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PURPOSE: Asthma is a clinical syndrome with various underlying pathomechanisms and clinical phenotypes. Genetic, ethnic, and geographic factors may influence the differences in clinical presentation, severity, and prognosis. We compared the characteristics of asthma based on the geographical background by analyzing representative cohorts from the United States, Europe, South America, and Asia using the Severe Asthma Research Program (SARP), Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED), Program for Control of Asthma in Bahia (ProAR), and Cohort for Reality and Evolution of Adult Asthma in Korea (COREA), respectively. METHODS: The clinical characteristics and medications for the SARP (n = 669), U-BIOPRED (n = 509), ProAR (n = 996), and COREA (n = 3,748) were analyzed. Subgroup analysis was performed for severe asthma. RESULTS: The mean age was highest and lowest in the COREA and SARP, respectively. The asthma onset age was lowest in the ProAR. The mean body mass index was highest and lowest in the SARP and COREA, respectively. Baseline pulmonary function was lowest and highest in the U-BIOPRED and COREA, respectively. The number of patients with acute exacerbation in the previous year was highest in U-BIOPRED. The mean blood eosinophil count was highest in COREA. The total immunoglobulin E was highest in the ProAR. The frequency of atopy was highest in the SARP. The principal component analysis plot revealed differences among all cohorts. CONCLUSIONS: The cohorts from 4 different continents exhibited different clinical and physiological characteristics, probably resulting from the interplay between genetic susceptibility and geographical factors.
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Clostridioides difficile infection (CDI) is a major cause of antibiotic-associated diarrhea and colitis. It is recognized as one of the most significant hospital-acquired infections. Although CDI can develop severe complications and spores of Clostridioides difficile can be transmitted by the fecal-oral route, CDI is occasionally overlooked in clinical settings. Thus, it is necessary to monitor high CDI risk groups, particularly those undergoing antibiotic treatment, to prevent complications and spread. We developed and validated a deep learning-based model to predict the occurrence of CDI within 28 days after starting antibiotic treatment using longitudinal electronic health records. For each patient, timelines of vital signs and laboratory tests with a 35-day monitoring period and a patient information vector consisting of age, sex, comorbidities, and medications were constructed. Our model achieved the prediction performance with an area under the receiver operating characteristic curve of 0.952 (95% CI: 0.932-0.973) in internal validation and 0.972 (95% CI: 0.968-0.975) in external validation. Platelet count and body temperature emerged as the most important features. The risk score, the output value of the model, exhibited a consistent increase in the CDI group, while the risk score in the non-CDI group either maintained its initial value or decreased. Using our CDI prediction model, high-risk patients requiring symptom monitoring can be identified. This could help reduce the underdiagnosis of CDI, thereby decreasing transmission and preventing complications.
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BACKGROUND: The fatty infiltration and atrophy in the muscle after a rotator cuff (RC) tear are important in surgical decision-making and are linked to poor clinical outcomes after rotator cuff repair. An accurate and reliable quantitative method should be developed to assess the entire RC muscles. PURPOSE: To develop a fully automated approach based on a deep neural network to segment RC muscles from clinical magnetic resonance imaging (MRI) scans. MATERIAL AND METHODS: In total, 94 shoulder MRI scans (mean age = 62.3 years) were utilized for the training and internal validation datasets, while an additional 20 MRI scans (mean age = 62.6 years) were collected from another institution for external validation. An orthopedic surgeon and a radiologist manually segmented muscles and bones as reference masks. Segmentation performance was evaluated using the Dice score, sensitivities, precision, and percent difference in muscle volume (%). In addition, the segmentation performance was assessed based on sex, age, and the presence of a RC tendon tear. RESULTS: The average Dice score, sensitivities, precision, and percentage difference in muscle volume of the developed algorithm were 0.920, 0.933, 0.912, and 4.58%, respectively, in external validation. There was no difference in the prediction of shoulder muscles, with the exception of teres minor, where significant prediction errors were observed (0.831, 0.854, 0.835, and 10.88%, respectively). The segmentation performance of the algorithm was generally unaffected by age, sex, and the presence of RC tears. CONCLUSION: We developed a fully automated deep neural network for RC muscle and bone segmentation with excellent performance from clinical MRI scans.
