A multicenter phase II study of everolimus in patients with progressive unresectable adenoid cystic carcinoma

BACKGROUND: The aim of this study was to examine the efficacy and safety of everolimus in patients with progressive unresectable adenoid cystic carcinoma (ACC). METHODS: Histologically confirmed ACC patients with documented disease progression within 12 months prior to the study entry were eligible. Everolimus was given at a dose of 10 mg daily until progression or occurrence of unacceptable toxicities. The primary endpoint was a 4-month progression-free survival (PFS). RESULTS: A total of 34 patients were enrolled. The 4-month PFS probability was 65.5% (95% one-sided confidence interval [CI], 47.7 to infinity). Median PFS duration was 11.2 months (95% CI, 3.6 to 15.8). Complete or partial response was not achieved. Twenty-seven (79.4%, 95% CI, 63.2 to 89.6) patients showed stable disease (SD). Tumor shrinkage within SD criteria was observed in 15 patients (44.1%) and SD lasting 6 months was observed in 13 patients (38.2%). Four patients had disease progression. Among the 18 patients with both pre- and post-treatment (at 8 weeks) FDG-PET scans available, 8 patients (44.4%) showed a partial metabolic response, defined as a ≥25% reduction in maximum standardized uptake values (SUVmax). The most common adverse events were stomatitis, anemia, asthenia, and leukopenia. No unexpected everolimus related toxicities were reported. CONCLUSIONS: Everolimus showed promising efficacy and good tolerability in progressive unresectable ACC. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT0115284

Pneumatosis Intestinalis with Pneumoperitoneum Mimicking Intestinal Perforation in a Patient with Myelodysplastic Syndrome after Hematopoietic Stem Cell Transplantation

Pneumatosis intestinalis (PI) is an uncommon disorder characterized by an accumulation of gas in the bowel wall, and has been associated with a variety of disorders and procedures. We describe a 35-year-old man who undertook hematopoietic stem cell transplantation due to myelodysplastic syndrome. An abdominal X-ray demonstrated extensive PI with pneumoperitoneum mimicking hollow organ perforation. However, the patient had no abdominal symptoms and there was no evidence of peritoneal inflammation. After two weeks of conservative management, including bowel rest and antibiotics, his pneumoperitoneum resolved spontaneously without any complications. Of the many factors that affect the gastrointestinal tract mucosal integrity, intramural pressure, and bacterial flora-produced intraluminal gas interact to produce PI. If the condition is accompanied by bowel ischemia, portomesenteric venous gas, metabolic acidosis, and abdominal sepsis, or if PI is severe in extent immediate surgical intervention is indicated. The described case supports that a mechanical rather than a bacterial etiology underlies the pathogenesis of PI

Effect of delayed hospitalization on 3-year clinical outcomes according to renal function in patients with non-ST-segment elevation myocardial infarction

Background: We evaluated the effect of delayed hospitalization (symptom-to-door time [STD] ≥ 24 h) on 3-year clinical outcomes according to renal function in patients with non-ST-segment elevation myocardial infarction (NSTEMI) undergoing new-generation drug-eluting stent (DES) implantation. Methods: A total of 4513 patients with NSTEMI were classified into chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2, n = 1118) and non-CKD (eGFR ≥ 60 mL/min/1.73 m2, n = 3395) groups. They were further sub-classified into groups with (STD ≥ 24 h) and without (STD < 24 h) delayed hospitalization. The primary outcome was the occurrence of major adverse cardiac and cerebrovascular events (MACCE), defined as all-cause death, recurrent myocardial infarction, any repeat coronary revascularization, and stroke. The secondary outcome was stent thrombosis (ST). Results: After multivariable-adjusted and propensity score analyses, the primary and secondary clinical outcomes were similar in patients with or without delayed hospitalization in both CKD and non-CKD groups. However, in both the STD < 24 h and STD ≥ 24 h groups, MACCE (p < 0.001 and p < 0.006, respectively) and mortality rates were significantly higher in the CKD group than in the non-CKD group. However, ST rates were similar between the CKD and non-CKD groups and between the STD < 24 h and STD ≥ 24 h groups. Conclusions: Chronic kidney disease appears to be a much more important determinant of MACCE and mortality rates than STD in patients with NSTEMI

Xylitol production is increased by expression of codon-optimized Neurospora crassa xylose reductase gene in Candida tropicalis

