Evidence-based Guideline Update Research Articles

2023 International Evidence-Based Polycystic Ovary Syndrome Guideline Update: Insights From a Systematic Review and Meta-Analysis on Elevated Clinical Cardiovascular Disease in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is the most prevalent female endocrinopathy. Although increased cardiovascular risk factors are well established for the syndrome, PCOS remains overlooked within the realm of cardiology. We conducted a systematic review and meta-analysis on the risk of clinical cardiovascular disease (CVD) events in women with PCOS to inform the 2023 International Evidence-Based PCOS Guideline. A systematic review and meta-analysis was conducted comparing the risk of clinical CVD events in women with and without PCOS. Medline (Ovid), PsycInfo (Ovid), EMBASE, All EBM (Ovid), and CINAHL were searched from January 1, 2017, until March 1, 2023, to update the 2018 PCOS Guideline. Pooled odds ratios (ORs), incidence rate ratios (IRRs), and hazard ratios (HRs) were calculated. Twenty studies involving 1.06 million women (369 317 with PCOS and 692 963 without PCOS) were included. PCOS was associated with higher risk of composite CVD (OR, 1.68 [95% CI, 1.26-2.23]; I2 = 71.0%), composite ischemic heart disease (OR, 1.48 [95% CI, 1.07-2.05]; I2 = 81.0%), myocardial infarction (OR, 2.50 [95% CI, 1.43-4.38]; I2 = 83.3%), and stroke (OR, 1.71 [95% CI, 1.20-2.44]; I2 = 81.4%). The relationship with cardiovascular mortality was less clear (OR, 1.19 [95% CI, 0.53-2.69]; I2 = 0%). Meta-analyses of IRRs support these findings. Results from pooled HRs were limited by the small number of studies and significant heterogeneity. This review provides evidence and highlights the importance of recognizing PCOS as a significant risk factor for CVD morbidity. The 2023 International Evidence-Based PCOS Guideline now recommends awareness of increased CVD risk and comprehensive risk assessment in PCOS to help mitigate the burden of CVD in this common and high-risk condition.

2024 RECOVER Guidelines: Updated treatment recommendations for CPR in dogs and cats.

After the 2012 Reassessment Campaign on Veterinary Resuscitation (RECOVER) CPR Guidelines, this is an update of evidence-based consensus guidelines for Basic Life Support (BLS), advanced life support (ALS), and periarrest monitoring. These RECOVER CPR Guidelines were generated using a modified version of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system for evidence evaluation and translation of this evidence into clear and actionable clinical instructions. Prioritized clinical questions in the Population, Intervention, Comparator, and Outcome (PICO) format were used as the basis to conduct systematic literature searches by information specialists, to extract information from relevant publications, to assess this evidence for quality, and finally to translate the findings into treatment recommendations. These recommendations were reviewed by the RECOVER writing group and opened for comment by veterinary professionals for 4weeks. Transdisciplinary, international collaboration in university, specialty, and emergency practice. A total of 40 worksheets were prepared to evaluate questions across the 3 domains of BLS, ALS and Monitoring, resulting in 90 individual treatment recommendations. High-dose epinephrine is no longer recommended, and atropine, if used, is only administered once. Bag-mask ventilation is prioritized over mouth-to-nose ventilation in nonintubated animals. In addition, an algorithm for initial assessment, an updated CPR algorithm, a rhythm diagnosis tool, and an updated drug dosing table are provided. While the majority of the BLS and ALS recommendations remain unchanged, some noteworthy changes were made due to new evidence that emerged over the past 10years. Indirectness of evidence remains the largest impediment to the certainty of guidelines formulation and underscores an urgent need for more studies in the target species of dogs and cats.

Utility of Serum Anti-Müllerian Hormone Measurement as Part of Polycystic Ovary Syndrome Diagnosis.

The 2023 international evidence-based guideline update for the assessment and management of polycystic ovary syndrome (PCOS) recommends using the Rotterdam criteria for the diagnosis of PCOS. The updated guideline has evidence-based recommendation for the diagnosis, and it now also includes serum anti-Müllerian hormone (AMH) measurement as an alternative tool for gynecological ultrasound to diagnose polycystic ovary morphology (PCOM). The aim of this new recommendation was to facilitate PCOS diagnostic workup in primary care and other disciplines, as currently most diagnosing is done in gynecology and infertility clinics. Here, we review factors affecting AMH levels as well as the utility of AMH in PCOS diagnosis. We identified relevant studies that report different cut-offs for AMH to diagnose PCOM as part of PCOS diagnosis. There are, however, some limitations when using AMH that should be acknowledged. These include physiological aspects like age, ethnicity, and obesity and iatrogenic causes like hormonal medication and ovarian surgery. Also reference ranges are different depending on AMH assay used. As a summary, we conclude that AMH is a usable tool in PCOM diagnostics, but it does not have a single cut-off. Therefore, further studies are needed to establish age and assay-based reference ranges.

