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BACKGROUND: Approved on-demand treatments for hereditary angioedema attacks need to be administered parenterally, a route of administration that is associated with delays in treatment or withholding of therapy. METHODS: In this phase 3, double-blind, three-way crossover trial, we randomly assigned participants at least 12 years of age with type 1 or type 2 hereditary angioedema to take up to two oral doses of sebetralstat (300 mg or 600 mg) or placebo for an angioedema attack. The primary end point, assessed in a time-to-event analysis, was the beginning of symptom relief, defined as a rating of "a little better" on the Patient Global Impression of Change scale (ratings range from "much worse" to "much better") at two or more consecutive time points within 12 hours after the first administration of the trial agent. Key secondary end points, assessed in a time-to-event analysis, were a reduction in attack severity (an improved rating on the Patient Global Impression of Severity [PGI-S] scale, with ratings ranging from "none" to "very severe") at two or more consecutive time points within 12 hours and complete attack resolution (a rating of "none" on the PGI-S scale) within 24 hours. RESULTS: A total of 136 participants were assigned to one of six trial sequences, with 110 treating 264 attacks. The time to the beginning of symptom relief with the 300-mg dose and the 600-mg dose was faster than with placebo (P<0.001 and P = 0.001 for the two comparisons, respectively), with median times of 1.61 hours (interquartile range, 0.78 to 7.04), 1.79 hours (1.02 to 3.79), and 6.72 hours (1.34 to >12), respectively. The time to reduction in the attack severity with the 300-mg dose and the 600-mg dose was faster than with placebo (P = 0.004 and P = 0.003), with median times of 9.27 hours (interquartile range, 1.53 to >12), 7.75 hours (2.19 to >12), and more than 12 hours (6.23 to >12). The time to complete resolution was faster with the 300-mg and 600-mg doses than with placebo (P = 0.002 and P<0.001). The percentage of attacks with complete resolution within 24 hours was 42.5% with the 300-mg dose, 49.5% with the 600-mg dose, and 27.4% with placebo. Sebetralstat and placebo had similar safety profiles; no serious adverse events related to the trial agents were reported. CONCLUSIONS: Oral sebetralstat provided faster times to the beginning of symptom relief, reduction in attack severity, and complete attack resolution than placebo. (Funded by KalVista Pharmaceuticals; KONFIDENT ClinicalTrials.gov number, NCT05259917; EudraCT number, 2021-001226-21.).
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Estudos Cross-Over , Humanos , Feminino , Método Duplo-Cego , Masculino , Adulto , Administração Oral , Pessoa de Meia-Idade , Angioedemas Hereditários/tratamento farmacológico , Adolescente , Adulto Jovem , Idoso , Angioedema Hereditário Tipos I e II/tratamento farmacológico , PirazóisRESUMO
OBJECTIVES: Antiphospholipid syndrome (APS)-associated heart valve disease (HVD) is well described. Nonetheless, limited data exist on clinical parameters associated with the course of primary APS (pAPS) patients with HVD. The goal of this study was to assess clinical features and related outcomes in patients with APS associated HVD. METHODS: In this multicentre retrospective study, we identified 33 pAPS patients with HVD (pAPS-HVD group) and compared their clinical course with 128 pAPS patients with normal heart valves on echocardiography (pAPS-control group). RESULTS: pAPS-HVD patients had more cerebrovascular events 56.3% vs 25% (p= 0.005) and livedo reticularis 24.2% vs 7.8% (p= 0.013) than pAPS-controls. Furthermore, catastrophic-APS (CAPS) (12.1% vs 2.4%, p= 0.034), recurrent thrombosis (33.3% vs 4.7%, p< 0.001), and need for advanced therapy (i.e. IVIG, plasmapheresis or rituximab) were more frequent in pAPS-HVD patients. Anti-B2GPI-IgG. [84.8% vs 63.2% (p= 0.034)], anti-cardiolipin IgG [90.9% vs. 64.8% (p= 0.005)] and triple positive aPL [75.8% vs 56.5% (p= 0.047)] were commoner in pAPS-HVD patients vs pAPS-controls. Ten of the 33 patients with pAPS-HVD underwent valve surgery which was associated with male gender, smoking, arterial limb ischaemia and livedo reticularis. CONCLUSION: pAPS-HVD patients had a more severe APS clinical course including CAPS and thrombotic events as well as with specific serology namely IgG isotype aPL antibodies and triple positivity. Our data suggest that pAPS-HVD represents a high-risk subgroup of APS patients.
