Widespread somatic L1 retrotransposition in normal colorectal epithelium.

Throughout an individual's lifetime, genomic alterations accumulate in somatic cells1-11. However, the mutational landscape induced by retrotransposition of long interspersed nuclear element-1 (L1), a widespread mobile element in the human genome12-14, is poorly understood in normal cells. Here we explored the whole-genome sequences of 899 single-cell clones established from three different cell types collected from 28 individuals. We identified 1,708 somatic L1 retrotransposition events that were enriched in colorectal epithelium and showed a positive relationship with age. Fingerprinting of source elements showed 34 retrotransposition-competent L1s. Multidimensional analysis demonstrated that (1) somatic L1 retrotranspositions occur from early embryogenesis at a substantial rate, (2) epigenetic on/off of a source element is preferentially determined in the early organogenesis stage, (3) retrotransposition-competent L1s with a lower population allele frequency have higher retrotransposition activity and (4) only a small fraction of L1 transcripts in the cytoplasm are finally retrotransposed in somatic cells. Analysis of matched cancers further suggested that somatic L1 retrotransposition rate is substantially increased during colorectal tumourigenesis. In summary, this study illustrates L1 retrotransposition-induced somatic mosaicism in normal cells and provides insights into the genomic and epigenomic regulation of transposable elements over the human lifetime.

DeepNeo: a webserver for predicting immunogenic neoantigens.

Non-self epitopes, whether originated from foreign substances or somatic mutations, trigger immune responses when presented by major histocompatibility complex (MHC) molecules and recognized by T cells. Identification of immunogenically active neoepitopes has significant implications in cancer and virus medicine. However, current methods are mostly limited to predicting physical binding of mutant peptides and MHCs. We previously developed a deep-learning based model, DeepNeo, to identify immunogenic neoepitopes by capturing the structural properties of peptide-MHC pairs with T cell reactivity. Here, we upgraded our DeepNeo model with up-to-date training data. The upgraded model (DeepNeo-v2) was improved in evaluation metrics and showed prediction score distribution that better fits known neoantigen behavior. The immunogenic neoantigen prediction can be conducted at https://deepneo.net.

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.

Factor VII activating protease (FSAP) inhibits the outcome of ischemic stroke in mouse models.

The outcome of ischemic stroke can be improved by further refinements of thrombolysis and reperfusion strategies. Factor VII activating protease (FSAP) is a circulating serine protease that could be important in this context. Its levels are raised in patients as well as mice after stroke and a single nucleotide polymorphism (SNP) in the coding sequence, which results in an inactive enzyme, is linked to an increased risk of stroke. In vitro, FSAP cleaves fibrinogen to promote fibrinolysis, activates protease-activated receptors, and decreases the cellular cytotoxicity of histones. Based on these facts, we hypothesized that FSAP can be used as a treatment for ischemic stroke. A combination of tissue plasminogen activator (tPA), a thrombolytic drug, and recombinant serine protease domain of FSAP (FSAP-SPD) improved regional cerebral perfusion and neurological outcome and reduced infarct size in a mouse model of thromboembolic stroke. FSAP-SPD also improved stroke outcomes and diminished the negative consequences of co-treatment with tPA in the transient middle cerebral artery occlusion model of stroke without altering cerebral perfusion. The inactive MI-isoform of FSAP had no impact in either model. FSAP enhanced the lysis of blood clots in vitro, but in the tail transection model of hemostasis, FSAP-SPD treatment provoked a faster clotting time indicating that it also has pro-coagulant actions. Thus, apart from enhancing thrombolysis, FSAP has multiple effects on stroke progression and represents a promising novel therapeutic strategy in the treatment of ischemic stroke.

Clinical impact of COVID-19 in patients with carbapenem-resistant Acinetobacter baumannii bacteraemia.

