The glioblastoma multiforme tumor site promotes the commitment of tumor-infiltrating lymphocytes to the TH17 lineage in humans.

Although glioblastoma multiforme (GBM) is not an invariably cold tumor, checkpoint inhibition has largely failed in GBM. In order to investigate T cell-intrinsic properties that contribute to the resistance of GBM to endogenous or therapeutically enhanced adaptive immune responses, we sorted CD4+ and CD8+ T cells from the peripheral blood, normal-appearing brain tissue, and tumor bed of nine treatment-naive patients with GBM. Bulk RNA sequencing of highly pure T cell populations from these different compartments was used to obtain deep transcriptomes of tumor-infiltrating T cells (TILs). While the transcriptome of CD8+ TILs suggested that they were partly locked in a dysfunctional state, CD4+ TILs showed a robust commitment to the type 17 T helper cell (TH17) lineage, which was corroborated by flow cytometry in four additional GBM cases. Therefore, our study illustrates that the brain tumor environment in GBM might instruct TH17 commitment of infiltrating T helper cells. Whether these properties of CD4+ TILs facilitate a tumor-promoting milieu and thus could be a target for adjuvant anti-TH17 cell interventions needs to be further investigated.

Schwannomas of the greater superficial petrosal nerve - case series, discussion of surgical techniques, and review of literature.

BACKGROUND: Facial nerve schwannomas account for about 0.8% of all petrous mass lesions. Schwannomas of the greater superficial petrosal nerve (GSPN) are a rare subtype with few case-reports up to date. CASE PRESENTATIONS: A retrospective analysis of clinical outcomes, radiographic findings and postoperative complication between June 2007 and December 2020 was performed. Four cases of GSPN schwannomas were reported. The presenting symptoms were facial nerve palsy and hearing loss. Imaging studies showed a subtemporal mass on the anterosuperior aspect of the petrous bone, in one case with extraordinary petrous bone and mastoid infiltration and destruction. Three cases were removed through a subtemporal extra- or intradural approach, one case via a combined pre- and retrosigmoid approach. Improvement of facial nerve palsy occurred in one case; new hearing loss was observed in another case. Xeropthalmia was a short-term temporary deficit in three cases. Short- to mid-term follow-up of the patients has not shown any tumor recurrence. CONCLUSIONS: GSPN schwannomas are rare entities presenting with heterogenous symptoms. Our surgical findings emphasize safe resection. Complete remission is possible by GTR. Since the small data set limits the expressiveness of statements regarding standard of care and alternative therapy options, additional data is needed.

Age-adjusted Charlson comorbidity index in recurrent glioblastoma: a new prognostic factor?

BACKGROUND: For recurrent glioblastoma (GB) patients, several therapy options have been established over the last years such as more aggressive surgery, re-irradiation or chemotherapy. Age and the Karnofsky Performance Status Scale (KPSS) are used to make decisions for these patients as these are established as prognostic factors in the initial diagnosis of GB. This study's aim was to evaluate preoperative patient comorbidities by using the age-adjusted Charlson Comorbidity Index (ACCI) as a prognostic factor for recurrent GB patients. METHODS: In this retrospective analysis we could include 123 patients with surgery for primary recurrence of GB from January 2007 until December 2016 (43 females, 80 males, mean age 57 years (range 21-80 years)). Preoperative age, sex, ACCI, KPSS and adjuvant treatment regimes were recorded for each patient. Extent of resection (EOR) was recorded as a complete/incomplete resection of the contrast-enhancing tumor part. RESULTS: Median overall survival (OS) was 9.0 months (95% CI 7.1-10.9 months) after first re-resection. Preoperative KPSS > 80% (P < 0.001) and EOR (P = 0.013) were associated with significantly improved survival in univariate analysis. Including these factors in multivariate analysis, preoperative KPSS < 80 (HR 2.002 [95% CI: 1.246-3.216], P = 0.004) and EOR are the only significant prognostic factor (HR 1.611 [95% CI: 1.036-2.505], P = 0.034). ACCI was not shown as a prognostic factor in univariate and multivariate analyses. CONCLUSION: For patients with surgery for recurrent glioblastoma, the ACCI does not add further information about patient's prognosis besides the well-established KPSS and extent of resection.

