摘要
Recent advancements in organoid technology have led to a vigorous movement towards utilizing it as a substitute for animal experiments. Organoid technology offers versatile applications, particularly in toxicity testing of pharmaceuticals or chemical substances. However, for the practical use in toxicity testing, minimal guidance is required to ensure reliability and relevance. This paper aims to provide minimal guidelines for practical uses of kidney organoids derived from human pluripotent stem cells as a toxicity evaluation model in vitro.
摘要
Korean Renal Data System (KORDS) is a nationwide end-stage renal disease (ESRD) registry database operated by the Korean Society of Nephrology (KSN). Diabetes mellitus is currently the leading cause of ESRD in Korea; this article provides an update on the trends and characteristics of diabetic ESRD patients. The KORDS Committee of KSN collects data on dialysis centers and patients through an online registry program. Here, we analyzed the status and trends in characteristics of diabetic chronic kidney disease stage 5D (CKD 5D) patients using data from 2001 to 2021. In 2021, the dialysis adequacy of hemodialysis (HD) was lower in diabetic CKD 5D patients than in nondiabetic CKD 5D patients, while that of peritoneal dialysis (PD) was similar. Diabetic CKD 5D patients had a higher proportion of cardiac and vascular diseases and were more frequently admitted to hospitals than nondiabetic CKD 5D patients, and the leading cause of death was cardiac disease. From 2001 to 2020, diabetic CKD 5D patients had a higher mortality rate than nondiabetic CKD 5D patients, but in 2021 this trend was reversed. Diabetic PD patients had the highest mortality rate over 20 years. The mortality rate of diabetic HD patients was higher than that of nondiabetic HD patients until 2019 but became lower starting in 2020. There was a decreasing trend in mortality rate in diabetic CKD 5D patients, but cardiac and vascular diseases were still prevalent in diabetic CKD 5D patients with frequent admissions to hospitals. More specialized care is needed to improve the clinical outcomes of diabetic CKD 5D patients.
摘要
With an increasing aging population, the mean age of patients with end-stage kidney disease (ESKD) is globally increasing. However, the current clinical status of elderly patients undergoing hemodialysis (HD) is rarely reported in Korea. The current study analyzed the clinical features and trends of older patients undergoing HD from the Korean Renal Data System (KORDS) database. The patients were divided into three groups according to age: <65 years (the young group), n = 50,591 (35.9%); 65–74 years (the younger-old group), n = 37,525 (26.6%); and ≥75 years (the older-old group), n = 52,856 (37.5%). The proportion of older-old group undergoing HD significantly increased in incidence and decreased in prevalence from 2013 to 2022. The median levels of hemoglobin, serum creatinine, albumin, calcium, phosphorus, and intact parathyroid hormone significantly decreased in the older-old group. The proportions of arteriovenous fistula creation and left forearm placement showed decreased trends with age. Although the utilization of low surface area dialyzers increased with age, the dialysis adequacy, including urea reduction ratio and Kt/V was within acceptable range in the older-old group on HD. Over the past 20 years, the mortality rate in the older-old group has increased, with cardiovascular diseases decreasing and infectious diseases increasing. The incidence of elderly patients undergoing HD has increased over time, but the high mortality of the older-old group needs to be solved. Therefore, it is imperative to develop holistic strategies based on age and individual needs for patients with ESKD.
摘要
Reversible cerebral vasoconstriction syndrome is a condition characterized by transient constriction of cerebral arteries, which can lead to headaches and neurological abnormalities. In a case involving a patient who experienced headaches following a head injury, we present a case where the distinctive feature of thunderclap headache, typical of reversible cerebral vasoconstriction syndrome, was not observed, leading to a misdiagnosis of post-concussion syndrome.
