The glymphatic system for neurosurgeons: a scoping review.

The discovery of the glymphatic system has revolutionized our understanding of cerebrospinal fluid (CSF) circulation and interstitial waste clearance in the brain. This scoping review aims to synthesize the current literature on the glymphatic system's role in neurosurgical conditions and its potential as a therapeutic target. We conducted a comprehensive search in PubMed and Scopus databases for studies published between January 1, 2012, and October 31, 2023. Studies were selected based on their relevance to neurosurgical conditions and glymphatic function, with both animal and human studies included. Data extraction focused on the methods for quantifying glymphatic function and the main results. A total of 67 articles were included, covering conditions such as idiopathic normal pressure hydrocephalus (iNPH), idiopathic intracranial hypertension (IIH), subarachnoid hemorrhage (SAH), stroke, intracranial tumors, and traumatic brain injury (TBI). Significant glymphatic dysregulation was noted in iNPH and IIH, with evidence of impaired CSF dynamics and delayed clearance. SAH studies indicated glymphatic dysfunction with the potential therapeutic effects of nimodipine and tissue plasminogen activator. In stroke, alterations in glymphatic activity correlated with the extent of edema and neurological recovery. TBI studies highlighted the role of the glymphatic system in post-injury cognitive outcomes. Results indicate that the regulation of aquaporin-4 (AQP4) channels is a critical target for therapeutic intervention. The glymphatic system plays a critical role in the pathophysiology of various neurosurgical conditions, influencing brain edema and CSF dynamics. Targeting the regulation of AQP4 channels presents as a significant therapeutic strategy. Although promising, the translation of these findings into clinical practice requires further human studies. Future research should focus on establishing non-invasive biomarkers for glymphatic function and exploring the long-term effects of glymphatic dysfunction.

Incidence, management, and outcome of incidental meningioma: what has happened in 10 years?

PURPOSE: The aim of this study was to study the use of brain scanning, and the subsequent findings of presumed incidental meningioma in two time periods, and to study differences in follow-up, treatment, and outcome. METHODS: Records of all performed CT and MRI of the brain during two time periods were retrospectively reviewed in search of patients with presumed incidental meningioma. These patients were further analyzed using medical health records, with the purpose to study clinical handling and outcome during a 3 year follow up. RESULTS: An identical number of unique patients underwent brain imaging during the two time periods (n = 22 259 vs. 22 013). In 2018-2019, 25% more incidental meningiomas were diagnosed compared to 2008-2009 (n = 161 vs. 129, p = 0.052). MRI was used more often in 2018-2019 (26.1 vs. 12.4%, p = 0.004), and the use of contrast enhancement, irrespective of modality, also increased (26.8 vs. 12.2%, p < 0.001). In the most recent cohort, patients were older (median 79 years vs. 73 years, p = 0.03). Indications showed a significant increase of cancer without known metastases among scanned patients. 29.5 and 35.4% of patients in the cohorts were deceased 3 years after diagnosis for causes unrelated to their meningioma. CONCLUSIONS: Despite the same number of unique patients undergoing brain scans in the time periods, there was a trend towards more patients diagnosed with an incidental asymptomatic meningioma in the more recent years. This difference may be attributed to more contrast enhanced scans and more scans among the elderly but needs to be further studied. Patients in the cohort from 2018 to 2019 more often had non-metastatic cancer, with their cause of scan screening for metastases. There was no significant difference in management decision at diagnosis, but within 3 years of follow up significantly more patients in the latter cohort had been re-scanned. Almost a third of all patients were deceased within 3 years after diagnosis, due to causes other than their meningioma.

Low-grade intestinal inflammation two decades after pelvic radiotherapy.

