RESUMO
BACKGROUND: Daylight photodynamic therapy (DL-PDT) has become one of the most effective treatments for the resolution of actinic keratosis (AK) of Olsen grade 1 and 2. Generally, PDT it is carried out in a clinic setting, which involves the patient's and their caregivers commuting to the hospital as well as a significant use of resources to carry it out within the clinic setting. OBJECTIVES: To determine the efficacy and safety of a home-based treatment of AK with DL-PDT with the BF-200 ALA gel compared to a clinic-based setting. METHODS: The study was performed as a randomized, single-center, non-inferiority clinical trial with two parallel groups. 9 patients received one clinic-based DL-PDT (group 1) and 11 patients received one session of home-based DL-PDT (group 2). The primary endpoints were the mean AK clearance per patient and the total AK lesion clearance rate 12 weeks after treatment. The secondary endpoints were the number of remaining AKs and new AKs appearing in the treatment field 12 weeks after one PDT session. The pain during and 24 h after PDT as well as the local skin reactions were also assessed. RESULTS: The overall reduction of AK lesions per patient was similar in both groups with one PDT session. An overall AK clearance per patient of 10 ± 4.33 for group 1 versus 9.73 ± 2.9 for group 2 without statistically significant differences (p = 0.868). Regarding the clearance rate, although it was slightly higher in group 2 (71.58 ± 22.51 vs 82.1 ± 11.13), the analysis did not show statistically significant differences. The mild pain recorded during the treatment course and the mild local skin reactions were similar in both groups. Patient satisfaction was high for both groups without statistically significant differences. CONCLUSION: Self-performed home-based DL-PDT with BF-200 ALA gel is as effective as the one performed in a clinic-based setting, with a comparable safety profile, high levels of patient satisfaction and with advantages for the patients and their caregivers that can enhance patient´s adherence to the treatment.
Assuntos
Ácido Aminolevulínico , Ceratose Actínica , Fotoquimioterapia , Fármacos Fotossensibilizantes , Humanos , Ceratose Actínica/tratamento farmacológico , Ácido Aminolevulínico/uso terapêutico , Ácido Aminolevulínico/análogos & derivados , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Masculino , Feminino , Estudos Prospectivos , Idoso , Pessoa de Meia-Idade , Método Simples-Cego , Idoso de 80 Anos ou mais , EmulsõesRESUMO
BACKGROUND: Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCB), they have contributed to the exposure of women to persistent organic pollutants (POPs). These compounds can cross the placental barrier and interfere with the hormonal system of newborns. AIM: To determine concentrations of OCPs and PCBs and their xenoestrogenic activity in placentas of women from the PA-MAMI cohort of Panama. METHODS: Thirty-nine placenta samples from women in the Azuero peninsula (Panama) were analyzed. Five OCPs [p-p'-dichlorodiphenyldichloroethylene (p-p'-DDE), beta-hexachlorohexane (ß-HCH), γ-hexachlorohexane (lindane), hexachlorobenzene (HCB) and mirex] and three PCB congeners (PCB-138, PCB-153 and PCB-180) were quantified in placenta extracts. The xenoestrogenic activity of extracts was assessed with the E-Screen bioassay to estimate the total effective xenoestrogen burden (TEXB). RESULTS: All placental samples were positive for at least three POP residues and >70% for at least six. The frequencies of quantified OCPs ranged from 100% for p,p'-DDE and HCB to 30.8% for ß-HCH. The highest median concentration was for lindane (380.0 pg/g placenta), followed by p,p'-DDE (280.0 pg/g placenta), and HCB (90.0 pg/g placenta). Exposure to p,p'-DDE was associated with greater meat consumption, suggesting that animal fat is a major source of exposure to DDT metabolites. The frequency of detected PCBs ranged between 70 and 90%; the highest median concentration was for PCB 138 (17.0 pg/g placenta), followed by PCB 153 (16.0 pg/g placenta). All placentas were positive in the estrogenicity bioassay with a median TEXB-α of 0.91 pM Eeq/g of placenta. Exposure to lindane was positively associated with the xenoestrogenicity of TEXB- α, whereas this association was negative in the case of exposure to PCB 153. CONCLUSIONS: To our best knowledge, this study contributes the first evidence on the presence of POPs and xenoestrogenic burden in placentas from Latin-American women. Given concerns about the consequences of prenatal exposure to these compounds on children's health, preventive measures are highly recommended to eliminate or minimize the risk of OCP exposure during pregnancy.
