Enhancing chlamydospore production in Duddingtonia flagrans on solid substrate: The impact of mannitol and varied cultivation conditions.

Duddingtonia flagrans is a nematophagous fungus which has shown promising results as a non-chemical parasitic control tool. The fungus disrupts the parasite's life cycle by trapping larvae in the environment through the networks generated from chlamydospores, thus preventing the reinfection of animals. One barrier to the development of a commercial product using this tool is the need to increase chlamydospore production in the laboratory for its administration to livestock. The purpose of this study was to evaluate the addition of mannitol to an enriched culture medium and the effect of adverse cultivation conditions on chlamydospore production. D. flagrans was cultivated on Petri dishes with corn agar for 4 weeks at 27 °C and 70% relative humidity (RH). Four groups were then formed, all with Sabouraud agar as a base, to which different growth inducers were added: GSA (glucose Sabouraud agar), GSA-MI (glucose Sabouraud agar + meso inositol), GSA-E (enriched glucose Sabouraud agar), and AE-M (enriched agar + mannitol). After 4 weeks, chlamydospores were recovered by washing the surface of each plate with distilled water and then quantified. The medium that yielded the highest amount of chlamydospores was subjected to different cultivation conditions: NC (normal conditions): 70% RH and 27 °C, AC (adverse conditions) 1: 20% RH and 40 °C, CA2: 60% RH and 27 °C, and CA3: 55% RH and 24 °C. It was determined that mannitol increases chlamydospore production (65x106 chlamydospores/plate), and when reducing humidity by 10% under cultivation conditions it resulted in an approximately 10% increase in chlamydospore production compared to the control group. These results suggest that the addition of polyols, as well as its cultivation under certain environmental conditions, can improve chlamydospore production on a laboratory scale.

A worldwide maize panel revealed new genetic variation for cold tolerance.

KEY MESSAGE: A large association panel of 836 maize inbreds revealed a broader genetic diversity of cold tolerance, as predominantly favorable QTL with small effects were identified, indicating that genomic selection is the most promising option for breeding maize for cold tolerance. Maize (Zea mays L.) has limited cold tolerance, and breeding for cold tolerance is a noteworthy bottleneck for reaching the high potential of maize production in temperate areas. In this study, we evaluate a large panel of 836 maize inbred lines to detect genetic loci and candidate genes for cold tolerance at the germination and seedling stages. Genetic variation for cold tolerance was larger than in previous reports with moderately high heritability for most traits. We identified 187 significant single-nucleotide polymorphisms (SNPs) that were integrated into 159 quantitative trait loci (QTL) for emergence and traits related to early growth. Most of the QTL have small effects and are specific for each environment, with the majority found under control conditions. Favorable alleles are more frequent in 120 inbreds including all germplasm groups, but mainly from Minnesota and Spain. Therefore, there is a large, potentially novel, genetic variability in the germplasm groups represented by these inbred lines. Most of the candidate genes are involved in metabolic processes and intracellular membrane-bounded organelles. We expect that further evaluations of germplasm with broader genetic diversity could identify additional favorable alleles for cold tolerance. However, it is not likely that further studies will find favorable alleles with large effects for improving cold tolerance in maize.

Effect of macrocyclic lactones on nontarget coprophilic organisms: a review.

Macrocyclic lactones are frequently used dewormers in livestock farms around the world. Due to their wide spectrum of action against nematodes and arthropods and their practicality of application at very low doses, their use has become massive since their discovery. These compounds are eliminated in a large percentage in the feces of animals, causing adverse effects on coprophilic fauna. Several research groups around the world have been devoted to evaluating these effects on this fauna. The aim of this review is to register the adverse effects of the concentrations in which macrocyclic lactones are eliminated in the feces of domestic animals and the importance of the coprophilic and edaphilous fauna on the degradation of the feces of the animals. The documented data shows that the use of macrocyclic lactones has a high toxicological risk for the different species that colonize the dung, thus causing an adverse effect on its disintegration and its subsequent incorporation into the soil. Even so, more studies at the regional level and their standardization are necessary to make the comparison between different areas possible.

