Vimentin citrullination probed by a novel monoclonal antibody serves as a specific indicator for reactive astrocytes in neurodegeneration.

AIMS: Vimentin citrullination, the calcium (Ca2+ )-dependent peptidylarginine deiminase (PAD)-mediated conversion of an arginine residue of vimentin to a citrulline residue, has emerged as a pathophysiological outcome of autoimmune diseases and neurodegeneration. However, the roles, functions, and expression of citrullinated vimentin have not yet been elucidated because available antibodies are limited. METHODS: We developed mouse monoclonal IgG1 and IgM specific for vimentin citrullinated at position R440 or R450 and applied Western blotting, immunohistochemistry, and immunofluorescent staining to investigate the pathogenesis of prion diseases in animal models, in patients with prion diseases, and in vitro. RESULTS: Vimentin was found to be highly citrullinated at R440 and R450, and these citrullinated forms were mainly expressed in reactive astrocytes in the brain tissues of scrapie-infected mice. Full-length and cleaved forms of citrullinated vimentin were found in the cerebral cortices of sporadic Creutzfeldt-Jakob disease (sCJD) patients. The distribution of citrullinated vimentin was mainly confirmed in vimentin-, GFAP-, and YKL-40-positive reactive astrocytes. Biochemically, citrullination promoted resistance to the caspase-3- and caspase-9-mediated fragmentation of vimentin. Additionally, citrullination led to increased cytoplasmic and integral membrane/organelle vimentin enrichment, which indicated changes in the intrinsic solubility and distribution of vimentin. CONCLUSIONS: Our observations suggest that citrullinated vimentin acts as a specific indicator for the reactive state of astrocytes under abnormal neurological conditions. In addition, these novel antibodies will be helpful for studying the role of citrullinated vimentin in the pathogenesis of human disorders.

Sleep problems in Korean children with Down syndrome and parental quality of life.

BACKGROUND: Sleep problems are common among children with Down syndrome (DS), and they can have a serious impact on children with DS as well as their parents and other family members. Specific aims of this study were to evaluate parent-reported sleep problems in children with DS and to examine the relationship between the sleep behaviour of children with DS and their parents' quality of life (QOL). METHOD: A cross-sectional survey was conducted in September and October of 2017. Parents of children with DS were recruited from an online self-support community for parents of children with DS in South Korea. The mean age of the parents and children with DS was 40.40 years (SD = 5.09) and 7.89 years (SD = 3.03), respectively. Children's sleep problems and parents' QOL were assessed using the Children's Sleep Habits Questionnaire and the abbreviated version of the World Health Organization Quality of Life scale, respectively. RESULTS: Results revealed that 83% of the parents reported that their child with DS experienced sleep problems. Children with DS had significantly more bedtime resistance, night waking, parasomnias and sleep-disordered breathing than did typically developing children. In addition, their Children's Sleep Habits Questionnaire scores were higher than those of typically developing children. Moreover, being older, being male and having more severe developmental delays were significant risk factors for sleep problems among children with DS. Furthermore, sleep problems in children with DS negatively affected parents' QOL. CONCLUSIONS: Sleep problems negatively affect children with DS as well as their parents; therefore, health care providers should be aware of these issues and help parents manage sleep problems proactively.

Body mass index and 20 specific cancers: re-analyses of dose-response meta-analyses of observational studies.

