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OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) primarily affects small vessels. Large-vessel involvement (LVI) is rare. We aimed to describe the characteristics of LVI, to identify associated risk factors, and to describe its therapeutic management. METHODS: This multicenter case-control (1:2) study included patients with AAV according to the ACR/EULAR classification and LVI as defined by the Chapel Hill nomenclature, together with controls matched for age, sex, and AAV type. RESULTS: We included 26 patients, 15 (58 %) of whom were men, with a mean age of 56.0 ± 17.1 years. The patients had granulomatosis with polyangiitis (n = 20), or microscopic polyangiitis (n = 6). The affected vessels included the aorta (n = 18; 69 %) supra-aortic trunks (n = 9; 35 %), lower-limb arteries (n = 5; 19 %), mesenteric arteries (n = 5; 19 %), renal arteries (n = 4; 15 %), and upper-limb arteries (n = 2; 8 %). Imaging showed wall thickening (n = 10; 38 %), perivascular inflammation (n = 8; 31 %), aneurysms (n = 5; 19 %), and stenosis (n = 4; 15 %). Comparisons with the control group revealed that LVI was significantly associated with neurological manifestations (OR=3.23 [95 % CI: 1.11-10.01, p = 0.03]), but not with cardiovascular risk factors (OR=0.70 [95 % CI: 0.23-2.21, p = 0.60]), or AAV relapse (OR=2.01 [95 % CI: 0.70-5.88, p = 0.16]). All patients received corticosteroids, in combination with an immunosuppressant in 24 (92 %), mostly cyclophosphamide (n = 10, 38 %) or rituximab (n = 9, 35 %). CONCLUSION: Regardless of distinctions based on vessel size, clinicians should consider LVI as a potential manifestation of AAV, with the aorta commonly affected. The risk of developing LVI appears to be greater for clinical phenotypes of AAV with neurological involvement. Standard AAV treatment can be used to manage LVI.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Estudos de Casos e Controles , Idoso , Adulto , Fatores de Risco , Imunossupressores/uso terapêuticoRESUMO
We aimed to evaluate whether the administration of riboflavin to septic animals reduces inflammation, oxidative stress, organ dysfunction, and mortality. C57BL/6 mice, 6-8 weeks old, were allocated to the study group (polymicrobial sepsis induced by cecal ligation and puncture (CLP) + antibiotic + iv riboflavin), control (CLP + antibiotic + iv saline), or naïve (non-operated controls). Serum concentrations of alanine aminotransferase (ALT), creatine kinase-MB (CK-MB), urea, and creatinine, and markers of inflammation [interleukin (IL)-6, tumor necrosis factor (TNF)-α, keratinocyte-derived chemokine (KC), and macrophage inflammatory protein (MIP)-2)], and oxidative stress (malondialdehyde (MDA) were measured 12 h after the experiment. Animal survival rates were calculated after 7 days. Means between groups were compared using linear regression models adjusted under the Bayesian approach. No significant difference was observed between control and study groups in serum concentrations of IL-6 (95% credible interval) (-0.35 to 0.44), TNF-α (-15.7 to 99.1), KC (-0.13 to 0.05), MIP-2 (-0.84 to 0.06), MDA (-1.25 to 2.53), or ALT (-6.6 to 11.5). Serum concentrations of CK-MB (-145.1 to -30.1), urea (-114.7 to -15.1), and creatinine (-1.14 to -0.01) were higher in the study group. Survival was similar in both groups (P=0.8). Therefore, the use of riboflavin in mice undergoing sepsis induced by CLP did not reduce inflammation, oxidative stress, organ dysfunction, or mortality compared with placebo.
