Sub-region expression of brain-derived neurotrophic factor in the dorsal hippocampus and amygdala is Affected by mild traumatic brain injury and stress in male rats.

The US population suffers 1.5 million head injuries annually, of which mild traumatic brain injuries (mTBI) comprise 75%. Many individuals subsequently experience long-lasting negative symptoms, including anxiety. Previous rat-based work in our laboratory has shown that mTBI changes neuronal counts in the hippocampus and amygdala, regions associated with anxiety. Specifically, mTBI increased neuronal death in the dorsal CA1 sub-region of the hippocampus, but attenuated it in the medial (MeA) and the basolateral nuclei of the amygdala nine days following injury, which was associated with greater anxiety. We have also shown that glucocorticoid receptor (GR) antagonism prior to concomitant stress and mTBI extinguishes anxiety-like behaviors. Using immunohistochemistry, this study examines the expression of brain-derived neurotrophic factor (BDNF) following social defeat and mTBI, and whether this is affected by prior glucocorticoid receptor antagonism as a potential mechanism behind these anxiety and neuronal differences. Here, stress and mTBI upregulate BDNF in the MeA, and both GR and mineralocorticoid receptor antagonism downregulate BDNF in the dorsal hippocampal CA1 and dentate gyrus, as well as the central nucleus of the amygdala. These findings suggest BDNF plays a role in the mechanism underlying neuronal changes following mTBI in amygdalar and hippocampal subregions, and may participate in stress elicited changes to neural plasticity in these regions. Taken together, these results suggest an essential role for BDNF in the development of anxiety behaviors following concurrent stress and mTBI.

Pectoral Fascial Plane Versus Paravertebral Blocks for Minimally Invasive Mitral Valve Surgery Analgesia.

OBJECTIVES: This study examined the postoperative analgesic efficacy of single-injection pectoral fascial plane (PECS) II blocks compared to paravertebral blocks for elective robotic mitral valve surgery. DESIGN: A single-center retrospective study that reported patient and procedural characteristics, postoperative pain scores, and postoperative opioid use for patients undergoing robotic mitral valve surgery. SETTING: This investigation was performed at a large quaternary referral center. PARTICIPANTS: Adult patients (age ≥18) admitted to the authors' hospital from January 1, 2016, to August 14, 2020, for elective robotic mitral valve repair who received either a paravertebral or PECS II block for postoperative analgesia. INTERVENTIONS: Patients received an ultrasound-guided, unilateral paravertebral or PECS II nerve block. MEASUREMENTS AND MAIN RESULTS: One hundred twenty-three patients received a PECS II block, and 190 patients received a paravertebral block during the study period. The primary outcome measures were average postoperative pain scores and cumulative opioid use. Secondary outcomes included hospital and intensive care unit lengths of stay, need for reoperation, need for antiemetics, surgical wound infection, and atrial fibrillation incidence. Patients receiving the PECS II block required significantly fewer opioids in the immediate postoperative period than the paravertebral block group, and had comparable postoperative pain scores. No increase in adverse outcomes was noted for either group. CONCLUSIONS: The PECS II block is a safe and highly effective option for regional analgesia for robotic mitral valve surgery, with demonstrated efficacy comparable to the paravertebral block.

Hemodynamic course during ablation and selective hepatic artery embolization for metastatic liver carcinoid: a retrospective observational study.

