Faculty Bibliography

Purpose: African American (AA) patients are at risk for increased rates of rejection after heart transplantation (HT).We compared cell-free DNA (cf-DNA) levels after HT by recipient race.
Method(s): This was a retrospective analysis of 96 HT recipients from the Genomic Research Alliance for Transplantation (GRAFT) Registry, of which 63 patients had cf-DNA values. Cf-DNA values were compared by race withan exponential decay model and Kaplan-Meier (KM) analysis was performed to compare time-to-first rejection.
Result(s): Compared to non-AA patients, AA recipients had a similar prevalence of diabetes and hypertension,proportion of males, and donor characteristics. AA recipients had higher cf-DNA values compared to non-AA recipients for the first five days following transplant (8.3% vs. 3.2% p=0.001 Table 1/figure 1). The stable state cf-DNA values decayed rapidly for AA patients and equalized to non-AA patients over the first 7 days (0.46% vs 0.45%, p=0.8 Table 1). Cellular rejection did not differ by race (HR [CI]=1.4 [0.62,3.2], p=0.4). However AA were at higher risk of antibody mediated rejection (HR [CI]=3.8 [1.3,10.9], p=0.01).
Conclusion(s): African American patients had increased cf-DNA values in the first week following heart transplant. This may be a marker of early injury contributing to increased rates of allograft rejection in AA patients. Further analysisadjusting for confounding variables and determining predictors of clinical outcomes will be included at the time of presentation once follow-up of the GRAFT registry is complete.
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BACKGROUND AND PURPOSE/OBJECTIVE:Coronavirus disease 2019 (COVID-19) appears to be an independent risk factor for stroke. We hypothesize that patients who develop stroke while hospitalized for severe COVID-19 will have higher inflammatory markers and distinct stroke imaging patterns compared with patients positive for COVID-19 with out-of-hospital stroke onset and milder or no COVID-19 symptoms. MATERIALS AND METHODS/METHODS:This is a retrospective case series of patients positive for COVID-19 on polymerase chain reaction testing with imaging-confirmed stroke treated within a large health care network in New York City and Long Island between March 14 and April 26, 2020. Clinical and laboratory data collected retrospectively included complete blood counts and creatinine, alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer levels. All CT and MR imaging studies were independently reviewed by 2 neuroradiologists who recorded stroke subtype and patterns of infarction and intracranial hemorrhage. RESULTS:< .003). CONCLUSIONS:Patients with stroke hospitalized with severe COVID-19 are characterized by higher inflammatory, coagulopathy, and tissue-damage biomarkers, supporting proposed pathogenic mechanisms of hyperinflammation activating a prothrombotic state. Cautious balancing of thrombosis and the risk of hemorrhagic transformation is warranted when considering anticoagulation.

