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Objective: To describe clinical and radiographic outcomes of surgical repair of cerebrospinal fluid-venous fistula (CVF), an increasingly recognized cause of spontaneous intracranial hypotension that is poorly responsive to epidural blood patch (EBP)., Methods: Retrospective review identified adult patients who had lateral decubitus digital subtraction myelography indicative of cerebrospinal fluid leak at Mayo Clinic between November 2018 and February 2020, with clearly localized CVF, followed by surgical treatment. Patients without available imaging before or after surgery were excluded. History of EBP and clinical response to EBP were evaluated along with surgical outcomes., Results: Of 25 patients with CVF who met protocol criteria and were included in the data analysis, 22 (88%) received EBP, but clinical benefit lasting ≥4 weeks occurred in only 2 of 22 (9%). Headache was the most prominent preoperative feature among patients (24/25; 96%). Following surgery, 18 of 24 (75%) patients had complete headache improvement, 4 (17%) had partial improvement, and 2 (8%) had no improvement. Ten of 25 (40%) patients reported cognitive disturbance at baseline; at follow-up, 5 of 10 (50%) had complete improvement, 3 (30%) had partial improvement, and 2 (20%) had no improvement. On postoperative brain magnetic resonance imaging, 6 of 25 (24%) patients had complete resolution of findings by Bern score criteria, 18 (72%) showed partial improvement, and 1 (4%) patient showed no improvement. Adverse events were minor and included surgical site pain and paresthesias., Conclusions: Surgical repair of CVF resulted in improvements in headache and other symptoms, with few side effects., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Pain flares are a common acute toxic effect after stereotactic body radiation therapy (SBRT) for spine metastasis. We aimed to identify a subset of patients with the highest rate of pain flare after spine SBRT to optimize prophylactic corticosteroid administration., Methods and Materials: The data set included 428 patients with 610 treatments. We defined pain flare as acute worsening of pain at the treatment site requiring new or higher dose therapy with corticosteroids, opiates, and/or hospitalization. Data were split into 70% training and 30% validation sets using a random number generator. After feature importance testing and generation of a correlation heatmap, feature extraction was performed via recursive partitioning analysis., Results: We identified 125 total pain flares (20%). Five variables met significance (P < .02) for model inclusion: renal primary, soft tissue involvement, Bilsky >0, spinal instability neoplastic score >6, and gross tumor volume >8 cc. One point was assigned for each variable. The low-risk group (score = 0, n = 159) had pain flare rates of 7.0% and 13.6% in the training and validation sets; the intermediate-risk group (score = 1, n = 150) had rates of 14.0% and 16.3%; and the high-risk group (score >1, n = 301) had rates of 28.8% and 31.3%. Patients in the high-risk group had higher rates of flare (odds ratio, 3.50; 95% confidence interval, 2.06-5.92) and accumulated health care costs 3 and 6 months post-SBRT, relative to intermediate- and low-risk patients (P < .001)., Conclusions: Our internally validated model identifies a high-risk group of patients more likely to develop a pain flare after spine SBRT, for whom prophylactic steroids may be considered. Evaluation in a clinical trial is warranted., (Copyright © 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: We analyzed the cost-effectiveness of standard palliative external beam radiation (EBRT, 8 Gy in 1 fraction), stereotactic body radiation therapy (SBRT, 24 Gy in 2 fractions), and radiofrequency ablation for painful spinal metastases. Single-fraction SBRT (delivering 24 Gy) was also assessed., Methods and Materials: A Markov state transition model was constructed. Key model parameters were derived from prospective clinical trial data. Strategies were compared using the incremental cost-effectiveness ratio (ICER), with effectiveness in quality-adjusted life-years (QALYs) and a willingness-to-pay threshold of $100,000 per QALY gained. Costs included both hospital and professional costs using 2020 Medicare reimbursement., Results: The base case demonstrated that 2-fraction SBRT was not cost-effective compared with single-fraction EBRT, with an ICER of $194,145 per QALY gained. Radiofrequency ablation was a more costly and less effective strategy in this model. Probabilistic sensitivity analysis demonstrated that EBRT was favored in 66% of model iterations. If median survival were improved after SBRT, 2-fraction SBRT became cost-effective, with ICERs of $80,394, $57,062, and $47,038 for 3-, 6-, and 9-month improvements in survival, respectively. Because 2-fraction SBRT data reported that 18% of patients had an indeterminant pain response at 3 months and 2-fraction SBRT is infrequently used in clinical practice, single-fraction SBRT data were also assessed. Single-fraction SBRT delivering 24 Gy was cost-effective compared with single-fraction EBRT, with an ICER of $92,833 per QALY gained., Conclusions: For appropriately chosen patients, single-fraction SBRT was more cost-effective than conventional EBRT or radiofrequency ablation. Conventional EBRT remains a cost-effective treatment for patients with poor expected survival., (Copyright © 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Vertebral cement augmentation techniques are routinely used to treat osteoporotic vertebral compression fractures (VCFs). In the current study, we used a state-level outpatient database to compare costs and postoperative outcomes between vertebroplasty and kyphoplasty., Methods: We queried the 2016 Florida State-Ambulatory Surgery Database of the Healthcare Cost and Utilization Project for patients undergoing thoracolumbar vertebroplasty or kyphoplasty for osteoporotic VCFs. Demographic and clinical characteristics, as well as postoperative outcomes were compared between the 2 groups., Results: A total of 105 patients (11.6%) who underwent vertebroplasty and 801 patients (88.4%) who underwent kyphoplasty were identified. Patients undergoing kyphoplasty were more likely to stay overnight or longer, with the P value trending toward significance (kyphoplasty with >1 day stay: 7.4% vs. vertebroplasty