摘要
Background/Aims@#Pneumocystis jirovecii pneumonia (PJP) is a rare but potentially fatal infection. This study was conducted to investigate the risk factors for PJP in inflammatory bowel disease (IBD) patients. @*Methods@#This nationwide, population-based study was conducted in Korea using claims data.Cases of PJP were identified in patients diagnosed with ulcerative colitis (UC) or Crohn’s disease (CD) between 2010 and 2017, and the clinical data of each patient was analyzed. Dual and triple therapy was defined as the simultaneous prescription of two or three of the following drugs: steroids, calcineurin inhibitors, immunomodulators, and biologics. @*Results@#During the mean follow-up period (4.6±2.3 years), 84 cases of PJP were identified in 39,462 IBD patients (31 CD and 53 UC). For CD patients, only age at diagnosis >40 years (hazard ratio [HR], 6.12; 95% confidence interval [CI], 1.58 to 23.80) was significantly associated with the risk of PJP, whereas in UC patients, diagnoses of diabetes (HR, 2.51; 95% CI, 1.19 to 5.31) and chronic obstructive pulmonary disease (HR, 3.41; 95% CI, 1.78 to 6.52) showed significant associations with PJP risk. Triple therapy increased PJP risk in both UC (HR, 3.90; 95% CI, 1.54 to 9.88) and CD patients (HR, 5.69; 95% CI, 2.32 to 14.48). However, dual therapy increased PJP risk only in UC patients (HR, 2.53; 95% CI, 1.36 to 4.70). Additionally, 23 patients (27%) received intensive care treatment, and 10 (12%) died within 30 days. @*Conclusions@#PJP risk factors differ in CD and UC patients. Considering the potential fatality of PJP, prophylaxis should be considered for at-risk IBD patients
摘要
Background/Aims@#Papillary adenocarcinoma is classified to differentiated-type gastric cancer and is indicated for endoscopic submucosal dissection. However, due to its rare nature, there are limited studies on it. The purpose of this study was to determine the outcome of endoscopic submucosal dissection in patients with papillary-type early gastric cancer and to find the risk factors of lymph node metastasis. @*Methods@#Patients diagnosed with papillary-type early gastric cancer at eight medical centers, who underwent endoscopic submucosal dissection or surgical treatment, were retrospectively reviewed. The clinical results and long-term outcomes of post-endoscopic submucosal dissection were evaluated, and the risk factors of lymph node metastasis in the surgery group were analyzed. @*Results@#One-hundred and seventy-six patients with papillary-type early gastric cancer were enrolled: 44.9% (n=79) in the surgery group and 55.1% (n=97) in the endoscopic submucosal dissection group. As a result of endoscopic submucosal dissection, the en bloc resection and curative resection rates were 91.8% and 86.6%, respectively. The procedure-related complication rate was 4.1%, and local recurrence occurred in 3.1% of patients. Submucosal invasion (odds ratio, 3.735; 95% confidence interval, 1.026 to 12.177; p=0.047) and lymphovascular invasion (odds ratio, 7.636; 95% confidence interval, 1.730 to 22.857; p=0.004) were the risk factors of lymph node metastasis in papillary-type early gastric cancer patients. @*Conclusions@#The clinical results of endoscopic submucosal dissection in papillary-type early gastric cancer were relatively favorable, and endoscopic submucosal dissection is considered safe if appropriate indications are confirmed by considering the risk of lymph node metastasis.
摘要
The cytokine IL-7 plays critical and nonredundant roles in T cell immunity so that the abundance and availability of IL-7 act as key regulatory mechanisms in T cell immunity.Importantly, IL-7 is not produced by T cells themselves but primarily by non-lymphoid lineage stromal cells and epithelial cells that are limited in their numbers. Thus, T cells depend on cell extrinsic IL-7, and the amount of in vivo IL-7 is considered a major factor in maximizing and maintaining the number of T cells in peripheral tissues. Moreover, IL-7 provides metabolic cues and promotes the survival of both naïve and memory T cells. Thus, IL-7 is also essential for the functional fitness of T cells. In this regard, there has been an extensive effort trying to increase the protein abundance of IL-7 in vivo, with the aim to augment T cell immunity and harness T cell functions in anti-tumor responses. Such approaches started under experimental animal models, but they recently culminated into clinical studies, with striking effects in reestablishing T cell immunity in immunocompromised patients, as well as boosting anti-tumor effects. Depending on the design, glycosylation, and the structure of recombinantly engineered IL-7 proteins and their mimetics, recombinant IL-7 molecules have shown dramatic differences in their stability, efficacy, cellular effects, and overall immune functions. The current review is aimed to summarize the past and present efforts in the field that led to clinical trials, and to highlight the therapeutical significance of IL-7 biology as a master regulator of T cell immunity.
