Facial Soft Tissue Lesions in Children.

Facial soft tissue lesions in children are often classified based on their structure or cellular origin and can be benign or malignant. This review focuses on common facial soft tissue lesions in children, their clinical morphology, natural history, and medical and surgical management, with an emphasis on those considerations unique to soft tissue lesions present at this anatomic site.

Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage.

Recent studies of severe acute inflammatory lung disease including COVID-19 identify macrophages to drive pulmonary hyperinflammation and long-term damage such as fibrosis. Here, we report on the development of a first-in-class, carbohydrate-coupled inhibitor of microRNA-21 (RCS-21), as a therapeutic means against pulmonary hyperinflammation and fibrosis. MicroRNA-21 is among the strongest upregulated microRNAs in human COVID-19 and in mice with acute inflammatory lung damage, and it is the strongest expressed microRNA in pulmonary macrophages. Chemical linkage of a microRNA-21 inhibitor to trimannose achieves rapid and specific delivery to macrophages upon inhalation in mice. RCS-21 reverses pathological activation of macrophages and prevents pulmonary dysfunction and fibrosis after acute lung damage in mice. In human lung tissue infected with SARS-CoV-2 ex vivo, RCS-21 effectively prevents the exaggerated inflammatory response. Our data imply trimannose-coupling for effective and selective delivery of inhaled oligonucleotides to pulmonary macrophages and report on a first mannose-coupled candidate therapeutic for COVID-19.

Second Harmonic Generation Microscopy as a Novel Intraoperative Assessment of Rat Median Nerve Injury.

PURPOSE: Nerves that are functionally injured but appear macroscopically intact pose the biggest clinical dilemma. Second Harmonic Generation (SHG) Microscopy may provide a real-time assessment of nerve damage, with the ultimate goal of allowing surgeons to accurately quantify the degree of nerve damage present. The aim of this study was to demonstrate the utility of SHG microscopy to detect nerve damage in vivo in an animal model. METHODS: Ten Sprague-Dawley rats were anesthetized and prepared for surgery. After surgical exposure and using a custom-made stretch applicator, the right median nerves were stretched by 20%, corresponding to a high strain injury, and held for 5 minutes. The left median nerve served as a sham control (SC), only being placed in the applicator for 5 minutes with no stretch. A nerve stimulator was used to assess the amount of stimulation required to induce a flicker and contraction of the paw. Nerves were then imaged using a multiphoton laser scanning microscope. RESULTS: Immediately after injury (day 0), SHG images of SC median nerves exhibited parallel collagen fibers with linear, organized alignment. In comparison with SC nerves, high strain nerves demonstrated artifacts indicative of nerve damage consisting of wavy, undulating fibers with crossing fibers and tears, as well as a decrease in the linear organization, which correlated with an increase in the mean stimulation required to induce a flicker and contraction of the paw. CONCLUSIONS: Second Harmonic Generation microscopy may provide the ability to detect an acute neural stretch injury in the rat median nerve. Epineurial collagen disorganization correlated with the stimulation required for nerve function. CLINICAL RELEVANCE: In the future, SHG may provide the ability to visualize nerve damage intraoperatively, allowing for better clinical decision-making. However, this is currently a research tool and requires further validation before translating to the clinical setting.

Outcomes of Arthroscopic Elbow Contracture Release: Improvement for Severe Prosupination and Flexion Contracture.

PURPOSE: The purpose of this study was to investigate outcomes following arthroscopic elbow contracture release to describe the use of arthroscopy for improvement in extension/flexion and pronation/supination arcs of motion at a single institution for degenerative and posttraumatic etiologies. METHODS: Consecutive arthroscopic elbow arthrolysis performed between 2003 and 2015 were retrospectively reviewed. Basic patient demographics, indications for surgery, preoperative and postoperative elbow range of motion, postoperative patient outcome score, and all complications were recorded and analyzed. RESULTS: Fifty-two patients were included with an average follow-up of 5.1 years (range 1.4 to 9.4). Severe contractures made up 50% of cases, followed by 23% moderate, and 27% mild. Average extension/flexion for the post-traumatic group (n = 30) increased by 63° ± 31 and by 29° ± 24 for the degenerative group (n = 22). Average gain in pronosupination was 38° ± 62 in the post-traumatic group and 13°±23 in the degenerative group. Postoperative DASH scores were 17.5 ± 18.4 for post-traumatic cases and 12.8 ± 19.3 for degenerative cases. CONCLUSION: Arthroscopic elbow contracture release is an effective intervention for degenerative and post-traumatic elbow contracture for both flexion/extension and pronosupination contracture. Furthermore, a two-stage release should be considered when both flexion and pronosupinaton contractures are present. LEVEL OF EVIDENCE: IV, case series, treatment study.

