Clinical and functional characteristics of individuals with alpha-1 antitrypsin deficiency: EARCO international registry.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history. METHODS: The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels < 11 µM and/or proteinase inhibitor genotypes PI*ZZ, PI*SZ and compound heterozygotes or homozygotes of other rare deficient variants. We describe the characteristics of the individuals included from February 2020 to May 2022. RESULTS: A total of 1044 individuals from 15 countries were analysed. The most frequent genotype was PI*ZZ (60.2%), followed by PI*SZ (29.2%). Among PI*ZZ patients, emphysema was the most frequent lung disease (57.2%) followed by COPD (57.2%) and bronchiectasis (22%). Up to 76.4% had concordant values of FEV1(%) and KCO(%). Those with impairment in FEV1(%) alone had more frequently bronchiectasis and asthma and those with impairment in KCO(%) alone had more frequent emphysema and liver disease. Multivariate analysis showed that advanced age, male sex, exacerbations, increased blood platelets and neutrophils, augmentation and lower AAT serum levels were associated with worse FEV1(%). CONCLUSIONS: EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function. Trial registration www. CLINICALTRIALS: gov (ID: NCT04180319).

Treatment of impacted or retained second molars with the miniscrew-supported pole technique: a prospective follow-up study.

BACKGROUND: Eruption disturbances of permanent molars are uncommon; however, it is important to treat them as soon as they are diagnosed. The main objective was to analyze the effectiveness of the "miniscrew-supported pole technique," a surgically assisted orthodontic procedure to force the eruption of impacted/retained second molars (M2s) when there are indicators of complex molar inclusion. An observational prospective study was carried out during a 2-year period. Sociodemographic, clinical and low-dose scanner variables were taken at baseline (T0). Follow-up variables (T1) were the time between surgery and tooth eruption, radiographic measurements, debonding of buttons, failure rate of miniscrews and success rate of eruption. RESULTS: A total of 21 patients (mean age of 13.9 years) with 24 retained/impacted M2s were recruited; 13 molars were maxillary (54.2%) and 11 (45.8%) were mandibular. Six (25%) were impacted molars and 18 (75%) primarily retained. At T0, molar angulation was mesial in six molars (25%), distal in five molars (20.8%) and 13 molars were vertically positioned (54.2%). Infraocclusion degree was moderate in four (16.7%) molars and severe in 20 (83.3%). Only three (12.5%) third molars were removed due to lack of space. All M2s managed to erupt, achieving a success rate of 100%; however, two molars of the same patient did not achieve occlusion. The period of eruption after surgery was 126.8 (117.3) days. Anatomical radicular alteration was the only variable independently related to a longer time of treatment (p = 0.027). CONCLUSIONS: The pole technique, using one mesial miniscrew and simple orthodontic mechanics, applies forces that succeed in erupting complicated retained/impacted M2s in a short period of time and with a low failure rate.

Contemporary outcomes of bladder carcinoma in situ treated with an adequate bacille Calmette-Guérin immunotherapy.

OBJECTIVE: To assess whether bacillus Calmette-Guérin (BCG) responsiveness after initiation of an adequate BCG treatment (at least five of six instillations of induction and at least two of three instillations of maintenance) impacts oncological outcomes in patients with carcinoma in situ (CIS) of the bladder treated with BCG immunotherapy. PATIENTS AND METHODS: Data were available for 193 patients with bladder CIS with or without associated cTa/cT1 disease who received an adequate BCG treatment between 2008 and 2015. Bladder biopsies were taken at 6 months and patients were then stratified as either BCG responsive (negative biopsies) or BCG unresponsive (positive biopsies). Inverse probability weighting (IPW)-adjusted Kaplan-Meier and IPW-adjusted Cox regression were performed to compare progression-free survival (PFS), radical cystectomy-free survival (RCFS), overall survival OS, and cancer-specific survival (CSS) in the two groups. RESULTS AND LIMITATIONS: Comparing the BCG-responsive and BCG-unresponsive groups, IPW-adjusted Kaplan-Meier analysis revealed, respectively, a median (interquartile range) of PFS of 9 (5-15) vs 48.5 (28-77) months (P = 0.001), a RCFS of 11 (9-15) vs 49 (24-76) months (P < 0.001), and a CSS of 25 (13-60) vs 109 (78-307) months (P = 0.004). On IPW-adjusted Cox regression analysis, BCG-unresponsive patients had a worse PFS (hazard ratio [HR] 3.40, 95% confidence interval [CI] 1.59-7.27), RCFS (HR 3.52, 95% CI 1.77-7), and CSS (HR 4.42, 95% CI 1.95-10.01). We found no significant differences for OS. CONCLUSION: Using an IPW method we found that lack of response after initiation of an adequate BCG treatment has prognostic implications beyond identification of complete response in patients with CIS. BCG-unresponsive patients, satisfying the novel definition of BCG unresponsive, showed a poor PFS, RCFS, and CSS. In this setting, the patients should be counselled regarding RC as a first option or enrolled in a clinical trial if they refuse RC or are unfit for surgery.

