iGWAS: Image-based genome-wide association of self-supervised deep phenotyping of retina fundus images.

Existing imaging genetics studies have been mostly limited in scope by using imaging-derived phenotypes defined by human experts. Here, leveraging new breakthroughs in self-supervised deep representation learning, we propose a new approach, image-based genome-wide association study (iGWAS), for identifying genetic factors associated with phenotypes discovered from medical images using contrastive learning. Using retinal fundus photos, our model extracts a 128-dimensional vector representing features of the retina as phenotypes. After training the model on 40,000 images from the EyePACS dataset, we generated phenotypes from 130,329 images of 65,629 British White participants in the UK Biobank. We conducted GWAS on these phenotypes and identified 14 loci with genome-wide significance (p<5×10-8 and intersection of hits from left and right eyes). We also did GWAS on the retina color, the average color of the center region of the retinal fundus photos. The GWAS of retina colors identified 34 loci, 7 are overlapping with GWAS of raw image phenotype. Our results establish the feasibility of this new framework of genomic study based on self-supervised phenotyping of medical images.

Three-dimensional facial soft-tissue changes after surgical orthodontics in different vertical facial types of skeletal Class III malocclusion: A retrospective study.

The study compared the soft-tissue response to hard-tissue movement among different Class III vertical facial types after orthognathic surgery (OGS). The study included 90 consecutive adult patients with skeletal Class III malocclusion who underwent two-jaw OGS. Patients were divided into three groups (high, medium, and low angle) based on the presurgical Frankfort-mandibular plane angle. Cone-beam computerized tomographs were taken before surgery and after debonding. Soft- and hard-tissue linear and angular measurements were performed using three-dimensional reconstruction images. One-way analysis of variance was used for intergroup comparisons. Soft tissue tended to respond more to hard-tissue movement in the lower lip area in patients with low angle (mean = 0.089, SD = 0.047, p = 0.023), whereas no significant difference was observed for other sites. Consistently, L1/Li thickness increased most significantly in the high-angle group (mean = 1.98, SD = 2.14, p = 0.0001), and B/Si thickness decreased most significantly after surgery (mean = 2.16, SD = 2.68, p = 0.016). The findings suggest that the high-angle group had a higher chance of undergoing genioplasty to enhance chin contour. Different OGS plans should be considered for different Class III vertical facial types.

Acute cholangitis: Does malignant biliary obstruction vs choledocholithiasis etiology change the clinical presentation and outcomes?

BACKGROUND: Whether clinical outcomes of acute cholangitis (AC) vary by etiology is unclear. AIM: To compare outcomes in AC caused by malignant biliary obstruction (MBO) and common bile duct stones (CBDS). METHODS: This retrospective study included 516 patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) due to AC caused by MBO (MBO group, n = 56) and CBDS (CBDS group, n = 460). Clinical and laboratory parameters were compared between the groups. Propensity score matching (PSM) created 55 matched pairs. Confounders used in the PSM analysis were age, sex, time to ERCP, and technical success of ERCP. The primary outcome comparison was 30-d mortality. The secondary outcome comparisons were intensive care unit (ICU) admission rate, length of hospital stay (LOHS), and 30-d readmission rate. RESULTS: Compared with the CBDS group, the MBO group had significantly lower body temperature, percentage of abnormal white blood cell counts, and serum levels of aspartate aminotransferase, alanine aminotransferase, and creatinine. Body temperature, percent abnormal white blood cell count, and serum aspartate aminotransferase levels remained significantly lower in the MBO group in the PSM analysis. Platelet count, prothrombin time/international normalized ratio, and serum levels of alkaline phosphatase and total bilirubin were significantly higher in the MBO group. The MBO group had a significantly higher percentage of severe AC (33.9% vs 22.0%, P = 0.045) and received ERCP later (median, 92.5 h vs 47.4 h, P < 0.001). However, the two differences were not found in the PSM analysis. The 30-d mortality (5.4% vs 0.7%, P = 0.019), ICU admission rates (12.5% vs 4.8%, P = 0.028), 30-d readmission rates (23.2% vs 8.0%, P < 0.001), and LOHS (median, 16.5 d vs 7.0 d, P < 0.001) were significantly higher or longer in the MBO group. However, only LOHS remained significant in the PSM analysis. Multivariate analysis revealed that time to ERCP and multiple organ dysfunction were independent factors associated with 30-d mortality. CONCLUSION: MBO patients underwent ERCP later and thus had a worse prognosis than CBDS patients. Therefore, clinicians should remain vigilant in MBO patients with clinically suspected AC, and perform ERCP for biliary drainage as soon as possible.

