Correlation between Mild Traumatic Brain Injury-Induced Inflammatory Cytokines and Emotional Symptom Traits: A Systematic Review

Both mild traumatic brain injuries (mTBI) and systemic injuries trigger a transient neuroinflammatory response that result in similar clinical outcome. The ensuing physical, cognitive, and emotional symptoms fail to subside in approximately 15–20% of the concussed population. Emotional impairments, particularly depression, anxiety, and post-traumatic stress disorder (PTSD), are commonly associated with poor recovery following mTBI. These emotional impairments also have a significant neuroinflammatory component. We hypothesized that the inflammatory cytokines seen in mTBI patients with emotional symptoms would coincide with those commonly seen in patients with emotional symptoms without mTBI. A systematic review was conducted to identify the most common neuroinflammatory cytokines in the mTBI population with psychological symptoms (depression, anxiety, PTSD). The electronic databases EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED, and PSYCINFO were searched from data inception to 31 August 2021. A systematic screening approach was employed from screening to data analysis. A total of 994 articles were screened, 108 were selected for full article review, and 8 were selected for data analysis. The included studies consisted of 875 patients of which 81.3% were male. The mean sample size of patients with at least one mTBI was 73.8 ± 70.3 (range, 9–213), with a mean age of 33.9 ± 4.8 years. The most common cytokines associated with poor psychological outcomes involving PTSD and/or depression in the chronic mTBI population were IL-6, TNFα, IL-10, and CRP.

Endovascular revascularization strategies using catheter-based thrombectomy versus conventional catheter-directed thrombolysis for acute limb ischemia

Background Acute limb ischemia (ALI) is an important clinical event threatening both life and the affected limbs, but the optimal treatment for ALI remains undefined. The aim of this study was to compare the safety and effectiveness of thrombectomy approaches via either catheter-based thrombectomy (CBT) or catheter-directed thrombolysis (CDT). Methods A total of 98 patients (mean age 69.7 years, 60 male) who underwent endovascular intervention for ALI from January 2015 to July 2019 were included. Of these, 57 were treated with primary CBT via a large-bore catheter, an AngioJet catheter or Rotarex catheter, and/or underwent low-dose CDT, and 41 were treated with primary CDT. The safety and effectiveness of CBT compared to conventional CDT and other various endovascular techniques were evaluated. Results More Rutherford IIb patients were treated with primary CBT (68.4%) than CDT (26.8%; P < .001). Patients who underwent primary CDT achieved a higher technical success rate than those who underwent primary CBT in a shorter procedure time (P < .001), whereas 42.1% of patients who underwent CBT did not need adjunctive CDT. The duration and dosage of adjunctive CDT in the CBT group were significantly decreased compared with those in the primary CDT group (both P < .001), and the CBT group achieved a shorter in-hospital length of stay (P < .001). Subgroup analysis revealed that patients treated with AngioJet and Rotarex catheters achieved slightly lower dosages, shorter CDT durations and shorter in-hospital stay lengths than those treated with large-bore catheters (P > .05). Clinical success was estimated to be achieved in 98.2% of patients who underwent CBT, which is similar to the 97.6% estimated in those who underwent primary CDT (P = 1.000), and this finding was similar among the CBT subgroups. Patients who underwent CBT had a higher procedure-related distal embolization rate and economic cost than those who underwent primary CDT (P < .05), but it had slightly fewer complications than those who underwent primary CDT (P = .059), especially minor complications (P = .036). The freedom from amputation at 6 and 12 months for CBT and CDT was assessed (93.0% vs 90.2% respectively, P = .625; 89.5% vs 82.9%, respectively, P = .34,). Comparable limb salvage was found for different techniques of large bore catheters, AngioJet catheters and Rotarex catheters. The Kaplan-Meier table analysis also showed similar limb salvage rates between groups. Conclusions Endovascular treatment of ALI with the use of catheter-based therapies is an effective modality that can reduce the requirement for thrombolysis, with expected reductions in hemorrhagic complications, but at the risk of remediable distal emboli and increased economic cost. It has a similar clinical outcome to conventional CDT alone. Different CBT techniques have comparable efficacy but different adverse event profiles.

