Structural basis of microRNA biogenesis by Dicer-1 and its partner protein Loqs-PB.

In animals and plants, Dicer enzymes collaborate with double-stranded RNA-binding domain (dsRBD) proteins to convert precursor-microRNAs (pre-miRNAs) into miRNA duplexes. We report six cryo-EM structures of Drosophila Dicer-1 that show how Dicer-1 and its partner Loqs­PB cooperate (1) before binding pre-miRNA, (2) after binding and in a catalytically competent state, (3) after nicking one arm of the pre-miRNA, and (4) following complete dicing and initial product release. Our reconstructions suggest that pre-miRNA binds a rare, open conformation of the Dicer­1⋅Loqs­PB heterodimer. The Dicer-1 dsRBD and three Loqs­PB dsRBDs form a tight belt around the pre-miRNA, distorting the RNA helix to place the scissile phosphodiester bonds in the RNase III active sites. Pre-miRNA cleavage shifts the dsRBDs and partially closes Dicer-1, which may promote product release. Our data suggest a model for how the Dicer­1⋅Loqs­PB complex affects a complete cycle of pre-miRNA recognition, stepwise endonuclease cleavage, and product release.

Prevention of nostril lacerations in endonasal drilling procedures by use of a conventional protective ear speculum.

PURPOSE: Injuries of the nasal vestibular skin caused by the rotating burr shafts can represent a tedious complication following endonasal drilling and is experienced sooner or later by every rhino-surgeon. MATERIAL AND METHODS: To protect the nasal entrance from laceration by the free rotating drill shaft we position an otology speculum in the nasal entrance. The speculum is held in place by the scrub nurse during the critical phase of bone drilling. RESULTS: Following the introduction of the ear speculum protection, we successfully treated our dacryocystostamia procedures (n = 27) and median maxillectomia procedures (n = 6) without any further soft tissue erosions. DISCUSSION: Preventive measures for injuries by endonasal drilling procedures are not reported extensively in literature. This stands in contrast to the fact that these injuries are prone to cause significant suffering as amply described in the case of nostril laceration due to nasogastric intubation or nasogastric feeding tubes. CONCLUSION: The use of a readily available, reusable ear speculum in endonasal drill application eliminated the complication of nasal entrance lacerations throughout our institution, hitherto.

Practice patterns in revision dacryocystorhinostomy.

PURPOSE: This study aimed to report the practice patterns while performing revision dacryocystorhinostomy (RevDCR) amongst oculoplastic surgeons from several regions across the globe. METHODS: The survey consisted of 41 specific questions sent via email that contained a link to the Google forms. The questions covered several aspects of the respondents' practice profiles, evaluation methods, pre-operative choices, surgical techniques, and follow-up preferences while dealing with patients of prior failed DCRs. Questions were answerable either as multiple choice or free text typing. The survey respondents were anonymized. The responses were collected and analyzed, and data were tabulated to understand the preferred practice trends. RESULTS: A total of 137 surgeons completed the survey. Most respondents identified themselves as experienced surgeons managing failed DCRs (76.6%, total respondents (n) = 137). The commonly preferred modalities for evaluation of a failed DCR were lacrimal irrigation (91.2%) and nasal endoscopy (66.9%). About 64% (87/137) of the respondents performed a combination of nasal endoscopy, lacrimal irrigation, and probing to localize the area of the failed DCR. A majority of the respondents used anti-metabolites (73.3%, n = 131) and stents (96.4%, 132/137) during the revision surgery. Most surgeons preferred endoscopic approach (44.5%), (61/137) for revising a failed DCR and most preferred general anaesthesia with local infiltration (70.1%, 96/137). Aggressive fibrosis with cicatricial closure was identified as the most frequently encountered cause of failure (84.6%, 115/137). The osteotomy was performed on an as-needed basis by 59.1% (81/137) of the surgeons. Only 10.9% of the respondents used navigation guidance while performing a revision DCR, mainly for post-trauma scenarios. Most of the surgeons completed the revision procedure within 30-60 minutes (77.4%, 106/137). The self-reported outcomes of revision DCRs were good (80-95%, median-90%, n = 137). CONCLUSION: A significantly high percentage of oculoplastic surgeons who responded to this survey from across the globe performed nasal endoscopy in their pre-operative evaluations, preferred endoscopic surgical approach, and used antimetabolites and stents while performing revision DCRs.

