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Health care quality, a key concept for medical practice and research, is also a widely used construct in health care administration and marketing research. We explored discipline-specific differences in the definition of quality, with the intent of finding a more unified approach. We summarized definitions and basic conceptual approaches to quality in both disciplines and then compared them on several attributes: basic goals, sources of measurement, role of patient perceptions, role of health care personnel, and need for risk adjustment. We developed a conceptual model combining the 2 approaches. Both disciplines could benefit from broadening their outcome measures. Patient satisfaction deserves more attention from medical researchers, whereas marketing approaches should go beyond using patient satisfaction as the only outcome of interest. It is conceptually feasible to integrate medical and marketing approaches to quality, with important insights resulting from this integration. [ABSTRACT FROM AUTHOR]

Background: Although pulmonary vein isolation (PVI) remains the cornerstone of catheter ablation of atrial fibrillation (AF), several studies have illustrated clinical benefits associated with PVI with posterior wall isolation (PWI)., Methods: This retrospective study investigated the outcomes of PVI alone versus PVI+PWI performed using the cryoballoon in patients with cardiac implantable electronic devices (CIEDs) and paroxysmal AF (PAF) or persistent AF (PersAF)., Results: Acute PVI was achieved in all patients using cryoballoon ablation. Compared to PVI alone, PVI+PWI was associated with longer cryoablation, fluoroscopy, and total procedure times. Adjunct radiofrequency was required to complete PWI in 29/77 patients (37.7%). Adverse events were similar with PVI alone versus PVI+PWI. But at 24 ± 7 months of follow-up, not only cryoballoon PVI+PWI was associated with improved freedom from recurrent AF (74.3% vs. 46.0%, P = .007) and all atrial tachyarrhythmias (71.4% vs. 38.1%, P = .001) in patients with PersAF, cryoballoon PVI+PWI also yielded greater freedom from AF (88.1% vs. 63.7%, P = .003) and all atrial tachyarrhythmias (83.3% vs. 60.8%, P = .008) in those with PAF. Additionally, PVI+PWI was associated with higher reductions in atrial tachyarrhythmia burden (97.9% vs. 91.6%, P < .001), need for cardioversion (5.2% vs. 23.6%, P < .001) and repeat catheter ablation (10.4% vs. 26.1%, P = .005), and a longer time-to-arrhythmia recurrence (16 ± 6 months vs. 8 ± 5 months, P < .001) in both PersAF and PAF patients., Conclusion: In CIED patients with PersAF or PAF, cryoballoon PVI+PWI is associated with a greater freedom from recurrent AF and atrial tachyarrhythmias, as compared to PVI alone during long-term follow-up., (© 2023 Wiley Periodicals LLC.)

