RESUMO
OBJECTIVES: The aim of this study was to assess safety and efficacy of a non-invasive 2940 nm Er:YAG treatment with SMOOTH mode in reducing snoring in adult patients and to compare its efficacy and safety to sham treatment in a randomized controlled trial setting. METHODS: 40 primary snoring patients (≥ 18 year, AHI < 15e/h, BMI ≤ 30) were randomized to receive either 3 sessions NightLase or sham laser treatment. The main outcome measures were Snore Outcomes Survey (SOS), the Spouse/Bed Partner Survey (SBPS), a visual analogue snoring scale (bed partner) and a visual analogue pain scale. RESULTS: NightLase was well tolerated, no local anaesthesia was required (mean VAS pain score in NightLase group = 3.0 ± 1.7). No complications occurred. SOS, SBPS and VAS snoring scores improved in the NightLase group (33.7 ± 14.1 to 56.2 ± 16.1) (35.0 ± 17.1 to 61.5 ± 16.4) and (7.9 ± 2.0 to 4.7 ± 2.8) while no changing in the sham group (32.2 ± 14.5 vs 32.1 ± 13.0) (36.7 ± 12.1 vs 34.7 ± 12.7) (8.1 ± 1.7 vs 8.0 ± 1.6), respectively. CONCLUSIONS: NightLase is a safe, minimal invasive treatment that significantly reduced snoring compared to sham treatment.
Assuntos
Lasers de Estado Sólido , Adulto , Humanos , Lasers de Estado Sólido/uso terapêutico , Ronco/cirurgia , Inquéritos e Questionários , Resultado do TratamentoRESUMO
OBJECTIVES: Hypoglossal nerve stimulation is an effective treatment option for obstructive sleep apnea (OSA) in positive airway pressure therapy failure. Nonetheless, data regarding the functional effect of modifying stimulation parameters within each electrode configuration are limited. MATERIALS AND METHODS: In a retrospective study of 76 patients with 12 months or more follow-up, functional tongue protrusion thresholds were compared for pulse width and frequency configurations of 90 µsec 33 Hz vs 120 µsec 40 Hz. The number of tolerated voltage amplitude steps between sensation, functional, and subdiscomfort thresholds were assessed for both settings as well as impedances. RESULTS: The overall cohort showed improvement in OSA metrics: median apnea-hypopnea index from 30.0/hour to 18.6/hour and Epworth Sleepiness Scale from 13.5 to 7.6. For both bipolar and unipolar electrode configurations, the stimulation amplitude required for functional tongue protrusion was significantly reduced when the pulse width and frequency were converted from 90 µsec 33 Hz to 120 µsec 40 Hz (p < 0.001). Nevertheless, the number of voltage amplitude steps from sensation, functional, to subdiscomfort thresholds did not differ between the two settings. The ratio of automatically derived impedances between bipolar and unipolar electrode configurations was relevantly correlated with the ratio of functional thresholds at these parameters. CONCLUSION: Changing the stimulation parameters may lower the voltage requirements while maintaining the same effect on tongue protrusion. Changing these stimulation parameters does not affect the range of tolerated impulse steps between functional and subdiscomfort thresholds. Future technical appliances could help estimate functional thresholds at different electrode configurations for each patient by automatically measuring impedances.
