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To assess the feasibility of a prototype insulin infusion set (IIS) for extended wear in adults with type 1 diabetes.The prototype Capillary Biomedical investigational extended-wear IIS (CBX IIS) incorporates a soft, flexible, reinforced kink-resistant angled nylon-derivative cannula with one distal and three proximal ports to optimize insulin delivery. Twenty adult participants with type 1 diabetes established on insulin pump therapy used the CBX IIS for two 7-day test periods while wearing a Dexcom G5 continuous glucose monitor.Participants were able to wear the CBX IIS for an average of 6.6 ± 1.4 days. Eighty-eight percent (36 of 41) of sets were worn for 7 days. No serious adverse events were reported. Five infusion sets failed prematurely because of: unresolvable hyperglycaemia (three); hyperglycaemia with elevated ketones (one); or infection (one). Median time in range (3.9-10.0 mmol/L) was 62% (54-76). Average glucose levels per day of infusion set wear showed a statistically significant increase over time (p .001).Our preliminary observations confirm the tolerability of the prototype CBX IIS for extended wear, albeit with a deterioration in glucose control after the third day.

Insulin exposure varies over 3 days of insulin infusion set (IIS) wear making day-to-day insulin dosing challenging for people with diabetes (PWD). Here we report pharmacodynamic (PD) and pharmacokinetic (PK) data extending these observations to 7 days of IIS wear. PWD (A1C ≤8.5%, C-peptide0.6 nmol/L, ≥6 months pump use) were enrolled in a crossover euglycemic clamp pilot study comparing conventional Teflon angled IISs to an investigational extended-wear IIS. PK/PD data from 6 participants was obtained for 5 hours post-bolus. While PD data were unstable, PK profiles of insulin lispro (0.15 U/kg bolus) show statistically significant, progressive decreases from Day 0 to 7 for tmax (p0.001), t50%(early) (p0.002), t50%(late) (p0.001), and Mean Residence Time (p0.001). AUC0-300 declined by approximately 22% from Day 0 to 7 (n.s.). These results confirm/extend previous observations showing progressive acceleration of insulin exposure over IIS wear time. This may have implications for PWD and designers of closed-loop algorithms, although larger studies are necessary to confirm this.

Insulin exposure and action are known to differ on each of 3 days of infusion set wear during CSII. We extend these observations to 1 week in a pilot phase study comparing conventional Teflon angled infusion sets to a prototype extended wear set using Capillary Biomedical SteadiFlow™ technology. Participants with T1DM for >12 months, A1C Disclosure T.S.Bailey: Advisory Panel; Abbott Diabetes, CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Consultant; LifeScan, Sanofi, Research Support; Abbott Diabetes, Abbott Diagnostics, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Livongo, MannKind Corporation, Medtronic, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita Medical, Senseonics, ViaCyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker's Bureau; Becton, Dickinson and Company, Medtronic, Sanofi. J.R.Kastner: Consultant; Capillary Biomedical, Inc. P.Strange: Other Relationship; Capillary Biomedical, Inc., Stock/Shareholder; Capillary Biomedical, Inc. L.Shi: None. K.A.Oberg: Consultant; Beta Bionics, Inc., Companion Medical, Tandem Diabetes Care, Inc. J.I.Joseph: Advisory Panel; Capillary Biomedical, Inc., Stock/Shareholder; Capillary Biomedical, Inc. P.J.Strasma: Board Member; Capillary Biomedical, Inc., Employee; Capillary Biomedical, Inc., Stock/Shareholder; Capillary Biomedical, Inc. D.B.Muchmore: Consultant; Capillary Biomedical, Inc., Diasome, Zucara Therapeutics, Stock/Shareholder; Capillary Biomedical, Inc., Diasome. Funding National Institutes of Health (2R44DK110969-02)

