Propofol-Based Anesthesia Maintenance and/or Volatile Anesthetics during Intracranial Aneurysm Repair: A Comparative Analysis of Neurological Outcomes.

BACKGROUND: Volatile and intravenous anesthetics have substantial effects on physiological functions, notably influencing neurological function and susceptibility to injury. Despite the importance of the anesthetic approach, data on its relative risks or benefits during surgical clipping or endovascular treatments for unruptured intracranial aneurysms (UIAs) remains scant. We investigated whether using volatile anesthetics alone or in combination with propofol infusion yields superior neurological outcomes following UIA obliteration. METHODS: We retrospectively reviewed 1001 patients who underwent open or endovascular treatment for UIA, of whom 596 had short- and long-term neurological outcome data (modified Rankin Scale) recorded. Multivariable ordinal regression analysis was performed to examine the association between the anesthetic approach and outcomes. RESULTS: Of 1001 patients, 765 received volatile anesthetics alone, while 236 received propofol infusion and volatile anesthetics (combined anesthetic group). Short-term neurological outcome data were available for 619 patients and long-term data for 596. No significant correlation was found between the anesthetic approach and neurologic outcomes, irrespective of the type of procedure (open craniotomy or endovascular treatment). The combined anesthetic group had a higher rate of ICU admission (p < 0.001) and longer ICU and hospital length of stay (LOS, p < 0.001). Similarly, a subgroup analysis revealed longer ICU and hospital LOS (p < 0.0001 and p < 0.001, respectively) in patients who underwent endovascular UIA obliteration under a combined anesthetic approach (n = 678). CONCLUSIONS: The addition of propofol to volatile anesthetics during UIA obliteration does not provide short- or long-term benefits to neurologic outcomes. Compared to volatile anesthetics alone, the combination of propofol and volatile anesthetics may be associated with an increased rate of ICU admission, as well as longer ICU and hospital LOS.

High Incidence of Postoperative Nausea and Vomiting in Transgender Women Undergoing Facial Feminization Procedures.

Background: Postoperative nausea and vomiting (PONV) is a significant concern due to its impact on patient comfort, recovery time, and extended hospital stay. Previous research links higher PONV rates in women during their periovulatory phase to estrogen. This study investigates the PONV risk in transgender women after facial feminization surgery. Methods: Retrospective chart reviews of transgender women aged older than 18 undergoing facial feminization from 2014 to 2020 were undertaken. Data included demographics, hormone use history, comorbidities, and PONV history. PONV was classified as any nausea/vomiting episode before discharge. Anesthesia records were examined, and PACU notes were analyzed for PONV indicators. A cis-gender male and female cohort undergoing rhinoplasty served as controls. Results: Of the 282 transgender women receiving facial feminization surgery, 104 experienced PONV, marking a 37% PONV rate. Compared with the 11% PONV rate among cis-gender rhinoplasty patients, this was notably higher. Hormone therapy discontinuation showed no influence on PONV incidence. Conclusions: Transgender women undergoing facial feminization surgery have a 38% PONV rate, surpassing the 11% rate in cis-gender rhinoplasty patients and the general 20%-30% rate for all procedures, including the 25% for oral and maxillofacial surgery. This suggests a heightened PONV risk for transgender women after facial feminization procedures.

Nanowired delivery of antibodies to tau and neuronal nitric oxide synthase together with cerebrolysin attenuates traumatic brain injury induced exacerbation of brain pathology in Parkinson's disease.

Concussive head injury (CHI) is one of the major risk factors for developing Parkinson's disease in later life of military personnel affecting lifetime functional and cognitive disturbances. Till date no suitable therapies are available to attenuate CHI or PD induced brain pathology. Thus, further exploration of novel therapeutic agents are highly warranted using nanomedicine in enhancing the quality of life of veterans or service members of US military. Since PD or CHI induces oxidative stress and perturbs neurotrophic factors regulation associated with phosphorylated tau (p-tau) deposition, a possibility exists that nanodelivery of agents that could enhance neurotrophic factors balance and attenuate oxidative stress could be neuroprotective in nature. In this review, nanowired delivery of cerebrolysin-a balanced composition of several neurotrophic factors and active peptide fragments together with monoclonal antibodies to neuronal nitric oxide synthase (nNOS) with p-tau antibodies was examined in PD following CHI in model experiments. Our results suggest that combined administration of nanowired antibodies to nNOS and p-tau together with cerebrolysin significantly attenuated CHI induced exacerbation of PD brain pathology. This combined treatment also has beneficial effects in CHI or PD alone, not reported earlier.

