Impact of sunitinib treatment on blood glucose levels in patients with metastatic renal cell carcinoma.

OBJECTIVE: To investigate the effects of sunitinib treatment on blood glucose levels in patients with metastatic renal cell carcinoma. METHODS: We reviewed the records of 48 patients who received sunitinib treatment for metastatic renal cell carcinoma between April 2007 and December 2010 at our institution. Patients' data including diabetic status, diabetes mellitus medication and mean blood glucose levels before, during and after the treatment with sunitinib were assessed. RESULTS: In 10 of the 48 (20.8%) patients who were diabetic, the blood glucose level was observed to be significantly decreased after 4 weeks of sunitinib treatment with the mean decrease in blood glucose level being 76.1 ± 29.0 mg/dl (P = 0.002). Subsequently, after a 2-week off-treatment period, the mean blood glucose level rebound and increased (21.9 ± 6.3 mg/dl, P = 0.038) in these 10 patients. With sunitinib treatment, one patient was able to discontinue diabetes mellitus medication completely during a 4-week treatment period, and three other patients had dosages of their oral diabetes mellitus medication reduced. Among 38 non-diabetic patients, no significant changes in blood glucose levels were observed during both the 4-week sunitinib treatment period and the 2-week off-treatment period. No severe hypoglycemic episode was observed among our subjects. CONCLUSIONS: Sunitinib treatment in diabetic patients with metastatic renal cell carcinoma may result in significantly decreased blood glucose levels. Thus, blood glucose levels should be checked more vigilantly in diabetic patients undergoing sunitinib treatment to adjust diabetes mellitus medications as needed. Further investigation via a larger scaled, prospective study would be needed.

Epidemiological link between gastric disease and polymorphisms in VacA and CagA.

Gastritis, peptic ulcer disease, and gastric cancer are a few of the diverse disease manifestations that have been shown to be associated with infection by Helicobacter pylori. Why some individuals develop more severe forms of disease remains largely unknown. In this study, 225 South Korean strains were genotyped for vacA and then analyzed to determine if particular genotypes varied across disease state, sex, or cagA allele. Of these strains, 206 strains carried an s1/i1/m1 allele, 11 strains carried an s1/i1/m2 allele, and 8 strains carried an s1/i2/m2 allele. By using Fisher's exact test, a statistical association between variations in the cagA and vacA alleles was identified (P = 0.0007), and by using log linear modeling, this variation was shown to affect the severity of disease outcome (P = 0.027). Additionally, we present evidence that variation within the middle region of VacA contributes significantly to the distribution of vacA alleles across gender (P = 0.008) as well as the association with disease outcome (P = 0.011). In this South Korean population, the majority of H. pylori strains carry the vacA s1/i1/m1 allele and the CagA EPIYA-ABD allele. These facts may contribute to the high incidence of gastric maladies, including gastric cancer.

Polymorphism in the CagA EPIYA motif impacts development of gastric cancer.

Helicobacter pylori causes diseases ranging from gastritis to peptic ulcer disease to gastric cancer. Geographically, areas with high incidences of H. pylori infection often overlap with areas with high incidences of gastric cancer, which remains one of the leading causes of cancer-related deaths worldwide. Strains of H. pylori that carry the virulence factor cytotoxin-associated gene A (cagA) are much more likely to be associated with the development of gastric cancer. Moreover, particular C-terminal polymorphisms in CagA vary by geography and have been suggested to influence disease development. We conducted a large-scale molecular epidemiologic analysis of South Korean strains and herein report a statistical link between the East Asian CagA EPIYA-ABD genotype and the development of gastric cancer. Characterization of a subset of the Korean isolates showed that all strains from cancer patients expressed and delivered phosphorylatable CagA to host cells, whereas the presence of the cagA gene did not strictly correlate to expression and delivery of CagA in all noncancer strains.

Impact of timely antibiotic administration on outcomes in patients with severe sepsis and septic shock in the emergency department.

OBJECTIVE: We aimed to investigate the effect of timely antibiotic administration on outcomes in patients with severe sepsis and septic shock. METHODS: We analyzed data from a sepsis registry that included adult patients who initially presented to the emergency department (ED) and met criteria for severe sepsis or septic shock. Timely antibiotic use was defined as administration of a broad-spectrum antibiotic within three hours from the time of ED arrival. Multivariable logistic and linear regression analyses were performed to assess associations between timely administration of antibiotics and outcomes, including hospital mortality, 48-hour change in Sequential Organ Failure Assessment (SOFA) score (delta SOFA), and hospital length of stay (LOS). RESULTS: A total of 591 patients were included in the study. In-hospital mortality was 16.9% for patients receiving timely antibiotics (n=377) and 22.9% for patients receiving delayed antibiotics (n=214; P=0.04). The adjusted odds ratio for in-hospital survival was 0.54 (95% confidence interval [CI], 0.34 to 0.87; P=0.01) in patients who received timely antibiotics. Timely antibiotic administration was also significantly associated with higher delta SOFA (2 vs. 1) and shorter hospital LOS among survivors (11 days vs. 15 days). Multivariable linear regression analyses showed that timely antibiotic administration was significantly associated with increased delta SOFA and decreased hospital LOS. CONCLUSION: Antibiotic administration within three hours from the time of ED arrival was significantly associated with improved outcomes, including in-hospital survival, reversal of organ failure, and shorter hospital LOS, in patients with severe sepsis and septic shock.

