High CO2 Levels Impair Lung Wound Healing.

Delayed lung repair leads to alveolopleural fistulae, which are a major cause of morbidity after lung resections. We have reported that intrapleural hypercapnia is associated with delayed lung repair after lung resection. Here, we provide new evidence that hypercapnia delays wound closure of both large airway and alveolar epithelial cell monolayers because of inhibition of epithelial cell migration. Cell migration and airway epithelial wound closure were dependent on Rac1-GTPase activation, which was suppressed by hypercapnia directly through the upregulation of AMP kinase and indirectly through inhibition of injury-induced NF-κB-mediated CXCL12 (pleural CXC motif chemokine 12) release, respectively. Both these pathways were independently suppressed, because dominant negative AMP kinase rescued the effects of hypercapnia on Rac1-GTPase in uninjured resting cells, whereas proteasomal inhibition reversed the NF-κB-mediated CXCL12 release during injury. Constitutive overexpression of Rac1-GTPase rescued the effects of hypercapnia on both pathways as well as on wound healing. Similarly, exogenous recombinant CXCL12 reversed the effects of hypercapnia through Rac1-GTPase activation by its receptor, CXCR4. Moreover, CXCL12 transgenic murine recipients of orthotopic tracheal transplantation were protected from hypercapnia-induced inhibition of tracheal epithelial cell migration and wound repair. In patients undergoing lobectomy, we found inverse correlation between intrapleural carbon dioxide and pleural CXCL12 levels as well as between CXCL12 levels and alveolopleural leak. Accordingly, we provide first evidence that high carbon dioxide levels impair lung repair by inhibiting epithelial cell migration through two distinct pathways, which can be restored by recombinant CXCL12.

Three techniques for guidewire-assisted sulcus glaucoma tube shunt placement.

Purpose: Tube shunts can be inserted into the anterior chamber, ciliary sulcus, or pars plana. Sulcus tube placement can be challenging. This report demonstrates three techniques for guidewire-assisted sulcus tube insertion. Observations: The first technique uses a needle inserted through a paracentesis 180-degrees across from the tube entry site and creates an ab-interno sclerotomy through which the guidewire is inserted by docking it into the needle bevel. The second technique involves inserting the guidewire into the eye via a paracentesis and using microforceps to retrieve it through a sclerotomy. The third technique uses forceps to insert the guidewire into a paracentesis 180° across from the planned tube entry site and dock it into a needle bevel that has been inserted into the sulcus. Each of these techniques provides a reliable and reproducible way to insert a tube into the sulcus. Conclusions and importance: Guidewire-assisted tube entry offers a promising solution in cases of difficult sulcus tube placement without substantial additional cost.

Baerveldt-350 with adjunctive goniotomy: Pilot results.

Purpose: To describe a previously unreported method for optimizing early intraocular pressure-lowering in non-valved aqueous shunt surgery, and to report pilot results from a case series. Observations: We report pilot results of 30 eyes that underwent Baerveldt-350 implantation with adjunctive goniotomy, in addition to 3 needle-puncture fenestrations, to enhance intraocular pressure lowering and facilitate higher steroid dosing before spontaneous ligature dissolution. Conclusions and Importance: In patients with open-angle glaucoma, goniotomy is a safe and effective procedure when performed in conjunction with non-valved glaucoma tube shunt implantation.

Gonioscopy-assisted transluminal trabeculotomy in neovascular glaucoma: Salvaging the conventional outflow pathway.

Purpose: To report a case of acute neovascular glaucoma with partial synechial angle closure secondary to central retinal vein occlusion that underwent gonioscopy-assisted transluminal trabeculotomy as well as near-monthly anti-vascular endothelial growth factor (VEGF) injections and panretinal photocoagulation (PRP) treatments. Observations: Nine months after GATT, the patient had achieved intraocular pressure control on no medications. However, she was lost to follow up for 4 months and received no anti-VEGF or PRP during that time; she re-presented with acute NVG and complete synechial closure, and ultimately underwent aqueous shunt implantation. Conclusions and Importance: To our knowledge, this is the first reported attempt of an ab interno angle surgery to successfully restore aqueous outflow through the conventional outflow pathway in an eye with acute NVG and partial synechial angle closure. We posit that this can be an effective approach to achieve IOP control in NVG with at least partially open angles, as long as sufficient anti-neovascular treatments are administered until the underlying neovascular drive achieves quiescence.

