Collapse of late endosomal pH elicits a rapid Rab7 response via the V-ATPase and RILP.

Endosomal-lysosomal trafficking is accompanied by the acidification of endosomal compartments by the H+-V-ATPase to reach low lysosomal pH. Disruption of the correct pH impairs lysosomal function and the balance of protein synthesis and degradation (proteostasis). Here, we treated mammalian cells with the small dipeptide LLOMe, which is known to permeabilize lysosomal membranes, and find that LLOMe also impacts late endosomes (LEs) by neutralizing their pH without causing membrane permeabilization. We show that LLOMe leads to hyperactivation of Rab7 (herein referring to Rab7a), and disruption of tubulation and mannose-6-phosphate receptor (CI-M6PR; also known as IGF2R) recycling on pH-neutralized LEs. pH neutralization (NH4Cl) and expression of Rab7 hyperactive mutants alone can both phenocopy the alterations in tubulation and CI-M6PR trafficking. Mechanistically, pH neutralization increases the assembly of the V1G1 subunit (encoded by ATP6V1G1) of the V-ATPase on endosomal membranes, which stabilizes GTP-bound Rab7 via RILP, a known interactor of Rab7 and V1G1. We propose a novel pathway by which V-ATPase and RILP modulate LE pH and Rab7 activation in concert. This pathway might broadly contribute to pH control during physiologic endosomal maturation or starvation and during pathologic pH neutralization, which occurs via lysosomotropic compounds and in disease states.

Use of perceptual memory as a performance validity indicator: initial validation with simulated mild traumatic brain injury.

INTRODUCTION: Many commonly employed performance validity tests (PVTs) are several decades old and vulnerable to compromise, leading to a need for novel instruments. Because implicit/non-declarative memory may be robust to brain damage, tasks that rely upon such memory may serve as an effective PVT. Using a simulation design, this experiment evaluated whether novel tasks that rely upon perceptual memory hold promise as PVTs. METHOD: Sixty healthy participants were provided instructions to simulate symptoms of mild traumatic brain injury (TBI), and they were compared to a group of 20 honest responding individuals. Simulator groups received varying levels of information concerning TBI symptoms, resulting in naïve, sophisticated, and test-coached groups. The Word Memory Test, Test of Memory Malingering, and California Verbal Learning Test-II Forced Choice Recognition Test were administered. To assess perceptual memory, selected images from the Gollin Incomplete Figures and Mooney Closure Test were presented as visual perception tasks. After brief delays, memory for the images was assessed. RESULTS: No group differences emerged on the perception trials of the Gollin and Mooney figures, but simulators remembered fewer images than the honest responders. Simulator groups differed on the standard PVTs, but they performed equivalently on the Gollin and Mooney figures, implying robustness to coaching. Relying upon a criterion of 90% specificity, the Gollin and Mooney figures achieved at least 90% sensitivity, comparing favorably to the standard PVTs. CONCLUSIONS: The Gollin and Mooney figures hold promise as novel PVTs. As perceptual memory tests, they may be relatively robust to brain damage, but future research involving clinical samples is necessary to substantiate this assertion.

Morphodynamics of a composite sand-cobble beach in response to extratropical cyclone Fiona and seasonal wave variability.

Climate change is driving higher coastal water levels, and models project accelerated future sea-level rise and coastal storm intensification. These dynamics paired with anthropogenic coastal alterations will drive drastic coastal change worldwide. Composite beaches with mixed sediment sizes warrant detailed study as these exhibit complex morphodynamics in response to changing hydrodynamics due to the distinct transport thresholds of different sediment types. This study uses a novel multi-method approach to investigate a composite sand-cobble beach in Atlantic Canada experiencing a shortening seasonal sand-covered period. Hydrodynamic forcing and associated beach changes were monitored over a focused eight-month period, while satellite-based visual imagery and reconstructed wave data were analyzed over longer periods. Results show that intra-annual wave energy changes drive sand dynamics, with reduced summer wave energy facilitating short-term deposition. Long-term positive trends were identified in late spring wave heights, which likely contribute to the shortening sand-covered period. Seasonal dynamics were overwhelmed by extratropical cyclone Fiona, which made landfall on September 24, 2022, generating significant wave heights up to 6.8 m in the bay, mobilizing sediment, and steepening cobble berms. A new index approach based on visual imagery facilitated the investigation of beach sand appearance/disappearance using the relative redness of sand compared to cobble. Finally, the UAV-based surveys yielded high-resolution orthomosaics and LiDAR-based elevation mapping, and highlighted pronounced longshore variability in erosion and deposition during Fiona. The beach mostly recovered to pre-storm conditions in <4 months, which indicates that proposed beach nourishment activities may only experience temporary success. The longer-term results showing a conversion of sand to cobble suggest that loss of sandy beach habitat is likely to increase, even without shoreline migration or coastal squeeze driven by sea-level rise.

