Analysis of appropriateness and safety when discharging patients on triple-antithrombotic therapies.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: To analyze the appropriateness of triple-antithrombotic therapy based on the 2020 American College of Cardiology (ACC) consensus statement while evaluating safety outcomes for patients with respect to adverse events. METHODS: A single-center, retrospective chart review was conducted using electronic medical records from December 18, 2020, to August 31, 2022. The primary endpoint was the rate of appropriateness for triple-antithrombotic therapy in patients discharged from Ochsner LSU Health Shreveport. Appropriateness was a composite endpoint extrapolated from the 2020 ACC consensus statement. For therapy to be defined as appropriate, patients had to have had the correct therapy indication, medications, dosing, and 30-day duration. Secondary safety endpoints included the percentage of patients rehospitalized at 14 and 30 days, the rate of major bleeding events, and the percentage of patients on gastrointestinal prophylaxis while on triple-antithrombotic therapy. RESULTS: A total of 93 patients were included in the study, of whom 31 (33%) received appropriate triple-antithrombotic therapy. Prolonged duration of triple-antithrombotic therapy was the most common reason that therapy did not meet the primary endpoint. The readmission rate due to bleeding was 2.2% at 14 days and 6.5% at 30 days. Within 30 days of initiation of triple therapy, 4.3% of patients endured major bleeding as defined by the International Society on Thrombosis and Hemostasis and 2 patients died. CONCLUSION: In this single-center study, triple-antithrombotic therapy appropriately adhered to the 2020 ACC consensus statement for one-third of patients discharged on this therapy.

Ecological correlates of three-dimensional muscle architecture within the dietarily diverse Strepsirrhini.

Analysis of muscle architecture, traditionally conducted via gross dissection, has been used to evaluate adaptive relationships between anatomical form and behavioral function. However, gross dissection cannot preserve three-dimensional relationships between myological structures for analysis. To analyze such data, we employ diffusible, iodine-based contrast-enhanced computed tomography (DiceCT) to explore the relationships between feeding ecology and masticatory muscle microanatomy in eight dietarily diverse strepsirrhines: allowing, for the first time, preservation of three-dimensional fascicle orientation and tortuosity across a functional comparative sample. We find that fascicle properties derived from these digital analyses generally agree with those measured from gross-dissected conspecifics. Physiological cross-sectional area was greatest in species with mechanically challenging diets. Frugivorous taxa and the wood-gouging species all exhibit long jaw adductor fascicles, while more folivorous species show the shortest relative jaw adductor fascicle lengths. Fascicle orientation in the parasagittal plane also seems to have a clear dietary association: most folivorous taxa have masseter and temporalis muscle vectors that intersect acutely while these vectors intersect obliquely in more frugivorous species. Finally, we observed notably greater magnitudes of fascicle tortuosity, as well as greater interspecific variation in tortuosity, within the jaw adductor musculature than in the jaw abductors. While the use of a single specimen per species precludes analysis of intraspecific variation, our data highlight the diversity of microanatomical variation that exists within the strepsirrhine feeding system and suggest that muscle architectural configurations are evolutionarily labile in response to dietary ecology-an observation to be explored across larger samples in the future.

Augmented Reality in Neurosurgery: A New Paradigm for Training.

Augmented reality (AR) involves the overlay of computer-generated images onto the user's real-world visual field to modify or enhance the user's visual experience. With respect to neurosurgery, AR integrates preoperative and intraoperative imaging data to create an enriched surgical experience that has been shown to improve surgical planning, refine neuronavigation, and reduce operation time. In addition, AR has the potential to serve as a valuable training tool for neurosurgeons in a way that minimizes patient risk while facilitating comprehensive training opportunities. The increased use of AR in neurosurgery over the past decade has led to innovative research endeavors aiming to develop novel, more efficient AR systems while also improving and refining present ones. In this review, we provide a concise overview of AR, detail current and emerging uses of AR in neurosurgery and neurosurgical training, discuss the limitations of AR, and provide future research directions. Following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 386 articles were initially identified. Two independent reviewers (GH and AC) assessed article eligibility for inclusion, and 31 articles are included in this review. The literature search included original (retrospective and prospective) articles and case reports published in English between 2013 and 2023. AR assistance has shown promise within neuro-oncology, spinal neurosurgery, neurovascular surgery, skull-base surgery, and pediatric neurosurgery. Intraoperative use of AR was found to primarily assist with surgical planning and neuronavigation. Similarly, AR assistance for neurosurgical training focused primarily on surgical planning and neuronavigation. However, studies included in this review utilize small sample sizes and remain largely in the preliminary phase. Thus, future research must be conducted to further refine AR systems before widespread intraoperative and educational use.