Effect of testosterone replacement therapy on bone mineral density in patients with Klinefelter syndrome.

PURPOSE: Klinefelter syndrome (KS) is related to testicular insufficiency, which causes low testosterone levels in serum. Generally, sex hormone levels and bone mineral density (BMD) are lower in patients with KS than normal. We investigated the effects of testosterone replacement on serum testosterone levels and BMD in KS patients. MATERIALS AND METHODS: From December 2005 to March 2008, 18 KS patients with a 47, XXY karyotype were treated with initial intramuscular injections of long-acting testosterone undecanoate (Nebido®, 1000 mg/4 mL) at baseline and second injections after six weeks. An additional four injections were administered at intervals of 12 weeks after the second injection. BMD was measured at the lumbar spine (L2-4), the left femoral neck and Ward's triangle, using dual energy X-ray absorptiometry. Medical histories, physical examinations and prostate specific antigen, hematology and serum chemistry were conducted for each patient. In addition, total testosterone and sex hormone-binding globulin levels were measured. RESULTS: Following testosterone replacement, mean serum total testosterone increased significantly from baseline (0.90 vs. 4.51 ng/mL, p<0.001), and total testosterone rose to normal levels after replacement in all patients. The mean BMD of the lumbar spine increased significantly (0.91 vs. 0.97 g/cm², p<0.001). Similar increases of BMD were also observed at the femoral neck, but this increase was not significant. CONCLUSION: These findings suggest that testosterone replacement therapy may be effective in treating BMD deficiency in men with testosterone deficiency, especially those with Klinefelter syndrome.

One-Year Surgical Outcomes and Quality of Life after Minimally Invasive Sling Procedures for the Treatment of Female Stress Urinary Incontinence: TVT SECUR(R) vs. CureMesh(R).

PURPOSE: We compared the efficacy and safety of two minimally invasive sling procedures used to treat female stress urinary incontinence (SUI), tension-free vaginal tape (TVT) SECUR(R) and CureMesh(R), and assessed the 1-year surgical outcomes. MATERIALS AND METHODS: Sixty women with SUI were assigned to undergo either the TVT SECUR (n=38) or CureMesh (n=22) procedures between April 2007 and June 2008. Patients were monitored via outpatient visits at 1 month, 3 months, and 1 year after surgery. The efficacy of these procedures was evaluated by the cough test or by a urodynamic study. At these postoperative visits, the patients also completed several questionnaires, including incontinence quality of life, patient's perception of urgency severity, the scored form of the Bristol Female Lower Urinary Tract Symptoms, visual analog scale, and questions about perceived benefit, satisfaction, and willingness to undergo the same operation again. The objective cure rate was defined as no leakage during the cough test with a full bladder. The subjective cure rate was evaluated by self-assessment of goal achievement performed 1 year postoperatively. RESULTS: The two groups were similar in preoperative characteristics and urodynamic parameters. The objective cure rates were similar between TVT SECUR and CureMesh (68.4% vs. 77.3%). All respondents reported improvement after surgery. There were no intra-operative complications. CONCLUSIONS: Our results showed that the TVT SECUR and CureMesh procedures are both safe and simple to perform and have no significant differences in efficacy. Comparative studies with long-term follow-up are warranted to determine the true efficacy of these procedures.

Genetic analysis of Helicobacter pylori clinical isolates suggests resistance to metronidazole can occur without the loss of functional rdxA.

Resistance to metronidazole (MTZ) in Helicobacter pylori is associated with mutations in rdxA, encoding an oxygen-insensitive NADPH nitroreductase, and mutations in frxA, encoding a NAD(P)H-flavin oxidoreductase. Despite this association, the strict correlation of MTZ resistance with mutations in rdxA or frxA is still controversial. In this study, rdxA allelic replacement was used to distinguish resistance-associated nucleotide mutations from the natural genetic diversity of H. pylori. Replacement with truncated rdxA resulted in MTZ resistance, whereas replacement with missense-mutated rdxA from resistant clinical isolates failed to yield MTZ resistance. Thus, although truncation of rdxA confers MTZ resistance in G27 H. pylori, MTZ resistance found in other clinical isolates is not due to the identified amino-acid substitutions. Three of our MTZ-resistant clinical isolates expressed functional rdxA and two of these also encoded full-length frxA. Therefore, MTZ resistance can arise in H. pylori possessing functional rdxA, suggesting that other factors are involved in MTZ resistance.