Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 912
Filtrar
Mais filtros


Intervalo de ano de publicação
1.
BMC Infect Dis ; 21(1): 1155, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34774006

RESUMO

BACKGROUND: Individuals with relapses of leprosy should be monitored carefully, however, with respect to paucibacillary (PB) leprosy, it is sometimes difficult to make a definitive diagnosis of relapse, because the bacillary index is often negative. To evaluate the usefulness of cytokine profiling in a patient with relapsed PB leprosy who tested negative for anti-phenolic glycolipid-I antibodies, we analyzed the Mycobacterium leprae protein-induced cytokine expression in peripheral blood mononuclear cells of the patient. CASE PRESENTATION: An 89-year-old-male relapsed PB patient, first treated for leprosy over 50 years prior, was examined. In April 2012, he noticed three skin lesions consisting of annular erythema in the thighs. Slit skin smear tests were negative, and skin biopsies revealed a pathology of indeterminate-to-borderline tuberculoid leprosy. He received 600 mg of rifampicin once per month and 75 mg of dapsone daily for 12 months. The annular erythemas disappeared after starting treatment. Before treatment, and 6 and 12 months after starting treatment, the Th1/Th2 cytokine profiles in the supernatant of mononuclear cells from the patient before and after stimulation with Mycobacterium leprae soluble protein (MLS) were examined using a Cytometric Bead Array (CBA) Human Th1/Th2 Cytokine Kit II. The CBA Enhanced Sensitivity Flex Set system was applied to detect small amounts of cytokines in the serum just before treatment and one year before relapse. In the culture supernatant, just before treatment, increases in IFN-γ level and the IFN-γ/IL-10 ratio and a decreased IL-6 level were observed without stimulation. Upon stimulation with MLS, just before treatment, both the IFN-γ and TNF levels increased markedly, and twelve months after starting treatment, the IFN-γ and TNF levels decreased greatly. In the serum, just before treatment, increases in IFN-γ and TNF levels and the IFN-γ/IL-10 ratio were evident compared with those measured one year before relapse. CONCLUSIONS: Cytokine profiling using culture supernatants and serum samples may be useful for the diagnosis of relapsed PB leprosy.


Assuntos
Hanseníase Paucibacilar , Hanseníase , Idoso de 80 Anos ou mais , Citocinas , Humanos , Hanseníase Paucibacilar/diagnóstico , Hanseníase Paucibacilar/tratamento farmacológico , Leucócitos Mononucleares , Masculino , Mycobacterium leprae
2.
Cells ; 10(9)2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34571865

RESUMO

Leprosy reactional episodes are acute inflammatory events that may occur during the clinical course of the disease. Type 1 reaction (T1R) is associated with an increase in neural damage, and the understanding of the molecular pathways related to T1R onset is pivotal for the development of strategies that may effectively control the reaction. Interferon-gamma (IFN-γ) is a key cytokine associated with T1R onset and is also associated with autophagy induction. Here, we evaluated the modulation of the autophagy pathway in Mycobacterium leprae-stimulated cells in the presence or absence of IFN-γ. We observed that IFN-γ treatment promoted autophagy activation and increased the expression of genes related to the formation of phagosomes, autophagy regulation and function, or lysosomal pathways in M. leprae-stimulated cells. IFN-γ increased interleukin (IL)-15 secretion in M. leprae-stimulated THP-1 cells in a process associated with autophagy activation. We also observed higher IL15 gene expression in multibacillary (MB) patients who later developed T1R during clinical follow-up when compared to MB patients who did not develop the episode. By overlapping gene expression patterns, we observed 13 common elements shared between T1R skin lesion cells and THP-1 cells stimulated with both M. leprae and IFN-γ. Among these genes, the autophagy regulator Translocated Promoter Region, Nuclear Basket Protein (TPR) was significantly increased in T1R cells when compared with non-reactional MB cells. Overall, our results indicate that IFN-γ may induce a TPR-mediated autophagy transcriptional program in M. leprae-stimulated cells similar to that observed in skin cells during T1R by a pathway that involves IL-15 production, suggesting the involvement of this cytokine in the pathogenesis of T1R.


Assuntos
Autofagia/genética , Interleucina-15/genética , Hanseníase/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Cultivadas , Criança , Citocinas/genética , Feminino , Expressão Gênica/genética , Humanos , Interferon gama/genética , Hanseníase/microbiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/patogenicidade , Pele/metabolismo , Pele/microbiologia , Células THP-1/metabolismo , Adulto Jovem
3.
Front Immunol ; 12: 662307, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354699

RESUMO

The treatment of multibacillary cases of leprosy with multidrug therapy (MDT) comprises 12 doses of a combination of rifampicin, dapsone and clofazimine. Previous studies have described the immunological phenotypic pattern in skin lesions in multibacillary patients. Here, we evaluated the effect of MDT on skin cell phenotype and on the Mycobacterium leprae-specific immune response. An analysis of skin cell phenotype demonstrated a significant decrease in MRS1 (SR-A), CXCL10 (IP-10) and IFNG (IFN-γ) gene and protein expression after MDT release. Patients were randomized according to whether they experienced a reduction in bacillary load after MDT. A reduction in CXCL10 (IP-10) in sera was associated with the absence of a reduction in the bacillary load at release. Although IFN-γ production in response to M. leprae was not affected by MDT, CXCL10 (IP-10) levels in response to M. leprae increased in cells from patients who experienced a reduction in bacillary load after treatment. Together, our results suggest that CXCL10 (IP-10) may be a good marker for monitoring treatment efficacy in multibacillary patients.