Xylose reductase (XR) is the first enzyme in d-xylose metabolism, catalyzing the reduction of d-xylose to xylitol. Formation of XR in the yeast Candida tropicalis is significantly repressed in cells grown on medium that contains glucose as carbon and energy source, because of the repressive effect of glucose. This is one reason why glucose is not a suitable co-substrate for cell growth in industrial xylitol production. XR from the ascomycete Neurospora crassa (NcXR) has high catalytic efficiency; however, NcXR is not expressed in C. tropicalis because of difference in codon usage between the two species. In this study, NcXR codons were changed to those preferred in C. tropicalis. This codon-optimized NcXR gene (termed NXRG) was placed under control of a constitutive glyceraldehyde-3-phosphate dehydrogenase (GAPDH) promoter derived from C. tropicalis, and integrated into the genome of xylitol dehydrogenase gene (XYL2)-disrupted C. tropicalis. High expression level of NXRG was confirmed by determining XR activity in cells grown on glucose medium. The resulting recombinant strain, LNG2, showed high XR activity (2.86 U (mg of protein)−1), whereas parent strain BSXDH-3 showed no activity. In xylitol fermentation using glucose as a co-substrate with xylose, LNG2 showed xylitol production rate 1.44 g L−1 h−1 and xylitol yield of 96% at 44 h, which were 73 and 62%, respectively, higher than corresponding values for BSXDH-3 (rate 0.83 g L−1 h−1; yield 59%)

The Skin Antiseptic agents at Vaginal dElivery (SAVE) trial: study protocol for a randomized controlled trial

Background Cleansing of the vulva and perineum is recommended during preparation for vaginal delivery, and special attention is paid to cleansing before episiotomy because episiotomy is known to increase the risk of perineal wound infection and/or dehiscence. However, the optimal method of perineal cleansing has not been established, including the choice of antiseptic agent. To address this issue, we designed a randomized controlled trial to examine whether skin preparation with chlorhexidine-alcohol is superior to povidone-iodine for the prevention of perineal wound infection after vaginal delivery. Methods In this multicenter randomized controlled trial, term pregnant women who plan to deliver vaginally after episiotomy will be enrolled. The participants will be randomly assigned to use antiseptic agents for perineal cleansing (povidone-iodine or chlorhexidine-alcohol). The primary outcome is superficial or deep perineal wound infection within 30 days after vaginal delivery. The secondary outcomes are the length of hospital stay, physician office visits, or hospital readmission for infection-related complications, endometritis, skin irritations, and allergic reactions. Discussion This study will be the first randomized controlled trial aiming to determine the optimal antiseptic agent for the prevention of perineal wound infections after vaginal delivery. Trial registration ClinicalTrials.gov NCT05122169. First submitted date on 8 November 2021. First posted date on 16 November 202

The Effect of Cyclooxygenase-2 Expression on Tumor Volume Response in Patients Treated with Radiotherapy for Uterine Cervical Cancer

We investigated the correlation between Cyclooxygenase-2 (COX-2) expression and the tumor response in patients with cervical cancer that were treated with curative radiotherapy (RT). Fifty-seven patients with squamous cell carcinoma were treated with concurrent radiochemotherapy (CRCT, n=29) or RT alone (n=28). The response of each patient was evaluated by three serial Magnetic Resonance Imaging examinations: before the start of RT, at four weeks after the start of RT (mid-RT) and at four weeks after the completion of RT (post-RT). Forty-three patients had positive COX-2 expression. The COX-2 negative patients achieved a higher rate of complete response (CR) at mid-RT than did the COX-2 positive patients (28.6% vs. 7.0%, P=0.054), but not at post-RT (64.3% vs. 69.8%). The initial tumor volume was a significant predictor of CR at mid-RT (P=0.003) and post-RT (P=0.004). The multivariate analysis showed that the initial tumor volume (at mid-RT and post-RT) and CRCT (at post-RT) were significant predictors of CR; however, the COX-2 expression was not. In conclusion, the COX-2 expression status has no significant correlation with the tumor response. Further studies on the changes in COX-2 expression levels during RT may be helpful for determination of its role in the tumor response to treatment and patient prognosis

Active pulmonary tuberculosis and latent tuberculosis infection among homeless people in Seoul, South Korea: a cross-sectional study

Background : The aim of this study was to determine the prevalence rate of latent TB infection (LTBI) and active TB among homeless in Seoul metropolitan city, South Korea, and to compare the TB burden among homeless people with that of a control group. Methods : The homeless participants were recruited from five sites between October 30, 2009 and April 12, 2010. LTBI was diagnosed through the QuantiFERON(R) TB Gold In-Tube(QFT-GIT) assay and a tuberculin skin test(TST) and, and active PTB was diagnosed based on chest radiography. Results : Among 313 participants, the prevalence of LTBI was 75.9% (95% CI, 71.1-80.8%) and 79.8% (95% CI, 74.9-84.7%) based on a QFT-GIT assay and the TST, respectively, and that of active PTB was 5.8% (95% CI, 3.2-8.3%). The prevalence of LTBI among homeless participants was about five times higher than controls. Also, the age-specific prevalence rate ratio of active PTB was as high as 24.86. Conclusions : The prevalence rate of LTBI as well as active PTB among homeless people was much higher than that of the general population in South Korea. Thus, adequate strategies to reduce the TB burden among homeless people are needed.Peer Reviewe