A randomized,double-blind,multicenter, placebo-controlled study to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D

This randomized, double-blind, placebo-controlled phase III study was conducted to assess the efficacy and safety of oral calcitonin (SMC021) for the treatment of postmenopausal osteoporosis. A total of 4665 postmenopausal women with osteoporosis were randomized 1:1 to receive calcium and vitamin D plus either SMC021 tablets (0.8 mg/d) or placebo for 36 months. The primary endpoint was the proportion of patients with a new vertebral fracture.The two groups were well balanced at baseline with regards to demographic and clinical data. No effect of SMC021 on preventing new vertebral fractures was observed, nor was any effect seen on new hip or non-vertebral fractures. Women receiving SMC021 had a mean 1.02% (± 0.12%) increase in lumbar spine bone mineral density (BMD) compared with a mean 0.18% (± 0.12%) increase in the placebo group by the end of the study (p < 0.0001). Similarly, small increases in BMD were observed at the femoral neck and hip in both groups. Levels of the biomarkers of bone turnover, urinary CTX-I and CTX-II, were 15% lower in the SMC021 group than in the placebo arm at 12 and 24 months, but not at 36 months. No change in quality of life between groups, assessed by the Qualeffo-14 questionnaire, was observed in either group between baseline and month 36. Pharmacokinetics analysis confirmed exposure to SMC021, but the drug levels were markedly lower than expected.Approximately 92% of subjects in each treatment group experienced an adverse event (AE), the majority of which were mild or moderate in intensity. AEs associated with SMC021 were primarily of gastrointestinal origin and included nausea, vomiting and abdominal pain, as well as hot flushes which were the reason for the slightly higher drop-out rate in the active treatment arm compared to placebo. The number of severe AEs was low in both groups. Thirty-five deaths were reported but none were considered treatment-related.Due to the lack of efficacy in preventing fractures, the development of the orally formulated calcitonin was terminated despite the promising results in earlier studies.     

Cervicovaginal shedding of hepatitis C viral RNA is associated with the presence of menstrual or other blood in cervicovaginal fluids

BackgroundThe role of sexual activity in hepatitis C virus (HCV) transmission remains controversial. Studies to date have not explored the relationship between HCV shedding in cervicovaginal fluids and the presence of menstrual or other blood.ObjectivesSince cross-sectional studies may underestimate the prevalence of viral shedding, we performed a 56-day longitudinal study of cervical HCV shedding.Study designWomen self-collected cervicovaginal swabs for 56 consecutive days, while keeping a diary of menses and genital symptoms. Swabs were tested for HCV RNA and cellular DNA by quantitative PCR, and hemoglobin by spectrophotometry.ResultsSixteen women contributed a total of 701 cervicovaginal swabs (mean collection period 48 days, range 18–56). Detection of HCV RNA was associated with detection of hemoglobin. Premenopausal women were more likely than post-menopausal women to have HCV RNA detected in cervicovaginal fluids. For premenopausal women, detection of HCV RNA was more likely during menstruation (OR = 56.4) or when hemoglobin was detected in cervicovaginal fluids, even if menstruation was not occurring (OR = 35.4). No woman post-hysterectomy had HCV RNA detected in cervicovaginal fluids on any day, regardless of whether hemoglobin was detected.ConclusionsOur findings are consistent with a low likelihood of sexual transmission of HCV. The results suggest that shedding of HCV RNA in the female genital tract is associated with the presence of blood, and requires the presence of a cervix. Clinicians should consider advising premenopausal women who are concerned about transmitting infection that infectivity may increase during menstruation.     

Eligibility of patients with renal impairment for Phase I trials: Time for a rethink?

Since the inception of Phase I clinical trials in cancer, patients with renal dysfunction have commonly been excluded from participation because of a poor outlook. Most cancer drugs are approved with limited information on the pharmacokinetics and/or pharmacodynamics of the drugs in patients with renal dysfunction, and no formal renal dysfunction study is ever undertaken. Patients with asymptomatic mild to moderate renal dysfunction pose an increasingly frequent challenge for clinicians. In this paper, we discuss that a subset of patients with asymptomatic mild to moderate renal impairment might be appropriately entered into selected Phase I trials. This will provide physicians timely data of the new agents in this patient population and increase patients’ access to experimental treatments.     

Dynamic chromatin loops bridge health and disease in the nuclear landscape

The genome is dynamically organized in the nuclear space in a manner that reflects and influences nuclear functions. Developmental processes that govern the formation and maintenance of epigenetic memories are also tightly linked to adaptive changes in the physical and functional landscape of the nuclear architecture. Biological and biophysical principles governing the three-dimensional folding of chromatin are therefore central to our understanding of epigenetic regulation during adaptive responses and in complex diseases, such as cancer. Accumulating evidence points to the direction that global alterations in nuclear architecture and chromatin folding conspire with unstable epigenetic states of the primary chromatin fiber to drive the phenotypic plasticity of cancer cells.     

