Cerebral Venous Sinus Thromboses in Patients with SARS-CoV-2 Infection: Three Cases and a Review of the Literature.

INTRODUCTION: Early studies suggest that acute cerebrovascular events may be common in patients with coronavirus disease 2019 (COVID-19) and may be associated with a high mortality rate. Most cerebrovascular events described have been ischemic strokes, but both intracerebral hemorrhage and rarely cerebral venous sinus thrombosis (CVST) have also been reported. The diagnosis of CVST can be elusive, with wide-ranging and nonspecific presenting symptoms that can include headache or altered sensorium alone. OBJECTIVE: To describe the presentation, barriers to diagnosis, treatment, and outcome of CVST in patients with COVID-19. METHODS: We abstracted data on all patients diagnosed with CVST and COVID-19 from March 1 to August 9, 2020 at Boston Medical Center. Subsequently, we reviewed the literature and extracted all published cases of CVST in patients with COVID-19 from January 1, 2020 through August 9, 2020 and included all studies with case descriptions. RESULTS: We describe the clinical features and management of CVST in 3 women with COVID-19 who developed CVST days to months after initial COVID-19 symptoms. Two patients presented with encephalopathy and without focal neurologic deficits, while one presented with visual symptoms. All patients were treated with intravenous hydration and anticoagulation. None suffered hemorrhagic complications, and all were discharged home. We identified 12 other patients with CVST in the setting of COVID-19 via literature search. There was a female predominance (54.5%), most patients presented with altered sensorium (54.5%), and there was a high mortality rate (36.4%). CONCLUSIONS: During this pandemic, clinicians should maintain a high index of suspicion for CVST in patients with a recent history of COVID-19 presenting with non-specific neurological symptoms such as headache to provide expedient management and prevent complications. The limited data suggests that CVST in COVID-19 is more prevalent in females and may be associated with high mortality.

Association between inflammatory biomarkers and neointimal response following elective implantation of the ABSORB bioresorbable vascular scaffold.

INTRODUCTION: The ABSORB bioresorbable vascular scaffold (BVS) is associated with greater neointimal proliferation and thrombotic rate than metal stent. The role of inflammatory biomarkers on neointimal proliferation has not been studied in the setting of BVS implantation. PATIENTS AND METHODS: Thirty patients had arterial blood sampling before elective percutaneous coronary intervention with the ABSORB BVS and at 9-months follow-up. Plasma levels of interleukin-6, soluble CD40 ligand, monocyte chemotactic protein-1 and C-reactive protein were measured using enzyme-linked immunosorbent assay. Baseline and follow-up levels were compared for each biomarker. Optical frequency domain imaging was performed at follow-up and the neointimal burden was calculated as the ratio of neointimal area to scaffold area. The levels of inflammatory mediators were correlated with the neointimal burden. RESULTS: There was no significant increase in the levels of biomarkers from baseline to follow-up. Median C-reactive protein levels changed from 1.1 [interquartile range (IQR): 0.5-2.5] to 2.2 (IQR: 0.5-3.5) µg/ml, interleukin-6 from 1.0 (IQR: 0.6-1.4) to 1.0 (IQR: 0.6-1.4) pg/ml, monocyte chemotactic protein-1 from 120.4 (IQR: 86.0-153.4) to 102.0 (IQR: 70.3-148.1) pg/ml and soluble CD40 ligand from 108.3 (IQR: 74.1-173.7) to 112.0 (IQR: 71.0-225.9) pg/ml. The average neointimal burden in the cohort was 18±6%. Baseline, follow-up and change in plasma levels of inflammatory markers between these two time points did not correlate with the neointimal burden. CONCLUSION: Elective percutaneous coronary intervention with the ABSORB BVS does not provoke a chronic inflammatory response. The degree of neointimal proliferation after elective implantation of the ABSORB BVS is independent of the pre-existing inflammatory environment.

A randomized trial comparing two stent sizing strategies in coronary bifurcation treatment with bioresorbable vascular scaffolds - The Absorb Bifurcation Coronary (ABC) trial.