Evolution and Comparative Analysis of Hospitalizations in Spain Due to COPD and Bronchiectasis between 2004 and 2015.

Chronic obstructive pulmonary disease (COPD) is the leading cause of hospitalization for chronic respiratory illness in Spain. In recent years hospital admissions due to bronchiectasis have been increasing, although it is not known whether this is in proportion to COPD hospitalizations. Our main objective was to analyze the temporal evolution of discharges due to COPD, bronchiectasis, and their combination, and secondly, to assess their impact on in-hospital mortality and healthcare costs. We performed a retrospective study, based on the analysis of the Minimum Basic Data Set (MBDS) of hospital discharges using data from Spanish Ministry of Health with diagnostic codes of COPD or bronchiectasis between 2004 and 2015. We found 3 356 186 discharges with a diagnosis of COPD or bronchiectasis. After exclusions, 1 386 430 episodes were analyzed: 85.2% with COPD, 8.4% bronchiectasis, and 6.4% with both pathologies. Mean age of patients was 74.8 (10.9) years and with a male predominance of 80.1%. The increase in the annual number of discharges was greater in the two groups with bronchiectasis: 48.8% in the bronchiectasis group and 55.4% in the mixed group, compared to 6.6% in the COPD group. The mean length of stay was greater in both groups with bronchiectasis (p < 0.001), while in-hospital mortality was higher in the COPD group (p < 0.001). Similarly, the annual increase of costs was more evident in the two groups with bronchiectasis. Conclusions: Hospitalizations and health costs for bronchiectasis have increased in recent years significantly more than for COPD.Supplemental data for this aricle can be accessed here.

Pilot Trial of Extended Hypothermic Lung Preservation to Analyze Ischemia-reperfusion Injury in Pigs.

BACKGROUND: In lung transplantation (LT), the length of ischemia time is controversial as it was arbitrarily stablished. We ought to explore the impact of extended cold-ischemia time (CIT) on ischemia-reperfusion injury in an experimental model. METHODS: Experimental, randomized pilot trial of parallel groups and final blind analysis using a swine model of LT. Donor animals (n=8) were submitted to organ procurement. Lungs were subjected to 6h (n=4) or 12h (n=4) aerobic hypothermic preservation. The left lung was transplanted and re-perfused for 4h. Lung biopsies were obtained at (i) the beginning of CIT, (ii) the end of CIT, (iii) 30min after reperfusion, and (iv) 4h after reperfusion. Lung-grafts were histologically assessed by microscopic lung injury score and wet-to-dry ratio. Inflammatory response was measured by determination of inflammatory cytokines. Caspase-3 activity was determined as apoptosis marker. RESULTS: We observed no differences on lung injury score or wet-to-dry ratio any given time between lungs subjected to 6h-CIT or 12h-CIT. IL-1ß and IL6 showed an upward trend during reperfusion in both groups. TNF-α was peaked within 30min of reperfusion. IFN-γ was hardly detected. Caspase-3 immunoexpression was graded semiquantitatively by the percentage of stained cells. Twenty percent of apoptotic cells were observed 30min after reperfusion. CONCLUSIONS: We observed that 6 and 12h of CIT were equivalent in terms of microscopic lung injury, inflammatory profile and apoptosis in a LT swine model. The extent of lung injury measured by microscopic lung injury score, proinflammatory cytokines and caspase-3 determination was mild.

Adalimumab in Elderly Patients with Non-Infectious Uveitis. Safety and Efficacy.

Purpose: To assess the efficacy and safety of adalimumab in elderly patients with noninfectious uveitis (NIU).Methods: An observational, retrospective, multicenter study was done. Changes in best-corrected visual acuity (BCVA), inflammatory activity parameters, central retinal thickness (CRT), and the occurrence of adverse events (AE) developed during follow-up were recorded.Results: A total of 82 eyes from 41 patients 60 years of age and older with noninfectious uveitis treated with adalimumab were included. A significant improvement in BCVA (71.5 to 75.4 letters, p = .001) and in CRT (311.1 µm to 265 µm, p = .001) was observed. Moreover, a significant decrease from baseline in the rate of patients with anterior chamber cell (ACC) >0+ (34.6% to 5.7%, p = <0.001) or vitreous haze>0+ (21.3% to 4.3%, p = .002) was determined. AEs were observed in 11 patients (26.8%).Conclusion: Adalimumab can be safe and efficacious for the treatment of NIU in patients 60 years of age and older.

