Development of PainFace software to simplify, standardize, and scale up mouse grimace analyses.

ABSTRACT: Facial grimacing is used to quantify spontaneous pain in mice and other mammals, but scoring relies on humans with different levels of proficiency. Here, we developed a cloud-based software platform called PainFace ( http://painface.net ) that uses machine learning to detect 4 facial action units of the mouse grimace scale (orbitals, nose, ears, whiskers) and score facial grimaces of black-coated C57BL/6 male and female mice on a 0 to 8 scale. Platform accuracy was validated in 2 different laboratories, with 3 conditions that evoke grimacing-laparotomy surgery, bilateral hindpaw injection of carrageenan, and intraplantar injection of formalin. PainFace can generate up to 1 grimace score per second from a standard 30 frames/s video, making it possible to quantify facial grimacing over time, and operates at a speed that scales with computing power. By analyzing the frequency distribution of grimace scores, we found that mice spent 7x more time in a "high grimace" state following laparotomy surgery relative to sham surgery controls. Our study shows that PainFace reproducibly quantifies facial grimaces indicative of nonevoked spontaneous pain and enables laboratories to standardize and scale-up facial grimace analyses.

Development of PainFace software to simplify, standardize, and scale up mouse grimace analyses.

ABSTRACT: Facial grimacing is used to quantify spontaneous pain in mice and other mammals, but scoring relies on humans with different levels of proficiency. Here, we developed a cloud-based software platform called PainFace (http://painface.net) that uses machine learning to detect 4 facial action units of the mouse grimace scale (orbitals, nose, ears, whiskers) and score facial grimaces of black-coated C57BL/6 male and female mice on a 0 to 8 scale. Platform accuracy was validated in 2 different laboratories, with 3 conditions that evoke grimacing-laparotomy surgery, bilateral hindpaw injection of carrageenan, and intraplantar injection of formalin. PainFace can generate up to 1 grimace score per second from a standard 30 frames/s video, making it possible to quantify facial grimacing over time, and operates at a speed that scales with computing power. By analyzing the frequency distribution of grimace scores, we found that mice spent 7x more time in a "high grimace" state following laparotomy surgery relative to sham surgery controls. Our study shows that PainFace reproducibly quantifies facial grimaces indicative of nonevoked spontaneous pain and enables laboratories to standardize and scale-up facial grimace analyses.

Autism-linked UBE3A gain-of-function mutation causes interneuron and behavioral phenotypes when inherited maternally or paternally in mice.

The E3 ubiquitin ligase Ube3a is biallelically expressed in neural progenitors and glial cells, suggesting that UBE3A gain-of-function mutations might cause neurodevelopmental disorders irrespective of parent of origin. Here, we engineered a mouse line that harbors an autism-linked UBE3AT485A (T503A in mouse) gain-of-function mutation and evaluated phenotypes in animals that inherited the mutant allele paternally, maternally, or from both parents. We find that paternally and maternally expressed UBE3AT503A results in elevated UBE3A activity in neural progenitors and glial cells. Expression of UBE3AT503A from the maternal allele, but not the paternal one, leads to a persistent elevation of UBE3A activity in neurons. Mutant mice display behavioral phenotypes that differ by parent of origin. Expression of UBE3AT503A, irrespective of its parent of origin, promotes transient embryonic expansion of Zcchc12 lineage interneurons. Phenotypes of Ube3aT503A mice are distinct from Angelman syndrome model mice. Our study has clinical implications for a growing number of disease-linked UBE3A gain-of-function mutations.

Multi-omic profiling reveals the ataxia protein sacsin is required for integrin trafficking and synaptic organization.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a childhood-onset cerebellar ataxia caused by mutations in SACS, which encodes the protein sacsin. Cellular ARSACS phenotypes include mitochondrial dysfunction, intermediate filament disorganization, and progressive death of cerebellar Purkinje neurons. It is unclear why the loss of sacsin causes these deficits or why they manifest as cerebellar ataxia. Here, we perform multi-omic profiling in sacsin knockout (KO) cells and identify alterations in microtubule dynamics and mislocalization of focal adhesion (FA) proteins, including multiple integrins. Deficits in FA structure, signaling, and function can be rescued by targeting PTEN, a negative regulator of FA signaling. ARSACS mice possess mislocalization of ITGA1 in Purkinje neurons and synaptic disorganization in the deep cerebellar nucleus (DCN). The sacsin interactome reveals that sacsin regulates interactions between cytoskeletal and synaptic adhesion proteins. Our findings suggest that disrupted trafficking of synaptic adhesion proteins is a causal molecular deficit in ARSACS.

