Conventional management of patients with neurotrauma frequently consists of routine, repeat head CT at preordained intervals with ICU-level monitoring, regardless of injury severity. The Brain Injury ...Guidelines (BIG) are a classification tool for stratifying patients into injury severity and risk-of-progression categories based on presenting clinical and radiographic findings. In the present study, the authors aimed to validate BIG criteria at a single level 1 trauma center.
Patients were classified according to BIG criteria and evaluated for subsequent radiographic progression or development of neurological decline. A 2-year retrospective cohort review of consecutive patients with neurotrauma (n = 590) was undertaken. The authors then developed a modified BIG algorithm for use at their institution and followed its implementation prospectively over 555 consecutive patients.
In the retrospective analysis, no patient in the BIG 1 category (n = 88, 14.9%) demonstrated progression or neurological decline, and 7.5% of BIG 2 patients (n = 107, 18.1%) demonstrated mild radiographic progression without any decline or need for additional neurosurgical or medical intervention, whereas 15.4% of BIG 3 patients (n = 395, 66.9%) underwent additional neurosurgical procedures. In the prospective analysis, no BIG 1 (n = 105, 18.9%) or BIG 2 (n = 48, 8.6%) patients demonstrated a clinical decline or required any further neurosurgical intervention. By contrast, 12.9% of BIG 3 patients (n = 402, 72%) required immediate neurosurgical intervention, and a further 2.0% required delayed intervention based on clinical and/or radiographic evidence of injury progression.
Application of the BIG criteria in a single large level 1 trauma center reliably sorted patients into appropriate risk categories that accurately guided ongoing management.
The pathophysiology of trigeminal neuralgia (TN) in patients without neurovascular compression (NVC) is not completely understood. The objective of this retrospective study was to evaluate the ...hypothesis that TN patients without NVC differ from TN patient with NVC with respect to brain anatomy and demographic characteristics.
Six anatomical brain measurements from high-resolution brain MR images were tabulated; anterior-posterior (AP) prepontine cistern length, cerebellopontine angle (CPA) cistern volume, nerve-to-nerve distance, symptomatic nerve length, pons volume, and posterior fossa volume were assessed on OsiriX. Brain MRI anatomical measurements from 232 patients with either TN type 1 or TN type 2 (TN group) were compared with measurements obtained in 100 age- and sex-matched healthy controls (control group). Two-way ANOVA tests were conducted on the 6 measurements relative to group and NVC status. Bonferroni adjustments were used to correct for multiple comparisons. A nonhierarchical k-means cluster analysis was performed on the TN group using age and posterior fossa volume as independent variables.
Within the TN group, females were found to be younger than males and less likely to have NVC. The odds ratio (OR) of females not having NVC compared to males was 2.7 (95% CI 1.3-5.5, p = 0.017). Patients younger than 30 years were much less likely to have NVC compared to older patients (OR 4.9, 95% CI 1.3-18.4, p = 0.017). The mean AP prepontine cistern length and symptomatic nerve length were smaller in the TN group than in the control group (5.3 vs 6.5 mm and 8.7 vs 9.7 mm, respectively; p < 0.001). The posterior fossa volume was significantly smaller in TN patients without NVC compared to those with NVC. A TN group cluster analysis suggested a sex-dependent difference that was not observed in those without NVC. Factorial ANOVA and post hoc testing found that findings in males without NVC were significantly different from those in controls or male TN patients with NVC and similar to those in females (female controls as well as female TN patients with or without NVC).
Posterior fossa volume in males was larger than posterior fossa volume in females. This finding, along with the higher incidence of TN in females, suggests that smaller posterior fossa volume might be an independent factor in the pathophysiology of TN, which warrants further study.