Regulation of Endosomal Trafficking by Rab7 and Its Effectors in Neurons: Clues from Charcot-Marie-Tooth 2B Disease.

Intracellular endosomal trafficking controls the balance between protein degradation and synthesis, i.e., proteostasis, but also many of the cellular signaling pathways that emanate from activated growth factor receptors after endocytosis. Endosomal trafficking, sorting, and motility are coordinated by the activity of small GTPases, including Rab proteins, whose function as molecular switches direct activity at endosomal membranes through effector proteins. Rab7 is particularly important in the coordination of the degradative functions of the pathway. Rab7 effectors control endosomal maturation and the properties of late endosomal and lysosomal compartments, such as coordination of recycling, motility, and fusion with downstream compartments. The spatiotemporal regulation of endosomal receptor trafficking is particularly challenging in neurons because of their enormous size, their distinct intracellular domains with unique requirements (dendrites vs. axons), and their long lifespans as postmitotic, differentiated cells. In Charcot-Marie-Tooth 2B disease (CMT2B), familial missense mutations in Rab7 cause alterations in GTPase cycling and trafficking, leading to an ulcero-mutilating peripheral neuropathy. The prevailing hypothesis to account for CMT2B pathologies is that CMT2B-associated Rab7 alleles alter endocytic trafficking of the neurotrophin NGF and its receptor TrkA and, thereby, disrupt normal trophic signaling in the peripheral nervous system, but other Rab7-dependent pathways are also impacted. Here, using TrkA as a prototypical endocytic cargo, we review physiologic Rab7 effector interactions and control in neurons. Since neurons are among the largest cells in the body, we place particular emphasis on the temporal and spatial regulation of endosomal sorting and trafficking in neuronal processes. We further discuss the current findings in CMT2B mutant Rab7 models, the impact of mutations on effector interactions or balance, and how this dysregulation may confer disease.

Endosomal Transport to Lysosomes and the Trans-Golgi Network in Neurons and Other Cells: Visualizing Maturational Flux.

High-level microscopy enables the comprehensive study of dynamic intracellular processes. Here we describe a toolkit of combinatorial approaches for fixed cell imaging and live cell imaging to investigate the interactions along the trans-Golgi network (TGN)-endosome-lysosome transport axis, which underlie the maturation of endosomal compartments and degradative flux. For fixed cell approaches, we specifically highlight how choices of permeabilization conditions, antibody selection, and antibody multiplexing affect interpretation of results. For live cell approaches, we emphasize the use of sensors that read out pH and degradative capacity in combination with endosomal identity for elucidating dynamic compartment changes.

Classification accuracy of the word memory test genuine memory impairment index.

