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Bruton's Tyrosine kinase (BTK) plays a pivotal role as the key mediator in B cell signaling. Recent research has revealed that it is also expressed in cells critical to asthma development, such as T cells, and eosinophils. This study aims to investigate the potential of BTK inhibitor in eosinophilic asthma mouse model. BALB/c mice were sensitized with ovalbumin (OVA) via intraperitoneal injections and followed by OVA nebulizations. The mice were treated with 250 µg/ml or 500 µg/ml of ibrutinib before the second intraperitoneal injection and the first nebulization. Two days after the last OVA challenge, airway hyperresponsiveness (AHR) was assessed with methacholine, and differential cell count in bronchoalveolar lavage fluid (BALF) was performed. The cytokines were measured in BALF, and serum OVA-specific IgE and IgG antibody levels were evaluated by ELISA. The inhibitory effect of ibrutinib was also evaluated in splenic mononuclear cells, mast cells, eosinophils, and T cells in vitro. Treatment with ibrutinib significantly attenuated AHR and airway inflammation, compared to the OVA-induced positive control. The treatment also reduced IL-4, IL-5, IL-13 and IFN-γ cytokine levels and suppressed OVA-specific IgE and IgG production compared to the OVA-induced positive control. Additionally, ibrutinib decreased beta-hexosaminidase release from mast cells, type 2 cytokine productions from mononuclear cells and T cells, and eosinophilic activation markers in vitro. The results of this study suggest that ibrutinib treatment could exert anti-allergic effects by inactivating B cells and other BTK-expressing cells. Further studies are needed to investigate the potential therapeutic effect of ibrutinib on allergic diseases.
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Adenina , Adenina/análogos & derivados , Agammaglobulinemia Tirosina Quinasa , Asma , Citocinas , Modelos Animales de Enfermedad , Eosinófilos , Inmunoglobulina E , Ratones Endogámicos BALB C , Ovalbúmina , Piperidinas , Inhibidores de Proteínas Quinasas , Animales , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Asma/tratamiento farmacológico , Asma/inmunología , Piperidinas/uso terapéutico , Piperidinas/farmacología , Ovalbúmina/inmunología , Adenina/uso terapéutico , Adenina/farmacología , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Citocinas/metabolismo , Eosinófilos/inmunología , Eosinófilos/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Ratones , Pirimidinas/uso terapéutico , Pirimidinas/farmacología , Femenino , Pirazoles/uso terapéutico , Pirazoles/farmacología , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Inmunoglobulina G/sangre , Antiasmáticos/uso terapéutico , Antiasmáticos/farmacología , Células Cultivadas , Humanos , Mastocitos/efectos de los fármacos , Mastocitos/inmunologíaRESUMEN
Objective@#Mental health promotion programs using virtual reality (VR) technology have been developed in various forms. This study aimed to investigate the subjective experience of a VR-assisted mental health promotion program for the community population, which was provided in the form of VR experience on a bus to increase accessibility. @*Methods@#Ninety-six people participated in this study. The relationship between the subjective experience and mental health states such as depression, anxiety, perceived stress, and quality of life was explored. The subjective experience on depression and stress before and after VR program treatment was compared using the Wilcoxon signed-rank test. The satisfaction with the VR-assisted mental health promotion program was examined after using the VR program. @*Results@#The VR-assisted mental health promotion program on a bus significantly improved subjective symptoms such as depression (p=0.036) and perceived stress (p=0.010) among all the participants. Among the high-risk group, this VR program significantly relieved subjective depressive feeling score (p=0.033), and subjective stressful feeling score (p=0.035). In contrast, there were no significant changes in subjective depressive feelings (p=0.182) and subjective stressful feelings (p=0.058) among the healthy group. Seventy-two percent of the participants reported a high level of satisfaction, scoring 80 points or more. @*Conclusion@#The findings of this study suggest that the VR-assisted mental health promotion program may effectively improve the subjective depressive and stressful feelings. The use of VR programs on buses to increase of accessibility for the community could be a useful approach for promoting mental health among the population.