The weekend effect on mechanical thrombectomy: A nationwide analysis before and after the pivotal 2015 trials.

OBJECTIVES: As hospitals rapidly implement mechanical thrombectomy (MT) into stroke protocols following the pivotal trials in 2015, access to and outcomes from MT may be poorer for weekend-admitted patients. We sought to investigate whether a "weekend effect" influences MT outcomes nationally. MATERIALS AND METHODS: We identified stroke patients from 2010-2014 (pre-trials) to 2015-2017 (posttrials) using the Nationwide Readmissions Database. On multivariate analyses, we determined factors independently associated with receiving MT. Among MT patients, we then determined whether weekend admission was independently associated with inpatient mortality and unfavorable discharge. RESULTS: We identified 2,121,462 patients from 2010 to 2014, of whom 1.11% of weekday-admitted and 1.08% of weekend-admitted patients underwent MT. Of the 1,286,501 patients identified from 2015 to 2017, MT was performed in 2.82% and 2.91%, respectively. In the earlier cohort, weekend admission was independently associated with reduced odds of MT (odds ratio [OR] = 0.92, 95% confidence interval [CI]: 0.89-0.95, P < 0.0001), although this was not statistically significant in the later cohort. During both periods, age >80 years was independently associated with a reduced likelihood of receiving MT, and status as a teaching or large bed-size hospital was associated with a greater likelihood. Weekend admission was independently associated with unfavorable discharge only in the 2015-2017 cohort (OR = 1.11, 95% CI: 1.02-1.22, P = 0.02). CONCLUSIONS: While nationwide access to MT has improved for weekend-admitted patients, the elderly and those at smaller, nonteaching hospitals remain underserved. Although we found no effect of weekend admission on inpatient mortality, since the major shift in practice, an emerging "weekend effect" may influence discharge outcomes. Data suggest that some hospitals are being challenged to provide this new standard of care efficiently and equitably.

National Rates, Reasons, and Risk Factors for 30- and 90-Day Readmission and Reoperation Among Patients Undergoing Anterior Cervical Discectomy and Fusion: An Analysis Using the Nationwide Readmissions Database.

STUDY DESIGN: Retrospective cohort study of the Nationwide Readmissions Database (NRD). OBJECTIVE: To determine causes of and independent risk factors for 30- and 90-day readmission in a cohort of anterior cervical discectomy and fusion (ACDF) patients. SUMMARY OF BACKGROUND DATA: Identifying populations at high-risk of 30-day readmission is a priority in healthcare reform so as to reduce cost and patient morbidity. However, among patients undergoing ACDF, nationally-representative data have been limited, and have seldom described 90-day readmissions, early reoperation, or socioeconomic influences. METHODS: We queried the NRD, which longitudinally tracks 49.3% of hospitalizations, for all adult patients undergoing ACDF. We calculated the rates of, and determined reasons for, readmission and reoperation at 30 and 90 days, and determined risk factors for readmission at each timepoint. RESULTS: We identified 50,126 patients between January and September 2014. Of these, 2294 (4.6%) and 4152 (8.3%) were readmitted within 30 and 90 days of discharge, respectively, and were most commonly readmitted for infections, medical complications, and dysphagia. The characteristics most strongly associated with readmission were Medicare or Medicaid insurance, length of stay greater than or equal to 4 days, three or more comorbidities, and non-routine discharge, whereas surgical factors (e.g., greater number of vertebrae fused) were more modest. By 30 and 90 days, 8.2% and 11.7% of readmitted patients underwent an additional spinal procedure, respectively. CONCLUSION: Our analysis uses the NRD to thoroughly characterize readmission in the general ACDF population. Readmissions are often delayed (after 30 days), strongly associated with insurance status, and many result in reoperation. Our results are crucial for risk-stratifying future ACDF patients and developing interventions to reduce readmission.Level of Evidence: 3.

Spinal macrophages resolve nociceptive hypersensitivity after peripheral injury.