Cross-β-sheet-rich protein fibrils are infamous for their accumulation in the brains of patients diagnosed with a number of neurodegenerative diseases, including Alzheimer's disease (AD). Disease-relevant fibrils are a result of deviation of the proteins from their native structure to a misfolded state resulting in aggregation and formation of fibrils. In this study, we explored the phenomenon of light-induced fluorescence enhancement of amyloid assemblies stained with two amyloid probes (BSB and K114) using Bombyx mori silk and human AD brain sections. The photoconversion effect, accompanied by an increase in fluorescence intensity and spectral blue-shift, was highly dependent on the chemical structures of the dyes, pH, presence of glycerol and the type of amyloid. The degree of intensity and spectral change over time in response to high laser exposure were quantified and analyzed using custom-written analysis tools. Our findings provide further insight into possible mechanisms of amyloid-mediated photoconversion kinetics of K114 and BSB, and may provide more insight into the molecular nature of various amyloid assemblies.

Gallbladder agenesis is a rare anatomic congenital abnormality caused by the cystic bud failing to develop into the gallbladder. Gallbladder agenesis has a variable presentation, with 50% of patients presenting with symptoms mimicking biliary colic and 35% being incidentally discovered during surgery or autopsy, while another 15% can present with fatal fetal anomalies. In this article, we present a case of gallbladder agenesis in a young woman who presented with biliary-colic-like symptoms suggesting cholecystitis. The gallbladder was not well visualized on ultrasonography, simulating chronic cholecystitis due to shrunken or contracted bladder. Further imaging with computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) helped in the successful diagnosis of gallbladder agenesis and helped prevent unnecessary surgical intervention. Due to the lack of clinical suspicion diagnosing gallbladder agenesis preoperatively is still rare. Persistent symptoms are often associated with biliary colic pain leading to surgery. Conservative management consists of using antispasmodic medications. MRCP may be required to rule out gallbladder agenesis and avoid unnecessary surgery. Gallbladder agenesis can present with symptoms similar to cholecystitis. If the gallbladder is not visualized well on the ultrasound, an additional radiological examination is required. Clinicians' understanding of the condition helps to accurately diagnose the condition preoperatively using the appropriate investigations, thereby minimizing the operative risk to the patient.

Intracranial Masson tumor (intravascular papillary endothelial hyperplasia, IPEH) is a benign lesion that is thought to originate from a reactionary process in response to compromised blood flow. IPEH may be classified into one of three subtypes based on etiology as it may result from the excessive proliferation of endothelial cells within a normal vessel (primary), vascular malformation (type II), or organized hematoma (type III). We report the case of a 79-year-old woman who presented with confusion, gait instability, and urinary incontinence. Neuroimaging revealed a hemorrhagic lesion within the right lateral ventricle, which was successfully resected. To our knowledge, this is the first reported case of an intraventricular IPEH and 33rd case of primary intracranial IPEH. We further performed a systematic review of the literature on all prior type I intracranial IPEH cases and discuss the importance of long-term follow-up in intracranial IPEH.

Despite significant steps in our understanding of Alzheimer's disease (AD), many of the molecular processes underlying its pathogenesis remain largely unknown. Here, we focus on the role of non-coding RNAs produced by small interspersed nuclear elements (SINEs). RNAs from SINE B2 repeats in mouse and SINE Alu repeats in humans, long regarded as "junk" DNA, control gene expression by binding RNA polymerase II and suppressing transcription. They also possess self-cleaving activity that is accelerated through their interaction with certain proteins disabling this suppression. Here, we show that similar to mouse SINE RNAs, human Alu RNAs, are processed, and the processing rate is increased in brains of AD patients. This increased processing correlates with the activation of genes up-regulated in AD patients, while increased intact Alu RNA levels correlate with down-regulated gene expression in AD. In vitro assays show that processing of Alu RNAs is accelerated by HSF1. Overall, our data show that RNAs from SINE elements in the human brain show a similar pattern of deregulation during amyloid beta pathology as in mouse.

