Introduction Arterial pseudoaneurysms and arteriovenous fistulas of intracranial and extracranial vessels are an uncommon occurrence following blunt and penetrating trauma and are commonly treated by ...vessel sacrifice,dependent on collateral flow1‐3. Others have treated these cases with covered stents4 and flow diversion5. Advances in flow diversion technology have led to their use in other pathologies, including carotid cavernous fistulas6 and vertebral artery pseudoaneurysms7. We present a case of a traumatic arteriovenous fistula of the dominant vertebral artery requiring vessel preservation and reconstruction. Methods A 42‐year‐old male presented with a gunshot wound to the face below the right eye. Trauma imaging identified fractures of the right maxillary sinus and orbital floor. CTA of the head/neck showed a dominant right vertebral artery dissection and pseudoaneurysm with a non‐dominant left vertebral artery (VA), effectively ending in PICA. Results Due to the inefficient supply to the posterior circulation via the left VA, the decision was made to preserve and reconstruct the right VA and the patient was brought to the angiography suite. Angiographically, the patient was noted to have retrograde filling of the posterior circulation, basilar and right VA through the anterior circulation in injection of both ICAs, suggesting decreased antegrade flow from the injured right VA. The right VA was catheterized which showed a high‐flow, high‐grade arteriovenous fistula from the V3 segment with venous drainage into multiple extraspinal cervical and epidural cervical veins. This also identified the fistulous point at the location of the pseudoaneurysm on CTA. The diagnostic catheter was exchanged for a guide catheter, and a Phenom 27 microcatheter (Medtronic; Minneapolis, MN) was navigated into the basilar artery. A Duo microcatheter (Microvention; Aliso Viejo, CA)/Synchro 2 (Stryker; Kalamazoo, MI) standard microwire complex was used to identify the fistulous point and positioned for jailing. A Pipeline Flex 4.75×20mm (Medtronic; Minneapolis, MN) was deployed from the proximal V4 segment across the pseudoaneurysm with persistence of the AVF. A second Pipeline Flex 5×20mm was placed in telescoping fashion with persistence of the AVF. A third Pipeline Flex 5×16mm was placed in telescoping fashion and flow diversion was observed. Using the jailed catheter, the pseudoaneurysm and fistulous point were coil embolized using a combination of helical and 3D HydroSoft coils (Microvention; Aliso Viejo, CA) of varying sizes. Final angiogram demonstrated resolution of the high‐flow AVF, improvement of antegrade flow through the right vertebral artery, and a slow‐flow low‐grade fistulous communication with the posterior extraspinal cervical veins. There were no thromboembolic complications and the patient recovered well from the procedure. Follow‐up angiography at 2 months post‐treatment showed obliteration of the AVF with a small remnant pseudoaneurysm of the right V3 segment. Conclusions Flow diversion is viable in the setting of a traumatic arteriovenous fistula requiring reconstruction of the parent vessel.
Introduction
Basal cell carcinoma (BCC) is the most common malignancy in the United States. The majority of cases are identified in Non‐Hispanic Whites (NHW) and are far less demonstrated in patients ...of colour (POC). However, the Hispanic population represents a large and growing proportion of the US population, and skin cancer diagnoses in Hispanics are rising. Thus, the goal of this study is to examine clinicopathologic differences between BCC in Hispanics versus NHW.
Methods
A retrospective chart review of Hispanic and NHW patients with BCC at Los Angeles County + USC Medical Center from January 2018 to March 2020 was performed. In total, 101 BCC samples from the first 100 patients identified of Hispanic ancestry, as well as 50 BCC samples identified from the first 50 patients identifying as NHW, were included for analysis. Patient characteristics (age, sex, medical history, and ethnicity), as well as tumour characteristics (location, subtype, tumour depth, and perineural invasion), were collected. We used between subjects t‐tests for continuous variables, and chi‐square tests for categorical variables.
Results
In total, 151 specimens were collected amongst 122 subjects (79 Hispanics and 43 NHW patients). Among NHW, the majority of patients (74.4%) were men, but among the Hispanic population, the majority (68.4%) were female (p < 0.001). Prior history of other skin cancer was more common among NHW (67.4%) than Hispanics (31.6%) (p=<0.001). The Hispanic population had a significantly higher proportion of head and neck tumours (p = 0.0004) but a lower proportion of extremity tumours (p = 0.001) compared to NHW. Pigmented BCC was significantly more common among Hispanic patients (p < 0.01). Finally, within the Hispanic group, there was a significant association between sex and histology (p = 0.004), with Hispanic men demonstrating more aggressive mix histology compared to Hispanic women.
