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Hypertension is a leading risk factor for cardiovascular events and death. Despite differences in clinical implications of hypertension between men and women, guidelines establishing optimal blood pressure (BP) targets are still debated. The aim of this study was to investigate sex differences in the BP level associated with increased risks of major adverse cardiac and cerebral events (MACCEs) among antihypertensive-treated patients. Using data from the Korean National Health Insurance Service-National Sample Cohort, we enrolled antihypertensive-treated patients and divided them into four categories: Group 1: SBP < 120 and DBP < 80 mm Hg; Group 2: 120 ≤ SBP < 130 and DBP < 80 mm Hg; Group 3: 130 ≤ SBP < 140 or 80 ≤ DBP < 90 mm Hg; and Group 4: SBP ≥ 140 or DBP ≥ 90 mm Hg. We performed time-dependent cox regression analysis to investigate sex differences in the BP levels that increased the risk of MACCEs. Most of the 98 267 patients fell into Group 3 (53.2% men and 52.8% women) and Group 4 (30.5% men and 28.1% women). During 8.34 ± 2.07 years, there were 8,813 MACCEs and 791 deaths. The incidences of MACCEs and death tended to increase as the BP increased in both sexes. Compared to Group 1, the risk of MACCEs significantly increased only in Group 4 for men, while it significantly increased in Groups 3 and 4 for women. This study shows that there are sex differences in the BP level at which the risk of MACCEs increases. Our finding suggests that sex should be significantly considered when determining the optimal BP target in patients undergoing hypertension treatment. [ABSTRACT FROM AUTHOR]

Objective: The risk of procedure-related complications and rhythm outcomes differ between men and women after atrial fibrillation catheter ablation (AFCA). We evaluated whether consistent sex differences existed in mapping and rhythm outcomes in repeat ablation procedures.Methods: Among 3282 patients in the registry, we analysed 443 consecutive patients (24.6% female, 58.5±10.3 years old, 61.5% with paroxysmal atrial fibrillation) who underwent a second AFCA. We compared the clinical factors, mapping, left atrial (LA) pressure, complications and long-term clinical recurrences after propensity score matching.Results: LA volume index (43.1±18.6 vs 35.8±11.6 mL/m2, p<0.001) was higher, but LA dimension (40.0±6.8 vs 41.6±6.3 mm, p=0.018), LA voltage (0.94±0.55 vs 1.20±0.68 mV, p=0.002) and pericardial fat volume (89.5±43.1 vs 122.1±53.9 cm3, p<0.001) were lower in women with repeat ablation than in their male counterparts. Pulmonary vein (PV) reconnections were lower (58.7% vs 74.9%, p=0.001), but the proportion of extra-PV triggers (27.5% vs 17.0%, p=0.026) and elevated LA pulse pressures (79.7% vs 63.7%, p=0.019) was significantly higher in women than in men. There was no significant sex difference in the rate of procedure-related complications (4.6% vs 4.2%, p=0.791). During a 31-month (8-60) median follow-up, clinical recurrences were significantly higher in women after both the de novo procedure (log-rank p=0.039, antiarrhythmic drug (AAD)-free log-rank p<0.001) and the second procedure (log-rank p=0.006, AAD-free log-rank p=0.093). Female sex (HR 1.51, 95% CI 1.06 to 2.15, p=0.023), non-paroxysmal atrial fibrillation (HR 1.78, 95% CI 1.30 to 2.34, p<0.010) and extra-PV triggers (HR 1.88, 95% CI 1.28 to 2.75, p=0.001) were independently associated with clinical recurrences after repeat procedures.Conclusions: During repeat AFCA procedures, PV reconnections were lower in women than in men, and the existence of extra-PV triggers and an LA pressure elevation were more significant, which resulted in poor rhythm outcomes.Trial Registration Number: NCT02138695. [ABSTRACT FROM AUTHOR]

Background: Some sea anemone toxins cause renal injuries resembling hemolytic uremic syndrome (HUS). To date, only a few cases of HUS caused by sea anemone stings have been reported. In this case report, we have described an HUS case caused by a sea anemone sting.Case Presentation: In November 2019, a 37-year-old man with no underlying disease was admitted to our hospital. He presented with intense pain, a rash on, and swelling in his right thigh. Two days prior, he had been stung by a sea anemone while scuba diving in Cebu, Philippines. His blood tests revealed renal dysfunction, and his platelet count was normal. However, on day three, the platelet count decreased rapidly. His blood haptoglobin level decreased, and schistocytes were identified on the peripheral blood smear. We suspected thrombotic microangiopathy and started the conventional treatment, comprising hemodialysis, blood transfusion, and antibiotic administration. ADAMTS-13 and genetic test results associated with atypical HUS were normal. Therefore, the patient was diagnosed with HUS caused by a sea anemone toxin.Conclusions: HUS caused by a sea anemone toxin is rare, but it is a serious medical disease. Clinicians should consider HUS in patients with such clinical presentations, and they should make prompt treatment-related decisions. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the effect of androgen suppression therapy (AST), comprising a 5-α reductase inhibitor (5-ARi) and androgen deprivation therapy (ADT), on the risk of bladder cancer incidence, recurrence, and mortality.Materials and Methods: We used the PRISMA statement to report the methods and results of this meta-analysis. Bladder cancer incidence, recurrence, and mortality after 5-ARi treatment and ADT were assessed using risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs). The protocol of this study is registered in the PROSPERO database (No. CRD42018118627).Results: We analyzed nine studies (n = 377,427) assessing the secondary effect of AST, with a mean follow-up period of 6 years (range, 2-13 years). Our result showed that the incidence of bladder cancer was significantly reduced when 5-ARi treatment (RR, 0.69; 95% CI, 0.58-0.81; I2 =0%) and ADT (HR, 0.81; 95% CI, 0.70-0.94; I2 =33%) were initiated before diagnosing bladder cancer. When treatment was initiated after diagnosing bladder cancer, 5-ARi treatment reduced cancer-specific mortality (RR, 0.29; 95% CI, 0.20-0.42; I2 =4.1%), whereas ADT reduced bladder cancer recurrence (HR, 0.30; 95% CI, 0.19-0.49; I2 =0%).Conclusions: This study corroborates that the use of 5-ARi and ADT could be helpful in managing bladder cancer and should not be limited to prostatic abnormalities. [ABSTRACT FROM AUTHOR]

Background and Purpose: Charcot-Marie-Tooth (CMT) disease is the most common hereditary peripheral neuropathy. CMT type 1A (CMT1A) accounts for approximately 50% of CMT patients and is linked to PMP22 gene duplication. Histone deacetylase-6 (HDAC6) has pleiotropic effects, such as regulating lipid homeostasis and cellular stress. Although HDAC6 has been regarded as a promising drug target for neurodegenerative diseases, its inhibition has not yet been tested in CMT1A. Here we have tested the therapeutic potential of CKD-504, a clinical stage HDAC6 inhibitor, in a mouse model of CMT1A EXPERIMENTAL APPROACH: The potency and selectivity of CKD-504 was evaluated, using a HDAC enzyme panel assay and western blots. The therapeutic potential of CKD-504 was evaluated using behavioural testing and electrophysiological assessments in the C22 mouse model of CMT1A. PMP22 protein expression and aggregation were analysed in mesenchymal stem cell-derived Schwann cells from CMT1A patients and sciatic nerves from C22 mice.Key Results: The HDAC6 inhibitor, CKD-504, modulated molecular chaperon proteins such as HSP90 and HSP70, which are involved in the folding/refolding of proteins such as PMP22. CKD-504 treatment restored myelination in both mesenchymal stem cell-derived Schwann cells from CMT1A patients and sciatic nerves of C22 mice and improved the axonal integrity of the sciatic nerve, leading to behavioural, electrophysiological, and histological improvements in C22 mice.Conclusion and Implications: A novel HDAC6 inhibitor, CKD-504, has potent therapeutic efficacy for CMT1A. [ABSTRACT FROM AUTHOR]

Background: The number of technology-dependent children (TDC) is increasing in South Korea, but available healthcare services after their discharge are poor. This study aimed to examine how TDC and caregivers live at home and identify their difficulties and needs regarding home care with few services to support them.Methods: This cross-sectional study was conducted in a tertiary hospital for children in South Korea. A self-reported questionnaire was completed by primary caregivers of TDC who were younger than 19 years and had been dependent on medical devices for more than 3 months. Technologies included home mechanical ventilation, oxygen supplementation, suction equipment, enteral feeding tube, and home total parenteral nutrition. Patterns of healthcare use and home care of TDC and caregivers' perception toward child were assessed.Results: A total of 74 primary caregivers of TDC completed a self-reported questionnaire. About 60% children were aged under 5 years. There were 31.1% children who required both respiratory and nutritional support. On average, caregivers took care of a child for 14.4 (±6.1) hours, slept for 5.6 (±1.6) hours, and spent 2.4 h per day on personal activities. Children used hospital services for 41.3 (±45.6) days in 6 months, and most (78.1%) were transported through private car/ambulance. Participants (75.6%) reported taking more than an hour to get to the hospital. More than 80% of caregivers responded that child care is physically very burdensome. The only statistically significant relationships was between economic status and financial burden (p = 0.026).Conclusions: Caregivers of TDC reported having significant time pressure regarding childcare-related tasks, insufficient time for personal activities, and inefficient hospital use because of inadequate medical services to support them in South Korea. Thus, it is necessary to support caregivers and develop a home care model based on current medical environment. [ABSTRACT FROM AUTHOR]