The aim of this study was to evaluate the impact of coronavirus disease 2019 (COVID-19) on treatment outcomes in critically ill patients with carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infection (BSI). This single-centre, retrospective cohort study was conducted in a 1,048-bed university-affiliated tertiary hospital in the Republic of Korea from January 2021 to March 2022. The study participants included consecutive hospitalised adult patients (aged ≥18 years) in the intensive care unit with CRAB monomicrobial BSI. During the study period, a total of 70 patients were included in our study, and 24 (34.3%) were diagnosed with COVID-19. The 28-day mortality rate was 64.3%. In the multivariate Cox proportional hazard regression analysis, diagnosis of COVID-19 (hazard ratio (HR), 2.91; 95% confidence interval (CI): 1.45-5.87), neutropenia (HR, 2.76; 95% CI: 1.04-7.29), Pitt bacteraemia score (per point; HR, 1.30; 95% CI: 1.19-1.41), and appropriate definite antibiotic therapy (HR, 0.31; 95% CI: 0.15-0.62) were independent predictors of 28-day mortality in patients with CRAB BSI. In conclusion, our findings suggested that COVID-19 has a negative prognostic impact on patients with CRAB BSI. Further study is needed to investigate the specific mechanisms of how COVID-19 worsens the prognosis of CRAB infection.

Circadian Oscillation of Sulfiredoxin in the Mitochondria.

Hydrogen peroxide (H2O2) released from mitochondria regulates various cell signaling pathways. Given that H2O2-eliminating enzymes such as peroxiredoxin III (PrxIII) are abundant in mitochondria, however, it has remained unknown how such release can occur. Active PrxIII-SH undergoes reversible inactivation via hyperoxidation to PrxIII-SO2, which is then reduced by sulfiredoxin. We now show that the amounts of PrxIII-SO2 and sulfiredoxin undergo antiphasic circadian oscillation in the mitochondria of specific tissues of mice maintained under normal conditions. Cytosolic sulfiredoxin was found to be imported into the mitochondria via a mechanism that requires formation of a disulfide-linked complex with heat shock protein 90, which is promoted by H2O2 released from mitochondria. The imported sulfiredoxin is degraded by Lon in a manner dependent on PrxIII hyperoxidation state. The coordinated import and degradation of sulfiredoxin provide the basis for sulfiredoxin oscillation and consequent PrxIII-SO2 oscillation in mitochondria and likely result in an oscillatory H2O2 release.

Clinical prediction rule for identifying older patients with toxigenic clostridioides difficile at the time of hospital admission.

BACKGROUND: This study aimed to develop and validate a clinical prediction rule to screen older patients at risk of being toxigenic Clostridioides difficile carriers at the time of hospital admission. METHODS: This retrospective case-control study was performed at a university-affiliated hospital. Active surveillance using a real-time polymerase chain reaction (PCR) assay for the toxin genes of C. difficile was conducted among older patients (≥ 65 years) upon admission to the Division of Infectious Diseases of our institution. This rule was drawn from a derivative cohort between October 2019 and April 2021 using a multivariable logistic regression model. Clinical predictability was evaluated in the validation cohort between May 2021 and October 2021. RESULTS: Of 628 PCR screenings for toxigenic C. difficile carriage, 101 (16.1%) yielded positive findings. To establish clinical prediction rules in the derivation cohort, the formula was derived using significant predictors for toxigenic C. difficile carriage at admission, such as septic shock, connective tissue diseases, anemia, recent use of antibiotics, and recent use of proton-pump inhibitors. In the validation cohort, the sensitivity, specificity, and positive and negative predictive values of the prediction rule, based on a cut-off value of ≥ 0.45, were 78.3%, 70.8%, 29.5%, and 95.4%, respectively. CONCLUSION: This clinical prediction rule for identifying toxigenic C. difficile carriage at admission may facilitate the selective screening of high-risk groups. To implement it in a clinical setting, more patients from other medical institutions need to be prospectively examined.

Renovascular hypertension and RNF213 p.R4810K variant in Korean children with Moyamoya disease.

Moyamoya disease (MMD) is the most common underlying disease in Korean pediatric renovascular hypertension (RVH). The ring finger protein 213 (RNF213) p.R4810K variant is reported to be a pathologic variant in East Asian MMD. The purpose of this study was to evaluate hypertension (HTN) prevalence and clinical manifestations as well as RNF213 p.R4810K variant prevalence in Korean pediatric MMD patients. The medical records of pediatric MMD patients from January 2000 to June 2018 were retrospectively reviewed. RVH was confirmed by computer tomography angiography or renal Doppler ultrasonography. The American Academy of Pediatrics 2017 guideline for sex-, age-, and height-related blood pressure standards was used to define HTN. Of 706 patients with MMD, 40 (5.7%) had HTN. Among these patients, 22 had RVH and 12 had HTN with no evidence of renal artery stenosis (non-RVH). Patients with MMD and RVH had an MMD onset at a younger age and lower body mass index compared to those with MMD and non-RVH. Among the patients with MMD and HTN, 4 presented with HTN before developing MMD. Genetic testing for the RNF213 p.R4810K variant was performed in 32 patients with MMD and HTN. When the patient had a homozygous RNF213 p.R4810K variant, the odds ratio of RVH to non-RVH was 8.3. Our study suggests that RVH is more prevalent than non-RVH in pediatric MMD patients. Furthermore, RNF213 p.R4810K may be the cause of RVH in Korean children with MMD.