Recommendations From the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome.

Recommendations From the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome.

Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome†.

Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome†.

Continuing, reducing, switching, or stopping antipsychotics in individuals with schizophrenia-spectrum disorders who are clinically stable: a systematic review and network meta-analysis

Although antipsychotic maintenance treatment is widely recommended to prevent relapse in chronic psychoses, evidence-based guidelines do not provide clear indications on different maintenance treatment strategies, including continuing the antipsychotic at standard doses, reducing the dose, switching to another antipsychotic, or even stopping the antipsychotic. We aimed to compare the effectiveness of these maintenance treatment strategies, hypothesising the superiority of all strategies over stopping, and of continuing at standard doses over both switching and reducing the dose. We did a systematic review and network meta-analysis of randomized controlled trials (RCTs) that investigated antipsychotics for relapse prevention in adults with schizophrenia-spectrum disorders who were clinically stable, and which compared four treatment strategies: continuing the current antipsychotic at standard doses recommended for acute treatment; reducing the current antipsychotic dose; switching to a different antipsychotic; and stopping the antipsychotic and replacing it with placebo. We excluded RCTs with fewer than 25 individuals, a prerandomisation washout period greater than 4 weeks, a follow-up shorter than 6 weeks, and those recruiting treatment-resistant individuals. We searched MEDLINE, EMBASE, PsycINFO, CINAHL, CENTRAL, and online trial registers for published and unpublished RCTs from inception to Sept 1, 2021, combining terms describing all available antipsychotics, and terms describing continuation, maintenance, or long-term treatment for schizophrenia-spectrum disorders. Relative risks (RRs) and standardised mean differences were pooled using random-effects pairwise and network meta-analyses. We assessed risk of bias of each RCT with the Cochrane Risk-of-Bias 2 tool, and confidence of pooled estimates with CINeMA. The primary outcome was relapse prevention. The study protocol was registered in advance in the Open Science Forum registry. Of 3936 records identified, 119 records, reporting on 101 RCTs, were eligible, 98 of which (including 13 988 individuals) provided data that could be meta-analysed for at least one outcome. The mean proportion of female participants per study was 38% (range 0-100; median 39%, IQR 29-50), whereas for male participants it was 62% (range 0-100; median 61%, IQR 50-71), and the overall mean age was 38·8 years (range 23·2-63·9; median 39·3, IQR 35·0-43·9). Of the 98 RCTs meta-analysed, 89·8% were done in high-income and upper-middle-income countries. The ethnic group White or so-called Caucasian was the most represented (mean 56% participants per study), although this information was relatively scarce. All continuation strategies were significantly more effective in preventing relapse than stopping antipsychotic treatment, with a large risk reduction for continuing at standard doses (RR 0·37, 95% CI 0·32-0·43; number-needed-to-treat [NNT] 3·17, 95% CI 2·94-3·51) and antipsychotic switching (RR 0·44, 0·37-0·53; NNT 3·57, 3·17-4·25), and moderate risk reduction for dose reduction (RR 0·68, 0·51-0·90; NNT 6·25, 4·08-20·00). Continuing and switching antipsychotics did not differ significantly (RR 0·84, 0·69-1·02; with lower values favouring continuing), whereas reducing antipsychotic dose was outperformed by both continuing (RR 0·55, 0·42-0·71; NNT 4·44, 3·45-6·90) and switching (RR 0·65, 0·47-0·89; NNT 5·17, 3·77-18·18). Results were supported by moderate confidence of evidence and confirmed by secondary analyses and by several sensitivity and subgroup analyses, including removing studies with abrupt antipsychotic discontinuation or fast tapering (≤4 weeks). No tolerability differences emerged between treatment strategies. According to the Cochrane Risk-of-Bias tool, version 2, 16·8% of included RCTs had an overall high risk of bias for the primary outcome. We found moderate heterogeneity (τ2=0·13; I2=61%) and no overall incoherence for the primary analysis. Results were supported by moderate confidence of evidence and confirmed by secondary analyses. Contrary to our original hypothesis, we found that continuing antipsychotic treatment at standard doses or switching to a different antipsychotic are similarly effective treatment strategies, whereas reducing antipsychotic doses below standard doses is associated with higher risk of relapse than the other two maintenance treatment strategies and should therefore be limited to selected cases. Despite limitations, including moderate heterogeneity and moderate certainty of evidence, these results are of pragmatic relevance for clinicians, and should support the update of evidence-based guidelines. None.

Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of neuropathology in the management of progressive glioblastoma in adults.

These recommendations apply to adult patients with progressive or recurrent glioblastoma (GBM). For adult patients with progressive glioblastoma does testing for Isocitrate Dehydrogenase (IDH) 1 or 2 mutations provide new additional management or prognostic information beyond that derived from the tumor at initial presentation? Level III: Repeat IDH mutation testing is not necessary if the tumor is histologically similar to the primary tumor and the patient's clinical course is as expected. For adult patients with progressive glioblastoma does repeat testing for MGMT promoter methylation provide new or additional management or prognostic information beyond that derived from the tumor at initial presentation and what methods of detection are optimal? Level III: Repeat MGMT promoter methylation is not recommended. For adult patients with progressive glioblastoma does EGFR amplification or mutation testing provide management or prognostic information beyond that provided by histologic analysis and if performed on previous tissue samples, does it need to be repeated? Level III: In cases that are difficult to classify as glioblastoma on histologic features EGFR amplification testing may help in classification. If a previous EGFR amplification was detected, repeat testing is not necessary. Repeat EGFR amplification or mutational testing may be recommended in patients in which target therapy is being considered. For adult patients with progressive glioblastoma does large panel or whole genome sequencing provide management or prognostic information beyond that derived from histologic analysis? Level III: Primary or repeat large panel or whole genome sequencing may be considered in patients who are eligible or interested in molecularly guided therapy or clinical trials. For adult patients with progressive glioblastoma should immune checkpoint biomarker testing be performed to provide management and prognostic information beyond that obtained from histologic analysis? Level III: The current evidence does not support making PD-L1 or mismatch repair (MMR) enzyme activity a component of standard testing. For adult patients with progressive glioblastoma are there meaningful biomarkers for bevacizumab responsiveness and does their assessment provide additional information for tumor management and prognosis beyond that learned by standard histologic analysis? Level III: No established Bevacizumab biomarkers are currently available based upon the inclusion criteria of this guideline.

Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of cytoreductive surgery in the management of progressive glioblastoma in adults.

In patients with previously diagnosed glioblastoma who are suspected of experiencing progression, does repeat cytoreductive surgery improve progression free survival or overall survival compared to alternative interventions? These recommendations apply to adults with previously diagnosed glioblastoma who are suspected of experiencing progression of the neoplastic process and are amenable to surgical resection. Level II: Repeat cytoreductive surgery is recommended in progressive glioblastoma patients to improve overall survival.

Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of cytotoxic chemotherapy and other cytotoxic therapies in the management of progressive glioblastoma in adults.

These recommendations apply to adult patients diagnosed with progressive glioblastoma (pGBM). QUESTION (Q1): In adult patients with pGBM does the use of temozolomide (TMZ) with alternative dosing or the use of TMZ in combination with other cytotoxic treatments result in increased overall survival compared to other chemotherapy? Level III: Adult patients with pGBM might derive benefit in treatment with TMZ, especially those who progress after more than 5months of TMZ-treatment free interval. Combination of TMZ with other cytotoxic agents such as nitrosourea, cisplatin, electrohyperthermia, or tamoxifen is not suggested in adult patients with pGBM as a stand-alone therapy. There is insufficient data to make a recommendation about which alternative TMZ dosing provides the best benefits. QUESTION (Q2): In adult patients with pGBM does the use of systemic or in situ nitrosourea result in increased overall survival compared to other chemotherapy? Level III: In the setting of pGBM, fotemustine is suggested in elderly patients with methylated MGMT promoter status. There is insufficient evidence to compare fotemustine to other nitrosoureas. There is insufficient evidence to make a recommendation about the use of in situ nitrosourea in patients with pGBM who underwent the Stupp regimen. QUESTION (Q3): In adult patients with pGBM does the use of platinum compounds and topoisomerase result in increased survival compared to other chemotherapy? Level III: Other chemotherapy including platinum compounds and topoisomerase inhibitors are not suggested to be used in adult patients with pGBM. Other cytotoxic therapies like perillyl acohol or ketogenic diet are not suggested for use in adult patients with pGBM as a stand-alone therapy. QUESTION (Q4): In adult patients with pGBM does the use of tumor treating field (TTF) result in increased overall survival compared to chemotherapy? Level III: The use of TTF with other chemotherapy may be considered when treating adult patients with pGBM. There is insufficient evidence to recommend TTF to increase overall survival in adult patients with pGBM. QUESTION (Q5): In adult patients with pGBM does the use of oncolytic virotherapy result in increased survival compared to chemotherapy? Level III: Oncolytic virotherapy is not suggested in patients with pGBM.

Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of radiation therapy in the management of progressive and recurrent glioblastoma in adults.

These recommendations apply to adult patients (18years of age and above) with progressive/recurrent glioblastoma multiforme (pGBM) after first line combined multimodality treatment. Can re-irradiation (by using conventional radiotherapy, fractionated radiosurgery, or single fraction radiosurgery) be used in patients with pGBM after the first adjuvant combined multimodality treatment with radiation and chemotherapy? Level III: When the target tumor is amenable for additional radiation, re-irradiation is recommended as it provides improved local tumor control, as measured by best imaging response. Such re-irradiation can take the form of conventional fractionation radiotherapy, fractionated radiosurgery, or single fraction radiosurgery. Re-Irradiation is recommended in order to maintain or improve a patient's neurological status and quality of life prior to any further tumor progression.

Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of imaging in the management of progressive glioblastoma in adults.

These recommendations apply to adults with glioblastoma who have been previously treated with first-line radiation or chemoradiotherapy and who are suspected of experiencing tumor progression. In patients with previously treated glioblastoma, is standard contrast-enhanced magnetic resonance imaging including diffusion weighted imaging useful for diagnosing tumor progression and differentiating progression from treatment-related changes? Magnetic resonance imaging with and without gadolinium enhancement including diffusion weighted imaging is recommended as the imaging surveillance method to detect the progression of previously diagnosed glioblastoma. In patients with previously treated glioblastoma, does magnetic resonance spectroscopy add useful information for diagnosing tumor progression and differentiating progression from treatment-related changes beyond that derived from standard magnetic resonance imaging with and without gadolinium enhancement? Magnetic resonance spectroscopy is recommended as a diagnostic method to differentiate true tumor progression from treatment-related imaging changes or pseudo-progression in patients with suspected progressive glioblastoma. In patients with previously treated glioblastoma, does magnetic resonance perfusion add useful information for diagnosing tumor progression and differentiating progression from treatment-related changes beyond that derived from standard magnetic resonance imaging with and without gadolinium enhancement? Magnetic resonance perfusion is suggested as a diagnostic method to differentiate true tumor progression from treatment-related imaging changes or pseudo-progression in patients with suspected progressive glioblastoma. In patients with previously treated glioblastoma, does the addition of single-photon emission computed tomography (SPECT) provide additional useful information for diagnosing tumor progression and differentiating progression from treatment-related changes beyond that derived from standard magnetic resonance imaging with and without gadolinium enhancement? Single-photon emission computed tomography imaging is suggested as a diagnostic method to differentiate true tumor progression from treatment-related imaging changes or pseudo-progression in patients with suspected progressive glioblastoma. In patients with previously treated glioblastoma, does 18F-fluorodeoxyglucose positron emission tomography add useful information for diagnosing tumor progression and differentiating progression from treatment-related changes beyond that derived from standard magnetic resonance imaging with and without gadolinium enhancement? The routine use of 18F-fluorodeoxyglucose positron emission tomography to identify progression of glioblastoma is not recommended. In patients with previously treated glioblastoma, does positron emission tomography with amino acid agents add useful information for diagnosing tumor progression and differentiating progression from treatment-related changes beyond that derived from standard magnetic resonance imaging with and without gadolinium enhancement? It is suggested that amino acid positron emission tomography be considered to assist in the differentiation of progressive glioblastoma from treatment related changes.

Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of targeted therapies and immunotherapies in the management of progressive glioblastoma.

The following questions and recommendations are pertinent to the following:Target populationThese recommendations apply to adults with progressive GBM who have undergone standard primary treatment with surgery and/or chemoradiation.Question 1In adults with progressive glioblastoma is the use of bevacizumab as monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RecommendationLevel III: Treatment with bevacizumab is suggested in the treatment of progressive GBM, as it provides improved disease control compared to historical controls as measured by best imaging response and progression free survival at 6 months, while not providing evidence for improvement in overall survival.Question 2In adults with progressive glioblastoma is the use of bevacizumab as combination therapy with cytotoxic agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RecommendationLevel III: There is insufficient evidence to show benefit or harm of bevacizumab in combination with cytotoxic therapies in progressive glioblastoma due to a lack of evidence supporting a clearly defined benefit without significant toxicity.Question 3In adults with progressive glioblastoma is the use of bevacizumab as a combination therapy with targeted agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RecommendationThere is insufficient evidence to support a recommendation regarding this question.Question 4In adults with progressive glioblastoma is the use of targeted agents as monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RecommendationThere is insufficient evidence to support a recommendation regarding this question.Question 5In adults with progressive glioblastoma is the use of targeted agents in combination with cytotoxic therapies superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RecommendationThere is insufficient evidence to support a recommendation regarding this question.Question 6In adults with progressive glioblastoma is the use of immunotherapy monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RecommendationThere is insufficient evidence to support a recommendation regarding this question.Question 7In adults with progressive glioblastoma is the use of immunotherapy in combination with targeted agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RecommendationThere is insufficient evidence to support a recommendation regarding this question.Question 8In adults with progressive glioblastoma is the use of immunotherapy in combination with bevacizumab superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RecommendationThere is insufficient evidence to support a recommendation regarding this question.

