Haemophilus parainfluenza-Associated Aortic Root Abscess and Septic Embolic Stroke Post-transcatheter Aortic Valve Replacement: A Case Study.

We present a rare instance of aortic root abscess and septic embolic stroke due to Haemophilus parainfluenza in a 75-year-old male patient who had undergone a recent transcatheter aortic valve replacement. The patient initially presented with generalized weakness and altered mental status. Blood cultures grew Haemophilus parainfluenza. Brain imaging showed multiple infarcts with some areas of hemorrhagic conversion. Echocardiography demonstrated an aortic root abscess as well as vegetation on the tricuspid valve. Surgical correction was deemed high risk; hence, management involved intravenous (IV) antibiotics, resulting in the resolution of both symptoms and the abscess.

N-Glycosylation-induced pathologic protein conformations as a tool to guide the selection of biologically active small molecules.

Post-translational modifications such as protein N-glycosylation, significantly influence cellular processes. Dysregulated N-glycosylation, exemplified in Grp94, a member of the Hsp90 family, leads to structural changes and the formation of epichaperomes, contributing to pathologies. Targeting N-glycosylation-induced conformations offers opportunities for developing selective chemical tools and drugs for these pathologic forms of chaperones. We here demonstrate how a specific Grp94 conformation induced by N-glycosylation, identified previously via molecular dynamics simulations, rationalizes the distinct behavior of similar ligands. Integrating dynamic ligand unbinding information with SAR development, we differentiate ligands productively engaging the pathologic Grp94 conformers from those that are not. Additionally, analyzing binding site stereoelectronic properties and QSAR models using cytotoxicity data unveils relationships between chemical, conformational properties, and biological activities. These findings facilitate the design of ligands targeting specific Grp94 conformations induced by abnormal glycosylation, selectively disrupting pathogenic protein networks while sparing normal mechanisms.

Myocardial Infarction and Complete Heart Block in a Patient With Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery (ALCAPA).

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital malformation. We present a case of an elderly patient with ALCAPA presenting with complete heart block and non-ST-elevation myocardial infarction years after diagnosis and surgical correction. An 81-year-old female with a history of ALCAPA presented to the emergency department with chest pain and progressive mental deterioration. She was bradycardic and hypotensive. An electrocardiogram revealed a complete heart block. Troponin was 4.04 ng/mL. She received atropine and underwent transcutaneous pacing. Left heart catheterization revealed complete occlusion of the mid-left circumflex artery, which was intervened with balloon angioplasty and chronic total occlusion of the right coronary artery. She was supported with temporary transvenous pacing, did not require further pacing support, and was discharged home. Previous records unearthed that in 1988 she had presented with syncope and was diagnosed with ALCAPA, filling from right-to-left collaterals with large and ectatic coronaries. At the time, she underwent surgical correction with excision of the left coronary from the pulmonary artery and reimplantation in the left coronary cusp along the posterior aorta. She had remained asymptomatic after her surgery until this presentation. ALCAPA is extremely rare in adults. Insufficient collaterals to the left ventricle cause inadequate blood supply, leading to ischemia in adults, predisposing them to arrhythmias and risk of sudden death. Adults with ALCAPA remain at increased risk of adverse cardiac events later in life, requiring long-term monitoring.

Drug repurposing for parasitic protozoan diseases.

Protozoan parasites are major hazards to human health, society, and the economy, especially in equatorial regions of the globe. Parasitic diseases, including leishmaniasis, malaria, and others, contribute towards majority of morbidity and mortality. Around 1.1 million people die from these diseases annually. The lack of licensed vaccinations worsens the worldwide impact of these diseases, highlighting the importance of safe and effective medications for their prevention and treatment. However, the appearance of drug resistance in parasites continuously affects the availability of medications. The demand for novel drugs motivates global antiparasitic drug discovery research, necessitating the implementation of many innovative ways to maintain a continuous supply of promising molecules. Drug repurposing has come out as a compelling tool for drug development, offering a cost-effective and efficient alternative to standard de novo approaches. A thorough examination of drug repositioning candidates revealed that certain drugs may not benefit significantly from their original indications. Still, they may exhibit more pronounced effects in other disorders. Furthermore, certain medications can produce a synergistic effect, resulting in enhanced therapeutic effectiveness when given together. In this chapter, we outline the approaches employed in drug repurposing (sometimes referred to as drug repositioning), propose novel strategies to overcome these hurdles and fully exploit the promise of drug repurposing. We highlight a few major human protozoan diseases and a range of exemplary drugs repurposed for various protozoan infections, providing excellent outcomes for each disease.

