Safety of Pneumatic Dilation in Older Adults with Achalasia: An International Multicenter Cross-Sectional Study.

BACKGROUND: Pneumatic dilation (PD) is an effective first line treatment option for many patients with achalasia. PD use may be limited in adults with achalasia who are older than 65 because of concern for adverse events (AE), and less efficacious therapies are often utilized. We explored the periprocedural safety profile of PD in older adults. METHODS: An international real world cross-sectional study of patients undergoing PD between 2006-2020 in two tertiary centers. Thirty-day AEs were compared between older adults (65 and older) with achalasia and younger patients. RESULTS: A total of 252 patients underwent 319 PDs. In 319 PDs, 18 (5.7%) complications occurred: 6 (1.9%) perforations and 12 (3.8%) emergency department referrals with benign (non-perforation) chest pain, of which 9 (2.8%) were hospitalized. No bleeding or death occurred within 30 days. Perforation rates were similar in both age groups and across achalasia subtypes. Advanced age was protective of benign chest pain complications in univariate analysis, and the limited number of AEs precluded multivariable analysis. CONCLUSIONS: The safety of PD in older adults is at least comparable to that of younger patients and should be offered as an option for definitive therapy for older patients with achalasia. Our results may affect informed consent discussions.

Crohn's Disease Exclusion Diet for the Treatment of Crohn's Disease: Real-World Experience from a Tertiary Center.

The Crohn's Disease (CD) exclusion diet (CDED) has been shown to induce remission in pediatric and adult patients with CD. In this retrospective cohort study, we describe our real-world experience with the CDED at the inflammatory bowel disease (IBD) unit of the Tel Aviv Medical Center between 2018-2021. CD patients with multiple clinical presentations and disease phenotypes who initiated the diet were included. Indications for treatment, medical and nutritional data were collected from dietician clinic visits and medical records. Clinical and biomarker responses were determined. The CDED was recommended to 220 CD patients. Seventy-two patients were included in the analysis for a clinically active disease (n = 48) or for remission maintenance (n = 24). Among patients with a clinically active disease, 62.5% of patients achieved clinical remission at week 6 and at week 12. A positive association between high adherence to the CDED and clinical remission at week 12 was observed (adjusted OR = 7.6, 95% CI 1.07-55.2, p = 0.043). Among patients treated for remission maintenance, remission at week 12 was maintained among 83.3% of patients. We conclude that the CDED may be a promising intervention for multiple CD presentations and indications. These findings should be further validated in larger, prospective, controlled studies.

Octa-nonagenarians can perform video capsule endoscopy safely and with a higher diagnostic yield than 65-79-year-old patients.

BACKGROUND: Video capsule endoscopy (VCE) is an effective, noninvasive modality for small bowel (SB) investigation. Its usage in the older adults is rising. However, data in octa-nonagenarians regarding diagnostic yield and motility are lacking. Our aim was to evaluate and compare safety and efficacy of VCE between age subgroups of older adult patients. METHODS: This was a retrospective study of prospectively documented data. All consecutive VCEs of patients ≥65 years (01/2010-12/2017) were included. Patients unable to swallow the capsule or videos with significant recording technical malfunction were excluded. The cohort was divided into the younger group aged 65-79 years old and octa-nonagenarians aged ≥80 years old. Indications for referral, diagnostic yield and transit times were compared between groups. RESULTS: A total of 535 VCEs were performed in 499 older adult patients (51.2% males); 82.8% were 65-79 years old and 17.2% were ≥80 years old. The ≥80-year-old group had higher rates of clinically significant findings (52.7% vs. 40.0%, p = 0.025), active bleeding (12.5% vs. 6.5%, p = 0.053) and angioectasia (36.0% vs. 23.4%, p = 0.014). Crohn's disease was newly diagnosed in approximately 8% of the entire cohort and 12% of the ≥80 years old. Anemia was the most common indication in both groups, followed by overt bleeding in the ≥80-year-old group (25% vs. 9.9% in 65-79-year-old group, p < 0.001) and Crohn's disease in the 65-79 years old (17.2% vs. 5.4% in ≥80 years old, p = 0.004). Groups were comparable in transit time and cecal documentation rates. CONCLUSIONS: In octa-nonagenarians, VCE is as safe as in younger older-adults with a higher diagnostic yield of significant and treatable conditions.

Low serum vitamin D is independently associated with unexplained elevated ALT only among non-obese men in the general population.

INTRODUCTION AND OBJECTIVES: There are inconsistent findings on the association between human non-alcoholic fatty liver disease (NAFLD) and vitamin D, perhaps due to insufficient specificity for gender and obesity status. We aimed to assess whether serum levels of 25-hydroxyvitamin D are associated with unexplained elevated alanine aminotransferase (ALT) in general population across gender and body mass index (BMI) levels. MATERIALS AND METHODS: A cross-sectional analysis of a population-based cohort with a nationwide-distribution using electronic medical database. The population consisted of individuals aged 20-60 years who underwent blood tests for ALT and vitamin D. RESULTS: A total of 82,553 subjects were included (32.5% men, mean age 43.91±10.15 years). The prevalence of elevated ALT was higher among men and women with vitamin D insufficiency or deficiency, but in multivariate analysis, adjusting for: age, BMI, serum levels of glucose, total cholesterol, triglycerides, statin use and season, only the association among men remained significant for the vitamin D deficiency category (OR=1.16, 95%CI 1.04-1.29, P=0.010). Stratification by BMI revealed that only among normal weight and overweight men vitamin D deficiency was associated with elevated ALT (OR=1.27, 95%CI 1.01-1.59, P=0.041 and OR=1.27, 95%CI 1.08-1.50, P=0.003, respectively). No independent association was shown among women at all BMI categories. CONCLUSIONS: In a "real-life" general population, the association between vitamin D deficiency and unexplained elevated ALT is specific for non-obese men. The clinical significance of vitamin D for human NAFLD should be further elucidated with attention for a modifying effect of gender and adiposity.