Assuntos
Terapia por Estimulação Elétrica , Apneia Obstrutiva do Sono , Humanos , Nervo Hipoglosso/fisiologia , Estudos Retrospectivos , Língua/inervação , Terapia por Estimulação Elétrica/efeitos adversos , Apneia Obstrutiva do Sono/terapiaRESUMO
OBJECTIVES/HYPOTHESIS: Selective upper airway stimulation (sUAS) is a well-established treatment option for obstructive sleep apnea (OSA). This study aimed to determine if there are benefits in performing a home sleep test (HST) to evaluate postoperative sUAS effectiveness after patient acclimatization compared to the generally used polysomnography (PSG) titration, as measured by long-term follow-up outcomes. STUDY DESIGN: Retrospective comparative cohort analysis. METHODS: We conducted an analysis of consecutive patients at our center who had completed a 6-month follow-up (month 6 [M6]) and recorded data from M6, month 12 (M12), and month 24 (M24). After device activation, we performed an HST with the patient's stimulation settings, and measured the apnea-hypopnea index (AHI), Epworth Sleepiness Scale (ESS), and device usage. These values were compared to patients who had undergone PSG-based device titration. RESULTS: Baseline values of the initial 131 patients show high ESS and moderate OSA. At the 2-month time point of the HST, nearly half of the patients (46.2%) reached an AHI ≤15/hr, and approximately a fifth (19.2%) reached <5/hr. The PSG and HST groups differed in median ESS at M24, but no other differences were observed for ESS at M6 and M12. Both groups showed similar AHI, oxygen desaturation, and usage hours per week. CONCLUSIONS: Adjusting therapy by using the HST technique after device activation and acclimatization has clinical and economic advantages. These advantages are contingent on several conditions being met when deviating from the standard device protocol, including precise communication with the referring sleep medicine physicians, especially their role in helping with long-term follow-up. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1375-E1379, 2021.
Assuntos
Terapia por Estimulação Elétrica/instrumentação , Nervo Hipoglosso/cirurgia , Neuroestimuladores Implantáveis/estatística & dados numéricos , Apneia Obstrutiva do Sono/terapia , Feminino , Seguimentos , Humanos , Nervo Hipoglosso/fisiopatologia , Neuroestimuladores Implantáveis/efeitos adversos , Laringe/fisiopatologia , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos , Polissonografia/métodos , Polissonografia/estatística & dados numéricos , Respiração com Pressão Positiva/métodos , Respiração com Pressão Positiva/estatística & dados numéricos , Período Pós-Operatório , Estudos Retrospectivos , Sono/fisiologia , Apneia Obstrutiva do Sono/fisiopatologia , Traqueia/fisiopatologia , Resultado do TratamentoRESUMO
BACKGROUND: Upper Airway Stimulation (UAS) is a well-established therapy option for obstructive sleep apnea (OSA). AIMS: There are no data on whether respiratory sensing contributes to successful UAS therapy. MATERIALS & METHODS: After initial measurements of 3 implanted patients (M1), the sensing signal was inverted (M2) without changing other parameters. Two weeks later, the signal was converted back again, and the sensitivity of breathing cycle detection was turned to a very low state (M3). RESULTS: At M2 and M3, the apnea-hypopnea index and oxygen desaturation index increased. DISCUSSION: Correct respiratory sensing is important for controlling OSA using UAS. CONCLUSIONS: Therefore, implant centers should should optimize respiratory sensing placement and adjustment.
RESUMO
OBJECTIVE: Upper airway stimulation (UAS) is an effective second-line treatment for obstructive sleep apnea (OSA). In certain patients, there is a considerable need for advanced programming, notably with inadequate palatal response to therapy. The aim of the study was to investigate the impact of uvulopalatopharyngoplasty and tonsillectomy (UPPP-TE) on UAS therapy outcomes from a 2-year perspective after implantation. METHODS: This study included all consecutive patients implanted with UAS in which a full set of 1- and 2-year follow-up assessments (M12 and M24) were obtained. Cases were analyzed in three groups: patients with UPPP-TE after (group 1) and before (group 2) UAS, and those without UPPP-TE (group 3). RESULTS: Therapy success could be achieved in about 80% of the entire cohort. Groups 2 and 3 did not differ significantly with regard to obesity, Apnea-Hypopnea Index, or Oxygen Desaturation Index. With regard to initial sleep endoscopy, there were fewer patients without any obstruction at the palatal and oropharyngeal levels and higher prevalence of lateral obstruction patterns at oropharynx in group 1 in contrast to groups 2 and 3. Groups 2 and 3 showed similar results, although group 2 patients underwent UPPP-TE before UAS implantation. CONCLUSION: UPPP-TE should be considered in patients with persistent OSA after UAS implantation if the obstruction is identified at the level of velum and oropharynx. Although this approach has higher response rates and better outcomes can be achieved in patients with UAS, there is no indication for patients to routinely undergo UPPP-TE prior to UAS implantation. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:514-518, 2019.