Prognostic value of tumour volume in patients with a poor Karnofsky performance status scale - a bicentric retrospective study.

BACKROUND: Median overall survival (OS) after diagnosis of glioblastoma (GBM) remains 15 months amongst patients receiving aggressive surgical resection, chemotherapy and irradiation. Treatment of patients with a poor preoperative Karnofsky Performance Status Scale (KPSS) is still controversial. Therefore, we retrospectively assessed the outcome after surgical treatment in patients with a KPSS of ≤60%. METHODS: We retrospectively included patients with a de-novo glioblastoma WHO °IV and preoperative KPSS ≤60%, who underwent surgery at two neurosurgical centres between September 2006 and March 2016. We recorded pre- and postoperative tumour volume, pre- and postoperative KPSS, OS, age and MGMT promoter status. RESULTS: One hundred twenty-three patients (58 females/65 males, mean age 67.4 ± 13.4 years) met the inclusion criteria. Seventy-five of the 123 patients (61%) underwent surgical resection. 48/123 patients (39%) received a biopsy. The median preoperative and postoperative tumour volume of all patients was 33.0 ± 31.3 cm3 (IR 15.0-56.5cm3) and 3.1 ± 23.8 cm3 (IR 0.2-15.0 cm3), respectively. The median KPSS was 60% (range 20-60%) preoperatively and 50% (range 0-80%) postoperatively. Patients who received a biopsy showed a median OS for patients who received a biopsy only was 3.0 months (95% CI 2.0-4.0 months), compared to patients who had a resection and had a median OS of 8 months (95% CI 3.1-12.9 months). Age (p < 0.001, HR: 1.045 [95% CI 1.022-1.068]), postoperative tumour volume (p = 0.02, HR: 1.016 [95% CI 1.002-1.029]) and MGMT promotor status (p = 0.016, HR: 0.473 [95% CI 0.257-0.871]) were statistically significant in multivariate analysis. In subgroup analyses only age was shown as a significant prognostic factor in multivariate analyses for patients receiving surgery (p < 0.001, HR: 1.046 [95% CI 1.022-1.072]). In the biopsy group no significant prognostic factors were shown in multivariate analysis. CONCLUSION: GBM patients with a preoperative KPSS of ≤60% might profit from surgical reduction of tumour burden.

The interhemispheric fissure-surgical outcome of interhemispheric approaches.

Exposure of the anterior skull base is challenging due to strategic structures. The interhemispheric approach (IHA) has turned out to be a feasible technique. We report our experience with IHAs in patients with extraaxial lesions (EAL). We performed a retrospective chart review at a tertiary neurosurgical center between April 2009 and March 2020. We included patients with resection of EAL through IHAs concentrating on surgical technique, complete resection rate, postoperative outcome, and complications. Seventy-four patients resected by an IHA were included: 49 (66.2%) frontal (FIA), nine (12.1%) parietooccipital (PIA), and 16 (21.6%) frontobasal IHAs (FBIAs). Median age at time of surgery was 59 years (range 16-88 years), 47 (63.5%) female and 27 (36.5%) male. Complete resection rate was 83.8% (FIA 89.8%, PIA 55.6%, FBIA 81.3%). Rate of new minor deficits was 17.6%, rate of major deficits 5.4%, total rate 23.0%. 51 (68.9%) WHO°I meningiomas, ten (13.5%) WHO°II meningiomas, two (2.7%) WHO°III meningiomas, nine (12.2%) metastases, one (1.4%) sarcoma, and one (1.4%) local adenocarcinoma were resected. Total complication rate was 27.0%. Rate of major complications requiring intervention was 9.6%. Mean follow-up was 34.2 (± 33.2) months. In patients with lesions of the interhemispheric fissure, overall morbidity and complications are comparatively high. Extensions of IHAs with potential even higher morbidity are not necessary though; we support the use of standardized IHAs. Our findings suggest regular usage of relatively feasible IHAs for a satisfying outcome. Invasive, complicated, or contralateral trajectories were not needed.

Minimally invasive posterior pedicle screw fixation versus open instrumentation in patients with thoracolumbar spondylodiscitis.

