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INTRODUCTION: The PAGANINI study evaluated the efficacy and safety of the selective P2X3 antagonist eliapixant in patients with refractory chronic cough (RCC). METHODS: PAGANINI was a randomized, double-blind, parallel-group, placebo-controlled, multicenter, dose-finding, phase 2b study. Adults with RCC lasting ≥ 12 months and cough severity ≥ 40 mm on a visual analog scale at screening were enrolled. Participants were randomized 1:1:1:1 to twice-daily 25 mg, 75 mg, or 150 mg oral eliapixant or placebo for 12 weeks. The primary endpoint was change from baseline in 24-h cough count after 12 weeks of intervention. RESULTS: Overall, 310 participants were randomized to twice-daily eliapixant 25 mg (n = 75), 75 mg (n = 78), 150 mg (n = 80), or placebo (n = 77). A statistically significant dose-response signal with eliapixant was detected for the primary endpoint (all dose-response models, adjusted p < 0.1; one-sided). Adverse events (AEs) were reported in 39 (51%) participants with placebo and 43-51 (57-65%) participants receiving eliapixant. The most common AE was dysgeusia, occurring in 1% (n = 1) of the placebo group and 1-16% (n = 1-13) of the eliapixant groups in a dose-related manner. One case of a moderate drug-induced liver injury occurred in a participant receiving 150 mg twice-daily eliapixant. CONCLUSION: Eliapixant demonstrated efficacy and a favorable taste tolerability profile in RCC. However, a drug-induced liver injury contributed to intensified liver monitoring in clinical trials with eliapixant and discontinuation of the entire development program in all indications by Bayer AG. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04562155; registered September 18, 2020.
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Carcinoma de Células Renais , Neoplasias Renais , Adulto , Humanos , Tosse/tratamento farmacológico , Método Duplo-Cego , Resultado do TratamentoRESUMO
Chronic sclerosing sialadenitis may represent one of many manifestations of an immunoglobulin G4-related disease. However, existing studies typically consist of small patient cohorts rarely conducted in Western populations. The clinical behavior of chronic sclerosing sialadenitis, including follow-up data, warrants further study. Thus, we aimed to determine whether chronic sclerosing sialadenitis always presents as IgG4-related disease or associates with autoimmune diseases and to determine which additional examinations patients may require. Between 2000 and 2017, 51 patients undergoing submandibular gland resection within the Helsinki University Hospital area were diagnosed with chronic sclerosing sialadenitis. We re-evaluated all specimens and performed immunostaining for IgG4. IgG and CD31 stainings were performed for IgG4-positive specimens. IgG4-related disease diagnosis was defined by the Boston consensus statement criteria. We revised clinical data, distributing a follow-up questionnaire to patients to register symptoms of IgG4-related disease or autoimmune disease during follow-up. The chronic sclerosing sialadenitis criteria were fulfilled in 34 patients, whereby 17 were diagnosed as non-sclerosing chronic sialadenitis. In 19 cases, a sialolith associated with a salivary gland lesion. In total, 12 of 51 cases were recognized as IgG4-positive, while two met the criteria for IgG4-related disease. These two cases belonged to the non-sclerosing chronic sialadenitis group, and both involved other organs. The histopathological features between chronic sclerosing sialadenitis and non-sclerosing chronic sialadenitis overlapped regarding the degree of fibrosis and inflammatory infiltrates. In the Finnish population, chronic sclerosing sialadenitis of the submandibular gland does not appear to present as IgG4-related disease. Non-sclerosing chronic sialadenitis can associate with IgG4-related disease. A histopathological distinction between chronic sclerosing sialadenitis and non-sclerosing chronic sialadenitis is not always unequivocal and the presence of a sialolith does not exclude IgG4-positivity. Therefore, immunostaining for IgG4 should be performed when dense plasma cell infiltration is present in either non-sclerosing chronic sialadenitis or chronic sclerosing sialadenitis.
