High-grade osteosarcoma is a primary malignant bone tumour mainly affecting children and young adults. The European and American Osteosarcoma Study (EURAMOS)-1 is a collaboration of four study groups ...aiming to improve outcomes of this rare disease by facilitating randomised controlled trials.
Patients eligible for EURAMOS-1 were aged ≤40 years with M0 or M1 skeletal high-grade osteosarcoma in which case complete surgical resection at all sites was deemed to be possible. A three-drug combination with methotrexate, doxorubicin and cisplatin was defined as standard chemotherapy, and between April 2005 and June 2011, 2260 patients were registered. We report survival outcomes and prognostic factors in the full cohort of registered patients.
For all registered patients at a median follow-up of 54 months (interquartile range: 38–73) from biopsy, 3-year and 5-year event-free survival were 59% (95% confidence interval CI: 57–61%) and 54% (95% CI: 52–56%), respectively. Multivariate analyses showed that the most adverse factors at diagnosis were pulmonary metastases (hazard ratio HR = 2.34, 95% CI: 1.95–2.81), non-pulmonary metastases (HR = 1.94, 95% CI: 1.38–2.73) or an axial skeleton tumour site (HR = 1.53, 95% CI: 1.10–2.13). The histological subtypes telangiectatic (HR = 0.52, 95% CI: 0.33–0.80) and unspecified conventional (HR = 0.67, 95% CI: 0.52–0.88) were associated with a favourable prognosis compared with chondroblastic subtype. The 3-year and 5-year overall survival from biopsy were 79% (95% CI: 77–81%) and 71% (95% CI: 68–73%), respectively. For patients with localised disease at presentation and in complete remission after surgery, having a poor histological response was associated with worse outcome after surgery (HR = 2.13, 95% CI: 1.76–2.58). In radically operated patients, there was no good evidence that axial tumour site was associated with worse outcome.
In conclusion, data from >2000 patients registered to EURAMOS-1 demonstrated survival rates in concordance with institution- or group-level osteosarcoma trials. Further efforts are required to drive improvements for patients who can be identified to be at higher risk of adverse outcome. This trial reaffirms known prognostic factors, and owing to the large numbers of patients registered, it sheds light on some additional factors to consider.
•Osteosarcoma is a rare disease, and treatment can only improve with international collaboration.•We have assembled prospectively collected data from treatments of all the patients in the intercontinental European and American Osteosarcoma Study-1 protocol.•These consistently treated patients provided a strong data set for reporting survival outcomes and reporting on prognostic factors.•The trial reaffirms known prognostic factors, and the most adverse factors were metastases and tumours in the axial skeleton.•Owing to the large numbers of patients registered, light is shed on some additional factors to be considered. Around seven in ten patients were still alive five years after diagnosis.
Evolving literature suggests that the epidemic of prescription opioid use affects the transplant population. We examined a novel database wherein national U.S. transplant registry records were linked ...to a large pharmaceutical claims warehouse (2007‐2015) to characterize prescription opioid use before and after kidney transplant, and associations (adjusted hazard ratio, 95% LCLaHR95% UCL) with death and graft loss. Among 75 430 eligible patients, 43.1% filled opioids in the year before transplant. Use was more common among recipients who were women, white, unemployed, publicly insured, and with longer pretransplant dialysis. Of those with the highest level of pretransplant opioid use, 60% continued high‐level use posttransplant. Pretransplant opioid use had graded associations with one‐year posttransplant outcomes; the highest‐level use predicted 46% increased risk of death (aHR 1.281.461.66) and 28% increased risk of all‐cause graft failure (aHR 1.171.281.41). Effects of high‐level opioid use in the first year after transplant were stronger, predicting twice the risk of death (aHR 1.932.242.60) and 68% higher all‐cause graft failure risk (aHR 1.501.681.89) over the subsequent year; increased risk persisted over five years. While associations may, in part, reflect underlying conditions or behaviors, opioid use history is relevant in assessing and providing care to transplant candidates and recipients.