Elsberg Syndrome With Albuminocytologic Dissociation - A Guillain-Barré Syndrome Mimic or Guillain-Barré Syndrome Variant?

Introduction: Elsberg Syndrome is a presumed infectious lumbosacral radiculitis, with or without accompanying lumbar myelitis, that is often attributed to herpes simplex virus type 2 (HSV-2). Case: A 58-year-old man presented with lower extremity anesthesia, ataxic gait, radiological evidence of radiculitis, and CSF albuminocytologic dissociation. Polymerase chain reaction testing of CSF confirmed HSV-2 infection. Conclusion: A variety of presentations are reported within the scope of Elsberg Syndrome, potentially with distinct disease mechanisms. Delayed onset of neurological symptoms after resolution of rash and absence of pleocytosis raises the possibility that some patients meeting criteria for Elsberg Syndrome have a post-infectious immune-mediated neuropathy. We advise a lower threshold for PCR testing of herpes viruses in patients with acute neuropathy and albuminocytologic dissociation, particularly in cases with early sacral involvement.

Gaucher's Disease in an Adult Male: A Case Report of a Rare Mutation.

Gaucher's disease is a rare autosomal recessive inborn error of metabolism. As the presentation of this disease is similar to more common diseases like malaria, portal hypertension, hematological disorders, and kala-azar, this rare disease may not be thought of as a differential diagnosis, and a high index of suspicion is required to avoid diagnostic delay. We report a case of type 1 Gaucher's disease in an adult male born out of a consanguineous marriage. He was from a region where the prevalence of infectious diseases and sickle cell anemia is high. He presented with abdominal distension, hepatosplenomegaly, and pancytopenia. Bone marrow biopsy showed the presence of Gaucher cells. Glucocerebrosidase levels showed decreased enzyme activity. The genetic study revealed a very rare mutation that has not been reported in the 1000 Genomes database till now. Retrospectively, the most important clue was his birth out of a consanguineous marriage of his parents.

Andexanet alfa therapy showed No increased rate of thromboembolic events in spontaneous intracranial hemorrhage patients: A multicenter electronic health record study.

•Intracranial hemorrhage accounts for two out of every three major intracranial hemorrhages.•Systemic anticoagulation is routinely prescribed for prevention of cerebrovascular accidents.•The FDA approved Andexanet alfa to treat life-threatening bleeding.•Andexanet alfa relationship to outcomes requires further investigation.

Frailty as a predictor of poor outcomes in patients with chronic subdural hematoma (cSDH): A systematic review of literature.

Objective: In recent years, frailty has been reported to be an important predictive factor associated with worse outcomes in neurosurgical patients. The purpose of the present systematic review was to analyze the impact of frailty on outcomes of chronic subdural hematoma (cSDH) patients. Methods: We performed a systematic review of literature using the PubMed, Cochrane library, Wiley online library, and Web of Science databases following PRISMA guidelines of studies evaluating the effect of frailty on outcomes of cSDH published until January 31, 2023. Results: A comprehensive literature search of databases yielded a total of 471 studies. Six studies with 4085 patients were included in our final qualitative systematic review. We found that frailty was associated with inferior outcomes (including mortality, complications, recurrence, and discharge disposition) in cSDH patients. Despite varying frailty scales/indices used across studies, negative outcomes occurred more frequently in patients that were frail than those who were not. Conclusions: While the small number of available studies, and heterogenous methodology and reporting parameters precluded us from conducting a pooled analysis, the results of the present systematic review identify frailty as a robust predictor of worse outcomes in cSDH patients. Future studies with a larger sample size and consistent frailty scales/indices are warranted to strengthen the available evidence. The results of this work suggest a strong case for using frailty as a pre-operative risk stratification measure in cSDH patients.

Artificial Intelligence as A Complementary Tool for Clincal Decision-Making in Stroke and Epilepsy.

Neurology is a quickly evolving specialty that requires clinicians to make precise and prompt diagnoses and clinical decisions based on the latest evidence-based medicine practices. In all Neurology subspecialties-Stroke and Epilepsy in particular-clinical decisions affecting patient outcomes depend on neurologists accurately assessing patient disability. Artificial intelligence [AI] can predict the expected neurological impairment from an AIS [Acute Ischemic Stroke], the possibility of ICH [IntraCranial Hemorrhage] expansion, and the clinical outcomes of comatose patients. This review article informs readers of artificial intelligence principles and methods. The article introduces the basic terminology of artificial intelligence before reviewing current and developing AI applications in neurology practice. AI holds promise as a tool to ease a neurologist's daily workflow and supply unique diagnostic insights by analyzing data simultaneously from several sources, including neurological history and examination, blood and CSF laboratory testing, CNS electrophysiologic evaluations, and CNS imaging studies. AI-based methods are poised to complement the other tools neurologists use to make prompt and precise decisions that lead to favorable patient outcomes.

