Citations

AbstractBackgroundInexpensive, non‐invasive tools for assessing Alzheimer‐type pathophysiologies are needed. Computerized cognitive assessments are prime candidates.MethodsCognitively normal participants, aged 51–71, with magnetic resonance imaging, fluorodeoxyglucose‐positron emission tomography (FDG‐PET), amyloid PET, CogState computerized cognitive assessment, and standard neuropsychological tests were included. We first examined the association between the CogState battery and neuroimaging measures. We then compared that association to the one between standard neuropsychological z‐scores and neuroimaging.ResultsSlower reaction times for CogState Identification and One Back, and lower memory and attention z‐scores, were associated (P < .05) with FDG‐PET hypometabolism. Slower time on the Groton Maze Learning Task and worse One Card Learning accuracy were associated (P < .05) with smaller hippocampal volumes. There were no associations with amyloid PET. Associations of CogState and neuropsychological Z‐scores with neuroimaging were small and of a similar magnitude.ConclusionsCogState subtests were cross‐sectionally comparable to standard neuropsychological tests in their relatively weak associations with neurodegeneration imaging markers.

OBJECT Transfer of the triceps motor branch has been used for treatment of isolated axillary nerve palsy in the adult population. However, there are no published data on the effectiveness of this procedure in the pediatric population with traumatic injuries. The authors reviewed demographics and outcomes in their series of pediatric patients who underwent this procedure. METHODS Six patients ranging in age from 10 to 17 years underwent triceps motor branch transfer for the treatment of isolated axillary nerve injuries between 4 and 8 months after the inciting injury. Deltoid muscle strength was evaluated using the modified British Medical Research Council (MRC) grading system. Shoulder abduction at last follow-up was measured. RESULTS The mean duration of follow-up was 38 months. The average postoperative MRC grading of deltoid muscle strength was 3.6 ± 1.3. The median MRC grade was 4. One patient who did not achieve an MRC grade of 3 suffered multiple injuries from high-velocity trauma. Unlike in the adult population, age, body mass index of the patient, and delay from injury to surgery were not significant factors affecting the outcome of the procedure. CONCLUSIONS In the pediatric population with traumatic injuries, isolated axillary nerve injury treated with triceps motor branch transfer can result in good outcomes.

Elevation of circulating fatty acids (FA) during fasting supports postprandial (PP) insulin secretion that is critical for glucose homeostasis and is impaired in diabetes. We tested our hypothesis that lipid droplet (LD) protein perilipin 5 (PLIN5) in β-cells aids PP insulin secretion by regulating intracellular lipid metabolism. We demonstrated that PLIN5 serves as an LD protein in human islets. In vivo, Plin5 and triglycerides were increased by fasting in mouse islets. MIN6 cells expressing PLIN5 (adenovirus [Ad]-PLIN5) and those expressing perilipin 2 (PLIN2) (Ad-PLIN2) had higher [3H]FA incorporation into triglycerides than Ad-GFP control, which support their roles as LD proteins. However, Ad-PLIN5 cells had higher lipolysis than Ad-PLIN2 cells, which increased further by 8-Br-cAMP, indicating that PLIN5 facilitates FA mobilization upon cAMP stimulation as seen postprandially. Ad-PLIN5 in islets enhanced the augmentation of glucose-stimulated insulin secretion by FA and 8-Br-cAMP in G-protein–coupled receptor 40 (GPR40)- and cAMP-activated protein kinase–dependent manners, respectively. When PLIN5 was increased in mouse β-cells in vivo, glucose tolerance after an acute exenatide challenge was improved. Therefore, the elevation of islet PLIN5 during fasting allows partitioning of FA into LD that is released upon refeeding to support PP insulin secretion in cAMP- and GPR40-dependent manners.

