Diagnostic assessments and treatment results of well-differentiated gastric-type adenocarcinoma of the uterine cervix (Adenoma malignum): A multicenter retrospective analysis of KROG 22-03 study.

OBJECTIVE: Among cervical adenocarcinomas, well-differentiated gastric adenocarcinoma of the uterine cervix (WD-GAS), previously termed adenoma malignum (minimal deviation adenocarcinoma) is not well understood. Because of its rarity and difficulty in diagnosis, there is no standard care for WD-GAS. Thus, we conducted the first multicenter retrospective study on WD-GAS to clarify prognostic factors for long-term survival and recurrence. METHODS: Patients diagnosed with WD-GAS at eight hospitals participated in this multi-center study. Overall survival (OS) and recurrence-free survival (RFS) were calculated with the Kaplan-Meier method. Additionally, OS between the early and advanced FIGO stage groups were compared with the log-rank test. Cox regression analysis was conducted to identify significant factors associated with recurrence-free survival (RFS). RESULTS: A total of 73 patients from eight hospitals in South Korea were included in the analysis. The median follow-up period was 44.8 months, and all patients underwent curative surgical intervention as the primary treatment. Recurrence was observed in 17 patients (23.3%). Ten patients had locoregional recurrence, four patients had distant metastasis, and three patients presented with both locoregional recurrence and distant metastasis. The Cox regression analysis identified several statistically significant factors associated with RFS, including vaginal invasion (VI), parametrial invasion (PMI), resection margin (RM), and nodal and lymphovascular invasion (LVI). When considering these five factors together, patients without any of the factors exhibited recurrence-free survival (RFS) of 97.0% at three years and those with more than one of these factors had a 3-year RFS of 65.4% (P < 0.001). CONCLUSION: WD-GAS showed relatively high locoregional recurrence rate. Positive PMI, VI, RM, nodal involvement, and LVI were associated with a significant increase in recurrence or distant metastasis rates.

Afebrile status at the time of emergency department visit is associated with delayed antibiotic therapy in patients with sepsis (revised).

OBJECTIVES: To determine whether there is a difference in antibiotic administration time and prognosis in afebrile sepsis patients compared to febrile sepsis patients. METHODS: This was retrospective multicenter observational study. Data collected from three referral hospitals. Data were collected from May 2014 through February 2016 under the SEPSIS-2 criteria and from March 2016 to April 2020 under the newly released SEPSIS-3 criteria. Patients were divided into two groups based on body temperature: afebrile (<37.3 °C) and febrile (≥37.3 °C). The relationship between initial body temperature and 28-day mortality were analyzed using multivariable logistic regression. The subgroup analysis was conducted on patients with complete Hour-1 bundle performance records. RESULTS: We included 4293 patients in this study. Initial body temperatures in 28-day survivors were significantly higher than in 28-day non-survivors (37.5 °C ± 1.2 °C versus 37.1 °C ± 1.2 °C, p < 0.01). Multivariable logistic regression analysis was performed in afebrile and febrile sepsis patients. Adjusted odds ratio of afebrile sepsis patients for 28-day mortality was 1.76 (95% Confidence interval 1.46-2.12). As a result of performing the Hour-1 bundle, the number of patients who received antibiotics within 1 h was smaller in the afebrile sepsis patients (323/2076, 15.6%) than in the febrile sepsis patients (395/2156, 18.3%) (p = 0.02). In the subgroup analysis of patients with complete Hour-1 bundle performance records adjusted odds ratio of afebrile sepsis patients for 28-day mortality was 1.68 (95% Confidence interval 1.34-2.11). The febrile sepsis patients received antibiotics faster than the afebrile sepsis patients (175.5 ± 207.9 versus 209.3 ± 277.9, p < 0.01). CONCLUSIONS: Afebrile sepsis patients were associated with higher 28-day mortality compared to their febrile counterparts and were delayed in receiving antibiotics. This underscores the need for improved early detection and treatment strategies for the afebrile sepsis patients.