Background: Suicide is a major cause of death in many countries, and previous suicidal attempt is known to be the predictor of future suicide. Korea is considered one of the countries with the highest suicide rate among the Organisation for Economic Co-operation and Development (OECD) members for over a decade. We aimed to investigate the epidemiologic characteristics of hospitalised patients after suicidal acts in Korea.Methods: Data from the Korean National Hospital Discharge In-depth Injury Survey were analysed, and patients older than 9 years admitted to nationwide hospitals after suicidal acts from 2005 to 2016 were included. Their epidemiologic characteristics were explored, and we divided them into groups according to suicidal means (injury vs. poisoning) and treatment outcome (good vs. poor). The association of each characteristic with injury as suicidal means and with poor treatment outcome were explored.Results: The sample included 7609 patients (corresponding to 227,571 in national population). More patients were female than male, and most were in their 40s in both sexes. Hospitalisation rate peaked in patients older than 80 years for both sexes. Male and young patients aged 10-19 years and capital residents showed relatively higher odds of choosing injury as suicidal means. Males and patients aged 40-64 and ≥65 years showed relatively higher odds of poor treatment outcome.Limitations: Some suicide attempters were excluded from the survey such as those who did not visit a hospital after the suicide attempt.Conclusions: This epidemiologic feature of suicide attempters might serve as baseline data for preventive policies regarding suicide. [ABSTRACT FROM AUTHOR]

Objective: There are few studies on cerebral palsy (CP) in African children and our study aimed to describe the aetiology, characteristics and severity of CP in children from Nigeria.Design: A population-based study using key informant methodology (KIM) was conducted as part of a clinical research trial. Children aged 4-15 years were clinically assessed for CP.Results: The estimated prevalence of CP using KIM was 2.3/1000 children (95% CI 2.0 to 2.5/1000). 388 children were diagnosed with CP, with Gross Motor Function Classification System level 1 in 70 (18.1%), II in 156 (40.2%), III in 54 (13.9%), IV in 54 (13.9%), V in 54 (13.9%). 300/388 (77.3%) had Manual Ability Classification Scale of level 1-3 and 88 (22.7%) of level 4-5. CP types were spastic in 271 (70%), with 60% of these bilateral and 40% unilateral, ataxic 38 (9.8%), dystonic 18 (4.6%), choreoathetoid 29 (7.5%) and unclassifiable 32 (8.3%). Postneonatal risk factors for CP were seen in 140 (36.1%) children including malaria with seizures 101/140 (72.1%), malaria with coma 21/140 (15.0%), meningitis 12/140 (8.6%), tuberculosis 2/140 (1.4%), sickle cell disease 3/140 (2.2%), HIV 1/221 (0.7%). Prenatal/perinatal risk factors were seen in 248 (63.9%%), birth asphyxia 118 (47.6%) and clinical congenital rubella syndrome 8 (3.3%) and hyperbilirubinaemia 59 (23.8%) were identified as preventable risk factors for CP.Conclusion: The profile of CP in this population is similar to that found in other low-income and middle-income countries (LMIC). Some risk factors identified were preventable. Prevention and management strategies for CP designed for LMIC are needed. [ABSTRACT FROM AUTHOR]

Background: We postulated that the use of robotics may improve outcomes in hiatal hernia repair.Methods: We performed a retrospective analysis of a prospectively collected Society of Thoracic Surgery database at a single institution of patients who underwent elective hiatal hernia repair from 2012 to 2017 using either laparoscopy or the da Vinci Xi robot. We compared patient characteristics and outcomes and then performed univariate and multivariate logistic regression modeling to determine the factors associated with postoperative morbidity.Results: There were 293 consecutive patients who underwent elective hiatal hernia repair using either a laparoscopic (n = 151) or a robotic (n = 142) technique. There were no significant differences in age, gender, BMI, smoking history, presence of comorbidity, or hiatal hernia type. Seventy percent of the cases were a repair of either type III or type IV hiatal hernia. There were significantly higher ASA III and IV (7.9% vs. 4.2%, P = 0.03), higher Toupet fundoplication (83.4% vs. 44.4%, P < 0.001), and lower redo-repair (7.3% vs. 20.4%, P = 0.001) in the laparoscopic group compared to the robotic group. The hospital length of stay was significantly shorter (1.3 ± 1.8 vs. 1.8 ± 1.5 days, P = 0.003) and there were significantly lower rates of complications (6.3 vs. 19.2%, P = 0.001) after robotic compared to laparoscopic hiatal hernia repair. There was no difference in readmission rate and mortality. Multiple logistic regression analysis showed that older age and laparoscopic technique were associated with higher complications after surgery.Conclusion: The use of the Da Vinci Xi robot in our institution was associated with improved outcomes compared to laparoscopic hiatal hernia repair despite a higher incidence of re-operative cases in the robotic group. Thus, short-term outcomes of Da Vinci Xi robot-assisted hiatal hernia repair are not inferior to laparoscopic hiatal hernia repair. Further studies are needed to determine if Da Vinci Xi robot provides superior short-term and long-term outcome in treatment of symptomatic hiatal hernia. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is a lethal and highly vascular type of brain tumor. We previously reported that isolinderalactone enhances GBM apoptosis in vitro and in vivo, but its role in tumor angiogenesis is unknown. Here, we investigated the anti-angiogenic activity of isolinderalactone and its mechanisms. In a human GBM xenograft mouse model, isolinderalactone significantly reduced tumor growth and vessels. Isolinderalactone decreased the expression of vascular endothelial growth factor (VEGF) mRNA, protein, and VEGF secretion in hypoxic U-87 GBM cells and also in xenograft GMB tissue. In addition, we demonstrated that isolinderalactone significantly inhibited the proliferation, migration, and capillary-like tube formation of human brain microvascular endothelial cells (HBMECs) in the presence of VEGF. We also found that isolinderalactone decreased sprout diameter and length in a 3D microfluidic chip, and strongly reduced VEGF-triggered angiogenesis in vivo Matrigel plug assay. Isolinderalactone downregulated hypoxia-inducible factor-1α (HIF-1α) and HIF-2α proteins, decreased luciferase activity driven by the VEGF promoter in U-87 cells under hypoxic conditions, and suppressed VEGF-driven phosphorylation of VEGFR2 in HBMECs. Taken together, our results suggest that isolinderalactone is a promising candidate for GBM treatment through tumor angiogenesis inhibition. [ABSTRACT FROM AUTHOR]

Although lenalidomide plus dexamethasone (RD) is a therapeutic option for relapsed/refractory multiple myeloma (RRMM), limited real-world clinical data exist. The purpose of this study was to estimate efficacy and safety of RD in RRMM patients of the clinical practice. Data from patients at 25 university hospitals in South Korea between October 2009 and December 2016 were collected retrospectively. We report the effectiveness and safety of RD in 546 RRMM patients in routine clinical practice in South Korea. Patients (median age, 65 years) typically received median 7 cycles of RD, and 184 (33.7%) patients were treated with 10 or more cycles of RD. Patients with renal impairment (CLCr < 40 mL/min; 10.4%), comorbid conditions (≥ 2; 12.0%), and poor performance status (≥ 2; 25.1%) were included. The overall response rate was 64.2%: complete response (13.1%), very good partial response (VGPR 19.9%). With median follow-up duration of 18.6 months, median PFS and OS were 11.2 months and 25.2 months, respectively. In multivariate analysis, less than 2 comorbid conditions, normal LDH, failed one chemotherapy prior to RD, and ≥ 10 cycles of RD therapy had significantly prolonged PFS (P = 0.007, P = 0.011, P = 0.007, and P < 0.001, respectively). Adverse events were acceptable. RD is effective and safe in real-life clinical practice, including patients with comorbidities. RD is an effective and safe treatment in a real clinical setting which includes patients with comorbidities. Early and continual use of RD treatment may improve RRMM survival outcomes. [ABSTRACT FROM AUTHOR]

Background: Panic disorder (PD) is a prevalent and highly disabling mental condition. However, less is known about relationships between biomarkers that may together predict a better response to pharmacological treatment. The objective of the present study was to compare the brain white matter (WM) connectivity between treatment-responsive patients with panic disorder (RPD) and non-responsive patients with panic disorder (NRPD) after 12 weeks of pharmacotherapy.Methods: Sixty-four patients with PD were enrolled in this study (RPD, n = 37; NRPD, n = 27). All patients were examined by using magnetic resonance imaging at 3 Tesla. The Panic Disorder Severity Scale (PDSS), Albany Panic and Phobia Questionnaire (APPQ), Anxiety Sensitivity Inventory-Revised (ASI-R), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI) were administered at baseline of the study. Fractional anisotropy (FA) data were compared using tract-based spatial statistics (TBSS).Results: TBSS results showed that the FA values of the patients with NRPD were significantly higher than of those with RPD in the WM regions such as the precentral gyrus, parahippocampal gyrus, posterior corona radiata, posterior thalamic radiation, posterior parts of the corpus callosum, and precuneus. Symptom severity scales, such as ASI-R scores, showed significant positive correlations of the FA values with the fronto-temporal WM regions in NRPD.Conclusions: These results suggest that structural changes to areas such as the fronto-limbic regions and the posterior part of default mode network, could influence medication response in PD. Further studies with a larger number of patients should be performed to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: The association between diabetes mellitus (DM) and bone diseases is acknowledged. However, the mechanistic pathways leading to the alveolar bone (AB) destruction remain unclear. This study aims to elucidate the mechanical forces (MF)-induced AB destruction in DM and its underlying mechanism.Methods: In vivo periodontal tissue responses to MF were evaluated in rats with diabetes. In vitro human periodontal ligament (PDL) cells were either treated with advanced glycation end products (AGEs) alone or with AGEs and MF.Results: In vivo, the transcription of VEGF-A, colony stimulating factor-1 (CSF-1), and Ager was upregulated in diabetes, whereas changes in DDOST and Glo1 mRNAs were negligible. DM induced VEGF-A protein in the vascular cells of the PDL and subsequent angiogenesis, but DM itself did not induce osteoclastogenesis. MF-induced AB resorption was augmented in DM, and such augmentation was morphologically substantiated by the occasional undermining resorption as well as the frontal resorption of the AB by osteoclasts. The mRNA levels of CSF-1 and vascular endothelial growth factor (VEGF) during MF application were highly elevated in diabetes, compared with those of the normal counterparts. In vitro, AGEs treatment elevated Glut-1 and CSF-1 mRNA levels via the p38 and JNK pathways, whereas OGT and VEGF levels remained unchanged. Compressive MF especially caused upregulation of VEGF, CSF-1, and Glut-1 levels, and such upregulation was further enhanced by AGEs treatment.Conclusions: Overloaded MF and AGEs metabolites may synergistically aggravate AB destruction by upregulating CSF-1 and VEGF. Therefore, regulating the compressive overloading of teeth, as well as the levels of diabetic AGEs, may prove to be an effective therapeutic modality for managing DM-induced AB destruction. [ABSTRACT FROM AUTHOR]