Examination of integrated US transplant registry data and records from a nationwide pharmacy claims warehouse demonstrates that pretransplant prescription opioid use is associated with a 45% increased risk of death and 28% increased risk of all‐cause graft loss in the first year posttransplant, that most high‐level opioid users continue to fill at high levels in the year after transplant, and that posttransplant prescription opioid use predicts a twofold increased risk of death over the subsequent year.
To examine several poorly understood or contentious aspects of the antibacterial activity of silver (Ag(+)), including its cidality, mode of action, the prevalence of resistance amongst clinical ...staphylococcal isolates and the propensity for Staphylococcus aureus to develop Ag(+) resistance.
The effects of Ag(+) on the viability, macromolecular synthesis and membrane integrity of S. aureus SH1000 were assessed using established methodology. Silver nitrate MICs were determined for a collection of staphylococcal isolates (n = 1006) collected from hospitals across Europe and Canada between 1997 and 2010. S. aureus biofilms were grown using the Calgary Biofilm Device. To examine the in vitro development of staphylococcal resistance to Ag(+), bacteria were subjected to continuous subculture in the presence of sub-MIC concentrations of Ag(+).
Silver was bactericidal against S. aureus in buffered solution, but bacteriostatic in growth medium, and was unable to eradicate staphylococcal biofilms in vitro. Challenge of S. aureus with Ag(+) caused rapid loss of membrane integrity and inhibition of the major macromolecular synthetic pathways. All clinical staphylococcal isolates were susceptible to ≤ 16 mg/L silver nitrate and prolonged exposure (42 days) to Ag(+) in vitro failed to select resistant mutants.
The rapid and extensive loss of membrane integrity observed upon challenge with Ag(+) suggests that the antibacterial activity results directly from damage to the bacterial membrane. The universal susceptibility of staphylococci to Ag(+), and failure to select for resistance to Ag(+), suggest that silver compounds remain a viable option for the prevention and treatment of topical staphylococcal infections.
OPTN/SRTR 2016 Annual Data Report: Economics Schnitzler, M. A.; Skeans, M. A.; Axelrod, D. A. ...
American journal of transplantation,
January 2018, 2018-01-00, 20180101, Letnik:
18, Številka:
S1
Journal Article
Recenzirano
Odprti dostop
Medicare costs vary for solid organ transplant recipients by outcome: survival with graft function, survival with graft failure, and death. Average per‐person per‐year reimbursement was $75 thousand ...for kidney recipients who survived the first year posttransplant with a functioning graft, $171 thousand for those who required a return to dialysis or retransplant, and $350 thousand for those who died with function. For pancreas recipients: $105 thousand for those who survived the first year with a functioning graft, $120 thousand for those who survived pancreas failure, and $443 thousand for those who died with function. For liver recipients: $154 thousand for those who survived with a functioning graft, $388 thousand for those who required retransplant, and $740 thousand who died with function. For intestine recipients: $301 thousand for those who survived with a functioning graft and $1 million for those who died with function. For heart recipients: $272 thousand for those who survived with a functioning graft and $1.2 million for those who died with function. For lung recipients: $196 thousand for those who survived with a functioning graft, $642 thousand for those who required retransplant, and $761 thousand for those who died with function.