Objectives: To determine whether the initial radiographic displacement of humeral shaft fractures is associated with failure of nonoperative management., Design: Retrospective cohort study., Setting: Urban level 1 trauma center., Patients/participants: 106 patients with humeral shaft fractures (OTA/AO 12) initially managed nonoperatively., Intervention: Functional bracing., Main Outcome Measurements: Failure of nonoperative management, defined as conversion to surgery, malunion, and delayed union/nonunion., Results: Nonoperative management failed in 33 (31%) of 106 included patients with 27 patients (25%) requiring surgery. On multivariate analysis, female sex [odds ratio (OR): 3.50, 95% confidence interval (CI): 1.09 to 11.21], American Society of Anesthesiologist classification >1 (OR: 7.16, CI: 1.95 to 26.29), initial fracture medial/lateral (ML) translation (OR: 1.09, CI: 1.01 to 1.17, per unit change), and initial fracture anterior-posterior (AP) angulation (OR: 1.09, CI: 1.02 to 1.15, per unit change) were independently associated with failure of nonoperative management. Initial fracture displacement values that maximized the sensitivity (SN) and specificity (SP) for failure included an AP angulation >11 degrees (SN 75%, SP 64%) and ML translation >12 mm (SN 55%, SP 75%). The failure rate in patients with none, 1, or both of these fracture parameters was 3.1% (1/32), 35.6% (20/56), and 66.6% (12/18), respectively., Conclusions: Nearly one-third of patients experienced failure of initial nonoperative management. Failure was found to be associated with greater initial fracture AP angulation and ML translation. Fracture displacement cut-off values were established that may be used by surgeons to counsel patients with these injuries., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Prior studies have demonstrated clinical benefits associated with cryoballoon pulmonary vein isolation (PVI) and concomitant posterior wall isolation (PWI) in patients with persistent atrial fibrillation (AF). However, the role for this approach in patients with paroxysmal atrial fibrillation (PAF) remains unclear., Objectives: This study investigated the acute and long-term outcomes of PVI vs PVI+PWI using cryoballoon in patients with symptomatic PAF., Methods: This retrospective study (NCT05296824) examined the outcomes of cryoballoon PVI (n = 1,342) vs cryoballoon PVI+PWI (n = 442) in patients with symptomatic PAF during long-term follow-up. Using the nearest-neighbor method, a 1:1 matched sample of patients receiving PVI alone and PVI+PWI was created., Results: The matched cohort consisted of 320 patients (PVI: n = 160; PVI+PWI: n = 160). PVI+PWI was associated with longer cryoablation (23 ± 10 minutes vs 42 ± 11 minutes; P < 0.001) and procedure times (103 ± 24 minutes vs 127 ± 14 minutes; P < 0.001). In 39 (24.4%) of 160 patients, adjunct radiofrequency ablation was required for PVI+PWI. Adverse event rates were similar (PVI 3.8% vs PVI+PWI 1.9%; P = 0.31). Though there were no differences at 12 months, freedom from all atrial arrhythmias (67.5% vs 45.0%; P < 0.001) and AF (75.6% vs 55.0%; P < 0.001) were significantly greater with PVI+PWI vs PVI alone at 39 ± 9 months of follow-up. PVI+PWI was also associated with reduced long-term need for cardioversion (16.9% vs 27.5%; P = 0.02) and repeat catheter ablation (11.9% vs 26.3%; P = 0.001), and emerged as the only significant predictor of freedom from recurrent AF (HR: 2.79; 95% CI: 1.64-4.74; P < 0.001)., Conclusions: Compared with cryoballoon PVI, cryoballoon PVI+PWI appears to be associated with greater freedom from recurrent atrial arrhythmias and AF in patients with PAF during long-term follow-up >3 years., Competing Interests: Funding Support and Author Disclosures Drs Aryana, O’Neill, Ellis, and d’Avila have received consulting fees from Medtronic. Dr Aryana has received research grant support from Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Due to their internal rotating magnets, conventional impeller-driven percutaneous ventricular assist devices (PVADs) yield high-frequency electrogram artifact and electromagnetic interference (EMI) when used with magnetic-based 3D electroanatomic mapping systems. The new percutaneous heart pump (PHP; Abbott, Chicago, IL) is a 14-French, 5-L/min, impeller axial-flow PVAD with a novel design that utilizes an external motor., Methods: We evaluated the feasibility of 3D mapping and radiofrequency ablation (RFA) in vivo during PHP mechanical circulatory support (MCS) in simulated ventricular tachycardia (pacing at 300 ms) and ventricular flutter (VFL, pacing at 200 ms) and also during ventricular fibrillation (VF) in a porcine model. Anterograde (right ventricular), transseptal, retrograde, and epicardial right and left ventricular 3D mapping (EnSite/CARTO) and RFA were performed in 6 swine using high-density mapping and force-sensing RFA catheters (TactiCath/ThermoCool). Surface and intracardiac electrograms and 3D maps were analyzed for noise/interference with and without MCS using PHP in sinus rhythm and simulated VT/VFL and VF., Results: Mapping and RFA proved feasible in the presence of MCS using PHP. The mean arterial pressure in sinus rhythm was 55 ± 2 mmHg (baseline) and 84 ± 4 mmHg during MCS with PHP and well-maintained during simulated VT (73 ± 8 mmHg) and VFL (65 ± 2 mmHg) and even in VF (65 ± 5 mmHg). No electrogram noise/artifact, EMI, or 3D map distortions were observed during mapping/RFA with either of two mapping systems., Conclusions: Endocardial and epicardial 3D mapping and RFA in the presence of PHP are feasible and offer significant MCS during simulated VT/VFL and VF. Furthermore, PHP yielded no electrogram noise/artifact, EMI, or 3D mapping distortions in conjunction with magnetic-based 3D mapping systems., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The Bone Metastases Ensemble Trees for Survival Decision Support Platform (BMETS-DSP) provides patient-specific survival predictions and evidence-based recommendations to guide multidisciplinary management for symptomatic bone metastases. We assessed the clinical utility of the BMETS-DSP through a pilot prepost design in a simulated clinical environment., Methods: Ten Radiation Oncology physicians reviewed 55 patient cases at two time points: without and then with the use of BMETS-DSP. Assessment included 12-month survival estimate, confidence in and likelihood of sharing estimates with patients, and recommendations for open surgery, systemic therapy, hospice referral, and radiotherapy (RT) regimen. Paired statistics compared pre- versus post-DSP outcomes. Reported statistical significance is P < .05., Results: Pre- versus post-DSP, overestimation of true minus estimated survival time was significantly reduced (mean difference -2.1 [standard deviation 4.1] v -1 month [standard deviation 3.5]). Prediction accuracy was significantly improved at cut points of < 3 (72 v 79%), ≤ 6 (64 v 71%), and ≥ 12 months (70 v 81%). Median ratings of confidence in and likelihood of sharing prognosis significantly increased. Significantly greater concordance was seen in matching use of 1-fraction RT with the true survival < 3 months (70 v 76%) and < 10-fraction RT with the true survival < 12 months (55 v 62%) and appropriate use of open surgery (47% v 53%), without significant changes in selection of hospice referral or systemic therapy., Conclusion: This pilot study demonstrates that BMETS-DSP significantly improved physician survival estimation accuracy, prognostic confidence, likelihood of sharing prognosis, and use of prognosis-appropriate RT regimens in the care of symptomatic bone metastases, supporting future multi-institutional validation of the platform., Competing Interests: Sara R. AlcornEmployment: University of MinnesotaHonoraria: Allegheny Health NetworkResearch Funding: Radiation Oncology Institute (ROI), Pfizer-Prostate Cancer Foundation Jacob FikselEmployment: Janssen, VertexPatents, Royalties, Other Intellectual Property: I am listed on US patent No. 10,975,431, for cell-free DNA for assessing and/or treating cancer. I am not the main inventor and have not received any royalties Chen HuConsulting or Advisory Role: D1 Medical Technology Lawrence KleinbergConsulting or Advisory Role: NovocureResearch Funding: Novartis (Inst), Bristol Myers Squibb/Medarex (Inst), Incyte Adam LevinLeadership: Ensysce BiosciencesStock and Other Ownership Interests: Ensysce BiosciencesConsulting or Advisory Role: Ensysce BiosciencesPatents, Royalties, Other Intellectual Property: Patent Pending (Inst) Thomas SmithEmployment: UpToDateHonoraria: Athenex, Association of Community Cancer Centers (ACCC)Patents, Royalties, Other Intellectual Property: Royalties from Oxford Textbook of Cancer Communication, coeditorOpen Payments Link: https://openpaymentsdata.cms.gov/physician/202382/general-payments Zhi ChengEmployment: Siemens Healthineers (I)Research Funding: Toshiba (Inst)Patents, Royalties, Other Intellectual Property: Patents and royalties (Inst) Lindsey SloanEmployment: University of Minnesota (I)Consulting or Advisory Role: Sanofi/Regeneron (I)Research Funding: Arena Pharma (I) K. Ranh VoongHonoraria: Physicians' Education Resource LLCConsulting or Advisory Role: AstraZenecaTravel, Accommodations, Expenses: Prime Oncology Todd R. McNuttStock and Other Ownership Interests: Oncospace LLCResearch Funding: Canon Medical System (Inst), Oncospace LLC (Inst)Patents, Royalties, Other Intellectual Property: Radiation Dose Calculation Algorithm Michael R. BowersEmployment: Oncospace IncStock and Other Ownership Interests: Oncospace Inc Theodore L. DeWeeseStock and Other Ownership Interests: Digital HarmonicPatents, Royalties, Other Intellectual Property: Patent pending on the computer algorithm in radiation therapy planning Scott ZegerLeadership: Embold Health Jean L. WrightEmployment: Johns Hopkins HospitalHonoraria: American Society for Radiation OncologyResearch Funding: OncospacePatents, Royalties, Other Intellectual Property: Spouse receives royalties from Up To Date (I)Expert Testimony: Marshall DennehyNo other potential conflicts of interest were reported.

