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2.
J Rural Med ; 19(3): 150-157, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38975038

RESUMEN

Objective: Rapid bone development in growing children causes excessive tension in the lower extremities' muscles and tendons, leading to reduced flexibility and increased musculoskeletal disorder risk. Further, lack of exercise causes obesity. Therefore, we created a stretching exercise protocol to prevent musculoskeletal disorders in elementary school (middle and upper grades) children during their growth period, when rapid bone development begins. Patients and Methods: We examined the effects on pain, injury, and flexibility. Fifty-three (boys: 34, girls: 19) students in grades 3-5 (ages 9-11) performed the stretching exercises at school thrice a week for one year, and we compared the results before and a year after the intervention. Results: A three-minute stretching exercise routine achieved an intensity of 4.6-4.9 metabolic equivalents (METs; equivalent to brisk walking). Obesity (P=1.000), flexibility problems (inability to bend forward [P=0.754] or squat problems [P=1.000]), bone/joint pain (P=1.000), and injury (P=1.000) did not significantly increase. Conclusion: Stretching exercises during the growth period may help prevent childhood musculoskeletal disorders, obesity, and flexibility loss.

3.
Sci Rep ; 14(1): 15975, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38987260

RESUMEN

Psoriasis is a chronic inflammatory disease that sometimes necessitates therapeutic intervention with biologics. Autoantibody production during treatment with tumor necrosis factor (TNF) inhibitors is a recognized phenomenon, however, the production of autoantibodies associated with antiphospholipid syndrome (APS) has not been comprehensively evaluated in patients with psoriasis. This study was conducted to assess the prevalence of APS-associated autoantibodies in patients with psoriasis treated with different biologics and to investigate the potential associations between autoantibody production and clinical or serological parameters. Patients with psoriasis undergoing biologics treatments were enrolled in this study, and were categorized based on the type of biologics administered, TNF, interleukin (IL)-17, or IL-23 inhibitors. Clinical and serological data were collected and analyzed in conjunction with data on APS autoantibodies. TNF inhibitors were associated with a higher frequency of APS autoantibodies compared to IL-17 and IL-23 inhibitors. Notably, the presence of APS autoantibodies correlated with concurrent arthritis and higher disease severity at treatment initiation in patients treated with TNF inhibitors. Elevated Psoriasis Area and Severity Index scores and anti-nuclear antibody titers higher than × 320 were predictors of APS autoantibody production. Despite the higher autoantibody rates, clinical symptoms of APS were absent in these patients. This study provides the first comprehensive evidence of an increased frequency of APS autoantibodies associated with TNF inhibitor treatment in patients with psoriasis. The observed association between APS autoantibody positivity and TNF inhibitor treatment or clinical parameters suggests a potential immunomodulatory interplay between autoimmunity and inflammation in the pathogenesis of psoriasis.


Asunto(s)
Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , Productos Biológicos , Psoriasis , Humanos , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Femenino , Masculino , Persona de Mediana Edad , Productos Biológicos/uso terapéutico , Productos Biológicos/efectos adversos , Adulto , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Antifosfolípidos/inmunología , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/tratamiento farmacológico , Interleucina-17/antagonistas & inhibidores , Interleucina-17/inmunología , Interleucina-23/inmunología , Interleucina-23/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/inmunología , Prevalencia , Anciano , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Índice de Severidad de la Enfermedad , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/efectos adversos
4.
J Dermatol ; 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38711287

RESUMEN

Atopic dermatitis (AD) is often characterized by chronic skin changes of dermal fibrosis, typically regulated by inflammatory and angiogenic factors. However, the significance of angiogenesis inhibitory factors in the development of AD is poorly understood. The present study investigated the potential role of an angiogenesis inhibitory factor, vasohibin-1 (VASH1), in AD by evaluating serum and skin VASH1 levels and their correlation with clinical features. The results showed that VASH1 expression levels in both the serum and skin of patients with AD were significantly elevated compared to healthy controls. Immunohistochemical staining of AD skin showed increased VASH1 expression in dermal vascular endothelial cells. Notably, there was a significant correlation between serum VASH1 levels and disease duration as well as VASH1 and vascular endothelial growth factor A expression levels in the skin tissue of patients with AD. These results may suggest a pathogenesis of increased angiogenesis and associated elevated inhibitory processes accompanying inflammation in the chronic phase of AD.

