The Effectiveness of Biological Agents on Chronic Rhinosinusitis with Nasal Polyposis in Patients with Comorbid Asthma: A Multicenter Real-Life Study from Türkiye.

Background and Objectives: Real-life data on the efficacy of biologic agents (BAs) on asthma-comorbid CRSwNP are needed. Our primary goal is to investigate the effects of BAs on CRSwNP symptoms, as well as endoscopic and tomography scores. Our secondary goal is to show a reduction in the frequency of acute sinusitis exacerbations and the need for surgery. Materials and Methods: We conducted a multicenter, retrospective, real-life study. We screened the patients with asthma-comorbid CRSwNP treated with omalizumab or mepolizumab. A total of 69 patients (40 F/29 M; omalizumab n = 55, mepolizumab n = 14) were enrolled. We compared the visual analog scale (VAS), sinonasal outcome test-22 (SNOT-22), nasal congestion score (NCS), Lund-Mackay computed tomography score (LMS), and total endoscopic polyp scores (TPS) before and after BAs. We evaluated the endoscopic sinus surgery (ESS) and acute exacerbations of chronic rhinosinusitis (AECRS) frequencies separately, according to the BAs. Results: The overall median (min-max) age was 43 (21-69) years. The median (min-max) of biologic therapy duration was 35 (4-113) months for omalizumab and 13.5 (6-32) for mepolizumab. Significant improvements were seen in VAS, SNOT-22, and NCS with omalizumab and mepolizumab. A significant decrease was observed in TPS with omalizumab [95% CI: 0-4] (p < 0.001), but not with mepolizumab [95% CI: -0.5-2] (p = 0.335). The frequency of ESS and AECRS were significantly reduced with omalizumab [95% CI: 2-3] (p < 0.001) and [95% CI: 2-5] (p < 0.001); and mepolizumab [95% CI: 0-2] (p = 0.002) and [95% CI: 2-8.5] (p < 0.001), respectively. There was no significant difference in LMS with either of the BAs. Conclusions: Omalizumab and mepolizumab can provide a significant improvement in the sinonasal symptom scores. BAs are promising agents for CRSwNP patients with frequent exacerbations and multiple surgeries.

Posterior segment parameters after uveitic cataract surgery: A prospective study with 1-year results.

PURPOSE: To evaluate the changes in posterior segment after uncomplicated cataract surgery in uveitic patients. METHODS: Retinal nerve fiber layer thickness (RNFLT), ganglion cell layer thickness (GCLT), central macular thickness (CMT), and choroidal thickness (CT) of 38 eyes of 28 patients were measured pre- and postoperatively on day 1, week 1, and month 1, 3, 6, 9, and 12. RESULTS: The RNFLT increased after surgery. Although the measurements taken were higher than the baseline CMT at all postoperative times, no significant difference was detected between the paired comparisons. The GCLT was found to be higher than the baseline value in all quadrants at the 12th month. A decrease in CT was observed at 5 measured points on the 1st day compared to the baseline. CONCLUSION: During the 1-year follow-up, the effect of cataract surgery on the retina and choroid in uveitic eyes was most evident at the postoperative month 1.

Complication and conversion outcomes in transoral endoscopic thyroidectomy vestibular approach (TOETVA): a retrospective multicenter propensity score-matched cohort study.