The molecular composition of myelin membranes determines their structure and function. Even minute changes to the biochemical balance can have profound consequences for axonal conduction and the synchronicity of neural networks. Hypothesizing that the earliest indication of myelin injury involves changes in the composition and/or polarity of its constituent lipids, we developed a sensitive spectroscopic technique for defining the chemical polarity of myelin lipids in fixed frozen tissue sections from rodent and human. The method uses a simple staining procedure involving the lipophilic dye Nile Red, whose fluorescence spectrum varies according to the chemical polarity of the microenvironment into which the dye embeds. Nile Red spectroscopy identified histologically intact yet biochemically altered myelin in prelesioned tissues, including mouse white matter following subdemyelinating cuprizone intoxication, as well as normal-appearing white matter in multiple sclerosis brain. Nile Red spectroscopy offers a relatively simple yet highly sensitive technique for detecting subtle myelin changes.

Background: Infusion set function remains the limiting factor of insulin pump therapy due to nonmetabolic complications. Here, we tested an investigational extended-wear infusion set prototype with a soft, angled, wire-reinforced cannula with three additional side holes, and compared failure mechanisms and tissue response with a commercial Teflon control. Methods: A total of 48 Teflon and 48 prototype infusion sets were inserted subcutaneously every other day for 14 days in 12 swine and infused with dilute insulin. After two weeks, tissue around cannulas was excised, and occlusions, leaks, and kinks were determined. Tissue was processed and stained to assess the total area of inflammation (TAI) and the inflammatory layer thickness (ILT) around the cannulas. Data were analyzed using Fisher’s exact, analysis of variance-general linear model, Kruskal-Wallis, and post hoc tests. Results: On average, the TAI surrounding the investigational cannula was 52.6% smaller than around the commercial control. The ILT was 66.3% smaller around investigational cannulas. Kinks occurred in 2.1% (investigational) vs 32.4% (commercial) cannulas ( P Conclusions: The data suggest that the infusion set prototype elicits less inflammation over an extended wear time and is resistant to kinking, compared with a commercial Teflon device. This is consistent with previously published data on the impact of cannula material/angle on the inflammatory tissue response. We highlight the following important aspects of infusion set design: (1) secure skin adhesion, (2) reliable cannula insertion, (3) automatic removal of the stylet, (4) cannula material/design that resists kinking, and (5) minimization of local tissue inflammation.

The long-term Implantable Blood Pressure Waveform Monitoring System consists of a miniature applanation tonometer sensor head connected to a battery powered electronics module via a flexible lead. The BP Sensor continuously monitors the arterial BP waveform with data transmitted to a smart phone for real-time data analysis and display. Key data can be transmitted via the cellular network to a central monitoring station for advanced analysis by a computer and clinician. The BP Sensor has been evaluated for safety, accuracy, stability, and reliability for up to 10 months surrounding the external carotid arteries of large canine. Serial ultrasound studies of the artery-sensor interface shows normal artery shape, diameter, and blood flow velocity. BP Sensor performance remained stable for ~ 60 days between calibrations and correlated with reference BP waveform measurement (± 2.5 mm Hg). The BP Sensor head has a novel design that securely couples the diaphragm to the outside wall of a peripheral artery in optimal alignment with minimal flattening (~ 15 %). The Figure below shows the BP Sensor output signal’s detailed BP waveform four months after implantation. The waveform shows subtle and consistent fluctuations in the peaks and valleys of the BP waveform due to positive pressure mechanical ventilation with a respiratory rate of 14 breaths per minute. This is a significant observation which indicates that the BP Sensor has very good sensitivity (± 1 mm Hg) in the normal hemodynamic range (reference BP ~100/60). The real-time and recorded BP Sensor waveform data will be used to make a diagnosis and adjust medication in a more timely and effective manor, leading to improved clinical outcomes.