5.
J Med Internet Res ; 26: e54645, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38657229

RESUMEN

BACKGROUND: Understanding patient preference regarding taking tablet or capsule formulations plays a pivotal role in treatment efficacy and adherence. Therefore, these preferences should be taken into account when designing formulations and prescriptions. OBJECTIVE: This study investigates the factors affecting patient preference in patients who have difficulties swallowing large tablets or capsules and aims to identify appropriate sizes for tablets and capsules. METHODS: A robust data set was developed based on a questionnaire survey conducted from December 1, 2022, to December 7, 2022, using the harmo smartphone app operated by harmo Co, Ltd. The data set included patient input regarding their tablet and capsule preferences, personal health records (including dispensing history), and drug formulation information (available from package inserts). Based on the medication formulation information, 6 indices were set for each of the tablets or capsules that were considered difficult to swallow owing to their large size and concomitant tablets or capsules (used as controls). Receiver operating characteristic (ROC) analysis was used to evaluate the performance of each index. The index demonstrating the highest area under the curve of the ROC was selected as the best index to determine the tablet or capsule size that leads to swallowing difficulties. From the generated ROCs, the point with the highest discriminative performance that maximized the Youden index was identified, and the optimal threshold for each index was calculated. Multivariate logistic regression analysis was performed to identify the risk factors contributing to difficulty in swallowing oversized tablets or capsules. Additionally, decision tree analysis was performed to estimate the combined risk from several factors, using risk factors that were significant in the multivariate logistic regression analysis. RESULTS: This study analyzed 147 large tablets or capsules and 624 control tablets or capsules. The "long diameter + short diameter + thickness" index (with a 21.5 mm threshold) was identified as the best indicator for causing swallowing difficulties in patients. The multivariate logistic regression analysis (including 132 patients with swallowing difficulties and 1283 patients without) results identified the following contributory risk factors: aged <50 years (odds ratio [OR] 1.59, 95% CI 1.03-2.44), female (OR 2.54, 95% CI 1.70-3.78), dysphagia (OR 3.54, 95% CI 2.22-5.65), and taking large tablets or capsules (OR 9.74, 95% CI 5.19-18.29). The decision tree analysis results suggested an elevated risk of swallowing difficulties for patients with taking large tablets or capsules. CONCLUSIONS: This study identified the most appropriate index and threshold for indicating that a given tablet or capsule size will cause swallowing difficulties, as well as the contributory risk factors. Although some sampling biases (eg, only including smartphone users) may exist, our results can guide the design of patient-friendly formulations and prescriptions, promoting better medication adherence.


Asunto(s)
Cápsulas , Registros Electrónicos de Salud , Comprimidos , Humanos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Registros de Salud Personal , Trastornos de Deglución , Deglución , Encuestas y Cuestionarios , Prioridad del Paciente/estadística & datos numéricos
6.
Microbiol Resour Announc ; 13(4): e0123523, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38488372

RESUMEN

Paraburkholderia sp. strain 22B1P utilizes 3-chlorobenzoate as a carbon source. Complete genome sequencing of strain 22B1P revealed two chromosomes and two plasmids. The genes involved in the conversion of 3-chlorobenzoate to 3-chlorocatechol and those involved in the conversion of 3-chlorocatechol to 3-oxoadipate were located on chromosomes 2 and 1, respectively.