Refractory ascites induced by mycophenolate in a pediatric kidney transplant patient.

Common side effects of mycophenolate mofetil (MMF) are diarrhea, leukopenia, and infectious complication. The polymorphisms of enzymes affecting MMF clearance could be related to MMF toxicity, and in vitro study revealed that high MMF levels might cause endothelial dysfunction. A 7-year-old Korean male with end-stage renal disease on peritoneal dialysis due to mesangial proliferative glomerulonephritis received a kidney transplantation (KT) from a deceased donor, and immunosuppressive medications including MMF, tacrolimus, and methylprednisolone were started after KT. The patient developed oliguria immediately after surgery, and therapeutic plasmapheresis was initiated with continuous renal replacement therapy for the possibility of graft dysfunction and nephrotic syndrome relapse. Renal function recovered 4 days later, but the patient developed ascites. Diagnostic paracentesis revealed findings that were interpreted as uncomplicated ascites in cirrhosis, not of renal origin. Abdominal ultrasonography showed increased parenchymal echogenicity without cirrhotic change in the liver. Based on a case report and differential diagnosis, we replaced MMF with azathioprine, and 4 weeks later a sudden increment in urine output was detected. Eleven months after KT, the patient is free from ascites. The UGT2B7 802 polymorphism was tested, and wild-type UGT2B7 802 was detected, which is related to low MMF clearance. The low clearance of MMF by UGT2B7 802 wild-type polymorphism might have led to MMF toxicity affecting endothelial dysfunction. This case suggests that refractory ascites could be induced by MMF, and endothelial damage is a possible mechanism.

Clinical and oncologic outcomes of laparoscopic versus open surgery in elderly patients with colorectal cancer: a retrospective multicenter study.

BACKGROUND: Laparoscopic surgery is commonly used in elderly patients over 80 years old. The purpose of this study was to compare the perioperative and oncologic outcomes between laparoscopic surgery and open surgery in elderly patients with colorectal cancer. METHODS: We retrospectively analyzed the medical records of patients aged ≥ 80 years who underwent curative resection of colorectal cancer at six Hallym University-affiliated hospitals. The perioperative outcomes and oncologic outcomes were compared between laparoscopic and open surgery RESULTS: Of 294 elderly patients, 104 (35.3%) underwent open surgery and 190 (64.7%) underwent laparoscopic surgery. The postoperative hospital stay (P = 0.019) and time to soft diet (P = 0.009) were shorter in the laparoscopic group than in the open group. Postoperative complications were less frequent in the laparoscopic group than in the open group (P < 0.001), including wound infection (P = 0.005), ileus (P = 0.005), and pneumonia (P = 0.001). The 3-year overall survival (OS) (P = 0.982) and recurrence-free survival rates (RFS) (P = 0.532) were similar in both groups. In multivariable analyses, positive lymph node status was the only independent factor associated with OS (P = 0.019) and RFS (P = 0.012). Laparoscopic surgery was not associated with OS (P = 0.874) and RFS (P = 0.772). CONCLUSION: Laparoscopic surgery offers several perioperative advantages over open surgery and similar long-term oncological outcomes for elderly patients with colorectal cancer. Therefore, we suggest that laparoscopic surgery can be safely performed for the treatment of elderly patients (≥ 80 years old) with colorectal cancer.

Convolutional neural network model to predict causal risk factors that share complex regulatory features.

Major progress in disease genetics has been made through genome-wide association studies (GWASs). One of the key tasks for post-GWAS analyses is to identify causal noncoding variants with regulatory function. Here, on the basis of >2000 functional features, we developed a convolutional neural network framework for combinatorial, nonlinear modeling of complex patterns shared by risk variants scattered among multiple associated loci. When applied for major psychiatric disorders and autoimmune diseases, neural and immune features, respectively, exhibited high explanatory power while reflecting the pathophysiology of the relevant disease. The predicted causal variants were concentrated in active regulatory regions of relevant cell types and tended to be in physical contact with transcription factors while residing in evolutionarily conserved regions and resulting in expression changes of genes related to the given disease. We demonstrate some examples of novel candidate causal variants and associated genes. Our method is expected to contribute to the identification and functional interpretation of potential causal noncoding variants in post-GWAS analyses.