Outcomes of a Series of Patients with Post-Prostatectomy Incontinence Treated with an Adjustable Transobturator Male System or Artificial Urinary Sphincter.

INTRODUCTION: A prospective evaluation of outcomes in a series of patients with post-prostatectomy incontinence (PPI) treated with two different devices is presented. METHODS: Consecutive patients with PPI underwent interventions with an adjustable transobturator male system (ATOMS) or artificial urinary sphincter (AUS). Decisions were based on patient preference after physician counselling. Patient characteristics and operative and postoperative parameters including dryness, satisfaction, complications, revision and device durability were evaluated. RESULTS: One hundred twenty-nine patients were included: 102 (79.1%) received ATOMS and 27 (20.9%) AUS. Mean follow-up was 34.9 ± 15.9 months. No difference was observed between patient age (p = 0.56), ASA score (p = 0.13), Charlson index (p = 0.57) and radiation (p = 0.3). BMI was higher for AUS (27.1 vs. 29.7; p = 0.003) and also baseline incontinence severity (7.9% mild, 44.1% moderate and 48% severe for ATOMS vs. 11.1% moderate and 88.9% severe for AUS; p = 0.0007). Differential pad test was higher for AUS (- 470 vs. - 1000 ml; p < 0.0001) and so was ICIQ-SF (15.62 vs. 18.3; p < 0.001), but total dryness (76.5 vs. 66.7%; p = 0.33), social continence (90.2 vs. 85.2%; p = 0.49) and satisfaction (92.2 vs. 88.9%; p = 0.69) were equivalent. The postoperative complication rate was similar (22.6 vs. 29.6%; p = 0.4). The surgical revision rate was higher for AUS (6.9 vs. 22.2%; p = 0.029) and also the explant rate but did not reach statistical significance (4.9 vs. 14.8%; p = 0.09). Time to explant was shorter for AUS (log-rank p = 0.021). Regression analysis revealed radiation (p = 0.003) and incontinence severity (p = 0.029) predict total dryness, while complications (p < 0.005) and type of device (p = 0.039) independently predict surgical revision. CONCLUSIONS: Both ATOMS and AUS are effective devices. Pad test change for AUS exceeds that of ATOMS. The revision rate is higher for AUS, and durability is superior for ATOMS. The satisfaction rate is equivalent. Larger series and longer follow-up are needed to compare both devices more appropriately. According to our experience, the AUS is not the only gold standard for PPI.

Uveitic macular edema response to intravitreal dexamethasone implant is independent of optical coherence tomography findings.

PURPOSE: To identify predictive response optical coherence tomography (OCT) findings in uveitic macular edema (UME) treated with intravitreal dexamethasone implant (DEX). METHODS: Retrospective study of 66 eyes (53 patients) treated with DEX for UME. SD-OCT macular scans were collected prior to DEX treatment and 6 weeks and 3 months after the DEX implant. OCT images were evaluated for qualitative and quantitative characteristics (central retinal thickness, CRT and macular volume, MV). A multivariate analysis of covariance (ANCOVA) was carried out to study the predictive influence of OCT and clinical covariates on outcomes. The main outcome was a composite endpoint based on the simultaneous gain of 5 or more letters associated with a 20% or more reduction in CRT. RESULTS: A significant improvement in BCVA at 6 weeks (mean change from baseline -0.2, SD 0.3) and 3 months (mean -0.2, SD 0.4) was observed after the DEX implant. A significant decrease in CRT (change from baseline -187.7 µm at 3 months) and MV (change from baseline -1.7 mm3 at 3 months) were also observed. An association of ≥ 5-letter improvement in BCVA and a ≥ 20% CRT reduction was observed in 44.6% of cases at 6 weeks and 31.4% at 3 months. ANCOVA multivariate analyses found CRT at 3 months independent from baseline clinical variables but from CRT. CONCLUSION: DEX implant is an effective treatment for UME independently of basal characteristics, producing both a gain of visual acuity and improvement of macular anatomy by OCT measures at 3 months.