Assuntos
Poluentes Ambientais , Hidrocarbonetos Clorados , Praguicidas , Bifenilos Policlorados , Recém-Nascido , Animais , Feminino , Humanos , Gravidez , Bifenilos Policlorados/análise , Hexaclorocicloexano/análise , Hexaclorocicloexano/metabolismo , Diclorodifenil Dicloroetileno , Hexaclorobenzeno/análise , DDT/análise , Placenta/química , Hidrocarbonetos Clorados/análise , Praguicidas/análise , Poluentes Ambientais/análise , Relações Mãe-FilhoRESUMO
OBJECTIVE: Imipenem is recommended in patients with chemotherapy-induced febrile neutropenia. Although alterations of antibiotic pharmacokinetic parameters have been reported in such patients, little data is available on imipenem. METHODS: Prospective, single-center, non-interventional pharmacokinetic cohort study in adults with chemotherapy-induced febrile neutropenia. Critically ill patients were excluded. Imipenem was administered as a 30-min infusion of 1000 mg/8h. Total imipenem plasma concentrations were assayed by high-performance liquid chromatography during neutropenia and just after neutrophil recovery. We estimated population pharmacokinetic parameters of imipenem by non-linear mixed-effect modelling using the SAEM algorithm. RESULTS: Sixteen patients were included in the study, including nine women (56.3%), median age 37 years (range, 18.3; 78.3). Eight patients had an hematological malignancy (50.0%) and seven had a solid tumor (43.8%). Imipenem pharmacokinetics were best described by a one-compartment model with first-order elimination. Mean values for imipenem were: clearance 14.3L/h and 10.9L/h and volume of distribution 20.7L and 14.5 L during neutropenia and after recovery, respectively. Imipenem plasma area under the curve at steady state was reduced by 23% during neutropenia. However, all patients achieved a pharmacodynamic target of %fT>MIC ≥ 40% with a regimen of 1000 mg/8 h or 500 mg/6 h, for MICs up to 2 mg/L. The pharmacodynamics profile for a target of %fT > MIC = 100% was however less favorable with 500 mg/6 h or 1000 mg/8 h either during or after neutropenia. CONCLUSION: Pharmacokinetic/pharmacodynamic goals for imipenem were similar in patients during and after neutropenia, despite reduced plasma exposure.
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Neutropenia Febril Induzida por Quimioterapia , Imipenem , Humanos , Adulto , Feminino , Imipenem/uso terapêutico , Imipenem/farmacocinética , Neutropenia Febril Induzida por Quimioterapia/tratamento farmacológico , Estudos Prospectivos , Estudos de Coortes , Antibacterianos/uso terapêuticoRESUMO
Hydrochlorothiazide and other thiazide diuretics have been used for decades to treat high blood pressure, heart failure, and chronic kidney disease. Thiazides have been linked to photosensitivity with heterogeneous clinical manifestations and recovery times. Diagnosis can be aided by phototesting, photopatch testing, and skin biopsy. Long-term use of hydrochlorothiazide has been linked to an increased dose-dependent risk of certain types of skin cancer in recent years. In this review, we also look at other less common or lesser-known adverse effects of thiazide diuretics that have been described in isolated reports.
