Comprehensive comparison of carotid endarterectomy primary closure and patch angioplasty: A single-institution experience.

BACKGROUND: Carotid endarterectomy (CEA) is an effective intervention for the treatment of high-grade carotid stenosis. Technical preferences exist in the operative steps including the use patch for arteriotomy closure. The goals of this study are to compare the rate of postoperative complications and the rate of recurrent stenosis between patients undergoing primary versus patch closure during CEA. METHODS: Retrospective chart review was conducted for patients who underwent CEA at single institution. Vascular surgeons mainly performed patch closure technique while neurosurgeons used primary closure. Patients' baseline characteristics as well as intraprocedural data, periprocedural complications, and postprocedural follow-up outcomes were captured. RESULTS: Seven hundred and thirteen charts were included for review with mean age of 70.5 years (SD = 10.4) and males representing 64.2% of the cohort. About 49% of patients underwent primary closure while 364 (51%) patients underwent patch closure. Severe stenosis was more prevalent in patients receiving patch closure (94.5% vs. 89.4%; P = 0.013). The incidence of overall complications did not differ between the two procedures (odds ratio = 1.23, 95% confidence intervals = 0.82-1.85; P = 0.353) with the most common complications being neck hematoma, strokes, and TIA. Doppler ultrasound imaging at 6 months postoperative follow-up showed evidence of recurrent stenosis in 15.7% of the primary closure patients compared to 16% in patch closure cohort. CONCLUSION: Both primary closure and patch closure techniques seem to have similar risk profiles and are equally robust techniques to utilize for CEA procedures.

MGluR7 is a presynaptic metabotropic glutamate receptor at ribbon synapses of inner hair cells.

Glutamate is the most pivotal excitatory neurotransmitter in the central nervous system. Metabotropic glutamate receptors (mGluRs) dimerize and can couple to inhibitory intracellular signal cascades, thereby protecting glutamatergic neurons from excessive excitation and cell death. MGluR7 is correlated with age-related hearing deficits and noise-induced hearing loss; however its exact localization in the cochlea is unknown. Here, we analyzed the expression and localization of mGluR7a and mGluR7b in mouse cochlear wholemounts in detail, using confocal microscopy and 3D reconstructions. We observed a presynaptic localization of mGluR7a at inner hair cells (IHCs), close to the synaptic ribbon. To detect mGluR7b, newly generated antibodies were characterized and showed co-localization with mGluR7a at IHC ribbon synapses. Compared to the number of synaptic ribbons, the numbers of mGluR7a and mGluR7b puncta were reduced at higher frequencies (48 to 64 kHz) and in older animals (6 and 12 months). Previously, we reported a presynaptic localization of mGluR4 and mGluR8b at this synapse type. This enables the possibility for the formation of homo- and/or heterodimeric receptors composed of mGluR4, mGluR7a, mGluR7b and mGluR8b at IHC ribbon synapses. These receptor complexes might represent new molecular targets suited for pharmacological concepts to protect the cochlea against noxious stimuli and excitotoxicity.

Homodimerization of a proximal region within the C-terminus of the orphan G-protein coupled receptor GPR179.

G-protein coupled receptors exhibit numerous biological functions. The orphan G-protein coupled receptor GPR179 is a central component of a 1 Megadalton large signalling complex in the ON-pathway of the mammalian retina that assembles multiple proteins, including the metabotropic glutamate receptor mGluR6. Dimer formation is a hallmark of G-protein coupled receptors and some use intracellular C-termini for dimerization. Here we tested the dimerization properties of the intracellular C-terminal domains of mGluR6 and GPR179. While the C-termini of GPR179 and mGluR6 did not interact, we detected a robust homodimerization of a proximal region in the GPR179 C-terminus. Mapping studies defined a linear stretch of 64 amino acids as dimerization region. Bioinformatic analysis indicated that this dimerization region might adopt an α-helical structure that is predicted to dimerize by forming a coiled-coil. Based on these data, we speculate that homodimerization of GPR179 might contribute to the formation of large signalling complexes in the mammalian retina.

Localization of group II and III metabotropic glutamate receptors at pre- and postsynaptic sites of inner hair cell ribbon synapses.

Glutamate is the major excitatory neurotransmitter in the CNS binding to a variety of glutamate receptors. Metabotropic glutamate receptors (mGluR1 to mGluR8) can act excitatory or inhibitory, depending on associated signal cascades. Expression and localization of inhibitory acting mGluRs at inner hair cells (IHCs) in the cochlea are largely unknown. Here, we analyzed expression of mGluR2, mGluR3, mGluR4, mGluR6, mGluR7, and mGluR8 and investigated their localization with respect to the presynaptic ribbon of IHC synapses. We detected transcripts for mGluR2, mGluR3, and mGluR4 as well as for mGluR7a, mGluR7b, mGluR8a, and mGluR8b splice variants. Using receptor-specific antibodies in cochlear wholemounts, we found expression of mGluR2, mGluR4, and mGluR8b close to presynaptic ribbons. Super resolution and confocal microscopy in combination with 3-dimensional reconstructions indicated a postsynaptic localization of mGluR2 that overlaps with postsynaptic density protein 95 on dendrites of afferent type I spiral ganglion neurons. In contrast, mGluR4 and mGluR8b were expressed at the presynapse close to IHC ribbons. In summary, we localized in detail 3 mGluR types at IHC ribbon synapses, providing a fundament for new therapeutical strategies that could protect the cochlea against noxious stimuli and excitotoxicity.-Klotz, L., Wendler, O., Frischknecht, R., Shigemoto, R., Schulze, H., Enz, R. Localization of group II and III metabotropic glutamate receptors at pre- and postsynaptic sites of inner hair cell ribbon synapses.