Circulating mitochondrial N-formyl peptides contribute to secondary nosocomial infection in patients with septic shock.

Secondary infections typically worsen outcomes of patients recovering from septic shock. Neutrophil [polymorphonuclear leukocytes (PMNs)] migration to secondarily inoculated sites may play a key role in inhibiting progression from local bacterial inoculation to secondary infection. Mitochondrial N-formyl peptide (mtFP) occupancy of formyl peptide receptor-1 (FPR1) has been shown to suppress PMN chemotaxis. Therefore, we studied the association between circulating mtFPs and the development of secondary infection in patients with septic shock. We collected clinical data and plasma samples from patients with septic shock admitted to the intensive care unit for longer than 72 h. Impacts of circulating nicotinamide adenine dinucleotide dehydrogenase subunit-6 (ND6) upon clinical outcomes were analyzed. Next, the role of ND6 in PMN chemotaxis was investigated using isolated human PMNs. Studying plasma samples from 97 patients with septic shock, we found that circulating ND6 levels at admission were independently and highly associated with the development of secondary infection (odds ratio = 30.317, 95% CI: 2.904 to 316.407, P = 0.004) and increased 90-d mortality (odds ratio = 1.572, 95% CI: 1.002 to 2.465, P = 0.049). In ex vivo experiments, ND6 pretreatment suppressed FPR1-mediated PMN chemotactic responses to bacterial peptides in the presence of multiple cytokines and chemokines, despite increased nondirectional PMN movements. Circulating mtFPs appear to contribute to the development of secondary infection and increased mortality in patients with septic shock who survive their early hyperinflammatory phase. The increased susceptibility to secondary infection is probably partly mediated by the suppression of FPR1-mediated PMN chemotaxis to secondary infected sites.

Comparison of initial and sequential salvage brain-directed treatment in patients with 1-4 vs. 5-10 brain metastases from breast cancer (KROG 16-12).

PURPOSE: We aimed to compare the initial and salvage brain-directed treatment and overall survival (OS) between patients with 1-4 brain metastases (BMs) and those with 5-10 from breast cancer (BC). We also organized a decision tree to select the initial whole-brain radiotherapy (WBRT) for these patients. METHODS: Between 2008 and 2014, 471 patients were diagnosed with 1-10 BMs. They were divided into two groups based on the number of BM: 1-4 BMs (n = 337) and 5-10 BMs (n = 134). Median follow-up duration was 14.0 months. RESULTS: Stereotactic radiosurgery (SRS)/fractionated stereotactic radiotherapy (FSRT) was the most common treatment modality (n = 120, 36%) in the 1-4 BMs group. In contrast, 80% (n = 107) of patients with 5-10 BMs were treated with WBRT. The median OS of the entire cohort, 1-4 BMs, and 5-10 BMs was 18.0, 20.9, and 13.9 months, respectively. In the multivariate analysis, the number of BM and WBRT were not associated with OS, whereas triple-negative BC and extracranial metastasis decreased OS. Physicians determined the initial WBRT based on four variables in the following order: number and location of BM, primary tumor control, and performance status. Salvage brain-directed treatment (n = 184), mainly SRS/FSRT (n = 109, 59%), prolonged OS by a median of 14.3 months. CONCLUSION: The initial brain-directed treatment differed notably according to the number of BM, which was chosen based on four clinical factors. In patients with ≤ 10 BMs, the number of BM and WBRT did not affect OS. The major salvage brain-directed treatment modality was SRS/FSRT and increased OS.

Battery-Free, Wireless, Cuff-Type, Multimodal Physical Sensor for Continuous Temperature and Strain Monitoring of Nerve.

