Endoscopic ultrasound-guided gastrojejunostomy for benign gastric outlet obstruction (GOO): a retrospective analysis of patients and outcomes.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ) has been well utilized in treating malignant gastric outlet obstructions (GOO) given its efficacy and lower risk profile compared to surgery. However, its efficacy and potential for use in patients with benign GOO who are poor surgical candidates is not well documented. The aim of this study was to examine the role of EUS-GJ in treatment of benign GOO in select patients. PATIENTS AND METHODS: This is a single-center, open-label, retrospective descriptive study that included all consecutive patients undergoing EUS-GJ to treat benign causes of GOO. Direct antegrade and direct retrograde methods were utilized. RESULTS: A total of 18 patients were included, 38.9% female with an average age of 63.3 years. Extrinsic GOO was present in (10 of 18) 55.5% of patients and intrinsic etiology was present in (8 of 18) 45.5% of patients. Technical success was achieved in 100% (18 of 18) patients and clinical success was achieved in 94% (17 of 18) patients. In total, 13 patients had follow-up endoscopy, 2 patients were treated relatively recently in time, 1 patient was lost to follow-up, and 2 patients died of other chronic illnesses. Stents remained in place for a median of 286 days (range 88-1444 days). In patients whose stents were removed, 75% (3 of 4) had extrinsic etiologies of GOO. CONCLUSIONS: This study reports a favorable long-term patency with excellent technical and clinical success of EUS-GJ in patients with benign GOO. Despite the limitations of sample size and retrospective nature, it adds to the extremely limited literature of EUS-GJ in management of patients with benign GOO.

How frequently MRI modifies thoracolumbar fractures' classification or decision-making? A systematic review and meta-analysis.

PURPOSE: To provide the first meta-analysis of the impact of magnetic resonance imaging (MRI) on thoracolumbar fractures (TLFs) classification and decision-making. METHODS: A systematic review was conducted following PRISMA guidelines. We searched PubMed, Scopus, Cochrane, and Web of Science from inception to June 30, 2023 for studies evaluating the change in TLFs classification and treatment decisions after MRI. The studies extracted key findings, objectives, and patient population. A meta-analysis was performed for the pooled frequency of change in AO fracture classification or treatment decisions from surgical to conservative or vice versa after MRI. RESULTS: This meta-analysis included four studies comprising 554 patients. The pooled frequency of change in TLFs classification was 17% (95% CI 9-31%), and treatment decision was 22% (95% CI 11-40%). An upgrade from type A to type B was reported in 15.7% (95% CI 7.2-30.6%), and downgrading type B to type A in 1.2% (95% CI 0.17-8.3%). A change from conservative to surgery recommendation of 17% (95% CI 5.0-43%) was higher than a change from surgery to conservative 2% (95% CI 1-34%). CONCLUSIONS: MRI can significantly change the thoracolumbar classification and decision-making, primarily due to upgrading type A to type B fractures and changing from conservative to surgery, respectively. These findings suggest that MRI could change decision-making sufficiently to justify its use for TLFs. Type A subtypes, indeterminate PLC status, and spine regions might help to predict a change in TLFs' classification. However, more studies are needed to confirm the association of these variables with changes in treatment decisions to set the indications of MRI in neurologically intact patients with TLFs. An interactive version of our analysis can be accessed from here: https://databoard.shinyapps.io/mri_spine/ .

A Systematic Review of Novel Therapies of Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive, cureless disease, characterized by increased pulmonary vascular resistance and remodeling, with subsequent ventricular dilatation and failure. New therapeutic targets are being investigated for their potential roles in improving PAH patients' symptoms and reversing pulmonary vascular pathology. METHOD: We aimed to address the available knowledge from the published randomized controlled trials (RCTs) regarding the role of Rho-kinase (ROCK) inhibitors, bone morphogenetic protein 2 (BMP2) inhibitors, estrogen inhibitors, and AMP-activated protein kinase (AMPK) activators on the PAH evaluation parameters. This systematic review (SR) was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CDR42022340658) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Overall, 5092 records were screened from different database and registries; 8 RCTs that met our inclusion criteria were included. The marked difference in the study designs and the variability of the selected outcome measurement tools among the studies made performing a meta-analysis impossible. However, the main findings of this SR relate to the powerful potential of the AMPK activator and the imminent antidiabetic drug metformin, and the BMP2 inhibitor sotatercept as promising PAH-modifying therapies. There is a need for long-term studies to evaluate the effect of the ROCK inhibitor fasudil and the estrogen aromatase inhibitor anastrozole in PAH patients. The role of tacrolimus in PAH is questionable. The discrepancy in the hemodynamic and clinical parameters necessitates defining cut values to predict improvement. The differences in the PAH etiologies render the judgment of the therapeutic potential of the tested drugs challenging. CONCLUSION: Metformin and sotatercept appear as promising therapeutic drugs for PAH. CLINICAL TRIALS REGISTRATION: This work was registered in PROSPERO (CDR42022340658).

Helicobacter Pylori-Negative MALT Lymphoma: A Series of Two Cases Presenting with Life-Threatening Upper Gastrointestinal Bleeding.