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Diaphragmatic injury (DI) following blunt trauma can cause pulmonary complications and increased duration of ventilator-dependent intensive care unit stay. Herein, we present a 62-year-old female patient with severe trauma who was diagnosed with liver laceration and multiple rib fractures and underwent emergency laparotomy. Extubation was attempted; however, the patient had to be reintubated due to dyspnea. After reintubation, decreased right diaphragmatic excursion was confirmed by ultrasonography and the patient was diagnosed with DI. Surface electromyographic biofeedback was performed during diaphragmatic breathing training to increase the effect of pulmonary rehabilitation. Early diagnosis of DI may be possible using ultrasonography, and the use of surface electromyographic biofeedback is suggested for pulmonary rehabilitation in critically ill trauma patients.
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A 74-year-old female patient, who underwent surgery for a left distal tibiofibular fracture 40 years earlier, visited the hospital with an ankle varus deformity due to malunion. The patient complained of discomfort while walking due to the ankle and hindfoot varus deformity but did not complain of ankle pain. Therefore, correction using supramalleolar osteotomy was planned, and through virtual surgical simulation, it was predicted that a correction angle of 24° and an osteotomy gap open of 12 mm would be necessary. An osteotomy guide and an osteotomy gap block were made using three-dimensional (3D) printing to perform the osteotomy and correct the deformity according to the predicted goal. One year after surgery, it was observed that the ankle varus was corrected according to the surgical simulation, and the patient was able to walk comfortably. Thus, for correction of deformity, virtual surgical simulation and a 3D-printed osteotomy guide can be used to predict the target value for correction. This is useful for increasing the accuracy of correction of the deformity.
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Background@#In Korea, tests for evaluating respiratory muscle strength are based on other countries’ clinical experience or standards, which can lead to subjective evaluations. When evaluating respiratory function based on the standards of other countries, several variables, such as the race and cultures of different countries, make it difficult to apply these standards. The purpose of this study was to propose objective respiratory muscle strength standards and predicted values for healthy Korean adults based on age, height, weight, and muscle strength, by measuring maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and peak cough flow (PCF). @*Methods@#This cross-sectional study analyzed MIP, MEP, and PCF in 360 people, each group comprising 30 adult men and women aged 20–70, diagnosed as healthy after undergoing medical check-ups at a general hospital. Hand grip strength (HGS) and the five times sitto-stand test (FTSST) results were also recorded. Correlations among respiratory muscle strength, participant demographics, and overall muscle strength were evaluated using Pearson’s correlation analysis. The predicted values of respiratory muscle strength were calculated using multiple regression analysis. @*Results@#Respiratory muscle strength differed from the values reported in studies from other countries. In the entire samples, both MIP and MEP had the highest correlations with peak HGS (r= 0.643, r = 0.693; P < 0.05), while PCF had the highest correlation with forced expiratory volume in 1 s (r = 0.753; P < 0.05). Age, body mass index, peak HGS, and FTSST results were independent variables affecting respiratory muscle strength. A predictive equation for respiratory muscle strength was developed using the multiple regression equation developed in this study. @*Conclusion@#Respiratory muscle strength index may differ by country. For more accurate diagnoses, standard values for each country are required. This study presents reference values for Korea, and a formula for estimation is proposed when no respiratory muscle strength measurement equipment is available.Trial Registration: Clinical Research Information Service Identifier: KCT0006778
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Objective@#It is necessary to identify the mental health types of young women considering the importance of the mental health during the peripartum period. This study aimed to classify the mental health types in a community sample of young women with pre-pregnancy, pregnancy, or the postpartum period. @*Methods@#A total of 293 young women during pre-pregnancy, pregnancy, or the postpartum period were included in this study. The clinical characteristics of depression, anxiety, perceived stress, and quality of life were assessed. The clinical characteristics of the subject were classified by cluster analysis and compared by analysis of variance. @*Results@#From the cluster analysis, the subjects were classified into three groups. Cluster 1 showed significantly lower depression and anxiety and higher quality of life than those of cluster 2 and 3. Cluster 2 demonstrated significantly higher depression and anxiety and lower quality of life than those of cluster 3 and 1. Cluster 3 represented the intermediate levels between cluster 2 and 1. @*Conclusion@#This study suggested that young women during pre-pregnancy, pregnancy, or the postpartum period might be in a good mental health group, a high-risk group requiring active monitoring, or a group in need of treatment. By monitoring mental health, the groups with high risk or requiring treatment could be discovered and proper management for prevention or improvement of mental health and quality of life can be provided.