BACKGROUND CONTEXT: Spinal fusion is increasingly considered for management of patients with osteoporosis (OP) and degenerative disc disease (DDD). Little data is available regarding long-term outcomes in OP patients undergoing short-segment, lumbar fusion for DDD. PURPOSE: Analyze the impact of OP on long-term outcomes in patients who have had 2-3-level lumbar fusions for degenerative disc disease. STUDY DESIGN/SETTING: Retrospective review of the New York State Statewide Planning and Research Cooperative System (NYS SPARCS) database. PATIENT SAMPLE: Patients with DDD undergoing 2-3-level lumbar fusion. OUTCOME MEASURES: Frequency of 2-year medical and surgical complications and reoperations.
METHOD(S): Utilizing SPARCS, all patients from 2009-2011 with ICD-9 codes for DDD who underwent 2-3-level lumbar fusion were identified. Patients with bone mineralization disorders, systemic and endocrine disorders affecting bone quality were excluded. Surgical indications of trauma, systemic disease(s), and infection were excluded. Patients with and without OP were compared for demographics, hospital-related parameters, and 2-year complications and reoperations. Logistic regression models were utilized to identify predictors of complications.
RESULT(S): A total of 29,028 patients (OP=1,353 (4.7%), No-OP=27,675) were included. OP patients were older (66.9 vs 52.6 years) as well as more often female (85.1% vs 48.4%) and white (82.8% vs 73.5%), all p<0.001. Deyo index did not differ between groups. LOS and total charges were higher for OP patients (4.9 vs 4.1 days; $74,484 vs $73,724), all p<0.001. Medical complications were higher for OP patients: acute renal failure (8.9% vs 4.7%), and deep vein thromboses (3.4% vs 1.6%), all p<0.01. OP patients also had higher rates of implant-related (3.4% vs 1.9%) and wound complications (9.8% vs 5.9%) (p<0.01). Preoperative OP was associated with 2-year medical and surgical complications (OR=1.62, 1.66; p<0.001). Patients with OP had greater odds of reoperations (OR=1.34).
CONCLUSION(S): Patients with OP undergoing 2-3-level lumbar fusion for DDD were at higher risk of 2-year medical and surgical complications, and 3.4% of OP patients experienced implant-related complication. These findings highlight the importance of rigorous preoperative metabolic workup prior to spinal surgery. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.
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BACKGROUND CONTEXT: MBDs are often implicated in or contribute to degenerative disc disease (DDD). Yet, there is limited long-term, postoperative outcome data on the impact of MBDs on 2-year outcomes following 2-3-level lumbar fusion for DDD. PURPOSE: To determine if DDD patients with MBDs have comparable outcomes to those without MBDs following lumbar fusion. STUDY DESIGN/SETTING: Retrospective cohort. PATIENT SAMPLE: New York State Statewide Planning and Research Cooperative System was reviewed from 2009-2013 to identify all patients with DDD who underwent short, lumbar fusion (2-3-levels) with >=2-year follow-up OUTCOME MEASURES: Two-year outcome rates (medical/surgical complications and reoperations).
METHOD(S): The New York State Statewide Planning and Research Cooperative System was reviewed from 2009-2013 to identify all patients with DDD who underwent short, lumbar fusion (2-3 levels) with >=2-year follow-up. Patients with and without MBD (vitamin D deficiency, hyperparathyroidism, osteomalacia, and rickets) were identified. Any patients with osteoporosis or other systemic/endocrine disorders affecting bone quality were excluded. Traumatic, infectious, and neoplastic surgical indications were excluded. Cohorts were compared for demographics and 2-year outcome rates (medical/surgical complications and reoperations). Logistic regression was used to identify covariates associated with medical/surgical complications and revisions.
RESULT(S): A total of 28,959 patients were included (MBD, n=380 (1.33%); no-MBD, n=28,579). MBD pts were older (56.4 vs 53.1 years) and more often female (65.5% vs 49.80%) than no-MBD pts (all p<0.001). MBD pts had longer hospital stays (4.57 days vs 4.11 days, p=0.026), but charges were similar. MBD pts incurred higher rates of wound complications (11.8% vs 6.0%), acute renal failure (11.1% vs 4.7%), pneumonia (9.2% vs 4.4%), and implant related complications (12.1% vs 7.0%); all p<0.001. Rates of pseudarthrosis, PE, pulmonary complications, and UTI were similar between groups. MBDs were associated with developing both medical complications (OR=1.55) and surgical complications (OR=1.79), both p<0.001.
CONCLUSION(S): MBD patients have an increased risk of 2-year postop comps and reoperations following short lumbar fusion for DDD compared to patients without MBD when controlling for demographics and comorbidity profile. These data underscore the importance of preoperative screening and optimization in this patient population. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.
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BACKGROUND AND PURPOSE/OBJECTIVE:Coronavirus disease 2019 (COVID-19) evolved quickly into a global pandemic with myriad systemic complications, including stroke. We report the largest case series to date of cerebrovascular complications of COVID-19 and compare with stroke patients without infection. METHODS:Retrospective case series of COVID-19 patients with imaging-confirmed stroke, treated at 11 hospitals in New York, between March 14 and April 26, 2020. Demographic, clinical, laboratory, imaging, and outcome data were collected, and cases were compared with date-matched controls without COVID-19 from 1 year prior. RESULTS:<0.001), whereas COVID-19, older age, and intracranial hemorrhage independently predicted mortality. CONCLUSIONS:COVID-19 is an independent risk factor for stroke in hospitalized patients and mortality, and stroke presentations are frequently atypical.

