90 research outputs found
Denosumab in patients with aneurysmal bone systs: A case series with preliminary results
Abstract
PURPOSE::
Aneurysmal bone cyst (ABC) is a rare skeletal tumor usually treated with surgery/embolization. We hypothesized that owing to similarities with giant cell tumor of bone (GCTB), denosumab was active also in ABC.
METHODS::
In this observational study, a retrospective analysis of ABC patients treated with denosumab was performed. Patients underwent radiologic disease assessment every 3 months. Symptoms and adverse events were noted.
RESULTS::
Nine patients were identified (6 male, 3 female), with a median age of 17 years (range 14-42 years). Primary sites were 6 spine-pelvis, 1 ulna, 1 tibia, and 1 humerus. Patients were followed for a median time of 23 months (range 3-55 months). Patients received a median of 8 denosumab administrations (range 3-61). All symptomatic patients had pain relief and 1 had paresthesia improvement. Signs of denosumab activity were observed after 3 to 6 months of administration: bone formation by computed tomography scan was demonstrated in all patients and magnetic resonance imaging gadolinium contrast media decrease was observed in 7/9 patients. Adverse events were negligible. At last follow-up, all patients were progression-free: 5 still on denosumab treatment, 2 off denosumab were disease-free 11 and 17 months after surgery, and the last 2 patients reported no progression 12 and 24 months after denosumab interruption and no surgery.
CONCLUSIONS::
Denosumab has substantial activity in ABCs, with favorable toxicity profile. We strongly support the use of surgery and/or embolization for the treatment of ABC, but denosumab could have a role as a therapeutic option in patients with uncontrollable, locally destructive, or recurrent disease
Whole Lung Irradiation after High-Dose Busulfan/Melphalan in Ewing Sarcoma with Lung Metastases: An Italian Sarcoma Group and Associazione Italiana Ematologia Oncologia Pediatrica Joint Study
SIMPLE SUMMARY: The lung is the most frequent site of metastasis in Ewing sarcoma, the second most common bone cancer affecting children, adolescents and young adults. The five-year overall survival of patients with isolated lung metastasis is approximately 50% after multimodal treatments including chemotherapy, surgery and radiotherapy. This retrospective study aimed to investigate the feasibility and the predictors of survival in 68 Ewing sarcoma patients with lung metastases who received high-dose chemotherapy with busulfan and melphalan, followed by reduced dose whole-lung irradiation, as part of two prospective and consecutive treatment protocols. This combined treatment strategy is feasible and might contribute to the disease control in lung metastatic Ewing sarcoma with responsive disease. Furthermore, the results of this study provide support to explore the treatment stratification for lung metastatic Ewing sarcoma based on the histological response of the primary tumor. ABSTRACT: Purpose: To analyze toxicity and outcome predictors in Ewing sarcoma patients with lung metastases treated with busulfan and melphalan (BU-MEL) followed by whole-lung irradiation (WLI). Methods: This retrospective study included 68 lung metastatic Ewing Sarcoma patients who underwent WLI after BU-MEL with autologous stem cell transplantation, as part of two prospective and consecutive treatment protocols. WLI 12 Gy for <14 years old and 15 Gy for ≥14 years old patients were applied at least eight weeks after BU-MEL. Toxicity, overall survival (OS), event-free survival (EFS) and pulmonary relapse-free survival (PRFS) were estimated and analyzed. Results: After WLI, grade 1–2 and grade 3 clinical toxicity was reported in 16.2% and 5.9% patients, respectively. The five-year OS, EFS and PRFS with 95% confidence interval (CI) were 69.8% (57.1–79.3), 61.2% (48.4–71.7) and 70.5% (56.3–80.8), respectively. Patients with good histological necrosis of the primary tumor after neoadjuvant chemotherapy showed a significant decreased risk of pulmonary relapse or death compared to patients with poor histological necrosis. Conclusions: WLI at recommended doses and time interval after BU-MEL is feasible and might contribute to the disease control in Ewing sarcoma with lung metastases and responsive disease. Further studies are needed to explore the treatment stratification based on the histological response of the primary tumor
Prevalence of human papillomavirus and Helicobacter pylori in esophageal and gastroesophageal junction cancer biopsies from a case-control study in Ethiopia
peer reviewe
BRAF Activation Initiates but Does Not Maintain Invasive Prostate Adenocarcinoma
Prostate cancer is the second leading cause of cancer-related deaths in men. Activation of MAP kinase signaling pathway has been implicated in advanced and androgen-independent prostate cancers, although formal genetic proof has been lacking. In the course of modeling malignant melanoma in a tyrosinase promoter transgenic system, we developed a genetically-engineered mouse (GEM) model of invasive prostate cancers, whereby an activating mutation of BRAFV600E–a mutation found in ∼10% of human prostate tumors–was targeted to the epithelial compartment of the prostate gland on the background of Ink4a/Arf deficiency. These GEM mice developed prostate gland hyperplasia with progression to rapidly growing invasive adenocarcinoma without evidence of AKT activation, providing genetic proof that activation of MAP kinase signaling is sufficient to drive prostate tumorigenesis. Importantly, genetic extinction of BRAFV600E in established prostate tumors did not lead to tumor regression, indicating that while sufficient to initiate development of invasive prostate adenocarcinoma, BRAFV600E is not required for its maintenance
Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: A systematic analysis from the Global Burden of Disease Study 2016
Background A key component of achieving universal health coverage is ensuring that all populations have access to
quality health care. Examining where gains have occurred or progress has faltered across and within countries is
crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries,
and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access
and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from
1990 to 2016.