Clinical outcomes of laparoscopic versus open surgery for repairing colonoscopic perforation: a multicenter study.

PURPOSE: We conducted this study to compare the perioperative outcomes of laparoscopic surgery (LS) vs. open surgery (OS) for repairing colonoscopic perforation, and to evaluate the possible predictors of complications. METHOD: We reviewed the medical records of patients who underwent surgical repair of colonoscopic perforation by LS or OS between January 2005 and June 2019 at six Hallym University-affiliated hospitals. Multivariable analysis was performed to identify the predictors of postoperative complications. RESULTS: Of the total 99 patients, 40 underwent OS and 59 underwent LS. The postoperative hospital stay and the time to resuming a soft diet were shorter in the LS group than in the OS group (P = 0.017 and 0.026, respectively). The complication rate and Clavien-Dindo classification were not significantly different between the two groups. Multivariable analysis revealed that an American Society of Anesthesiologists score (ASA) ≥ 3 and switching from non-operative management to surgical treatment were independently associated with complications (P = 0.025 and 0.010, respectively). CONCLUSION: LS may be a safe alternative to OS for repairing colonoscopic perforation with a shorter postoperative hospital stay and time to resuming a soft diet. Patients with an ASA score ≥ 3 and those with changes to their planned treatment should be monitored carefully to minimize their risk of complications.

Surface-Integrated Electric Field Sensor for the Detection of High-Voltage Power Lines.

When a drone is used for inspection of facilities, there are often cases in which high-voltage power lines interfere, resulting in the drone being caught or falling. To prevent this type of incident, drones must be capable of detecting high-voltage power lines. Typically, a strong electric field is formed around the high-voltage lines. To detect the electric fields around high-voltage lines, this study proposes an electric field sensor that may be integrated within the body of a drone. In a laboratory environment, a voltage of 25 kV was applied to an overhead line, and the induced voltage in the proposed sensor was measured at various electric field intensities. Over an electric field range of 0.5 to 10.1 kV/m, a voltage of 0 to 0.77 V was measured with each proposed sensor. In addition, the electric field and the voltage induced in the sensor were measured in a real-world railway environment with overhead lines. Under these conditions, the proposed sensor has the compensated value of 4.5 when the measured electric field was 4.05 kV/m. Therefore, the proposed sensor may be applied in drones to measure large electric fields and to detect the presence of high-voltage lines in its vicinity.

Clinical outcomes of sigmoid volvulus and risk factors for its recurrence: a multicenter study in Korea.

PURPOSE: Sigmoid volvulus is one of the leading causes of colonic obstruction. The aims of this study were to review the treatment characteristics and clinical outcomes of patients diagnosed with sigmoid volvulus over 10 years at five university-affiliated hospitals in Korea, and to identify possible risk factors for its recurrence. METHODS: Retrospective review was performed for medical records of patients who were diagnosed with sigmoid volvulus and managed surgically or conservatively at the five Hallym University-affiliated hospitals between January 2005 and July 2018. RESULTS: A total of 69 patients were diagnosed, of whom 11 patients underwent emergency surgery and 58 patients were conservatively managed. Non-operative management was successful in 53 of 58 patients (91.4%) at initial admission. Of the non-operative managed patients, six patients required emergency surgery due to unsuccessful decompression or recurrence whereas 23 patients underwent regular surgery for definitive treatment. And overall recurrence rate and mortality rate were 25.8% (15/58) and 1.7% (1/58), respectively. A total of 40 patients underwent surgery; 23 underwent regular surgery and 17 underwent emergency surgery. Restoration of bowel continuity was more frequently performed in the regular surgery group than in the emergency surgery group (87.0% vs 52.9%, P = 0.03). In multivariable analysis, only non-operative management at the initial admission (P = 0.029) was independently associated with recurrence. CONCLUSION: Although non-operative treatment can be initially attempted, surgery is required for preventing recurrence. Regular surgery should be considered to restore continuity of the bowel.

Renal involvement and favorable outcome in a child with mastocytosis.