BACKGROUND: Limited information is available on the use of Bioresorbable Vascular Scaffold (BVS) in bifurcations involving significant side branches. When treating bifurcation disease with metal stents, the recommendation is to choose a stent diameter based on the distal main vessel diameter. Whether this sizing strategy is applicable to BVS is currently unknown. METHODS: We randomised 37 patients undergoing elective PCI for 'false' bifurcation disease (Medina 0,1,0; 1,0,0; 1,1,0) to receive BVS based either on proximal or distal reference diameters. Optical Frequency Domain Imaging (OFDI) measurements were performed pre BVS insertion to obtain proximal and distal reference diameters and post implantation. BVS size was chosen according to the proximal or distal reference diameter as per randomisation. Implantation was performed using the PSP technique tailored to bifurcation stenting. OFDI was repeated post implantation to confirm satisfactory expansion and apposition. RESULTS: Baseline demographics between the two groups were similar. Patients were aged 62.8 ±â€¯3.3 years; 76% were male. Mean side branch diameter was 2.24 ±â€¯0.13 mm. TIMI III flow in the main vessel was achieved in all cases. Side branch occlusion occurred in 1 case (2.7%). In the distal-sizing arm, there was a greater incidence of significant malapposition (>300 µm) at the proximal end of the scaffold on OCT (2.3% versus 0.8%, p 0.023). The incidence of distal edge dissections was numerically greater in the proximal-sizing group but this was not statistically significant (31.3% vs 11.8%, p 0.17). CONCLUSION: Both proximal and distal sizing strategies have similar procedural complication rates when using the ABSORB BVS to treat coronary bifurcations. However a proximal sizing strategy is associated with less malapposition and may be preferable.

Brain-dead and pregnant in Texas.

When a Texas hospital continued ventilator support for a pregnant patient who met the neurological criteria for the determination of death, it acted against the wishes of the patient's husband and other family members. The hospital stated that its treatment decision was required under the Texas Advance Directives Act, in particular the "pregnancy exclusion" that instructs providers to continue life-sustaining treatment as long as the patient is pregnant, notwithstanding contrary instructions in the patient's living will or from the patient's surrogate decision-maker. Contrary to the hospital's stated position, however, neither the literal words of the pregnancy exclusion nor the Advance Directives Act read as a whole requires continued ventilator support once a pregnant patient is determined to be brain dead.

Healthcare epidemiology: active surveillance cultures and contact precautions for control of multidrug-resistant organisms: ethical considerations.

Infection control personnel are required to develop institutional guidelines for prevention of transmission of multidrug-resistant organisms, especially methicillin-resistant Staphylococcus aureus, within health care settings. Such guidelines include performance of active surveillance cultures for patients after admission to health care facilities or to high-risk-patient care units, to detect colonization with target multidrug-resistant organisms. Patients who are colonized with these potential pathogens are placed under contact precautions to prevent transmission to other patients. Such screening programs are labor and resource intensive and raise the following ethical considerations: (1) autonomy versus communitarianism, (2) indication for informed consent for obtainment of active surveillance cultures, and (3) identification of the appropriate payer. Relevant infection control, public health, and ethical principles are reviewed in an effort to provide guidance for ethical decision making when designing a multidrug-resistant organism control program that includes active surveillance cultures and contact precautions. We conclude that a program of active surveillance cultures and contact precautions is part of standard medical care that requires patient education but not a specific informed consent and that the cost for such programs should be assigned to the health care institution, not the individual patient.

Genome-wide analysis identifies interleukin-10 mRNA as target of tristetraprolin.

Tristetraprolin (TTP) is an RNA-binding protein required for the rapid degradation of mRNAs containing AU-rich elements. Targets regulated by TTP include the mRNAs encoding tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, interleukin-2 (IL-2), and immediate early response 3. To identify novel target mRNAs of TTP in macrophages, we used a genome-wide approach that combines RNA immunoprecipitation and microarray analysis. A list was compiled of 137 mRNAs that are associated with TTP with an estimated accuracy on the order of 90%. Sequence analysis revealed a highly significant enrichment of AU-rich element motifs, with AUUUA pentamers present in 96% and UUAUUUAUU nonamers present in 44% of TTP-associated mRNAs. We further show that IL-10 is a novel target regulated by TTP. IL-10 mRNA levels were found to be elevated because of a reduced decay rate in primary macrophages from TTP(-/-) mice. Our study demonstrates the importance of experimental approaches for identifying targets of RNA-binding proteins.