Co-administration of dl-3-n-butylphthalide and neprilysin is neuroprotective in Alzheimer disease associated with mild traumatic brain injury.

dl-3-n-Butylphthalide is a potent synthetic Chinese celery extract that is highly efficient in inducing neuroprotection in concussive head injury (CHI), Parkinson's disease, Alzheimer's disease, stroke as well as depression, dementia, anxiety and other neurological diseases. Thus, there are reasons to believe that dl-3-n-butylphthalide could effectively prevent Alzheimer's disease brain pathology. Military personnel during combat operation or veterans are often the victims of brain injury that is a major risk factor for developing Alzheimer's disease in their later lives. In our laboratory we have shown that CHI exacerbates Alzheimer's disease brain pathology and reduces the amyloid beta peptide (AßP) inactivating enzyme neprilysin. We have used TiO2 nanowired-dl-3-n-butylphthalide in attenuating Parkinson's disease brain pathology exacerbated by CHI. Nanodelivery of dl-3-n-butylphthalide appears to be more potent as compared to the conventional delivery of the compound. Thus, it would be interesting to examine the effects of nanowired dl-3-n-butylphthalide together with nanowired delivery of neprilysin in Alzheimer's disease model on brain pathology. In this investigation we found that nanowired delivery of dl-3-n-butylphthalide together with nanowired neprilysin significantly attenuated brain pathology in Alzheimer's disease model with CHI, not reported earlier. The possible mechanism and clinical significance is discussed based on the current literature.

Nicotine neurotoxicity exacerbation following engineered Ag and Cu (50-60 nm) nanoparticles intoxication. Neuroprotection with nanowired delivery of antioxidant compound H-290/51 together with serotonin 5-HT3 receptor antagonist ondansetron.

Nicotine abuse is frequent worldwide leading to about 8 millions people die every year due to tobacco related diseases. Military personnel often use nicotine smoking that is about 12.8% higher than civilian populations. Nicotine smoking triggers oxidative stress and are linked to several neurodegenerative diseases such as Alzheimer's disease. Nicotine neurotoxicity induces significant depression and oxidative stress in the brain leading to neurovascular damages and brain pathology. Thus, details of nicotine neurotoxicity and factors influencing them require additional investigations. In this review, effects of engineered nanoparticles from metals Ag and Cu (50-60 nm) on nicotine neurotoxicity are discussed with regard to nicotine smoking. Military personnel often work in the environment where chances of nanoparticles exposure are quite common. In our earlier studies, we have shown that nanoparticles alone induces breakdown of the blood-brain barrier (BBB) and exacerbates brain pathology in animal models. In present investigation, nicotine exposure in with Ag or Cu nanoparticles intoxicated group exacerbated BBB breakdown, induce oxidative stress and aggravate brain pathology. Treatment with nanowired H-290/51 a potent chain-breaking antioxidant together with nanowired ondansetron, a potent 5-HT3 receptor antagonist significantly reduced oxidative stress, BBB breakdown and brain pathology in nicotine exposure associated with Ag or Cu nanoparticles intoxication. The functional significance of this findings and possible mechanisms of nicotine neurotoxicity are discussed based on current literature.

Spinal cord injury induced exacerbation of Alzheimer's disease like pathophysiology is reduced by topical application of nanowired cerebrolysin with monoclonal antibodies to amyloid beta peptide, p-tau and tumor necrosis factor alpha.