PCOS Phenotype in Unselected Populations Study (P-PUP): Protocol for a Systematic Review and Defining PCOS Diagnostic Features with Pooled Individual Participant Data.

The diagnosis of polycystic ovary syndrome (PCOS) remains challenging due to limited data regarding normative cut-offs for the diagnostic features in different subpopulations. We aim to conduct a systematic review, build a comprehensive repository of de-identified individual participant data (IPD), and define normative ranges and diagnostic cut-offs for all PCOS diagnostic features. We will conduct a systematic search of MEDLINE and EMBASE databases for studies that assessed PCOS diagnostic features in unselected women. Two reviewers will assess eligibility and perform quality appraisal. Authors of included studies will be invited to contribute IPD. Primary variables include directly assessed modified Ferriman Gallwey (mFG) scores; menstrual cycle lengths; follicle number per ovary (FNPO), ovarian volume (OV), anti-Müllerian hormone (AMH); circulating androgens, including total testosterone (TT), free testosterone, bioavailable testosterone, free androgen index (FAI), androstenedione (A4), and dehydroepiandrosterone sulphate (DHEAS). Normative ranges and cut-offs will be defined using cluster analysis. Monash University Human Research Ethics Committee granted ethical approval (26938/0 1/12/2020), all IPD will be de-identified and primary studies have ethical approval from their institutional ethics committees. Findings will clarify distinction between PCOS and non-PCOS populations, and inform the update of the international evidence-based guidelines for the assessment and management of PCOS.

Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of emerging developments in the management of newly diagnosed glioblastoma

These recommendations apply to adult patients with newly diagnosed or suspected glioblastoma. Question What imaging modalities are in development that may be able to provide improvements in diagnosis, and therapeutic guidance for individuals with newly diagnosed glioblastoma? Level III: It is suggested that techniques utilizing magnetic resonance imaging for diffusion weighted imaging, and to measure cerebral blood and magnetic spectroscopic resonance imaging of N-acetyl aspartate, choline and the choline to N-acetyl aspartate index to assist in diagnosis and treatment planning in patients with newly diagnosed or suspected glioblastoma. Question What new surgical techniques can be used to provide improved tumor definition and resectability to yield better tumor control and prognosis for individuals with newly diagnosed glioblastoma? Level II: The use of 5-aminolevulinic acid is recommended to improve extent of tumor resection in patients with newly diagnosed glioblastoma. Level II: The use of 5-aminolevulinic acid is recommended to improve median survival and 2 year survival in newly diagnosed glioblastoma patients with clinical characteristics suggesting poor prognosis. Level III: It is suggested that, when available, patients be enrolled in properly designed clinical trials assessing the value of diffusion tensor imaging in improving the safety of patients with newly diagnosed glioblastoma undergoing surgery. Question What new pathology techniques and measurement of biomarkers in tumor tissue can be used to provide improved diagnostic ability, and determination of therapeutic responsiveness and prognosis for patients with newly diagnosed glioblastomas? Level II: Assessment of tumor MGMT promoter methylation status is recommended as a significant predictor of a longer progression free survival and overall survival in patients with newly diagnosed with glioblastoma. Level II: Measurement of tumor expression of neuron-glia-2, neurofilament protein, glutamine synthetase and phosphorylated STAT3 is recommended as a predictor of overall survival in patients with newly diagnosed with glioblastoma. Level III: Assessment of tumor IDH1 mutation status is suggested as a predictor of longer progression free survival and overall survival in patients with newly diagnosed with glioblastoma. Level III: Evaluation of tumor expression of Phosphorylated Mitogen-Activated Protein Kinase protein, EGFR protein, and Insulin-like Growth Factor-Binding Protein-3 is suggested as a predictor of overall survival in patients with newly diagnosed with glioblastoma. Question What radiation therapy techniques are in development that may be used to provide improved tumor control and prognosis for individuals with newly diagnosed glioblastomas? Level III: It is suggested that patients with newly diagnosed glioblastoma undergo pretreatment radio-labeled amino acid tracer positron emission tomography to assess areas at risk for tumor recurrence to assist in radiation treatment planning. Level III: It is suggested that, when available, patients be with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of radiation dose escalation, altered fractionation, or new radiation delivery techniques. Question What emerging chemotherapeutic agents or techniques are available to provide better tumor control and prognosis for patients with newly diagnosed glioblastomas? Level III: As no emerging chemotherapeutic agents or techniques were identified in this review that improved tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of chemotherapy. Question What new targeted therapy agents are available to provide better tumor control and prognosis for individuals with newly diagnosed glioblastomas? Level III: As no new molecular and targeted therapies have clearly provided better tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of molecular and targeted therapies IMMUNOTHERAPY: Question What emerging immunotherapeutic agents or techniques are available to provide better tumor control and prognosis for patients with newly diagnosed glioblastomas? Level III: As no immunotherapeutic agents have clearly provided better tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of immunologically-based therapies. Question What novel therapies or techniques are in development to provide better tumor control and prognosis for individuals with newly diagnosed glioblastomas? Level II: The use of tumor-treating fields is recommended for patients with newly diagnosed glioblastoma who have undergone surgical debulking and completed concurrent chemoradiation without progression of disease at the time of tumor-treating field therapy initiation. Level II: It is suggested that, when available, enrollment in properly designed studies of vector containing herpes simplex thymidine kinase gene and prodrug therapies be considered in patients with newly diagnosed glioblastoma.

Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of chemotherapeutic management and antiangiogenic treatment of newly diagnosed glioblastoma in adults.

What is the role of temozolomide in the management of adult patients (aged 65 and under) with newly diagnosed glioblastoma? These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma. Level I: Concurrent and post-irradiation Temozolomide (TMZ) in combination with radiotherapy and post-radiotherapy as described by Stupp et al. is recommended to improve both PFS and OS in adult patients with newly diagnosed GBM. There is no evidence that alterations in the dosing regimen have additional beneficial effect. Is there benefit to adjuvant temozolomide treatment in elderly patients (> 65years old?). These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma. Level III: Adjuvant TMZ treatment is suggested as a treatment option to improve PFS and OS in adult patients (over 70years of age) with newly diagnosed GBM. What is the role of local regional chemotherapy with BCNU biodegradable polymeric wafers in adult patients with newly diagnosed glioblastoma? These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma. Level III: There is insufficient evidence for the use of BCNU wafers following resection in patients with newly diagnosed glioblastoma who undergo the Stupp protocol after surgery. Further studies of higher quality are suggested to understand the role of BCNU wafer and other locoregional therapy in the setting of Stupp Protocol. What is the role of bevacizumab in the adult patient with newly diagnosed glioblastoma? These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma. Level I: Bevacizumab in general is not recommended in the initial treatment of adult patients with newly diagnosed GBM. It continues to be strongly recommended that patients with newly diagnosed GBM be enrolled in properly designed clinical trials to assess the benefit of novel chemotherapeutic agents compared to standard therapy.

Canadian Society of Nephrology Commentary on the Kidney Disease Improving Global Outcomes 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder.

Purpose of review:(1) To provide commentary on the 2017 update to the Kidney Disease Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD); (2) to apply the evidence-based guideline update for implementation within the Canadian health care system; (3) to provide comment on the care of children with chronic kidney disease (CKD); and (4) to identify research priorities for Canadian patients.Sources of information:The KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD.Methods:The commentary committee co-chairs selected potential members based on their knowledge of the Canadian kidney community, aiming for wide representation from relevant disciplines, academic and community centers, and different geographical regions.Key findings:We agreed with many of the recommendations in the clinical practice guideline on the diagnosis, evaluation, prevention, and treatment of CKD-MBD. However, based on the uncommon occurrence of abnormalities in calcium and phosphate and the low likelihood of severe abnormalities in parathyroid hormone (PTH), we recommend against screening and monitoring levels of calcium, phosphate, PTH, and alkaline phosphatase in adults with CKD G3. We suggest and recommend monitoring these parameters in adults with CKD G4 and G5, respectively. In children, we agree that monitoring for CKD-MBD should begin in CKD G2, but we suggest measuring ionized calcium, rather than total calcium or calcium adjusted for albumin. With regard to vitamin D, we suggest against routine screening for vitamin D deficiency in adults with CKD G3-G5 and G1T-G5T and suggest following population health recommendations for adequate vitamin D intake. We recommend that the measurement and management of bone mineral density (BMD) be according to general population guidelines in CKD G3 and G3T, but we suggest against routine BMD testing in CKD G4-G5, CKD G4T-5T, and in children with CKD. Based on insufficient data, we also recommend against routine bone biopsy in clinical practice for adults with CKD or CKD-T, or in children with CKD, although we consider it an important research tool.Limitations:The committee relied on the evidence summaries produced by KDIGO. The CSN committee did not replicate or update the systematic reviews.