Systemic Regulatory T Cells and IL-6 as Prognostic Factors for Anatomical Improvement of Uveitic Macular Edema.

Purpose: To investigate whether systemic immune mediators and circulating regulatory T cells (Tregs) could be prognostic factors for anatomic outcomes in macular edema secondary to non-infectious uveitis (UME). Methods: Multicenter, prospective, observational, 12-month follow-up study of 60 patients with UME. Macular edema was defined as central subfield thickness (CST) > 300 µm measured with spectral domain optical coherence tomography (SD-OCT). Serum samples and peripheral blood mononuclear cells (PBMC) were obtained from venous blood extraction at baseline. Serum levels of IL-1ß, IL-6, IL-8, IL-17, MCP-1, TNF-α, IL-10, and VEGF were determined by Luminex. Tregs population, defined as CD3+CD4+FoxP3+ in PBMC, was determined by flow cytometry. Main outcome measure was the predictive association between searched mediators and CST sustained improvement, defined as CST < 300 microns or a 20% CST decrease, at 6 months maintained until 12-months compared to baseline levels. Results: Multivariate logistic regression analysis showed an association between CST sustained improvement at 12 months follow-up and IL-6 and Tregs baseline levels. Higher IL-6 levels were associated with less events of UME improvement (OR: 0.67, 95% CI (0.45-1.00), P = 0.042), whereas higher levels of Tregs favored such improvement (OR: 1.25, 95% CI: 1.12-2.56, P = 0.049). Conclusions: Increased levels of Tregs and reduced levels of IL-6 in serum may be prognostic factors of sustained anatomical improvement in UME. These findings could enforce the opportunity to develop more efficient and personalized therapeutic approaches to improve long-term visual prognosis in patients with UME.

Analysis of Blood Biomarkers in Patients with Chronic Obstructive Pulmonary Disease (COPD) and with Asthma-COPD Overlap (ACO).

Chronic obstructive pulmonary disease (COPD) is a heterogeneous entity with different clinical phenotypes, such as asthma-COPD overlap (ACO). The aim of this retrospective study was to compare routine blood biomarkers in patients with ACO and the remaning COPD phenotypes. Data were collected from stable COPD patients visited in during 2018, including C-reactive protein (CRP), fibrinogen, neutrophyl/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR).A total of 77 patients with COPD were included, 24 (31%) fulfilled the diagnosis of ACO. Clinically, patients with ACO presented more dyspnoea and wheezing. Regarding laboratory parameters, both groups had low levels of lymphocytes, especially the non-ACO group (24.2% vs. 29.3%; p = 0.031), patients with ACO had significantly higher eosinophil counts (4.7% vs. 1.9%; p < 0.001) but a lower percentage of neutrophils (56.8% vs. 64.7%; p = 0.003), NLR and PLR (2.5 vs. 3.8; p = 0.013 and 115 vs. 160; p = 0.063, respectively). In conclusion, besides the expected eosinophilic inflammation in patients with ACO, both groups had low levels of lymphocytes, especially the non-ACO group. The low levels of lymphocytes, in particular in non-ACO patients, should be confirmed in larger studies.

Drug Retention Rate and Causes of Discontinuation of Adalimumab in Uveitis: Real-World Data from the Biotherapies in Uveitis (BioÚvea) Study Group.

PURPOSE: To study the drug retention rate (DRR), causes, and predictors of discontinuation of adalimumab (ADA) in a real-world uveitis setting. DESIGN: Multicentric, nationwide, registry-based, ambispective, observational study. PARTICIPANTS: Patients treated with ADA for noninfectious uveitis (NIU) in the Biotherapies for Uveitis (BioÚvea) Spanish registry from November 2016 to November 2017. METHODS: Demographics, clinical data, timing, and reasons for discontinuation, if occurred, were recorded. The DRR and drug retention time (DRT) were estimated using the Kaplan-Meier method. Median follow-up was analyzed by reverse Kaplan-Meier. Log-rank test was used for comparisons. Cox proportional-hazards model (PHM) and propensity score matching were used to identify predictors for discontinuation due to inefficacy and adverse events. MAIN OUTCOME MEASURES: Drug retention rate and DRT. RESULTS: A total of 392 patients were analyzed, including 218 women. Median age was 39 (interquartile range, 25) years. Nonanterior uveitis was recorded in 242 patients. Median follow-up was 49.07 (0.97-131.67) months, median DRT (survival) was 69.3 months, and 14 patients were lost to follow-up. The DRR at 6, 12, 24, and 60 months was 92.97%, 87.68%, 76.31%, and 54.28%, respectively. Adalimumab was discontinued in 151 patients. Discontinuation was due to lack or loss of efficacy in 74 patients, adverse event in 34 patients, and sustained quiescence in 25 patients. Recorded adverse events included infections in 10 patients and malignant neoplasms in 3 patients. Concurrent classic immunomodulatory therapy (IMT) was given to 251 patients. We did not find DRT differences regarding the use of concurrent IMT. Adalimumab was prescribed as a second or greater biotherapy line in 76 patients who showed shorter DRT (P = 0.038). Starting ADA in nonbiotherapy-naive patients was a predictor for "discontinuation due to inefficacy," whereas undifferentiated uveitis was a predictor for "discontinuation due to adverse event." Drug retention time was significantly shorter when spared or intensified, mainly due to discontinuation after sustained quiescence. CONCLUSIONS: Drug retention rate of ADA in uveitis at 60 months was 54.28%, with a good safety profile. The use of concurrent IMT did not show a significant influence on DRT. The use of ADA as a second or further biotherapy could be predictive for discontinuation due to inefficacy. Undifferentiated uveitis may be prone to premature discontinuation of ADA due to adverse events.