Assuntos
Quimiocina CXCL10/sangue , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Pele/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carga Bacteriana/efeitos dos fármacos , Biomarcadores/sangue , Quimiocina CXCL10/imunologia , Quimioterapia Combinada , Feminino , Humanos , Hansenostáticos/administração & dosagem , Hanseníase/imunologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/imunologia , Pele/microbiologia , Pele/patologia , Resultado do Tratamento , Adulto Jovem
4.
Am J Trop Med Hyg ; 105(1): 31-36, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34232909

RESUMO

Leprosy is an infectious disease caused by Mycobacterium leprae. China was once one of the countries with severe leprosy epidemics, but its incidence has remained low in recent years. Despite this, there has been no decrease in its incidence more recently, and it is still a public health problem which needs to be controlled. In this study, we analyzed the epidemiological characteristics and trends in the detection rate of new cases of leprosy in China between 2004 and 2016. There were 4,519 cases of leprosy in 28 provinces, municipalities, and autonomous regions between 2004 and 2016, and the total incidence was 0.02815 (per 100,000 individuals) and 21 deaths. The overall incidence of leprosy showed an inverted "V" distribution (i.e., an increase followed by a decrease). Yunnan, Sichuan, Guangdong, Guizhou, and Guangxi were the top five regions with the highest incidence rates, and they accounted for 68.7% of the total cases. There were more male patients than female patients, and peasants accounted for 71.7% of the leprosy cases. The patients with leprosy in China were mainly concentrated in the age-group 15-44 years, as this group accounted for 57.2% of the total cases. The purpose of this study is to explore the epidemiology of leprosy in China. This analysis will be useful for future monitoring of leprosy and establishment of public health measures in China, in keeping with the "Programme for the Elimination of Leprosy in China 2011-2020."


Assuntos
Hanseníase/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/isolamento & purificação , Estudos Retrospectivos , Adulto Jovem
5.
PLoS Negl Trop Dis ; 15(6): e0009495, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34125854

RESUMO

BACKGROUND: This study evaluates implementation strategies for leprosy diagnosis based on responses to a Leprosy Suspicion Questionnaire (LSQ), and analyzes immunoepidemiological aspects and follow-up of individuals living in a presumptively nonendemic area in Brazil. METHODOLOGY/PRINCIPAL FINDINGS: Quasi-experimental study based on LSQ throughout Jardinópolis town by community health agents, theoretical-practical trainings for primary care teams, dermatoneurological examination, anti-PGL-I serology, RLEP-PCR, and spatial epidemiology. A Leprosy Group (LG, n = 64) and Non-Leprosy Group (NLG, n = 415) were established. Overall, 3,241 LSQs were distributed; 1,054 (32.5%) LSQ were positive for signs/symptoms (LSQ+). Among LSQ+ respondents, Q2-Tingling (pricking)? (11.8%); Q4-Spots on the skin? (11.7%); Q7-Pain in the nerves? (11.6%); Q1-Numbness in your hands and/or feet? (10.7%) and Q8-Swelling of hands and feet? (8.5%) were most frequently reported symptoms. We evaluated 479 (14.8%) individuals and diagnosed 64 new cases, a general new case detection rate (NCDR) of 13.4%; 60 were among 300 LSQ+ (NCDR-20%), while 4 were among 179 LSQ negative (NCDR-2.23%). In LG, Q7(65%), Q2(60%), Q1(45%), Q4(40%) and Q8(25%) were most frequent. All 2x2 crossings of these 5 questions showed a relative risk for leprosy ranging from 3 to 5.8 compared with NLG. All patients were multibacillary and presented hypochromatic macules with loss of sensation. LG anti-PGL-I titers were higher than NLG, while 8.9% were positive for RLEP-PCR. The leprosy cases and anti-PGL-I spatial mappings demonstrated the disease spread across the town. CONCLUSIONS/SIGNIFICANCE: Implementation actions, primarily LSQ administration focused on neurological symptoms, indicate hidden endemic leprosy in a nonendemic Brazilian state.


Assuntos
Agentes Comunitários de Saúde/educação , Hanseníase/diagnóstico , Hanseníase/epidemiologia , Mycobacterium leprae/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/genética , Mycobacterium leprae/isolamento & purificação , Prevalência , Inquéritos e Questionários
6.
PLoS One ; 16(5): e0251631, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33984058