Background: Objectives were to provide an overview and understand the strength of evidence and extent of potential biases and validity of claimed associations between body mass index (BMI) and risk of developing cancer. Methods: We carried out an umbrella review and comprehensively re-analyzed the data of dose-response meta-analyses on associations between BMI and risk of 20 specific cancers (bladder, brain, breast, colonic, rectal, endometrial, gallbladder, gastric, leukemia, liver, lung, melanoma, multiple myeloma, non-Hodgkins lymphoma, esophagus, ovarian, pancreatic, prostate, renal, thyroid) by adding big data or missed individual studies. Convincing evidence for an association was defined as a strong statistical significance in fixed-effects and random-effects meta-analyses at P < 0.001, 95% prediction interval (PI) excluded null, there was no large between-study heterogeneity and no small study effects. Suggestive evidence was defined as meeting the significance threshold for the random summary effects of P < 0.05, but 95% PI included the null. Weak evidence was defined as meeting the significance threshold for the random summary effects at a P < 0.05, but 95% PI included the null and there was large between-study heterogeneity or there were small study effects. Results: Convincing evidence for an association with BMI was detectable for six cancers (leukemia, multiple myeloma, pancreatic, endometrial, rectal, and renal cell carcinoma). Suggestive evidence was detectable for malignant melanoma, non-Hodgkins lymphoma, and esophageal adenocarcinoma. Weak evidence was detectable for brain and central nervous system tumors, breast, colon, gall bladder, lung, liver, ovarian, and thyroid cancer. No evidence was detectable for bladder, gastric, and prostate cancer. Conclusions: The association of increased BMI and cancer is heterogeneous across cancer types. Leukemia, multiple myeloma, pancreatic, endometrial, rectal, and renal cell carcinoma are convincingly associated with an increased BMI by dose-response meta-analyses.

Good for the lung but bad for the liver? Garlic-induced hepatotoxicity following liver transplantation.

WHAT IS KNOWN AND OBJECTIVE: Limited data exist surrounding the metabolism and safety of garlic supplements. CASE DESCRIPTION: A patient with a history of hepatopulmonary syndrome (HPS) and orthotopic liver transplantation was admitted to our surgery transplant service with severe hypoxaemia. The patient was started on high-dose Garlicin Cardio® (Allium sativum) for HPS and soon after had elevated liver function tests. Garlicin Cardio® was discontinued and liver enzymes normalized. A liver biopsy revealed mild periportal cholestatic reaction suggesting potential drug-induced aetiology. WHAT IS NEW AND CONCLUSION: This is the first description of liver injury secondary to garlic supplementation. Therefore, this garlic supplement should be listed as a potential cause of acute drug-induced liver injury.

Long-term outcome of transanal irrigation for children with spina bifida.

STUDY DESIGN: Experimental, prospective study. OBJECTIVES: We evaluated the long-term clinical efficacy of transanal irrigation (TAI) and its effect on the quality of life of spina bifida children and their caregivers. SETTING: Republic of Korea. METHOD: Forty-four spina bifida pediatric patients with constipation, fecal incontinence or both, underwent a TAI program at our spina bifida clinic between December 2010 and October 2013. The children and their caregivers were evaluated using a self-administered questionnaire before TAI and at 3 months and 3 years after initiation of the program. RESULTS: Successful treatment outcome was achieved in 38 (86.4%) children after a mean follow-up duration of 33 months (range, 30-36). The mean number of fecal incontinence episodes per week, the number of diaper changes and the total time for bowel care per day before the program decreased at the latest follow-up examination from 7.3 to 0.4 (P<0.001), 1.6 to 0.2 (P<0.001) and 29.2 to 19.4 min (P=0.038), respectively. These results remained constant from short-term follow-up at 3 months to 3 years. Caregivers and children could go out more often (P=0.002), and the emotional impact of bowel care on caregivers decreased (P<0.001). The reported mean overall satisfaction with TAI was 8/10. The common adverse effect during TAI was abdominal discomfort (60.5%). CONCLUSION: We observed a sustained significant improvement in defecation symptoms and quality of life for 3 years in spina bifida children who underwent continuous TAI.

Development and validation of Chemotherapy-induced Alopecia Distress Scale (CADS) for breast cancer patients.