Medial lacrimal sac excision versus conventional H-shaped lacrimal sac opening in external dacryocystorhinostomy: a comparative cohort study.

PURPOSE: The external dacryocystorhinostomy (Ex-DCR) is a reliable but surgically challenging procedure to overcome a nasolacrimal duct obstruction (NLDO). The aim of this study is to describe the outcomes of a modified technique of lacrimal sac opening and to compare it with the conventional Ex-DCR. METHODS: This comparative cohort study included adult patients undergoing Ex-DCR for primary acquired NLDO by or under supervision of one surgeon. Group 1 (conventional Ex-DCR including H-shaped incision, anastomosis of the anterior mucosal flap to nasal mucosal flap and resection of the posterior sac flap) was compared with Group 2 (modified Ex-DCR including excision of the medial lacrimal sac and anastomosis of remaining anterior sac flap to nasal mucosal flap). Outcome measures included the success rate (defined as complete symptom relief or patent irrigation after three months), reoperation rate, redo-free survival within five years, and occurrence of postoperative bleeding and postoperative infection. RESULTS: 138 patients were included. The success rates were 94.7% (54/57 cases) for Group 1 and 96.3% (78/81) for Group 2 (p-value = 0.658). The redo-rate was 5.3% (3/75) in Group 1 and 2.5% (2/81) in Group 2 (p = 0.331). Two-year redo-free survival probability estimates were 89.8% for Group 1 and 96.3% for Group 2, respectively. No complications occurred in Group 2, whereas in Group 1, one patient (1.8%) suffered from postoperative bleeding and one (1.8%) from postoperative infection. CONCLUSIONS: This study showed that our modified Ex-DCR technique is equally efficacious compared with the conventional Ex-DCR technique in adult patients with NLDO.

Prospective, randomised clinical trial on the necessity of using a silicone intubarium in the context of endonasal-endoscopic dacryocystorhinostomy (EN-DCR) in patients with postsaccal lacrimal duct stenosis.

BACKGROUND: This prospective clinical study evaluates the effect of a silicone stent tube (SST) on the success rate of endonasal-endoscopic dacryocystorhinostomy (EN-DCR) to treat primary acquired nasolacrimal duct obstruction. METHODS: Patients were randomly assigned to receive EN-DCR with or without SST intubation over a period of 3 months. The surgery was performed using standardized techniques. Patients were assessed at three different timepoints: one day, 12 weeks and 24 weeks after the surgery. The results were compared in order to evaluate statistical differences. Surgical success was determined by means of positive irrigation procedures, as well as by the improvement of symptoms and a high level of patient satisfaction. RESULTS: A total of 56 randomized cases completed 24 weeks of follow up. 1 Patient dropped out due to malignant genesis of the nasolacrimal duct obstruction. After 24 weeks of follow up no statistically significant differences in levels of epiphora (p > .10) or patency (p > .16) were revealed. Comparisons regarding changes in time did not show levels of significance (p > .28). CONCLUSIONS: This study could not confirm a statistically significant benefit or disadvantage for SST Insertion in EN-DCR.

[Pharmacological prevention of fibrosis in dacryosurgery]. / Medikamentoznaya profilaktika fibrotizatsii v dakriokhirurgii.

