Global translational reprogramming is a fundamental layer of immune regulation in plants.

In the absence of specialized immune cells, the need for plants to reprogram transcription to transition from growth-related activities to defence is well understood. However, little is known about translational changes that occur during immune induction. Using ribosome footprinting, here we perform global translatome profiling on Arabidopsis exposed to the microbe-associated molecular pattern elf18. We find that during this pattern-triggered immunity, translation is tightly regulated and poorly correlated with transcription. Identification of genes with altered translational efficiency leads to the discovery of novel regulators of this immune response. Further investigation of these genes shows that messenger RNA sequence features are major determinants of the observed translational efficiency changes. In the 5' leader sequences of transcripts with increased translational efficiency, we find a highly enriched messenger RNA consensus sequence, R-motif, consisting of mostly purines. We show that R-motif regulates translation in response to pattern-triggered immunity induction through interaction with poly(A)-binding proteins. Therefore, this study provides not only strong evidence, but also a molecular mechanism, for global translational reprogramming during pattern-triggered immunity in plants.

Overexpression of arogenate dehydratase reveals an upstream point of metabolic control in phenylalanine biosynthesis.

Out of the three aromatic amino acids, the highest flux in plants is directed towards phenylalanine, which is utilized to synthesize proteins and thousands of phenolic metabolites contributing to plant fitness. Phenylalanine is produced predominantly in plastids via the shikimate pathway and subsequent arogenate pathway, both of which are subject to complex transcriptional and post-transcriptional regulation. Previously, it was shown that allosteric feedback inhibition of arogenate dehydratase (ADT), which catalyzes the final step of the arogenate pathway, restricts flux through phenylalanine biosynthesis. Here, we show that in petunia (Petunia hybrida) flowers, which typically produce high phenylalanine levels, ADT regulation is relaxed, but not eliminated. Moderate expression of a feedback-insensitive ADT increased flux towards phenylalanine, while high overexpression paradoxically reduced phenylalanine formation. This reduction could be partially, but not fully, recovered by bypassing other known metabolic flux control points in the aromatic amino acid network. Using comparative transcriptomics, reverse genetics, and metabolic flux analysis, we discovered that transcriptional regulation of the d-ribulose-5-phosphate 3-epimerase gene in the pentose phosphate pathway controls flux into the shikimate pathway. Taken together, our findings reveal that regulation within and upstream of the shikimate pathway shares control over phenylalanine biosynthesis in the plant cell.

The rice heavy-metal transporter OsNRAMP1 regulates disease resistance by modulating ROS homoeostasis.

Crop diseases threaten food security and sustainable agriculture. Consumption of crops containing nonessential toxic metals leads to health risks for humans. Therefore, cultivation of disease-resistant and toxic metal-safe crops is a double-gain strategy that can contribute to food security. Here, we show that rice heavy-metal transporter OsNRAMP1 plays an important role in plant immunity by modulating metal ion and reactive oxygen species (ROS) homoeostasis. OsNRAMP1 expression was induced after pathogenic bacteria and fungi infections. The osnramp1 mutants had an increased content of H2 O2 and activity of superoxide dismutase, but decreased activity of catalase, showing enhanced broad-spectrum resistance against bacterial and fungal pathogens. RNA-seq analysis identified a number of differentially expressed genes that were involved in metal ion and ROS homoeostasis. Altered expression of metal ion-dependent ROS-scavenging enzymes genes and lower accumulation of cations such as Mn together induced compromised metal ion-dependent enzyme-catalysing activity and modulated ROS homoeostasis, which together contributed towards disease resistance in osnramp1 mutants. Furthermore, the osnramp1 mutants contained lower levels of toxic heavy metals Cd and Pb and micronutrients Ni and Mn in leaves and grains. Taken together, a proof of concept was achieved that broad-spectrum disease-resistant and toxic heavy-metal-safe rice was engineered by removal of the OsNRAMP1 gene.

Bone-density testing interval and transition to osteoporosis in differentiated thyroid carcinoma patients on TSH suppression therapy.