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INTRODUCTION: Over 95% of healthy subjects develop anti-COVID IgG antibodies after receiving two doses of BNT162b2 COVID-19 vaccine. In comparison, 20%-30% of SLE patients do not seroconvert following 1-2 doses of COVID vaccines, potentially due to immunosuppression. The aim of this study was to assess immunogenicity and safety of BNT vaccine in SLE patients treated with Belimumab and especially the yield of a booster third dose in this population. METHODS: SLE patients treated with Belimumab in the Sheba Medical Center, Israel, were included in this study. All were recommended to receive the BNT vaccine according to national guidelines; and were advised to perform serologic tests after receiving second and third doses. Clinical data included demographics, SLE treatments, adverse effects to vaccines and SLEDAI scores performed 2 weeks before vaccinations and 6-12 weeks after receiving the second or third dose of the vaccine. RESULTS: Our cohort included 17 patients, 14 (82.35%) females, median age 50 ± 14.2 years, and disease duration 12 ± 10.57 years. Belimumab therapy was given for a mean of 6 ± 2.5 years. Of them, 15/17 patients received 3-doses of BNT vaccine. Serologic assessment was performed for 10 patients, 7/10(70%) became seropositive following the second dose, while 2/3 patients seroconverted only after the third dose. Vaccinations were well tolerated with minimal adverse events and no disease flares. SLEDAI scores before and after vaccinations were 4 ± 3.8 and 4 ± 2.7 (p = 0.69), respectively. CONCLUSIONS: Immunization with the BNT vaccine is efficacious and safe for SLE patients treated with Belimumab. Following the third dose of vaccine, immunogenicity among SLE patients mounted to 90%, thereby approximating the general healthy population. No SLE disease flares and/or significant adverse events were noted in our cohort. Assessment of seroconversion and consideration of subsequent boosters of COVID-vaccine should be considered in this group of patients.
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COVID-19 , Lúpus Eritematoso Sistêmico , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Masculino , Vacinas contra COVID-19 , Vacina BNT162 , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Resultado do Tratamento , Anticorpos AntiviraisRESUMO
BACKGROUND: While several studies have noted smell impairment in schizophrenia, it is unclear whether this impairment extends to acute psychosis and whether it is associated with more severe illness as expressed in extended hospitalization. OBJECTIVES: To evaluate the olfactory function of patients in an acute psychotic state and correlate it with clinical symptomatology and length of hospitalization. METHODS: Olfactory function was assessed in 20 patients with schizophrenia in their first week of hospital admission for acute psychosis compared with matched controls. Olfaction was evaluated via three stages: threshold, discrimination, and identification of different odors utilizing the Sniffin' Sticks test battery. RESULTS: Schizophrenia patients scored significantly lower on total smell score, discrimination, and identification abilities. A significant association was observed between hospitalization duration and total smell score and smell discrimination. No significant associations between smell and clinical symptomatology were observed. CONCLUSIONS: Study observations confirm impaired sense of smell in schizophrenia patients and suggest that smell impairment may be a potential marker of more serious illness as expressed in longer hospital stay.
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Transtornos do Olfato , Transtornos Psicóticos , Esquizofrenia , Humanos , Olfato , Esquizofrenia/complicações , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/etiologia , Transtornos Psicóticos/diagnóstico , HospitalizaçãoRESUMO
BACKGROUND & AIMS: Immune responses of solid organ transplant recipients to 2 doses of the BNT162b2 mRNA anti-SARS-CoV-2 vaccine are impaired. The immunogenicity and safety of a third dose among liver transplant (LT) recipients are unknown. This work aimed to evaluate the immune response of LT recipients to a third dose of the BNT162b2 mRNA vaccine. METHODS: Consecutive LT recipients (n = 61) in follow-up at Sheba Medical Center were included. Receptor binding domain (RBD) IgG, neutralizing antibody (NA) titers, and T-cell levels before and 21-28 days after a third vaccine dose were determined. Adverse effects after the third dose were monitored. RESULTS: The median age of LT recipients was 65 years and 57.4% were male. The humoral immune response rate improved significantly, with 56% of patients showing a response before the third vaccine dose compared to 98% after the third dose. The cellular response in 12 evaluated patients improved significantly (p = 0.008). The geometric mean of anti-RBD IgG levels, NA levels, and T-cell count also increased significantly after the third dose. NA titers after the third dose negatively correlated with age (p = 0.03), mycophenolate mofetil treatment (p = 0.005), and combined immunosuppression as opposed to calcineurin inhibitor monotherapy (p = 0.001). After the third dose, adverse effects were reported by 37% of recipients and were mostly mild (local pain and fatigue). CONCLUSION: After a third BNT162b2 mRNA vaccine, the immune response improved significantly among LT recipients, without serious adverse effects. Further studies are needed to evaluate immune response durability and to determine the optimal number and schedule of booster vaccine doses. LAY SUMMARY: The Pfizer-Biotech BNT162b2SARS-CoV-2 vaccine induced significant immunity among liver transplant recipients after a third dose. The majority of the patients developed sufficient levels of both humoral and cellular immune responses. Factors that predict non-response were older age and immunosuppressive medications.