Chronic inflammatory process in the lacrimal drainage system is the main etiological factor leading to dacryostenosis and consequent obliteration - partial and total nasolacrimal duct obstruction. Prevention of this process is an urgent problem in dacryology. Currently, there is very little research on the development and use of conservative methods for treating dacryostenosis using anti-inflammatory, as well as anti-fibrotic drugs. In this regard, the main method of treating lacrimal drainage obstruction is dacryocystorhinostomy. However, the problem of recurrence after this operation has not been resolved. The causes of recurrence can be cicatricial healing of dacryocystorhinostomy ostium, canalicular obstruction, formation of granulations and synechiae in its area. Surgical methods of recurrence prevention are associated with possible complications, and there is conflicting data on the feasibility of their use. Based on this, the development of pharmacological methods for the prevention of fibrosis in dacryology is promising, among which the antitumor antibiotic Mitomycin C is the most studied. However, there are no specific scientifically substantiated recommendations for the use of this drug, and the data on its effectiveness vary. This has prompted researchers to look for and study alternative anti-fibrotic agents, such as antitumor drugs, glucocorticoids, hyaluronic acid, small molecule, biological, immunological and genetically engineered drugs, as well as nanoparticles. This review presents the current data on the efficacy and prospects of the use of these drugs in dacryology.

Success rate of external, endonasal, and transcanalicular laser DCR with or without silicone stent intubation for NLD obstruction: a network meta-analysis of randomized controlled trials.

PURPOSE: To define and compare the effectiveness of external dacryocystorhinostomy (EX-DCR), endonasal (EN-DCR), and transcanalicular laser-assisted (TL-DCR) with or without silicone stent (S) intubation. METHODS: Studies were retrieved from PubMed, Scopus, and WoS. Frequentist and Bayesian network meta-analyses were performed and pooled estimations were expressed as risk ratio (RR). We included all original investigations of prospective, randomized controlled trials comparing success rate for any two of the following six surgical procedures: standard EX-DCR with or without S, cold EN-DCR with or without S, and TL-DCR with or without S. The primary outcome measure was the objective success rate. RESULTS: Thirty-two studies with 3277 cases were included in the final quantitative analysis. TL-DCR with S was inferior to EN-DCR with S (RR: 1.20; 95% CI: 1.05-1.37), EX-DCR with S (RR: 1.17 95% CI: 1.05-1.29), EN-DCR without S (RR: 1.18; 95% CI: 1.03-1.35), and EX-DCR without S (RR: 1.15; 95%CI: 1.05-1.26) in frequentist statistics. No other statistical difference was found between other surgeries. When we excluded studies with additional interventions (nasal and revision surgery) for sensitivity analysis, 23 studies with 2468 cases were included to analysis. The success rates of TL-DCR with S and EN-DCR without S became similar (RR: 1.14 95% CI: 0.99-1.30) but there was no change in other outcomes. Similar results were found in Bayesian statistics. The surface under the cumulative ranking curve was higher for EN-DCR with S (0.75), whereas it was higher for EX-DCR with S (0.56) after sensitivity analysis. CONCLUSION: Between endoscopic and external and transcanalicular laser without S procedures, there is no statistical difference. The rank probability showed that EN-DCR with S was a more appropriate surgical option when patients with nasal disease were included, whereas EX-DCR with S was a more appropriate surgical option when patients with nasal disease were excluded from the analysis.

Lightweight Network DCR-YOLO for Surface Defect Detection on Printed Circuit Boards.

To resolve the problems associated with the small target presented by printed circuit board surface defects and the low detection accuracy of these defects, the printed circuit board surface-defect detection network DCR-YOLO is designed to meet the premise of real-time detection speed and effectively improve the detection accuracy. Firstly, the backbone feature extraction network DCR-backbone, which consists of two CR residual blocks and one common residual block, is used for small-target defect extraction on printed circuit boards. Secondly, the SDDT-FPN feature fusion module is responsible for the fusion of high-level features to low-level features while enhancing feature fusion for the feature fusion layer, where the small-target prediction head YOLO Head-P3 is located, to further enhance the low-level feature representation. The PCR module enhances the feature fusion mechanism between the backbone feature extraction network and the SDDT-FPN feature fusion module at different scales of feature layers. The C5ECA module is responsible for adaptive adjustment of feature weights and adaptive attention to the requirements of small-target defect information, further enhancing the adaptive feature extraction capability of the feature fusion module. Finally, three YOLO-Heads are responsible for predicting small-target defects for different scales. Experiments show that the DCR-YOLO network model detection map reaches 98.58%; the model size is 7.73 MB, which meets the lightweight requirement; and the detection speed reaches 103.15 fps, which meets the application requirements for real-time detection of small-target defects.