BACKGROUND: A psychometric scale for assessing the distress that breast cancer patients experience due to the chemotherapy-induced alopecia was developed and validated. PATIENTS AND METHODS: Twenty-five items for chemotherapy-induced alopecia distress were developed based on a qualitative study, and a cross-sectional survey was conducted with 305 Korean women with breast cancer. To extract factor structure and evaluate construct validity, exploratory and confirmatory factor analysis (CFA) was carried out. Concurrent and discriminant validity were tested by correlations with the psychosocial factors. In addition, external validity analysis was conducted using data from another prospective study of 428 breast cancer patients. RESULTS: Exploratory factor analysis and CFA yielded 17 items in four domains and the model fit was good (CFI=0.925). Coefficient alphas ranged from 0.77 to 0.95 for subdomains and 0.95 for total, and it was similar with the validation dataset confirming its external validity. The total Chemotherapy-Induced Alopecia Distress Scale (CADS) was moderately correlated with the body image (r=-0.47, P<0.001), more weakly correlated with the patients' overall quality of life (QOL, r=-0.28, P<0.001), but did not correlate with self-esteem (r=-0.07, P=0.23). CONCLUSIONS: Our study confirmed that the CADS is a reliable and valid tool for measuring distress of chemotherapy-induced alopecia.

Effect of palonosetron on the QTc interval in patients undergoing sevoflurane anaesthesia.

BACKGROUND: Palonosetron is a recently introduced 5-HT3 receptor antagonist for postoperative nausea and vomiting. Detailed standardized evaluation of corrected QT (QTc) interval change by palonosetron under sevoflurane anaesthesia is lacking. We evaluated QTc intervals in patients who are undergoing surgery with sevoflurane anaesthesia and receive palonosetron. METHODS: Our study included 100 patients who were undergoing elective surgery under sevoflurane anaesthesia. The patients were randomly assigned to two groups: those who received an i.v. injection of palonosetron 0.075 mg immediately before induction of anaesthesia (pre-surgery group, n=50) and those who received it after surgery in the recovery room (post-surgery group, n=50). QTc intervals were measured before operation, intraoperatively (baseline, immediately after tracheal intubation, and at 2, 10, 15, 30, 60, and 90 min after administration of palonosetron or placebo), and after operation (before and at 3, and 10 min after administration of palonosetron or placebo). QTc intervals were calculated using Fridericia's, Bazett's, or Hodges formulas. RESULTS: The perioperative QTc intervals were significantly increased from the baseline values, but were not affected by the pre- or post-surgical timing of palonosetron administration. CONCLUSIONS: There was no significant difference in the QTc intervals during the perioperative period, whether 0.075 mg of palonosetron is administered before or after sevoflurane anaesthesia. Palonosetron may be safe in terms of QTc intervals during sevoflurane anaesthesia. Clinical trial registration ClinicalTrials.gov: NCT01650961.

INCB018424 induces apoptotic cell death through the suppression of pJAK1 in human colon cancer cells.

Janus kinase (JAK) is one of the main upstream activators of signal transducers and activators of transcription (STAT) that are constitutively activated in various malignancies and are associated with cell growth, survival, and carcinogenesis. Here, we investigated the role of JAKs in colorectal cancer in order to develop effective therapeutic targets for INCB018424, which is the first JAK1/2 inhibitor to be approved by FDA. After examining the basal expression levels of phospho-JAK1 and phospho-JAK2, we measured the effects of INCB018424 on the phosphorylation of JAK1/2 using western blot analysis. Cell viability was determined using the trypan blue exclusion assay. The cell death mechanism was identified by the activation of caspase 3 using western blot and annexin V staining. The basal levels of phospho-JAK1 and phospho-JAK2 were cancer cell type dependent. Colorectal cancer cell lines that phosphorylate both JAK1 and JAK2 include DLD-1 and RKO. INCB018424 inactivates both JAK1 and JAK2 in DLD-1 cells but inactivates only JAK1 in RKO cells. Cell death was proportional to the inactivation of JAK1 but not JAK2. INCB018424 causes caspase-dependent cell death, which is prevented by treatment with z-VAD. The inhibition of JAK1 phosphorylation seemed sufficient to allow INCB018424-mediated apoptosis. JAK1 is a key molecule that is involved in colon cancer cell survival and the inhibition of JAK1 by INCB01424 results in caspase-dependent apoptosis in colorectal cancer cells. The use of selective JAK1 inhibitors could be an attractive therapy against colorectal cancer, but further clinical investigations are needed to test this possibility.

