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AbstractRationale, aims, and objectivesNovel health care delivery models are needed to reduce health care use while delivering effective and safe care. We developed a model of a neurologist integrated and colocated in primary care leveraging “curbside,” electronic, and traditional consultations. Our objective was to examine the impact on health care resource use of diagnostic testing and referrals for face‐to‐face neurological consultation and adverse outcomes associated with electronic and curbside consultations.MethodsConsecutive patients from December 1, 2014, to March 13, 2015, were included in the analysis about whom contact was made between a primary care clinician and a colocated neurologist.ResultsOver 3.5 months of the pilot, 359 unique patients generated 429 consultations (179 curbsides, 68 electronic consultations, and 182 face‐to‐face visits). The integrated model resulted in avoidance of 78 face‐to‐face tertiary neurology consultations, 39 brain magnetic resonance imaging, 50 electromyograms, and 53 other advanced imaging studies. Earlier curbside consultation may have prevented unnecessary testing or face‐to‐face tertiary neurology consultations in 40 (22%) patients. Earlier face‐to‐face consultation may have avoided expensive testing in 31 (17%) patients. No cases met criteria for an adverse outcome. The number of referrals to tertiary neurology declined by 64%, and the total number of face‐to‐face visits per month declined by 25%.ConclusionColocated neurology in a primary care medical home offers a promising intervention to deliver high‐value care.

AbstractIntroductionWe hypothesized that common Alzheimer's disease (AD)‐associated variants within the triggering receptor expressed on myeloid (TREM) gene cluster influence disease through gene expression.MethodsExpression microarrays on temporal cortex and cerebellum from ∼400 neuropathologically diagnosed subjects and two independent RNAseq replication cohorts were used for expression quantitative trait locus analysis.ResultsA variant within a DNase hypersensitive site 5′ of TREM2, rs9357347‐C, associates with reduced AD risk and increased TREML1 and TREM2 levels (uncorrected P = 6.3 × 10−3 and 4.6 × 10−2, respectively). Meta‐analysis on expression quantitative trait locus results from three independent data sets (n = 1006) confirmed these associations (uncorrected P = 3.4 × 10−2 and 3.5 × 10−3, Bonferroni‐corrected P = 6.7 × 10−2 and 7.1 × 10−3, respectively).DiscussionOur findings point to rs9357347 as a functional regulatory variant that contributes to a protective effect observed at the TREM locus in the International Genomics of Alzheimer's Project genome‐wide association study meta‐analysis and suggest concomitant increase in TREML1 and TREM2 brain levels as a potential mechanism for protection from AD.

In this review, we highlight that the relationship between muscle sympathetic nerve activity (MSNA) and mean arterial pressure is complex, differs by sex, and changes with age. In young men there is an inverse relationship between MSNA and cardiac output where high MSNA is compensated for by low cardiac output. This inverse relationship is not seen in older men. In young women sympathetic vasoconstriction is offset by β-adrenoreceptor mediated vasodilation, limiting the ability of young women to maintain blood pressure in response to orthostatic stress. However, β-mediated dilation in women is attenuated with age, leading to unopposed α-adrenergic vasoconstriction and a rise in the direct transduction of MSNA into increases in blood pressure. We propose that these changes with age and menopausal status are major contributing factors in the increased prevalence of hypertension in older women. In addition to aging, we highlight that changes in sex hormones in young women (across the menstrual cycle, with oral contraceptive use, or with pregnancy) influence MSNA and the transduction of MSNA into increases in blood pressure. It is likely that the β-adrenergic receptors and/or changes in baroreflex sensitivity play a large role in these sex differences and changes with alterations in sex hormones.

ABSTRACTIntroductionSjögren syndrome is thought to be a lymphocyte‐driven process. Peripheral nervous system involvement occurs in about 20%–25% of patients. A sensory‐predominant, large‐fiber peripheral neuropathy is most common, and it is usually associated with a subacute to chronic presentation.MethodsWe report a rare case of an acute Sjögren‐associated, sensory predominant, length‐dependent peripheral neuropathy mimicking Guillain–Barré syndrome. The patient presented with sensory ataxia preceded by fever and polyarthralgia. She gave a history of years of dry eyes and dry mouth.ResultsShe had a positive Shirmer test, abnormal salivary gland scan, and positive SS‐A and SS‐B antibodies. A sural nerve biopsy showed an unusual, dense, non‐IgG4, polyclonal, plasma‐cell perivascular infiltrate. The patient responded to treatment with weekly pulse intravenous methylprednisolone.ConclusionsSjögren syndrome can present with acute‐onset, sensory predominant peripheral neuropathy. The role of plasma cells in Sjögren syndrome is unexplored and deserves further study. Muscle Nerve 55: 605–608, 2017

AbstractBackgroundLangerhans cell histiocytosis (LCH) is a clonal neoplasm characterized by widely varied clinical presentations, including multisystem involvement and systemic inflammatory symptoms. The AKT pathway is relevant to survival and proliferation of dendritic cells, and is also often upregulated in hematopoietic malignancies. A clinical response in an adult patient with LCH participating in the first‐in‐human trial of afuresertib prompted this prospective trial.ProcedureThe population in the current study included treatment‐naïve (n = 7) and recurrent/refractory patients with LCH (n = 10), who received oral afuresertib (125 mg). The majority of patients were treated for > 24 weeks, with four patients receiving treatment for > 48 weeks.ResultsPharmacokinetic analysis showed similar exposures in previously reported patients with other hematologic malignancies. Primary drug‐related toxicities included Grade 1/2 nausea, diarrhea, dyspepsia, and vomiting. Grade 3 toxicities included fatigue, diarrhea, and pain (one of each). Another severe adverse event involved soft tissue necrosis. The overall response rate in evaluable subjects was 33% in treatment‐naïve patients and 28% in patients with recurrent/refractory disease, which did not meet the predefined Bayesian criteria for efficacy.ConclusionAfuresertib has clinical activity in some patients with newly diagnosed and advanced LCH.