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.

Identification of cis-regulatory modules for adeno-associated virus-based cell-type-specific targeting in the retina and brain.

Adeno-associated viruses (AAVs) targeting specific cell types are powerful tools for studying distinct cell types in the central nervous system (CNS). Cis-regulatory modules (CRMs), e.g., enhancers, are highly cell-type-specific and can be integrated into AAVs to render cell type specificity. Chromatin accessibility has been commonly used to nominate CRMs, which have then been incorporated into AAVs and tested for cell type specificity in the CNS. However, chromatin accessibility data alone cannot accurately annotate active CRMs, as many chromatin-accessible CRMs are not active and fail to drive gene expression in vivo. Using available large-scale datasets on chromatin accessibility, such as those published by the ENCODE project, here we explored strategies to increase efficiency in identifying active CRMs for AAV-based cell-type-specific labeling and manipulation. We found that prescreening of chromatin-accessible putative CRMs based on the density of cell-type-specific transcription factor binding sites (TFBSs) can significantly increase efficiency in identifying active CRMs. In addition, generation of synthetic CRMs by stitching chromatin-accessible regions flanking cell-type-specific genes can render cell type specificity in many cases. Using these straightforward strategies, we generated AAVs that can target the extensively studied interneuron and glial cell types in the retina and brain. Both strategies utilize available genomic datasets and can be employed to generate AAVs targeting specific cell types in CNS without conducting comprehensive screening and sequencing experiments, making a step forward in cell-type-specific research.

Cell type- and stage-specific expression of Otx2 is regulated by multiple transcription factors and cis-regulatory modules in the retina.

Transcription factors (TFs) are often used repeatedly during development and homeostasis to control distinct processes in the same and/or different cellular contexts. Considering the limited number of TFs in the genome and the tremendous number of events that need to be regulated, re-use of TFs is necessary. We analyzed how the expression of the homeobox TF, orthodenticle homeobox 2 (Otx2), is regulated in a cell type- and stage-specific manner during development in the mouse retina. We identified seven Otx2 cis-regulatory modules (CRMs), among which the O5, O7 and O9 CRMs mark three distinct cellular contexts of Otx2 expression. We discovered that Otx2, Crx and Sox2, which are well-known TFs regulating retinal development, bind to and activate the O5, O7 or O9 CRMs, respectively. The chromatin status of these three CRMs was found to be distinct in vivo in different retinal cell types and at different stages. We conclude that retinal cells use a cohort of TFs with different expression patterns and multiple CRMs with different chromatin configurations to regulate the expression of Otx2 precisely.

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.

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.

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.

The influence of a GT repeat polymorphism on poly(I:C) induction of the grouper MxII gene promoter in GK cells.

Interferons play an important role in the fish innate immune system against viral infection by inducing the interferon stimulated genes, such as Mx gene. We cloned the MxII gene promoter from orange-spotted grouper and found three MxII gene promoters. All of them contained two interferon stimulated response elements (ISREs), and three dinucleotide repeat sequences located at 5' end of ISREs. Interestingly, there is a polymorphic GT repeat element located upstream of these ISREs. The three MxII gene promoters respectively contained 27, 29, and 31 GT repeats, namely EcMx_27, EcMx_29, and EcMx_31. To determine whether GT repeat element influence the MxII gene expression, the MxII gene promoters were subcloned into promoterless reporter plasmid and transfected into grouper kidney (GK) cells. The results showed that a significant induction by poly(I:C) was detected in GK cells transfected with pEcMx_31 (2.65 folds) whereas there was no induction in GK cells transfected with pEcMx_27 and pEcMx_29. However, the significant induction by nervous necrosis virus (NNV) infection was found in GK cells separately transfected with three reporter plasmids. These results suggest that the GT repeat element plays an important role in modulation of MxII gene expression and the induction by poly(I:C) and NNV may be mediated through different signal transduction pathways.

Risk of Renal Injury After the Use of Polyethylene Glycol for Outpatient Colonoscopy: A Prospective Observational Study.