Peripheral nerve injury induces long-term pro-inflammatory responses in spinal cord glial cells that facilitate neuropathic pain, but the identity of endogenous cells that resolve spinal inflammation has not been determined. Guided by single-cell RNA sequencing (scRNA-seq), we found that MRC1+ spinal cord macrophages proliferated and upregulated the anti-inflammatory mediator Cd163 in mice following superficial injury (SI; nerve intact), but this response was blunted in nerve-injured animals. Depleting spinal macrophages in SI animals promoted microgliosis and caused mechanical hypersensitivity to persist. Conversely, expressing Cd163 in spinal macrophages increased Interleukin 10 expression, attenuated micro- and astrogliosis, and enduringly alleviated mechanical and thermal hypersensitivity in nerve-injured animals. Our data indicate that MRC1+ spinal macrophages actively restrain glia to limit neuroinflammation and resolve mechanical pain following a superficial injury. Moreover, we show that spinal macrophages from nerve-injured animals mount a dampened anti-inflammatory response but can be therapeutically coaxed to promote long-lasting recovery of neuropathic pain.

"Enticing" but Not Necessarily a "Space Designed for Me": Experiences of Urban Park Use by Older Adults with Disability.

Urban parks are spaces that can enhance older adults' physical, social and psychological wellbeing. As the prevalence of older adults with disability increases, it is important that urban parks are accessible to this population so that they too might gain health benefits. There is limited literature investigating the experiences of urban parks by older adults with disability. This qualitative study, set in a region of New Zealand, explored the experiences, including accessibility, of urban parks by 17 older adults (55 years and older) with self-reported disabilities. Three focus groups (n = 4, 5 and 4 people) and four individual interviews were undertaken. Data were analyzed using the General Inductive Approach. Two primary themes of "Enticing" and "Park use considerations" are presented. Urban parks and green spaces are perceived to provide an environment for older adults with a disability to improve their physical, psychosocial and spiritual health, and social connectedness. Parks that are not age, ability or culture diverse are uninviting and exclusive. Meaningful collaboration between park designers, city councils and people with disability is required to maximize the public health benefits of parks and make parks inviting and accessible for users of all ages, cultures and abilities. Park co-design with people with disability may provide one means of improving accessibility and park usability and thus park participation by older adults with disability.

Deletion of Topoisomerase 1 in excitatory neurons causes genomic instability and early onset neurodegeneration.

Topoisomerase 1 (TOP1) relieves torsional stress in DNA during transcription and facilitates the expression of long (>100 kb) genes, many of which are important for neuronal functions. To evaluate how loss of Top1 affected neurons in vivo, we conditionally deleted (cKO) Top1 in postmitotic excitatory neurons in the mouse cerebral cortex and hippocampus. Top1 cKO neurons develop properly, but then show biased transcriptional downregulation of long genes, signs of DNA damage, neuroinflammation, increased poly(ADP-ribose) polymerase-1 (PARP1) activity, single-cell somatic mutations, and ultimately degeneration. Supplementation of nicotinamide adenine dinucleotide (NAD+) with nicotinamide riboside partially blocked neurodegeneration, and increased the lifespan of Top1 cKO mice by 30%. A reduction of p53 also partially rescued cortical neuron loss. While neurodegeneration was partially rescued, behavioral decline was not prevented. These data indicate that reducing neuronal loss is not sufficient to limit behavioral decline when TOP1 function is disrupted.

Ethical and medicolegal aspects in the management of neurosurgical emergencies among Jehovah's Witnesses: Clinical implications and review.

When an incapacitated Jehovah's Witness neurologically deteriorates and requires immediate craniectomy, institutional protocols may delay surgery if the patient's refusal of blood products is ambiguous. We are among the first to describe such an ethically contentious case in emergency neurosurgery, review the morbidity of operative delays, discuss medicolegal concerns raised, and provide a detailed guide to hemostasis in patients who refuse blood products. We discuss the case of a 46-year-old woman presented with nausea, vomiting, and right-sided weakness, progressing to stupor over several hours. When an initial Computed Tomography (CT) scan showed a large, left-sided intraparenchymal hematoma with significant midline shift, she was booked for an emergency hemicraniectomy. According to the family, she was a Jehovah's Witness and would have refused blood consent, but was without the proper documentation. Despite her worsening neurological status, an indeterminate blood consent delayed surgery for more than two hours. Her neurological exam did not improve postoperatively, and she later expired. The ethical, legal, and operative concerns that arise in the emergency neurosurgical treatment of Jehovah's Witness patients pose unique management challenges. Since operative delay is a preventable cause of mortality in patients requiring urgent craniectomy, and the likelihood of requiring a transfusion from hemorrhage is minimal, an ambiguous blood consent should not postpone a potentially life-saving treatment. For the beneficence and autonomy of Jehovah's Witness patients, institutional policies should respect the family's wishes in order to expedite surgical decompression. In addition to discussing the nuances of such ethical considerations, we also provide a detailed list of commonly used, topical and parenteral hemostatic agents from the neurosurgical operating room which, depending on whether they are blood-derived, either should or should not be used when treating a Jehovah's Witness.