Methods Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which
death should not occur in the presence of effective care to approximate personal health-care access and quality by
location and over time. To better isolate potential effects of personal health-care access and quality from underlying
risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local
joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion
of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised
death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We
transformed each cause to a scale of 0–100, with 0 as the first percentile (worst) observed between 1990 and 2016, and
100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational
locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values,
providing an overall score of 0–100 of personal health-care access and quality by location over time. We then compared
HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall
development. As derived from the broader GBD study and other data sources, we examined relationships between
national HAQ Index scores and potential correlates of performance, such as total health spending per capita.
Findings In 2016, HAQ Index performance spanned from a high of 97·1 (95% UI 95·8–98·1) in Iceland, followed by
96·6 (94·9–97·9) in Norway and 96·1 (94·5–97·3) in the Netherlands, to values as low as 18·6 (13·1–24·4) in
the Central African Republic, 19·0 (14·3–23·7) in Somalia, and 23·4 (20·2–26·8) in Guinea-Bissau. The pace of
progress achieved between 1990 and 2016 varied, with markedly faster improvements occurring between 2000 and
2016 for many countries in sub-Saharan Africa and southeast Asia, whereas several countries in Latin America and
elsewhere saw progress stagnate after experiencing considerable advances in the HAQ Index between 1990 and 2000.
Striking subnational disparities emerged in personal health-care access and quality, with China and India having
particularly large gaps between locations with the highest and lowest scores in 2016. In China, performance ranged
from 91·5 (89·1–93·6) in Beijing to 48·0 (43·4–53·2) in Tibet (a 43·5-point difference), while India saw a 30·8-point
disparity, from 64·8 (59·6–68·8) in Goa to 34·0 (30·3–38·1) in Assam. Japan recorded the smallest range in
subnational HAQ performance in 2016 (a 4·8-point difference), whereas differences between subnational locations
with the highest and lowest HAQ Index values were more than two times as high for the USA and three times as high
for England. State-level gaps in the HAQ Index in Mexico somewhat narrowed from 1990 to 2016 (from a 20·9-point
to 17·0-point difference), whereas in Brazil, disparities slightly increased across states during this time (a 17·2-point
to 20·4-point difference). Performance on the HAQ Index showed strong linkages to overall development, with high
and high-middle SDI countries generally having higher scores and faster gains for non-communicable diseases.
Nonetheless, countries across the development spectrum saw substantial gains in some key health service areas from
2000 to 2016, most notably vaccine-preventable diseases. Overall, national performance on the HAQ Index was
positively associated with higher levels of total health spending per capita, as well as health systems inputs, but these
relationships were quite heterogeneous, particularly among low-to-middle SDI countries.
Interpretation GBD 2016 provides a more detailed understanding of past success and current challenges in improving
personal health-care access and quality worldwide. Despite substantial gains since 2000, many low-SDI and middle-
SDI countries face considerable challenges unless heightened policy action and investments focus on advancing access to and quality of health care across key health services, especially non-communicable diseases. Stagnating or
minimal improvements experienced by several low-middle to high-middle SDI countries could reflect the complexities
of re-orienting both primary and secondary health-care services beyond the more limited foci of the Millennium
Development Goals. Alongside initiatives to strengthen public health programmes, the pursuit of universal health
coverage hinges upon improving both access and quality worldwide, and thus requires adopting a more comprehensive
view—and subsequent provision—of quality health care for all populations.info:eu-repo/semantics/publishedVersio
Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy
IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical
attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced
colorectal cancers at diagnosis.
OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced
oncologic stage and change in clinical presentation for patients with colorectal cancer.
DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all
17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December
31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period),
in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was
30 days from surgery.
EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery,
palliative procedures, and atypical or segmental resections.
MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer
at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as
cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding,
lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery,
and palliative surgery. The independent association between the pandemic period and the outcomes
was assessed using multivariate random-effects logistic regression, with hospital as the cluster
variable.
RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years)
underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142
(56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was
significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR],
1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic
lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03).
CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the
SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients
undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for
these patients
Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016
As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016
Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016
BACKGROUND: Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI).
METHODS: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate.
FINDINGS: The highest globally observed HALE at birth for both women and men was in Singapore, at 75·2 years (95% uncertainty interval 71·9-78·6) for females and 72·0 years (68·8-75·1) for males. The lowest for females was in the Central African Republic (45·6 years [42·0-49·5]) and for males was in Lesotho (41·5 years [39·0-44·0]). From 1990 to 2016, global HALE increased by an average of 6·24 years (5·97-6·48) for both sexes combined. Global HALE increased by 6·04 years (5·74-6·27) for males and 6·49 years (6·08-6·77) for females, whereas HALE at age 65 years increased by 1·78 years (1·61-1·93) for males and 1·96 years (1·69-2·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2·3% [-5·9 to 0·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16·1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally.
INTERPRETATION: At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support.
FUNDING: Bill & Melinda Gates Foundation
Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.
The Global Burden of Diseases, Injuries and Risk Factors 2017 includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. METHODS: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting
Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016
The UN’s Sustainable Development Goals (SDGs) are grounded in the global ambition of “leaving no one behind”. Understanding today’s gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990–2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030
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