Purpose: There is a growing interest in performing pulmonary vein isolation (PVI) with concomitant posterior wall isolation (PWI) using the cryoballoon for the treatment of patients with persistent atrial fibrillation (AF). However, there is little known about the long-term durability of PWI using this approach., Methods: In this multicenter study, we retrospectively examined the durability of PVI + PWI using the 28-mm cryoballoon by investigating the outcomes from consecutive patients referred for repeat catheter ablation., Results: Altogether, 81/519 patients (15.6%) were referred for repeat catheter ablation. Repeat ablation was associated with a longer AF duration, hypertension, heart failure, multiple cardioversions, and antiarrhythmic therapy as well as larger left atrial (LA) diameters (49 ± 4 mm versus 43 ± 5 mm; P < 0.001) and greater need for "touch-up" (adjunct) radiofrequency ablation (44.4% versus 18.3%; P < 0.001). LA diameter also emerged as a significant predictor for adjunct radiofrequency ablation (P < 0.001). Durable PVI was observed in 66/81 patients (81.5%) and PWI in 67/81 patients (82.7%). Those with incomplete PWI exhibited larger LA diameters, particularly > 48 mm (negative predictive value = 89.7%). Lastly, an atypical LA posterior wall/roof flutter represented the third most common cause of arrhythmia recurrence and essentially every patient with incomplete PWI exhibited such an arrhythmia., Conclusion: PWI performed using a 28-mm cryoballoon in conjunction with PVI exhibits long-term durability in the vast majority of patients with persistent AF. While LA diameter (particularly > 48 mm) is a significant predictor for the need for adjunct radiofrequency ablation when performing this technique, those with incomplete PWI invariably present with an atypical flutter using this substrate., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: The aim of this multicenter, randomized, single-blind study was to prospectively evaluate the short-and long-term outcomes of pulmonary vein isolation (PVI) versus PVI with concomitant left atrial posterior wall isolation (PWI) using the cryoballoon in patients with symptomatic persistent/long-standing persistent atrial fibrillation (P/LSP-AF)., Background: Some studies have suggested a clinical benefit associated with PVI+PWI in patients with P/LSP-AF. However, there are limited safety and efficacy data on this approach using cryoballoon ablation., Methods: The immediate and long-term outcomes in patients with P/LSP-AF randomized to PVI (n = 55) versus PVI+PWI (n = 55) using the cryoballoon were prospectively examined., Results: Baseline characteristics were similar. PVI was achieved in all patients (21 ± 11 min). PWI was attained using 23 ± 8 min of cryoablation. Adjunct radiofrequency ablation was required in 4 of 110 patients (7.3%) to complete PVI (3 ± 2 min) and in 25 of 55 patients (45.5%) to complete PWI (4 ± 6 min). Although left atrial dwell time (113 ± 31 min vs. 75 ± 32 min; p < 0.001) and total procedure time (168 ± 34 min vs. 127 ± 40 min; p < 0.001) were longer with PVI+PWI, this cohort required fewer intraprocedural cardioversions (89.1% vs. 96.4%; p = 0.04). Adverse events occurred in 5.5% in each group (p = 1.00). However, the incidence of recurrent atrial fibrillation at 12 months was significantly lower with PVI+PWI (25.5% vs. 45.5%; p = 0.028). Additionally, in a multivariate analysis, PVI+PWI emerged as a significant predictor of freedom from recurrent atrial fibrillation (odds ratio: 3.67; 95% confidence interval: 1.44 to 9.34; p = 0.006)., Conclusions: In patients with P/LSP-AF, PVI+PWI using the cryoballoon is associated with a significant reduction in atrial fibrillation recurrence, but similar safety, as compared with PVI alone., Competing Interests: Funding Support and Author Disclosures Drs. Aryana, Bowers, Natale, O’Neill, and Okishige have received consulting fees and speaking honoraria from Medtronic. Drs. Aryana and O’Neill have received research grants from Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: It is common practice to observe patients during an overnight stay (ONS) following a catheter ablation procedure for the treatment of atrial fibrillation (AF)., Objectives: To investigate the safety and economic impact of a same-day discharge (SDD) protocol after cryoballoon ablation for treatment of AF in high-volume, geographically diverse US hospitals., Methods: We retrospectively reviewed 2374 consecutive patients (1119 SDD and 1180 ONS) who underwent cryoballoon ablation for AF at three US centers. Baseline characteristics, acute procedure-related complications, and longer-term evaluations of safety were recorded during routine clinical follow-up. The mean cost of an ONS was used in a one-way sensitivity analysis to evaluate yearly cost savings as a function of the percentage of SDD cases per year., Results: The SDD and ONS cohorts were predominately male (69% vs. 67%; p = .3), but SDD patients were younger (64 ± 11 vs. 66 ± 10; p < .0001) with lower body mass index (30 ± 6 vs. 31 ± 61; p < .0001) and CHA 2 DS 2 -VASc scores (1.4 ± 1.0 vs. 2.2 ± 1.4; p < .0002). There was no difference between SDD and ONS in the 30-day total complication rate (n = 15 [1.26%] versus n = 24 [2.03%]; p = .136, respectively). The most common complication was hematoma in both the SDD (n = 8; 0.67%) and ONS (n = 11; 0.93%) cohorts. Sensitivity analysis demonstrated that when 50% of every 100 patients treated were discharged the same day, hospital cost savings ranged from $45 825 to $83 813 per year across US hospitals., Conclusions: SDD following cryoballoon ablation for AF appears to be safe and is associated with cost savings across different US hospitals., (© 2020 Wiley Periodicals LLC.)

Following nerve stimulation, there are two distinct phases of Ca2+-dependent neurotransmitter release: a fast, synchronous release phase, and a prolonged, asynchronous release phase. Each of these phases is tightly regulated and mediated by distinct mechanisms. Synaptotagmin 1 is the major Ca2+ sensor that triggers fast, synchronous neurotransmitter release upon Ca2+ binding by its C2A and C2B domains. It has also been implicated in the inhibition of asynchronous neurotransmitter release, as blocking Ca2+ binding by the C2A domain of synaptotagmin 1 results in increased asynchronous release. However, the mutation used to block Ca2+ binding in the previous experiments (aspartate to asparagine mutations, sytD-N) had the unintended side effect of mimicking Ca2+ binding, raising the possibility that the increase in asynchronous release was directly caused by ostensibly constitutive Ca2+ binding. Thus, rather than modulating an asynchronous sensor, sytD-N may be mimicking one. To directly test the C2A inhibition hypothesis, we utilized an alternate C2A mutation that we designed to block Ca2+ binding without mimicking it (an aspartate to glutamate mutation, sytD-E). Analysis of both the original sytD-N mutation and our alternate sytD-E mutation at the Drosophila neuromuscular junction showed differential effects on asynchronous release, as well as on synchronous release and the frequency of spontaneous release. Importantly, we found that asynchronous release is not increased in the sytD-E mutant. Thus, our work provides new mechanistic insight into synaptotagmin 1 function during Ca2+-evoked synaptic transmission and demonstrates that Ca2+ binding by the C2A domain of synaptotagmin 1 does not inhibit asynchronous neurotransmitter release in vivo., Competing Interests: The authors have declared that no competing interests exist.

Synaptic transmission relies on the fast, synchronous fusion of neurotransmitter filled vesicles with the presynaptic membrane. Synaptotagmin is the Ca 2+ sensor that couples the Ca 2+ influx into nerve terminals following an action potential with this fast, synchronous vesicle fusion. Over two decades of synaptotagmin research has provided many clues as to how Ca 2+ binding by synaptotagmin may lead to vesicle fusion. In vitro studies of molecular binding interactions are essential for elucidating potential mechanisms. However, an in vivo system to evaluate the postulated mechanisms is required to determine functional significance. The neuromuscular junction (NMJ) has long been an indispensable tool for synaptic research and studies at the NMJ will undoubtedly continue to provide key insights into synaptotagmin function., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2020. Published by Elsevier B.V.)

The synaptic vesicle protein, synaptotagmin, is the principle Ca2+ sensor for synaptic transmission. Ca2+ influx into active nerve terminals is translated into neurotransmitter release by Ca2+ binding to synaptotagmin's tandem C2 domains, triggering the fast, synchronous fusion of multiple synaptic vesicles. Two hydrophobic residues, shown to mediate Ca2+-dependent membrane insertion of these C2 domains, are required for this process. Previous research suggested that one of its tandem C2 domains (C2B) is critical for fusion, while the other domain (C2A) plays only a facilitatory role. However, the function of the two hydrophobic residues in C2A have not been adequately tested in vivo. Here we show that these two hydrophobic residues are absolutely required for synaptotagmin to trigger vesicle fusion. Using in vivo electrophysiological recording at the Drosophila larval neuromuscular junction, we found that mutation of these two key C2A hydrophobic residues almost completely abolished neurotransmitter release. Significantly, mutation of both hydrophobic residues resulted in more severe deficits than those seen in synaptotagmin null mutants. Thus, we report the most severe phenotype of a C2A mutation to date, demonstrating that the C2A domain is absolutely essential for synaptotagmin's function as the electrostatic switch., Competing Interests: The authors have declared that no competing interests exist.

