Dogs: A Man's Best Friend or a Deadly Beast-A Discussion on Capnocytophaga canimorsus.

Capnocytophaga canimorsus is a catalase-positive and oxidase-positive gram-negative bacillus commonly found in dog saliva that is a rare cause of infection in immunocompromised individuals. We report the case of a 70-year-old woman with Waldenström macroglobulinemia treated with ibrutinib and a history of bilateral shoulder arthroplasty and bilateral knee arthroplasty who reported a 1-year history of multi-joint pain and swelling. The patient resides with two pet dogs that often scratch and bite, penetrating the skin, and on culture was found to have Capnocytophaga canimorsus.

The Development of Multiple Periprosthetic Joint Infections in Conjunction With Ibrutinib Therapy.

Periprosthetic joint infections (PJI) can be subcategorized into acute postoperative infections, occurring within three months of implantation, and delayed onset infections, occurring after three months of implantation. PJIs can be caused by numerous infectious etiologies. Here, we describe a unique case of a patient with a history of bilateral shoulder and knee replacements over five years. The patient received a diagnosis of Waldenströms macroglobulinemia five years before her admission but deferred ibrutinib treatment until one year before her admission. We believe that the timeline coincides with the development of multiple PJIs secondary to ibrutinib therapy. The patient presented with bilateral shoulder and knee pain and swelling, following a flu-like illness that had resolved one year before the admission. Her joint symptoms did not subside along with the remaining flu-like symptoms. Initially, her symptoms served as clues to the diagnosis; however, the diagnosis was finally made and supported by joint aspiration. The patient was treated with vancomycin 1.25 g in sodium chloride 0.9% 250 mL intravenous piggyback every 24 hours for the treatment of PJI and oral daptomycin 500 mg daily for six weeks as prophylaxis for PJI. In conclusion, physicians need to consider the development of PJIs when prescribing immunosuppressive therapy, as well as an early diagnosis to prevent further complications.

Genomic and Virological Characterization of SARS-CoV-2 Variants in a Subset of Unvaccinated and Vaccinated U.S. Military Personnel.

The emergence of SARS-CoV-2 variants complicates efforts to control the COVID-19 pandemic. Increasing genomic surveillance of SARS-CoV-2 is imperative for early detection of emerging variants, to trace the movement of variants, and to monitor effectiveness of countermeasures. Additionally, determining the amount of viable virus present in clinical samples is helpful to better understand the impact these variants have on viral shedding. In this study, we analyzed nasal swab samples collected between March 2020 and early November 2021 from a cohort of United States (U.S.) military personnel and healthcare system beneficiaries stationed worldwide as a part of the Defense Health Agency's (DHA) Global Emerging Infections Surveillance (GEIS) program. SARS-CoV-2 quantitative real time reverse-transcription PCR (qRT-PCR) positive samples were characterized by next-generation sequencing and a subset was analyzed for isolation and quantification of viable virus. Not surprisingly, we found that the Delta variant is the predominant strain circulating among U.S. military personnel beginning in July 2021 and primarily represents cases of vaccine breakthrough infections (VBIs). Among VBIs, we found a 50-fold increase in viable virus in nasal swab samples from Delta variant cases when compared to cases involving other variants. Notably, we found a 40-fold increase in viable virus in nasal swab samples from VBIs involving Delta as compared to unvaccinated personnel infected with other variants prior to the availability of approved vaccines. This study provides important insight about the genomic and virological characterization of SARS-CoV-2 isolates from a unique study population with a global presence.