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Autoimunidade , Doença Relacionada a Imunoglobulina G4/imunologia , Imunoglobulina G/análise , Sialadenite/imunologia , Doenças da Glândula Submandibular/imunologia , Glândula Submandibular/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Finlândia , Humanos , Doença Relacionada a Imunoglobulina G4/patologia , Doença Relacionada a Imunoglobulina G4/cirurgia , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Esclerose , Sialadenite/patologia , Sialadenite/cirurgia , Glândula Submandibular/patologia , Glândula Submandibular/cirurgia , Doenças da Glândula Submandibular/patologia , Doenças da Glândula Submandibular/cirurgiaRESUMO
Acute otitis media (AOM) commonly causes pain and distress in children. Existing analgesic ototopical drops have limited effectiveness due to the impermeable nature of the tympanic membrane. We developed a local drug delivery system to provide sustained pain relief in patients with AOM, achieved by applying a single dose of a hydrogel formulation onto the tympanic membrane. Successful drug delivery across intact tympanic membranes was demonstrated using the amino-amide anesthetic, bupivacaine, and a highly potent site 1 sodium channel blocker anesthetic, tetrodotoxin. The chemical permeation enhancers incorporated in the delivery system increased the permeability of the tympanic membrane to the anesthetics considerably. The drug levels measured using a previously developed ex vivo model reflect the potential for highly effective local anesthesia.
Assuntos
Anestésicos Locais/administração & dosagem , Bupivacaína/administração & dosagem , Sistemas de Liberação de Medicamentos , Otite Média/complicações , Dor/tratamento farmacológico , Tetrodotoxina/administração & dosagem , Doença Aguda , Humanos , Dor/etiologiaRESUMO
PURPOSE: To analyse costs related to the diagnosis and treatment of patients with sialolithiasis and sialadenitis managed with sialendoscopy, and to prospectively evaluate the impact of sialendoscopy on health-related quality of life (HRQoL) in a longitudinal follow-up study. METHODS: All patients undergoing sialendoscopy or sialendoscopy-assisted surgery at a tertiary care university hospital between January 2014 and May 2016 were identified from a surgical database, and the direct hospital costs were retrospectively evaluated from 1 year before to 1 year after the sialendoscopy. The 15D HRQoL questionnaire and a questionnaire exploring the use of health care services during the preceding 3 months were mailed to the patients before sialendoscopy as well as at 3 and 12 months after the operation. RESULTS: A total of 260 patients were identified. Mean total hospital costs, costs related to the sialendoscopy, and complications were significantly higher in sialolithiasis patients than in patients with other diagnoses. 74 patients returned the baseline 15D questionnaire, and 51 patients all three 15D questionnaires. At baseline, the dimensions "discomfort and symptoms" and "distress" were lower in patients than in age- and gender-standardised general population, but the total 15D score did not differ significantly. The dimension "discomfort and symptoms" improved significantly at 3 and 12 months postoperatively, and the mean total HRQoL score improved in patients with sialolithiasis at 3 months postoperatively. CONCLUSIONS: The costs related to sialendoscopy are substantial and the cost-effectiveness of sialendoscopy warrants further studies. However, sialendoscopy seems to reduce patients' discomfort and ailments and to improve HRQoL at least in patients with sialolithiasis.
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Análise Custo-Benefício , Endoscopia/economia , Custos Hospitalares/estatística & dados numéricos , Qualidade de Vida , Cálculos das Glândulas Salivares/cirurgia , Sialadenite/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Endoscopia/métodos , Feminino , Finlândia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Cálculos das Glândulas Salivares/economia , Sialadenite/economia , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: To assess the susceptibility of salivary stones to bacterial biofilm formation, which may be involved in the development of salivary gland infection, and to investigate a relation between microbiological aspects and patient characteristics. METHODS: This prospective study comprises of 54 patients with sialolithiasis attended in Helsinki University Hospital during 2014-2016. A total of 55 salivary stones were removed, and studied for biofilm formation using fluorescence microscopy and sonication. The isolated organisms were quantified and identified using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. RESULTS: Biofilm formation was confirmed on the surface of 39 (70.9%) stones. A total of 96 microorganisms were isolated from 45 salivary stones (81.8%). Two or more organisms were isolated in 33 (73.3%) cases. The main isolates were Streptococcus mitis/oralis (n = 27; 28.1%), followed by Streptococcus anginosus (n = 10; 9.6%), Rothia spp. (n = 8; 8.3%), Streptococcus constellatus (n = 7; 7.3%), and Streptococcus gordonii (n = 6; 6.2%). In all patients showing pre-operative (12 cases) or peri-operative (three cases) drainage of pus, the presence of biofilm was detected in microscopy (p = 0.004). Four patients showed post-operative infection, and in three of them (75.0%), the presence of biofilm was detected. Increased number of pus drainage was found among patients with reflux symptoms or use of proton-pump inhibitors. CONCLUSIONS: Salivary stones are susceptible to bacterial biofilm formation, which could be related with the development and severity of the inflammation and the refractory nature of the disease. Sonication of salivary gland stones could be a useful method for finding the etiology of the chronic infection.