A multimodal pain management strategy combines complementary medications and techniques, targeting unique pathways, to improve overall analgesic effect and reduce opioid requirements. In this 2-part review, we examine the literature identifying nonopioid analgesic modalities and their targets in the pain pathway as well as anesthetic techniques found to be opioid sparing in the practice of upper extremity surgery. Part 1 focused on operative anesthesia and analgesia. In part 2, we discuss the nonopioid options available after surgery and explore areas for future investigation specific to upper extremity surgery., (Copyright © 2019 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

A multimodal pain management strategy combines complementary medications and techniques, targeting unique pathways, to improve overall analgesic effect and reduce opioid requirements. In this 2-part review, we examine the literature identifying nonopioid analgesic modalities and their targets in the pain pathway as well as anesthetic techniques found to be opioid-sparing in the practice of upper extremity surgery. First, we focus on operative anesthesia and analgesia and areas for future research specific to upper extremity surgery. In part 2, we discuss the nonopioid options available after surgery., (Copyright © 2019 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Objectives: The Functional Assessment of Cancer Therapy (FACT) instrument is comprised of a group of related and overlapping quality of life (QoL) questionnaires including a core general form, head and neck cancer (HNC)-specific items, and an expert-selected index (FACT-HNSI). Understanding how these relate to more HNC-specific instruments such as the MD Anderson Dysphagia Inventory (MDADI) and Sydney Swallow Questionnaire (SSQ) is vital for guiding their use in clinical trials., Materials and Methods: HNC patients concurrently completed MDADI, SSQ, and FACT questionnaires at radiation oncology clinic visits (2015-2016). Spearman correlation coefficients were calculated between each FACT instrument and MDADI or SSQ. Unsupervised k-means cluster analyses were performed to identify clusters of similar QoL responses. Principal component analysis (PCA) identified the degree of variability explained by each instrument., Results: We identified 631 instances (363 patients) where the questionnaires were completed concurrently. Correlations between the various FACT measures and SSQ or MDADI were all significant (p < 0.001), but FACT HNC-specific subscale and FACT-HNSI showed the strongest correlation with MDADI and SSQ. Clustering identified 3 distinct groups of responses when combining instruments either pairwise or three-way. PCA revealed that MDADI and FACT HNC-specific subscale provide similar and likely redundant information., Conclusion: FACT HNC-subscale and FACT-HNSI may be preferable over other FACT measures for use in clinical trials where patient-reported swallow function is evaluated. MDADI and FACT provide similar insights into HNC patient QoL while SSQ provides additional, complementary information which could serve to better stratify patients into groups with high, medium, and low QoL outcomes., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Pulmonary vein isolation (PVI) in conjunction with isolation of the posterior left atrial wall (PVI+PWI) is associated with improved clinical outcomes in certain patients with atrial fibrillation (AF)., Objective: The purpose of this multicenter study was to evaluate the acute and long-term outcomes of PVI+PWI vs PVI alone performed using cryoballoon ablation in patients with persistent AF (persAF)., Methods: We examined the procedural safety and efficacy and short- and long-term outcomes in 390 consecutive patients with persAF who underwent a first-time cryoballoon ablation procedure using PVI+PWI (n = 222 [56.9%]) vs PVI alone (n = 168 [43.1%])., Results: Acute isolation was achieved in 99.7% of all pulmonary veins (PVI+PWI = 99.8% vs PVI alone = 99.3%; P = .23) using 6.3 ± 1.4 applications and 17 ± 2 minutes of cryoablation. PWI was achieved using 13.7 ± 3.2 applications and 34 ± 10 minutes of cryoablation. Adjunct radiofrequency ablation was required in 1.8% of patients to complete PVI (4 ± 2 minutes) and in 32.4% to complete PWI (5 ± 2 minutes). PVI+PWI yielded significantly greater posterior wall (77.2% ± 6.4% vs 40.6% ± 4.9%; P < .001) and total left atrial (53.3% ± 4.2% vs 36.3% ± 3.8%; P < .001) isolation. In addition, PVI+PWI was associated with greater AF termination (19.8% vs 8.9%; P = .003) and conversion to atrial flutters (12.2% vs 5.4%; P = .02). Adverse events were similar in both groups, whereas recurrence of AF and all atrial arrhythmias was lower with PVI+PWI at 12 months of follow-up. Moreover, in a Cox regression analysis, PVI+PWI emerged as a significant predictor of freedom from recurrent atrial arrhythmias (hazard ratio: 2.04; 95% confidence interval: 1.15-3.61; P = .015)., Conclusion: PVI+PWI can be achieved safely and effectively using the cryoballoon. This approach appears superior to PVI alone in patients with persAF., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objective: We explore whether a knowledge-discovery approach building a Classification and Regression Tree (CART) prediction model for weight loss (WL) in head and neck cancer (HNC) patients treated with radiation therapy (RT) is feasible., Methods and Materials: HNC patients from 2007 to 2015 were identified from a prospectively collected database Oncospace. Two prediction models at different time points were developed to predict weight loss ≥5 kg at 3 months post-RT by CART algorithm: (1) during RT planning using patient demographic, delineated dose data, planning target volume-organs at risk shape relationships data and (2) at the end of treatment (EOT) using additional on-treatment toxicities and quality of life data., Results: Among 391 patients identified, WL predictors during RT planning were International Classification of Diseases diagnosis; dose to masticatory and superior constrictor muscles, larynx, and parotid; and age. At EOT, patient-reported oral intake, diagnosis, N stage, nausea, pain, dose to larynx, parotid, and low-dose planning target volume-larynx distance were significant predictive factors. The area under the curve during RT and EOT was 0.773 and 0.821, respectively., Conclusions: We demonstrate the feasibility and potential value of an informatics infrastructure that has facilitated insight into the prediction of WL using the CART algorithm. The prediction accuracy significantly improved with the inclusion of additional treatment-related data and has the potential to be leveraged as a strategy to develop a learning health system.

