Indications for Augmenting Arthroscopic Bankart Procedure with Remplissage in Patients with Non-engaging Hill-Sachs Lesions Must Be Individualized Based on Surgeon and Patient.

Arthroscopic remplissage has been suggested as a means to decrease recurrent instability in arthroscopic Bankart repair surgery involving patients with significant Hill-Sachs lesions. Remplissage fills the H-S lesion to prevent glenohumeral "engagement" and recurrent instability. Remplissage is not generally indicated in patients with smaller, non-engaging Hill-Sachs lesions. However, a recent review suggests that by expanding the indications to non-engaging H-S lesions, recurrence of shoulder instability may be lower in patients having arthroscopic Bankart repair. Further, the review suggests that patients having Bankart plus remplissage did not lose shoulder external rotation range-of-motion. A concern, in addition to follow-up that likely results in underestimation of recurrence, is that anatomically, remplissage should decrease external rotation, and manual measurement of ER could reflect compensatory scapulothoracic motion. This is a particular problem for throwing athletes.

Editorial Commentary: Return to Play in Overhead Athletes After Biceps Tenodesis for SLAP Lesions Is Inconsistent.

The optimal surgical management for the superior labrum anterior to posterior (SLAP) lesion in the overhead athlete remains elusive. Return to play (RTP) or return to sport (RTS) with both SLAP repair and biceps tenodesis in this subgroup has been inconsistent, complicated by incomplete description of what RTP actually involves. While the recent literature regarding biceps tenodesis for SLAP lesions is encouraging, longer-term follow-up and a clear definition of criteria that define what "RTP" looks like will be critical prior to universally embracing biceps tenodesis as a definitive SLAP management option for overhead athletes.

Editorial Commentary: Extreme Medial Repair of Massive Rotator Cuff Tears With Atrophy Warrants Caution: Robbing Peter to Pay Paul.

Medialization of the rotator cuff insertion as a technique to manage massive rotator cuff tears has been described for decades. However, "extreme medialization" as a means to manage massive rotator cuff tears with significant atrophy warrants caution. Nonanatomic reconstruction almost always carries a price. Biomechanical studies show extreme medialization results in significant and obligate restriction of motion, and it is difficult to imagine how extreme medialization would allow normal clinical motion without substantial scapulothoracic compensation. Similarly, obligatory loss of strength could be expected. Based on the current evidence, I will not indicate this technique for my own patients at the present time.

Editorial Commentary: To Properly Apply Delphi Consensus Conclusions, Strengths and Weaknesses of the Process Require Consideration: Unified Expert Opinion or Toxic Fumes Resulting in a Strange Trance?

The Delphi Consensus Process is a tool to allow diverse expert opinion to be consolidated to better understand complex problems. The process has recently been applied to orthopaedic treatment options. While a piece of the puzzle, the strengths and weaknesses of this process must be understood to allow the orthopaedist to apply the conclusions of the Delphi Consensus process effectively. It is important to recognize that expert opinion has been upended time and time again by carefully collected clinical-outcome data. It is unclear whether the visions of the Oracle are due to wisdom or toxic fumes resulting in a strange trance.

Editorial Commentary: The Top Cited Rotator Cuff Repair Articles: It's All About Popular.

The Thomson Institute for Scientific Information Web of Science database was used to rank the top 50 articles regarding rotator cuff repair by number of citations received. Although the number of citations is a useful benchmark, it must be taken as only one of many indices of the value of an article to the study of orthopaedics. The most cited articles are out of date, reflecting that a longer time in publication allows more time for citation, and most have low levels of evidence (Level IV, retrospective case series absent a control group).

Editorial Commentary: Mechanics Versus Biology: Both Are Relevant Principles in Understanding Superior Capsular Reconstruction.

The topic of superior capsular reconstruction remains controversial. Whereas identifying the best time-zero graft configuration for this procedure remains important, the success or failure of the procedure will be dependent on the biology, not just the bench performance. Any conforming object placed in the subacromial space at time zero could center the humeral head and decrease superior translation compared with a massive rotator cuff tear but may not restore translation to normal. It does appear that a thicker graft is better in this regard, but how much thicker is better is unclear. Most of all, whether the mechanical benefits of a thicker graft will be offset by a thicker and potentially less biologically compatible construct is also unclear. In most orthopaedic settings, autografts remain consistently superior to allografts. The contrast in results may be better explained by biology, and the excellent superior capsular reconstruction results reported with autograft have not been replicated universally with dermal allograft.