Assuntos
Terapia por Estimulação Elétrica/métodos , Eletrodos Implantados , Procedimentos de Cirurgia Plástica/métodos , Apneia Obstrutiva do Sono/terapia , Tonsilectomia/estatística & dados numéricos , Estudos de Coortes , Terapia por Estimulação Elétrica/instrumentação , Endoscopia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Palato/fisiopatologia , Palato/cirurgia , Faringe/fisiopatologia , Faringe/cirurgia , Período Pós-Operatório , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/fisiopatologia , Resultado do Tratamento , Úvula/fisiopatologia , Úvula/cirurgiaRESUMO
Upper airway stimulation is a new and effective second-line treatment for obstructive sleep apnea, but possible consequences on glucose metabolism and central regulation of food intake are unclear. Twenty patients were prospectively studied before and 12â months after obstructive sleep apnea treatment by upper airway stimulation. Respiratory parameters and daytime sleepiness were assessed to document effectiveness of treatment. Glucose metabolism was assessed by the oral glucose tolerance test, and hedonic versus homeostatic drive to eat was characterized. At 12â months, upper airway stimulation significantly improved measures of obstructive sleep apnea (all pâ <â 0.01). Despite no change in body weight, fasting C-peptide insulin resistance index (pâ =â 0.01) as well as insulin and C-peptide levels at 60â min during the oral glucose tolerance test (pâ <â 0.02) were reduced. Hedonic drive to eat was strongly reduced (pâ <â 0.05), while leptin and ghrelin remained unchanged (pâ >â 0.15). Upper airway stimulation is effective in treatment of obstructive sleep apnea and improves glucose metabolism. Reduced hedonic drive to eat might contribute to these metabolic improvements. These promising findings are in need for long-term controlled evaluation of metabolic sequelae of upper airway stimulation and to mechanistically evaluate the metabolic benefits of upper airway stimulation in patients with obstructive sleep apnea.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Glucose/metabolismo , Fome/fisiologia , Qualidade de Vida/psicologia , Apneia Obstrutiva do Sono/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Apneia Obstrutiva do Sono/fisiopatologia , Resultado do TratamentoRESUMO
OBJECTIVE: Selective upper airway stimulation (sUAS) is a new treatment modality for patients with obstructive sleep apnea (OSA) and continuous positive airway pressure (CPAP) failure. The aim of this study was to analyze therapy adherence and to structure patient experience reports. METHODS: Patients from two German implantation centers were included. Besides demographic and OSA characteristics of that cohort, patients answered a questionnaire on subjective sensation of the stimulation, use of different functions, side effects, and an inventory for the description of the attitude towards sUAS. The use of the sUAS was evaluated as a read-out of the implanted system. RESULTS: The overall apnea-hypopnea-index (AHI) of that 102 assessed patients reduced from initially 32.8/h to 12.6/h at the last available assessment. The responder rate was 75%. There was an objective therapy usage of 5.7 h and subjective reports of 6.8 nights per week. The attitude resulted in strong agreement towards the statement "UAS reduces the problems caused by my sleep apnea". Information on sensing the stimulation and usage habits could be gathered such as that stimulation is only sensed by 67.9% of the patients upon waking in the morning and that 73.6% of the patients do not change the voltage in general. CONCLUSION: This investigation on the sUAS therapy revealed a high adherence to the therapy. The AHI or daytime sleepiness do not have obvious influence on adherence. Patients expressed a positive attitude towards sUAS. These patient reports upon stimulation experiences are of great help to consult candidates for sUAS in future.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Terapia por Estimulação Elétrica/métodos , Nervo Hipoglosso/fisiopatologia , Cooperação do Paciente , Satisfação do Paciente , Apneia Obstrutiva do Sono/terapia , Adulto , Idoso , Terapia Combinada , Terapia por Estimulação Elétrica/efeitos adversos , Terapia por Estimulação Elétrica/instrumentação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Próteses e Implantes , Apneia Obstrutiva do Sono/fisiopatologia , Inquéritos e Questionários , Língua/inervação , Resultado do TratamentoRESUMO