Assuntos
Biofilmes , Endoscopia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Cálculos das Glândulas Salivares/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Cálculos das Glândulas Salivares/complicações , Cálculos das Glândulas Salivares/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: The aim of this prospective study was to evaluate the efficacy of sialendoscopy in the management of adult chronic recurrent parotitis without sialolithiasis. In addition, preliminary results of an initial randomized placebo-controlled trial of single-dose intraductal steroid injection given concurrently with sialendoscopy, are presented. METHODS: Forty-nine adult patients with chronic recurrent parotitis without sialoliths were included in this study. They underwent sialendoscopy and were randomized to receive either a concurrent intraductal injection of isotonic saline solution or 125 mg of hydrocortisone. Symptom severity was evaluated with visual analogue scale (VAS) and by recording symptom frequency and course with a multiple-choice questionnaire completed preoperatively and at 3, 6, and 12 months after the procedure. RESULTS: The mean VAS score was 5.6 preoperatively and dropped to 2.9 at 3 months, 3.0 at 6 months, and 2.7 at 12 months after the procedure. The VAS score and the frequency of symptoms were significantly lower at 3 (p < 0.001), 6 (p < 0.001) and 12 (p < 0.001) months after the procedure when compared with the preoperative scores indicating that sialendoscopy reduces the symptoms of recurrent parotitis. However, complete permanent resolution of symptoms was rare. Single-dose steroid injection concomitant to sialendoscopy provided no additional benefit, but the current study is not sufficiently powered to determine a clinical difference between the steroid and non-steroid groups. CONLUSION: Sialendoscopy appears to reduce the symptoms of chronic recurrent parotitis. While total permanent symptom remission is rare, sialendoscopy can be considered a safe and relatively efficacious treatment method for this patient group.
Assuntos
Anti-Inflamatórios/uso terapêutico , Endoscopia/métodos , Hidrocortisona/uso terapêutico , Parotidite/terapia , Adulto , Idoso , Doença Crônica , Terapia Combinada , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Parotidite/diagnóstico , Estudos Prospectivos , Cálculos das Glândulas Salivares , Resultado do TratamentoRESUMO
Background: Aspergillus can cause fungal rhinosinusitis (FRS). We aimed to identify risk factors for sinonasal Aspergillus disease. Methods: Patients with a positive sinonasal mycological culture for Aspergillus species diagnosed in our hospital located in a continental climate were included in the 9-year retrospective study. Results: Of the 86 patients, 3 had invasive FRS (IFRS), 51 had fungal ball (FB) disease, and 32 had chronic rhinosinusitis with fungus (CFRS). In the IFRS group, all patients had a malignancy and were immunocompromised. Allergies, allergic rhinitis, asthma, nasal polyps, and the use of inhaled and nasal steroids were more common in the CFRS group, and IgE levels were greater than those in the FB and IRFS groups (p < 0.05). Conclusion: FB disease is a relatively symptom-free single-sinus disease among elderly individuals, and IFRS is dominant among immunocompromised patients. We discovered a third patient group, predominantly with nasal polyps, atopy, asthma, and elevated blood IgE and eosinophils, that did not fulfill the allergic FRS (AFRS) criteria. It is possible that a less fulminant category of underdiagnosed AFRS exists in cold climates. Treatment with local debridement is usually sufficient for FRS, apart from IFRS, and relapses are not common in cold climates.