Phase III trial of concurrent thoracic radiotherapy with either first- or third-cycle chemotherapy for limited-disease small-cell lung cancer.

BACKGROUND: We compared late thoracic radiotherapy (TRT) with early TRT in the treatment of limited-disease small-cell lung cancer (LD-SCLC). PATIENTS AND METHODS: Patients with LD-SCLC received four cycles of etoposide plus cisplatin every 21 days. Patients were randomly assigned to receive either TRT administered concurrently with the first cycle (early TRT) or the third cycle (late TRT) of chemotherapy. The primary end point was complete response rate. RESULTS: Two hundred twenty-two patients were randomly assigned.Late TRT was not inferior to early TRT in terms of the complete response rate (early v late; 36.0% v 38.0%). Other efficacy measures including overall survival [median, 24.1 v 26.8 months;hazard ratio (HR) 0.93; 95% CI = 0.67­1.29] and progression free survival (median, 12.4 v 11.2 months; HR 1.09; 95%CI = 0.80­1.48) were not different between two arms. No statistical difference was noted in the pattern of treatment failures.However, neutropenic fever occurred more commonly in the early TRT arm than the late TRT arm (21.6% v 10.2%; P = 0.02) [corrected]. CONCLUSION: In LD-SCLC treatment, TRT starting in the third cycle of chemotherapy seemed to be noninferior to early TRT, and had a more favorable profile with regard to neutropenic fever.

Stage IE/IIE extranodal NK/T-cell lymphoma arising in the nasal cavity: analysis of CT findings and their prognostic value.

AIM: To investigate the computed tomography (CT) findings in patients with stage IE/IIE extranodal natural killer/T-cell lymphoma (ENKTL) arising in the nasal cavity and to evaluate whether imaging findings revealed by CT have prognostic value. MATERIALS AND METHODS: The CT findings of 62 patients diagnosed with IE/IIE ENKTL arising in the nasal cavity were retrospectively reviewed. Imaging findings were investigated, and evaluated imaging findings were analysed for the prognostic value of overall survival (OS) and disease-free survival (DFS). RESULTS: Of the 62 patients, 21 (34%) presented with a superficial infiltrative, 38 (61%) with a mass forming, and three (5%) with a combined pattern. Of all imaging findings, local invasiveness (n = 26, 42%), including bony destruction, erosion, or soft-tissue involvement, was the only independent prognostic factor for OS [p = 0.008; hazard ratio (HR): 3.85; 95% confidence intervals (CI): 1.42-10.44] and DFS (p = 0.001; HR: 4.25; 95% CI: 1.72-10.47). In a subgroup analysis of 36 cases with no local invasiveness, a superficial infiltrative pattern in one nasal cavity was a positive prognostic factor for OS (p = 0.028) and DFS (p = 0.008). CONCLUSION: Imaging findings at CT provided clinically useful predictions for treatment outcomes. Local invasiveness revealed by CT findings was a strong prognostic factor for poor OS and DFS. In addition, in patients with no local invasiveness, a superficial infiltrative pattern in one nasal cavity predicted favourable OS and DFS.

The effects of transanal irrigation as a stepwise bowel management program on the quality of life of children with spina bifida and their caregivers.