Circulating anti-neutrophilic cytoplasmic autoantibodies targeting proteinase 3 (PR3-ANCA) are a diagnostic and pathogenic hallmark of granulomatosis with polyangiitis (GPA). It is, however, incompletely understood if inflamed tissue supports presence or emergence of PR3-ANCA+ B cells. In search of such cells in inflamed tissue of GPA, immunofluorescence staining for IgG and a common PR3-ANCA idiotype (5/7 Id) was undertaken. Few 5/7 Id+/IgG+ B cells were detected in respiratory and kidney tissue of GPA. To gain more insight into surrogate markers possibly indicative of an anti-PR3-response, a meta-analysis comprising IGVH and IGVL genes derived from respiratory tract tissue of GPA (231 clones) was performed. Next generation sequencing-based IGHV genes derived from peripheral blood of healthy donors (244.353 clones) and previously published IGLV genes (148 clones) served as controls. Additionally, Ig genes of three murine and five known human monoclonal anti-PR3 antibodies were analyzed. Primary and probably secondary rearrangements led to altered VDJ usage and an extended complementarity determining region 3 (CDR3) of IGHV clones from GPA tissue. Selection against amino acid exchanges was prominent in the framework region of IGHV clones from GPA tissue. The comparison of V(D)J rearrangements and deduced amino acid sequences of the CDR3 yielded no identities and few similarities between clones derived from respiratory tissue of GPA and anti-PR3 antibodies, arguing against a presence of B cells that carry PR3-ANCA-prone Ig genes among the clones. In line with the scarcity of 5/7 Id+ B lymphocytes in GPA tissue, the results suggest that with respect to a local anti-PR3 response, methods detecting rare clones are required.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos/biossíntese , Anticorpos Monoclonais/biossíntese , Linfócitos B/imunologia , Granulomatose com Poliangiite/imunologia , Região Variável de Imunoglobulina/biossíntese , Mieloblastina/análise , Motivos de Aminoácidos , Animais , Linfócitos B/patologia , Feminino , Granulomatose com Poliangiite/genética , Granulomatose com Poliangiite/patologia , Humanos , Região Variável de Imunoglobulina/química , Rim/imunologia , Rim/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Mieloblastina/genética , Mieloblastina/imunologia , Neutrófilos/imunologia , Neutrófilos/patologia , Motivos de Nucleotídeos , Sistema Respiratório/imunologia , Sistema Respiratório/patologia , Recombinação V(D)JRESUMO
OBJECTIVE: Selective stimulation of the hypoglossal nerve has proven to be an effective therapy for patients with obstructive sleep apnea (OSA). The aim of the study is to investigate the efficacy of selective upper airway stimulation (sUAS) in older adults. METHODS: All consecutive patients older than 64 years and who received an implant for sUAS were enrolled. As a control group, an equal number of patients younger than 65 years with matched apnea hypopnea index (AHI) and body-mass-index (BMI) were selected. Treatment outcome data were collected including daytime sleepiness as well as demographics with co-morbidities, BMI, adverse events and adherence to therapy. RESULTS: 62 patients were included. Both the control and study group did not differ significantly for AHI, BMI, and Epworth Sleepiness Scale (ESS) (28.7-28.4/h; 30.1 to 28.4â¯kg/m2; 14.6 to 12.0 points); but co-morbidities were significantly higher in the study group. Our data showed no significant difference between the outcomes of study and control group for AHI, Oxygen desaturation index (ODI) and ESS (6.0-6.0/h; 7.9 to 5.5/h; 5.0 to 7.0 points). Serious adverse events did not occur in both groups and surgical implantation time did not differ. CONCLUSION: sUAS leads to significant reductions of AHI, ODI and ESS in older patients. Despite higher age and more co-morbidities, surgical implantation time was not affected. Older patients showed higher usage of sUAS. Advanced age seems not to be a limiting factor for treatment outcomes of sUAS, thus indication for this treatment can also be applied to older people.