OBJECTIVE: The Word Memory Test (WMT) assesses non-credible performance in neuropsychological assessment. To mitigate risk of false positives among patients with severe cognitive dysfunction, the Genuine Memory Impairment Profile was derived. Only a modest number of investigations has evaluated classification accuracy among clinical samples, leaving the GMIP's accuracy largely uncertain. Accordingly, a simulation experiment evaluated the classification accuracy of the GMIP in a group of healthy individuals coached to simulate mild traumatic brain injury (TBI) related memory impairment on the WMT. PARTICIPANTS AND METHODS: Eighty healthy individuals were randomly assigned to one of the four experimental groups. One group was provided superficial information concerning TBI symptoms (naïve simulators), another was provided extensive information concerning TBI symptoms (sophisticated simulators), and a third group was provided extensive TBI symptom information and tactics to evade detection by performance validity tests (PVT) (test-coached). An honest responding control group was directed to give their best performance. All participants were administered the California Verbal Learning Test-2 (CVLT-2) and the WMT. RESULTS: Among the TBI simulators, 90% of the test-coached, 95% of the sophisticated simulators, and 100% of the naïve simulators were correctly classified as exaggerating memory impairment on the primary WMT indices. The simulator groups performed worse than the honest responding group on the CVLT-2. Of those who exceeded the WMT cutoffs, 60%, 27%, and 6% of the naïve-, sophisticated-, and test-coached simulators manifested the GMIP profile, respectively. CONCLUSIONS: The GMIP is apt to misclassify individuals as having genuine memory impairment, especially if a naïve or unsophisticated effort is made to exert non-credible performance. Indeed, individuals who employ the least sophisticated efforts to exaggerate cognitive impairment appear most likely to manifest the GMIP. The GMIP should be used cautiously to discriminate genuine impairment from non-credible performance, especially among people with mild TBI.

Computed Tomography and Magnetic Resonance Imaging are Similarly Reliable in the Assessment of Glenohumeral Arthritis and Glenoid Version.

BACKGROUND: The purpose of this study was to compare the intraobserver and interobserver reliability of CT and T2-weighted MRI for evaluation of the severity of glenoid wear, glenohumeral subluxation, and glenoid version. METHODS: Sixty-one shoulders with primary osteoarthritis had CT and MRI scans before shoulder arthroplasty. All slices were blinded and randomized before evaluation. Two fellowship-trained shoulder surgeons and three orthopaedic surgery trainees reviewed the images to classify glenoid wear (Walch and Mayo classifications) and glenohumeral subluxation (Mayo classification). Glenoid version was measured using Friedman's technique. After a minimum two-week interval, the process was repeated. RESULTS: Intraobserver reliability was good for the CT group and fair-to-good for the MRI group for the Walch, Mayo glenoid, and Mayo subluxation classifications; interobserver reliability was poor for the CT and fair-to-poor for the MRI group. For the measurement of glenoid version, intraobserver reliability was good for the CT and substantial for the MRI group; interobserver agreement was good for both groups. There were no significant differences in reliability between staff surgeons and trainees for any of the classifications or measurements. CONCLUSION: CT and MRI appear similarly reliable for the classification of glenohumeral wear patterns. For the measurement of glenoid version, MRI was slightly more reliable than CT within observers. Differences in training level did not produce substantial differences in agreement, suggesting these systems can be applied by observers of different experience levels with similar reliability.

Memory in multiple sclerosis: A reappraisal using the item specific deficit approach.

OBJECTIVE: As many as 65% of people with multiple sclerosis (MS) have clinically significant memory impairment, but the nature of this deficit is controversial. Some investigations suggest that an inability to retrieve newly learned information from memory is prominent, whereas others imply that compromised acquisition accounts for impairment. Prior research has not simultaneously evaluated acquisition and retrieval processes in MS, and fewer have attempted to account for initial acquisition when studying retrieval. The Item Specific Deficit Approach (ISDA) offers a method of quantifying acquisition, retrieval, and retention processes, with the latter two mechanisms being adjusted for initial acquisition. To simultaneously quantify acquisition and retrieval abilities, the ISDA was applied to list learning performance in two independent samples of people with MS and corresponding healthy comparison groups. PARTICIPANTS AND METHODS: Study 1 included 85 people with MS and 47 healthy individuals. Study 2 involved a separate sample of 79 people with MS and 22 healthy people. They were administered neuropsychological batteries, and participants with MS were classified as globally impaired or unimpaired. The California Verbal Learning Test-II was administered to assess new-learning in both studies, and responses were scored using the ISDA. RESULTS: Both studies revealed that cognitively impaired people with MS manifest weaknesses involving acquisition and retrieval. Nearly identical effect sizes emerged across samples, with cognitive impairment achieving a medium effect upon acquisition and a large effect upon retrieval. CONCLUSIONS: These findings accord well with previous research showing diminished acquisition and retrieval among people with MS. The results may also reconcile contradictory findings in the extant literature by showing that memory impairment in MS is not exclusively attributable to either acquisition or retrieval. Rather, both processes may manifest across people with MS. The replication across samples with nearly identical effect sizes implies that these effects are reliable and possess external validity. These data hold implications for memory rehabilitation interventions involving people with MS, and suggest that acquisition and retrieval processes should be addressed in treatment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Effects of diminished positive mood and depressed mood upon verbal learning and memory among people with multiple sclerosis.