摘要
Kidney organoids derived from human pluripotent stem cells (hPSCs) contain multilineage nephrogenic progenitor cells and can recapitulate the development of the kidney. Kidney organoids derived from hPSCs have the potential to be applied in regenerative medicine as well as renal disease modeling, drug screening, and nephrotoxicity testing. Despite biotechnological advances, individual differences in morphological and growth characteristics among kidney organoids need to be addressed before clinical and commercial application. In this study, we hypothesized that an automated noninvasive method based on deep learning of bright-field images of kidney organoids can predict their differentiation status. Methods: Bright-field images of kidney organoids were collected on day 18 after differentiation. To train convolutional neural networks (CNNs), we utilized a transfer learning approach. CNNs were trained to predict the differentiation of kidney organoids on bright-field images based on the messenger RNA expression of renal tubular epithelial cells as well as podocytes. Results: The best prediction model was DenseNet121 with a total Pearson correlation coefficient score of 0.783 on a test dataset. W classified the kidney organoids into two categories: organoids with above-average gene expression (Positive) and those with below-average gene expression (Negative). Comparing the best-performing CNN with human-based classifiers, the CNN algorithm had a receiver operating characteristic-area under the curve (AUC) score of 0.85, while the experts had an AUC score of 0.48. Conclusion: These results confirmed our original hypothesis and demonstrated that our artificial intelligence algorithm can successfully recognize the differentiation status of kidney organoids.
摘要
Background@#In this study, we aimed to compare the effectiveness and adverse reactions of nirmatrelvir/ritonavir and molnupiravir in high-risk outpatients with coronavirus disease 2019 (COVID-19). @*Methods@#This multicenter prospective observational study evaluated the rate of hospitalization, death, and adverse events within 28 days of oral antiviral agent prescription (molnupiravir, n = 240; nirmatrelvir/ritonavir, n = 240) to 480 nonhospitalized adult patients with COVID-19 from August 2, 2022 to March 31, 2023. @*Results@#Patients receiving molnupiravir had a higher prevalence of comorbidities (85.8% vs. 70.4%; P < 0.001) and a higher Charlson comorbidity index (2.8 ± 1.4 vs. 2.5 ± 1.5; P = 0.009) than those receiving nirmatrelvir/ritonavir. Three patients required hospitalization (nirmatrelvir/ritonavir group, n = 1 [0.4%]; molnupiravir group, n = 2 [0.8%]; P = 1.000). Nirmatrelvir/ritonavir was associated with a higher risk of adverse events than molnupiravir (odds ratio [OR], 1.96; 95% confidence interval [CI], 1.27–3.03), especially for patients aged 65 years and older (OR, 3.04; 95% CI, 1.71–5.39). The severity of adverse events in both groups was mild to moderate and improved after discontinuation of medication. In the molnupiravir group, age ≥ 65 years (OR, 0.43 95% CI, 0.22–0.86) and appropriate vaccination (OR, 0.37; 95% CI, 0.15–0.91) reduced the occurrence of adverse events. @*Conclusion@#The rates of hospitalization and death were low and not significantly different between high-risk patients who received either nirmatrelvir/ritonavir or molnupiravir. Although adverse events were more frequent with nirmatrelvir/ritonavir than with molnupiravir, none were severe. Nirmatrelvir/ritonavir can be safely used to treat COVID-19, while molnupiravir could be considered as an alternative treatment option for high-risk groups.
摘要
A 74-year-old female patient was diagnosed with unilateral vocal fold paralysis without any brain lesions, but with a history of influenza infection 1 week ago. No significant manifestations were observed in the oral phase in the Video Fluoroscopic Swallowing Study (VFSS). However, during swallowing aspiration, 50% of the residue after swallowing was measured as semisolid, and aspiration was observed when swallowing in the liquid form. The Penetration Aspiration Scale (PAS) score was 6 points, and the Functional Dysphagia Scale (FDS) was 46 points.Vocal-fold adduction was performed by injecting hyaluronic acid. Four days after the vocal fold injection, VFSS showed no aspiration during the swallowing of semisolids. Moreover, compared to the initial test, 10% of the residue measured after swallowing semisolids was decreased. No aspiration was observed when swallowing the liquid.Scores obtained for the Penetration Aspiration Scale (PAS) and the Functional Dysphagia Scale (FDS) were 4 and 26, respectively. Taken together, our results indicate that in a situation where upper respiratory infections are increasing due to the COVID-19 pandemic, hyaluronic acid injections have the potential to improve dysphagia in patients with unilateral vocal fold paralysis due to a viral infection.
