Association Between Smoking and Postoperative Delirium in Surgical Patients With Pulmonary Hypertension: a Secondary Analysis of a Cohort Study

Background: Previous studies have declared that smoking is a risk factor for postoperative delirium (POD), but others have inconsistent results. Up till now, the association between smoking and POD has not been verified. This study aims to investigate the relationship between smoking and POD in patients with pulmonary hypertension (PHTN) in the United States.Methods: This study is a secondary analysis of a retrospective cohort study completed by Aalap C. et al. Patients with PHTN who underwent non-cardiac, non-obstetric surgery were enrolled in the original study. We further excluded the patients undergoing intracranial surgery and the patients with sepsis and perioperative stroke to avoid interference with POD assessment. The generalized linear model and generalized additive model were used to explore the relationship between smoking and POD.Results: After adjusting the potential confounders (age, gender, BMI, poor functional status, PHTN severity, some comorbidities such as hypertension, angina, coronary artery disease, arrhythmia, COPD, asthma, diabetes and renal failure, length of surgery, open surgical approach, intraabdominal surgery, intrathoracic surgery, vascular surgery, some medications such as anticoagulant, antiplatelet, steroids, statin, and atropine, some inhalational anesthesia agent such as isoflurane and sevoflurane), a positive relationship was found between smoking status and POD (OR=5.61, 95% CI: 1.14 to 27.51, P=0.0334). In addition, the curvilinear relationship between smoking burden (pack-years) and POD is close to a linear relationship.Conclusion: Smoking shows a positive correlation with POD in patients with PHTN. Surgical individuals need to prevent POD especially those with a heavy smoking burden.

Intraoperative Ultrasound Applications in Intracranial Surgery

The methods and use of intraoperative ultrasound in 33 canine and five feline patients and its ability to localize and identify anatomical structures and pathological lesions in canines and felines undergoing intracranial surgery are described from a case series. All were client-owned referral patients admitted for neurologic evaluation, with an advanced imaging diagnosis of an intracranial lesion, and underwent surgical biopsy or surgical removal of the lesion. Medical records, retrieval and review of imaging reports, and characterization of findings for all canine and feline patients show that intraoperative ultrasound guidance was used in intracranial procedures during the period of 2012 and 2019. Twenty-nine of the canine patients had intracranial tumors. The remainder had various other conditions requiring intracranial intervention. Three of the feline patients had meningiomas, one had a depressed skull fracture, and one had an epidural hematoma. The tumors appeared hyperechoic on intraoperative ultrasound with the exception of cystic portions of the masses and correlated with the size and location seen on advanced imaging. Statistical comparison of the size of images seen on ultrasound and on MRI for 20 of the canine tumors revealed no statistical differences. Neuroanatomical structures, including vascular components, were easily identified, and tumor images correlated well with preoperative advanced imaging. The authors conclude that intraoperative ultrasound is a valuable asset in intracranial mass removals and can augment surgical guidance in a variety of intracranial disorders that require surgery. This is the first known publication in veterinary surgery of using intraoperative ultrasound as a tool in the operating theater to identify, localize, and monitor the removal/biopsy of intracranial lesions in small animals undergoing craniotomy/craniectomy.

Severity assessment of complex and repeated intracranial surgery in rats

Introduction Evidence-based grading of the impact of intracranial surgery on rat’s well-being is important for ethical and legal reasons. We assessed the severity of complex and repeated intracranial surgery in a 6-hydroxydopamine (6-OHDA) Parkinson’s rat model with subsequent intracranial electrode implantation, and in an intracranial tumor model with subsequent resection. Methods Stereotactic surgery was performed in adult male rats with the same general anesthesia and perioperative pain management. In the Parkinson’s model, Sprague Dawley (SD) rats received unilateral injection of 6-OHDA (n=11) or vehicle (n=7) into the medial forebrain bundle as first operation. After four weeks, neural electrodes were implanted in all rats as second operation. For tumor formation, BDIX/ UlmHanZtm (BDIX) rats (n=8) received frontocortical injection of BT4Ca cells as first operation, followed by tumor resection as second operation after one week. Multiple measures severity assessment was done two days before and four days after surgery in all rats, comprising clinical scoring, body weight and detailed behavioral screening. To include a condition with a known burden, rats with intracranial tumors were additionally assessed up to a predefined humane endpoint that has previously been classified as "moderate". Results After the first operation, only 6-OHDA injection resulted in transient elevated clinical scores, a mild long-lasting weight reduction and motor disturbances. After the second surgery, body weight was transiently reduced in all groups. All other parameters showed variable results. Principal Component Analysis showed a separation from the preoperative state driven by motor-related parameters after 6-OHDA injection, while separation after electrode implantation and more clearly after tumor resection was driven by pain-related parameters, although not reaching the level of the humane endpoint of our tumor model. Conclusion Overall, cranial surgery of different complexity only transiently and rather mildly affects rat’s well-being. Multiple measures assessment allows the differentiation of model-related motor disturbances in the Parkinson’s model from potentially pain-related conditions after tumor resection and electrode implantation.