Developing a Training Web Application for Improving the COVID-19 Diagnostic Accuracy on Chest X-ray.

In December 2019, a new coronavirus known as 2019-nCoV emerged in Wuhan, China. The virus has spread globally and the infection was declared pandemic in March 2020. Although most cases of coronavirus disease 2019 (COVID-19) are mild, some of them rapidly develop acute respiratory distress syndrome. In the clinical management, chest X-rays (CXR) are essential, but the evaluation of COVID-19 CXR could be a challenge. In this context, we developed COVID-19 TRAINING, a free Web application for training on the evaluation of COVID-19 CXR. The application included 196 CXR belonging to three categories: non-pathological, pathological compatible with COVID-19, and pathological non-compatible with COVID-19. On the training screen, images were shown to the users and they chose a diagnosis among those three possibilities. At any time, users could finish the training session and be evaluated through the estimation of their diagnostic accuracy values: sensitivity, specificity, predictive values, and global accuracy. Images were hand-labeled by four thoracic radiologists. Average values for sensitivity, specificity, and global accuracy were .72, .64, and .68. Users who achieved better sensitivity registered less specificity (p < .0001) and those with higher specificity decreased their sensitivity (p < .0001). Users who sent more answers achieved better accuracy (p = .0002). The application COVID-19 TRAINING provides a revolutionary tool to learn the necessary skills to evaluate COVID-19 on CXR. Diagnosis training applications could provide a new original manner of evaluation for medical professionals based on their diagnostic accuracy values, and an efficient method to collect valuable data for research purposes.

Dissecting the genetics of cold tolerance in a multiparental maize population.

KEY MESSAGE: We identify the largest amount of QTLs for cold tolerance in maize; mainly associated with photosynthetic efficiency, which opens new possibilities for genomic selection for cold tolerance in maize. Breeding for cold tolerance in maize is an important objective in temperate areas. The objective was to carry out a highly efficient study of quantitative trait loci (QTLs) for cold tolerance in maize. We evaluated 406 recombinant inbred lines from a multi-parent advanced generation intercross (MAGIC) population in a growth chamber under cold and control conditions, and in the field at early and normal sowing. We recorded cold tolerance-related traits, including the number of days from sowing to emergence, chlorophyll content and maximum quantum efficiency of photosystem II (Fv/Fm). Association mapping was based on genotyping with near one million single nucleotide polymorphism (SNP) markers. We found 858 SNPs significantly associated with all traits, most of them under cold conditions and early sowing. Most QTLs were associated with chlorophyll and Fv/Fm. Many candidate genes coincided between the current research and previous reports. These results suggest that (1) the MAGIC population is an efficient tool for identifying QTLs for cold tolerance; (2) most QTLs for cold tolerance were associated with Fv/Fm; (3) most of these QTLs were located in specific genomic regions, particularly bin 10.04; (4) the current study allows genetically improving cold tolerance with genome-wide selection.

Lack of negative effects of the biological control agent Duddingtonia flagrans on soil nematodes and other nematophagous fungi.

The possible environmental effects of the massive use of Duddingtonia flagrans for controlling sheep nematodes were evaluated in two regions. Non-supplemented faeces and faeces from sheep supplemented with D. flagrans were deposited three times on pasture plots and samples were collected 7 and 14 days post-deposition. Samples were cultured in agar-water (2%) with Panagrellus spp. to recover D. flagrans and other nematophagous fungi, and soil nematodes were extracted using Baermann funnels and counted. No significant differences in the populations of soil nematodes and fungi colonizing sheep faeces (P > 0.05) were observed between supplemented and non-supplemented groups, except in one sample. The topsoil in contact with the faeces was sampled 1-4 months post-deposition, revealing that, with one exception, D. flagrans did not persist in soil beyond 2 months post-deposition. Duddingtonia flagrans does not affect faecal colonization by other fungi and soil nematodes and, once deployed on pasture, does not survive for long periods in the environment.