BackgroundAmyotrophic lateral sclerosis (ALS) is a disabling and rapidly progressive neurodegenerative disorder. Increasing age is an important risk factor for developing ALS, thus the societal impact of this devastating disease will become more profound as the population ages. A significant hurdle to finding effective treatment has been an inability to accurately quantify cerebral degeneration associated with ALS in humans. Advanced magnetic resonance imaging (MRI) techniques hold promise in providing a set of biomarkers to assist in aiding diagnosis and in efficiently evaluating new drugs to treat ALS.MethodsThe Canadian ALS Neuroimaging Consortium (CALSNIC) was founded to develop and evaluate advanced MRI-based biomarkers that delineate biological heterogeneity, track disease progression, and predict survival in a large and heterogeneous sample of ALS patients.FindingsCALSNIC has launched two studies to date (CALSINC-1, CALSNIC-2), acquiring multimodal neuroimaging, neurological, neuropsychological data, and neuropathological data from ALS patients and healthy controls in a prospective and longitudinal fashion from multiple centres in Canada and, more recently, the United States. Clinical and MRI protocols are harmonized across research centres and different MR vendors.InterpretationCALSNIC provides a multicentre platform for studying ALS biology and developing MRI-based biomarkers.FundingCanadian Institutes of Health Research, ALS Society of Canada, Brain Canada Foundation, Shelly Mrkonjic Research Fund

The article published by Kevin Cowart in this issue of the Journal of Diabetes Science and Technology (JDST) is a detailed overview of the clinical trial data and analysis used to demonstrate the safety and effectiveness of the Eversense continuous glucose monitoring (CGM) System for regulatory approval and clinical acceptance. The article describes the published study results for safety, accuracy, reliability, ease of insertion/removal, adverse events, and ease of diabetes patient-use for controlling their glucose levels short and long term. The author nicely compares Eversense CGM System safety and performance with the short-term subcutaneous tissue CGM systems being commercialized by Dexcom, Medtronic Diabetes, and Abbott Diabetes. This comparison may help the clinician define which type of patient with diabetes might benefit the most from the long-term implantable CGM system. The majority of studied patients describe a positive experience managing their diabetes with the Eversense CGM System and request implantation of a new sensor 90 or 180 days later.

Analyzing the breathing data to classify the respiratory states has various applications in the areas of drug overdose and medical diagnosis of several other respiratory medical conditions. Tracheal sounds have shown to provide accurate breathing data with high signal to noise ratio for measuring air flow. The heartbeat signal is a source of interference for the tracheal sound measurements and hence is often filtered out prior to the tracheal sound data analysis. Filtering the heartbeat signal, however, removes a part of the tracheal sound data along with its energy and statistical information. We propose an algorithm to classify the respiratory states from the tracheal sound data despite the presence of heartbeat signals. This algorithm uses the data histogram as well as the data autocorrelation function (ACF) for feature extractions, and shows that these features, when used by a Softmax classifier, can properly discriminate among breathing conditions with classification rates exceeding 97%.

We report a large subconjunctival-orbital granuloma in a 51-year-old male presenting with a blind painful right eye and marked chemosis 15 months after undergoing vitrectomy and silicone oil retinal tamponade for retinal detachment with no reported intraoperative complications. Gross and histopathologic examination of the enucleated eye and episcleral tumor revealed a bosselated mass measuring 17 × 10 × 5 mm containing prominent vacuoles with surrounding epithelioid histiocytes and foreign body multinucleated giant cells. Such a large silicone-induced orbital granuloma following uncomplicated retinal surgery in a grossly intact eye has not been previously reported to the authors’ knowledge. High intraocular pressure and emulsification of oil may facilitate silicone extravasation through scleral wounds after retinal surgery.

This short comunication is a comment on recently published article in AAS by Ylikoski et al. The article stressed the importance of hyperglycemia control awareness and the difficulty of implementation even in a modern hospital setting. 1 When participating in a research study, patients usually get more attention, but despite the research setting in this study, hyperglycemia accrued in over 80% of patients, and none of the hyperglycemic patients were treated according to the hospital guidelines. We are intrigued that 14 years after we presented similar data at the American Society of Anesthesiologists meeting in 2006 (ASA 2006) “Glucose Management in Orthopedic Surgery Patients” not much has changed. We reported that 51 patients had high blood glucose (BG) values (≥15.5 mmol/l), but in only 47% of these cases was the primary physician alerted to assess the patient for a possible change in therapy, as it was the standard protocol in our hospital. Moreover, only four patients (8%) had their glucose management adjusted. On the day of surgery, 21 patients had a BG ≥11.1 mmol/l. However, no cases were canceled including two patients with a BG >16.7 mmol/l. One patient was not diagnosed in the medical record as having diabetes although his preoperative BG was 20.4 mmol/l. Furthermore, his BG was not checked on the morning of the surgery, and yet his first BG was 19.9 mmol/l the night of surgery and 26 mmol/l at 4 am on the first postoperative day. Insulin was not started until 9 am when his BG was 30.5 mmol/l. This emphasizes the importance of glucose control even in patients who are not diagnosed as having diabetes.