Assuntos
Antioxidantes , Sepse , Animais , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Teorema de Bayes , Quimiocinas , Creatinina , Inflamação/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Modelos Teóricos , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Riboflavina/uso terapêutico , Sepse/tratamento farmacológico , Sepse/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , UreiaRESUMO
We aimed to evaluate whether the administration of riboflavin to septic animals reduces inflammation, oxidative stress, organ dysfunction, and mortality. C57BL/6 mice, 6-8 weeks old, were allocated to the study group (polymicrobial sepsis induced by cecal ligation and puncture (CLP) + antibiotic + iv riboflavin), control (CLP + antibiotic + iv saline), or naïve (non-operated controls). Serum concentrations of alanine aminotransferase (ALT), creatine kinase-MB (CK-MB), urea, and creatinine, and markers of inflammation [interleukin (IL)-6, tumor necrosis factor (TNF)-α, keratinocyte-derived chemokine (KC), and macrophage inflammatory protein (MIP)-2)], and oxidative stress (malondialdehyde (MDA) were measured 12 h after the experiment. Animal survival rates were calculated after 7 days. Means between groups were compared using linear regression models adjusted under the Bayesian approach. No significant difference was observed between control and study groups in serum concentrations of IL-6 (95% credible interval) (-0.35 to 0.44), TNF-α (-15.7 to 99.1), KC (-0.13 to 0.05), MIP-2 (-0.84 to 0.06), MDA (-1.25 to 2.53), or ALT (-6.6 to 11.5). Serum concentrations of CK-MB (-145.1 to -30.1), urea (-114.7 to -15.1), and creatinine (-1.14 to -0.01) were higher in the study group. Survival was similar in both groups (P=0.8). Therefore, the use of riboflavin in mice undergoing sepsis induced by CLP did not reduce inflammation, oxidative stress, organ dysfunction, or mortality compared with placebo.
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BACKGROUND: Primary cutaneous lymphomas (PCLs) are a heterogeneous group of T-cell (CTCL) and B-cell (CBCL) malignancies. Little is known about their epidemiology at initial presentation in Europe and about potential changes over time. OBJECTIVES: The aim of this retrospective study was to analyse the frequency of PCLs in the French Cutaneous Lymphoma Registry (GFELC) and to describe the demography of patients. METHODS: Patients with a centrally validated diagnosis of primary PCL, diagnosed between 2005 and 2019, were included. RESULTS: The calculated incidence was unprecedently high at 1·06 per 100 000 person-years. The number of included patients increased yearly. Most PCL subtypes were more frequent in male patients, diagnosed at a median age of 60 years. The relative frequency of rare CTCL remained stable, the proportion of classical mycosis fungoides (MF) decreased, and the frequency of its variants (e.g. folliculotropic MF) increased. Similar patterns were observed for CBCL; for example, the proportion of marginal-zone CBCL increased over time. CONCLUSIONS: Changes in PCL frequencies may be explained by the emergence of new diagnostic criteria and better description of the entities in the most recent PCL classification. Moreover, we propose that an algorithm should be developed to confirm the diagnosis of PCL by central validation of the cases.
Assuntos
Linfoma de Células B , Linfoma Cutâneo de Células T , Micose Fungoide , Neoplasias Cutâneas , Europa (Continente) , Humanos , Linfoma Cutâneo de Células T/epidemiologia , Masculino , Pessoa de Meia-Idade , Micose Fungoide/epidemiologia , Sistema de Registros , Estudos Retrospectivos , Neoplasias Cutâneas/epidemiologiaRESUMO
BACKGROUND: Anaplastic Kaposi's sarcoma (KS) is a rare form of KS characterized clinically by the development of a tumour mass with unusual local aggressiveness and histologically by a specific architecture and cytological morphology. A very small number of limited series in endemic countries have established characteristics common to these anaplastic forms of KS. We present five patients with an anaplastic form in a context of KS ongoing for several years in a non-endemic country. MATERIALS AND METHODS: We collected 5 cases of anaplastic KS followed in our department over a period of 20years. We describe the main developmental, clinical, virological and histological features. RESULTS: The cases involved 4 men and 1 woman whose mean age at diagnosis of anaplastic KD was 70years, with an average time of 25years between initial diagnosis of KD and anaplastic transformation. Our patients were all treated with chemotherapy and/or radiotherapy (RT) prior to diagnosis of anaplastic transformation. All patients had a tumour mass of the lower limbs developing in classically indolent KS with associated chronic lymphoedema. Progression was very aggressive locally with deep invasion of the soft tissues as well as osteoarticular involvement, without visceral dissemination. At present, three patients are dead, one patient is showing partial response, and one patient is in locoregional progression. Diagnosis of the disease was based on histopathological findings. The tumour cells were undifferentiated, pseudo-cohesive, and chiefly organized in sheets. The mitotic count was high (27 mitoses per 10 fields at high magnification). Necrosis was constant. DISCUSSION: To our knowledge, this is the first series describing anaplastic Kaposi's sarcoma in a non-endemic country. The severity of the prognosis, despite the absence of visceral dissemination, is related to the local aggressiveness of anaplastic KS and to its resistance to radiotherapy and chemotherapy, with amputation being required in certain cases.