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OBJECTIVE: To measure the inflammatory cytokines of middle ear effusion (MEE) in otitis media (OM) associated with asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) with or without nonsteroidal anti-inflammatory drug (NSAID) sensitivity to strengthen our assumption that OM is part of the same inflammatory entity. The potential individual differences between MEE inflammatory cytokines could be used in clinical practice for more individual characterization of the inflammation. STUDY DESIGN: Case-control study. SETTING: Tertiary referral center. PATIENTS: Convenience sample of 24 case patients with otitis media with effusion (OME) or chronic otitis media (COM), asthma, and CRSwNP, 14 of whom had NSAID intolerance, and 8 controls with OME but no history of asthma, CRSwNP, or NSAID intolerance. INTERVENTION: Diagnostic. MAIN OUTCOME AND MEASURE: Inflammatory cytokines including interleukins (IL)-4, IL-5, IL-6, IL-13, and interferon gamma (IFN-γ) in middle ear effusion. RESULTS: The MEE mass fractions of IL-5 ( p = 0.003) and IFN-γ ( p = 0.048) were higher among our case patients with OME/COM than among the controls. For IL-4 and IL-13, the mass fractions were also higher among the case patients than the controls, but this difference was not statistically significant ( p = 0.199 and p = 0.617, respectively). We found no difference between the IL-6 mass fractions of the groups. We found notable heterogeneity in individual patients' cytokine levels. CONCLUSIONS: According to our findings, OM, when present, should be considered part of the respiratory inflammatory process associated with asthma and CRSwNP. The individual differences in MEE cytokine levels could be useful as biomarkers.
Assuntos
Anti-Inflamatórios não Esteroides , Asma , Citocinas , Pólipos Nasais , Otite Média com Derrame , Rinite , Sinusite , Humanos , Pólipos Nasais/complicações , Pólipos Nasais/imunologia , Sinusite/complicações , Feminino , Masculino , Citocinas/metabolismo , Asma/complicações , Adulto , Pessoa de Meia-Idade , Estudos de Casos e Controles , Anti-Inflamatórios não Esteroides/efeitos adversos , Rinite/complicações , Doença Crônica , Otite Média com Derrame/complicações , Interferon gama , Interleucina-5 , Interleucina-4 , Interleucina-6 , Interleucina-13 , Idoso , RinossinusiteRESUMO
AIM: To characterize the features of juvenile parotitis in a prospective setup and epidemiology. METHODS: All children with parotitis admitted to Helsinki University Central Hospital 2005-2010 were recruited. Clinical characteristics, given treatment, outcome, blood leukocyte count, C-reactive protein, serum amylase and trypsinogen, SPINK-1 genotype and mumps antibodies were recorded. To map the epidemiology, a questionnaire was sent to 1000 randomly selected 13-year-old children. RESULTS: The prospective study included 41 children (aged ≤ 17) with acute parotitis, all in good general condition. Serum amylase, but not trypsinogen, was elevated in majority of the cases (79%) and C-reactive protein in 68%. Eleven (27%) children had an elevated blood leukocyte count. None had acute mumps. Most children recovered well, 51% being treated symptomatically only. Seven children were treated on ward. Seventeen (46%) children had recurrent symptoms. One child (2.4%) had SPINK P55S mutation. According to the epidemiological questionnaire, 1.1% of the respondents (8/728, response rate 73%) reported a verified episode(s) of parotitis. CONCLUSION: Juvenile parotitis has a frequency close to 1%. In the majority, the general condition is good during the episode. Serum amylase serves as an additional marker for the disease. Parotitis has a tendency to recur in almost half of the cases.