Introduction: There is a paucity of data in favor of mechanical support during catheter ablation of ventricular tachycardia (VT). This study investigated the outcomes of VT ablation associated with mechanical support using percutaneous ventricular assist device (PVAD) versus intra-aortic balloon pump (IABP)., Methods and Results: We retrospectively examined the outcomes of patients who underwent VT ablation associated with PVAD versus IABP from 2010 to 2013, captured by the Medicare Inpatient Standard Analytic File database. Data from 345 patients (PVAD = 230, IABP = 115) were examined. On admission, the incidence of heart failure was higher in PVAD (84.3% vs. 73.0%; P = 0.01) with similar rates of renal failure in PVAD versus IABP (33.0% vs. 37.4%; P = 0.42). However, PVAD was associated with reduced in-hospital cardiogenic shock (9.1% vs. 23.5%; P  <  0.001), renal failure (11.7% vs. 21.7%; P = 0.01), and length of stay (8.4 ± 7.9 vs. 10.6 ± 7.5; P < 0.001), but with greater hospital discharges to home/self-care (66.0% vs. 51.6%; P = 0.02). Index mortality (6.5% vs. 19.1%; P = 0.001) and mortality in patients with cardiogenic shock (18.2% vs. 41.2%; P = 0.03) were significantly lower with PVAD versus IABP. Furthermore, PVAD was associated with lower all-cause (27.0% vs. 38.7%; P = 0.04) and heart failure-related (21.4% vs. 33.3%; P = 0.03) 30-day hospital readmissions, but with similar redo-VT ablation rates at 1 year (10.2% vs. 14.0%; P = 0.34)., Conclusion: Among the cases captured by the Medicare database, catheter ablation of VT associated with mechanical support using PVAD was associated with reduced in-hospital cardiogenic shock, renal failure, length of stay, hospital readmissions and mortality, but no difference in redo-VT ablation at 1 year., (© 2017 Wiley Periodicals, Inc.)

During chemical transmission, the function of synaptic proteins must be coordinated to efficiently release neurotransmitter. Synaptotagmin 2, the Ca2+ sensor for fast, synchronized neurotransmitter release at the human neuromuscular junction, has recently been implicated in a dominantly inherited congenital myasthenic syndrome associated with a non-progressive motor neuropathy. In one family, a proline residue within the C2B Ca2+-binding pocket of synaptotagmin is replaced by a leucine. The functional significance of this residue has not been investigated previously. Here we show that in silico modeling predicts disruption of the C2B Ca2+-binding pocket, and we examine the in vivo effects of the homologous mutation in Drosophila. When expressed in the absence of native synaptotagmin, this mutation is lethal, demonstrating for the first time that this residue plays a critical role in synaptotagmin function. To achieve expression similar to human patients, the mutation is expressed in flies carrying one copy of the wild type synaptotagmin gene. We now show that Drosophila carrying this mutation developed neurological and behavioral manifestations similar to those of human patients and provide insight into the mechanisms underlying these deficits. Our Drosophila studies support a role for this synaptotagmin point mutation in disease etiology.

Background: There are no recommendations on the optimal dosing for cryoablation of atrial fibrillation (Cryo-AF)., Objective: The purpose of this study was to develop and prospectively test a Cryo-AF dosing protocol guided exclusively by time-to-pulmonary vein (PV) isolation (TT-PVI) in patients undergoing a first-time Cryo-AF., Methods: In this multicenter study, we examined the acute/long-term safety/efficacy of Cryo-AF using the proposed dosing algorithm (Cryo-AF Dosing ; n = 355) against a conventional, nonstandardized approach (Cryo-AF Conventional ; n = 400) in a nonrandomized fashion., Results: Acute PV isolation was achieved in 98.9% of patients in Cryo-AF Dosing (TT-PVI = 48 ± 16 seconds) vs 97.2% in Cryo-AF Conventional (P = .18). Cryo-AF Dosing was associated with shorter (149 ± 34 seconds vs 226 ± 46 seconds; P <.001) and fewer (1.7 ± 0.8 vs 2.9 ± 0.8; P <.001) cryoapplications, reduced overall ablation (16 ± 5 minutes vs 40 ± 14 minutes; P <.001), fluoroscopy time (13 ± 6 minutes vs 29 ± 13 minutes; P <.001), left atrial dwell time (51 ± 14 minutes vs 118 ± 25 minutes; P <.001), and total procedure time (84 ± 23 minutes vs 145 ± 49 minutes; P <.001) but similar nadir balloon temperature (-47°C ± 8°C vs -48°C ± 6°C; P = .41) and total thaw time (43 ± 27 seconds vs 45 ± 19 seconds; P = .09) as compared to Cryo-AF Conventional . Adverse events (2.0% vs 2.7%; P = .48), including persistent phrenic nerve palsy (0.6% vs 1.2%; P = .33) and 12-month freedom from all atrial arrhythmias (82.5% vs 78.3%; P = .14), were similar between Cryo-AF Dosing and Cryo-AF Conventional . However, Cryo-AF Dosing was specifically associated with fewer atypical atrial flutters/tachycardias during long-term follow-up (8.5% vs 13.5%; P = .02) as well as fewer late PV reconnections at redo procedures (5.0% vs 18.5%; P <.001)., Conclusion: A novel Cryo-AF dosing algorithm guided by TT-PVI can help individualize the ablation strategy and yield improved procedural endpoints and efficiency as compared to a conventional, nonstandardized approach., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Limited data exist on cryoablation of atrial fibrillation (Cryo-AF) using the newly available third-generation (Arctic Front Advance-Short Tip [AFA-ST]) cryoballoon., Objective: In this multicenter study, we evaluated the safety and efficacy of Cryo-AF using the AFA-ST vs the second-generation (Arctic Front Advance [AFA]) cryoballoon., Methods: We examined the procedural safety and efficacy and the short- and long-term clinical outcomes associated with a first-time Cryo-AF performed in 355 consecutive patients (254/355 [72%] with paroxysmal AF), using either the AFA-ST (n = 102) or the AFA (n = 253) cryoballoon catheters., Results: Acute isolation was achieved in 99.6% of all pulmonary veins (PVs) (AFA-ST: 100% vs AFA: 99.4%; P = .920). Time to pulmonary vein isolation was recorded in 89.2% of PVs using AFA-ST vs 60.2% using AFA (P < .001). PVs targeted using AFA-ST required fewer applications (1.6 ± 0.8 vs 1.7 ± 0.8; P = .023), whereas there were no differences in the balloon nadir temperature (AFA-ST: -47.0°C ± 7.3°C vs AFA: -47.5°C ± 7.8°C; P = .120) or thaw time (AFA-ST: 41 ± 24 seconds vs AFA: 44 ± 28 seconds; P = .056). However, AFA-ST was associated with shorter left atrial dwell time (43 ± 5 minutes vs 53 ± 16 minutes; P < .001) and procedure time (71 ± 11 minutes vs 89 ± 25 minutes; P < .001). Furthermore, Cryo-AF using AFA-ST was completed more frequently by "single-shot" PV ablation (27.4% vs 20.2%; P = .031). Persistent phrenic nerve palsy (AFA-ST: 0% vs AFA: 0.8%; P = .507) and procedure-related adverse events (AFA-ST: 1.0% vs AFA: 1.6%; P = .554) were similar, as was the freedom from recurrent atrial arrhythmias at 10 months of follow-up (AFA-ST: 81.8% vs AFA: 79.9%; P = .658)., Conclusion: Cryo-AF using the AFA-ST cryoballoon offers an enhanced ability to assess time to pulmonary vein isolation, allowing for fewer cryoapplications and shorter left atrial dwell time and procedure time. Consequently, this allowed for procedural completion more frequently using a "single-shot" PV ablation with equivalent safety and efficacy., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Catheter ablation of atrial fibrillation (CAAF) using the cryoballoon has emerged as an alternate strategy to point-by-point radiofrequency. However, there is little comparative data on long-term durability of pulmonary vein (PV) isolation comparing these two modalities., Methods: In this multicenter, retrospective analysis, the incidences/patterns of late PV reconnection following an index CAAF using the second-generation cryoballoon versus open-irrigated, non-force-sensing radiofrequency were examined., Results: Of the 2002 patients who underwent a first-time CAAF, 186/1126 patients (16.5 %) ablated using cryoballoon and 174/876 patients (19.9 %) with non-contact force-guided radiofrequency required a repeat procedure at 11 ± 5 months. During follow-up, the incidence of atrial flutters/tachycardias was lower (19.9 vs. 32.8 %; p = 0.005) and fewer patients exhibited PV reconnection (47.3 vs. 60.9 %; p = 0.007) with cryoballoon versus radiofrequency. Additionally, fewer PVs had reconnected with cryoballoon versus radiofrequency (18.8 vs. 34.6 %; p < 0.001). With cryoballoon, the right inferior (p < 0.001) and left common (p = 0.039) PVs were more likely to exhibit late reconnection, versus the left superior PV with radiofrequency (p = 0.012). However, when comparing the two strategies, the left common PV was more likely to exhibit reconnection with cryoballoon, whereas all other PVs with the exception of the right inferior PV demonstrated a lower reconnection rate with cryoballoon versus radiofrequency. Lastly, in a logistic regression multivariate analysis, cryoballoon ablation and PV ablation time emerged as significant predictors of durable PV isolation at repeat procedure., Conclusions: In this large multicenter, retrospective analysis, CAAF using the second-generation cryoballoon was associated with improved durability of PV isolation compared to open-irrigated, non-force-sensing radiofrequency.

