CLIMATE CHANGE AND VIOLENT CONFLICT Scheffran, Jürgen; Brzoska, Michael; Kominek, Jasmin ...
Science (American Association for the Advancement of Science),
05/2012, Letnik:
336, Številka:
6083
Journal Article
Recenzirano
Current debates over the relation between climate change and conflict originate in a lack of data, as well as the complexity of pathways connecting the two phenomena.
To compare three-drug chemotherapy with cisplatin, doxorubicin, and methotrexate with four-drug chemotherapy with cisplatin, doxorubicin, methotrexate, and ifosfamide for the treatment of ...osteosarcoma. To determine whether the addition of muramyl tripeptide (MTP) to chemotherapy enhances event-free survival (EFS) and overall survival in newly diagnosed patients with osteosarcoma.
Six hundred sixty-two patients with osteosarcoma without clinically detectable metastatic disease and whose disease was considered resectable received one of four prospectively randomized treatments. All patients received identical cumulative doses of cisplatin, doxorubicin, and methotrexate and underwent definitive surgical resection of primary tumor. Patients were randomly assigned to receive or not to receive ifosfamide and/or MTP in a 2 x 2 factorial design. The primary end points for analysis were EFS and overall survival.
In the current analysis, there was no evidence of interaction, and we were able to examine each intervention separately. The chemotherapy regimens resulted in similar EFS and overall survival. There was a trend toward better EFS with the addition of MTP (P = .08). The addition of MTP to chemotherapy improved 6-year overall survival from 70% to 78% (P = .03). The hazard ratio for overall survival with the addition of MTP was 0.71 (95% CI, 0.52 to 0.96).
The addition of ifosfamide to cisplatin, doxorubicin, and methotrexate did not enhance EFS or overall survival for patients with osteosarcoma. The addition of MTP to chemotherapy resulted in a statistically significant improvement in overall survival and a trend toward better EFS.
Mass spectrometry-based metabolomics approaches can enable detection and quantification of many thousands of metabolite features simultaneously. However, compound identification and reliable ...quantification are greatly complicated owing to the chemical complexity and dynamic range of the metabolome. Simultaneous quantification of many metabolites within complex mixtures can additionally be complicated by ion suppression, fragmentation and the presence of isomers. Here we present guidelines covering sample preparation, replication and randomization, quantification, recovery and recombination, ion suppression and peak misidentification, as a means to enable high-quality reporting of liquid chromatography- and gas chromatography-mass spectrometry-based metabolomics-derived data.
Objectives
To compare the diagnostic accuracy of 2-
18
Ffluoro-2-deoxy-
d
-glucose-enhanced positron emission tomography (2-
18
FFDG-PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) ...for the detection of bone marrow metastases in children and young adults with solid malignancies.
Methods
In this cross-sectional single-center institutional review board-approved study, we investigated twenty-three children and young adults (mean age, 16.8 years ± 5.1 standard deviation; age range, 7–25 years; 16 males, 7 females) with 925 bone marrow metastases who underwent 66 simultaneous 2-
18
FFDG-PET and DW-MRI scans including 23 baseline scans and 43 follow-up scans after chemotherapy between May 2015 and July 2020. Four reviewers evaluated all foci of bone marrow metastasis on 2-
18
FFDG-PET and DW-MRI to assess concordance and measured the tumor-to-bone marrow contrast. Results were assessed with a one-sample Wilcoxon test and generalized estimation equation. Bone marrow biopsies and follow-up imaging served as the standard of reference.
Results
The reviewers detected 884 (884/925, 95.5%) bone marrow metastases on 2-
18
FFDG-PET and 893 (893/925, 96.5%) bone marrow metastases on DW-MRI. We found different “blind spots” for 2-
18
FFDG-PET and MRI: 2-
18
FFDG-PET missed subcentimeter lesions while DW-MRI missed lesions in small bones. Sensitivity and specificity were 91.0% and 100% for
18
F-FDG-PET, 89.1% and 100.0% for DW-MRI, and 100.0% and 100.0% for combined modalities, respectively. The diagnostic accuracy of combined 2-
18
FFDG-PET/MRI (100.0%) was significantly higher compared to either 2-
18
FFDG-PET (96.9%,
p
< 0.001) or DW-MRI (96.3%,
p
< 0.001).
