A scoring system for AML patients aged 70 years or older,eligible for intensive chemotherapy: a study based on a large European data set using the DATAML,SAL, and PETHEMA registries

In a context of therapeutic revolution in older adults with AML, it is becoming increasingly important to select patients for the various treatment options by taking account of short-term efficacy and toxicity as well as long-term survival. Here, the data from three European registries for 1,199 AML patients aged 70 years or older treated with intensive chemotherapy were used to develop a prognostic scoring system. The median follow-up was 50.8 months. In the training set of 636 patients, age, performance status, secondary AML, leukocytosis, and cytogenetics, as well as NPM1 mutations (without FLT3-ITD), were all significantly associated with overall survival, albeit not to the same degree. These factors were used to develop a score that predicts long-term overall survival. Three risk-groups were identified: a lower, intermediate and higher-risk score with predicted 5-year overall survival (OS) probabilities of ≥12% (n = 283, 51%; median OS = 18 months), 3–12% (n = 226, 41%; median OS = 9 months) and <3% (n = 47, 8%; median OS = 3 months), respectively. This scoring system was also significantly associated with complete remission, early death and relapse-free survival; performed similarly in the external validation cohort (n = 563) and showed a lower false-positive rate than previously published scores. The European Scoring System ≥70, easy for routine calculation, predicts long-term survival in older AML patients considered for intensive chemotherapy.Subject terms: Acute myeloid leukaemia, Risk factors     

Walnut Oil Reduces Aβ Levels and Increases Neurite Length in a Cellular Model of Early Alzheimer Disease

(1) Background: Mitochondria are the cells’ main source of energy. Mitochondrial dysfunction represents a key hallmark of aging and is linked to the development of Alzheimer’s disease (AD). Maintaining mitochondrial function might contribute to healthy aging and the prevention of AD. The Mediterranean diet, including walnuts, seems to prevent age-related neurodegeneration. Walnuts are a rich source of α-linolenic acid (ALA), an essential n3-fatty acid and the precursor for n3-long-chain polyunsaturated fatty acids (n3-PUFA), which might potentially improve mitochondrial function. (2) Methods: We tested whether a lipophilic walnut extract (WE) affects mitochondrial function and other parameters in human SH-SY5Y cells transfected with the neuronal amyloid precursor protein (APP695). Walnut lipids were extracted using a Soxhlet Extraction System and analyzed using GC/MS and HPLC/FD. Adenosine triphosphate (ATP) concentrations were quantified under basal conditions in cell culture, as well as after rotenone-induced stress. Neurite outgrowth was investigated, as well as membrane integrity, cellular reactive oxygen species, cellular peroxidase activity, and citrate synthase activity. Beta-amyloid (Aβ) was quantified using homogenous time-resolved fluorescence. (3) Results: The main constituents of WE are linoleic acid, oleic acid, α-linolenic acid, and γ- and δ-tocopherol. Basal ATP levels following rotenone treatment, as well as citrate synthase activity, were increased after WE treatment. WE significantly increased cellular reactive oxygen species but lowered peroxidase activity. Membrane integrity was not affected. Furthermore, WE treatment reduced Aβ_1–40 and stimulated neurite growth. (4) Conclusions: WE might increase ATP production after induction of mitochondrial biogenesis. Decreased Aβ_1–40 formation and enhanced ATP levels might enhance neurite growth, making WE a potential agent to enhance neuronal function and to prevent the development of AD. In this sense, WE could be a promising agent for the prevention of AD.     

Impact of cardiovascular risk factors on vessel wall inflammation and calcified plaque burden differs across vascular beds: a PET-CT study