STUDY DESIGN: Experimental, prospective study. OBJECTIVES: Fecal incontinence and constipation affect the quality of life (QOL) of children with spina bifida and their caregivers. We evaluated the clinical efficacy of a stepwise bowel management program on QOL for children with spina bifida and their caregivers. SETTING: Republic of Korea. METHODS: Between December 2010 and April 2011, 53 children with constipation, fecal incontinence or both underwent a stepwise bowel management program at our spina bifida clinic. The children and their caregivers were evaluated before and after this program using a self-administered questionnaire. RESULTS: Among the children, 11.3% received only oral laxatives and controlled well, 88.7% received transanal irrigation. After this program, the mean number of episodes of fecal incontinence per week, number of diaper changes and total time for bowel care decreased from 6.9 to 0.5 (P=0.004), from 1.6 to 0.2 (P=0.001) and from 27 to 15.9 min (P=0.003), respectively. Caregivers and children were able to leave their houses more often (P=0.006), and caregivers' bothersomeness, anxiety and depression due to bowel care decreased (P<0.001). Factors related to family relationships (P=0.265) and financial impact (P=0.071) improved, but not significantly. CONCLUSIONS: We observed significant improvement in defecation symptoms and QOL scores of spina bifida patients who underwent this program. We recommend that this simple therapeutic method be considered as a safe and valid choice for the treatment of chronic constipation and fecal incontinence.

Calsenilin: a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment.

Most early-onset familial Alzheimer disease (AD) cases are caused by mutations in the highly related genes presenilin 1 (PS1) and presenilin 2 (PS2). Presenilin mutations produce increases in beta-amyloid (Abeta) formation and apoptosis in many experimental systems. A cDNA (ALG-3) encoding the last 103 amino acids of PS2 has been identified as a potent inhibitor of apoptosis. Using this PS2 domain in the yeast two-hybrid system, we have identified a neuronal protein that binds calcium and presenilin, which we call calsenilin. Calsenilin interacts with both PS1 and PS2 in cultured cells, and can regulate the levels of a proteolytic product of PS2. Thus, calsenilin may mediate the effects of wild-type and mutant presenilins on apoptosis and on Abeta formation. Further characterization of calsenilin may lead to an understanding of the normal role of the presenilins and of the role of the presenilins in Alzheimer disease.

Genetic polymorphism in exon 2 of cathepsin D is not associated with vascular dementia.

BACKGROUND: Cathepsin D, the most abundant lysosomal and endosomal aspartyl protease, shows beta and gamma secretase activity in vitro by cleaving the amyloid precursor protein (APP) into amyloid beta protein (Aß). Polymorphism at position 224, C224T, on exon 2 of cathepsin D gene (CTSD) has been associated with an increased risk for Alzheimer's disease (AD) by some investigators, but there have been contrary findings by others. However, an association between CTSD polymorphism and vascular dementia (VaD) has not been reported thus far. OBJECTIVE: To investigate whether a polymorphism at CTSD C224T is associated with VaD in the Korean population. METHODS: We compared the genotype and allele frequencies at this polymorphism site in clinically assessed 162 VaD patients with those in 197 healthy Koreans. RESULTS AND CONCLUSION: The major genotype frequency at CTSD C224T in normal controls was higher in the Asian population than in various European populations. Our study does not show a significant difference in genotype (P=0.3071) and allele (P=0.2291) frequencies of CTSD C224T between VaD and normal controls. This was the first genetic association study of CTSD in a VaD population.

Ketorolac or fentanyl continuous infusion for post-operative analgesia in children undergoing ureteroneocystostomy.

BACKGROUND: children undergoing ureteroneocystostomy suffer from post-operative pain due to the surgical incision and bladder spasm. A single-shot caudal block is a common technique for paediatric analgesia, but a disadvantage is the limitation of a short duration in spite of the additives co-administered. A few clinical trials have shown that ketorolac provides an effective post-operative analgesia and reduces the bladder spasms after ureteral implantation in children. We compared the efficacy of a continuous infusion of ketorolac and fentanyl in post-operative analgesia and bladder spasm in children who underwent ureteroneocystostomy. METHODS: fifty-two children were allocated to the ketorolac group (Group K, n=26) and fentanyl group (Group F, n=26). After general anaesthesia, a caudal block was performed with 1.5 ml/kg of 0.15% ropivacaine. At the beginning of surgery, an infusion was started after the bolus injection of ketorolac 0.5 mg/kg or fentanyl 1 microg/kg. An infusion device was programmed to deliver ketorolac 83.3 microg/kg/h or fentanyl 0.17 microg/kg/h for 48 h. RESULTS: two of Group F and three of Group K were excluded from the study. Post-operative pain scores were similar between the two groups. One of Group K (4%) and seven of Group F (30.4%) experienced bladder spasms. The rescue analgesic requirements were significantly less in Group K. CONCLUSIONS: a Continuous infusion of ketorolac provided effective analgesia after operation in children who underwent ureteroneocystostomy as well as a low dosage of fentanyl. Ketorolac was more effective in reducing the frequency of bladder spasms and rescue analgesic requirements.