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Lobular capillary hemangioma (LCH) is a rapidly growing benign vascular neoplasm of unknown etiology. LCH usually occurs on the cutaneous and mucosal surfaces, such as gingiva, lips, fingers, and face. LCH was previously called ‘pyogenic granuloma (PG),’ because it was thought to be granulation of tissue occurring in reaction to an infectious etiology despite the fact that it demonstrates no infectious signs in histology or microbiology. Instead, its features seem more like angiomatous lesions rather than granulomatous lesions, so the term ‘LCH’ has been used thereafter. Reports of LCH of hypopharynx have been rare. Here we report a 63-yearold male patient with LCH of hypopharynx with a review of related literature.
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Background@#Several studies support the effectiveness and tolerability of virtual reality (VR) interventions in the psychiatric field. This study aimed to examine changes of cognitive performance in VR-assisted mental health promotion programs and to investigate the difference in performance according to clinical characteristics. @*Methods@#Thirty subjects aged >55 years participated in the study. The clinical characteristics of depression, anxiety, perceived stress, quality of life, and cognition were assessed. Cognitive performance in VR-assisted mental health promotion programs was compared between the clusters classified by clinical characteristics. @*Results@#Cluster analysis classified the subjects into three groups. In Cluster 1, the Module 3 training score was significantly different before and after VR performance. In Cluster 2, significant differences were observed in the Module 1 training score, the Module 2 training score, the Module 2 defense failure score, and the Module 3 training score.In Cluster 3, a significant difference was observed in the Module 3 training score. @*Conclusion@#The results of this study suggest that VR performance might differ according to clinical characteristics. A cognitive training strategy using VR has to be differentially established depending on the characteristics of the community population.
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OBJECTIVES@#Opioids are prescribed to treat moderate to severe pain. We investigated recent trends in opioid (morphine, oxycodone, fentanyl, and hydromorphone) prescriptions using data from the Korean National Health Insurance Service-National Sample Cohort between 2002 and 2015. @*METHODS@#The morphine milligram equivalent (MME) was calculated to standardize the relative potency of opioids. The number (cases) or amount (MME) of annual opioid prescriptions per 10,000 registrants was computed to analyze trends in opioid prescriptions after age standardization. Joinpoint regression analysis was conducted to calculate the annual percentage change and average annual percentage change (AAPC). @*RESULTS@#The number (cases) of prescriptions per 10,000 registrants increased from 0.07 in 2002 to 41.23 in 2015 (AAPC, 76.0%; 95% confidence interval [CI], 61.6 to 91.7). The MME per 10,000 registrants increased from 15.06 in 2002 to 40,727.80 in 2015 (AAPC, 103.0%; 95% CI, 78.2 to 131.3). The highest AAPC of prescriptions and MME per 10,000 registrants were observed in the elderly (60-69 years) and in patients treated at general hospitals. Fentanyl prescriptions increased most rapidly among the 4 opioids. @*CONCLUSIONS@#Consumption of opioids greatly increased in Korea over the 14-year study period.
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Comorbid conditions impact the survival of patients with severe acute kidney injury (AKI) who require continuous renal replacement therapy (CRRT). The weights assigned to comorbidities in predicting survival vary based on type of index, disease, and advances in management of comorbidities. We developed a modified Charlson Comorbidity Index (CCI) for use in patients with AKI requiring CRRT (mCCI-CRRT) and improved the accuracy of risk stratification for mortality. Methods: A total of 828 patients who received CRRT between 2008 and 2013, from three university hospital cohorts was included to develop the comorbidity score. The weights of the comorbidities were recalibrated using a Cox proportional hazards model adjusted for demographic and clinical information. The modified index was validated in a university hospital cohort (n = 919) using the data of patients treated from 2009 to 2015. Results: Weights for dementia, peptic ulcer disease, any tumor, and metastatic solid tumor were used to recalibrate the mCCI-CRRT. Use of these calibrated weights achieved a 35.4% (95% confidence interval [CI], 22.1%–48.1%) higher performance than unadjusted CCI in reclassification based on continuous net reclassification improvement in logistic regression adjusted for age and sex. After additionally adjusting for hemoglobin and albumin, consistent results were found in risk reclassification, which improved by 35.9% (95% CI, 23.3%–48.5%). Conclusion: The mCCI-CRRT stratifies risk of mortality in AKI patients who require CRRT more accurately than does the original CCI, suggesting that it could serve as a preferred index for use in clinical practice.
