Glioma.

Gliomas are primary brain tumours that are thought to develop from neural stem or progenitor cells that carry tumour-initiating genetic alterations. Based on microscopic appearance and molecular characteristics, they are classified according to the WHO classification of central nervous system (CNS) tumours and graded into CNS WHO grades 1-4 from a low to high grade of malignancy. Diffusely infiltrating gliomas in adults comprise three tumour types with distinct natural course of disease, response to treatment and outcome: isocitrate dehydrogenase (IDH)-mutant and 1p/19q-codeleted oligodendrogliomas with the best prognosis; IDH-mutant astrocytomas with intermediate outcome; and IDH-wild-type glioblastomas with poor prognosis. Pilocytic astrocytoma is the most common glioma in children and is characterized by circumscribed growth, frequent BRAF alterations and favourable prognosis. Diffuse gliomas in children are divided into clinically indolent low-grade tumours and high-grade tumours with aggressive behaviour, with histone 3 K27-altered diffuse midline glioma being the leading cause of glioma-related death in children. Ependymal tumours are subdivided into biologically and prognostically distinct types on the basis of histology, molecular biomarkers and location. Although surgery, radiotherapy and alkylating agent chemotherapy are the mainstay of glioma treatment, individually tailored strategies based on tumour-intrinsic dominant signalling pathways have improved outcome in subsets of patients.

Impact of Posterior Wall Isolation During AF Ablation on the Incidence of Left Atrial Flutter.

BACKGROUND: Linear and complex electrogram ablation (LCEA) beyond pulmonary vein isolation (PVI) is associated with an increase in left atrial macro-re-entrant tachycardias (LAMTs). Posterior wall isolation (PWI) is increasingly performed to improve AF ablation outcomes. However, the impact of PWI on the incidence of LAMT is unknown. OBJECTIVES: The purpose of this study was to establish the incidence of LAMT following PVI alone vs PVI + PWI vs PVI + PWI + LCEA. METHODS: Consecutive patients undergoing catheter ablation for AF or LAMT post-AF ablation between 2008 and 2022 from 4 electrophysiology centers were reviewed with a minimum follow-up of 12 months. RESULTS: In total, 5,619 (4,419 index, 1,100 redo) AF ablation procedures were performed in 4,783 patients (mean age 60.9 ± 10.6 years, 70.7% men). Over a mean follow-up of 6.4 ± 3.8 years, 246 procedures for LAMT were performed in 214 patients at a mean of 2.6 ± 0.6 years post-AF ablation. Perimitral (52.8% of patients), roof-dependent (27.1%), PV gap-related (17.3%), and anterior circuits (8.9%) were most common, with 16.4% demonstrating multiple circuits. The incidence of LAMT was significantly higher following PVI + PWI (6.2%) vs PVI alone (3.0%; P < 0.0001) and following PVI + PWI + LCEA vs PVI + PWI (12.5%; P = 0.019). Conduction gaps in previous ablation lines were responsible for LAMT in 28.4% post-PVI alone, 35.3% post-PVI + PWI (P = 0.386), and 81.8% post-PVI + PWI + LCEA (P < 0.005). CONCLUSIONS: The incidence of LAMT following PVI + PWI is higher than with PVI alone but significantly lower than with more extensive atrial substrate modification. Given a low frequency of LAMT following PWI, empiric mitral isthmus ablation is not justified and may be proarrhythmic.

External assessment of preoperative scores for predicting outcome after microvascular decompression for trigeminal neuralgia.