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COVID-19 , Transplante de Fígado , Idoso , Anticorpos Antivirais , Vacina BNT162 , COVID-19/prevenção & controle , Feminino , Humanos , Imunidade Celular , Imunoglobulina G , Masculino , Transplantados , Vacinas Sintéticas , Vacinas de mRNARESUMO
BACKGROUND: Between 25% and 30% of children with peanut allergy (PA) have a relatively high-threshold peanut allergy (HTPA), with a single maximal tolerated dose (SMTD) higher than 100 mg of peanut protein (PP). However, this threshold may decrease with time, age, exercise, illness, sleep deprivation, and other covariates. OBJECTIVE: To explore the feasibility of a simplified oral immunotherapy (OIT) protocol in a group of children with HTPA. METHODS: Children with PA with an SMTD higher than 100 mg were placed on a 40-week OIT protocol of either 300 mg/d of PP or 100 mg/d for 20 weeks followed by 300 mg/d for 20 weeks. A repeat open peanut food challenge was performed after 40 weeks of treatment and at a 6-month follow-up visit. After the 40-week challenge, all children received a maintenance dosage of 2 gPP 3 times a week. RESULTS: A total of 28 children with HTPA were enrolled, with 56% boys, 89% younger than 6 years old, and a mean SMTD of 304 mg (95% confidence interval 229-378). All were placed on the described OIT protocol. Overall, 2 children were not compliant and 3 had allergic reactions at home on the dose previously tolerated in clinic, 23 completed the 40-week protocol, and all were able to consume 2 g of PP. The mean tolerated dosage at the 6-month follow-up was 8 g. This enabled most children age-appropriate dietary inclusion of peanut-containing products. CONCLUSION: In children with HTPA, a simple, fixed-dose OIT can be both safe and efficacious.
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Fabaceae , Hipersensibilidade a Amendoim , Administração Oral , Alérgenos , Arachis , Criança , Dessensibilização Imunológica/efeitos adversos , Dessensibilização Imunológica/métodos , Feminino , Humanos , Fatores Imunológicos , Masculino , Hipersensibilidade a Amendoim/terapiaRESUMO
OBJECTIVES: Infants with non-IgE-mediated food allergies are often referred to gastroenterologists or immunologists. We hypothesized that there are practice variations between these disciplines in the diagnosis and management of such infants. METHODS: A computerized questionnaire was distributed between pediatric gastroenterologists and immunologists. The questions addressed diagnosis, management, and follow-up in 3 scenarios of infants with concern for food protein-induced allergic proctocolitis (FPIAP) due to non-IgE-mediated responses to cow's milk. RESULTS: Three cases of infants with suspected FPIAP were presented: milk-based formula-fed (case 1) or breast-fed (case 2) infants that are well appearing and thriving, and a breast-fed infant who is not growing appropriately along with a personal and family history of atopy (case 3). Fifty-eight pediatric gastroenterologists and 32 immunologists completed the questionnaire. Significant differences between gastroenterologists and immunologists were noted regarding the recommended dietary changes in these scenarios. Moreover, despite available guidelines generated by both societies, most physicians confirm the diagnosis based on resolution of symptoms after the dietary change, without re-exposure to the the suspected trigger. In addition, time for recommended re-exposure in infants with FPIAP was also different; most gastroenterologists recommended waiting until 12 months of age, while immunologists suggested reintroduction earlier, up to 6 months of age. CONCLUSIONS: We identified significant practice variations in diagnosis and management of FPIAP between pediatric gastroenterologists and immunologists, with lack of adherence to society guidelines. Joint task forces of primary care pediatricians, gastroenterologists, and immunologists should provide uniform guidelines to standardize care.