To evaluate the effect of age, gender and cardiovascular risk factors on vessel wall inflammation and the calcified plaque burden in different vascular beds as assessed by PET/CT. 315 patients (mean age: 57.8 years, 123 male and 192 female) who underwent whole body 18F-FDG PET/CT examinations were included in the study. Blood pool-corrected standardised uptake value (TBR) and the calcified plaque score (CPS, grade 0–4) were determined in the thoracic and abdominal aorta, both common carotid and both iliac arteries. The following cardiovascular risk factors were documented: Age ≥65 years (n = 114), male gender (n = 123), diabetes (n = 15), hyperlipidemia (n = 62), hypertension (n = 76), body mass index (BMI) ≥ 30 (n = 38), current smoker (n = 32). Effects of risk factors on TBR and CPS in different arterial beds were assessed using multivariate regression analysis. In the thoracic aorta TBR was independently associated with age ≥65 years and male gender, CPS was independently associated with age ≥65 years, male gender, hypertension and diabetes. In the abdominal aorta, TBR was independently associated with age ≥65 years and male gender, CPS with age ≥65 years, diabetes and smoking. Independent associations in the carotid arteries were found for age ≥65 years, male gender and BMI ≥ 30 in TBR and for age ≥65 and diabetes in CPS. In the iliac arteries, TBR was independently associated with age ≥65 and CPS with age ≥65, male gender, hypertension, diabetes and smoking. Findings of this PET/CT study demonstrate that the impact of cardiovascular risk factors on vessel wall inflammation and calcified plaque burden differs across vascular territories. Overall, CPS was more closely associated with cardiovascular risk factors compared to TBR.     

Use of limited color-flow duplex for a carotid screening project.

BACKGROUND: Although the efficacy of carotid endarterectomy for asymptomatic carotid stenosis has been established, no cost-effective approach for identification of these patients has yet been devised. The purpose of this study was to develop a limited carotid duplex screening examination to be utilized for the detection of asymptomatic carotid stenoses. METHODS: Carotid screening examinations employed rapid identification of the carotid bifurcation using color-flow duplex imaging and an immediate Doppler-derived velocity of the segment of the internal carotid artery with the most turbulent flow. Complete examinations were then finished using well-established protocols in our accredited vascular laboratory. A total of 512 patients were referred for complete studies based upon standard indications. Criteria for at least a 50% internal carotid artery stenosis on the complete examination was defined as a peak systolic velocity (PSV) of at least 125 cm/sec. Receiver operator characteristic (ROC) curves were then constructed to identify the optimal screening velocity criteria as compared with the final results on the complete examination. RESULTS: Five screening examinations were technically limited yielding a total of 507 patients with 1,014 carotid arteries available for analysis. Comparison of screening examinations versus complete examinations for a PSV of 125 cm/sec yielded sensitivity 86%, specificity 98%, positive predictive value (PPV) 95%, and a negative predictive value (NPV) 93%. ROC analysis identified a "cut point" of 115 cm/sec on the screening examinations to achieve sensitivity 91%, specificity 95%, PPV 89%, and NPV 96%. Time to perform screening examinations averaged 3.2 minutes per patient. Three patients had common carotid lesions not identified on the limited internal carotid screening examinations. CONCLUSIONS: Screening carotid examinations are a rapid, reliable, and relatively inexpensive method for detection of patients with asymptomatic internal carotid artery stenosis. Limited screening examinations should be developed in each vascular laboratory and utilized in high-risk patients.     

Validity of intra-operative neuromonitoring signals in thyroid surgery

Background Although intra-operative neuromonitoring (IONM) is widely used in thyroid surgery, the validity of the received IONM signals are still unknown.Method Prospective collection of data forms in 29 hospitals from 8,534 patients with 15,403 nerves at risk, who underwent surgery for benign and malignant goitre disorders between August 1999 and January 2001. IONM was performed by indirect stimulation via the vagal nerve and by direct recurrent laryngeal nerve (RLN) stimulation in 12,486 cases. IONM signals were compared with early (<14 days) and late (6 months) postoperative vocal cord function findings.Results The transient and permanent RLN palsy rate was 2.8% and 0.7%, respectively. Monitoring of the RLN function was significantly more reliable via the indirect IONM stimulation route than via the direct IONM stimulation route (specificity P<0.05). IONM by indirect stimulation via the vagal nerve reliably excluded postoperative, permanent, vocal cord palsy (specificity 97.6%, negative predictive value 99.6%). However, a changed IONM was insufficient to predict permanent RLN palsy (sensitivity 45.9%, positive predictive value 11.6%). IONM was not associated with increased general morbidity.Conclusions For intra-operative neuromonitoring, indirect stimulation of the RLN is superior to direct stimulation. An intact acoustic IONM signal is highly predictive of intact postoperative RLN function. When the IONM signal is abnormal or absent, a one-stage extensive thyroid resection should be performed only if the surgeon is absolutely convinced that the first RLN is not harmed or a total thyroidectomy is mandatory.     