GOAL: The goal of this study was to estimate the risk of renal injury after the use of 3-L polyethylene glycol (PEG) before outpatient colonoscopy. BACKGROUND: Population-based studies showed that the use of PEG was associated with renal injury, but this association has not been confirmed by prospective study. STUDY: Patients ≥40 years of age with an estimated glomerular filtration rate ≥30 mL/min were screened for enrollment. Laboratory data were collected before, during, and after the colonoscopies. Patients with a ≥30% increase in baseline serum creatinine levels were followed until a peak level was detected. Renal injury included acute renal dysfunction (ARD) and acute kidney injury (AKI), defined as a 30% to 49% increase and ≥50% increase in creatinine levels compared with the baseline, respectively. RESULTS: A total of 1163 patients (mean age, 55.7 y) completed the study. Baseline and first postcolonoscopy laboratory data were obtained an average of 17.0 days before and 17.3 days after the colonoscopies were performed, respectively. Renal injury was identified in 32 patients; 26 patients (2.2%) had ARD, and 6 patients (0.5%) had AKI. All patients with renal injury recovered fully during follow-up. In the subgroup analysis, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) before colonoscopy was statistically associated with the development of AKI (odds ratio, 6.5; 95% confidence interval, 1.2-35.5; P=0.03). CONCLUSIONS: This prospective study showed that the use of PEG was associated with a small risk of renal injury. NSAIDs use was statistically associated with AKI in the context of colonoscopy for which PEG was used for bowel preparation.

Comparison of polyp detection during both insertion and withdrawal versus only withdrawal of colonoscopy: A prospective randomized trial.

BACKGROUND AND AIMS: Polyps seen and not removed during colonoscope insertion are sometimes unable to be found during withdrawal. We aimed to evaluate whether additional inspection and polypectomy during insertion increases adenoma detection rate (ADR) compared with inspection and polypectomy entirely during withdrawal. METHODS: A total of 421 patients aged ≥ 45 years and undergoing colonoscopy were prospectively randomized to receive inspection and polypectomy during both insertion and withdrawal (study group) or inspection and polypectomy entirely during withdrawal (control group). The primary outcome was the ADR. Secondary outcomes included other adenoma-related parameters and procedure-related measures. RESULTS: Baseline demographics, procedure indications, preparation quality, total procedure time, sedative doses, colonoscopy difficulty, and patient discomfort were similar between the groups. The insertion time was significantly longer in the study group (11.1 ± 4.8 vs 6.2 ± 4.7 min, P < 0.0001). The withdrawal time was significantly longer in the control group (29.2 ± 9.8 vs 23.1 ± 7.9 min, P < 0.0001). There was no significant difference in the ADR (63.5% [study group] vs 68.1% [control group]), the mean adenoma per procedure (1.6 ± 2.0 vs 1.9 ± 2.4), or the mean adenoma per positive procedure (2.5 ± 2.0 vs 2.7 ± 2.5) between groups. The proximal colon ADR was significantly higher in the control group compared with the study group (56.2% vs 46.0%, P = 0.041). CONCLUSIONS: Additional inspection and polypectomy during colonoscope insertion did not improve ADR compared with inspection and polypectomy entirely during withdrawal. These results do not support an additional role for routine inspection during insertion (clinical trial registration number: NCT03444090).

The Immune Activity of PT-Peptide Derived from Anti-Lipopolysaccharide Factor of the Swimming Crab Portunus trituberculatus Is Enhanced when Encapsulated in Milk-Derived Extracellular Vesicles.

PT-peptide is derived from the anti-lipopolysaccharide factor of the swimming crab Portunus trituberculatus. The peptide, consisting of 34 amino acids, contains a lipopolysaccharide binding domain. In this study, we investigated the effect of PT-peptide encapsulated in raw milk-derived extracellular vesicles (EVs), designated as EVs-PT peptide, on immune regulation. The results showed that raw milk-derived EVs efficaciously delivered the PT-peptide into monocytes and elevated immune activity, including reactive oxygen species level, superoxide anion production, and phagocytosis. PT-peptide and EVs-PT peptide also elevated the secretion of cytokines, such as interferon-γ, interleukin-6, and tumor necrosis factor-α in human monocytic THP-1 cells. These results suggest that the PT-peptide could be developed as an immune stimulator.