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Purpose@#There have been few reports on comparison between sunitinib and pazopanib as first-line targeted therapy in Korean metastatic clear cell renal cell carcinoma (ccRCC). We sought to analyze the treatment trends of metastatic ccRCC by comparing the effects and adverse events of sunitinib and pazopanib. @*Materials and Methods@#Data of 357 metastatic RCC patients who received the sunitinib or pazopanib as the first-line targeted therapy from the Daegyeong Oncology Study Group database was obtained and analyzed. Among these patients, patients who only clear cell type was confirmed after needle biopsy or nephrectomy were included, and patients who underwent target therapy for less than 3 months were excluded. @*Results@#Of 251 patients who met the inclusion criteria, sunitinib and pazopanib group were identified in 156 (62%) and 95 patients (38%), respectively. Pazopanib group was older (66 years vs. 61 years, p=0.001) and more symptomatic (65% vs. 52%, p=0.037) and had more patients with Karnofsky performance status <80 (20% vs. 11%, p=0.048) and fewer number of organ metastases (p=0.004) compared to sunitinib group. There was no significant difference in disease control rate (88.5% vs. 87.3%, p=0.744), the median progression-free survival (19 months vs. 15 months, p=0.444) and overall survival (25 months vs. 19 months, p=0.721) between sunitinib and pazopanib. The most common grade 3/4 adverse events with sunitinib and pazopanib were anemia (5%) and hand-foot syndrome (3%), respectively. There was no significant difference between sunitinib and pazopanib in number of patients who experienced grade 3/4 adverse events (15% vs. 11%, p=0.275). However, there were more patients who discontinued treatment due to only adverse events in sunitinib group compared to pazopanib group (12% vs. 3%, p=0.020). @*Conclusions@#In Korean metastatic ccRCC, pazopanib tended to be used in patients with poorer health status compared to sunitinib. Sunitinib and pazopanib had no significant difference in treatment effect and survival, but pazopanib had more tolerable adverse events.
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COVID-19 is caused by the SARS-CoV-2 (SC2) virus and is more prevalent and severe in the elderly and patients with comorbid diseases (CM). Because chitinase 3-like-1 (CHI3L1) is induced during aging and CM, the relationships between CHI3L1 and SC2 were investigated. Here we demonstrate that CHI3L1 is a potent stimulator of the SC2 receptor ACE2 and viral spike protein priming proteases (SPP), that ACE2 and SPP are induced during aging and that anti-CHI3L1, kasugamycin and inhibitors of phosphorylation, abrogate these ACE2- and SPP-inductive events. Human studies also demonstrated that the levels of circulating CHI3L1 are increased in the elderly and patients with CM where they correlate with COVID-19 severity. These studies demonstrate that CHI3L1 is a potent stimulator of ACE2 and SPP; that this induction is a major mechanism contributing to the effects of aging during SC2 infection and that CHI3L1 coopts the CHI3L1 axis to augment SC2 infection. CHI3L1 plays a critical role in the pathogenesis of and is an attractive therapeutic target in COVID-19.
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Objective@#To investigate the anatomical characteristics of the biceps femoris short head (BS) and determine the optimal needle placement for BS examination. @*Methods@#Twenty-one lower limbs were dissected. The distances from the medial and lateral margins of the biceps femoris long head (BL) tendon to the common fibular nerve (CFN) (M_CFN_VD and L_CFN_VD, respectively) and the distance from the lateral margin of the BL tendon to the lateral margin of the BS (L_BS_HD) were measured 5 cm proximal to the tip of the fibular head (P1), four fingerbreadths proximal to the tip of the fibular head (P2), and at the upper apex of the popliteal fossa (P3). @*Results@#The BS was located lateral to the BL tendon. The CFN was located along the medial margin of the BL tendon. The median values were 2.0 (P1), 3.0 (P2), and 0 mm (P3) for M_CFN_VD; and 17.4 (P1), 20.2 (P2), and 21.8 mm (P3) for L_CFN_VD; and 8.1 (P1), 8.8 (P2), and 13.0 mm (P3) for L_BS_VD. @*Conclusion@#The lateral approach to the BL tendon was safer than the medial approach for examining the BS. Amore proximal insertion site around the upper apex of the popliteal fossa was more accurate than the distal insertion site. In this study, we propose a safer and more accurate approach for electromyography of the BS.