Tonsillar Helicobacter pylori colonization in chronic tonsillitis: systematic review and meta-analysis.

IMPORTANCE: Helicobacter pylori colonization contributes significantly to multiple disease states, but its role in the development of tonsillar infection is unclear. Understanding the causes of chronic tonsillitis is important in clinical decision making of this commonly treated disease. OBJECTIVE: To assess the correlation between H pylori colonization of tonsillar tissue in chronic tonsillitis and in noninfectious hyperplastic tonsils. DATA SOURCES: We searched PubMed, MEDLINE, the Cochrane Trial Registry (through June 2014) and relevant article bibliographies. STUDY SELECTION: Systematic review and meta-analysis of studies assessing the correlation between H pylori colonization in tonsillar tissues of patients undergoing tonsillectomy for either chronic tonsillitis or noninfectious causes. Included studies hypothesized that H pylori played a role in the development of chronic tonsillitis. All included studies investigated the presence of H pylori in tonsillar tissue removed for various indications. Included studies must have used an accepted method of testing for H pylori. DATA EXTRACTION AND ANALYSIS: Studies were systematically reviewed by 2 independent reviewers for inclusion. Reported results of H pylori testing between tissues removed for infectious or noninfectious causes were systematically reviewed. The odds ratio of Hpylori colonization in tissue removed for chronic tonsillitis compared with tissue removed for noninfectious causes was calculated using a random-effects model. RESULTS: Six studies met inclusion criteria and had suitable data for pooling (n = 436). Of these, 2 studies measured H pylori colonization of tonsillar tissue in pediatric populations. One study analyzed tissue in both adult and pediatric populations. Noninfectious indications for tonsillectomy included sleep apnea or sleep-related breathing disorder, obstruction, carcinoma, and tonsillar hypertrophy. Overall, tonsillar H pylori colonization was found not to be significantly present more often in tissue samples removed secondary to recurrent infection rather than to noninfectious indications. The odds ratio of H pylori colonization in the tonsils of patients with chronic tonsillitis was 1.993 (95% CI, 0.909-4.371) (P = .09). CONCLUSIONS AND RELEVANCE: Helicobacter pylori colonization was not found to be more prevalent on tonsillar tissue with chronic or recurrent infections. The reviewed studies provide no evidence that H pylori infection plays a role in the pathogenesis or development of chronic tonsillitis.

Decreased CXCL12 is associated with impaired alveolar epithelial cell migration and poor lung healing after lung resection.

BACKGROUND: Prolonged air leak (PAL) is an important cause of morbidity and mortality after lung resection, but its pathogenesis has not been elucidated. Migration of alveolar type II epithelial cells is essential for lung wound repair. Here we determined the role of C-X-C motif chemokine 12 (CXCL12) on alveolar epithelial cell migration and lung wound healing. METHODS: CXCL12 in the pleural fluid of patients was analyzed using enzyme-linked immunosorbent assay. Human A549 and murine MLE12 alveolar epithelial cell lines were used for wound closure, cell migration, and proliferation assays. Western blot was used to analyze Rac1 and cofilin. RESULTS: Pleural CXCL12 was decreased in patients with PAL (1,389 ± 192 vs 3,270 ± 247 pg/mL; P < .0001). CXCL12 enhanced scratch wound closure in both A549 (77.9 ± 0.7% vs 71.5 ± 0.4%; P = .0016) and MLE12 (92.9 ± 4.9% vs 66.0 ± 4.8%; P = .017). CXCL12 enhanced migration by 57% in A549 (P = .0008) and by 86% in MLE12 (P < .0001). AMD3100, a selective CXCR4 antagonist, prevented the effects of CXCL12. CXCL12 increased Rac1 and cofilin activation but did not change bromodeoxyuridine incorporation or cell counts. CONCLUSION: Reduced pleural CXCL12 is associated with PAL. CXCL12 promotes alveolar epithelial cell migration by binding to its receptor CXCR4 and may have a role in lung healing. CXCL12-mediated alveolar epithelial cell migration is associated with Rac1 and cofilin activation.