Assuntos
Parotidite , Doença Aguda , Adolescente , Amilases/sangue , Anticorpos Antivirais/sangue , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Finlândia/epidemiologia , Seguimentos , Inquéritos Epidemiológicos , Humanos , Contagem de Leucócitos , Masculino , Vírus da Caxumba/imunologia , Parotidite/sangue , Parotidite/diagnóstico , Parotidite/epidemiologia , Parotidite/terapia , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) has been considered an acquired condition. Positive first-degree family history has been reported in 1% of cases. The geographic and genetic isolation of the Finnish population offers exceptional opportunities for inheritance studies. In this questionnaire study, we explored the familial aggregation of N-ERD in 66 Finnish families of patients with N-ERD. The majority of patients (67%) had a positive family history of NSAID intolerance, asthma, nasal polyposis, or N-ERD. Furthermore, 55% had a positive first-degree family history of asthma, 21% nasal polyposis, 20% NSAID intolerance, and 11% N-ERD. The prevalence of asthma, nasal polyposis, NSAID intolerance, and N-ERD among first-degree relatives was 13%, 5%, 4%, and 2%, respectively. We present the pedigrees of the 44 affected families. According to our findings, Finnish patients with N-ERD seem to have a genetic susceptibility to it.
Assuntos
Asma Induzida por Aspirina , Asma , Pólipos Nasais , Sinusite , Humanos , Aspirina , Sinusite/cirurgia , Anti-Inflamatórios não Esteroides/efeitos adversos , Asma/epidemiologia , Pólipos Nasais/induzido quimicamente , Pólipos Nasais/genética , Pólipos Nasais/epidemiologia , Asma Induzida por Aspirina/epidemiologia , Asma Induzida por Aspirina/genéticaRESUMO
BACKGROUND: The aetiology of idiopathic facial nerve palsy (Bell's palsy, BP) and sudden sensorineural hearing loss (SSNHL) are not known. It has been proposed that common respiratory tract viruses play a part in the pathophysiology of these diseases. OBJECTIVES: The incidence of many infectious diseases decreased during the lockdown of the society that took place during the COVID-19 pandemic. We investigated a possible change in the incidence of BP and SSNHL during the lock-down. MATERIAL AND METHODS: We searched the patient records for all BP and SSNHL cases between 1 Jan 2017 - 31 Aug 2020 at the hospital district of Helsinki and Uusimaa that covers a population of about 1.2 million. RESULTS: The mean monthly incidence on BP decreased during the COVID-19 pandemic lock-down. No change in the SSNHL incidence was discovered. CONCLUSIONS AND SIGNIFICANCE: There is reason to speculate that one aetiologic reason for BP are transmittable respiratory tract pathogens.
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Paralisia de Bell , COVID-19 , Perda Auditiva Neurossensorial , Paralisia de Bell/epidemiologia , Paralisia de Bell/etiologia , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Perda Auditiva Neurossensorial/complicações , Perda Auditiva Neurossensorial/etiologia , Humanos , Incidência , Pandemias , Distanciamento FísicoRESUMO
Non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) is an adult-onset inflammatory condition of the upper and lower airways. It is characterized by the co-existence of asthma, nasal polyposis, and hypersensitivity to NSAIDs. Over one-fourth of patients also have symptoms of chronic middle-ear infection. The clinical course of NERD is often severe and generally requires multimodal treatment with recurrent surgical measures. Studies presenting the disease burden and subjective symptom control of NERD are limited. In this qualitative questionnaire study, we present the clinical characteristics of asthma, nasal polyposis, NSAID intolerance and possible recurrent or chronic middle-ear infection of 66 confirmed NERD patients treated at our tertiary referral center between January 2016 and May 2017. Additionally, we present the patient-reported disease control of asthma, nasal polyposis, and middle-ear symptoms on a four-category Likert scale. The proportion of NERD patients with recurrent or chronic middle-ear infection was 18%. The proportion of good or very good subjective disease control was 83% for asthma, 58% for nasal polyposis, and 33% for chronic middle-ear infection, if present. Chronic middle-ear infection is common among NERD patients and should more often be recognized as part of the entity. Together with nasal polyposis, chronic middle-ear infection seems to affect patients more than asthma. The patient's perspective of disease control should be considered when planning the interdisciplinary follow-up and treatment of NERD.