Background: Post-laparoscopic shoulder pain (PLSP) frequently follows a laparoscopic cholecystectomy. A proposed mechanism for PLSP is the irritation or injury of the phrenic nerve by the CO2 pneumoperitoneum during laparoscopic surgery. Here, we investigated whether a phrenic nerve block (PNB), performed under ultrasound guidance, could reduce the incidence and severity of PLSP after laparoscopic cholecystectomy.Method: Sixty patients were randomized into two groups, with one group receiving PNB with 4 ml (30 mg) of 0.75% ropivacaine (group P, n = 28) and a control group (group C, n = 32). The existence and severity of PLSP were assessed for 2 days postoperatively. A pulmonary function test (PFT) and diaphragmatic excursion test were performed pre- and postoperatively.Results: With ultrasound guidance, all PNBs were performed successfully in group P. In group P, the overall incidence and severity of PLSP decreased significantly. There were no significant differences in incisional pain, visceral pain, and analgesic requirements between the groups. Right-side diaphragmatic excursion decreased significantly in group P at 1 h postoperatively. The PFT results and respiratory discomfort assessed by a modified Borg's scale were not different significantly between the groups.Conclusion: Based on these findings, ultrasound-guided PNB can prevent or reduce the PLSP without clinically significant respiratory discomfort. [ABSTRACT FROM AUTHOR]

Background: Robotic modified radical neck dissection (MRND) using a gasless transaxillary approach has been reported to be a safe and meticulous technique in patients with papillary thyroid carcinoma (PTC) and lateral neck node metastasis (N1b). Few studies, however, have attempted to assess the long-term oncologic outcomes of robotic MRND in these patients. This study aimed to compare perioperative and 5-year oncologic outcomes of robotic MRND with conventional open procedures in patients with N1b PTC.Methods: Between September 2007 and February 2010, 193 patients with N1b PTC underwent total thyroidectomy and MRND by a single surgeon. Of these, 42 (21.8 %) underwent robotic procedures and 151 (78.2 %) underwent conventional open procedures. All patients received 3.7- to 5.5-GBq radioactive iodine (RAI) ablation, post-therapy whole-body scans (TxWBSs), and diagnostic WBS (DxWBSs) during follow-up. An exact 1:3 matching for age and stage was performed to minimize selection bias, and perioperative and 5-year oncologic outcomes were compared in the matched groups.Results: The mean follow-up period was 66.0 months (range 60-90 months). Number of retrieved cervical lymph nodes (LNs) (p = .102) and postoperative ablation success rates (p = .864) were similar between the two groups. TSH-suppressed serum Tg concentrations after 5 years (0.7 ± 1.5 vs. 2.4 ± 14.1 ng/ml; p = .471) and recurrence rates in the robotic and open groups (1/41 [2.4 %] vs. 3/102 [2.9 %]; p = .864) were similar for the 5-year follow-up period. Four patients experienced recurrence: Three exhibited regional lymph node metastasis, and one showed bilateral lung metastases.Conclusion: The perioperative and 5-year oncologic outcomes were similar after robotic and conventional open MRND. Large, prospective randomized controlled trials with long-term follow-up data are needed to validate these results. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the diagnostic performance of breast magnetic resonance imaging (MRI) in preoperative evaluation of axillary lymph node metastasis (ALNM) in breast cancer patients and to assess whether breast MRI can be used to exclude advanced nodal disease.Methods: A total of 425 patients were included in this study and breast MRI findings were retrospectively reviewed. The diagnostic performance of breast MRI for diagnosis of ALNM was evaluated in all patients, patients with neoadjuvant chemotherapy (NAC), and those without NAC (no-NAC). We evaluated whether negative MRI findings (cN0) can exclude advanced nodal disease (pN2-pN3) using the negative predictive value (NPV) in each group.Results: The sensitivity and NPV of breast MRI in evaluation of ALNM was 51.3 % (60/117) and 83.3 % (284/341), respectively. For cN0 cases on MRI, pN2-pN3 manifested in 1.8 % (6/341) of the overall patients, 0.4 % (1/257) of the no-NAC group, and 6 % (5/84) of the NAC group. The NPV of negative MRI findings for exclusion of pN2-pN3 was higher for the no-NAC group than for the NAC group (99.6 % vs. 94.0 %, p = 0.039).Conclusions: Negative MRI findings (cN0) can exclude the presence of advanced nodal disease with an NPV of 99.6 % in the no-NAC group.Key Points: • Breast MRI can be used to exclude advanced nodal disease (pN2-3). • Negative MRI allows breast cancer patients to avoid unnecessary axillary surgery (98.2 %). • Negative MRI findings exclude 99.6 % of pN2-pN3 in the no-NAC group. • Negative MRI findings exclude 96.0 % of pN2-pN3 in the NAC group. [ABSTRACT FROM AUTHOR]

Diet-induced weight loss and regain leads to physiological and metabolic changes, some of which are potentially harmful. However, the specific metabolic processes and dysfunctions associated with weight regain, and how they differ from initial weight gain, remain unclear. Thus, we examined the metabolic profiles of mice following weight regain compared to initial weight gain. Mice were fed a normal diet or a high-fat diet or were cycled between the two diets to alternate between obese and lean states. Liver samples were collected and hepatic metabolites were profiled using nuclear magnetic resonance (NMR). The identified metabolites associated with weight regain were quantified using gas chromatography/mass spectrometry (GC/MS) and lipid profiles were assessed using ultra-high-performance liquid chromatography-quadrupole time-of-flight MS (UPLC-QTOF-MS). In addition, changes in expression of pro-inflammatory cytokines and gluconeogenic enzymes were investigated using polymerase chain reaction (PCR) and western blotting, respectively. Hepatic levels of several amino acids were reduced in mice during weight regain compared with initial weight gain. In addition, gluconeogenic enzyme levels were increased following weight regain, indicating an up-regulation of gluconeogenesis. Lipidomic profiling revealed that levels of ceramide and sphingomyelin, which are related to obesity-induced inflammation, were significantly increased during weight regain compared to initial weight gain. Moreover, tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) levels were significantly up-regulated during weight regain. In this study, weight regains lead to an up-regulation of gluconeogenesis and aggravated inflammation. Additionally, weight regain can worsen the metabolic dysfunction associated with obesity. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy of butterfly inlay cartilage tympanoplasty and compare it with conventional underlay cartilage tympanoplasty in terms of success rate and hearing outcomes.Materials and Methods: The study included 35 patients (36 ears) who underwent butterfly inlay cartilage tympanoplasty (inlay group, 23 ears of 22 patients) or conventional underlay cartilage tympanoplasty (underlay group, 13 ears). The anatomical success rate and hearing outcomes were analysed.Results: Re-perforation occurred in 2 cases (8.7%) in the inlay group and 3 (23.1%) in the underlay group. One patient in the inlay group developed a serious infection, and one in the underlay group developed massive granulation of the tympanic membrane. In the inlay group, the air-bone gap (ABG) decreased from 19.9 (±12.6) dB HL preoperatively to 13.8 (±11.3) dB HL postoperatively (p=0.047), in the underlay group, it decreased from 23.5 (±15.8) dB HL to 18.3 (±20.6) dB HL. Regarding improvement in ABG, the difference between the group was not statistically significant (p=0.968).Conclusion: Butterfly inlay cartilage tympanoplasty is comparable with conventional underlay cartilage tympanoplasty in both anatomic and audiological success rates. Owing to its simplicity, shorter operation time, and rapid patient recovery, butterfly inlay cartilage tympanoplasty could be considered a favourable surgical option. [ABSTRACT FROM AUTHOR]

Background: Three-dimensional (3D) imaging for laparoscopy was introduced to overcome the limitations of conventional two-dimensional (2D) imaging that lacked depth perception and spatial orientation. This study aimed to evaluate the effect of 3D imaging in laparoscopic colectomy with D3 lymphadenectomy for colon cancer.Methods: From February 2014 to October 2016, the prospective database of 278 consecutive patients with colon cancer was analyzed retrospectively; these patients underwent laparoscopic surgery with 2D (n = 111) and 3D (n = 167) imaging, with curative intent.Results: No difference was found in sex, body mass index, history of abdominal surgery, and American Society of Anesthesiologists grade between the 3D and 2D groups. The estimated blood loss was less in the 3D group than in the 2D group (50 mL [30-100 mL] versus 100 mL [50-100 mL], P < .001). The number of resected lymph nodes was higher in the 3D group (n = 47 [37.5-60] versus 41 [32-51.5], P = .001). However, a difference in operative time was not observed in both groups (150 minutes [125-175 minutes] versus 155 minutes [135-177.5 minutes], P = .186). Postoperative morbidity was similar in both groups (7.8% versus 8.1%, P = 1.000). Time to pass first flatus (3 days [2-4 days] versus 3 days [3-4 days], P = .746) and postoperative hospital stay (6 days [6-8 days] versus 6 days [6-7 days], P = .087) were also similar.Conclusions: This study shows that laparoscopic colectomy with D3 lymphadenectomy for colon cancer using 3D laparoscopic systems appears to be beneficial, with less blood loss, which should be addressed in prospective studies. [ABSTRACT FROM AUTHOR]