RESUMO

The number of new cases of leprosy reported worldwide has remained essentially unchanged for the last decade despite continued global use of free multidrug therapy (MDT) provided to any diagnosed leprosy patient. In order to more effectively interrupt the chain of transmission, new strategies will be required to detect those with latent disease who contribute to furthering transmission. To improve the ability to diagnose leprosy earlier in asymptomatic infected individuals, we examined the combined use of two well-known biomarkers of M. leprae infection, namely the presence of M. leprae DNA by PCR from earlobe slit skin smears (SSS) and positive antibody titers to the M. leprae-specific antigen, Phenolic Glycolipid I (anti-PGL-I) from leprosy patients and household contacts living in seven hyperendemic cities in the northern state of Pará, Brazilian Amazon. Combining both tests increased sensitivity, specificity and accuracy over either test alone. A total of 466 individuals were evaluated, including 87 newly diagnosed leprosy patients, 52 post-treated patients, 296 household contacts and 31 healthy endemic controls. The highest frequency of double positives (PGL-I+/RLEP+) were detected in the new case group (40/87, 46%) with lower numbers for treated (12/52, 23.1%), household contacts (46/296, 15.5%) and healthy endemic controls (0/31, 0%). The frequencies in these groups were reversed for double negatives (PGL-I-/RLEP-) for new cases (6/87, 6.9%), treated leprosy cases (15/52, 28.8%) and the highest in household contacts (108/296, 36.5%) and healthy endemic controls (24/31, 77.4%). The data strongly suggest that household contacts that are double positive have latent disease, are likely contributing to shedding and transmission of disease to their close contacts and are at the highest risk of progressing to clinical disease. Proposed strategies to reduce leprosy transmission in highly endemic areas may include chemoprophylactic treatment of this group of individuals to stop the spread of bacilli to eventually lower new case detection rates in these areas.


Assuntos
Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Glicolipídeos/imunologia , Infecção Latente/diagnóstico , Hanseníase/diagnóstico , Mycobacterium leprae/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , DNA Bacteriano/análise , Feminino , Humanos , Infecção Latente/imunologia , Hanseníase/imunologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/imunologia , Adulto Jovem
7.
PLoS Negl Trop Dis ; 15(5): e0009382, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33939710

RESUMO

The World Health Organization has raised concerns about the increasing number of Hansen disease (HD) relapses worldwide, especially in Brazil, India, and Indonesia that report the highest number of recurrent cases. Relapses are an indicator of MDT effectiveness and can reflect Mycobacterium leprae persistence or re-infection. Relapse is also a potential marker for the development or progression of disability. In this research, we studied a large cohort of persons affected by HD treated with full fixed-dose multibacillary (MB) multidrug therapy (MDT) followed for up to 20 years and observed that relapses are a rare event. We estimated the incidence density of relapse in a cohort of patients classified to receive MB regime (bacillary index (BI) > 0), diagnosed between September 1997 and June 2017, and treated with twelve-dose MB-MDT at a HD reference center in Rio de Janeiro, Brazil. We obtained the data from the data management system of the clinic routine service. We linked the selected cases to the dataset of relapses of the national HD data to confirm possible relapse cases diagnosed elsewhere. We diagnosed ten cases of relapse in a cohort of 713 patients followed-up for a mean of 12.1 years. This resulted in an incidence rate of 1.16 relapse cases per 1000 person-year (95% CI = 0.5915-2.076). The accumulated risk was 0.025 in 20 years. The very low risk observed in this cohort of twelve-dose-treated MB patients reinforces the success of the current MDT scheme.


Assuntos
Hansenostáticos/uso terapêutico , Hanseníase Virchowiana/tratamento farmacológico , Hanseníase Virchowiana/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Criança , Pré-Escolar , Clofazimina/uso terapêutico , Dapsona/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/efeitos dos fármacos , Recidiva , Estudos Retrospectivos , Rifampina/uso terapêutico , Pele/microbiologia , Pele/patologia , Adulto Jovem
8.
Mycoses ; 64(11): 1442-1447, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33966290

RESUMO

BACKGROUND: Recurrent and clinically unresponsive dermatophytosis is being increasingly observed in India. However, there is little information regarding the extent of the problem and the factors responsible for these difficult to treat superficial fungal infections. AIM: To identify factors contributing to difficult to treat recurrent superficial fungal infections. MATERIALS AND METHODS: This prospective cross-sectional study enrolled 105 patients of all age groups presenting with either recurrent or long-standing dermatophyte infection attending the outpatient department of Dermatology, Venerology and Leprosy of Bharati Hospital, Pune, India, between September 2018 and March 2020. Patients were clinically examined, clinical history was taken and questions were asked regarding their current complaints and recorded in a proforma. Data were analysed using the SPSS software package. RESULTS: The males outnumbered females (74.3% vs 25.7%). A strong association was observed between the presence of past history and duration of disease (p = .007). The association of use of topical steroids or keratolytic agents with the duration of disease was statistically significant (p = .022). There was a statistically significant inverse association of duration of disease with dermatologist consultation (p < .001). The association between consultation with non-dermatologist and the duration of disease was statistically significant (p = .035). CONCLUSION: Hyperhidrosis, obesity, positive family history, tight clothing and chronic diseases may be considered important factors in acquiring dermatophytic infection. However, when it comes to difficult to treat tinea infections, irrational usage of topical steroids, treatment from non-dermatologists and a past history of tinea appear to be more critical causative factors. Treatment of dermatophytosis by dermatologists/ trained physicians and increasing general awareness of the public regarding the current situation about tinea in the country would help to alleviate the current crisis.