Chondroblastoma of the acromion mimicking fibrous dysplasia

The authors report the case of a 65-year-old man who presented with an expansive osteolytic lesion in the right acromion, mimicking cystic fibrous dysplasia. Magnetic resonance imaging showed a lesion with intermediate-signal intensity on T1-weighted images and a high-signal intensity on fat suppressed T2-weighted images. The biopsy led to the diagnosis of chondroblastoma. This tumour is rare in flat bones, and may mimic other benign or malignant lesions. It is therefore essential to perform a biopsy in order to obtain a definite diagnosis. The acromion was excised, and replaced with an iliac crest graft.     

A GABAergic tecto–tegmento–tectal pathway in pigeons

Previous studies have demonstrated that the optic tecta of the left and right brain halves reciprocally inhibit each other in birds. In mammals, the superior colliculus receives inhibitory γ‐aminobutyric acid (GABA)ergic input from the basal ganglia via both the ipsilateral and the contralateral substantia nigra pars reticulata (SNr). This contralateral SNr projection is important in intertectal inhibition. Because the basal ganglia are evolutionarily conserved, the tectal projections of the SNr may show a similar pattern in birds. Therefore, the SNr could be a relay station in an indirect tecto–tectal pathway constituting the neuronal substrate for the tecto–tectal inhibition. To test this hypothesis, we performed bilateral anterograde and retrograde tectal tracing combined with GABA immunohistochemistry in pigeons. Suprisingly, the SNr has only ipsilateral projections to the optic tectum, and these are non‐GABAergic. Inhibitory GABAergic input to the contralateral optic tectum arises instead from a nearby tegmental region that receives input from the ipsilateral optic tectum. Thus, a disynaptic pathway exists that possibly constitutes the anatomical substrate for the inhibitory tecto–tectal interaction. This pathway likely plays an important role in attentional switches between the laterally placed eyes of birds. J. Comp. Neurol. 524:2886–2913, 2016. © 2016 Wiley Periodicals, Inc.     

Quantification of exhaled propofol is not feasible during single-lung ventilation using double-lumen tubes: A multicenter prospective observational trial

Background

Volatile propofol can be measured in exhaled air and correlates to plasma concentrations with a time delay. However, the effect of single-lung ventilation on exhaled propofol is unclear. Therefore, our goal was to evaluate exhaled propofol concentrations during single-lung compared to double-lung ventilation using double-lumen tubes.

Methods

In a first step, we quantified adhesion of volatile propofol to the inner surface of double-lumen tubes during double- and single-lumen ventilation in vitro. In a second step, we enrolled 30 patients scheduled for lung surgery in two study centers. Anesthesia was provided with propofol and remifentanil. We utilized left-sided double-lumen tubes to separately ventilate each lung. Exhaled propofol concentrations were measured at 1-min intervals and plasma for propofol analyses was sampled every 20 min. To eliminate the influence of dosing on volatile propofol concentration, exhalation rate was normalized to plasma concentration.

Results

In-vitro ventilation of double-lumen tubes resulted in increasing propofol concentrations at the distal end of the tube over time. In vitro clamping the bronchial lumen led to an even more pronounced increase (Δ AUC +62%) in propofol gas concentration over time. Normalized propofol exhalation during lung surgery was 31% higher during single-lung compared to double-lung ventilation.

Conclusion

During single-lung ventilation, propofol concentration in exhaled air, in contrast to our expectations, increased by approximately one third. However, this observation might not be affected by change in perfusion-ventilation during single-lung ventilation but rather arises from reduced propofol absorption on the inner surface area of the double-lumen tube. Thus, it is only possible to utilize exhaled propofol concentration to a limited extent during single-lung ventilation.

Registration of Clinical Trial

DRKS-ID DRKS00014788 ( www.drks.de ).