Platelet-to-White Blood Cell Ratio Is Associated with Adverse Outcomes in Cirrhotic Patients with Acute Deterioration.

Background: The platelet-to-white blood cell ratio (PWR) is a hematologic marker of the systemic inflammatory response. Recently, the PWR was revealed to have a role as an independent prognostic factor for mortality in patients with hepatitis B virus (HBV)-related acute-on-chronic failure (ACLF) and HBV-related liver cirrhosis (LC) with acute decompensation (AD). However, the prognostic role of the PWR still needs to be investigated in LC patients with AD. In this study, we analyzed whether the PWR could stratify the risk of adverse outcomes (death or liver transplantation (LT)) in these patients. Methods: A prospective cohort of 1670 patients with AD of liver cirrhosis ((age: 55.2 ± 7.8, male = 1226 (73.4%)) was enrolled and evaluated for 28-day and overall adverse outcomes. Results: During a median follow-up of 8.0 months (range, 1.9−15.5 months), 424 (25.4%) patients had adverse outcomes (death = 377, LT = 47). The most common etiology of LC was alcohol use (69.7%). The adverse outcome rate was higher for patients with a PWR ≤ 12.1 than for those with a PWR > 12.1. A lower PWR level was a prognostic factor for 28-day adverse outcomes (PWR: hazard ratio 1.707, p = 0.034) when adjusted for the etiology of cirrhosis, infection, ACLF, and the MELD score. In the subgroup analysis, the PWR level stratified the risk of 28-day adverse outcomes regardless of the presence of ACLF or the main form of AD but not for those with bacterial infection. Conclusions: A lower PWR level was associated with 28-day adverse outcomes, indicating that the PWR level can be a useful and simple tool for stratifying the risk of 28-day adverse outcomes in LC patients with AD.

Yeast-based assays for characterization of the functional effects of single nucleotide polymorphisms in human DNA repair genes.

DNA repair mechanisms maintain genomic integrity upon exposure to various types of DNA damage, which cause either single- or double-strand breaks in the DNA. Here, we propose a strategy for the functional study of single nucleotide polymorphisms (SNPs) in the human DNA repair genes XPD/ERCC2, RAD18, and KU70/XRCC6 and the checkpoint activation gene ATR that are essentially involved in the cell cycle and DNA damage repair. We analyzed the mutational effects of the DNA repair genes under DNA-damaging conditions, including ultraviolet irradiation and treatment with genotoxic reagents, using a Saccharomyces cerevisiae system to overcome the limitations of the human cell-based assay. We identified causal variants from selected SNPs in the present analyses. (i) R594C SNP in RAD3 (human XPD/ERCC2) caused severe reductions in the growth rate of mutant cells upon short-wavelength UV irradiation or chemical reagent treatment. (ii) The growth rates of the selected variants in RAD18, YKU70, and MEC1 were similar to those of wild-type cells on methyl methanesulfonate and hydroxyurea treated media. (iii) We also assessed the structural impact of the SNPs by analyzing differences in the structural conformation and calculating the root mean square deviation, which is a measure of the discordance of the Cα atoms between protein structures. Based on the above results, we propose that these analytical approaches serve as efficient methods for the identification of causal variants of human disease-causing genes and elucidation of yeast-cell based molecular mechanisms.

The association between a positive lactulose methane breath test and rectocele in constipated patients.