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Hipersensibilidade a Leite , Alérgenos , Animais , Aleitamento Materno , Bovinos , Feminino , Humanos , Leite , Hipersensibilidade a Leite/diagnóstico , Hipersensibilidade a Leite/terapia , Proteínas do Leite/efeitos adversos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Little is known about the success of multidisciplinary thyroid eye disease (TED) clinic. OBJECTIVES: To present the characteristics, treatments, and outcomes of patients treated in a multidisciplinary TED clinic. METHODS: A medical record review of all patients who attended a TED clinic was performed. Data included demographics, medical history, laboratory tests, visual function tests, ocular examinations, clinical activity score (CAS), and assessment of quality-of-life (QOL). RESULTS: Clinic visits included 132 patients seen during 385 appointments at a TED clinic (mean 12 appointments per patient). Management of TED included medical treatments for 48 patients (36.3%) and surgical treatment for 56 (42.4%). There was a positive significant correlation between the CAS and thyroid-stimulating immunoglobulin (TSI) activity at the first visit and at the last follow-up visit (P < 0.01 and P < 0.02, respectively). However, no correlation was found between the CAS and the thyroid-stimulating hormone levels or between the free triiodothyronine (fT3) and fT4 levels at the first or last visit. There was a significant negative correlation between the CAS and color vision (-0.347, P < 0.01, Pearson correlation) at the first visit, but not between the CAS and visual acuity and visual field at either the first or last visit. Changes in the QOL and the CAS scores were significantly negatively correlated (-0.240, P < 0.01). CONCLUSIONS: Treatment and management decisions for TED should be based on multiple parameters including clinical examinations by ophthalmologists and endocrinologists, laboratory tests, and CAS and QOL scores.
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Oftalmopatia de Graves , Qualidade de Vida , Humanos , Oftalmopatia de Graves/terapia , Testes de Função Tireóidea , Acuidade VisualRESUMO
INTRODUCTION: Antiphospholipid syndrome (APS) is an autoimmune disorder manifested by thromboembolic events, recurrent spontaneous abortions and elevated titers of circulating antiphospholipid antibodies. In addition, the presence of antiphospholipid antibodies seems to confer a fivefold higher risk for stroke or transient ischemic attack. Although the major antigen of APS is ß2 glycoprotein I, it is now well established that antiphospholipid antibodies are heterogeneous and bind to various targets. Recently, antibodies to Annexin A2 (ANXA2) have been reported in APS. This is of special interest since data indicated ANXA2 as a key player in fibrinolysis. Therefore, in the present study we assessed whether anti-ANXA2 antibodies play a pathological role in thrombosis associated disease. MATERIALS AND METHODS: Mice were induced to produce anti-ANXA2 antibodies by immunization with ANXA2 (iANXA2) and control mice were immunized with adjuvant only. A middle cerebral artery occlusion stroke model was applied to the mice. The outcome of stroke severity was assessed and compared between the two groups. RESULTS: Our results indicate that antibodies to ANXA2 lead to a more severe stroke as demonstrated by a significant larger stroke infarct volume (iANXA2 133.9 ± 3.3 mm3 and control 113.7 ± 7.4 mm3; p = 0.017) and a more severe neurological outcome (iANXA2 2.2 ± 0.2, and control 1.5 ± 0.18; p = 0.03). CONCLUSIONS: This study supports the hypothesis that auto-antibodies to ANXA2 are an independent risk factor for cerebral thrombosis. Consequently, we propose screening for anti-ANXA2 antibodies should be more widely used and patients that exhibit the manifestations of APS should be closely monitored by physicians.
