Success rates of fixation techniques on prevention of esophageal stent migration: a systematic review and meta-analysis.

BACKGROUND: Esophageal stenting is an important intervention for managing malignant and benign dysphagia, with stent migration representing a common drawback. This systematic review with meta-analysis aimed to assess the benefit of stent fixation over nonfixation. METHODS: A systematic search was performed in MEDLINE, Cochrane, Scopus, and ClinicalTrials.gov databases until January 2023 for comparative studies evaluating the migration rates of esophageal stents with versus without (control) fixation. The primary outcome was migration rate. Secondary outcomes included adverse event rate. A subgroup analysis stratified the results based on different fixation techniques: suturing, over-the-scope (OTS) clipping, and through-the-scope (TTS) clipping. Meta-analysis was based on a random effects model and the results were reported as odds ratios (ORs) with 95 %CIs. RESULTS: 10 studies (1014 patients) were included. The rate of stent migration was significantly lower after fixation (OR 0.20, 95 %CI 0.11-0.37; I2  = 59 %, P = 0.01). The adverse event rate was similar between fixation and control groups (OR 0.65, 95 %CI 0.28-1.52; I2  = 55 %, P = 0.06). In the subgroup analysis, all fixation techniques remained superior to nonfixation of stents (suturing OR 0.23, 95 %CI 0.10-0.53; OTS clips OR 0.31, 95 %CI 0.17-0.58; TTS clips OR 0.10, 95 %CI 0.03-0.38); however, only the OTS and TTS clip groups achieved nonsignificant heterogeneity (I2  = 0 %, P = 0.67 and P = 0.73, respectively). No difference between techniques was recorded for migration rates. CONCLUSION: Esophageal stent fixation was associated with significantly lower migration rates compared with nonfixation of stents, regardless of fixation technique and stenting indication.

Risk of metastasis among patients diagnosed with high-risk T1 esophageal adenocarcinoma who underwent endoscopic follow-up.

Esophagectomy and lymphadenectomy have been the standard of care for patients at high risk (HR) of lymph node metastasis following a diagnosis of early esophageal adenocarcinoma (OAC) after endoscopic resection (ER). However, recent cohorts suggest lymph node metastasis risk is lower than initially estimated, suggesting organ preservation with close endoscopic follow-up is a viable option. We report on the 3- and 5-year risk of lymph node/distant metastasis among patients diagnosed with early HR-T1 OAC undergoing endoscopic follow-up. Patients diagnosed with HR-T1a or T1b OAC following ER at a tertiary referral center were identified and retrospectively analyzed from clinical records between 2010 and 2021. Patients were included if they underwent endoscopic follow-up after resection and were divided into HR-T1a, low risk (LR)-T1b and HR-T1b cohorts. After ER, 47 patients underwent endoscopic follow-up for early HR OAC. In total, 39 patients had an R0 resection with a combined 3- and 5-year risk of LN/distant metastasis of 6.9% [95% confidence interval (CI): 1.8-25] and 10.9% (95% CI, 3.6-30.2%), respectively. There was no significant difference when stratifying by histopathological subtype (P = 0.64). Among those without persistent luminal disease on follow-up, the 5-year risk was 4.1% (95% CI, 0.6-26.1). Two patients died secondary to OAC with an all-cause 5-year survival of 57.5% (95% CI, 39.5-71.9). The overall risk of LN/distant metastasis for early HR T1 OAC was lower than historically reported. Endoscopic surveillance can be a reasonable approach in highly selected patients with an R0 resection and complete luminal eradication, but clear, evidence-based surveillance guidelines are needed.

Causes of morbidity in captive African lions (Panthera leo) in North America, 2001-2016.

The lion (Panthera leo) is an iconic resident of zoos and wild animal parks throughout the world. Regular assessment of the morbidity of captive lions is necessary to address wellness concerns and improve the healthcare and management of this vulnerable species. In an effort to understand disease morbidity broadly and guide future inquiries into captive lion health, we distributed a questionnaire that emphasized diseases of organ systems rather than individual diagnoses. We sent the questionnaire to 108 American Zoo and Aquarium Association (AZA) institutions housing lions between 2001 and 2016. Fifty-six facilities responded of which 32 responses had usable data for 111 lions. Responses were compiled and analyzed with respect to age, class, and sex. Neoplasia, renal disease, and dental disease were the most common causes of morbidity in these captive lions. Older animals generally experienced a higher prevalence of multiple types of disease. Three cases of hypertrophic cardiomyopathies (HCM) were reported in nearly 40% (3/8) of cardiovascular diseases and 3% (3/111) of disease cases overall, which is the first report of HCM in lions, to the authors' knowledge. There is a relative paucity of literature on lion and large felid cardiovascular conditions, which suggests that this may be an understudied area of lion health. This broad assessment of morbidities present in captive lion populations aimed to identify key areas for further research and screenings. Management priorities of captive lions should include prevention strategies for dental disease and trauma, frequent screening for renal disease and neoplasia, and further research into cardiovascular health.