Coronavirus disease 2019 (COVID-19) is a highly infectious pandemic caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It frequently presents with unremitting fever, hypoxemic respiratory failure, and systemic complications (e.g., gastrointestinal, renal, cardiac, and hepatic involvement), encephalopathy, and thrombotic events. The respiratory symptoms are similar to those accompanying other genetically related beta-coronaviruses (CoVs) such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East Respiratory Syndrome CoV (MERS-CoV). Hypoxemic respiratory symptoms can rapidly progress to Acute Respiratory Distress Syndrome (ARDS) and secondary hemophagocytic lymphohistiocytosis, leading to multi-organ system dysfunction syndrome. Severe cases are typically associated with aberrant and excessive inflammatory responses. These include significant systemic upregulation of cytokines, chemokines, and pro-inflammatory mediators, associated with increased acute-phase proteins (APPs) production such as hyperferritinemia and elevated C-reactive protein (CRP), as well as lymphocytopenia. The neurological complications of SARS-CoV-2 infection are high among those with severe and critical illnesses. This review highlights the central nervous system (CNS) complications associated with COVID-19 attributed to primary CNS involvement due to rare direct neuroinvasion and more commonly secondary CNS sequelae due to exuberant systemic innate-mediated hyper-inflammation. It also provides a theoretical integration of clinical and experimental data to elucidate the pathogenesis of these disorders. Specifically, how systemic hyper-inflammation provoked by maladaptive innate immunity may impair neurovascular endothelial function, disrupt BBB, activate CNS innate immune signaling pathways, and induce para-infectious autoimmunity, potentially contributing to the CNS complications associated with SARS-CoV-2 infection. Direct viral infection of the brain parenchyma causing encephalitis, possibly with concurrent neurovascular endotheliitis and CNS renin angiotensin system (RAS) dysregulation, is also reviewed.

BACKGROUND/UNASSIGNED:Dietary intervention in multiple sclerosis carries potential therapeutic implications. While studies utilizing animal models of multiple sclerosis (MS) have demonstrated intriguing findings, well-designed clinical trials are few in number. OBJECTIVE/UNASSIGNED:The objective of this study is to review the animal model and clinical literature regarding dietary factors in experimental autoimmune encephalitis (EAE) and MS. METHODS/UNASSIGNED:This manuscript provides a comprehensive review of current animal model and clinical knowledge related to dietary factors in MS. RESULTS/UNASSIGNED:While there is currently little data for any specific diet in MS, there is growing evidence that certain dietary factors may influence the disease. CONCLUSIONS/UNASSIGNED:Definitive information regarding dietary factors as a modifiable risk factor in MS will require larger randomized clinical trials.

Auto-reactive T cells are fundamental to many autoimmune processes, including neuromyelitis optica spectrum disorder (NMOSD). Several lines of evidence indicate that an antibody against aquaporin-4 (AQP4) is present in NMOSD patients. Further, this AQP4 antibody is pathogenic and can cause profound neurological damage. T cells are fundamental to many autoimmune processes, including NMOSD. Here we review work from animal models to discuss mechanisms by which auto-reactive T cells modulate the process by which antibodies cross the blood-brain barrier and orchestrate the local inflammatory milieu underlying NMOSD pathophysiology. We also examine clinical studies that document the presence of AQP4-specific T cells and the unique cytokine profile of NMOSD patients. This work encourages a renewed and broadened attention to the fundamental role of T cells in neuroautoimmune conditions which will hopefully lead to new therapies and better patients' outcomes.

There is increasing recognition in the neurological and psychiatric literature of patients with so-called isolated psychotic presentations (ie, with no, or minimal, neurological features) who have tested positive for neuronal autoantibodies (principally N-methyl-D-aspartate receptor antibodies) and who have responded to immunotherapies. Although these individuals are sometimes described as having atypical, mild, or attenuated forms of autoimmune encephalitis, some authors feel that that these cases are sufficiently different from typical autoimmune encephalitis to establish a new category of so-called autoimmune psychosis. We briefly review the background, discuss the existing evidence for a form of autoimmune psychosis, and propose a novel, conservative approach to the recognition of possible, probable, and definite autoimmune psychoses for use in psychiatric practice. We also outline the investigations required and the appropriate therapeutic approaches, both psychiatric and immunological, for probable and definite cases of autoimmune psychoses, and discuss the ethical issues posed by this challenging diagnostic category.