NOD2/RIG-I Activating Inarigivir Adjuvant Enhances the Efficacy of BCG Vaccine Against Tuberculosis in Mice.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) kills about 1.5 million people each year and the widely used Bacille Calmette-Guérin (BCG) vaccine provides a partial protection against TB in children and adults. Because BCG vaccine evades lysosomal fusion in antigen presenting cells (APCs), leading to an inefficient production of peptides and antigen presentation required to activate CD4 T cells, we sought to boost its efficacy using novel agonists of RIG-I and NOD2 as adjuvants. We recently reported that the dinucleotide SB 9200 (Inarigivir) derived from our small molecule nucleic acid hybrid (SMNH)® platform, activated RIG-I and NOD2 receptors and exhibited a broad-spectrum antiviral activity against hepatitis B and C, Norovirus, RSV, influenza and parainfluenza. Inarigivir increased the ability of BCG-infected mouse APCs to secrete elevated levels of IL-12, TNF-α, and IFN-ß, and Caspase-1 dependent IL-1ß cytokine. Inarigivir also increased the ability of macrophages to kill MTB in a Caspase-1-, and autophagy-dependent manner. Furthermore, Inarigivir led to a Capsase-1 and NOD2- dependent increase in the ability of BCG-infected APCs to present an Ag85B-p25 epitope to CD4 T cells in vitro. Consistent with an increase in immunogenicity of adjuvant treated APCs, the Inarigivir-BCG vaccine combination induced robust protection against tuberculosis in a mouse model of MTB infection, decreasing the lung burden of MTB by 1-log10 more than that afforded by BCG vaccine alone. The Inarigivir-BCG combination was also more efficacious than a muramyl-dipeptide-BCG vaccine combination against tuberculosis in mice, generating better memory T cell responses supporting its novel adjuvant potential for the BCG vaccine.

Directly measuring the structural transition pathways of strain-engineered VO2 thin films.

Epitaxial films of vanadium dioxide (VO2) on rutile TiO2 substrates provide a means of strain-engineering the transition pathways and stabilizing of the intermediate phases between monoclinic (insulating) M1 and rutile (metal) R end phases. In this work, we investigate structural behavior of epitaxial VO2 thin films deposited on isostructural MgF2 (001) and (110) substrates via temperature-dependent Raman microscopy analysis. The choice of MgF2 substrate clearly reveals how elongation of V-V dimers accompanied by the shortening of V-O bonds triggers the intermediate M2 phase in the temperature range between 70-80 °C upon the heating-cooling cycles. Consistent with earlier claims of strain-induced electron correlation enhancement destabilizing the M2 phase our temperature-dependent Raman study supports a small temperature window for this phase. The similarity of the hysteretic behavior of structural and electronic transitions suggests that the structural transitions play key roles in the switching properties of epitaxial VO2 thin films.

Simultaneous Structural and Electronic Transitions in Epitaxial VO_{2}/TiO_{2}(001).

Recent reports have identified new metaphases of VO_{2} with strain and/or doping, suggesting the structural phase transition and the metal-to-insulator transition might be decoupled. Using epitaxially strained VO_{2}/TiO_{2} (001) thin films, which display a bulklike abrupt metal-to-insulator transition and rutile to monoclinic transition structural phase transition, we employ x-ray standing waves combined with hard x-ray photoelectron spectroscopy to simultaneously measure the structural and electronic transitions. This x-ray standing waves study elegantly demonstrates the structural and electronic transitions occur concurrently within experimental limits (±1 K).

An autophagy-inducing and TLR-2 activating BCG vaccine induces a robust protection against tuberculosis in mice.

Mycobacterium bovis BCG is widely used as a vaccine against tuberculosis due to M. tuberculosis (Mtb), which kills millions of people each year. BCG variably protects children, but not adults against tuberculosis. BCG evades phagosome maturation, autophagy, and reduces MHC-II expression of antigen-presenting cells (APCs) affecting T-cell activation. To bypass these defects, an autophagy-inducing, TLR-2 activating C5 peptide from Mtb-derived CFP-10 protein was overexpressed in BCG in combination with Ag85B. Recombinant BCG85C5 induced a robust MHC-II-dependent antigen presentation to CD4 T cells in vitro, and elicited stronger TH1 cytokines (IL-12, IL-1ß, and TNFα) from APCs of C57Bl/6 mice increasing phosphorylation of p38MAPK and ERK. BCG85C5 also enhanced MHC-II surface expression of MΦs by inhibiting MARCH1 ubiquitin ligase that degrades MHC-II. BCG85C5 infected APCs from MyD88 or TLR-2 knockout mice showed decreased antigen presentation. Furthermore, BCG85C5 induced LC3-dependent autophagy in macrophages increasing antigen presentation. Consistent with in vitro effects, BCG85C5 markedly expanded both effector and central memory T cells in C57Bl/6 mice protecting them against both primary aerosol infection with Mtb and reinfection, but was less effective among TLR-2 knockout mice. Thus, BCG85C5 induces stronger and longer lasting immunity, and is better than BCG against tuberculosis of mice.