7.
Dig Endosc ; 36(3): 360-369, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37253160

RESUMEN

OBJECTIVES: Endoscopic management of unresectable hilar malignant biliary obstruction (HMBO) is technically challenging, and effectiveness of stent-in-stent using large-cell, metal stents was reported. A new, large-cell stent with a 6F tapered delivery system was recently developed. The aim of this study was to compare clinical outcomes of slim-delivery and conventional large-cell stents. METHODS: This was a multicenter retrospective comparative study of stent-in-stent methods using slim-delivery stents (Niti-S Large Cell SR Slim Delivery [LC slim-delivery]) and conventional stents (Niti-S large-cell D-type; LCD) for unresectable HMBO. RESULTS: Eighty-three patients with HMBO were included; 31 LC slim-delivery and 52 LCD. Overall technical and clinical success rates were 100% and 90% in LC slim-delivery group and 98% and 88% in LCD group. Use of the LC slim-delivery was associated with shorter stent placement time in the multiple regression analysis, with a stent placement time of 18 and 23 min in LC slim-delivery and LCD groups, respectively. The early adverse event (AE) rate of LC slim-delivery was 10%, with no cholangitis or cholecystitis as compared to 23% in the LCD group. Recurrent biliary obstruction (RBO) rates and time to RBO were comparable between the two groups: 35% and 44%, and 8.5 and 8.0 months in LC slim-delivery and LCD groups, respectively. The major cause of RBO was tumor ingrowth (82%) in the LC slim-delivery group and sludge (43%) and ingrowth (48%) in LCD group. CONCLUSION: Stent-in-stent methods using LC slim-delivery shortened stent placement time with low early AE rates and comparable time to RBO in patients with HMBO.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangitis , Colestasis , Humanos , Estudios Retrospectivos , Neoplasias de los Conductos Biliares/complicaciones , Neoplasias de los Conductos Biliares/cirugía , Stents/efectos adversos , Colestasis/cirugía , Colestasis/complicaciones , Colangitis/complicaciones , Resultado del Tratamiento
8.
J Intensive Care ; 11(1): 60, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38049894

RESUMEN

BACKGROUND: Japan has four types of intensive care units (ICUs) that are divided into two categories according to the management fee charged per day: ICU management fees 1 and 2 (ICU1/2) (equivalent to high-intensity staffing) and 3 and 4 (ICU3/4) (equivalent to low-intensity staffing). Although ICU1/2 charges a higher rate than ICU3/4, no cost-effectiveness analysis has been performed for ICU1/2. This study evaluated the clinical outcomes and cost-effectiveness of ICU1/2 compared with those of ICU3/4. METHODS: This retrospective observational study used a nationwide Japanese administrative database to identify patients admitted to ICUs between April 2020 and March 2021 and divided them into the ICU1/2 and ICU3/4 groups. The ICU mortality rates and in-hospital mortality rates were determined, and the incremental cost-effectiveness ratio (ICER) (Japanese Yen (JPY)/QALY), defined as the difference between quality-adjusted life year (QALY) and medical costs, was compared between ICU1/2 and ICU3/4. Data analysis was performed using the Chi-squared test; an ICER of < 5 million JPY/QALY was considered cost-effective. RESULTS: The ICU1/2 group (n = 71,412; 60.7%) had lower ICU mortality rates (ICU 1/2: 2.6% vs. ICU 3/4: 4.3%, p < 0.001) and lower in-hospital mortality rates (ICU 1/2: 6.1% vs. ICU 3/4: 8.9%, p < 0.001) than the ICU3/4 group (n = 46,330; 39.3%). The average cost per patient of ICU1/2 and ICU3/4 was 2,249,270 ± 1,955,953 JPY and 1,682,546 ± 1,588,928 JPY, respectively, with a difference of 566,724. The ICER was 718,659 JPY/QALY, which was below the cost-effectiveness threshold. CONCLUSIONS: ICU1/2 is associated with lower ICU patient mortality than ICU3/4. Treatments under ICU1/2 are more cost-effective than those under ICU3/4, with an ICER of < 5 million JPY/QALY.

9.
J Oncol Pharm Pract ; : 10781552231215427, 2023 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-38043932

RESUMEN

INTRODUCTION: In recent years, most molecular target drugs have been administered orally, as prescribed at ambulatory services in hospitals and at patients' homes. Telephone follow-up is increasingly being used in clinical practice for patients needing additional support post-discharge and for the prevention of hospital readmissions. The purpose of this study was to clarify the clinical benefits of telephone follow-up while administering oral anticancer drugs. METHODS: This was a single-center, observational, retrospective study. We evaluated hepatocellular carcinoma patients who received sorafenib or lenvatinib between March 2010 and February 2018. The primary endpoint was the incidence of adverse events. RESULTS: From the total of 130 patients, 83 patients received telephone follow-up and 47 did not. The incidence of hand-foot skin reactions significantly reduced in patients with telephone follow-up (odds ratio (OR) 3.69, 95% confidence interval (CI) 1.16-11.8, p = 0.020). The median durations (ranges) of adherence to oral chemotherapy were 259 days (15-1730) for the telephone follow-up group and 121 days (14-1105) for the no-telephone follow-up group (p < 0.001). Moreover, the disease control rate was significantly higher in the telephone follow-up group (OR 2.52, 95% CI 1.15-5.53, p = 0.020). CONCLUSIONS: Remote interventions, such as telephone follow-up, are useful means of managing adverse events in patients receiving oral anticancer drugs and can lead to improved treatment results.