BACKGROUND: Manipulation of carcinoid tumors during ablation or selective hepatic artery embolization (transarterial embolization, TAE) can release vasoactive mediators inducing hemodynamic instability. The main aim of our study was to review hemodynamics and complications related to minimally invasive treatments of liver carcinoids with TAE or ablation. METHODS: Electronic medical records of all patients with metastatic liver carcinoid undergoing ablation or TAE from 2003 to 2019 were abstracted. Noted were severe hypotension (mean arterial pressure [MAP] ..± 55.ßmmHg), severe hypertension (systolic blood pressure ... 180.ßmmHg), and perioperative complications. Associations of procedure type and pre-procedure octreotide use with intraprocedural hemodynamics were assessed using linear regression. A robust covariance approach using generalized estimating equation method was used to account for multiple observations. RESULTS: A total of 161 patients underwent 98 ablations and 207 TAEs. Severe hypertension was observed in 24 (24.5%) vs. 15 (7.3%), severe hypotension in 56 (57.1%) vs. 6 (2.9%), and cutaneous flushing observed in 2 (2.0%) vs. 48 (23.2%) ablations and TAEs, respectively. After adjusting for preprocedural MAP, ablation was associated with lower intraprocedural MAP compared to TAE (estimate -27.ßmmHg, 95%CI -30 to -24.ßmmHg, p.ß<.ß0.001). Intraprocedural declines in MAP were not affected by preprocedural use of octreotide (p.ß=.ß0.7 for TAE and p.ß=.ß0.4 for ablation). CONCLUSIONS: Ablation of liver carcinoids was associated with substantial hemodynamic instability, especially hypotension. In contrast, a higher number of TAE patients had cutaneous flushing. Preprocedural use of octreotide was not associated with attenuation of intraprocedural hypotension.

Hemodynamic course during ablation and selective hepatic artery embolization for metastatic liver carcinoid: a retrospective observational study

Abstract Background: Manipulation of carcinoid tumors during ablation or selective hepatic artery embolization (transarterial embolization, TAE) can release vasoactive mediators inducing hemodynamic instability. The main aim of our study was to review hemodynamics and complications related to minimally invasive treatments of liver carcinoids with TAE or ablation. Methods: Electronic medical records of all patients with metastatic liver carcinoid undergoing ablation or TAE from 2003 to 2019 were abstracted. Noted were severe hypotension (mean arterial pressure [MAP] ≤ 55 mmHg), severe hypertension (systolic blood pressure ≥ 180 mmHg), and perioperative complications. Associations of procedure type and pre-procedure octreotide use with intraprocedural hemodynamics were assessed using linear regression. A robust covariance approach using generalized estimating equation method was used to account for multiple observations. Results: A total of 161 patients underwent 98 ablations and 207 TAEs. Severe hypertension was observed in 24 (24.5%) vs. 15 (7.3%), severe hypotension in 56 (57.1%) vs. 6 (2.9%), and cutaneous flushing observed in 2 (2.0%) vs. 48 (23.2%) ablations and TAEs, respectively. After adjusting for preprocedural MAP, ablation was associated with lower intraprocedural MAP compared to TAE (estimate −27 mmHg, 95%CI −30 to −24 mmHg, p < 0.001). Intraprocedural declines in MAP were not affected by preprocedural use of octreotide (p = 0.7 for TAE and p = 0.4 for ablation). Conclusions: Ablation of liver carcinoids was associated with substantial hemodynamic instability, especially hypotension. In contrast, a higher number of TAE patients had cutaneous flushing. Preprocedural use of octreotide was not associated with attenuation of intraprocedural hypotension.

Perioperative Outcomes for Radical Nephrectomy and Level III-IV Inferior Vena Cava Tumor Thrombectomy in Patients with Renal Cell Carcinoma.

OBJECTIVES: This study examined the characteristics, intraoperative, and postoperative course of patients undergoing inferior vena cava tumor thrombectomy for metastatic renal cell carcinoma. DESIGN: A single-center case series that reported demographic data and intraoperative and postoperative outcomes for patients with renal cell carcinoma undergoing inferior vena cava thrombectomy. SETTING: This investigation was performed at a large quaternary referral center. PARTICIPANTS: Adult patients (age ≥18) admitted to the authors' hospital from January 1, 2005, to March 10, 2017, undergoing inferior vena cava thrombectomy for level III and IV renal cell carcinoma. INTERVENTIONS: No interventions were performed. MEASUREMENTS AND MAIN RESULTS: Sixty-five patients who met the inclusion criteria were identified, with 31 patients diagnosed with level III and 34 with level IV renal cell carcinoma. Patients with level IV tumors were significantly more likely to have greater intraoperative blood loss, had longer surgical duration and hospital stays, and had more frequently required blood products, pressors, and cardiopulmonary bypass intraoperatively. Intraoperative transesophageal echo was more frequently used in level IV thrombectomy compared to level III (91.2% v 67.7%). Of patients with level IV thrombus, 41.2% developed postoperative atrial fibrillation compared to only 3.2% with level III thrombus. The 30-day mortality was 4.6% for both groups. CONCLUSIONS: Patients undergoing inferior vena cava tumor thrombectomy for renal cell carcinoma had more complex intraoperative and postoperative courses with level IV compared to level III tumor thrombus.