OBJECTIVE: Recently, two scoring systems have been developed for predicting pain-free outcomes after microvascular decompression (MVD). Evaluation of these scores on large external datasets has been limited. In this study, the authors aimed to evaluate the performance of published MVD scoring systems in predicting pain-free outcome. METHODS: A total of 458 patients who underwent MVD for trigeminal neuralgia (TN) between 2007 and 2020 and had at least 6 months of follow-up were included in this study. Hardaway and Panczykowski scores were retrospectively computed for each patient and compared with postoperative pain recurrence and pain-free duration. RESULTS: The mean ± SD area under the receiver operating characteristic curve for predicting any pain recurrence after MVD was 0.567 ± 0.081 using the Hardaway score and 0.546 ± 0.085 using the Panczykowski score. On log-rank tests and Kaplan-Meier analysis, the patients with Hardaway scores of 0-2 had significantly shorter pain-free survival times after MVD than did those with a score of 3. Patients with a Panczykowski score of 1 had a significantly shorter pain-free duration after surgery compared with both patients with scores of 2-3 and patients with scores of 4-5. Patients with Panczykowski scores of 2-3 also had significantly shorter pain-free duration compared with patients with scores of 4-5. CONCLUSIONS: Both the Hardaway and Panczykowski scores may be useful for predicting postoperative pain-free duration in TN patients, and their utility may be greatest when scores are clustered. Continued refinement of both scoring systems will help to improve our ability to predict patient outcomes after MVD.

Intra- and post-pandemic impact of the COVID-19 outbreak on Stanford Health Care.

Stanford Health Care, which provides about 7% of overall healthcare to approximately 9 million people in the San Francisco Bay Area, has undergone significant changes due to the opening of a second hospital in late 2019 and, more importantly, the COVID-19 pandemic. We examine the impact of these events on anatomic pathology (AP) cases, aiming to enhance operational efficiency in response to evolving healthcare demands. We extracted historical census, admission, lab tests, operation, and AP data since 2015. An approximately 45% increase in the volume of laboratory tests (P < 0.0001) and a 17% increase in AP cases (P < 0.0001) occurred post-pandemic. These increases were associated with progressively increasing (P < 0.0001) hospital census. Census increase stemmed from higher admission through the emergency department (ED), and longer lengths of stay mostly for transfer patients, likely due to the greater capability of the new ED and changes in regional and local practice patterns post-pandemic. Higher census led to overcapacity, which has an inverted U relationship that peaked at 103% capacity for AP cases and 114% capacity for laboratory tests. Overcapacity led to a lower capability to perform clinical activities, particularly those related to surgical procedures. We conclude by suggesting parameters for optimal operations in the post-pandemic era.

CCR2 and CCR5 co-inhibition modulates immunosuppressive myeloid milieu in glioma and synergizes with anti-PD-1 therapy.

Immunotherapy has revolutionized the treatment of cancers. Reinvigorating lymphocytes with checkpoint blockade has become a cornerstone of immunotherapy for multiple tumor types, but the treatment of glioblastoma has not yet shown clinical efficacy. A major hurdle to treat GBM with checkpoint blockade is the high degree of myeloid-mediated immunosuppression in brain tumors that limits CD8 T-cell activity. A potential strategy to improve anti-tumor efficacy against glioma is to use myeloid-modulating agents to target immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. We found that the co-inhibition of the chemokine receptors CCR2 and CCR5 in murine model of glioma improves the survival and synergizes robustly with anti-PD-1 therapy. Moreover, the treatment specifically reduced the infiltration of monocytic-MDSCs (M-MDSCs) into brain tumors and increased lymphocyte abundance and cytokine secretion by tumor-infiltrating CD8 T cells. The depletion of T-cell subsets and myeloid cells abrogated the effects of CCR2 and CCR5 blockade, indicating that while broad depletion of myeloid cells does not improve survival, specific reduction in the infiltration of immunosuppressive myeloid cells, such as M-MDSCs, can boost the anti-tumor immune response of lymphocytes. Our study highlights the potential of CCR2/CCR5 co-inhibition in reducing myeloid-mediated immunosuppression in GBM patients.

Preoperative Opioid Use and Postoperative Outcomes in Patients Undergoing Microvascular Decompression for Trigeminal Neuralgia.