Transoral endoscopic thyroidectomy with vestibular approach (TOETVA) is a scarless thyroid surgery used as an alternative to open conventional surgery. Our aim was to investigate possible risk factors for complications and conversion during TOETVA. The study was conducted internationally by centres from Turkiye, the Republic of Korea, Italy, and Peru. A total of 406 patients who underwent TOETVA and were ≥ 18 years of age were included in the study. Demographic, pre-, intra-, and postoperative data were collected and compared between the groups with/without complication/conversion to identify possible predictors of complication/conversion. Subsequently, patients with complication/conversion were matched by the hospital, age, sex, and American Society of Anesthesiologists classification score using a propensity score (PSM) of 1:3 to eliminate confounding differences. Results were reported for the un-matched and matched groups. Complications occurred in 11 (2.7%) patients. High body mass index (26.4 ± 3.4 vs. 23.3 ± 3.7, p = 0.007), larger tumor size (1.7 ± 1.3 cm. vs. 1.1 ± 1.0 cm, p = 0.012), larger thyroid volume (20.0 ± 9.2 vs. 12.8 ± 8.5, p = 0.007) and long operation time (127.8 ± 45.0 min. vs. 97.7 ± 38.5 min., p = 0.008) were significantly associated with complications in un-matched analyses. Older age (42.7 ± 8.0 vs. 34.9 ± 9.2, p = 0.023), high BMI (26.7 ± 3.2 vs. 23.3 ± 3.7, p = 0.012), and longer operation time (160.1 ± 54.1 min. vs. 97.4 ± 37.8, p = 0.001) were significantly related to conversion in un-matched analyses. However, significance was lost after PSM for both complication and conversion. The data from this study conducted on TOETVA cases do not suggest a risk factor for complications and conversion with PSM.

High-flow nasal cannula oxygen in children with bronchiolitis: A randomized controlled trial.

OBJECTIVE: To determine whether high-flow nasal cannula oxygen (HFNCO) provided enhanced respiratory support in bronchiolitis than low-flow oxygen (LFO). METHODS: We conducted a prospective, randomized controlled trial in children between 1 and 24 months diagnosed with moderate-to-severe bronchiolitis requiring oxygen therapy. Participants received LFO via face mask (6-10 L/min) or HFNCO (2 L/kg/min). Primary outcomes were the time that heart rate (HR) and respiratory rate (RR) return to their normal range for age and the time that baseline clinical respiratory score (CRS) regress to a lower severity score. Secondary outcomes were changes in HR, RR, and CRS over time, length of stay (LOS), duration of oxygen requirement, treatment failure, and adverse event (AE). RESULTS: Eighty-seven children were enrolled (48 in LFO; 39 in HFNCO). The time that HR and RR baseline values reached their normal range for age was shorter in HFNCO therapy (2.0 h [1.0-4.0] vs. 12.0 h [2.0-24.0], and 4.0 h [2.0-12.0] vs. 24.0 h [4.0-48.0], respectively; p < 0.001); additionally, the improvement in CRS emerged more quickly in children treated with HFNCO (2.0 h [1.0-4.0] vs. 4.0 h [2.0-24.0]; p = 0.003). While the duration of oxygen requirement (19.0 h [4.0-30.0] vs. 29.5 h [14.0-45.7]; p = 0.009) and treatment failure (3% vs. 21%) was statistically lower in children who received HFNCO, there were no differences in LOS and AE between groups. CONCLUSION: HFNCO may provide enhanced respiratory support with a notable improvement in HR, RR, and CRS than LFO. Comprehensive studies are needed to assess the clinical efficacy of HFNCO therapy.

Investigation of possible associations of the BDNF, SNAP-25 and SYN III genes with the neurocognitive measures: BDNF and SNAP-25 genes might be involved in attention domain, SYN III gene in executive function.