Mesenchymal stem cells internalize Mycobacterium tuberculosis through scavenger receptors and restrict bacterial growth through autophagy.

Human mesenchymal stem cells (MSCs) express scavenger receptors that internalize lipids, including oxidized low-density lipoprotein (oxLDL). We report that MSCs phagocytose Mycobacterium tuberculosis (Mtb) through two types of scavenger receptors (SRs; MARCO and SR-B1), as blockade of the receptors with antibodies or siRNA knockdown decreased the uptake of Mtb. MSCs also expressed mannose receptor (MR) that was found to endocytose rhodamine-labeled mannosylated BSA (rMBSA), though the receptor was not involved in the uptake of Mtb. Dil-oxLDL and rMBSA taken up into MSC endosomes colocalized with Mtb phagosomes, thus suggesting that the latter were fusion competent. Phagocytosed Mtb did not replicate within MSCs, thus suggesting an intrinsic control of bacterial growth. Indeed, MSCs exhibited intrinsic autophagy, which was up-regulated after activation with rapamycin. SiRNA knockdown of autophagy initiator beclin-1 enhanced Mtb survival, whereas rapamycin-induced autophagy increased intracellular killing of Mtb. In addition, MSCs secreted nitric oxide after Mtb infection, and inhibition of NO by N(G)-monomethyl-L-arginine enhanced intracellular survival of Mtb. MSCs can be grown in large numbers in vitro, and autologous MSCs transfused into tuberculosis patients have been found to be safe and improve lung immunity. Thus, MSCs are novel phagocytic cells with a potential for immunotherapy in treating multidrug-resistant tuberculosis.

Development of a Model System to Evaluate Local Recurrence in Osteosarcoma and Assessment of the Effects of Bone Morphogenetic Protein-2.

PURPOSE: It is increasingly relevant to better define what constitutes an adequate surgical margin in an effort to improve reconstructive longevity and functional outcomes following osteosarcoma surgery. In addition, nonunion remains a challenging problem in some patients following allograft reconstruction. Bone morphogenetic protein-2 (BMP-2) could enhance osseous union, but has been historically avoided due to concerns that it may promote tumor recurrence. EXPERIMENTAL DESIGN: An orthotopic xenograft murine model was utilized to describe the natural temporal course of osteosarcoma growth. Tumors were treated either with surgery alone, surgery and single-agent chemotherapy, or surgery and dual-agent chemotherapy to assess the relationship between surgical margin and local recurrence. The effect of BMP-2 on local recurrence was similarly assessed. RESULTS: Osteosarcoma tumor growth was categorized into reproducible phases. Margins greater than 997 µm resulted in local control following surgery alone. Margins greater than 36 µm resulted in local control following surgery and single-agent chemotherapy. Margins greater than 12 µm resulted in local control following surgery and dual-agent chemotherapy. The application of exogenous BMP-2 does not confer an increased risk of local recurrence. CONCLUSIONS: This model reliably reproduces the clinical, radiographic, and surgical conditions encountered in human osteosarcoma. It successfully incorporates relevant chemotherapy, further paralleling the human experience. Surgical margins required to achieve local control in osteosarcoma can be reduced using single-agent chemotherapy and further decreased using dual-agent chemotherapy. The application of BMP-2 does not increase local recurrence in this model.