The Impact of Metabolic Factors and Lipid-Lowering Drugs on Common Bile Duct Stone Recurrence after Endoscopic Sphincterotomy with Following Cholecystectomy.

BACKGROUND: Recurrent common bile duct stone after endoscopic retrograde cholangiopancreatography is an undesirable problem, even when a following cholecystectomy is carried out. Important factors are the composition and properties of stones; the most significant etiology among these is the lipid level. While numerous studies have established the association between serum lipid levels and gallstones, no study has previously reported on recurrent common bile duct stones after endoscopic sphincterotomy with following cholecystectomy. MATERIALS AND METHODS: We retrospectively collected 2016 patients underwent endoscopic sphincterotomy from 1 January 2015 to 31 December 2017 in Linkou Chang Gung Memorial Hospital. Finally, 303 patients whose serum lipid levels had been checked following a cholecystectomy after ERCP were included for analysis. We evaluated if metabolic factors including body weight, BMI, HbA1C, serum lipid profile, and lipid-lowering drugs may impact the rate of common bile duct stone recurrence. Furthermore, we tried to find if there is any factor that may impact time to recurrence. RESULTS: A serum HDL level ≥ 40 (p = 0.000, OR = 0.207, 95% CI = 0.114-0.376) is a protective factor, and a total cholesterol level ≥ 200 (p = 0.004, OR = 4.558, 95% CI = 1.625-12.787) is a risk factor of recurrent common bile duct stones after endoscopic sphincterotomy with cholecystectomy. Lipid-lowering drugs, specifically statins, have been shown to reduce the risk of recurrence significantly (p = 0.003, OR = 0.297, 95% CI = 0.132-0.665). No factors were found to impact the time to recurrence in this study. CONCLUSIONS: The serum lipid level could influence the recurrence of common bile duct stones after endoscopic sphincterotomy followed by cholecystectomy, and it appears that statins can reduce the risk of recurrence.

Dental Occlusion Characteristics for Treatment Decision-Making Regarding Surgery-First Approach in Orthodontics.

The surgery-first approach (SFA) is conducted to decrease the difficulty and duration of orthodontic treatment by correcting the skeletal discrepancy at the initial stage of treatment. However, the indication of the SFA has not been well defined yet. This study explored the dental occlusion characteristics for treatment decision-making regarding the SFA. A total of 200 skeletal Class III patients were consecutively collected and divided into two groups: the orthodontic-first approach (OFA) group and the SFA group. The pretreatment digital dental models and lateral cephalograms were measured. Logistic regression was completed and receiver operating characteristic (ROC) curves were obtained to predict the probability of the SFA. Results showed that the ROC model with L1-MP, upper and lower arch length discrepancy, overbite, and asymmetric tooth number as influencing factors revealed that the sensitivity and specificity for determining SFA were 83.0% and 65.0%, respectively; the accuracy of prediction was 75.0%. In conclusion, our findings indicate that the six measurements from digital dental models and lateral cephalograms can be effectively applied in treatment decision-making for the SFA with satisfactory accuracy.

Polymorphism at codon 31 of CDKN1A (p21) as a predictive factor for bevacizumab therapy in glioblastoma multiforme.

Glioblastoma (GBM), a prevalent and malignant brain tumor, poses a challenge in surgical resection due to its invasive nature within the brain parenchyma. CDKN1A (p21, Waf-1), a cyclin-dependent kinase inhibitor, plays a pivotal role in regulating cell growth arrest, terminal differentiation, and apoptosis. The existence of natural variants of CDKN1A has been associated with specific cancer types. In this retrospective study, our objective was to identify polymorphic variants of CDKN1A, specifically c.93C > A (codon 31 Ser31Arg), and investigate its potential impact within the scope of bevacizumab therapy for glioblastoma multiforme. This study involved a cohort of 139 unrelated adult Chinese GBM patients in Taiwan. Genomic DNA extracted from tumor samples was utilized for genotyping using the polymerase chain reaction (PCR) restriction fragment length polymorphism method (PCR-RFLP analysis). Through unconditional logistic regression analysis, odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. Our findings unveiled that among these GBM patients, the distribution of codon 31 polymorphisms was as follows: 23.02% were Serine homozygotes (Ser/Ser), 27.34% were Arginine homozygotes (Arg/Arg), and 49.64% were Serine/Arginine heterozygotes (Ser/Arg). While CDKN1A c.93C > A polymorphisms did not exhibit a direct association with overall survival in GBM patients, noteworthy survival benefits emerged among individuals with Arg/Arg and Arg/Ser genotypes who received combined concurrent chemoradiotherapy (CCRT) and bevacizumab treatment compared to those who underwent CCRT alone. Our findings indicate a significant involvement of the CDKN1A c.93C > A polymorphism in the development and onset of GBM, offering potential implications for the early prognostication of bevacizumab therapy outcomes.