The combination of liquid chromatography coupled to high resolution mass spectrometry (LC-HRESMS)-based dereplication and antiproliferative activity-guided fractionation was applied on the Red ...Sea-derived soft coral
sp. This approach facilitated the isolation of five new cembrane-type diterpenoids (
-
), along with two known analogs (
and
), as well as the identification of 19 further, known compounds. The chemical structures of the new compounds were elucidated while using comprehensive spectroscopic analyses, including one-dimensional (1D) and two-dimensional (2D) NMR and HRMS. All of the isolated cembranoids (
-
) showed moderate
antiproliferative activity against a human breast cancer cell line (MCF-7), with IC
ranging from 22.39-27.12 µg/mL. This class of compounds could thus serve as scaffold for the future design of anticancer leads.
Abstract To systematically review and conduct a meta-analysis to evaluate the safety and efficacy of the unilateral focused ultrasound (FUS) pallidotomy on motor complications in Parkinson’s disease ...(PD) patients. A comprehensive search strategy was implemented through August 15, 2023, and updated on February 13, 2024, across six databases, identifying studies relevant to unilateral focused ultrasound pallidotomy and PD. Eligibility criteria included observational studies, clinical trials, and case series reporting on the impact of the intervention on motor complications in PD patients. The screening and data extraction were done by two independent reviewers. Risk of bias assessment utilized appropriate tools for different study designs. Statistical analysis involved narrative synthesis and meta-analysis. Subgroup analyses and leave-one-out analyses were performed. Five studies were included in our study, involving 112 PD patients undergoing FUS pallidotomy. UPDRS-II analysis revealed a significant improvement from baseline (mean difference (MD): -3.205, 95% CI: -4.501, -1.909, P < 0.001). UPDRS-III overall change was significant (MD: -10.177, 95% CI: -12.748, -7.606, P < 0.001). UPDRS-IV showed a significant change from baseline (MD: -5.069, 95% CI: -5.915, -4.224, P < 0.001). UDysRS demonstrated a significant overall improvement (MD: -18.895, 95% CI: -26.973, -10.818, P < 0.001). The effect of FUS pallidotomy on motor complications in PD patients was effective, with a significant decrease in the UPDRS and UDysRS, reflecting improvement. The incidence of adverse events (headaches, pin-site pain, difficulty walking, and sonication-related head pain) of the FUS pallidotomy was not statistically significant, indicating its safety.
The author presents data to support the continued need for ablative procedures, particularly cordotomy, in the management of cancer-related pain.
Fifty-one patients with cancer-related body or face ...pain were treated with computed tomography-guided radiofrequency ablation of the spinothalamic tract or trigeminal tract nucleus in the upper cervical region of the spinal cord. Forty-one patients underwent a unilateral cervical cordotomy, and 10 patients underwent a trigeminal tractotomy-nucleotomy. Three methods to assess patient pain were used: degree of pain relief, Visual Analog Scale, and total sleeping hours. The Karnofsky scale was used to measure the patient's level of function pre- and postprocedure.
After surgical intervention, patients reported initial and 6-months follow-up pain relief as 98 and 80%, respectively.
Computed tomography-guided ablation of the upper cervical spinal cord is a safe and effective procedure to treat cancer pain involving the body or face. There remains a need for ablative procedures, in particular cordotomy, in the management of cancer-related pain.
Abstract
BACKGROUND
Managing cancer pain once it is refractory to conventional treatment continues to challenge caregivers committed to serving those who are suffering from a malignancy. Although ...neuromodulation has a role in the treatment of cancer pain for some patients, these therapies may not be suitable for all patients. Therefore, neuroablative procedures, which were once a mainstay in treating intractable cancer pain, are again on the rise. This guideline serves as a systematic review of the literature of the outcomes following neuroablative procedures.
OBJECTIVE
To establish clinical practice guidelines for the use of neuroablative procedures to treat patients with cancer pain.
METHODS
A systematic review of neuroablative procedures used to treat patients with cancer pain from 1980 to April 2019 was performed using the United States National Library of Medicine PubMed database, EMBASE, and Cochrane CENTRAL. After inclusion criteria were established, full text articles that met the inclusion criteria were reviewed by 2 members of the task force and the quality of the evidence was graded.
