Outcomes of Surgical Management of Familial Intrahepatic Cholestasis 1 and Bile Salt Export Protein Deficiencies

Progressive familial intrahepatic cholestasis (PFIC) with normal circulating gamma-glutamyl transpeptidase levels can result from mutations in the ATP8B1 gene (encoding familial intrahepatic cholestasis 1 [FIC1] deficiency) or the ABCB11 gene (bile salt export protein [BSEP] deficiency). We investigated the outcomes of partial external biliary diversion, ileal exclusion, and liver transplantation in these two conditions. We conducted a retrospective multicenter study of 42 patients with FIC1 deficiency (FIC1 patients) and 60 patients with BSEP deficiency (BSEP patients) who had undergone one or more surgical procedures (57 diversions, 6 exclusions, and 57 transplants). For surgeries performed prior to transplantation, BSEP patients were divided into two groups, BSEP-common (bearing common missense mutations D482G or E297G, with likely residual function) and BSEP-other. We evaluated clinical and biochemical outcomes in these patients. Overall, diversion improved biochemical parameters, pruritus, and growth, with substantial variation in individual response. BSEP-common or FIC1 patients survived longer after diversion without developing cirrhosis, being listed for or undergoing liver transplantation, or dying, compared to BSEP-other patients. Transplantation resolved cholestasis in all groups. However, FIC1 patients commonly developed hepatic steatosis, diarrhea, and/or pancreatic disease after transplant accompanied by biochemical abnormalities and often had continued poor growth. In BSEP patients with impaired growth, this generally improved after transplantation. Conclusion: Diversion can improve clinical and biochemical status in FIC1 and BSEP deficiencies, but outcomes differ depending on genetic etiology. For many patients, particularly BSEP-other, diversion is not a permanent solution and transplantation is required. Although transplantation resolves cholestasis in patients with FIC1 and BSEP deficiencies, the overall outcome remains unsatisfactory in many FIC1 patients; this is mainly due to extrahepatic manifestations.Peer reviewe

Herbal Approaches to Pediatric Functional Abdominal Pain

Chronic abdominal pain is one of the most common problems seen by both pediatricians and pediatric gastroenterologists. Abdominal-pain-related functional gastrointestinal disorders (AP-FGIDs) are diagnosed in children with chronic and recurrent abdominal pain meeting clinical criteria set forth in the Rome IV criteria. AP-FGIDs affect approximately 20% of children worldwide and include functional dyspepsia (FD), irritable bowel syndrome (IBS), functional abdominal pain (FAP), and abdominal migraine. IBS accounts for 45% of pediatric AP-FGIDs. The pathophysiology of functional abdominal pain involves an interplay of factors including early life events, genetics, psychosocial influences, and physiologic factors of visceral sensitivity, motility disturbance, altered mucosal immune function, and altered central nervous system processing. Treatment approaches are varied and can include dietary, pharmacologic, and complementary medicine interventions, as well as psychosocial support, depending on the many aspects of the disorder and the needs of the individual patient. There is a strong interest in complementary and integrative medicine approaches to pediatric pain from both patients, providers, and families. In this article, we discuss popular herbal treatments typically used in the field of complementary medicine to treat pediatric AP-FGIDs: peppermint oil, Iberogast®, cannabis, fennel, and licorice. While high-quality data are rather limited, studies generally show that these remedies are at least as effective as placebo, and are well tolerated with minimal side effects. We will need more placebo-controlled, double-blind, and unbiased prospective studies to document and quantify efficacy

Differences in presentation and progression between severe FIC1 and BSEP deficiencies

Progressive familial intrahepatic cholestasis (PFIC) with normal serum levels of gamma-glutamyltranspeptidase can result from mutations in ATP8B1 (encoding familial intrahepatic cholestasis 1 [FIC1]) or ABCB11 (encoding bile salt export pump [BSEP]). We evaluated clinical and laboratory features of disease in patients diagnosed with PFIC, who carried mutations in ATP8B1 (FIC1 deficiency) or ABCB11 (BSEP deficiency). Our goal was to identify features that distinguish presentation and course of these two disorders, thus facilitating diagnosis and elucidating the differing consequences of ATP8B1 and ABCB11 mutations. A retrospective multi-center study was conducted, using questionnaires and chart review. Available clinical and biochemical data from 145 PFIC patients with mutations in either ATP8B1 (61 "FIC1 patients") or ABCB11 (84 "BSEP patients") were evaluated. At presentation, serum aminotransferase and bile salt levels were higher in BSEP patients; serum alkaline phosphatase values were higher, and serum albumin values were lower, in FIC1 patients. Elevated white blood cell counts, and giant or multinucleate cells at liver biopsy, were more common in BSEP patients. BSEP patients more often had gallstones and portal hypertension. Diarrhea, pancreatic disease, rickets, pneumonia, abnormal sweat tests, hearing impairment, and poor growth were more common in FIC1 patients. Among BSEP patients, the course of disease was less rapidly progressive in patients bearing the D482G mutation. Severe forms of FIC1 and BSEP deficiency differed. BSEP patients manifested more severe hepatobiliary disease, while FIC1 patients showed greater evidence of extrahepatic disease

Design of a clinical trial for the assessment cardioversion using Transesophageal Echocardiography (The ACUTE Multicenter Study)