Discussion
Our study supports the notion that BCC disparities occur among POC compared to NHW. This includes variations in epidemiologic factors such as sex and past medical history, primary tumour location, and pathologic characteristics. Further research should be conducted to identify additional differences in skin cancer presentation in POC to reduce the gaps in skin cancer knowledge and care.
Our study supports the notion that BCC disparities occur among POC compared to NHW. This includes variations in epidemiologic factors such as sex and past medical history, primary tumour location, and pathologic characteristics. Further research should be conducted to identify additional differences in skin cancer presentation in POC to reduce the gaps in skin cancer knowledge and care.
The complexes Pt(mdt)2 (4; mdt = methyldithiolene, Me2C2S2 n−), Pt(adt)2 (5; adt = p-anisyldithiolene, (MeO-p-C6H4)2C2S2 n−), and Pd(adt)2 (10) have been prepared in yields of ≥90% via ...transmetalation reactions with the corresponding R2Sn(S2C2R′2) complexes (R = n Bu, R′ = Me; R = Me, R′ = −C6H4-p-OMe, 3). Intraligand C–S and C–Cchelate bond lengths (∼1.71 and ∼1.40 Å, respectively) obtained by X-ray crystallography show these compounds to be comprised of radical monoanions mdt•– and adt•–. The six-coordinate octahedral adducts Pt(adt)2(dppe) 6; dppe = 1,2-bis(diphenylphosphino)ethane, trans-Pt(adt)2(PMe3)2 (8), and trans-Pt(mdt)2(PMe3)2 (9) have also been prepared, and crystal structures reveal dithiolene ligands that are fully reduced ene-1,2-dithiolates (C–S and C–Cchelate = ∼1.77 and 1.35 Å, respectively). Reduction of the dithiolene ligand thus occurs to accommodate the +IV oxidation state typical of octahedral six-coordinate platinum. The cyclic voltammogram of 5 shows two fully reversible reductions at −0.11 and −0.84 V in CH2Cl2 (vs Ag/AgCl), attributed to successive (adt•– + e– → adt2–) processes, and a reversible oxidation at +1.01 V. The cyclic voltammogram of 9 shows two reversible oxidations at +0.38 and +0.86 V, which are assigned as successive (adt2– → adt•– + e–) oxidations. Consistent with their formulation as having fully reduced dithiolene ligands, the UV–vis spectra for 6, 8, and 9 show no low-energy absorptions below 700 nm, and the S K-edge XAS spectra of 6 and 8 show dithiolene sulfur that is reduced relative to that in 5. The introduction of PMe3 to 10 did not produce the palladium analogue of 8 but rather Pd(adt)(PMe3)2 (11). The reaction of PdCl2(PPh3)2 with Li2(mdt) produced a mixture of Pd(mdt)(PPh3)2 (12, 20%) and (Ph3P)Pd(μ-1,2-mdt-S,S′:S)2Pd(PPh3) (13, 28%), with the latter having C 2 symmetry with a Pd2S2 core structure folded along the S···S axis.
•Increasing evidence suggests that patients with cancer diagnoses may be particularly vulnerable to poor outcomes from COVID-19.•To our knowledge, this is the first such study to report on outcomes ...amongst a primarily Hispanic-American population of cancer patients with COVID-19.•Elevated ANC, AST, CRP, and LDH at time of admission were significantly associated with severe outcomes.While the patients in our study received a variety of treatments, none were found to improve the occurrence of severe outcomes based on multivariate correlation analysis
We conducted a retrospective analysis of cancer patients who presented to the hospital with COVID-19 infection at a safety-net hospital in Los Angeles, California, from March 2020 to June 2020. From a list of 1,163 COVID-19+ adult patients, we selected the first 50 patients with malignancy for a preliminary analysis. There were 23 males (46.0%) and 27 females (54.0%); the median age was 60.5 years (IQR 47 – 72). Thirty-nine (78.0%) of the patients were Hispanic. The most prevalent cancers were genitourinary (14, 28.0%), hematologic (11, 22.0%), and gastrointestinal (10, 20.0%). Twenty-one (42.0%) patients had active disease at COVID-19 diagnosis, while 25 (50.0%) had no evidence of disease (NED), and 4 (8.0%) were unknown. Over 1 in 3 admitted patients experienced a “severe outcome,” which was defined as critical level care (14, 34.1%), use of vasopressors (9, 22.0%), intubation (8, 19.5%), or death (5, 12.2%). Patients with severe outcomes were found to have statistically higher values of absolute neutrophil count (p = 0.005), aspartate aminotransferase (p = 0.049), high-sensitivity C-reactive protein, (p = 0.001) and lactate dehydrogenase (p = 0.040) on admission. Overall survival (OS) was not statistically different between those with hematologic versus solid malignancy nor between those with active disease versus remission (both p>0.05). Thirteen (81.3%) of the 16 patients who had cancer treatment in 2020 experienced delays in cancer therapy. Additional cases are being evaluated as the pandemic continues with the goal of identifying areas for potential intervention to improve outcomes in this at-risk population.