Assuntos
Hipertensão , Tiazidas , Anti-Hipertensivos/uso terapêutico , Dermatologistas , Humanos , Hidroclorotiazida/efeitos adversos , Hipertensão/tratamento farmacológico , Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico , Tiazidas/efeitos adversosRESUMO
INTRODUCTION: Penile fracture (PF) is a urological emergency with low incidence, and evidence of its long-term outcomes is scarce. This study focuses on postoperative complications and long-term functional outcomes in patients with PF and surgical repair at our center. MATERIALS AND METHOD: Clinical records of patients undergoing urgent surgery for PF at a third level hospital between 2006 and 2020 were retrospectively reviewed. Functional outcomes were assessed with voluntary telephone interviews from June 2020 to February 2021. Lower urinary tract symptoms were screened by IPSS questionnaire, sexual function by EHS and IIEF-5 and morphological alterations by direct questions to patients. RESULTS: A total of 41 patients underwent surgery for PF. Eleven of them also had urethral injury (higher incidence if there was bilateral corpora cavernosa injury, 19.4% vs. 80%, pâ¯<â¯0.05). Only 1 patient presented a Clavien-Dindo type 3a complication due to wound dehiscence, 4 (13%) type 2 and 9 (29%) type 1. Twenty-four patients underwent long-term follow-up, of whom 20 (83.3%) presented normal sexual function. Twelve patients (50%) had a palpable nodule at the fracture site, 8 (33.3%) had new onset penile curvature and 1 patient with previous urethral injury presented urethral stricture. CONCLUSION: In cases of penile fracture, there is a higher incidence of urethral injury if both corpora cavernosa are affected. Long-term functional sequelae after surgical repair of a PF are rare.
Assuntos
Pênis , Humanos , Masculino , Pênis/lesões , Pênis/cirurgia , Estudos Retrospectivos , Uretra/cirurgia , Estreitamento Uretral/etiologiaRESUMO
INTRODUCTION: Teledermatology (TD) is a health tool based on the application of information and communication technologies (ICT) for the care of skin diseases at a distance, allowing a better connection between primary care professionals (PCP) and specialized care. The objective of this study was to analyze the characteristics of the teleconsultations made to our service in a period of 2years (January 1, 2018 to December 31, 2019). MATERIAL AND METHODS: The data was obtained from a TD system with dermoscopy that allows teleconsultations to be carried out asynchronously. Data were analyzed over 24months. The variables studied were the health centre of origin, the diagnostic suspicion of the PCP, the time and type of response, and the clinical judgment issued by the dermatologist. RESULTS: Between January 1, 2018 and December 31, 2019, a total of 3,294 teleconsultations were received. 24.76% were referred to the dermatology consultation, while 25.63% required subsequent follow-up electronically. The most frequent diagnostic suspicion by the PCP was that of benign pathology (54.71%). The most frequent dermatological clinical judgment was that of seborrheic keratosis (20.19%), followed by actinic keratosis (14.02%), acquired common melanocytic nevi (13.24%) and basal cell carcinoma (8.98%). CONCLUSIONS: The TD system is a useful tool that allowed a quick response to a high percentage of consultations, helping to avoid unnecessary referrals and easy communication between primary and specialized care. It also allows prioritizing those patients with malignant tumour pathology.
Assuntos
Dermatologia , Consulta Remota , Dermatopatias , Humanos , Nevo Pigmentado , Neoplasias Cutâneas , EspanhaRESUMO
In this placebo-controlled phase II randomized clinical trial, 103 human immunodeficiency virus type 1 (HIV-1)-infected patients under cART (combined antiretroviral treatment) were randomized 2:1 to receive either 3 doses of DNA GTU-MultiHIV B (coding for Rev, Nef, Tat, Gag, and gp160) at week 0 (W0), W4, and W12, followed by 2 doses of LIPO-5 vaccine containing long peptides from Gag, Pol, and Nef at W20 and W24, or placebo. Analytical treatment interruption (ATI) was performed between W36 to W48. At W28, vaccinees experienced an increase in functional CD4+ T-cell responses (P < 0.001 for each cytokine compared to W0) measured, predominantly against Gag and Pol/Env, and an increase in HIV-specific CD8+ T cells producing interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-α) (P = 0.001 and 0.013, respectively), predominantly against Pol/Env and Nef. However, analysis of T-cell subsets by mass cytometry in a subpopulation showed an increase in the W28/W0 ratio for memory CD8+ T cells coexpressing exhaustion and senescence markers such as PD-1/TIGIT (P = 0.004) and CD27/CD57 (P = 0.044) in vaccinees compared to the placebo group. During ATI, all patients experienced viral rebound, with the maximum observed HIV RNA level at W42 (median, 4.63 log10 copies [cp]/ml; interquartile range [IQR], 4.00 to 5.09), without any difference between arms. No patient resumed cART for CD4 cell count drop. Globally, the vaccine strategy was safe. However, a secondary HIV transmission during ATI was observed. These data show that the prime-boost combination of DNA and LIPO-5 vaccines elicited broad and polyfunctional T cells. The contrast between the quality of immune responses and the lack of potent viral control underscores the need for combined immunomodulatory strategies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01492985.)IMPORTANCE In this placebo-controlled phase II randomized clinical trial, we evaluated the safety and immunogenicity of a therapeutic prime-boost vaccine strategy using a recombinant DNA vaccine (GTU-MultiHIV B clade) followed by a boost vaccination with a lipopeptide vaccine (HIV-LIPO-5) in HIV-infected patients on combined antiretroviral therapy. We show here that this prime-boost strategy is well tolerated, consistently with previous studies in HIV-1-infected individuals and healthy volunteers who received each vaccine component individually. Compared to the placebo group, vaccinees elicited strong and polyfunctional HIV-specific CD4+ and CD8+ T-cell responses. However, these immune responses presented some qualitative defects and were not able to control viremia following antiretroviral treatment interruption, as no difference in HIV viral rebound was observed in the vaccine and placebo groups. Several lessons were learned from these results, pointing out the urgent need to combine vaccine strategies with other immune-based interventions.