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PURPOSE: An important outcome measure of patient care is the impact on the patient's health-related quality of life (HRQoL). Current ear-specific HRQoL instruments are designed for one diagnosis and emphasize different subdivisions such as symptoms, hearing problems, psychosocial impact, and the need for care. The optimal length of the recall period has not been studied. For these reasons, a new survey is needed that would cover most chronic ear diseases. METHODS: A preliminary 24-item survey (EOS-24) was created. Untreated adult patients (included n = 186) with one of seven different chronic otologic conditions from all university hospitals in Finland were recruited to respond to EOS-24 and the 15D general HRQoL instrument. The recruiting otologists evaluated the severity of the disease and the disability caused by it. A control group was recruited. Based on the patients' responses in different diagnosis groups, the items were reduced according to pre-defined criteria. The resulting survey was validated using a thorough statistical analysis. RESULTS: The relevance and necessity of the original 24 items were thoroughly investigated, leading to the exclusion of 8 items and the modification of 1. The remaining 16 items were well-balanced between subdivisions and were useful in all seven diagnosis groups, thus constituting the final instrument, EOS-16. The most suitable recall period was three months. CONCLUSIONS: EOS-16 has been created according to the HRQoL survey guidelines with a versatile nationwide patient population. The survey has been validated and can be used for a wide range of chronic ear diseases as a HRQoL instrument.
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OBJECTIVES: To evaluate the suitability, benefits, and limitations of sialendoscopy for pediatric patients. METHODS: We performed a retrospective analysis of all pediatric sialendoscopy patients (aged 16 years or younger) in our tertiary care institution between September 2007 and October 2018. We characterized patient data, procedure-related factors, complications, and outcomes. RESULTS: In total, 55 sialendoscopies were performed on 42 patients. Among these, 36 were diagnostic endoscopies and 19 were interventional. Five endoscopies were performed under local anesthesia. We identified 16 sialolithiasis patients, where removal of a sialolith was possible in 11 (69%) cases; one case required a second endoscopy. We removed two sialoliths under local anesthesia. Among recurrent juvenile parotitis (RJP) patients, 18/20 (90%) were symptom-free after a single sialendoscopy, and all after a second endoscopy. The median follow-up time was 70 months. We achieved a 95% success rate in sialendoscopies, with a failure-to-treat rate of 15%. The complication rate for the study cohort was 2%, with prolonged parotid swelling the only complication encountered. CONCLUSIONS: Sialendoscopy represented a safe and effective method to treat pediatric patients. Local anesthesia was successful in selected cases, even for sialolith removal. Sialendoscopy had a soothing effect on RJP and the majority of sialoliths were suitable for endoscopic removal.
Assuntos
Anestesia Local , Edema/epidemiologia , Endoscopia , Complicações Pós-Operatórias/epidemiologia , Cálculos das Glândulas Salivares/diagnóstico , Cálculos das Glândulas Salivares/cirurgia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos , Centros de Atenção Terciária , Resultado do TratamentoRESUMO
BACKGROUND: It is known that immunologic factors are involved in the regulation of the growth of ovarian carcinoma and that granulocytes are often found on the site of ovarian cancer. Therefore, we chose to investigate the effects of cytokines on UT-OC-2 ovarian endometrioid adenocarcinoma cells in vitro. In order to investigate the molecular mechanisms involved, the activation of two key DNA-binding proteins, AP-1 and transcription factor NF-kappaB (NF-kappaB), was studied. Since DNA extracted from the UT-OC-2 cells showed fragmentation typical of apoptosis, we also studied the effects of cytokines on this event. METHODS: The effects of the studied cytokines on the proliferation of UT-OC-2 cells were investigated by (125)I-deoxyuridine incorporation. The activation of DNA-binding proteins was studied by electrophoretic mobility shift assay. Statistical analyses were performed by Student's t-test. RESULTS: Interferon alpha (IFN-alpha), transforming growth factor beta(1) (TGF-beta(1)), tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) all had a significant inhibitory effect on cell proliferation. Granulocyte colony stimulating factor (GM-CSF) did not alter cell proliferation significantly. Transcription factors AP-1 and NF-kappaB were both found to be constitutively active in UT-OC-2 ovarian carcinoma cells. We were able to show that IFN-gamma, TGF-beta(1) and TNF-alpha all increased the binding activity of transcription factor AP-1 (AP-1). The binding activity of transcription factor NF-kappaB was not altered by any of the cytokines studied, with the exception of IFN-gamma. IFN-gamma had also a clear inhibitory effect on the apparent magnitude of apoptosis, whereas TNF-alpha and TGF-beta(1) showed no effect. CONCLUSION: The results of this study show that TNF-alpha, TGF-beta(1), and IFN-gamma are able to inhibit the proliferation of UT-OC-2 ovarian carcinoma cells. Activation of AP-1 seems to be involved in the growth-regulating processes induced by IFN-gamma, TGF-beta(1) and TNF-alpha; IFN-gamma is also able to increase the binding activity of NF-kappaB and inhibited apoptosis in ovarian cancer cells.