Subacute sclerosing panencephalitis (SSPE) is a progressive and eventually fatal neurological disease arising from a persistent infection with measles virus (MV) acquired at a young age. SSPE measles virus strains are defective and unable to produce progeny virions, due to multiple and extensive mutations in a number of key genes. We sequenced the full MV genome from our recently reported SSPE case, which typed as genotype D6, and compared it with other genotype D6 wild type and SSPE sequences. The Alberta D6 strain was significantly different from other reported SSPE D6 sequences. Mutations were observed in all the genes of the Alberta strain, with the greatest sequence divergence noted in the M gene with 17.6% nucleotide and 31% amino acid variation. The L gene showed the least variation with 1.3% nucleotide and 0.7% amino acid differences respectively. The nucleotide variability for 15,672 bases of the complete genome compared to the wild type and other SSPE D6 strains was around 3%.

Endocrine mucin–producing sweat gland carcinoma (EMPSGC) is a slow-growing, rare variant of mucinous carcinoma most commonly presenting on the eyelid.1, 2 Its rarity, inflammatory characteristics, and slow-growing nature all increase the risk of misdiagnosis.2 We present a case of a EMPSGC initially diagnosed as a chalazion. Conservative treatment was attempted on multiple occasions and over an extended period, despite a lack of clinical response. This treatment caused a delay in diagnosis and appropriate treatment for this rare malignant lesion. Our case illustrates EMPSGC as a lesion that can masquerade as a chalazion or hordeolum.

The amygdala is a key anatomic structure that has multiple different nuclei and is involved in several critical aspects of cognition and systemic functions. Several different neurodegenerative diseases have major pathological effects on distinct amygdala nuclei. This presentation will describe the classic and characteristic anatomic distributions in the amygdala of “pure” Alzheimer disease and “pure” Lewy body disease, as well as “normal aging”. In addition, data will be presented on how these classic distributions are altered in either “mixed dementias” or in some atypical forms of neurodegeneration. Amygdala pathology will also be illustrated in several other neurodegenerative diseases. The implications of the differing anatomic distributions in different neurodegenerative diseases will be discussed.LEARNING OBJECTIVESThis presentation will enable the learner to:Recognize key anatomic divisions of the amygdala 1.Describe how different neurodegenerative diseases affect the amygdala2.Consider how anatomic specificity of protein aggregation is important in the classification of neurodegenerative diseases

Background New consumer health devices are being developed to easily monitor multiple physiological parameters on a regular basis. Many of these vital sign measurement devices have yet to be formally studied in a clinical setting but have already spread widely throughout the consumer market. Objective The aim of this study was to investigate the accuracy and precision of heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and oxygen saturation (SpO2) measurements of 2 novel all-in-one monitoring devices, the BodiMetrics Performance Monitor and the Everlast smartwatch. Methods We enrolled 127 patients (>18 years) from the Thomas Jefferson University Hospital Preadmission Testing Center. SBP and HR were measured by both investigational devices. In addition, the Everlast watch was utilized to measure DBP, and the BodiMetrics Performance Monitor was utilized to measure SpO2. After 5 min of quiet sitting, four hospital-grade standard and three investigational vital sign measurements were taken, with 60 seconds in between each measurement. The reference vital sign measurements were calculated by determining the average of the two standard measurements that bounded each investigational measurement. Using this method, we determined three comparison pairs for each investigational device in each subject. After excluding data from 42 individuals because of excessive variation in sequential standard measurements per prespecified dropping rules, data from 85 subjects were used for final analysis. Results Of 85 participants, 36 (42%) were women, and the mean age was 53 (SD 21) years. The accuracy guidelines were only met for the HR measurements in both devices. SBP measurements deviated 16.9 (SD 13.5) mm Hg and 5.3 (SD 4.7) mm Hg from the reference values for the Everlast and BodiMetrics devices, respectively. The mean absolute difference in DBP measurements for the Everlast smartwatch was 8.3 (SD 6.1) mm Hg. The mean absolute difference between BodiMetrics and reference SpO2 measurements was 3.02%. Conclusions Both devices we investigated met accuracy guidelines for HR measurements, but they failed to meet the predefined accuracy guidelines for other vital sign measurements. Continued sale of consumer physiological monitors without prior validation and approval procedures is a public health concern.