Mucosa-associated lymphoid tissue (MALT) lymphoma is a common cause of gastric lymphoma. Although most cases are associated with an H. pylori infection, approximately 10% are H. pylori-negative. Patients with gastric MALT lymphoma are usually asymptomatic or present with nonspecific symptoms such as abdominal pain, dyspepsia, weight loss, and occult gastrointestinal bleeding. In this report, we describe two patients with H. pylori-negative MALT lymphoma who both presented with acute upper gastrointestinal bleeding that led to hemodynamic instability. After resuscitation, emergent endoscopy was performed. Both patients had the t (11; 18) (q21; q21) translocation, which prompted direct treatment by radiotherapy.

Is Ustekinumab Effective in Refractory Crohn's Disease of the Pouch and Chronic Pouchitis? A Systematic Review.

Crohn's disease (CD) of the pouch and chronic pouchitis represent the most common long-term complications of total proctocolectomy and ileal pouch anal anastomosis (IPAA) for refractory ulcerative colitis (UC). These conditions are treated with multiple agents, including antibiotics, immunomodulators, and biologics. Among the latter, ustekinumab is approved for both CD and UC. We performed a systematic review to evaluate the efficacy of this anti-IL12/23 in CD of the pouch and chronic refractory pouchitis. Pubmed, Embase, Ovid, and the Cochrane Controlled Trials Register were searched to identify studies published until August 2020 investigating the use of ustekinumab for these conditions. Eighty-six eligible patients with IPAA-51 with CD of the pouch, 35 with chronic pouchitis-were identified from 2 retrospective studies and 5 case reports. Reported clinical response to ustekinumab was 63 and 85% in chronic pouchitis and CD of the pouch after 4-12 and 4-16 weeks, respectively. Clinical remission was reported in 10% of patients with chronic pouchitis and 27% of patients with CD of the pouch after 8-52 and 4-52 weeks of treatment, respectively. Endoscopic response was reported in 60% and 67% of patients with chronic pouchitis and CD of the pouch after 24-32 and 8-24 weeks of treatment respectively. Small sample sizes and large heterogeneity of therapy protocols/outcome definitions were significant studies limitations. In conclusion, there is a limited and inconclusive body of evidence suggesting that ustekinumab may be a therapeutic option for patients with chronic pouchitis and CD of the pouch refractory to other therapies.

Wireless Capsule Endoscopy for Diagnosis and Management of Post-Operative Recurrence of Crohn's Disease.

Despite aggressive medical therapy, many patients with Crohn's disease require surgical intervention over time. After surgical resection, disease recurrence is common. Ileo-colonoscopy and the Rutgeerts score are commonly used for diagnosis and monitoring of post-operative endoscopic recurrence. The latter is the precursor of clinical recurrence and therefore it impacts prognosis and patient management. However, due to the limited length of bowel assessed by ileo-colonoscopy, this procedure can miss out-of-reach, more proximal lesions in the small bowel. This limitation introduces an important uncertainty when evaluating post-operative relapse by ileo-colonoscopy. In addition, the Rutgeerts score 'per se' bears a number of ambiguities. Here we will discuss the pros and cons of ileo-colonoscopy and other imaging studies including wireless capsule endoscopy to diagnose and manage post-operative recurrence of Crohn's disease. A number of studies provide evidence that wireless capsule endoscopy is a potentially more accurate as well as less invasive and less costly alternative to conventional techniques including ileo-colonoscopy.

Role of microRNA-21 and microRNA-155 as biomarkers for bronchial asthma.

MicroRNA (miRNA)-21 and miRNA-155 are important regulators of gene expression of different immunological molecules. This study aimed to investigate the role of miRNA-21 and miRNA-155 as biomarkers in asthma by comparing their serum expression levels in asthmatic patients to those in healthy controls and correlating their levels with serum IL-4. The expression levels of miRNA-21 and miRNA-155 were evaluated by quantitative RT-PCR. Serum levels of IL-4 were determined using ELISA. Asthmatic patients showed significantly higher serum miRNA-21 and miRNA-155 expression levels compared to controls. A statistically significant positive correlation between the expression levels of miRNA-21 and IL-4 serum levels in asthmatic patients was detected. Nonetheless, no correlation was detected between miRNA-155 expression and each of IL-4 and miRNA-21. A receiver operating characteristic curve analysis showed that at a cut-off value of 1.37, the sensitivity of miRNA-21 as an asthma biomarker was 100% and the specificity was 95%. At a cut-off value of 1.96, the sensitivity of miRNA-155 as an asthma biomarker was 100% and the specificity was 100%. It can be concluded that miRNA-21 and miRNA-155 are potential non-invasive biomarkers in the diagnosis of eosinophilic asthma and its response to therapy.

'Re-PEGing': an endoscopic approach to inadvertent early removal of PEG tube.

Inadvertent removal of percutaneous endoscopic gastrostomy (PEG) tube shortly after placement creates the potential for gastric perforation and requires immediate attention. This problem has been addressed in the past with either observation or surgery. We describe our experience with the alternative approach of semi-urgent 're-PEGing'. Our results in seven patients were favorable.