Electroosmotic Perfusion-Microdialysis Probe Created by Direct Laser Writing for Quantitative Assessment of Leucine Enkephalin Hydrolysis by Insulin-Regulated Aminopeptidase in Vivo.

There are many processes that actively alter the concentrations of solutes in the extracellular space. Enzymatic reactions, either by soluble enzymes or membrane-bound ectoenzymes, and uptake or clearance are two such processes. Investigations of ectoenzymatic reactions in vivo is challenging, particularly in the brain. Studies using microdialysis have revealed some qualitative information about what enzymes may be present, but microdialysis is a sampling technique so it is not designed to control conditions such as a substrate concentration outside the probe. Micropush-pull perfusion has been used to determine which nitric oxide synthase enzymes are active in discrete regions of the rat retina. Ectopeptidases are a particularly important class of ectoenzymes. As far as it is known, the extracellular activity of active peptides in the brain is controlled by ectopeptidases. To understand ectopeptidase activity, we developed a physical probe and an accompanying method. The probe has a two-channel source that supplies substrate or substrate plus inhibitor using electroosmotic perfusion (EOP). It also has a microdialysis probe to collect products and unreacted substrate. The method provides quantitative estimates of substrate-to-product conversion and the influence of inhibitors on this process. The quantitative estimates are made possible by including a d-amino acid-containing peptide analog of the substrate in the substrate-containing solution infused. Quantitative analysis of substrate, substrate analog, and products is carried out by quantitative, online capillary liquid chromatography-tandem mass spectrometry. The electroosmotic perfusion-microdialysis probe and associated method were used to determine the effect of the selective inhibitor HFI-419 on insulin-regulated aminopeptidase (EC 3.4.11.3) in the rat neocortex.

Neighborhood Disadvantage and Hospital Quality Ratings in the Medicare Hospital Compare Program.

BACKGROUND: The Centers for Medicare and Medicaid Services provide nationwide hospital ratings that may influence reimbursement. These ratings do not account for the social risk of communities and may inadvertently penalize hospitals that service disadvantaged neighborhoods. OBJECTIVE: This study examines the relationship between neighborhood social risk factors (SRFs) and hospital ratings in Medicare's Hospital Compare Program. RESEARCH DESIGN: 2017 Medicare Hospital Compare ratings were linked with block group data from the 2015 American Community Survey to assess hospital ratings as a function of neighborhood SRFs. SUBJECTS: A total of 3608 Medicare-certified hospitals in 50 US states. MEASURES: Hospital summary scores and 7 quality group scores (100 percentile scale), including effectiveness of care, efficiency of care, hospital readmission, mortality, patient experience, safety of care, and timeliness of care. RESULTS: Lower hospital summary scores were associated with caring for neighborhoods with higher social risk, including a reduction in hospital score for every 10% of residents who reported dual-eligibility for Medicare/Medicaid [-3.3%; 95% confidence interval (CI), -4.7 to -2.0], no high-school diploma (-0.8%; 95% CI, -1.5 to -0.1), unemployment (-1.2%; 95% CI, -1.9 to -0.4), black race (-1.2%; 95% CI, -1.7 to -0.8), and high travel times to work (-2.5%; 95% CI, -3.3 to -1.6). Associations between neighborhood SRFs and hospital ratings were largest in the timeliness of care, patient experience, and hospital readmission groups; and smallest in the safety, efficiency, and effectiveness of care groups. CONCLUSIONS: Hospitals serving communities with higher social risk may have lower ratings because of neighborhood factors. Failing to account for neighborhood social risk in hospital rating systems may reinforce hidden disincentives to care for medically underserved areas in the United States.

Editorial Commentary: Stem Cells in Rotator Cuff Surgery: In Search of the Holy Grail.

The use of stem cells in orthopaedics remains a controversial topic, stem cells remain experimental, and significant concerns exist. Studies evaluating diagnoses that may spontaneously resolve could be of low value absent a control group. Only same-day harvest of minimally manipulated stem cells is approved for use in the United States, and these minimally manipulated products may contain insufficient cells to affect outcomes. Extensively cultured cells do not qualify for use in the United States outside of an approved Investigational New Drug Application. Moreover, in other arenas, significant, serious adverse events have been reported after the use of manipulated stem cells. Both the US Food and Drug Administration and American Academy of Orthopaedic Surgeons have recognized the potential for abuse regarding this evolving technology. Published results using stems cells to treat rotator cuff disease are inconsistent, and the optimum source and preparation of the stem cells remains unknown.

