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Abstract Background Immune checkpoint therapy (ICT) provides durable responses in select cancer patients, yet resistance remains a significant challenge, prompting the exploration of underlying molecular mechanisms. Tyrosylprotein sulfotransferase-2 (TPST2), known for its role in protein tyrosine O-sulfation, has been suggested to modulate the extracellular protein-protein interactions, but its specific role in cancer immunity remains largely unexplored. Methods To explore tumor cell-intrinsic factors influencing anti-PD1 responsiveness, we conducted a pooled loss-of-function genetic screen in humanized mice engrafted with human immune cells. The responsiveness of cancer cells to interferon-γ (IFNγ) was estimated by evaluating IFNγ-mediated induction of target genes, STAT1 phosphorylation, HLA expression, and cell growth suppression. The sulfotyrosine-modified target gene of TPST2 was identified by co-immunoprecipitation and mass spectrometry. The in vivo effects of TPST2 inhibition were evaluated using mouse syngeneic tumor models and corroborated by bulk and single-cell RNA sequencing analyses. Results Through in vivo genome-wide CRISPR screening, TPST2 loss-of-function emerged as a potential enhancer of anti-PD1 treatment efficacy. TPST2 suppressed IFNγ signaling by sulfating IFNγ receptor 1 at Y397 residue, while its downregulation boosted IFNγ-mediated signaling and antigen presentation. Depletion of TPST2 in cancer cells augmented anti-PD1 antibody efficacy in syngeneic mouse tumor models by enhancing tumor-infiltrating lymphocytes. RNA sequencing data revealed TPST2’s inverse correlation with antigen presentation, and increased TPST2 expression is associated with poor prognosis and altered cancer immunity across cancer types. Conclusions We propose TPST2’s novel role as a suppressor of cancer immunity and advocate for its consideration as a therapeutic target in ICT-based treatments.

Heart transplantation (HTx) outcomes have improved with careful donor selection and management; nonetheless, donor shortages remain a major challenge. Optimizing donor management is crucial for improving donor utility rates and post-HTx outcomes. Brain death leads to various pathophysiological changes that can affect multiple organs, including the heart. Understanding these alterations and corresponding management strategies is key to optimizing the donor organ condition. This review assesses several aspects of these pathophysiological changes, including hemodynamic and endocrinological considerations, and emphasizes special consideration for potential cardiac donors, including serial echocardiographic evaluations for reversible cardiac dysfunction and coronary assessments for donors with risk factors.

Objective We aimed to improve the performance of sleep prediction algorithms by increasing the data amount, adding variables reflecting psychological state, and adjusting the data length.Materials and Methods We used ActiGraph GT3X+® and Galaxy Watch Active2™ to collect physical activity and light exposure data. We collected heart rate variability (HRV) data with the Galaxy Watch. We evaluated the performance of sleep prediction algorithms based on different data sources (wearable devices only, sleep diary only, or both), data lengths (1, 2, or 3 days), and analysis methods. We defined the target outcome, ‘good sleep’, as ≥90% sleep efficiency.Results Among 278 participants who denied having sleep disturbance, we used data including 2136 total days and nights from 230 participants. The performance of the sleep prediction algorithms improved with an increased amount of data and added HRV data. The model with the best performance was the extreme gradient boosting model; XGBoost, using both sources combined data with HRV, and 2-day data (accuracy=.85, area under the curve =.80).Conclusions The results show that the performance of the sleep prediction models improved by increasing the data amount and adding HRV data. Further studies targeting insomnia patients and applied researches on non-pharmacological insomnia treatment are needed.

IntroductionThere have been few studies on predictors of weaning failure from MV in patients with heart failure (HF). We sought to investigate the predictive value of B-lines measured by lung ultrasound (LUS) on the risk of weaning failure from mechanical ventilation (MV) and in-hospital outcomes.MethodsThis was a single-center, prospective observational study that included HF patients who were on invasive MV. LUS was performed immediate before ventilator weaning. A positive LUS exam was defined as the observation of two or more regions that had three or more count of B-lines located bilaterally on the thorax. The primary outcome was early MV weaning failure, defined as re-intubation within 72 h.ResultsA total of 146 consecutive patients (mean age 70 years; 65.8% male) were enrolled. The total count of B-lines was a median of 10 and correlated with NT-pro-BNP level (r2 = 0.132, p

Abstract Background Cardiomyopathy, which is a genetically and phenotypically heterogeneous pathological condition, is associated with increased morbidity and mortality. Genetic diagnosis of cardiomyopathy enables accurate phenotypic classification and optimum patient management and counseling. This study investigated the genetic spectrum of cardiomyopathy and its correlation with the clinical course of the disease. Methods The samples of 72 Korean patients with cardiomyopathy (43 males and 29 females) were subjected to whole-exome sequencing (WES). The familial information and clinical characteristics of the patients were reviewed and analyzed according to their genotypes. Results Dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), left ventricular non-compaction cardiomyopathy, and restrictive cardiomyopathy was detected in 41 (56.9%), 25 (34.7%), 4 (5.6%), and 2 (2.8%) patients, respectively. WES analysis revealed positive results in 37 (51.4%) patients. Subsequent familial testing identified ten additional familial cases. Among DCM cases, 19 (46.3%) patients exhibited positive results, with TTN variants being the most common alteration, followed by LMNA and MYH7 variants. Meanwhile, among HCM cases, 15 (60%) patients exhibited positive results with MYH7 variants being the most common alteration. In six patients with positive results, extracardiac surveillance was warranted based on disease information. The incidence of worse outcomes, such as mortality and life-threatening arrhythmic events, in patients with DCM harboring LMNA variants, was higher than that in patients with DCM harboring TTN or MYH7 variants. Conclusions Diverse genotypes were identified in a substantial proportion of patients with cardiomyopathy. Genetic diagnosis enables personalized disease surveillance and management.

Objectives The Korea Disease Control and Prevention Agency promotes vaccination by regularly providing information on its benefits for reducing the severity of coronavirus disease 2019 (COVID-19). This study aimed to analyze the number of averted severe COVID-19 cases and COVID-19-related deaths by age group and quantify the impact of Republic of Korea’s nationwide vaccination campaign. Methods We analyzed an integrated database from the beginning of the vaccination campaign on February 26, 2021 to October 15, 2022. We estimated the cumulative number of severe cases and COVID-19-related deaths over time by comparing observed and estimated cases among unvaccinated and vaccinated groups using statistical modeling. We compared daily age-adjusted rates of severe cases and deaths in the unvaccinated group to those in the vaccinated group and calculated the susceptible population and proportion of vaccinated people by age. Results There were 23,793 severe cases and 25,441 deaths related to COVID-19. We estimated that 119,579 (95% confidence interval [CI], 118,901–120,257) severe COVID-19 cases and 137,636 (95% CI, 136,909–138,363) COVID-19-related deaths would have occurred if vaccination had not been performed. Therefore, 95,786 (95% CI, 94,659–96,913) severe cases and 112,195 (95% CI, 110,870–113,520) deaths were prevented as a result of the vaccination campaign. Conclusion We found that, if the nationwide COVID-19 vaccination campaign had not been implemented, the number of severe cases and deaths would have been at least 4 times higher. These findings suggest that Republic of Korea’s nationwide vaccination campaign reduced the number of severe cases and COVID-19 deaths.

