Prognostic significance of c-kit mutation in localized gastrointestinal stromal tumors.

PURPOSE: Constitutive mutational activation of c-kit has been found to be associated with the pathogenesis of gastrointestinal stromal tumors (GISTs). The prognostic significance of c-kit mutations, however, is still controversial. EXPERIMENTAL DESIGN: We examined 86 patients curatively resected for localized GIST. Genomic DNA was extracted from paraffin-embedded tumor tissues. Exons 9, 11, 13, and 17 of the c-kit gene were amplified by PCR and sequenced. RESULTS: Mutations in exon 11 were detected in 61 tumors, and mutations in exon 9 were observed in three tumors, whereas no mutations were detected in exons 13 or 17. The overall c-kit mutation frequency was 74%. Amino acid alterations in the 61 tumors with exon 11 mutations were deletion in 33 tumors, substitution in 20, both deletion and substitution in 4, insertion in 1, and duplication in 3. Histologically, tumors with c-kit mutations showed higher mitotic counts and higher cellularity. The 5-year relapse-free survival (RFS) in patients having GISTs with c-kit mutations was 21%, compared with 60% in those without c-kit mutations. Significantly higher RFS rates were observed in patients with tumors having mitotic counts < 5 mitoses/50 high power field, spindle-cell histology, tumor size < 5 cm, or gastric GISTs. Multivariate analyses indicated association of poorer RFS with a higher mitotic count > or = 5 of 50 high power fields; odds ratio (OR) = 3.0], presence of c-kit mutations (OR = 5.6), and a larger tumor size (> or = 5 cm; OR = 4.2). CONCLUSIONS: The presence of c-kit mutation, along with high mitotic count and larger tumor size, was an independent factor for poor prognosis in patients with localized GISTs.     

Retrograde perfusion sphincterometry with a flexible cystoscope: method of troubleshooting the AMS 800

We developed the technique of retrograde perfusion sphincterometry to troubleshoot the AMS 800 device. We implanted artificial urinary sphincters in men who were incontinent after prostatectomy and performed intraoperative retrograde perfusion sphincterometry. Retrograde perfusion sphincterometry using a flexible cystoscope is simple and allows early recognition of intraoperative urethral injury and mechanical malfunction.     

Takayasu's arteritis: assessment of disease activity with contrast-enhanced MR imaging

OBJECTIVE: The purpose of this study was to evaluate the role of contrast-enhanced MR imaging in the determination of disease activity in patients with Takayasu's arteritis. SUBJECTS AND METHODS: High-resolution contrast-enhanced T1-weighted spinecho MR imaging using small fields of view (14-20 cm) and thin slices (4-5 mm) was performed in 26 patients with Takayasu's arteritis and 16 healthy subjects. The degree of aortic mural enhancement was assessed by measuring signal intensity and by visually estimating it in comparison with that of the myocardium. RESULTS: Contrast-enhanced MR imaging showed more enhancement of thickened aortic wall compared with myocardium, thus suggesting active Takayasu's arteritis on MR imaging in 16 patients. Determination of disease activity using contrast-enhanced MR imaging was concordant with clinical findings in 23 patients (88.5%). Contrast-enhanced MR findings were concordant with laboratory findings in most patients (erythrocyte sedimentation rate in 92.3% [24/26] and C-reactive protein in 84.6% [22/26]). The measured signal intensity of the aortic wall relative to that of myocardium during the early phase of contrast-enhanced MR imaging correlated well with the erythrocyte sedimentation rate (r = 0.78, p < 0.005) and with the C-reactive protein level (r = 0.63, p < 0.005). CONCLUSION: Contrast-enhanced MR imaging provides information about disease activity of Takayasu's arteritis, which may be useful in the diagnosis and treatment of Takayasu's arteritis.     

Prevention of encephalomyocarditis virus-induced diabetes by live recombinant Mycobacterium bovis bacillus Calmette-Guérin in susceptible mice

The D variant of encephalomyocarditis (EMC-D) virus causes diabetes in susceptible mice by direct cytolysis of pancreatic beta-cells. cDNA covering the major outer capsid protein (VP1) of the EMC-D virus was cloned into Mycobacterium bovis bacillus Calmette-Guerin (BCG). None of the SJL/J mice immunized with live recombinant BCG-VP1 (rBCG-VP1) became diabetic when challenged with the highly diabetogenic EMC-D virus, but the control mice inoculated with normal BCG developed diabetes during the same challenge. VP1-specific antibodies (including neutralizing antibodies) were markedly increased over time and reached the maximum titer at week 10 after a single immunization. The plateau of the titer lasted longer than 4 weeks. Mice and guinea pigs immunized with live rBCG-VP1 showed strong delayed-type hypersensitivity to the VP1 of the EMC-D virus. The preventive immunity still worked effectively 10 months after the primary immunization. At that time, the VP1-specific antibody was almost undetectable in the bloodstream, but a large number of VP1-specific lymphocytes was found in the spleen of the immunized mice. Our results show that live rBCG-VP1 elicits effective humoral and long-lasting cellular immune responses against EMC-D virus infection that results in the prevention of virus-induced diabetes in susceptible mice.     