BACKGROUND: Radiotherapy is effective in the treatment of cancer but also causes damage to non-cancerous tissue. Pelvic radiotherapy may produce chronic and debilitating bowel symptoms, yet the underlying pathophysiology is still undefined. Most notably, although pelvic radiotherapy causes an acute intestinal inflammation there is no consensus on whether the late-phase pathophysiology contains an inflammatory component or not. To address this knowledge gap, we examined the potential presence of a chronic inflammation in mucosal biopsies from irradiated pelvic cancer survivors. METHODS: We biopsied 24 cancer survivors two to 20 years after pelvic radiotherapy, and four non-irradiated controls. Using tandem mass tag (TMT) mass spectrometry and mRNA sequencing (mRNA-seq), we charted proteomic and transcriptomic profiles of the mucosal tissue previously exposed to a high or a low/no dose of radiation. Changes in the immune cell populations were determined with flow cytometry. The integrity of the protective mucus layers were determined by permeability analysis and 16S rRNA bacterial detection. FINDINGS: 942 proteins were differentially expressed in mucosa previously exposed to a high radiation dose compared to a low radiation dose. The data suggested a chronic low-grade inflammation with neutrophil activity, which was confirmed by mRNA-seq and flow cytometry and further supported by findings of a weakened mucus barrier with bacterial infiltration. INTERPRETATION: Our results challenge the idea that pelvic radiotherapy causes an acute intestinal inflammation that either heals or turns fibrotic without progression to chronic inflammation. This provides a rationale for exploring novel strategies to mitigate chronic bowel symptoms in pelvic cancer survivors. FUNDING: This study was supported by the King Gustav V Jubilee Clinic Cancer Foundation (CB), The Adlerbertska Research Foundation (CB), The Swedish Cancer Society (GS), The Swedish State under the ALF agreement (GS and CB), Mary von Sydow's foundation (MA and VP).

The effect of androstenedione supplementation on testosterone, estradiol, body composition, and lipid profile: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To date, no meta-analysis has been carried out to collect evidence from randomized placebo-controlled trials (RCTs) for the purpose of comprehensively summarizing the effect of androstenedione supplementation. Therefore, the aim of this research was to perform a systematic review and meta-analysis of all RCTs that explored the effect of androstenedione supplementation on individual hormonal, lipid, and anthropometric indices. METHODS: We searched five databases (Web of Science, SCOPUS, Embase, PubMed/MEDLINE, and Google Scholar) using a combination of medical subject headings (MeSH) and non-MeSH terms. Using the random-effects model, we summarized the outcomes as weighted mean difference (WMD) with 95% confidence interval (CI). RESULTS: Eight eligible articles were included in the meta-analysis. The pooled effect sizes suggested a significant effect of androstenedione supplementation on serum estradiol concentrations (WMD: 20.82 ng/ml, 95% CI: 7.25 to 34.38, p = 0.003), triglycerides (TG, WMD: -0.19 mg/dl, 95% CI: - 0.96, 0.57, p = 0.000), and high-density lipoprotein (HDL)-cholesterol (WMD: - 0.13 mg/dl, 95% CI: - 0.23 to - 0.03, p = 0.009); however, it had no effect on testosterone (WMD: 0.098 ng/ml, 95% CI: - 0.499 to 0.696, p = 0.748), body weight (WMD: 0.579 kg, 95% CI: - 4.02 to 5.17, p = 0.805), body mass index (BMI, WMD: - 0.73 kg/m2, 95% CI: - 2.98, 1.50, p = 0.519), low-density lipoprotein (LDL)-cholesterol (WMD: - 0.074 mg/dl, 95% CI: - 0.37 to 0.22, p = 0.622), and total cholesterol (TC, WMD: - 0.15 mg/dl, 95% CI: - 0.49, 0.17, p = 0.198). CONCLUSION: These findings indicate that androstenedione supplementation can lower TG and HDL-cholesterol and increase estradiol concentrations.

The effect of transdermal 17ß-estradiol combined with norethisterone acetate treatment on the lipid profile in postmenopausal women: A meta-analysis and systematic review of randomized controlled trials.