with >1 day stay: 1.9%; P = 0.086). Patients undergoing vertebroplasty had a significantly higher rate of discharge to home routine compared with patients undergoing kyphoplasty (97.1% [n = 102] vs. 94.1% [n = 754]; P < 0.001). Undergoing kyphoplasty was also associated with higher index admission costs ($40,706 vs. $18,965; P < 0.001) and higher readmission costs ($27,038 vs. $11,341; P = 0.046). The rates of 30-day and 90-day readmission were similar between the 2 groups (all P > 0.05). The rates of 30-day, 90-day, and overall readmission because of a new-onset fracture were also similar (all P > 0.05). However, vertebroplasty had a higher rate of readmissions associated with a procedure within a year (21.9% [n = 23] vs. 14.5% [n = 116]; P = 0.047)., Conclusions: Our analyses from a state-level database of patients undergoing vertebroplasty and kyphoplasty for osteoporotic VCFs show similar postoperative outcomes for the 2 procedures but a higher cost for kyphoplasty., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Klippel-Trenaunay syndrome (KTS) is associated with a wide variety of vascular and neurologic abnormalities, including venolymphatic malformations. A recent report postulated that patients with KTS may also be predisposed to spontaneous intracranial hypotension. We reviewed brain magnetic resonance imaging from 67 patients with KTS and unexpectedly noted findings of cerebrospinal fluid (CSF) hypotension in 4 of them., Case Description: Patients included a 39-year-old woman with episodic orthostatic headaches, a 62-year-old woman with orthostatic headaches and light-headedness, a 14-year-old girl with a history of headaches for years, and an asymptomatic 20-year-old man. All 4 patients had known KTS, and all had brain magnetic resonance imaging done during their evaluation showing evidence of CSF hypotension. The first 2 patients also had spine imaging demonstrating paraspinal and/or epidural venolymphatic malformations. The second patient had a meningeal diverticulum and underwent surgical repair with intraoperative evidence of a CSF leak., Conclusions: Patients with KTS have an increased incidence of CSF hypotension. While it is possible that intrinsic dural weakness may be responsible for this association, we hypothesize that these patients are also predisposed to developing CSF venous fistulas. Paraspinal and epidural venolymphatic malformations have been described in multiple patients with CSF venous fistulas. Such malformations were present in 2 of our 4 patients who underwent spine imaging. Patients with KTS with orthostatic headaches may benefit from brain and spine magnetic resonance imaging to assess for evidence of CSF hypotension and venolymphatic malformations. Decubitus digital subtraction myelography may also have a role in these patients if CSF venous fistulas are suspected., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Spontaneous cerebrospinal fluid (CSF) leaks can be an intractable cause of orthostatic headaches but have several treatable causes. CSF-venous fistulas are an increasingly recognized cause of rapid CSF leaks. Although CSF-venous fistulas have been previously reported in the literature, their imaging appearance, associated anomalies, and treatment are incompletely understood. We present a case of a CSF-venous fistula draining to adjacent venous malformations with symptoms responding to surgical treatment. This is the first such case to our knowledge showing enhancement of venous malformations on computed tomography myelography., Case Description: A 61-year-old woman with known soft tissue venous malformations presented with progressive hearing loss, headaches, and nausea. Brain magnetic resonance imaging performed at an outside institution showed findings of CSF hypotension. Her symptoms were refractory to a single-level blood patch. Digital subtraction and computed tomography myelography performed at our institution showed CSF-venous fistulas arising from thoracic nerve root sleeve diverticula and draining to paraspinal venous malformations. She was treated with surgical ligation of the fistula and associated nerve roots. At 3-month follow-up, she reported improvement in her headaches, and magnetic resonance imaging showed resolution of all brain abnormalities., Conclusions: CSF-venous fistulas are a relatively uncommon cause of spontaneous CSF leaks. Though difficult to diagnose, they can respond to surgical treatment as seen in this case. In our experience, decubitus digital subtraction myelography combined with computed tomography myelography is instrumental in making the diagnosis and fully characterizing any abnormalities associated with the fistula. This case also supports the suggested association between CSF-venous fistulas and venous malformations, which is worthy of continued study., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Human epidermis elaborates two small cationic, highly hydrophobic antimicrobial peptides (AMP), beta-defensin 2 (hBD2), and the carboxypeptide cleavage product of human cathelicidin (hCAP18), LL-37, which are co-packaged along with lipids within epidermal lamellar bodies (LBs) before their secretion. Because of their colocalization, we hypothesized that AMP and barrier lipid production could be coregulated by altered permeability barrier requirements. mRNA and immunostainable protein levels for mBD3 and cathelin-related antimicrobial peptide (CRAMP) (murine homologues of hBD2 and LL-37, respectively) increase 1-8 hours after acute permeability barrier disruption and normalize by 24 hours, kinetics that mirror the lipid metabolic response to permeability barrier disruption. Artificial permeability barrier restoration, which inhibits the lipid-synthetic response leading to barrier recovery, blocks the increase in AMP mRNA/protein expression, further evidence that AMP expression is linked to permeability barrier function. Conversely, LB-derived AMPs are also important for permeability barrier homeostasis. Despite an apparent increase in mBD3 protein, CRAMP-/- mice delayed permeability barrier recovery, attributable to defective LB contents and abnormalities in the structure of the lamellar membranes that regulate permeability barrier function. These studies demonstrate that (1) the permeability and antimicrobial barriers are coordinately regulated by permeability barrier requirements and (2) CRAMP is required for permeability barrier homeostasis.