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Apoptose/imunologia , Carcinoma Endometrioide/imunologia , Citocinas/imunologia , Neoplasias Ovarianas/imunologia , Apoptose/efeitos dos fármacos , Carcinoma Endometrioide/patologia , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Citocinas/farmacologia , Desoxiuridina/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Feminino , Humanos , NF-kappa B/imunologia , Neoplasias Ovarianas/patologia , Fator de Transcrição AP-1/imunologiaRESUMO
OBJECTIVE: To assess patient injury characteristics and contributing factors in otology. METHODS: Data on the accepted patient-injury claims involving otorhinolaryngology (ORL), closed between 2001 and 2011, from the Finnish Patient Insurance Centre registry was retrieved. We included all injuries concerning otology, with evaluation and classification of their causes and types. RESULTS: During the 10-year study period, a total of 44 claims were accepted as compensated patient injuries in otology. From a total of 233 patient injuries in all ORL, this amounted to 19%. In outpatient care, occurred 12 (27%) injuries and in surgical procedures 32 (73%). Five (11%) patients were children. Errors in surgical technique were identified as the primary cause of the injury in 22 (69%) operation-related cases. Failure to remove all auricular tampons or packing in postoperative control was a contributing factor in 4 (13%) injuries, a facial nerve was damaged in 9 (28%) operations, and in 12 (38%) patients, the injury resulted in severe hearing loss or deafness. Six patients (21%) needed one or more re-operations related to the injury, of which two were due to an incomplete primary operation. CONCLUSION: Typical compensated patient injuries in operative otology resulted from common complications of common operations in high volume centres.
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Doença Iatrogênica/epidemiologia , Complicações Intraoperatórias/epidemiologia , Otolaringologia/estatística & dados numéricos , Procedimentos Cirúrgicos Otológicos/efeitos adversos , Adulto , Criança , Traumatismos do Nervo Facial/epidemiologia , Finlândia/epidemiologia , Perda Auditiva/epidemiologia , Perda Auditiva/etiologia , Humanos , Erros Médicos/estatística & dados numéricos , Procedimentos Cirúrgicos Otológicos/estatística & dados numéricos , Estudos RetrospectivosRESUMO
Objectives To evaluate the incidence and nature of complications associated with diagnostic and interventional sialendoscopies and to report intervention failures in a prospective setup. Study Design Prospective observational study. Setting Academic tertiary care university hospital. Subjects and Methods Patients who underwent diagnostic or interventional sialendoscopy between October 2015 and December 2016 were prospectively enrolled. Patient data, operation-related factors, treatment failures, and complications were recorded into a database and analyzed. Results A total of 140 sialendoscopies were attempted or performed on 118 patients; 67 (48%) were for a parotid gland and 73 (52%) for a submandibular gland. The sialendoscopy was interventional in 81 cases (58%), diagnostic in 56 (40%), and not possible to perform in 3 (2.1%). A total of 21 complications were registered for 21 sialendoscopies (15%) and 21 patients (18%). The most common complication was infection, in 9 cases (6.4%). Other observed complications were salivary duct perforation (4 cases), prolonged glandular swelling (3 cases), transient lingual nerve analgesia (2 cases), basket entrapment (2 cases), and transient weakness in the marginal branch of the facial nerve (1 case). All complications were related to interventional procedures or papilla dilatation. Failure to treat occurred in 21 (15%) sialendoscopies: sialendoscopy itself was unsuccessful in 3 cases, and an intended intervention failed in 18 cases. Conclusion Complications in sialendoscopy are usually related to interventional procedures. The complications are mainly minor and temporary but lead to additional follow-up visits, further treatments, and sometimes hospitalization. Sialendoscopic procedures are safe but not free of complications.