TCA cycle-mediated generation of ROS is a key mediator for HeR-MRSA survival under ß-lactam antibiotic exposure.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major multidrug resistant pathogen responsible for several difficult-to-treat infections in humans. Clinical Hetero-resistant (HeR) MRSA strains, mostly associated with persistent infections, are composed of mixed cell populations that contain organisms with low levels of resistance (hetero-resistant HeR) and those that display high levels of drug resistance (homo-resistant HoR). However, the full understanding of ß-lactam-mediated HeR/HoR selection remains to be completed. In previous studies we demonstrated that acquisition of the HoR phenotype during exposure to ß-lactam antibiotics depended on two key elements: (1) activation of the SOS response, a conserved regulatory network in bacteria that is induced in response to DNA damage, resulting in increased mutation rates, and (2) adaptive metabolic changes redirecting HeR-MRSA metabolism to the tricarboxylic acid (TCA) cycle in order to increase the energy supply for cell-wall synthesis. In the present work, we identified that both main mechanistic components are associated through TCA cycle-mediated reactive oxygen species (ROS) production, which temporally affects DNA integrity and triggers activation of the SOS response resulting in enhanced mutagenesis. The present work brings new insights into a role of ROS generation on the development of resistance to ß-lactam antibiotics in a model of natural occurrence, emphasizing the cytoprotective role in HeR-MRSA survival mechanism.

Exposure of clinical MRSA heterogeneous strains to ß-lactams redirects metabolism to optimize energy production through the TCA cycle.

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as one of the most important pathogens both in health care and community-onset infections. The prerequisite for methicillin resistance is mecA, which encodes a ß-lactam-insensitive penicillin binding protein PBP2a. A characteristic of MRSA strains from hospital and community associated infections is their heterogeneous expression of resistance to ß-lactam (HeR) in which only a small portion (≤ 0.1%) of the population expresses resistance to oxacillin (OXA) ≥ 10 µg/ml, while in other isolates, most of the population expresses resistance to a high level (homotypic resistance, HoR). The mechanism associated with heterogeneous expression requires both increase expression of mecA and a mutational event that involved the triggering of a ß-lactam-mediated SOS response and related lexA and recA genes. In the present study we investigated the cellular physiology of HeR-MRSA strains during the process of ß-lactam-mediated HeR/HoR selection at sub-inhibitory concentrations by using a combinatorial approach of microarray analyses and global biochemical profiling employing gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) to investigate changes in metabolic pathways and the metabolome associated with ß-lactam-mediated HeR/HoR selection in clinically relevant heterogeneous MRSA. We found unique features present in the oxacillin-selected SA13011-HoR derivative when compared to the corresponding SA13011-HeR parental strain that included significant increases in tricarboxyl citric acid (TCA) cycle intermediates and a concomitant decrease in fermentative pathways. Inactivation of the TCA cycle enzyme cis-aconitase gene in the SA13011-HeR strain abolished ß-lactam-mediated HeR/HoR selection demonstrating the significance of altered TCA cycle activity during the HeR/HoR selection. These results provide evidence of both the metabolic cost and the adaptation that HeR-MRSA clinical strains undergo when exposed to ß-lactam pressure, indicating that the energy production is redirected to supply the cell wall synthesis/metabolism, which in turn contributes to the survival response in the presence of ß-lactam antibiotics.

Targeting of PBP1 by ß-lactams determines recA/SOS response activation in heterogeneous MRSA clinical strains.

