MERCURY-3: a randomized comparison of netarsudil/latanoprost and bimatoprost/timolol in open-angle glaucoma and ocular hypertension.

PURPOSE   : To compare the efficacy and safety of the fixed-dose combination (FDC) of netarsudil 0.02%/latanoprost 0.005% ophthalmic solution (NET/LAT; Roclanda®) with bimatoprost 0.03%/timolol maleate 0.5% (BIM/TIM; Ganfort®) ophthalmic solution in the treatment of open-angle glaucoma (OAG) and ocular hypertension (OHT). METHODS: MERCURY-3 was a 6-month prospective, double-masked, randomized, multicenter, active-controlled, parallel-group, non-inferiority study. Patients (≥ 18 years) with a diagnosis of OAG or OHT in both eyes that was insufficiently controlled with topical medication (IOP ≥ 17 mmHg in ≥ 1 eye and < 28 mmHg in both eyes) were included. Following washout, patients were randomized to once-daily NET/LAT or BIM/TIM for up to 6 months; efficacy was assessed at Week 2, Week 4, and Month 3; safety was evaluated for 6 months. Comparison of NET/LAT relative to BIM/TIM for mean IOP at 08:00, 10:00, and 16:00 h was assessed at Week 2, Week 6, and Month 3. Non-inferiority of NET/LAT to BIM/TIM was defined as a difference of ≤ 1.5 mmHg at all nine time points through Month 3 and ≤ 1.0 mmHg at five or more of nine time points through Month 3. RESULTS: Overall, 430 patients were randomized (NET/LAT, n = 218; BIM/TIM, n = 212), and all received at least one dose of study medication. Efficacy analyses were performed at Month 3 on 388 patients (NET/LAT, n = 184; BIM/TIM, n = 204). NET/LAT demonstrated non-inferiority to BIM/TIM, with a between-treatment difference in IOP of ≤ 1.5 mmHg achieved at all time points and ≤ 1.0 mmHg at the majority of time points (six of nine) through Month 3. Mean diurnal IOP during the study ranged from 15.4 to 15.6 mmHg and 15.2 to 15.6 mmHg in the NET/LAT and BIM/TIM groups respectively, with no between-group statistically significant difference. No significant differences were observed in key secondary endpoints. No serious, treatment-related adverse events (AEs) were observed, and AEs were typically mild/moderate in severity. The most common treatment-related AEs were conjunctival hyperemia (NET/LAT, 30.7%; BIM/TIM, 9.0%) and cornea verticillata (NET/LAT, 11.0%; BIM/TIM, 0%). CONCLUSIONS: Once-daily NET/LAT was non-inferior to BIM/TIM in IOP reduction in OAG and OHT, with AEs consistent with previous findings. NET/LAT offers a compelling alternative FDC treatment option for OAG and OHT.

The Thickness of the Retinal Nerve Fiber Layer (RNFL) as a Biomarker in Uveitis.

AIMS: To study the changes of the retinal nerve fiber layer (RNFL) thickness during and following uveitis flares. METHODS: This was a retrospective study of patients with uveitis diagnosed in the ophthalmology service of Torrevieja hospital. We analyzed RNFL thickness during and after the acute episode. RESULTS: We included 29 patients. Most patients (55.2%) had anterior uveitis; followed by posterior, intermediate and panuveitis. Mean RNFL thickness was significantly higher during the flare (132.17±35.54µm vs 107.66±17.10µm). RNFL thickness had no difference between groups with or without macular edema. CONCLUSIONS: The RNFL thickens during flares in most patients with uveitis. It can be measured by optical coherence tomography in a non-invasive way, representing an objective marker of inflammation. This can favor earlier detection of flares, resolution, and recurrence of uveitis. More studies are needed to determine the evolution of RNFL over time and in different types of uveitis.

Costs and Healthcare Resource Utilization Associated with Posterior Capsule Opacification After Cataract Surgery with Five Different Intraocular Lenses: An Economic Analysis for Spain.