Assuntos
Sarcoma de Kaposi/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Amputação Cirúrgica , Antineoplásicos/uso terapêutico , Terapia Combinada , Progressão da Doença , Feminino , Infecções por HIV/complicações , Herpesvirus Humano 8/isolamento & purificação , Humanos , Perna (Membro) , Linfedema/complicações , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Radioterapia Adjuvante , Sarcoma de Kaposi/terapia , Sarcoma de Kaposi/virologia , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/virologia , Carga ViralRESUMO
Neutrophilic eccrine hidradenitis (NEH) is a rare neutrophilic dermatosis, first described in patients undergoing chemotherapy for a malignant haemopathy. It has polymorphous clinical features and the association of both clinical and histological features is necessary to make a diagnosis. We report the first two cases of NEH in patients treated with a BRAF inhibitor (BRAFi), either dabrafenib or vemurafenib, for a stage IV metastatic melanoma. Disseminated erythematous plaques associated with fever and polyarthralgia occurred early after the initiation of treatment and were badly tolerated. Histological analyses confirmed the diagnosis of NEH. Symptoms disappeared a few days after the cessation of treatment and introduction of topical steroids. The replacement of one BRAFi with another is a therapeutic alternative as it is not necessarily associated with a relapse of NEH. NEH can be added to the spectrum of neutrophilic dermatoses induced by BRAFis. It occurs earlier (3-4 days) than previously described drug-induced NEH (9-12 days) and may be an earlier stage of eccrine squamous syringometaplasia, which has already been reported in the context of BRAFi-treated patients.
Assuntos
Antineoplásicos/efeitos adversos , Toxidermias/etiologia , Hidradenite/induzido quimicamente , Imidazóis/efeitos adversos , Indóis/efeitos adversos , Oximas/efeitos adversos , Sulfonamidas/efeitos adversos , Adulto , Feminino , Humanos , Masculino , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Vemurafenib , Adulto JovemRESUMO
BACKGROUND: Recent studies have independently implicated the chemokine CXCL12 and its receptors, CXCR4 and CXCR7, in the pathophysiology of Kaposi sarcoma (KS). OBJECTIVES: We investigated whether the CXCL12/CXCR4-CXCR7 protein trio could constitute KS biomarkers. METHODS: Endothelial and spindle cells positive for CXCL12/CXCR4-CXCR7, human herpesvirus-8 latency-associated nuclear antigen (LANA), Ki67 antigen (proliferation) and vascular endothelial growth factor (VEGF) were quantitated in skin lesions from patients with AIDS-associated KS, patients with classic KS and patients with angiomas, using immunohistochemistry and quantitative image analysis (16, 21 and 20 skin lesions, respectively). Plasma CXCL12 concentrations were measured by enzyme-linked immunosorbent assay from 20 patients with AIDS-KS, 12 HIV-infected patients without KS and 13 healthy donors' samples. RESULTS: Cells positive for CXCL12, CXCR4, CXCR7, LANA, Ki67 and VEGF were significantly enriched in patients with AIDS-associated KS and classic KS vs. angiomas (P < 0·001), and in nodular vs. macular/papular KS lesions (P < 0·05). CXCL12, CXCR4 and CXCR7 detection correlated with LANA, Ki67 and VEGF detection (r > 0·4; P < 0·05). However, plasma CXCL12 concentrations did not differ between patients with AIDS-associated KS, HIV-infected patients without KS, and healthy donors. CONCLUSIONS: The CXCL12/CXCR4-CXCR7 trio is upregulated in KS and correlates with KS pathophysiological markers and the severity of skin lesions. Histological assessment of the CXCL12 axis could serve as a valuable biomarker for KS diagnosis and progression.