Peripheral nerve injuries cause various disabilities related to loss of motor and sensory functions. The treatment of these injuries typically requires surgical operations for improving functional recovery of the nerve. However, capabilities for continuous nerve monitoring remain a challenge. Herein, a battery-free, wireless, cuff-type, implantable, multimodal physical sensing platform for continuous in vivo monitoring of temperature and strain from the injured nerve is introduced. The thin, soft temperature, and strain sensors wrapped around the nerve exhibit good sensitivity, excellent stability, high linearity, and minimum hysteresis in relevant ranges. In particular, the strain sensor integrated with circuits for temperature compensation provides reliable, accurate strain monitoring with negligible temperature dependence. The system enables power harvesting and data communication to wireless, multiple implanted devices wrapped around the nerve. Experimental evaluations, verified by numerical simulations, with animal tests, demonstrate the feasibility and stability of the sensor system, which has great potential for continuous in vivo nerve monitoring from an early stage to complete regeneration.

Whole-Genome Sequencing Reveals Mutational Signatures Related to Radiation-Induced Sarcomas and DNA-Damage-Repair Pathways.

Radiation-induced sarcoma (RIS) is a rare but serious late complication arising from radiotherapy. Despite unfavorable clinical outcomes, the genomic footprints of ionizing radiation in RIS development remain largely unknown. Hence, this study aimed to characterize RIS genomes and the genomic alterations in them. We analyzed whole-genome sequencing in 11 RIS genomes matched with normal genomes to identify somatic alterations potentially associated with RIS development. Furthermore, the abundance of mutations, mutation signatures, and structural variants in RIS were compared with those in radiation-naïve spontaneous sarcomas. The mutation abundance in RIS genomes, including one hypermutated genome, was variable. Cancer-related genes might show different types of genomic alterations. For instance, NF1, NF2, NOTCH1, NOTCH2, PIK3CA, RB1, and TP53 showed singleton somatic mutations; MYC, CDKN2A, RB1, and NF1 showed recurrent copy number alterations; and NF2, ARID1B, and RAD51B showed recurrent structural variations. The genomic footprints of nonhomologous end joining are prevalent at indels of RIS genomes compared with those in spontaneous sarcoma genomes, representing the genomic hallmark of RIS genomes. In addition, frequent chromothripsis was identified along with predisposing germline variants in the DNA-damage-repair pathways in RIS genomes. The characterization of RIS genomes on a whole-genome sequencing scale highlighted that the nonhomologous end joining pathway was associated with tumorigenesis, and it might pave the way for the development of advanced diagnostic and therapeutic strategies for RIS.

Total neoadjuvant therapy with short-course radiotherapy Versus long-course neoadjuvant chemoradiotherapy in Locally Advanced Rectal cancer, Korean trial (TV-LARK trial): study protocol of a multicentre randomized controlled trial.

BACKGROUND: For locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT) may enhance tumour response, reduce recurrence, and improve patient compliance compared to upfront surgery. Recent studies have shown that chemoradiotherapy (CRT) followed by consolidation chemotherapy leads to higher rate of pathologic complete response (pCR) than induction chemotherapy followed by CRT. However, an optimal TNT regimen that maximise the pCR rate and minimise toxicity has not been established. Therefore, the aim of this trial was to investigate whether preoperative short-course radiotherapy followed by chemotherapy with four cycles of CAPOX can double the pCR rate compared to a standard schedule of long-course preoperative CRT in patients with LARC. METHODS: This is a multi-centre, prospective, open label, randomised controlled trial. Patients with clinical primary tumour stage 3 and higher or regional node-involved rectal cancer located within 10 cm from the anal verge were randomly assigned equally to short-course radiotherapy (25 Gy in 5 fractions over 1 week) followed by four cycles of CAPOX (intravenous oxaliplatin [130 mg/m2, once a day] on day 1 and capecitabine [1,000 mg/m2, twice a day] from days 1 to 14) (TNT) or CRT (50.4 Gy in 28 fractions over 5 weeks, concurrently with concomitant oral capecitabine 825 mg/m2 twice a day). After preoperative treatment, total mesorectal excision was performed 2-4 weeks in the TNT group and 6-10 weeks in the CRT group, followed by optional additional adjuvant chemotherapy. The primary endpoint is the pCR rate, and secondary endpoints include disease-related treatment failure, quality of life, and cost-effectiveness. Assuming a pCR rate of 28% and 15% in the TNT and CRT groups, respectively, and one-side alpha error rate of 0.025 and power of 80%, 348 patients will be enrolled considering 10% dropout rate. DISCUSSION: The TV-LARK trial will evaluate the superiority of employed TNT regimen against the standard CRT regimen for patients with LARC. We aimed to identify a TNT regimen that will improve the pCR rate and decrease systemic recurrence in these patients. TRIAL REGISTRATION: Cris.nih.go.kr ID: KCT0007169 (April 08, 2022). The posted information will be updated as needed to reflect the protocol amendments and study progress.