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The diagnosis of anaphylaxis is based on the clinical history. The utility of tryptase measurements in clinical setting is limited. Mas-related G protein-coupled receptor-X2 (MRGPRX2) is expressed in mast cells and is involved in the degranulation of these cells. We evaluated the potential of MRGPRX2 as a diagnostic biomarker in patients with iodinated contrast media (ICM)-induced immediate hypersensitivity reactions (IHRs). A total of 173 patients with documented ICM-induced IHR within 4 months from registration were enrolled and skin tests for the culprit ICM were performed. The time interval was evaluated as the duration between the onset of ICM-induced IHR and the measurement of serum MRGPRX2 levels. Serum MRGPRX2 concentration was determined using an enzyme-linked immunosorbent assay kit. Of the 173 patients, 33 and 140 were included in the anaphylaxis and non-anaphylaxis groups, respectively. Serum MRGPRX2 levels were significantly higher in the anaphylaxis than in the non-anaphylaxis group (29.9 ± 24.1 vs. 20.7±17.5, P = 0.044). Serum MRGPRX2 showed a moderate predictive ability for anaphylaxis, with an area under the curve of 0.61 (P = 0.058). When groups were classified based on the time interval, T1(0-2months) and T2 (2-4months), patients with anaphylaxis had higher MRGPRX2 levels compared to the non-anaphylaxis group in the T2 group (36.5±19.2 vs. 20.5±19.0, P = 0.035). This pilot study shows that serum MRGPRX2 is a potential long-term biomarker for predicting anaphylaxis, particularly ICM-induced anaphylaxis. Further studies are needed to determine the role of MRGPRX2 in anaphylaxis in a larger population of patients with various drug-induced IHRs.
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This study aimed to investigate the effects of high-dose inhaled corticosteroids (ICS) on chronic cough patients with elevated fractional exhaled nitric oxide (FeNO) levels. In a prospective study, adults with chronic cough and FeNO ≥ 25 ppb, without any other apparent etiology, received fluticasone furoate (200 mcg) for three weeks. Outcomes were evaluated using FeNO levels, cough severity, and Leicester Cough Questionnaire (LCQ) before and after treatment. Of the fifty participants (average age: 58.4 years; 58% female), the treatment responder rate (≥ 1.3-point increase in LCQ) was 68%, with a significant improvement in cough and LCQ scores and FeNO levels post-treatment. However, improvements in cough did not significantly correlate with changes in FeNO levels. These findings support the guideline recommendations for a short-term ICS trial in adults with chronic cough and elevated FeNO levels, but the lack of correlations between FeNO levels and cough raises questions about their direct mechanistic link.
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Tosse , Óxido Nítrico , Humanos , Tosse/tratamento farmacológico , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Prospectivos , Administração por Inalação , Doença Crônica , Óxido Nítrico/metabolismo , Óxido Nítrico/análise , Idoso , Resultado do Tratamento , Teste da Fração de Óxido Nítrico Exalado , Androstadienos/administração & dosagem , Adulto , Índice de Gravidade de Doença , Inquéritos e Questionários , Expiração , Corticosteroides/administração & dosagem , Tosse CrônicaRESUMO
Background: Drug-induced hypersensitivity such as anaphylaxis is an important cause of drug-related morbidity and mortality. Cefaclor is a leading cause of drug induced type I hypersensitivity in Korea, but little is yet known about genetic biomarkers to predict this hypersensitivity reaction. We aimed to evaluate the possible involvement of genes in cefaclor induced type I hypersensitivity. Methods: Whole exome sequencing (WES) and HLA genotyping were performed in 43 patients with cefaclor induced type I hypersensitivity. In addition, homology modeling was performed to identify the binding forms of cefaclor to HLA site. Results: Anaphylaxis was the most common phenotype of cefaclor hypersensitivity (90.69%). WES results show that rs62242177 and rs62242178 located in LIMD1 region were genome-wide significant at the 5 × 10-8 significance level. Cefaclor induced type I hypersensitivity was significantly associated with HLA-DRB1∗04:03 (OR 4.61 [95% CI 1.51-14.09], P < 0.002) and HLA-DRB1∗14:54 (OR 3.86 [95% CI 1.09-13.67], P < 0.002). Conclusion: LIMD1, HLA-DRB1∗04:03 and HLA-DRB1∗14:54 may affect susceptibility to cefaclor induced type I hypersensitivity. Further confirmative studies with a larger patient population should be performed to ascertain the role of HLA-DRB1 and LIMD1 in the development of cefaclor induced hypersensitivity.