ABSTRACT The coronavirus disease 2019 pandemic persisted for 3 years and is now transitioning to endemicity. We illustrated the change in group immunity induced by vaccination (monovalent vaccines) and breakthrough infections (BIs) in a healthcare worker (HCW) cohort. Five sampling points were analyzed: before the third dose and 1, 3, 5, and 8 months after the vaccination. The last two points corresponded roughly to 1 and 4 months after omicron BA.1/BA.2 BI. A semi-quantitative anti-spike binding antibody (Sab) assay and plaque reduction neutralization test (PRNT) against circulating variants were conducted. A linear regression model was utilized to deduce correlation equations. Baseline characteristics and antibody titers after the third dose were not different between 106 HCWs with or without BI (54/52). One month after the third dose, BA.1 PRNT increased with wild-type (WT), but 3 months after the third dose, it decreased more rapidly than WT PRNT. After BI, BA.1 PRNT increased robustly and waned slower than WT. A linear equation of waning kinetics was deduced between log10Sab and months, and the slope became gradual after BI. The estimated BA.5 PRNT titers at the beginning of the BA.5 outbreak were significantly higher than the BA.1 PRNT titers of the initial BA.1/BA.2 wave, which might be associated with the smaller size of the BA.5 wave. BA.1/BA.2 BI after the third dose elicited robust and broad neutralizing activity, preferentially maintaining cross-neutralizing longevity against BA.1 and BA.5. The estimated kinetics provide an overview of group immunity through the third vaccination and BA.1/BA.2 BI, correlating with the actual outbreaks. IMPORTANCE This study analyzed changes in group immunity induced by coronavirus disease 2019 (COVID-19) vaccination and BA.1/BA.2 breakthrough infections (BIs) in a healthcare worker cohort. We investigated the longitudinal kinetics of neutralizing antibodies against circulating variants and confirmed that BA.1/BA.2 BIs enhance the magnitude and durability of cross-neutralization against BA.1 and BA.5. Correlation equations between semi-quantitative anti-spike antibody and plaque reduction neutralization test titers were deduced from the measured values using a linear regression model. Based on the equations, group immunity was estimated to last up to 11 months following the third dose of the COVID-19 vaccine. The estimated group immunity suggests that the augmented immunity and flattened waning slope through BI could correlate with the overall outbreak size. Our findings could provide a better understanding to establish public health strategies against future endemicity.

Background: Choosing an appropriate endotracheal tube size during the first attempt is crucial for avoiding unnecessary reintubation. Previous studies on endotracheal tube size in children focused on uncuffed tubes. Following recent studies on pediatric airway anatomy, cuffed endotracheal tubes are increasingly utilized in children. The objective of our study was to develop a new formula for selecting the correctly sized cuffed endotracheal tube for pediatric patients. Materials and Methods: We examined the electronic anesthetic records of 465 pediatric patients who received elective ophthalmic surgery between January 2011 and December 2018. Multiple linear regression was used to identify potential predictors of cuffed endotracheal size among age, weight, height, body mass index, and the presence of underweight, overweight, and obesity. We used repeated-measures ANOVA to assess the difference between the actual and calculated sizes of the endotracheal tube. Results: The derived formula is as follows: Predicted endotracheal tube size (mm) = 3.7 + 0.1 × age (years) + 0.02 × weight (kg) + 0.1 × presence of overweight (0: negative, 1: positive). The coefficient of determination (R2) for the total population was 0.685 and was higher in the overweight group (R2 = 0.763). When compared with the three conventional age-based formulas (Cole’s, Khine’s, and Duracher’s formula), the difference between the actual endotracheal tube size and the endotracheal tube size calculated using Duracher’s formula was the smallest. Conclusions: In choosing the appropriate size of a cuffed endotracheal tube in children, age and body size should be considered.

The oyster shell is a valuable calcium resource; however, its application is limited by its high NaCl content. Therefore, to establish the use of oyster shells as a viable resource, conditional experiments were conducted to select optimum parameters for NaCl removal. For this purpose, we compared leaching methods with batch and sequential procedures, determined the volume of water used for washing, and evaluated the mixing speed. The batch system removed NaCl when washed for >24 h over a shell to water ratio of 1:5. Results from the batch experiments confirmed that washing twice can completely remove NaCl from the shells on a like-for-like basis. Additionally, the efficiency of washing was sequentially evaluated in terms of the number of washing cycles. Compared to batch experiments, continuous washing could remove NaCl in approximately 10 min at a shell to water ratio of 1:4. We found that regardless of the washing methods, the volume of water used for washing is key for enhancing NaCl removal. Consequently, increasing the volume of water used for washing coupled with a proper sorting of fine particles can help enhance the purity of calcium, which will enable the use of oyster shell as an alternate Ca-resource.

It is important for clinicians to perform a continuous comprehensive assessment of the depth of sedation, including the use of processed electroencephalographic monitors and the review of clinical signs. Ketamine is a safe anesthetic and sedative traditionally used in the clinical practice. It possesses analgesic, anti-inflammatory, and antidepressant activities and is used as a therapeutic agent in intractable pain. In this case series, we present a comparison between patient state index (PSI) and bispectral index (BIS) in a sample of eight patients with complex regional pain syndrome undergoing ketamine infusion therapy. Blood pressure, heart rate, respiratory rate, end-tidal carbon dioxide, and oxygen saturation were all noted, as well as the PSI and BIS values. The PSI and BIS readings were not recorded when the artifact was larger than 50%. Four patients (50%) received intravenous midazolam 5 mg when their agitation or movement could not be managed by the clinicians’ verbal instructions. In five patients (62%), 20 min after the ketamine infusion began, deep drowsiness was attained. There are fewer research studies on PSI than there are on BIS. We found that PSI values did not match BIS values. This case series could help clinicians select an appropriate course of action for ketamine sedation in individual patients.

Objectives On November 5, 2021, Pfizer Inc. announced Paxlovid (nirmatrelvir+ritonavir) as a treatment method that could reduce the risk of hospitalization or death for patients with confirmed coronavirus disease 2019 (COVID-19). Methods From February 6, 2022 to April 2, 2022, the incidence of COVID-19 and the effects of treatment with Paxlovid were analyzed in 2,241 patients and workers at 5 long-term care facilities during the outbreak of the Omicron variant of severe acute respiratory syndrome coronavirus 2 in South Korea. Results The rate of severe illness or death in the group given Paxlovid was 51% lower than that of the non-Paxlovid group (adjusted risk ratio [aRR], 0.49; 95% confidence interval [CI], 0.24−0.98). Compared to unvaccinated patients, patients who had completed 3 doses of the vaccine had a 71% reduced rate of severe illness or death (aRR, 0.29; 95% CI, 0.13−0.64) and a 65% reduced death rate (aRR, 0.35; 95% CI, 0.15−0.79). Conclusion Patients given Paxlovid showed a lower rate of severe illness or death and a lower fatality rate than those who did not receive Paxlovid. Patients who received 3 doses of the vaccine had a lower rate of severe illness or death and a lower fatality rate than the unvaccinated group.

