Taylorstout2062

People with cystic fibrosis (CF) experience digestive symptoms but the mechanisms are incompletely understood. Here we explore causes and consequences of slower gastrointestinal transit using magnetic resonance imaging (MRI). Twelve people with CF and 12 healthy controls, matched for age and gender, underwent MRI scans, both fasted and after standardised meals, over 6.5 h. Fasted small bowel motility scores were lower in CF than in controls. No difference in ascending colon chyme T1 was detected. The difference in texture between small bowel and colon contents, seen in health, was diminished in CF. The ascending colon in CF participants had an abnormal appearance compared to controls. MRI offers unique potential to evaluate gut luminal content, colonic mucosa and intestinal motor activity. These new data support the theoretical cycle of desiccation, dysmotility and delayed transit as a cause of gastrointestinal symptoms in CF.

Low body mass index (BMI) may influence lung transplant decisions for patients with advanced cystic fibrosis (CF) lung disease.

Determine whether patients with advanced CF lung disease and BMI ≤17kg/m

are less likely to be listed for lung transplant or have a higher risk of death without listing compared to those with higher BMI.

Using merged United Network for Organ Sharing and CF Foundation Patient Registries, we identified adults with onset of advanced lung disease (FEV

≤ 40% predicted) between May-2005 and December-2016. We analyzed survival using competing risks regression with cause-specific risks of listing for lung transplant and death without listing. BMI ≤ 17kg/m

was our predictor.

Among 5,121 CF patients with advanced lung disease, 23% were listed for lung transplant (n=1,201), 23% died without listing (n=1,190), and 44% were alive without listing (n=2,730) as of December-2016. Patients with BMI ≤ 17kg/m

were less likely to be listed for transplant (HR 0.69; 95% CI 0.57, 0.83) and more likely to die without listing (HR 1.63; 95% CI 1.41, 1.88). We identified important regional variations in the likelihood of referral and listing, based on BMI.

Patients with advanced CF lung disease and BMI ≤ 17kg/m

are less likely to be listed for lung transplant and have a higher risk of dying without listing, compared to those with higher BMI. Regional differences suggest access to transplant for malnourished CF patients may be limited by location.

Patients with advanced CF lung disease and BMI ≤ 17 kg/m2 are less likely to be listed for lung transplant and have a higher risk of dying without listing, compared to those with higher BMI. Regional differences suggest access to transplant for malnourished CF patients may be limited by location.

In cystic fibrosis (CF), loss of CF transmembrane conductance regulator (CFTR)-dependent bicarbonate secretion precipitates the accumulation of viscous mucus in the lumen of respiratory and gastrointestinal epithelial tissues. We investigated whether the combination of elexacaftor (ELX), ivacaftor (IVA) and tezacaftor (TEZ), apart from its well-documented effect on chloride transport, also restores Phe508del-CFTR-mediated bicarbonate transport.

Epithelial monolayers were cultured from intestinal and biliary (cholangiocyte) organoids of homozygous Phe508del-CFTR patients and controls. Transcriptome sequencing was performed, and bicarbonate and chloride transport were assessed in the presence or absence of ELX/IVA/TEZ, using the intestinal current measurement technique.

ELX/IVA/TEZ markedly enhanced bicarbonate and chloride transport across intestinal epithelium. In biliary epithelium, it failed to enhance CFTR-mediated bicarbonate transport but effectively rescued CFTR-mediated chloride transport, known to be requisite for bicarbonate secretion through the chloride-bicarbonate exchanger AE2 (SLC4A2), which was highly expressed by cholangiocytes. Biliary but not intestinal epithelial cells expressed an alternative anion channel, anoctamin-1/TMEM16A (ANO1), and secreted bicarbonate and chloride upon purinergic receptor stimulation.

ELX/IVA/TEZ has the potential to restore both chloride and bicarbonate secretion across CF intestinal and biliary epithelia and may counter luminal hyper-acidification in these tissues.

ELX/IVA/TEZ has the potential to restore both chloride and bicarbonate secretion across CF intestinal and biliary epithelia and may counter luminal hyper-acidification in these tissues.

Diabetes related distress (DRD) is a negative emotional reaction to stresses associated with diabetes mellitus (DM) and its management. This study estimated the burden of DRD and self-reported adherence to treatment (SRAT) among patients with DM and investigated their relationship with glycemic control.

A cross sectional study of consented 157 diabetics was conducted using the17-item Diabetes Distress Scale (DDS). It measures distress at four subscales Emotional Burden (EB), Physician-related (PD), Regimen-related (RD) and Interpersonal Distress (ID). SRAT was assessed using Morisky's scale. Glycemic control was assessed using the most recent HbA1c results. Multivariable linear regression analysis was used for adjustment of confounders and bootstrap Confidence Interval was used to test for the occurrence of mediating effect.

Average age was 44.5 ± 16.0 years, 65% were females, 79% had type 2 DM and nearly 55% has had DM for more than 7 years and the average HbA1c was 8.9 ± 2.2%. Clinically significant D highlights the clinical role of DRD and clarifies the process by which distress affect the outcome of DM management.