Assuntos
Dermatomicoses/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Índia/epidemiologia , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Centros de Atenção Terciária , Adulto Jovem
9.
J Pak Med Assoc ; 71(3): 838-842, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34057932

RESUMO

OBJECTIVE: To determine the occurrence and characteristics of the two types of lepra reactions in new leprosy cases at initial diagnosis. Methods: The retrospective descriptive study was conducted at the Marie Adelaide Leprosy Centre, Karachi, and comprised all new leprosy cases registered from January 1, 2016, to June 30, 2018. Data was collected from the medical record database using a predesigned proforma. RESULTS: Of the 50 cases, 2(4%) were children and 48 (96%) were adults, with overall age ranging from 12 to 85 years. There were 41(82%) males and 9(18%) females.. Of the total, 30(60%) cases presented with type 1 reaction and 20(40%) with type 2. Further, 30(60%) cases were classified as borderline lepromatous. Among them, 17(57%) had type 2 reaction. Inflamed plaques were the main feature in 27(90%) cases of type 1. Crops of painful, erythematous nodules were seen in 19(95%) cases of type 2. Conclusion: Lepra reactions were found to be a presenting feature in a significant number of new leprosy cases at initial diagnosis.


Assuntos
Hanseníase , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Hanseníase/diagnóstico , Hanseníase/epidemiologia , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Estudos Retrospectivos , Adulto Jovem
10.
Indian J Dermatol Venereol Leprol ; 87(3): 348-356, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33666033

RESUMO

BACKGROUND: There are few studies on basal cell carcinoma (BCC) from India. Long-term follow-up is available in only one study and the aesthetic outcome of treatment has not been evaluated in Indian patients. AIMS: In this retrospective study on BCC, we compared treatment failure, recurrence rates and aesthetic outcomes on long-term follow-up between surgical excision and repair, and nonsurgical and ablative treatments. METHODS: Records of patients with BCC treated in the dermatologic surgery clinic over the past 10 years were analyzed. Patients with histopathologically confirmed BCC who could be contacted were evaluated for recurrence, treatment failure, overall satisfaction and aesthetic outcomes by global aesthetic improvement scale. RESULTS: Out of 98 patients, 72 were contactable. Four patients received both nonsurgical and ablative treatments and surgical excision and repair sequentially and were excluded. The mean age of patients was 57.9 ± 15.8 years (24-90 years) and the male: female ratio was 1.6:1. The most common site involved was the face (72.1%) followed by trunk and scalp, and the most common type of BCC was the pigmented superficial type (33.8%), followed by the pigmented noduloulcerative type (16.2%). There was no significant difference between the groups in the number of high-risk cases. The mean follow-up period was 37.1 ± 31.4 (range, 4-120) months. Fifty one patients were treated with surgical excision and repair, and 17 with nonsurgical and ablative treatments (9-imiquimod, 5-cryotherapy, 4-radiotherapy). Treatment failure was seen in 5 (7.4%) patients, all in the nonsurgical and ablative treatments group (P = 0.0006). Recurrence was seen in 2 (2.9%) patients, both in the surgical excision and repair group (P > 0.05). Mean patient satisfaction was significantly higher with surgical excision and repair, though there was no significant difference in the Global Aesthetic Improvement Scale between the groups. LIMITATIONS: The sample size was low. Only telephonic and pictorial assessments were done where the patient could not come for follow-up. CONCLUSIONS: Surgical excision and repair was associated with better outcomes than nonsurgical and ablative treatments. Treatment failures and adverse events were high with nonsurgical and ablative treatments. The recurrence rate was low.


Assuntos
Carcinoma Basocelular/terapia , Neoplasias Cutâneas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Crioterapia , Feminino , Humanos , Imiquimode/uso terapêutico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Satisfação do Paciente , Ablação por Radiofrequência , Estudos Retrospectivos , Adulto Jovem
11.
PLoS Negl Trop Dis ; 15(3): e0009201, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33725010

RESUMO

BACKGROUND: This study reviews the progress of leprosy elimination in Yunnan, China, over the past 30 years and identifies the challenges for the next stage of the program. METHODOLOGY/PRINCIPAL FINDINGS: Data were collected from the Leprosy Management Information System in China (LEPMIS). The progress made in the elimination of leprosy between 1990 and 2019 was measured. We defined two time periods, time period 1 (1990-2003) and time period 2 (2004-2019), because multidrug therapy (MDT) was launched for the treatment of leprosy in 1990 and a special fund from the central government was established for leprosy in 2004. During the past 30 years, the number of newly detected leprosy patients in Yunnan has steadily declined. In total, 703 newly detected leprosy patients were reported in 1990, and 353 and 136 cases were reported at the end of 2003 and 2019, respectively. At the end of 1990, 90.7% (117/129) of counties in Yunnan Province were identified as leprosy-endemic counties (>1 case per 100,000 population). By the end of 2003 and 2019, 39.3% (46/117) and 85.5% (100/117) of the leprosy-endemic counties, respectively, had dropped below the elimination threshold. The main challenges are the remaining leprosy-endemic counties, the high rate of cases with a contact history, insufficient early detection, and leprosy cases resulting in physical disability. CONCLUSIONS/SIGNIFICANCE: A multifaceted strategy for leprosy elimination in Yunnan Province has been successfully implemented, and remarkable progress has been made in the elimination of leprosy in this area. The priorities for leprosy elimination in the next stage are securing sustainable support and investment from the government, establishing an effective surveillance system, ensuring prompt early detection, providing treatment with MDT, preventing transmission of M. leprae, preventing disability, providing health education, and preventing recurrence of the epidemic situation of leprosy.