Patients with atrial fibrillation (AF) undergoing cardioversion are at an increased risk of cardioembolic stroke and require anticoagulation, The Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) Multicenter Study is a randomized clinical trial of patients undergoing electrical cardioversion of AF of >2 days' duration comparing a transesophageal-guided strategy (TEE) with brief anticoagulation to the conventional anticoagulation strategy. patients randomly assigned to the TEE-guided strategy receive therapeutic anticoagulation before TEE and cardioversion, followed by 4 weeks of anticoagulation, Patients with thrombus imaged by TEE have postponement of cardioversion, continue anticoagulation for 3 weeks, and undergo a repeat TEE, Conventional strategy patients receive 3 weeks of anticoagulation before cardioversion, followed by 4 weeks of anticoagulation after cardioversion, The primary end point events are ischemic stroke, transient ischemic attack, and systemic embolization for an 8-week period from enrollment, Secondary end points are major and minor bleeding, all-cause mortality, successful return to and maintenance of sinus rhythm, and cost effectiveness, Analysis is based on the intention-to-treat principle. The anticipated rates of embolism of 2.9% for conventional strategy and 1.2% for the TEE-guided strategy are based on published research and the completed pilot study, The ACUTE Multicenter Study will randomize therapy and follow an estimated 3,000 patients from 65 study sites to determine the relative efficacy of the TEE-guided and conventional approaches to electrical cardioversion for patients in AF, The results of this investigation will have important clinical implications for the management of patients with AF undergoing electrical cardioversion. (C) 1998 by Excerpta Medica, Inc.Cleveland Clin Fdn, Dept Cardiol, Sect Cardiovasc Imaging, Cleveland, OH 44195 USAUniv Louisville, Louisville, KY 40292 USAUniv Nebraska, Omaha, NE 68182 USAWinthrop Univ Hosp, Mineola, NY 11501 USAEscorts Heart Inst & Res Ctr, New Delhi, IndiaCtr Med Caracas, Caracas, VenezuelaUniv Fed Sao Paulo, Sao Paulo, BrazilLancaster Heart Fdn, Lancaster, PA USAUniv Essen Gesamthsch, Essen, GermanyEl Azhar Univ, Cairo, EgyptSt Elisabeth Hosp, Tilburg, NetherlandsUniv Pittsburgh, Med Ctr, Pittsburgh, PA USARiverside Methodist Hosp, Columbus, OH 43214 USAUniv Rochester, Strong Mem Hosp, Rochester, NY 14642 USAUniv Calif San Francisco, San Francisco, CA 94143 USAUniv Massachusetts, Worcester, MA 01605 USAHosp Vera Cruz, Belo Horizonte, MG, BrazilHosp Socor, Belo Horizonte, MG, BrazilSaginaw Heart Grp, Saginaw, MI USAUniv Calif San Diego, San Diego, CA 92103 USANew England Med Ctr, Boston, MA 02111 USAWhite River Junction VA Med Ctr, White River Junction, VT USAUniv Cincinnati, Cincinnati, OH USAVet Affairs Med Ctr, Bronx, NY USAVirginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USAHarbor UCLA Med Ctr, Torrance, CA 90509 USAOsped Civile, Cento, ItalyUniv Chicago, Med Ctr, Chicago, IL 60637 USAUniv Texas, SW Med Ctr, Dallas, TX USAManly Hosp, Manly, NSW, AustraliaPrince Henry Hosp, Sydney, NSW, AustraliaN Shore Univ Hosp, Manhasset, NY USABaylor Coll Med, Methodist Hosp, Houston, TX 77030 USATexas Heart Inst, Houston, TX 77025 USAUniv New Mexico, Albuquerque, NM 87131 USARoyal Victoria Hosp, Montreal, PQ H3A 1A1, CanadaColumbia Cardiovasc Clin, Columbia, SC USAAustin Heart, Austin, TX USAOhio State Univ, Columbus, OH 43210 USAMed Coll Wisconsin, Froedtert Mem Lutheran Hosp, Milwaukee, WI 53226 USASt Nicholas Hosp, Milwaukee Cardiovasc Res, Milwaukee, WI USABlodgett Mem Med Ctr, Grand Rapids, MI USAClearwater Cardiovasc Consultants, Largo, FL USAN Cent Heart Fdn, Sioux Falls, SD USASentara Norfolk Gen Hosp, Norfolk, VA USALoma Linda VA Med Ctr, Loma Linda, CA USAMacNeal Ctr Clin Res, Berwyn, IL USATemple Univ Hosp, Philadelphia, PA 19140 USAHungarian Inst Cardiol, Budapest, HungaryBoston Univ, Boston, MA 02215 USABeth Israel Hosp, Boston, MA 02215 USAHosp Servidores Estado, Logoa, BrazilE Carolina Univ, Greenville, NC USAHartford Hosp, Hartford, CT 06115 USAGrad Hosp Philadelphia, Philadelphia, PA 19146 USASt Lukes Roosevelt Hosp, New York, NY 10025 USAAlton Ochsner Med Fdn & Ochsner Clin, New Orleans, LA 70121 USAEaston Hosp, Easton, PA USASt Johns Mercy Med Ctr, St Louis, MO 63141 USAMichigan Capital Med Ctr, Lansing, MI USAAlbany Med Coll, Albany, NY 12208 USAMontefiore Med Ctr, Bronx, NY 10467 USAUniv Kansas, Med Ctr, Kansas City, KS 66103 USAAndroscoggin Cardiol Associates, Auburn, ME USACleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USAEmory Univ, Sch Publ Hlth, Atlanta, GA USACleveland Clin Fdn, Dept Biostat, Cleveland, OH 44195 USACleveland Clin Fdn, Dept Vasc Med, Cleveland, OH 44195 USACleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USAUniv Fed Sao Paulo, Sao Paulo, BrazilWeb of Scienc