Background: The optimal irrigation flow rate (IFR) during epicardial radiofrequency (RF) ablation has not been established., Objective: This study specifically examined the impact of IFR and intrapericardial fluid (IPF) accumulation during epicardial RF ablation., Methods: Altogether, 452 ex vivo RF applications (10 g for 60 seconds) delivered to the epicardial surface of bovine myocardium using 3 open-irrigated ablation catheters (ThermoCool SmartTouch, ThermoCool SmartTouch-SF, and FlexAbility) and 50 in vivo RF applications delivered (ThermoCool SmartTouch-SF) in 4 healthy adult swine in the presence or absence of IPF were examined. Ex vivo, RF was delivered at low (≤3 mL/min), reduced (5-7 mL/min), and high (≥10 mL/min) IFRs using intermediate (25-35 W) and high (35-45 W) power. In vivo, applications were delivered (at 9.3 ± 2.2 g for 60 seconds at 39 W) using reduced (5 mL/min) and high (15 mL/min) IFRs., Results: Ex vivo, surface lesion diameter inversely correlated with IFR, whereas maximum lesion diameter and depth did not differ. While steam pops occurred more frequently at low IFR using high power (ThermoCool SmartTouch and ThermoCool SmartTouch-SF), tissue disruption was rare and did not vary with IFR. In vivo, charring/steam pop was not detected. Although there were no discernible differences in lesion size with IFR, surface lesion diameter, maximum diameter, depth, and volume were all smaller in the presence of IPF at both IFRs., Conclusion: Cooled-tip epicardial RF ablation created using reduced IFRs (5-7 mL/min) yields lesion sizes similar to those created using high IFRs (≥10 mL/min) without an increase in steam pop/tissue disruption, whereas the presence of IPF significantly reduces the lesion size., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: There is a paucity of data on the mechanisms of cough and hemoptysis that sometimes ensue from cryoballoon ablation of pulmonary veins (Cryo-PV). This study specifically examined the impact of ultra-cold (≤-60 °C, 3 minutes), prolonged (>-55 °C, 6 minutes), and conventional (>-55 °C, 3 minutes) Cryo-PV on lung/bronchial injury., Methods and Results: Four healthy adult swine underwent Cryo-PV. Each animal received Cryo-PV to the inferior common trunk and the right superior PV. In 2 animals, 1 PV was treated with 2 ultra-cold (Cryo-AUltra-cold ) and the other with 2 conventional (Cryo-AConventional ) cryoapplications. In the other 2 animals, 1 PV was ablated using 2 prolonged (Cryo-BProlonged ) and the other with 2 conventional (Cryo-BConventional ) applications. The nadir cryoballoon temperatures were lower in Cryo-AUltra-cold versus Cryo-AConventional (-66 ± 6 °C vs. -45 ± 5 °C; P = 0.001), but did not differ between Cryo-BProlonged and Cryo-BConventional (-46 ± 3 °C vs. -49 ± 3 °C; P = 0.123). Post-ablation bronchoscopy revealed immediate mucosal edema and erythema with/without bleeding in the adjacent bronchi in 100% of Cryo-AUltra-cold and 50% of Cryo-AConventional /Cryo-BConventional and Cryo-BProlonged . At 4 hours post-ablation, there were marked increases in bronchoalveolar macrophages (P <0.001), lymphocytes (P = 0.035) and neutrophils (P = 0.001). Furthermore, Cryo-AUltra-cold yielded the largest increase in the macrophage (P = 0.005) and neutrophil (P = 0.034) cell counts. While similar trends were seen in Cryo-BProlonged , these did not reach statistical significance., Conclusion: Cryo-PV can elicit acute bronchial inflammation, bleeding, and mucosal injury. While this was further augmented by ultra-cold cryoapplications, it was also evident to a lesser degree with prolonged and even conventional cryoapplications. The mechanism for this appears to be direct collateral injury., (© 2016 Wiley Periodicals, Inc.)

Background: Limited data exist on procedural and biophysical indicators of pulmonary vein (PV) isolation durability after the cryoballoon ablation of atrial fibrillation (AF)., Objective: The aim of this study was to investigate the procedural and biophysical characteristics associated with late PV reconnection (PVR) and durable PV isolation (PVI) after cryoablation using the currently available second-generation cryoballoon., Methods: Data from 435 PVs targeted in 112 consecutive patients who underwent a repeat procedure 14 ± 3 months after an index cryoablation of AF were examined., Results: Altogether, 111 PVs (25.5%) in 71 patients (63.4%) demonstrated PVR, whereas 324 PVs (74.5%) exhibited PVI. The number and duration of cryoballoon applications did not differ between PVR and PVI. However, the time to PV isolation (time to effect) was considerably shorter (39.1 ± 11.7 seconds vs 67.6 ± 19.7 seconds; P < .001), the balloon temperature at time to effect was significantly warmer (-32.1°C ± 7.8°C vs -39.4°C ± 5.8°C; P < .001), the balloon nadir temperature was slightly cooler (-48.7°C ± 4.6°C vs -47.8°C ± 2.9°C; P = .034), and the total thaw time (56.5 ± 25.4 seconds vs 34.8 ± 9.1 seconds; P < .001) and interval thaw times at 0°C (iTT0; 14.8 ± 10.9 seconds vs 7.1 ± 2.0 seconds; P < .001) and 15°C (54.2 ± 25.4 seconds vs 33.3 ± 9.1 seconds; P < .001) were notably longer with PVI than with PVR. However, only a time to effect of ≤60 seconds and an iTT0 of ≥10 seconds emerged as significant predictors of PV isolation durability. Consequently, in a multivariate model, presence of both criteria predicted <1% and their mere absence ~75% likelihood of PVR., Conclusion: A time to effect of ≤60 seconds and an iTT0 of ≥10 seconds significantly predict PV isolation durability after the cryoballoon ablation of AF. If both criteria are met, the likelihood of PV reconnection may be exceedingly low., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Over the last decade, cryoballoon ablation has emerged as an effective alternate strategy to point-by-point radiofrequency ablation for treatment of symptomatic atrial fibrillation. There are several reasons for this. First, the acute and long-term safety and efficacy associated with cryoablation appear comparable to that of radiofrequency ablation in patients with both paroxysmal and also persistent atrial fibrillation. Second, cryoablation offers certain advantages over conventional radiofrequency ablation including a gentler learning curve, shorter ablation and procedure times as well as lack of need for costly electroanatomical mapping technologies commonly utilized with radiofrequency ablation. Lastly, with the recent advent of the second-generation cryoballoon, the effectiveness of cryoablation has further improved dramatically. This comprehensive review examines the gradual evolution of the cryoablation tools as well as the rationale and data in support of the currently-available cryoballoon technologies for catheter ablation of atrial fibrillation.

