patients with cSCC and S-ITM, 86 patients were included for analysis. An S-ITM size of ≥20 mm, >5 S-ITM lesions, and a primary tumor deep invasion was associated with an increased cumulative incidence of relapse (subhazard ratio [SHR]: 2.89 [95% CI, 1.44-5.83; P = .003], 2.32 [95% CI, 1.13-4.77; P = .021], and 2.863 [95% CI, 1.25-6.55; P = .013]), respectively. Several >5 S-ITM lesions were also associated with an increased probability of specific death (SHR: 3.48 [95% CI, 1.18-10.2; P = .023]). LIMITATIONS: Retrospective study and heterogeneity of treatments. CONCLUSION: The size and the number of S-ITM lesions confer an increased risk of relapse and the number of S-ITM an increased risk of specific-death in patients with cSCC presenting with S-ITM. These results provide new prognostic information and can be considered in the staging guidelines.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Humanos , Carcinoma de Células Escamosas/patologia , Estudos de Coortes , Estudos Retrospectivos , Prognóstico , Neoplasias Cutâneas/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Fatores de Risco , Recidiva , Estadiamento de Neoplasias
17.
Interv Neuroradiol ; 29(6): 683-690, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35673710

RESUMO

BACKGROUND: Middle meningeal artery (MMA) embolization is an apparently efficacious minimally invasive treatment for nonacute subdural hematomas (NASHs), but how different embolisates affect outcomes remains unclear. Our objective was to compare radiographic and clinical outcomes after particle or liquid MMA embolization. METHODS: Patients who had MMA embolization for NASH were retrospectively identified from a multi-institution database. The primary radiographic and clinical outcomes-50% NASH thickness reduction and need for surgical retreatment within 90 days, respectively-were compared for liquid and particle embolizations in patients treated 1) without surgical intervention (upfront), 2) after recurrence, or 3) with concomitant surgery (prophylactic). RESULTS: The upfront, recurrent, and prophylactic subgroups included 133, 59, and 16 patients, respectively. The primary radiographic outcome was observed in 61.8%, 61%, and 72.7% of particle-embolized patients and 61.3%, 55.6%, and 20% of liquid-embolized patients, respectively (p = 0.457, 0.819, 0.755). Hazard ratios comparing time to reach radiographic outcome in the particle and liquid groups or upfront, recurrent, andprophylactic timing were 1.31 (95% CI 0.78-2.18; p = 0.310), 1.09 (95% CI 0.52-2.27; p = 0.822), and 1.5 (95% CI 0.14-16.54; p = 0.74), respectively. The primary clinical outcome occurred in 8.0%, 2.4%, and 0% of patients who underwent particle embolization in the upfront, recurrent, and prophylactic groups, respectively, compared with 0%, 5.6%, and 0% who underwent liquid embolization (p = 0.197, 0.521, 1.00). CONCLUSIONS: MMA embolization with particle and liquid embolisates appears to be equally effective in treatment of NASHs as determined by the percentage who reach, and the time to reach, 50% NASH thickness reduction and the incidence of surgical reintervention within 90 days.


Assuntos
Embolização Terapêutica , Hematoma Subdural Crônico , Hepatopatia Gordurosa não Alcoólica , Humanos , Hematoma Subdural Crônico/terapia , Artérias Meníngeas/diagnóstico por imagem , Estudos Retrospectivos , Hepatopatia Gordurosa não Alcoólica/terapia , Resultado do Tratamento , Embolização Terapêutica/métodos
18.
Hand (N Y) ; 18(4): 655-661, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-34872360

RESUMO

BACKGROUND: We attempted to evaluate patient satisfaction and overall experience during wide awake, local anesthesia, with no tourniquet (WALANT) hand surgery and quantify surgery-related outcomes. METHODS: We conducted a retrospective analysis of patient demographics, comorbidities, and patient reported outcomes via Single Assessment Numeric Evaluation (SANE) scores collected pre- and postoperatively of patients undergoing WALANT surgery by the 2 participating senior authors. A solution of 1% lidocaine with 1:100,000 epinephrine was used by 1 surgeon, while the other used a 1:1 ratio of 1% lidocaine with 1:100,000 epinephrine and 0.5% bupivacaine for local anesthetic injection. Patients were administered a postoperative survey to assess patient experience, including anxiety and pain levels, and overall satisfaction in the perioperative period. RESULTS: Overall, 97.7% of patients indicated that they would undergo a WALANT-style surgery if indicated in the future, 70.5% ate the day of surgery, and a total of 39.1% of patients reported driving to and from surgery. Postoperative SANE scores increased as compared with preoperative scores across all patients. The use of combination 1% lidocaine with 1:100,000 epinephrine and 0.5% bupivacaine was associated with lower intraoperative and postoperative visual analog scale pain scores. CONCLUSIONS: WALANT hand surgery was generally well tolerated with excellent surgical outcomes. Patients reported ease of preparation for surgery, faster recovery, and lack of anesthetic side effects as the main benefits of wide-awake surgery. Combination use of lidocaine and bupivacaine may be better than lidocaine alone with respect to pain control in the initial recovery period.