Low-Luminance Blue Light-Enhanced Phototoxicity in A2E-Laden RPE Cell Cultures and Rats.

N-retinylidene-N-retinylethanolamine (A2E) and other bisretinoids are components of lipofuscin and accumulate in retinal pigment epithelial (RPE) cells-these adducts are recognized in the pathogenesis of retinal degeneration. Further, blue light-emitting diode (LED) light (BLL)-induced retinal toxicity plays an important role in retinal degeneration. Here, we demonstrate that low-luminance BLL enhances phototoxicity in A2E-laden RPE cells and rats. RPE cells were subjected to synthetic A2E, and the effects of BLL on activation of apoptotic biomarkers were examined by measuring the levels of cleaved caspase-3. BLL modulates the protein expression of zonula-occludens 1 (ZO-1) and paracellular permeability in A2E-laden RPE cells. Early inflammatory and angiogenic genes were also screened after short-term BLL exposure. In this study, we developed a rat model for A2E treatment with or without BLL exposure for 21 days. BLL exposure caused fundus damage, decreased total retinal thickness, and caused neuron transduction injury in the retina, which were consistent with the in vitro data. We suggest that the synergistic effects of BLL and A2E accumulation in the retina increase the risk of retinal degeneration. These outcomes help elucidate the associations between BLL/A2E and angiogenic/apoptotic mechanisms, as well as furthering therapeutic strategies.

Novel Protective Effects of Cistanche Tubulosa Extract Against Low-Luminance Blue Light-Induced Degenerative Retinopathy.

BACKGROUND/AIMS: Blue light-emitting diode light (BLL)-induced phototoxicity plays an important role in ocular diseases and causes retinal degeneration and apoptosis in human retinal pigment epithelial (RPE) cells. Cistanche tubulosa extract (CTE) is a traditional Chinese medicine with many beneficial protective properties; however, few studies have examined the ocular protective roles of CTE. In this study, we investigated the mechanisms underlying the effects of CTE on BLL-induced apoptosis in vitro and in vivo. METHODS: RPE cells were applied in the current in vitro study and cell viability was determined by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis-related protein expression was determined by western blot analysis and immunofluorescence staining. Brown Norway rats were used to examine exposure to commercially available BLL in vivo. Hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and western blot assays were used to examine retinal morphological deformation. RESULTS: CTE significantly inhibited hydrogen peroxide-, tert-butyl hydroperoxide-, sodium azide-, and BLL-induced RPE damage. Further, CTE reduced the expression of apoptotic markers such as cleaved caspase-3 and TUNEL staining after BLL exposure by inactivating apoptotic pathways, as shown via immunofluorescent staining. In addition, CTE inhibited the BLL-induced phosphorylation of c-Jun N-terminal kinase, extra signal-related kinases 1/2, and p38 in RPE cells. In vivo, the oral administration of CTE rescued 60-day periodic BLL exposure-induced decrements in retinal thickness and reduced the number of TUNEL-positive cells in the brown Norway rat model. CONCLUSION: CTE is a potential prophylactic agent against BLL-induced phototoxicity.

Multiple sleep latency test in narcolepsy type 1 and narcolepsy type 2: A 5-year follow-up study.

Excessively sleepy teenagers and young adults without sleep-disordered breathing are diagnosed with either narcolepsy type 1 or narcolepsy type 2, or hypersomnia, based on the presence/absence of cataplexy and the results of a multiple sleep latency test. However, there is controversy surrounding this nomenclature. We will try to find the differences between different diagnoses of hypersomnia from the results of the long-term follow-up evaluation of a sleep study. We diagnosed teenagers who had developed excessive daytime sleepiness based on the criteria of the International Classification of Sleep Disorders, 3rd edition. Each individual received the same clinical neurophysiologic testing every year for 5 years after the initial diagnosis of narcolepsy type 1 (n = 111) or type 2 (n = 46). The follow-up evaluation demonstrated that narcolepsy type 1 (narcolepsy-cataplexy) is a well-defined clinical entity, with very reproducible clinical neurophysiologic findings over time, whereas patients with narcolepsy type 2 presented clear clinical and test variability. By the fifth year of the follow-up evaluation, 17.6% of subjects did not meet the diagnostic criteria of narcolepsy type 2, and 23.9% didn't show any two sleep-onset rapid eye movement periods in multiple sleep latency during the 5-year follow-up. Therefore narcolepsy type 1 (narcolepsy-cataplexy) is a well-defined syndrome, with the presentation clearly related to the known consequences of destruction of hypocretin/orexin neurons. Narcolepsy type 2 covers patients with clinical and test variability over time, thus bringing into question the usage of the term "narcolepsy" to label these patients.