Introduction: There are limited comparative data on catheter ablation of atrial fibrillation (CAAF) using the second-generation cryoballoon (CB-2) versus point-by-point radiofrequency (RF). This study examines the acute/long-term CAAF outcomes using these 2 strategies., Methods and Results: In this multicenter, retrospective, nonrandomized analysis, procedural and clinical outcomes of 1,196 patients (76% with paroxysmal AF) undergoing CAAF using CB-2 (n = 773) and open-irrigated, non-force sensing RF (n = 423) were evaluated. Pulmonary vein isolation was achieved in 98% with CB-2 and 99% with RF (P = 0.168). CB-2 was associated with shorter ablation time (40 ± 14 min vs. 66 ± 26 min; P < 0.001) and procedure time (145 ± 49 minutes vs. 188 ± 42 minutes; P < 0.001), but greater fluoroscopic utilization (29 ± 13 minutes vs. 23 ± 14 minutes; P < 0.001). While transient (7.6% vs. 0%; P < 0.001) and persistent (1.2% vs. 0%; P = 0.026) phrenic nerve palsy occurred exclusively with CB-2, other adverse event rates were similar between CB-2 (1.6%) and RF (2.6%); P = 0.207. However, freedom from AF/atrial flutter/tachycardia at 12 months following a single procedure without antiarrhythmic therapy was greater with CB-2 (76.6%) versus RF (60.4%); P < 0.001. While this difference was evident in patients with paroxysmal AF (P < 0.001), it did not reach significance in those with persistent AF (P = 0.089). Additionally, CB-2 was associated with reduced long-term need for antiarrhythmic therapy (16.7% vs. 22.0%; P = 0.024) and repeat ablations (14.6% vs. 24.1%; P < 0.001)., Conclusion: In this multicenter, retrospective, nonrandomized study, CAAF using CB-2 coupled with RF as occasionally required was associated with greater freedom from atrial arrhythmias at 12 months following a single procedure without antiarrhythmic therapy when compared to open-irrigated, non-force sensing RF, alone., (© 2015 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals, Inc.)

Background: Surgical exclusion of the left atrial appendage (LAA) can frequently yield incomplete closure., Objective: We evaluated the ischemic stroke/systemic embolization (SSE) risk in patients with atrial fibrillation (AF) and complete LAA closure (cLAA) vs incompletely surgically ligated LAA (ISLL) and LAA stump after surgical suture ligation., Methods: Seventy-two patients (CHA2DS2-VASc score 4.1 ± 1.9) underwent surgical LAA ligation in conjunction with mitral valve/AF surgery and postoperative LAA evaluation using computerized tomographic angiography., Results: Overall, cLAA was detected in 46 of 72 patients (64%), ISLL in 17 patients (24%), and LAA stump in 9 patients (12%). The incidences of oral anticoagulation (OAC) and recurrent AF were similar among the 3 groups during 44 ± 19 months of follow-up. SSE occurred in 2% of patients with cLAA vs 24% with ISLL and 0% with LAA stump (P = .006). None of the patients with SSE were receiving OAC, and all had recurrent AF during follow-up. Additionally, patients with SSE exhibited a significantly smaller ISLL neck diameter (2.8 ± 1.0 vs 7.1 ± 2.1 mm; P = .002). The annualized SSE risk was 1.9% (entire cohort), 6.5% (ISLL patients), 14.4% (ISLL patients not receiving OAC), and 19.0% (ISLL neck diameter ≤5.0 mm) per 100 patient-years of follow-up. The latter risk was nearly 5 times greater than predicted by conventional risk-stratification schemes. Moreover, ISLL emerged as an independent predictor of SSE in univariate analyses and as the sole predictor of SSE in a multivariate analysis., Conclusion: In patients with AF, ISLL is a predictor of SSE, independent of conventional risk stratification schemes. Consequently, OAC should be strongly considered in this high-risk cohort., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Sensory neurons provide important feedback to pattern-generating motor systems. In the crustacean stomatogastric nervous system (STNS), feedback from the anterior gastric receptor (AGR), a muscle receptor neuron, shapes the activity of motor circuits in the stomatogastric ganglion (STG) via polysynaptic pathways involving anterior ganglia. The AGR soma is located in the dorsal ventricular nerve posterior to the STG and it has been thought that its axon passes through the STG without making contacts. Using high-resolution confocal microscopy with dye-filled neurons, we show here that AGR from the crab Cancer borealis also has local projections within the STG and that these projections form candidate contact sites with STG motor neurons or with descending input fibers from other ganglia. We develop and exploit a new masking method that allows us to potentially separate presynaptic and postsynaptic staining of synaptic markers. The AGR processes in the STG show diversity in shape, number of branches and branching structure. The number of AGR projections in the STG ranges from one to three simple to multiply branched processes. The projections come in close contact with gastric motor neurons and descending neurons and may also be electrically coupled to other neurons of the STNS. Thus, in addition to well described long-loop pathways, it is possible that AGR is involved in integration and pattern regulation directly in the STG.

Otitis media (OM) is a polymicrobial disease wherein prior or concurrent infection with an upper respiratory tract virus plays an essential role, predisposing the middle ear to bacterial invasion. In episodes of acute bacterial OM, respiratory syncytial virus (RSV) is the most commonly isolated virus and thus serves as an important co-pathogen. Of the predominant bacterial agents of OM, the pathogenesis of disease due to Moraxella catarrhalis is the least well understood. Rigorous study of M. catarrhalis in the context of OM has been significantly hindered by lack of an animal model. To bridge this gap, we assessed whether co-infection of chinchillas with M. catarrhalis and RSV would facilitate ascension of M. catarrhalis from the nasopharynx into the middle ear. Chinchillas were challenged intranasally with M. catarrhalis followed 48 hours later by intranasal challenge with RSV. Within 7 days, 100% of nasopharynges were colonized with M. catarrhalis and homogenates of middle ear mucosa were also culture-positive. Moreover, within the middle ear space, the mucosa exhibited hemorrhagic foci, and a small volume of serosanguinous effusion was present in one of six ears. To improve upon this model, and based on epidemiologic data, nontypeable Haemophilus influenzae (NTHI) was included as an additional bacterial co-pathogen via intranasal administration four days before M. catarrhalis challenge. With this latter protocol, M. catarrhalis was cultured from the nasopharynx and middle ear homogenates of a maximum of 88% and 79% animals, respectively, for up to 17 days after intranasal challenge with M. catarrhalis. Additionally, hemorrhagic foci were observed in 79% of middle ears upon sacrifice. Thus, these data demonstrated that co-infection with RSV and NTHI predisposed to M. catarrhalis-induced ascending experimental OM. This model can be used both in studies of pathogenesis as well as to investigate strategies to prevent or treat OM due to M. catarrhalis.