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Anexina A2/imunologia , Síndrome Antifosfolipídica/imunologia , Autoanticorpos/imunologia , Trombose Intracraniana/metabolismo , Adulto , Animais , Anexina A2/administração & dosagem , Anexina A2/metabolismo , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/metabolismo , Autoanticorpos/metabolismo , Autoimunidade/imunologia , Modelos Animais de Doenças , Feminino , Fibrinólise/imunologia , Humanos , Infarto da Artéria Cerebral Média/imunologia , Infarto da Artéria Cerebral Média/fisiopatologia , Injeções Subcutâneas , Trombose Intracraniana/etiologia , Ataque Isquêmico Transitório/imunologia , Camundongos , Camundongos Endogâmicos BALB C/imunologia , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/imunologia , beta 2-Glicoproteína I/metabolismoRESUMO
OBJECTIVES: The clinical manifestations of the antiphospholipid syndrome (APS) are heterogeneous and related to anti-phospholipid antibodies (aPL). There is some evidence that B cells are involved in the pathogenesis of this condition. Thus the ability of rituximab (RTX) to deplete B cells makes it an appealing potential therapy for refractory antiphospholipid syndrome (APS). Real world data on RTX treatment of APS are still lacking. This study was conducted to report outcomes of RTX administration in the treatment of different aspects of APS. METHODS: This is a retrospective case series study on APS patients from 3 medical centres in Israel who were treated with RTX during 2010-2019 for refractory manifestations of APS including diffuse alveolar haemorrhage, recurrent thrombosis, cytopenia, neurological and skin manifestations. Medical records were reviewed regarding the clinical indication for RTX treatment, concomitant medications, RTX protocol, aPL status and response to treatment. Outcomes were defined as complete response if full resolution of the "indicated manifestation" was achieved and maintained for at least 12 months, partial response or no response. RESULTS: We identified 40 APS patients who were treated with RTX for refractory manifestations of this condition, of whom, 24 patients (60%) were female with a mean age of 40 years, and 31 patients (78%) were diagnosed with primary APS. A favourable response to RTX was documented in 32 patients (80%) including a complete response in 22 patients (55%). Response to RTX treatment was associated with a rituximab protocol of 375mg/m2 x 4 compared to a fixed dose of 1000 mg x2 (100% vs. 65%; p=0.01). Complete response was associated with a decrease in aPL titres within 4-6 months post treatment, whereas no significant change in aPL titres was observed in patients with partial or no response. CONCLUSIONS: Consistent with previous small case series, we report a good therapeutic response to RTX in patients with difficult to treat manifestations of APS. In this cohort, treatment protocols were associated with outcomes. Although further studies are required to verify our observations, our data support a plausible role for B cell depletion in refractory APS.
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Síndrome Antifosfolipídica , Trombocitopenia , Adulto , Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/tratamento farmacológico , Feminino , Humanos , Estudos Retrospectivos , Rituximab/uso terapêuticoRESUMO
BACKGROUND: Changes in the quality of life (QOL) of patients with thyroid eye disease (TED) were examined during a 3-year follow-up in a multidisciplinary eye clinic, and factors that may improve QOL were identified. METHODS: A retrospective review of medical records of all patients who attended the TED clinic at Sheba Medical Center, Israel, from May 2016 to May 2019 was performed. The retrieved data included demographics, comprehensive ophthalmic examination findings, clinical activity scores (CAS), laboratory test results, and QOL assessments by the Graves' Orbitopathy QOL (GO-QOL) questionnaire. RESULTS: One hundred thirty-two TED clinic patients were examined. Thirty patients (22.72%) received medical treatment consisting of steroids according to the European Group on Graves' Orbitopathy (EUGOGO) protocol, high-dose steroids, or immunosuppressive drugs. Twenty-eight patients (21.21%) underwent surgical rehabilitation (decompression, strabismus, or eyelid surgery). There was a significant increase in total QOL score after steroid treatment according to the EUGOGO protocol, after decompression surgery, and after strabismus surgery compared to pre-treatment total QOL (p=0.04, p=0.021, and p=0.042, respectively, matched pairs). In addition, there were significant positive correlations between the changes in the total QOL score and the change in thyroid-stimulating immunoglobulin (TSI) as well as the change in CAS among the patients who underwent medical and surgical interventions. CONCLUSIONS: QOL improved significantly after medical/surgical treatments. A change in the CAS and in the TSI may also correlate with change in QOL. Periodic evaluation of TED patients' QOL is recommended for enhanced and more comprehensive management.