Combination Therapy of Niacin and Apocynin Attenuates Lung Injury During Sepsis in Rats.

INTRODUCTION: Oxidative stress contributes to tissue injury through reactive oxygen species-dependent signaling pathways during sepsis. We studied therapeutic benefits of the combination therapy of niacin, which increased reduced glutathione levels, and apocynin, which suppressed reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) activity, in septic rats. MATERIALS AND METHODS: Polymicrobial sepsis was induced through cecal ligation and puncture (CLP) with antibiotics in male Sprague-Dawley rats (n = 189). The rats were randomly divided into sham, CLP, CLP + niacin, CLP + apocynin, and CLP + niacin + apocynin groups. Six hours after CLP, vehicle, niacin (360 mg/kg through the orogastric tube), and/or apocynin (20 mg/kg through intraperitoneal injection) were administered. The occurrence of mortality for 72 h after CLP was observed. Next, a separate set of animals was euthanized at 24 h post-CLP for lung tissue analyses. RESULTS: Combination therapy with niacin and apocynin significantly improved survival in rats with sepsis (75.0% versus 28.8%, P = 0.006) but monotherapy with niacin or apocynin did not. Monotherapy with niacin and apocynin appeared to increase NADPH levels and decrease Nox levels and activity, respectively, but failed to show statistical significances. However, combination therapy significantly decreased Nox levels and activity, increased NADPH and glutathione levels, decreased intranuclear nuclear factor-κB (NF-κB) p65 levels, reduced inflammatory cytokine expression and malondialdehyde levels, and attenuated histological lung injuries. CONCLUSIONS: Combination therapy with niacin and apocynin synergistically attenuated lung injuries and improved survival in rats with sepsis through niacin-induced glutathione redox cycle activation and apocynin-induced Nox suppression.

Interstitial-Induced Ferromagnetism in a Two-Dimensional Wigner Crystal.

The two-dimensional Wigner crystal (WC) occurs in the strongly interacting regime (r_{s}≫1) of the two-dimensional electron gas (2DEG). The magnetism of a pure WC is determined by tunneling processes that induce multispin ring-exchange interactions, resulting in fully polarized ferromagnetism for large enough r_{s}. Recently, Hossain et al. [Proc. Natl. Acad. Sci. U.S.A. 117, 32244 (2020)PNASA60027-842410.1073/pnas.2018248117] reported the occurrence of a fully polarized ferromagnetic insulator at r_{s}≳35 in an AlAs quantum well, but at temperatures orders of magnitude larger than the predicted exchange energies for the pure WC. Here, we analyze the large r_{s} dynamics of an interstitial defect in the WC, and show that it produces local ferromagnetism with much higher energy scales. Three hopping processes are dominant, which favor a large, fully polarized ferromagnetic polaron. Based on the above results, we speculate concerning the phenomenology of the magnetism near the metal-insulator transition of the 2DEG.

New brain metastases after whole-brain radiotherapy of initial brain metastases in breast cancer patients: the significance of molecular subtypes (KROG 16-12).