Objective: Cognitive impairment affects as many as 65% of people with multiple sclerosis (PWMS), and memory impairment confers greater severity of disability and functional impairment. Depression is also common among PWMS, and lifetime prevalence rates are as high as 50%. Research has yet to clearly define the relationship between memory dysfunction and depression among PWMS, and may reflect incomplete assessment of depressive symptoms. The present study examined different aspects of depressive symptoms including anhedonia (i.e., diminished positive mood) and their relationships with verbal learning and memory among PWMS.Method: Participants were 48 healthy individuals and 96 PWMS. They were primarily Caucasian (90.3%) and female (75.0%). Participants completed the California Verbal Learning Test-2 (CVLT-2) to assess verbal learning and memory and the Chicago Multiscale Depression inventory to assess depressed mood (CMDI-Mood) and diminished positive mood (CMDI-DPM).Results: Linear regression revealed that the main effect of CMDI-DPM and the interaction of CMDI-DPM and CMDI-Mood significantly explained variance across learning, recall, and recognition CVLT-2 indices. Follow-up analyses indicated that CMDI-DPM was only significant in the absence of high CMDI-Mood scores. CMDI-Mood explained variance in only CVLT-2 Trial B.Conclusions: Depressed mood had little direct effect upon memory performance in PWMS. In the absence of severe depressed mood, higher levels of positive mood corresponded to better memory performance. However, the impact of diminished positive mood was rendered null among those endorsing high levels of depressed mood. These data may imply that anhedonia corresponds with poorer memory function among PWMS, and suggests that investigators and clinicians should assess multiple mood dimensions among PWMS.

Performance of Radiomics derived morphological features for prediction of aneurysm rupture status.

BACKGROUND: Morphological differences between ruptured and unruptured cerebral aneurysms represent a focus of neuroimaging researchfor understanding the mechanisms of aneurysmal rupture. We evaluated the performance of Radiomics derived morphological features, recently proposed for rupture status classification, against automatically measured shape and size features previously established in the literature. METHODS: 353 aneurysms (123 ruptured) from three-dimensional rotational catheter angiography (3DRA) datasets were analyzed. Based on a literature review, 13 Radiomics and 13 established morphological descriptors were automatically extracted per aneurysm, and evaluated for rupture status prediction using univariate and multivariate statistical analysis, yielding an area under the curve (AUC) metric of the receiver operating characteristic. RESULTS: Validation of overlapping descriptors for size/volume using both methods were highly correlated (p<0.0001, R 2=0.99). Univariate analysis selected AspectRatio (p<0.0001, AUC=0.75), Non-sphericity Index (p<0.0001, AUC=0.75), Height/Width (p<0.0001, AUC=0.73), and SizeRatio (p<0.0001, AUC=0.73) as best among established descriptors, and Elongation (p<0.0001, AUC=0.71) and Flatness (p<0.0001, AUC=0.72) among Radiomics features. Radiomics Elongation correlated best with established Height/Width (R 2=0.52), whereas Radiomics Flatness correlated best with Ellipticity Index (R 2=0.54). Radiomics Sphericity correlated best with Undulation Index (R 2=0.65). Best Radiomics performers, Elongation and Flatness, were highly correlated descriptors (p<0.0001, R 2=0.75). In multivariate analysis, established descriptors (Height/Width, SizeRatio, Ellipticity Index; AUC=0.79) outperformed Radiomics features (Elongation, Maximum3Ddiameter; AUC=0.75). CONCLUSION: Although recently introduced Radiomics analysis for aneurysm shape and size evaluation has the advantage of being an efficient operator independent methodology, it currently offers inferior rupture status discriminant performance compared with established descriptors. Future research is needed to extend the current Radiomics feature set to better capture aneurysm shape information.