Intraosseous temperature changes during the use of piezosurgical inserts in vitro

This study concerns intraosseous temperature changes during the use of piezosurgical inserts. On six fresh pig jaws heated to body temperature (36 °C), osteotomies and osteoplasties were performed in vitro with the Piezosurgery^® 3 device (Mectron, Carasco, Italy) and various inserts. The intraosseous temperature increases were measured at a depth of 3 mm and at a distance of 1 mm from the working site using nickel–chromium/nickel temperature sensors. 20 °C Ringer's solution was used for cooling in an initial test series and 10 °C Ringer's in a second series. The processed bone was examined using digital volume tomography images to determine the ratio of cortical to cancellous bone thickness. Mean temperature increases of 4.4–10.9 °C were found; maximum temperature peaks were over 47 °C for an average of only 8.5 s. The type of piezosurgical insert had a marked influence on intraosseous temperature generation (p = 0.026); the thickness of the cortical bone and the temperature of the coolant did not. Coolant temperature had an influence on the bone cooling time (p = 0.013). The results show that correct use of the piezosurgery device does not give rise to prolonged temperature increases over 47 °C and hence does not cause any irreversible thermal damage in the bone.     

The efficacy and safety of gemcitabine-based induction chemotherapy for locally advanced nasopharyngeal carcinoma treated with concurrent chemoradiation: A meta-analysis

Objectives:To assess the efficacy and toxicity of gemcitabine-based induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal carcinoma (LA-NPC).Methods:Both observational studies (OBS) and randomized controlled trials (RCT) were included in the meta-analysis. Systematic online searches were conducted in Web of Sciences, PubMed, Embase, meeting proceedings and ClinicalTrials.gov from the inception to May 25, 2020. The primary endpoint of interest was overall survival.Results:five OBSs and 2 RCTs including 1680 patients were incorporated in the analysis. The evidence from the RCTs showed that adding gemcitabine-based induction chemotherapy to CCRT significantly improved progression free survival (hazard ratio (HR): 0.60, 95% confidence interval (CI): 0.40–0.88; P = .010; chi square P = .25; I² = 24%) and overall survival (HR: 0.47; 95% CI: 0.28–0.80; P = 0.005; chi square P = .49, I² = 0%) and was related to a higher risk of hematological toxicities. Furthermore, based on the data of OBSs, overall survival (HR: 0.52; 95% CI: 0.31–0.88; P = .02; chi square P = .37, I² = 6%) was significantly improved in patients treated with gemcitabine-based induction chemotherapy compared to those treated with taxane-based induction chemotherapy. However, the progression free survival (HR: 0.67; 95% CI: 0.45–1.01; P = .06; chi square P = .74; I² = 0%) showed no significant difference.Conclusions:For LA-NPC patients, adding gemcitabine-based induction chemotherapy to CCRT significantly improved overall survival and progression free survival with a higher risk of hematological toxicities when compared to CCRT alone. Also, gemcitabine-based regimen could be used as an alternative induction chemotherapy regimen to taxane-based regimen in the treatment of LA-NPC.     

Vaxvec: The first web-based recombinant vaccine vector database and its data analysis

A recombinant vector vaccine uses an attenuated virus, bacterium, or parasite as the carrier to express a heterologous antigen(s). Many recombinant vaccine vectors and related vaccines have been developed and extensively investigated. To compare and better understand recombinant vectors and vaccines, we have generated Vaxvec (http://www.violinet.org/vaxvec), the first web-based database that stores various recombinant vaccine vectors and those experimentally verified vaccines that use these vectors. Vaxvec has now included 59 vaccine vectors that have been used in 196 recombinant vector vaccines against 66 pathogens and cancers. These vectors are classified to 41 viral vectors, 15 bacterial vectors, 1 parasitic vector, and 1 fungal vector. The most commonly used viral vaccine vectors are double-stranded DNA viruses, including herpesviruses, adenoviruses, and poxviruses. For example, Vaxvec includes 63 poxvirus-based recombinant vaccines for over 20 pathogens and cancers. Vaxvec collects 30 recombinant vector influenza vaccines that use 17 recombinant vectors and were experimentally tested in 7 animal models. In addition, over 60 protective antigens used in recombinant vector vaccines are annotated and analyzed. User-friendly web-interfaces are available for querying various data in Vaxvec. To support data exchange, the information of vaccine vectors, vaccines, and related information is stored in the Vaccine Ontology (VO). Vaxvec is a timely and vital source of vaccine vector database and facilitates efficient vaccine vector research and development.