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Terapia por Estimulação Elétrica/métodos , Apneia Obstrutiva do Sono/terapia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Terapia por Estimulação Elétrica/efeitos adversos , Feminino , Humanos , Nervo Hipoglosso/fisiopatologia , Neuroestimuladores Implantáveis , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Cooperação do Paciente , Polissonografia , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/diagnósticoRESUMO
PURPOSE: Upper airway stimulation (UAS) is an alternative second-line treatment option for patients with obstructive sleep apnea (OSA). In our substudy of a previous multicentre study of patients implanted with UAS, we focused on patient-related outcomes like Epworth Sleepiness Scale (ESS), the Functional Outcomes of Sleep Questionnaire (FOSQ), snoring and personal satisfaction 6 and 12 months after the implantation. METHODS: 60 patients, who were initially non-adherent to CPAP and implanted with UAS, were included in a prospective multicentre study. Data were collected preoperative, 6 and 12 months after implantation regarding FOSQ, ESS, snoring, and their experience with the UAS device. RESULTS: Besides relevant Apnoea-Hypopnea Index (AHI) reduction, we saw significant improvements in ESS (p < 0.001), FOSQ (p < 0.001) and snoring under UAS therapy. A strong correlation between AHI results postoperative and the personal satisfaction of the patients after implantation was found as well as between usage results and AHI compared to the preoperative results. CONCLUSION: The more the patients benefit from UAS according to their self-reported outcome, the higher is the therapy use.
Assuntos
Terapia por Estimulação Elétrica/instrumentação , Apneia Obstrutiva do Sono/terapia , Adulto , Feminino , Alemanha , Humanos , Laringe/fisiopatologia , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Vigilância de Produtos Comercializados , Estudos Prospectivos , Autorrelato , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/fisiopatologia , Ronco/etiologia , Ronco/prevenção & controle , Inquéritos e Questionários , Resultado do TratamentoRESUMO
PURPOSE: The aim of this work was to assess whether uvulopalatopharyngoplasty in patients with failure for positive airway pressure not only reduces the degree of obstructive sleep apnea but also to determine as well if it changes the collapse pattern of the soft palate and thereby fulfills the qualifications for implementing upper airway stimulation (UAS) as an adjunctive solution. METHOD: Fifteen patients with intolerance for positive airway pressure were included in this retrospective cohort study. Polygraphy and drug-induced sleep endoscopy were used in order to evaluate the reduction of the apnea-hypopnea index (AHI), as well as the change of collapse pattern at the soft palate level before and about 3 months after uvulopalatopharyngoplasty and tonsillectomy (TE-UPPP). RESULTS: In 93% of the patients, a postoperative change of the initially complete concentric palatal collapse pattern could be found during drug-induced sleep endoscopy. In one patient, no obstruction at all was seen at the soft palatal level. Only one patient still presented with a complete concentric collapse at velum level. AHI decreased from mean 34.7 events per hour to 20.2/h and oxygen desaturation index from 25.3 events per hour to 16.1/h. CONCLUSION: Patients seeking for positive airway pressure alternatives could not only benefit from reduction of AHI by TE-UPPP postoperatively; additionally, by changing the collapse pattern at the soft palate, they might also fulfill criteria for upper airway stimulation (UAS) in case of persistent OSA of at least moderate degree.
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Palato Mole/cirurgia , Faringe/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Apneia Obstrutiva do Sono/cirurgia , Úvula/cirurgia , Adulto , Endoscopia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Palato Mole/fisiopatologia , Faringe/fisiopatologia , Polissonografia , Estudos Retrospectivos , Apneia Obstrutiva do Sono/fisiopatologia , Resultado do Tratamento , Úvula/fisiopatologiaRESUMO
Anti-neutrophil cytoplasmic autoantibodies (ANCA) targeting proteinase 3 (PR3) and myeloperoxidase expressed by innate immune cells (neutrophils and monocytes) are salient diagnostic and pathogenic features of small vessel vasculitis, comprising granulomatosis with polyangiitis (GPA), microscopic polyangiitis, and eosinophilic GPA. Genetic studies suggest that ANCA-associated vasculitides (AAV) constitute separate diseases, which share common immunological and pathological features, but are otherwise heterogeneous. The successful therapeutic use of anti-CD20 antibodies emphasizes the prominent role of ANCA and possibly other autoantibodies in the pathogenesis of AAV. However, to elucidate causal effects in AAV, a better understanding of the complex interplay leading to the emergence of B lymphocytes that produce