Early tracheostomy in patients undergoing mechanical thrombectomy for acute ischemic stroke.

PURPOSE: Respiratory failure following mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is a known complication, and requirement of tracheostomy is associated with worse outcomes. Our objective is to evaluate characteristics associated with tracheostomy timing in AIS patients treated with MT. METHODS: The National Inpatient Sample was queried for adult patients treated with MT for AIS from 2016 to 2019. Baseline demographic characteristics, comorbidities, and inpatient outcomes were analyzed for associations in patients who received tracheostomy. Timing of early tracheostomy (ETR) was defined as placement before day 8 of hospital stay. RESULTS: Of 3505 AIS-MT patients who received tracheostomy, 915 (26.1%) underwent ETR. Patients who underwent ETR had shorter length of stay (LOS) (25.39 days vs 32.43 days, p < 0.001) and lower total hospital charges ($483,472.07 vs $612,362.86, p < 0.001). ETR did not confer a mortality benefit but was associated with less acute kidney injury (OR, 0.697; p = 0.013), pneumonia (OR, 0.449; p < 0.001), and sepsis (OR, 0.536; p = 0.002). CONCLUSION: An expected increase in complications and healthcare resource utilization is seen in AIS-MT patients receiving tracheostomy, likely reflecting the severity of patients' post-stroke neurologic injury. Among these high-risk patients, ETR was predictive of shorter LOS and fewer complications.

Constrictive Pericarditis from an Atraumatic Hemopericardium After Systemic Thrombolysis for a Massive Pulmonary Embolism.

Constrictive pericarditis most commonly results from fibrosis and adhesions of the parietal and visceral pericardium due to long-standing inflammation. Common etiologies include idiopathic, post-surgical, radiation injury and infectious etiologies including tuberculosis. Traumatic hemopericardium is a rare cause of constrictive pericarditis but atraumatic hemopericardium causing constrictive pericarditis has not been reported in the literature to date. We present a case of constrictive pericarditis from an atraumatic hemopericardium after systemic thrombolysis for a massive pulmonary embolism.

Treatment of an Elusive Symptomatic Sinus Pericranii: Case Report and Review of the Literature.

Sinus pericranii (SP) are abnormal vascular connections between extracranial scalp venous channels and intracranial dural sinuses. This vascular abnormality rarely results in significant sequelae, but in select cases, it can be symptomatic. We describe the case of a 7-year-old girl with an SP who experienced intermittent visual, motor, and sensory symptoms not previously described in the literature. Her symptoms resolved after surgical treatment of the SP. We propose a mechanism for her symptoms and the rationale for the role of neurosurgical intervention along with a review of the literature.

Frailty and outcomes in lacunar stroke.

BACKGROUND: Lacunar strokes (LS) are ischemic strokes of the small perforating arteries of deep gray and white matter of the brain. Frailty has been associated with greater mortality and attenuated response to treatment after stroke. However, the effect of frailty on patients with LS has not been previously described. OBJECTIVE: To analyze the association between frailty and outcomes in LS. METHODS: Patients with LS were selected from the National Inpatient Sample (NIS) 2016-2019 using the International Classification of Disease, 10th edition (ICD-10) diagnosis codes. The 11-point modified frailty scale (mFI-11) was used to group patients into severely frail and non-severely frail cohorts. Demographics, clinical characteristics, and complications were defined. Health care resource utilization (HRU) was evaluated by comparing total hospital charges and length of stay (LOS). Other outcomes studied were discharge disposition and inpatient death. RESULTS: Of 48,980 patients with LS, 10,830 (22.1%) were severely frail. Severely frail patients were more likely to be older, have comorbidities, and pertain to lower socioeconomic status categories. Severely frail patients with LS had worse clinical stroke severity and increased rates of complications such as urinary tract infection (UTI) and pneumonia (PNA). Additionally, severe frailty was associated with unfavorable outcomes and increased HRU. CONCLUSION: Severe frailty in LS patients is associated with higher rates of complications and increased HRU. Risk stratification based on frailty may allow for individualized treatments to help mitigate adverse outcomes in the setting of LS.

An Unusual Etiology of Aortic Insufficiency: A Case Report.

Identifying the etiology of aortic insufficiency (AI) is essential in the management of the patient with valvular heart disease. We report the case of a 34-year-old male who presented with New York Heart Association (NYHA) class IV symptoms. The physical exam was consistent with AI, which was confirmed on echocardiography. Interestingly, the trileaflet aortic valve (TAV) was comprised of three retracted cusps, a rarely cited anatomic abnormality yielding AI. The patient underwent an uncomplicated aortic valve replacement (AVR).