Increased focal internal carotid artery angulation in patients with posterior communicating artery aneurysms.

BACKGROUND: Aneurysms at the posterior communicating artery (PCOM) origin represent the most common location on the internal carotid artery (ICA), and are associated with greater recurrence following endovascular treatment. We evaluate the association between ICA angulation in three-dimensional (3D) space and PCOM aneurysmal development, using high-resolution 3D rotational angiography (3DRA) studies. METHODS: 3DRA datasets were evaluated in 70 patients with PCOM aneurysms, 31 non-aneurysmal contralateral, and 86 healthy controls (187 total). The local angle formed by upstream and downstream ICA segments at the PCOM origin, αICA@PCOM, was measured using 3DRA multiplanar reconstruction. Computational fluid dynamics (CFD) analysis was performed on parametric and patient-based models. RESULTS: αICA@PCOM was significantly larger in aneurysm-bearing ICA segments (68.14±11.91°) compared with non-aneurysmal contralateral (57.17±10.76°, p<0.001) and healthy controls (48.13±13.68°, p<0.001). A discriminant threshold αICA@PCOM value of 61° (87% specificity, 80% sensitivity) was established (area under the curve (AUC)=0.88). Ruptured PCOM aneurysms had a significantly larger αICA@PCOM compared to unruptured (72.65±15.16° vs 66.35±9.94°, p=0.04). In parametric and patient-based CFD analysis, a large αICA@PCOM induces high focal pressure at the PCOM origin, relatively low wall shear stress (WSS), and high proximal WSS spatial gradients (WSSG). CONCLUSION: ICA angulation at PCOM origin is significantly higher in vessels harboring PCOM aneurysms compared with contralateral and healthy ICAs. This sharper bend in the ICA leads to high focal pressure at the aneurysm neck, low focal WSS and high proximal WSSG. These findings underline the importance of morphological ICA variations and the likelihood of PCOM aneurysm, an association which can inform clinical decisions and may serve in predictive analytics.

Safety and Cost-Effectiveness of Outpatient Unicompartmental Knee Arthroplasty in the Ambulatory Surgery Center: A Matched Cohort Study.

Using an age- and comorbidity-matched cohort, we compared patients who underwent unicompartmental knee arthroplasty in an ambulatory surgery center with those who underwent the procedure in a traditional hospital inpatient setting. Postoperatively, the ambulatory surgery center cohort had fewer major complications than the inpatient cohort. No ambulatory surgery center patients required acute hospital admission and none had major complications. Four major complications occurred in the inpatient cohort. There was no difference in complication rates. Our results suggest that outpatient unicompartmental knee arthroplasty in a freestanding ambulatory surgery center is a safe and reasonable alternative to the traditional inpatient hospital setting.

Validity of the Verbal Concept Attainment Test in multiple sclerosis.

OBJECTIVE: As many as 70% of people with multiple sclerosis (MS) have clinically significant cognitive impairment, and most of these individuals exhibit executive dysfunction. Most research concerning executive dysfunction in MS has focused upon nonverbal measures. The Verbal Concept Attainment Test (VCAT) has demonstrated construct validity as an executive function measure in people infected with HIV and in people with focal brain lesions, but its validity among people with MS is unknown. The current study evaluated the VCAT's criterion, diagnostic, and ecological validity in people with MS. METHOD: A comprehensive neuropsychological battery was administered to 44 healthy individuals and 97 people with MS. Based on existing norms, they were classified as impaired or unimpaired, resulting in 65 people with MS categorized as unimpaired and 32 as impaired. They were administered a battery assessing neuropsychological impairment and disability status. RESULTS: The VCAT correlated with most measures of neuropsychological function, but its largest correlations occurred with measures of executive function, working memory, and verbal memory. Regarding classification accuracy, the VCAT achieved satisfactory sensitivity and specificity in identifying neuropsychological impairment in people with MS. The VCAT achieved moderate correlations with measures of disability status. CONCLUSIONS: The data provide evidence for an optimal VCAT cutoff score for establishing neuropsychological impairment in people with MS, and they demonstrate that the VCAT possesses acceptable criterion, diagnostic, and ecological validity. As such, these data support the inclusion of the VCAT in research and clinical practice involving people with MS.