BACKGROUND AND OBJECTIVES: The prescription of opioid analgesics for trigeminal neuralgia (TN) is controversial, and their effect on postoperative outcomes for patients with TN undergoing microvascular decompression (MVD) has not been reported. We aimed to describe the relationship between preoperative opioid use and postoperative outcomes in patients with TN undergoing MVD. METHODS: We reviewed the records of 920 patients with TN at our institution who underwent an MVD between 2007 and 2020. Patients were sorted into 2 groups based on preoperative opioid usage. Demographic information, comorbidities, characteristics of TN, preoperative medications, pain and numbness outcomes, and recurrence data were recorded and compared between groups. Multivariate ordinal regression, Kaplan-Meier survival analysis, and Cox proportional hazards were used to assess differences in pain outcomes between groups. RESULTS: One hundred and forty-five (15.8%) patients in this study used opioids preoperatively. Patients who used opioids preoperatively were younger (P = .04), were more likely to have a smoking history (P < .001), experienced greater pain in modified Barrow Neurological Institute pain score at final follow-up (P = .001), and were more likely to experience pain recurrence (P = .01). In addition, patients who used opioids preoperatively were more likely to also have been prescribed TN medications including muscle relaxants and antidepressants preoperatively (P < .001 and P < .001, respectively). On multivariate regression, opioid use was an independent risk factor for greater postoperative pain at final follow-up (P = .006) after controlling for variables including female sex and age. Opioid use was associated with shorter time to pain recurrence on Kaplan-Meier analysis (P = .005) and was associated with increased risk for recurrence on Cox proportional hazards regression (P = .008). CONCLUSION: Preoperative opioid use in the setting of TN is associated with worse pain outcomes and increased risk for pain recurrence after MVD. These results indicate that opioids should be prescribed cautiously for TN and that worse post-MVD outcomes may occur in patients using opioids preoperatively.

Adult neuro-oncology trials in the United States over 5 decades: Analysis of trials completion rate to guide the path forward.

Background: Clinical trials are important to close the gap between therapeutic unmet needs and scientific advances in neuro-oncology. This study analyzes the landscape of neuro-oncology trials to identify completion rates and guide strategies for the path forward. Methods: US-registered adult neuro-oncology clinical trials were extracted from www.clinicaltrials.gov (1966-2019), including funding source, trial type, scope, phase, and subjects' demographics. Completed trials defined as those that had completed participants' examinations or intervention administration for the purpose of the final collection of data for the primary outcome were dichotomized against those that failed to reach completion. Univariate and multivariate analyses were used to detect differences across factors comparing the last 2 decades (2000-2009, 2010-2019). Results: Our search yielded 4522 trials, of which 1257 are eligible for this study. In 25 US states, neuro-oncology trial availability is <0.85/100,000 population. Comparing the past 2 decades, trial completion rate decreased from 88% to 64% (P < .001) and National Institutes of Health funding decreased from 47% to 24% (P < .001). Inclusion of subjects >65-year-old and women increased, while inclusion of Hispanic subjects decreased (P < .001). The top 2 reasons for lack of completion included accrual and operational difficulties. A larger proportion of women, non-Hispanic subjects, and older adults were enrolled in completed trials than in those that failed completion. Conclusions: Our study is the first report on the neuro-oncology clinical trial landscape in the United States and supports the development of strategies to further improve access to these trials. Additionally, attention is needed to identify and modify other factors contributing to lack of completion.

Soluble PD-L1 reprograms blood monocytes to prevent cerebral edema and facilitate recovery after ischemic stroke.