Endoscopic Resection of Residual or Recurrent Lesions after Circumferential Radiofrequency Ablation for Flat Superficial Esophageal Squamous Cell Neoplasias.

The optimal treatment of residual/recurrent superficial esophageal squamous cell neoplasias (SESCNs) after circumferential radiofrequency (RFA) remains unclear. We aimed to report the efficacy and safety of endoscopic resection (ER) of residual/recurrent SESCNs after RFA. Patients who underwent circumferential RFA with residual/recurrent SESCNs and were treated with ER were retrospectively collected. SESCN patients treated with primary endoscopic submucosal dissection (ESD) served as the control group. Eleven patients who underwent RFA had a total of 17 residual (n = 8) or recurrent (n = 9) SESCNs and were treated for ER. EMR failed to remove one residual SESCN. Of the 16 resected specimens, 10 were high-grade intraepithelial neoplasia (HGIN) and six were cancer. Eight cases had neoplasia extending to esophageal ducts/submucosal glands (SMGs). The pathological results may imply three possible routes in which residual/recurrent SESCNs occurred: HGIN without ductal/SMG involvement (37.5%), HGIN with ductal/SMG involvement (25.0%), and SCC with muscularis mucosae or deeper involvement (37.5%). Compared with the control group, the study group had similar procedural speed, en bloc resection rate, R0 resection rate, and complication rate. In conclusion, the safety and efficacy of post-RFA ESD were similar to those of primary ESD. ESD should be the treatment of choice for residual/recurrent SESCNs after initial RFA.

Evaluation of pharyngeal airway space after orthodontic extraction treatment in class II malocclusion integrating with the subjective sleep quality assessment.

Orthodontic treatment with premolar extractions is typically used to relieve dental crowding and retract anterior teeth for lip profile improvement. The aim of the study is to compare the changes in regional pharyngeal airway space (PAS) after orthodontic treatment with Class II malocclusion and to identify the correlations between questionnaire results and PAS dimensions after orthodontic treatment. In this retrospective cohort study, 79 consecutive patients were divided into normodivergent nonextraction, normodivergent extraction, and hyperdivergent extraction groups. Serial lateral cephalograms were used to evaluate the patients' PASs and hyoid bone positions. The Pittsburgh Sleep Quality Index and STOP-Bang questionnaire were used for sleep quality evaluation and obstructive sleep apnea (OSA) risk assessment, respectively, after treatment. The greatest airway reduction was observed in hyperdivergent extraction group. However, the changes in PAS and hyoid positions did not differ significantly among three groups. According to questionnaire results, all three groups had high sleep quality and low risk of OSA, with no significant intergroup differences. Moreover, pretreatment-to-posttreatment changes in PAS were not correlated with sleep quality or risk of OSA. Orthodontic retraction with premolar extractions nither exhibit significant reduction in airway dimensions nor increase their risk of OSA.

Mettl14-mediated m6A modification ensures the cell-cycle progression of late-born retinal progenitor cells.

Neural progenitor cells lengthen their cell cycle to prime themselves for differentiation as development proceeds. It is currently not clear how they counter this lengthening and avoid being halted in the cell cycle. We show that N6-methyladenosine (m6A) methylation of cell-cycle-related mRNAs ensures the proper cell-cycle progression of late-born retinal progenitor cells (RPCs), which are born toward the end of retinogenesis and have long cell-cycle length. Conditional deletion of Mettl14, which is required for depositing m6A, led to delayed cell-cycle exit of late-born RPCs but has no effect on retinal development prior to birth. m6A sequencing and single-cell transcriptomics revealed that mRNAs involved in elongating the cell cycle were highly enriched for m6A, which could target them for degradation and guarantee proper cell-cycle progression. In addition, we identified Zfp292 as a target of m6A and potent inhibitor of RPC cell-cycle progression.