Modeling for Single-Photon Avalanche Diodes: State-of-the-Art and Research Challenges.

With the growing importance of single-photon-counting (SPC) techniques, researchers are now designing high-performance systems based on single-photon avalanche diodes (SPADs). SPADs with high performances and low cost allow the popularity of SPC-based systems for medical and industrial applications. However, few efforts were put into the design optimization of SPADs due to limited calibrated models of the SPAD itself and its related circuits. This paper provides a perspective on improving SPAD-based system design by reviewing the development of SPAD models. First, important SPAD principles such as photon detection probability (PDP), dark count rate (DCR), afterpulsing probability (AP), and timing jitter (TJ) are discussed. Then a comprehensive discussion of various SPAD models focusing on each of the parameters is provided. Finally, important research challenges regarding the development of more advanced SPAD models are summarized, followed by the outlook for the future development of SPAD models and emerging SPAD modeling methods.

Emerging Role of Decoy Receptor-2 as a Cancer Risk Predictor in Oral Potentially Malignant Disorders.

The aim of this study was to evaluate the expression of the senescence markers, Decoy Receptor 2 (DcR2) and Differentiated Embryo-Chondrocyte expressed gen 1 (DEC1), in oral potentially malignant disorders (OPMDs) to ascertain their possible association with oral cancer risk. The immunohistochemical analysis of DcR2 and DEC1 expression (along with p16 and Ki67 expression) was carried out in 60 patients with clinically diagnosed oral leukoplakia. Fifteen cases (25%) subsequently developed an invasive carcinoma. Correlations between protein marker expression, histological grade and oral cancer risk were assessed. DcR2, DEC1 and Ki67 protein expressions were found to correlate significantly with increased oral cancer risk, and also with an increased grade of dysplasia. Multivariate analysis demonstrated that DcR2 and Ki67 expression are independent predictors of oral cancer development. Our results evidence for the first time the potential of DcR2 as an early biomarker to assess oral cancer risk in patients with oral leukoplakia (HR = 59.7, p = 0.015), showing a superior predictive value to histology (HR = 4.225, p = 0.08). These findings reveal that the increased expression of DcR2 and DEC1 occurred frequently in OPMDs. In addition, DcR2 expression emerges as a powerful biomarker for oral cancer risk assessment in patients with oral leukoplakia.

Reversed total shoulder arthroplasty after acromioclavicular joint resection yields equivalent clinical results compared to a matched control group.

INTRODUCTION: Reverse total shoulder arthroplasty (RTSA) is a well-establish procedure with increasing incidence. Depending on the medical history, many patients undergo multiple soft-tissue procedures before RTSA. The role of acromioclavicular pathology as well as the consequences of a distal clavicle resection (DCR) before RTSA has not been evaluated yet. MATERIAL AND METHODS: A retrospective single-center review was performed on all patients undergoing primary RTSA with or without DCR with a minimum follow-up of 2 years. We compared patient-reported outcome measures (Constant score (CS), subjective shoulder values (SSV), and range of motion (ROM)) with a matched control group. The control group consisted of patients treated with a RTSA without DCR and matching was performed for age, sex, operating side, American Society of Anesthesiologists (ASA), body mass index (BMI), and indication. Surgical time and complication rate were recorded. RESULTS: Thirty-nine patients with a mean follow-up of 63 months (SD 33) were enrolled in the study group. Mean age was 67 years (SD 7) with 44% male patients for both groups. The mean relative CS improved from 43% (SD 17) to 73% (SD 20) in the study group, and from 43% (18) to 73% (22) in the control group. The SSV improved from 29% (SD 17) to 63% (SD 29) in the study group, and from 28% (SD 16) to 69% (SD 26) in the control group (both n.s.). The postoperative ROM did not significantly differ between the two groups. Five patients in the study group and six in the control group had reoperations. CONCLUSION: Patients who received a DCR before RTSA showed equivalent clinical outcomes compared to a match-control group with RTSA only. Surgical time was not different, and no complication related to the open DCR was observed in the study group. Therefore, we conclude that a prior DCR does not influence the postoperative outcome after RTSA. LEVEL OF EVIDENCE: Level III: Retrospective comparative study.