The coexpression of fibroblast activation protein (FAP) and basal-type markers (CK 5/6 and CD44) predicts prognosis in high-grade invasive urothelial carcinoma of the bladder.

High-grade urothelial carcinoma (UC) of the bladder is a heterogeneous disease with dismal prognosis. Bladder tumors with basal phenotype are intrinsically aggressive, and morphological parameters that define disease staging remain main prognosticators. We intend to evaluate the role of cancer-associated fibroblasts (CAFs) in the prognosis of bladder cancer and its association with basal and luminal phenotypes. Clinical and pathological parameters, including the immunohistochemical expression of fibroblast activation protein (FAP) and markers of basal (CK5/6, CD44) and luminal (CK20, GATA3) phenotypes, have been investigated in a series of 121 patients with UC of the bladder treated by radical cystectomy with lymph node dissection, and their implication in long-term cancer-specific survival has been evaluated. A cytoplasmic immunostaining of FAP in CAFs implies worse disease-specific survival (hazard ratio [HR] = 1.68; P = .048). FAP expression is associated with tumor staging (P < .0001), with best discrimination at T2a/T2b level, and with negative expression of markers of luminal phenotype, such as CK20 (P < .0001) and GATA3 (P = .005). In the multivariate analysis, simultaneous expression of FAP, CK5/6, and CD44 is a strong prognosticator of disease-specific survival (HR = 2.3; P = .001), together with nodal invasion (HR = 3.47; P < .0001) and bladder infiltration up to deep muscle or beyond (HR = 2.47; P = .02). There is no association between positive FAP expression in primary tumor and nodal disease (P = .22). FAP expression in CAFs favors tumor invasion in high-grade invasive UC of the bladder with basal phenotype. This new immunohistochemical marker could be added to the routine immunohistochemical protocol to predict clinical behavior in these patients.

Anatomic Response to Intravitreal Dexamethasone Implant and Baseline Aqueous Humor Cytokine Levels in Diabetic Macular Edema.

Purpose: To determine whether baseline cytokine aqueous humor (AH) levels are associated with diabetic macular edema (DME) anatomic response to dexamethasone intravitreal implant (DEX) injection. Methods: This was a prospective cohort study of DME cases receiving DEX treatment. Seventy patients were recruited with center-involving DME with spectral-domain (SD) optical coherence tomography (OCT) detection of central macular thickness (CMT) ≥300 µm on macular cube 518 × 128-µm scan protocol (Cirrus SD-OCT). DEX injection and anterior chamber tap to obtain an AH sample were performed at the same time. Multiplex immunoassay was carried out for interleukin (IL)-1ß, IL-3, IL-6, IL-8, IL-10; monocyte chemoattractant protein (MCP)-1; interferon gamma-induced protein (IP)-10; tumor necrosis factor (TNF)-α; and vascular endothelial growth factor (VEGF). A follow-up visit and OCT exam were undertaken 6 to 8 weeks afterward. The association between AH cytokine baseline levels and change in CMT and macular volume (MV) was defined as main outcome measure. Results: Multivariate linear regression analysis showed a higher decrease in MV to be associated (Rs of 0.512) with four baseline items: higher MCP-1 (ß = -0.4; P = 0.028), higher CMT (ß = -0.003; P = 0.024), decreased visual acuity (ß = -0.7; P = 0.040), and a diffuse retinal thickening (DRT) OCT pattern (ß = -1.3; P < 0.001). Logistic regression found DRT also to be associated with higher odds of a good MV response (odds ratio, 31.96; 95% confidence interval [CI] 7.11-143.72; P < 0.001). Conclusions: Even though visual acuity response and anatomic effect are not always correlated in DME, we found that baseline elevated MCP-1 AH levels and DRT pattern were biomarkers that predicted a future favorable anatomic response to DEX.

