The efficacy and safety of a novel combination of weekly paclitaxel and the epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab for the first-line treatment of recurrent and/or ...metastatic squamous cell carcinoma of the head and neck were investigated.
Patients received paclitaxel (80 mg/m2) and cetuximab (400/250 mg/m2), weekly, until disease progression or unacceptable toxicity. The primary end point was response rate.
Among 46 patients enrolled, the overall response rate was 54% 95% confidence interval (CI) 39% to 69%, with 10 (22%) complete responses and a disease control rate of 80%. Median progression-free and overall survival times were 4.2 (95% CI 2.9–5.5 months) and 8.1 months (95% CI 6.6–9.6 months), respectively. Common grade 3/4 adverse events were acne-like rash (24%), asthenia (17%) and neutropenia (13%). Prior chemotherapy and the development of acne-like rash were associated with tumor response but not survival. No association between tumor EGFR expression or EGFR gene copy number and response or survival was found.
The combination of cetuximab and weekly paclitaxel was active and well tolerated by these poor prognosis patients and may be an option for the treatment of medically unfit patients, particularly those for whom platinum is contraindicated.
Soil organic carbon stock (SOCS) assessments at a national level are essential in the climate change mitigation role. Our study provides the first assessment of the SOC stored in entire Spanish ...surface soils obtained from one sampling protocol within a regular sampling framework in a short edaphic time. In this study, we analysed topsoil samples (0–30cm) from 4401 locations. SOC, soil bulk density and stoniness were measured to estimate SOCS. The results showed that half the Spanish areas obtained a SOC value below 1%. There is inherently wide spatial variability in SOC contents in Spain with low SOC concentration levels located in southern areas. The lowest SOC levels were associated with agricultural soils. However, no statistically significant differences were found between forestlands and grasslands. The mean SOCS in the Spanish topsoil layer was 56.57MgCha−1 and the total stored in topsoil was 2.8 Pg C. We were surprised to find that our estimates were 40% lower than those known to date for Spain. The results herein highlight the potential land use change for SOC sequestration in Spanish soils. Certain changes in agricultural practises (conservation tillage) or converting some unproductive croplands into grasslands or forestlands can increase carbon sequestration in soils.
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•We model spatial variability in Spanish soil organic carbon•We analysed topsoil samples from 4401 locations within a regular sampling.•We use a simple geostatistical method to estimate SOCS.•Half Spanish area obtained a SOC value below 1%.•Our estimates were 40% lower than was known to date for Spain.
Concurrent chemoradiotherapy (CCRT) is the standard treatment for patients with unresectable, nonmetastatic locoregionally advanced squamous-cell carcinoma of the head and neck (LASCCHN). This ...randomized, open-label, phase III clinical trial compared the efficacy between standard CCRT and two different induction chemotherapy (ICT) regimens followed by CCRT.
Patients with untreated LASCCHN were randomly assigned to ICT (three cycles), with either docetaxel (Taxotere), cisplatin and 5-fluorouracil (TPF arm) or cisplatin and 5-fluorouracil (PF arm), followed by CCRT 7 weeks of radiotherapy (RT) with cisplatin 100 mg/m2 on days 1, 22 and 43; or 7 weeks of CCRT alone. The primary end points were progression-free survival (PFS) and time-to-treatment failure (TTF).
In the intention-to-treat (ITT) population (n = 439), the median PFS times were 14.6 (95% CI, 11.6–20.4), 14.3 (95% CI, 11.8–19.3) and 13.8 months (95% CI, 11.0–17.5) at TPF-CCRT, PF-CCRT and CCRT arms, respectively (log-rank P = 0.56). The median TTF were 7.9 (95% CI, 5.9–11.8), 7.9 (95% CI, 6.5–11.8) and 8.2 months (95% CI, 6.7–12.6) for TPF-CCRT, PF-CCRT and CCRT alone, respectively (log-rank P = 0.90). There were no statistically significant differences for overall survival (OS). Toxic effects from ICT-CCRT were manageable.
Overall, this trial failed to show any advantage of ICT-CCRT over CCRT alone in patients with unresectable LASCCHN (ClinicalTrials.gov number, NCT00261703).
Data on risk factors for etiologic subtypes of ischemic stroke are still scant. The aim of this study was to characterize stroke subtypes regarding risk factor profile, outcome, and current treatment ...strategies.