BACKGROUND: Due to the aging society, the incidence of pyogenic spondylodiscitis is still rising. Although surgical treatment for spondylodiscitis in general is increasingly accepted, an optimal surgical strategy for treatment of pyogenic spinal infection has not yet been established. The aim of this study was to investigate the suitability of percutaneous posterior pedicle screw fixation for surgical treatment in patients with spondylodiscitis of the thoracolumbar spine. METHODS: We conducted a retrospective review of a consecutive cohort of patients undergoing surgical treatment for spondylodiscitis of the thoracolumbar spine between January 2017 and December 2019. We assessed intraoperative and clinical data, comparing for the classic open and the percutaneous approach. In total, we analyzed 125 cases (39 female, 86 male). The mean age was 69.49 years ± 12.63 years. RESULTS: Forty-seven (37.6%) patients were operated on by a percutaneous approach for pedicle screw fixation, and 78 (62.4%) received open surgery. There was no significant difference in the mean age of patients between both groups (p= 0.57). The time of surgery for percutaneous fixation was statistically significantly shorter (p= 0.03). Furthermore, the estimated intraoperative blood loss was significantly lower in the minimally invasive group (p < 0.001). No significant difference could be observed regarding the recurrence rate of spondylodiscitis and the occurrence of surgical site infections (p= 0.2 and 0.5, respectively). CONCLUSION: Percutaneous posterior pedicle screw fixation appears to be a feasible option for the surgical treatment of a selected patient group with spondylodiscitis of the thoracic and lumbar spine.

Milk polar lipids reduce lipid cardiovascular risk factors in overweight postmenopausal women: towards a gut sphingomyelin-cholesterol interplay.

OBJECTIVE: To investigate whether milk polar lipids (PL) impact human intestinal lipid absorption, metabolism, microbiota and associated markers of cardiometabolic health. DESIGN: A double-blind, randomised controlled 4-week study involving 58 postmenopausal women was used to assess the chronic effects of milk PL consumption (0, 3 or 5 g-PL/day) on lipid metabolism and gut microbiota. The acute effects of milk PL on intestinal absorption and metabolism of cholesterol were assessed in a randomised controlled crossover study using tracers in ileostomy patients. RESULTS: Over 4 weeks, milk PL significantly reduced fasting and postprandial plasma concentrations of cholesterol and surrogate lipid markers of cardiovascular disease risk, including total/high-density lipoprotein-cholesterol and apolipoprotein (Apo)B/ApoA1 ratios. The highest PL dose preferentially induced a decreased number of intestine-derived chylomicron particles. Also, milk PL increased faecal loss of coprostanol, a gut-derived metabolite of cholesterol, but major bacterial populations and faecal short-chain fatty acids were not affected by milk PL, regardless of the dose. Acute ingestion of milk PL by ileostomy patients shows that milk PL decreased cholesterol absorption and increased cholesterol-ileal efflux, which can be explained by the observed co-excretion with milk sphingomyelin in the gut. CONCLUSION: The present data demonstrate for the first time in humans that milk PL can improve the cardiometabolic health by decreasing several lipid cardiovascular markers, notably through a reduced intestinal cholesterol absorption involving specific interactions in the gut, without disturbing the major bacterial phyla of gut microbiota. TRIAL REGISTRATION NUMBER: NCT02099032 and NCT02146339; Results.

Dietary lipids and cardiometabolic health: a new vision of structure-activity relationship.

PURPOSE OF REVIEW: The impact of dietary lipids on cardiometabolic health was mainly studied considering their fatty acid composition. This review aims to present the recent change in paradigm whereby the food matrix, the molecular and supramolecular structures of dietary lipids modulate their digestive fate and cardiometabolic impact. RECENT FINDINGS: Epidemiological studies have reported that the metabolic impact of full-fat dairy products is better than predictable upon saturated fatty acid richness. Milk polar lipid supplementation reduced adiposity and inflammation in rodents by modulating gut microbiota and barrier, and decreased lipid markers of cardiovascular disease risk in humans by lowering cholesterol absorption. The metabolic importance of the structure of lipid molecules carrying omega-3 (molecular carrier) has also been documented. Plant lipids exhibit specific assemblies, membrane and molecular structures with potential health benefits. Lipid emulsifiers used to stabilize fats in processed foods are not mere bystanders of lipid effects and can induce both beneficial and adverse health effects. SUMMARY: These findings open new clinical research questions aiming to further characterize the cardiometabolic fate of lipids, from digestion to bioactive metabolites, according to the food source or molecular carrier. This should be useful to elaborate food formulations for target populations and personalized dietary recommendations.