The SOS response, a conserved regulatory network in bacteria that is induced in response to DNA damage, has been shown to be associated with the emergence of resistance to antibiotics. Previously, we demonstrated that heterogeneous (HeR) MRSA strains, when exposed to sub-inhibitory concentrations of oxacillin, were able to express a homogeneous high level of resistance (HoR). Moreover, we showed that oxacillin appeared to be the triggering factor of a ß-lactam-mediated SOS response through lexA/recA regulators, responsible for an increased mutation rate and selection of a HoR derivative. In this work, we demonstrated, by selectively exposing to ß-lactam and non-ß-lactam cell wall inhibitors, that PBP1 plays a critical role in SOS-mediated recA activation and HeR-HoR selection. Functional analysis of PBP1 using an inducible PBP1-specific antisense construct showed that PBP1 depletion abolished both ß-lactam-induced recA expression/activation and increased mutation rates during HeR/HoR selection. Furthermore, based on the observation that HeR/HoR selection is accompanied by compensatory increases in the expression of PBP1,-2, -2a, and -4, our study provides evidence that a combination of agents simultaneously targeting PBP1 and either PBP2 or PBP2a showed both in-vitro and in-vivo efficacy, thereby representing a therapeutic option for the treatment of highly resistant HoR-MRSA strains. The information gathered from these studies contributes to our understanding of ß-lactam-mediated HeR/HoR selection and provides new insights, based on ß-lactam synergistic combinations, that mitigate drug resistance for the treatment of MRSA infections.

ß-Lactams increase the antibacterial activity of daptomycin against clinical methicillin-resistant Staphylococcus aureus strains and prevent selection of daptomycin-resistant derivatives.

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged to be one of the most important pathogens both in health care and in community-onset infections. Daptomycin (DAP) is a cyclic anionic lipopeptide recommended for treatment of skin infections, bacteremia, and right-sided endocarditis caused by MRSA. Resistance to DAP (DAP(r)) has been reported in MRSA and is mostly accompanied by a parallel decrease in oxacillin resistance, a process known as the "seesaw effect." Our study provides evidence that the seesaw effect applies to other ß-lactams and carbapenems of clinical use, including nafcillin (NAF), cefotaxime (CTX), amoxicillin-clavulanic (AMC), and imipenem (IMP), in heterogeneous DAP(r) MRSA strains but not in MRSA strains expressing homogeneous ß-lactam resistance. The antibacterial efficacy of DAP in combination with ß-lactams was evaluated in isogenic DAP-susceptible (DAP(s))/Dap(r) MRSA strains originally obtained from patients that failed DAP monotherapy. Both in vitro (MIC, synergy-kill curve) and in vivo (wax worm model) approaches were used. In these models, DAP and a ß-lactam proved to be highly synergistic against both heterogeneous and homogeneous clinical DAP(r) MRSA strains. Mechanistically, ß-lactams induced a reduction in the cell net positive surface charge, reverting the increased repulsion provoked by DAP alone, an effect that may favor the binding of DAP to the cell surface. The ease of in vitro mutant selection was observed when DAP(s) MRSA strains were exposed to DAP. Importantly, the combination of DAP and a ß-lactam prevented the selection of DAP(r) variants. In summary, our data show that the DAP-ß-lactam combination may significantly enhance both the in vitro and in vivo efficacy of anti-MRSA therapeutic options against DAP(r) MRSA infections and represent an option in preventing DAP(r) selection in persistent or refractory MRSA infections.

Telescopic mating technique for bulk allograft reconstruction.

Bulk allograft reconstruction plays an important role in limb-salvage reconstructive surgery but is complicated by nonunion in up to one-third of cases. Because allograft-host healing is mediated via creeping substitution, intimate bone contact is desirable. Intraoperative assessment and optimization of the allograft-host junction site using a conventional transverse osteotomy is challenging and may result in slight gapping. Speculatively, this may result in longer healing times and may contribute to the high rate of non-union. Minimizing the nonunion rate and time to union are of value. This article describes the telescopic mating technique, which allows for substantially greater bone contact across the allograft-host junction site.

Cutting edge: Nicastrin and related components of γ-secretase generate a peptide epitope facilitating immune recognition of intracellular mycobacteria, through MHC class II-dependent priming of T cells.