PURPOSE: To identify the risk factors leading to new brain metastases (BM) following brain-directed treatment for initial BM resulting from breast cancer (BC). METHODS: In this multi-institutional study, 538 BC patients with available follow-up imaging after brain-directed treatment for initial BM were analyzed. Tumor molecular subtypes were classified as follows: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-, n = 136), HER2-positive (HER2+, n = 253), or triple-negative BC (TNBC, n = 149). RESULTS: In 37.4% of patients, new BM emerged at a median of 10.5 months after brain-directed treatment for initial BM. The 1-year actuarial rate of new BM for HR+/HER2-, HER2+, and TNBC were 51.9%, 44.0%, and 69.6%, respectively (p = 0.008). Initial whole-brain radiotherapy (WBRT) reduced new BM rates (22.5% reduction at 1 year, p < 0.001) according to molecular subtype (HR+/HER2-, 42% reduction at 1 year, p < 0.001; HER2+, 18.5%, p = 0.004; TNBC, 16.9%, p = 0.071). Multivariate analysis revealed an increased risk of new BM for the following factors: shorter intervals between primary BC diagnoses and BM (p = 0.031); TNBC (relative to HR+/HER2-) (p = 0.016); presence of extracranial metastases (p = 0.019); number of BM (>4) (p < 0.001); and BM in both tentorial regions (p = 0.045). Anti-HER2 therapy in HER2+ patients (p = 0.013) and initial use of WBRT (p < 0.001) significantly lowered new BM development. CONCLUSIONS: Tumor molecular subtypes were associated with both rates of new BM development and the effectiveness of initial WBRT. Anti-HER2 therapy in HER2+ patients significantly lowered new BM occurrence.

Hypochloraemia is associated with 28-day mortality in patients with septic shock: a retrospective analysis of a multicentre prospective registry.

OBJECTIVES: Hyperchloraemia is associated with poor clinical outcomes in sepsis patients; however, this association is not well studied for hypochloraemia. We investigated the prevalence of chloride imbalance and the association between hypochloraemia and 28-day mortality in ED patients with septic shock. METHODS: A retrospective analysis of data from 11 multicentre EDs in the Republic of Korea prospectively collected from October 2015 to April 2018 was performed. Initial chloride levels were categorised as hypochloraemia, normochloraemia and hyperchloraemia, according to sodium chloride difference adjusted criteria. The primary outcome was 28-day mortality. A multivariate logistic regression model adjusting for age, sex, comorbidities, acid-base state, sepsis-related organ failure assessment (SOFA) score, lactate and albumin level was used to test the association between the three chloride categories and 28-day mortality. RESULTS: Among 2037 enrolled patients, 394 (19.3%), 1582 (77.7%) and 61 (3.0%) patients had hypochloraemia, normochloraemia and hyperchloraemia, respectively. The unadjusted 28-day mortality rate in patients with hypochloraemia was 27.4% (95% CI, 23.1% to 32.1%), which was higher than in patients with normochloraemia (19.7%; 95% CI, 17.8% to 21.8%). Hypochloraemia was associated with an increase in the risk of 28-day mortality (adjusted OR (aOR), 1.36, 95% CI, 1.00 to 1.83) after adjusting for confounders. However, hyperchloraemia was not associated with 28-day mortality (aOR 1.35, 95% CI, 0.82 to 2.24). CONCLUSION: Hypochloraemia was more frequently observed than hyperchloraemia in ED patients with septic shock and it was associated with 28-day mortality.

A phase 2 multicenter study of stereotactic body radiotherapy for hepatocellular carcinoma: Safety and efficacy.

BACKGROUND: Although several prospective studies have reported the efficacy of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC), treatment-related toxicity varies and has not been determined. Therefore, the authors evaluated the safety and efficacy of SBRT for patients with HCC in a hepatitis B virus-endemic area. METHODS: This multicenter phase 2 trial enrolled patients with unresectable HCC. Patients received SBRT with 45 to 60 Gy in 3 fractions. To evaluate gastroduodenal toxicity, esophagogastroduodenoscopy (EGD) was performed before and 2 months after SBRT. The primary endpoint was treatment-related severe toxicity at 1 year after SBRT. The secondary endpoints were the 2-year local control, progression-free survival, and overall survival rates. RESULTS: In total, 74 patients were enrolled between January 2012 and April 2015, and 65 eligible patients were analyzed. One patient experienced radiation-induced liver disease with acute grade ≥3 toxicity 1 month after SBRT. In addition, 1 patient had a grade 3 esophageal ulcer with stenosis 5 months after SBRT. The actuarial rate of treatment-related severe toxicity at 1 year was 3%. The pre-SBRT and post-SBRT EGD findings were not significantly different among the 57 evaluable patients who underwent EGD. The 2-year and 3-year local control rates were 97% and 95%, respectively. The progression-free and overall survival rates were 48% and 84% at 2 years, respectively, and 36% and 76% at 3 years, respectively. CONCLUSIONS: With a median follow-up of 41 months, this prospective multicenter study demonstrated that SBRT for patients with HCC is well tolerated and is an effective treatment modality.