Purpose: To estimate the economic impact of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy and its related complications for five different intraocular lenses (IOLs) from the payer and hospital perspectives in Spain. Materials and Methods: The three-year incidence rates of Nd:YAG laser capsulotomy after cataract surgery with five different single-piece acrylic monofocal IOLs (AcrySof IOLs, AJL LLASY60, IOL Tech Stabibag, Medicontur Bi-flex, Zeiss Asphina) for 8293 patients were derived from odds ratios of multivariate analysis adjusted for age, gender, and diabetic retinopathy. A cost-consequence model for a hypothetical cohort of 2000 eyes was then developed to quantify the potential impact of Nd:YAG capsulotomy in terms of costs and time for each of the included IOLs, from the payer and hospital perspectives. Results: The adjusted three-year Nd:YAG laser capsulotomy incidence was 5.0% (95% CI 3.9 to 6.1) for AcrySof and ranged from 26.0% to 44.0% for the other four IOLs. The average costs of Nd:YAG treatment and related complications were €261.90 for payers and €19.99 for hospitals. The average time needed for Nd:YAG treatment and related complications was 32.82 minutes. Model estimates based on 2000 hypothetical cataract surgeries showed that AcrySof IOLs could lead to cost savings between €110,259.90 and €205,591.50 for payers. For hospitals, time, and cost savings with AcrySof ranged from 230.29 hours and €8415.79 compared to Zeiss Asphina to 429.40 hours and €15,692.15 compared to AJL LLASY60 IOLs. Conclusion: Post cataract surgery, AcrySof IOLs were associated with a significantly lower incidence of Nd:YAG treatment and its subsequent complications compared to other IOLs. Our analysis shows that IOL choice is an important factor that can reduce the burden for patients, payers, and hospitals.

Nd:YAG capsulotomy incidence associated with five different single-piece monofocal intraocular lenses: a 3-year Spanish real-world evidence study of 8293 eyes.

OBJECTIVES: To investigate the associations between different single-piece monofocal intraocular lenses (IOLs) and neodymium-doped yttrium aluminum garnet laser (Nd:YAG) capsulotomy incidence 3 years after cataract surgery in a Spanish cohort. METHODS: This is a longitudinal retrospective cohort study. Data were extracted from the electronic medical records of two large regional hospitals in Spain. Patients aged ≥65 years receiving cataract surgery with placement of five different IOLs and with ≥6 months of baseline data were included. We report the Nd:YAG capsulotomy incidence 3 years post cataract surgery, and the survival plot over the 3 years of follow-up time. The associated adjusted (age, gender, and diabetic retinopathy) multivariate analysis with odds ratios (ORs) and 95% CIs is also presented. RESULTS: The cohort (53% female, mean age 75 ± 5.9 years) included 14,519 eyes (Alcon AcrySof = 2968, AJL LLASY60 = 1776, Medicontur Bi-flex = 5176, Zeiss Asphina = 4478, and IOL Tech Stabibag = 121). Of these, 8293 were retained until 3-year follow-up. At 3 years after cataract surgery, the Nd:YAG capsulotomy incidence was 5% for Alcon AcrySof, while it ranged from 21.2% to 31.1% for the other IOLs (p < 0.0001 for each comparison). The odds for Nd:YAG capsulotomy were significantly higher (p < 0.0001) for other IOLs compared with those of Alcon AcrySof (ORs = 8.85, 5.86, 5.74, 5.21 for AJL LLASY60, Medicontur Bi-flex, IOL Tech Stabibag, and Zeiss Asphina, respectively). CONCLUSIONS: The lower Nd:YAG capsulotomy rates for Alcon AcrySof IOLs compared to the other IOLs support the importance of lens choice in reducing patient burden and treatment costs.