Optimal procedural sequence for same-day bidirectional endoscopy with moderate sedation: A prospective randomized study.

BACKGROUND AND AIM: Same-day bidirectional endoscopy (BDE) is a commonly performed procedure, but the optimal sequence for the procedure with moderate conscious sedation is not well established. This study investigated the optimal sequence for same-day BDE under moderate conscious sedation and carbon dioxide insufflation in terms of sedation doses, patient discomfort, and colonoscopy performance. METHODS: A prospective randomized controlled study of 120 patients who were scheduled for BDE examination was performed. Colonoscopy followed by esophagogastroduodenoscopy (EGD) examination was performed in 60 patients (colonoscopy-EGD group), and EGD followed by colonoscopy examination was performed in another 60 patients (EGD-colonoscopy group). Endoscopists and patients completed a questionnaire to assess objective and subjective discomfort. RESULTS: Baseline demographics, procedure indications, bowel preparation quality, cecal intubation rate/time, colonoscopy withdrawal time, endoscopic interventions, BDE procedure time, colon polyp/adenoma detection rates, patient discomfort, and adverse events were similar between the two study groups. The total doses of fentanyl and midazolam were significantly higher for the colonoscopy-EGD group than for the EGD-colonoscopy group (83.4 ± 17.7 vs 68.7 ± 18.6 µg and 6.3 ± 1.4 vs 5.2 ± 1.3 mg, P < 0.0001 and P < 0.0001, respectively). The recovery time to discharge was significantly longer for the colonoscopy-EGD group than for the EGD-colonoscopy group (43.5 ± 16.2 vs 34.5 ± 8.9 min, P = 0.0003). CONCLUSIONS: Esophagogastroduodenoscopy followed by colonoscopy is the optimal sequence for same-day BDE under moderate conscious sedation and carbon dioxide insufflation. Following this order allows for a reduction of sedation doses and for shorter recovery times.

Enhanced Surgical Outcomes in Patients With Skeletal Class III Facial Asymmetry by 3-Dimensional Surgical Simulation.

PURPOSE: With the advance of image fusion techniques, the creation of 3-dimensional (3D) virtual head and 3D surgical simulations has provided previews of surgical procedures. The aim of this study was to investigate the surgical outcomes in patients receiving orthognathic surgery (OGS) with the guidance of 3D computer-assisted surgical simulation. PATIENTS AND METHODS: The study included 34 consecutive patients (15 men and 19 women; age, 18.1 to 33.0 yr) with skeletal Class III facial asymmetry who underwent bimaxillary OGS. One-week postoperative cone-beam computed tomographic craniofacial images (Ta) were constructed and superimposed on preoperative simulated virtual images (Ts) at the cranial base and surfaces of the frontal and periorbital regions. The 3D cephalometric landmarks were measured relative to 3 reference planes. The outcomes among different experience levels of surgeons also were compared. RESULTS: Although the mean values between Ta and Ts were small, statistical differences were observed in the center of maxillary and mandibular incisors and the B point relative to the midline and in the maxillary first molar in vertical distances, sagittal dentoskeletal dimensions, and pitch angles. The root mean square deviations (RMSDL) of measurement variables relative to center landmark accuracy were 1.5 and less than 2 mm at the maxilla and mandible, respectively. RMSDL greater than 2 mm was located at the maxillary first molar in the vertical distance and in the sagittal dimension at the anterior nasal spine and B point. Variables related to centering the midline structures were highly inter-related. The roll angle deviation was associated with centering the midline landmarks. The yaw angle deviation was not associated with midline correction. CONCLUSION: With guidance from 3D surgical simulation, surgeons could achieve similar outcomes to correct facial asymmetry regardless of their years of practice.