Intraductal papillary neoplasm of the bile duct presenting with hepatogastric fistula: a case report and literature review.

Intraductal papillary neoplasm of the bile duct (IPNB) is an uncommon entity characterized by papillary growth within the bile duct lumen. IPNB is regarded as a biliary counterpart of intraductal papillary mucinous neoplasm of the pancreas, which sometimes complicates with fistula formation to adjacent organs, mainly due to high-pressure related erosion from mucin-filled ducts. However, fistula formation from IPNB is quite rare. Here we report a case of IPNB complicated with hepatogastric fistula. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) revealed disproportional dilatation of left intrahepatic duct with intraluminal soft tissue nodules and fistulous connections to gastric high body. Endoscopy revealed ulcers with two fistulous orifices at upper gastric body. The patient underwent left hepatectomy with gastric wedge resection. Histopathology examination revealed IPNB with invasive cholangiocarcinoma, directly invading to gastric wall leading to hepatogastric fistula. In summary, we have presented the clinical, imaging and pathological findings, along with a comprehensive review of relevant literature, in order to enhance the understanding of this rare condition.

Efficacy of Fully Covered Self-Expandable Metal Stents for Distal Biliary Obstruction Caused by Pancreatic Ductal Adenocarcinoma: Primary Metal Stent vs. Metal Stent following Plastic Stent.

Fully covered self-expandable metallic stents (FCSEMSs) are inserted in patients with unresectable pancreatic ductal adenocarcinoma (PDAC) to resolve malignant distal bile duct obstructions. Some patients receive FCSEMSs during primary endoscopic retrograde cholangiopancreatography (ERCP), and others receive FCSEMSs during a later session, after the placement of a plastic stent. We aimed to evaluate the efficacy of FCSEMSs for primary use or following plastic stent placement. A total of 159 patients with pancreatic adenocarcinoma (m:f, 102:57) who had achieved clinical success underwent ERCP with the placement of FCSEMSs for palliation of obstructive jaundice. One-hundred and three patients had received FCSEMSs in a first ERCP, and 56 had received FCSEMSs after prior plastic stenting. Twenty-two patients in the primary metal stent group and 18 in the prior plastic stent group had recurrent biliary obstruction (RBO). The RBO rates and self-expandable metal stent patency duration did not differ between the two groups. An FCSEMS longer than 6 cm was identified as a risk factor for RBO in patients with PDAC. Thus, choosing an appropriate FCSEMS length is an important factor in preventing FCSEMS dysfunction in patients with PDAC with malignant distal bile-duct obstruction.

Surgical Stability After Proximal Segment Angle Alteration in Patients With Class III Facial Asymmetry.

PURPOSE: Patients with facial asymmetry often seek improved symmetry in lower face contour resulting in transverse movement of the proximal segments. The study aimed to investigate the association between transverse change in the proximal segments and postoperative relapse after the surgical correction of skeletal Class III facial asymmetry. METHODS: This retrospective cohort study includes consecutive patients with skeletal Class III asymmetry who underwent 2-jaw orthognathic surgery. The primary predictor variable was ramus plane angle (RPA). The patients were grouped as small (S group, <4°) and large (L group, ≥4°) changes in RPA. The primary outcome was the positional change of B point, menton, and the intergonial width. Cone-beam computed tomography images were obtained before surgery (T0), 1 week after surgery (T1), and debond (T2). Intergroup comparison was conducted with independent t test. Correlations between the variables were estimated by Pearson correlation. RESULTS: The study sample was composed of 60 subjects with 30 subjects in each study group. In the S group, the mean surgical changes of RPA were inward rotated 0.91° bilaterally. In the L group, the mean surgical changes of RPA were inward rotated 4.80° and 0.32° on the deviated and non-deviated side. After surgery, further minor inward adaptation of both sides was noted (<1 mm), and intergonial distance reduced with these changes in the proximal segments. By comparing the postsurgical stability between S and L group, the overall sagittal and vertical stability had no significant difference between 2 groups. However, the postsurgical transverse menton relapse (ΔMe in T2-T1) was significantly larger in L group (0.81 ± 1.40 mm) than S group (0.04 ± 1.32 mm) by 0.77 mm (P = .014). CONCLUSION: Greater surgical changes in the proximal segments had minor clinical effect on transverse stability. Minor transverse overcorrection of 1 mm is recommended in cases with severe facial symmetry with extensive changes in the proximal segments.

Timing of endoscopic retrograde cholangiopancreatography in the treatment of acute cholangitis of different severity.