Acute cerebral ischemia triggers a profound inflammatory response. While macrophages polarized to an M2-like phenotype clear debris and facilitate tissue repair, aberrant or prolonged macrophage activation is counterproductive to recovery. The inhibitory immune checkpoint Programmed Cell Death Protein 1 (PD-1) is upregulated on macrophage precursors (monocytes) in the blood after acute cerebrovascular injury. To investigate the therapeutic potential of PD-1 activation, we immunophenotyped circulating monocytes from patients and found that PD-1 expression was upregulated in the acute period after stroke. Murine studies using a temporary middle cerebral artery (MCA) occlusion (MCAO) model showed that intraperitoneal administration of soluble Programmed Death Ligand-1 (sPD-L1) significantly decreased brain edema and improved overall survival. Mice receiving sPD-L1 also had higher performance scores short-term, and more closely resembled sham animals on assessments of long-term functional recovery. These clinical and radiographic benefits were abrogated in global and myeloid-specific PD-1 knockout animals, confirming PD-1+ monocytes as the therapeutic target of sPD-L1. Single-cell RNA sequencing revealed that treatment skewed monocyte maturation to a non-classical Ly6Clo, CD43hi, PD-L1+ phenotype. These data support peripheral activation of PD-1 on inflammatory monocytes as a therapeutic strategy to treat neuroinflammation after acute ischemic stroke.

Management outcomes of peripontine arteriovenous malformation patients presenting with trigeminal neuralgia.

OBJECTIVE: Trigeminal neuralgia as the presenting symptom of brain arteriovenous malformation (bAVM) has been rarely reported. Treatment of reported cases has been skewed toward surgery for these scarce, deeply located bAVMs. Here, the authors report their management and outcomes of bAVM patients presenting with ipsilateral trigeminal neuralgia (TN) at their institution. METHODS: This is a retrospective cohort study. The authors' institutional bAVM database was queried for non-hereditary hemorrhagic telangiectasia bAVMs in pontine, cistern, brainstem, trigeminal nerve, or tentorial locations. Patients with complete data were included in a search for trigeminal neuralgia or "facial pain" as the presenting symptom with TN being on the same side as the bAVM. Demographics, TN and bAVM characteristics, management strategies, and outcomes of bAVM and TN management were analyzed. RESULTS: Fifty-seven peripontine bAVMs were identified; 8 (14.0%) of these bAVMs were discovered because of ipsilateral TN, including 4 patients (50%) with facial pain in the V2 distribution. Five patients (62.5%) were treated with carbamazepine as the initial medical therapy, 2 (25%) underwent multiple rhizotomies, and 1 (12.5%) underwent microvascular decompression. None of the patients with TN-associated bAVMs presented with hemorrhage, compared with 25 patients (51%) with bAVMs that were not associated with TN (p < 0.01). TN-associated bAVMs were overall smaller than non-TN-associated bAVMs, but the difference was not statistically significant (1.71 cm vs 2.22 cm, p = 0.117), and the Spetzler-Martin grades were similar. Six patients (75%) underwent radiosurgery to the bAVM (mean dose 1800 cGy, mean target volume 0.563 cm3) and had complete resolution of TN symptoms (100%). The mean time from radiosurgery to TN resolution was 193 (range 21-360) days, and 83.3% of treated TN-associated bAVMs were obliterated via radiosurgery. Two patients (12.5%) were recommended for conservative management, with one undergoing subsequent rhizotomies and another patient died of hemorrhage during follow-up. CONCLUSIONS: TN-associated bAVM is a rare condition with limited evidence for management guidance. Radiosurgery can be safe and effective in achieving durable TN control in patients with TN-associated bAVMs. Despite their deep location and unruptured presentation, obliteration can reach 83.3% with radiosurgery.

Application of a Clinical Approach to Diagnosing Primary Pain: Prevalence and Correlates of Primary Back and Neck Pain in a Community Physiatry Clinic.