Assuntos
Biomarcadores Tumorais/metabolismo , Quimiocina CXCL12/metabolismo , Receptores CXCR4/metabolismo , Receptores CXCR/metabolismo , Sarcoma de Kaposi/metabolismo , Neoplasias Cutâneas/metabolismo , Adulto , Inibidores da Angiogênese/uso terapêutico , Antígenos Virais/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Lenalidomida , Masculino , Proteínas Nucleares/metabolismo , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: Merkel cell polyomavirus (MCPyV) is the main aetiological agent of Merkel cell carcinoma (MCC). Serum antibodies against the major MCPyV capsid protein (VP1) are detected in the general population, whereas antibodies against MCPyV oncoproteins (T antigens) have been reported specifically in patients with MCC. OBJECTIVES: The primary aim was to assess whether detection of serum antibodies against MCPyV proteins at baseline was associated with disease outcome in patients with MCC. The secondary aim was to establish whether evolution of these antibodies during follow-up was associated with the course of the disease. METHODS: Serum T-antigen and VP1 antibodies were assessed by enzyme-linked immunosorbent assay using recombinant proteins in a cohort of 143 patients with MCC, including 84 patients with serum samples available at baseline. RESULTS: Low titres of VP1 antibodies at baseline (< 10 000) were significantly and independently associated with increased risk of recurrence [hazard ratio (HR) 2·71, 95% confidence interval (CI) 1·13-6·53, P = 0·026] and death (HR 3·74, 95% CI 1·53-9·18, P = 0·004), whereas T-antigen antibodies were not found to be associated with outcome. VP1 antibodies did not differ between patients in remission and those with recurrence or progression during follow-up. However, T-antigen antibodies were more frequently detected in patients with recurrence or progression at 12 months (P = 0·020) and 24 months (P = 0·016) after diagnosis. CONCLUSIONS: VP1 antibodies constitute a prognostic marker at baseline, whereas T-antigen antibodies constitute a marker of disease recurrence or progression if detected > 12 months after diagnosis.
Assuntos
Antígenos Virais de Tumores/sangue , Biomarcadores Tumorais/sangue , Proteínas do Capsídeo/sangue , Carcinoma de Célula de Merkel/imunologia , Neoplasias Cutâneas/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Célula de Merkel/mortalidade , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Poliomavírus das Células de Merkel/imunologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/mortalidade , Infecções por Polyomavirus/imunologia , Infecções por Polyomavirus/mortalidade , Prognóstico , Medição de Risco/métodos , Neoplasias Cutâneas/mortalidade , Infecções Tumorais por Vírus/imunologiaRESUMO
BACKGROUND: Microcystic adnexal carcinoma (MAC), syringomatous carcinoma (SC) and "Squamoid eccrine ductal carcinoma" (SEDC) are rare sclerosing adnexal tumours. OBJECTIVE: To understand the histogenesis of these tumours and possible clinical implications. METHODS: We conducted a retrospective study of 30 cases, 18 MAC, 5 SC and 7 SEDC reviewed and classified by a panel of dermatopathology experts, with immunohistochemical analysis of keratins, including K77, a new keratin specific of eccrine ducts, and PHLDA1 expressed in adnexal structures. RESULTS: There was a strong female predominance, with only five cases occurring in men. Patients with MAC and SC were younger (mean age 56 and 47 years) than those with SEDC (mean age 81 years). The most common localization was the cheek in SC and SEDC and the periocular area in MAC. Two cases of SEDC were found in organ transplant patients. No recurrence or metastases were observed after complete surgery of MAC, or SC (mean follow-up 7.2 years and 4.7 years), whereas one case of SEDC recurred and another could not be fully excised. MAC and SC had similar histological features, except for cysts. In MAC, calcifications, granulomas, connection to follicles, keratin expression pattern, PHLDA1 positivity and K77 negativity indicated a follicular histogenesis, whereas in SC, K77 positivity and keratin expression pattern were consistent with a differentiation towards eccrine apparatus. SEDC was composed of strands centred by ducts and nests with squamous differentiation and displayed K77 ductal positivity in all cases, a finding consistent with an eccrine origin. CONCLUSION: Our study demonstrated that MAC and SC have similar clinical characteristics, although histogenesis differs and show arguments for the individualization of SEDC.