Objectives: Hyponatraemia is a well-known predictor of clinical outcomes in heart failure (HF). However, the mechanism remains poorly understood. Previous reports suggest that hyponatraemia is related to right HF. We sought to evaluate the association between right ventricular (RV) dysfunction and hyponatraemia, and the impact of this relationship on the prognosis of patients with acute heart failure (AHF).Methods: This is a nested case-control study of the Korean Acute Heart Failure registry. Among 2935 AHF patients enrolled prospectively and consecutively at four tertiary hospitals in Korea from 2011 to 2014, 116 patients with severe persistent hyponatraemia, defined as serum sodium level <130 mmol/L at admission and <135 mmol/L before discharge, were matched with 232 controls, based on propensity scores for hyponatraemia. RV function was assessed with fractional area change (FAC) by echocardiography.Results: RV dysfunction (FAC <35%) was more prevalent in patients with severe persistent hyponatraemia than in those without (81.0% vs 33.6%, p<0.001). Hyponatraemia was strongly associated with RV dysfunction (adjusted OR 8.00, 95% CI 4.50 to 14.22, p<0.001), but not with left ventricular dysfunction (adjusted OR 1.21, 95% CI 0.74 to 1.50, p=0.308). RV dysfunction was an independent predictor of all-cause mortality, after adjustment for hyponatraemia (adjusted HR 2.20, 95% CI 1.53 to 3.15, p<0.001), while hyponatraemia was not (adjusted HR 1.33, 95% CI 0.94 to 1.87, p=0.108).Conclusions: In patients with AHF, hyponatraemia was more common with RV dysfunction. RV dysfunction, rather than hyponatraemia, was more significantly related with patients' prognosis. Thus, the utility of RV dysfunction instead of hyponatraemia per se should be considered in HF risk models.Trial Registration Number: Korean Acute Heart Failure registry NCT01389843; Results. [ABSTRACT FROM AUTHOR]

We aimed to clarify the key factor determining the effect of beta blocker attenuating high fat diet- induced obesity and bone loss. Six-week-old C57BL/6 male mice were assigned to groups reflecting different relative onset of obesity and beta blocker administration, different diet (control vs. high fat), and treatment (vehicle vs. beta blocker: propranolol). Mice in Group 1 were fed a control diet (CON) or high fat diet (HIGH) with vehicle or propranolol for 12 weeks. Mice in Group 2 were fed a CON or HIGH without pharmaceutical treatment for the first 12 weeks, followed by another 12 weeks of treatment with vehicle or propranolol. Mice in Group 3 were fed a CON without pharmaceutical treatment for the first 12 weeks, followed by stratification into diet-based subgroups and another 12 weeks of treatment with vehicle or propranolol. Propranolol attenuated the HIGH-induced increase in body weight/fat mass in Group 1 mice and in Group 3 mice, but not in Group 2 mice. Propranolol mitigated HIGH-induced reduction in femoral trabecular bone mineral density and bone architecture deterioration in Group 1 mice but not in Group 2 mice. HIGH feeding in Group 3 did not compromise skeletal integrity. Taken together, propranolol attenuates HIGH-induced body weight increases while weight gain is in progress but not once obesity has already been established. HIGH feeding during the growth period results in compromised bone mass/architecture; which can be attenuated by propranolol administration during the growth period, but not by propranolol administration after obesity has already been established. [ABSTRACT FROM AUTHOR]

Background: Transanal total mesorectal excision (taTME) is expected to provide benefits in the removal of the complete mesorectum for low rectal lesions, and several clinical studies regarding this technique have been reported. However, a transanal platform has not yet been standardized, and diverse transanal endoluminal surgery access devices have been used, based on individual surgeon preferences. In the present study, we performed laparoscopy-assisted taTME in cadavers and compared the characteristics of four different platforms.Methods: Between January 2013 and April 2015, laparoscopy-assisted taTME was performed on six fresh cadavers. Flexible [SILS™ Port (Covidien), GelPOINT(®) Path Transanal Access Platform (Applied Medical)] and rigid [TEO(®) (Karl Storz Endoskope), TEM (Richard Wolf)] transanal access platforms were used on three cadavers each.Results: All cadavers were male, with a mean age of 69.2 (range 57-86) years. The mean operation time was 146.3 (range 140-155) min with flexible platforms and 206.7 (range 150-260) min with rigid platforms. The mean specimen length was 23 (range 18-26) cm. Complete or nearly complete mesorectal specimens were obtained in all cases, except for one case using the TEM platform. Flexible platforms (SILS and GelPOINT) provided a short set-up time, relatively atraumatic retraction, and easy application of familiar laparoscopic instruments; a narrow operative field was its limitation. The rigid platforms (TEO and TEM) enabled larger and more stable operative fields and space than did the SILS platform, but they were limited by a narrow view, prolonged set-up time, rigidity, and long channels relative to the short distance from the anus to the rectal closure site.Conclusion: In this preliminary study, laparoscopy-assisted taTME was a feasible and safe procedure using both rigid and soft platforms, despite some limitations of each platform. [ABSTRACT FROM AUTHOR]

Importance: Depression has been associated with poorer medical outcomes in acute coronary syndrome (ACS), but there are few data on the effects of antidepressant treatment on long-term prognosis.Objective: To investigate the effect on long-term major adverse cardiac events (MACE) of escitalopram treatment of depression in patients with recent ACS.Design, Setting, and Participants: Randomized, double-blind, placebo-controlled trial conducted among 300 patients with recent ACS and depression enrolled from May 2007 to March 2013, with follow-up completed in June 2017, at Chonnam National University Hospital, Gwangju, South Korea.Interventions: Patients were randomly assigned to receive either escitalopram in flexible dosages of 5, 10, 15, or 20 mg/d (n = 149) or matched placebo (n = 151) for 24 weeks.Main Outcomes and Measures: The primary outcome was MACE, a composite of all-cause mortality, myocardial infarction (MI), and percutaneous coronary intervention (PCI). Four secondary outcomes were the individual MACE components of all-cause mortality, cardiac death, MI, and PCI. Cox proportional hazards models were used to compare the escitalopram and placebo groups by time to first MACE.Results: Among 300 randomized patients (mean age, 60 years; 119 women [39.3%]), 100% completed a median of 8.1 (interquartile range, 7.5-9.0) years of follow-up. MACE occurred in 61 patients (40.9%) receiving escitalopram and in 81 (53.6%) receiving placebo (hazard ratio [HR], 0.69; 95% CI, 0.49-0.96; P = .03). Comparing individual MACE outcomes between the escitalopram and placebo groups, respectively, incidences for all-cause mortality were 20.8% vs 24.5% (HR, 0.82; 95% CI, 0.51-1.33; P = .43), for cardiac death, 10.7% vs 13.2% (HR, 0.79; 95% CI, 0.41-1.52; P = .48); for MI, 8.7% vs 15.2% (HR, 0.54; 95% CI, 0.27-0.96; P = .04), and for PCI, 12.8% vs 19.9% (HR, 0.58; 95% CI, 0.33-1.04; P = .07).Conclusions and Relevance: Among patients with depression following recent acute coronary syndrome, 24-week treatment with escitalopram compared with placebo resulted in a lower risk of major adverse cardiac events after a median of 8.1 years. Further research is needed to assess the generalizability of these findings.Trial Registration: ClinicalTrials.gov Identifier: NCT00419471. [ABSTRACT FROM AUTHOR]

Background: Metastasis is the main cause of death for lung cancer patients. The ex vivo 4D acellular lung model has been shown to mimic this metastatic process. However, the main concern is the model's lack of cellular components of the tumor's microenvironment. In this study, we aim to determine if the intact lung microenvironment will still allow lung cancer metastasis to form.Methods: We harvested a heart-lung block from a rat and placed it in a bioreactor after cannulating the pulmonary artery, trachea and tying the right main bronchus for 10-15 days without any tumor cells as a control group or with NSCLC (A549, H1299 or H460), SCLC (H69, H446 or SHP77) or breast cancer cell lines (MCF7 or MDAMB231) through the trachea. We performed lobectomy, H&E staining and IHC for human mitochondria to determine the primary tumor's growth and formation of metastatic lesions. In addition, we isolated circulating tumor cells (CTC) from the model seeded with GFP tagged cells.Results: In the control group, no gross tumor nodules were found, H&E staining showed hyperplastic cells and IHC showed no staining for human mitochondria. All of the models seeded with cancer cell lines formed gross primary tumor nodules that had microscopic characteristics of human cancer cells on H&E staining with IHC showing staining for human mitochondria. CTC were isolated for those cells labeled with GFP and they were viable in culture. Finally, all cell lines formed metastatic lesions with cells stained for human mitochondria.Conclusion: The cellular ex vivo 4D model shows that human cancer cells can form a primary tumor, CTC and metastatic lesions in an intact cellular environment. This study suggests that the natural matrix scaffold is the only necessary component to drive metastatic progression and that cellular components play a role in modulating tumor progression. [ABSTRACT FROM AUTHOR]

Background: Primary laparoscopic hiatal repair with fundoplication is associated with a high recurrence rate. We wanted to evaluate the potential risks posed by routine use of onlay-mesh during hiatal closure, when compared to primary repair.Methods: Utilizing single-institutional database, we identified patients who underwent primary laparoscopic hiatal repair from January 2005 through December 2014. Retrospective chart review was performed to determine perioperative morbidity and mortality. Long-term results were assessed by sending out a questionnaire. Results were tabulated and patients were divided into 2 groups: fundoplication with hiatal closure + absorbable or non-absorbable mesh and fundoplication with hiatal closure alone.Results: A total of 505 patients underwent primary laparoscopic fundoplication. Mesh reinforcement was used in 270 patients (53.5%). There was no significant difference in the 30-day perioperative outcomes between the 2 groups. No clinically apparent erosions were noted and no mesh required removal. Standard questionnaire was sent to 475 patients; 174 (36.6%) patients responded with a median follow-up of 4.29 years. Once again, no difference was noted between the 2 groups in terms of dysphagia, heartburn, long-term antacid use, or patient satisfaction. Of these, 15 patients (16.9%, 15/89) in the 'Mesh' cohort had symptomatic recurrence as compared to 19 patients (22.4%, 19/85) in the 'No Mesh' cohort (p = 0.362). A reoperation was necessary in 6 patients (6.7%) in the 'Mesh' cohort as compared to 3 patients (3.5%) in the 'No Mesh' cohort (p = 0.543).Conclusions: Onlay-mesh use in laparoscopic hiatal repair with fundoplication is safe and has similar short and long-term results as primary repair. [ABSTRACT FROM AUTHOR]