Intraspecific virulence of entomopathogenic nematodes against the pests Frankliniella occidentalis (Thysanoptera: Thripidae) and Tuta absoluta (Lepidoptera: Gelechiidae).

Entomopathogenic nematodes (EPN) are excellent biocontrol agents against various insect pests. Novel biotechnological approaches can enhance their utility against insects above-ground, opening a new venue for selecting superior EPN against certain insects. We hypothesize that different populations of the same species but from different origins (habitat, ecoregion) will differ in their virulence. This study aimed to evaluate the virulence of various EPN populations against two pests of worldwide incidence and damage to high value crops: Frankliniella occidentalis (Thysanoptera: Thripidae) and Tuta absoluta (Lepidoptera: Gelechiidae). We tested 10 EPN populations belonging to three EPN species: Heterorhabditis bacteriophora (Koppert, MG-618b, AM-203, RM-102), Steinernema feltiae (Koppert, RS-5, AM-25, RM-107), and Steinernema carpocapsae (Koppert, MG-596a). Each EPN population was tested at two concentrations. Frankliniella occidentalis was tested at 160 and 80 IJs/cm2 and T. absoluta at 21 and 4 IJs/cm2. Control treatments followed the same experimental procedure but only adding distilled water. Overall, whenever different, higher IJs concentration resulted in lower adult emergence, higher larval mortality, and shorter time to kill the insects. Considering the low concentration, S. feltiae provided the best results for both insects and instars investigated, while H. bacteriophora and S. carpocapsae required a high concentration to reach similar or slightly better results. Differences among populations of each of the species were detected, but only the native populations of H. bacteriophora populations showed consistently higher control values against both insects/instar compared with the commercial one. Differences among S. feltiae and S. carpocapsae populations depended on the IJs concentration, insect, and instar. We consider S. feltiae a very promising species for their application against F. occidentalis and T. absoluta, with the Koppert population as the most consistent among the populations tested. Specific EPN-populations of S. carpocapsae and H. bacteriophora were good candidates against certain instar/insects at high concentrations. This study emphasized the importance of intraspecific variability for EPN virulence.

Long-Term Clinically Significant Posterior Capsular Opacification Development Pattern in Eyes Implanted with an Aspheric Monofocal Intraocular Lens with a Square Optic Edge.

PURPOSE: To analyse the posterior capsular opacification (PCO) development pattern in the long term in eyes implanted with a monofocal intraocular lens (IOL) with a square edge all around the optic. METHODS: Longitudinal retrospective study is data analyzed from a total of 7059 eyes from 4764 patients (mean age: 75.8 years) undergoing cataract surgery with implantation of an aspheric monofocal IOL (Bi-Flex HL 677AB/677P, Medicontur, Budapest, Hungary). These data were retrospectively collected using the electronic medical record of the hospitals involved. Nd : YAG capsulotomy rates were calculated per year during a follow-up of more than 10 years. The Kaplan-Meier analysis was used to establish the transparent capsule survival rate. RESULTS: The Nd : YAG capsulotomy rate increased from 1.1% at 1 year postoperatively to 17.2% at 5 years after surgery. No significant differences were found between eyes with and without capsulotomy in terms of age (p = 0.202), gender (p = 0.061), type of anaesthesia used (p = 0.128), and presence of conditions such as hard cataract (p = 0.111) or pseudoexfoliation (p = 0.137). IOL power was significantly lower in those eyes of patients requiring Nd : YAG capsulotomy during the follow-up (p < 0.001). Significantly more eyes implanted with the preloaded model of the IOL required capsulotomy (p < 0.001). Mean survival time and rate were 9.38 years and 85.9%, respectively. CONCLUSIONS: Most eyes undergoing cataract with implantation of the Bi-Flex IOL do not develop a clinically significant PCO requiring Nd : YAG capsulotomy in the long term. IOL material and design may be the main factors accounting for this finding.

What to do when the parathyroid gland is not found during a transcervical exploration?