Protamine folds DNA into flowers and loop stacks.

DNA in sperm undergoes an extreme compaction to almost crystalline packing levels. To produce this dense packing, DNA is dramatically reorganized in minutes by protamine proteins. Protamines are positively charged proteins that coat negatively charged DNA and fold it into a series of toroids. The exact mechanism for forming these ∼50-kbp toroids is unknown. Our goal is to study toroid formation by starting at the "bottom" with folding of short lengths of DNA that form loops and working "up" to more folded structures that occur on longer length scales. We previously measured folding of 200-300 bp of DNA into a loop. Here, we look at folding of intermediate DNA lengths (L = 639-3003 bp) that are 2-10 loops long. We observe two folded structures besides loops that we hypothesize are early intermediates in the toroid formation pathway. At low protamine concentrations (∼0.2 µM), we see that the DNA folds into flowers (structures with multiple loops that are positioned so they look like the petals of a flower). Folding at these concentrations condenses the DNA to 25% of its original length, takes seconds, and is made up of many small bending steps. At higher protamine concentrations (≥2 µM), we observe a second folded structure-the loop stack-where loops are stacked vertically one on top of another. These results lead us to propose a two-step process for folding at this length scale: 1) protamine binds to DNA, bending it into loops and flowers, and 2) flowers collapse into loop stacks. These results highlight how protamine uses a bind-and-bend mechanism to rapidly fold DNA, which may be why protamine can fold the entire sperm genome in minutes.

Systematic Review of Research, Mentorship, and Career Resources for Medical Students Pursuing Neurosurgical Training.

BACKGROUND: Medical students are important team members and future healthcare providers in neurosurgery or other medical fields. We performed a systematic review evaluating studies assessing medical student guidance, mentorship, and career development in neurosurgery. The study aimed to identify the best practices and acknowledge gaps requiring improvement. METHODS: A systematic review of 586 research studies evaluating important aspects of medical student career development in neurosurgery was performed. The studies were analyzed for evidence supporting specific strategies to foster career development. RESULTS: A total of 45 studies were identified and categorized into 8 categories: 1) medical student interest groups; 2) student fellowships and institutional programs; 3) research and observership funding; 4) medical student research and scholarship; 5) student-led interest groups; 6) student mentorship; 7) educational resources; and 8) diversity, equity, and inclusion for medical students. Studies supported the significant positive effects of career resources for medical students, which often resulted in higher publication quantities, increased interest in the field, and greater ease of matriculation into a neurosurgical residency. One central gap included limited formal opportunities at many institutions, including medical schools without neurosurgery programs. Additional gaps were an absent structure for many forms of mentorship and delayed engagement of medical students in neurosurgical training, which significantly affects career interests. The currently available resources for these aspects of career development are listed. CONCLUSIONS: These studies highlight the current endeavors to encourage medical student careers. However, ample gaps and missed opportunities were also identified. Further work at both institutional and national levels is needed to improve the current environment.

Woven Endobridge embolization: Indications and innovation.

The treatment of intracranial aneurysms has seen incredible advancements over the last few decades. Long-term occlusion of wide-neck bifurcation aneurysms remains technically challenging. The Woven Endobridge (WEB) embolization device is innovative in its construction and uses. The design of the device has evolved over the last decade. Pre-clinical and clinical trials are ongoing and continue to inform the development of intrasaccular flow-diverting devices. The WEB device is currently approved by the U.S. Food and Drug Administration (FDA) for treating wide-neck aneurysms. The safety and efficacy of the WEB device have yielded promising clinical results that may have additional indications. This review aims to discuss the development of the WEB device and the current state of the WEB device in the treatment of wide-neck aneurysms. We also summarize ongoing clinical studies and potential innovative uses.

Ligand-Gated Ion Channels: Prognostic and Therapeutic Implications for Gliomas.

Gliomas are common primary brain malignancies that remain difficult to treat due to their overall aggressiveness and heterogeneity. Although a variety of therapeutic strategies have been employed for the treatment of gliomas, there is increasing evidence that suggests ligand-gated ion channels (LGICs) can serve as a valuable biomarker and diagnostic tool in the pathogenesis of gliomas. Various LGICs, including P2X, SYT16, and PANX2, have the potential to become altered in the pathogenesis of glioma, which can disrupt the homeostatic activity of neurons, microglia, and astrocytes, further exacerbating the symptoms and progression of glioma. Consequently, LGICs, including purinoceptors, glutamate-gated receptors, and Cys-loop receptors, have been targeted in clinical trials for their potential therapeutic benefit in the diagnosis and treatment of gliomas. In this review, we discuss the role of LGICs in the pathogenesis of glioma, including genetic factors and the effect of altered LGIC activity on the biological functioning of neuronal cells. Additionally, we discuss current and emerging investigations regarding the use of LGICs as a clinical target and potential therapeutic for gliomas.