Bacillus Calmette-Guérin (BCG), the antituberculosis vaccine, localizes within immature phagosomes of macrophages and dendritic cells (APCs), and avoids lysosomal degradation. BCG-derived antigenic peptides are thus inefficiently processed by APCs, and we investigated alternate mechanisms of Ag processing. Proteomics identified that BCG phagosomes are enriched for nicastrin, APH, and presenilin components of γ-secretase, a multimeric protease. Using an in vitro Ag presentation assay and BCG-infected APCs, we found γ-secretase components to cleave BCG-derived Ag85B to produce a peptide epitope, which, in turn, primed IL-2 release from Ag85B-specific T cell hybridoma. siRNA knockdown or chemical inhibition of γ-secretase components using L685458 decreased the ability of BCG or Mycobacterium tuberculosis-infected APCs to present Ag85B. In addition, L685485 inhibition of γ-secretase led to a decreased ability of BCG-dendritic cells to immunize mice and induce Ag85B-specific CD4 T cells in vivo. Because BCG and M. tuberculosis sequester within APCs preventing immune recognition, γ-secretase components appear to fortuitously process the immunodominant Ag85B, facilitating immune recognition.

Outcomes after the arthroscopic treatment of femoroacetabular impingement in a mixed group of high-level athletes.

BACKGROUND: Femoroacetabular impingement has become more widely recognized in the athletic patient population. The purpose of the present study was to review the clinical outcome after arthroscopic treatment of femoroacetabular impingement in a mixed population of high-level athletes. HYPOTHESIS: Arthroscopic treatment of femoroacetabular impingement results in significant improvement in clinical outcome and a high rate of return to play. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: High-level athletes who underwent arthroscopic treatment of femoroacetabular impingement (rim trimming, labral refixation or debridement, femoral osteochondroplasty) with a minimum of 1-year follow-up were retrospectively identified. All patients completed hip-specific outcome scores (Modified Harris Hip Score [MHHS] and Hip Outcome Score [HOS]) at baseline and most recent follow-up. RESULTS: Forty-seven patients with an average age of 22.8 ± 6.2 years met the study criteria with a mean follow-up of 27.0 ± 5.5 months. Thirty-three patients (70.2%) were available for follow-up. The level of competition was 27.7% varsity high school, 53.2% college, and 19.1% professional athletes. There were statistically significant improvements in the mean MHHS score (preoperative, 68.6 ± 12.8; postoperative, 88.5 ± 17.7; P = .002) as well as the HOS score (preoperative, 78.8 ± 11.3; postoperative, 91.4 ± 14.0; P = .03). There was a significant improvement in the alpha angle, with 76.4° ± 14.5° preoperatively and 51.4° ± 11.7° postoperatively (P = .0003). Seventy-nine percent of patients were able to return to play after hip arthroscopy at a mean of 9.4 ± 4.7 months (range, 4-26 months); of those patients, 92.3% were able to return to the same level of competition. At 2-year follow-up, 73% of patients were able to return to play. CONCLUSION: Arthroscopic treatment of femoroacetabular impingement in a mixed group of high-level athletes may result in a significant improvement in hip functional outcome: 78% of athletes were able to return to play at 1 year and 73% of athletes were able to play at 2-year follow-up.

Label-free proteomics and systems biology analysis of mycobacterial phagosomes in dendritic cells and macrophages.

Proteomics has been applied to study intracellular bacteria and phagocytic vacuoles in different host cell lines, especially macrophages (Mφs). For mycobacterial phagosomes, few studies have identified over several hundred proteins for systems assessment of the phagosome maturation and antigen presentation pathways. More importantly, there has been a scarcity in publication on proteomic characterization of mycobacterial phagosomes in dendritic cells (DCs). In this work, we report a global proteomic analysis of Mφ and DC phagosomes infected with a virulent, an attenuated, and a vaccine strain of mycobacteria. We used label-free quantitative proteomics and bioinformatics tools to decipher the regulation of phagosome maturation and antigen presentation pathways in Mφs and DCs. We found that the phagosomal antigen presentation pathways are repressed more in DCs than in Mφs. The results suggest that virulent mycobacteria might co-opt the host immune system to stimulate granuloma formation for persistence while minimizing the antimicrobial immune response to enhance mycobacterial survival. The studies on phagosomal proteomes have also shown promise in discovering new antigen presentation mechanisms that a professional antigen presentation cell might use to overcome the mycobacterial blockade of conventional antigen presentation pathways.