The most frequent cause of suboptimal results in a parathyroid adenoma resection is an ectopic location, mainly in the anterior mediastinum. These cases may not always be resected through a traditional cervical access. We present 2 cases of primary hyperparathyroidism who underwent an unsuccessful bilateral cervical exploration due to parathyroid tissue located inside the thymic gland. A video-assisted thoracoscopic surgery thymectomy with intraoperative determination of blood parathormone levels was performed. A 50% reduction of intraoperatory parathyroid hormone blood from the highest basal level at 5 and 10 min after resection was obtained. Final pathological results showed an intra-thymic parathyroid adenoma in the first patient and an intra-thymic focus of parathyroid hyperplasia in the second patient. In conclusion, video-assisted thoracoscopic surgery thymectomy could be the optimal approach to resect ectopic parathyroid adenomas located in the anterior mediastinum.

Supraciliary versus intrascleral implantation with hema implant (Esnoper V-2000) in deep sclerectomy: a multicenter randomized controlled trial.

PURPOSE: To compare the supraciliary versus intrascleral implantation of the hema implant (Esnoper V-2000) in terms of the efficacy and safety in nonpenetrating deep sclerectomy (NPDS). PATIENTS AND METHODS: Prospective, randomized, unmasked, competitive and multicenter clinical trial. Eighty-three eyes from 83 patients suffering from open-angle glaucoma (40 males, 43 females) were enrolled and followed up for 12 months. Main outcome measures were best-corrected visual acuity (BCVA), intraocular pressure (IOP), perimetry (mean defect, MD and Visual Field Index, VFI), pachymetry, number of antiglaucoma medications and analysis of blebs according Moorfields Bleb Grading. RESULTS: The IOP was significantly reduced in both groups from 23.74 ± 6.9 mmHg (implant sutured to the sclera, group 1) and 23.46 ± 6.47 mmHg (implant placed in the suprachoroidal space, group 2) to 15.43 ± 4.27 mmHg (p < 0.001) and 14.62 ± 3.64 mmHg (p < 0.001), respectively. There were no statistically significant differences in mean IOP values between the groups a year after the surgery (p = 0.581). BCVA did not show statistical differences in comparison with baseline (p = 0.09, group 1; p = 0.42, group 2). The mean number of antiglaucoma medications was reduced in both groups from 2.58 ± 0.04 and 2.68 ± 0.02 before the surgery to 0.32 ± 0.76 and 0.24 ± 0.66 after surgery. CONCLUSION: Nonpenetrating deep sclerectomy using hema implant (Esnoper V-2000) is safe and effective regardless of the positioning of the implant. We achieved IOP decrease and reduction in antiglaucoma medications during the first year after surgery without significant differences between both techniques.

Optical Coherence Tomography in Children With Microtropia.

PURPOSE: To assess whether optical coherence tomography (OCT) could be useful for detecting and documenting fixation in patients with microtropia. METHODS: Retinal fixation observation was performed using spectral-domain OCT on amblyopic children with microtropia. The position between the retinal fixation point and the anatomical fovea was measured, in microns, using the system software tools. Only patients with a high level of cooperation, OCT scan quality signal of 7 or better, and visual acuity of 0.70 logarithm of the minimum angle of resolution (logMAR) or worse in the amblyopic eye were included. RESULTS: A total of 25 patients were included: 15 with microtropia (study group) and 10 without tropia and with foveal fixation and stereopsis (control group). In the study group, microtropia was previously diagnosed in 67% of cases through the cover test, and was predominantly in the left eye (73%). The average visual acuity of the sound eye was 0.03 decimal and 0.18 logMAR in the amblyopic eye. The microtropia was 3.73 ± 3.34 prism diopters and eccentric fixation (387 ± 199 µm) with OCT was observed in all cases except one. Eccentricity was predominantly in the superonasal quadrant (57%). Both eyes in the control group and the contralateral eyes of the study group showed foveal fixation. CONCLUSIONS: OCT can play an important role in the diagnosis and measurement of eccentric fixation in eyes with microtropia, providing high sensitivity. [J Pediatr Ophthalmol Strabismus. 2018;55(3):171-177.].