Antimicrobial mesh versus vaginal wall sling: a comparative outcomes analysis

PURPOSE: We prospectively compared transvaginal antimicrobial mesh (MycroMesh*) and anterior vaginal wall slings using an outcomes analysis. MATERIALS AND METHODS: Between August 1997 and November 1998 we implanted transvaginal slings in 40 consecutive women randomized to a synthetic mesh (20) or vaginal wall (20) group. All patients had documented stress urinary incontinence on preoperative urodynamics. We prospectively compared postoperative outcomes data obtained from pelvic examinations, cough stress test, cotton swab test and validated patient questionnaires using a visual analog scale. RESULTS: Complete followup was available in all patients. Mean followup was 22 months (range 12 to 27). Stress incontinence was cured in 95% of the mesh and 70% of the vaginal wall group, and pelvic prolapse was cured in 100% and 95%, respectively. Transient de novo urge incontinence was noted in 12.5% of the mesh and 14.3% of the vaginal wall group. Mean postoperative cotton swab angle during Valsalva's maneuver was 20 and 45 degrees for the mesh and vaginal wall groups, respectively. The incidence of urinary retention and tissue erosion was 0% for both groups. The satisfaction rate was 100% and 80% for the mesh and vaginal wall groups, respectively. CONCLUSIONS: The antimicrobial MycroMesh sling was superior to the vaginal wall sling for correction of stress incontinence and pelvic prolapse with comparatively low morbidity.     

Isolation and Genetic Characterization of a Bovine Coronavirus KBR-1 Strain from Calf Feces in South Korea

Bovine coronavirus (BCoV) causes severe diarrhea in neonatal calves, winter dysentery in adult cattle, and respiratory disease in feedlot cattle, resulting in economic losses. A total of 16/140 calf diarrheic feces samples collected in South Korea between 2017 and 2018 were positive for BCoV. Phylogenetic analysis of the complete spike and hemagglutinin/esterase genes revealed that the 16 Korean BCoV strains belonged to group GIIa along with Korean strains isolated after 2000, whereas Korean BCoV strains isolated before 2000 belonged to group GI. Mice and goats inoculated with an inactivated KBR-1 strain (isolated from this study) generated higher antibody titers (96 ± 13.49 and 73 ± 13.49, respectively) when mixed with the Montanide01 adjuvant than when mixed with the Carbopol or IMS1313 adjuvants. Viral antigens were detected in the large intestine, jejunum, and ileum of calves inoculated with inactivated KBR-1 vaccine (10^4.0 TCID₅₀/mL) at 14 days of post-challenge (DPC). However, no viral antigens were detected in calves vaccinated with a higher dose of inactivated KBR-1 strain (10^6.0 TCID₅₀/mL) at 14 DPC, and they had high antibody titers and stable diarrhea scores. Currently, the group GIIa is prevalent in cows in South Korea, and although further research is needed in the future, the recently isolated KBR-1 strain has potential value as a new vaccine candidate.     

Which factors are helpful for the early determination of treatment level in patients with interstitial lung disease in the intensive care unit to minimize the suffering in their end of life?: A retrospective study

Interstitial lung disease (ILD) is widely known to be associated with high mortality and poor prognosis, especially in patients admitted to the intensive care unit (ICU). The objective of this study was to investigate clinical predictors for assisting relatively early decision of treatment level in the ICU. We retrospectively investigated patients with ILD who were admitted to the ICU between January 1, 2014, and September 30, 2019. A total of 64 patients were analyzed. We found the ICU and hospital mortality rates to be 67.2% and 69.8%, respectively. Nonsurvivors had a higher fraction of inspired oxygen (FiO₂) on days 1 (79 ± 21 vs 60% ± 21%, P = .001) and 3 (61 ± 31 vs 46% ± 19%, P = .004). They showed lower partial pressure of oxygen/FiO₂ (PF) ratio on days 1 (134 ± 80 vs 173 ± 102, P = .049) and 3 (147 ± 74 vs 235 ± 124, P = .003) than the survivor group. The lactic acid levels obtained on day 1 and PF ratio measured on day 3 were associated with mortality (odds ratio, 1.89; 95% confidence interval 1.03–3.47 and odds ratio, 0.99; 95% confidence interval 0.98–1.00, respectively). Among the 31 ICU survivors, 10 patients died in the general ward, 12 patients died after hospital discharge; only 9 patients survived after 1 year. We suggest that these clinical predictors could be used to determine the level of further treatment or withdrawal on day 3 of admission in patients with ILD admitted to the ICU to minimize the prolonged suffering in a relatively early period.