Assuntos
Carcinoma/química , Carcinoma/patologia , Neoplasias Faciais/química , Neoplasias Faciais/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias das Glândulas Sudoríparas/química , Neoplasias das Glândulas Sudoríparas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/cirurgia , Neoplasias Faciais/cirurgia , Feminino , Humanos , Queratinas/análise , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias das Glândulas Sudoríparas/cirurgia , Fatores de Transcrição/análise , Adulto JovemRESUMO
BACKGROUND: Mycosis fungoides (MF) and pseudo-MF (or MF simulant) can be associated with B-cell malignancies, but distinction between a true neoplasm and a reactive process may be difficult. OBJECTIVES: To report seven patients with B-cell malignancy and folliculotropic MF or pseudo-MF and emphasize on criteria allowing distinction between the two conditions. METHODS: We retrospectively and prospectively included seven patients with B-cell malignancy who presented skin lesions histologically consisting in a folliculotropic T-cell infiltrate and reviewed the literature on the topic. RESULTS: Four men and three women had a chronic lymphocytic leukaemia (n = 6) or a MALT-type lymphoma (n = 1). Five patients had localized papules, and two had patches and plaques. Histological examination showed in all cases a diffuse dermal T-cell infiltrate with folliculotropic involvement and follicular mucinosis associated with clusters of the B-cell lymphoma, without significant expression of follicular helper T-cell markers. T-cell rearrangement studies showed a polyclonal pattern in the patients with papules and a monoclonal pattern in the cases of patches and plaques. Papular lesions had an indolent evolution, whereas patches and plaques persisted or worsened into transformed MF. CONCLUSION: Folliculotropic T-cell infiltrates associated with B-cell malignancies can be either a true folliculotropic MF or a pseudo-MF. The distinction between both conditions cannot rely only on the histopathological aspect, but needs both a clinical pathological correlation and the search for a dominant T-cell clone. Whether the neoplastic T and B cells derive from a common ancestor or the T-cell proliferation is promoted by the underlying B-cell lymphoma remains unsolved, but interaction between B and T cell in the skin does not appear to be dependent on a TFH differentiation of the T-cell infiltrate.
Assuntos
Leucemia Linfocítica Crônica de Células B/patologia , Linfoma de Zona Marginal Tipo Células B/patologia , Micose Fungoide/patologia , Pseudolinfoma/patologia , Neoplasias Cutâneas/patologia , Linfócitos T , Idoso , Diagnóstico Diferencial , Feminino , Folículo Piloso , Humanos , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/imunologia , Linfoma de Zona Marginal Tipo Células B/complicações , Linfoma de Zona Marginal Tipo Células B/imunologia , Masculino , Pessoa de Meia-Idade , Micose Fungoide/complicações , Estudos Prospectivos , Pseudolinfoma/complicações , Estudos Retrospectivos , Neoplasias Cutâneas/complicaçõesRESUMO
We report an imported case of Histoplasma capsulatum var. duboisii (H. duboisii) infection in a white French woman revealed by cutaneous lesions of the scalp, 18 years after her last stay in West and Central Africa. Asymptomatic bilateral pulmonary infiltrates were discovered on thoracic computed tomography. Skin biopsy allowed the positive diagnosis showing the typical yeasts; culture of biopsy specimens was positive for H. capsulatum. In the absence of criteria of severity, the patient was treated for one year with oral itraconazole 400mg/day. The outcome was favourable, skin and pulmonary lesions resolved slowly. The follow up is 5 years without relapse after the end of treatment. This case illustrates the possibility of late occurrence of H. duboisii infection, many years after exposure and the major importance of asking any patient for travelling or residency in tropical countries.