Assuntos
Erradicação de Doenças , Hanseníase/epidemiologia , Hanseníase/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Vigilância da População , Fatores de Tempo , Adulto Jovem
12.
PLoS Negl Trop Dis ; 15(3): e0009214, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33690671

RESUMO

BACKGROUND: Leprosy continues to be a public health problem in Brazil. Furthermore, detection rates in elderly people have increased, particularly those of multibacillary (L-Lep) patients, who are responsible for transmitting M. leprae. Part of the decline in physiological function during aging is due to increased oxidative damage and change in T cell subpopulations, which are critical in defense against the disease. It is not still clear how age-related changes like those related to oxidation affect elderly people with leprosy. The aim of this work was to verify whether the elderly leprosy patients have higher ROS production and how it can impact the evolution of leprosy. METHODOLOGY/PRINCIPAL FINDINGS: 87 leprosy patients, grouped according to age range and clinical form of leprosy, and 25 healthy volunteers were analyzed. Gene expression analysis of antioxidant and oxidative burst enzymes were performed in whole blood using Biomark's microfluidic-based qPCR. The same genes were evaluated in skin lesion samples by RT-qPCR. The presence of oxidative damage markers (carbonylated proteins and 4-hydroxynonenal) was analyzed by a DNPH colorimetric assay and immunofluorescence. Carbonylated protein content was significantly higher in elderly compared to young patients. One year after multidrug therapy (MDT) discharge and M. leprae clearance, oxidative damage increased in young L-Lep patients but not in elderly ones. Both elderly T and L-Lep patients present higher 4-HNE in cutaneous lesions than the young, mainly surrounding memory CD8+ T cells. Furthermore, young L-Lep demonstrated greater ability to neutralize ROS compared to elderly L-Lep patients, who presented lower gene expression of antioxidant enzymes, mainly glutathione peroxidase. CONCLUSIONS/SIGNIFICANCE: We conclude that elderly patients present exacerbated oxidative damage both in blood and in skin lesions and that age-related changes can be an important factor in leprosy immunopathogenesis. Ultimately, elderly patients could benefit from co-supplementation of antioxidants concomitant to MDT, to avoid worsening of the disease.


Assuntos
Hansenostáticos/uso terapêutico , Hanseníase/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Aldeídos , Antioxidantes , Carga Bacteriana , Brasil , Estudos de Casos e Controles , Quimioterapia Combinada , Feminino , Humanos , Hansenostáticos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae , Estresse Oxidativo , Carbonilação Proteica , Pele/metabolismo , Pele/patologia
13.
Indian J Dermatol Venereol Leprol ; 87(2): 207-213, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33769727

RESUMO

BACKGROUND: Due to the clinically poorly delineated unclear margin of extramammary Paget disease, the recurrence rate after surgical resection is high. AIMS: To compare photodynamic diagnosis and photodynamic plus reflectance confocal microscopy diagnosis in determining the tumor margins in patients with extramammary Paget disease. METHODS: Thirty-six patients with histopathologically confirmed primary extramammary Paget disease between January 2017 to June 2018 were included in the study. The skin lesion margins were preoperatively observed by the naked eye and with photodynamic diagnosis and photodynamic diagnosis plus reflectance confocal microscopy and they were compared to the postoperative histopathological examination results. RESULTS: Among the 130 sections taken from 36 patients, 83 sections (63.8%, 83/130) had tumor margins beyond the macroscopic line with a distance of 3.5 ± 3.1mm and a median of 2.7mm. Forty-six sections (35.4%, 46/130) exceeded the photodynamic diagnosis marker line with a distance of 2.1 ± 1.7mm and a median of 1.5mm. Twenty seven sections (20.8%, 27/130) were obtained beyond the photodynamic diagnosis plus reflectance confocal microscopy marker line with a distance of 1.4 ± 1.2mm and a median of 0.9mm. LIMITATIONS: Photodynamic diagnosis and reflectance confocal microscopy detection can be used to observe only the superficial margin of the tumor and not the deep part. Moreover, reflectance confocal microscopy was not used alone as a control. CONCLUSION: In terms of determining the extramammary Paget disease margin invasively, photodynamic diagnosis and photodynamic diagnosis plus reflectance confocal microscopy were found superior to observations made with the naked eye, while photodynamic diagnosis plus reflectance confocal microscopy was superior to photodynamic diagnosis alone.


Assuntos
Doença de Paget Extramamária/patologia , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Ácido Aminolevulínico/administração & dosagem , Feminino , Humanos , Luz , Masculino , Margens de Excisão , Microscopia Confocal , Pessoa de Meia-Idade , Doença de Paget Extramamária/cirurgia , Fármacos Fotossensibilizantes/administração & dosagem , Neoplasias Cutâneas/cirurgia
15.
J Manag Care Spec Pharm ; 27(4): 455-468, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33769850