Practical Guide to the Identification and Diagnosis of Asthma-COPD Overlap (ACO).

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality around the world. COPD is characterised by a heterogeneous clinical presentation and prognosis which may vary according to the clinical phenotype. One of the phenotypes of COPD most frequently studied is the asthma-COPD overlap (ACO), however, there are no universally accepted diagnostic criteria for ACO. It is recognised that the term ACO includes patients with clinical features of both asthma and COPD, such as more intense eosinophilic bronchial inflammation, more severe respiratory symptoms and more frequent exacerbations, but in contrast, it is associated with a better prognosis compared to COPD. More importantly, ACO patients show better response to inhaled corticosteroid treatment than other COPD phenotypes. The diagnosis of ACO can be difficult in clinical practice, and the identification of these patients can be a challenge for non-specialized physicians. We describe how to recognise and diagnose ACO based on a recently proposed Spanish algorithm and by the analysis of three clinical cases of patients with COPD. The diagnosis of ACO is based on the diagnosis of COPD (chronic airflow obstruction in an adult with significant smoking exposure), in addition to a current diagnosis of asthma and/or signficant eosinophilia.

Predictors for functional and anatomic outcomes in macular edema secondary to non-infectious uveitis.

AIMS: We aimed to investigate predictive factors for visual and anatomic outcomes in patients with macular edema secondary to non-infectious uveitis. MATERIAL AND METHODS: We conducted a multicenter, prospective, observational, 12-month follow-up study. Participants included in the study were adults with non-infectious uveitic macular edema (UME), defined as central subfoveal thickness (CST) of >300 µm as measured by spectral domain optical coherence tomography (SD-OCT) and fluid in the macula. Demographic, clinical and tomographic data was recorded at baseline, 1, 3, 6 and 12 months. Foveal-centered SD-OCT exploration was set as the gold-standard determination of UME using a standard Macular Cube 512x128 A-scan, within a 6 x 6 mm2 area, and the Enhanced High Definition Single-Line Raster. To assess favorable prognosis, the main outcomes analyzed were the best-corrected visual acuity (BCVA) and the CST. Favorable prognosis was defined as sustained improvement of BCVA (2 lines of gain of the Snellen scale) and CST (decrease of 20% of the initial value or <300 µm) within a 12 month period. RESULTS: Fifty-six eyes were analyzed. The number of eyes with sustained improvement in the CST was 48 (86.2%), against 23 (41.1%) eyes with sustained improvement in BCVA. Favorable prognosis, as defined above, was observed in 18 (32.1%) eyes. UME prognosis was negatively correlated with baseline foveal thickening, alteration in the vitreo-macular interface and cystoid macular edema. In contrast, bilaterally, systemic disease and the presence of anterior chamber cells were predictive of favorable prognosis. CONCLUSION: Available treatment modalities in UME may avoid chronic UME and improve anatomic outcome. However, the proportion of functional amelioration observed during 12 months of follow-up is lower. Thicker CST, alteration in the vitreo-macular interface and cystoid macular edema may denote less favorable prognosis. Conversely, bilaterally, systemic disease and anterior chamber cells may be associated with favorable prognosis in UME.

Effectiveness of Adjustable Transobturator Male System (ATOMS) to Treat Male Stress Incontinence: A Systematic Review and Meta-Analysis.