Microsurgical Clip Ligation of an Unruptured Azygos Bifurcation Aneurysm Indented by the Falx Cerebri: 3-Dimensional Operative Video.

Dissecting pericallosal aneurysms from the falx cerebri is technically challenging, as one must release the adherent dome but minimize shearing injury, which could result in intraoperative rupture. We discuss a 51-yr-old woman with a history of hypertension and smoking who presented with severe headaches and was found to have a 6-mm unruptured, multilobulated pericallosal aneurysm abutting the falx, with anterior and superior projecting domes on either side. She also had an azygos anterior cerebral artery (ACA), a rare anatomic variant associated with pericallosal aneurysms, where both A1 segments form a single A2. After considering endovascular and open surgical techniques, we proceeded with clip ligation given her younger age, smoking history, daughter aneurysms seen on angiography, and azygos ACA. We positioned her supine with her head turned lateral, left side down to maximize gravitational retraction, mapped a bicoronal incision, and performed a small craniotomy, followed by an interhemispheric approach. Rather than cutting the falx around the dome, a described technique that risks blind vessel injury, we temporarily clipped inflow vessels to reduce the dome's turgor and sharply and bluntly dissected apart its attachments, which freed the aneurysm from beneath the falx and allowed visualization of associated vessels. Using suction to manipulate the dome, we then placed stacked, angled clips, and used a micro-Doppler to confirm brisk inflow and outflow. Postoperatively, she was neurologically intact, and her angiogram showed no residual aneurysm. Our 3-dimensional video demonstrates a safer, alternative approach to treating this rare aneurysm with its associated anatomical variant. Patient consented to her clinical presentation and microscope media being used for academic purposes.

Outcomes and Spectrum of Major Neurovascular Events Among COVID-19 Patients: A 3-Center Experience.

BACKGROUND: Preliminary data suggest that Coronavirus Disease-2019 (COVID-19) is associated with hypercoagulability and neurovascular events, but data on outcomes is limited. OBJECTIVE: To report the clinical course and outcomes of a case series of COVID-19 patients with a variety of cerebrovascular events. METHODS: We performed a multicentric, retrospective chart review at our three academic tertiary care hospitals, and identified all COVID-19 patients with cerebrovascular events requiring neuro-intensive care and/or neurosurgical consultation. RESULTS: We identified 26 patients between March 1 and May 24, 2020, of whom 12 (46%) died. The most common event was a large-vessel occlusion (LVO) in 15 patients (58%), among whom 8 died (8/15, 53%). A total of 9 LVO patients underwent mechanical thrombectomy, of whom 5 died (5/9, 56%). A total of 7 patients (27%) presented with intracranial hemorrhage. Of the remaining patients, 2 had small-vessel occlusions, 1 had cerebral venous sinus thrombosis, and another had a vertebral artery dissection. Acute Respiratory Distress Syndrome occurred in 8 patients, of whom 7 died. Mortalities had a higher D-dimer on admission (mean 20 963 ng/mL) than survivors (mean 3172 ng/mL). Admission Glasgow Coma Scale (GCS) score was poor among mortalities (median 7), whereas survivors had a favorable GCS at presentation (median 14) and at discharge (median 14). CONCLUSION: COVID-19 may be associated with hemorrhage as well as ischemia, and prognosis appears poorer than expected-particularly among LVO cases, where outcome remained poor despite mechanical thrombectomy. However, a favorable neurological condition on admission and lower D-dimer may indicate a better outcome.

Enhanced histamine-induced itch in diacylglycerol kinase iota knockout mice.