Assuntos
Anestesia Local , Neoplasias Encefálicas , Humanos , Anestesia Local/métodos , Mãos/cirurgia , Estudos Retrospectivos , Vigília , Lidocaína , Epinefrina , Bupivacaína , Avaliação de Resultados da Assistência ao Paciente , Dor
19.
J. appl. oral sci ; 31: e20230227, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1528881

RESUMO

Abstract Lip squamous cell carcinoma (LSCC) accounts for 12% of all head and neck cancers. It is caused by chronic exposure to ultraviolet light solar radiation and related to previous actinic cheilitis (AC). This study aimed to investigate the immunostaining of the putative cancer stem cells (CSC) markers ALDH1 and CD44 in AC (n=30) and LSCC (n=20). ALDH1 positivity was found to be statistically higher in LSCC than in AC lesions (p=0.0045), whilst CD44 expression was statistically higher in AC than in LSCC lesions (p=0.0155). ALDH1+ cells in AC lesions were associated with specific clinical features: a younger age (<60 years old), the female gender, white skin, not smoking or consuming alcohol, and a fast evolution, and not associated with the chronic exposure to UV radiation (p<0.0001). CD44 positivity was associated with patients who were male, feoderm, smoked, consumed alcohol, underwent occupational exposure to UV-radiation, and demonstrated lesions with log-time evolution (p<0.0001). ALDH1 + cells were associated with mild dysplasia using a system from the World Health Organization (WHO), and with a low risk of malignant transformation, according to the binary system (p<0.0001). CD44+ cells were also associated with moderated dysplasia, according to the WHO system. In LSCC, ALDH1 + cells were positively associated with patients who were older (≥ 60 years old), smokers, and with those who consumed alcohol (p<0.0001). CD44 + cells in LSCC were associated with older (≥ 60 years old) patients as well, but also with female patients, white skin, non-smokers, and individuals who did not consume alcohol (p<0.0001), all of whom showed distinct patterns in pre- and malignant lesions of both markers. Additionally, in LSCC, both ALDH1 and CD44 staining were associated with smaller tumor sizes (T1/T2; p<0.0001). In summary, although both ALDH1 and CD44 were associated with the presence of dysplasia in AC lesions, the present findings suggest that ALDH1 and CD44 may be activated by different etiopathogenic pathways, predominantly in distinct steps of oral carcinogenesis. CD44 would thus be more significantly related to the potentially malignant lesion, while ALDH1 would be closely linked to malignancy.

20.
Rev. bras. ortop ; 57(6): 1065-1069, Nov.-Dec. 2022. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1423643

RESUMO

Abstract Objective To demonstrate the degree of recommendation of mentors and mentees regarding a mentorship program, to assess the degree of satisfaction of the participants, and to describes the main characteristics of the meetings in pairs. Materials and Methods A primary, retrospective, analytical study based on answers to the annual evaluation questionnaires of the institutional mentorship program in pairs of the Orthopedics and Traumatology residency from December 2017 to February 2021. Results We compiled 52 responses from 26 mentorship preceptors and 26 mentored residents. The mentees and mentors had average ages of 27 (±1.5) years and 45 (±8.2) years respectively. A total of 96% of the participants recommend the program, and 89% of the mentees reported that the mentors contributed to their personal and professional decision-making process. Conclusion The mentorship program proved to be a highly recommended strategy in medical residency in Orthopedics. Data show that mentors contributed to the mentees' personal and professional decision-making process.


Resumo Objetivo Demonstrar o grau de recomendação de mentores e mentorados quanto à participação em um programa de mentoria, avaliar o grau de satisfação dos participantes, e descrever as principais características das reuniões em dupla. Materiais e Métodos Estudo primário, retrospectivo, analítico, com análise das respostas dos questionários de avaliação anual do programa de mentoria em dupla da residência de Ortopedia e Traumatologia da instituição de dezembro de 2017 a fevereiro de 2021. Resultados Foram obtidas 52 respostas de 26 preceptores mentores e 26 residentes mentorados. A média de idade dos mentorados foi de 27 anos (±1,5 ano), ao passo que a média de idade dos mentores foi de 45 anos (±8,2 anos). O grau de recomendação do programa pelos participantes foi de 96%, e 89% dos mentorados consideraram que os mentores contribuíram para a tomada de decisões pessoais e profissionais. Conclusão O programa de mentoria se mostrou uma estratégia com alto grau de recomendação na residência médica em Ortopedia. Os dados mostram que os mentores contribuíram para a tomada de decisões pessoais e profissionais dos mentorados.


Assuntos
Humanos , Adulto , Ortopedia/educação , Traumatologia/educação , Mentores , Internato e Residência
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