BACKGROUND AND AIM: The effect of transdermal 17ß-estradiol and norethisterone acetate co-administration on the lipid profile in postmenopausal women remains controversial as randomized controlled trials (RCTs) conducted to investigate this research question have produced conflicting results. Consequently, to clarify this issue, we conducted a systematic review and meta-analysis of RCTs that evaluated the impact of transdermal 17ß-estradiol combined with norethisterone acetate treatment on the concentrations of serum lipids in postmenopausal women. METHODS: Relevant articles published before February 1st, 2022 were identified by searching the PubMed/Medline, Scopus, and Embase, and Web of Science electronic databases. A random-effects model, employing the method of DerSimonian and Laird, was used to evaluate effect sizes, and results were expressed as weighted mean difference (WMD) and 95% confidence intervals (CIs). RESULTS: Pooled results from 7 RCTs with 9 intervention arms demonstrated that transdermal 17ß-estradiol combined with norethisterone acetate administration significantly decreased total cholesterol (TC) (WMD: -13.43 mg/dL, 95% CI: -18.11 to -8.75, P < 0.001) and low-density lipoprotein cholesterol (LDL-C) (WMD: -13.90 mg/dL, 95% CI: -20.40 to -7.41, P < 0.001). In the subgroup analyses, a notable reduction in TC was observed in subjects with baseline TC concentrations ≥ 130 mg/dL (WMD -14.49 mg/dL), when treatment duration was ≤ 6 months (WMD: -17.21 mg/dL), and in participants with a body mass index (BMI) ≥ 25 kg/m2 (WMD: -21.71 mg/dL). Moreover, in the subgroup analyses, transdermal 17ß-estradiol combined with norethisterone acetate decreased triglycerides (TG) levels when the treatment duration was ≤ 6 months (WMD: -21.37 mg/dL). However, the prescription of transdermal 17ß-estradiol combined with norethisterone acetate in postmenopausal women did not change high-density lipoprotein cholesterol (HDL-C) values. CONCLUSIONS: Based on our findings, the co-administration of transdermal 17ß-estradiol and norethisterone acetate in postmenopausal females can decrease TC and LDL-C levels, as well as TG values, but does not influence HDL-C concentrations.

BRAF V600E mutation in papillary thyroid carcinoma: it's relation to clinical features and oncologic outcomes in a single cancer centre experience.

PURPOSE: This study focuses on the oncologic influence of BRAF V600E mutations in a cohort of Middle Eastern papillary thyroid carcinoma (PTC) patients treated at a single centre. We tested the association of BRAF V600E mutation with papillary thyroid carcinoma at King Hussein Cancer Center. METHODS: Patients with histologically confirmed PTC who underwent surgical treatment between 2006 and 2015 were included in this study. Oncological outcomes, both short- and long-termed, were collected. RESULTS: A total of 128 patients (68% females) were included in this study with a mean age of 38 years (±13.8). The median follow-up period was 50 months. The BRAF V600E mutation was found in 71% of patients. The tumour size for patients with a negative BRAF V600E mutation was significantly larger in comparison to patients who tested positive for the mutation (3.47 cm vs 2.31 cm, respectively, P = 0.009). The two groups showed similar disease-free survival (DFS) rates; positive = 75% (median 43 months (0-168)) compared to 78% for the negative BRAF V600E mutation (median 38 months (3-142)) (P = 0.162, HR = 0.731) Furthermore, both groups showed similar overall survival rates, positive = 94.5% (median 56 months (0-228)) compared to 94.6% for the negative BRAF V600E mutation (median 43 months (3-157)) (P = 0.941, HR = 0.940). CONCLUSION: BRAF V600E mutation had no effect on loco-regional recurrence, distant metastasis, overall survival, or DFS. These findings may be attributed to geographic variations or reflect that BRAF V600E may only serve as an indicator of poor prognosis in high-risk group as such.