摘要
Background@#The severity of gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes. We aimed to generate a risk model for predicting insulin-requiring GDM before pregnancy in Korean women. @*Methods@#A total of 417,210 women who received a health examination within 52 weeks before pregnancy and delivered between 2011 and 2015 were recruited from the Korean National Health Insurance database. The risk prediction model was created using a sample of 70% of the participants, while the remaining 30% were used for internal validation. Risk scores were assigned based on the hazard ratios for each risk factor in the multivariable Cox proportional hazards regression model. Six risk variables were selected, and a risk nomogram was created to estimate the risk of insulin-requiring GDM. @*Results@#A total of 2,891 (0.69%) women developed insulin-requiring GDM. Age, body mass index (BMI), current smoking, fasting blood glucose (FBG), total cholesterol, and γ-glutamyl transferase were significant risk factors for insulin-requiring GDM and were incorporated into the risk model. Among the variables, old age, high BMI, and high FBG level were the main contributors to an increased risk of insulin-requiring GDM. The concordance index of the risk model for predicting insulin-requiring GDM was 0.783 (95% confidence interval, 0.766 to 0.799). The validation cohort’s incidence rates for insulin-requiring GDM were consistent with the risk model’s predictions. @*Conclusion@#A novel risk engine was generated to predict insulin-requiring GDM among Korean women. This model may provide helpful information for identifying high-risk women and enhancing prepregnancy care.
摘要
Objective@#Higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are associated with a lower risk of atrial fibrillation (AF). Statin use might exert confounding effects on the paradoxical associations; however, the relationships that distinguish statin users from non-users have not been thoroughly evaluated. @*Methods@#From the Korean National Health Insurance Database, we included 9,778,014 adults who underwent a health examination in 2009. The levels of TC and LDL-C at the health examination were categorized into quartile values of the total study population.We grouped the study population into statin users and non-users and investigated the associations between TC, LDL-C, and the risk of incident AF. @*Results@#Of the total population, 867,336 (8.9%) were taking statins. During a mean followup of 8.2 years, inverse associations of TC – AF and LDL-C – AF were observed; higher levels of TC and LDL-C were associated with the lower risk of AF in the total population. Overall, statin users showed higher AF incidence rate than non-users, but the inverse associations of TC – AF and LDL-C – AF were consistently observed irrespective of statin usage; adjusted hazard ratio with 95% confidence interval was 0.81 (0.79–0.84) for statin users and 0.81 (0.80–0.83) for non-users in the highest TC quartile, and 0.84 (0.82–0.87) for statin users and 0.85 (0.84–0.86) for non-users in the highest LDL-C quartile (all p<0.001). @*Conclusion@#The paradoxical relationship between lipid levels (TC and LDL-C) and the risk of AF remains consistent in both statin users and non-users.