Tenofovir versus lamivudine followed by tenofovir in severe exacerbation of hepatitis B: a randomized controlled study

Spontaneous severe acute exacerbation (SAE) is not uncommon in the natural history of chronic hepatitis B (CHB). Lamivudine (LAM) had the advantages of low price, quick onset, good efficacy and no drug resistance within 24 weeks. This study aimed to compare the short-term efficacy of tenofovir disoproxil fumarate (TDF) and LAM for 24 weeks followed by TDF in the treatment of CHB with severe acute exacerbation. Consecutive patients of CHB with SAE were randomized to receive either TDF (19 patients) or LAM for 24 weeks followed by TDF (18 patients). The primary endpoint was overall mortality or receipt of liver transplantation by week 24. This study was approved by the Institutional Review Board (IRB) of the Kaohsiung Veterans General Hospital (VGHKS12-CT5-10). The baseline characteristics were comparable between the two groups. By week 24, seven (37%) and five (28%) patients in the TDF and LAM/TDF groups died or received liver transplantation (P=0.487). Multivariate analysis showed that albumin level, prothrombin time (PT), and hepatic encephalopathy were independent factors associated with mortality or liver transplantation by week 24. Early reductions in HBV DNA of more than or equal to 2 log at 1 and 2 weeks were similar between the two groups. The biochemical and virological responses at 12, 24 and 48 weeks were also similar between the two groups. TDF and LAM for 24 weeks followed by TDF achieved a similar clinical outcome in CHB patients with SAE.

Propensity score-adjusted analysis on stent-assisted coiling versus coiling alone for ruptured intracranial aneurysms

Stent-assisted coiling (SAC) for ruptured intracranial aneurysms (RIAs) remains controversial due to an inherent risk of potential thromboembolic and hemorrhagic complications. We compared SAC and coiling alone for the management of RIAs using propensity score-adjustment. Sixty-four patients treated by SAC and 220 by stand-alone coiling were retrospectively reviewed and compared using inverse probability of treatment weighting (IPTW) with propensity scores. Functional outcome, procedure-related and overall complications and angiographic results were analyzed. Aneurysms treated by SAC had a larger diameter, a wider neck and were more frequently located at the posterior circulation. SAC had a higher risk for thromboembolic complications (17.2% vs. 7.7%, p = 0.025), however, this difference did not persist in the IPTW analysis (OR 1.2, 95% CI 0.7–2.3, adjusted p = 0.458). In the adjusted analysis, rates of procedural cerebral infarction (p = 0.188), ventriculostomy-related hemorrhage (p = 0.584), in-hospital mortality (p = 0.786) and 6-month favorable functional outcome (p = 0.471) were not significantly different between the two groups. SAC yielded a higher complete occlusion (80.0% vs. 67.2%, OR 3.2, 95% CI 1.9–5.4, p < 0.001) and a lower recanalization rate (17.5% vs. 26.1%, OR 0.3, 95% CI 0.2–0.6, p < 0.001) than stand-alone coiling at 6-month follow-up. In conclusion, SAC of large and wide-necked RIAs provided higher aneurysm occlusion and similar clinical outcome, when compared to stand-alone coiling.

P–515 Clinical outcome of mosaic-blastocyst transfer versus euploid-blastocyst transfer in single frozen blastocyst transfer cycles

Study question What is the clinical outcome of transferring a mosaic blastocyst versus a euploid blastocyst in single frozen blastocyst transfer (sFBT) cycles? Summary answer Single mosaic blastocyst transfer has similar clinical outcome to single euploid blastocyst transfer. What is known already Embryonic mosaicism occurs when there are two or more distinct cell lines found in preimplantation embryos derived from IVF. Data from recent studies show that mosaic blastocysts have the potential to implant and can result in healthy live births. As a result, patients now have the option of transferring mosaic blastocyst when they do not have any euploid blastocyst available for transfer. However, the clinical outcome of transferring mosaic blastocyst has not been definitively reported. Thus, a retrospective study was conducted to compare the clinical outcome of mosaic sFBT and euploid sFBT. Study design, size, duration A total of 602 patients underwent frozen blastocyst transfer in Alpha IVF from January to October 2019 and had their blastocysts screened for aneuploidy. These patients were divided into 2 groups: 26 patients with mosaic blastocysts transferred (Group A, age ranged 19–44), and 576 patients with euploid blastocysts transferred (Group B, age ranged 21–44). The mean age of patients from Group A and B were 34.0 and 32.8 respectively (p &gt; 0.05). Participants/materials, setting, methods All samples had their DNA libraries constructed for sequencing using Next Generation Sequencing according to manufacturer’s specification (IonTorrent, USA). All blastocysts were frozen for subsequent sFBT cycle (Cryotech, Japan). All thawed blastocysts for sFBT survived with morphologically intact inner cell mass and trophectoderm cells. The importance of antenatal confirmation of the fetal chromosome status was emphasized in patients from Group A. The clinical outcomes of both groups were analysed and compared. Main results and the role of chance No significant differences were seen in the clinical pregnancy and implantation rate of Group A and B (65.4% vs 63.0%; p &gt; 0.05). The miscarriage rate of Group A and B were 23.5% and 14.0% respectively. Albeit the higher miscarriage rate in Group A, there was no statistical significance between these two groups (p &gt; 0.05). Group A was further divided into two subgroups, Subgroup A1: low risk mosaic blastocyst transfer; Subgroup A2: high risk mosaic blastocyst transfer. In the comparison of Group A subgroups, the clinical pregnancy and implantation of Group A1 is higher than Group A2 (76.9% vs 44.4%). In addition, the miscarriage rate of Group A1 and A2 were 23.1% and 0.0% respectively. Interestingly, there was no statistical significance in clinical pregnancy rate, implantation rate and miscarriage rate between these two subgroups. Limitations, reasons for caution This is a retrospective study and the sample size was comparatively smaller in the mosaic blastocyst transfer group than the euploid blastocyst transfer group. Further studies with a larger sample size should be carried out to ascertain the clinical outcome. Wider implications of the findings: Single mosaic blastocyst transfer has similar clinical outcome to single euploid blastocyst transfer. Thus, mosaic blastocyst can be considered for transfer when no euploid blastocyst are available. Nevertheless, stringent antenatal surveillance for chromosomal abnormalities to confirm the chromosomal status of the fetus must be followed. Trial registration number Not applicable