Assuntos
Vacinas contra a AIDS , Antirretrovirais/uso terapêutico , Infecções por HIV/terapia , Vacinas de DNA , Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/imunologia , Adulto , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Infecções por HIV/imunologia , HIV-1/efeitos dos fármacos , Humanos , Imunização Secundária , Masculino , Pessoa de Meia-Idade , Vacinas de DNA/administração & dosagem , Vacinas de DNA/imunologiaRESUMO
Eimeria ninakohlyakimovae represents a highly pathogenic coccidian parasite causing severe haemorrhagic typhlocolitis in goat kids worldwide. NETosis was recently described as an efficient defense mechanism of polymorphonuclear neutrophils (PMN) acting against different parasites in vitro and in vivo. In vitro interactions of caprine PMN with parasitic stages of E. ninakohlyakimovae (i. e. oocysts and sporozoites) as well as soluble oocyst antigens (SOA) were analyzed at different ratios, concentrations and time spans. Extracellular DNA staining was used to illustrate classical molecules induced during caprine NETosis [i. e. histones (H3) and neutrophil elastase (NE)] via antibody-based immunofluorescence analyses. Functional inhibitor treatments with DPI and DNase I were applied to unveil role of NADPH oxidase (NOX) and characterize DNA-backbone composition of E. ninakohlyakimovae-triggered caprine NETosis. Scanning electron microscopy (SEM)- and immunofluorescence-analyses demonstrated that caprine PMN underwent NETosis upon contact with sporozoites and oocysts of E. ninakohlyakimovae, ensnaring filaments which firmly entrapped parasites. Detailed co-localization studies of E. ninakohlyakimovae-induced caprine NETosis revealed presence of PMN-derived DNA being adorned with nuclear H3 and NE corroborating molecular characteristics of NETosis. E. ninakohlyakoimovae-induced caprine NETosis was found to be NOX-independent since DPI inhibition led to a slight decrease of NETosis. Exposure of caprine PMN to vital E. ninakohlyakimovae sporozoites as well as SOA resulted in up-regulation of IL-12, TNF-α, IL-6, CCL2 and iNOS gene transcription in stimulated PMN. Since vital E. ninakohlyakimovae-sporozoites induced caprine NETosis, this effective entrapment mechanism might reduce initial sporozoite epithelial host cell invasion during goat coccidiosis ultimately resulting in less macromeront formation and reduced merozoites I production.