ABO compatibility is important for kidney transplantation, with longer waitlist times for blood group B kidney transplant candidates. However, kidneys from non-A1 (eg, A2) subtype donors, which ...express less A antigen, can be safely transplanted into group B recipients. ABO subtyping is routinely performed using anti-A1 lectin, but DNA-based genotyping is also possible. Here, we compare lectin and genotyping testing. Lectin and genotype subtyping was performed on 554 group A deceased donor samples at 2 transplant laboratories. The findings were supported by 2 additional data sets of 210 group A living kidney donors and 124 samples with unclear lectin testing sent to a reference laboratory. In deceased donors, genotyping found 65% more A2 donors than lectin testing, most with weak lectin reactivity, a finding supported in living donors and samples sent for reference testing. DNA sequencing and flow cytometry showed that the discordances were because of several factors, including transfusion, small variability in A antigen levels, and rare ABO∗A2.06 and ABO∗A2.16 sequences. Although lectin testing is the current standard for transplantation subtyping, genotyping is accurate and could increase A2 kidney transplant opportunities for group B candidates, a difference that should reduce group B wait times and improve transplant equity.
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The conservation status of small cetaceans has significantly worsened since the 1980s, when the baiji was the only species of small cetacean listed as Endangered by IUCN. Now the baiji is almost ...certainly extinct and 13 other species, subspecies, or populations (hereafter units-to-conserve or units) of small cetaceans are listed as Critically Endangered (CR) on the IUCN Red List. Bycatch is the main threat to 11 of the CR units. Entanglement in gillnets contributed to the extinction of the baiji and is responsible for the imminent extinction of the vaquita. Unfortunately, there is no simple technical solution to the problem of bycatch of small cetaceans. If the 8 CR units with 100 or fewer remaining individuals are to be saved, conservation zones must be established where gillnets are eliminated and bans on their use are strictly enforced. Recent experience with the vaquita in Mexico demonstrates that enforcement of such conservation zones can be very difficult. Ineffective enforcement is also a problem for at least 4 of the other CR units. Time is very short and, unless major efforts are made now to address the bycatch problem, the prospects for CR small cetaceans and other at-risk aquatic megafauna are grim. The ultimate long-term solution to the bycatch problem is the development of efficient, inexpensive, alternative fishing gear that can replace gillnets without jeopardizing the livelihoods of fishermen. Good fishery governance and the direct involvement of fishing communities are also essential to the successful conservation of most threatened populations of small cetaceans.
OPTN/SRTR 2019 Annual Data Report: Econ Schnitzler, M.A.; Miller, J.; Skeans, M.A. ...
American journal of transplantation,
02/2021, Letnik:
21, Številka:
S2
Journal Article
Recenzirano
Odprti dostop
Resource utilization metrics vary widely across solid organ transplant modalities. Average length of stay (LOS) for kidney transplant has declined by 15.1%, from 8.7 days in 2008 to 7.4 days in 2019. ...A similar decline in LOS of 17.5% was seen in pancreas transplant. LOS for liver transplant remained relatively stable over this period, while LOS was most variable for intestine transplant, with a high of 70.9 days in 2008 and 26.2% lower (52.3 days) in 2011. However, LOS for both heart and lung transplant have generally risen through 2019. Pediatric patients generally experienced the longest LOS across all organs. Large variation in LOS by diagnosis was seen across organs, with the shortest LOS in kidney for glomerulonephritis, liver for hepatocellular carcinoma, and lung for obstructive pulmonary disease. Reported readmission during the first year post‐transplant in 2018 varied from a low of 39.9% in heart, followed by 48.1% in kidney, 52.1% in lung, 59.7% in liver, and 61.8% in pancreas, to a high of 95.6% in intestine. In kidney, liver, and heart transplant, Asian recipients had the fewest readmissions across all years.
ABSTRACT
The shoots of cultivated tomato (Lycopersicon esculentum cv. T5) wilt if their roots are exposed to chilling temperatures of around 5 °C. Under the same treatment, a chilling‐tolerant ...congener (Lycopersicon hirsutum LA 1778) maintains shoot turgor. To determine the physiological basis of this differential response, the effect of chilling on both excised roots and roots of intact plants in pressure chambers were investigated. In excised roots and intact plants, root hydraulic conductance declined with temperature to nearly twice the extent expected from the temperature dependence of the viscosity of water, but the response was similar in both species. The species differed markedly, however, in stomatal behaviour: in L. hirsutum, stomatal conductance declined as root temperatures were lowered, whereas the stomata of L. esculentum remained open until the roots reached 5 °C, and the plants became flaccid and suffered damage. Grafted plants with the shoots of one genotype and roots of another indicated that the differential stomatal behaviour during root chilling has distinct shoot and root components.