Objectives Household contacts of confirmed cases of coronavirus disease 2019 (COVID-19) are exposed to a high risk of viral transmission, and secondary incidence is an important indicator of community transmission. This study analyzed the secondary attack rate and mRNA vaccine effectiveness against transmission (VET) for index cases (patients treated at home) confirmed to be infected with the Delta and Omicron variants. Methods The subjects of the study were 4,450 index cases and 10,382 household contacts. Logistic regression analysis was performed to compare the secondary attack rate by vaccination status, and adjusted relative risk and 95% confidence intervals were identified. Results The secondary attack rate of the Delta variant was 27.3%, while the secondary attack rate of the Omicron variant was 29.8%. For the Delta variant, groups with less than 90 days and more than 90 days after 2 doses of mRNA vaccination both showed a VET of 37%. For the Omicron variant, a 64% VET was found among those with less than 90 days after 2 doses of mRNA vaccination. Conclusion This study provides useful data on the secondary attack rate and VET of mRNA vaccines for household contacts of COVID-19 cases in South Korea.

Abstract Background High glycemic variability (GV) is a poor prognostic marker in cardiovascular diseases. We aimed to investigate the association of GV with all-cause mortality in patients with acute heart failure (HF). Methods The Korean Acute Heart Failure registry enrolled patients hospitalized for acute HF from 2011 to 2014. Blood glucose levels were measured at the time of admission, during hospitalization, and at discharge. We included those who had 3 or more blood glucose measurements in this study. Patients were divided into two groups based on the coefficient of variation (CoV) as an indicator of GV. Among survivors of the index hospitalization, we investigated all-cause mortality at 1 year after discharge. Results The study analyzed 2,617 patients (median age, 72 years; median left-ventricular ejection fraction, 36%; 53% male). During the median follow-up period of 11 months, 583 patients died. Kaplan–Meier curve analysis revealed that high GV (CoV > 21%) was associated with lower cumulative survival (log-rank P

Abstract Aims Increased blood pressure (BP) and decreased heart rate (HR) are signs of stabilization in patients admitted for acute HF. Changes in BP and HR during admission and their correlation with outcomes were assessed in hospitalized patients with heart failure (HF) with reduced ejection fraction (HFrEF). Methods A novel modified reverse shock index (mRSI), defined as the ratio between changes in systolic BP and HR during admission, was devised, and its prognostic value in the early outcomes of acute HF was assessed using the Korean Acute HF registry. Results Among 2697 patients with HFrEF (mean age 65.8 ± 14.9 years, 60.6% males), patients with mRSI ≥1.25 at discharge were significantly younger and were more likely to have de novo HF. An mRSI ≥1.25 was associated with a significantly lower incidence of 60‐day and 180‐day all‐cause mortality [hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.31–0.77; HR 0.62, 95% CI 0.45–0.85, respectively], compared with 1 ≤ mRSI

We studied the effect of booster vaccinations on reducing household transmission of SARS-CoV-2 B.1.1529 (Omicron) variant in a February 2022 sampling of contacts in South Korea. The secondary attack rate was lower for vaccinated versus unvaccinated contacts, and booster vaccination resulted in a lower incidence rate ratio.

Abstract This Korean nationwide, multicenter, noninterventional, prospective cohort study aimed to analyze physician adherence to guideline-recommended therapy for heart failure (HF) with reduced ejection fraction (HFrEF) and its effect on patient-reported outcomes (PROs). Patients diagnosed with or hospitalized for HFrEF within the previous year were enrolled. Treatment adherence was considered optimal when all 3 categories of guideline-recommended medications (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or angiotensin receptor-neprilysin inhibitors; beta-blockers; and mineralocorticoid receptor antagonists) were prescribed and suboptimal when ≤ 2 categories were prescribed. The 36-Item Short Form Survey (SF-36) scores were compared at baseline and 6 months between the 2 groups. Overall, 854 patients from 30 hospitals were included. At baseline, the optimal adherence group comprised 527 patients (61.7%), whereas during follow-up, the optimal and suboptimal adherence groups comprised 462 (54.1%) and 281 (32.9%) patients, respectively. Patients in the suboptimal adherence group were older, with a lower body mass index, and increased comorbidities, including renal dysfunction. SF-36 scores were significantly higher in the optimal adherence group for most domains (P

Abstract Aims In 2021, vericiguat was approved by the US Food and Drug Administration (FDA) and the European Commission (EC) for reducing cardiovascular mortality and heart failure (HF) hospitalizations in patients with HF with reduced ejection fraction (HFrEF) based on the Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) trial. However, there has been no report for characterizing the generalizability of vericiguat to real‐world clinical practice. Methods and results The Korean Acute Heart Failure (KorAHF) registry is a multicentre prospective cohort study. A total of 5625 patients who were admitted for HF decompensation were consecutively enrolled. We excluded the patients without left ventricular ejection fraction (LVEF) quantification, patients with LVEF > 45%, patients with in‐hospital death or urgent heart transplantation, and patients without natriuretic peptide measurement. Among a total of 3014 enrolled patients, there were 21.9% patients with lower systolic blood pressure (SBP) (

Abstract Aims A waiting period of more than 3 months is recommended for patients before undergoing cardiac resynchronization therapy (CRT). However, due to an anticipated high mortality rate, early implementation of CRT might be beneficial for some patients. We aimed to evaluate the rate and the probability of left ventricular (LV) function improvement and their predictors in patients with heart failure (HF) with indications for CRT. Methods and results From March 2011 to February 2014, a total of 5625 hospitalized patients for acute HF were consecutively enrolled in 10 tertiary hospitals. Among them, we analysed 1792 patients (mean age 63.96 ± 15.42 years, female 63.1%) with left ventricular ejection fraction (LVEF) ≤ 35% at the baseline echocardiography and divided them into three groups: 144 with left bundle branch block (LBBB), 136 with wide QRS complexes without LBBB, and 1512 not having these findings (control). We compared and analysed these three groups for improvement of LV function at follow‐up echocardiography. In patients who met CRT indications (patients with LBBB or wide QRS complexes without LBBB), logistic regression was performed to identify risk factors for no improvement of LV. No improvement of LV was defined as LVEF ≤ 35% at follow‐up echocardiography or the composite adverse outcomes: death, heart transplantation, extracorporeal membrane oxygenation, or use of a ventricular assist device before follow‐up echocardiography. A classification tree was established using the binary recursive partitioning method to predict the outcome of patients who met CRT indications. In a median follow‐up of 11 months, LVEF improvement was observed in 24.3%, 15.4%, and 40.5% of patients with LBBB, wide QRS complexes without LBBB, and control, respectively. Patients meeting CRT indications had higher 3 month mortality rates than the control (24.6% vs. 17.7%, P = 0.002). Multivariable logistic regression analysis revealed that large LV end‐systolic dimension [odds ratio (OR) 1.10, 95% confidence interval (CI) 1.05–1.15, P