Cra and cAMP Receptor Protein Have Opposing Roles in the Regulation of fruB in Vibrio cholerae.

The Gram-negative bacterium Vibrio cholerae adapts to changes in the environment by selectively producing the necessary machinery to take up and metabolize available carbohydrates. The import of fructose by the fructose-specific phosphoenolpyruvate (PEP) phosphotransferase system (PTS) is of particular interest because of its putative connection to cholera pathogenesis and persistence. Here, we describe the expression and regulation of fruB, which encodes an EIIA-FPr fusion protein as part of the fructose-specific PTS in V. cholerae Using a series of transcriptional reporter fusions and additional biochemical and genetic assays, we identified Cra (catabolite repressor/activator) and cAMP receptor protein (CRP) as regulators of fruB expression and determined that this regulation is dependent upon the presence or absence of PTS sugars. Cra functions as a repressor, downregulating fruB expression in the absence of fructose when components of PTSFru are not needed. CRP functions as an activator of fruB expression. We also report that Cra and CRP can affect fruB expression independently; however, CRP can modulate cra expression in the presence of fructose and glucose. Evidence from this work provides the foundation for continued investigations into PTSFru and its relationship to the V. cholerae life cycle.IMPORTANCEVibrio cholerae is the causative agent of cholera disease. While current treatments of care are accessible, we still lack an understanding of the molecular mechanisms that allow V. cholerae to survive in both aquatic reservoirs and the human small intestine, where pathogenesis occurs. Central to V. cholerae's survival is its ability to use available carbon sources. Here, we investigate the regulation of fruB, which encodes a protein central to the import and metabolism of fructose. We show that fruB expression is controlled by the transcriptional regulators Cra and CRP. This work contributes toward a clearer understanding of how carbon source availability impacts the physiology and, potentially, the persistence of the pathogen.

MicroRNA-21-Dependent Macrophage-to-Fibroblast Signaling Determines the Cardiac Response to Pressure Overload.

BACKGROUND: Cardiac macrophages (cMPs) are increasingly recognized as important regulators of myocardial homeostasis and disease, yet the role of noncoding RNA in these cells is largely unknown. Small RNA sequencing of the entire miRNomes of the major cardiac cell fractions revealed microRNA-21 (miR-21) as the single highest expressed microRNA in cMPs, both in health and disease (25% and 43% of all microRNA reads, respectively). MiR-21 has been previously reported as a key microRNA driving tissue fibrosis. Here, we aimed to determine the function of macrophage miR-21 on myocardial homeostasis and disease-associated remodeling. METHODS: Macrophage-specific ablation of miR-21 in mice driven by Cx3cr1-Cre was used to determine the function of miR-21 in this cell type. As a disease model, mice were subjected to pressure overload for 6 and 28 days. Cardiac function was assessed in vivo by echocardiography, followed by histological analyses and single-cell sequencing. Cocultures of macrophages and cardiac fibroblasts were used to study macrophage-to-fibroblast signaling. RESULTS: Mice with macrophage-specific genetic deletion of miR-21 were protected from interstitial fibrosis and cardiac dysfunction when subjected to pressure overload of the left ventricle. Single-cell sequencing of pressure-overloaded hearts from these mice revealed that miR-21 in macrophages is essential for their polarization toward a M1-like phenotype. Systematic quantification of intercellular communication mediated by ligand-receptor interactions across all cell types revealed that miR-21 primarily determined macrophage-fibroblast communication, promoting the transition from quiescent fibroblasts to myofibroblasts. Polarization of isolated macrophages in vitro toward a proinflammatory (M1-like) phenotype activated myofibroblast transdifferentiation of cardiac fibroblasts in a paracrine manner and was dependent on miR-21 in cMPs. CONCLUSIONS: Our data indicate a critical role of cMPs in pressure overload-induced cardiac fibrosis and dysfunction and reveal macrophage miR-21 as a key molecule for the profibrotic role of cMPs.

