Exploring management and outcomes of elderly patients with glioblastoma using data from two randomised trials (GEINO1401/EX-TEM).

PURPOSE: The impact of age on optimal management of glioblastoma remains unclear. A recent combined analysis of two randomised trials, GEINO14-01 and EX-TEM, found no benefit from extending post-radiation temozolomide in newly diagnosed glioblastoma. Here, we explore the impact of age. METHODS: Relevant intergroup statistics were used to identify differences in tumour, treatment and outcome characteristics based on age with elderly patients (EP) defined as age 65 years and over. Survival was estimated using the Kaplan Meier method. RESULTS: Of the combined 205 patients, 57 (28%) were EP. Of these, 95% were ECOG 0-1 and 65% underwent macroscopic resection compared with 97% and 61% of younger patients (YP) respectively. There were numerically less MGMT-methylated (56% vs. 63%, p = 0.4) and IDH-mutated (4% vs. 13%, p = 0.1) tumours in EP vs. YP. Following surgery, EP were more likely to receive short course chemoradiation (17.5% vs. 6%, p = 0.017). At recurrence, EP tended to receive or best supportive care (28.3% vs. 15.4%, p = 0.09) or non-surgical options (96.2% vs. 84.6%, p = 0.06), but were less likely to receive bevacizumab (23.1% vs. 49.5%, p < 0.01). Median PFS was similar at 9.3months in EP and 8.5months in YP, with similar median OS at 20months. CONCLUSION: In this trial population of predominantly fit EP, survival was similar to YP despite a proportion receiving less aggressive therapy at diagnosis and recurrence. Advancing age does not appear to be an adverse prognostic factor for glioblastoma when patients are fit for treatment, and a less aggressive approach in selected patients may not compromise outcomes.

A combined analysis of two prospective randomised studies exploring the impact of extended post-radiation temozolomide on survival outcomes in newly diagnosed glioblastoma.

PURPOSE: The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data. METHODS: GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6 months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60% (80% power). Neither study recruited sufficient patients. We performed a combined analysis of individual patient data. RESULTS: 205 patients were recruited: 159 in GEINO14-01 (2014-2018) and 46 in EX-TEM (2019-2022). Median follow-up was 20.0 and 14.5 months. Baseline characteristics were balanced. There was no significant improvement in 6mPFS (57.2% vs 64.0%, OR0.75, p = 0.4), nor across any subgroups, including MGMT methylated; PFS (HR0.92, p = 0.59, median 7.8 vs 9.7 months); or OS (HR1.03, p = 0.87, median 20.1 vs 19.4 months). During treatment extension, 64% experienced any grade adverse event, mainly fatigue and gastrointestinal (both 54%). Only a minority required treatment changes: 4.5% dose delay, 7.5% dose reduction, 1.5% temozolomide discontinuation. CONCLUSION: For glioblastoma patients, extending post-radiation temozolomide from 6 to 12 months is well tolerated but does not improve 6mPFS. We could not identify any subset that benefitted from extended treatment. Six months should remain standard-of-care.

La disfagia en cuidados intensivos, un problema real: análisis de factores de riesgo / Dysphagia in intensive care, a real problem: analysis of risk factors

Objetivos: Determinar los factores de riesgo presentes en los pacientes con disfagia en relación con una población de pacientes críticos. Método: Serie de casos de una cohorte de pacientes reclutados en la unidad de cuidados intensivos (UCI) hasta el alta hospitalaria. Se reclutaron a aquellos pacientes que dieron su consentimiento y cumplían los criterios de inclusión. El método de exploración clínica Volumen-Viscosidad fue utilizado para la detección de la disfagia. Se realizó un análisis estadístico uni- y bivariante, a través del odds ratio (OR) para detectar los factores de riesgo en la disfagia. Resultados: 103 pacientes fueron reclutados de 401 posibles. La media de edad fue de 59,33±13,23; los hombres representaban el 76,7%. La gravedad media fue: APACHE II (12,74±6,17) y Charlson (2,98±3,31). Un 45,6% de los pacientes desarrollaron disfagia, obteniendo valores significativos de OR (p<0,050) para el desarrollo de disfagia: la mayor edad, los antecedentes neurológicos, COVID19, la alta estancia en UCI y hospitalización y la presencia de traqueotomía. Los pacientes COVID19 representaban el 46,6%, por lo que se realizó un análisis de este subgrupo observando resultados similares, con un riesgo de Charlson (OR:4,65; IC95%: 1,31-16,47; p=0,014) y una estancia hospitalaria (OR: 8,50; IC95%: 2,20-32,83; p<0,001). Al alta de UCI, el 37,9% de la población presentaba todavía disfagia, y mantenía este problema al alta hospitalaria el 12,6%. Conclusiones: Casi la mitad de nuestros pacientes presentaron disfagia. Fueron factores de riesgo la gravedad clínica y la presencia de traqueotomía. Se observó en estos pacientes una mayor estancia tanto en UCI como en hospitalización.(AU)