Cost effectiveness of outpatient lumbar discectomy

Background Microdiscectomy is the most commonly performed spine surgery and the first transitioning for outpatient settings. However, this transition was never studied, in what comes to cost-utility assessment. Accordingly, this economic study aims to access the cost-effectiveness of outpatient lumbar microdiscectomy when compared with the inpatient procedure. Methods This is a cost utility study, adopting the hospital perspective. Direct medical costs were retrieved from the assessment of 20 patients undergoing outpatient lumbar microdiscectomy and 20 undergoing inpatient lumbar microdiscectomy Quality-adjusted life-years were calculated from Oswestry Disability Index values (ODI). ODI was prospectively assessed in outpatients in pre and 3- and 6-month post-operative evaluations. Inpatient ODI data were estimated from a meta-analysis. A probabilistic sensitivity analysis was performed and incremental cost-effectiveness ratio (ICER) calculated. Results Outpatient procedure was cost-saving in all models tested. At 3-month assessment ICER ranged from €135,753 to €345,755/QALY, higher than the predefined threshold of €60,000/QALY gained. At 6-month costs were lower and utilities were higher in outpatient, overpowering the inpatient procedure. Probabilistic sensitivity analysis showed that in 65% to 73% of simulations outpatient was the better option. The savings with outpatient were about 55% of inpatient values, with similar utility scores. No 30-day readmissions were recorded in either group. Conclusion This is the first economic study on cost-effectiveness of outpatient lumbar microdiscectomy, showing a significant reduction in costs, with a similar clinical outcome, proving it cost-effective.

Molecular Correlates of Long Survival in IDH-Wildtype Glioblastoma Cohorts

IDH-wildtype glioblastoma is a relatively common malignant brain tumor in adults. These patients generally have dismal prognoses, although outliers with long survival have been noted in the literature. Recently, it has been reported that many histologically lower-grade IDH-wildtype astrocytomas have a similar clinical outcome to grade IV tumors, suggesting they may represent early or undersampled glioblastomas. cIMPACT-NOW 3 guidelines now recommend upgrading IDH-wildtype astrocytomas with certain molecular criteria (EGFR amplifications, chromosome 7 gain/10 loss, and/or TERT promoter mutations), establishing the concept of a “molecular grade IV” astrocytoma. In this report, we apply these cIMPACT-NOW 3 criteria to 2 independent glioblastoma cohorts, totaling 393 public database and institutional glioblastoma cases: 89 cases without any of the cIMPACT-NOW 3 criteria (GBM-C0) and 304 cases with one or more criteria (GBM-C1-3). In the GBM-C0 groups, there was a trend toward longer recurrence-free survival (median 12–17 vs 6–10 months), significantly longer overall survival (median 32–41 vs 15–18 months), younger age at initial diagnosis, and lower overall mutation burden compared to the GBM-C1-3 cohorts. These data suggest that while histologic features may not be ideal indicators of patient survival in IDH-wildtype astrocytomas, these 3 molecular features may also be important prognostic factors in IDH-wildtype glioblastoma.