The ß-encapsulation cage of rearrangement hotspot (Rhs) effectors is required for type VI secretion.

Bacteria deploy rearrangement hotspot (Rhs) proteins as toxic effectors against both prokaryotic and eukaryotic target cells. Rhs proteins are characterized by YD-peptide repeats, which fold into a large ß-cage structure that encapsulates the C-terminal toxin domain. Here, we show that Rhs effectors are essential for type VI secretion system (T6SS) activity in Enterobacter cloacae (ECL). ECL rhs- mutants do not kill Escherichia coli target bacteria and are defective for T6SS-dependent export of hemolysin-coregulated protein (Hcp). The RhsA and RhsB effectors of ECL both contain Pro-Ala-Ala-Arg (PAAR) repeat domains, which bind the ß-spike of trimeric valine-glycine repeat protein G (VgrG) and are important for T6SS activity in other bacteria. Truncated RhsA that retains the PAAR domain is capable of forming higher-order, thermostable complexes with VgrG, yet these assemblies fail to restore secretion activity to ∆rhsA ∆rhsB mutants. Full T6SS-1 activity requires Rhs that contains N-terminal transmembrane helices, the PAAR domain, and an intact ß-cage. Although ∆rhsA ∆rhsB mutants do not kill target bacteria, time-lapse microscopy reveals that they assemble and fire T6SS contractile sheaths at ∼6% of the frequency of rhs+ cells. Therefore, Rhs proteins are not strictly required for T6SS assembly, although they greatly increase secretion efficiency. We propose that PAAR and the ß-cage provide distinct structures that promote secretion. PAAR is clearly sufficient to stabilize trimeric VgrG, but efficient assembly of T6SS-1 also depends on an intact ß-cage. Together, these domains enforce a quality control checkpoint to ensure that VgrG is loaded with toxic cargo before assembling the secretion apparatus.

The Early Effects of COVID-19 on Plastic Surgery Residency Training: The University of Washington Experience.

Plastic surgeons have the unique perspective of working with all types of patients and care teams from almost all specialties in surgery and medicine, which creates unique challenges in times of distress. As the initial epicenter of coronavirus disease 2019 cases in the United States, the University of Washington program was required to rapidly develop strategies to deal with the escalating crisis. All aspects of the program were affected, including the need to triage the urgency of plastic surgery care, safe staffing of plastic surgery teams, and the role of plastic surgery in the greater hospital community. In addition, as a residency training program, limiting the impact of resident education and maintaining a sense of community and connection among members of the program developed into important considerations. The authors hope that the narrative of their experience will provide insight into the decisions made in the University of Washington health care system but also remind others that they are not alone in dealing with the challenges of this pandemic.

AntimiR-21 Prevents Myocardial Dysfunction in a Pig Model of Ischemia/Reperfusion Injury.

BACKGROUND: miR-21 is a central regulator of cardiac fibrosis, and its inhibition in small-animal models has been shown to be an effective antifibrotic strategy in various organs, including the heart. Effective delivery of therapeutic antisense micro-ribonucleic acid (antimiR) molecules to the myocardium in larger organisms is challenging, though, and remains to be established for models of chronic heart failure. OBJECTIVES: The aims of this study were to test the applicability and therapeutic efficacy of local, catheter-based delivery of antimiR-21 in a pig model of heart failure and determine its effect on the cardiac transcriptomic signature and cellular composition. METHODS: Pigs underwent transient percutaneous occlusion of the left coronary artery and were followed up for 33 days. AntimiR-21 (10 mg) was applied by intracoronary infusion at days 5 and 19 after the injury. Cardiac function was assessed in vivo, followed by histological analyses and deep ribonucleic acid sequencing (RNA-seq) of the myocardium and genetic deconvolution analysis. RESULTS: AntimiR-21 effectively suppressed the remodeling-associated increase of miR-21. At 33 days after ischemia/reperfusion injury, LNA-21-treated hearts exhibited reduced cardiac fibrosis and hypertrophy and improved cardiac function. Deep RNA-seq revealed a significant derepression of the miR-21 targetome in antimiR-21-treated myocardium and a suppression of the inflammatory response and mitogen-activated protein kinase signaling. A genetic deconvolution approach built on deep RNA-seq and single-cell RNA-seq data identified reductions in macrophage and fibroblast numbers as the key cell types affected by antimiR-21 treatment. CONCLUSIONS: This study provides the first evidence for the feasibility and therapeutic efficacy of miR-21 inhibition in a large animal model of heart failure.