Optimal dose of propofol for intubation after sevoflurane inhalation without neuromuscular blocking agent in children.

BACKGROUND: This study was designed to determine the optimal dose of propofol for excellent intubating conditions in children without neuromuscular blockade at various alveolar concentrations of sevoflurane. METHODS: Sixty-three children, aged 0.5-5 years, were randomized to three groups of end-tidal sevoflurane concentration (ETsevo) 3%, 3.5%, and 4%. Inhalation anesthesia was started with sevoflurane 7% in 100% oxygen. When the patients became unconscious, inspired concentration was adjusted to obtain the target ETsevo for each group. When ETsevo reached the target concentration, a predetermined dose of propofol was given and tracheal intubation was performed. The proper dose of propofol was determined using the 'up-and-down' method. RESULTS: The median dose (95% confidence intervals) of propofol for excellent tracheal intubating conditions in 50% of children were 1.25 mg/kg (0.84-1.75) at ETsevo of 3%, 0.76 mg/kg (0.35-1.21) at 3.5%, and 0.47 mg/kg (0.26-1.09) at 4%. The frequency of adverse effects was not different between groups during induction and recovery. CONCLUSION: Propofol 1.5-2 mg/kg provides excellent intubating conditions at 3-4% ETsevo in children without using any neuromuscular blocking agent.

Omega-3 fatty acids supplementation on major cardiovascular outcomes: an umbrella review of meta-analyses of observational studies and randomized controlled trials.

OBJECTIVE: Omega-3 fatty acids are commonly used as a lipid-lowering agent or dietary supplement for the purpose of prevention of cardiovascular diseases. However, even large-scale clinical trials have not shown significant results demonstrating clear clinical benefits in cardiovascular diseases. Thus, this umbrella review aims to summarize and evaluate the evidence of clinical effects of omega-3 fatty acids supplementation on cardiovascular outcomes through comprehensive analyses of previous randomized controlled trials (RCTs) or observational cohort studies. MATERIALS AND METHODS: We conducted relevant publication search in PubMed, Embase, and Cochrane Database of Systematic Reviews. We retrieved and analyzed 3,298 articles published until August 28th, 2019. RESULTS: We identified 29 relevant articles and analyzed 83 meta-analyses of RCTs or cohort studies therefrom. As a result, we identified 12 cardiovascular outcomes that are related to omega-3 fatty acids supplementation. Among them, total mortality from major cardiovascular causes (RR 0.92, 95% CI 0.86 to 0.98) had significant inverse associations, and moreover, statistical significances were maintained even in subgroup analysis of large-scale RCTs including more than 1,000 patients (RR 0.94, 95% CI 0.88 to 0.99). CONCLUSIONS: Our umbrella review study shows that omega-3 fatty acids supplementation have a clinical benefit in reducing mortality from cardiovascular causes. However, many studies still have shown conflicting results, and therefore, further studies will be needed to verify the clinical benefit of omega-3 supplementation.

Recombinant human epidermal growth factor treatment of radiation-induced severe oral mucositis in patients with head and neck malignancies.