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Oftalmopatia de Graves , Qualidade de Vida , Seguimentos , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/terapia , Humanos , Israel/epidemiologia , Estudos RetrospectivosRESUMO
To update the European League Against Rheumatism (EULAR) recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) published in 2011. Four systematic literature reviews were performed regarding the incidence/prevalence of vaccine-preventable infections among patients with AIIRD; efficacy, immunogenicity and safety of vaccines; effect of anti-rheumatic drugs on the response to vaccines; effect of vaccination of household of AIIRDs patients. Subsequently, recommendations were formulated based on the evidence and expert opinion. The updated recommendations comprise six overarching principles and nine recommendations. The former address the need for an annual vaccination status assessment, shared decision-making and timing of vaccination, favouring vaccination during quiescent disease, preferably prior to the initiation of immunosuppression. Non-live vaccines can be safely provided to AIIRD patients regardless of underlying therapy, whereas live-attenuated vaccines may be considered with caution. Influenza and pneumococcal vaccination should be strongly considered for the majority of patients with AIIRD. Tetanus toxoid and human papilloma virus vaccination should be provided to AIIRD patients as recommended for the general population. Hepatitis A, hepatitis B and herpes zoster vaccination should be administered to AIIRD patients at risk. Immunocompetent household members of patients with AIIRD should receive vaccines according to national guidelines, except for the oral poliomyelitis vaccine. Live-attenuated vaccines should be avoided during the first 6 months of life in newborns of mothers treated with biologics during the second half of pregnancy. These 2019 EULAR recommendations provide an up-to-date guidance on the management of vaccinations in patients with AIIRD.
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Antirreumáticos/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Infecções Bacterianas/prevenção & controle , Doenças Reumáticas/tratamento farmacológico , Vacinas/uso terapêutico , Viroses/prevenção & controle , Características da Família , Hepatite A/prevenção & controle , Vacinas contra Hepatite A/uso terapêutico , Hepatite B/prevenção & controle , Vacinas contra Hepatite B/uso terapêutico , Herpes Zoster/prevenção & controle , Vacina contra Herpes Zoster/uso terapêutico , Humanos , Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/uso terapêutico , Tétano/prevenção & controle , Toxoide Tetânico/uso terapêutico , Vacinas Atenuadas/uso terapêuticoRESUMO
INTRODUCTION: Small-fiber neuropathy is rare in children. It has been associated with several autoimmune disorders, but there are no reports of an autoinflammatory etiology. METHODS: The data of four children/adolescents presenting with erythromelalgia and neuropathic pain from 2014 to 2019 were collected retrospectively from the electronic database of a pediatric medical center. RESULTS: Results of clinical and/or electrophysiological evaluation excluded large nerve fiber involvement. Skin biopsy results confirmed small-fiber neuropathy. According to genetic analysis, two patients were heterozygous and one was homozygous for mutations in the familial Mediterranean fever (MEFV) gene. Behcet disease was diagnosed in the fourth patient. Treatment with anti-interleukin-1 agents, intravenous immunoglobulin, and glucocorticoids was beneficial. DISCUSSION: The diagnosis of small-fiber neuropathy should be considered in children/adolescents presenting with erythromelalgia. A thorough investigation is required to reveal the underlying disorder. Clinicians should be alert to the peripheral neurological manifestations of autoinflammatory syndromes because effective treatments are available.
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Eritromelalgia/complicações , Eritromelalgia/diagnóstico , Neuropatia de Pequenas Fibras/complicações , Neuropatia de Pequenas Fibras/diagnóstico , Adolescente , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/fisiopatologia , Criança , Eritromelalgia/fisiopatologia , Feminino , Humanos , Inflamação/complicações , Inflamação/diagnóstico , Inflamação/fisiopatologia , Estudos Retrospectivos , Neuropatia de Pequenas Fibras/fisiopatologia , SíndromeRESUMO
BACKGROUND: Chronic urticaria is defined by the presence of itchy wheals, sometimes accompanied by angioedema, lasting for at least 6 weeks. In children, most cases occur without an eliciting factor and are defined as chronic spontaneous urticaria (CSU). CSU affects up to 0.75% of children with a negative impact on quality of life and school performance. CSU is treated in adults with second-generation antihistamines, increased up to four times normal doses for second-line treatment. Omalizumab (a monoclonal antibody to IgE) may be recommended as third-line therapy. A similar protocol is used in children, yet little is known of its efficacy and safety. OBJECTIVES: To summarize our multi-center experience in treating children with recalcitrant CSU with omalizumab. METHODS: A retrospective multi-center case series conducted in 5 tertiary care centers in Israel. Patients included were children <18 years old diagnosed with recalcitrant CSU who were treated with omalizumab. Patients were followed up throughout the duration of omalizumab therapy/symptom remission. Patients' electronic medical records were used to gather data. RESULTS: Nineteen participants (11 F; 8 M) presented with CSU between ages 6 and 16.9 years. Sixteen (84%) responded to omalizumab, including children <12 years old, although two became non-responsive after 6-12 months of therapy. Another three patients (16%) were resistant to treatment, achieving remission through fourth-line (Cyclosporine A) or other therapies. CONCLUSION: Children with recalcitrant CSU, even those <12 years old, respond well to standard-dose, third-line omalizumab therapy at rates similar to adults. Yet, some cases may become non-responsive with ongoing treatment.