Cisplatin, 5-fluorouracil, and cetuximab (PFE) with or without cilengitide in recurrent/metastatic squamous cell carcinoma of the head and neck: results of the randomized phase I/II ADVANTAGE trial (phase II part).

BACKGROUND: Recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN) overexpresses αvß5 integrin. Cilengitide selectively inhibits αvß3 and αvß5 integrins and is investigated as a treatment strategy. PATIENTS AND METHODS: The phase I/II study ADVANTAGE evaluated cilengitide combined with cisplatin, 5-fluorouracil, and cetuximab (PFE) in R/M-SCCHN. The phase II part reported here was an open-label, randomized, controlled trial investigating progression-free survival (PFS). Patients received up to six cycles of PFE alone or combined with cilengitide 2000 mg once (CIL1W) or twice (CIL2W) weekly. Thereafter, patients received maintenance therapy (cilengitide arms: cilengitide plus cetuximab; PFE-alone arm: cetuximab only) until disease progression or unacceptable toxicity. RESULTS: One hundred and eighty-two patients were treated. Median PFS per investigator read was similar for CIL1W + PFE, CIL2W + PFE, and PFE alone (6.4, 5.6, and 5.7 months, respectively). Accordingly, median overall survival and objective response rates were not improved with cilengitide (12.4 months/47%, 10.6 months/27%, and 11.6 months/36%, respectively). No clinically meaningful safety differences were observed between groups. None of the tested biomarkers (expression of integrins, CD31, Ki-67, vascular endothelial growth factor receptor 2, vascular endothelial-cadherin, type IV collagen, epidermal growth factor receptor, or p16 for human papillomavirus) were predictive of outcome. CONCLUSION: Neither of the cilengitide-containing regimens demonstrated a PFS benefit over PFE alone in R/M-SCCHN patients.

The use of soy protein polymers as a release device for nematophagous fungi in the control of parasitic nematodes in ruminants.

This trial was conducted to evaluate the predatory activity of Duddingtonia flagrans incorporated into soy protein-based polymers as a controlled-release device (CRD). The rate of fungal release from the polymers and time of residence of the CRD in the rumen of a cannulated sheep was also determined. After administration to the sheep, the CRD was extracted at weekly intervals over a month for observation of its physical structure and faeces were collected to observe the subsequent predatory activity of the fungus in Petri dishes with water-agar 2% and Panagrellus spp. as bait. The CRD slowly degraded in the rumen over 4 weeks and liberated D. flagrans into the faeces. The formulation of the soy protein-based polymers did not affect the predatory activity of the fungus. The study demonstrates that biodegradable soy protein polymers could potentially improve the use of nematophagous fungi for controlling nematode parasites of ruminants.

Documento de consenso sobre tabaquismo y riesgo vascular.

Consensus statement on smoking and vascular risk About 22% of the Spanish population are daily smokers. Men are more likely to smoke than women. In Spain, women between 15-25 years of age smoke as much or more than men. Every smoker should be assessed for: physical dependence on nicotine (Fagerström test), social and psychological dependence (Glover Nilsson test), level of motivation to quit (Richmond test), probability of therapy success (Henri-Mondor and Michael-Fiore tests), and stage of behavioral change development (Prochaska and DiClementi). Advice on smoking cessation is highly cost-effective and should always be provided. Smoking is an enhancer of cardiovascular risk because it acts as a pathogen agent in the development of arteriosclerosis and is associated with ischemic heart disease, stroke, and peripheral artery disease. Smoking increases the risk of chronic lung diseases (COPD) and is related to cancers of the lung, female genitalia, larynx, oropharynx, bladder, mouth, esophagus, liver and biliary tract, and stomach, among others. Combined oral contraceptives should be avoided in women smokers older than 35 years of age due to the risk of thromboembolism. In smoking cessation, the involvement of physicians, nurses, psychologists, etc. is important, and their multidisciplinary collaboration is needed. Effective pharmacological treatments for smoking cessation are available. Combined treatments are recommended when smoker's dependence is high. For individuals who are unable to quit smoking, a strategy based on tobacco damage management with a total switch to smokeless products could be a less dangerous alternative for their health than continuing to smoke.