Hallmark of Alzheimer's disease include amyloid beta peptide and phosphorylated tau deposition in brain that could be aggravated following traumatic of concussive head injury. However, amyloid beta peptide or p-tau in spinal cord following injury is not well known. In this investigation we measured amyloid beta peptide and p-tau together with tumor necrosis factor-alpha (TNF-α) in spinal cord and brain following 48 h after spinal cord injury in relation to the blood-spinal cord and blood-brain barrier, edema formation, blood flow changes and cell injury in perifocal regions of the spinal cord and brain areas. A focal spinal cord injury was inflicted over the right dorsal horn of the T10-11 segment (4 mm long and 2 mm deep) and amyloid beta peptide and p-tau was measured in perifocal rostral (T9) and caudal (T12) spinal cord segments as well as in the brain areas. Our observations showed a significant increase in amyloid beta peptide in the T9 and T12 segments as well as in remote areas of brain and spinal cord after 24 and 48 h injury. This is associated with breakdown of the blood-spinal cord (BSCB) and brain barriers (BBB), edema formation, reduction in blood flow and cell injury. After 48 h of spinal cord injury elevation of amyloid beta peptide, phosphorylated tau (p-tau) and tumor necrosis factor-alpha (TNF-α) was seen in T9 and T12 segments of spinal cord in cerebral cortex, hippocampus and brain stem regions associated with microglial activation as seen by upregulation of Iba1 and CD86. Repeated nanowired delivery of cerebrolysin topically over the traumatized segment repeatedly together with monoclonal antibodies (mAb) to amyloid beta peptide (AßP), p-tau and TNF-α significantly attenuated amyloid beta peptide, p-tau deposition and reduces Iba1, CD68 and TNF-α levels in the brain and spinal cord along with blockade of BBB and BSCB, reduction in blood flow, edema formation and cell injury. These observations are the first to show that spinal cord injury induces Alzheimer's disease like symptoms in the CNS, not reported earlier.

No Thromboembolic Complications After Facial Feminization Surgery in Transgender Patients Utilizing Estrogen Therapy: A Retrospective Cohort Study.

Purpose: Estrogen therapy is associated with an increased risk of venous thromboembolism (VTE). A large proportion of transfeminine patients use estrogen therapy before undergoing gender-affirming surgery. Many surgeons implement the discontinuation of hormone therapy before surgery. This study sought to evaluate the perioperative risk of VTE in transfeminine patients undergoing the procedure of facial feminization. Methods: Retrospective chart reviews were performed of all patients who underwent facial feminization by a single surgeon at an urban academic institution from 2014 to 2020. Patient characteristics including comorbidities, Caprini score, VTE chemoprophylaxis, and perioperative hormone therapy management were reviewed. The incidences of VTE during perioperative hospital stay and within 1 week and 6 months after the surgical procedure were examined. Results: There were 296 facial feminization procedures performed on 282 distinct patients who met criteria for inclusion in the study. Hormone therapy was prescribed to 83.6% of patients, 69.5% of whom reported that they held these medications before the procedure. Of those holding, 84.1% of patients reported they discontinued these medications between 2 and 4 weeks. No patients received VTE chemoprophylaxis. There were 0 VTE incidents during the patients' perioperative period up to 6 months postprocedure. Conclusion: Our findings support that transfeminine patients who use estrogen hormone therapy are at a minimal risk to experience VTE when undergoing facial feminization procedures. Future directions include evaluating the psychologic effect of discontinuing hormone therapy to help guide perioperative decision making.

Nanowired Delivery of Cerebrolysin Together with Antibodies to Amyloid Beta Peptide, Phosphorylated Tau, and Tumor Necrosis Factor Alpha Induces Superior Neuroprotection in Alzheimer's Disease Brain Pathology Exacerbated by Sleep Deprivation.

Sleep deprivation induces amyloid beta peptide and phosphorylated tau deposits in the brain and cerebrospinal fluid together with altered serotonin metabolism. Thus, it is likely that sleep deprivation is one of the predisposing factors in precipitating Alzheimer's disease (AD) brain pathology. Our previous studies indicate significant brain pathology following sleep deprivation or AD. Keeping these views in consideration in this review, nanodelivery of monoclonal antibodies to amyloid beta peptide (AßP), phosphorylated tau (p-tau), and tumor necrosis factor alpha (TNF-α) in sleep deprivation-induced AD is discussed based on our own investigations. Our results suggest that nanowired delivery of monoclonal antibodies to AßP with p-tau and TNF-α induces superior neuroprotection in AD caused by sleep deprivation, not reported earlier.

Co-administration of Nanowired DL-3-n-Butylphthalide (DL-NBP) Together with Mesenchymal Stem Cells, Monoclonal Antibodies to Alpha Synuclein and TDP-43 (TAR DNA-Binding Protein 43) Enhance Superior Neuroprotection in Parkinson's Disease Following Concussive Head Injury.