OBJECTIVES: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous disorder and Sluggish Cognitive Tempo (SCT) might be a second inattention disorder that might be even affected by different attention pathways. SCT is characterized by daydreaming, mental confusion, staring blankly and hypoactivity. In the present study, we evaluated 5 common variants (rs6265, rs3746544, rs1051312, rs133946 and rs133945) located in 3 candidate genes (BDNF, SNAP25 and SYN III) that are known to take part in synaptic plasticity and neurotransmitter transmission. METHODS: We tested the effects of these variants on neuropsychological findings assessed by a computer-based neuropsychological test battery in children with inattention symptoms (SCT and/or ADHD). RESULTS: BDNF (rs6265), SNAP25 (rs3746544 and rs1051312) and SYN III (rs133946 and rs133945) polymorphisms were associated with variable cognitive measures. BDNF gene (rs6265) polymorphism Met allele carriers and SNAP25 gene (rs3746544) T allele carriers had an association with the attention domain. SNAP25 gene (rs1051312) C allele carriers were only associated with reaction time scores. Cognitive flexibility, which is one of the key components of executive function evaluation and shifting attention test scores were associated with BDNF (rs6265) Met allele and SYN III (rs133946) gene G allele. SYN III (rs133945) gene C allele carriers had an association with verbal memory correct hit scores. CONCLUSIONS: As a conclusion, BDNF, SNAP25 and SYN III genes were associated with specific neurocognitive outcomes in children with inattention symptoms. It is important to note that exploring genotyping effects on neurocognitive functions instead of a heterogeneous psychiatric diagnosis can improve our understanding of psychopathologies.

Anterior segment parameters after uveitic cataract surgery: A prospective study with 1-year results.

PURPOSE: To determine the changes in anterior segment parameters in uveitic patients undergoing uncomplicated cataract surgery. METHODS: The best corrected visual acuity (BCVA), intraocular pressure (IOP), central corneal thickness (CCT), anterior chamber angle (ACA), anterior chamber depth (ACD), and axial length (AXL) of the 38 eyes of 28 well-controlled uveitic patients who underwent cataract surgery were monitored for 12 months. RESULTS: Mean BCVA improved significantly at the postoperative visits when compared to the baseline (all P<0.001). Mean CCT increased on the first day compared to the preoperative value (627.62±71.16 vs. 572.18±53.52 µm, P=0.015) and then returned to the preoperative value at 3 months (572.27±49.93 µm). ACA showed a significant increase postoperatively in the first month (54.65±5.52 vs. 43.50±9.13°) and then decreased at 3 months (51.85±5.52°), remaining stable afterwards (51.73±6.59° at 12 months). ACD as measured by Sirius topography and IOLMaster 500 was higher at the follow-up times compared to the preoperative value (P<0.001). AXL at 1. month was significantly lower than the preoperative level (23.14±0.74 vs. 23.54±0.68 mm, P=0.003). CONCLUSION: Following successful cataract surgery in well-controlled uveitic eyes, the CCT showed a rapid increase on the first day and then decreased to the preoperative level at the third month. ACA increased in the postoperative first month and then decreased, but it was higher than the baseline at all postoperative visits. ACD increased in the postoperative first week.

May ganglion cell complex analysis be a marker for glaucoma susceptibility in unilateral Fuchs' uveitis syndrome?

PURPOSE: To compare retinal nerve fiber layer (RNFL) thickness and ganglion cell-inner plexiform layer thickness (GCIPLT) in the affected eyes to fellow unaffected eyes of patients with unilateral Fuchs' uveitis syndrome (FUS) and analyze their change over time. METHODS: Twenty seven unilateral FUS patients who did not have concomitant systemic or ocular disease were retrospectively enrolled. Central macular thickness (CMT), RNFL thickness, and GCIPLT measurements were evaluated. Data was analyzed using the non-parametric Brunner-Langer model (LD-F2 design) and Wilcoxon signed-rank test. RESULTS: The mean age of the patients was 40.2 ± 10.2 years. The median disease duration was 11 (2-62) months. The median best-corrected visual acuity (BCVA) of the affected eyes and the fellow eyes was 0.22 (0.00-2.50) vs. 0.00 (0.0-0.10) logMAR at the initial visit and 0.05 (0.00-2.50) vs. 0.00 (0.0-0.30) logMAR at the final visit. The change in BCVA was found significant in the affected eyes, but not in the fellow eyes (p < 0.001 and p = 0.287, respectively). The median CMT in the affected eyes at the final visit was not statistically different from the value at the initial visit (255 (157-306) vs. 245 (140-310) µm, p = 0.256). The change in RNFL thickness over time in the affected eyes was similar to the fellow unaffected eyes of the patients with unilateral FUS at all quadrants, with non-significant time and group effects (p > 0.05). However, median GCIPLT in all quadrants (except superonasal) in the affected eyes was statistically lower than the fellow eyes at the initial and final visits (p < 0.05). The most affected quadrant of the ganglion cell complex was inferonasal in the involved eyes (79 (42-97) vs. 75 (43-87) µm) at initial and final visits (p = 0.033 for time effect and p < 0.001 for group effect, respectively). CONCLUSION: Median CMT and RNFL thickness did not change during follow-up in the affected eyes of patients with unilateral FUS. Median GCIPLT in the affected eyes declined over time in all quadrants. Ganglion cell loss was also most prominent in the inferonasal quadrant in the affected eyes. FUS patients should be followed up long-term in terms of ganglion cell loss, especially in the inferonasal quadrant.