OBJECT Delayed cervical palsy (DCP) is a known complication following cervical spine surgery. While most DCPs eventually improve, they can result in significant temporary disability. Postoperative complications affect hospital length of stay (LOS) as well as overall hospital cost. The authors sought to determine the hospital cost of DCP after cervical spine fusion operations. METHODS A retrospective review of patients undergoing cervical fusion for degenerative disease at the Mayo Clinic from 2008 to 2012 was performed. Patients who developed DCPs not attributable to intraoperative trauma were included. All nonoperative-related costs were compared with similar costs in a control group matched according to age, sex, and surgical approach. All costs and services were reflective of the standard costs for the current year. Raw cost data were presented using ratios due to institutional policy against publishing cost data. RESULTS There were 27 patients (18 men, 9 women) who underwent fusion and developed a DCP over the study period. These patients were compared with 24 controls (15 men, 9 women) undergoing fusion in the same time period. There was no difference between patients and controls in mean age (62.4 ± 3.1 years vs 63.8 ± 2.5 years, respectively; p = 0.74), LOS (4.2 ± 3.3 days vs 3.8 ± 4.5 days, respectively; p = 0.43), or operating room–related costs (1.08 ± 0.09 vs 1.0 ± 0.07, respectively; p = 0.58). There was a significant difference in nonoperative hospital-related costs between patients and controls (1.67 ± 0.15 vs 1.0 ± 0.09, respectively; p = 0.04). There was a significantly higher utilization of postoperative imaging (CT or MRI) in the DCP group (14/27, 52%) when compared with the matched cohort (4/24, 17%; p = 0.018), and a significantly higher utilization of physiatry services (24/27 [89%] vs 15/24 [63%], respectively; p = 0.046). CONCLUSIONS While DCPs did not significantly prolong the length of hospitalization, they did increase hospital-related costs. This method could be further extrapolated to model costs of other complications as well.

Cigarette smoke is a common environmental insult associated with increased risk of developing airway diseases such as wheezing and asthma in neonates and children. In adults, asthma involves airway remodeling characterized by increased airway smooth muscle (ASM) cell proliferation and increased extracellular matrix (ECM) deposition, as well as airway hyperreactivity. The effects of cigarette smoke on remodeling and contractility in the developing airway are not well-elucidated. In this study, we used canalicular-stage (18–20 wk gestational age) human fetal airway smooth muscle (fASM) cells as an in vitro model of the immature airway. fASM cells were exposed to cigarette smoke extract (CSE; 0.5–1.5% for 24–72 h), and cell proliferation, ECM deposition, and intracellular calcium ([Ca 2+ ] i ) responses to agonist (histamine 10 μM) were used to evaluate effects on remodeling and hyperreactivity. CSE significantly increased cell proliferation and deposition of ECM molecules collagen I, collagen III, and fibronectin. In contrast, [Ca 2+ ] i responses were not significantly affected by CSE. Analysis of key signaling pathways demonstrated significant increase in extracellular signal-related kinase (ERK) and p38 activation with CSE. Inhibition of ERK or p38 signaling prevented CSE-mediated changes in proliferation, whereas only ERK inhibition attenuated the CSE-mediated increase in ECM deposition. Overall, these results demonstrate that cigarette smoke may enhance remodeling in developing human ASM through hyperplasia and ECM production, thus contributing to development of neonatal and pediatric airway disease.

SummarySphingomyelin metabolism has been linked to several diseases and to longevity. However, few epidemiological studies have quantified individual plasma sphingomyelin species (identified by acyl‐chain length and saturation) or their relationship between demographic factors and disease processes. In this study, we determined plasma concentrations of distinct sphingomyelin species in 992 individuals, aged 55 and older, enrolled in the Baltimore Longitudinal Study of Aging. Participants were followed, with serial measures, up to 6 visits and 38 years (3972 total samples). Quantitative analyses were performed on a high‐performance liquid chromatography‐coupled electrospray ionization tandem mass spectrometer. Linear mixed models were used to assess variation in specific sphingomyelin species and associations with demographics, diseases, medications or lifestyle factors, and plasma cholesterol and triglyceride levels. We found that most sphingomyelin species increased with age. Women had higher plasma levels of all sphingomyelin species and showed steeper trajectories of age‐related increases compared to men. African Americans also showed higher circulating sphingomyelin concentrations compared to Caucasians. Diabetes, smoking, and plasma triglycerides were associated with lower levels of many sphingomyelins and dihydrosphingomyelins. Notably, these associations showed specificity to sphingomyelin acyl‐chain length and saturation. These results demonstrate that longitudinal changes in circulating sphingomyelin levels are influenced by age, sex, race, lifestyle factors, and diseases. It will be important to further establish the intra‐individual age‐ and sex‐specific changes in each sphingomyelin species in relation to disease onset and progression.