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BACKGROUND: YH35324, a long-acting IgETrap-Fc fusion protein, is a novel therapeutic agent for immunoglobulin E (IgE)-mediated allergic diseases. This randomized, double-blind, placebo/active-controlled, single ascending dose Phase 1 study assessed the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of YH35324 in subjects with atopy. METHODS: Eligible subjects were healthy subjects or atopic adults with mild allergic rhinitis, atopic dermatitis, food allergy, or urticaria, and a serum total IgE level of 30-700 IU/mL (Part A) or > 700 IU/mL (Part B). In Part A, 35 subjects in 5 cohorts received YH35324 (0.3, 1, 3, 6, and 9 mg/kg), 8 received omalizumab (300 mg), and 9 received placebo. In Part B, 8 subjects received YH35324 and 8 received omalizumab. RESULTS: Twenty subjects (38.5 %) in Part A (YH35324: 37.1 %, omalizumab: 50.0 %, placebo: 33.3 %) and 10 subjects (62.5 %) in Part B (YH35324: 100 %; omalizumab: 25.0 %) experienced treatment-emergent adverse events (TEAEs). TEAEs were mostly grade 1/2; no serious AEs, AE-related treatment discontinuation, or anaphylaxis were reported. YH35324 exhibited dose-proportional increase in Cmax and AUClast over the dose range of 0.3-9 mg/kg. YH35324 rapidly suppressed serum-free IgE levels to a significant extent (< 25 and < 82.8 ng/mL, both P < 0.05) and with longer duration than omalizumab. CONCLUSION: This study showed that YH35324 has a favorable safety profile and is effective in reducing serum-free IgE levels in subjects with atopic conditions.
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Anafilaxia , Dermatite Atópica , Adulto , Humanos , Omalizumab/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Anafilaxia/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/induzido quimicamente , Imunoglobulina E , Método Duplo-Cego , Ligante de CD40RESUMO
PURPOSE: Codeine is a narcotic antitussive often considered for managing patients with refractory or unexplained chronic cough. This study aimed to evaluate the proportion and characteristics of patients who responded to codeine treatment in real-world practice. METHODS: Data from the Korean Chronic Cough Registry, a multicenter prospective cohort study, were analyzed. Physicians assessed the response to codeine based on the timing and degree of improvement after treatment initiation. Follow-up assessments included the Leicester Cough Questionnaire and cough severity visual analog scale at six months. In a subset of subjects, objective cough frequency was evaluated following the initiation of codeine treatment. RESULTS: Of 305 patients, 124 (40.7%) responded to treatments based on anatomic diagnostic protocols, while 181 (59.3%) remained unexplained or refractory to etiological treatments. Fifty-one subjects (16.7%) were classified as codeine treatment responders (those showing a rapid and clear response), 57 (18.7%) as partial responders, and 62 (20.3%) as non-responders. Codeine responders showed rapid improvement in objective cough frequency and severity scores within a week of the treatment. At 6 months, responders showed significantly improved scores in cough scores, compared to non-responders. Several baseline parameters were associated with a more favorable treatment response, including older age, non-productive cough, and the absence of heartburn. CONCLUSIONS: Approximately 60% of chronic cough patients in specialist clinics may require antitussive drugs. While codeine benefits some, only a limited proportion (about 20%) of patients may experience rapid and significant improvement. This underscores the urgent need for new antitussive drugs to address these unmet clinical needs.