Analysis of phagosomal proteomes: from latex-bead to bacterial phagosomes.

Phagosomal proteome characterization has contributed significantly to the understanding of host-pathogen interaction and the mechanism of infectious diseases caused by intracellular bacteria. The latex bead-containing phagosome has been widely used as a model system to study phagosomal proteomes at a global level. In contrast, the study of bacteria-containing phagosomes at a similar level has just begun. A number of intracellular microbial species are studied for their proteomes during the invasion of a host, providing insight into their metabolic adaptation in host cells and interaction with host-cell antimicrobial environments. In this review, we attempt to summarize the most recent advancements in the proteomic study of microbial phagosomes, especially those originating from mouse or human cells. We also briefly describe the proteomics of latex bead-containing phagosomes because they are often used as model phagosomes for study. We provide descriptions on major biological and technological components in phagosomal proteome studies. We also discuss the role of phagosomal proteome study in the broader horizon of systems biology and the technological challenges in phagosomal proteome characterization.

Intraocular pressure instability after 23-gauge vitrectomy.

PURPOSE: The purpose of this study was to describe outcomes, trends, risk factors, and protective factors for intraocular pressure (IOP) spikes in patients undergoing 23-gauge pars plana vitrectomy. METHODS: A retrospective review in an academic institution was performed on all eyes undergoing 23-gauge vitrectomy with at least 1-month follow-up. The main outcome measures included IOP and operative complications. RESULTS: Ninety-seven eyes of 93 patients were included. Intraocular pressure spikes >22 in the first month occurred in 73% of eyes with or suspect for glaucoma versus 46% of eyes without (P = 0.017); 76% of eyes with a gas fill versus 44% of eyes with a fluid fill (P = 0.0036); and 21% of eyes started on IOP-lowering drops on postoperative day 1 versus 49% of eyes who were not (P = 0.0033). Complications included retinal tears (3%), intraoperative retinal detachment (2%), and postoperative retinal detachment (2%). Fifteen percent of eyes required suturing of at least one sclerotomy. There were no cases of postoperative hypotony or endophthalmitis. CONCLUSION: Patients with or suspect for glaucoma or those with a gas fill may be at risk for high postoperative IOP during the first month. Aggressive early treatment of IOP may prevent IOP spikes in the early postoperative period.

Toll-like receptor 2 ligand-induced protection against bacterial endophthalmitis.

BACKGROUND: Activation of innate immunity plays a key role in determining the outcome of an infection. Here, we investigated whether Toll-like receptors (TLRs) are involved in retinal innate response and explored the prophylactic use of TLR2 ligand in preventing bacterial endophthalmitis. METHODS: C57BL/6 mice were given intravitreal injections of Pam3Cys, a synthetic ligand of TLR2, or vehicle (phosphate-buffered saline) 24 h prior to Staphylococcus aureus inoculation. The severity of endophthalmitis was graded by slit lamp, electroretinography, histological examinations, and determination of bacterial load in the retina. The expression of cytokines/chemokines and cathelicidin-related antimicrobial peptide was assessed by enzyme-linked immunosorbent assay and Western blot, respectively. RESULTS: Intravitreal injections of Pam3Cys up-regulated TLR2 expression in the retina of C57BL/6 mice, and Pam3Cys pretreatment significantly improved the outcome of S. aureus endophthalmitis, preserved retinal structural integrity, and maintained visual function as assessed by electroretinography in C57BL/6 mice. Furthermore, Pam3Cys pretreatment activated retinal microglia cells, induced the expression of cathelicidin-related antimicrobial peptide, and remarkably reduced the bacterial load. CONCLUSIONS: This is the first report that highlights the existence and role of TLR2 in retinal innate immune response to S. aureus infection and suggests that modulation of TLR activation provides a novel prophylactic approach to prevent bacterial endophthalmitis.