Aims: To identify risk factors present in patients with dysphagia in a population of critically ill patients. Methods: Case series of a cohort of patients recruited in the intensive care unit (ICU) until hospital discharge. Patients who gave consent and met the inclusion criteria were recruited. The Volume-Viscosity clinical examination method was used for the screening of dysphagia. An uni- and bivariate statistical analysis was performed using odds ratio (OR) to detect risk factors for dysphagia. Outcomes: 103 patients were recruited from 401 possible. The mean age was 59,33±13,23, men represented 76,7%. The severity of the sample was: APACHE II (12,74±6,17) and Charlson (2,98±3,31). 45,6% of patients showed dysphagia, obtaining significant OR values (p<0,050) for the development of dysphagia: older age, neurological antecedents, COVID19, long stay in ICU and hospitalization, and the presence of tracheotomy. COVID19 patients represented 46,6% of the sample, so an analysis of this subgroup was performed, showing similar results, with a Charlson risk (OR:4,65; 95% CI:1,31-16,47; p=0,014) and a hospital stay (OR: 8,50; 95%CI: 2,20-32,83; p<0,001). On discharge from the ICU, 37,9% of the population still had dysphagia; 12,6% maintained this problem at hospital discharge. Conclusions: Almost half of our patients developed dysphagia. Clinical severity and the presence of tracheotomy were risk factors. We observed in patients with dysphagia a longer stay in both ICU and hospitalization.(AU)

A model of traumatic brain injury in rats is influenced by neuroprotection of diurnal variation which improves motor behavior and histopathology in white matter myelin.

Traumatic brain injury (TBI) represents a significant public health concern and has been associated with high rates of morbidity and mortality. TBI generates two types of brain damage: primary and secondary. Secondary damage originates a series of pathophysiological processes, which include metabolic crisis, excitotoxicity, and neuroinflammation, which have deleterious consequences for neuronal function. However, neuroprotective mechanisms are also activated. The balance among these tissue responses, and its variations throughout the day determines the fate of the damage tissue. We have demonstrated less behavioral and morphological damage when a rat model of TBI was induced during the light hours of the day. Moreover, here we show that rats subjected to TBI in the dark lost less body weight than those subjected to TBI in the light, despite no change in food intake. Besides, the rats subjected to TBI in the dark had better performance in the beam walking test and presented less histological damage in the corpus callosum and the cingulum bundle, as shown by the Klüver-Barrera staining. Our results suggest that the time of day when the injury occurs is important. Thus, this data should be used to evaluate the pathophysiological processes of TBI events and develop better therapies.

Dysphagia in intensive care, a real problem: analysis of risk factors.

AIMS: To identify risk factors present in patients with dysphagia in a population of critically ill patients. METHODS: Case series of a cohort of patients recruited in the intensive care unit (ICU) until hospital discharge. Patients who gave consent and met the inclusion criteria were recruited. The Volume-Viscosity clinical examination method was used for the screening of dysphagia. An uni- and bivariate statistical analysis was performed using odds ratio (OR) to detect risk factors for dysphagia. OUTCOMES: 103 patients were recruited from 401 possible. The mean age was 59,33 ± 13,23, men represented 76,7%. The severity of the sample was: APACHE II (12,74 ± 6,17) and Charlson (2,98 ± 3,31). 45,6% of patients showed dysphagia, obtaining significant OR values (p < 0,050) for the development of dysphagia: older age, neurological antecedents, COVID19, long stay in ICU and hospitalization, and the presence of tracheotomy. COVID19 patients represented 46,6% of the sample, so an analysis of this subgroup was performed, showing similar results, with a Charlson risk (OR:4,65; 95% CI:1,31-16,47; p = 0,014) and a hospital stay (OR: 8,50; 95%CI: 2,20-32,83; p < 0,001) On discharge from the ICU, 37,9% of the population still had dysphagia; 12,6% maintained this problem at hospital discharge. CONCLUSIONS: Almost half of our patients developed dysphagia. Clinical severity and the presence of tracheotomy were risk factors. We observed in patients with dysphagia a longer stay in both ICU and hospitalization.

The diagnosis of the middle interhemispheric variant of holoprosencephaly with fetal MRI.

Congenital anomalies of the central nervous system comprise a wide spectrum of malformations associated with a wide variety of genetic syndromes and chromosomal anomalies, and they are among the principal causes of morbidity and mortality in infants. Among these anomalies, holoprosencephaly arises from the complete or partial failure of the brain to divide into the cerebral hemispheres. Imaging tests are fundamental for the prenatal diagnosis of holoprosencephaly; the diagnostic process usually starts with sonography and then the findings are refined with fetal MRI. Radiologists need to be familiar with the possible findings because the prognosis varies.

Factors of Poor Prognosis Associated with Chronic Kidney Disease by Stage in Ambulatory Patients: A Cross-sectional Study.

BACKGROUND: Mexico has a high prevalence of chronic kidney disease (CKD) but limited information about the early stages of CKD and their clusters of poor prognosis factors (PPF) such as hyperuricemia, electrolyte abnormalities or comorbidities. OBJECTIVE: To assess the prevalence of PPF by CKD stages in ambulatory patients. METHODS: A cross-sectional study with 1772 adult patients with CKD that attended the Nephrology Outpatient Clinic. PPF data is reported as adjusted OR (95% confidence interval) (CI). RESULTS: Mean age was 56.2 ± 15.8 years. Kidney Replacement Therapy (KRT) was reported in 12% of the patients. Type 2 diabetes mellitus (T2DM), age >50 years and male gender were the PPF associated with all CKD stages. The PPF in CKD 2 and 3a hyperuricemia OR 3.4 (2.02,6.0) and 4.4 (2.5,7.6), and hypertension OR 1.8 (1.01,3.4) and 2.3 (1.2,4.3) respectively. In CKD 3b were hyperuricemia OR 5.1 (3.1,8.6), hypertension OR 2.7 (1.5,4.9) and hyperkalemia OR 3.4 (1.5,7.6). For CKD 4, 5 without KRT and 5 were hyperuricemia OR 7.02 (4.1,11.8), 13.5 (7.4,24.6), 3.9 (2.2-6.9), hypertension OR 3.4 (1.9,6.1), 3.4 (1.9,6.1), 3.8 (2.1,7.1), and hyperkalemia 2.9 (1.3,6.3), 7.9 (3.6,17.3), 8.7 (3.9,19.3), respectively. Anemia was important for CKD 5 without KRT and 5 with OR of 5.7 (3.09,10.6) and 8 (4.2,15), respectively. CONCLUSIONS: This is the largest study of Mexican patients with CKD; most of them without KRT. Patients had multiple modifiable PPF. Early and comprehensive management of PPF could prevent or delay progression to KRT. Treatment of associated PPF should be a priority, as it could make a significant difference both for CKD progression and its subsequent cardiovascular risk.

Variante interhemisférica media de holoprosencefalia: diagnóstico mediante resonancia magnética fetal / The diagnosis of the middle interhemispheric variant of holoprosencephaly with fetal MRI

Las anomalías congénitas del sistema nervioso central constituyen un amplio grupo de malformaciones asociadas a una gran variedad de síndromes genéticos y anomalías cromosómicas, y una de las principales causas de morbimortalidad infantil. Dentro de ellas, la holoprosencefalia conlleva un trastorno de la diferenciación del prosencéfalo, con una falta completa o parcial de división entre los hemisferios cerebrales. Para su diagnóstico prenatal es fundamental la realización de pruebas de imagen y el conocimiento de los posibles hallazgos, debido a que su pronóstico es variable, comenzando normalmente con la ecografía y confirmando lo visualizado con la resonancia magnética.(AU)

Congenital anomalies of the central nervous system comprise a wide spectrum of malformations associated with a wide variety of genetic syndromes and chromosomal anomalies, and they are among the principal causes of morbidity and mortality in infants. Among these anomalies, holoprosencephaly arises from the complete or partial failure of the brain to divide into the cerebral hemispheres. Imaging tests are fundamental for the prenatal diagnosis of holoprosencephaly; the diagnostic process usually starts with sonography and then the findings are refined with fetal MRI. Radiologists need to be familiar with the possible findings because the prognosis varies.(AU)

New silica based adsorbent material from rice straw and its in-flow application to nitrate reduction in waters: Process sustainability and scale-up possibilities.

This paper shows a particular example to move to a sustainable circular economical process from valorization of rice straw ashes by developing a green synthesis for obtaining a useful sub-product. This strategy can palliate negative effects of the agriculture waste practices on the environment and also the obtained silica reduced nitrate content in waters. It is demonstrated that the silica synthesis developed at lab was scalable more than a hundred times with good results. Adsorption studies of nitrate in standards and real well waters at lab scale and scaling-up provided similar results. Adsorption values near to 15 mg/g for nitrate standards and 8.5 mg/g for well water were obtained until achieving the initial nitrate concentration. Experimental breakthrough curves fitted to Thomas model, which gave similar results for adsorption capacities. The adsorption capacity was checked with that obtained by a commercial resin, providing improved results. The method at large scale was compared with industrial traditional methods and green adsorbents.

The diagnosis of the middle interhemispheric variant of holoprosencephaly with fetal MRI. / Variante interhemisférica media de holoprosencefalia: diagnóstico mediante resonancia magnética fetal.

Congenital anomalies of the central nervous system comprise a wide spectrum of malformations associated with a wide variety of genetic syndromes and chromosomal anomalies, and they are among the principal causes of morbidity and mortality in infants. Among these anomalies, holoprosencephaly arises from the complete or partial failure of the brain to divide into the cerebral hemispheres. Imaging tests are fundamental for the prenatal diagnosis of holoprosencephaly; the diagnostic process usually starts with sonography and then the findings are refined with fetal MRI. Radiologists need to be familiar with the possible findings because the prognosis varies.

In-tube solid phase microextraction coupled to miniaturized liquid chromatography for both, noble metal nanoparticle assessment and sensitive plasmonic assay development.

Colorimetric localized surface plasmon resonance (LSPR) as analytical response is applied for a wide number of chemical sensors and biosensors. However, the dependence of different factors, such as size distribution of nanoparticles (NPs), shape, dielectric environment, inter-particle distance and matrix, among others, can provide non-reliable results by UV-vis spectrometry in complex matrices if NP assessment is not carried out, particularly at low levels of analyte concentrations. Miniaturized liquid chromatography, capillary (CapLC) and nano (NanoLC), coupled on line with in-tube solid phase microextraction (IT-SPME) is proposed for the first time for both, controlling suitability of used noble metal NP dispersions and developing plasmonic assays. Several capped noble NPs and target analytes were tested from variations in the chromatographic profiles obtained by using diode array detection. The IT-SPME step, which influenced the chromatographic fingerprint provided by noble NP dispersions, was studied by asymmetrical flow field flow fractionation (AF4) too. We monitored NP aggregation induced by interaction with several analytes like acids and spermine (SPN). Assessment of NPs was achieved in less than 10 min and it permitted to develop suitable plasmonic tests. Here, it was also demonstrated that these assays can be followed by IT-SPME-miniaturized LC-DAD and more sensitivity and selectivity than those provided by UV-Vis spectrometry were achieved. Analysing urine samples to determine SPN as a cancer biomarker as a proof of concept is presented.

Impact of the COVID-19 pandemic on the activity of the Radiological Emergency Department: the experience of the Maggiore della Carità Hospital in Novara.

PURPOSE: During the first peak of the COVID-19 pandemic, the activity of Emergency Departments worldwide changed dramatically, focusing on diagnosis and care of the Sars-Cov-2 associated disease. These major changes also involved the activity of the Emergency Radiology Department (ERD). This study aimed to analyse the impact of the COVID-19 pandemic on imaging studies, both in terms of the amount, frequency and subspecialty of different imaging modalities requested to the ERD of the Maggiore della Carità Hospital in Novara (Italy). METHODS: To this end, our observational study took into account the imaging studies requested by the emergency department during three-time spans. These were defined as phase 0 (pre-pandemic), phase 1 (pandemic peak with complete lockdown) and phase 2 (post-pandemic peak with partial lifting of restrictive measures), as derived from Italian urgent decrees by the President of the Council of Ministers (DPCM) which established the duration and entity of the lockdown measures throughout the pandemic. The dataset was processed and then compared with Pearson's chi-squared test. RESULTS: During the pandemic peak, our data showed a significant drop in the total number of studies requested and a significant rise in computed tomography (CT) studies. In particular, a statistically significant increase in chest CT studies was found, probably due to the high sensitivity of this imaging method in identifying pulmonary involvement during respiratory tract infection of possible viral etiology (SARS-Cov-2). Moreover, we observed a statistically significant decrease of X-ray (XR) and ultrasound (US) studies during phase 1 compared to phase 0 and phase 2 probably due to a reduction in the numbers of ER visits for minor traumas given the mobility restrictions and people hesitancy in visiting the ER due to fear of contagion. CONCLUSIONS: We can conclude that the activity of the ERD was heavily impacted by the SARS-Cov-2 pandemic. Further studies will be needed to estimate the impact of the pandemic on public health in terms of excess mortality related to delayed diagnosis and care of non-COVID diseases.

Strategies to Produce Grapefruit-Like Citrus Varieties With a Low Furanocoumarin Content and Distinctive Flavonoid Profiles.

Pummelos and hybrids, such as grapefruits, have high furanocoumarin and low flavonoid contents. Furanocoumarins interact negatively with certain drugs, while flavonoids are antioxidant compounds with health benefits. To obtain new grapefruit-like varieties with low furanocoumarin and high flavonoid contents, diploid and triploid hybrid populations from crosses between diploid and tetraploid "Clemenules" clementine and diploid "Pink" pummelo were recovered and analyzed. With regard to furanocoumarins, triploids produce less bergapten, bergamottin and 6,7-DHB than diploids. Regarding flavonoids, triploids yielded more eriocitrin, narirutin, hesperidin and neohesperidin than diploids, whereas no differences were observed in neoeriocitrin and naringin. These results indicate that, the strategy to recover triploid hybrids by 4x × 2x crosses is more appropriate than the recovery of diploid hybrids by 2x × 2x crosses for obtaining grapefruit-like varieties of citrus with lower furanocoumarin and higher flavonoid contents.

Risk assessment of arterial allograft contamination from tissue donors colonized by Candida auris.

BACKGROUND: Microbiological contamination is one of the main risks that must be controlled in tissue banking practices. For this reason, strict donor selection criteria are applied, disinfection protocols are used, and microbiological monitoring is performed at various stages. AIM: To detect Candida auris in arterial allografts and assess its origin. METHODS: Data on two multi-tissue donations with positive microbiological cultures for C. auris were analysed. Risk factors for microbiological contamination were assessed at procurement, processing and post storage. FINDINGS: C. auris was only isolated in cultures from arteries, and was not detected in cultures from cornea, musculoskeletal tissue or skin (even in the axillary-rectal sample taken from one donor). CONCLUSION: The donor's own skin was identified as the most likely source to explain the contamination of arteries by C. auris. Due to the pathogenicity of this fungus and difficulties associated with its correct identification, the implementation of measures for its detection in tissue donations is recommended.

Respiratory function in patients post-infection by COVID-19: a systematic review and meta-analysis.

BACKGROUND: Evidence suggests lungs as the organ most affected by coronavirus disease 2019 (COVID-19). The literature on previous coronavirus infections reports that patients may experience persistent impairment in respiratory function after being discharged. Our objective was to determine the prevalence of restrictive pattern, obstructive pattern and altered diffusion in patients post-COVID-19 infection and to describe the different evaluations of respiratory function used with these patients. METHODS: A systematic review was conducted in five databases. Studies that used lung function testing to assess post-infection COVID-19 patients were included for review. Two independent reviewers analysed the studies, extracted the data and assessed the quality of evidence. RESULTS: Of the 1973 reports returned by the initial search, seven articles reporting on 380 patients were included in the data synthesis. In the sensitivity analysis, we found a prevalence of 0.39 (CI 0.24-0.56, p < 0.01, I2 = 86%), 0.15 (CI 0.09-0.22, p = 0.03, I2 = 59%), and 0.07 (CI 0.04-0.11, p = 0.31, I2 = 16%) for altered diffusion capacity of the lungs for carbon monoxide (DLCO), restrictive pattern and obstructive pattern, respectively. CONCLUSION: Post-infection COVID-19 patients showed impaired lung function; the most important of the pulmonary function tests affected was the diffusion capacity.