Modelling the transport of shipborne per- and polyfluoroalkyl substances (PFAS) in the coastal environment.

Per- and polyfluoroalkyl substances (PFAS) are presently essential ingredients in aqueous film forming foam (AFFF) used for fire-fighting, but are also pervasive environmental contaminants. The use and subsequent release and transport of AFFF in the ocean environment from marine vessels has not been studied to date. A numerical model (Delft3D) was rigorously calibrated and validated for the hydrodynamics, and used to predict the transport of PFAS released instantaneously into a large harbour (Halifax Harbour, Nova Scotia) that is representative of coastal environments in eastern Canada and other parts of the world. The numerical model results indicate that PFAS released in the presence of strong winds and waves during a storm will travel up to 31 km in 2 days, approximately 40% farther than PFAS release during a time period dominated by tidal currents with light winds and small waves (<1 m). After a 10 day simulation, PFAS levels from release sites in the Inner Harbour were higher (40-60 µg/L) compared to PFAS levels from the Outer Harbour release site which had decreased to low levels (<1 µg/L) during a non-storm period. Along shorelines within the Harbour, PFAS concentrations remained elevated after 12 h (40-500 µg/L) and 48 h (2-300 µg/L). These concentrations are within the range of PFAS guidance values for recreational water use. The methods described here are relevant to studies of PFAS dispersion and transport in other coastal areas, and could be used to determine best practices for applications of AFFF in the coastal environment.

Preoperative Risk Factors for Complications in Elective Ankle and Hindfoot Reconstruction.

BACKGROUND: The purpose of this study was to examine medical, social, and psychological factors associated with complications and reoperation after foot and ankle reconstruction. METHODS: A retrospective chart review was conducted of 132 patients (135 feet; 139 operative cases) who had elective foot and ankle reconstruction. Medical, social, and psychological variables were documented. Primary outcomes included complications and reoperations. RESULTS: The overall complication rate was 28% (39/139), and the reoperation rate was 17% (24/139). Alcohol use (P = .03) and preoperative narcotic use (P = .02) were risk factors for complications, with delayed wound healing more frequent in alcohol users (P = .03) and deep infection (P = .045) and nonunion (P = .046) more frequent preoperative narcotic use. Deep infection also was more frequent in tobacco users (P < .01). Older patients were less likely to undergo reoperation (risk of reoperation increased with age). Other variables were not associated with increased complications. CONCLUSION: Patients who consumed alcohol or had been prescribed any amount of narcotic within 3 months preoperatively were at increased risk for complications. Patients who smoked were more likely to have a wound infection. Surgeons should be aware of these factors and counsel patients before surgery. LEVELS OF EVIDENCE: Level III: Retrospective comparative study.

Comparison of Posterior Approach With Intramedullary Nailing Versus Lateral Transfibular Approach With Fixed-Angle Plating for Tibiotalocalcaneal Arthrodesis.

BACKGROUND: A variety of operative approaches and fixation techniques have been described for tibiotalocalcaneal (TTC) arthrodesis. The intramedullary (IM) nail and lateral, fixed-angle plating are commonly used because of ease of use and favorable biomechanical properties. A lateral, transfibular (LTF) approach allows for direct access to the tibiotalar and subtalar joints, but the posterior, Achilles tendon-splitting (PATS) approach offers a robust soft tissue envelope. The purpose of this study was to compare the results of TTC arthrodesis with either a PATS approach with IM nailing or LTF approach with fixed-angle plating. METHODS: A retrospective review was performed on all patients who underwent simultaneous TTC arthrodesis with minimum 1 year clinical and radiographic follow up. Patients were excluded if they underwent TTC arthrodesis through an approach other than PATS or LTF, and received fixation without an IM nail or fixed-angle plate. Primary outcomes examined were union rate, revisions, and complications. Thirty-eight patients underwent TTC arthrodesis with a PATS approach and IM nailing, and 28 with a LTF approach and lateral plating. RESULTS: The overall union rate was 71%; 76% (29 of 38 patients) for the PATS/IM nail group, and 64% (18 of 28) for LTF/plating group ( P = .41). Symptomatic nonunion requiring revision arthrodesis occurred in 16% (6 of 38) of the PATS/IM nail group versus 7% (2 of 28) in the LTF/lateral plating group ( P = .45). There were no significant differences in individual tibiotalar or subtalar union rates, superficial wound problems, infection, symptomatic hardware, stress fractures, or nerve irritations. CONCLUSION: Union, revision, and complication rates were similar for TTC arthrodesis performed with a PATS approach and IM nail compared with an LTF approach and fixed-angle plate in a complex patient population. Both techniques were adequate, especially when prior incisions, preexisting hardware, or deformity preclude options. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Liposomal Bupivacaine Versus Continuous Popliteal Sciatic Nerve Block in Total Ankle Arthroplasty.