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Antitussígenos , Codeína , Humanos , Codeína/uso terapêutico , Antitussígenos/uso terapêutico , Estudos Prospectivos , Tosse Crônica , Estudos de Coortes , Tosse/tratamento farmacológico , Tosse/etiologiaRESUMO
PURPOSE: To evaluate the radiographic and clinical outcomes when rerouting a pathologic biceps during arthroscopic rotator cuff repair by comparing it with concomitant subpectoral biceps tenodesis (SPBT). METHODS: This retrospective, historical cohort study was conducted with patients who underwent an arthroscopic repair of a full-thickness rotator cuff tear, with intraoperative confirmation of biceps pathology including partial tears, subluxation, pulley lesions, or type II SLAP lesions. Until May 2018, such patients were treated with concomitant subpectoral tenodesis (group SPBT). Afterward, biceps rerouting (BR) was done regardless of biceps pathology (group BR) without biceps or SLAP repair. Radiographic parameters, including fatty degeneration, acromiohumeral distance, Sugaya classification, and retears, were evaluated using preoperative and 1-year postoperative magnetic resonance imaging results. Clinical evaluation with a minimum 2-year follow-up included pain visual analog scale, American Shoulder and Elbow Surgeons, Simple Shoulder Test, and Constant-Murley scores. Whether individual patients exceeded these scores' minimal clinically important difference also was determined. RESULTS: A total of 64 patients (group SPBT = 32; group BR = 32) were included in the final analysis. The duration of clinical follow-up was 36.2 ± 9.3 months in group SPBT and 29.4 ± 6.9 months in the BR group (P = .002). Compared with group SPBT, group BR demonstrated a significantly lower retear rate (SPBT vs BR: 34.4% vs 12.5%, P = .039). In the BR group, 8 of 32 (25%) patients demonstrated a postoperative LHBT tear. The 4 cuff retears in group BR only took place within these patients. Other postoperative radiographic and clinical outcomes were comparable between the groups. Within each group, significant postoperative improvements were demonstrated (P < .05 for all clinical scores). CONCLUSIONS: Even in the presence of a pathologic LHBT and/or a type II SLAP lesion, augmenting the rotator cuff repair with BR significantly reduced retear rates while achieving clinical scores comparable with SPBT in a minimum 2-year follow-up. LEVEL OF EVIDENCE: Level III, retrospective comparative study.
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Artroscopia , Lesões do Manguito Rotador , Tenodese , Humanos , Tenodese/métodos , Estudos Retrospectivos , Lesões do Manguito Rotador/cirurgia , Lesões do Manguito Rotador/diagnóstico por imagem , Feminino , Pessoa de Meia-Idade , Masculino , Artroscopia/métodos , Resultado do Tratamento , Idoso , Músculo Esquelético/cirurgia , Músculo Esquelético/diagnóstico por imagem , Recidiva , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: The determinants linked to the short- and long-term improvement in lung function in patients with severe eosinophilic asthma (SEA) on biological treatment (BioT) remain elusive. OBJECTIVE: We sought to identify the predictors of early and late lung function improvement in patients with SEA after BioT. METHODS: 140 adult patients with SEA who received mepolizumab, dupilumab, or reslizumab were followed up for 6 months to evaluate improvement in forced expiratory volume in one second (FEV1). Logistic regression was used to determine the association between potential prognostic factors and improved lung function at 1 and 6 months of treatment. RESULTS: More than a third of patients with SEA using BioT showed early and sustained improvements in FEV1 after 1 month. A significant association was found between low baseline FEV1 and high blood eosinophil count and sustained FEV1 improvement after 1 month (0.54 [0.37-0.79] and 1.88 [1.28-2.97] odds ratios and 95% confidence interval, respectively). Meanwhile, among patients who did not experience FEV1 improvement after 1 month, 39% exhibited improvement at 6 months follow-up. A high ACT score measured at this visit was the most reliable predictor of late response after 6 months of treatment (OR and 95% CI 1.75 [1.09-2.98]). CONCLUSION: Factors predicting the efficacy of biological agents that improve lung function in SEA vary according to the stage of response.