BACKGROUND: The optimal timing of endoscopic retrograde cholangiopancreatography (ERCP) in acute cholangitis (AC) is uncertain, especially in patients with AC of varying severity. AIM: To report whether the timing of ERCP is associated with outcomes in AC patients with different severities. METHODS: According to the 2018 Tokyo guidelines, 683 patients who met the definite diagnostic criteria for AC were retrospectively identified. The results were first compared between patients receiving ERCP ≤ 24 h and > 24 h and then between patients receiving ERCP ≤ 48 h and > 48 h. Subgroup analyses were performed in patients with grade I, II or III AC. The primary outcome was 30-d mortality. Secondary outcomes were intensive care unit (ICU) admission rate, length of hospital stay (LOHS) and 30-d readmission rate. RESULTS: Taking 24 h as the critical value, compared with ERCP > 24 h, malignant biliary obstruction as a cause of AC was significantly less common in the ERCP ≤ 24 h group (5.2% vs 11.5%). The proportion of cardiovascular dysfunction (11.2% vs 2.6%), respiratory dysfunction (14.2% vs 5.3%), and ICU admission (11.2% vs 4%) in the ERCP ≤ 24 h group was significantly higher, while the LOHS was significantly shorter (median, 6 d vs 7 d). Stratified by the severity of AC, higher ICU admission was only observed in grade III AC and shorter LOHS was only observed in grade I and II AC. There were no significant differences in 30-d mortality between groups, either in the overall population or in patients with grade I, II or III AC. With 48 h as the critical value, compared with ERCP > 48 h, the proportion of choledocholithiasis as the cause of AC was significantly higher in the ERCP ≤ 48 h group (81.5% vs 68.3%). The ERCP ≤ 48 h group had significantly lower 30-d mortality (0 vs 1.9%) and shorter LOHS (6 d vs 8 d). Stratified by AC severity, lower 30-d mortality (0 vs 6.1%) and higher ICU admission rates (22.2% vs 10.2%) were only observed in grade III AC, and shorter LOHS was only observed in grade I and II AC. In the multivariate analysis, cardiovascular dysfunction and time to ERCP were two independent factors associated with 30-d mortality. CONCLUSION: ERCP ≤ 48 h conferred a survival benefit in patients with grade III AC. Early ERCP shortened the LOHS in patients with grade I and II AC.

Endoscopic salvage therapy after failed biliary cannulation using advanced techniques: A concise review.

Therapeutic endoscopic retrograde cholangiopancreatography (ERCP) begins with successful biliary cannulation. However, it is not always be successful. The failure of the initial ERCP is attributed to two main aspects: the papilla/biliary orifice is endoscopically accessible, or it is inaccessible. When the papilla/biliary orifice is accessible, bile duct cannulation failure can occur even with advanced cannulation techniques, including double guidewire techniques, transpancreatic sphincterotomy, needle-knife precut papillotomy, or fistulotomy. There is currently no consensus on the next steps of treatment in this setting. Therefore, this review aims to propose and discuss potential endoscopic options for patients who have failed ERCP due to difficult bile duct cannulation. These options include interval ERCP, percutaneous-transhepatic-endoscopic rendezvous procedures (PTE-RV), and endoscopic ultrasound-assisted rendezvous procedures (EUS-RV). The overall success rate for interval ERCP was 76.3% (68%-79% between studies), and the overall adverse event rate was 7.5% (0-15.9% between studies). The overall success rate for PTE-RV was 88.7% (80.4%-100% between studies), and the overall adverse event rate was 13.2% (4.9%-19.2% between studies). For EUS-RV, the overall success rate was 82%-86.1%, and the overall adverse event rate was 13%-15.6%. Because interval ERCP has an acceptably high success rate and lower adverse event rate and does not require additional expertise, facilities, or other specialists, it can be considered the first choice for salvage therapy. EUS-RV can also be considered if local experts are available. For patients in urgent need of biliary drainage, PTE-RV should be considered.

Sequential digital occlusal analysis in patients with skeletal Class III malocclusion with orthognathic surgery: Surgery-first vs orthodontic-first approach.

