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Although largely confined to the airways, SARS-CoV-2 infection has been associated with sensory abnormalities that manifest in both acute and chronic phenotypes. To gain insight on the molecular basis of these sensory abnormalities, we used the golden hamster model to characterize and compare the effects of infection with SARS-CoV-2 and influenza A virus (IAV) on the sensory nervous system. We detected SARS-CoV-2 transcripts but no infectious material in the cervical and thoracic spinal cord and dorsal root ganglia (DRGs) within the first 24 hours of intranasal virus infection. SARS-CoV-2–infected hamsters exhibited mechanical hypersensitivity that was milder but prolonged compared with that observed in IAV-infected hamsters. RNA sequencing analysis of thoracic DRGs 1 to 4 days after infection suggested perturbations in predominantly neuronal signaling in SARS-CoV-2–infected animals as opposed to type I interferon signaling in IAV-infected animals. Later, 31 days after infection, a neuropathic transcriptome emerged in thoracic DRGs from SARS-CoV-2–infected animals, which coincided with SARS-CoV-2–specific mechanical hypersensitivity. These data revealed potential targets for pain management, including the RNA binding protein ILF3, which was validated in murine pain models. This work elucidates transcriptomic signatures in the DRGs triggered by SARS-CoV-2 that may underlie both short- and long-term sensory abnormalities.

Despite being largely confined to the airways, SARS-CoV-2 infection has been associated with sensory abnormalities that manifest in both acute and long-lasting phenotypes. To gain insight on the molecular basis of these sensory abnormalities, we used the golden hamster infection model to characterize the effects of SARS-CoV-2 versus Influenza A virus (IAV) infection on the sensory nervous system. Efforts to detect the presence of virus in the cervical/thoracic spinal cord and dorsal root ganglia (DRGs) demonstrated detectable levels of SARS-CoV-2 by quantitative PCR and RNAscope uniquely within the first 24 hours of infection. SARS-CoV-2-infected hamsters demonstrated mechanical hypersensitivity during acute infection; intriguingly, this hypersensitivity was milder, but prolonged when compared to IAV-infected hamsters. RNA sequencing (RNA-seq) of thoracic DRGs from acute infection revealed predominantly neuron-biased signaling perturbations in SARS-CoV-2-infected animals as opposed to type I interferon signaling in tissue derived from IAV-infected animals. RNA-seq of 31dpi thoracic DRGs from SARS-CoV-2-infected animals highlighted a uniquely neuropathic transcriptomic landscape, which was consistent with substantial SARS-CoV-2-specific mechanical hypersensitivity at 28dpi. Ontology analysis of 1, 4, and 30dpi RNA-seq revealed novel targets for pain management, such as ILF3. Meta-analysis of all SARS-CoV-2 RNA-seq timepoints against preclinical pain model datasets highlighted both conserved and unique pro-nociceptive gene expression changes following infection. Overall, this work elucidates novel transcriptomic signatures triggered by SARS-CoV-2 that may underlie both short- and long-term sensory abnormalities while also highlighting several therapeutic targets for alleviation of infection-induced hypersensitivity.One Sentence SummarySARS-CoV-2 infection results in an interferon-associated transcriptional response in sensory tissues underlying time-dependent hypersensitivity.

Study Design: Retrospective cohort study. Objectives: Anterior cervical discectomy and fusion (ACDF) is commonly used to treat an array of cervical spine pathology and is associated with good outcomes and low complication rates. Diabetes mellitus (DM) is a common comorbidity for patients undergoing ACDF, but the literature is equivocal about the impact it has on outcomes. Because DM is a highly prevalent comorbidity, it is crucial to determine if it is an associated risk factor for outcomes after ACDF procedures. Methods: Patients at a single institution from 2008 to 2016 undergoing ACDF were compared on the basis of having a prior diagnosis of DM versus no DM. The 2 cohorts were compared utilizing univariate tests and multivariate logistic and linear regressions. Results: Data for 2470 patients was analyzed. Diabetic patients had significantly higher Elixhauser scores ( P < .0001). Univariate testing showed diabetic patients were more likely to suffer from sepsis (0.82% vs 0.10%, P = .03) and bleeding complications (3.0% vs 1.5%, P = .04). In multivariate analyses, diabetic patients had higher rates of non–home discharge (odds ratio [OR] = 1.37, 95% confidence interval [CI] = 1.07-1.75, P = .013) and prolonged length of stay (OR = 1.95, 95% CI = 1.25-3.05, P = .003), but similar complication (OR = 1.46, 95% CI = 0.85-2.52, P = .17), reoperation (OR = 0.77, 95% CI = 0.33-1.81, P = .55), and 90-day readmission (OR = 1.53, 95% CI = 0.97-2.43) rates compared to nondiabetic patients. Direct cost was also shown to be similar between the cohorts after adjusting for patient, surgical, and hospital-related factors (estimate = −$30.25, 95% CI = −$515.69 to $455.18, P = .90). Conclusions: Diabetic patients undergoing ACDF had similar complication, reoperation, and readmission rates, as well as similar cost of care compared to nondiabetic patients.