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Antiasmáticos , Asma , Produtos Biológicos , Eosinofilia Pulmonar , Adulto , Humanos , Antiasmáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Eosinófilos , Eosinofilia Pulmonar/tratamento farmacológico , PulmãoRESUMO
PURPOSE: This study aimed to advance the MetaLAB algorithm and verify its performance with multicenter data to effectively detect major adverse drug reactions (ADRs), including drug-induced liver injury. METHODS: Based on MetaLAB, we created an optimal scenario for detecting ADRs by considering demographic and clinical records. MetaLAB-HOI was developed to identify ADR signals using common model-based multicenter electronic health record (EHR) data from the clinical health outcomes of interest (HOI) template and design for drug-exposed and nonexposed groups. In this study, we calculated the odds ratio of 101 drugs for HOI in Konyang University Hospital, Seoul National University Hospital, Chungbuk National University Hospital, and Seoul National University Bundang Hospital. RESULTS: The overlapping drugs in four medical centers are amlodipine, aspirin, bisoprolol, carvedilol, clopidogrel, clozapine, digoxin, diltiazem, methotrexate, and rosuvastatin. We developed MetaLAB-HOI, an algorithm that can detect ADRs more efficiently using EHR. We compared the detection results of four medical centers, with drug-induced liver injuries as representative ADRs. CONCLUSIONS: MetaLAB-HOI's strength lies in fully utilizing the patient's clinical information, such as prescription, procedure, and laboratory results, to detect ADR signals. Considering changes in the patient's condition over time, we created an algorithm based on a scenario that accounted for each drug exposure and onset period supervised by specialists for HOI. We determined that when a template capable of detecting ADR based on clinical evidence is developed and manualized, it can be applied in medical centers for new drugs with insufficient data.
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Doença Hepática Induzida por Substâncias e Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Sistemas de Notificação de Reações Adversas a Medicamentos , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Registros Eletrônicos de Saúde , Hospitais Universitários , Avaliação de Resultados em Cuidados de Saúde , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: Although various monoclonal antibodies have been used as add-on therapy for severe eosinophilic asthma (SEA), to the best of our knowledge, no direct head-to-head comparative study has evaluated their efficacy. OBJECTIVE: To compare the efficacy of reslizumab, mepolizumab, and dupilumab in patients with SEA. METHODS: This was a multicenter, prospective observational study in patients with SEA who had received 1 of these biologic agents for at least 6 months. Cox proportional hazard models were used to compare the risk of the first exacerbation event, adjusting for sputum or blood eosinophils and common asthma-related covariates. The annual exacerbation rate was analyzed using a negative binomial model, and a mixed-effect model was used to analyze changes in forced expiratory volume in 1 second and asthma control test score over time. RESULTS: A total of 141 patients with SEA were included in the analysis; 71 (50%) received dupilumab; 40 (28%) received reslizumab, and 30 (21%) received mepolizumab. During the 12-month follow-up, 27.5%, 43.3%, and 38.0% of patients in the reslizumab, mepolizumab, and dupilumab groups, respectively, experienced at least 1 exacerbation. However, after adjusting for confounding factors, the dupilumab and mepolizumab groups showed similar outcomes in time-to-first exacerbation, exacerbation rate, forced expiratory volume in 1 second, and asthma control test score to those of the reslizumab group. CONCLUSION: In patients with SEA, treatment with reslizumab, mepolizumab, and dupilumab resulted in comparable clinical outcomes within a 12-month period. TRIAL REGISTRATION: The cohort protocol was sanctioned by the Institutional Review Board of each study center (clinicaltrial.gov identifier NCT05164939).