dl-3-n-butylphthalide (dl-NBP) is one of the potent antioxidant compounds that induces profound neuroprotection in stroke and traumatic brain injury. Our previous studies show that dl-NBP reduces brain pathology in Parkinson's disease (PD) following its nanowired delivery together with mesenchymal stem cells (MSCs) exacerbated by concussive head injury (CHI). CHI alone elevates alpha synuclein (ASNC) in brain or cerebrospinal fluid (CSF) associated with elevated TAR DNA-binding protein 43 (TDP-43). TDP-43 protein is also responsible for the pathologies of PD. Thus, it is likely that exacerbation of brain pathology in PD following brain injury may be thwarted using nanowired delivery of monoclonal antibodies (mAb) to ASNC and/or TDP-43. In this review, the co-administration of dl-NBP with MSCs and mAb to ASNC and/or TDP-43 using nanowired delivery in PD and CHI-induced brain pathology is discussed based on our own investigations. Our observations show that co-administration of TiO2 nanowired dl-NBP with MSCs and mAb to ASNC with TDP-43 induced superior neuroprotection in CHI induced exacerbation of brain pathology in PD, not reported earlier.

Co-Administration of Nanowired Monoclonal Antibodies to Inducible Nitric Oxide Synthase and Tumor Necrosis Factor Alpha Together with Antioxidant H-290/51 Reduces SiO2 Nanoparticles-Induced Exacerbation of Pathophysiology of Spinal Cord Trauma.

Military personnel are often exposed to silica dust during combat operations across the globe. Exposure to silica dust in US military or service personnel could cause Desert Strom Pneumonitis also referred to as Al Eskan disease causing several organs damage and precipitate autoimmune dysfunction. However, the effects of microfine particles of sand inhalation-induced brain damage on the pathophysiology of traumatic brain or spinal cord injury are not explored. Previously intoxication of silica nanoparticles (50-60 nm size) is shown to exacerbates spinal cord injury induces blood-spinal cord barrier breakdown, edema formation and cellular changes. However, the mechanism of silica nanoparticles-induced cord pathology is still not well known. Spinal cord injury is well known to alter serotonin (5-hydroxytryptamine) metabolism and induce oxidative stress including upregulation of nitric oxide synthase and tumor necrosis factor alpha. This suggests that these agents are involved in the pathophysiology of spinal cord injury. In this review, we examined the effects of combined nanowired delivery of monoclonal antibodies to neuronal nitric oxide synthase (nNOS) together with tumor necrosis factor alpha (TNF-α) antibodies and a potent antioxidant H-290/51 to induce neuroprotection in spinal cord injury associated with silica nanoparticles intoxication. Our results for the first time show that co-administration of nanowired delivery of antibodies to nNOS and TNF-α with H-290/51 significantly attenuated silica nanoparticles-induced exacerbation of spinal cord pathology, not reported earlier.

Neuroprotective Effects of Nanowired Delivery of Cerebrolysin with Mesenchymal Stem Cells and Monoclonal Antibodies to Neuronal Nitric Oxide Synthase in Brain Pathology Following Alzheimer's Disease Exacerbated by Concussive Head Injury.

Concussive head injury (CHI) is one of the major risk factors in developing Alzheimer's disease (AD) in military personnel at later stages of life. Breakdown of the blood-brain barrier (BBB) in CHI leads to extravasation of plasma amyloid beta protein (ΑßP) into the brain fluid compartments precipitating AD brain pathology. Oxidative stress in CHI or AD is likely to enhance production of nitric oxide indicating a role of its synthesizing enzyme neuronal nitric oxide synthase (NOS) in brain pathology. Thus, exploration of the novel roles of nanomedicine in AD or CHI reducing NOS upregulation for neuroprotection are emerging. Recent research shows that stem cells and neurotrophic factors play key roles in CHI-induced aggravation of AD brain pathologies. Previous studies in our laboratory demonstrated that CHI exacerbates AD brain pathology in model experiments. Accordingly, it is quite likely that nanodelivery of NOS antibodies together with cerebrolysin and mesenchymal stem cells (MSCs) will induce superior neuroprotection in AD associated with CHI. In this review, co-administration of TiO2 nanowired cerebrolysin - a balanced composition of several neurotrophic factors and active peptide fragments, together with MSCs and monoclonal antibodies (mAb) to neuronal NOS is investigated for superior neuroprotection following exacerbation of brain pathology in AD exacerbated by CHI based on our own investigations. Our observations show that nanowired delivery of cerebrolysin, MSCs and neuronal NOS in combination induces superior neuroprotective in brain pathology in AD exacerbated by CHI, not reported earlier.

Nanowired Delivery of Cerebrolysin with Mesenchymal Stem Cells Attenuates Heat Stress-Induced Exacerbation of Neuropathology Following Brain Blast Injury.