One-anastomosis gastric bypass (OAGB) is a well established surgical procedure for morbid obesity. There are ongoing speculations and a debate regarding biliary reflux (BR) following OAGB. Studies considered OAGB as a risk for symptomatic and asymptomatic BR and marginal ulceration. The aim of the study was to evaluate the rate of gastroesophageal reflux disease (GERD) and esophagitis in microscopic and macroscopic evaluations among post OAGB patients diagnosed by means of upper endoscopy (UE) with a mucosal biopsy, and to assess the influence of comorbidities and medical history on endoscopic findings.

Patients operated between 1st January 2016 to 31st December 2017 were schedule, two years after OAGB for UE with a biopsy. In all cases, biopsies from the distal esophagus were obtained. All patients received a validated GERD-Health-Related Quality of Life questionnaire to assess their current symptoms.

Fifty patients were finally enrolled in the study. Twenty-four (48%) had grade A or B esophagitis. Four patients (8%) had endoscopically suspected esophageal metaplasia (ESEM). 34/50 (68%) patients had various histopathological esophageal changes, based on the conducted endoscopy, among which four cases of Barrett's esophagus were observed.

Despite the high rates of esophagitis in our cohort, most of the patients did not report any symptoms which confirm the thesis of the essential role of asymptomatic bile reflux following OAGB. Theoretically, chronic bile reflux can degenerate Barrett's esophagus into esophageal cancer.

Despite the high rates of esophagitis in our cohort, most of the patients did not report any symptoms which confirm the thesis of the essential role of asymptomatic bile reflux following OAGB. Theoretically, chronic bile reflux can degenerate Barrett's esophagus into esophageal cancer.

To date, no approved sealants for the prevention of postoperative pancreatic fistulas (POPFs) or bile leakage are available. The aim of the study is to assess the feasibility of a new synthetic and biodegradable polyurethane-based sealant patch (PBSP) for hepato-pancreato-biliary (HPB) surgery.

Benchmarking of the PBSP with commercially available products with a historical use in HPB surgery (Tachosil®, Hemopatch®, Surgicel® and Veriset®) was followed by performance testing in randomized controlled porcine animal studies. These studies focused on haemostasis as well as the prevention of POPFs and bile leakage.

The newly designed PBSP demonstrated the strongest adherence to liver tissue compared to Tachosil®, Hemopatch® and Veriset®. The new patch was the only patch with complete intra- and postoperative hemostasis (72h after application) compared to Tachosil and Veriset in a porcine liver abrasion study on 12 animals. In addition, the new patch demonstrably prevents the development of POPFs. The rate of postoperative pancreatitis and clinically relevant POPFs was significantly lower compared to the control groups in a porcine pancreatic fistula model based on 14 animals (14-day follow-up). Furthermore, the incidence of biloma after 7 days, considered as significant bile leakage, was significantly lower in the new PBSP compared to the Veriset® group. The PBSP was as effective as suturing in a porcine bile leakage model (7-day follow-up).

The PBSP induces constant hemostasis in the context of liver resection and prevents pancreatic fistulas and bile leakage. The promising preclinical data implicate clinical trials for further evaluation of this newly developed patch.

The PBSP induces constant hemostasis in the context of liver resection and prevents pancreatic fistulas and bile leakage. The promising preclinical data implicate clinical trials for further evaluation of this newly developed patch.Diffuse large B cell lymphoma (DLBCL) is an aggressive malignancy that has been traditionally treated with anthracycline-based chemotherapy, but approximately one-third of patients relapse after first-line therapy or have primary refractoriness. In this focused review, we discuss the 7 novel Food & Drug Administration (FDA)-approved medications for relapsed/refractory (R/R) DLBCL. We describe 5 CD19-targeted therapies, 3 of which are chimeric antigen receptor (CAR)-T cell therapies. We also highlight novel non-cell-based targeted therapies and discuss optimal sequencing considerations based on the goal of treatment, with an emphasis on CAR-T cell therapy as curative intent. We consider the limited tolerability of certain novel agents, prospects for elderly patients, and financial aspects of these approaches. We discuss advantages and limitations of these targeted therapies based on seminal clinical trials. Finally, we summarize ongoing trials involving promising agents making their way into the pharmacologic pipeline. These therapies include allogeneic CAR-T treatments and multi-antigen targeting therapies such as the CD19/CD22 CAR-T and the CD3/CD20 bispecific antibodies mosunetuzumab and odronextamab. We summarize our approach based on the best available evidence as we enter 2022.

Bariatric surgery has shown an improvement in obesity and obesity-related disease in many clinical trials and single center studies. However, real-world data, including data from non-centers of excellence, is sparse.

To provide clinical outcomes of patients who underwent bariatric surgery in real-world clinical setting.

Academic Institution.

Adults with obesity undergoing Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and a control group (CG) between 2007 and 2019 were identified. The CG represented patients with a previous visit to a bariatric surgeon without a subsequent surgery. Cohorts were matched on age, gender, ethnicity, baseline body mass index (BMI), and presence of diabetes and hypertension. Groups were compared in terms of co-morbidities, weight loss, and chronic conditions for three years.

A total of 61 313 patients were identified. From these, 14 916 RYGB and 20 867 SG patients were matched to the CG (n = 16 562). click here The median BMI loss three years after surgery was 28.7% (interquartile range [IQR] 20.