Conclusions
Both 2-
18
FFDG-PET and DW-MRI can miss bone marrow metastases. The combination of both imaging techniques detected significantly more lesions than either technique alone.
Key Points
•
DW-MRI and 2-
18
FFDG-PET have different strengths and limitations for the detection of bone marrow metastases in children and young adults with solid tumors.
• Both modalities can miss bone marrow metastases, although the “blind spot” of each modality is different.
• A combined PET/MR imaging approach will achieve maximum sensitivity and specificity for the detection of bone marrow metastases in children with solid tumors.
Among the generic drugs in short supply is mechlorethamine, part of a standard regimen for pediatric Hodgkin's lymphoma. The Pediatric Hodgkin Lymphoma Consortium has substituted cyclophosphamide, ...which is less effective and increases the risk of complications.
Over the past several years, patients and caregivers have faced an increasing number of drug shortages, predominantly of generic injectable agents. The reasons for these shortages are complex. Narrow profit margins for generic drugs have limited the incentive to produce them. Other reasons include the limited number of manufacturers, increased worldwide demand, shortages of raw materials, production problems, aging production plants, stockpiling, and long timelines for approval.
1
Patient care may suffer significantly as a result: alternative drugs must be prescribed, but the replacement may be less efficacious, more toxic, prohibitively expensive, or all of the above, and safety may be . . .
Survivors of childhood Hodgkin's lymphoma (HL) are at risk for second malignant neoplasms (SMNs). It is theorized that this risk may be attenuated in patients treated with lower doses of radiation. ...We report the first long-term outcomes of a cohort of pediatric survivors of HL treated with chemotherapy and low-dose radiation.
Pediatric patients with HL (n = 112) treated at Stanford from 1970 to 1990 on two combined modality treatment protocols were identified. Treatment included six cycles of chemotherapy with 15 to 25.5 Gy involved-field radiation with optional 10 Gy boosts to bulky sites. Follow-up through September 1, 2007, was obtained from retrospective chart review and patient questionnaires.
One hundred ten children completed HL therapy; median follow-up was 20.6 years. Eighteen patients developed one or more SMNs, including four leukemias, five thyroid carcinomas, six breast carcinomas, and four sarcomas. Cumulative incidence of first SMN was 17% (95% CI, 10.5 to 26.7) at 20 years after HL diagnosis. The standard incidence ratio for any SMN was 22.9 (95% CI, 14.2 to 35) with an absolute excess risk of 93.7 cases per 10,000 person-years. All four secondary leukemias were fatal. For those with second solid tumors, the mean (+/- SE) 5-year disease-free and overall survival were 76% +/- 12% and 85% +/- 10% with median follow-up 5 years from SMN diagnosis.
Despite treatment with low-dose radiation, children treated for HL remain at significant risk for SMN. Sarcomas, breast and thyroid carcinomas occurred with similar frequency and latency as found in studies of children with HL who received high-dose radiation.
Ewing's sarcoma, a highly malignant tumor of children, adolescents, and young adults, often responds to local excision plus a now-standard four-drug regimen of chemotherapy. This study shows that ...standard chemotherapy alternating with courses of ifosfamide plus etoposide significantly improves survival in patients with nonmetastatic disease at the time of diagnosis, but not in those with metastatic disease.
Ewing's sarcoma is a highly malignant tumor of bone that occurs in children, adolescents, and young adults. When treated with local control measures only (surgery or radiation therapy), the disease has an extremely high fatality rate.
1
The use of adjuvant chemotherapy, which began in the early 1970s, resulted in a marked improvement in the outcome. Since the first Intergroup Ewing's Sarcoma Study demonstrated improved outcomes with the inclusion of doxorubicin, nearly every chemotherapy protocol for Ewing's sarcoma has been based on four drugs: doxorubicin, cyclophosphamide, vincristine, and dactinomycin.
2
–
4
In the early 1980s, treatment with ifosfamide, with or without etoposide, . . .
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