Prospective Evaluation of Two iStent® Trabecular Stents, One iStent Supra® Suprachoroidal Stent, and Postoperative Prostaglandin in Refractory Glaucoma: 4-year Outcomes.

INTRODUCTION: This study evaluates long-term outcomes of two trabecular micro-bypass stents, one suprachoroidal stent, and postoperative prostaglandin in eyes with refractory open angle glaucoma (OAG). METHODS: Prospective ongoing 5-year study of 80 eligible subjects (70 with 4-year follow-up) with OAG and IOP ≥ 18 mmHg after prior trabeculectomy and while taking 1-3 glaucoma medications. Subjects received two iStent® trabecular micro-bypass stents, one iStent Supra® suprachoroidal stent, and postoperative travoprost. Postoperative IOP was measured with medication and annually following medication washouts. Performance was measured by the proportion of eyes with ≥ 20% IOP reduction on one medication (the protocol-specified prostaglandin) versus preoperative medicated IOP (primary outcome); and the proportion of eyes with postoperative IOP ≤ 15 and ≤ 18 mmHg on one medication (secondary outcome). Additional clinical and safety data included medications, visual field, pachymetry, gonioscopy, adverse events, visual acuity, and slit-lamp and fundus examinations. RESULTS: Preoperatively, mean medicated IOP was 22.0 ± 3.1 mmHg on 1.2 ± 0.4 medications, and mean unmedicated IOP was 26.4 ± 2.4 mmHg. Postoperatively, among eyes without later cataract surgery, mean medicated IOP at all visits through 48 months was ≤ 13.7 mmHg (≥ 37% reduction), and annual unmedicated IOP was ≤ 18.4 mmHg (reductions of ≥ 30% vs. preoperative unmedicated IOP and ≥ 16% vs. preoperative medicated IOP). At all postoperative visits among eyes without additional surgery or medication, ≥ 91% of eyes had ≥ 20% IOP reduction on one medication versus preoperative medicated IOP. At month 48, 97 and 98% of eyes achieved IOP ≤ 15 and ≤ 18 mmHg, respectively, on one medication. Six eyes required additional medication, no eyes required additional glaucoma surgery, and safety measurements were favorable throughout follow-up. CONCLUSION: IOP control was achieved safely with two trabecular micro-bypass stents, one suprachoroidal stent, and postoperative prostaglandin. This microinvasive, ab interno approach introduces a possible new treatment option for refractory disease. TRIAL REGISTRATION: NCT01456390. FUNDING: Glaukos Corporation.

Amblyseius swirskii: what made this predatory mite such a successful biocontrol agent?

The predatory mite Amblyseius swirskii quickly became one of the most successful biocontrol agents in protected cultivation after its introduction into the market in 2005 and is now released in more than 50 countries. There are several key factors contributing to this success: (1) it can control several major pests including the western flower thrips, Frankliniella occidentalis, the whiteflies Bemisia tabaci and Trialeurodes vaporariorum and the broad mite, Polyphagotarsonemus latus, simultaneously in vegetables and ornamental crops; (2) it can develop and reproduce feeding on non-prey food sources such as pollen, which allows populations of the predator to build up on plants before the pests are present and to persist in the crop during periods when prey is scarce or absent; and (3) it can be easily reared on factitious prey, which allows economic mass production. However, despite the fact that A. swirskii provides growers with a robust control method, external demands were initially a key factor in promoting the use of this predator, particularly in Spain. In 2006, when exports of fresh vegetables from Spain were stopped due to the presence of pesticide residues, growers were forced to look for alternatives to chemical control. This resulted in the massive adoption of biological control-based integrated pest management programmes based on the use of A. swirskii in sweet pepper. Biological control increased from 5 % in 2005, 1 year before A. swirskii was commercially released, to almost 100 % of a total 6,000 ha of protected sweet pepper in Spain within 3 years. Later, it was demonstrated that A. swirskii was equally effective in other crops and countries, resulting in extensive worldwide use of A. swirskii in greenhouses.