Editorial Commentary: "Reversomania" Versus "SCRomania?" Another Piece of the Puzzle in the Superior Capsular Reconstruction Controversy.

The topic of superior capsular reconstruction for the massive rotator cuff tear remains a challenging subject. Multiple issues remain regarding the optimum execution of this operation, including graft type, thickness, and fixation technique. While a valuable addition to understanding the successful performance of this procedure, significant questions remain.

Multiplicative On-Column Solute Focusing Using Spatially Dependent Temperature Programming for Capillary HPLC.

The benefits of capillary liquid chromatography columns are truly realized when small, limited sample volumes require signal enhancement, but the available sample volume does not permit on-column focusing during injection onto a larger column. This dilemma is common when samples are naturally small or precious (such as in biological, forensic, art, and archeological investigations) and analyte concentrations are low. Signal enhancement by solvent-based focusing is effective with capillary columns, but it is limited to a single band-compression step and can only be achieved at the inlet. Here we evaluate multiplicative temperature-assisted solute focusing using a linear array of ten independently controlled 1.0 × 1.0 cm thermoelectric cooling elements (TECs) to generate dynamic temperature changes along the length of the column. The evaluation has two prongs: simulation and experimental. Simulation is required to understand the effect of a particular temperature change at a particular place and time on the column to determine optimal timing of temperature changes. Because the accuracy of the simulations is good, as long as the effect of temperature on retention factor is known, experimental conditions required to achieve a particular focusing objective can be estimated. We evaluated the capability of the technique to selectively focus only one of two solutes. This was achieved using three adjacent zones with temperature controlled by (upstream first) four, two, and one TECs. The three focusing steps occurring on column gave a 20-fold increase in peak height without solvent-based focusing for a solute with modest retention enthalpy.

ER remodeling by the large GTPase atlastin promotes vacuolar growth of Legionella pneumophila.

The pathogenic bacterium Legionella pneumophila replicates in host cells within a distinct ER-associated compartment termed the Legionella-containing vacuole (LCV). How the dynamic ER network contributes to pathogen proliferation within the nascent LCV remains elusive. A proteomic analysis of purified LCVs identified the ER tubule-resident large GTPase atlastin3 (Atl3, yeast Sey1p) and the reticulon protein Rtn4 as conserved LCV host components. Here, we report that Sey1/Atl3 and Rtn4 localize to early LCVs and are critical for pathogen vacuole formation. Sey1 overproduction promotes intracellular growth of L. pneumophila, whereas a catalytically inactive, dominant-negative GTPase mutant protein, or Atl3 depletion, restricts pathogen replication and impairs LCV maturation. Sey1 is not required for initial recruitment of ER to PtdIns(4)P-positive LCVs but for subsequent pathogen vacuole expansion. GTP (but not GDP) catalyzes the Sey1-dependent aggregation of purified, ER-positive LCVs in vitro Thus, Sey1/Atl3-dependent ER remodeling contributes to LCV maturation and intracellular replication of L. pneumophila.

Editorial Commentary: More Is Better? The 6-O'clock Anchor in Instability Surgery.

Placing an anchor at the 6-o'clock position on the glenoid when performing an arthroscopic Bankart repair has been suggested by multiple authors as a potential key step in improving the outcomes of arthroscopic repair. Placement of a 6-o'clock anchor increases the peak resistance force to displacement over a traditional 3-anchor repair. Determining what technique issues are relevant remains problematic, and the ultimate preferred technique remains elusive.

Regional Epidemiology of Methicillin-Resistant Staphylococcus aureus Among Adult Intensive Care Unit Patients Following State-Mandated Active Surveillance.