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Cervical osteophytes are bone spurs that grow on any part of the cervical spine. Osteophytes in the spine are a normal sign of aging and can be associated with conditions such as degenerative disc diseases, osteoarthritis, spinal stenosis, and others. When cervical osteophytes become large enough, main symptoms can include neck pain, radicular pain, neurological problems, and sometimes dysphagia, as well as hoarseness in rare cases. The authors report a case of left vocal cord palsy in a 75-year-old male patient with a large cervical osteophyte with a left anterior protrusion in the C5/C6 level.
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Purpose: Stroke is an abrupt event that often leaves survivors with long term disabilities, causing role changes, and financial strains on households. The profound impact of stroke on survivors may lead to a decline in quality of life due to the physical, psychological, and social difficulties they experience. Taking Malaysia as an example, this study aimed to explore the impact of stroke on survivors and how health services influence their recovery in low and middle-income countries (LMIC).Method: An ethnographic approach with data obtained primarily through in-depth interviews was used. Twenty-seven participants identified as having suffered a stroke were drawn from a health and demographic surveillance system in Malaysia.Results: The physical and social disruption of the lives of stroke survivors was intensified by the resultant financial constraints placed upon individuals, families and households, compounded by inadequate support from the health, and welfare systems. Despite the disruption to their lives, most participants were, at least in part, able to reestablish their lives through various factors that include a strong family support and active coping strategies.Conclusion: In LMIC, recovery can be shaped by the family unit and through active coping strategies especially those in relation to spirituality.Implications for rehabilitationThe impact of stroke on survivors and lack of specialized stroke care compromise the recovery process and quality of life for stroke survivors in low and middle-income countries.Support from the family and reinforcement of religious coping were judged to successfully aid recovery.Physical and emotional impairments as well as psychosocial wellbeing of survivors in the context of environmental factors need to be addressed.
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Adaptación Psicológica , Personas con Discapacidad , Calidad de Vida , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Países en Desarrollo , Personas con Discapacidad/psicología , Personas con Discapacidad/rehabilitación , Estatus Económico , Femenino , Humanos , Malasia/epidemiología , Masculino , Persona de Mediana Edad , Evaluación de Necesidades , Estrés Psicológico/fisiopatología , Accidente Cerebrovascular/economía , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/psicología , Rehabilitación de Accidente Cerebrovascular/métodos , Rehabilitación de Accidente Cerebrovascular/normasRESUMEN
Purpose@#The aim of this study was to analyze the perioperative complications and oncological outcomes of radical prostatectomy (RP) in patients who underwent multiple prostate biopsies. @*Materials and Methods@#A total of 1,112 patients who underwent RP between January 2009 and April 2016 at 4 different centers were included in this study. We divided these patients into 2 groups: patients who underwent only 1st biopsy, and those who underwent 2nd or more repeated biopsies. The association between the number of prior biopsies and perioperative complications and biochemical recurrence (BCR) was analyzed. @*Results@#Of 1,112 patients, 1,046 patients (94.1%) underwent only 1st biopsy, and 66 (5.9%) underwent 2nd or more repeated biopsies. There were no significant differences in preoperative prostate-specific antigen levels, operation times, blood loss volumes, or hospital stay durations (all p>0.05). Patients who underwent multiple prostate biopsies presented with a localized tumor significantly more often (p<0.05). The Gleason score and rate of positive surgical margins were significantly lower in patients with multiple biopsies (all p<0.05). The Cox proportional hazards model analysis indicated that there was no association between the number of prior prostate biopsies and BCR (p>0.05). Kaplan-Meier curve analysis indicated that BCR-free survival rates between the 2 groups were similar (p>0.05). @*Conclusions@#Multiple prostate biopsies are not associated with an increased risk of perioperative complications, adverse pathological outcomes, or higher rates of BCR in patients who have undergone RP. (Korean J Urol Oncol 2020;18:24-31)