Prospective unmasked randomized evaluation of the iStent inject (®) versus two ocular hypotensive agents in patients with primary open-angle glaucoma.

PURPOSE: The purpose of this study was to compare outcomes of subjects with open-angle glaucoma (OAG) not controlled on one medication who underwent either implantation of two iStent inject (®) trabecular micro-bypass devices or received medical therapy consisting of a fixed combination of latanoprost/timolol. PATIENTS AND METHODS: Of 192 subjects who qualified for the study and were enrolled, 94 were randomized to surgery with implantation of two iStent inject(®) devices in the treated eye and 98 to receive medical therapy. RESULTS: At the month 12 visit, 94.7% of eyes (89/94) in the stent group reported an unmedicated intraocular pressure (IOP) reduction of ≥20% versus baseline unmedicated IOP, and 91.8% of eyes (88/98) in the medical therapy group reported an IOP reduction ≥20% versus baseline unmedicated IOP. A 17.5% between-group treatment difference in favor of the iStent inject group was statistically significant (P=0.02) at the ≥50% level of IOP reduction. An IOP ≤18 mmHg was reported in 92.6% of eyes (87/94) in the iStent inject group and 89.8% of eyes (88/98) in the medical therapy group. Mean (standard deviation) IOP decreases from screening of 8.1 (2.6) mmHg and 7.3 (2.2) mmHg were reported in the iStent inject and medical therapy groups, respectively. A high safety profile was also noted in this study in both the iStent inject and medical therapy groups, as measured by stable best corrected visual acuity, cup-to-disc ratio, and adverse events. CONCLUSION: These data show that the use of iStent inject is at least as effective as two medications, with the clinical benefit of reducing medication burden and assuring continuous treatment with full compliance to implant therapy as well as having a highly favorable safety profile.

T-cell profiling and the immunodiagnosis of latent tuberculosis infection in patients with inflammatory bowel disease.

BACKGROUND: Factors associated with performance of interferon-γ release assays (IGRA) and the tuberculin skin test (TST) in screening for latent tuberculosis infection in patients with inflammatory bowel diseases (IBD) are still poorly understood. The influence of peripheral T-cell subset counts on the results also remain unclear. METHODS: Prospective single-center study in 205 patients with IBD. Latent tuberculosis infection screening included a chest radiograph, TST (retest if negative), and 2 IGRAs: QuantiFERON-TB Gold In-Tube (QFT-GIT) and TSPOT-TB (TSPOT). T-cell subpopulations were determined by flow cytometry. RESULTS: Twenty-one (10.2%) patients had an abnormal chest radiograph, 55 (26.8%) had a positive TST, 16 (7.8%) had a positive QFT-GIT, and 25 (12.6%) had a positive TSPOT. TST positivity was lower in patients on ≥2 immunosuppressants compared with the controls (5-aminosalicylic acid treatment) (10.4% versus 38.2%, respectively) (P = 0.0057). No other drugs influenced TST or IGRA positivity. In patients on corticosteroid treatment, anti-TNF treatment, or ≥2 immunosuppressants, IGRAs detected 10 cases of latent tuberculosis infection not identified by TST. TSPOT and QFT-GIT increased yield by 56% and 22%, respectively. No significant differences in T-cell subpopulations were found between patients with positive or negative TST or TSPOT results. However, patients with positive QFT-GIT findings had more CD8 T cells (mean, 883 ± 576 versus 484 ± 385 cells per microliter in patients with negative results) (P = 0.022). CONCLUSIONS: IGRAs can improve TST-based screening in patients with IBD on immunosuppressive therapy. A low CD8 count can affect QFT-GIT results. We suggest combining TSPOT and TST screening in patients with IBD on immunosuppressants.