摘要
Tearing of the acetabular labrum is a common cause of chronic hip pain. MR arthrography (MRA) of the hip is the imaging procedure of choice for the evaluation of acetabular labrum. Familiarity with the various imaging findings of MRA of the hip allows recognition of normal variants and differentiation from true pathologic conditions. This article comprehensively reviews the technical aspects and interpretation of MRA of the hip. The appearances of normal and abnormal labra in MRA are discussed. Potential pitfalls in labral tear interpretation, such as sulci around the hip, normal variants of the labrum and plicae, and osseocartilaginous and soft tissue lesions identified on MRA of the hip are also described.
摘要
Background@#Fabry disease is a rare X-linked genetic lysosomal disorder caused by mutations in the GLA gene encoding alpha-galactosidase A. Despite some data showing that profibrotic and proinflammatory cytokines and oxidative stress could be involved in Fabry disease-related renal injury, the pathogenic link between metabolic derangement within cells and renal injury remains unclear. @*Methods@#Renal fibrosis was triggered by unilateral ureteral obstruction (UUO) in mice with Fabry disease to investigate the pathogenic mechanism leading to fibrosis in diseased kidneys. @*Results@#Compared to kidneys of wild-type mice, lamellar inclusion bodies were recognized in proximal tubules of mice with Fabry disease. Sirius red and trichrome staining revealed significantly increased fibrosis in all UUO kidneys, though it was more prominent in obstructed Fabry kidneys. Renal messenger RNA levels of inflammatory cytokines and profibrotic factors were increased in all UUO kidneys compared to sham-operated kidneys but were not significantly different between UUO control and UUO Fabry mice. Protein levels of Nox2, Nox4, NQO1, catalase, SOD1, SOD2, and Nrf2 were not significantly different between UUO control and UUO Fabry kidneys, while the protein contents of LC3-II and LC3-I and expression of Beclin1 were significantly decreased in UUO kidneys of Fabry disease mouse models compared with wild-type mice. Notably, TUNEL-positive cells were elevated in obstructed kidneys of Fabry disease mice compared to wild-type control and UUO mice. @*Conclusion@#These findings suggest that impaired autophagy and enhanced apoptosis are probable mechanisms involved in enhanced renal fibrosis under the stimulus of UUO in Fabry disease.
摘要
Background@#The Korean Society of Nephrology (KSN) has maintained a nationwide end-stage renal disease (ESRD) registry data from Korean Renal Data System (KORDS) since 1985, as the representative registry of ESRD patients in Korea. This review is aimed to update the status of domestic ESRD and to provide evidence on the direction of dialysis therapy. @*Methods@#The KORDS Committee of KSN has collected data on dialysis centers and patients through an online registry program, and the data from 1986 to 2019 were analyzed. @*Results@#The incidence and prevalence of ESRD patients in Korea are increasing. The ESRD population numbered more than 100,000 in 2019, doubling during the 10 years since 2010. The proportion of diabetes mellitus as a major cause of ESRD seems to have reached a plateau. The increasing number of elderly dialysis patients is a constant trend, with more than half for the proportion of patients older than 65 years old in 2019. All-cause mortality decreased for the last approximately 20 years, regardless of sex, age, and cause of ESRD. The 5-year patient survival rate in both hemodialysis and peritoneal dialysis increased from 2001 to 2013. Since 2013, the patient survival rates in peritoneal dialysis were similar to those in hemodialysis. Cardiovascular complications were the leading cause of death in ESRD patients. @*Conclusions@#The incidence and prevalence of Korean ESRD patients have increased over time, although patient survival has also steadily increased. The establishment of a surveillance method to address the major cause of mortality in ESRD patients will help improve outcomes.