OBJECTIVES: Rectocele with constipation might be related to methane (CH4) producing intestinal bacteria. We investigated the breath CH4 levels and the clinical characteristics of colorectal motility in constipated patients with rectocele. METHODS: A database of consecutive female outpatients was reviewed for the evaluation of constipation according to the Rome III criteria. The patients underwent the lactulose CH4 breath test (LMBT), colon marker study, anorectal manometry, defecography and bowel symptom questionnaire. The profiles of the lactulose breath test (LBT) in 33 patients with rectocele (with size ≥ 2 cm) and 26 patients with functional constipation (FC) were compared with the breath test results of 30 healthy control subjects. RESULTS: The mean size of rectocele was 3.52 ± 1.06 cm. The rate of a positive LMBT (LMBT+) was significantly higher in patients with rectocele (33.3%) than in those with FC (23.1%) or healthy controls (6.7%) (p = 0.04). Breath CH4 concentration was positively correlated with rectosigmoid colon transit time in rectocele patients (γ = 0.481, p < 0.01). A maximum high pressure zone pressure > 155 mmHg was a significant independent factor of LMBT+ in rectocele patients (OR = 8.93, 95% CI = 1.14-71.4, p = 0.04). CONCLUSIONS: LMBT+ might be expected in constipated patients with rectocele. Moreover, increased rectosigmoid colonic transit or high anorectal pressure might be associated with CH4 breath levels. Breath CH4 could be an important therapeutic target for managing constipated patients with rectocele.

Positive Glucose Breath Tests in Patients with Hysterectomy, Gastrectomy, and Cholecystectomy.

BACKGROUND/AIMS: This study aimed to investigate the prevalence and characteristics of small intestinal bacterial overgrowth (SIBO) in patients undergoing abdominal surgeries, such as gastrectomy, cholecystectomy, and hysterectomy. METHODS: One hundred seventy-one patients with surgery (50 hysterectomy, 14 gastrectomy, and 107 cholecystectomy), 665 patients with functional gastrointestinal disease (FGID) and 30 healthy controls undergoing a hydrogen (H2)-methane (CH4) glucose breath test (GBT) were reviewed. RESULTS: GBT positivity (+) was significantly different among the surgical patients (43.9%), FGID patients (31.9%), and controls (13.3%) (p<0.01). With respect to the patients, 65 (38.0%), four (2.3%), and six (3.5%) surgical patients and 150 (22.6%), 30 (4.5%), and 32 (4.8%) FGID patients were in the GBT (H2)+, (CH4)+ and (mixed)+ groups, respectively (p<0.01). The gastrectomy group had a significantly increased preference in GBT+ (71.4% vs 42.0% or 41.1%, respectively) and GBT (H2)+ (64.3% vs 32.0% or 37.4%, respectively) compared with the hysterectomy or cholecystectomy groups (p<0.01). During GBT, the total H2 was significantly increased in the gastrectomy group compared with the other groups. CONCLUSIONS: SIBO producing H2 is common in abdominal surgical patients. Different features for GBT+ may be a result of the types of abdominal surgery.

Correlation of knee proprioception with muscle strength and spasticity in stroke patients.

[Purpose] The purpose of this study was to investigate the relationship of knee proprioception with muscle strength and spasticity in stroke patients. [Subjects and Methods] The subjects were 31 stroke patients. The subjects received an explanation of the procedures and methods and provided informed consent before the experiment. A measurement board was used to determine the the proprioception deficit of the knee as a proprioception test. The proprioception test consisted of a passive and active angle reproduction test. A manual muscle test and modified Ashworth scale were used to evaluate knee muscle strength and spasticity level. The data were analyzed using an independent t-test and Spearman correlation. [Results] The results of this study revealed a significant difference between the affected side and non-affected side in the passive angle reproduction test and a significant difference in the correlation of the proprioception level with muscle strength and spasticity level. [Conclusion] This study indicates that the knee proprioception level is associated with spasticity and muscle strength in stroke patients.

Small Intestinal Bacterial Overgrowth Diagnosed by Glucose Hydrogen Breath Test in Post-cholecystectomy Patients.