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Antiasmáticos , Asma , Produtos Biológicos , Eosinofilia Pulmonar , Humanos , Estudos Prospectivos , Eosinófilos , Anticorpos Monoclonais/uso terapêutico , Eosinofilia Pulmonar/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Antiasmáticos/uso terapêuticoRESUMO
The current emergence of the coronavirus disease 2019 (COVID-19) pandemic and the possible side effects of COVID-19 mRNA vaccination remain worrisome. Few cases of vaccination-related side effects, such as vasculitis, have been reported. Eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg-Strauss syndrome, is a type of vasculitis characterized by the histological richness of eosinophils, asthma, polyneuropathy, sinusitis, and skin or lung involvement. Here, we report the first case of new onset EGPA following COVID-19 vaccination in Korea. A 71-year old woman developed a skin rash and presented with progressive weakness of the upper and lower extremities after the BNT162b2 vaccination (Pfizer-BioNTech). She was diagnosed with EGPA and her symptoms improved after systemic steroid and immunosuppressant therapy. Although it is very rare, clinicians should be aware that EGPA may occur after COVID-19 vaccination.
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Vacinas contra COVID-19 , COVID-19 , Síndrome de Churg-Strauss , Granulomatose com Poliangiite , Idoso , Feminino , Humanos , Vacina BNT162 , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/etiologia , Síndrome de Churg-Strauss/tratamento farmacológico , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/terapiaRESUMO
Background: Despite the increasing use of biologics in severe asthma, there is limited research on their use in asthma-chronic obstructive pulmonary disease overlap (ACO). We compared real-world treatment responses to biologics in ACO and asthma. Methods: We conducted a multicenter, retrospective, cohort study using data from the Precision Medicine Intervention in Severe Asthma (PRISM). ACO was defined as post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7 and a smoking history of >10 pack-years. Physicians selected biologics (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) based on each United States Food & Drug Administration (FDA) approval criteria. Results: After six-month treatment with biologics, both patients with ACO (N = 13) and asthma (N = 81) showed positive responses in FEV1 (10.69 ± 17.17 vs. 11.25 ± 12.87 %, P = 0.652), Asthma Control Test score (3.33 ± 5.47 vs. 5.39 ± 5.42, P = 0.290), oral corticosteroid use (-117.50 ± 94.38 vs. -115.06 ± 456.85 mg, P = 0.688), fractional exhaled nitric oxide levels (-18.62 ± 24.68 vs. -14.66 ± 45.35 ppb, P = 0.415), sputum eosinophils (-3.40 ± 10.60 vs. -14.48 ± 24.01 %, P = 0.065), blood eosinophils (-36.47 ± 517.02 vs. -363.22 ± 1294.59, P = 0.013), and exacerbation frequency (-3.07 ± 4.42 vs. -3.19 ± 5.11, P = 0.943). The odds ratio for exacerbation and time-to-first exacerbation showed no significant difference after full adjustments, and subgroup analysis according to biologic type was also showed similar results. Conclusions: Biologics treatment response patterns in patients with ACO and asthma were comparable, suggesting that biologics should be actively considered for ACO patients as well.
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Invariant natural-killer T (iNKT) cells play pathogenic roles in allergic asthma in murine models and possibly also humans. While many studies show that the development and functions of innate and adaptive immune cells depend on their metabolic state, the evidence for this in iNKT cells is very limited. It is also not clear whether such metabolic regulation of iNKT cells could participate in their pathogenic activities in asthma. Here, we showed that acetyl-coA-carboxylase 1 (ACC1)-mediated de novo fatty-acid synthesis is required for the survival of iNKT cells and their deleterious functions in allergic asthma. ACC1, which is a key fatty-acid synthesis enzyme, was highly expressed by lung iNKT cells from WT mice that were developing asthma. Cd4-Cre::Acc1fl/fl mice failed to develop OVA-induced and HDM-induced asthma. Moreover, iNKT cell-deficient mice that were reconstituted with ACC1-deficient iNKT cells failed to develop asthma, unlike when WT iNKT cells were transferred. ACC1 deficiency in iNKT cells associated with reduced expression of fatty acid-binding proteins (FABPs) and peroxisome proliferator-activated receptor (PPAR)γ, but increased glycolytic capacity that promoted iNKT-cell death. Furthermore, circulating iNKT cells from allergic-asthma patients expressed higher ACC1 and PPARG levels than the corresponding cells from non-allergic-asthma patients and healthy individuals. Thus, de novo fatty-acid synthesis prevents iNKT-cell death via an ACC1-FABP-PPARγ axis, which contributes to their homeostasis and their pathogenic roles in allergic asthma.