There is growing public interest in alternative approaches to addiction treatment and scientific interest in elucidating the neurobiological underpinnings of acupuncture. Our previous studies showed that acupuncture at a specific Shenmen (HT7) points reduced dopamine (DA) release in the nucleus accumbens (NAc) induced by drugs of abuse. The present study was carried out to evaluate the effects of HT7 acupuncture on γ-aminobutyric acid (GABA) neuronal activity in the ventral tegmental area (VTA) and the reinstatement of cocaine-seeking behavior. Using microdialysis and in vivo single-unit electrophysiology, we evaluated the effects of HT7 acupuncture on VTA GABA and NAc DA release and VTA GABA neuronal activity in rats. Using a within-session reinstatement paradigm in rats self-administering cocaine, we evaluated the effects of HT7 stimulation on cocaine-primed reinstatement. Acupuncture at HT7 significantly reduced cocaine suppression of GABA release and GABA neuron firing rates in the VTA. HT7 acupuncture attenuated cocaine-primed reinstatement, which was blocked by VTA infusions of the selective GABAB receptor antagonist 2-hydroxysaclofen. HT7 stimulation significantly decreased acute cocaine-induced DA release in the NAc, which was also blocked by 2-hydroxysaclofen. HT7 acupuncture also attenuated cocaine-induced sensitization of extracellular DA levels in the NAc. Moreover, HT7 acupuncture reduced both locomotor activity and neuronal activation in the NAc induced by acute cocaine in a needle-penetration depth-dependent fashion. These results suggest that acupuncture may suppress cocaine-induced DA release in the NAc and cocaine-seeking behavior through activation of VTA GABA neurons. Acupuncture may be an effective therapy to reduce cocaine relapse by enhancing GABAergic inhibition in the VTA. [ABSTRACT FROM AUTHOR]

Background: We evaluated the diagnostic usefulness of polymerase chain reaction (PCR) analysis for detecting varicella-zoster virus (VZV) infection and reactivation of VZV, using DNA extracted from saliva and plasma specimens obtained from subjects with suspected herpes zoster and from healthy volunteers during stressful and nonstressful conditions.Methods: There were 52 patients with a diagnosis of herpes zoster (group 1), 30 with a diagnosis of zoster-mimicking disease (group 2), and 27 healthy volunteers (group 3). Saliva and plasma samples were evaluated for VZV DNA by real-time PCR analysis.Results: Among patients with suspected herpes zoster (ie, patients in groups 1 and 2), the sensitivity of PCR analysis of salivary DNA for detecting VZV (88%; 95% confidence interval [CI], 74%-95%) was significantly higher than that of PCR analysis of plasma DNA (28%; 95% CI, 16%-44%; P < .001), whereas the specificity of PCR analysis of salivary DNA (100%; 95% CI, 88%-100%) was similar to that of PCR analysis of plasma DNA (100%; 95% CI, 78%-100%; P > .99). VZV DNA was not detected in saliva and plasma samples from group 3 (0%; 95% CI, 0%-14%).Conclusions: Real-time PCR analysis of salivary DNA is more sensitive than that of plasma DNA for detecting VZV among patients with suspected herpes zoster. We found no subclinical reactivation of VZV in group 3 following exposure to common stressful conditions. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to determine prognostic factors influencing outcomes of surgical treatment in patients with T4a hypopharyngeal cancer.Methods: The present study enrolled 93 patients diagnosed with T4a hypopharyngeal cancer who underwent primary surgery between January 2005 and December 2015 at six medical centers in Korea. Primary tumor sites included pyriform sinus in 71 patients, posterior pharyngeal wall in 14 patients, and postcricoid region in 8 patients. Seventy-two patients received postoperative radio(chemo)therapy.Results: Five-year disease-free survival (DFS) and disease-specific survival (DSS) rates were 38% and 45%, respectively. In univariate analysis, 5-year DFS was found to have significant and positive correlations with margin involvement (p < 0.001) and extracapsular spread (p = 0.025). Multivariate analysis confirmed that margin involvement (hazard ratio (HR): 2.81; 95% confidence interval (CI): 1.49-5.30; p = 0.001) and extracapsular spread (HR: 2.08; 95% CI: 1.08-3.99; p = 0.028) were significant factors associated with 5-year DFS. In univariate analysis, cervical lymph node metastasis (p = 0.048), lymphovascular invasion (p = 0.041), extracapsular spread (p = 0.015), and esophageal invasion (p = 0.033) were significant factors associated with 5-year DSS. In multivariate analysis, extracapsular spread (HR: 2.98; 95% CI: 1.39-6.42; p = 0.005) and esophageal invasion (HR: 2.87; 95% CI: 1.38-5.98; p = 0.005) remained significant factors associated with 5-year DSS.Conclusion: Margin involvement and extracapsular spread are factors influencing recurrence while extracapsular spread and esophageal invasion are factors affecting survival in patients with T4a hypopharyngeal cancer treated by primary surgery. [ABSTRACT FROM AUTHOR]

Background: Many studies advocate hormonal treatments including high-dose oral prednisolone as an effective treatment for epileptic spasms. However, little is known about the effects of intravenous methylprednisolone pulse therapy on infantile spasms. We investigated the short-term response to intravenous methylprednisolone pulse therapy for the treatment of infantile spasms.Methods: Patients with newly diagnosed infantile spasms and hypsarrhythmia on electroencephalography (EEG) at two tertiary centers in Korea were included. Patients received intravenous infusions of 30 mg/kg/day methylprednisolone for three days with tapering doses of oral prednisolone for two to four weeks for the treatment of infantile spasms. Response to methylprednisolone pulse therapy was evaluated by seizure frequency and follow-up EEG within three weeks.Results: Fourteen patients were sudied. The mean age at the onset of spasms was 7.0 months (range, 2.0 to 11.0 months). Etiological factors included structural abnormalities (N = 11), chromosomal anomaly (N = 1), and unknown (N = 2). Nine of 14 participants (64.3%) demonstrated complete freedom from spasm and resolution of hypsarrhythmia on EEG within 3 weeks; however, only five of nine responders (55.5%) remained free of spasms after the discontinuation of oral steroids. Adverse effects, including irritability or infection, were observed in four patients but were tolerable in all.Conclusions: Short-term methylprednisolone pulse therapy for the treatment of infantile spasms or hypsarrhythmia demonstrated rapid improvement in EEG and cessation of spasms without serious adverse effects. Further studies are needed to determine the long-term effects of spasm control. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the efficacy of a high dose of oral tegafur-uracil (400 mg/m2) plus leucovorin with preoperative chemoradiation of locally advanced rectal cancer and to explore the impact of polymorphisms of cytochrome P 2A6 (CYP2A6), uridine monophosphate synthetase (UMPS), and ATP-binding cassette B1 (ABCB1) on clinical outcome.Methods: Patients with cT3 or cT4 rectal cancer were enrolled and were given tegafur-uracil 400 mg/m2/day and leucovorin 90 mg/m2/day for 7 days a week during preoperative chemoradiation (50.4 Gy/28 fractions) in this phase II trial. Primary endpoint was pathologic complete response rate, and the secondary endpoint was to explore the association between clinical outcomes and genetic polymorphisms CYP2A6 (*4, *7, *9 and *10), UMPS G638C, and three ABCB1 genotypes (C1236T, C3435T, and G2677T).Results: Ninety-one patients were given study treatment, and 90 underwent surgery. Pathologic complete response was noted in 10 patients (11.1%). There was no grade 4 or 5 toxicity; 20 (22.0%) experienced grade 3 toxicities, including diarrhea (10, 11.0%), abdominal pain (2, 2.2%), and anemia (2, 2.2%). Relapse-free survival and overall survival at 5 years were 88.6% and 94.2%, respectively. Patients with the UMPS 638 CC genotype experienced significantly more frequent grade 2 or 3 diarrhea (p for trend = 0.018).Conclusions: Preoperative chemoradiation with tegafur-uracil 400 mg/m2/day with leucovorin was feasible, but did not meet the expected pathologic complete response rate. The UMPS 638 CC genotype might be a candidate biomarker predicting toxicity in patients receiving tegafur-uracil/leucovorin-based preoperative chemoradiation for locally advanced rectal cancer.Trial Registration: ISRCTN11812525 , registered on 25 July 2016. Retrospectively registered. [ABSTRACT FROM AUTHOR]

The Quality of Life Scale (QLS) is a frequently used semistructured interview for the assessment of functional outcomes in schizophrenia. Despite the use of the QLS for over 30years, the original 4-factor structure of the instrument (Interpersonal Relations, Instrumental Role, Intrapsychic Foundations, and Common Objects and Activities) has not been rigorously examined. Exploratory factor analyses (EFAs) and confirmatory factor analyses (CFAs) were used to evaluate the factor structure of the QLS in two independent datasets, including a mixed diagnostic sample of multi-episode participants (N=247), and a sample of individuals with a first episode of psychosis (N=337). A CFA with the first dataset indicated a poor fit for the 4-factor model of the QLS. Subsequent EFAs on this dataset led to a more promising 3-factor solution including 16/21 of the QLS items, which were similar to the first 3 of 4 factors originally proposed for the QLS. CFAs on the same dataset indicated that the 3-factor model for the QLS-Revised (QLS-R) fit the data well. This factor structure was evaluated with the second dataset using CFA and was also found to be fit the data well. The results support the robustness of the 3-factor model of the QLS-R in schizophrenia and mixed diagnostic samples. Future research should evaluate the validity of the 3-factor model of the QLS-R, and consider the merits of changing the name of the Intrapsychic Foundations factor to Motivation. [ABSTRACT FROM AUTHOR]