RESUMO

BACKGROUND: Oral semaglutide is the first oral formulation of a glucagon-like peptide 1 (GLP-1) receptor agonist to be approved in the United States for glycemic control in people with type 2 diabetes mellitus (T2DM). While oral semaglutide is not indicated for reduction of cardiovascular event risk, its label does include evidence of no increase in cardiovascular risk in people who received oral semaglutide. OBJECTIVE: To estimate the incremental value of oral semaglutide added to existing antihyperglycemic treatment for people with T2DM with additional risk for cardiovascular disease. METHODS: We estimated the lifetime cost-effectiveness of oral semaglutide added to current antihyperglycemic treatment for T2DM using a microsimulation model based primarily on the UK Prospective Diabetes Study (UKPDS) Outcomes Model 2 (OM2) equations. Oral semaglutide added to current antihyperglycemic treatment was separately compared with (a) ongoing background antihyperglycemic treatment, (b) sitagliptin, (c) empagliflozin, and (d) liraglutide. Comparators sitagliptin, empagliflozin, and liraglutide were added to ongoing antihyperglycemic treatment. We applied hazard ratios derived from a network meta-analysis for cardiovascular and renal outcomes to the UKPDS OM2 estimated baseline rates. Health state utilities and costs were derived from the published literature. We estimated total costs, life-years (LYs), quality-adjusted life-years (QALYs), clinical events, and cost per major adverse cardiovascular event (MACE) avoided, over a lifetime time horizon using discount rates of 3% for costs and outcomes. RESULTS: The lifetime total cost for people treated with oral semaglutide was $311,300, with costs for the other comparators ranging from $262,800 (background treatment alone) to $287,800 (liraglutide). Oral semaglutide resulted in the fewest MACE, including the fewest cardiovascular deaths. Among the 5 modeled treatment strategies, oral semaglutide had the highest LYs gained (8.43 vs. 7.76 [background treatment alone] to 8.29 [empagliflozin and liraglutide]) and the highest QALYs gained (4.11 vs. 3.70 [background treatment alone] to 4.03 [empagliflozin]). Oral semaglutide would likely be considered cost-effective compared with liraglutide (incremental cost-effectiveness ratio [ICER] = $40,100), and moderately cost-effective versus background treatment alone ([ICER] = $117,500/QALY) and sitagliptin (ICER = $145,200/QALY). The ICER for oral semaglutide compared with empagliflozin was approximately $458,400 per QALY. CONCLUSIONS: As modeled, oral semaglutide as an add-on therapy to background antihyperglycemic treatment produced incremental benefits in MACE avoided, along with greater QALYs compared with background antihyperglycemic treatment alone. Oral semaglutide use resulted in better outcomes than background treatment alone or sitagliptin, and similar outcomes to liraglutide or empagliflozin with overlapping 95% confidence ranges for QALYs. Oral semaglutide was estimated to be cost-effective compared with liraglutide and to have incremental cost-effectiveness ratios between $100,000 and $150,000 per QALY versus sitagliptin and background therapy alone, but it did not meet these thresholds compared with empagliflozin. DISCLOSURES: Funding for this study was provided by the Institute for Clinical and Economic Review, an independent organization that evaluates the evidence on the value of health care interventions. ICER reports grants from Laura and John Arnold Foundation, California Health Care Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan. ICER's annual policy summit is supported by dues from AbbVie, Aetna, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, uniQure, and United Healthcare. Rind, Fazioli, Chapman, and Pearson are employed by ICER. Guzauskas and Hansen have nothing to disclose. Study results were presented at the New England Comparative Effectiveness Public Advisory Council (New England CEPAC), November 14, 2019, at Brown University, Providence, RI.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Hipoglicemiantes/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Custo-Benefício , Quimioterapia Combinada , Feminino , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/economia , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/economia , Masculino , Pessoa de Meia-Idade , Modelos Econômicos , Anos de Vida Ajustados por Qualidade de Vida , Estados Unidos , Adulto Jovem
16.
Front Immunol ; 12: 647385, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777045

RESUMO

Leprosy is an infectious disease that remains endemic in approximately 100 developing countries, where about 200,000 new cases are diagnosed each year. Moreover, multibacillary leprosy, the most contagious form of the disease, has been detected at continuously higher rates among Brazilian elderly people. Due to the so-called immunosenescence, characterized by several alterations in the quality of the immune response during aging, this group is more susceptible to infectious diseases. In view of such data, the purpose of our work was to investigate if age-related alterations in the immune response could influence the pathogenesis of leprosy. As such, we studied 87 individuals, 62 newly diagnosed and untreated leprosy patients distributed according to the age range and to the clinical forms of the disease and 25 healthy volunteers, who were studied as controls. The frequency of senescent and memory CD8+ leukocytes was assessed by immunofluorescence of biopsies from cutaneous lesions, while the serum levels of IgG anti-CMV antibodies were analyzed by chemiluminescence and the gene expression of T cell receptors' inhibitors by RT-qPCR. We noted an accumulation of memory CD8+ T lymphocytes, as well as reduced CD8+CD28+ cell expression in skin lesions from elderly patients, when compared to younger people. Alterations in LAG3 and PDCD1 gene expression in cutaneous lesions of young MB patients were also observed, when compared to elderly patients. Such data suggest that the age-related alterations of T lymphocyte subsets can facilitate the onset of leprosy in elderly patients, not to mention other chronic inflammatory diseases.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Senescência Celular/imunologia , Memória Imunológica , Imunossenescência/imunologia , Hanseníase/imunologia , Mycobacterium leprae , Dermatopatias/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Antígenos CD/genética , Estudos de Casos e Controles , Citomegalovirus/imunologia , Feminino , Expressão Gênica , Humanos , Imunoglobulina G/sangue , Hanseníase/sangue , Hanseníase/microbiologia , Hanseníase/patologia , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/genética , Pele/imunologia , Pele/patologia , Dermatopatias/sangue , Dermatopatias/microbiologia , Dermatopatias/patologia , Adulto Jovem
17.
Cardiovasc Intervent Radiol ; 44(5): 795-800, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33447924