Abstract Background Patients with diabetes mellitus (DM) have a higher prevalence of heart failure (HF) than those without it. Approximately 40 % of HF patients have DM and they tend to have poorer outcomes than those without DM. This study evaluated the impact of insulin therapy on mortality among acute HF patients. Methods A total of 1740 patients from the Korean Acute Heart Failure registry with DM were included in this study. The risk of all-cause mortality according to insulin therapy was assessed using the Cox proportional hazard models with inverse probability of treatment weighting to balance the clinical characteristics (pretreatment covariates) between the groups. Results DM patients had been treated with either oral hypoglycemic agents (OHAs) alone (n = 620), insulin alone (n = 682), or insulin combined with OHAs (n = 438). The insulin alone group was associated with an increased mortality risk compared with the OHA alone group (HR = 1.41, 95 % CI 1.21–1.66]). Insulin therapy combined with OHAs also showed an increased mortality risk (HR = 1.29, 95 % CI 1.14–1.46) compared with the OHA alone group. Insulin therapy was consistently associated with increased mortality risk, regardless of the left ventricular ejection fraction (LVEF) or HF etiology. A significant increase in mortality was observed in patients with good glycemic control (HbA1c

Abstract Background Little is known about endogenous inhibitors of angiogenic growth factors. In this study, we identified a novel endogenous anti-angiogenic factor expressed in pericytes and clarified its underlying mechanism and clinical significance. Methods Herein, we found Kai1 knockout mice showed significantly enhanced angiogenesis. Then, we investigated the anti-angiogenic roll of Kai1 in vitro and in vivo. Results KAI1 was mainly expressed in pericytes rather than in endothelial cells. It localized at the membrane surface after palmitoylation by zDHHC4 enzyme and induced LIF through the Src/p53 pathway. LIF released from pericytes in turn suppressed angiogenic factors in endothelial cells as well as in pericytes themselves, leading to inhibition of angiogenesis. Interestingly, KAI1 had another mechanism to inhibit angiogenesis: It directly bound to VEGF and PDGF and inhibited activation of their receptors. In the two different in vivo cancer models, KAI1 supplementation significantly inhibited tumor angiogenesis and growth. A peptide derived from the large extracellular loop of KAI1 has been shown to have anti-angiogenic effects to block the progression of breast cancer and retinal neovascularization in vivo. Conclusions KAI1 from PC is a novel molecular regulator that counterbalances the effect of angiogenic factors.

In South Korea, a November 2021 outbreak caused by severe acute respiratory syndrome coronavirus 2 Omicron variant originated from 1 person with an imported case and spread to households, kindergartens, workplaces, restaurants, and hospitals, resulting in 11 clusters within 3 weeks. An epidemiologic curve indicated rapid community transmission of the Omicron variant.

To determine optimal quarantine duration, we evaluated time from exposure to diagnosis for 107 close contacts of severe acute respiratory syndrome coronavirus 2 Omicron variant case-patients. Average time from exposure to diagnosis was 3.7 days; 70% of diagnoses were made on day 5 and 99.1% by day 10, suggesting 10-day quarantine.

Birt–Hogg–Dube (BHD) is a rare genetic disorder characterized by multiple lung cysts, typical skin manifestations, and renal tumors. We prospectively enrolled thirty-one subjects from four South Korean institutions with typical lung cysts, and next-generation sequencing was conducted. We prospectively enrolled thirty-one subjects from four Korean institutions with typical lung cysts. Next-generation sequencing was performed to investigate mutations in the following genes: FLCN, TSC1, TSC2, CFTR, EFEMP2, ELN, FBLN5, LTBP4, and SERPINA1. BHD was diagnosed in 11 of the 31 enrolled subjects (35.5%; FLCN mutations). Notably, we identified three novel mutations (c.1098G>A, c.139G>T, and c.1335del) that have not been previously reported. In addition to FLCN mutations, we also observed mutations in CFTR (16.1%), LTBP4 (9.7%), TSC2 (9.7%), TSC1 (3.2%), ELN (3.2%), and SERPINA1 (3.2%). According to a systematic review of 45 South Korean patients with BHD, the prevalence of pneumothorax (72.7%) was greater in South Korea than in the rest of the world (50.9%; p = 0.003). The prevalence of skin manifestations (13.6%) and renal tumors (9.1%) was lower in Korea than in the rest of the world, at 47.9% [p < 0.001] and 22.5% [p = 0.027], respectively). This study confirmed a significant prediction model for BHD based on age, number of lung cysts (>40), and maximal diameter of lung cysts (>2 cm) regardless of skin manifestations and renal tumors. Importantly, three novel mutations (c.1098G>A, c.139G>T, and c.1335del) were identified. In conclusion, South Korean patients with BHD display characteristics that are different from those observed in patients of other nationalities. Detailed characterization of lung cysts is needed to define BHD, especially in South Korea, even if patients do not present with skin or renal lesions.

Abstract To evaluate the clinical impact of preoperative glycemic status upon oncological and functional outcomes after radical prostatectomy in patients with localized prostate cancer, we analyzed the data of 2664 subjects who underwent radical prostatectomy with preoperative measurement of hemoglobin A1c within 6 months before surgery. The possible association between high hemoglobin A1c (≥ 6.5 ng/dL) and oncological/functional outcomes was evaluated. Among all subjects, 449 (16.9%) were categorized as the high hemoglobin A1c group and 2215 (83.1%) as the low hemoglobin A1c group. High hemoglobin A1c was associated with worse pathological outcomes including extra-capsular extension (HR 1.277, 95% CI 1.000–1.630, p = 0.050) and positive surgical margin (HR 1.302, 95% CI 1.012–1.674, p = 0.040) in multi-variate regression tests. Kaplan–Meier analysis showed statistically shorter biochemical recurrence-free survival in the high hemoglobin A1c group (p

With the emergence and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants, escaping vaccine-induced immunity is a concern. Three vaccination schedules, homologous or heterologous, have been initially applied due to an insufficient supply of vaccines in Korea. We investigated neutralizing activities against Omicron and Delta variants in each schedule. Three schedules using three doses of the BNT162b2 (BNT) or the ChAdOx1 (ChAd) vaccines include ChAd-ChAd-BNT, ChAd-BNT-BNT, and BNT-BNT-BNT. Neutralizing activities were evaluated using plaque-reduction neutralization test (PRNT) against wild type (WT) SARS-CoV-2, Delta variant, and Omicron variant. A total of 170 sera from 75 participants were tested, and the baseline characteristics of participants were not significantly different between groups. After the 2nd vaccine dose, geometric mean titers of PRNT ND50 against WT, Delta, and Omicron were highest after ChAd-BNT vaccination (2,463, 1,097, and 107) followed by BNT-BNT (2,364, 674, and 38) and ChAd-ChAd (449, 163, and 25). After the 3rd dose of BNT, the increase of PRNT ND50 against WT, Delta, and Omicron was most robust in ChAd-ChAd-BNT (4,632, 988, and 260), while the BNT-BNT-BNT group showed the most augmented neutralizing activity against Delta and Omicron variants (2,315 and 628). ChAd-BNT-BNT showed a slight increase of PRNT ND50 against WT, Delta, and Omicron (2,757, 1,279, and 230) compared to the 2nd dose. The results suggest that a 3rd BNT booster dose induced strengthened neutralizing activity against Delta and Omicron variants. The waning of cross-reactive neutralizing antibodies after the 3rd dose and the need for additional boosting should be further investigated.