Chronic back or neck pain (CBNP) can be primary (nociplastic or neuroplastic; without clear peripheral etiology) or secondary (to nociceptive or neuropathic causes). Expanding on available models of nociplastic pain, we developed a clinic-ready approach to diagnose primary/nociplastic pain: first, a standard physical exam and review of imaging to rule out secondary pain; and second, a detailed history of symptom presentation to rule in primary pain. We trained a physician who evaluated 222 patients (73.9% female, age M = 59.6) with CBNP; patients separately completed pain and psychosocial questionnaires. We estimated the prevalence of primary CBNP and explored biomedical, imaging, and psychological correlates of primary CBNP. Although almost all patients (97.7%) had at least 1 spinal anomaly on imaging, the diagnostic approach estimated that 88.3% of patients had primary pain, 5.0% had secondary pain, and 6.8% had mixed pain. Patients with primary pain were more likely than the other 2 groups of patients (combined as "non-primary pain") to report certain functional conditions, central sensitization, and features such as sensitivity to light touch, spreading pain, and pain worsening with stress; however, no difference was detected in depression, anxiety, and pain catastrophizing between those with primary and nonprimary pain. These findings are consistent with prior estimates that 85 to 90% of CBNP is "nonspecific." Further research is needed to validate and perhaps refine this diagnostic approach, which holds the potential for better outcomes if patients are offered treatments targeted to primary pain, such as pain neuroscience education and several emerging psychological therapies. PERSPECTIVE: We developed an approach to diagnose chronic primary pain, which was applied in a physiatry clinic to 222 patients with CBNP. Most patients (88.3%) had primary pain, despite almost universal anomalies on spinal imaging. This diagnostic approach can guide educational and psychological treatments tailored for primary pain.

Proteomic Analysis to Identify Prospective Biomarkers of Treatment Outcome After Microvascular Decompression for Trigeminal Neuralgia: A Preliminary Study.

Trigeminal neuralgia (TN) is a severe neuropathic facial pain disorder, often caused by vascular or neuronal compression of the trigeminal nerve. In such cases, microvascular decompression (MVD) surgery can be used to treat TN, but pain relief is not guaranteed. The molecular mechanisms that affect treatment response to MVD are not well understood. In this exploratory study, we performed label-free quantitative proteomic profiling of plasma and cerebrospinal fluid samples from patients undergoing MVD for TN, then compared the proteomic profiles of patients graded as responders (n = 7) versus non-responders (n = 9). We quantified 1,090 proteins in plasma and 1,087 proteins in the cerebrospinal fluid, of which 12 were differentially regulated in the same direction in both sample types. Functional analyses of differentially regulated proteins in protein-protein interaction networks suggested pathways of the immune system, axon guidance, and cellular stress response to be associated with response to MVD. These findings suggest potential biomarkers of response to MVD, as well as possible mechanisms of variable treatment success in TN patients. PERSPECTIVE: This exploratory study evaluates proteomic profiles in plasma and cerebrospinal fluid of patients undergoing microvascular decompression surgery for trigeminal neuralgia. Differential expression of proteins between surgery responders versus non-responders may serve as biomarkers to predict surgical success and provide insight into surgical mechanisms of pain relief in trigeminal neuralgia.

The influence of prior percutaneous rhizotomy on outcomes following microvascular decompression for trigeminal neuralgia.