Development and external validation of a prognostic model for ischaemic stroke after surgery.

BACKGROUND: There is an under-recognised patient cohort at elevated risk of postoperative ischaemic stroke. We aimed to develop and validate a prognostic model for the identification of such patients at high risk of ischaemic stroke within 1 yr after noncardiac surgery. METHODS: This was a hospital registry study of adult patients undergoing noncardiac surgery between 2005 and 2017 at two independent healthcare networks in Massachusetts, USA without a preoperative indication for therapeutic anticoagulation. Logistic regression was used to fit a model from a priori defined candidate predictors for the outcome 1 yr postoperative ischaemic stroke. To enhance clinical applicability, the model was simplified to a scoring system and externally validated. RESULTS: In the development (n=107 756) and validation (n=141 724) cohorts, 1.4% and 0.5% of patients had an ischaemic stroke up to 1 yr postoperatively. The final model included 13 variables (patient characteristics, comorbidities, procedural factors), considering sub-models conditional on a previous history of ischaemic stroke. Areas under the curve were 0.89 (95% confidence interval 0.89-0.90) and 0.88 (95% confidence interval 0.86-0.89) in the development and validation cohorts. Decision curve analysis indicated positive net benefits superior to other prediction instruments. CONCLUSIONS: Stroke after surgery (STRAS) screening can reliably identify patients with a high risk for ischaemic stroke during the first year after surgery. A STRAS-guided risk stratification may inform the recruitment to future randomised trials testing the efficacy of treatments for the prevention of postoperative ischaemic stroke.

Iron Oxide Nanoparticle Delivery of Peptides to the Brain: Reversal of Anxiety during Drug Withdrawal.

Targeting neuropeptide systems is important for future advancements in treatment of neurological and psychiatric illnesses. However, many of the peptides and their analogs do not cross the blood-brain barrier (BBB) efficiently. Nanoparticles such as iron oxide can cross the BBB, and here we describe a novel method for the conjugation of a peptide antisauvagine-30 (ASV-30) to iron oxide nanoparticles. Previous research has shown that direct infusion of ASV-30 into the brain reduces anxiety-like behavior in animal models via actions on corticotropin releasing factor type 2 (CRF2) receptors. Therefore, we tested whether iron oxide+ASV-30 complexes cross the BBB of rats and then determined whether iron oxide+ASV-30 nanoparticles are localized with CRF2-expressing neurons. Finally we tested the hypothesis that systemic infusion of iron oxide+ASV-30 can reduce anxiety-like behavior. First we describe the synthesis and demonstrate the stability of iron oxide-peptide nanoparticle complexes. Next, nanoparticles (87.7 µg/kg Fe2O3) with or without ASV-30 (200 µg/kg, ip) were injected into male rats 30 min prior to transcardial perfusion and brain fixation for immunohistochemical analysis, or before testing on the elevated plus maze (EPM) in an amphetamine withdrawal model of anxiety. Systemically administered iron oxide+ASV-30 particles were present in the brain and associated with neurons, including those that express CRF2 receptors, but did not localize with the iron storage protein ferritin. Furthermore, systemic administration of ironoxide+ASV-30 reduced amphetamine withdrawal-induced anxiety without affecting locomotion, suggesting that the anxiolytic effects of ASV-30 were preserved and the bioavailability of ASV-30 was sufficient. The findings demonstrate a novel approach to peptide delivery across the BBB and provide insight as to the neural distribution and efficacy of this nanotechnology.