OBJECTIVE: Thyrotropin (TSH) suppression therapy is a standard treatment after surgery for differentiated thyroid carcinoma (DTC). It may be associated with osteoporosis in postmenopausal women. However, there are no guidelines for bone mineral density (BMD) testing intervals to screen for osteoporosis in these patients. Therefore, we evaluated the timing of repeated BMD testing in DTC patients with TSH suppression according to baseline T-scores. DESIGN, PATIENTS, AND MEASUREMENT: We retrospectively evaluated 658 DTC patients who underwent BMD testing more than twice between January 2007 and January 2020. A 1:3 propensity score matching was conducted to compare the timing of repeated BMD tests between the DTC and non-DTC groups. We stratified the participants into four groups based on their baseline T-scores: normal (-1.00 or higher), mild osteopenia (-1.01 to -1.49), moderate osteopenia (-1.50 to -1.99), and severe osteopenia (-2.00 to -2.49). Additionally, the 10% of patients in each group that transitioned to osteoporosis were analysed. RESULTS: The estimated BMD testing interval for 10% of patients who developed osteoporosis was 85 months for patients with initially mild osteopenia, 65 months for those with moderate osteopenia, and 15 months for those with severe osteopenia in the DTC group. In the non-DTC group, the testing intervals for mild, moderate, and severe osteopenia were 98, 57, and 13 months, respectively. On multivariate analysis, baseline T-score (mild osteopenia: hazard ratio [HR] 5.91, p = .105; moderate osteopenia: HR, 25.27, p = .02; and severe osteopenia: HR, 134.82, p < .001) and duration of TSH suppression (tertile 2: HR, 2.25, p = .005; Tertile 3: 1.78, p = .033) were independent risk factors for osteoporosis in the DTC group. CONCLUSION: This study provides guidance for the timing of repeated BMD tests in women over 50 years of age with TSH suppression. The rescreening interval for BMD testing can be modified based on the baseline T-score. The appropriate BMD testing intervals in female DTC patients were similar to those in non-DTC females.

Separation of native and C106-oxidized DJ-1 proteins by using column chromatography.

Mutations in PARK7, the gene encoding the DJ-1 protein, are associated with early onset of Parkinson's disease. The C106 residue of DJ-1 is highly susceptible to oxidation, and its oxidation status is essential for various in vivo neuroprotective roles. Since C106 is readily oxidized to sulfinic acid that is not reduced by dithiothreitol, no method to separate native DJ-1 protein from the oxidized one creates challenges in the in vitro study of the biological relevance of C106-oxidation state. Here, we report an efficient column chromatography method to purify native, C106-sulfinic, and mixed (combination of the priors) forms of DJ-1. This method will be useful for systematic in vitro studies of DJ-1 functions by providing specific native and C106-sulfinic DJ-1 proteins.

Eradication of Helicobacter pylori infection decreases risk for dyslipidemia: A cohort study.

BACKGROUND: Previous studies have suggested a relationship between Helicobacter pylori infection and dyslipidemia; however, large-scale longitudinal studies have not elucidated this association. This study assessed the longitudinal effects of H. pylori infection and eradication on lipid profiles in a large cohort. METHODS: This cohort study included 2,626 adults without dyslipidemia at baseline, who participated in a repeated, regular health-screening examination, which included upper gastrointestinal endoscopy, between January 2009 and December 2018. The primary outcome was incident dyslipidemia at follow-up. RESULTS: During the 10,324 person-years of follow-up, participants with persistent H. pylori infection had a higher incidence rate (130.5 per 1,000 person-years) of dyslipidemia than those whose infections had been successfully controlled (98.1 per 1,000 person-years). In a multivariable model adjusted for age, sex, waist circumference, smoking status, alcohol intake, and education level, the H. pylori eradication group was associated with a lower risk of dyslipidemia than the persistent group (HR, 0.85; 95% CI, 0.77-0.95; p = 0.004). The association persisted after further adjustment for baseline levels of low-density and high-density lipoprotein cholesterol (HR, 0.87; 95% CI, 0.79-0.97; p = 0.014). CONCLUSIONS: H. pylori infection may play a pathophysiologic role in the development of dyslipidemia, whereas H. pylori eradication might decrease the risk of dyslipidemia.

A Scoring Model with Simple Clinical Parameters to Predict Successful Discontinuation of Continuous Renal Replacement Therapy.