Intraventricular neuroepithelial tumors: surgical outcome, technical considerations and review of literature.

BACKGROUND: Intraventricular neuroepithelial tumors (IVT) are rare lesions and comprise different pathological entities such as ependymomas, subependymomas and central neurocytomas. The treatment of choice is neurosurgical resection, which can be challenging due to their intraventricular location. Different surgical approaches to the ventricles are described. Here we report a large series of IVTs, its postoperative outcome at a single tertiary center and discuss suitable surgical approaches. METHODS: We performed a retrospective chart review at a single tertiary neurosurgical center between 03/2009-05/2019. We included patients that underwent resection of an IVT emphasizing on surgical approach, extent of resection, clinical outcome and postoperative complications. RESULTS: Forty five IVTs were resected from 03/2009 to 05/2019, 13 ependymomas, 21 subependymomas, 10 central neurocytomas and one glioependymal cyst. Median age was 52,5 years with 55.6% (25) male and 44.4% (20) female patients. Gross total resection was achieved in 93.3% (42/45). 84.6% (11/13) of ependymomas, 100% (12/21) of subependymomas, 90% (9/10) of central neurocytomas and one glioependymal cyst were completely removed. Postoperative rate of new neurological deficits was 26.6% (12/45). Postoperative new permanent cranial nerve deficits occurred in one case with 4th ventricle subependymoma and one in 4th ventricle ependymoma. Postoperative KPSS was 90% (IR 80-100). 31.1% of the patients improved in KPSS, 48.9% remained unchanged and 20% declined. Postoperative adverse events rate was 20.0%. Surgery-related mortality was 2.2%. The rate of shunt/cisternostomy-dependent hydrocephalus was 13.3% (6/45). 15.4% of resected ependymomas underwent adjuvant radiotherapy. Mean follow-up was 26,9 (±30.1) months. CONCLUSION: Our surgical findings emphasize satisfactory complete resection throughout all entities. Surgical treatment can remain feasible, if institutional experience is given. Satisfying long-term survival and cure is possible by complete removal. Gross total resection should always be performed under function-remaining aspects due to mostly benign or slow growing nature of IVTs. Further data is needed to evaluate standard of care and alternative therapy options in rare cases of tumor recurrence or in case of patient collective not suitable for operative resection.

In vivo screening of multiple bacterial strains identifies Lactobacillus rhamnosus Lb102 and Bifidobacterium animalis ssp. lactis Bf141 as probiotics that improve metabolic disorders in a mouse model of obesity.

Given the growing evidence that gut dysfunction, including changes in gut microbiota composition, plays a critical role in the development of inflammation and metabolic diseases, the identification of novel probiotic bacteria with immunometabolic properties has recently attracted more attention. Herein, bacterial strains were first isolated from dairy products and human feces and then screened in vitro for their immunomodulatory activity. Five selected strains were further analyzed in vivo, using a mouse model of diet-induced obesity. C57BL/6 mice were fed a high-fat high-sucrose diet, in combination with 1 of 3 Lactobacillus strains (Lb38, L. plantarum; L79, L. paracasei/casei; Lb102, L. rhamnosus) or Bifidobacterium strains (Bf26, Bf141, 2 different strains of B. animalis ssp. lactis species) administered for 8 wk at 109 colony-forming units/d. Whereas 3 strains showed only modest (Lb38, Bf26) or no (L79) effects, Lb102 and Bf141 reduced diet-induced obesity, visceral fat accretion, and inflammation, concomitant with improvement of glucose tolerance and insulin sensitivity. Further analysis revealed that Lb102 and Bf141 enhanced intestinal integrity markers in association with selective changes in gut microbiota composition. We have thus identified 2 new potential probiotic bacterial strains with immunometabolic properties to alleviate obesity development and associated metabolic disturbances.-Le Barz, M., Daniel, N., Varin, T. V., Naimi, S., Demers-Mathieu, V., Pilon, G., Audy, J., Laurin, E., Roy, D., Urdaci, M. C., St-Gelais, D., Fliss, I, Marette, A. In vivo screening of multiple bacterial strains identifies Lactobacillus rhamnosus Lb102 and Bifidobacterium animalis ssp. lactis Bf141 as probiotics that improve metabolic disorders in a mouse model of obesity.