Delirium in neurosurgery: a systematic review and meta-analysis

Delirium is a frequent occurring complication in surgical patients. Nevertheless, a scientific work-up of the clinical relevance of delirium after intracranial surgery is lacking. We conducted a systematic review (CRD42020166656) to evaluate the current diagnostic work-up, incidence, risk factors and health outcomes of delirium in this population. Five databases (Embase, Medline, Web of Science, PsycINFO, Cochrane Central) were searched from inception through March 31st, 2021. Twenty-four studies (5589 patients) were included for qualitative analysis and twenty-one studies for quantitative analysis (5083 patients). Validated delirium screening tools were used in 70% of the studies, consisting of the Confusion Assessment Method (intensive care unit) (45%), Delirium Observation Screening Scale (5%), Intensive Care Delirium Screening Checklist (10%), Neelon and Champagne Confusion Scale (5%) and Nursing Delirium Screening Scale (5%). Incidence of post-operative delirium after intracranial surgery was 19%, ranging from 12 to 26% caused by variation in clinical features and delirium assessment methods. Meta-regression for age and gender did not show a correlation with delirium. We present an overview of risk factors and health outcomes associated with the onset of delirium. Our review highlights the need of future research on delirium in neurosurgery, which should focus on optimizing diagnosis and assessing prognostic significance and management.

Neurotrophic Factors in Parkinson’s Disease: Clinical Trials, Open Challenges and Nanoparticle-Mediated Delivery to the Brain

Neurotrophic factors (NTFs) are small secreted proteins that support the development, maturation and survival of neurons. NTFs injected into the brain rescue and regenerate certain neuronal populations lost in neurodegenerative diseases, demonstrating the potential of NTFs to cure the diseases rather than simply alleviating the symptoms. NTFs (as the vast majority of molecules) do not pass through the blood–brain barrier (BBB) and therefore, are delivered directly into the brain of patients using costly and risky intracranial surgery. The delivery efficacy and poor diffusion of some NTFs inside the brain are considered the major problems behind their modest effects in clinical trials. Thus, there is a great need for NTFs to be delivered systemically thereby avoiding intracranial surgery. Nanoparticles (NPs), particles with the size dimensions of 1-100 nm, can be used to stabilize NTFs and facilitate their transport through the BBB. Several studies have shown that NTFs can be loaded into or attached onto NPs, administered systemically and transported to the brain. To improve the NP-mediated NTF delivery through the BBB, the surface of NPs can be functionalized with specific ligands such as transferrin, insulin, lactoferrin, apolipoproteins, antibodies or short peptides that will be recognized and internalized by the respective receptors on brain endothelial cells. In this review, we elaborate on the most suitable NTF delivery methods and envision “ideal” NTF for Parkinson’s disease (PD) and clinical trial thereof. We shortly summarize clinical trials of four NTFs, glial cell line-derived neurotrophic factor (GDNF), neurturin (NRTN), platelet-derived growth factor (PDGF-BB), and cerebral dopamine neurotrophic factor (CDNF), that were tested in PD patients, focusing mainly on GDNF and CDNF. We summarize current possibilities of NP-mediated delivery of NTFs to the brain and discuss whether NPs have impact in improving the properties of NTFs and delivery across the BBB. Emerging delivery approaches and future directions of NTF-based nanomedicine are also discussed.

Reducing Superfluous Opioid Prescribing Practices After Brain Surgery: It Is Time to Talk About Drugs

BACKGROUND Opioids are prescribed routinely after cranial surgery despite a paucity of evidence regarding the optimal quantity needed. Overprescribing may adversely contribute to opioid abuse, chronic use, and diversion. OBJECTIVE To evaluate the effectiveness of a system-wide campaign to reduce opioid prescribing excess while maintaining adequate analgesia. METHODS A retrospective cohort study of patients undergoing a craniotomy for tumor resection with home disposition before and after a 2-mo educational intervention was completed. The educational initiative was composed of directed didactic seminars targeting senior staff, residents, and advanced practice providers. Opioid prescribing patterns were then assessed for patients discharged before and after the intervention period. RESULTS A total of 203 patients were discharged home following a craniotomy for tumor resection during the study period: 98 who underwent surgery prior to the educational interventions compared to 105 patients treated post-intervention. Following a 2-mo educational period, the quantity of opioids prescribed decreased by 52% (median morphine milligram equivalent per day [interquartile range], 32.1 [16.1, 64.3] vs 15.4 [0, 32.9], P < .001). Refill requests also decreased by 56% (17% vs 8%, P = .027) despite both groups having similar baseline characteristics. There was no increase in pain scores at outpatient follow-up (1.23 vs 0.85, P = .105). CONCLUSION A dramatic reduction in opioids prescribed was achieved without affecting refill requests, patient satisfaction, or perceived analgesia. The use of targeted didactic education to safely improve opioid prescribing following intracranial surgery uniquely highlights the ability of simple, evidence-based interventions to impact clinical decision making, lessen potential patient harm, and address national public health concerns.