Assuntos
Coccidiose/veterinária , Citocinas/genética , Eimeria/imunologia , Doenças das Cabras/parasitologia , Neutrófilos/parasitologia , Análise de Variância , Animais , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Coccidiose/imunologia , Coccidiose/parasitologia , Colite/parasitologia , Colite/veterinária , Citocinas/metabolismo , Eimeria/genética , Eimeria/ultraestrutura , Hemorragia Gastrointestinal/parasitologia , Hemorragia Gastrointestinal/veterinária , Doenças das Cabras/imunologia , Cabras , Interleucina-12/genética , Interleucina-12/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Microscopia Eletrônica de Varredura/veterinária , NADPH Oxidases/metabolismo , Neutrófilos/imunologia , Neutrófilos/ultraestrutura , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Oocistos/genética , Oocistos/imunologia , Reação em Cadeia da Polimerase/veterinária , Esporozoítos/genética , Esporozoítos/imunologia , Transcrição Gênica , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Tiflite/parasitologia , Tiflite/veterinária , Regulação para CimaRESUMO
BACKGROUND: Quantitative PCR to detect Pneumocystis jirovecii (Pj) is a new tool for the diagnosis of Pneumocystis jirovecii pneumonia (PJP). The yield of this technique, in cases of low fungal burden, when the standard technique using immunofluorescence (IF) is negative, needs to be evaluated. METHODS: We retrospectively reviewed the charts of all patients with a positive PCR but negative IF test (PCR+/IF-) in bronchoalveolar lavage (BAL) fluid performed over one year. We used an algorithm based on underlying immunosuppression, clinical picture, thoracic CT scan appearances, existence of an alternative diagnosis and the patient's outcome on treatment. Using this, each case was classified as probable PJP, possible PJP or colonization. RESULTS: Among the 416 BAL performed, 48 (12%) were PCR+/IF- and 43 patients were analyzed. Patients were mostly male (56%) with a median age of 60 years. Thirty-five (84%) were immunocompromised: 4 (9%) HIV-infected patients, 26 (60%) with hematologic or solid organ cancer, 3 (7%) were renal transplant recipients. Seven (16%) were classified as probable PPJ and 9 (21%) as possible PJP. Patients with a probable or possible PJP were more frequently admitted to the ICU (P<0.02) and had higher risk of death (P<0.01) when compared to those with colonization. Median PCR levels were very low and were not different between PJP or colonized patients (P=0.23). CONCLUSIONS: Among patients with a positive Pj PCR in BAL but with negative IF, only 37% had probable or possible PJP and PCR could not discriminate PJP from colonization.
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Líquido da Lavagem Broncoalveolar/microbiologia , Infecções Fúngicas Invasivas/diagnóstico , Infecções por Pneumocystis/diagnóstico , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Infecções por HIV/complicações , Infecções por HIV/microbiologia , Humanos , Hospedeiro Imunocomprometido , Infecções Fúngicas Invasivas/microbiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/epidemiologia , Neoplasias/microbiologia , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/microbiologia , Infecções por Pneumocystis/microbiologia , Infecções por Pneumocystis/patologia , Pneumocystis carinii/genética , Pneumonia por Pneumocystis/genética , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase em Tempo Real/normas , Estudos Retrospectivos , Transplantados/estatística & dados numéricosRESUMO
SETTING: Tuberculosis (TB) is a potential trigger of haemophagocytic syndrome (HS) but little is known about the features of TB-associated HS.OBJECTIVE: To assess the risk factors associated with HS in patients with TB.DESIGN: We performed a multicentre case-control study assessing the medical records of adult patients diagnosed with proven TB with (TB/HS+) or without (TB/HS-) associated HS.RESULTS: Twenty-one patients with TB/HS+ (24% women, median age, 37 years [IQR 30-48]) were included in the study. Eleven patients (52%) were infected with human immunodeficiency virus and seven patients (33%) were immunocompromised due to other reasons. TB was disseminated in 17 patients (81%). Compared with 50 control TB patients (TB/HS-), patients with TB/HS+ were more likely to be immunocompromised (86% vs. 18%; P < 0.001) and to present with disseminated TB (80% vs. 12%; P < 0.001). The outcome was poorer in patients with TB/HS+, with a higher admission rate to intensive care (71% vs. 0%; P < 0.001) and a higher risk of death (38% vs. 7%; P = 0.005).CONCLUSION: TB/HS+ occurred more likely in immunocompromised patients and severely impaired the prognosis of TB. Further studies are needed to devise therapeutic strategies for patients with TB/HS+.