Perioperative neurocognitive functions in patients with neuroepithelial intracranial tumors.

PURPOSE: This study aimed to assess perioperative neurocognitive functions in patients with surgery for intracranial neuroepithelial tumors. METHODS: Seventy-one patients [38 male, 33 female, mean age 47.2 years (range 18 to 81)] with surgery for an intracranial neuroepithelial tumor were included in this prospective single-center study. Mini-mental status examination (MMSE) and extensive neurocognitive testing (divided into the categories attention, memory, and executive functions and adjusted for age, sex, and education) were performed pre-(t0) and early postoperatively (t1). Part of the patient cohort (n = 32) also underwent neurocognitive testing during follow-up (t2). The Karnofsky Performance Status Scale (KPS) was used to assess patients' functional independence. Patients' quality of life was recorded by the Short Form 36 (SF 36) pre- and postoperatively in a part of the patient cohort. Pre- and postoperative comparisons were performed using the Wilcoxon-test for paired samples. Post hoc Bonferroni correction was performed to adjust for multiple testing. To assess the influence of risk factors on neurocognitive functions, Spearman correlations and the chi-squared test were performed. Subgroup analyses for patients with low-grade and high-grade tumors were performed. RESULTS: Postoperative deterioration was observed in 5 of 39 subtests of extensive neurocognitive testing in all 3 categories, whereas no improvement was shown. Patients with WHO Grade I tumors showed no deterioration of cognitive functions. Patients with WHO Grade II and III tumors showed significantly worse results in the executive functions category patients with WHO Grade IV tumors showed deterioration in the attention category. Significantly worse functional independence was recorded postoperatively and during follow-up (P < 0.001). Patients reported poorer physical health (SF 36, P = 0.001) at t1, whereas mental health did not differ significantly (P = 0.480). Risk factors for postoperative deterioration of cognition are low KPS scores, postoperative radiotherapy and tumor location in the temporal lobe. CONCLUSIONS: After surgery on an intracranial neuroepithelial tumor, early postoperative deterioration of neurocognitive functions, functional independence and physical health occur. Similar results were also shown during follow-up suggesting that these effects are not only due to postoperative systemic factors or fatigue. This knowledge might improve perioperative surveillance of neurocognitive functions.

Treatment with camu camu (Myrciaria dubia) prevents obesity by altering the gut microbiota and increasing energy expenditure in diet-induced obese mice.

OBJECTIVE: The consumption of fruits is strongly associated with better health and higher bacterial diversity in the gut microbiota (GM). Camu camu (Myrciaria dubia) is an Amazonian fruit with a unique phytochemical profile, strong antioxidant potential and purported anti-inflammatory potential. DESIGN: By using metabolic tests coupled with 16S rRNA gene-based taxonomic profiling and faecal microbial transplantation (FMT), we have assessed the effect of a crude extract of camu camu (CC) on obesity and associated immunometabolic disorders in high fat/high sucrose (HFHS)-fed mice. RESULTS: Treatment of HFHS-fed mice with CC prevented weight gain, lowered fat accumulation and blunted metabolic inflammation and endotoxaemia. CC-treated mice displayed improved glucose tolerance and insulin sensitivity and were also fully protected against hepatic steatosis. These effects were linked to increased energy expenditure and upregulation of uncoupling protein 1 mRNA expression in the brown adipose tissue (BAT) of CC-treated mice, which strongly correlated with the mRNA expression of the membrane bile acid (BA) receptor TGR5. Moreover, CC-treated mice showed altered plasma BA pool size and composition and drastic changes in the GM (eg, bloom of Akkermansia muciniphila and a strong reduction of Lactobacillus). Germ-free (GF) mice reconstituted with the GM of CC-treated mice gained less weight and displayed higher energy expenditure than GF-mice colonised with the FM of HFHS controls. CONCLUSION: Our results show that CC prevents visceral and liver fat deposition through BAT activation and increased energy expenditure, a mechanism that is dependent on the GM and linked to major changes in the BA pool size and composition.