Impact of CT scanner location on door to imaging time for emergency department stroke evaluation.

BACKGROUND AND OBJECTIVES: Stroke is a potentially serious condition commonly diagnosed in the ED. Time to diagnosis can be crucial to maximizing outcome in a majority of ischemic stroke cases amenable to thrombolytic therapy. METHODS: An analysis of 148 consecutive adults transported by EMS to an urban emergency department with a diagnosis of cerebro-vascular accident during a 12 month period was performed to determine the impact of CT scanner location on door-to-head CT [DTCT] scan time. The CT scanner was relocated from an upper floor of the hospital to within the ER department midway through the study period. RESULTS: The rate of DTCT scan time ≤20 min increased significantly from 47% [pre-relocation] to 74% [post-relocation]; and the rate of DTCT ultra-rapid scan time ≤10 min more than doubled. CONCLUSIONS: Hospitals providing ED care for stroke patients can expedite management by ensuring CT scanner location is in closest possible proximity to the ED.

Comparative strength of elbow splint designs: a new splint design as a stronger alternative to posterior splints.

BACKGROUND: Musculoskeletal injuries of the upper extremity are frequently treated with temporary external immobilization. Traditionally, long arm posterior splints have been used to limit flexion/extension of the elbow. However, long arm posterior splints have been observed to fail clinically, necessitating a stronger alternative. In this study, we assessed the biomechanical strength of the long arm posterior splint compared with a new spiral splint design. METHODS: One male and one female participant were placed 10 times in long arm posterior splints and 10 times in spiral splints. Both splint types were subjected to a downward mechanical load of 39.2 N (4 kg) and assessed for a change in both flexion/extension and pronation/supination. RESULTS: There was no significant difference in starting position or starting flexion/extension between the 2 splint designs. Posterior splints allowed significantly greater initial pronation/supination compared with spiral splints. Both splint groups had significant increases in flexion/extension and pronation/supination compared with their starting ranges of motion. There was no significant difference in the change in pronation/supination between the 2 splint groups. Finally, posterior splints allowed a significantly greater change in flexion/extension compared with spiral splints. CONCLUSION: Spiral splints offered less initial pronation/supination than long arm posterior splints. Furthermore, spiral splints are able to resist flexion/extension of the elbow after application of a downward mechanical load better than posterior splints, thus suggesting spiral splints are mechanically superior to long arm posterior splints.

Intramedullary Screw Fixation of Metacarpal Fractures Results in Excellent Functional Outcomes: A Literature Review.

BACKGROUND: Intramedullary fixation of a comminuted subcapital metacarpal fracture using a headless compression screw was first described in 2010. The purpose of this study was to identify and evaluate all studies reporting clinical outcomes of intramedullary screw fixation of metacarpal fractures. METHODS: A comprehensive search of the literature was performed under Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to identify all relevant studies. Outcome measures included mean follow-up, evidence of radiographic union, functional outcomes, and quality-of-life measures. RESULTS: Nine articles for a total of 169 metacarpal fractures were identified. Average patient age was 32 years; 86.5 percent of the patients were men; and the majority of fractures occurred in the small finger (74 percent). Most fractures occurred in the neck (n = 66), followed by shaft (n = 31) and head (n = 10). The average follow-up was 11 months, with an average metacarpophalangeal joint flexion of 86 degrees (n = 83) and digit total active motion of 251 degrees (n = 72). Radiographic union was achieved in 100% of reported cases (n = 132) at or before the latest follow-up. Grip strength in four studies showed an average of 96 percent compared to the contralateral hand. No serious complications were reported. Nine minor complications were reported, including four cases of hardware removal in asymptomatic patients. CONCLUSION: The review of the literature suggests intramedullary fixation of metacarpal neck and shaft fractures using headless compression screws has thus far proven to be a safe and successful surgical treatment option resulting in excellent clinical outcomes.