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Antialérgicos , Urticária Crônica , Urticária , Adolescente , Adulto , Antialérgicos/uso terapêutico , Criança , Doença Crônica , Humanos , Israel , Omalizumab/uso terapêutico , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento , Urticária/tratamento farmacológicoRESUMO
Innate immunity is one of two immune defence system arms. It is present at birth and does not require 'learning' through exposure to foreign organisms. It activates various mechanisms collectively to eliminate pathogens and hold an infection until the adaptive response are mounted. The innate immune system consists of four elements: the epithelial barrier, cells (e.g. macrophages, NK cells), plasma proteins (e.g. complement) and cytokines. These components act in concert to induce complex processes, as well as recruitment, activation and differentiation of adaptive responses. The innate response is more than just the 'first line of defence', as it essentially withholds the vast majority of any intruder, has a complex interplay with the adaptive arm and is crucial for survival of the host. Finally, yet importantly, a myriad of diseases has been linked with innate immune dysregulation. In this mini-review we will shed some light on these conditions, particularly regarding autoinflammatory ones.
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Doenças do Sistema Imunitário/fisiopatologia , Imunidade Celular/fisiologia , Imunidade Inata/fisiologia , Células Matadoras Naturais/imunologia , Animais , Citocinas/metabolismo , Feminino , Doenças Hereditárias Autoinflamatórias/fisiopatologia , Humanos , Doenças do Sistema Imunitário/epidemiologia , Incidência , Masculino , Avaliação das Necessidades , Fatores de RiscoRESUMO
BACKGROUND: Most children with egg allergy (EA) can tolerate extensively heated and baked egg (EHBE). Consumption of EHBE may promote faster resolution of EA; however, no consensus exists as to the required amounts and treatment protocols. OBJECTIVE: To evaluate the efficacy and safety of a structured graduated exposure protocol (SGEP) with EHBE in promoting tolerance to eggs in EA children under 2 years of age. METHODS: In a case-control study, EA children aged < 2 years who were treated with SGEP including EHBE were compared to children treated with strict avoidance. Data were collected from records and telephone questionnaires. Analysis was performed using non-parametric Kaplan-Meier and Cox proportional hazard regression models. RESULTS: Thirty-nine egg-allergic children with a median age at intervention of 16 months (interquartile range: 13-19) were treated with SGEP and followed to a median age of 39 months (26.8-50.0). The median age at resolution of EA was compared to a matched group of 80 children treated with strict avoidance at least until 2 years of age or earlier natural resolution and followed to a median age of 69 months (46-104). The median estimated age at EA resolution in the SGEP group was 24 months (95% CI, 19.5-28.5 months), compared to 78 months (95% CI, 53-102) in the control group, P < .001. At last follow-up, 82% of treated children were tolerant to lightly cooked eggs vs 54% of controls, P = .001. CONCLUSION: A structured protocol with EHBE appears to promote faster resolution of EA.
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Dessensibilização Imunológica/métodos , Hipersensibilidade a Ovo/terapia , Alérgenos/imunologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Hipersensibilidade a Ovo/imunologia , Ovos , Feminino , Seguimentos , Temperatura Alta , Humanos , Tolerância Imunológica , Imunoglobulina E/metabolismo , Masculino , Desnaturação ProteicaRESUMO
BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, distinct pulmonary vascular disease, which is caused by chronic obstruction of major pulmonary arteries. CTEPH can be cured by pulmonary endarterectomy (PEA). PEA for CTEPH is a challenging procedure, and patient selection and the perioperative management are complex, requiring significant experience. OBJECTIVES: To describe the establishment of a national CTEPH-PEA center in Israel and present results of surgery. METHODS: In this study, we reviewed the outcomes of PEA in a national referral, multi-disciplinary center for CTEPH-PEA. The center was established by collaborating with a high-volume center in Europe. A multidisciplinary team from our hospital (pulmonary hypertension specialist, cardiac surgeon, cardiac anesthesiologist and cardiac surgery intensivist was trained under the guidance of an experienced team from the European center. RESULTS: A total of 38 PEA procedures were performed between 2008 and 2018. We included 28 cases in this analysis for which long-term follow-up data were available. There were two hospital deaths (7%). At follow-up, median New York Heart Association (NYHA) class improved from III to I (P < 0.0001), median systolic pulmonary pressure decreased from 64 mmHg to 26 mmHg (P < 0.0001), and significant improvements were seen in right ventricular function and exercise capacity. CONCLUSIONS: A national center for performance of a rare and complex surgical procedure can be successfully established by collaboration with a high-volume center and by training a dedicated multidisciplinary team.