BACKGROUND: Continuous renal replacement therapy (CRRT) is the standard treatment for severe acute kidney injury in critically ill patients. However, a practical consensus for discontinuing CRRT is lacking. We aimed to develop a prediction model with simple clinical parameters for successful discontinuation of CRRT. METHODS: Adult patients who received CRRT at Samsung Medical Center from 2007 to 2017 were included. Patients with preexisting ESRD and patients who progressed to ESRD within 1 year or died within 7 days after CRRT were excluded. Successful discontinuation of CRRT was defined as no requirement for renal replacement therapy for 7 days after discontinuing CRRT. Patients were assigned to either a success group or failure group according to whether discontinuation of CRRT was successful or not. RESULTS: A total of 1,158 patients were included in the final analyses. The success group showed greater urine output on the day before CRRT discontinuation (D-1) and the discontinuation day (D0). Multivariable analysis identified that urine output ≥300 mL on D-1, and mean arterial pressure 50∼78 mm Hg, serum potassium <4.1 mmol/L, and BUN <35 mg/dL (12.5 mmol/L) on D0 were predictive factors for successful discontinuation of CRRT. A scoring system using the 4 variables above (area under the receiver operating curve: 0.731) was developed. CONCLUSIONS: Scoring system composed of urine output ≥300 mL/day on D-1, and adequate blood pressure, serum potassium <4.1 mmol/L, and BUN <35 mg/dL (12.5 mmol/L) on D0 was developed to predict successful discontinuation of CRRT.

Clinical Factors Associated with Renal Outcome After Heart Transplantation.

Cardiorenal syndrome (CRS) frequently occurs in end-stage heart failure patients waiting for heart transplantation (HT). Decision-making regarding simultaneous heart and kidney transplantation is an unresolved issue in these patients. We investigated clinical factors associated with renal outcome after HT. A total of 180 patients who received HT from 1996 to 2015 were included. Factors associated with early post-HT chronic kidney disease (CKD, estimated glomerular filtration rate [eGFR] < 60 mL/minute/1.73 m2 within 1 year post-HT), post-HT end-stage kidney disease (ESKD), and significant renal function improvement (%ΔeGFR > 15%) at 1 year post-HT were analyzed. Early post-HT CKD and post-HT ESKD developed in 61 (33.9%) and 8 (4.4%) of 180 patients, respectively. Old age was only independently associated with early post-HT CKD and preexisting CKD tended to be associated with early post-HT CKD. Old age and preexisting CKD were independently associated with post-HT ESKD. Low pre-HT eGFR and preoperative renal replacement therapy were not associated with early post-HT CKD or post-HT ESKD. Young age, low pre-HT eGFR, and high %ΔeGFR 1 month post-HT were independently associated with significant renal function improvement. Preoperative renal function, including preoperative RRT, was not associated with post-HT mortality. In conclusion, preexisting CKD may impact renal outcomes after HT, but preoperative severe renal dysfunction, even that severe enough to require RRT, may not be a contraindication for HT alone. Our data suggest the necessity of early HT in end-stage heart failure patients with CRS and the importance of careful management during the early postoperative period.

The combination of area under the curve and percentage change in estimated glomerular filtration rate predicts long-term outcome of kidney transplants.

The development of surrogate markers for long-term outcomes of kidney transplant (KT) is a focus of attention. We examined the possibility of using a combination of the area under the curve of estimated glomerular filtration rate (eGFR) for 2 years (AUCeGFR2yrs ) and percent change in eGFR between 1 and 2 years after KT (% changeeGFR1/2yr ) as a surrogate marker. We compared the predictive power of death-censored graft failure with various combinations. The combination of >2% vs ≤2% for % changeeGFR1/2yr and >1300 vs ≤1300 mL/min/month for AUCeGFR2yr had the highest Harrell C-index (0.647; 95% confidence interval [95% CI], 0.604-0.690). The death-censored graft survival rate of the group with ≤2% changeeGFR1/2yr and ≤1300 mL/min/month AUCeGFR2yr was significantly lower than those of other groups. The AUC/% change eGFR had comparable predictive power to the previously identified marker ≥30% decline in eGFR between years 1 and 3 after KT (≤-30% changeeGFR1/3yr ) (Harrell's C-index = 0.645 [95% CI 0.628-0.662] for ≤-30% changeeGFR1/3yr ). The proposed combination might be useful as a surrogate marker in KT trials because it requires a shorter surveillance period than the established marker while having comparable predictive power.

Prognostic factors associated with long-term mortality in 1445 patients with nontuberculous mycobacterial pulmonary disease: a 15-year follow-up study.