Role of postoperative tumor volume in patients with MGMT-unmethylated glioblastoma.

PURPOSE: The aim of this study is to investigate the association between postoperative tumor volume and overall survival (OS) of O6-methylguanine DNA methyltransferase (MGMT)-unmethylated glioblastoma patients. METHODS: One hundred-twenty-six patients with MGMT-unmethylated glioblastoma who were treated either with surgical resection or needle biopsy between 2006 and 2015 were included in this retrospective cohort. Pre- and postcontrast T1 weighted images were evaluated in order to determine pre- and postoperative contrast-enhancing tumor volumes (CE-TV). Cox regression models adjusted for other significant prognostic factors were used to investigate the association between postoperative tumor volume and survival. RESULTS: Complete resection of CE-TV was significantly associated with longer OS in the univariate analysis (HR 0.61; 95% CI 0.40-0.94; p = 0.02). However, this fact could not be confirmed after adjusting the model for other relevant prognostic factors (HR 1.01; 95% CI 0.65-1.55; p = 0.962). Postoperative CE-TV was significantly associated with survival in both univariate (HR: 1.04; 95% CI 1.025-1.055; p < 0.001) and multivariate analyses (HR: 1.027; 95% CI 1.005-1.049; p = 0.014). CONCLUSIONS: Although complete resection of tumor tissue was not significantly associated with longer OS in MGMT-unmethylated GBM patients, maximum safe resection should always be attempted, since postoperative tumor volume is strongly associated with OS.

ALDH1 - A new immunohistochemical diagnostic marker for Schwann cell-derived tumors.

Although Schwann cell-derived tumors show typical histological features, the broad variety of spindle cell tumors that exist can impede the diagnostic procedure. In this study, we present aldehyde dehydrogenase 1 (ALDH1) as a new, viable diagnostic marker for Schwann cell tumors. Protein expression was examined by immunohistochemistry in schwannomas, neurofibromas, and malignant peripheral nerve sheath tumors (MPNST) as well as in non-neoplastic peripheral nerve sheath specimens. Meningiomas and other spindle cell-like tumors served as control tissue. ALDH1 immunohistochemistry was performed on human FFPE samples. Staining evaluation was performed according to a defined immunoreactive score. All schwannomas and neurofibromas were strongly positive for ALDH1. MPNST were positive too, but with a clear reduction of ALDH1 expression. All non-Schwann-cell-derived tumors showed no immunoreaction. This leads to the conclusion that ALDH1 can serve a as viable diagnostic marker for schwannomas and neurofibromas as it was expressed and detected by IHC in all samples. Furthermore, ALDH1 expression seems to be a sign for differentiation as it diminishes during malignization of Schwann cell tumors. Hence, its expression level provides information about the biological behavior of the tumor.

Arctic berry extracts target the gut-liver axis to alleviate metabolic endotoxaemia, insulin resistance and hepatic steatosis in diet-induced obese mice.