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Histoplasma , Histoplasmose/patologia , Pneumopatias Fúngicas/patologia , Dermatoses do Couro Cabeludo/patologia , Diagnóstico Tardio , Feminino , Histoplasma/isolamento & purificação , Histoplasmose/tratamento farmacológico , Histoplasmose/microbiologia , Humanos , Itraconazol/uso terapêutico , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/microbiologia , Pessoa de Meia-Idade , Dermatoses do Couro Cabeludo/tratamento farmacológico , Dermatoses do Couro Cabeludo/microbiologia , Fatores de Tempo , ViagemRESUMO
BACKGROUND: Merkel cell polyomavirus has been recognized to be associated with Merkel cell carcinoma (MCC), but the evolution of this cancer probably depends on various factors. Vitamin D deficiency, defined by serum 25-hydroxyvitamin D levels <50 nmol/L, seems to influence cancer behavior and progression, but has never been assessed in MCC patients. OBJECTIVES: First, to evaluate whether vitamin D deficiency was associated with tumor characteristics and prognosis in a cohort of MCC patients. Second, to assess expression of the vitamin D receptor (VDR) in MCC tumors. METHODS: Clinical findings, Merkel cell polyomavirus markers and vitamin D status were assessed in a cohort of French MCC patients. The study was limited to the 89 patients for whom the serum sample had been collected within 3 years after the diagnosis of MCC. Correlation between vitamin D deficiency and MCC characteristics and outcome were determined in regression analyses. VDR expression in MCC tumours was assessed by immunohistochemistry. RESULTS: Vitamin D deficiency was noted in 65.1% of the patients and was independently associated with greater tumor size at diagnosis (P = 0.006) and with metastasis recurrence (HR, 2.89; 95% CI, 1.03 to 8.13; P = 0.043), but not with death from MCC, although there was a trend (HR, 5.28; 95% CI, 0.75 to 36.96; P = 0.093). VDR was found to be strongly expressed in all 28 MCC tumor specimens investigated. CONCLUSION: The association between vitamin D deficiency and MCC characteristics and outcome, together with detection of the VDR in MCC cells, suggest that vitamin D could influence the biology of MCC.
Assuntos
Carcinoma de Célula de Merkel/complicações , Neoplasias Cutâneas/complicações , Deficiência de Vitamina D/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Célula de Merkel/patologia , Carcinoma de Célula de Merkel/terapia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Calcitriol/metabolismo , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Resultado do Tratamento , Vitamina D/sangue , Deficiência de Vitamina D/metabolismo , Deficiência de Vitamina D/patologiaRESUMO
The goal of this study was to examine the prevalence, assessment and management of pediatric pain in a public teaching hospital. The study sample consisted of 121 inpatients (70 infants, 36 children, and 15 adolescents), their families, 40 physicians, and 43 nurses. All participants were interviewed except infants and children who could not communicate due to their clinical status. The interview included open-ended questions concerning the inpatients’ pain symptoms during the 24 h preceding data collection, as well as pain assessment and pharmacological/non-pharmacological management of pain. The data were obtained from 100% of the eligible inpatients. Thirty-four children/adolescents (28%) answered the questionnaire and for the other 72% (unable to communicate), the family/health professional caregivers reported pain. Among these 34 persons, 20 children/adolescents reported pain, 68% of whom reported that they received pharmacological intervention for pain relief. Eighty-two family caregivers were available on the day of data collection. Of these, 40 family caregivers (49%) had observed their child’s pain response. In addition, 74% reported that the inpatients received pharmacological management. Physicians reported that only 38% of the inpatients exhibited pain signs, which were predominantly acute pain detected during clinical procedures. They reported that 66% of patients received pharmacological intervention. The nurses reported pain signs in 50% of the inpatients, which were detected during clinical procedures. The nurses reported that pain was managed in 78% of inpatients by using pharmacological and/or non-pharmacological interventions. The findings provide evidence of the high prevalence of pain in pediatric inpatients and the under-recognition of pain by health professionals.
