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.

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.

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.

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.

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.

SEOM clinical guidelines in hereditary breast and ovarian cancer (2019).

Mutations in BRCA1 and BRCA2 high penetrance genes account for most hereditary breast and ovarian cancer, although other new high-moderate penetrance genes included in multigene panels have increased the genetic diagnosis of hereditary breast and ovarian cancer families by 50%. Multigene cancer panels provide new challenges related to increased frequency of variants of uncertain significance, new gene-specific cancer risk assessments, and clinical recommendations for carriers of mutations of new genes. Although clinical criteria for genetic testing continue to be largely based on personal and family history with around a 10% detection rate, broader criteria are being applied with a lower threshold for detecting mutations when there are therapeutic implications for patients with breast or ovarian cancer. In this regard, new models of genetic counselling and testing are being implemented following the registration of PARP inhibitors for individuals who display BRCA mutations. Massive sequencing techniques in tumor tissue is also driving a paradigm shift in genetic testing and potential identification of germline mutations. In this paper, we review the current clinical criteria for genetic testing, as well as surveillance recommendations in healthy carriers, risk reduction surgical options, and new treatment strategies in breast cancer gene-mutated carriers.

A novel method to teach and assess the sterility of donning sterile gloves.

Sterility is of utmost importance during surgery, particularly orthopaedic surgery. The literature suggests sterility, when compromised, is frequently contaminated at the point of donning sterile gowns and gloves. We describe a novel method to assess the compliance of sterility whilst applying surgical gloves using an ultraviolet lightbox and an ultraviolet-sensitive 'Germ paint'. We carried out an audit of 'sterility' using this method with our surgical trainees. A subsequent educational programme described methods of glove-donning. Repeat assessment yielded significantly improved results. Educating staff using this method may improve sterility in theatre. We believe this is a novel method to teach and assess sterility during glove-donning. The equipment is readily accessible within each NHS hospital. Medical and theatre staff should use this as part of training and departmental induction programmes.

[Heterogeneity amongst different diagnostic tools in frailty screening]. / Heterogeneidad en el cribado poblacional de la fragilidad.

BACKGROUND: Frailty means a state of vulnerability with a predisposition to adverse health outcomes, closely related to age and a consequent loss of functional capability. Early detection is important for initiating measures to slow its progression. Primary Health Care (PHC) occupies a privileged place in this. However, we do not possess a gold standard tool for its detection. Our aim is to analyse the prevalence of frailty in PHC and define the most useful diagnostic tool for this area. METHODS: Cross-sectional study with 225 people were selected from a population of 4,252 people aged over 75 years-old, from three different basic health zones of Navarre. Four different diagnostic tests for frailty were conducted: the Fried phenotype, the Short Physical Performance Battery (SPPB), the Timed Up-to-Go test (TUG) and the Gait Speed test (GS). Patients who were unable to finish any of the tests weren't included in the subsequent analysis. RESULTS: Fifty-one percent of participants were men, with mean age 80.5 years-old, 80% were taking more than five daily drugs, 8.4% had cognitive impairment, and 31.1 and 41.3% were independent for basic and instrumental activities, respectively, of daily living. The frailty prevalence was 8.3% for Fried phenotype, 13.7% for SPPB, 46.2% for TUG and 52.2% for Gait Speed. CONCLUSION: Great heterogeneity in the prevalence of frailty was shown depending on the tool employed. As a reliable, fast and simple tool for early detection of frailty is needed in PHC, based on our results and the particularities of PHC, we propose TUG or GS as good early predictors of this decline.

BRAF mutation is not associated with an increased risk of recurrence in patients undergoing resection of colorectal liver metastases.

BACKGROUND: BRAF mutation is associated with a poor prognosis in patients with metastatic colorectal cancer. For patients with resectable colorectal liver metastases (CRLMs), the prognostic impact of BRAF mutation is unknown and the benefit of surgery debated. This nationwide intergroup (ACHBT, FRENCH, AGEO) study aimed to evaluate the oncological outcome of patients undergoing liver resection for BRAF-mutated CRLMs. METHODS: The study included patients who underwent resection for BRAF-mutated CRLMs in 24 centres between 2012 and 2016. A case-matched comparison was made with 183 patients who underwent resection of CRLMs with wild-type BRAF during the same interval. RESULTS: Sixty-six patients who underwent resection for BRAF-mutated CRLMs in 24 centres were compared with 183 patients with wild-type BRAF. The 1- and 3-year disease-free survival (DFS) rates were 46 and 19 per cent for the BRAF-mutated group, and 55·4 and 27·8 per cent for the group with wild-type BRAF (P = 0·430). In multivariable analysis, BRAF mutation was not associated with worse DFS (hazard ratio 1·16, 95 per cent c.i. 0·72 to 1·85; P = 0·547). The 1- and 3-year overall survival rates after surgery were 94 and 54 per cent respectively among patients with BRAF mutation, and 95·8 and 82·9 per cent in those with wild-type BRAF (P = 0·004). Median survival after disease progression was 23·0 (95 per cent c.i. 11·0 to 35·0) months among patients with mutated BRAF and 44·3 (35·9 to 52·6) months in those with wild-type BRAF (P = 0·050). Multisite disease progression was more common in the BRAF-mutated group (48 versus 29·8 per cent; P = 0·034). CONCLUSION: These results support surgical treatment for resectable BRAF-mutated CRLM, as BRAF mutation by itself does not increase the risk of relapse after resection. BRAF mutation is associated with worse survival in patients whose disease relapses after resection of CRLM, as for non-metastatic colorectal cancer.