BACKGROUND/AIMS: Patients undergoing cholecystectomy may have small intestinal bacterial overgrowth (SIBO). We investigated the prevalence and characteristics of SIBO in patients with intestinal symptoms following cholecystectomy. METHODS: Sixty-two patients following cholecystectomy, 145 with functional gastrointestinal diseases (FGIDs), and 30 healthy controls undergoing hydrogen (H2)-methane (CH4) glucose breath test (GBT) were included in the study. Before performing GBT, all patients were interrogated using bowel symptom questionnaire. The positivity to GBT indicating the presence of SIBO, gas types and bowel symptoms were surveyed. RESULTS: Post-cholecystectomy patients more often had SIBO as evidenced by a positive (+) GBT than those with FGID and controls (29/62, 46.8% vs 38/145, 26.2% vs 4/30, 13.3%, respectively; P = 0.010). In the gas types, the GBT (H2) + post-cholecystectomy patients was significantly higher than those in FGIDs patients (P = 0.017). Especially, positivity to fasting GBT (H2) among the GBT (H2)+ post-cholecystectomy patients was high, as diagnosed by elevated fasting H2 level. The GBT+ group had higher symptom scores of significance or tendency in abdominal discomfort, bloating, chest discomfort, early satiety, nausea, and tenesmus than those of the GBT negative group. The status of cholecystectomy was the only significant independent factor for predicting SIBO. CONCLUSIONS: The SIBO with high levels of baseline H2 might be the important etiologic factor of upper GI symptoms for post-cholecystectomy patients.

Breath hydrogen and methane are associated with intestinal symptoms in patients with chronic pancreatitis.

BACKGROUNDS: The bacterial overgrowth might be associated with chronic pancreatitis. This study was to evaluate the prevalence and characteristics of small intestinal bacterial overgrowth (SIBO) in patients with chronic pancreatitis. METHODS: 36 patients with chronic pancreatitis and 49 healthy controls undergoing the hydrogen (H2)-methane (CH4) lactulose breath test (LBT) were reviewed. The LBT positivity (+) indicating the presence of SIBO, gas types, bowel symptom questionnaire, laboratory and radiologic results were surveyed. The LBT+ was (1) an increase in the breath H2 (≥20 ppm) or CH4 (≥10 ppm) over the baseline or (2) a baseline H2 (≥20 ppm) or CH4 (≥10 ppm) within 90 min after lactulose load. RESULTS: LBT+ was significantly higher in the patients (17/36) than in controls (13/49) (47.2% vs. 26.5%, P < 0.05). During LBT, the H2 levels between 0 and 105 min were significantly higher in patients than in controls. Among LBT+ patients, 11 (64.7%), 1 (5.9%), 5 (29.4%) were in the LBT (H2)+, (CH4)+, (mixed)+ groups, respectively. The LBT+ group had significantly higher scores of flatus than those of the LBT- group. Considering the subtypes of LBT, the LBT (mixed)+ group had higher symptom scores of significance or tendency in hard stool, strain, urgency, and flatus than LBT- group The laboratory and radiologic features were not significantly different between LBT+ and LBT- groups. CONCLUSIONS: SIBO is common in patients in chronic pancreatitis. Especially, excretions of mixed H2 and CH4 appear to be related with deterioration of intestinal symptoms.

Changes in proprioception and pain in patients with neck pain after upper thoracic manipulation.

[Purpose] The purpose of this study was to conduct cervical stability training and upper thoracic manipulation for patients with chronic neck pain and then investigate the changes of cervical proprioception and pain. [Subjects and Methods] Subjects were 30 workers with mechanical neck pain, who were randomly divided into an upper thoracic manipulation group and a cervical stability training group. Upper thoracic manipulation after cervical stability training was conducted for the upper thoracic manipulation group, and only stability training was conducted for the cervical stability training group. The intervention period was six weeks, and consisted of three sessions a week, each of which lasted for 30 minutes. For proprioception measurement, an electro-goniometer was used to measure reposition sense before and after the intervention. The visual analogue scale was used to assess pain. [Results] After the intervention, the error angle was significantly smaller in flexion and right left side-bending, and pain was significantly reduced in the upper thoracic manipulation group. According to the post intervention comparison of the two groups, there were significant differences in the proprioception and pain values. [Conclusion] Conducting both cervical stability training and upper thoracic manipulation for patients with chronic neck pain was more helpful for the improvement of proprioception and pain than cervical stability training alone.