A rational approach to the regioselective deacetylation of 2',3',5'-tri-O-acetyluridine by Novozym 435 catalysed alcoholysis.

To give a rational explanation for the behaviour of 2',3',5'-tri-O-acetyluridine (TAU) catalysed alcoholysis using Novozym 435, the commercial biocatalyst with immobilized Candida antarctica lipase B (CALB), a set of experiments analyzing the role of the alcohol/substrate (A/S) molar ratio, alcohol/biocatalyst (A/B) and substrate/biocatalyst (S/B) mass ratios were carried out. At a A/S=120 and a S/B=6.16, 2',3'-di-O-acetyluridine (DAU) was obtained in 92% at 22h. The observed trend towards the exclusive formation of DAU at very high alcohol amounts can be explained on the basis of the change of substrate orientation from normal to inverse. The simple molecular modelling analysis supports that key O/H atoms from TAU and the resulting intermediates display the adequate distances to generate productive binding only when the inverse coordination of TAU is present through the 5'-moiety of TAU, at high ethanol concentrations. At these conditions a possible allosteric-like effect of ethanol, combined with water in an H-network in the catalytic triad and in its neighbourhood, could explain the high selectivity towards the production of DAU at selected conditions.

Invasive device-related infections after heart surgery.

OBJECTIVE: To analyze postoperative infections in critically ill patients undergoing heart surgery. SETTING: Intensive care units (ICUs). DESIGN: An observational, prospective, multicenter study was carried out. PATIENTS: Patients in the postoperative period of heart surgery admitted to the ICU and included in the ENVIN-HELICS registry between 2005 and 2011. MAIN OUTCOME VARIABLES: Mechanical ventilation associated pneumonia (MVP), urinary catheter-related infection (UCI), primary bacteremia (PB), PB related to vascular catheters (PB-VC) and secondary bacteremia. RESULTS: Of a total of 97,692 patients included in the study, 9089 (9.3%) had undergone heart surgery. In 440 patients (4.8%), one or more infections were recorded. Infection rates were 9.94 episodes of MVP per 1000 days of mechanical ventilation, 3.4 episodes of UCI per 1000 days of urinary catheterization, 3.10 episodes of BP-VC per 1000 days of central venous catheter, and 1.84 episodes of secondary bacteremia per 1000 days of ICU stay. Statistically significant risk factors for infection were ICU stay (odds ratio [OR] 1.18, 95%CI 1.16-1.20), APACHE II upon admission to the ICU (OR 1.05, 95%CI 1.03-1.07), emergency surgery (OR 1.67, 95%CI 1.13-2.47), previous antibiotic treatment (OR 1.38, 95%CI 1.04-1.83), and previous colonization by Pseudomonas aeruginosa (OR 18.25, 95%CI 3.74-89.06) or extended spectrum beta-lactamase producing enterobacteria (OR 16.97, 95%CI 5.4-53.2). The overall ICU mortality rate was 4.1% (32.2% in patients who developed one or more infections and 2.9% in uninfected patients) (P < .001). CONCLUSIONS: Of the patients included in the ENVIN-HELICS registry, 9.3% were postoperative heart surgery patients. The overall mortality was low but increased significantly in patients who developed one or more infection episodes.

Energetic Electron Precipitation Driven by Electromagnetic Ion Cyclotron Waves from ELFIN's Low Altitude Perspective.