The Effect of Tranexamic Acid on the Outcome of Total Ankle Replacement.

BACKGROUND: Infection rates after total ankle replacement (TAR) are known to be greater than those after hip or knee arthroplasty. Swelling after TAR can make wound healing more difficult, which can lead to infection. Tranexamic acid (TXA) has been shown to minimize blood loss after surgery, improving healing outcomes. We aim to assess the effect of TXA on blood loss and wound complications in TAR. METHODS: The research looked retrospectively at patients who had TAR procedures between September 2014 and December 2019. The procedures were done using the anterior approach at a single hospital by two, foot and ankle surgeons. Tranexamic acid was given intraoperatively before the tourniquet was inflated. The surgeons did not use surgical drains. Pre and postoperative hemoglobin levels, outcome scores as well as post-operative complications were all documented. RESULTS: A total of 69 patients were included in the study with 33 of them receiving TXA. With a mean age of 67.2, we had 31 females and 38 males. Tranexamic acid was given in doses ranging from 1 gm to 2 gm. None of the patients required blood transfusions after surgery, and there was no statistically significant difference in pre and postoperative hemoglobin levels between the two groups. In the TXA group, there were fewer wound complications. The TXA group achieved better results compared to the non-TXA group (p=0.0130). CONCLUSION: Tranexamic acid is safe and effective in lowering postoperative bleeding and preserving hemostasis after deflating the tourniquet, reducing edema and postoperative wound problems such as breakdown and dehiscence.

Classifications and level of evidence trends from the most influential literature on thoracolumbar burst fractures: A bibliometric analysis.

Background: There are known classifications that describe thoracolumbar (TL) burst type injury but it is unclear which have the most influence on management. Our objective is to investigate the association of classification publications with the quantity and type of the most influential articles on TL burst fractures. Methods: Web of Science was searched, and exclusion and inclusion criteria were used to extract the top 100 cited articles on TL burst fractures. The effects on type, number, and other variables were separated into four eras as defined by four major classification publications. Results: 30 out of the top 100 articles represent level 1 or 2 evidence. The most influential journal was Spine, accounting for 35 articles and 4,537 citations. The highest number of articles (53) was published between the years 1995-2005, culminating with the Thoracolumbar Injury Severity Classification Score (TLICS) paper. After 2005, there was an increase in average citations per year. Following 2013, the number of highly influential articles decreased, and systematic reviews (SRs) became a larger proportion of the literature. There was a statistically significant increase in the level of 1 and 2 evidence articles with time until the publication of TLICS. The predictive value of time for higher levels of evidence was only seen in the pre-2005 years (AUC: 0.717, 95% CI 0.579-0.855, p = 0.002). Conclusions: In 1994, two articles marked the beginning of an era of highly influential TL burst fracture literature. The 2005 TLICS score was associated with a preceding increase in LOE and productivity. Following 2005, the literature saw a decrease in productivity and an increase in systematic review/meta-analysis (SR-MAs). These trends represent an increase in scholarly discussion that led to a systematic synthesis of the existing literature after publication of the 2005 TLICS article.

Frailty Status Is a More Robust Predictor Than Age of Spinal Tumor Surgery Outcomes: A NSQIP Analysis of 4,662 Patients.

OBJECTIVE: The present study aimed to evaluate the effect of baseline frailty status (as measured by modified frailty index-5 [mFI-5]) versus age on postoperative outcomes of patients undergoing surgery for spinal tumors using data from a large national registry. METHODS: The National Surgical Quality Improvement Program database was used to collect spinal tumor resection patients' data from 2015 to 2019 (n = 4,662). Univariate and multivariate analyses for age and mFI-5 were performed for the following outcomes: 30-day mortality, major complications, unplanned reoperation, unplanned readmission, hospital length of stay (LOS), and discharge to a nonhome destination. Receiver operating characteristic (ROC) curve analysis was used to evaluate the discriminative performance of age versus mFI-5. RESULTS: Both univariate and multivariate analyses demonstrated that mFI-5 was a more robust predictor of worse postoperative outcomes as compared to age. Furthermore, based on categorical analysis of frailty tiers, increasing frailty was significantly associated with increased risk of adverse outcomes. 'Severely frail' patients were found to have the highest risk, with odds ratio 16.4 (95% confidence interval [CI],11.21-35.44) for 30-day mortality, 3.02 (95% CI, 1.97-4.56) for major complications, and 2.94 (95% CI, 2.32-4.21) for LOS. In ROC curve analysis, mFI-5 score (area under the curve [AUC] = 0.743) achieved superior discrimination compared to age (AUC = 0.594) for mortality. CONCLUSION: Increasing frailty, as measured by mFI-5, is a more robust predictor as compared to age, for poor postoperative outcomes in spinal tumor surgery patients. The mFI-5 may be clinically used for preoperative risk stratification of spinal tumor patients.