Study Design: Retrospective cohort study. Objective: The present study analyzes complication rates and episode-based costs for patients with and without diabetes mellitus (DM) following posterior lumbar fusion (PLF). Methods: PLF cases at a single institution from 2008 to 2016 were queried (n = 3226), and demographic and perioperative data were analyzed. Patients with and without the diagnosis of DM were compared using chi-square, Student’s t test, and multivariable regression modeling. Results: Patients with diabetes were older (63.10 vs 56.48 years, P < .001) and possessed a greater number of preoperative comorbidities (47.84% of patients had Elixhauser Comorbidity Index >0 vs 42.24%, P < .001) than did patients without diabetes. When controlling for preexisting differences, diabetes remained a significant risk factor for prolonged length of stay (OR = 1.59, 95% CI 1.26-2.01, P < .001), intensive care unit stay (OR = 1.52, 95% CI 1.07-2.17, P = .021), nonhome discharge (OR = 1.86, 95% CI 1.46-2.37, P < .001), 30-day readmission (OR = 2.15, 95% CI 1.28-3.60, P = .004), 90-day readmission (OR = 1.65, 95% CI 1.05-2.59, P = .031), 30-day emergency room visit (OR = 2.15, 95% CI 1.27-3.63, P = .004), and 90-day emergency room visit (OR = 2.27, 95% CI 1.41-3.65, P < .001). Cost modeling controlling for overall comorbidity burden demonstrated that diabetes was associated with a $1709 increase in PLF costs (CI $344-$3074, P = .014). Conclusions: The present findings indicate a correlation between diabetes and a multitude of postoperative adverse outcomes and increased costs, thus illustrating the substantial medical and financial burdens of diabetes for PLF patients. Future studies should explore preventive measures that may mitigate these downstream effects.

SUMMARYSARS-CoV-2 has been found capable of inducing prolonged pathologies collectively referred to as Long-COVID. To better understand this biology, we compared the short- and long-term systemic responses in the golden hamster following either SARS-CoV-2 or influenza A virus (IAV) infection. While SARS-CoV-2 exceeded IAV in its capacity to cause injury to the lung and kidney, the most significant changes were observed in the olfactory bulb (OB) and olfactory epithelium (OE) where inflammation was visible beyond one month post SARS-CoV-2 infection. Despite a lack of detectable virus, OB/OE demonstrated microglial and T cell activation, proinflammatory cytokine production, and interferon responses that correlated with behavioral changes. These findings could be corroborated through sequencing of individuals who recovered from COVID-19, as sustained inflammation in OB/OE tissue remained evident months beyond disease resolution. These data highlight a molecular mechanism for persistent COVID-19 symptomology and characterize a small animal model to develop future therapeutics.

The challenges of neurosurgical patient management and surgical decision-making during the 2019-2020 COVID-19 worldwide pandemic are immense and never-before-seen in our generation of neurosurgeons. In this case-based formatted report, we present the Mount Sinai Hospital (New York, NY) Department of Neurosurgery institutional experience in the epicenter of the pandemic and the guiding principles for our current management of intracranial, skull base, and spine tumors. The detailed explanations of our surgical reasoning for each tumor case is tailored to assist neurosurgeons across the United States as they face these complex operative decisions put forth by the realities of the pandemic.

SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has been found capable of inducing long term effects commonly referred to as post-acute sequelae of SARS-CoV-2 (PASC) or long COVID. To define the molecular basis of this condition, we compared the short- and long-term responses to influenza A virus and SARSCoV-2 in the golden hamster model. These data demonstrated that SARS-CoV-2 resulted in sustained changes to lung, kidney, and brain. The most significant change in response to SARS-CoV-2 was observed in the olfactory bulb, where persistent inflammation was visible beyond one month post infection. This was characterized by microglial activation, pro-inflammatory cytokine production, and a Type I interferon (IFN-I) response in the absence of detectable virus. Given the connection between olfactory bulb injury and neurological disorders, we postulate that this prolonged inflammation is an underlying cause of long COVID. Funding Information: This work was funded by generous support from the Marc Haas Foundation, the National Institutes of Health (NCI (R01CA234614) and NIAID (2R01AI107301) and NIDDK (R01DK121072 and 1RO3DK117252) to Department of Medicine, Weill Cornell Medicine (R.E.S.)), and DARPA’s PREPARE Program (HR0011-20-2-0040). The work was further funded by NINDS (NS111251, NSO86444, NSO86444S1)(V.Z., R.A.S.). Ethics Approval Statement: The Tissue Procurement Facility operates under Institutional Review Board (IRB) approved protocol and follows guidelines set by Health Insurance Portability and Accountability Act (HIPAA). Experiments using samples from human subjects were conducted in accordance with local regulations and with the approval of the IRB at the Weill Cornell Medicine. The autopsy samples are considered human tissue research and were collected under IRB protocols 20-04021814 and 19-11021069. All autopsies have consent for research use from next of kin, and these studies were determined as exempt by IRB at Weill Cornell Medicine under those protocol numbers.

We sought to compare the cost and in-hospital outcomes following lumbar microdiskectomy procedures by admission type.Patients undergoing lumbar microdiskectomy at a single institution from 2008 to 2016 following an elective admission (EL) were compared against those who were admitted from the emergency department (ED) or from elsewhere within or outside the hospital system (TR) for their perioperative outcomes and cost. Multivariable modeling controlled for age, sex, self-reported race, Elixhauser comorbidity score, payer type, number of segments, and procedure length.Of the 1249 patients included in this study, 1116 (89.4%) were admitted electively while 123 (9.8%) were admitted from the ED and 10 (0.8%) were transferred from other hospitals. EL patients had significantly lower comorbidity burdens (P0.0001). Univariate and multivariable analyses revealed that transfer admission patients experienced significantly longer hospitalizations (ED: +1.7 days; P0.0001; TR: +5.3 days; P0.0001) and higher direct costs (ED: $1889; P0.0001; TR: $7001; P0.0001) compared with EL patients. Despite these risks, ED and TR patients only had increased odds of nonhome discharge compared with EL patients (ED: 3.4; P = 0.002; TR: 7.9; P = 0.02).Patients admitted as transfers and from the ED had significantly increased hospitalization lengths of stay and direct costs compared with electively admitted patients.

Background /Objective: With a growing aging population in the United States, the number of operative lumbar spine pathologies continues to grow. Therefore, our objective was to estimate the future demand for lumbar spine surgery volumes for the United States to the year 2040. Methods The National/Nationwide Inpatient Sample was queried for years 2003-2015 for anterior interbody and posterior lumbar fusions (ALIF, PLF) to create national estimates of procedural volumes for those years. The average age and comorbidity burden was characterized, and Poisson modeling controlling for age and sex allowed for surgical volume prediction to 2040 in ten year increments. Age was grouped into categories ( 85), and estimates of surgical volumes for each age subgroup were created Results ALIF volume is expected to increase from 46,903 to 55,528, while PLF volume is expected to increase from 248,416 to 297,994 from 2020 to 2040. For ALIF, the largest increases are expected in the 45-54 year old (10,316 to 12,216) and 75-84 year old (2,898 to 5,340) age groups. Similarly the largest increases in PLF will be seen in the 65-74 year old (71,087 to 77,786) and 75-84 year old (28,253 to 52,062) age groups. Conclusion The large increases in expected volumes of ALIF and PLF could necessitate training of more spinal surgeons and an examination of projected costs. Further analyses are needed to characterize the needs of this increasingly large population of surgical patients.