We review comprehensive observations of electromagnetic ion cyclotron (EMIC) wave-driven energetic electron precipitation using data collected by the energetic electron detector on the Electron Losses and Fields InvestigatioN (ELFIN) mission, two polar-orbiting low-altitude spinning CubeSats, measuring 50-5000 keV electrons with good pitch-angle and energy resolution. EMIC wave-driven precipitation exhibits a distinct signature in energy-spectrograms of the precipitating-to-trapped flux ratio: peaks at >0.5 MeV which are abrupt (bursty) (lasting ∼17 s, or ΔL∼0.56) with significant substructure (occasionally down to sub-second timescale). We attribute the bursty nature of the precipitation to the spatial extent and structuredness of the wave field at the equator. Multiple ELFIN passes over the same MLT sector allow us to study the spatial and temporal evolution of the EMIC wave - electron interaction region. Case studies employing conjugate ground-based or equatorial observations of the EMIC waves reveal that the energy of moderate and strong precipitation at ELFIN approximately agrees with theoretical expectations for cyclotron resonant interactions in a cold plasma. Using multiple years of ELFIN data uniformly distributed in local time, we assemble a statistical database of ∼50 events of strong EMIC wave-driven precipitation. Most reside at L∼5-7 at dusk, while a smaller subset exists at L∼8-12 at post-midnight. The energies of the peak-precipitation ratio and of the half-peak precipitation ratio (our proxy for the minimum resonance energy) exhibit an L-shell dependence in good agreement with theoretical estimates based on prior statistical observations of EMIC wave power spectra. The precipitation ratio's spectral shape for the most intense events has an exponential falloff away from the peak (i.e., on either side of ∼1.45 MeV). It too agrees well with quasi-linear diffusion theory based on prior statistics of wave spectra. It should be noted though that this diffusive treatment likely includes effects from nonlinear resonant interactions (especially at high energies) and nonresonant effects from sharp wave packet edges (at low energies). Sub-MeV electron precipitation observed concurrently with strong EMIC wave-driven >1 MeV precipitation has a spectral shape that is consistent with efficient pitch-angle scattering down to ∼ 200-300 keV by much less intense higher frequency EMIC waves at dusk (where such waves are most frequent). At ∼100 keV, whistler-mode chorus may be implicated in concurrent precipitation. These results confirm the critical role of EMIC waves in driving relativistic electron losses. Nonlinear effects may abound and require further investigation.

Calprotectin: a novel biomarker for the diagnosis of pleural effusion.

BACKGROUND: Novel non-invasive biomarkers for the precise diagnosis of malignancy in pleural effusion (PE) are needed. The aim of this study was to determine the diagnostic accuracy of calprotectin for predicting malignancy in patients with exudative PE. METHODS: Calprotectin concentration was measured in 156 individuals diagnosed with exudative PE (67 malignant and 89 benign). Calprotectin accuracy for discriminating between malignant and benign PE was evaluated using receiver operating characteristic (ROC) curves. Univariate and multivariate logistic regression were performed to test the association between calprotectin levels and malignant PE. RESULTS: Calprotectin levels were significantly lower in malignant pleural fluid (257.2 ng ml(-1), range: 90.7-736.4) than benign effusions (2627.1 ng ml(-1), range: 21-9530.1). The area under the curve was 0.963. A cutoff point of ≤ 736.4 ng ml(-1) rendered a sensitivity of 100%, with a specificity of 83.15%, which could prove useful to delimit those patients with negative cytology tests that should be referred for more invasive diagnostic procedures. Logistic regression demonstrated a strong association between calprotectin and malignancy (adjusted OR 663.14). CONCLUSION: Calprotectin predicts malignancy in pleural fluid with high accuracy and could be a good complement to cytological methods.

Artificial Intelligence in Radiology: an introduction to the most important concepts.

The interpretation of medical imaging tests is one of the main tasks that radiologists do. For years, it has been a challenge to teach computers to do this kind of cognitive task; the main objective of the field of computer vision is to overcome this challenge. Thanks to technological advances, we are now closer than ever to achieving this goal, and radiologists need to become involved in this effort to guarantee that the patient remains at the center of medical practice. This article clearly explains the most important theoretical concepts in this area and the main problems or challenges at the present time; moreover, it provides practical information about the development of an artificial intelligence project in a radiology department.