Long-term outcomes of StopLoss™ Jones tube (SLJT) and minimally invasive conjunctivodacryocystorhinostomy.

PURPOSE: To assess the long-term outcomes of minimally invasive conjunctivodacryocystorhinostomy (MICDCR) with StopLoss™ Jones tubes. METHODS: A retrospective interventional case series was performed on all patients who underwent a MICDCR with StopLoss™ Jones tubes (SLJT) over a period of 5 years. Patients were followed for a minimum of 1 year after surgery. The parameters studied include patient demographics, clinical presentation, indication for MICDCR, duration of surgery, SLJT length, standard Jones tube drainage classification, complications, and anatomical and functional successes. The variables influencing the outcomes were assessed. Anatomical success was defined as patent SLJT on irrigation, and functional success was defined as resolution of epiphora. Statistical analysis was performed using the R 4.0.4 (R Project, R Foundation). RESULTS: A total number of 44 eyes of 42 patients were studied. The mean age of patients was 61.81 years. Approximately 87% and 64% of the patients completed 2 years and 3 years of follow-up, respectively. The Jones tube drainage class dipped significantly from class I to others at the 3-month follow-up. Classes III and IV dominated the follow-up period between 3 and 18 months, and class II dominated at 24 months and beyond. The anatomical and functional successes at the end of 1-year follow-up were 77.2%. The success was not affected by age, gender, length of SLJT tube, or duration of the surgery. However, the middle turbinate reduction influenced the success (P < 0.03). The common complications noted were tube occlusions (40.9%, 18/44) and inferior tube migration (38.6%, 17/44). CONCLUSION: The long-term outcomes with SLJT were good, but the inferior migration was a significant complication. The results of this study reflect the need for continuity of care as long as the tube is in situ.

Results and clinical aspects of primary endonasal endoscopic dacryocystorhinostomy with silicone tube.

OBJECTIVE: Endonasal endoscopic dacryocystorhinostomy (DCR) is a common treatment for saccal and post-saccal stenosis of the lacrimal pathway or chronic dacryocystitis (DC). The main symptom is chronic epiphora (tearing) and dacryocystitis (infection). The objective of this study is to assess the short-term surgical result of this treatment based on possible prognostic factors; such as gender, age, the pathogen spectrum and the histopathological result as well as the influence of these parameters on hospital stay. METHODS: It is a retrospective analysis, which includes 197 cases in 177 patients, who received an endonasal endoscopic DCR with a silicone tube between January 2009 and December 2016, as primary procedure. The follow-up was carried out 3 months after the surgery, with the silicone tube being removed as part of the last examination including a flushing of the tear ducts with saline. This procedure is part of determining to measure the short-term success of the intervention. The definition of success of the surgery is an absence of epiphora or an acute infection of the nasolacrimal duct system, as well as an absent reflux in case of flushing the tear duct. RESULTS: The success rate was 86.3% (N = 170). Higher incidence was seen in females (N = 146; 74.1%) and patients with a mean age of 65.4 (± 17.2). The presence of pathogens as well as the histopathological result do not have an impact on the short-term surgical success. Patients diagnosed with rheumatic diseases appear to have a worse prognosis with relation to procedure success. Also, the length of hospital stay was related to possible prognostic factors. Type II diabetes and glaucoma had a significant influence on a longer hospital stay. CONCLUSION: The endonasal endoscopic DCR is a surgical procedure with high success rate. Patients with rheumatic diseases should be aware of increased failure rates. Patients with glaucoma and Type II diabetes might need a more intense aftercare.