DRD4 genotyping may differentiate symptoms of attention-deficit/hyperactivity disorder and sluggish cognitive tempo

Objective: Studies to reduce the heterogeneity of attention-deficit/hyperactivity disorder (ADHD) have increased interest in the concept of sluggish cognitive tempo (SCT). The aim of this study was to investigate if the prevalence of two variable-number tandem repeats (VNTRs) located within the 3′-untranslated region of the DAT1 gene and in exon 3 of the dopamine D4 receptor (DRD4) gene differ among four groups (31 subjects with SCT but no ADHD, 146 individuals with ADHD but no SCT, 67 subjects with SCT + ADHD, and 92 healthy controls). Methods: We compared the sociodemographic profiles, neurocognitive domains, and prevalence of two VNTRs in SCT and ADHD subjects versus typically developing (TD) controls. Results: The SCT without ADHD group had a higher proportion of females and lower parental educational attainment. Subjects in this group performed worse on neuropsychological tests, except for psychomotor speed and commission errors, compared to controls. However, the ADHD without SCT group performed significantly worse on all neuropsychological domains than controls. We found that 4R homozygosity for the DRD4 gene was most prevalent in the ADHD without SCT group. The SCT without ADHD group had the highest 7R allele frequency, differing significantly from the ADHD without SCT group. Conclusion: The 7R allele of DRD4 gene was found to be significantly more prevalent in SCT cases than in ADHD cases. No substantial neuropsychological differences were found between SCT and ADHD subjects.

DRD4 genotyping may differentiate symptoms of attention-deficit/hyperactivity disorder and sluggish cognitive tempo.

OBJECTIVE: Studies to reduce the heterogeneity of attention-deficit/hyperactivity disorder (ADHD) have increased interest in the concept of sluggish cognitive tempo (SCT). The aim of this study was to investigate if the prevalence of two variable-number tandem repeats (VNTRs) located within the 3'-untranslated region of the DAT1 gene and in exon 3 of the dopamine D4 receptor (DRD4) gene differ among four groups (31 subjects with SCT but no ADHD, 146 individuals with ADHD but no SCT, 67 subjects with SCT + ADHD, and 92 healthy controls). METHODS: We compared the sociodemographic profiles, neurocognitive domains, and prevalence of two VNTRs in SCT and ADHD subjects versus typically developing (TD) controls. RESULTS: The SCT without ADHD group had a higher proportion of females and lower parental educational attainment. Subjects in this group performed worse on neuropsychological tests, except for psychomotor speed and commission errors, compared to controls. However, the ADHD without SCT group performed significantly worse on all neuropsychological domains than controls. We found that 4R homozygosity for the DRD4 gene was most prevalent in the ADHD without SCT group. The SCT without ADHD group had the highest 7R allele frequency, differing significantly from the ADHD without SCT group. CONCLUSION: The 7R allele of DRD4 gene was found to be significantly more prevalent in SCT cases than in ADHD cases. No substantial neuropsychological differences were found between SCT and ADHD subjects.

