Analysis of the Complicated Nonlinear Pharmacokinetics of Orally Administered Telmisartan in Rats Using a Stable Isotope-IV Method

This study aimed to kinetically analyze the nonlinear absorption and systemic exposure of telmisartan (TEL) after oral administration to rats by using a stable isotope-IV method. Rats were orally administered different dose of TEL, followed by the intravenous injection of 0.005 mg/kg of deuterium-labeled TEL (TEL-d3). Assuming that TEL-d3 shows same pharmacokinetic properties with TEL, systemic clearance (CL_tot), oral bioavailability (F_oral), and intestinal and hepatic availability (F_a*F_g, F_h) of TEL were calculated in each individual rat. AUC_po of TEL increased disproportionately with dose and showed a sigmoid-type relation, indicating the involvement of multi-nonlinear processes in oral absorption of TEL. F_a*F_g of TEL increased with dose at the low-dose range while decreased at the high-dose range. In contrast, F_h increased and CL_tot decreased significantly in the middle range (2 to 6 mg/kg). As main factors of nonlinearity, saturations of solubility, efflux transport in the intestine, and the hepatic uptake of TEL were indicated. In conclusion, this study demonstrated a high possibility of a stable isotope-IV method to characterize complicated pharmacokinetic properties of oral drugs in animals, which can help to consider the future risks in their clinical use.     

Indocyanine green loaded hyaluronan-derived nanoparticles for fluorescence-enhanced surgical imaging of pancreatic cancer

Pancreatic ductal adenocarcinoma is highly lethal and surgical resection is the only potential curative treatment for the disease. In this study, hyaluronic acid derived nanoparticles with physico-chemically entrapped indocyanine green, termed NanoICG, were utilized for intraoperative near infrared fluorescence detection of pancreatic cancer. NanoICG was not cytotoxic to healthy pancreatic epithelial cells and did not induce chemotaxis or phagocytosis, it accumulated significantly within the pancreas in an orthotopic pancreatic ductal adenocarcinoma model, and demonstrated contrast-enhancement for pancreatic lesions relative to non-diseased portions of the pancreas. Fluorescence microscopy showed higher fluorescence intensity in pancreatic lesions and splenic metastases due to NanoICG compared to ICG alone. The in vivo safety profile of NanoICG, including, biochemical, hematological, and pathological analysis of NanoICG-treated healthy mice, indicates negligible toxicity. These results suggest that NanoICG is a promising contrast agent for intraoperative detection of pancreatic tumors.     

脑出血微创术后继续出血危险因素分析及护理对策

目的 探讨高血压性脑出血（intracerebral hemorrhage ICH）微创颅内血肿穿刺引流术后继续出血的危险因素及护理措施.方法 98例ICH患者中,按微创术后有无继续出血分为两组.出血组20例为继续出血者,对照组78例为无继续出血者.统计分析患者有无饮酒史、术前血压、脑出血的部位、原发出血量、出血到微创手术的时间、穿刺部位、术后血压控制情况等临床资料.结果 微创颅内血肿穿刺术后继续出血与手术时间、术前血压增高、手术前后躁动、长期酗酒、血肿形态不规则等有关（P ＜0.05）.结论 酗酒、术前高血压、脑出血的形态、手术时间及患者躁动是引起术后继续出血的危险因素,应采取有效的具有针对性的护理对策.     

The burden of digestive disease across Europe: Facts and policies

The past decade has witnessed a significant increase in the incidence of GI diseases across Europe. There are clear differences in outcomes for patients in Europe based on geographical and economic differences, and there is a worrying inequality in the provision of healthcare across the continent. Recent demographic studies have highlighted the heavy burden of GI disease across Europe. There is increasing demand for endoscopic procedures which are becoming increasingly more complex and demand further expertise and training. A co-ordinated and cohesive approach to research, specialist training and healthcare funding is required to overcome these inequalities.     

Postural Orthostatic Tachycardia Syndrome: JACC Focus Seminar

Postural orthostatic tachycardia syndrome (POTS), the most common form of orthostatic intolerance in young people, affects approximately 500,000 people in the United States alone, typically young women at the peak of their education and the beginning of their working lives. This is a heterogeneous disorder, the pathophysiology and mechanisms of which are not well understood. There are multiple contributing factors and numerous potential mimics. This review details the most current views on the potential causes, comorbid conditions, proposed subtypes, differential diagnoses, evaluations, and treatment of POTS from cardiological and neurological perspectives.     