Background/Aims This study investigated the prognostic power of corrected QT (QTc) interval in patients with acute heart failure (AHF) according to sex. Methods We analyzed multicenter Korean Acute Heart Failure registry with patients with AHF admitted from 2011 to 2014. Among them, we analyzed 4,990 patients who were followed up to 5 years. Regarding QTc interval based on 12 lead electrocardiogram, patients were classified into quartiles according to sex. Results During follow-up with median 43.7 months, 2,243 (44.9%) patients died. The relationship between corrected QT interval and all-cause mortality followed a J-curve relationship. In Kaplan-Meier analysis, both sex had lowest mortality in the second QTc quartile. There were significant prognostic differences between the second and the fourth quartiles in male (log-rank p = 0.002), but not in female (log-rank p = 0.338). After adjusting covariates, the third (hazard ratio [HR], 1.185; 95% confidence interval [CI], 1.001 to 1.404; p = 0.049) and the fourth (HR, 1.404; 95% CI, 1.091 to 1.535; p = 0.003) quartiles demonstrated increased risk of mortality compared to the second quartile in male. In female, however, there was no significant difference across quartiles. QTc interval was associated with 5-year all-cause mortality in J-shape with nadir of 440 to 450 ms in male and 470 to 480 ms in female. Conclusions QTc interval was an independent predictor of overall death in male, but its significance decreased in female. The relationship between QTc interval and all-cause mortality was J-shaped in both sex.

BackgroundRandomized clinical trials of spironolactone showed significant mortality reduction in patients with heart failure with reduced ejection fraction. However, its role in acute heart failure syndrome (AHFS) is largely unknown.AimTo investigate the prescription characteristics, efficacy and safety of spironolactone in real-world patients with AHFS.Methods5,136 AHFS patients who survived to hospital discharge using a nationwide prospective registry in Korea were analyzed. The primary efficacy outcome was 3-year all-cause mortality.ResultsSpironolactone was prescribed in 2,402 (46.8%) at discharge: 26%.ConclusionsAlthough spironolactone was frequently used at lower doses in real-world practice, use of spironolactone significantly reduced 3-year mortality in patients with severely reduced LVEF with acceptable safety profile. However, our findings remain prone to various biases and further prospective randomized controlled studies are needed to confirm these findings.

The goal of this study was to isolate and identify the wild yeast strains in intestine of Othius punctulatus collected in Cheongju-si, Chungcheongbuk-do, Korea and characterize their unrecored yeast strains. We isolated 16 wild yeast strains from 5 intestine samples from Othius punctulatus. The 16 wild yeast strains were included three strains in the genus Aureobasidium, four strains in the genus Cystofilobasidium, one strain in the genus Mrakia, three strains in the genus Naganishia, two strains in the genus Saitozyma, two strains in the genus Sampaiozyma and one strain in the genus Scheffersomyces. Among them Cystofilobasidium capitatum YP53, Cystofilobasidium capitatum YP71, Cystofilobasidium macerans YS620, Cystofilobasidium macerans YS622, Mrakia aquatica YP158 and Scheffersomyces stipitis YI5 were recorded for the first time in Korea. The microbiological characteristics and carbon assimilation of these previously unrecorded yeasts were investigated. Almost all of them were oval-shaped. And, glycerol, L-arabinose, xylitol, and inositol are not utilized.

Purpose: Whether active surveillance (AS) can be safely extended to patients with Gleason score (GS) 3+4 prostate cancer is highly debated. We examined the incidence and predictors of upgrading among patients with GS 3+4 disease. Materials and Methods: The study involved 377 patients with biopsy GS 3+4 who underwent robot-assisted laparoscopic radical prostatectomy (RP) from 2014 to 2018 at a single institution. We analyzed the rate of GS upgrading and used logistic regression to determine the predictors of upgrading. Results: A total of 168 (44.6%) patients with GS 3+4 experienced an upgrade in GS. In multivariable analysis, advanced age, prostate-specific antigen (PSA) level, PSA density (PSAD) and Prostate Imaging-Reporting and Data System version 2 (PI-RADS v2) score were significant predictors of GS upgrading. When structured into a predictive model that included age ≥65 years, PSA ≥7.7 ng/mL, PSAD ≥0.475 ng/mL2 and PI-RADS v2 score 4–5, the probability of GS upgrading ranged from 36.4% to 65.7% when one to four of these factors were included. Conclusions: A substantial proportion of patients with GS 3+4 prostate cancer were upgraded after RP. However, according to our model combining clinical and imaging predictors, patients with a low risk of GS upgrading may be eligible candidates for AS.

The goal of this study was to isolate and characterize the wild yeast strains from the gut of earthworm(Eisenia andrei ). The 19 yeast strains isolated from 5 gut of earthworm samples from Nanji water regeneration center in Goyang-si, Gyeonggi-do, Korea. Among them, 16 strains were recorded and 3 strains, Yarrowia deformans YP242 (=KACC48778), Sporidiobolus pararoseus YP66 (=KCTC27963) and Sporidiobolus pararoseus YI9 (=KACC48948) were recorded for the first time in Korea. The microbiological characteristics of these previously unrecorded yeasts were investigated. All three strains were oval-shaped, convex and smooth. However, they showed some differences in colony color and result of carbon assimilation assays. YP242 was white-colored and assimilated glycerol, L-arabinose and N-acetyl-D-glucosamine as carbon sources. YP66 was red-colored and assimilated D-Saccharose. YI9 was white-colored and positive for 2-keto-D-gluconate assimilation.

Abstract Background Although more than one-third of the patients with acute heart failure (AHF) have diabetes mellitus (DM), it is unclear if DM has an adverse impact on clinical outcomes. This study compared the outcomes in patients hospitalized for AHF stratified by DM and left ventricular ejection fraction (LVEF). Methods The Korean Acute Heart Failure registry prospectively enrolled and followed 5625 patients from March 2011 to February 2019. The primary endpoints were in-hospital and overall all-cause mortality. We evaluated the impact of DM on these endpoints according to HF subtypes and glycemic control. Results During a median follow-up of 3.5 years, there were 235 (4.4%) in-hospital mortalities and 2500 (46.3%) overall mortalities. DM was significantly associated with increased overall mortality after adjusting for potential confounders (adjusted hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.03–1.22). In the subgroup analysis, DM was associated with higher a risk of overall mortality in heart failure with reduced ejection fraction (HFrEF) only (adjusted HR 1.14, 95% CI 1.02–1.27). Inadequate glycemic control (HbA1c ≥ 7.0% within 1 year after discharge) was significantly associated with a higher risk of overall mortality compared with adequate glycemic control (HbA1c

Purpose: The clinical behavior of prostate cancer differs by race and ethnicity; however, data on the Korean population are scarce. We assessed the long-term oncologic outcomes of clinically localized prostate cancer after radical prostatectomy in Korean men. Materials and Methods: We analyzed 786 clinically localized prostate cancer patients who underwent radical prostatectomy, from June 1993 to June 2008. Kaplan–Meier survival curve analysis and log-rank test were used to assess the oncologic outcomes. Results: The mean age of the patients was 64.9±6.6 years. Pelvic lymph node dissection was performed in 373 patients. Pathologic T and N stage cancer with local advancement and invasion were detected by radical prostatectomy in 307 and 22 patients, respectively. In total, 38 patients who underwent adjuvant therapy were excluded from the analysis of progression after biochemical recurrence (BCR), which occurred in 261 men. In total, 219 patients underwent salvage treatment. Local recurrence and distant metastasis occurred in 109 and 42 patients, respectively; 36 patients experienced metastasis with local recurrence. Castration-resistant prostate cancer developed in 22 patients, and overall and disease-specific mortality was noted in 148 and 23 patients, respectively. The median duration from operation to BCR, BCR to metastasis, and metastasis to disease-specific death was 25, 40, and 22 months, respectively. Conclusions: We demonstrated the long-term prognosis of localized prostate cancer after radical prostatectomy among Koreans. Our results differ from those reported in the Western literature, with a lower prevalence of distant metastasis and shorter time to metastasis after BCR.