We analyzed data from 5017 patients with acute ischemic stroke (42.4% women, aged 65.9+/-14.1 years) who were enrolled in a large multicenter hospital-based stroke data bank. Standardized data assessment and stroke subtype classification were used by all centers.
Sex and age distribution, major risk factors and comorbidities, recurrent stroke, treatment strategies, and outcome were all unevenly distributed among stroke subtypes (P<0.001, respectively). Cardioembolism, the most frequent etiology of stroke (25.6%), was particularly common in the elderly (those aged >70 years) and associated with an adverse outcome, a low rate of early stroke recurrence, and frequent use of thrombolytic therapy and intravenous anticoagulation. Large-artery atherosclerosis (20.9%), the most common cause of stroke in middle-aged patients (those aged 45 to 70 years), showed the highest male preponderance, highest rate of early stroke recurrence, and highest prevalence of previous transient ischemic attack, current smoking, and daily alcohol consumption among all subtypes. The highest prevalence of hypertension, diabetes mellitus, hypercholesterolemia, and obesity was found in small-vessel disease (20.5%), which, in turn, was associated with the lowest stroke severity and mortality.
Our results foster the concept of ischemic stroke as a polyetiologic disease with marked differences between subtypes regarding risk factors and outcome. Therefore, studies involving risk factors of ischemic stroke should differentiate between etiologic stroke subtypes.
Forests are major components of the global carbon cycle, providing substantial feedback to atmospheric greenhouse gas concentrations. Our ability to understand and predict changes in the forest ...carbon cycle--particularly net primary productivity and carbon storage--increasingly relies on models that represent biological processes across several scales of biological organization, from tree leaves to forest stands. Yet, despite advances in our understanding of productivity at the scales of leaves and stands, no consensus exists about the nature of productivity at the scale of the individual tree, in part because we lack a broad empirical assessment of whether rates of absolute tree mass growth (and thus carbon accumulation) decrease, remain constant, or increase as trees increase in size and age. Here we present a global analysis of 403 tropical and temperate tree species, showing that for most species mass growth rate increases continuously with tree size. Thus, large, old trees do not act simply as senescent carbon reservoirs but actively fix large amounts of carbon compared to smaller trees; at the extreme, a single big tree can add the same amount of carbon to the forest within a year as is contained in an entire mid-sized tree. The apparent paradoxes of individual tree growth increasing with tree size despite declining leaf-level and stand-level productivity can be explained, respectively, by increases in a tree's total leaf area that outpace declines in productivity per unit of leaf area and, among other factors, age-related reductions in population density. Our results resolve conflicting assumptions about the nature of tree growth, inform efforts to undertand and model forest carbon dynamics, and have additional implications for theories of resource allocation and plant senescence.
Dendritic cells (DCs) are essential in antitumor immunity. In humans, three main DC subsets are defined: two types of conventional DCs (cDC1s and cDC2s) and plasmacytoid DCs (pDCs). To study DC ...subsets in the tumor microenvironment (TME), it is important to correctly identify them in tumor tissues. Tumor‐derived DCs are often analyzed in cell suspensions in which spatial information about DCs which can be important to determine their function within the TME is lost. Therefore, we developed the first standardized and optimized multiplex immunohistochemistry panel, simultaneously detecting cDC1s, cDC2s, and pDCs within their tissue context. We report on this panel's development, validation, and quantitative analysis. A multiplex immunohistochemistry panel consisting of CD1c, CD303, X‐C motif chemokine receptor 1, CD14, CD19, a tumor marker, and DAPI was established. The ImmuNet machine learning pipeline was trained for the detection of DC subsets. The performance of ImmuNet was compared with conventional cell phenotyping software. Ultimately, frequencies of DC subsets within several tumors were defined. In conclusion, this panel provides a method to study cDC1s, cDC2s, and pDCs in the spatial context of the TME, which supports unraveling their specific roles in antitumor immunity.
In this paper, we describe the development, validation, and quantitative analysis of a multiplex immunohistochemistry panel pipeline with which conventional type 1 dendritic cells (cDC1s), cDC2s, and plasmacytoid DCs can be detected in the spatial context of the tumor microenvironment.