Background: Cytopenia occurs frequently during cytotoxic chemotherapy. Little is known about the optimal timing of influenza vaccination for patients receiving chemotherapy. This study compared the immunogenicity of an influenza vaccine administered concurrently with chemotherapy (day 1) and within the cytopenic period (day 11) during 3-week cytotoxic chemotherapy cycles.Methods: Adult patients with solid cancer undergoing scheduled 3-week cytotoxic chemotherapy were randomly assigned to receive the 2014-2015 seasonal influenza vaccine on day 1 or 11 during the chemotherapy cycle. Patients were stratified by their age (<60 and ≥60 years) and previous influenza vaccination status. Antibody responses to influenza vaccine strains H1N1, H3N2, and B were measured before and 21 to 28 days after vaccination with a hemagglutination inhibition antibody assay.Results: Ninety-seven patients were randomized into a day 1 group (n = 43) or a day 11 group (n = 54). Eighty-three patients were included in the final analysis. The mean age was 54 (± 11) years. Cancer types included breast (61%) and lung cancer (30%). Baseline characteristics were not significantly different between the groups. Seroprotection rates after vaccination were also not significantly different for the day 1 and 11 groups (strain H1N1, 67% vs 75% [P = .403]; strain H3N2, 77% vs 80% [P = .772]; strain B, 21% vs 27% [P = .472]). Seroconversion rates and postvaccination geometric mean titers were also similar for the groups. Vaccine-related adverse events were more common in the day 11 group (13% vs. 32%; P = .040).Conclusions: The antibody responses to influenza vaccination on days 1 and 11 during a 3-week cytotoxic chemotherapy cycle were comparable. Influenza vaccination can be performed concurrently with cytotoxic chemotherapy or during the cytopenic period. Cancer 2017;123:841-48. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Identification of early clinical markers that predict later treatment outcomes in first-episode psychosis is highly valuable. The present study was conducted to determine the best time at which to predict the late treatment response in first-episode psychosis patients treated with paliperidone extended release (ER), the factors predicting early treatment responses (at Week 2 and Week 3) and the relationships between the paliperidone ER plasma concentrations at Week 2 and Week 3, and the treatment responses at Week 2, Week 3 and Week 8. Various criteria for assessing treatment response were employed. We determined the plasma paliperidone concentrations at Week 2 and Week 3, using validated high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS). The treatment response at Week 3 optimally predicted the later (Week 8) response, in terms of negative predictive value (NPV). Independent predictors for good treatment responses at Week 2 and Week 3 were: Female gender, a higher educational level, a higher Positive and Negative Syndrome Scale (PANSS) excited score, and/or a shorter duration of untreated psychosis (DUP). The plasma paliperidone concentration at Week 3, but not Week 2, was a significant predictor of the late treatment response at Week 8. These results may help appropriate clinical decision-making for early non-responders after having their first episode of psychosis. [ABSTRACT FROM AUTHOR]

Background: Postoperative pancreatic fistula remains a troublesome complication after pancreatoduodenectomy (PD), and many authors have suggested factors that affect pancreatic leakage after PD. The International Study Group on Pancreatic Fistula (ISGPF) published a classification, but the new criteria adopted have not been substantially validated. The aims of this study were to validate the ISGPF classification and to analyze the risk factors of pancreatic leakage after duct-to-mucosa pancreatojejunostomy by a single surgeon.Methods: All patient data were entered prospectively into a database. The risk factors for pancreatic fistula were analyzed retrospectively for 247 consecutive patients who underwent conventional pancreatoduodenectomy or pylorus-preserving pancreatoduodenectomy between June 2005 and March 2009 at the Samsung Medical Center by a single surgeon. Duct-to-mucosa pancreatojejunostomy was performed on all patients. The ISGPF criteria were used to define postoperative pancreatic fistula.Results: Conventional pancreatoduodenectomy was performed in 84 patients and pylorus-preserving pancreatoduodenectomy in 163. Postoperative complications occurred in 144 (58.3%) patients, but there was no postoperative in-hospital mortality. Pancreatic fistula occurred in 105 (42.5%) [grade A, 82 (33.2%); grade B, 9 (3.6%); grade C, 14 (5.7%)]. However, no difference was evident between the no fistula group and the grade A fistula group in terms of clinical findings, including postoperative hospital stays (11 versus 12 days, respectively, p = 0.332). Mean durations of hospital stay in the grade B and C fistula groups were significantly longer than in the no fistula group (21 and 28.5 days, respectively; p < 0.001). Multivariate analysis revealed that a soft pancreas and a long operation time (>300 min) were individually associated with pancreatic fistula formation of grades B and C.Conclusions: Although the new ISGPF classification appears to be sound in terms of postoperative pancreatic leakage, grade A fistulas lack clinical implications; thus, we are of the opinion that only grade B and C fistulas should be considered in practice. A soft pancreatic texture and an operation time exceeding 300 min were found to be risk factors of grade B and C pancreatic fistulas. [ABSTRACT FROM AUTHOR]

Background: High-quality bowel preparation is necessary for colonoscopy. A few studies have been conducted to investigate improvement in bowel preparation quality through patient education. However, the effect of patient education on bowel preparation has not been well studied.Methods: A randomized and prospective study was conducted. All patients received regular instruction for bowel preparation during a pre-colonoscopy visit. Those scheduled for colonoscopy were randomly assigned to view an educational video instruction (video group) on the day before the colonoscopy, or to a non-video (control) group. Qualities of bowel preparation using the Ottawa Bowel Preparation Quality scale (Ottawa score) were compared between the video and non-video groups. In addition, factors associated with poor bowel preparation were investigated.Result: A total of 502 patients were randomized, 250 to the video group and 252 to the non-video group. The video group exhibited better bowel preparation (mean Ottawa total score: 3.03 ± 1.9) than the non-video group (4.21 ± 1.9; P < 0.001) and had good bowel preparation for colonoscopy (total Ottawa score <6: 91.6 % vs. 78.5 %; P < 0.001). Multivariate analysis revealed that males (odds ratio [OR] = 1.95, P = 0.029), diabetes mellitus patients (OR = 2.79, P = 0.021), and non-use of visual aids (OR = 3.09, P < 0.001) were associated with poor bowel preparation. In the comparison of the colonoscopic outcomes between groups, the polyp detection rate was not significantly different between video group and non-video group (48/250, 19.2 % vs. 48/252, 19.0 %; P = 0.963), but insertion time was significantly short in video group (5.5 ± 3.2 min) than non-video group (6.1 ± 3.7 min; P = 0.043).Conclusion: The addition of an educational video could improve the quality of bowel preparation in comparison with standard preparation method.Trial Registration: Clinical Research Information Service KCT0001836 . The date of registration: March, 08(th), 2016, Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to develop an assessment tool for activities of daily living (ADL) from the perspective of patients with Parkinson's disease (PD) and examine the validity and reliability of the assessment.Methods: A preliminary 45-item questionnaire was developed through intensive interviews with 54 patients with PD and administered to another group of 248 patients with PD. Based on clinical and statistical analyses, 20 ADL-items were selected. The final 20-item questionnaire was examined in the other group of 59 patients with PD.Results: The new ADL questionnaire showed high internal consistency (Cronbach's α, 0.962-0.966) and acceptable test-retest reliability (0.632-0.984). Concurrent validity was shown as a significant positive correlation between the new ADL questionnaire and other ADL or clinical instruments. The Hoehn and Yahr stage showed the highest degree of correlation with the new ADL questionnaire, followed by the other ADL scales (Schwab and England ADL and the ADL subscore of the Unified Parkinson's Disease Rating Scale). Additionally, a regression analysis was conducted with the disease-specific quality of life questionnaire, and the new ADL questionnaire was the most powerful predictor of quality of life among the clinical instruments.Conclusions: The new ADL questionnaire is a valid tool for assessing ADL from the perspectives of patients with PD. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine the clinical characteristics of women with double primary cancers of the colorectum and endometrium and assess the probability of Lynch syndrome.Study Design: We identified 15 women with paraffin-embedded blocks available who were diagnosed, treated and followed for double primary colorectal and endometrial cancers at in a single institution between 1994 and 2014. If there was a family history that met the revised Amsterdam criteria for Lynch syndrome, the woman was considered to have 'clinically defined Lynch syndrome'. If immunohistochemical (IHC) loss of expression of mismatch repair genes (MLH1, MSH2, MSH6, or PMS2) or high microsatellite instability (MSI) was demonstrated in molecular testing, the case was considered 'suspected Lynch syndrome'.Results: The incidence of clinically defined Lynch syndrome according to the revised Amsterdam criteria was 66% (8 of 15). All 8 of the women clinically diagnosed with Lynch syndrome had either abnormal IHC loss or MSI-high, indicating a suspected Lynch syndrome. Furthermore, 27% (4 of 15) experienced second primary colorectal cancer or other Lynch syndrome-related cancers. Overall, 66% (10 of 15) met the criteria for clinically defined Lynch syndrome or suspected Lynch syndrome.Conclusions: Based on our findings, a large percentage (66%) of women with double primary cancers of the colorectum and endometrium are likely to be diagnosed with Lynch syndrome. [ABSTRACT FROM AUTHOR]

Objectives: To compare outcomes and rates of optimal stent placement between optical coherence tomography (OCT) and intravascular ultrasound (IVUS) guided percutaneous coronary intervention (PCI).Background: Unlike IVUS-guided PCI, rates of clinical outcomes and optimal stent placement have not been well characterized for OCT-guided PCI.Methods: The study enrolled 290 patients who underwent implantation of a second generation drug eluting stent under OCT (122 patients) or IVUS (168 patients) guidance. The two groups were compared after adjusting for baseline differences using 1:1 propensity score matching (PSM) (114 patients in each group). Optimal stent placement was defined as achieving an adequate lumen (optimal minimum stent area [MSA > 4.85 mm(2) for OCT, >5 mm(2) for IVUS] or a final MSA ≥ 90% of the distal reference lumen area, without edge dissection, incomplete stent apposition, or tissue prolapse), or otherwise performing additional interventions to address suboptimal post-stenting OCT or IVUS findings. The primary endpoint was one-year cumulative incidence of major adverse cardiac events (MACE; cardiac death, myocardial infarction and target lesion revascularization). Definite or probable stent thrombosis (ST) rates were evaluated.Results: In adjusted comparisons between OCT and IVUS groups, there was no significant difference in rates of MACE (3.5% vs. 3.5%, P = 1.000) and ST (0% vs. 0.9%, P = 1.000) at 1 year, optimal stent placement (89.5% vs. 92.1%, P = 0.492), and further intervention (7.9% vs.13.2%, P = 0.234), despite OCT significantly more frequently detecting tissue prolapse (97.4% vs. 47.4%, P < 0.001), and numerically more edge dissection (10.5% vs. 4.4%, P = 0.078) or incomplete stent apposition (48.2% vs. 36.8%, P = 0.082).Conclusions: OCT guidance showed comparable results to IVUS in mid-term clinical outcomes, suggesting that OCT can be an alternative tool for stent placement optimization. [ABSTRACT FROM AUTHOR]