Varus posteromedial rotatory instability: a biomechanical analysis of posterior bundle of the medial ulnar collateral ligament reconstruction.

BACKGROUND: Recently, there has been growing interest in the involvement of the posterior bundle of the medial ulnar collateral ligament (pMUCL) in varus posteromedial rotatory instability (PMRI). Varus PMRI has been observed clinically, but the degree of involvement of the pMUCL remains unclear. This study assessed the degree to which the pMUCL is involved in stabilizing the elbow and the feasibility of a pMUCL reconstruction to restore stability. METHODS: Movements simulating PMRI were performed in 8 cadaveric elbows. Joint gapping values were obtained by 3-dimensional motion capture for the proximal and distal aspects of the ulnohumeral joint. Specimens were assessed at "intact," "cut coronoid + pMUCL," "reconstruction," and "cut anterior aspect MUCL + reconstruction" conditions with mechanical testing at 30°, 60°, and 90° of elbow flexion. RESULTS: Proximal joint gapping significantly increased from intact to cut coronoid + pMUCL at 60° and 90°, and distal joint gapping significantly increased at 90°. In the reconstruction condition, joint gapping across the proximal joint at 60° and 90° significantly recovered, as did distal joint gapping at 90°. In the cut anterior aspect MUCL + reconstruction condition, no significant increase occurred in proximal or distal joint gapping. CONCLUSIONS: Transection of the pMUCL with a coronoid fracture leads to increased joint gapping, suggesting the presence of PMRI. PMRI can still occur with an intact lateral ligamentous complex. A pMUCL tendon graft reconstruction confers some elbow stability in this injury mechanism.

The effect of screw trajectory for the reduction and association of the scaphoid and lunate (RASL) procedure: a biomechanical analysis.

The purpose of this study was to determine if screw placement in the reduction and association of the scaphoid and the lunate (RASL) procedure affected the ability of the scapholunate joint to withstand force. After completely disrupting of the scapholunate ligament in 29 fresh-frozen cadaveric wrists, we placed the RASL screw either distal or proximal to the lateral aspect of the dorsal ridge of the scaphoid and into the dorsal or volar aspect of the lunate. Specimens were subjected to repeated cycles of transcarpal axial force, mimicking clenched-fist loading, until failure. Screw placement distal to the lateral aspect of the dorsal scaphoid ridge was significantly associated with failure when examined manually, radiographically (1.8 vs. 0.5 mm) and using real-time motion capture (diastasis: 1.6 vs. 0.4 mm; Euler angle: 4.5 ° vs. 0.8 °). The lateral aspect of the dorsal ridge is a reliable radiographic landmark on the scaphoid and provides surgeons with a convenient starting point to achieve the most biomechanically stable RASL construct, and, therefore, enhances the potential for an optimal clinical outcome.

Activation of an anti-bacterial toxin by the biosynthetic enzyme CysK: mechanism of binding, interaction specificity and competition with cysteine synthase.

Contact-dependent growth inhibition (CDI) is a wide-spread mechanism of inter-bacterial competition. CDI+ bacteria deliver CdiA-CT toxins into neighboring bacteria and produce specific immunity proteins that protect against self-intoxication. The CdiA-CT toxin from uropathogenic Escherichia coli 536 is a latent tRNase that is only active when bound to the cysteine biosynthetic enzyme CysK. Remarkably, the CysK:CdiA-CT binding interaction mimics the 'cysteine synthase' complex of CysK:CysE. The C-terminal tails of CysE and CdiA-CT each insert into the CysK active-site cleft to anchor the respective complexes. The dissociation constant for CysK:CdiA-CT (K d ~ 11 nM) is comparable to that of the E. coli cysteine synthase complex (K d ~ 6 nM), and both complexes bind through a two-step mechanism with a slow isomerization phase after the initial encounter. However, the second-order rate constant for CysK:CdiA-CT binding is two orders of magnitude slower than that of the cysteine synthase complex, suggesting that CysE should outcompete the toxin for CysK occupancy. However, we find that CdiA-CT can effectively displace CysE from pre-formed cysteine synthase complexes, enabling toxin activation even in the presence of excess competing CysE. This adventitious binding, coupled with the very slow rate of CysK:CdiA-CT dissociation, ensures robust nuclease activity in target bacteria.