Residual Gastric Volume After Bowel Preparation With Polyethylene Glycol for Elective Colonoscopy: A Prospective Observational Study.

GOAL: To examine the residual gastric volume (RGV) in colonoscopy after bowel preparations with 3-L polyethylene glycol (PEG). BACKGROUND: Obstacles to high-volume bowel preparation by anesthesia providers resulting from concerns over aspiration risk are common during colonoscopy. STUDY: Prospective measurements of RGV were performed in patients undergoing esophagogastroduodenoscopy (EGD) and morning colonoscopy with split-dose PEG preparation, patients undergoing EGD and afternoon colonoscopy with same-day PEG preparation, and patients undergoing EGD alone under moderate conscious sedation. Colonoscopy patients were allowed to ingest clear liquids until 2 hours before the procedure. Patients undergoing EGD alone were instructed to eat/drink nothing after midnight. RESULTS: There were 860 evaluated patients, including 330 in the split-dose preparation group, 100 in the same-day preparation group, and 430 in the EGD-only group. Baseline demographics and disease/medication factors were similar. The mean RGV in patients receiving the same-day preparation (35.4 mL or 0.56 mL/kg) was significantly higher than that in patients receiving the split-dose preparation (28.5 mL or 0.45 mL/kg) and in patients undergoing EGD alone (22.8 mL or 0.36 mL/kg) (P=0.023 and P<0.0001, respectively). Within the bowel-preparation groups, patients with fasting times of 2 to 3 hours had similar RGV compared with patients who had fasting times >3 hours. The shape of the distribution and the range of RGV among the 3 study groups were similar. No aspiration occurred in any group. CONCLUSIONS: PEG bowel preparations increase RGV mildly, but seem to have no clinical significance. These results support the current fasting guidelines for colonoscopy.

Predictors of Suboptimal Bowel Preparation Using 3-l of Polyethylene Glycol for an Outpatient Colonoscopy: A Prospective Observational Study.

BACKGROUND: A 3-l polyethylene glycol (PEG) solution provided better bowel cleansing quality than a 2-l solution for outpatient colonoscopy. Predictors of suboptimal preparation using a 3-l PEG have not been previously reported. AIMS: To investigate the possible predictors of suboptimal bowel preparation using 3-l of PEG. METHODS: We analyzed a database of 1404 consecutive colonoscopies during a 27-month period at a community hospital. A split-dose PEG regimen was provided for morning colonoscopies, and a same-day PEG regimen was provided for afternoon colonoscopies. The level of bowel cleansing was prospectively scored according to the Boston Bowel Preparation Scale (BBPS). Possible predictors of suboptimal colon preparation, defined as a BBPS score <7, were analyzed using univariate statistics and multivariate logistic regression models. RESULTS: The mean age of the study population (46.7 % men) was 52.5 years (range 20-80 years, SD 11.1 years), and the majority of patients (77.6 %) underwent morning colonoscopies. A suboptimal bowel preparation was reported in 17.2 % of the observed colonoscopies. In the multivariate regression analysis, constipation (odds ratio [OR] 1.60, 95 % confidence interval [CI] 1.15-2.22), male gender (OR 1.68, 95 % CI 1.25-2.25), obesity (OR 1.76, 95 % CI 1.29-2.41), and inadequate (<80 %) PEG consumption (OR 5.4, 95 % CI 2.67-10.89) were independent predictors of a suboptimal colon preparation. CONCLUSIONS: This prospective study identified that constipation, male gender, obesity, and inadequate intake of PEG were significant risk factors for suboptimal bowel preparation using a 3-l PEG solution for outpatient colonoscopy. Interventions of optimized colonoscopy preparation should be targeted at these patient populations.

Double-balloon enteroscopy-assisted endoscopic retrograde cholangiography for Roux-en-Y reconstruction patients with papilla of Vater or bilioenteric anastomosis.