RESULTS
In total, 14 646 relevant abstracts were identified by the literature search, from which 189 met initial screening criteria. After full text review, 58 of the 189 articles were included and subdivided into 4 different clinical scenarios. These include unilateral somatic nociceptive/neuropathic body cancer pain, craniofacial cancer pain, midline subdiaphragmatic visceral cancer pain, and disseminated cancer pain. Class II and III evidence was available for these 4 clinical scenarios. Level III recommendations were developed for the use of neuroablative procedures to treat patients with cancer pain.
CONCLUSION
Neuroablative procedures may be an option for treating patients with refractory cancer pain. Serious adverse events were reported in some studies, but were relatively uncommon. Improved imaging, refinements in technique and the availability of new lesioning modalities may minimize the risks of neuroablation even further.
The full guidelines can be accessed at https://www.cns.org/guidelines/browse-guidelines-detail/guidelines-on-neuroablative-procedures-patients-wi.
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•Piracetam mitigates cisplatin induced nephrotoxicity.•Piracetam improved renal morphology and biochemical parameters of renal function.•Piracetam modulates oxidative stress, ...inflammation andapoptosis.•Piracetam modulated molecular pathways regulated byAMPK.
Cisplatin (CDDP) is commonly employed as an antineoplastic agent, but its use is significantly limited by the occurrence of dose-dependent nephrotoxicity, the detailed mechanisms of which remain unclear. This research is aimed to explore the molecular mechanisms of Piracetam (PIR)’s protective effects on nephrotoxicity resulting from CDDP exposure and to elucidate the mechanisms responsible for these effects.
PIR was given in dosages of 100 and 300 mg/kg body weight for a duration of 15 days; concurrently, on the last day, a single 10 mg/kg dose of CDDP was delivered via intraperitoneal injection. Forty-eight hours post-CDDP injection, the animals were sacrificed to assess nephrotoxicity. Blood samples and renal tissues were taken for biochemical and histopathological investigations. Serum creatinine and blood urea nitrogen (BUN) were measured. AMP-activated protein kinase (AMPK), caspase-9 and nuclear factor kappa b p65 (NF-κB p65) were assessed by immunohistochemistry method. Enzyme-linked immunosorbent assay (ELISA) analysis was employed to determine cytochrome c (Cyt. c), Bcl-2-associated X-protein (BAX), caspase-3, nuclear factor erythroid 2–related factor 2 (Nrf2), Heme oxygenase-1 (HO-1), superoxide dismutase (SOD), tumor necrosis factor alpha (TNF-α), myeloperoxidase (MPO), and interleukin-1β (IL-1β) levels in renal tissue homogenates. The mRNA levels of tumor protein P53 (TP53), phosphatidylinositol-3 kinase (PI3K), protein kinase B (Akt), p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinases (ERK), and c-Jun N-terminal kinases (JNK) were tested by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, histopathological evaluations of the renal tissues and the binding affinity of PIR to AMPK by molecular docking were also performed.
Pre-treatment with PIR enhanced renal function markers such as urea and creatinine, mitigated histological damage, and diminished inflammatory cell presence in renal tubules. PIR demonstrated antioxidant effects by reestablishing the equilibrium between pro-oxidants and antioxidants such as MPO, HO-1, Nrf2, as well as SOD. Furthermore, PIR inhibited the inflammatory pathways through the MAPK/NF-κB pathway. Additionally, PIR counteracted the CDDP-induced decline in PI3K/Akt activity and hindered caspase-dependent apoptotic processes.
In summary, PIR appears to be an effective therapeutic strategy for reducing CDDP-induced nephrotoxicity, attributed to its antioxidant, anti-inflammatory, and antiapoptotic mechanisms. Consequently, PIR may serve as a complementary treatment alongside CDDP to alleviate nephrotoxicity associated with CDDP.