Blood pressure and end-stage renal disease in men Klag, M J; Whelton, P K; Randall, B L ...
New England journal of medicine/The New England journal of medicine,
01/1996, Letnik:
334, Številka:
1
Journal Article
Recenzirano
Odprti dostop
End-stage renal disease in the United States creates a large burden for both individuals and society as a whole. Efforts to prevent the condition require an understanding of modifiable risk factors.
...We assessed the development of end-stage renal disease through 1990 in 332,544 men, 35 to 57 years of age, who were screened between 1973 and 1975 for entry into the Multiple Risk Factor Intervention Trial (MRFIT). We used data from the national registry for treated end-stage renal disease of the Health Care Financing Administration and from records on death from renal disease from the National Death Index and the Social Security Administration.
During an average of 16 years of follow-up, 814 subjects either died of end-stage renal disease or were treated for that condition (15.6 cases per 100,000 person-years of observation). A strong, graded relation between both systolic and diastolic blood pressure and end-stage renal disease was identified, independent of associations between the disease and age, race, income, use of medication for diabetes mellitus, history of myocardial infarction, serum cholesterol concentration, and cigarette smoking. As compared with men with an optimal level of blood pressure (systolic pressure < 120 mm Hg and diastolic pressure < 80 mm Hg), the relative risk of end-stage renal disease for those with stage 4 hypertension (systolic pressure > or = 210 mm Hg or diastolic pressure > or = 120 mm Hg) was 22.1 (P < 0.001). These relations were not due to end-stage renal disease that occurred soon after screening and, in the 12,866 screened men who entered the MRFIT study, were not changed by taking into account the base-line serum creatinine concentration and urinary protein excretion. The estimated risk of end-stage renal disease associated with elevations of systolic pressure was greater than that linked with elevations of diastolic pressure when both variables were considered together.
Elevations of blood pressure are a strong independent risk factor for end-stage renal disease; interventions to prevent the disease need to emphasize the prevention and control of both high-normal and high blood pressure.
The purpose of this study was to compare self-reported symptoms for exercise-induced asthma (EIA) to postexercise challenge pulmonary function test results in elite athletes.
Elite athletes (N = 158; ...83 men and 75 women; age: 22 +/- 4.4 yr) performed pre- and post-exercise spirometry and were grouped according to postexercise pulmonary function decrements (PFT-positive, PFT-borderline, and PFT-normal for EIA). Before the sport/environment specific exercise challenge, subjects completed an EIA symptoms-specific questionnaire.
Resting FEV1 values were above predicted values (114--121%) and not different between groups. Twenty-six percent of the study population demonstrated >10% postexercise drop in FEV1 and 29% reported two or more symptoms. However, the proportion of PFT-positive and PFT-normal athletes reporting two or more symptoms was not different (39% vs. 41%). Postrace cough was the most reported symptom, reported significantly more frequently for PFT-positive athletes (P < 0.05). Sensitivity/specificity analysis demonstrated a lack of effectiveness of self-reported symptoms to identify PFT-positive or exclude PFT-normal athletes. Postexercise lower limit reference ranges (MN-2SDs) were determined from normal athletes for FEV1, FEF25--75% and PEF to be -7%, -12.5%, and -18%, respectively.
Although questionnaires provide reasonable estimates of EIA prevalence among elite cold-weather athletes, the use of self-reported symptoms for EIA diagnosis in this population will likely yield high frequencies of both false positive and false negative results. Diagnosis should include spirometry using an exercise/environment specific challenge in combination with the athlete's history of asthma symptoms.
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