CdiA Effectors Use Modular Receptor-Binding Domains To Recognize Target Bacteria.

Contact-dependent growth inhibition (CDI) systems encode CdiA effectors, which bind to specific receptors on neighboring bacteria and deliver C-terminal toxin domains to suppress target cell growth. Two classes of CdiA effectors that bind distinct cell surface receptors have been identified, but the molecular basis of receptor specificity is not understood. Alignment of BamA-specific CdiAEC93 from Escherichia coli EC93 and OmpC-specific CdiAEC536 from E. coli 536 suggests that the receptor-binding domain resides within a central region that varies between the two effectors. In support of this hypothesis, we find that CdiAEC93 fragments containing residues Arg1358 to Phe1646 bind specifically to purified BamA. Moreover, chimeric CdiAEC93 that carries the corresponding sequence from CdiAEC536 is endowed with OmpC-binding activity, demonstrating that this region dictates receptor specificity. A survey of E. coli CdiA proteins reveals two additional effector classes, which presumably recognize distinct receptors. Using a genetic approach, we identify the outer membrane nucleoside transporter Tsx as the receptor for a third class of CdiA effectors. Thus, CDI systems exploit multiple outer membrane proteins to identify and engage target cells. These results underscore the modularity of CdiA proteins and suggest that novel effectors can be constructed through genetic recombination to interchange different receptor-binding domains and toxic payloads.IMPORTANCE CdiB/CdiA two-partner secretion proteins mediate interbacterial competition through the delivery of polymorphic toxin domains. This process, known as contact-dependent growth inhibition (CDI), requires stable interactions between the CdiA effector protein and specific receptors on the surface of target bacteria. Here, we localize the receptor-binding domain to the central region of E. coli CdiA. Receptor-binding domains vary between CdiA proteins, and E. coli strains collectively encode at least four distinct effector classes. Further, we show that receptor specificity can be altered by exchanging receptor-binding regions, demonstrating the modularity of this domain. We propose that novel CdiA effectors are naturally generated through genetic recombination to interchange different receptor-binding domains and toxin payloads.

Risk factors for and timing of adverse events after total shoulder arthroplasty.

BACKGROUND: Total shoulder arthroplasty (TSA) is a likely target for future bundled payment initiatives, necessitating accurate preoperative risk stratification. The purpose of this study was to identify risk factors for unplanned readmission and severe adverse events, to risk stratify TSA patients based on these risk factors, and to assess timing of complications after TSA. METHODS: Data were collected from patients undergoing TSA from 2009 to 2014 in the American College of Surgeons National Surgical Quality Improvement Program. Bivariate and multivariate analyses of risk factors for severe adverse events or readmission were assessed. Patients were risk stratified, and timing of severe adverse events and cause of readmission were evaluated. RESULTS: The analysis included 5801 TSA patients; 146 (2.5%) suffered severe adverse events, and 158 (2.7%) had a 30-day unplanned readmission. The most common severe adverse events were reoperation (40%), thrombolic event (deep venous thrombosis or pulmonary embolism; 14%), cardiac event (10%), and death (8.2%). Pneumonia (8.9%) and thrombolic event (7.6%) were the most common medically related causes, whereas dislocation (7.6%) and postoperative infection or wound complication (5.1%) were the most common surgical causes for readmission. Multivariate analysis identified inflammatory arthritis (P = .026), male gender (P = .019), age (P < .001), functional status (P = .024), and American Society of Anesthesiologists class 3/4 (P = .01) as independent predictors for unplanned 30-day readmission and all but inflammatory arthritis for severe adverse events (P ≤ .05 for all). Patients with ≥3 risk factors had an 11.56 (P = .002) and 3.43 (P = .013) times increased odds of unplanned readmission and severe adverse events occurring within 2 weeks after surgery, respectively, compared with patients with 0 risk factors. CONCLUSIONS: Patients at high risk of TSA complications and readmission should be identified preoperatively to improve outcomes and to lower costs. Bundled payment initiatives must account for both patient- and procedure-related risk factors.