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Infecções por HIV , Linfo-Histiocitose Hemofagocítica , Tuberculose , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Hospedeiro Imunocomprometido , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/epidemiologia , Masculino , Fatores de Risco , Tuberculose/complicações , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológicoRESUMO
Bisphenol A (BPA) is a high-production-volume chemical with endocrine disrupting properties commonly used as color developer in thermal paper. Concerns about the potential hazards of human BPA exposure have led to the increasing utilization of alternatives such as bisphenol S (BPS) and bisphenol F (BPF). This study was designed to assess: (i) BPA, BPS, and BPF concentrations in 112 thermal paper receipts from Brazil, France, and Spain by liquid chromatography coupled to mass spectrometry (LC-MS); and (ii) hormone-like activities of these receipts using two receptor-specific bioassays, the E-Screen for (anti-)estrogenicity and PALM luciferase assay for (anti-)androgenicity. BPA was present in 95.3% of receipts from Spain, 90.9% of those from Brazil, and 51.1% of those from France at concentrations up to 20.27â¯mg/g of paper. Only two samples from Brazil, two from Spain, and ten from France had a BPS concentration ranging from 6.46 to 13.29â¯mg/g; no BPA or BPS was detected in 27.7% of French samples. No BPF was detected in any receipt. Estrogenic activity was observed in all samples from Brazil and Spain and in 74.5% of those from France. Anti-androgenic activity was observed in >â¯90% of samples from Brazil and Spain and in 53.2% of those from France. Only 25.5% of French samples were negative for both estrogenic and anti-androgenic activity. Estrogenic and anti-androgenic activities per gram of paper were up to 1.411⯵M estradiol (E2) equivalent units (E2eq) and up to 359.5â¯mM procymidone equivalent units (Proceq), respectively. BPA but not BPS concentrations were positively correlated with both estrogenic and anti-androgenic activities. BPA still dominates the thermal paper market in Brazil and Spain, and BPS appears to be one of the main alternatives in France. There is an urgent need to evaluate the safety of alternatives proposed to replace BPA as developer in thermal printing. The large proportion of samples with hormonal activity calls for the adoption of preventive measures.
Assuntos
Compostos Benzidrílicos/análise , Papel , Fenóis/análise , Sulfonas/análise , Brasil , Monitoramento Ambiental , Estrogênios , França , Humanos , EspanhaAssuntos
Neoplasias do Ânus/cirurgia , Carcinoma de Células Escamosas/cirurgia , Colostomia/métodos , Infecções por HIV/diagnóstico , Retalho Miocutâneo/transplante , Recidiva Local de Neoplasia/cirurgia , Adulto , Neoplasias do Ânus/complicações , Neoplasias do Ânus/diagnóstico por imagem , Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Infecções por HIV/complicações , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Períneo/cirurgia , Prognóstico , Terapia de Salvação/métodos , Resultado do Tratamento , Recusa do Paciente ao TratamentoRESUMO
The aim of preventive measures against human immunodeficiency virus (HIV) is to reduce the incidence of HIV infection in the general population and in high-risk groups, such as men having sex with men (MSM), and to reduce the risk that a given individual will contract or spread the virus. Male and female condoms, post-exposure prophylaxis and circumcision are preventive methods currently recognized or promoted worldwide. Although modest success has been reported in a phase-III vaccine trial, other methods are being evaluated, such as vaginal and rectal microbicides, and pre-exposure prophylaxis (PrEP). Herein, we discuss results from prevention trials, especially those focusing on PrEP and particularly on recent results from 'on-demand' PrEP regimens. The efficacy of PrEP (rates of 0%-86%) is strongly correlated with adherence and plasma concentrations of antiretrovirals. Adverse events are rare. Selection of emtricitabine-resistant strains is mainly reported in individuals with an undiagnosed HIV infection using PrEP. PrEP is now strongly recommended in WHO prevention programmes for individuals at substantial risk for HIV with a view to controlling this epidemic by 2030.