Noninvasive and Wearable Optical Monitoring of Brain Death with Aid of a Protocol at Differentiated Fractions of Oxygen Inspired

Brain death is a permanent loss of all brain function [1]. Current clinical organ transplantations mostly depend on the organs from brain-dead patients [2]. And of note, a lot of blood deases are easy to cause cerebral haemorrhage, which is quite of danger and usually induce brain death if not detected and treated in time. Thus prompt evaluation of brain death is of great significance for saving medical resources and reducing economic burden of the patients' families. Current guide for diagnosing brain death required to perform a list of >30 hours neurological examninations, some of which are even invasive, not in time and easily hampered by many confounding factors. An ideal ancillary test to assess brain death is highlighted to be noninvasive, sensitive, universally available, timely, and easy to perform at the bedside. Near infrared spectroscopy ( NIRS ) is capable of monitoring hemodynamics in response to brain activity noninvasively, conveniently, continually, and relatively inexpensively, evidented by a series of clinical cerebral studies recently. Weigl et al newly reported to use a time resolved NIRS to detect the fluorescence photons excited in the indocyanine green ( ICG ) for cerebral perfusion detection. It provided a novel optical ancillary tool to assess brain death, while its accuracy was only 69.2%, which did not reach the level of brain death confirmation. Plus, it was invasive, requiring injection of optical contrast agent. We attempted to assess brain death completely in nonivasive way with just a custom wearable NIRS device developed in our lab [3] ( fig.1 a ). We novelly incororate a protocol at markedly but safely varied fractions of oxygen respiration. Firstly, Monte Carlo modeling were carried out to test the difference in photon transport within human brain at different oxygen concentrations induced by varied fractions of oxygen respiration ( FIO2 ) [4]. 18 healthy subjects ( 41 ± 11 years old ) and 17 brain dead patients were recruited from the intensive care unit (ICU) in Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital. No significant difference in age was found between patients and healthy groups ( p >0.413 ). These patients were finally clinically diagnosed by the international standards of brain death. Two protocols were used ( fig.1 b). One is consisted of 1 hour resting, 3-minute baseline measure, half-hour measurement at 60% FIO2 ( phase I, high oxygen ),a half hour measure at 40% FIO2 ( phase II, low oxygen ), and a half hour measure at 60% FIO2 ( phase III, high oxygen ). The other is low, high, and low. The Δ[Hb] and Δ[HbO2] time courses were recorded by NIRS in real time with related signal processing ( fig.1 c ). Statistical analysis were focus on the sensitivity and specificiy of our proposed methodology at combination of NIRS and above protocol, as well as which protocol act better. Fig.1 ( c right ) showed that the detected light signal profile dramatically differed among varied oxygen concentrations in human brain. Plus the hemodynamic responses varied clearly between two subject groups among varied FIO2 in both protocols ( fig1. d ). The ' II-III ' phase act more distinct in differing two groups than ' I-II ' phase. And the low-high-low protocol acted almost perfect in accessing brain death with highest sensitivity and specificity. Over all, the novel incorporation of NIRS and a low-high-low varied FIO2 protocol was shown to a be most sensitive, highly specific, noninvasive and real time way to assess brain death and promptly offer quality assured donor organs. [1] E. F. M. Wijdicks, P. N. Varelas, G. S. Gronseth, D. M. Greer, Evidence-based guideline update: Determining brain death in adults report of the quality standards subcommittee of the American Academy of Neurology, Neurology, vol. 74, no. 23, pp. 1911-1918, 2010 [2] K. Singbartl, R. Murugan, A. M. Kaynar, D. W. Crippen, S. A. Tisherman, K. Shutterly, S. A. Stuart, R. Simmons, Intensivist-led management of brain-dead donors is associated with an increase in organ recovery for transplantation, J. M. Darby, Am. J. Transplant., vol. 11, no. 7, pp. 1517-1521, 2011 [3] T. Li, M. Duan, Y. Zhao, G. Yu, Z. Ruan. Bedside monitoring of patients with shock using a portable spatially-resolved near-infrared spectroscopy. Biomed. Opt. Express, vol. 6, no. 9, pp. 3431-3436, 2015 [4] B. Pan, C. Huang, X. Fang, X. Huang, T. Li*, Noninvasive and Sensitive Optical Assessment of Brain Death, J. Biophotonics, vol. 12, no. 3, pp. e201800240, 2018 Disclosures No relevant conflicts of interest to declare.