Charcot's motor brain map and 19th-century neurosurgery

Neurosurgery is predicated on the knowledge of the structure-function relationship of the brain. When the topic is broached in its historiography, it begins with Fritch and Hitzig's report on the localization of motor function in the cortex of the dog and skips rapidly to Wilder Penfield's homunculus. In that gap are found the origins of modern neurosurgery in 3 papers published by Jean-Martin Charcot and Albert Pitres between 1877 and 1879 in which they describe the somatotopic organization of the human motor cortex and draw the first human brain map. Their findings, obtained through the clinicopathological method, gave relevance to David Ferrier's observations in animals. Their work was extensively cited, and their illustrations reproduced by Ferrier in his landmark lecture to the Royal College of Physicians in 1878. It was known to William Macewen, who used localization to guide him in resecting intracranial mass lesions, and to William Osler and John Hughlings Jackson, who were early advocates of intracranial surgery. This paper describes Charcot and Pitres' discovery of the cortical origin of human voluntary movement and its somatotopic organization, and their influence on 19th-century intracranial surgery. It fills a gap in the historiography of cerebral localization and neurosurgery.

Idiopathic superficial siderosis of the central nervous system

Background Regardless of the cause of the superficial siderosis (SS) disease, which is bleeding, the source of bleeding cannot be found in some cases. Case presentation In this article, we report two cases with idiopathic SS. Case 1 presented with bilateral hearing loss, cognitive impairment, sleep disturbances, and tremors. Case 2 presented with sensory neural hearing loss, ataxia, and spastic paraparesis. In both cases, brain MRI indicated evidence of SS. CT myelogram and SPECT with labeled RBC couldn’t help finding the source of occult bleeding. Conclusion SS is a rare central nervous system disease caused by the deposition of hemosiderin in the brain and spinal cord, which results in the progression of neurological deficits. The cause of this hemorrhage is often subarachnoid haemorrhage, intracranial surgery, carcinoma, arteriovenous malformation, nerve root avulsion, and dural abnormality. The condition progresses slowly and, by the time diagnosis is confirmed, the damage is often irreversible. In our cases, brain MRI clarified the definitive diagnosis, but we could not find the source of bleeding. SS should be considered in cases with ataxia and hearing loss, even if no source of bleeding is found.

Development of an Early Prediction Model for Postoperative Delirium in Neurosurgical Patients Admitted to the ICU after Elective Craniotomy (E-PREPOD-NS): A Secondary Analysis of A Prospective Cohort Study

Background: Postoperative delirium (POD) is a significant clinical problem in neurosurgical patients after intracranial surgery. Identification of high-risk patients may optimise individual perioperative management, but an adequate and simple risk model for use at super early phase after operation has not been developed.Methods: Adult patients were admitted to the ICU after elective intracranial surgery under general anaesthesia. The POD was diagnosed as Confusion Assessment Method for the ICU positive on postoperative day 1 to 3. Multivariate logistic regression analysis was used to develop the early prediction model (E-PREPOD-NS) and the final model was validated with 200 bootstrap samples.Results: Among 800 patients included in the study, POD occurred in 157 cases (19.6%). We identified nine variables independently associated with POD in the final E-PREPOD-NS model: age > 65 years [odds ratio (OR) = 3.336, 95% confidence interval (CI) = 1.765-6.305, 1 risk score point], education level < 9 years (OR = 2.528, 95% CI = 1.446-4.419, 1 point), history of smoking (OR = 2.582, 95% CI = 1.611-4.140, 1 point), history of diabetes (OR = 2.541, 95% CI = 1.201-5.377, 1 point), supra-tentorial lesions (OR = 3.424, 95% CI = 2.021-5.802, 1 point), anesthesia duration > 360 min (OR = 1.686, 95% CI = 1.062-2.674, 0.5 point), GCS <9 at ICU admission (OR = 6.059, 95% CI = 3.789-9.690, 1.5 points), metabolic acidosis (OR = 13.903, 95% CI = 6.248-30.938, 2.5 points), and positioning of neurosurgical drainage tube (OR = 1.924, 95% CI = 1.132-3.269, 0.5 point). The area under the receiver operator curve (AUROC) of the risk score for prediction of POD was 0.865 (95% CI = 0.835-0.895). After internal validation by bootstrap, the AUROC was 0.851 (95% CI = 0.791-0.912). The model showed good calibration (Hosmer-Lemeshow P = 0.593).Conclusions: The E-PREPOD-NS model based on nine perioperative risk factors can predict POD in patients admitted to the ICU after elective intracranial surgery with fairly good accuracy. External validation is needed before use in clinical practice.