BACKGROUND: Liposomal bupivacaine (LB) is widely used in joint arthroplasty, but there is little reported on the use of LB in foot and ankle surgery. Continuous popliteal sciatic nerve block (CPSNB) is more commonly used for major foot and ankle reconstructions. The purpose of this study was to compare use of intraoperative LB injection to CPSNB as a regional anesthetic for total ankle arthroplasty (TAA), with attention to postoperative pain scores, narcotic use, and complications. METHODS: Retrospective review of TAA patients of 2 fellowship-trained orthopedic foot and ankle surgeons was performed. Patients received either preoperative single-shot popliteal sciatic nerve block with 0.2% ropivacaine followed by intraoperative injection of LB or preoperative CPSNB alone. Outcomes examined were visual analog scale (VAS) pain score at 8 hours, 24 hours, 1 week, and 3 weeks following surgery; need for opioid pain medication refill; physician office notification for pain issues or other adverse events; and complications within the first 90 days following surgery. Standard statistical analysis was performed, and P < .05 was considered significant. Seventy-five patients were identified who underwent TAA and met inclusion criteria. Forty-one received LB, and 34 received CPSNB. RESULTS: No statistical difference was seen between groups with regard to complications, emergency department visits, readmissions, reoperations, VAS pain score at any time point, physician office contacts, and narcotic refills. Sixteen of 41 (39%) LB patients had narcotic refills, versus 12 of 34 (35%) CPSNB patients ( P = .81). Two of 41 (5%) LB patients had a complication postoperatively, versus 4 of 34 (12%) CPSNB patients. There were no complications specific to the anesthetic used in either group. CONCLUSION: This is the first study evaluating the use of LB for total ankle arthroplasty. Liposomal bupivacaine was safe and effective as an option for regional anesthetic and postoperative pain control, with comparable results to CPSNB. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Safety of Outpatient Total Ankle Arthroplasty vs Traditional Inpatient Admission or Overnight Observation.

BACKGROUND: Total joint surgeons have successfully performed hip, knee, and shoulder arthroplasty procedures in the outpatient setting without compromising safety, satisfaction, or results. The purpose of this study was to evaluate outpatient total ankle arthroplasty (TAA) as compared with overnight or extended inpatient stay, with regard to 90-day medical and operative complications, reoperations, readmissions or emergency room visits, and pain control. METHODS: The medical records of patients who underwent TAA with 1 fellowship-trained orthopedic foot and ankle surgeon were reviewed. Outcome measures included operative complications, adverse medical events, readmission or emergency room visit for any reason, or reoperation within 90 days following surgery; surgeon's office contact before first postoperative visit regarding pain or other issues; visual analog scale pain score at the first postoperative visit; and need for narcotic refill. Outcomes were assessed by admission status: outpatient, overnight observation, or inpatient admission. Standard statistical analysis was used, and P < .05 was considered significant. RESULTS: Eighty-one patients underwent TAA who met inclusion criteria, and 8 had a complication (10%). A significant difference in complication rate was seen among groups ( P = .01) but not rate of readmission or reoperation. Of 16 patients, 5 (31%) who were admitted for 2 or more nights following surgery had a complication, as opposed to 3 of 65 (5%) who were outpatient or admitted overnight ( P = .01). There were no differences in frequency of postoperative phone calls, narcotic refills, or visual analog scale pain scores at the first postoperative visit. There were no adverse medical events. CONCLUSION: With proper instruction, TAA was performed safely in the outpatient setting. As health care policy continues to evolve in the United States, safe and efficient practices will remain a priority. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Impact of tobacco smoke on upper airway dendritic cell accumulation and regulation by sinonasal epithelial cells.