CdiA Effectors from Uropathogenic Escherichia coli Use Heterotrimeric Osmoporins as Receptors to Recognize Target Bacteria.

Many Gram-negative bacterial pathogens express contact-dependent growth inhibition (CDI) systems that promote cell-cell interaction. CDI+ bacteria express surface CdiA effector proteins, which transfer their C-terminal toxin domains into susceptible target cells upon binding to specific receptors. CDI+ cells also produce immunity proteins that neutralize the toxin domains delivered from neighboring siblings. Here, we show that CdiAEC536 from uropathogenic Escherichia coli 536 (EC536) uses OmpC and OmpF as receptors to recognize target bacteria. E. coli mutants lacking either ompF or ompC are resistant to CDIEC536-mediated growth inhibition, and both porins are required for target-cell adhesion to inhibitors that express CdiAEC536. Experiments with single-chain OmpF fusions indicate that the CdiAEC536 receptor is heterotrimeric OmpC-OmpF. Because the OmpC and OmpF porins are under selective pressure from bacteriophages and host immune systems, their surface-exposed loops vary between E. coli isolates. OmpC polymorphism has a significant impact on CDIEC536 mediated competition, with many E. coli isolates expressing alleles that are not recognized by CdiAEC536. Analyses of recombinant OmpC chimeras suggest that extracellular loops L4 and L5 are important recognition epitopes for CdiAEC536. Loops L4 and L5 also account for much of the sequence variability between E. coli OmpC proteins, raising the possibility that CDI contributes to the selective pressure driving OmpC diversification. We find that the most efficient CdiAEC536 receptors are encoded by isolates that carry the same cdi gene cluster as E. coli 536. Thus, it appears that CdiA effectors often bind preferentially to "self" receptors, thereby promoting interactions between sibling cells. As a consequence, these effector proteins cannot recognize nor suppress the growth of many potential competitors. These findings suggest that self-recognition and kin selection are important functions of CDI.

Day of Surgery and Surgical Start Time Affect Hospital Length of Stay After Total Hip Arthroplasty.

BACKGROUND: The United States spends $12 billion each year on ∼332,000 total hip arthroplasty (THA) procedures with the postoperative period accounting for ∼40% of costs. The purpose of this study was to evaluate the effect of surgical scheduling (day of week and start time) on clinical outcomes, hospital length of stay (LOS), and rate of nonhome discharge in THA patients. METHODS: Analysis of perioperative variables was performed for patients who underwent THA at an urban tertiary care teaching hospital from 2009 to 2014. RESULTS: A total of 580 THA patients were included for analysis. LOS was higher for the Thursday/Friday cohort compared to Monday/Tuesday (3.7 vs 3.4 days; P = .03). Patients who had a surgical start time after 2 PM had longer LOS compared to patients operated on before 2 PM (3.9 vs 3.5 days; P = .03). After controlling for patient comorbidities and THA surgical approach (direct anterior vs posterior), Thursday/Friday THAs were associated with a 3.27 times risk of extended LOS (>75th percentile LOS) compared to Monday/Tuesday THAs (P < .001). Additionally, case start before 2 PM was protective and associated with a 0.46 times odds of extended LOS (P = .01). LOS reduction opportunity for changing surgical start time to before 2 PM was 0.9 days for high-risk patients (American Society of Anesthesiology class 3/4 and/or liver disease) and 0.2 days for low-risk patients (American Society of Anesthesiology class 1/2). CONCLUSION: Patients who underwent THA Thursday/Friday or had start times after 2 PM had significantly extended hospital LOS. Preoperative risk modification along with adjustments to surgical scheduling and/or perioperative staffing may reduce LOS and thus hospital expenditures for THA procedures.