orlistat and Acute-Disease

The occurrence of acute lower limb ischemia (ALLI) is a serious risk within the context of aortic dissection repair. The aim of the present study was to examine the outcomes of patients with acute type A aortic dissection (ATAD) and concomitant lower extremity malperfusion.. We performed a retrospective medical record review at our tertiary referral center of patients who underwent ATAD repair from January 2002 to June 2018. We used univariate and multivariate analyses to compare the outcomes of patients with and without lower extremity malperfusion. The primary outcomes were 30-day and 1-year mortality.. A total of 378 patients underwent ATAD repair during the study period. Their mean age was 57 years, 68% were men, and 51% were White. A total of 62 patients (16%) presented with concomitant ALLI, including 35 (9%) who presented with isolated ALLI and 27 (7%) who presented with ALLI and concomitant malperfusion of at least one other organ. Of the 62 patients with ALLI, 46 underwent only proximal aortic repair. Of the 378 patients, 6 died within the first 24 hours, and their limb perfusion was not assessed. Among the 40 patients who underwent isolated proximal repair and survived >24 hours, 34 (85%) had resolution of their ALLI. Of the 16 patients who underwent concomitant lower extremity peripheral vascular procedures, 10 had bypass procedures and 1 died within 24 hours due to refractory coagulopathy and hypotension. All six patients with adequate follow-up imaging studies had asymptomatic occlusion of the bypass graft with recanalization of the occluded native arteries. Patients who presented with any organ malperfusion had increased 30-day (odds ratio, 1.8; P = .04) and 1-year (odds ratio, 1.8; P = .04) mortality and decreased overall survival (P < .01). For the patients with isolated ALLI, no significant differences were found in 30-day or 1-year mortality or overall survival (P = .57).. Proximal repair of ATAD resolves most cases of associated ALLI, and isolated ALLI does not affect short- or long-term survival. All patients with follow-up in our study who underwent extra-anatomic bypass developed asymptomatic graft occlusion, which could be attributed to competitive flow from the remodeled native arterial system. We believe that rapid and aggressive restoration of flow to the lower extremity is the best method to treat ALLI malperfusion syndrome. Close monitoring for the development of compartment syndrome is recommended.

Topics: Acute Disease; Aortic Dissection; Arterial Occlusive Diseases; Female; Humans; Ischemia; Lower Extremity; Male; Middle Aged; Orlistat; Peripheral Vascular Diseases; Retrospective Studies; Treatment Outcome

The study aimed to investigate the safety and efficacy of the Solitaire™ AB Stent System (ev3 Inc., Plymouth, MN, USA) for the treatment of acute lower extremity ischemia (ALLI) compared with conventional catheter-directed thrombolytic therapy.. Retrospective analysis of patients with ALLI treated in the Department of Interventional Radiology at the First Hospital of Nanjing from January 2017 to April 2020 divided into a conventional (CDT) group (. Of the 161 patients, 128 (79.5%) did not have a composite clinical outcome after 12 months of follow-up, namely, 78 CDT patients and 50 PMT patients, with significant differences in composite clinical outcome (26.4% vs. 9.1%,. PMT with the Solitaire™ AB Stent System is safer and more effective in treating patients with Rutherford stage I-IIB ALLI, with the advantage of rapid opening of obstructed vessels, shorter thrombolysis time, reduced thrombolytic dose, and improved blood flow to the infrapopliteal vessels.

Topics: Acute Disease; Arterial Occlusive Diseases; Catheters; Fibrinolytic Agents; Humans; Ischemia; Orlistat; Peripheral Vascular Diseases; Retrospective Studies; Stents; Thrombectomy; Thrombolytic Therapy; Treatment Outcome