INTRODUCTION: Adjustable transobturator male system (ATOMS) is a surgical device developed to treat male stress urinary incontinence (SUI) after prostate surgery. The objective was to assess the effectiveness of the ATOMS device to treat male SUI as described in the literature. METHODS: Two independent reviewers identified studies eligible for a systematic review and meta-analysis of various sources written in English, German and Spanish, using the databases PubMed, EMBASE and Web of Science. We excluded studies on female incontinence. We employed the DerSimonian and Laird method for defining heterogeneity, calculating the grouped standard mean deviation (SMD). The primary objective of this review is the assessment of clinical efficacy based on the achievement of dryness after device adjustment, defined as use of no pad or one safety pad per day (PPD). The secondary objective was focused on analysing improvement of incontinence with the device. Magnitude of effect was calculated by analysing decrease in pad count (PPD) and/or in 24-h pad test. Number and severity of complications according to Clavien-Dindo classification were also reviewed. RESULTS: The pooled data of 1393 patients from 20 studies (13 retrospective and 7 prospective) showed that treatment with ATOMS resulted in a mean 67% dryness rate and 90% improvement after adjustment. Mean total number of system fillings per patient was 2.4. Mean pad count and 24-h pad test decrease were - 4.14 PPD and - 443 cc, respectively. There is significant heterogeneity of the sample analysed, mainly based on variable baseline severity of incontinence, proportion of patients treated with irradiation and different generation devices. Proportion of irradiated patients affected dryness rate (p = 0.0014), together with baseline severity of incontinence (p = 0.0035) and different generation device used (p < 0.0001). Standardized mean follow-up was 20.9 months, with complications occurring in 16.4% (major complications 3.0%) and explantations in 5.75%. No randomized study has been developed so far to compare ATOMS to other devices for treating male SUI. CONCLUSION: Despite the evidence being exclusively based on descriptive studies and limited follow-up, ATOMS has proven to be a safe alternative to treat different degrees of male SUI after prostate surgery. Better results are evidenced for patients with less than 6 PPD before implantation, non-irradiated patients and use of third-generation device with silicone-covered pre-attached scrotal port.

Adjustable Transobturator Male System after Failed Surgical Devices for Male Stress Urinary Incontinence: A Feasibility Study.

OBJECTIVES: Feasibility study to evaluate the efficacy and safety of Adjustable Transobturator Male System (ATOMS) after failed surgical devices for male stress urinary incontinence (SUI). MATERIALS AND METHODS: Thirty patients were implanted with ATOMS after they were implanted with surgical device/s previously. SUI severity was evaluated as dryness (0-1 pad/day), mild (2 pads/day), moderate (3-5 pads/day), or severe (≥6 pads/day). Change in pad-test and pad-count after adjustment, operative parameters, patient satisfaction, and number and grade of complications were investigated. RESULTS: Previous failed treatment methods were artificial urinary sphincter (AUS; n = 19), Advance (n = 10), and Virtue (n = 1). Six cases had multiple previous treatments. Preoperative SUI was mild 6 (20%), moderate 11 (36.7%), and severe 13 (43.3%). Median pad-test decreased from 435 mL baseline to 10 mL after adjustment and pad-count from 4 to 0. Dry-rate was 76.7 and 83.3% declared satisfied. Postoperative SUI distribution was mild in 3 (10%) and moderate in 4 (13.3%). No patient had urinary retention after catheter removal. Complications presented in 4 (13.3%; 3 grade-I, 1 grade-II). After a median of 24 months follow-up, no system experienced infection or urethral erosion and 1 (3.3%) was removed for inefficacy. CONCLUSION: Based on short-term efficacy and patient satisfaction, ATOMS can be a realistic alternative for male SUI after other failed systems, including AUS. The absence of urethral erosion and limited infective problems makes this alternative attractive for cases with previous failed treatments.

Urethroplasty After Urethral Urolume Stent: An International Multicenter Experience.

OBJECTIVE: To evaluate the outcomes and factors affecting success of urethroplasty in patients with stricture recurrence after Urolume urethral stent. MATERIAL AND METHODS: This is a retrospective international multicenter study on patients treated with urethral reconstruction after Urolume stent. Stricture and stent length, time between urethral stent insertion and urethroplasty, age, mode of stent retrieval, type of urethroplasty, complications and baseline, and posturethroplasty voiding parameters were analyzed. Successful outcome was defined as standard voiding, without need of any postoperative adjunctive procedure. RESULTS: Sixty-three patients were included. Stent was removed at urethroplasty in 61 patients. Reconstruction technique was excision and primary anastomosis in 14 (22.2%), dorsal onlay buccal mucosa graft (BMG) in 9 (14.3%), ventral onlay BMG in 6 (9.5%), dorsolateral onlay BMG in 9 (14.3%), ventral onlay plus dorsal inlay BMG in 3 (4.8%), augmented anastomosis in 5 (7.9%), pedicled flap urethroplasty in 6 (9.5%), 2-stage procedure in 4 (6.4%), and perineal urethrostomy in 7(11.1%). Success rate was 81% at a mean 59.7 ± 63.4 months. Dilatation or internal urethrotomy was performed in 10 (15.9%) and redo-urethroplasty in 5 (7.9%). Total International Prostate Symptom Score, quality of life, urine maximum flow, and postvoid residual significantly improved (P <.0001). Complications occurred in 8 (12.7%), all Clavien-Dindo ≤2. Disease-free survival rate after reconstruction was 88.1%, 79.5%, and 76.7% at 1, 3, and 5 years, respectively. Explant of individual strands followed by onlay BMG is the most common approach and was significantly advantageous over the other techniques (P = .018). CONCLUSION: Urethroplasty in patients with Urolume urethral stents is a viable option of reconstruction with a high success rate and very acceptable complication rate. Numerous techniques are viable; however, urethral preservation, tine-by-tine stent extraction, and use of BMG augmentation produced significantly better outcomes.