Mastocytosis is a rare myeloproliferative disease in which mast cells abnormally accumulate in the skin, bone marrow, intestine, liver, spleen, and lymph nodes. Characterized by uncontrolled proliferation of aberrant mast cells, the disease can present either cutaneously or systemically. Mast cells facilitate the immune response and inflammation, and mastocytosis with renal involvement has been rarely reported in adults. Here, we describe a pediatric case of renal involvement in a patient with mastocytosis. A 12-year-old female with mastocytosis was admitted for edema, foamy urine, and gross hematuria. Initial laboratory findings showed azotemia, proteinuria, and hematuria. Renal biopsy findings were compatible with diffuse proliferative glomerulonephritis (DPGN). Immunofluorescence analysis of CD117 (c-Kit) staining resulted positive for rare infiltrating cells. These findings are unusual for primary glomerulonephritis (GN), and secondary GN is typically associated with mastocytosis. According to the literature, steroid treatment can be attempted in cases with renal disease associated with systemic mastocytosis. Therefore, the patient was treated with oral prednisolone, and proteinuria and hematuria disappeared after 4 months of treatment. After 5 months, prednisolone treatment was stopped, and the skin lesion improved. The renal function 22 months after prednisolone treatment was normal. This is a unique report of mastocytosis with DPGN in a child. c-Kit staining can be helpful for diagnosis, and the response to steroid treatment is favorable. Further study about the pathological relevance between mastocytosis and GN is necessary.

Left-ventricular diastolic dysfunction in Korean children with chronic kidney disease: data from the KNOW-Ped CKD study.

BACKGROUND: Cardiovascular disease (CVD) is the most common cause of mortality in pediatric chronic kidney disease (CKD) patients. Left ventricular (LV) hypertrophy (LVH) is associated with LV diastolic dysfunction (LVDD) development and is used as an early marker of CVD in pediatric CKD. This study aimed to assess the prevalence and risk factors of LVDD and the association between LVH and LVDD in Korean pediatric CKD patients. METHODS: Data were collected using the baseline data of the Korean cohort study for outcome in patients with pediatric chronic kidney disease, a nationwide, 10-year, prospective, observational cohort study of pediatric CKD. A total of 244 patients were included in the final analysis. Two-dimensional echocardiography and tissue Doppler images were used to evaluate LVH and LVDD. LVH was defined as an LV mass index (LVMI) ≥38 g/m2.7 and LV-wall thickness z-score > 1.64. LVDD was defined as a mitral peak velocity of early filling to early diastolic mitral annular velocity (E/E') > 14. Univariate and multivariate logistic regression analyses were performed to evaluate risk factors of LVDD. RESULTS: In this study, the male-to-female ratio was 2.2 (168:76) and median age was 11.2 years. The average estimated glomerular filtration rate was 57.4 ml/min/1.73 m2, and no patients received renal replacement therapy. The mean value of LVMI and E/E' was 37.0 g/m2.7 and 7.4, respectively. The prevalence of LVH was 40.1 and 17.4% by LVMI ≥38 g/m2.7 and LV-wall thickness z-score, respectively. The prevalence of LVDD was 4.5%, and patients with LVH showed greater risk of LVDD (odds ratio 7.3, p = 0.012). In the univariate analysis, young age, low hemoglobin level, higher LVMI, and higher LV-wall thickness z-score were associated with LVDD. In the multivariate analysis, young age, low hemoglobin level, and higher LV-wall thickness z-score were independently associated with LVDD. CONCLUSION: This study shows that LVH patients have a greater risk of LVDD and that anemia is the only modifiable risk factor for LVDD in Korean pediatric CKD patients.

Risk of postoperative complications among ulcerative colitis patients treated preoperatively with vedolizumab: a matched case-control study.

