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Untreated cystathionine β-synthase (CBS) deficiency in humans is characterized by extremely elevated plasma total homocysteine (tHcy>200 µM), with thrombosis as the major cause of morbidity. Treatment with vitamins and diet leads to a dramatic reduction in thrombotic events, even though patients often still have severe elevations in tHcy (>80 µM). To understand the difference between extreme and severe hyperhomocysteinemia, we have examined two mouse models of CBS deficiency: Tg-hCBS Cbs-/- mice, with a mean serum tHcy of 169 µM, and Tg-1278T Cbs-/- mice, with a mean tHcy of 296 µM. Only Tg-1278T Cbs-/- animals exhibited strong biological phenotypes, including facial alopecia, osteoporosis, endoplasmic reticulum (ER) stress in the liver and kidney, and a 20% reduction in mean survival rime. Metabolic profiling of serum and liver reveals that Tg-1278T Cbs-/- mice have significantly elevated levels of free oxidized homocysteine but not protein-bound homocysteine in serum and elevation of all forms of homocysteine and S-adenosyl homocysteine in the liver compared to Tg-hCBS Cbs-/- mice. RNA profiling of livers indicate that Tg-1278T Cbs-/- and Tg-hCBS Cbs-/- mice have unique gene signatures, with minimal overlap. Our results indicate that there is a clear pathogenic threshold effect for tHcy and bring into question the idea that mild elevations in tHcy are directly pathogenic. [ABSTRACT FROM AUTHOR]

Background Achalasia can cause disabling symptoms that may substantially impair the quality of life. Peroral endoscopic myotomy (POEM) has shown promising Results in the management of achalasia. In this meta-analysis we have evaluated the feasibility and safety of single-session POEM with fundoplication (POEM+F) in patients with achalasia. Methods We reviewed several databases from inception to July 08, 2022, to identify studies evaluating the feasibility and/or safety of single-session POEM+F for patients with achalasia. Our outcomes of interest included the technical success of POEM+F, adverse events, esophagitis and wrap integrity on follow-up upper endoscopy, total procedure time, and fundoplication time. Pooled rates with 95% confidence intervals (CI) for outcomes were calculated using a random effect model. Heterogeneity was assessed using the I2 statistic. Results We included 4 studies with 90 patients. Pooled rates (95%CI) of technical success and adverse events were 92% (83-96%) and 5% (2-11%), respectively. Pooled rates (95%CI) of esophagitis and wrap integrity on follow-up upper endoscopy were 18% (11-30%) and 85% (43-98%) respectively. Pooled mean procedure time and fundoplication time were 113.2 (98.7-127.6) and 55.3 (43.7-66.8) min, respectively. Conclusions This meta-analysis demonstrates the feasibility and safety of POEM+F in patients with achalasia. More studies with long-term follow up are required to further validate these findings. [ABSTRACT FROM AUTHOR]

The electronic medical records of patients who underwent EMR for nonampullary duodenal polyps of >= 10 mm with prophylactic defect closure attempted with TTS suturing between March 2021 and May 2022 were reviewed. Table 1 Baseline characteristics of the 36 patients who underwent attempted TTS suturing of EMR defects and details of the resected duodenal polyps. Results Baseline characteristics A total of 36 patients (61 % women; mean [SD] age, 65 [12] years) underwent EMR of duodenal polyps followed by attempted defect closure with TTS suturing. In the five patients who underwent surveillance endoscopy, the TTS suturing system remained completely intact in one patient (20 %), partially intact in three (60 %), and was not seen in the remaining case. [Extracted from the article]

Background: Complete closure of large mucosal defects following colorectal ESD with through-the-scope clips (TTSC) is oftentimes not possible. We aimed to report an early experience of using a novel through-the-scope suturing system (TTSS) for closing large mucosal defects after colorectal ESD.Methods: We performed a retrospective, multi-center cohort study of consecutive patients who underwent attempted prophylactic defect closure using TTSS after colorectal ESD. The primary outcome was technical success in achieving complete defect closure, defined as (<5mm) residual mucosal defect in the closure line using TTSS with or without adjuvant TTSC.Results: Eighty-two patients with a median defect size of 30 mm [25-40] were included. Technical Success was achieved in 92.7% (n=76) using TTSS only in 44(53.7%) and a combination of TTSS to approximate the widest segment followed by complete closure with TTSCs in 32(39%) patients. Incomplete/partial closure, failure of appropriate TTSS deployment, and need for over-the-scope salvage closure methods were observed in 7.3%(n=6). One intraprocedural bleed, 1 delayed bleed, and 3 intraprocedural perforations were observed. There were no adverse events related to the placement of TTSS.Conclusion: TTSS is an effective and safe tool for the closure of large mucosal defects after colorectal ESD and is an alternative when complete closure with TTSC alone is not possible. [ABSTRACT FROM AUTHOR]

An abstract of the article "Antithrombotic Effects of Endogenous Expressed Activated Protein C (aPC) in Murine Models," by Joerg Schuettrumpf and colleagues is presented.

An abstract of the article "Assessing Hemostatic Efficacy of Continuous Expression of Factor VIIa after AAV-Mediated, Liver-Directed Gene Transfer in Hemophilia A and B Mice," by Alexander Schlachterman, Paris Margaritis, Majed Aljamali, Jianhua Liu, Valder Arruda and Katherine High is presented.

An abstract of the article "rAAV2 Integration Junctions Isolated without In Vivo Selection Bias Show a Preference to 5′ Regions of Open Reading Frames," by Fayaz R. Khazi, Alexander Schlachterman and Katherine A. High is presented.

To report the first successful full-term delivery following Per Oral Endoscopic Myotomy (POEM) performed during pregnancy. Achalasia is an esophageal motility disorder characterized by dysphagia, regurgitation, reflux, recurrent vomiting, and weight loss. Achalasia in pregnancy can affect nutritional status of the mother, and subsequently, the child, increasing morbidity and creating potential pregnancy complications. POEM is a novel endoscopic procedure which involves cutting the lower esophageal sphincter to allow food to pass, and is considered a safe and effective management option for achalasia in non-pregnant individuals. We discuss the case of a patient with achalasia and a prior Heller myotomy who presented with recrudescence of severe symptoms prompting evaluation and treatment with POEM. This is the first report of successful full-term delivery following POEM performed during pregnancy, demonstrating its feasibility and safety in this patient population when approached with a multidisciplinary team. [ABSTRACT FROM AUTHOR]

An abstract of the article "AAV-Mediated Gene Transfer to Endothelial Cells," by Mo-Ying Hsieh, Yi-Lin Liu, Alexander Schlachterman and Katherine A. High is presented.

An abstract of the article "Persistence of AAV Capsid in Transduced Cells," by Mo-Ying Hsieh, Fayaz R. Khazi, Alexander Schlachterman, Yi- Lin Liu and Katherine A. High is presented.