Abstract Tamoxifen (TAM) is a key player in estrogen receptor-positive (ER+) breast cancer (BC); however, ∼30% of patients experience relapse and a lower survival rate due to TAM resistance. TAM ...resistance was related to the over expression of SOX-2 gene, which is regulated by the E2F3 transcription factor in the Wnt signaling pathway. It was suggested that SOX-2 overexpression was suppressed by dexamethasone (DEX), a glucocorticoid commonly prescribed to BC patients. The aim of the present study is to explore the effect of combining DEX and TAM on the inhibition of TAM-resistant LCC-2 cells (TAMR-1) through modulating the E2F3/SOX-2-mediated Wnt signaling pathway. The effect of the combination therapy on MCF-7 and TAMR-1 cell viability was assessed. Drug interactions were analyzed using CompuSyn and SynergyFinder softwares. Cell cycle distribution, apoptotic protein expression, gene expression levels of SOX-2 and E2F3, and cell migration were also assessed. Combining DEX with TAM led to synergistic inhibition of TAMR-1 cell proliferation and migration, induced apoptosis, reduced SOX-2 and E2F3 expression and was also associated with S and G2-M phase arrest. Therefore, combining DEX with TAM may present an effective therapeutic option to overcome TAM resistance, by targeting the E2F3/SOX-2/Wnt signaling pathway, in addition to its anti-inflammatory effect.
Previous electrophysiological research has characterized canonical oscillatory patterns associated with movement mostly from recordings of primary sensorimotor cortex. Less work has attempted to ...decode movement based on electrophysiological recordings from a broader array of brain areas such as those sampled by stereoelectroencephalography (sEEG), especially in humans. We aimed to identify and characterize different movement-related oscillations across a relatively broad sampling of brain areas in humans and if they extended beyond brain areas previously associated with movement.
We used a linear support vector machine to decode time-frequency spectrograms time-locked to movement, and we validated our results with cluster permutation testing and common spatial pattern decoding.
We were able to accurately classify sEEG spectrograms during a keypress movement task versus the inter-trial interval. Specifically, we found these previously-described patterns: beta (13-30 Hz) desynchronization, beta synchronization (rebound), pre-movement alpha (8-15 Hz) modulation, a post-movement broadband gamma (60-90 Hz) increase and an event-related potential. These oscillatory patterns were newly observed in a wide range of brain areas accessible with sEEG that are not accessible with other electrophysiology recording methods. For example, the presence of beta desynchronization in the frontal lobe was more widespread than previously described, extending outside primary and secondary motor cortices.
Our classification revealed prominent time-frequency patterns which were also observed in previous studies that used non-invasive electroencephalography and electrocorticography, but here we identified these patterns in brain regions that had not yet been associated with movement. This provides new evidence for the anatomical extent of the system of putative motor networks that exhibit each of these oscillatory patterns.
The lumbar drain exit site purse string oversew stitch is a well-described bedside intervention to stop or prevent cerebrospinal fluid (CSF) leak. It is not routinely placed at the time of lumbar ...drain placement. Via four plan-do-study-act (PDSA) cycles, we test the effect of prophylactic utilization of the lumbar drain exit site oversew stitch on house officers' paging burden, need to redress the drain, need to oversew the drain to stop a CSF leak, and need to replace the drain. We found that the simple act of placing an oversew stitch at the time of lumbar drain placement significantly reduced paging burden and reduced the frequency at which an oversew stitch was required to stop a CSF leak. Subjectively, during PDSA cycles during which overstitches were placed prophylactically, in-house residents perceived that there were less lumbar drains on service, although objectively, the overall number was unchanged. We conclude that prophylactic lumbar drain exit site stitch placement reduces risk and bedside interventions for patients and also reduces overall call burden on house officers. This simple intervention may therefore provide a more widespread improvement in care quality beyond lumbar drain care because house officers experience less burnout during their call shifts.
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