Blast brain injury (bBI) following explosive detonations in warfare is one of the prominent causes of multidimensional insults to the central nervous and other vital organs injury. Several military personnel suffered from bBI during the Middle East conflict at hot environment. The bBI largely occurs due to pressure waves, generation of heat together with release of shrapnel and gun powders explosion with penetrating and/or impact head trauma causing multiple brain damage. As a result, bBI-induced secondary injury causes breakdown of the blood-brain barrier (BBB) and edema formation that further results in neuronal, glial and axonal injuries. Previously, we reported endocrine imbalance and influence of diabetes on bBI-induced brain pathology that was significantly attenuated by nanowired delivery of cerebrolysin in model experiments. Cerebrolysin is a balanced composition of several neurotrophic factors, and active peptide fragment is capable of neuroprotection in several neurological insults. Exposure to heat stress alone causes BBB damage, edema formation and brain pathology. Thus, it is quite likely that hot environment further exacerbates the consequences of bBI. Thus, novel therapeutic strategies using nanodelivery of stem cell and cerebrolysin may further enhance superior neuroprotection in bBI at hot environment. Our observations are the first to show that combined nanowired delivery of mesenchymal stem cells (MSCs) and cerebrolysin significantly attenuated exacerbation of bBI in hot environment and induced superior neuroprotection, not reported earlier. The possible mechanisms of neuroprotection with MSCs and cerebrolysin in bBI are discussed in the light of current literature.

Co-administration of Nanowired Oxiracetam and Neprilysin with Monoclonal Antibodies to Amyloid Beta Peptide and p-Tau Thwarted Exacerbation of Brain Pathology in Concussive Head Injury at Hot Environment.

Environmental temperature adversely affects the outcome of concussive head injury (CHI)-induced brain pathology. Studies from our laboratory showed that animals reared at either cold environment or at hot environment exacerbate brain pathology following CHI. Our previous experiments showed that nanowired delivery of oxiracetam significantly attenuated CHI-induced brain pathology and associated neurovascular changes. Military personnel are the most susceptible to CHI caused by explosion, blasts, missile or blunt head trauma leading to lifetime functional and cognitive impairments affecting the quality of life. Severe CHI leads to instant death and/or lifetime paralysis. Military personnel engaged in combat operations are often subjected to extreme high or low environmental temperature zones across the globe. Thus, further exploration of novel therapeutic agents at cold or hot ambient temperatures following CHI are the need of the hour. CHI is also a major risk factor for developing Alzheimer's disease by enhancing amyloid beta peptide deposits in the brain. In this review, effect of hot environment on CHI-induced brain pathology is discussed. In addition, whether nanodelivery of oxiracetam together with neprilysin and monoclonal antibodies (mAb) to amyloid beta peptide and p-tau could lead to superior neuroprotection in CHI is explored. Our results show that co-administration of oxiracetam with neprilysin and mAb to AßP and p-tau significantly induced superior neuroprotection following CHI in hot environment, not reported earlier.

Nanowired Delivery of Mesenchymal Stem Cells with Antioxidant Compound H-290/51 Reduces Exacerbation of Methamphetamine Neurotoxicity in Hot Environment.

Military personnel are often exposed to hot environments either for combat operations or peacekeeping missions. Hot environment is a severe stressful situation leading to profound hyperthermia, fatigue and neurological impairments. To avoid stressful environment, some people frequently use methamphetamine (METH) or other psychostimulants to feel comfortable under adverse situations. Our studies show that heat stress alone induces breakdown of the blood-brain barrier (BBB) and edema formation associated with reduced cerebral blood flow (CBF). On the other hand, METH alone induces hyperthermia and neurotoxicity. These effects of METH are exacerbated at high ambient temperatures as seen with greater breakdown of the BBB and brain pathology. Thus, a combination of METH use at hot environment may further enhance the brain damage-associated behavioral dysfunctions. METH is well known to induce severe oxidative stress leading to brain pathology. In this investigation, METH intoxication at hot environment was examined on brain pathology and to explore suitable strategies to induce neuroprotection. Accordingly, TiO2-nanowired delivery of H-290/51 (150 mg/kg, i.p.), a potent chain-breaking antioxidant in combination with mesenchymal stem cells (MSCs), is investigated in attenuating METH-induced brain damage at hot environment in model experiments. Our results show that nanodelivery of H-290/51 with MSCs significantly enhanced CBF and reduced BBB breakdown, edema formation and brain pathology following METH exposure at hot environment. These observations are the first to point out that METH exacerbated brain pathology at hot environment probably due to enhanced oxidative stress, and MSCs attenuate these adverse effects, not reported earlier.