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Genome editing has recently emerged as a powerful tool for generating mutant mice. Small deletions of nucleotides in the target genes are frequently found in CRISPR/Cas9 mediated mutant mice. However, there are very few reports analyzing the phenotypes in small deleted mutant mice generated by CRISPR/Cas9. In this study, we generated a mutant by microinjecting sgRNAs targeting the IL2 receptor γ gene and Cas9 protein, into the cytoplasm of IVF-derived NOD.CB17/Prkdcscid/JKrb (NOD/SCID) mice embryos, and further investigated whether a 2 bp deletion of the IL2 receptor γ gene affects severe deficiency of immune cells as seen in NOD/LtSz-scid IL2 receptor γ−/− (NSG) mice. Our results show that the thymus weight of mutant mice is significantly less than that of NOD/SCID mice, whereas the spleen weight was marginally less. T and B cells in the mutant mice were severely deficient, and NK cells were almost absent. In addition, tumor growth was exceedingly increased in the mutant mice transplanted with HepG2, Raji and A549 cells, but not in nude and NOD/SCID mice. These results suggest that the NOD/SCID mice with deletion of 2 bp in the IL2 receptor γ gene shows same phenotype as NSG mice. Taken together, our data indicates that small deletions by genome editing is sufficient to generate null mutant mice.
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The short release half-life of carbon monoxide (CO) is a major obstacle to the effective therapeutic use of carbon monoxide-releasing molecule-2 (CORM-2). The potential of CORM-2-entrapped ultradeformable liposomes (CORM-2-UDLs) to enhance the release half-life of CO and alleviate skin inflammation was investigated in the present study. CORM-2-UDLs were prepared by using soy phosphatidylcholine to form lipid bilayers and Tween 80 as an edge activator. The deformability of CORM-2-UDLs was measured and compared with that of conventional liposomes by passing formulations through a filter device at a constant pressure. The release profile of CO from CORM-2-UDLs was evaluated by myoglobin assay.
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Femenino , Humanos , Embarazo , Contaminantes Atmosféricos , Contaminación del Aire , Monóxido de Carbono , Estudios de Cohortes , Transferencia de Embrión , Fertilización In Vitro , Técnicas In Vitro , Corea (Geográfico) , Dióxido de Nitrógeno , Material Particulado , Índice de Embarazo , Estudios Retrospectivos , Dióxido de AzufreRESUMEN
Objective@#To determine the patterns of tracheostomy cuff pressure changes with various air inflation amounts in different types of tracheostomy tubes to obtain basic data for appropriately managing longterm tracheostomy. @*Methods@#We performed tracheostomy on a 46-year-old male cadaver. Three types of tracheostomy tubes (single-cuffed, double-cuffed, and adjustable flange), divided into 8 different subtypes based on internal tube diameters and cuff diameters, were inserted into the cadaver. Air was inflated into the cuff, and starting with 1 mL air, the cuff pressure was subsequently measured using a manometer. @*Results@#For the 7.5 mm/14 mm tracheostomy tube, cuff inflation with 3 mL of air yielded a cuff pressure within the recommended range of 20–30 cmH2O. The 7.5 mm/24 mm tracheostomy tube showed adequate cuff pressure at 5 mL of air inflation. Similar values were observed for the 8.0 mm/16 mm and 8.0 mm/27 mm tubes. Double-cuffed tracheostomy cuff pressures (7.5 mm/20 mm and 8.0 mm/20 mm tubes) at 3 mL air inflation had cuff pressures of 18–20 cmH2O at both the proximal and distal sites. For the adjustable flange tracheostomy tube, cuff pressure at 6 mL of cuff air inflation was within the recommended range. Maximal cuff pressure was achieved at inflation with almost 14 mL of air, unlike other tube types. @*Conclusion@#Various types of tracheostomy tubes showed different cuff pressures after inflation. These values might aid in developing guidelines For patients who undergo tracheostomy and are discharged home without cuff pressure manometers, this standard might be helpful to develop guidelines.