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Asma , Células T Matadoras Naturais , Hipersensibilidade Respiratória , Humanos , Animais , Camundongos , Hipersensibilidade Respiratória/metabolismo , Hipersensibilidade Respiratória/patologia , Asma/patologia , Homeostase , Morte CelularRESUMO
BACKGROUND: In some large to massive rotator cuff tears (RCTs), fatty degeneration (FD) is more severe in the infraspinatus than the supraspinatus muscle, and in such cases, suprascapular neuropathy is highly suspected. Nerve release at the suprascapular notch might alleviate this problem. PURPOSE: To evaluate the effects of the transverse scapular ligament (TSL) release in patients with large to massive RCTs with more severe FD of the infraspinatus than the supraspinatus. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Between September 2017 and January 2022, arthroscopic TSL release with rotator cuff repair was performed in patients with large to massive RCTs and more severe FD of the infraspinatus muscle than the supraspinatus muscle (TSL group). Cuff integrity, FD, and atrophy of cuff muscles were evaluated using preoperative and 1-year postoperative magnetic resonance imaging. In addition, results were compared with those of patients who did not undergo TSL release during arthroscopic large to massive rotator cuff repair (NTSL group). RESULTS: A total of 103 patients-20 in the TSL group and 83 in the NTSL group-were included. Group preoperative characteristics, including tear size and supraspinatus FD, were not significantly different, but infraspinatus FD (TSL vs NTSL; grade, 0-4, 0/0/5/10/5 vs 1/33/42/4/3) and atrophy (grade, 1-3. 3/9/8 vs 56/20/7) differed significantly (P < .001). Healing failure occurred in 13 of 20 (65%) patients in the TSL group and 30 of 83 (36%) patients in the NTSL group, which was a statistically significant difference (P = .019). Postoperatively, infraspinatus FD and atrophy were more severe in the TSL group than in the NTSL group (P < .001), and supraspinatus FD was more severe in the TSL group (P = .029). Seven patients in the TSL group achieved healing, but FD and atrophy of the supraspinatus and the infraspinatus showed no improvement in this group (all, P > .05). CONCLUSION: In patients with more FD in the infraspinatus than the supraspinatus muscle, TSL release appeared to have no benefit for cuff healing or FD reversal in cuff muscles. The possibility of suprascapular nerve entrapment remains in patients with more FD in the infraspinatus than the supraspinatus, and this potential nerve problem is not properly addressed by TSL release alone.
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Lesões do Manguito Rotador , Manguito Rotador , Humanos , Manguito Rotador/cirurgia , Manguito Rotador/patologia , Artroscopia/métodos , Lesões do Manguito Rotador/cirurgia , Lesões do Manguito Rotador/patologia , Atrofia/patologia , Imageamento por Ressonância Magnética , LigamentosRESUMO
Allergic diseases are a major public health problem with increasing prevalence. These immune-mediated diseases are characterized by defective epithelial barriers, which are explained by the epithelial barrier theory and continuously emerging evidence. Environmental exposures (exposome) including global warming, changes and loss of biodiversity, pollution, pathogens, allergens and mites, laundry and dishwasher detergents, surfactants, shampoos, body cleaners and household cleaners, microplastics, nanoparticles, toothpaste, enzymes and emulsifiers in processed foods, and dietary habits are responsible for the mucosal and skin barrier disruption. Exposure to barrier-damaging agents causes epithelial cell injury and barrier damage, colonization of opportunistic pathogens, loss of commensal bacteria, decreased microbiota diversity, bacterial translocation, allergic sensitization, and inflammation in the periepithelial area. Here, we review scientific evidence on the environmental components that impact epithelial barriers and microbiome composition and their influence on asthma and allergic diseases. We also discuss the historical overview of allergic diseases and the evolution of the hygiene hypothesis with theoretical evidence.