Complementary Medicine and Expressive Arts Therapy: Adjuvant for Recovery Following Neurosurgical Procedures.

Art as a way of healing is primordial in many cultures. Expressive Arts Therapy (ExAT) uses art, music, dance, and writing to help individuals navigate their healing journey. Patient self-expression as a mode of recovery has been observed in patients with Parkinson's disease, epilepsy, Amyotrophic Lateral Sclerosis (ALS) and cancer. Complementary medical approaches such as acupuncture and mindfulness have also demonstrated benefits in patients suffering from neurological injury. Complementary medicine and ExAT are not mainstream approaches following neurosurgical procedures. There are very few systematic studies evaluating the benefits of expressive arts in neurosurgery. Advances in telemedicine and mobile applications may facilitate the incorporation of complementary medicine and ExAT into patient recovery. The purpose of our study is to explore the use of complementary medicine and ExAT in neurosurgical recovery. We start with a brief introduction of ExAT followed by available treatments offered. We discuss the benefits of multidisciplinary care and emerging technologies and how they can facilitate incorporation of complementary medicine and ExAT in neurosurgery. Finally, we review several clinical studies that have demonstrated success in using complementary medicine. Our goal is to provide alternative approaches to neurosurgery recovery so that patients may receive with the best care possible.

Patient-Specific Risk Factors Associated With the Development of Hyperchloremia in a Neurocritical Care Intensive Care Unit.

BACKGROUND: Hypertonic sodium chloride (HTS) is used in intensive care unit (ICU) settings to manage cerebral edema, intracranial hypertension, and for the treatment of severe hyponatremia. It has been associated with an increased incidence of hyperchloremia; however, there is limited literature focusing on hyperchloremic risk in neurologically injured patients. Objective: The primary objective of this study was to determine risk factors associated with development of hyperchloremia in a neurocritical care (NCC) ICU population. METHODS: This was a retrospective case-control study performed in an adult NCC ICU and included patients receiving HTS. The primary outcome was to evaluate patient characteristics and treatments associated with hyperchloremia. Secondary outcomes included acute kidney injury and mortality. RESULTS: Overall, 133 patients were identified; patients who were hyperchloremic were considered cases (n = 100) and patients without hyperchloremia were considered controls (n = 33). Characteristics and treatments were evaluated with univariate analysis and a logistic regression model. In the multivariate model, APACHE II Score, initial serum osmolality, total 3% saline volume, and total 23.4% saline volume were significant predictors for hyperchloremia. In addition, patients with a serum chloride greater than 113.5 mEq/L were found to have a higher risk of acute kidney injury (AKI) (adjusted OR 3.15; 95% CI 1.10-9.04). CONCLUSIONS: This study demonstrated APACHE II Score, initial serum osmolality, and total 3% and 23.4% saline volumes were associated with developing hyperchloremia in the NCC ICU. In addition, hyperchloremia is associated with an increased risk of AKI.

A woman with temporal pain.

Giant cell arteritis (GCA) is a difficult diagnosis to make in the emergency department, requiring a temporal artery biopsy to confirm the disease. Here, we present a case of GCA diagnosed on bedside ultrasound in a patient with left-sided temporal pain, left-sided blurry vision, and a normal erythrocyte sedimentation rate. Of note, this patient was on anticoagulation for atrial fibrillation, which delayed a biopsy from being performed, making the ultrasound findings even more significant. This case study suggests that bedside ultrasound can be utilized in the diagnosis of GCA, offering a quick, easy, and safe imaging modality that is available in many emergency departments.

Sleep-Disturbance-Induced Microglial Activation Involves CRH-Mediated Galectin 3 and Autophagy Dysregulation.