Adjunctive Effects of a Sub-Antimicrobial Dose of Doxycycline on Clinical Parameters and Potential Biomarkers of Periodontal Tissue Catabolism.

OBJECTIVES: The aim of the present randomized, double-blind, placebo-controlled, parallel-arm study was to examine the effectiveness of a sub-antimicrobial dose of doxycycline (SDD) in combination with nonsurgical periodontal therapy, compared to nonsurgical periodontal therapy alone, on potential gingival crevicular fluid (GCF) biomarkers of periodontal tissue catabolism related to the clinical outcomes over a 12-month period. Materials and Methods: GCF was collected and clinical parameters were recorded from 30 periodontitis patients randomized either to an SDD or placebo group. The SDD group received SDD (20 mg) b.i.d for 3 months plus scaling and root planing (SRP), while the placebo group was given placebo capsules b.i.d for 3 months plus SRP. The patients were evaluated every 3 months during the 12-month study period. At each visit, clinical parameters and GCF sampling were repeated. Matrix metalloproteinase (MMP)-8, MMP-9, MMP-13, myeloperoxidase (MPO), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase-5 (TRAP-5) were determined by IFMA and ELISA. Results: Significant improvements were observed in all clinical parameters in both groups over 12 months (p < 0.0125) while the SDD group showed significantly better reduction in gingival index (GI) and pocket depth and a gain in clinical attachment compared to the placebo group (p < 0.05). GCF MMP-8 and OPG levels significantly reduced in the SDD group compared to baseline (p < 0.05). GCF MMP-9 significantly decreased in both groups compared to baseline (p < 0.05). GCF MPO significantly decreased at 3 and 9 months in the SDD group, while it significantly decreased at 6 months in the placebo group (p < 0.05). TRAP and MMP-13 could be detected in none of the samples. Conclusions: The present results indicate that three months of adjunctive usage of SDD to nonsurgical periodontal therapy compared to nonsurgical periodontal therapy alone in periodontitis patients results in further improvement of clinical periodontal parameters and GCF markers of periodontal tissue breakdown over a 12-month period. Beneficial effects of adjunctive SDD therapy is likely to be related to the reduced levels of two major periodontitis-associated MMPs, MMP-8 and -9, and their potential oxidative activator MPO.

Deletions in SERPING1 Lead to Lower C1 Inhibitor Function: Lower C1 Inhibitor Function Can Predict Disease Severity.

BACKGROUND: How genotype affects phenotype in hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) has not been totally clarified. In this study, we investigated the relationship between different types of mutations and various phenotypic characteristics. METHODS: Clinical data from 81 patients from 47 families were recorded. Complement proteins were analyzed from 61 untreated patients. The coding exons and the exon-intron boundaries of the SERPING1 gene were sequenced, and deletion/duplication analysis with multiple ligation dependent probe amplification was performed. The relationship of complement protein with the mutation type was analyzed by using generalized estimating equations. RESULTS: Thirty-five different mutations (15 novel and 2/15 homozygous) were identified. There was no causative mutation in 6 patients (7.4%). Patients with deletion and large deletion had the lowest (5.05%, 0-18.7; 5.8%, 0-16.5%, respectively), and the none mutation group had the highest C1 inhibitor function (23.3%, 11-78%, p < 0.001). C1 inhibitor function levels decreased as the age of the disease progressed (r = -0.352, p = 0.005). Lower C1 inhibitor function levels caused severer disease (r = -0.404, p = 0.001) and more frequent annual attacks (r = -0.289, p = 0.024). In the off-attack period, C1q levels were lower than normal in 9.8% of the patients. CONCLUSION: Deletion mutations may represent the most unfavorable effect on C1 inhibitor function. The earlier disease onset age could be a sign for lower C1 inhibitor function levels in adult life. C1q levels could also be low in C1-INH-HAE patients, as in acquired angioedema. Lower C1 inhibitor function can predict disease severity and may have negative impacts on the course of C1-INH-HAE.