BACKGROUND: Although biologic agents have revolutionized the medical management of severe ulcerative colitis (UC), there is considerable controversy regarding adverse effects of vedolizumab on surgical outcomes. We evaluated 30-day postoperative morbidity in UC patients undergoing abdominal colectomy (AC) treated with vedolizumab before surgery. METHODS: From 2007 to 2017, 285 patients were enrolled in prospectively maintained database evaluating the role of clinical, serologic markers with clinical phenotypes in UC. The patients treated with vedolizumab within 12 weeks of AC was queried, then matched 1:3:3 into 3 preoperative treatment groups based on age, gender and surgical treatment of UC; ileal pouch-anal anastomosis (IPAA) with ileostomy vs total colectomy with end stoma: a) vedolizumab (n = 25); b) anti-tumor necrosis factor (anti-TNF) (n = 74); and c) no biologics (n = 54). Thirty-day postoperative complications among patient groups were compared. RESULTS: The 3 patient groups were well-matched in other characteristics including disease duration, disease extent, medication history and preoperative serological data. There were no significant differences in the overall incidence of postoperative complications among patients treated preoperatively with vedolizumab, anti-TNFs, or no biologics (44% vs. 45% vs. 37%; p = 0.67). Although there was no significant difference between patient cohorts in infectious complications (p = 0.20), postoperative ileus (POI) was significantly more common among the vedolizumab group (n = 9; 36%) compared to anti-TNF (n = 12; 16%) or no biologics (n = 5; 9%) (p = 0.01). Multivariable analysis showed that vedolizumab treatment prior to surgery was an independent risk factor for POI (OR: 5.16, 95% CI; 1.71-15.52; p = .004). CONCLUSION: Although preoperative vedolizumab exposure did not influence the rate of overall 30-day postoperative complications, vedolizumab tends to increase incidence of POI.

Prospective randomized clinical trial of uncomplicated right-sided colonic diverticulitis: antibiotics versus no antibiotics.

PURPOSE: Antibiotics are widely used in the treatment of uncomplicated left-sided colonic diverticulitis. In Asian countries, however, right-sided colonic diverticulitis is more common than left-sided colonic diverticulitis. The aim of the present study was to evaluate the need for antibiotics in the treatment of uncomplicated right-sided colonic diverticulitis in an Asian population. METHODS: Patients were randomized to two management strategies: antibiotics and no antibiotics. At 4-6 weeks after discharge, the patients in both groups underwent computed tomography or were contacted by phone to confirm the effectiveness of the treatment. The primary end point was the treatment failure rate of the initial treatment, and secondary end points were the length of hospital stay and total admission costs. RESULTS: Patients were randomized to treatment with (61 patients) or without (64 patients) antibiotics. The rates of treatment failure in the antibiotics and no antibiotics groups were 1.7% and 4.6%, respectively, with no significant difference (P = 0.619). There was also no significant difference in the length of hospital stay between the groups (P = 0.983). Total admission costs were lower in the no antibiotics group than in the antibiotics group (US$1004.70 vs US$1112.40, respectively, P = 0.037). CONCLUSION: Conservative management of uncomplicated right-sided colonic diverticulitis without antibiotics shows similar treatment failure rates and length of hospital stay, and is associated with lower hospital costs, compared with standard antibiotic treatment. Therefore, conservative management can be considered as a safe treatment option. TRIAL REGISTRATION: ClinicalTrial.gov No. NCT02314013.

Factors contributing to excessive daytime sleepiness in Korean adults with epilepsy: A sleep questionnaire-based study.

OBJECTIVES: We determined factors contributing to excessive daytime sleepiness (EDS) in Korean adults with epilepsy (AWE). METHODS: A total of 147 AWE who had been treated for >1 year were included. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS). Subjective sleep disturbances were assessed with the Sleep Apnea of Sleep Disorder Questionnaire (SA-SDQ) and questionnaires about insomnia and restless legs syndrome (RLS). The Hospital Anxiety and Depression Scale (HADS) was also used. An ESS score >10 was considered indicative of EDS. Multivariate logistic regression analyses using the backward elimination method were performed for variables with a p < 0.10 on univariate analysis. RESULTS: The mean ESS score was 6.8 (standard deviation [SD]: 4.4). Among the 147 subjects, 36 (24.5%) had EDS. Multivariate logistic regression analysis showed that being employed (odds ratio [OR]: 4.469, p < 0.01), the presence of at least one sleep disturbance (OR: 3.626, p < 0.01), and antiepileptic drug (AED) polytherapy (OR: 2.663, p < 0.05) were independently associated with EDS in the overall group of AWE. In contrast, being employed (p < 0.05) and higher Hospital Anxiety and Depression Scale-Anxiety subscale (HADS-A) scores (p < 0.05) in a model for men with epilepsy, as well as having at least one sleep disturbance (p < 0.05) in a model for women with epilepsy, were identified as independent factors for EDS. CONCLUSIONS: Excessive daytime sleepiness in AWE may have a multifactorial origin. Being employed, subjective sleep disturbances, and AED polytherapy are independent predictors of EDS. There may be sex differences in factors associated with EDS.