Middle meningeal artery embolization is an increasingly common procedure involved in the treatment of chronic subdural hematoma (cSDH) that can be an adjuvant intervention or an alternative to ...traditional medical or surgical therapies. Our review aims to summarize the mechanism, properties, and available clinical data for current and investigative embolic agents used for the treatment of cSDH. Pubmed, Scopus, and clinicaltrials.gov were searched for relevant studies and ongoing trials that examine middle meningeal artery embolization for cSDH. Particle agents, liquid embolic agents, and coil embolization are the common classes of embolic materials used in clinical practice and in ongoing trials. These embolic agents are not only mechanical occlusive materials; they have unique properties that address the angiogenic and proinflammatory mechanisms that propagate and sustain cSDH. Particle agents, such as polyvinyl alcohol and Embosphere (tris‐acryl gelatin microspheres) have been the most commonly used embolic agents given the long‐term evidence base regarding efficacy and established safety record. Liquid embolic agents such as cyanoacrylate glues and copolymer agents such as Onyx, Squid, and PHIL are increasingly common in clinical settings due to improved visualization on imaging, durable embolization, and better control of distal embolization. Coil embolization is used in conjunction with other embolic agents or as monotherapy in the setting of dangerous middle meningeal artery anastomoses. There are several ongoing randomized clinical trials and prospective cohort studies that will clarify the safety, efficacy, and use cases of particle agents, liquid embolic agents, and coil embolization for the treatment of cSDH.
•Pseudoaneurysm formation following cerebrovascular blunt trauma is a rarely experienced complication with an incidence rate of less than 1 %.•In craniofacial trauma, pseudoaneurysm formation is not ...apparent on physical examination due to its deep location and usually presents as persistent nasal bleeding.•A low threshold for diagnosing and treating such entities is essential for controlling the hemorrhage and preventing morbidity and mortality.•Endovascular embolization provides immediate blood control should be included as a primary treatment option or as an adjunct to the surgical approach.
Facial fractures, specifically orbitozygomatic and zygomaticomaxillary complex fractures, are well-documented and common injuries. Pseudoaneurysm formation following cerebrovascular blunt trauma is a rarely experienced complication with an incidence rate of less than 1% with only a few cases reported in the literature. Traumatic pseudoaneurysm formation of the sphenopalatine artery (SPA), the deepest branch of the maxillary artery, is extremely rare due to the deep location of the SPA and its protection from bony landmarks. In craniofacial trauma, pseudoaneurysm formation is not apparent on physical examination due to its deep location and usually presents as persistent nasal bleeding. SPA pseudoaneurysms can present as complications of surgical osteotomies, endoscopic sinus surgeries, facial trauma, or even as a progression of nasopharyngeal cancer. Endovascular embolization provides, safe, quick, and effective treatment while minimizing the morbidity of extensive surgical exposure. In this case report we describe a sphenopalatine artery pseudoaneurysm formation post trauma to provide insight to these rare entities and highlight the importance of early detection and treatment.
Aging is associated with complex molecular alterations at the cellular level. Bone marrow exhibits distinct phenotypic, genetic and epigenetic alterations with aging. Metabolic changes in the bone ...marrow related to aging have not been studied.
In this study, we characterized the metabolome and transcriptome of aging murine bone marrow and compared it with bone marrow from young healthy mice and chemotherapy treated mice; chemotherapy treatment is known to induce age-related changes in hematopoiesis.