Limited data are available regarding the prognostic factors for patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). We investigated the prognostic factors associated with long-term mortality in NTM-PD patients after adjusting for individual confounders, including aetiological organism and radiological form.A total of 1445 patients with treatment-naïve NTM-PD who were newly diagnosed between July 1997 and December 2013 were included. The aetiological organisms were as follows: Mycobacterium avium (n=655), M. intracellulare (n=487), M. abscessus (n=129) and M. massiliense (n=174). The factors associated with mortality in NTM-PD patients were analysed using a multivariable Cox model after adjusting for demographic, radiological and aetiological data.The overall 5-, 10- and 15-year cumulative mortality rates for the NTM-PD patients were 12.4%, 24.0% and 36.4%, respectively. On multivariable analysis, the following factors were significantly associated with mortality in NTM-PD patients: old age, male sex, low body mass index, chronic pulmonary aspergillosis, pulmonary or extrapulmonary malignancy, chronic heart or liver disease and erythrocyte sedimentation rate. The aetiological organism was also significantly associated with mortality: M. intracellulare had an adjusted hazard ratio (aHR) of 1.40, 95% CI 1.03-1.91; M. abscessus had an aHR of 2.19, 95% CI 1.36-3.51; and M. massiliense had an aHR of 0.99, 95% CI 0.61-1.64, compared to M. avium Mortality was also significantly associated with the radiological form of NTM-PD for the cavitary nodular bronchiectatic form (aHR 1.70, 95% CI 1.12-2.59) and the fibrocavitary form (aHR 2.12, 95% CI 1.57-3.08), compared to the non-cavitary nodular bronchiectatic form.Long-term mortality in patients with NTM-PD was significantly associated with the aetiological NTM organism, cavitary disease and certain demographic characteristics.

Dual kidney transplantation offers a safe and effective way to use kidneys from deceased donors older than 70 years.

PURPOSE: Dual kidney transplantation (DKT) offers a way to extend the use of kidneys from expanded criteria donors (ECDs). Here, we compared the outcomes of DKT with those of single kidney transplantation from standard criteria donors (SCDs) and ECDs. METHODS: In 2014, we began performing DKT using both kidneys from deceased donors greater than 70 years of age with one of two risk factors: serum creatinine (sCr) level over 3.0 mg/dl or eGFR under 30 ml/min. By 2017, we had performed 15 DKTs. We compared the outcomes of the 15 DKT recipients with those of 124 patients who received a kidney from an SCD and 80 patients who received a kidney from an ECD. RESULTS: Compared with ECDs and SCDs, DKT donors were older, had a higher diabetes burden, and a higher sCr level (p < 0.01, < 0.01, and 0.03, respectively). DKT recipients were also older and had a higher diabetes burden than recipients of kidneys from ECDs and SCDs (p < 0.01, both). DKT recipients had a lower nadir sCr and shorter duration to nadir sCr than single ECD KT recipients (p < 0.01and 0.04, respectively). CONCLUSIONS: The survival rates of DKT grafts were compatible with those of single KT grafts. Therefore, DKT may be considered a suitable an option to expand the donor pool.

Young Age and Risk of Lymph Node Metastasis in Differentiated Type Early Gastric Cancer.

BACKGROUND: Young patients with gastric cancer reportedly have a worse prognosis than older patients due to delayed diagnosis and more aggressive tumor behavior. However, it is unclear whether this applies to early gastric cancer (EGC), for which endoscopic resection is indicated. We investigated the association between age and lymph node metastasis (LNM). METHODS: We identified 4055 patients diagnosed with EGC of differentiated histology who underwent surgery. The association between age and LNM was examined using logistic regression for each T stage separately with adjustments for multiple covariates. We compared LNM rates for each of the Japanese Endoscopic Resection Guidelines criteria in younger (< 40 years) and older patients (40 years). RESULTS: The median number of lymph nodes examined was the same for T1a and T1b stages (n = 34). The median number of lymph nodes examined was not significantly different within T1a stage (P = 0.093), but within T1b stage, the number of lymph nodes examined was significantly different (P = 0.019). The highest number was between 50 and 59 years (median = 37), and the lowest number was in the 20 to 49 years and older than 70 age brackets (median = 34). LNM rate and age were not significantly associated within each stage (P values 0.269, 0.783 for T1a and T1b, respectively). Among patients fulfilling endoscopic resection criteria, the LNM rate in younger patients was lower than in older patients. CONCLUSIONS: In differentiated-type EGC, young age at diagnosis was not associated with LNM rate. Therefore, endoscopic resection criteria for early gastric cancer can be applied to younger patients.