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INTRODUCTION: This study aimed to investigate whether low-volume local anesthetic with intravenous dexamethasone can reduce the incidence of diaphragmatic paresis while maintaining the analgesic duration compared with conventional volume of local anesthetic without intravenous dexamethasone when performing ultrasound-guided superior trunk block in patients undergoing arthroscopic shoulder surgery. METHODS: Eighty-four adult patients undergoing arthroscopic shoulder surgery under general anesthesia were randomly assigned to receive ultrasound-guided superior trunk block using 7 mL of 0.5% ropivacaine with 0.15 mg/kg of intravenous dexamethasone (treatment group), or 15 mL of 0.5% ropivacaine with intravenous normal saline (control group). The co-primary outcomes were (1) the duration of analgesia (time between block completion and onset of surgical pain with a Numeric Rating Scale pain score of 4 or higher), which was compared against a non-inferiority margin of 3 hours, and (2) the incidence of diaphragmatic paresis evaluated using M-mode ultrasonography in the post-anesthesia care unit. RESULTS: The mean duration of analgesia was 12.4 (6.8) and 11.2 (4.6) hours in the treatment and control groups, respectively (mean difference: -1.2 hours; 95% CI -3.8 to 1.3]; p for non-inferiority<0.001), meeting the non-inferiority criteria. The incidence of diaphragmatic paresis was 45.2% and 85.4% in the treatment and control groups, respectively (relative risk: 0.53; 97.5% CI 0.35 to 0.80; p<0.001). CONCLUSIONS: Superior trunk block using low-volume local anesthetic with intravenous dexamethasone can reduce the incidence of diaphragmatic paresis while providing non-inferior analgesic duration compared with the conventional volume of local anesthetic in patients undergoing arthroscopic shoulder surgery. TRIAL REGISTRATION NUMBER: Clinical Research Information Service of Republic of Korea Registry (KCT0005998).
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BACKGROUND: For severe anterior glenoid bone loss due to recurrent shoulder instability, the Latarjet procedure offers a dynamic sling effect in addition to bone augmentation. Yet, it heavily alters the surrounding anatomy, while fixation and graft union issues are also common. PURPOSE/HYPOTHESIS: The purpose of this study was to compare a novel printed 3-dimensional (3D) partial glenoid arthroplasty (PGA) implant with the classic Latarjet procedure. It was hypothesized that by replicating the original glenoid geometry and preserving soft tissue anatomy, PGA may better reproduce normal joint kinematics. In addition, the locking screw construct may offer stronger fixation. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 14 matched cadaveric shoulders were tested. The PGA implant was 3D printed in titanium based on preoperative computed tomography. The intact, 25% anterior glenoid bone loss, and postoperative states were tested in the scapular and coronal planes. The following parameters were measured: articular surface area and stepoff, rotational range of motion and the humeral head apex position during rotation, and load and linear stiffness at 25% anterior translation and at 2-mm construct displacement. RESULTS: The baseline dimensions of the glenoid articular surface were comparable between the groups. The articular surface area after PGA was significantly larger (P = .006) with less articular stepoff (P = .030). PGA better approximated the intact state's external (P = .006) and total (P = .019) rotational range of motion in the scapular plane. The course of the humeral head apex after PGA better followed that of the intact state (P < .001). Resistance against anterior translation after PGA was not significantly different compared with after the Latarjet procedure. Greater linear stiffness (P = .031) and loading (P = .002) at 2-mm construct displacement were demonstrated in the PGA group. CONCLUSION: In addressing anterior glenoid bone loss, PGA better approximated intact glenohumeral joint kinematics compared with the Latarjet procedure with less articular stepoff in a cadaveric model. PGA was comparable in resisting anterior translation while being significantly stronger against loading at 2-mm construct displacement. Further clinical studies are warranted to validate this novel procedure. CLINICAL RELEVANCE: A 3D-printed PGA implant may offer an alternative treatment option for severe glenoid bone loss due to shoulder instability, overcoming the previous drawbacks of the Latarjet procedure, including altered kinematics, fixation failure, and hardware issues.