Aims: Cisplatin, a platinum-based drug, is an important weapon against many types of cancer. It is well-known that cisplatin induces apoptosis. Potassium channel plays very important role in several signaling pathways. To investigate the possibility that potassium channels also have a role in the cellular response to cisplatin, we examined the effect of cisplatin on the activity of potassium channels on CT26 cell, the colon carcinoma cell line.Materials and Methods: The cells were cultured in DMEM, supplemented with 10< heat-inactivated fetal bovine serum. At mid-log phase, cultures were harvested, washed twice in phosphate-buffered saline, and resuspended in culture medium before use. Cells were voltage-clamped using the whole-cell patch clamp technique. Membrane current data were collected and amplified.Statistical Analysis: Differences between two groups were assessed by paired t-test and one sample t-test to compare the relative values. One-way ANOVA was used for all experiment with more than two groups.Results: Potassium currents were detected in CT26 cells and the currents were reduced by the application of tetraethylammonium (TEA) chloride, iberiotoxin, a big conductance calcium-activated potassium channel blocker and barium. The potassium currents were enhanced to 192< by the application of cisplatin (0.5 mM). Moreover, the increase of potassium currents by cisplatin was further inhibited by the application of TEA confirming the action of cisplatin on potassium channels. In addition, relative current induced by cisplatin in CT26 cells was bit larger than in normal IEC-6 cells.Conclusion: Potassium currents were detected in CT26 cells and the currents were reduced by the application of tetraethylammonium (TEA) chloride, iberiotoxin, a big conductance calcium-activated potassium channel blocker and barium. The potassium currents were enhanced to 192< by the application of cisplatin (0.5 mM). Moreover, the increase of potassium currents by cisplatin was further inhibited by the application of TEA confirming the action of cisplatin on potassium channels. In addition, relative current induced by cisplatin in CT26 cells was bit larger than in normal IEC-6 cells. [ABSTRACT FROM AUTHOR]

Background: Published studies on laparoscopic surgery for transverse colon cancer are scarce. More studies are necessary to evaluate the feasibility, safety, and long-term oncologic outcomes of laparoscopic surgery for transverse colon cancer.Subjects and Methods: From April 1996 to December 2010, 102 consecutive patients with stage II or III disease who had undergone curative resection for transverse colon cancer were enrolled. Seventy-nine patients underwent laparoscopy-assisted colectomy (LAC), whereas 23 patients underwent conventional open colectomy (OC). Short- and long-term outcomes of the two groups were compared.Results: The OC group had a larger tumor size (7.6 ± 3.4 cm versus 5.2 ± 2.3 cm, P = .004) and more retrieved lymph nodes (26.4 ± 11.6 versus 17.5 ± 9.4, P = .002), without differences in resection margins. In the LAC group, return to diet was faster (4.5 ± 1.2 days versus 5.4 ± 1.8 days, P = .013), and postoperative hospital stay was shorter (12.1 ± 4.2 days versus 15.9 ± 4.8 days, P = .000). There were no differences in occurrence of intra- or postoperative complications. There were no statistically significant differences in overall survival rate (OS) or disease-free survival rate (DFS) between the two groups (5-year OS, 90.4% versus 90.5%, P = .670; 5-year DFS, 84.2% versus 90.7%, P = .463).Conclusions: Laparoscopic surgery for transverse colon cancer has better short-term outcomes compared with open surgery, with acceptable long-term outcomes. As in colorectal cancer of other sites, laparoscopic surgery can be a feasible alternative to conventional surgery for transverse colon cancer. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether the benefits of post-resuscitative percutaneous coronary intervention (PCI) are equally observed across out-of-hospital cardiac arrests (OHCAs) with different clinical presentations. The purpose of this study was to assess the effect of PCI in outcomes of OHCA and to compare patient prognosis by history of heart disease (HD) and presentations of nonshockable vs. shockable arrest rhythm by electrocardiogram (ECG).Methods: A population-based observational study was conducted on OHCAs of cardiac etiology in Korea who survived to admission between 2009 and 2013. Multivariable logistic regression analyses were conducted to assess the associations between PCI and outcomes (favorable neurological outcome and survival-to-discharge) and to test the interaction effects of PCI with history of HD and with presence of shockable rhythm.Results: A total of 9762 OHCAs were analyzed. PCI was done in 1140 (11.7%), and neurological recovery were observed in 45.7% of the PCI group and 13.3% of the untreated group. Effects of PCI on neurological recovery were observed similarly in patients with and without history of HD (OR=2.33 (1.62-3.35) and OR=2.37 (1.95-2.89), respectively). PCI was associated with survival-to-discharge only in patients without history of HD (OR=1.80 (1.51-2.15)). PCI was associated with neurological recovery and survival-to-discharge in both shockable and nonshockable rhythms, although the estimates were relatively higher in those with nonshockable rhythms (OR for neurological recovery=2.60 (2.04-3.32); and OR for survival=1.78 (1.46-2.17)).Conclusions: This study corroborates that PCI is an advantageous treatment option for all patients with OHCA regardless of established diagnosis with HD and presentations of shockable rhythm. [ABSTRACT FROM AUTHOR]

Background: Volume-controlled ventilation with a prolonged inspiratory to expiratory ratio (I:E ratio) has been used to optimize gas exchange and respiratory mechanics in various surgical settings. We hypothesized that, when compared with an I:E ratio of 1:2, a prolonged I:E ratio of 1:1 would improve respiratory mechanics without reducing cardiac output (CO) during pneumoperitoneum and steep Trendelenburg positioning, both of which can impair respiratory function in robot-assisted laparoscopic radical prostatectomy. Furthermore, we evaluated its effect on oxygenation during robot-assisted laparoscopic radical prostatectomy.Methods: Eighty patients undergoing robot-assisted laparoscopic radical prostatectomy were randomly allocated to receive an I:E ratio of either 1:1 (group 1:1) or 1:2 (group 1:2). The primary endpoint, peak airway pressure (Ppeak), as well as hemodynamic data, including cardiac output (CO) and arterial oxygen tension (PaO2), were compared between groups at four time points: ten minutes after anesthesia induction (T1), 30 and 60 min after pneumoperitoneum with steep Trendelenburg positioning (T2 and T3), and ten minutes after supine positioning (T4). Overall comparisons were made between groups using linear mixed model analysis with post hoc testing of individual time points adjusted using a Bonferroni correction.Results: Linear mixed model analysis showed a significant overall difference in Ppeak between the two groups (P < 0.001). Post hoc analysis showed a significantly lower mean (SD) Ppeak in group 1:1 than in group 1:2 at T2 [28.4 (4.0) cm H2O vs 32.8 (5.2) cm H2O, respectively; mean difference, 4.3 cm H2O; 95% confidence interval (CI), 2.3 to 6.4; P < 0.001] and T3 [27.8 (3.9) cm H2O vs 32.6 (5.0) cm H2O, respectively; mean difference, 4.7 cm H2O; 95% CI, 2.7 to 6.7; P < 0.001]. The CO assessed over these time points was comparable in both groups (P = 0.784). In addition, there were no significant differences in PaO2 between the two groups (P = 0.521).Conclusions: Compared with an I:E ratio of 1:2, a ratio of 1:1 lowered Ppeak without reducing CO during pneumoperitoneum and steep Trendelenburg positioning. Nevertheless, our results did not support its use solely for improving oxygenation. This trial was registered at http://clinicaltrials.gov/ (NCT01892449). [ABSTRACT FROM AUTHOR]

Background: Several inflammatory response materials could be used for prediction of prognosis of cancer patients. The neutrophil lymphocyte ratio (NLR), and the platelet lymphocyte ratio (PLR) have been introduced for prognostic scoring system in various cancers. The objective of this study was to determine whether the NLR or the PLR would predict the clinical outcomes in advanced gastric cancer patients treated with oxaliplatin/ 5-fluorouracil (FOLFOX).Methods: The study population consisted of 174 advanced gastric cancer patients. Patients were treated with 85 mg/m2 of oxaliplatin as a 2-h infusion at day 1 plus 20 mg/m2 of leucovorin over 10 min, followed by 5-FU bolus 400 mg/m2 and 22-h continuous infusion of 600 mg/m2 at days 1-2. Treatment was repeated in 2-week intervals. The NLR and PLR were calculated from complete blood counts in laboratory test before and after first cycle of chemotherapy.Results: NLR was a useful prognostic biomarker for predicting inferior overall survival (OS) (p = 0.005), but was not associated with progression free survival (PFS) (p = 0.461). The normalization of NLR after one cycle of chemotherapy was found to be in association with significant improvement in PFS (5.3 months vs. 2.4 months, p < 0.001), and OS (11.9 months vs. 4.6 months, p < 0.001). The normalization of PLR was also associated with longer PFS (5.6 months vs. 3.4 months, p = 0.006), and OS (16.9 months vs. 10.9 months, p = 0.002). In multivariate analysis, changes in NLR were associated with PFS (Hazard ratio (HR): 2.297, 95% confidence interval (CI): 1.429-3.693, p = 0.001). The NLR, (HR: 0.245, 95% CI: 0.092-0.633, p = 0.004), PLR (HR: 0.347, 95% CI: 0.142-0.847, p = 0.020), changes in NLR (HR: 2.468, 95% CI: 1.567-3.886, p < 0.001), and changes in PLR (HR: 1.473, 95% CI: 1.038-2.090, p = 0.030) were independent prognostic markers for OS.Conclusion: This study demonstrates that NLR, PLR, and changes in NLR or PLR are independent prognostic factor for OS in patients with advanced gastric cancer treated with chemotherapy. These specific factors may also help in identifying the patients, who are more sensitive to FOLFOX regimen. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the efficacy and safety of S-1 combined with docetaxel (SD) following doxorubicin plus cyclophosphamide (AC) as neoadjuvant therapy in patients with HER2-negative, stage II-III breast cancer.Methods: Patients received AC every 3 weeks for four cycles followed by S-1 (30 mg/m2 orally b.i.d. on days 1-14) and docetaxel (75 mg/m2 i.v. on day 1) every 3 weeks for four cycles. The primary endpoint was the pathological complete response (pCR) rate in breast and axillary lymph nodes.Results: The study included 49 patients with a median age of 43 years. The median breast tumor size was 4.0 cm by palpation. All patients were positive for involvement of axillary lymph node and five patients also had supraclavicular lymph node metastasis, which was confirmed by histological examination. In total, 85.4% of patients (41/49) completed eight cycles of therapy and 95.9% of patients (47/49) received curative surgery. The pCR rate was 22.5% (n = 11). The clinical response rate was 67.4%. During SD chemotherapy, the most frequent grade 3-4 toxicity was neutropenia (8.5% by cycle). There was a single treatment-related mortality from severe neutropenia. Grade 3 S-1 specific toxicities such as epigastric pain (12.2% by person), stomatitis (4.1% by person), and diarrhea (2.0% by person) were also observed. In particular, gastrointestinal discomfort led to dose reduction of S-1 in 45.8% of patients.Conclusions: Given all axillary lymph node positive diseases, neoadjuvant S-1 combined with docetaxel following AC showed a favorable anti-tumor activity but gastrointestinal discomfort should be carefully considered for future studies.Trial Registration: NCT00994968. [ABSTRACT FROM AUTHOR]