Nanowired Delivery of Curcumin Attenuates Methamphetamine Neurotoxicity and Elevates Levels of Dopamine and Brain-Derived Neurotrophic Factor.

Curcumin is a well-known antioxidant used as traditional medicine in China and India since ages to treat variety of inflammatory ailments as a food supplement. Curcumin has antitumor properties with neuroprotective effects in Alzheimer's disease. Curcumin elevates brain-derived neurotrophic factor (BDNF) and dopamine (DA) levels in the brain indicating its role in substance abuse. Methamphetamine (METH) is one of the most abused substances in the world that induces profound neurotoxicity by inducing breakdown of the blood-brain barrier (BBB), vasogenic edema and cellular injuries. However, influence of curcumin on METH-induced neurotoxicity is still not well investigated. In this investigation, METH neurotoxicity and neuroprotective effects of curcumin nanodelivery were examined in a rat model. METH (20 mg/kg, i.p.) neurotoxicity is evident 4 h after its administration exhibiting breakdown of BBB to Evans blue albumin in the cerebral cortex, hippocampus, cerebellum, thalamus and hypothalamus associated with vasogenic brain edema as seen measured using water content in all these regions. Nissl attaining exhibited profound neuronal injuries in the regions of BBB damage. Normal curcumin (50 mg/kg, i.v.) 30 min after METH administration was able to reduce BBB breakdown and brain edema partially in some of the above brain regions. However, TiO2 nanowired delivery of curcumin (25 mg/kg, i.v.) significantly attenuated brain edema, neuronal injuries and the BBB leakage in all the brain areas. BDNF level showed a significant higher level in METH-treated rats as compared to saline-treated METH group. Significantly enhanced DA levels in METH-treated rats were also observed with nanowired delivery of curcumin. Normal curcumin was able to slightly elevate DA and BDNF levels in the selected brain regions. Taken together, our observations are the first to show that nanodelivery of curcumin induces superior neuroprotection in METH neurotoxicity probable by enhancing BDNF and DA levels in the brain, not reported earlier.

Cerebrolysin Attenuates Exacerbation of Neuropathic Pain, Blood-spinal Cord Barrier Breakdown and Cord Pathology Following Chronic Intoxication of Engineered Ag, Cu or Al (50-60 nm) Nanoparticles.

Neuropathic pain is associated with abnormal sensations and/or pain induced by non-painful stimuli, i.e., allodynia causing burning or cold sensation, pinching of pins and needles like feeling, numbness, aching or itching. However, no suitable therapy exists to treat these pain syndromes. Our laboratory explored novel potential therapeutic strategies using a suitable composition of neurotrophic factors and active peptide fragments-Cerebrolysin (Ever Neuro Pharma, Austria) in alleviating neuropathic pain induced spinal cord pathology in a rat model. Neuropathic pain was produced by constrictions of L-5 spinal sensory nerves for 2-10 weeks period. In one group of rats cerebrolysin (2.5 or 5 ml/kg, i.v.) was administered once daily after 2 weeks until sacrifice (4, 8 and 10 weeks). Ag, Cu and Al NPs (50 mg/kg, i.p.) were delivered once daily for 1 week. Pain assessment using mechanical (Von Frey) or thermal (Hot-Plate) nociceptive showed hyperalgesia from 2 weeks until 10 weeks progressively that was exacerbated following Ag, Cu and Al NPs intoxication in nerve lesioned groups. Leakage of Evans blue and radioiodine across the blood-spinal cord barrier (BSCB) is seen from 4 to 10 weeks in the rostral and caudal cord segments associated with edema formation and cell injury. Immunohistochemistry of albumin and GFAP exhibited a close parallelism with BSCB leakage that was aggravated by NPs following nerve lesion. Light microscopy using Nissl stain exhibited profound neuronal damages in the cord. Transmission electron microcopy (TEM) show myelin vesiculation and synaptic damages in the cord that were exacerbated following NPs intoxication. Using ELISA spinal tissue exhibited increased albumin, glial fibrillary acidic protein (GFAP), myelin basic protein (MBP) and heat shock protein (HSP 72kD) upregulation together with cytokines TNF-α, IL-4, IL-6, IL-10 levels in nerve lesion that was exacerbated following NPs intoxication. Cerebrolysin treatment significantly reduced hyperalgesia and attenuated BSCB disruption, edema formation and cellular changes in nerve lesioned group. The levels of cytokines were also restored near normal levels with cerebrolysin treatment. Albumin, GFAP, MABP and HSP were also reduced in cerebrolysin treated group and thwarted neuronal damages, myelin vesiculation and cell injuries. These neuroprotective effects of cerebrolysin with higher doses were also effective in nerve lesioned rats with NPs intoxication. These observations suggest that cerebrolysin actively protects spinal cord pathology and hyperalgesia following nerve lesion and its exacerbation with metal NPs, not reported earlier.