Hepatitis E virus infection and acute non-traumatic neurological injury: A prospective multicentre study.

BACKGROUND & AIMS: Hepatitis E virus (HEV) has been associated with a number of neurological syndromes, but causality has not yet been established. The aim of this study was to explore the relationship between HEV and neurological illness by prospective HEV testing of patients presenting with acute non-traumatic neurological injury. METHODS: Four hundred and sixty-four consecutive patients presenting to hospital with acute non-traumatic neurological illnesses were tested for HEV by serology and PCR from four centres in the UK, France and the Netherlands. RESULTS: Eleven of 464 patients (2.4%) had evidence of current/recent HEV infection. Seven had HEV RNA identified in serum and four were diagnosed serologically. Neurological cases in which HEV infection was found included neuralgic amyotrophy (n=3, all PCR positive); cerebral ischemia or infarction (n=4); seizure (n=2); encephalitis (n=1); and an acute combined facial and vestibular neuropathy (n=1). None of these cases were clinically jaundiced and median ALT at presentation was 24IU/L (range 8-145). Cases of HEV-associated neuralgic amyotrophy were found in each of the participating countries: all were middle-aged males with bilateral involvement of the brachial plexus. CONCLUSIONS: In this cohort of patients with non-traumatic neurological injury, 2.4% had evidence of HEV infection. Symptoms of hepatitis were mild or absent and no patients were jaundiced. The cases of HEV-associated neuralgic amyotrophy had similarities with other HEV-associated cases described in a large retrospective study. This observation supports a causal relationship between HEV and neuralgic amyotrophy. To further understand the relevance of HEV infection in patients with acute neurological illnesses, case-control studies are warranted. Lay summary: Hepatitis E virus (HEV), as its name suggests, is a hepatotropic virus, i.e. it causes damage to the liver (hepatitis). Our findings show that HEV can also be associated with a range of injury to the nervous system.

Unraveling the Mechanisms of Vestibular Neuron Formation from Human Induced Pluripotent Stem Cells.

The development of in vitro models that accurately recapitulate the complex cellular and molecular interactions of the inner ear is crucial for understanding inner ear development, function, and disease. In this study, we utilized a customized microfluidic platform to generate human induced pluripotent stem cell (hiPSC)-derived three-dimensional otic sensory neurons (OSNs). hiPSC-derived otic neuronal progenitors (ONPs) were cultured in hydrogel-embedded microfluidic channels over a 40-day period. Careful modulation of Wnt and Shh signaling pathways was used to influence dorsoventral patterning and direct differentiation toward a vestibular neuron lineage. After validating the microfluidic platform, OSN spheroid transcription factor and protein expression were assessed using real-time quantitative polymerase chain reaction (RT-qPCR), immunocytochemistry, and flow cytometry. The results demonstrated the successful differentiation of hiPSCs into ONPs and subsequent divergent differentiation into vestibular neuronal lineages, as evidenced by the expression of characteristic markers. Overall, our microfluidic platform provides a physiologically relevant environment for the culture and differentiation of hiPSCs, offering a valuable tool for studying inner ear development, disease and drug screening, and regenerative medicine applications.

Peroral endoscopic myotomy for the management of symptomatic cricopharyngeal bar (C-POEM): a case series and video demonstration.