ARE-mRNA degradation requires the 5'-3' decay pathway.

As an important mode of suppressing gene expression, messenger RNAs containing an AU-rich element (ARE) in the 3' untranslated region are rapidly degraded in the cytoplasm. ARE-mediated mRNA decay (AMD) is initiated by deadenylation, and in vitro studies have indicated that subsequent degradation occurs in the 3'-5' direction through a complex of exonucleases termed the exosome. An alternative pathway of mRNA degradation occurs at processing bodies, cytoplasmic foci that contain decapping enzymes, the 5'-3' exonuclease Xrn1 and the Lsm1-7 heptamer. To determine which of the two pathways is important for AMD in live cells, we targeted components of both pathways using short interfering RNA in human HT1080 cells. We show that Xrn1 and Lsm1 are essential for AMD. On the other side, out of three exosome components tested, only knockdown of PmScl-75 caused a strong inhibition of AMD. Our results show that mammalian cells, similar to yeast, require the 5'-3' Xrn1 pathway to degrade ARE-mRNAs.

Medical futility in the neonatal intensive care unit: hope for a resolution.

Contemporary medical practice in the NICU sometimes leads to conflicts between providers and parents in which the parent demands continuation of life-sustaining treatment that the medical team deems medically inappropriate or futile. Such conflicts can be difficult to resolve and trying for all parties. Here we describe a conflict involving a 25-week-gestation, 825-g newborn with multiple intractable medical problems and resolution of the conflict through ethics consultation under provisions of the Texas Advance Directives Act. The process established under Texas law sets conceptual and temporal boundaries around the problem of medical futility and provides a legal safe harbor for physicians who seek to withdraw life-sustaining treatments in the setting of medical futility, allowing resolution of such conflicts in a timely and effective manner. As such, it may provide a model for physicians in other states to follow.

Health insurance and cardiac transplantation: a call for reform.

Cardiac transplantation is an accepted therapy for patients with end-stage heart failure (ESHF). Presently in the U.S., patients with ESHF need to have health insurance or another funding source to be considered eligible for cardiac transplantation. Whether it is appropriate to exclude potential recipients solely due to lack of finances has received considerable interest including being the subject of a recent major motion picture (John Q, New Line Cinema, 2002). However, one important aspect of this debate has been underappreciated and insufficiently addressed. Specifically, organ donation does not require the donor to have health insurance. Thus, individuals donate their hearts although they themselves would not have been eligible to receive a transplant had they needed one. By querying Siminoff's National Study of Family Consent to Organ Donation database, we find that this situation is not uncommon as approximately 23% of organ donors are uninsured. Herein we also discuss how the funding requirement for cardiac transplantation has been addressed by the federal government in the past, its implications on the organ donor consent process, and its potential impact on organ donation rates. We call for a government-sponsored, multidisciplinary task force to address this situation in hopes of remedying the inequities in the present system of organ allocation.

Living and dying in a post-Schiavo world.

The tragic circumstances surrounding the death of Theresa Marie Schiavo have reignited discussion regarding end-of-life decisionmaking. In this Article, the author examines the current legal and ethical environment surrounding the decision to end life-sustaining treatment. Starting with the New Jersey Supreme Court's decision in In re Quinlan, the author discusses how such important issues as who should be the surrogate decisionmaker, attitudes towards artificial nutrition and dehydration, and difficulties in defining medical futility. Looking through a post-Schiavo lens, the Article examines state law addressing these issues and how these choices may be reexamined in the coming years.

Resolution of futility by due process: early experience with the Texas Advance Directives Act.

Every U.S. state has developed legal rules to address end-of-life decision making. No law to date has effectively dealt with medical futility--an issue that has engendered significant debate in the medical and legal literature, many court cases, and a formal opinion from the American Medical Association's Council on Ethical and Judicial Affairs. In 1999, Texas was the first state to adopt a law regulating end-of-life decisions, providing a legislatively sanctioned, extrajudicial, due process mechanism for resolving medical futility disputes and other end-of-life ethical disagreements. After 2 years of practical experience with this law, data collected at a large tertiary care teaching hospital strongly suggest that the law represents a first step toward practical resolution of this controversial area of modern health care. As such, the law may be of interest to practitioners, patients, and legislators elsewhere.