Prospective, unmasked evaluation of the iStent® inject system for open-angle glaucoma: synergy trial.

INTRODUCTION: Micro-invasive glaucoma surgical implantation of trabecular micro-bypass stents, previously shown to be safe and effective for open-angle glaucoma (OAG) subjects during cataract surgery, was considered for evaluation as a sole procedure. The aim of this study was to evaluate the safety and intraocular pressure (IOP)-lowering efficacy after ab interno implantation of two Glaukos Trabecular Micro-Bypass iStent inject second generation devices in subjects with OAG. This study was performed at sites in France, Germany, Italy, Republic of Armenia, and Spain. METHODS: In this pan-European, multi-center prospective, post-market, unmasked study, 99 patients with OAG on at least two topical ocular hypotensive medications who required additional IOP lowering to control glaucoma disease underwent implantation of two GTS400 stents in a stand-alone procedure. Patients were qualified if they presented with preoperative mean IOP between 22 and 38 mmHg after medication washout. Postoperatively, subjects were assessed at Day 1, Months 1, 3, 6, 7, 9, and 12. IOP, medication use and safety were assessed at each visit. RESULTS: Sixty-six percent of subjects achieved IOP ≤18 mmHg at 12 months without medication, and 81% of subjects achieved Month 12 IOP ≤ 18 mmHg with either a single medication or no medication. Mean baseline washout IOP values decreased by 10.2 mmHg or 39.7% from 26.3 (SD 3.5) mmHg to 15.7 (SD 3.7) mmHg at Month 12. Mean IOP at 12 months was 14.7 (SD 3.1) mmHg in subjects not using ocular hypotensive medications. Reduction from preoperative medication burden was achieved in 86.9% of patients, including 15.2% with reduction of one medication and 71.7% with reduction of two or more medications. Postoperative complications occurred at a low rate and resolved without persistent effects. CONCLUSION: In this series, implantation of two trabecular micro-bypass second generation stents in subjects with OAG resulted in IOP and medication reduction and favorable safety outcomes.

Specific IgA and metalloproteinase activity in bronchial secretions from stable chronic obstructive pulmonary disease patients colonized by Haemophilus influenzae.

BACKGROUND: Haemophilus influenzae is the most common colonizing bacteria of the bronchial tree in chronic obstructive pulmonary disease (COPD), and positive cultures for this potentially pathogenic microorganism (PPM) has been associated with local inflammation changes that may influence the relationships between H. influenzae and the bronchial mucosa. METHODS: A cross-sectional analysis of stable COPD patients enrolled in the Phenotype and Course of Chronic Obstructive Pulmonary Disease (PAC-COPD) Study, focusing on bronchial colonization by H. influenzae, was performed. Specific IgA against the PPM was measured by optical density, and metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) using ELISA in sputum samples. Levels in patients colonized by H. influenzae and non-colonized patients were compared. RESULTS: Sputum supernatant for the measurement of specific IgA against H. influenzae was available from 54 stable COPD patients, who showed levels of specific IgA significantly lower in colonized (n=21) than in non-colonized patients (n=33) (15 [4-37] versus 31 [10-75], p=0.033, Mann-Whitney U test). Proenzyme MMP-9 was measured in 44 patients, and it was higher in colonized (n=12, 1903 [1488-6699] ng/ml) than in non-colonized patients (n=32, 639 [373-972] ng/ml) (p<0.001, Mann-Whitney U test). Active form of MMP-9 was also higher in colonized (126 [25-277] ng/ml) than in non-colonized patients (39 [14-68] ng/ml) (p=0.021, Mann-Whitney U test), and the molar ratio between proenzyme MMP-9 and TIMP-1 was above 1 (2.1 [0.1-12.5]) in colonized patients, significantly higher than the ratio found in non-colonized patients (0.2 [0.08-0.5]) (p=0.030, Mann-Whitney U test). CONCLUSIONS: Clinically stable COPD patients colonized by H. influenzae had lower levels of specific IgA against the microorganism and higher values of the active form of MMP-9 in their sputum supernatant than non-colonized patients. Bronchial colonization by H. influenzae may cause structural changes in the extracellular matrix through a defective defense and the production of active metalloproteinases.