Which approach is preferred in left hepatocellular carcinoma? Laparoscopic versus open hepatectomy using propensity score matching.

BACKGROUND: Laparoscopic liver resection has been reported as a safe and effective approach for the management of hepatocellular carcinoma (HCC). However, its perioperative and oncological outcomes have not been evaluated in left hepatectomy patients. The aim of the present study is to compare the outcomes of left hepatectomy through laparoscopic and open approaches in left HCC. METHODS: From December 2012 to October 2016, laparoscopic left hepatectomy (LLH) was performed in 40 patients and open left hepatectomy (OLH) was performed in 80 patients. All clinical data were analyzed retrospectively. Propensity score matching of patients in a 1:1 ratio was conducted based on tumor size and presence of microvascular invasion. RESULTS: Tumor size and presence of microvascular invasion were higher in the OLH group than the LLH group (P < 0.05). However, the operative time was longer in the LLH group than in the OLH group (266 min vs. 239 min; P = 0.005). The median postoperative hospital stay was significantly shorter in the LLH group than in the OLH group before and after matching (9 days vs. 13 days; P < 0.001). The incidence of complications in the LLH and OLH groups was 10.0 and 7.5%, respectively. The disease-free survival (DFS) and overall survival (OS) in the LLH group were not different from those in the OLH group after propensity score matching. CONCLUSIONS: A laparoscopic approach is feasible and safe for left HCC. The oncologic outcome of LLH is comparable to that of OLH.

Ten-year observational follow-up of a randomized trial comparing cyclosporine and tacrolimus therapy combined with steroid withdrawal in living-donor renal transplantation.

Although various strategies for steroid withdrawal after transplantation have been attempted, there are few reports of the long-term results of steroid withdrawal regimens in kidney transplantation. Earlier, we reported on a 5-year prospective, randomized, single-center trial comparing the safety and efficacy of cyclosporine (CsA) plus mycophenolate mofetil (MMF) with that of tacrolimus (TAC) plus MMF, when steroids were withdrawn 6 months after kidney transplantation in low-risk patients. We now report the 10-year observational data on the study population. We collected data from the database of the Organ Transplantation Center, Samsung Medical Center for 5 years after completion of the original study (TAC group n = 62; CsA group n = 55). The 10-year patient survival, death-censored graft survival, and acute rejection-free survival did not differ between groups (98% vs 96%; P = 0.49, 78% vs 85%; P = 0.75 and 84% vs 76%; P = 0.14 in the TAC group vs CsA group, respectively). In low-risk patients, there was no difference in long-term patient and graft survival between TAC- and CsA-based late steroid withdrawal regimens that included MMF treatment. More long-term randomized clinical trials are needed to clarify the benefits of late steroid withdrawal in kidney transplantation.

Indication for endoscopic treatment based on the risk of lymph node metastasis in patients with Siewert type II/III early gastric cancer.

BACKGROUND: Because of the poor prognosis of proximal gastric cancers, there is debate as to whether the conventional indications for endoscopic resection can be used. METHODS: Among subjects who underwent surgery for esophagogastric junction or gastric cardia cancer, 256 patients with T1 type II/III of the Siewert classification were included in this study. The association of lymph node metastasis (LNM) with each variable was analyzed using logistic regression models. A receiver operating characteristic curve was used to determine the discriminatory ability of the model. Propensity score-matched non-cardia cancer patients were selected to compare LNM and long-term survival rates. RESULTS: Of the 256 patients with T1 Siewert II/III gastric cancer, 21 (8.2%) had LNM. Because there was no LNM in T1a cancers, risk factors were analyzed only in patients with T1b. Tumor size (OR 1.42, 95% CI 1.10-1.82, P = 0.007) and lymphovascular invasion (LVI) (OR 5.13, 95% CI 1.88-14.06, P = 0.002) were determined to be predictors of LNM (sensitivity = 66.7% and specificity = 81.6%). Among patients without LVI, the groups with negligible risk for LNM were mucosa-confined cancer, or SM1 cancer with a tumor size ≤3 cm. No LNM was observed in patients satisfying the absolute or extended criteria for endoscopic resection of early gastric cancers. LNM and long-term survival rates of patients with Siewert II/III did not differ significantly compared with matched non-cardia cancer patients. CONCLUSIONS: Tumor size and LVI were associated with LNM in patients with early Siewert type II/III gastric cancer, and the expanded indication for endoscopic resection may be used.