In insects, a family of peptides with sequence homology to the vertebrate calcitonins has been implicated in the control of diuresis, a process that includes mixing of the hemolymph. Here, we show that a member of the insect calcitonin-like diuretic hormone (CLDH) family is present in the American lobster, Homarus americanus, serving, at least in part, as a powerful modulator of cardiac output. Specifically, during an ongoing EST project, a transcript encoding a putative H. americanus CLDH precursor was identified; a full-length cDNA was subsequently cloned. In silico analyses of the deduced prepro-hormone predicted the mature structure of the encoded CLDH to be GLDLGLGRGFSGSQAAKHLMGLAAANFAGGPamide (Homam-CLDH), which is identical to a known Tribolium castaneum peptide. RT-PCR tissue profiling suggests that Homam-CLDH is broadly distributed within the lobster nervous system, including the cardiac ganglion (CG), which controls the movement of the neurogenic heart. RT-PCR analysis conducted on pacemaker neuron- and motor neuron-specific cDNAs suggests that the motor neurons are the source of the CLDH message in the CG. Perfusion of Homam-CLDH through the isolated lobster heart produced dose-dependent increases in both contraction frequency and amplitude and a dose-dependent decrease in contraction duration, with threshold concentrations for all parameters in the range 10(-11) to 10(-10) mol l(-1) or less, among the lowest for any peptide on this system. This report is the first documentation of a decapod CLDH, the first demonstration of CLDH bioactivity outside the Insecta, and the first detection of an intrinsic neuropeptide transcript in the crustacean CG.

Primary care physicians have several external sources of information available when referring a patient to a specialist. The most-used sources were a fellow physician, followed by the specialist, the patient or the patient's family, and to a lesser extent, hospital-controlled sources including referral directories, call services, and sales representatives. The authors tested a cost-benefit model where source usage was predicted to increase as the costs of using the source decreased and benefits increased.

Health care organizations are beginning to use sales forces in much the same way as traditional for-profit organizations have used selling programs in the past. However, numerous challenges to the implementation of selling in the health care industry have yet to be overcome. The authors report viewpoints expressed by administrators in a national survey of health care organizations.

The authors report the state of the art of personal selling in health care organizations in the United States. The research was conducted through the use of a previously validated sales orientation index, administered to various types of health care organizations. The findings indicate that personal selling is far from being a fully integrated promotional tool in the health care industry. Differences in the sales orientation of health care organizations are found to be related to environmental and organizational factors.

Analysis of covariance structures (LISREL) was used to examine the influence of consumer held perceptions of service quality on consumer satisfaction and intentions to return. Results indicate that service quality is a significant predictor of consumer satisfaction which, in turn, predicts intention to return. Health care marketing implications are discussed.

Hospitals often have looked to industry as a source of solutions to business problems. In recent years, they have begun to adopt a concept that has been used by manufacturers for more than 50 years--product line management (PLM). One characteristic of PLM is the designation of a product champion whose responsibility it is to promote the product both inside and outside the organization as well as to view for organizational resources to support the product. This article presents the findings of an exploratory study that indicates that although many hospitals are successfully utilizing PLM, a number of barriers to the implementation of this concept remain.

Agents considered to alter cAMP accumulation in bone cells were evaluated for their effects on protein production and sugar incorporation by bone cells. Total protein production or mannose incorporation by cells and in media were measured by the amount of radioactivity incorporated into trichloroacetic-acid precipitable fractions. Incorporation of radioactive leucine into the cellular and secreted proteins was linear over 5 h; radioactive mannose incorporation was linear only up to 2 h. Cells were also incubated with selected agents and radioactive mannose or leucine for 2 h. Addition of parathyroid hormone (PTH), isoproterenol or dibutyryl cAMP to osteoblasts resulted in a significant increase in mannose incorporation; dibutyryl cGMP and butyric acid had no effect on mannose incorporation. None of the agents altered total protein production. Thus PTH stimulates mannose incorporation into osteoblasts and this effect is, at least in part, modulated by cAMP.

The secretion of three antimicrobial proteins from the parotid glands of 82 generally healthy men and women, 22 to 81 years in age, was examined. No change was observed in the levels of secretory IgA, but statistically significant, modest elevations (approximately 50 to 100%) of lactoferrin, in both unstimulated and stimulated secretions, and lysozyme, in unstimulated secretions, were detected when results were expressed as mg antimicrobial protein/100 ml saliva. However, these alterations were not observed if data were expressed as mg antimicrobial protein/g total protein. Also, no change was detected in an acinar cell exocrine product, the anionic proline-rich proteins, as reported previously by our laboratory. The data are consistent with a maintenance of protective functions in parotid saliva during aging.

Reduced adherence and aggregation were associated with protein alterations in parotid saliva after chronic treatment with the beta-adrenergic agonist isoproterenol. In contrast, saliva from animals treated with the beta-antagonist, propranolol, did not cause such changes; the protein composition of this saliva was similar to that of controls. SDS-polyacrylamide gel electrophoresis of protein in saliva samples before and after they were mixed with 10 mg of spheroidal hydroxyapatite beads (HA), as well as protein adsorbed and recovered from the HA, showed that an acidic, proline-rich protein with a molecular weight of approx. 40,000 was the predominant protein adsorbed. This protein was significantly diminished in saliva from isoproterenol-treated rats. Proteins with molecular weights between 44,000 and 48,000 and unique to the saliva from isoproterenol-treated animals were also adsorbed to HA. Thus alterations in proline-rich proteins of parotid saliva may influence the adherence and aggregation of oral bacteria, two processes considered important for in-vivo colonization of oral surfaces.

Hospitals tend to use an incomplete means of developing new services. The result is a lack of attention to the needs of the intended target markets. A model for developing new hospital services is suggested, one that allows greater input from the service recipients. An illustrative case is presented.

Studies employing the matrix-induced endochondral bone formation system have outlined the processes involved in bone induction. An initial event is increased migration of mesenchymal cells to the implant site prior to endochondral calcification. This suggests that chemotactic factors in the bone matrix may be involved in the osteogenic process. Extracts of human fetal bone, obtained by sequential demineralization, stimulated the migration of osteoblast-like cells in a dose-dependent fashion, as assayed in the Boyden chamber. In contrast, comparable extracts of normal adult bone (40-year-old male) did not stimulate osteoblast migration. Monocytes, potential osteoclast precursors, did not migrate in response to either of these extracts. These studies suggest that significant differences exist in protein composition and/or distribution between fetal and adult human bones. These differences may well influence the remodeling potential of these bones.