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Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Avaliação em Enfermagem/estatística & dados numéricos , Medição da Dor , Manejo da Dor/métodos , Cuidadores , Hospitais de Ensino/estatística & dados numéricos , Padrões de Prática Médica , Prevalência , Dor/epidemiologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Post-radiation atypical vascular lesions of the skin display clinical and morphological overlap with well-differentiated angiosarcomas, and correct diagnosis may be difficult. PATIENTS AND METHODS: We studied clinical, histological and immuno-histochemical aspects (CD31, CD34, D2-40 and VEGFR-3) of eight post-radiation atypical vascular lesions comparatively with three post-radiation angiosarcomas. RESULTS: All patients were female and received radiation therapy for breast carcinoma. On average, atypical vascular lesions occurred 4.3 years after radiation therapy and presented as small papulonodules or erythematous plaques. The clinical course after simple excision was benign. Histologically, they were relatively circumscribed lesions and showed slit-like vessels dissecting dermal collagen in all cases. On average, angiosarcomas occurred 5 years after radiation therapy and presented as more extensive lesions with a more aggressive clinical course. The lesions showed histological overlap with atypical vascular lesions, but were poorly circumscribed, with deeper invasion, cytological atypia and mitosis. Although the immuno-histochemical profiles were similar, expression of VEGFR-3 was greater in two cases of angiosarcoma. CONCLUSION: Post-radiation atypical vascular lesions are benign lesions that display clinical, histological and immuno-phenotypic overlap with well-differentiated angiosarcoma, and diagnosis requires good clinicopathological correlation. VEGFR-3 may be useful for differential diagnosis, as well as amplification of the MYC gene.
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Hemangiossarcoma/etiologia , Hemangiossarcoma/patologia , Neoplasias Induzidas por Radiação/patologia , Lesões por Radiação/patologia , Dermatopatias Vasculares/etiologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , HumanosRESUMO
The objective of this study is to retrospectively report the results of interventions for controlling a vancomycin-resistant enterococcus (VRE) outbreak in a tertiary-care pediatric intensive care unit (PICU) of a University Hospital. After identification of the outbreak, interventions were made at the following levels: patient care, microbiological surveillance, and medical and nursing staff training. Data were collected from computer-based databases and from the electronic prescription system. Vancomycin use progressively increased after March 2008, peaking in August 2009. Five cases of VRE infection were identified, with 3 deaths. After the interventions, we noted a significant reduction in vancomycin prescription and use (75 percent reduction), and the last case of VRE infection was identified 4 months later. The survivors remained colonized until hospital discharge. After interventions there was a transient increase in PICU length-of-stay and mortality. Since then, the use of vancomycin has remained relatively constant and strict, no other cases of VRE infection or colonization have been identified and length-of-stay and mortality returned to baseline. In conclusion, we showed that a bundle intervention aiming at a strict control of vancomycin use and full compliance with the Hospital Infection Control Practices Advisory Committee guidelines, along with contact precautions and hand-hygiene promotion, can be effective in reducing vancomycin use and the emergence and spread of vancomycin-resistant bacteria in a tertiary-care PICU.
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Criança , Feminino , Humanos , Antibacterianos/administração & dosagem , Infecção Hospitalar/prevenção & controle , Enterococcus/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/prevenção & controle , Controle de Infecções/métodos , Resistência a Vancomicina , Vancomicina/administração & dosagem , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Surtos de Doenças , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Hospitais Universitários , Unidades de Terapia Intensiva Pediátrica , Avaliação de Programas e Projetos de Saúde , Estudos RetrospectivosRESUMO
Kaposi Sarcoma (KS) are opportunistic tumors, associated with human herpes virus 8 (HHV8) infection. KS development is highly favored by immune-depression and remains the second most frequent tumor in acquired immune deficiency syndrome patients. Although it has been shown that experimental expression of the HHV8 G-protein-coupled receptor (vGPCR) in the endothelial compartment is alone sufficient to recapitulate the formation and progression of KS-like lesions, its functional effects on endothelial homeostasis are not fully understood. Here we show that vGPCR expression in endothelial cells induces an increase in paracellular permeability both in vivo and in vitro. By using pharmacological inhibitors and small interference RNA-based knockdown, we demonstrate an essential role for the PI(3)Kinase-γ/Rac nexus in vGPCR-mediated permeability. This was further accompanied by dramatic remodeling of VE-cadherin-dependent cell-cell junctions. Importantly, this in vitro vGPCR-initiated signaling signature was observed in a large panel of human KS. Altogether, our results support the hypothesis that endothelial vGPCR signaling is co-opted in KS, and unveil new key cellular targets for therapeutic intervention.