OBJECTIVE: Microvascular decompression (MVD) is an effective intervention in patients with trigeminal neuralgia (TN). How prior rhizotomy can impact long-term pain outcomes following MVD is not well understood. In this study, the authors sought to compare pain outcomes in patients who had undergone primary MVD versus those who had undergone secondary MVD after a single or multiple rhizotomies. METHODS: The authors retrospectively reviewed the data on all patients who had undergone MVD at their institution from 2007 to 2020. Patients were included in the study if they had undergone primary MVD or if their surgical history was notable for past rhizotomy. Barrow Neurological Institute (BNI) pain scores were assigned at preoperative and final follow-up appointments. Perioperative complications were noted for each patient, and evidence of pain recurrence was recorded as well. A history of rhizotomy as well as other variables that might influence TN pain recurrence were evaluated using a Cox proportional hazards model. The impact of prior rhizotomy on TN pain recurrence following MVD was further assessed using Kaplan-Meier survival analysis. RESULTS: Of 1044 patients reviewed, 947 met the study inclusion criteria. Of these, 796 patients had undergone primary MVD, 84 had a history of a single rhizotomy before MVD, and 67 had a history of ≥ 2 rhizotomies prior to MVD. Patients in the single rhizotomy and multiple rhizotomies cohorts exhibited a greater frequency of preoperative numbness (p < 0.001), higher preoperative BNI pain scores (p < 0.005), and higher rates of postoperative numbness (p = 0.04). However, final follow-up BNI pain scores were not significantly different between the primary MVD and prior rhizotomy groups (p = 0.34). Cox proportional hazards analysis revealed that younger age, multiple sclerosis, and female sex independently predicted an increased risk of pain recurrence following MVD. Neither a history of a single prior rhizotomy nor a history of multiple prior rhizotomies independently increased the risk of pain recurrence. Furthermore, Kaplan-Meier analysis of pain-free survival among the 3 groups revealed no relationship between a history of prior rhizotomy and pain recurrence following MVD (p = 0.57). CONCLUSIONS: Percutaneous rhizotomy does not complicate outcomes following subsequent MVD for TN pain. However, patients undergoing rhizotomy before MVD may have an increased risk of postoperative facial numbness compared to that in patients undergoing primary MVD.

Stanford University School of Medicine: Our Neurosurgical Heritage.

The legacy of Stanford University's Department of Neurosurgery began in 1858, with the establishment of a new medical school on the West Coast. Stanford Neurosurgery instilled an atmosphere of dedication to neurosurgical care, scientific research, education, and innovation. We highlight key historical events leading to the formation of the medical school and neurosurgical department, the individuals who shaped the department's vision and expansion, as well as pioneering advances in research and clinical care. The residency program was started in 1961, establishing the basis of the current education model with a strong emphasis on training future leaders, and the Moyamoya Center, founded in 1991, became the largest Moyamoya referral center in the United States. The opening of Stanford Stroke Center (1992) and seminal clinical trials resulted in a significant impact on cerebrovascular disease by expanding the treatment window of IV thrombolysis and intra-arterial thrombectomy. The invention and implementation of CyberKnife® (1994) marks another important event that revolutionized the field of radiosurgery, and the development of Stanford's innovative Brain Computer Interface program is pushing the boundaries of this specialty. The more recent launch of the Neurosurgery Virtual Reality and Simulation Center (2017) exemplifies how Stanford is continuing to evolve in this ever-changing field. The department also became a model for diversity within the school as well as nationwide. The growth of Stanford Neurosurgery from one of the youngest neurosurgery departments in the country to a prominent comprehensive neurosurgery center mirrors the history of neurosurgery itself: young, innovative, and willing to overcome challenges.

Neurovascular Compression in Patients With Trigeminal Neuralgia May Be Associated With Worse Outcomes After Primary Percutaneous Rhizotomy.

BACKGROUND AND OBJECTIVES: Percutaneous rhizotomy may be an effective primary intervention in patients with trigeminal neuralgia who are poor candidates for microvascular decompression or those who desire a less invasive approach. However, the influence of neurovascular compression on pain-free survival after primary percutaneous rhizotomy is not well understood. METHODS: We retrospectively reviewed all patients undergoing percutaneous rhizotomy at our institution from 1995 to 2022. Patients were included if they had no history of surgical intervention, available preoperative MRI imaging, and postoperative follow-up data. Barrow Neurological Institute pain scores were assigned at various time points. We collected baseline patient information, pain characteristics, and perioperative complications for each patient. In addition, we recorded evidence of pain recurrence. Patients were dichotomized into those with evidence of neurovascular compression on preoperative MRI vs those without. The effect of neurovascular compression on pain-free survival was assessed using Kaplan-Meier Cox proportional hazards analyses. RESULTS: Of the 2726 patients reviewed, 298 met our inclusion criteria. Our study comprised 261 patients with no evidence of neurovascular compression on preoperative MRI vs 37 patients with evidence of neurovascular compression on preoperative MRI. Patients in the compression group had a shorter median duration to recurrence compared with those in the no compression group, P = .01. Kaplan-Meier survival analysis revealed that patients with preoperative evidence of neurovascular compression on MRI imaging demonstrated shorter pain-free survival compared with those without such evidence [hazard ratio = 1.57 (1.03-2.4), P = .037]. Cox proportional hazards analysis demonstrated that evidence of neurovascular compression was associated with poor pain-free survival [hazard ratio = 1.64 (1.06-2.53), P = .03]. CONCLUSION: Patients with neurovascular compression on preoperative MRI may experience reduced time to recurrence compared with those without after percutaneous rhizotomy. These patients should be counseled on potential reduced efficacy of percutaneous rhizotomy as a primary intervention for their pain.