Background: A cricopharyngeal bar refers to a radiological description of a prominent cricopharyngeal muscle. While these may be incidental, they can lead to significant oropharyngeal dysphagia due to incoordination of the upper esophageal sphincter and true luminal narrowing. Various treatments have been used for the management of cricopharyngeal bar, including botulinum toxin injection, dilation, and surgical myotomy. Cricopharyngeal peroral endoscopic myotomy (C-POEM) is a novel procedure that uses the principles of "third-space" endoscopy to treat symptomatic cricopharyngeal bar. Methods: We report a retrospective case series of 5 patients referred with oropharyngeal dysphagia to 2 UK tertiary referral centers between 2022 and 2023 who subsequently underwent C-POEM. Technical success was defined as completion of all steps of the C-POEM procedure and clinical success as a reduction in the pre-treatment Dakkak and Bennett score to ≤1, or 0 if the pre-treatment score was 1. Results: C-POEM was associated with a technical success of 100% and clinical success of 100% over a median follow up of 2 months (interquartile range 1-8). There was 1 adverse event due to a small mucosal defect and associated leak on barium swallow, which was the result of difficult access during mucosal closure. This was managed conservatively with antibiotics. A step-by-step video demonstration of the procedure is provided. Conclusion: C-POEM offers an alternative upfront therapy for symptomatic cricopharyngeal bar, but should be undertaken by endoscopists with significant experience in third-space endoscopy in view of the difficulty of working within the hypopharynx.

The endoscopic management of oesophageal strictures.

An oesophageal stricture refers to a narrowing of the oesophageal lumen, which may be benign or malignant. The cardinal feature is dysphagia, and this may result from intrinsic oesophageal disease or extrinsic compression. Oesophageal strictures can be further classified as simple or complex depending on stricture length, location, diameter, and underlying aetiology. Many endoscopic options are now available for treating oesophageal strictures including dilatation, injectional therapy, stenting, stricturotomy, and ablation. Self-expanding metal stents have revolutionised the palliation of malignant dysphagia, but oesophageal dilatation with balloon or bougienage remains first-line therapy for most benign strictures. The increase in endoscopic and surgical interventions on the oesophagus has seen more benign refractory oesophageal strictures that are difficult to treat, and often require advanced endoscopic techniques. In this review, we provide a practical overview on the evidence-based management of both benign and malignant oesophageal strictures, including a practical algorithm for managing benign refractory strictures.

Hemospray® (hemostatic powder TC-325) as monotherapy for acute gastrointestinal bleeding: a multicenter prospective study.

Background: Hemostatic powders are used as second-line treatment in acute gastrointestinal (GI) bleeding (AGIB). Increasing evidence supports the use of TC-325 as monotherapy in specific scenarios. This prospective, multicenter study evaluated the performance of TC-325 as monotherapy for AGIB. Methods: Eighteen centers across Europe and USA contributed to a registry between 2016 and 2022. Adults with AGIB were eligible, unless TC-325 was part of combined hemostasis. The primary endpoint was immediate hemostasis. Secondary outcomes were rebleeding and mortality. Associations with risk factors were investigated (statistical significance at P≤0.05). Results: One hundred ninety patients were included (age 51-81 years, male: female 2:1), with peptic ulcer (n=48), upper GI malignancy (n=79), post-endoscopic treatment hemorrhage (n=37), and lower GI lesions (n=26). The primary outcome was recorded in 96.3% (95% confidence interval [CI]: 92.6-98.5) with rebleeding in 17.4% (95%CI 11.9-24.1); 9.9% (95%CI 5.8-15.6) died within 7 days, and 21.7% (95%CI 15.6-28.9) within 30 days. Regarding peptic ulcer, immediate hemostasis was achieved in 88% (95%CI 75-95), while 26% (95%CI 13-43) rebled. Higher ASA score was associated with mortality (OR 23.5, 95%CI 1.60-345; P=0.02). Immediate hemostasis was achieved in 100% of cases with malignancy and post-intervention bleeding, with rebleeding in 17% and 3.1%, respectively. Twenty-six patients received TC-325 for lower GI bleeding, and in all but one the primary outcome was achieved. Conclusions: TC-325 monotherapy is safe and effective, especially in malignancy or post-endoscopic intervention bleeding. In patients with peptic ulcer, it could be helpful when the primary treatment is unfeasible, as bridge to definite therapy.

Localised intestinal Kaposi sarcoma in a patient with non-coeliac seronegative villous atrophy.