摘要
Background/Aims@#Studies on the effectiveness of public health measures to prevent respiratory virus transmission in real-world settings are lacking. We investigated the effectiveness of universal mask use and adherence to other personal preventive measures on the changing viral respiratory infection patterns during the coronavirus disease 2019 (COVID-19) pandemic. @*Methods@#Data were extracted from the South Korean National Respiratory Virus Sentinel Surveillance System. During the COVID-19 pandemic, a cross-sectional survey on adherence to personal preventive measures was conducted. Additionally, the number of subway passengers was analyzed to estimate physical distancing compliance. @*Results@#During the pandemic, adherence to personal preventive measures significantly increased, particularly indoors and on public transportation. Respiratory virus trends were compared based on laboratory surveillance data of 47,675 patients with acute respiratory infections (2016 to 2020). The 2019 to 2020 influenza epidemic ended within 3 weeks, from the epidemic peak to the epidemic end, quickly ending the inf luenza season; with a 1.8- to 2.5-fold faster decline than in previous seasons. Previously, the overall respiratory virus positivity rate remained high after the influenza seasons had ended (47.7% to 69.9%). During the COVID-19 pandemic, this positive rate, 26.5%, was significantly lower than those in previous years. Hospital-based surveillance showed a decreased number of hospitalized patients with acute viral respiratory illnesses. @*Conclusions@#This study suggests that high compliance to the use of personal preventive measures in public might reduce the incidence of all respiratory virus infections and its hospitalization rates, with no additional quarantine, isolation, or contact screening.
摘要
Tearing of the acetabular labrum is a common cause of chronic hip pain. MR arthrography (MRA) of the hip is the imaging procedure of choice for the evaluation of acetabular labrum. Familiarity with the various imaging findings of MRA of the hip allows recognition of normal variants and differentiation from true pathologic conditions. This article comprehensively reviews the technical aspects and interpretation of MRA of the hip. The appearances of normal and abnormal labra in MRA are discussed. Potential pitfalls in labral tear interpretation, such as sulci around the hip, normal variants of the labrum and plicae, and osseocartilaginous and soft tissue lesions identified on MRA of the hip are also described.
摘要
Background@#Fabry disease is a rare X-linked genetic lysosomal disorder caused by mutations in the GLA gene encoding alpha-galactosidase A. Despite some data showing that profibrotic and proinflammatory cytokines and oxidative stress could be involved in Fabry disease-related renal injury, the pathogenic link between metabolic derangement within cells and renal injury remains unclear. @*Methods@#Renal fibrosis was triggered by unilateral ureteral obstruction (UUO) in mice with Fabry disease to investigate the pathogenic mechanism leading to fibrosis in diseased kidneys. @*Results@#Compared to kidneys of wild-type mice, lamellar inclusion bodies were recognized in proximal tubules of mice with Fabry disease. Sirius red and trichrome staining revealed significantly increased fibrosis in all UUO kidneys, though it was more prominent in obstructed Fabry kidneys. Renal messenger RNA levels of inflammatory cytokines and profibrotic factors were increased in all UUO kidneys compared to sham-operated kidneys but were not significantly different between UUO control and UUO Fabry mice. Protein levels of Nox2, Nox4, NQO1, catalase, SOD1, SOD2, and Nrf2 were not significantly different between UUO control and UUO Fabry kidneys, while the protein contents of LC3-II and LC3-I and expression of Beclin1 were significantly decreased in UUO kidneys of Fabry disease mouse models compared with wild-type mice. Notably, TUNEL-positive cells were elevated in obstructed kidneys of Fabry disease mice compared to wild-type control and UUO mice. @*Conclusion@#These findings suggest that impaired autophagy and enhanced apoptosis are probable mechanisms involved in enhanced renal fibrosis under the stimulus of UUO in Fabry disease.