Mucositis of the oral cavity and pharynx is a major dose-limiting factor in the application of radiotherapy (RT) to patients with head and neck cancer. Therefore, we evaluated the wound healing effect of human recombinant epidermal growth factor (rhEGF) in head and neck cancer and lymphoma patients with irradiation (with or without combined chemotherapy-induced oral mucositis). Patients at Asan Medical Center who had undergone definitive RT of the head and neck region with or without combined chemotherapy and who had developed severe oral mucositis (higher than the Radiation Therapy Oncology Group grade 3) were treated with topical rhEGF twice daily for 7 days. The evaluation of response with regard to oral mucositis was performed 1 week later. Of the 11 treated patients, three had nasopharyngeal carcinoma, three had carcinoma of the oropharynx, two had carcinoma of the oral cavity, one had carcinoma of the hypopharynx and two had lymphoma of the head and neck. Six patients received RT only, and five patients received concurrent chemoradiotherapy. All patients showed improvements in their oral mucositis after topical treatment with rhEGF in that the Radiation Therapy Oncology Group grade was significantly decreased (P = 0.0000). This finding suggests that rhEGF is effective and safe for the treatment of radiation-induced mucositis. Further studies are needed to determine the optimal dosage and fractionation schedule.

Outcomes after combined laparoscopic gastrectomy and laparoscopic cholecystectomy in gastric cancer patients.

BACKGROUND/AIMS: The purpose of this study was to determine the effect of performing laparoscopic cholecystectomy on patients undergoing laparoscopic-assisted gastrectomy for gastric cancer. METHODS: This single center study involved a retrospective review of a database of 400 patients who underwent consecutive laparoscopic-assisted gastrectomy for early gastric cancer from June 2003 to July 2007. Outcomes in 26 patients who underwent both laparoscopic-assisted gastrectomy and laparoscopic cholecystectomy were compared with outcomes from 364 patients who underwent laparoscopic-assisted gastrectomy without laparoscopic cholecystectomy. RESULTS: There were no postoperative 30-day mortalities in the combined cholecystectomy group. The mean surgery duration, time to first flatus and postoperative hospital stay for the laparoscopic gastric resection without combined operation were 181.7 min, 2.7 days and 9.7 days, respectively, and 196.7 min, 2.6 days and 8.8 days, respectively, for the combined cholecystectomy group. None of the postoperative complications was related to combined cholecystectomy. CONCLUSION: Performing a combined cholecystectomy prolonged the mean surgery duration by approximately 15 min, but had no effect on surgical outcomes. It appears that performing a cholecystectomy at the same time as laparoscopic gastric resection is safe and feasible in patients with both early gastric cancer and gallbladder disease.

Tooth Loss Predicts Myocardial Infarction, Heart Failure, Stroke, and Death.

We investigated whether oral health, represented by missing teeth, was associated with an increased risk of cardiovascular disease, including myocardial infarction (MI), heart failure (HF), stroke, and all-cause mortality. Subjects who underwent routine dental examinations and health checkups provided by the Korean National Health Insurance from 2007 to 2008 ( n = 4,440,970) were followed up for incident MI, HF, stroke, and death until 2016. During follow-up of 7.56 y, 68,063 (1.5%) subjects died, and 31,868 (0.7%) were admitted for MI, 22,637 (0.5%) for HF, and 30,941 (0.7%) for stroke. Cardiovascular events and mortality increased in proportion to tooth loss. Tooth loss was an independent risk factor for cardiovascular events after multivariable analysis adjusted for cardiovascular risk, behavioral, and income factors. Each missing tooth was associated with an approximately 1% increase in MI (HR, 1.010; 95% CI, 1.007 to 1.014), 1.5% increase in HF (HR, 1.016; 95% CI, 1.013 to 1.019) and stroke (HR, 1.015; 95% CI, 1.012 to 1.018), and 2% increase in mortality (HR, 1.022; 95% CI, 1.020 to 1.023). Having ≥5 missing teeth substantially increased risk for cardiovascular outcomes, and even a small number of missing teeth (1 to 4) was associated with an increased risk for MI, stroke, and death. This association was consistent in subgroup analyses and especially strong among the younger subjects (age <65 y) and those with periodontitis. In this large Korean nationwide cohort study, we found that tooth loss showed a dose-dependent association with incident MI, HF, ischemic stroke, and all-cause death and was a good predictor of cardiovascular outcome. In clinical practice, the number of missing teeth can aid physicians in discriminating patients with a higher cardiovascular risk.