Long-term outcomes of primary transcanalicular laser dacryocystorhinostomy.

PURPOSE: To assess the long-term outcomes of transcanalicular laser dacryocystorhinostomy in cases of primary acquired nasolacrimal duct obstruction (PANDO). METHODS: Retrospective interventional case series was performed on all patients diagnosed with PANDO and who underwent a primary transcanalicular laser dacryocystorhinostomy from Jan 2014 to June 2016. The procedure was performed using 980 nm diode laser. All the patients additionally underwent intraoperative adjunctive procedures: mitomycin C application and silicone intubation. Patients were followed for up to 3 years after surgery. Anatomical success was defined as patent ostium on irrigation, and functional success was defined as resolution of epiphora. The parameters studied include patient demographics, clinical presentation, type of anesthesia, duration of surgery, laser energy delivered, complications, and anatomical and functional success. The variables influencing the outcomes were assessed. Statistical analysis was performed using the package Statistica (version 10.0, Statsoft, Poland). RESULTS: A total number of 205 patients were assessed. Of these, 73.17% (150/205) were females. The mean age of patients was 62.92 years. The mean laser energy used was 1060.09 J, and the mean operating time was 22.33 min. Approximately, 95% and 68% of the patients completed 1 year and 3 years of follow-up, respectively. The anatomical and functional success rates dropped significantly beyond the 3 months and 6 months postoperative period and maintained the lower success rates beyond 1-year follow-up for up to 3 years. The anatomical and functional success at the end of 3-year follow-up was 56.12% and 33.81%, respectively. The functional success was not affected by gender (P = 0.132), age (P = 0.956), laser energy (P = 0.626), or duration of the surgery (P = 0.906). However, the intraoperative pain scale was influenced by the laser energy (P < 0.001) and the duration of the surgery (P < 0.001). CONCLUSION: The anatomical and functional outcomes of primary transcanalicular laser dacryocystorhinostomy are suboptimal and not encouraging in the long term.

Mechanical transnasal endoscopic dacryocystorhinostomy versus transcanalicular multidiode laser dacryocystorhinostomy: long-term results of a prospective study.

The purpose of this study is to compare two dacryocystorhinostomy (DCR) techniques in epiphora treatment. This study is a prospective randomized trial. Twenty-nine patients presenting persistent epiphora due to primary acquired nasolacrimal duct obstruction (PANDO) were included in the study. Two groups each consisting of 15 eyes were formed. Mechanical transnasal endoscopic DCR (MTE-DCR) was applied to the first group, while transcanalicular dacryocystorhinostomy with multidiode laser (TCML-DCR) techniques is employed in the second group. Follow-up is conducted in the first day, first week, and first month of the dacryocystorhinostomy which is followed by 4-month follow-up period, and results were compared using statistical methods. The main outcome measures were the elimination of epiphora and unrestricted flow of irrigated saline to the nose. Seven patients were male, 22 were female, and the mean age was 39.3 ± 12.5 years. Mean follow-up times were 111.3 ± 10.5 months and 93 ± 2.9 months in group 1 and group 2, respectively. Complete resolution is achieved in group 1, whereas failures stemming from canalicular stenosis and fibrosis at osteotomy site are recorded in two cases in group 2. Occlusion occurred in the fifth month in both cases. Thus, long-term success rates were 100% in the first and 86.6% in the second group (P = 0.483). MTE-DCR is a strong substitute for external DCR. Although TCML-DCR shows promising results, it is far away from becoming the gold standard technique in epiphora treatment.