BACKGROUND: In these studies we examined the impact of environmental tobacco smoke (ETS) and active smoking on sinonasal dendritic cell (DC) subsets in controls or patients with chronic rhinosinusitis with nasal polyps (CRSwNP). In subsequent in-vitro investigations, we examined the influence of cigarette smoke extract (CSE) on human sinonasal epithelial cells' (HSNECs) ability to regulate DC functions. METHODS: Sinonasal tissue, blood, and hair were collected from patients undergoing sinus surgery. Smoking status and ETS exposure were determined by hair nicotine. DC subsets were examined by flow cytometric analysis. Monocyte-derived dendritic cells (moDCs) were treated with conditioned medium from non-smoked-exposed HSNECs (NS-HSNECs) or cigarette-smoke-extract-exposed HSNECs (CSE-HSNECs) to assess the impact of CSE exposure on HSNEC regulation of moDC functions. RESULTS: Control subjects who were active smokers displayed increased sinonasal moDC and myeloid dendritic 1 (mDC1) cells and reduced mDC2 cells, whereas, in CRSwNP patients, only moDC and mDC2 cells were altered. ETS was found to increase only moDCs in the CRSwNP patients. In vitro, CSE stimulated HSNEC secretion of the moDC regulatory products chemokine (C-C motif) ligand 20, prostaglandin E2 , and granulocyte-macrophage colony-stimulating factor. CSE exposure also promoted HSNECs to stimulate monocyte and moDC migration. moDCs treated with CSE-HSNEC media stimulated an increase in antigen uptake and expression of CD80 and CD86. Last, CSE-HSNEC-treated moDCs secreted increased levels of interleukin-10, interferon-γ, and thymic stromal lymphopoietin. CONCLUSION: Active smoking, and to a lesser degree ETS, alters the sinonasal composition of DCs. A potential mechanism to account for this is that cigarette smoke stimulates HSNECs to induce moDC migration, maturation, and activation.

Neer Award 2016: Outpatient total shoulder arthroplasty in an ambulatory surgery center is a safe alternative to inpatient total shoulder arthroplasty in a hospital: a matched cohort study.

BACKGROUND: Recent emphasis on safe and efficient delivery of high-quality health care has increased interest in outpatient total joint arthroplasty. The purpose of this study was to evaluate the safety of outpatient total shoulder arthroplasty (TSA) by comparing episode-of-care complications in matched cohorts of patients with anatomic TSA as an outpatient or inpatient procedure. METHODS: Thirty patients with outpatient TSA at a freestanding ambulatory surgery center (ASC) were compared with an age- and comorbidities-matched cohort of 30 patients with traditional inpatient TSA to evaluate 90-day episode-of-care complications, including hospital admissions or readmissions and reoperations. Two-tailed t-tests were used to evaluate differences, and differences of P < .05 were considered statistically significant. RESULTS: No significant differences were found between the ASC and hospital cohorts regarding average age, preoperative American Society of Anesthesiologists score, operative indications, or body mass index. No patient required reoperation. There were no hospital admissions from the ASC cohort and no readmissions from the hospital cohort. Minor complications in the ASC cohort were arthrofibrosis in 2 patients and mild asymptomatic anterior subluxation in 1 patient; the only major complication was in an outpatient who fell 11 weeks after surgery and disrupted his subscapularis repair. Three minor complications in the hospital cohort were mild asymptomatic anterior subluxation, blood transfusion, and superficial venous thrombosis. The complication rates (13% vs. 10%) were not significantly different. CONCLUSIONS: Outpatient TSA is a safe alternative to hospital admission in appropriately selected patients. Further investigation is warranted to evaluate the longer term outcomes and cost-effectiveness of outpatient TSA.