AIMS/HYPOTHESIS: There is growing evidence that fruit polyphenols exert beneficial effects on the metabolic syndrome, but the underlying mechanisms remain poorly understood. In the present study, we aimed to analyse the effects of polyphenolic extracts from five types of Arctic berries in a model of diet-induced obesity. METHODS: Male C57BL/6 J mice were fed a high-fat/high-sucrose (HFHS) diet and orally treated with extracts of bog blueberry (BBE), cloudberry (CLE), crowberry (CRE), alpine bearberry (ABE), lingonberry (LGE) or vehicle (HFHS) for 8 weeks. An additional group of standard-chow-fed, vehicle-treated mice was included as a reference control for diet-induced obesity. OGTTs and insulin tolerance tests were conducted, and both plasma insulin and C-peptide were assessed throughout the OGTT. Quantitative PCR, western blot analysis and ELISAs were used to assess enterohepatic immunometabolic features. Faecal DNA was extracted and 16S rRNA gene-based analysis was used to profile the gut microbiota. RESULTS: Treatment with CLE, ABE and LGE, but not with BBE or CRE, prevented both fasting hyperinsulinaemia (mean ± SEM [pmol/l]: chow 67.2 ± 12.3, HFHS 153.9 ± 19.3, BBE 114.4 ± 14.3, CLE 82.5 ± 13.0, CRE 152.3 ± 24.4, ABE 90.6 ± 18.0, LGE 95.4 ± 10.5) and postprandial hyperinsulinaemia (mean ± SEM AUC [pmol/l × min]: chow 14.3 ± 1.4, HFHS 31.4 ± 3.1, BBE 27.2 ± 4.0, CLE 17.7 ± 2.2, CRE 32.6 ± 6.3, ABE 22.7 ± 18.0, LGE 23.9 ± 2.5). None of the berry extracts affected C-peptide levels or body weight gain. Levels of hepatic serine phosphorylated Akt were 1.6-, 1.5- and 1.2-fold higher with CLE, ABE and LGE treatment, respectively, and hepatic carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-1 tyrosine phosphorylation was 0.6-, 0.7- and 0.9-fold increased in these mice vs vehicle-treated, HFHS-fed mice. These changes were associated with reduced liver triacylglycerol deposition, lower circulating endotoxins, alleviated hepatic and intestinal inflammation, and major gut microbial alterations (e.g. bloom of Akkermansia muciniphila, Turicibacter and Oscillibacter) in CLE-, ABE- and LGE-treated mice. CONCLUSIONS/INTERPRETATION: Our findings reveal novel mechanisms by which polyphenolic extracts from ABE, LGE and especially CLE target the gut-liver axis to protect diet-induced obese mice against metabolic endotoxaemia, insulin resistance and hepatic steatosis, which importantly improves hepatic insulin clearance. These results support the potential benefits of these Arctic berries and their integration into health programmes to help attenuate obesity-related chronic inflammation and metabolic disorders. DATA AVAILABILITY: All raw sequences have been deposited in the public European Nucleotide Archive server under accession number PRJEB19783 ( https://www.ebi.ac.uk/ena/data/view/PRJEB19783 ).

Correction to: Prognostic Value of Tumor Volume in Glioblastoma Patients: Size Also Matters for Patients with Incomplete Resection.

Due to a metadata tagging error the names of Stephanie E. Combs and Jan S. Kirschke were indexed incorrectly. Stephanie E. is the author's given name, and Jan S. is the author's given name.

Prognostic Value of Tumor Volume in Glioblastoma Patients: Size Also Matters for Patients with Incomplete Resection.

BACKGROUND: Incomplete resection of glioblastoma is discussed controversially in the era of combined radiochemotherapy. OBJECTIVE: The aim of this study was to analyze the benefit of subtotal tumor resection for glioblastoma patients as this was recently questioned in the era of radiochemotherapy. METHODS: Overall, 209 patients undergoing surgery for newly diagnosed WHO grade IV gliomas were retrospectively analyzed, and pre- and postoperative tumor volumes were manually segmented (cm3). Survival analyses were performed, including prognostic factors such as age, Karnofsky performance score (KPS), O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status, and adjuvant treatment regimen. RESULTS: Pre- and postoperative tumor volume is significantly associated with pre- and postoperative KPS, as well as age (p < 0.001). Postoperative tumor volume remained a significant prognostic factor in a multivariate analysis, independent of other prognostic factors (hazard ratio 1.0365, 95% confidence interval 1.0235-1.0497, p < 0.001). CONCLUSIONS: In the era of molecularly-driven radiochemotherapy, glioblastoma surgery remains a major prognostic factor. Even in situations in which a gross total resection cannot be achieved, maximum safe reduction of tumor burden should be attempted.

Impact of ischemic preconditioning on surgical treatment of brain tumors: a single-center, randomized, double-blind, controlled trial.