摘要
Purpose@#We investigated the association between continuous renal replacement therapy (CRRT) and mortality after acute glyphosate or glufosinate intoxication. @*Methods@#The electronic medical records of patients with acute herbicide ingestion who were admitted to the regional emergency center of a metropolitan city in Korea from 3/1/2013 to 2/28/2022 were analyzed and reviewed retrospectively. The case group received CRRT, while the control group did not. In total, 96 patients experienced acute herbicide intoxication in the study period. Baseline characteristics were analyzed and compared between the two groups after propensity score matching. The outcome variable was mortality fitted by a Cox proportional hazard model. @*Results@#After full matching between cases of CRRT use and controls (patients who did not receive CRRT) using propensity scores, 96 patients (27 cases, 69 controls) were analyzed. Propensity matching yielded adequate balance (standardized mean differences <0.25) for all covariates. We fit a Cox proportional hazards model with survival as the outcome and CRRT as a factor, including the matching weights in the estimation. The estimated hazard ratio was 0.41 (95% confidence interval, 0.23–0.76; p=0.0044), indicating that CRRT reduced mortality. @*Conclusion@#In this propensity score-matched analysis, CRRT reduced mortality in patients who visited the hospital with acute glyphosate or glufosinate intoxication. In patients with acute herbicide poisoning with high severity calculated by the APACHE II (Acute Physiology and Chronic Health Evaluation II) score and SOFA (Sequential Organ Failure Assessment) score, CRRT should be actively considered to improve the survival rate.
摘要
An increase in the volume of endoscopic procedures performed in recent times has led to increasing detection rates of asymptomatic gastrointestinal subepithelial tumors. However, accurate diagnosis and risk assessment of these tumors preoperatively is challenging. A 70-year-old man patient visited the emergency department for evaluation of melena. Emergency endoscopy revealed an ulcerated subepithelial tumor (8 cm in size) in the gastric cardia and fundus. Computed tomography and upper endoscopy performed at another hospital 6 months earlier were reviewed; the mass showed a significant increase in size (from 2 cm to 8 cm). The patient underwent surgical resection of the mass and was diagnosed with a high-risk gastrointestinal stromal tumor (GIST). In this article, we describe a rare case of a rapidly growing GIST at a rate significantly greater than commonly reported rates.
摘要
Purpose@#There remains controversy about relationship between obesity and gastric cancer. We aimed to examine the association using obesity-persistence. @*Materials and Methods@#We analyzed a nationwide population-based cohort which underwent health check-up between 2009 and 2012. Among them, those who had annual examinations during the last 5 years were selected. Gastric cancer risk was compared between those without obesity during the 5 years (never-obesity group) and those with obesity diagnosis during the 5 years (non-persistent obesity group; persistent obesity group). @*Results@#Among 2,757,017 individuals, 13,441 developed gastric cancer after median 6.78 years of follow-up. Gastric cancer risk was the highest in persistent obesity group (incidence rate [IR], 0.89/1,000 person-years; hazard ratio [HR], 1.197; 95% confidence interval [CI], 1.117 to 1.284), followed by non-persistent obesity group (IR, 0.83/1,000 person-years; HR, 1.113; 95% CI, 1.056 to 1.172) compared with never-obesity group. In subgroup analysis, this positive relationship was true among those < 65 years old and male. Among heavy-drinkers, the impact of obesity-persistence on the gastric cancer risk far increased (non-persistent obesity: HR, 1.297; 95% CI, 1.094 to 1.538; persistent obesity: HR, 1.351; 95% CI, 1.076 to 1.698). @*Conclusion@#Obesity-persistence is associated with increased risk of gastric cancer in a dose-response manner, especially among male < 65 years old. The risk raising effect was much stronger among heavy-drinkers.
摘要
End-stage renal disease (ESRD) patients on hemodialysis have poor nutritional status and associated problems such as inflammation and sarcopenia. Blood urea nitrogen (BUN) is an important measure of uremic toxins, and urea reduction is a marker of hemodialysis efficacy. However, a low protein diet for lower BUN could aggravate malnutrition in patients, and optimal pre-dialysis BUN is not defined. We investigated the association of pre-dialysis BUN with patients’ comorbidities and the relationship between pre-dialysis BUN and serum albumin as a nutrient marker. Among the 67 patients, the average pre- and post-dialysis BUN were 59.2 and 15.0 mg/dL, respectively, serum creatinine was 10.1 mg/dL, and the average serum albumin was 4.0 g/dL. Patients’ age was negatively correlated with serum creatinine (r=−0.277, p<0.05) and albumin (r=−0.453, p<0.001). Predialysis BUN showed a significant positive correlation with serum albumin (r=0.287, p<0.05) and creatinine (r=0.454, p<0.001). However, the predialysis BUN was not significantly related to diabetes, coronary artery disease, congestive heart failure, or cerebrovascular disease. Hemodialysis patients with high pre-dialysis BUN and high serum creatinine could be regarded as having good nutritional status. The significance of this study lies in the potential utility of pre-dialysis blood urea nitrogen as an indicator of the nutritional status of patients. Liberal protein intake might be recommended to adequately dialyzed patients.
