Background and objective Primary ciliary dyskinesia (PCD) is a rare and genetically heterogeneous disease and the severity of the disease related with genetic analysis has been described in some previous studies. The main aim of our study was to describe the clinical characteristics and laboratory findings of patients with genetically diagnosed PCD and to investigate the correlation between clinical, radiologic, and laboratory findings and genetic analyses of these patients. Method This is a cohort study in which we analyzed the clinical characteristics, laboratory findings, and genetic results of 46 patients with genetically diagnosed PCD through whole‐exome sequencing at our single center from a total of 265 patients with PCD within a 5‐year period. Results Genetic analysis revealed pathogenic variants in DNAH5 (n = 12 individuals, 12 families), CCDC40 (n = 9 individuals, six families), RSPH4A (n = 5 individuals, three families), DNAH11 (n = 4 individuals, four families), HYDIN (n = 5 individuals, five families), CCNO (n = 4 individuals, four families), DNAI1 (n = 2 individuals, one family), ARMC4 (n = 2 individuals, two families), TTC25 (n = 1), DNAH1 (n = 1), and CCDC39 (n = 1) genes. Although not statistically significant, the age at diagnosis was lower (median: 3 years; range, 6 months‐4 years) in patients with CCNO pathogenic variants due to the early reporting of symptoms, and the median body mass index (BMI) and BMI z scores were lower in patients at 18.7 and 16 kg/m2, and −0.78 and −1.2 with CCDC40 and CCNO pathogenic variants, respectively. The median forced expiratory flow in 1 second (FEV1%), forced vital capacity (FVC%), and forced expiratory flow (FEF)25‐75% were 53%, 64%, and 28%, respectively; these parameters were also lower in the CCDC40 group than in the other groups. There was no significant correlation between the genetic results and symptoms, radiologic findings, and microbiologic data of patients with PCD. Conclusion In PCD, there was significant heterogeneity of lung disease, patients who had pathogenic variants in CCNO presented earlier, and those with CCDC40 and CCNO had worse lung disease, and poorer nutritional status compared with the other subgroups. We hope that whole genotype‐phenotype and clinical relationships will be identified in PCD.

Purpose: To evaluate light microscopy and transmission electron microscopy findings of levator muscle/aponeurosis materials and their correlation with clinical findings in isolated congenital myogenic and aponeurotic blepharoptosis. Methods: Demographic and clinical data were obtained from patients. Qualitative and quantitative evaluations for muscle fiber morphology were performed using light microscopy and transmission electron microscopy on tissue samples which were obtained from the most proximal part of the aponeurosis excised during levator muscle/aponeurosis resection surgery. Results: Seventeen (55%) of the cases were isolated congenital myogenic ptosis, and 14 (45%) were aponeurotic ptosis. Muscle bundle splitting, cytoplasmic loss, and centrally located nuclei were observed in both groups. Muscle tissue covered 25% of the sample in 67% of the cases, 50% in 11%, 75% in 11%, and 100% in 11% in the myogenic group. In the aponeurotic group, muscle tissue covered 25% of the sample in 44.5% of the cases, 50% in 11%, and 100% in 44.5% (χ 2, p = 0.52). Myofibrillar loss areas accompanied by Z-line disorganization which were occupied by degenerated organelles were present in both groups under transmission electron microscopy, and findings were not significantly different between groups (χ 2, p > 0.05). Mean mitochondrial diameter was significantly larger in aponeurotic ptosis (Mann-Whitney U, p = 0.047). No correlation was found between functional and microscopic parameters. Conclusion: Decreased amount of striated muscle and the presence of fiber damage indicators were observed in both groups. Muscle fiber loss in myogenic ptosis may be a feature of muscle dysgenesis. Ultrastructural damage in aponeurotic ptosis may be explained with increased oxidative stress or long-term contractile stress. Further genetic and immunohistochemical studies will be helpful to further understand the pathogenesis of diseases.

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Background Our objective was to investigate an abbreviated version of the the current European PH guidelines, noninvasive French model, an abridged version of the REVEAL 2.0 risk score calculator, REVEAL Lite 2, and a refined 4-strata risk assessment model, COMPERA 2.0 for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Methods We enrolled inoperable CTEPH patients from 8 PAH centers from December 2009 to June 2020 (n=123). 70% of patients were treated with PAH therapies. Noninvasive French model comprising WHO functional class (FC), 6-minute walk distance (6 MWD), and N-terminal pro–brain natriuretic peptide (NT-pro BNP) or BNP was used for 63 patients. REVEAL Lite 2 including FC, systolic blood pressure, heart rate, 6MWD, BNP/NT-pro BNP, and estimated glomerular filtration rate was used for 71 patients. COMPERA 2.0 including FC, 6MWD and BNP/NT-pro BNP was used for 71 patients. Patients were grouped into three categories according to the French model and REVEAL Lite 2 scores, and into four categories according to COMPERA 2.0. Kaplan-Meier (KM) survival was assessed in each risk group with all-cause mortality as the end point. Log-rank test was used to compare estimates. Results The mean age was 64±13 years at diagnosis. The median follow-up was 22.7 months. 26 patients had died. None of the patients had balloon pulmonary angioplasty. Most patients had received monotherapy (55%). 23.8% of patients were WHO FC I-II, 65.6% III, and 10.7% IV at initial evaluation (Table 1). All models discriminated risk in our cohort. Patients having none of low-risk criteria or high risk profiles by REVEAL Lite 2 and COMPERA 2.0 at follow-up had the worst survival. Figure 1 demonstrates KM survival curves for noninvasive French model (A), REVEAL Lite 2 (B), and COMPERA 2.0 (C). 37.3% of patients achieved 2 or more low risk criteria at follow-up. 44.8% of patients were in low risk at follow-up (REVEAL lite 2). 52.1% of patients were in low and intermediate-low risk at follow-up (COMPERA 2.0). The estimated survival rate at 5 years of patients meeting 2 and more low-risk criteria was 86% vs. 55% for patients meeting 0 low-risk criterion (p=0.04). The corresponding survival rate was 45% for high-risk patient, 79% for intermediate-risk patient, and 82% for low-risk patient (REVEAL lite 2) (p=0.029). The corresponding survival rates were 51.1% for high-risk patient and 91.6% for intermediate-low risk patient (COMPERA 2.0) (p=0.017). COMPERA 2.0 seems more accurate based on c-index. Survival was similar between patients treated and not treated with PAH therapies (p=0.735). Conclusions Noninvasive French model, REVEAL Lite 2, and COMPERA 2.0 may provide a simplified method of risk assessment for inoperable CTEPH. This analysis also supports the value of goal-oriented treatment in CTEPH. Patients who have not achieved low risk category at follow-up may benefit from escalation of their treatment regimen. Funding Acknowledgement Type of funding sources: None.

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