10.
Pancreatology ; 23(7): 789-796, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37666733

RESUMEN

BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is widely performed for management of pancreatobiliary diseases; however, post-ERCP pancreatitis (PEP) remains as an unsolved problem. Although various risk factors for PEP have been reported, the prediction of PEP remains controversial. This study aimed to develop a predictive model for PEP. METHODS: Consecutive patients undergoing ERCP for biliary indications at two centers were retrospectively studied. Using data from a training cohort, we utilized a multivariable model to select five variables to construct a nomogram. The predictive model was internally and externally validated. Based on the nomogram, the patients were categorized into low-, moderate-, and high-risk groups. RESULTS: Using the data of 2224 patients in the training cohort, five variables were selected to generate a nomogram: 1) sex, 2) indication for ERCP, 3) difficult cannulation, 4) guidewire insertion into the pancreatic duct, and 5) endoscopic sphincterotomy or sphincteroplasty. The most significant risk factor was endoscopic papillary balloon dilation such as endoscopic sphincterotomy or sphincteroplasty. The bias-corrected concordance index was 0.72 in the training cohort and 0.72 in the validation cohort. Calibration curves for both cohorts demonstrated good agreement between the predicted and observed frequencies of the actual outcome. In the validation cohort, PEP developed in 5.0% and 14% of patients in the moderate- and high-risk groups, respectively. CONCLUSIONS: We successfully developed a good predictive model for PEP. The prevention of PEP in high risk patients should be investigated further.


Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica , Pancreatitis , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Estudios Retrospectivos , Nomogramas , Cateterismo , Pancreatitis/epidemiología , Pancreatitis/etiología , Pancreatitis/prevención & control , Factores de Riesgo
11.
J Clin Med ; 12(8)2023 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-37109382

RESUMEN

Systemic inflammation plays a central role in the pathophysiology of psoriasis. This study examined accessible systemic inflammatory markers in patients with psoriasis vulgaris and psoriatic arthritis. We aimed to evaluate their association with psoriasis severity, the presence of arthritis, and drug continuation rates. The findings revealed that neutrophil, monocyte, and platelet count, neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, systemic inflammation response index, systemic immune/inflammation index (SII), and CRP were positively correlated with Psoriasis Area and Severity Index scores. Patients presenting with higher platelet/lymphocyte ratio (PLR) or CRP values were more likely to be diagnosed with psoriatic arthritis than with psoriasis vulgaris in the multivariate regression analysis. Importantly, patients with higher pretreatment neutrophil or platelet count, PLR, and SII were associated with lower treatment continuation rates of conventional systemic agents. Higher pretreatment scores of systemic inflammatory markers did not affect treatment retention rates of biologics. These findings suggest that several accessible systemic inflammatory markers may effectively assess underlying systemic inflammation and may provide an indication for a therapeutic approach in patients with psoriasis vulgaris and psoriatic arthritis.

12.
Dig Endosc ; 35(1): 111-121, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35916499

RESUMEN

OBJECTIVES: Covered self-expandable metal stent (cSEMS) for gastric outlet obstruction (GOO) has been developed to overcome tumor ingrowth but is prone to be associated with an increased risk of migration. Clinical impact of the novel large-bore cSEMS for malignant GOO remains unclear. METHODS: A total of 117 patients undergoing endoscopic cSEMS placement for malignant GOO were enrolled in this multicenter retrospective study. Technical and clinical success, adverse events, recurrent GOO, and survival after stent placement were compared between 24 mm-cSEMS (n = 49) and 20 mm-cSEMS (n = 68). RESULTS: Patient characteristics were well-balanced and thus similar survival was observed between the two groups (136 days vs. 89 days, P = 0.60). Technical success rate of 100% and clinical success rate of 96% were achieved both in 24 mm-cSEMS and 20 mm-cSEMS, respectively. The median cumulative time to recurrent GOO was significantly longer in 24 mm-cSEMS than in 20 mm-cSEMS (380 days vs. 138 days, P = 0.01). The incidence of adverse events and recurrent GOO was comparable: 12% vs. 15% (P = 0.91), and 16% vs. 31% (P = 0.11); however, no stent migration was observed in 24 mm-cSEMS. In a subgroup analysis, the superiority of 24 mm-cSEMS to 20 mm-cSEMS was demonstrated in extrinsic cancers (380 days vs. 121 days, P = 0.01) but not in intrinsic cancers (151 days vs. not reached, P = 0.47). CONCLUSIONS: The 24 mm-cSEMS may improve time to recurrent GOO with ensuring acceptable safety in patients with malignant GOO.