摘要
Purpose@#To investigate the clinical characteristics and treatment outcomes of endogenous endophthalmitis (EE) in patients with a history of long-term oral corticosteroid (LTOC) use. @*Methods@#This study was a retrospective review of the medical records of 17 patients (20 eyes) who were diagnosed and treated for EE from LTOC use from March 2004 to December 2019. @*Results@#The mean age of the patients was 70.0 years, and 58.8% were men. Bilateral involvement was observed in three patients (17.6%). Predisposing medical conditions for steroid use were arthritis (6, 35.3%), renal disease (5, 29.4%), lung disease (5, 29.4%), and dermatologic disease (1, 5.9%). The most common causative agents were Gram-positive organisms (60.0%). All patients were treated with systemic antibiotics and vitreous tapping with intravitreal antibiotics or antifungal injection. Pars plana vitrectomy with intravitreal injection of antibiotics was performed in 11 eyes (55.0%). The initial best-corrected visual acuity (BCVA) of 20 eyes was 1.83 ± 0.79 and final BCVA was 0.70 ± 0.98 (p < 0.001). We analyzed the correlation between final visual acuity and initial visual acuity, causative organisms, sepsis, and vitrectomy. The results indicated a poor visual acuity prognosis for the patient group with sepsis. @*Conclusions@#Our study revealed that LTOCs can induce EE. Gram-positive bacteria were the most common causative organisms of EE from LTOC use. The patient group with sepsis showed a worse visual acuity prognosis than the other groups.
摘要
Background and Objectives@#Antithrombotic therapy after percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF) has changed in recent years with new data from large randomized trials and updates to clinical guidelines. This study aimed to investigate the trends in periprocedural antithrombotic regimens in Korean patients with AF undergoing PCI with non-vitamin K antagonist oral anticoagulants (NOACs). @*Methods@#Using the claims database of the Health Insurance Review and Assessment during 2013–2018, 27,594 patients with AF undergoing PCI were identified. The annual prevalence of PCI and prescriptions of each antithrombotic agent, including antiplatelet agents and oral anticoagulants, within 30 days after PCI were investigated. @*Results@#During 2013–2018, the number of patients with AF undergoing PCI increased up to 1.3-fold (from 3,913 to 5,075 patients per year). After the introduction of NOACs, the proportion of dual antiplatelet therapy (DAPT) decreased from 71.9% to 49.8% but still occupied the largest proportion among antithrombotic regimens. Triple antithrombotic therapy (TAT) use increased from 25.4% to 46.0%, and NOAC has rapidly replaced warfarin as the oral anticoagulant of choice. TAT was preferred to DAPT for patients with CHA2 DS2 -VASc score ≥2. Among various factors, prior intracranial hemorrhage was the most powerful predictor of favoring DAPT use over TAT. @*Conclusion@#Since the introduction of NOACs, the patterns of periprocedural antithrombotic regimens have changed rapidly toward more use of TAT, specifically with NOAC-based regimen. Appropriate stroke prevention with oral anticoagulants is still underutilized in patients with AF undergoing PCI in Korea.
摘要
The emergence of a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has become a significant health concern worldwide. Undoubtedly, a better understanding of the innate and adaptive immune responses against SARS-CoV-2 and its relationship with the coronavirus disease 2019 (COVID-19) pathogenesis will be the sole basis for developing and applying therapeutics. This review will summarize the published results that relate to innate immune responses against infections with human coronaviruses including SARS-CoV-1 and SARS-CoV-2 in both humans and animal models. The topics encompass the innate immune sensing of the virus to the dysregulation of various innate immune cells during infection and disease progression.