Furosemide and Albumin for Diuresis of Edema (FADE): A parallel-group, blinded, pilot randomized controlled trial.

PURPOSE: To assess the feasibility of a trial evaluating whether hyperoncotic albumin, in addition to diuretics, improves diuresis and facilitates liberation from mechanical ventilation in critically ill adults. MATERIALS AND METHODS: We randomized 46 hemodynamically stable patients with hypoalbuminemia, prescribed diuretics by treating clinicians, to receive 100 mL of 25% albumin or 0.9% saline placebo BID, for three days, in blinded fashion. We chose five feasibility measurements: enrolment of 50% of eligible patients, at least one patient/week; administration of study treatment within 2 h of diuretics in 85% of patients; completion of study regimen in 80% of patients; and avoidance of open label albumin in 85% of patients. Clinical outcomes included fluid balance, ventilator-free days, and mortality. RESULTS: We randomized 85% of eligible patients. Eighty-four percent received study treatment within 2 h of diuretics, 69% received all doses of study treatment. Study treatment was held in the albumin and placebo groups because of no further need for diuresis (4 vs. 1), hypotension (2 v. 4), and albumin > 35 (1 v. 0). Twenty percent of patients received open-label albumin. Clinical outcomes were similar between groups. CONCLUSIONS: The current study design did not demonstrate feasibility, but can inform the design of a definitive trial.

Independent Heath Facility Meets Cancer Care Ontario and Canadian Association of Gastroenterology Guidelines for Endoscopic Procedure Wait Times While Meeting Quality Indicators: A Retrospective Review.

Background: Canadian independent health facilities (IHFs) have been implemented to reduce hospital endoscopy volume and expedite endoscopic evaluations for patients suspected to have underlying colorectal cancer. Methods: We conducted a retrospective review of a prospective database at a large-volume urban IHF. The primary outcomes were wait times, and the secondary outcomes were colonoscopy quality indicators and complication rates. Results: Median wait times from referral to colonoscopy met the recommendations set out by the Canadian Association of Gastroenterology and Cancer Care Ontario for all indications: chronic abdominal pain: 43 days; new onset change in bowel habits: 36 days; bright red rectal bleeding: 42 days; documented iron-deficiency anemia: 43 days; fecal occult blood test positive: 38 days; cancer likely based on imaging or physical exam: 23 days; chronic diarrhea and chronic constipation: 42 days; and screening colonoscopies: 55 days. Secondary outcomes of quality indicators and complication rates all met or exceeded the CCO and CAG recommendations. Conclusions: This IHF met the recommended wait times for all indications for colonoscopy while maintaining high procedural quality and safety. IHFs are one solution to help meet the increasing demand for colonoscopy in Ontario.

CRIP1a inhibits endocytosis of G-protein coupled receptors activated by endocannabinoids and glutamate by a common molecular mechanism.

The excitability of the central nervous system depends largely on the surface density of neurotransmitter receptors. The endocannabinoid receptor 1 (CB1 R) and the metabotropic glutamate receptor mGlu8 R are expressed pre-synaptically where they reduce glutamate release into the synaptic cleft. Recently, the CB1 R interacting protein cannabinoid receptor interacting protein 1a (CRIP1a) was identified and characterized to regulate CB1 R activity in neurons. However, underlying molecular mechanisms are largely unknown. Here, we identified a common mechanism used by CRIP1a to regulate the cell surface density of two different types of G-protein coupled receptors, CB1 R and mGlu8a R. Five amino acids within the CB1 R C-terminus were required and sufficient to reduce constitutive CB1 R endocytosis by about 72% in the presence of CRIP1a. Interestingly, a similar sequence is present in mGlu8a R and consistently, endocytosis of mGlu8a R depended on CRIP1a, as well. Docking analysis and molecular dynamics simulations identified a conserved serine in CB1 R (S468) and mGlu8a R (S894) that forms a hydrogen bond with the peptide backbone of CRIP1a at position R82. In contrast to mGlu8a R, the closely related mGlu8b R splice-variant carries a lysine (K894) at this position, and indeed, mGlu8b R endocytosis was not affected by CRIP1a. Chimeric constructs between CB1 R, mGlu8a R, and mGlu8b R underline the role of the identified five CRIP1a sensitive amino acids. In summary, we suggest that CRIP1a negatively regulates endocytosis of two different G-protein coupled receptor types, CB1 R and mGlu8a R.