pathogenic ANCA remains a challenge. Different scenarios seem possible; e.g., the break of tolerance induced by a shift from non-pathogenic toward pathogenic autoantigen epitopes in inflamed tissue. This review gives a brief overview on current knowledge about genetic and epigenetic factors, barrier dysfunction and chronic non-resolving inflammation, necro-inflammatory auto-amplification of cellular death and inflammation, altered autoantigen presentation, alternative complement pathway activation, alterations within peripheral and inflamed tissue-residing T- and B-cell populations, ectopic lymphoid tissue neoformation, the characterization of PR3-specific T-cells, properties of ANCA, links between autoimmune disease and infection-triggered pathology, and animal models in AAV.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Animais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/epidemiologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Linfócitos B/imunologia , Morte Celular , Via Alternativa do Complemento , Humanos , Imunoglobulina G/imunologiaRESUMO
OBJECTIVE/HYPOTHESIS: Upper airway stimulation (UAS) of the hypoglossal nerve has been implemented in the routine clinical practice for patients with moderate-to-severe obstructive sleep apnea (OSA) who could not adhere to continuous positive airway pressure. This study reports objective and patient-reported outcome after 12 months of implantation. STUDY DESIGN: Multicenter prospective single-arm study. METHODS: Consecutive patients who received the UAS system (Inspire Medical Systems, Inc., Minneapolis, Minnesota, Maple Grove, MN, U.S.A.) were enrolled in three German centers. Key study exclusion criteria included body mass index > 35 kg/m2 , apnea-hypopnea index (AHI) < 15 or > 65, or complete concentric collapse at the soft palate during sedated endoscopy. Data collection at 6- and 12-month visit include home sleep test and patient-reported outcome measures. RESULTS: Among the total of 60 participants, the median AHI reduced from 28.6 to 9.5 from baseline to 12 months. Patient-reported outcome measured in Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire both improved significantly from baseline to 12 months. The average usage time was 39.1 ± 14.9 hours per week among all participants based on recordings by the implanted device. One patient requested a removal of the device for cosmetic and other personal reasons and was completed without sequelae. CONCLUSION: This study supported that UAS is a safe and effective treatment option for patients with OSA in routine clinical practice. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:509-515, 2018.
Assuntos
Terapia por Estimulação Elétrica/métodos , Endoscopia/métodos , Implantação de Prótese/métodos , Apneia Obstrutiva do Sono/terapia , Idoso , Feminino , Humanos , Nervo Hipoglosso/fisiopatologia , Nervo Hipoglosso/cirurgia , Neuroestimuladores Implantáveis , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Polissonografia , Estudos Prospectivos , Apneia Obstrutiva do Sono/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: This study investigated the prognostic role of nuclear expression of p65 in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) receiving post-operative radio(chemo)therapy. METHODS: Nuclear p65-expression (H-score ≤50 versus >50) plus twelve characteristics were analyzed in 151 patients for overall survival (OS), metastases-free survival (MFS) and loco-regional control (LRC). Additional characteristics included age, gender, Karnofsky performance score (KPS), pre-radiotherapy hemoglobin levels, tumor site, histological grading, human papilloma virus (HPV)-status, T-classification, N-classification, American Joint Committee on Cancer (AJCC)-stage, extent of resection and concurrent chemotherapy. Univariate analyses were performed with Kaplan-Meier method and log-rank test, multivariate analyses with Cox proportional hazards model. RESULTS: On univariate analyses, p65-expression had a significant impact on OS (p < 0.001) and LRC (p < 0.001) but not on MFS (p = 0.29). On multivariate analysis, KPS ≥80 (risk ratio [RR] 2.23; p = 0.012), HPV-positivity (RR 5.83; p = 0.020), T1-T2 (RR 1.38; p = 0.048), N0-N2a (RR 2.72; p = 0.005) and complete resection (RR 2.02; p = 0.049) were positively associated with OS; p65-negativity achieved borderline significance (RR 3.02; p = 0.052). Better MFS was associated with KPS ≥80 (RR 2.49; p = 0.015), T1-T2 (RR: 1.74; p = 0.005), N0-N2a (RR: 6.22; p < 0.001) and complete resection (RR 3.43; p = 0.003). Positive associations with LRC were found for p65-negativity (RR 5.06; p = 0.008), T1-T2 (RR: 1.49; p = 0.022), N0-N2a (RR: 2.97; p = 0.004) and favorable tumor site (RR 1.28; p = 0.025). CONCLUSIONS: P65-negativity was significantly associated with improved LRC and achieved borderline significance with respect to improved OS. Thus, p65-expression may be an additional target for novel agents in the treatment of locally advanced SCCHN.