摘要
Background and Objectives@#Antithrombotic therapy after percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF) has changed in recent years with new data from large randomized trials and updates to clinical guidelines. This study aimed to investigate the trends in periprocedural antithrombotic regimens in Korean patients with AF undergoing PCI with non-vitamin K antagonist oral anticoagulants (NOACs). @*Methods@#Using the claims database of the Health Insurance Review and Assessment during 2013–2018, 27,594 patients with AF undergoing PCI were identified. The annual prevalence of PCI and prescriptions of each antithrombotic agent, including antiplatelet agents and oral anticoagulants, within 30 days after PCI were investigated. @*Results@#During 2013–2018, the number of patients with AF undergoing PCI increased up to 1.3-fold (from 3,913 to 5,075 patients per year). After the introduction of NOACs, the proportion of dual antiplatelet therapy (DAPT) decreased from 71.9% to 49.8% but still occupied the largest proportion among antithrombotic regimens. Triple antithrombotic therapy (TAT) use increased from 25.4% to 46.0%, and NOAC has rapidly replaced warfarin as the oral anticoagulant of choice. TAT was preferred to DAPT for patients with CHA2 DS2 -VASc score ≥2. Among various factors, prior intracranial hemorrhage was the most powerful predictor of favoring DAPT use over TAT. @*Conclusion@#Since the introduction of NOACs, the patterns of periprocedural antithrombotic regimens have changed rapidly toward more use of TAT, specifically with NOAC-based regimen. Appropriate stroke prevention with oral anticoagulants is still underutilized in patients with AF undergoing PCI in Korea.
摘要
PURPOSE@#Gastrointestinal stromal tumors (GISTs) frequently harbor activating gene mutations in either KIT or platelet-derived growth factor receptor A (PDGFRA) and are highly responsive to several selective tyrosine kinase inhibitors. In this study, a targeted next-generation sequencing (NGS) assay with an Oncomine Focus Assay (OFA) panel was used for the genetic characterization of molecular targets in 30 Korean patients with GIST.@*MATERIALS AND METHODS@#Using the OFA that enables rapid and simultaneous detection of hotspots, single nucleotide variants (SNVs), insertion and deletions (Indels), copy number variants (CNVs), and gene fusions across 52 genes relevant to solid tumors, targeted NGS was performed using genomic DNA extracted from formalin-fixed and paraffin-embedded samples of 30 GISTs.@*RESULTS@#Forty-three hotspot/other likely pathogenic variants (33 SNVs, 8 Indels, and 2 amplifications) in 16 genes were identified in 26 of the 30 GISTs. KIT variants were most frequent (44%, 19/43), followed by 6 variants in PIK3CA, 3 in PDGFRA, 2 each in JAK1 and EGFR, and 1 each in AKT1, ALK, CCND1, CTNNB1, FGFR3, FGFR4, GNA11, GNAQ, JAK3, MET, and SMO. Based on the mutation types, majority of the variants carried missense mutations (60%, 26/43), followed by 8 frameshifts, 6 nonsense, 1 stop-loss, and 2 amplifications.@*CONCLUSIONS@#Our study confirmed the advantage of using targeted NGS with a cancer gene panel to efficiently identify mutations associated with GISTs. These findings may provide a molecular genetic basis for developing new drugs targeting these gene mutations for GIST therapy.
摘要
OBJECTIVES@#Loneliness is associated with negative mental and physical health. However, little is known about the risk factors of loneliness in the Korean elderly living alone. The aim of this study was to examine sociodemographic and social network related risks for loneliness among the elderly living alone.@*METHODS@#This is a cross-sectional study that enrolled 1,091 subjects who are the community-residing elderly living alone. Sociodemographic status, medical condition, cognition, mood disorder and levels of loneliness were collected using a self-administered questionnaire and a specific semi-structured interview conducted by a trained nurse. Descriptive statistics were used to analyze data regarding sociodemographic variable and loneliness. Univariate and Multivariate regression analyses were applied to examine factors associated with loneliness.@*RESULTS@#The mean score of loneliness was 3.8 (SD=1.7). No family contact (standardized β=0.115, p<0.001), no religious attendance (standardized β=0.057, p=0.028), no gathering with friends (standardized β=0.088, p=0.001) and high score of Short for of Geriatric Depression Scale (standardized β=0.502, p<0.001) were significantly associated with high loneliness in the elderly living alone.@*CONCLUSIONS@#Family function, social network and depressive mood could be significant risk factors for high loneliness in the elderly living alone. Public health promotion efforts to reduce loneliness should focus on improving family function, social network and decreasing depression.