Pulse Oximeter Plethysmograph Variation During Hemorrhage in Beta-Blocker-Treated Swine.

BACKGROUND: Beta-blockers blunt the stress response to hemorrhage. Our aim was to investigate the feasibility of noninvasive pulse oximeter plethysmographic waveform variation (PoPV) for predicting blood volume loss in an esmolol-treated swine hemorrhagic shock model. MATERIALS AND METHODS: Controlled hemorrhage was induced in eight male domestic pigs. In four pigs, a total of 15% and 30% blood volume was drawn step-by-step over 10 min in each step (controlled hemorrhage-only pigs). In the other four pigs, the heart rate (HR) was reduced and maintained by 30% from baseline by esmolol infusion before controlled hemorrhage (esmolol-treated pigs). Diagnostic abilities of HR, pulse pressure variation (PPV), PoPV, and mean arterial pressure for 15% and 30% blood volume loss were determined by the area under the receiver operating characteristic curve (AUC). RESULTS: PoPV was well correlated with PPV in controlled hemorrhage-only pigs (r = 0.717) and esmolol-treated pigs (r = 0.532). In controlled hemorrhage-only pigs, HR (AUC = 0.841 and 0.864), PPV (0.878 and 0.843), and PoPV (0.779 and 0.793) accurately predicted 15% and 30% of blood volume loss. In esmolol-treated pigs, the diagnostic ability of HR was decreased (AUC = 0.766 and 0.733). However, diagnostic abilities of PPV (0.848 and 0.804) and PoPV (0.808 and 0.842) were not deteriorated. CONCLUSIONS: The diagnostic ability of HR for blood volume loss was blunted by esmolol. However, those of PPV and PoPV were not altered. PoPV may be considered to be a useful noninvasive tool to predict blood volume loss in injured patients taking beta-blockers.

Emergency physician-based intensive care unit for critically ill patients visiting emergency department.

BACKGROUND: To provide a prompt and optimal intensive care to critically ill patients visiting our emergency department (ED), we set up and ran a specific type of emergency intensive care unit (EICU) managed by emergency physician (EP) intensivists. We investigated whether this EICU reduced the time interval from ED arrival to ICU transfer (ED-ICU interval) without altering mortality. METHODS: This was a retrospective study conducted in a tertiary referral hospital. We collected data from ED patients who were admitted to the EICU (EICU group) and other ICUs including medical, surgical, and cardiopulmonary ICUs (other ICUs group), from August 2014 to July 2017. We compared these two groups with respect to demographic findings, including the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, ED-ICU interval, ICU mortality, and hospital mortality. RESULTS: Among the 3440 critically ill patients who visited ED, 1815 (52.8%) were admitted to the EICU during the study period. The ED-ICU interval for the EICU group was significantly shorter than that for the other ICUs group by 27.5% (5.0 ±â€¯4.9 vs. 6.9 ±â€¯5.4 h, p < 0.001). In multivariable analysis, the ICU mortality (odds ratio = 1.062, 95% confidence interval 0.862-1.308, p = 0.571) and hospital mortality (odds ratio = 1.093, 95% confidence interval 0.892-1.338, p = 0.391) of the EICU group were not inferior to those of the other ICUs group. CONCLUSIONS: The EICU run by EP intensivists reduced the time interval from ED arrival to ICU transfer without altering hospital mortality.