Object Swallowing dysfunction is common following transoral (TO) odontoidectomy. Preliminary experience with newer endoscopic transnasal (TN) approaches suggests that dysphagia may be reduced with this alternative. However, the reasons for this are unclear. The authors hypothesized that the TN approach results in less disruption of the pharyngeal plexus and anatomical structures associated with swallowing. The authors investigate the histological and gross surgical anatomical relationship between pharyngeal plexus innervation of the upper aerodigestive tract and the surgical approaches used (TN and TO). They also review the TN literature to evaluate swallowing outcomes following this approach. Methods Seven cadaveric specimens were used for histological (n = 3) and gross anatomical (n = 4) examination of the pharyngeal plexus with the TO and TN surgical approaches. Particular attention was given to identifying the location of cranial nerves (CNs) IX and X and the sympathetic chain and their contributions to the pharyngeal plexus. S100 staining was performed to assess for the presence of neural tissue in proximity to the midline, and fiber density counts were performed within 1 cm of midline. The relationship between the pharyngeal plexus, clivus, and upper cervical spine (C1-3) was defined. Results Histological analysis revealed the presence of pharyngeal plexus fibers in the midline and a significant reduction in paramedian fiber density from C-2 to the lower clivus (p < 0.001). None of these paramedian fibers, however, could be visualized with gross inspection or layer-by-layer dissection. Laterally based primary pharyngeal plexus nerves were identified by tracing their origins from CNs IX and X and the sympathetic chain at the skull base and following them to the pharyngeal musculature. In addition, the authors found 15 studies presenting 52 patients undergoing TN odontoidectomy. Of these patients, only 48 had been swallowing preoperatively. When looking only at this population, 83% (40 of 48) were swallowing by Day 3 and 92% (44 of 48) were swallowing by Day 7. Conclusions Despite the midline approach, both TO and TN approaches may injure a portion of the pharyngeal plexus. By limiting the TN incision to above the palatal plane, the surgeon avoids the high-density neural plexus found in the oropharyngeal wall and limits injury to oropharyngeal musculature involved in swallowing. This may explain the decreased incidence of postoperative dysphagia seen in TN approaches. However, further clinical investigation is warranted.

Transplant‐associated thrombotic microangiopathy (TA‐TMA) is a rare clinical syndrome associated with significant mortality. Although the use of plasma exchange (PE) in TA‐TMA continues to be explored, evidence for its efficacy is debated. We performed a single institution, retrospective study to evaluate the efficacy of PE in treating TA‐TMA patients. Special attention was given to efficacy in relation to the timing of presentation with TA‐TMA since transplant. Thirty‐three patients diagnosed with TA‐TMA and treated with PE between January 1999 and December 2010 were included in the study. Clinical improvement was seen in eight patients (24%); four patients achieved complete resolution while the remaining four achieved partial resolution. All‐cause day‐30 and day‐100 mortality was 33 and 55%, respectively. There was a trend toward a better outcome (complete/partial) for those presenting ≥ 100 days after transplantation (42%) vs. < 100 days after transplantation (14%; P‐value = 0.15). Similarly, those presenting at ≥ 100 days had better, but not significantly, 30‐day and 100‐day all‐cause mortality rates (17 and 33%, respectively) than those presenting at < 100 days (43 and 67%, respectively) (P‐value = 0.25 and 0.08, for 30‐ and 100‐day all‐cause mortality, respectively). This is the first study looking at the efficacy of PE while considering the time of presentation since transplantation and is one of the largest single institution series of TA‐TMA. The overall efficacy of PE is poor; however, patients who present with TA‐TMA ≥100 days after transplant may have better outcome and lower mortality. J. Clin. Apheresis 30:147–153, 2015. © 2014 Wiley Periodicals, Inc.

Inherited forms of amyloidosis are rare; of these, transthyretin‐related (ATTR) is the most common, but non‐ATTR has been described as well. We studied a large case series of ATTR and a small series of non‐ATTR to better determine the mutation frequencies and geographic distributions of these inherited forms of amyloidosis in the United States. We performed a retrospective cross‐sectional study of 284 ATTR and non‐ATTR patients seen at Mayo Clinic in Rochester, Minnesota, from 1 January 1970 through 29 January 2013. Mutations were identified by DNA sequencing, restriction fragment length polymorphism, or mass spectroscopy. The genetic testing method was unknown for several patients, but a small proportion were identified by family history or by classical clinical presentation associated with a specific mutation. The most common ATTR mutations were Thr60Ala (24%), Val30Met (15%), Val122Ile (10%), and Ser77Tyr (5%). Non‐ATTR mutations included gelsolin (n = 3), apolipoprotein A‐I (n = 6), apolipoprotein A‐II (n = 1), fibrinogen A‐α (n = 9), and lysozyme (n = 1). Although rare, ATTR and, to a lesser extent, non‐ATTR are prevalent in the United States and should be considered for patients presenting in the appropriate clinical context.