Spatial and temporal regulation of biosynthesis of the plant immune signal salicylic acid.

The plant hormone salicylic acid (SA) is essential for local defense and systemic acquired resistance (SAR). When plants, such as Arabidopsis, are challenged by different pathogens, an increase in SA biosynthesis generally occurs through transcriptional induction of the key synthetic enzyme isochorismate synthase 1 (ICS1). However, the regulatory mechanism for this induction is poorly understood. Using a yeast one-hybrid screen, we identified two transcription factors (TFs), NTM1-like 9 (NTL9) and CCA1 hiking expedition (CHE), as activators of ICS1 during specific immune responses. NTL9 is essential for inducing ICS1 and two other SA synthesis-related genes, phytoalexin-deficient 4 (PAD4) and enhanced disease susceptibility 1 (EDS1), in guard cells that form stomata. Stomata can quickly close upon challenge to block pathogen entry. This stomatal immunity requires ICS1 and the SA signaling pathway. In the ntl9 mutant, this response is defective and can be rescued by exogenous application of SA, indicating that NTL9-mediated SA synthesis is essential for stomatal immunity. CHE, the second identified TF, is a central circadian clock oscillator and is required not only for the daily oscillation in SA levels but also for the pathogen-induced SA synthesis in systemic tissues during SAR. CHE may also regulate ICS1 through the known transcription activators calmodulin binding protein 60g (CBP60g) and systemic acquired resistance deficient 1 (SARD1) because induction of these TF genes is compromised in the che-2 mutant. Our study shows that SA biosynthesis is regulated by multiple TFs in a spatial and temporal manner and therefore fills a gap in the signal transduction pathway between pathogen recognition and SA production.

Comparison of Long-Term Outcomes After Non-curative Endoscopic Resection in Older Patients with Early Gastric Cancer.

BACKGROUND: Limited data exist that describe the long-term outcomes from additional surgery following non-curative endoscopic resection (ER) of early gastric cancer (EGC) in older people. This study aimed to determine the appropriate treatment strategy for these patients. METHODS: We analyzed data from 2895 patients who underwent ER for EGC, of whom 451 (15.6%) had non-curative resections followed by curative surgery or surveillance only. Of these patients, 138 were older (aged ≥70 years). We compared the long-term outcomes of the different treatment strategies in the older patients with non-curative resections for EGC, and the outcomes of each treatment strategy, with those in younger patients. RESULTS: The older patients underwent curative resections, non-curative resections with surgery, or non-curative resections with surveillance, and the 5-year disease-specific survival (DSS) rates were 100, 100, and 73%, respectively. There was a trend toward significance for DSS in favor of the non-curative resections with surgery group compared with the non-curative resections with surveillance-only group (p = 0.069). Among those who did not undergo additional surgery, the older patients had worse DSS than the younger patients, and patients who underwent additional surgery had better DSS, irrespective of their ages. Multivariable analysis adjusted for other-cause mortality generated similar results. Overall survival and recurrence-free survival did not differ according to treatment strategy, and perioperative morbidity and mortality did not differ significantly according to age. CONCLUSIONS: In older patients with non-curatively resected EGC, additional surgery demonstrated a trend toward better DSS, and perioperative complications did not increase significantly.

Diagnostic accuracy of diffusion restriction in intraductal papillary mucinous neoplasm of the pancreas in comparison with "high-risk stigmata" of the 2012 international consensus guidelines for prediction of the malignancy and invasiveness.

