Urinary 15-F2t-Isoprostane Concentrations in Dogs with Liver Disease.

Isoprostanes are stable end products of lipid peroxidation that can be used as markers of oxidative stress. It was previously reported that a cohort of dogs with various liver diseases had increased urinary isoprostane concentrations compared to healthy control (HC) dogs. The aim of this study was to measure and report urinary isoprostane concentrations in dogs with different types of liver diseases. Urine was collected from 21 HC dogs and from 40 dogs with liver disease, including 25 with chronic hepatitis (CH), 7 with steroid hepatopathy (SH), and 8 with a congenital portosystemic shunt (CPSS). In this prospective, observational study, urinary 15-F2t-isoprostane (F2-IsoP) concentrations were measured by liquid chromatography/mass spectrometry and normalized to urinary creatinine concentrations. Concentrations were compared between groups using a Kruskal-Wallis test followed by Dunn's multiple comparisons tests. Significance was set at p < 0.05. The median (range) urinary F2-IsoP to creatinine ratios (ng/mg UCr) were 3.6 (2.2-12.4) for HC dogs, 5.7 (2.4-11.3) for dogs with CH, 4.8 (2.4-8.6) for dogs with SH, and 12.5 (2.9-22.9) for dogs with CPSS. CPSS dogs had significantly higher urinary F2-IsoP concentrations than HC dogs (p = 0.004), suggesting increased oxidative stress among this cohort.

Major complications of dural venous sinus stenting for idiopathic intracranial hypertension: case series and management considerations.

BACKGROUND: Venous sinus stenting (VSS) is a safe, effective, and increasingly popular treatment option for selected patients with idiopathic intracranial hypertension (IIH). Serious complications associated with VSS are rarely reported. METHODS: Serious complications after VSS were identified retrospectively from multicenter databases. The cases are presented and management strategies are discussed. RESULTS: Six major acute and chronic complications after VSS were selected from a total of 811 VSS procedures and 1466 venograms for IIH. These included an acute subdural hematoma from venous extravasation, cases of both intraprocedural and delayed stent thrombosis, an ultimately fatal cerebellar hemorrhage resulting in acute obstructive hydrocephalus, venous microcatheter perforation during venography and manometry, and a patient who developed subarachnoid hemorrhage and subdural hematoma after cerebellar cortical vein perforation. The six cases are reviewed and learning points regarding complication avoidance and management are presented. CONCLUSION: We report on six rare, major complications after VSS for IIH. Familiarity with these potential complications and appropriate timely management may allow for good clinical outcomes.

Therapeutic Targeting of Retinal Immune Microenvironment With CSF-1 Receptor Antibody Promotes Visual Function Recovery After Ischemic Optic Neuropathy.

Retinal ischemia/reperfusion injury (RI) is a common cause of irreversible visual impairment and blindness in elderly and critical unmet medical need. While no effective treatment is available for RI, microglial activation and local immune responses in the retina are thought to play important roles in the pathophysiology of neurodegeneration. While survival and activation of microglia depend critically on colony-stimulating factor receptor (CSF-1R) signaling, it remains unclear if targeting the retinal immune microenvironments by CSF-1RAb after RI is sufficient to rescue vision and present a potentially effective therapy. Here we used rodent models of RI and showed that retinal ischemia induced by acute elevation of intraocular pressure triggered an early activation of microglia and macrophages in the retina within 12 h. This was followed by lymphocyte infiltration and increased production of pro-inflammatory cytokines. Intravitreal injection of CSF-1R neutralizing antibody (CSF-1RAb) after RI significantly blocked microglial activation and the subsequent T cell recruitment. This also led to improved retinal ganglion cell survival and function measured by cell quantification and electroretinogram positive scotopic threshold responses, as well as increased visual acuity and contrast sensitivity as assessed by optomotor reflex-based assays, when compared to the isotype-treated control group. Moreover, the administration of CSF-1RAb efficiently attenuated inflammatory responses and activation of human microglia in culture, suggesting a therapeutic target with human relevance. These results, together with the existing clinical safety profiles, support that CSF-1RAb may present a promising therapeutic avenue for RI, a currently untreatable condition, by targeting microglia and the immune microenvironment in the retina to facilitate neural survival and visual function recovery.

Endovascular management of acute postprocedural flow diverting stent thrombosis.