Lacrimal drainage system involvement in Peters anomaly: clinical features and outcomes.

PURPOSE: To present first of its kind series on the clinical features and outcomes of lacrimal drainage disorders in Peters anomaly and Peters plus syndrome. METHODS: A retrospective chart review was performed of all consecutive patients who were known cases of Peters anomaly or Peters plus anomaly and were diagnosed with associated congenital lacrimal drainage disorders. The study period was from June 2016 to Dec 2020. All these patients underwent examination under anaesthesia for a detailed assessment of lacrimal drainage anomalies. Where indicated, they were treated with probing, intubation, or in refractory patients with a dacryocystorhinostomy. The anatomical and functional outcomes were assessed. RESULTS: Of the 282 patients with Peters anomaly, 4 (1.4%) patients had associated lacrimal drainage system anomalies while of the 16 Peters plus anomaly children, 3 (18.75%) had associated lacrimal drainage system anomalies. A total of 12 lacrimal drainage systems of 12 eyes of 7 patients of Peters anomaly were found to be involved. Upper or lower punctal agenesis were noted in 3 eyes. Three eyes had complex congenital nasolacrimal duct obstruction (CNLDO), two of which had a bony NLD block and one had a misdirected nasolacrimal duct through the inferior turbinate. One eye had a diffuse NLD stenosis without a CNLDO. Following appropriate management, at a mean follow-up of 25.7 months (range: 3-48 months), all the eyes except one (91%, 10/11) demonstrated anatomical and functional success. CONCLUSION: Lacrimal drainage involvement was more common in Peters plus syndrome. Multiple proximal and distal lacrimal drainage segment anomalies were noted in all the variants of Peters anomaly; however, Peters plus syndrome was noted to usually involve both the segments.

Results of endoscopic endonasal dacryocystorhinostomy: A prospective cohort study.

OBJECTIVE: To evaluate the success rate of endoscopic endonasal dacryocystorhinostomy. METHODS: The prospective cohort study was conducted at the Ophthalmology and Otorhinolaryngology departments, Shifa Foundation Community Health Centre, Islamabad, Pakistan, from October 2017 to September 2019, and comprised chronic dacryocystitis patients who underwent endoscopic endonasal dacryocystorhinostomy. Endoscopic dacryocystorhinostomy with or without lacrimal intubation was performed under general anaesthesia. The patients were followed up post-operative at 1 week, 1 month, 6 months and 12 months. Data was analysed using SPSS 20. RESULTS: Of the 47 patients, 41(87.2%) were females. The overall mean age was 40.70±10.84 years (range: 25-66 years). Lacrimal intubation was performed in 31(66%) patients. Surgical success was achieved in 46(97.9%) patients. Of them, 37(78.7%) patients were completely symptom-free, while 9(19.1%) were partially symptomatic and were managed conservatively. Treatment failure requiring repeat surgical procedure was the case with 1(2.1%) patient. Procedure failure was more likely in patients with previous attacks of acute dacryocystitis (p=0.003). CONCLUSIONS: Endoscopic dacryocystorhinostomy was found to be a safe procedure with good anatomical and functional outcomes in chronic dacryocystitis patients.

Slow progressors to type 1 diabetes lose islet autoantibodies over time, have few islet antigen-specific CD8+ T cells and exhibit a distinct CD95hi B cell phenotype.