Sortilin deficiency improves the metabolic phenotype and reduces hepatic steatosis of mice subjected to diet-induced obesity.

BACKGROUND & AIMS: Sortilin traffics newly synthesized molecules from the trans-Golgi apparatus along secretory pathways to endosomes, lysosomes or to the cell surface. Sortilin trafficking of acid sphingomyelinase (aSMase) may regulate ceramide levels, a major modulator of insulin signalling. We therefore tested whether sortilin deficiency reduces hepatic and adipose tissue aSMase activity, improving insulin sensitivity in diet-induced obesity (DIO). METHODS: DIO in C57BL/6 (WT) and sortilin(-/-) mice was induced by high-fat diet feeding for 10 weeks. RESULTS: Sortilin(-/-) mice gained less body weight and less visceral fat, despite similar food intake compared to WT type mice and had enhanced glucose uptake in insulin tolerance tests, which was further corroborated by enhanced hepatic pAkt expression. Sortilin deficiency led to attenuated hepatic steatosis, reduced expression of genes involved in lipogenesis, ceramide synthesis and inflammatory cytokine production and reduced activity of ceramide synthase 5/6 (CerS5/6). Sortilin(-/-) mice had reduced hepatic aSMase activity under both steady-state and DIO. Likewise, sortilin(-/-) hepatocytes displayed hypersensitivity to insulin, due to enhanced insulin receptor downstream signalling. In adipose tissue, sortilin(-/-) mice exhibited lower expression of inflammatory cytokines and lower expression and activity of CerS5/6. As in liver, adipose tissue displayed increased insulin signalling, accompanied by attenuated aSMase activity. CONCLUSIONS: Sortilin deficiency induces a beneficial metabolic phenotype in liver and adipose tissue upon DIO, mediated in part by reduced aSMase activity.

Long-acting glucose-dependent insulinotropic polypeptide ameliorates obesity-induced adipose tissue inflammation.

Obesity induces low-grade chronic inflammation, manifested by proinflammatory polarization of adipose tissue innate and adaptive resident and recruited immune cells that contribute to insulin resistance (IR). The glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that mediates postprandial insulin secretion and has anabolic effects on the adipose tissue. Importantly, recent evidence suggested that GIP is a potential suppressor of inflammation in several metabolic models. In this study, we aimed to investigate the immunoregulatory role of GIP in a murine model of diet-induced obesity (DIO) using the long-acting GIP analog [d-Ala(2)]GIP. Administration of [d-Ala(2)]GIP resulted in adipocytes of increased size, increased levels of adipose tissue lipid droplet proteins, indicating better lipid storage capacity, and reduced adipose tissue inflammation. Flow cytometry analysis revealed reduced numbers of inflammatory Ly6C(hi) monocytes and F4/80(hi)CD11c(+) macrophages, associated with IR. In addition, [d-Ala(2)]GIP reduced adipose tissue infiltration of IFN-γ-producing CD8(+) and CD4(+) T cells. Furthermore, [d-Ala(2)]GIP treatment induced a favorable adipose tissue adipokine profile, manifested by a prominent reduction in key inflammatory cytokines (TNF-α, IL-1ß, IFN-γ) and chemokines (CCL2, CCL8, and CCL5) and an increase in adiponectin. Notably, [d-Ala(2)]GIP also reduced the numbers of circulating neutrophils and proinflammatory Ly6C(hi) monocytes in mice fed regular chow or a high-fat diet. Finally, the beneficial immune-associated effects were accompanied by amelioration of IR and improved insulin signaling in liver and adipose tissue. Collectively, our results describe key beneficial immunoregulatory properties for GIP in DIO and reveal that its augmentation ameliorates adipose tissue inflammation and improves IR.

Prevalence and predictors of slow flow in angiographically normal coronary arteries.

BACKGROUND: One out of 5 patients undergoing coronary angiography has angiographically normal coronary arteries (ANCA). Some of them have abnormally slow coronary flow (SCF). The prevalence and causes of SCF in these patients are not clear. METHODS: We studied 114 consecutive patients with ANCA. Each angiogram was independently evaluated by 2 physicians unaware of all other clinical features of the case. Coronary flow (CF) was graded using the corrected TIMI Frame Count (cTFC) and Coronary Clearance Frame Count (CCFC) methodologies. SCF was defined as a cTFC exceeding the reported normal (mean cTFC + 2 SD) in each of the three major coronary arteries. The association between SCF and various clinical, inflammatory, and metabolic variables was tested using a multivariable analysis model. RESULTS: Thirty-nine (34%) patients had SCF. Inter-individual CF varied substantially among them (range 10-143 frames/sec, mean: 37 ± 22 frames/sec). The intra-individual CF did not vary: CF correlated well in the three major epicardial coronary arteries of a given individual (r = 0.7, p = 0.0001). Multivariable analysis revealed that current smoking was the most significant variable related to SCF (odds ratio = 4.7, p = 0.006, CI 95% 1.6-13.3). The SCF group included significantly more smokers (41% versus 15%, p = 0.002). CONCLUSIONS: SCF is a common finding (34%) among patients with angiographically normal coronary arteries. In these patients, slow flow is a systemic phenomenon that involves all three coronary arteries rather than a local event and is associated with current smoking.