Asunto(s)
Obstrucción de la Salida Gástrica , Stents Metálicos Autoexpandibles , Neoplasias Gástricas , Humanos , Estudios Retrospectivos , Stents Metálicos Autoexpandibles/efectos adversos , Stents/efectos adversos , Obstrucción de la Salida Gástrica/diagnóstico , Obstrucción de la Salida Gástrica/etiología , Obstrucción de la Salida Gástrica/cirugía , Neoplasias Gástricas/patología , Cuidados Paliativos , Resultado del Tratamiento
13.
JGH Open ; 7(12): 869-874, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38162840

RESUMEN

Background and Aim: Recently, the use of various endoscopic procedures performed under X-ray fluoroscopy guidance has increased. With the popularization of such procedures, diagnostic reference levels (DRLs) have been widely accepted as the global standard for various procedures with ionizing radiation. The Radiation Exposure from Gastrointestinal Fluoroscopic Procedures (REX-GI) study aimed to prospectively collect actual radiation exposure (RE) data and establish DRLs in gastrointestinal endoscopy units. In this post hoc analysis of the REX-GI study, we established DRLs for each disease site by analyzing cases of gastrointestinal enteral metallic stent placement. Methods: The REX-GI study was a multicenter, prospective observational study conducted to collect actual RE data during gastrointestinal enteral metallic stent placement. To establish DRL values for three disease sites, namely the esophagus, gastroduodenum, and colon, we examined fluoroscopy time (FT; min), number of X-ray images, air kerma at the patient entrance reference point (K a,r; mGy), and the air kerma-area product (P KA; Gy cm2) during enteral metallic stent placement. Results: Five-hundred and twenty-three stenting procedures were performed. The DRL values of FT (min) and the number of X-ray images for the esophagus/gastroduodenum/colon were 9/16/18 min and 9/15/11 min, respectively. Furthermore, the DRL values of K a,r and P KA for each disease site were 43.3/120/124 mGy and 10.3/36.6/48.4 Gy cm2, respectively. Among the procedures, esophageal stents were significantly associated with the lowest values (P < 0.001). Conclusion: The characteristics of RE vary according to disease site among gastrointestinal enteral metallic stent placements. Thus, it is desirable to set DRL values based on the disease site.

14.
Front Immunol ; 13: 1013382, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36311716

RESUMEN

Bullous pemphigoid (BP) is an autoimmune disease characterized by autoantibody-mediated activation of immune cells and subepidermal blister formation. Excess amounts of extracellular DNA are produced in BP, however, it remains unclear how extracellular DNA contributes to BP pathogenesis. Here we show a possible mechanism by which interleukin (IL)-26 binds to extracellular DNA released from neutrophils and eosinophils to support DNA sensing. Patients with BP exhibited high circulating levels of IL-26, forming IL-26-DNA complexes in the upper dermis and inside the blisters. IL-26-DNA complexes played a dual role in regulating local immunity and blister formation. First, they enhanced the production of inflammatory cytokines in monocytes and neutrophils. Second, and importantly, the complexes augmented the production and activity of proteases from co-cultured monocytes and neutrophils, which induced BP180 cleavage in keratinocytes and dermal-epidermal separation in a modified human cryosection model. Collectively, we propose a model in which IL-26 and extracellular DNA synergistically act on immune cells to enhance autoantibody-driven local immune responses and protease-mediated fragility of dermal-epidermal junction in BP.