Early Utilization of Mechanical Circulatory Support in Acute Myocardial Infarction Complicated by Cardiogenic Shock: The National Cardiogenic Shock Initiative.

BACKGROUND: Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) is associated with significant morbidity and mortality. Mechanical circulatory support (MCS) devices increase systemic blood pressure and end organ perfusion while reducing cardiac filling pressures. METHODS AND RESULTS: The National Cardiogenic Shock Initiative (NCT03677180) is a single-arm, multicenter study. The purpose of this study was to assess the feasibility and effectiveness of utilizing early MCS with Impella in patients presenting with AMI-CS. The primary end point was in-hospital mortality. A total of 406 patients were enrolled at 80 sites between 2016 and 2020. Average age was 64±12 years, 24% were female, 17% had a witnessed out-of-hospital cardiac arrest, 27% had in-hospital cardiac arrest, and 9% were under active cardiopulmonary resuscitation during MCS implantation. Patients presented with a mean systolic blood pressure of 77.2±19.2 mm Hg, 85% of patients were on vasopressors or inotropes, mean lactate was 4.8±3.9 mmol/L and cardiac power output was 0.67±0.29 watts. At 24 hours, mean systolic blood pressure improved to 103.9±17.8 mm Hg, lactate to 2.7±2.8 mmol/L, and cardiac power output to 1.0±1.3 watts. Procedural survival, survival to discharge, survival to 30 days, and survival to 1 year were 99%, 71%, 68%, and 53%, respectively. CONCLUSIONS: Early use of MCS in AMI-CS is feasible across varying health care settings and resulted in improvements to early hemodynamics and perfusion. Survival rates to hospital discharge were high. Given the encouraging results from our analysis, randomized clinical trials are warranted to assess the role of utilizing early MCS, using a standardized, multidisciplinary approach.

The pathophysiology of trigeminal neuralgia: a molecular review.

OBJECTIVE: The goal of this study was to provide a comprehensive overview of the current understanding of molecular and genetic mechanisms underlying the pathophysiology of trigeminal neuralgia (TN). METHODS: The authors searched PubMed systematically for primary research literature investigating specific molecular mechanisms from samples derived from patients with TN. The genes/molecules of interest from the selected literature were then cross-referenced with corresponding studies in animal models of TN. RESULTS: From approximately 345 articles, a total of 12 articles were selected and included in the review, focusing on ionotropic channel expressivity and mutations, reactive oxygen species expressivity, inflammatory marker expressivity, and microRNA expressivity. Of the 12 included articles, only 4 had studies completed in other animal models regarding the corresponding TN mechanism found in humans. CONCLUSIONS: The current literature does not suggest a conclusive disease mechanism for TN in humans. In addition to neurovascular conflict/compression of the trigeminal nerve, recent studies have indicated that TN may be linked to inflammatory and reactive oxygen species signaling as well. Recent genetic studies in patients with TN have yet to be investigated further in animal models.

Frailty Predicts Worse Pain Outcomes for Older TN Patients Treated with Microvascular Decompression.