OBJECTIVE: Roux-en-Y reconstructions can be divided into intact papilla of Vater and bilioenteric anastomosis (BEA) with respect to endoscopic retrograde cholangiography (ERC). Double-balloon enteroscopy-assisted ERC (DBE-ERC) may produce different results between the two populations but lacks studies. MATERIAL AND METHODS: Forty-seven patients with Roux-en-Y anastomosis undergoing 73 procedures of DBE-ERC were enrolled between July 2007 and August 2013. There were 14 patients with intact papilla of Vater (group A) and 33 patients with BEA (group B). The effectiveness of DBE-ERC, including data of reaching the blind end, performance of ERC, results of endoscopic therapies, and follow-up were retrospectively analyzed and compared between the two groups. RESULTS: For reaching the blind end, the success rate was not different between the groups (85.7% vs. 81.8%, p = 0.7), but the mean procedure time was significantly shorter for group A (28 min vs. 52 min, p = 0.01). For ERC, the success rate was not different between the groups (91.7% vs. 96.3%, p = 0.53), but the mean procedure time was significantly longer for group A (28.4 min vs. 4 min, p < 0.001). All endoscopic therapies could be successfully performed in both groups. No group A patients and five (23.8%) group B patients developed recurrent biliary stricture/stones requiring interventions during a mean follow-up period of 26.1 months. CONCLUSIONS: DBE-ERC was effective for both populations with biliary disorders. Reaching the blind end was more difficult but ERC was easier for patients with BEA in terms of procedure time rather than success rates.

Endoscopic Submucosal Dissection of Superficial Esophageal Neoplasms Is Feasible and Not Riskier for Patients with Liver Cirrhosis.

BACKGROUND: Esophageal endoscopic submucosal dissection (ESD) has rarely been reported for the treatment of cirrhotic patients. AIM: To report the results of ESD treatment of superficial esophageal neoplasms (SENs) for cirrhotic patients. METHODS: Forty patients with 50 consecutive SENs undergoing 46 sessions of ESD were retrospectively reviewed. The cirrhotic group included eight patients (11 SENs) with liver cirrhosis consisting of six patients classified as Child-Pugh class A liver cirrhosis and two patients classified as class B liver cirrhosis. Four patients (6 SENs) had coexisting esophageal varices. Parameters were compared between the cirrhotic patients and the non-cirrhotic controls (32 patients, 39 SENs). RESULTS: Platelet counts of the cirrhotic group were significantly lower, while international normalized ratio was significantly higher. When the cirrhotic group and non-cirrhotic group were compared, the mean tumor length (4 vs. 3.7 cm, p = 0.56) and median procedure time (15.1 vs. 11.5 min/cm2, p = 0.30) were similar. The en bloc resection rates were 81.8 and 89.7 % (p = 0.60). Within the cirrhotic group, both lesions without en bloc resection were patients with esophageal varices. The rates of submucosal disease for the cirrhotic group and non-cirrhotic groups were 54.5 and 25.6 % (p = 0.064), respectively, while the R0 resection rates were 77.8 and 94.3 % (p = 0.16), respectively. The two lesions without R0 resection in cirrhotic group had positive vertical but not horizontal margins due to submucosal invasion. Intraprocedural bleeding occurred more frequently in cirrhotic patients than non-cirrhotic patients (18.2 vs. 0 %, p = 0.045). None of the patients suffered from esophageal perforation, postoperative bleeding, or death that was related to the ESD. CONCLUSION: Esophageal ESD seems to be safely and can be effectively performed on cirrhotic patients, particularly those without severe liver dysfunction.

Concomitant Third Molar Removal During Sagittal Split Osteotomy of the Mandible.

It is described in textbook about management of third molar in orthognathic surgery that "ideally, the third molars should be removed 9 to 12 months before sagittal split osteotomy (SSO)." At the Chang Gung Craniofacial Center, the authors always remove mandibular third molars during SSO, because: removal of third molars at the same time of SSO could reduce psychological stress on patients by saving 1 surgical procedure under local anesthesia, better exposure of impacted third molars could be facilitated by sagittal split of buccal cortical plate, rigid fixation could be performed without difficulty by our fixation method using plates and screws crossover anterior oblique line. Strong force during the elevation of third molars, however, may result in the fracture of distal segment of SSO, where the buccal cortical plate is relatively thin because of the presence of third molar. Therefore, more care needs to be taken in the surgical technique, which is different from ordinary tooth extraction. In this paper, the details of surgical procedure of third molar removal during SSO were reported.