There is great clinical need for an insulin infusion set that produces reliable and consistent insulin absorption (PK) from dose to dose and functions reliably for 7 or more days. Capillary Biomedical, Inc. is developing SteadiFlow technology which features a soft yet kink-proof cannula with 1 distal orifice and 3 additional orifices distributed over the final 6 mm of the distal end of the cannula. We compared the performance of the SteadiSet to commercial insulin infusion sets with a Teflon cannula in large ambulatory swine. Investigational infusion sets featuring SteadiFlow technology and commercial Teflon infusion set were inserted into the subcutaneous tissue of swine’s abdomen every other day for 14 days. Insulin lispro (U-5) was infused through the catheters using the same basal/bolus pattern. On day # 14, a 70 ul bolus of insulin/x-ray contrast agent was infused through each CSII catheter. The tissue surrounding each CSII was excised 5 minutes later, frozen, and imaged using a high-resolution micro-CT scanner. The tissue was then processed and stained to produce high-resolution histology images. Histology images revealed a significantly thinner and smaller area of inflammatory tissue around the SteadiSet cannulas compared with the commercial Teflon cannulas. Micro-CT images revealed a significantly larger surface area of insulin/x-ray contrast agent delivered into the adjacent tissue when infused through the SteadiSet infusion sets compared with the commercial infusion sets with a Teflon cannula. A glucose clamp PK/PD study performed in swine using SteadiSet infusion sets implanted for 6 days showed reliable performance and relatively consistent insulin absorption into the circulation. Human clinical trials are planned for early 2019 to evaluate SteadiFlow technology for reliability, glucose control performance, and PK/PD metrics in patients with type 1 diabetes. Disclosure J.I. Joseph: Advisory Panel; Self; CapillaryBiomedical, Inc., Thermalin Diabetes, Inc. Research Support; Self; Capillary Biomedical, inc., Thermalin Diabetes, Inc. Stock/Shareholder; Self; Capillary Biomedical, Inc. M.C. Torjman: Other Relationship; Self; Capillary Biomedical, Inc. C. Loeum: Stock/Shareholder; Self; Capillary Biomedical, Inc. G.J. Eisler: None. P.J. Strasma: Employee; Self; Capillary Biomedical, Inc. A. Khalf: None. Funding JDRF; Capillary Biomedical, Inc.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Contains fulltext : 215228.pdf (Publisher’s version ) (Open Access) Objectives: Handheld medical devices and smartwatches that measure BP without a cuff have recently become available. Since these measurements are relatively more user-friendly than conventional cuff-based measurements they may aid in more frequent BP monitoring. We investigated the accuracy and precision of two popular cuff-less devices: the Everlast smartwatch and the BodiMetrics Performance Monitor.Methods: We enrolled 127 patients from the Thomas Jefferson University Hospital Preadmission Testing Center. Research staff were trained to measure BP according to manufacturer guidelines for the investigational devices. The Everlast smartwatch provides measurements of systolic (SBP) and diastolic (DBP) BP, whereas the Bodimetrics only provides SBP. Reference BP measurements were obtained using a hospital-grade automated sphygmomanometer. After 5 minutes of quiet sitting, four standard and three investigational BP measurements were taken with sixty seconds in between each measurement. The reference BP value was calculated by determining the average of the 2 standard BP measurements that bounded the investigational measurements. We thus determined 3 comparison pairs for each investigational device in each subject. We calculated the mean (SD) of the absolute difference between the respective investigational devices and the reference for SBP and DBP.Results: Data from 42 individuals was excluded because of variation in standard BP measurements per prespecified rules. Of 85 participants used for analysis, 36 (42%) were women, the mean (SD) age was 53 (21) years, 32 (38%) self-reported hypertension, and 97% of these (n = 31) reported taking antihypertensive medications. The average differences between the Everlast watch and reference were 16.9 (13.5) mm Hg for SBP and 8.3 (6.1) mm Hg for DBP. The average difference between the Bodimetrics performance monitor and the reference was 5.3 (4.7) mm Hg for SBP.Conclusions: The Everlast smartwatch and the BodiMetrics Performance Monitor we tested are not accurate enough to be used as BP measurement devices.