Purpose: To evaluate the impact of diagnostic ureteroscopy performed before radical nephroureterectomy (RNU) on intravesical recurrence (IVR) in patients with upper tract urothelial carcinoma (UTUC). Materials and Methods: From May 2003 to December 2018, patients who underwent RNU for UTUC were enrolled and divided into two groups according to whether they underwent preoperative ureteroscopy (Pre-U vs. Non-U). We excluded patients who had a history of bladder cancer and did not receive bladder cuff resection during surgery. Perioperative parameters were compared between the two groups by use of t-tests or chi-square tests. Kaplan–Meier and Cox proportional hazards analyses were used to assess the association between Pre-U and IVR. Results: Of the 453 total patients, 226 patients (49.9%, Pre-U group) had received diagnostic ureteroscopy before RNU, and 227 patients (50.1%, Non-U group) had not. IVR occurred in 99 patients (43.8%) in the Pre-U group and 61 patients (26.9%) in the Non-U group (p=0.001). The median time to recurrence was 107 months. The 5-year IVR-free survival rates were 56.2% and 73.1% in the Pre-U and Non-U groups, respectively (log rank test, p

Background The prone position is used for a variety of procedures and surgeries, and hypotension is a commonly encountered complication. Case A 75-year-old obese woman with lumbar spinal stenosis underwent posterior lumbar spinal fusion and posterolateral interbody fusion under general anesthesia. Before the surgery, when she was positioned on a Jackson spinal table in the prone position, sudden severe hypotension and hemodynamic collapse developed. The circulatory collapse was refractory to intravascular volume expansion and administration of inotropes and vasopressors. However, the application of external abdominal support immediately restored hemodynamic stability. The patient successfully underwent the surgery using an external abdominal support, and no post-operative complication was noted, including abdominal compartment syndrome. Conclusions The Jackson spinal table allowed the abdomen to hang freely, providing abdominal decompression while resulting in a severely sagged abdomen. We suspected that the sagging abdomen had pulled the abdominal contents downwards, kinking the inferior vena cava or causing a venous pool in the abdomen, resulting in the obstruction of venous return to the heart.

We evaluated contemporary trends in radical prostatectomy (RP) in men aged >70 years and investigated associations of selected variables with recovery of urinary continence (UC) in two age groups: >70 and ≤ 70 years. A retrospective cohort of 2301 eligible patients attending our institution from 2004 to 2015 was reviewed. Patients were divided into two groups based on age at surgery (>70 years [n = 610] vs 70 years [n = 1691]) and four groups by year of surgery. Over the study period, the proportion of patients aged >70 years gradually increased up to 30.0%, and the rate of robot-assisted RP and neurovascular bundle (NVB) saving increased continually to 80.0% and 67.4% of older patients, respectively. Although the rate of recovery of UC within 12 months (3 months) in patients aged >70 years was lower than that in those aged ≤ 70 years (81.5% [52.6%] vs 88.6% [60.9%], respectively; both P < 0.001), the gap between age groups in the rate of recovery within 12 months narrowed from the second quarter of the study period. Among younger patients, age, robot-assisted RP, prostate volume, membranous urethral length (MUL), and NVB saving were predictors of recovery of UC within 3 or 12 months. In contrast, only age and MUL were predictors of recovery of UC within 3 and 12 months in patients aged >70 years. Therefore, unlike younger patients, only variables (age and MUL), possibly associated with the inherent function of the urinary sphincter, were predictors of recovery of UC in patients aged >70 years.

Purpose: We evaluated the prognostic association of pT2 subclassification with the oncological outcomes in patients with prostate cancer (PCa) who underwent radical prostatectomy (RP) in South Korea. Materials and Methods: We retrospectively reviewed 3,529 patients who underwent RP for pathologically organ-confined PCa between 2003 and 2017 at Seoul National University Bundang Hospital. We analyzed the differences in the rates of biochemical recurrence (BCR), overall survival (OS), and cancer-specific survival (CSS) between pT2 substages. Results: According to the 2002 TNM staging system, 362 (15.3%) and 2,000 patients (84.5%) had T2a (involving one-half or less of a unilateral lobe) and T2c (involving bilateral lobes) diseases. Four patients (0.2%) had T2b (involving more than one-half of a unilateral lobe) disease and none of them developed BCR. The mean follow-up period was 8.4±3.7 years and 175 patients (7.4%) had BCR. On multivariable analysis, pT2 subclassification (pT2a/b vs. pT2c) was not a significant predictor of BCR (p=0.224) or OS (p=0.311). Biochemical disease-free survival (p=0.091), OS (p=0.502), and CSS (p=0.063) showed no significant difference between pT2 substages. Conclusions: Our study revealed that the pT2 subclassification of PCa in Korean males provided no value for predicting BCR, OS, and CSS after RP, which agrees with recently reported results based on the updated 8th version of the American Joint Committee on Cancer (AJCC) TNM staging system.

Abstract is missing (Short communication)

Five types of odor-emitting exhaust gases from medical waste were selected, and their adsorption capacity and desorption efficiency were investigated using activated carbon. The selected gases included polar gases (hydrogen sulfide (H2S) and ammonia (NH3)) and non-polar gases (acetaldehyde (AA), methyl mercaptan (MM), and trimethylamine (TMA))). Commercial activated carbon with a specific surface area of 2276 m2/g was used as the adsorbent. For the removal of odor from medical waste, we investigated: (1) the effective adsorption capacity of a single gas (3 gas concentration and flow rate, and (3) the desorption rate using NH3 gas. The values of the effective adsorption capacity of the single gas were in the following order: H2S < NH3 < AA < MM < TMA, at 0.2, 4.2, 6.3, 6.6, and 35.7 mg/g, respectively. The results indicate that polar gases have a lower effective adsorption capacity than that of non-polar gases, and that the size of the gas molecules and effective adsorption capacity exhibit a proportional relationship. The effective adsorption performance of NH3 gas showed an increasing trend with NH3 concentration. Therefore, securing optimal conditions for adsorption/desorption is imperative for the highly efficient removal of odor from medical waste.