Chronic sleep disturbances (CSDs) including insomnia, insufficient sleep time, and poor sleep quality are major public health concerns around the world, especially in developed countries. CSDs are major health risk factors linked to multiple neurodegenerative and neuropsychological diseases. It has been suggested that CSDs could activate microglia (Mg) leading to increased neuroinflammation levels, which ultimately lead to neuronal dysfunction. However, the detailed mechanisms underlying CSD-mediated microglial activation remain mostly unexplored. In this study, we used mice with three-weeks of sleep fragmentation (SF) to explore the underlying pathways responsible for Mg activation. Our results revealed that SF activates Mg in the hippocampus (HP) but not in the striatum and prefrontal cortex (PFc). SF increased the levels of corticotropin-releasing hormone (CRH) in the HP. In vitro mechanism studies revealed that CRH activation of Mg involves galectin 3 (Gal3) upregulation and autophagy dysregulation. CRH could disrupt lysosome membrane integrity resulting in lysosomal cathepsins leakage. CRHR2 blockage mitigated CRH-mediated effects on microglia in vitro. SF mice also show increased Gal3 levels and autophagy dysregulation in the HP compared to controls. Taken together, our results show that SF-mediated hippocampal Mg activation involves CRH mediated galectin 3 and autophagy dysregulation. These findings suggest that targeting the hippocampal CRH system might be a novel therapeutic approach to ameliorate CSD-mediated neuroinflammation and neurodegenerative diseases.

The Current State of Neurosurgery in Somaliland.

BACKGROUND: Surgical conditions account for as much as one third of the global burden of disease, yet 5 billion people worldwide do not have access to timely, affordable surgical care. These disparities in access to timely surgical care are most pronounced in low- and middle-income countries, where the availability of specialty surgical services such as neurosurgery are severely limited or completely absent. The African autonomous region of Somaliland, in the Horn of Africa, is one such region. METHODS: Discussions were conducted with key individuals in Somaliland to ascertain the current state of neurosurgery in Somaliland. RESULTS: The current state of neurosurgery in Somaliland was characterized. First, a background on the recent history of the republic and the surrounding region was furnished, which provides context for the challenging socioeconomic conditions in Somaliland. Brief biographical sketches were presented of local leaders and general surgeons who are actively working to improve economic and health conditions and who welcome opportunities to improve all health services, including neurosurgery. In addition, an overview was presented of new initiatives in capacity building in neurosurgery and sources of directed training and care in neurosurgery. CONCLUSIONS: This article provides the first-ever assessment of current neurosurgery-related activity in Somaliland. The article provides recommendations to guide the international neurosurgery community in future contributions.

DNA looping by protamine follows a nonuniform spatial distribution.

DNA looping plays an important role in cells in both regulating and protecting the genome. Often, studies of looping focus on looping by prokaryotic transcription factors like lac repressor or by structural maintenance of chromosomes proteins such as condensin. Here, however, we are interested in a different looping method whereby condensing agents (charge ≥+3) such as protamine proteins neutralize the DNA, causing it to form loops and toroids. We considered two previously proposed mechanisms for DNA looping by protamine. In the first mechanism, protamine stabilizes spontaneous DNA fluctuations, forming randomly distributed loops along the DNA. In the second mechanism, protamine binds and bends the DNA to form a loop, creating a distribution of loops that is biased by protamine binding. To differentiate between these mechanisms, we imaged both spontaneous and protamine-induced loops on short-length (≤1 µm) DNA fragments using atomic force microscopy. We then compared the spatial distribution of the loops to several model distributions. A random looping model, which describes the mechanism of spontaneous DNA folding, fit the distribution of spontaneous loops, but it did not fit the distribution of protamine-induced loops. Specifically, it failed to predict a peak in the spatial distribution of loops at an intermediate location along the DNA. An electrostatic multibinding model, which was created to mimic the bind-and-bend mechanism of protamine, was a better fit of the distribution of protamine-induced loops. In this model, multiple protamines bind to the DNA electrostatically within a particular region along the DNA to coordinate the formation of a loop. We speculate that these findings will impact our understanding of protamine's in vivo role for looping DNA into toroids and the mechanism of DNA condensation by condensing agents more broadly.

Protamine loops DNA in multiple steps.

Protamine proteins dramatically condense DNA in sperm to almost crystalline packing levels. Here, we measure the first step in the in vitro pathway, the folding of DNA into a single loop. Current models for DNA loop formation are one-step, all-or-nothing models with a looped state and an unlooped state. However, when we use a Tethered Particle Motion (TPM) assay to measure the dynamic, real-time looping of DNA by protamine, we observe the presence of multiple folded states that are long-lived (∼100 s) and reversible. In addition, we measure folding on DNA molecules that are too short to form loops. This suggests that protamine is using a multi-step process to loop the DNA rather than a one-step process. To visualize the DNA structures, we used an Atomic Force Microscopy (AFM) assay. We see that some folded DNA molecules are loops with a ∼10-nm radius and some of the folded molecules are partial loops-c-shapes or s-shapes-that have a radius of curvature of ∼10 nm. Further analysis of these structures suggest that protamine is bending the DNA to achieve this curvature rather than increasing the flexibility of the DNA. We therefore conclude that protamine loops DNA in multiple steps, bending it into a loop.