Anti-Inflammatory Effect of a Peptide Derived from the Synbiotics, Fermented Cudrania tricuspidata with Lactobacillus gasseri, on Inflammatory Bowel Disease.

The objective of this study was to evaluate the effects of peptides derived from synbiotics on improving inflammatory bowel disease (IBD). Five-week-old male C57BL/6 mice were administered with dextran sulfate sodium (DSS) via drinking water for seven days to induce IBD (IBD group). The mice in the IBD group were orally administered with PBS (IBD-PBS-positive control), Lactobacillus gasseri 505 (IBD-Pro), fermented powder of CT extract with L. gasseri 505 (IBD-Syn), ß-casein: LSQSKVLPVPQKAVPYPQRDMP (IBD-Pep 1), or α s2-casein: VYQHQKAMKPWIQPKTKVIPYVRYL (IBD-Pep 2) (both peptides are present in the synbiotics) for four more days while inducing IBD. To confirm IBD induction, the weights of the animals and the disease activity index (DAI) scores were evaluated once every two days. Following treatment of probiotics, synbiotics, or peptides for 11 days, the mice were sacrificed. The length of the small and large intestines was measured. The expression of the proinflammatory cytokines IL-1ß, IL-6, TNF-α, and COX-2 in the large intestine was measured. Large intestine tissue was fixed in 10% formalin and stained with hematoxylin and eosin for histopathological analysis. The body weights decreased and DAI scores increased in the IBD group, but the DAI scores were lower in the IBD-Pep 2 group than those in the IBD group treated with PBS, Pro, Syn, or Pep 1. The lengths of the small and large intestines were shorter in the IBD group than in the group without IBD, and the expression levels of the proinflammatory cytokines were lower (p < 0.05) in the IBD-Pep 2 group than those in the IBD-PBS-positive control group. In addition, histopathological analysis showed that IBD was ameliorated in the Pep 2-treated group. These results indicate that Pep 2 derived from α s2-casein was effective in alleviating IBD-associated inflammation. Thus, we showed that these peptides can alleviate inflammation in IBD.

Prevalence and clinical characteristics of allergic rhinitis in the elderly Korean population.

PURPOSE: The proportion of elderly people aged ≥ 65 years is increasing worldwide. Although the reported prevalence of sinonasal disease can vary according to the diagnostic methods used, differences in allergic rhinitis prevalence in the elderly according to diagnostic method have not been reported. We thus aimed to evaluate allergic rhinitis prevalence in the elderly according to diagnostic criteria obtained from questionnaires, physician diagnoses, and allergy tests. METHODS: We compared the allergic rhinitis prevalence in the elderly aged ≥ 65 years with adults aged 19-64 years, using data from the Korean National Health and Nutrition Examination Survey 2008-2012. Total serum IgE and IgE levels specific to allergens of Dermatophagoides farina, cockroach, and dog dander were examined, and factors affecting specific IgE levels were investigated. RESULTS: Allergic rhinitis prevalence according to the questionnaire responses, physician diagnoses, and allergy test results was 35.02%, 14.89%, and 17.56%, respectively. The prevalence based on all diagnostic methods assessed was significantly lower in the elderly than in the general adult group (p < 0.001). Rhinorrhea incidence was significantly increased in the elderly (p = 0.018). Sensitization to Dermatophagoides farina was significantly decreased in the elderly (p = 0.006) and did not correlate with socioeconomic status and/or general health factors. CONCLUSIONS: The elderly population has a distinct clinical presentation, including a low prevalence of allergic rhinitis, and an increased incidence of rhinorrhea symptoms, compared with the general adult population. The management of allergic rhinitis in elderly patients may therefore require a different therapeutic approach to improve rhinorrhea rather than nasal obstruction.

Delayed endoscopy is associated with increased mortality in upper gastrointestinal hemorrhage.