Obesity is an important risk factor for severe acute pancreatitis. The necrosis of epididymal adipose tissue occurs in severe acute pancreatitis. Adipose tissue macrophages play an important role in metabolic related inflammation. Therefore, we explored the potential mechanisms between adipose tissue macrophages and obesity-related severe acute pancreatitis.. Severe acute pancreatitis mice model was induced by caerulein with lipopolysaccharide. The severity of severe acute pancreatitis was evaluated according to the morphological, general, and biochemical change. We assessed the injury of epididymal white adipose tissue, pancreas, and adipose tissue macrophages in obese mice and lean mice with severe acute pancreatitis. Outcomes of caerulein-induced severe acute pancreatitis were studied in lean and obese mice with or without lipase inhibitor orlistat.. Fat necrosis and pancreatic injury increased in the SAP groups. High levels of serum free fatty acid and triglyceride were increased significantly in the SAP group. The NLRP3-caspase1 inflammasome signal pathway in adipose tissue macrophages markedly enhanced in the SAP groups compared with control group. Free fatty acid can trigger macrophages inflammation through NLRP3-caspase1. Lipase inhibited by orlistat remarkably decreased in adipose tissue necrosis, and the levels of serum lipase, amylase, and pancreatic tissue damage decreased in the orlistat group compared with the SAP group. The NLRP3-caspase1 inflammasome pathway in adipose tissue macrophages markedly decreased in the orlistat groups compared with SAP group. The levels of serum free fatty acid and triglyceride were decreased significantly in the orlistat group.. Inflammation increases in adipose tissue macrophages of obese mice with severe acute pancreatitis. Free fatty acid generated via adipocyte lipolysis worsens inflammation in adipose tissue macrophages and the outcome of severe acute pancreatitis in obese mice through the NLRP3-caspase1 inflammasome pathway.

Topics: Acute Disease; Adipose Tissue; Animals; Caspase 1; Ceruletide; Fatty Acids, Nonesterified; Inflammasomes; Inflammation; Lipase; Macrophages; Mice; Necrosis; NLR Family, Pyrin Domain-Containing 3 Protein; Obesity; Orlistat; Pancreatitis; Triglycerides

Currently, there is no therapy for severe acute pancreatitis (AP) except for supportive care. The lipase inhibitor orlistat, the peroxisome proliferator-activated receptor γ agonist rosiglitazone, and the chemokine receptor 2 antagonists attenuate the severity of AP in rodents if administered before or at the time of induction of pancreatitis. However, it is unknown whether these treatments are effective if administered therapeutically after induction of pancreatitis.. Male C57BL6 mice with diet-induced obesity received 2 injections of mrIL-12 (150 ng per mouse) and mrIL-18 (750 ng per mouse) intraperitoneally at 24-hour intervals. The mice were injected 2, 24, and 48 hours after the second injection of IL-12 + IL-18 with orlistat (2 mg per mouse), rosiglitazone (0.4 mg per mouse), RS102895 (0.3 mg per mouse), or vehicle (20 μL of DMSO and 80 μL of canola oil) and euthanized after 72 hours.. Orlistat decreased intra-abdominal fat necrosis compared with vehicle (P < 0.05). However, none of the drug treatments produced significant decreases in pancreatic edema, acinar necrosis, or intrapancreatic fat necrosis.. Drugs previously shown to improve the severity of AP when given before or at the time of induction of pancreatitis failed to do so when administered therapeutically in the IL-12 + IL-18 model.

Topics: Acute Disease; Animals; Anti-Obesity Agents; Benzoxazines; Interleukin-12; Interleukin-18; Lactones; Male; Mice, Inbred C57BL; Obesity; Orlistat; Pancreatitis; Piperidines; Receptors, CCR2; Rosiglitazone; Severity of Illness Index; Thiazolidinediones; Treatment Failure; Vasodilator Agents

Orlistat is a pancreatic lipase inhibitor licensed for the treatment of obesity. As obesity rates increase and non-prescription dispensing of orlistat increases, an awareness of its adverse effects is of crucial importance as complications arise more frequently from increased use. Orlistat induced pancreatitis has been described only once previously, but without a diagnostic increase in serum amylase.. We report the case of two patients who developed severe acute abdominal pain and elevated pancreatic enzymes at 2 and 10 days after starting orlistat. In one case no alterative precipitant was identified. In the other, a predisposing history of pancreatic injury was present. In both cases all other contributory causes were excluded.. Our reports suggest orlistat can trigger drug induced acute pancreatitis in certain patients. For patients presenting with abdominal pain soon after commencing orlistat, a diagnosis of pancreatitis must be considered. We also recommend cautious use of orlistat in patients at risk of pancreatic injury.