The effects of whole body vibration on static balance, spinal curvature, pain, and disability of patients with low back pain.

[Purpose] The purpose of this study was to investigate the impact of whole body vibration (WBV) on static balance, spinal curvature, pain, and the disability of patients with chronic lower back pain. [Subjects and Methods] The subjects were of 40 patients, who were randomly assigned to WBV and control groups. Twenty-five minutes of lumbar stability training and 5 minutes of WBV were conducted for the WBV group, and 30 minutes of lumbar stability training was conducted for the control group. The training was conducted three times per week for a total of 6 weeks. Static balance, spinal curvature, pain, and disability were measured before and after the intervention. [Results] After the intervention, the WBV group showed a significant differences in static balance, spinal curvature, pain, and disability. The control group presented significant differences in pain, and disability. In the comparison of the two groups, the WBV group showed more significant improvements in the fall index and pain. [Conclusion] WBV can be recommended for the improvement of the balance ability and pain of chronic lower back pain patients.

The effects of chest expansion resistance exercise on chest expansion and maximal respiratory pressure in elderly with inspiratory muscle weakness.

[Purpose] The aim of this study was to examine the effect of chest expansion resistance exercises (CERE) on chest expansion, maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) in elderly people with inspiratory muscle weakness. [Subjects] Thirty elderly people with inspiratory muscle weakness (MIP < 80% of the predicted value) were randomly and equally assigned to a chest expansion resistance exercise (CERE) group, core conditioning exercise (CCE) group, and control group. [Methods] The intervention was applied to the CERE group and CCE group five times per week, 30 minutes each time, for six weeks. A tapeline was used to measure upper and lower chest expansion. MIP and MEP before and after the intervention were measured and compared. [Results] There was significant improvement in upper and lower chest expansion and MIP after the intervention in both the CERE group and the CCE group, whereas the control group did not show any significant difference. MEP did not significantly change in any of the three groups after the intervention. [Conclusion] The CERE group underwent greater changes than the CCE group, which proves that the CERE is more effective for improving elderly people's chest expansion capacity and MIP in elderly people. Therefore, application of the CERE by therapists is recommended if the environment and conditions are appropriate for enhancement of chest expansion capacity and MIP in elderly people.

Breath methane positivity is more common and higher in patients with objectively proven delayed transit constipation.

OBJECTIVES: Methane (CH4)-producing intestinal bacteria might be related to constipation. This study was carried out to evaluate the association between breath CH4, colonic transit, and anorectal pressure in constipated patients. METHODS: A database of consecutive 62 constipated patients fulfilling the Rome III with the lactulose CH4 breath test (LMBT), a colon marker study, and anorectal manometry was studied. The profile of LMBT in patients was compared with 49 healthy controls. The positivity to LMBT (LMBT+) was defined as CH4 of at least 10 ppm in baseline or above baseline within 90 min. There were two types of constipation: normal and delayed transit. RESULTS: There were significant differences in the breath CH4 between patients with delayed transit and (a) normal transit from 0 to 135 min or (b) healthy controls from 0 to 180 min. The LMBT+ was higher in delayed transit patients than in healthy controls (58.8 vs.12.2%) or in normal transit patients (vs. 13.3%), respectively (P<0.01). The delayed transit was the only independent factor for LMBT+ [odds ratio (95% confidence interval), 27.8 (3.32-250.00), P<0.01]. The left and total colonic transit time were significantly increased in LMBT-positive than in LMBT-negative patients. Significant correlations were found between total CH4 and the time of left or total colonic transit. However, no difference was found in the parameters of manometry by LMBT status. CONCLUSION: A positive breath CH4 was associated with delayed colonic transit and left colon, and it could be a new therapeutic target for the management of constipated patients with delayed colonic transit.