Asunto(s)
Penfigoide Ampolloso , Humanos , Autoanticuerpos , Vesícula/etiología , ADN , Inflamación/complicaciones , Interleucinas
15.
J Dermatol ; 49(11): 1124-1130, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35821652

RESUMEN

In recent years, circulating cell-free DNA (cfDNA) has received a great attention as a biomarker for various cancers. Many reports have shown that serum cfDNA levels are elevated in cancer patients and their levels correlate with prognosis and disease activity. The aim of this study was to measure serum cfDNA levels in patients with cutaneous T-cell lymphoma (CTCL) and to evaluate their correlations with hematological and clinical findings. Serum cfDNA levels in CTCL patients were significantly higher than those in healthy controls, and their levels gradually increased with the progression of the disease stage. Positive correlations were detected between serum cfDNA levels and those of lactate dehydrogenase, thymus and activation-regulated chemokine and soluble IL-2 receptor as well as neutrophil and eosinophil count in peripheral blood and neutrophil-to-lymphocyte ratio. Furthermore, CTCL patients with higher serum cfDNA levels exhibited a significantly worse prognosis. Taken together, these results suggest the potential of cfDNA as a new biomarker reflecting prognosis and disease activity in CTCL. CfDNA levels may serve as an indicator for considering the intensity and timing of subsequent therapeutic intervention.


Asunto(s)
Ácidos Nucleicos Libres de Células , Linfoma Cutáneo de Células T , Micosis Fungoide , Síndrome de Sézary , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/patología , Linfoma Cutáneo de Células T/terapia , Pronóstico , Biomarcadores , Micosis Fungoide/patología , Síndrome de Sézary/patología
16.
Front Mol Biosci ; 9: 840649, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35355508

RESUMEN

The peripheral protein quality control (periQC) system eliminates the conformationally defective cystic fibrosis transmembrane conductance regulator (CFTR), including ∆F508-CFTR, from the plasma membrane (PM) and limits the efficacy of pharmacological therapy for cystic fibrosis (CF). The ubiquitin (Ub) ligase RFFL is responsible for the chaperone-independent ubiquitination and lysosomal degradation of CFTR in the periQC. Here, we report that the Ub ligase RNF34 participates in the CFTR periQC in parallel to RFFL. An in vitro study reveals that RNF34 directly recognizes the CFTR NBD1 and selectively promotes the ubiquitination of unfolded proteins. RNF34 was localized in the cytoplasm and endosomes, where RFFL was equally colocalized. RNF34 ablation increased the PM density as well as the mature form of ∆F508-CFTR rescued at low temperatures. RFFL ablation, with the exception of RNF34 ablation, increased the functional PM expression of ∆F508-CFTR upon a triple combination of CFTR modulators (Trikafta) treatment by inhibiting the K63-linked polyubiquitination. Interestingly, simultaneous ablation of RNF34 and RFFL dramatically increased the functional PM ∆F508-CFTR by inhibiting the ubiquitination in the post-Golgi compartments. The CFTR-NLuc assay demonstrates that simultaneous ablation of RNF34 and RFFL dramatically inhibits the degradation of mature ∆F508-CFTR after Trikafta treatment. Therefore, these results suggest that RNF34 plays a crucial role in the CFTR periQC, especially when there is insufficient RFFL. We propose that simultaneous inhibition of RFFL and RNF34 may improve the efficacy of CFTR modulators.