Occurrence and exposure of 3-monochloropropanediol diesters in edible oils and oil-based foodstuffs from the Spanish market.

During the industrial refining process of edible oils and the manufacture of oil-based foodstuff, contaminants such as 3-monochloropropanediol (3-MCPD) fatty acid diesters can be produced. One hundred samples of different edible oils and related fatty food purchased from local Spanish markets were analyzed to evaluate the occurrence of these contaminants. Data of seven 3-MCPD diesters together with corresponding total 3-MCPD equivalents are presented. The procedure is based on a modified QuEChERS protocol followed by LC-MS/MS analysis. Extra virgin olive oil (EVOO) and unrefined oils did not contain detectable levels of the target analytes. The highest levels of 3-MCPD diesters were found in palm oils, for 1,2-Dilinoleoyl-3-chloropropanediol (LILI) and 1-2-Bispalmitoyl-3-chloropropanediol (PAPA) with concentrations close to 10 mg kg-1 and in the lipid fraction of margarines (8.09, 3.77 and 3.72 mg kg-1 for LILI, PAPA and 1-Oleoyl-2-linoleoyl-3-chloropropanediol (OLLI), respectively).

Complex Gill Disease: an Emerging Syndrome in Farmed Atlantic Salmon (Salmo salar L.).

Gill disorders have become a significant problem during the marine phase of farming Atlantic salmon (Salmo salar L.). The term complex gill disease (CGD) includes a wide range of clinical gill disease presentations generally occurring from the end of summer to early winter on marine Atlantic salmon farms. The gross and histological lesions observed are the resultant culmination of exposure to a mixture of environmental insults, pathogenic organisms and farm management practices. None of the three principal agents purportedly associated with CGD (Desmozoon lepeophtherii, salmon gill poxvirus or Candidatus Branchiomonas cysticola) have been cultured successfully in-vitro, so individual in-vivo challenge studies to identify their pathogenesis have not been possible. Studies of cohabitation of single pathogen-infected fish with naïve fish, and epidemiological investigations are required urgently to elucidate the roles of these pathogens and other factors in CGD.

A dust-enshrouded tidal disruption event with a resolved radio jet in a galaxy merger.

Tidal disruption events (TDEs) are transient flares produced when a star is ripped apart by the gravitational field of a supermassive black hole (SMBH). We have observed a transient source in the western nucleus of the merging galaxy pair Arp 299 that radiated >1.5 × 1052 erg at infrared and radio wavelengths but was not luminous at optical or x-ray wavelengths. We interpret this as a TDE with much of its emission reradiated at infrared wavelengths by dust. Efficient reprocessing by dense gas and dust may explain the difference between theoretical predictions and observed luminosities of TDEs. The radio observations resolve an expanding and decelerating jet, probing the jet formation and evolution around a SMBH.

Delay in starting radiotherapy due to neoadjuvant therapy does not worsen survival in unresected glioblastoma patients.

PURPOSE: We retrospectively examined the potential effect on overall survival (OS) of delaying radiotherapy to administer neoadjuvant therapy in unresected glioblastoma patients. PATIENTS AND METHODS: We compared OS in 119 patients receiving neoadjuvant therapy followed by standard treatment (NA group) and 96 patients receiving standard treatment without neoadjuvant therapy (NoNA group). The MaxStat package of R identified the optimal cut-off point for waiting time to radiotherapy. RESULTS: OS was similar in the NA and NoNA groups. Median waiting time to radiotherapy after surgery was 13 weeks for the NA group and 4.2 weeks for the NoNA group. The longest OS was attained by patients who started radiotherapy after 12 weeks and the shortest by patients who started radiotherapy within 4 weeks (12.3 vs 6.6 months) (P = 0.05). OS was 6.6 months for patients who started radiotherapy before the optimal cutoff of 6.43 weeks and 19.1 months for those who started after this time (P = 0.005). Patients who completed radiotherapy had longer OS than those who did not, in all 215 patients and in the NA and NoNA groups (P = 0.000). In several multivariate analyses, completing radiotherapy was a universally favorable prognostic factor, while neoadjuvant therapy was never identified as a negative prognostic factor. CONCLUSION: In our series of unresected patients receiving neoadjuvant treatment, in spite of the delay in starting radiotherapy, OS was not inferior to that of a similar group of patients with no delay in starting radiotherapy.

The relationship between frailty and polypharmacy in older people: A systematic review.

AIMS: Frailty is a complex geriatric syndrome resulting in decreased physiological reserves. Frailty and polypharmacy are common in older adults and the focus of extensive studies, although little is known about the impact they may have on each other. This is the first systematic review analysing the available evidence on the relationship between frailty and polypharmacy in older adults. METHODS: Systematic review of quantitative studies. A comprehensive literature search for publications in English or Spanish was performed on MEDLINE, CINAHL, the Cochrane Database and PsycINFO in September 2017 without applying restrictions on the date of publication. Studies reporting any relationship between frailty and polypharmacy in older adults were considered. RESULTS: A total of 25 publications were included, all of them observational studies. Evaluation of Fried's frailty criteria was the most common approach, followed by the Edmonton Frail Scale and FRAIL scale. Sixteen of 18 cross-sectional analyses and five of seven longitudinal analyses demonstrated a significant association between an increased number of medications and frailty. The causal relationship is unclear and appears to be bidirectional. Our analysis of published data suggests that polypharmacy could be a major contributor to the development of frailty. CONCLUSIONS: A reduction of polypharmacy could be a cautious strategy to prevent and manage frailty. Further research is needed to confirm the possible benefits of reducing polypharmacy in the development, reversion or delay of frailty.