摘要
There is considerable overlap in the clinical presentations of apathy and depression. However, differential diagnosis between apathy and other psychiatric conditions, including depression and dementia, is important. In this report, we present the case of a 67-year-old woman with a history of receiving selective serotonin reuptake inhibitor (SSRI) treatment for depression. Differential diagnosis between treatment-resistant depression and SSRI-induced apathy syndrome was required. The symptoms of her apathy syndrome were relieved after the discontinuation of SSRIs and the addition of olanzapine, methylphenidate, and modafinil. Furthermore, we briefly review related literature in this article.
摘要
A full-length translational product of the trophinin gene, KIAA1114, is a distinctive marker of cancer stem cells in human hepatocellular carcinoma, and a mAb, Kiatomab, is specific to KIAA1114 antigen. In this study, we addressed the therapeutic potential of Kiatomab for treating both metastatic and solid tumors in mouse models. Kiatomab recognizes the linear epitope of KIAA1114, which is expressed on cell surfaces of various murine cancer cell lines. Kiatomab treatment induced potent antitumor responses in pulmonary metastasis models. Antitumor activity was mediated by the fragment crystallizable portion of Kiatomab and dependent on the host immune system. The use of Kiatomab alone as an antitumor therapy was ineffective in solid tumor models. However, in combination with cyclophosphamide, or by switching the isotype of the mAb, improved antitumor effects of Kiatomab were observed. These results suggest that Kiatomab can be used as a novel mAb for cancer immunotherapy.
Subject(s)
Animals , Humans , Mice , Carcinoma, Hepatocellular , Cell Line , Cyclophosphamide , Immune System , Immunotherapy , Neoplasm Metastasis , Neoplastic Stem Cells摘要
There is considerable overlap in the clinical presentations of apathy and depression. However, differential diagnosis between apathy and other psychiatric conditions, including depression and dementia, is important. In this report, we present the case of a 67-year-old woman with a history of receiving selective serotonin reuptake inhibitor (SSRI) treatment for depression. Differential diagnosis between treatment-resistant depression and SSRI-induced apathy syndrome was required. The symptoms of her apathy syndrome were relieved after the discontinuation of SSRIs and the addition of olanzapine, methylphenidate, and modafinil. Furthermore, we briefly review related literature in this article.
Subject(s)
Aged , Female , Humans , Apathy , Dementia , Depression , Diagnosis, Differential , Methylphenidate , Serotonin , Selective Serotonin Reuptake Inhibitors摘要
Developing a novel vaccine that can be applied against multiple strains of influenza virus is of utmost importance to human health. Previously, we demonstrated that the intranasal introduction of Fc-fused IL-7 (IL-7-mFc), a long-acting cytokine fusion protein, confers long-lasting prophylaxis against multiple strains of influenza A virus (IAV) by inducing the development of lung-resident memory-like T cells, called T(RM)-like cells. Here, we further investigated the mechanisms of IL-7-mFc-mediated protective immunity to IAVs. First, we found that IL-7-mFc treatment augments the accumulation of pulmonary T cells in 2 ways: recruiting blood circulating T cells into the lung and expanding T cells at the lung parenchyma. Second, the blockade of T cell migration from the lymph nodes (LNs) with FTY720 treatment was not required for mounting the protective immunity to IAV with IL-7-mFc, suggesting a more important role of IL-7 in T cells in the lungs. Third, IL-7-mFc treatment also recruited various innate immune cells into the lungs. Among these cells, plasmacytoid dendritic cells (pDCs) play an important role in IL-7-mFc-mediated protective immunity through reducing the immunopathology and increasing IAV-specific cytotoxic T lymphocyte (CTL) responses. In summary, our results show that intranasal treatment with IL-7-mFc modulates pulmonary immune responses to IAV, affecting both innate and adaptive immune cells.