INTRODUCTION: Postprocedural thrombosis is a rare complication after flow diverting stent (FD) implantation for aneurysm treatment with few reported cases in the literature. Management strategies and outcomes associated with this complication have not been reported. METHODS: A multicenter retrospective series of cases of acute postprocedural FD thrombosis were compiled and prevalence was calculated based on procedural volumes over a 7 year period. Acute postprocedural FD thrombosis was defined as the development of neurologic deficit with angiographic imaging demonstrating acute thrombus within the index FD stent at least 2 hours following completion of the implantation procedure. RESULTS: A total of 10 cases of postprocedural thrombosis were identified at five participating centers among a total of 768 patients treated (prevalence 1.3%). Thrombosis occurred a median of 5.5 days after implantation (range 0-83 days). 9/10 patients underwent emergent angiography with intent to perform endovascular reperfusion. A variety of different endovascular treatments were used, including aspiration thrombectomy, retrievable stent thrombectomy, balloon angioplasty, and intra-arterial thrombolytic infusion, without any procedural complications. There were no instances of FD migration, stent kinking, or aneurysm rupture. 90% of patients achieved Thrombolysis in Cerebral Infarction 2B or greater revascularization. Favorable clinical outcomes (modified Rankin Scale score of 0-2) at 3 months were achieved in 88% of patients. CONCLUSION: Acute postprocedural thrombosis of an FD is a rare complication that occurs in approximately 1-2% of patients after aneurysm treatment. Patients presenting with acute postprocedural FD thrombosis should be aggressively managed using large vessel occlusion thrombectomy techniques, as good angiographic and clinical outcomes are possible.

Preliminary evaluation of fecal fatty acid concentrations in cats with chronic kidney disease and correlation with indoxyl sulfate and p-cresol sulfate.

BACKGROUND: Straight- and branched-chain (BCFA) short-chain fatty acids (SCFAs) are produced by colonic microbiota and have both beneficial and deleterious effects in humans with chronic kidney disease (CKD). Fecal SCFAs in cats with CKD have not been described. OBJECTIVE: To characterize fecal SCFA concentrations in cats with CKD as compared to healthy geriatric cats and correlate SCFA to serum indoxyl sulfate (IS) and p-cresol sulfate (pCS) concentrations. ANIMALS: Twenty-eight cats with CKD (International Renal Interest Society [IRIS] stages 2, 3, and 4) and 11 older (≥ 8 years) healthy geriatric cats. METHODS: Prospective, cross-sectional study. Voided feces were analyzed using stable isotope dilution gas chromatography-mass spectrometry to determine fecal concentrations of SCFAs. Serum concentrations of IS and pCS were measured using liquid chromatography tandem mass spectrometry. RESULTS: Fecal isovaleric acid concentrations were significantly higher in CKD cats(P = .02) Cats with IRIS CKD stage 3 and 4 had significantly higher fecal isovaleric acid concentrations compared to healthy geriatric cats (P = .03), but not compared to IRIS CKD stage 2 cats. Total fecal concentrations of BCFAs were found to correlate weakly with serum creatinine concentration (rho, 0.33; P = .05), blood urea nitrogen concentration (rho, 0.40; P = .01), and pCS concentration (rho, 0.35; P = .04). CONCLUSIONS AND CLINICAL IMPORTANCE: Fecal isovaleric acid concentrations were higher in CKD cats, particularly in late stage disease, compared to healthy geriatric cats. Fecal BCFA concentrations correlated with pCS and were higher in cats with muscle wasting, providing evidence for malassimilation of protein in CKD cats.

Effect of Penalty Minute Rule Change on Injuries and Game Disqualification Penalties in High School Ice Hockey.

BACKGROUND: Recent efforts have focused on eliminating dangerous hits in ice hockey. Fair play rule changes have successfully reduced injury risk but have not been widely implemented. PURPOSE: To determine the effect of a penalty infraction minutes (PIM) rule change in high school boys' ice hockey on injuries and game disqualification penalties. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Injury data were collected from 2 Rhode Island hospital systems and game/penalty data through the Rhode Island Hockey Coaches Association website. Participants included high school boys' hockey varsity players aged 13 to 19 years presenting to 5 emergency departments for hockey injuries during 6 seasons (December 2012-April 2018). Rule change for the 2015-2016 season implemented varying suspensions for players accumulating ≥50 PIM and ≥70 PIM during regular season and playoffs. Injuries were classified as body checking or non-body checking related, and injury rates pre- versus post-rule change were compared via the Cochran-Mantel-Haenszel chi-square test with the odds ratio (OR) to measure risk reduction. RESULTS: During the study period, 1762 boys' high school varsity hockey games were played. Of 134 game-related injuries, 82 (61.2%) were attributable to body checking. The PIM rule change was associated with a significant reduction in all injuries (OR, 0.55; 95% CI, 0.35-0.86; P = .008), concussion/closed head injury (OR, 0.44; 95% CI, 0.23-0.85; P = .012), and combined subgroups of concussion/closed head injury and upper body injury (OR, 0.50; 95% CI, 0.31-0.80; P = .003). Game disqualification penalties per season were not significantly reduced following the rule change, occurring in 5.2% of games before the rule change and 4.4% of games after (OR, 0.84; 95% CI, 0.54-1.31; P = .440). CONCLUSION: Implementation of a statewide PIM restriction rule change effectively reduced the mean number of game-related injuries per season among high school boys' hockey varsity players.