Enhanced Recovery after Surgery (ERAS) Protocol Is a Safe and Effective Approach in Patients with Gastrointestinal Fistulas Undergoing Reconstruction: Results from a Prospective Study

Background and Aims: An enterocutaneous fistula (ECF) poses a major surgical problem. The definitive surgical repair of persistent fistulas remains a surgical challenge with a high rate of re-fistulation and mortality, and the reasons for that is not the surgical technique alone. Enhanced Recovery after Surgery (ERAS^®) is an evidence-based multimodal perioperative protocol proven to reduce postoperative complications. The aim of the study was to assess the clinical value of the ERAS protocol in surgical patients with ECF. Methods: ERAS protocol was used in all patients scheduled for surgery for ECF at the Stanley Dudrick’s Memorial Hospital in Skawina between 2011 and 2020. A multidisciplinary team (MDT) was in charge of the program and performed annual audits. A consecutive series of 100 ECF patients (44 females, 56 males, mean age 54.1 years) were evaluated. Postoperative complications rate, readmission rate, length of hospital stay, prevalence of postoperative nausea and vomiting were assessed. Registered under ClinicalTrials.gov Identifier no. {"type":"clinical-trial","attrs":{"text":"NCT04771832","term_id":"NCT04771832"}}NCT04771832. Results: ERAS protocol was successfully introduced for ECF surgeries; however, eight modifications to the ERAS program was performed in 2015. They led to improvement of surgical outcomes: reduction of postoperative nausea and vomiting (15 vs. 17% patients, p = 0.025), overall complication rate (11 vs. 10, p = 0.021), median length of hospital stay (overall and after surgery, p = 0.022 and 0.002, respectively). Conclusions: ERAS protocol can be successfully used for ECF patients. Prescheduled audits can contribute to the improvement of care.     

The role of parenteral glutamine supplement for surgical patient perioperatively: result of a single center,prospective and controlled study

Background  We conducted a prospective and case-controlled study to evaluate the impact of supplement of alanyl-glutamine dipeptide (Gln) in parenteral nutrition on perioperative immune and nutritional changes and clinical outcomes for patients undergoing gastrointestinal (GI) operations. Materials and methods  During 2006, 70 patients undergoing GI surgeries were allocated equally into two groups. One group received regular parenteral nutrition and the other received the same formulation and supplemented with the Gln; the two groups were isonitrogenous. The infusion was started from 1 day before operation to the sixth day after operation for 7 days. Blood samples were collected on the morning of the day before the operation and on the morning 6 days after the operation and analyzed for immune and nutrition parameters. Results  There were no differences between the two groups in terms of clinical characteristics, operative procedures, biochemistry, nutritional status, and immune status preoperatively. After GI surgery, significant reduction in nutritional and immune parameters were observed in both groups, demonstrated by significant difference of albumin, C-reactive protein (CRP), lymphocyte count, T cell, and CD8 cell. The length of hospital stay is slightly longer in the control group patients, but not to statistical significance (16.3 ± 21.3 versus 12.2 ± 6.8 days, p = 0.299). In terms of morbidity, there was no difference between the two groups, but two patients in the control group had wound infection; none was noted in the Gln group (p = 1.0). No surgical mortality was noted in this study. Conclusions  Perioperative parenteral nutrition supplemented with Gln is beneficial for patients undergoing GI surgery. Gln supplementation significantly attenuated postoperative inflammation and ameliorated postoperative immunodepression as well as nutritional depression in GI surgery.     

Pharmacobezoars described and demystified

Introduction.?A bezoar is a concretion of foreign material that forms and persists in the gastrointestinal tract. Bezoars are classified by their material origins. Phytobezoars contain plant material, trichobezoars contain hair, lactobezoars contain milk proteins, and pharmacobezoars contain pharmaceutical products. Tablets, suspensions, and even insoluble drug delivery vehicles can, on rare occasions, and sometimes under specific circumstances, form pharmacobezoars. The goal of this review is to catalog and examine all of the available reports in the English language medical literature that convincingly describe the formation and management of pharmacobezoars. Methods.?Articles included in this review were identified by performing searches using the terms “bezoar,” “pharmacobezoar,” and “concretion” in the following databases: OVID MEDLINE, PubMed, and JSTOR. The complete MEDLINE and JSTOR holdings were included in the search without date ranges. The results were limited to English language publications. Articles that described nonmedication bezoars were not included in the review. Articles describing phytobezoars, food bezoars, fecal impactions, illicit drug packet ingestions, enteral feeding material bezoars, and hygroscopic diet aid bezoars were excluded. The bibliographic references within the articles already accumulated were then examined in order to gather additional pharmacobezoar cases. The cases are grouped by pharmaceutical agent that formed the bezoar, and groupings are arranged in alphabetical order. Discussions and conclusions specific to each pharmaceutical agent are included in that agent's subheading. Discussion.?Patterns and themes that emerged in the review of the assembled case reports are reviewed and presented in a more concise format. Conclusion.?Pharmacobezoars form under a wide variety of circumstances and in a wide variety of patients. They are difficult to diagnose reliably. Rules for suspecting, diagnosing, and properly managing a pharmacobezoar are highly dependent on the pharmaceutical agent or agents involved. Becoming familiar with the sparse data available on pharmacobezoars and maintaining a high index of suspicion in future clinical encounters may be the best way to improve diagnostic sensitivity and accuracy.