Clevudine-induced viral response, associated with continued reduction of HBsAg titer, was durable after the withdrawal of therapy.

BACKGROUND: This study was conducted to evaluate the durability of clevudine-induced viral response after the withdrawal of treatment. METHODS: Patients who showed a complete response [alanine aminotransferase (ALT) normalization and hepatitis B virus (HBV) DNA <4,700 copies/mL for hepatitis B envelope antigen (HBeAg)-negative patients; ALT normalization, HBV DNA <4,700 copies/mL, and HBeAg seroconversion for HBeAg-positive patients] in the previous clevudine phase III trials were followed for an additional 96 weeks without any treatment for hepatitis B. RESULTS: Of the 63 patients in the study cohort, 73% and 35% of the patients had HBV DNA <141,500 and <4,700 copies/mL, respectively, and 75% of the patients had normal ALT at the end of follow-up. HBeAg seroconversion was maintained in 81% of the patients and hepatitis B surface antigen (HBsAg) loss occurred in 3 patients. Continued HBsAg titer decrease (-0.5 log IU/mL) was observed in the sustained viral responders, suggesting the reduction of covalently closed circular DNA in hepatocytes. CONCLUSIONS: The clevudine-induced viral response was durable in the majority of patients for 2 years after the withdrawal of treatment.

An inflammatory myofibroblastic tumor of the ampulla of vater successfully managed with endoscopic papillectomy: report of a case.

Inflammatory myofibroblastic tumors (IMTs) are solid neoplastic mesenchymal proliferations composed of myofibroblastic spindle cells admixed with inflammatory infiltrates. The documented sites in the gastrointestinal tract include the esophagus, small intestine, colon, appendix, rectum, pancreas, spleen, liver, and Meckel's diverticulum. Biliary IMTs are rare, and IMTs arising from the ampulla of Vater have not been reported previously. Herein we report the case of a 65-year-old woman with an extrahepatic biliary obstruction due to IMT of the ampulla of Vater, and a successful therapeutic approach using endoscopic ultrasonography and endoscopic papillectomy.

Randomized, multicenter, phase III trial of heptaplatin 1-hour infusion and 5-fluorouracil combination chemotherapy comparing with cisplatin and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer.

PURPOSE: Heptaplatin (Sunpla) is a cisplatin derivative. A phase IIb trial using heptaplatin resulted in a 34% response rate with mild nephrotoxicity. We conducted a randomized phase III trial of heptaplatin plus 5-FU compared with cisplatin plus 5-FU in patients with advanced gastric cancer. MATERIALS AND METHODS: One hundred seventy-four patients (heptaplatin, n=88; cisplatin, n=86) from 13 centers were enrolled. The eligibility criteria were as follows: patients with pathologically-proven adenocarcinoma, chemonaive patients, or patients who had received only single adjuvant chemotherapy, and who had a measurable or evaluable lesion. On day 1, heptaplatin (400 mg/m(2)) or cisplatin (60 mg/m(2)) was given over 1 hour with 5-FU (1 gm/m(2)) on days 1~5 every 4 weeks. RESULTS: At the time of survival analysis, the median overall survival was 7.3 months in the 5-FU + heptaplatin (FH) arm and 7.9 months in the 5-FU + cisplatin (FP) arm (p=0.24). Of the FH patients, 34.2% (complete response [CR], 1.3%; partial response [PR], 32.9%) experienced a confirmed objective response compared with 35.9% (CR 0%, PR 35.9%) of FP patients (p=0.78). The median-time-to-progression was 2.5 months in the FH arm and 2.3 months in the FP arm. The incidence of neutropenia was higher with FP (28%) than with FH (16%; p=0.06); grade 3~4 nausea and vomiting were more frequent in the FP than in the FH arm (p=0.01 and p=0.05, respectively). The incidence of increased proteinuria and creatininemia was higher with FH than with FP; however, there was no statistical difference. There were no treatment-related deaths. CONCLUSION: Heptaplatin showed similar effects to cisplatin when combined with 5-FU in advanced gastric cancer patients with tolerable toxicities.