The metabolome of the aging bone marrow exhibited a signature of suppressed fatty-acid oxidation: accumulation of free fatty acids, reduced acyl-carnitines and low β-hydroxy butyric acid. The aged bone marrow also exhibited a significant reduction in amino acid and nucleic acid pool. The transcriptome of the aging bone marrow revealed a signature of oxidative stress, known to be associated with mitochondrial dysfunction. Lastly, the metabolic and transcriptomic profiles of the bone marrow of chemotherapy treated mice did not show broad age-related changes but rather mostly resembled young healthy mice, suggestive of a lack of 'metabolic aging' with chemotherapy exposure.
Our results revealed broad changes in lipids, amino acids, and nucleotides in aging marrow tissue. Together, these data provide a rich resource for the study of metabolic changes associated with aging in bone marrow.
After emerging in China in late 2019, the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide, and as of mid-2021, it remains a significant threat ...globally. Only a few coronaviruses are known to infect humans, and only two cause infections similar in severity to SARS-CoV-2:
, a species closely related to SARS-CoV-2 that emerged in 2002, and
, which emerged in 2012. Unlike the current pandemic, previous epidemics were controlled rapidly through public health measures, but the body of research investigating severe acute respiratory syndrome and Middle East respiratory syndrome has proven valuable for identifying approaches to treating and preventing novel coronavirus disease 2019 (COVID-19). Building on this research, the medical and scientific communities have responded rapidly to the COVID-19 crisis and identified many candidate therapeutics. The approaches used to identify candidates fall into four main categories: adaptation of clinical approaches to diseases with related pathologies, adaptation based on virological properties, adaptation based on host response, and data-driven identification (ID) of candidates based on physical properties or on pharmacological compendia. To date, a small number of therapeutics have already been authorized by regulatory agencies such as the Food and Drug Administration (FDA), while most remain under investigation. The scale of the COVID-19 crisis offers a rare opportunity to collect data on the effects of candidate therapeutics. This information provides insight not only into the management of coronavirus diseases but also into the relative success of different approaches to identifying candidate therapeutics against an emerging disease.
The COVID-19 pandemic is a rapidly evolving crisis. With the worldwide scientific community shifting focus onto the SARS-CoV-2 virus and COVID-19, a large number of possible pharmaceutical approaches for treatment and prevention have been proposed. What was known about each of these potential interventions evolved rapidly throughout 2020 and 2021. This fast-paced area of research provides important insight into how the ongoing pandemic can be managed and also demonstrates the power of interdisciplinary collaboration to rapidly understand a virus and match its characteristics with existing or novel pharmaceuticals. As illustrated by the continued threat of viral epidemics during the current millennium, a rapid and strategic response to emerging viral threats can save lives. In this review, we explore how different modes of identifying candidate therapeutics have borne out during COVID-19.
Senescence, a state of permanent cell cycle arrest, can be induced by DNA damage. This process, which was initially described in fibroblasts, is now recognized to occur in stem cells. It has been ...well characterized in cell lines, but there is currently very limited data available on human senescence in vivo. We recently reported that the expression of transposable elements (TE), including endogenous retroviruses, was up-regulated along with inflammatory genes in human senescent hematopoietic stem and progenitor cells (HSPCs) in vivo. The mechanism of regulation of TE expression is not completely understood, but changes in DNA methylation and chromatin modifications are known to alter their expression. In order to elucidate the molecular mechanisms for TE up-regulation after senescence of HSPCs, we employed whole-genome bisulfite sequencing in paired senescent and active human HSPCs in vivo from healthy subjects. We found that the senescent HSPCs exhibited hypomethylated regions in the genome, which were enriched for TEs. This is the first report characterizing the methylome of senescent human HSPCs.
The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral ...species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus’s structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system’s protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease. IMPORTANCE COVID-19 involves a number of organ systems and can present with a wide range of symptoms. From how the virus infects cells to how it spreads between people, the available research suggests that these patterns are very similar to those seen in the closely related viruses SARS-CoV-1 and possibly Middle East respiratory syndrome-related CoV (MERS-CoV). Understanding the pathogenesis of the SARS-CoV-2 virus also contextualizes how the different biological systems affected by COVID-19 connect. Exploring the structure, phylogeny, and pathogenesis of the virus therefore helps to guide interpretation of the broader impacts of the virus on the human body and on human populations. For this reason, an in-depth exploration of viral mechanisms is critical to a robust understanding of SARS-CoV-2 and, potentially, future emergent human CoVs (HCoVs).
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