Appendiceal sarcoidosis presenting as acute appendicitis.

Sarcoidosis is a chronic inflammatory multisystem disease. The stomach is the most commonly involved gastrointestinal organ. Symptomatic appendicular sarcoidosis is extremely rare. We present a case of a 49-year-old woman with abdominal pain. An ultrasound of the abdomen was suggestive of acute appendicitis. Laparoscopic appendectomy was performed and the pathology revealed nonnecrotizing granulomas. Biopsy of the mediastinal lymph nodes suggested noncaseating granulomas. She was treated with steroid therapy followed by mycophenolate mofetil. Our case demonstrates the importance of considering appendiceal sarcoid among the differentials in a patient with systemic sarcoidosis presenting with an acute abdomen.

Angry bowels breaking hearts: a case series.

Stress cardiomyopathy or Takotsubo cardiomyopathy (TCM) is transient left ventricular apical akinesis in the absence of angiographic evidence of corresponding obstructive coronary artery disease. A classic presentation is of chest pain following intense emotional or physical stress. Reports of stress-inducing triggers include acute respiratory failure, sudden death of a loved one, sympathomimetic drugs, pheochromocytoma crisis, diabetic ketoacidosis, and even earthquakes. We report three cases of intra-abdominal etiologies precipitating Takotsubo cardiomyopathy: two with small bowel obstruction, and one with Clostridium difficile colitis.

An unfortunate failure: multifocal hepatocellular carcinoma in a non-cirrhotic patient with chronic hepatitis C treated with ledipasvir/sofosbuvir.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the third highest cause of cancer mortality worldwide. Risk factors include chronic liver disease and cirrhosis of various causes including chronic hepatitis B and C. In cases of chronic hepatitis C virus (HCV), HCC usually does not manifest unless the liver has become cirrhotic. Fortunately, novel treatments for hepatitis C including ledipasvir/sofosbuvir can cure patients from their disease and as a result, may never develop cirrhosis and therefore, be at much lower risk of developing HCC. We present a patient with chronic HCV genotype 1a who was successfully treated with ledipasvir/sofosbuvir with documented sustained viral response, but 6 months later was found to have multifocal HCC with virus reactivation with no evidence of cirrhosis on imaging or biochemical testing. While novel antiviral agents for HCV lead to >90% cure rate, cure is defined as sustained viral response of only 12 weeks. This brings to light a new patient population who may require further follow-up than 3 months to ensure viral clearance. Furthermore, this patient developed HCC despite initial viral clearance and no evidence of cirrhosis, indicating possible oncogenic potential of HCV that is independent of cirrhosis that necessitates further investigation.

Variable toxicological response to the loss of OXPHOS through 1-methyl-4-phenylpyridinium-induced mitochondrial damage and anoxia in diverse neural immortal cell lines.

Immortal cell lines are used to investigate various aspects of neurodegeneration. These cells display high glycolytic turnover rate and produce an abundant amounts of lactate. Our previous studies indicate that these cells survive the loss of mitochondrial oxidative phosphorylation (OXPHOS) with ample glucose supply. In the current study, we investigate if cell type (w/variation in basal metabolic rate (MR)), can alter glucose utilization patterns which in turn may affect LC(50) for the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP(+)) in various cell lines. The data obtained indicate that cell lines MRs examined were generally consistent with the average of species adult body weight where mouse N-2A > rat-PC-12 > human SH-SY5Y. A higher MR was associated with accelerated utilization of glucose and earlier cell death with MPP(+): LC(50) mouse = 294 µM, rat = 695 µM, and human = 5.25 mM at 24 h. Cell death appears to be a function of the velocity by which glucose disappears, leading to the failure of glycolysis and subsequent halt of energy production. Similar effects were also observed at higher plating densities where the demand for glucose is amplified. A time-lapse study of MPP(+) toxicity (0-36 h) in N-2A cells indicates that an anaerobic shift occurs as early as 2 h (evidenced by a rise in lactate), followed by a descent in glucose concentrations at 4 h and exhaustion of glucose supplies at 22 h which was associated with the first detectable sign of cell death. It was also noted that MPP(+) toxicity was not associated with the generation of reactive oxygen species (O (2) (-) , H(2)0(2), and NO(2)) and was not attenuated by adding catalase or superoxide dismutase to the media. On the other hand, MPP(+) toxicity was reversed by providing additional supply of glucose, pyruvate ± mitochondrial monocarboxylate transporter blocker (α-cyano-4-HCA), or pyruvate ± pyruvate dehydrogenase inhibitor (octanoyl-CoA), suggesting that the exclusive anaerobic survival compensates for the loss of OXPHOS by MPP(+). To examine if neuroblastoma were capable of surviving the deprivation of O(2) for 24 h, a range of hypoxia to anoxia was established with various concentrations of dithionite. The data suggest that cell lines examined continue to thrive when incubated with high-glucose media (25 mM). In summary, vulnerability of immortal neuroblastoma cell lines to MPP(+) toxicity is dependent upon glucose concentrations within the media and cell MR, which indirectly dominates the velocity of glucose use and its end point disappearance, leading to cell death by ergogenic failure.