INTRODUCTION: This study compared changes in occlusal characteristics in patients with skeletal Class III malocclusion with surgery-first approach (SFA) and those with orthodontic-first approach (OFA) through digital occlusal analysis. METHODS: In this prospective study, 90 consecutive subjects were divided into control, OFA, and SFA groups (30 per group). Force discrepancy, occlusal time, tooth contact, center of force, and force-time graph pattern were calculated for all samples using the T-Scan III system. Between-group differences were analyzed using a 1-way analysis of variance and generalized estimating equations. These parameters were calculated at the following time points: preoperatively, 1-month postoperatively (T1), 4-months postoperatively, and 1-year postoperatively (T3). RESULTS: No significant differences were observed in the parameters between the experimental groups. The force discrepancy of the OFA and SFA groups decreased, approaching the value of controls at T3. The occlusal time significantly increased at T1 and progressively decreased at T3. The initial contact and maximum force were most frequently observed on molars, and its maximum force significantly decreased by 5.72% and 7.40% in the OFA and SFA groups at T3, respectively. The number of tooth contact was significantly reduced at T1 and gradually increased at T3. Moreover, after surgery, the force-time graph pattern was normalized, and the center of force tended to be more centric; however, the most frequent trajectory revealed premature contact during closing. CONCLUSIONS: No significant difference was found in all parameters between the OFA and SFA groups. Occlusion deteriorated at 1 month postoperatively but gradually improved at 1 year postoperatively, approaching the controls.

Craniofacial Morphologic Predictors for Passive Myofunctional Therapy of Pediatric Obstructive Sleep Apnea Using an Oral Appliance with a Tongue Bead.

We conducted this retrospective study to identify potential clinical, polysomnographic, and cephalometric predictors for the treatment outcomes of a tongue-beaded oral appliance (OA) in children with obstructive sleep apnea syndrome (OSAS). In total, 63 patients­50 boys and 13 girls ranging in age from 4 to 16 years­underwent OA treatment nightly for at least 6 months. A baseline digital lateral cephalometric radiograph was obtained for each patient. Multivariate logistic regression analysis was performed to examine predictors for the treatment outcome based on the clinical and cephalometric measurements. Overall, 28 patients responded to the treatment (post-treatment improvement > 50% or apnea−hypopnea index (AHI) < 1/h), and 35 did not (post-treatment improvement < 50% and AHI ≥ 1/h). Significantly larger cranial base angle (SNBa), smaller lower gonial angle (LGo Angle), and shorter length of anterior cranial base (SN) were found in responders. Smaller lower gonial angle (LGo Angle) and smaller anterior cranial base (SN) predict a favorable outcome for pediatric OSAS using a tongue-beaded OA. This finding will equip practitioners with additional insights when selecting suitable candidates for OA therapy in pediatric patients.

Predictive factors of needle-knife pre-cut papillotomy failure in patients with difficult biliary cannulation.

Predictors of needle-knife pre-cut papillotomy (NKP) failure for patients with difficult biliary cannulation has not been reported. Between 2004 and 2016, 390 patients with difficult biliary cannulation undergoing NKP were included in this single-center study. Following NKP, deep biliary cannulation failed in 95 patients (24.4%, NKP-failure group) and succeeded in 295 patients (75.6%, NKP-success group). Patient and technique factors were used to identify the predictors of initial NKP failure. Compared with the NKP-success group, periampullary diverticulum (28.4% vs. 18%, p = 0.028), surgically altered anatomy (13.7% vs. 7.1%, p = 0.049), number of cases performed by less experienced endoscopists, and bleeding during NKP (38.9% vs. 3.4%, p < 0.001), were significantly more frequent in the NKP-failure group. On multivariate analysis, surgically altered anatomy (OR 2.374, p = 0.045), endoscopists' experience (OR 3.593, p = 0.001), and bleeding during NKP (OR 21.18, p < 0.001) were significantly associated with initial failure of NKP. In conclusion, NKP is a highly technique-sensitive procedure, as endoscopists' experience, bleeding during NKP, and surgically altered anatomy were predictors of initial NKP failure.

A protocol to inject ocular drug implants into mouse eyes.

Ocular drug implants (ODIs) are beneficial for treating ocular diseases. However, the lack of a robust injection approach for small-eyed model organisms has been a major technical limitation in developing ODIs. Here, we present a cost-effective, minimally invasive protocol to deliver ODIs into the mouse vitreous called Mouse Implant Intravitreal Injection (MI3). MI3 provides two alternative surgical approaches (air-pressure or plunger) to deliver micro-scaled ODIs into milli-scaled eyes, and expands the preclinical platforms to determine ODIs' efficacy, toxicity, and pharmacokinetics. For complete details on the use and execution of this protocol, please refer to Sun et al. (2021).