Seronegative villous atrophy (SNVA) is a diagnostic challenge for gastroenterologists, which is defined by villous atrophy and negative coeliac serology. Non-coeliac forms of SNVA, such as autoimmune enteropathy, can be life-threatening leading to intractable diarrhoea and severe malabsorption that require systemic immunosuppression. When all known causes have been excluded, it is termed idiopathic villous atrophy (IVA). We present a case of non-coeliac SNVA complicated by Kaposi sarcoma (KS). A previously well HIV-negative man in his 30s presented with a 4-month history of watery diarrhoea and 25 kg weight loss. After prolonged investigation, he was diagnosed with non-coeliac SNVA without an identified aetiology that would be consistent with IVA. Clinical recovery was achieved with parenteral nutrition for type II intestinal failure and immunosuppression using high-dose corticosteroids. On subsequent gastroscopy, he was diagnosed with localised intestinal KS prompting cessation of all immunosuppression but remained in clinical remission.

Lynch syndrome: from detection to treatment.

Lynch syndrome (LS) is an inherited cancer predisposition syndrome associated with high lifetime risk of developing tumours, most notably colorectal and endometrial. It arises in the context of pathogenic germline variants in one of the mismatch repair genes, that are necessary to maintain genomic stability. LS remains underdiagnosed in the population despite national recommendations for empirical testing in all new colorectal and endometrial cancer cases. There are now well-established colorectal cancer surveillance programmes, but the high rate of interval cancers identified, coupled with a paucity of high-quality evidence for extra-colonic cancer surveillance, means there is still much that can be achieved in diagnosis, risk-stratification and management. The widespread adoption of preventative pharmacological measures is on the horizon and there are exciting advances in the role of immunotherapy and anti-cancer vaccines for treatment of these highly immunogenic LS-associated tumours. In this review, we explore the current landscape and future perspectives for the identification, risk stratification and optimised management of LS with a focus on the gastrointestinal system. We highlight the current guidelines on diagnosis, surveillance, prevention and treatment and link molecular disease mechanisms to clinical practice recommendations.

Metabolic and Bariatric Endoscopy: A Mini-Review.

We are currently in a worldwide obesity pandemic, which is one of the most significant health problems of the 21st century. As the prevalence of obesity continues to rise, new and innovate treatments are becoming available. Metabolic and bariatric endoscopic procedures are exciting new areas of gastroenterology that have been developed as a direct response to the obesity crisis. These novel interventions offer a potentially reversible, less invasive, safer, and more cost-effective method of tackling obesity compared to traditional bariatric surgery. Minimally invasive endoscopic treatments are not entirely novel, but as technology has rapidly improved, many of the procedures have been proven to be extremely effective for weight loss and metabolic health, based on high-quality clinical trial data. This mini-review examines the existing evidence for the most prominent metabolic and bariatric procedures, followed by a discussion on the future trajectory of this emerging subspecialty.

Intralesional application of ribavirin in two American flamingos (Phoenicopterus ruber) with poxvirus infection.

We report the successful treatment of poxvirus lesions in two juvenile American flamingos (Phoenicopterus ruber) with experimental low-dose intralesional ribavirin injection. In the first flamingo, the size and location of a beak verrucosity interfered with feeding, and after multiple surgical interventions, an experimental therapy of low-dose intralesional ribavirin was implemented with close blood parameter monitoring to minimize any potential side effects due to systemic antiviral administration. The second flamingo had a poxvirus lesion on the tibiotarsus, which recurred after unsuccessful conservative medical treatment and surgical intervention and a course of intralesional ribavirin therapy was implemented. Regression of the lesions in both flamingos commenced within 3 days of ribavirin treatment resulting in complete resolution within 6 weeks of onset of ribavirin treatment.

Application of supervised machine learning algorithms for the evaluation of utricular function on patients with Meniere's disease: utilizing subjective visual vertical and ocular-vestibular-evoked myogenic potentials.

BACKGROUND: Research on the otolith organs remains inconclusive. OBJECTIVES: This study seeks to further elucidate utricular function in patients with Meniere's disease (MD) in three ways: (1) We aimed to disambiguate the role of the Subjective Visual Vertical (SVV) and Ocular Vestibular Evoked Myogenic Potential (o-VEMP) tests regarding which utricular subsystem each is measuring. (2) We sought to characterize the acute and chronic state of MD by identifying differences in the relationship of SVV and o-VEMP results across patients with acute and chronic MD. (3) We attempted to find a machine-learning algorithm that could predict acute versus chronic MD using SVV and o-VEMP. METHODS: A prospective study with ninety subjects. RESULTS: (1) SVV and o-VEMP tests were found to have a moderate linear relationship in patients with acute MD, suggesting each test measures a different utricular subsystem. (2) Regression analyses statistically differed across the two patient populations, suggesting that SVV results were normalized in chronic MD patients. (3) Logistic regression and Naïve Bayes algorithms were found to predict acute and chronic MD accurately. SIGNIFICANCE: A better understanding of what diagnostic tests measure will lead to a better classification system for MD and more targeted treatment options in the future.