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Endoscopia/efeitos adversos , Cálculos Salivares/diagnóstico por imagem , Cálculos Salivares/cirurgia , Glândulas Salivares/diagnóstico por imagem , Sialadenite/diagnóstico por imagem , Sialadenite/cirurgia , Adulto , Idoso , Endoscopia/métodos , Feminino , Seguimentos , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/fisiopatologia , Prevalência , Estudos Prospectivos , Ductos Salivares/cirurgia , Glândulas Salivares/patologia , Glândulas Salivares/cirurgia , Fatores de TempoRESUMO
BACKGROUND: A parotid abscess is a rare complication of acute suppurative parotitis which most often requires hospitalization, intravenous antibiotic therapy, and surgical drainage. OBJECTIVE: To investigate the clinical picture, treatment, and prognosis of children with a parotid abscess in a search for optional clinical guidelines for treatment. METHODS: A retrospective chart review was performed for 10 children (ageAssuntos
Abscesso/diagnóstico
, Doenças Parotídeas/microbiologia
, Abscesso/cirurgia
, Adolescente
, Antibacterianos/uso terapêutico
, Bactérias Aeróbias/classificação
, Branquioma/diagnóstico
, Criança
, Pré-Escolar
, Fístula Cutânea/microbiologia
, Drenagem
, Feminino
, Seguimentos
, Infecções por Bactérias Gram-Positivas/diagnóstico
, Neoplasias de Cabeça e Pescoço/diagnóstico
, Humanos
, Masculino
, Paracentese
, Doenças Parotídeas/cirurgia
, Glândula Parótida/cirurgia
, Parotidite/complicações
, Prognóstico
, Recidiva
, Estudos Retrospectivos
, Ruptura Espontânea
, Tuberculose Bucal/diagnóstico
, Ultrassonografia de Intervenção
RESUMO
CONCLUSIONS: In most cases, both diagnostic and interventional sialendoscopy are well tolerated under local anaesthesia (LA) or under local anaesthesia with sedation (LAS), with reasonably low patient-reported discomfort. Sialendoscopy can be considered a patient-friendly and relatively painless, gland-preserving, minimally invasive procedure suitable for day surgery. OBJECTIVE: To investigate patient experience and compliance in sialendoscopy under LA/LAS. METHODS: This prospective study was conducted at an academic tertiary-care university hospital. During a period of 22 months, 89 patients between ages 16-81 years underwent diagnostic or interventional sialendoscopy under LA (20%) or LAS (80%). After the operation the patients filled in a questionnaire formulated by the authors concerning their procedure-related experiences. Patients' demographic data, ASA status score, pre- and intra-operative blood pressure and heart rate measurements, affected gland, operation time, intervention type, as well as pre-, peri-, and postoperative medication were gathered later from the medical records. RESULTS: The level of discomfort and pain experienced during the operation was assessed as 'mild' or 'none' by 85% and 89% of the patients, respectively. The level of pain experienced after the operation was 'major' in 4% of patients and 'mild' or 'none' in the majority (87%) of patients. The patients' estimations showed no significant difference between the diagnostic and interventional procedures, although it seems that patients who underwent stone removal by transoral incision experienced the operation as a bit more uncomfortable and painful than other patients. Afterwards 97% of patients stated that they would agree to a new LA/LAS sialendoscopy in the future if needed.