Phase I dose escalation study of docetaxel with a fixed dose of S-1 in combination chemotherapy for advanced gastric cancer.

BACKGROUND: The primary objectives of this study were to estimate the maximum-tolerated dose (MTD) of docetaxel in combination with a fixed dose of S-1 and to determine the recommended dose (RD). PATIENTS AND METHODS: Patients with histologically proven gastric carcinoma with metastatic or locally advanced inoperable disease were eligible. Patients received intravenous docetaxel starting at 40 mg/m(2) (dose level 1), and stepwise dose increases to 50, 60, and 70 mg/m(2) were planned for successive patient cohorts (dose levels 2, 3, and 4, respectively) over 1 h on day 1 and oral S-1 administered at a fixed dose of 40 mg/m(2) twice daily on days 1-14, both drugs every 21 days. RESULTS: A total of 13 patients were enrolled into this trial. All three patients at dose level 3 developed dose-limiting toxicities (DLT), and this level was declared to be the MTD. Hence, level 2 (docetaxel 50 mg/m(2)) was declared to be the RD for the next study. As 9 of the 13 enrolled patients responded to treatment, the overall objective response rate was 69.2% (95% CI, 44.1-94.3%). The median time to progression was 8.38 months (range 1.44-8.51) and the overall survival duration was 9.9 months (range 0.62-11.57). The most common grade 3/4 toxicity of docetaxel plus S-1 was neutropenia, which was tolerable and manageable. CONCLUSION: This regimen showed encouraging activity and a manageable safety profile in advanced gastric carcinoma and could be used in further randomized studies.

Simultaneous Colonic Obstruction and Hydroureteronephrosis due to Mesenteric Fibromatosis.

Mesenteric fibromatosis (MF) is a rare benign mesenchymal lesion that can occur throughout the gastrointestinal tract, especially small bowel. Its biological behavior is intermediate between benign fibrous tissue proliferation and malignant fibrosarcoma. In previously reported cases of MF, we could find colonic obstruction or ureter obstruction, but simultaneous involvement of colon and ureter was not able to be seen. We described a patient that presented with colonic obstruction and hydroureteronephrosis due to MF at sigmoid colon which mimicked submucosal tumor such as gastrointestinal tumor. This case resulted in a positive positron emission tomography scan suggesting malignant neoplasm, but beta-catenin positivity on immunohistochemical staining separated MF from gastrointestinal stromal tumor and sclerosing mesenteritis. The clinical course of the patient was improved after surgical resection.

Colonic lymphangiomatosis associated with anemia.

Lymphangioma is an uncommon malformation of lymphatic system. Multiple colonic lymphangioma named as lymphangiomatosis is considered an extremely rare disease. Although lymphangioma is a benign tumor and most colonic lymphangiomas do not cause symptoms and do not require treatment, resection of lymphangioma is necessary in the presence of symptoms such as abdominal pain, bleeding, intussusceptions. We report a case of colonic lymphangiomatosis in a man who presented with abdominal discomfort and anemia, which was diagnosed and treated with endoscopic snare polypectomy.

Ischemic colitis associated with intestinal vasculitis: histological proof in systemic lupus erythematosus.

Ischemic colitis is an uncommon complication in patients with systemic lupus erythematosus (SLE). In previously reported cases of colitis caused by SLE, intestinal vasculitis is implicated as the causative process, but is rarely confirmed histologically. We described a case of a 32-year-old man with increased activity of SLE, who presented with hematochezia and abdominal pain due to ischemic colitis with small vessel vasculitis which was proven by sigmoidoscopic biopsy. The clinical course of the patient was improved after steroid and conservative management.