Endoscopic Management of Dysplastic Barrett's Oesophagus and Early Oesophageal Adenocarcinoma.

Barrett's oesophagus is a pathological condition whereby the normal oesophageal squamous mucosa is replaced by specialised, intestinal-type metaplasia, which is strongly linked to chronic gastro-oesophageal reflux. A correct endoscopic and histological diagnosis is pivotal in the management of Barrett's oesophagus to identify patients who are at high risk of progression to neoplasia. The presence and grade of dysplasia and the characteristics of visible lesions within the mucosa of Barrett's oesophagus are both important to guide the most appropriate endoscopic therapy. In this review, we provide an overview on the management of Barrett's oesophagus, with a particular focus on recent advances in the diagnosis and recommendations for endoscopic therapy to reduce the risk of developing oesophageal adenocarcinoma.

Bridging the electrode-neuron gap: finite element modeling of in vitro neurotrophin gradients to optimize neuroelectronic interfaces in the inner ear.

Although cochlear implant (CI) technology has allowed for the partial restoration of hearing over the last few decades, persistent challenges (e.g., poor performance in noisy environments and limited ability to decode intonation and music) remain. The "electrode-neuron gap" is inherent to these challenges and poses the most significant obstacle to advancing past the current plateau in CI performance. We propose the development of a "neuro-regenerative nexus"-a biological interface that doubly preserves native spiral ganglion neurons (SGNs) while precisely directing the growth of neurites arising from transplanted human pluripotent stem cell (hPSC)-derived otic neuronal progenitors (ONPs) toward the native SGN population. We hypothesized that the Polyhedrin Delivery System (PODS®-recombinant human brain-derived neurotrophic factor [rhBDNF]) could stably provide the adequate BDNF concentration gradient to hPSC-derived late-stage ONPs to facilitate otic neuronal differentiation and directional neurite outgrowth. To test this hypothesis, a finite element model (FEM) was constructed to simulate BDNF concentration profiles generated by PODS®-rhBDNF based on initial concentration and culture device geometry. For biological validation of the FEM, cell culture experiments assessing survival, differentiation, neurite growth direction, and synaptic connections were conducted using a multi-chamber microfluidic device. We were able to successfully generate the optimal BDNF concentration gradient to enable survival, neuronal differentiation toward SGNs, directed neurite extension of hPSC-derived SGNs, and synaptogenesis between two hPSC-derived SGN populations. This proof-of-concept study provides a step toward the next generation of CI technology. STATEMENT OF SIGNIFICANCE: Our study demonstrates that the generation of in vitro neurotrophin concentration gradients facilitates survival, neuronal differentiation toward auditory neurons, and directed neurite extension of human pluripotent stem cell-derived auditory neurons. These findings are indispensable to designing a bioactive cochlear implant, in which stem cell-derived neurons are integrated into a cochlear implant electrode strip, as the strategy will confer directional neurite growth from the transplanted cells in the inner ear. This study is the first to present the concept of a "neuro-regenerative nexus" congruent with a bioactive cochlear implant to eliminate the electrode-neuron gap-the most significant barrier to next-generation cochlear implant technology.

Imaging of trapped ions with a microfabricated optic for quantum information processing.

Trapped ions are a leading system for realizing quantum information processing (QIP). Most of the technologies required for implementing large-scale trapped-ion QIP have been demonstrated, with one key exception: a massively parallel ion-photon interconnect. Arrays of microfabricated phase Fresnel lenses (PFL) are a promising interconnect solution that is readily integrated with ion trap arrays for large-scale QIP. Here we show the first imaging of trapped ions with a microfabricated in-vacuum PFL, demonstrating performance suitable for scalable QIP. A single ion fluorescence collection efficiency of 4.2±1.5% was observed. The depth of focus for the imaging system was 19.4±2.4 µm and the field of view was 140±20 µm. Our approach also provides an integrated solution for high-efficiency optical coupling in neutral atom and solid-state QIP architectures.