The results of salvage surgery combined with reirradiation in nodal recurrence of larynx cancer

The recurrence in the regional lymph nodes of patients after total laryngectomy and postoperative radiotherapy is a still serious therapeutic problem. The conditions that are altered following the combined primary treatment make it difficult to achieve satisfactory results of the second surgical treatment.The aim of our study was to evaluate the outcome of a salvage operation (lymphadenectomy) and reirradiation in 50 patients with recurrence in regional lymph nodes (rN). Beetwen 1991 and 1996, 650 patients with larynx carcinoma were treated in our institiutions. All patients during the primary irradiation received a total dose of about 60 Gy. In the case of regional recurrence (rN) patients had selective lymphadenectomy and reirradiation (total dose 40 Gy) when capsulae were found to be infiltrated. The survival rates were for 1, 2 and 3 years : 34 (68%), 22 (44%), only 9 (18%) respectivly. This strategy of a second combined treatment had a good tolerance level, without any unacceptable side effects (complications)

Multi vegetation model evaluation of the Green Sahara climate regime

During the Quaternary, the Sahara desert was periodically colonized by vegetation, likely because of orbitally induced rainfall increases. However, the estimated hydrological change is not reproduced in climate model simulations, undermining confidence in projections of future rainfall. We evaluated the relationship between the qualitative information on past vegetation coverage and climate for the mid-Holocene using three different dynamic vegetation models. Compared with two available vegetation reconstructions, the models require 500–800 mm of rainfall over 20°–25°N, which is significantly larger than inferred from pollen but largely in agreement with more recent leaf wax biomarker reconstructions. The magnitude of the response also suggests that required rainfall regime of the early to middle Holocene is far from being correctly represented in general circulation models. However, intermodel differences related to moisture stress parameterizations, biases in simulated present-day vegetation, and uncertainties about paleosoil distributions introduce uncertainties, and these are also relevant to Earth system model simulations of African humid periods

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

A three-year time series of mineral dust deposits on the West African margin: Sedimentological and geochemical signatures and implications for interpretation of marine paleo-dust records

International audienceMineral dust deposits in the Northeastern Tropical Atlantic Ocean (NETAO) are an important contribution for reconstructing paleoenvironments and paleoclimates of West Africa. However, the interpretation of the changes in the sedimentological and geochemical characteristics of the dust deposits recorded in the marine sediments from the NETAO remains incomplete. In order to improve our understanding of dust proxies, in particular its mineralogical and geochemical provenance tracers, present-day dust deposition has been monitored at Mbour (∼80 km south of Dakar) on the Senegalese margin. Here we report a multi-proxy investigation of a unique three-year continuous time series of mineral dust deposits collected at a weekly (or better) temporal resolution over the March 2006–March 2009 period. Mass deposition flux and mean modal grain size display marked but reverse seasonal features, with higher flux during the winter/spring seasons and coarser grain size mode in summer when flux is minimal, reflecting contrasting transport patterns throughout the year. Similarly, clay mineralogy, the illite/kaolinite ratio in particular, shows seasonal fluctuations, manifesting the latitudinal displacement of the contributing domains of provenance in response to the seasonal migration of the ITCZ position and the associated wind systems. Our three-year record also reveals the occurrence of major deposition events superimposed on the seasonal pattern, generally during the winter/spring dry seasons and most frequently during the month of March. Our study shows that these major events, which contribute a large fraction of the total annual deposition flux, all originate from the western Sahara–Sahel (a major area of emission in the region beside the Bodele Depression, stretching from the Mauritanian and Western Saharan coasts to the Hoggar Mountains). Combined with air mass tri-dimensional back-trajectories and satellite images, the mineralogical and Sr–Nd isotopic compositions of these large dust events enable us to identify several mineralogically and geochemically distinct provenance sectors within this vast western area. Unlike the background dust deposits, the 87Sr/86Sr and the εNd isotopic signatures of the major dry events closely match that of the NETAO Late Holocene sediments, supporting the hypothesis that these events account for most of the aeolian terrigenous supply reaching the ocean floor. Although this database needs to be expanded, our results already provide useful constraints for the interpretation of the dust proxies' variations in marine sedimentary archives off Mauritania/Senegal in terms of changes in wind regimes and aridity over West Africa

Monsoon-driven Saharan dust variability over the past 240,000 years

International audienceReconstructions of past Saharan dust deposition in marine sediments provide foundational records of North African climate over time scales of 10(3) to 10(6) years. Previous dust records show primarily glacial-interglacial variability in the Pleistocene, in contrast to other monsoon records showing strong precessional variability. Here, we present the first Saharan dust record spanning multiple glacial cycles obtained using Th-230 normalization, an improved method of calculating fluxes. Contrary to previous data, our record from the West African margin demonstrates high correlation with summer insolation and limited glacial-interglacial changes, indicating coherent variability in the African monsoon belt throughout the late Pleistocene. Our results demonstrate that low-latitude Saharan dust emissions do not vary synchronously with high-and mid-latitude dust emissions, and they call into question the use of existing Plio-Pleistocene dust records to investigate links between climate and hominid evolution

Monsoon-driven Saharan dust variability over the past 240,000 years.

Reconstructions of past Saharan dust deposition in marine sediments provide foundational records of North African climate over time scales of 103 to 106 years. Previous dust records show primarily glacial-interglacial variability in the Pleistocene, in contrast to other monsoon records showing strong precessional variability. Here, we present the first Saharan dust record spanning multiple glacial cycles obtained using 230Th normalization, an improved method of calculating fluxes. Contrary to previous data, our record from the West African margin demonstrates high correlation with summer insolation and limited glacial-interglacial changes, indicating coherent variability in the African monsoon belt throughout the late Pleistocene. Our results demonstrate that low-latitude Saharan dust emissions do not vary synchronously with high- and mid-latitude dust emissions, and they call into question the use of existing Plio-Pleistocene dust records to investigate links between climate and hominid evolution