Effect of bronchial colonisation on airway and systemic inflammation in stable COPD.

The recovery of potentially pathogenic microorganisms (PPMs) from bronchial secretions is associated with a local inflammatory response in COPD patients. The objective of this study was to determine the relationships between bronchial colonisation and both bronchial and systemic inflammation in stable COPD. In COPD patients recruited on first admission for an exacerbation, bacterial sputum cultures, interleukin (IL)-1ß, IL-6 and IL-8 levels, and blood C-reactive protein (CRP) were measured in stable condition. Bronchial colonisation was found in 39 of the 133 (29%) patients and was significantly related to higher sputum IL-1ß (median [percentile 25-75]; 462 [121-993] vs. 154 [41-477] pg/ml, p = 0.002), IL-6 (147 [71-424] vs. 109 [50-197] pg/ml, p = 0.047) and IL-8 values (15 [9-19] vs. 8 [3-15] (×10³) pg/ml, p = 0.002). Patients with positive cultures also showed significantly elevated levels of serum CRP (6.5 [2.5-8.5] vs. 3.5 [1.7-5.4] mg/l, p = 0.016). Bronchial colonisation by Haemophilus influenzae was associated with higher levels of IL-1ß and IL-8 and clinically significant worse scores on the activity and impact domains of the St. George's Respiratory Questionnaire. In conclusion, bronchial colonisation is associated with bronchial inflammation and high blood CRP levels in stable COPD patients, being Haemophilus influenzae related to a more severe inflammatory response and impairment in health-related quality of life.

Extended cervical mediastinoscopy: mature results of a clinical protocol for staging bronchogenic carcinoma of the left lung.

OBJECTIVE: The objective of this study is to evaluate the accuracy of extended cervical mediastinoscopy (ECM) in the staging of bronchogenic carcinoma (BC) of the left lung based on our updated experience. METHODS: From 1998 to 2003, 89 patients underwent routine ECM for staging of BC of the left lung. In 2004, routine positron emission tomography (PET) was included in our staging protocol and ECM was reserved for those with positive mediastinal or hilar PET images, large lymph nodes on computed tomography (CT) scan or central tumours. Following this protocol, from 2004 to 2010, we performed 132 selective ECM. ECM was considered positive when metastatic nodes or tumour involvement directly in the subaortic or para-aortic regions was confirmed pathologically. Patients with negative ECM underwent subsequent thoracotomy for tumour resection and systematic nodal dissection (SND). RESULTS: Two hundred and twenty-one ECMs were performed from 1998 to 2010 (89 routine and 132 selective). In the routine ECM protocol, four cases were positive and thoracotomy was contraindicated. The remaining 85 patients were operated and five had nodal disease in subaortic (LN5) or para-aortic (LN6) stations. In the selective ECM protocol (n = 188), 132 patients underwent ECM and in 19 it was positive; the remaining 113 patients underwent thoracotomy and SND found involved LN5 or LN6 in six patients; the other 56 patients underwent direct thoracotomy and four had positive LN5 or LN6. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of ECM were 0.67, 1, 1, 0.94 and 0.95, respectively. The staging values of routine/selective ECM protocols were 0.44/0.65, 1/1, 1/1, 0.94/0.94 and 0.94/0.95, respectively. CONCLUSIONS: Selective ECM protocol according to CT and PET findings has high negative predictive value and accuracy. Therefore, its selective use is recommended because it saves around 30% ECM without decreasing staging values of the current protocol.