This article uses a case-based approach to highlight the clinical features as well as recent advances in molecular genetics, muscle imaging, and pathophysiology of the congenital myopathies.Congenital myopathies refer to a heterogeneous group of genetic neuromuscular disorders characterized by early-onset muscle weakness, hypotonia, and developmental delay. Congenital myopathies are further classified into core myopathies, centronuclear myopathies, nemaline myopathies, and congenital fiber-type disproportion based on the key pathologic features found in muscle biopsies. Genotype and phenotype correlations are hampered by the diverse clinical variability of the genes responsible for congenital myopathies, ranging from a severe neonatal course with early death to mildly affected adults with late-onset disease. An increasing number of genes have been identified, which, in turn, are associated with overlapping morphologic changes in the myofibers. Precise genetic diagnosis has important implications for disease management, including family counseling; avoidance of anesthetic-related muscle injury for at-risk individuals; monitoring for potential cardiac, respiratory, or orthopedic complications; as well as for participation in clinical trials or potential genetic therapies.Collaboration with neuromuscular experts, geneticists, neuroradiologists, neuropathologists, and other specialists is needed to ensure accurate and timely diagnosis based on clinical and pathologic features. An integrated multidisciplinary model of care based on expert-guided standards will improve quality of care and optimize outcomes for patients and families with congenital myopathies.

Summary We present a case of subacute sclerosing panencephalitis that developed in a previously healthy 29-year-old pregnant woman who had returned from a trip to rural India shortly before the onset of symptoms. She was admitted to hospital at 27 weeks' gestation with a history of cognitive decline and difficulty completing simple tasks. She had no clinical signs of infection. The working diagnosis was autoimmune encephalitis, although extensive investigations did not lead to a final classifying diagnosis. The patient became comatose and developed hypertension, and an emergency caesarean section was done at 31 weeks to deliver the child, who seemed healthy. The patient died about 6 weeks after the onset of symptoms. The patient was found to have had subacute sclerosing panencephalitis at autopsy. In this Grand Round, we review the clinical features and treatment of subacute sclerosing panencephalitis, and the epidemiological and public health aspects of the case.

Creutzfeldt–Jakob disease (CJD) is a rapidly progressive neurodegenerative disease that can arise spontaneously, genetically, or be acquired through iatrogenic exposure. Most patients die within a year of symptom onset. It is rare, affecting 1–2 per million per year, and the majority of cases are sporadic. Primary angiitis of the central nervous system (PACNS) is also rare, affecting 2.4 per million per year. We present a case of an unusually long clinical course of CJD, almost five years, which began with symptoms of apraxia. The patient had biopsy-proven PACNS 16 years prior to clinical presentation, and the site of biopsy was the left parietal lobe. Autopsy revealed multicentric prion plaques in the cerebellum, in the setting of normal genetic testing. The presence of plaques in the cerebellum, and prior neurosurgery, raises the possibility of iatrogenic exposure. We present the details of this case, including pathology from the original biopsy and final autopsy, as well as a review of relevant cases in the literature.