[Morning blood pressure surge in patients with recent ischaemic stroke: the neglected factor]. / Incremento matutino de la presión arterial en pacientes con ictus isquémico reciente: el factor olvidado.

INTRODUCTION: High morning BP surge (MBPS) has been associated with an increased risk of cardiovascular events. We evaluated the presence of a high MBPS in patients with recent ischaemic stroke. MATERIAL AND METHODS: A case-control study was carried out. One hundred patients with an ischaemic stroke in the previous 6 months and fifty hypertensive patients without cardiovascular disease were included as controls. RESULTS: 61 lacunar (LAC) and 39 non-lacunar (NLAC) strokes were studied. The mean age was 65±11 years, and 60 (40%) patients were women. High MBPS was present in 9% of strokes (in 5 LAC and 4 NLAC) and in 8% of controls (p not significant [NS]), with a similar mean value of MBPS in both groups: 23.9±14mmHg and 24.9±15mmHg respectively (p=NS), although the control patients had a higher office BP (systolic [p=.008] and diastolic [p=.0001]), 24h systolic BP (p=.028) and daytime systolic BP (p=.022). Among the stroke patients, high MBPS was associated with previous coronary heart disease (p=.005), circadian BP pattern (p=.029), but not with the type of antihypertensive treatment prescribed. In multivariate analysis, elevated MBPS was only associated with previous coronary artery disease (p=.001). CONCLUSIONS: Approximately one in ten patients with recent ischaemic stroke has a high MBPS. Strategies to detect and treat high MBPS after a stroke are needed.

Broad bandwidth air-coupled micromachined ultrasonic transducers for gas sensing.

The present work aims to develop ultra-wide bandwidth air-coupled capacitive micromachined ultrasonic transducers (CMUTs) for binary gas mixture analysis. The detection principle is based on time-of-flight (ToF) measurements, in order to monitor gas ultrasound velocity variations. To perform such measurements, CMUTs were especially designed to work out of resonance mode, like a microphone. The chosen membrane size is 32 × 32 µm2 and gap height is 250 nm. The resonance frequency and collapse voltage were found at 8 MHz and 58 V respectively. As mentioned, the CMUTs were exploited in quasi-static operating mode, in a very low frequency band, from 1 MHz to 1.5 MHz frequencies. The transducer impulse response was characterised, and a -6 dB relative fractional frequency bandwidth (FBW) higher than 100% was measured, enabling to use CMUT for the targeted application. Additionally, a measuring cell has been designed to hold the fabricated CMUT emitter and receiver prototypes facing each other. The volume inside the cell was kept lower than 3 mL and the surface of emitter/receiver was 1.6 × 8 mm2. To validate the general principle of the proposed technique, two binary gas mixtures of CO2/N2 and H2/N2, with varying concentrations, have been tested. The results are very promising with a measured limit of detection (LOD) of 0.3% for CO2 in N2 and 0.15% for H2 in N2.

SEOM clinical guidelines for the treatment of head and neck cancer (2020).

Head and neck cancers (HNC) are defined as malignant tumours located in the upper aerodigestive tract and represents 5% of oncologic cases in adults in Spain. More than 90% of these tumours have squamous histology. In an effort to incorporate evidence obtained since 2017 publication, the Spanish Society of Medical Oncology (SEOM) presents an update of the squamous cell HNC diagnosis and treatment guideline. Most relevant diagnostic and therapeutic changes from the last guideline have been updated: introduction of sentinel node biopsy in early oral/oropharyngeal cancer treated with surgery, concomitant radiotherapy with weekly cisplatin 40 mg/m2 in the adjuvant setting, new approaches for HPV-related oropharyngeal cancer and new treatments with immune-checkpoint inhibitors in recurrent/metastatic disease.