Oxygen desaturation in a transgender man: initial concerns and recommendations regarding the practice of chest binding: a case report.

BACKGROUND: Over 1.4 million US adults identify as transgender when gender identity differs from the sex assigned at birth [1]. Although transgender patients face adverse health outcomes, they remain an understudied population [2]. A 2017 study surveyed 411 practicing clinicians and found that 80% had been involved in treating a transgender patient, but 80.6% had never received training on transgender care [3]. The purpose of this report is to describe prolonged desaturation in one case of a transgender patient who wore a chest binder intraoperatively owing to a lack of preoperative recognition. CASE PRESENTATION: A 19-year-old transgender male of African-American descent with anxiety and class 3 obesity presented for an esophagogastroduodenoscopy to evaluate a 2-year history of upper abdominal pain unresponsive to proton pump inhibitor therapy, with a plan for monitored anesthesia care. His medications included sertraline, pantoprazole, zolpidem, ergocalciferol, leuprolide, and testosterone cypionate. Preoperatively, the patient was instructed to remove all clothing and to don a patient gown while in the bathroom. The attending anesthesiologist then conducted the interview and examination in the preoperative holding area. The patient was induced with 250 mg of propofol, and reassuring respirations were noted by capnography. Respirations and oxygen saturation remained stable upon insertion of the endoscope. Four minutes later, the patient's oxygen saturation rapidly decreased to 50% and end-tidal capnography was lost. The endoscope was removed, and the patient was given 200 mg of propofol and 20 mg succinylcholine. His oxygen saturation recovered to 80% and 100% after 2 and 5 minutes, respectively, of ventilation with 100% inspired oxygen. No further oxygen desaturation was noted throughout the procedure, and the patient was closely monitored for signs of respiratory difficulty during an uneventful postoperative course. After full emergence, it was revealed that the patient had been wearing a chest binder throughout the operative procedure. The patient was counseled on the necessity to communicate the presence of this accessory prior to all future procedures. CONCLUSION: In the clinical narrative, a healthy patient was observed to have prolonged oxygen desaturation after induction of anesthesia. Laryngospasm was suspected clinically owing to the sudden absence of end-tidal carbon dioxide. Prolonged oxygen desaturation despite appropriate interventions suggests the contribution of additional factors. We speculate that the presence of a chest binder intraoperatively predisposed the patient to more rapid oxygen desaturation less responsive to typical therapy. A chest binder would introduce mechanical restriction to the patient's breathing owing to its inherent design to compress. Although the patient was asked to remove all clothing, specific instructions were not provided regarding the removal of a chest binder. The presence of chest binding was also absent in the electronic health record, despite the documented presence of the patient's preferred gender, hormonal therapy regimen, and medical history. Ultimately, this case reflects the gap between practitioner knowledge and hospital guidelines and the practices of transgender patients. In reviewing existing literature and the potential for atelectasis with external compression, we would consider that patients refrain from chest binding for 12-24 hours before surgical procedures, resume no sooner than 24 hours after ambulation, and participate in diagnostic incentive spirometry pre- and postoperatively.

Persistent coagulopathy after gunshot traumatic brain injury: the importance of INR and the SPIN score.