Topics: Acute Disease; Aged; Anti-Obesity Agents; Female; Humans; Lactones; Middle Aged; Obesity; Orlistat; Pancreatitis

Topics: Acute Disease; Anti-Obesity Agents; Biopsy; Calcium Oxalate; Enzyme Inhibitors; Humans; Hyperoxaluria; Hyperoxaluria, Primary; Kidney; Kidney Cortex Necrosis; Lactones; Lipase; Orlistat; Retrospective Studies

Topics: Acute Disease; Anti-Obesity Agents; Female; Humans; Lactones; Middle Aged; Obesity; Orlistat; Pancreatitis

Orlistat is an oral inhibitor of gastrointestinal lipase used for weight reduction in obese patients. Although most adverse drug effects manifest in the gastrointestinal tract, this is the first reported case of orlistat-induced acute kidney injury secondary to acute oxalate nephropathy in a white woman with underlying chronic kidney disease. Acute kidney injury was associated temporally with an increased dose of orlistat and the development of increased fat malabsorption (more frequent loose oily stools). Urine sediment showed abundant calcium oxalate crystals and increased 24-hour urine oxalate concentration. Kidney biopsy showed deposition of calcium oxalate crystals within tubular lumens, consistent with acute oxalate nephropathy. Orlistat therapy was discontinued, and oral fluid intake was increased. A second kidney biopsy performed 1 month later to evaluate the slow resolution of kidney failure did not show calcium oxalate crystals within tubules. A steady improvement in renal function subsequently was observed. Results of a repeated 24-hour urine oxalate collection performed 3 weeks later when kidney function had improved were within normal limits.

Topics: Acute Disease; Calcium Oxalate; Enzyme Inhibitors; Female; Humans; Kidney Diseases; Lactones; Lipase; Middle Aged; Orlistat

Orlistat is an anti-obesity drug licensed in the United Kingdom for 7 years. We present a case of a patient who developed pancreatitis four days after commencing orlistat.. A 36 year old man presented to hospital with acute severe pancreatitis four days after starting a course of Orlistat, a lipase inhibitor used in the treatment of obesity. A diagnosis of drug related pancreatitis was made by exclusion of other causes of pancreatitis; he was a teetotaller, had a normal serum calcium, had no family history of pancreatitis or hyperlipidaemia, no history of trauma and had no evidence of gallstones on Computerised Tomography scan (CT).. Orlistat was the only drug that had been started recently and has been associated with pancreatitis previously. We found no case reports of similar cases, however 99 cases of orlistat related pancreatitis have been reported to the Food and Drug Administration (FDA), but no causative link has been found in clinical trials by the drug company. It is therefore not on the list of possible complications or side effects of the drug.

Topics: Abdominal Pain; Acute Disease; Adult; Amylases; Anti-Obesity Agents; Body Mass Index; C-Reactive Protein; Humans; L-Lactate Dehydrogenase; Lactones; Leukocyte Count; Male; Orlistat; Pancreatitis; Tomography, X-Ray Computed; Vomiting

Orlistat(Xenical(R), Roche) is considered a safe and effective drug to treat obesity by reduced absorption of 30% digested fat. To date, no serious adverse effects affecting the liver have been published except a case of subacute hepatic failure leading to liver transplantation in a young women with moderate obesity treated with orlistat. We report a case of acute cholestatic hepatitis in a young woman with moderate obesity treated with orlistat: a 33-year-old female admitted for the evaluation of jaundice. Abdominal ultrasonography, ERCP, routine chemistry, viral markers, and a fine needle biopsy of liver were performed. Microscopic findings of the liver biopsy specimen were compatible with acute cholestatic hepatitis. After steroid therapy, liver function was improved.

Topics: Acute Disease; Adult; Anti-Obesity Agents; Chemical and Drug Induced Liver Injury; Cholestasis; Female; Humans; Lactones; Lipase; Orlistat

Topics: Acute Disease; Anti-Obesity Agents; Chemical and Drug Induced Liver Injury; Diagnosis, Differential; Female; Humans; Lactones; Metabolic Clearance Rate; Middle Aged; Obesity, Morbid; Orlistat

Topics: Acute Disease; Cyclosporine; Enzyme Inhibitors; Graft Rejection; Humans; Lactones; Lipase; Orlistat