OBJECTIVES: To determine the association between delayed (>24 h) endoscopy and hospital mortality in patients with upper gastrointestinal hemorrhage (UGIH). METHODS: We retrospectively analyzed all adult patients with UGIH who underwent endoscopy in a single emergency room for 2 years. The primary exposure was defined as >24 h from the ED visit to the first endoscopy. The primary outcome was defined as all cause hospital mortality. Secondary outcomes were intensive care unit admission rate, ED length of stay, and hospital length of stay. RESULTS: Among 1101 patients enrolled, 898 received endoscopy within 24 h (early group) and 203 received endoscopy after 24 h (delayed group). The hospital mortality of early and delayed group was 2.8% and 6.4%, respectively (unadjusted relative risk [RR] 2.30: 95% CI, 1.20-4.42, p = 0.012). This was significant after adjusting covariates including AIMS65 and Glasgow-Blatchford score (adjusted RR 2.23: 95% CI, 1.18-4.20, p = 0.013). Intensive care unit admission rate was not different between two groups. ED and hospital length of stay were significantly longer in delayed group. CONCLUSIONS: Endoscopy performed after 24 h was associated with increased hospital mortality in UGIH. Patients in the delayed group stayed longer in the ED and in the hospital.

Relative tachycardia is associated with poor outcomes in post-cardiac arrest patients regardless of therapeutic hypothermia.

BACKGROUND: To investigate whether the relationship between heart rate and neurological outcome is independent of therapeutic hypothermia (TH) and whether heart rate is related to hemodynamic instability post-cardiac arrest. METHODS: Retrospective review of an out-of-hospital cardiac arrest registry was performed. The primary exposure was heart rate quartiles at 24 h post-cardiac arrest. The primary outcome was a poor neurological outcome, which was defined as having a cerebral performance category (CPC) of 3-5 at 28 days. Secondary outcomes were mean blood pressure and serum lactate at 24 h and Sequential Organ Failure Assessment (SOFA) scores at admission. RESULTS: In total, 155 patients were enrolled. The proportion of patients with a poor CPC was significantly greater in higher heart rate quartiles; similar results were observed in patients who did and did not undergo TH. Serum lactate levels at 24 h were significantly higher in the 3rd and 4th quartile groups than in the 1st quartile group. Additionally, SOFA scores were significantly higher in the 4th quartile group than in the 1st and 3rd quartile groups. CONCLUSIONS: Relative tachycardia is associated with poor neurological outcomes in post-cardiac arrest patients, independent of TH, and with higher serum lactate levels and admission SOFA scores.

Comparison of the clinical characteristics of bilateral and unilateral fungal balls in Korea.

OBJECTIVE: Fungal rhinosinusitis occurs in different forms depending on race and region. While allergic fungal rhinosinusitis is common in Caucasians, fungal ball (FB) is more common in Asians. However, most cases are reported as unilateral, and clinical data on bilateral FB (BFB) are rare. Therefore, the purpose of this study was to analyze and to compare the clinical characteristics of BFB and unilateral FB (UFB) in Koreans. METHODS: We retrospectively analyzed medical records and computed tomography (CT) images of 434 patients diagnosed with FB. The patients were divided into two groups: BFB and UFB. Demographic data, multiple allergen simultaneous test including total or specific immunoglobulin E (IgE) levels, symptoms, CT findings, treatment, and outcomes were analyzed. RESULTS: Among the patients, 26 had BFB and 408 had UFB. Hypertension was noted in 61.5% of the BFB and 39% of the UBF individuals (p = 0.023). While total IgE levels were similar between the two groups, Dermatophagoides pteronyssinus (p = 0.004), Cladosporium (p = 0.017), and Aspergillus-specific IgE positivity (p = 0.025) were significantly higher in the BFB than in the UFB group. Not only symptoms such as postnasal drip (p = 0.013), mucopurulent rhinorrhea (p = 0.009), and foul odor (p = 0.037), but also sphenoid sinus involvement on CT images were more common in the BFB than in the UFB group (p = 0.011). CONCLUSION: Patients with BFB in Korea showed more common hypertension and symptoms of foul odor, mucopurulent rhinorrhea, and postnasal drip with allergy positivity compared to those with UFB. Therefore, understanding clinical characteristics of BFB will allow clinicians to approach BFB more appropriately.