Subsets of small-diameter dorsal root ganglia (DRG) neurons detect pruritogenic (itch-causing) and algogenic (pain-causing) stimuli and can be activated or sensitized by chemical mediators. Many of these chemical mediators activate receptors that are coupled to lipid hydrolysis and diacylglycerol (DAG) production. Diacylglycerol kinase iota (DGKI) can phosphorylate DAG and is expressed at high levels in small-diameter mouse DRG neurons. Given the importance of these neurons in sensing pruritogenic and algogenic chemicals, we sought to determine if loss of DGKI impaired responses to itch- or pain-producing stimuli. Using male and female Dgki-knockout mice, we found that in vivo sensitivity to histamine-but not other pruritogens-was enhanced. In contrast, baseline pain sensitivity and pain sensitization following inflammatory or neuropathic injury were equivalent between wild type and Dgki-/- mice. In vitro calcium responses in DRG neurons to histamine was enhanced, while responses to algogenic ligands were unaffected by Dgki deletion. These data suggest Dgki regulates sensory neuron and behavioral responses to histamine, without affecting responses to other pruritogenic or algogenic agents.

Return to the Emergency Room with or without Readmission After Endoscopic Transsphenoidal Surgery in Socioeconomically Disadvantaged Patients at an Urban Medical Center.

BACKGROUND: Although reducing 30-day hospital readmissions is now a priority in neurosurgical quality improvement, postoperative emergency room (ER) visits have remained poorly understood, in particular, in populations with limited access to outpatient care. After endoscopic transsphenoidal surgery, the unique pathologic entities treated can engender a variety of surgical and metabolic complications-often dangerous, delayed, and nonspecific in presentation. We sought to characterize the causes and timing of ER visits-with or without readmission-in a socioeconomically disadvantaged population. METHODS: We reviewed all the patients undergoing ETS by our skull base team from 2009 to 2017 to determine their socioeconomic profile and causes of ER visits. For external validation, we compared our results with national data from the American College of Surgeons National Surgical Quality Improvement Program. RESULTS: Of the 229 patients, 35 (15.3%) had visited the ER within 30 days of discharge. Of these 229 patients, 21 (9.2%) were readmitted, and 109 (47.6%) were insured by Medicaid. The most common reasons for the ER visits were headache (8 of 35 [22.9%]), hyponatremia (7 of 35 [20.0%]), and epistaxis (5 of 35 [14.3%]). The most common cause for readmission was symptomatic hyponatremia (6 of 21 [28.6%]). The other reasons for readmission included meningitis (2 of 21 [9.5%]), adrenal crisis (2 of 21 [9.5%]), and cerebrospinal fluid leakage (1 of 21 [4.8%]). The average time to readmission was 10.9 days. According to the National Surgical Quality Improvement Program database, the 30-day readmission rate was 5.5%, of which 22.2% were for hyponatremia. CONCLUSION: Delayed hyponatremia accounts for a large proportion of ER visits and unplanned readmissions. Close follow-up with diligent, multidisciplinary care might reduce the number of ER visits and readmission in this population.

Topical vancomycin to reduce surgical-site infections in neurosurgery: Study protocol for a multi-center, randomized controlled trial.

Surgical-site infections (SSIs) account for 20% of all healthcare-associated infections, are the most common nosocomial infection among surgical patients, and are a focus of quality improvement initiatives. Despite implementation of many quality care measures (e.g. prophylactic antibiotics), SSIs remain a significant cause of morbidity, mortality, and economic burden, particularly in the field of neurosurgery. Topical vancomycin is increasingly utilized in instrumented spinal and cardiothoracic procedures, where it has been shown to reduce the risk of SSIs. However, a randomized controlled trial assessing its efficacy in the general neurosurgical population has yet to be done. The principle aim of "Topical Vancomycin for Neurosurgery Wound Prophylaxis" (NCT02284126) is to determine whether prophylactic, topical vancomycin reduces the risk of SSIs in the adult neurosurgical population. This prospective, multicenter, patient-blinded, randomized controlled trial will enroll patients to receive the standard of care plus topical vancomycin, or the standard of care alone. The primary endpoint of this study is a SSI by postoperative day (POD) 30. Patients must be over 18years of age. Patients are excluded for renal insufficiency, vancomycin allergy, and some ineligible procedures. Univariate analysis and logistic regression will determine the effect of topical vancomycin on SSIs at 30days. A randomized controlled trial is needed to determine the efficacy of this treatment. Results of this trial are expected to directly influence the standard of care and prevention of SSIs in neurosurgical patients.