Rab38 targets to lamellar bodies and normalizes their sizes in lung alveolar type II epithelial cells.

Rab38 is a rat Hermansky-Pudlak syndrome gene that plays an important role in surfactant homeostasis in alveolar type II (ATII) pneumocytes. We examined Rab38 function in regulating lamellar body (LB) morphology in ATII cells. Quantitative electron microscopy revealed that LBs in ATII cells were ∼77% larger in Rab38-null fawn-hooded hypertension (FHH) than control Sprague-Dawley (SD) rats. Rab38 protein expression was restricted in lung epithelial cells but was not found in primary endothelial cells. In SD ATII cells, Rab38 protein level gradually declined during 5 days in culture. Importantly, endogenous Rab38 was present in LB fractions purified from SD rat lungs, and transiently expressed enhanced green fluorescent protein (EGFP)-tagged Rab38 labeled only the limiting membranes of a subpopulation (∼30%) of LBs in cultured ATII cells. This selective targeting was abolished by point mutations to EGFP-Rab38 and was not shared by Rab7 and Rab4b, which also function in the ATII cells. Using confocal microscopy, we established a method for quantitative evaluation of the enlarged LB phenotype temporally preserved in cultured FHH ATII cells. A direct causal relationship was established when the enlarged LB phenotype was reserved and then rescued by transiently reexpressed EGFP-Rab38 in cultured FHH ATII cells. This rescuing effect was associated with dynamic EGFP-Rab38 targeting to and on LB limiting membranes. We conclude that Rab38 plays an indispensible role in maintaining LB morphology and surfactant homeostasis in ATII pneumocytes.

Surgical treatment of patients with cervical myeloradiculopathy and coexistent multiple sclerosis: report of 15 patients with long-term follow-up.

STUDY DESIGN: A case series of 15 patients. OBJECTIVE: To report a series of patients with coexisting multiple sclerosis (MS) and progressive myeloradiculopathy who were successfully treated with surgical decompression, fusion, and fixation. SUMMARY OF BACKGROUND DATA: MS and cervical myeloradiculopathy share clinical signs, including gait dysfunction, motor weakness, and hyperreflexia. Distinguishing between these 2 entities may be difficult, and in rare cases they may coexist. Controversy exists regarding the use of surgery in patients with MS as a treatment for degenerative cervical spondylotic disease. METHODS: This case series was composed of 15 patients (10 female, 5 male, average age 50.1 y) with a confirmed diagnosis of MS, who presented with worsening cervical myeloradiculopathy. Outcome measures included neurologic assessment, subjective reports of pain and paraesthesias, and radiographic fusion rates. The patients had neurologic findings consistent with both diseases, and some had radicular findings associated with degenerative disk disease. All patients had magnetic resonance evidence of cervical spinal cord or nerve root compression from an abnormal disk/osteophyte complex, hypertrophied ligament, or both. The average follow-up was 47 months. RESULTS: Thirteen patients showed objective improvement in neurologic function, including increased lower and upper extremity strength. Two patients' symptoms stabilized. Thirteen of 15 patients also had improvement in neck and/or upper extremity pain or paresthesias; 2 patients had continuing upper and lower extremity paresthesias. The patient with bladder incontinence had no improvement of this problem. All patients went on to radiographic fusion. There were no surgical complications. CONCLUSIONS: Patients with coexistent MS and cervical myeloradiculopathy may present a diagnostic challenge, and it may be difficult to ascertain the exact disease pathophysiology. However, patients with MS and degenerative cervical spondylotic disease can benefit from surgical decompression. Surgery is an efficacious, low-risk procedure, and should be offered to appropriately selected patients who harbor both the diseases.