Abstract: The objective of this study was to evaluate the positive predictive value (PPV) in ultrasonographically (US)-detected breast lesions of BI-RADS category 4a, 4b and 4c and to find how various clinical factors influenced the PPV of category 4. A total of 2142 women with 2430 breast lesions diagnosed on US as BI-RADS category 4 and underwent biopsy were included. Among them, 452 (18.6%) were pathologically confirmed as malignancy. PPV of each US BI-RADS subcategory was 7.6% (149/1963) for category 4a, 37.8% (68/180) for category 4b and 81.9% (235/287) for category 4c. Several clinical factors were more significantly seen in malignancy of category 4a and 4b, whereas none of the factors showed significance in category 4c. Subcategorization of category 4 is a feasible method in predicting malignancy in which patients’ age, lack of multiplicity and symptoms affected the PPV of category 4 lesions. (E-mail: ekkim@yuhs.ac) [Copyright &y& Elsevier]

According to a previous review, multiple mucosa-associated lymphoid tissue (MALT)-organs involving marginal zone B cell lymphomas (MZLs) are present in 10-30% of patients. However, the clinical features and specific relationships among involved organs are yet to be clearly identified. In this study, we conducted retrospective analyses of multiple MALT organs involving MZLs (MM-MZLs) to identify their clinical features, treatment, prognosis, and specific relationships among involved organs. For analysis, between June 1987 and June 2009, a total of 55 patients from 17 different institutions in Korea, all of whom were histologically diagnosed with MM-MZL, were included in this study. MM-MZL was defined as MZL involving more than 2 different MALT organs. Multiple involvements within one MALT organ (e.g. both side ocular lesions, multiple lung nodules, and multiple stomach lesions, etc.) were excluded from this study. The male/female ratio of the 55 patients was 41/14. The median age of our subjects was 59 years (range 30-82 years). MM-MZL without lymph node (LN) was detected only in 9 patients (36.2%). Bone marrow (BM) involvement was observed in 17 patients (30.9%). The most common site of involvement was the gastrointestinal (GI) tract (25 patients, 45.5%) followed by the lung (40%), Waldeyer's ring (WR) (27.3%), and ocular area (25.5%). Ocular MZLs were commonly accompanied with WR- or lung-MZLs. GI-MZLs were WR or GI-MZLs. Lung-MZLs were frequently observed with ocular and GI-MZLs. WR-MZLs were ocular or GI-MZLs. A total of 53 patients were treated, and 2 on watchful wait. As much as 48 patients received chemotherapy-based treatment. Among them, CR or PR was achieved in 38 patients (79.2%, 95% CI 67-91%). Median time to progression (TTP) was 2.3 years (95% CI 1.4-3.2 years). Cause-specific overall survival (OS) did not reach the median value. The 5-year OS rate was 84.9%. MM-MZLs tend to be an indolent disease, characterized by prolonged survival with frequent relapses. The majority of cases could be controlled effectively via chemotherapy-based treatment, and prolonged survival was achieved in those patients. The GI, lung, WR, and ocular area were commonly presented with other MALT site MZLs, and an organ-specific relationship appears to be relevant to MM-MZLs. [ABSTRACT FROM AUTHOR]

Background: The degree of intratumoral microvascular density is thought to affect tumor metastasis and prognosis in various human cancers, including gastric cancer. Despite recent medical advancements, gastric adenoma or adenocarcinoma remains a considerable therapeutic challenge. Endoscopic submucosal dissection (ESD) is a more recent approach that is now commonly used for radical resection of gastric adenoma and adenocarcinoma.Aim and Methods: The expression of vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), and interleukin-6 (IL-6) are related to the prognosis of gastric adenocarcinoma. However, the expression of these factors in gastric adenoma/adenocarcinoma following ESD has not been clearly evaluated. Here, we report on our study of the expression of VEGF, EGFR, and IL-6 by immunohistochemical staining in extracted tissue from adenoma or adenocarcinoma of the stomach by ESD and subsequent evaluation of the correlation of VEGF, EGFR, and IL-6 with other clinicopathological parameters. The patient cohort consisted of 102 patients with adenoma or adenocarcinoma of the stomach.Results: Immunohistochemical staining for VEGF and IL-6 was significantly higher in both high grade dysplasia and adenocarcinoma than in low grade dysplasia (P < 0.05). There was significant correlation between histological grade and intensity of immunohistochemical staining of VEGF (P = 0.039). Histological differentiation of adenocarcinoma was related to IL-6 expression (P = 0.028). The immunoreactivity of VEGF and IL-6 increased significantly in lesions >2 cm compared to lesions <2 cm (P < 0.05).Conclusion: The immunohistochemical expression of IL-6 and VEGF can be considered to be useful for clinical diagnosis and follow-up of adenoma or adenocarcinoma of the stomach. [ABSTRACT FROM AUTHOR]

Both mitochondrial dysfunction and alterations in mitochondrial DNA (mtDNA) are implicated in type 2 diabetes mellitus and insulin resistance. Evidence also suggests that metabolism of S-adenosyl-L-methionine (SAM), the universal methyl donor for biological methylation, is associated with mitochondrial dysfunction and insulin resistance. We investigated the effect of SAM on mtDNA density and insulin sensitivity using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, an animal model of type 2 diabetes mellitus and insulin resistance. To determine the short-term effect on mtDNA density, SAM (15 mg.kg-1.d-1) was administered intraperitoneally for 7 d to 6 male, 57-wk-old OLETF rats and 6 Long-Evans Tokushima Otsuka (LETO) rats of the same age as a nondiabetic control. To determine the long-term effect, the same dose of SAM was administered daily to 5 male, 6-wk-old OLETF rats until the age of 25 wk; 7 control OLETF rats received vehicle and 7 LETO rats were untreated. Skeletal muscle mtDNA density was measured by either competitive or multiplex PCR and insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. SAM treatment for 1 wk increased skeletal muscle mtDNA density of both OLETF and LETO rats. The long-term SAM treatment significantly reduced body weight gain as well as increased skeletal muscle mtDNA density and whole body insulin sensitivity in OLETF rats compared with their vehicle-treated controls. Furthermore, in all 3 groups, skeletal muscle mtDNA density correlated with insulin sensitivity (r=0.752, P<0.001). In conclusion, SAM treatment increased mtDNA density in the skeletal muscle, improved whole body insulin sensitivity, and prevented body weight gain in OLETF rats. [ABSTRACT FROM AUTHOR]

Gastric adenocarcinoma is the second leading cause of cancer death worldwide. In Western series, survival rates vary widely and are generally lower than those reported from Eastern series. We performed a retrospective analysis of cases operated on at the Johns Hopkins Hospital over the past 18 years and collected data on demographics, tumor characteristics, pathologic stage, treatment methods, complications, survival time, and other relevant factors. Survival according to stage of disease, Lauren tumor type, tumor location, time period, and administration of adjuvant therapy was analyzed, and results were compared with those of other Western series. During this period, 436 patients with gastric adenocarcinoma underwent resection. We have shown a statistically significant association between survival and margin status, stage of disease, and Lauren tumor type. Overall 5-year survival was 26%, and 5-year survival after R0 resection was 33%. No significant difference was detected between survival and tumor location, time period of treatment, or administration of adjuvant therapy. Analysis of various Western series reveals major differences between the cohorts under study, such as stage of disease, extent of resection, tumor type, and tumor location. Many of the reported differences among Western series may be due to cohort differences, such as stage of disease, extent of resection, tumor type, and tumor location. [Copyright &y& Elsevier]

AMP-activated protein kinase (AMPK) acts as a cellular energy sensor, being activated during states of low energy charge. Hypothalamic AMPK activity is altered by hormonal and metabolic signals and mediates the feeding response. To determine the effect of diabetes on hypothalamic AMPK activity, we assayed this activity in streptozotocin (STZ)-induced diabetic rats. Compared with control rats, STZ-induced diabetic rats had significant hyperphagia and weight loss. Hypothalamic AMPK phosphorylation and alpha2-AMPK activity were higher and acetyl-CoA carboxylase activity was lower in diabetic rats than in control rats. Chronic insulin treatment or suppression of hypothalamic AMPK activity completely prevented diabetes-induced changes in food intake as well as in hypothalamic AMPK activity and mRNA expression of neuropeptide Y and proopiomelanocortin. Plasma leptin and insulin levels were profoundly decreased in diabetic rats. Intracerebroventricular administration of leptin and insulin reduced hyperphagia and the enhanced hypothalamic AMPK activity in diabetic rats. These data suggest that leptin and insulin deficiencies in diabetes lead to increased hypothalamic AMPK activity, which contributes to the development of diabetic hyperphagia. [ABSTRACT FROM AUTHOR]