Enhanced Nociception in Angelman Syndrome Model Mice.

Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by mutation or deletion of the maternal UBE3A allele. The maternal UBE3A allele is expressed in nearly all neurons of the brain and spinal cord, whereas the paternal UBE3A allele is repressed by an extremely long antisense transcript (UBE3A-ATS). Little is known about expression of UBE3A in the peripheral nervous system, where loss of maternal UBE3A might contribute to AS phenotypes. Here we sought to examine maternal and paternal Ube3a expression in DRGs neurons and to evaluate whether nociceptive responses were affected in AS model mice (global deletion of maternal Ube3a allele; Ube3am-/p+). We found that most large-diameter proprioceptive and mechanosensitive DRG neurons expressed maternal Ube3a and paternal Ube3a-ATS In contrast, most small-diameter neurons expressed Ube3a biallelically and had low to undetectable levels of Ube3a-ATS Analysis of single-cell DRG transcriptomes further suggested that Ube3a is expressed monoallelically in myelinated large-diameter neurons and biallelically in unmyelinated small-diameter neurons. Behavioral responses to some noxious thermal and mechanical stimuli were enhanced in male and female AS model mice; however, nociceptive responses were not altered by the conditional deletion of maternal Ube3a in the DRG. These data suggest that the enhanced nociceptive responses in AS model mice are due to loss of maternal Ube3a in the central, but not peripheral, nervous system. Our study provides new insights into sensory processing deficits associated with AS.SIGNIFICANCE STATEMENT Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss or mutation of the maternal UBE3A allele. While sensory processing deficits are frequently associated with AS, it is currently unknown whether Ube3a is expressed in peripheral sensory neurons or whether maternal deletion of Ube3a affects somatosensory responses. Here, we found that Ube3a is primarily expressed from the maternally inherited allele in myelinated large-diameter sensory neurons and biallelically expressed in unmyelinated small-diameter neurons. Nociceptive responses to select noxious thermal and mechanical stimuli were enhanced following global, but not sensory neuron-specific, deletion of maternal Ube3a in mice. These data suggest that maternal loss of Ube3a affects nociception via a central, but not peripheral mechanism, with implications for AS.

Association of Steroid Use with Deep Venous Thrombosis and Pulmonary Embolism in Neurosurgical Patients: A National Database Analysis.

OBJECTIVE: Venous thromboembolism (VTE) is a major preventable cause of morbidity and mortality in hospitalized patients and is a widely accepted measure for quality of care. Prolonged corticosteroid therapy, which is common in neurosurgical patients, has been associated with VTE. Using a national database, we sought to determine whether corticosteroid use for >10 days was an independent risk factor for deep venous thrombosis (DVT) and pulmonary embolism (PE). METHODS: The well-validated American College of Surgeons National Surgical Quality Improvement Program database was queried to evaluate the rates of VTE during the period 2006-2013 in patients undergoing neurosurgical procedures. A multivariate regression model was constructed to assess the effect of prolonged corticosteroid use on the occurrence of PE and DVT by postoperative day 30. RESULTS: Of 94,620 patients identified, 565 (0.60%) developed PE and 1057 (1.12%) developed DVT within 30 days after surgery. In the multivariate model, patients receiving corticosteroids were significantly more likely to have PE (odds ratio = 1.47, 95% confidence interval = 1.13-1.90, P = 0.004) and DVT (odds ratio = 1.55, 95% confidence interval = 1.28-1.87, P < 0.001). Other factors independently associated with development of PE and DVT included the presence of malignancy, longer hospitalization, certain infections (including pneumonia and urinary tract infections), and stroke with a neurologic deficit. CONCLUSIONS: In the neurosurgical population, prolonged courses of corticosteroids are associated with an increased risk of developing postoperative DVT and PE, even when controlling for potential confounders.

Preoperative chemotherapy and corticosteroids: independent predictors of cranial surgical-site infections.