Data regarding the association between folate status and risk of prostate cancer are sparse and conflicting. We studied prostate cancer occurrence in the Aspirin/Folate Polyp Prevention Study, a ...placebo-controlled randomized trial of aspirin and folic acid supplementation for the chemoprevention of colorectal adenomas conducted between July 6, 1994, and December 31, 2006. Participants were followed for up to 10.8 (median = 7.0, interquartile range = 6.0–7.8) years and asked periodically to report all illnesses and hospitalizations. Aspirin alone had no statistically significant effect on prostate cancer incidence, but there were marked differences according to folic acid treatment. Among the 643 men who were randomly assigned to placebo or supplementation with folic acid, the estimated probability of being diagnosed with prostate cancer over a 10-year period was 9.7% (95% confidence interval CI = 6.5% to 14.5%) in the folic acid group and 3.3% (95% CI = 1.7% to 6.4%) in the placebo group (age-adjusted hazard ratio = 2.63, 95% CI = 1.23 to 5.65, Wald test P = .01). In contrast, baseline dietary folate intake and plasma folate in nonmultivitamin users were inversely associated with risk of prostate cancer, although these associations did not attain statistical significance in adjusted analyses. These findings highlight the potential complex role of folate in prostate cancer and the possibly different effects of folic acid–containing supplements vs natural sources of folate.
•SAB patients with vertebral osteomyelitis showed a high treatment failure rate (48%).•Treatment failure was primarily due to death within three months.•Failure was equally attributable to S. aureus ...or underlying diseases.•Higher age, comorbidities, local abscess formation and neurological deficits proved as independent risk factors for treatment failure.
Staphylococcus aureus is the most common cause of pyogenic vertebral osteomyelitis (VO). Studies indicate that S. aureus VO results in poor outcome. We aimed to investigate risk factors for treatment failure in patients with Staphylococcus aureus bloodstream infection (SAB) and VO.
We conducted a post hoc-analysis of data from a German bi-center prospective SAB cohort (2006–2014). Patients were followed-up for one year. Primary outcome was treatment failure defined as relapse and/or death within one year.
A total of 1069 patients with SAB were analyzed, with 92 VO patients. In addition to antibiotic treatment, surgery was performed in 60/92 patients. Treatment failed in 44/92 patients (death, n = 42; relapse, n = 2). Multivariable analysis revealed higher age (HR 1.04 per year, 95%CI 1.01–1.07), Charlson comorbidity index (HR 1.20, 95%CI 1.06–1.36), presence of neurologic deficits (HR 2.53, 95%CI 1.15–5.53) and local abscess formation (HR 3.35, 95%CI 1.39–8.04) as independent risk factors for treatment failure. In contrast, surgery seemed to be associated with a favourable outcome (HR 0.45 (95%CI 0.20–0.997)).
SAB patients with VO exhibit a high treatment failure rate. Red flags are older age, comorbidities, neurologic deficits and local abscess formation. Whether these patients benefit from intensified treatment (e.g. radical surgery, prolongation of antibiotics) should be investigated further.
BACKGROUNDBesides the treatment of cardiovascular risk factors, the prevention and treatment of secondary complications is the main focus of outpatient poststroke care. The spectrum of noteworthy ...complications after a stroke changes during the course of the treatment and constitutes a specific challenge of outpatient poststroke care. OBJECTIVE AND METHODSThis article provides references to the importance, management, diagnosis and treatment of the wide spectrum of nonvascular complications after stroke in the context of outpatient stroke aftercare. RESULTSPoststroke depression (PSD), anxiety disorders and post-stroke fatigue are common complications after stroke, which require a timely diagnosis and treatment. Furthermore, the incidence of newly diagnosed dementia is 20% within the first 6 months after a stroke. Here too, therapeutic and preventive strategies especially in the early stage can delay the subsequent burden of the disease and the dependency on care. About half of every newly diagnosed epilepsy in patients older than 60 years is the result of a stroke. Falls and subsequent injuries are another important complication and a common reason for rehospitalization after a stroke. Although nearly 50% of patients suffer from chronic pain after a stroke this is often not sufficiently recognized. CONCLUSIONThe wide spectrum of secondary complications after a stroke constitutes a complex, sustained and multidisciplinary challenge, which requires a cross-sectoral interaction of various and numerous actors in outpatient poststroke care.
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