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Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição , Animais , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Quimioprevenção , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Farmacorresistência Viral , Quimioterapia Combinada , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Adesão à Medicação , Resultado do TratamentoRESUMO
Extracellular trap (ET) formation has been demonstrated as novel effector mechanism against diverse pathogens in polymorphonuclear neutrophils (PMN), eosinophils, mast cells, macrophages and recently also in monocytes. In the current study, we show that E. ninakohlyakimovae triggers the deliverance of monocyte-derived ETs in vitro. Fluorescence illustrations as well as scanning electron microscopy (SEM) analyses showed that monocyte-derived ET formation was rapidly induced upon exposure to viable sporozoites, sporocysts and oocysts of E. ninakohlyakimovae. Classical features of monocyte-released ETs were confirmed by the co-localization of extracellular DNA adorned with myeloperoxidase (MPO) and histones (H3) in parasite-entrapping structures. The treatment of caprine monocyte ET structures with NADPH oxidase inhibitor diphenylene iodondium (DPI) significantly reduced ETosis confirming the essential role of reactive oxygen species (ROS) in monocyte mediated ETs formation. Additionally, co-culture of monocytes with viable sporozoites and soluble oocyst antigen (SOA) induced distinct levels of cytokine and chemokine gene transcription. Thus, the transcription of genes encoding for IL-12 and TNF-α was significantly upregulated after sporozoite encounter. In contrast IL-6 and CCL2 gene transcripts were rather weakly induced by parasites. Conversely, SOA only induced the up-regulation of IL-6 and CCL2 gene transcription, and failed to enhance transcripts of IL-12 and TNF-α in vitro. We here report on monocyte-triggered ETs as novel effector mechanism against E. ninakohlyakimovae. Our results strongly suggest that monocyte-mediated innate immune reactions might play an important role in early host immune reactions against E. ninakohlyakimovae in goats.
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Citocinas/metabolismo , Eimeria/classificação , Regulação da Expressão Gênica/imunologia , Monócitos/fisiologia , NADPH Oxidases/metabolismo , Animais , Células Cultivadas , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Citocinas/genética , Doenças das Cabras/parasitologia , Cabras , Interleucina-12/genética , Interleucina-12/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Monócitos/ultraestrutura , NADPH Oxidases/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Regulação para CimaRESUMO
BACKGROUND: Bloodstream infections (BSI) are frequent and potentially severe complications in allogeneic hematopoietic stem cell transplant (AHSCT) recipients. In patients on steroids, surveillance blood cultures (SBCs) are routinely performed to detect asymptomatic BSI but their usefulness remains controversial. METHODS: We performed a 1-year, observational, prospective, single-center study to assess the utility of daily SBCs in AHSCT recipients on steroids and a case-control study to identify risk factors associated with positive SBCs. All blood cultures (BCs) obtained from adults hospitalized in the HSCT unit were prospectively studied throughout 1 year. Characteristics, treatments, and outcome of patients were retrieved from medical charts. RESULTS: A total of 3594 BCs were obtained in 177 patients, including 1450 SBCs in 82 AHSCT recipients on steroids. In 33 patients, 103 SBCs (7%) were positive. Low-virulence bacteria were identified in 74% of episodes. When analyzing first episode of positive SBCs (28 patients), 6 (21%) true BSI were identified. CONCLUSIONS: Patients with positive SBCs were receiving antibiotic treatment less frequently at the time of SBCs (P < 0.001) and had more frequently BCs obtained through central venous access (P < 0.04) when compared to patients with negative SBCs. Daily SBCs in AHSCT recipients on steroids only rarely identify BSI and clear benefit for patients could not be demonstrated.
Assuntos
Antibacterianos/uso terapêutico , Infecções Assintomáticas/terapia , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Hemocultura/métodos , Glucocorticoides/efeitos adversos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adulto , Idoso , Antibacterianos/administração & dosagem , Bacteriemia/microbiologia , Bacteriemia/prevenção & controle , Estudos de Casos e Controles , Estudos de Viabilidade , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
CLINICAL CASE: An 82-year-old man was admitted to the emergency department complaining of a sudden painless visual loss in his left eye (OS). He was diagnosed with branch retinal artery occlusion (BRAO) with a visible embolus. In 2012, he had a central artery occlusion (CRAO) in his right eye (OD). An embolysis with Nd:YAG laser was attempted, the retinal arterial blood flow was restored completely and the visual field was improved, with no secondary complications. CONCLUSIONS: Nd:YAG laser embolysis is a treatment to be considered in patients with BRAO with a visible embolus. The risks and benefits of the procedure should be evaluated, comparing it with possible permanent loss of visual acuity and other vascular complications caused by BRAO.