Previous studies have established that disturbed lymphocytes are involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) syndrome. Accordingly, glucocorticoids (GCs), with their well-recognized immune-suppressive function, have been widely used for treatment of VKH patients with acute relapses. However, the systemic response of diverse immune cells to GC therapy in VKH is poorly characterized. To address this issue, we analyzed immune cell subpopulations and their phenotype, as well as cytokine profiles in peripheral blood from VKH patients (n=25) and health controls (HCs, n=21) by flow cytometry and luminex technique, respectively. For 16 patients underwent GC therapy (methylprednisolone, MP), the aforementioned measurements as well as the transcriptome data from patients before and after one-week’s GC therapy were also compared to interrogate the systemic immune response to GC therapy. Lymphocyte composition in the blood was different in VKH patients and HCs. VKH patients had significantly higher numbers of T cells with more activated, polarized and differentiated phenotype, more unswitched memory B cells and monocytes, as compared to HCs. MP treatment resulted in decreased frequencies of T cells and NK cells, inhibited NK cell activation and T cell differentiation, and more profoundly, a marked shift in the distribution of monocyte subsets. Collectively, our findings suggest that advanced activation and differentiation, as well as dysregulated numbers of peripheral lymphocytes are the major immunological features of VKH, and GC therapy with MP not only inhibits T cell activation directly, but also affects monocyte subsets, which might combinatorically result in the inhibition of the pathogenic immune response.
Background. Rhegmatogenous retinal detachment associated with choroidal detachment (RRDCD) is rare and the prognosis is poor. This retrospective study evaluated the effect of preoperative steroid on the clinical outcome of patients with RRDCD receiving 23-gauge pars plana vitrectomy (PPV). Methods. Sixty-six patients (67 eyes) with diagnosed RRDCD underwent 23-gauge PPV. The patients assigned to receive systemic or subtenon injection of preoperative steroids were considered Group A (35 eyes) and did not receive are considered Control Group B (32 eyes). Most patients in Group A received subtenon injection of glucocorticoids. The cyclodialysis angle was measured with ultrasound biomicroscopy. Preoperative, intraoperative, and postoperative data were compared. Results. The rates of retinal reattachment in Group A after the first and second operations were 68.8% (24/35 eyes) and 91.43% (32/35 eyes), respectively, which were not significantly different from that of Group B (78.1%, 25/32 eyes; 96.6%, 31/32 eyes). The logMAR (logarithm of the minimum angle of resolution) visual acuity in Group A (1.63 ± 0.75) was similar to that of Group B (1.34 ± 0.74). Postoperative intraocular pressure and ocular hypertension in Group A (17.94 ± 9.82 mmHg and 37.1%, respectively; 13/35 eyes) were comparable to that of Group B (20.93 ± 10.21 mmHg and 56.3%; 18/32 eyes). Logistic regression analysis showed that postoperative reattachment was negatively associated with preoperative cyclodialysis angle as measured with ultrasound biomicroscopy () but was not significantly associated with preoperative steroid use (). Conclusions. Preoperative steroid use does not improve retinal reattachment and visual acuity in patients with RRDCD after 23-gauge PPV. Preoperative measurement of the cyclodialysis angle with ultrasound biomicroscopy may be useful for predicting clinical outcomes.
1 February 2014 in Journal of Laparoendoscopic & Advanced Surgical Techniques
Background: Even though laparoscopic cholecystectomy (LC) emerged over 20 years ago, controversies persist with regard to the best method to ligate the cystic duct and artery. We proposed to assess the effectiveness and safety of electrocoagulation to seal the cystic artery and cystic duct after their occlusion with only one absorbable clip. Materials and Methods: We retrospectively compared the clinical data for 635 patients undergoing LC using electrocoagulation to seal the cystic artery and cystic duct that were occluded with only one absorbable clip (Group 1) and 728 patients undergoing LC using titanium clips (Group 2). In parallel, 30 rabbits randomized into six groups underwent cholecystectomy. After cystic duct ligation with absorbable or titanium clips, the animals were sacrificed 1, 3, or 6 months later, and intraabdominal adhesions were assessed after celiotomy. Results: The mean operative time was significantly shorter (41.6 versus 58.9 minutes, P <.01) in Group 1 than in Group 2. No cystic duct leaks occurred in any patients from Group 1, compared with seven leaks among the 728 (0.96%) patients from Group 2 ( P <.05). The morbidity was significantly higher in Group 2 than in Group 1 (3.43% versus 1.58%). Mean intraoperative blood loss and hospitalization length were not significantly different between the two groups, and no deaths occurred in either group. In animal experiments, adhesion was tighter for absorbable than for titanium clips, but fibrous tissue encapsulation was thinner at the site of titanium clips. Conclusions: Electrocoagulation of the cystic artery and cystic duct that were occluded with only one absorbable clip is safe and effective during LC. This approach is associated with shortened operative times and reduced leakage, compared with the standard method using metal clips.
Axenfeld–Rieger syndrome (ARS) is an uncommon manifestation of anterior segment development dysregulation. We recruited a two-generation Chinese family with hereditary ARS, which manifested as posterior embryotoxon, corneal leucoplakia, ectopic pupil, and extensive iris stromal atrophy with iridocorneal adhesion. Whole-exome sequencing (WES) was utilized for the initial screening, followed by Sanger sequencing to identify pathogenic gene mutations. A novel missense variant in FOXC1 (c.382C > T, p.H128Y) was identified. The FOXC1 protein is highly evolutionarily conserved. The potential effects of this mutation on protein structure were studied using 3D modelling and molecular dynamics (MD) simulation techniques. 3D modelling revealed that the mutation altered the conformation of the FOXC1 protein. The MD results suggested that the mutation could reduce the stability of the protein structure. Western blotting revealed that the expression of the mutant FOXC1 (c.382C > T, p.H128Y) was lower than that of the wild type. In summary, a novel FOXC1 variant was discovered within a Chinese family with ARS, broadening the spectrum of ARS mutations. This study also elucidated the underlying mechanisms by which FOXC1 gene deficiency causes ARS.