Long-term evolution of lung function in individuals with alpha-1 antitrypsin deficiency from the Spanish registry (REDAAT).

Background: The clinical course of alpha-1 antitrypsin deficiency (AATD) is very heterogeneous. It is estimated that 60% of individuals with severe AATD (Pi*ZZ) develop emphysema. The main objective of this study was to describe the outcomes of long-term lung function in individuals with AATD-associated emphysema after at least 8 years of follow-up. Materials and methods: We performed a retrospective analysis of longitudinal follow-up data of AATD PiZZ patients from the Spanish registry (AATD Spanish Registry [REDAAT]). The main follow-up outcome was the annual rate of decline in forced expiratory volume in 1 second (FEV1) calculated using the FEV1 values at baseline and in the last post-bronchodilator spirometry available. Results: One hundred and twenty-two AATD PiZZ patients were analyzed. The median follow-up was 11 years (interquartile range =9-14). The mean FEV1 decline was 28 mL/year (SD=54), with a median of 33 mL/year. Tobacco consumption (ß=19.8, p<0.001), previous pneumonia (ß=27.8, p=0.026) and higher baseline FEV1% (ß=0.798, p=0.016) were independently related to a faster FEV1 decline. Conclusion: In this large cohort with a long follow-up, we observed a very variable decline of FEV1. However, the mean FEV1 decline was similar to that observed in large cohorts of smoking-related COPD. Tobacco consumption, previous pneumonia and better lung function at baseline were related to a faster decline in FEV1. These results highlight the importance of early diagnosis and effective treatment.

Treatment of male stress urinary incontinence with the adjustable transobturator male system: Outcomes of a multi-center Iberian study.

AIM: To evaluate effectiveness and safety of the adjustable transobturator male system (ATOMS) for male stress urinary incontinence (SUI). MATERIAL AND METHODS: A retrospective multicenter study was conducted in nine Iberian institutions using a board-approved database for 215 patients intervened between 2012 and 2017, with no case excluded. Continence status, patient satisfaction, number, and grade of complications (Clavien-Dindo) and factors affecting dry rate at adjustment were evaluated. Multivariate analysis defined the population at best success rate. Incontinence recurrence due to device failure and/or explant was evaluated and Kaplan-Meier curve for durability performed. RESULTS: Adjustment was achieved at a mean 1.4 ± 1.9 fillings. Dry-rate after adjustment was 80.5% (96.2% mild and 75.3% moderate-severe), 121 (56.3%) used no pads, and 52 (24.2%) a security pad with urine loss under 10 mL. Mean basal daily pad-test and pad-count decreased from 484 ± 372.3 mL and 3.9 ± 2 pads to 63.5 ± 201.2 mL and 0.9 ± 1.5pads (both P < 0.0001). Satisfaction rate was 85.1% (94.3% mild and 82.1% moderate-severe). Factors associated to dryness were: lesser severity of SUI (P < .0001), absence of radiotherapy (P = 0.0002) and device generation (P = 0.05). Multivariate analysis revealed absence of radiation (OR = 3.12; 1.36-7.19), mild (OR = 19.61; 3.95-100), and moderate (OR = 2.48; 1.1-5.59) SUI were independent predictors. Complications presented in 33(15.35%); 66.7% grade 1, 9.1% grade 2, and 24.2% grade 3. At 24.3 ± 15 mo mean follow-up device was explanted in seven (3.25%) and SUI worsened after adjustment in nine (4.2%). Dry-rate at follow-up was 73% and durability of device in dry patients at adjustment was 89.8% (82.9-94) at 2-years. CONCLUSIONS: This study confirms ATOMS device is safe and achieves high treatment efficacy and patient satisfaction in a multicenter setting. Significantly better results are achieved in less severe and non-irradiated cases. Durability of the device is reassuring in the short-term.