Endovascular thrombectomy with and without preceding intravenous thrombolysis for treatment of large vessel anterior circulation stroke: A cross-sectional analysis of 50,000 patients.

INTRODUCTION: The safety and efficacy of intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) for large vessel occlusion stroke remains a highly contested and unanswered clinical question. We aim to characterize the clinical profile, complications, and discharge disposition of EVT patients treated with and without preceding IVT using a large, nationally-representative sample. METHODS: The National Inpatient Sample was queried from 2015 to 2018 to identify adult patients with anterior circulation stroke treated with EVT with and without preceding IVT. Multivariable logistic regression analysis and propensity-score matching were employed to assess adjusted associations with clinical endpoints and to address confounding by indication for IVT, respectively. RESULTS: Among 48,525 patients identified, 40.7% (n = 19,735) received IVT prior to EVT. On unadjusted analysis, patients treated with IVT bridging therapy experienced higher rates of intracranial hemorrhage (26% vs. 24%, p = 0.003) and routine discharge to home with or without services (33% vs. 27%, p < 0.001), a lower frequency of thromboembolic complications (3% vs. 5%, p < 0.001), and lower rates of extended hospital stays (eLOS) (20% vs. 24%, p < 0.001). Multivariable logistic regression analysis adjusting for demographic and baseline clinical characteristics demonstrated independent associations of IVT bridging therapy with intracranial hemorrhage (aOR 1.28, 95% CI 1.15, 1.43; p < 0.001), thromboembolic complications (aOR 0.66, 95% CI 0.53, 0.83; p < 0.001), routine discharge (aOR 1.27, 95% CI 1.15, 1.40; p < 0.001), and eLOS (aOR 0.76, 95% CI 0.68, 0.85; p < 0.001). Sensitivity testing confirmed these findings. CONCLUSION: Preceding IVT was associated with favorable functional outcomes following endovascular therapy. Prospective randomized clinical trials are warranted for further evaluation.

Chemical tools for epichaperome-mediated interactome dysfunctions of the central nervous system.

Diseases are a manifestation of how thousands of proteins interact. In several diseases, such as cancer and Alzheimer's disease, proteome-wide disturbances in protein-protein interactions are caused by alterations to chaperome scaffolds termed epichaperomes. Epichaperome-directed chemical probes may be useful for detecting and reversing defective chaperomes. Here we provide structural, biochemical, and functional insights into the discovery of epichaperome probes, with a focus on their use in central nervous system diseases. We demonstrate on-target activity and kinetic selectivity of a radiolabeled epichaperome probe in both cells and mice, together with a proof-of-principle in human patients in an exploratory single group assignment diagnostic study (ClinicalTrials.gov Identifier: NCT03371420). The clinical study is designed to determine the pharmacokinetic parameters and the incidence of adverse events in patients receiving a single microdose of the radiolabeled probe administered by intravenous injection. In sum, we introduce a discovery platform for brain-directed chemical probes that specifically modulate epichaperomes and provide proof-of-principle applications in their use in the detection, quantification, and modulation of the target in complex biological systems.

Fenestration of intracranial neurenteric cyst: A case report.

BACKGROUND: Neurenteric cysts are rare congenital lesions of endodermal origin which result from the failure of the neurenteric canal to close during embryogenesis. The majority of neurenteric cysts occur in the spinal cord, though in rare instances can occur intracranially, typically in the posterior fossa anterior to the pontomedullary junction (80%) or in the supratentorial region adjacent to the frontal lobes (20%). CASE DESCRIPTION: We present the case of a 75-year-old woman with an extra-axial cystic lesion centered in the premedullary cistern causing brainstem compression. The lesion was later histopathologically confirmed to be a neurenteric cyst. She presented initially with a 4-month history of worsening headache, dizziness, and unsteady gait. We performed a left retrosigmoid craniotomy for cyst fenestration/biopsy with the aid of operating microscope and stealth neuronavigation. Following the procedure, the patient recovered without complications or residual deficits. CONCLUSION: This case illustrates the successful fenestration of an intracranial neurenteric cyst with good clinical outcome. We present the pre- and post-operative imaging findings, a technical video of the procedure, histopathological confirmation, and a brief review of the relevant clinical literature on the topic.