Long-term outcomes of induction chemotherapy followed by chemoradiotherapy vs chemoradiotherapy alone as treatment of unresectable head and neck cancer: follow-up of the Spanish Head and Neck Cancer Group (TTCC) 2503 Trial.

BACKGROUND: Our previous phase-3 study (TTCC 2503) failed to show overall survival advantage of 2 induction chemotherapy (IC) regimens followed by standard concurrent chemoradiotherapy (CRT) over CRT alone in patients with unresectable locally advanced head and neck squamous-cell carcinoma (LAHNSCC). This study described the long-term survival of those patients. MATERIALS AND METHODS: Long-term follow-up study of patients with untreated LAHNSCC assigned to IC (three cycles), with either docetaxel, cisplatin and 5-fluorouracil (TPF arm) or cisplatin and 5-fluorouracil (PF arm), followed by CRT, or CRT alone, included in the previous TTCC 2503 trial. RESULTS: In the intention-to-treat population (n = 439), the median OS times were 25.4 (95% CI, 16.8-34.4), 26.2 (95% CI, 18.2-36.6) and 25.4 months (95% CI, 17.4-36.0) in the TPF-CRT, PF-CRT and CRT arms, respectively (log-rank p = 0.51). In the per-protocol population (n = 355), patients with larynx-hypopharynx primary tumors treated with IC (TPF or PF) followed by CRT had a longer median PFS than those who received CRT alone. Moreover, patients with ECOG 0 treated with IC (TPF or PF) followed by CRT had a better TTF than those with CRT alone. There were no statistically significant differences in terms of OS, PFS or TTF, according to the tumor load or affected nodes. CONCLUSION: After a long follow-up, the TTCC 2503 trial failed to show the benefit of IC-CRT in unresectable LAHNSCC regarding the primary end point. However, fit patients with ECOG 0 and primary larynx-hypopharyngeal tumors may benefit from the use of IC if administered by an experienced team. ClinicalTrials.gov identifier NCT00261703.

Extended-schedule dose-dense temozolomide in refractory gliomas.

This multicenter phase II study conducted by the Spanish Neuro-Oncology Group evaluated the activity of an extended, dose-dense temozolomide regimen in patients with temozolomide-refractory malignant glioma. Adult patients (at least 18 years of age) with WHO grade III or IV glioma and a Karnofsky Performance Status of 60 or higher were treated with temozolomide (85 mg/m(2)/day) for 21 consecutive days every 28-day cycle until disease progression or unacceptable toxicity. All patients had developed progressive disease either during or less than 3 months after completing previous temozolomide treatment. Forty-seven patients were treated with a median of 2 (range, 1-13) cycles of temozolomide. Before study entry, patients had received a median of 6 cycles of temozolomide: 39 (83%) as part of initial therapy and 23 (49%) as second-line therapy. Three patients (6.4%) had a partial response with durations of 8.0, 3.5, and 3.2 months; 15 patients (31.9%) had stable disease with a median duration of 2.1 months, including 2 patients with stable disease (SD) for greater than 6 months (14 and 16 months). Median time to progression was 2 months, and median overall survival from study entry was 5.1 months. The 6-month progression-free survival rate was 16.7%. The most common hematologic toxicities were lymphopenia, thrombocytopenia, and leukopenia. Lymphopenia occurred in 83% of patients and was grade 3 in 28%, but no opportunistic infections occurred. In conclusion, this extended dose-dense schedule of temozolomide appears to have modest activity in patients refractory to previous treatment with temozolomide and is associated with manageable toxicity.

SEOM clinical guideline thyroid cancer (2019).

Thyroid carcinoma is the most frequent endocrine malignancy and accounts for around 3% of global cancer incidence. Different histologies and clinical scenarios make necessary a multidisciplinary approach that includes new diagnostic methods and surgical, radiopharmaceutical and systemic therapies. This guideline updates several aspects of management of thyroid cancer.