Assuntos
Endarterectomia/métodos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/cirurgia , Embolia Pulmonar/complicações , Embolia Pulmonar/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/cirurgia , Encaminhamento e Consulta , Fatores de Risco , Resultado do Tratamento , Adulto JovemAssuntos
Eosinofilia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Eosinofilia/diagnóstico , Adulto , Vasculite/diagnóstico , IdosoRESUMO
OBJECTIVE: To evaluate the efficacy and safety of a structured gradual exposure protocol (SGEP) with extensively heated and baked milk in promoting allergy resolution in children with cow milk allergy (CMA). STUDY DESIGN: In a case control study, children with CMA aged 1-4 years who were treated with SGEP including extensively heated and baked milk, were compared with children treated with strict avoidance. Data were collected from medical records and from validated telephone questionnaires. Data analysis was performed using a nonparametric Kaplan-Meier and proportional hazard Cox regression model, after evaluation of the adequacy of the case control matching. RESULTS: There were 43 children with milk allergy-26 (62%) males with a mean age at intervention of 21 months (range, 12-47 months)-who were treated with SGEP and followed to a mean age of 40 months (range, 20-82 months). The median age at resolution of CMA was compared with a matched group of 67 children treated with strict avoidance at least until 4 years of age or followed until earlier resolution, with a mean age at follow-up of 71 months (range, 11-176 months). The median estimated age at CMA resolution in the SGEP group was 36 months (95% CI, 34.5-49.7) compared with 98 months (95% CI, 82.4-114.1) in controls (P < .001). At last follow-up, 86% of treated children were tolerant to unheated milk proteins vs 52% of controls (P = .003). CONCLUSION: A structured protocol with extensively heated and baked milk seems to promote faster resolution of CMA.
Assuntos
Temperatura Alta , Imunização/métodos , Hipersensibilidade a Leite/diagnóstico , Hipersensibilidade a Leite/terapia , Leite/imunologia , Adaptação Fisiológica/imunologia , Fatores Etários , Animais , Estudos de Casos e Controles , Pré-Escolar , Feminino , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Proteínas do Leite/imunologia , Prognóstico , Modelos de Riscos Proporcionais , Índice de Gravidade de Doença , Fatores Sexuais , Testes Cutâneos , Fatores de TempoRESUMO
Each person expresses a potentially unique subset of â¼ 400 different olfactory receptor subtypes. Given that the receptors we express partially determine the odors we smell, it follows that each person may have a unique nose; to capture this, we devised a sensitive test of olfactory perception we termed the "olfactory fingerprint." Olfactory fingerprints relied on matrices of perceived odorant similarity derived from descriptors applied to the odorants. We initially fingerprinted 89 individuals using 28 odors and 54 descriptors. We found that each person had a unique olfactory fingerprint (P < 10(-10)), which was odor specific but descriptor independent. We could identify individuals from this pool using randomly selected sets of 7 odors and 11 descriptors alone. Extrapolating from this data, we determined that using 34 odors and 35 descriptors we could individually identify each of the 7 billion people on earth. Olfactory perception, however, fluctuates over time, calling into question our proposed perceptual readout of presumably stable genetic makeup. To test whether fingerprints remain informative despite this temporal fluctuation, building on the linkage between olfactory receptors and HLA, we hypothesized that olfactory perception may relate to HLA. We obtained olfactory fingerprints and HLA typing for 130 individuals, and found that olfactory fingerprint matching using only four odorants was significantly related to HLA matching (P < 10(-4)), such that olfactory fingerprints can save 32% of HLA tests in a population screen (P < 10(-6)). In conclusion, a precise measure of olfactory perception reveals meaningful nonolfactory genetic information.