RESUMO

PURPOSE: Endovascular robotics is an emerging technology within the developing field of medical robotics. This was a prospective evaluation to assess safety and feasibility of robotic-assisted carotid artery stenting. MATERIALS AND METHODS: Consecutive cases of carotid artery stenting cases performed over period of 24 months, from May 2015 to October 2016, using the Magellan Robotic System (Hansen, Mountain View, CA) were included. All cases utilised the robotic system to navigate the arch, obtain a stable position in the common carotid artery, followed by manual manipulation of Embolic Protection Devices and self-expandable stents through the robotic catheter. Patients demographics, clinical indications, anatomical features, technical and clinical success, complication rate and hospital stay were prospectively recorded. RESULTS: Thirteen patients, 10 males (78.5%), with an average age of 68.7 years were treated. Mean follow up time was 30 months. Ten patients (91%) were symptomatic at presentation. Anatomical indications for endovascular stent insertion were previous open surgery to the neck ± radiotherapy (87.5%) and hostile anatomy for open surgery (12.5%). Technical success was 100% and the robotic system demonstrates enhanced stability during arch and lesion crossing. There were no neurological complications post-operatively. Average hospital stay was 3 days (range 2-6 days) and a change in serum creatinine of -7.8 µmol/L. There was no documented case of in stent restenosis, new or worsening neurology during follow-up. CONCLUSION: These results illustrate safety and feasibility of robotic endovascular revascularisation for carotid disease and demonstrates potential to enhance peri-procedural safety through improved control and stability.


Assuntos
Artéria Carótida Primitiva/cirurgia , Estenose das Carótidas/cirurgia , Robótica , Stents , Procedimentos Cirúrgicos Vasculares/métodos , Idoso , Idoso de 80 Anos ou mais , Artéria Carótida Primitiva/diagnóstico por imagem , Estenose das Carótidas/diagnóstico , Angiografia por Tomografia Computadorizada , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
18.
PLoS Negl Trop Dis ; 15(1): e0008956, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33411800

RESUMO

BACKGROUND: After the elimination of leprosy in 1995, there were 10-30 newly detected leprosy cases every year in Zhejiang Province, and the epidemiological characteristics of the newly detected leprosy cases have changed. While most of the newly detected cases came from other provinces in China, not Zhejiang, it brought a new challenge for leprosy prevention and control in post- elimination era in Zhejiang, China. This study was aimed to understand the temporal-spatial distribution characteristics of newly detected leprosy cases, and provide the scientific rationales for the development of leprosy control strategy. METHODS: Data on the demographic of Zhejiang Province from 2011 to 2019 were obtained from the China Information System for Disease Control and Prevention, and the epidemiological data on leprosy cases newly detected in Zhejiang Province from 2011 to 2019 were obtained from the LEPROSY MANAGEMANT INFORMATION SYSTEM IN CHINA (LEPMIS), and temporal-spatial distributions were described. The geographic information system software-ArcGIS 10.4 was used to draw the statistical maps, and Geoda 1.14.0 was used for local spatial autocorrelation analysis (local Getis coefficient method). Ridley-Jopling classification was used to classify the clinical types into I, TT, BT, BB, BL or LL. Two-group classification system developed by the World Health Organization (WHO) was used and cases were classified into multibacillary (MB) type or paucibacillary (PB) type. RESULTS: A total of 167 leprosy cases were reported in Zhejiang Province during 2011-2019, including 107 cases in males and 60 in females. The mean age at diagnosis was 37.99±14.81 years, and 94.01% of the cases were detected through the examination at skin-clinics. The number of workers, MB cases, G2D cases were 81 (48.50%), 159 (94.01%), 24 (14.37%) respectively, and the rate of early detection increased from 45.16% in 2011 to 90.91% in 2019. Leprosy cases were reported in all the prefectures of Zhejiang except Zhoushan City. The cases in local population accounted for 23.35% (39 cases), and the cases in floating population (especially coming from high epidemic provinces in China) accounted for 76.65% (128 cases). The annual number of newly detected cases showed a decreasing trend, from 31 cases in 2011 to 11 in 2019. Time of the floating population living in Zhejiang Province ranged from several months to more than 10 years. The annual proportion of new cases with G2D declined from 22.58% in 2011 to 9.09% in 2019. The results of local indicators of autocorrelation (LISA) analysis showed that the high-high areas were mainly concentrated in the middle and northeast of Zhejiang Province, while the low-low areas were in the east and southwest. CONCLUSION: A few scattered cases still can be seen in post-elimination era, and there was a spatial clustering of the newly detected leprosy cases in Zhejiang Province. Most of the cases in Zhejiang Province were from other high epidemic provinces in China, which brought a new challenge for leprosy control and prevention in post- elimination era in Zhejiang, and it is also necessary to strengthen the early detection and standard management of the leprosy cases in floating population in Zhejiang.