Over 1 million people with diabetes use insulin pumps and insert a new continuous subcutaneous insulin infusion (CSII) set every 2-3 days for adequate blood glucose control. Insulin absorption from the subcutaneous tissue is slow and varies over time. This can lead to complications such as hypoglycemia and diabetic ketoacidosis. Furthermore, the repeated trauma of insertion contributes to scar tissue formation and may result in infusion site loss. The development of an extended-wear CSII infusion set that can improve the safety and efficacy of CSII therapy would be a major advantage and facilitate proper glycemic control for diabetic patients. A prototype infusion set was developed using a soft polymer material with multiple ports and tested against commercially available single-port infusion sets in ambulatory large swine. Infusion sets were inserted into the subcutaneous tissue every other day for 8 days. A 70µL bolus of insulin and contrast agent was infused through each cannula 5 minutes prior to excision, then specimens were frozen and Micro-CT imaged. The 3D distribution and surface area of contrast agent in contact with adjacent vascular tissue were evaluated. We hypothesized that multiple-ports would increase fluid dispersion, allowing the insulin to reach more functional capillary and lymph vessels. Investigational sets had a statistically significant larger surface area (p=0.005) and volume (p=0.001) of contrast agent spread when compared with commercial infusion sets, potentially supporting our objective of reaching more vessels to achieve consistent insulin absorption over time. Results from this research have guided the design and development of a next-generation infusion set. Clinical translation of this investigational design could result in a reliable insulin delivery system that simplifies diabetes management, improves quality of life, and benefits clinical outcomes. Disclosure D. Diaz: None. A.R. Dinesen: None. A. Khalf: None. G.J. Eisler: None. C. Loeum: None. M.C. Torjman: Advisory Panel; Self; Capillary Biomedical, Inc. P.J. Strasma: Board Member; Self; Capillary Biomedical, Inc.. Stock/Shareholder; Self; Capillary Biomedical, Inc.. Employee; Self; Capillary Biomedical, Inc. J.I. Joseph: Stock/Shareholder; Self; Capillary Biomedical, Inc.. Advisory Panel; Self; Capillary Biomedical, Inc.. Research Support; Self; Capillary Biomedical, Inc.. Stock/Shareholder; Spouse/Partner; Capillary Biomedical, Inc.. Advisory Panel; Self; Thermalin Diabetes, LLC.. Research Support; Self; Thermalin Diabetes, LLC.. Advisory Panel; Self; Thermalin Diabetes, LLC.. Stock/Shareholder; Self; Thermalin Diabetes, LLC.. Research Support; Self; National Institutes of Health, JDRF. Speaker's Bureau; Self; Capillary Biomedical, Inc..

Subcutaneous (s.c.) glucose sensors have become a key component in type 1 diabetes management. However, their usability is limited by the impact of foreign body response (FBR) on their duration, reliability, and accuracy. Our study gives the first description of human acute and subacute s.c. response to glucose sensors, showing the changes observed in the sensor surface, the inflammatory cells involved in the FBR and their relationship with sensor performance.Twelve obese patients (seven type 2 diabetes) underwent two abdominal biopsies comprising the surrounding area where they had worn two glucose sensors: the first one inserted 7 days before and the second one 24 h before biopsy procedure. Samples were processed and studied to describe tissue changes by two independent pathologists (blind regarding sensor duration). Macrophages quantification was studied by immunohistochemistry methods in the area surrounding the sensor (CD68, CD163). Sensor surface changes were studied by scanning electron microscopy. Seven-day continuous glucose monitoring records were considered inaccurate when mean absolute relative difference was higher than 10%.Pathologists were able to correctly classify all the biopsies regarding sensor duration. Acute response (24 h) was characterized by the presence of neutrophils while macrophages were the main cell involved in subacute inflammation. The number of macrophages around the insertion hole was higher for less accurate sensors compared with those performing more accurately (32.6 ± 14 vs. 10.6 ± 1 cells/0.01 mmThe accumulation of macrophages at the sensor-tissue interface is related with decrease in accuracy of the glucose measure.