BACKGROUND: Trigeminal neuralgia (TN) is a debilitating orofacial pain disorder. Recent data from a national database suggest that microvascular decompression (MVD) in frail patients is associated with more postoperative complications. However, the long-term pain outcomes for frail TN patients are not known. We aimed to elucidate the relationship between frailty and long-term pain outcomes after MVD for TN. METHODS: From 2007 to 2020, 368 TN patients aged ≥60 years underwent MVD at our institution. Patient demographics, clinical characteristics, postoperative complications, and long-term pain outcomes were recorded. Frailty was assessed using the modified 5-item frailty index (mFI-5) score, and the patients were dichotomized into nonfrail (mFI-5 <2) and frail (mFI-5 >1). Differences were assessed via the t test, χ2 test, multivariate ordinal regression, and Cox proportional hazards analysis. RESULTS: Of the 368 patients analyzed, 9.8% were frail. The frail patients were significantly older (P = 0.02) with a higher body mass index (P = 0.01) and a greater incidence of comorbidities (P < 0.001). Frail patients presented with significantly higher pain levels at the final follow-up (P = 0.04). On multivariate analysis, frailty was independently associated with more pain at follow-up (P = 0.01), as was younger age, female sex, and black race. The relationship between frailty and postoperative pain recurrence showed a trend toward significance (P = 0.06), and younger age and black race were significantly associated with recurrence. CONCLUSIONS: Frail patients undergoing MVD are at risk of worse long-term pain outcomes. Our results provide clinicians with useful information pertaining to the influence of frailty on the long-term efficacy of MVD in treating TN.

Risk-stratified faecal immunochemical testing (FIT) for urgent colonoscopy in Lynch syndrome during the COVID-19 pandemic.

BACKGROUND: Lynch syndrome is a hereditary cancer disease resulting in an increased risk of colorectal cancer. Herein, findings are reported from an emergency clinical service implemented during the COVID-19 pandemic utilizing faecal immunochemical testing ('FIT') in Lynch syndrome patients to prioritize colonoscopy while endoscopy services were limited. METHODS: An emergency service protocol was designed to improve colonoscopic surveillance access throughout the COVID-19 pandemic in England for people with Lynch syndrome when services were extremely restricted (1 March 2020 to 31 March 2021) and promoted by the English National Health Service. Requests for faecal immunochemical testing from participating centres were sent to the National Health Service Bowel Cancer Screening South of England Hub and a faecal immunochemical testing kit, faecal immunochemical testing instructions, paper-based survey, and pre-paid return envelope were sent to patients. Reports with faecal haemoglobin results were returned electronically for clinical action. Risk stratification for colonoscopy was as follows: faecal haemoglobin less than 10 µg of haemoglobin/g of faeces (µg/g)-scheduled within 6-12 weeks; and faecal haemoglobin greater than or equal to 10 µg/g-triaged via an urgent suspected cancer clinical pathway. Primary outcomes of interest included the identification of highest-risk Lynch syndrome patients and determining the impact of faecal immunochemical testing in risk-stratified colonoscopic surveillance. RESULTS: Fifteen centres participated from June 2020 to March 2021. Uptake was 68.8 per cent amongst 558 patients invited. For 339 eligible participants analysed, 279 (82.3 per cent) had faecal haemoglobin less than 10 µg/g and 60 (17.7 per cent) had faecal haemoglobin greater than or equal to 10 µg/g. In the latter group, the diagnostic accuracy of faecal immunochemical testing was 65.9 per cent and escalation to colonoscopy was facilitated (median 49 versus 122 days, χ2 = 0.0003, P < 0.001). CONCLUSION: Faecal immunochemical testing demonstrated clinical value for Lynch syndrome patients requiring colorectal cancer surveillance during the pandemic in this descriptive report of an emergency COVID-19 response service. Further longitudinal investigation on faecal immunochemical testing efficacy in Lynch syndrome is warranted and will be examined under the 'FIT for Lynch' study (ISRCTN15740250).