Background: In 2007, Illinois became the first state in the United States to mandate active surveillance of methicillin-resistant Staphylococcus aureus (MRSA). The Illinois law applies to intensive care unit (ICU) patients; contact precautions are required for patients found to be MRSA colonized. However, the effectiveness of a legislated "search and isolate" approach to reduce MRSA burden among critically ill patients is uncertain. We evaluated whether the prevalence of MRSA colonization declined in the 5 years after the start of mandatory active surveillance. Methods: All hospitals with an ICU having ≥10 beds in Chicago, Illinois, were eligible to participate in single-day serial point prevalence surveys. We assessed MRSA colonization among adult ICU patients present at time of survey using nasal and inguinal swab cultures. The primary outcome was region-wide MRSA colonization prevalence over time. Results: All 25 eligible hospitals (51 ICUs) participated in serial point prevalence surveys over 8 survey periods (2008-2013). A total of 3909 adult ICU patients participated in the point prevalence surveys, with 432 (11.1%) found to be colonized with MRSA (95% confidence interval [CI], 10.1%-12.0%). The MRSA colonization prevalence among patients was unchanged during the study period; year-over-year relative risk for MRSA colonization was 0.97 (95% CI, .89-1.05; P = .48). Conclusions: MRSA colonization prevalence among critically ill adult patients did not decline during the time period following legislatively mandated MRSA active surveillance. Our findings highlight the limits of legislated MRSA active surveillance as a strategy to reduce MRSA colonization burden among ICU patients.

TrkB-mediated activation of the phosphatidylinositol-3-kinase/Akt cascade reduces the damage inflicted by oxygen-glucose deprivation in area CA3 of the rat hippocampus.

The selective vulnerability of hippocampal area CA1 to ischemia-induced injury is a well-known phenomenon. However, the cellular mechanisms that confer resistance to area CA3 against ischemic damage remain elusive. Here, we show that oxygen-glucose deprivation-reperfusion (OGD-RP), an in vitro model that mimic the pathological conditions of the ischemic stroke, increases the phosphorylation level of tropomyosin receptor kinase B (TrkB) in area CA3. Slices preincubated with brain-derived neurotrophic factor (BDNF) or 7,8-dihydroxyflavone (7,8-DHF) exhibited reduced depression of the electrical activity triggered by OGD-RP. Consistently, blockade of TrkB suppressed the resistance of area CA3 to OGD-RP. The protective effect of TrkB activation was limited to area CA3, as OGD-RP caused permanent suppression of CA1 responses. At the cellular level, TrkB activation leads to phosphorylation of the accessory proteins SHC and Gab as well as the serine/threonine kinase Akt, members of the phosphoinositide 3-kinase/Akt (PI-3-K/Akt) pathway, a cascade involved in cell survival. Hence, acute slices pretreated with the Akt antagonist MK2206 in combination with BDNF lost the capability to resist the damage inflicted with OGD-RP. Consistently, with these results, CA3 pyramidal cells exhibited reduced propidium iodide uptake and caspase-3 activity in slices pretreated with BDNF and exposed to OGD-RP. We propose that PI-3-K/Akt downstream activation mediated by TrkB represents an endogenous mechanism responsible for the resistance of area CA3 to ischemic damage.

On-Column Dimethylation with Capillary Liquid Chromatography-Tandem Mass Spectrometry for Online Determination of Neuropeptides in Rat Brain Microdialysate.

We have developed a method for online collection and quantitation of neuropeptides in rat brain microdialysates using on-column dimethylation with capillary liquid chromatography-tandem mass spectrometry (cLC-MS2). This method addresses a number of the challenges of quantifying neuropeptides with cLC-MS. It is also a completely automated and robust method for the preparation of stable isotope labeled-peptide internal standards to correct for matrix effects and thus ensure accurate quantitation. Originally developed for tissue-derived proteomics samples ( Raijmakers et al. Mol. Cell. Proteomics 2008 , 7 , 1755 - 1762 ), the efficacy of on-column dimethylation for native peptides in microdialysate has not been demonstrated until now. We have modified the process to make it more amenable to the time scale of microdialysis sampling and to reduce the accumulation of nonvolatile contaminants on the column and, thus, loss of sensitivity. By decreasing labeling time, we have a temporal resolution of 1 h from sample loading to elution and our peptide detection limits are in the low pM range for 5 µL injections of microdialysate. We have demonstrated the effectiveness of this method by quantifying basal and potassium stimulated concentrations of the neuropeptides leu-enkephalin and met-enkephalin in the rat hippocampus. To our knowledge, this is the first report of quantitation of these peptides in the hippocampus using MS.

Formation of the Legionella-containing vacuole: phosphoinositide conversion, GTPase modulation and ER dynamics.