Assuntos
Antígenos CD/metabolismo , Caderinas/metabolismo , Herpesvirus Humano 8 , Receptores de Quimiocinas/metabolismo , Sarcoma de Kaposi/virologia , Neoplasias Cutâneas/virologia , Síndrome da Imunodeficiência Adquirida/metabolismo , Síndrome da Imunodeficiência Adquirida/virologia , Androstadienos/farmacologia , Animais , Permeabilidade Capilar/efeitos dos fármacos , Linhagem Celular , Cromonas/farmacologia , Cinamatos/farmacologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/virologia , Inibidores Enzimáticos/farmacologia , Feminino , Furanos/farmacologia , Humanos , Indóis/farmacologia , Junções Intercelulares/efeitos dos fármacos , Junções Intercelulares/metabolismo , Camundongos , Camundongos Nus , Morfolinas/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Piridinas/farmacologia , Pirimidinas/farmacologia , Quinoxalinas/farmacologia , RNA Interferente Pequeno/genética , Sarcoma de Kaposi/tratamento farmacológico , Sarcoma de Kaposi/patologia , Pele/metabolismo , Pele/virologia , Neoplasias Cutâneas/tratamento farmacológico , Sulfonamidas/farmacologia , Tiazolidinedionas/farmacologia , WortmaninaRESUMO
BACKGROUND: a clinical study of 14 patients presenting both malignant melanoma and HIV infection, and analysis of the literature to determine the frequency and specific features of this association. PATIENTS AND METHODS: ten men and four women of median age 43 years were included. In 50% of cases, the primary melanoma consisted of spreading superficial melanoma with a mean Breslow thickness of 2.83 mm. In two cases, regional lymph node metastasis was discovered but with no primary melanoma being identified. HIV infection was already documented on diagnosis of melanoma in 11 cases, and it was discovered in three cases at the time of surgery for melanoma (treatment of the primary melanoma in two cases, and in one case, regional lymph node dissection two years after the initial diagnosis). Eight patients died within a mean period of 39 months, with melanoma being the cause of death in six cases. Following relapse of melanoma, the course of the disease was severe, with mean stage IV survival of 3.6 months. No response to chemotherapy was observed where such treatment was feasible. DISCUSSION: the presence of HIV appears to be an aggravating factor for the outcome of metastatic melanoma. CONCLUSION: our study suggests the importance of clinical examination of pigmented lesions in HIV patients in order to ensure early identification of melanoma.
Assuntos
Soropositividade para HIV/diagnóstico , Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adulto , Causas de Morte , Diagnóstico Precoce , Feminino , Soropositividade para HIV/mortalidade , Soropositividade para HIV/patologia , Humanos , Metástase Linfática/patologia , Masculino , Melanoma/mortalidade , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Taxa de SobrevidaRESUMO
BACKGROUND: Anti-tumor necrosis factor (TNF) agents are increasingly being used for a rapidly expanding number of rheumatic and systemic diseases. As a result of this use, and of the longer follow-up periods of treatment, there are a growing number of reports of the development of autoimmune processes related to anti-TNF agents. The use of anti-TNF agents has been associated with more and more cases of autoimmune diseases, principally cutaneous vasculitis, lupus-like syndrome, systemic lupus erythematosus and interstitial lung disease. OBSERVATIONS: We report 2 cases of autoimmune bullous skin disease occurring in patients undergoing TNF-targeted therapy: a bullous pemphigoid and a pemphigus foliaceus. Both patients were treated by anti-TNF agents for rheumatoid arthritis and showed improvement following interruption of that treatment. Here, we discuss the relationship between anti-TNF therapy and the occurrence of autoimmune bullous disease. CONCLUSION: Anti-TNF agents should be considered as a potential cause of drug-induced autoimmune bullous skin disease.