Background: Chest computed tomography (CT) findings are important for identifying Birt–Hogg–Dube (BHD) syndrome. However, the predictive power of classical criteria for chest CT findings is weak. Here, we aimed to identify more specific chest CT findings necessitating genetic examination for FLCN gene mutations. Methods: From June 2016 to December 2017, we prospectively enrolled 21 patients with multiple bilateral and basally located lung cysts on chest CT with no other apparent cause, including cases with and without spontaneous primary pneumothorax. All enrolled patients underwent FLCN mutation testing for diagnosis confirmation. Results: BHD was diagnosed in 10 of 21 enrolled patients (47.6%). There were no differences in clinical features between the BHD and non-BHD groups. Maximal cyst diameter was significantly greater in the BHD group (mean ± standard deviation; 4.1 ± 1.1 cm) than in the non-BHD group (1.6 ± 0.9 cm; p < 0.001). Diversity in cyst size was observed in 100.0% of BHD cases and 18.2% of non-BHD cases (p = 0.001). Morphological diversity was observed in 100.0% of BHD cases and 54.6% of non-BHD cases (p = 0.054). Areas under the receiver operating characteristic curves for predicting FLCN gene mutations were 0.955 and 0.909 for maximal cyst diameter and diversity in size, respectively. The optimal cut-off value for maximal diameter FLCN mutations prediction was 2.1 cm (sensitivity: 99%; specificity: 82%). Conclusions: Reliable chest CT features suggesting the need for FLCN gene mutations screening include variations in cyst size and the presence of cysts > 2.1 cm in diameter, predominantly occurring in the bilateral basal lungs.

Background/Aims It is unknown whether different β-blockers (BBs) have variable effects on long-term survival of patients with heart failure with reduced ejection fraction (HFrEF). This study compares the effects of two BBs, carvedilol and bisoprolol, on survival in patients with HFrEF. Methods The Korean Acute Heart Failure (KorAHF) registry is a prospective multicenter cohort that includes 5,625 patients who were hospitalized for acute heart failure (AHF). We selected 3,016 patients with HFrEF and divided this study population into two groups: BB at discharge (n = 1,707) or no BB at discharge (n = 1,309). Among patients with BB at discharge, subgroups were formed based on carvedilol prescription (n = 831), or bisoprolol prescription (n = 553). Propensity score matching analysis was performed. Results Among patients who were prescribed a BB at discharge, 60.5% received carvedilol and 32.7% received bisoprolol. There was a significant reduction in allcause mortality in those patients with HFrEF prescribed a BB at discharge compared to those who were not (BB vs. no BB, 26.1% vs. 40.8%; hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.52 to 0.67; p < 0.001). However, there was no significant difference in the rate of all-cause mortality between those receiving different types of BB (carvedilol vs. bisoprolol, 27.5% vs. 23.5%; HR, 1.21; 95% CI, 0.99 to 1.47; p = 0.07). Similar results were observed after propensity score matching analysis (508 pairs, 26.2% vs. 23.8%; HR, 1.10; 95% CI, 0.86 to 1.40; p = 0.47). Conclusions In the treatment of AHF with reduced EF after hospitalization, mortality benefits of carvedilol and bisoprolol were comparable.

Background Development of chemotherapeutics for the treatment of advanced hepatocellular carcinoma (HCC) has been lagging. Screening of candidate therapeutic agents by using patient-derived preclinical models may facilitate drug discovery for HCC patients. Methods Four primary cultured HCC cells from surgically resected tumor tissues and six HCC cell lines were used for high-throughput screening of 252 drugs from the Prestwick Chemical Library. The efficacy and mechanisms of action of the candidate anti-cancer drug were analyzed via cell viability, cell cycle assays, and western blotting. Results Guanabenz acetate, which has been used as an antihypertensive drug, was screened as a candidate anti-cancer agent for HCC through a drug sensitivity assay by using the primary cultured HCC cells and HCC cell lines. Guanabenz acetate reduced HCC cell viability through apoptosis and autophagy. This occurred via inhibition of growth arrest and DNA damage-inducible protein 34, increased phosphorylation of eukaryotic initiation factor 2α, increased activating transcription factor 4, and cell cycle arrest. Conclusions Guanabenz acetate induces endoplasmic reticulum stress–related cell death in HCC and may be repositioned as an anti-cancer therapeutic agent for HCC patients.

Abstract Background The aim of this study is to fabricate drug-eluting gastrointestinal (GI) stent using reactive oxygen species (ROS)-sensitive nanofiber mats for treatment of cholangiocarcinoma (CCA) cell. A ROS-producing agent, piperlongumine (PL)-incorporated nanofiber mats were investigated for drug-eluting stent (DES) application. Methods Selenocystamine-conjugated methoxy poly(ethylene glycol) (MePEG) was conjugated with poly(L-lactide) (PLA) to produce block copolymer (LEse block copolymer). Various ratios of poly(ε-caprolactone) (PCL) and LEse block copolymer were dissolved in organic solvent with PL, and then nanofiber mats were fabricated by electro-spinning techniques. Results The higher amount of LEse in the blend of PCL/LEse resulted in the formation of granules while PCL alone showed fine nanofiber structure. Nanofiber mats composed of PCL/LEse polymer blend showed ROS-sensitive drug release, i.e., PL release rate from nanofiber mats was accelerated in the presence of hydrogen peroxide (H2O2) while nanofiber mats of PCL alone have small changes in drug release rate, indicating that PL-incorporated nanofiber membranes have ROS responsiveness. PL itself and PL released from nanofiber mats showed almost similar anticancer activity against various CCA cells. Furthermore, PL released from nanofiber mats properly produced ROS generation and induced apoptosis of CCA cells as well as PL itself. In HuCC-T1 cell-bearing mice, PL-incorporated nanofiber mats showed improvement in anticancer activity. Conclusion PL-incorporated ROS-sensitive nanofiber mats were coated onto GI stent and showed improved anticancer activity with ROS responsiveness. We suggested PL-incorporated ROS-sensitive nanofiber mats as a promising candidate for local treatment of CCA cells.

We evaluated whether the prostate-specific antigen (PSA) mass or free PSA (fPSA) mass (i.e., absolute amount of total circulating PSA or fPSA protein, respectively), versus serum PSA or fPSA concentration, improves the accuracy of predicting the total prostate volume (TPV) in relation to obesity. Among men whose multicore (≥12) transrectal prostate biopsy was negative, 586 who had a PSA of ≤10 ng ml−1 and underwent the fPSA test prior to biopsy were enrolled. The PSA mass or fPSA mass (μ g) was calculated by multiplying the serum level by plasma volume. At each TPV cut-off point (30 ml, 40 ml, and 50 ml), the areas under the receiver operating characteristics curve (AUCs) of each variable were compared in obesity-based subgroups. AUCs of fPSA and fPSA mass for predicting TPV were significantly larger than those for PSA and PSA mass by 8.7%–12.1% at all cut-off points. Subgroup analyses based on obesity showed that, although PSA mass and fPSA mass enhanced accuracy by 4% (P = 0.031) and 1.8% (P = 0.003), respectively, for determining TPVs of ≥30 ml and ≥50 ml in obese and overweight men, they did not improve the accuracy in most other combinations of the degrees of obesity with TPV cut-off points. Thus, compared with serum PSA or fPSA, the absolute amount of PSA or fPSA protein mass improved the accuracy of predicting TPV in obese men very minimally and only for certain TPV cut-off points. Hence, these indicators may not provide clinically meaningful improvement in predicting TPV in obese men.