The environmental bacterium Legionella pneumophila replicates in free-living amoeba as well as in alveolar macrophages upon inhalation of bacteria-laden aerosols. Resistance of the opportunistic pathogen to macrophages is a prerequisite to cause a severe pneumonia called Legionnaires' disease. L. pneumophila grows intracellularly in a unique, ER-associated compartment, the Legionella-containing vacuole (LCV). The bacterial Icm/Dot type IV secretion system represents an essential virulence factor, which translocates approximately 300 "effector proteins" into protozoan or mammalian host cells. Some of these effectors contribute to the formation of the LCV by targeting conserved host factors implicated in membrane dynamics, such as phosphoinositide lipids and small GTPases. Here we review recent findings on the role of phosphoinositides, small and large GTPases as well as ER dynamics for pathogen vacuole formation and intracellular replication of L. pneumophila.

Quantitative Imaging Flow Cytometry of Legionella-Infected Dictyostelium Amoebae Reveals the Impact of Retrograde Trafficking on Pathogen Vacuole Composition.

The ubiquitous environmental bacterium Legionella pneumophila survives and replicates within amoebae and human macrophages by forming a Legionella-containing vacuole (LCV). In an intricate process governed by the bacterial Icm/Dot type IV secretion system and a plethora of effector proteins, the nascent LCV interferes with a number of intracellular trafficking pathways, including retrograde transport from endosomes to the Golgi apparatus. Conserved retrograde trafficking components, such as the retromer coat complex or the phosphoinositide (PI) 5-phosphatase D. discoideum 5-phosphatase 4 (Dd5P4)/oculocerebrorenal syndrome of Lowe (OCRL), restrict intracellular replication of L. pneumophila by an unknown mechanism. Here, we established an imaging flow cytometry (IFC) approach to assess in a rapid, unbiased, and large-scale quantitative manner the role of retrograde-linked PI metabolism and actin dynamics in the LCV composition. Exploiting Dictyostelium discoideum genetics, we found that Dd5P4 modulates the acquisition of fluorescently labeled LCV markers, such as calnexin, the small GTPase Rab1 (but not Rab7 and Rab8), and retrograde trafficking components (Vps5, Vps26, Vps35). The actin-nucleating protein and retromer interactor WASH (Wiskott-Aldrich syndrome protein [WASP] and suppressor of cAMP receptor [SCAR] homologue) promotes the accumulation of Rab1 and Rab8 on LCVs. Collectively, our findings validate IFC for the quantitative and unbiased analysis of the pathogen vacuole composition and reveal the impact of retrograde-linked PI metabolism and actin dynamics on the LCV composition. The IFC approach employed here can be adapted for a molecular analysis of the pathogen vacuole composition of other amoeba-resistant pathogens.IMPORTANCELegionella pneumophila is an amoeba-resistant environmental bacterium which can cause a life-threatening pneumonia termed Legionnaires' disease. In order to replicate intracellularly, the opportunistic pathogen forms a protective compartment, the Legionella-containing vacuole (LCV). An in-depth analysis of the LCV composition and the complex process of pathogen vacuole formation is crucial for understanding the virulence of L. pneumophila Here, we established an imaging flow cytometry (IFC) approach to assess in a rapid, unbiased, and quantitative manner the accumulation of fluorescently labeled markers and probes on LCVs. Using IFC and L. pneumophila-infected Dictyostelium discoideum or defined mutant amoebae, a role for phosphoinositide (PI) metabolism, retrograde trafficking, and the actin cytoskeleton in the LCV composition was revealed. In principle, the powerful IFC approach can be used to analyze the molecular composition of any cellular compartment harboring bacterial pathogens.

Synthesis, Structure, and Acidity Constants of Ligated α-Boryl Acetic Acids.

Basic hydrolyses of various ligated α-boryl acetic acid esters provided the first ligated derivatives of the unknown compound boroacetic acid (BH2 CH2 CO2 H). Four monoacids (L-BH2 CH2 CO2 H) and one diacid (L-BH(CH2 CO2 H)2 ) were prepared with N-heterocyclic carbene, amine, and pyridine ligands (L). The stable acids were characterized by X-ray crystallography and acidity constant (pKa ) measurements. They rank among the least acidic of all known carboxylic acids. In turn, their conjugate bases are among the strongest of all carboxylates.

Editorial Commentary: "Just When I Thought I'd Seen Everything That Could Go Wrong?" (Often Overheard in the Surgeon's Lounge): Osteonecrosis of the Humeral Head After Arthroscopic Rotator Cuff Surgery.

Osteonecrosis occurs postoperatively after rotator cuff repair, but is there a cause-and-effect relation?