INTRODUCTION: Penetrating ballistic brain injury (gunshot traumatic brain injury or GTBI) is associated with a high mortality. Admission Glascow Coma Scale (GCS), injury severity score and neurological findings, cardiopulmonary instability, coagulopathy and radiological finding such as bullet trajectory and mass effect are shown to predict survival after GTBI. We aimed to examine the dynamics of the observed coagulopathy and its association with outcome. METHODS: In this single-centered retrospective cohort study, we examined 88 patients with GTBI between 2015 and 2021. Variables analyzed include patient age; temperature, hemodynamic and respiratory variables, admission Glasgow Coma Scale (GCS); injury severity score (ISS); head abbreviated injury scale (AIS); Marshall, Rotterdam, SPIN and Baylor scores, and laboratory data including PTT, INR and platelet count. Receiver operating characteristic analysis was conducted to evaluate the performance of the predictive models. RESULTS: The average age of our sample was 28.5 years and a majority were male subjects (92%). Fifty-four (62%) of the patients survived to discharge. The GCS score, as well as the motor, verbal, and eye-opening sub-scores were higher in survivors (P < 0.001). As was expected, radiologic findings including the Marshall and Rotterdam Scores were also associated with survival (P < 0.001). Although the ISS and Head AIS scores were higher (P < 0.001), extracranial injuries were not more prevalent in non-survivors (P= 0.567). Non-survivors had lower platelet counts and elevated PTT and INR (P < 0.001) on admission. PTT normalized within 24 h but INR continued to increase in non-survivors. SPIN score, which includes INR, was a better predictor for mortality than Rotterdam, Marshall, and Baylor etc. CONCLUSION: Progressively increasing INR after GTBI is associated with poor outcome and may indicate consumption coagulopathy from activation of the extrinsic pathway of coagulation and metabolic derangements that are triggered and sustained by the brain injury. The SPIN score, which incorporates INR as a major survival score component, outperforms other available prediction models for predicting outcome after GTBI.

Alzheimer's disease neuropathology is exacerbated following traumatic brain injury. Neuroprotection by co-administration of nanowired mesenchymal stem cells and cerebrolysin with monoclonal antibodies to amyloid beta peptide.

Military personnel are prone to traumatic brain injury (TBI) that is one of the risk factors in developing Alzheimer's disease (AD) at a later stage. TBI induces breakdown of the blood-brain barrier (BBB) to serum proteins into the brain and leads to extravasation of plasma amyloid beta peptide (ΑßP) into the brain fluid compartments causing AD brain pathology. Thus, there is a need to expand our knowledge on the role of TBI in AD. In addition, exploration of the novel roles of nanomedicine in AD and TBI for neuroprotection is the need of the hour. Since stem cells and neurotrophic factors play important roles in TBI and in AD, it is likely that nanodelivery of these agents exert superior neuroprotection in TBI induced exacerbation of AD brain pathology. In this review, these aspects are examined in details based on our own investigations in the light of current scientific literature in the field. Our observations show that TBI exacerbates AD brain pathology and TiO2 nanowired delivery of mesenchymal stem cells together with cerebrolysin-a balanced composition of several neurotrophic factors and active peptide fragments, and monoclonal antibodies to amyloid beta protein thwarted the development of neuropathology following TBI in AD, not reported earlier.

Treatment Options for COVID-19-Related Guillain-Barré Syndrome: A Systematic Review of Literature.

BACKGROUND: Central nervous system complications are reported in an increasing number of patients with Coronavirus Disease 2019 (COVID-19). COVID-19-related Guillain-Barré syndrome (GBS) is of particular importance given its association with higher mortality rates and prolonged respiratory failure. REVIEW SUMMARY: We conducted a systematic review of published cases for COVID-19-related GBS, and provide a summary of clinical management strategies for these cases. Sixty-three studies, including 86 patients, were included. Seventy-six cases with reported outcome data were eligible for the outcome analysis. Ninety-nine percent of patients were diagnosed with COVID-19 before diagnosis of GBS (median: 14 d prior, interquartile range: 7 to 20). Intravenous immunotherapy (intravenous immunoglobulin: 0.4 g/kg/d for 5 d) was the most frequently used treatment approach. The review indicated that the outcome was not favorable in 26% of cases (persistent neurological deficits). A mortality rate of 3.5% was observed in patients with COVID-19-related GBS. CONCLUSIONS: Although evidence to support specific treatments is lacking, clinicians should consider the benefits of immunotherapy and plasma exchange in addition to the standard antimicrobial and supportive therapies for patients who meet the diagnostic criteria for acute sensory and motor polyradiculoneuritis. Intravenous immunoglobulin treatment alone is not shown to result in improved outcomes or mortality. More extensive studies aimed at exploring the neurological manifestations and complications of COVID-19 and distinctive treatment options for COVID-19-related GBS are warranted.