17.
Lancet Reg Health West Pac ; 20: 100376, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35036979

RESUMEN

BACKGROUND: Diagnostic reference levels (DRLs) are required to optimize medical exposure. However, data on DRLs for interventional fluoroscopic procedures are lacking, especially in gastroenterology. This study aimed to prospectively collect currently used radiation doses and help establish national DRLs for fluoroscopy-guided gastrointestinal procedures in Japan. METHODS: This multicentre, prospective, observational study collected actual radiation dose data from endoscopic retrograde cholangiopancreatography (ERCP), interventional endoscopic ultrasound (EUS), balloon-assisted enteroscopy (BAE), enteral metallic stent placement, and enteral tube placement from May 2019 to December 2020. The study outcomes were fluoroscopy time (FT: min), air kerma at the patient entrance reference point (Ka,r: mGy), air kerma area product (PKA: Gycm2), and radiation dose rate (RDR: mGy/min). Additionally, the basic settings of fluoroscopy equipment and the factors related to each procedure were investigated. This study was registered in the UMIN Clinical Trial Registry (UMIN 000036525). FINDINGS: Overall, 12959 fluoroscopy-guided gastrointestinal procedures were included from 23 hospitals in Japan. For 11162 ERCPs, the median/third quartile values of Ka,r (mGy), PKA (Gycm2), and FT (min) were 69/145 mGy, 16/32 Gycm2, and 11/20 min, respectively. Similarly, these values were 106/219 mGy, 23/41 Gycm2 and 17/27 min for 374 interventional EUSs; 53/104 mGy, 16/32 Gycm2 and 10/15 min for 523 metallic stents; 56/104 mGy, 28/47 Gycm2, and 12/18 min for 599 tube placements; and 35/81 mGy, 16/43 Gycm2 and 7/15 min for 301 BAEs, respectively. For the overall radiation dose rate, the median/third quartile values of RDR were 5.9/9.4 (mGy/min). The RDR values at each institution varied widely. INTERPRETATION: This study reports the current radiation doses of fluoroscopy-guided gastrointestinal procedures expressed as DRL quantities. This will serve as a valuable reference for national DRL values. FUNDING: This work was supported by a clinical research grant from the Japanese Society of Gastroenterology.

18.
Intern Med ; 61(10): 1525-1529, 2022 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-34670898

RESUMEN

A 78-year-old woman presenting with severe acute liver failure was admitted to our hospital. On screening for the etiology of acute liver failure, it was diagnosed as being due to idiopathic hypereosinophilic syndrome (eosinophil count reported as 4766/µL; 33.8% of the white blood cells). Her medical history included marked eosinophilia, as observed six months prior to this admission. Corticosteroid therapy was initiated. During the clinical course, duodenal perforation occurred but was managed promptly by appropriate surgery. A liver biopsy, following the initiation of corticosteroid therapy, revealed degenerating hepatic cells with mild eosinophilic infiltration. With corticosteroid therapy, the liver function improved.


Asunto(s)
Úlcera Duodenal , Síndrome Hipereosinofílico , Fallo Hepático Agudo , Úlcera Péptica Perforada , Corticoesteroides/uso terapéutico , Anciano , Biopsia , Úlcera Duodenal/complicaciones , Femenino , Humanos , Síndrome Hipereosinofílico/complicaciones , Síndrome Hipereosinofílico/diagnóstico , Síndrome Hipereosinofílico/tratamiento farmacológico , Fallo Hepático Agudo/etiología
20.
Int J Clin Pract ; 75(11): e14785, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34480837

RESUMEN

BACKGROUND: Implementation of antimicrobial stewardship programmes improve antimicrobial therapies and thus result in better patient outcomes and safety. The impact of prospective audit and feedback (PAF) is likely dependent on how frequently it is conducted, and how quickly after antibiotic prescription it is initiated. To our knowledge, however, no report has yet investigated the impact of an increase in monitoring frequency per day on PAF strategy. Here, we evaluated the clinical impact of an increase in monitoring frequency per day as a PAF strategy in patients receiving antimicrobial injections. METHODS: We conducted a single-centre, retrospective observational pre-post study to evaluate the impact of increasing the frequency of monitoring from once daily (once daily review group) to twice daily (twice daily review group). Time to intervention and clinical outcomes were compared before and after implementation of twice daily review. RESULTS: Time to intervention for inappropriate antimicrobial therapy was significantly shorter in the twice daily review group than the once daily review group (5.1 ± 6.1 hours vs 29.9 ± 21.5 hours, HR: 4.53, 95% CI: 2.90-7.07, P < .001). The twice daily review group had a significantly lower rate of clinical failure (16.2% vs 38.3%, P = .004) and hepatotoxicity (4.1% vs 15.0%, P = .035) than the once daily review group. CONCLUSIONS: An increase in monitoring frequency from once daily to twice daily significantly shortened the time to intervention for inappropriate antimicrobial therapy, with a concomitant reduction in clinical failure and hepatotoxicity.


Asunto(s)
Antiinfecciosos , Programas de Optimización del Uso de los Antimicrobianos , Antibacterianos/uso terapéutico , Retroalimentación , Humanos , Estudios Prospectivos , Estudios Retrospectivos
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