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Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Núcleo Celular/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Fator de Transcrição RelA/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Estudos de Coortes , Terapia Combinada , Seguimentos , Expressão Gênica , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Imuno-Histoquímica , Avaliação de Estado de Karnofsky , Estadiamento de Neoplasias , Carcinoma de Células Escamosas de Cabeça e Pescoço , Análise de Sobrevida , Fator de Transcrição RelA/genética , Resultado do TratamentoRESUMO
BACKGROUND/AIM: During the treatment of head and neck cancer (HNC), salivary problems may impair a patient's healing process. Botulinum toxin (BoNT) is accepted as an effective treatment option for reducing salivary flow. We aimed to describe the features of patients treated with BoNT to determine the effects of BoNT. PATIENTS AND METHODS: Twenty-five patients over a five-year period were retrospectively included. The patients suffered at different stages of oncologic treatment. The cohort primarily had larger primary tumors that required complex oncological treatment. RESULTS: The condition improved in more than three quarters of the 19 patients with functional hypersalivation. Four of six cases suffering from a salivary fistula demonstrated an obvious reduction in symptoms. CONCLUSIONS: Injection of BoNT, to temporarily reduce saliva flow, is a safe tool in the treatment of HNC even in situations involving repeated therapy or high dosage. The main clinical side-effect of BoNT is insufficient reduction of the salivary problem.
Assuntos
Toxinas Botulínicas/uso terapêutico , Neoplasias de Cabeça e Pescoço/complicações , Recidiva Local de Neoplasia/tratamento farmacológico , Neurotoxinas/uso terapêutico , Sialorreia/tratamento farmacológico , Idoso , Seguimentos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Sialorreia/etiologia , Sialorreia/patologiaRESUMO
BACKGROUND AND PURPOSE: To investigate the potential prognostic role of tumor cell podoplanin expression in patients treated with resection followed by irradiation or chemoradiotherapy for locally advanced squamous cell carcinoma of the head and neck (SCCHN). MATERIALS AND METHODS: Podoplanin expression (≤10 % versus > 10 %) and 12 other factors were evaluated in 160 patients for their association with locoregional control (LRC), metastases-free (MFS) and overall survival (OS). Other factors were age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, preradiotherapy (pre-RT) hemoglobin level, tumor site, histological grading, T category, N category, American Joint Committee on Cancer (AJCC) stage, human papillomavirus (HPV) status, extent of resection and concurrent chemotherapy. RESULTS: In multivariate analysis, ECOG performance status 0-1 (risk ratio, RR: 3.01; 95 % confidence interval, CI: 1.42-7.14; p = 0.003), pre-RT hemoglobin levels ≥ 7.45 mmol/l (12 g/dl; RR: 2.03; 95 % CI: 1.04-3.94; p = 0.038), oropharyngeal cancer (RR: 1.25; 95 % CI: 1.01-1.55; p = 0.038) and T category T1-2 (RR: 1.81; 95 % CI: 1.24-2.79; p = 0.002) were significantly associated with improved LRC. T category T1-2 (RR: 1.90; 95 % CI: 1.25-3.06; p = 0.002) and N category N0-2a (RR: 5.22; 95 % CI: 1.96-18.09; p < 0.001) were significantly associated with better MFS. Pre-RT hemoglobin levels ≥ 7.45 mmol/l (RR: 2.44; 95 % CI: 1.27-4.74; p = 0.007), T category T1-2 (RR: 1.97; 95 % CI: 1.36-3.04; p < 0.001) and N category N0-2a (RR: 2.87; 95 % CI: 1.37-6.61; p = 0.005) were significantly associated with improved OS. Podoplanin expression ≤ 10 % showed a trend towards improved OS on both univariate (p = 0.050) and multivariate analysis (RR: 1.86; 95 % CI: 0.96-3.59; p = 0.07). CONCLUSION: Treatment outcomes were significantly associated with performance status, pre-RT hemoglobin level, tumor site and tumor stage. Tumor cell expression of podoplanin ≤ 10 % showed a trend towards improved OS when compared to podoplanin expression of > 10 %.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/radioterapia , Glicoproteínas de Membrana/metabolismo , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico , Feminino , Alemanha/epidemiologia , Neoplasias de Cabeça e Pescoço/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Prevalência , Prognóstico , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Carcinoma de Células Escamosas de Cabeça e Pescoço , Taxa de Sobrevida , Resultado do TratamentoRESUMO