ESPEN guideline on clinical nutrition in liver disease

This update of evidence-based guidelines (GL) aims to translate current evidence and expert opinion into recommendations for multidisciplinary teams responsible for the optimal nutritional and metabolic management of adult patients with liver disease. The GL was commissioned and financially supported by ESPEN. Members of the guideline group were selected by ESPEN. We searched for meta-analyses, systematic reviews and single clinical trials based on clinical questions according to the PICO format. The evidence was evaluated and used to develop clinical recommendations implementing the SIGN method. A total of 85 recommendations were made for the nutritional and metabolic management of patients with acute liver failure, severe alcoholic steatohepatitis, non-alcoholic fatty liver disease, liver cirrhosis, liver surgery and transplantation as well as nutrition associated liver injury distinct from fatty liver disease. The recommendations are preceded by statements covering current knowledge of the underlying pathophysiology and pathobiochemistry as well as pertinent methods for the assessment of nutritional status and body composition.

Laparoscopic ventral/incisional hernia repair: updated Consensus Development Conference based guidelines [corrected

The Executive board of the Italian Society for Endoscopic Surgery (SICE) promoted an update of the first evidence-based Italian Consensus Conference Guidelines 2010 because a large amount of literature has been published in the last 4 years about the topics examined and new relevant issues. The scientific committee selected the topics to be addressed: indications to surgical treatment including special conditions (obesity, cirrhosis, diastasis recti abdominis, acute presentation); safety and outcome of intraperitoneal meshes (synthetic and biologic); fixing devices (absorbable/non-absorbable); abdominal border and parastomal hernia; intraoperative and perioperative complications; and recurrent ventral/incisional hernia. All the recommendations are the result of a careful and complete literature review examined with autonomous judgment by the entire panel. The process was supervised by experts in methodology and epidemiology from the most qualified Italian institution. Two external reviewers were designed by the EAES and EHS to guarantee the most objective, transparent, and reliable work. The Oxford hierarchy (OCEBM Levels of Evidence Working Group*. "The Oxford 2011 Levels of Evidence") was used by the panel to grade clinical outcomes according to levels of evidence. The recommendations were based on the grading system suggested by the GRADE working group. The availability of recent level 1 evidence (a meta-analysis of 10 RCTs) allowed to recommend that not only laparoscopic repair is an acceptable alternative to the open repair, but also it is advantageous in terms of shorter hospital stay and wound infection rate. This conclusion appears to be extremely relevant in a clinical setting. Indications about specific conditions could also be issued: laparoscopy is recommended for the treatment of recurrent ventral hernias and obese patients, while it is a potential option for compensated cirrhotic and childbearing-age female patients. Many relevant and controversial topics were thoroughly examined by this consensus conference for the first time. Among them are the issue of safety of the intraperitoneal mesh placement, traditionally considered a major drawback of the laparoscopic technique, the role for the biologic meshes, and various aspects of the laparoscopic approach for particular locations of the defect such as the abdominal border or parastomal hernias.

What is the latest evidence for nutritional management of patients undergoing treatment for cancer?

s / Journal of Nutrition & Intermediary Metabolism 1 (2014) 1e55 2 the more common cancers and contributed data to studies of less common cancers. While many associations evaluated were not strong our findings contribute to the overall evidence on which national and international recommendations are based. We have also added to the understanding of associations between diet and cancer by examining differences in associations between different cancer subgroups, such as by aggressiveness for prostate cancer or hormone receptor subtype for breast cancer. One area where reasonably consistent associations were found was for measures of body size. On the basis of this a TV campaign promoting waist circumferences of under 100 cm for men and 85 cm for women (6) was developed. New topics of research in this area include studies we are undertaking investigating whether DNA methylation in peripheral blood can predict cancer risk, and whether methylation could be a mechanism linking diet with cancer. We are also working with colleagues in the US to look at associations between a dietary inflammatory score and different cancer outcomes. Despite what we already know, the recent Australian Health Survey (7) indicates that Australians are not following recommendations that could help reduce cancer risk. Among people aged 18 years or older, 63% were obese or overweight, 48% met the Australian guidelines for fruit consumption (2 or more serves per day for adults), 8% met the guidelines for vegetable consumption (5 or more serves per day), around 20% consumed more than 2 standard drinks per day and 67% of those aged 15 years or older were sedentary or performed only a low level of exercise. Further research may refine recommendations and understanding of mechanisms bywhich diet canmodify cancer risk, but epidemiologists need toworkwith others to bring the benefits of this to the population in general. Funding source(s): NHMRC.