Understanding the plasticity of genomes has been greatly aided by assays for recombination, repair and mutagenesis. These assays have been developed in microbial systems that provide the advantages of genetic and molecular reporters that can readily be manipulated. Cellular assays comprise genetic, molecular, and cytological reporters. The assays are powerful tools but each comes with its particular advantages and limitations. Here the most commonly used assays are reviewed, discussed, and presented as the guidelines for future studies.

BACKGROUND Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable disease that causes severe mucocutaneous fragility due to mutations in COL7A1 (encoding type VII collagen [C7]). In this phase I/IIa trial, we evaluated the safety and possible clinical efficacy of intravenous infusion of allogeneic human umbilical cord blood–derived mesenchymal stem cells (hUCB-MSCs) in patients with RDEB.METHODS Four adult and two pediatric patients with RDEB were treated with 3 intravenous injections of hUCB-MSCs (1 × 106 to 3 × 106 cells/kg) every 2 weeks and followed up for 8–24 months after treatment. The primary endpoint was safety. Secondary endpoints related to efficacy included clinical parameters, such as disease severity score, wound assessment, itch and pain score, and quality of life. C7 expression levels and inflammatory infiltrates in the skin, as well as serum levels of inflammatory markers and neuropeptides, were also assessed.RESULTS Intravenous hUCB-MSC infusions were well tolerated, without serious adverse events. Improvements in the Birmingham Epidermolysis Bullosa Severity Score, body surface area involvement, blister counts, pain, pruritus, and quality of life were observed with maximal effects at 56–112 days after treatment. hUCB-MSC administration induced M2 macrophage polarization and reduced mast cell infiltration in RDEB skin. Serum levels of substance P were decreased after therapy. Increased C7 expression was observed at the dermoepidermal junction in 1 of 6 patients at day 56.CONCLUSION To the best of our knowledge, this is the first clinical trial of systemic administration of allogeneic hUCB-MSCs in patients with RDEB, demonstrating safety and transient clinical benefits.TRIAL REGISTRATION ClinicalTrials.gov NCT04520022.FUNDING This work was supported by Daewoong Pharmaceutical Co. Ltd. and Kangstem Biotech Co. Ltd.

IntroductionThe optimal salvage treatment strategies for lymph node-positive (LNP) patients after radical surgery have not been clearly defined in prostate cancer with biochemical recurrence or persistence of elevated prostate-specific antigen (PSA). In this study, we compared the clinical outcomes of two different salvage treatments, androgen deprivation therapy (ADT) alone versus ADT with radiotherapy (RT). We also investigated prognostic factors that could support the use of ADT with RT in LNP prostate cancer.Materials and methodsWe retrospectively reviewed 94 LNP prostate cancer patients who underwent radical prostatectomy (RP) followed by salvage treatment between 2004 and 2018. Salvage treatments involved either ADT alone or ADT with RT according to the clinical judgment of the physician. We analyzed clinicopathological and treatment factors related to 2nd biochemical failure (2nd BCF), clinical progression (CP), and progression-free survival (PFS). The cumulative failure after salvage treatment was defined as including both 2nd BCF and CP.ResultsThe median duration of follow-up was 55 months (interquartile range, 35-97 months). Thirty-seven (39.4%) patients were treated with ADT alone, and 57 patients (60.6%) were treated with a combination of ADT with RT. During follow-up period, the incidence of failure after salvage treatment in the ADT alone group and the combined treatment group was 89.2% and 45.6%, respectively (HR, 22.4; 95% CI 5.43-92.1; P < 0.001). The combination of ADT with RT was associated with better 2nd BCF and PFS than ADT alone (P = 0.007 and P = 0.015, respectively). In multivariate analyses, number of positive LN ≥ 2 and PSA nadir ≥ 0.005 ng/ml after RP were associated with poor 2nd BCF, CP, and PFS after salvage treatment. Salvage by combined ADT plus RT showed better 2nd BCF and PFS than ADT alone. Specifically, patients with number of positive LN ≥ 2 or PSA nadir ≥ 0.005 ng/ml after RP showed better 2nd BCF (P = 0.004) or PFS (P = 0.011) when treated with ADT plus RT rather than ADT alone.ConclusionsIn patients with LNP prostate cancer, salvage ADT plus RT improved 2nd BCF and PFS compared to ADT alone. In particular, when the patients had more than two positive lymph nodes or PSA nadir ≥ 0.005 ng/ml after RP, ADT with RT seems to be a more beneficial salvage treatment resulting in better 2nd BCF and PFS.

Background: The prognostic impact and predictors of NOAF in HF patients are not fully elucidated. This study aims to determine whether new-onset atrial fibrillation (NOAF) affects patient outcome and investigate predictors of atrial fibrillation (AF) in acute heart failure (HF) patients using real-world data. Methods: The factors associated with NOAF in 2894 patients with sinus rhythm (SR) enrolled in the Korean Acute Heart Failure (KorAHF) registry were investigated. Survival was analyzed using AF as a time-dependent covariate. Relevant predictors of NOAF were analyzed using multivariate proportional hazards models. Results: Over 27.4 months, 187 patients developed AF. The median overall survival time was over 48 and 9.9 months for the SR and NOAF groups, respectively. Cox regression analysis with NOAF as a time-dependent covariate showed a higher risk of death among patients with NOAF. Multivariate Cox modeling showed that age, worsening HF, valvular heart disease (VHD), loop diuretics, lower heart rate, larger left atrium (LA) diameter, and elevated creatinine levels were independently associated with NOAF. Risk score indicated the number of independent predictors. The incidence of NOAF was 2.9%, 9.4%, and 21.8% in the low-risk, moderate-risk, and high-risk groups, respectively (p < 0.001). Conditional inference tree analysis identified worsening HF, heart rate, age, LA diameter, and VHD as discriminators. Conclusions: NOAF was associated with decreased survival in acute HF patients with SR. Age, worsening HF, VHD, loop diuretics, lower heart rate, larger LA diameter, and elevated creatinine could independently predict NOAF. This may be useful to risk-stratify HF patients at risk for AF.

The yeast Rad1–Rad10 complex has multiple roles in DNA damage repair. Here the authors uncover mutants that uncouple the roles in UV excision repair and non-NER functions.

Abstract Background The prognosis of patients with pathologic stage T3a renal cell carcinoma (RCC) that is up-staged from a small renal tumor remains controversial. We evaluated the prognosis of patients with RCC who were up-staged from clinical stage T1 to pathologic stage T3a. Methods We retrospectively reviewed the data of 3431 patients who were surgically treated for clinical stage T1 RCC. The survival outcomes were compared using Kaplan-Meier and Cox proportional analyses. Results Among the clinical stage T1 patients, 215 (6.3%) were finally up-staged to pathologic stage T3a. Patient age (HR 1.302, 95% CI 1.018–1.046, p 0.5). Conclusions Patients up-staged from clinical stage T1 to pathologic stage T3a RCC showed shorter survival outcomes than those without upstaging. However, partial nephrectomy, compared with radical nephrectomy, showed comparable outcomes in patients who were up-staged.