INTRODUCTION: Plasma cells residing in inflamed tissues produce antibodies in chronic inflammatory and systemic autoimmune diseases. This study examined if plasma cells, located within inflamed nasal tissue in granulomatosis with polyangiitis (GPA), express features potentially associated with the autoimmune and destructive character of this disease. METHODS: Ig gene mutation patterns of individual tissue-derived plasma cells from GPA (n = 5) were analyzed, by using laser-assisted microdissection followed by semi-nested polymerase chain reaction (PCR). Signs of B-lymphocyte maturation (ectopic lymphoid structures, ELS) and survival (a proliferation-inducing ligand, APRIL; B-cell maturation antigen, BCMA; transmembrane-activator and calcium modulator and cyclophilin interactor, TACI; receptor activator of nuclear factor κB ligand, RANKL) were examined in nasal tissues or serum, respectively, by using immunohistochemistry/fluorescence and enzyme-linked immunosorbent assay, ELISA. RESULTS: Plasma-cell derived Ig genes (light- and heavy-chain pairs, n = 4; heavy chains, n = 33) resembled mutation patterns seen in other autoimmune diseases, predominantly displaying selection against replacement mutations within the framework region of Ig genes (10 of 15), which is responsible for structural integrity. Ectopic lymphoid structures were similar between GPA and a disease control (that is, unspecific chronic rhinosinusitis. However, histomorphologic features distinguishing GPA from rhinosinusitis (that is, neutrophilic microabscess and granuloma) expressed considerable amounts of membrane-associated and secreted APRIL, respectively. The latter was co-localized with CD138 and found in close proximity to cells expressing IgG, TACI, and BCMA. Interestingly, plasma cells strongly expressed receptor activator of nuclear factor κB ligand (RANKL), apart from fibroblast-like cells. CONCLUSIONS: Plasma cells within granulomatous inflammation appear to display features that might be required for autoreactivity and, possibly, RANKL-mediated destruction in GPA.
Assuntos
Autoimunidade/imunologia , Granulomatose com Poliangiite/imunologia , Granulomatose com Poliangiite/patologia , Inflamação/imunologia , Plasmócitos/imunologia , Ensaio de Imunoadsorção Enzimática , Genes de Imunoglobulinas/genética , Granulomatose com Poliangiite/genética , Humanos , Imuno-Histoquímica , Inflamação/patologia , Microdissecção e Captura a Laser , Plasmócitos/patologia , Reação em Cadeia da PolimeraseRESUMO
Mutations in the gene encoding podocin (NPHS2) cause autosomal recessive steroid-resistant nephrotic syndrome (SRNS). For addressing the possibility of a genotype-phenotype correlation between podocin mutations and age of onset, a worldwide cohort of 430 patients from 404 different families with SRNS were screened by direct sequencing. Recessive podocin mutations were present in 18.1% (73 of 404) of families with SRNS, and 69.9% of these mutations were nonsense, frameshift, or homozygous R138Q. Patients with these mutations manifested symptoms at a significantly earlier age (mean onset <1.75 years) than any other patient group, with or without podocin mutations, in this study (mean onset >4.17 yr). All but one patient affected by truncating or homozygous R138Q mutations developed SRNS before 6 yr of age. Patient groups with other recessive podocin mutations, with single heterozygous podocin mutations, with sequence variants, and with no podocin changes could not be distinguished from each other on the basis of age of onset. In conclusion, nephrotic syndrome in children with truncating or homozygous R138Q mutations manifests predominantly before 6 yr of life, and the onset of disease is significantly earlier than for any other podocin mutations. Because the age of onset can vary by several years among those with identical mutations, additional factors may modify the phenotype.