BACKGROUND: Postoperative ischemia is a frequent phenomenon in patients with brain tumors and is associated with postoperative neurological deficits and impaired overall survival. Particularly in the field of cardiac and vascular surgery, the application of a brief ischemic stimulus not only in the target organ but also in remote tissues can prevent subsequent ischemic damage. We hypothesized that remote ischemic preconditioning (rIPC) in patients with brain tumors undergoing elective surgical resection reduces the incidence of postoperative ischemic tissue damage and its consequences. METHODS: Sixty patients were randomly assigned to two groups, with 1:1 allocation, stratified by tumor type (glioma or metastasis) and previous treatment with radiotherapy. rIPC was induced by inflating a blood pressure cuff placed on the upper arm three times for 5 min at 200 mmHg in the treatment group after induction of anesthesia. Between the cycles, the blood pressure cuff was released to allow reperfusion. In the control group no preconditioning was performed. Early postoperative magnetic resonance images (within 72 h after surgery) were evaluated by a neuroradiologist blinded to randomization for the presence of ischemia and its volume. RESULTS: Fifty-eight of the 60 patients were assessed for occurrence of postoperative ischemia. Of these 58 patients, 44 had new postoperative ischemic lesions. The incidence of new postoperative ischemic lesions was significantly higher in the control group (27/31) than in the rIPC group (17/27) (p = 0.03). The median infarct volume was 0.36 cm3 (interquartile range (IR): 0.0-2.35) in the rIPC group compared with 1.30 cm3 (IR: 0.29-3.66) in the control group (p = 0.09). CONCLUSIONS: Application of rIPC was associated with reduced incidence of postoperative ischemic tissue damage in patients undergoing elective brain tumor surgery. This is the first study indicating a benefit of rIPC in brain tumor surgery. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00010409 . Retrospectively registered on 13 October 2016.

Psychobiotics and the Microbiota-Gut-Brain Axis: Where Do We Go from Here?

The bidirectional relationship between the gut microbiota and the nervous system is known as the microbiota-gut-brain axis (MGBA). The MGBA controls the complex interactions between the brain, the enteric nervous system, the gut-associated immune system, and the enteric neuroendocrine systems, regulating key physiological functions such as the immune response, sleep, emotions and mood, food intake, and intestinal functions. Psychobiotics are considered tools with the potential to modulate the MGBA through preventive, adjunctive, or curative approaches, but their specific mechanisms of action on many aspects of health are yet to be characterized. This narrative review and perspectives article highlights the key paradigms needing attention as the scope of potential probiotics applications in human health increases, with a growing body of evidence supporting their systemic beneficial effects. However, there are many limitations to overcome before establishing the extent to which we can incorporate probiotics in the management of neuropsychiatric disorders. Although this article uses the term probiotics in a general manner, it remains important to study probiotics at the strain level in most cases.

Inhibition of intestinal FXR activity as a possible mechanism for the beneficial effects of a probiotic mix supplementation on lipid metabolism alterations and weight gain in mice fed a high fat diet.

Supplementation with probiotics has emerged as a promising therapeutic tool to manage metabolic diseases. We investigated the effects of a mix of Bifidobacterium animalis subsp. lactis LA804 and Lactobacillus gasseri LA806 on high-fat (HF) diet -induced metabolic disease in mice. Supplementation with the probiotic mix in HF diet-fed mice (HF-Pr2) reduced weight and fat mass gains, decreased hepatic lipid accumulation, and lowered plasma triglyceride peak during an oral lipid tolerance test. At the molecular level, the probiotic mix protected against HF-induced rise in mRNA levels of genes related to lipid uptake, metabolism, and storage in the liver and white adipose tissues, and strongly decreased mRNA levels of genes related to inflammation in the white adipose tissue and to oxidative stress in the liver. Regarding intestinal homeostasis, the probiotic mix did not prevent HF-induced gut permeability but slightly modified microbiota composition without correcting the dysbiosis induced by the HF diet. Probiotic supplementation also modified the cecal bile acid (BA) profile, leading to an increase in the Farnesoid-X-Receptor (FXR) antagonist/agonist ratio between BA species. In agreement, HF-Pr2 mice exhibited a strong inhibition of FXR signaling pathway in the ileum, which was associated with lipid metabolism protection. This is consistent with recent reports proposing that inhibition of intestinal FXR activity could be a potent mechanism to overcome metabolic disorders. Altogether, our results demonstrate that the probiotic mix evaluated, when administered preventively to HF diet-fed mice could limit obesity and associated lipid metabolism disorders, likely through the inhibition of FXR signaling in the intestinal tract.