Assuntos
Hanseníase/epidemiologia , Hanseníase/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China/epidemiologia , Cidades , Diagnóstico Precoce , Epidemias , Feminino , Sistemas de Informação Geográfica , Humanos , Hanseníase/diagnóstico , Masculino , Pessoa de Meia-Idade , Análise Espacial , Adulto Jovem
19.
PLoS Negl Trop Dis ; 15(1): e0009031, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33476343

RESUMO

BACKGROUND: Understanding how knowledge, attitudes and practices regarding leprosy differ in endemic countries can help us develop targeted educational and behavioural change interventions. This study aimed to examine the differences and commonalities in and determinants of knowledge, attitudes, practices and fears regarding leprosy in endemic districts in India and Indonesia. PRINCIPLE FINDINGS: A cross-sectional mixed-methods design was used. Persons affected by leprosy, their close contacts, community members and health workers were included. Through interview-administered questionnaires we assessed knowledge, attitudes, practices and fears with the KAP measure, EMIC-CSS and SDS. In addition, semi-structured interviews and focus group discussions were conducted. The quantitative data were analysed using stepwise multivariate regression. Determinants of knowledge and stigma that were examined included age, gender, participant type, education, occupation, knowing someone affected by leprosy and district. The qualitative data were analysed using open, inductive coding and content analysis. We administered questionnaires to 2344 participants (46% from India, 54% from Indonesia) as an interview. In addition, 110 participants were interviewed in-depth and 60 participants were included in focus group discussions. Knowledge levels were low in both countries: 88% of the participants in India and 90% of the participants in Indonesia had inadequate knowledge of leprosy. In both countries, cause, mode of transmission, early symptoms and contagiousness of leprosy was least known, and treatment and treatability of leprosy was best known. In both countries, health workers had the highest leprosy knowledge levels and community members the highest stigma levels (a mean score of up to 17.4 on the EMIC-CSS and 9.1 on the SDS). Data from the interviews indicated that people were afraid of being infected by leprosy. Local beliefs and misconceptions differed, for instance that leprosy is in the family for seven generations (Indonesia) or that leprosy is a result of karma (India). The determinants of leprosy knowledge and stigma explained 10-29% of the variability in level of knowledge and 3-10% of the variability in level of stigma. CONCLUSION: Our findings show the importance of investigating the perceptions regarding leprosy prior to educational interventions in communities: even though knowledge levels were similar, local beliefs and misconceptions differed per setting. The potential determinants we included in our study explained very little of the variability in level of knowledge and stigma and should be explored further. Detailed knowledge of local knowledge gaps, beliefs and fears can help tailor health education to local circumstances.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Hanseníase/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Índia/epidemiologia , Indonésia/epidemiologia , Masculino , Pessoa de Meia-Idade , Percepção , Estigma Social , Adulto Jovem
20.
Knee Surg Sports Traumatol Arthrosc ; 29(5): 1523-1534, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32761358

RESUMO

PURPOSE: To determine the incidence and location of osteochondral lesions (OCLs) following ankle fractures as well as to determine the association between fracture type and the presence of OCLs. Up to 50% of patients with ankle fractures that receive surgical treatment show suboptimal functional results with residual complaints at a long-term follow-up. This might be due to the presence of intra-articular osteochondral lesions (OCL). METHODS: A literature search was carried out in PubMed (MEDLINE), EMBASE, CDSR, DARE and CENTRAL to identify relevant studies. Two authors separately and independently screened the search results and conducted the quality assessment using the MINORS criteria. Available full-text clinical articles on ankle fractures published in English, Dutch and German were eligible for inclusion. Per fracture classification, the OCL incidence and location were extracted from the included articles. Where possible, OCL incidence per fracture classification (Danis-Weber and/or Lauge-Hansen classification) was calculated and pooled. Two-sided p values of less than 0.05 were considered statistically significant. RESULTS: Twenty articles were included with a total of 1707 ankle fractures in 1707 patients. When focusing on ankle fractures that were assessed directly after the trauma, the OCL incidence was 45% (n = 1404). Furthermore, the most common location of an OCL following an ankle fractures was the talus (43% of all OCLs). A significant difference in OCL incidence was observed among Lauge-Hansen categories (p = 0.049). Post hoc pairwise comparisons between Lauge-Hansen categories (with adjusted significance level of 0.01) revealed no significant difference (n.s.). CONCLUSION: OCLs are frequently seen in patients with ankle fractures when assessed both directly after and at least 12 months after initial trauma (45-47%, respectively). Moreover, the vast majority of post-traumatic OCLs were located in the talus (42.7% of all OCLs). A higher incidence of OCLs was observed with rotational type fractures. The clinical relevance of the present systematic review is that it provides an overview of the incidence and location of OCLs in ankle fractures, hereby raising awareness to surgeons of these treatable concomitant injuries. As a result, this may improve the clinical outcomes when directly addressed during index surgery. LEVEL OF EVIDENCE: IV.


Assuntos
Fraturas do Tornozelo/epidemiologia , Doenças das Cartilagens/epidemiologia , Cartilagem Articular/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Tornozelo/patologia , Fraturas do Tornozelo/cirurgia , Traumatismos do Tornozelo/epidemiologia , Traumatismos do Tornozelo/cirurgia , Articulação do Tornozelo/patologia , Doenças das Cartilagens/cirurgia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tálus/lesões , Tálus/cirurgia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA