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.

Efecto de la variante Ómicron sobre la incidencia y la letalidad durante la 6 onda epidémica COVID-19 en España / Effect of the Omicron variant on cumulative incidence of infection and lethality during the sixth wave of the COVID-19 epidemic in Spain

La pandemia COVID-19 ha puesto a prueba los sistemas sanitarios a nivel mundial. Las sucesivas ondas epidémicas han mostrado características diferentes. La variante Ómicron del SARS-CoV-2 modificó el comportamiento epidémico que habían seguido las variantes previas. El objetivo de este análisis fue determinar las características epidemiológicas de la COVID-19 durante la 6.ª onda epidémica y sus diferencias según predominara las variantes Delta u Ómicron. Se analizaron los datos epidemiológicos correspondientes a la 6.ª onda epidémica publicados por los organismos oficiales, y se analizaron la incidencia acumulada de infección (IA-I) y las tasas de letalidad (TL), tanto del conjunto de España como de las diferentes Comunidades Autónomas, en el conjunto de la población y por grupos etarios. Los resultados mostraron que la IA-I era mayor con la variante Ómicron (10,89 vs. 0,75% con Delta) mientras que la TL lo era con la variante Delta (4,2 vs. 1,3‰ con Ómicron), así como una mayor tasa de hospitalización e ingreso en UCI con la variante Delta.(AU)

The COVID-19 pandemic has strained healthcare systems globally. The successive epidemic waves have shown different characteristics. The Omicron variant of SARS-CoV-2 modified the epidemic behavior that previous variants had followed. The aim of this analysis was to determine the epidemiological characteristics of COVID-19 during the sixth epidemic wave and its differences according to the predominance of the Delta or Omicron variants. The epidemiological data corresponding to the sixth wave of the epidemic published by official organizations were analyzed, and the cumulative incidence of infection (CI-I) and case fatality rates (CFR) were calculated, both for Spain as a whole and for the different Autonomous Communities, in the population as a whole and by age groups. The results showed that the CI-I was higher with the Ómicron variant (10.89% vs 0.75% with Delta) while the CFR was higher with the Delta variant (4.2‰ vs 1.3‰ with Ómicron), as well as a higher rate of hospitalization and ICU admission with the Delta variant.(AU)

[Effect of the Omicron variant on cumulative incidence of infection and lethality during the sixth wave of the COVID-19 epidemic in Spain]. / Efecto de la variante Ómicron sobre la incidencia y la letalidad durante la 6.ª onda epidémica COVID-19 en España.

The COVID-19 pandemic has strained healthcare systems globally. The successive epidemic waves have shown different characteristics. The Omicron variant of SARS-CoV-2 modified the epidemic behavior that previous variants had followed. The aim of this analysis was to determine the epidemiological characteristics of COVID-19 during the sixth epidemic wave and its differences according to the predominance of the Delta or Omicron variants. The epidemiological data corresponding to the sixth wave of the epidemic published by official organizations were analyzed, and the cumulative incidence of infection (CI-I) and case fatality rates (CFR) were calculated, both for Spain as a whole and for the different Autonomous Communities, in the population as a whole and by age groups. The results showed that the CI-I was higher with the Ómicron variant (10.89% vs 0.75% with Delta) while the CFR was higher with the Delta variant (4.2‰ vs 1.3‰ with Ómicron), as well as a higher rate of hospitalization and ICU admission with the Delta variant.

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.

The role of SepF in cell division and diazotrophic growth in the multicellular cyanobacterium Anabaena sp. strain PCC 7120.

The cyanobacterium Anabaena forms filaments of cells that grow by intercalary cell division producing adjoined daughter cells connected by septal junction protein complexes that provide filament cohesion and intercellular communication, representing a genuine case of bacterial multicellularity. In spite of their diderm character, cyanobacterial genomes encode homologs of SepF, a protein normally found in Gram-positive bacteria. In Anabaena, SepF is an essential protein that localized to the cell division ring and the intercellular septa. Overexpression of sepF had detrimental effects on growth, provoking conspicuous alterations in cell morphology that resemble the phenotype of mutants impaired in cell division, and altered the localization of the division-ring. SepF interacted with FtsZ and with the essential FtsZ tether ZipN. Whereas SepF from unicellular bacteria generally induces the bundling of FtsZ filaments, Anabaena SepF inhibited FtsZ bundling, reducing the thickness of the toroidal aggregates formed by FtsZ alone and eventually preventing FtsZ polymerization. Thus, in Anabaena SepF appears to have an essential role in cell division by limiting the polymerization of FtsZ to allow the correct formation and localization of the Z-ring. Expression of sepF is downregulated during heterocyst differentiation, likely contributing to the inhibition of Z-ring formation in heterocysts. Finally, the localization of SepF in intercellular septa and its interaction with the septal-junction related proteins SepJ and SepI suggest a role of SepF in the formation or stability of the septal complexes that mediate cell-cell adhesion and communication, processes that are key for the multicellular behavior of Anabaena.

Medial incisional ventral hernia repair with Adhesix® autoadhesive mesh: descriptive study.

Nowadays, the gold standard for the surgical treatment of abdominal wall defects is the use of a mesh. There is an extensive variety of meshes, self-adhesive ones being among the most novel technologies. The literature on the self-adhesive mesh Adhesix® (Cousin Biotech Laboratory, 59117 Wervicq South, France) in medial incisional ventral hernia is scarce. We performed a retrospective descriptive study with prospective data collection from 125 patients who underwent prosthetic repair of medial incisional ventral hernia-M1-M5 classification according to European Hernia Society (EHS)-with self-adhesive mesh Adhesix® between 2013 and 2021. Follow-up was performed 1 month and yearly after the surgery. Postoperative complications and hernia recurrences were recorded. Epidemiological results were average BMI 30.5 kg/m2 (SD 5), highlighting that overweight (41.6%) and obesity type 1 (25.6%) were the most represented groups. 34 patients (27.2%) had already undergone a previous abdominal wall surgery. The epigastric-umbilical (M2-M3 EHS classification, 22.4%) and umbilical (M3 EHS classification, 20%) hernias were the predominant groups. The elective surgery technique was Rives or Rives-Stoppa with an associated supraaponeurotic mesh if the closure of the anterior aponeurosis of the rectus sheath was not surgically closed (13 patients). The most frequent postoperative complication was seroma (26.4%). The recurrence rate was 7.2%. The average follow-up length was 2.6 years (SD 1.6 years). According to the results of this study and the literature available, we consider that the self-adhesive mesh Adhesix® is an appropriate alternative mesh option for the repair of medial incisional ventral hernias.

Selecting optimal R6TX2 intermetallics (R = Gd, Tb, Dy; T = Mn, Fe, Co, Ni; X = Sb, Te) for magnetic refrigeration.

A complete experimental study of the physical properties playing a relevant role in the magnetic refrigeration application (structural, magnetic, magnetocaloric and thermal) has been performed over nine selected Fe2P-type R6TX2 (R = Gd, Tb, Dy; T = Mn, Fe, Co, Ni; X = Sb, Te) intermetallic compounds, to work close to room temperature. Two magnetic phase transitions are observed for these materials: a paramagnetic to ferromagnetic transition in the range of 182-282 K and a spin reorientation transition in the range of 26-76 K. As a consequence, two peaks related to a direct magnetocaloric effect (DMCE) appear with the magnetic entropy change, generating a wide table-like plateau region in between both peaks, which is required to improve the efficiency of refrigerators following an Ericsson cycle. The highest magnetic entropy peak value for µ0ΔH = 5 T is found for Tb2Dy4FeSb2, with 7.72 J kg-1 K-1 around 182 K. For the same applied field the other compounds show moderate values around room temperature (2.88-4.53 J kg-1 K-1). However, the superposition of the two peaks results in huge refrigerant capacity values, up to RCFWHM(5 T) = 1103.04 J kg-1 in the case of Tb2Dy4FeSb2. The thermal diffusivity, thermal effusivity, thermal conductivity and specific heat capacity have been measured at room temperature, and the temperature dependence of the former has been obtained around the relevant magnetic phase transition region, with values in the range of 1.3-2.3 mm2 s-1, which are good for magnetic refrigerators at high working frequencies. The study is completed with a rigorous critical behavior analysis of the second order PM-FM transition. The critical exponent γ points to long range order interactions, in general, while ß values are in the range of 0.59-0.90, indicating a deviation from theoretical models as a reflection of the magnetic complexity in these compounds. The critical exponents have been used to confirm the scaling relations of magnetocaloric properties, and the scaling of refrigerant capacity (RC) values in materials exhibiting two magnetic phase transitions is addressed, concluding that for a correct scaling of RC the magnetic entropy change peak must be considered symmetric. The role of each atom in the properties of the compounds is discussed.

Development and validation of a minimally invasive and image-guided tape stripping method to sample atopic skin in children.

BACKGROUND: Molecular skin profiling techniques, typically performed on skin samples taken by punch biopsy, have enhanced the understanding of the pathophysiology of atopic dermatitis (AD), thereby enabling the development of novel targeted therapeutics. However, punch biopsies are not always feasible or desirable, and novel minimally invasive methods such as skin tape stripping have been developed. AIM: To develop, optimize and validate a novel tape stripping method guided by noninvasive in vivo skin imaging to sample atopic skin in children. METHODS: Skin tape stripping-based procedures were compared and optimized using data from 30 healthy controls (HCs: 5 adults, 25 children) and 39 atopic children. Evaluations were guided by high-resolution photography, reflectance confocal microscopy, optical coherence tomography and transepidermal water loss measurements. We assessed and compared adverse events (AEs), the time needed to perform the sampling and the cDNA levels obtained from the tapes. RESULTS: Tape stripping methods based on previously described protocols resulted in erosions in all participants and required a median time of 65 min to perform (range 60-70 min), but provided good cDNA yield. Shorter durations appeared less invasive but provided lower cDNA yield. The final optimized tape stripping protocol, using 11 tapes of 22 mm in diameter, each applied twice for 5 s with 90° rotation, did not produce significant AEs, was completed within a median time of 7 min (range 5-15 min) and provided good cDNA yield both in HCs and atopic children. CONCLUSION: Our minimally invasive method is safe and reliable, and provides reproducible acquisition of cDNA in atopic children. In addition, it enables rapid sample collection, a crucial factor in clinical practice.

Liderazgo de la mujer en la investigación clínica: estudio observacional retrospectivo durante dos décadas en España / Women's leadership in clinical research: A retrospective observational study over two decades in Spain

Antecedentes y objetivo Los datos disponibles avalan las diferencias por género en el liderazgo de las investigaciones clínicas (IC). Este estudio analiza en qué medida las mujeres lideran estas investigaciones. Materiales y métodos Estudio observacional retrospectivo en un hospital universitario terciario asociado a uno de los institutos de investigación sanitaria más importantes de España. Analizamos los investigadores principales (IP) por género (2001-2020). Variable principal: proporción de IC lideradas por mujeres durante el período de estudio. Variables secundarias: diferencias de IP por género según el tipo de estudio: ensayos clínicos (EC) o estudios de no-intervención (ENI) y según la financiación. Fuentes de datos: registros del Comité de Ética en Investigación con medicamentos (CEIm) y del Departamento de Recursos Humanos. Resultados Durante el estudio, el CEIm aprobó 8.466 protocolos; el 52% (4.408/8.466) fueron EC y el resto, ENI. Las mujeres lideraron un 39,7% (3.360/8.466) del total. La brecha de género se observó principalmente en EC: las mujeres fueron IP de un 31,5% de ellos (1.391/4.408) y de un 48,5% (1.969/4.058) de los ENI. Ello a pesar de la tendencia creciente del número de facultativas. Los estudios de financiación privada fueron más comúnmente liderados por hombres. Conclusiones Nuestros resultados demuestran que existe una infrarrepresentación de las mujeres en puestos de liderazgo en la investigación, principalmente en aquellos con financiación privada. Este estudio refuerza la idea de que todavía queda un largo camino por recorrer en este campo. Se necesitan más estudios para la identificación de diferencias existentes que permitan implantar cambios a nivel institucional y cultural que promuevan la igualdad de género en el ámbito de la investigación clínica (AU)

Background and objective Available data support differences by gender in the leadership of clinical investigations (CI). This study analyzes to what extent women lead these investigations. Materials and method Observational-retrospective study in a tertiary university hospital associated with one of the most important health research institutes in Spain. We analyzed the principal investigators (PI) by gender from 2001 to 2020. Main outcome: proportion of CI led by female doctors (FD) during the study period. Secondary outcomes: differences in PI by gender according to the type of study: clinical trials (CT) or non-interventional-researches (NIR) and according to type of funding. Data sources: Research Ethics Committee (REC) and Human Resources Department registries. Result During the study, the REC approved 8,466 protocols, 52% (4,408/8,466) were EC, the rest were NIR. Women led 39.7% (3,360/8,466) of the total. The gender gap was observed mainly in EC: FD were IP of 31.5% of them (1,391/4,408) and 48.5% (1,969/4,058) of NIR. This despite the increasing trend in the number of FD staff. By type of funding, when the studies were supported by private sector there was a wider gap markedly unfavorable for women. Conclusions Our results show that there is underrepresentation of women in research leadership, mainly those with private financing. This study reinforces the idea that there is still a long way to go in this field. More studies are necessary to identify the existing differences that allow the implementation of actions at the institutional and cultural level that promote gender equality in the field of clinical research (AU)

Women's leadership in clinical research: A retrospective observational study over two decades in Spain.

BACKGROUND AND OBJECTIVE: Available data support differences by gender in the leadership of clinical investigations (CI). This study analyzes to what extent women lead these investigations. MATERIALS AND METHODS: Observational-retrospective study in a tertiary university hospital associated with one of the most important health research institutes in Spain. We analyzed the principal investigators (PI) by gender from 2001 to 2020. MAIN OUTCOME: proportion of CI led by female doctors (FD) during the study period. SECONDARY OUTCOMES: differences in PI by gender according to the type of study: clinical trials (CT) or non-interventional-researches (NIR) and according to type of funding. DATA SOURCES: Research Ethics Committee (REC) and Human Resources Department registries. RESULTS: During the study, the REC approved 8466 protocols, 52% (4408/8466) were EC, the rest were NIR. Women led 39.7% (3360/8466) of the total. The gender gap was observed mainly in EC: FD were IP of 31.5% of them (1391/4408) and 48.5% (1969/4058) of NIR. This despite the increasing trend in the number of FD staff. By type of funding, when the studies were supported by private sector there was a wider gap markedly unfavorable for women. CONCLUSIONS: Our results show that there is underrepresentation of women in research leadership, mainly those with private financing. This study reinforces the idea that there is still a long way to go in this field. More studies are necessary to identify the existing differences that allow the implementation of actions at the institutional and cultural level that promote gender equality in the field of clinical research.

French legislation on retrospective clinical research: What to know and what to do.

The French legislation on human subject research known as the Jardé law of 5th March 2012 has been applicable since November 2016. It concerns all research involving human subjects (RIPH, in French) and is defined according to 3 categories: high-risk interventional RIPH, low-risk interventional RIPH and non-interventional RIPH. This recent development in the supervision of research on human subjects had several objectives: to redefine the various categories of research, to strengthen data protection and to effectively address the ethical guidelines of international journals. The levels of constraint differ between categories of research according to level of risk, the common objective being to ensure patient protection. Retrospective studies based on information drawn from medical records or other databases, which are widely used in the surgical field, are not covered by the Jardé law. However, they require approval by local ethics committees and compliance with European legislation on personal data protection. Simplified procedures have been set up by the research and innovation departments in our university hospitals. In this update, we shall synthesize the legal prerequisites applying to retrospective studies on data from medical files.

Pulsioximetría: papel en el paciente COVID-19 domiciliario / Pulse oximetry: Role in the COVID-19 patient at home

La COVID-19 se comporta como una enfermedad heterogénea. Algunos pacientes pueden presentar hipoxemia sin disnea durante su evolución (hipoxemia silente). La pulsioximetría juega un papel crucial en la detección de la hipoxemia en estos pacientes, especialmente cuando permanecen en su domicilio. Pacientes con niveles de SpO2 ≤ 92% o desaturaciónes ≥ 3% tras el ejercicio precisan de ingreso hospitalario. Los descensos progresivos de la saturación que alcancen niveles SpO2 < 96% precisan de valoración clínica estricta (estudio radiológico, analítica sanguínea) para lo que será enviado a un centro sanitario (AU)

COVID-19 behaves like a heterogeneous disease. Some patients may develop dyspnea-free hypoxemia during its evolution (silent hypoxemia). Pulse oximetry plays a crucial role in detecting hypoxemia in these patients, especially when they remain at home. Patients with SpO2 levels ≤ 92% or desaturations ≥ 3% after exercise test require hospital admission. Progressive saturation declines reaching SpO2 levels < 96% require strict clinical assessment (radiological study, blood test) for which it will be sent to a health center (AU)

Comparative study of biological versus synthetic prostheses in the treatment of ventral hernias classified as grade II/III by the Ventral Hernia Working Group.

AIM OF THE STUDY: The implantation of biological prostheses in an at-risk environment has seen increasing use. Their markedly higher cost compared to synthetic prostheses makes it important to analyse their usefulness in terms of actual benefit and cost-effectiveness. This study aims to examine the relevance of bioprostheses during surgical repair of Grade II/III ventral hernias as classified by the Ventral hernia working group (VHWG). MATERIALS AND METHODS: This study analysed the data of 119 patients requiring non-emergency repair of VHWG II/III grade hernias between 2010 and 2017. The results of patients who were treated with a bioprosthesis (n=59) were compared to those receiving a synthetic prosthesis (n=60). The primary outcome was surgical site infection (SSI) at 90 days. The secondary endpoints were hernia recurrence rate, cost of the prosthesis, duration of hospital stay and re-hospitalisation rate. RESULTS: The two groups were shown to be comparable by analysis of demographic, pre- and intraoperative data. The SSI rate was significantly higher in the bioprosthesis group (20% vs. 7%; P=0.010), as was the recurrence rate (56% vs. 28%; P=0.003) with a median follow-up of 40 months. The cost of the bioprosthesis was significantly higher than that of the synthetic prosthesis (€3363 vs. €249; P<0.010). CONCLUSION: In this retrospective study, the use of a bioprosthesis for repair of VHWG II/III ventral hernias was associated with a higher rate of both SSI and hernia recurrence at a cost 13 times greater than the use of a synthetic prosthesis.

[Pulse oximetry: Role in the COVID-19 patient at home]. / Pulsioximetría: papel en el paciente COVID-19 domiciliario.

COVID-19 behaves like a heterogeneous disease. Some patients may develop dyspnea-free hypoxemia during its evolution (silent hypoxemia). Pulse oximetry plays a crucial role in detecting hypoxemia in these patients, especially when they remain at home. Patients with SpO2 levels ≤ 92% or desaturations ≥ 3% after exercise test require hospital admission. Progressive saturation declines reaching SpO2 levels < 96% require strict clinical assessment (radiological study, blood test) for which it will be sent to a health center.