Background It is debated whether diagnostic performance of diffusion-weighted imaging (DWI), which is widely used for detection and characterization of various malignant tumors, is comparable with high-risk stigmata of 2012 international consensus guidelines (ICG) for diagnosis of intraductal papillary mucinous neoplasms (IPMNs). Purpose To evaluate the diagnostic accuracy of diffusion restriction in IPMNs for prediction of malignancy and invasiveness in comparison with high-risk stigmata of 2012 ICG. Material and Methods This retrospective study was institutional review board approved and informed consent was waived. A total of 132 patients with surgically proven IPMNs (49 malignant, 83 benign) who underwent gadoxetic acid-enhanced magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), and DWI with a b-value of 0, 100, and 800 s/mm2 using a 3.0 T MR system were included. Two radiologists independently evaluated imaging parameters of high-risk stigmata and worrisome features of 2012 ICG and diffusion restriction in IPMNs. Univariate and multivariate logistic regression analyses and McNemar's test were used for statistical analysis. Results The presence of diffusion restriction in IPMNs was the only independent imaging parameter for prediction of malignancy (odds ratio [OR], 11.98; 95% confidence interval [CI], 3.60-39.87; P < 0.001) and invasiveness (OR, 17.92; 95% CI, 3.91-82.03; P < 0.001) on multivariate analysis. The diagnostic accuracy and specificity of diffusion restriction were significantly improved compared to high-risk stigmata of 2012 ICG to prediction of malignant ( P = 0.006 and P < 0.001, respectively) or invasive IPMNs ( P = 0.009 and P = 0.015, respectively). Conclusion The diffusion restriction in IPMNs could be considered as another high-risk stigma of malignancy and predictor for invasiveness.

Reference Values and Utility of Serum Total Immunoglobulin E for Predicting Atopy and Allergic Diseases in Korean Schoolchildren.

The present study aimed to investigate the distribution of total serum immunoglobulin E (IgE) levels in Korean schoolchildren and to evaluate its utility in the prediction of atopy and allergic diseases. A nationwide, cross-sectional survey was conducted in first grade students from randomly selected elementary and middle schools. Total IgE levels were measured by ImmunoCAP. Skin prick tests were performed for 18 common inhalant allergens to determine the presence of atopy. Children aged 12-13 years and parents of children aged 6-7 years were asked to complete questionnaire assessing allergic diseases. The cut-off levels of total IgE were determined by analyzing receiver operating characteristic curves. The median total IgE level was 86.7 kU/L (range: 1.5-4,523.1) in 3,753 children aged 6-7 years and 94.7 kU/L (range: 1.5-3,000.0) in 3,930 children aged 12-13 years. Total IgE concentrations were higher in children with atopy or allergic diseases than in those without (all P < 0.001). At the cut-off value of 127.7 kU/L, sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were 67.1%, 75.4%, 65.4%, and 76.7%, respectively, in elementary schoolchildren. At the cut-off value of 63.0 kU/L, sensitivity, specificity, PPV, and NPV were 81.9%, 66.6%, 75.0%, and 75.1%, respectively, in middle schoolchildren. PPV and NPV were ≥ 70% when cut-offs of 258.8 kU/L and 38.4 kU/L were used for the diagnosis of atopy in 6-7 year-olds and 12-13 year-olds, respectively. This nationwide population-based study provided the first normal reference ranges of total IgE in Korean schoolchildren.

Distinct spatiotemporal patterns of cortical thinning in Alzheimer's disease-type cognitive impairment and subcortical vascular cognitive impairment.

Previous studies on Alzheimer's disease-type cognitive impairment (ADCI) and subcortical vascular cognitive impairment (SVCI) has rarely explored spatiotemporal heterogeneity. This study aims to identify distinct spatiotemporal cortical atrophy patterns in ADCI and SVCI. 1,338 participants (713 ADCI, 208 SVCI, and 417 cognitively unimpaired elders) underwent brain magnetic resonance imaging (MRI), amyloid positron emission tomography, and neuropsychological tests. Using MRI, this study measures cortical thickness in five brain regions (medial temporal, inferior temporal, posterior medial parietal, lateral parietal, and frontal areas) and utilizes the Subtype and Stage Inference (SuStaIn) model to predict the most probable subtype and stage for each participant. SuStaIn identifies two distinct cortical thinning patterns in ADCI (medial temporal: 65.8%, diffuse: 34.2%) and SVCI (frontotemporal: 47.1%, parietal: 52.9%) patients. The medial temporal subtype of ADCI shows a faster decline in attention, visuospatial, visual memory, and frontal/executive domains than the diffuse subtype (p-value < 0.01). However, there are no significant differences in longitudinal cognitive outcomes between the two subtypes of SVCI. Our study provides valuable insights into the distinct spatiotemporal patterns of cortical thinning in patients with ADCI and SVCI, suggesting the potential for individualized therapeutic and preventive strategies to improve clinical outcomes.