AIMS/HYPOTHESIS: The aim of this study was to characterise islet autoantibody profiles and immune cell phenotypes in slow progressors to type 1 diabetes. METHODS: Immunological variables were compared across peripheral blood samples obtained from slow progressors to type 1 diabetes, individuals with newly diagnosed or long-standing type 1 diabetes, and healthy individuals. Polychromatic flow cytometry was used to characterise the phenotypic attributes of B and T cells. Islet autoantigen-specific B cells were quantified using an enzyme-linked immunospot (ELISpot) assay and islet autoantigen-specific CD8+ T cells were quantified using peptide-HLA class I tetramers. Radioimmunoassays were used to detect islet autoantibodies. Sera were assayed for various chemokines, cytokines and soluble receptors via ELISAs. RESULTS: Islet autoantibodies were lost over time in slow progressors. Various B cell subsets expressed higher levels of CD95 in slow progressors, especially after polyclonal stimulation, compared with the corresponding B cell subsets in healthy donors (p < 0.05). The phenotypic characteristics of CD4+ and CD8+ T cells were similar in slow progressors and healthy donors. Lower frequencies of CD4+ T cells with a central memory phenotype (CD27int, CD127+, CD95int) were observed in slow progressors compared with healthy donors (mean percentage of total CD4+ T cells was 3.00% in slow progressors vs 4.67% in healthy donors, p < 0.05). Autoreactive B cell responses to proinsulin were detected at higher frequencies in slow progressors compared with healthy donors (median no. of spots was 0 in healthy donors vs 24.34 in slow progressors, p < 0.05) in an ELISpot assay. Islet autoantigen-specific CD8+ T cell responses were largely absent in slow progressors and healthy donors. Serum levels of DcR3, the decoy receptor for CD95L, were elevated in slow progressors compared with healthy donors (median was 1087 pg/ml in slow progressors vs 651 pg/ml in healthy donors, p = 0.06). CONCLUSIONS/INTERPRETATION: In this study, we found that slow progression to type 1 diabetes was associated with a loss of islet autoantibodies and a distinct B cell phenotype, consistent with enhanced apoptotic regulation of peripheral autoreactivity via CD95. These phenotypic changes warrant further studies in larger cohorts to determine their functional implications.

Outcomes of primary powered endoscopic dacryocystorhinostomy in syndromic congenital nasolacrimal duct obstruction.

Purpose: To evaluate the outcomes of powered endoscopic dacryocystorhinostomy (DCR) in syndromic individuals with congenital nasolacrimal duct obstruction (CNLDO).Methods: A retrospective multicenter case series of patients who required a primary powered endoscopic DCR for refractory CNLDO associated with syndromes or congenital craniofacial abnormalities was performed. A minimum follow-up of more than 6 months was considered for final analysis. Main outcome measures were anatomical and functional success at the last follow up.Results: Twenty primary powered endoscopic DCR's were performed in 12 patients (7 males, 5 females) with syndromic anomalies. The mean age at the time of surgery was 7.6 years (range: 2-22 years). The associated systemic anomalies were Down syndrome (42%, 5/12), ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome (17%, 2/12), gross craniofacial dysgenesis (25%, 3/12) Tessier cleft type 3 (8%, 1/12) and velocardiacfacial syndrome (8%, 1/12). Proximal system agenesis of the upper or lower canaliculus was present in 42% of patients (5 patients, 9 eyes). Adjunctive treatment in the form of Mitomycin C and/or intubation was performed in 55% (11/20) eyes. At a mean postoperative follow-up of 20 months, successful outcomes were noted in 95% of the eyes (19/20). The one eye with an anatomical failure was secondary to a complete cicatricial closure of the ostium and was successfully treated subsequently with a revision endoscopic DCR.Conclusion: Primary powered endoscopic DCR has good outcomes in patients with a CNLDO associated with craniofacial syndromes.

Use of Dermaflage®, a silicone-based skin camouflage product, for treatment of medial canthal fistula.

Medial canthal fistulas present a therapeutic challenge, given that the risk factors for development of this and similar complications also contribute to their difficulty to treat. Following surgical, chemotherapy and radiation treatment of a poorly differentiated sinonasal carcinoma, a 61 year old man failed internal and external rotational flap repair and declined further operative procedures; he was satisfied with a novel conservative treatment. This report describes use of Dermaflage®, a silicone-based skin camouflage and topical cutaneous filler product, to both resolve the symptoms of tearing and discharge through the fistula and mask the defect from the casual observer.