摘要
Background@#The Korean Society of Nephrology (KSN) has maintained a nationwide end-stage renal disease (ESRD) registry data from Korean Renal Data System (KORDS) since 1985, as the representative registry of ESRD patients in Korea. This review is aimed to update the status of domestic ESRD and to provide evidence on the direction of dialysis therapy. @*Methods@#The KORDS Committee of KSN has collected data on dialysis centers and patients through an online registry program, and the data from 1986 to 2019 were analyzed. @*Results@#The incidence and prevalence of ESRD patients in Korea are increasing. The ESRD population numbered more than 100,000 in 2019, doubling during the 10 years since 2010. The proportion of diabetes mellitus as a major cause of ESRD seems to have reached a plateau. The increasing number of elderly dialysis patients is a constant trend, with more than half for the proportion of patients older than 65 years old in 2019. All-cause mortality decreased for the last approximately 20 years, regardless of sex, age, and cause of ESRD. The 5-year patient survival rate in both hemodialysis and peritoneal dialysis increased from 2001 to 2013. Since 2013, the patient survival rates in peritoneal dialysis were similar to those in hemodialysis. Cardiovascular complications were the leading cause of death in ESRD patients. @*Conclusions@#The incidence and prevalence of Korean ESRD patients have increased over time, although patient survival has also steadily increased. The establishment of a surveillance method to address the major cause of mortality in ESRD patients will help improve outcomes.
摘要
Background/Aims@#Studies on the effectiveness of public health measures to prevent respiratory virus transmission in real-world settings are lacking. We investigated the effectiveness of universal mask use and adherence to other personal preventive measures on the changing viral respiratory infection patterns during the coronavirus disease 2019 (COVID-19) pandemic. @*Methods@#Data were extracted from the South Korean National Respiratory Virus Sentinel Surveillance System. During the COVID-19 pandemic, a cross-sectional survey on adherence to personal preventive measures was conducted. Additionally, the number of subway passengers was analyzed to estimate physical distancing compliance. @*Results@#During the pandemic, adherence to personal preventive measures significantly increased, particularly indoors and on public transportation. Respiratory virus trends were compared based on laboratory surveillance data of 47,675 patients with acute respiratory infections (2016 to 2020). The 2019 to 2020 influenza epidemic ended within 3 weeks, from the epidemic peak to the epidemic end, quickly ending the inf luenza season; with a 1.8- to 2.5-fold faster decline than in previous seasons. Previously, the overall respiratory virus positivity rate remained high after the influenza seasons had ended (47.7% to 69.9%). During the COVID-19 pandemic, this positive rate, 26.5%, was significantly lower than those in previous years. Hospital-based surveillance showed a decreased number of hospitalized patients with acute viral respiratory illnesses. @*Conclusions@#This study suggests that high compliance to the use of personal preventive measures in public might reduce the incidence of all respiratory virus infections and its hospitalization rates, with no additional quarantine, isolation, or contact screening.
摘要
Background@#Pyomyositis (PM) is a serious soft tissue infection and despite its clinical importance, previous studies have not been able to fully determine the clinical characteristics and microbial epidemiology of PM in Korea, which we therefore aimed to investigate. @*Materials and Methods@#We retrospectively identified 140 adult patients diagnosed with PM from 13 general hospitals between January 2012 and December 2015. We analyzed the clinical and microbial characteristics of community-onset PM and compared them with communityacquired (CA) and healthcare-associated (HCA) PM. @*Results@#One hundred eleven organisms were isolated from 96 (68.6%) patients with PM.Staphylococcus aureus (38 patients) was the most common pathogen, followed by streptococci (24 patients), and enteric Gram-negative organisms (27 patients). Methicillin-resistant S.aureus (MRSA) was identified in four (2.9%) patients and in-hospital mortality reached 8.6% (12/140). Enterococci isolates were identified in the HCA PM subgroup only The proportion of MRSA isolates was not comparable between CA and HCA PM subgroups. In the 83 patients with PM infected by monomicrobial pathogens, isolates of Gram-negative organisms were more commonly found in HCA PM subgroup than in CA PM subgroup (47.6% [10/21] of patients with HCA PM vs. 20.7% [12/58] of patients with CA PM; P = 0.01). @*Conclusion@#Gram-positive cocci such as S. aureus and streptococci were dominant etiologies in community-onset PM, whereas MRSA appears to an uncommon causative organism of PM in Korea. Enteric Gram-negative organisms should also be considered as major etiologies, especially in HCA PM patient population in Korea.
