Use of NASA Bioreactor in Engineering Tissue for Bone Repair

This study was proposed in search for a new alternative for bone replacement or repair. Because the systems commonly used in repair of bony defects form bone by going through a cartilaginous phase, implantation of a piece of cartilage could enhance the healing process by having a more advanced starting point. However, cartilage has seldom been used to replace bone due, in part, to the limitations in conventional culture systems that did not allow production of enough tissue for implants. The NASA-developed bioreactors known as STLV (Slow Turning Lateral Vessel) provide homogeneous distribution of cells, nutrients, and waste products, with less damaging turbulence and shear forces than conventional systems. Cultures under these conditions have higher growth rates, viability, and longevity, allowing larger "tissue-like" aggregates to form, thus opening the possibilities of producing enough tissue for implantation, along with the inherent advantages of in vitro manipulations. To assure large numbers of cells and to eliminate the use of timed embryos, we proposed to use an immortalized mouse limb bud cell line as the source of cells

Low density lipoprotein cholesterol control status among Canadians at risk for cardiovascular disease: findings from the Canadian Primary Care Sentinel Surveillance Network Database

Background To determine the prevalence of uncontrolled LDL-C in patients with high cardiovascular disease (CVD) risks across Canada and to examine its related factors. Methods Non-pregnant adults >20 years-old, who had a lipid test completed between January 1, 2009 and December 31, 2011 and were included in the Canadian Primary Care Surveillance Network (CPCSSN) database were studied. The Framingham-Risk-Score was calculated to determine the risk levels. A serum LDL-C level of >2.0 mmol/L was considered as being poorly controlled. Patients with a previous record of a cerebrovascular accident, peripheral artery disease, or an ischemic heart disease were regarded as those under secondary prevention. Logistic regression modeling was performed to examine the factors associated with the LDL-C control. Results A total of 6,405 high-risk patients were included in the study and, of this population, 68 % had a suboptimal LDL-C, which was significantly associated with the female gender (OR: 3.26; 95 % CI: 2.63–4.05, p < 0.0001) and no medication therapy (OR: 6.31, 95 % CI: 5.21–7.65, p < 0.0001). Those with comorbidities of diabetes, hypertension, obesity, and smokers had a better LDL-C control. Rural residents (OR: 0.64, 95 % CI: 0.52–0.78, p < 0.0001), and those under secondary prevention (OR: 0.42; 95 % CI: 0.35–0.51, p < 0.0001), were also more likely to have a better LDL-C control. Conclusion A high proportion of high-cardiac risk patients in Canadian primary care settings have suboptimal LDL-C control. A lack of medication therapy appears to be the major contributing factor to this situation

An Investigation of Cancer Rates in the Argentia Region, Newfoundland and Labrador: An Ecological Study

Background. The Argentia region of Newfoundland and Labrador, Canada, was home to a US naval base during a 40-year period between the 1940s and the 1990s. Activities on the base resulted in contamination of the soil and groundwater in the region with chemicals such as heavy metals and dioxins, and residents have expressed concern about higher rates of cancer in their community. This study investigated the rate of cancer diagnosis that is disproportionately high in the Argentia region. Methods. Cases of cancer diagnosed between 1985 and 2011 were obtained for the Argentia region, two comparison communities, and the province of Newfoundland and Labrador. Crude and age-standardized incidence rates of cancer diagnosis were calculated and compared. The crude incidence rate was adjusted for differences in age demographics using census data, and age-standardized incidence rates were compared. Results. Although the Argentia region had a higher crude rate of cancer diagnosis, the age-standardized incidence rate did not differ significantly from the comparison communities or the provincial average. Argentia has an aging population, which may have influenced the perception of increased cancer diagnosis in the community. Conclusions. We did not detect an increased burden of cancer in the Argentia region

Six-year time-trend analysis of dyslipidemia among adults in Newfoundland and Labrador: findings from the laboratory information system between 2009 and 2014

Background: Dyslipidemia, an increased level of total cholesterol (TC), triglycerides (TG), low-density-lipoprotein cholesterol (LDL-C) and decreased level of high-density-lipoprotein cholesterol (HDL-C), is one of the most important risk factors for cardiovascular disease. We examined the six-year trend of dyslipidemia in Newfoundland and Labrador (NL), a Canadian province with a historically high prevalence of dyslipidemia. Methods: A serial cross-sectional study on all of the laboratory lipid tests available from 2009 to 2014 was performed. Dyslipidemia for every lipid component was defined using the Canadian Guidelines for the Diagnosis and Treatment of Dyslipidemia. The annual dyslipidemia rates for each component of serum lipid was examined. A fixed and random effect model was applied to adjust for confounding variables (sex and age) and random effects (residual variation in dyslipidemia over the years and redundancies caused by individuals being tested multiple times during the study period). Results: Between 2009 and 2014, a total of 875,208 records (mean age: 56.9 ± 14.1, 47.6% males) containing a lipid profile were identified. The prevalence of HDL-C and LDL-C dyslipidemia significantly decreased during this period (HDL-C: 35.8% in 2009 [95% CI 35.5-36.1], to 29.0% in 2014 [95% CI: 28.8-29.2], P = 0.03, and LDL-C: 35.2% in 2009 [95% CI: 34.9-35.4] to 32.1% in 2014 [95% CI: 31.9-32.3], P = 0.02). A stratification by sex, revealed no significant trend for any lipid element in females; however, in men, the previously observed trends were intensified and a new decreasing trend in dyslipidemia of TC was appeared (TC: 34.1% [95% CI 33.7-34.5] to 32.3% [95%CI: 32.0-32.6], p < 0.02, HDL-C: 33.8% (95%CI: 33.3-34.2) to 24.0% (95% CI: 23.7-24.3)], P < 0.01, LDL-C: 32.9% (95%CI:32.5-33.3) to 28.6 (95%CI: 28.3-28.9), P < 0.001). Adjustment for confounding factors and removing the residual noise by modeling the random effects did not change the significance. Conclusion: This study demonstrates a significant downward trend in the prevalence of LDL-C, HDL-C, and TC dyslipidemia, exclusively in men. These trends could be the result of males being the primary target for cardiovascular risk management

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research