OBJECT Preoperative corticosteroids and chemotherapy are frequently prescribed for patients undergoing cranial neurosurgery but may pose a risk of postoperative infection. Postoperative surgical-site infections (SSIs) have significant morbidity and mortality, dramatically increase the length and cost of hospitalization, and are a major cause of 30-day readmission. In patients undergoing cranial neurosurgery, there is a lack of data on the role of patient-specific risk factors in the development of SSIs. The authors of this study sought to determine whether chemotherapy and prolonged steroid use before surgery increase the risk of an SSI at postoperative Day 30. METHODS Using the national prospectively collected American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database for 2006-2012, the authors calculated the rates of superficial, deep-incisional, and organ-space SSIs at postoperative Day 30 for neurosurgery patients who had undergone chemotherapy or had significant steroid use within 30 days before undergoing cranial surgery. Trauma patients, patients younger than 18 years, and patients with a preoperative infection were excluded. Univariate analysis was performed for 25 variables considered risk factors for superficial and organ-space SSIs. To identify independent predictors of SSIs, the authors then conducted a multivariate analysis in which they controlled for duration of operation, wound class, white blood cell count, and other potential confounders that were significant on the univariate analysis. RESULTS A total of 8215 patients who had undergone cranial surgery were identified. There were 158 SSIs at 30 days (frequency 1.92%), of which 52 were superficial, 27 were deep-incisional, and 79 were organ-space infections. Preoperative chemotherapy was an independent predictor of organ-space SSIs in the multivariate model (OR 5.20, 95% CI 2.33-11.62, p < 0.0001), as was corticosteroid use (OR 1.86, 95% CI 1.03-3.37, p = 0.04), but neither was a predictor of superficial or deep-incisional SSIs. Other independent predictors of organ-space SSIs were longer duration of operation (OR 1.16), wound class of ≥ 2 (clean-contaminated and further contaminated) (OR 3.17), and morbid obesity (body mass index ≥ 40 kg/m(2)) (OR 3.05). Among superficial SSIs, wound class of 3 (contaminated) (OR 6.89), operative duration (OR 1.13), and infratentorial surgical approach (OR 2.20) were predictors. CONCLUSIONS Preoperative chemotherapy and corticosteroid use are independent predictors of organ-space SSIs, even when data are controlled for leukopenia. This indicates that the disease process in organ-space SSIs may differ from that in superficial SSIs. In effect, this study provides one of the largest analyses of risk factors for SSIs after cranial surgery. The results suggest that, in certain circumstances, modulation of preoperative chemotherapy or steroid regimens may reduce the risk of organ-space SSIs and should be considered in the preoperative care of this population. Future studies are needed to determine optimal timing and dosing of these medications.

Causes and Timing of Unplanned Early Readmission After Neurosurgery.

BACKGROUND: Reducing the rate of 30-day hospital readmission has become a priority in healthcare quality improvement policy, with a focus on better characterizing the reasons for unplanned readmission. In neurosurgery, however, peer-reviewed analyses describing the patterns of readmission have been limited in their number and generalizability. OBJECTIVE: To determine the incidence, timing, and causes of 30-day readmission after neurosurgical procedures. METHODS: We conducted a retrospective longitudinal study from 2009 to 2012 using the Statewide Planning And Research Cooperative System, which collects patient-level details for all admissions and discharges within New York. We identified patients readmitted within 30 days of initial discharge. The rate of, reasons for, and time to readmission were determined overall and within 4 subgroups: craniotomies, cranial surgery without craniotomy, spine, and neuroendovascular procedures. RESULTS: There were 163 743 index admissions, of whom 14 791 (9.03%) were readmitted. The most common reasons for unplanned readmission were infection (29.52%) and medical complications (19.22%). Median time to readmission was 11 days, with hemorrhagic strokes and seizures occurring earlier, and medical complications and infections occurring later. Readmission rates were highest among patients undergoing cerebrospinal fluid shunt revision and malignant tumor resection (15.57%-22.60%). Spinal decompressions, however, accounted for the largest volume of readmissions (33.13%). CONCLUSION: Many readmissions may be preventable and occur at predictable time intervals. The causes and timing of readmission vary significantly across neurosurgical subgroups. Future studies should focus on detecting specific complications in select cohorts at predefined time points, which may allow for interventions to lower costs and reduce patient morbidity. ABBREVIATIONS: CSF, cerebrospinal fluidIQR, interquartile rangeSPARCS, Statewide Planning And Research Cooperative System.