摘要
Background@#Pyomyositis (PM) is a serious soft tissue infection and despite its clinical importance, previous studies have not been able to fully determine the clinical characteristics and microbial epidemiology of PM in Korea, which we therefore aimed to investigate. @*Materials and Methods@#We retrospectively identified 140 adult patients diagnosed with PM from 13 general hospitals between January 2012 and December 2015. We analyzed the clinical and microbial characteristics of community-onset PM and compared them with communityacquired (CA) and healthcare-associated (HCA) PM. @*Results@#One hundred eleven organisms were isolated from 96 (68.6%) patients with PM.Staphylococcus aureus (38 patients) was the most common pathogen, followed by streptococci (24 patients), and enteric Gram-negative organisms (27 patients). Methicillin-resistant S.aureus (MRSA) was identified in four (2.9%) patients and in-hospital mortality reached 8.6% (12/140). Enterococci isolates were identified in the HCA PM subgroup only The proportion of MRSA isolates was not comparable between CA and HCA PM subgroups. In the 83 patients with PM infected by monomicrobial pathogens, isolates of Gram-negative organisms were more commonly found in HCA PM subgroup than in CA PM subgroup (47.6% [10/21] of patients with HCA PM vs. 20.7% [12/58] of patients with CA PM; P = 0.01). @*Conclusion@#Gram-positive cocci such as S. aureus and streptococci were dominant etiologies in community-onset PM, whereas MRSA appears to an uncommon causative organism of PM in Korea. Enteric Gram-negative organisms should also be considered as major etiologies, especially in HCA PM patient population in Korea.
摘要
Background/Aims@#Tacrolimus has been used as an immunosuppressive agent in organ transplantation. Despite the therapeutic benefits, tacrolimus’s use is limited due to its nephrotoxicity. To reduce tacrolimus nephrotoxicity, effective humanized experimental models may be helpful. Here, we modeled tacrolimus nephrotoxicity using kidney organoids derived from human inducible pluripotent stem cells (iPSCs) in vitro. @*Methods@#Kidney organoids were differentiated from the CMC11 iPSC cell line, re-seeded in 96-well plates, and treated with tacrolimus at doses of 0, 30, or 60 μM for 24 hours. This in vitro model was compared to a mouse model of tacrolimus nephrotoxicity and the associated mechanisms were investigated. @*Results@#The size of the kidney organoids and cell viability decreased in dose-dependent manners after treatment with tacrolimus. The number of tubular cells decreased with a loss of polarity, similar to the effects seen in mouse tacrolimus nephrotoxicity. Ultrastructural analysis showed numerous vacuoles in the proximal tubular cells of the kidney organoids treated with tacrolimus. Tacrolimus treatment induced oxidative stress and mitochondrial dysfunction, and autophagic activity was enhanced in the kidney organoids. Rapamycin, an autophagy inducer, accelerated cell death in the kidney organoid model of tacrolimus nephrotoxicity, which was attenuated by treatment with 3-methyladenine, an autophagy inhibitor. These findings indicate that the augmentation of autophagy by rapamycin treatment accelerated tacrolimus nephrotoxicity. @*Conclusions@#Our data suggest that human kidney organoids are an effective in vitro model of tacrolimus nephrotoxicity and that autophagy plays a critical role in tacrolimus nephrotoxicity.
摘要
Dysphagia is a relatively rare symptom of neurovascular compression of the lower cranial nerve (CN). Many case reviews of neurovascular compression required surgical treatment to improve the neurological symptoms. This report presents a 75-year-old female patient who complained of dysphagia due to neurovascular compression of CNs IX-XI at the left side after the onset period. The symptom was improved by treating with balloon swallowing rehabilitation (BSR). In a video fluoroscopic swallowing study (VFSS), no significant manifestations were observed in the oral phase. On the other hand, profuse post-swallow residue decreased pharyngeal propulsion were observed without aspiration or penetration during the semisolid portion of the swallowing test. To reduce the pharyngeal remnant and improve pharyngeal propulsion, the BSR protocol was performed and the patient recovered quickly.Follow-up VFSS showed improvement in the post-swallow residue from 42.6 to 7.3%. After discharge, the patient could resume a normal diet without complications. Based on this observed result, it is advantageous to consider the option of a prescribed rehabilitation program over surgical treatment.